tbuckley/cabot-search huggingface dataset:
Impact of prostate cancer diagnosis and type of treatment on the health-related quality of life and urological dysfunction at 3 years: A case-control study.
Authors: Florence Menegaux, Xavier Rebillard, Brigitte Tretarre, Sophie Bouvet, Christel Castelli, Frederic Fiteni, MD PhD, Nadine Houede
Journal: Journal of Clinical Oncology (2018)

e17084 Background: Former studies showed a time-dependent worsening of sexual or urinary long term side effects following surgery or radiotherapy that affected prostate cancer (PCa) patients’ health-related quality of life (HRQoL) though it was not possible to discriminate between age- and treatment-related symptoms. We sought to compare HRQoL and urological dysfunction at 3 years between PCa patients and general population based on the data from the EPICAP population-based case-control study. Methods: Eligible cases were men < 75 years old, diagnosed with PCa between 2012 and 2014. Controls were recruited in the general population and paired on age. Questionnaires were given to the patients at 3 years after intervention. Primary objective was to compare HRQoL using the EORTC QLQ-C30 questionnaire at 3 years between patients and the general population. Secondary objective was to perform the same comparison for the impact of diagnosis or/and treatments on urinary (IPSS, ICS) or sexual dysfunctions (IEEF-5), anxiety (HADS), and occupational integration. Results: 376 eligible patients had sent back their questionnaires and 188 controls were paired on age (ratio 2:1). Treatments were: RP (radical prostatectomy) (187), RT (radiation therapy) or HIFU (High-intensity Focused Ultrasound) (54), combination of treatment (CT) (90) and watchful waiting (WW) (39) at the time of the study. There was no difference in global health status dimension between patients and controls (p = 0.19). Patients had worse social functioning than controls (24.3% vs 16.3%, p = 0.0209) and cognitive function score was worse in CT versus WW patients (p = 0.039). Significant differences in erectile dysfunction (IIEF6) were observed depending on treatment (81% for RP vs 65% for RT vs 72% for CT vs 33% for WW, p < 0.0001). Conclusions: Despite similar global health status dimension score at 3 years after diagnosis between patients and controls, analyzes of the EPICAP study showed differences in PCa sequelae and emphasize the balance between benefit and risk of PSA testing. This is the first study evaluating the different types of sequelae as a function of treatments.
Dynamic testing of positive and negative biomarkers on peripheral blood cells at early stages of immunotherapy predicts response in advanced cancer patients.
Authors: Wushuang Du, Yi Hu
Journal: Journal of Clinical Oncology (2018)

e15131 Background: Immunotherapy against malignant tumors shows outstanding clinical efficacy, especially agents targeting the programmed death 1 (PD-1) pathway. In this study, we intended to dynamically determine the relationships between clinical benefit and changes in immune biomarkers on peripheral blood monocular cells (PBMCs) and try to set up a model to predict the response at early stage in the “real world”. Methods: All patients recruited were treated in the Cancer Center of the Chinese People’s Liberation Army from December 2016 to July 2017.A total of 25 patients treated with nivolumab or pembrolizumab, either with or without chemotherapy, were enrolled in our study. We investigated nine checkpoint molecules including PD-1, CTLA-4, TIM-3, LAG-3, BTLA, CD160, Ki-67, OX40 and GITR on CD4+, CD8+ and NK cells by flow cytometry in patients before and after receiving each treatment with anti-PD-1 agents. Results: We found that the responder group showed higher expressions of PD-1 on CD4+ and NK cells than the non-responder group after initiation of immunotherapy, and lower expression of CTLA-4, GITR and OX40 after a second round of immunotherapy. A simple model of combination of biomarkers was generated to predict the immunotherapeutic effect, revealing that elevation of key biomarkers after the first cycle of immunotherapy, followed by a decrease in expression after the second cycle, was associated with better benefit from immunotherapy at early stage. Conclusions: Our work indicates that by testing patients’ PBMCs at an early stage of treatment, the immunotherapeutic effect can be predicted, thus improving cost efficiency and patient outcomes.
Nutrition assessment among men undergoing genetic counseling for inherited prostate cancer: A teachable moment.
Authors: Veda N. Giri, Michael Bruneau, Elias Obeid, Christa Smaltz, Brandy-Joe Milliron
Journal: Journal of Clinical Oncology (2018)

1519 Background: Genetic counseling (GC) for men with or at-risk for prostate cancer (PCA) is growing with advancements in genetic testing (GT). GC provides a unique opportunity to promote a healthy lifestyle and is understudied in men. We conducted a targeted dietary analysis of men with or at-risk for PCA who have undergone GC and GT in the Genetic Evaluation of Men (GEM) study at two academic centers. Methods: GEM participants completed a structured lifestyle questionnaire (QA) which included dietary behaviors. QA included frequency of consuming six different types of foods (rich in vitamins C, A and D, cruciferous vegetables, rich in lycopene, smoked and/or salted meats) and daily servings for specific food groups (red meat, seafood, chicken, legumes/other protein sources, vegetables, fruit, grains, milk products, foods high in saturated fat) and alcohol. Diet intake was compared to USDA’s dietary recommendations for cancer survivorship. Distributions of dietary consumption were assessed by PCA status, PCA aggressiveness (Gleason > 7, T3, or metastatic disease), family history (FH), and body mass index (BMI) with Chi-Square contingency analyses and adjusted residuals (adj resid). Alpha levels were set a priori at p < .05. Results: Self-reported dietary data among men with PCA (n = 239) and at-risk for PCA (n = 81) who underwent GC was included. Overall, 84% were overweight/obese per CDC guidelines. Consumption of Vitamin C 1-2 times per week was significantly lower among men with aggressive PCA (adj resid = -1.9) vs. less aggressive PCA (adj resid = 1.9). Men with aggressive PCA also reported eating more red meat vs less aggressive PCA (p = 0.011). A higher percentage of men with aggressive PCA and higher weight did not meet the recommended guideline for vegetables (p = 0.047) and red meat (p = 0.015) than expected per contingency analyses. Conclusions: In this sample, specific dietary patterns were associated with aggressive PCA. A high proportion of men receiving GC for inherited PCA were overweight and/or obese, affording a teachable moment for lifestyle intervention. Key focus areas to develop diet intervention include consumption of less red meat and more vegetables among men at-risk or in survivorship.
The population-based impact of adjuvant chemotherapy (CTx) on outcomes in AJCC6 stage IB non-small cell lung cancer (NSCLC).
Authors: Rahul Krishan Arora, Amanda Williams Gibson, D. Gwyn Bebb, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2018)

8523 Background: Adjuvant CTx is the standard of care in stage II and IIIA NSCLC, but its value in AJCC6 stage IB NSCLC (T2N0M0) is unclear. Guidelines suggest consideration of adjuvant CTx for stage IB patients at high recurrence risk, but CTx use is variable. Prior population-based studies lacked NSCLC-specific survival (CSS) and key covariates such as health insurance status. Using a Canadian cohort with universal health care coverage and CSS data, we aimed to identify predictors of use and assess the real-world benefit of adjuvant CTx in stage IB NSCLC. Methods: We examined all patients who underwent surgery for T2N0M0 NSCLC in a large Canadian province between 2004 and 2015 and categorized cases based on receipt of adjuvant CTx within 6 months of curative resection. We identified predictors of CTx receipt with logistic regression. We also identified correlates of overall survival (OS) and CSS using Kaplan-Meier methods and Cox regression. Results: 967 patients met eligibility criteria. Median age was 68 (IQR 61-74) years at diagnosis, 455 (47%) were men, and 164 (17%) received adjuvant CTx. Sex, topology, and laterality were similar in patients treated with or without CTx. Lower age at diagnosis, lower Charlson Comorbidity Index, large cell histology, and tumor size ≥ 4 cm were associated with higher likelihood of CTx receipt (all p < 0.05). In the entire cohort and in the subset with ≥ 4 cm tumors, CTx improved OS but not DSS on univariate analysis. In both groups, CTx did not correlate with OS or DSS on multivariate analysis (Table). Conclusions: Adjuvant CTx does not improve survival in this real-world cohort of T2N0M0 NSCLC patients, even for patients with ≥ 4cm tumors, suggesting that it has a limited role in real-world practice. Univariate and multivariate survival analysis for stage IB NSCLC patients based on receipt of CTx. All patients ≥ 4 cm tumors CTx No CTx P CTx No CTx p mOS (months) [95% CI] 104 [67-114] 78 [69-86] 0.058 111 [85-137] 71 [55-87] 0.030 mCSS (months) [95% CI] 135 [NR] NR 0.491 135 [NR] NR 0.827 Adjusted HR for OS [95% CI] 0.93 [0.69-1.24] 0.598 0.73 [0.45-1.16] 0.177 Adjusted HR for CSS [95% CI] 1.20 [0.84-1.70] 0.316 0.92 [0.53-1.58] 0.754 m = median; HR = hazard ratio; NR = not reached.
Phase II study with docetaxel (D), cisplatin (C) and continuous capecitabine (X) schedule (DCX) in advanced gastric cancer (AGC): ML21085. Final results.
Authors: Carles Pericay, Ferran Losa, Jordi Alfaro, Luis Cirera, Aleydis Pisa, Antonieta Salud, Esther Falco, Esther Casado, Miquel Nogue, Emma Dotor, Olbia Serra, Julen Fernandez, Eugeni Saigí
Journal: Journal of Clinical Oncology (2016)

e15520 Background: Activity in first line in AGC with D, C and Fluorouracil (V325 study) has been described. Two studies evaluated schedules with X (REAL-2 and ML 17032). But there is no much information about continuous treatment with X in this setting. We performed a prospective study in order to obtain data about the efficacy and tolerability with the schedule DCX in patients (pts) with AGC. Primary endpoint: Overall response rate (ORR). Other secondary endpoints: progression free survival (PFS), overall survival (OS), toxicity. Methods: Patients were enrolled if they had the main subsequent criteria: histologically confirmed diagnosis of AGC (local advanced or metastatic disease); normal renal and hepatic function; no myocardial infarction or angina pectoris; no uncontrolled severe diseases or active infections. Treatment schedule: D at fixed dose of 75 mg/m2 on day 1, C at fixed dose of 60 mg/m2 on day 1, X at fixed dose of 1,300 mg/m2 in two daily administration from day 1 to day 21, every 3 weeks until 6 cycles (cy). Primary profilaxis was used with colony stimulating factors and ciprofloxacin. Informed consent was obtained for all subjects. EUDRACT: 2007-000725-22. Results: From July 2008 to July 2010,44 pts were enrolled. Median age: 58 years (range 30-78). Total administered cycles: 194 (73.5% of total). Median number of administered cycles 4.4 (range 1-6). Cycles received: 1st:44pts, 2nd:41pts, 3rd:35pts, 4th:28pts, 5th:25pts, 6th:21pts. Dose reduction: 7pts, 18cy. Administration delivery: 11cy. Total dose: D: 88.49%, C: 71.51%, X: 74.56%. Efficacy: 40pts died, 3pt alive, 1pt lost-in-follow-up. PFS: 6.82 months (m) (CI95%: 5.09-8.54). OS: 11.86 m (CI95%: 6.47-17.26). ORR: partial response 48.6%, stable disease 29.7%, progression 21.7%. Toxicity G3-4: asthenia 20.5%, mucositis 11.4%, diarrhea 9.1%, neutropenia 7.7%, vomiting 6.8%, hand-foot syndrome 6.8%, nausea 4.5%, febrile neutropenia 3.0%, anorexia 2.3%. Conclusions: The DCX schedule is well tolerated and has a survival close to 12 months. The administration of DCX can be considered in first-line treatment of advanced or metastatic gastric adenocarcinoma and esophagogastric junction. Clinical trial information: 2007-000725-22.
Use of abiraterone and enzalutamide beyond PSA progression in metastatic prostate cancer.
Authors: Daniel Jacob Becker, Arjun Iyengar, Anika Zaman, Jason Ng, Kevin Douglas Becker, Danil V. Makarov
Journal: Journal of Clinical Oncology (2018)

e18921 Background: Abiraterone (abi) and enzalutamide (enza) are costly drugs which extend the lives of prostate cancer patients, but endpoints for clinical progression are unclear. We studied treatment patterns/outcomes with abi/enza throughout PSA progression and near the end of life. Methods: We reviewed all cases of metastatic prostate cancer who received prescriptions for abi or enza from the New York VA (VA-NYHHS) from 6/2011-8/2017. We recorded patient demographics, laboratory/radiographic assessments, treatment, and rationale for treatment change. We calculated descriptive statistics, and used multivariable regression to identify factors associated with continuation of abi/enza, use in the last month of life, and survival. Results: Among 184 patients, 46% were white, 44% were black, 77% had bone metastases and the median age was 68. 74 patients received abi alone, 30 received enza alone, and 80 received both. Median PSA decrease on abi was 16.3 and median increase from nadir was 21.0 , with median continuation for 6 months beyond first PSA increase . 30 (19.5%) patients continued abi despite PSA increase > 50. Enza was continued for a median of 4 months beyond PSA progression, with 21 (20.2%) patients continuing beyond PSA increase > 50. Biochemical progression alone was the rationale for treatment cessation of 25 .7%, and 39.1% of patients receiving enza and abi respectively, while the remainder of treatment changes involved combined biochemical, radiographic and clinical changes. In multivariable logistic regression, older patients and black patients (HR: 0.41, CI 0.18-0.93) were less likely to receive a prescription within 1 month of death. In a Cox PH model, black race (HR2.21, CI 1.28-3.82) and receipt of med within 1 month of death (HR 9.39, CI 5.29-16.66) were associated with worse survival from abi/enza intiation, but continuation of abi beyond PSA change > 50 was not associated with improved survival. Of 37 (20.1%) patients who received abi/enza within 1 month of death 30% received treatment while on hospice services. Conclusions: A substantial number of patients continue enza/abi through large changes in PSA and within one month of death. The clinical benefit of therapy in these situations warrants additional study.
Development and pilot of brief surveys to evaluate the quality of coordinated, patient-centered cancer care.
Authors: Marcy Winget, Farnoosh Sheikhi, Steve Asch
Journal: Journal of Clinical Oncology (2016)

e18197 Background: Stanford Cancer Center is undertaking a Transformation Initiative with the over-arching goal of providing quality, patient-centered, coordinated care across the patient care continuum. A key goal is to remove the burden of coordinating care from the patient and place it on the Cancer Center. Here we describe the development and pilot testing of patient surveys used to assess change in patient experience over time. Methods: Domains and corresponding questions of patient-centered quality care were informed by the existing literature and existing tools available online, with a focus on domains relevant to cancer patients. Questions were modified as needed from validated or semi-validated instruments to have a consistent 4 or 5-category Likert response scale, put into four unique short instruments that included at most ten questions each and piloted in cancer clinic waiting rooms. Input from patients was sought to assess: 1) relevance and clarity of questions; 2) whether important concepts were missing; 3) acceptability for patients regarding the place and timing of the surveys and; 4) estimate top box scores. Internal consistency of the final question sets for each domain was examined using Cronbach’s alpha. Results: Patient feedback from the pilot was positive with respect to: ease and time in completing the instruments; relevance and clarity of questions; and appropriateness of time and place. Modifications to questions were made based on top box scores including creating a common 5-point Likert scale for all questions and excluding those with a top box score higher than 80%. An open comment field was also added which complements the quantitative responses. The Cronbach’s alpha for all domains was ≥ 0.80 expect for the access domain which was 0.51. The final four instruments have 7-8 questions each and take only a few minutes for patients to complete. Conclusions: The short surveys developed have been successfully implemented in the Stanford cancer clinics for about one year and continue to be acceptable and relevant to patients. Other cancer centers and their patients may benefit from similar short surveys.
Towards enhancing the specificity of precision medicine assays.
Authors: Donald Joseph Johann, Meeiyueh Liu, Adam Roberge, Kristen Noyes, Kennedy Sanders, Michael Emmert-Buck, Michael Tangrea
Journal: Journal of Clinical Oncology (2018)

e24170 Background: A methodology that accurately and efficiently captures tumor cells from patient specimens in a clinical workflow does not yet exist. Precision medicine will benefit from such an advance. Immunohistochemical staining (IHC) of histological sections is well-established for classifying tumors and may be used as a targeting strategy for procurement of labeled cells via tissue microdissection, including immuno-LCM, immuno/computer-LCM, expression microdissection, and other techniques. The antigen retrieval (AR) process employed at the beginning of most IHC protocols increases epitope availability and improves staining characteristics; however, the procedure can damage biomolecules (DNA, RNA) to an unknown extent. Methods: To better understand the effects of AR on DNA/RNA quality and quantity, model system samples (lung cancer PDX tissue) and clinical specimens (KRAS gene mutation positive cases) were subjected to commonly employed AR methods [heat induced epitope retrieval (HIER), protease digestion] and the effects on DNA were assessed by Qubit, Fragment Analyzer, agarose gels, kappa qPCR, ddPCR, and NGS targeted sequencing. Results: HIER resulted in optimal staining characteristics, but induced significant damage to DNA, producing extensive fragmentation and decreased yields. Variation in the HIER protocol mitigated but did not eliminate the negative effects. In contrast, the consequence of protease treatment on DNA were relatively minor and immunostaining quality was acceptable, although diminished in intensity compared to HIER treated sections. Apart from the AR procedure, the IHC process itself also resulted in a decreased yield of DNA. However, in spite of the deleterious effects on DNA, none of the AR methods combined with IHC negatively affected PCR amplification of small amplicons, and KRAS gene mutations were successfully identified in the clinical cases under all conditions. RNA work is in progress and results will be reported. Conclusions: Data indicate that DNA recovered from histology slides after standard AR and IHC processing can be successfully employed for the majority genomic applications. Importantly, studies that require larger DNA fragments such as long-read sequencing should avoid the use of HIER.
Downregulation of<i>Dipeptidyl Peptidase 4</i>Accelerates Progression to Castration-Resistant Prostate Cancer
Authors: Joshua W. Russo, Ce Gao, Swati S. Bhasin, Olga S. Voznesensky, Carla Calagua, Seiji Arai, Peter S. Nelson, Bruce Montgomery, Elahe A. Mostaghel, Eva Corey, Mary-Ellen Taplin, Huihui Ye, Manoj Bhasin, Steven P. Balk
Journal: Cancer Research (2018)

The standard treatment for metastatic prostate cancer, androgen deprivation therapy (ADT), is designed to suppress androgen receptor (AR) activity. However, men invariably progress to castration-resistant prostate cancer (CRPC), and AR reactivation contributes to progression in most cases. To identify mechanisms that may drive CRPC, we examined a VCaP prostate cancer xenograft model as tumors progressed from initial androgen sensitivity prior to castration to castration resistance and then on to relapse after combined therapy with further AR-targeted drugs (abiraterone plus enzalutamide). AR activity persisted in castration-resistant and abiraterone/enzalutamide-resistant xenografts and was associated with increased expression of the AR gene and the AR-V7 splice variant. We then assessed expression of individual AR-regulated genes to identify those that persisted, thereby contributing to tumor growth, versus those that decreased and may therefore exhibit tumor suppressor activities. The most significantly decreased AR target gene was dipeptidyl peptidase 4 (DPP4), which encodes a membrane-anchored protein that cleaves dipeptides from multiple growth factors, resulting in their increased degradation. DPP4 mRNA and protein were also decreased in clinical CRPC cases, and inhibition of DPP4 with sitagliptin enhanced the growth of prostate cancer xenografts following castration. Significantly, DPP4 inhibitors are frequently used to treat type 2 diabetes as they increase insulin secretion. Together, these results implicate DPP4 as an AR-regulated tumor suppressor gene whose loss enhances growth factor activity and suggest that treatment with DPP4 inhibitors may accelerate emergence of resistance to ADT.Significance: These findings identify DPP4 as an AR-stimulated tumor suppressor gene that is downregulated during progression to castration-resistant prostate cancer, warning that treatment with DPP4 inhibitors, commonly used to treat type 2 diabetes, may accelerate prostate cancer progression following androgen deprivation therapy. Cancer Res; 78(22); 6354-62. ©2018 AACR.