tbuckley/cabot-search huggingface dataset:
Integrating psychosocial care into routine cancer care: A stepped-wedge design cluster randomized controlled trial (SWD-RCT) to evaluate effectiveness of the HuCare Quality Improvement Strategy (HQIS) on health-related quality of life (HRQoL).
Authors: Rodolfo Passalacqua, Elisa Iezzi, Maria Antonietta Annunziata, Claudio Verusio, Carmine Pinto, Mario Airoldi, Marcello Aragona, Francesca Caputo, Saverio Cinieri, Paolo Giordani, Stefania Gori, Rodolfo Mattioli, Silvia Novello, Antonio Pazzola, Giuseppe Procopio, Antonio Russo, Cosimo Sacco, Giuseppina Sarobba, Filippo Zerilli, Caterina Caminiti
Journal: Journal of Clinical Oncology (2019)

6515 Background: Cancer patients (pts) often do not receive evidence-based psychosocial care. We evaluate the effects of an implementation strategy we previously demonstrated feasible, which includes communication skill training for all physicians and nurses; four support visits at the centers by an improvement team to assist staff in identifying obstacles, finding solutions, and strengthening motivation; screening for distress and social needs; individualized pts' education with a referring nurse; use of a question prompt list. Methods: Multicenter incomplete SWD-RCT with 3 clusters of 5 centers each. Consecutive outpatients requiring medical treatment and diagnosed in the previous 2 months were eligible. Primary endpoint: difference of at least one of the 2 domains of HRQoL emotional or social functions, at 3 months from baseline, in pts of the centers that implemented the HQIS vs standard of care (SoC). Secondary endpoints include: patient mood, long-term effect, overall HRQoL. Analyses were performed using a beta-binomial regression model. Results: 762 pts were enrolled. At baseline, 41% showed high anxiety (HADS-A&gt;7), and 88% had at least one psychosocial need. 299 health professionals attended 3-day courses (84% of all clinical staff). 647 pts (85%) were available for analysis. The 315 pts who received HQIS exhibited better quality of life for the emotional domain than those assigned to SOC (OR=1.115, p=0.016). Pts who showed the greatest improvement were the older (OR=1.003, p=0.035), had lower anxiety basal levels (OR=0.853, p&lt;0.001), and social needs were met (OR=1.182, p&lt;0.001). The difference was not significant for the social domain (OR=0.955, p=0.353). The HQIS’s long-term effect was confirmed for the emotional domain at 12 months. No effect on mood (HADS-D) and overall HRQoL was observed. Conclusions: To our knowledge this is the first RCT demonstrating the effectiveness of a psychosocial care implementation strategy on cancer patients’ emotional well-being. Clinical trial information: NCT03008993.
Case 32-1988
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Philip C. Amrein, Judith A. Ferry
Journal: New England Journal of Medicine (1988)

Presentation of CaseA 47-year-old man was admitted to the hospital because of jaundice.He was in a stable state of health until 32 months earlier, when he consulted a physician because of a respiratory tract infection and anemia was found. Colonoscopic examination showed a tumor in the right side of the colon. A right colectomy was performed at another hospital. Microscopical examination of the excised tumor revealed a poorly differentiated adenocarcinoma of the signet-ring-cell type, with invasion of the submucosa and metastasis to one of five pericolonic lymph nodes; the tumor was classified as Dukes' class C. The patient . . .
Abstract 15483: Building a New Drug Screening System for Evaluating Drug Response and Toxicity by Three Dimensional Cardiac Constructs Derived From Human Induced Pluripotent Stem Cells
Authors: Maki Takeda, Shigeru Miyagawa, Satsuki Fukushima, Atsuhiro Saito, Emiko Ito, Akima Harada, Ryohei Matsuura, Yuriko Matsunaga, Noriko Mochizuki-Oda, Michiya Matsusaki, Mitsuru Akashi, Yoshiki Sawa
Journal: Circulation (2016)

Background: The establishment of innovative drug screening system may be crucial for the development of new therapeutic agents in terms of costs and acceleration in the pace of drug discovery. Alth...
Effect of trilaciclib, a CDK 4/6 inhibitor, on myelosuppression in patients with previously treated extensive-stage small cell lung cancer receiving topotecan.
Authors: Lowell L. Hart, Zoran Gojko Andric, Maen A. Hussein, Renata Ferrarotto, J. Thaddeus Beck, Janakiraman Subramanian, Davorin Z. Radosavljevic, Dragana Jovanovic, Krishna Kishore Pachipala, Miroslav Samarzija, Bojan Zaric, Wahid Tewfik Hanna, Raid Aljumaily, Taofeek Kunle Owonikoko, Rajesh K. Malik, Shannon R. Morris, Misha L. Johnson, Zhao Yang, Steven Adler, David R. Spigel
Journal: Journal of Clinical Oncology (2019)

8505 Background: Multi-lineage myelosuppression is an acute toxicity of cytotoxic chemotherapy leading to hematologic adverse events and dose reductions and delays. Current therapies are lineage specific and administered after chemotherapy damage.Trilaciclib (T), a highly selective, reversible CDK4/6 inhibitor, is designed to preserve hematopoietic stem and progenitor cells and immune system function during chemotherapy (myelopreservation). We have shown that T mitigates myelosuppression in patients with newly diagnosed extensive-stage small cell lung cancer (ES-SCLC) receiving 1 st -line chemotherapy. Methods: In this blinded, placebo-controlled, multicenter Phase 2 study, patients with previously treated ES-SCLC were randomized to T (240 mg/m 2 ) + 0.75 mg/m 2 topotecan, T (240 mg/m 2 ) + 1.5 mg/m 2 topotecan, or placebo (P) + 1.5 mg/m 2 topotecan IV on days 1-5 of 21-day cycles. Patients had access to standard supportive care, except in cycle 1 where prophylactic growth factors were not allowed. Eligible patients had adequate organ function, measurable disease, ECOG PS 0-2, and disease progression during or after prior 1 st /2 nd -line chemotherapy. Objectives included safety, tolerability, measures of myelosuppression and tumor efficacy. Results: 91 patients were randomized: 30 patients received T + 0.75 mg/m 2 topotecan, 32 patients received T + 1.5 mg/m 2 topotecan and 28 patients received P + 1.5 mg/m 2 topotecan. In patients receiving 1.5 mg/m 2 topotecan, T treatment reduced occurrence [40.6% (T) vs 75.6% (P), p = 0.016], and duration in cycle 1 [2 days (T) vs 8 days (P), p = &lt; 0.0001] of severe neutropenia. T-treated patients had fewer RBC transfusions on/after 5 weeks on study, GCSF administrations, and all-cause dose reductions. Chemotherapy efficacy was comparable in both arms (P and T) treated with 1.5 mg/m 2 topotecan (median PFS (T) 4.2 months vs (P) 4.2 months, HR = 0.83). OS data is immature. Conclusions: T combined with topotecan mitigated chemotherapy-induced myelosuppression and improved tolerability of topotecan vs P. Results suggest the addition of T to cytotoxic chemotherapy for the treatment of ES-SCLC is clinically beneficial. Clinical trial information: NCT02514447.
Spatially-resolved, multiplexed quantification of protein and mRNA distribution and abundance in colorectal cancer tumor microenvironment with multiple modalities of NanoString GeoMx Digital Spatial Profiler.
Authors: Gokhan Demirkan, Chris Merritt, Douglas Hinerfeld, Giang Ong, Kristina Sorg, Gayathri Balasundaram, Dwayne Dunaway, Gary K Geiss, Joseph M Beechem
Journal: Journal of Clinical Oncology (2019)

e14218 Background: Characterization of the spatial distribution and abundance of proteins and mRNAs with morphological context within tissues enables a better understanding of biological systems in many research areas, including immunology and oncology. However, it has proven difficult to perform such studies in a highly multiplexed manner. To address this unmet need, we have developed a novel optical-barcode based microscope and tissue-sampling platform designed to simultaneously analyze hundreds of proteins or mRNAs on a single FFPE section from distinct tissue spatial regions. Methods: Using colorectal cancer FFPE sections we spatially resolve protein and mRNA expression of immune-oncology targets and present a series of modalities and associated applications for the GeoMx Digital Spatial Profiler platform. Results: Microsatellite stable (MSS) or instable (MSI) colorectal tumors will be characterized to evaluate active and suppressive immune mechanisms in both immune dense regions and tumor versus stroma by utilizing segment profiling. Regions from the invasive margins and tumor centers will be investigated with contour profiling to define different immunosuppressive and activated immune phenotypes. Evaluation of tumor versus stroma will also identify pathways related to each compartment that are different between MSI and MSS tumors. These techniques can be used to discover drug mechanism of action or immune activation status, as well as to facilitate prediction of treatment response and disease progression or investigation of specific rare cell populations’ molecular profiles. Conclusions: This study will demonstrate multiplexed pathway-level protein and gene expression analysis from discrete regions within a colorectal tumor (tumor center and immune invasive margin), enabling systematic interrogation of immune activity in FFPE samples. Further studies could eventually lead to the identification of unique localized immune characteristics to guide combination therapeutic approaches.
Does systemic treatment add value to stereotactic body radiation therapy for locoregional control in head and neck squamous cell carcinoma patients?
Authors: Andrea M Tufano, James Newman, Emile Gogineni, Jessie L Karten, Doru Paul, Maged Ghaly, Nagashree Seetharamu
Journal: Journal of Clinical Oncology (2019)

e17505 Background: Stereotactic body radiotherapy (SBRT) has been shown to provide locoregional control in head and neck squamous cell carcinoma (HNSCC) patients (pts) who are not candidates for curative procedures due to poor performance status, comorbidities, or radiation dose limitations from prior treatment. The addition of chemotherapy (chemo) and/or cetuximab (CET) is hypothesized to improve outcomes compared to SBRT alone, but there is limited data on comparative effectiveness. We compared outcomes of pts treated with SBRT vs. SBRT + chemo and/or CET using retrospective observational data from our institution. Methods: We identified new and recurrent HNSCC pts treated with SBRT +/- systemic therapy from 2012 to 2018. Age, Charlson Comorbidity Index (CCI) and stage were recorded. Primary outcome was locoregional disease control rate based on Modified Response Evaluation Criteria in Solid Tumors on 3-month post-treatment imaging. Secondary outcome was overall survival (OS) at 1 year. Pts were divided into 4 groups: SBRT, SBRT+chemo, SBRT+CET, and SBRT+chemo+CET (cohorts A, B, C and D, respectively). Results: 90 pts with median age of 73 years and median follow-up of 11.5 months were included. 94.4% were stage III or IV, and 68.9% had recurrent disease. The most commonly utilized chemotherapy was carboplatin and paclitaxel. Cohorts A, B, C and D constituted 28.9%, 31.1%, 31.1% and 8.8% respectively. Groups were well matched except for pts in Cohort A being significantly older than those in Cohort B (74.9 vs. 68.4 years; p = 0.01). Average CCI estimated 10-year survival was 8.4%. There was a trend towards improved locoregional control at 3 months in Cohort B vs. A (57.1% vs. 34.6%, p = 0.09), and improved OS at 1 year (46.4% vs. 23.1%; p = 0.07). These trends were not observed in comparisons between other cohorts. Conclusions: Chemo + SBRT may improve disease control as well as 1 year OS in HNSCC pts who do not qualify for curative procedures. Given the younger age of pts receiving chemo, selection bias cannot be excluded. Prospective studies with larger patient cohorts are needed to further evaluate the benefits and toxicities of adding systemic treatment to SBRT in this population.
Exclusive: Unredacted report reveals patient safety concerns at “dysfunctional” Morecambe Bay urology unit
Authors: Clare Dyer
Journal: BMJ (2019)

A 2016 report by the Royal College of Surgeons (RCS) into the urology service at Morecambe Bay University Hospitals NHS Foundation Trust has been released for the first time, revealing a dysfunctional surgical team, allegations of bullying and racism, and a risk to patient safety.

A redacted version of the RCS report has come into the public domain after a freedom of information request by the area’s local newspaper, the Mail . But The BMJ has seen the full, unredacted report.

The six consultant urologists at the time of the report’s focus included Peter Duffy, a joint clinical lead who reported safety concerns to the Care Quality Commission in 2015 and later resigned, claiming that his working life had been made so difficult that he had to leave …
RAS mutations in patients with metastatic colorectal cancer in Central America and the Caribbean.
Authors: Luis Garcia-Aceituno, Noe Castro, Francisco Alvarado, Hugo Raul Castro Salguero, Yong Pain Loo, Jenny Lissette Castro, Pier Angelo Ramos, Angela Margarita Cabreja, Finlander Rosales, Allan Barillas, Allan Ramos-Esquivel, Jorge Umanzor, Gerardo Antonio Umanzor Funez, Mario Guardia, Ludwing Alexander Bacon Fonseca
Journal: Journal of Clinical Oncology (2019)

e15126 Background: Metastatic colorectal cancer (MCRC) survival has been improved in the last decade due to the identification of predictive and prognostic factors such as RAS gene status and also by the addition of targeted therapies to chemotherapy schemes. RAS mutation, a prognostic factor but must importantly a predictive factor for tumor response to monoclonal antibodies against the epidermal growth factor receptor in MCRC, has been reported between 16.3% and 43.6%. The aim of this study is to determine the frequency of RAS mutations in patients with MCRC in Central America and the Caribbean. Methods: This is a retrospective-descriptive analysis of RAS mutations performed in patients with MCRC in Central America and the Caribbean. An informed consent was required for the mutational analysis. The information obtained has been kept in an anonymized database. Results: 2,138 tissue samples were analyzed by real time PCR. RAS mutations were documented in 46.7% of the cases, of these 94.8% correspond to mutations in kRAS and 5.2% to mutations in nRAS. 67.5% of RAS mutations were found in codon 12, 21.3% in codon 13, 5.8% in codon 146 and 4% in codon 61. 51.5% of the mutations were in males and 48.5% in females. RAS mutations in central american population were identified in a 45.8% and in a 42.5% in the caribbean. Conclusions: This is the first report of RAS mutations in patients with MCRC in Central America and the Caribbean. Our findings are similar to the data reported in other regions of the world. A clinical and epidemiological analysis and correlation of these findings is underway.
Cancer differentiation analysis technology as a novel technology for cerebral cancer screening.
Authors: Hongmei Tao, Xing Tang, Yue Lin, Chris Chang Yu, Xuedong Du
Journal: Journal of Clinical Oncology (2019)

2040 Background: While the current cancer screening methods mostly failed to detect cerebral cancer, a novel, promising technology named cancer differentiation analysis (CDA) technology has been developed to measure novel bio-physical properties to obtain valuable multi-level and multi-parameter information including protein, cellular and molecular level information. Initial results showed that CDA technology is capable of detecting cerebral cancer with a high degree of sensitivity and specificity. Methods: In this study, samples from 78 cerebral cancer patients and 321 healthy individuals were measured. Peripheral blood of each individual was drawn in EDTA tubes. One class of bio-physical property in blood samples was utilized for CDA tests. CDA data were conducted using SPSS, and the results were shown in table. Results: The average CDA values of cerebral cancer and control groups were 52.30 and 33.38 (rel. units) respectively. The results indicated that cerebral cancer could be significantly distinguished from the control (p &lt; 0.001). Area under ROC curve (AUC) was 0.980, and sensitivity and specificity was 92.3% and 96.6% respectively. Conclusions: Initial results showed that CDA technology could effectively distinguish cerebral cancer from healthy individuals. As a novel bio-physical based cancer detection approach with multi-level and multi-parameter expressions, CDA could be a potential candidate for cerebral cancer screening. Results from Statistical Analysis of CDA. [Table: see text]
Methylation and mRNA analysis of differential genes between primary tumor and liver metastasis in pancreatic neuroendocrine neoplasm.
Authors: Mengyu Feng, Jiangdong Qiu, Zhe Cao, Gang Yang, Yueze Liu, Taiping Zhang
Journal: Journal of Clinical Oncology (2019)

e15689 Background: The liver metastasis of pNEN is rare, and the underlying mechanisms remain unclear. The objective of this study is to compare the DNA methylation status and mRNA expression between primary tumor and liver metastasis in pNEN, aiming to find the potential gene responsible for liver metastasis in pNEN. Methods: The liver metastasis of pNEN is rare, and the underlying mechanisms remain unclear. The objective of this study is to compare the DNA methylation status and mRNA expression between primary tumor and liver metastasis in pNEN, aiming to find the potential genes responsible for liver metastasis in pNEN. Results: The differential methylation counts in the two patients were 17756 and 214321 respectively, indicating 1975 and 26176 differential genes (|diff.Beta| &gt; 0.14, at least one sample FPKM &gt; 0). mRAN analysis revealed 1302 and 3729 differential mRNAs (|log 2 fold change| &gt; 1, Q value &lt; 0.05). When combining these results together, 106 and 1513 genes were discovered, and the two patients had 39 differential genes in common. 13 genes with high mutation frequency in pNEN and 52 relevant pathways were selected in literatures. Among the 39 genes, only four genes were involved in these pathways: GREM1, PAX5, CLDN11 and FGFR2. However, only FGFR2 had both decreased methylation and increased mRNA expression in the two patients, and pyrosequencing confirmed that methylation position in FGFR2 was in accordance with results from methylation microarrays. Conclusions: The present study reveals that the gene expression varies greatly between primary tumor and liver metastasis in pNEN. The decreased methylation and increased mRNA expression of FGFR2 may play an important role in liver metastasis and further mechanisms are worthy of exploring.
The use of liquid and tissue biopsy genomic testing in lung cancer: A single-institution experience.
Authors: Natalia Marina, Tien Phuc Do, Praveen Namireddy, Nitika Sharma, Cynthia R. Cherry, Teresa Parent, Mark Bowling, Paul R. Walker
Journal: Journal of Clinical Oncology (2019)

e20692 Background: Liquid biopsy is an evolving minimally invasive technique to detect cell-free DNA (cfDNA) and cfRNA mutations by next generation sequencing (NGS) in plasma. In our Thoracic Oncology Program, we compared plasma liquid biopsy and tissue-based NGS assay results. Methods: Circulogene Theranostics Personalized Gene Profile (CGP), a 50-gene plasma NGS panel with proprietary direct-on-specimen enrichment technology, and tissue Caris Molecular Intelligence (CMI) NGS cfDNA and cfRNA including microsatellite instability (MSI)/microsatellite stability (MSS) and total mutational burden (TMB) results were retrospectively compiled and compared upon diagnosis. Results: 106 non-surgical lung cancer patients (median age 65 years, range 27-88; 66 men, 40 women) underwent CGP testing. 49 patients had sufficient tissue for comparative CMI. MSI detected in 20.4% (10/49) by CGP; no tissue MSI was found by CMI (0/44). 3 out of 4 (75%) MSI detected by CGP had high TMB ≥ 10 mut/Mb by CMI. 75% MSS patients by CGP had low TMB (12/16). Comparative plasma versus tissue mutations findings: TP53 mutations 60.3% (64/106) CGP and 69.3% (34/49) CMI. CGP TP53 mutated patients, high TMB 70.5 % (20/34) by CMI; EGFR mutations 13.2% (14/106) CGP and 14.2% (7/49) CMI; KRAS mutations 2.8 % (3/106) by CGP versus 28.5% (19/49); one ROS1 by CGP missed by CMI and one ALK by CGP insufficient tissue CMI. A higher frequency of BRAF 16.9% (18/106), PIK3CA 28.3% (30/106), PTEN 22.6% (24/106), and MET 7.5% (8/106) alterations was identified by plasma/CGP than comparative tissue/CMI 6.1% (3/49), 2% (1/49), 6.1% (3/49), and 0% (0/49) respectively. Conclusions: Our findings indicate that Circulogene liquid biopsy NGS detected common mutations, including actionable variants in lung cancer, providing expanded and complementary tumor molecular biology and therapeutic information to tissue NGS.
Treatment delays in localized breast cancer: A NCDB analysis.
Authors: Shruti Bhandari, Phuong Ngo, Sarah Mudra, Drew Carl Drennan Murray, Rachana Shirish Lele, Sudhir Srivastava, Xiaoyong Wu, Shesh Rai, Mounika Mandadi, Elizabeth Carloss Riley
Journal: Journal of Clinical Oncology (2019)

e18023 Background: Breast cancer remains the second leading cause of cancer death despite continued advances. Delayed treatment results in worse outcomes. Association with treatment location and trend over time are not well described. Methods: National Cancer Database identified 1042844 stage I-III breast cancer patients treated from 2004 - 2014. Multivariable analysis identified clinical and socioeconomic factors associated with delayed treatment and overall survival (OS). Results: Patients had a median age of 61y and a median time to treatment of 25 days. Time to treatment was ≤30d in 50.9%, 31 - 60d in 35.9%, 61 - 90d in 8.7% and &gt; 90d in 4.5% of patients. Percentage of patients with delayed treatment increased from 2004 to 2014 (For 61 - 90d: 6% to 10.6% and &gt; 90d: 3.3% to 5.1%). Multivariable analysis showed younger age, black race, no insurance/Medicaid, a higher comorbidity score, and later stage disease were significantly associated with treatment delay [Table]. OS was significantly worse with delayed treatment (HR: 1.11; 95% CI 1.08 - 1.13; p &lt; 0.001). Treatment at an academic facility was associated with treatment delays, however OS was better compared to community facility (HR: 0.81; 95% CI 0.79 - 0.82; p &lt; 0.001). Conclusions: Treatment delays of &gt; 90 days were rare but associated with worse OS. Despite the small percentages overall, this study shows an increase in treatment delays over the last 10 years. Academic centers were associated with treatment delays, but the OS was improved compared to other locations. Historic risk factors to timely treatment were again identified, despite increased efforts to reduce disparities. Further analysis of practice patterns is needed to better understand the direct clinical impact of these findings, especially in vulnerable populations. [Table: see text]