Marc A. Shapiro

Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline

PURPOSE To provide evidence-based recommendations to oncologists and others on potentially curative therapy for patients with localized pancreatic cancer. METHODS ASCO convened a panel of medical oncology, radiation oncology, surgical oncology, palliative care, and advocacy experts and conducted a systematic review of literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events. RESULTS Nine randomized controlled trials met the systematic review criteria. RECOMMENDATIONS A multiphase computed tomography scan of the abdomen and pelvis or magnetic resonance imaging should be performed for all patients to assess the anatomic relationships of the primary tumor and for the presence of intra-abdominal metastases. Baseline performance status, comorbidity profile, and goals of care should be evaluated and established. Primary surgical resection is recommended for all patients who have no metastases, appropriate performance and comorbidity profiles, and no radiographic interface between primary tumor and mesenteric vasculature. Preoperative therapy is recommended for patients who meet specific characteristics. All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of contraindications. Adjuvant chemoradiation may be offered to patients who did not receive preoperative therapy with microscopically positive margins (R1) after resection and/or who had node-positive disease after completion of 4 to 6 months of systemic adjuvant chemotherapy. Patients should have a full assessment of symptoms, psychological status, and social supports and should receive palliative care early. Patients who have completed treatment and have no evidence of disease should be monitored. Additional information is available at www.asco.org/guidelines/PCPC and www.asco.org/guidelineswiki.

Predicting early mortality in resectable pancreatic adenocarcinoma: A cohort study

Survival after surgical resection for pancreatic cancer remains poor. A subgroup of patients die early (<6 months), and understanding factors associated with early mortality may help to identify high‐risk patients. The Khorana score has been shown to be associated with early mortality for patients with solid tumors. In the current study, the authors evaluated the role of this score and other prognostic variables in this setting.

Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update

Purpose To update the Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline published on May 31, 2016. The October 2016 update focuses solely on new evidence that pertains to clinical question 4 of the guideline: What is the appropriate adjuvant regimen for patients with pancreatic cancer who have undergone an R0 or R1 resection of their primary tumor? Methods The recently published results of a randomized phase III study prompted an update of this guideline. The high quality of the reported evidence and the potential for its clinical impact prompted the Expert Panel to revise one of the guideline recommendations. Results The ESPAC-4 study, a multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy compared gemcitabine and capecitabine with gemcitabine monotherapy in 730 evaluable patients with resected pancreatic ductal adenocarcinoma. Median overall survival was improved in the doublet arm to 28.0 months (95% CI, 23.5 to 31.5 months) versus 25.5 months (95% CI, 22.7 to 27.9 months) for gemcitabine alone (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = .032). Grade 3 and 4 adverse events were similar in both arms, although higher rates of hand-foot syndrome and diarrhea occurred in patients randomly assigned to the doublet arm. Recommendations All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of medical or surgical contraindications. The doublet regimen of gemcitabine and capecitabine is preferred in the absence of concerns for toxicity or tolerance; alternatively, monotherapy with gemcitabine or fluorouracil plus folinic acid can be offered. Adjuvant treatment should be initiated within 8 weeks of surgical resection, assuming complete recovery. The remaining recommendations from the original 2016 ASCO guideline are unchanged.

Stereotactic body radiation therapy-based treatment model for stage I medically inoperable small cell lung cancer

PURPOSE To report on medically inoperable stage I small cell lung cancer (SCLC) patients for whom stereotactic body radiation therapy (SBRT) was employed to manage the primary tumor. METHODS AND MATERIALS Review of our institutional review board approved SBRT registry revealed 6 cases of stage I SCLC out of 430 patients over a 6-year interval (2004-2010). All patients had biopsy proven disease and deemed medically inoperable by a thoracic surgeon. Our institutional approach was to treat with a combination of SBRT, platinum-etoposide chemotherapy (CHT) and prophylactic cranial irradiation (PCI). SBRT was delivered using a Novalis/BrainLAB platform and ExacTrac (BrainLab, Westchester, IL) for image guidance. RESULTS Patient characteristics included a median Karnofsky performance scale of 80, a median age of 68 years, 4 females, and 1 patient still smoking at presentation. Impaired pulmonary function caused inoperability in 50% of cases. Tumor characteristics included median tumor size of 2.6 cm and median positron emission tomography-standard uptake valuemax of 9. The SBRT was 60 Gy/3 fractions (3 patients), 50 Gy/5 fractions (2 patients), 30 Gy/1 fraction (1 patient). Median follow-up was 11.9 months. There was no grade 3 or higher, and 1 grade 2, toxicity. Three patients were alive at analysis and 3 patients had died of non-cancer causes. At 1 year, local control was 100%, there was no regional nodal failure, and 1 patient had distant failure (liver). Overall and disease-free survivals at 1 year were 63% and 75%, respectively. CONCLUSIONS Employing SBRT for stage I medically inoperable SCLC is rational, with excellent local control and encouraging disease-specific survival. The absence of regional nodal failure supports positron emission tomography for mediastinal staging. Platinum-based CHT may be feasible in vulnerable populations.

Patient-centered outcomes with post-approval nivolumab in metastatic NSCLC at the Cleveland Clinic Taussig Cancer Institute (TCI).

29 Background: Patient-centered outcomes are important quality metrics of value-based cancer care. For NSCLC, these include chemotherapy administration within 30 days of death and end of life hospitalizations. Nivolumab was initially FDA approved in March 2015 for second-line therapy of squamous NSCLC and subsequently for non-squamous NSCLC. To evaluate the impact of post-approval nivolumab use on patient-centered outcomes, a retrospective review was performed of patients (pts) with metastatic NSLCC receiving nivolumab at TCI main campus and regional centers. METHODS All pts with NSCLC receiving nivolumab from 3/4/15 to 10/5/15 were identified (cohort A) and treatment characteristics were collected from pharmacy, billing, and tumor registry databases and manual chart review. Similar data for a cohort of NSCLC pts (cohort B) initiating care with 4 academic thoracic and 12 community TCI oncologists from 1/1/12 to 7/1/13 and who received second-line therapy were used for comparison. RESULTS 113 cohort A pts received nivolumab with a median follow up of 101 days. 82 (73%) were alive at the time of evaluation. 70 (62%) received ≤ 1 prior chemotherapy regimens for metastatic disease. 19 of 52 (37%) cohort A pts completing nivolumab received drug within 30 days of death, 13 (68%) of whom had received ≤ 1 prior chemotherapy regimens. 3 of 50 (6%) cohort B pts completing second-line therapy received drug within 30 days of death. In patients with a known date of death, median time from first dose of nivolumab in cohort A and second-line therapy in cohort B and death was 41 and 145 days respectively. 28 (25%) cohort A pts and 18 (36%) cohort B pts were hospitalized at a TCI facility during therapy. CONCLUSIONS This study shows the brisk uptake of nivolumab to clinical practice, but with potential for inappropriate utilization. Continued evaluation of practice patterns is necessary including cost analysis. Further research is needed to better understand outcomes in patients with EGOG PS ≥ 2, front-line use, and cost effectiveness.

Data collection for care pathways in the Cleveland Clinic Health System.

115 Background: Care pathways are established methods of reducing healthcare costs and disparities in oncology care. To demonstrate their impact, health systems must measure and report data on care pathway adherence and outcomes in near real-time. Automating data abstraction across a health system for oncology is difficult due to the amount and detail of data required. Manual abstraction of data is considered slow and costly. Many consider Electronic Medical Record (EMR) integration of care pathways essential in order to successfully implement and assess. METHODS 7 medical oncology care pathways and 45 medical oncologists across the health system were selected for a pilot study to assess the feasibility of implementing care pathways throughout the enterprise. The pilot study also allowed for testing of data collection capabilities. Patients eligible for the care pathways were prospectively identified by manual review of physician calendars. A small number of data points were manually abstracted from the patient EMR at the time of identification. Endpoints of interest, such as hospitalization rates, chemotherapy administered, time to treatment, and costs of care were reconciled through pre-existing databases within pharmacy, research, and finance. Tumor registry data identified a retrospective cohort. RESULTS Over 1,000 patients were prospectively identified for the care pathway pilot between 1/1/2014 and 12/31/2014. The tumor registry identified 700 additional retrospective patients. The rapid analyses possible as a result of these efforts demonstrated physician adherence, improved patient outcomes, and significant cost savings. In one example, a care pathway for metastatic non-small cell lung cancer reduced charges by more than

Novel pharmacologic approach to enhance the epigenetic and immune priming effect of decitabine in patients with advanced non-small cell lung cancer

98,000/patient by recommending patients receive one standardized chemotherapeutic regimen. CONCLUSIONS Timely data collection for oncology care pathways is feasible and cost effective without EMR integration. Manual identification of patients combined with pre-existing data sources allowed for near-real time analysis of care pathways and provided valuable information about care pathway impact. Institutions can implement and assess care pathways with resources already available to them.

SELECT: A multicenter phase II trial of adjuvant erlotinib in resected early-stage EGFR mutation-positive NSCLC.

Meeting abstracts DNA methyl transferase 1 (DNMT-1) is a key epigenetic enzyme in cancer cells which inactivates proliferation terminating genes and downregulates the expression of cancer related proteins and neoantigens by hypermethylation. Prolonged exposure of tumor cells to DAC is required for