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Study supports new NCCN classification for cutaneous squamous cell carcinoma
, according to new findings.
In addition, regardless of the NCCN risk group, the study found that Mohs surgery or peripheral and deep en face margin assessment (PDEMA) conferred a lower risk of developing LR, DM, and disease-related death.
“Although the NCCN included this new high-risk group in the last iteration of the guidelines, there were no studies that identified whether the high-risk group achieved the goal of identifying riskier tumors,” said senior author Emily Ruiz, MD, MPH, associate physician at the Mohs and Dermatologic Surgery Center at Brigham and Women’s Faulkner Hospital, Boston. “Based on the data in our study, the risk groups did risk stratify tumors and so clinicians can utilize the high-risk group risk factors to identify which tumors may require additional surveillance or treatment.”
The study was published online in JAMA Dermatology.
Most patients with CSCC are successfully treated with Mohs micrographic surgery or wide local excision (WLE) alone, but a subset will experience more severe and aggressive disease. While useful for prognostication, current staging systems do not incorporate patient factors or other high-risk tumor features that influence outcomes, which led to the NCCN reclassifying CSCC into low-, high-, and very high-risk groups. The NCCN guidelines also made a new recommendation that Mohs or PDEMA be the preferred method for tissue processing for high- and very-high-risk tumors, based on this new stratification.
However, these changes to the NCCN guidelines have not been validated. The goal of this study was to compare outcomes in very-high-, high-, and low-risk NCCN groups as well as comparing outcomes of CSCCs stratified by Mohs and WLE.
Dr. Ruiz and colleagues conducted a retrospective cohort study using patient data from two tertiary care academic medical centers. Their analysis included 10,196 tumors from 8,727 patients that were then stratified into low-risk (3,054 tumors [30.0%]), high-risk (6,269 tumors [61.5%]), and very-high-risk (873 tumors [8.6%]) groups.
Tumors in the very-high-risk group were more likely to have high-risk tumor and histologic features, such as large-caliber perineural invasion, large diameter, invasion beyond the subcutaneous fat or bone, poor differentiation, and lymphovascular invasion.
The authors found that, compared with the low-risk group, the high- and very-high-risk groups demonstrated a greater risk of LR (high-risk subhazard ratio, 1.99; P = .007; very-high-risk SHR, 12.66; P < .001); NM (high-risk SHR, 4.26; P = .02; very-high-risk SHR, 62.98; P < .001); DM (high-risk SHR, 2.2 × 107;P < .001; very-high-risk SHR, 6.3 × 108;P < .001); and DSD (high-risk SHR, 4.02; P = .03; very-high-risk SHR, 93.87; P < .001).
Adjusted 5-year cumulative incidence was also significantly higher in very-high- vs. high- and low-risk groups for all endpoints.
They next compared the procedures used to treat the tumors. Compared with WLE, patients treated with Mohs or PDEMA had a lower risk of LR (SHR, 0.65; P = .009), DM (SHR, 0.38; P = .02), and DSD (SHR, 0.55; P = .006).
Mohs and PDEMA have already became preferred surgical modalities for high- and very-high-risk tumors, and Dr. Ruiz pointed out that their analysis was for the entire cohort.
“We did not stratify this by risk group,” she said. “So our results do not change anything clinically at this time, but support prior studies that have found Mohs/PDEMA to have improved outcomes, compared to WLE. Further studies are needed evaluating surgical approach by risk-group.”
However, she emphasized, “our studies further validate prior evidence showing Mohs/PDEMA to have the lowest rates of recurrence and in this study, even disease-related death.”
Approached for an independent comment, Jeffrey M. Farma, MD, codirector of the melanoma and skin cancer program, and interim chair, department of surgical oncology, Fox Chase Cancer Center, Philadelphia, noted that this study supports the new reclassification of CSCC tumors by the NCCN, and confirms that the high-risk and very-high-risk tumors surely have a higher propensity for worse outcomes overall.
“That being said, the notion for type of resection and margin assessment is still an area of controversy in the dermatology, surgical oncology, and pathology community,” said Dr. Farma, who is also on the NCCN panel. “I believe we need further studies to truly understand the role of the type of resection and the pathologic evaluation play in this disease process.”
He also pointed out that it is unclear in this dataset if patients initially had any imaging to evaluate for local or regional metastatic disease. “It would be helpful to have a further understanding of which type of provider was performing the excisions, the type of excision decided upon, and if there was a standardized approach to [decide] which patients had MOHS or PDEMA and what was the surveillance for these patients both with imaging and physical examinations,” said Dr. Farma. “This data also evaluated patients over a long time period where practice patterns have evolved.”
Finally, he noted that the number of local and metastatic events subjectively seems low in this cohort. “We also do not know any information about the initial workup of the patients, patterns of recurrence, and adjuvant or palliative treatment after recurrence,” he added. “It is unclear from this manuscript how the type of resection or pathologic evaluation of margins leads to improved outcomes and further prospective studies are warranted.”
Dr. Ruiz reports reported serving as a coinvestigator and principal investigator for Regeneron Pharmaceuticals and as a coinvestigator for Merck and consulting for Checkpoint Therapeutics, BDO, and Genentech outside the submitted work. Dr. Farma has no disclosures other than the NCCN panel. The study was supported by Harvard Catalyst and the Harvard University Clinical and Translational Science Center and by Harvard University and its affiliated academic health care centers and partially supported by the Melvin Markey Discovery Fund at Cleveland Clinic Foundation.
, according to new findings.
In addition, regardless of the NCCN risk group, the study found that Mohs surgery or peripheral and deep en face margin assessment (PDEMA) conferred a lower risk of developing LR, DM, and disease-related death.
“Although the NCCN included this new high-risk group in the last iteration of the guidelines, there were no studies that identified whether the high-risk group achieved the goal of identifying riskier tumors,” said senior author Emily Ruiz, MD, MPH, associate physician at the Mohs and Dermatologic Surgery Center at Brigham and Women’s Faulkner Hospital, Boston. “Based on the data in our study, the risk groups did risk stratify tumors and so clinicians can utilize the high-risk group risk factors to identify which tumors may require additional surveillance or treatment.”
The study was published online in JAMA Dermatology.
Most patients with CSCC are successfully treated with Mohs micrographic surgery or wide local excision (WLE) alone, but a subset will experience more severe and aggressive disease. While useful for prognostication, current staging systems do not incorporate patient factors or other high-risk tumor features that influence outcomes, which led to the NCCN reclassifying CSCC into low-, high-, and very high-risk groups. The NCCN guidelines also made a new recommendation that Mohs or PDEMA be the preferred method for tissue processing for high- and very-high-risk tumors, based on this new stratification.
However, these changes to the NCCN guidelines have not been validated. The goal of this study was to compare outcomes in very-high-, high-, and low-risk NCCN groups as well as comparing outcomes of CSCCs stratified by Mohs and WLE.
Dr. Ruiz and colleagues conducted a retrospective cohort study using patient data from two tertiary care academic medical centers. Their analysis included 10,196 tumors from 8,727 patients that were then stratified into low-risk (3,054 tumors [30.0%]), high-risk (6,269 tumors [61.5%]), and very-high-risk (873 tumors [8.6%]) groups.
Tumors in the very-high-risk group were more likely to have high-risk tumor and histologic features, such as large-caliber perineural invasion, large diameter, invasion beyond the subcutaneous fat or bone, poor differentiation, and lymphovascular invasion.
The authors found that, compared with the low-risk group, the high- and very-high-risk groups demonstrated a greater risk of LR (high-risk subhazard ratio, 1.99; P = .007; very-high-risk SHR, 12.66; P < .001); NM (high-risk SHR, 4.26; P = .02; very-high-risk SHR, 62.98; P < .001); DM (high-risk SHR, 2.2 × 107;P < .001; very-high-risk SHR, 6.3 × 108;P < .001); and DSD (high-risk SHR, 4.02; P = .03; very-high-risk SHR, 93.87; P < .001).
Adjusted 5-year cumulative incidence was also significantly higher in very-high- vs. high- and low-risk groups for all endpoints.
They next compared the procedures used to treat the tumors. Compared with WLE, patients treated with Mohs or PDEMA had a lower risk of LR (SHR, 0.65; P = .009), DM (SHR, 0.38; P = .02), and DSD (SHR, 0.55; P = .006).
Mohs and PDEMA have already became preferred surgical modalities for high- and very-high-risk tumors, and Dr. Ruiz pointed out that their analysis was for the entire cohort.
“We did not stratify this by risk group,” she said. “So our results do not change anything clinically at this time, but support prior studies that have found Mohs/PDEMA to have improved outcomes, compared to WLE. Further studies are needed evaluating surgical approach by risk-group.”
However, she emphasized, “our studies further validate prior evidence showing Mohs/PDEMA to have the lowest rates of recurrence and in this study, even disease-related death.”
Approached for an independent comment, Jeffrey M. Farma, MD, codirector of the melanoma and skin cancer program, and interim chair, department of surgical oncology, Fox Chase Cancer Center, Philadelphia, noted that this study supports the new reclassification of CSCC tumors by the NCCN, and confirms that the high-risk and very-high-risk tumors surely have a higher propensity for worse outcomes overall.
“That being said, the notion for type of resection and margin assessment is still an area of controversy in the dermatology, surgical oncology, and pathology community,” said Dr. Farma, who is also on the NCCN panel. “I believe we need further studies to truly understand the role of the type of resection and the pathologic evaluation play in this disease process.”
He also pointed out that it is unclear in this dataset if patients initially had any imaging to evaluate for local or regional metastatic disease. “It would be helpful to have a further understanding of which type of provider was performing the excisions, the type of excision decided upon, and if there was a standardized approach to [decide] which patients had MOHS or PDEMA and what was the surveillance for these patients both with imaging and physical examinations,” said Dr. Farma. “This data also evaluated patients over a long time period where practice patterns have evolved.”
Finally, he noted that the number of local and metastatic events subjectively seems low in this cohort. “We also do not know any information about the initial workup of the patients, patterns of recurrence, and adjuvant or palliative treatment after recurrence,” he added. “It is unclear from this manuscript how the type of resection or pathologic evaluation of margins leads to improved outcomes and further prospective studies are warranted.”
Dr. Ruiz reports reported serving as a coinvestigator and principal investigator for Regeneron Pharmaceuticals and as a coinvestigator for Merck and consulting for Checkpoint Therapeutics, BDO, and Genentech outside the submitted work. Dr. Farma has no disclosures other than the NCCN panel. The study was supported by Harvard Catalyst and the Harvard University Clinical and Translational Science Center and by Harvard University and its affiliated academic health care centers and partially supported by the Melvin Markey Discovery Fund at Cleveland Clinic Foundation.
, according to new findings.
In addition, regardless of the NCCN risk group, the study found that Mohs surgery or peripheral and deep en face margin assessment (PDEMA) conferred a lower risk of developing LR, DM, and disease-related death.
“Although the NCCN included this new high-risk group in the last iteration of the guidelines, there were no studies that identified whether the high-risk group achieved the goal of identifying riskier tumors,” said senior author Emily Ruiz, MD, MPH, associate physician at the Mohs and Dermatologic Surgery Center at Brigham and Women’s Faulkner Hospital, Boston. “Based on the data in our study, the risk groups did risk stratify tumors and so clinicians can utilize the high-risk group risk factors to identify which tumors may require additional surveillance or treatment.”
The study was published online in JAMA Dermatology.
Most patients with CSCC are successfully treated with Mohs micrographic surgery or wide local excision (WLE) alone, but a subset will experience more severe and aggressive disease. While useful for prognostication, current staging systems do not incorporate patient factors or other high-risk tumor features that influence outcomes, which led to the NCCN reclassifying CSCC into low-, high-, and very high-risk groups. The NCCN guidelines also made a new recommendation that Mohs or PDEMA be the preferred method for tissue processing for high- and very-high-risk tumors, based on this new stratification.
However, these changes to the NCCN guidelines have not been validated. The goal of this study was to compare outcomes in very-high-, high-, and low-risk NCCN groups as well as comparing outcomes of CSCCs stratified by Mohs and WLE.
Dr. Ruiz and colleagues conducted a retrospective cohort study using patient data from two tertiary care academic medical centers. Their analysis included 10,196 tumors from 8,727 patients that were then stratified into low-risk (3,054 tumors [30.0%]), high-risk (6,269 tumors [61.5%]), and very-high-risk (873 tumors [8.6%]) groups.
Tumors in the very-high-risk group were more likely to have high-risk tumor and histologic features, such as large-caliber perineural invasion, large diameter, invasion beyond the subcutaneous fat or bone, poor differentiation, and lymphovascular invasion.
The authors found that, compared with the low-risk group, the high- and very-high-risk groups demonstrated a greater risk of LR (high-risk subhazard ratio, 1.99; P = .007; very-high-risk SHR, 12.66; P < .001); NM (high-risk SHR, 4.26; P = .02; very-high-risk SHR, 62.98; P < .001); DM (high-risk SHR, 2.2 × 107;P < .001; very-high-risk SHR, 6.3 × 108;P < .001); and DSD (high-risk SHR, 4.02; P = .03; very-high-risk SHR, 93.87; P < .001).
Adjusted 5-year cumulative incidence was also significantly higher in very-high- vs. high- and low-risk groups for all endpoints.
They next compared the procedures used to treat the tumors. Compared with WLE, patients treated with Mohs or PDEMA had a lower risk of LR (SHR, 0.65; P = .009), DM (SHR, 0.38; P = .02), and DSD (SHR, 0.55; P = .006).
Mohs and PDEMA have already became preferred surgical modalities for high- and very-high-risk tumors, and Dr. Ruiz pointed out that their analysis was for the entire cohort.
“We did not stratify this by risk group,” she said. “So our results do not change anything clinically at this time, but support prior studies that have found Mohs/PDEMA to have improved outcomes, compared to WLE. Further studies are needed evaluating surgical approach by risk-group.”
However, she emphasized, “our studies further validate prior evidence showing Mohs/PDEMA to have the lowest rates of recurrence and in this study, even disease-related death.”
Approached for an independent comment, Jeffrey M. Farma, MD, codirector of the melanoma and skin cancer program, and interim chair, department of surgical oncology, Fox Chase Cancer Center, Philadelphia, noted that this study supports the new reclassification of CSCC tumors by the NCCN, and confirms that the high-risk and very-high-risk tumors surely have a higher propensity for worse outcomes overall.
“That being said, the notion for type of resection and margin assessment is still an area of controversy in the dermatology, surgical oncology, and pathology community,” said Dr. Farma, who is also on the NCCN panel. “I believe we need further studies to truly understand the role of the type of resection and the pathologic evaluation play in this disease process.”
He also pointed out that it is unclear in this dataset if patients initially had any imaging to evaluate for local or regional metastatic disease. “It would be helpful to have a further understanding of which type of provider was performing the excisions, the type of excision decided upon, and if there was a standardized approach to [decide] which patients had MOHS or PDEMA and what was the surveillance for these patients both with imaging and physical examinations,” said Dr. Farma. “This data also evaluated patients over a long time period where practice patterns have evolved.”
Finally, he noted that the number of local and metastatic events subjectively seems low in this cohort. “We also do not know any information about the initial workup of the patients, patterns of recurrence, and adjuvant or palliative treatment after recurrence,” he added. “It is unclear from this manuscript how the type of resection or pathologic evaluation of margins leads to improved outcomes and further prospective studies are warranted.”
Dr. Ruiz reports reported serving as a coinvestigator and principal investigator for Regeneron Pharmaceuticals and as a coinvestigator for Merck and consulting for Checkpoint Therapeutics, BDO, and Genentech outside the submitted work. Dr. Farma has no disclosures other than the NCCN panel. The study was supported by Harvard Catalyst and the Harvard University Clinical and Translational Science Center and by Harvard University and its affiliated academic health care centers and partially supported by the Melvin Markey Discovery Fund at Cleveland Clinic Foundation.
FROM JAMA DERMATOLOGY
Multiprong strategy makes clinical trials less White
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT ASCO 2023
I selected a GI career path aligned with my goals
In this video, Dr. David Ramsay of Digestive Health Specialists in Winston Salem, N.C., discusses the different career paths available to fellows and early-career physicians, and why he chose to become a private practice gastroenterologist. Dr. Ramsay shares his insights into different private practice models and what physicians should consider when beginning their careers, as well as what questions to ask when trying to determine if an organization will be a good fit for their future career plans. He has no financial conflicts relative to the topics in this video.
In this video, Dr. David Ramsay of Digestive Health Specialists in Winston Salem, N.C., discusses the different career paths available to fellows and early-career physicians, and why he chose to become a private practice gastroenterologist. Dr. Ramsay shares his insights into different private practice models and what physicians should consider when beginning their careers, as well as what questions to ask when trying to determine if an organization will be a good fit for their future career plans. He has no financial conflicts relative to the topics in this video.
In this video, Dr. David Ramsay of Digestive Health Specialists in Winston Salem, N.C., discusses the different career paths available to fellows and early-career physicians, and why he chose to become a private practice gastroenterologist. Dr. Ramsay shares his insights into different private practice models and what physicians should consider when beginning their careers, as well as what questions to ask when trying to determine if an organization will be a good fit for their future career plans. He has no financial conflicts relative to the topics in this video.
CBSM phone app eases anxiety, depression in cancer patients
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
AT ASCO 2023
FDA approves talazoparib for metastatic prostate cancer
Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.
The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).
Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.
Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.
“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”
A version of this article originally appeared on Medscape.com.
Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.
The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).
Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.
Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.
“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”
A version of this article originally appeared on Medscape.com.
Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.
The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).
Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.
Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.
“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”
A version of this article originally appeared on Medscape.com.
Breast cancer family history linked to better BC survival
TOPLINE:
METHODOLOGY:
- Investigators reviewed 28,649 Swedish women diagnosed with breast cancer from 1991 to 2019.
- Overall, 5,081 patients (17.7%) had at least one female first-degree relative previously diagnosed with breast cancer.
TAKEAWAYS:
- After adjusting for demographics, tumor characteristics, and treatments, a family history of breast cancer was associated with a lower risk of breast cancer–specific death in the full cohort (hazard ratio, 0.78) and in ER-negative women (HR, 0.57) within 5 years of diagnosis, after which point the association was no longer significant.
- The lower risk of death among women with a family history could mean that these women are more motivated and likely to get screened, potentially catching tumors earlier, and may be more likely to adhere to treatment recommendations.
- However, having a family history of early-onset breast cancer (before the age of 40) was associated with a higher risk of breast cancer–specific death (HR, 1.41).
IN PRACTICE:
Although the findings are reassuring for many women with breast cancer, “genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research,” the researchers concluded.
STUDY DETAILS:
The study was led by Yuqi Zhang, PhD, of the Karolinska Institutet, Stockholm, and published in JAMA Network Open.
LIMITATIONS:
- The main analysis did not include tumor characteristics only available within the last 20 years, including ERBB2 status.
- Relatively wide confidence intervals make the association between a family history of early-onset breast cancer and higher risk of breast cancer death somewhat uncertain.
DISCLOSURES:
- The work was funded by the Swedish Cancer Society and others.
- The investigators report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Investigators reviewed 28,649 Swedish women diagnosed with breast cancer from 1991 to 2019.
- Overall, 5,081 patients (17.7%) had at least one female first-degree relative previously diagnosed with breast cancer.
TAKEAWAYS:
- After adjusting for demographics, tumor characteristics, and treatments, a family history of breast cancer was associated with a lower risk of breast cancer–specific death in the full cohort (hazard ratio, 0.78) and in ER-negative women (HR, 0.57) within 5 years of diagnosis, after which point the association was no longer significant.
- The lower risk of death among women with a family history could mean that these women are more motivated and likely to get screened, potentially catching tumors earlier, and may be more likely to adhere to treatment recommendations.
- However, having a family history of early-onset breast cancer (before the age of 40) was associated with a higher risk of breast cancer–specific death (HR, 1.41).
IN PRACTICE:
Although the findings are reassuring for many women with breast cancer, “genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research,” the researchers concluded.
STUDY DETAILS:
The study was led by Yuqi Zhang, PhD, of the Karolinska Institutet, Stockholm, and published in JAMA Network Open.
LIMITATIONS:
- The main analysis did not include tumor characteristics only available within the last 20 years, including ERBB2 status.
- Relatively wide confidence intervals make the association between a family history of early-onset breast cancer and higher risk of breast cancer death somewhat uncertain.
DISCLOSURES:
- The work was funded by the Swedish Cancer Society and others.
- The investigators report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Investigators reviewed 28,649 Swedish women diagnosed with breast cancer from 1991 to 2019.
- Overall, 5,081 patients (17.7%) had at least one female first-degree relative previously diagnosed with breast cancer.
TAKEAWAYS:
- After adjusting for demographics, tumor characteristics, and treatments, a family history of breast cancer was associated with a lower risk of breast cancer–specific death in the full cohort (hazard ratio, 0.78) and in ER-negative women (HR, 0.57) within 5 years of diagnosis, after which point the association was no longer significant.
- The lower risk of death among women with a family history could mean that these women are more motivated and likely to get screened, potentially catching tumors earlier, and may be more likely to adhere to treatment recommendations.
- However, having a family history of early-onset breast cancer (before the age of 40) was associated with a higher risk of breast cancer–specific death (HR, 1.41).
IN PRACTICE:
Although the findings are reassuring for many women with breast cancer, “genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research,” the researchers concluded.
STUDY DETAILS:
The study was led by Yuqi Zhang, PhD, of the Karolinska Institutet, Stockholm, and published in JAMA Network Open.
LIMITATIONS:
- The main analysis did not include tumor characteristics only available within the last 20 years, including ERBB2 status.
- Relatively wide confidence intervals make the association between a family history of early-onset breast cancer and higher risk of breast cancer death somewhat uncertain.
DISCLOSURES:
- The work was funded by the Swedish Cancer Society and others.
- The investigators report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
T-DXd active in many solid tumors; ‘shift in thinking’
CHICAGO – Trastuzumab deruxtecan (T-DXd) (Enhertu) already has proven efficacy against HER2-expressing metastatic breast, gastroesophageal, and lung cancers.
including malignancies of the cervix, endometrium, ovaries, bladder, and other sites.
The findings come from the ongoing DESTINY-PanTumor02 trial. Among 267 patients with solid tumors at various organ sites, the investigator-assessed objective response rate among all patients was 37.1%, and ranged from as high as 57.5% for patients with endometrial cancers to as low as 4% for patients with pancreatic cancer, reported Funda Meric-Bernstam, MD, from the University of Texas MD Anderson Cancer Center, Houston.
For patients with tumors that had HER2 immunohistochemistry (IHC) scores of 3+, the highest level of HER2 expression, the overall response rate was 61.3%..
The responses were also durable, with a median duration of 11.8 months among all patients and 22.1 months among patients with IHC 3+ scores.
“Our data to date showed that T-DXd had clinically meaningful activity across a variety of tumor types,” she said in a briefing held prior to her presentation of the data at the annual meeting of the American Society of Clinical Oncology.
“HER2 expression has been around a long time. We think about this all the time in breast cancer and drugs are approved there, but HER2 is expressed in other tumors as well, and that really represents an unmet need, because we have limited options in this situation” commented ASCO expert Bradley Alexander McGregor, MD, from the Dana-Farber Cancer Institute, Boston, an invited discussant at the briefing.
“Aside from pancreatic cancer we saw really, really encouraging results with no new safety signals, so while early I think this really exciting and represents a shift in how we think about cancer care,” he added.
After the presentation, invited discussant Kohei Shitara, MD, of National Cancer Center Hospital East, Kashiwa, Japan, said that he agrees with authors that T-DXd is a potential new treatment option for patients with HER2-expressing solid tumors, and that the evidence suggests the potential for further tumor-agnostic development of the agent.
He cautioned, however, that there is a lack of concordance between local and central assessment of HER2 IHC, and that quality assurance will be required to ensure that the HER2 status of solid tumors is accurately characterized.
At a press briefing, Dr. Meric-Bernstam was asked how she envisioned using T-DXd in therapy for various HER2-expressing tumors.
“I think the activity we’ve seen is quite compelling, and one hopes that eventually this will be a drug that’s accessible for patients that are HER2-expressing across tumor types. Clearly, the activity is very compelling in some of the diseases to think about doing studies for earlier lines,” she said.
“The data indicate that there is tumor-agnostic activity across the board,” she said, but noted that tumors with epithelial components such as ovarian and breast cancers appear to have the highest responses to T-DXd therapy.
Briefing moderator Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, asked Dr. McGregor whether, in the light of this new data, oncologists should test more patients for HER2 expression.
“We have some cancers where we know HER2 expression is there. I think the good thing about HER2 testing is that it’s an IHC test, so this is something that can be easily done in local pathology [labs],” he said. As more evidence mounts of potential benefit of T-DXd in HER2 expressing tumors, clinicians will need to consider more routine HER2 testing.
A rendezvous with DESTINY
The DESTINY-PanTumor02 trial is a phase 2, open-label, multicenter study looking at T-DXd in patients with advanced solid tumors who are not eligible for therapy with curative intent.
All patients had disease progression after at least two prior lines of therapy, and had tumors with HER2 expression of IHC 3+ or 2+ either by local or central testing. Patients were allowed to have previously received HER2-targeting therapy. Patients also had to have good performance status (Eastern Cooperative Oncology Group/World Health Organization performance status 0 or 1).
The investigators planned to enroll 40 patients in each cohort, including patients with cervical, endometrial, ovarian, biliary tract, pancreatic, or bladder cancers, as well those with other tumors expressing HER2 who were not included in the other cohorts.
Under the protocol, cohorts in which none of the first 15 patients had objective responses would be closed, as happened with the pancreatic cancer cohort.
At a median follow-up of 9.7 months, an objective response was seen in 99 patients out of the 267 in the entire study population (ORR, 37.1%). This ORR consisted of 15 complete responses and 84 partial responses. An additional 123 patients had stable disease.
An analysis of ORR by HER2 expression showed that IHC 3+ expressing tumors had rates ranging from 84.6% in endometrial cancers, 75% in cervical cancer, 63.6% in ovarian cancers, and 56.3% in bladder cancers, down to zero in IHC 3+ expressing pancreatic cancer.
The T-DXd safety profile was consistent with that seen in other clinical trials, with most common adverse events being nausea, fatigue, neutropenia, anemia, diarrhea, and thrombocytopenia. There were 20 cases of interstitial lung disease, one of which was fatal.
The trial is ongoing, and investigators plan to report overall survival and progression-free survival results with additional follow-up.
DESTINY-PanTumor02 is funded by Daiichi Sankyo. Dr. Meric-Bernstam disclosed a consulting/advisory role with multiple pharmaceutical companies, research funding to her institution from Daiichi Sankyo and others, and travel expenses from ESMO and EORTC. Dr. McGregor disclosed a consulting/advisory role and institutional research funding with multiple companies, not including the study’s funder. Dr. Gralow disclosed a consulting or advisory role with Genentech and Roche.
A version of this article first appeared on Medscape.com.
CHICAGO – Trastuzumab deruxtecan (T-DXd) (Enhertu) already has proven efficacy against HER2-expressing metastatic breast, gastroesophageal, and lung cancers.
including malignancies of the cervix, endometrium, ovaries, bladder, and other sites.
The findings come from the ongoing DESTINY-PanTumor02 trial. Among 267 patients with solid tumors at various organ sites, the investigator-assessed objective response rate among all patients was 37.1%, and ranged from as high as 57.5% for patients with endometrial cancers to as low as 4% for patients with pancreatic cancer, reported Funda Meric-Bernstam, MD, from the University of Texas MD Anderson Cancer Center, Houston.
For patients with tumors that had HER2 immunohistochemistry (IHC) scores of 3+, the highest level of HER2 expression, the overall response rate was 61.3%..
The responses were also durable, with a median duration of 11.8 months among all patients and 22.1 months among patients with IHC 3+ scores.
“Our data to date showed that T-DXd had clinically meaningful activity across a variety of tumor types,” she said in a briefing held prior to her presentation of the data at the annual meeting of the American Society of Clinical Oncology.
“HER2 expression has been around a long time. We think about this all the time in breast cancer and drugs are approved there, but HER2 is expressed in other tumors as well, and that really represents an unmet need, because we have limited options in this situation” commented ASCO expert Bradley Alexander McGregor, MD, from the Dana-Farber Cancer Institute, Boston, an invited discussant at the briefing.
“Aside from pancreatic cancer we saw really, really encouraging results with no new safety signals, so while early I think this really exciting and represents a shift in how we think about cancer care,” he added.
After the presentation, invited discussant Kohei Shitara, MD, of National Cancer Center Hospital East, Kashiwa, Japan, said that he agrees with authors that T-DXd is a potential new treatment option for patients with HER2-expressing solid tumors, and that the evidence suggests the potential for further tumor-agnostic development of the agent.
He cautioned, however, that there is a lack of concordance between local and central assessment of HER2 IHC, and that quality assurance will be required to ensure that the HER2 status of solid tumors is accurately characterized.
At a press briefing, Dr. Meric-Bernstam was asked how she envisioned using T-DXd in therapy for various HER2-expressing tumors.
“I think the activity we’ve seen is quite compelling, and one hopes that eventually this will be a drug that’s accessible for patients that are HER2-expressing across tumor types. Clearly, the activity is very compelling in some of the diseases to think about doing studies for earlier lines,” she said.
“The data indicate that there is tumor-agnostic activity across the board,” she said, but noted that tumors with epithelial components such as ovarian and breast cancers appear to have the highest responses to T-DXd therapy.
Briefing moderator Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, asked Dr. McGregor whether, in the light of this new data, oncologists should test more patients for HER2 expression.
“We have some cancers where we know HER2 expression is there. I think the good thing about HER2 testing is that it’s an IHC test, so this is something that can be easily done in local pathology [labs],” he said. As more evidence mounts of potential benefit of T-DXd in HER2 expressing tumors, clinicians will need to consider more routine HER2 testing.
A rendezvous with DESTINY
The DESTINY-PanTumor02 trial is a phase 2, open-label, multicenter study looking at T-DXd in patients with advanced solid tumors who are not eligible for therapy with curative intent.
All patients had disease progression after at least two prior lines of therapy, and had tumors with HER2 expression of IHC 3+ or 2+ either by local or central testing. Patients were allowed to have previously received HER2-targeting therapy. Patients also had to have good performance status (Eastern Cooperative Oncology Group/World Health Organization performance status 0 or 1).
The investigators planned to enroll 40 patients in each cohort, including patients with cervical, endometrial, ovarian, biliary tract, pancreatic, or bladder cancers, as well those with other tumors expressing HER2 who were not included in the other cohorts.
Under the protocol, cohorts in which none of the first 15 patients had objective responses would be closed, as happened with the pancreatic cancer cohort.
At a median follow-up of 9.7 months, an objective response was seen in 99 patients out of the 267 in the entire study population (ORR, 37.1%). This ORR consisted of 15 complete responses and 84 partial responses. An additional 123 patients had stable disease.
An analysis of ORR by HER2 expression showed that IHC 3+ expressing tumors had rates ranging from 84.6% in endometrial cancers, 75% in cervical cancer, 63.6% in ovarian cancers, and 56.3% in bladder cancers, down to zero in IHC 3+ expressing pancreatic cancer.
The T-DXd safety profile was consistent with that seen in other clinical trials, with most common adverse events being nausea, fatigue, neutropenia, anemia, diarrhea, and thrombocytopenia. There were 20 cases of interstitial lung disease, one of which was fatal.
The trial is ongoing, and investigators plan to report overall survival and progression-free survival results with additional follow-up.
DESTINY-PanTumor02 is funded by Daiichi Sankyo. Dr. Meric-Bernstam disclosed a consulting/advisory role with multiple pharmaceutical companies, research funding to her institution from Daiichi Sankyo and others, and travel expenses from ESMO and EORTC. Dr. McGregor disclosed a consulting/advisory role and institutional research funding with multiple companies, not including the study’s funder. Dr. Gralow disclosed a consulting or advisory role with Genentech and Roche.
A version of this article first appeared on Medscape.com.
CHICAGO – Trastuzumab deruxtecan (T-DXd) (Enhertu) already has proven efficacy against HER2-expressing metastatic breast, gastroesophageal, and lung cancers.
including malignancies of the cervix, endometrium, ovaries, bladder, and other sites.
The findings come from the ongoing DESTINY-PanTumor02 trial. Among 267 patients with solid tumors at various organ sites, the investigator-assessed objective response rate among all patients was 37.1%, and ranged from as high as 57.5% for patients with endometrial cancers to as low as 4% for patients with pancreatic cancer, reported Funda Meric-Bernstam, MD, from the University of Texas MD Anderson Cancer Center, Houston.
For patients with tumors that had HER2 immunohistochemistry (IHC) scores of 3+, the highest level of HER2 expression, the overall response rate was 61.3%..
The responses were also durable, with a median duration of 11.8 months among all patients and 22.1 months among patients with IHC 3+ scores.
“Our data to date showed that T-DXd had clinically meaningful activity across a variety of tumor types,” she said in a briefing held prior to her presentation of the data at the annual meeting of the American Society of Clinical Oncology.
“HER2 expression has been around a long time. We think about this all the time in breast cancer and drugs are approved there, but HER2 is expressed in other tumors as well, and that really represents an unmet need, because we have limited options in this situation” commented ASCO expert Bradley Alexander McGregor, MD, from the Dana-Farber Cancer Institute, Boston, an invited discussant at the briefing.
“Aside from pancreatic cancer we saw really, really encouraging results with no new safety signals, so while early I think this really exciting and represents a shift in how we think about cancer care,” he added.
After the presentation, invited discussant Kohei Shitara, MD, of National Cancer Center Hospital East, Kashiwa, Japan, said that he agrees with authors that T-DXd is a potential new treatment option for patients with HER2-expressing solid tumors, and that the evidence suggests the potential for further tumor-agnostic development of the agent.
He cautioned, however, that there is a lack of concordance between local and central assessment of HER2 IHC, and that quality assurance will be required to ensure that the HER2 status of solid tumors is accurately characterized.
At a press briefing, Dr. Meric-Bernstam was asked how she envisioned using T-DXd in therapy for various HER2-expressing tumors.
“I think the activity we’ve seen is quite compelling, and one hopes that eventually this will be a drug that’s accessible for patients that are HER2-expressing across tumor types. Clearly, the activity is very compelling in some of the diseases to think about doing studies for earlier lines,” she said.
“The data indicate that there is tumor-agnostic activity across the board,” she said, but noted that tumors with epithelial components such as ovarian and breast cancers appear to have the highest responses to T-DXd therapy.
Briefing moderator Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, asked Dr. McGregor whether, in the light of this new data, oncologists should test more patients for HER2 expression.
“We have some cancers where we know HER2 expression is there. I think the good thing about HER2 testing is that it’s an IHC test, so this is something that can be easily done in local pathology [labs],” he said. As more evidence mounts of potential benefit of T-DXd in HER2 expressing tumors, clinicians will need to consider more routine HER2 testing.
A rendezvous with DESTINY
The DESTINY-PanTumor02 trial is a phase 2, open-label, multicenter study looking at T-DXd in patients with advanced solid tumors who are not eligible for therapy with curative intent.
All patients had disease progression after at least two prior lines of therapy, and had tumors with HER2 expression of IHC 3+ or 2+ either by local or central testing. Patients were allowed to have previously received HER2-targeting therapy. Patients also had to have good performance status (Eastern Cooperative Oncology Group/World Health Organization performance status 0 or 1).
The investigators planned to enroll 40 patients in each cohort, including patients with cervical, endometrial, ovarian, biliary tract, pancreatic, or bladder cancers, as well those with other tumors expressing HER2 who were not included in the other cohorts.
Under the protocol, cohorts in which none of the first 15 patients had objective responses would be closed, as happened with the pancreatic cancer cohort.
At a median follow-up of 9.7 months, an objective response was seen in 99 patients out of the 267 in the entire study population (ORR, 37.1%). This ORR consisted of 15 complete responses and 84 partial responses. An additional 123 patients had stable disease.
An analysis of ORR by HER2 expression showed that IHC 3+ expressing tumors had rates ranging from 84.6% in endometrial cancers, 75% in cervical cancer, 63.6% in ovarian cancers, and 56.3% in bladder cancers, down to zero in IHC 3+ expressing pancreatic cancer.
The T-DXd safety profile was consistent with that seen in other clinical trials, with most common adverse events being nausea, fatigue, neutropenia, anemia, diarrhea, and thrombocytopenia. There were 20 cases of interstitial lung disease, one of which was fatal.
The trial is ongoing, and investigators plan to report overall survival and progression-free survival results with additional follow-up.
DESTINY-PanTumor02 is funded by Daiichi Sankyo. Dr. Meric-Bernstam disclosed a consulting/advisory role with multiple pharmaceutical companies, research funding to her institution from Daiichi Sankyo and others, and travel expenses from ESMO and EORTC. Dr. McGregor disclosed a consulting/advisory role and institutional research funding with multiple companies, not including the study’s funder. Dr. Gralow disclosed a consulting or advisory role with Genentech and Roche.
A version of this article first appeared on Medscape.com.
AT ASCO 2023
Comorbid respiratory disease key predictor of NTM-PD
(NTM-PD), data from a systematic review of 99 studies indicate.
NTM-PD is frequently underdiagnosed, and data on specific risk factors are lacking, especially for high-risk individuals with preexisting respiratory diseases, wrote Michael R. Loebinger, PhD, of Imperial College London, and colleagues.
“NTM-PD can be a substantial burden for patients, contributing to lung function decline and reduced health-related quality of life, and is associated with significant morbidity and mortality,” they said.
In a study published in the journal Chest, the researchers identified 99 studies published between 2011 and 2021. Of these, 24 reported an association between risk factors and NTM-PD among patients with respiratory disease compared with patients without NTM-PD and with healthy control persons without NTM-PD; these studies were included in the meta-analysis.
Overall, comorbid respiratory disease was significantly associated with an increased risk of NTM-PD, with odds ratios ranging from 4.15 for asthma to 21.43 for bronchiectasis. Other conditions significantly associated with NTM-PD risk included history of tuberculosis (odds ratio, 12.69), interstitial lung disease (OR, 6.39), and chronic obstructive pulmonary disease (COPD) (OR, 6.63).
Other factors associated with increased NTM-PD risk included inhaled corticosteroids (OR, 4.46), oral corticosteroids (OR, 3.37), and other immunosuppressants (OR, 2.60). Additional risk factors were use of anti–tumor necrosis factor-alpha for rheumatoid arthritis (OR, 2.13), solid tumors (OR, 4.66), current pneumonia (OR, 5.54), cardiovascular disease (OR, 1.73), and low body mass index (OR, 3.04).
Additional marginal or nonsignificant associations with NTM-PD risk were found for lung function, diabetes, renal disease, cancer, healthy weight, and infection with either Pseudomonas aeruginosa or Staphylococcus aureus.
Possible protective factors, though not significant, included increasing or high BMI and long-term macrolide use.
Bronchiectasis, which is associated with the highest risk of NTM-PD, was assessed in four studies. It was evaluated less frequently because it was often considered a reason for study exclusion, the researchers wrote in their discussion.
“However, many studies report high numbers of patients with nodular bronchiectatic NTM-PD and is suggested to be almost universal in patients with noncavitary NTM-PD,” they said.
The most common risk factors for NTM-PD in the included studies were the use of immunosuppressants, female sex, COPD comorbidity, and history of suspected tuberculosis.
The findings were limited by several factors, including the high level of heterogeneity among the included studies, the lack of data on attributable risk, and inconsistent definitions of NTM-PD, the researchers noted. However, the results may be useful for highlighting risk factors that could be used to identify high-risk patients and to promote early diagnosis and treatment, they said. In addition, long-term studies are needed regarding the impact of multiple potential risk factors on individual risk for NTM-PD among patients with respiratory disease, they concluded.
The study was supported by Insmed BV. Dr. Loebinger has relationships with Insmed, AstraZeneca, Chiesi, Savara, Parion, Zambon, 30T, Electromed, Recode, AN2 Therapeutics, and Armata.
A version of this article first appeared on Medscape.com.
(NTM-PD), data from a systematic review of 99 studies indicate.
NTM-PD is frequently underdiagnosed, and data on specific risk factors are lacking, especially for high-risk individuals with preexisting respiratory diseases, wrote Michael R. Loebinger, PhD, of Imperial College London, and colleagues.
“NTM-PD can be a substantial burden for patients, contributing to lung function decline and reduced health-related quality of life, and is associated with significant morbidity and mortality,” they said.
In a study published in the journal Chest, the researchers identified 99 studies published between 2011 and 2021. Of these, 24 reported an association between risk factors and NTM-PD among patients with respiratory disease compared with patients without NTM-PD and with healthy control persons without NTM-PD; these studies were included in the meta-analysis.
Overall, comorbid respiratory disease was significantly associated with an increased risk of NTM-PD, with odds ratios ranging from 4.15 for asthma to 21.43 for bronchiectasis. Other conditions significantly associated with NTM-PD risk included history of tuberculosis (odds ratio, 12.69), interstitial lung disease (OR, 6.39), and chronic obstructive pulmonary disease (COPD) (OR, 6.63).
Other factors associated with increased NTM-PD risk included inhaled corticosteroids (OR, 4.46), oral corticosteroids (OR, 3.37), and other immunosuppressants (OR, 2.60). Additional risk factors were use of anti–tumor necrosis factor-alpha for rheumatoid arthritis (OR, 2.13), solid tumors (OR, 4.66), current pneumonia (OR, 5.54), cardiovascular disease (OR, 1.73), and low body mass index (OR, 3.04).
Additional marginal or nonsignificant associations with NTM-PD risk were found for lung function, diabetes, renal disease, cancer, healthy weight, and infection with either Pseudomonas aeruginosa or Staphylococcus aureus.
Possible protective factors, though not significant, included increasing or high BMI and long-term macrolide use.
Bronchiectasis, which is associated with the highest risk of NTM-PD, was assessed in four studies. It was evaluated less frequently because it was often considered a reason for study exclusion, the researchers wrote in their discussion.
“However, many studies report high numbers of patients with nodular bronchiectatic NTM-PD and is suggested to be almost universal in patients with noncavitary NTM-PD,” they said.
The most common risk factors for NTM-PD in the included studies were the use of immunosuppressants, female sex, COPD comorbidity, and history of suspected tuberculosis.
The findings were limited by several factors, including the high level of heterogeneity among the included studies, the lack of data on attributable risk, and inconsistent definitions of NTM-PD, the researchers noted. However, the results may be useful for highlighting risk factors that could be used to identify high-risk patients and to promote early diagnosis and treatment, they said. In addition, long-term studies are needed regarding the impact of multiple potential risk factors on individual risk for NTM-PD among patients with respiratory disease, they concluded.
The study was supported by Insmed BV. Dr. Loebinger has relationships with Insmed, AstraZeneca, Chiesi, Savara, Parion, Zambon, 30T, Electromed, Recode, AN2 Therapeutics, and Armata.
A version of this article first appeared on Medscape.com.
(NTM-PD), data from a systematic review of 99 studies indicate.
NTM-PD is frequently underdiagnosed, and data on specific risk factors are lacking, especially for high-risk individuals with preexisting respiratory diseases, wrote Michael R. Loebinger, PhD, of Imperial College London, and colleagues.
“NTM-PD can be a substantial burden for patients, contributing to lung function decline and reduced health-related quality of life, and is associated with significant morbidity and mortality,” they said.
In a study published in the journal Chest, the researchers identified 99 studies published between 2011 and 2021. Of these, 24 reported an association between risk factors and NTM-PD among patients with respiratory disease compared with patients without NTM-PD and with healthy control persons without NTM-PD; these studies were included in the meta-analysis.
Overall, comorbid respiratory disease was significantly associated with an increased risk of NTM-PD, with odds ratios ranging from 4.15 for asthma to 21.43 for bronchiectasis. Other conditions significantly associated with NTM-PD risk included history of tuberculosis (odds ratio, 12.69), interstitial lung disease (OR, 6.39), and chronic obstructive pulmonary disease (COPD) (OR, 6.63).
Other factors associated with increased NTM-PD risk included inhaled corticosteroids (OR, 4.46), oral corticosteroids (OR, 3.37), and other immunosuppressants (OR, 2.60). Additional risk factors were use of anti–tumor necrosis factor-alpha for rheumatoid arthritis (OR, 2.13), solid tumors (OR, 4.66), current pneumonia (OR, 5.54), cardiovascular disease (OR, 1.73), and low body mass index (OR, 3.04).
Additional marginal or nonsignificant associations with NTM-PD risk were found for lung function, diabetes, renal disease, cancer, healthy weight, and infection with either Pseudomonas aeruginosa or Staphylococcus aureus.
Possible protective factors, though not significant, included increasing or high BMI and long-term macrolide use.
Bronchiectasis, which is associated with the highest risk of NTM-PD, was assessed in four studies. It was evaluated less frequently because it was often considered a reason for study exclusion, the researchers wrote in their discussion.
“However, many studies report high numbers of patients with nodular bronchiectatic NTM-PD and is suggested to be almost universal in patients with noncavitary NTM-PD,” they said.
The most common risk factors for NTM-PD in the included studies were the use of immunosuppressants, female sex, COPD comorbidity, and history of suspected tuberculosis.
The findings were limited by several factors, including the high level of heterogeneity among the included studies, the lack of data on attributable risk, and inconsistent definitions of NTM-PD, the researchers noted. However, the results may be useful for highlighting risk factors that could be used to identify high-risk patients and to promote early diagnosis and treatment, they said. In addition, long-term studies are needed regarding the impact of multiple potential risk factors on individual risk for NTM-PD among patients with respiratory disease, they concluded.
The study was supported by Insmed BV. Dr. Loebinger has relationships with Insmed, AstraZeneca, Chiesi, Savara, Parion, Zambon, 30T, Electromed, Recode, AN2 Therapeutics, and Armata.
A version of this article first appeared on Medscape.com.
Does ‘skeletal age’ describe fracture impact on mortality?
Thach Tran, MD, and colleagues introduced the concept of “skeletal age” in a recently published paper that aims to incorporate the impact of fragility, or low trauma, fractures – which can occur in patients with osteoporosis – on mortality risk.
They defined “skeletal age” as the age of the skeleton following a fragility fracture. This is calculated as the chronological age of the individual plus the number of years of “life lost” as a consequence of the specific fracture.
The risk for premature death following fragility fractures is concerning, with 22%-58% of patients with hip fracture dying within a year (Brauer et al.; Rapp et al.). Thus, it’s important to treat osteoporosis in a timely fashion to reduce the risk for such fractures and the excess mortality risk associated with them.
Implementation and uptake of such treatment, however, either before or after a fragility fracture, is far from optimal (Solomon et al). This may be because patients don’t fully understand the consequence of such a fracture, and outcomes measures currently in use (such as relative risk or hazard of mortality) are difficult to communicate to patients.
In the recent paper by Dr. Tran and colleagues, the authors examined the association between fractures and mortality based on sex, age, associated comorbidities, and fracture site. They pooled this information to create a “skeletal age” for each fracture site, using data from the Danish National Hospital Discharge Registry, which documents fractures and related mortality for all Danish people.
They examined mortality over a period of at least 2 years following a fragility fracture in individuals aged 50 or older, and reported that occurrence of any fragility fracture is associated with a 30%-45% increased risk for death, with the highest risk noted for hip and femur fractures (twofold increase). Fractures of the pelvis, vertebrae, humerus, ribs, clavicle, and lower leg were also associated with increased mortality risk, but no increase was seen with fractures of the forearm, knee, ankle, hand, or foot.
The number of years of life lost at any age depending on the fracture site is represented as a linear graph of skeletal age for any chronological age, for specific fracture sites, separated by sex.
For example, the skeletal age of a 50-year-old man who has a hip fracture is 57 years (7 years of life lost as a consequence of the fracture), while that for a 70-year-old man with the same fracture is 75 years (5 years of life lost because of the fracture). Similarly, the skeletal age of a 50-year-old man with a fracture of the pelvis, femur, vertebrae, and humerus is 55 years (5 years of life lost). Fractures of the lower leg, humerus, and clavicle lead to fewer lost years of life.
The authors are to be commended for creating a simple strategy to quantify mortality risk following low-impact or fragility fractures in older individuals; this could enable providers to communicate the importance of osteoporosis treatment more effectively to patients on the basis of their skeletal age, and for patients to better understand this information.
The study design appears reasonably robust as the authors considered many factors that might affect mortality risk, such as sex, age, and comorbidities, and the results are based on information from a very large number of people – 1.6 million.
However, there’s a major issue with the concept of “skeletal age” as proposed by Dr. Tran and colleagues. The term is already in use and defines the maturity of bones in children and adolescents, also called “bone age” (Greulich and Pyle 1959; Skeletal Age, Radiology Key). This is a real oversight and could cause confusion in interpreting “skeletal age.”
Skeletal age as currently defined in children and adolescents is influenced by chronological age, exposure to certain hormones, nutritional deficiencies, and systemic diseases, and is a predictor of adult height based on the skeletal age and current height. This concept is completely different from that being proposed by the authors in this paper. Dr. Tran and colleagues (and the reviewers of this paper) are probably not familiar with the use of the terminology in youth, which is a major oversight; they should consider changing the terminology given this overlap.
Further, fragility fractures can occur from osteoporosis at any age, and this study doesn’t provide information regarding years of life lost from occurrence of fragility fractures at younger ages, or the age at which mortality risk starts to increase (as the study was performed only in those aged 50 or older).
While the study takes into account general comorbidities in developing the model to define years of life lost, it doesn’t account for other factors that can influence fracture risk, such as lifestyle factors, activity level, and genetic risk (family history of osteoporosis, for example). Of note, the impact of additional fractures isn’t considered either and should be factored into future investigations.
Overall, the study is robust and important and provides valuable information regarding mortality risk from a fragility fracture in older people. However, there are some flaws that need to be considered and addressed, the most serious of which is that the term “skeletal age” has been in existence for decades, applied to a much younger age group, and its implications are completely different from those being proposed by the authors here.
A version of this article first appeared on Medscape.com.
Thach Tran, MD, and colleagues introduced the concept of “skeletal age” in a recently published paper that aims to incorporate the impact of fragility, or low trauma, fractures – which can occur in patients with osteoporosis – on mortality risk.
They defined “skeletal age” as the age of the skeleton following a fragility fracture. This is calculated as the chronological age of the individual plus the number of years of “life lost” as a consequence of the specific fracture.
The risk for premature death following fragility fractures is concerning, with 22%-58% of patients with hip fracture dying within a year (Brauer et al.; Rapp et al.). Thus, it’s important to treat osteoporosis in a timely fashion to reduce the risk for such fractures and the excess mortality risk associated with them.
Implementation and uptake of such treatment, however, either before or after a fragility fracture, is far from optimal (Solomon et al). This may be because patients don’t fully understand the consequence of such a fracture, and outcomes measures currently in use (such as relative risk or hazard of mortality) are difficult to communicate to patients.
In the recent paper by Dr. Tran and colleagues, the authors examined the association between fractures and mortality based on sex, age, associated comorbidities, and fracture site. They pooled this information to create a “skeletal age” for each fracture site, using data from the Danish National Hospital Discharge Registry, which documents fractures and related mortality for all Danish people.
They examined mortality over a period of at least 2 years following a fragility fracture in individuals aged 50 or older, and reported that occurrence of any fragility fracture is associated with a 30%-45% increased risk for death, with the highest risk noted for hip and femur fractures (twofold increase). Fractures of the pelvis, vertebrae, humerus, ribs, clavicle, and lower leg were also associated with increased mortality risk, but no increase was seen with fractures of the forearm, knee, ankle, hand, or foot.
The number of years of life lost at any age depending on the fracture site is represented as a linear graph of skeletal age for any chronological age, for specific fracture sites, separated by sex.
For example, the skeletal age of a 50-year-old man who has a hip fracture is 57 years (7 years of life lost as a consequence of the fracture), while that for a 70-year-old man with the same fracture is 75 years (5 years of life lost because of the fracture). Similarly, the skeletal age of a 50-year-old man with a fracture of the pelvis, femur, vertebrae, and humerus is 55 years (5 years of life lost). Fractures of the lower leg, humerus, and clavicle lead to fewer lost years of life.
The authors are to be commended for creating a simple strategy to quantify mortality risk following low-impact or fragility fractures in older individuals; this could enable providers to communicate the importance of osteoporosis treatment more effectively to patients on the basis of their skeletal age, and for patients to better understand this information.
The study design appears reasonably robust as the authors considered many factors that might affect mortality risk, such as sex, age, and comorbidities, and the results are based on information from a very large number of people – 1.6 million.
However, there’s a major issue with the concept of “skeletal age” as proposed by Dr. Tran and colleagues. The term is already in use and defines the maturity of bones in children and adolescents, also called “bone age” (Greulich and Pyle 1959; Skeletal Age, Radiology Key). This is a real oversight and could cause confusion in interpreting “skeletal age.”
Skeletal age as currently defined in children and adolescents is influenced by chronological age, exposure to certain hormones, nutritional deficiencies, and systemic diseases, and is a predictor of adult height based on the skeletal age and current height. This concept is completely different from that being proposed by the authors in this paper. Dr. Tran and colleagues (and the reviewers of this paper) are probably not familiar with the use of the terminology in youth, which is a major oversight; they should consider changing the terminology given this overlap.
Further, fragility fractures can occur from osteoporosis at any age, and this study doesn’t provide information regarding years of life lost from occurrence of fragility fractures at younger ages, or the age at which mortality risk starts to increase (as the study was performed only in those aged 50 or older).
While the study takes into account general comorbidities in developing the model to define years of life lost, it doesn’t account for other factors that can influence fracture risk, such as lifestyle factors, activity level, and genetic risk (family history of osteoporosis, for example). Of note, the impact of additional fractures isn’t considered either and should be factored into future investigations.
Overall, the study is robust and important and provides valuable information regarding mortality risk from a fragility fracture in older people. However, there are some flaws that need to be considered and addressed, the most serious of which is that the term “skeletal age” has been in existence for decades, applied to a much younger age group, and its implications are completely different from those being proposed by the authors here.
A version of this article first appeared on Medscape.com.
Thach Tran, MD, and colleagues introduced the concept of “skeletal age” in a recently published paper that aims to incorporate the impact of fragility, or low trauma, fractures – which can occur in patients with osteoporosis – on mortality risk.
They defined “skeletal age” as the age of the skeleton following a fragility fracture. This is calculated as the chronological age of the individual plus the number of years of “life lost” as a consequence of the specific fracture.
The risk for premature death following fragility fractures is concerning, with 22%-58% of patients with hip fracture dying within a year (Brauer et al.; Rapp et al.). Thus, it’s important to treat osteoporosis in a timely fashion to reduce the risk for such fractures and the excess mortality risk associated with them.
Implementation and uptake of such treatment, however, either before or after a fragility fracture, is far from optimal (Solomon et al). This may be because patients don’t fully understand the consequence of such a fracture, and outcomes measures currently in use (such as relative risk or hazard of mortality) are difficult to communicate to patients.
In the recent paper by Dr. Tran and colleagues, the authors examined the association between fractures and mortality based on sex, age, associated comorbidities, and fracture site. They pooled this information to create a “skeletal age” for each fracture site, using data from the Danish National Hospital Discharge Registry, which documents fractures and related mortality for all Danish people.
They examined mortality over a period of at least 2 years following a fragility fracture in individuals aged 50 or older, and reported that occurrence of any fragility fracture is associated with a 30%-45% increased risk for death, with the highest risk noted for hip and femur fractures (twofold increase). Fractures of the pelvis, vertebrae, humerus, ribs, clavicle, and lower leg were also associated with increased mortality risk, but no increase was seen with fractures of the forearm, knee, ankle, hand, or foot.
The number of years of life lost at any age depending on the fracture site is represented as a linear graph of skeletal age for any chronological age, for specific fracture sites, separated by sex.
For example, the skeletal age of a 50-year-old man who has a hip fracture is 57 years (7 years of life lost as a consequence of the fracture), while that for a 70-year-old man with the same fracture is 75 years (5 years of life lost because of the fracture). Similarly, the skeletal age of a 50-year-old man with a fracture of the pelvis, femur, vertebrae, and humerus is 55 years (5 years of life lost). Fractures of the lower leg, humerus, and clavicle lead to fewer lost years of life.
The authors are to be commended for creating a simple strategy to quantify mortality risk following low-impact or fragility fractures in older individuals; this could enable providers to communicate the importance of osteoporosis treatment more effectively to patients on the basis of their skeletal age, and for patients to better understand this information.
The study design appears reasonably robust as the authors considered many factors that might affect mortality risk, such as sex, age, and comorbidities, and the results are based on information from a very large number of people – 1.6 million.
However, there’s a major issue with the concept of “skeletal age” as proposed by Dr. Tran and colleagues. The term is already in use and defines the maturity of bones in children and adolescents, also called “bone age” (Greulich and Pyle 1959; Skeletal Age, Radiology Key). This is a real oversight and could cause confusion in interpreting “skeletal age.”
Skeletal age as currently defined in children and adolescents is influenced by chronological age, exposure to certain hormones, nutritional deficiencies, and systemic diseases, and is a predictor of adult height based on the skeletal age and current height. This concept is completely different from that being proposed by the authors in this paper. Dr. Tran and colleagues (and the reviewers of this paper) are probably not familiar with the use of the terminology in youth, which is a major oversight; they should consider changing the terminology given this overlap.
Further, fragility fractures can occur from osteoporosis at any age, and this study doesn’t provide information regarding years of life lost from occurrence of fragility fractures at younger ages, or the age at which mortality risk starts to increase (as the study was performed only in those aged 50 or older).
While the study takes into account general comorbidities in developing the model to define years of life lost, it doesn’t account for other factors that can influence fracture risk, such as lifestyle factors, activity level, and genetic risk (family history of osteoporosis, for example). Of note, the impact of additional fractures isn’t considered either and should be factored into future investigations.
Overall, the study is robust and important and provides valuable information regarding mortality risk from a fragility fracture in older people. However, there are some flaws that need to be considered and addressed, the most serious of which is that the term “skeletal age” has been in existence for decades, applied to a much younger age group, and its implications are completely different from those being proposed by the authors here.
A version of this article first appeared on Medscape.com.
DDW 2023: Common GI conditions in primary care
This transcript has been edited for clarity.
Hello and welcome. I am Vivek Kaul, MD, from the University of Rochester (N.Y.) Medical Center. It gives me great pleasure, once again, to collaborate with WebMD and Medscape to present this video capsule.
This time, we have picked the best GI and GI surgery papers from the recently concluded Digestive Disease Week 2023 international meeting in Chicago. For this edition of the Medscape GI/Primary Care video capsule, I thought it would be nice to present a couple of GI surgical papers that have major impact on common GI conditions seen in primary care.
This first paper in the GI surgery realm is “Diabetes Mellitus Remission in Patients with BMI > 50 kg/m2 after Bariatric Surgeries: A Real-World Multi-Centered Study.” This comes to us from the Mayo Clinic in Rochester, Minn.
This was a retrospective study of 329 patients who had type 2 diabetes, who underwent either Roux-en-Y gastric bypass (two-thirds of them) or a surgical sleeve gastrectomy (about one third of them). The mean follow-up was about 6 years. Type 2 diabetes remission was seen in about half of them in this long-term follow-up.
There were significant improvements in hemoglobin A1c, fasting blood glucose, diabetes, and, of course, weight loss – and all were statistically significant. The type of surgery did not seem to make any difference. Both groups really benefited from this.
The take-home point of this study is that patients who have a high BMI and metabolic syndrome, whether they undergo Roux-en-Y gastric bypass or sleeve gastrectomy, should expect to see long-term, durable, positive impact on their diabetes, as well as weight loss, of course, and all the metrics for blood glucose and hemodynamics.
This is an important study and helps us in counseling patients appropriately when they present for selection for these types of surgeries in the appropriate clinical context.
The next paper in the surgical realm is from the University of Padova (Italy), which is “Antireflux Surgery’s Lifespan: 20 Years After Laparoscopic Fundoplication.” This is a prospective study of 137 patients who underwent laparoscopic fundoplication for the management of gastroesophageal reflux disease (n = 107) or a large hiatal hernia (n = 30).
The median follow-up in this study was 22 years, which is among the longest I’ve seen in recent years for any study. A very small percentage of patients underwent revision surgery, which speaks to the skill set and careful selection of the patient cohort.
Only nine patients of 137 had repeat surgeries. Positive outcomes, on the other hand, were seen in the vast majority of patients with reflux, at 84%, and still, two thirds of patients with hiatal hernia had positive outcomes over the long term.
Failure-free survival was much higher for the gastroesophageal reflux cohort, as expected, compared with the hiatal hernia cohort. Patient satisfaction after two decades was almost 90% both for reflux and for hiatal hernia, which is quite a significant milestone.
The take-home point from this study is that laparoscopic fundoplication is quite durable, with success rates approaching 90%, even 2 decades after the surgical intervention. This is quite an important data point for us to discuss with patients when they present with a question around surgery for these indications. Although, as we know well in the era of PPI therapy, surgical indications are definitely reduced, compared with 20 years ago.
The next paper in this group is related to another very important clinical entity, which is acute pancreatitis and the question of pancreatic cancer in those patients who present with acute pancreatitis.
Our previous work in this realm, published a couple of years ago, suggested that about 3% of patients who come to the hospital with acute pancreatitis may harbor pancreatic malignancy, which can be picked up if we do a diligent follow-up with cross-sectional imaging and endoscopic ultrasound.
This paper talks about acute pancreatitis and the modeling of risk in terms of prediction for early cancer. This study was conducted at the University of Pennsylvania and basically speaks to a clinical prediction model to assess the risk for pancreatic cancer after acute pancreatitis diagnosis.
As we know, the risk for pancreatic cancer is highest within 2 years of the initial presentation of acute pancreatitis, especially if the etiology of that pancreatitis was unclear. In this clinical prediction model, as shown on this slide, a variety of demographic and clinical criteria were used, all of which are easily accessible to us in GI and in primary care to calculate the modeling risk.
A large number of patients were used to apply this model: 51,613 patients. The mean age was 62%, the overwhelming majority were male, and half were Caucasian. Using this clinical prediction model, a 2-year incidence of pancreatic ductal adenocarcinoma was calculated to be 1.6% for an absolute number of 800 cases.
Nearly 50% were discovered after 3 months. There was a positive association with pancreatic cystic disease in these patients, which makes sense in terms of their preneoplastic potential.
The take-home point from this study is that readily available demographic and clinical criteria may be useful in helping us predict diagnosis of early pancreatic cancer in a subset of patients who present with acute pancreatitis, and in my opinion, particularly those who present with pancreatitis for which we cannot explain the etiology.
The next paper we have refers to a very common problem, which is Helicobacter pylori infection. This is almost an endemic problem in the Far East and in the third world, but also an increasing problem in the United States.
This particular study comes to us from Taiwan and is looking at different treatment strategies for H. pylori infection. In Taiwan and the Far East, it has been proposed that high acid content in the food might be interfering with efficacy rates. The consideration for antibiotic resistance may be an issue as well. That’s in the background of this paper.
This paper is titled “Enhanced Efficacy of Combined Bismuth and High-Dose Dual Therapy versus High-Dose Dual Therapy Alone or Quadruple Therapy for First-Line H pylori Eradication.” This was an interim report from a large multicenter, randomized controlled trial and included 436 patients with H. pylori infection.
Each patient had biopsies with H. pylori cultures, and they were randomized to one of three regimens as listed here. They received high-dose dual therapy or bismuth along with high-dose dual therapy – so, triple therapy – or they received the amoxicillin-based bismuth and quadruple-therapy regimen. Breath tests were used to check for eradication at the end of the treatment period.
In terms of the results from this study, it’s very clear that the bismuth-based regimen, which is listed here in the middle column, had the highest treatment efficacy rates and moderate adverse event rates when compared with the other two arms.
Reduced eradication in the dual-therapy arm was seen probably due to increased acid food intake. Reduced eradication in the quadruple-therapy arm was likely associated with antibiotic resistance and also with poor compliance, which is understandable when you have more medications to take compared with the group that has fewer medications to take.
The take-home point from this study was that the addition of bismuth might be the silver bullet when you add that to the dual-therapy regimen in difficult cases of H pylori infection. More to come on this, and certainly of relevance to us here as we tackle more and more cases of H. pylori infection stateside.
Last but not least, GI and primary care discussions can never be complete without a discussion on colorectal cancer screening. As the NordICC trial has shown us, it’s not the issue with the screening modality but more about patients’ acceptance of screening, particularly invasive screening.
This paper looked at different strategies and tried to figure out which strategy would be most attractive to bring more people in for screening. This is a large, randomized controlled trial with good distribution of patient populations with approximately half female, half White, and a mean age around 48 years, with more than 20,000 patients.
One of four screening strategies was used. Patients were invited for a fecal immunochemical test, a colonoscopy, or they were invited to choose between a FIT test and a colonoscopy. The final group was mailed a FIT test kit as an outreach mechanism.
Invitations were sent via electronic patient portals, which are very common nowadays, and via the United States Postal Service. Text-message reminders were sent a couple of weeks later. The primary outcome of this study was to look at any colorectal cancer completion rate at 26 weeks.
The results of the study were quite interesting. Screening completion rates were relatively low at 18%. It was interesting to note that the highest screening rates were seen with those who had the FIT test mailed to them, whereas each of the other three groups that had only invitations sent to them had relatively lower screening compliance rates.
The lowest participation was in the colonoscopy invitation group, I suspect due to the invasive nature of the procedure and the patients’ perception of that. When patients were offered a choice, they were more likely to be compliant with screening. In the end, more patients chose colonoscopy as their screening test of choice compared with FIT testing.
The take-home point from this study is that directly sending test kits as an outreach might be more effective than simply inviting subjects to be screened. From those who do respond to be screened, more patients would choose colonoscopy, compared with the FIT test.
With that, I come to the end of this video capsule summary for the Best of GI for Primary Care from DDW 2023. We covered a variety of topics, ranging from pancreatitis to H pylori to colon cancer screening and a couple of GI surgical interventions with long-term outcomes that are very favorable.
Dr. Kaul disclosed conflicts of interest with AMBU, Cook Medical, CDS, CDX,Steris, and Motus GI.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Hello and welcome. I am Vivek Kaul, MD, from the University of Rochester (N.Y.) Medical Center. It gives me great pleasure, once again, to collaborate with WebMD and Medscape to present this video capsule.
This time, we have picked the best GI and GI surgery papers from the recently concluded Digestive Disease Week 2023 international meeting in Chicago. For this edition of the Medscape GI/Primary Care video capsule, I thought it would be nice to present a couple of GI surgical papers that have major impact on common GI conditions seen in primary care.
This first paper in the GI surgery realm is “Diabetes Mellitus Remission in Patients with BMI > 50 kg/m2 after Bariatric Surgeries: A Real-World Multi-Centered Study.” This comes to us from the Mayo Clinic in Rochester, Minn.
This was a retrospective study of 329 patients who had type 2 diabetes, who underwent either Roux-en-Y gastric bypass (two-thirds of them) or a surgical sleeve gastrectomy (about one third of them). The mean follow-up was about 6 years. Type 2 diabetes remission was seen in about half of them in this long-term follow-up.
There were significant improvements in hemoglobin A1c, fasting blood glucose, diabetes, and, of course, weight loss – and all were statistically significant. The type of surgery did not seem to make any difference. Both groups really benefited from this.
The take-home point of this study is that patients who have a high BMI and metabolic syndrome, whether they undergo Roux-en-Y gastric bypass or sleeve gastrectomy, should expect to see long-term, durable, positive impact on their diabetes, as well as weight loss, of course, and all the metrics for blood glucose and hemodynamics.
This is an important study and helps us in counseling patients appropriately when they present for selection for these types of surgeries in the appropriate clinical context.
The next paper in the surgical realm is from the University of Padova (Italy), which is “Antireflux Surgery’s Lifespan: 20 Years After Laparoscopic Fundoplication.” This is a prospective study of 137 patients who underwent laparoscopic fundoplication for the management of gastroesophageal reflux disease (n = 107) or a large hiatal hernia (n = 30).
The median follow-up in this study was 22 years, which is among the longest I’ve seen in recent years for any study. A very small percentage of patients underwent revision surgery, which speaks to the skill set and careful selection of the patient cohort.
Only nine patients of 137 had repeat surgeries. Positive outcomes, on the other hand, were seen in the vast majority of patients with reflux, at 84%, and still, two thirds of patients with hiatal hernia had positive outcomes over the long term.
Failure-free survival was much higher for the gastroesophageal reflux cohort, as expected, compared with the hiatal hernia cohort. Patient satisfaction after two decades was almost 90% both for reflux and for hiatal hernia, which is quite a significant milestone.
The take-home point from this study is that laparoscopic fundoplication is quite durable, with success rates approaching 90%, even 2 decades after the surgical intervention. This is quite an important data point for us to discuss with patients when they present with a question around surgery for these indications. Although, as we know well in the era of PPI therapy, surgical indications are definitely reduced, compared with 20 years ago.
The next paper in this group is related to another very important clinical entity, which is acute pancreatitis and the question of pancreatic cancer in those patients who present with acute pancreatitis.
Our previous work in this realm, published a couple of years ago, suggested that about 3% of patients who come to the hospital with acute pancreatitis may harbor pancreatic malignancy, which can be picked up if we do a diligent follow-up with cross-sectional imaging and endoscopic ultrasound.
This paper talks about acute pancreatitis and the modeling of risk in terms of prediction for early cancer. This study was conducted at the University of Pennsylvania and basically speaks to a clinical prediction model to assess the risk for pancreatic cancer after acute pancreatitis diagnosis.
As we know, the risk for pancreatic cancer is highest within 2 years of the initial presentation of acute pancreatitis, especially if the etiology of that pancreatitis was unclear. In this clinical prediction model, as shown on this slide, a variety of demographic and clinical criteria were used, all of which are easily accessible to us in GI and in primary care to calculate the modeling risk.
A large number of patients were used to apply this model: 51,613 patients. The mean age was 62%, the overwhelming majority were male, and half were Caucasian. Using this clinical prediction model, a 2-year incidence of pancreatic ductal adenocarcinoma was calculated to be 1.6% for an absolute number of 800 cases.
Nearly 50% were discovered after 3 months. There was a positive association with pancreatic cystic disease in these patients, which makes sense in terms of their preneoplastic potential.
The take-home point from this study is that readily available demographic and clinical criteria may be useful in helping us predict diagnosis of early pancreatic cancer in a subset of patients who present with acute pancreatitis, and in my opinion, particularly those who present with pancreatitis for which we cannot explain the etiology.
The next paper we have refers to a very common problem, which is Helicobacter pylori infection. This is almost an endemic problem in the Far East and in the third world, but also an increasing problem in the United States.
This particular study comes to us from Taiwan and is looking at different treatment strategies for H. pylori infection. In Taiwan and the Far East, it has been proposed that high acid content in the food might be interfering with efficacy rates. The consideration for antibiotic resistance may be an issue as well. That’s in the background of this paper.
This paper is titled “Enhanced Efficacy of Combined Bismuth and High-Dose Dual Therapy versus High-Dose Dual Therapy Alone or Quadruple Therapy for First-Line H pylori Eradication.” This was an interim report from a large multicenter, randomized controlled trial and included 436 patients with H. pylori infection.
Each patient had biopsies with H. pylori cultures, and they were randomized to one of three regimens as listed here. They received high-dose dual therapy or bismuth along with high-dose dual therapy – so, triple therapy – or they received the amoxicillin-based bismuth and quadruple-therapy regimen. Breath tests were used to check for eradication at the end of the treatment period.
In terms of the results from this study, it’s very clear that the bismuth-based regimen, which is listed here in the middle column, had the highest treatment efficacy rates and moderate adverse event rates when compared with the other two arms.
Reduced eradication in the dual-therapy arm was seen probably due to increased acid food intake. Reduced eradication in the quadruple-therapy arm was likely associated with antibiotic resistance and also with poor compliance, which is understandable when you have more medications to take compared with the group that has fewer medications to take.
The take-home point from this study was that the addition of bismuth might be the silver bullet when you add that to the dual-therapy regimen in difficult cases of H pylori infection. More to come on this, and certainly of relevance to us here as we tackle more and more cases of H. pylori infection stateside.
Last but not least, GI and primary care discussions can never be complete without a discussion on colorectal cancer screening. As the NordICC trial has shown us, it’s not the issue with the screening modality but more about patients’ acceptance of screening, particularly invasive screening.
This paper looked at different strategies and tried to figure out which strategy would be most attractive to bring more people in for screening. This is a large, randomized controlled trial with good distribution of patient populations with approximately half female, half White, and a mean age around 48 years, with more than 20,000 patients.
One of four screening strategies was used. Patients were invited for a fecal immunochemical test, a colonoscopy, or they were invited to choose between a FIT test and a colonoscopy. The final group was mailed a FIT test kit as an outreach mechanism.
Invitations were sent via electronic patient portals, which are very common nowadays, and via the United States Postal Service. Text-message reminders were sent a couple of weeks later. The primary outcome of this study was to look at any colorectal cancer completion rate at 26 weeks.
The results of the study were quite interesting. Screening completion rates were relatively low at 18%. It was interesting to note that the highest screening rates were seen with those who had the FIT test mailed to them, whereas each of the other three groups that had only invitations sent to them had relatively lower screening compliance rates.
The lowest participation was in the colonoscopy invitation group, I suspect due to the invasive nature of the procedure and the patients’ perception of that. When patients were offered a choice, they were more likely to be compliant with screening. In the end, more patients chose colonoscopy as their screening test of choice compared with FIT testing.
The take-home point from this study is that directly sending test kits as an outreach might be more effective than simply inviting subjects to be screened. From those who do respond to be screened, more patients would choose colonoscopy, compared with the FIT test.
With that, I come to the end of this video capsule summary for the Best of GI for Primary Care from DDW 2023. We covered a variety of topics, ranging from pancreatitis to H pylori to colon cancer screening and a couple of GI surgical interventions with long-term outcomes that are very favorable.
Dr. Kaul disclosed conflicts of interest with AMBU, Cook Medical, CDS, CDX,Steris, and Motus GI.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Hello and welcome. I am Vivek Kaul, MD, from the University of Rochester (N.Y.) Medical Center. It gives me great pleasure, once again, to collaborate with WebMD and Medscape to present this video capsule.
This time, we have picked the best GI and GI surgery papers from the recently concluded Digestive Disease Week 2023 international meeting in Chicago. For this edition of the Medscape GI/Primary Care video capsule, I thought it would be nice to present a couple of GI surgical papers that have major impact on common GI conditions seen in primary care.
This first paper in the GI surgery realm is “Diabetes Mellitus Remission in Patients with BMI > 50 kg/m2 after Bariatric Surgeries: A Real-World Multi-Centered Study.” This comes to us from the Mayo Clinic in Rochester, Minn.
This was a retrospective study of 329 patients who had type 2 diabetes, who underwent either Roux-en-Y gastric bypass (two-thirds of them) or a surgical sleeve gastrectomy (about one third of them). The mean follow-up was about 6 years. Type 2 diabetes remission was seen in about half of them in this long-term follow-up.
There were significant improvements in hemoglobin A1c, fasting blood glucose, diabetes, and, of course, weight loss – and all were statistically significant. The type of surgery did not seem to make any difference. Both groups really benefited from this.
The take-home point of this study is that patients who have a high BMI and metabolic syndrome, whether they undergo Roux-en-Y gastric bypass or sleeve gastrectomy, should expect to see long-term, durable, positive impact on their diabetes, as well as weight loss, of course, and all the metrics for blood glucose and hemodynamics.
This is an important study and helps us in counseling patients appropriately when they present for selection for these types of surgeries in the appropriate clinical context.
The next paper in the surgical realm is from the University of Padova (Italy), which is “Antireflux Surgery’s Lifespan: 20 Years After Laparoscopic Fundoplication.” This is a prospective study of 137 patients who underwent laparoscopic fundoplication for the management of gastroesophageal reflux disease (n = 107) or a large hiatal hernia (n = 30).
The median follow-up in this study was 22 years, which is among the longest I’ve seen in recent years for any study. A very small percentage of patients underwent revision surgery, which speaks to the skill set and careful selection of the patient cohort.
Only nine patients of 137 had repeat surgeries. Positive outcomes, on the other hand, were seen in the vast majority of patients with reflux, at 84%, and still, two thirds of patients with hiatal hernia had positive outcomes over the long term.
Failure-free survival was much higher for the gastroesophageal reflux cohort, as expected, compared with the hiatal hernia cohort. Patient satisfaction after two decades was almost 90% both for reflux and for hiatal hernia, which is quite a significant milestone.
The take-home point from this study is that laparoscopic fundoplication is quite durable, with success rates approaching 90%, even 2 decades after the surgical intervention. This is quite an important data point for us to discuss with patients when they present with a question around surgery for these indications. Although, as we know well in the era of PPI therapy, surgical indications are definitely reduced, compared with 20 years ago.
The next paper in this group is related to another very important clinical entity, which is acute pancreatitis and the question of pancreatic cancer in those patients who present with acute pancreatitis.
Our previous work in this realm, published a couple of years ago, suggested that about 3% of patients who come to the hospital with acute pancreatitis may harbor pancreatic malignancy, which can be picked up if we do a diligent follow-up with cross-sectional imaging and endoscopic ultrasound.
This paper talks about acute pancreatitis and the modeling of risk in terms of prediction for early cancer. This study was conducted at the University of Pennsylvania and basically speaks to a clinical prediction model to assess the risk for pancreatic cancer after acute pancreatitis diagnosis.
As we know, the risk for pancreatic cancer is highest within 2 years of the initial presentation of acute pancreatitis, especially if the etiology of that pancreatitis was unclear. In this clinical prediction model, as shown on this slide, a variety of demographic and clinical criteria were used, all of which are easily accessible to us in GI and in primary care to calculate the modeling risk.
A large number of patients were used to apply this model: 51,613 patients. The mean age was 62%, the overwhelming majority were male, and half were Caucasian. Using this clinical prediction model, a 2-year incidence of pancreatic ductal adenocarcinoma was calculated to be 1.6% for an absolute number of 800 cases.
Nearly 50% were discovered after 3 months. There was a positive association with pancreatic cystic disease in these patients, which makes sense in terms of their preneoplastic potential.
The take-home point from this study is that readily available demographic and clinical criteria may be useful in helping us predict diagnosis of early pancreatic cancer in a subset of patients who present with acute pancreatitis, and in my opinion, particularly those who present with pancreatitis for which we cannot explain the etiology.
The next paper we have refers to a very common problem, which is Helicobacter pylori infection. This is almost an endemic problem in the Far East and in the third world, but also an increasing problem in the United States.
This particular study comes to us from Taiwan and is looking at different treatment strategies for H. pylori infection. In Taiwan and the Far East, it has been proposed that high acid content in the food might be interfering with efficacy rates. The consideration for antibiotic resistance may be an issue as well. That’s in the background of this paper.
This paper is titled “Enhanced Efficacy of Combined Bismuth and High-Dose Dual Therapy versus High-Dose Dual Therapy Alone or Quadruple Therapy for First-Line H pylori Eradication.” This was an interim report from a large multicenter, randomized controlled trial and included 436 patients with H. pylori infection.
Each patient had biopsies with H. pylori cultures, and they were randomized to one of three regimens as listed here. They received high-dose dual therapy or bismuth along with high-dose dual therapy – so, triple therapy – or they received the amoxicillin-based bismuth and quadruple-therapy regimen. Breath tests were used to check for eradication at the end of the treatment period.
In terms of the results from this study, it’s very clear that the bismuth-based regimen, which is listed here in the middle column, had the highest treatment efficacy rates and moderate adverse event rates when compared with the other two arms.
Reduced eradication in the dual-therapy arm was seen probably due to increased acid food intake. Reduced eradication in the quadruple-therapy arm was likely associated with antibiotic resistance and also with poor compliance, which is understandable when you have more medications to take compared with the group that has fewer medications to take.
The take-home point from this study was that the addition of bismuth might be the silver bullet when you add that to the dual-therapy regimen in difficult cases of H pylori infection. More to come on this, and certainly of relevance to us here as we tackle more and more cases of H. pylori infection stateside.
Last but not least, GI and primary care discussions can never be complete without a discussion on colorectal cancer screening. As the NordICC trial has shown us, it’s not the issue with the screening modality but more about patients’ acceptance of screening, particularly invasive screening.
This paper looked at different strategies and tried to figure out which strategy would be most attractive to bring more people in for screening. This is a large, randomized controlled trial with good distribution of patient populations with approximately half female, half White, and a mean age around 48 years, with more than 20,000 patients.
One of four screening strategies was used. Patients were invited for a fecal immunochemical test, a colonoscopy, or they were invited to choose between a FIT test and a colonoscopy. The final group was mailed a FIT test kit as an outreach mechanism.
Invitations were sent via electronic patient portals, which are very common nowadays, and via the United States Postal Service. Text-message reminders were sent a couple of weeks later. The primary outcome of this study was to look at any colorectal cancer completion rate at 26 weeks.
The results of the study were quite interesting. Screening completion rates were relatively low at 18%. It was interesting to note that the highest screening rates were seen with those who had the FIT test mailed to them, whereas each of the other three groups that had only invitations sent to them had relatively lower screening compliance rates.
The lowest participation was in the colonoscopy invitation group, I suspect due to the invasive nature of the procedure and the patients’ perception of that. When patients were offered a choice, they were more likely to be compliant with screening. In the end, more patients chose colonoscopy as their screening test of choice compared with FIT testing.
The take-home point from this study is that directly sending test kits as an outreach might be more effective than simply inviting subjects to be screened. From those who do respond to be screened, more patients would choose colonoscopy, compared with the FIT test.
With that, I come to the end of this video capsule summary for the Best of GI for Primary Care from DDW 2023. We covered a variety of topics, ranging from pancreatitis to H pylori to colon cancer screening and a couple of GI surgical interventions with long-term outcomes that are very favorable.
Dr. Kaul disclosed conflicts of interest with AMBU, Cook Medical, CDS, CDX,Steris, and Motus GI.
A version of this article first appeared on Medscape.com.