Identification of breast cancer patients with a high risk of developing brain metastases: a single-institutional retrospective analysis.

BACKGROUND: The objective of this study was to identify breast cancer patients with a high risk of developing brain metastases who may benefit from pre-emptive medical intervention. METHODS: Medical records of 352 breast cancer patients with local or locoregional disease at diagnosis were retrospectively analysed. The brain metastasis-free survival was estimated using the Kaplan-Meier method and patient groups were compared using the log rank test. The simultaneous relationship of multiple prognostic factors was assessed using Cox's proportional hazard regression analysis. The Fisher exact test was used to test the difference of proportions for statistical significance. RESULTS: On univariate analysis, statistically highly significant unfavourable risk factors for the brain metastasis-free survival were negative ER status, negative PR status, and triple negative tumor subtype. Young age at diagnosis (≤35 years) and advanced disease stage were not statistically significant (p = 0.10). On multivariate analysis, the only independent significant factor was the ER status (negative ER status; hazard radio (95% confidence interval), 5.1 (1.8-14.6); p = 0.003). In the subgroup of 168 patients with a minimum follow-up of 24 months, 49 patients developed extracranial metastases as first metastatic event. Of those, 7 of 15 (46.6%) with a negative ER status developed brain metastases compared to 5 of 34 (14.7%) with a positive ER status (Fisher exact test, p = 0.03). The median time interval (minimum-maximum) between the diagnosis of extracranial and brain metastases was 7.5 months (1-30 months). CONCLUSIONS: Breast cancer patients with extracranial metastasis and negative ER status exhibited an almost 50% risk of developing brain metastasis during their course of disease. Future studies are highly desired to evaluate the efficacy of pre-emptive medical intervention such as prophylactic treatment or diagnostic screening for high risk breast cancer patients.

Intensity modulated radiotherapy of upper abdominal malignancies: dosimetric comparison with 3D conformal radiotherapy and acute toxicity.

BACKGROUND: The goal of this study was to assess a possible dosimetric advantage of intensity modulated radiotherapy (IMRT) of upper abdominal malignancies compared to three-dimensional conformal radiotherapy (3DCRT), and to assess the impact of IMRT on acute toxicity. METHODS: Thirty-one unselected consecutive patients with upper abdominal malignancies were treated with definitive (n =16) or postoperative (n =15) IMRT. Twenty-one patients (67.7%) received concomitant chemotherapy. 3DCRT plans were generated for comparison, and analysis of variance (ANOVA) for repeated measurements was used to test for significant difference of dosimetric parameters. Acute toxicity was assessed weekly using the Common Terminology Criteria for Adverse Events (CTCAE) grading scale. RESULTS: IMRT plans showed a small but statistically significant improvement of the conformity index compared to 3DCRT plans (difference (95% confidence interval), -0.06 (-0.109 to-0.005); p = 0.03). The homogeneity index was not significantly improved (p = 0.10). A significantly reduced high dose volume on cost of a significantly increased low dose volume was observed for the kidneys. The acute toxicity appeared to be less than commonly reported for corresponding patients treated with 3DCRT. No patient developed grade 3 or 4 non-hematological acute toxicity, and the most common grade 2 toxicity was vomiting (9.7%). CONCLUSIONS: IMRT offers the potential of a clinically relevant dosimetric advantage compared to 3DCRT in terms of a reduced acute toxicity. Further optimization of the radiotherapy technique and more clinical trials are required before IMRT is routinely used for upper abdominal malignancies.