tbuckley/cabot-search huggingface dataset:
Effect of anticoagulation choice on survival for patients with myeloma being treated with a proteasome inhibitor.
Authors: Dianne Pulte, Nicole Gormley, Ann T. Farrell
Journal: Journal of Clinical Oncology (2018)

e20036 Background: Patients with myeloma have an increased risk of venous thromboembolism (VTE). Prior work examining the benefits and risks of anticoagulants in these patients has concentrated on the risk of VTE, treating death as a competing risk, and on immunomodulatory agents. Less is known about the effect of anticoagulants on survival outcomes in patients receiving a proteasome inhibitor (PI) and steroids. Methods: We examined overall survival (OS) and myeloma-specific survival (MSS) retrospectively in patients who participated in 1 of 2 trials submitted to the FDA for approval of a PI. Data extracted included anticoagulant, survival time, study arm, and cause of death. Kaplan-Meier curves were generated and mean survival extracted. P-values were determined using the log rank test. Results: A total of 929 patients were included (table). Mean OS for all participants was lower for patients who received anticoagulation of any type, heparin, ASA, or any combination. The point estimates for survival in patients receiving heparin and combination anticoagulant therapy were lower than those receiving ASA, but the differences were not statistically significant. When MSS was examined, no statistically significant difference was observed between groups, although a trend towards lower survival for those receiving any anticoagulant was observed. Conclusions: The use of anticoagulation in patients with myeloma receiving PI was associated with lower OS, but no difference in MSS. The differences in OS may be related to differences in comorbid issues, occurrence of VTE, or other issues. A prospective trial to examine survival could clarify this issue. Table: Mean survival in months for patients by anticoagulation type and subgroup Group (N) None (619) Any (310) Heparin (68) ASA (135) Other (47) Combination (60) OS All 45.4 38.3* 34.7* 39.3* 42.7 34.6* Newly diagnosed 46.6 40.0* 36.1* 41.7 43.5 36.5* Relapsed/refractory 23.0 16.2* NC NC NC NC Received PI 46.5 38.8* 38.1 38.6* 44.7 34.1* MSS All 52.1 49.3 49.7 48.6 44.1 45.4 Newly diagnosed 53.1 50.9 50.2 NC NC NC Relapsed/refractory 24.7 19.5 NC NC NC NC Received PI 53.7 48.6 49.4 47.4 46.2 47.8 *p≤0.05 for comparison with no anticoagulant NC = not calculated
TCT-178 Temporal trends in the utilization of Right Heart Catheterization (RHC) among recipients of Percutaneous Ventricular Assist Device (PVAD) in Acute Myocardial Infarction complicated by Cardiogenic Shock (AMI-CS)
Authors: Nikhil Nalluri, Varunsiri Atti, Varun Kumar, Deepak Asti, Mir Basir, Roman Royzman, Ruben Kandov, James Lafferty, Donald McCord, Srinivas Duvvuri, William O'Neill
Journal: Journal of the American College of Cardiology (2018)
Reference method for digital surface measurement of target lesions in vitiligo: a comparative analysis
Authors: N. Geel, D. Vandendriessche, E. Vandersichel, S. De Schepper, L. Grine, L. Mertens, V. Vandaele, F. Spoelders, M. Bekkenk, A. Wolkerstorfer, C.A. Prinsen, R. Speeckaert
Journal: British Journal of Dermatology (2018)

BackgroundObjective measurement of target lesions in vitiligo is important for clinical practice and trials, yet no preferred tool has been defined. Reported digital tools have shortcomings related to feasibility aspects and often lack information on validity, reliability and responsiveness. Moreover, studies are not yet based on ultraviolet (UV) photography.
Lapatinib efficacy according to metastatic sites in trastuzumab pretreated patients with HER2-positive metastatic breast cancer: An analysis form IntERB registry in the Czech Republic.
Authors: Peter Grell, Vit Kandrnal, Bortlicek Zbynek, Rostislav Vyzula
Journal: Journal of Clinical Oncology (2012)

e11072 Background: Lapatinib is an oral dual tyrosin kinase inhibitor of EGFR and HER2 and compared to trastuzumab penetrates to CNS. We evaluated efficacy and safety of lapatinib treatment according to different metastatic sites involvement using data from IntERB registry that has been initiated and run by Czech Society for Oncology and Institute of Biostatistics and Analyses at Masaryk University, Brno, Czech Republic. Methods: An analysis included 213 patients with HER2 positive metastatic breast cancer treated from January 2007 to September 2011. Lapatinib was mostly administered orally 1250mg/day with capecitabine (2000mg/m2 D1-14), 16 patients received lapatinib in monotherapy. All patients had experienced progression during prior trastuzumab based therapy. Results: Median age was 56 years (range 23 – 78). Median duration of lapatinib therapy was 20.6 weeks (range 1–146). Complete response was achieved in 13 patients (6.1%), partial response in 31 (14.6%), stable disease in 118 (55.4%). In 26 disease have progressed (12.2%); response could not be assessed in 25 patients (11.7%). PFS for whole group was 7.1 months (95% CI 5.9-8.5). Overall survival was 17.2m (95% CI 15.8-18.6), probability of 6m OS was 80.3% and 1-year OS was 64%. Metastatic sites specific survival was evaluated in 103 patients. CNS dissemination was initially diagnosed in 31 patients (30.1%), PFS in this group was 6.2m (95% CI 3.3-9.1), OS was not reached, 6-m OS was 67.3%. In non-CNS group (skeletal metastasis in 49.5%, lung 38.8%, hepatic 36.9%, lymphatic 17.5%, other 15.5%) was PFS 6.3m (95% CI 1.6-11.1), OS 22.0m (95% CI 15.3-28.8) and 6-m OS was 88.2%. Most common toxicities were diarrhea in 11.7% patients, rash/skin toxicity in 10.8%, nausea/vomitus in 5.2% and hepatotoxicity in 2.3%. No cardiac toxicity was reported. Therapy was discontinued due toxicity in 9.0%. Conclusions: Lapatinib in combination with capecitabine proved its efficacy in trastuzumab pretreated HER2 positive metastatic breast cancer. Even in patients with CNS involvement was achieved a notable PFS and OS, comparable to non-CNS group of patients. Therapy was well tolerated.
Toca 6: A phase 1b study of Toca 511 and Toca FC in patients with advanced solid tumors or lymphoma.
Authors: Jaime R. Merchan, Jordi Rodon Ahnert, Gerald Falchook, Derek Ostertag, Dalissa Tejera, Harry E. Gruber, Douglas J. Jolly, Jolene Shorr
Journal: Journal of Clinical Oncology (2018)

TPS2613 Background: Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector that selectively infects cancer cells. Toca 511 spreads through tumors, stably delivering an optimized cytosine deaminase (CD) gene that converts the prodrug, Toca FC (investigational, extended-release 5-FC), into 5-FU within the tumor microenvironment. Preclinical studies show 5-FU kills infected dividing cancer cells and diffuses and kills surrounding cancer cells, myeloid derived suppressor cells, and tumor associated macrophages, thus reestablishing tumor immunity. A prior clinical study showed CD protein expression in resected high grade glioma tumors after intravenous (IV) Toca 511 (1Cloughesy T, Walbert T, Bota D, et al. Neuro Oncol 2016; 18(suppl 6):vi17). In animal models of metastatic colorectal cancer, IV Toca 511 infected metastases; subsequent 5-FC treatment resulted in decreased tumor size, improved survival, and durable antitumor immunity (2Yagiz K, Rodriguez-Aguirre ME, Espinoza FL, et al. Molecular Therapy: Oncolytics. 2018; 8:14-26). Methods: Toca 6 is a Phase 1b, multicenter, open-label study (NCT02576665) investigating changes in immune activity after treatment with Toca 511 & Toca FC in patients with advanced solid tumors or lymphoma. Toca 511 is injected IV daily for 3 days, then intratumorally following biopsy or, for patients with brain metastases, into resection cavity walls following resection. Oral Toca FC is started ~4 weeks later and repeated every 4-6 weeks. Changes from baseline in intratumoral immune activity (infiltrating T-cell subpopulations, B cells, monocytes) at 4 weeks after start of Toca FC are assessed. Peripheral blood is analyzed for effector, memory, Treg, and myeloid lineage cells. Viral RNA, DNA, and CD protein expression in tumor after IV Toca 511 are measured. Safety and efficacy are assessed. Approximately 30 patients will be enrolled at 4 sites in the United States. Enrollment progress by tumor type will be provided at the time of the meeting. Clinical trial information: NCT02576665.
The Rekindle study: An Australian randomised phase II study assessing feasibility and promise of an online intervention to promote sexual wellbeing for both cancer survivors and their partners.
Authors: Catalina Rosario Lawsin, Kevin McGeechan, Phyllis Butow, Ilona Juraskova, Kim Hobbs, Frances M. Boyle, Judy Kay, Annie Miller, Haryana M. Dhillon
Journal: Journal of Clinical Oncology (2016)

TPS10145 Background: Many people diagnosed with cancer experience changes in their sexual function due to the disease and/or side effects of treatment. These common changes persist after treatment and may worsens over time. Changes to sexuality can lead to psychological distress for both survivors and their partners, impacting long-term quality of life. We developed Rekindle as a web-based psycho-educational intervention aimed at providing accessible, private and tailored psychosexual support to all cancer survivors and their partners, independently or as a dyad. Methods: The Rekindle study is a three-armed phase II randomized control trial conducted over six months. Treatment arms are: Rekindle, Rekindle Plus (self-led plus 3 navigational support calls) and Waitlist Control. The Rekindle intervention incorporates evidence-based strategies in seven modules to empower users to manage sexual changes. Content is delivered via the internet as written information, video testimonials, tutorials, and interactive exercises. Five of the modules are tailored into two layered; the first provides basic psycho-education, the second focuses on skills to address sexual concerns. Rekindle is tailored according to gender, patient or partner, single or partnered, and sexual preference, requiring a total of 12 versions. The Rekindle plus group complete the online intervention with 3 navigational support calls. The Waitlist Control group are provided written information via the internet during the first 10 weeks and then given access to their tailored version of Rekindle. The primary outcome is the percentage of prescribed modules users complete. Secondary outcomes are: i) change in sexual satisfaction as measured by the PROMIS sexual satisfaction scale; ii) retention in the program across groups. It is hypothesized that users randomised to Rekindle Plus will demonstrate the greatest retention and completion rates. 120 adult cancer survivors who completed primary cancer treatment 6-months prior to enrolment and/or their partners, who identified at least one psychosexual unmet need, are being recruited. Clinical trial information: ACTRN12614001245684.
Impact of viral infection on effectiveness of antitumor treatment for laryngeal cancer.
Authors: Tatiana Zykova, Oleg I. Kit, Liubov Yu Vladimirova, Ludmila A. Ryadinskaya, Elena A. Shevyakova, Olga A. Bogomolova, Marina Engibaryan, Natalya A Abramova, Anna E Storozhakova, Irina L. Popova, Natalya Mikhailovna Tikhanovskaya, Kristina A. Novoselova, Aza A. Lyanova, Yulia V. Ulianova
Journal: Journal of Clinical Oncology (2018)

e18098 Background: The impact of viral infections of tumor tissues on the effectiveness of antitumor treatment in patients with laryngeal cancer is poorly studied. Methods: Tumor tissues of 26 patients with histologically confirmed squamous cell carcinoma of the larynx (SCCL) were studied. All patients received neoadjuvant chemotherapy (CT) prior to laryngectomy: 12 pts - cetuximab+cisplatin+5-fluorouracil, 14 pts - same regimen without cetuximab. Fibrolaringoscopy was used to assess the CT results. DNAs of herpes simplex virus type 1,2 (HSV1,2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes virus type 6 (HHV6) and human papillomavirus (HPV) in tumor tissues were determined by PCR. The results were evaluated in dependence on tumor response, monoinfection or mixed infection and the CT regimen. Results: All patients with SCCL were men aged 55-68 years; stage I - 1 (4%), II – 1 (4%), III – 22 (84%), IV – 2 (8%); G1 in 10 (38%), G2 - 14 (54%), G3 - 2 (8%) pts. 96% were infected: herpes viruses in 92%, and HPV – in 4%. Pts were divided into two groups: with monoinfection – 16 (61.5%), with mixed infection – 9 (34.6%). Tumor stabilization (S) or partial regression (PR) was observed in 15 of 16 pts (94%) with monoinfection and in 4 of 9 pts (44%) with mixed infection (p = 0.01). Tumor response in pts with monoinfection: 10 of 12 (83%) with cetuximab and 5 of 14 (36%) without cetuximab (p = 0.02); in pts with mixed infection: 10 of 12 (83%) and 9 of 14 (64%), respectively (p-0.39). CR was observed in 1 patient without infections. Conclusions: The presence of monoinfection or mixed infection was found in 96% of the tumor tissue samples. The response rate depended on themono-or mixed infection type and the CT regimen.
Pharmacokinetics/pharmacodynamics (PK/PD) of ivosidenib in patients with IDH1-mutant advanced solid tumors from a phase 1 study.
Authors: Bin Fan, Ingo K. Mellinghoff, Patrick Y. Wen, Shuchi Sumant Pandya, Liewen Jiang, Guowen Liu, Tara Nimkar, Hua Yang, David Dai
Journal: Journal of Clinical Oncology (2018)

2577 Background: Mutant isocitrate dehydrogenase 1 (mIDH1) produces the oncometabolite D-2-hydroxyglutarate (2-HG). Ivosidenib (IVO; AG-120) is a targeted mIDH1 inhibitor under evaluation in an ongoing phase 1 study (NCT02073994) in mIDH1 advanced solid tumors including cholangiocarcinoma (CC), chondrosarcoma (CS), and glioma. We explored the PK profile of IVO, the relationship between IVO exposure and 2-HG inhibition, and the effect of intrinsic/extrinsic patient factors on IVO exposure. Methods: IVO was administered orally once (QD) or twice (BID) daily in continuous 28-day cycles. As of May 12, 2017, 168 patients (pts) had received IVO 100 mg BID to 1200 mg QD in dose escalation (8 dose levels, n = 60) and 500 mg QD in expansion (n = 108). IVO was assessed in plasma and 2-HG in plasma and tumor biopsies using LC-MS/MS assays. Results: After single and multiple doses, IVO showed good oral exposure, was rapidly absorbed, and plasma levels declined bi-exponentially after peaking, with a mean terminal half-life of 40–102 h after a single dose. IVO exposure and half-life were lower in pts with glioma than with CC/CS. IVO exposure increased less than dose proportionally. Steady state (SS) was reached within 14 days, with moderate accumulation (1.5- to 1.7-fold for AUC at 500 mg QD) across all tumors. No intrinsic patient factors were identified that affected IVO exposure. Mild/moderate renal impairment, mild hepatic impairment, and concomitant administration of weak CYP3A4 inhibitors/inducers had no effect on IVO clearance at SS. After multiple doses in pts with CC/CS, plasma 2-HG was reduced by up to 98% to levels seen in healthy subjects. Maximal plasma 2-HG reduction occurred at 500 mg QD in most pts, with no additional inhibition at higher doses. Tumor 2-HG showed a substantial reduction and positive correlation with plasma 2-HG. There was no significant pretreatment elevation of plasma 2-HG in glioma pts. Conclusions: IVO demonstrated good oral exposure and a long half-life, enabling oral QD dosing, and robust, persistent 2-HG inhibition in pts with mIDH1 CC/CS. IVO 500 mg QD is appropriate for these pts irrespective of intrinsic patient factors or concomitant weak CYP3A4 inhibitors/inducers. Clinical trial information: NCT02073994.
Should combination chemotherapy be used in all advanced gastric cancer patients?
Authors: Mi Sun Ahn, Yong Won Choi, Hyun Woo Lee, Seok Yun Kang, Jin-Hyuk Choi
Journal: Journal of Clinical Oncology (2018)

e16081 Background: . Although combination chemotherapy (CC) is generally recommended in advanced gastric cancer (AGC), the results of randomized trials are conflicting. We compared the outcome between CC and single-agent chemotherapy (SC) for AGC patients (pts) in real-world practice. Methods: A retrospective review was conducted on 705 pts who received palliative chemotherapy for primary metastatic (n = 395) or recurrent (n = 310) gastric cancer. We analyzed overall survival (OS) and clinicopathological characteristics affecting outcomes. Results: While CC was performed in 535 (75.9%) pts, SC was more frequently performed in old age (≥70) (58.3%) and ECOG PS 2/3 (65.4%) pts (p < 0.0001, both). The median follow-up duration was 76 months (36-163 months) for the survivors. The median OS of pts who received CC was significantly longer than that of pts who received SC (11 vs. 8 months, p < 0.0001). Although pts with CC showed better OS in the majority of subgroups, no difference in OS between CC and SC was observed in pts with old age (p = 0.675), ECOG PS 2/3 (p = 0.648), recurrent disease (p = 0.083), signet ring cell (p = 0.488), and palliative resection (p = 0.557), with a significant interaction between age and regimen (CC vs. SC) (p = 0.013). Multivariate analysis revealed that palliative resection and ≥2nd line therapy were independently associated with favorable OS (p < 0.0001, both), whereas ECOG PS 2/3 (p = 0.003), signet ring cell (p < 0.0001), and peritoneal metastasis (p = 0.014) were independent prognostic factors of poor OS. Conclusions: Although CC is the standard of care in AGC, SC can be considered as a reasonable option in certain subgroups, especially elderly pts.
TCT-579 Evaluation of the diagnostic performance of the quantitative flow ratio (QFR) according to the inter-individual variations in the adenosine response during fractional flow reserve (FFR) measurement.
Authors: Hernan Mejia-Renteria, Francesco Lauri, Fernando Macaya, Catherine Liontou, Joo Myung Lee, Nina van der Hoeven, Guus de Waard, Nieves Gonzalo, Pilar Jimenez-Quevedo, Luis Nombela-Franco, Ivan Nuñez-Gil, Pablo Salinas, Maria Del Trigo, None Tania Rodriguez Gabella, Niels van Royen, Paul Knaapen, Bon-Kwon Koo, Carlos Macaya, Antonio Fernandez-Ortiz, Javier Escaned
Journal: Journal of the American College of Cardiology (2018)
Phase Ib study of avelumab plus carboplatin in patients with metastatic castration resistant prostate cancer progressing after one line of chemotherapy and one novel androgen receptor axis inhibitor.
Authors: Alejo Rodriguez Vida, Alvaro Taus, Barbara Pons, Laia Cano, Susana Galtes, Sonia Macia, Joan Albanell, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2018)

TPS5089 Background: The management of metastatic castration resistant prostate cancer (mCRPC) has been revolutionized with the approval of several agents improving overall survival. However, despite an initial response, most patients will experience disease progression. New studies assessing new agents are still needed. Recently, several immune check-point inhibitors targeting the PD-1 pathway have been approved for the treatment of several solid tumors. However, their use in mCRPC is still at a very early phase of development. The purpose of this study is to test the safety and efficacy of combining carboplatin with avelumab in pretreated mCRPC patients. Genomic aberrations are frequent in CRPC, especially in advanced cases. By selecting pre-treated patients, we will enrich the amount of genetic aberrations (like high mutational burden or DDR mutations) potentially increasing the likelihood of response to avelumab. Cytotoxic chemotherapy like carboplatin has been shown to induce immunogenic tumor cell death, tumor-antigens release and stimulation of the immune system. It has been hypothesized that this “autovaccination” could be enhanced with the addition of immunotherapy such as avelumab. Methods: This is a phase Ib, open-label, single-arm study in patients with mCRPC progressing on at least 1 line of chemotherapy and 1 line of novel androgen receptor axis inhibitors. Inclusion criteria include performance status 0-1 and adequate organ function. Patients will receive 2 cycles of carboplatin AUC5 monotherapy followed by 2 cycles of carboplatin AUC5 plus avelumab 10mg/kg. Maintenance avelumab will continue for up to 2 years. This trial will have 2 stages. In the Safety phase (6 patients) the safety of combining both agents will be analyzed (primary endpoint). If safety is confirmed, an Expansion phase (20 patients) will assess the efficacy of the combination in terms of PSA and radiographic assessment as per PCWG3 (secondary endpoints). As exploratory endpoint, potential immunologic and genomic predictive biomarkers will be analyzed. The trial is open, and enrollment is ongoing. Clinical trial information: 2017-004552-39.
Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection
Authors: Anthony W.H. Chan, Jianhong Zhong, Sarah Berhane, Hidenori Toyoda, Alessandro Cucchetti, KeQing Shi, Toshifumi Tada, Charing C.N. Chong, Bang-De Xiang, Le-Qun Li, Paul B.S. Lai, Vincenzo Mazzaferro, Marta García-Fiñana, Masatoshi Kudo, Takashi Kumada, Sasan Roayaie, Philip J. Johnson
Journal: Journal of Hepatology (2018)

Resection is the most widely used potentially curative treatment for patients with early hepatocellular carcinoma (HCC). However, recurrence within 2 years occurs in 30-50% of patients, being the major cause of mortality. Herein, we describe 2 models, both based on widely available clinical data, which permit risk of early recurrence to be assessed before and after resection.A total of 3,903 patients undergoing surgical resection with curative intent were recruited from 6 different centres. We built 2 models for early recurrence, 1 using preoperative and 1 using pre and post-operative data, which were internally validated in the Hong Kong cohort. The models were then externally validated in European, Chinese and US cohorts. We developed 2 online calculators to permit easy clinical application.Multivariable analysis identified male gender, large tumour size, multinodular tumour, high albumin-bilirubin (ALBI) grade and high serum alpha-fetoprotein as the key parameters related to early recurrence. Using these variables, a preoperative model (ERASL-pre) gave 3 risk strata for recurrence-free survival (RFS) in the entire cohort - low risk: 2-year RFS 64.8%, intermediate risk: 2-year RFS 42.5% and high risk: 2-year RFS 20.7%. Median survival in each stratum was similar between centres and the discrimination between the 3 strata was enhanced in the post-operative model (ERASL-post) which included 'microvascular invasion'.Statistical models that can predict the risk of early HCC recurrence after resection have been developed, extensively validated and shown to be applicable in the international setting. Such models will be valuable in guiding surveillance follow-up and in the design of post-resection adjuvant therapy trials.The most effective treatment of hepatocellular carcinoma is surgical removal of the tumour but there is often recurrence. In this large international study, we develop a statistical method that allows clinicians to estimate the risk of recurrence in an individual patient. This facility enhances communication with the patient about the likely success of the treatment and will help in designing clinical trials that aim to find drugs that decrease the risk of recurrence.