The GETUG SEMITEP Trial: De-escalating Chemotherapy in Good-prognosis Seminoma Based on Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

BACKGROUND: In metastatic seminoma, a strategy is needed for selecting patients for less intensive chemotherapy, to limit toxicities. OBJECTIVE: To assess whether men with good-prognosis metastatic seminoma could be treated with two cycles of etoposide-cisplatin (EP) followed by only one cycle of carboplatin (CARBO) based on negative interim fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT). DESIGN, SETTING, AND PARTICIPANTS: A nonrandomised, multicentre, phase 2 trial was conducted (NCT01887340). INTERVENTION: All patients with baseline-positive FDG-PET/CT received EP for two cycles. After completing the first two cycles, the patients underwent a second FDG-PET/CT to assess the response. Patients with positive FDG-PET/CT proceeded directly to two additional EP cycles; those who achieved FDG-PET/CT negativity received one cycle of CARBO. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The proportion of patients with negative interim FDG-PET/CT who received carboplatin was determined. RESULTS AND LIMITATIONS: Between 2013 and 2017, 102 patients were enrolled. After the first two EP cycles, FDG-PET/CT was available in 98 patients. Overall, 67 patients (68.4%; 95% confidence interval [CI]: 58.2-77.4) had negative FDG-PET/CT and proceeded to a single CARBO cycle. Twenty-seven patients (27.6%; 95% CI: 19.0-37.5) had positive FDG-PET/CT after two EP cycles. The 3-yr progression-free survival rate was 90.0% (95% CI: 74.4-96.5) in the EP group and 90.8% (95% CI: 81.4-95.7) in the CARBO group. The cumulative incidences of peripheral neuropathy and ototoxicity were significantly higher in the EP group. CONCLUSIONS: Omission of two cycles of EP based on negative FDG-PET/CT after two cycles of chemotherapy appears to be feasible. However, the absence of consensus criteria for FDG-PET/CT interpretation and the short follow-up need additional studies. This strategy does not warrant routine integration yet. PATIENT SUMMARY: Men with good-prognosis metastatic seminoma were treated with fewer cycles of chemotherapy based on interim fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). Omission of two cycles of chemotherapy based on negative FDG-PET/CT after two initial cycles appears to be feasible, thereby limiting the burden of treatment and toxicity.

Synthesis of Kisspeptin-Mimicking Fragments and Investigation of their Skin Anti-Aging Effects.

In recent years, a number of active materials have been developed to provide anti-aging benefits for skin and, among them, peptides have been considered the most promising candidate due to their remarkable and long-lasting anti-wrinkle activity. Recent studies have begun to elucidate the relationship between the secretion of emotion-related hormones and skin aging. Kisspeptin, a neuropeptide encoded by the KISS1 gene, has gained attention in reproductive endocrinology since it stimulates the reproductive axis in the hypothalamus; however, the effects of Kisspeptin on skin have not been studied yet. In this study, we synthesized Kisspeptin-10 and Kisspeptin-E, which are biologically active fragments, to mimic the action of Kisspeptin. Next, we demonstrated the anti-aging effects of the Kisspeptin-mimicking fragments using UV-induced skin aging models, such as UV-induced human dermal fibroblasts (Hs68) and human skin explants. Kisspeptin-E suppressed UV-induced 11 beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) stimulation leading to a regulation of skin aging related genes, including type I procollagen, matrix metalloproteinases-1 (MMP-1), interleukin-6 (IL-6), and IL-8, and rescued the skin integrity. Taken together, these results suggest that Kisspeptin-E could be useful to improve UV-induced skin aging by modulating expression of stress related genes, such as 11ß-HSD1.

[Infiltrating breast cancer in women younger than 25 years: 13 cases]. / Cancer du sein infiltrant chez les femmes de moins de 25 ans. A propos de 13 cas.

OBJECTIVE: To study the prognosis of breast cancer in woman younger than 25 years and to compare it with that of other age groups to identify prognostic and histologic factors specific to this group. METHOD: Retrospective study of all cases of infiltrating ductal carcinoma treated at our hospital from January 1977 through July 2005, examining clinical, histologic, and treatment variables as well as 5-year overall survival and 5-years disease-free survival rates. RESULTS: The study included 13 women younger than 25 years at diagnosis. Their average age at diagnosis was 23.3 years (CI=1 year). Time from initial signs of disease until diagnosis averaged 6.6 months (CI=2.5). Clinically, the average tumor size was 28.78 mm (CI=6.06), with 46% classified as T1, 31% as T2 and 23% as T4d. We found 92.3% to be invasive ductal carcinoma, with 30% including an in-situ component; 53.8% were SBR grade 3 and 23% included axillary node invasion. Hormone receptors were present in 61.5% of tumors. During the follow-up period, we observed two deaths (with a 5-year overall survival rate, however, of 91%) and 6 recurrences (5-year disease-free survival: 66.5%). CONCLUSION: Prognosis appears unfavorable among young women (younger than 40 years) with breast cancer. In our series, neither prognosis nor clinical or histologic characteristics differed in the subgroup of very young women (younger than 26 years).