tbuckley/cabot-search huggingface dataset:
Cost effectiveness of surveillance for distant recurrence in extremity soft tissue sarcoma.
Authors: Trevor Joseph Royce, Rinaa S. Punglia, Sagar Anil Patel, Katherine Anne Thornton, Chandrajit P. Raut, Elizabeth H. Baldini
Journal: Journal of Clinical Oncology (2017)

11021 Background: Optimal surveillance strategies for extremity soft tissue sarcoma (STS) are unknown. We performed a cost-effectiveness analysis of competing imaging modalities performed at National Cancer Comprehensive Network guideline-specified intervals. Methods: We developed a Markov model simulating lifetime outcomes for 54-year-old patients after definitive treatment for Stage II-III extremity STS using four surveillance strategies: watchful waiting (WW), chest x-ray (CXR), chest computed tomography (CCT) and positron emission tomography-computed tomography (PET/CT) performed every 3-6 months for the first 3 years, every 6 months until year 5, and then annually. We used probabilities, utilities and costs extracted from the literature and Medicare claims to determine incremental cost-effectiveness ratios (ICER). Results: While the model showed that CCT is the most effective strategy, CXR is the most cost-effective strategy at a societal willing-to-pay (WTP) of $100,000/quality-adjusted life year (QALY). The ICER is $14,306/QALY for CXR versus $117,683/QALY for CCT while PET/CT is never cost effective (Table). Sensitivity analyses demonstrated CCT becomes the preferred imaging modality as the lifetime risk of DR increases beyond 38% or as the societal WTP increases beyond $130,000/QALY. Conclusions: Optimal DR surveillance imaging for Stage II-III extremity STS should be individualized based on patients’ risks for DR. CXR, or CCT at more protracted intervals, may be preferred for lower risk patients (i.e. DR risk less than 38%), whereas CCT may be preferred for higher risk patients (i.e. DR risk greater than 38%). These findings can help refine guidelines to reduce resource overutilization during surveillance of sarcoma patients. [Table: see text]
Immune sidedness of breast cancer: Pilot study of neutrophil/lymphocyte ratio anatomic disparities in breast cancer patients.
Authors: Zachary Spigelman
Journal: Journal of Clinical Oncology (2018)

e13094 Background: Elevated Neutrophil/Lymphocyte ratios (NLR) have been associated with increased mortality in breast cancer and other solid tumors and a negative predictor of sensitivity to checkpoint inhibitor therapy. A Metaanalysis of 15 studies and 8563 breast cancer patients by Ethier et al(Breast Cancer Research 2017;19: 2) revealed a NLR greater than 3 was associated with a worse OS (HR2.56, 95% CI = 1.96) In light of the recent discovery by Venook et al in CALGB/SWOG 80405 of differences in response rates to cetuximab in colon cancer depending on anatomic “Sidedness”, we questioned whether there was a similar phenomenon of “Sidedness” occurring in breast cancer patients. Methods: Using NLR as a predictor, 301 breast cancer patients in the Parkland Hospital tumor registry diagnosed between 2013-2018 were evaluated. Anatomic quadrant position of initial breast cancer diagnosis was correlated with a concurrent assessment of the patient’s NLR. Of the initial 301 patients, 155 patients were determined to have assessable data. 79 patients with left sided breast cancer and 76 with right-sided breast cancer. Patients with an NLR of greater than 3 were determined to be a positive result. Chi Square and P values were calculated comparing left and right breast NLRs and their respective quadrant NLRs. Results: Patients Neutrophil/Lymphocyte ratios greater than 3.0 were found in 30 of 79 left sided breast cancers and 41 of 76 right-sided breast cancers. ((P value 0.046). Left upper outer quadrant breast cancers were found to have 10 of 36 cancers with NLR greater than 3, while Right upper outer quadrant cancers had 25 of 47 NLRs greater than 3. (P value 0.020) Conclusions: NLR’s of greater than 3 were significantly more frequent in left sided breast cancers than right sided breast cancers. There may an intrinsic sidedness to breast cancer disease or breast immune function. Neoantigen formation, anatomic spatial relationship to the thoracic duct or lymph nodes, or possibly differences in ontogenetic tissue development may account for some of the NLR sidedness. Such findings warrant further study by larger data sets.
Non-examination of lymph nodes (LN) and overall survival (OS) in non-small cell lung cancer (NSCLC) patients.
Authors: Ahmedin Jemal, Chun Chieh Lin, Matthew Smeltzer, Raymond U. Osarogiagbon
Journal: Journal of Clinical Oncology (2016)

8547 Background: Theoretically, NSCLC patients without LN examination are more likely to be understaged and undertreated. We compared the OS of NSCLC patients without pathologic (p) LN examination (pNx) to that of patients with pLN examination but no LN metastasis (pN0) and patients with hilar/intrapulmonary LN metastasis (pN1). We also examined whether postoperative adjuvant therapy could improve OS in patients with pNx. Methods: Patients had resection for stage I-IIIA NSCLC from 2004-2011 in the National Cancer Data Base. OS was estimated by the Kaplan-Meier method and compared using log-rank tests stratified by pN status. Cox proportional hazards model was used to compare OS, adjusted for patient sociodemographic and clinical characteristics, treatment, and provider characteristics. Results: Of 97,794 patients, 79.5% were pN0, 14.6% were pN1, and 5.9% were pNx. pNx patients had similar sociodemographic and clinical characteristics to pN0 patients, except they were more likely to be older, Medicare insured and have more comorbidity. While 77% of pNx patients had sublobar resection, 87% of pN0 and 95% of pN1 patients had lobectomy or greater. pNx patients had similar likelihood of receiving adjuvant therapy as pN0 patients (14.4% vs 12.3%). 5-year OS rates were: 65% (pN0) vs. 47% (pNX) vs. 44% (pN1) (log-rank p < .0001) in all patients; and 66% (pN0) vs. 53% (pNX) vs. 44% (pN1) (log-rank p < .0001) in patients with lobectomy or greater resection. The OS difference was consistent across all T categories. After adjusting for patient demographic, clinical and provider characteristics, adjuvant chemotherapy for pNx patients was not associated with survival, irrespective of tumor size (p = 0.31). Conclusions: NSCLC patientswithout LN examination were more likely to have received sublobar resection. They had lower OS compared to patients with LN examination. Adjuvant therapy did not improve their OS. Proper LN examination should be emphasized across all lung cancer programs to ensure the highest quality of lung cancer surgery to all patents.
Benefits of satellite lab in the reduction of chemotherapy waiting time.
Authors: Abdullah Ahmed Bany Hamdan, Jesusa Christine Tamani, Sheena Peethambaran, Isamme Alfayyad, Richard Erlandez, Huda Abdullah Abdulkarim, Mona Hussein, Mushabbab AlAsiri, Musa AlHarbi
Journal: Journal of Clinical Oncology (2017)

e18218 Background: Oncology patients need to receive their course of treatment in a timely manner. Increasing the efficiency of laboratory testing could potentially improve hospital operations and thus have a positive impact on patient care. One way of doing this is by initiating an installation of a satellite laboratory. The purpose of this study is to determine the advantages of having a satellite laboratory in an oncology unit. Moreover, it shall also try to determine whether the presence of satellite laboratory will help reduce the chemotherapy waiting time of oncology patients. Methods: This study utilized experimental study design in order to analyze and compare Laboratory Turnaround time (TAT) and the chemotherapy waiting time before and after establishment of satellite laboratory. The samples taken as base line data was 150 and compared to samples taken from 2013-2015. The population of this study included patients in Comprehensive Cancer Center of King Fahad Medical City diagnosed with cancer and received chemotherapy regardless of their age and sex. Results: Laboratory Mean TAT decrease significantly from 1 hour and 30 minutes in 2012 to 43 minutes, 43 minutes, and 37 minutes in 2013, 2014 and 2015 respectively. Also chemotherapy Mean waiting time decreased from 2012 base line of 252 to 164 minutes in 2013, 115 minutes in 2014 and 146 minutes in 2015. The chemotherapy waiting time shows a decreasing pattern as the laboratory time decrease from 2013 to 2015. This shows that there is a decrease in the chemotherapy time and turnaround time before and after the intervention. We also have identified that there is a direct relationship between the reduction of turnaround time and chemotherapy waiting time. Conclusions: The need to structure how we deliver patient care specifically to cancer patient is an important drive for quality improvement. Basing on the result of the project and with the increase in patient satisfaction rate, it can be concluded that it is possible to reduce patients’ mean chemotherapy waiting time by applying more efficient process, which is the installation of satellite laboratory.
The ARCAD METACER national cohort study of brain metastases in gastro-intestinal cancers.
Authors: Fabienne Portales, Olivier Bouche, Simon Thezenas, Marie-Line Garcia, F Huysman, May Mabro, Isabelle Deleruyelle, Eric Terrebonne, Claire Garnier-Tixidre, Christophe Louvet, Thierry Andre, Thomas Aparicio, Olivier Dubreuil, Helene de Forges, Malika Attia, David Tougeron, Marc Ychou
Journal: Journal of Clinical Oncology (2016)

2073 Background: Brain metastases (BM) are quite rare and not well-documented in gastro-intestinal (GI) cancers. This prospective multicenter cohort study aimed to assess the overall survival (OS) in GI cancer patients with BM. Methods: From 2012 to 2014, 147 patients with synchronous or metachronous BM from histologically-proven GI primary tumors (PT) from 15 French centers were included. OS was defined as the time from BM diagnosis until death. Results: Patients were mainly women (64.6%); median age was 65.5 [28-92]. Histology was adenocarcinoma in 138 pts (95.8%). PT sites were mainly colorectal (71.9%), gastroesophageal (GE) (17.1%), biliary tract (7.6%). Initial staging was T3-T4 in 87 pts (65.5%), positive nodal status in 74 pts (55.2%). 61 pts (44.5) were M0, 75 pts (55.6%) were metastatic with 1, 2 or 3 sites in 42.2%, 36.3% and 21.5 %. Extra-cerebral metastases (ECM) were mostly lung (63.7%) and liver (59.3%). Median time between PT diagnosis and BM occurrence was 25.9 months [1.3-243.2]. 89 pts (60.5%) had PT or ECM progression. BM were unilateral in 62.5% patients, cerebral, cerebellar or both in 59.3%, 12.1% and 28.6%, respectively. BM management was anti-oedematic agents in 120 pts (84.5%), surgery in 25 pts (17.6%), whole-brain or stereotaxic radiotherapy in respectively 78 (54.1%) and 23 pts (16.0%). After a median follow-up of 28.7 months [0-32], median OS was 6.6 months [4.5-8.3]. Median OS was significantly higher in patients who underwent BM surgery, 12.1 (95%CI: 7.2-18.0) vs 4.6 (95%CI: 3.6-7.2) months (p= 0.010), in patients with WHO performance status 0-1 (8.4; 95%CI: 6.6-11.3) vs 2 (3.3; 95%CI: 2.4-5.9) (p= 0.001), and for cerebral (8.7; 95%CI: 5.9-12.3) vs cerebellar (4.6; 95%CI: 1.3-7.2) vs both (3.7; 95%CI: 2.4-7.5) localization (p= 0.013). In multivariate analysis, only BM localization was a significant prognostic factor for OS (HR = 1.7 and 1.8 for cerebellar and both localizations, p= 0.0168). Conclusions: Our study confirms that BM surgery improves poor survival of GI cancer patients with BM. Management and treatment of BM should be discussed in multidisciplinary meetings in regards of the prognostic factors identified, especially BM localization and PS. Authors thank the GERCOR for operational support.
Night shift work duration and risk of colorectal cancer according to IRS1 and IRS2 expression.
Authors: Yan Shi, Li Liu, Reiko Nishihara, Tsuyoshi Hamada, Mingyang Song, Daniel Nevo, Keisuke Kosumi, Mancang Gu, Kana Wu, Marios Giannakis, Yanan Ma, Jonathan Nowak, Andrew T. Chan, Charles S. Fuchs, Jeffrey A. Meyerhardt, Edward Giovannucci, Guanghai Dai, Eva S Schernhammer, Shuji Ogino, Xuehong Zhang
Journal: Journal of Clinical Oncology (2018)

3571 Background: Although accumulating evidence supports an association between night shift work and an increased risk of colorectal cancer (CRC), the mechanism remains elusive. Notably, metabolic disorders, including insulin resistance, play an important role in both CRC development and other chronic diseases caused by circadian disruption. IRS1 (insulin receptor substrate 1) and IRS2 are the primary mediators of insulin-dependent mitogenesis and could respond to the metabolic microenvironment. We therefore hypothesized that the risk of CRC in night shift workers might be different according to IRSs expression level. Methods: Among 77,470 eligible women with available night work data in the Nurses’ Health Study, we documented a total of 1,397 physician-confirmed CRCs during 24 years of follow-up, of which 304 and 308 had available data on IRS1 and IRS2, respectively. We used duplication method Cox proportional hazards regression analysis for competing risks data to calculate age-adjusted and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each CRC subtype. We measured tumor IRS1 or IRS2 protein expression by immunohistochemistry. Results: Compared with women who never worked night shifts, those working a rotating night shift for 15 years or more had a trend of increased overall risk of CRC [Ptrend= 0.06, multivariable HR = 1.20, 95%CI, 0.99 to 1.45]. For the same comparison, longer of night shift duration was associated with a higher risk of IRS1-positive tumors (multivariable HR = 1.81, 95%CI 0.94 to 3.48, Ptrend= 0.06) but not with IRS1-negative tumors (multivariable HR = 1.13, 95%CI 0.71 to 1.80, Ptrend= 0.56, Pheterogeneity for IRS1 subtypes = 0.02). The corresponding multivariable HRs were 2.69 for IRS2-positive tumors (95%CI 1.48 to 4.89, Ptrend= 0.001) and 0.90 for IRS2-negative tumors (95%CI 0.54 to 1.51, Ptrend= 0.72, Pheterogeneity for IRS2 subtypes = 0.008). Conclusions: Working 15 years or more of rotating night shift was associated with higher risk of CRC with IRS1-positive or IRS2-positive, but not negative tumors. This molecular pathological epidemiology data suggest a potential role of insulin receptor substrate in mediating carcinogenesis induced by night shifts.
Effect of nivolumab therapy on pulmonary artery.
Authors: Ludovic Fournel, Jennifer ARRONDEAU, Pascaline Boudou-Rouquette, Frederique Girault, Marie-Pierre Revel, Audrey Mansuet-Lupo, Nicolas Roche, Diane Damotte, Francois Goldwasser, Marco Alifano
Journal: Journal of Clinical Oncology (2017)

e18266 Background: Nivolumab, a human antibody targeting programmed death 1 receptor, is part of the armamentarium of lung cancer. Serious treatment-related adverse effects have been reported, including pneumonitis, whose mechanism is unclear. The aim of this study was to evaluate the occurrence of subclinical or patent pulmonary hypertension in patients receiving Nivolumab for advanced lung carcinoma. Methods: Clinical and morphometric data of patients receiving Nivolumab for treatment of advanced lung carcinoma are prospectively collected in our Institution and reviewed monthly by a multidisciplinary panel. For the purposes of the study, a blinded analysis of computed tomography (CT)-scans was performed, by two radiologists, to measure pulmonary artery (PA) and ascending aorta (Ao) diameters at the level of the bifurcation. Pre- and post-treatment PA/Ao ratios were calculated. Results: There were 62 patients with mean age and body mass index of 62.3 years and 24.3 kg/m 2 , all current or former smokers. Main histological type of carcinomas (stage IV in all cases) was adenocarcinoma (58.1%). Mean PA (+SD) diameters (before and after 4 cycles of Nivolumab [3mg/Kg]) were 26.3 (+/-2.8) mm and 28.0 (+3.0) mm, respectively (p = 4.9*10 -7 ). Mean Pre- and post-treatment by Nivolumab PA/Ao ratios were 0.82 (+0.09) and 0.87 (+0.11), respectively (p &lt; 0.001). There was no significant change in CT-scan aspect of lung parenchyma. Two patients experienced acute respiratory failure at day 52 and 58 after starting of Nivolumab therapy. CT-scan ruled out pulmonary embolism, but we observed PA/Ao ratio &gt; 1 suggesting acute pulmonary hypertension, confirmed by echocardiography. They both died despite intensive care. Even excluding these 2 patients from comparative analysis, PA diameters and PA/Ao ratios remain significantly higher after Nivolumab treatment (both p &lt; 0.001). Conclusions: Nivolumabcan induce subclinical or symptomatic acute pulmonary hypertensionpossibly leading to fatal adverse events.
Simultaneous EGFR mutation detection and copy number assessment in circulating tumour DNA (ctDNA) to inform molecular methods of therapy resistance and plasma ctDNA content in lung adenocarcinoma.
Authors: Alexandra Pender, Sareena Rana, Isaac Garcia-Murillas, Ros Cutts, David Gonzalez, Mary O'Brien, Jaishree Bhosle, Nicholas C. Turner, Sanjay Popat, Julian Downward
Journal: Journal of Clinical Oncology (2016)

e23027 Background: EGFR circulating tumour DNA (ctDNA) is a dynamic blood-borne marker predictive of EGFR tyrosine kinase inhibitor treatment response and disease progression. Microdroplet digital PCR (ddPCR) can detect low frequency EGFR ctDNA mutations but some patients have undetectable ctDNA levels. 54% of EGFR exon 19 deletion TCGA lung adenocarcinoma patients are also EGFR-amplified. We hypothesised that patients with EGFR co-amplification would have more abundant EGFR ctDNA. Methods: We designed a novel single-well ddPCR multiplex assay assessing EGFR copy number against 3 reference genes, RNA5SP233, SPATA18 and RPPH1, and EGFR exon 19 deletion allele frequency. We combined an in-house TaqMan assay with a TaqMan Copy Number Reference Assay (Life Technologies), a PrimePCR ddPCR Copy Number Assay (Bio-Rad) and a previously published EGFR mutation assay using the Bio-Rad QX200 system. DNA was extracted from cell lines, FFPE tissue and plasma from patients with advanced EGFR exon 19 deletion mutant lung adenocarcinoma and analysed for both EGFR molecular aberrations. Results: EGFR copy number and mutant allele frequency was validated in cell lines across different tumour types and copy number states. On and off chromosome reference genes performed well as references for EGFR (SD EGFR copy number to reference 0.01-0.8). 4/12 FFPE samples were amplified and mutated. Matched plasma samples had no detectable EGFR ctDNA and were not EGFR-amplified, suggesting little ctDNA content. Patients with non-amplified FFPE samples had no ctDNA EGFR amplification, including on disease progression. Two patients with circulating EGFR T790M mutations were not EGFR-amplified. Conclusions: EGFR copy number can be serially assessed from patient-derived material with ddPCR. In this limited cohort, EGFR amplification is not an evolving mechanism of therapeutic resistance that is detectable in plasma. In patients with known EGFR amplification, absence of EGFR amplification and mutant ctDNA can indicate low ctDNA levels and suggests that sampling of larger blood volumes or alternative disease surveillance methods be used.
TCT-443 Quantitative assessment of aortic regurgitation in 7 different types of aortic valves after transcatheter aortic valve implantation: a multicenter analysis by an independent core lab not sponsored by the industry
Authors: Patrick Serruys, Rodrigo Modolo, Yosuke Miyazaki, Chun Chin Chang, Norihiro Kogame, Nicolo Piazza, Michele Pighi, Mohammad Abdelghani, Mohamed Abdel-Wahab, Zouhair Rahhab, Osama Soliman, Yoshinobu Onuma, Fabio Brito, Pedro A. Lemos, Nicolas Van Mieghem
Journal: Journal of the American College of Cardiology (2018)
A novel approach to mine the Veterans Administration Informatics and Computing Infrastructure (VINCI) allows one to assess the efficacy of cancer therapies: Abiraterone and enzalutamide in Veterans with metastatic prostate cancer (PC).
Authors: Harshraj Leuva, Keith Sigel, Julia Wilkerson, Yeun-Hee Anna Park, Glen McWillimas, Christopher B. Anderson, Ta-Chueh Hsu, Pasquale Rescigno, Johann S. De Bono, David Henry Aggen, Charles G. Drake, Erik Langhoff, Susan Elaine Bates, Antonio Tito Fojo
Journal: Journal of Clinical Oncology (2018)

6586 Background: Novel efficacy endpoints are needed that correlate with overall survival [OS] and can describe real world outcomes. Methods: We mined national VA data (VINCI) using a novel set of equations validated in > 10,000 patients that estimate simultaneously occurring exponential rates of tumor growth [g] and regression [d] using data gathered while a patient receives cancer treatment. We have previously established that g is highly correlated with OS and can esti mate doubling time (dt). Importantly, since the equations include time as a variable, this approach is ideal for real world analyses where re-assessments depend on the practitioner and are highly variable. To validate g in a real-world cohort, we collected cases of PC, demographics, treatments and outcomes from VINCI and compared parameters by receipt of chemotherapies for PC. Results: 5,890 Veterans were treated with abiraterone [ABI], enzalutamide [ENZA] or both. Median age was 75 years including 2,596 Veterans > 80 years, and 23% identified as African American [AA]. PSA values beyond the initial measurement were available in 88% of patients with little clinical difference between those with and those without serial PSA values. g and d could be estimated in 83-85%f Veterans with p-values for fits < 0.1 in all and < 0.001 in the majority. g values for Veterans receiving either ABI [0.0038d-1; dt 182d] or ENZA [0.0040d-1; dt 173d] in first line were indistinguishable (p = 0,27), suggesting comparable efficacy. Consistent with the clinical bias, in second line, ENZA [0.0071d-1; dt 98d] appears superior to ABI [0.0091d-1; dt 76d] (p < 0.01). However, preliminary analyses find g on 1st line ABI remains constant in the majority and ABI continuation may be beneficial. Importantly g was independent of age, treatment location, and race, demonstrating comparable benefit in AA and non-AA Veterans. Conclusions: This is the largest real world assessment of ABI and ENZA efficacy in PC with a high percentage of AAs. The results underscore the value of determining g as an excellent measure of efficacy and argue for its use in outcomes research.