Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study.

BACKGROUND: Improvements in local control are required when using preoperative chemoradiation for cT4 or advanced cT3 rectal cancer. There is therefore a need to explore more effective schedules. PATIENTS AND METHODS: Patients with fixed cT3 or cT4 cancer were randomized either to 5 × 5 Gy and three cycles of FOLFOX4 (group A) or to 50.4 Gy in 28 fractions combined with two 5-day cycles of bolus 5-Fu 325 mg/m(2)/day and leucovorin 20 mg/m(2)/day during the first and fifth week of irradiation along with five infusions of oxaliplatin 50 mg/m(2) once weekly (group B). The protocol was amended in 2012 to allow oxaliplatin to be then foregone in both groups. RESULTS: Of 541 entered patients, 515 were eligible for analysis; 261 in group A and 254 in group B. Preoperative treatment acute toxicity was lower in group A than group B, P = 0.006; any toxicity being, respectively, 75% versus 83%, grade III-IV 23% versus 21% and toxic deaths 1% versus 3%. R0 resection rates (primary end point) and pathological complete response rates in groups A and B were, respectively, 77% versus 71%, P = 0.07, and 16% versus 12%, P = 0.17. The median follow-up was 35 months. At 3 years, the rates of overall survival and disease-free survival in groups A and B were, respectively, 73% versus 65%, P = 0.046, and 53% versus 52%, P = 0.85, together with the cumulative incidence of local failure and distant metastases being, respectively, 22% versus 21%, P = 0.82, and 30% versus 27%, P = 0.26. Postoperative and late complications rates in group A and group B were, respectively, 29% versus 25%, P = 0.18, and 20% versus 22%, P = 0.54. CONCLUSIONS: No differences were observed in local efficacy between 5 × 5 Gy with consolidation chemotherapy and long-course chemoradiation. Nevertheless, an improved overall survival and lower acute toxicity favours the 5 × 5 Gy schedule with consolidation chemotherapy. CLINICAL TRIAL NUMBER: The trial is registered as ClinicalTrials.gov number NCT00833131.

Male breast cancer. Does the prognosis differ compared to female?

Due to the low incidence of breast cancer in males there are not many reports in the literature. In this study we analyzed results of treatment in 65 breast cancer males, who had been treated in one institution. Radical surgery was performed in 45 patients. Lymph node metastases were found in 25 patients (55.5%), the tumor was usually moderately differentiated (21 pts - 46.7%). Median survival after radical surgery was 73 months compared to 38 months for nonsurgical patients (p < 0.0001). In the group of males after radical surgery the results of 5-, 10- and 15-year survival rates were 69.8, 59.7 and 31.3% respectively. Comparable analysis of two subgroups of patients with favorable (T1 or T2, N0, grade I or II) and unfavorable (T3 or N+ or grade III) prognostic factors was also performed. In the first subgroup the 5-, 10- and 15-year survival rates were 90, 77.4 and 62%, compared to 61.8, 23.1 and 23. 1% for the second subgroup. The multivariate analysis showed grading and node status as the strongest parameters influencing survival. Relative risk of death was over 3 times higher for nodal metastases and near 3 times higher for high grade carcinomas (p < 0.01), compared to patients without metastases and low grade of tumor. Similar analysis was performed when 45 males were compared to 500 selected women, with similar clinical parameters (age, node status, grading). Again, data indicated grading and lymph node status as the strongest prognostic factors. It was not unlikely, that gender had some influence on prognosis, when relative risk of death for males was over 1.5 times higher than for females, but this result was not clearly significant (p < 0.1 ). The question, whether male breast cancer prognosis is worse then in female remains open. Multiinstitutional prospective studies are needed in this area.