tbuckley/cabot-search huggingface dataset:
A multicenter analysis of patient reported risk factors for not working during cancer therapy.
Authors: Victoria Susana Blinder, Carolyn E. Eberle, Emeline Aviki, Stephen Matthew Schleicher, Sujata Patil, Ethan M. Basch, Jeff A. Sloan, Antonia Vickery Bennett
Journal: Journal of Clinical Oncology (2017)

6523 Background: Treatment for most types of cancer results in work disruptions. The aim of this study is to identify risk factors for not working during cancer therapy using a patient-reported outcome tool. Methods: Patients of all cancer types, who were undergoing treatment with curative or palliative intent, were enrolled in a survey-based study at Memorial Sloan Kettering Cancer Center and the North Carolina Cancer Hospital from 1/2014 to 7/2015. All patients working full- or part- time at the time of cancer diagnosis were included in this analysis. Patient reported outcomes were collected using a survey tool at any time during active cancer treatment. The primary outcome of this analysis was self-reported work status at the time of survey completion. Results: Of 119 patients who were working before their cancer diagnosis, 68% were working at the time of survey completion. The mean age was 52.9 (range 20-80). Younger age was associated with working: 82% of patients age &lt; 40 were working during treatment vs. 31% of patients age &gt; 65 (p=0.01). The number of days patients reported being completely unable to work in the past month was significantly associated with work status; only 26% of patients who missed &gt; 10 days continued to work compared to 69% who missed ≤ 10 days (p&lt;0.01). Patients who report having a flexible work schedule were 23% more likely to continue to work during treatment (69% vs. 46%, p=0.01). In a multivariable model controlling for having an employer contingent health plan, and household income &gt; 200% of the federal poverty level (fpl), only age, having a flexible work schedule, and inability to work &gt; 10 days were independently associated with work status during treatment (Table). Conclusions: Having a flexible work schedule allowed for more work interruptions without job loss. Patients who are likely to miss more than 10 days of work and who have inflexible work schedules are at high risk of unemployment and should be targeted for employment retention initiatives. [Table: see text]
The financial impact of hypofractionated radiation for prostate cancer.
Authors: Assaf Moore, Ido Stav, Robert Benjamin Den, Michal Sarfaty, Victoria Neiman, Eli Rosenbaum, Daniel A. Goldstein
Journal: Journal of Clinical Oncology (2018)

6613 Background: Until recently, dose intensified radiotherapy with 1.8-2 Gy fractions was the standard radiation method for prostate cancer. Multiple studies have demonstrated similar efficacy and tolerability with moderate hypofractionation (2.5-3 Gy per fraction). In recent years there has been an increasing focus placed on understanding the cost and value of cancer care. The objective of this study was to assess the societal economic impact of treating localized prostate cancer in the United States (US) with moderate hypofractionation vs standard fractionation. Methods: We calculated the national annual target population of patients treated with definitive external beam radiotherapy using the Surveillance, Epidemiology, and End Results (SEER) database. Treatment costs for various fractionation schemes were based on billing codes and 2018 pricing by the Centers for Medicare and Medicaid Services (CMS). Results: We estimate that 28,500 patients with localized prostate cancer are treated with radiotherapy annually in the US. The cost of standard fractionation in 45 or 39 fractions is US$ 26,782 and 23,625 per patient, respectively. With moderate hypofractionation in 28 or 20 fractions, the cost is US$ 17,793 and 13,402 per patient, respectively. The use of moderate hypofractionation would lead to 24.7-50% annual savings of $US 166,147,848 – 381,128,820 in the United States. Conclusions: Moderate hypofractionation may have the potential to save approximately US$ 0.16-0.38 billion annually in the United States, likely without impacting survival or tolerability. Depending on insurance provider, this option may lead to lower personal financial toxicity. It would be reasonable for public and private payers to consider providing reimbursement only for moderate hypofractionation.
<i>PBRM1</i> mutation and immunotherapy efficacy: A comprehensive genomic profiling (CGP) assessment.
Authors: Gennady Bratslavsky, Laurie M. Gay, Ethan Sokol, Julia Andrea Elvin, Jo-Anne Vergilio, James Suh, Shakti H. Ramkissoon, Sugganth Daniel, Eric Allan Severson, Jonathan Keith Killian, Siraj Mahamed Ali, Jon Chung, Alexa Betzig Schrock, Garrett Michael Frampton, David Fabrizio, Vincent A. Miller, Muhammad Raza Naqvi, Mehdi Mollapour, Robert John Corona, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2018)

12091 Background: PBRM1, a member of the SWI/SNF family, is involved in chromatin remodeling. Recent evidence indicates that PBRM1 inactivating mutations are associated with clinical benefit from immune checkpoint inhibitor treatments in clear cell renal cell carcinoma (ccRCC). Methods: CGP was performed on 140,411 specimens from solid tumors and hematologic malignancies using a hybrid capture-based NGS assay. Profiles were assessed for neoantigen load, tumor mutational burden (TMB), determined on 1.1 Mbp of sequenced DNA, and microsatellite instability (MSI) determined by principal components analysis of optimal homopolymer loci. Genomic alterations (GA) in PBRM1 considered here were known loss-of-function GA or homozygous GA in the tumor. Results: PBRM1 GA were identified in 3,674 (2.6%) cases. Compared to other tumor types, the PBRM1 GA frequency was significantly higher in ccRCC at 45% (P < 0.0001); other tumor types with frequent PBRM1 GA were renal cell carcinoma NOS (27%), site-specific mesothelioma (MESO) (7-20%), cholangiocarcinoma (CCA) (12%), and chordoma (11%). PBRM1 GA were found in < 3% of highly prevalent tumors, including melanomas, carcinomas of lung, breast, colon and prostate, and all hematolymphoid malignancies. For ccRCC the most common co-altered genes with PBRM1 were VHL (80%), SETD2 (31%), KDM5C (15%), PTEN and TP53 (13%), TSC1 and CDKN2A (7%), TERT, PIK3CA, BAP1 and CDKN2B (6%) and MTOR (5%). Top co-mutated genes in other tumors were BAP1 (84%) and NF2 (27%) in MESO; ARID1A (33%) and IDH1 (30%) in CCA; and PTEN (11%) and CDKN2A (8%) in chordoma. Median TMB for PBRM1-mutated ccRCC was 2.5 mutations (mut)/Mb, with only one highly mutated sample (MSI-High and TMB ≥20 mut/Mb). These results were similar for PBRM1 WT ccRCC (median 2.6 mut/Mb; no MSI-High or TMB ≥20 mut/Mb). Neoantigen load in ccRCC is significantly associated with PBRM1 GA positivity (p < 0.02), but not TMB (p < 0.50). Conclusions: This study confirms PBRM1 GA are significantly enriched in ccRCC, an immunotherapy responsive tumor type lacking high MSI or TMB. Further study of PBRM1 GA in both renal and non-renal malignancies appears warranted, including evaluation of co-occuring GA that may predict ICPI efficacy.
Aspirin use and survival in head and neck squamous cell cancer (HNC) patients.
Authors: Hind Rafei, Catherine Lumley, Jim Han, Thomas M. Kaffenberger, Jessica H. Maxwell
Journal: Journal of Clinical Oncology (2017)

6042 Background: The phosphatidylinositol-3-kinase (PI3K) signaling pathway is the most common genetic alteration in HNC, particularly in oropharynx cancers (OPC). Up-regulation of the PI3K pathway enhances the production of prostaglandins inhibiting apoptosis in cancer cells. We hypothesized that aspirin (ASA) improves survival in HNC patients (pts) by counteracting the effects of prostaglandins. Methods: This is an IRB-approved retrospective cohort study of 584 veterans with HNC treated at the Washington DC Veterans Affairs Medical Center between 1995 and 2015. Charts were reviewed for clinical-pathologic and treatment data; recurrence/distant metastases; cause of death; and for the number, date and dose of ASA prescriptions. Pts who filled more than one prescription, excluding refills, after diagnosis of HNC were considered ASA users. All others were considered non-ASA users. The Kaplan-Meier method and log-rank test were used to compare disease-free survival (DFS) and disease-specific survival (DSS) between users and non-users. Results: 332 pts met inclusion criteria. Primary subsites included oropharynx (n = 146), larynx (n = 105), oral cavity (n = 62), and hypopharynx (n = 19). 86 pts were ASA users after diagnosis (25.9%) and more likely to be older (p = 0.002), African American (p = 0.03), never-alcohol users (p = 0.044), and have early stage cancer (I/II; p &lt; 0.0005) compared to non-ASA users. Among all HNC pts, ASA users demonstrated significantly better 5-year (y) DSS (82%) compared to non users (43%; p = 0.009). 5-y DFS was also significantly higher among users (72%) vs non users (39%; p &lt; 0.001). Among the OPC pts, 5-y DSS was higher for ASA users (74%) vs non users (41%; p = 0.024). 5-y DFS was also better for users (72%) vs non users (39%; p = 0.004). For stages III and IV, 5-y DFS was significantly higher among ASA users (64%) vs non users (44%; p = 0.035). 5-y DSS was higher as well in users (69%) vs non users (44%) but p = 0.098. On multivariate analysis, aspirin use remained an independent prognostic factor associated with improved DSS and DFS when accounting for age, race, gender, subsite, stage, tobacco and alcohol use. Conclusions: Aspirin use following diagnosis and curative treatment of HNC is associated with improved DSS and DFS.
Acute care use among women receiving adjuvant chemotherapy for breast cancer.
Authors: Kathryn Jean Ruddy, Lindsey R. Sangaralingham, Rachel A. Freedman, Ahmedin Jemal, Carrie A. Thompson, Shahrukh K. Hashmi, Sarah Schellhorn Mougalian, Cary Philip Gross, Nilay D. Shah
Journal: Journal of Clinical Oncology (2016)

6543 Background: Doxorubicin-cyclophosphamide (AC), docetaxel-cyclophosphamide (TC), and AC followed by or preceded by docetaxel or paclitaxel (ACT) are common adjuvant chemotherapies for early stage breast cancer. We aimed to assess how adjuvant AC, TC, and ACT differ with regard to early and later acute care use, both of which may be surrogates for severe toxicity. Methods: We utilized administrative claims data from a large U.S. commercial insurance database (OptumLabs) to retrospectively identify privately insured and Medicare Advantage-insured women with early stage breast cancer who received adjuvant AC, TC, or ACT during 2005-2013 (using validated claims-based algorithms). We analyzed billing data 0-6 and 6-12 months after the first dose of chemotherapy to examine rates of hospitalizations and emergency room (ER) visits. We used Poisson regression models to calculate rates of acute care use adjusted for age, race, and Charlson comorbidity score at diagnosis. Results: We identified 4,501 patients; 1,785 received TC, 644 AC, and 2,072 ACT. Average age at diagnosis was 53 years. Overall, 17% were hospitalized and 21% were seen in the ER without a subsequent hospitalization within 12 months of the start of the chemotherapy. In total, there were 983 hospitalizations and 1281 ER visits in this population. Please see the Table for differences between regimens in acute care use. Conclusions: Patients who receive adjuvant AC, TC, and ACT for breast cancer have different needs for acute care. This may reflect treatment assignment bias or unequal risks of severe toxicity. Further characterization of these events may help inform treatment decisions. Adjusted hospitalizations and ER visits per 100 patients. Care Type AC TC ACT Hospitalization 0-6 months 17.7 11.1 11.8 Hospitalization 6-12 months 13.8 19.9 18.8 ER visit 0-6 months <1 5.7 8.6 ER visit 6-12 months 8.0 7.5 7.8
Prognostic value of the metastatic lymph node (N) ratio in the adjuvant chemoradiotherapy in stomach tumors (ARTIST) phase III trial
Authors: Soonil Lee, Se Hoon Park, Jeeyun Lee, Won Ki Kang
Journal: Journal of Clinical Oncology (2016)

4038 Background: The proportion between metastatic and examined lymph nodes (N ratio) has been proposed as an independent prognostic factor in gastric cancer (GC) patients. The aim of this study is to investigate the relationship between the metastatic N ratio and the prognosis of GC after curative D2 surgery Methods: We retrospectively reviewed the data of 458 ARTIST patients who underwent D2 gastrectomy followed by adjuvant chemotherapy with capecitabine plus cisplatin (XP, n = 228) or chemoradiotherapy (XPRT, n = 230). Disease-free survival (DFS) of the patients was analyzed in order to evaluate the influence of N ratio on treatment outcome. Four N ratio categories (0% v 1-9% v 10-25% v > 25%) were employed, and statistical analysis was performed using adjusted Cox regression and stratified survival analysis. Results: Among 458 GC patients enrolled in ARTIST, the proportion of patients with at least 15 lymph nodes examined was 99%. As expected, there was a significant interaction between the N staging and N ratio. At multivariate analysis, N ratio was retained as an independent prognostic factor for DFS: HR for N ratio 0%, 1; N ratio 1-9%, 1.061; N ratio 10-25%, 1.202; and N ratio > 25%, 3.571. Furthermore, there also was a significant difference in DFS between XPRT and XP arms for patients with higher N ratio. In patients with N ratio > 25%, the 5-year DFS was 55% v 28% for XPRT and XP arms, respectively (HR, 0.527; 95% CI, 0.307 to 0.904; P = 0.020). Conclusions: In patients with curatively resected GC, N ratio is independently associated with DFS. Although this finding warrants further investigation in prospective studies, benefit with chemoradiotherapy in D2 resected GC seems to be limited to those with N ratio > 25% Clinical trial information: NCT00323830.
Patient and tumor-related factors for sphincter-preserving surgery in patients with rectal cancer.
Authors: Faisal Shahjehan, Dorin Colibaseanu, Kellie L. Mathis, Pashtoon Murtaza Kasi, Amit Merchea
Journal: Journal of Clinical Oncology (2018)

e15628 Background: Sphincter-preserving surgery (SPS) is associated with better quality of life in post-surgical rectal cancer patients. We aimed to report the factors that determined the likelihood of undergoing SPS. Methods: We retrospectively analyzed 36,448 rectal cancer patients for rate, pattern and survival of SPS. Characteristics of rectal cancer patients undergoing SPS and non-SPS diagnosed from 2004-2012 from the National Cancer Database (NCDB). Normally distributed data was assessed with Student’s t test and non-normally distributed data with Mann-Whitney U test. SPS trends were estimated using Cochrane-Armitage trend test. Cox proportional hazard model was used to calculate hazard ratios for outcome death. Odds ratios were calculated using logistic model for outcome SPS. Survival analysis of patients having SPS and non-SPS was performed using the Kaplan-Meier method. A p-value < 0.05 was set statistically significant. Results: 27,832 (76%) patients had SPS. Majority of SPS patients were aged < 70 (73%), had private insurance (51.6%) and got treatment at comprehensive community cancer program (53.7%). Multivariate analysis showed that patients with age ≥70 (OR 0.89, 95% CI: 0.83 – 0.95), male gender (OR 0.91, 95% CI: 0.86 – 0.95), having Medicare (OR 0.83, 95% CI: 0.78 – 0.89), Medicaid (OR 0.74, 95% CI: 0.67 – 0.83), and poorly differentiated histology (OR 0.81, 95% CI: 0.75 – 0.87) were less likely to undergo SPS. Compared to non-SPS, SPS patients had better 5-year overall survival (73% vs 66%). Univariate analysis showed that patients having non-SPS have higher likelihood of mortality than SPS (HR 1.37, 95% CI: 1.31 – 1.44). Conclusions: We were able to identify several patient and tumor-related factors impacting the likelihood of undergoing SPS. Patients undergoing SPS had better overall survival than non-SPS.
Variation and Trends in Antidepressant Prescribing for Men Undergoing Treatment for Nonmetastatic Prostate Cancer: A Population-based Cohort Study
Authors: Rano Matta, Christopher J.D. Wallis, Mitchell G. Goldenberg, Amanda E. Hird, Zachary Klaassen, Girish Kulkarni, Ronald T. Kodama, Sender Herschorn, Robert K. Nam
Journal: European Urology (2018)
Prospective registration of cancer clinical trials in India.
Authors: Sean Butterbaugh, Arya Mariam Roy, Hassan Hasanein, Reema Anil Patel, Aju Mathew
Journal: Journal of Clinical Oncology (2018)

e18863 Background: The Clinical Trials Registry of India (CTRI), launched in July 2007, was established to bring transparency and accountability to clinical trials performed in India. Mandatory registration of clinical trials was required from June 2009. However, trials were not required to be registered prospectively, before a patient was recruited. Prospective registration of trials is an index of the quality of trial infrastructure and is important to avoid selective reporting of favorable results and non-reporting of unfavorable results. We conducted an audit on cancer clinical trials registered in CTRI to estimate compliance with prospective registration. Methods: We conducted a descriptive survey of all cancer clinical trials registered in India by performing a search in the CTRI registry. Data from the registry’s inception in 2007 through May 8, 2017 were collected. 559 clinical trials were identified. Results: Out of the 559 cancer clinical trials registered in CTRI, only 247 (44%) were done prospectively. Remaining 312 trials were either registered retrospectively (34%) or no information on trial registration was provided by the investigators (22%). Of the 312 trials that were not registered prospectively, 25% were done as part of a post-graduate thesis (vs 15% trials registered prospectively) and 60% were interventional trials. Pharmaceutical industry sponsored 39% of the 312 trials that were not registered prospectively (vs 55% in prospectively registered trials), and 31% was supported by the government (vs 29%). An academic investigator served as the PI in 62% of trials that were not reported prospectively (vs 47%). Trials that were sponsored by pharmaceutical industry (n = 257) were more likely to be completed (43% vs 27% in non-pharmaceutical funded trials) and prospectively registered (53% vs 37%). Conclusions: In our audit of cancer clinical trials in India, we observed low rate of prospective trial registration. Pharmaceutical funded trials were more compliant with CTRI guidelines. The CTRI has now mandated prospective trial registration from April 1st, 2018. Trials will be required to be registered in CTRI prior to patient recruitment. In our opinion, this mandate will considerably improve the quality of cancer clinical trials in India.
Telmisartan and thiorphan combination treatment attenuates fibrosis and apoptosis in preventing diabetic cardiomyopathy
Authors: Vajir Malek, Anil Bhanudas Gaikwad
Journal: Cardiovascular Research (2018)

LCZ696, a first-generation dual angiotensin receptor-neprilysin inhibitor (ARNi), is effective in treating heart failure patients. However, the role of ARNis in treating diabetic cardiomyopathy is poorly understood. This study evaluates the efficacy of a novel combination of telmisartan [angiotensin receptor blocker (ARB)] and thiorphan [neprilysin inhibitor (NEPi)] in ameliorating diabetic cardiomyopathy while, at the same time, exploring the relevant underlying molecular mechanism(s).Diabetes was induced by administration of streptozotocin (55 mg/kg, i.p.) in male Wistar rats. After 4 weeks, diabetic rats were subjected to either thiorphan (0.1 mg/kg/day, p.o.) or telmisartan (10 mg/kg/day, p.o.) monotherapy, or their combination, for a period of 4 weeks. Metabolic and morphometric alterations, failing ventricular functions, and diminished baroreflex indicated development of diabetic cardiac complications. Apart from morphometric alterations, all pathological consequences were prevented by telmisartan and thiorphan combination therapy. Diabetic rats exhibited significant modulation of the natriuretic peptide system, a key haemodynamic regulator; this was normalized by combination therapy. Histopathological studies showed augmented myocardial fibrosis, demonstrated by increased % PSR-positive area, with combination therapy giving the best improvement in these indices. More importantly, the combination of thiorphan and telmisartan was superior in attenuating inflammatory (NF-κB/MCP-1), profibrotic (TGF-β/Smad7) and apoptotic (PARP/Caspase-3) cascades compared to respective monotherapies when treating rats with diabetic cardiomyopathy. In addition, diabetic heart chromatin was in a state of active transcription, indicated by increased histone acetylation (H2AK5Ac, H2BK5Ac, H3K9Ac, and H4K8Ac) and histone acetyltransferase (PCAF and Ac-CBP) levels. Interestingly, combination treatment was sufficiently potent to normalize these alterations.The protective effect of novel ARB and NEPi combination against diabetic cardiomyopathy can be attributed to inhibition of inflammatory, profibrotic, and apoptotic cascades. Moreover, reversal of histone acetylation assists its protective effect.
Synectin gene disruption produces global vascular defects that associate with impaired cardiac function in adult mice.
Authors: Thomas W. Chittenden, Anthony A Lanahan, M Drinane, Zhen W Zhuang, K Moodie, E DeMunick, A Helisch, Robert T Palac, Mary Jo Mulligan-Kehoe, Eduard Dedkov, Robert Tomanek, Michael Simons
Journal: Circulation (2004)
Results of a pan-Canadian approach to systems change for smoking cessation support in Canadian cancer centers.
Authors: Michelle Halligan, Deb Keen, Caitlyn Timmings, Graham W. Warren
Journal: Journal of Clinical Oncology (2018)

e18538 Background: Smoking cessation even after a cancer diagnosis can improve survival, but access to smoking cessation support is limited. The purpose of this abstract is to describe results from a systems change approach by the Canadian Partnership Against Cancer (CPAC) to promote adoption of evidence-based cessation within provincial and territorial cancer systems across Canada. Methods: Beginning in 2015, an initiative was developed to convene a meeting of all Canadian provinces and territories to apply for 15 months of CPAC funding that could be used to support planning, implementation, and evaluation of smoking cessation services in the ambulatory cancer care setting. CPAC resources were used to support sustainable system change related to smoking cessation, including: executive champions, project leads, monthly teleconference calls, cross-project evaluations, in-person knowledge exchange workshops, and common-core elements for planning, dissemination, and reporting to support adoption and implementation. Results: In 2016, ~$1.0M (USD) was provided to 7 provinces and 2 territories. Funds were used for primary projects related to planning (2 provinces and 2 territories), implementation (3 provinces), and evaluation (2 provinces). After 15-months of funding from CPAC, 6 provinces reported implementation of smoking cessation for ambulatory cancer patients. The remaining province and 2 territories funded by CPAC reported development of plans for adoption of smoking cessation for cancer patients in the future. Within provinces reporting implementation of smoking cessation for cancer patients, between 65-97% of ambulatory cancer patients were screened for smoking status; 22-80% of patients who reported smoking were offered a referral to cessation services, and 21-45% of cancer patients accepted a referral. Conclusions: Assisting local clinical authorities to address tobacco use in the cancer care setting can result in significant systems change within a relatively short period of time. Support for sustained adoption and scaling of efforts to adopt smoking cessation as a therapeutic intervention for cancer care are planned.