Toxicity and Tolerability of 177Lu-DOTA-TATE PRRT with a Modified Administered Activity Protocol in NETs of Variable Origin - A Phase 2 Registry Study.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) has been recently approved for advanced, metastatic, or progressive neuroendocrine tumors (NETs). OBJECTIVE: This study reports the adverse events (AEs) observed with patient-tailored administered activity. METHODS: Fifty-two PRRT naive patients were treated with 177Lu-DOTATATE. The administered activity ranges between 2.78 and 5.55 GBq/cycle using the patient's unique characteristics (age, symptoms, blood work, and biomarkers). RESULTS: The protocol was well tolerated with the overwhelming majority of participants being forty- six (88%), completing all 4 induction therapy cycles. The median cumulative administered activity was 19.6 GBq (ranged 3.8-22.3 GBq). A total of 42/52 (81%) reported at least one symptom, and 43/52 (83%) had evidence of biochemical abnormality at enrollment that would meet grade 1 or 2 criteria for AEs. These symptoms only slightly increase with treatment to 50/52 (96%) and 51/52 (98%), respectively. The most common symptoms were mild fatigue (62%), shortness of breath (50%), nausea (44%), abdominal pain (38%), and musculoskeletal pain (37%). The most common biomarker abnormalities were mild anemia (81%), reduced estimated glomerular filtration rate (eGFR) (58%), increased alkaline phosphatase (ALP) (50%), and leukopenia (37%). Of critical importance, no 177Lu-DOTATATE related grade 3 or 4 AEs were observed. CONCLUSION: Tailoring the administered activity of 177Lu-DOTATATE to the individual patient with a variety of NETs is both safe and well-tolerated. No patient developed severe grade 3 or 4 AEs. Most patients exhibit symptoms or biochemical abnormality before treatment and this only slightly worsens following induction therapy.

Performance of the American Thyroid Association Risk Classification in a Single Center Cohort of Pediatric Patients with Differentiated Thyroid Cancer: A Retrospective Study.

INTRODUCTION: Differentiated thyroid cancer (DTC) is the most common endocrine malignancy in children. Retrospective studies show conflicting results regarding predictors of persistent and recurrent disease after initial therapy. In 2015, the American Thyroid Association (ATA) proposed a clinical classification system to identify pediatric thyroid cancer patients at risk for persistent/recurrent disease. MATERIAL AND METHODS: We retrospectively included all patients in our registry diagnosed with papillary DTC at ≤ 18 years of age. We analyzed the prognostic performance of the ATA classification and other risk factors for predicting response to initial treatment and final outcome in pediatric DTC. RESULTS: We included 41 patients, 34 females and 7 males, diagnosed with papillary DTC at a mean (SD) age of 16.2 (1.8) years. Based on the ATA pediatric risk classification, patients were categorized as low (61%), intermediate (10%), or high risk (29%). The median follow-up period was 7.3 (1-41) years. After initial treatment, disease free status was achieved in 92%, 50%, and 42% of the low, intermediate, and high risk groups, respectively (P <0.01). At the last visit, persistent disease was present in 12%, 25%, and 33% (P=0.27). Assessing other risk factors, only the presence of distant metastases at diagnosis resulted in increased presence of persistent disease at last follow-up (P=0.03). CONCLUSION: This study supports the clinical relevance of the ATA risk classification for predicting the response to initial treatment. There was no clear prediction of long-term outcome, but this may be due to limited power caused by the small number of patients.