Lung Metastases From Papillary Thyroid Cancer With Persistently Negative Thyroglobulin and Elevated Thyroglobulin Antibody Levels During Radioactive Iodine Treatment and Follow-Up: Long-Term Outcomes and Prognostic Indicators

Abstract

Background: The lung is the most frequent site of distant metastasis from differentiated thyroid cancer (DTC). However, lung metastasis from papillary thyroid cancer (PTC) with persistently negative thyroglobulin (Tg) and elevated Tg antibody (TgAb) levels is an extremely rare entity, and the prognosis is therefore elusive. We investigated the clinical characteristics, long-term outcomes, and prognostic factors of lung metastases in PTC patients with persistently negative thyroglobulin (Tg) and elevated Tg antibody (TgAb) levels during radioactive iodine (131 I) treatment and follow-up. Methods: We retrospectively reviewed 10,482 patients with DTC who underwent postoperative 131 I treatment from 2007 to 2017 at Shanghai Sixth's People's Hospital. The relationships between progression-free survival (PFS) and several variables were assessed by univariate and multivariate analyses using the Kaplan-Meier method and a Cox proportional hazards model, respectively. Results: Forty-seven patients with PTC were enrolled in this study (4.48‰ of all patients with DTC). The median age at the initial diagnosis of lung metastasis was 39.6 ± 15.4 years, and the patients comprised 14 male and 33 female patients (male: female ratio = 1.00:2.36). Twenty-five patients had 131 I avidity and 22 had non-131 I avidity. At the end of the 5-years follow-up, 12 patients exhibited progressive disease (PD), and 2 patients had died. At the end of the 10-years follow-up, 21 patients showed PD and five patients had died. The 5-and 10-year PFS rates were 74.47 and 53.32%, respectively; the 5-and 10-years overall survival (OS) rates were 95.74 and 89.36%, respectively. The timing of diagnosis of lung metastases, maximal size of lung metastases, and 131 I avidity were significantly associated with the 5-years PFS rate (P = 0.035, P = 0.030, and P<0.001, respectively). Only 131 I avidity was associated with the 10-years PFS rate (P < 0.001). The multivariate analyses also showed that non-131 I avidity were the independent poor prognostic factors for 10-years PFS at the end of follow-up (P < 0.001). Qiu et al. Lung Metastases From PTC With Elevated TgAb Conclusions: Lung metastases from PTC in patients with persistently negative Tg and elevated TgAb levels had an excellent prognosis and survival rate during 131 I treatment and follow-up. The loss of 131 I avidity remained the strongest independent predictor of a poor prognosis and survival in these patients.

Impact of lung metastases on overall survival in the phase 3 SELECT study of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer

“…The 5-year OS rates in patients whose average tumourvolume doubling time was 3e4 years and 1 year were 80% and 20%, respectively [7]. Another study demonstrated that the maximal size of lung metastases and timing of diagnosis of lung metastases were significantly associated with the 5-year PFS rate in patients with DTC who had lung metastases [8]. Of note, additional studies found that patients with lung-only metastases still have favourable survival outcomes compared to those with extrapulmonary metastases [9,10].…”

Survival prognostic factors for differentiated thyroid cancer patients with pulmonary metastases: A systematic review and meta-analysis

“…In the same line, the PFS was significantly better in the under-45 group than in the over-45 group (HR=3.85 [CI 1.29-11.47], P=0.02, N=306, Supplementary Figure 4 ) ( 20 , 26 ). However, there was no significant difference in PFS between the under and over 55 groups (HR=1.30 [CI 0.06-30.17], P = 0.87, N=136, Supplementary Figure 5 ) ( 24 , 38 ).…”

“…Three studies comprising 272 patients were included in the meta-analysis of ETE for PFS ( 15 , 20 , 38 ). Patients with ETE had significantly poorer PFS than those without ETE (HR=2.05 [CI 1.15-3.67], P=0.02, N=271, Figure 4D ).…”

Predictive Value of Clinical and Pathological Characteristics for Metastatic Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma: A 16-year Retrospective Study

“…There are still conflicts regarding the association between TgAb and DTC outcomes (19)(20)(21)(22)(23). Some previous studies suggested that a rising trend of TgAb itself could indicate cancer recurrence or persistence (19)(20)(21)(22). However, in another study (23), TgAb was not found to predict disease status in DTC patients.…”

“…In the current management guideline (3), the concept of using TgAb as DTC marker has not been taken into account with a full consensus. There are still conflicts regarding the association between TgAb and DTC outcomes (19)(20)(21)(22)(23). Some previous studies suggested that a rising trend of TgAb itself could indicate cancer recurrence or persistence (19)(20)(21)(22).…”