Kim Anna Reiss

Starting Dose of Sorafenib for the Treatment of Hepatocellular Carcinoma: A Retrospective, Multi-Institutional Study

Purpose Sorafenib is currently the only Food and Drug Administration-approved first-line therapy for patients with advanced hepatocellular carcinoma. There are few data examining how sorafenib starting dose may influence patient outcomes and costs. Patients and Methods We retrospectively evaluated 4,903 patients from 128 Veterans Health Administration hospitals who were prescribed sorafenib for hepatocellular carcinoma between January 2006 and April 2015. After 1:1 propensity score matching to account for potential treatment bias, hazard ratios (HRs) were calculated using Cox regression and were tested against a noninferiority margin of HR = 1.1. A matched multivariate logistic regression was performed to adjust for potential confounders. The primary end point was overall survival (OS) of patients who were prescribed standard starting dosage sorafenib (800 mg/d per os) versus that of patients who were prescribed reduced starting dose sorafenib (< 800 mg/d per os). Results There were 3,094 standard dose sorafenib patients (63%) and 1,809 reduced starting dose sorafenib patients (37%). Reduced starting dose sorafenib patients had more Barcelona Clinic Liver Cancer stage D ( P < .001), higher Model for End-Stage Liver Disease Sodium scores ( P < .001), higher Child-Turcotte-Pugh scores ( P < .001), and higher Cirrhosis Comorbidity Index scores ( P = .01). Consequently, reduced starting dose sorafenib patients had lower OS (median, 200 v 233 days, HR = 1.10). After propensity score matching and adjusting for potential confounders, there was no longer a significant OS difference (adjusted hazard ratio [HRadj], 0.92; 95% CI, 0.83 to 1.01), and this fell significantly below the noninferiority margin ( P < .001). Reduced starting dose sorafenib patients experienced significantly lower total cumulative sorafenib cost and were less likely to discontinue sorafenib because of gastrointestinal adverse effects (8.7% v 10.8%; P = .047). Conclusion The initiation of sorafenib therapy at reduced dosages was associated with reduced pill burden, reduced treatment costs, and a trend toward a decreased rate of discontinuing sorafenib because of adverse events. Reduced dosing was not associated with inferior OS relative to standard dosing.

Retrospective Survival Analysis of Patients With Advanced Pancreatic Ductal Adenocarcinoma and Germline BRCA or PALB2 Mutations

PURPOSEGermline mutations in the homologous recombination genes BRCA1, BRCA2, and PALB2 confer an increased risk for pancreatic ductal adenocarcinoma (PDAC). Tumors associated with mutations in hom...

Growing Pains: a Simulation-Based Curriculum for Improving the Transition to Hematology/Oncology Fellowship

Trainee exposure to clinical oncology during residency training is heterogeneous and often modest. The steep learning curve upon entry into fellowship can result in undue stress for fellows and their patients. Simulation-based training has been shown to be superior to classical didactic approaches. We have introduced several innovative simulation-based workshops into the curriculum for the Johns Hopkins Hematology/Oncology Fellowship Training Program in order to address this unmet need. During the first months of training, fellows were engaged in activities emphasizing essential clinical and procedural skills. Specific workshops included the following: (1) chemotherapy writing, (2) cadaveric and simulation-based bone marrow biopsy and intrathecal chemotherapy administration, and (3) simulation-based communication skills training. All first-year fellows in our program participated in these exercises. Pre- and post-workshop surveys were administered to assess knowledge, attitudes, and behaviors; additional distant post-workshop evaluations were disseminated to assess the durability/impact of the curricula and for program evaluation. Overall, participating fellows indicated that the workshops improved patient care and comfort with procedures and patient-centered communication. Continued implementation of these workshops was recommended for program improvement. To the best of our knowledge, ours is amongst the first oncology fellowship training programs to systematically implement simulation-based curricula into our schema for fellowship training. We hypothesize that proactively introducing fellows to these high-yield activities will translate into improved patient care and reduced stress for trainees. Additional investigation into the long-term impact of such curricula remains an area of ongoing need.

Comparative Effectiveness of Neoadjuvant Chemoradiation Versus Upfront Surgery in the Management of Recto-Sigmoid Junction Cancer

Micro‐Abstract: The optimal management of patients with locally advanced recto‐sigmoid cancer is unclear. Using the National Cancer Database, we assessed patterns of care and outcomes associated with upfront surgery versus neoadjuvant chemoradiation followed by surgery. Although neoadjuvant chemoradiation was used in a small percentage of patients, its use was associated with more complete resections, a robust pathologic complete response rate, and improved overall survival. Introduction: The optimal management of locally advanced recto‐sigmoid cancer is unclear. Although some experts advocate for upfront surgery, others recommend neoadjuvant chemoradiation followed by surgery. We used the National Cancer Database to characterize patterns‐of‐care and overall survival (OS) associated with these treatment strategies. Patients and Methods: Patients with clinical stage II or III recto‐sigmoid cancer who underwent surgery with or without adjunctive chemotherapy and/or radiotherapy from 2006 to 2014 were identified, and dichotomized into: (1) upfront surgery, and (2) neoadjuvant chemoradiation cohorts. Patterns‐of‐care were assessed using multivariable logistic regression. The association between neoadjuvant chemoradiation use and OS was assessed using Cox proportional hazards analysis with propensity score‐matching. Results: Of 9313 identified patients, 6756 (73%) underwent upfront surgery and 2557 (27%) received neoadjuvant chemoradiation. Treatment at academic facilities and higher clinical T stage were predictors of neoadjuvant chemoradiation use. Compared with upfront surgery, neoadjuvant chemoradiation resulted in fewer positive circumferential resection margins (384 [11%] patients vs. 108 [8%] patients; P = .001), and 478 [18.7%] patients achieved a pathologic complete response at surgery. In propensity score‐matched analysis, neoadjuvant chemoradiation use was associated with improved OS (hazard ratio, 0.79; 95% confidence interval, 0.69–0.90) compared with upfront surgery; 5‐year estimated OS was 77.0% versus 72.0%, respectively. The improvement in OS persisted in landmark analysis of patients who survived at least 12 months. Conclusion: Only a small percentage of patients with locally advanced recto‐sigmoid cancer receive neoadjuvant chemoradiation even though its use might result in improved OS relative to upfront surgery. Prospective research is warranted to validate and standardize therapeutic strategies in patients with recto‐sigmoid cancer.

Immune Control Despite Protracted Lymphopenia After Chemoradiation in an Elite Controller

Elite controllers are human immunodeficiency virus-1–positive individuals capable of sustaining undetectable viral loads without treatment. We present the case of an elite controller diagnosed with extensive stage small cell lung cancer who maintained a viral load of <20 copies/mL despite the development of severe treatment-related lymphopenia.