A comparison of carboplatin and paclitaxel with cisplatinum and 5-fluorouracil in definitive chemoradiation in esophageal cancer patients.

BACKGROUND: In esophageal cancer (EC) patients who are not eligible for surgery, definitive chemoradiation (dCRT) with curative intent using cisplatinum with 5-fluorouracil (5-FU) is the standard chemotherapy regimen. Nowadays carboplatin/paclitaxel is also often used. In this study, we compared survival and toxicity rates between both regimens. PATIENTS AND METHODS: This multicenter study included 102 patients treated in five centers in the Northeast Netherlands from 1996 till 2008. Forty-seven patients received cisplatinum/5-FU (75 mg/m(2) and 1 g/m(2)) and 55 patients carboplatin/paclitaxel (AUC2 and 50 mg/m(2)). RESULTS: Overall survival (OS) was not different between the cisplatinum/5-FU and carboplatin/paclitaxel group {[P = 0.879, hazard ratio (HR) 0.97 [confidence interval (CI) 0.62-1.51]}, with a median survival of 16.1 (CI 11.8-20.5) and 13.8 months (CI 10.8-16.9). Median disease-free survival (DFS) was comparable [P = 0.760, HR 0.93 (CI 0.60-1.45)] between the cisplatinum/5-FU group [11.1 months (CI 6.9-15.3)] and the carboplatin/paclitaxel group [9.7 months (CI 5.1-14.4)]. Groups were comparable except clinical T stage was higher in the carboplatin/paclitaxel group (P = 0.008). High clinical T stage (cT4) was not related to OS and DFS in a univariate analysis (P = 0.250 and P = 0.201). A higher percentage of patients completed the carboplatin/paclitaxel regimen (82% versus 57%, P = 0.010). Hematological and nonhematological toxicity (≥grade 3) in the carboplatin/paclitaxel group (4% and 18%) was significantly lower than in the cisplatinum/5-FU (19% and 38%, P = 0.001). CONCLUSIONS: In this study, we showed comparable outcome, in terms of DFS and OS for carboplatin/paclitaxel compared with cisplatinum/5-FU as dCRT treatment in EC patients. Toxicity rates were lower in the carboplatin/paclitaxel group together with higher treatment compliance. Carboplatin/paclitaxel as an alternative treatment of cisplatinum/5-FU is a good candidate regimen for further evaluation.

Impact of 18-fluorodeoxyglucose positron emission tomography on computed tomography defined target volumes in radiation treatment planning of esophageal cancer: reduction in geographic misses with equal inter-observer variability: PET/CT improves esophageal target definition.

Target volume definition in modern radiotherapy is based on planning computed tomography (CT). So far, 18-fluorodeoxyglucose positron emission tomography (FDG-PET) has not been included in planning modality in volume definition of esophageal cancer. This study evaluates fusion of FDG-PET and CT in patients with esophageal cancer in terms of geographic misses and inter-observer variability in volume definition. In 28 esophageal cancer patients, gross, clinical and planning tumor volumes (GTV; CTV; PTV) were defined on planning CT by three radiation oncologists. After software-based emission tomography and computed tomography (PET/CT) fusion, tumor delineations were redefined by the same radiation-oncologists. Concordance indexes (CCI's) for CT and PET/CT based GTV, CTV and PTV were calculated for each pair of observers. Incorporation of PET/CT modified tumor delineation in 17/28 subjects (61%) in cranial and/or caudal direction. Mean concordance indexes for CT-based CTV and PTV were 72 (55-86)% and 77 (61-88)%, respectively, vs. 72 (47-99)% and 76 (54-87)% for PET/CT-based CTV and PTV. Paired analyses showed no significant difference in CCI between CT and PET/CT. Combining FDG-PET and CT may improve target volume definition with less geographic misses, but without significant effects on inter-observer variability in esophageal cancer.

Radiation-induced apoptosis in relation to acute impairment of rat salivary gland function.

PURPOSE: To find an answer to the question: Are the acute radiation effects on salivary gland function, as seen in earlier studies, causally related to radiation-induced apoptosis? MATERIALS AND METHODS: Rat parotid and submandibular glands were X-irradiated with doses up to 25 Gy and morphological damage assayed up to 6 days after irradiation. Damage to the different cell types in the glands was assessed after H & E staining. Apoptotic appearance was judged by compacted chromatin and fragmentation of cells into lobulated masses. RESULTS: In about 3% of the cells aberrant nuclei were observed after doses as low as 2 Gy and around 7.5 and 24 h after irradiation. About half of these aberrant nuclei had an apoptotic appearance. After a dose of about 5 Gy no dose-response for apoptotic cells was found, as evidenced by a plateau in the dose-effect curve. At 6 days after 2 Gy, no signs of radiation-induced apoptosis was apparent and for most cell types a value close to zero was observed. CONCLUSIONS: Radiation studies on salivary function in the rat show the typical response with respect to dose (5-15 Gy) and time (1-3 days). This differs from reported findings with light microscopy. Therefore, the extent of apoptosis induced by radiation cannot explain the observed gland malfunction. Alternative mechanisms are proposed.