tbuckley/cabot-search huggingface dataset:
Case 45-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Andrew I. Schafer, Alain Marion
Journal: New England Journal of Medicine (1985)

Presentation of Case First admission. A 56-year-old man was admitted to the hospital because of chronic liver disease and diabetes mellitus.There was a history of chronic liver disease of at least 10 years' duration. For about five years the patient was known to have diabetes mellitus, which was controlled by diet alone. Several years before admission an upper gastrointestinal series was reported to show splenomegaly but no esophageal varices. During the five years before admission repeated examinations of the blood revealed chronic leukopenia, severe thrombocytopenia, hypoprothrombinemia, and mild anemia; a liver biopsy was believed to be contraindicated. There was . . .
Breast MRI as a radiomic biomarker of immune enrichment in HER2+ breast cancer.
Authors: Laura Kennedy, Grace Durenberger, Sasha E. Stanton, Shaveta Vinayak, Suzanne Dintzis, Savannah C. Partridge, Vijayakrishna K. Gadi
Journal: Journal of Clinical Oncology (2019)

e14281 Background: Trastuzumab is an important drug in the treatment (tx) of HER2+ breast cancer, but not all tumors are responsive. Immune-enriched tumors have a better response to tx, and a biomarker to identify these tumors would be valuable. Multiparametric functional MRI is a non-invasive technique that can assess the entire tumor without the sampling error of biopsy. In this pilot study, we evaluate breast MRI as a potential biomarker for tumor immune response to trastuzumab. Methods: Women with de novo cT1-2N0 HER2+ breast cancer were enrolled and received paired multiparametric breast MRI examinations (including DWI and DCE sequences) prior to and ~2 weeks after a single dose of trastuzumab, followed by surgery or biopsy (if additional neoadjuvant tx planned). Tumor peak signal enhancement ratio (SER) and mean apparent diffusion coefficient (ADC), reflecting tissue perfusion and tissue cellularity, were determined from the images. Pre- and post-tx tissue were immunologically profiled with TIL counts and an immune-focused RNA gene expression panel. SER and ADC were correlated with TIL and RNA gene expression using Spearman’s rho. Results: To date, 8 women have enrolled and 6 had pre- and post-tx tissue available. The primary endpoint was correlation between SER and ADC measurements with tumor TILs. Secondary endpoints included correlating SER with angiogenesis and inflammation markers and correlating changes in SER and ADC with apoptosis/cell death markers. About half of the patients had TIL-enriched (TIL≥ 50%) tumors at baseline, and after trastuzumab the majority of tumors remained enriched or had an increase in TILs. Results suggest that pre-tx ADC had a negative correlation with TILs by histology and gene expression, although correlations did not reach statistical significance in this small cohort. Results also suggest a strong correlation between pre-tx SER and VEGF-A (r = 0.83) with a trend towards significance (P = 0.10). A decrease in SER post-tx had a strong correlation with an increase in caspase 3 expression (r = -0.85, p = 0.05), which suggested tx effect. Conclusions: Functional MRI may provide a novel biomarker of breast tumor immune response to trastuzumab. Results from additional patients will be available at the meeting.
Abstract 11894: Deficiencies of Water-soluble Vitamin Intake Predict Shorter Event-free Survival in Patients With Heart Failure
Authors: Kyoung Suk Lee, Jae-Hyeong Park, Debra K Moser, Sandra B Dunbar, Susan J Pressler, Terry A Lennie
Journal: Circulation (2016)

Introduction: Water-soluble vitamins play an important role in producing adenosine triphosphate and decreasing oxidative stress. Because water-soluble vitamins are not stored, inadequate dietary intake leads to water-soluble vitamin deficiencies, which may be associated with adverse health effects. Patients with heart failure (HF) are at risk for water-soluble vitamin deficiencies even if their water-soluble vitamin intakes meet dietary recommended intake as diuretics are routinely prescribed to this population. However, there are few studies, which have measured the relationship between deficiencies of water-soluble vitamin intake and outcomes in HF. Purpose: To determine whether deficiencies of water-soluble vitamin intake predicted event-free survival in patients with HF Methods: Using a prospective, observational study design, patients with HF were recruited from HF clinics. A total of 216 patients with HF (61years; 34.3% female; 53.7% NYHA I/II; 71.8% LVEF ≤ 40%) were included in this analysis. Four-day food diary analyzed by Nutrition Data System-Research software was used to determine water-soluble vitamin dietary deficiencies (i.e., 8 B vitamins and vitamin C). Event-free survival was defined as a composite endpoint of all-cause death, cardiac hospitalization, or emergency department visit for cardiac reasons. Monthly calls to patient or family and medical record reviews were used to determine event-free survival for 12 months. Results: The average number of water-soluble vitamin deficiencies was 1 (SD 1.24) with the range of 0 -7. There were 63 events during the median follow-up of 356 days. Multivariable Cox regression showed that each unit increase in the number of water-soluble vitamin deficiencies was associated with a 1.3-fold increase in risk for an event (95% CI 1.02-1.66), after adjusting for age, gender, NYHA functional class, reduced LV function (i.e., LVEF≤ 40%), N-terminal pro B-type natriuretic peptide, total comorbidities, and use of diuretics (yes/no). Conclusions: Deficiencies of water-soluble vitamin intake were associated with a shorter event-free survival in patients with HF. This result suggests a potential benefit to correcting water-soluble vitamin deficiencies in this population.
Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial
Authors: Elisa A Rozeman, Alexander M Menzies, Alexander C J van Akkooi, Chandra Adhikari, Carolien Bierman, Bart A van de Wiel, Richard A Scolyer, Oscar Krijgsman, Karolina Sikorska, Hanna Eriksson, Annegien Broeks, Johannes V van Thienen, Alexander D Guminski, Alex Torres Acosta, Sylvia ter Meulen, Anne Miek Koenen, Linda J W Bosch, Kerwin Shannon, Loes M Pronk, Maria Gonzalez, Sydney Ch'ng, Lindsay G Grijpink-Ongering, Jonathan Stretch, Stijn Heijmink, Harm van Tinteren, John B A G Haanen, Omgo E Nieweg, Willem M C Klop, Charlotte L Zuur, Robyn P M Saw, Winan J van Houdt, Daniel S Peeper, Andrew J Spillane, Johan Hansson, Ton N Schumacher, Georgina V Long, Christian U Blank
Journal: The Lancet Oncology (2019)
Gender differences in prognostic value of immune-related biomarkers in colon cancer patients randomized to surgery or surgery and adjuvant chemotherapy treatment.
Authors: Lisa Villabona, Giuseppe V. Masucci, Peter Ragnhammar
Journal: Journal of Clinical Oncology (2019)

3603 Background: HLA-A*02, a common allele in the Scandinavian population, is a negative prognostic factor in epithelial ovarian cancer. It is a strong predictor of patient outcome, only inferior to clinical staging. This prognostic trait in epithelial ovarian cancer is stronger by the presence of the gene compared with the expression of its protein, MHC class I. Microsatellite instability (MSI) is used as a biomarker for prognosis and is suggested an increased tumor mutational burden which can make the tumor more susceptible for T cell mediated immunotherapy. Our aim was to analyze the prognostic markers HLA-A*02 genotype, MHC class I on tumor cells, the CD8+ lymphocyte infiltration and MSI status in colon cancer patients with randomized treatment. Methods: Clinical information and primary tumors were collected from 520 colon cancer patients and followed for overall survival for 120 months. Patients hade stage II and III colon cancer and were randomized to surgery alone or surgery and adjuvant chemotherapy. HLA-A*02 genotype was determined by conventional PCR. MHC class I, MSI status and CD8+ lymphocyte infiltration were determined by immunohistochemistry. Results: Female patients with a stage III tumor and HLA-A*02 genotype had a better outcome if they had received adjuvant chemotherapy instead of just surgery (p = 0.03), whereas this was not the case for patients with other HLA-A genotypes or in the male patients where HLA-type did not correlate to outcome. MHC class I expression did not act as a prognostic factor, however the presence of CD8+ lymphocytes in the invasive margin and inside the tumor was a positive prognostic factor for overall survival (p = 0.01), although only statistically significant in the male patients (p = 0.03). 21% patients had a tumor with MSI (23% of the female and 19% of the male patients respectively). MSI tumors had a slightly better outcome and this was irrespective of gender and HLA-type. Conclusions: The prognostic traits of HLA-A*02 appear in this colon cancer cohort to act differently in male and female patients. Also CD8+ infiltration is different between genders. These findings suggest that men and women may have two different immune responses to malignancy.
Clinical significance of circulating tumor cells identified by cell-surface vimentin in pancreatic cancer.
Authors: Tao Wei, Qi Zhang, Tingbo Liang, Xueli Bai
Journal: Journal of Clinical Oncology (2019)

e14562 Background: Identification of circulating tumor cells (CTCs) largely rely on epithelial tumor cell marker. Here we sought to interrogate whether cell-surface vimentin could be a biomarker for isolating CTCs potentially with mesenchymal phenotype in pancreatic ductal adenocarcinoma (PDAC). Methods: In total, 100 PDAC patients, 16 patients with intraductal papillary mucinous neoplasm (IPMN), and 30 healthy individuals were enrolled between December 2016 and November 2017. Potential CTCs were captured in 4 ml blood samples by vimentin antibody-coated microfluidic chip. CTCs were defined as vimentin + CD45 - Hoechst + . Results: In vitro experiment showed that vimentin was highly expressed on the surface of pancreatic tumor cells with mesenchymal phenotype. Overall, vimentin + CTCs were detected in 76% of patients with PDAC, but only in 2 out 30 healthy donors. Besides, five patients (31.3%) with IPMN had vimentin + CTCs, and 10 CTCs were identified in one case. Using a cut-off value of two cells/4 ml of blood, 65% PDAC patients were positive for vimentin + CTCs , while the positivity rates for the patients with IPMN and the healthy controls were 25% and 0%, respectively. Combined vimentin + CTCs and CA19-9 offered a favorable diagnostic potency with area under curve of 0.968. Vimentin + CTCs counts correlated with change of tumor burden for patients undergoing resection ( P &lt; 0.01). Significant reduction of CTCs counts was observed after chemotherapy for subjects responding to treatment ( P &lt; 0.05). The paired analysis showed that CTC counts was higher in portal vein blood than peripheral blood for 10 patients with available samples ( P &lt; 0.05). Patients with 2 or more CTCs detected had more advanced disease and poorer differentiated tumor. In addition, preoperative higher CTCs counts correlated with shortened recurrence-free survival (Log-rank test: P = 0.02). Conclusions: Vimentin + CTCs serves as a reliable biomarker in pancreatic cancer. The enrichment of potential mesenchymal CTCs could complement the strategy capturing epithelial CTCs, and provides a way to more thoroughly interrogate the biology and clinical significance of CTCs in PDAC.
Incidence and characteristics of emergency department presentations during immune checkpoint inhibitor therapy.
Authors: Daniel Arnold Smith, Kai Laukamp, Melanie Campbell, Robert Devita, Ariel Ann Nelson, Christopher J. Hoimes, Nikhil H. Ramaiya
Journal: Journal of Clinical Oncology (2019)

e14164 Background: Immune checkpoint inhibitors (ICIs) have emerged as a novel class of anticancer agents with unique response and toxicity profiles. Oncology patients undergoing ICI therapy can present acutely with cancer- or treatment-related complications, but knowledge of these acute clinical presentations is limited. The objective of this study was to investigate the features of emergency department (ED) presentations of patients undergoing ICI therapy. Methods: A retrospective chart review was performed of 1044 adult oncology patients at a single institution from 2010-2018 who underwent treatment with one or more ICI. The number of patient visits to the ED during and up to one month following ICI treatment was recorded, in addition to various clinical and demographic data. These data were compared based on stratification by number of ED visits (0 visits, 1 visit, or ≥2 visits) using Likelihood Ratio Chi-Square and Mann–Whitney U tests. Results: Mean age for the 1044 patients receiving ICI therapy was 64±13 years, with 57% males and 43% females. Primary cancer distribution included 42.0% lung, 24.2% melanoma, 6.9% head &amp; neck, 5.1% kidney, 4.0% bladder, and 17.8% other malignancy. 83.4% of patients were treated with a single ICI, 14.9% with 2 ICIs, and 1.2% with 3-4 ICIs. 56.0% of patients had no ED visits during their treatment duration, 27.0% had 1 ED visit, and 17.0% had ≥2 ED visits. Patients with lung, kidney, and bladder cancer were more likely to present to the ED (p = &lt; 0.001). Black ethnicity was the only demographic feature associated with more ED visits (p = 0.017). Patients receiving ≥2 ICIs or monotherapy with nivolumab, pembrolizumab, or atezolizumab more frequently presented to the ED compared to other ICIs (p = &lt; 0.001). Patients with 1 or ≥2 ED visits had longer durations of ICI therapy (136±12 days and 216±15 days, respectively) compared to patients with no ED visits (127±8 days) (p = &lt; 0.001). Patients with no ED visits also demonstrated better overall survival (p = &lt; 0.001). Conclusions: More frequent ED visits during ICI therapy is statistically associated with several key clinical factors, including primary cancer type, ethnicity, specific ICI agent, ICI therapy duration, and overall survival.
Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma.
Authors: Joshua Dean Horton, Hannah Knochelmann, Kent Armeson, John M. Kaczmar, Chrystal Paulos, David Neskey
Journal: Journal of Clinical Oncology (2019)

2574 Background: Oral cavity squamous cell carcinoma (OCSCC) is a highly prevalent surgically-treated subset of head and neck cancer with frequent recurrence and poor survival. Immunotherapy has demonstrated efficacy in recurrent/metastatic head and neck cancer, but has not been validated in the neoadjuvant presurgical setting. Methods: A Simon two stage design was used in this single-arm, Phase II clinical trial with a preplanned analysis after completion of stage one. The first stage included 9 patients with stage II-IVA OCSCC who received 3-4 biweekly doses of 3mg/kg Nivolumab (anti-programmed death 1 [PD-1]) followed by definitive surgical resection for cure. The primary endpoint was overall response rate to treatment. Secondary endpoints were safety and feasibility. Results: Presurgical Nivolumab therapy resulted in an overall response rate of 44% (95% CI: 14-79%) with four patients having &gt;30% reduction in tumor size consistent with partial response. An additional patient had stable disease while the remaining four patients progressed through treatment. Neoadjuvant Nivolumab was not associated with delays in definitive surgical treatment. There were no grade 3-4 adverse events and no treatment interruptions. At median follow up of 10 months (2-16), there were 4 recurrences in 3 patients and one death. Objective response by RECIST 1.1 criteria on interval imaging predicated eventual pathologic response in 100% of patients. Conclusions: Neoadjuvant presurgical PD-1 blockade is associated with encouraging response rate and demonstrates feasibility and safety for OCSCC. Clinical trial information: NCT03021993.
Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial
Authors: Jason Fangusaro, Arzu Onar-Thomas, Tina Young Poussaint, Shengjie Wu, Azra H Ligon, Neal Lindeman, Anuradha Banerjee, Roger J Packer, Lindsay B Kilburn, Stewart Goldman, Ian F Pollack, Ibrahim Qaddoumi, Regina I Jakacki, Paul G Fisher, Girish Dhall, Patricia Baxter, Susan G Kreissman, Clinton F Stewart, David T W Jones, Stefan M Pfister, Gilbert Vezina, Jessica S Stern, Ashok Panigrahy, Zoltan Patay, Benita Tamrazi, Jeremy Y Jones, Sofia S Haque, David S Enterline, Soonmee Cha, Michael J Fisher, Laurence Austin Doyle, Malcolm Smith, Ira J Dunkel, Maryam Fouladi
Journal: The Lancet Oncology (2019)
Creation of a virtual cancer care network for remote oncology treatment.
Authors: Vida Almario Passero, Andrew Dede Liman, Kaneen Allen, Lucy Speerhas, Jocelyn Lai Tan, Laurie Harrold, Joyce Tokarsky, Kristen Veraldi, Myra Couch, John Hotchkiss, Deborah L Gray, Hema Rai, Jeanne Green, Jenna Shields
Journal: Journal of Clinical Oncology (2019)

6546 Background: The VA Pittsburgh Healthcare System (VAPHS) Virtual Cancer Care Network was launched in January 2018 after we had established an electronic consult service where 555 hematology electronic consults were completed at VAPHS in FY17. The clinical video telehealth (CVT) clinic allows veterans from central Pennsylvania to receive their anticancer therapy at the VA in Altoona, Pennsylvania where the oncology pharmacy, nursing, telehealth, and supportive oncology staff are on site. Patients follow regularly and remotely during treatment via CVT visits with their oncologist located 93 miles away at the VA in Pittsburgh. Methods: A chemotherapy pharmacy and nursing infusion clinic were created at the VA in Altoona. CVT visits started in January 2018. Data including treatment, adverse events defined through CTCAE v5.0, gender, age, zip code, and other details were examined retrospectively. Results: 279 CVT visits for 89 patients were completed January 2018 through Sept 2018. 87 were male, 2 were female. Average age was 70 (range 45-90). Most common primary disease sites were prostate (19.1%), colorectal (13.4%), and lung (9%). 61.8% of patients were on treatment. Non-treatment visits were for surveillance and survivorship. Treatment administered included platinum doublets, fluorouracil doublets, immunotherapy, and oral anticancer therapy. 5.4% of patients had Grade 3-4 events due to febrile neutropenia, increased liver enzymes, and hemolytic anemia. 41.7% had grade 1-2 events due to peripheral neuropathy, neutropenia, anemia, thrombocytopenia, and infusion-related reactions. Using an average commuting speed of 60 mph and a travel cost of $ 0.56 per mile, the total commute distance averted was 49,579 miles. Mean distance averted per patient was 557 miles. Total commute time saved for veterans was 826 hours. Total mileage costs saved for veterans was $27,764. Conclusions: The Virtual Cancer Care Network reduced the travel time and costs for veterans who previously would have travelled from central Pennsylvania to VAPHS for their oncology treatment. Adverse events were tolerable and managed by the VA in Altoona. Integration of CVT secures safe access to cancer care and maintains patients’ primary relationships with their oncologists.
Utility of effect size to define populations with durable clinical outcomes across trials of metastatic colorectal cancer.
Authors: Jeremy D. Kratz, Nataliya Volodymyrivna Uboha, Noelle K. LoConte, Sam Joseph Lubner, Daniel Mulkerin, Kristina Matkowskyj, Anita Ahmed Turk, Carley M. Sprackling, Jens C. Eickhoff, Dustin A. Deming
Journal: Journal of Clinical Oncology (2019)

e15104 Background: ASCO defined clinically meaningful trial endpoints in colorectal cancer (CRC) as absolute overall survival (OS) of 3-5 months and OS hazard ratio (HR) ≤0.67. Few tools predict clinically distinct subgroups from heterogeneous populations. Effect size (Glass’s delta) calculates the absolute difference in clinical outcomes relative to the standard deviation of control group. We hypothesized that effect sizes ≥1 would be useful in predicting subgroup populations of clinical significance for trials with an indeterminate HR. Methods: Prospective phase II-III trials in metastatic CRC were queried from clinicaltrials.gov and cataloged by clinical outcomes of PFS and OS. Effect size was back-calculated from trials reporting 95% confidence intervals and compared with absolute difference in clinical outcome and hazard ratio. Results: 46 prospective trials were evaluable including 49% with biomarker selection, 57% in the first-line setting, and more commonly studied with targeted therapy over chemotherapy (70 v. 30%; p &lt; 0.001). EGFR inhibitors were studied in 34% and VEGF inhibitors in 23%. Both effect size and HR correlated similarly with PFS (correlation coefficients, R = 0.65 vs. 0.76) and OS (R = 0.83 vs. 0.84) across these studies. Of studies with an indeterminate HR (0.69-0.86; n = 24), 10 studies had a significant effect size (Glass’s delta &gt; 1), indicating the potential for sub-populations with improved clinical benefit within the experimental treatment group. These included 4 trials with planned biomarker analyses. Remaining trials were enriched for studies investigating anti-angiogenic therapies (83% vs. 23%, p = 0.001), including bevacizumab, aflibercept, regorafenib, and ramucirumab. Conclusions: Effect size holds potential as a measure to indicate the presence of subpopulations of patients benefiting in clinical trials. Those trials with a significant effect size despite an indeterminate HR should be examined closely for such populations. In CRC, effect size indicates the potential of a subgroup of patients who benefit significantly from anti-angiogenic agents. Further investigations are needed to validate effect size as a tool to delineate improved clinical outcomes from heterogeneous populations.