Preoperative chemoradiation for rectal cancer using capecitabine and celecoxib correlated with posttreatment assessment of thymidylate synthase and thymidine phosphorylase expression.

PURPOSE: Thymidylate synthase (TS) and thymidine phosphorylase (TP) expression have been shown to be predictors of response to therapy. The toxicity, efficacy, surgical morbidity, and immunohistochemical TS and TP expression were assessed in surgical resection specimens after preoperative chemoradiation. METHODS AND MATERIALS: Twenty patients with clinical stage I to III rectal adenocarcinoma received preoperative chemoradiation and underwent surgical resection 6 weeks later. RESULTS: Posttreatment tumor stages were T1 to T2 and N0 in 30% of patients; T3 to T4 and N0 in 30% of patients; and T1 to T3 and N1 to N2 in 15% of patients. Pathologic complete response (pCR) was evident in 25% and tumor regression occurred in a total of 80% of patients. Anal sphincter-sparing surgery was performed in 80% of cases. Acute and perioperative complications were minimal, with no grade 3/4 toxicity or treatment breaks. Pelvic control was obtained in 90% of patients. With a median follow-up of 65.5 months (range, 8-80 months), the 6-year actuarial survival rate was 75%. Local failure was significantly associated with nonresponse to therapy and with high TS and low TP expression (p = 0.008 and p = 0.04, respectively). CONCLUSIONS: The combination of capecitabine, celecoxib, and x-radiation therapy yields excellent response: a 25% pathologic pCR, no acute grade 3/4 toxicity, and minimal surgical morbidity. Nonresponders expressed significantly increased TS levels and decreased TP levels in posttreatment resection specimens compared to responders.

Dose as a function of lung volume and planned treatment volume in helical tomotherapy intensity-modulated radiation therapy-based stereotactic body radiation therapy for small lung tumors.

PURPOSE: To evaluate the limitations of Hi-Art Helical Tomotherapy (Middleton, WI) stereotactic body radiotherapy (SBRT) for lung lesions, and to provide an initial report on patients treated with this method. Stereotactic body radiotherapy was shown to be an effective, well-tolerated treatment for early-stage, non-small-cell lung carcinoma (NSCLC). The Radiation Therapy Oncology Group (RTOG) 0236 protocol is currently evaluating three-dimensional conformal SBRT that delivers 60 Gy in three fractions. METHODS AND MATERIALS: Inverse treatment planning for hypothetical lung gross tumor volumes (GTV) and planned treatment volume (PTV) expansions were performed. We tested the hypothesis that the maximum acceptable dose (MAD) to be delivered to the lesion by SBRT could be predicted by PTV and lung volume. Dose constraints on normal tissue were as designated by the RTOG protocol. Inverse planning was performed to find the maximum tolerated SBRT dose up to 60 Gy. RESULTS: Regression analysis of the data obtained indicated a linear relationship between MAD, PTV, and lung volume. This generated two equations which may be useful predictive tools. Seven patients with Stage I and II NSCLC treated at the University of Virginia with this method tolerated the treatment extremely well, and suffered no greater than grade I toxicity, with no evidence of disease recurrence in follow-up from 2-20 months. CONCLUSIONS: Helical tomotherapy SBRT for lung lesions is well-tolerated. In addition, the likely MAD for patients considered for this type of treatment can be predicted by PTV and lung volume.