Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

Spatial assessment and source identification of trace metal pollution in stream sediments of Oued El Maadene basin, northern Tunisia.

An extensive spatial survey was conducted on trace metal content in stream sediments from Oued El Maadene basin, northern Tunisia. Our objectives were to evaluate the level of trace metal pollution and associated ecological risk and identify the major sources of metal pollution. A total of 116 stream sediment samples were collected and analysed for total As, Cd, Cr, Cu, Ni, Pb, V, Zn, and Zr concentrations. The results showed that concentrations of Cr, Ni, V, and Zr were close to natural levels. In contrast, As, Cd, Cu, Pb, and Zn had elevated concentrations and enrichment factors compared to other contaminated regions in northern Tunisia. Ecological risk to aquatic ecosystems was highlighted in most areas. Principal component analysis showed that Cr, Ni, V, and Zr mainly derived from local soil and bedrock weathering, whilst As, Cd, Pb, and Zn originated from mining wastes. Trace metals could be dispersed downstream of tailings, possibly due to surface runoff during the short rainy season. Surprisingly, Cu, and to a lesser extent As, originated from agricultural activities, related to application of Cu-based fungicides in former vineyards and orchards. This study showed that, despite the complete cessation of mining activities several decades ago, metal pollution still impacts the local environment. This large pollution, however, did not mask other additional sources, such as local agricultural applications of fungicides.