Donafenib in Progressive Locally Advanced or Metastatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Results of a Randomized, Multicenter Phase II Trial.

Background: An unmet need for more effective and affordable kinase inhibitors remains in patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) in China, where only sorafenib is approved for this indication. This study evaluated the 24-week objective response rate (ORR) to donafenib-a new, domestic multikinase inhibitor-in the treatment of locally advanced or metastatic RAIR-DTC in patients with measurable lesions. Two dose regimens (300 mg twice daily vs. 200 mg twice daily) were used to determine its optimal dosage and safety for further phase III studies. Methods: This study was a randomized, open-label, multicenter phase II trial. Thirty-five adult RAIR-DTC patients with at least one measurable targeted lesion according to RECIST 1.1 were enrolled from 12 centers in China and randomized to receive either 200 mg (17 patients) or 300 mg (18 patients) of donafenib orally twice daily for 24 weeks. The primary endpoint was ORR, and the secondary endpoints included progression-free survival (PFS) among others. Additionally, biochemical (serum thyroglobulin) and structural (total tumor diameter [TTD]) responses were assessed, change (ΔTTD) rates were calculated, and safety was evaluated. Results: The ORRs for the 200- and 300-mg arms were 12.5% and 13.33% (p = 1.000), respectively. The 300-mg arm had a nonsignificant, longer median PFS than the 200-mg arm (14.98 months vs. 9.44 months) (p = 0.351). There was a trend toward more tumor shrinkage in the 300-mg arm compared with the 200-mg arm (average ΔTTD rate -0.52 ± 0.71 vs. -0.04 ± 1.55 mm/month, p = 0.103). Most treatment-related adverse events (AEs) in both arms were grades 1-2. The most common grade 3 treatment-related AEs in both arms were palmar-plantar erythrodysesthesia and hypertension; the sum occurrence rates of these two AEs in the 200-mg and 300-mg arms were 11.43% and 22.86%, respectively. Conclusions: Donafenib was generally well tolerated. Both donafenib regimens demonstrated similar efficacy in terms of the ORR in locally advanced or metastatic RAIR-DTC. The results warrant further studies on donafenib as a new, feasible treatment option for RAIR-DTC patients. Clinical Trials.gov IDs: NCT02870569; CTR20160220.

Unusual synchronous skeletal muscle and lung metastasis in papillary thyroid cancer: A case report and review of the literature.

Papillary thyroid cancer (PTC) frequently metastasizes to the cervical lymph region and less often to the lung and bone. Metastasis to the skeletal muscles from PTC is extremely rare, especially concurrent lung and skeletal muscle metastases. The present study reports the case of a 31-year-old man with synchronous metastasis to the skeletal muscle and lung from PTC, six years following total thyroidectomy and consecutive 131Iodine treatments. Magnetic resonance imaging (MRI) revealed a 1.7×1.2×1.5 cm mass in the left gastrocnemius muscle, indicating a neurogenic tumor. The mass was subsequently resected and confirmed via histopathology to be metastatic PTC. We propose that, in the follow-up of patients with PTC, the measurable serum thyroglobulin level, whole body scan and other imaging modalities including MRI or positron emission tomography/computed tomography, must be closely monitored for potential distant metastases, particularly in cases of PTC with aggressive pathological behavior.

Analysis of 90 cases of antithyroid drug-induced severe hepatotoxicity over 13 years in China.

BACKGROUND: Antithyroid drug (ATD)-induced severe hepatotoxicity is a rare but serious complication of ATD therapy. The characteristics of severe hepatotoxicity have been reported in only a small number of patients. METHOD: Ninety patients with ATD-induced severe hepatotoxicity presenting during a 13 year period (2000-2013) who were about to undergo nuclear medicine therapy with (131)I from a sample of 8864 patients with hyperthyroidism were studied, and the outcomes were evaluated. RESULTS: The mean age of the patients with ATD-induced severe hepatotoxicity was 41.6±12.5 years (mean±standard deviation), and the female to male ratio was 2.2:1. The methimazole (MMI) dose given at the onset was 19.1±7.4 mg/day. The propylthiouracil (PTU) dose given at the onset was 212.8±105.0 mg/day. ATD-induced severe hepatotoxicity occurred in 63.3%, 75.6%, and 81.1% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. The types of severe hepatotoxicity did not differ significantly between the MMI and PTU groups (p=0.188). The frequency of the cholestatic type in the MMI group (35.3%, 18/51) was higher than that in the PTU group (17.9%, 7/39), but these frequencies were not significantly different (p=0.069). The patients who were treated with (131)I received an average dose of 279.1±86.1 MBq (n=84). Therapy was successful in 60 of the 67 patients (89.6%). The success rate was equivalent (p=0.696) between the groups receiving MMI (91.7%, 33/36) and PTU (87.1%, 27/31). CONCLUSIONS: Severe hepatotoxicity tends to occur within the first three months after the onset of ATD therapy. The type of ATD-induced severe hepatotoxicity did not differ between the MMI and PTU groups. (131)I therapy is an effective treatment approach for patients with ATD-induced severe hepatotoxicity.

Diagnostic performance of 18F-FDG-PET versus scintigraphy in patients with inflammatory bowel disease: a meta-analysis of prospective literature.

OBJECTIVE: The aim of this study was to evaluate the diagnostic performance of fluorine-18 fluorodeoxyglucose-PET (F-FDG-PET), leukocyte scintigraphy (LS), and monoclonal antigranulocyte antibody scintigraphy (MAAS) in patients with inflammatory bowel disease (IBD) and perform pairwise comparisons of the diagnostic accuracy between these different imaging modalities. METHODS: Through a search of PubMed, EMBASE, and the Cochrane Library (January 1993-May 2013), we performed a random effects meta-analysis and constructed summary receiver operating characteristic curves on per-bowel-segment or per-patient basis. Two-sample Z-tests were performed to evaluate differences in sensitivity, specificity, area under the curve (AUC), and the Q* index between any two diagnostic modalities on per-bowel-segment basis. RESULTS: Twenty prospective studies were reviewed. On per-bowel-segment basis, the F-FDG-PET had a pooled sensitivity of 0.84, specificity of 0.86, AUC of 0.913, and Q* index of 0.845, whereas for LS, the corresponding values were 0.79, 0.86, 0.877, and 0.808, respectively, and for MAAS they were 0.45, 0.94, 0.524, and 0.518, respectively. On per-patient basis, the corresponding values of LS were 0.91, 0.85, 0.937, and 0.874, respectively. Statistically significant differences were not found in the sensitivity, specificity, AUC, and Q* index between F-FDG-PET and LS on per-bowel-segment basis. CONCLUSION: F-FDG-PET has a high degree of diagnostic performance compared with LS and MAAS on per-bowel-segment basis in patients with IBD. LS may be used with satisfactory diagnostic accuracy in detecting active IBD when PET systems are unavailable. A larger prospective validation of these findings would be valuable.