Photo by Rhoda Baer

MADRID—Patients with advanced Hodgkin lymphoma (HL) who are PET-negative after initial treatment with 2 cycles of eBEACOPP* should only receive 2 additional cycles of the therapy, new research suggests.

In the HD18 trial, PET-2-negative patients who received 4 cycles of eBEACOPP had non-inferior progression-free survival (PFS) and significantly better overall survival (OS) than PET-2-negative patients who received 6 or 8 cycles of the treatment.

Patients who received 4 cycles also had less severe toxicity and fewer second neoplasms than patients who received more cycles of eBEACOPP.

“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far,” said Peter Borchmann, MD, of University Hospital of Cologne in Germany.

“That’s why we recommend treatment with PET-2-guided eBEACOPP for patients with newly diagnosed, advanced-stage Hodgkin lymphoma.”

Dr Borchmann presented results from HD18 at the 22nd Congress of the European Hematology Association (EHA) as abstract S150.

Patients and treatment

Dr Borchmann and his colleagues set out to determine if they could decrease the number of eBEACOPP cycles in patients with negative PET-2 without compromising treatment efficacy.

From May 2008 to July 2014, the researchers recruited 2101 patients with newly diagnosed, advanced-stage HL.

Patients who were PET-negative after 2 cycles of eBEACOPP (n=1005) were initially randomized to receive 6 additional cycles of eBEACOPP or 2 additional cycles—a total of 8 cycles or 4 cycles, respectively. The protocol was later amended (in June 2011), and the total number of cycles in the standard therapy arm was reduced to 6.

There were 504 patients in the standard therapy arm—288 who received 8 cycles of eBEACOPP and 216 who received 6 cycles. There were 501 patients who received 4 cycles of eBEACOPP.

Sixteen patients in the standard therapy arm and 17 in the 4-cycle arm also received radiotherapy.

The median age was 32 (range, 18-60) in the standard therapy arm and 33 (range, 18-60) in the 4-cycle arm. Sixty-three percent and 62% of patients, respectively, were male.

Eight percent of patients in both arms had Ann Arbor stage IIB disease. Fifty-seven percent in the standard therapy arm and 55% in the 4-cycle arm had stage IIIA/B. And 35% and 36%, respectively, had stage IVA/B disease.

Thirty-five percent of patients in both arms had an IPS stage of 0-1. Fifty-one percent in the standard therapy arm and 52% in the 4-cycle arm had an IPS stage of 2-3. And 14% in both arms had an IPS stage of 4-7.

The median duration of therapy was 173 days (range, 41-266) for patients randomized to receive 8 cycles of eBEACOPP, 129 days (range, 35-178) in patients randomized to receive 6 cycles, and 85 days (range, 42-133) in patients randomized to receive 4 cycles.

One patient in the 6-cycle group received more than 6 cycles, and 6 patients in the 4-cycle arm received more than 4 cycles.

PFS and OS

The median follow-up was 55 months. The estimated 3-year PFS was 92.3% in the standard therapy arm and 94.8% in the 4-cycle arm. The estimated 5-year PFS was 91.2% and 91.8%, respectively. The hazard ratio was 0.88.

“[Based on these data,] we can conclude that 4 cycles are as effective as 6 or 8 cycles,” Dr Borchmann said.

The estimated 3-year OS was 95.9% in the standard therapy arm and 98.7% in the 4-cycle arm. The estimated 5-year OS was 95.4% and 97.6%, respectively. The hazard ratio was 0.36 (P=0.006).

Toxicity and second neoplasms

Grade 3/4 organ toxicity occurred in 22% of patients in the 8-cycle group, 13% in the 6-cycle group, and 8% in the 4-cycle group. Grade 4 anemia, thrombocytopenia, or infection occurred in 59%, 53%, and 38%, respectively.

Treatment-related morbidity occurred in 66% of patients in the 8-cycle group, 61% in the 6-cycle group, and 41% in the 4-cycle group.

Eighteen patients in the standard therapy arm had second neoplasms—8 with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), 5 with non-Hodgkin lymphoma (NHL), and 5 with solid tumors.

Thirteen patients in the 4-cycle arm had second neoplasms—2 with AML/MDS, 8 with NHL, and 3 with solid tumors.

Causes of death

The cause of death was HL for 0.6% of patients (n=3) in the standard therapy arm and for 0.8% of patients (n=4) in the 4-cycle arm.

The cause of death was second malignancy for 2.2% of patients (n=11) in the standard therapy arm. Five patients died of AML, 3 of NHL, and 3 of solid tumor malignancies.

One patient (0.2%) in the 4-cycle arm died as a result of a second malignancy, which was AML.

Toxicity related to study treatment was the cause of death for 1.2% (n=6) of patients in the standard therapy arm. Five of the patients died of infection, and the sixth died of ischemic stroke.

None of the patients in the 4-cycle arm died of toxicity related to study treatment.

Other causes of death included toxicity of salvage treatment (0.4%, n=2 in both arms), other disease (0.2%, n=1 in both arms), accident (1 patient [0.2%] in the 4-cycle arm), and unknown cause (2 patients [0.4%] in the standard arm).

“[With 4 cycles of therapy,] we had a significant and very relevant reduction of severe, acute hematological and non-hematological toxicities, and this was accompanied by a relevant reduction of mortality for other reasons than HL,” Dr Borchmann said. “And we’ve almost eliminated HL as a cause of death in this trial.” 

*dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone

Photo by Rhoda Baer

MADRID—Patients with advanced Hodgkin lymphoma (HL) who are PET-negative after initial treatment with 2 cycles of eBEACOPP* should only receive 2 additional cycles of the therapy, new research suggests.

In the HD18 trial, PET-2-negative patients who received 4 cycles of eBEACOPP had non-inferior progression-free survival (PFS) and significantly better overall survival (OS) than PET-2-negative patients who received 6 or 8 cycles of the treatment.

Patients who received 4 cycles also had less severe toxicity and fewer second neoplasms than patients who received more cycles of eBEACOPP.

“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far,” said Peter Borchmann, MD, of University Hospital of Cologne in Germany.

“That’s why we recommend treatment with PET-2-guided eBEACOPP for patients with newly diagnosed, advanced-stage Hodgkin lymphoma.”

Dr Borchmann presented results from HD18 at the 22nd Congress of the European Hematology Association (EHA) as abstract S150.

Patients and treatment

Dr Borchmann and his colleagues set out to determine if they could decrease the number of eBEACOPP cycles in patients with negative PET-2 without compromising treatment efficacy.

From May 2008 to July 2014, the researchers recruited 2101 patients with newly diagnosed, advanced-stage HL.

Patients who were PET-negative after 2 cycles of eBEACOPP (n=1005) were initially randomized to receive 6 additional cycles of eBEACOPP or 2 additional cycles—a total of 8 cycles or 4 cycles, respectively. The protocol was later amended (in June 2011), and the total number of cycles in the standard therapy arm was reduced to 6.

There were 504 patients in the standard therapy arm—288 who received 8 cycles of eBEACOPP and 216 who received 6 cycles. There were 501 patients who received 4 cycles of eBEACOPP.

Sixteen patients in the standard therapy arm and 17 in the 4-cycle arm also received radiotherapy.

The median age was 32 (range, 18-60) in the standard therapy arm and 33 (range, 18-60) in the 4-cycle arm. Sixty-three percent and 62% of patients, respectively, were male.

Eight percent of patients in both arms had Ann Arbor stage IIB disease. Fifty-seven percent in the standard therapy arm and 55% in the 4-cycle arm had stage IIIA/B. And 35% and 36%, respectively, had stage IVA/B disease.

Thirty-five percent of patients in both arms had an IPS stage of 0-1. Fifty-one percent in the standard therapy arm and 52% in the 4-cycle arm had an IPS stage of 2-3. And 14% in both arms had an IPS stage of 4-7.

The median duration of therapy was 173 days (range, 41-266) for patients randomized to receive 8 cycles of eBEACOPP, 129 days (range, 35-178) in patients randomized to receive 6 cycles, and 85 days (range, 42-133) in patients randomized to receive 4 cycles.

One patient in the 6-cycle group received more than 6 cycles, and 6 patients in the 4-cycle arm received more than 4 cycles.

PFS and OS

The median follow-up was 55 months. The estimated 3-year PFS was 92.3% in the standard therapy arm and 94.8% in the 4-cycle arm. The estimated 5-year PFS was 91.2% and 91.8%, respectively. The hazard ratio was 0.88.

“[Based on these data,] we can conclude that 4 cycles are as effective as 6 or 8 cycles,” Dr Borchmann said.

The estimated 3-year OS was 95.9% in the standard therapy arm and 98.7% in the 4-cycle arm. The estimated 5-year OS was 95.4% and 97.6%, respectively. The hazard ratio was 0.36 (P=0.006).

Toxicity and second neoplasms

Grade 3/4 organ toxicity occurred in 22% of patients in the 8-cycle group, 13% in the 6-cycle group, and 8% in the 4-cycle group. Grade 4 anemia, thrombocytopenia, or infection occurred in 59%, 53%, and 38%, respectively.

Treatment-related morbidity occurred in 66% of patients in the 8-cycle group, 61% in the 6-cycle group, and 41% in the 4-cycle group.

Eighteen patients in the standard therapy arm had second neoplasms—8 with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), 5 with non-Hodgkin lymphoma (NHL), and 5 with solid tumors.

Thirteen patients in the 4-cycle arm had second neoplasms—2 with AML/MDS, 8 with NHL, and 3 with solid tumors.

Causes of death

The cause of death was HL for 0.6% of patients (n=3) in the standard therapy arm and for 0.8% of patients (n=4) in the 4-cycle arm.

The cause of death was second malignancy for 2.2% of patients (n=11) in the standard therapy arm. Five patients died of AML, 3 of NHL, and 3 of solid tumor malignancies.

One patient (0.2%) in the 4-cycle arm died as a result of a second malignancy, which was AML.

Toxicity related to study treatment was the cause of death for 1.2% (n=6) of patients in the standard therapy arm. Five of the patients died of infection, and the sixth died of ischemic stroke.

None of the patients in the 4-cycle arm died of toxicity related to study treatment.

Other causes of death included toxicity of salvage treatment (0.4%, n=2 in both arms), other disease (0.2%, n=1 in both arms), accident (1 patient [0.2%] in the 4-cycle arm), and unknown cause (2 patients [0.4%] in the standard arm).

“[With 4 cycles of therapy,] we had a significant and very relevant reduction of severe, acute hematological and non-hematological toxicities, and this was accompanied by a relevant reduction of mortality for other reasons than HL,” Dr Borchmann said. “And we’ve almost eliminated HL as a cause of death in this trial.” 

*dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone

Photo by Rhoda Baer

MADRID—Patients with advanced Hodgkin lymphoma (HL) who are PET-negative after initial treatment with 2 cycles of eBEACOPP* should only receive 2 additional cycles of the therapy, new research suggests.

In the HD18 trial, PET-2-negative patients who received 4 cycles of eBEACOPP had non-inferior progression-free survival (PFS) and significantly better overall survival (OS) than PET-2-negative patients who received 6 or 8 cycles of the treatment.

Patients who received 4 cycles also had less severe toxicity and fewer second neoplasms than patients who received more cycles of eBEACOPP.

“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far,” said Peter Borchmann, MD, of University Hospital of Cologne in Germany.

“That’s why we recommend treatment with PET-2-guided eBEACOPP for patients with newly diagnosed, advanced-stage Hodgkin lymphoma.”

Dr Borchmann presented results from HD18 at the 22nd Congress of the European Hematology Association (EHA) as abstract S150.

Patients and treatment

Dr Borchmann and his colleagues set out to determine if they could decrease the number of eBEACOPP cycles in patients with negative PET-2 without compromising treatment efficacy.

From May 2008 to July 2014, the researchers recruited 2101 patients with newly diagnosed, advanced-stage HL.

Patients who were PET-negative after 2 cycles of eBEACOPP (n=1005) were initially randomized to receive 6 additional cycles of eBEACOPP or 2 additional cycles—a total of 8 cycles or 4 cycles, respectively. The protocol was later amended (in June 2011), and the total number of cycles in the standard therapy arm was reduced to 6.

There were 504 patients in the standard therapy arm—288 who received 8 cycles of eBEACOPP and 216 who received 6 cycles. There were 501 patients who received 4 cycles of eBEACOPP.

Sixteen patients in the standard therapy arm and 17 in the 4-cycle arm also received radiotherapy.

The median age was 32 (range, 18-60) in the standard therapy arm and 33 (range, 18-60) in the 4-cycle arm. Sixty-three percent and 62% of patients, respectively, were male.

Eight percent of patients in both arms had Ann Arbor stage IIB disease. Fifty-seven percent in the standard therapy arm and 55% in the 4-cycle arm had stage IIIA/B. And 35% and 36%, respectively, had stage IVA/B disease.

Thirty-five percent of patients in both arms had an IPS stage of 0-1. Fifty-one percent in the standard therapy arm and 52% in the 4-cycle arm had an IPS stage of 2-3. And 14% in both arms had an IPS stage of 4-7.

The median duration of therapy was 173 days (range, 41-266) for patients randomized to receive 8 cycles of eBEACOPP, 129 days (range, 35-178) in patients randomized to receive 6 cycles, and 85 days (range, 42-133) in patients randomized to receive 4 cycles.

One patient in the 6-cycle group received more than 6 cycles, and 6 patients in the 4-cycle arm received more than 4 cycles.

PFS and OS

The median follow-up was 55 months. The estimated 3-year PFS was 92.3% in the standard therapy arm and 94.8% in the 4-cycle arm. The estimated 5-year PFS was 91.2% and 91.8%, respectively. The hazard ratio was 0.88.

“[Based on these data,] we can conclude that 4 cycles are as effective as 6 or 8 cycles,” Dr Borchmann said.

The estimated 3-year OS was 95.9% in the standard therapy arm and 98.7% in the 4-cycle arm. The estimated 5-year OS was 95.4% and 97.6%, respectively. The hazard ratio was 0.36 (P=0.006).

Toxicity and second neoplasms

Grade 3/4 organ toxicity occurred in 22% of patients in the 8-cycle group, 13% in the 6-cycle group, and 8% in the 4-cycle group. Grade 4 anemia, thrombocytopenia, or infection occurred in 59%, 53%, and 38%, respectively.

Treatment-related morbidity occurred in 66% of patients in the 8-cycle group, 61% in the 6-cycle group, and 41% in the 4-cycle group.

Eighteen patients in the standard therapy arm had second neoplasms—8 with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), 5 with non-Hodgkin lymphoma (NHL), and 5 with solid tumors.

Thirteen patients in the 4-cycle arm had second neoplasms—2 with AML/MDS, 8 with NHL, and 3 with solid tumors.

Causes of death

The cause of death was HL for 0.6% of patients (n=3) in the standard therapy arm and for 0.8% of patients (n=4) in the 4-cycle arm.

The cause of death was second malignancy for 2.2% of patients (n=11) in the standard therapy arm. Five patients died of AML, 3 of NHL, and 3 of solid tumor malignancies.

One patient (0.2%) in the 4-cycle arm died as a result of a second malignancy, which was AML.

Toxicity related to study treatment was the cause of death for 1.2% (n=6) of patients in the standard therapy arm. Five of the patients died of infection, and the sixth died of ischemic stroke.

None of the patients in the 4-cycle arm died of toxicity related to study treatment.

Other causes of death included toxicity of salvage treatment (0.4%, n=2 in both arms), other disease (0.2%, n=1 in both arms), accident (1 patient [0.2%] in the 4-cycle arm), and unknown cause (2 patients [0.4%] in the standard arm).

“[With 4 cycles of therapy,] we had a significant and very relevant reduction of severe, acute hematological and non-hematological toxicities, and this was accompanied by a relevant reduction of mortality for other reasons than HL,” Dr Borchmann said. “And we’ve almost eliminated HL as a cause of death in this trial.” 

*dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone

Photo courtesy of Columbia University

A small retrospective study of survivors of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) has found that phosphorylated Tau (p-Tau) in patients’ cerebrospinal fluid (CSF) is a predictor of late neurocognitive consequences.

Investigators compared intellectual performance, memory, and executive functioning between survivors and control subjects and observed that CSF levels of p-Tau during treatment and total intrathecal methotrexate dose negatively correlated with intellectual performance.

They suggest that identifying at-risk children early “could inspire interventions to prevent or remediate chemotherapy-induced cognitive sequelae.”

The investigators enrolled 31 nonirradiated adults, 27 who had had ALL and 4 NHL. They compared the survivors to 35 age-matched controls.

All study participants were a mean age of 21.5 years (range, 16.1–29.8). The mean age of the survivors at diagnosis was 6.4 years.

"Our team collected samples of brain fluid during the cancer treatment,” Rudi D’Hooge, PhD, of KU Leuven in Belgium, said. “We analyzed the p-Tau levels to measure the damage to the brain cells."

Investigators assessed intelligence, memory, and executive function using Wechsler Adult Intelligence Scale (WAIS IV), Rey Auditory Verbal Learning Test (AVLT), and Amsterdam Neuropsychological Tasks (ANT), respectively.

Statistical analysis included two-sided, one-way analysis of covariance (ANCOVA) with survivor group vs control group as an independent factor.  Parental socioeconomic status was a covariate.

Dr D’Hooge and colleagues published their findings in JNCI, the Journal of the National Cancer Institute.

Findings

Investigators found that survivors had statistically significant lower total intelligence (P=0.001), verbal intelligence (P=0.02), and performance intelligence (P=0.007) quotients than controls.

They also found a negative correlation between CSF p-Tau, but not CSF Tau, levels and total intelligence (P=0.02), verbal intelligence (P=0.001), and performance intelligence (P=0.04) quotients.

Only performance intelligence was negatively correlated with total intrathecal methotrexate (P=0.007).

And because total intrathecal methotrexate dose and CSF p-Tau were not significantly correlated (P=0.29), the investigators believe intervening factors increase CSF p-Tau independently from methotrexate dose.

Results of subset tests revealed that cognitive flexibility (set-shifting and working memory), and processing speed were affected (P<0.05).

However, long-term memory, focused and sustained attention, and inhibition appeared unaffected (P>0.05).

The investigators believe these differences in vulnerability of cognitive functions parallel patient age at time of development.

For example, long-term memory, focused and sustained attention, and inhibition develop before children reach 6 years, the mean age at which the survivor cohort was diagnosed.

But set-shifting, working memory, and processing speed mature during adolescence, after the patients were diagnosed and treated.

Limitations of the study, according to the investigators, include its retrospective and cross-sectional design, the relatively small sample size, and the lack of pretreatment neurocognitive data.

Nevertheless, they believe the study should encourage the use of the CSF biomarker, intrathecal methotrexate dose, and age at therapy initiation in neurotoxicity assessments to identify children at risk for long-term sequelae.

"If we systematically measure these p-Tau levels in the future," Iris Elens, MD, also of KU Leuven, said, "we can offer specific help to children with high values. With early coaching aimed at the most relevant functions we can prevent problems that would otherwise manifest 10 to 15 years after the treatment."

The Olivia Hendrickx Research Fund supported the study. 

Photo courtesy of Columbia University

A small retrospective study of survivors of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) has found that phosphorylated Tau (p-Tau) in patients’ cerebrospinal fluid (CSF) is a predictor of late neurocognitive consequences.

Investigators compared intellectual performance, memory, and executive functioning between survivors and control subjects and observed that CSF levels of p-Tau during treatment and total intrathecal methotrexate dose negatively correlated with intellectual performance.

They suggest that identifying at-risk children early “could inspire interventions to prevent or remediate chemotherapy-induced cognitive sequelae.”

The investigators enrolled 31 nonirradiated adults, 27 who had had ALL and 4 NHL. They compared the survivors to 35 age-matched controls.

All study participants were a mean age of 21.5 years (range, 16.1–29.8). The mean age of the survivors at diagnosis was 6.4 years.

"Our team collected samples of brain fluid during the cancer treatment,” Rudi D’Hooge, PhD, of KU Leuven in Belgium, said. “We analyzed the p-Tau levels to measure the damage to the brain cells."

Investigators assessed intelligence, memory, and executive function using Wechsler Adult Intelligence Scale (WAIS IV), Rey Auditory Verbal Learning Test (AVLT), and Amsterdam Neuropsychological Tasks (ANT), respectively.

Statistical analysis included two-sided, one-way analysis of covariance (ANCOVA) with survivor group vs control group as an independent factor.  Parental socioeconomic status was a covariate.

Dr D’Hooge and colleagues published their findings in JNCI, the Journal of the National Cancer Institute.

Findings

Investigators found that survivors had statistically significant lower total intelligence (P=0.001), verbal intelligence (P=0.02), and performance intelligence (P=0.007) quotients than controls.

They also found a negative correlation between CSF p-Tau, but not CSF Tau, levels and total intelligence (P=0.02), verbal intelligence (P=0.001), and performance intelligence (P=0.04) quotients.

Only performance intelligence was negatively correlated with total intrathecal methotrexate (P=0.007).

And because total intrathecal methotrexate dose and CSF p-Tau were not significantly correlated (P=0.29), the investigators believe intervening factors increase CSF p-Tau independently from methotrexate dose.

Results of subset tests revealed that cognitive flexibility (set-shifting and working memory), and processing speed were affected (P<0.05).

However, long-term memory, focused and sustained attention, and inhibition appeared unaffected (P>0.05).

The investigators believe these differences in vulnerability of cognitive functions parallel patient age at time of development.

For example, long-term memory, focused and sustained attention, and inhibition develop before children reach 6 years, the mean age at which the survivor cohort was diagnosed.

But set-shifting, working memory, and processing speed mature during adolescence, after the patients were diagnosed and treated.

Limitations of the study, according to the investigators, include its retrospective and cross-sectional design, the relatively small sample size, and the lack of pretreatment neurocognitive data.

Nevertheless, they believe the study should encourage the use of the CSF biomarker, intrathecal methotrexate dose, and age at therapy initiation in neurotoxicity assessments to identify children at risk for long-term sequelae.

"If we systematically measure these p-Tau levels in the future," Iris Elens, MD, also of KU Leuven, said, "we can offer specific help to children with high values. With early coaching aimed at the most relevant functions we can prevent problems that would otherwise manifest 10 to 15 years after the treatment."

The Olivia Hendrickx Research Fund supported the study. 

Photo courtesy of Columbia University

A small retrospective study of survivors of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) has found that phosphorylated Tau (p-Tau) in patients’ cerebrospinal fluid (CSF) is a predictor of late neurocognitive consequences.

Investigators compared intellectual performance, memory, and executive functioning between survivors and control subjects and observed that CSF levels of p-Tau during treatment and total intrathecal methotrexate dose negatively correlated with intellectual performance.

They suggest that identifying at-risk children early “could inspire interventions to prevent or remediate chemotherapy-induced cognitive sequelae.”

The investigators enrolled 31 nonirradiated adults, 27 who had had ALL and 4 NHL. They compared the survivors to 35 age-matched controls.

All study participants were a mean age of 21.5 years (range, 16.1–29.8). The mean age of the survivors at diagnosis was 6.4 years.

"Our team collected samples of brain fluid during the cancer treatment,” Rudi D’Hooge, PhD, of KU Leuven in Belgium, said. “We analyzed the p-Tau levels to measure the damage to the brain cells."

Investigators assessed intelligence, memory, and executive function using Wechsler Adult Intelligence Scale (WAIS IV), Rey Auditory Verbal Learning Test (AVLT), and Amsterdam Neuropsychological Tasks (ANT), respectively.

Statistical analysis included two-sided, one-way analysis of covariance (ANCOVA) with survivor group vs control group as an independent factor.  Parental socioeconomic status was a covariate.

Dr D’Hooge and colleagues published their findings in JNCI, the Journal of the National Cancer Institute.

Findings

Investigators found that survivors had statistically significant lower total intelligence (P=0.001), verbal intelligence (P=0.02), and performance intelligence (P=0.007) quotients than controls.

They also found a negative correlation between CSF p-Tau, but not CSF Tau, levels and total intelligence (P=0.02), verbal intelligence (P=0.001), and performance intelligence (P=0.04) quotients.

Only performance intelligence was negatively correlated with total intrathecal methotrexate (P=0.007).

And because total intrathecal methotrexate dose and CSF p-Tau were not significantly correlated (P=0.29), the investigators believe intervening factors increase CSF p-Tau independently from methotrexate dose.

Results of subset tests revealed that cognitive flexibility (set-shifting and working memory), and processing speed were affected (P<0.05).

However, long-term memory, focused and sustained attention, and inhibition appeared unaffected (P>0.05).

The investigators believe these differences in vulnerability of cognitive functions parallel patient age at time of development.

For example, long-term memory, focused and sustained attention, and inhibition develop before children reach 6 years, the mean age at which the survivor cohort was diagnosed.

But set-shifting, working memory, and processing speed mature during adolescence, after the patients were diagnosed and treated.

Limitations of the study, according to the investigators, include its retrospective and cross-sectional design, the relatively small sample size, and the lack of pretreatment neurocognitive data.

Nevertheless, they believe the study should encourage the use of the CSF biomarker, intrathecal methotrexate dose, and age at therapy initiation in neurotoxicity assessments to identify children at risk for long-term sequelae.

"If we systematically measure these p-Tau levels in the future," Iris Elens, MD, also of KU Leuven, said, "we can offer specific help to children with high values. With early coaching aimed at the most relevant functions we can prevent problems that would otherwise manifest 10 to 15 years after the treatment."

The Olivia Hendrickx Research Fund supported the study. 

At the undergraduate level, classes on medical ethics tend to focus on the big ticket items like abortion, euthanasia, and social justice. Personally, I find the more interesting clinical cases involve relatively minor issues that accumulate to create problems. Privacy is one example.

A large amount of information in the mother’s prenatal records potentially impacts a newborn’s care. Ideally, the EHR is transferring data to the newborn’s chart, but not everything automatically populates in the newborn record, so there will be times when a pediatrician needs to review the mother’s chart.

• The criteria for selecting which mothers’ charts to review involve racial profiling.
• Access to mental health records involving addiction treatment requires special authorization. State laws and hospital policies will vary.
• Mom is a Hollywood celebrity and, while reviewing her chart, prurient curiosity extends the search to records of her cosmetic surgeries.

In my opinion, most of what is and isn’t permissible is determined by medical custom and not by statutes. The judiciary reserves the power to intervene, so medical custom should be informed by laws and by legal principles. But, the primary basis for these decisions should be a commitment to patient advocacy and to common sense, which in this situation means, “Would the typical reasonable person be upset if she learned I had done something without telling her?” If the answer to that question is yes, or in any way equivocal, I think ethics would dictate obtaining consent or at least assent.

Opiate addiction has quadrupled in the past 15 years. Almost all states now have prescription registries to help detect doctor shopping, multiple prescribers, and misdirection. If you are prescribing an opiate, it is ethically reasonable (and now the law) for you to make writing the prescription contingent on your patient agreeing to your consulting the registry. No consent, no prescription.

I think the facts of that case (writing a prescription) can be distinguished (a legal term) from the case of a neonatologist accessing the narcotic registry of the mother while on a fishing expedition to find evidence that might help the baby. Perhaps it is okay with the mother’s uncoerced consent, but otherwise I think that practice reeks as an unreasonable search. Ethically and legally, it has parallels to Ferguson v. City of Charleston (SCOTUS 2001).

That was a 6-3 Supreme Court decision, so, while I agree with the majority, you may find hospital lawyers who disagree. Overall, I assert that consent and privacy are best considered ethically as advocacy for the patient and not as legalistic forms that the physician must complete.

The reverse situation also occurs. Sometimes maternal health information is placed into the newborn’s chart that doesn’t need to be there. For example, common practice has been to designate mom, after delivery, as G4P2022. This contains the information that mother has had two therapeutic abortions. Does that information belong in a newborn’s chart? Especially in the era of the EHR where this information will hang around forever and will be easily obtained by the baby 16 years later when she can access all her medical information online. Will the mother be upset for her teenage daughter to learn that mom has had two abortions? Is that private information, belonging to the mother, that was given in confidence to her obstetrician? I advocate respecting privacy.

I have similar concerns about STD information being transferred from maternal charts to the newborn’s EHR. A maternal history of gonorrhea treated 8 years previously is unlikely to be relevant and should not populate the newborn’s EHR. I can make an argument that chlamydia detected and treated during the pregnancy might be useful to the baby’s pediatrician because neither treatment nor tests of cure are perfect. Perhaps, it could exist as a Snapchat-type record and disappear from the newborn’s record in a year if no respiratory symptoms occur.

I’m aware of efforts to destigmatize abortion and STDs, but, until that occurs, sensitive information should be handled delicately to preserve privacy. That is a major component of the Hippocratic Oath.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis.

At the undergraduate level, classes on medical ethics tend to focus on the big ticket items like abortion, euthanasia, and social justice. Personally, I find the more interesting clinical cases involve relatively minor issues that accumulate to create problems. Privacy is one example.

A large amount of information in the mother’s prenatal records potentially impacts a newborn’s care. Ideally, the EHR is transferring data to the newborn’s chart, but not everything automatically populates in the newborn record, so there will be times when a pediatrician needs to review the mother’s chart.

• The criteria for selecting which mothers’ charts to review involve racial profiling.
• Access to mental health records involving addiction treatment requires special authorization. State laws and hospital policies will vary.
• Mom is a Hollywood celebrity and, while reviewing her chart, prurient curiosity extends the search to records of her cosmetic surgeries.

In my opinion, most of what is and isn’t permissible is determined by medical custom and not by statutes. The judiciary reserves the power to intervene, so medical custom should be informed by laws and by legal principles. But, the primary basis for these decisions should be a commitment to patient advocacy and to common sense, which in this situation means, “Would the typical reasonable person be upset if she learned I had done something without telling her?” If the answer to that question is yes, or in any way equivocal, I think ethics would dictate obtaining consent or at least assent.

Opiate addiction has quadrupled in the past 15 years. Almost all states now have prescription registries to help detect doctor shopping, multiple prescribers, and misdirection. If you are prescribing an opiate, it is ethically reasonable (and now the law) for you to make writing the prescription contingent on your patient agreeing to your consulting the registry. No consent, no prescription.

I think the facts of that case (writing a prescription) can be distinguished (a legal term) from the case of a neonatologist accessing the narcotic registry of the mother while on a fishing expedition to find evidence that might help the baby. Perhaps it is okay with the mother’s uncoerced consent, but otherwise I think that practice reeks as an unreasonable search. Ethically and legally, it has parallels to Ferguson v. City of Charleston (SCOTUS 2001).

That was a 6-3 Supreme Court decision, so, while I agree with the majority, you may find hospital lawyers who disagree. Overall, I assert that consent and privacy are best considered ethically as advocacy for the patient and not as legalistic forms that the physician must complete.

The reverse situation also occurs. Sometimes maternal health information is placed into the newborn’s chart that doesn’t need to be there. For example, common practice has been to designate mom, after delivery, as G4P2022. This contains the information that mother has had two therapeutic abortions. Does that information belong in a newborn’s chart? Especially in the era of the EHR where this information will hang around forever and will be easily obtained by the baby 16 years later when she can access all her medical information online. Will the mother be upset for her teenage daughter to learn that mom has had two abortions? Is that private information, belonging to the mother, that was given in confidence to her obstetrician? I advocate respecting privacy.

I have similar concerns about STD information being transferred from maternal charts to the newborn’s EHR. A maternal history of gonorrhea treated 8 years previously is unlikely to be relevant and should not populate the newborn’s EHR. I can make an argument that chlamydia detected and treated during the pregnancy might be useful to the baby’s pediatrician because neither treatment nor tests of cure are perfect. Perhaps, it could exist as a Snapchat-type record and disappear from the newborn’s record in a year if no respiratory symptoms occur.

I’m aware of efforts to destigmatize abortion and STDs, but, until that occurs, sensitive information should be handled delicately to preserve privacy. That is a major component of the Hippocratic Oath.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis.

At the undergraduate level, classes on medical ethics tend to focus on the big ticket items like abortion, euthanasia, and social justice. Personally, I find the more interesting clinical cases involve relatively minor issues that accumulate to create problems. Privacy is one example.

A large amount of information in the mother’s prenatal records potentially impacts a newborn’s care. Ideally, the EHR is transferring data to the newborn’s chart, but not everything automatically populates in the newborn record, so there will be times when a pediatrician needs to review the mother’s chart.

• The criteria for selecting which mothers’ charts to review involve racial profiling.
• Access to mental health records involving addiction treatment requires special authorization. State laws and hospital policies will vary.
• Mom is a Hollywood celebrity and, while reviewing her chart, prurient curiosity extends the search to records of her cosmetic surgeries.

In my opinion, most of what is and isn’t permissible is determined by medical custom and not by statutes. The judiciary reserves the power to intervene, so medical custom should be informed by laws and by legal principles. But, the primary basis for these decisions should be a commitment to patient advocacy and to common sense, which in this situation means, “Would the typical reasonable person be upset if she learned I had done something without telling her?” If the answer to that question is yes, or in any way equivocal, I think ethics would dictate obtaining consent or at least assent.

Opiate addiction has quadrupled in the past 15 years. Almost all states now have prescription registries to help detect doctor shopping, multiple prescribers, and misdirection. If you are prescribing an opiate, it is ethically reasonable (and now the law) for you to make writing the prescription contingent on your patient agreeing to your consulting the registry. No consent, no prescription.

I think the facts of that case (writing a prescription) can be distinguished (a legal term) from the case of a neonatologist accessing the narcotic registry of the mother while on a fishing expedition to find evidence that might help the baby. Perhaps it is okay with the mother’s uncoerced consent, but otherwise I think that practice reeks as an unreasonable search. Ethically and legally, it has parallels to Ferguson v. City of Charleston (SCOTUS 2001).

That was a 6-3 Supreme Court decision, so, while I agree with the majority, you may find hospital lawyers who disagree. Overall, I assert that consent and privacy are best considered ethically as advocacy for the patient and not as legalistic forms that the physician must complete.

The reverse situation also occurs. Sometimes maternal health information is placed into the newborn’s chart that doesn’t need to be there. For example, common practice has been to designate mom, after delivery, as G4P2022. This contains the information that mother has had two therapeutic abortions. Does that information belong in a newborn’s chart? Especially in the era of the EHR where this information will hang around forever and will be easily obtained by the baby 16 years later when she can access all her medical information online. Will the mother be upset for her teenage daughter to learn that mom has had two abortions? Is that private information, belonging to the mother, that was given in confidence to her obstetrician? I advocate respecting privacy.

I have similar concerns about STD information being transferred from maternal charts to the newborn’s EHR. A maternal history of gonorrhea treated 8 years previously is unlikely to be relevant and should not populate the newborn’s EHR. I can make an argument that chlamydia detected and treated during the pregnancy might be useful to the baby’s pediatrician because neither treatment nor tests of cure are perfect. Perhaps, it could exist as a Snapchat-type record and disappear from the newborn’s record in a year if no respiratory symptoms occur.

I’m aware of efforts to destigmatize abortion and STDs, but, until that occurs, sensitive information should be handled delicately to preserve privacy. That is a major component of the Hippocratic Oath.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis.

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Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

NONESTROGEN PRODUCT FOR DYSPAREUNIA

FOR MORE INFORMATION, VISIT: http://www.amagpharma.com

ORAL MAINTENANCE TX FOR RECURRENT CANCER

FOR MORE INFORMATION, VISIT: http://www.zejula.com

MIGS STAPLING SYSTEM WITH REAL-TIME FEEDBACK

FOR MORE INFORMATION, VISIT: http://www.medtronic.com

BONE BUILDING AGENT

FOR MORE INFORMATION, VISIT: http://www.radiuspharm.com

PROTEOMIC BREAST CANCER ASSAY

FOR MORE INFORMATION, VISIT: http://www.provistadx.com

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

NONESTROGEN PRODUCT FOR DYSPAREUNIA

FOR MORE INFORMATION, VISIT: http://www.amagpharma.com

ORAL MAINTENANCE TX FOR RECURRENT CANCER

FOR MORE INFORMATION, VISIT: http://www.zejula.com

MIGS STAPLING SYSTEM WITH REAL-TIME FEEDBACK

FOR MORE INFORMATION, VISIT: http://www.medtronic.com

BONE BUILDING AGENT

FOR MORE INFORMATION, VISIT: http://www.radiuspharm.com

PROTEOMIC BREAST CANCER ASSAY

FOR MORE INFORMATION, VISIT: http://www.provistadx.com

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

“Therapeutic patient education” (TPE) is a new paradigm that addresses less than optimal outcomes in patients with atopic dermatitis (AD) resulting from poor adherence to treatment.

The aim of TPE, a multidisciplinary approach to caring for and managing AD, is to improve patient and caregiver adherence to physician-directed treatments through education and to improve quality of life, according to several presenters who spoke at a pediatric dermatology meeting sponsored by Rady Children’s Hospital–San Diego and University of California, San Diego. They reviewed the approach to using TPE in chronic disease states, demonstrating this state-of-the-art approach to educating patients, families, and health care providers about AD management, and allowing for the exchange of ideas for best practices on AD therapeutic education programs and use in the U.S. health care environment.

Other successful meetings on TPE in Europe, Asia, and South America inspired this meeting, the first in the United States aimed to train health care professionals in TPE principles for AD. The meeting was sponsored by the Fondation Dermatite Atopique (Atopic Dermatitis Foundation for Research and Education), Rady’s Eczema and Inflammatory Skin Disease Center, and UCSD.

TPE is defined by the World Health Organization as an approach to help patients with chronic illness acquire or maintain the skills necessary to manage their life and illness in the best way possible. TPE involves patient preferences, shared decision-making, organized activities, psychosocial support, hospital organization and procedures, and health- and disease-related behaviors.

Sébastien Barbarot, MD, of the departments of dermatology and pediatric dermatology, Nantes (France) University Hospital, said that there are four main components to the TPE process:

• Assessing and understanding the patient’s knowledge and values.

• Developing age-appropriate personalized educational objectives.

• Transferring the necessary skills to the patient or caregiver.

• Assessing the effectiveness of the educational program.

Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at UCSD, discussed how to conduct the initial visit with potential candidates for TPE. At the new patient visit, the pediatric patient and their caregivers should first be presented with the concept of TPE, which includes proposing a personalized education approach. Next, explain the goals and benefits of TPE (with a time and location for the sessions), provide educational materials, allow time for questions, and establish the patient’s consent to participate.

[email protected]

“Therapeutic patient education” (TPE) is a new paradigm that addresses less than optimal outcomes in patients with atopic dermatitis (AD) resulting from poor adherence to treatment.

The aim of TPE, a multidisciplinary approach to caring for and managing AD, is to improve patient and caregiver adherence to physician-directed treatments through education and to improve quality of life, according to several presenters who spoke at a pediatric dermatology meeting sponsored by Rady Children’s Hospital–San Diego and University of California, San Diego. They reviewed the approach to using TPE in chronic disease states, demonstrating this state-of-the-art approach to educating patients, families, and health care providers about AD management, and allowing for the exchange of ideas for best practices on AD therapeutic education programs and use in the U.S. health care environment.

Other successful meetings on TPE in Europe, Asia, and South America inspired this meeting, the first in the United States aimed to train health care professionals in TPE principles for AD. The meeting was sponsored by the Fondation Dermatite Atopique (Atopic Dermatitis Foundation for Research and Education), Rady’s Eczema and Inflammatory Skin Disease Center, and UCSD.

TPE is defined by the World Health Organization as an approach to help patients with chronic illness acquire or maintain the skills necessary to manage their life and illness in the best way possible. TPE involves patient preferences, shared decision-making, organized activities, psychosocial support, hospital organization and procedures, and health- and disease-related behaviors.

Sébastien Barbarot, MD, of the departments of dermatology and pediatric dermatology, Nantes (France) University Hospital, said that there are four main components to the TPE process:

• Assessing and understanding the patient’s knowledge and values.

• Developing age-appropriate personalized educational objectives.

• Transferring the necessary skills to the patient or caregiver.

• Assessing the effectiveness of the educational program.

Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at UCSD, discussed how to conduct the initial visit with potential candidates for TPE. At the new patient visit, the pediatric patient and their caregivers should first be presented with the concept of TPE, which includes proposing a personalized education approach. Next, explain the goals and benefits of TPE (with a time and location for the sessions), provide educational materials, allow time for questions, and establish the patient’s consent to participate.

[email protected]

“Therapeutic patient education” (TPE) is a new paradigm that addresses less than optimal outcomes in patients with atopic dermatitis (AD) resulting from poor adherence to treatment.

The aim of TPE, a multidisciplinary approach to caring for and managing AD, is to improve patient and caregiver adherence to physician-directed treatments through education and to improve quality of life, according to several presenters who spoke at a pediatric dermatology meeting sponsored by Rady Children’s Hospital–San Diego and University of California, San Diego. They reviewed the approach to using TPE in chronic disease states, demonstrating this state-of-the-art approach to educating patients, families, and health care providers about AD management, and allowing for the exchange of ideas for best practices on AD therapeutic education programs and use in the U.S. health care environment.

Other successful meetings on TPE in Europe, Asia, and South America inspired this meeting, the first in the United States aimed to train health care professionals in TPE principles for AD. The meeting was sponsored by the Fondation Dermatite Atopique (Atopic Dermatitis Foundation for Research and Education), Rady’s Eczema and Inflammatory Skin Disease Center, and UCSD.

TPE is defined by the World Health Organization as an approach to help patients with chronic illness acquire or maintain the skills necessary to manage their life and illness in the best way possible. TPE involves patient preferences, shared decision-making, organized activities, psychosocial support, hospital organization and procedures, and health- and disease-related behaviors.

Sébastien Barbarot, MD, of the departments of dermatology and pediatric dermatology, Nantes (France) University Hospital, said that there are four main components to the TPE process:

• Assessing and understanding the patient’s knowledge and values.

• Developing age-appropriate personalized educational objectives.

• Transferring the necessary skills to the patient or caregiver.

• Assessing the effectiveness of the educational program.

Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at UCSD, discussed how to conduct the initial visit with potential candidates for TPE. At the new patient visit, the pediatric patient and their caregivers should first be presented with the concept of TPE, which includes proposing a personalized education approach. Next, explain the goals and benefits of TPE (with a time and location for the sessions), provide educational materials, allow time for questions, and establish the patient’s consent to participate.

[email protected]

MADRID – The introduction of immune checkpoint inhibitor drugs has “been great for cancer but bad for rheumatology.”

That’s the gist of the immunologic adverse effect fallout from the immunomodulatory revolution that’s recently swept oncology, Leonard Calabrese, DO, said in a video interview during the European Congress of Rheumatology.

Results from a recent survey of U.S. rheumatologists run by Dr. Calabrese and his associates showed that “more than a quarter” now have seen at least one patient who experienced activation of a rheumatologic disease after starting treatment with an immune checkpoint inhibitor, said Dr. Calabrese, head of the section of clinical immunology at the Cleveland Clinic in Ohio.

Unlike most other immunological adverse effects caused by immune checkpoint inhibitors, the rheumatologic complications usually don’t resolve when treatment stops, he added.

These adverse effects represent a new wrinkle for the practice of rheumatology and are now something that clinicians must familiarize themselves with, Dr. Calabrese advised.

Dr. Calabrese reported that he is a consultant to Bristol-Myers Squibb.

[email protected]

On Twitter @mitchelzoler

MADRID – The introduction of immune checkpoint inhibitor drugs has “been great for cancer but bad for rheumatology.”

That’s the gist of the immunologic adverse effect fallout from the immunomodulatory revolution that’s recently swept oncology, Leonard Calabrese, DO, said in a video interview during the European Congress of Rheumatology.

Results from a recent survey of U.S. rheumatologists run by Dr. Calabrese and his associates showed that “more than a quarter” now have seen at least one patient who experienced activation of a rheumatologic disease after starting treatment with an immune checkpoint inhibitor, said Dr. Calabrese, head of the section of clinical immunology at the Cleveland Clinic in Ohio.

Unlike most other immunological adverse effects caused by immune checkpoint inhibitors, the rheumatologic complications usually don’t resolve when treatment stops, he added.

These adverse effects represent a new wrinkle for the practice of rheumatology and are now something that clinicians must familiarize themselves with, Dr. Calabrese advised.

Dr. Calabrese reported that he is a consultant to Bristol-Myers Squibb.

[email protected]

On Twitter @mitchelzoler

MADRID – The introduction of immune checkpoint inhibitor drugs has “been great for cancer but bad for rheumatology.”

That’s the gist of the immunologic adverse effect fallout from the immunomodulatory revolution that’s recently swept oncology, Leonard Calabrese, DO, said in a video interview during the European Congress of Rheumatology.

Results from a recent survey of U.S. rheumatologists run by Dr. Calabrese and his associates showed that “more than a quarter” now have seen at least one patient who experienced activation of a rheumatologic disease after starting treatment with an immune checkpoint inhibitor, said Dr. Calabrese, head of the section of clinical immunology at the Cleveland Clinic in Ohio.

Unlike most other immunological adverse effects caused by immune checkpoint inhibitors, the rheumatologic complications usually don’t resolve when treatment stops, he added.

These adverse effects represent a new wrinkle for the practice of rheumatology and are now something that clinicians must familiarize themselves with, Dr. Calabrese advised.

Dr. Calabrese reported that he is a consultant to Bristol-Myers Squibb.

[email protected]

On Twitter @mitchelzoler

CHICAGO – High-dose vitamin D supplementation is a simple, safe approach for improving on the efficacy of first-line chemotherapy for metastatic colorectal cancer, suggest findings of the SUNSHINE trial reported at the annual meeting of the American Society of Clinical Oncology.

“Vitamin D has shown anti-neoplastic properties in the laboratory, including inhibition of cell proliferation and angiogenesis, induction of cell differentiation and apoptosis, as well as anti-inflammatory and immunomodulatory effects,” said lead author Kimmie Ng, MD, director of clinical research and a Gastrointestinal Cancer Center physician at the Dana-Farber Cancer Institute in Boston.

“The vitamin D hypothesis is also supported by a large body of epidemiologic evidence, both from our group as well as from others, that have shown that higher plasma 25-hydroxyvitamin D levels are associated with improved survival in patients with colorectal cancer,” she added.

Notably, in the CALGB/SWOG 80405 trial of first-line therapy for colorectal cancer, patients’ median 25-hydroxy vitamin D level at baseline fell below the cutoff for deficiency (ASCO 2015 meeting, Abstract 3503). Moreover, those having higher levels ultimately had better overall survival even after other factors were taken into account.

In the SUNSHINE trial, the investigators studied 139 patients with untreated metastatic colorectal cancer. Results showed that those given FOLFOX chemotherapy and the antiangiogenic agent bevacizumab (Avastin) plus high-dose vitamin D had a one-third lower risk of progression or death compared with counterparts given the same regimen plus low-dose vitamin D.

High-dose supplementation was not associated with greater toxicity. In fact, patients in that group had a much lower incidence of grade 3 or 4 diarrhea.

“After a decade of observational data linking higher vitamin D status with improved outcomes in colorectal cancer patients, SUNSHINE is the first completed randomized double-blind controlled clinical trial of vitamin D supplementation for treatment of colorectal cancer,” Dr. Ng said. “The trial met its primary endpoint. Given this data, a larger, confirmatory phase III trial is warranted.”

The investigators are performing subgroup analyses and analyzing overall survival, and will measure patients’ 25-hydroxyvitamin D levels in plasma samples collected serially throughout the study to determine whether they correlate with outcomes.

In addition, “to help understand and elucidate underlying mechanisms and biology, we have planned several correlative studies looking at tumoral and plasma biomarkers related to the vitamin D pathway, inflammation, and tumor immunity, among other pathways,” she further noted. “We will also be conducting next-generation sequencing and gene expression analyses.”

Expert perspective

“It will be interesting to know [patients’ vitamin D levels] as the majority of patients were enrolled in New England, where I think there is a little less sunshine than in other parts of the United States, so perhaps the vitamin D levels will reflect that,” said invited discussant Andrea Cercek, MD, of Memorial Sloan Kettering Cancer Center in New York.

Data on vitamin D pertaining to chemoprevention and to outcomes in other malignancies have been mixed, she cautioned. For example, supplementation did not reduce the risk of recurrent colorectal adenomas in one study (N Engl J Med. 2015;373:1519-30), and benefit or harm in terms of developing advanced colorectal adenomas in another study hinged on vitamin D receptor genotype (JAMA Oncol. 2017;3:628-35). Among patients with prostate cancer, addition of vitamin D to chemotherapy was actually associated with poorer overall survival (J Clin Oncol. 2011;29:2191-8).

“SUNSHINE was a positive study. It was a very well carried out phase II trial with a significant progression-free survival benefit. Correlative analyses are ongoing, and these will be critical, looking at biomarkers, perhaps helping us identify those patients who will benefit,” Dr. Cercek summarized. “I agree 100% with the investigators that a phase III study is warranted, and I look forward to it.”

Study details

Patients in SUNSHINE were randomized to receive first-line modified FOLFOX chemotherapy and bevacizumab plus either high-dose vitamin D (oral vitamin D3 8,000 IU/day for 2 weeks as a loading dose, followed by 4,000 IU/day) or low-dose vitamin D (oral vitamin D3 400 IU/day) on a double-blind basis. The latter “is an amount you would find in a multivitamin and only increases plasma levels by about 3 ng/mL, thus serving as a useful active control” Dr. Ng noted.

Receipt of chemotherapy and bevacizumab was generally similar between groups. “It is interesting to note that more patients receiving high-dose vitamin D discontinued treatment to undergo potentially curative surgery compared to those in the control arm, though this was not statistically different,” she noted.

In intent-to-treat analysis conducted at a median follow-up of 17-18 months, progression-free survival, the trial’s primary endpoint, was a median of 13.1 months in the high-dose group and 11.2 months in the low-dose group (P = .04). The difference in favor of high-dose vitamin D remained significant in multivariate analysis (hazard ratio, 0.67; P = .02).

The groups were statistically indistinguishable with respect to overall response rate, but the disease control rate was marginally better with high-dose versus low-dose vitamin D (96% vs. 84%, P = .05).

Rates of most grade 3 or 4 adverse events did not differ significantly between groups. However, diarrhea of these grades was less common in the high-dose vitamin D group (1% vs. 12%; P = .02). With respect to grade 3 or 4 events possibly related to the vitamin therapy, there was one case of hyperphosphatemia in the high-dose group and one case of kidney stones in the low-dose group.

Dr. Ng disclosed that she receives honoraria from Prime Oncology and Sage Publications; has a consulting or advisory role with Defined Health and Genentech/Roche; and receives research funding from Celgene, Genentech/Roche (institutional), Gilead Sciences, Pharmavite (institutional), and Trovagene.

CHICAGO – High-dose vitamin D supplementation is a simple, safe approach for improving on the efficacy of first-line chemotherapy for metastatic colorectal cancer, suggest findings of the SUNSHINE trial reported at the annual meeting of the American Society of Clinical Oncology.

“Vitamin D has shown anti-neoplastic properties in the laboratory, including inhibition of cell proliferation and angiogenesis, induction of cell differentiation and apoptosis, as well as anti-inflammatory and immunomodulatory effects,” said lead author Kimmie Ng, MD, director of clinical research and a Gastrointestinal Cancer Center physician at the Dana-Farber Cancer Institute in Boston.

“The vitamin D hypothesis is also supported by a large body of epidemiologic evidence, both from our group as well as from others, that have shown that higher plasma 25-hydroxyvitamin D levels are associated with improved survival in patients with colorectal cancer,” she added.

Notably, in the CALGB/SWOG 80405 trial of first-line therapy for colorectal cancer, patients’ median 25-hydroxy vitamin D level at baseline fell below the cutoff for deficiency (ASCO 2015 meeting, Abstract 3503). Moreover, those having higher levels ultimately had better overall survival even after other factors were taken into account.

In the SUNSHINE trial, the investigators studied 139 patients with untreated metastatic colorectal cancer. Results showed that those given FOLFOX chemotherapy and the antiangiogenic agent bevacizumab (Avastin) plus high-dose vitamin D had a one-third lower risk of progression or death compared with counterparts given the same regimen plus low-dose vitamin D.

High-dose supplementation was not associated with greater toxicity. In fact, patients in that group had a much lower incidence of grade 3 or 4 diarrhea.

“After a decade of observational data linking higher vitamin D status with improved outcomes in colorectal cancer patients, SUNSHINE is the first completed randomized double-blind controlled clinical trial of vitamin D supplementation for treatment of colorectal cancer,” Dr. Ng said. “The trial met its primary endpoint. Given this data, a larger, confirmatory phase III trial is warranted.”

The investigators are performing subgroup analyses and analyzing overall survival, and will measure patients’ 25-hydroxyvitamin D levels in plasma samples collected serially throughout the study to determine whether they correlate with outcomes.

In addition, “to help understand and elucidate underlying mechanisms and biology, we have planned several correlative studies looking at tumoral and plasma biomarkers related to the vitamin D pathway, inflammation, and tumor immunity, among other pathways,” she further noted. “We will also be conducting next-generation sequencing and gene expression analyses.”

Expert perspective

“It will be interesting to know [patients’ vitamin D levels] as the majority of patients were enrolled in New England, where I think there is a little less sunshine than in other parts of the United States, so perhaps the vitamin D levels will reflect that,” said invited discussant Andrea Cercek, MD, of Memorial Sloan Kettering Cancer Center in New York.

Data on vitamin D pertaining to chemoprevention and to outcomes in other malignancies have been mixed, she cautioned. For example, supplementation did not reduce the risk of recurrent colorectal adenomas in one study (N Engl J Med. 2015;373:1519-30), and benefit or harm in terms of developing advanced colorectal adenomas in another study hinged on vitamin D receptor genotype (JAMA Oncol. 2017;3:628-35). Among patients with prostate cancer, addition of vitamin D to chemotherapy was actually associated with poorer overall survival (J Clin Oncol. 2011;29:2191-8).

“SUNSHINE was a positive study. It was a very well carried out phase II trial with a significant progression-free survival benefit. Correlative analyses are ongoing, and these will be critical, looking at biomarkers, perhaps helping us identify those patients who will benefit,” Dr. Cercek summarized. “I agree 100% with the investigators that a phase III study is warranted, and I look forward to it.”

Study details

Patients in SUNSHINE were randomized to receive first-line modified FOLFOX chemotherapy and bevacizumab plus either high-dose vitamin D (oral vitamin D3 8,000 IU/day for 2 weeks as a loading dose, followed by 4,000 IU/day) or low-dose vitamin D (oral vitamin D3 400 IU/day) on a double-blind basis. The latter “is an amount you would find in a multivitamin and only increases plasma levels by about 3 ng/mL, thus serving as a useful active control” Dr. Ng noted.

Receipt of chemotherapy and bevacizumab was generally similar between groups. “It is interesting to note that more patients receiving high-dose vitamin D discontinued treatment to undergo potentially curative surgery compared to those in the control arm, though this was not statistically different,” she noted.

In intent-to-treat analysis conducted at a median follow-up of 17-18 months, progression-free survival, the trial’s primary endpoint, was a median of 13.1 months in the high-dose group and 11.2 months in the low-dose group (P = .04). The difference in favor of high-dose vitamin D remained significant in multivariate analysis (hazard ratio, 0.67; P = .02).

The groups were statistically indistinguishable with respect to overall response rate, but the disease control rate was marginally better with high-dose versus low-dose vitamin D (96% vs. 84%, P = .05).

Rates of most grade 3 or 4 adverse events did not differ significantly between groups. However, diarrhea of these grades was less common in the high-dose vitamin D group (1% vs. 12%; P = .02). With respect to grade 3 or 4 events possibly related to the vitamin therapy, there was one case of hyperphosphatemia in the high-dose group and one case of kidney stones in the low-dose group.

Dr. Ng disclosed that she receives honoraria from Prime Oncology and Sage Publications; has a consulting or advisory role with Defined Health and Genentech/Roche; and receives research funding from Celgene, Genentech/Roche (institutional), Gilead Sciences, Pharmavite (institutional), and Trovagene.

CHICAGO – High-dose vitamin D supplementation is a simple, safe approach for improving on the efficacy of first-line chemotherapy for metastatic colorectal cancer, suggest findings of the SUNSHINE trial reported at the annual meeting of the American Society of Clinical Oncology.

“Vitamin D has shown anti-neoplastic properties in the laboratory, including inhibition of cell proliferation and angiogenesis, induction of cell differentiation and apoptosis, as well as anti-inflammatory and immunomodulatory effects,” said lead author Kimmie Ng, MD, director of clinical research and a Gastrointestinal Cancer Center physician at the Dana-Farber Cancer Institute in Boston.

“The vitamin D hypothesis is also supported by a large body of epidemiologic evidence, both from our group as well as from others, that have shown that higher plasma 25-hydroxyvitamin D levels are associated with improved survival in patients with colorectal cancer,” she added.

Notably, in the CALGB/SWOG 80405 trial of first-line therapy for colorectal cancer, patients’ median 25-hydroxy vitamin D level at baseline fell below the cutoff for deficiency (ASCO 2015 meeting, Abstract 3503). Moreover, those having higher levels ultimately had better overall survival even after other factors were taken into account.

In the SUNSHINE trial, the investigators studied 139 patients with untreated metastatic colorectal cancer. Results showed that those given FOLFOX chemotherapy and the antiangiogenic agent bevacizumab (Avastin) plus high-dose vitamin D had a one-third lower risk of progression or death compared with counterparts given the same regimen plus low-dose vitamin D.

High-dose supplementation was not associated with greater toxicity. In fact, patients in that group had a much lower incidence of grade 3 or 4 diarrhea.

“After a decade of observational data linking higher vitamin D status with improved outcomes in colorectal cancer patients, SUNSHINE is the first completed randomized double-blind controlled clinical trial of vitamin D supplementation for treatment of colorectal cancer,” Dr. Ng said. “The trial met its primary endpoint. Given this data, a larger, confirmatory phase III trial is warranted.”

The investigators are performing subgroup analyses and analyzing overall survival, and will measure patients’ 25-hydroxyvitamin D levels in plasma samples collected serially throughout the study to determine whether they correlate with outcomes.

In addition, “to help understand and elucidate underlying mechanisms and biology, we have planned several correlative studies looking at tumoral and plasma biomarkers related to the vitamin D pathway, inflammation, and tumor immunity, among other pathways,” she further noted. “We will also be conducting next-generation sequencing and gene expression analyses.”

Expert perspective

“It will be interesting to know [patients’ vitamin D levels] as the majority of patients were enrolled in New England, where I think there is a little less sunshine than in other parts of the United States, so perhaps the vitamin D levels will reflect that,” said invited discussant Andrea Cercek, MD, of Memorial Sloan Kettering Cancer Center in New York.

Data on vitamin D pertaining to chemoprevention and to outcomes in other malignancies have been mixed, she cautioned. For example, supplementation did not reduce the risk of recurrent colorectal adenomas in one study (N Engl J Med. 2015;373:1519-30), and benefit or harm in terms of developing advanced colorectal adenomas in another study hinged on vitamin D receptor genotype (JAMA Oncol. 2017;3:628-35). Among patients with prostate cancer, addition of vitamin D to chemotherapy was actually associated with poorer overall survival (J Clin Oncol. 2011;29:2191-8).

“SUNSHINE was a positive study. It was a very well carried out phase II trial with a significant progression-free survival benefit. Correlative analyses are ongoing, and these will be critical, looking at biomarkers, perhaps helping us identify those patients who will benefit,” Dr. Cercek summarized. “I agree 100% with the investigators that a phase III study is warranted, and I look forward to it.”

Study details

Patients in SUNSHINE were randomized to receive first-line modified FOLFOX chemotherapy and bevacizumab plus either high-dose vitamin D (oral vitamin D3 8,000 IU/day for 2 weeks as a loading dose, followed by 4,000 IU/day) or low-dose vitamin D (oral vitamin D3 400 IU/day) on a double-blind basis. The latter “is an amount you would find in a multivitamin and only increases plasma levels by about 3 ng/mL, thus serving as a useful active control” Dr. Ng noted.

Receipt of chemotherapy and bevacizumab was generally similar between groups. “It is interesting to note that more patients receiving high-dose vitamin D discontinued treatment to undergo potentially curative surgery compared to those in the control arm, though this was not statistically different,” she noted.

In intent-to-treat analysis conducted at a median follow-up of 17-18 months, progression-free survival, the trial’s primary endpoint, was a median of 13.1 months in the high-dose group and 11.2 months in the low-dose group (P = .04). The difference in favor of high-dose vitamin D remained significant in multivariate analysis (hazard ratio, 0.67; P = .02).

The groups were statistically indistinguishable with respect to overall response rate, but the disease control rate was marginally better with high-dose versus low-dose vitamin D (96% vs. 84%, P = .05).

Rates of most grade 3 or 4 adverse events did not differ significantly between groups. However, diarrhea of these grades was less common in the high-dose vitamin D group (1% vs. 12%; P = .02). With respect to grade 3 or 4 events possibly related to the vitamin therapy, there was one case of hyperphosphatemia in the high-dose group and one case of kidney stones in the low-dose group.

Dr. Ng disclosed that she receives honoraria from Prime Oncology and Sage Publications; has a consulting or advisory role with Defined Health and Genentech/Roche; and receives research funding from Celgene, Genentech/Roche (institutional), Gilead Sciences, Pharmavite (institutional), and Trovagene.

SAN FRANCISCO – When the Infectious Diseases Society of America released the “Bad Bugs, No Drugs” report in 2004, its authors warned that effective antibiotics may not be available to treat seriously ill patients in the near future.

It also proposed legislative, regulatory, and funding solutions with a goal of developing and licensing 10 new antibiotics by the year 2020.

One such advancement was the Generating Antibiotics Incentives Now Act, which was signed into law in 2012 and created a designation for new antibiotics that are used to treat serious and/or life-threatening diseases due to certain pathogens. It also extends the patent life of these antibiotics and allows for fast-track Food and Drug Administration approval.

[email protected]

SAN FRANCISCO – When the Infectious Diseases Society of America released the “Bad Bugs, No Drugs” report in 2004, its authors warned that effective antibiotics may not be available to treat seriously ill patients in the near future.

It also proposed legislative, regulatory, and funding solutions with a goal of developing and licensing 10 new antibiotics by the year 2020.

One such advancement was the Generating Antibiotics Incentives Now Act, which was signed into law in 2012 and created a designation for new antibiotics that are used to treat serious and/or life-threatening diseases due to certain pathogens. It also extends the patent life of these antibiotics and allows for fast-track Food and Drug Administration approval.

[email protected]

SAN FRANCISCO – When the Infectious Diseases Society of America released the “Bad Bugs, No Drugs” report in 2004, its authors warned that effective antibiotics may not be available to treat seriously ill patients in the near future.

It also proposed legislative, regulatory, and funding solutions with a goal of developing and licensing 10 new antibiotics by the year 2020.

One such advancement was the Generating Antibiotics Incentives Now Act, which was signed into law in 2012 and created a designation for new antibiotics that are used to treat serious and/or life-threatening diseases due to certain pathogens. It also extends the patent life of these antibiotics and allows for fast-track Food and Drug Administration approval.

[email protected]

LUGANO, SWITZERLAND – A combination of the Bruton’s tyrosine kinase (BTK) ibrutinib (Imbruvica) and the pan-phosphoinositide 3-kinase (PI3K) inhibitor buparlisib showed clinical activity superior to that of single-agent ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL).

In a phase I/IB dose escalation study and expansion cohort testing the combination in patients with diffuse large B cell lymphoma (DLBCL), follicular lymphoma, and MCL, the overall response rate (ORR) among patients with MCL was 100%, consisting of complete responses (CR) in 8 of 11 patients, and partial responses (PR) in 3 patients, reported Connie Lee Batlevi, MD, of Memorial Sloan Kettering Cancer Center in New York.

LUGANO, SWITZERLAND – A combination of the Bruton’s tyrosine kinase (BTK) ibrutinib (Imbruvica) and the pan-phosphoinositide 3-kinase (PI3K) inhibitor buparlisib showed clinical activity superior to that of single-agent ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL).

In a phase I/IB dose escalation study and expansion cohort testing the combination in patients with diffuse large B cell lymphoma (DLBCL), follicular lymphoma, and MCL, the overall response rate (ORR) among patients with MCL was 100%, consisting of complete responses (CR) in 8 of 11 patients, and partial responses (PR) in 3 patients, reported Connie Lee Batlevi, MD, of Memorial Sloan Kettering Cancer Center in New York.

LUGANO, SWITZERLAND – A combination of the Bruton’s tyrosine kinase (BTK) ibrutinib (Imbruvica) and the pan-phosphoinositide 3-kinase (PI3K) inhibitor buparlisib showed clinical activity superior to that of single-agent ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL).

In a phase I/IB dose escalation study and expansion cohort testing the combination in patients with diffuse large B cell lymphoma (DLBCL), follicular lymphoma, and MCL, the overall response rate (ORR) among patients with MCL was 100%, consisting of complete responses (CR) in 8 of 11 patients, and partial responses (PR) in 3 patients, reported Connie Lee Batlevi, MD, of Memorial Sloan Kettering Cancer Center in New York.

LAS VEGAS – Patients with medial compartment knee osteoarthritis who wore a patented flexible mobility shoe experienced a favorable reduction in medial tibial bone mineral density that directly correlated with their improved gait biomechanics and reduced peak knee adduction moment, Najia Shakoor, MD, reported at the World Congress on Osteoarthritis.

“Our results suggest that bone can be modified with sustained load reduction and that evaluation of tibial bone density may be an inexpensive tool for evaluating the consequences of load-reducing interventions,” said Dr. Shakoor, a rheumatologist at Rush University in Chicago.

Indeed, measuring changes in medial tibial bone density over time via serial dual x-ray absorptiometry is an attractive surrogate anatomic marker of a patient’s response to a biomechanical load-reducing intervention such as a special shoe or knee brace, Dr. Shakoor noted at the meeting sponsored by the Osteoarthritis Research Society International.

After all, she added, bone density measurement is simpler than sending a patient to a motion analysis laboratory for multicamera gait analysis using a force plate to evaluate changes in the peak external knee adduction moment (a validated marker of load distribution across the tibial plateau).

Studies suggest that bone, not cartilage, bears the bulk of the load burden across the knee joint. That’s why patients with knee osteoarthritis have increased proximal tibial bone mineral density. Dr. Shakoor presented evidence that sustained reduction in dynamic knee loading results in a proportionate reduction in medial tibial bone density over the course of 6 months.

She reported on 51 patients with mild to moderate radiographic and symptomatic medial compartment knee osteoarthritis who were randomized to wear a commercially available flexible mobility shoe or a similar-looking but nonflexible control shoe for 6 hours per day for at least 6 days per week for 6 months. At baseline and again at 6 months, the participants underwent knee bone density measurement and formal gait analysis.

Peak knee adduction moment decreased by 14% over the course of 6 months in the flexible shoe group, significantly greater than the 6% reduction in the controls. Moreover, Dr. Shakoor and her coinvestigators documented a significant reduction in medial tibial bone density in the flexible shoe group. The greater the improvement in knee adduction moment, the larger the reduction in bone density.

In contrast, medial tibial bone density didn’t change significantly in the controls.

Dr. Shakoor said that she had also expected to see a reduction in the ratio of medial to lateral tibial bone density in the flexible shoe group. However, there was no statistically significant change, although there was a trend in that direction.

Asked if reduction in knee adduction moment and/or medial tibial bone density correlated with improved knee pain scores, Dr. Shakoor replied that almost everyone in the study reported improvement in pain, suggesting a placebo effect for that endpoint. In any event, the relatively small study wasn’t powered to evaluate change in pain over time.

The Arthritis Foundation funded the study. Dr. Shakoor is coinventor of the flexible shoe used in the study. The patent, owned by Rush University, has been licensed to Dr. Comfort, which markets the shoe as the Dr. Comfort Flex-OA Mobility Shoe. A percentage of the proceeds from shoe sales is distributed to the university and the coinventors.

[email protected]

LAS VEGAS – Patients with medial compartment knee osteoarthritis who wore a patented flexible mobility shoe experienced a favorable reduction in medial tibial bone mineral density that directly correlated with their improved gait biomechanics and reduced peak knee adduction moment, Najia Shakoor, MD, reported at the World Congress on Osteoarthritis.

“Our results suggest that bone can be modified with sustained load reduction and that evaluation of tibial bone density may be an inexpensive tool for evaluating the consequences of load-reducing interventions,” said Dr. Shakoor, a rheumatologist at Rush University in Chicago.

Indeed, measuring changes in medial tibial bone density over time via serial dual x-ray absorptiometry is an attractive surrogate anatomic marker of a patient’s response to a biomechanical load-reducing intervention such as a special shoe or knee brace, Dr. Shakoor noted at the meeting sponsored by the Osteoarthritis Research Society International.

After all, she added, bone density measurement is simpler than sending a patient to a motion analysis laboratory for multicamera gait analysis using a force plate to evaluate changes in the peak external knee adduction moment (a validated marker of load distribution across the tibial plateau).

Studies suggest that bone, not cartilage, bears the bulk of the load burden across the knee joint. That’s why patients with knee osteoarthritis have increased proximal tibial bone mineral density. Dr. Shakoor presented evidence that sustained reduction in dynamic knee loading results in a proportionate reduction in medial tibial bone density over the course of 6 months.

She reported on 51 patients with mild to moderate radiographic and symptomatic medial compartment knee osteoarthritis who were randomized to wear a commercially available flexible mobility shoe or a similar-looking but nonflexible control shoe for 6 hours per day for at least 6 days per week for 6 months. At baseline and again at 6 months, the participants underwent knee bone density measurement and formal gait analysis.

Peak knee adduction moment decreased by 14% over the course of 6 months in the flexible shoe group, significantly greater than the 6% reduction in the controls. Moreover, Dr. Shakoor and her coinvestigators documented a significant reduction in medial tibial bone density in the flexible shoe group. The greater the improvement in knee adduction moment, the larger the reduction in bone density.

In contrast, medial tibial bone density didn’t change significantly in the controls.

Dr. Shakoor said that she had also expected to see a reduction in the ratio of medial to lateral tibial bone density in the flexible shoe group. However, there was no statistically significant change, although there was a trend in that direction.

Asked if reduction in knee adduction moment and/or medial tibial bone density correlated with improved knee pain scores, Dr. Shakoor replied that almost everyone in the study reported improvement in pain, suggesting a placebo effect for that endpoint. In any event, the relatively small study wasn’t powered to evaluate change in pain over time.

The Arthritis Foundation funded the study. Dr. Shakoor is coinventor of the flexible shoe used in the study. The patent, owned by Rush University, has been licensed to Dr. Comfort, which markets the shoe as the Dr. Comfort Flex-OA Mobility Shoe. A percentage of the proceeds from shoe sales is distributed to the university and the coinventors.

[email protected]

LAS VEGAS – Patients with medial compartment knee osteoarthritis who wore a patented flexible mobility shoe experienced a favorable reduction in medial tibial bone mineral density that directly correlated with their improved gait biomechanics and reduced peak knee adduction moment, Najia Shakoor, MD, reported at the World Congress on Osteoarthritis.

“Our results suggest that bone can be modified with sustained load reduction and that evaluation of tibial bone density may be an inexpensive tool for evaluating the consequences of load-reducing interventions,” said Dr. Shakoor, a rheumatologist at Rush University in Chicago.

Indeed, measuring changes in medial tibial bone density over time via serial dual x-ray absorptiometry is an attractive surrogate anatomic marker of a patient’s response to a biomechanical load-reducing intervention such as a special shoe or knee brace, Dr. Shakoor noted at the meeting sponsored by the Osteoarthritis Research Society International.

After all, she added, bone density measurement is simpler than sending a patient to a motion analysis laboratory for multicamera gait analysis using a force plate to evaluate changes in the peak external knee adduction moment (a validated marker of load distribution across the tibial plateau).

Studies suggest that bone, not cartilage, bears the bulk of the load burden across the knee joint. That’s why patients with knee osteoarthritis have increased proximal tibial bone mineral density. Dr. Shakoor presented evidence that sustained reduction in dynamic knee loading results in a proportionate reduction in medial tibial bone density over the course of 6 months.

She reported on 51 patients with mild to moderate radiographic and symptomatic medial compartment knee osteoarthritis who were randomized to wear a commercially available flexible mobility shoe or a similar-looking but nonflexible control shoe for 6 hours per day for at least 6 days per week for 6 months. At baseline and again at 6 months, the participants underwent knee bone density measurement and formal gait analysis.

Peak knee adduction moment decreased by 14% over the course of 6 months in the flexible shoe group, significantly greater than the 6% reduction in the controls. Moreover, Dr. Shakoor and her coinvestigators documented a significant reduction in medial tibial bone density in the flexible shoe group. The greater the improvement in knee adduction moment, the larger the reduction in bone density.

In contrast, medial tibial bone density didn’t change significantly in the controls.

Dr. Shakoor said that she had also expected to see a reduction in the ratio of medial to lateral tibial bone density in the flexible shoe group. However, there was no statistically significant change, although there was a trend in that direction.

Asked if reduction in knee adduction moment and/or medial tibial bone density correlated with improved knee pain scores, Dr. Shakoor replied that almost everyone in the study reported improvement in pain, suggesting a placebo effect for that endpoint. In any event, the relatively small study wasn’t powered to evaluate change in pain over time.

The Arthritis Foundation funded the study. Dr. Shakoor is coinventor of the flexible shoe used in the study. The patent, owned by Rush University, has been licensed to Dr. Comfort, which markets the shoe as the Dr. Comfort Flex-OA Mobility Shoe. A percentage of the proceeds from shoe sales is distributed to the university and the coinventors.

[email protected]