Breast cancer patients with brain metastases or leptomeningeal disease: 10-year results of a national cohort with validation of prognostic indexes.

Development of brain metastasis (BM) and leptomeningeal (LM) disease in breast cancer (BC) patients indicates poor prognosis and impairs patients' quality of life. Prognostic survival scores for BM can help predict expected survival in order to choose the most appropriate treatment. The aim of our study was to analyze national data for BC patients treated with radiation therapy for BM/LM disease and validate the applicability of different survival prognostic scores. We retrospectively evaluated medical records of 423 BC patients with BM/LM disease receiving radiation therapy between April 2005 and December 2015. Patients were classified by BC Recursive Partitioning Analysis (B-RPA), Breast Graded Prognostic Assessment (Breast-GPA), Modified Breast Graded Prognostic Assessment (MB-GPA), and Simple Survival score for patients with BM from BC (SS-BM). Overall survival (OS) was calculated from the development of BM/LM disease to death or last follow-up date. After a median follow-up of 7.5 years, the median OS was 6.9 months (95% CI 5.5-7.8, range 0-146.4) and 1- and 2-year survival rates were 35% and 17%, respectively. Survival analysis showed significant differences in median OS regarding biologic subtypes (P < 0.0001), as follows: 3.2 (95% Confidence Interval (CI) 2.5-3.9), 3.9 (95% CI 2.3-5.6), 7.1 (95% CI 4.3-9.8), 12.1 (95% CI 8.3-15.9), and 15.4 (95% CI 8.8-22.1) months for primary triple-negative BC (TNBC), Luminal B HER2-negative, Luminal A, HER2-enriched, and Luminal B HER2-positive tumors, respectively. Good Karnofsky Performance Status (KPS), single metastasis, and absence of LM or extracranial disease all demonstrated better OS in univariate and multivariate analysis. All four employed prognostic indexes provided good prognostic value in predicting survival. SS-BM and MB-GPA showed the best discriminating ability (Concordance indexes C were 0.768 and 0.738, respectively). This study presents one of the largest single-institution series validating prognostic scores for BC patients with BM/LM. SS-BM and MB-GPA proved to be useful tools in the clinical decision-making process.

Induction chemotherapy, chemoradiotherapy and consolidation chemotherapy in preoperative treatment of rectal cancer - long-term results of phase II OIGIT-01 Trial.

Background The purpose of the study was to improve treatment efficacy for locally advanced rectal cancer (LARC) by shifting half of adjuvant chemotherapy preoperatively to one induction and two consolidation cycles. Patients and methods Between October 2011 and April 2013, 66 patients with LARC were treated with one induction chemotherapy cycle followed by chemoradiotherapy (CRT), two consolidation cycles, surgery and three adjuvant capecitabine cycles. Radiation doses were 50.4 Gy for T2-3 and 54 Gy for T4 tumours in 1.8 Gy daily fraction. The doses of concomitant and neo/adjuvant capecitabine were 825 mg/m2/12h and 1250mg/m2/12h, respectively. The primary endpoint was pathologic complete response (pCR). Results Forty-three (65.1%) patients were treated according to protocol. The compliance rates for induction, consolidation, and adjuvant chemotherapy were 98.5%, 93.8% and 87.3%, respectively. CRT was completed by 65/66 patients, with G ≥ 3 non-hematologic toxicity at 13.6%. The rate of pCR (17.5%) was not increased, but N and the total-down staging rates were 77.7% and 79.3%, respectively. In a median follow-up of 55 months, we recorded one local relapse (LR) (1.6%). The 5-year disease-free survival (DFS) and overall survival (OS) rates were 64.0% (95% CI 63.89-64.11) and 69.5% (95% CI 69.39-69.61), respectively. Conclusions In LARC preoperative treatment intensification with capecitabine before and after radiotherapy is well tolerated, with a high compliance rate and acceptable toxicity. Though it does not improve the local effect, it achieves a high LR rate, DFS, and OS.