Predictive and Prognostic Value of BRAF and NRAS Mutation of 159 Sentinel Lymph Node Cases in Melanoma—A Retrospective Single-Institute Study

Purpose: To assess the prognostic role of sentinel lymph node status (SLN) in melanoma patients, a statistical comparison was performed with the application of already known prognostic factors, mutational occurrence of BRAF and NRAS in the primary tumor, as well as disease outcome. Methods: Our retrospective single-center study involved 159 melanoma cases, who underwent SLN biopsy. The following clinico-pathological data were collected: age, gender, location of primary tumor, Breslow thickness, ulceration degree, histological subtype, mitosis count, lymphovascular and perineural invasion, presence of tumor-infiltrating lymphocytes, regression signs, mutations of BRAF and NRAS of the primary tumors, and SLN status. Results: From the studied clinico-pathological factors, only Breslow thickness increased the risk of SLN positivity (p = 0.025) by multivariate analysis, while neither BRAF nor NRAS mutation of the primary tumor proved to be a predictor of the SLN status. While the NRAS-mutant subgroup showed the most unfavorable outcome for progression-free and distant metastasis-free survival, their rate of positive SLNs proved to be relatively lower than that of patient groups with BRAF mutation and double-wild-type phenotypes. Conclusion: Similarly to the importance of SLN positivity, NRAS mutation of the primary tumor proved to be an independent prognostic factor of progression. Therefore, despite negative SLN, this NRAS-mutant subgroup of patients still requires closer monitoring to detect disease progression

The role of radiotherapy in the conservative treatment of ductal carcinoma in situ of the breast.

Breast-conserving surgery (BCS) followed by radiotherapy (RT) has become the standard of care for the treatment of early-stage (St. I-II) invasive breast carcinoma. However, controversy exists regarding the value of RT in the conservative treatment of ductal carcinoma in situ (DCIS). In this article we review the role of RT in the management of DCIS. Retrospective and prospective trials and meta-analyses published between 1975 and 2007 in the MEDLINE database, and recent issues of relevant journals/handbooks relating to DCIS, BCS and RT were searched for. In retrospective series (10,194 patients) the 10-year rate of local recurrence (LR) with and without RT was reported in the range of 9-28% and 22-54%, respectively. In four large randomised controlled trials (NSABP-B-17, EORTC-10853, UKCCCR, SweDCIS; 4,568 patients) 50 Gy whole-breast RT significantly decreased the 5-year LR rate from 16-22% (annual LR rate: 2.6-5.0%) to 7-10% (annual LR rate: 1.3-1.9%). In a recent meta-analysis of randomised trials the addition of RT to BCS resulted in a 60% risk reduction of both invasive and in situ recurrences. In a multicentre retrospective study, an additional dose of 10 Gy to the tumour bed yielded a further 55% risk reduction compared to RT without boost. To date, no subgroups have been reliably identified that do not benefit from RT after BCS. In the NSABP-B-24 trial, the addition of tamoxifen (TAM) to RT reduced ipsilateral (11.1% vs. 7.7%) and contralateral (4.9% vs. 2.3%) breast events significantly. In contrast, in the UKCCCR study, TAM produced no significant reduction in all breast events. Based on available evidence obtained from retrospective and prospective trials, all patients with DCIS have potential benefit from RT after BCS. Further prospective studies are warranted to identify subgroups of low-risk patients with DCIS for whom RT can be safely omitted. Until long-term results of ongoing studies on outcomes of patients treated with BCS alone (with or without TAM or aromatase inhibitors) are available, RT should be routinely recommended after BCS for all patients except those with contraindication