tbuckley/cabot-search huggingface dataset:
Myocarditis as a rare, yet serious adverse event associated with immune checkpoint inhibitors in patients with non-small cell lung cancer: Case series from a large community-based cancer center.
Authors: Mohamed Hendawi, Luke Peterson, Eyob ale Tadesse, Frank M. Wolf, Thomas D. Brown, Michael A. Thompson
Journal: Journal of Clinical Oncology (2021)

e21047 Background: Patients (pts) with lung cancer and other cancers treated with immune checkpoint inhibitors (ICI) may experience immune related adverse events (irAE). These can present with variable severity and with single- or multi-organ involvement including pneumonitis, colitis, hepatitis, and myocarditis/pericarditis. The incidence of myocarditis has been reported between 0.06% and 2.4% and is associated with a high mortality (25% to 50%). This retrospective review of real-world data (RWD) investigates myocarditis as a high-grade adverse event in pts with lung cancer treated with ICIs. Methods: Pts were identified and characterized using RWD in the Syapse Learning Health Network platform from 2010 to 2020 at Advocate Aurora Health Care. Eligible pts included: ≥18 years old; histologically confirmed NSCLC; and myocarditis diagnosis by ICD codes. Additional chart review was performed to confirm timing of ICI treatment and myocarditis. All pts identification and review were performed after IRB review. Results: 12,686 pts with non-small cell lung cancer were eligible for review. The median age at diagnosis was 70; 54% were female; 86% were White and 12% were Black; 1,975 (15.6%) were treated with an ICI and of those 4 cases (0.2%) of myocarditis were identified. All 4 pts were White females, ages 46, 59, 65, and 74 years. Pathology included lung adenocarcinoma (3) and an undifferentiated lung carcinoma (1). All pts had metastatic disease, and none had a prior history of cardiac disease. ICIs were pembrolizumab (2), durvalumab (1), and nivolumab (1). Median time from initial dose of ICI to diagnosis of myocarditis was 62 days [range: 42-185]. All 4 pts presented with chest pain and elevated troponin T [median 0.07 ng/ml (range: 0.06-0.08)]. All pts had echocardiography at the time of diagnosis, and 2 pts had cardiac MRI that confirmed myocarditis. 3 pts were treated with a prednisone taper. 1 pt died of recurrent congestive heart failure and ventricular tachycardia despite rescue attempt with high dose corticosteroids. 2 pts had additional concomitant irAEs of hypothyroidism/colitis, and thyroiditis/pneumonitis, respectively. Conclusions: Many irAEs are reversible. This RWD analysis confirms that clinically evident myocarditis is a rare but serious adverse event of ICI therapy. Early consideration, diagnosis, and intervention may help prevent poor outcomes. Termination of ICI therapy along with initiation of corticosteroids constitute the current standard of management. Further research is warranted to better identify high risk groups, surveillance measures, and improved management of ICI associated myocarditis.
A Review of Acute Pancreatitis
Authors: Anshuman Elhence, Soumya Jagannath Mahapatra, Pramod Kumar Garg
Journal: JAMA (2021)

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Indicatives of palliative care in patients with lung cancer treated in the Brazilian public health system.
Authors: Thiago Henrique Mascarenhas Nébias, Munir Murad Junior, Marcos Antonio da Cunha Santos, Mariangela Cherchiglia
Journal: Journal of Clinical Oncology (2021)

e24007 Background: In the last decade, a growing body of evidence has demonstrated that palliative care improves outcomes such as QOL, symptom burden, survival and decreases resource utilization. However, many patients eligible for PC are not referred to it or receive these services only in the last phase of their illness. Significant barriers explain the lack of access to PC, including identifying patients who would benefit from this approach. The aim of this study is to identify indicatives of palliative care in patients with lung cancer in Brazil in order to improve access. Methods: Prospective non-concurrent cohort carried out from a database developed through probabilistic and deterministic linkage of data from information systems of the Brazilian Public Health System. Study population was composed of all patients who started cancer treatment between 2009 and 2014 and who was hospitalized at least one time after starting treatment. To address the indication for palliative care, patients whose death occurred within one year after the first hospitalization were selected. Logistic regression models were used to assess the association between death in one year and sociodemographic, clinical and treatment-related variables. Results: A total of 27,634 patients diagnosed with lung cancer started cancer treatment in that period and 17,805 (64%) died one year after the first hospitalization. Among the deceased patients, the median age was 63 years, 59,8% of them were in stage IV, 32.4% in stage III and the majority received chemotherapy as their first treatment (72,3%). In this sub-group, 44,3% lived in the southeastern region of the country and 63,3% were male. Furthermore, 91% of the patients required emergency hospitalization and 20,1% were admitted in ICU units. The multivariate analysis revealed that being male (OR=1.2; CI, 1.13-1.28), live in the north region (OR=1.38, CI, 1.13-1.69) and having an older age (40-59 years, OR= 1.32; CI, 1.07-1.63; 60-79 years, OR=1.48; CI, 1.2-1.83; 80 or more years, OR=1.62; CI, 1.26-2.08) were associate with the outcome. Patients that were diagnosed with stage IV lung cancer (OR=1.99; CI, 1.7-2.33) and those who received radiotherapy (OR=7.83; CI, 6.86-8.94) as first treatment presented higher odds of dying in one year after the first hospitalization. In addition, patients who were hospitalized on an emergency basis (OR=10.94; CI, 10.19-11.74) and those who were admitted in ICU units (OR= 1.17; CI; 1.07-1.26) had higher association with the outcome. Interestingly, patients that took more than 60 days to initiate cancer treatment (OR=0.69; CI, 0.64-0.74) presented lower association with dying in one year. Conclusions: Our study demonstrates variables that can be used to identify patients who may benefit most from PC. Moreover, this indicatives can be easily assessed in the moment of hospitalization.
BIOL-11. THE ROLE OF ABERRANT EXPRESSION OF PRDM6 IN THE DEVELOPING CEREBELLUM AND IN GROUP 4 MEDULLOBLASTOMA
Authors: Christin Schmidt, Annika Carlson, William Weiss, Bjoern Schwer
Journal: Neuro-Oncology (2021)

Abstract Group 4 medulloblastoma is the most common medulloblastoma subgroup with an intermediate prognosis and a high incidence of metastasis and late-onset relapse cases. Despite several comprehensive genomic studies in medulloblastoma, Group 4 medulloblastomas lack a unifying oncogenic driver and treatment targets. This subgroup is characterized by recurrent genetic alterations in chromatin modifiers, amplification of stemness genes, and enhancer hijacking events. 17% of Group 4 medulloblastoma cases are characterized by enhancer hijacking through tandem duplication of SNCAIP, resulting in high expression of PRDM6, a putative transcriptional repressor and histone methyltransferase. PRDM6 amplified medulloblastoma cases show additional mutations in other chromatin regulators, such as KDM6A, KMT2C and KMT2D, ZMYM3, and high MYCN expression. In this project, we investigate the impact and oncogenic potential of sustained PRDM6 expression in early neural stem cell populations and the developing mouse cerebellum. We drive expression of PRDM6 in human iPSC-derived neuroepithelial stem cells (NESCs) with and without high MYCN expression to study its implications in tumorigenesis. To test for tumor growth in vivo and changes in tumor progression as a function of PRDM6 activity, NESCs are injected into the cerebellum of adult mice. In order to elucidate impact of PRDM6 activity during embryonic cerebellar development, we also introduce PRDM6 expression into mouse embryonic stem cells (ESCs) for analysis via a new, in vivo cerebellar blastocyst complementation model. The latter approach is designed to ablate and repopulate early granule neural precursor cells in the embryonal cerebellum with progenitors derived from injected PRDM6-ESCs and thus to recapitulate pre- and postnatal cerebellar development in vivo. Together, our studies aim to understand the role of PRDM6 during normal cerebellar development and tumorigenesis and advance the understanding of the genetic drivers for Group 4 medulloblastoma.
Predictive Simulation Modeling in JAK2-Mutant MPNs Identified Ruxolitinib and Sorafenib As a Synergistic Drug Combination for Disease Modifying Therapy
Authors: Peter P. Sayeski, Leylah M. Drusbosky, Neeraj Kumar Singh, Anusha Pampana, Shahabuddin Usmani, Mohammed Sauban, Abha Kushwaha, Anu Ramakrishnan, Taher Abbasi, Shireen Vali, Christopher R. Cogle
Journal: Blood (2017)
Abstract #4652: CD70 expression in multiple types of carcinomas: new targets for auristatin-based anti-CD70 antibody-drug conjugate, SGN-75
Authors: Leia Smith, Heather Kostner, Steven Duniho, Albina Nesterova, May Sutherland, Changpu Yu, Kristine Kim, Kristine Gordon, Julie McEarchern, Che-Leung Law, Maureen Ryan
Journal: Cancer Research (2009)

CD70, a transmembrane type II protein, is a member of the tumor necrosis factor (TNF) family. CD70 has been previously reported to be highly expressed in solid tumors (renal cell and nasopharyngeal carcinomas) as well as hematologic malignancies and has very limited expression in normal cells (activated lymphocytes, dendritic cells). An extensive expression profiling study for CD70 in carcinomas has been a challenge in the past due to a lack of an anti-CD70 reagent that works well in formalin-fixed paraffin embedded (FFPE) tissues. Murine monoclonal antibodies were generated and validated for specific CD70 staining and a protocol for immunohistochemical (IHC) analysis using FFPE samples was developed. Tissue microarray analysis of various types of tumors confirmed CD70 expression in kidney cancers (70% of cases). In addition, we report novel detection of significant CD70 expression in carcinomas such as pancreatic (25% of cases), larynx/pharynx (22%), ovarian (15%), skin (13%), lung (10%), and colon (9%). We also detected CD70 expression in tumor cell lines from the same indications by IHC and flow cytometric analyses. Using CD70+ ovarian and pancreatic cell lines, we show in vitro efficacy of our anti-CD70 antibody-drug conjugate, SGN-75. These results demonstrate the potential application of anti-CD70 ADCs for treatment of ovarian and pancreatic cancers.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4652.
Real-world clinical adverse events (AEs) among nonmetastatic castration-resistant prostate cancer (nmCRPC) patients treated with novel anti-androgen (AA) therapies: A retrospective database study.
Authors: Stephen J. Freedland, Sreevalsa Appukkuttan, Jianying Yao, Yuxian Du, Jacqueline Parkin, Jamie Partridge, Sheldon Kong
Journal: Journal of Clinical Oncology (2021)

e18675 Background: Novel AA agents, such aspalutamide (Apa), enzalutamide (Enza) and darolutamide (Daro) are approved for the treatment of nmCRPC. In clinical trials, they were associated with AEs such as fatigue, fractures and falls. This study aimed to describe the real-world incidence of AEs among nmCRPC patients who initiated treatment with AA agents. Methods: Claims from Optum Clinformatics Data Mart, a large single-payer claims database were used to retrospectively identify adult males with prostate cancer (PC), evidence of castration, absence of metastases codes and &gt;1 claim for AA therapies Apa and Enza (index date) from Jan 2017 through Dec 2019. Daro, a more recently approved AA, was not included due to lack of data. Incidence of central nervous system (CNS) (including but not limited to fatigue, falls and cognitive impairment) and any AE (fracture, rash, hypertension among others) were estimated and Kaplan-Meier analyses were used to quantify the median time from therapy initiation to clinical event occurrence. Multivariable Cox-proportional hazards model was used to identify clinical event predictors. A washout of previous AE events in the 1-year baseline was applied to identify true incident events. Results: A total of 605 patients (156 Apa and 449 Enza) were included in the study. The majority were ≥65 yrs (94.0%), white (56.0%), resided in the south (47.1%), and had Medicare insurance (86.4%). Almost all were medically castrated (99.0%) and mean Charlson Comorbidity Index (CCI) Score was 2.28. Incidence rates of all clinical events and CNS-related events were high (71.2% and 46.1%, respectively) with no major differences between Apa and Enza (Table). The median time from Apa or Enza treatment initiation to any clinical event was 71 and 64 days, respectively, and 282 and 209 days for CNS-related events, respectively. Significant predictors of having any events included age &gt;75 yrs and high CCI score. Similar predictors were found for any CNS events. Conclusions: More than 70% of Apa and Enza treated nmCRPC patients had at least 1 clinical AE. Given the lack of a control cohort, further study is needed to assess whether these events are related to AAs or represent inherent risks of these events in the underlying population of largely older men with advanced PC. Future studies are warranted with all approved agents including Daro. [Table: see text]
Doublet (FOLFOX or FOLFIRI) versus triplet (FOLFOXIRI) backbone chemotherapy regimen as first-line treatment of metastatic colorectal cancer: A meta-analysis and systematic review.
Authors: Vishal Jindal, Ruby Gupta, Kamal Kant Sahu, Mandeep Singh Rahi, Michael J. Stender, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2021)

3593 Background: Doublet chemotherapy FOLFOX and FOLFIRI are standard for first‐line treatment of metastatic colorectal cancer (mCRC). Recently, use of triplet chemotherapy FOLFOXIRI has shown an increased anti-cancer activity but still there is uncertainty regarding first line backbone chemotherapy. Therefore, we conducted this metanalysis to determine the efficacy, safety and outcome of triplet vs doublet chemotherapy. Methods: The study protocol was published at PROSPERO (CRD42020166745) and prepared as per PRISMA guidelines. Total 10 studies were included, with sample size of 1536 participants in triplet arm and 1535 participants in doublet arm. The primary outcome is Response rate (RR) and secondary outcomes are Progression-free survival (PFS), Overall survival (OS), post chemotherapy radical (R0) surgical resection rate of metastases. Quantitative synthesis was performed using “R” statistical package. Dichotomous outcomes were summarized using odds ratio (OR) and time to event data was summarized using hazard ratio (HR). Results: A total of 678 articles were retrieved. The Medline article search gave a result of 271 article, Embase 296, the Cochrane Library 100 and Clinical tral.gov 11, when searched through April 2020. Total 10 studies were included. All the studies were randomized, open-label, multicenter study. Out of the 10 trials 5 each were phase II and phase III studies. The pooled odds ratio for RR was 1.66 (95% CI 1.42 to 1.93) and PFS was (HR, 0.70; 95% CI, 0.63–0.78) in favor of triplet chemotherapy. There was significant improvement in radical resection (R0) of metastases (OR 1.59; 95% CI, 1.27–1.98) in triplet arm. Triplet arm was also associated with increased toxicity especially neurological events 2.51(0.88-7.16), diarrhea 2.40(1.74-3.31), neutropenia, 2.23(1.71-2.90) and thrombocytopenia 1.94(1.05-3.59). Conclusions: Findings in this meta-analysis showed that FOLFOXIRI significantly improves the PFS, RR, OS, and R0 resection rate of overall metastases over the doublet chemotherapy. The incidence of fatal adverse events was found to be more in triplet chemotherapy compared to doublet therapy. Therefore, we concluded that with moderate evidence FOLFOXIRI provide clinically meaningful efficacy benefit at cost of increased toxicity.[Table: see text]
Impact of COVID19 pandemic on the hospitalization burden of cancer patients: Results of a quasi-experimental study.
Authors: Juan Cristobal Sanchez, Beatriz Nuñez García, Alberto Ruano, Mariola Blanco, Blanca Cantos Sanchez de Ibarguren, Miriam Mendez, Arturo Jose Ramos-Vegue, Ana Maria Morito, Ramon Aguado, Mariano Provencio-Pulla
Journal: Journal of Clinical Oncology (2021)

e13527 Background: The SARS-CoV-2 (COVID19) pandemic has had a huge impact on health care, leading to the declaration of a “state of alarm” in many countries. This situation has possibly conditioned the care of cancer patients, compromising hospitalization resources due to healthcare restraints. We aim to analyze the impact of the COVID19 pandemic on the hospitalization of cancer patients during the “state of alarm” in an Academic Hospital in Madrid, considered one of the most affected regions in the World during the first wave of the pandemic in Europe. Methods: Quasi-experimental study with similar controls collected in the same period of the previous year from cancer patients admitted to the Medical Oncology (MO) department of the Puerta de Hierro University Hospital in Madrid. Patients were selected from diagnoses coded by the ICD-10 obtained from discharge reports in the Admission Department. Cancer and viral pneumonia codes (excluding influenza) were analyzed. Admission to Internal Medicine (IM) department was also explored to describe hospitalization due to COVID19 pneumonia. We defined two groups: pandemic (03/14/20 - 06/20/20) and control (pre-pandemic) (03/14/19 - 06/20/19). Results: 74 cancer patients were admitted to MO department in 2020, while 162 admissions were recorded for the equivalent period in 2019 (- 54%). No differences were observed related to sex and age. In 2020, emergency and programmed admissions decreased by the same proportion, and no difference in mortality was observed. Admissions for all neoplasms decreased, but with higher magnitude in breast cancer. Viral pneumonia (no influenza) in cancer patients were mostly admitted to IM (96%) rather than MO department. 79 cases were identified in 2020, 22 in 2019 (p &lt; 0.001), with a non-significant increase in mortality in patients with pneumonia: 25,3% in 2020 and 13,6% in 2019. Conclusions: The COVID 19 pandemic seriously impacted cancer hospitalization care, decreasing admissions to the MO department in half compared to the equivalent period. We observed a reduction in admissions through all neoplasias. Admissions due to viral pneumonia in cancer patients increased 3.5 times, mostly admitted to IM changing the dynamics of cancer hospitalization burden and compromising resources. A non-significant increase in mortality from viral pneumonia was observed. The analysis of hospitalizations through administrative data can allow better management of resources and facilitate rapid decision-making in a pandemic situation yet to be resolved.[Table: see text]
Al18F-NOTA-FAPI-04 Outperforms 18F-FDG PET/CT in Identifying the Primary Lesion and Rare Metastases From Gastric Cancer
Authors: Ying Kou, Zhiwei Yao, Zhuzhong Cheng
Journal: Clinical Nuclear Medicine (2021)

A 45-year-old woman with gastric cancer underwent FDG PET/CT for initial staging. However, the primary and the metastatic lesions were observed with low or no FDG uptake. Then, the patient underwent fibroblast-activated protein inhibitor PET/CT 2 days later, which demonstrated more lesions and much higher tumor-to-background contrast than FDG PET/CT did.
Predict the benefit of metronomic capecitabine maintenance in early-stage triple-negative breast cancer: Results from the SYSUCC-001 study.
Authors: Zhongyu Yuan, Xin Hua, Wang-Zhong Li, Heng Huang, Li Cai, Ying Lin, Lehong Zhang, Qianjun Chen, Jia-Jia Huang, XiWen Bi, Wen Xia, Shu-Sen Wang, Fei Xu, Ruoxi Hong, Kuikui Jiang, Yanxia Shi, Cong Xue, Xin An, Jun Tang, Xi Wang
Journal: Journal of Clinical Oncology (2021)

521 Background: Recent clinical trials and meta-analysis have suggested the benefit of adding capecitabine to standard chemotherapy in early-stage triple negative breast cancer (TNBC). We aimed to develop an individualized prediction model to quantify the clinical benefit of metronomic capecitabine maintenance in TNBC. Methods: Patients from the SYSUCC-001 trial, randomized to standard treatment with or without metronomic capecitabine maintenance, were pooled. Candidate covariates included age, tumor size, lymph node, histological grade, Ki-67 percentage, lymphovascular invasion, chemotherapy regimen and capecitabine medication. The primary endpoint was disease-free survival (DFS). The nonlinear effect of continuous covariate was modelled by restricted cubic spline. We developed a survival prediction model using the Cox proportional hazards model. Results: A total of 434 patients were recruited (306 in development cohort and 128 in validation cohort). The estimated 5-year DFS in the development cohort and validation cohort were 77.8% (95% CI, 72.9-82.7%) and 78.2% (95% CI, 70.9-85.5%), respectively. Age and lymph node had significant nonlinear effects on DFS. Four covariates significantly associated with DFS in the final prediction model were age, lymph node, lymphovascular invasion and capecitabine medication. The model demonstrated suitable calibration and fair discrimination ability with a C-index of 0.722 (95% CI, 0.662-0.781) and 0.764 (95% CI, 0.668-0.859) in the development cohort and validation cohort, respectively. We design an easy-to-use online calculator based on the model, capable of predicting capecitabine maintenance benefit. Conclusions: The evidence-based prediction model could identify those patients who most warrant metronomic capecitabine maintenance and thus help treatment decision making in daily clinical practice. Clinical trial information: NCT01112826.