BackgroundThe assessment of treatment response during neoadjuvant therapy for head and neck squamous cell carcinoma (HNSCC) relies largely on radiographic and endoscopic evaluations, which may fail to detect minimal residual disease (MRD). Circulating tumor DNA (ctDNA)-based MRD monitoring has emerged as a sensitive biomarker capable of revealing molecular disease activity that is not captured by imaging. Evidence supporting its use in the neoadjuvant setting of HNSCC remains limited.Case presentationWe report a 53-year-old man with locally advanced hypopharyngeal squamous cell carcinoma (cT4N2cM0) who received three cycles of neoadjuvant immunochemotherapy (toripalimab, cisplatin, and nab-paclitaxel). Radiologic and endoscopic assessment demonstrated a partial response with a 71.6% reduction in tumor burden and near-complete mucosal normalization. In contrast, ctDNA-MRD analysis showed elevated ctDNA levels compared with baseline, indicating molecular progression. Despite the favorable imaging response, the patient developed new distant metastases three months after definitive chemoradiotherapy and maintenance immunotherapy, confirming systemic disease progression.DiscussionThis case highlights the limitations of imaging in differentiating true tumor regression from residual disease during neoadjuvant therapy. Persistent ctDNA-MRD despite radiologic remission may signal occult progression and could influence critical treatment decisions, including the choice between surgery, chemoradiation, or systemic intensification. Accumulating evidence from other tumor types suggests that MRD clearance may predict pathological complete response (pCR), raising the possibility that accurate molecular assessment could help identify patients who may safely avoid surgery. However, MRD applications in neoadjuvant HNSCC—particularly hypopharyngeal carcinoma—remain sparsely studied.ConclusionctDNA-MRD may provide complementary and potentially earlier insights into treatment response compared with imaging alone. Its incorporation into neoadjuvant strategies for HNSCC warrants further investigation and may ultimately support more personalized and accurate therapeutic decision-making.

Tumor uptake stratified by CEA levels

Correlation between [68Ga]Ga-CTR-FAPI uptake and FAP expression

Tumor uptake stratified by newly diagnosed or persistent MTC

Patient-based and region-based detection rates

Representativeness of study participants

Detection rate of patients with calcitonin >2000 pg/ml

Tumor uptake stratified by calcitonin levels

Abstract Purpose: Medullary thyroid carcinoma (MTC) is curable only by complete resection of all malignant lesions; however, biochemical cure rates remain suboptimal because of imprecise lesion localization. We previously developed a covalent targeted radioligand fibroblast activation protein inhibitor (CTR-FAPI-30) with superior MTC detection rate and accuracy. This study evaluated whether [68Ga]Ga-CTR-FAPI-30 positron emission tomography–computed tomography (PET-CT)–guided surgery improves patient outcomes. Patients and Methods: In this prospective, open-label phase II clinical trial, 50 patients with MTC were enrolled and underwent [68Ga]Ga-CTR-FAPI-30 PET-CT–guided surgery. Patients were stratified into three predefined arms: (i) newly diagnosed MTC, R0 resection; (ii) recurrent MTC, R0 resection; and (iii) unresectable disease or distant metastasis. The primary endpoint was the biochemical cure rate at 1 month postoperatively. Secondary endpoints included event-free survival, the diagnostic accuracy of [68Ga]Ga-CTR-FAPI-30, and surgical plan modification rate. Results: The biochemical cure rates were favorable under [68Ga]Ga-CTR-FAPI-30–guided surgery, with 84.2% [95% confidence interval (CI), 60.4%–96.6%] in arm 1 (newly diagnosed, R0 resection) and 46.7% (95% CI, 21.3%–73.4%) in arm 2 (recurrent, R0 resection), both of which exceeded historical data (P = 0.007–0.049). For 231 lesions with gold-standard pathology, [68Ga]Ga-CTR-FAPI-30 demonstrated superior diagnostic accuracy (96.5% vs. 72.7%, P < 0.0001), sensitivity (98.5% vs. 81.7%, P < 0.0001), and specificity (85.3% vs. 20.6%, P < 0.0001) compared with conventional imaging. Surgical plans were modified in 46% of patients based on [68Ga]Ga-CTR-FAPI-30 PET-CT compared with investigator-determined approaches, with 91% of these modifications histopathologically justified. Conclusions: [68Ga]Ga-CTR-FAPI-30–guided surgery achieved favorable biochemical cure rates for both newly diagnosed MTC and recurrent MTC, enabling precision surgical resection through accurate lesion localization.

Objective:To explore the predictive value of blood routine parameters for surgical pathological complete response (PCR) following neoadjuvant immunotherapy combined with chemotherapy (NICC) in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC). Methods:We retrospectively analyzed patients with LAHNSCC who underwent NICC and the subsequent surgery at our hospital between May 2021 and November 2024. PCR included PCR of the primary tumor site (PPCR), PCR of the metastatic lymph node (LPCR), and PCR of both the primary tumor site and metastatic lymph node (PLPCR). Results:Of the 109 patients assessed, 41 (37.6%) achieved PPCR and 57 (52.3%) achieved LPCR. Of these, 29(26.6%) patients achieved PLPCR. LPCR did not exhibit any significant associations with the clinical parameters (p > 0.05). However, higher PPCR was significantly associated with the neutrophils-to-lymphocyte ratio (NLR) ≤ 2.115 (72.7% vs. 13.8%, odds ratio 18.672, 95% confidence interval 4.261-81.827, p < 0.001) Furthermore, patients with NLR ≤ 2.115 showed a significantly independent predictive factor for higher PLPCR (50.0% vs. 10.8%, p = 0.014). Conclusions:NLR may serve as valuable predictors of PCR following NICC in LAHNSCC. Specifically, patients with NLR ≤ 2.115 may have a higher likelihood of achieving PPCR and PLPCR.

Baseline characteristics of the enrolled patients

Incorporating a sulfur (VI)-fluoride exchange (SuFEx) chemistry-based linker, FAPI-based covalent targeted radioligand (CTR) showed better tumor binding affinity and longer retention time than FAPI-04 in animal studies. This study for the first time compared the lesion detection efficacy of [⁶⁸Ga]Ga-CTR-FAPI PET/CT and [⁶⁸Ga]Ga-FAPI-04 PET/CT in a radioiodine-refractory differentiated thyroid cancer clinical cohort. A single-center prospective comparative study was conducted, enrolling 40 RAIR-DTC patients with distant metastases. All patients underwent sequential [⁶⁸Ga]Ga-FAPI-04 PET/CT and [⁶⁸Ga]Ga-CTR-FAPI PET/CT examinations at a 24–48 h interval. Two experienced nuclear medicine physicians performed blinded visual analysis of the images to assess lesion detection status. Semi-quantitative analysis included the measurement of maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR) of lesions in different anatomical regions. The reference standard for lesion confirmation was a combination of conventional imaging, histopathological results (when feasible), and long-term clinico-radiological follow-up. The detection performances of the two imaging modalities were compared at the patient and lesion levels. Of the 40 enrolled patients, 37 had detectable metastatic lesions on both imaging modalities. Two patients had lesions exclusively detected by [⁶⁸Ga]Ga-CTR-FAPI PET/CT. [⁶⁸Ga]Ga-CTR-FAPI PET/CT achieved superior visual detection performance in 17.5

Detection rate of patients with calcitonin <500 pg/ml

This file contains Supplementary Tables 1-18, Supplementary Figure 1-2, clinical protocol and notification to attending physicians.

Detection rate of patients with calcitonin 500 to 2000 pg/ml

The literature has revealed considerable discrepancies in the nodal extension (ENE) definition and risk stratification. This study aimed to assess the extent of ENE in patients with lateral cervical lymph node metastases (pN1b) and evaluate its relationship with survival outcomes. A retrospective cohort analysis was conducted involving patients with pN1b PTC who underwent initial surgery between January 2000 and December 2018. Disease-specific survival (DSS) was analyzed using Kaplan–Meier survival curves, and compared using the log-rank test. The association between the extent of ENE and DSS was examined using Cox proportional hazards regression models. The study included 3,382 patients. Microscopic ENE (miENE) was identified in 808 patients (23.9

Background: Anaplastic thyroid carcinoma (ATC) is a rare and highly aggressive malignancy. Dabrafenib plus trametinib has shown efficacy in BRAFV600E-mutant ATC, but effective therapies remain limited for patients without this mutation. This study aimed to evaluate the efficacy and safety of anlotinib plus sintilimab in BRAFV600E-negative ATC.Methods: In this phase 2 trial, patients with BRAFV600E-negative unresectable or metastatic ATC received anlotinib (12 mg orally once daily on days 1-14 of a 21-day cycle) plus sintilimab (200 mg intravenously on day 1). The primary endpoint was investigator-assessed objective response rate (ORR). This study is registered at www.chictr.org.cn, ChiCTR2200067045.Results: From December 27, 2022, to June 11, 2025, 21 patients were enrolled. One (4.8%) patient achieved complete response, and nine (42.9%) patients achieved partial response. The ORR and disease control rate were 47.6% (10/21) and 85.7% (18/21), respectively. After median follow-up of 9.97 months (confidence interval [CI] 6.10 to NA), 61.9% (13/21) of patients had discontinued treatment, mainly due to disease progression (7/21, 33.3%), adverse events (AEs) (2/21, 9.5%), and other reasons (4/21, 19.0%). Median progression-free survival (PFS) was 9.63 months (CI 4.03 to NA), with eight (38.1%) patients were still on treatment. Subgroup analysis showed longer PFS in patients with neutrophil-lymphocyte ratio <3.06 (18.43 vs. 3.67 months; p = 0.010) and <5 (14.23 vs. 2.67 months; p = 0.002). Median overall survival was not reached (CI 13.90 to NA), 15 (71.4%) patients remained alive. AEs occurred in 66.7% (14/21) of patients, including grade 3 AEs in 19.0% (4/21). The most common were aspartate aminotransferase (AST) increased (6/21, 28.6%) and alanine aminotransferase (ALT) increased (5/21, 23.8%). Grade 3 immune-related AEs occurred in three patients, including AST/ALT increased, diarrhea, hypertension, and hypertriglyceridemia.Conclusions: Anlotinib plus sintilimab showed favorable efficacy and manageable safety in BRAFV600E-negative unresectable or metastatic ATC, supporting further investigation.

BACKGROUND:The right innominate interarteriovenous lymph nodes (RIAVLN) represent a distinct nodal group situated between the right innominate artery and vein. This area lies outside the conventional level VI-VII boundaries in thyroid carcinoma surgery and is seldom addressed in standard guidelines. Metastasis in this region is difficult to detect and surgically challenging due to its proximity to major vascular structures. This study aimed to analyze the clinical characteristics and surgical management of RIAVLN metastasis in patients with thyroid carcinoma. METHODS:We retrospectively reviewed 103 patients with thyroid carcinoma who underwent RIAVLN dissection between July 2017 and January 2024. All patients had preoperative contrast-enhanced CT scans suggesting nodal metastasis in this region. Demographic data, tumor subtype, surgical approach, and pathological findings were analyzed. The surgical technique emphasized cervical exposure of the carotid sheath, mobilization of the common carotid artery, and careful dissection of the interarteriovenous space, with partial sternotomy reserved for cases with severe adhesion or bleeding risk. RESULTS:The mean patient age was 39.9 ± 12.3 years (range, 18-68), with 42 males and 61 females. The cohort included 24 primary papillary, 63 recurrent papillary, 2 primary medullary, and 13 recurrent medullary thyroid carcinoma cases. Overall, 93 patients (90.3%) were successfully treated via a transcervical approach, while 10 (9.7%) required partial sternotomy. The mean number of RIAVLN dissected was 3.1 ± 2.9, and metastasis was confirmed in 77 patients (74.8%). The mean number of metastatic nodes among positive cases was 1.5 ± 2.4, with extranodal extension observed in 12 patients (11.7%). No major vascular injury or operative mortality occurred. CONCLUSIONS:RIAVLN metastasis is relatively common in recurrent thyroid carcinoma and represents an anatomically unique nodal group not covered by traditional classifications. In most cases, complete clearance can be safely achieved through a transcervical approach. Partial sternotomy should be reserved for patients with dense adhesions or high bleeding risk. Recognition of this region as a potential site of recurrence and mastery of its surgical anatomy are crucial for achieving optimal oncologic outcomes in thyroid cancer surgery.

Background: The 2025 American Thyroid Association (ATA) guidelines revised the recurrence risk stratification for papillary thyroid carcinoma (PTC), but did not incorporate patient age, a well-recognized prognostic factor. How age interacts with this modern stratification system remains unclear. To determine whether patient age modifies the association between the 2025 ATA risk stratification and recurrence risk in PTC. Methods: We conducted a retrospective cohort study of 14,397 patients with differentiated thyroid cancer who underwent initial thyroid surgery between 2000 and 2018. The primary outcome was structural recurrence-free survival. ATA2025 was categorized as low, low-intermediate, intermediate-high, and high risk. Age was modeled primarily as a continuous variable using restricted cubic splines. Cox proportional hazards models tested the interaction between ATA2025 and age, adjusted for sex and surgery-year period. Predicted 5-year structural recurrence risk was estimated by ATA2025 stratification and age. Model performance was assessed using Harrell’s C-index, time-dependent AUC, Brier score, calibration, decision curve analysis, bootstrap internal validation, temporal validation, and sensitivity analyses. Findings: Among 14,397 patients, median age was 43 years old, and median follow-up was 60 months. Structural recurrence occurred in 758 patients. ATA2025 showed clear prognostic separation: five-year structural recurrence risk increased from 1·7% in low-risk patients to 12·5% in high-risk patients. Age was significantly and nonlinearly associated with recurrence, and the ATA2025-by-age interaction was significant. Low and low-intermediate risk patients had low recurrence risk that generally decreased with age, whereas intermediate-high and high-risk patients showed U-shaped or J-shaped age-risk patterns, with risk decreasing toward middle age and rising again at older ages. In high-risk patients, predicted five-year recurrence risk increased from 9·1% at age 35 years to 20·1% at age 65 years. Adding age and the ATA2025-by-age interaction modestly improved prediction performance, with Harrell’s C-index increasing from 0·721 to 0·736 and five-year AUC from 0·724 to 0·741. Results were robust across internal validation, temporal validation, and sensitivity analyses. Interpretation: The 2025 ATA recurrence risk stratification effectively predicts structural recurrence in differentiated thyroid cancer, but age substantially recalibrates risk within ATA2025 stratification. Continuous, nonlinear age-specific risk estimation may improve individualized counselling and postoperative surveillance planning, particularly by distinguishing very low recurrence risk in older low-risk patients from rising recurrence risk in older high-risk patients.Funding This study was funded by National High Level Hospital Clinical Research Funding (grant number No. 2025-LYZX-Z-A08). The funding body had no role in the study design, data collection, analysis, interpretation of data or in writing the manuscript.