Abstract: AIMS AND BACKGROUND: To compare conventional fractionation (CF) radiation therapy (RT), arm A, versus a split-course accelerated hyperfractionated schedule (S-AHF), arm B, versus CFRT plus concomitant chemotherapy (CT), arm C, in terms of five-year survival and toxicity for squamous cell tumors of the oropharynx. METHODS AND STUDY DESIGN: Between January 1993 and June 1998, 192 previously untreated patients with stage III and IV oropharyngeal carcinoma (excluding T1N1 and T2N1) were enrolled in a multicenter randomized phase III trial (ORO 93-01). In arms A and C, 66 to 70 Gy in 33 to 35 fractions was administered five days a week for six and a half to seven weeks. In arm B, the dose delivered was 64 to 67.2 Gy in two fractions of 1.6 Gy every day, five days a week, with a planned two-week split at 38.4 Gy. In arm C the CT regimen consisted of three cycles of carboplatin and 5-fluorouracil (CBDCA 75 mg/m2 on days 1 to 4 and 5-FU 1000 mg/m2 i.v. on days 1 to 4 every 28 days). RESULTS: No statistically significant difference was found in five-year overall survival (P = 0.39): 21% for arm A, 21% for arm B, and 40% for arm C. Similarly, there was no statistically significant difference in terms of five-year relapse-free survival: 15% for arm A, 17% for arm B, and 36% for arm C. There was a slight trend towards better five-year locoregional control (P = 0.07) for the combined arm: patients without locoregional relapse were 48% in arm C, 21% in arm A and 18% in arm B. Locoregional control was significantly better when arm C was compared with arms A and B combined (P = 0.02; arm A+B 20%; arm C 48%). Distant metastases were fairly balanced in the three arms (A: 14; B: 9; C: 11), with a tendency towards more frequent isolated distant metastasis development in arm C (8 of 11 [72%] versus 7 of 23 [30%] in arms A+B). Five-year second-tumor-free survival was 85%. The 13 second tumors were equally distributed and were mainly correlated with tobacco and alcohol consumption (five lung, two esophagus, two oral cavity, one larynx, one pancreas, one hepatocarcinoma, one myeloma). Arm C showed slightly more G3+ late side effects involving subcutaneous tissues and mucosa, although significant late sequelae were relatively uncommon and the mucosal side effects were mostly transient. The occurrence of persistent G3 xerostomia was comparable in the three treatment arms. CONCLUSIONS: The results obtained with the combination of CT and RT compared with RT alone did not reach statistical significance, but combined treatment almost doubled the five-year overall survival, relapse-free survival and locoregional control rate. Patients with advanced squamous cell carcinomas of the oropharynx who are medically suitable for the combined approach should be treated with a combination of radiotherapy and chemotherapy. The occurrence of second tumors is relatively common in these patients and may contribute substantially to the causes of death.

Abstract: PURPOSE: To compare conventional fractionation radiation therapy (RT), Arm A, vs. split-course accelerated hyperfractionated RT (S-AHF), Arm B, vs. conventional fractionation RT plus concomitant chemotherapy (CT), Arm C, in terms of survival and toxicity for advanced, unresectable epidermoid tumors of oropharynx. METHODS AND MATERIALS: Between January 1993 and June 1998, 192 previously untreated patients affected with Stage III and IV oropharyngeal carcinoma (excluding T1N1 and T2N1) were accrued in a multicenter, randomized Phase III trial (ORO 93-01). For Arms A and C, 66-70 Gy in 33-35 fractions, 5 days a week, were administered in 6.5-7 weeks to tumor and positive nodes. In Arm B, the dose delivered to tumor and involved nodes was 64-67.2 Gy, giving 2 fractions of 1.6 Gy every day with an interfraction interval of at least 4 h and preferably 6 h, 5 days a week. At 38.4 Gy, a 2-week split was planned; after the split, RT was resumed with the same modality. In Arm C, CT regimen consisted of carboplatin and 5-fluorouracil (CBDCA 75 mg/m(2), Days 1-4; 5-FU 1,000 mg/m(2) i.v. over 96 h, Days 1-4, recycling every 28 days (at 1st, 5th, and 9th week). RESULTS: No statistically significant difference was detected in overall survival (p = 0.129): 40% Arm A vs. 37% Arm B vs. 51% Arm C were alive at 24 months. Similarly, there was no statistically significant difference in terms of event-free survival (p = 0.196): 20% for Arm A, 19% for Arm B, and 37% for Arm C were event free at 24 months. On the contrary, the 2-year disease-free survival was significantly different among the three arms (p = 0.022), with a superiority for Arm C. At 24 months, the proportion of patients without relapse was 42% for Arm C vs. 23% for Arm A and 20% for Arm B. Patients in Arm A less frequently developed G3+ acute mucositis than their counterparts in Arm B or C (14.7% vs. 40.3% vs. 44%). Regarding the CT-related acute toxicity, apart from 1 case of fatal nephrotoxicity, only hematologic G3+ (Grade 3 or higher) acute sequelae were observed (World Health Organization scale), most commonly leukopenia (22.7%). Arm C showed slightly more G3+ skin, s.c. tissue, and mucosal late side effects (RTOG scale), although significant sequelae were relatively uncommon, and mucosal sequelae were most commonly transient. The occurrence of persistent G3 xerostomia was comparable in all three treatment arms. CONCLUSIONS: The combination of simultaneous CT and RT with the regimen of this trial is better than RT alone in advanced oropharyngeal squamous-cell carcinomas, by increasing disease-free survival. This improvement, however, did not translate into an overall survival improvement, and was associated with a higher incidence of acute morbidity.

Abstract: PURPOSE: To quantify the possible advantages arising from the use of 'conformal' radiotherapy of localized prostate cancer, and to compare the dose distributions obtained with two different 'conformal' techniques. PATIENTS AND METHODS: Twelve patients with localized prostate cancer were enrolled in the study. For each patient, three techniques were planned: the standard 'box technique' (A), a four-fields 'conformal' technique (B), and a 6-fields conformal technique (C). For each of the 36 3D plans, dose-volume histograms (DVH) were obtained, along with the mean, maximum and minimum doses for the clinical and planning target volumes (CTV, PTV) for the rectum, the bladder, and the femoral heads. The resulting data were compared. RESULTS: On average, the standard technique resulted in the exposure of a significantly larger bladder volume to the higher doses; a similar, but less remarkable difference has been observed for the rectal volume. The coverage of the PTV appears to be significantly more homogeneous with the two conformal techniques. CONCLUSIONS: The results presented here add to the evidence available in the literature and suggest a possible advantage of both the conformal techniques over the standard 'box technique' for the treatment of localized prostate cancer. The 6-field conformal technique does not seem superior to the four field one.

Abstract: PURPOSE: This retrospective study aims to define the effects of different radiation dose levels on survival, local control and toxicity in a series of 208 patients with localised prostate cancer consecutively treated with radical radiation therapy. PATIENTS AND METHODS: From 1982 through 1996, 365 patients with prostate cancer have been consecutively treated with radical radiotherapy in Florence (n = 306) and Arezzo (n = 59). The 208 cases treated until January 1994 with Stage B (125/208, 60%) and C (83/208, 40%) are the objects of the present study. The treatment was most often limited to the prostatic area (81%), using a four-field "box technique" and 25 MV photon beams, up to a total dose of 60-65 Gy (21% of the patients), of 66-69 Gy (26%) and of 70 Gy (53%); conventional fractionation was used (fractional dose: 2 Gy; five fractions/week). Hormonal therapy was also given to 39% of the cases. The possible relationship between dose, stage, grading and survival has been analysed. The survival figures and the types of relapse observed (prostatic, lymphnodal or "biochemical") have been analysed also according to the extent of the target volume and to the prostate-specific antigen (PSA) value at diagnosis, in the entire series or in selected subgroups. RESULTS: In the whole series and also after radiation alone, the patients with Stage B, with more differentiated tumours and those treated with higher doses to the prostate obtained significantly better survival results. Multivariate analysis confirmed that the dose level has an independent prognostic value. The use of a limited target volume did not produce an excess of pelvic lymphnodal failures. Among the patients more recently treated with radiation alone, the PSA level at diagnosis is strongly related with the risk of local and "biochemical" failure, and also with the relapse-free survival. Toxicity was acceptable, also for the patients treated with higher doses, but late treatment-related damage is more frequent in patients treated on larger volumes. CONCLUSION: The results of this retrospective analysis confirm the good results of small volume, high dose radiation therapy of prostatic cancer, even taking into account the possible biases due to the retrospective nature of the study, and the relevance of the PSA level at diagnosis to define the risk of local failure.