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Vlad Sandulache, Anita Sabichi, George Chen, and Scott Charnitsky

Background: The Veterans Health Administration (VHA) is the only nationally integrated healthcare delivery system in the United States. The vertical and horizontal integration of the VHA make it an ideal environment for development of tools designed to streamline cancer diagnosis and treatment. Head and neck cancer (HNC) remains a difficult disease to diagnose and treat. Delivery of multimodality treatment for advanced HNC is challenging at both academic centers and in the community setting. This problem is magnified by the increased incidence of HNC, powered by an epidemic increase in the incidence of human papilloma virus (HPV)–associated oropharyngeal cancer (OPC). Objective: To develop a non–resource-intensive approach to improving: (1) time to treatment initiation and (2) compliance with optimal treatment package time for HNC patients. Methods: Retrospective analysis of 300 patients with a diagnosis of HNC from the Michael E. DeBakey VA Medical Center (MEDVAMC) was used to generate baseline data (2000–2010) for: (1) time to treatment (surgery, 24 days; radiation, 48 days) and (2) treatment package time <100 days compliance (68%). We developed a tool available to providers and clinic staff to prospectively track patients from initial referral, through diagnosis and treatment, along with completion of ancillary studies (modified barium swallow) and completion of the survivorship care plan. Between June 2016 and October 2018, 350 patients were tracked using this tool; 275 patients were new HNC diagnoses. Results: Implementation of the tracking tool reduced diagnosis to treatment start (mean, 44 days; median, 26 days). Compliance with treatment package time <100 days was increased to 95%; compliance with initiation of adjuvant radiation within 6 weeks of surgery was increased to 75%. Utilization of the tool allowed for streamlined surgical care, particularly through integration of dental extractions into the oncologic resection, and facilitated timely initiation of adjuvant radiation for advanced HNC. Conclusions: It is possible to improve: (1) time to diagnosis, (2) time to treatment initiation, and (3) treatment completion rates for complex HNC requiring multimodality treatment without additional resource utilization. However, appropriate implementation requires a robust multidisciplinary treatment team, with appropriate “buy in” from all participants and is facilitated by the presence of a fully integrated health care delivery system.

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Potjana Jitawatanarat, Arpita Desai, Pradeep Sharda, Hong Liu, Maureen Ross, Francisco J. Hernandez-llizaliturri, Philip L. McCarthy, and George L. Chen

This case report presents a patient with poor-prognosis chronic lymphocytic leukemia (CLL) who was treated with chemotherapy and underwent allogeneic hematopoietic cell transplant (alloHCT) but ultimately progressed. The application of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL and the impact of alloHCT on secondary therapy for progressive CLL are discussed.

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Luxi Chen, John Davelaar, Srinivas Gaddam, Kambiz Kosari, Nicholas Nissen, George Chaux, Christopher Lee, Eric Vail, Andrew Hendifar, Jun Gong, Karen Reckamp, and Arsen Osipov

Pancreatic metastasis of primary lung adenocarcinoma is a rare occurrence, accounting for <0.3% of all pancreatic malignancies. Given that the prognosis and treatment options for primary pancreatic cancer differ greatly from pancreatic metastases from a primary site, an accurate diagnosis is critical. This report presents a unique case of a 65-year-old man who was admitted with significant unintentional weight loss, fatigue, abdominal pain, and jaundice, and found to have a pancreatic mass initially thought to be primary pancreatic adenocarcinoma and subsequently diagnosed as an EGFR-mutated lung adenocarcinoma with metastases to the pancreas via early application of next-generation sequencing (NGS). The use of NGS early in the patient’s clinical course not only changed the treatment strategy but also drastically altered the prognosis. Although metastatic pancreatic adenocarcinoma has a poor prognosis and survival rate, treatment of EGFR-mutated non–small cell lung cancer with EGFR tyrosine kinase inhibitors is associated with high response rates. Importantly, our case demonstrates that timely application of NGS very early in the disease course is paramount to the diagnosis, management, and prognosis of solid malignancies.

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Eric Lu, George V. Thomas, Yiyi Chen, Alexander W. Wyatt, Paul Lloyd, Jack Youngren, David Quigley, Raymond Bergan, Shawna Bailey, Tomasz M. Beer, Felix Y. Feng, Eric J. Small, and Joshi J. Alumkal

Background: PARP inhibition is a promising therapeutic strategy for the treatment of men with metastatic castration-resistant prostate cancer whose tumors harbor homologous recombination DNA repair gene alterations. However, questions remain for many practicing clinicians about which patients are ideally suited for PARP inhibitor treatment. This report details our institutional experience using PARP inhibitor therapy in patients whose tumors harbored specific DNA repair gene alterations. Patients and Methods: We performed a retrospective chart review to identify patients at Oregon Health & Science University who were treated with PARP inhibition. We identified 8 patients and determined the impact of the specific DNA repair gene alterations on tumor response and time on treatment with PARP inhibition. Results: A number of DNA repair gene alterations were identified. Three patients had pathogenic BRCA2 mutations and one had a BRCA2 mutation of uncertain significance. Conversely, the 4 other patients' tumors harbored alterations in other DNA repair genes, none of which were clearly pathogenic. A statistically significant difference in benefit was seen between patients whose tumors harbored BRCA2 gene alterations and those whose tumors did not, as measured by >50% decline in prostate-specific antigen levels (100% vs 0%; P=.03) and duration on therapy (31.4 vs 6.4 weeks; P=.03). Conclusions: Our results demonstrate that not all DNA repair alterations are equally predictive of PARP inhibitor response. Importantly, all responding patients had tumors harboring BRCA2 DNA repair alterations, including one without a known pathogenic mutation. Conversely, among the 4 nonresponders, several DNA repair alterations in genes other than BRCA2 were identified that were not clearly pathogenic. This demonstrates the need to carefully examine the functional relevance of the DNA repair alterations identified, especially in genes other than BRCA2, when considering patients for PARP inhibitor treatment.

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Yifan Wang, Adeline Cuggia, Yen-I Chen, Josée Parent, Agatha Stanek, Robert E. Denroche, Amy Zhang, Robert C. Grant, Céline Domecq, Bryn Golesworthy, Chaya Shwaartz, Ayelet Borgida, Spring Holter, Julie M. Wilson, George Chong, Grainne M. O’Kane, Jennifer J. Knox, Sandra E. Fischer, Steven Gallinger, Zu-Hua Gao, William D. Foulkes, Kevin A. Waschke, and George Zogopoulos

Background: Individuals with a family history of pancreatic adenocarcinoma (PC) or with a germline mutation in a PC susceptibility gene are at increased risk of developing PC. These high-risk individuals (HRIs) may benefit from PC surveillance. Methods: A PC surveillance program was developed to evaluate the detection of premalignant lesions and early-stage PCs using biannual imaging and to determine whether locally advanced or metastatic PCs develop despite biannual surveillance. From January 2013 to April 2020, asymptomatic HRIs were enrolled and followed with alternating MRI and endoscopic ultrasound every 6 months. Results: Of 75 HRIs, 43 (57.3%) had a germline mutation in a PC susceptibility gene and 32 (42.7%) had a familial pancreatic cancer (FPC) pedigree. Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) were identified in 26 individuals (34.7%), but only 2 developed progressive lesions. One patient with Peutz-Jeghers syndrome (PJS) developed locally advanced PC arising from a BD-IPMN. Whole-genome sequencing of this patient’s PC and of a second patient with PJS-associated PC from the same kindred revealed biallelic inactivation of STK11 in a KRAS-independent manner. A review of 3,853 patients from 2 PC registries identified an additional patient with PJS-associated PC. All 3 patients with PJS developed advanced PC consistent with the malignant transformation of an underlying BD-IPMN in <6 months. The other surveillance patient with a progressive lesion had FPC and underwent resection of a mixed-type IPMN that harbored polyclonal KRAS mutations. Conclusions: PC surveillance identifies a high prevalence of BD-IPMNs in HRIs. Patients with PJS with BD-IPMNs may be at risk for accelerated malignant transformation.

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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.

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Ayman Saad, Alison Loren, Javier Bolaños-Meade, George Chen, Daniel Couriel, Antonio Di Stasi, Areej El-Jawahri, Hany Elmariah, Sherif Farag, Krishna Gundabolu, Jonathan Gutman, Vincent Ho, Rasmus Hoeg, Mitchell Horwitz, Joe Hsu, Adetola Kassim, Mohamed Kharfan Dabaja, John Magenau, Thomas Martin, Marco Mielcarek, Jonathan Moreira, Ryotaro Nakamura, Yago Nieto, Cameron Ninos, Caspian Oliai, Seema Patel, Brion Randolph, Mark Schroeder, Dimitrios Tzachanis, Asya Nina Varshavsky-Yanovsky, Madhuri Vusirikala, Frankie Algieri, and Lenora A. Pluchino

The NCCN Guidelines for Hematopoietic Cell Transplantation (HCT) provide an evidence- and consensus-based approach for the use of autologous and allogeneic HCT in the management of malignant diseases in adult patients. HCT is a potentially curative treatment option for patients with certain types of malignancies; however, recurrent malignancy and transplant-related complications often limit the long-term survival of HCT recipients. The purpose of these guidelines is to provide guidance regarding aspects of HCT, including pretransplant recipient evaluation, hematopoietic cell mobilization, and treatment of graft-versus-host disease—a major complication of allogeneic HCT—to enable the patient and clinician to assess management options in the context of an individual patient’s condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for HCT, including the incorporation of a newly developed section on the Principles of Conditioning for HCT.