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Purpose: To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation. Patients and Methods: A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq–150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months. Results: Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3–4 AEs in 7 patients. Conclusions: Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.

Waterfall plot of the RECIST response

Swimmer plot of central RECIST response

Quality of Life scores

Purpose:To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation.Patients and Methods:A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq–150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months.Results:Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3–4 AEs in 7 patients.Conclusions:Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.

Tissue genotyping

Details of samples available for molecular analysis

Protocol inclusion and exclusion criteria

Radiological assessment

International audience; BACKGROUND: All randomised phase 3 studies of selective internal radiation therapy for advanced hepatocellular carcinoma published to date have reported negative results. However, these studies did not use personalised dosimetry. We aimed to compare the efficacy of a personalised versus standard dosimetry approach of selective internal radiation therapy with yttrium-90-loaded glass microspheres in patients with hepatocellular carcinoma.METHODS: DOSISPHERE-01 was a randomised, multicentre, open-label phase 2 trial done at four health-care centres in France. Patients were eligible if they were aged 18 years or older and had unresectable locally advanced hepatocellular carcinoma, at least one measurable lesion 7 cm or more in size, a hepatic reserve of at least 30% after selective internal radiation therapy, no extrahepatic spread (other than to the lymph nodes of the hilum, with a lesion 5% of patients) grade 3 or higher adverse events were ascites (one [3%] patient who received personalised dosimetry vs two [10%] patients who received standard dosimetry), hepatic failure (two [6%] vs none), lymphopenia (12 [34%] vs nine [43%]), increased aspartate aminotransferase concentrations (three [9%] vs two [10%]), increased alanine aminotransferase concentrations (three [9%] vs none), anaemia (two [6%] vs one [5%]), gastrointestinal haemorrhage (none vs two [10%]), and icterus (none vs two [10%]). One treatment-related death occurred in each group.INTERPRETATION: Compared with standard dosimetry, personalised dosimetry significantly improved the objective response rate in patients with locally advanced hepatocellular carcinoma. The results of this study suggest that personalised dosimetry is likely to improve outcomes in clinical practice and should be used in future trials of selective internal radiation therapy. FUNDING: Biocompatibles UK, a Boston Scientific Group company.

The most recent progress in the oncology field has led to a paradigm shift in the management of cancer with the tsunami of immune checkpoint inhibitors that are associated with a particular pattern of immunological adverse events. This is a case of a 54-year-old woman that demonstrated a granulomatous reaction in the same dermatomal distribution of a previously treated shingles infection during treatment with an anti-programmed death 1 agent (pembrolizumab) for a newly diagnosed stage IV Hodgkin lymphoma. The purpose of this case is to increase the awareness of oncologists dealing with a new pattern of side effects taking into account the patient’s background and recent exposures to latent viruses such as herpes zoster to prevent unnecessary diagnostic and therapeutic measures.

Simple Summary Total thyroidectomy used to be recommended for all thyroid cancers. We now know that some thyroid cancers have a relatively low risk of recurrence. Today, for some of these cancers, depending on the type of tumor, its’ size and other tumor characteristics, a thyroid lobectomy (or hemithyroidectomy) can be performed without increasing the patient’s risk of cancer recurrence. Thyroid lobectomy has the advantages of having less risk of surgical complications and a less frequent need for thyroid hormone replacement therapy. This approach is not optimal for all thyroid cancers, however, and careful tumor and patient selection are necessary. This review explains the rationale and criteria for patient selection for thyroid lobectomy for selected thyroid cancers. Abstract Many recent publications and guidelines have promoted a “more is less” approach in terms of treatment for low to intermediate risk differentiated thyroid cancer (DTC), which comprise the vast majority of thyroid cancers: less extensive surgery, less radioactive iodine, less or no thyroid hormone suppression, and less frequent or stringent follow-up. Following this approach, thyroid lobectomy has been proposed as a means of decreasing short- and long-term postoperative morbidity while maintaining an excellent prognosis for tumors meeting specific macroscopic and microscopic criteria. This article will examine the pros and cons of thyroid lobectomy for low to intermediate risk cancers and discuss, in detail, criteria for patient selection and oncological outcomes.

516 Background: 90Y loaded microsphere SIRT (radioembolization) is a treatment option in advanced HCC. However, no personalized dosimetric endpoints are currently used. The goal of this study was to compare the efficacy of 90Y loaded glass microsphere SIRT in HCC using a standard versus a personalized dosimetric approach. Methods: DOSISPHERE-01 was a multicenter, randomized phase 2 trial in unresectable HCC patients with at least one tumor ≥7cm. Treatment arm was randomly assigned (1:1) to standard dosimetry arm (SDA), with a goal to deliver 120±20Gy to the treated volume or to personalized dosimetry arm (PDA) with a goal to deliver at least 205Gy to the index lesion. The primary endpoint was the response rate (RR) of the index lesion according to EASL criteria. Secondary endpoints included dose response evaluation, safety and overall survival (OS). Results: Sixty HCC patients were randomized (PDA 31, SDA 29, intent to treat population-ITTP-), and 56 treated (28 in each arm). RR was significantly increased in the PDA versus the SDA, in the ITTP, respectively 64.5% versus 31% (p=0.0095) as in the safety population -SP- (treatment effectively received, personalized 35, standard 21), respectively 74.3% versus 14.3% (p

Myeloid sarcoma (MS) is defined as a tumor mass consisting of myeloid blasts with or without maturation occurring at an anatomical site other than bone marrow (BM). MS may occur before, concurrently or after a characterized acute myeloid leukemia (AML). Cytogenetic abnormalities are found in 50% of the cases but molecular alterations are less well described and involved FLT3 and/or NPM1 mutations. Mutations in IDH1 and IDH2 genes are found in 15% to 20% of patients with AML but have never been described in MS. Mutated IDH enzymes produce in vast excess D-2-hydroxyglutarate (2-HG) in leukemic cells, which can act as a biomarker predictive of the presence of IDH1 and IDH2 mutations. As availability of DNA sequencing techniques on paraffin samples are limited, molecular characterization of MS remained difficult. We asked whether in MS, serum 2-HG would predict the presence of IDH1/2 mutations at diagnosis, and could provide a biomarker for follow up. Tissue samples and serum samples from 8 patients with a MS diagnosis were analyzed. High quality genomic DNA was extracted from frozen MS samples using conventional phenol/chloroforme extraction procedures. Exon 4 of IDH1 and IDH2 genes (IDH1/R132 and IDH2/R140 and /R172 codons) was amplified by PCR using HotStar Taq polymeraze (Qiagen) and primers. Direct sequencing was performed using the Sanger method as previously described. In case of MS relapse or AML evolution, IDH1 and IDH2 genes were analyzed in the same way from frozen tissue sample or bone marrow sample. Serum samples at MS diagnosis were analyzed for total 2-HG, D-2-HG and L-2-HG by reverse-phase liquid chromatography coupled to mass spectrometry. In case of myeloid sarcoma with IDH1/2 mutation, 2-HG values were compared to 18F-FDG-PET results when available during remission phase and at relapse. Three patients (3/8; 37.5%) had an IDH2 R140Q mutation at diagnosis of MS localized to lymph node, soft tissue, skin or pharynx. At MS diagnosis, serum total 2-HG, D-2-HG and ratio D/L-2-HG were significantly higher in case of myeloid sarcoma with IDH2 R140Q mutation compared to patients with no IDH mutation (Table 1). Serum total 2-HG level ≥2µM or D-2-HG level ≥1.8µM or ratio D/L 2-HG >2.5 were significantly associated with the presence of IDH2 mutation (Fisher's exact test P≤0.02). Table 1. Myeloid sarcoma with IDH2 R140Q mutation (N=3) Myeloid sarcoma without IDH2 R140Q mutation (N=5) Median total 2-HG (µM) 4.1 (range: 3.1-30.1) 1.4 (range: 1-1.6) Median D-2-HG (µM) 3.7 (range: 2.3-28) 0.6 (range: 0.5-0.8) Median L-2-HG (µM) 0.8 (range: 0.4-2.1) 0.8 (range: 0.4-0.8) Median ratio D/L 2-HG 8.3 (range: 2.9-18.8) 1 (range: 0.7-1.7) All 3 patients with IDH2 R140Q mutated MS received intensive chemotherapy treatment and achieved complete remission (CR). Two patients relapsed: one experienced isolated extramedullary relapse (thigh muscle); one had a bone marrow relapse. IDH2 R140Q mutation was found at the site of relapse in both cases. When available, serum 2-HG values and 18F-fluorodeoxyglucose-positron-emission tomography (FDG-PET) were compared at different time points (at diagnosis, remission and relapse; Table 2). Table 2. Patient #1 Patient #2 Patient #3 FDG-PET at diagnosis (SUVmax) - 17 5.25 Serum 2-HG at diagnosis (µM) 4.1 3.1 30.1 FDG-PET in remission (SUVmax) 0 - 9.6 (N=4) 0 (N=4) - Serum 2-HG in remission (µM) 0.5 - 1.1 (N=4) 0.6 - 3.1 (N=4) 3.4 - 17.9 (N=3) FDG-PET at MS relapse/evolution to AML (SUVmax) 6.1 - 0 Serum 2-HG at MS relapse/evolution to AML (µM) 2.3 - 16.7 Time between diagnosis and MS relapse/evolution to AML (months) 30 - 9 Serum 2-HG values were in accordance with FDG-PET interpretations except in patient #1 who presented a transient hypermetabolic splenic nodule (SUVmax 9.6) without serum 2-HG increase. Patient #2 remained in CR but had recently increased 2-HG values without overt relapse. Patient #3 presented relapse as a refractory anemia with excess of blast without extra-medullary localization. FDG-PET didn't find any abnormality contrary to the persistent increased value of serum 2-HG (total 2-HG: 16.7µM). These data show that myeloid sarcoma can be associated with IDH2 R140Q mutation and suggest that 2-HG measurement in the serum predicts the presence of IDH1/2 mutations at diagnosis. During follow-up, serum 2-HG values could be representative of the disease status. Because of IDH inhibitors promising results in AML, 2-HG screening at MS diagnosis could be useful. Disclosures Ribrag: Celgene: Research Funding; Esai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmamar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. De Botton:Agios pharmaceuticals: Research Funding.