tbuckley/cabot-search huggingface dataset:
A cost-effectiveness analysis of pretreatment <i>DPYD</i> and <i>UGT1A1</i> screening in patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI+bevacizumab (FOLFIRI+Bev).
Authors: Zachary Rivers, David D. Stenehjem, Pamala Jacobson, Emil Lou, Andrew Nelson, Karen M Kuntz
Journal: Journal of Clinical Oncology (2020)

168 Background: Variants in DPYD and UGT1A1 impact toxicities experienced by patients being treated with FOLFIRI+bev. Testing allows providers to preemptively adjust dosing, reducing the toxicity that patients experience. We assessed the cost-effectiveness of pre-treatment testing for variants in DPYD and UGT1A1 in patients with mCRC receiving FOLFIRI+bev. Methods: We developed a six-state Markov model to compare pre-treatment genetic testing to no testing. The genetic testing arm screened for UGT1A1 and DPYD using a multi-gene panel. Patients were dosed per proposed guidelines (Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group) and allowed dose reductions based on toxicity. In the no-test arm, patients received full doses of FOLFIRI+bev, and dose reductions based on toxicity. Costs included medications, clinic visits, and hospitalizations to treat the disease and adverse events, and were obtained from the literature, adjusted to 2019 $US. Quality-adjusted life years (QALYs) were used to assess effectiveness. We used a US health care system perspective with a 16 week horizon, the average length of time patients were exposed to FOLFIRI+bev in clinical trials. We conducted sensitivity analyses to determine the impact of uncertainty on outcomes. Results: Genetic testing cost $25,563, generating 0.21 QALYs. Standard of care cost $25,515, generating 0.20 QALYs. This resulted in an incremental cost-effectiveness ratio (ICER) of $4963 per QALY gained. Results were sensitive to costs of post-progression care, the probability of carrying UGT1A1 variants, and the impact of low-functioning DPYD variants on side effects. Conclusions: Pre-treatment testing for DPYD and UGT1A1 in patients receiving FOLFIRI+bev for mCRC is cost-effective, well below typical oncology ICERs of $50,000-100,000 per QALY. Further work is needed to characterize the impact of post-progression treatment and supportive care medications.
Topical calcineurin inhibitors for pediatric periorificial dermatitis
Authors: Ayelet Ollech, Rame Yousif, Lacey Kruse, Annette Wagner, Brandi Kenner-Bell, Sarah Chamlin, Duri Yun, Lisa Shen, Karina Vivar, Megan Reynolds, Amy S. Paller, Anthony J. Mancini
Journal: Journal of the American Academy of Dermatology (2020)
Diagnosis and Management of Primary Hyperparathyroidism
Authors: Catherine Y. Zhu, Cord Sturgeon, Michael W. Yeh
Journal: JAMA (2020)

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Circulating tumor DNA (ctDNA) heterogeneity as first- and third-line treatment in patients (pts) with metastatic colorectal cancer (mCRC) treated with panitumumab.
Authors: Christine Megerdichian Parseghian, Karl Beutner, Michael Boedigheimer, Paul Ruff, Timothy Jay Price, Tae Won Kim, Marwan Fakih, Agnes Ang
Journal: Journal of Clinical Oncology (2020)

238 Background: RAS mutations are negative predictors of response to anti-EGFR therapies such as panitumumab in mCRC. Mutations at baseline (BL) and follow-up (FU) during randomized phase 3 studies of first line treatment (1L; study 20050203 [‘203]; panitumumab + fluorouracil, leucovorin and oxaliplatin [FOLFOX4] vs FOLFOX4) were compared with those in third line treatment (3L; study 20100007 [‘0007]; panitumumab + best supportive care [BSC] vs BSC) to assess tumor heterogeneity via ctDNA analysis. Methods: Biomarker analysis was conducted for pts with plasma samples at BL and FU. Samples were analyzed using the Plasma Select-R 63-gene panel (Personal Genome Diagnostics, Inc.), with a limit of detection of 0.1%. Mutations were defined at the amino acid level. The Cox hazard ratio (HR) by sum of RAS mutant allele frequency (MAF) was determined, as were event-free survival (EFS) and best response by RAS mutation status. Results: For all pts with available samples (‘203, n = 120; ‘0007, n = 90), fewer mutations and fewer mutations/gene were observed in the 1L vs 3L setting at BL ( KRAS 2 vs 3 maximum mutations/gene; EGFR 1 vs 4 maximum mutations/gene). In 3L the Cox HR increased continuously with RAS MAF; while this was not found in 1L. In the 1L setting, emergent RAS mutations were not predictive of EFS for FOLFOX4, but were predictive of shorter EFS for panitumumab + FOLFOX4. More panitumumab-treated pts in the 3L setting had detectable RAS mutations emerging from BL to FU (28.6%, 57.1%) vs pts treated in 1L (24.5%, 26.5%). For pts who achieved a partial response, more treated in 1L maintained a higher frequency of wild-type RAS from BL to FU (84.4%, 78.1%) vs pts treated in 3L (95.7%, 43.5%). Conclusions: The overall mutational landscape differs between the 1L vs 3L setting in anti-EGFR–treated mCRC pts. Panitumumab monotherapy in the 3L setting appears to induce greater RAS-specific selective pressure than panitumumab FOLFOX4 combination therapy in 1L, resulting in increased RAS mutations at FU in the 3L setting. The combination of panitumumab + FOLFOX in 1L is associated with delayed emergence of expansion of RAS mutations compared to later line single agent panitumumab.
Ethnicity impact on skin cancer knowledge and quality of life in patients with skin cancer: A survey-based study of white Hispanics and white non-Hispanics
Authors: Ali Rajabi-Estarabadi, Natalie M. Williams, Darren C. Tsang, Isabella Camacho, Sofia Iglesia, Caiwei Zheng, Christina D. Kursewicz, Ariel Eber, Jennifer Tang, Robert S. Kirsner, Keyvan Nouri
Journal: Journal of the American Academy of Dermatology (2020)
Phase I results of the phase I/II study of pembrolizumab in combination with binimetinib in patients with unresectable locally advanced or metastatic triple-negative breast cancer.
Authors: Saranya Chumsri, Mei-Yin Polley, Pulkit Mathur, Aline Reis, Kathleen S. Tenner, Morgan Weidner, Pooja Advani, Alvaro Moreno-Aspitia, Edith A. Perez, Keith L. Knutson
Journal: Journal of Clinical Oncology (2020)

78 Background: Previous study demonstrated that activation of RAS/MAPK pathway is associated with reduced tumor infiltrating lymphocytes and poor response to neoadjuvant chemotherapy in triple negative breast cancer (TNBC). Further study showed that inhibition of MAPK pathway with a MEK inhibitor is synergistic with anti-PD1/PD-L1 therapies. Methods: Patients with unresectable locally advanced or metastatic TNBC with ≤ 3 prior lines of therapy without prior anti-PD-1/PD-L1/PD-L2 therapies were enrolled. Treatment was started with a 2-week run in period with single agent binimetinib. Dose level 0 was binimetinib at 45 mg oral twice daily continuously and dose level -1 was 30 mg twice daily. Pembrolizumab was given at a fixed dose of 200 mg every 3 weeks at both dose levels. Phase I study was based on the standard 3+3 design. Results: A total of 12 patients were enrolled and treated in the phase 1. Five patients were enrolled at dose level 0, 1 patient withdrew prior to treatment and 1 patient was not evaluable for dose limiting toxicity (DLT). Among 3 evaluable patients, 2 patients experienced DLT with grade 3 flank pain and ALT abnormality. Additional 8 patients were enrolled at dose level -1. Out of 6 evaluable patients for DLT, there was 1 DLT observed with grade 3 AST and ALT abnormality. However, this particular patient had liver metastasis with grade 1 AST and ALT abnormality at baseline and her liver function test (LFT) normalized in 3 weeks after treatment discontinuation and oral prednisone. Other grade 1-2 common AEs included rash, LFT increase, abdominal pain, mucositis, nausea, cardiac troponin T increase without EKG change. The efficacy data will be presented at the meeting after the phase II interim analysis. Conclusions: Pembrolizumab in combination with binimetinib at 30 mg twice daily appears to be safe based on the initial cohort. Phase II part is currently ongoing with binimetinib 30 mg twice daily and pembrolizumab 200 mg every 3 weeks with a total of 23 patients planned where the safety and efficacy of this combination will be further evaluated. Clinical trial information: NCT03106415.
Chemotherapy-induced neutropenia with FOLFOX in the adjuvant treatment of colorectal cancer.
Authors: Joanna Gotfrit, Horia Marginean, Jean Alfred Maroun, Sara Trincao-Batra, Timothy R. Asmis, Michael M. Vickers, Rachel Anne Goodwin
Journal: Journal of Clinical Oncology (2020)

38 Background: Patients undergoing adjuvant treatment with FOLFOX for colorectal cancer (CRC) are at risk of developing chemotherapy-induced neutropenia (CIN). We assessed the risk of CIN and the use of granulocyte colony stimulating factor (GCSF). Methods: We performed a retrospective chart review of patients with CRC treated with FOLFOX at our institution from 2013 - 2015. Demographic and treatment data were collected. CIN was defined as ANC &lt;1.5, and all episodes of neutropenia were assumed to be the result of chemotherapy. Results: A total of 302 patients were included (baseline demographics in Table). In the overall cohort, 174 (58%) of patients had at least 1 episode of CIN. The risk CIN was 47% in stage II, 60% in low risk stage III (T1-3 and N1), and 58% in high risk stage III (T4 or N2). Among patients with at least 1 episode of CIN, the 1st CIN event occurred during the 1st 3 months of treatment in 76%, and the median cycle of 1st occurrence was 4 (95% CI 4-5), which did not differ by stage. Among patients who had at least 1 episode of CIN, 112 (64%) had a 2nd episode at a median cycle of 9 (95% CI 8-10). Among patients with at least 1 episode of CIN, 79 (45%) received subsequent GCSF, initiated 1 cycle after the 1st CIN event 37% of the time. Among patients with at least 2 episodes of CIN (n=112), 58 (52%) received GCSF after the 1st or 2nd event. Of these, 40 patients (69%) started GCSF newly after the 2nd CIN event. Among patients starting GCSF after the 2nd CIN event, 47% initiated GCSF 1 cycle later. The median cycle at which the relative dose intensity of FOLFOX decreased to &lt;85% was cycle 6 (95% CI 5-8) in those with no CIN events, cycle 3 (95% CI 2-4) in those with at least 1 CIN event treated with GCSF, and cycle 5 (95% CI 4-6) in those with at least 1 CIN event treated without GCSF. Conclusions: CIN is a frequent occurrence during the adjuvant treatment of CRC with FOLFOX and most often occurs in the first 3 months of treatment. While oncologists may treat some patients with 3 months of FOLFOX rather than 6, physicians must be aware of CIN regardless of the planned duration of treatment. Early initiation of GCSF may be a consideration. [Table: see text]
Validation of a Hematopoietic Cell Transplant-Composite Risk (HCT-CR) Model for Post-Transplant Survival Prediction in Patients with Hematologic Malignancies
Authors: Stefan O. Ciurea, Piyanuch Kongtim, Omar Hasan, Jorge M. Ramos Perez, Janet Torres, Gabriela Rondon, Richard E. Champlin
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Allogeneic hematopoietic stem cell transplantation (AHCT) outcomes depend on disease and patient characteristics. We previously developed a novel prognostic model, hematopoietic cell transplant composite-risk (HCT-CR) by incorporating the refined disease risk index (DRI-R) and hematopoietic cell transplant–comorbidity/age index (HCT-CI/Age) to predict post-transplant survival in patients with acute myeloid leukemia and myelodysplastic syndrome. Here we aimed to validate and prove the generalizability of the HCT-CR model in an independent cohort of patients with hematologic malignancies receiving AHCT. Experimental Design: Data of consecutive adult patients receiving AHCT for various hematologic malignancies were analyzed. Patients were stratified into four HCT-CR risk groups. The discrimination, calibration performance, and clinical net benefit of the HCT-CR model were tested. Results: The HCT-CR model stratified patients into four risk groups with significantly different overall survival (OS). Three-year OS was 67.4%, 50%, 37.5%, and 29.9% for low, intermediate, high, and very high-risk group, respectively (P &amp;lt; 0.001). The HCT-CR model had better discrimination on OS prediction when compared with the DRI-R and HCT-CI/Age (C-index was 0.69 vs. 0.59 and 0.56, respectively, P &amp;lt; 0.001). The decision curve analysis showed that HCT-CR model provided better clinical utility for patient selection for post-transplant clinical trial than the “treat all” or “treat none” strategy and the use of the DRI-R and HCT-CI/Age model separately. Conclusions: The HCT-CR can be effectively used to predict post-transplant survival in patients with various hematologic malignancies. This composite model can identify patients who will benefit the most from transplantation and helps physicians in making decisions regarding post-transplant therapy to improve outcomes.
Abdominal obesity and risk for esophageal cancer: A nationwide population-based cohort study of South Korea.
Authors: Dong Ho Lee, Jae Ho Cho, Cheol Min Shin, Kyungdo Han, Hyuk Yoon, Young Soo Park, Nayoung Kim
Journal: Journal of Clinical Oncology (2020)

446 Background: The relationship between overall obesity, as measured by body mass index (BMI), and risk of esophageal squamous cell carcinoma (ESCC) has been reported, and it has a negative correlation. However, the relationship with abdominal obesity, as measured by waist circumference, may be different. We investigated the association between abdominal obesity and ESCC. Methods: Retrospective cohort study with 22,809,722 individuals who had undergone regular health check-ups provided by the National Health Insurance Corporation between 2009 and 2012 (median follow-up period was 6.4 years) in South Korea. Abdominal obesity was defined as a waist circumference over 90 cm for men and 85 cm for women. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Chi-squared test and Cox proportional hazard model adjusted for confounding factors. Primary outcome was newly developed esophageal cancer. Results: After adjusting for BMI, abdominal obesity increased the risk of ESCC (HR 1.29, 95% CI 1.23–1.36). Waist circumference is associated with increased risk of ESCC in a dose-dependent manner ( P for trend &lt; 0.0001). We analyzed individuals divided into five categories of BMI. Among individuals with overweight (BMI 23–24.9 kg/m 2 ) and obese I (BMI 25–29.9 kg/m 2 ), abdominal obesity was a risk factor associated with developing ESCC (HR 1.22, 95% CI 1.11–1.34; HR 1.28, 95% CI 1.18–1.39, respectively). Conclusions: Abdominal obesity, not BMI itself, is associated with an increased risk for ESCC. Therefore, reducing abdominal obesity may affect decreasing the development of ESCC.
Circulating IL-8 levels as candidate marker of antiangiogenic therapy for metastatic colorectal cancer.
Authors: Mitsukuni Suenaga, Tetsuo Mashima, Naomi Kawata, Takeru Wakatsuki, Hiroyuki Seimiya, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2020)

172 Background: Liver metastasis (LM) confers poor prognosis in metastatic colorectal cancer (mCRC). It has not been well understood whether tumor microenvironment (TM) varies throughout cancer treatment in the presence of LM. We therefore investigated the difference of TM between first-line (FL) and savage-line (SL) anti-angiogenic therapies and tested whether specific angiogenic cytokines could predict clinical outcome in mCRC patients. Methods: A combined cohort consisting of two cohorts (N = 125) was included in this study: 71 patients received first-line treatment with bevacizumab (FL cohort: median age, 60; median follow-up, 28.9 mos) and 54 patients received salvage-line regorafenib (SL cohort: median age, 65; median follow-up, 17.2 mos). Blood samples were obtained from all patients at baseline (BL) and during the treatment, and serum levels of nine angiogenic cytokines were measured using ELISA. Progression-free survival and overall survival (OS) were analyzed using Kaplan-Meier curves, log-rank test, and Cox proportional hazard regression. Results: In univariate analysis for the combined cohort, right-sided CRC, primary unresected, KRAS wild-type, LM, metastatic site ≥2 and SL were associated with shorter OS, and LM and SL remained in multivariable analysis. Ang-2 and IL-8 levels at BL were significantly associated with LM and their cut-off values were 2190.3 pg/ml (CO Ang2 ) and 15.1 pg/ml (CO IL8 ), respectively, and no significant interaction was shown between cytokines and cohorts. Patients with Ang-2 levels ≥CO Ang2 had shorter OS than those with Ang-2 levels &lt; CO Ang2 (HR2.57, 95%CI: 1.47–4.51, P = 0.001), while IL-8 levels ≥CO IL8 was associated with shorter OS than &lt; CO IL8 (HR4.31, 95%CI: 2.11–8.79, P &lt; 0.001). IL-8 levels ≥CO IL8 remained as significant in multivariable analysis (HR 3.24, 95%CI: 1.47–7.16, P = 0.004). In change analysis, there was no significant correlation of variation of IL-8 and Ang-2 levels with clinical outcome after the first treatment cycle in both cohorts. Conclusions: Circulating IL-8 and Ang-2 levels reflect the TM in the presence of LM, of which IL-8 may serve as solid prognostic marker of anti-angiogenic therapy regardless of the timing of treatment for mCRC.
Predictors of immunotherapy (IO) response in hepatocellular carcinoma (HCC).
Authors: Samantha Ann Armstrong, Bhavana Pendurthi Singh, Monika Kulasekaran, Petra Prins, Aiwu Ruth He
Journal: Journal of Clinical Oncology (2020)

555 Background: Despite advances in understanding the molecular pathways of HCC, therapeutic options are limited and patient survival is dismal. IO is a promising HCC treatment. There are currently no indicators to identify which patients (pts) will have a prolonged response. Methods: In this single-institutional retrospective analysis, pts received one of five IO containing regimens with nivolumab, pembrolizumab, atezolizumab plus bevacizumab, durvalumab or cemiplimab until disease progression (PD) or unacceptable toxicity. Relevant factors including: stage, viral etiology, vascular invasion (VI), tumor thrombus (TT), multifocal disease, toxicity grade, steroid use for IO mediated toxicities and derived Neutrophil-to Lymphocyte ratio (dNLR), were correlated to clinical outcome: progression free survival (PFS), overall survival (OS), response rate (RR), using Pearson’s chi-square test or student's t-test . Responses were assessed using RECIST v 1.1 criteria for stable disease (SD), partial response (PR) and PD were correlated with best response and PFS. OS was calculated by the Kaplan-Meier method. Results: Cohort demographics (n = 76) were: 72% male; 38% African American, 30% Caucasian and 16% Asian; 29% of pts had HBV, 41% had HCV, 1% had both HBV/HCV and 13% had no viral etiology (n = 64). The majority of pts were stage III (43%) or IV (38%). At the start of IO, 32% had VI, 32% had TT and 80% had multifocal or metastatic disease. 65% of pts experienced IO toxicity, with 24.3% at grade 3 or higher, and 34% requiring steroids. Best response to IO was SD in 65.7% of pts, PR in 25.7% and PD in 8.6%. Median OS was 13m (95% CI 7.9-18.1) from the start of IO and median PFS (n = 65) was 14m (95% CI 6.8-21.2). Median OS and PFS were significantly improved in pts with PR compared to PD (45 vs 8m, p &lt; 0.0005, PFS 15 vs 3m p = 0.007). Both OS and PFS showed benefits for SD of ≥2 months compared to those with PD (11 vs 8m, p &lt; .0005, PFS 5 vs 3m p = .007). VI, TT, stage, viral etiology, toxicity grade or dNLR did not correlate with OS, PFS and RR, however need of steroid treatment trended toward worse outcome. Conclusions: PR and SD are independent predictors for prolonged PFS and OS in HCC pts receiving IO therapy. Absence of steroid use for toxicity trended toward improved IO response.
Rural-urban disparities in colorectal cancer screening: An insight from a statewide database.
Authors: Renugadevi Swaminathan, James D. Morris, Terry C. Davis
Journal: Journal of Clinical Oncology (2020)

69 Background: The Healthy People 2020 initiative aims to increase colorectal cancer (CRC) screening. The common CRC screening options are FIT, FOBT, sigmoidoscopy, and colonoscopy. Colonoscopy allows visualization of the entire colon and offers therapeutic benefit whereas stool tests are less invasive, cost-effective and are easily available. Inequities exist in CRC screening among rural residents which may be contributed to a lower level of education, income, health insurance and access to health care. The purpose of the study is to identify the impact of geographic region on the preference of CRC screening modality among Louisiana adults. Methods: We performed a retrospective cohort study among age-eligible Louisiana adults who had CRC screening either with colonoscopy or stool-based tests using the 2016 Behavioral Risk Factor Surveillance System database (n = 1372). We examined demographic characteristics among participants who had CRC screening with colonoscopy versus who had a stool-based test. Multivariable logistic regression analysis evaluated the association of geographic region and the preference of CRC screening. Results: Participants age 65-75 years old were 36% less likely to have a colonoscopy as compared to age 50-64 years (p = 0.0008). African Americans and Hispanic Americans were 34% (p &lt; 0.006) and 55% (p = 0.057) less likely to have a colonoscopy as compared to Caucasian Americans, respectively. Medicaid and Medicare participants were 82% (p &lt; 0.0001) and 52% (p &lt; 0.0001) less likely to have a colonoscopy compared to participants with private insurance, respectively. After adjusting for age, race/ethnicity, education, income, and insurance the odds of screening colonoscopy was 29% lower for rural residents compared to urban residents of Louisiana (OR 0.71 95% CI 0.53 - 0.94). Conclusions: Individuals residing in rural parishes of Louisiana were more likely to have a stool-based test for CRC screening. Health care providers while considering the reliability and feasibility of CRC screening modality should also incorporate patient’s preferences while offering the screening tests to increase the rate of CRC screening.
Real World Use of Hypertonic Saline in Refractory Acute Decompensated Heart Failure
Authors: Matthew Griffin, Aaron Soufer, Erden Goljo, Matthew Colna, Veena S. Rao, Sangchoon Jeon, Parinita Raghavendra, Julie D’Ambrosi, Ralph Riello, Steven G. Coca, Devin Mahoney, Daniel Jacoby, Tariq Ahmad, Michael Chen, W.H. Wilson Tang, Jeffrey Turner, Wilfried Mullens, Francis P. Wilson, Jeffrey M. Testani
Journal: JACC Heart Failure (2020)