tbuckley/cabot-search huggingface dataset:
Toward early diagnosis decision support for breast cancer: Ontology-based semantic interoperability.
Authors: Mengchun Gong, Zhi Wang, Yefu Liu, Hong Zhou, Fang Wang, Yishang Wang, Na Hong
Journal: Journal of Clinical Oncology (2019)

e18072 Background: Breast cancer is ranked as the most common cancer among women in China, cases in China account for about 300,000 of all newly diagnosed breast cancers each year. Developing Clinical Decision Supporting System (CDSS) to assist early diagnosis breast cancer is valuable, however, lack of semantic interoperability in CDSS has been identified as the main obstacle for broad adoption of CDSS. Ontology is considered to be one of the effective approaches to bridge the terminology gap between various clinical systems and data sources. In this study, we describe our efforts in transforming breast cancer clinical knowledge into computable ontology to support breast cancer early diagnosis. Methods: We have built a breast cancer ontology (BCO) to support our CDSS pipeline. A number of NCCN clinical practice guidelines in Oncology for Breast Cancer and the breast cancer diagnosis and treatment guidelines of China are the main knowledge sources of the BCO. BCO is a manually curated resource that contains concepts and relations of breast cancer clinical findings, demographics, laboratory tests, imaging results, treatments, pathologies, cancer stages, body structure and follow-up information. These curated knowledges are annotated through interoperable standard vocabulary SNOMED CT. Two physicians reviewed and evaluated the BCO. Results: Concepts in BCO currently contains 79 clinical findings, 8 demographics, 42 laboratory tests, 105 imaging results, 332 treatments, 141 pathology and cancer stages, 30 body structures and 3 follow-ups. Relations are defined such as finding site, associated with, etc. The concepts hierarchies and relationships were built by using Protégé to support OWL representation. As an initial evaluation results, most of concepts could be mapped to SNOMED CT, but there are some concepts could not be exactly mapped to SNOMED CT. We created local Chinese Vocabularies for these local terms. Conclusions: Based on interoperable BCO, a group of computable rules are developed by adding statements according to early diagnosis criteria of breast cancer. Diagnosis assistance around complex patients is supported though connecting the Electronic Health Record (EHR). This is an ongoing development that the BCO is continuingly enriched with standard concepts, relations and integrate with individual instances to support broader adoptability.
Major lab abnormalities as biomarkers in patients treated with immune checkpoint inhibitors: A single institution study of 1044 patients.
Authors: Kai Laukamp, Joseph Liput, Daniel Arnold Smith, Ariel Ann Nelson, Nikhil H. Ramaiya, Christopher J. Hoimes
Journal: Journal of Clinical Oncology (2019)

e14108 Background: Over the past decade, immune checkpoint inhibitors (ICI) have gained increased importance in modern cancer treatment. In this study we investigate the relationship between major lab abnormalities and ICI treatment duration. Methods: 1044 patients receiving ICIs between 2010-2018 were included in this retrospective study. The following parameters were analyzed: gender, age, race, cancer type, lab abnormalities for kidneys, pancreas, liver and thyroid, and treatment duration. Lab abnormalities were grouped and used in a scoring-system (0: no lab abnormalities, 1: one abnormal parameter, and 2: two or more abnormal parameters). For statistical analysis, Likelihood Ratio Chi-Square and Mann-Whitney U tests were applied. Results: The patient cohort included 386 female and 473 male patients with a mean age of 67.8±12.5 years. Primary cancer distribution included lung cancer (n = 439), melanoma (n = 253), head and neck cancer (n = 72), renal cancer (n = 53), lymphoma (n = 33), bladder cancer (n = 42), breast cancer (n = 28), and other malignancies (n = 124). Patients received one (n = 875) or a combination (n = 169) of ICIs for a mean of 152.2±215.8 days, with highest counts for nivolumab (n = 465), pembrolizumab (n = 275), ipilimumab (n = 95), and nivolumab &amp; ipilimumab (n = 130) and others (n = 79). Patients with higher values in the scoring-system or more lab abnormalities had significantly longer treatment duration (Score 0: 107±170, 1: 159±199, 2: 244±282 days, p &lt; 0.001). Furthermore, patients treated with ICI combination therapy demonstrated higher scores (1.1±0.8 vs. 0.5±0.7, p &lt; 0.001) and longer treatment durations (236±304 vs. 127±175 days, p &lt; 0.001). Patients with scores of ≥1 in the scoring system had improved overall survival (451±475 vs. 369±526 days, p &lt; 0.001), and patients treated with two or more ICIs lived longer (563±524 vs. 377±496 days, p = 0.003). Therapy duration was also positively correlated with survival (Spearman’s rho correlation r = 0.64, p &lt; 0.001). Conclusions: Our current exploratory study demonstrates associations between major lab abnormalities and both treatment duration and overall survival in patients treated with immune checkpoint inhibitors.
Phase I study of fluzoparib, a PARP1 Inhibitor in combination with apatinib and paclitaxel in patients (pts) with advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Jian-Ming Xu, Rongrui Liu, Yi Ba, Da Jiang, Mingxia Wang, Yulong Zheng, Jia Wei, Yu-Xian Bai, Lizhu Lin, Jianping Xiong, Xixi Zhu, Chuanhua Zhao, Ru Jia, Yun Zhang, Jianzhi Liu, Gairong Zhang, Guangze Li, Quanren Wang
Journal: Journal of Clinical Oncology (2019)

4060 Background: Fluzoparib (SHR3162) is an oral, selective PARP1 inhibitor. In our gastric cancer PDX model, fluzoparib + apatinib + paclitaxel demonstrated significant tumor growth inhibition as compared to apatinib alone, and fluzoparib + paclitaxel. In this phase I study, we hypothesized that the combination of fluzoparib+apatinib+paclitaxel should be safe and active in pts with advanced gastric and GEJ cancer. Methods: Dose-escalation phase (P1) explored 4 dose levels of fluzoparib with a 3+3 design to identify a recommended phase II dose (RP2D) for further study. Pts received fluzoparib (20, 30, 40, 60 mg/twice daily)+apatinib (250mg/day)+paclitaxel (60mg/m2, Day1, 8, 15). Dose-expansion phase (P2) was to assess safety and efficacy. Pts received RP2D of fluzoparib+apatinib+paclitaxel until progression or intolerant toxicity. Treatment was repeated every 4 weeks. Pts had to have progressive disease after standard platinum-based regimen treatment. Adverse events (AE), PK, and response per RECIST 1.1 (every 8 wks in pts with measurable disease) were assessed. Results: 39 pts (median age 58) have been treated in P1 and P2, including fluzoparib 20mg (n=4), 30mg (n=27; 6 pts in P1, 21 pts in P2), 40mg (n=6), and 60mg (n=2). The median treatment duration for this study was 2.8 months. No DLTs were reported in 20mg cohort. One DLT occurred in 30 mg cohort (grade 3 [G3] hypophosphatemia), 1 DLTs (1 grade 4 [G4] febrile neutropenia) occurred and 1 G4 neutropenia occurred and recovered in 3 days in 40mg cohort, 2 DLTs (1 G4 neutropenia, 1 G4 febrile neutropenia) in 60mg cohort. Therefore, 40 mg dose was deemed the MTD. There were no treatment-related deaths on study. The most common AEs≥G3 were neutropenia, febrile neutropenia, and hypertension. 1 treatment-related discontinuation was observed. Of 36 evaluable pts, 12 (30.0%) had confirmed partial response and 13 had stable disease (36.1%). Median progression-free survival was 4.9 months. PK analysis will be presented. Conclusions: The RP2D of combination of fluzoparib + apatinib + paclitaxel is well tolerated and has activity in pts with advanced gastric and EGJ cancer who have failed to platinum-based regimen. Clinical trial information: NCT 03026881.
Fear of receiving less effective care: A barrier to effective cancer care cost communication.
Authors: Sokbom Kang, Yelee Yu
Journal: Journal of Clinical Oncology (2019)

e18339 Background: Increasing financial burden in cancer care promoted cost communication as an intervention to the problem. We explored patients’ attitudes and concerns for the physician-patient communication of the costs of cancer care. Methods: From an oncology outpatient clinic, patients were recruited and interviewed using a 29-item questionnaire. The questionnaire includes basic and financial characteristics, attitudes toward cost-communication, and experience of cost-communication with oncologists. Results: Among 292 patients with gynecologic cancer, 68% were found to have an income below the nation’s average households income. Although the majority (81%) of patients have a positive attitude toward patient-physician cancer care cost-communication, however, only 19% of them wanted to discuss the cost with their physicians - 33% of them did not want to disclose their financial status to health care providers and 48% wanted to discuss the cost with other providers than their physicians. In addition, while 87% preferred to be informed about costs for various treatment options, 86% of them did not want to receive cost-effective treatment and preferred to receive the most effective treatment regardless of their financial status. Compared with non-cancer patients (n = 83), significantly more patients had a negative attitude to disclosing their financial status especially to their physician (22% vs. 11%, P = 0.024). Conclusions: A considerable proportion of cancer patients had concerns that cost communication with their physician may interfere with their opportunity to access the best care options. To facilitate cost communication, oncologists should understand such concerns and making a thoughtful effort to relieve the concern during cost communication.
3D in vitro system for measuring treatment responses to immunotherapy in CRC patients.
Authors: Andreas Block, Hauke Stamm, Tamara Sutus Temovski, Leonie Konczalla, Franziska Brauneck, Inke Stange, Sandra Koellmann, Jun Li, Daniel R. Perez, Jacob Thastrup, Jasmin Wellbrock, Walter M. Fiedler, Juergen Kupper, Tabea Sturmheit
Journal: Journal of Clinical Oncology (2019)

e15114 Background: Current clinical guidelines for the treatment of cancer patients mainly rely on intrinsic characteristics of a given tumor, such as its localization, its staging and in some instances also known genetic markers. The success of treatment administered according to this proceeding is, however, undermined by large inter-individual variability of tumors. Embedded in a unique meshwork of extracellular matrix, stromal cell and bioactive factors, malignant cells accumulate a distinctive pattern of genetic, epigenetic and metabolic alterations, resulting in unrestricted growth. Despite the potential availability of tailored drugs, matching cancer drug therapy to the unique characteristics of a patient’s tumor, is generally unfeasible in clinical practice. Methods: Addressing this need, 2cureX developed a functional test (IndiTreat) for measuring the responsiveness of micro-tumors (tumoroids) derived from colorectal cancer (CRC) and liver metastases to chemotherapeutic agents, targeted therapies and combinations thereof. To further broaden the applicability of the IndiTreat test, the present study aims to adapt the assay system to functional testing of immunotherapeutics. The success of immunotherapeutic treatment (I/O) regimens is currently limited to a small subset of CRC patients such as those with microsatellite instability (MSI) high tumors. However, new chemo-immunotherapies may prove beneficial for a greater percentage of patients. Results: To pre-therapeutically assess the potential efficacy of I/O interventions for individual patients, we co-culture tumoroids and autologous PBMCs and monitor immune-mediated killing of tumoroids in vitro. Subsequently, these culture systems will be tested regarding their susceptibility towards an array of single or combined I/O drugs. Tumoroids recapitulate the highly individual disease of cancer patients and, as demonstrated by our allogenic setting, constitute a valuable platform for testing different aspects of immune-mediated tumor cell recognition and killing. Conclusions: In light of an increasing number of cost-intensive I/O treatment options becoming available to CRC patients, pre-therapeutic testing of individual responses to immunotherapy will be of key relevance in assisting the oncologist to select the most potent treatment regime for every patient available.
Lack of Ability to Present Antigens on Major Histocompatibility Complex Class II Molecules Aggravates Atherosclerosis in ApoE <sup>−/−</sup> Mice
Authors: Maria Wigren, Sara Rattik, Ingrid Yao Mattisson, Lukas Tomas, Caitriona Grönberg, Ingrid Söderberg, Ragnar Alm, Lena Sundius, Irena Ljungcrantz, Harry Björkbacka, Gunilla Nordin Fredrikson, Jan Nilsson
Journal: Circulation (2019)

Background: Hypercholesterolemic mice lacking factors required for activation of CD4 + T cells are characterized by reduced development of atherosclerosis. Consequently, it has been assumed that atherosclerosis involves loss of tolerance against modified self-antigens generated in response to hypercholesterolemia and that presentation of such antigens on major histocompatibility complex class II (MHCII) leads to activation of proatherogenic Th1 cells. In this study, we wanted to determine the role of antigen presentation on MHCII in atherosclerosis development. Methods: Apolipoprotein E (ApoE −/− ) mice deficient for MHCII (ApoE −/− MHCII −/− ) were used to study the role of MHCII in atherosclerosis development. Results: Compared with ApoE −/− mice, ApoE −/− MHCII −/− mice had reduced levels of CD4 + T cells, immunoglobulin G and M levels, and Th1 and Th2 cytokines in plasma. CD8 + T cells were increased and regulatory T cells were reduced both in spleen and in lesions of ApoE −/− MHCII −/− mice. Decreased plasma levels of inflammatory cytokines in ApoE −/− MHCII −/− mice indicated reduced systemic inflammation. Despite this, ApoE −/− MHCII −/− mice had significantly more atherosclerosis as assessed by en face Oil Red O staining of the aorta (4.7±2.9% versus 1.9±1.3%; P &lt;0.01) and cross-sectional area of subvalvular lesions (7.7±2.2×10 5 µm 2 versus 4.6±2.8×10 5 µm 2 ; P &lt;0.05). Cell transfer and blocking antibody studies suggested that loss of regulatory T cells is the most important cause of aggravated atherosclerosis in ApoE −/− MHCII −/− mice. Conclusions: Our observations demonstrate that antigen presentation on MHCII has important protective functions in atherosclerosis and that this is primarily the result of activation of regulatory T cells. These findings have implications for understanding the possible risks and benefits of immunosuppressive therapy in patients with cardiovascular disease.
Mismatch repair deficiency as a predictor of adjuvant radiotherapy response in endometrioid endometrial carcinoma.
Authors: Stefan Kommoss, Casper Reijnen, Heidi V.N. Küsters-Vandevelde, Clemens Prinsen, Massuger Leon, Marc P.M.L. Snijders, Sara Brucker, Diethelm Wallwiener, Janice S Kwon, Jessica N. McAlpine, Johanna M.A. Pijnenborg
Journal: Journal of Clinical Oncology (2019)

5586 Background: Adjuvant radiotherapy improves progression-free survival in intermediate and high-risk endometrial cancer. However, so far there is no evidence of improved overall or disease-specific survival after adjuvant radiotherapy. There is accumulating evidence that MMR proteins are involved in DNA repair following radiotherapy. We investigated the predictive value of MMR status in terms of survival benefit after adjuvant radiotherapy in patients with stage IB/II, grade 3 endometrioid endometrial cancer (EEC). Methods: A retrospective multicenter cohort study was performed to compare patients with histopathologically confirmed stage IB/II grade 3 EEC with and without adjuvant radiotherapy. Patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identifying ECs as either MMR-deficient, POLE, p53abn or p53wt. Multivariable Cox regression analysis explored associations between patient characteristics, adjuvant treatment and outcome. Results: A total of 128 patients were analyzed, including 57 patients (43.0%) with MMR-deficient EECs. Baseline characteristics were comparable, except a higher proportion of MMR-deficient EECs were stage II (36.8% vs. 15.5%, p = 0.006). Eighty-two patients (64.1%) received adjuvant radiotherapy (external beam [n = 55], vaginal brachytherapy [n = 27]). In multivariate analysis, adjuvant radiotherapy was independently associated with improved disease-specific survival in patients with MMR-deficient EECs (hazard ratio 0.19, 95%-CI 0.05 - 0.77), but not in patients with MMR-proficient EECs (hazard ratio 0.92, 95%-CI 0.37 - 2.31). Conclusions: Adjuvant radiotherapy improved disease-specific survival in patients with MMR-deficient EECs, but not in those with MMR-proficient EECs. This study demonstrates the predictive ability of MMR IHC to identify women who likely have increased benefit from radiotherapy.
Improving cascade genetic testing for families with inherited pancreatic cancer (PDAC) risk: The GENetic Education, Risk Assessment and TEsting (GENERATE) study.
Authors: Matthew B. Yurgelun, Chinedu I. Ukaegbu, C. Sloane Furniss, Barbara Kenner, Alison Klein, Andrew M. Lowy, Florencia McAllister, Maureen E Mork, Scott H. Nelson, Alison Robertson, Jill E. Stopfer, Meghan Underhill, Allyson J. Ocean, Lisa Madlensky, Gloria M. Petersen, Judy Ellen Garber, Scott Michael Lippman, Michael Goggins, Anirban Maitra, Sapna Syngal
Journal: Journal of Clinical Oncology (2020)

TPS779 Background: 4-10% of PDAC patients harbor pathogenic germline variants in cancer susceptibility genes, including APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, and TP53. For families with such pathogenic variants, the greatest potential impact of germline testing is to identify relatives with the same variant (cascade testing), thereby providing the opportunity for early detection and interception of PDAC and other associated cancers. Numerous factors limit cascade testing in real-world practice, including family dynamics, widespread geographic distribution of relatives, access to genetic services, and misconceptions about the importance of germline testing, such that the preventive benefits of cascade testing are often not fully realized. The primary aim of this study is to analyze two alternative strategies for cascade testing in families with inherited PDAC risk. Methods: 1000 individuals with a confirmed pathogenic germline variant in any of the above genes in a 1 st /2 nd degree relative and a 1 st /2 nd degree relative with PDAC will be remotely enrolled through the study website (www.GENERATEstudy.org) and randomized between two methods of cascade testing (individuals with prior genetic testing will be ineligible): Arm 1 will undergo pre-test genetic education with a pre-recorded video and live interactive session with a genetic counselor via a web-based telemedicine platform (Doxy.me), followed by germline testing through Color Genomics; Arm 2 will undergo germline testing through Color Genomics without dedicated pre-test genetic education. Color Genomics will disclose results to study personnel and directly to participants in both arms. All participants will have the option of pursuing additional telephone-based genetic counseling through Color Genomics. The primary outcome will be uptake of cascade testing. Secondary outcomes will include self-reported genetic knowledge, cancer worry, distress, decisional preparedness, familial communication, and screening uptake, which will be measured via longitudinal surveys. Enrollment is underway nationwide as of May, 2019. Clinical trial information: NCT03762590.
Case 22-1977
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Warren M. Zapol, Eugene J. Mark
Journal: New England Journal of Medicine (1977)

Presentation of CaseA 23-year-old woman was admitted to the hospital because of multiple traumatic injuries.She was well until the evening before admission, when she was involved in a motor-vehicle accident. She was taken to another hospital, where the blood pressure was 70/40 mm Hg. Examination disclosed that she was responsive and able to move all extremities. The left pupil was initially unresponsive to light, later reactive and then again unresponsive. The trachea was intubated, and penicillin, dexamethasone and a transfusion of whole blood were administered. She was transferred to this hospital eight hours after the accident.The temperature . . .
Randomized double-blind phase II study of maintenance pembrolizumab versus placebo after first-line chemotherapy in patients (pts) with metastatic urothelial cancer (mUC): HCRN GU14-182.
Authors: Matt D. Galsky, Sumanta K. Pal, Amir Mortazavi, Matthew I. Milowsky, Saby George, Sumati Gupta, Mark T. Fleming, Long H. Dang, Daniel M. Geynisman, Radhika Walling, Robert S. Alter, Erwin L. Robin, Jue Wang, Shilpa Gupta, David D. Chism, Joel Picus, George Philips, David I. Quinn, Noah M. Hahn, Menggang Yu
Journal: Journal of Clinical Oncology (2019)

4504 Background: Platinum-based chemotherapy for 1st-line treatment of pts with metastatic urothelial cancer (mUC) is typically administered for a fixed duration followed by observation until recurrence. PD-1 blockade with pembro improves survival of pts with mUC progressing despite platinum-based chemotherapy. We explored the potential benefit of earlier use of PD-1 blockade using a "switch maintenance" approach. Methods: Pts with mUC achieving at least stable disease after up to 8 cycles of 1st-line platinum-based chemotherapy were enrolled. Pts were randomized 1:1 to pembro 200 mg IV q3 weeks versus placebo for up to 24 months; pts progressing on placebo could cross over to pembro. Randomization was stratified based on pre-chemotherapy visceral metastases (Y/N) and response to 1 st -line chemotherapy (CR/PR vs. SD). The primary objective was to determine the progression-free survival (PFS) as per irRECIST among pts treated with pembro versus placebo. Results: Between 12/2015 and 11/2018, 107 pts were randomized to placebo (n=52) versus pembro (n=55). The baseline pt characteristics are shown in the Table. Pts randomized to placebo and pembro received a median of 6 and 8 cycles, respectively. Excluding patients with baseline CRs, the objective response rate was 12% (5/42) on placebo and 22% (10/46) on pembro. Grade 3-4 treatment emergent adverse events occurred in 48% of pts on placebo and 56% on pembro. At a median follow-up of 14.7 months, 41 pts have died and 26/52 pts randomized to placebo have crossed over to pembro. PFS was significantly longer in patients randomized to pembro vs. placebo (Maximum Efficiency Robust Test p=0.036; log-rank p = 0.038). The 18-month restricted mean progression-free survival time was 5.6 months with placebo and 8.2 months with pembro (p=0.023). Conclusions: Switch maintenance pembro may “deepen” responses achieved with 1 st -line chemotherapy. Switch maintenance pembro prolongs PFS in pts with mUC completing 1 st -line platinum-based chemotherapy. Clinical trial information: NCT02500121. [Table: see text]