Background: MiT family translocation renal cell carcinoma (TRCC) is a rare and aggressive subgroup of renal cell carcinoma harboring high expression of c-MET. While TRCC response rates to VEGF receptor tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors are limited, efficacy of cabozantinib (a VEGFR, MET, and AXL inhibitor) in this subgroup is unclear. Methods: We performed a multicenter, retrospective, international cohort study of patients with TRCC treated with cabozantinib. The main objectives were to estimate response rate according to RECIST 1.1 and to analyze progression-free survival (PFS) and overall survival (OS). Results: Fifty-two patients with metastatic TRCC treated in the participating centers and evaluable for response were included. Median age at metastatic diagnosis was 40 years (IQR 28.5-53). Patients’ IMDC risk groups at diagnosis were favorable (9/52), intermediate (35/52), and poor (8/52). Eleven (21.2%) patients received cabozantinib as frontline therapy, 15 (28.8%) at second line, and 26 (50%) at third line and beyond. The proportion of patients who achieved an objective response was 17.3%, including 2 complete responses and 7 partial responses. For 26 (50%) patients, stable disease was the best response. With a median follow-up of 25.1 months (IQR 12.6-39), median PFS was 6.8 months (95%CI 4.6-16.3) and median OS was 18.3 months (95%CI 17.0-30.6). No difference of response was identified according to fusion transcript features. Conclusion: This real-world study provides evidence of the activity of cabozantinib in TRCC, with more durable responses than those observed historically with other VEGFR-TKIs or ICIs.

Pathological complete response (pCR) after neoadjuvant systemic treatment (NST) is an important prognostic factor in HER2-positive breast cancer. The majority of HER2-positive breast cancers are amplified at the HER2 gene locus, several genes are co-amplified with HER2, and a subset of them are co-expressed. The STARD3 gene belongs to the HER2 amplicon, and its role as a predictive marker was never addressed. The objective of this study was to investigate the predictive value of STARD3 protein expression on NST pathological response in HER2-positive breast cancer. In addition, we studied the prognostic value of this marker. Methods. We conducted a retrospective study between 2007 and 2020 on 112 patients with non-metastatic HER2-positive breast cancer treated by NST and then by surgery. We developed an immunohistochemistry assay for STARD3 expression and subcellular localization and determined a score for STARD3-positivity. As STARD3 is an endosomal protein, its expression was considered positive if the intracellular signal pattern was granular. Results: In this series, pCR was achieved in half of the patients. STARD3 was positive in 86.6% of cases and was significantly associated with pCR in univariate analysis (p = 0.013) and after adjustment on other known pathological parameters (p = 0.044). Performances on pCR prediction showed high sensitivity (96%) and negative predictive value (87%), while specificity was 23% and positive predictive value was 56%. Overall, specific, relapse-free, and distant metastasis-free survivals were similar among STARD3 positive and negative groups, independently of other prognosis factors. Conclusion: NST is an opportunity for HER2-positive cancers. In this series of over a hundred HER2-positive and non-metastatic patients, a STARD3-negative score was associated with the absence of pathological complete response. This study suggests that determining STARD3 overexpression status on initial biopsies of HER2-positive tumors is an added value for the management of a subset of patients with high probability of no pathological response.

Purpose. To assess the value of sentinel lymph node (SLN) sampling in high risk endometrial cancer according to the ESMO-ESGO-ESTRO classification. Methods. We performed a comprehensive search on PubMed for clinical trials evaluating SLN sampling in patients with high risk endometrial cancer: stage I endometrioid, grade 3, with at least 50% myometrial invasion, regardless of lymphovascular space invasion status; or stage II; or node-negative stage III endometrioid, no residual disease; or non-endometrioid (serous or clear cell or undifferentiated carcinoma, or carcinosarcoma). All patients underwent SLN sampling followed by pelvic with or without para-aortic lymphadenectomy. Results. We included 17 original studies concerning 1322 women. Mean detection rates were 89% for unilateral and 68% for bilateral. Pooled sensitivity was 88.5% (95%CI: 81.2–93.2%), negative predictive value was 96.0% (95%CI: 93.1–97.7%), and false negative rate was 11.5% (95%CI: 6.8; 18.8%). We noted heterogeneity in SLN techniques between studies, concerning the tracer and its detection, the injection site, the number of injections, and the surgical approach. Finally, we found a correlation between the number of patients included and the SLN sampling performances. Discussion. This meta-analysis estimated the SLN sampling performances in high risk endometrial cancer patients. Data from the literature show the feasibility, the safety, the limits, and the impact on surgical de-escalation of this technique. In conclusion, our study supports the hypothesis that SLN sampling could be a valuable technique to diagnose lymph node involvement for patients with high risk endometrial cancer in replacement of conventional lymphadenectomy. Consequently, randomized clinical trials are necessary to confirm this hypothesis.

Breast fibromatosis is a rare disease characterized by monoclonal fibroblast proliferation. It has no ability to metastasize but has a high local recurrence rate and often infiltrates surrounding tissues. Surgical treatment is the reference, but recently, new targeted therapies have emerged. We report an original case of a patient with breast fibromatosis who received exclusive medical treatment. Our aim was to analyze these treatments based on the clinical and radiological outcome, iatrogenic effects, and pharmacological action. We report the case of a 19-year-old woman who developed a desmoid-type fibromatosis of the lower inner quadrant of the right breast, measuring 50 × 25 mm (i.e., a volume of 27.4 cm3). Initial surgery was not possible because of potential esthetic and functional prejudice. Thus, she had an exclusive medical treatment including several lines: NSAIDs with tamoxifen and triptorelin, followed by sorafenib, then interferon α2b, and finally sunitinib. With tyrosine-kinase inhibitors (TKIs) (sunitinib), a significant partial response was observed (57% reduction of the maximal tumoral volume). For each treatment, we provided the clinical and radiological outcome in association with known pharmacological action. TKI had been an interesting alternative option to initial surgery, providing at least a partial response and potentially allowing less mutilating surgery. However, no pharmacological mechanism can unequivocally explain TKI efficacy. In general, breast fibromatosis should be treated along with oncologist and interventional radiologists in a trans-disciplinary modality, thus offering an adapted treatment for this particular desmoid-type fibromatosis localization.