Detection of BRAFV600E by digital PCR on fine-needle aspirate enables rapid initiation of dabrafenib and trametinib in unresectable anaplastic thyroid carcinoma.

Introduction: Recently, targeted therapies using BRAFV600E and MEK inhibitors (dabrafenib and trametinib, respectively) have been recommended in BRAF-mutated anaplastic thyroid carcinoma (ATC). Considering the fast development of ATC, droplet digital PCR (ddPCR) performed on fine-needle aspirate (FNA), which is a rapid, reliable, and low-cost method, appears interesting for the detection of BRAFV600E mutation in these patients and allows early initiation of targeted therapies. Results: In our two patients, both presenting extensive cervical masses inaccessible to surgery, ddPCR results were available in less than 24 h. Therefore, dabrafenib and trametinib were started only a few days after first contact. Conclusions: We suggest that ddPCR on FNA be used in non-resectable cervical masses for rapid BRAFV600E mutation detection in the hope that starting targeted therapies early might improve outcomes.

Complete resection of ulcerating, infiltrative, voluminous differentiated thyroid carcinoma.

An 87-year-old woman was referred to our department for a 15 cm right-sided cervical tumor with bleeding and skin ulceration, developed on a 6 cm papillary thyroid carcinoma diagnosed two years earlier. Surprisingly, there were no other compressive symptoms. Unexpectedly, but successfully, total thyroidectomy and neck dissection were performed. There were no poorly differentiated or anaplastic components in the final histological analysis. Impressive dehiscence occurred shortly after surgery and was also successfully managed. Our case highlights the benefit of considering surgery in the context of a tertiary care center even for an apparent massive aggressive cervical mass and despite old age.

Combination of Mitotane and Locoregional Treatments in Low-volume Metastatic Adrenocortical Carcinoma.

CONTEXT: European and French guidelines for ENSAT stage IV low tumor burden or indolent adrenocortical carcinoma (ACC) recommend a combination of mitotane and locoregional treatments (LRT) as first-line treatment. Nevertheless, the benefit of LRT in combination with mitotane has never been evaluated in this selected group of patients. OBJECTIVE: This work aimed to evaluate the therapeutic strategy of LRT combined with mitotane in patients with low tumor burden stage IVA ACC. METHODS: A retrospective chart review was performed from 2003 to 2018 of patients with stage IV ACC with 2 or fewer tumoral organs who received mitotane in our center. The primary end point was the delay between mitotane initiation and first systemic chemotherapy. Secondary end points were progression-free survival (PFS) and overall survival (OS) from mitotane initiation. Adjusted analyses were performed on the main prognostic factors. RESULTS: Out of 79 included patients, 48 (61%) patients were female and the median age at stage IVA diagnosis was 49.8 years (interquartile range [IQR], 38.8-60.0 years). Metastatic sites were mainly lungs (76%) and liver (48%). Fifty-eight (73%) patients received LRT including adrenal bed radiotherapy (14 patients, 18%), surgery (37 patients, 47%), and/or interventional radiology (35 patients, 44%). Median time between mitotane initiation and first chemotherapy administration was 9 months (IQR, 4-18 months). Median PFS1 (first tumor-progression) was 6.0 months (95% CI, 4.5-8.6). Median OS was 46 months (95% CI, 41-68). PFS1, PFS2, and OS were statistically longer in the mitotane plus LRT group compared to the mitotane-only group (hazard ratio [HR] = 0.39; 95% CI, 0.22-0.68; HR = 0.35; 95% CI, 0.20-0.63; and HR = 0.27; 95% CI, 0.14-0.50, respectively). Ten (13%) patients achieved complete response (CR), all from the mitotane plus LRT group. CONCLUSION: Our results endorse European and French guidelines for stage IV ACC with 2 or fewer tumor organs and favor the combination of mitotane and LRT as first-line treatment. For the first time, a significant number of CRs were observed. Prospective studies are expected to confirm these findings.