Renal cell carcinoma lung metastases treated by radiofrequency ablation integrated with systemic treatments: over 10 years of experience.

BACKGROUND: To determine safety and efficacy of radiofrequency ablation (RFA) for local treatment of lung metastases of renal cell carcinoma (RCC), sequenced or combined with systemic treatments. METHODS: Retrospectively, we studied 53 patients treated by RFA for a maximum of six lung metastases of RCC. The endpoints were local efficacy, overall (OS), disease-free (DFS), pulmonary progression-free (PPFS) and systemic treatment-free (STFS) survivals, complications graded by the CTCAE classification and factors associated with survivals. Potential factors analysed were: clinical and pathological data, tumoral staging of TNM classification, primary tumor histology, Fuhrman's grade, age, number and size of lung metastases and extra-pulmonary metastases pre-RFA. RESULTS: One hundred metastases were treated by RFA. Median follow-up time was 61 months (interquartile range 90-34). Five-year OS was 62% (95% confidence interval (CI): 44-75). Median DFS was 9.9 months (95% CI: 6-16). PPFS at 1 and 3 years was 58.9% (95%CI: 44.1-70.9) and 35.2% (95%CI: 21.6-49.1), respectively. We observed 3% major complications (grade 3 and 4 of CTCAE classification). Local efficacy was 91%. Median STFS was 28.3 months. Thirteen patients (25%) with lung recurrence could be treated by another RFA. T3/T4 tumors had significantly worse OS, PPFS and STFS. Having two or more lung metastases increased the risk of pulmonary progression more than threefold. CONCLUSION: Integrated to systemic treatment strategy, RFA is safe and effective for the treatment strategy of lung metastasis from RCC with good OS and long systemic treatment-free survival. RFA offers the possibility of repeat procedures, with low morbidity.

Adenosquamous Carcinoma of the Pancreas.

A 60-year-old woman presented to hospital with abdominal pain and massive weight loss. Imaging studies confirmed the presence of a tumor of the pancreas. Histologic analysis of the sampling performed by echoendoscopic ultrasound fine-needle aspiration found aspects evocative of adenosquamous carcinoma. This case report highlights the difficulties of clinical pathologic diagnosis for these occasionally composite tumors. The patient underwent palliative chemotherapy based on platinum and 5-fluorouracil, followed by second-line chemotherapy with FOLFIRI after progression. Adenosquamous carcinoma of the pancreas remains a rare tumor with very poor prognosis and limited therapeutic options.

Deciphering the complex role of thrombospondin-1 in glioblastoma development.

We undertook a systematic study focused on the matricellular protein Thrombospondin-1 (THBS1) to uncover molecular mechanisms underlying the role of THBS1 in glioblastoma (GBM) development. THBS1 was found to be increased with glioma grades. Mechanistically, we show that the TGFß canonical pathway transcriptionally regulates THBS1, through SMAD3 binding to the THBS1 gene promoter. THBS1 silencing inhibits tumour cell invasion and growth, alone and in combination with anti-angiogenic therapy. Specific inhibition of the THBS1/CD47 interaction using an antagonist peptide decreases cell invasion. This is confirmed by CD47 knock-down experiments. RNA sequencing of patient-derived xenograft tissue from laser capture micro-dissected peripheral and central tumour areas demonstrates that THBS1 is one of the gene with the highest connectivity at the tumour borders. All in all, these data show that TGFß1 induces THBS1 expression via Smad3 which contributes to the invasive behaviour during GBM expansion. Furthermore, tumour cell-bound CD47 is implicated in this process.

Traitement focal et traitement systémique dans la prise en charge du cancer du rein métastatique : une question de complémentarité.

FOCAL TREATMENT AND SYSTEMIC THERAPY IN METASTATIC KIDNEY CANCER: COMPLEMENTARY APPROACHES: To treat metastatic renal cell carcinoma, therapies used are with an oral intake, for the vast majority, and have many side effects that may compromise observance. Strategies of drug holiday have been studied and, in case of an indolent and oligometastatic tumor, studies have shown that active surveillance is possible to delay the introduction of systemic treatment, without compromising the patient survival. A multimodal approach combining systemic and focal treatments can be done with several objectives: to delay even more introduction of systemic treatment by focally treating metastases, to allow drug holiday after partial response to medical treatment by local control of persistent metastases, and to permit drug continuation even in case of dissociated response to systemic therapy, by focal treatment of metastasis(es) in progression. Technics that can be used for focal treatment are metastasectomy, radiofrequency ablation or cryotherapy, and stereotactic radiotherapy. In literature, studies that evaluated this approach are for almost retrospective studies, but they have reported interesting results in terms of local control and low morbidity. In the era of checkpoint's inhibitors, it seems important to make prospective collections of data to validate these practices. In any case, and because international recommendations about multimodal approach are poor, discussions between the different actors of the patient care are essential to find the most beneficial treatment for him.