tbuckley/cabot-search huggingface dataset:
A randomized phase II trial of second-line treatment for advanced soft tissue sarcoma comparing trabectedin, eribulin and pazopanib (2ND-STEP, JCOG1802).
Authors: Makoto Endo, Kazuhiro Tanaka, Yoshihiro Matsumoto, Hiroaki Hiraga, Shintaro Iwata, Satoshi Tsukushi, Munenori Watanuki, Toru Akiyama, Tsukasa Yonemoto, Robert Nakayama, Keisuke Ae, Hiroyuki Kawashima, Hiroyuki Tsuchiya, Hirohisa Katagiri, Akihito Nagano, Satoshi Takenaka, Tomoko Kataoka, Ryunosuke Machida, Haruhiko Fukuda, Toshifumi Ozaki
Journal: Journal of Clinical Oncology (2021)

TPS11580 Background: Soft tissue sarcomas (STS) are a rare type of malignancy, which comprises of a variety of histologies. Chemotherapy is the standard treatment for patients with advanced STS. Doxorubicin alone or in combination with ifosfamide is widely accepted as the first-line chemotherapy for advanced STS. While a combination with gemcitabine and docetaxel is regarded as a standard regimen of the second-line chemotherapy after failure of doxorubicin-based first-line regimen, the efficacy is not sufficient. Trabectedin, eribulin, and pazopanib are the candidates of the second-line chemotherapy for advanced STS, although there is no clear evidence showing which is better among those agents. The purpose of this clinical trial conducted by Bone and Soft Tissue Tumor Study Group of Japan Clinical Oncology Group (JCOG) is to determine the most promising regimen among trabectedin, eribulin and pazopanib as the test arm regimen in the future phase III trial of the second-line treatment for patients with advanced STS. Methods: The study, JCOG1802, is a multicenter, selection design, randomized phase II trial comparing trabectedin (1.2 mg/m 2 IV, every 3 weeks), eribulin (1.4 mg/m 2 IV, days 1 and 8, every 3 weeks) and pazopanib (800 mg PO, everyday) for patients with unresectable or metastatic STS refractory to doxorubicin-based first-line chemotherapy. Eligibility criteria include 16 year-old or older, unresectable and/or metastatic STS, an exacerbation within 6 months prior to registration, histological diagnosis of STS other than Ewing sarcoma, well-differentiated liposarcoma and myxoid liposarcoma, a history of chemotherapy for STS other than doxorubicin-based regimen, ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2, and sufficient organ function. Primary endpoint is progression-free survival (PFS), and secondary endpoints include overall survival, disease-control rate, response rate, and adverse events. To select the most promising regimen in median PFS (3 months in the worst regimen and 4 months in the best regimen) with a probability of at least 80%, a total of 120 patients will be enrolled from 37 institutions in Japan. After JCOG1802, a subsequent phase III trial comparing the winner of this study and a combination of gemcitabine and docetaxel will be planned. The study was activated at December 5, 2019 and 22 of planned 120 patients have been enrolled as of February 15, 2021. Clinical trial information: jRCTs031190152.
Anchored matching-adjusted indirect comparison (MAIC) of regorafenib (REG) versus cabozantinib (CAB) in advanced hepatocellular carcinoma (HCC).
Authors: Irina Proskorovsky, Mira Krotneva, Kirhan Ozgurdal, Savina Jaeger, Yun Su
Journal: Journal of Clinical Oncology (2021)

e16188 Background: REG and CAB, two therapies for second-line (2L) advanced HCC, have been evaluated vs. placebo (PBO) in randomized phase III trials, RESORCE (NCT01774344) and CELESTIAL (NCT01908426), respectively. In the absence of head-to-head studies, indirect treatment comparison (ITC) is needed to compare the efficacy and safety of REG vs. CAB. Anchored MAIC is an ITC method adjusting for cross-trial heterogeneity using PBO as the common comparator or anchor. Methods: Patient-level data from RESORCE were available to match the inclusion criteria and published baseline characteristics of CELESTIAL. 2L patients with prior sorafenib exposure of &gt;3 months were included in the analyses. Overall survival (OS), progression-free survival (PFS), and Grade 3/4 treatment-emerging adverse events (TEAEs) occurring in &gt; 10% of patients were compared. Matching was conducted for the following covariates, which were either imbalanced across trials or likely treatment effect modifiers (EMs): gender, region, Eastern Cooperative Oncology Group (ECOG), prior sorafenib duration, extrahepatic spread, macrovascular invasion, hepatitis B (HBV), hepatitis C (HCV), alcohol use, and alpha-fetoprotein (AFP) ≥400 ng/mL. Anchored MAIC were used to compare the relative effect of each treatment. To account for violation of the proportional hazards assumption, in addition to hazard ratios (HRs), restricted mean survival time (RMST) was estimated to quantify differences in OS and PFS. For safety, the relative effects were expressed as risk differences (RDs) (REG – CAB). Results: After matching, the effective sample sizes of REG and its PBO arm were 214 and 82, respectively. For OS, REG showed favorable although not statistically significant HR, and 30% longer mean survival with an RMST ratio approaching statistical significance. For PFS, there was no numerical difference in HR and no clinically meaningful difference based on RMST analyses (Table). REG showed lower incidence of diarrhea [RD of -7.1% (NE, NE)] and fatigue [RD of -6.3% (-14.6, 2.0)]. Conclusions: In this anchored MAIC, REG showed favorable OS and safety profile, especially for diarrhea and fatigue. No clinically meaningful difference was observed for PFS. The analysis could be limited by reduced sample size after matching and unobserved or missing EMs that could not be adjusted.[Table: see text]
National Cancer Institute (NCI) implementation of the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) broadening clinical trials eligibility criteria.
Authors: Andrea M. Denicoff, S. Percy Ivy, Katherine H. Worthington, Jinxiu Zhao, Nita Seibel, Grace E. Mishkin, Margaret M. Mooney, Richard F. Little
Journal: Journal of Clinical Oncology (2021)

6518 Background: The 2017 ASCO/Friends eligibility criteria guidelines recommend inclusiveness to promote generalizable trial results and clear rationale for necessary exclusion. These guidelines focused on brain metastases, minimum age for enrollment, HIV infection, and organ dysfunction and prior and concurrent malignancies. In September 2018, the NCI Cancer Therapy Evaluation Program (CTEP) implemented modernized protocol template language to operationalize these criteria. We evaluated utilization of the new language among CTEP-sponsored treatment trials. Methods: We evaluated protocols first approved by CTEP between 11/01/2018 and 4/30/2020. The most recent approved protocol version was evaluated for consistency with the new template language for brain metastases, HIV infection, prior or concurrent malignancies, minimum age, and cardiac, liver and kidney function. If a particular criterion was not relevant for a trial, it was not included in the analysis. We did not score age in pediatric or adult-specific trials (e.g. prostate). Results: 122 trials (71% early and 29% late phase) were identified and included in the analysis. Compliance with the new criteria language ranged from a high of 87.7% for liver function to a low of 11.5% for “new or progressive brain metastases” (table). Modernized criteria language was lacking in nearly 46% of trials in the use of concurrent or prior malignancy criteria and 31% of trials for the cardiac criteria. Of the 87 trials for non-localized disease or non-brain tumor trials, 64.4% did not address brain metastases, leaving it to investigator discretion. Thus, 75.9% of trials could theoretically enroll patients with brain metastases. Only 6 trials were considered relevant for patients &lt; 18 years old; 50% were consistent with the age criterion (not shown in table). Conclusions: Implementing ASCO/Friends eligibility criteria requires focused reviews during protocol development to ensure compliance. CTEP is using these findings to continue to improve its protocol review processes to broaden eligibility in clinical trials. Maximizing opportunities for diverse populations to participate in trials is a priority for the National Cancer Institute and CTEP will continue efforts to achieve this goal.[Table: see text]
IMMU-01. THE ONCOLYTIC VIRUS DELTA-24-RGD IN COMBINATION WITH AN AGONISTIC CD40 MAB INDUCES A DURABLE AND SYNERGISTIC ANTI-TUMOR IMMUNE EFFECT IN DIPG PRECLINICAL MODELS
Authors: Sara Labiano, Virginia Laspidea, Marc Garcia-Moure, Montserrat Puigdelloses, Oren J Becher, Candelaria Gomez-Manzano, Juan Fueyo, Ana Patiño-Garcia, Marta M Alonso
Journal: Neuro-Oncology (2021)

Abstract With a 2-year survival less than 20%, Diffuse Intrinsic Pontine Glioma (DIPG) is the principal cause of pediatric death. Despite recent advances in the current treatments, the outcome for children with DIPGs remains dismal. Since the approval of T-VEC for melanoma by the FDA, oncolytic adenoviruses have emerged as a promising therapeutic strategy for brain tumors. Thus, our group launched the first world clinical trial phase I with the oncolytic adenovirus Delta-24-RGD (DNX-2401 in the clinic) for newly diagnosed DIPG (NCT03178032), which has shown safety and feasibility. Despite DNX-2401 increases the recruitment of T cells into the tumor, they usually become inactive due to the suppressive tumor microenvironment evidencing the urgent need to improve this strategy focusing on the generation of effective long-term immune responses. Therefore, we decided to combine the Delta-24-RGD with the targeting of the costimulatory molecule CD40 in two unique orthotopic immunocompetent mouse models of DIPG. The activation of the CD40 receptor, which is expressed by antigen presenting cells (APC) such as microglia, macrophages and dendritic cells, is known to increase antigen presentation and enable T-cell priming and activation. Here, we have observed that in addition to Delta-24-RGD anti-tumor effects, the stimulation of CD40 on the tumor APCs results in a remodeling of the tumor immune compartment with a more efficient T-cell tumor infiltration. Of importance, there is an increase of the survival of mice treated with the combination as compared to single treatments or non-treated mice. In addition, the combination therapy induced a complete regression of tumors in 25% of treated mice indicating the development of long-term anti-tumor immunity. We believe that these results provide a translational breakthrough in the treatment of these lethal tumors and open the door for a future innovative clinical trial.
Comparing active immunotherapy efficacy of PD-L1 ≥ 50% NSCLC patients: A systematic review and meta-analysis.
Authors: Yi Hu, Xiaochen Zhao, Yuezong Bai, Longgang Cui, Fan Zhang
Journal: Journal of Clinical Oncology (2021)

e21139 Background: Several therapies based on immune checkpoint inhibitors (ICIs) have been approved as the 1L standard of care for PD-L1≥ 50% advanced non-small cell lung cancer (NSCLC). However, little is known about the difference in efficacy between different strategies. We conducted a systematic review and meta-analysis to help clinicians choose more reasonable treatment options. Methods: We searched PubMed, Cochrane library, Embase and major conference proceedings from January 2010 to December 2020 for randomized controlled trials that had available subgroup hazard ratios (HRs) for overall survival according to PD-L1≥ 50%. Only drugs met primary outcome or approved by FDA were included for analysis. The primary outcome was the difference in overall survival (OS). HRs and 95% CI were calculated for the pooled OS using a random-effects model. p&lt;0.05 was considered as statistical difference. Results: A total of 10 randomized controlled trials were included for this meta-analysis. The pooled HR and 95% CI for monotherapy, ICI plus chemotherapy and ICI plus ICI were 0.64 (0.55, 0.74), 0.64 (0.51, 0.79) and 0.70 (0.55, 0.90), respectively. There was no statistical differences between ICI monotherapy and ICI plus chemotherapy (HR 1.00, 95% CI 0.77- 1.30), between ICI monotherapy and ICI plus ICI (HR 0.91, 95% CI 0.69- 1.22) or between ICI plus chemotherapy and ICI plus ICI (HR 0.91, 95% CI 0.66- 1.27). Conclusions: For PD-L1≥ 50% NSCLC patients, active ICI monotherapies showed no different efficacy when compared with ICI combination therapies.
A Review of Acute Pancreatitis
Authors: David Alter, David D. Koch
Journal: JAMA (2021)

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Evaluation of the relationship between antenatal and postnatal tobacco smoke exposure and childhood cancers.
Authors: Nurdan Tacyildiz, Adil Güzel, Filiz Bakar Ateş, Derya Özyörük, Emel Cabi Unal, Handan Dincaslan
Journal: Journal of Clinical Oncology (2021)

e22011 Background: The incidence of childhood cancers increased by 1 % per year over the last three decades. Life style changes and increased variety of environmental exposures are accused of this trend. One of these environmental factors is cigarette smoking and parental smoking is the main source of tobacco smoke exposure of children. There are strong reasons for considering parental smoking behaviour as a risk factor for childhood cancers. Many tobacco related compounds are detected in fetal tissues, breast milk and tissues of children of smoking parents. However, it is hard to make causal relationship between parental smoking and childhood cancers. One of the reasons is the difficulty to detect tobacco smoke exposure. Questionnaires, commonly used method to detect tobacco smoke exposure, are prone to biases. Cotinine is the main metabolite of nicotine which is the abundant organic compound in tobacco and a good biomarker to detect tobacco smoke exposure. Methods: 104 newly diagnosed, 0-18 years aged pediatric cancer patients from two pediatric oncology centers ( Ankara University Children’s Hospital and Ankara City Hospital) and 99 healthy children aged 0-18 applied to the Ankara University Children’s Hospital participated our study. Parental smoking behaviours (preconceptional, during pregnancy and current smoking) and environmental tobacco smoke exposures (ETS) of children were compared between two groups. ETS exposures of cancer patients and healthy children were evaluated by hair cotinine ELISA analysis and questionnaire. For hair cotinine analysis, 30 mg of hair samples were taken from occipital part of scalp by a stainless scissors. Samples were processed according to manufacturer's instructions. Parents of two groups were surveyed about their smoking behaviours and ETS exposures of their children. Results: We found no differences between two groups by means of maternal preconceptional smoking, smoking during pregnancy and current smoking behaviours. Paternal preconceptional smoking and smoking during pregnancy rates were significantly low in cancer patients (p &lt; 0,05) according to questionnaire. Environmental tobacco smoke exposures were found statistically low in cancer patients according to questionnaire (p &lt; 0,05). However, quantitative exposure assessment by hair cotinine analysis revealed that cancer patients are exposed to tobacco smoke more than healthy children (p &lt; 0,001). Conclusions: Our findings support that smoking could be a risk factor for childhood cancers. This study also revealed that questionnaires could cause biases. We thought, social desirability bias of father of cancer patients could be a reason of their low smoking rates according to questionnaire. We suggest that cotinine analysis along with validated questionnaires can be used to prevent biases in studies of tobacco smoke in the etiology of childhood cancers.
Neoadjuvant radiotherapy to improve overall survival in resectable hepatocellular carcinoma.
Authors: Zhiwen Luo, Xu Che, Jianqiang Cai, Hong Zhao, Jing Jin, Yuan Tang, Bo Chen, Xinyu Bi
Journal: Journal of Clinical Oncology (2021)

e16178 Background: There is little evidence for the association between neoadjuvant radiotherapy (NRT) and improved overall survival (OS) in patients with resectable hepatocellular carcinomas (HCCs). This study aimed to determine whether NRT provides a survival benefit in these patients. Methods: We enrolled patients with resected HCC identified in the Surveillance, Epidemiology, and End Results database (2004–2015). Multiple imputation plus inverse probability of treatment weighting (IPTW) reduced selection bias. IPTW-adjusted Kaplan-Meier curves and IPTW-adjusted Cox proportional hazards models compared OS between different treatment groups. Sensitivity analyses tested the robustness of the estimates. Subgroup analysis identified the patients who could benefit most from NRT. Results: We enrolled a total of 11920 patients diagnosed between 2004 and 2015 in the study. Of these, 134 patients underwent NRT, the others underwent surgery alone (SA). The median OS in NRT was not approached, whereas in SA it was 52.0 (interquartile range, 34.25, 100.75) months. The 5-year IPTW-adjusted rates of OS in NRT versus SA were 65.3% and 46.6%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, NRT was associated with a significant OS benefit (hazard ratio [HR], 0.549; 95% confidence interval [CI], 0.327-0.921; p = 0.023). The results were robust in sensitivity analysis (E-value 2.39). Subgroup analysis demonstrated improved OS in the NRT cohort among younger patients (HR, 0.46; 95% CI, 0.26-0.83), N0 status (HR, 0.51; 95% CI, 0.28-0.94), and alpha-fetoprotein (AFP)-positive patients (HR, 0.28; 95% CI, 0.12-0.65). Conclusions: Patients with resectable HCCs may derive a survival benefit from NRT. Younger age ( &lt; 65 years) with a positive AFP level at N0 status could be indicators for NRT. These findings enlighten current guidelines to consider NRT in patients with resectable HCCs. The present study establishes a reasonable basis for further prospective studies.
Alternating gemcitabine/nab-paclitaxel (GA) and 5-FU/leucovorin/irinotecan (FOLFIRI) as first-line treatment for <i>de novo</i> metastatic pancreatic cancer (MPC): Safety and effect.
Authors: Brett A. Schroeder, Margaret T. Mandelson, Vincent J. Picozzi
Journal: Journal of Clinical Oncology (2021)

4125 Background: Both gemcitabine and 5FU-based chemotherapy have demonstrated efficacy in MPC. Alternating regimens may 1) reduce toxicity 2) slow resistant cancer biology emergence and 3) provide a broader platform for addition of other therapeutic agents. Alternating GA and FOLFIRI in MPC has been previously reported as part of the SEENA -1 trial,our own institution, and elsewhere (Picozzi et.al. GI Cancer Symposium 2017, Picozzi et.al, ASCO 2018 Assenat et,al, ASCO 2018). An extension of our institutional observations are reported here. Methods: Pt eligibility required the following: 1) biopsy proven de novo MPC, 2) no prior evidence MPC on CT, 3) ECOG performance status ≤ 2, and 4) bi-dimensionally measurable disease. Treatment (Rx) entailed gemcitabine 1000mg/m 2 and nab-paclitaxel 125mg/m 2 1, (8), 15 alternating every 8 wks (2 cycles) with FOLFIRI using standard dosing. Patients were radiographically re-staged every 8 wks. Rx was continued up to 48 wks; Rx thereafter decided by pt/MD. Results: 108 pts met eligibility requirements from 10/2015 and 12/2020. Pt characteristics included median age 68 ( range 35-81), ECOG PS 0/≥1 54%/46%, # diseases sites 1/≥1 62%/38%, liver /non-liver 76%/24%, biliary obstruction yes/no 40%/60%, C 19.9 NL/ &lt; 59XNL/ &gt; 59X NL 12%/32%/56%; median Ca 19.9 4598 With median f/u of 19.7 mo, 17 pts remain on Rx &lt; 48 wks, 35/91 (38%) completed 48 wks Rx, 56/91 (62%) pts progressed prior to 48 wks. Median # mos on Rx was 8.9. ≥ grade 3 heme toxicity included anemia 7%, neutropenia 9%, thrombocytopenia 5%. Neutrophil growth factors were not used in this pt cohort. ≥ 3 non-hem toxicity included neuropathy1%, nausea/vomiting 2%, mucositis 2%, diarrhea 1%. Disease control at 16 wks was 81% (35% PR/46% SD/16% PD, 95% CI 72-87%). Median OS was 13.7 mo (95% CI 10.9-18.7 mo). 6 /12/18/24 mo OS were 87%/55%/41%/ 20% respectively. Prognostic significance was seen with Rx &gt; vs &lt; 48 wks (21.1 vs 8.0 mo, p &lt;.0001), and ECOG PS 0 vs. ≥1 ( 17.8 vs. 10.9 mo, p = 0.03) Age, # metastatic sites, liver involvement, biliary obstruction and magnitude of CA 19.9 elevation all failed to achieve prognostic significance at the p &lt;.05 level. Conclusions: 1) Alternating GA/ FOLFIRI in MPC has a more favorable toxicity profile than standard regimens 2) Med OS appears superior to GA and competitive with FOLFIRINOX ; longer term (18/24 mo ) OS seemed particularly encouraging 3) ≥ 48 wks Rx and ECOG PS 0 were prognostically significant 4) Further investigation using this regimen including a) randomized comparisons, b) incorporation of molecular data and c) addition of additional agents seems indicated Updated survival data will be presented at the meeting