tbuckley/cabot-search huggingface dataset:
Toxicities associated with checkpoint inhibitor immunotherapy: The Karmanos Cancer Center experience.
Authors: Misako Nagasaka, Roba S Alhasan, Marcus Crosby, Nithin Thummala, Seongho Kim, Judith Abrams, Ammar Sukari
Journal: Journal of Clinical Oncology (2017)

e14575 Background: PD-1 inhibitors work by re-instating the natural anti-cancer immune-mediated cytotoxicity. Although this new class of therapy offers hope for many advanced stage cancer patients (pts), data on pts who are more likely to experience adverse events (AE) are not available. Methods: Data from pts who received at least one dose of PD-1 inhibitors before August 31, 2016, were captured from our institution’s pharmacy database. AE of anemia, neutropenia, thrombocytopenia, acute kidney injury, hypothyroidism, transaminitis, pneumonitis, colitis and fatigue were recorded and graded based on CTCAEv4. Baseline pt characteristics were statistically compared between subjects who received PD-1 inhibitors on a clinical trial vs as part of standard of care (on vs. off-study) by Fisher’s exact test for categorical variables and Kruskal-Wallis test for continuous variables. Univariable and multivariable logistic regression models were fit to assess associations between toxicities (Grade0-1 vs. Grade2+) and predictors (age, agent, primary tumor, and trial status). Results: 231 pts received at least one dose of PD-1 inhibitors prior to data cut-off. Median age was 65 (24-92) off trial (n = 125) and 59. 5 (25-79) on trial (n = 106). There were 117 (51%) non-small cell lung cancer (NSCLC), 41 (18%) renal cell carcinoma (RCC) and 73 (32%) others. 24 (10%) melanoma, 18 (8%) Hodgkin’s lymphoma (HL), 9 (4%) head and neck squamous cell carcinoma (HNSCC), 8 (4%) small cell lung cancer (SCLC) were included in others. 129 (56%) had nivolumab alone, 50 (22%) had pembrolizumab alone and the rest 52 (23%) received combination treatment. Pts participating in a clinical trial had higher odds to experience grade 2 or more pneumonitis than those not on a trial (unadjusted p = 0.038). On trial pts had lower odds to experience grade 2 or more fatigue than those receiving the agent as standard of care (unadjusted p = 0.026) which remained significant after adjusting age, agent (single agent vs combination) and primary tumor (adjusted p = 0.004). Conclusions: In our observation, pneumonitis was seen more on clinical trials whereas fatigue was seen less.
CT-guided percutaneous radiofrequency ablation in the treatment of stage I thymoma.
Authors: Jun Dong, Xiaojing Geng, Wang Li, Bei Zhang, Liangping Xia, Pili Hu, Roujun Peng, Peihong Wu
Journal: Journal of Clinical Oncology (2017)

e18287 Background: Thymoma is an uncommon tumor originating from the epithelial cells of the thymic epithelium. It is commonly associated with myasthenia gravis. Though surgical resection might provide the hope of curing thymoma, potential risks of invasive trauma and post operation complications still exists. Video-assisted thoracoscopic surgery (VATS) has many advantages over traditional surgery including minor trauma. However, surgeons operating the equipment to perform VATS need to be highly specifically trained. Although CT-guided percutaneous radiofrequency ablation (RFA) has emerged as a minimally invasive and curative treatment in other tumors, it has never been used in the treatment of stage I thymoma. Methods: The current study enrolled 13 patients with stage I thymomas whom refused open surgery or VATS. As a result, all patients received first-line CT-guided percutaneous RFA as treatment. The procedure was clearly described and displayed for clinical promoting. Results: The feasibility and treatment effectiveness were also recorded. The median time of ablation was 15 mins (range, 10 - 20 mins). Minimum blood loss was associated with the puncture. All lesions were completely ablated (13/13, 100%). Only one patient out of thirteen had thymoma recurrence at 35.5 months after initial ablation treatment (1/13, 7.7%) at follow-up period (median 80.5 months, range, 64.6-116.9 months). There was no procedure-related death after RFA treatment. Myasthenia gravis was cured in most patients (10/13,76.9%), alleviated in 3 patients (23.1%). The most common complications recorded were fever (13/13, 100%), incisional pain (13/13, 100%), nausea (38.5%), pleural effusion (69.2%), pneumothorax (69.2%) and hemoptysis (84.6%). Conclusions: It is clinically applicable for CT-guided percutaneous RFA to be considered as a safe and effective treatment in stage I thymoma.
NIVES study: A phase II trial of nivolumab (NIVO) plus stereotactic body radiotherapy (SBRT) in II and III line of patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Cristina Masini, Cinzia Iotti, Patrizia Ciammella, Roberta Gnoni, Annalisa Berselli, Maria Giuseppa Vitale, Ugo De Giorgi, Claudia Mucciarini, Sebastiano Buti, Giuseppe Procopio, Roberto Iacovelli, Giorgio V. Scagliotti, Sergio Bracarda, Orazio Caffo, Franco Morelli, Carmelo Bengala, Franco Nole, Susanne Baier, Stefano Panni, Carmine Pinto
Journal: Journal of Clinical Oncology (2018)

TPS4602 Background: Despite recent advances in drug therapy, pts with mRCC have about a 10% 5-year survival rate. Several preclinical studies have documented an increase in peripheral antitumour immunity following radiation, a phenomenon known as the abscopal effect. NIVO is an anti-programmed cell death-1 (PD-1) monoclonal antibody that blocks tumour growth in different ways by targeting certain cells. It might work even better when combined with SBRT. The irradiated tumour cell death can enhance antitumor immunity by inducing antigen expression on tumour cells and activating lymphocytes. The aim of the study is to evaluate whether the antitumour immunity of NIVO can be enhanced by SBRT. Methods: This is an ongoing phase II, single arm, multicentre study in pts with mRCC with progression disease after ≤ 2 prior anti-angiogenic therapies and with 2 or more measurable non-brain metastatic sites, at least one of which potentially suitable for treatment with SBRT. All pts will receive hypofractionated radiation at a lesion at a dose and schedule of 10 Gy/3 fractions respectively after 7 days from the first infusion of NIVO. NIVO will be given as flat dose of 240 mg in intravenous infusion beginning on day 1 every 14 days for 6 months, then switch to 480 mg q4-weekly in responding (CR, PR, SD) pts until PD or unacceptable toxicity. The primary objective is to evaluate the activity of this combination in terms of Objective Response Rate (ORR), the best response recorded on the ITT population according to RECIST v1.1. Our hypothesis is that treatment with NIVO plus SBRT compared to NIVO monotherapy can increase the ORR from 25% to 40%. Secondary endpoints are progression free survival (PFS), overall survival (OS), ORR of irradiated and non-irradiated metastases, duration of response and safety profile. An Exploratory Project also identifies molecular basis of synergistic effect of SBRT and immunotherapy, potential mechanisms of resistance to checkpoint inhibitors. Twenty of the planned 68 pts were enrolled from July 2017 to January 2018. Study duration will be 12 months for the accrual and 36 months for the follow-up. Clinical trial information: EudraCT Num 2016-003032-20. Clinical trial information: EudraCT Number 2016-003032-20.
The efficacy of adjuvant interferon, tumor vaccines and cellular immunotherapies in hepatocellular carcinoma.
Authors: Qiyun Ou, Yunfang Yu, Anlin Li, Tuping Fu, Quanlong Gao, Xiaoyun Xiao, Baoming Luo
Journal: Journal of Clinical Oncology (2018)

e16125 Background: The role of adjuvant interferon, tumor vaccines or cellular immunotherapies in patients with hepatocellular carcinoma (HCC) continues to be debated. This study aimed to assess the comparative efficacy of adjuvant interferon, tumor vaccination and cellular immunotherapy in HCC. Methods: We searched for randomized clinical trials (RCTs) investigating adjuvant interferon or vaccine or cellular immunotherapy in stage I-III HCC until February 2018. Overall survival (OS) and disease-free survival (DFS) were calculated hazard ratios (HRs) using random-effects model and in stratified defined by different immunotherapies. Quality of evidence was appraised with GRADE criteria. PROSPERO registry number is CRD42018083991. Results: 17 RCTs including a total of 1,942 patients were identified. Patients treated with immunotherapy obtained prolonged DFS (HR 0.66, 95% confidence interval [CI] 0.56 to 0.77, P < 0.0001; high certainty), and OS (HR 0.60, 95% CI 0.46 to 0.77, P < 0.0001; high certainty) compared with non-immunotherapy. In stratified analysis, compared with non-cellular immunotherapy, there was high certainty that cellular immunotherapy had prolonged DFS (HR 0.62, 95% CI 0.51 to 0.76) and OS (HR 0.59, 95% CI 0.42 to 0.83). High certainty suggested that interferon as adjuvant therapy had prolonged DFS (HR 0.77, 95% CI 0.62 to 0.95) and OS (HR 0.71, 95% CI 0.54 to 0.95) compared with non-interferon. There was low certainty of tumor vaccine as adjuvant therapy, compared with non-vaccine, resulted in prolongation of DFS (HR 0.19, 95% CI 0.05 to 0.71) and OS (HR 0.07, 95% CI 0.02 to 0.26). Contrasted with non-immunotherapy, immunotherapy had significantly benefits improved DFS after hepatic resection (HR 0.63, 95% CI 0.51 to 0.79; high certainty), but no different after radiofrequency ablation (HR 1.03, 95% CI 0.49 to 1.17; low certainty). Conclusions: This study provided an evidence that adjuvant interferon, tumor vaccine or cellular immunotherapy are associated with significantly prolonged DFS and OS in patients with stage I-III HCC, while a clear advantage of immunotherapy after radiofrequency ablation has not been established.
Activated PIK3CD drives innate B cell expansion yet limits B cell–intrinsic immune responses
Authors: Michelle N. Wray-Dutra, Fahd Al Qureshah, Genita Metzler, Mohamed Oukka, Richard G. James, David J. Rawlings
Journal: The Journal of Experimental Medicine (2018)

Activated PI3K-delta syndrome (APDS) is an immunodeficiency caused by gain-of-function mutations in PIK3CD. This disease exhibits complex immune phenotypes including increased IgM, recurrent infection, and impaired vaccine responses. To better understand the impact of B cells in this disease, we generated an inducible model of the common APDS mutation (hPIK3CD-E1021K; referred to as aPIK3CD) and intercrossed these mice with B cell-specific Cre models. Mb1-aPIK3CD mice exhibited bone marrow B lymphopenia and, conversely, expansion of the peripheral innate B1a and MZ B cell compartments. aPIK3CD B cells manifest increased pS6 and increased survival at several stages, without alterations in cycling, and baseline increases in plasma cells, natural IgM, and IgG3. Finally, Mb1-aPIK3CD mice exhibited blunted T cell-independent immune responses, and both AID- and CD21-aPIK3CD mice displayed reduced class-switched antibodies following T cell-dependent immunization. Thus, aPIK3CD alters B cell development and function and is counter-productive during immune responses, providing insight into B cell-intrinsic contributions to the APDS phenotype.
Implications of melanoma with diabetes mellitus on patient outcomes.
Authors: Nina J. Karlin, Heidi E. Kosiorek, Matthew Buras, Shailja Amin, Patricia M. Verona, Curtiss B. Cook
Journal: Journal of Clinical Oncology (2018)

e21595 Background: This study examined the impact of diabetes mellitus (DM) on survival in melanoma patients, and the impact of melanoma on glycemic control. Methods: Melanoma patients with DM (n = 56) from 2005-2016 were matched to melanoma patients without DM (n = 56) according to age, gender, and year of cancer diagnosis. Patients with melanoma in-situ were excluded. Overall survival (OS) and progression free survival (PFS) were estimated with the Kaplan-Meier method and compared by Cox regression analysis. Mixed models compared hemoglobin A1c (HbA1c) and glucose over time. Results: Mean age of the entire cohort was 77 (SD = 10) years, 99% were white, and 70% had stage I disease. No differences in age, race/ethnicity, tumor stage, or ECOG performance status were detected between patients with and without DM, although DM patients had higher body mass index (mean = 31.2 (6.3) versus 28.4 (6.8); p = 0.03). Among those with DM, the mean HbA1c during the year following cancer diagnosis was 6.7% and did not change over time (p = 0.72). Mean glucose was significantly different between DM (141 mg/dl) and non-DM (103 mg/dl) patients (p = 0.002). Neither group had a decline in glucose value during the one year following cancer diagnosis as there was no significant interaction (p = 0.82) or time effect (p = 0.99). There was a median follow-up time of 75.1 (2.0-143.9) months in living patients. Five year OS was estimated at 89% (95% CI: 80-99%) for DM patients versus 70% (95% CI: 58-85%) in non-DM patients. Hazard ratio (HR) for matched pairs was 0.42 (95% CI: 0.15-1.18; p = 0.10). Five year PFS was estimated at 89% (95% CI: 81-99%) for DM and 63% (95% CI: 51-79%) for non DM patients. HR for matched pairs was 0.29 (95% CI: 0.11-0.80; p = 0.02). Conclusions: Melanoma did not adversely impact glycemic control. DM did not adversely impact survival in patients with melanoma. Superior five year PFS in DM patients is thought provoking and warrants further study.
EGFR status evaluation by liquid biopsy during first-line therapy in patients with advanced NSCLC.
Authors: Francesca Zanelli, Maria Pagano, Candida Bonelli, Bruno Casali, Alberto Cavazza, Enrico Farnetti, Roberta Gnoni, Mario Larocca, Davide Nicoli, Carmine Pinto
Journal: Journal of Clinical Oncology (2017)

e20524 Background: over the past decade, personalized management based on the molecular features of tumours in patients with advanced non small-cell lung cancer (NSCLC) has entered routine clinical practice. The poor performance of many advanced NSCLC patients may limit invasive biopsies. The liquid biopsy is a diagnostic procedure performed on cancer-derived material obtained in blood samples. In this abstract, we will describe our experience with liquid biopsies. Methods: In the Reggio Emilia Clinical Cancer Centrefrom March 2016 to December 2016, 42 patients with advanced NSCLC were analyzed that had had or had already started first line therapy. The liquid biopsy was repeated at each imaging response evaluation by thoracic-abdominal compound tomography (CT) scan performed every 3 months. In the liquid biopsy, the mutational status of EGFR was analyzed with real time PCR (KIT cobas EGFR mutation test v2 CE-IVD Roche); in tissue, it was evaluated by pyrosequencing. Results: 21/42 liquid biopsies were EGFR-mutated (12/21 eson 19 and 9/21 eson 21). In 3/21 (14.3%) cases, the tissue biopsies showed wild type (WT) EGFR. 6 liquid biopsies were also performed at time 0 (diagnosis). All liquid biopsies of EGFR WT remained WT during treatment and imaging evaluation. The median number of liquid biopsy tests for patients was 2 (range 1-3). In 4/21 cases, T790M was performed: 3 cases in both liquid biopsies and tissue, and 1 case in tissue but not in liquid biopsy. TKi therapy was ineffective in this patient with T790M mutation detected in tissue, but not in liquid biopsy. In all patients, the disappearance of the T790M mutation during TKi therapy was related to disease progression. In 11 cases, modification of EGFR mutation status during treatment anticipated CT scan evidence of disease progression (median = three months). Conclusions: the liquid biopsy is an excellent resource. In our experience the liquid biopsy is the sensitive method of choice during treatment of advanced NSCLC patients. EGFR modification status during TKi therapy showed advanced disease progression.
Low-Molecular-Weight Cyclin E in Human Cancer: Cellular Consequences and Opportunities for Targeted Therapies
Authors: Joseph A. Caruso, Mylinh T. Duong, Jason P. W. Carey, Kelly K. Hunt, Khandan Keyomarsi
Journal: Cancer Research (2018)

Cyclin E, a regulatory subunit of cyclin-dependent kinase 2 (CDK2), is central to the initiation of DNA replication at the G
The analysis of T cell subset and the expression of PD-L1, HLA in esophageal squamous cell carcinoma.
Authors: Tomoya Sudo
Journal: Journal of Clinical Oncology (2018)

e16000 Background: Tumor infiltrating lymphocyte (TIL) is a significant factor to predict the prognosis of the esophageal squamous cell carcinoma (ESCC) patients. However, TIL is holding various subset and little is known about the locoregional TIL subset in ESCC. The purpose of this study is to investigate the proportion of the TIL subset and PD-L1and HLA component and to propose the proper indication of immune checkpoint inhibitor against ESCC. Methods: 1.Tissue sections were collected from 45 cases of esophagectomy patients. 2. Immunohistochemical staining was performed using the antibodies of CD3, CD8, CD45RO, Foxp3,PD-L1,HLA and AE1AE3. 3.Slides were scanned by NanoZoomer then digital pathological diagnosis was performed. 4. All images were processed through ImageJ and the quantity of the expression of molecules were counted. 5.Statistical analysis was performed comparing with the molecular expression pattern and clinicopathological variables. Results: The density of TIL was significantly higher in perimeter of the tumor than in center of the tumor. Clustering analysis was performed according to the TIL subsets then all cases were possible to be divided into five groups (Fig.1). Group 1-2 was immune deficient type and Group 3-5 was immune activating type. The disease free survival was significantly worse in Group 1-2. The expression of PD-L1 was significantly higher in Group 4 than in the other groups (Fig.2). The expression of HLA was not significantly different between the 5 groups (Fig.3). Conclusions: Anti PD-L1 immune checkpoint inhibitor supposed to be suitable to use in Group 4 cluster patients.
Biological and clinical manifestations of juvenile Huntington's disease: a retrospective analysis
Authors: Caterina Fusilli, Simone Migliore, Tommaso Mazza, Federica Consoli, Alessandro De Luca, Gaetano Barbagallo, Andrea Ciammola, Emilia Mabel Gatto, Martin Cesarini, Jose Luis Etcheverry, Virginia Parisi, Musallam Al-Oraimi, Salma Al-Harrasi, Qasem Al-Salmi, Massimo Marano, Jean-Paul Gerard Vonsattel, Umberto Sabatini, Georg Bernhard Landwehrmeyer, Ferdinando Squitieri
Journal: The Lancet Neurology (2018)
Incidence of pregnancy events among women with a malignant disease diagnosis.
Authors: Maria Alma Rodriguez, Lee Cheng, Alma Yvette DeJesus, Andrea Milbourne
Journal: Journal of Clinical Oncology (2017)

e18262 Background: Pregnancy concurrent with cancer is rare, but adds additional complexity to cancer management and treatment. Little information is available about incidence of pregnancy events among women with malignant diseases. We aimed to describe the incidence of pregnancy and the clinical characteristics of pregnant women with cancer who have received care at MD Anderson Cancer Center. Methods: This was an IRB-approved retrospective cohort study. We searched our electronic health records for women aged 12-50 years, with a cancer diagnosis, treated from January 1, 2011, to December 31, 2015. Results: Over 5 years, out of 30,670 unique female patients (pts), 315 (1.02%) had pregnancy events documented. The distribution of events by malignant disease site is shown in Table 1. When pregnancy was documented or diagnosed, the pts’ mean age was 31.3 years (range: 16.5-50.1) and mean gestational age was 17.8 weeks (range: 1.0-38.0). There were 18 documented terminations of pregnancy events (16 = 1st trimester; 2 = 2nd trimester). Of these pts, 83% (15/18) had received chemotherapeutic agents during 1st trimester = 11 cases; 2nd trimester = 2 cases; 12 weeks pre-conception = 2 cases. Conclusions: Most pregnant cancer pts can be safely treated. Most pregnancy terminations were associated with chemotherapy administration, prior to and within the first trimester of pregnancy. Thus, it is important to conduct pretreatment pregnancy screening and effective contraception when women of reproductive age are treated with a potentially teratogenic agent. In addition, urine pregnancy tests, recommended contraceptive methods, and menstrual history need to be documented during cancer-related therapy. [Table: see text]
The impact of tumor size on survival in T3 non-small cell lung-cancer with direct extension.
Authors: Clara H. Kim, Michelle C. Salazar, Jessica R. Hoag, Joshua E. Rosen, Brian N. Arnold, Daniel J. Boffa, Justin David Blasberg
Journal: Journal of Clinical Oncology (2017)

e20033 Background: Tumor size is an important prognostic variable that affects clinical decision-making in NSCLC including the use of adjuvant therapy. However, the association between tumor size and survival in a subset of patients who have T3 NSCLC with direct extension into nearby structures (T3 dx ) has not been explicitly characterized. We hypothesize that tumor size impacts survival and prognosis within this cohort. Methods: Patients with T3 dx in 2006-2013 who underwent lobectomy or pneumonectomy were identified in the National Cancer Database. Patients who received neoadjuvant therapy or had positive margins were excluded. Tumor size was categorized based on cutoffs used by current staging guidelines and patients were stratified by pathologic N stage (see table). Cox proportional hazard models were used to measure the independent impact of tumor size on survival. Results: Overall, 0.1-3cm tumors exhibit superior 5-year survival compared to 3.1-5cm and &gt;5cm tumors. Tumor size is significantly associated with survival in N0 patients but not in N1 and N2 patients. Use of adjuvant chemotherapy is associated with improved survival in the overall cohort and all subgroups; however, use of adjuvant chemoradiation may be associated with inferior survival in the overall cohort. Conclusions: Larger tumor size is associated with inferior survival in T3 dx in the absence of nodal disease. T3 dx requires a more tailored approach to adjuvant therapy than other T3 subgroups. Adjuvant chemotherapy appears to benefit all patients with T3 dx ; however, the role of adjuvant chemoradiation is less clear. [Table: see text]