Increased expression of VEGF and CD31 in postradiation rectal tissue: implications for radiation proctitis.

Background. Inflammation mediators related to radiation proctitis are partially elucidated, and neovascularization is thought to play a key role. Objectives. To investigate the expression of vascular endothelial growth factor (VEGF) and CD31 as angiogenetic markers in postradiation rectal tissue. Methods. Rectal mucosa biopsies from 11 patients who underwent irradiation for prostate cancer were examined immunohistochemically for the expression of VEGF and CD31 at three time settings-before, at the completion of, and 6 months after radiotherapy. VEGF expressing vascular endothelial cells and CD31 expressing microvessels were counted separately in 10 high-power fields (HPFs). VEGF vascular index (VEGF-VI) and microvascular density (MVD) were calculated as the mean number of VEGF positive cells per vessel or the mean number of vessels per HPF, respectively. Histological features were also evaluated. Results. VEGF-VI was significantly higher at the completion of radiotherapy (0.17 ± 0.15 versus 0.41 ± 0.24, P = 0.001) declining 6 months after. MVD increased significantly only 6 months after radiotherapy (7.3 ± 3.2 versus 10.5 ± 3.1, P < 0.005). The histopathological examination revealed inflammatory changes at the completion of radiotherapy regressing in the majority of cases 6 months after. Conclusions. Our results showed that in postradiation rectal biopsy specimens neoangiogenesis seems to be inflammation-related and constitutes a significant postradiation component of the tissue injury.

A pilot study on concurrent platinum chemotherapy and intracavitary brachytherapy for locally advanced cancer of the uterine cervix.

This study aims to evaluate the feasibility, toxicity and efficacy of concurrent chemotherapy with platinum compounds and brachytherapy, for locally advanced carcinoma of the cervix (Stages IIA/B, IIIA). The hypothesis was that synchronous chemo-brachytherapy may be sufficient to cause down-staging of the tumour, to render it operable, and hopefully improve the prognosis. 36 women with locally advanced cervical cancer were treated with concomitant brachytherapy and chemotherapy before surgery and/or definitive external radiotherapy. All patients received two caesium-137 Selectron MDR applications, 1 week apart. The dose calculated to point A for each implant was 20-25 Gy. Chemotherapy consisting of continuous cisplatin infusion (50 mg m2) and of carboplatin (300 mg m-2) was given simultaneously with intracavitary irradiation during the first and second application, respectively. The combined therapy was followed when feasible by radical hysterectomy, pelvic lymphadenectomy and pelvic radiotherapy. Patients deemed ineligible for surgery because of poor response were given full dose external radiotherapy. 31/36 patients were treated by Wertheim hysterectomy of whom 10 had negative lymph nodes and resection margins. Definitive external radiotherapy was given in the remaining five patients. Overall, 83% were disease free at 2.8 years mean follow-up. The most frequent acute side-effects of chemobrachytherapy were nausea and vomiting. No renal toxicity was observed. Thrombocytopenia was seen in five patients and was responsible for delayed surgery in four patients. Concerning late effects, two patients developed grade 2 intestinal sequelae, two mild frequency and two vaginal stenosis. One rectovaginal and one vesicovaginal fistula developed in two patients; and a third patient had a fistula associated with tumour recurrence. Concurrent brachytherapy and chemotherapy with platinum compounds is well tolerated and effective in reducing tumour bulk before definitive local treatment (surgery or external radiotherapy), in patients with locally advanced carcinoma of the uterine cervix.

Concurrent platinum and docetaxel chemotherapy and external radical radiotherapy in patients with invasive transitional cell bladder carcinoma. A preliminary report of tolerance and local control.

PURPOSE: The present study aims to evaluate the feasibility, toxicity, and efficacy of concurrent chemotherapy with cisplatinum and docetaxel, and external radical radiotherapy for transitional cell carcinoma of urinary bladder. MATERIALS AND METHODS: 42 patients (34 men, 8 females) with invasive bladder carcinoma (clinical stages T1-4) were treated after transurethral biopsy with chemotherapy and concomitant external radiotherapy. Chemotherapy consisting of cisplatin infusion (30 mg/m2) and Docetaxel (40 mg/m2) was given twice a week simultaneously with-irradiation during the whole treatment period (6-8 weeks) as follows: Cisplatin (D1,D8,D15,D22, D25,D36,D43,D50) and Docetaxel (D4, D11, D18, D25, D32, D39, D46, D53). An external irradiation scheme 1.8 to 2.0 Gy per fraction, 5 days a week was used up to 68-74 Gy (6MeV photons) total tumor dose. RESULTS: All but S patients completed the planned chemoradiation protocol. The complete response rate (CR-rate) assessed at 3 months after completion of combined treatment was 100%, 63.6%, 46.15% and 95% for clinical stage (c) cT1 (9/9), cT2 (7/11), cT3 (6/13) and cT4 (1/4) cases respectively. None of 9 patients with T1 tumors had any local failure at 36.1 months mean follow-up time. In total, 9 of 37 patients (24.32%) relapsed locally and/or distantly and were followed for 25.04 months (mean time), 50% of the relapses occurred at a mean time of 7.25 months. The mortality rate was 10.81% (4/37). All these patients died with a mean time of 11 months. 32 cases remain alive 19-46 months after treatment; 27 of those are with no evidence of disease with a mean follow-up time of 32.24 months. In total, there was a 78.50% (30/37) and a 75.67%, (28/37) rate of overall survival and pelvic control respectively at 25.04 months mean follow-up time. Chemotherapy was discontinued in 2 cases due to acute gastrointestinal toxicity and in 3 more, due to patient compliance. There was 1 toxic death 2 months after treatment completion due to ureteral obstruction and impaired renal function. The acute toxicity was estimated as moderate to severe and caused the interruption of treatment for 5 to 10 days in 8 of 37 patients (21.62%). Myelotoxicity appeared in 22/37 patients but febrile grade III and IV neutropenia was observed in 3 patients (8.10%) and thrombocytopenia (Grade I-III) in 8 (21.62%). Concerning late effects a sigmoid stricture, a transient small bowel obstruction, 4 patients with contracted bladder and 1 case with renal failure were found. Grade I to III hypersensitivity reactions appeared in 8/37 patients (21.62%) while stomatitis (grade I-II) and grade II skin toxicity appeared in 3 and 4 patients respectively. These and other symptoms (Grade I to II peripheral edema, transient myalgias and arthralgias in 7/37 cases), paresthesias or numbness (3/37) and peripheral motor dysfunction (1/37) were responsible for early reduction of docetaxel dose from 40 mg/m2 to 20 mg/m2. CONCLUSION: This preliminary analysis suggest that the radiosensitizing effect of cisplatin and docetaxel to megavoltage irradiation yielded a high CR-rate in transitional cell bladder carcinoma patients with medium to severe early and late side effects. The value of such a combined treatment as far as the tumor eradication is concerned requires further evaluation, because of the small number of patients, the short follow-up, and the absence of other studies using docetaxel as a radiosensitizer in urothelial cell cancer.