Importance: Surgical treatment of patients with papillary thyroid cancer (PTC) by either lobectomy or total thyroidectomy (TT) has long been a topic of debate, especially for patients with intermediate-risk PTC.Objective: To compare recurrence-free survival (RFS) for patients with PTC and lymph node metastasis after lobectomy vs TT.Design, Setting, and Participants: This retrospective cohort study included a review of patients with PTC treated from January 1, 2000, to December 31, 2017. Propensity score matching (PSM) was performed between patients treated with lobectomy and TT. This study involved a single institute in a cancer referral center. Enrolled were adult patients (aged 18-75 years) with unilateral PTC and ipsilateral clinical lateral neck metastasis (cN1b). Patients with the following characteristics were excluded: a lymph node yield less than 20, primary tumor size greater than 4 cm, gross extrathyroidal extension, metastatic lymph node size greater than 3 cm, and distant metastasis. Data analysis was performed from April 1 to April 30, 2022.Exposures: Lobectomy and TT.Main Outcomes and Measures: The primary outcome was the association between extent of surgery and RFS, assessed using Cox proportional hazards regression models.Results: A total of 946 patients with PTC (mean [SD] age, 37.0 [12.1] years, 630 female individuals [66.6%]) were analyzed. Lobectomy (624 [66.0%]) was negatively correlated with the frequencies of older age (≥65 years, 17 [2.7%]), female sex (393 [63.0%]), multifocality (132 [21.2%]), minor extrathyroidal extension (259 [41.5%]), number of metastatic lymph nodes (median [range], 9 [6-14] nodes), and radioactive iodine ablation (0). After PSM with treatment period and potential prognostic factors (age, sex, primary tumor size, multifocality, minor extrathyroidal extension, number of lymph node metastases and lymph node ratio), 265 pairs of patients were available for analysis. After a median (range) follow-up of 60 (9-150) months in the lobectomy group and 58 (8-161) months in the TT group, 21 (7.9%) and 17 (6.4%) structural recurrences were identified in the lobectomy and TT groups, respectively. Lobectomy was not associated with significantly compromised 5-year RFS rate (lobectomy, 92.3% vs TT, 93.7%; adjusted hazard ratio, 1.10; 95% CI, 0.58-2.11; P = .77). Power analysis indicated that the test had 90% power to detect a more than 4.9% RFS difference. No significant difference in RFS was observed between patients treated with TT and radioactive iodine ablation (n = 75) and their counterparts (adjusted hazard ratio, 0.59; 95% CI, 0.14-2.41; P = .46).Conclusions and Relevance: Results of this cohort study suggest that patients with PTC and lymph node metastasis had a similar RFS after lobectomy vs those who had TT. If radioactive iodine ablation is not going to be performed, lobectomy may be an effective alternative option.

Medullary thyroid carcinoma (MTC) can only be cured through the excision of all metastatic lesions, but current clinical practice fails to localize the disease in 29% to 60% of patients. Previously, we developed a fibroblast activation protein inhibitor (FAPI)-based covalent targeted radioligand (CTR) for improved detection sensitivity and accuracy. In this first-in-class clinical trial, we head-to-head compared [68Ga]Ga-CTR-FAPI PET-CT and [18F]fluorodeoxyglucose ([18F]FDG) PET-CT in 50 patients with MTC. The primary endpoint was the patient-based detection rate, with [68Ga]Ga-CTR-FAPI exhibiting higher detection than [18F]FDG (98% vs. 66%, P = 0.0002). This improved detection was attributed to increased tumor uptake (maximum standardized uptake value = 11.71 ± 9.16 vs. 2.55 ± 1.73, P < 0.0001). Diagnostic accuracy, validated on lesions with gold-standard pathology, was greater for [68Ga]Ga-CTR-FAPI compared with [18F]FDG (96.7% vs. 43.3%, P < 0.0001). Notably, the management of 32% of patients was altered following [68Ga]Ga-CTR-FAPI PET-CT, and the surgical plan was changed for 66.7% of patients. Overall, [68Ga]Ga-CTR-FAPI PET-CT provided superior detection and diagnostic accuracy compared with [18F]FDG PET-CT, enabling precision management of patients with MTC. Significance: In this first-in-class clinical trial of CTR, [68Ga]Ga-CTR-FAPI demonstrated an improved patient-based detection rate (98%), tumor uptake (maximum standardized uptake value = 11.71 ± 9.16), and pathology-validated diagnostic accuracy (96.7%) compared with the currently approved method in MTC treatment. It directly altered management in 32% of patients, enabling precision diagnosis and management of MTC. See related commentary by Witney, p. 264

Radiotherapy has already been developed as the standard of care for patients with nasopharyngeal carcinoma (NPC), and precision staging, target volume delineation, prognosis prediction, and post-treatment surveillance are essential in the management of NPC. Positron emission tomography/computed tomography (PET/CT) is increasingly recognized as an imaging modality to guide precision radiotherapy in these areas. The feasibility and efficacy of ¹⁸F-FDG PET/CT have been confirmed in tumor diagnosis, treatment planning, prognosis, surveillance, and assessment. Coupled with the capability of revealing tumor metabolic information, ¹⁸F-FDG PET/CT is more accurate in identifying primary lesions and metastases of NPC than other conventional imaging methods including CT and MRI and shows the independently diagnostic and prognostic value for radiotherapy. However, ¹⁸F-FDG has limitations due to its physiological distribution in brain tissue and increasing uptake in post-radiation inflammation. Novel PET radiotracers including FAPI, NaF, CHO, and FLT are explored as alternatives with potential superiority for radiotherapy in NPC. In this review, we summarized the evolving role of PET/CT in the management of radiotherapy in NPC patients, aiming to facilitate precision radiotherapy from a molecular imaging aspect.

The National Comprehensive Cancer Network (NCCN) guidelines recommend completion thyroidectomy for patients with multifocal papillary thyroid carcinoma (PTC) diagnosed by paraffin pathology after lobectomy. However, studies for the influence of surgical range on prognosis of unilateral multifocal carcinoma are scarce. We analyzed the clinicopathological characteristics and long-term outcomes of patients with unilateral multifocal PTC to identify risk factors for recurrence and disease-related death. The clinical and pathological data of 123 cases with multifocal lesions in the unilateral thyroid lobe were retrospectively collected, including sex, age, stage, surgical range, histopathology characteristics, and follow-up data. The prognostic factors were analyzed by means of the Kaplan–Meier method. The recurrence in the contralateral residual thyroid was observed in 6 cases. The 10-year cumulative recurrence rate of the remnant thyroid was 7.0%. Extrathyroidal extension (ETE) was a significant prognostic factor, with χ2 equal to 4.043 and a P value of .044. One patient died from progression of pulmonary metastasis during the follow-up. The 10-year disease-specific survival rate was 96% and 14 cases experienced recurrences and underwent a second surgery (11.4%), and thus the 10-year recurrence-free survival rate was 83.2%. Multivariate analysis showed that the pathologic tumor (pT) stage was an independent prognostic factor for the recurrence-free survival rate (P <.0001, hazard ratio 2.871, 95% confidence interval 1.783–4.624). ETE is a significant prognostic factor for the recurrence of the remnant thyroid and pT stage is an independent prognostic factor for tumor recurrence-free survival. Lobectomy (with isthmectomy) is effective for most patients with unilateral multifocal PTC.

Objective: Distant metastasis in papillary thyroid microcarcinoma (PTMC) is rare but fatal, and its relationship with patient age remains unclear. The objective of this study was to examine the association between age at diagnosis and metachronous distant metastasis in PTMC.Methods: Consecutive patients who underwent thyroidectomy for PTC measuring 10 mm or less at a tertiary hospital from January 2000 to December 2016 were enrolled. Patients who had evidence of distant metastasis at diagnosis or underwent postoperative radioiodine (RAI) ablation were excluded. A Cox proportional hazards model with restricted cubic splines (RCS) was applied to examine the association between age at diagnosis and distant metastasis.Results: A total of 4,749 patients were evaluated. The median age was 44 years (range, 8–78 years), and 3,700 (78%) were female. After a median follow-up of 65 months, 21 distant metastases (20 lung, 1 liver) were recognized. A univariate Cox proportional model using a 5-knot RCS revealed a significant overall (p = 0.01) and a potential nonlinear association (p = 0.08) between distant metastasis and age at diagnosis. In multivariate analysis, age at diagnosis, extrathyroidal extension (ETE), and lymph node metastasis (pN+) were independent risk factors for distant metastasis. Compared with the middle-aged group (30–45 years old), younger and older patients had a higher risk of distant metastasis [HR, 95% CI, p-value, age ≤ 30, 4.54 (0.91–22.60), 0.06, age > 45, 6.36 (1.83–22.13), <0.01].Conclusion: Age at diagnosis is associated with metachronous distant metastasis of PTMC, and patients with younger or older age have a higher risk of distant metastasis than middle-aged patients.