A. Ruol

Surgical and endoscopic palliation of esophageal carcinoma

We reviewed the records of 732 patients with advanced esophageal carcinoma to determine the efficacy of palliative therapy. Palliative resection was performed in 156 patients. Hospital mortality was 9.6%, 1-year survival was 29.1%, and median survival was 7.8 months. Excellent or good palliative results were obtained in 78% of operative survivors. Bypass procedures were performed in 49 patients: hospital mortality was 20.4%, with a median survival of 6.2 months. Excellent or good palliative results were obtained in 71% of operative survivors. Intubation of the tumor was performed in 254 patients. Thirty-day mortality was 10.2%, and median survival was 4.0 months. No patient received excellent palliation. Neodymium:yttrium-aluminum-garnet laser therapy or photodynamic therapy was performed in 50 patients. No procedure-related deaths were recorded, and median survival was 4.1 months. Excellent or good results were obtained in 83% of patients. Lesser procedures were performed in 106 patients, and 117 had only staging examinations. Although surgical palliation of esophageal cancer with resection or bypass provides good results, the cost is high. Improvements in palliative results require reduction in operative mortality, increased accuracy of preoperative staging, continuing use of laser therapy, and increased use of chemotherapy alone or in combination with radiotherapy and operation.

A multicenter phase II study of induction chemotherapy with FOLFOX-4 and cetuximab followed by radiation and cetuximab in locally advanced oesophageal cancer.

Background:Preoperative chemoradiotherapy (CRT) improves the survival of patients with oesophageal cancer when compared with surgery alone.Methods:We conducted a phase II, multicenter trial of FOLFOX-4 and cetuximab in patients with locally advanced oesophageal cancer (LAEC) followed by daily radiotherapy (180u2009cGy fractions to 5040u2009cGy) with concurrent weekly cetuximab. Cytokines levels potentially related to cetuximab efficacy were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, at week 8 and at week 17. Primary end point was complete pathological response rate (pCR).Results:In all, 41 patients were enroled. Among 30 patients who underwent surgery, a pCR was observed in 8 patients corresponding to a rate of 27%. The most frequent grade 3/4 toxicity was skin (30%) and neutropenia (30%). The 36-month survival rates were 85 and 52% in patients with pathological CR or PR vs 38 and 33% in patients with SD or PD.Conclusions:Incorporating cetuximab into a preoperative regimen for LAEC is feasible; no correlation between cytokines changes and patient outcome was observed. Positron emission tomography/computed tomography study even if influenced by the small number of patients appears to be able to predict patients outcome both as early and late metabolic response.

Correlation between automated karyometric measurements of squamous cell carcinoma of the esophagus and histopathologic and clinical features

The clinical staging of esophageal carcinoma is unreliable currently, making it difficult to select patients for aggressive therapy. To further refine staging criteria, the nuclear characteristics of a series of 31 patients with squamous cell carcinoma of the esophagus were studied using a computerized image analysis system (MicroTICAS). Karyometric measurements, including total nuclear DNA content, nuclear area, and nuclear roundness were compared with various clinical and histologic variables. Nearly all tumors (30 of 31) were aneuploid. Tumors with nuclear areas greater than 70 μm2 were associated with transmural esophageal penetration (P < 0.05) and to a lesser extent with poor survival (less than 6 months; P = 0.06). Surprisingly, nuclear ploidy did not correlate with either variable. These data support a role for nuclear analysis on preoperative biopsy specimens as an adjunct in clinical staging.

6566 A multicenter phase II study of induction CT with Folfox-4 and Cetuximab followed by RT and Cetuximab in locally advanced esophageal cancer (LAEC)

4546 Background: Preoperative CRT improves the survival of pts with EC when compared with surgery alone. Epidermal growth factor receptor (EGFR) is overexpressed in 30-90% of EC and is associated with poor prognosis, providing the rationale for using the anti-EGFR monoclonal antibody cetuximab (C). The purpose of the study was to investigate the efficacy, toxicity and feasibility of C with FOLFOX- 4 regimen as induction CT followed by C and RT in pts with LAEC in a multicenter setting.nnnMETHODSnEligibility criteria: resectable, locally advanced (uT3 or uN1, T4 if deemed resectable) squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the esophagus; staged by EUS, CT and PET scan; age 18-70y; PS <2; normal organ functions.All pts received induction treatment with C at a starting dose of 400 mg/m2 and further weekly infusion at a maintenance dose of 250 mg/m2 and 4 cycles of FOLFOX-4 every two weeks. Post-induction EUS and CT scans were performed, while a PET scan was repeated early before second cycle of CT: pts without PD were given daily RT (180cGy fractions to 5040cGy) with concurrent weekly C. Post RT, EUS plus biopsies, CT scan and PET were performed. At wk 18, pts without PD had esophagectomy. Simons two stage design was used. Primary endpoint was histopathological response rate.nnnRESULTSnUp to December 2008, 40 pts, 30 men, were enrolled from 4 institutions; median age 59 y (35-70y); AC 12; SCC 28; stage II 15, stage III 25 pts. At this time 32/40 pts were evaluable. The most frequent grade 3/4 toxicity of chemoradiotherapy were skin (32%),neutropenia (29%) and esophagitis (9%); 10 pts had no resection (9 progressive disease,1 patients refusal). Of 22 operated pts, 17 pts (77%) had RO-resection, 5 pts had palliative surgery.2 pts died due to complications after surgery (1 after > 30 days). The pathological response rate was 68 %, with a complete histopathological remission recorded in 6 pts (27%);17 pts (53%) are still alive without residual or recurrent disease.nnnCONCLUSIONSnThe current findings suggest the feasibility of incorporating cetuximab into a preoperative regimen for LAEC pts and an encouraging antineoplastic activity with 68% histopathological responders. No significant financial relationships to disclose.