tbuckley/cabot-search huggingface dataset:
Genetic diversity of HPV in tissues of tumors of the reproductive organs in women.
Authors: Galina Andreevna Nerodo, Oleg Ivanovich Kit, Tatiana Zykova, Victoria A. Ivanova, Vera P. Nikitina, Ekaterina A. Nerodo, Olga A. Bogomolova, Ekaterina V. Verenikina, Oksana E. Kravtsova
Journal: Journal of Clinical Oncology (2017)

e17001 Background: The purpose of the study was to determine the rate of various HPV genotypes detection in tissues of tumors of the female reproductive organs. Methods: FFPE and frozen tissue samples of cervical cancer (n=126), vulvar cancer (n=113) and uterine cancer (n=29) were studied. DNAs of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 were determined by the Real-Time PCR. Results: HPV DNAs were found in 94.4% of samples of cervical cancer tissue, 65.5% - uterine cancer tissue and 28.3% - vulvar cancer tissue. HPV 16 and 18 were the most frequent (78.8%). HPV 16 in cervical cancer was detected in 60.9%, vulvar cancer – 59.0% and uterine cancer – 54.5%. On the contrary, HPV 18 was more frequent in uterine cancer (40.9%) and less frequent in cervical cancer (18.4%) and vulvar cancer (2.7%). Besides HPV 16 and 18, genotypes 31, 33, 35, 39, 45, 51, 52, 56 and 59 were found in tumor tissues as well (21.2% in total). HPV 35, 52 and 56 were the most frequently detected. Cervical cancer tissues showed the greatest genetic diversity of HPV and uterine cancer tissues – the lesser one (HPV 35 only, besides HPV 16 and 18). Combination of several HPV types was also more frequent in cervical cancer (37.0% of positive samples); in vulvar cancer – 18.8% and in uterine cancer – 15.8%. Conclusions: The results confirm HPV significance in carcinogenesis of cervical cancer, vulvar cancer and probably uterine cancer and show genetic diversity of HPV in different localizations of tumors of the female reproductive system.
Association between patient perception of oncology clinical trial participation and survival: N0392 (Alliance).
Authors: Jennifer Le-Rademacher, Amylou C. Dueck, Cynthia Chauhan, Daniel V. Satele, Jeff A. Sloan
Journal: Journal of Clinical Oncology (2016)

e18122 Background: We previously reported that patient subjective perception of their oncology clinical trial experience was influenced by factors beyond their treatment outcome (Chauhan, ASCO, 2012). This study assesses the association between patient perception of clinical trial participation and survival. Methods: This analysis included data from patients enrolled in 31 Phase I and II clinical trials conducted by the North Central Cancer Treatment Group (NCCTG) who completed the Was It Worth It (WIWI) satisfaction assessment one month after trial registration. A landmark analysis was conducted where only patients who were alive at the time of assessment were included in the analysis of overall survival (OS) and only those alive without progressive disease were included in the analysis of progression-free survival (PFS). The time to event for both outcomes starts at the time of assessment. OS and PFS probabilities were estimated using the Kaplan-Meier estimator. The log-rank test was used to compare OS and PFS between patients who were satisfied with their participation vs. those who were not. Results: Among 544 patients who were alive and completed the WIWI assessment at one month after trial registration, 405 (74%) patients reported that their participation in the trial was worthwhile and 139 (26%) answered that participating in the trial was not worth it. There was no difference in OS between the two groups (median 12.5 vs. 11.7 months, p = 0.09). Among 521 patients who were alive without progressive disease and completed the assessment, 392 (75%) reported satisfaction while 129 (25%) reported not satisfied. PFS was more favorable in patients who reported satisfaction with their participation compared to those who did not (median 4.8 vs. 3.9 months, respectively, p = 0.01). Conclusions: Although patient satisfaction did not translate into an overall survival benefit, progression free survival was more favorable in patients who felt their participation was worthwhile. This research supports improving design of future oncology trials by incorporating empathetic and psychosocial support for oncology patients during clinical trial participation. Support: U10CA180821, U10CA180882, UG1CA189823.
IMPACT OF ANGIOGRAPHIC PATTERNS OF IN-STENT RESTENOSIS ON LONG-TERM CLINICAL OUTCOMES IN PATIENTS TREATED WITH COBALT-CHROMIUM EVEROLIMUS-ELUTING STENT
Authors: Takashi Hiromasa, Shoichi Kuramitsu, Seiichi Hiramori, Kyohei Yamaji, Takenori Domei, Makoto Hyodo, Yoshimitsu Soga, Shinichi Shirai, Kenji Ando
Journal: Journal of the American College of Cardiology (2020)
PD-L1, B7-H3, and PD-1 expression in immunocompetent versus immunosuppressed patients with advanced cutaneous squamous carcinoma (cSCC).
Authors: Vinod Varki, Olga B. Ioffe, Soren Bentzen, Ashley L Cellini, Josephine Louella Feliciano, Dan Paul Zandberg
Journal: Journal of Clinical Oncology (2016)

9576 Background: Co-signaling molecules PD-L1, B7-H3, and PD-1 play a key role in tumor immunology. However their expression has not been characterized in cSCC. Methods: Weretrospectively analyzed 70 cases of cSCC treated with surgical resection between 2012 and 2015. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 (PD-L1%) and B7-H3 (B7-H3%) (Abcam), density of peri and intratumoral CD8 T cells (CD8 density) and proportion of CD8 T cells expressing PD-1 (CD8-PD-1%) (Abcam). Statistical analysis was performed using non-parametric Mann-Whitney test, chi-square test and Spearman’s rank correlation, Rs. Results: Of 70 cases, 45 were immunocompetent, 25 immunosuppressed (13 organ transplant, 8 HIV+, 4 other). Defining positive expression as > 5%, 26% of all tumors were positive for PD-L1, 85% for B7-H3, and 80% had CD8 T cells that co-expressed PD-1. Amongst immunocompetent patients, 27% of tumors were PD-L1 positive, 88% B7-H3 positive, and 80% had CD8 T cells that co-expressed PD-1. B7-H3% was significantly higher (Median 60% vs. 28%, p = 0.025) in immunocompetent vs. immunosuppressed patients, however there was no significant difference in PD-L1%, CD8 density, or CD8-PD-1%. When factoring in cause of immunosuppression, again only B7-H3% was significantly different between groups. Tumors from HIV+ patients lacked PD-L1 expression, had lower B7-H3% (Median 2.5% vs. 60%, p = 0.007), and higher CD8 density (Median 75% vs. 40%, p = 0.039) than tumors in immunocompetent patients. PD-L1% increased with increasing CD8 density (Rs = 0.31, p = 0.011) and CD8-PD-1% (Rs = 0.28 , p = 0.02). There was no correlation between B7-H3% and PD-L1%, CD8 density, or CD8-PD-1%, nor was there any correlation between tumor grade and these parameters. Conclusions: SCCs showed expression of PD-L1 and B7-H3, as well as PD-1 expression on peri- and intra-tumoral CD8 T cells. Tumor B7-H3 expression was significantly higher in immunocompetent vs. immunosuppressed patients, largely driven by very low expression in HIV+ patients.
Frequent expression of androgen receptor (AR) on tumor cells of muscle-invasive (MIUC) and metastatic urothelial carcinoma (mUC): Insights for clinical research.
Authors: Maurizio Colecchia, Salvatore Lo Vullo, Patrizia Giannatempo, Daniele Raggi, Federica Perrone, Nicola Nicolai, Mario Catanzaro, Davide Biasoni, Tullio Torelli, Luigi Piva, Silvia Stagni, Roberto Salvioni, Filippo G. De Braud, Giuseppe Procopio, Luigi Mariani, Andrea Necchi
Journal: Journal of Clinical Oncology (2017)

e16019 Background: Advanced UC treatment is being revolutionized by immunotherapy (IT). However, &lt; 30% of patients (pts) will benefit from IT, and additional therapeutic targets are needed. Findings from analyses supporting an investigator-led, AR-based clinical research program are presented. Methods: From 09/2015, we collected the archival tissue blocks from pts who have been treated or consulted at our center and received platinum-based chemotherapy (CT) for MIUC or mUC. Immunohistochemistry (IHC) was performed on 3µm slides using mouse anti-human AR monoclonal Ab (Dako, clone AR441). ≥1% cutoff for AR+ IHC of tumor cells (TC) was used. AR-expressing pts were further stratified as follows: 1-5%, 5-25%, and 25-100%. Univariable (UVA) and multivariable (MVA) Cox models for overall survival (OS) were fitted, the latter adjusted for clinical stage (MIUC vs mUC), presence of visceral metastases, platinum CT type. OS was calculated from the date of first administration of CT. Exploratory PD-L1 co-expression, by TC or stroma (SP142 Ab, 1% cutoff), was analyzed in all pts. Results: 105 pts (46 MIUC and 59 mUC) had their tumor stained. 80 (76.2%) had bladder primary tumor, 85 (80.9%) had pure UC. 59 received cisplatin and 46 carboplatin. Overall, 37 pts (35.2%) had AR-expressing TC, 17 (16.2%) with ≥25% expression. Cox models were built on 93 pts with follow-up duration of ≥6 months. AR-expressing was equally distributed between MIUC and mUC pts (44.4% and 55.6%). On UVA, AR expression was not associated with OS, neither dichotomizing AR+/AR- pts (p = 0.477) nor after accounting for AR-positivity strata (p = 0.845). The same results were confirmed on MVA (p = 0.505 and p = 0.875). In AR+ vs. AR- pts, PD-L1 was equally expressed in the stroma (67.5 vs 57.9%) but less expressed by TC (39.4% vs 52%). Conclusions: AR is frequently expressed on TC of pts with MIUC and mUC, and AR expression does not seem to be associated with OS in these pts. AR pathway is worthy of clinical studies to synergistically act with anti-PD-L1 therapy. AR sequencing and FISH analysis in positive pts is ongoing, and a clinical program of a named-basis administration of antiandrogen therapy has started at our center.
Length of time to conduct goals of care visits.
Authors: Sofya Pintova, Cardinale B. Smith, Kerin B. Adelson, Jason Parker Gonsky, Natalia Egorova, Rebeca Franco, Nina A. Bickell
Journal: Journal of Clinical Oncology (2018)

10107 Background: Oncologists report that time to conduct a goals of care (GoC) discussion is a barrier. We studied the relationship of GoC discussion and visit times at different type hospitals. Methods: At community, academic, municipal and rural hospitals, we recruited & randomized solid tumor oncologists & their newly diagnosed advanced cancer patients with < 2 year prognosis to participate in a RCT, testing a coaching model of communication skills training. Patients were surveyed after post-imaging visits. These visits were audiotaped and median encounter time recorded. We define GoC discussions as patient report that their doctor talked about preferences for cancer treatment and clarified things most important to them given their illness. Analyses were done with Kruskal-Wallis and Wilcoxon tests. Results: For 22 randomized oncologists in the study, 137 post-imaging encounters were audiotaped. The median face-face time oncologists spent during a GoC encounter with an advanced cancer patient was 15 minutes. Encounter times when GoC discussions were expected varied between the four sites, ranging from 9.5 minutes to 18 minutes, p = 0.05. The encounters where no GoC discussions occurred were longer, taking 16.5 minutes vs 13 minutes, p = 0.05. Visits that took place after progression of disease took longer, 18 minutes vs 13 minutes, p = 0.006. Conclusions: Visit times vary by hospital type and average 15 minutes. With disease progression, visit time is longer. Despite physician perceptions, GoC discussions do not lengthen visits. Clinical trial information: NCT02374255.Hospital (N) Encounter Time* Minutes (range) Encounter Time GoC Discussion Occurred (+) Minutes (range) Encounter Time No GoC Discussion Occurred (-) Minutes (range) p value Encounter Time Progression of Disease Minutes (range) Encounter Time No Progression of Disease Minutes (Range) p value Overall (137) 15 (4-40) 13 (4-40) 16.5 (4-40) 0.05 18 (12-22) 13 (10-19) 0.006 Community (10) 9.5 (4-38) 9.5 (4-38) NA - 18 (9-38) 9 (5-12) 0.14 Academic (98) 15 (4-40) 13 (4-40) 15 (4-33) 0.18 17 (12-20) 13 (10-20) 0.16 Municipal (15) 12 (6-40) 10 (6-35) 14.5 (7-40) 0.42 24 (19-28) 10 (7-17) 0.09 Rural (14) 18 (10-34) 18 (10-34) 18 (10-34) 0.75 22 (22-34) 17 (12-23) 0.12 *p = 0.05
Use of immunotherapy with patient-specific antigens to select tumor specific T cell receptor (TCR) in cancer patients.
Authors: Yanyan Han
Journal: Journal of Clinical Oncology (2016)

e14529 Background: Adoptive T cell transfer was recently more and more often used to treat cancer patients who have failed in standard therapies. An immunotherapy named MASCT (Multiple Antigen Stimulating Cellular Therapy) was applied to cancer patients, which is composed of patient-specific antigen pulsed dendritic cells (DCs) and autologous tumor specific T lymphocytes. Methods: Patients' autologous T cells were co-cultured with mature DCs pulsed with multiple tumor antigens for 7-9 days before infusion back. The tumor antigen specific immune responses in patients were examined during the treatment, and the antigens were selected accordingly. The tumor specific T cell receptor (TCR) would be further cloned from these patients who have demonstrated both immunological and clinical responses. Results: A human papilloma virus (HPV) positive cervical cancer patient with bone metastasis on the right sacroiliac joint have repeatedly received treatment of MASCT. Specific responses against tumor antigens were detected in this patient's PBMCs by IFNγ ELISPOT assay, such as telomerase, CEA, and HPV18/58. Based on patient’s specific immune response, we adjusted her antigen peptide pool by saving the antigens, which had induced specific responses and removed the peptides that did not. The adjusted antigen pool clearly further boosted the specific responses.Moreover, this patient was evaluated as partial remission by whole body bone SPECT after MASCT treatment with patient-specific antigens. Therefore, we are now trying to sort the CEA and telomerase specific CD8+ T cells from this patient and clone the two TCRs from the T cells. Conclusions: Our study provides a promising method to clone tumor specific TCRs from cancer patients, who have shown enhanced immunological responses as well as clinical benefits after being treated by MASCT with patient-specific antigens.
Abstract 16248: Attitudes Towards Genetic Testing and Genome Sequencing in the MI GENES Randomized Control Study
Authors: Sharma Kattel, Mostafa Jamaliramin, Sherry-Ann Brown, Hayan Jouni, Erin Austin, Iftikhar J Kullo
Journal: Circulation (2016)

Background: Genetic testing and genome sequencing are being increasingly used in the clinical setting. However, patients’ attitudes towards genetic testing and genome sequencing after disclosure of...
Disentangling the association between statins, cholesterol, and colorectal cancer: A nested case-control study.
Authors: Ronac Mamtani, James D. Lewis, Frank I. Scott, Tariq Ahmad, David S Goldberg, Jashodeep Datta, Yu-Xiao Yang, Ben Boursi
Journal: Journal of Clinical Oncology (2016)

3609 Background: Prior studies have found an association between statin use and reduced risk of colorectal cancer (CRC). We hypothesized that these findings may be due to systematic bias, and examined the independent association of CRC risk with statin use, serum cholesterol, and change in cholesterol concentration. Methods: 22,163 colorectal cancer cases and 86,538 matched controls between 1995 and 2013 were identified within a UK primary care database. Conditional logistic regression estimated CRC risk with statin use, serum total cholesterol (mmol/L), and change in total cholesterol level. Results: We confirmed a decreased risk of CRC with statin use (long-term: OR, 0.95; 95% CI, 0.91-0.99; short-term: OR, 0.92; 95% CI, 0.85-0.99). However, to assess whether the observed association may result from indication bias, a subgroup analysis was conducted among patients prescribed a statin. In this subgroup (n = 5,102 cases, n = 19,032 controls), the risk of CRC was not significantly different among those who continued statin therapy and those who discontinued (OR, 0.98; 95% CI, 0.79-1.22). Increased serum cholesterol was independently associated with decreased risk of colorectal cancer (OR, 0.89 per mmol/L increase; 95% CI, 0.87-0.91). Decreases in serum total cholesterol > 1 mmol/L ≥ 1 year prior to cancer diagnosis were associated with subsequent CRC (statin users: OR, 1.25; 95 CI%, 1.03-1.53; nonusers: OR, 2.36; 95 CI%, 1.78-3.12) Conclusions: Although the risk of CRC was lower in statin users versus nonusers, no difference was observed among those who continued versus discontinued statin therapy, suggesting the potential for indication bias. The association between decreased serum cholesterol and CRC risk suggests a cholesterol-lowering effect of undiagnosed malignancy. Further studies are needed to assess the clinical utility of serum cholesterol as a biomarker for risk or early detection of CRC.
A multicenter, single arm phase II trial of a small molecule immune-modulator icaritin: Safety, overall survival, immune dynamics, and PD-L1 expression in advanced hepatocellular carcinoma.
Authors: Yan Sun, Qing Li, Jian-Ming Xu, Jun Liang, Ying Cheng, Shu Li, Limin Zheng, Bin Ye, Kun Meng, Shukui Qin
Journal: Journal of Clinical Oncology (2018)

4077 Background: HCC was characterized with high heterogeneity and immune "tolerogenic". Despite of immune checkpoint inhibitors have demonstrated promising results with improved overall survival, a significant fraction of advanced HCC patients are still left with limited treatment options and poor survival. The purpose of this study is to determine the safety, clinical activity and immune dynamic biomarkers of a small molecule icaritin, IL-6/STAT3 immune-modulator in advanced HCC. Methods: Major eligibility criteria include histologically confirmed unresectable HCC patients with Child-Pugh Class A or B liver function. Total of 70 advanced HCC patients were enrolled and administrated with 600 mg b.i.d. Primary endpoints were TTP, secondary endpoints were safety, OS, and DCR. Local disease control was defined as no progressive disease (PD) by RECIST. Kaplan-Meier analysis was utilized for OS assessment. Immune dynamic of NLR, IL-6 and baseline PD-L1 expression of immune cells was evaluated, retrospectively. Results: There was no ≥grade III drug related AE observed in all enrolled 70 advanced HCC patients. Objective response evaluation in per-protocol population showed PR (1.6%), SD (32.8%) and PD (59.0%) and median overall survival (OS) 254day (95% CI, 172-296). DCR was achieved 34.4% (95% CI, 22.7-47.7%); Median OS for the PD-L1-positive (n = 9) and negative (n = 24) subgroups were 389 (95% CI, 80-522) vs. 286.5days (95%CI, 135-482), for IL-6-advantage (n = 24) and disadvantage (n = 16) subgroups were 366.5 (95% CI, 277-566) vs. 157days (95% CI, 125-254), for NLR-advantage (n = 27) and disadvantage (n = 23) subgroups were 295(95% CI, 235-509) vs. 178days (95% CI, 135-296), respectively. Conclusions: Icaritin has demonstrated its favorable clinical safety and immune-modulation clinical efficacy. The improved OS was implicated in the subgroups of advanced HCC patients including PD-L1-positive immune cell expression. Both safety and immune-response efficacy are warranted for the phase III trial. Clinical trial information: NCT01972672.
Using real world data to evaluate overall survival in PD1-treated vs. standard of care metastatic melanoma patients.
Authors: Purvi Dev-Vartak, Xinyan Yu, Fa-Qiang Liu, Paul Cariola, Jeffrey Hodge, Vijayavarman Gopalakrishnan, Rolin L Wade
Journal: Journal of Clinical Oncology (2018)

e21606 Background: Metastatic malignant melanoma has a low 5-year survival rate and responds poorly to most standard of care treatments. We wanted to understand the impact of programmed death-ligand 1 (PD-1) inhibitors on overall survival in patients with metastatic melanoma in a real world setting. Methods: Using the oncology panel in a proprietary US longitudinal medical and pharmacy claims database, we evaluated the 12- and/or 24-month survival of patients with previously treated (2L+) metastatic melanoma (ICD 10 - C43.xx; plus C77.xx-C79.xx) and previously untreated (1L) metastatic melanoma. Those receiving 2L+ treatments were treated between Sept. 2014 and Sept. 2015 (cohort 1) and those receiving 1L treatment were treated between Oct. 2015 and Oct. 2016 (cohort 2). All patients were > = 18 years of age, and cohorts 1 and 2 were followed up to 2 years and 1 year post-index period through Nov. 2017, respectively. Kaplan-Meier survival analysis was conducted using a previously validated method to reference death information[i] and patients receiving pembrolizumab or nivolumab were compared to those receiving standard of care. Results: Cohort 1 and 2 consisted of 398 and 1159 patients, respectively, with 274 and 814 receiving PD-1 therapy. Cohort 1 was followed for up to 24 months and cohort 2 for up to 12 months, showing a significant difference in survival (p < 0.0007 cohort 1, p < 0.0001 cohort 2, log-rank test) (Table 1). Conclusions: Using a longitudinal medical and pharmacy claims database, we found a significant 12 and 24-month survival benefit in metastatic melanoma patients treated with the PD-1 inhibitors, pembrolizumab or nivolumab. These insights suggest that this type of database can be explored for patient survival studies. [1] https://www.ispor.org/ScientificPresentationsDatabase/Presentation/75048Table 1. Survival analysis Time from Index Survival Percentage Cohort 1 (2L+) Cohort 2 (1L) Index Sept. 2014 – Sept. 2015 Index Oct. 2015 – Oct. 2016 PD-1 treated Standard of Care Drugs PD-1 treated Standard of Care Drugs n = 274 n = 124 n = 814 n = 345 180 days 73.32% 61.29% 79.73% 74.49% 360 days 60.09% 40.32% 69.38% 60.84% 540 days 50.79% 34.68% 720 days 45.87% 32.26%
Abstract 13874: Poor Quality of Warfarin Therapy is Associated With Elevated Risk Of Myocardial Infarction in Patients With Atrial Fibrillation. Results From the FinWAF Registry With 54568 Patients
Authors: Pekka Raatikainen, Jussi Niiranen, Pasi Korhonen, Juha Mehtälä, Houssem Khanfir, Riitta Lassila, Mika Lehto
Journal: Circulation (2015)

Background: A bulk of data indicates that atrial fibrillation (AF) has serious adverse prognostic implications among patients with myocardial infarction (MI). However, the impact of the quality of vitamin K antagonist (VKA) therapy on the incidence of MI among patients with AF is largely unknown. Patients and Methods: We evaluated the association between the quality of VKA therapy (time in therapeutic range, TTR) and risk of MI in a cohort of 54568 patients using warfarin for AF (FinWAF). In the FinWAF database information from several Finnish nationwide registries are linked through the civil registration number of the patients. Results: The number, crude rate and adjusted hazard ratio (HR) of MI among patients with AF and various TTR levels are presented in Table 1. The risk of MI was significantly higher among patients with TTR&lt;50% than in the reference population (TTR=60-70). In contrast, patients with TTR&gt;80 were less likely to have MI during the mean follow-up of 2.4 years (SD 1.7, range 0.0-5.0). Moreover, the risk of MI was clearly higher among those with previous MI (HR 7.0. 95% confidence limits 6.4-7.8). Conclusions: Our data demonstrated an indirect relationship between TTR values and incidence of MI in patients with AF. This novel finding emphasize the importance of high-quality warfarin management not only with regards to stroke but also to the risk of MI.