Real-life patients with rDTC can benefit from lenvatinib treatment. AEs are frequent and should be closely monitored.

Objective: Gene alterations leading to activation of the MAPK pathway are of interest for targeted therapy in patients with advanced radioactive iodine refractory (RAI-R) thyroid carcinoma. Due to technical reasons gene fusion analysis in RNA isolated from formalin-fixed tumor tissues has till now been limited. The objective of the present study was to identify targetable gene rearrangements in RNA isolated from formalin-fixed RAI-R thyroid carcinomas. Design: Retrospective study in 132 patients with RAI-R thyroid carcinoma (59 papillary-, 24 follicular-, 35 Hürthle cell-and 14 anaplastic thyroid carcinoma). Methods: Total nucleic acid (undivided DNA and RNA) was isolated from formalin-fixed tissue. Extensive gene fusion analysis was performed in all samples that tested negative for pathogenic BRAF, NRAS, HRAS and KRAS variants. Results: Seven targetable gene fusions were identified in the remaining 60 samples without known DNA variants. This includes frequently reported gene fusions such as CCDC6/RET (PTC1), PRKAR1A/RET (PTC2) and ETV6/NTRK3 , and gene fusions that are less common in thyroid cancer (TPM3/NTRK1, EML4/ALK and EML4/NTRK3). Of note, most gene fusions were detected in papillary thyroid carcinoma and MAPK-associated alterations in Hürthle cell carcinomas are rare (2/35). Conclusion: Targetable gene fusions were found in 12% of RAI-R thyroid carcinoma without DNA variants and can be effectively identified in formalin-fixed tissue. These gene fusions might provide a preclinical rationale to include specific kinase inhibitors in the treatment regimen for these patients. The latter intends to restore iodine transport and/or take advantage of the direct effect on tumor cell vitality once progressive disease is seen.

BackgroundThe aims of this study were to report nutritional status in a large panel of patients with cancer requiring exclusive chemotherapy and to study the influence of nutritional status on their quality of life (QoL).MethodsThis work was a longitudinal cohort study performed at a French university teaching hospital. Eligible patients were individuals with a cancer needing treatment based on exclusive chemotherapy. Three work-ups were performed: i) before the administration of the first course of chemotherapy: T1, ii) before the administration of the second (for patients with 3 planned courses) or third (patients with 6 planned courses) course: T2, and iii) before the administration of the last planned course: T3. The following data were collected: general health (performance status) and nutritional status (weight, anorexia grading, albuminemia, pre-albuminemia, and C-reactive protein) and QoL.ResultsThe nutritional status of patients with cancer was preserved. Functional impairment, the presence of anorexia, the palliative nature of the chemotherapy, and an elevated C-reactive protein dosage were independent predictive factors of a lower QoL among patients assessed at the end of chemotherapy.ConclusionsAlthough larger studies should corroborate these findings, clinicians may include this information in the management of patients with cancer requiring exclusive chemotherapy to identify the most vulnerable patients.Trial registrationCurrent controlled trials NCT01687335 (registration date: October 6, 2011).Electronic supplementary materialThe online version of this article (doi:10.1186/s12955-017-0660-6) contains supplementary material, which is available to authorized users.

Background: Two-thirds of patients with metastatic differentiated thyroid cancer (DTC) become refractory to radioactive iodine (RAIR). The inhibition of the MAP-kinase pathway that is activated in case of BRAFV600E mutation might increase RAI incorporation into metastatic foci and reverse the RAI refractoriness. MERAIODE is a prospective multicentric open-label phase II trial, using a one-stage Fleming design, evaluating the efficacy and tolerance of trametinib (a MEK inhibitor) and dabrafenib (a BRAF inhibitor) treatment followed by the administration of RAI in metastatic RAIR DTC patients. Methods: Patients with BRAFV600E mutated RAIR metastatic DTC with RECIST progression within 18 months prior to enrollment and no lesion > 3 cm were included. A baseline rhTSH-stimulated diagnostic whole body scan (dc WBS) was performed prior to treatment initiation. Patients were treated with dabrafenib (150 mg bid) and trametinib (2 mg per day) for 42 days. At day 28, a second rhTSH-stimulated dc WBS was performed. After 35 days, a therapeutic activity of RAI (5.5 GBq) was administered. Primary endpoint was objective response rate (ORR) at 6 months according to RECIST v1.1 (central review). Patients: Among the 24 patients (mean age 67 years, 15 females) with a BRAFV600E mutated RAI refractory papillary DTC included between March 2018 and January 2020 in 8 French centers from the TUTHYREF netwok, 24 patients were treated and 21 patients were evaluable for the principal outcome at 6 months. Results: Abnormal RAI uptake was present in only 1 of the 21 patients (5%; 95%CI 0-24%) on a RAI diagnostic whole body scan (dc-WBS) performed prior to treatment initiation, in 11 patients, 11/17 (65%; 95%CI 38-86) on a dc-WBS performed 4 weeks after dabrafenib-trametinib initiation and in 20/21 (95%; 95%CI 76-100) on the post-therapeutic WBS performed after 5.5 GBq of RAI. The RECIST 6-months tumor response (central review) was partial response (PR) in 38% (95%CI 18-61), stable disease (SD) in 52% (95% CI 30-74) and progressive disease (PD) in 10% (95% CI 1-30). The median change in the sum of target lesions was -22% (range: -79 to +46) at 6 months after baseline. The 6-month fluorodesoxyglucose metabolic PET response was PR in 11/17 (65% 95%CI 38-86), SD in 4/17 (23%) (95% CI 7-50) and PD in 2/17 (12%; 95% CI 1-36). Among the 15 patients without Tg antibodies, 7 (47%) patients had a decrease of serum thyroglobulin level on T4 treatment by more than 50%All patients experienced at least one grade 1-2 adverse event, mainly asthenia, nausea, fever, diarrhea and cutaneous eruption. Nine grade 3 toxicities occurred in 6 treated patients. No grade 4-5 adverse event occurred Conclusion: The association of dabrafenib and trametinib in BRAFV600E mutated patients is effective for restoring RAI uptake and is followed by a tumor control in 90% of patients and by tumor response in 38% with limited adverse events. (PHRC 2015, NCT 03244956)