Prognostic role and characteristics of the indeterminate response in differentiated thyroid cancer: a systematic review.

PURPOSE: The management of differentiated thyroid cancer (DTC) is actually based on a dynamic risk stratification based on classes of response to the therapy. Indeterminate response (IR) includes a heterogeneous group of patients with different characteristics, particularly different Tg and AbTg levels and/or imaging findings. The aim of systematic review (SR) is to evaluate the prognosis, diagnostic findings and other characteristics of patients in the IR class. METHODS: A wide literature search in the Scopus, PubMed/MEDLINE and Web of Science databases was performed to find published articles on patients with DTC and IR after treatment. The quality assessment of studies was carried out using QUADAS-2 evaluation. RESULTS: Eight articles were included in the systematic review. Six studies evaluated the prognosis and the prognostic factor in patients with IR, one study evaluated the role of 2-[18F]FDG PET-CT in the management of patients with IR and biochemical incomplete response and one study the risk factors for IR. CONCLUSION: Patients with DTC and IR to therapy have a probability of disease relapse < 15%. Tg value could be a predictor of disease progression. The role of 2-[18F]FDG PET-CT needs to be further investigated.

Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapsed/refractory follicular lymphoma: a Fondazione Italiana Linfomi multicenter, randomized, phase III trial.

BACKGROUND: Optimal consolidation for young patilents with relapsed/refractory (R/R) follicular lymphoma (FL) remains uncertain in the rituximab era, with an unclear benefit of autologous stem cell transplantation (ASCT). The multicenter, randomized, phase III FLAZ12 (NCT01827605) trial compared anti-CD20 radioimmunotherapy (RIT) with ASCT as consolidation after chemoimmunotherapy, both followed by rituximab maintenance. PATIENTS AND METHODS: Patients (age 18-65 years) with R/R FL and without significant comorbidities were enrolled and treated with three courses of conventional, investigator-chosen chemoimmunotherapies. Those experiencing at least a partial response were randomized 1 : 1 to ASCT or RIT before CD34+ collection, and all received postconsolidation rituximab maintenance. Progression-free survival (PFS) was the primary endpoint. The target sample size was 210 (105/group). RESULTS: Between August 2012 and September 2019, of 164 screened patients, 159 were enrolled [median age 57 (interquartile range 49-62) years, 55% male, 57% stage IV, 20% bulky disease]. The study was closed prematurely because of low accrual. Data were analyzed on 8 June 2023, on an intention-to-treat basis, with a 77-month median follow-up from enrollment. Of the 141 patients (89%), 70 were randomized to ASCT and 71 to RIT. The estimated 3-year PFS in both groups was 62% (hazard ratio 1.11, 95% confidence interval 0.69-1.80, P = 0.6662). The 3-year overall survival also was similar between the two groups. Rates of grade ≥3 hematological toxicity were 94% with ASCT versus 46% with RIT (P < 0.001), and grade ≥3 neutropenia occurred in 94% versus 41%, respectively (P < 0.001). Second cancers occurred in nine patients after ASCT and three after radioimmunotherapy (P = 0.189). CONCLUSIONS: Even if prematurely discontinued, our study did not demonstrate the superiority of ASCT versus RIT. ASCT was more toxic and demanding for patients and health services. Both strategies yielded similar, favorable long-term outcomes, suggesting that consolidation programs milder than ASCT require further investigation in R/R FL.

High-sensitive basal serum thyroglobulin 6-12 months after thyroid ablation is strongly associated with early response to therapy and event-free survival in patients with low-to-intermediate risk differentiated thyroid carcinomas.

OBJECTIVE: High-sensitive thyroglobulin assays (hsTg) has decreased the need for stimulated Tg measurements in patients with differentiated thyroid carcinoma (DTC). However, multiple assays analyzing the same samples may report different values. Accordingly, appropriate assay-specific cut-off levels should be selected in representative patient series. Here, we evaluate the role of a new hsTg assay in low-to-intermediate risk DTC patients and select appropriate assay-specific clinical cut-off limits. DESIGN: This was a retrospective study. The response to treatment was assessed according to ATA. METHODS: Patients with low-to-intermediate risk DTC treated and regularly followed-up in our thyroid center. Tg was measured on the Kryptor Compact Plus Instrument (BRAHMS Thermo Fisher Scientific). RESULTS: The study series comprised 201 DTC patients and excellent response (ER) was demonstrated in 184 (91.5%). Optimized threshold of basal Tg (onT4-Tg) measured 6-12 months after initial treatment was set by ROC curves analysis at 0.28 ng/mL. Having onT4-Tg <0.28 ng/mL at 6-12 months after treatment was associated with longer disease-free survival of Kaplan-Meier (P < 0.001), ER at early follow-up (odds ratio (OR): 165, P < 0.001) and absence of relapse during follow-up (OR: 328, P = 0.0001). CONCLUSIONS: Patients with low- and intermediate-risk DTC could be considered cured when they have onT4-Tg levels <0.28 ng/mL coupled with negative imaging at their first post-ablation visit.