Citations

Abstract Background Less than 3% of older patients with cancer are enrolled in clinical trials. To reverse this underrepresentation, we compared older patients enrolled with older-patient-specific trials, defined as those designed for older patients with cancer, with those enrolled in age-unspecified trials. Materials and Methods We focused on individual patient data from those ≥65 years (younger patients excluded) and included all Alliance phase III adjuvant breast cancer trials from 1985–2012. Results Among 2,277 patients, 1,014 had been enrolled to older-patient-specific and 1,263 to age-unspecified trials. The median age (range) in the older-patient-specific trials was 72 (65–89) years compared with 68 (65–84) years in the cohort of older patients in age-unspecified trials; p < .0001. A greater percentage of patients 75 years or older had enrolled in older-patient-specific trials compared with the cohort of age-unspecified trials: 26% versus 6% (p < .0001). Median overall survival (OS) was 12.8 years (95% confidence interval [CI], 11.9–13.7) and 13.5 years (95% CI, 12.9–14.1) for older-patient-specific and age-unspecified trials, respectively. OS was comparable (hazard ratio [HR], 1.08; 95% CI, 0.92–1.28; p = .34; referent: age-unspecified trials), after adjusting for age, estrogen receptor status, tumor size, and lymph node status. Similar findings were reached for recurrence-free survival. A lower rate of grade 3–5 adverse events (hematologic and nonhematologic) was reported in older-patient-specific trials (43% vs. 58%; p < .0001). Sensitivity analysis with chemotherapy only trials and subset analysis, adjusted for performance score, yielded similar OS results. Conclusion Older-patient-specific trials appear to address this underrepresentation of older patients with ostensibly comparable outcomes. Clinical trial identification numbers. NCT00003088 (CALGB 9741); NCT00024102 (CALGB 49907); NCT00068601 (CALGB 40401); NCT00005970 (NCCTG N9831)

Significance Ebolaviruses belong to the group of nonsegmented negative strand (NNS) RNA viruses. Most members of the Ebolavirus genus cause severe disease in humans. Here, we report that ebolaviruses have evolved a genome replication mechanism that distinguishes them from the other NNS RNA viruses. The ebolavirus replication strategy includes the addition of a nontemplated 3′ nucleotide at the genome ends which may aid in avoiding antiviral recognition. Our data highlight the need for more research on NNS RNA virus replication strategies to reveal commonalities between virus families as well as unique features. Dissecting the replication mechanisms of NNS RNA viruses, including ebolaviruses, paves the way for the development of broad-spectrum antivirals that target the viral replication complexes, thereby preventing virus amplification.

Purpose The purpose of this study was to examine the relationship between manifestations of racism in medical school and subsequent changes in graduating medical students’ intentions to practice in underserved or minority communities, compared with their attitudes and intentions at matriculation. Method The authors used repeated-measures data from a longitudinal study of 3,756 students at 49 U.S. medical schools that were collected from 2010 to 2014. They conducted generalized linear mixed models to estimate whether manifestations of racism in school curricula/policies, school culture/climate, or student attitudes/behaviors predicted first- to fourth-year changes in students’ intentions to practice in underserved communities or primarily with minority populations. Analyses were stratified by students’ practice intentions (no/undecided/yes) at matriculation. Results Students’ more negative explicit racial attitudes were associated with decreased intention to practice with underserved or minority populations at graduation. Service learning experiences and a curriculum focused on improving minority health were associated with increased intention to practice in underserved communities. A curriculum focused on minority health/disparities, students’ perceived skill at developing relationships with minority patients, the proportion of minority students at the school, and the perception of a tense interracial environment were all associated with increased intention to care for minority patients. Conclusions This study provides evidence that racism manifested at multiple levels in medical schools was associated with graduating students’ decisions to provide care in high-need communities. Strategies to identify and eliminate structural racism and its manifestations in medical school are needed.

Abstract Objectives Given the increased complexity of molecular and cytogenetic testing (MOL-CG), the Society for Hematopathology Education Committee (SH-EC) was interested in determining what the current expectations are for MOL-CG education in hematopathology (HP) fellowship training. Methods The SH-EC sent a questionnaire to HP fellowship program directors (HP-PDs) covering MOL-CG training curricula, test menus, faculty background, teaching, and sign-out roles. These findings were explored via a panel-based discussion at the 2018 SH-EC meeting for HP-PDs. Results HP fellows are expected to understand basic principles, nomenclature, and indications for and limitations of testing. Interpretation of common assays is within that scope, but not necessarily proficiency in technical troubleshooting of testing or analysis of complex raw data. Conclusions The consensus was that HP fellows should understand the components of MOL-CG testing necessary to incorporate those results into an accurate, clinically relevant, and integrated HP report.

Abstract Background Little is known about patterns of and factors associated with treatment for de novo metastatic cancer patients who die soon after diagnosis. In this study, we examine treatment patterns for patients newly diagnosed with metastatic lung, colorectal, breast, or pancreatic cancer who died within 1 month of diagnosis. Methods We identified 100 848 adult patients in the National Cancer Database with de novo metastatic lung, colorectal, breast, and pancreatic cancer, diagnosed between 2004 and 2014 and who died within 1 month. We performed descriptive and multivariable logistic regression analyses to examine receipt of surgery, chemotherapy, radiation, and hormonal therapy by cancer type, adjusting for sociodemographic and clinical variables. Results Treatment substantially varied by cancer type, over time, age, insurance, and facility type. Surgery ranged from 0.4% in pancreatic to 28.3% in colorectal cancer (CRC) patients, chemotherapy from 5.8% among CRC to 11% in lung and breast cancer patients, and radiotherapy from 1.3% in pancreatic to 18.7% in lung cancer patients. Use of some treatments (eg, surgery for CRC and breast cancer) progressively declined between 2004 and 2014. Compared with lung cancer patients treated at National Cancer Institute-designated cancer centers, those treated at community cancer centers had 48% lower odds of radiation. Conclusions Treatment of patients diagnosed with imminently fatal de novo metastatic cancer varied markedly by cancer type and patient/facility characteristics. These variations warrant more research to better identify patients with imminently fatal de novo metastatic cancer who may not benefit from aggressive and expensive therapies.

PURPOSE CALGB/SWOG 80405 was a randomized phase III trial that found no statistically significant difference in overall survival (OS) in patients with first-line metastatic colorectal cancer treated with chemotherapy plus either bevacizumab or cetuximab. Primary tumor DNA from 843 patients has been used to discover genetic markers of OS. PATIENTS AND METHODS Gene mutations were determined by polymerase chain reaction. Microsatellite status was determined by genotyping of microsatellites. Tumor mutational burden (TMB) was determined by next-generation sequencing. Cox proportional hazard models were used, with adjusting factors. Interaction of molecular alterations with either the bevacizumab or the cetuximab arms was tested. RESULTS Patients with high TMB in their tumors had longer OS than did patients with low TMB (hazard ratio [HR], 0.73 [95% CI, 0.57 to 0.95]; P = .02). In patients with microsatellite instability–high (MSI-H) tumors, longer OS was observed in the bevacizumab arm than in the cetuximab arm (HR, 0.13 [95% CI, 0.06 to 0.30]; interaction P < .001 for interaction between microsatellite status and the two arms). Patients with BRAF mutant tumors had shorter OS than did patients with wild-type (WT) tumors (HR, 2.01 [95% CI, 1.49 to 2.71]; P < .001). Patients with extended RAS mutant tumors had shorter OS than did patients with WT tumors (HR, 1.52 [95% CI, 1.26 to 1.84]; P < .001). Patients with triple-negative tumors (WT for NRAS/ KRAS/ BRAF) had a median OS of 35.9 months (95% CI, 33.0 to 38.8 months) versus 22.2 months (95% CI, 19.6 to 24.4 months ) in patients with at least one mutated gene in their tumors ( P < .001). CONCLUSION In patients with metastatic colorectal cancer treated in first line, low TMB, and BRAF and RAS mutations are negative prognostic factors. Patients with MSI-H tumors benefited more from bevacizumab than from cetuximab, and studies to confirm this effect of MSI-H are warranted.

PURPOSE Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer to the CNS are limited. We previously reported modest activity of neratinib monotherapy for HER2-positive breast cancer brain metastases. Here we report the results from additional study cohorts. PATIENTS AND METHODS Patients with measurable, progressive, HER2-positive brain metastases (92% after receiving CNS surgery and/or radiotherapy) received neratinib 240 mg orally once per day plus capecitabine 750 mg/m 2 twice per day for 14 days, then 7 days off. Lapatinib-naïve (cohort 3A) and lapatinib-treated (cohort 3B) patients were enrolled. If nine or more of 35 (cohort 3A) or three or more of 25 (cohort 3B) had CNS objective response rates (ORR), the drug combination would be deemed promising. The primary end point was composite CNS ORR in each cohort separately, requiring a reduction of 50% or more in the sum of target CNS lesion volumes without progression of nontarget lesions, new lesions, escalating steroids, progressive neurologic signs or symptoms, or non-CNS progression. RESULTS Forty-nine patients enrolled in cohorts 3A (n = 37) and 3B (n = 12; cohort closed for slow accrual). In cohort 3A, the composite CNS ORR = 49% (95% CI, 32% to 66%), and the CNS ORR in cohort 3B = 33% (95% CI, 10% to 65%). Median progression-free survival was 5.5 and 3.1 months in cohorts 3A and 3B, respectively; median survival was 13.3 and 15.1 months. Diarrhea was the most common grade 3 toxicity (29% in cohorts 3A and 3B). Neratinib plus capecitabine is active against refractory, HER2-positive breast cancer brain metastases, adding additional evidence that the efficacy of HER2-directed therapy in the brain is enhanced by chemotherapy. For optimal tolerance, efforts to minimize diarrhea are warranted.

The diagnosis and management of cardiovascular disease (CVD) in competitive athletes represent a fundamental responsibility of the sports medicine community. Following the diagnosis of a CVD in a competitive athlete, it is the responsibility of the sports medicine team to delineate an effective treatment and management strategy that places the health and wellness of the athlete as the primary objective. An essential and often challenging aspect of this process is determining the appropriateness of continued participation ( i.e., “return-to-play”) in competitive athletics. Recently, a joint American Heart Association and American College of Cardiology Scientific Statement delineating sports eligibility supports a more patient-centered care model that supports shared decision making for clinicians and their patients/families. The present document was written to summarize the changing sports cardiology landscape with an aim of providing the cardiology and sports medicine communities with some practical approaches to eligibility decision making for competitive athletes with heart disease.

Objectives: Recent evidence suggests that music therapy, a holistic method of care, potentially is beneficial for symptom management. This quality improvement project aimed to evaluate the effect of music therapy on symptom management and coping skills of patients receiving palliative care and to measure patient satisfaction with the therapy. A secondary aim was to evaluate staff perception of patient outcomes of music therapy services. Methods: Palliative care clinicians attended a 30-minute education session on music therapy before the project was initiated. Study participants were patients and their families who were cared for by the inpatient palliative care consulting service at Mayo Clinic (Rochester, Minnesota) from June 1 through December 31, 2016. Patients were eligible if they required ongoing management of pain and anxiety or needed adaptive coping strategies. Patients and families were asked to complete a survey after each music therapy session. Staff were asked to complete a survey after completion of the project. Results: Music therapy was provided to 57 patients and 53 family members. Patient surveys indicated a decrease in anxiety and pain. All patients reported that music therapy facilitated stress relief, relaxation, pain relief, spiritual support, emotional support, and a general feeling of wellness. All participants recommended music therapy services for others. Palliative care clinicians reported that music therapy added value as a holistic service. Conclusions: In this quality improvement project, music therapy positively affected multiple domains of well-being for patients receiving palliative care.