Clinicians have numerous pharmacotherapy options available to treat ADHD in their toolbox. How do you know which formulation or combination of therapies is right for your patient with ADHD?

According to Jeffrey R. Strawn, MD, the answer depends on onset and duration of the medication and how that fits in to the patient’s current needs.

The most common treatment for ADHD, stimulants, are amphetamine-based and methylphenidate-based compounds known for improving core symptoms of inattention, impulsivity, and hyperactivity and are “probably associated with the most efficacy relative to the other interventions,” Dr. Strawn, associate professor of psychiatry, pediatrics, and clinical pharmacology at Cincinnati Children’s Hospital Medical Center, said at Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “But what I think is also really important for us to remember as clinicians is that they improve adherence, social interactions, [and] academic efficiency as well as accuracy.”

Other ADHD pharmacotherapy options include nonstimulant norepinephrine reuptake inhibitors (NRIs) like atomoxetine, and alpha-2 agonists like the extended-release forms of guanfacine and clonidine. All are Food and Drug Administration–approved for the treatment of ADHD, and the FDA has approved some combination alpha-2 agonists and stimulants treatments for ADHD as well.

When making decisions about formulations for ADHD pharmacotherapy, clinicians should think about whether the patient has issues swallowing tablets or capsules. Tablets, capsules, and chewable tablets may be appropriate for patients who can easily take these medications, while patients who have problems with swallowing pills may benefit from dissolvable tablets, solutions, and transdermal applications. Each of these options “have differences in terms of absorption, also differences in terms of intestinal transit time in younger children, as well as patients perhaps with irritable bowel, as well as other conditions that may affect absorption,” Dr. Strawn said. Different formulations have unique considerations: liquid formulations have the benefit of making precise adjustments, sublingual formulations may have quick absorption and onset, and oral dissolvable tablets can improve treatment adherence and reduce misuse of medication.

Formulations can be available as a delayed release, extended release, pulsatile release, targeted release, or a combination of immediate, delayed, and/or extended release. “Ultimately, what this gives rise to is differences in onset of action and duration, as well as differences in the elimination profile of the medication,” he said.

Transdermal formulations “avoid the first-pass metabolism, which may reduce side effects or increase efficacy,” but patients converting from an oral formulation may require reducing the dose. “It’s always important to remember, for example, with something like Daytrana, the transdermal methylphenidate formulation, if we’re converting a patient from an oral methylphenidate, we roughly need to use half the dose for the transdermal formulation,” Dr. Strawn explained. Transdermal formulations can carry benefits of steady plasma concentrations and longer duration of action but may cause skin irritation or accidentally be removed. “It’s really important they’re properly disposed of because oftentimes they do contain some active medication within the residual matrix.”
 

Methylphenidate, mixed amphetamine salt–based preparations

Modified-release formulations include matrix- or reservoir-based formulations and are most importantly differentiated from other formulations by their gastrointestinal (GI) transit time and the permeation through the GI membrane. When considering what formulation to choose, “it’s important to consider that, even with an ‘extended release formulation,’ all of these medications have some percentage that is immediately released, and that percentage varies considerably from formulation to formulation,” Dr. Strawn said.

He noted that brand names are sometimes used for formulations “because it’s often very difficult for us as clinicians and even for pharmacists to distinguish between these various formulations of the medication, which often have the same ‘extended’ or ‘delayed release’ modifying term within the name of the medication.”

Examples of medications that have greater immediate release include Metadate CD (30%), Aptensio XR (37%), long-acting methylphenidate (50%), dexmethylphenidate extended-release (50%), and Mixed Salts amphetamine extended release (50%). Formulations with a less immediate release include Quillivant solution or Quillichew chewable tablets (20%), Dyanaval XR solution (20%), OROS methylphenidate (22%), Daytrana that begins within 1 or 2 hours and lasts for 9 hours, or lisdexamfetamine that begins within 1 hour and lasts for 9 hours.

Depending on a patient’s needs, one particular formulation may work better than another. Dexmethylphenidate (Focalin XR) has a 50% immediate release and 50% extended release formulation, which “may be really important for a high school student who has first period precalculus followed by second period human geography,” Dr. Strawn said, while “a patient who may have first period study hall and second period art” may benefit from OROS methylphenidate.

Clinicians should also consider the effect of counterclockwise hysteresis when adding a short-acting stimulant later in the day. “There seems to be something really magic about having that ascending concentration time curve that, when we’re on the descending loop of that concentration time curve, we really seem to get a dramatic waning of the effect of the medication, even though technically the concentration is within the ‘therapeutic range,’ ” Dr. Strawn said. “With counterclockwise hysteresis, we see that the effect increases with time for a given concentration of the medication.”
 

Combining ADHD pharmacotherapies

For children and adolescents with ADHD, atomoxetine is a nonstimulant, FDA-approved treatment option. “It seems to be effective not just in terms of total ADHD symptoms, but also in terms of hyperactive and impulsive symptoms as well as the inattentive symptoms,” Dr. Strawn said.

Pharmacogenetics can be a guide for selecting an atomoxetine for a patient with ADHD, he noted. “What I think is most relevant here is the way in which pharmacogenetics can actually help guide our dosing, which then optimizes tolerability, potentially efficacy of atomoxetine,” he said. “Atomoxetine is pretty extensively metabolized by [CYP]2D6, and it’s one of about 300 medications that actually has specific labeling from the FDA on dosing based on genotype. It recommends a slower titration, as well as a lower target dose of atomoxetine in individuals who are P450 2D6 poor metabolizers relative to those patients who are ultra-rapid or normal metabolizers.”

Atomoxetine is most often combined with methylphenidate and has some evidence of benefit in children or adolescents who do not have an adequate response to stimulants alone. When combining stimulants with the alpha-2 agonists guanfacine or clonidine, “there are some improvements in terms of the combination treatment relative to the monotherapy,” Dr. Strawn said. He also emphasized that patients taking guanfacine immediate release tend to have better absorption and faster onset, compared with the extended release formulation. “This is something that potentially is very important when we think beyond steady state and we think about the practical use of this medication,” he said.
 

Baseline history is important

Overall, taking a baseline history of a patient with ADHD is “critically important” before starting them on stimulants, Dr. Strawn said. “Specifically, I would recommend documenting a negative history of syncope, family history of sudden cardiac death, as well as the lack of any known history of structural cardiac abnormalities,” he said. “Without a consultation with the cardiologist specifically around this question, I’m very, very, very hesitant – as in I don’t – use stimulants in patients who have histories of aortic stenosis, Wolff-Parkinson-White, as well as arrhythmogenic right ventricular dysplasia.”

Although patients with ADHD were typically followed with routine hemodynamic monitoring every 3 months prior to the COVID-19 pandemic, some clinicians see their patients with ADHD less frequently if they have been stabilized on a stimulant. “It is important to check not just with the patient, but also with parents and teachers as we’re adjusting medication dose and trying to optimize the treatment regimen, particularly in young children. In adults, it may also be very helpful to talk with spouses,” Dr. Strawn said.

Dr. Strawn also called attention to a recommendation to perform a routine electrocardiogram (EKG) in patients with ADHD who might receive stimulants. “At present, there is no recommendation to obtain a routine screening EKG in these patients, provided that we have an absence of those other red flags on the history,” he said. “Certainly, I would consider it in situations where I do have persistent tachycardia or hypertension, or there are other treatment-emergent symptoms, although really in many of these situations, I’m actually speaking on the phone with my pediatric or adult cardiology colleagues.”

Global Academy and this news organization are owned by the same parent company. Dr. Strawn reported receiving research support from Allergan, the FDA, the National Institutes of Health, Neuronetics, and Otsuka; serving as a consultant and receiving material support from Myriad; receiving royalties from Springer Publishing; and serving as a consultant for Intra-Cellular Therapies. In addition, he has been on the speaker’s bureau for the Neuroscience Education Institute and CMEology, and Medscape.

Clinicians have numerous pharmacotherapy options available to treat ADHD in their toolbox. How do you know which formulation or combination of therapies is right for your patient with ADHD?

According to Jeffrey R. Strawn, MD, the answer depends on onset and duration of the medication and how that fits in to the patient’s current needs.

The most common treatment for ADHD, stimulants, are amphetamine-based and methylphenidate-based compounds known for improving core symptoms of inattention, impulsivity, and hyperactivity and are “probably associated with the most efficacy relative to the other interventions,” Dr. Strawn, associate professor of psychiatry, pediatrics, and clinical pharmacology at Cincinnati Children’s Hospital Medical Center, said at Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “But what I think is also really important for us to remember as clinicians is that they improve adherence, social interactions, [and] academic efficiency as well as accuracy.”

Other ADHD pharmacotherapy options include nonstimulant norepinephrine reuptake inhibitors (NRIs) like atomoxetine, and alpha-2 agonists like the extended-release forms of guanfacine and clonidine. All are Food and Drug Administration–approved for the treatment of ADHD, and the FDA has approved some combination alpha-2 agonists and stimulants treatments for ADHD as well.

When making decisions about formulations for ADHD pharmacotherapy, clinicians should think about whether the patient has issues swallowing tablets or capsules. Tablets, capsules, and chewable tablets may be appropriate for patients who can easily take these medications, while patients who have problems with swallowing pills may benefit from dissolvable tablets, solutions, and transdermal applications. Each of these options “have differences in terms of absorption, also differences in terms of intestinal transit time in younger children, as well as patients perhaps with irritable bowel, as well as other conditions that may affect absorption,” Dr. Strawn said. Different formulations have unique considerations: liquid formulations have the benefit of making precise adjustments, sublingual formulations may have quick absorption and onset, and oral dissolvable tablets can improve treatment adherence and reduce misuse of medication.

Formulations can be available as a delayed release, extended release, pulsatile release, targeted release, or a combination of immediate, delayed, and/or extended release. “Ultimately, what this gives rise to is differences in onset of action and duration, as well as differences in the elimination profile of the medication,” he said.

Transdermal formulations “avoid the first-pass metabolism, which may reduce side effects or increase efficacy,” but patients converting from an oral formulation may require reducing the dose. “It’s always important to remember, for example, with something like Daytrana, the transdermal methylphenidate formulation, if we’re converting a patient from an oral methylphenidate, we roughly need to use half the dose for the transdermal formulation,” Dr. Strawn explained. Transdermal formulations can carry benefits of steady plasma concentrations and longer duration of action but may cause skin irritation or accidentally be removed. “It’s really important they’re properly disposed of because oftentimes they do contain some active medication within the residual matrix.”
 

Methylphenidate, mixed amphetamine salt–based preparations

Modified-release formulations include matrix- or reservoir-based formulations and are most importantly differentiated from other formulations by their gastrointestinal (GI) transit time and the permeation through the GI membrane. When considering what formulation to choose, “it’s important to consider that, even with an ‘extended release formulation,’ all of these medications have some percentage that is immediately released, and that percentage varies considerably from formulation to formulation,” Dr. Strawn said.

He noted that brand names are sometimes used for formulations “because it’s often very difficult for us as clinicians and even for pharmacists to distinguish between these various formulations of the medication, which often have the same ‘extended’ or ‘delayed release’ modifying term within the name of the medication.”

Examples of medications that have greater immediate release include Metadate CD (30%), Aptensio XR (37%), long-acting methylphenidate (50%), dexmethylphenidate extended-release (50%), and Mixed Salts amphetamine extended release (50%). Formulations with a less immediate release include Quillivant solution or Quillichew chewable tablets (20%), Dyanaval XR solution (20%), OROS methylphenidate (22%), Daytrana that begins within 1 or 2 hours and lasts for 9 hours, or lisdexamfetamine that begins within 1 hour and lasts for 9 hours.

Depending on a patient’s needs, one particular formulation may work better than another. Dexmethylphenidate (Focalin XR) has a 50% immediate release and 50% extended release formulation, which “may be really important for a high school student who has first period precalculus followed by second period human geography,” Dr. Strawn said, while “a patient who may have first period study hall and second period art” may benefit from OROS methylphenidate.

Clinicians should also consider the effect of counterclockwise hysteresis when adding a short-acting stimulant later in the day. “There seems to be something really magic about having that ascending concentration time curve that, when we’re on the descending loop of that concentration time curve, we really seem to get a dramatic waning of the effect of the medication, even though technically the concentration is within the ‘therapeutic range,’ ” Dr. Strawn said. “With counterclockwise hysteresis, we see that the effect increases with time for a given concentration of the medication.”
 

Combining ADHD pharmacotherapies

For children and adolescents with ADHD, atomoxetine is a nonstimulant, FDA-approved treatment option. “It seems to be effective not just in terms of total ADHD symptoms, but also in terms of hyperactive and impulsive symptoms as well as the inattentive symptoms,” Dr. Strawn said.

Pharmacogenetics can be a guide for selecting an atomoxetine for a patient with ADHD, he noted. “What I think is most relevant here is the way in which pharmacogenetics can actually help guide our dosing, which then optimizes tolerability, potentially efficacy of atomoxetine,” he said. “Atomoxetine is pretty extensively metabolized by [CYP]2D6, and it’s one of about 300 medications that actually has specific labeling from the FDA on dosing based on genotype. It recommends a slower titration, as well as a lower target dose of atomoxetine in individuals who are P450 2D6 poor metabolizers relative to those patients who are ultra-rapid or normal metabolizers.”

Atomoxetine is most often combined with methylphenidate and has some evidence of benefit in children or adolescents who do not have an adequate response to stimulants alone. When combining stimulants with the alpha-2 agonists guanfacine or clonidine, “there are some improvements in terms of the combination treatment relative to the monotherapy,” Dr. Strawn said. He also emphasized that patients taking guanfacine immediate release tend to have better absorption and faster onset, compared with the extended release formulation. “This is something that potentially is very important when we think beyond steady state and we think about the practical use of this medication,” he said.
 

Baseline history is important

Overall, taking a baseline history of a patient with ADHD is “critically important” before starting them on stimulants, Dr. Strawn said. “Specifically, I would recommend documenting a negative history of syncope, family history of sudden cardiac death, as well as the lack of any known history of structural cardiac abnormalities,” he said. “Without a consultation with the cardiologist specifically around this question, I’m very, very, very hesitant – as in I don’t – use stimulants in patients who have histories of aortic stenosis, Wolff-Parkinson-White, as well as arrhythmogenic right ventricular dysplasia.”

Although patients with ADHD were typically followed with routine hemodynamic monitoring every 3 months prior to the COVID-19 pandemic, some clinicians see their patients with ADHD less frequently if they have been stabilized on a stimulant. “It is important to check not just with the patient, but also with parents and teachers as we’re adjusting medication dose and trying to optimize the treatment regimen, particularly in young children. In adults, it may also be very helpful to talk with spouses,” Dr. Strawn said.

Dr. Strawn also called attention to a recommendation to perform a routine electrocardiogram (EKG) in patients with ADHD who might receive stimulants. “At present, there is no recommendation to obtain a routine screening EKG in these patients, provided that we have an absence of those other red flags on the history,” he said. “Certainly, I would consider it in situations where I do have persistent tachycardia or hypertension, or there are other treatment-emergent symptoms, although really in many of these situations, I’m actually speaking on the phone with my pediatric or adult cardiology colleagues.”

Global Academy and this news organization are owned by the same parent company. Dr. Strawn reported receiving research support from Allergan, the FDA, the National Institutes of Health, Neuronetics, and Otsuka; serving as a consultant and receiving material support from Myriad; receiving royalties from Springer Publishing; and serving as a consultant for Intra-Cellular Therapies. In addition, he has been on the speaker’s bureau for the Neuroscience Education Institute and CMEology, and Medscape.

Clinicians have numerous pharmacotherapy options available to treat ADHD in their toolbox. How do you know which formulation or combination of therapies is right for your patient with ADHD?

According to Jeffrey R. Strawn, MD, the answer depends on onset and duration of the medication and how that fits in to the patient’s current needs.

The most common treatment for ADHD, stimulants, are amphetamine-based and methylphenidate-based compounds known for improving core symptoms of inattention, impulsivity, and hyperactivity and are “probably associated with the most efficacy relative to the other interventions,” Dr. Strawn, associate professor of psychiatry, pediatrics, and clinical pharmacology at Cincinnati Children’s Hospital Medical Center, said at Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “But what I think is also really important for us to remember as clinicians is that they improve adherence, social interactions, [and] academic efficiency as well as accuracy.”

Other ADHD pharmacotherapy options include nonstimulant norepinephrine reuptake inhibitors (NRIs) like atomoxetine, and alpha-2 agonists like the extended-release forms of guanfacine and clonidine. All are Food and Drug Administration–approved for the treatment of ADHD, and the FDA has approved some combination alpha-2 agonists and stimulants treatments for ADHD as well.

When making decisions about formulations for ADHD pharmacotherapy, clinicians should think about whether the patient has issues swallowing tablets or capsules. Tablets, capsules, and chewable tablets may be appropriate for patients who can easily take these medications, while patients who have problems with swallowing pills may benefit from dissolvable tablets, solutions, and transdermal applications. Each of these options “have differences in terms of absorption, also differences in terms of intestinal transit time in younger children, as well as patients perhaps with irritable bowel, as well as other conditions that may affect absorption,” Dr. Strawn said. Different formulations have unique considerations: liquid formulations have the benefit of making precise adjustments, sublingual formulations may have quick absorption and onset, and oral dissolvable tablets can improve treatment adherence and reduce misuse of medication.

Formulations can be available as a delayed release, extended release, pulsatile release, targeted release, or a combination of immediate, delayed, and/or extended release. “Ultimately, what this gives rise to is differences in onset of action and duration, as well as differences in the elimination profile of the medication,” he said.

Transdermal formulations “avoid the first-pass metabolism, which may reduce side effects or increase efficacy,” but patients converting from an oral formulation may require reducing the dose. “It’s always important to remember, for example, with something like Daytrana, the transdermal methylphenidate formulation, if we’re converting a patient from an oral methylphenidate, we roughly need to use half the dose for the transdermal formulation,” Dr. Strawn explained. Transdermal formulations can carry benefits of steady plasma concentrations and longer duration of action but may cause skin irritation or accidentally be removed. “It’s really important they’re properly disposed of because oftentimes they do contain some active medication within the residual matrix.”
 

Methylphenidate, mixed amphetamine salt–based preparations

Modified-release formulations include matrix- or reservoir-based formulations and are most importantly differentiated from other formulations by their gastrointestinal (GI) transit time and the permeation through the GI membrane. When considering what formulation to choose, “it’s important to consider that, even with an ‘extended release formulation,’ all of these medications have some percentage that is immediately released, and that percentage varies considerably from formulation to formulation,” Dr. Strawn said.

He noted that brand names are sometimes used for formulations “because it’s often very difficult for us as clinicians and even for pharmacists to distinguish between these various formulations of the medication, which often have the same ‘extended’ or ‘delayed release’ modifying term within the name of the medication.”

Examples of medications that have greater immediate release include Metadate CD (30%), Aptensio XR (37%), long-acting methylphenidate (50%), dexmethylphenidate extended-release (50%), and Mixed Salts amphetamine extended release (50%). Formulations with a less immediate release include Quillivant solution or Quillichew chewable tablets (20%), Dyanaval XR solution (20%), OROS methylphenidate (22%), Daytrana that begins within 1 or 2 hours and lasts for 9 hours, or lisdexamfetamine that begins within 1 hour and lasts for 9 hours.

Depending on a patient’s needs, one particular formulation may work better than another. Dexmethylphenidate (Focalin XR) has a 50% immediate release and 50% extended release formulation, which “may be really important for a high school student who has first period precalculus followed by second period human geography,” Dr. Strawn said, while “a patient who may have first period study hall and second period art” may benefit from OROS methylphenidate.

Clinicians should also consider the effect of counterclockwise hysteresis when adding a short-acting stimulant later in the day. “There seems to be something really magic about having that ascending concentration time curve that, when we’re on the descending loop of that concentration time curve, we really seem to get a dramatic waning of the effect of the medication, even though technically the concentration is within the ‘therapeutic range,’ ” Dr. Strawn said. “With counterclockwise hysteresis, we see that the effect increases with time for a given concentration of the medication.”
 

Combining ADHD pharmacotherapies

For children and adolescents with ADHD, atomoxetine is a nonstimulant, FDA-approved treatment option. “It seems to be effective not just in terms of total ADHD symptoms, but also in terms of hyperactive and impulsive symptoms as well as the inattentive symptoms,” Dr. Strawn said.

Pharmacogenetics can be a guide for selecting an atomoxetine for a patient with ADHD, he noted. “What I think is most relevant here is the way in which pharmacogenetics can actually help guide our dosing, which then optimizes tolerability, potentially efficacy of atomoxetine,” he said. “Atomoxetine is pretty extensively metabolized by [CYP]2D6, and it’s one of about 300 medications that actually has specific labeling from the FDA on dosing based on genotype. It recommends a slower titration, as well as a lower target dose of atomoxetine in individuals who are P450 2D6 poor metabolizers relative to those patients who are ultra-rapid or normal metabolizers.”

Atomoxetine is most often combined with methylphenidate and has some evidence of benefit in children or adolescents who do not have an adequate response to stimulants alone. When combining stimulants with the alpha-2 agonists guanfacine or clonidine, “there are some improvements in terms of the combination treatment relative to the monotherapy,” Dr. Strawn said. He also emphasized that patients taking guanfacine immediate release tend to have better absorption and faster onset, compared with the extended release formulation. “This is something that potentially is very important when we think beyond steady state and we think about the practical use of this medication,” he said.
 

Baseline history is important

Overall, taking a baseline history of a patient with ADHD is “critically important” before starting them on stimulants, Dr. Strawn said. “Specifically, I would recommend documenting a negative history of syncope, family history of sudden cardiac death, as well as the lack of any known history of structural cardiac abnormalities,” he said. “Without a consultation with the cardiologist specifically around this question, I’m very, very, very hesitant – as in I don’t – use stimulants in patients who have histories of aortic stenosis, Wolff-Parkinson-White, as well as arrhythmogenic right ventricular dysplasia.”

Although patients with ADHD were typically followed with routine hemodynamic monitoring every 3 months prior to the COVID-19 pandemic, some clinicians see their patients with ADHD less frequently if they have been stabilized on a stimulant. “It is important to check not just with the patient, but also with parents and teachers as we’re adjusting medication dose and trying to optimize the treatment regimen, particularly in young children. In adults, it may also be very helpful to talk with spouses,” Dr. Strawn said.

Dr. Strawn also called attention to a recommendation to perform a routine electrocardiogram (EKG) in patients with ADHD who might receive stimulants. “At present, there is no recommendation to obtain a routine screening EKG in these patients, provided that we have an absence of those other red flags on the history,” he said. “Certainly, I would consider it in situations where I do have persistent tachycardia or hypertension, or there are other treatment-emergent symptoms, although really in many of these situations, I’m actually speaking on the phone with my pediatric or adult cardiology colleagues.”

Global Academy and this news organization are owned by the same parent company. Dr. Strawn reported receiving research support from Allergan, the FDA, the National Institutes of Health, Neuronetics, and Otsuka; serving as a consultant and receiving material support from Myriad; receiving royalties from Springer Publishing; and serving as a consultant for Intra-Cellular Therapies. In addition, he has been on the speaker’s bureau for the Neuroscience Education Institute and CMEology, and Medscape.

When there is an abnormality in the pituitary gland, many potential areas could be affected because of the extent and range of hormones produced by the “master gland,” Ashlyn Smith, PA-C, of Endocrinology Associates, Scottsdale, Ariz., said in a presentation at the at the virtual meeting of the annual Metabolic and Endocrine Disease Summit held by Global Academy for Medical Education.

The most common demographic for pituitary disorders is women in their 30s and 40s, Ms. Smith said. Early red flags for pituitary problems include patients presenting with headaches and/or blurred or double vision, which could signal bitemporal hemianopsia, she said.

Roughly two-thirds of pituitary adenomas are functional, meaning that they secrete pituitary hormones and cause clinical syndromes, Ms. Smith said. The most common reason for hypersecretion is hyperprolactinemia, she said.

Hyperprolactinemia, like most pituitary conditions, is more common in women than men, Ms. Smith noted. However, symptoms may include not only galactorrhea, but also gynecomastia, and hypogonadism, which may be red flags in men, she noted.

“Prolactin inhibits the gonadal pathway, so we see low gonadal hormones. For example, if men present with atypical hypogonadism for their age, or women present with changes in the menstrual cycle, check the prolactin levels,” she said.

The etiologies of hyperprolactinemia include physiologic reasons such as breastfeeding and pregnancy, as well as intercourse and breast manipulation, stress, and sleep issues. Pathologic reasons for prolactin elevation include prolactinoma, gonad-hormone secreting tumor, hypothyroidism, and renal insufficiency, Ms. Smith said.

Evaluation of patients with suspected hyperprolactinemia includes screening for physiologic causes, renal function and thyroid function tests, and a thyroid-specific MRI. Ordering a dedicated MRI of the pituitary gland is important to help identify compression of the optic nerve, noted Ms. Smith.

A medication review also is essential in evaluating hyperprolactinemia, and especially in the setting of the COVID-19 pandemic, because patients may have made changes to psychiatric medications, said Ms. Smith. Neuroleptics and antipsychotics including risperidone, haloperidol, chlorpromazine, and thiothixene can be associated with hyperprolactinemia, as can benzodiazepines and various analgesics and antidepressants, she said.

Treatment in cases of medication-induced hyperprolactinemia can be challenging if the patients are unable to change a medication, said Ms. Smith. However, patients with hypogonadism or low bone mineral density who can’t change medications may benefit from exogenous gonadal hormones, she said.

Some patients with hyperprolactinemia benefit from treatment with dopamine agonists, which may ease symptoms and reduce the size of the prolactinoma, she explained. However, patients on dopamine agonists should be alert to side effects including constipation and orthostasis. Ms. Smith said she recommends that patients on dopamine agonists for hyperprolactinemia take the medication at night so they are lying down if orthostasis occurs.

Monitor prolactin levels at 1 month, and taper or discontinue if the prolactin returns to normal and the adenoma resolves, which can take approximately 2 years, she said. Ms. Smith then advised follow-up every 3 months for 1 year, then annual prolactin checks.

The risk of recurrence ranges from 26% to 69%, Ms. Smith said, and is higher in patients with higher prolactin levels and larger adenomas, she noted. Recurrence is most likely within a year of withdrawal from treatment, she said.

Ms. Smith disclosed serving as an adviser and speaker for Abbott Nutrition, a speaker for Xeris Pharmaceuticals, and an adviser for Sanofi and Radius.

Global Academy for Medical Education and this news organization are owned by the same parent company.

SOURCE: Smith A. MEDS 2020.

When there is an abnormality in the pituitary gland, many potential areas could be affected because of the extent and range of hormones produced by the “master gland,” Ashlyn Smith, PA-C, of Endocrinology Associates, Scottsdale, Ariz., said in a presentation at the at the virtual meeting of the annual Metabolic and Endocrine Disease Summit held by Global Academy for Medical Education.

The most common demographic for pituitary disorders is women in their 30s and 40s, Ms. Smith said. Early red flags for pituitary problems include patients presenting with headaches and/or blurred or double vision, which could signal bitemporal hemianopsia, she said.

Roughly two-thirds of pituitary adenomas are functional, meaning that they secrete pituitary hormones and cause clinical syndromes, Ms. Smith said. The most common reason for hypersecretion is hyperprolactinemia, she said.

Hyperprolactinemia, like most pituitary conditions, is more common in women than men, Ms. Smith noted. However, symptoms may include not only galactorrhea, but also gynecomastia, and hypogonadism, which may be red flags in men, she noted.

“Prolactin inhibits the gonadal pathway, so we see low gonadal hormones. For example, if men present with atypical hypogonadism for their age, or women present with changes in the menstrual cycle, check the prolactin levels,” she said.

The etiologies of hyperprolactinemia include physiologic reasons such as breastfeeding and pregnancy, as well as intercourse and breast manipulation, stress, and sleep issues. Pathologic reasons for prolactin elevation include prolactinoma, gonad-hormone secreting tumor, hypothyroidism, and renal insufficiency, Ms. Smith said.

Evaluation of patients with suspected hyperprolactinemia includes screening for physiologic causes, renal function and thyroid function tests, and a thyroid-specific MRI. Ordering a dedicated MRI of the pituitary gland is important to help identify compression of the optic nerve, noted Ms. Smith.

A medication review also is essential in evaluating hyperprolactinemia, and especially in the setting of the COVID-19 pandemic, because patients may have made changes to psychiatric medications, said Ms. Smith. Neuroleptics and antipsychotics including risperidone, haloperidol, chlorpromazine, and thiothixene can be associated with hyperprolactinemia, as can benzodiazepines and various analgesics and antidepressants, she said.

Treatment in cases of medication-induced hyperprolactinemia can be challenging if the patients are unable to change a medication, said Ms. Smith. However, patients with hypogonadism or low bone mineral density who can’t change medications may benefit from exogenous gonadal hormones, she said.

Some patients with hyperprolactinemia benefit from treatment with dopamine agonists, which may ease symptoms and reduce the size of the prolactinoma, she explained. However, patients on dopamine agonists should be alert to side effects including constipation and orthostasis. Ms. Smith said she recommends that patients on dopamine agonists for hyperprolactinemia take the medication at night so they are lying down if orthostasis occurs.

Monitor prolactin levels at 1 month, and taper or discontinue if the prolactin returns to normal and the adenoma resolves, which can take approximately 2 years, she said. Ms. Smith then advised follow-up every 3 months for 1 year, then annual prolactin checks.

The risk of recurrence ranges from 26% to 69%, Ms. Smith said, and is higher in patients with higher prolactin levels and larger adenomas, she noted. Recurrence is most likely within a year of withdrawal from treatment, she said.

Ms. Smith disclosed serving as an adviser and speaker for Abbott Nutrition, a speaker for Xeris Pharmaceuticals, and an adviser for Sanofi and Radius.

Global Academy for Medical Education and this news organization are owned by the same parent company.

SOURCE: Smith A. MEDS 2020.

When there is an abnormality in the pituitary gland, many potential areas could be affected because of the extent and range of hormones produced by the “master gland,” Ashlyn Smith, PA-C, of Endocrinology Associates, Scottsdale, Ariz., said in a presentation at the at the virtual meeting of the annual Metabolic and Endocrine Disease Summit held by Global Academy for Medical Education.

The most common demographic for pituitary disorders is women in their 30s and 40s, Ms. Smith said. Early red flags for pituitary problems include patients presenting with headaches and/or blurred or double vision, which could signal bitemporal hemianopsia, she said.

Roughly two-thirds of pituitary adenomas are functional, meaning that they secrete pituitary hormones and cause clinical syndromes, Ms. Smith said. The most common reason for hypersecretion is hyperprolactinemia, she said.

Hyperprolactinemia, like most pituitary conditions, is more common in women than men, Ms. Smith noted. However, symptoms may include not only galactorrhea, but also gynecomastia, and hypogonadism, which may be red flags in men, she noted.

“Prolactin inhibits the gonadal pathway, so we see low gonadal hormones. For example, if men present with atypical hypogonadism for their age, or women present with changes in the menstrual cycle, check the prolactin levels,” she said.

The etiologies of hyperprolactinemia include physiologic reasons such as breastfeeding and pregnancy, as well as intercourse and breast manipulation, stress, and sleep issues. Pathologic reasons for prolactin elevation include prolactinoma, gonad-hormone secreting tumor, hypothyroidism, and renal insufficiency, Ms. Smith said.

Evaluation of patients with suspected hyperprolactinemia includes screening for physiologic causes, renal function and thyroid function tests, and a thyroid-specific MRI. Ordering a dedicated MRI of the pituitary gland is important to help identify compression of the optic nerve, noted Ms. Smith.

A medication review also is essential in evaluating hyperprolactinemia, and especially in the setting of the COVID-19 pandemic, because patients may have made changes to psychiatric medications, said Ms. Smith. Neuroleptics and antipsychotics including risperidone, haloperidol, chlorpromazine, and thiothixene can be associated with hyperprolactinemia, as can benzodiazepines and various analgesics and antidepressants, she said.

Treatment in cases of medication-induced hyperprolactinemia can be challenging if the patients are unable to change a medication, said Ms. Smith. However, patients with hypogonadism or low bone mineral density who can’t change medications may benefit from exogenous gonadal hormones, she said.

Some patients with hyperprolactinemia benefit from treatment with dopamine agonists, which may ease symptoms and reduce the size of the prolactinoma, she explained. However, patients on dopamine agonists should be alert to side effects including constipation and orthostasis. Ms. Smith said she recommends that patients on dopamine agonists for hyperprolactinemia take the medication at night so they are lying down if orthostasis occurs.

Monitor prolactin levels at 1 month, and taper or discontinue if the prolactin returns to normal and the adenoma resolves, which can take approximately 2 years, she said. Ms. Smith then advised follow-up every 3 months for 1 year, then annual prolactin checks.

The risk of recurrence ranges from 26% to 69%, Ms. Smith said, and is higher in patients with higher prolactin levels and larger adenomas, she noted. Recurrence is most likely within a year of withdrawal from treatment, she said.

Ms. Smith disclosed serving as an adviser and speaker for Abbott Nutrition, a speaker for Xeris Pharmaceuticals, and an adviser for Sanofi and Radius.

Global Academy for Medical Education and this news organization are owned by the same parent company.

SOURCE: Smith A. MEDS 2020.

Over the past 4 decades there has been increasing use of minimally invasive surgery (MIS) for gynecologic cancer, particularly endometrial and cervical cancers. Uterine manipulators are a device inserted into the uterine cavity during MIS approaches to aid in directing the uterus within the pelvis, facilitating access to the uterine blood supply, defining the cardinal ligaments, lateralizing the ureters, and delineating the cervicovaginal junction. However, concerns have been raised regarding whether these devices are safe to use when the uterine corpus or cervix contains cancer.

In 2018, the LACC trial was published and demonstrated decreased survival for patients with cervical cancer who had undergone radical hysterectomy via a minimally invasive route.¹ Several hypotheses were proposed to explain this finding including possible tumor disruption from use of a uterine manipulator. Regrettably, this study did not document manipulator use, and therefore its influence on outcomes could not be measured. However, since that time there has been honed interest into the potential negative influence of uterine manipulators on endometrial and cervical cancer surgery.

Uterine manipulators typically are inserted through the uterine cervix and reside in the endometrial cavity. It is often an inflated balloon which stabilizes the device within the cavity. Hypotheses for how they may contribute to the spread of malignancy include the massage of endometrial tumor from the pressure of the inflated balloon, facilitation of tumor dissemination through cervical lymphatics or vasculature as the manipulator traverses or punctures a cervical cancer, and possibly perforation of the uterine cavity during placement of the manipulator, and in doing so, contaminating the peritoneal cavity with endometrial or cervical cancer cells that have been dragged through with the device.

Interestingly, uterine manipulator placement is not the only time during which endometrial or cervical cancers may be disturbed prior to resection. Many diagnostic procedures such as cervical excisional procedures (loop electrosurgical excision procedure and conizations) or hysteroscopic resections cause significant intentional disruption of tumor. In the case of hysteroscopy for endometrial cancer, endometrial cancer cells have been detected in the peritoneal washings of endometrial cancer patients who have undergone this procedure, however, no worse outcomes have been associated when hysteroscopy was included as part of the diagnostic work-up, suggesting that more than simply efflux into the peritoneal cavity is necessary for those tumor cells to have metastatic potential.²

Indeed the data is mixed regarding oncologic outcomes with uterine manipulator use, especially for endometrial cancer. In one recent study the outcomes of 951 patients with endometrial cancer from seven Italian centers were evaluated.³ There was no difference in recurrence rates or disease-specific survival between the 579 patients in whom manipulators were used and the 372 patients in which surgery was performed without manipulators. More recently a Spanish study reported retrospectively on 2,661 patients at 15 centers and determined that use of a uterine manipulator (two-thirds of the cohort) was associated with a hazard ratio of 1.74 (95% confidence interval, 1.07-2.83) for risk of death.⁴ Unfortunately, in this study there were substantial differences between sites that used manipulators and those that did not. Additionally, while one would expect different patterns of recurrence if the manipulator was introducing a unique mechanism for metastasis, this was not observed between the manipulator and nonmanipulator arms. Finally, the groups were intrinsically different with respect to important risk factors such as lymphovascular space invasion, which might have contributed to the observed outcomes. It is important to recognize that, in both the LAP-2 and LACE trials, minimally invasive hysterectomy for endometrial cancer had been shown to have noninferior survival outcomes, compared with open hysterectomy.^5,6 While these large randomized, controlled trials did not capture uterine manipulator usage, presumably it was utilized in at least some or most cases, and without apparent significant negative effect.

In cervical cancer, there is more competing data raising concern regarding manipulator use. The SUCCOR study was completed in 2020 and included a retrospective evaluation of 1,272 patients who had undergone open or MIS radical hysterectomy for early stage cervical cancer across 126 European centers during 2013-2014.⁷ They were able to evaluate for variables, such as uterine manipulator use. While they found that recurrence was higher for patients who had MIS hysterectomy, the HR (2.07) was similar to the HR for recurrence (2.76) among those who had uterine manipulator use. Conversely, the hazard ratio for recurrence following MIS radical hysterectomy without a manipulator was comparable with the superior rates seen with open surgery. This study was retrospective and therefore is largely hypothesis generating, however it does raise the question of whether the technique of MIS radical hysterectomy can be performed safely if particular steps, such as avoidance of a uterine manipulator, are followed. We await definitive results from prospective trials to determine this.

As mentioned earlier, the uterine manipulator is an important safety and feasibility tool for MIS hysterectomy. When not utilized, surgeons may need to add additional ports and instrumentation to maneuver the uterus and may have difficulty completing hysterectomy via a MIS approach for obese patients. There are additional urologic safety concerns when uterine elevation and cervicovaginal delineation is missing. Therefore, surgeons should consider use of the uterine manipulator on a case-by-case basis, potentially avoiding its use when it is not felt to be of benefit. While the wealth of prospective data suggests that manipulators are most likely safe in hysterectomy for endometrial cancer, they should be avoided if a minimally invasive approach to cervical cancer is employed.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to report. Email her at [email protected].

References

1. N Engl J Med. 2018 Nov 15. doi: 10.1056/NEJMoa1806395.

2. Fertil Steril. 2011 Oct. doi: 10.1016/j.fertnstert.2011.07.1146.

3. Am J Obstet Gynecol. 2017 Jun. doi: 10.1016/j.ajog.2017.01.027.

4. Am J Obstet Gynecol. 2020 Jul 18. doi: 10.1016/j.ajog.2020.07.025.

5. J Clin Oncol. 2009 Nov 10. doi: 10.1200/JCO.2009.22.3248.

6. JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.2068.

7. Int J Gynecol Cancer. 2020. doi: 10.1136/ijgc-2020-001506.

Over the past 4 decades there has been increasing use of minimally invasive surgery (MIS) for gynecologic cancer, particularly endometrial and cervical cancers. Uterine manipulators are a device inserted into the uterine cavity during MIS approaches to aid in directing the uterus within the pelvis, facilitating access to the uterine blood supply, defining the cardinal ligaments, lateralizing the ureters, and delineating the cervicovaginal junction. However, concerns have been raised regarding whether these devices are safe to use when the uterine corpus or cervix contains cancer.

In 2018, the LACC trial was published and demonstrated decreased survival for patients with cervical cancer who had undergone radical hysterectomy via a minimally invasive route.¹ Several hypotheses were proposed to explain this finding including possible tumor disruption from use of a uterine manipulator. Regrettably, this study did not document manipulator use, and therefore its influence on outcomes could not be measured. However, since that time there has been honed interest into the potential negative influence of uterine manipulators on endometrial and cervical cancer surgery.

Uterine manipulators typically are inserted through the uterine cervix and reside in the endometrial cavity. It is often an inflated balloon which stabilizes the device within the cavity. Hypotheses for how they may contribute to the spread of malignancy include the massage of endometrial tumor from the pressure of the inflated balloon, facilitation of tumor dissemination through cervical lymphatics or vasculature as the manipulator traverses or punctures a cervical cancer, and possibly perforation of the uterine cavity during placement of the manipulator, and in doing so, contaminating the peritoneal cavity with endometrial or cervical cancer cells that have been dragged through with the device.

Interestingly, uterine manipulator placement is not the only time during which endometrial or cervical cancers may be disturbed prior to resection. Many diagnostic procedures such as cervical excisional procedures (loop electrosurgical excision procedure and conizations) or hysteroscopic resections cause significant intentional disruption of tumor. In the case of hysteroscopy for endometrial cancer, endometrial cancer cells have been detected in the peritoneal washings of endometrial cancer patients who have undergone this procedure, however, no worse outcomes have been associated when hysteroscopy was included as part of the diagnostic work-up, suggesting that more than simply efflux into the peritoneal cavity is necessary for those tumor cells to have metastatic potential.²

Indeed the data is mixed regarding oncologic outcomes with uterine manipulator use, especially for endometrial cancer. In one recent study the outcomes of 951 patients with endometrial cancer from seven Italian centers were evaluated.³ There was no difference in recurrence rates or disease-specific survival between the 579 patients in whom manipulators were used and the 372 patients in which surgery was performed without manipulators. More recently a Spanish study reported retrospectively on 2,661 patients at 15 centers and determined that use of a uterine manipulator (two-thirds of the cohort) was associated with a hazard ratio of 1.74 (95% confidence interval, 1.07-2.83) for risk of death.⁴ Unfortunately, in this study there were substantial differences between sites that used manipulators and those that did not. Additionally, while one would expect different patterns of recurrence if the manipulator was introducing a unique mechanism for metastasis, this was not observed between the manipulator and nonmanipulator arms. Finally, the groups were intrinsically different with respect to important risk factors such as lymphovascular space invasion, which might have contributed to the observed outcomes. It is important to recognize that, in both the LAP-2 and LACE trials, minimally invasive hysterectomy for endometrial cancer had been shown to have noninferior survival outcomes, compared with open hysterectomy.^5,6 While these large randomized, controlled trials did not capture uterine manipulator usage, presumably it was utilized in at least some or most cases, and without apparent significant negative effect.

In cervical cancer, there is more competing data raising concern regarding manipulator use. The SUCCOR study was completed in 2020 and included a retrospective evaluation of 1,272 patients who had undergone open or MIS radical hysterectomy for early stage cervical cancer across 126 European centers during 2013-2014.⁷ They were able to evaluate for variables, such as uterine manipulator use. While they found that recurrence was higher for patients who had MIS hysterectomy, the HR (2.07) was similar to the HR for recurrence (2.76) among those who had uterine manipulator use. Conversely, the hazard ratio for recurrence following MIS radical hysterectomy without a manipulator was comparable with the superior rates seen with open surgery. This study was retrospective and therefore is largely hypothesis generating, however it does raise the question of whether the technique of MIS radical hysterectomy can be performed safely if particular steps, such as avoidance of a uterine manipulator, are followed. We await definitive results from prospective trials to determine this.

As mentioned earlier, the uterine manipulator is an important safety and feasibility tool for MIS hysterectomy. When not utilized, surgeons may need to add additional ports and instrumentation to maneuver the uterus and may have difficulty completing hysterectomy via a MIS approach for obese patients. There are additional urologic safety concerns when uterine elevation and cervicovaginal delineation is missing. Therefore, surgeons should consider use of the uterine manipulator on a case-by-case basis, potentially avoiding its use when it is not felt to be of benefit. While the wealth of prospective data suggests that manipulators are most likely safe in hysterectomy for endometrial cancer, they should be avoided if a minimally invasive approach to cervical cancer is employed.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to report. Email her at [email protected].

References

1. N Engl J Med. 2018 Nov 15. doi: 10.1056/NEJMoa1806395.

2. Fertil Steril. 2011 Oct. doi: 10.1016/j.fertnstert.2011.07.1146.

3. Am J Obstet Gynecol. 2017 Jun. doi: 10.1016/j.ajog.2017.01.027.

4. Am J Obstet Gynecol. 2020 Jul 18. doi: 10.1016/j.ajog.2020.07.025.

5. J Clin Oncol. 2009 Nov 10. doi: 10.1200/JCO.2009.22.3248.

6. JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.2068.

7. Int J Gynecol Cancer. 2020. doi: 10.1136/ijgc-2020-001506.

Over the past 4 decades there has been increasing use of minimally invasive surgery (MIS) for gynecologic cancer, particularly endometrial and cervical cancers. Uterine manipulators are a device inserted into the uterine cavity during MIS approaches to aid in directing the uterus within the pelvis, facilitating access to the uterine blood supply, defining the cardinal ligaments, lateralizing the ureters, and delineating the cervicovaginal junction. However, concerns have been raised regarding whether these devices are safe to use when the uterine corpus or cervix contains cancer.

In 2018, the LACC trial was published and demonstrated decreased survival for patients with cervical cancer who had undergone radical hysterectomy via a minimally invasive route.¹ Several hypotheses were proposed to explain this finding including possible tumor disruption from use of a uterine manipulator. Regrettably, this study did not document manipulator use, and therefore its influence on outcomes could not be measured. However, since that time there has been honed interest into the potential negative influence of uterine manipulators on endometrial and cervical cancer surgery.

Uterine manipulators typically are inserted through the uterine cervix and reside in the endometrial cavity. It is often an inflated balloon which stabilizes the device within the cavity. Hypotheses for how they may contribute to the spread of malignancy include the massage of endometrial tumor from the pressure of the inflated balloon, facilitation of tumor dissemination through cervical lymphatics or vasculature as the manipulator traverses or punctures a cervical cancer, and possibly perforation of the uterine cavity during placement of the manipulator, and in doing so, contaminating the peritoneal cavity with endometrial or cervical cancer cells that have been dragged through with the device.

Interestingly, uterine manipulator placement is not the only time during which endometrial or cervical cancers may be disturbed prior to resection. Many diagnostic procedures such as cervical excisional procedures (loop electrosurgical excision procedure and conizations) or hysteroscopic resections cause significant intentional disruption of tumor. In the case of hysteroscopy for endometrial cancer, endometrial cancer cells have been detected in the peritoneal washings of endometrial cancer patients who have undergone this procedure, however, no worse outcomes have been associated when hysteroscopy was included as part of the diagnostic work-up, suggesting that more than simply efflux into the peritoneal cavity is necessary for those tumor cells to have metastatic potential.²

Indeed the data is mixed regarding oncologic outcomes with uterine manipulator use, especially for endometrial cancer. In one recent study the outcomes of 951 patients with endometrial cancer from seven Italian centers were evaluated.³ There was no difference in recurrence rates or disease-specific survival between the 579 patients in whom manipulators were used and the 372 patients in which surgery was performed without manipulators. More recently a Spanish study reported retrospectively on 2,661 patients at 15 centers and determined that use of a uterine manipulator (two-thirds of the cohort) was associated with a hazard ratio of 1.74 (95% confidence interval, 1.07-2.83) for risk of death.⁴ Unfortunately, in this study there were substantial differences between sites that used manipulators and those that did not. Additionally, while one would expect different patterns of recurrence if the manipulator was introducing a unique mechanism for metastasis, this was not observed between the manipulator and nonmanipulator arms. Finally, the groups were intrinsically different with respect to important risk factors such as lymphovascular space invasion, which might have contributed to the observed outcomes. It is important to recognize that, in both the LAP-2 and LACE trials, minimally invasive hysterectomy for endometrial cancer had been shown to have noninferior survival outcomes, compared with open hysterectomy.^5,6 While these large randomized, controlled trials did not capture uterine manipulator usage, presumably it was utilized in at least some or most cases, and without apparent significant negative effect.

In cervical cancer, there is more competing data raising concern regarding manipulator use. The SUCCOR study was completed in 2020 and included a retrospective evaluation of 1,272 patients who had undergone open or MIS radical hysterectomy for early stage cervical cancer across 126 European centers during 2013-2014.⁷ They were able to evaluate for variables, such as uterine manipulator use. While they found that recurrence was higher for patients who had MIS hysterectomy, the HR (2.07) was similar to the HR for recurrence (2.76) among those who had uterine manipulator use. Conversely, the hazard ratio for recurrence following MIS radical hysterectomy without a manipulator was comparable with the superior rates seen with open surgery. This study was retrospective and therefore is largely hypothesis generating, however it does raise the question of whether the technique of MIS radical hysterectomy can be performed safely if particular steps, such as avoidance of a uterine manipulator, are followed. We await definitive results from prospective trials to determine this.

As mentioned earlier, the uterine manipulator is an important safety and feasibility tool for MIS hysterectomy. When not utilized, surgeons may need to add additional ports and instrumentation to maneuver the uterus and may have difficulty completing hysterectomy via a MIS approach for obese patients. There are additional urologic safety concerns when uterine elevation and cervicovaginal delineation is missing. Therefore, surgeons should consider use of the uterine manipulator on a case-by-case basis, potentially avoiding its use when it is not felt to be of benefit. While the wealth of prospective data suggests that manipulators are most likely safe in hysterectomy for endometrial cancer, they should be avoided if a minimally invasive approach to cervical cancer is employed.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to report. Email her at [email protected].

References

1. N Engl J Med. 2018 Nov 15. doi: 10.1056/NEJMoa1806395.

2. Fertil Steril. 2011 Oct. doi: 10.1016/j.fertnstert.2011.07.1146.

3. Am J Obstet Gynecol. 2017 Jun. doi: 10.1016/j.ajog.2017.01.027.

4. Am J Obstet Gynecol. 2020 Jul 18. doi: 10.1016/j.ajog.2020.07.025.

5. J Clin Oncol. 2009 Nov 10. doi: 10.1200/JCO.2009.22.3248.

6. JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.2068.

7. Int J Gynecol Cancer. 2020. doi: 10.1136/ijgc-2020-001506.

Sleep specialists might want to take a closer look at the connections between obstructive sleep apnea, chronic pain, and reported pain intensity in younger patients. Young adults with a diagnosis of obstructive sleep apnea (OSA) are more likely to report moderate to severe pain intensity, compared with their peers who do not have the diagnosis, results from a large cross-sectional analysis of veterans showed.

“Because of the high burden of chronic pain conditions in younger adults, this study highlights the need to understand the impact of OSA diagnosis and treatment on pain intensity,” researchers led by Wardah Athar, a graduate student at Yale University, New Haven, Conn., and Lori A. Bastian, MD, MPH, a professor of internal medicine at Yale, wrote in an article published in the Annals of the American Thoracic Society. “This understanding would then help inform the development of interventions to promote screening for OSA among young adults with chronic pain and pain management among those with diagnosed OSA.”

In an effort to assess whether young adults with diagnosed OSA are more likely to report higher pain intensity, compared with those without OSA, the researchers drew from a sample of 858,226 veterans from Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn who had at least one visit to a VA clinic between 2001 and 2014. They used ICD-9 codes to identify OSA and assessed self-reported responses to pain measures on a 0-10 numeric scale which were recorded in each veteran’s EMR. Next, they averaged pain intensity responses over a 12-month period and categorized them as none (0), mild (1-3), and moderate/severe (4–10). Covariates included age, sex, education, race, mental health diagnoses, headache diagnoses, pain diagnoses, hypertension, diabetes, body mass index, and smoking status. The researchers used multivariate logistic regression models and multiple imputation to generate values for missing variables.

The mean age of the patients was 30 years, 64% were White, 17% were Black, 12% were Hispanic, and remainder were other/unknown race/ethnicity. Ninety percent were male, and 20% had greater than a high school education. Of the 858,226 patients, 91,244 (11%) had a diagnosis of OSA. Compared with patients who had no diagnosis of OSA, the unadjusted odds of reporting moderate/severe pain was 48% higher among those with OSA (odds ratio 1.48; P < .0001). After the researchers adjusted for all covariates in the model, the association between OSA and moderate/severe pain remained significant though attenuated, with an adjusted odds ratio of 1.09 (P < .0001).

Several characteristics were different between those who had a diagnosis of OSA and those who did not, including age (a mean of 36 vs. 26 years, respectively) and having the following diagnoses: pain (36% vs. 16%), headache (28% vs. 14%), diabetes (12% vs. 2%), hypertension (40% vs. 12%), and a body mass index of 30 kg/m² or greater (69% vs. 35%). Certain psychiatric disorders were also common among patients with OSA, including major depressive disorder (20% vs. 10%), posttraumatic stress disorder (50% vs. 30%), and substance use disorder (26% vs. 17%). Patients with OSA were also more likely to have been prescribed benzodiazepines or opioids within 90 days of their OSA diagnosis. Although men were more likely to have a diagnosis of OSA, no differences related to sex in the association of OSA and pain were observed in sex-based stratified analyses.

“Based on these results, we suggest more thorough and more frequent pain intensity screening in patients with OSA, particularly in those patients who are younger than 60 years old without significant comorbid illness,” the researchers concluded. “Furthermore, we also recommend increased OSA screening for patients with moderate/severe pain intensity and pain diagnoses.” One tool they recommend is the STOP-Bang (Snoring, Tiredness, Observed Apnea, Blood Pressure, Body Mass Index, Age, Neck Circumference, and Gender) questionnaire, which has been validated in multiple settings.

Commenting on the findings of this study, Krishna M. Sundar, MD, FCCP, medical director of the Sleep-Wake Center at the University of Utah, Salt Lake City, commended the study design. “One of the problems with sleep apnea studies is that there are always confounding effects, especially from BMI. This is a population that has a significant medical burden of disease, but I think this is a well-done study to look at the relationship between pain and OSA in a younger population. The authors tried to adjust for all these confounders and they still found a significant association. This indicates that sleep affects one’s pain threshold. And sleep apnea, by mechanisms still yet to be defined, also alters that pain threshold. It may also affect the expression of pain or management of pain, making treatment more problematic in this population,” he said in an interview.

A key limitation of the study, he continued, was the fact it evaluated only one aspect of sleep: OSA. “They didn’t look at duration of sleep, comorbid insomnia, or fragmentation of sleep from apnea or from other causes,” Dr. Sundar said. “We have multiple ways of treating sleep apnea. Clearly, we need studies of treating sleep apnea with [continuous positive airway pressure] and how that affects the occurrence of pain. The relevant practical aspect of this is that there are pain clinics all over the country that should screen for sleep apnea. Along the same lines, sleep practitioners should be aware that pain has an important association with sleep apnea.”

The study was supported by the Health Services Research & Development in the Department of Veterans Affairs of the Veterans Health Administration, the Yale School of Medicine Medical Student Fellowship, and the U.S. National Institutes of Health.

[email protected]

SOURCE: Athar W et al. Ann Am Thorac Soc. 2020;17(10):1273-48.

Correction, 10/28/20: An earlier version of this article misstated Wardah Athar's name in the photo caption.

Sleep specialists might want to take a closer look at the connections between obstructive sleep apnea, chronic pain, and reported pain intensity in younger patients. Young adults with a diagnosis of obstructive sleep apnea (OSA) are more likely to report moderate to severe pain intensity, compared with their peers who do not have the diagnosis, results from a large cross-sectional analysis of veterans showed.

“Because of the high burden of chronic pain conditions in younger adults, this study highlights the need to understand the impact of OSA diagnosis and treatment on pain intensity,” researchers led by Wardah Athar, a graduate student at Yale University, New Haven, Conn., and Lori A. Bastian, MD, MPH, a professor of internal medicine at Yale, wrote in an article published in the Annals of the American Thoracic Society. “This understanding would then help inform the development of interventions to promote screening for OSA among young adults with chronic pain and pain management among those with diagnosed OSA.”

In an effort to assess whether young adults with diagnosed OSA are more likely to report higher pain intensity, compared with those without OSA, the researchers drew from a sample of 858,226 veterans from Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn who had at least one visit to a VA clinic between 2001 and 2014. They used ICD-9 codes to identify OSA and assessed self-reported responses to pain measures on a 0-10 numeric scale which were recorded in each veteran’s EMR. Next, they averaged pain intensity responses over a 12-month period and categorized them as none (0), mild (1-3), and moderate/severe (4–10). Covariates included age, sex, education, race, mental health diagnoses, headache diagnoses, pain diagnoses, hypertension, diabetes, body mass index, and smoking status. The researchers used multivariate logistic regression models and multiple imputation to generate values for missing variables.

The mean age of the patients was 30 years, 64% were White, 17% were Black, 12% were Hispanic, and remainder were other/unknown race/ethnicity. Ninety percent were male, and 20% had greater than a high school education. Of the 858,226 patients, 91,244 (11%) had a diagnosis of OSA. Compared with patients who had no diagnosis of OSA, the unadjusted odds of reporting moderate/severe pain was 48% higher among those with OSA (odds ratio 1.48; P < .0001). After the researchers adjusted for all covariates in the model, the association between OSA and moderate/severe pain remained significant though attenuated, with an adjusted odds ratio of 1.09 (P < .0001).

Several characteristics were different between those who had a diagnosis of OSA and those who did not, including age (a mean of 36 vs. 26 years, respectively) and having the following diagnoses: pain (36% vs. 16%), headache (28% vs. 14%), diabetes (12% vs. 2%), hypertension (40% vs. 12%), and a body mass index of 30 kg/m² or greater (69% vs. 35%). Certain psychiatric disorders were also common among patients with OSA, including major depressive disorder (20% vs. 10%), posttraumatic stress disorder (50% vs. 30%), and substance use disorder (26% vs. 17%). Patients with OSA were also more likely to have been prescribed benzodiazepines or opioids within 90 days of their OSA diagnosis. Although men were more likely to have a diagnosis of OSA, no differences related to sex in the association of OSA and pain were observed in sex-based stratified analyses.

“Based on these results, we suggest more thorough and more frequent pain intensity screening in patients with OSA, particularly in those patients who are younger than 60 years old without significant comorbid illness,” the researchers concluded. “Furthermore, we also recommend increased OSA screening for patients with moderate/severe pain intensity and pain diagnoses.” One tool they recommend is the STOP-Bang (Snoring, Tiredness, Observed Apnea, Blood Pressure, Body Mass Index, Age, Neck Circumference, and Gender) questionnaire, which has been validated in multiple settings.

Commenting on the findings of this study, Krishna M. Sundar, MD, FCCP, medical director of the Sleep-Wake Center at the University of Utah, Salt Lake City, commended the study design. “One of the problems with sleep apnea studies is that there are always confounding effects, especially from BMI. This is a population that has a significant medical burden of disease, but I think this is a well-done study to look at the relationship between pain and OSA in a younger population. The authors tried to adjust for all these confounders and they still found a significant association. This indicates that sleep affects one’s pain threshold. And sleep apnea, by mechanisms still yet to be defined, also alters that pain threshold. It may also affect the expression of pain or management of pain, making treatment more problematic in this population,” he said in an interview.

A key limitation of the study, he continued, was the fact it evaluated only one aspect of sleep: OSA. “They didn’t look at duration of sleep, comorbid insomnia, or fragmentation of sleep from apnea or from other causes,” Dr. Sundar said. “We have multiple ways of treating sleep apnea. Clearly, we need studies of treating sleep apnea with [continuous positive airway pressure] and how that affects the occurrence of pain. The relevant practical aspect of this is that there are pain clinics all over the country that should screen for sleep apnea. Along the same lines, sleep practitioners should be aware that pain has an important association with sleep apnea.”

The study was supported by the Health Services Research & Development in the Department of Veterans Affairs of the Veterans Health Administration, the Yale School of Medicine Medical Student Fellowship, and the U.S. National Institutes of Health.

[email protected]

SOURCE: Athar W et al. Ann Am Thorac Soc. 2020;17(10):1273-48.

Correction, 10/28/20: An earlier version of this article misstated Wardah Athar's name in the photo caption.

Sleep specialists might want to take a closer look at the connections between obstructive sleep apnea, chronic pain, and reported pain intensity in younger patients. Young adults with a diagnosis of obstructive sleep apnea (OSA) are more likely to report moderate to severe pain intensity, compared with their peers who do not have the diagnosis, results from a large cross-sectional analysis of veterans showed.

“Because of the high burden of chronic pain conditions in younger adults, this study highlights the need to understand the impact of OSA diagnosis and treatment on pain intensity,” researchers led by Wardah Athar, a graduate student at Yale University, New Haven, Conn., and Lori A. Bastian, MD, MPH, a professor of internal medicine at Yale, wrote in an article published in the Annals of the American Thoracic Society. “This understanding would then help inform the development of interventions to promote screening for OSA among young adults with chronic pain and pain management among those with diagnosed OSA.”

In an effort to assess whether young adults with diagnosed OSA are more likely to report higher pain intensity, compared with those without OSA, the researchers drew from a sample of 858,226 veterans from Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn who had at least one visit to a VA clinic between 2001 and 2014. They used ICD-9 codes to identify OSA and assessed self-reported responses to pain measures on a 0-10 numeric scale which were recorded in each veteran’s EMR. Next, they averaged pain intensity responses over a 12-month period and categorized them as none (0), mild (1-3), and moderate/severe (4–10). Covariates included age, sex, education, race, mental health diagnoses, headache diagnoses, pain diagnoses, hypertension, diabetes, body mass index, and smoking status. The researchers used multivariate logistic regression models and multiple imputation to generate values for missing variables.

The mean age of the patients was 30 years, 64% were White, 17% were Black, 12% were Hispanic, and remainder were other/unknown race/ethnicity. Ninety percent were male, and 20% had greater than a high school education. Of the 858,226 patients, 91,244 (11%) had a diagnosis of OSA. Compared with patients who had no diagnosis of OSA, the unadjusted odds of reporting moderate/severe pain was 48% higher among those with OSA (odds ratio 1.48; P < .0001). After the researchers adjusted for all covariates in the model, the association between OSA and moderate/severe pain remained significant though attenuated, with an adjusted odds ratio of 1.09 (P < .0001).

Several characteristics were different between those who had a diagnosis of OSA and those who did not, including age (a mean of 36 vs. 26 years, respectively) and having the following diagnoses: pain (36% vs. 16%), headache (28% vs. 14%), diabetes (12% vs. 2%), hypertension (40% vs. 12%), and a body mass index of 30 kg/m² or greater (69% vs. 35%). Certain psychiatric disorders were also common among patients with OSA, including major depressive disorder (20% vs. 10%), posttraumatic stress disorder (50% vs. 30%), and substance use disorder (26% vs. 17%). Patients with OSA were also more likely to have been prescribed benzodiazepines or opioids within 90 days of their OSA diagnosis. Although men were more likely to have a diagnosis of OSA, no differences related to sex in the association of OSA and pain were observed in sex-based stratified analyses.

“Based on these results, we suggest more thorough and more frequent pain intensity screening in patients with OSA, particularly in those patients who are younger than 60 years old without significant comorbid illness,” the researchers concluded. “Furthermore, we also recommend increased OSA screening for patients with moderate/severe pain intensity and pain diagnoses.” One tool they recommend is the STOP-Bang (Snoring, Tiredness, Observed Apnea, Blood Pressure, Body Mass Index, Age, Neck Circumference, and Gender) questionnaire, which has been validated in multiple settings.

Commenting on the findings of this study, Krishna M. Sundar, MD, FCCP, medical director of the Sleep-Wake Center at the University of Utah, Salt Lake City, commended the study design. “One of the problems with sleep apnea studies is that there are always confounding effects, especially from BMI. This is a population that has a significant medical burden of disease, but I think this is a well-done study to look at the relationship between pain and OSA in a younger population. The authors tried to adjust for all these confounders and they still found a significant association. This indicates that sleep affects one’s pain threshold. And sleep apnea, by mechanisms still yet to be defined, also alters that pain threshold. It may also affect the expression of pain or management of pain, making treatment more problematic in this population,” he said in an interview.

A key limitation of the study, he continued, was the fact it evaluated only one aspect of sleep: OSA. “They didn’t look at duration of sleep, comorbid insomnia, or fragmentation of sleep from apnea or from other causes,” Dr. Sundar said. “We have multiple ways of treating sleep apnea. Clearly, we need studies of treating sleep apnea with [continuous positive airway pressure] and how that affects the occurrence of pain. The relevant practical aspect of this is that there are pain clinics all over the country that should screen for sleep apnea. Along the same lines, sleep practitioners should be aware that pain has an important association with sleep apnea.”

The study was supported by the Health Services Research & Development in the Department of Veterans Affairs of the Veterans Health Administration, the Yale School of Medicine Medical Student Fellowship, and the U.S. National Institutes of Health.

[email protected]

SOURCE: Athar W et al. Ann Am Thorac Soc. 2020;17(10):1273-48.

Correction, 10/28/20: An earlier version of this article misstated Wardah Athar's name in the photo caption.

New guidelines recommend against retreatment with poly (ADP-ribose) polymerase (PARP) inhibitors in women with epithelial ovarian, tubal, or primary peritoneal cancer (EOC). However, trials investigating retreatment are underway, so this recommendation may change.

The guidelines, from the American Society of Clinical Oncology (ASCO), do not recommend PARP inhibitors for the initial treatment of stage I-II EOC.

However, PARP inhibitor maintenance should be offered to women with newly diagnosed stage III-IV EOC who achieved a complete or partial response with first-line platinum-based chemotherapy, according to the guidelines. Niraparib can be offered to all women meeting those criteria, while olaparib can be considered for patients with mutations in BRCA1/2.

The guidelines, published in the Journal of Clinical Oncology, are based on a systematic review of recent randomized PARP inhibitor trials, including PRIMA and SOLO1, among others.

What’s not available now is overall survival results from key clinical trials, the guideline authors noted. They added that further research is needed to address the issue of conserving platinum sensitivity in patients with disease progression on or after PARP inhibitor maintenance.

“Given the expectation that early treatment may confer the best outcome, maintenance therapy with PARP inhibitors should be offered, with these caveats,” the authors wrote.

Olaparib can also be added to bevacizumab maintenance therapy following response to first-line chemotherapy plus bevacizumab, according to the guidelines, which also address PARP inhibitor use for women with recurrent EOC, as well as management of adverse events.

The guidelines recommend against pairing PARP inhibitors with chemotherapy, targeted therapy, or immunotherapy outside a clinical trial.
 

Which drug, which setting, which dose?

This new ASCO guidelines may help cut through the complexity of treatment decision-making for women with EOC, according to Roisin E. O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York.

“Today as clinicians, we have a whole range of opportunities to give our patients PARP inhibitors in the upfront and recurrent setting,” Dr. O’Cearbhaill said in an interview. “It is quite complicated to know which PARP inhibitor should be used in which setting and which patients.”

“We want to make sure that patients who would derive the most benefit from PARP inhibitors are offered these agents but also that we’re careful not to use PARP inhibitors in settings where there is little or no data,” added Dr. O’Cearbhaill, who was not involved in the drafting of the guidelines.

The ASCO guidelines provide a detailed review of 17 clinical trials to address key issues, including the histologic types of EOC and biomarker subsets for which PARP inhibitors are recommended in the newly diagnosed setting, as well as the settings, dose, and duration of treatment that are recommended for patients with recurrent EOC who have not yet received a PARP inhibitor.

While PARP inhibitors are generally well tolerated, some characteristic toxicities – such as anemia, neutropenia, thrombocytopenia, persistent cytopenias, and nausea – may warrant dose reductions, the guidelines state.

Special attention must be paid to low-grade adverse events since PARP inhibitors are administered continuously on a daily basis, according to the guidelines. If a dose is held because of a grade 2 adverse event, the subsequent dose should be reduced to avoid a second dose hold.

“Reescalation or resumption of the initial dose is never recommended,” the guidelines state.
 

Retreatment

Dr. O’Cearbhaill said she is eager to see future guidelines addressing PARP inhibitor retreatment following disease progression, especially since more and more patients will receive these agents in the upfront setting.

Right now, there is little data available to address PARP inhibitor retreatment. However, the ASCO guidelines do mention the ongoing OReO/ENGOT OV-38 phase 3 trial of maintenance retreatment with olaparib in women with EOC.

This study, which includes patients who previously received a PARP inhibitor and who are responding to additional platinum-based chemotherapy, has an estimated completion date in May 2021, according to details on ClinicalTrials.gov.

That’s one of several trials designed to determine how best to incorporate PARP inhibitor retreatment into the treatment paradigm, according to Dr. O’Cearbhaill.

“Even if a high proportion of patients aren’t ultimately cured by this approach, if we can delay progression of disease by the order of months or even years, whilst proactively managing side effects, it would make such a big difference for patients,” she said. “It allows them to have a better quality of life and go about their daily activities without symptomatic ovarian cancer.”

Cochairs of the ASCO expert panel for the guidelines were William P. Tew, MD, of Memorial Sloan Kettering Cancer Center in New York, and Elise C. Kohn, MD, of the National Cancer Institute in Bethesda, Md. Dr. Tew and Dr. Kohn provided no disclosures, while their coauthors reported disclosures related to Roche, AstraZeneca, Tesaro, Clovis Oncology, Merck, Seattle Genetics, and other companies. Dr. O’Cearbhaill disclosed that she is a coauthor on the PRIMA/ENGOT-OV26/GOG-3012 phase 3 clinical trial (NCT02655016) and serves on the steering committee for DUO-O (NCT0373643). She reported personal fees from Clovis, Tesaro, Regeneron, and GlaxoSmithKline.

SOURCE: Tew WP et al. J Clin Oncol. 2020 Aug 13. doi: 10.1200/JCO.20.01924.

New guidelines recommend against retreatment with poly (ADP-ribose) polymerase (PARP) inhibitors in women with epithelial ovarian, tubal, or primary peritoneal cancer (EOC). However, trials investigating retreatment are underway, so this recommendation may change.

The guidelines, from the American Society of Clinical Oncology (ASCO), do not recommend PARP inhibitors for the initial treatment of stage I-II EOC.

However, PARP inhibitor maintenance should be offered to women with newly diagnosed stage III-IV EOC who achieved a complete or partial response with first-line platinum-based chemotherapy, according to the guidelines. Niraparib can be offered to all women meeting those criteria, while olaparib can be considered for patients with mutations in BRCA1/2.

The guidelines, published in the Journal of Clinical Oncology, are based on a systematic review of recent randomized PARP inhibitor trials, including PRIMA and SOLO1, among others.

What’s not available now is overall survival results from key clinical trials, the guideline authors noted. They added that further research is needed to address the issue of conserving platinum sensitivity in patients with disease progression on or after PARP inhibitor maintenance.

“Given the expectation that early treatment may confer the best outcome, maintenance therapy with PARP inhibitors should be offered, with these caveats,” the authors wrote.

Olaparib can also be added to bevacizumab maintenance therapy following response to first-line chemotherapy plus bevacizumab, according to the guidelines, which also address PARP inhibitor use for women with recurrent EOC, as well as management of adverse events.

The guidelines recommend against pairing PARP inhibitors with chemotherapy, targeted therapy, or immunotherapy outside a clinical trial.
 

Which drug, which setting, which dose?

This new ASCO guidelines may help cut through the complexity of treatment decision-making for women with EOC, according to Roisin E. O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York.

“Today as clinicians, we have a whole range of opportunities to give our patients PARP inhibitors in the upfront and recurrent setting,” Dr. O’Cearbhaill said in an interview. “It is quite complicated to know which PARP inhibitor should be used in which setting and which patients.”

“We want to make sure that patients who would derive the most benefit from PARP inhibitors are offered these agents but also that we’re careful not to use PARP inhibitors in settings where there is little or no data,” added Dr. O’Cearbhaill, who was not involved in the drafting of the guidelines.

The ASCO guidelines provide a detailed review of 17 clinical trials to address key issues, including the histologic types of EOC and biomarker subsets for which PARP inhibitors are recommended in the newly diagnosed setting, as well as the settings, dose, and duration of treatment that are recommended for patients with recurrent EOC who have not yet received a PARP inhibitor.

While PARP inhibitors are generally well tolerated, some characteristic toxicities – such as anemia, neutropenia, thrombocytopenia, persistent cytopenias, and nausea – may warrant dose reductions, the guidelines state.

Special attention must be paid to low-grade adverse events since PARP inhibitors are administered continuously on a daily basis, according to the guidelines. If a dose is held because of a grade 2 adverse event, the subsequent dose should be reduced to avoid a second dose hold.

“Reescalation or resumption of the initial dose is never recommended,” the guidelines state.
 

Retreatment

Dr. O’Cearbhaill said she is eager to see future guidelines addressing PARP inhibitor retreatment following disease progression, especially since more and more patients will receive these agents in the upfront setting.

Right now, there is little data available to address PARP inhibitor retreatment. However, the ASCO guidelines do mention the ongoing OReO/ENGOT OV-38 phase 3 trial of maintenance retreatment with olaparib in women with EOC.

This study, which includes patients who previously received a PARP inhibitor and who are responding to additional platinum-based chemotherapy, has an estimated completion date in May 2021, according to details on ClinicalTrials.gov.

That’s one of several trials designed to determine how best to incorporate PARP inhibitor retreatment into the treatment paradigm, according to Dr. O’Cearbhaill.

“Even if a high proportion of patients aren’t ultimately cured by this approach, if we can delay progression of disease by the order of months or even years, whilst proactively managing side effects, it would make such a big difference for patients,” she said. “It allows them to have a better quality of life and go about their daily activities without symptomatic ovarian cancer.”

Cochairs of the ASCO expert panel for the guidelines were William P. Tew, MD, of Memorial Sloan Kettering Cancer Center in New York, and Elise C. Kohn, MD, of the National Cancer Institute in Bethesda, Md. Dr. Tew and Dr. Kohn provided no disclosures, while their coauthors reported disclosures related to Roche, AstraZeneca, Tesaro, Clovis Oncology, Merck, Seattle Genetics, and other companies. Dr. O’Cearbhaill disclosed that she is a coauthor on the PRIMA/ENGOT-OV26/GOG-3012 phase 3 clinical trial (NCT02655016) and serves on the steering committee for DUO-O (NCT0373643). She reported personal fees from Clovis, Tesaro, Regeneron, and GlaxoSmithKline.

SOURCE: Tew WP et al. J Clin Oncol. 2020 Aug 13. doi: 10.1200/JCO.20.01924.

New guidelines recommend against retreatment with poly (ADP-ribose) polymerase (PARP) inhibitors in women with epithelial ovarian, tubal, or primary peritoneal cancer (EOC). However, trials investigating retreatment are underway, so this recommendation may change.

The guidelines, from the American Society of Clinical Oncology (ASCO), do not recommend PARP inhibitors for the initial treatment of stage I-II EOC.

However, PARP inhibitor maintenance should be offered to women with newly diagnosed stage III-IV EOC who achieved a complete or partial response with first-line platinum-based chemotherapy, according to the guidelines. Niraparib can be offered to all women meeting those criteria, while olaparib can be considered for patients with mutations in BRCA1/2.

The guidelines, published in the Journal of Clinical Oncology, are based on a systematic review of recent randomized PARP inhibitor trials, including PRIMA and SOLO1, among others.

What’s not available now is overall survival results from key clinical trials, the guideline authors noted. They added that further research is needed to address the issue of conserving platinum sensitivity in patients with disease progression on or after PARP inhibitor maintenance.

“Given the expectation that early treatment may confer the best outcome, maintenance therapy with PARP inhibitors should be offered, with these caveats,” the authors wrote.

Olaparib can also be added to bevacizumab maintenance therapy following response to first-line chemotherapy plus bevacizumab, according to the guidelines, which also address PARP inhibitor use for women with recurrent EOC, as well as management of adverse events.

The guidelines recommend against pairing PARP inhibitors with chemotherapy, targeted therapy, or immunotherapy outside a clinical trial.
 

Which drug, which setting, which dose?

This new ASCO guidelines may help cut through the complexity of treatment decision-making for women with EOC, according to Roisin E. O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York.

“Today as clinicians, we have a whole range of opportunities to give our patients PARP inhibitors in the upfront and recurrent setting,” Dr. O’Cearbhaill said in an interview. “It is quite complicated to know which PARP inhibitor should be used in which setting and which patients.”

“We want to make sure that patients who would derive the most benefit from PARP inhibitors are offered these agents but also that we’re careful not to use PARP inhibitors in settings where there is little or no data,” added Dr. O’Cearbhaill, who was not involved in the drafting of the guidelines.

The ASCO guidelines provide a detailed review of 17 clinical trials to address key issues, including the histologic types of EOC and biomarker subsets for which PARP inhibitors are recommended in the newly diagnosed setting, as well as the settings, dose, and duration of treatment that are recommended for patients with recurrent EOC who have not yet received a PARP inhibitor.

While PARP inhibitors are generally well tolerated, some characteristic toxicities – such as anemia, neutropenia, thrombocytopenia, persistent cytopenias, and nausea – may warrant dose reductions, the guidelines state.

Special attention must be paid to low-grade adverse events since PARP inhibitors are administered continuously on a daily basis, according to the guidelines. If a dose is held because of a grade 2 adverse event, the subsequent dose should be reduced to avoid a second dose hold.

“Reescalation or resumption of the initial dose is never recommended,” the guidelines state.
 

Retreatment

Dr. O’Cearbhaill said she is eager to see future guidelines addressing PARP inhibitor retreatment following disease progression, especially since more and more patients will receive these agents in the upfront setting.

Right now, there is little data available to address PARP inhibitor retreatment. However, the ASCO guidelines do mention the ongoing OReO/ENGOT OV-38 phase 3 trial of maintenance retreatment with olaparib in women with EOC.

This study, which includes patients who previously received a PARP inhibitor and who are responding to additional platinum-based chemotherapy, has an estimated completion date in May 2021, according to details on ClinicalTrials.gov.

That’s one of several trials designed to determine how best to incorporate PARP inhibitor retreatment into the treatment paradigm, according to Dr. O’Cearbhaill.

“Even if a high proportion of patients aren’t ultimately cured by this approach, if we can delay progression of disease by the order of months or even years, whilst proactively managing side effects, it would make such a big difference for patients,” she said. “It allows them to have a better quality of life and go about their daily activities without symptomatic ovarian cancer.”

Cochairs of the ASCO expert panel for the guidelines were William P. Tew, MD, of Memorial Sloan Kettering Cancer Center in New York, and Elise C. Kohn, MD, of the National Cancer Institute in Bethesda, Md. Dr. Tew and Dr. Kohn provided no disclosures, while their coauthors reported disclosures related to Roche, AstraZeneca, Tesaro, Clovis Oncology, Merck, Seattle Genetics, and other companies. Dr. O’Cearbhaill disclosed that she is a coauthor on the PRIMA/ENGOT-OV26/GOG-3012 phase 3 clinical trial (NCT02655016) and serves on the steering committee for DUO-O (NCT0373643). She reported personal fees from Clovis, Tesaro, Regeneron, and GlaxoSmithKline.

SOURCE: Tew WP et al. J Clin Oncol. 2020 Aug 13. doi: 10.1200/JCO.20.01924.

Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.

But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”

Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”

Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”

Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”

Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”

As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”

Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”

This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.

Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.

But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”

Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”

Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”

Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”

Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”

As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”

Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”

This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.

Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.

But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”

Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”

Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”

Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”

Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”

As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”

Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”

This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Updated assessment and treatment options provide more tools to help clinicians manage osteoporosis and reduce fracture risk, according to Rick Pope, MPAS, PA-C.

iStock/Thinkstock

Criteria from the National Osteoporosis Foundation for the diagnosis of osteoporosis expanded in 2020 to include a T score measure of –2.5 or less at the wrist in postmenopausal women or in men aged 50 years and older (in addition to existing criteria of –2.5 or lower T scores at the lumbar spine, femoral neck, or total hip), he said in a presentation at the virtual annual Metabolic and Endocrine Disease Summit by Global Academy for Medical Education.

Other updated diagnostic criteria for osteoporosis include a low-trauma hip fracture regardless of bone mineral density, and a history of fracture of the pelvis or wrist in the context of osteopenia (in addition to the existing criteria of fracture of the vertebrae or proximal humerus).

When a diagnosis of osteoporosis is established, the Fracture Risk Assessment Tool calculator continues to serve as useful tool that allows clinicians to easily input patient data and obtain a projection of fracture risk, Mr. Pope said.

During a clinical visit, be sure to measure patients’ height, and look for kyphosis to help evaluate fall risk. Progressive kyphosis is important because the head weight can increase to 40 pounds if the kyphosis progresses to 30 degrees, and puts further stress on the vertebrae, he emphasized. In addition, looking at gait is important, especially for older patients, said Mr. Pope. “I want to get an assessment of how steady they are on their feet.”

Vertebral fracture assessment (VFA) is a useful strategy to evaluate the spine for silent compression fractures, especially in someone who has lost 1.5 inches in height or is on chronic steroids, Mr. Pope said. VFA has several advantages, including lower cost and lower radiation exposure than plain radiographs of the spine.

In addition, trabecular bone score (TBS) allows clinicians to evaluate bone microarchitecture, and this score can serve as an important indicator of fracture risk, Mr. Pope said.

As for treatment options, managing skeletal health in osteoporosis patients includes advising patients on healthy lifestyle practices that include not only adequate calcium and vitamin D, but also smoking cessation and a combination of weight-bearing, dynamic balance, and resistive exercises, he noted.

When considering medications, patient factors determine the most appropriate drug to use, Mr. Pope emphasized.

Bisphosphonates remain an option for treatment and have shown effectiveness at reducing fracture risk in postmenopausal women with osteoporosis, but concerns persist about side effects such as osteonecrosis of the jaw and atypical femoral fractures (AFF), he noted.

Reassure patients that AFF is more of an issue with long-term bisphosphonate use, Mr. Pope said, citing a 2012 study in which the risk of atypical femoral fracture was 1.78 per 100,000 person-years among individuals with 0.1-1.9 years of bisphosphonate exposure, but this jumped to 113 per 100,000 person-years among those with 8-9.9 years of bisphosphonate exposure.

“Eight years seems to be the sweet spot,” before a significant increase, he said. In his clinic, clinicians stop patients at about 8 years of bisphosphonate treatment, and then consider restarting.

However, nonbisphosphonate treatments are also available, including the monoclonal antibody denosumab. “It is different than bisphosphonates, and the effect wears off rapidly,” said Mr. Pope. Also, creatinine clearance is not an issue with denosumab. However, when patients have gone past the 10-year mark, should be switched to an alternative treatment because of an increased fracture risk at that point.

One relatively new treatment, abaloparatide, is currently indicated only for postmenopausal women with osteoporosis. Data have shown an 86% reduction in vertebral fracture risk, but the drug carries a black-box warning for osteosarcoma, said Mr. Pope.

Romosozumab, another newcomer drug, is indicated only for postmenopausal osteoporotic women at high risk for fracture with multiple risk factors who have failed other therapies. Romosozumab carries a black-box warning for cardiovascular risk for those with a history of MI or stroke. “This is a completely different mechanism of action” from other drugs, Mr. Pope said. The drug is given twice a month for a total of 12 months, and must be administered by a health professional in an office setting.

Mr. Pope had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.

Updated assessment and treatment options provide more tools to help clinicians manage osteoporosis and reduce fracture risk, according to Rick Pope, MPAS, PA-C.

iStock/Thinkstock

Criteria from the National Osteoporosis Foundation for the diagnosis of osteoporosis expanded in 2020 to include a T score measure of –2.5 or less at the wrist in postmenopausal women or in men aged 50 years and older (in addition to existing criteria of –2.5 or lower T scores at the lumbar spine, femoral neck, or total hip), he said in a presentation at the virtual annual Metabolic and Endocrine Disease Summit by Global Academy for Medical Education.

Other updated diagnostic criteria for osteoporosis include a low-trauma hip fracture regardless of bone mineral density, and a history of fracture of the pelvis or wrist in the context of osteopenia (in addition to the existing criteria of fracture of the vertebrae or proximal humerus).

When a diagnosis of osteoporosis is established, the Fracture Risk Assessment Tool calculator continues to serve as useful tool that allows clinicians to easily input patient data and obtain a projection of fracture risk, Mr. Pope said.

During a clinical visit, be sure to measure patients’ height, and look for kyphosis to help evaluate fall risk. Progressive kyphosis is important because the head weight can increase to 40 pounds if the kyphosis progresses to 30 degrees, and puts further stress on the vertebrae, he emphasized. In addition, looking at gait is important, especially for older patients, said Mr. Pope. “I want to get an assessment of how steady they are on their feet.”

Vertebral fracture assessment (VFA) is a useful strategy to evaluate the spine for silent compression fractures, especially in someone who has lost 1.5 inches in height or is on chronic steroids, Mr. Pope said. VFA has several advantages, including lower cost and lower radiation exposure than plain radiographs of the spine.

In addition, trabecular bone score (TBS) allows clinicians to evaluate bone microarchitecture, and this score can serve as an important indicator of fracture risk, Mr. Pope said.

As for treatment options, managing skeletal health in osteoporosis patients includes advising patients on healthy lifestyle practices that include not only adequate calcium and vitamin D, but also smoking cessation and a combination of weight-bearing, dynamic balance, and resistive exercises, he noted.

When considering medications, patient factors determine the most appropriate drug to use, Mr. Pope emphasized.

Bisphosphonates remain an option for treatment and have shown effectiveness at reducing fracture risk in postmenopausal women with osteoporosis, but concerns persist about side effects such as osteonecrosis of the jaw and atypical femoral fractures (AFF), he noted.

Reassure patients that AFF is more of an issue with long-term bisphosphonate use, Mr. Pope said, citing a 2012 study in which the risk of atypical femoral fracture was 1.78 per 100,000 person-years among individuals with 0.1-1.9 years of bisphosphonate exposure, but this jumped to 113 per 100,000 person-years among those with 8-9.9 years of bisphosphonate exposure.

“Eight years seems to be the sweet spot,” before a significant increase, he said. In his clinic, clinicians stop patients at about 8 years of bisphosphonate treatment, and then consider restarting.

However, nonbisphosphonate treatments are also available, including the monoclonal antibody denosumab. “It is different than bisphosphonates, and the effect wears off rapidly,” said Mr. Pope. Also, creatinine clearance is not an issue with denosumab. However, when patients have gone past the 10-year mark, should be switched to an alternative treatment because of an increased fracture risk at that point.

One relatively new treatment, abaloparatide, is currently indicated only for postmenopausal women with osteoporosis. Data have shown an 86% reduction in vertebral fracture risk, but the drug carries a black-box warning for osteosarcoma, said Mr. Pope.

Romosozumab, another newcomer drug, is indicated only for postmenopausal osteoporotic women at high risk for fracture with multiple risk factors who have failed other therapies. Romosozumab carries a black-box warning for cardiovascular risk for those with a history of MI or stroke. “This is a completely different mechanism of action” from other drugs, Mr. Pope said. The drug is given twice a month for a total of 12 months, and must be administered by a health professional in an office setting.

Mr. Pope had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.

Updated assessment and treatment options provide more tools to help clinicians manage osteoporosis and reduce fracture risk, according to Rick Pope, MPAS, PA-C.

iStock/Thinkstock

Criteria from the National Osteoporosis Foundation for the diagnosis of osteoporosis expanded in 2020 to include a T score measure of –2.5 or less at the wrist in postmenopausal women or in men aged 50 years and older (in addition to existing criteria of –2.5 or lower T scores at the lumbar spine, femoral neck, or total hip), he said in a presentation at the virtual annual Metabolic and Endocrine Disease Summit by Global Academy for Medical Education.

Other updated diagnostic criteria for osteoporosis include a low-trauma hip fracture regardless of bone mineral density, and a history of fracture of the pelvis or wrist in the context of osteopenia (in addition to the existing criteria of fracture of the vertebrae or proximal humerus).

When a diagnosis of osteoporosis is established, the Fracture Risk Assessment Tool calculator continues to serve as useful tool that allows clinicians to easily input patient data and obtain a projection of fracture risk, Mr. Pope said.

During a clinical visit, be sure to measure patients’ height, and look for kyphosis to help evaluate fall risk. Progressive kyphosis is important because the head weight can increase to 40 pounds if the kyphosis progresses to 30 degrees, and puts further stress on the vertebrae, he emphasized. In addition, looking at gait is important, especially for older patients, said Mr. Pope. “I want to get an assessment of how steady they are on their feet.”

Vertebral fracture assessment (VFA) is a useful strategy to evaluate the spine for silent compression fractures, especially in someone who has lost 1.5 inches in height or is on chronic steroids, Mr. Pope said. VFA has several advantages, including lower cost and lower radiation exposure than plain radiographs of the spine.

In addition, trabecular bone score (TBS) allows clinicians to evaluate bone microarchitecture, and this score can serve as an important indicator of fracture risk, Mr. Pope said.

As for treatment options, managing skeletal health in osteoporosis patients includes advising patients on healthy lifestyle practices that include not only adequate calcium and vitamin D, but also smoking cessation and a combination of weight-bearing, dynamic balance, and resistive exercises, he noted.

When considering medications, patient factors determine the most appropriate drug to use, Mr. Pope emphasized.

Bisphosphonates remain an option for treatment and have shown effectiveness at reducing fracture risk in postmenopausal women with osteoporosis, but concerns persist about side effects such as osteonecrosis of the jaw and atypical femoral fractures (AFF), he noted.

Reassure patients that AFF is more of an issue with long-term bisphosphonate use, Mr. Pope said, citing a 2012 study in which the risk of atypical femoral fracture was 1.78 per 100,000 person-years among individuals with 0.1-1.9 years of bisphosphonate exposure, but this jumped to 113 per 100,000 person-years among those with 8-9.9 years of bisphosphonate exposure.

“Eight years seems to be the sweet spot,” before a significant increase, he said. In his clinic, clinicians stop patients at about 8 years of bisphosphonate treatment, and then consider restarting.

However, nonbisphosphonate treatments are also available, including the monoclonal antibody denosumab. “It is different than bisphosphonates, and the effect wears off rapidly,” said Mr. Pope. Also, creatinine clearance is not an issue with denosumab. However, when patients have gone past the 10-year mark, should be switched to an alternative treatment because of an increased fracture risk at that point.

One relatively new treatment, abaloparatide, is currently indicated only for postmenopausal women with osteoporosis. Data have shown an 86% reduction in vertebral fracture risk, but the drug carries a black-box warning for osteosarcoma, said Mr. Pope.

Romosozumab, another newcomer drug, is indicated only for postmenopausal osteoporotic women at high risk for fracture with multiple risk factors who have failed other therapies. Romosozumab carries a black-box warning for cardiovascular risk for those with a history of MI or stroke. “This is a completely different mechanism of action” from other drugs, Mr. Pope said. The drug is given twice a month for a total of 12 months, and must be administered by a health professional in an office setting.

Mr. Pope had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.

Is it time to consider chimeric antigen receptor (CAR) T-cell therapy for all relapsed/refractory diffuse large B-cell lymphoma patients? Maybe not, according to Andrew Zelenetz, MD, PhD.

CAR T-cell therapy has demonstrated activity in relapsed/refractory non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), transformed indolent NHL, and mantle cell lymphoma, and can provide durable complete responses in a portion of patients with chemorefractory disease, Dr. Zelenetz, chair of the National Comprehensive Cancer Network Lymphoma Guidelines Panel and a specialist in lymphoma at Memorial Sloan Kettering Cancer Center in New York, said at the NCCN Hematologic Malignancies Annual Congress.

In chemosensitive patients, however, its role requires further examination, especially given findings from a recent analysis of patients from the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showing comparable outcomes with high-dose chemotherapy and autologous stem cell rescue for patients with a positron emission testing–positive partial response (PR) after second-line chemotherapy, he said.

Of 249 patients who underwent a first autologous transplant for DLBCL between 2003 and 2018, received front-line rituximab chemotherapy, and had PET– or computed tomography–positive disease prior to transplant, 182 had early chemotherapy failure (within 12 months) and 67 had late chemotherapy failure (at 12 months or later) after therapy, according to findings from the study as reported at ASCO 2020.

The adjusted nonrelapse mortality rates in the early- and late-failure patients, respectively, were not significantly different at 7% and 3% at 1 year, and at 10% and 8% at 5 years. The corresponding progression/relapse rates were 41% and 35% at 1 year and 48% and 57% at 5 years; these were also not significantly different.

The adjusted progression-free survival (PFS) and overall survival (OS) in the groups at 5 years also did not differ significantly (PFS of 41% in both the early- and late-failure groups, and OS of 51% and 63%, respectively).

These outcomes are comparable to those seen with CAR T-cell therapy in refractory DLBCL patients in trials of CAR T-cell products, including the ZUMA-1 study of axicabtagene cyloleucel (Yescarta), which, in a 2019 update, showed survival plateaus of about 40% vs. the 5%-10% expected rate based on pre-CAR-T outcomes data; the JULIET trial of tisagenlecleucel (Kymriah), which showed survival plateaus in the range of 30%-35%; and the recently published TRANSCEND study of the investigational modified CAR-T product, lisocabtagene maraleucel, which also showed survival plateaus “in the range of 40%.”

“So all three agents are showing that CAR T cells represent a new treatment for diffuse large B-cell lymphoma in the relapsed/refractory setting,” Dr. Zelenetz said. “And as a result, [CAR T-cell therapy has] been included in the NCCN guidelines for transformed follicular lymphoma, for transformed marginal zone lymphoma, and for diffuse large B-cell lymphoma, as well as for refractory large B-cell lymphoma.

“But are CAR T cells absolutely required? Generally what we consider these days is that if you’re not in a PET-negative CR prior to high-dose therapy stem cell rescue, you should go on to CAR T cells,” Dr. Zelenetz said.

The analysis based on the CIBMTR registry data, however, suggests there may be other alternatives.

“The bottom line is that nonrelapse mortality was very low. Progression occurred in about half of the patients, but if we look at the overall and progression-free survival curves, there’s a plateau at around 45%,” Dr. Zelenetz said, explaining that the results are “very similar to the results that we’re getting in third-line treatment with CAR T cells, and this is a very similar population [of] PET-positive patients after second-line chemotherapy.”

CAR T-cell therapy can provide a durable CR in a portion of chemorefractory patients, and although there is room for improvement, “this represents a major step forward for these patients,” he said.

However, it’s not clear that CAR T cells are clearly superior to high-dose therapy and stem cell rescue for chemosensitive patients, he added, noting that “additional randomized trials are needed to answer this question, and they are ongoing as we speak.”

Dr. Zelenetz reported clinical research support or data safety monitoring board activity for BeiGene, Genentech, Juno Therapeutics, and MEI Pharma, and scientific advisory board, consulting, or expert witness activity for Celgene Corporation, Curries, Genentech, Gilead Sciences, Janssen Pharmaceutical Products, and several other pharmaceutical and biotechnology companies.
 

[email protected]

Is it time to consider chimeric antigen receptor (CAR) T-cell therapy for all relapsed/refractory diffuse large B-cell lymphoma patients? Maybe not, according to Andrew Zelenetz, MD, PhD.

CAR T-cell therapy has demonstrated activity in relapsed/refractory non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), transformed indolent NHL, and mantle cell lymphoma, and can provide durable complete responses in a portion of patients with chemorefractory disease, Dr. Zelenetz, chair of the National Comprehensive Cancer Network Lymphoma Guidelines Panel and a specialist in lymphoma at Memorial Sloan Kettering Cancer Center in New York, said at the NCCN Hematologic Malignancies Annual Congress.

In chemosensitive patients, however, its role requires further examination, especially given findings from a recent analysis of patients from the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showing comparable outcomes with high-dose chemotherapy and autologous stem cell rescue for patients with a positron emission testing–positive partial response (PR) after second-line chemotherapy, he said.

Of 249 patients who underwent a first autologous transplant for DLBCL between 2003 and 2018, received front-line rituximab chemotherapy, and had PET– or computed tomography–positive disease prior to transplant, 182 had early chemotherapy failure (within 12 months) and 67 had late chemotherapy failure (at 12 months or later) after therapy, according to findings from the study as reported at ASCO 2020.

The adjusted nonrelapse mortality rates in the early- and late-failure patients, respectively, were not significantly different at 7% and 3% at 1 year, and at 10% and 8% at 5 years. The corresponding progression/relapse rates were 41% and 35% at 1 year and 48% and 57% at 5 years; these were also not significantly different.

The adjusted progression-free survival (PFS) and overall survival (OS) in the groups at 5 years also did not differ significantly (PFS of 41% in both the early- and late-failure groups, and OS of 51% and 63%, respectively).

These outcomes are comparable to those seen with CAR T-cell therapy in refractory DLBCL patients in trials of CAR T-cell products, including the ZUMA-1 study of axicabtagene cyloleucel (Yescarta), which, in a 2019 update, showed survival plateaus of about 40% vs. the 5%-10% expected rate based on pre-CAR-T outcomes data; the JULIET trial of tisagenlecleucel (Kymriah), which showed survival plateaus in the range of 30%-35%; and the recently published TRANSCEND study of the investigational modified CAR-T product, lisocabtagene maraleucel, which also showed survival plateaus “in the range of 40%.”

“So all three agents are showing that CAR T cells represent a new treatment for diffuse large B-cell lymphoma in the relapsed/refractory setting,” Dr. Zelenetz said. “And as a result, [CAR T-cell therapy has] been included in the NCCN guidelines for transformed follicular lymphoma, for transformed marginal zone lymphoma, and for diffuse large B-cell lymphoma, as well as for refractory large B-cell lymphoma.

“But are CAR T cells absolutely required? Generally what we consider these days is that if you’re not in a PET-negative CR prior to high-dose therapy stem cell rescue, you should go on to CAR T cells,” Dr. Zelenetz said.

The analysis based on the CIBMTR registry data, however, suggests there may be other alternatives.

“The bottom line is that nonrelapse mortality was very low. Progression occurred in about half of the patients, but if we look at the overall and progression-free survival curves, there’s a plateau at around 45%,” Dr. Zelenetz said, explaining that the results are “very similar to the results that we’re getting in third-line treatment with CAR T cells, and this is a very similar population [of] PET-positive patients after second-line chemotherapy.”

CAR T-cell therapy can provide a durable CR in a portion of chemorefractory patients, and although there is room for improvement, “this represents a major step forward for these patients,” he said.

However, it’s not clear that CAR T cells are clearly superior to high-dose therapy and stem cell rescue for chemosensitive patients, he added, noting that “additional randomized trials are needed to answer this question, and they are ongoing as we speak.”

Dr. Zelenetz reported clinical research support or data safety monitoring board activity for BeiGene, Genentech, Juno Therapeutics, and MEI Pharma, and scientific advisory board, consulting, or expert witness activity for Celgene Corporation, Curries, Genentech, Gilead Sciences, Janssen Pharmaceutical Products, and several other pharmaceutical and biotechnology companies.
 

[email protected]

Is it time to consider chimeric antigen receptor (CAR) T-cell therapy for all relapsed/refractory diffuse large B-cell lymphoma patients? Maybe not, according to Andrew Zelenetz, MD, PhD.

CAR T-cell therapy has demonstrated activity in relapsed/refractory non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), transformed indolent NHL, and mantle cell lymphoma, and can provide durable complete responses in a portion of patients with chemorefractory disease, Dr. Zelenetz, chair of the National Comprehensive Cancer Network Lymphoma Guidelines Panel and a specialist in lymphoma at Memorial Sloan Kettering Cancer Center in New York, said at the NCCN Hematologic Malignancies Annual Congress.

In chemosensitive patients, however, its role requires further examination, especially given findings from a recent analysis of patients from the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showing comparable outcomes with high-dose chemotherapy and autologous stem cell rescue for patients with a positron emission testing–positive partial response (PR) after second-line chemotherapy, he said.

Of 249 patients who underwent a first autologous transplant for DLBCL between 2003 and 2018, received front-line rituximab chemotherapy, and had PET– or computed tomography–positive disease prior to transplant, 182 had early chemotherapy failure (within 12 months) and 67 had late chemotherapy failure (at 12 months or later) after therapy, according to findings from the study as reported at ASCO 2020.

The adjusted nonrelapse mortality rates in the early- and late-failure patients, respectively, were not significantly different at 7% and 3% at 1 year, and at 10% and 8% at 5 years. The corresponding progression/relapse rates were 41% and 35% at 1 year and 48% and 57% at 5 years; these were also not significantly different.

The adjusted progression-free survival (PFS) and overall survival (OS) in the groups at 5 years also did not differ significantly (PFS of 41% in both the early- and late-failure groups, and OS of 51% and 63%, respectively).

These outcomes are comparable to those seen with CAR T-cell therapy in refractory DLBCL patients in trials of CAR T-cell products, including the ZUMA-1 study of axicabtagene cyloleucel (Yescarta), which, in a 2019 update, showed survival plateaus of about 40% vs. the 5%-10% expected rate based on pre-CAR-T outcomes data; the JULIET trial of tisagenlecleucel (Kymriah), which showed survival plateaus in the range of 30%-35%; and the recently published TRANSCEND study of the investigational modified CAR-T product, lisocabtagene maraleucel, which also showed survival plateaus “in the range of 40%.”

“So all three agents are showing that CAR T cells represent a new treatment for diffuse large B-cell lymphoma in the relapsed/refractory setting,” Dr. Zelenetz said. “And as a result, [CAR T-cell therapy has] been included in the NCCN guidelines for transformed follicular lymphoma, for transformed marginal zone lymphoma, and for diffuse large B-cell lymphoma, as well as for refractory large B-cell lymphoma.

“But are CAR T cells absolutely required? Generally what we consider these days is that if you’re not in a PET-negative CR prior to high-dose therapy stem cell rescue, you should go on to CAR T cells,” Dr. Zelenetz said.

The analysis based on the CIBMTR registry data, however, suggests there may be other alternatives.

“The bottom line is that nonrelapse mortality was very low. Progression occurred in about half of the patients, but if we look at the overall and progression-free survival curves, there’s a plateau at around 45%,” Dr. Zelenetz said, explaining that the results are “very similar to the results that we’re getting in third-line treatment with CAR T cells, and this is a very similar population [of] PET-positive patients after second-line chemotherapy.”

CAR T-cell therapy can provide a durable CR in a portion of chemorefractory patients, and although there is room for improvement, “this represents a major step forward for these patients,” he said.

However, it’s not clear that CAR T cells are clearly superior to high-dose therapy and stem cell rescue for chemosensitive patients, he added, noting that “additional randomized trials are needed to answer this question, and they are ongoing as we speak.”

Dr. Zelenetz reported clinical research support or data safety monitoring board activity for BeiGene, Genentech, Juno Therapeutics, and MEI Pharma, and scientific advisory board, consulting, or expert witness activity for Celgene Corporation, Curries, Genentech, Gilead Sciences, Janssen Pharmaceutical Products, and several other pharmaceutical and biotechnology companies.
 

[email protected]

The differences between politically left- and right-leaning individuals may have neural underpinnings, results from a new brain imaging study suggest.

Jochen Sand/Thinkstock

Investigators found that despite watching the same videos related to immigration policy, neural responses differed between liberals and conservatives.

“This divergence was strongest when the videos used language that highlighted threat, morality, and emotions, suggesting that certain words are more likely to drive polarized response,” lead researcher Yuan Chang Leong, PhD, a postdoctoral scholar in cognitive neuroscience at the University of California, Berkeley, told Medscape Medical News.

“The results suggest a neural basis for partisan biases in interpreting political messages, the effects these biases have on attitude change, and the type of language most likely to drive biased interpretations,” Leong added.

The study was published online Oct. 20 in Proceedings of the National Academy of Sciences.
 

Hardwired to disagree?

The researchers combined fMRI with semantic content analysis to investigate neural mechanisms that underlie the biased processing of political content.

They scanned 38 middle-aged men and women with liberal- or conservative-leaning immigration attitudes while the participants watched short news clips, campaign ads, and public speeches related to various immigration policies.

These policies included those that led to the United States–Mexico border wall, Deferred Action for Childhood Arrivals (DACA) protections for undocumented immigrants, the ban on refugees from majority-Muslim countries coming to the United States, and the cutting of federal funding to sanctuary cities.

After each video, participants rated on a scale of 1 to 5 how much they agreed with the general message of the video, the credibility of the information presented, and the extent to which the video made them likely to change their position and to support the policy in question.

The study revealed evidence of “neural polarization” – activity in the brain that diverges between people who hold liberal vs. conservative political views, the researchers reported.

Neural polarization was observed in the dorsomedial prefrontal cortex (DMPFC), a brain region associated with the interpretation of narrative content.

Neural polarization in this region intensified during moments in the videos that included risk-related and moral-emotional language, highlighting content features most likely to drive divergent interpretations between conservatives and liberals, they noted.

For a given individual, the closer that brain activity resembled that of the “average conservative” or “average liberal,” the more likely the person was to adopt that group’s position after watching the videos.

“We know that partisans respond differently to the same information. So in that sense, it’s not surprising to find that their brains respond differently as well,” Leong told Medscape Medical News.

“What we weren’t sure about was where in the brain we would find these differences, how neural differences were related to attitude change, and what type of content would be most likely to be associated with these differences,” he said.

Importantly, said Leong, these differences do not imply that people are hardwired to disagree. Rather, individual experiences and the media that is consumed likely contribute to neural polarization.

“If our goal is to reduce polarization and change minds, we need to think carefully about how we frame and structure political information – for example, by framing messages to appeal to the core values of the respective voter,” he said.
 

Brain stimulation to alter political perception?

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist in Newton, Mass., and executive director, Global Neuroscience Initiative Foundation, said the research “puts us one step closer to identifying how our brains interpret political information.”

The study, Lakhan noted, implicates a specific brain structure, the DMPFC, which is the “lens” in which information that gets into our brain is “viewed and acted on.”

“I trust that there will be plenty more work using a similar fMRI approach to tease out scenarios outside of immigration policy, as used in this study. Down the line, brain signatures through fMRI may be able to tell an individual’s political bent, and perhaps technologies like transcranial magnetic stimulation may be able to modulate our perceptions of political content, Shaheen said.

The research was supported by a grant from the Army Research Office. Leong and Lakhan have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

The differences between politically left- and right-leaning individuals may have neural underpinnings, results from a new brain imaging study suggest.

Jochen Sand/Thinkstock

Investigators found that despite watching the same videos related to immigration policy, neural responses differed between liberals and conservatives.

“This divergence was strongest when the videos used language that highlighted threat, morality, and emotions, suggesting that certain words are more likely to drive polarized response,” lead researcher Yuan Chang Leong, PhD, a postdoctoral scholar in cognitive neuroscience at the University of California, Berkeley, told Medscape Medical News.

“The results suggest a neural basis for partisan biases in interpreting political messages, the effects these biases have on attitude change, and the type of language most likely to drive biased interpretations,” Leong added.

The study was published online Oct. 20 in Proceedings of the National Academy of Sciences.
 

Hardwired to disagree?

The researchers combined fMRI with semantic content analysis to investigate neural mechanisms that underlie the biased processing of political content.

They scanned 38 middle-aged men and women with liberal- or conservative-leaning immigration attitudes while the participants watched short news clips, campaign ads, and public speeches related to various immigration policies.

These policies included those that led to the United States–Mexico border wall, Deferred Action for Childhood Arrivals (DACA) protections for undocumented immigrants, the ban on refugees from majority-Muslim countries coming to the United States, and the cutting of federal funding to sanctuary cities.

After each video, participants rated on a scale of 1 to 5 how much they agreed with the general message of the video, the credibility of the information presented, and the extent to which the video made them likely to change their position and to support the policy in question.

The study revealed evidence of “neural polarization” – activity in the brain that diverges between people who hold liberal vs. conservative political views, the researchers reported.

Neural polarization was observed in the dorsomedial prefrontal cortex (DMPFC), a brain region associated with the interpretation of narrative content.

Neural polarization in this region intensified during moments in the videos that included risk-related and moral-emotional language, highlighting content features most likely to drive divergent interpretations between conservatives and liberals, they noted.

For a given individual, the closer that brain activity resembled that of the “average conservative” or “average liberal,” the more likely the person was to adopt that group’s position after watching the videos.

“We know that partisans respond differently to the same information. So in that sense, it’s not surprising to find that their brains respond differently as well,” Leong told Medscape Medical News.

“What we weren’t sure about was where in the brain we would find these differences, how neural differences were related to attitude change, and what type of content would be most likely to be associated with these differences,” he said.

Importantly, said Leong, these differences do not imply that people are hardwired to disagree. Rather, individual experiences and the media that is consumed likely contribute to neural polarization.

“If our goal is to reduce polarization and change minds, we need to think carefully about how we frame and structure political information – for example, by framing messages to appeal to the core values of the respective voter,” he said.
 

Brain stimulation to alter political perception?

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist in Newton, Mass., and executive director, Global Neuroscience Initiative Foundation, said the research “puts us one step closer to identifying how our brains interpret political information.”

The study, Lakhan noted, implicates a specific brain structure, the DMPFC, which is the “lens” in which information that gets into our brain is “viewed and acted on.”

“I trust that there will be plenty more work using a similar fMRI approach to tease out scenarios outside of immigration policy, as used in this study. Down the line, brain signatures through fMRI may be able to tell an individual’s political bent, and perhaps technologies like transcranial magnetic stimulation may be able to modulate our perceptions of political content, Shaheen said.

The research was supported by a grant from the Army Research Office. Leong and Lakhan have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

The differences between politically left- and right-leaning individuals may have neural underpinnings, results from a new brain imaging study suggest.

Jochen Sand/Thinkstock

Investigators found that despite watching the same videos related to immigration policy, neural responses differed between liberals and conservatives.

“This divergence was strongest when the videos used language that highlighted threat, morality, and emotions, suggesting that certain words are more likely to drive polarized response,” lead researcher Yuan Chang Leong, PhD, a postdoctoral scholar in cognitive neuroscience at the University of California, Berkeley, told Medscape Medical News.

“The results suggest a neural basis for partisan biases in interpreting political messages, the effects these biases have on attitude change, and the type of language most likely to drive biased interpretations,” Leong added.

The study was published online Oct. 20 in Proceedings of the National Academy of Sciences.
 

Hardwired to disagree?

The researchers combined fMRI with semantic content analysis to investigate neural mechanisms that underlie the biased processing of political content.

They scanned 38 middle-aged men and women with liberal- or conservative-leaning immigration attitudes while the participants watched short news clips, campaign ads, and public speeches related to various immigration policies.

These policies included those that led to the United States–Mexico border wall, Deferred Action for Childhood Arrivals (DACA) protections for undocumented immigrants, the ban on refugees from majority-Muslim countries coming to the United States, and the cutting of federal funding to sanctuary cities.

After each video, participants rated on a scale of 1 to 5 how much they agreed with the general message of the video, the credibility of the information presented, and the extent to which the video made them likely to change their position and to support the policy in question.

The study revealed evidence of “neural polarization” – activity in the brain that diverges between people who hold liberal vs. conservative political views, the researchers reported.

Neural polarization was observed in the dorsomedial prefrontal cortex (DMPFC), a brain region associated with the interpretation of narrative content.

Neural polarization in this region intensified during moments in the videos that included risk-related and moral-emotional language, highlighting content features most likely to drive divergent interpretations between conservatives and liberals, they noted.

For a given individual, the closer that brain activity resembled that of the “average conservative” or “average liberal,” the more likely the person was to adopt that group’s position after watching the videos.

“We know that partisans respond differently to the same information. So in that sense, it’s not surprising to find that their brains respond differently as well,” Leong told Medscape Medical News.

“What we weren’t sure about was where in the brain we would find these differences, how neural differences were related to attitude change, and what type of content would be most likely to be associated with these differences,” he said.

Importantly, said Leong, these differences do not imply that people are hardwired to disagree. Rather, individual experiences and the media that is consumed likely contribute to neural polarization.

“If our goal is to reduce polarization and change minds, we need to think carefully about how we frame and structure political information – for example, by framing messages to appeal to the core values of the respective voter,” he said.
 

Brain stimulation to alter political perception?

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist in Newton, Mass., and executive director, Global Neuroscience Initiative Foundation, said the research “puts us one step closer to identifying how our brains interpret political information.”

The study, Lakhan noted, implicates a specific brain structure, the DMPFC, which is the “lens” in which information that gets into our brain is “viewed and acted on.”

“I trust that there will be plenty more work using a similar fMRI approach to tease out scenarios outside of immigration policy, as used in this study. Down the line, brain signatures through fMRI may be able to tell an individual’s political bent, and perhaps technologies like transcranial magnetic stimulation may be able to modulate our perceptions of political content, Shaheen said.

The research was supported by a grant from the Army Research Office. Leong and Lakhan have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.