tbuckley/cabot-search huggingface dataset:
Impact of non-compliance with guidelines in early type 1 endometrial cancers management, study from FRANCOGYN group.
Authors: Hélène Costaz, Sofiane Bendifallah, Emilie Raimond, Clémentine Jankowski, Sabrina Dridi, Vincent Lavoué, Pierre Collinet, Lobna Ouldamer, Cyril Touboul, Alexandre Bricou, Marie-Martine Padeano, Catherine Loustalot, Olivier Graesslin, Marcos Ballester, Charles Coutant
Journal: Journal of Clinical Oncology (2019)

5587 Background: To standardize surgical practices, ESMO-ESGO-ESTRO consensus conference published in 2016 new guidelines on the management of endometrial cancer. The main objective of this study was to evaluate the impact of non-compliance with current surgical guidelines on disease-free survival and overall survival. Methods: 852 patients with presumptive stage I and II type 1 endometrial cancer were included in a multicenter retrospective study, conducted between January 2000 and November 2015. The main objective of this study was to evaluate the impact of non-compliance with current surgical recommendations on overall survival and disease-free survival. Results: Our study shows that 34.3% of patients (n = 292) did not benefit from optimal surgical treatment. These patients did not have a lombo-aortic lymphadenectomy (LAL) and were at high risk of recurrence. There is a significant difference in disease-free survival in favor of patients undergoing surgery according to the recommendations, (Hazard Ratio (HR): 0.37 (Confidence interval (95% CI): 0.26-0.54), p &lt; 0.001). In multivariate analysis, optimal surgical procedure performance is an independent factor for disease-free survival with HR at 2.04 (95% CI: 1.14-3.68), p = 0.01. There is a significant difference in overall survival in favor of patients undergoing surgery according to the recommendations, (HR: 0.31 (95% CI): 0.19-0.49), p &lt; 0.001. In multivariate analysis, there is a trend toward significance with HR: 2.24 (95% CI: 1-5.05), p = 0.05. Older patients, patients with a larger BMI, patients with no indication of LAL at the preoperative ESMO classification, and no node involvement in are factors contributing to the decision of not to perform a LAL: p &lt; 0.001, p = 0.03, p &lt; 0.001 and p &lt; 0.001 respectively. Conclusions: This study shows that patients with early type 1 endometrial cancer have improved recurrence-free survival and a statistical trend for an increased overall survival when recommended surgery is performed. Despite the current context of therapeutic de-escalation, we must strive to achieve the recommended optimal surgery, even if it requires secondary surgical revision, to avoid underestimation of patients with a poorer prognosis. To improve endometrial cancers management, amelioration of the preoperative assessment by increasing the sensitivity of emboli detection should be considered.
A novel approach to support community oncology practices in building a clinical research program.
Authors: Jeremy Miller, Debra A. Kientop, Linda Andrews, William Jeffery Edenfield, David Hadley
Journal: Journal of Clinical Oncology (2019)

e18087 Background: Starting a clinical research program in a community oncology setting has a myriad of challenges. While ASCO provides guidance through its “Basic Requirements for Starting a Research Practice”, building a research program requires significant time and effort. We present an example of how a technology-enabled solution supports a consortium of community oncology practices to rapidly grow their clinical research program, as they strive to meet the Commission on Cancer goal of &gt; 4% clinical trial enrollment. Methods: Four key pillars that support a successful research program include: building program infrastructure, establishing standard operating procedures, engaging patients and accessing clinical trials. The consortium receives support for each of these components through a combination of software tools and professional services. Results: The practices in the consortium currently have clinical trial enrollment that is less than desired, but the number of patients on clinical trials in the consortium for coming year is expected to grow between two and ten-fold. The table below shows the enrollment by site in 2018 for the 7 practices that have been engaged for the full year. Candidates are patients who have found to be eligible for at least one clinical trial, but have not yet been enrolled or declined. Conclusions: The practices have been engaged in the consortium for approximately one year. While some practices are well below their eventual target of 4% enrollement, the increasing number of patients screened, and their growing clinical trial portfolio of well-matched clinical trials has them well on their way to that target over the next two years.[Table: see text]
Case 28-1988
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Thomas J. Hougen, James F. Southern
Journal: New England Journal of Medicine (1988)

Presentation of CaseA 17-year-old girl was admitted to the hospital because of dyspnea and chest pain.The patient was well until one year earlier, when she began to experience increasing fatigue, exertional dyspnea and chest pain, and palpitations. She occasionally awoke during the night with dyspnea. During the several weeks before entry the fatigue and exertional dyspnea and chest pain worsened, and she became unable to climb one flight of stairs without pausing to rest. She was admitted to the hospital.The patient was a native of Africa, who immigrated to this country four months before entry and spoke . . .
Impact of international collaboration utilizing E-consult and E-tumor board in the multidisciplinary management of cancer patients: A study from Mayo Clinic Care Network (MCCN) members.
Authors: Faraz A. Khan, Saima Maqbool, Maroun Elkhoury, Thomas Matthew Habermann, Tariq Dufan, Abdul Hafeez Siddiqi, Aaron Han, Kadriya Sayed, Yasin Ahmed, Karthikh Kantawala, Mahmood Hamza, Arjuna Sonal, Salima Ahmed, Carolyn Yang, Dunia Abdelrahman
Journal: Journal of Clinical Oncology (2019)

e18261 Background: Multidisciplinary tumor board meetings have shown to improve quality and outcome in the care of cancer patients. Many tertiary centers conduct site specific tumor board meetings but not all the centers especially community oncology and international centers have the manpower capacity to hold site specific meetings, the overall impact of tumor boards on patients care may vary based on its structure and composition. We propose that institutional collaboration in the comprehensive care of cancer patients utilizing E-consult and E tumor board may help to improve patient care. Methods: Retrospective data of 134 patient cases seen at the American hospital Dubai between 2016-2018 was analyzed. Cases that were reviewed at the American Hospital multidisciplinary tumor board meeting (AHD-MDT) and also referred for second opinion utilizing Mayo e-consult/e-tumor board service were analyzed using electronic health record, AHD-MDT meeting minutes and reports of Mayo e-consult/e-tumor board. 3 major areas of case assessment for review were selected 1. Pathology . 2. Medical imaging. 3. Clinical recommendations. Variation in assessment and recommendations between AHD- MDT and Mayo Clinic were compared. Results: A total of 1018 cases were reviewed in the AHD-MDT between 2016 and 2018. 136 out of the 1018(13%) cases were referred for second opinion utilizing Mayo E-Consult or E-tumor board service. 117 cases were included in the analysis as there was missing data in 4 patients, 9 were duplicate and 4 were cancelled and 7 cases were not reviewed at AHD-MDT. In 78 cases pathology was reviewed at Mayo but 4 (5%) were not reviewed at AHD. In 74 (95%) cases, pathology was reviewed both at AHD and Mayo. There was change (Ch) in 2 (3%), 7(9%)updated(Ud) and no change(Ch) in 65 cases(88%). 97 cases of imaging had change(Ch) in 1 case (1%). 101 cases of e-consult/e-tumor board were assessed for clinical recommendations. There was change(Ch) in 3(3%), 2/3 cases had a change in plan due to change in the pathology. In 35(35%) the plan was updated (Ud) and 7 out of 35(20%) were due to updated(Ud) pathology. Conclusions: Our data indicates that international collaboration as part of MCCN has resulted in significant improvement in the patient care. In a select group of challenging cases, 35% had an improvement in the final treatment plan after utilization of e-consult/e-tumor board service.
Building international partnerships to improve global oncological care: Perspective from Rutgers-CINJ Global Oncology Fellowship Program.
Authors: Ashwin Chandar, Sukhdeep Kaur, Deborah Toppmeyer, Tlotlo Bathethi Ralefala, Roger Strair, Claire Philipp, Richard Marlink, Reena Antony, Marilyn DiGiacobbe, Refeletswe Lebelonyane, Tendani Gaolathe, Tina M. Mayer
Journal: Journal of Clinical Oncology (2019)

e18161 Background: With cancer accounting for 1 in every 7 deaths worldwide and 60-70% of cancer deaths occurring in low- and middle-income countries, any advancement in cancer care should include understanding to alleviate structural inequalities that produce these global oncologic disparities. Rutgers-Cancer Institute of New Jersey (R-CINJ) Oncology Fellowship program, through partnerships with Rutgers Global Health and University of Botswana (UB), established a global oncology program in 2018 to provide young oncologists in training with this educational opportunity. Aims included understanding challenges faced by cancer patients in Botswana, evaluating opportunities to improve oncology care at Princess Marina Hospital (PMH), scholarly collaborations, and exchange knowledge. Methods: In partnership with PMH, UB, and Ministry of Health and Wellness (MOHW), R-CINJ created a global oncology program consisting of a 1 month rotation at PMH in Gaborone, Botswana, as well as longitudinal research/quality improvement (QI) projects. Two 3rd year oncology fellows rotated with house officers and oncologist at PMH. Weekly video conferences facilitated communication during the elective. Projects continued throughout 3rd year of fellowship, in conjunction with programmatic meetings. Results: Fellows gained exposure to cancer care using limited resources. In working with PMH staff, mentorship was provided, QI ideas were shared, and organizational changes were implemented. Scholarly activity was undertaken to examine trends in chemotherapy utilization at PMH over a 12-month period to assess patterns of malignancy and issues with stock outs. Relationship between pathology at PMH, UB, R-CINJ, and Rutgers Biomedical Engineering was established to expand digital pathology services in Botswana. Conclusions: Our global oncology program is a successful start to an ongoing partnership to help improve cancer care in Botswana. Future directions include development of cancer guidelines and protocols in Botswana, helping limit medication shortages, and establishing telemedicine based collaboration to assist with diagnosis and improve pathology turnaround time.
Integrated genomics-based approach to identify new therapeutic targets and cancer biomarkers for lung cancer.
Authors: Yataro Daigo, Atsushi Takano, Yusuke Nakamura
Journal: Journal of Clinical Oncology (2019)

e13019 Background: Because the number of lung cancer patients who show good response to standard therapies is still limited, development of new anti-cancer agents with minimum risk of adverse effects and highly sensitive molecular biomarkers is urgently required. Methods: We have been screening novel therapeutic targets and their companion biomarkers for lung cancer as follows; i) To identify up-regulated genes in lung cancers by the gene microarray analysis, ii) To verify the candidate genes for their low expression in normal organs, iii) To validate the clinicopathological significance of their protein expression by tissue microarray covering hundreds of lung cancers, and iv) To verify their function for the growth of lung cancer cells by siRNAs. Results: We identified dozens of candidate oncoproteins and selected a serine/threonine kinase LASK2 (lung cancer-associated kinase 2). Immunohistochemical analysis showed that strong LASK2 positivity was an independent prognostic factor for non-small cell lung cancer patients (P &lt; 0.0001). Suppression of LASK2 expression by its siRNAs inhibited proliferation of lung cancer cells. Introduction of LASK2 in mammalian cells also enhanced cellular growth in vitro and in mice model. Induction of LASK2 appeared to increase the levels of phosphorylation of oncogenic signal proteins for lung cancer. The data indicate that LASK2 is a prognostic biomarker and therapeutic target for lung cancers. Conclusions: Integrated genomics-based approach could facilitate the development of new cancer biomarkers as well as therapeutic targets for small molecules, monoclonal antibodies, nucleic acid drugs, and immunotherapies.
Case 46-1986
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Judith L. Vaitukaitis, Robert E. Scully
Journal: New England Journal of Medicine (1986)

Presentation of CaseA 26-year-old woman was admitted to the hospital because of secondary amenorrhea.Her menarche occurred at the age of 14 years, when her weight was 50.9 kg and her height 160 cm. Her first two menses were irregular, but subsequent menstrual periods were regular and consisted of 5 days of flow, with a 35-day menstrual interval. Most of her menses were preceded by a mild backache and increased appetite, without bloating or breast tenderness. The patient began sexual activity at the age of 18 years and used a diaphragm and a spermicidal jelly. At the age of . . .
Study of the clinical characteristics of scrotal mesothelioma.
Authors: Chen Zhang, Harry Jack Goldsztajn
Journal: Journal of Clinical Oncology (2019)

e16122 Background: Scrotal mesothelioma (SM) is an extremely rare type of genitourinary cancer. To the best of our knowledge, no clinical trial was performed in SM. The objective of this study aims at evaluating the clinical characteristics of scrotal mesothelioma. Methods: Retrospective and comprehensive literature search was performed for SM case report/series on PUBMED/Medline. 184 articles were found through January 2019 and 81 articles were excluded due to non-English language or unavailability. A total of 124 patients in 103 articles were included. All necessary data were extracted including age, asbestos exposure history, clinical presentation, diagnostic method, tumor marker, management approach and surveillance. P &lt; 0.05 was considered significant. Results: Out of 124 patients, the median age at diagnosis was 60 years old. 16 patients (12.9%) had a history of asbestos exposure, 58 (46.8%) without exposure and 50 (40.3%) were not mentioned. Most common initial presentation was hydrocele (n = 78, 62.9%), followed by mass (n = 38, 30.6%). 50% (n = 62) of tumors presented on the right testicle while 34.7% (n = 43) were on left side, 0.8% (n = 1) bilaterally and 14.5%(n = 18) were unclear. 40 (32.3%) patients developed metastatic disease, while 20 (16.1%) developed it at diagnosis. 102 (82.3%) patients were diagnosed by post-operative pathology, and 22 (26.7%) were diagnosed before surgery. Alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) were checked in 24 patients. AFP was uniformly negative (100%) and hCG was negative in 23 patients (95.8%). Most patients underwent surgery (n = 119, 96%), of which orchiectomy and/or hemiscrotectomy (n = 93, 78.2%) comprised the majority. For adjuvant therapy, 14 (11.3%) patients received radiotherapy and 9 (7.3%) received chemotherapy. Out of 71 patients without initial metastasis and with follow-up data, median follow-up time was 17 months, median time to recurrence was 19 months, and 5-year recurrence-free status was 11.3%. Conclusions: The most common presentation of SM is hydrocele and the most common location is the right testicle. Surgery is a common intervention, but the recurrence rate is high. Due to limited number of reports, more clinical data and further clinical studies are warranted for management guidance.
An open label, multicenter, phase II study of KRT-232, an oral small molecule inhibitor of MDM2, for the treatment of patients with Merkel cell carcinoma (MCC) who have failed treatment with anti-PD-1/L1 immunotherapy.
Authors: Glenn J. Hanna, James A. DeCaprio, John Hai Ming Mei, Jesse S. McGreivy
Journal: Journal of Clinical Oncology (2019)

TPS9602 Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a poor prognosis in patients with advanced disease, with mortality as high as 46%. An oncogenic Merkel cell polyomavirus (MCPyV) is present in about 80% of MCC tumors, which inactivates tumor suppressors p53 and RB. Virus-positive MCC has proven to be an immunologically responsive disease and the recently approved PD-L1 inhibitor avelumab (March 2017) has improved the prognosis of patients with advanced MCC. However, despite the addition of immune checkpoint inhibitors to the treatment paradigm, a lack of response or disease progression occurs in up to two-thirds of avelumab patients previously treated with chemotherapy, and 32-44% of first-line patients treated with the PD-1 inhibitors nivolumab or pembrolizumab. KRT-232 is a potent and selective small molecule targeted drug that binds to murine double minute chromosome 2 (MDM2) and inhibits the MDM2/tumor protein 53 (p53) protein-protein interaction. Inactivating mutations in p53 have rarely been found in MCC, and the majority of MCCs with the presence of MCPyV express p53 WT . The purpose of this study is to evaluate the tolerability and efficacy of KRT-232 in p53WT MCC patients who have been treated with anti-PD-1/L1 immunotherapy. Methods: The primary objective is ORR by RECIST v1.1 after 2 cycles (42 days) as determined by independent review. A Simon two-stage design is employed. In Stage 1, up to 13 eligible patients will be enrolled and treated with 240 mg KRT-232 once daily (QD) on Days 1-7 of a 21-day cycle. If the predesignated efficacy threshold is reached in Stage 1, enrollment for Stage 2 will include an additional 14 patients (for a total of 27 patients). The study is enrolling in the U.S. Clinical trial information: NCT03787602.
Impact of the route of nutrition on gut mucosa in ventilated adults with shock: an ancillary of the NUTRIREA-2 trial
Authors: Gaël Piton, Amélie Le Gouge, Noelle Brulé, Benoit Cypriani, Jean-Claude Lacherade, Saad Nseir, Jean-Paul Mira, Emmanuelle Mercier, Michel Sirodot, Jean-Philippe Rigaud, Stéphanie Malaquin, Edouard Soum, Michel Djibre, Stéphane Gaudry, Didier Thévenin, Jean Reignier
Journal: Intensive Care Medicine (2019)
Risk stratification based on a prognostic factor index among patients with HR+, HER2- MBC.
Authors: Gregory A. Vidal, Gebra Cuyun Carter, Adrienne Gilligan, Kim Saverno, Yajun Emily Zhu, Gregory L Price, Angelo Deluca, Emily Nash Nash Smyth, Andrew G. Koustenis, Yujing Huang, Lee S. Schwartzberg
Journal: Journal of Clinical Oncology (2019)

e12516 Background: Patient and tumor characteristics, such as tumor grade (TG), site of metastases, hormone receptor status, and endocrine resistance, affect the prognosis for patients (pts) with HR+, HER2- metastatic breast cancer (MBC). This study explored the impact of multiple clinical prognostic factors on pt overall survival (OS) and real-world progression-free survival (rwPFS). Methods: This retrospective study used electronic health record (EHR) data of US pts from a network of community oncology practices maintained in the Vector Oncology Data Warehouse from 1/1/2008 to 4/30/2017. Eligibility included HR+, HER2- MBC diagnosis in 2008 or later and prior systemic therapy for MBC. An index variable was created to assess the effect of multiple clinical prognostic factors collectively, including liver metastases (LM), primary endocrine resistance (PER) (Cardoso F et al. 2018), negative progesterone receptor (PR-) status, and high TG. Pts were grouped based on the number of prognostic factors present at MBC diagnosis: 0, 1, and 2+. Differences in rwPFS and OS from start of first line therapy were evaluated by Kaplan-Meier method and multivariable Cox proportional hazards regression. Results: Eligible pts (n=378) had a mean age of 60.3 years. Among these 57.1% were white, 36.5% were de novo metastatic, 22% had LM, 27.2% had high TG, and 27.1% were PR- at baseline. Among all pts, 170 (45%) had received endocrine therapy as first-line treatment, followed by chemotherapy (28%), CDK4 &amp; 6 inhibitor (17%), or other anti-cancer treatment (9%). After adjustment, rwPFS and OS were significantly (p&lt;.05) shorter in pts with 1 and 2+ clinical prognostic factors compared to pts with none (Table). Conclusions: Among pts with HR+, HER2- MBC, these data demonstrate the heterogeneity in pt survival outcomes depending on the presence and number of prognostic factors. Further research should explore the collective importance of these prognostic factors in treatment decisions. [Table: see text]
Assessing treatment benefits with CDK4/6i+ET for hormone receptor-positive advanced breast cancer: A network meta-analysis.
Authors: Ramon Andrade De Mello, Pedro Nazareth Aguiar, Benjamin Haaland, Pui San Tan, Mariane Teodoro Fernandes, Ana Claudia Barbin Spinosa, Auro Del Giglio, Gilberto Lopes
Journal: Journal of Clinical Oncology (2019)

e12543 Background: Previously, the treatment of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (aBC) has relied solely on endocrine therapy (ET). Unfortunately, almost all tumors developed resistance to ET. Although cyclin-dependent kinase inhibitors (CDKi)+ET clearly improve several clinical outcomes, many relevant questions remain unanswered: is there a benefit in (i) overall survival (OS) (ii) progression-free survival (PFS), and (iii) which CDKi is the best. Methods: A systematic review was performed to identify trials that compared CDKi+ET versus ET alone for HR+/HER2-aBC. Pooled meta-estimates were generated to assess CDKi+ET OS benefit and PFS benefit. Bayesian network meta-analysis was performed to compare each CDKi in terms of PFS, clinical benefit rate (CBR), response rate (RR) and toxicity. Results: 2,523 studies were screened and 8 studies satisfied the inclusion criteria. There was a trend for OS benefit with CDKi+ET compared to ET alone with 97% posterior probability that CDKi+ET is better than ET alone and HR 0.81 (95% CrI 0.66-1.00). CDKi+ET also showed &gt; 99% probability of better than ET alone in both first and second-line settings in terms of PFS, RR, and CBR with PFS HR 0.56 (0.47-0.66) first line, 0.49 (0.39-0.60) second-line; RR OR 1.61 (1.29-1.97) first-line, 2.58 (1.71-3.80) second-line; CBR OR 1.75 (1.38-2.25) first-line, 2.38 (1.65-3.37) second-line. Ribociclib and abemaciclib showed weak-moderate evidence of better PFS and RR compared to palbociclib (64% to 81% posterior probability of superiority). There was no evidence of differences between ribociclib and abemaciclib. Palbociclib achieved better CBR compared to ribociclib and abemaciclib, although this difference may be related to the poor performance of placebo arm in studies that used palbociclib. In terms of safety, abemaciclib caused less neutropenia, but more diarrhea than ribociclib and palbociclib. Deep vein thrombosis was less frequent with ribociclib. Conclusions: CDKi+ET was 97% superior in terms of OS and &gt; 99% superior in terms of PFS, RR, and CBR compared to ET alone. Further studies are necessary in order to find the best agent and the best sequencing of CDKi for HR+/HER2- aBC treatment.