Nipple- and areola-sparing mastectomy for the treatment of breast cancer

$\textbf{Background}$ The efficacy and safety of nipple-sparing mastectomy and areola-sparing mastectomy for the treatment of breast cancer are still questionable. It is estimated that the local recurrence rates following nipple-sparing mastectomy are very similar to breast-conserving surgery followed by radiotherapy. $\textbf{Objectives}$ To assess the efficacy and safety of nipple-sparing mastectomy and areola-sparing mastectomy for the treatment of ductal carcinoma in situ and invasive breast cancer in women. $\textbf{Search methods}$ We searched the Cochrane Breast Cancer Group's Specialized Register, the Cochrane Center Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), Embase (via OVID) and LILACS (via Biblioteca Virtual em Saúde [BVS]) using the search terms “nipple sparing mastectomy” and “areola-sparing mastectomy”. Also, we searched the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov. All searches were conducted on 30th September 2014 and we did not apply any language restrictions. $\textbf{Selection criteria}$ Randomised controlled trials (RCTs) however if there were no RCTs, we expanded our criteria to include non-randomised comparative studies (cohort and case-control studies). Studies evaluated nipple-sparing and areola-sparing mastectomy compared to modified radical mastectomy or skin-sparing mastectomy for the treatment of ductal carcinoma in situ or invasive breast cancer. $\textbf{Data collection and analysis}$ Two review authors (BS and RR) performed data extraction and resolved disagreements. We performed descriptive analyses and meta-analyses of the data using Review Manager software. We used Cochrane's risk of bias tool to assess studies, and adapted it for non-randomised studies, and we evaluated the quality of the evidence using GRADE criteria. $\textbf{Main results}$ We included 11 cohort studies, evaluating a total of 6502 participants undergoing 7018 procedures: 2529 underwent a nipple-sparing mastectomy (NSM), 818 underwent skin-sparing mastectomy (SSM) and 3671 underwent traditional mastectomy, also known as modified radical mastectomy (MRM). No participants underwent areola-sparing mastectomy. There was a high risk of confounding for all reported outcomes. For overall survival, the hazard ratio (HR) for NSM compared to SSM was 0.70 (95% CI 0.28 to 1.73; 2 studies; 781 participants) and the HR for NSM compared to MRM was 0.72 (95% CI 0.46 to 1.13; 2 studies, 1202 participants). Local recurrence was evaluated in two studies, the HR for NSM compared to MRM was 0.28 (95% CI 0.12 to 0.68; 2 studies, 1303 participants). The overall risk of complications was different in NSM when compared to other types of mastectomy in general (RR 0.10, 95% CI 0.01 to 0.82, 2 studies, P = 0.03; 1067 participants). With respect to skin necrosis, there was no evidence of a difference with NSM compared to other types of mastectomy, but the confidence interval was wide (RR 4.22, 95% CI 0.59 to 30.03, P = 0.15; 4 studies, 1948 participants). We observed no difference among the three types of mastectomy with respect to the risk of local infection (RR 0.95, 95% CI 0.44 to 2.09, P = 0.91, 2 studies; 496 participants). Meta-analysis was not possible when assessing cosmetic outcomes and quality of life, but in general the NSM studies reported a favourable aesthetic result and a gain in quality of life compared with the other types of mastectomy. The quality of evidence was considered very low for all outcomes due to the high risk of selection bias and wide confidence intervals. $\textbf{Authors' conclusions}$ The findings from these observational studies of very low-quality evidence were inconclusive for all outcomes due to the high risk of selection bias

Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer

BackgroundAn estimated 220,000 new cases of non-small cell lung cancer (NSCLC) and 160,000 deaths are expected to occur in the US in 2013, representing about 28% of cancer-related mortality. Approximately 75% of these people will have locally advanced or metastatic disease and will be treated in a palliative setting. Platinum-based combination chemotherapy has benefits in terms of survival and symptom control when compared with best supportive care.ObjectivesTo assess the efficacy and safety of carboplatin-based chemotherapy when compared with cisplatin-based chemotherapy, both in combination with a third-generation drug, in people with advanced NSCLC. To compare quality of life in people with advanced NSCLC receiving chemotherapy with cisplatin and carboplatin combined with a third-generation drug.Search methodsWe searched the following electronic databases: MEDLINE (via PubMed) (1966 to 6 March 2013), EMBASE (via Ovid) (1974 to 6 March 2013), Cochrane Central Register of Controlled Trials (CENTRAL; Issue 2, 2013), and LILACS (1982 to 6 March 2013). in addition, we handsearched the proceedings of the American Society of Clinical Oncology Meetings (January 1990 to March 2013), reference lists from relevant resources and the Clinical Trial.gov database.Selection criteriaRandomised clinical trials comparing regimens with carboplatin or cisplatin combined with a third-generation drug in people with locally advanced or metastatic NSCLC. We accepted any regimen and number of cycles that included these drugs, since there is no widely accepted standard regimen.Data collection and analysisTwo review authors independently assessed search results and a third review author resolved any disagreements. We analysed the following endpoints: overall survival, one-year survival, quality of life, toxicity and response rate.Main resultsWe included 10 trials with 5017 people, 3973 of whom were available for meta-analysis. There was no difference between carboplatin-based and cisplatin-based chemotherapy in overall survival (hazard ratio (HR) 1.00; 95% confidence interval (CI) 0.51 to 1.97, I-2 = 0%) and one-year survival rate (risk ratio (RR) 0.98; 95% CI 0.88 to 1.09, I-2 = 24%). Cisplatin had higher response rates when we performed an overall analysis (RR 0.88; 95% CI 0.79 to 0.99, I-2 = 3%), but trials using paclitaxel or gemcitabine plus a platin in both arms had equivalent response rates (paclitaxel: RR 0.89; 95% CI 0.74 to 1.07, I-2 = 0%; gemcitabine: RR 0.92; 95% CI 0.73 to 1.16, I-2 = 34%). Cisplatin caused more nausea or vomiting, or both (RR 0.46; 95% CI 0.32 to 0.67, I-2 = 53%) and carboplatin caused more thrombocytopenia (RR 2.00; 95% CI 1.37 to 2.91, I-2 = 21%) and neurotoxicity (RR 1.55; 95% CI 1.06 to 2.27, I-2 = 0%). There was no difference in the incidence of grade III/IV anaemia (RR 1.06; 95% CI 0.79 to 1.43, I-2 = 20%), neutropenia (RR 0.96; 95% CI 0.85 to 1.08, I-2 = 49%), alopecia (RR 1.11; 95% CI 0.73 to 1.68, I-2 = 0%) or renal toxicity (RR 0.52; 95% CI 0.19 to 1.45, I-2 = 3%). Two trials performed a quality of life analysis; however, they used different methods of measurement so we could not perform a meta-analysis.Authors' conclusionsThe initial treatment of people with advanced NSCLC is palliative, and carboplatin can be a treatment option. It has a similar effect on survival but a different toxicity profile when compared with cisplatin. Therefore, the choice of the platin compound should take into account the expected toxicity profile and the person's comorbidities. in addition, when used with either paclitaxel or gemcitabine, the drugs had an equivalent response rate.Brazilian Cochrane Center, BrazilFMUSP, ICESP, BR-01246000 São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, Escola Paulista Med, São Paulo, BrazilCtr Estudos Med Baseada Evidencias & Avaliacao Te, Brazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, Escola Paulista Med, São Paulo, BrazilWeb of Scienc