tbuckley/cabot-search huggingface dataset:
Results of a prospective randomized phase III T-SAR trial comparing trabectedin (T) <i>vs</i> best supportive care (BSC) in patients with pretreated advanced soft tissue sarcoma (ASTS): A French Sarcoma Group (FSG) trial.
Authors: Axel Le Cesne, Jean-Yves Blay, Didier Cupissol, Antoine Italiano, Corinne Delcambre, Nicolas Penel, Nicolas Isambert, Christine Chevreau, Emmanuelle Bompas, Francois Bertucci, Loic Chaigneau, Sophie Piperno-Neumann, Sébastien Salas, Maria Rios, Cecile Guillemet, Jacques Olivier Bay, Isabelle Laure Ray-Coquard, Leila Haddag, Olivier Mir, Stéphanie Foulon
Journal: Journal of Clinical Oncology (2018)

11508 Background: With the exception of a study in translocation-related STS (Kawai, 2015), T has never been compared to BSC in a study including patients (pts) with all sarcoma histotypes. The efficacy, safety and quality of life of T vs BSC as second or later treatment line were evaluated in pts with ASTS in a multicenter FSG trial. Methods: The study enrolled pts ≥18 years of age with histologically proven ASTS who progressed after at least 1 anthracycline-containing regimen (≤3 previous chemotherapy (CT) lines), stratified by L-STS (lipo-leiomyosarcoma) and non L-STS and with a WHO performance status score 0-1. Pts were randomized 1:1 to receive either T (1.5 mg/m2 24h every 3 weeks) or BSC until disease progression (PD), unacceptable toxicity, or patient's request. Pts allocated to BSC could cross over to T at PD. The primary endpoint was progression-free survival (PFS). Results: Between January to November 2015, 103 pts (median 65 yrs (range 22-84), grade 3 ASTS in 57% of cases, median number of 1 prior CT lines) were enrolled by 16 FSG centers, 52 in the T arm and 51 the BSC arm. Pts with L-STS and non L-STS represented 60% and 40% of pts, respectively. Two pts refused to be allocated in the BSC arm and received other CT. The objective response rate (ORR) in the T arm was 11.8%, all observed in the L-STS group (ORR: 18.8% in L-STS). 23% of pts in the T arm received more than 9 cycles of T. The median PFS were 1.5 months (m) in the BSC arm and 3.1m in the T arm (HR: 0.39, p < 0.0001). In the L-STS cohort, the median PFS were 1.4m and 5.1m in the BSC and T arm (HR: 0.29, p < 0.0001), respectively, whereas in the non L-STS group they were 1.5m and1.8 m (p = 0.16). A cross-over was performed in 92% of pts included in the BSC arm. By After a median follow-up of 25.7 months, the differences on OS were not statistically significant between the two arms, 13.6 m vs 10.8 m in the T and BSC arms respectively (p = 0.86). Conclusions: This study met its first endpoint as a preplanned PFS analysis showed a significant improvement in median PFS with T over BSC in pts with pretreated ASTS of multiple histologies. L-STS pts benefit the most from T therapy in terms of prolonged tumor control. Clinical trial information: NCT02672527.
Real-world use of epoetin zeta compared to guidelines for chemotherapy-induced anemia.
Authors: Florian Scotte, Kamel Laribi, Christian Gisselbrecht, Isabelle Laure Ray-Coquard, Emna Kasdaghli, Dominique Spaeth
Journal: Journal of Clinical Oncology (2016)

e18066 Background: The management of chemotherapy-induced anemia (CIA) by erythropoiesis-stimulating agents (ESAs) is well established, with EU and US guidelines advising their use to reduce red blood cell transfusions and improve health-related quality of life. The SYNERGY study investigated the use of epoetin zeta (Retacrit, Hospira, a Pfizer company) with and without iron supplementation in clinical practice in France. Methods: This observational, longitudinal, prospective, multicenter study was conducted in France, from a representative, random sample of oncologists and hematologists. The primary aim was to assess anemia response to epoetin zeta with and without iron supplementation; secondary objectives included current practice in management of CIA, monitoring of iron status and iron supplementation. The study included adults with CIA, with solid tumors or hematological malignancies, eligible for treatment with epoetin zeta, followed-up at 12–16 weeks. Results: Of 195 physicians who responded, 51.8% initiated ESA treatment at Hb levels of 8–9.9 g/dL and 41.0% at Hb levels of 10–11.9 g/dL. Management of CIA differed between physicians who routinely performed iron work-ups (55.9%), as recommended by ESMO and NCCN, and those who did not (44.1%) (Table). Conclusions: Use of epoetin zeta in real-world practice follows EU guidelines, except in performing routine iron work-up, which could identify patients with functional iron deficiency who can benefit from IV iron supplementation. Clinical trial information: NCT02158169.Routine iron work-up? Yes No Iron work-up data taken into account for CIA management? Yes: 95.4% Yes: 58.5% Routine combination of iron supplementation and ESA? Yes: 31.2% Yes: 16.5% Preferential route of iron administration IV: 62.0% Oral: 36.1% IV: 49.4% Oral: 46.8%
Survival outcomes among young small cell lung cancer (SCLC) patients and insurance status: A SEER analysis 2007-2014.
Authors: Qian Wang, Yaning Zhang, Changchuan Jiang, Siddharth Kunte, Medhavi Gupta, Lei Deng, Zhengrui Xiao, Yuzhou Liu, Stuthi Perimbeti, Robert Michael Daly
Journal: Journal of Clinical Oncology (2018)

e20566 Background: Lung cancer is the second most common cancer and the leading cause of cancer-related death in the US. Of 222,500 newly diagnosed lung cancer cases, 10-15% are SCLC. The average 5-year survival rate of SCLC is poor ranging from 2-31% based on stage. Among elderly SCLC patients, it has been showed that the uninsured and Medicaid were less likely to receive guideline-concordant therapy and have higher overall mortality. We aim to explore the influence of health insurance and the Affordable Care Act (ACA) on the treatment and survival of younger SCLC patients. Methods: SEER 18 Program from 2007-2014 was used to identify SCLC patients less than 65 years of age. Age, gender, race, education, income, insurance, tumor grade, stage and treatment were analyzed. Subjects who developed secondary cancers were excluded. Logistic regression and Cox proportional hazards modeling were employed using SAS 9.4. Results: A total of 12,551 patients were included. Compared to insured patients, those who were non-Hispanic Black, Hispanic, with advanced stage disease, less than college education and annual income less than 55K were more likely to be Medicaid or uninsured. Medicaid and uninsured lung cancer patients were significantly less likely to be treated with chemotherapy and/or radiotherapy compared to insured patients regardless of stage at diagnosis. Among extensive stage disease, Medicaid and uninsured status was associated with 24% (95% CI 1.18-1.31) and 23% (95% CI 1.14-1.33) higher overall mortality compared to insured. This difference did not change after 2010. Conclusions: Medicaid SCLC patients had the worst overall and cause-specific survival compared to insured and uninsured. This remained unchanged before and after 2010 when ACA became effective. As ACA prohibits denying coverage or charging higher premium for pre-existing lung cancer, prohibits insurance plans from denying certain costs related to cancer clinical trial participation, and requires insurers to cover low dose-CT screening without copay, future studies are needed to explore whether ACA will have a beneficial impact on young SCLC patients given the high overall mortality of this group.
A Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Patients with Castration-resistant and Neuroendocrine Prostate Cancer: Efficacy and Biomarkers
Authors: Himisha Beltran, Clara Oromendia, Daniel C. Danila, Bruce Montgomery, Christopher Hoimes, Russell Z. Szmulewitz, Ulka Vaishampayan, Andrew J. Armstrong, Mark Stein, Jacek Pinski, Juan M. Mosquera, Verena Sailer, Rohan Bareja, Alessandro Romanel, Naveen Gumpeni, Andrea Sboner, Etienne Dardenne, Loredana Puca, Davide Prandi, Mark A. Rubin, Howard I. Scher, David S. Rickman, Francesca Demichelis, David M. Nanus, Karla V. Ballman, Scott T. Tagawa
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may develop de novo or as a mechanism of treatment resistance. N-myc is capable of driving NEPC progression. Alisertib inhibits the interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc signaling, and suppressing tumor growth. Patients and Methods: Sixty men were treated with alisertib 50 mg twice daily for 7 days every 21 days. Eligibility included metastatic prostate cancer and at least one: small-cell neuroendocrine morphology; ≥50% neuroendocrine marker expression; new liver metastases without PSA progression; or elevated serum neuroendocrine markers. The primary endpoint was 6-month radiographic progression-free survival (rPFS). Pretreatment biopsies were evaluated by whole exome and RNA-seq and patient-derived organoids were developed. Results: Median PSA was 1.13 ng/mL (0.01–514.2), number of prior therapies was 3, and 68% had visceral metastases. Genomic alterations involved RB1 (55%), TP53 (46%), PTEN (29%), BRCA2 (29%), and AR (27%), and there was a range of androgen receptor signaling and NEPC marker expression. Six-month rPFS was 13.4% and median overall survival was 9.5 months (7.3–13). Exceptional responders were identified, including complete resolution of liver metastases and prolonged stable disease, with tumors suggestive of N-myc and Aurora-A overactivity. Patient organoids exhibited concordant responses to alisertib and allowed for the dynamic testing of Aurora–N-myc complex disruption. Conclusions: Although the study did not meet its primary endpoint, a subset of patients with advanced prostate cancer and molecular features supporting Aurora-A and N-myc activation achieved significant clinical benefit from single-agent alisertib.
Peroral endoscopic myotomy and peroral endoscopic pyloromyotomy as a single procedure for concomitant achalasia and gastroparesis
Authors: Denisa Erhartova, Zuzana Vackova, Rastislav Hustak, Julius Spicak, Jan Martinek
Journal: Endoscopy (2018)

Peroral endoscopic myotomy (POEM) has become a standard treatment for achalasia, and peroral endoscopic pyloromyotomy (G-POEM) represents an emerging endoscopic method in the management of refractory gastroparesis. We present a successful procedure combining POEM and G-POEM in one session in a patient with concomitant achalasia and refractory gastroparesis. Although G-POEM and subsequent POEM (after 4 days) have already been performed in one patient [1], a simultaneous myotomy on the lower esophageal sphincter (LES) and the pyloric muscle within a single procedure has not been described.
TCT-57 Hemodynamic and Functional Improvement Following Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: Initial Experience at a High Volume Pulmonary Thromboendarterectomy Center
Authors: Ehtisham Mahmud, Alessandro Maolo, David Poch, Lawrence Ang, Mitul Patel, Nick Kim
Journal: Journal of the American College of Cardiology (2018)
Do immune-related adverse effects predict better outcomes in lung cancer?
Authors: Prashant Mukesh Jani, Ariel Sandhu, Amir Kamran, Gurleen Pasricha, Sai Krishna Patibandla, Amulya Yellala, Amy Tang, Gene Grant Finley
Journal: Journal of Clinical Oncology (2018)

e15067 Background: Immune Checkpoint Inhibitors (IO) produce an unusual pattern of side effects not seen with traditional treatment. Such immune-related adverse events (irAE) occur in many treatment settings, and are associated with survival benefit in melanoma and NSCLC. We report herein on our experience with IO therapy in advanced lung cancer patients in a large health care system including community cancer centers and tertiary referral sites. Methods: We conducted a retrospective analysis of 219 lung cancer patients who received at least 1 cycle of IO therapy at Allegheny Health Network (AHN) between 7/1/2015 and 11/30/2017. A landmark analysis assessing PFS and OS at 4, 6 and 8 weeks was conducted. PFS was calculated based on radiographic progression, clinical deterioration or death. Kaplan-Meier survival analysis and a log-rank test for equality were performed for patients who experienced irAE. Multivariate Cox proportional-hazard model was used to evaluate the relationship between irAE within 4 weeks of immunotherapy and overall survival, along with parallel analyses occurring within 6 and 8 weeks of treatment. Results: The study population comprised 127 adenocarcinomas, 56 squamous cell carcinomas, 19 small cell carcinomas and 17 with other histology. 39 patients received IO 1st line, 140 in 2nd line, and 39 in ≥ 3rd line. 57 patients had irAE and 15 of these occurred within 4 weeks of treatment. 31 irAE were grade 1 or 2; 26 were grade 3 or higher. In the univariate analysis, patients experiencing toxicity within 4 weeks of receiving IO had a nearly two-fold increase in mortality risk (HR = 2.1, 95% CI 1.07-3.98, p = 0.03). Median OS at landmark analysis at 8 weeks was 212 days in the group with irAE vs. 446 days for those without irAE. Statistical significance of differences in PFS and OS was not retained in the multivariate regression model after adjusting for age, diagnosis type, and number of cycles of therapy. Conclusions: Previous reports have suggested an association between irAE and survival in patients with NSCLC. Our data from a diverse health care enterprise showed no association between irAE and survival in lung cancer.
The role of clinical and surgical factors characterizing longterm-survival in ovarian cancer.
Authors: Hannah Woopen, Ioana Braicu, Oliver Hunsicker, Silvia Darb-Esfahani, Joanna Glajzer, Aygun Babayeva, Jalid Sehouli
Journal: Journal of Clinical Oncology (2016)

e17059 Background: Ovarian cancer is the leading cause of mortality of all gynecological cancers. Within the first years after diagnosis 75-80% of patients relapse and die from the disease. However, there are ovarian cancer patients who survive substantially longer. The aim of this project is to characterize these longterm-survivors (LTS). Methods: The data were prospectively obtained in our validated Tumorbank Ovarian Cancer (TOC) starting in 2000. LTS have been defined as patients surviving at least 8 years after first diagnosis. The control group consisted of patients who died within the first 5 years and who underwent surgery within the same timeframe at our institution. Groups were compared regarding clinical features and tumor spread before and after propensity score matching. Results: A total of 90 LTS and 179 controls were identified. Before propensity score matching, main differences between the two groups were observed in respect to FIGO stage and postoperative tumor residuals: Patients in the LTS group were diagnosed more frequently in earlier FIGO stages (43% vs. 8% FIGO I/II and 57% vs. 92% FIGO III/IV, p < 0.0001) and complete tumor resection was more frequently achieved (91% vs. 55%, p < 0.0001). The presence of ascites (61% in LTS vs. 79 % in controls, p = 0.0001) and lymph node involvement (N0 in 56% LTS vs. 29% controls, p < 0.0001) were less frequent in the LTS group. Recurrent disease was less common (29% LTS vs. 81% controls, p < 0.0001). In contrast, there was no significant difference between LTS and controls regarding age, grading and histology. After matching for FIGO stage, recurrent disease status, macroscopically complete tumor debulking, high-grade serous histology and age, there were no differences in tumor spread, ascites, lymph node involvement and surgical procedures between the two groups. Conclusions: Postoperative tumor residuals and FIGO stage seem to be the most important prognostic factors even in longterm-survivors. Nevertheless, other factors such as genetics, immune system and lifestyle may substantially influence longterm-survival. Ongoing research projects are focusing on these aspects.
P01.047 Improving quality of life in glioma patients: platform for exchange of patients’ expertise in TTFields practice
Authors: A Kessler, E Jentschke, J Weiland, V Dufner, N Lilla, T Linsenmann, T Westermaier, C Hagemann, R Ernestus, M Löhr
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) atients nd their elatives (PaR) face tremendous distress and psychological burden due to limited survival and neurological/neuropsychological deficits. Tumor Treating Fields (TTFields, alternating electric fields at 200 kHz) are a novel therapy for patients with newly diagnosed and recurrent GBM. TTFields allows PaR to actively contribute to therapy, but does require concerted attention. Additionally, PaR have to adapt to social exposure due to the visible transducer arrays. Our clinical experience shows an urgent need for personal exchange in communicating with GBM patients; especially as expressed by female patients. Establishing patient-driven support groups is limited by the rapid clinical progression of GBM. The aim of this study was to systematically evaluate the needs of PaR to implement a platform for personal interaction with focus on TTFields treatment, and to analyze the benefits experienced by PaR. Questionnaires to evaluate PaR’s needs regarding meeting other PaR included: preferences for time, frequency, and maximal travel distance, type and frequency of the desired professional support. Quality-of-life and emotional function were determined two weeks before and after implementing this program by the questionnaires PHQ-2 (level of depression) and GAD-2 (level of anxiety). Additionally, perception of everyday life restriction and social exposure were analyzed by a 5-digit-scale. We assessed 19 PaR using TTFields at our department. 92% expressed general interest, with 86% wanting to meet other patients, relatives (64%), their physician (73%) and psychologist (59%). Therefore, we established a meeting outside of the hospital, accompanied and supported by the treating physician and psychologist. Two weeks after the meeting, no significant changes were detected in levels of depression or anxiety in comparison to levels before the meeting. Interestingly, the meeting resulted in a strong trend towards improved perception regarding social exposure, reducing the median level from “medium” to “low” (3 points (range 2–3) before to 2 points (range 1–3) in median after the meeting, p=0.058). Similar results were obtained for perception of everyday life (p=0.182). This pilot trial indicates that a communication platform for TTFields patients improves the perception of social exposure and everyday life, while simultaneously meeting the assessed PaR’s needs. Thus, we suggest implementing such a concept into clinical routine to improve patients’ quality-of-life.
Has the PD-L1 expression in tumor and immune cells the prognostic role in oral cavity squamous cell carcinoma?
Authors: Georgy M. Manikhas, Svetlana I. Kutukova, Natalia P. Beliak, Julia V. Ivaskova, Natalia V. Popova
Journal: Journal of Clinical Oncology (2018)

e18025 Background: Very important role in anticancer immunity shows the programmed death-ligand 1 (PD-L1) . The aim of our study was to examine the expression and prognostic value of PD-L1 in tumor and immune cells in patient with squamous cell carcinoma of oral cavity (OCSCC). Methods: We analysed tumor samples of 87 patients with OCSCC with stage I - IVB (56 men, 31 women; median age 59). We examined demographic data, clinical stage, tumor morphological characteristics and expression of PD-L1 in tumor and immune cells (clone BCDdx1020) by ICH (82 samples were acceptable). Results: The expression level in tumor cells varied from 0% to 70%: in 41.37% samples expression of PD-L1 were negative (0%), in 15.41% - from 1 to 4 % (low rate), in 31.25% - from 5 to 49% (moderate rate) and in 1.97% - more than 50% (high). In immune cells expression of PD-L1 varied from 0% to 15%: in 11,78% samples - negative (0%), in 55,68% - from 1 to 4% (low), in 22,95% - from 5 to 9% (moderate) and in 9,58% - >10% (high). In 8 samples with high level PD-L1 expression in tumor expression PD-L1 in immune cells was negative. Median OS of patients with negative rate of PD-L1 in tumor cells was mo 17.0 (95% CI 8.0-185.0), with low PD-L1 9.0 mo (95% CI 2.0-36.0), moderate PD-L1 13 mo (95% CI 7.5-9.0) and with high PD-L1 median OS significant not reach (M=55, 95% CI 26.0-84.0), p=0.05. Median OS of patients with negative PD-L1 in immune cells was 11.7 mo (95% CI 4.0-185.0), with low PD-L1 in immune cells - 13.3 mo (95% CI 7,5-34,5), with moderate PD-L1 - 15.8 mo (95% CI 9.0-16.5) and with hight PD-L1 - 17.4 mo (95%CI 3.0-37.0) with strong trend of increasing OS with rise of PD-L1 expression in immune cells. Correlation analysis shows trend of direct correction between PD-L1 expression in tumor cells and expression of CD-8 TIL: r=0.2499, p=0.0711. Conclusions: PD-L1 expression in tumor and immune cells could be favourable prognostic factors for oral cavity squamous cell carcinoma.
Characteristics of difficult-to-treat rheumatoid arthritis: results of an international survey
Authors: Nadia M T Roodenrijs, Maria J H de Hair, Marlies C van der Goes, Johannes W G Jacobs, Paco M J Welsing, Désirée van der Heijde, Daniel Aletaha, Maxime Dougados, Kimme L Hyrich, Iain B McInnes, Ulf Mueller-Ladner, Ladislav Senolt, Zoltan Szekanecz, Jacob M van Laar, György Nagy
Journal: Annals of the Rheumatic Diseases (2018)

Patients with difficult-to-treat rheumatoid arthritis (RA) remain symptomatic despite treatment according to current European League Against Rheumatism (EULAR) management recommendations. These focus on early phases of the disease and pharmacological management. We aimed to identify characteristics of difficult-to-treat RA and issues to be addressed in its workup and management that are not covered by current management recommendations.An international survey was conducted among rheumatologists with multiple-choice questions on disease characteristics of difficult-to-treat RA. Using open questions, additional items to be addressed and items missing in current management recommendations were identified.410 respondents completed the survey: 50% selected disease activity score assessing 28 joints >3.2 OR presence of signs suggestive of active disease as characteristics of difficult-to-treat RA; 42% selected fatigue; 48% selected failure to ≥2 conventional synthetic disease-modifying antirheumatic drugs (DMARDs) AND ≥2 biological/targeted synthetic DMARDs; 89% selected inability to taper glucocorticoids below 5 mg or 10 mg prednisone equivalent daily. Interfering comorbidities, extra-articular manifestations and polypharmacy were identified as important issues missing in current management recommendations.There is wide variation in concepts of difficult-to-treat RA. Several important issues regarding these patients are not addressed by current EULAR recommendations.