Evaluation of efficacy and toxicity in two different hypofractionated 3D-conformal external beam radiotherapy schedules in localised muscle invasive bladder cancer.

PURPOSE: To evaluate the efficacy as well as acute and late toxicity of two different accelerated hypofractionated 3D-conformal radiotherapy (Hypo-3DCRT) schedules in patients with bladder cancer. METHODS: Between February 2006 and June 2011, 50 elderly patients with cT1-2N0 bladder carcinoma were treated with Hypo-3DCRT. Mean age was 75 years. All patients were medically inoperable, with poor performance status, who couldn't tolerate either cystectomy or radical external beam irradiation on a daily basis. A dose of 36 Gy in 6 weekly fractions (arm A, N=39) or 39.96 Gy of 3.33 Gy twice daily, once a week, for 6 weeks (arm B, N=11) were prescribed. The primary study endpoints were the evaluation of acute/late gastrointestinal (GI) toxicity according to the EORTC/RTOG scale together with the visual analogue bladder-related pain score (VAS). RESULTS: The GI acute toxicities were: grade 1: arm A 24/39 (61.5%), arm B 9/11 (81.8%); grade 2: arm A 14/39 (35.9%), arm B 1/11 (9.1%); grade 3: arm A 1/39 (9.1%) (x(2), p=0.29). Only grade 1 late GI toxicity was seen and was significantly higher in arm A: arm A 17/39 (43.6%) and arm B 1/11 (9.1%) (x(2), p=0.037). The reduction of VAS score was similar in both arms (p=0.065). The median relapse free survival (RFS) was 15 and 16 months for arm A and B, respectively (log rank, p=0.71). CONCLUSIONS: Beyond the non-randomized design of the trial, the Hypo-3DCRT schedules used appear to be an acceptable alternative to the traditional longer radiotherapy (RT) schedules for elderly patients unfit for daily irradiation.

Rapid improvement of extensive non-melanoma skin cancers with combination of 13-cis-retinoic acid and radiotherapy: report of three cases.

Extensive non-melanoma skin cancer (NMSC) constitutes a therapeutic challenge especially in old and debilitated patients. Applied treatments include surgical excision, MOHS micrographic surgery, cryosurgery, electrodesiccation, and radiotherapy. We present 3 elderly patients with extensive basal or squamous cell carcinomas and poor general condition who were treated with a combination of 13-cis-retinoic acid 1 mg/kg daily and radiotherapy 2.5 Gy daily. The treatment resulted in rapid improvement of the tumors with significant reduction of their size.

Evaluation of the possible benefits of post-radiotherapy surgery after concomitant chemoradiotherapy with a new radio-sensitizing regimen (irinotecan / CPT-11, interferon A2b and amifostine) for advanced-stage cervical carcinoma. Preliminary results of a pilot phase-II study.

PURPOSE: This phase II pilot study was conducted to evaluate the results of a three-modality approach (which included post-chemoradiotherapy surgery) in advanced-stage cervical carcinomas. PATIENTS AND METHODS: Thirty-six patients underwent either surgery or were put on follow-up after having received radical cervical radiotherapy (RT) combined with radiosensitizing chemoimmunotherapy with irinotecan (CPT-11), interferon (IFN) A2b, and amifostine. The last selection (surgery or follow-up) was based on clinical evaluation (downstaged or not). Feasibility, morbidity, surgical outcome and survival were evaluated. RESULTS: Twenty-six patients had stage IIb and 10 IIIb disease at diagnosis. Sixteen (44%) were clinically downstaged, thus becoming eligible for surgery. Twelve (33%) were operated and the others were put on follow-up. There was no significant increase in treatment-related morbidity of the group of patients receiving three-modality therapy, since only one intraoperative complication had occurred. In 58% of the operated patients, chemoradiotherapy-resistant tumor was found on pathology of the cervical specimens, while 29% of them had lymph nodes infiltrated by the tumor. After a median follow-up of 42.5 months, overall survival (OS) of operated vs. non-operated patients (88 vs. 56%, respectively) show only a trend toward significance (p=0.10). The overall recurrence/metastasis rate was 36.1% and the disease-free survival (DFS) 56% for operated vs. 76% for non-operated patients, respectively (p=0.63). CONCLUSION: These results indicate that post-chemoradiotherapy surgery is justified because of the high rate of residual disease found. Morbidity can be effectively limited with proper patient selection. A considerable survival benefit is expected, although this remains to be confirmed with phase III studies.

Radiation dermatitis: implicated factors, clinical aspects, possible prevention, and medical care.

The increasing incidence of cancer is due to many factors. Among them quite significant is considered the rising proportion of older people in the population and the modern methods of early diagnosis. Radiotherapy (RT), along with surgery and chemotherapy, is a major therapeutic modality in the management of cancer. In the context of current treatment methods and practice, approximately half of the patients with cancer will receive RT at some stage of their illness. RT can lead to cure some kinds of cancer but it can also be delivered for palliation. Unfortunately, skin damage is a complication affecting by and large all patients receiving external beam RT. In order to minimize the risk of this damage it would be helpful to know the complex underlying molecular mechanisms and evaluate the related clinical symptoms, not only for medical but also for psychological reasons related to the patient. The purpose of this article was to review the current approaches to this particular clinical condition, in order to realize an effective patient-oriented clinical practice and keep this radiation-induced complication as low as possible.

Phase I study of postoperative radiotherapy with concomitant weekly irinotecan, 5- fluorouracil and folinic acid in locally advanced rectal cancer.

PURPOSE: 5- fluorouracil (5-FU)-based chemotherapy with concomitant pelvic radiotherapy represents the gold standard of the adjuvant treatment of high-risk rectal cancer. This study aimed to determine the maximum tolerated dose (MTD) of weekly irinotecan (CPT-11) when combined with fixed 5FU/FA doses and pelvic irradiation. PATIENTS AND METHODS: Twenty- four patients with stage II or III rectal cancer were accrued. All had undergone curative surgery before entering the study. Standard pelvic radiotherapy was delivered (50.4 Gy, 1.8 Gy/ fraction in 5.5 weeks). The 5-FU/FA doses were 350/250 (mg/m(2)) in the first 6 patients and 250/100 in the remaining patients. Weekly doses of CPT-11 started at 30 mg/m(2) with escalation steps of 10 mg/m(2). CPT-11 was escalated when 3 patients had been monitored for 8 weeks, without a dose limiting toxicity (DLT). RESULTS: Twenty-three out of 24 patients completed the chemoradiation course. Only 1 patient discontinued the treatment due to persistent grade 3 diarrhea. Of the 144 planned weekly chemotherapy cycles, only 7 were omitted as a result of persisting grade 2-3 gastrointestinal toxicity in 3 patients and grade 3 neutropenia in 1 patient. Grade 3 gastrointestinal DLTs were observed at doses at the level of 30/250/100 in 1 patient and 70/250/100 in 2 patients. Late DLTs were severe radiation dermatitis and colitis at 40/ 350/250 (1 patient) and 70/250/100 (2 patients), respectively. With a follow-up of 18 months 20 (83.3%) patients remain disease- free. CONCLUSION: The administration of weekly CPT-11/ 5FU/FA with concomitant pelvic radiotherapy is feasible and effective. This treatment schedule is associated with mild myelosuppression and mild to moderate gastrointestinal toxicity. Caution should be paid on late radiotherapy-induced toxicities. The MTD of weekly CPT-11 is 30 mg/m(2) when combined with 5FU/FA doses (mg/m(2)) of 350sol;250 and reaches 60 mgsol;m(2) with lower doses of 5FU/FA (250/100).