PD-1 blockade should still be considered as a second-line approach in patients with EGFR-mutant non–small-cell lung cancer (NSCLC), as some may still respond to this therapy, investigators reported.

The researchers described a patient who was diagnosed with epidermal growth factor receptor (EGFR)-mutant NSCLC but who also showed high expression of PD-L1.

The 62-year-old woman first presented with a lung nodule and metastasis in the right hip, which were EGFR-mutant and had a PD-L1 tumor proportion score of 90%. She was treated with erlotinib – an EGFR tyrosine kinase inhibitor – and radiotherapy, according to the report, published in Annals of Oncology.

Two months later, she developed multiple new metastases in the chest wall. These also showed high PD-L1 expression, but no EGFR mutations, so she was treated with pembrolizumab as second-line therapy.

After the first course of treatment with pembrolizumab, the hip pain improved dramatically, and after three cycles the primary and metastatic lesions disappeared completely.

“Immunofluorescent analysis of both right ilium and chest wall lesions with an anti-EGFR antibody specific to Ex.19 del and an anti-PD-L1 antibody revealed the presence of distinct heterogeneity of EGFR-mutant clones and PD-L1 highly-expressing clones,” wrote Kei Kunimasa, MD, of Osaka International Cancer Institute, and coauthors.

Current clinical trials suggested that patients with EGFR mutations are likely to have a poor response to PD-1 blockade therapies for NSCLC, and the authors agreed that patients with EGFR mutations should be treated with EGFR tyrosine kinase inhibitors as first-line therapy.

“However, the present case suggested that shorter PFS in EGFR-TKI treatment for EGFR-mutant NSCLC patients with high PD-L1 TPS and without acquired T790M mutation could encourage us to try PD-1 blockade therapy as second line therapy,” they wrote.

The investigators suggested that certain clinical factors could identify patients with EGFR-mutant NSCLC who might respond well to PD-1 blockade, such as progression-free survival on EGFR tyrosine kinase inhibitor treatment, other targetable resistant mutations, tumor mutation burden, and PD-L1 expression.

Two authors reported grants and personal fees from pharmaceutical companies outside the submitted work. No other conflicts of interest were declared.

SOURCE: Kunimasa K et al. Ann Oncol, 2018 Aug 7. doi: 10.1093/annonc/mdy312.

PD-1 blockade should still be considered as a second-line approach in patients with EGFR-mutant non–small-cell lung cancer (NSCLC), as some may still respond to this therapy, investigators reported.

The researchers described a patient who was diagnosed with epidermal growth factor receptor (EGFR)-mutant NSCLC but who also showed high expression of PD-L1.

The 62-year-old woman first presented with a lung nodule and metastasis in the right hip, which were EGFR-mutant and had a PD-L1 tumor proportion score of 90%. She was treated with erlotinib – an EGFR tyrosine kinase inhibitor – and radiotherapy, according to the report, published in Annals of Oncology.

Two months later, she developed multiple new metastases in the chest wall. These also showed high PD-L1 expression, but no EGFR mutations, so she was treated with pembrolizumab as second-line therapy.

After the first course of treatment with pembrolizumab, the hip pain improved dramatically, and after three cycles the primary and metastatic lesions disappeared completely.

“Immunofluorescent analysis of both right ilium and chest wall lesions with an anti-EGFR antibody specific to Ex.19 del and an anti-PD-L1 antibody revealed the presence of distinct heterogeneity of EGFR-mutant clones and PD-L1 highly-expressing clones,” wrote Kei Kunimasa, MD, of Osaka International Cancer Institute, and coauthors.

Current clinical trials suggested that patients with EGFR mutations are likely to have a poor response to PD-1 blockade therapies for NSCLC, and the authors agreed that patients with EGFR mutations should be treated with EGFR tyrosine kinase inhibitors as first-line therapy.

“However, the present case suggested that shorter PFS in EGFR-TKI treatment for EGFR-mutant NSCLC patients with high PD-L1 TPS and without acquired T790M mutation could encourage us to try PD-1 blockade therapy as second line therapy,” they wrote.

The investigators suggested that certain clinical factors could identify patients with EGFR-mutant NSCLC who might respond well to PD-1 blockade, such as progression-free survival on EGFR tyrosine kinase inhibitor treatment, other targetable resistant mutations, tumor mutation burden, and PD-L1 expression.

Two authors reported grants and personal fees from pharmaceutical companies outside the submitted work. No other conflicts of interest were declared.

SOURCE: Kunimasa K et al. Ann Oncol, 2018 Aug 7. doi: 10.1093/annonc/mdy312.

PD-1 blockade should still be considered as a second-line approach in patients with EGFR-mutant non–small-cell lung cancer (NSCLC), as some may still respond to this therapy, investigators reported.

The researchers described a patient who was diagnosed with epidermal growth factor receptor (EGFR)-mutant NSCLC but who also showed high expression of PD-L1.

The 62-year-old woman first presented with a lung nodule and metastasis in the right hip, which were EGFR-mutant and had a PD-L1 tumor proportion score of 90%. She was treated with erlotinib – an EGFR tyrosine kinase inhibitor – and radiotherapy, according to the report, published in Annals of Oncology.

Two months later, she developed multiple new metastases in the chest wall. These also showed high PD-L1 expression, but no EGFR mutations, so she was treated with pembrolizumab as second-line therapy.

After the first course of treatment with pembrolizumab, the hip pain improved dramatically, and after three cycles the primary and metastatic lesions disappeared completely.

“Immunofluorescent analysis of both right ilium and chest wall lesions with an anti-EGFR antibody specific to Ex.19 del and an anti-PD-L1 antibody revealed the presence of distinct heterogeneity of EGFR-mutant clones and PD-L1 highly-expressing clones,” wrote Kei Kunimasa, MD, of Osaka International Cancer Institute, and coauthors.

Current clinical trials suggested that patients with EGFR mutations are likely to have a poor response to PD-1 blockade therapies for NSCLC, and the authors agreed that patients with EGFR mutations should be treated with EGFR tyrosine kinase inhibitors as first-line therapy.

“However, the present case suggested that shorter PFS in EGFR-TKI treatment for EGFR-mutant NSCLC patients with high PD-L1 TPS and without acquired T790M mutation could encourage us to try PD-1 blockade therapy as second line therapy,” they wrote.

The investigators suggested that certain clinical factors could identify patients with EGFR-mutant NSCLC who might respond well to PD-1 blockade, such as progression-free survival on EGFR tyrosine kinase inhibitor treatment, other targetable resistant mutations, tumor mutation burden, and PD-L1 expression.

Two authors reported grants and personal fees from pharmaceutical companies outside the submitted work. No other conflicts of interest were declared.

SOURCE: Kunimasa K et al. Ann Oncol, 2018 Aug 7. doi: 10.1093/annonc/mdy312.

CHICAGO – For patients with gastrointestinal stromal tumor (GIST) with KIT mutations conferring resistance to imatinib, a strategy of rapid alteration of drugs with complementary activity against KIT mutations is feasible but has thus far failed to yield significant clinical benefits, investigators said.

There were no objective responses among 12 patients treated continuously with 3 days of sunitinib (Sutent) followed by 4 days of regorafenib (Stivarga), and although 4 patients had stable disease in the short term, in each case the disease progressed within 16 weeks, reported Cesar Serrano-Garcia, MD, from the Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, and his colleagues.

“Drug exposure is critical to effectively target specific resistant subpopulations and low exposure may have contributed to the lack of efficacy in this cohort,” they wrote in a poster presented at the annual meeting of the American Society of Clinical Oncology.

The investigators noted that the main mechanism of resistance to imatinib (Gleevec) in GIST is polyclonal emergence of KIT secondary mutations. They then theorized that rapid alteration of sunitinib with regorafenib, which both have complementary activity against different KIT resistance mutations, could be a novel therapeutic strategy for controlling imatinib-resistant disease.

Both agents are active against KIT and platelet-derived growth factor receptor alpha (PDGFR-alpha). Sunitinib has stronger activity against ATP-binding pocket mutations, and regorafenib is more effective against activation loop oncoproteins, the investigators explained.

They conducted a phase Ib trial to evaluate the safety and preliminary efficacy of the strategy in patients with metastatic GIST that had advanced on therapy with all established protocols. The trial had a standard 3+3 design to determine the recommended phase 2 dose; a total of 14 patients were enrolled, but only 12 received one or more complete cycles.

The median patient age was 63.5%. Nine patients had Eastern Cooperative Oncology Group performance status of 0, and five had an ECOG status of 1. The patients had received a median of four prior lines of therapy, and all had received at least three lines.

The primary mutations were at KIT exon 11 in eight patients, exon 9 in five patients, and a KIT/PDGFR-alpha wild type in one patient.

Of the 12 patients who received one or more complete cycles, 7 were treated with sunitinib 37.5 mg daily for 3 days, followed by regorafenib 120 mg daily for 4 days. There were no dose-limiting toxicities in this group. The median number of cycles delivered was 2 (range 1-4).

The other five patients were treated with sunitinib at the same 37.5 mg daily dose for 3 days, followed immediately by regorafenib 160 mg daily for 4 days. There were two dose-limiting toxicities in this group, both grade 3 hypophosphatemia, one of which was refractory to phosphorous replacement.

Antitumor activity according to Response Evaluation Criteria in Solid Tumors version 1.1 included four cases of stable disease at the time of the efficacy analysis, and eight cases of disease progression. The median progression-free survival was 1.9 months. As noted before, there were no complete or partial responses among the 12 patients.

A pharmacokinetic profile at cycle 1 showed that neither drug reached its reported active blood drug levels.

The patients appeared to tolerate the treatment well, with grade 1 or 2 fatigue in all patients being the most common adverse events. Grade 3 or 4 events included hand-foot syndrome, hypertension, and hypophosphatemia in two patients each.

As noted, the authors acknowledged that low drug exposure levels may explain the lack of any responses in this cohort.

“Therapeutic strategies based on KIT inhibition remain crucial in GIST patients progressing to multiple lines,” they wrote.

The study was supported by an ASCO Young Investigator Award, Pfizer, and Bayer. Dr. Serrano-Garcia disclosed honoraria from Bayer, a consulting or advisory role for Deciphera, research funding from Bayer and Deciphera, and travel accommodations and expenses from Pfizer.

SOURCE: Serrano-Garcia C et al. ASCO 2018, Abstract 11510.

CHICAGO – For patients with gastrointestinal stromal tumor (GIST) with KIT mutations conferring resistance to imatinib, a strategy of rapid alteration of drugs with complementary activity against KIT mutations is feasible but has thus far failed to yield significant clinical benefits, investigators said.

There were no objective responses among 12 patients treated continuously with 3 days of sunitinib (Sutent) followed by 4 days of regorafenib (Stivarga), and although 4 patients had stable disease in the short term, in each case the disease progressed within 16 weeks, reported Cesar Serrano-Garcia, MD, from the Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, and his colleagues.

“Drug exposure is critical to effectively target specific resistant subpopulations and low exposure may have contributed to the lack of efficacy in this cohort,” they wrote in a poster presented at the annual meeting of the American Society of Clinical Oncology.

The investigators noted that the main mechanism of resistance to imatinib (Gleevec) in GIST is polyclonal emergence of KIT secondary mutations. They then theorized that rapid alteration of sunitinib with regorafenib, which both have complementary activity against different KIT resistance mutations, could be a novel therapeutic strategy for controlling imatinib-resistant disease.

Both agents are active against KIT and platelet-derived growth factor receptor alpha (PDGFR-alpha). Sunitinib has stronger activity against ATP-binding pocket mutations, and regorafenib is more effective against activation loop oncoproteins, the investigators explained.

They conducted a phase Ib trial to evaluate the safety and preliminary efficacy of the strategy in patients with metastatic GIST that had advanced on therapy with all established protocols. The trial had a standard 3+3 design to determine the recommended phase 2 dose; a total of 14 patients were enrolled, but only 12 received one or more complete cycles.

The median patient age was 63.5%. Nine patients had Eastern Cooperative Oncology Group performance status of 0, and five had an ECOG status of 1. The patients had received a median of four prior lines of therapy, and all had received at least three lines.

The primary mutations were at KIT exon 11 in eight patients, exon 9 in five patients, and a KIT/PDGFR-alpha wild type in one patient.

Of the 12 patients who received one or more complete cycles, 7 were treated with sunitinib 37.5 mg daily for 3 days, followed by regorafenib 120 mg daily for 4 days. There were no dose-limiting toxicities in this group. The median number of cycles delivered was 2 (range 1-4).

The other five patients were treated with sunitinib at the same 37.5 mg daily dose for 3 days, followed immediately by regorafenib 160 mg daily for 4 days. There were two dose-limiting toxicities in this group, both grade 3 hypophosphatemia, one of which was refractory to phosphorous replacement.

Antitumor activity according to Response Evaluation Criteria in Solid Tumors version 1.1 included four cases of stable disease at the time of the efficacy analysis, and eight cases of disease progression. The median progression-free survival was 1.9 months. As noted before, there were no complete or partial responses among the 12 patients.

A pharmacokinetic profile at cycle 1 showed that neither drug reached its reported active blood drug levels.

The patients appeared to tolerate the treatment well, with grade 1 or 2 fatigue in all patients being the most common adverse events. Grade 3 or 4 events included hand-foot syndrome, hypertension, and hypophosphatemia in two patients each.

As noted, the authors acknowledged that low drug exposure levels may explain the lack of any responses in this cohort.

“Therapeutic strategies based on KIT inhibition remain crucial in GIST patients progressing to multiple lines,” they wrote.

The study was supported by an ASCO Young Investigator Award, Pfizer, and Bayer. Dr. Serrano-Garcia disclosed honoraria from Bayer, a consulting or advisory role for Deciphera, research funding from Bayer and Deciphera, and travel accommodations and expenses from Pfizer.

SOURCE: Serrano-Garcia C et al. ASCO 2018, Abstract 11510.

CHICAGO – For patients with gastrointestinal stromal tumor (GIST) with KIT mutations conferring resistance to imatinib, a strategy of rapid alteration of drugs with complementary activity against KIT mutations is feasible but has thus far failed to yield significant clinical benefits, investigators said.

There were no objective responses among 12 patients treated continuously with 3 days of sunitinib (Sutent) followed by 4 days of regorafenib (Stivarga), and although 4 patients had stable disease in the short term, in each case the disease progressed within 16 weeks, reported Cesar Serrano-Garcia, MD, from the Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, and his colleagues.

“Drug exposure is critical to effectively target specific resistant subpopulations and low exposure may have contributed to the lack of efficacy in this cohort,” they wrote in a poster presented at the annual meeting of the American Society of Clinical Oncology.

The investigators noted that the main mechanism of resistance to imatinib (Gleevec) in GIST is polyclonal emergence of KIT secondary mutations. They then theorized that rapid alteration of sunitinib with regorafenib, which both have complementary activity against different KIT resistance mutations, could be a novel therapeutic strategy for controlling imatinib-resistant disease.

Both agents are active against KIT and platelet-derived growth factor receptor alpha (PDGFR-alpha). Sunitinib has stronger activity against ATP-binding pocket mutations, and regorafenib is more effective against activation loop oncoproteins, the investigators explained.

They conducted a phase Ib trial to evaluate the safety and preliminary efficacy of the strategy in patients with metastatic GIST that had advanced on therapy with all established protocols. The trial had a standard 3+3 design to determine the recommended phase 2 dose; a total of 14 patients were enrolled, but only 12 received one or more complete cycles.

The median patient age was 63.5%. Nine patients had Eastern Cooperative Oncology Group performance status of 0, and five had an ECOG status of 1. The patients had received a median of four prior lines of therapy, and all had received at least three lines.

The primary mutations were at KIT exon 11 in eight patients, exon 9 in five patients, and a KIT/PDGFR-alpha wild type in one patient.

Of the 12 patients who received one or more complete cycles, 7 were treated with sunitinib 37.5 mg daily for 3 days, followed by regorafenib 120 mg daily for 4 days. There were no dose-limiting toxicities in this group. The median number of cycles delivered was 2 (range 1-4).

The other five patients were treated with sunitinib at the same 37.5 mg daily dose for 3 days, followed immediately by regorafenib 160 mg daily for 4 days. There were two dose-limiting toxicities in this group, both grade 3 hypophosphatemia, one of which was refractory to phosphorous replacement.

Antitumor activity according to Response Evaluation Criteria in Solid Tumors version 1.1 included four cases of stable disease at the time of the efficacy analysis, and eight cases of disease progression. The median progression-free survival was 1.9 months. As noted before, there were no complete or partial responses among the 12 patients.

A pharmacokinetic profile at cycle 1 showed that neither drug reached its reported active blood drug levels.

The patients appeared to tolerate the treatment well, with grade 1 or 2 fatigue in all patients being the most common adverse events. Grade 3 or 4 events included hand-foot syndrome, hypertension, and hypophosphatemia in two patients each.

As noted, the authors acknowledged that low drug exposure levels may explain the lack of any responses in this cohort.

“Therapeutic strategies based on KIT inhibition remain crucial in GIST patients progressing to multiple lines,” they wrote.

The study was supported by an ASCO Young Investigator Award, Pfizer, and Bayer. Dr. Serrano-Garcia disclosed honoraria from Bayer, a consulting or advisory role for Deciphera, research funding from Bayer and Deciphera, and travel accommodations and expenses from Pfizer.

SOURCE: Serrano-Garcia C et al. ASCO 2018, Abstract 11510.

CHICAGO – Detection of circulating tumor DNA (ctDNA), aka “liquid biopsy,” may serve as a noninvasive marker for disease heterogeneity and aid in the assessment of clinical responses to therapy for patients with gastrointestinal stromal tumors (GIST), according to investigators.

In a phase 1 trial of the investigational agent DCC-2618, a pan-KIT/platelet-derived growth factor receptor alpha (PDGFRA) switch control inhibitor, identification of ctDNA by next-generation sequencing (NGS) was accomplished in the majority of patients, with findings that support the need for a broad-spectrum KIT inhibitor for patients with GIST resistant to imatinib (Gleevec), reported Suzanne George, MD, of Dana-Farber Cancer Institute in Boston, and her colleagues.

“This data demonstrates for the first time that the distribution of resistance mutations in KIT across exons 13, 14, 17, and 18 or a combination thereof is similar in 2nd, 3rd, and 4th-line patients,” they wrote in a poster presented at the annual meeting of the American Society of Clinical Oncology.

The dose-finding and escalation trial included baseline evaluations of KIT/PDGFRA mutations with both ctDNA and fresh tumor biopsy, and ctDNA measurements during treatment.

Biopsy detected 68 KIT mutations at baseline in 81 patients, and ctDNA detected 75 mutations in 95 patients. Some patients had multiple mutations within one exon.

An analysis of mutations by response showed that of 73 patients with detectable KIT mutations by ctDNA at baseline, 35 became KIT ctDNA negative during at least one treatment time point. Of this group, 8 had a partial response (PR) and 27 had stable disease (SD). In all, 57 of the 73 patients had a more than 50% reduction in KIT mutation allele frequency (MAF).

Some patients with stable disease remained KIT negative out to 60 weeks following the first DCC-2618 dose.

The investigators also looked at ctDNA at baseline (21 patients) and post treatment (20 patients) in those who had a PR as their best response. Ten of these patients had KIT mutations detected at baseline, and of this group, eight became KIT negative after treatment; one had no detectable mutations in one exon and one exon with an MAF less than .1%. No posttreatment samples were available for the remaining patient.

There were preliminary data suggesting that DCC-2618 in the second line could be more efficacious than sunitinib (Sutent) in the same setting, and that in KIT-driven GIST DCC-2618 may provide more benefit in the second line compared with the fourth or subsequent lines of therapy, the authors stated.

“The mutational profile of KIT in tumors and plasma at baseline in GIST patients supports the need for a broad spectrum KIT inhibitor in all post-imatinib lines of therapy,” they wrote.

The trial is supported by Deciphera Pharmaceuticals. Dr. George disclosed stock or other ownership in Abbott Laboratories and Abbvie, consulting/advising for AstraZeneca, Blueprint Medicines, and Deciphera, and institutional research funding from Ariad, Bayer, Blueprint Medicine, Deciphera, Novartis, and Pfizer.

SOURCE: George S et al. ASCO 2018. Abstract 11511.

CHICAGO – Detection of circulating tumor DNA (ctDNA), aka “liquid biopsy,” may serve as a noninvasive marker for disease heterogeneity and aid in the assessment of clinical responses to therapy for patients with gastrointestinal stromal tumors (GIST), according to investigators.

In a phase 1 trial of the investigational agent DCC-2618, a pan-KIT/platelet-derived growth factor receptor alpha (PDGFRA) switch control inhibitor, identification of ctDNA by next-generation sequencing (NGS) was accomplished in the majority of patients, with findings that support the need for a broad-spectrum KIT inhibitor for patients with GIST resistant to imatinib (Gleevec), reported Suzanne George, MD, of Dana-Farber Cancer Institute in Boston, and her colleagues.

“This data demonstrates for the first time that the distribution of resistance mutations in KIT across exons 13, 14, 17, and 18 or a combination thereof is similar in 2nd, 3rd, and 4th-line patients,” they wrote in a poster presented at the annual meeting of the American Society of Clinical Oncology.

The dose-finding and escalation trial included baseline evaluations of KIT/PDGFRA mutations with both ctDNA and fresh tumor biopsy, and ctDNA measurements during treatment.

Biopsy detected 68 KIT mutations at baseline in 81 patients, and ctDNA detected 75 mutations in 95 patients. Some patients had multiple mutations within one exon.

An analysis of mutations by response showed that of 73 patients with detectable KIT mutations by ctDNA at baseline, 35 became KIT ctDNA negative during at least one treatment time point. Of this group, 8 had a partial response (PR) and 27 had stable disease (SD). In all, 57 of the 73 patients had a more than 50% reduction in KIT mutation allele frequency (MAF).

Some patients with stable disease remained KIT negative out to 60 weeks following the first DCC-2618 dose.

The investigators also looked at ctDNA at baseline (21 patients) and post treatment (20 patients) in those who had a PR as their best response. Ten of these patients had KIT mutations detected at baseline, and of this group, eight became KIT negative after treatment; one had no detectable mutations in one exon and one exon with an MAF less than .1%. No posttreatment samples were available for the remaining patient.

There were preliminary data suggesting that DCC-2618 in the second line could be more efficacious than sunitinib (Sutent) in the same setting, and that in KIT-driven GIST DCC-2618 may provide more benefit in the second line compared with the fourth or subsequent lines of therapy, the authors stated.

“The mutational profile of KIT in tumors and plasma at baseline in GIST patients supports the need for a broad spectrum KIT inhibitor in all post-imatinib lines of therapy,” they wrote.

The trial is supported by Deciphera Pharmaceuticals. Dr. George disclosed stock or other ownership in Abbott Laboratories and Abbvie, consulting/advising for AstraZeneca, Blueprint Medicines, and Deciphera, and institutional research funding from Ariad, Bayer, Blueprint Medicine, Deciphera, Novartis, and Pfizer.

SOURCE: George S et al. ASCO 2018. Abstract 11511.

CHICAGO – Detection of circulating tumor DNA (ctDNA), aka “liquid biopsy,” may serve as a noninvasive marker for disease heterogeneity and aid in the assessment of clinical responses to therapy for patients with gastrointestinal stromal tumors (GIST), according to investigators.

In a phase 1 trial of the investigational agent DCC-2618, a pan-KIT/platelet-derived growth factor receptor alpha (PDGFRA) switch control inhibitor, identification of ctDNA by next-generation sequencing (NGS) was accomplished in the majority of patients, with findings that support the need for a broad-spectrum KIT inhibitor for patients with GIST resistant to imatinib (Gleevec), reported Suzanne George, MD, of Dana-Farber Cancer Institute in Boston, and her colleagues.

“This data demonstrates for the first time that the distribution of resistance mutations in KIT across exons 13, 14, 17, and 18 or a combination thereof is similar in 2nd, 3rd, and 4th-line patients,” they wrote in a poster presented at the annual meeting of the American Society of Clinical Oncology.

The dose-finding and escalation trial included baseline evaluations of KIT/PDGFRA mutations with both ctDNA and fresh tumor biopsy, and ctDNA measurements during treatment.

Biopsy detected 68 KIT mutations at baseline in 81 patients, and ctDNA detected 75 mutations in 95 patients. Some patients had multiple mutations within one exon.

An analysis of mutations by response showed that of 73 patients with detectable KIT mutations by ctDNA at baseline, 35 became KIT ctDNA negative during at least one treatment time point. Of this group, 8 had a partial response (PR) and 27 had stable disease (SD). In all, 57 of the 73 patients had a more than 50% reduction in KIT mutation allele frequency (MAF).

Some patients with stable disease remained KIT negative out to 60 weeks following the first DCC-2618 dose.

The investigators also looked at ctDNA at baseline (21 patients) and post treatment (20 patients) in those who had a PR as their best response. Ten of these patients had KIT mutations detected at baseline, and of this group, eight became KIT negative after treatment; one had no detectable mutations in one exon and one exon with an MAF less than .1%. No posttreatment samples were available for the remaining patient.

There were preliminary data suggesting that DCC-2618 in the second line could be more efficacious than sunitinib (Sutent) in the same setting, and that in KIT-driven GIST DCC-2618 may provide more benefit in the second line compared with the fourth or subsequent lines of therapy, the authors stated.

“The mutational profile of KIT in tumors and plasma at baseline in GIST patients supports the need for a broad spectrum KIT inhibitor in all post-imatinib lines of therapy,” they wrote.

The trial is supported by Deciphera Pharmaceuticals. Dr. George disclosed stock or other ownership in Abbott Laboratories and Abbvie, consulting/advising for AstraZeneca, Blueprint Medicines, and Deciphera, and institutional research funding from Ariad, Bayer, Blueprint Medicine, Deciphera, Novartis, and Pfizer.

SOURCE: George S et al. ASCO 2018. Abstract 11511.

Click here to view the articles published in August 2018.

Click here to view the articles published in August 2018.

Click here to view the articles published in August 2018.

MIAMI—For patients with Parkinson’s disease, a regime of transcranial magnetic stimulation (TMS) and aerobic exercise results in motor improvements that are sustained for one month, according to a study presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. Another study by the same researchers indicates that stimulation of two regions in the premotor associative cortex, compared with stimulation of one region, improves axial symptoms in Parkinson’s disease. Both studies suggest that TMS prolongs the cortical silent period.

TMS Prolonged Cortical Silent Period

Aerobic exercise improves the motor symptoms of Parkinson’s disease. A proposed mechanism for this improvement is the enhancement of brain-derived neurotrophic factor (BDNF) signaling or activity. TMS also improves motor symptoms of Parkinson’s disease, and rat studies indicate that it enhances BDNF-tropomyosin receptor kinase B (TrkB) signaling, which is a biomarker of plasticity.

Milton C. Biagioni, MD, Assistant Professor of Neurology at the Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at NYU Langone Health in New York, and colleagues studied differences in BDNF-TrkB signaling between 16 patients with Parkinson’s disease and five healthy controls. Levels of all TrkB signaling biomarkers were significantly higher in healthy controls than in patients with Parkinson’s disease.

Dr. Biagioni and colleagues also investigated the biologic effects, motor outcomes, and physiologic outcomes of repetitive TMS and aerobic exercise in patients with Parkinson’s disease in a randomized, double-blind trial. In this trial, 16 patients with Parkinson’s disease participated in daily 40-minute sessions of aerobic exercise. Participants were randomized 1:1 to receive high-frequency repetitive TMS or sham stimulation over the motor cortex. Patients exercised on a recumbent linear cross trainer.

Motor outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) and Timed Up and Go (TUG) test. Neurophysiologic outcomes included the cortical silent period, motor threshold, and paired-associative stimulation (PAS-25). The researchers obtained peripheral blood lymphocytes from participants in the morning to measure BDNF activity. Outcomes were measured at baseline, two weeks after the intervention, and one month after the intervention.

Among patients with Parkinson’s disease, mean age was about 65. Mean disease duration was eight years, and mean UPDRS III score was 46.4. The researchers found no significant differences at baseline between patients randomized to TMS and those randomized to sham.

BDNF-TrkB signaling increased by 29.3% in the sham group and by 36.6% in the TMS group. Both increases were statistically significant, but the difference between groups was not significant. At one month, the cortical silent period was significantly prolonged after TMS, compared with sham. All patients had significant improvement in UPDRS III. Improvements in UPDRS III and TUG were sustained for one month in the TMS group.

Multifocal Stimulation Improved Axial Score

A previous study indicated that low-frequency repetitive TMS over the supplementary motor area (SMA) effectively improves motor symptoms in Parkinson’s disease. Like the SMA, the dorsal premotor cortex (PMd) is involved in motor planning and motor control. Researchers had not previously studied multifocal TMS over both targets, and Dr. Biagioni and colleagues decided to examine this technique.

They conducted a parallel, active-controlled, double-blind, randomized study of four weekly sessions of low-frequency repetitive TMS in 22 patients with Parkinson’s disease. The control group received TMS over the SMA and sham stimulation over the PMd. The experimental group received TMS over both areas. The study outcomes included all components of the UPDRS, as well as UPDRS III axial, tremor, rigidity, and bradykinesia scores. Dr. Biagioni and colleagues assessed patients in the on state at baseline and at four weeks after treatment.

Participants’ mean age was 65, and eight patients were female. Mean disease duration was approximately nine years, mean UPDRS total score was 53.1, and mean UPDRS III score was 35.9. The only significant difference between the control and experimental groups at baseline was Montreal Cognitive Assessment score, which was 24.2 in the control group and 26.4 in the experimental group.

Both interventions were well tolerated. After one month, UPDRS III decreased by 5.5 points in the control group and by 6.5 points in the experimental group. Both changes were statistically significant, but the difference between groups was not significant. The researchers found no difference between groups in total UPDRS and UPDRS III after one month. Axial score significantly decreased in the experimental group, compared with the control group, but the researchers found no significant differences between groups in rigidity, tremor, or bradykinesia scores. In addition, the cortical silent period was significantly prolonged in the experimental group, compared with the control group.

—Erik Greb

Suggested Reading

Chou YH, Hickey PT, Sundman M, et al. Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis. JAMA Neurol. 2015;72(4):432-440.

Shirota Y, Ohtsu H, Hamada M, et al. Supplementary motor area stimulation for Parkinson disease: a randomized controlled study. Neurology. 2013;80(15):1400-1405.

MIAMI—For patients with Parkinson’s disease, a regime of transcranial magnetic stimulation (TMS) and aerobic exercise results in motor improvements that are sustained for one month, according to a study presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. Another study by the same researchers indicates that stimulation of two regions in the premotor associative cortex, compared with stimulation of one region, improves axial symptoms in Parkinson’s disease. Both studies suggest that TMS prolongs the cortical silent period.

TMS Prolonged Cortical Silent Period

Aerobic exercise improves the motor symptoms of Parkinson’s disease. A proposed mechanism for this improvement is the enhancement of brain-derived neurotrophic factor (BDNF) signaling or activity. TMS also improves motor symptoms of Parkinson’s disease, and rat studies indicate that it enhances BDNF-tropomyosin receptor kinase B (TrkB) signaling, which is a biomarker of plasticity.

Milton C. Biagioni, MD, Assistant Professor of Neurology at the Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at NYU Langone Health in New York, and colleagues studied differences in BDNF-TrkB signaling between 16 patients with Parkinson’s disease and five healthy controls. Levels of all TrkB signaling biomarkers were significantly higher in healthy controls than in patients with Parkinson’s disease.

Dr. Biagioni and colleagues also investigated the biologic effects, motor outcomes, and physiologic outcomes of repetitive TMS and aerobic exercise in patients with Parkinson’s disease in a randomized, double-blind trial. In this trial, 16 patients with Parkinson’s disease participated in daily 40-minute sessions of aerobic exercise. Participants were randomized 1:1 to receive high-frequency repetitive TMS or sham stimulation over the motor cortex. Patients exercised on a recumbent linear cross trainer.

Motor outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) and Timed Up and Go (TUG) test. Neurophysiologic outcomes included the cortical silent period, motor threshold, and paired-associative stimulation (PAS-25). The researchers obtained peripheral blood lymphocytes from participants in the morning to measure BDNF activity. Outcomes were measured at baseline, two weeks after the intervention, and one month after the intervention.

Among patients with Parkinson’s disease, mean age was about 65. Mean disease duration was eight years, and mean UPDRS III score was 46.4. The researchers found no significant differences at baseline between patients randomized to TMS and those randomized to sham.

BDNF-TrkB signaling increased by 29.3% in the sham group and by 36.6% in the TMS group. Both increases were statistically significant, but the difference between groups was not significant. At one month, the cortical silent period was significantly prolonged after TMS, compared with sham. All patients had significant improvement in UPDRS III. Improvements in UPDRS III and TUG were sustained for one month in the TMS group.

Multifocal Stimulation Improved Axial Score

A previous study indicated that low-frequency repetitive TMS over the supplementary motor area (SMA) effectively improves motor symptoms in Parkinson’s disease. Like the SMA, the dorsal premotor cortex (PMd) is involved in motor planning and motor control. Researchers had not previously studied multifocal TMS over both targets, and Dr. Biagioni and colleagues decided to examine this technique.

They conducted a parallel, active-controlled, double-blind, randomized study of four weekly sessions of low-frequency repetitive TMS in 22 patients with Parkinson’s disease. The control group received TMS over the SMA and sham stimulation over the PMd. The experimental group received TMS over both areas. The study outcomes included all components of the UPDRS, as well as UPDRS III axial, tremor, rigidity, and bradykinesia scores. Dr. Biagioni and colleagues assessed patients in the on state at baseline and at four weeks after treatment.

Participants’ mean age was 65, and eight patients were female. Mean disease duration was approximately nine years, mean UPDRS total score was 53.1, and mean UPDRS III score was 35.9. The only significant difference between the control and experimental groups at baseline was Montreal Cognitive Assessment score, which was 24.2 in the control group and 26.4 in the experimental group.

Both interventions were well tolerated. After one month, UPDRS III decreased by 5.5 points in the control group and by 6.5 points in the experimental group. Both changes were statistically significant, but the difference between groups was not significant. The researchers found no difference between groups in total UPDRS and UPDRS III after one month. Axial score significantly decreased in the experimental group, compared with the control group, but the researchers found no significant differences between groups in rigidity, tremor, or bradykinesia scores. In addition, the cortical silent period was significantly prolonged in the experimental group, compared with the control group.

—Erik Greb

Suggested Reading

Chou YH, Hickey PT, Sundman M, et al. Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis. JAMA Neurol. 2015;72(4):432-440.

Shirota Y, Ohtsu H, Hamada M, et al. Supplementary motor area stimulation for Parkinson disease: a randomized controlled study. Neurology. 2013;80(15):1400-1405.

MIAMI—For patients with Parkinson’s disease, a regime of transcranial magnetic stimulation (TMS) and aerobic exercise results in motor improvements that are sustained for one month, according to a study presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. Another study by the same researchers indicates that stimulation of two regions in the premotor associative cortex, compared with stimulation of one region, improves axial symptoms in Parkinson’s disease. Both studies suggest that TMS prolongs the cortical silent period.

TMS Prolonged Cortical Silent Period

Aerobic exercise improves the motor symptoms of Parkinson’s disease. A proposed mechanism for this improvement is the enhancement of brain-derived neurotrophic factor (BDNF) signaling or activity. TMS also improves motor symptoms of Parkinson’s disease, and rat studies indicate that it enhances BDNF-tropomyosin receptor kinase B (TrkB) signaling, which is a biomarker of plasticity.

Milton C. Biagioni, MD, Assistant Professor of Neurology at the Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at NYU Langone Health in New York, and colleagues studied differences in BDNF-TrkB signaling between 16 patients with Parkinson’s disease and five healthy controls. Levels of all TrkB signaling biomarkers were significantly higher in healthy controls than in patients with Parkinson’s disease.

Dr. Biagioni and colleagues also investigated the biologic effects, motor outcomes, and physiologic outcomes of repetitive TMS and aerobic exercise in patients with Parkinson’s disease in a randomized, double-blind trial. In this trial, 16 patients with Parkinson’s disease participated in daily 40-minute sessions of aerobic exercise. Participants were randomized 1:1 to receive high-frequency repetitive TMS or sham stimulation over the motor cortex. Patients exercised on a recumbent linear cross trainer.

Motor outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) and Timed Up and Go (TUG) test. Neurophysiologic outcomes included the cortical silent period, motor threshold, and paired-associative stimulation (PAS-25). The researchers obtained peripheral blood lymphocytes from participants in the morning to measure BDNF activity. Outcomes were measured at baseline, two weeks after the intervention, and one month after the intervention.

Among patients with Parkinson’s disease, mean age was about 65. Mean disease duration was eight years, and mean UPDRS III score was 46.4. The researchers found no significant differences at baseline between patients randomized to TMS and those randomized to sham.

BDNF-TrkB signaling increased by 29.3% in the sham group and by 36.6% in the TMS group. Both increases were statistically significant, but the difference between groups was not significant. At one month, the cortical silent period was significantly prolonged after TMS, compared with sham. All patients had significant improvement in UPDRS III. Improvements in UPDRS III and TUG were sustained for one month in the TMS group.

Multifocal Stimulation Improved Axial Score

A previous study indicated that low-frequency repetitive TMS over the supplementary motor area (SMA) effectively improves motor symptoms in Parkinson’s disease. Like the SMA, the dorsal premotor cortex (PMd) is involved in motor planning and motor control. Researchers had not previously studied multifocal TMS over both targets, and Dr. Biagioni and colleagues decided to examine this technique.

They conducted a parallel, active-controlled, double-blind, randomized study of four weekly sessions of low-frequency repetitive TMS in 22 patients with Parkinson’s disease. The control group received TMS over the SMA and sham stimulation over the PMd. The experimental group received TMS over both areas. The study outcomes included all components of the UPDRS, as well as UPDRS III axial, tremor, rigidity, and bradykinesia scores. Dr. Biagioni and colleagues assessed patients in the on state at baseline and at four weeks after treatment.

Participants’ mean age was 65, and eight patients were female. Mean disease duration was approximately nine years, mean UPDRS total score was 53.1, and mean UPDRS III score was 35.9. The only significant difference between the control and experimental groups at baseline was Montreal Cognitive Assessment score, which was 24.2 in the control group and 26.4 in the experimental group.

Both interventions were well tolerated. After one month, UPDRS III decreased by 5.5 points in the control group and by 6.5 points in the experimental group. Both changes were statistically significant, but the difference between groups was not significant. The researchers found no difference between groups in total UPDRS and UPDRS III after one month. Axial score significantly decreased in the experimental group, compared with the control group, but the researchers found no significant differences between groups in rigidity, tremor, or bradykinesia scores. In addition, the cortical silent period was significantly prolonged in the experimental group, compared with the control group.

—Erik Greb

Suggested Reading

Chou YH, Hickey PT, Sundman M, et al. Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis. JAMA Neurol. 2015;72(4):432-440.

Shirota Y, Ohtsu H, Hamada M, et al. Supplementary motor area stimulation for Parkinson disease: a randomized controlled study. Neurology. 2013;80(15):1400-1405.

“Follow your passion” has long been a self-help mantra when it comes to a career. The idea has been that doing what you love will provide the fuel for success. The thinking goes back decades to Richard Bolles’s self-published 1972 classic “What Color is Your Parachute”. The thinking has inspired countless career aspirants, including business titans.

“You’ve got to find what you love. … The only way to do great work is to love what you do. If you haven’t found it yet, keep looking, and don’t settle,” related the late Apple founder Steve Jobs in a commencement address delivered in 2005 at Stanford (Calif.) University. For Mr. Jobs and others over the past 4 decades, the bedrock foundation of a career is passion for the work and dreaming the big dream.

Cal Newport, the author of “So Good They Can’t Ignore You” (New York: Business Plus, 2012), takes the polar opposite view. The job-passion trail has little to do with why most people love the work they do, and can spawn anxiety and a pattern of moving from one job to another, according to Mr. Newport. Rather, passion for the job comes after the hours of hard work that are needed to become really good at something. How the work is done is more important than what the work is.

In “Designing Your Life” (New York: Alfred A. Knopf, 2016), Bill Burnett and Dave Evans go even further, arguing that a career based on passion is usually useless and sometimes dangerous, since many people don’t know what they are passionate about or are passionate about something that is a clunker from a career perspective. Following your passion can lead to chasing pipe dreams.

A better tact might be to insert “interest” instead of “passion” when pondering career choices, according to Crystal Holly, PhD, a clinical psychologist in Ottawa. “Our careers are just one part of our lives, and not always the most important one,” she said in an interview for the article published on the website of the Canadian Broadcasting Corporation (CBC).

Looking at interests more abstractly, rather than setting up a score sheet of definitive career goals, can be helpful, according to career coach Jen Polk, PhD, since that approach can lead to work areas not previously considered, which prove to be satisfying and fulfilling.

The path of job passion worked for Steve Jobs. But it might not be the way for many people.

Click here to read the CBC article.

“Follow your passion” has long been a self-help mantra when it comes to a career. The idea has been that doing what you love will provide the fuel for success. The thinking goes back decades to Richard Bolles’s self-published 1972 classic “What Color is Your Parachute”. The thinking has inspired countless career aspirants, including business titans.

“You’ve got to find what you love. … The only way to do great work is to love what you do. If you haven’t found it yet, keep looking, and don’t settle,” related the late Apple founder Steve Jobs in a commencement address delivered in 2005 at Stanford (Calif.) University. For Mr. Jobs and others over the past 4 decades, the bedrock foundation of a career is passion for the work and dreaming the big dream.

Cal Newport, the author of “So Good They Can’t Ignore You” (New York: Business Plus, 2012), takes the polar opposite view. The job-passion trail has little to do with why most people love the work they do, and can spawn anxiety and a pattern of moving from one job to another, according to Mr. Newport. Rather, passion for the job comes after the hours of hard work that are needed to become really good at something. How the work is done is more important than what the work is.

In “Designing Your Life” (New York: Alfred A. Knopf, 2016), Bill Burnett and Dave Evans go even further, arguing that a career based on passion is usually useless and sometimes dangerous, since many people don’t know what they are passionate about or are passionate about something that is a clunker from a career perspective. Following your passion can lead to chasing pipe dreams.

A better tact might be to insert “interest” instead of “passion” when pondering career choices, according to Crystal Holly, PhD, a clinical psychologist in Ottawa. “Our careers are just one part of our lives, and not always the most important one,” she said in an interview for the article published on the website of the Canadian Broadcasting Corporation (CBC).

Looking at interests more abstractly, rather than setting up a score sheet of definitive career goals, can be helpful, according to career coach Jen Polk, PhD, since that approach can lead to work areas not previously considered, which prove to be satisfying and fulfilling.

The path of job passion worked for Steve Jobs. But it might not be the way for many people.

Click here to read the CBC article.

“Follow your passion” has long been a self-help mantra when it comes to a career. The idea has been that doing what you love will provide the fuel for success. The thinking goes back decades to Richard Bolles’s self-published 1972 classic “What Color is Your Parachute”. The thinking has inspired countless career aspirants, including business titans.

“You’ve got to find what you love. … The only way to do great work is to love what you do. If you haven’t found it yet, keep looking, and don’t settle,” related the late Apple founder Steve Jobs in a commencement address delivered in 2005 at Stanford (Calif.) University. For Mr. Jobs and others over the past 4 decades, the bedrock foundation of a career is passion for the work and dreaming the big dream.

Cal Newport, the author of “So Good They Can’t Ignore You” (New York: Business Plus, 2012), takes the polar opposite view. The job-passion trail has little to do with why most people love the work they do, and can spawn anxiety and a pattern of moving from one job to another, according to Mr. Newport. Rather, passion for the job comes after the hours of hard work that are needed to become really good at something. How the work is done is more important than what the work is.

In “Designing Your Life” (New York: Alfred A. Knopf, 2016), Bill Burnett and Dave Evans go even further, arguing that a career based on passion is usually useless and sometimes dangerous, since many people don’t know what they are passionate about or are passionate about something that is a clunker from a career perspective. Following your passion can lead to chasing pipe dreams.

A better tact might be to insert “interest” instead of “passion” when pondering career choices, according to Crystal Holly, PhD, a clinical psychologist in Ottawa. “Our careers are just one part of our lives, and not always the most important one,” she said in an interview for the article published on the website of the Canadian Broadcasting Corporation (CBC).

Looking at interests more abstractly, rather than setting up a score sheet of definitive career goals, can be helpful, according to career coach Jen Polk, PhD, since that approach can lead to work areas not previously considered, which prove to be satisfying and fulfilling.

The path of job passion worked for Steve Jobs. But it might not be the way for many people.

Click here to read the CBC article.

The Internet can be the antithesis of pondering before doing. “Take a breath,” “count to 10,” and “sleep on it” are all pearls of wisdom meant to keep people from doing or saying something that they will regret later. But the world of Facebook, Twitter, and WhatsApp is rife with rude responses and is a conduit for “virality” – the global dissemination of information.

The information can be silly and harmless. But it also can be false and damaging. A compelling example of the latter is the meddling in the 2016 U.S. presidential election by Russian operatives via Facebook.

The information also can prove lethal. An article in The Economist cites the example of at least two dozen people who were killed in India after stories linking them (falsely) to child abductions went viral on WhatsApp, a messaging service owned by Facebook.

Part of the problem with WhatsApp has been the capability of mass dissemination of a post. Users now are able to forward messages to only 20 others. Since WhatsApp is not fueled by advertiser revenue, a drop in traffic does not affect the financial bottom line. A similar limit on Facebook and Twitter seems harder to envision.

And yet, the move could prove wise, according to the article. “The short-term pain caused by a decline in virality may be in the long-term interest of the social networks. Fake news and concerns about digital addiction, among other things, have already damaged the reputations of tech platforms. Moves to slow sharing could help see off draconian action by regulators and lawmakers,” according to the authors.

More than half the population of the planet uses the Internet. Fostering a climate of honest exchange of information and limiting the spread of malicious information could have a transformative effect.

Click here to read The Economist article.

The Internet can be the antithesis of pondering before doing. “Take a breath,” “count to 10,” and “sleep on it” are all pearls of wisdom meant to keep people from doing or saying something that they will regret later. But the world of Facebook, Twitter, and WhatsApp is rife with rude responses and is a conduit for “virality” – the global dissemination of information.

The information can be silly and harmless. But it also can be false and damaging. A compelling example of the latter is the meddling in the 2016 U.S. presidential election by Russian operatives via Facebook.

The information also can prove lethal. An article in The Economist cites the example of at least two dozen people who were killed in India after stories linking them (falsely) to child abductions went viral on WhatsApp, a messaging service owned by Facebook.

Part of the problem with WhatsApp has been the capability of mass dissemination of a post. Users now are able to forward messages to only 20 others. Since WhatsApp is not fueled by advertiser revenue, a drop in traffic does not affect the financial bottom line. A similar limit on Facebook and Twitter seems harder to envision.

And yet, the move could prove wise, according to the article. “The short-term pain caused by a decline in virality may be in the long-term interest of the social networks. Fake news and concerns about digital addiction, among other things, have already damaged the reputations of tech platforms. Moves to slow sharing could help see off draconian action by regulators and lawmakers,” according to the authors.

More than half the population of the planet uses the Internet. Fostering a climate of honest exchange of information and limiting the spread of malicious information could have a transformative effect.

Click here to read The Economist article.

The Internet can be the antithesis of pondering before doing. “Take a breath,” “count to 10,” and “sleep on it” are all pearls of wisdom meant to keep people from doing or saying something that they will regret later. But the world of Facebook, Twitter, and WhatsApp is rife with rude responses and is a conduit for “virality” – the global dissemination of information.

The information can be silly and harmless. But it also can be false and damaging. A compelling example of the latter is the meddling in the 2016 U.S. presidential election by Russian operatives via Facebook.

The information also can prove lethal. An article in The Economist cites the example of at least two dozen people who were killed in India after stories linking them (falsely) to child abductions went viral on WhatsApp, a messaging service owned by Facebook.

Part of the problem with WhatsApp has been the capability of mass dissemination of a post. Users now are able to forward messages to only 20 others. Since WhatsApp is not fueled by advertiser revenue, a drop in traffic does not affect the financial bottom line. A similar limit on Facebook and Twitter seems harder to envision.

And yet, the move could prove wise, according to the article. “The short-term pain caused by a decline in virality may be in the long-term interest of the social networks. Fake news and concerns about digital addiction, among other things, have already damaged the reputations of tech platforms. Moves to slow sharing could help see off draconian action by regulators and lawmakers,” according to the authors.

More than half the population of the planet uses the Internet. Fostering a climate of honest exchange of information and limiting the spread of malicious information could have a transformative effect.

Click here to read The Economist article.

Nulliparous women who were induced at 39 weeks had the same relative risk of adverse perinatal outcomes but a lower risk of a cesarean delivery, compared with women who received expectant management, results that researchers say contrast traditional recommendations for perinatal care, according to study from the New England Journal of Medicine.

Michele G. Sullivan/Frontline Medical News

“These findings contradict the conclusions of multiple observational studies that have suggested that labor induction is associated with an increased risk of adverse maternal and perinatal outcomes,” William A. Grobman, MD, the Arthur Hale Curtis, MD, Professor of Obstetrics and Gynecology at Northwestern University in Chicago, and his colleagues wrote. “These studies, however, compared women who underwent labor induction with those who had spontaneous labor, which is not a comparison that is useful to guide clinical decision making.”

Dr. Grobman and his colleagues evaluated the deliveries of 3,062 women who underwent labor induction between 39 weeks of gestation and 39 weeks and 4 days of gestation, and compared them with outcomes of 3,044 women who received expectant management until 40 weeks and 5 days of gestation. Women in both groups had a singleton fetus, no indication of early delivery, and did not plan on delivering by C-section. The participants were assessed again at about 38 weeks of gestation and randomly assigned to receive labor induction or expectant management as part of a multicenter randomized, controlled, parallel-group, unmasked trial in 41 maternal-fetal medicine departments in hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development network screened between March 2014, and August 2017.

Primary perinatal outcomes and components were defined as perinatal death, respiratory support, an Apgar score of 3 or less at 5 minutes, hypoxic-ischemic encephalopathy, seizure, infection, meconium aspiration syndrome, birth trauma, intracranial or subgaleal hemorrhage, or hypotension that requires vasopressor support. The principal secondary outcome was cesarean delivery, but other secondary outcomes included neonatal or intensive care, infection, postpartum hospital stay, and hypertension, among others.

Dr. Grobman and his colleagues found 132 (4.3%) of neonates in the induction group and 164 (5.4%) in the expectant-management group experienced a primary composite outcome (relative risk, 0.80; 95% confidence interval, 0.64-1.00; P = .049).

Regarding secondary outcomes, there was a significantly lower risk of cesarean delivery in the induction group, with 18.6% of women undergoing a cesarean delivery, compared with 22.2% of women in the expectant-management group (RR, 0.84; 95% CI, 0.76-0.93; P less than .001). Women in the labor induction group had a significantly lower relative risk of hypertensive disorders of pregnancy (9.1%), compared with the expectant-management (14.1%) group (RR, 0.64; 95% CI, 0.56-0.74; P less than .001). The investigators said women who underwent induced labor had lower 10-point Likert scale scores, were more likely to have “extensions of the uterine incision during cesarean delivery,” perceived they had “more control” during delivery, and had a shorter postpartum stay in the hospital, compared with women who received expectant management. However, women in the induced labor group also had a longer stay in the labor and delivery units, they said.

The researchers noted the limitations in this study, which included its unmasked design, lack of power to detect infrequent outcome differences, and the lack of information surrounding labor induction at 39 weeks in low-risk nulliparous women.

“These results suggest that policies aimed at the avoidance of elective labor induction among low-risk nulliparous women at 39 weeks of gestation are unlikely to reduce the rate of cesarean delivery on a population level; the trial provides information that can be incorporated into discussions that rely on principles of shared decision making,” Dr. Grobman and his colleagues wrote.

This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Silver reports receiving personal fees from Gestavision. The other authors report no relevant financial disclosures.

SOURCE: Grobman WA et al. N Engl J Med. 2018 Aug 9. doi: 10.1056/NEJMoa1800566.

Nulliparous women who were induced at 39 weeks had the same relative risk of adverse perinatal outcomes but a lower risk of a cesarean delivery, compared with women who received expectant management, results that researchers say contrast traditional recommendations for perinatal care, according to study from the New England Journal of Medicine.

Michele G. Sullivan/Frontline Medical News

“These findings contradict the conclusions of multiple observational studies that have suggested that labor induction is associated with an increased risk of adverse maternal and perinatal outcomes,” William A. Grobman, MD, the Arthur Hale Curtis, MD, Professor of Obstetrics and Gynecology at Northwestern University in Chicago, and his colleagues wrote. “These studies, however, compared women who underwent labor induction with those who had spontaneous labor, which is not a comparison that is useful to guide clinical decision making.”

Dr. Grobman and his colleagues evaluated the deliveries of 3,062 women who underwent labor induction between 39 weeks of gestation and 39 weeks and 4 days of gestation, and compared them with outcomes of 3,044 women who received expectant management until 40 weeks and 5 days of gestation. Women in both groups had a singleton fetus, no indication of early delivery, and did not plan on delivering by C-section. The participants were assessed again at about 38 weeks of gestation and randomly assigned to receive labor induction or expectant management as part of a multicenter randomized, controlled, parallel-group, unmasked trial in 41 maternal-fetal medicine departments in hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development network screened between March 2014, and August 2017.

Primary perinatal outcomes and components were defined as perinatal death, respiratory support, an Apgar score of 3 or less at 5 minutes, hypoxic-ischemic encephalopathy, seizure, infection, meconium aspiration syndrome, birth trauma, intracranial or subgaleal hemorrhage, or hypotension that requires vasopressor support. The principal secondary outcome was cesarean delivery, but other secondary outcomes included neonatal or intensive care, infection, postpartum hospital stay, and hypertension, among others.

Dr. Grobman and his colleagues found 132 (4.3%) of neonates in the induction group and 164 (5.4%) in the expectant-management group experienced a primary composite outcome (relative risk, 0.80; 95% confidence interval, 0.64-1.00; P = .049).

Regarding secondary outcomes, there was a significantly lower risk of cesarean delivery in the induction group, with 18.6% of women undergoing a cesarean delivery, compared with 22.2% of women in the expectant-management group (RR, 0.84; 95% CI, 0.76-0.93; P less than .001). Women in the labor induction group had a significantly lower relative risk of hypertensive disorders of pregnancy (9.1%), compared with the expectant-management (14.1%) group (RR, 0.64; 95% CI, 0.56-0.74; P less than .001). The investigators said women who underwent induced labor had lower 10-point Likert scale scores, were more likely to have “extensions of the uterine incision during cesarean delivery,” perceived they had “more control” during delivery, and had a shorter postpartum stay in the hospital, compared with women who received expectant management. However, women in the induced labor group also had a longer stay in the labor and delivery units, they said.

The researchers noted the limitations in this study, which included its unmasked design, lack of power to detect infrequent outcome differences, and the lack of information surrounding labor induction at 39 weeks in low-risk nulliparous women.

“These results suggest that policies aimed at the avoidance of elective labor induction among low-risk nulliparous women at 39 weeks of gestation are unlikely to reduce the rate of cesarean delivery on a population level; the trial provides information that can be incorporated into discussions that rely on principles of shared decision making,” Dr. Grobman and his colleagues wrote.

This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Silver reports receiving personal fees from Gestavision. The other authors report no relevant financial disclosures.

SOURCE: Grobman WA et al. N Engl J Med. 2018 Aug 9. doi: 10.1056/NEJMoa1800566.

Nulliparous women who were induced at 39 weeks had the same relative risk of adverse perinatal outcomes but a lower risk of a cesarean delivery, compared with women who received expectant management, results that researchers say contrast traditional recommendations for perinatal care, according to study from the New England Journal of Medicine.

Michele G. Sullivan/Frontline Medical News

“These findings contradict the conclusions of multiple observational studies that have suggested that labor induction is associated with an increased risk of adverse maternal and perinatal outcomes,” William A. Grobman, MD, the Arthur Hale Curtis, MD, Professor of Obstetrics and Gynecology at Northwestern University in Chicago, and his colleagues wrote. “These studies, however, compared women who underwent labor induction with those who had spontaneous labor, which is not a comparison that is useful to guide clinical decision making.”

Dr. Grobman and his colleagues evaluated the deliveries of 3,062 women who underwent labor induction between 39 weeks of gestation and 39 weeks and 4 days of gestation, and compared them with outcomes of 3,044 women who received expectant management until 40 weeks and 5 days of gestation. Women in both groups had a singleton fetus, no indication of early delivery, and did not plan on delivering by C-section. The participants were assessed again at about 38 weeks of gestation and randomly assigned to receive labor induction or expectant management as part of a multicenter randomized, controlled, parallel-group, unmasked trial in 41 maternal-fetal medicine departments in hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development network screened between March 2014, and August 2017.

Primary perinatal outcomes and components were defined as perinatal death, respiratory support, an Apgar score of 3 or less at 5 minutes, hypoxic-ischemic encephalopathy, seizure, infection, meconium aspiration syndrome, birth trauma, intracranial or subgaleal hemorrhage, or hypotension that requires vasopressor support. The principal secondary outcome was cesarean delivery, but other secondary outcomes included neonatal or intensive care, infection, postpartum hospital stay, and hypertension, among others.

Dr. Grobman and his colleagues found 132 (4.3%) of neonates in the induction group and 164 (5.4%) in the expectant-management group experienced a primary composite outcome (relative risk, 0.80; 95% confidence interval, 0.64-1.00; P = .049).

Regarding secondary outcomes, there was a significantly lower risk of cesarean delivery in the induction group, with 18.6% of women undergoing a cesarean delivery, compared with 22.2% of women in the expectant-management group (RR, 0.84; 95% CI, 0.76-0.93; P less than .001). Women in the labor induction group had a significantly lower relative risk of hypertensive disorders of pregnancy (9.1%), compared with the expectant-management (14.1%) group (RR, 0.64; 95% CI, 0.56-0.74; P less than .001). The investigators said women who underwent induced labor had lower 10-point Likert scale scores, were more likely to have “extensions of the uterine incision during cesarean delivery,” perceived they had “more control” during delivery, and had a shorter postpartum stay in the hospital, compared with women who received expectant management. However, women in the induced labor group also had a longer stay in the labor and delivery units, they said.

The researchers noted the limitations in this study, which included its unmasked design, lack of power to detect infrequent outcome differences, and the lack of information surrounding labor induction at 39 weeks in low-risk nulliparous women.

“These results suggest that policies aimed at the avoidance of elective labor induction among low-risk nulliparous women at 39 weeks of gestation are unlikely to reduce the rate of cesarean delivery on a population level; the trial provides information that can be incorporated into discussions that rely on principles of shared decision making,” Dr. Grobman and his colleagues wrote.

This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Silver reports receiving personal fees from Gestavision. The other authors report no relevant financial disclosures.

SOURCE: Grobman WA et al. N Engl J Med. 2018 Aug 9. doi: 10.1056/NEJMoa1800566.

Woman sunbathing

New research suggests people who develop frequent cases of basal cell carcinoma (BCC) have an increased risk of leukemias, lymphomas, and other cancers.

“We discovered that people who develop 6 or more basal cell carcinomas during a 10-year period are about 3 times more likely than the general population to develop other, unrelated cancers,” said Kavita Sarin, MD, PhD, of Stanford University School of Medicine in California.

“We’re hopeful that this finding could be a way to identify people at an increased risk for a life-threatening malignancy before those cancers develop.”

Dr Sarin and her colleagues reported their findings in JCI Insight.

Stanford cohort

The researchers first studied 61 patients treated at Stanford Health Care for unusually frequent BCCs—an average of 11 per patient over a 10-year period. The team investigated whether these patients may have mutations in 29 genes that code for DNA damage repair proteins.

“We found that about 20% of the people with frequent basal cell carcinomas have a mutation in one of the genes responsible for repairing DNA damage, versus about 3% of the general population,” Dr Sarin said. “That’s shockingly high.”

Specifically, there were 12 BCC patients (19.7%) who had 13 pathogenic mutations in 12 genes—APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN, and PALB2. And 3.0% of non-Finnish European subjects in the Exome Aggregation Consortium had pathogenic mutations in these 12 genes.

Furthermore, 21 of the 61 BCC patients (64.4%) had a history of additional cancers. This included 5 hematologic malignancies (leukemia/lymphoma), 5 invasive melanomas, and 2 breast, 2 colon, and 5 prostate cancers.

When the researchers compared the cancer prevalence in these patients to the Surveillance, Epidemiology, and End Results-estimated prevalence of cancer in the 60- to 69-year-old population of European descent, the BCC cohort had an increased risk of any cancer—a relative risk (RR) of 3.5 (P<0.001).

The RR was 3.5 for leukemia and lymphoma (P=0.004), 11.9 for invasive melanoma (P<0.001), 4.5 for colon cancer (P=0.030), 5.6 for breast cancer (P=0.009), and 4.7 for prostate cancer (P<0.001).

Insurance cohort

To confirm the findings in the Stanford cohort, the researchers applied a similar analysis to a large medical insurance claims database, Truven MarketScan.

The database contained 111,562 patients with 1 case of BCC, 13,264 patients with 6 or more BCCs, and 2920 patients with 12 or more BCCs. Truven patients with no history of BCC served as controls.

The researchers adjusted for age and sex and found that patients with 1 BCC, 6 or more BCCs, and 12 or more BCCs had an increased risk of any cancer compared to controls.

The odds ratio (OR) for any cancer was 1.61 for patients with 1 BCC, 3.12 for those with 6 or more BCCs, and 4.15 for patients with 12 or more BCCs.

The OR for Hodgkin lymphoma was 2.27 for patients with 1 BCC, 8.94 for patients with 6 or more BCCs, and 15.41 for patients with 12 or more BCCs.

The OR for non-Hodgkin lymphoma was 1.40 for patients with 1 BCC, 2.59 for patients with 6 or more BCCs, and 3.10 for patients with 12 or more BCCs.

The OR for leukemia was 1.76 for patients with 1 BCC, 3.23 for patients with 6 or more BCCs, and 5.78 for patients with 12 or more BCCs.

The researchers pointed out that, the more BCCs an individual had, the more likely that person was to have had other cancers as well.

“I was surprised to see such a strong correlation, but it’s also very gratifying,” Dr Sarin said. “Now, we can ask patients with repeated basal cell carcinomas whether they have family members with other types of cancers and perhaps suggest that they consider genetic testing and increased screening.”

The researchers are continuing to enroll Stanford patients in their study to learn whether particular mutations in genes responsible for repairing DNA damage are linked to the development of specific malignancies. The team would also like to conduct a similar study in patients with frequent melanomas.

The current study was supported by the Dermatology Foundation, the Stanford Society of Physician Scholars, the American Skin Association, and Pellepharm Inc.

Woman sunbathing

New research suggests people who develop frequent cases of basal cell carcinoma (BCC) have an increased risk of leukemias, lymphomas, and other cancers.

“We discovered that people who develop 6 or more basal cell carcinomas during a 10-year period are about 3 times more likely than the general population to develop other, unrelated cancers,” said Kavita Sarin, MD, PhD, of Stanford University School of Medicine in California.

“We’re hopeful that this finding could be a way to identify people at an increased risk for a life-threatening malignancy before those cancers develop.”

Dr Sarin and her colleagues reported their findings in JCI Insight.

Stanford cohort

The researchers first studied 61 patients treated at Stanford Health Care for unusually frequent BCCs—an average of 11 per patient over a 10-year period. The team investigated whether these patients may have mutations in 29 genes that code for DNA damage repair proteins.

“We found that about 20% of the people with frequent basal cell carcinomas have a mutation in one of the genes responsible for repairing DNA damage, versus about 3% of the general population,” Dr Sarin said. “That’s shockingly high.”

Specifically, there were 12 BCC patients (19.7%) who had 13 pathogenic mutations in 12 genes—APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN, and PALB2. And 3.0% of non-Finnish European subjects in the Exome Aggregation Consortium had pathogenic mutations in these 12 genes.

Furthermore, 21 of the 61 BCC patients (64.4%) had a history of additional cancers. This included 5 hematologic malignancies (leukemia/lymphoma), 5 invasive melanomas, and 2 breast, 2 colon, and 5 prostate cancers.

When the researchers compared the cancer prevalence in these patients to the Surveillance, Epidemiology, and End Results-estimated prevalence of cancer in the 60- to 69-year-old population of European descent, the BCC cohort had an increased risk of any cancer—a relative risk (RR) of 3.5 (P<0.001).

The RR was 3.5 for leukemia and lymphoma (P=0.004), 11.9 for invasive melanoma (P<0.001), 4.5 for colon cancer (P=0.030), 5.6 for breast cancer (P=0.009), and 4.7 for prostate cancer (P<0.001).

Insurance cohort

To confirm the findings in the Stanford cohort, the researchers applied a similar analysis to a large medical insurance claims database, Truven MarketScan.

The database contained 111,562 patients with 1 case of BCC, 13,264 patients with 6 or more BCCs, and 2920 patients with 12 or more BCCs. Truven patients with no history of BCC served as controls.

The researchers adjusted for age and sex and found that patients with 1 BCC, 6 or more BCCs, and 12 or more BCCs had an increased risk of any cancer compared to controls.

The odds ratio (OR) for any cancer was 1.61 for patients with 1 BCC, 3.12 for those with 6 or more BCCs, and 4.15 for patients with 12 or more BCCs.

The OR for Hodgkin lymphoma was 2.27 for patients with 1 BCC, 8.94 for patients with 6 or more BCCs, and 15.41 for patients with 12 or more BCCs.

The OR for non-Hodgkin lymphoma was 1.40 for patients with 1 BCC, 2.59 for patients with 6 or more BCCs, and 3.10 for patients with 12 or more BCCs.

The OR for leukemia was 1.76 for patients with 1 BCC, 3.23 for patients with 6 or more BCCs, and 5.78 for patients with 12 or more BCCs.

The researchers pointed out that, the more BCCs an individual had, the more likely that person was to have had other cancers as well.

“I was surprised to see such a strong correlation, but it’s also very gratifying,” Dr Sarin said. “Now, we can ask patients with repeated basal cell carcinomas whether they have family members with other types of cancers and perhaps suggest that they consider genetic testing and increased screening.”

The researchers are continuing to enroll Stanford patients in their study to learn whether particular mutations in genes responsible for repairing DNA damage are linked to the development of specific malignancies. The team would also like to conduct a similar study in patients with frequent melanomas.

The current study was supported by the Dermatology Foundation, the Stanford Society of Physician Scholars, the American Skin Association, and Pellepharm Inc.

Woman sunbathing

New research suggests people who develop frequent cases of basal cell carcinoma (BCC) have an increased risk of leukemias, lymphomas, and other cancers.

“We discovered that people who develop 6 or more basal cell carcinomas during a 10-year period are about 3 times more likely than the general population to develop other, unrelated cancers,” said Kavita Sarin, MD, PhD, of Stanford University School of Medicine in California.

“We’re hopeful that this finding could be a way to identify people at an increased risk for a life-threatening malignancy before those cancers develop.”

Dr Sarin and her colleagues reported their findings in JCI Insight.

Stanford cohort

The researchers first studied 61 patients treated at Stanford Health Care for unusually frequent BCCs—an average of 11 per patient over a 10-year period. The team investigated whether these patients may have mutations in 29 genes that code for DNA damage repair proteins.

“We found that about 20% of the people with frequent basal cell carcinomas have a mutation in one of the genes responsible for repairing DNA damage, versus about 3% of the general population,” Dr Sarin said. “That’s shockingly high.”

Specifically, there were 12 BCC patients (19.7%) who had 13 pathogenic mutations in 12 genes—APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN, and PALB2. And 3.0% of non-Finnish European subjects in the Exome Aggregation Consortium had pathogenic mutations in these 12 genes.

Furthermore, 21 of the 61 BCC patients (64.4%) had a history of additional cancers. This included 5 hematologic malignancies (leukemia/lymphoma), 5 invasive melanomas, and 2 breast, 2 colon, and 5 prostate cancers.

When the researchers compared the cancer prevalence in these patients to the Surveillance, Epidemiology, and End Results-estimated prevalence of cancer in the 60- to 69-year-old population of European descent, the BCC cohort had an increased risk of any cancer—a relative risk (RR) of 3.5 (P<0.001).

The RR was 3.5 for leukemia and lymphoma (P=0.004), 11.9 for invasive melanoma (P<0.001), 4.5 for colon cancer (P=0.030), 5.6 for breast cancer (P=0.009), and 4.7 for prostate cancer (P<0.001).

Insurance cohort

To confirm the findings in the Stanford cohort, the researchers applied a similar analysis to a large medical insurance claims database, Truven MarketScan.

The database contained 111,562 patients with 1 case of BCC, 13,264 patients with 6 or more BCCs, and 2920 patients with 12 or more BCCs. Truven patients with no history of BCC served as controls.

The researchers adjusted for age and sex and found that patients with 1 BCC, 6 or more BCCs, and 12 or more BCCs had an increased risk of any cancer compared to controls.

The odds ratio (OR) for any cancer was 1.61 for patients with 1 BCC, 3.12 for those with 6 or more BCCs, and 4.15 for patients with 12 or more BCCs.

The OR for Hodgkin lymphoma was 2.27 for patients with 1 BCC, 8.94 for patients with 6 or more BCCs, and 15.41 for patients with 12 or more BCCs.

The OR for non-Hodgkin lymphoma was 1.40 for patients with 1 BCC, 2.59 for patients with 6 or more BCCs, and 3.10 for patients with 12 or more BCCs.

The OR for leukemia was 1.76 for patients with 1 BCC, 3.23 for patients with 6 or more BCCs, and 5.78 for patients with 12 or more BCCs.

The researchers pointed out that, the more BCCs an individual had, the more likely that person was to have had other cancers as well.

“I was surprised to see such a strong correlation, but it’s also very gratifying,” Dr Sarin said. “Now, we can ask patients with repeated basal cell carcinomas whether they have family members with other types of cancers and perhaps suggest that they consider genetic testing and increased screening.”

The researchers are continuing to enroll Stanford patients in their study to learn whether particular mutations in genes responsible for repairing DNA damage are linked to the development of specific malignancies. The team would also like to conduct a similar study in patients with frequent melanomas.

The current study was supported by the Dermatology Foundation, the Stanford Society of Physician Scholars, the American Skin Association, and Pellepharm Inc.

After just 4 months, the National Institute of Alcohol Abuse and Alcoholism (NIAAA) is ending funding for the Moderate Alcohol and Cardiovascular Health (MACH) trial, citing concerns about the study design.

The MACH study was designed as a multicenter randomized trial to determine the effects of 1 serving of alcohol (approximately 15 g) a day compared with no alcohol intake on the rate of new cases of cardiovascular disease and new cases of diabetes among participants free of diabetes at baseline. The study was launched because some epidemiologic research had shown that moderate alcohol consumption had health benefits by reducing risk for coronary artery disease, type 2 diabetes, and rheumatoid arthritis.

The study began enrollment in February 2018 and was suspended on May 10. The NIAAA expected to commit $20 million to the project over 10 years, of which $4 million has been spent; remaining funding came from private donations of $67.7 million, of which $11.8 million has been spent.

The “orderly closeout” is based on recommendations from the advisory committee to the director working group, which found “significant process irregularities in the development of funding opportunities for the MACH funding awards undermined the integrity of the research process.” Additionally, a preliminary report from the National Institutes of Health (NIH) Office of Management Assessment determined that a small number of NIAAA employees violated NIH policies in soliciting gift funding and circumvented standard operating procedures.

After just 4 months, the National Institute of Alcohol Abuse and Alcoholism (NIAAA) is ending funding for the Moderate Alcohol and Cardiovascular Health (MACH) trial, citing concerns about the study design.

The MACH study was designed as a multicenter randomized trial to determine the effects of 1 serving of alcohol (approximately 15 g) a day compared with no alcohol intake on the rate of new cases of cardiovascular disease and new cases of diabetes among participants free of diabetes at baseline. The study was launched because some epidemiologic research had shown that moderate alcohol consumption had health benefits by reducing risk for coronary artery disease, type 2 diabetes, and rheumatoid arthritis.

The study began enrollment in February 2018 and was suspended on May 10. The NIAAA expected to commit $20 million to the project over 10 years, of which $4 million has been spent; remaining funding came from private donations of $67.7 million, of which $11.8 million has been spent.

The “orderly closeout” is based on recommendations from the advisory committee to the director working group, which found “significant process irregularities in the development of funding opportunities for the MACH funding awards undermined the integrity of the research process.” Additionally, a preliminary report from the National Institutes of Health (NIH) Office of Management Assessment determined that a small number of NIAAA employees violated NIH policies in soliciting gift funding and circumvented standard operating procedures.

After just 4 months, the National Institute of Alcohol Abuse and Alcoholism (NIAAA) is ending funding for the Moderate Alcohol and Cardiovascular Health (MACH) trial, citing concerns about the study design.

The MACH study was designed as a multicenter randomized trial to determine the effects of 1 serving of alcohol (approximately 15 g) a day compared with no alcohol intake on the rate of new cases of cardiovascular disease and new cases of diabetes among participants free of diabetes at baseline. The study was launched because some epidemiologic research had shown that moderate alcohol consumption had health benefits by reducing risk for coronary artery disease, type 2 diabetes, and rheumatoid arthritis.

The study began enrollment in February 2018 and was suspended on May 10. The NIAAA expected to commit $20 million to the project over 10 years, of which $4 million has been spent; remaining funding came from private donations of $67.7 million, of which $11.8 million has been spent.

The “orderly closeout” is based on recommendations from the advisory committee to the director working group, which found “significant process irregularities in the development of funding opportunities for the MACH funding awards undermined the integrity of the research process.” Additionally, a preliminary report from the National Institutes of Health (NIH) Office of Management Assessment determined that a small number of NIAAA employees violated NIH policies in soliciting gift funding and circumvented standard operating procedures.