Implementation of a standardized approach to borderline resectable pancreatic cancer in a multisite community oncology program.

BACKGROUND: Treatment paradigms for borderline resectable pancreatic cancer are evolving with increasing use of neoadjuvant chemotherapy and neoadjuvant chemoradiation. Variations in the definition of borderline resectable pancreatic cancer and neoadjuvant approaches have made standardizing care for borderline resectable pancreatic cancer difficult. We report an effort to standardize management of borderline resectable pancreatic cancer throughout Sanford Health, a large community oncology network. METHODS: Starting in October 2013, cases of pancreatic adenocarcinoma without known metastatic disease were categorized as borderline resectable pancreatic cancer if they met ≥ 1 of the following criteria: (1) abutment of superior mesenteric, common hepatic, or celiac arteries with < 180° involvement, (2) venous involvement deemed potentially suitable for reconstruction, and/or (3) biopsy-proven lymph node involvement. Patients with borderline resectable pancreatic cancer were treated with neoadjuvant chemotherapy followed by reimaging and surgery if venous involvement had improved; if disease remained borderline resectable, patients underwent neoadjuvant chemoradiation and surgical exploration as long as reimaging did not reveal evidence of progressive disease. RESULTS: Forty-three patients from October 2013 to April 2017 were diagnosed with borderline resectable pancreatic cancer. Twelve of 42 (29%) patients proceeded to surgical exploration directly after neoadjuvant chemotherapy; 23 (55%) received neoadjuvant chemoradiation. Overall, 28/43 (65%) underwent exploration with 19 (44%) able to undergo resection. Of those, 14/19 (74%) attained R0 resection and 11/19 (58%) were pathologic N0. No pretreatment or treatment variables were associated with resection rates; resection was the only variable associated with survival. CONCLUSION: This report demonstrates the feasibility of implementing a standardized approach to borderline resectable pancreatic cancer across multiple sites over a wide geographic area. Adherence to protocol therapies was good and surgical outcomes are similar to many reported series.

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study.

PURPOSE: Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC. PATIENTS AND METHODS: Eligible patients included those with oral cavity (excluding lip), oropharyngeal, hypopharyngeal, or laryngeal stage III to IVB HNSCC (according to American Joint Committee on Cancer, 7th edition, staging system) eligible for cisplatin-based, standard-dose (70 Gy) chemoradiotherapy. Pembrolizumab was administered concurrently with and after chemoradiotherapy with weekly cisplatin. Safety was the primary end point and was determined by incidence of chemoradiotherapy adverse events (AEs) and immune-related AEs (irAEs). Efficacy was defined as complete response (CR) rate on end-of-treatment (EOT) imaging or with pathologic confirmation at 100 days postradiotherapy completion. Key secondary end points included overall (OS) and progression-free survival (PFS). RESULTS: The study accrued 59 patients (human papillomavirus [HPV] positive, n = 34; HPV negative, n = 25) from November 2015 to October 2018. Five patients (8.8%) required discontinuation of pembrolizumab because of irAEs, all of which occurred during concurrent chemoradiotherapy; 98.3% of patients completed the full planned treatment dose (70 Gy) of radiotherapy without any delays ≥ 5 days; 88.1% of patients completed the goal cisplatin dose of ≥ 200 mg/m2. EOT CR rates were 85.3% and 78.3% for those with HPV-positive and -negative HNSCC, respectively. CONCLUSION: Pembrolizumab in combination with weekly cisplatin-based chemoradiotherapy is safe and does not impair delivery of curative radiotherapy or chemotherapy in HNSCC. Early efficacy data support further investigation of this approach.

Delivering Precision Oncology in a Community Cancer Program: Results From a Prospective Observational Study.

INTRODUCTION: Precision oncology (PO) is a growing treatment approach in the era of next-generation sequencing (NGS) and matched therapies. Effective delivery of PO in the community has not been extensively studied. Our program developed a virtual molecular tumor board (MTB) strategy to help guide PO care. MATERIALS AND METHODS: Over 18 months, eligible adult patients with advanced, incurable solid tumor malignancies were enrolled in a molecular profiling (MP) study using the Foundation Medicine NGS panel. Results were reviewed through a weekly, videoconferenced MTB conducted across our largely rural integrated health system. Recommendations from the MTB were used to identify actionable alterations (AAs). Feasibility of PO care delivery was assessed as the primary outcome. Secondary outcomes included the frequency of AAs, genomic matched treatments, genomic matched clinical trial enrollment, and clinical outcomes. RESULTS: A total of 120 participants with a variety of advanced tumor types were enrolled. Of these, 109 (90.8%) had successful MP. Treatment on the basis of an AA was recommended by the MTB in 58% of patients (63 of 109) who had a successful MP result. For those completing MP, treatments included enrollment in a genomic matched clinical trial (n = 16; 14.6%) and genomic matched treatment with a Food and Drug Administration-approved agent (n = 23; 21.1%). Response and survival data were similar regardless of the matched treatment option chosen. CONCLUSION: A video-conferenced MTB-facilitated NGS testing and treatment delivery system was implemented in our integrated community oncology program. Continued use of this model aims to increase understanding of the impact of PO in this setting.

Heparin-induced thrombocytopenia.

Heparin-Induced Thrombocytopenia (HIT) is a well recognized, potentially life-threatening, complication of heparin therapy. It is associated with an increased risk of thrombosis which can be sometimes fatal. Making the diagnosis of HIT can be quite challenging for the clinician as it requires recognition of the tell-tale clinical presentation as well as positive confirmation with appropriate laboratory diagnostic tests. This paper reviews the pathophysiology, recognition, treatment and prevention of HIT for the clinical physician.