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.

Fractionated stereotactic radiation therapy for vestibular schwannomas: Dosimetric factors predictive of hearing outcomes.

PURPOSE: To determine dosimetric factors predictive of hearing loss in vestibular schwannoma (VS) patients treated with definitive fractionated stereotactic radiation therapy (FSRT), and to report tumor control, serviceable hearing preservation, and cranial nerve toxicities. METHODS AND MATERIALS: We identified 45 patients (29 men and 16 women) with unilateral sporadic VS, who underwent definitive FSRT. All patients had serviceable hearing prior to treatment, defined as Gardner-Robertson Class 1 or 2. All patients underwent an audiogram before the start of treatment and serial audiometric assessments after treatment. The median audiometric follow-up time was 35.2 months (range, 5.0-89.7 months). Patients underwent a median of 4.5 (range, 1-9) posttreatment audiograms. The ipsilateral cochlea was contoured retrospectively, and dosimetric data were used to determine factors predictive of losing serviceable hearing. The median clinical follow-up time was 29.9 months (range, 1.5-83.6 months). RESULTS: At the time of the last audiometric follow-up, 62% of patients retained serviceable hearing. The actuarial 1-, 2-, and 3-year serviceable hearing preservation rates were 83%, 75%, and 51%, respectively. The estimated median time to loss of serviceable hearing was 42.2 months. On multivariate analysis, cochlear volume <0.15 mL (hazard ratio, 2.849; 95% confidence interval, 1.116-7.270; P = .029) and mean cochlear dose <4000 cGy (hazard ratio, 3.178; 95% confidence interval, 1.116-9.049; P = .030) were statistically significant variables associated with serviceable hearing preservation. The actuarial tumor control was 100%. Three of 39 patients (8%) developed hemifacial spasm after FSRT (House-Brackmann Grade 3), 2 of which completely resolved. No patients experienced deterioration in trigeminal nerve function after FSRT. CONCLUSIONS: Fractionated stereotactic radiation therapy can provide excellent tumor control with acceptable clinical outcomes. The mean dose to the cochlea is highly predictive of the probability of maintaining serviceable hearing after FSRT.