tbuckley/cabot-search huggingface dataset:
Designing comprehensive patient and family centered oncology care to achieve value based quality outcomes: Lessons learned from the field in creating sustainable change.
Authors: Tamira Harris, Lalan S. Wilfong
Journal: Journal of Clinical Oncology (2017)

e18225 Background: Of all clinical specialties cancer care is often thought of as one of the most patient and family centered due to the nature of the disease and course of treatment. Traditionally a strong relationship is held among the physicians, office practice staff and patients and family. Cancer care requires multidisciplinary collaboration and alignment for the optimized patient experience. Comparatively speaking this has been the case. The office based oncology care team has worked side by side to move the patient through the system during various treatments and settings. Most often the relationships and bonds that are formed are long lasting as cancer is a life changing experience. Opportunities for change however do exist and are needed in today’s increasingly complex healthcare environment. As demographics shift, and treatment methodologies continue to be discovered costs have escalated giving rise to the need to evaluate different care delivery models such as value based care. The Centers for Medicaid and Medicare Innovation Center (CMMI) Oncology Care Model (OCM) initiative has addressed this in their 5 year OCM pilot. Methods: Using qualitative and six sigma lean techniques practices redesigned patient throughput and experience based on data from gap analysis assessments, observation and collaboration. Results: The session will highlight lessons learned from the practice setting in initiating the changes required to meet CMS objectives and change the face of oncology care. Learn how practices designed patient navigation, created care team huddles, designed technology that facilities decision making, identified new models and partnerships for care, and standardized approaches across practice sites among other successes. Conclusions: This interactive session will explore what worked well, what physicians would change, and next steps planned.
TAS-118 (S-1 plus leucovorin) versus S-1 in gemcitabine-refractory advanced pancreatic cancer: A randomized, open-label, phase III trial (GRAPE trial).
Authors: Makoto Ueno, Tatsuya Ioka, Hideki Ueno, Joon Oh Park, Heung-Moon Chang, Naoki Sasahira, Masashi Kanai, Ik-Joo Chung, Masafumi Ikeda, Shoji Nakamori, Nobumasa Mizuno, Yasushi Omuro, Taketo Yamaguchi, Hiroki Hara, Kazuya Sugimori, Junji Furuse, Masahiro Takeuchi, Takuji Okusaka, Narikazu Boku, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (2017)

4099 Background: Addition of oral leucovorin (LV) to S-1 significantly improved progression-free survival (PFS) in a previous randomized phase II trial in Japanese patients (pts) with gemcitabine (GEM)-refractory advanced pancreatic cancer (PC). TAS-118 is an oral drug containing S-1 and LV. This phase III trial conducted in Japan and Korea compared overall survival (OS) between GEM-refractory advanced PC pts treated with TAS-118 and S-1. Methods: GEM-refractory PC pts were randomized in a 1:1 ratio to receive TAS-118 (S-1; 40-60 mg and LV; 25 mg bid for 1w, q2w) or S-1 (S-1; 40-60 mg bid for 4w, q6w). The primary endpoint was OS. The secondary endpoints included PFS, overall response rate, disease control rate, duration of response, and safety. Results: Five hundred and eighty-six pts were eligible for efficacy assessment (TAS-118: n=296 and S-1: n=290). Baseline characteristics were well balanced between the treatment arms. TAS-118 did not result in a statistically significant improvement in OS compared with that achieved with S-1 (median OS, 7.6 months vs. 7.9 months; hazard ratio [HR], 0.98; 95% CI, 0.82 to 1.16; P=0.756). However, it significantly improved PFS compared to that achieved with S-1 (median PFS, 3.9 months vs. 2.8 months; HR, 0.80; 95% CI, 0.67 to 0.95; P=0.009). Pre-planned subgroup analysis of OS showed significant interactions between the treatment effects and pancreatic resection (P=0.025), and between the treatment effects and country (P=0.004). Grade 3/4 drug-related adverse events (≥5% incidences) in TAS-118 and S-1 arms included diarrhea (7.0% vs. 7.3%), anorexia (6.7% vs. 5.0%), stomatitis (6.7% vs. 0.7%), and anemia (3.3% vs. 5.0%). Conclusions: The primary endpoint was not met. Further, the interactions between the treatment effects and pancreatic resection, and between the treatment effects and country, might affect the results. Clinical trial information: 132172. [Table: see text]
MET exon 14 splice site mutation, protein expression, and amplification in pulmonary sarcomatoid carcinoma: A multi-center study from China.
Authors: Xinru Chen, Fang Wang, Chunwei Xu, Wen yong Sun, Fang san Gao, Yu Zhang, Wen xue Liu, Likun Chen
Journal: Journal of Clinical Oncology (2017)

e20595 Background: MET exon 14 splice site mutation (MET exon 14Δ) was identified as a potential driver mutation in non-small cell lung cancer (NSCLC). Previously, several small sample size studies have revealed a higher frequency in pulmonary sarcomatoid carcinoma (PSC) than other types of NSCLC. In order to reveal the accurate frequency of MET gene alterations in Chinese PSCs, we comprehensively studied the frequency and the relationship among MET exon 14Δ, protein expression and amplification in a large cohort of PSCs. Methods: MET exon 14Δ, protein expression and amplification were detected in 148 surgically resected PSC samples from multiple medical centers by using Sanger sequencing, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. Results: MET exon 14Δ was identified in 9 (6.1%) of 148 cases. Six were pleomorphic carcinoma, two were spindle cell carcinoma and one was carcinosarcoma. MET exon 14Δ was more common in pleomorphic carcinoma compared with other subtypes of PSCs (p = 0.01, X 2 test) and have an obvious tendency to occur in elder patients. MET protein overexpression was detected in 16.2% (24/148) of PSCs, and was found significantly associated with MET exon 14Δ (p = 0.045). MET FISH positive was detected in 15.5% (23/148), and 6 (4.1%) of them were confirmed as gene amplifications. MET FISH positivity (P &lt; 0.001, X 2 test) and amplification (P &lt; 0.001, X 2 test) were significantly associated with the IHC positive. No significant relationship between MET exon 14Δ and amplification was found. Conclusions: Chinese PSC has high incidence of METexon 14Δ and amplication. MET inhibition may benefit this specific subgroup of patients.
Modified FOLFOX6 with or without radiation in neoadjuvant treatment of locally advanced rectal cancer: Final results of the Chinese FOWARC multicenter randomized trial.
Authors: Yanhong Deng, Pan Chi, Ping Lan, Lei Wang, Weiqing Chen, Long Cui, Daoda Chen, Jie Cao, Hongbo Wei, Xiang Peng, Zonghai Huang, Guanfu Cai, Ren Zhao, Zhongcheng Huang, Yiding Luo, Hongfeng Zhou, Yisheng Wei, Hao Zhang, Jian Zheng, Jianping Wang
Journal: Journal of Clinical Oncology (2018)

3502 Background: The FOWARC trial compared FOLFOX6 with or without Radiation in neoadjuvant treatment of locally advanced rectal cancer to 5-FU chemoradiotherapy. First results of early secondary endpoints have been published (Deng et al., JCO 2016). Here we present the primary endpoint, disease-free survival (DFS) at 3 years. Methods: Between 01/2011-02/2015, patients with rectal cancer within 12 cm from the anal verge, clinical stage II-III were randomly assigned to received 5-FU with radiation(RT) (FU-RT arm), or receive mFOLFOX6 with RT (FOLFOX-RT arm), or receive 4-6 cycles of mFOLFOX6 alone (FOLFOX arm), peri-operative RT was allowed if needed. The primary endpoint was DFS at 3 years defined as the interval from randomization to incomplete surgical resection, locaregional or metastatic recurrence or death, whichever occurred first. Results: A total of 495 patients were randomly assigned to three arms at 1:1:1 ration. 418 patients who had available follow up and obeyed the treatment protocol, 130 in FU-RT arm, 142 in FOLFOX-RT arm and 146 in FOLFOX arm. The local recurrence rate was 10.0%, 8.5% and 8.9% respectively. After a median follow-up time of 45.2 months, 35 patients in FU-RT arm had a DFS-related event, as compared with 37 patients in FOLFOX-RT arm(HR 1.031, 95% confidence interval 0.657 to 1.620), and 41 in FOLFOX arm (HR 0.960, 95% confidence interval 0.615 to 1.497). The rate of DFS at three years was 76.4±3.8% in FU-RT arm, 77.8±3.5% in FOLFOX-RT arm and 75.7±3.6% in FOLFOX arm (P = 0.961 by the exact stratified log-rank test). The rate of OS at three years was 93.7±2.2% in FU-RT arm, 92.0±2.3% in FOLFOX-RT arm and 92.2±2.3% in FOLFOX arm (P = 0.961 by the exact stratified log-rank test). Conclusions: FOLFOX with or without radiation did not improve significantly improved DFS in patients with advanced rectal cancer. However, FOLFOX alone seems to have identical local recurrence rate and 3-DFS and 3-OS compared to standard FU-RT. Clinical trial information: NCT01211210.
TCT-172 Aortic Valvar Complex and Cardiac Anatomy: Gender-Related Differences in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Samantha Vidal, Mathew Williams, Hanah Lee, Cezar Staniloae, Eleonora Vapheas, Zhen-Gang Zhao, Run Du, Moyang Wang, Muhamed Saric, Peter Neuburger, Michael Querijero, Alan Vainrib, Kazuhiro Hisamoto, Nicholas Amoroso, Tara Collins, Emily Clark, Illya Pushkar, Tonya Robin, Danielle Sin, Zachary Taylor, Binita Shah, Daniel Bamira, Ricardo Benenstein, Hasan Jilaihawi
Journal: Journal of the American College of Cardiology (2018)
The predicted potential of quantitative t cell repertoire analysis using next-generation sequencing in anti-PD-L1 treatment in NSCLC patients.
Authors: Qiong Zhao, Huaibo Sun, Yuqi Wang, Ning Li, Mingjiao Sun, Yina Wang, Yanfang Guan, Xuefeng Xia, Ling Yang, Xin Yi
Journal: Journal of Clinical Oncology (2018)

e24220 Background: Atezolizumab was the first PD-L1 inhibitor approved by the US Food and Drug Administration (FDA) for patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. However, the objective response rates (ORR) of this drug was only 22 %, approaches must be developed to identify which patients are likely to achieve benefit. Hence, we evaluated the potential efficacy of quantitative T cell repertoire in peripheral blood mononuclear cells (PBMC) in patients treated with atezolizumab. Methods: We identified a total of 10 mNSCLC patients received atezolizumab intravenously every 3 weeks(Q3W) with a dosage of 1,200 milligrams (mg) until disease progression. Tumor response was evaluated after two drug cycles(Q6W) according to the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (Version 1.1).The quantitative T cell repertoire of T cell receptor chains were analyzed using next generation sequencing before and after the first dosage, and four patients went through multi-period sampling before each cycle. Results: Totally, six patients achieved stable disease (SD), while four had disease progression (PD). The shared clones of PBMC before and after the first dosage were evaluated, and the SD patients possessed more shared clones than the PD patients (p= 0.038). Among the multi-period sampling patients, a trend of a higher shared clones in SD patients was observed at each dosage cycle . Conclusions: These results show that the noninvasive assessment of T cell repertoire may be a potential predictor to evaluate the response of patients treated with anti-PD-L1 antibody like atezolizumab. However, considering the limited number in this study, a larger number of patients are being included subsequently.
CDKN2A deletion as a prognostic marker: A clinico-genomic analysis of sarcoma patients.
Authors: Nam Bui, Joanna Przybyl, Lynn Million, Matt Van De Rijn, Kristen N. Ganjoo
Journal: Journal of Clinical Oncology (2018)

11543 Background: Sarcomas are a heterogeneous group of tumors with variable tendencies for aggressive behavior. Molecular markers for prognosis are needed to help risk stratify patients and potentially identify those who may benefit from more intensive therapeutic strategies. Methods: We analyzed somatic tumor genomic profiles in 152 soft tissue (STS) and bone sarcoma (BS) patients as part of 1,282 oncologic patients sequenced at Stanford Cancer Institute. We also examined 206 STS patients with whole exome and RNAseq from The Cancer Genome Atlas (TCGA). Results: Compared to all other histologies, sarcomas were found to be driven by copy number and fusion alterations with the highest relative percentage of amplifications/deletions/fusions (BS 53%, STS 57%, lung cancer 34%, melanoma 26%) and the lowest average SNV count (BS 1.7, STS 1.8, lung cancer 3.4, melanoma 6.1) The most common genomic alterations were TP53 mutation (34%), CDKN2A deletion (21%), RB1 deletion (11%), TP53 deletion (8%), MDM2 amplification (8%), and PIK3CA mutation (6%). When all genomic alterations were tested for prognostic significance in the cohort of localized STS (n = 96), only CDKN2A alterations (n = 22) correlated significantly with prognosis with a hazard ratio (HR) of 2.83 for overall survival (p = 0.01). There was a trend towards earlier recurrence for CDKN2A patients (p = 0.08) and no difference in chemotherapy time to treatment failure (p = 0.26), suggesting that CDKN2A alterations portend a more aggressive course but not necessarily any additional chemo resistance. These findings were validated in the TCGA dataset where CDKN2A altered patients (n = 24) had significantly worse overall survival with a HR of 2.55 (p = 0.004). Gene Ontology enrichment analysis revealed upregulation of pathways involved in RNA processing, protein translation, and catabolic processes. Conclusions: This is the first study to suggest that CDKN2A deletion is a poor prognostic marker in STS. Further research is warranted towards novel agents that affect the CDKN2A pathway and whether aggressive adjuvant therapy can attentuate the poor prognosis. We are undertaking further study towards the correlation of loss of p16 expression as an IHC biomarker for CDKN2A deletion.
Combined HDAC and BET inhibition to enhance cancer vaccine-elicited T-cell responses.
Authors: Alexander Badamchi-Zadeh, Kelly Dare Moynihan, Nicholas M Provine, Rafael Larocca, Darrell J Irvine, Dan H Barouch
Journal: Journal of Clinical Oncology (2017)

e14632 Background: The combined inhibition of histone deacetylases (HDAC) and the proteins of the bromo and extra terminal (BET) family have recently shown therapeutic efficacy against pancreatic ductal adenocarcinoma, melanoma and lymphoma cancers in murine studies. However, in these studies the role of the immune system in therapeutically controlling these cancers was not explored. Methods: We sought to investigate the effect of the HDAC inhibitor romidepsin (RMD) and the BET inhibitor I-BET151, both singly and in combination, on vaccine elicited immune responses. C57Bl/6 mice were immunized with differing vaccines (Adenoviral, protein) in prime-boost regimens, under treatment with RMD, I-BET151, or RMD+I-BET151. Results: The combination RMD+I-BET151, administered during Adenoviral prime-boost vaccination, resulted in the significant increase in the frequency and number of antigen-specific CD8 T cells. RMD+I-BET151 treatment affected vaccine-elicited secondary T cell responses, significantly increasing the frequency of IFN-γ+ splenic CD8 T cells and maintaining their dual IFN-γ+TNFa+ polyfunctionality. These CD8 T cells maintained their protective ability against Listeria monocytogenes, and protected against B16-OVA challenge. The significant augmentation of vaccine elicited CD8 T cell responses under RMD+I-BET151 treatment was additionally observed following protein (OVA+CpG) prime-boost vaccination, resulting in greater protection against B16-OVA challenge and enhanced survival. T-regulatory cell (FoxP3+CD4+) frequency and total CD4 and CD8 cell numbers remained unaltered following RMD+I-BET151 treatment. Conclusions: Combined HDAC and BET inhibition resulted in greater vaccine-elicited CD8 T cell responses following immunization by multiple vaccine platforms, and enhanced protection against B16-OVA challenges. We are currently assessing immunological mechanisms of action for this combined HDAC and BET inhibition.
The benefit of cost-sharing subsidies in the treatment of chronic myeloid leukemia (CML) after price surging of tyrosine kinase inhibitors (TKIs).
Authors: Erlene Kuizon Seymour, Julie George, Julie J. Ruterbusch, Jennifer Lynn Beebe-Dimmer, Charles Alan Schiffer
Journal: Journal of Clinical Oncology (2018)

e18889 Background: Prior studies have shown that subsidies for low-income patients (LIS pts) improve TKI initiation. Prices increased after 2010 when more TKIs for frontline treatment were approved. We compared TKI use and cost before and after 2010 among Medicare pts with Part D pharmacy benefits. Methods: Using the SEER-Medicare database, we identified CML pts from 2007-2013 with continuous Part D coverage. TKI initiation = claim within 6 months of diagnosis. TKI adherence = > 80% prescription days within 6 months of initiation. Logistic regression was used to estimate the odds of TKI initiation/adherence adjusted for age, gender, race, marital and subsidy status. Total Medicare D cost and pt cost-sharing (copay + coinsurance) were based on the 1st month supply. Results: 661 pts were included. Median Medicare cost nearly doubled, although cost-sharing remained the same or slightly lower. Most TKI users reached catastrophic coverage (pt cost > $4550-4750) within 6 months, which increased over time (81% to 86%). LIS pts were significantly more non-White, female, and single. TKI initiation rates significantly increased over the time periods, especially in LIS pts. TKI adherence increased modestly with no difference based on subsidy status. Pts > 80 yrs also had decreased initiation and adherence. Costs for the 1st month and TKI use Conclusions: Despite increased prices after 2010, cost-sharing subsidies are associated with improved TKI initiation rates among LIS pts. Interventions to decrease cost-sharing of pts above poverty level are needed. 2007-2010 N = 318 2011-2013 N = 343 First TKI Imatinib (94%) Imatinib (55%) Dasatinib (27%) Nilotinib (18%) COSTS Median (range) Median (range) Total Medicare Costs $4175 (930-14223) $7245 (1727-13885) Patient Cost-Sharing All $1395 (0-5230) $890 (0-3618) With LIS (n = 182) $4 (0-3725) $4 (0-2746) Without LIS (n = 450) $2309 (6-5230) $2221 (0-3618) TKI USE Rate Rate OR (95% CI) TKI Initiation All 62.9% 74.9% 1.70 (1.19, 2.41) With LIS 61.5% 86.1% *3.59 (1.68, 7.71) Without LIS 62.4% 71.8% *1.44 (0.96, 2.18) TKI Adherence All 73.5% 79.5% 1.37 (0.88, 2.15) With LIS 74.6% 81.7% - Without LIS 74.2% 78.3% - *Difference between +/- LIS over time periods
P22 ASTRIS a RWT with Osimertinib in NSCLC EGFR T790M Mutated: Disease Characteristics from Patients Included in Argentina
Authors: M. Biolchi, G. Recondo, M. Casalnuovo, F. Tsou, I. Diaz Perez, F. Reinhold, C. Martín
Journal: Journal of Thoracic Oncology (2018)
EGFR protein expression of the metastatic colorectal cancer as a prognostic/predictive factor for anti-EGFR antibody therapy.
Authors: Jozsef Timar, Violetta Piurko, Istvan Kenessey, Erzsebet Raso, Erika Lahm, Edina Kiss, MArta Sikter, Jozsef Vachaja, Zsuzsa Papai, Andrea Uhlyarik
Journal: Journal of Clinical Oncology (2018)

e15548 Background: Anti-EGFR monoclonal antibody therapy is a standard treatment of advanced colorectal cancer. Unlike in case of other target therapies the target of anti-EGFR monoclonal antibodies, EGFR protein itself was proved to be an unreliable positive predictor. Here we have attempted to analyse the predictive role of EGFR protein expression in a KRAS exon2 wild-type metastatic colorectal cancer cohort treated with anti-EGFR therapies where survival data have been available. Methods: 97 primary colorectal carcinoma and 33 corresponding metastatic FFPE tissue was used in this study. EGFR protein expression of colorectal cancer tissue was determined by immunohistochemistry on Benchmark Ultra automatic stainer (Ventana, Tucson, Ar). EGFR protein was detected using ready-to-use mouse monoclonal anti-EGFR antibody 3C6 (Confirm anti-EGFR antibody, Ventana). Membranous EGFR protein expression level of the primary tumors (n = 97) and available metastases (n = 33) was determined by light microscopy using the industrial standard H-score semiquantitative methodology by combining the % of positive cells and the 3-level intensity ranges and defined as 0-300. This study was approved by the local IRB (IKEB19/1043) Results: Our data indicate that in case of the primary tumors lower than chosen threshold EGFR-protein expression was associated with longer progression-free- (PFS) or overall survival (OS), however the difference was statistically significant in OS at 200 threshold exclusively (p < 0.05). In case of the metastatic tissues, data indicated that lower-than threshold EGFR protein levels were associated with significantly (p < 0.05) longer PFS at H-score = 0 and OS at H-scores = 0, = 50 and = 100 and the differences were the largest at 0-threshold. Conclusions: According to these observations, the possible negative predictive role of the EGFR protein expression in RAS-wild-type colorectal cancer metastases must be vigorously tested in larger data-sets of anti-EGFR antibody treated colorectal cancers due to possible clinical impact. Grant support: NKFI-K-116151
Effects of temozolomide and bevacizumab in relapsed patients with heavily pretreated uterine leiomyosarcoma.
Authors: Hiroko Matsuura, Sayaka Ikeda, Kazuya Kudoh, Naoki Sasaki, Masashi Takano, Tomoko Goto, Ryoko Kikuchi, Tsunekazu Kita, Masaru Sakamoto, Daisuke Aoki, Nobuyuki Susumu, Hiroko Kouta, Yoshihiro Kikuchi
Journal: Journal of Clinical Oncology (2017)

11056 Background: Uterine leiomyosarcomas (ULMs) tend to recur regardless of their stage, and there is no satisfactory report for relapsed ULMs. Temozolomide (T) is derivatives of dacarbazin and these agents have been used for treatment of ULMs. ULMs has a plenty of vessels compared to uterine myoma so that bevacizumab (B) was used in ULMs. In the present study, we evaluated the effect of TB in heavily pretreated relapsed ULMs. Methods: From 2009 to 2016, total 19 patients (pts) with heavily pretreated ULMs were enrolled. Patients were treated with T (80mg/body/day) and B (2mg/kg; days 1, 8 and 15, q4 weeks). Treatment was continued until disease progression and/or unmanageable toxicities. Response was evaluated with the response evaluation criteria in solid tumors (RECIST) v1.1, and adverse effect (AE) was assessed by common terminology criteria for adverse events (CTCAE) v4.0. Results: Seventeen of 19 pts were subjected to response evaluation. Median age of pts was 56.3 years (range: 31-69). Three pts (18%) had complete response (CR), 2 (12%) had partial response, and 7 (41%) had stable disease (SD). The response rate (RR: CR+PR) and clinical benefit rate (CBR: CR+PR+SD) were 29% and 71%. The median progression-free survival was 14.2 months (range: 0-89). Median administration cycle was 9.5 (range: 2-48). AE with grade 3 and more over were observed in 6 pts. There was one dead case from perforation, but toxicity was almost manageable. Conclusions: We experienced 3 cases of CR, and two of them had CR for more than two years. Intriguingly, TB could be substantially effective even in relapsed patients with heavily pretreated ULMs. These results warrant further prospective and randomized studies.