Frederico Leal

Neoadjuvant endocrine therapy for resectable breast cancer: A systematic review and meta-analysis

INTRODUCTION The role of neoadjuvant endocrine therapy for resectable breast cancer is not well established, despite encouraging results obtained in the metastatic and adjuvant settings. This systematic review aims to examine existing medical literature on neoadjuvant hormone therapy (HT). METHODS Data from prospective, randomized trials was included if comparing neoadjuvant HT versus surgery alone without adjuvant treatment, or neoadjuvant HT versus chemotherapy (CT), or HT plus CT versus CT alone, or HT plus CT versus HT alone, or two distinct HT. Odds Ratios (OR) were calculated from pooled data. RESULTS Five studies compared HT with tamoxifen versus HT with aromatase inhibitors (AI). A meta-analysis of their results demonstrated superiority of AIs in overall response rate (ORR) (OR 1.9; 95% CI 1.17-3.08). Two trials compared HT against CT, and pooled data from them demonstrated a trend favoring CT (OR for ORR 0.75; 95% CI 0.35-1.6). That trend disappeared when only postmenopausal women were considered (OR 1.01; 95% CI 0.62-1.63). One trial compared HT plus CT with no neoadjuvant treatment, and obtained an 83% ORR. One trial compared HT plus CT versus CT alone and found a non-significant increase in ORR for adding HT to CT (OR 1.48; 95% CI 0.58-3.77). No trial compared HT plus CT versus HT alone. CONCLUSIONS Neoadjuvant HT is a safe and feasible option, but it cannot be considered equivalent to CT. If neoadjuvant HT is performed, AIs are preferable over tamoxifen due to higher response rates.

Association between genetic polymorphisms in DNA mismatch repair-related genes with risk and prognosis of head and neck squamous cell carcinoma

We examined the influence of MLH1 c.−93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A and EXO1 c.1765G>A polymorphisms, involved in DNA mismatch repair (MMR), on head and neck (HN) squamous cell carcinoma (SCC) risk and prognosis. Aiming to identify genotypes, DNA from 450 HNSCC patients and 450 controls was analyzed by PCR‐RFLP or real time PCR. MSH2 GG plus MSH3 GG (31.7% vs. 18.7%, p = 0.003) genotypes were higher in laryngeal SCC (LSCC) patients than in controls. Carriers of the respective combined genotype were under a 3.69 (95% CI: 1.54–8.81)‐fold increased risk of LSCC. Interactions of tobacco and tobacco plus all the above‐mentioned polymorphisms on HNSCC and LSCC risk were also evident in study (p = 0.001). At 60 months of follow‐up, relapse‐free survival (RFS) was shorter in patients with EXO1 GG genotype (54.8% vs. 61.1%, p = 0.03) and overall survival (OS) was shorter in patients with MSH3 GG genotype (42.8% vs. 52.5%, p = 0.02) compared to those with other genotypes, respectively. After multivariate Cox analysis, patients with EXO1 GG and MSH3 GG genotypes had worst RFS (HR: 1.50, 95% CI: 1.03–2.20, p = 0.03) and OS (HR: 1.59, 95% CI: 1.19–2.13, P = 0.002) than those with the remaining genotypes, respectively. Our data present, for the first time, evidence that inherited MLH1 c.‐93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A, and EXO1 c.1765G>A abnormalities of DNA MMR pathway are important determinants of HNSCC, particularly among smokers, and predictors of patient outcomes.

Gemcitabine-related thrombotic microangiopathy: a single-centre retrospective series

Abstract Introduction: Thrombotic microangiopathy (TMA) has been reported as a complication of chemotherapy. Many antineoplastic agents have been linked to TMA, gemcitabine being one of the most frequently cited as related to this syndrome. Methods: A retrospective search for chemotherapy-induced TMA cases among gemcitabine users in a single oncology centre from January 2009 to September 2012 was performed. Results: Three cases of gemcitabine-induced TMA were reported, from a total of 264 patients (incidence: 1·13%) who received the drug. From the three cases reported, two (66%) patients died as a consequence of the syndrome. Discussion: These findings are compatible with previous analyses, which report an incidence of gemcitabine-associated TMA ranging from 0·008 to 2·2% and mortality rates from 15 to 90%. Unlike previously reported, however, cumulative dose was not predictive of risk. Conclusion: Gemcitabine-induced TMA is an underdiagnosed condition characterized by high mortality rates. Attention should be called for a higher level of awareness to provide early diagnosis and proper treatment.

Cost-effectiveness of cetuximab and panitumumab for chemotherapy-refractory metastatic colorectal cancer

Background Cetuximab and panitumumab are monoclonal antibodies targeting the epidermal growth factor receptor. Both drugs are active against RAS wild type metastatic colorectal cancer after chemotherapy failure, with similar efficacy and toxicity profiles. However, their cost and limited survival benefits may compromise incorporation in the Brazilian public healthcare system, the Unified Heath System (Sistema Único de Saúde) (SUS). Methods A cost-effectiveness analysis was conducted using a Markov model from the Brazilian Public health perspective and a lifetime horizon in patients with RAS -wt mCRC. Transition probabilities and mortality rates were extracted from randomized studies. Treatment costs were obtained from price tables regulated by the Brazilian Health Ministry. The World Health Organization recommendation of three times GDP per capita was used to define the cost-effectiveness threshold. Results The use of cetuximab or panitumumab for chemotherapy-refractory mCRC patients resulted in 0.22 additional life-years relative to BSC, with incremental cost-effectiveness ratios (ICERs) of

Optimal duration of androgen deprivation therapy following radiation therapy in intermediate- or high-risk non-metastatic prostate cancer: A systematic review and meta-analysis

58,240 and

Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma.

52,772 per LY, respectively. That exceeds the pre-specified threshold for cost-effectiveness. Acquisition of biological agents was the major driver of increased costs. Conclusions Our economic evaluation demonstrates that both cetuximab and panitumumab are not a cost-effective approach in RAS-wt mCRC patients. Discussion about drug price should be prioritized to enable incorporation of these monoclonal antibodies in the SUS.

OGG1, APEX1 and XRCC1 polymorphisms in oropharyngeal squamous cell carcinoma risk and prognosis.

ABSTRACT Objectives: To investigate current evidence on the optimal duration of adjuvant hormone deprivation for prostate cancer treated with radiation therapy with curative intent. Materials and Methods: A systematic search was performed in electronic databases. Data from randomized trials comparing different durations of hormone blockade was collected for pooled analysis. Overall survival, disease-free survival, disease-specific survival and toxicity were the outcomes of interest. Meta-analyses were performed using random-effects model. Results: Six studies met the eligibility criteria. For overall survival, the pooled data from the studies demonstrated a statistically significant benefit for longer hormone deprivation (Hazard Ratio 0.84; 95% CI 0.74 – 0.96). A statistically significant benefit was also found for disease-free survival (Hazard Ratio 0.74; 95% CI 0.62 – 0.89), and disease-specific survival (Hazard Ratio 0.73; 95% CI 0.62 – 0.85). Studies with longer blockade duration arm demonstrated greater benefit. Toxicity was low, with no increase in cardiovascular events. Conclusions: Longer duration of androgen deprivation combined to radiotherapy prolongs OS, DFS and DSS in patients with intermediate and high-risk non-metastatic prostate cancer. However, this evidence is based on trials using older radiation techniques, and further research of combination of androgen deprivation and new RT technologies may be warranted.