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Puyao C. Li and Rinaa S. Punglia
Jordan M. Cloyd, Chengli Shen, Heena Santry, John Bridges, Mary Dillhoff, Aslam Ejaz, Timothy M. Pawlik and Allan Tsung
Background: Current guidelines support either immediate surgical resection or neoadjuvant therapy (NT) for patients with resectable pancreatic ductal adenocarcinoma (PDAC). However, which patients are selected for NT and whether disparities exist in the use of NT for PDAC are not well understood. Methods: Using the National Cancer Database from 2004 through 2016, the clinical, demographic, socioeconomic, and hospital-related characteristics of patients with stage I/II PDAC who underwent immediate surgery versus NT followed by surgery were compared. Results: Among 58,124 patients who underwent pancreatectomy, 8,124 (14.0%) received NT whereas 50,000 (86.0%) did not. Use of NT increased significantly throughout the study period (from 3.5% in 2004 to 26.4% in 2016). Multivariable logistic regression analysis showed that travel distance, education level, hospital facility type, clinical T stage, tumor size, and year of diagnosis were associated with increased use of NT, whereas comorbidities, uninsured/Medicaid status, South/West geography, left-sided tumor location, and increasing age were associated with immediate surgery (all P<.001). Based on logistic regression–derived interaction factors, the association between NT use and median income, education level, Midwest location, clinical T stage, and clinical N stage significantly increased over time (all P<.01). Conclusions: In addition to traditional clinicopathologic factors, several demographic, socioeconomic, and hospital-related factors are associated with use of NT for PDAC. Because NT is used increasingly for PDAC, efforts to reduce disparities will be critical in improving outcomes for all patients with pancreatic cancer.
Saranya Chumsri, Ethan S. Sokol, Aixa E. Soyano-Muller, Ricardo D. Parrondo, Gina A. Reynolds, Aziza Nassar and E. Aubrey Thompson
Increasing data support the importance of preexisting host immune response and neoantigen burden for determining response to immune checkpoint inhibitors (ICIs). In lung cancer and melanoma, tumor mutational burden (TMB) has emerged as an independent biomarker for ICI response. However, the significance of TMB in breast cancer, particularly in the context of PD-L1 negativity, remains unclear. This report describes a patient with HER2-negative breast cancer with high TMB and an apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) trinucleotide signature; her disease was refractory to multiple lines of treatments but achieved durable complete response using ICIs and capecitabine. Additional analysis of the tumor revealed a low amount of stromal tumor-infiltrating lymphocytes (sTILs) and PD-L1 negativity, reflecting a poor preexisting host immune response. In collaboration with Foundation Medicine, comprehensive genomic profiling from 14,867 patients with breast cancer with the FoundationOne test was evaluated. Using the cutoff of ≥10 mutations/megabase (mut/Mb) for high TMB, PD-L1 positivity and TMB-high populations were not significantly overlapping (odds ratio, 1.02; P=.87). Up to 79% of TMB-high tumors with >20 mut/Mb were PD-L1–negative. Our study highlights that despite having low TILs and PD-L1 negativity, some patients may still experience response to ICIs.
Abraham S. Kanate, Miguel-Angel Perales and Mehdi Hamadani
Eligibility assessment of a potential candidate for allogeneic hematopoietic cell transplantation (allo-HCT) is a complex yet vital component of pretransplant evaluation. Although no formal standardized consensus exists to guide this process, transplant centers follow institutional standard operating procedures and parameters to approve candidacy of an individual patient. Consideration for allo-HCT is dependent on a myriad of interrelated factors, including disease-related (eg, appropriate indication, disease status, prior therapies), patient-related (eg, age, functional status, frailty, comorbidities), psychosocial, and economic factors. A multidisciplinary approach is optimal for patient selection and requires the efforts of transplant coordinators, nurses, advanced practice providers, social workers, psychologists, financial specialists, and physicians. This article reviews the data and provides general guidelines that may be used in making an informed decision when evaluating a prospective candidate for allo-HCT. These recommendations are based on published data, expert commentary, reviews, and institutional practices. In the end, the eligibility assessment and decision to consider allo-HCT as the optimal choice of treatment for an individual patient are truly as much an “art” as it is the “science” of medicine, encompassing a multidisciplinary approach to minimize harm without compromising the curative potential—all essential doctrines of the Hippocratic Oath.
Ayman Saad, Marcos de Lima, Sarah Anand, Vijaya Raj Bhatt, Ryan Bookout, George Chen, Daniel Couriel, Antonio Di Stasi, Areej El-Jawahri, Sergio Giralt, Jonathan Gutman, Vincent Ho, Mitchell Horwitz, Joe Hsu, Mark Juckett, Mohamed Kharfan Dabaja, Alison W. Loren, MSCE, Javier Meade, Marco Mielcarek, Jonathan Moreira, Ryotaro Nakamura, Yago Nieto, Julianna Roddy, Gowri Satyanarayana, Mark Schroeder, Carlyn Rose Tan, Dimitrios Tzachanis, Jennifer L. Burns and Lenora A. Pluchino
Hematopoietic cell transplantation (HCT) involves the infusion of hematopoietic progenitor cells into patients with hematologic disorders with the goal of re-establishing normal hematopoietic and immune function. HCT is classified as autologous or allogeneic based on the origin of hematopoietic cells. Autologous HCT uses the patient’s own cells while allogeneic HCT uses hematopoietic cells from a human leukocyte antigen-compatible donor. Allogeneic HCT is a potentially curative treatment option for patients with certain types of hematologic malignancies, and autologous HCT is primarily used to support patients undergoing high-dose chemotherapy. Advances in HCT methods and supportive care in recent decades have led to improved survival after HCT; however, disease relapse and posttransplant complications still commonly occur in both autologous and allogeneic HCT recipients. Allogeneic HCT recipients may also develop acute and/or chronic graft-versus-host disease (GVHD), which results in immune-mediated cellular injury of several organs. The NCCN Guidelines for Hematopoietic Cell Transplantation focus on recommendations for pretransplant recipient evaluation and the management of GVHD in adult patients with malignant disease.