tbuckley/cabot-search huggingface dataset:
Abstract 13879: Clinical Features and Prognosis of Patients With Left Ventricular Noncompaction Cardiomyopathy: A Comparison Between Infantile and Juvenile Types
Authors: Asami Takasaki, Sayaka Ozawa, Nariaki Miyao, Hideyuki Nakaoka, Keijiro Ibuki, Keiichi Hirono, Naoki Yoshimura, Fukiko Ichida
Journal: Circulation (2015)

Introduction: Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by a left ventricle with a prominent trabecular meshwork. Long-term prognosis of LVNC has not been elucidated yet. Purpose: The aim of this study is to clarify the difference between infantile and juvenile cases and identify the risk factor of poor prognosis of LVNC in the largest series to date. Methods: Based on nationwide surveys of LVNC in Japanese children, we compared the clinical features and anatomical properties of infantile cases of LVNC (&lt; 2 years: 85 cases) with that of juvenile cases (2-15 years: 73 cases). In addition to the standard noncompacted to compacted layer (N/C) ratio, we developed an echocardiographic criteria which represents an average of N/C ratios in five wall segments to estimate the severity of LVNC. Results: The duration of follow-up ranged from 15 days to 22 years (median 5 years). Although most patients in the infantile group had clinical signs of heart failure at initial presentation (70.1%), the majority of juvenile cases were asymptomatic and identified when screened for cardiac abnormalities, such as ECG screening (55.8%). WPW syndrome was higher in both groups (infantile group: 9.7%, juvenile group: 10.0%), the incidence of LBBB and VT was lower than those reported in adults. On echocardiography, the maximum N/C ratio was observed at the apex in both groups. Neither noncompaction score nor N/C score was significantly different between groups. Left ventricular ejection fraction (LVEF) at initial presentation was significantly lower in the infantile group than in the juvenile group. Although survival analysis showed poor prognosis in the infantile group, the significant risk factor was LVEF below 50% (p = 0.0004, hazard ratio = 9.0), rather than age of onset. Conclusions: LVNC in both infantile and juvenile groups showed poor prognosis when correlated with depressed LVEF at initial presentation.
Process improvement and cost savings in cancer care through the utilization of technology in tumor boards.
Authors: Lijo Simpson, Anju Mathew
Journal: Journal of Clinical Oncology (2018)

e18779 Background: Multidisciplinary tumor conferences provide an opportunity to enhance patient care. The engagement of multiple disciplines is thought to improve outcomes for cancer patients. To attain CoC accreditation a cancer program has to collect metrics during Tumor Boards(TB) that demonstrate high quality cancer care including Staging, Compliance to National Guidelines, Prospective Case and Clinical Trial discussion. Tumor Boards consume significant resources requiring on average 10 hours of administrative time per TB conducted. With 85% of cancer patients receiving care in community cancer centers, finding cost effective mechanisms for multidisciplinary TBs is important. Methods: Analysis indicates the annual hospital cost of running a weekly TB is $91000. This includes hourly salaries of the coordinators, room and meal costs. This does not include the physicians’ time. To decrease resource utilization and increase the quality of discussions, we implemented a TB Platform, OncoLens. This is a cloud based SaaS platform that manages all aspects of running TB’s and subsequently reporting to the CoC and NAPBC. The platform also automatically screens patients for available clinical trials. Results: 790 cases were discussed in the past one year. This is a 30% increase in cases discussed. The highest number of cases discussed are Breast Cancer (358, 45%), Lung Cancer (87, 11%) and Gynecologic malignancies (134, 17%). Clinical trials were discussed in 222 cases (28%). 76% of cases were prospective while staging was discussed in 75% of cases. Direct cost savings achieved was 40,000$ in Year 1. Staff time to conduct TBs was reduced to less than two hours per conference. Conclusions: The following benefits were observed in a center running six TBs a month by implementing an electronic TB Platform. 1. Increase the number of cases discussed by 30%. 2. Reduced cost and work load for the cancer center. 3. It is possible to standardize TB discussions across different health care systems in the country. The data required by the CoC for accreditation can be collected by an electronic platform. 4. Automatic software driven screening of clinical trials can drive an increase in discussion of options for the patient.
Phase III (IMROZ) study design: Isatuximab plus bortezomib (V), lenalidomide (R), and dexamethasone (d) vs VRd in transplant-ineligible patients (pts) with newly diagnosed multiple myeloma (NDMM).
Authors: Robert Z. Orlowski, Hartmut Goldschmidt, Michele Cavo, Thomas G. Martin, Gautier Paux, Corina Oprea, Thierry Facon
Journal: Journal of Clinical Oncology (2018)

TPS8055 Background: Pts with transplant-ineligible NDMM require therapies which prolong survival and improve quality of life. The combination of VRd significantly improves progression-free (PFS) and overall survival compared with Rd in NDMM, and has an acceptable safety profile. Combining VRd with a monoclonal antibody (mAb) may further improve efficacy. Isatuximab (ISA) is an anti-CD38 mAb that demonstrates antitumor and immunomodulatory activities with strong potentiation when combined with V and R in MM xenograft models. Here we describe a Phase III, randomized, open-label, multicenter study (NCT03319667; IMROZ), evaluating clinical benefit of ISA plus VRd vs VRd in pts with transplant-ineligible NDMM. Methods: Approximately 440 adult pts with symptomatic MM (International Myeloma Working Group [IMWG] criteria) will be randomly assigned, according to Revised International Staging System criteria (I or II vs III vs unknown) and age ( < 70 vs ≥70 years), in a 3:2 ratio to ISA (10 mg/kg on Days 1, 8, 15, 22, 29 in Cycle 1; every 2 weeks [Q2W] thereafter), plus V (1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29, 32), R (25 mg on Days 1–14, Days 22–35), and d (20 mg on Days 1, 2, 4, 5, 8, 9, 11, 12, 15, 22, 23, 25, 26, 29, 30, 32, 33), or VRd alone for 4 6-week cycles (induction phase). After Cycle 4, pts will receive Rd with or without ISA in 4-week cycles (R on Days 1–21; d weekly; ISA Q2W) until disease progression, unacceptable adverse events (AEs), or pt decision to discontinue (continuous phase). ISA will be reduced to monthly dosing from Cycle 18. Pts who progress on Rd can cross-over to ISA plus Rd. Primary endpoint is PFS (IMWG criteria) assessed by a blinded independent review committee, and analyzed with a 1-sided stratified log-rank test. Key secondary endpoints include rate of very good partial response or better, minimal residual disease negativity rate, and complete response rate. Safety evaluations include AEs, laboratory parameters, vital signs, and physical examination. The IMROZ study is currently enrolling pts; recruitment is planned in approximately 100 countries worldwide, including Japan and China. Study funding: Sanofi. Clinical trial information: NCT03319667.
Excision repair cross complementation group 1 (ERCC-1) gene polymorphisms and response to nivolumab in advanced non-small cell lung cancer (NSCLC).
Authors: Marco M. Aiello, Paolo Giovanni Vigneri, Paolo Bruzzi, Francesco Verderame, Sabrina Paratore, Nunzio Restuccia, Valeria Albanese, Hector J. Soto Parra
Journal: Journal of Clinical Oncology (2017)

3032 Background: Anti PD1 antibodies showed significant clinical activity in different cancer types. Recently, it was observed that cancers with higher somatic mutation burden, as tumors with genome instability due to DNA repair defects, develop more elevated anti PD1 induced neoantigen specific T cell reactivity which results into increased susceptibility to PD1 blockade. We hypothesize that NSCLC pts with single nucleotide polymorphisms (SNPs) of the ERCC-1 gene, a key enzyme of DNA nucleotide excision repair pathway, may be more responsive to PD-1 blockade due to their genetic instability. Methods: We evaluated the rs11615 and rs3212986 ERCC1 SNPs by pyrosequencing analysis on tumor DNA of stage IIIb-IV previously treated NSCLC patients receiving Nivolumab (Nivo) 3 mg/kg q2w. To be eligible for this study, pts had to have a complete record of clinical and radiological parameters. Objective tumour response was assessed according to RECIST 1.1 criteria. Results: Between Jul 2015 and Jan 2016, 45 NSCLC pts received Nivo. Pts characteristics were as follows: M/F = 37/8; median age (range) = 64 (38-80); ECOG PS, 0/1/2 = 33/9/3; Stage IIIb/IV = 8/37; sqNSCLC/non sq NSCLC = 11/34; current-former smokers/non-smokers = 40/5; EGFR status, mutant/wildtype/unknown = 4/35/6; median cycles (range) = 12 (1-28). Only two pts presented the rs11615 SNP. 16 pts were positive for the rs3212986 SNP. ORR for all pts was 26.6% (95% CI, 10 to 47). The ORR was significantly higher in NSCLC pts positive for the rs3212986 SNP than for wild-type NSCLC patients (62.5% vs. 6.9%. p = 0.0001). For all pts median PFS was 4.3 mos (95% CI, 1.2 to 7.4)and median OS not-reached. Among pts positive for the rs3212986 SNP, median PFS and OS were 8.2 mos and not-reached respectively. In contrast wild-type patients presented a median PFS of 3.1 mos (HR = 0.21 95% CI, 0.07 to 0.57; p = 0.02) and a median OS of 6.5 mos (HR = 0,403 95% CI = 0,131-1,237 p = 0.11). Multivariate analyses confirmed the effect of rs3212986 SNP after adjustment for age, PS, sex and disease stage for PFS. Conclusions: This study suggests that genetic instability due to tumor ERCC1 SNPs in advanced NSCLC pts may be of value to predict clinical benefit from Nivo.
Impact of exercise on psychological burden in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Emily S. Tonorezos, Jennifer Ford, Linwei Wang, Kirsten K. Ness, Yutaka Yasui, Wendy M. Leisenring, Charles A. Sklar, Leslie L. Robison, Kevin C. Oeffinger, Paul C. Nathan, Gregory T. Armstrong, Kevin R. Krull, Lee Jones
Journal: Journal of Clinical Oncology (2018)

10513 Background: Adult survivors of childhood cancer are at risk for adverse psychological outcomes. Whether exercise can attenuate this risk is unknown. Methods: Using a longitudinal design, 6199 CCSS participants (median [range] age 34 years [22-54] and median [range] age at diagnosis 10 years [0-21]) completed a baseline questionnaire assessing vigorous exercise, medical and psychological conditions. Psychological outcomes were evaluated in a subsequent questionnaire a median of 7.8 years later (range 0.1-10). Primary outcome was overall psychological burden, defined as: symptom level above the 90th percentile of population norms on the Brief Symptom Inventory-18 for depression, anxiety, or somatization ; cancer-related pain; cognitive impairment; or poor quality of life. Log-binomial regression estimated associations between exercise [total metabolic equivalent-hrs.wk-1 (MET-hrs.wk-1)] and these outcomes adjusting for cancer diagnosis/treatment, demographics, and baseline medical/psychological illness. Results: The prevalence of overall psychological burden at follow-up was 71.3%. The prevalence of depression was 11.4%, anxiety 7.4%, and somatization 13.9%. Among those not engaged in vigorous exercise, the prevalence of overall psychological burden was 75.9%, compared to 68.6% in those who exercised ≥3 MET-hrs.wk-1 (p < 0.001). Compared to 0 MET-hrs.wk-1 of vigorous exercise, the adjusted prevalence ratio (PR) for overall psychological burden was 0.98 (95% CI, 0.95-1.01) for 3-6 MET-hrs.wk-1, 0.93 (95% CI, 0.90-0.96) for 9-12 MET-hrs.wk-1, and 0.94 (95% CI, 0.90-0.98) for 15-21 MET-hrs.wk-1. Compared to not reporting vigorous exercise, 9 to 12 MET-hrs.wk-1 was associated with an adjusted PR of 0.76 (95% CI, 0.62-0.93; p = 0.004) for depression and 0.79 (95% CI, 0.66-0.94; p = 0.003) for somatization. Vigorous exercise was associated with higher cognitive function in domains of task completion, organization, and working memory (p's < 0.05) but was not associated with cancer pain or quality of life. Conclusions: Vigorous exercise is associated with lower psychological burden and less cognitive impairment in long-term survivors of childhood cancer.
Peritoneal Surface Oncology Group International (PSOGI) multicenter study on nomograms to predict overall survival in diffuse malignant peritoneal mesothelioma.
Authors: Shigeki Kusamura, Francesco Barretta, Paul H. Sugarbaker, Edward Allen Levine, Olivier Glehen, David L. Morris, Michele De Simone, Diane Goere, Brendan J. Moran, Yutaka Yonemura, Rosalba Miceli, Dario Baratti, Marcello Deraco
Journal: Journal of Clinical Oncology (2018)

e15701 Background: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare disease whose therapy of choice is cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Literature lacks prognostic tools for DMPM. Thus we aimed to build nomograms for perioperative prediction of overall survival (OS) in patients treated with CRS +/- HIPEC. Patients and Methods: We included in the study consecutive DMPM patients from PSOGI registry. The training set comprised 541 patients from 8 centers, and the testing set, 172 patients from 22 centers. We handled missing data with multiple imputation. We build nomograms to predict pre and postoperative OS from surgery. We selected putative prognostic variables using backward selection and performed multivariable Cox models. We assessed validation and discriminative ability of the nomograms in both training and testing sets. We plotted decision curve analysis (DCA) graphs for both nomograms at all times to evaluate clinical usefulness. Results: In the training set (median follow-up 68 months; interquartile range [IQR] 30-119 months), 288 deaths were recorded. 1, 3, and 5-year OS rates were 77.3%, 55.4%, and 44.5%, respectively. In the testing set (median follow-up 48 months; IQR 23-84 months), 96 deaths were recorded. 1, 3, and 5-year OS rates were, 73.9%, 50.6%, and 33.2%, respectively. Significant OS predictors in the preoperative model were age, histological subtype, and pre-CRS peritoneal cancer index. Significant OS predictors in the postoperative nomogram were age, histological subtype, residual disease, and severe morbidity. Both nomogram models were well calibrated, in both sets at all times. Harrell C indexes for preoperative nomogram were 0.69 (training set) and 0.73 (testing set). The same indexes for postoperative nomogram were 0.73 (training set) and 0.71 (testing set). DCA results show better clinical usefulness of the nomograms in preclinical evaluations and shorter times. Conclusions: The nomograms allow the prediction of OS, could assist perioperative decision-making, and allow patient stratification in future clinical trials.
PRKDC: A new candidate for checkpoint blockade immunotherapy?
Authors: Ming Huang Chen, Kien Thiam Tan, Jen Hao Cheng, Wen-Liang Fang, Yi Chen Yeh, Chun-Nan Yeh, Yu Chan Chang, Shu-Jen Chen, Michael Hsiao, Yee Chao
Journal: Journal of Clinical Oncology (2017)

3022 Background: Immunologic checkpoint blockade with antibodies that target CTLA-4 or PD-1/PD-L1 have demonstrated promise in a variety of malignancies. However, the treatment response rate of these immunologic checkpoint blockades remains low. Identifying predictive biomarkers to assist patient selection for immunotherapy have become a priority in both clinical and research settings. Methods: Mutations in patients who responded to immunotherapy were identified by Next-Generation Sequencing (NGS). Relationship between mutation of PRKDC, mutation load and known immune biomarkers were analyzed using datasets from The Cancer Genome Atlas (TCGA). Following up, the PRKDC protein expression was evaluated in 439 gastric cancer patients by immunohistochemical staining and their MSI statuses were evaluated by PCR. Results: We first identified PRKDC mutations in two responders to immune checkpoint therapy (1 HCC, 1 gastric cancer). From published literature, we further discovered that 66.7% (2/3) of lung cancer patients and 63.6% (7/11) of melanoma patients whose tumor harbored PRKDC mutation and responded to immunotherapy. Most of these mutations detected in responders were either truncating or located in functional domains. Further analysis showed that PRKDC mutation is significantly associated with high mutation load in cervical cancer, colon adenocarcinoma, head and neck squamous cell carcinoma, lung adenocarcinoma, gastric adenocarcinoma and endometrial cancer ( p= 0.008, p= 0.0108, p= 0.0166, p= 0.0183, p&lt; 0.001 and p&lt; 0.001, respectively). Interestingly, gastric cancer patients harboring PRKDC mutations or with MSI-H demonstrated significantly higher gene expression in PDL1, TIM3, LAG3, IFNG, CXCL9, CXCL10, GZMA and PRF1, compared to MSS patients ( p= 0.0016, p= 0.0142, p= 0.0017, p= 0.0034, p= 0.0118, p&lt; 0.0001, p= 0.0001, p&lt; 0.0102, respectively). Finally, we discovered low expression of PRKDC was a poor prognostic factor and significantly correlated with MSI-H in gastric cancers. Conclusions: PRKDC may be a potential biomarker that can identify responders to immune checkpoint inhibition.
Phase I expansion cohort to evaluate bevacizumab, sorafenib, and low-dose cyclophosphamide in children and young adults with refractory or recurrent solid tumors.
Authors: Sara Michele Federico, Mary B McCarville, Clinton F. Stewart, Shenghua Mao, Jianrong Wu, Andrew M. Davidoff, Wayne Lee Furman, Victor M. Santana, Alberto S. Pappo, Fariba Navid
Journal: Journal of Clinical Oncology (2016)

10519 Background: Angiogenesis is required for tumor growth and metastasis. Both VEGF and PDGFR are key regulators of tumor vasculature. In preclinical models, dual inhibition of VEGF and PDGFR signaling result in more effective tumor suppression and improved survival. We report the results of an expansion cohort of a phase I study targeting angiogenesis with sorafenib, bevacizumab and low-dose cyclophosphamide in children and young adults with solid tumors. Methods: The treatment doses and schedule of the combined therapy were derived from results of a previously reported dose-escalation phase I study (Navid F et al. Clin Cancer Res 2013). Four cohorts of 6 patients with refractory or recurrent solid tumors were enrolled and received bevacizumab (15mg/kg IV, day 1), sorafenib (90mg/m2 po BID, days 1-21) and low-dose cyclophosphamide (50mg/m2 po daily, days 1-21). Each course of therapy lasted 21 days. Serial bevacizumab pharmacokinetic (PK) studies were performed during course 1. Toxicity was assessed using CTCAE 3.0. Response was assessed using RECIST1.1. Results: Twenty-four patients (15 males; median age 14.5 yrs; range 1.1-22.4 yr) received a median of 6 courses (range 1-18) of therapy. Twelve patients had a bone or soft tissue sarcoma and 12 patients had a non-sarcoma solid tumor. The most common grade 3/4 non-hematologic toxicities were hypertension (4), hand/foot rash (3) and elevated lipase (3). The most common grade 3/4 hematologic toxicities were neutropenia (7) and lymphopenia (17). Three patients (2 synovial sarcoma, 1 rhabdoid tumor) achieved a partial response and 18 had disease stabilization. The progression-free survival at 3 and 6 months were 78.1% (95% CI 60.6-95.6%) and 54% (95% CI 30.2-78.2%). Bevacizumab PK studies were performed in 15 patients and the median (range) clearance, Cmax, Tmax and AUC were 4.4mL/day/kg (2.8-6.0), 331µg/mL (206-441), 1.9hrs (1.6-4.6) and 3345µg/mL*day (2566-5297) respectively. Conclusions: This treatment regimen is well tolerated and demonstrated promising activity in a variety of childhood solid tumors. Additional studies are warranted. Clinical trial information: NCT00665990.
Prognostic impact of <i>PD-1</i>, <i>PD-L1,</i> and <i>CD8</i> genes expression in peripheral blood in gastric cancer.
Authors: Shuhei Ito, Takaaki Masuda, Takeo Fukagawa, Yuta Kouyama, Hiroaki Wakiyama, Yukihiro Yoshikawa, Miwa Noda, Shinya Kidogami, Qingjiang Hu, Kuniaki Sato, Sho Nambara, Tomoko Saito, Shotaro Sakimura, Naoki Hayashi, Yousuke Kuroda, Hidetoshi Eguchi, Mitsuru Sasako, Koshi Mimori
Journal: Journal of Clinical Oncology (2017)

11531 Background: Programmed death 1 (PD-1)/PD-1 ligand (PD-L1) blocking agents to gastric cancer (GC) in the clinical setting show significant therapeutic promise. However, since these agents are enormously expensive and potentially toxic, it is crucial to identify predictive biomarkers for detecting the best candidate who would benefit from these agents by less invasive and simpler method, such as liquid biopsy. Methods: Expression levels of genes coding for PD-1, PD-L1 and CD8 (CD8+ T cells are closely associated with cellular immune responses to tumors) were assessed in peripheral blood (PB) samples using quantitative RT-PCR. Samples were obtained from 407 GC patients (392 patients with neoadjuvant chemotherapy [NAC] and 15 patients without NAC) before surgery and 23 PB from normal controls (NC). Flow cytometric analysis was performed to identify PD-1-expressed cells in PB mononuclear cells. Results: PD-1, PD-L1 and CD8 mRNA levels of GC patients were significantly higher than those of NC: 4.2-, 3.0- and 6.1-fold increases, respectively (P &lt; 0.0001, P = 0.0001 and P &lt; 0.0001). PD-1 mRNA levels were significantly lower in GC patients with NAC than in GC patients without NAC (P &lt; 0.01). GC patients with low PD-1, high PD-L1 and low CD8 mRNA levels had significantly poorer overall survival (OS) than those with high PD-1, low PD-L1 and high CD8 mRNA levels, respectively (P &lt; 0.05, P &lt; 0.05 and P &lt; 0.05). Multivariate analysis showed that PD-1 low/ PD-L1 high mRNA levels was independent risk factors for OS (OR 2.15, 95%CI 1.29-3.45, P &lt; 0.01). Flow cytometric analysis demonstrated the proportion of CD3 (T cell marker)-positive cells in the PD-1-positive fraction were 95.4 ± 6.9% in GC patients. Thus, most PD-1 protein expression occurred on T cells. Taken together, PD-1, PD-L1 and CD8 mRNAs in PB were overexpressed in GC patients, and PD-1 mRNA levels which was mostly expressed on T cells in protein levels in PB were decreased in GC patients with NAC. Furthermore, relative levels of PD-1, PD-L1 and CD8 were associated with prognosis, respectively. Conclusions: Preoperative PD-1, PD-L1 and CD8 mRNA levels in PB may reflect antitumor immune response, and PD-1 low/ PD-L1 high mRNA levels in PB are markers of poor prognosis in GC patients.