A Cohort Study to Evaluate Genetic Predictors for Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS): Results from ECOG-ACRIN E1Z11.

PURPOSE: Aromatase Inhibitor-Associated Musculoskeletal Symptoms (AIMSS) are common and frequently lead to AI discontinuation. Single nucleotide polymorphisms (SNPs) in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate associations between 10 SNPs and AI discontinuation due to AIMSS. PATIENTS AND METHODS: Postmenopausal women with stage I-III hormone receptor-positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcomes (PRO) to assess AIMSS (Stanford Health Assessment Questionnaire; HAQ) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS, and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial strata provided 80% power to detect an effect size of 1.5-4. SNPs were in ESR1 (rs2234693, rs2347868, rs9340835), CYP19A1 (rs1062033, rs4646), TCL1A (rs11849538, rs2369049, rs7158782, rs7159713), and HTR2A (rs2296972). RESULTS: Of 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. While more Black and Asian women developed AIMSS compared to White women (49% vs 39%, p=0.017; 50% vs 39%, p=0.004, respectively), AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population, or in distinct cohorts. The odds ratio for rs2296972 (HTR2A) approached significance for developing AIMSS. CONCLUSION: We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, PRO predictors of AIMSS, and differences by race.

Body composition measurements and clinical outcomes in patients with resectable pancreatic adenocarcinoma - analysis from SWOG S1505.

BACKGROUND: Sarcopenic obesity and muscle attenuation have been associated with survival in patients with borderline resectable and advanced pancreatic ductal adenocarcinoma (PDA); however, these relationships are unknown for patients with resectable PDA. This study examined the associations between skeletal muscle and adipose tissue as measured on baseline computed tomography (CT) and the overall survival (OS) of participants with resectable PDA in a secondary analysis of the Southwest Oncology Group S1505 clinical trial (identifier: NCT02562716). METHODS: The S1505 phase II clinical trial enrolled patients with resectable PDA who were randomized to receive modified FOLFIRINOX or gemcitabine and nab-paclitaxel as perioperative chemotherapy, followed by surgical resection. Baseline axial CT images at the L3 level were analyzed with externally validated software, and measurements were recorded for skeletal muscle area and skeletal muscle density, visceral adipose tissue area (VATA) and density, and subcutaneous adipose tissue area and density. The relationships between CT metrics and OS were analyzed using Cox regression models, with adjustment for baseline participant characteristics. RESULTS: Of 98 eligible participants with available baseline abdominal CT, 8 were excluded because of imaging quality (eg, orthopedic hardware), resulting in 90 evaluable cases: 51 men (57.0%; mean age, 63.2 years [SD, 8.5]; mean body mass index [BMI], 29.3 kg/m2 [SD, 6.4]), 80 White (89.0%), 6 Black (7.0%), and 4 unknown race (4.0%). Sarcopenia was present in 32 participants (35.9%), and sarcopenic obesity was present in 10 participants (11.2%). Univariable analyses for the 6 variables of interest indicated that the standardized mean difference (hazard ratio [HR], 0.75; 95% CI, 0.57-0.98; P = .04) was statistically significantly associated with OS. In models adjusted for sex, race, age, BMI, performance score, contrast use, sarcopenia, and sarcopenic obesity, VATA was statistically significantly associated with OS (HR, 1.58; 95% CI, 1.00-2.51; P = .05). No difference was observed in OS between participants according to sarcopenic obesity or sarcopenia categories. The median OS estimates were 25.1 months for participants without sarcopenic obesity, 18.6 months for participants with sarcopenic obesity, 23.6 months for participants without sarcopenia, and 27.9 months for participants with sarcopenia. CONCLUSION: This was the first study to systematically evaluate body composition parameters in a prospective multicenter trial of patients with resectable PDA who received perioperative chemotherapy. Visceral adipose tissue was associated with survival; however, there was no association between OS and sarcopenia or sarcopenic obesity. Further studies should evaluate these findings in more detail.

Clinician perceptions of care difficulty, quality of life, and symptom reports for lung cancer patients: an analysis from the Symptom Outcomes and Practice patterns (SOAPP) study.

INTRODUCTION: Despite recent therapeutic advances, lung cancer is a difficult disease to manage. This study assessed clinicians' perceptions of care difficulty, quality of life (QOL), and symptom reports for their lung cancer patients compared with their patients with breast, prostate, and colon cancer. METHODS: This report focused on secondary analyses from the Eastern Cooperative Oncology Group (ECOG) Symptom Outcomes and Practice Patterns (SOAPP) study (E2Z02); outcome measures included clinician ratings of 3106 solid tumor patients. Univariate analyses focused on patterns of disease-specific perceptions; multivariable analyses examined whether disease-specific differences persisted after covariate inclusion. RESULTS: In univariate comparisons, clinicians rated lung cancer patients as more difficult to treat than other solid tumor patients, with poorer QOL and higher symptom reports. After covariates were adjusted, the odds of clinicians perceiving lower QOL for their lung cancer patients were 3.6 times larger than for patients with other solid tumors (odds ratio = 3.6 [95% confidence interval, 2.0-6.6]; p < 0.0001). In addition, the odds of clinicians perceiving weight difficulties for their lung cancer patients were 3.2 times larger (odds ratio = 3.2 [95% confidence interval, 1.7-6.0]; p = 0.0004). No other outcome showed significant differences between lung versus other cancers in multivariable models. CONCLUSION: Clinicians were more pessimistic about the well-being of their lung cancer patients compared with patients with other solid tumors. Differences remained for clinician perceptions of patient QOL and weight difficulty, even after controlling for such variables as stage, performance status, and patient-reported outcomes. These continuing disparities suggest possible perception bias. More research is needed to confirm this disparity and explore the underpinnings.