Modified dynamic risk stratification system further predicts individual outcome in patients with intermediate-risk papillary thyroid cancer.

OBJECTIVE: We assessed the contribution of initial treatment response to further refining prediction of individual outcomes in intermediate-risk papillary thyroid cancer (PTC) on the American Thyroid Association (ATA) risk stratification system. Dynamic risk stratification (DRS) as originally proposed by Tuttle et al. in 2010 was modified to also include serum antithyroglobulin antibodies (TgAb) as a surrogate marker of the likelihood of persistent disease, specifically in patients with thyroglobulin assay interference by TgAb. METHODS: Three hundred and seventy-three patients with ATA intermediate-risk PTC were enrolled retrospectively upon reviewing medical records. Patients were followed at the National Cancer Institute in Bogota, Colombia after being treated with total thyroidectomy and I-131 therapy between 2009 and 2013. Best response to initial therapy was classified as excellent, indeterminate, biochemically incomplete or structurally incomplete. Final disease status after a median follow-up of 7.1 years was classified as no evidence of disease (NED), indeterminate, or persistent disease (either biochemically or structurally). The rate of recurrence was determined in excellent responders. RESULTS: Excellent response was achieved by 164 patients (43.9%). At a median follow-up of 42 months, 19 (11.6%) had experienced recurrence. 87.4% of initially excellent responders available at the final checkpoint were NED, compared to 28% of those with biochemically or structurally incomplete response and to 60.2% of all ATA intermediate-risk PTC patients in our cohort. CONCLUSIONS: Modified DRS further predicted individual outcomes in intermediate-risk PTC, potentially allowing ongoing management to be tailored accordingly.

Eficacia de lutecio-177 DOTATATE/TOC en pacientes con tumores neuroendocrinos bien diferenciados en estado avanzado. Ensayo clínico fase II / Efficacy of Lutetium-177 DOTATATE/TOC in Advanced Neuroendocrine Tumors

Resumen Introducción: En 2009, el Instituto Nacional de Cancerología (INC) elaboró el 177Lu-DOTATATE/TOC. El propósito del estudio fue demostrar la eficacia de estos radiopéptidos en el tratamiento paliativo de pacientes con tumores neuroendocrinos (TNE) avanzados inoperables (metastásicos o localmente avanzados) y en progresión. Métodos: Ensayo clínico abierto fase II de un solo brazo en 13 pacientes adultos con TNE grado 1 o 2, con expresión de receptores de somatostatina en lesiones blanco demostrada por captación Krenning 3 o 4 en 99mTc-HYNIC TOC. Los pacientes fueron tratados con 177Lu-DOTATATE o 177Lu-DOTATOC (según disponibilidad) a una actividad acumulativa proyectada de 600-800 mCi dividida en 3-4 dosis cada 6-9 semanas comenzando siempre con una actividad fija de 200 mCi y dosimetría con la primera dosis. El desenlace primario fue la respuesta objetiva calculada 6 y 12 meses después de la última dosis del tratamiento. Resultados: Se incluyeron 13 pacientes (7 mujeres) de 63 ± 11,6 años con TNE avanzado inoperable y en progresión. La actividad final administrada fue de 800 mCi, 600 mCi, 400 mCi y 200 mCi en 4, 7, 1 y 1 pacientes, respectivamente. La tasa de control de enfermedad a 6 y 12 meses fue de 69,2% y 45,5%, respectivamente, logrando únicamente enfermedad estable. Fallecieron 7 pacientes, 2 de ellos en los primeros 6 meses. La mediana de supervivencia global a partir de la última dosis del radiopéptido fue de 15,7 meses. Conclusiones: Se corroboró la eficacia y la seguridad del tratamiento con los radiopéptidos en NETs avanzados.

Abstract Objectives: The National Cancer Institute first elaborated 177Lu-DOTATATE/TOC in 2009. The purpose of this study was to prove the efficacy of these radiopeptides in the palliative treatment of patients with progressive advanced inoperable neuroendocrine tumors (NETs). Methods: A single-phase phase II open clinical trial was conducted in 13 adult patients with grade 1 y 2 NETs, with expression of somatostatin receptors in target lesions proven by Krenning Score 3 or 4 uptake in 99mTc-HYNIC TOC. Patients were treated with 177Lu-DOTATATE or 177Lu-DOTATOC (depending upon availability) at a projected acumulative activitiy of 600-800 mCi divided into 3-4 doses every 6-9 weeks always beginning with a fixed activity of 200 mCi and dosimetry during the first dose. The primary outcome was objective response to therapy. Results: 13 patients (7 women) aged 63 ± 11.6 years with inoperable advanced NETs were included. The final therapeutic administered activity was 800 mCi, 600 mCi, 400 mCi and 200 mCi in 4, 7, 1 and 1 patients, respectively. The disease control rate at 6 and 12 months was 69.2% and 45.5%, respectively, only obtaining stable disease. Six patients died, 2 of them in the first 6 months. Median overall survival was 15.7 months from the last treatment dose. Conclusions: The efficacy of the treatment with 177Lu-DOTATATE or 177Lu-DOTATOC radiopeptides elaborated in-house was confirmed, becoming a management alternative for patients with advanced NETs.

Intermediate-Risk Papillary Thyroid Cancer: Risk Factors for Early Recurrence in Patients with Excellent Response to Initial Therapy.

BACKGROUND: Patients with excellent response to initial therapy have a low rate of tumor recurrence. The objectives of this study were to evaluate the rate of early tumor recurrence in patients with intermediate-risk papillary thyroid cancer who had an excellent response to initial treatment and to identify risk factors. METHODS: This retrospective cohort study included 217 patients with American Thyroid Association intermediate-risk papillary thyroid cancer who had a documented excellent response to initial treatment (total thyroidectomy and adjuvant therapy with 100-150 mCi [3.7-5.5 GBq] of radioactive iodine [RAI]). The assessed outcome was recurrence, defined as new evidence of disease after any disease-free period. Multivariate logistic regression and Cox regression models were used to determine the factors associated with recurrence upon recording clinical, surgical, and pathology variables. RESULTS: Sixteen (7.4%) cases of recurrent disease were documented after a median follow-up period of 42 months (range 17-88 months). Structural recurrence was documented in 10 (62.5%) patients, and biochemical recurrence was documented in the remaining six patients. The logistic regression model identified a significant association between early recurrence and pN1b involvement (odds ratio [OR] = 10.81 [confidence interval (CI) 1.87-62.59]), lateral neck RAI uptake (OR = 6.06 [CI 1.67-22]), and pre-ablation thyroglobulin >10 ng/mL (OR = 4.01 [CI 1.16-13.85]). Variables that proved significant in the Cox regression model were: pN1b involvement (hazard ratio = 9.6 [CI 1.91-48.52]) and lateral neck RAI uptake (hazard ratio = 5.95 [CI 1.86-18.97]). CONCLUSION: The observed early recurrence rate of 7.4% is uncharacteristically high for a population of patients who had an excellent response to initial treatment. The significant association that was found between recurrent disease and lateral neck lymph node metastasis, lateral neck I131 uptake in post-therapy whole-body scan, and pre-ablation thyroglobulin levels >10 ng/mL indicates that early recurrence (<5 years) most likely indicates progression of micrometastatic disease already present at diagnosis and unsuccessfully eradicated with initial therapy.