tbuckley/cabot-search huggingface dataset:
Piloting a generic cancer consumer quality index for cancer patients in European countries.
Authors: Anke Wind, Jana Heerink, Herman Sixma, Pietro Presti, Claudio Lombardo, Wim H van Harten
Journal: Journal of Clinical Oncology (2016)

e18163 Background: Across health care systems, patient satisfaction has become an increasing concern over the past decades. Based on the Consumer Quality Index method(founded on Consumer Assessment of Healthcare Providers and Systems) a questionnaire was recently developed for Dutch cancer patients. As a next step, this study aimed to adapt and pilot this questionnaire for international comparison of cancer patients experience and satisfaction with care in 6 European countries; the European Cancer Consumer Quality Index (ECCQI). Methods: Firstly an already existing CQI for cancer patients was adapted for international use. A minimum of 100 patients per site were surveyed through convenience sampling. The CQI was translated into the local language at the participating pilot sites using cross-translation. Data from 7 pilot sites in 6 countries was collected through an online and paper based survey and analyzed with SPSS. Reliability was tested by calculating Cronbach’s alpha and validity by means of cognitive interviews. To measure whether the level of patient activation was a confounding factor, the Patient Activation Measure (PAM) was used. In order to examine to what extent the results of the ECCQI pilot are influenced by national cultural an explorative study using Hofstede’s cultural dimensions theory was applied. Demographic factors were compared as possible con-founders. Results: A total of 685 patients from six European countries filled the questionnaire. Cronbach’s alpha was good or satisfactory in 8 out of 10 categories. Patient satisfaction was scored very similar between the countries (3.27 – 3.46 on a scale from 1 to 4). Age, gender and level of activation were factors that had an influence on the outcomes as well as cultural differences. The results of the PAM show that respondents with a high level of activation have a tendency to score higher. Conclusions: This European Cancer Consumer Quality Index showed promising scores on reliability and a good internal validity. The ECCQI is up to our knowledge the first to measure and compare experiences and satisfaction of cancer patients on an international level. This ECCQI may enable healthcare providers to improve the quality of cancer care.
Assessment of activating estrogen receptor 1 (<i>ESR1</i>) mutations in gynecologic malignancies.
Authors: Stephanie Gaillard, Laurie M. Gay, Meghan Steiner, Kaitlyn Andreano, Brittany Anne Davidson, Laura Jean Havrilesky, Angeles Alvarez Secord, Fidel A. Valea, Gerardo Colon-Otero, Deborah A. Zajchowski, Ching-Yi Chang, Donald P. McDonnell, Andrew Berchuck, Julia Andrea Elvin
Journal: Journal of Clinical Oncology (2018)

5590 Background: Endocrine therapy is often considered to treat hormone-responsive gynecologic (gyn) malignancies. Mutations in ESR1 leading to constitutive transcriptional activity have been reported in estrogen receptor positive (ER+) breast cancers and may contribute to acquired resistance to endocrine therapy. Using comprehensive genomic profiling (CGP) we assessed the frequency of ESR1 activating genomic alterations (GA) in gyn malignancies. Methods: DNA from FFPE tumor tissue obtained during routine clinical care for 9645 gyn malignancies (ovary, fallopian tube, uterus, cervix, vagina, vulvar, and placenta) was analyzed for all classes of GA [base substitutions (muts), indels, rearrangements, and amplifications] in ESR1 by hybrid capture, next generation sequencing. Results: 295 ESR1 GA were identified in 285 (3.0%) cases; 10 cases contained 2 ESR1 GA each. wtESR1 amplifications were identified in 80 (0.8%) cases and mutESR1 were present in 86 (0.9%) cases. mutESR1 were more common in uterine compared to other cancers (2.0% vs < 1%, p < 0.001). mutESR1 were also enriched in carcinomas with endometrioid histology: 4.2% in uterine endometrioid vs 0.2% in uterine serous carcinomas (p < 0.001) and 3.5% in ovarian endometrioid compared to 0.3% in ovarian serous carcinomas (p < 0.001). The Y537S, D538G, L536P, and S463P mut comprised 35%, 17%, 13%, and 12%, respectively, of all mutESR1. Clinical data for multiple gyn malignancy patients demonstrate that mutESR1 may be a de novo or acquired endocrine resistance mechanism. Low-grade serous ovarian cancer (LGSOC) samples obtained at diagnosis and after recurrence in a patient treated with letrozole demonstrated an acquired mutESR1 Y537S. Another LGSOC patient had a mutESR1 Y537N at diagnosis and has attained prolonged clinical benefit ( > 4 years) with fulvestrant. Conclusions: ESR1 GA are present at a low frequency in gyn malignancies, are enriched in endometrioid histologic subtypes, and may occur either de novo or as a resistance mechanism to prior endocrine therapy. CGP identified clinically relevant ESR1 GA that may be useful in directing therapy of gyn malignancies.
Preclinical development of tumor-infiltrating lymphocyte (TIL) based adoptive cell transfer (ACT) immunotherapy for patients with sarcoma and the potential benefit of anti-CD137 stimulation.
Authors: Morten Nielsen, Anders Krarup-Hansen, Dorrit Hovgaard, Michael Mørk Petersen, Anand Chainsukh Loya, Marie Christine Wulff Westergaard, Inge Marie Svane, Niels Junker
Journal: Journal of Clinical Oncology (2017)

e14545 Background: Tumor specific TILs can be in vitro expanded and have the ability to induce complete and durable tumor regression in some patients following ACT. In this preclinical study we investigated the feasibility of expanding TILs from sarcomas, as well as performing functional in vitro analyses on these. Methods: Fresh tumor samples from sarcoma patients were obtained, and TILs were isolated and expanded in growth medium containing IL-2. In a sub study, we investigated the effect of adding an agonistic CD137 antibody (Urelumab, BMS) and/or an anti-CD3 antibody (OKT3) to the medium. Phenotype and functional analyses was performed using flow cytometry and IFNγ-Elispot. Results: Tumor samples from 30 patients with various types of sarcomas were obtained, and we were able to expand a minimum of 40 million TILs from 27 of these. Mean expansion times were 32 days (14 - 61). 87,7 % (36,4 – 99,1) of these cells were CD3+, and of these, 66,7 % (16,3 – 99,1) were CD4+, and 21,8 % (0,1 – 50,6) were CD8+. A sub study revealed that adding anti-CD137 and/or OKT3 increased total yield of TILs; anti-CD137 skewed the phenotype significantly towards more CD8+ TILs and in some cases NK cells and γδ T cells. TILs from 8 of 17 tested tumor samples from four different sarcoma subtypes (undifferentiated pleomorphic sarcoma, myxofibrosarcoma, myxoid liposarcoma and osteosarcoma) demonstrated reactivity against autologous tumor cells using IFNγ-Elispot (40 – 500 spots per 100.000 TILs). In TILs stimulated with anti-CD137 the reactivity increased. Conclusions: We were able to expand TILs from 90 % of the acquired tumor samples to numbers needed for possible future clinical ACT implementation. Expanded TILs were a mix of CD4+ and CD8+ with CD4+ being predominant. Approximately half of the TIL cultures showed some degree of in vitro tumor reactivity as determined by Elispot. Early analyses suggest that addition of anti-CD137 could influence expansion time, phenotype, and functional capacity of the expanded TILs. Based on these results, we conclude that it is feasible to translate TIL based ACT into clinical testing in sarcoma patients.
Baseline characteristics as predictors of adjuvant chemotherapy (AC) toxicities in stage III colorectal cancer (CRC) patients.
Authors: Akie Watanabe, Charlie Yang, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2017)

e18237 Background: Toxicities acquired from AC can impact quality of life. Baseline patient characteristics such as age, sex, ECOG, tumor location, TNM staging, and comorbidities are frequently considered in AC treatment decision-making, but their associations with common toxicity outcomes remain unclear. Methods: We used a population-based cohort of CRC patients to test our hypothesis. We reviewed individuals treated with adjuvant monotherapy (Capecitabine) or combination therapy (FOLFOX or CAPOX) within 12 weeks of curative resection at any 1 of 6 cancer centers in British Columbia, and determined the associations between baseline characteristics and toxicity outcomes. Results: Among 371 patients, median age was 65 (range 26-86) years, 51.5% were men, and 14% were ECOG ≥2. In this cohort, 41% received monotherapy and 59% received combination therapy. For monotherapy, univariate analyses found that age, sex, ECOG, and pre-treatment anemia were associated with hematological toxicities ( P &lt; 0.05). Likewise, tumor location and TNM staging were associated with gastrointestinal (GI) toxicities ( P &lt; 0.05). On multivariate analyses, hematological toxicities were more likely to develop with old age (≥70) (OR 3.30, 95% CI 1.17-9.37, P= 0.025) and pre-treatment anemia (OR 23.18, 95% CI 6.36-84.48, P= 0.001), while GI toxicities were less likely to occur with a left-sided tumor (OR 0.38, 95% CI 0.15-0.99, P= 0.047). In univariate analyses of combination therapy, sex and pre-treatment anemia were also associated with hematological toxicities, while cardiac and/or respiratory comorbidities were associated with neuropathy ( P &lt; 0.05). In multivariate analyses, however, only female sex was predictive of hematological toxicities (OR 5.13, 95% CI 2.08-12.68, P= 0.001) and neuropathy was less likely to develop with cardiac and/or respiratory comorbidities (OR 0.23, 95% CI 0.07-0.81, P= 0.023). Further analyses did not show any consistent correlations between other baseline characteristics and toxicity outcomes. Conclusions: Readily available baseline patients characteristics are associated with the development of specific side effects, which can be used to better inform AC discussions.
VEGFR2 cytoplasmic expression (VEGFR2ce) in relation to survival in metastatic breast cancer (MBC) patients (pts) treated with bevacizumab (Bev).
Authors: Roseana Melo Borba, Tiago Cordeiro Felismino, Alexandre Andre B. A. Da Costa, Vladmir C. Lima, Marcelo Corassa, Stephania Bezerra, Cynthia Bueno de Toledo Osorio, Tadeu Ferreira Paiva
Journal: Journal of Clinical Oncology (2017)

11523 Background: Bev is a monoclonal antibody that binds to VEGFA that demonstrated improved progression free survival (PFS) in MBC clinical trials. VEGFR2, NOTCH1, Integrin a1b2 and ILK are angiogenesis-related proteins possibly related with Bev efficacy. The correlation of these proteins expression and Bev survival variables was evaluated. Methods: We retrospectively analyzed 1 st line chemotherapy in two HER2 negative MBC cohorts. Pts were treated between May-07 and July-14. Cohort 1 (C1) was treated with paclitaxel and Cohort 2 (C2) with paclitaxel and Bev. Expression of biomarkers was determined by immunohistochemistry. Tumor samples were arranged on a tissue microarray. Survival curves were calculated by Kaplan-Meier method and log-rank test. Cox model was used in multivariate analysis. Results: C1 had 42 pts. Median age was 63y. Tumor subtypes were divided in luminal (92.9%) and triple negative (TN) (7.1%). Visceral metastasis (mets) were present in 71.4%. Median follow-up (mFUP) time was 32.1m. mPFS was 8.0m and mOS was 33.5m. C2 had 29 pts. Median age was 57y. Luminal 79.3%; TN 20.7%; Visceral mets 79.3%; mFUP 38m. mPFS was 10.5m and mOS was 47m. In C2, high VEGFR2ce was correlated with improved PFS (high VEGFR2 16.5m x low VEGFR2 6.8m, p = 0.025). Breast cancer subtype, metastasis pattern and VEGFR2 expression were included in the multivariate analysis for PFS. VEGFR2 remained as independent factor (HR 0.35; IC95% 0.14 – 0.85, p = 0.021). In C1, VEGFR2 was not correlated with improved PFS (high VEGFR2 8.6m x low VEGFR2 8.0m, p = 0.24). Other markers were not associated with PFS. Conclusions: High VEGFR2ce was associated with increased PFS in patients treated with Bev. In MBC VEGFR2 may have a role as a predictive tool on benefit of antiangiogenic therapy.
Association of base excision repair gene polymorphisms with response to chemotherapy of advanced non small-cell lung cancer in a Chinese population.
Authors: Jie Dong, Xu Wang, Jiu Wei Cui
Journal: Journal of Clinical Oncology (2018)

e20504 Background: There are significantly differences in the efficacy of platinum based chemotherapy in NSCLC patients. Platinum leads to the cell death by damaging DNA through the chain cross link or chain cross-linking of DNA.Base excision repair (BER) plays an important role in the maintenance of genome integrity and anti-cancer drug resistance. There are a few researches on whether BER can influence the sensitivity of platinum-based chemotherapy, while the sample size is small and the influencing factors are poorly controlled, which needs further verifying. We eager to explore the role of BER genes polymorphisms in response to chemotherapy of advanced non small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Methods: During the period from November 2009 to January 2016, a total of 152 patients diagnosed with IIIB or IV stage NSCLC in the First Hospital of Jilin University were admitted into our study who were treated with platinum-based chemotherapy. The XRCC1 G28152A, MUTYH G972C, HOGG1 C1245G, PARP1 T2444C polymorphisms of all the patients were detected by the mass spectrometry. And use the Logistic regression to analysis the relationship between the BER genes polymorphisms and the curative effect of platinum-based chemotherapy. Results: The effective rates of chemotherapy in patients with PARP1 2444 TT, CC and TC genotype were 9/44 (20.5%), 15/28 (53.6%) and 28/76 (36.8%) respectively. Logistic regression model showed that the effective rate of chemotherapy of the PARP1 T2444C polymorphisms, CC genotype (OR: 5.216, 95%CI: 1.568-17.352, P= 0.007) and TC genotype (OR: 2.692, 95%CI: 1.007-7.198, P= 0.048) are significantly higher than the TT wild type, as well as the genotype of TC together with CC (OR: 3.178, 95%CI:1.229-8.219, P = 0.017). There is no relationship between G28152A, MUTYH G972C, XRCC1 HOGG1 C1245G gene polymorphism and chemosensitivity. Conclusions: PARP1 2444 mutation allele C might be associated with the decreased sensitivity to platinum based chemotherapy in advanced NSCLC. Our findings may be helpful towards designing individualized cancer treatment.
Cereblon modulator iberdomide induces degradation of the transcription factors Ikaros and Aiolos: immunomodulation in healthy volunteers and relevance to systemic lupus erythematosus
Authors: Peter H Schafer, Ying Ye, Lei Wu, Jolanta Kosek, Garth Ringheim, Zhihong Yang, Liangang Liu, Michael Thomas, Maria Palmisano, Rajesh Chopra
Journal: Annals of the Rheumatic Diseases (2018)

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Risk factors for conversion to snare resection during colorectal endoscopic submucosal dissection in an expert Western center
Authors: Enrique Pérez-Cuadrado-Robles, Christophe Snauwaert, Tom Moreels, Anne Jouret-Mourin, Pierre Deprez, Hubert Piessevaux
Journal: Endoscopy (2018)

Abstract Background There are limited data regarding the risk factors and consequences of conversion to endoscopic mucosal resection (rescue EMR) during colorectal endoscopic submucosal dissection (ESD) in Western centers. Methods This was a retrospective analysis of a prospectively collected database, from which 225 consecutive ESDs performed between 2013 and 2017 were selected. Of the included patients, 39 (18.6 %) required rescue EMR. Pre- and per-procedure characteristics were evaluated to determine the features associated with the need for rescue EMR. Outcomes and complications were also assessed. Results 210 patients were included, with median tumor size of 40 mm (range 20 – 110) and most tumors being in a non-rectal location (66.2 %). When compared with full ESD, rescue EMR was significantly associated with lower rates of en bloc resection (43.6 % vs. 100 %) and complete resection (R0 status; 28.2 % vs. 88.9 %), and with a higher rate of recurrence (5.1 % vs. 0 %) and more need for surgery (15.4 % vs. 3.5 %). In multivariable analysis, non-lifting (adjusted odds ratio [ORa] 3.06, 95 % confidence interval [CI] 1.23 – 7.66; P = 0.02), nongranular-type laterally spreading tumor (LST-NG; ORa 2.56, 95 %CI 1.10 – 5.99; P = 0.03), and difficult retroflexion (OR 3.22, 95 %CI 1.01 – 10.28; P = 0.049) were independent risk factors associated with conversion to rescue EMR, while tumor size and location were not. Conclusions During ESD, the presence of poor lifting, LST-NG morphology, and a difficult retroflexed approach were factors associated with the need to convert to rescue EMR. Conversion to rescue EMR remains a valuable strategy.
Comparison of somatic mutations profiles from next-generation sequencing (NGS) of cell-free DNA (cfDNA) versus bone marrow (BM) in acute myeloid leukemia (AML).
Authors: Rita Elias Assi, Maher Albitar, Wanlong Ma, Keyur Patel, Koichi Takahashi, Musa Yilmaz, Nicholas James Short, Elias Jabbour, Guillermo Garcia-Manero, Hagop M. Kantarjian, Zeev Estrov, Farhad Ravandi
Journal: Journal of Clinical Oncology (2018)

7051 Background: NGS of cfDNA is a novel non-invasive strategy to define mutational profiles in many solid tumors, and can be used for real-time molecular monitoring of treatment and detection of resistance or disease recurrence. We examined the feasibility of cfDNA NGS in AML and compared mutation profiles to a BM NGS panel at multiple time points during therapy. Methods: Plasma cfDNA was collected and analyzed using a capture-based NGS assay (Qia275) targeting 275 genes. BM NGS was performed on DNA extracted from the sample in CLIA-certified molecular diagnostics laboratory for the detection of somatic mutations in the coding sequence of 28 or 81 genes. NGS profiles from cfDNA and BM were analyzed with an established bioinformatics pipeline to identify somatic variants. Results: 24 patients (pts) with median age of 42 years (24-61) were prospectively enrolled and 13 had serial cfDNA and BM samples for testing. NGS analysis of cfDNA detected a median of 3 deleterious somatic mutations (range 1-22) (allele frequency (AF) > 0.1%, passing bioinformatic quality filters) with AF ranging from 1.5-96.5%. When matched to common mutations in both NGS panels, cfDNA harbored a median of 3 new mutations (1-8) in 83% (20/24) of pts, not detected in BM NGS panel. BM and cfDNA NGS detected identical mutations in 1/24 (4%) pt while BM NGS detected additional mutations in 3/24 (13%) pts where NGS cfDNA failed to do. Of the 20 pts on whom complete remission samples are available, 17 (85%) had a median of 3 alterations (2-8) by cfDNA including actionable mutations not detected by BM NGS. Conclusions: NGS of cfDNA is feasible in AML and successfully detects prior and novel mutations when BM sequencing shows absence of these mutations in a matched panel of genes. The discrepancies between BM and cfDNA mutation profiles seen in many pts may reflect leukemic evolution or intra-leukemic heterogeneity. Plasma cfDNA for genomic profiling is a promising and non-invasive strategy and further investigation of its utility is warranted in AML.
Correlation of CD8 lymphocytes in tumors and nonsynonymous mutational load with prognosis of bladder cancer patients treated with immune checkpoint inhibitors.
Authors: Boya Deng, Jae-Hyun Park, Lili Ren, Poh Yin Yew, Kazuma Kiyotani, Tatjana Antic, Kelly O’Connor, Peter H. O'Donnell, Yusuke Nakamura
Journal: Journal of Clinical Oncology (2018)

e16529 Background: Bladder cancer is the fourth most common cancer in males and the 11th most common in females, with a projected 81,190 new cases and 17,240 deaths in the USA in 2018.Anti-PD1 checkpoint inhibitors have recently demonstrated effectiveness against metastatic cancers including urothelial carcinoma.This study was designed to better understand the molecular mechanisms of response to immune checkpoint inhibitor therapy, Methods: In order to identify biomarkers/factors that correlate with the clinical response in advanced bladder cancer patients who received immune checkpoint inhibitor treatment, we investigated tumors from 18 bladder cancer patients who had received anti-PD1 (pembrolizumab) or anti-PD-L1 therapy (atezolizumab or durvalumab), and performed exome analysis, T-cell receptor (TCR) sequencing of the tumor-infiltrating lymphocytes (TILs) and immunohistochemical analysis of CD8 and PD-L1 in cancer tissues. Results: Immunohistochemical analysis of bladder cancer tissues demonstrated that a higher number of CD8 T cell infiltration into cancer tissues was significantly associated with longer cancer-specific survival of the patients (P = 0.0012). T cell receptor beta (TCRB) sequencing of TILs using genomic DNAs extracted from the tissues from 15 cases revealed that patients with higher clonal expansion of TILs had some tendency of longer cancer-specific survival (P = 0.055), compared with those with lower clonal expansion. We performed whole exome sequencing of 14 cases and found that patients carrying higher numbers of somatic mutations received greater benefit from immunotherapy (P = 0.034) and one patient who had high microsatellite instability has survived for 1034 days. Conclusions: CD8 infiltration in tumors and non-synonymous mutation load might be useful predictive markers for immune checkpoint inhibitors for bladder cancer patients.
Epacadostat plus nivolumab for advanced melanoma: Updated phase 2 results of the ECHO-204 study.
Authors: Adil Daud, Mansoor N. Saleh, James Hu, Jonathan Scott Bleeker, Matthew John Riese, Roland Meier, Li Zhou, Gul Serbest, Karl D. Lewis
Journal: Journal of Clinical Oncology (2018)

9511 Background: Indoleamine 2,3-dioxygenase 1 (IDO1) enzyme-induced immunosuppression in the tumor microenvironment supports tumor cell evasion of immune surveillance. Epacadostat (E) is a potent and selective oral inhibitor of the IDO1 enzyme. ECHO-204 is an open-label, phase (P) 1/2 study of E plus PD-1 inhibitor nivolumab (N) in patients (pts) with advanced cancer. Updated efficacy and safety/tolerability outcomes for the P2, advanced (unresectable or stage IV) melanoma cohort are reported. Methods: Pts received E (100 or 300 mg PO BID) plus N (240 mg IV Q2W). Response was assessed every 8 weeks (RECIST v1.1). Safety/tolerability was assessed in pts receiving ≥1 study treatment dose. PD-L1 expression was assessed (Dako 28-8 assay; PD-L1 positive: ≥1% tumor cell staining). Results: As of 29 Oct 2017, all of the planned 50 pts were enrolled in the P2 expansion cohort (n = 40 treatment naive for advanced disease). Median (range) duration of follow-up was 417 days (70 to 617 days). Across all pts, overall response rate (ORR) was 62% (31/50; 9 complete response [CR], 22 partial response [PR]) and disease control rate (DCR; CR + PR + stable disease) was 78% (39/50). In treatment-naive pts, ORR was 65% (26/40; 8 CR, 18 PR) and DCR was 80% (32/40); responses were observed in both PD-L1-positive pts (75% ORR [9/12]; 92% DCR [11/12]) and PD-L1-negative pts (56% ORR [9/16]; 69% DCR [11/16]); the majority (88%; 23/26) of responses were ongoing at data cutoff; duration of response ranged 55+ to 565+ days (median not reached); rate of progression-free survival at 6 and 12 months was 77% and 63%, respectively (median not reached); and the rate of overall survival at 12 months was 92% (median not reached). In the overall population (N = 50), the rate of grade ≥3 treatment-related adverse events (TRAEs) was 48% with E 300 mg BID (n = 42; most common grade ≥3 TRAEs: rash [19%], ALT increase [12%]) and 13% with E 100 mg BID (n = 8; pneumonitis [13%] was the only grade ≥3 TRAE). Eight pts discontinued treatment due to TRAEs (all E 300 mg BID). There was no AE-related death. Conclusions: E + N continues to show promising antitumor activity in pts with advanced melanoma and is generally well tolerated. E 100 mg BID is the selected dose for P3 studies of E + N in pts with advanced cancer. Clinical trial information: NCT02327078.