Identifying Clinical Factors Which Predict for Early Failure Patterns Following Resection for Pancreatic Adenocarcinoma in Patients Who Received Adjuvant Chemotherapy Without Chemoradiation

Objectives: The role of radiation therapy (RT) in resected pancreatic cancer (PC) remains incompletely defined. We sought to determine clinical variables which predict for local-regional recurrence (LRR) to help select patients for adjuvant RT. Materials and Methods: We identified 73 patients with PC who underwent resection and adjuvant gemcitabine-based chemotherapy alone. We performed detailed radiologic analysis of first patterns of failure. LRR was defined as recurrence of PC within standard postoperative radiation volumes. Univariate analyses (UVA) were conducted using the Kaplan-Meier method and multivariate analyses (MVA) utilized the Cox proportional hazard ratio model. Factors significant on UVA were used for MVA. Results: At median follow-up of 20 months, rates of local-regional recurrence only (LRRO) were 24.7%, LRR as a component of any failure 68.5%, metastatic recurrence (MR) as a component of any failure 65.8%, and overall disease recurrence (OR) 90.5%. On UVA, elevated postoperative CA 19-9 (>90 U/mL), pathologic lymph node positive (pLN+) disease, and higher tumor grade were associated with increased LRR, MR, and OR. On MVA, elevated postoperative CA 19-9 and pLN+ were associated with increased MR and OR. In addition, positive resection margin was associated with increased LRRO on both UVA and MVA. Conclusions: About 25% of patients with PC treated without adjuvant RT develop LRRO as initial failure. The only independent predictor of LRRO was positive margin, while elevated postoperative CA 19-9 and pLN+ were associated with predicting MR and overall survival. These data may help determine which patients benefit from intensification of local therapy with radiation. Supported by the following grants: Award Number Grant KL2TR001068 from the National Center for Advancing Translational Sciences, and NIH R01 CA198128 (T.M.W.). Presented at the American Society of Radiation Oncology (ASTRO) Annual Meeting, 2015, San Antonio, TX. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. The authors declare no conflicts of interest. Reprints: Terence M. Williams, MD, PhD, Department of Radiation Oncology, The Ohio State University, 460 W. 12th Avenue, Columbus, OH 43210. E-mail: terence.williams@osumc.edu. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Routine Adaptive Replanning of p16-Positive Stage N2b Oropharyngeal Cancer: Quality Improvement or Waste of Time?

Purpose/Objective(s): To determine if routinely replanning patients treated for oropharyngeal cancer that is p16-positive and clinical neck stage N2b (AJCC 7th edition) is likely to result in dose changes that will improve patient outcomes to a meaningful degree. Methods: In 10 consecutive patients treated with primary radiotherapy (RT) and concurrent weekly chemotherapy for p16-positive N2b oropharyngeal carcinoma, we prospectively evaluated dose changes from replanning for the final 4 or 2 weeks of RT of a 7-week RT program. Results: Replanning for the final 4 or 2 weeks improved planning target volume coverage by an average of 4 and 2 percentage points, respectively. For all normal structures, the dose change was small (

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Nivolumab in the Treatment of Metastatic Renal Cell Carcinoma: A Cost-Utility Analysis

Introduction: Nivolumab improves overall survival and health-related quality of life compared with everolimus in metastatic renal cell carcinoma (mRCC). This study assesses the cost-utility of nivolumab from the Canadian health care payer perspective. Materials and Methods: To evaluate the cost-utility of nivolumab, a Markov cohort model that incorporated data from the phase 3 CheckMate-025 trial and other sources was developed. The incremental cost per quality-adjusted life month (QALM) gained for nivolumab was calculated. A lifetime horizon was used in the base-case with costs and outcomes discounted 3% annually. The probabilities of progression and death from cancer and utility values were captured from the CheckMate-025 trial. Expected costs were based on Ontario fees and other sources. Scenario and sensitivity analyses were conducted to assess uncertainty. Results: Compared with everolimus, nivolumab provided an additional 4.2 QALM at an incremental cost of $34,153. The resulting incremental cost-effectiveness ratio was $8138/QALM gained. Assuming a willingness to pay (WTP) threshold of $4167/QALM ($50,000/quality-adjusted life-year [QALY]), nivolumab was not cost-effective. In 1-way sensitivity analyses, nivolumab cost, median overall survival, and median treatment duration were sensitive to changes. Furthermore, the results were sensitive to the WTP threshold and nivolumab became a cost-effective strategy with a WTP of $8333/QALM ($100,000/QALY). Conclusions: Compared with everolimus, nivolumab is unlikely to be cost-effective for the treatment of mRCC from a Canadian health care perspective with its current price assuming a WTP of $50,000/QALY. Although mRCC patients derive a meaningful clinical benefit from nivolumab, considerations should be given to avoid drug wastage and increase the WTP threshold to render this strategy more affordable. The authors declare no conflicts of interest. Reprints: Jacques Raphael, MSc, MD, Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Toronto, ON, Canada, M5T 3M6. E-mail: raphaeljack13@hotmail.com. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The University of Florida Department of Radiation Oncology Guidelines for Treatment of Differentiated Thyroid Cancer With I-131 or External-beam Radiotherapy

The purpose of this paper is to summarize the University of Florida Department of Radiation Oncology guidelines for treatment of differentiated thyroid cancer with I-131 or external-beam radiotherapy. This article is not meant to compete with the many excellent book chapters and consensus guidelines that present comprehensive discussions of treatment options. This is a streamlined, "How we do it?" reference without substantial discussion of background or supporting data. To serve as a treatment reference, the great majority of the information is presented in topic-specific tables. The authors declare no conflicts of interest. Reprints: Robert J. Amdur, MD, 2000 SW Archer Road, P.O. Box 100385, Gainesville, FL 32610-0385. E-mail: amdurr@shands.ufl.edu. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Rectal Culture and Sensitivity Analysis for Reducing Sepsis Risk After Fiducial Marker Placement

Purpose: Placement of fiducial markers for prostate radiotherapy (RT) is associated with a 2% to 3% risk of bacterial urinary tract infection (UTI) that may progress to sepsis necessitating hospitalization. These bacterial UTIs are primarily due to flouroquinolone (FQ) resistant Escherichia coli (E. coli). The incidence of this complication has increased in recent years. The purpose of this study is to determine whether rectal culture and sensitivity (C&S) to identify FQ resistant E. coli obtained before placement of fiducial markers for prostate RT reduces the likelihood of this complication. Methods: In total, 412 patients treated with RT at the University of Florida Proton Therapy Institute between 2015 and 2017 were included in the study. Rectal C&S were obtained at the time of initial consultation which preceded placement of fiducial markers for planning and realignment for prostate RT. Patients in whom resistant E. coli were identified had their prophylactic antibiotic regimen modified accordingly. Whether bacterial UTI requiring hospitalization following fiducial placement occurred was prospectively recorded in the medical record on the first day of RT. Results: One of 412 patients (0.2%) developed bacterial sepsis requiring hospitalization after fiducial placement. Conclusion: Rectal C&S to identify FQ resistant E. coli before placement of fiducial markers for prostate RT likely reduces the risk of bacterial UTI necessitating hospitalization. The authors declare no conflicts of interest. Reprints: William M. Mendenhall, MD, 2000 SW Archer Rd, P. O. Box 100385, Gainesville, FL 32610-0385. E-mail: mendwm@shands.ufl.edu. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Corrigendum to “Endoscopic resection with adjuvant chemo-radiotherapy for superficial esophageal squamous cell carcinoma: A critical review” [Crit. Rev. Oncol./Hematol. 124, April (2018), 61–65]

Publication date: Available online 4 May 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Tsz Yeung Kam, Melpomeni Kountouri, Arnaud Roth, Jean-Louis Frossard, Olivier Huber, Stefan Mönig, Thomas Zilli




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Chimeric antigen receptor T cell therapy in pancreatic cancer: from research to practice

Abstract

Chimeric antigen receptor (CAR) T cell therapy is genetically engineered tumor antigen-specific anticancer immunotherapy, which after showing great success in hematological malignancies is currently being tried in advanced solid tumors like pancreatic cancer. Immunosuppressive tumor microenvironment and dense fibrous stroma are some of the limitation in the success of this novel therapy. However, genetic modifications and combination therapy is the topic of the research to improve its efficacy. In this article, we summarize the current state of knowledge, limitations, and future prospects for CAR T cell therapy in pancreatic cancer.

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