Evaluation of early response to concomitant chemoradiotherapy by interim 18F-FDG PET/CT imaging in patients with locally advanced oesophageal carcinomas.

PURPOSE: The best way to assess the response to chemoradiotherapy of locally advanced oesophageal carcinomas is not known. We used (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT to evaluate the metabolic response during chemoradiotherapy and tried to correlate this response to survival. METHODS: Patients with biopsy-proven oesophageal carcinoma underwent FDG PET/CT with evaluation of the standardized uptake value (SUV) before any treatment (SUV1) and during chemoradiotherapy after two cycles of 5-fluorouracil (FU)/cisplatin and 20 Gy (SUV2). Metabolic response was defined as 1-(SUV2/SUV1). Surgery was discussed after 40 Gy and three cycles of chemotherapy. Results of interim PET were not considered for the therapeutic decision. RESULTS: Among 72 patients who underwent a first FDG PET/CT before any treatment, 59 (82 %) could receive the second FDG PET/CT examination. Median survival was 22.2 months with 1-year and 2-year survivals of 70 and 46 %, respectively. Nineteen patients (32 %) underwent surgery. Mean SUV1 and SUV2 were 12.3 ± 6.2 and 6 ± 4.1, respectively (p < 0.001). Using a cut-off for metabolic response of 50 %, sensitivity and specificity for survival were 0.7 and 0.58. The 2-year overall survival of good responders was 62 % as compared to 27 % for poor metabolic responders. A multivariate analysis was performed, including T and N stages, surgery, histology and metabolic response: only metabolic response was significantly (p = 0.009) associated with 2-year survival. CONCLUSION: Early evaluation of metabolic response had a great prognostic value and could help identify good responders to chemoradiotherapy.

Prognostic significance of anti-p53 and anti-KRas circulating antibodies in esophageal cancer patients treated with chemoradiotherapy.

BACKGROUND: P53 mutations are an adverse prognostic factor in esophageal cancer. P53 and KRas mutations are involved in chemo-radioresistance. Circulating anti-p53 or anti-KRas antibodies are associated with gene mutations. We studied whether anti-p53 or anti-KRas auto-antibodies were prognostic factors for response to chemoradiotherapy (CRT) or survival in esophageal carcinoma. METHODS: Serum p53 and KRas antibodies (abs) were measured using an ELISA method in 97 consecutive patients treated at Saint Louis University Hospital between 1999 and 2002 with CRT for esophageal carcinoma (squamous cell carcinoma (SCCE) 57 patients, adenocarcinoma (ACE) 27 patients). Patient and tumor characteristics, response to treatment and the follow-up status of 84 patients were retrospectively collected. The association between antibodies and patient characteristics was studied. Univariate and multivariate survival analyses were conducted. RESULTS: Twenty-four patients (28%) had anti-p53 abs. Abs were found predominantly in SCCE (p = 0.003). Anti-p53 abs were associated with a shorter overall survival in the univariate analysis (HR 1.8 [1.03-2.9], p = 0.04). In the multivariate analysis, independent prognostic factors for overall and progression-free survival were an objective response to CRT, the CRT strategy (alone or combined with surgery [preoperative]) and anti-p53 abs. None of the long-term survivors had p53 abs. KRas abs were found in 19 patients (23%, no difference according to the histological type). There was no significant association between anti-KRas abs and survival neither in the univariate nor in the multivariate analysis. Neither anti-p53 nor anti-KRas abs were associated with response to CRT. CONCLUSIONS: Anti-p53 abs are an independent prognostic factor for esophageal cancer patients treated with CRT. Individualized therapeutic approaches should be evaluated in this population.

Hypoxia imaging of uterine cervix carcinoma with (18)F-FETNIM PET/CT.

PURPOSE: Our aims were to assess the feasibility of imaging hypoxia in cervical carcinoma with (18)F-fluoroerythronitroimidazole ((18)F-FETNIM) and to compare (18)F-FETNIM uptake with metabolic uptake of (18)F-FDG. PATIENTS AND METHODS: We included 16 patients with cervical carcinoma. After imaging with FDG, (18)F-FETNIM PET/CT was performed and tumor-to-muscle (T/M) ratio uptake was assessed. (18)F- FETNIM uptake was correlated to FDG uptake and osteopontin (OPN), a marker of hypoxia, and patients' outcomes. RESULTS: All tumors were detected by (18)F-FDG PET. (18)F-FETNIM T/M ratios ranged from 1.3 to 5.4. There was no significant correlation between (18)F-FETNIM and (18)F-FDG uptake. High (18)F-FETNIM uptake (T/M > 3.2) was associated with reduced progression-free survival (log-rank = 0.002) and overall survival (log-rank = 0.02). Osteopontin ranged from 39 to 662 µg/L (median, 102.5 µg/L). Patients with OPN greater than 144 µg/L had reduced progression-free survival compared with those with OPN less than 144 µg/L (log-rank = 0.03). We found no significant correlation between (18)F-FETNIM uptake and OPN blood levels. CONCLUSIONS: Our preliminary results showed that a high uptake of (18)F-FETNIM was associated with a worse progression-free and overall survival.

Postoperative chemotherapy followed by conformal concomitant chemoradiotherapy in high-risk gastric cancer.

PURPOSE: To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. METHODS AND MATERIALS: This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36-75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes at 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m²) followed by a bolus of 5-fluorouracil (400 mg/m²) and then a 44-h continuous infusion of 5-fluorouracil (2400-3600 mg/m²) given every 14 days, for three cycles (LV5FU2 protocol). RESULTS: Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. CONCLUSION: Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control.