Genetic landscape of indolent and aggressive Kaposi sarcomas.

BACKGROUND: Kaposi sarcoma (KS) is a rare skin tumour caused by herpesvirus 8 infection and characterized by either indolence or an aggressive course necessitating systemic therapies. The genetic basis of this difference remains unknown. OBJECTIVES: To explore the tumour mutational burden in indolent and aggressive KS. METHODS: We performed whole-exome sequencing on a cohort of 21 KS patients. We compared genetic landscape including tumor mutational burden between the two forms of indolent and agressive KS. RESULTS: Aggressive KS tumours had a significantly higher TMB and a larger cumulative number of deleterious mutations than indolent KS tumours. In addition, all aggressive tumours had at least three deleterious mutations, whereas most indolent tumours harboured only one or no predicted deleterious mutations. Deleterious mutations listed in the Cancer Gene Census were detected exclusively in patients with aggressive disease. An analysis of somatic copy-number alterations (SCNA) revealed a tendency towards higher number of alterations in aggressive KS. CONCLUSIONS: These data suggest that SCNA alterations and an increase in mutational burden promote aggressive KS and that it might be more appropriate to consider indolent KS as an opportunistic skin disease rather than a cancer.

Impact of adjuvant treatment modalities on the management of patients with stages I-II endometrial stromal sarcoma.

PURPOSE: To explore whether adjuvant treatment options may impact on the prognosis in localized endometrial stromal sarcomas (ESSs; stages I and II). The historical options usually discussed in addition to hysterectomy and bilateral salpingoophorectomy (BSO) are active surveillance, pelvic radiotherapy, chemotherapy and hormonal therapy, alone or in combination. PATIENTS AND METHODS: Among 84 consecutive patients treated for ESS at a single referral center, 54 with localized stage disease were identified. Recurrence-free survival and overall survival were estimated and patterns of recurrences described. Univariate and multivariate analyses were carried out. RESULTS: With a median follow-up of 58 months, only one patient had died. None of the 23 patients who had received adjuvant therapy relapsed compared with 13 of 31 patients who had not received any adjuvant therapy. Adjuvant treatments were hormonal therapy (n = 10) and brachytherapy with/without pelvic radiotherapy (n = 13). Almost the majority of relapses were local (92%) and extra-pelvic metastasis was observed in nearly half of the patients (46%). In the multivariate analysis, the major determinants of relapse-free survival were adjuvant treatment, myometrial invasion (P = 0.005) and no BSO (P = 0.005). CONCLUSIONS: In this series, adjuvant treatment of localized ESSs was associated with the absence of recurrence.

Targeted agents in metastatic Xp11 translocation/TFE3 gene fusion renal cell carcinoma (RCC): a report from the Juvenile RCC Network.

BACKGROUND: Xp11 translocation renal cell carcinoma (RCC) is an RCC subtype affecting 15% of RCC patients <45 years. We analyzed the benefit of targeted therapy [vascular endothelial growth factor receptor (VEGFR)-targeted agents and/or mammalian target of rapamycin (mTOR) inhibitors] in these patients. PATIENTS AND METHODS: Patients with Xp11 translocation/TFE3 fusion gene metastatic RCC who had received targeted therapy were identified. Nuclear TFE3 positivity was confirmed by reviewing pathology slides. Responses according to RECIST criteria, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Overall, 53 patients were identified; 23 had metastatic disease, and of these 21 had received targeted therapy (median age 34 years). Seven patients achieved an objective response. In first line, median PFS was 8.2 months [95% confidence interval (CI) 2.6-14.7 months] for sunitinib (n = 11) versus 2 months (95% CI 0.8-3.3 months) for cytokines (n = 9) (log-rank P = 0.003). Results for further treatment (second, third, or fourth line) were as follows: all three patients receiving sunitinib had a partial response (median PFS 11 months). Seven of eight patients receiving sorafenib had stable disease (median PFS 6 months). One patient receiving mTOR inhibitors had a partial response and six patients had stable disease. Median OS was 27 months with a 19 months median follow-up. CONCLUSION: In Xp11 translocation RCC, targeted therapy achieved objective responses and prolonged PFS similar to those reported for clear-cell RCC.

[Molecular targeted therapies in small-cell lung cancer]. / Thérapies moléculaires ciblées dans le cancer du poumon à petites cellules.

Small-cell lung cancers (SCLC) are aggressive malignancies, however, characterized by high primary chemosensitivity. Unfortunately, for the vast majority of patients, relapse is the rule with emergence of secondary resistance mechanisms. In the era of molecular targeted therapies, characterization of a number of molecular abnormalities has encouraged implementation of several clinical trials. This literature review summarizes the various pharmacological approaches used in SCLC to improve survival in localized and extensive forms of the disease. Initial trials with molecular targeted therapies have not been able to improve clinical outcome compared to the standard etoposide-cisplatin chemotherapy regimen in extensive forms. However, new targets continue to be identified and many treatments are currently being assessed, including blockade of angiogenesis, signal transduction, cell cycle or induction of apoptosis.