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ImportanceFor many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes.ObjectiveTo analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT).Design, Setting, and ParticipantsThis study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute–sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023.ExposuresTreatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy.Main Outcomes and MeasuresThe outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable.ResultsThe analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; P = .04). The HR for OS was 1.33, but the results were not statistically significant (95% CI, 0.99-1.77; P = .05). Radiotherapy duration longer than 39 days (vs ≤39 days) was associated with a higher risk of LRF (HR, 1.32; 95% CI, 1.06-1.65; P = .01). As a continuous variable, RT duration (per 1 week increase) was associated with DFS failure (HR, 1.14; 95% CI, 1.01-1.28; P = .03). The HR for LRF 1.13, but the result was not statistically significant (95% CI, 0.99-1.28; P = .07).Conclusions and RelevanceResults of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes.

Chemotherapy-induced peripheral neuropathy (henceforth, neuropathy) is often dose limiting and is generally managed by empirical dose modifications. We aimed to (1) identify an early time point that is predictive of future neuropathy using a patient-reported outcome and (2) propose a dose-adjustment algorithm based on simulated data to manage neuropathy. In previous work, a dose-neuropathy model was developed using dosing and patient-reported outcome data from Cancer and Leukemia Group B 40502 (Alliance), a randomized phase III trial of paclitaxel, nanoparticle albumin-bound paclitaxel or ixabepilone as first-line chemotherapy for locally recurrent or metastatic breast cancer. In the current work, an early time point that is predictive of the future severity of neuropathy was identified based on predictive accuracy of the model. Using the early data and model parameters, simulations were conducted to propose a dose-adjustment algorithm for the prospective management of neuropathy in individual patients. The end of the first 3 cycles (12 weeks) was identified as the early time point based on a predictive accuracy of 75% for the neuropathy score after 6 cycles. For paclitaxel, nanoparticle albumin-bound paclitaxel, and ixabepilone, simulations with the proposed dose-adjustment algorithm resulted in 61%, 48%, and 35% fewer patients, respectively, with neuropathy score ≥8 after 6 cycles compared to no dose adjustment. We conclude that early patient-reported outcome data on neuropathy can be used to guide dose adjustments in individual patients that reduce the severity of future neuropathy. Prospective validation of this approach should be undertaken in future studies.

We tested whether a low-literacy-friendly, multimedia information and assessment system used in daily clinical practice enhanced patient-centered care and improved patient outcomes. This was a prospective, parallel-group, randomized controlled trial with 2 arms, CancerHelp-Talking Touchscreen (CancerHelp-TT) versus control, among adults with Stage I–III breast or colorectal cancer receiving chemotherapy and/or radiation therapy in safety net settings. Each patient was assessed for outcomes at 4 timepoints: after starting treatment (baseline), during treatment, immediately after treatment, and at follow-up assessment. The primary outcomes were health beliefs, cancer knowledge, self-efficacy, and satisfaction with communication about cancer and its treatments. Health-related quality of life (HRQOL) was a secondary outcome. A total of 129 patients participated in the study (65 intervention and 64 control), and approximately 50% of these completed the study. Patients randomized to receive the CancerHelp-TT program had a significantly larger increase in their cancer knowledge in comparison to those randomized to the control arm (effect size = .48, P = .05). While effect sizes for differences between randomized groups in self-efficacy, health beliefs, HRQOL, and satisfaction with communication were small (.10–.48), there was a consistent trend that participants in the intervention group showed larger increases over time in all outcomes compared to the control group. The CancerHelp-TT software was favorably rated by intervention participants. The CancerHelp-TT program showed promise to increase vulnerable cancer patients’ cancer knowledge and adaptive health beliefs and attitudes. However, vulnerable patients may need additional interventional support in settings outside cancer clinics.

10541 Background: It is well known that estrogen exposure is a major risk factor for breast cancer (BC). Estrogen levels can be affected by the gut microbiome through enterohepatic circulation. No studies regarding gut microbiome changes in BC have examined the colonic mucosal microbiome; and there is no data on which types of gut microbiome studies would be most relevant to the study of the microbiome in BC. Methods: We examined differences in the gut microbiome composition in BC and control subjects using the following sample types: Home-collected stool, endoscopically collected stool, and colonic biopsy samples (for all groups, n=48 total, n=24 BC, n=24 controls). Here, we used both operational taxonomic unit (OTU) and amplicon sequence variant (ASV) based approaches in QIIME2 for 16S rDNA sequencing analysis. Alpha diversity metrics (Chao1, Pielou’s Evenness, Faith PD, Shannon, and Simpson) and beta diversity metrics (Bray-Curtis, Weighted and Unweighted Unifrac) were calculated. LefSe was used to analyze differences in the abundance of various taxa between sample types. Results: Alpha and beta diversity metrics were different between the three sample types when using both OTU or ASV-based analysis, however there were some minor differences between analysis types in these samples. Comparing the 3 sample types, Actinobacteria and Firmicutes (Log10 LDA score >4) were the predominant phyla in home stool samples, while Bacteroidetes and Proteobacteria (Log10 LDA score >4) were higher in abundance in the colonic biopsy samples. Conclusions: Our data shows that alpha and beta diversity metrics differ between sampling methods (home-collected stool, endoscopically collected stool, and colonic biopsies) when looking at the composition of the gut microbiome in BC. Results remained the same regardless of ASV or OTU-based analysis. [Table: see text]

Background The Adjuvant Zoledronic Acid (ZA) study in early breast cancer (AZURE) showed correlation between a non-amplified MAF gene in the primary tumor and benefit from adjuvant zoledronic acid (ZA). Adverse ZA outcomes occurred in MAF-amplified patients. NSABP B-34 is a validation study. Methods A retrospective analysis of MAF gene status in NSABP B-34 was performed. Eligible patients were randomly assigned to standard adjuvant systemic treatment plus 3-years oral clodronate (1600mg/daily) or placebo. Tumors were tested for MAF gene amplification, and analyzed for their relationship to clodronate for disease-free survival (DFS) and overall survival (OS) in MAF non-amplified patients. All statistical tests were 2-sided. Results . MAF status was assessed in 2,533 available primary tumor samples from 3,311 patients. Of these, 37 withdrew consent; in 77 samples no tumor was found; 536 assays did not meet quality standards, leaving 1,883 (77.8%) evaluable for MAF assay by fluorescence in situ hybridization (947 from placebo, and 936 from clodronate arms). At 5 years, in MAF non-amplified patients receiving clodronate, DFS improved by 30% (hazard ratio =0.70, 95% confidence interval = 0.51-0.94, P=0.02). OS improved at 5 years (hazard ratio =0.59, 95% confidence interval = 0.37–0.93, P=0.02) remaining statistically significant for clodronate throughout study follow-up. Conversely, adjuvant clodronate in women with MAF-amplified tumors was not associated with benefit, but possible harm in some subgroups. Association between MAF status and menopausal status was not seen. Conclusions Non-amplified MAF showed statistically significant benefits (DFS and OS) with oral clodronate, supporting validation of the AZURE study.

Background Upfront docetaxel (UD) with androgen deprivation therapy (ADT) has been demonstrated to improve survival outcomes in metastatic castration-sensitive prostate cancer (mCSPC). However, existing studies have included predominantly Caucasian patients. Study question To compare the efficacy of addition of UD to ADT in mCSPC to ADT alone among minority patients. Study design Retrospective study of mCSPC patients. Measures and outcomes Patients treated with UD and ADT between January 2014 and December 2017 (UD + ADT, n = 44) were compared with those treated with ADT alone between January 2008 and January 2017 (ADT, n = 38); patients of Caucasian ethnicity were excluded. The outcome of interest was progression-free survival (PFS), which was estimated using Kaplan-Meier analysis and Cox proportional hazard analysis. Results Overall, 63 (76.8%) patients were African American and 16 (19.5%) were Hispanic. Fifty-five (67%) patients had high-volume mCSPC. The median follow-up was 14 months [95% confidence interval (CI): 10.4-16.5] for UD + ADT and 42 months (95% CI: 17-66.9) for ADT. Median PFS did not differ between groups: UD + ADT: 16 versus ADT: 18 months [hazard ratio (HR) for UD + ADT = 0.88, 95% CI: 0.48-1.62; P = 0.70]. In patients with high-volume disease, median PFS remained similar (UD + ADT: 16 vs. ADT: 14 months (HR for UD + ADT = 0.64, 95% CI: 0.33-1.25; P = 0.19). On multivariable analysis, prolonged time to nadir PSA, HR = 0.83 (95% CI: 0.76-0.90), was independently associated with PFS. The most common toxicities in UD + ADT were anemia and fatigue. Major limitations include small sample size and potential for selection bias due to the retrospective study design. Conclusions In this retrospective review of a minority mCSPC cohort, UD + ADT was not associated with improved PFS compared with ADT alone. Although further study with larger sample size is needed, these results underscore the importance of ensuring accrual of minorities in clinical trials, reflective of the real-world setting.

PURPOSE: The aim of this study was to elucidate the prevalence of unmet supportive care needs in Hispanic/Latino cancer survivors and examine the association between unmet needs and patient-provider communication, satisfaction with cancer care, and cancer-specific symptom burden. METHODS: Hispanics/Latinos diagnosed with breast, prostate, or colorectal cancer within 15 months of treatment completion (N=288) completed questionnaires as part of an NCI-funded project. RESULTS: Hispanic/Latino cancer survivors reported greater unmet needs compared to previously published norms in primarily non-Hispanic/Latino white samples. Across the three cancer types, the two most common unmet needs were in the psychological domain: fear of metastasis (32.6%) and concern for close others (31.3%). However, unmet needs varied by cancer type. Factors associated with greater unmet needs included more recent cancer diagnosis (OR .98 [.96-.99]), younger age (OR .96-.97 [.93-.99]), female gender (OR 2.53–3.75 [1.53–7.36]), and being single (OR 1.82 [1.11–2.97]). Breast cancer survivors reported greater unmet needs than both prostate and colorectal cancer survivors (OR 2.33–5.86 [1.27–14.01]). Adjusting for sociodemographic and medical covariates, unmet needs were associated with lower patient-provider communication self-efficacy (B= −.18– −.22, p’s < .01) and satisfaction with cancer care (B= −2.05– −3.81, p’s < .05), and greater breast (B= −4.18– −8.30, p’s < .01) and prostate (B= −6.01– −8.13, p’s < .01) cancer-specific symptom burden. CONCLUSIONS: Findings document unmet supportive care needs in Hispanic/Latino cancer survivors and suggest that reducing unmet needs in Hispanic/Latino cancer survivors may improve not only satisfaction with care, but also health-related quality of life.

BACKGROUND The objective of the current study was to examine how modifiable factors such as satisfaction with cancer care and self-efficacy impact health-related quality of life (HRQOL) among Latino cancer survivors. METHODS Latinos previously diagnosed with breast, prostate, or colorectal cancer (N = 288) completed questionnaires (Patient Satisfaction with Cancer Care Scale, Stanford Chronic Disease Self-Management Measures, Functional Assessment of Cancer Therapy-General, and Short Acculturation Scale for Hispanics) within 2 years after receiving primary cancer treatment. RESULTS Path model analyses demonstrated that satisfaction with cancer care was associated with greater HRQOL and that this relationship was explained by several facets of self-efficacy (ie, confidence in managing psychological distress [z = 3.81; P

Objectives: To identify areas for improvement and design system-based strategies to address challenges in the provision of quality ovarian cancer care, we undertook a quality improvement (QI) program at 2 large US-based hospital systems. Methods: At baseline, between 9/2019 and 2/2020, we audited 200 EMR records (100 from each system) of adult patients with recurrent ovarian cancer for assessing physicians’ performance of quality-based and National Comprehensive Cancer Network (NCCN) guideline-directed biomarker testing, maintenance treatment, monitoring, and patient-centered practices. Multidisciplinary ovarian cancer teams in each center participated in QI interventions including feedback on baseline EMR results and development of action plans. Post-intervention, 200 additional recurrent ovarian cancer patient EMRs were retrospectively reviewed in each center between 2/2020 and 9/2020 to determine the effect of the intervention on ovarian cancer care. Results: At baseline, for 200 patients diagnosed with ovarian cancer who's EMR were audited, the mean age was 66 years and the average time since diagnosis was 3 years. In these patients, documentation of BRCA1/2 testing, use of maintenance therapy, patient follow-up, and shared decision-making (SDM) were sub-optimal (Table). Action plans, such as development of resources for guidance with regard to therapy sequencing and patient management strategies, development of a new adverse event management plan, and improvements in documentation and care coordination procedures, were implemented. In the post-intervention EMR audits, 200 patient's demographics were similar to baseline: the mean age was 62 years and the average time since diagnosis was 3 years. At follow-up, EMR audits demonstrated a significant 46% improvement in BRCA1/2 testing (P Download : Download high-res image (67KB) Download : Download full-size image Conclusions: These results demonstrate that aligning care with guidelines can be challenging; however, implementation of system- and team-based interventions can lead to improved documentation of care practices. These methods and findings from this program are relevant for the future design of intervention to improve the quality of recurrent ovarian cancer care.

e18649 Background: Molecular biomarker testing is integral to NSCLC cancer care, but adoption and testing practices in the community are varied and often suboptimal. Testing practices, such as standard testing protocols and results turnaround time (TAT), impact timely treatment decisions. We examined adoption and testing practices for guideline recommended NSCLC biomarkers among National Cancer Institute Community Research Program (NCORP) sites. The study was conducted in collaboration with Wake Forest NCORP Research Base. Methods: An online survey was administered to onsite labs affiliated with NCORP sites April 2019 – June 2020. We assessed testing practices for 7 NCCN recommended biomarkers, including 3 with category 1 recommendation (EGFR, ALK, PD-L1) and 4 with category 2 recommendations (BRAF, ROS1, MET, RET). Guideline concordant result TAT was defined as return of EGFR and ALK results in ≤ 10 days (Lindeman 2018) (see Table for other outcomes). We used proportions, including two-sided Fischer exact tests, to compare outcomes by site characteristics (safety net, practice size). Results: The survey response rate was 69% (58/85). All responding labs offered testing for category 1 biomarkers (EGFR, ALK and PD-L1); only 10% conducted these tests in-house (Table). The majority of labs also tested for category 2 biomarkers (67%). TAT varied, with most labs returning results in ≤ 10 days for EGFR and ALK (69%, but only a minority meet this TAT for all biomarkers. Larger practice size (> 1400 new cancer cases a year) was associated with in-house testing of EGFR, ALK, PD-L1 (p=0.03) and having standard testing protocols (p

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity caused by several chemotherapeutic agents. Currently, CIPN is managed by empirical dose modifications at the discretion of the treating physician. The goal of this research is to quantitate the dose-CIPN relationship to inform the optimal strategies for dose modification. Data were obtained from the Cancer and Leukemia Group B (CALGB) 40502 trial, a randomized phase III trial of paclitaxel vs. nab-paclitaxel vs. ixabepilone as first-line chemotherapy for locally recurrent or metastatic breast cancer. CIPN was measured using a subset of the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group Neurotoxicity (FACT-GOG-NTX) scale. A kinetic-pharmacodynamic (K-PD) model was utilized to quantitate the dose-CIPN relationship simultaneously for the three drugs. Indirect response models with linear and Smax drug effects were evaluated. The model was evaluated by comparing the predicted proportion of patients with CIPN (score ≥8 or score ≥12) to the observed proportion. An indirect response model with linear drug effect was able to describe the longitudinal CIPN data reasonably well. The proportion of patients that were falsely predicted to have CIPN or were falsely predicted not to have CIPN was 20% or less at any cycle. The model will be utilized to identify an early time point that can predict CIPN at later time points. This strategy will be utilized to inform dose adjustments to prospectively manage CIPN. Clinicaltrials.gov ID: NCT00785291

Lung cancer patients experience multiple, simultaneous symptoms related to their disease and treatment that impair functioning and health-related quality of life (HRQL). Computer technology can reduce barriers to nonsystematic, infrequent symptom assessment and potentially contribute to improved patient care.To evaluate the efficacy of technology-based symptom monitoring and reporting in reducing symptom burden in patients with advanced lung cancer.This was a prospective, multisite, randomized controlled trial. Two hundred fifty-three patients were enrolled at three sites and randomized to monitoring and reporting (MR) or monitoring alone (MA). Patients completed questionnaires at baseline, 3, 6, 9, and 12 weeks and symptom surveys via interactive voice response weekly for 12 weeks. MR patients' clinically significant symptom scores generated an e-mail alert to the site nurse for management. The primary endpoint was overall symptom burden; secondary endpoints included HRQL, treatment satisfaction, symptom management barriers, and self-efficacy.This randomized controlled trial failed to demonstrate efficacy of symptom monitoring and reporting in reducing symptom burden compared with monitoring alone in lung cancer. HRQL declined over 12 weeks in both groups (P 0.006 to P 0.025); at week 12, treatment satisfaction was higher in MA than MR patients (P 0.012, P 0.027). Adherence to weekly calls was good (82%) and patient satisfaction was high.Feasibility of using a technology-based system for systematic symptom monitoring in advanced lung cancer patients was demonstrated. Future research should focus on identifying patients most likely to benefit and other patient, provider, and health system factors likely to contribute to the system's success.

Background Capecitabine is an oral fluoropyrimidine that is used to treat various malignancies. Hand-foot syndrome (HFS) is a dose-limiting toxicity of capecitabine that can limit the use of this agent in some patients. Some investigators have observed that pyridoxine (vitamin B6) can ameliorate HFS that is caused by capecitabine. We designed a prospective trial to determine if pyridoxine can prevent HFS in patients who receive capecitabine. Methods In our double-blind, placebo-controlled trial, we randomly assigned eligible patients who were treated with capecitabine to receive either daily pyridoxine 100 mg or placebo along with their capecitabine-containing chemotherapy regimen. Patients were observed during the first 4 cycles of capecitabine treatment. The primary endpoint was the incidence and grade of HFS that occurred in both study arms. Results Between 2008 and 2011, 77 patients were randomly assigned to receive either pyridoxine (n = 38) or placebo (n = 39). Dosages of capecitabine were equally matched between both arms of the study. HFS occurred after a median of 2 chemotherapy cycles in both groups. HFS developed in 10 of 38 (26%) patients in the pyridoxine group and in 8 of 39 (21%) patients in the placebo group (P = .547). Therefore, the risk of HFS was 5 percentage points higher in pyridoxine group (95% confdence interval [CI] for difference, -13 percentage points to +25 percentage points). Given our study results, a true benefit from pyridoxine can be excluded. No difference in HFS grades was observed. Limitations Single-institution study. Conclusion Prophylactic pyridoxine (vitamin B6), given concomitantly with capecitabine-containing chemotherapy, was not effective for the prevention of HFS.

e14134 Background: Immune-related endocrine dysfunction is unique to immunotherapy (IT). We aimed to explore the clinical parameters associated with development of thyroid disorder (TD) in patients receiving IT and their outcome. Methods: We designed a retrospective study of patients treated with anti-CTLA4 and/or anti-PD1/PDL1 IT at Cook County Hospital, Chicago between January 2015 to January 2018. Patients with incomplete charts and those who received less than two cycles of IT were excluded. Demographics, clinical and pathologic data were recorded at the time of diagnosis and prior to start of IT. Pearson Chi-square, independent sample t-test and logistic regression were used for data analysis. Results: We included 104 patients in the study, out of whom 66 were male and 38 were female. Most common diagnosis was non-small cell lung cancer (42.4%) followed by squamous cell cancer of head and neck (21.2%), renal cell cancer (12.5%), small cell lung cancer (12.5%) and melanoma (8.7%). Majority of patients (91.4%) had metastasized and were treated with either Nivolumab (71.1%) or Pembrolizumab (21.2%) in the 2nd (50%) or 3rd line (29.8%) setting. Twenty-eight patients developed TD while on IT, out of whom, 13 developed hypothyroidism, 12 developed hyperthyroidism followed by hypothyroidism and 3 developed hyperthyroidism. TD developed between 1st to 6th cycle of IT in 96.5% patients. Older age (p-0.009), history of radiation (RT) to neck (p-0.007), history of RT to chest (p-0.015), history of venous thrombosis (p-0.007) and higher thyroid stimulating hormone (TSH) level (17.76±35.67) prior to starting IT (p-0.029) were significantly associated with TD. Multivariate logistic regression showed that history of RT to neck was a significant predictor of developing TD after adjustment for age, race and sex (adjusted OR 9.64, 95% CI 1.88-49.36, p-0.007). No patient reported thyroid related symptom and IT was continued uninterrupted in all patients. Levothyroxine was the drug of choice for treating hypothyroidism. No patient received steroids or antithyroid medications. Conclusions: History of radiation therapy to neck is significantly associated with development of thyroid dysfunction in patients receiving immunotherapy. Thyroid replacement therapy is sufficient to bring down the levels of TSH and immunotherapy need not be interrupted.

e12093 Background: The Recurrence Score (RS) result based on the 21-gene Oncotype DX Breast Recurrence Score assay is standard of care in deciding adjuvant chemo-hormonal therapy versus hormone therapy alone in hormone-receptor positive (HR+), HER 2 negative, node–negative breast cancer. This study explores the role of RS result in predicting the response to neoadjuvant chemotherapy (NACT). Methods: In this retrospective single institution cohort study, electronic medical records of 148 women with HR+, HER 2 negative, non-metastatic breast cancer who received NACT from 2006 onward were screened. 38 patients were excluded due to lack of tissue for testing. Pretreatment biopsy blocks were sent to Genomic Health, Inc. for Oncotype Dx testing. Low RS result was defined as ≤25. Pathologic complete response (pCR) was defined as no residual tumor. Partial response (PR) was residual tumor with > 25% decrease in the largest dimension. No response (NR) was defined as < 25% decrease in the tumor post NACT. Progression (PD) was defined as increase in size of original tumor or new site(s) of disease. Results: Of the 110 patients studied, 58% were postmenopausal women. Fifty percent were African American, 12% were Caucasian and 27% were Hispanic. Invasive ductal carcinoma was the predominant histology (86%). Most patients had > T2 disease (97%) with 73% being clinically node positive. Adriamycin based NACT regimen was used in treating 86.3% of the women. Forty patients (36.4%) had tumor with RS≤25. NR/PD was significantly higher in tumors with RS≤25 (27/40) vs RS > 25 (13/70) (OR: 9.1, 95% CI: 3.7-22.2, P< 0.001). pCR was seen in 16% with RS > 25 and 0% with RS ≤25. Response to NACT (pCR/PR) was 32.5% in RS≤25 vs 81.4% in RS > 25. In tumors with response, RS > 25 was associated with a greater percent decrease in the tumor size compared to RS≤25 (median decrease of 71% vs 52%, P= 0.033). Conclusions: HR+, HER 2 negative, RS≤25 breast cancer is associated with increased rates of NR/PD and is unlikely to respond to NACT. Recurrence Score result determination in pretreatment breast cancer biopsy samples can be an effective tool to select patients with non-metastatic breast cancer for NACT. Studies are needed to determine novel neoadjuvant therapeutic approaches in patients who are candidates for neoadjuvant therapy but are unlikely to benefit from NACT.

525 Background: Exposure to cytotoxic chemotherapy (CC) has been observed to be associated with significant changes in body composition, namely marked lean muscle mass losses, with implications for treatment-related toxicity and oncologic outcomes. However, prior studies predominately include elderly patients who, a priori, are at risk for sarcopenia or severe skeletal muscle deficiency. To date, the impact of CC on body composition in young men with testicular cancer remains undefined. Methods: A retrospective analysis of 19 patients with metastatic testicular cancer treated with CC was performed (2015-17). Lumbar skeletal muscle index (SMI), visceral (VAI), subcutaneous (SCAI), and intramuscular adipose (IMAI) indices (cm2/m2), as well as fat-free mass (FFM, kg) and fat mass (FM, kg) were calculated using cross-sectional soft tissue area measurements on pre- and post-CC computed tomography (CT) axial scans and compared using paired Wilcoxon Signed Rank Tests. Results: Median age was 29 years. According to the NHANES FMI-based classification, 5 (26.3%), 9 (47.4%), 4 (21.1%), and 1 (5.3%) patients had normal, excess, class I, and class II obesity, respectively. Median pre- and post-CC BMI was 27.7 vs. 29.6 kg/m2(p = 0.03). Median pre- and post-CC SMI, VAI, SAI, and IAI were 63.5 vs 57.8 (p = 0.14), 19.9 vs 30.8 (p = 0.01), 47.9 vs 58.2 (p = 0.03), and 3.0 vs 5.2 (p = 0.002), respectively. Median muscle density pre- and post-CC were 47.0 vs 43.6 HU (p = 0.002). Pre- and post-chemotherapy FFM were 21.5 vs 19.5 kg, representing an overall median loss of 2.8%, (IQR -10.1, +4.7; Range -49.5 - +16.3; p = 0.14). Conversely, pre- and post-CC FM were 6.6 vs 7.5 kg, representing an overall median gain of 13.3% (IQR -3.3, +17.0; -24.9 - +50; p = 0.01). Median time between imaging assessments was 121 days. Specific median measures of adiposity each increased significantly, such that VIA increased by 29% (p = 0.01), SCAI increased by 39.7% (p = 0.03), and IMIA increased by 39.7% (p = 0.002). Conclusions: While lean muscularity remained stable, we observed significant increases in total body adipose mass with decreased muscle density in this consecutive case series of testicular cancer patients following CC.

Erlotinib is one of the most widely used tyrosine kinase inhibitor targeting human epidermal growth factor receptor. Since its introduction, it has revolutionized the treatment of advanced non-small cell lung cancer. Skin rashes and diarrhea are the most often reported side effects of erlotinib however it is also associated with interstitial pneumonitis or interstitial lung disease, which often turns out to be fatal complication of using this medicine. Though reported scarcely in the western world, the association of interstitial lung disease with epidermal growth factor receptor has attracted a lot of attention in the recent times. Various researches working with murine models of bleomycin-induced pulmonary fibrosis have found a pro and con role of the receptor in development of the interstitial lung disease. We present the case of a patient diagnosed with stage IV adenocarcinoma of the lung with metastasis to brain. He was found to be positive for the human epidermal growth factor mutation and was hence started on erlotinib. Within a few weeks of starting the medicine the patient was admitted with diarrhea. During the course of this admission he developed acute shortness of breath diagnosed as interstitial pneumonitis. The purpose of this case report is to review the literature associated with erlotinib induced interstitial pneumonitis and make the practicing oncologists aware of this rare yet fatal complication of erlotinib. Here we will also review literature, pertaining to the role of epidermal growth factor receptor in development of interstitial lung disease.

Introduction: Rivaroxaban is a target specific oral anticoagulant approved for treatment of deep venous thromboembolism (DVT), pulmonary embolism (PE) and risk reduction in patients with DVT/PE requiring continued anticoagulation. The XALIA study showed a reduced bleeding risk compared to standard anticoagulation therapy; however, there is paucity of data regarding correlates of bleeding risk amongst patients receiving rivaroxaban in the community setting. We aimed to investigate the clinical factors associated with bleeding events (BE) in patients receiving rivaroxaban for treatment of DVT/PE. Methods: A retrospective study was conducted at John H. Stroger, Jr. Hospital of Cook County. We screened the charts of 837 patients who received rivaroxaban from January 1, 2015 to April 01, 2018. Patients with DVT/PE were included in the study (n=271). Patients with atrial fibrillation and those receiving rivaroxaban for prophylaxis were excluded. Any reported BE was recorded as either major or minor bleeding event. Major BE was defined as events requiring hospitalization, blood transfusions or significant drop in hemoglobin (>2gm/dL). Rest of the BE were classified as minor BE. Socio-demographic and clinical factors were collected. Chi-square test and fisher exact test were used as the tests of trend. Multivariate logistic regression models were used to quantify the independent predictors. Odds ratios (OR) and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were obtained. Results: The study included 271 patients, of which 68.3% were African-American, 14.4% were Caucasian, and 12.9% were Hispanic. Median age was 53 years and 60.9% patients were men. Bleeding events were reported in 11.4% (n=31) patients with 6.3% major bleeding events and 5.2% minor bleeding events. Only concurrent use of aspirin (23.8% vs. 9.2%; OR 3.10, 95% CI 1.34-7.17, P = 0.008) was significantly associated with bleeding events. None of the clinical parameters, like abnormal liver function tests (11.4%), cirrhosis (3.3%), chronic kidney disease stage 3 or worse (7.6%), prior use of warfarin (29.9%) or low molecular weight heparin (18.1%) were associated with bleeding events. In multivariate model adjusted for age, gender and race, concurrent use of aspirin (aOR 3.06, 95% CI 1.23-7.62, P = 0.017) remained independent predictor of bleeding events. Conclusion: In the community practice, aspirin (81mg or 325mg) is prescribed for cardio-protection. A recently concluded trial showed a better cardioprotective effect of combining rivaroxaban and aspirin, without increase in BE in patients with stable cardiovascular disease. However, such data is not evident in patients receiving rivaroxaban for DVT/PE. Our study shows an increased rate of bleeding events in such patients with concurrent use of aspirin. Our study population comprises of two-third African-American patients who are under-represented in the clinical trials. Based on our results we would suggest further investigation in safety of prescribing aspirin with rivaroxaban in patients with DVT/PE in prospective trials. Disclosures No relevant conflicts of interest to declare.

e21104Background: Clinical stage at diagnosis determines prognosis in lung cancer. One third of patients are metastatic at diagnosis with median survival of 1 year. Lately, survival has improved wi...

e17038Background: Upfront docetaxel (UD) in castration-sensitive metastatic prostate cancer (CSPC) has improved failure-free and overall survival in the CHAARTED, GETUG-AFU 15 and STAMPEDE trials, ...

e20039Background: Carfilzomib (Ky) is an irreversible proteasome inhibitor. Phase III trials, ASPIRE and ENDEAVOR reported cardiovascular adverse events (CvAE) associated with Ky. We performed this...

e17020Background: Sarcopenia refers to the functional decline associated with severe deficiency of skeletal muscle mass (lumbar skeletal muscle index (SMI) < 55cm2/m2 for males). The objective of t...

359 Background: Upfront docetaxel (UD) in castration-sensitive metastatic prostate cancer (CSPC) has improved failure-free and overall survival in the CHAARTED, GETUG-AFU 15 and STAMPEDE trials, resulting in a paradigm shift in practice patterns. However, the impact of docetaxel-based chemotherapy regimens in minorities and in real-world practice remains to be described. The objective of this study is to evaluate tolerability and response to UD in an inner-city ethnically diverse CSPC cohort. Methods: We retrospectively reviewed clinical data for CSPC patients at Cook County Hospital. Patients treated with UD and androgen deprivation (UD, n = 49, 2013-17) were compared to those receiving androgen deprivation alone (ADT, n = 42, 2010-17) using descriptive statistics and Cox Proportional Hazards analysis. Results: Median age was 59 and 60 years in UD and ADT, respectively. African Americans, Hispanics and Caucasians formed 69%, 18%, and 10% in UD and 64%, 9.5% and 26% in ADT. Median PSA at diagnosis was: UD 536 [72-1110] ng/ml, ADT 229 [54-999] ng/ml (p = 0.3). Gleason score > 7 was present in 89.8% [UD] and 92.8% [ADT]. UD and ADT had similar frequency of bone (91% vs. 95%, p = 0.5), visceral (12.2% vs. 11.9%, p = 0.9) and retroperitoneal nodal metastases (55% vs. 45.2%, p = 0.3). UD was initiated a median of 8 weeks from diagnosis. 94% in UD received > 3 cycles of chemotherapy. CTCAE grade > 3 events included anemia (6%); neutropenia (6%); infection (4%); diarrhea (4%); peripheral neuropathy (6%), and fatigue (2%). Median PSA nadir was 3.2 [0.5-40.1] vs. 3.45 [0.1-36.4] ng/ml and time to nadir was 20 [13-27] vs. 41 [19-69] weeks in UD vs. ADT. Biochemical progression was observed in 34.7% [UD] vs. 40.5% [ADT]. Median time to castration-resistance was UD: 39 [31-67] vs. ADT: 65 [34-76] weeks [HR: 0.9; 95% CI 0.4-1.8; p = 0.7]. There were 12 deaths [UD: 4; ADT: 8] during a median follow-up of 46 [23-86, UD] and 111 [68-157, ADT] weeks. Conclusions: In a diverse underserved population with CSPC, UD was well tolerated but was not associated with improvement in time to castration compared to ADT. These results warrant validation and underscore the importance of ensuring accrual of minorities in clinical trials.

We have previously shown that dichlorodiamine platinum (DDP), or cisplatin, a cancer chemotherapeutic agent, is effective in the treatment of malignancy-associated hypercalcemia. In the present studies, we evaluated its effects on bovine parathyroid hormone (PTH)- or tumor-induced bone resorption in vitro in the neonatal mouse calvarial bone resorption assay. PTH alone or tumor extract (TE) of a human squamous cell lung cancer alone caused a significant increase in the bone resorption and in the number of osteoclasts in the calvaria. The addition of 3 and 10 micrograms/ml DDP inhibited the PTH- or TE-induced bone resorption. Lower doses of 1 and 2 micrograms/ml DDP, although not effective in inhibiting the PTH-induced bone resorption, were effective in lowering the TE-induced bone resorption. The number of osteoclasts was also reduced by DDP treatment. We therefore conclude that DDP is effective in the treatment of malignancy-associated hypercalcemia by virtue of its inhibitory effects on osteoclast numbers and on bone resorption.

Transforming growth factors (TGFs) have been implicated in the pathogenesis of the hypercalcemia in malignancy (HM). In order to evaluate the role of these growth factors (epidermal growth factor (EGF) and TGF-alpha acting via the EGF receptor) in the development of HM, we studied the effect of 2 doses of EGF (0.1 and 0.3 microgram/g/day) given for 7 days as a continuous infusion on serum and urine calcium in athymic mice. These infusions had no effect on serum and urine Ca values in this study. In order to assess the biological activity of the infused EGF, other known effects on gastric and pancreatic weights were evaluated. EGF-infused animals had significantly greater gastric and pancreatic weights than controls. Thus, EGF infusion into mice in doses which elicited known biological effects failed to have an effect on serum and urine Ca. An infusion of bovine parathyroid hormone 1-34 at the dose of 0.1 microgram/g/day resulted in significant hypercalcemia.

e20635 Background:Metastatic lung cancer with systemic chemotherapy has a median progression-free survival (PFS) of 5-6 months and median overall survival time (OS) of around 12 months. In Epidermal Growth Factor Receptor gene (EGFR) mutated metastatic lung cancer the use of EGFR Tyrosine Kinase Inhibitors (EGFR-TKIs) has increased the median PFS to12 months and the median OS to 30 months. The objective of this study is to evaluate the response to TKIs in EGFR mutated metastatic lung cancer in racially diverse inner city population with high smoking rates. Methods:Consecutive patients diagnosed with EGFR mutant metastatic lung adenocarcinoma and treated with TKIs in John H. Stroger Jr. Hospital of Cook County in Chicago, IL between January 2009 to June 2016 were retrospectively evaluated. Demographic data was collected and PFS and OS were analyzed. Results:35 patients with EGFR mutated metastatic lung cancer received EGFR-TKI during the study period. There was a female preponderance (63%). Hispanics formed the most common racial group (37%), followed by Asians (26%), African Americans (AA) (20%) and Caucasians (17%). Mean age of diagnosis of metastatic disease was 56.5± 11.5 years. 20% of the patients were ever smokers. Stage 4 disease at presentation was seen in 88.6 %. Sites of metastatic disease included lungs/pleura (60%), bone (60%), brain (22.9%) and liver (14.3%). 82.9% had TKI as first line treatment. Median PFS and OS were 9.89 (95% CI: 7.8-11.9) months and 19.3 (95% CI: 1.9-36.8) months respectively. The median PFS and OS were 12.88 and 17 months for Asians, 10.8 and 24.4 months for Caucasians and 9.2 and 33 months for Hispanics respectively. Among AA, PFS at 19 months and OS at 35 months was 0.58%, not reaching the median. Patients who continued to smoke had a median OS of 8.5 months vs 19.3 months in nonsmokers/ex-smokers. Conclusions: In an underserved population, patients treated with EGFR mutated metastatic lung adenocarcinoma with EGFR-TKI have similar survival compared previously known data. Race of the patient does not appear to alter response to EGFR-TKI therapy. Active smokers had a lower OS. Studies in minority populations with larger samples are required to further validate the above findings.

Summary Background 9-Aminocamptothecin (9-AC) is a synthetic analogue of camptothecin. Phase I studies, identified the maximum tolerated dose as 1416 μg/m2/day × 3 as continuous intravenous infusion (CVI) with dose-limiting neutropenia. Patients and methods Eligible patients had stage IIIB or IV non-small-cell lung cancer (NSCLC) with measurable disease. Patients were initially treated at 1416 μg/m2/d × 3 by CVI followed by granulocyte-colony stimulating factor (G-CSF) support. This dose was decreased to 1100 μg/m2/d after the first 13 patients. Cycles were repeated every 14 days until tumor progression. Results Fifty-eight patients were treated, thirteen at 1416 μg/m2/d and 45 at 1100 μg/m2/d. Fifty percent had adenocarcinoma and 17% squamous cell carcinoma. Seventy-one percent had stage IV disease. Five patients had a partial response (response duration 9–28 weeks) for an overall response rate of 8.6%, (95% confidence intervals (CI): 2.9%–19%). Median time to progression was 2.3 months and the median survival for the entire study population 5.4 months with a one-year survival rate of 30%. The one-year survival rate for 27 patients who received second line chemotherapy was 56.7%. Toxicities at 1416 μg/m2/d included grade 4 neutropenia and thrombocytopenia in six and five of 13 patients, respectively; at 1100 μg/m2/d these toxicities were observed in 12 and three of 45 patients, respectively. Conclusion 9-AC has modest single-agent activity in previously untreated NSCLC. Its further evaluation at the dose and schedule employed in this study does not seem indicated. Exploration of more prolonged administration schedules may be warranted.

Purpose The purpose of this study is to determine whether primary treatment with both radiotherapy and chemotherapy is superior to radiotherapy alone in patients with squamous cell carcinoma of the esophagus. Patients and methods From January 1980 to December 1988, 77 patients from two Veterans Affairs hospitals with clinically staged nonmetastatic squamous cell carcinoma of the esophagus received either radiotherapy alone (RT group) or concomitant radiotherapy and chemotherapy (RT + CT group) with curative intent. Each group originated at a different hospital, but all patients were irradiated in the same radiotherapy department. Chemotherapy consisted of cisplatin and 5-fluorouracil. Forty-two patients received RT alone, and 35 received RT + CT. Locoregional control, disease-free survival, and overall survival rates were compared. Results Locoregional control, disease-free survival, and overall survival rates were significantly higher in the RT + CT group when compared to RT group, 26% vs 5%, 20%, vs 2%, and 29% vs 7%, respectively, at 2 years (P = .01, 0.02 and 0.02, respectively). The median survival was 14 months for the RT + CT group and 7.5 months for the RT group. There was no difference in the incidence of distant metastases except for bone metastases. No one in the RT + CT group developed bone metastases compared to nine patients in the RT group (P = .01). Conclusion This retrospective analysis shows improved locoregional control, disease-free survival, and survival when chemotherapy consisting of cisplatin and 5-FU is given in addition to radiation for patients with squamous cell carcinoma of the esophagus. Bony metastases were absent in those who received chemotherapy.

Amonafide (nafidimide), a synthetic organic compound with an inhibitory effect on cellular replication, was used in a phase II study conducted by the Illinois Cancer Center in order to assess its efficacy and toxicity in advanced or recurrent squamous cell cancer of the head and neck. Eligible patients had received no more than one prior adjuvant or neoadjuvant chemotherapy, had normal bone marrow, renal and hepatic function, ECOG performance status of 0–2, and bidimensionally measurable disease. Eligible patients were administered amonafide at a starting dose of 300 mg/m2 for five consecutive days every 3 weeks with dose escalation or de-escalation according to established hematologic criteria in the absence of disease progression. Nineteen of 22 entered patients were evaluable for response and all patients were evaluable for toxicity. Eleven of 19 patients achieved stable disease. Median time to progression after start of treatment was 57 days, for the 18 patients for whom the date of progression is known. There were no partial or complete responses. Hematologic toxicity was dose limiting with grade 3–4 neutropenia in 50 percent of patients and 4 deaths associated with neutropenic sepsis. Non-hematologic toxicity was mild to moderate with nausea and vomiting predominating. In this study, amonafide was a myelotoxic, inactive treatment in advanced/ recurrent head and neck cancer. Further use in head and neck cancer appears unwarranted.

e18195Background: John Stroger Hospital is one of the largest public hospitals in the country, providing chemotherapy to 60-70 patients a day. Over 2014-2015, we designed, built and now use 285 ele...

Background In advanced non–small-cell lung cancer (NSCLC), reducing symptoms can be a meaningful treatment outcome. This study characterizes the pulmonary symptoms of patients receiving second- and third-line systemic therapies for NSCLC and assesses the content validity of the 4-item Pulmonary Symptom Index (PSI) of the Functional Assessment of Cancer Therapy—Lung (FACT-L). Methods Twenty patients with advanced NSCLC undergoing second- and third-line treatment (“qualitative sample”) completed semistructured interviews regarding their NSCLC symptoms and the importance of pulmonary symptoms. Results were mapped to the PSI. In addition, existing PSI data from 912 patients with cancer (“validation sample”) was analyzed to evaluate the scalability of the 4 PSI items. Results In the qualitative sample, mean age was 62 years (range 30-79 years); 80% had nonsquamous histologic type, and 25% had comorbid chronic obstructive pulmonary disease (COPD). A core set of pulmonary symptoms emerged in the data—shortness of breath, cough, and chest tightness. These mapped to 3 PSI items. A quarter of the patients reported an absence of pulmonary symptoms, which supports the inclusion of the final PSI item, “breathing is easy.” In the validation sample, for the shortness of breath/breathing ease item pair, weighted kappa representing chance-adjusted agreement ranged from 0.39 to 0.54 and percent agreement from 44% to 49% (both considered moderate), supporting a distinct contribution of each item. Conclusion The PSI captures the most important and relevant symptoms reported by patients with NSCLC receiving second- and third-line treatment. Our results suggest that the PSI may provide a clinically useful method to measure patient benefit from lung cancer therapies.

Between June 1988 and January 1980, 67 patients with pathologic stage III non-small cell lung cancer were randomized to receive either preoperative mitomycin, vinblastine, and cisplatin (MVP) chemotherapy (cisplatin 120 mg/m 2 , and mitomycin, 8 mg/m 2 day 1+29, and vinblastine, 4.5 mg/m 2 on day 1, 15, 22, and 29 and 2.0 mg/m 2 day 8), or preoperative radiotherapy (44 Gy in 22 fractions to the primary tumor and mediastinum). The purpose of this study was to identify a treatment approach that showed sufficient effectiveness and acceptable toxicity to warrant testing by prospective randomized trial against "standard" nonsurgical treatment. All patients had surgical staging of the mediastinum and had either unresectable N2 disease or T4 disease with proximal extension of disease along the pulmonary artery. Response to preoperative therapy was evaluated 8 weeks after beginning treatment and patients with complete or partial radiographic response were to undergo surgical exploration and resection if possible. Fifty-seven patients were eligible and evaluable for response. Of the 67 total patients, 3 were unavailable for follow-up, 4 were ineligible, 1 was canceled, and 2 refused all treatment after having been randomized. Of the eligible and evaluable patients, 49 had stage IIIA and 8 had stage IIIB disease. Randomization was to MVP in 26 cases and to radiotherapy (XRT) in 31. Radiographic response to treatment was virtually identical for the two approaches, with 29 of the 57 evaluable patients achieving objective responses. In patients achieving radiographic response, 24 underwent surgical exploration and 20 underwent resection, of which 18 were complete. The mediastinum was free of tumor in seven patients but only two pathologic complete responses were seen (one each to XRT and MVP). In addition, ten nonresponders underwent surgery; seven underwent resection. Median survival for the entire group is 12 months, with a 27% actuarial survival at 4 years. Two patients died of treatment toxicity during preoperative therapy. Overall toxicity included 2 preoperative toxic deaths and 6 postoperative deaths in 34 patients who underwent surgical exploration (3 each with XRT and MVP) due to adult respiratory distress syndrome (3), myocardial infarction (1), pulmonary edema (1), and esophageal fistula (1), for an overall death rate 8 of 57 (14%) and a perioperative death rate in surgically explored patients of 6/34 (18%). These preoperative regimens, in the population studied herein, were of modest efficacy and substantial toxicity. While these data do not exclude possible gain in long-term survival for these preoperative treatments compared with the best nonsurgical therapy, until such benefits are documented in prospective trials, their use should be considered investigational.

This study was conducted to determine the effect of adjuvant chemotherapy on locally advanced resected non-small cell lung cancer. Anatomic eligibility requirements were either positive resection margins or tumor involvement of the highest sampled mediastinal lymph node. One hundred seventy-two patients were randomized to receive either postoperative thoracic irradiation alone or together with six cycles of CAP chemotherapy (cyclophosphamide, doxorubicin, and cisplatin). The chemotherapy arm showed significantly longer recurrence-free survival (p=0.004). This benefit accrued to patients with both nonsquamous (p=0.01) and squamous (p=0.08) cell carcinoma. At 1 year following randomization, there was a 14% difference in survival favoring the chemotherapy arm. Chemotherapy significantly reduced distant metastases. Median survival was 20 months for the chemotherapy arm and 13 months for the radiotherapy alone arm. The 2-year survival rate for the entire study population was 35%. Toxic reactions were primarily predictable hematologic, GI, and alopecia toxicity expected from CAP. Esophagitis was not a significant problem.

Fourteen patients with squamous cell carcinoma of the head and neck received 9-AC/DMA infusions of 850 mg/M2/day over 72 hours. Eligibility criteria included good performance status, advanced disease incurable by conventional means, no prior treatment of metastatic disease, and measurable lesions for objective response assessment. The infusions were repeated at 21 day intervals until progression or prohibitive toxicity occurred. A median of 3 cycles (range 1-7) was given. No objective responses were observed. Median survival of the group was 6 months. Toxicity was hematologic which was modest and promptly reversible. 9-AC/DMA is inactive against this tumor type at the dose and schedule employed in this study.

In a prospective, randomized, double-blind, multicenter study, 202 patients with cancer from 19 medical centers were treated for hypercalcemia of malignancy with daily intravenous infusions of etidronate disodium (136 patients) or saline alone (66 patients) for 3 consecutive days. Patients also received up to 3.25 L of saline daily during the treatment period. Of 157 patients for whom data could be evaluated for efficacy, 63% (72/114) of etidronate-treated and 33% (14/43) of saline-treated patients had a normalization of total serum calcium levels. When serum calcium levels were adjusted for albumin (147 assessable patients), 24% of the etidronate- and 7% of the saline-treated patients responded to treatment. No serious side effects or treatment-related deaths occurred. When accompanied by adequate hydration and diuresis, intravenous etidronate was safe and more effective than hydration and diuresis alone in controlling hypercalcemia of malignancy.

Patient-reported outcomes (PROs), such as symptom scales or more broad-based health-related quality-of-life measures, play an important role in oncology clinical trials. They frequently are used to help evaluate cancer treatments, as well as for supportive and palliative oncology care. To be most beneficial, these PROs must be relevant to patients and clinicians, valid, and easily understood and interpreted. The Patient-Reported Outcomes Measurement Information System (PROMIS) Network, part of the National Institutes of Health Roadmap Initiative, aims to improve appreciably how PROs are selected and assessed in clinical research, including clinical trials. PROMIS is establishing a publicly available resource of standardized, accurate, and efficient PRO measures of major self-reported health domains (eg, pain, fatigue, emotional distress, physical function, social function) that are relevant across chronic illnesses including cancer. PROMIS is also developing measures of self-reported health domains specifically targeted to cancer, such as sleep/wake function, sexual function, cognitive function, and the psychosocial impacts of the illness experience (ie, stress response and coping; shifts in self-concept, social interactions, and spirituality). We outline the qualitative and quantitative methods by which PROMIS measures are being developed and adapted for use in clinical oncology research. At the core of this activity is the formation and application of item banks using item response theory modeling. We also present our work in the fatigue domain, including a short-form measure, as a sample of PROMIS methodology and work to date. Plans for future validation and application of PROMIS measures are discussed.

6593 Background: RT-related early adverse skin reactions (EASR) are common in BC patients. EASR occur during/within 2 months post-RT. Predictive biomarkers for EASR are under active investigation. ...

Importance Observational studies suggest a role for dietary nutrients such as vitamin E and selenium in cataract prevention. However, the results of randomized clinical trials of vitamin E supplements and cataract have been disappointing and are not yet available for selenium. Objective To test whether long-term supplementation with selenium and vitamin E affects the incidence of cataract in a large cohort of men. Design, Setting, and Participants The Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints Study was an ancillary study of the Southwest Oncology Group–coordinated SELECT, a randomized placebo-controlled 4-arm trial of selenium and vitamin E conducted among 35 533 men, 50 years and older for African American participants and 55 years and older for all other men, at 427 participating sites in the United States, Canada, and Puerto Rico. A total of 11 267 SELECT participants from 128 SELECT sites participated in the SELECT Eye Endpoints ancillary study. Interventions Individual supplements of selenium (200 μg per day from L-selenomethionine) and vitamin E (400 IU per day of all rac-α-tocopheryl acetate). Main Outcomes and Measures Incident cataract was defined as a lens opacity, age related in origin, and responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-reports confirmed by medical record review. Cataract extraction was defined as the surgical removal of an incident cataract. Results During a mean (SD) of 5.6 (1.2) years of treatment and follow-up, 389 cases of cataract were documented. There were 185 cataracts in the selenium group and 204 in the no selenium group (hazard ratio, 0.91; 95 % CI, 0.75-1.11; P = .37). For vitamin E, there were 197 cases in the treated group and 192 in the placebo group (hazard ratio, 1.02; 95 % CI, 0.84-1.25; P = .81). Similar results were observed for cataract extraction. Conclusions and Relevance These data from a large cohort of apparently healthy men indicate that long-term daily supplementation with selenium and/or vitamin E is unlikely to have a large beneficial effect on age-related cataract. Trial Registration ClinicalTrials.gov Identifier:NCT00784225

Bisphosphonates reduce the incidence of skeletal-related events (fractures, pain, hypercalcemia) in patients (pts) with bone metastases from breast cancer. By inhibiting osteoclast function and subsequent bone turnover they may inhibit the growth of bone (and other) metastases. Their role in preventing or delaying the development of bone (or other) metastases in pts with early breast cancer is uncertain. Three previous trials of oral clodronate have given mixed results. The largest trial (placebo-controlled) and a smaller open-label trial suggested that oral clodronate benefitted pts with improved bone metastases-free survival (BMFS) and overall survival (OS), but a third open-label study showed no benefit with an apparent detrimental effect on survival. Studies of IV zoledronate in open-label trials in early breast cancer have also shown mixed results: the AZURE trial in pts with node positive breast cancer showed no benefit in disease-free survival (DFS) or OS with a possible effect in pts aged over 60. The ABCSG-12 trial in GnRH (plus tamoxifen or anastrozole) treated women with early breast cancer showed a small DFS benefit for those receiving IV zoledronate but no BMFS or OS benefit. Methods: B-34 is a prospective, randomized, double-blind, phase III clinical trial in pts with stage 1, 2 or 3 breast cancer assessing oral clodronate 1600mg daily for 3 years compared to placebo given alone or in addition to adjuvant chemo- or hormone therapy. Stratification is by age ( Results: 3323 patients were accrued — 1662 in Group A and 1661 in Group B. As of March 31, 2011, 54 pts were declared ineligible: 23 in Group A and 31 in Group B. The average time on study is 101.3 months. Patient characteristics were evenly distributed throughout both groups. Approximately 75% of pts in each group had negative axillary lymph nodes and some 78% in each group were ER and/or PR positive. About 64% of pts were age 50 or over. Oral clodronate was generally tolerable, toxicities observed being mainly due to the concomitant systemic chemotherapy. One pt in Group A had a 1 mm area of osteonecrosis on the palatal taurus. Compliance, as expected with trials of oral medications, has been a problem. 1910 pts completed 3 years of therapy. Event rates were slower than anticipated. This final analysis assesses a total of 598 events in the two arms. Conclusions: This trial is the largest placebo-controlled study of an oral bisphosphonate in patients with early breast cancer and will provide further information on the role of bisphosphonates in breast cancer management. Supported for NSABP by NCI U10CA12027, −37377, 69651, 69974; and Bayer Schering Pharma Oy; for ECOG by U10CA021115; for NCCTG by U10CA25224; for SWOG by U10CA38926. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S2-3.

Background: Hepatocellular cancer (HCC) is the fifth most frequently diagnosed cancer in the world and the second leading cause of cancer-related death across the globe. There are few small and old studies that tried to correlate levels of alpha-fetoprotein (AFP) with patient outcomes. Currently with more screening there is early diagnosis of HCC and the therapeutic options for non-surgical candidates have also improved in the past decade. We undertook this study to see if the level of elevation of AFP is related to patient prognosis in the current era.

e20544 Background: Poor sleep is common, and is linked to impaired cognitive, psychological, and physical functioning and a lower quality of life. The purpose of this study is to measure quality of sleep in cancer patients and determine the relationship between quality of sleep and performance status. Methods: Patients with cancer (n=139) were recruited at the public hospital between November 2011 and January 2012 and asked to complete the Pittsburgh Sleep Quality Index (PSQI) and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) questionnaires. Twenty patients repeated the questionnaires after 3 months. For the purpose of this study PSQI global score >5 was considered insomnia. PS score 0-1 was considered good, and PS 2-4 was considered poor. Results: The mean age of participants was 55±11 years, 56% were women, 78% were ethnic minority, 77% had advanced cancer, and 71% were undergoing cancer treatment. Among all patients, 73% reported good PS. Median PSQI score was 7 (IQR 4; 11) and 62% had insomnia. Sleep medication was used by 25%. Patients with poor PS had worse PSQI score (Mann-Whitney test, p< 0.0001), and 7.34 (95%CI 2.11-25.49) higher odds of insomnia (p=0.0002) compared to patients with good PS.(Table1) No significant correlation was found between insomnia and gender, ethnicity, primary tumor type, tumor stage, or treatment status. Conclusions: The incidence of insomnia among cancer patients is high. There is a higher incidence of sleep disturbance and worse sleep quality among patients with poorer performance status. [Table: see text]

9085 Background: Capecitabine is an oral fluoropyrimidine that is used to treat various malignancies. Hand and Foot Syndrome (HFS) is a dose limiting toxicity of capecitabine and can limit the use of this agent in some patients. Some investigators have observed that pyridoxine (vitamin B6) can ameliorate HFS caused by capecitabine. We designed a prospective trial to determine if pyridoxine can prevent HFS in patients receiving capecitabine. Methods: In our double-blind, placebo controlled trial, we randomly assigned eligible patients treated with capecitabine to receive either daily pyridoxine 100 mg or placebo along with their capecitabine-containing chemotherapy regimen. Patients were observed during the first four cycles of capecitabine treatment. The primary end point was the incidence and grade of HFS that occurred in both arms. Results: Between 2008 and 2011, 77 patients were randomly assigned to receive either pyridoxine (n=38) or placebo (n=39). Both arms were matched in baseline characteristics. The median age was 53.5 years. The ethnic composition of the study population was African American 53%, Caucasian 22%, Hispanic 18%, and Asian 7%. The daily doses of capecitabine were: 2000 mg/m2 (69 pts), 1650 mg/m2 (5 pts), 1400 mg/m2 (2 pts) and 1000 mg/m2 (1 pt). Dosages of capecitabine were equally matched between the two arms of the study. HFS occurred after a median of 2 chemotherapy cycles in both groups. HFS developed in 10/38 (26%) patients in the pyridoxine group and in 8/39 (20%) patients in the placebo group (p=0.547). Therefore, the risk of HFS was 6 percentage points higher in pyridoxine group (95% CI for difference: -13 percentage points to +25 percentage points). Given our study results, we can be confident of excluding a true benefit from pyridoxine larger than 13 percentage points. No difference in HFS grades was observed. Conclusions: Prophylactic pyridoxine (vitamin B6), given concomitantly with capecitabine-containing chemotherapy, was not effective for the prevention of HFS. [Table: see text]

African Americans are more likely to develop lung cancer and die from it than any other ethnic group. Complex biological, environmental, political and cultural factors contribute to this disparity. The purpose of the current project is to examine the relationship between epigenetic factors, gender, ethnicity and outcome in a retrospective study of patients with surgically-treated early stage lung cancer. Fixed primary tumor tissues from a private (RMC) and a public (JHS-CCH) institution were analyzed in this study. The RMC group consisted of 132 patients with stage Ib, IIa and IIb NSCLC, 22% African-American (AA) and 52% female. The JHS-CCH group consisted of 88 patients, 62% AA and 43% female. Five year survival was achieved by 85% of women vs 67% of men in the RMC group (Chi square p=0.022). 68% of Caucasians vs 53% AA survived five years in the RMC group (p=0.186). To investigate the role of epigenetic influences on survival, promoter methylation of Ras association domain family protein 1, RASSF1A, was investigated. Associations between inactivation of the RASSF1A tumor suppressor and poor outcome in lung and other cancers have been reported in several studies. Promoter methylation was quantified using pyrosequencing. Percent methylation of RASSF1 at cytosine position –36 (A of ATG=+1) was more frequent in AA (41% of cases) than in Caucasians (20% of cases) in the RMC group (p=0.023) compared to 69% of cases in the JHS-CCH group. Methylation levels of RASSF1 at all CpG sites tested were higher in the JHS-CCH group than in the RMC group. Kaplan-Meier analysis was performed on dichotomized hypermethylation status compared to five-year survival (5YS). Promoter hypermethylation of RASSF1 was significantly associated with shortened 5YS in AA (p=0.005), compared to Caucasians (p=0.197) in the RMC group. Although 5YS was marginally shortened with hypermethylation of RASSF1 in men in the RMC group (p=0.123), no significant effects were seen with regard to gender. These results suggest that biomarkers can have differential effects, based on genetic background and support analysis of epigenetic biomarkers to address disparities and develop more personalized treatment strategies for individual patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3586. doi:1538-7445.AM2012-3586