tbuckley/cabot-search huggingface dataset:
Late health outcomes in survivors of Wilms tumor: A report from the St. Jude Lifetime (SJLIFE) cohort study.
Authors: Kayla L. Foster, Daniel M. Green, Sedigheh Mirzaei Salehabadi, Mengqi Xing, Kirsten K. Ness, Kevin R. Krull, Tara M. Brinkman, Matthew J. Ehrhardt, Wassim Chemaitilly, Stephanie B Dixon, Nickhill Bhakta, Rachel Christine Brennan, Matthew J. Krasin, Andrew M. Davidoff, Leslie L. Robison, Melissa M. Hudson, Daniel A. Mulrooney
Journal: Journal of Clinical Oncology (2021)

10038 Background: We aimed to characterize late health, neurocognitive, and physical performance outcomes among survivors of Wilms tumor. Methods: Wilms tumor survivors (n = 280), ≥ 5 years from diagnosis, participating in SJLIFE were clinically assessed along with a community control sample (n = 625). Health outcomes were graded per a modified Common Terminology Criteria for Adverse Events (grade 1 [mild] to grade 4 [life threatening]). Standardized neurocognitive testing was graded using age-adjusted z-scores. Aerobic function (six-minute walk), mobility (timed up and go) and flexibility (sit and reach) were assessed. Associations between treatment exposures and prevalent conditions were examined by multivariable logistic regression, adjusted for current age, sex and race. Results: Survivors (59% female, 73% white), median age 3 years (range 0-15) at diagnosis and 31 years (9-58) at evaluation, were comprehensively evaluated on the St. Jude campus. Two-thirds (67%) were treated with doxorubicin (median dose 175 mg/m 2 range 52-490), 167 (60%) received abdominal radiation (median dose 12 Gy range 8.8-61.2) and 25% received chest radiation (12 Gy range 9-44). By age 40 years, survivors averaged 12.7 (95% confidence interval [CI] 11.7-13.8) grade 1-4 and 7.5 (CI 6.7-8.2) grade 2-4 conditions, compared to 4.2 (CI 3.9-4.6) and 2.3 (CI 2.1-2.5), respectively, among controls. The most prevalent medical conditions (grade ≥ 2) are reported in the table. Abnormal glucose metabolism was associated with abdominal radiation (relative risk [RR] 5.1 CI 1.4-19.0); restrictive pulmonary defects with chest radiation (RR 24.0 CI 3.2-180); and cardiomyopathy (RR 15.6 CI 1.9-128), pulmonary diffusion (RR 4.5 CI 1.3-15.1), and chronic kidney disease (RR 4.5 CI 1.3-16.1) with doxorubicin exposure. Survivors had a three-fold higher risk (standardized incidence ratio 3.5, CI 2.2-6.6) for subsequent neoplasms. Impairments (grade ≥ 2) in executive function (20% vs. 12%), attention (17% vs. 9%), memory (21% vs. 10%), and processing speed (20% vs. 8%) were more frequent in survivors than controls (p &lt; 0.05). Impairments in aerobic function (13.6%), mobility (13.6%), and flexibility (11.1%) were higher than expected (p &lt; 0.01). Significant associations were not identified between treatment exposures and neurocognitive or physical performance outcomes. Conclusions: Systematic clinical assessment identified a significant burden of chronic health conditions and previously unrecognized neurocognitive and physical performance limitations in survivors of Wilms tumor.[Table: see text]
Cholestatic Liver Disease: Current Treatment Strategies and New Therapeutic Agents
Authors: Sho Hasegawa, Masato Yoneda, Yusuke Kurita, Asako Nogami, Yasushi Honda, Kunihiro Hosono, Atsushi Nakajima
Journal: Drugs (2021)

Cholestatic liver disease is a disease that causes liver damage and fibrosis owing to bile stasis. It is represented by primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), but the pathophysiological pathways that cause bile stasis in both diseases are different. The pathogenesis of the disease is still unclear, although autoimmune mechanisms have been postulated and partially elucidated. Although the disease may progress slowly with only mild liver dysfunction, it may progress to liver cirrhosis or liver failure, which require liver transplantation. As a medical treatment, ursodeoxycholic acid is widely used for PBC and has proved to be very effective against disease progression in cases of PBC. On the other hand, its efficacy is limited in cases of PSC, and the research and development of various drugs are underway. Furthermore, the clinical course of both diseases is quite variable, making the design of clinical trials fairly difficult. In this review, we present the general natural history of PBC and PSC, and provide information on the latest drug therapies currently available and those that are under investigation.
Specialty representation on national comprehensive cancer network guideline committees.
Authors: Bismarck Odei, Temitope Agabalogun, Erika Bello-Pardo, Christina C. Huang, Daniel Vanderbilt, Seyi Omeh, Fumiko Chino
Journal: Journal of Clinical Oncology (2021)

11041 Background: Among the National Comprehensive Cancer Network (NCCN) guidelines, the existence of Category 1 evidence for cancer management decisions remains low, resulting in the reliance on multispecialty perspective to determine optimal treatment approach. Multiple studies suggest that the specialty composition of oncological teams is important in the trajectory of decision-making. Consequently, we sought to determine if there was adequate representation of radiation oncologists (ROs) on NCCN committees (NCMs). Methods: NCMs with Category 1 or 2A recommendations for radiotherapy use were identified. Committee members were documented including specialty, academic rank, and committee role. H-index and gender was assessed for each member. A minimum arbitrary threshold of &lt; 10% was used to define underrepresentation of ROs. Univariate and multivariate (MVA) logistic regression identified factors predictive of underrepresentation. Results: Of 57 assessed guidelines, 38 (66.7%) NCMs recommended radiation as Category 1 or 2A from which a total of 1284 committee members were identified. Median committee size was 33 (range 29-38). Overall, 42.2% were Medical Oncologists (MOs), 23.9% were Surgical Oncologists (SOs), and 11.5% were ROs [22.4% were a mix of Radiologists, Pathologists, other specialty physicians, and non-physician members like Patient Advocates]. ROs constituted 4.4% of NCM Chairs (MOs: 68.9%, SOs: 13.3%, Other: 13.3%); 29% of Vice Chairs (MOs: 35.5%, SOs: 35.5%); and 5.9% of the discussion writing committee (MOs: 70.6%, SOs: 23.5%). The representation of ROs was highest for Head/ Neck Cancer NCM (38.8%) and Prostate Cancer NCM (25.8%). 42% of the NCMs recommending radiation had &lt; 10% representation of ROs; 17% of guidelines recommending radiation had 1 or less RO including 4 NCMs which did not have a single RO committee member. On univariate analysis, factors predictive of RO underrepresentation were low SO representation (p = 0.038) and low median H-index of the NCM (p = 0.013); low proportion of full professors trended towards significance (p = 0.060). On MVA, median H-index had a negative association with RO underrepresentation (p = 0.038) —no association was found to rank, gender or specialty. Conclusions: Our study shows alarmingly low representation of ROs among NCCN committees which include radiation as a Category 1 or 2A recommendation. This can both limit the discussion during guideline development and negatively impact the diversity of perspectives in management recommendations. Efforts to ensure more proportional representation of ROs on NCCN guideline committees are warranted including exploring potential barriers to committee leadership.
Differences in transitions of care among cancer patients with and without venous thromboembolism (VTE) events.
Authors: Cinduja Nathan
Journal: Journal of Clinical Oncology (2021)

e18636 Background: Transitions of care are an important part of medical care, as they provide opportunities to address patient concerns, refine goals to match current needs and prevent unforeseen complications and comorbidities. One such common and prevalent comorbidity amongst cancer patients is venous thromboembolism (VTE) events. Common VTE events include the occurrence of pulmonary embolism (PE), deep vein thrombosis (DVT) or both at the time of diagnosis or any time thereafter. It is estimated that approximately 4–20% of cancer patients will experience a VTE. Cancer patients developing VTE is a serious concern as it can adversely affect the patients’ quality of life and reduce overall survival rates and prognosis. Methods: This study is designed as a case control study. The subject group consists of 87 cancer patients who had one or several VTE events after their cancer diagnosis. Patients were selected from the UVM Medical Center electronic health record database. The goal of this project was to quantify and compare the average number of transitions of care in cancer patients with and without venous thromboembolism (VTE) events. This was achieved by reviewing the patients charts three months following a VTE event and evaluating whether these patients had a greater number of transitions compared to the three months prior to their VTE event. Transitions of care in our study were defined as office visits, ED visits, and inpatient admissions related to their VTE. Results: Initial evaluation of the results showed that there were more transitions of care amongst cancer patients with a VTE than without. Preliminary data of the 87 patients shows that patients who developed a VTE event after their cancer diagnosis had on average 1.3 more transitions of care within the three months following their VTE event compared to cancer patients without a VTE event. A t test will be used to determine whether the difference between the means (number of transitions of care) of the two groups (cancer patients with VTE and those without VTE) is significant. Conclusions: The implications of having greater transitions of care amongst cancer patients with VTE events are profound. Having more transitions of care exemplifies better implementation, patient care and involvement of health care teams given a history of VTE. Furthermore, the results of this study will provide further insight on ways to improve clinical outcomes and oncology patient care given a history of VTE.
BREAKWATER: Randomized phase 3 study of encorafenib (enco) + cetuximab (cetux) ± chemotherapy for first-line (1L) treatment (tx) of <i>BRAF</i> V600E-mutant (<i>BRAF</i><sup>V600E</sup>) metastatic colorectal cancer (mCRC).
Authors: Scott Kopetz, Axel Grothey, Rona Yaeger, Fortunato Ciardiello, Jayesh Desai, Tae Won Kim, Tim Maughan, Eric Van Cutsem, Harpreet Singh Wasan, Takayuki Yoshino, Michelle L. Edwards, Adele Golden, Ashwin Gollerkeri, Josep Tabernero
Journal: Journal of Clinical Oncology (2021)

TPS3619 Background: Approximately 10% of patients (pts) with mCRC have BRAF mutations (mostly V600E). 1L tx options for BRAF V600E mCRC are limited to cytotoxic chemotherapy ± anti-VEGF or anti-EGFR, or immune checkpoint inhibitors in pts with MSI-H tumors. In Europe, Japan, and USA, the combination of BRAF inhibitor enco + EGFR inhibitor cetux is approved for tx of BRAF V600E mCRC after prior therapy. In BEACON CRC, enco + cetux resulted in a median overall survival (OS) of 9.3 months (95% confidence interval [CI]: 8.0–11.3) and an objective response rate (ORR) of 19.5% (95% CI: 14.5%–25.4%) in previously treated pts with BRAF V600E mCRC (median follow-up: 12.8 months); 57.4% of pts had grade 3/4 adverse events (AEs); 9% discontinued due to AEs. Given the poor prognosis of pts with BRAF V600E mCRC and based on the efficacy and tolerability of enco + cetux from BEACON CRC, BREAKWATER will evaluate efficacy and safety of enco + cetux ± chemotherapy in tx-naive pts with BRAF V600E mCRC. Methods: BREAKWATER is an open-label, global, multicenter, randomized, phase 3 study with a safety lead-in (SLI). Approximately 60 and 870 pts will be enrolled in the SLI and phase 3 parts of the study, respectively. Pts must have BRAF V600E mCRC (determined using tumor tissue or blood); ECOG performance status 0/1; and adequate bone marrow, hepatic, and renal function. Pts in the SLI must have evaluable disease (RECIST v1.1) and have received ≤ 1 prior tx regimen; those previously treated with a BRAF or EGFR inhibitor, or both oxaliplatin and irinotecan, will be excluded. Pts in the phase 3 study must have measurable disease and be tx naive for metastatic disease. Study tx and endpoints are shown in the table. Enrollment began on 6 January 2021. Clinical trial information: NCT04607421. [Table: see text]
Cancer disparities among patients with advanced metastatic breast cancer.
Authors: Diana Saravia, Leah Elson, Hong Liang, Nadeem Bilani, Elizabeth Blessing Elimimian, Zeina A. Nahleh
Journal: Journal of Clinical Oncology (2021)

e18566 Background: We previously elucidated sociodemographic factors associated with risk-of-death, in a subgroup of patients with Stage IV human epidermal growth factor 2 (HER)+ breast cancer. To further understand determinants of disparities in all subgroups of stage IV breast cancer, this study sought to evaluate factors which are predictive of overall survival (OS) in a cohort of patients with metastatic breast cancer (MBC), according to the following subtypes: 1) estrogen receptor (ER)+ or progesterone receptor (PR)+ and (HER)-, (2) (ER+ or PR+) and HER+, (3) (ER- and PR-) and HER-, or (4) (ER- and PR-) and HER+. Methods: Study population included patients with MBC, extracted from the National Cancer Database, treated between 2010 and 2016. Descriptive statistics were used to summarize patient characteristics, and chi-square tests were performed to compare patient characteristics, by ethnic group (white, black, Hispanic, Asian, and other). Multivariate Cox regression models with backward elimination (using significance level of p&lt;0.05) were utilized to compare overall survival among patient cohorts. In addition, Kaplan-Meier survival curves of patient cohort were also produced. Statistics were performed using SAS. Results: Records from n= 47,032 patients were included, the majority were 50 years or older, white, and treated with hormonal therapy. With a median follow-up time of 2.3 years, disparities in OS were observed; black patients were more likely to suffer death (HR=1.12 (1.08-1.16), p&lt;0.0001), compared to white patients. Additional factors contributing to risk of death in MBC included: being male (HR=1.12, (1.02-1.23), p=0.019), having visceral involvement compared to bone only (HR=1.52, (1.05-1.28), p&lt;0.0001), income &lt; $38,000 (HR=1.13 (1.09-1.17), p&lt;0.0001), being on government insurance (HR=1.24, (1.20-1.27), p&lt;0.0001, and having Triple Negative Breast Cancer (ER- and PR-) and HER- status (HR=1.68 (1.60-1.75) p&lt;0.0001). Patients who receive chemotherapy, not hormonal therapy (HR=1.25 (1.2 – 1.3), p&lt;0.0001), were found to have worse prognosis possibly reflecting biology of disease at presentation and lack of specific targeted therapy. Conclusions: This study confirms that sociodemographic disparities exist in OS among patients within the same stage of MBC, and regardless of receptor status subtypes. Clinical practice should focus on closing disparities gaps for those with advanced and MBC, especially among Black, impoverished, and male patients. Better treatment approaches should be sought for patients with visceral metastasis and those diagnosed with triple negative receptor status, who continue to suffer from worse outcomes.
Patterns of presentation among New Zealand Māori with pancreatic cancer at Lakes District Health Board.
Authors: Laura Camburn, Prashanth Hari Dass
Journal: Journal of Clinical Oncology (2021)

e18553 Background: New Zealand (NZ) Māori have higher rates of pancreatic cancer than other ethnic groups in NZ. Lakes District Health board (LDHB) has one of the highest proportion of Māori patients within New Zealand, 34.7% compared to 15.7% nationally. We aimed to review the patterns of presentation of patients diagnosed with pancreatic cancer at LDHB between ethnicities. Methods: Patients diagnosed with pancreatic cancer at LDHB between 01 Jul 2014 to 31 Mar 2020 were identified using the faster cancer treatment data and regional hospice referral data. This was cross checked against surgical and oncology referrals. Electronic notes were reviewed to collect data on ethnicity, patient demographics, &amp; presentation. Results: 69 patients were identified; 25 Māori patients and 44 New Zealand European (NZE) patients. The mean age at diagnosis was 63.4 years for Māori and 73.4 years for NZE patients. 22 (88%) Māori patients were below the age of 75 at diagnosis compared to 24 (55%) NZE patients. In both groups there were more affected males than females. Risk factors such as positive smoking history, obesity and diabetes were more prevalent in Māori patients (80% v 43%, 40% v 16%, 44% v 20% respectively). Māori were more likely to present with metastatic disease compared to non-Māori at presentation (64% v 52%). Conclusions: Māori pancreatic cancer patients in our region were more likely to present younger with metabolic syndrome and more advanced disease compared to NZE patients.
Thirty-day readmission after percutaneous coronary intervention with drug eluting stent in patients with active malignancy.
Authors: Hugo Macchi, Miguel Salazar, Juan Del Cid Fratti, Shristi Upadhyay, Binav Baral, Trilok Shrivastava, Estefania Gauto, Juan Adolfo Cattoni
Journal: Journal of Clinical Oncology (2021)

e18601 Background: Reducing the 30-day readmission is one of the quality performance measures upon which hospitals are being evaluated. Readmissions represent a significant economic burden to the patients and the health care system. Index admission for myocardial infarctions requiring PCI with a concurrent diagnosis of malignancy represents a critical part of the population due to the association between cancer and the pro-thrombotic state that renders them at high risk of readmission. By harnessing the power of large datasets such as the NRD (National Readmission Database), we sought to find associations that, together, could aid in the development of better public and private policies that would make patient care more efficient. Methods: We conducted a retrospective study of the 2017 National Readmission Database (NRD) of adult patients readmitted within 30 days after an index admission for myocardial infarction requiring PCI with a concurrent diagnosis of malignancy. We aimed to identify the 30-day readmission rate, mortality, healthcare-related utilization resources, and independent readmission predictors. Results: A total of 8,350 patients with malignancy underwent PCI. The 30-day readmission rate was 17.8%. The main causes for readmission were sepsis, ventricular fibrillation, recurrent STEMI. Compared to initial admissions, readmitted patients were less likely to require mechanical ventilation (7.3% vs. 5.2%; P = 0.05), intra-aortic balloon pump placement (4.1 vs 0.4; P &lt; 0.01), IMPELLA device use (4.0 vs 0.3; P &lt; 0.01), less had private insurance (16.2% vs 12.9%; P = 0.02), less developed shock (7.7% vs 3.2%; P &lt; 0.01), &amp; less had major bleeding (2.0% vs 0.1%; P &lt; 0.01). Readmission was associated with lower in-hospital mortality rate (1.5% vs. 0.1%; P &lt; 0.01), but more likely to require hemodialysis (4.3% vs 6.6%; P &lt; 0.01), &amp; have venous thromboembolism (VTE) (1.9% vs 3.2%; P &lt; 0.01). The total health care in-hospital economic burden of readmission was $937 million in total charges for patients and $224 million in total costs for hospitals. Independent predictors of readmission were female gender, the disposition to a short-term hospital or skilled nursing facility, prolonged length of stay, inpatient hemodialysis, and VTE episodes. Conclusions: Readmissions after PCI in patients with malignancy are associated with a lower in-hospital mortality rate but pose a high health care burden. We identified potential risk factors that, if targeted, could lead to a reduction in readmissions after PCI in cancer patients, &amp; therefore decrease health care costs.
Heart Failure Hospitalization in Adults Receiving Hemodialysis and the Effect of Intravenous Iron Therapy
Authors: Pardeep S. Jhund, Mark C. Petrie, Michele Robertson, Patrick B. Mark, Michael R. MacDonald, Eugene Connolly, Stefan D. Anker, Sunil Bhandari, Kenneth Farrington, Philip A. Kalra, David C. Wheeler, Charles R.V. Tomson, Ian Ford, John J.V. McMurray, Iain C. Macdougall
Journal: JACC Heart Failure (2021)
Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma
Authors: Nicolas Jacquelot, Cyril Seillet, Minyu Wang, Angela Pizzolla, Yang Liao, Soroor Hediyeh-zadeh, Sharon Grisaru-Tal, Cynthia Louis, Qiutong Huang, Jaring Schreuder, Fernando Souza-Fonseca-Guimaraes, Carolyn A. de Graaf, Kevin Thia, Sean Macdonald, Mary Camilleri, Kylie Luong, Shengbo Zhang, Michael Chopin, Tristan Molden-Hauer, Stephen L. Nutt, Viktor Umansky, Bogoljub Ciric, Joanna R. Groom, Paul S. Foster, Philip M. Hansbro, Andrew N. J. McKenzie, Daniel H. D. Gray, Andreas Behren, Jonathan Cebon, Eric Vivier, Ian P. Wicks, Joseph A. Trapani, Ariel Munitz, Melissa J. Davis, Wei Shi, Paul J. Neeson, Gabrielle T. Belz
Journal: Nature Immunology (2021)
Outcome of breast cancer patients treated with chemotherapy during pregnancy compared with non-pregnant controls.
Authors: Frederic Amant, Valentina Nekljudova, Charlotte Maggen, Fenja Seither, Patrick Neven, Elyce Cardonick, Sabine Schmatloch, Kristel Van Calsteren, Tatjana Cordes, Jorine de Haan, Christianne AR Lok, Christina Bechtner, Ingrid A. Boere, Mina Mhallem Gziri, Christine Solbach, Hanne Lefrère, Andreas Schneeweiss, Isabell Witzel, Sabine Seiler, Sibylle Loibl
Journal: Journal of Clinical Oncology (2021)

515 Background: Overall a diagnosis of breast cancer during pregnancy (BCP) appears not to impact maternal prognosis if standard treatment is offered. However, caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients. This cohort study was designed to focus on the maternal prognosis of BCP patients that receive chemotherapy during pregnancy. Methods: The outcome of BCP patients treated with chemotherapy during pregnancy was compared to non-pregnant breast cancer patients treated with chemotherapy, diagnosed after 2000, excluding postpartum diagnosis and with an age limit of 45 years. The data was registered by two multicentric registries (the International Network of Cancer, Infertility and Pregnancy and the German Breast Cancer Group) that collect both retro-and prospectively breast cancer data. Cox proportional hazards regression was used to compare disease-free (DFS) and overall survival (OS) between both groups, adjusting for age, stage, grade, hormone receptor status, human epidermal growth factor 2 status and histology, weighted by propensity scoring in order to account for the differences in baseline characteristics between pregnant patients and controls. Results: In total, 662 pregnant and 2081 non-pregnant patients, were eligible for analysis. Median age at diagnosis was 34 (range 22-47) years for pregnant and 38 (range 19-45) years for non-pregnant patients. Pregnant patients were more likely to have stage II breast cancer (60.1% vs 56.1%, p = 0.035), grade 3 tumors (74.0% vs 62.2%, p &lt; 0.001), hormone receptor-negative tumors (48.4% vs 34.0%, p &lt; 0.001) or triple-negative breast cancer (38.9% vs 26.9%, p &lt; 0.001). Median follow-up was 66 months. DFS and OS were comparable for pregnant and non-pregnant patients (DFS: HR 1.02, 95%CI 0.82-1.27, p = 0.83; OS: HR 1.08, 95% CI 0.81-1.45, p = 0.59). A subgroup analysis of 339 women that received more than 60% of chemotherapy during pregnancy (cut-off at median) revealed a comparable survival compared to non-pregnant women (DFS: HR 0.81, 95%CI 0.62-1.06, p = 0.13; OS: HR 0.85 95% CI 0.58-1.23, p = 0.39). Conclusions: Pregnancy-induced alternations in chemotherapy concentration do not seem to affect maternal prognosis in breast cancer patients. These results support initiation of chemotherapy for BCP where indicated for oncological reasons.