Extending venous thromboembolism secondary prevention with apixaban in cancer patients. The EVE trial.

BACKGROUND: Cancer-associated venous thromboembolism (VTE) management guideline recommendations include continued therapeutic anticoagulation while active cancer persists. The Federal Drug Administration label for apixaban for secondary VTE prevention includes a dose reduction to 2.5 mg twice daily after 6 months of treatment. OBJECTIVES: The study's purpose was to determine whether this dose reduction is advisable for cancer-associated VTE. METHODS: A randomized, double-blind trial compared apixaban 2.5 mg with 5 mg twice daily for 12 months among cancer patients with VTE who had completed 6 to 12 months of anticoagulation therapy. The primary outcome was combined major bleeding plus clinically relevant nonmajor bleeding. RESULTS: Of 370 patients recruited, 360 were included in the intention-to-treat analyses. Major plus clinically relevant nonmajor bleeding occurred in 16 of 179 patients (8.9%) in the apixaban 2.5 mg group compared with 22 of 181 patients (12.2%) in the 5 mg group (hazard ratio [HR], 0.72; 95% CI, 0.38-1.37; P = .39). Major bleeding occurred in 2.8% of the apixaban 2.5 mg group and in 2.2% of the 5 mg group (HR, 1.26; 95% CI, 0.34-4.66; P = .73). Recurrent VTE or arterial thrombosis occurred in 9 of 179 patients (5.0%) in the apixaban 2.5 mg group and 9 of 181 patients (5.0%) in the 5 mg group (HR, 1.0; 95% CI, 0.40-2.53; P = 1.00). All-cause mortality rates were similar between groups, 13% vs 12% (HR, 1.14; 95% CI, 0.63-2.04; P = .67). CONCLUSION: For secondary prevention of cancer-associated VTE, apixaban 2.5 mg compared with 5 mg twice daily did not lower combined bleeding events (EVE trial NCT03080883).

Statistical Considerations and Software for Designing Sequential, Multiple Assignment, Randomized Trials (SMART) with a Survival Final Endpoint.

Sequential, multiple assignment, randomized trial (SMART) designs are appropriate for comparing adaptive treatment interventions, in which intermediate outcomes (called tailoring variables) guide subsequent treatment decisions for individual patients. Within a SMART design, patients may be re-randomized to subsequent treatments following the outcomes of their intermediate assessments. In this paper, we provide an overview of statistical considerations necessary to design and implement a two-stage SMART design with a binary tailoring variable and a survival final endpoint. A chronic lymphocytic leukemia trial with a final endpoint of progression-free survival is used as an example for the simulations to assess how design parameters, including, choice of randomization ratios for each stage of randomization, and response rates of the tailoring variable affect the statistical power. We assess the choice of weights from restricted re-randomization on data analyses and appropriate hazard rate assumptions. Specifically, for a given first-stage therapy and prior to the tailoring variable assessment, we assume equal hazard rates for all patients randomized to a treatment arm. After the tailoring variable assessment, individual hazard rates are assumed for each intervention path. Simulation studies demonstrate that the response rate of the binary tailoring variable impacts power as it directly impacts the distribution of patients. We also confirm that when the first stage randomization is 1:1, it is not necessary to consider the first stage randomization ratio when applying the weights. We provide an R-shiny application for obtaining power for a given sample size for SMART designs.

The influence of anatomic stage and receptor status on first recurrence for breast cancer within 5 years (AFT-01).

BACKGROUND: Risk-stratified follow-up guidelines that account for the absolute risk and timing of recurrence may improve the quality and efficiency of breast cancer follow-up. The objective of this study was to assess the relationship of anatomic stage and receptor status with timing of the first recurrence for patients with local-regional breast cancer and generate risk-stratified follow-up recommendations. METHODS: The authors conducted a secondary analysis of 8007 patients with stage I-III breast cancer who enrolled in nine Alliance legacy clinical trials from 1997 to 2013 (ClinicalTrials.gov identifier NCT02171078). Patients who received standard-of-care therapy were included. Patients who were missing stage or receptor status were excluded. The primary outcome was days from the earliest treatment start date to the date of first recurrence. The primary explanatory variable was anatomic stage. The analysis was stratified by receptor type. Cox proportional-hazards regression models produced cumulative probabilities of recurrence. A dynamic programming algorithm approach was used to optimize the timing of follow-up intervals based on the timing of recurrence events. RESULTS: The time to first recurrence varied significantly between receptor types (p < .0001). Within each receptor type, stage influenced the time to recurrence (p < .0001). The risk of recurrence was highest and occurred earliest for estrogen receptor (ER)-negative/progesterone receptor (PR)-negative/Her2neu-negative tumors (stage III; 5-year probability of recurrence, 45.5%). The risk of recurrence was lower for ER-positive/PR-positive/Her2neu-positive tumors (stage III; 5-year probability of recurrence, 15.3%), with recurrences distributed over time. Model-generated follow-up recommendations by stage and receptor type were created. CONCLUSIONS: This study supports considering both anatomic stage and receptor status in follow-up recommendations. The implementation of risk-stratified guidelines based on these data has the potential to improve the quality and efficiency of follow-up.

Local/Regional Recurrence Rates After Breast-Conserving Therapy in Patients Enrolled in Legacy Trials of the Alliance for Clinical Trials in Oncology (AFT-01).

OBJECTIVE: We sought to evaluate local/regional recurrence rates after breast-conserving surgery in a cohort of patients enrolled in legacy trials of the Alliance for Clinical Trials in Oncology and to evaluate variation in recurrence rates by receptor subtype. BACKGROUND: Multiple randomized controlled trials have demonstrated equivalent survival between breast conservation and mastectomy, albeit with higher local/regional recurrence rates after breast conservation. However, absolute rates of local/regional recurrence have been declining with multi-modality treatment. METHODS: Data from 5 Alliance for Clinical Trials in Oncology legacy trials that enrolled women diagnosed with breast cancer between 1997 and 2010 were included. Women who underwent breast-conserving surgery and standard systemic therapies (n=4,404) were included. Five-year rates of local/regional recurrence were estimated from Kaplan-Meier curves. Patients were censored at the time of distant recurrence (if recorded as the first recurrence), death, or last follow-up. Multivariable Cox proportional hazards models were used to identify factors associated with time to local/regional recurrence, including patient age, tumor size, lymph node status, and receptor subtype. RESULTS: Overall 5-year recurrence was 4.6% (95% CI=4.0-5.4%). Five-year recurrence rates were lowest in those with ER+ or PR+ tumors (Her2+ 3.4% [95% CI 2.0-5.7%], Her2- 4.0% [95% CI 3.2-4.9%]) and highest in the triple-negative subtype (7.1% [95% CI 5.4-9.3%]). On multivariable analysis, increasing nodal involvement and triple-negative subtype were positively associated with recurrence ( P <0.0001). CONCLUSIONS: Rates of local/regional recurrence after breast conservation in women with breast cancer enrolled in legacy trials of the Alliance for Clinical Trials in Oncology are significantly lower than historic estimates. This data can better inform patient discussions and surgical decision-making.

"It's Like You Stuck a Pin in It:" African American/Black Patients Describe Cutaneous Toxicity From Epidermal Growth Factor Receptor Inhibitors.

Background: Epidermal growth factor receptor (EGFR) inhibitors cause cutaneous toxicity in over 90% of patients. Conceivably, healthcare providers could overlook such toxicity in African American/Black patients because of a darker complexion. This qualitative study sought to learn about such cutaneous signs and symptoms and, if present, to report them in patients' own words. Methods: Any patient who self-identified as African American/Black and who had been prescribed an EGFR inhibitor was eligible. The current report focuses on patients' responses to the following question, "What have you noticed since starting your cancer treatment (the EGFR inhibitor), any particular symptoms or reactions, positive or negative?" All interview data were audio-recorded, transcribed, and then independently coded and analyzed by two investigators. Results: Fifteen patients are the focus of this report, and all described cutaneous toxicity. Patients appeared troubled by the cosmetic aspect of these drug-induced skin changes, including their acneiform appearance, describing "little pimples with little, little pus in it." Notable were comments on hyperpigmentation, "I'm a black person but…. became darker." Furthermore, patients experienced physical symptoms: "it itches;" "it's like you stuck a pin in it;" "stinging;" and "burning;". Conclusion: Although cutaneous toxicity from EGFR inhibitors might be more difficult to visualize among darkly complected patients, the graphic descriptions offered in this qualitative study underscore the need for clinicians to heighten their awareness of such toxicity in African American/Black patients.

Clinical Trial Enrollment, Ineligibility, and Reasons for Decline in Older vs Younger Patients With Cancer in the National Cancer Institute Community Oncology Research Program.

This cross-sectional study assesses differences in clinical trial participation among older vs younger adults with cancer.

The Utility of Multistate Models: A Flexible Framework for Time-to-Event Data.

Purpose of Review: Survival analyses are common and essential in medical research. Most readers are familiar with Kaplan-Meier curves and Cox models; however, very few are familiar with multistate models. Although multistate models were introduced in 1965, they only recently receive more attention in the medical research community. The current review introduces common terminologies and quantities that can be estimated from multistate models. Examples from published literature are used to illustrate the utility of multistate models. Recent Findings: A figure of states and transitions is a useful depiction of a multistate model. Clinically meaningful quantities that can be estimated from a multistate model include the probability in a state at a given time, the average time in a state, and the expected number of visits to a state; all of which describe the absolute risks of an event. Relative risk can also be estimated using multistate hazard models. Summary: Multistate models provide a more general and flexible framework that extends beyond the Kaplan-Meier estimator and Cox models. Multistate models allow simultaneous analyses of multiple disease pathways to provide insights into the natural history of complex diseases. We strongly encourage the use of multistate models when analyzing time-to-event data. Supplementary Information: The online version contains supplementary material available at 10.1007/s40471-022-00291-y.

Hiccups in patients with cancer: a multi-site, single-institution study of etiology, severity, complications, interventions, and outcomes.

BACKGROUND: To our knowledge, previous studies have not investigated hiccups in patients with cancer with detailed patient-level data with the goal of capturing a broad spectrum of hiccup symptomatology. METHODS: This multi-site, single institution study examined consecutive medical records to better understand hiccups in patients with cancer. RESULTS: A total of 320 patients are the focus of this report. The median age of patients when hiccups were first reported in the medical record was 63 years (range: 21, 97 years) with 284 (89%) men and 36 (11%) women. The most common diagnose was gastrointestinal cancer. Hiccups most frequently occurred daily, as seen in 194 patients (62%), and the most common duration was less than 1 week, as seen in 146 patients (47%). However, nine patients had had daily hiccups for greater than 6 weeks, and 5 had symptoms for years. Cited etiology was non-chemotherapy medications in 36 (11%) and cancer chemotherapy in 19 (6%). Complications occurred in approximately a third and included insomnia in 51 patients (16%); hospitalization or emergency department visit in 34 (11%); and musculoskeletal pain in 23 (7%). Baclofen was the single most prescribed agent for hiccup palliation, but 100 patients received more than one medication. Medical procedures, which included acupuncture, paracentesis, or phrenic nerve block, were performed in 5 patients. In 234 patients (73%), the medical record documented hiccup cessation. CONCLUSIONS: Hiccups appear to be highly problematic in a small subset of patients with cancer with no well-defined palliative approaches.

Olanzapine for cisplatin-induced hiccups: observations from a 338-patient study.

BACKGROUND: Several case reports suggest that olanzapine palliates hiccups. To our knowledge, however, no larger scale studies have confirmed that olanzapine prevents or palliatives hiccups. Hence, the current study sought to substantiate the conclusions from these earlier case reports. METHODS: This multi-site single institution study focused on cisplatin-treated cancer patients because this chemotherapy agent is associated with hiccups and because olanzapine is often used as an antiemetic with this agent. Relevant data were extracted from medical records. Hiccup incidence shortly after chemotherapy was compared between olanzapine exposed and non-exposed patients. Other relevant variables were also assessed descriptively in an exploratory manner. RESULTS: A total of 338 patients were studied. One hundred forty-one had received olanzapine and 197 had not. Twenty-one (6%) developed hiccups. Eleven (8%) of these patients with hiccups had received olanzapine, and 10 (5%) had not [odds ratio (OR): 1.58; 95% confidence interval (CI): 0.65-3.83; P=0.31]. Of note, hiccups were more often observed in men 17 of 188 (9%) than in women 4 of 150 (3%) (OR: 3.64; 95% CI: 1.20-11.02; P=0.01). CONCLUSIONS: Despite previous case reports and despite the relatively low incidence of hiccups in this study, it does not appear olanzapine prevents or palliates hiccups. The study of other promising agents is warranted. Furthermore, this study invites caution in relying on single case reports in making clinical decisions.

Dexamethasone and hiccups: a 2000-patient, telephone-based study.

OBJECTIVES: Dexamethasone causes hiccups in an undefined percentage of patients, and these hiccups are often ignored ('My doctors just shook their heads like I was joking …'). This study sought to learn the percentage of dexamethasone-treated patients who develop hiccups and to explore patients' responses to the availability of educational materials on hiccups. METHODS: English-speaking, adult outpatients treated with oral, intravenous or epidural dexamethasone 2 weeks prior were contacted by phone and asked about hiccups. Educational materials were offered, and patients were queried on their opinion of the availability of such materials. RESULTS: One hundred and twenty-seven patients or 11% (95% CI 9% to 13%) reported hiccups. This percentage was derived from 1186 reachable patients from 2000 total patients. Fifty-four (43%) of those with hiccups desired to learn about educational materials. Of these, 49 completed a single-item, 5-point scale item: 21 (43%) viewed the availability of educational materials 'extremely helpful,' providing a 5 rating; 8 (16%) provided a 4; 4 (8%) provided a 3; and 1 (4%) provided a 2. CONCLUSIONS: Dexamethasone-induced hiccups occur in a small percentage of patients. The fact that most patients responded favourably to learning about the availability of educational materials suggests some have unmet needs.

Can older patients adopt and maintain a ketogenic diet? An observational study in support of clinical trials in older patients.

ABSTRACT: Ketogenic diets appear promising for obesity, diabetes, cancer, and other illnesses. Because older patients are more likely to contend with such illnesses and because of a paucity of dietary outcomes among these patients, we examined ketogenic diets in older patients.This multisite study focused on patients (≥65 years of age) on a ketogenic diet. Medical records were identified with the keywords "keto," "ketogenic," and "Atkins." Records were reviewed in detail with extraction of direct quotations to substantiate observations.We report on 200 consecutive patients with a median age of 70 years. Reasons for diet included weight loss, diabetes, and cancer; the majority remained on the diet for >1 month. In 134 (67%: 95% confidence interval: 60, 73%), the ketogenic diet appeared beneficial: 93 of 117 (79%) who sought weight loss lost weight ("She has lost 15 pounds and plans to lose another 8"); 36 of 67 (54%) who sought glucose control appeared to achieve the latter ("He has gone on a ketogenic diet and has been able to bring his sugars down significantly"); and 5 of 8 (63%) who sought improved cancer outcomes appeared to derive them ("He attributes part of the control of his cancer and increased QOL to adopting the keto for cancer diet"). Adverse events occurred in 30 patients (15%): dyslipidemia (n = 14), constipation (n = 9), sub-therapeutic international normalized ratio (n = 3), pancreatitis (n = 2), diarrhea (n = 1), and fatigue (n = 1).Trials that test ketogenic diets for a variety of illnesses should enroll older adults.

Observations with alpelisib in older patients (≥ 65 year of age) with breast cancer in a non-clinical trial setting.

PURPOSE: Alpelisib is newly-available breast cancer agent that targets PIK3 mutations and confers a somewhat unusual adverse event profile. This study focused on older patients (≥ 65 years of age) treated outside a clinical trial to gain further experience on how these under-studied patients do with this new agent. METHODS: This descriptive, multi-site study relied on medical record review. RESULTS: Fifty-one older breast cancer patients were started on alpelisib between May 2019 and September 2020. The median age and number of comorbidities at alpelisib initiation was 71 years and 4, respectively. Thirty-five patients had stopped alpelisib (median time on drug 2.6 months (range: < 1, 9.5 months)) for the following reasons: alpelisib adverse events (n = 15), cancer progression (n = 13), and other/unknown (n = 7). Alpelisib adverse events included hyperglycemia (n = 37), diarrhea (n = 23), rash (n = 19), fatigue (n = 12), and mouth sores (n = 7); (numbers in parentheses indicate the number of patients with at least one such event). Five patients were hospitalized for hyperglycemia. At the time of report, 14 patients were deceased, and median survival had not been reached. CONCLUSION: Older patients might derive further benefit from alpelisib if the adverse event profile of this agent, particularly the hyperglycemia, were able to be better managed.

How Did a Multi-Institutional Trial Show Feasibility of Electronic Data Capture in Older Patients With Cancer? Results From a Multi-Institutional Qualitative Study (Alliance A171902).

PURPOSE: New technology might pose problems for older patients with cancer. This study sought to understand how a trial in older patients with cancer (Alliance A171603) was successful in capturing electronic patient-reported data. METHODS: Study personnel were invited via e-mail to participate in semistructured phone interviews, which were audio-recorded and qualitatively analyzed. RESULTS: Twenty-four study personnel from the 10 sites were interviewed; three themes emerged. The first was that successful patient-reported electronic data capture shifted work toward patients and toward study personnel at the beginning of the study. One interviewee explained, "I mean it kind of lost all advantages…by being extremely laborious." Study personnel described how they ensured electronic devices were charged, wireless internet access was up and running, and login codes were available. The second theme was related to the first and dealt with data filtering. Study personnel described high involvement in data gathering; for example, one interviewee described, "I answered on the iPad, whatever they said. They didn't even want to use it at all." A third theme dealt with advantages of electronic data entry, such as prompt data availability at study completion. Surprisingly, some remarks described how electronic devices brought people together, "Some of the patients, you know, it just gave them a chance to kinda talk about, you know, what was going on." CONCLUSION: High rates of capture of patient-reported electronic data were viewed favorably but occurred in exchange for increased effort from patients and study personnel and in exchange for data that were not always patient-reported in the strictest sense.

Electronic Geriatric Assessment: Is It Feasible in a Multi-Institutional Study That Included a Notable Proportion of Older African American Patients? (Alliance A171603).

PURPOSE: This study determined whether an electronic version of the geriatric assessment is feasible in a multi-institutional, diverse setting. METHODS: Ten sites within the Alliance for Clinical Trials in Oncology participated. Patients who had active cancer or a history of cancer and were 65 years of age or older were eligible. The geriatric assessment was completed with an electronic data capture system that had been loaded onto iPads. Feasibility was defined a priori as completion in at least 70% of patients either with or without help. To enhance racial diversity, the original sample size was later changed and augmented by 50% with the intention of increasing enrollment of older minority patients. RESULTS: A total of one hundred fifty-four patients were registered with a median age of 72 years (range, 65-91 years). Forty-three (28%) identified themselves as African American or Black. One hundred forty-one patients (92%) completed the electronic geriatric assessment. Feasibility was observed across all subgroups, regardless of race, education, performance status, comorbidities, and cognition; 124 patients (81%) completed the geriatric assessment without help. Reasons for not completing the geriatric assessment are as follows: clinic visit did not occur (n = 6), no iPad connection to the Internet (n = 3), patient declined (n = 2), prolonged hospitalization (n = 1), and patient died (n = 1). Reasons for needing help, as reported by study personnel, were as follows: the patient preferred that research personnel ask the questions (n = 9), vision problem (n = 3), lack of comfort with the iPad (n = 2), questions were not clear (n = 1), less proficient in English (n = 1), and challenge in pressing the green button to go to the next question (n = 1). CONCLUSION: The electronic geriatric assessment is feasible in a multi-institutional setting that includes a notable proportion of African American or Black patients.

Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB Study.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially permanent adverse effect of chemotherapeutic agents including taxanes such as paclitaxel and platinum-based compounds such as oxaliplatin and carboplatin. Previous studies have suggested that genetics may impact the risk of CIPN. We conducted genome-wide association studies (GWASs) for CIPN in two independent populations who had completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-CIPN20 assessments (a CIPN-specific 20-item questionnaire which includes three scales that evaluate sensory, autonomic, and motor symptoms). The study population N08Cx included 692 participants from three clinical trials (North Central Cancer Treatment Group (NCCTG) N08C1, N08CA, and N08CB) who had been treated with paclitaxel, paclitaxel plus carboplatin, or oxaliplatin. The primary endpoint for the GWAS was the change from pre-chemotherapy CIPN20 sensory score to the worse score over the following 18 weeks. Study population The Mayo Clinic Breast Disease Registry (MCBDR) consisted of 381 Mayo Clinic Breast Disease Registry enrollees who had been treated with taxane or platinum-based chemotherapy. The primary endpoint for the GWAS assessed was the earliest CIPN20 sensory score available after the completion of chemotherapy. In multivariate model analyses, chemotherapy regimen (p = 3.0 × 10-8) and genetic ancestry (p = 0.007) were significantly associated with CIPN in the N08Cx population. Only age (p = 0.0004) was significantly associated with CIPN in the MCBDR population. The SNP most associated with CIPN was rs56360211 near PDE6C (p =7.92 × 10-8) in N08Cx and rs113807868 near TMEM150C in the MCBDR (p = 1.27 × 10-8). Due to a lack of replication, we cannot conclude that we identified any genetic predictors of CIPN.

Preemptive Versus Reactive Topical Clobetasol for Regorafenib-Induced Hand-Foot Reactions: A Preplanned Analysis of the ReDOS Trial.

BACKGROUND: Hand-foot skin reaction (HFSR) is the most common regorafenib-induced adverse event and is in need of effective prevention and palliation. MATERIALS AND METHODS: The Regorafenib Dose Optimization Study (ReDOS), a four-arm, previously published trial with a 1:1:1:1 randomization scheme, was analyzed in a manner in keeping with the original protocol to assess whether clobetasol 0.05% cream (a corticosteroid) applied to the palms and soles twice per day for 8 weeks was more effective when prescribed preemptively (before the development of HFSR) versus reactively (after the development of HFSR). Patients were assessed during the first two cycles of regorafenib. RESULTS: Sixty-one patients received preemptive clobetasol, and 55 received reactive clobetasol. Groups were balanced on demographics. Over the first two cycles, no evidence of HFSR occurred in 30% with preemptive clobetasol versus 13% with reactive clobetasol (p = .03). During the first cycle, 54% and 45% of patients had no HFSR with preemptive and reactive clobetasol, respectively (p = .35). During the second cycle, 33% and 15% had no HFSR with preemptive and reactive clobetasol, respectively (p = .02). During the second cycle, rates of grade 1, 2, and 3 HFSR were 30%, 8%, and 3%, respectively, with preemptive clobetasol and 43%, 18%, and 7%, respectively, with reactive clobetasol (p = .12). Patient-reported outcomes showed HFSR compromised nearly all activities of daily living with worse quality of life in patients who received reactive versus preemptive clobetasol. No clobetasol-induced adverse events were reported. CONCLUSION: Preemptive clobetasol might lessen regorafenib-induced hand-foot reactions compared with reactive therapy. Further confirmatory studies are needed in a larger patient cohort. IMPLICATIONS FOR PRACTICE: Regorafenib causes hand-foot skin reactions. Preemptive clobetasol, a high-potency topical corticosteroid, appears to lessen the severity of this adverse event. Although further study is needed, the favorable adverse event profile of this intervention might prompt clinicians to discuss this option with their patients.

Genetic Variations and Health-Related Quality of Life (HRQOL): A Genome-Wide Study Approach.

Health-related quality of life (HRQOL) is an important prognostic patient-reported outcome in oncology. Because prior studies suggest that HRQOL is, in part, heritable, we performed a GWAS to elucidate genetic factors associated with HRQOL in breast cancer survivors. Physical and mental HRQOL were measured via paper surveys that included the PROMIS-10 physical and mental health domain scales in 1442 breast cancer survivors participating in the Mayo Clinic Breast Disease Registry (MCBDR). In multivariable regression analyses, age and financial concerns were significantly associated with global physical health (age: p = 1.6 × 10-23; financial concerns: p = 4.8 × 10-40) and mental health (age: p = 3.5 × 10-7; financial concerns: p = 2.0 × 10-69). Chemotherapy was associated with worse global mental health (p = 0.01). In the GWAS, none of the SNPs reached the genome-wide association significance threshold of 5 × 10-8 for associations with either global physical or global mental health, however, a cluster of SNPs in SCN10A, particularly rs112718371, appeared to be linked to worse global physical health (p = 5.21 × 10-8). Additionally, SNPs in LMX1B, SGCD, PARP12 and SEMA5A were also moderately associated with worse physical and mental health (p < 10-6). These biologically plausible candidate SNPs warrant further study as possible predictors of HRQOL.

Toxicity and survival outcomes in older adults receiving concurrent or sequential chemoradiation for stage III non-small cell lung cancer in Alliance trials (Alliance A151812).

INTRODUCTION: Optimal treatment for older adults with stage III non-small cell lung cancer (NSCLC) remains unclear. Here we hypothesized that sequential chemoradiation therapy (sCRT) is better tolerated than concurrent (cCRT) but confers acceptable efficacy. We evaluated these strategies in older adults utilizing Alliance for Clinical Trials in Oncology data. MATERIALS AND METHODS: Pooled analyses from 6 first-line stage III NSCLC CRT trials (Cancer and Leukemia Group B 8433, 8831, 9130, 30106, 30407, 39801) were used to compare toxicity and survival outcomes with cCRT versus sCRT in patients age ≥ 65 years. Grade 3-5 adverse events (AEs), progression-free and overall survival (PFS; OS) are reported with adjustment for covariates. RESULTS: Four hundred older adults, of whom 106 (26.5%) had received sCRT and 294 (73.5%) had received cCRT, comprised the cohorts. Virtually all had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 (99%). More grade 3-5 AEs were observed at any time-point with cCRT than sCRT (94.2% versus 86.8%; 95% confidence interval for difference in proportions, 1.3%, 15.5%) and this finding remained after adjusting for length of study treatment (P = 0.018). Comparable PFS and OS were observed with sCRT versus cCRT (median: 8.0 versus 9.2 months; median: 11.9 versus 13.4 months, respectively) even after adjustment for age, sex, ECOG PS, body mass index, pretreatment weight loss, stage, and cisplatin-based therapy (P = 0.604 and P = 0.906, respectively). DISCUSSION: These data show that sCRT was associated with less toxicity than cCRT with no associated statistically significant decrease in efficacy outcomes and that sCRT merits further study in this population.