Jatoi, Aminah

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)

Abstract Background Cachexia has significant impact on the patients' quality of life and prognosis. It is frequently observed in patients with cancer, especially in advanced stages, but prevalence data for the overall population are lacking. Good quality estimates of cancer cachexia in general and for each of the major cancer types would be highly relevant for potential treatment development efforts in this field. Both the USA and European Union (EU) have implemented special clinical development rules for such rare disorders what are called ‘orphan diseases’. The cut‐off level for a disease to be considered an orphan disease in the USA is 200 000 people (0.06% of the population) and EU is 5 per 10 000 people (0.05% of the population). Methods For this systematic review, we searched at PubMed (from inception to 31 January 2018) to identify clinical studies that assessed the prevalence of cachexia in cancer patients at risk. Studies reporting the prevalence of either cancer cachexia or wasting disease in the top‐10 cancer types and 4 other selected cancer types known to be particularly commonly complicated by cachexia were included in this analysis (i.e. prostate cancer, breast cancer, colorectal cancer, melanoma, endometrial cancer, thyroid cancer, urinary bladder cancer, non‐hodgkin lymphoma, lung cancer, kidney and renal pelvis cancer, head and neck cancer, gastric cancer, liver cancer, and pancreatic cancer). We calculated the current burden of cancer cachexia, disease by disease, in the USA and in the EU and compared them to the current guidelines for the definition of orphan disease status. Results We estimate that in 2014 in the USA, a total of 527 100 patients (16.5 subjects per 10 000 people of the total population), and in 2013 in the EU, a total of 800 300 patients (15.8 subjects per 10 000 people of the total population) suffered from cancer cachexia (of any kind). In the 14 separately analysed cancer types, the prevalence of cancer cachexia in the USA ranged between 11 300 (0.4/10 000, gastric cancer) and 92 000 patients (2.9/10 000, lung cancer) and in the EU between 14 300 (0.3/10 000, melanoma of the skin) and 150 100 (3.0/10 000, colorectal cancer). Conclusions The absolute number of patients affected by cancer cachexia in each cancer group is lower than the defined thresholds for orphan diseases in the USA and EU. Cancer cachexia in each subgroup separately should be considered an orphan disease.

Abstract Background: Chemotherapy-induced peripheral neuropathy is characterized by pain, numbness, and tingling in the hands and feet and by diminished quality of life. Multiple previous studies, mostly preclinical, suggest that poly (ADP-ribose) polymerase (PARP) inhibitors may help with these symptoms. Objective: To assess the relationship between PARP inhibition and prevention/palliation of peripheral neuropathy in a clinical setting. Design: Meta-analysis of placebo-controlled clinical trials with PARP inhibitors. Setting/Subjects: We conducted 9 literature searches that included PubMed and other sources to compile fully published placebo-controlled clinical trials that tested PARP inhibitors and that reported on peripheral neuropathy. Measurements: The relative risks for neuropathy of all grades based on PARP inhibition were calculated for each trial. Each trial was weighted by its respective sample size. A forest plot was constructed. Results: Five trials, inclusive of 843 patients, met this study's eligibility criteria. Four included a concomitant PARP inhibitor (either olaparib or veliparib) and paclitaxel, a neuropathy-causing chemotherapy agent; the remaining trial evaluated long-term monotherapy with olaparib. The pooled overall relative risk for the development of neuropathy with PARP inhibition was 1.06 (95% confidence interval: 1–1.4). Conclusions: PARP inhibition does not appear to reduce the risk of chemotherapy-induced peripheral neuropathy. Whether PARP inhibitors may palliate (rather than prevent) neuropathy remains an area in need of further investigation.

The commentary remarks on a recently published article on a study that examined predictors of poor outcomes in cancer patients using the SOFA score, answering to the question of whether the results of the study can completely inform decisions about terminal care management.

Background: Although 50% to 90% of patients who receive epidermal growth factor receptor (EGFR) inhibitors develop a rash, options for rash prevention or palliation remain limited. This issue is particularly important from a palliative care standpoint because these agents are prescribed only to patients with incurable cancer. Here, we report (1) gene expression profiling of skin biopsies from patients with an EGFR inhibitor–induced rash and (2) a randomized, placebo-controlled feasibility trial with the antiandrogen, spironolactone. Both investigations were undertaken to begin to explore the hypothesis that androgens mediate EGFR inhibitor–induced rash and that antiandrogens palliate it. Methods/Results: First, 4 skin biopsies from patients with EGFR inhibitor–induced rash (3 men and 1 woman) were subject to gene expression microarray profiling. A public data set of normal skin gene expression (Gene Expression Omnibus, GSE22998) served as a reference. Sixty percent of commonly interrogated androgen receptor genes (207 of 308 between the 2 data sets) were differentially expressed ( P < .05) in the rash samples. Second, in a 17-patient double-blinded, placebo-controlled trial with topical spironolactone applied to the face, although the primary feasibility end point was not achieved, patients in the spironolactone arm received more doses of EGFR inhibitor, and anecdotal photographic evidence suggested salutatory effects of spironolactone on rash. Conclusions: Epidermal growth factor receptor inhibitor–induced rash appears to be androgen-mediated; antiandrogen therapy merits further study for rash prevention/palliation.

End of life is difficult for all patients but sexual and gender minorities (SGM) are prone to isolation and loneliness, especially if their SGM status is unknown or unaccepted. In oncology clinics, where goals of care discussions about end of life are integral and frequent, querying patients about their SGM status and sexual health is of particular importance. The American Society of Clinical Oncology recently released a position statement that called for greater focus on SGM populations with the goal of reducing and eventually eliminating disparities in cancer care within this group. An important first step in addressing such disparities is learning how best to train cancer health-care providers to ask patients about their SGM status and about sexual health in general. This article summarizes the mandate for understanding cancer issues in SGM populations and the dearth of cancer-related data within this group. This article also describes an ongoing 3-part study intended to build a mini curriculum with the goal of helping cancer health-care providers to ask patients with cancer about SGM status and to ask all patients with cancer about sexual health issues. The results of this ongoing study could potentially improve end-of-life care for subgroups of patients.

Background Sexual and gender minority individuals face numerous cancer‐related inequities, many of which appear to be underreported. However, to the best of the authors’ knowledge, no one has assessed rates of acquisition of sexual orientation and gender identity (SOGI) data within community oncology settings. Methods Community oncology practices that were part of the NCI Community Oncology Research Program (NCORP) network were asked whether they routinely collected SOGI information and coded this information in their electronic medical records. The proportion of practice groups reporting routine collection of sexual and/or gender minority information was calculated. Potential associations between the collection of SOGI information and practice group–level and state‐level characteristics (from Gallup poll data) were also provided. Results Twenty‐four percent of the responding NCORP practice groups reported routine collection of sexual orientation information, and 10% reported collection of gender identity information. Practices located in western regions of the United States, practices in states with higher proportions of sexual and gender minority–identifying individuals, and practices with lower proportions of non‐Hispanic patients were more likely to ask patients about sexual orientation and/or gender identity. Conclusions US oncology practices that participate in research do not frequently collect SOGI information from patients with cancer. Educational initiatives should inform oncology staff and providers about the importance of collecting gender identity and sexual orientation information to improve existent disparities faced by sexual and gender minority patients.

Abstract Purpose A few previous studies report a direct relationship between older age and chemotherapy-induced neuropathy. This study further evaluated this adverse event's age-based risk. Methods CALGB 40101 investigated adjuvant paclitaxel (80 mg/m2 once per week or 175 mg/m2 every 2 weeks) in patients with breast cancer and served as a platform for the current study that investigated age-based differences in neuropathy. Grade 2 or worse neuropathy, as per Common Terminology Criteria for Adverse Events version 4, was the primary endpoint; patients were assessed at baseline, every 6 months for 2 years, and then annually for 15 years. Results Among these 1,881 patients, 230 were 65 years of age or older, 556 were 55–64 years, and 1,095 were younger than 55; 1,226 neuropathy events (commonly grade 1 or 2) were reported in 65% of the cohort. The number of grade 2 or worse events was 63 (27%), 155 (28%), and 266 (24%) within respective age groups (p = .14). In univariate analysis, only motor neuropathy had a higher age-based incidence: 19 (8%), 43 (8%), and 60 (5%), respectively (p = .04); in multivariate analyses, this association was no longer statistically significant. Other endpoints, such as time to onset of neuropathy (time from trial enrollment to neuropathy development) and time to improvement (time from maximal grade sensory neuropathy to a one-category improvement), showed no statistically significant age-based differences. In contrast, obesity was associated with neuropathy, and every 2-week paclitaxel was associated with trends toward neuropathy. Conclusion Although paclitaxel-induced neuropathy is common, older age is not an independent risk factor. Clinical trial identification number. NCT00041119 (CALGB 40101).