Systemic Therapy in Advanced Cutaneous Squamous Cell Carcinoma (CSCC): The Roswell Park Experience and a Review of the Literature.

OBJECTIVES: Treatment of locally advanced unresectable or metastatic cutaneous squamous cell carcinoma (mCSCC) is suboptimal with a paucity of robust data on systemic therapy. This retrospective study aimed to evaluate the efficacy and outcomes of patients with locally advanced unresectable or mCSCC treated with systemic therapy. METHODS: Records of patients with CSCC treated with systemic therapy from January 2001 to January 2011 were reviewed. Response was assessed using WHO criteria. Descriptive results were assessed using Wilcoxon rank-sum test for ordinal responses and Pearson χ test for categorical responses. Survival was calculated by the Kaplan-Meier method. RESULTS: Of 28 patients identified, 25 patients (M:F=18:7), median age 66 years (range, 39 to 85 y), had the required data for final analysis. Partial response was 44% and stable disease (SD) was 24%. The median progression-free survival (PFS) and overall survival (OS) were 5.5 months (2.3, 13.2) and 10.9 months (5.3, 21.3) respectively; 3-year OS was 22%. Patients with WHO response had improved PFS (20.8 mo; 4.4, NR) and OS (37.5 mo; 10.3, NR) compared with patients with SD/PD (PFS 2.7 mo; OS 5.9 mo). Use of platinum-based therapy significantly improved PFS and OS, whereas taxanes and cetuximab had no impact in this small cohort. There was no difference in PFS or OS with multiagent versus single-agent therapy. CONCLUSIONS: Platinum-based therapy remains as one of the standard options in advanced CSCC management. Agents to improve response rates are needed and future trials should address the use of novel targeted and new chemotherapy combinations in CSCC.

Neoadjuvant chemoradiotherapy for esophageal/gastroesophageal carcinoma.

BACKGROUND: Esophageal/gastroesophageal junction (GEJ) adenocarcinoma is increasingly treated with trimodality therapy. We present our experience using carboplatin/paclitaxel and radiotherapy followed by surgery. METHODS: Consecutive patients with distal esophageal/GEJ adenocarcinoma (≥T2 or N+) treated from July 2010 to October 2011 were identified. Treatment included neoadjuvant carboplatin/paclitaxel with concurrent radiotherapy (CRT) to 50.4 Gy using an IMRT technique and then Ivor Lewis esophagogastrectomy (ILE). PET/CT was performed prior to and after CRT. Patient/treatment characteristics and tumor response were analyzed. RESULTS: Over this timeframe, 16 patients completed trimodality therapy. All were male, median age of 60 years (45-72 years). All tumors were grade 2-3 with mean tumor length of 4.4 cm (1-9 cm). A median of 6 cycles (5-9 cycles) neoadjuvant carboplatin/paclitaxel were administered. Average time from diagnosis to CRT completion was 76 days (44-141 days) and 60 days (35-92 days) from CRT end to surgery. Neoadjuvant CRT was well tolerated with mean weight loss of 3.9 kg. All pts had R0 resections. No anastomotic leaks or perioperative mortality occurred. Mean hospital stay was 13 days (8-28 days). Pathologic complete response (pCR) was seen in 38% of patients, microscopic residual disease (isolated tumor cells or <2 mm) in 31%, and macroscopic residual disease remained in 31%. Mean SUV reduction was 41% (0-100%). Of 11 patients with ≥35% SUV decrease, 45% had pCR and 27% had microscopic residual disease. Three patients had signet ring features. Of these, 2 had no SUV reduction and all had gross residual disease, including the only patient with positive nodal disease. CONCLUSIONS: Trimodality therapy utilizing concurrent carboplatin/paclitaxel and radiotherapy to 50.4 Gy followed by surgery was well tolerated and resulted in significant pathologic complete response or minimal residual disease. Further investigation of predictive factors for response is needed to best tailor therapy in the management of esophageal/GEJ adenocarcinoma.

The role of radiation in the perioperative treatment of esophagogastric cancer.

Cancers of the esophagus, stomach, and the esophagogastric junction (EGJ) remain a global health problem. There has been a dramatic increase in the incidence of adenocarcinoma of the distal esophagus and EGJ in the past two decades with little change in the poor prognosis associated with these cancers. Previously surgery alone was the mainstay of therapeutic intervention, but high rates of local and systemic failure have prompted investigation into neoadjuvant and adjuvant therapy. Treatment paradigms differ across continents, but the unifying theme that has emerged in the past decade implies that surgery alone can no longer be considered the standard of care. The multi-disciplinary management of patients with locally advanced esophagogastric carcinomas using trimodality therapy with radiotherapy, chemotherapy, and surgery confers the greatest opportunity for margin negative resection, improved loco-regional control and cure, and should be the accepted treatment paradigm. The traditional backbone of platinum plus fluorouracil concurrent with radiotherapy may be supplanted by more modern, easier-to-administer regimens incorporating taxanes and irinotecan. The current generation of clinical trials in this heterogeneous group of diseases is examining targeted therapy, newer methods of radiotherapy, and predictors of response to therapy aiming to tailor management to an individual patient.