Aug 2026· JAMA Otolaryngology - Head and Neck Surgery· 0 citations· 28 references
Medicine
TL;DR
The findings of this cohort study suggest that the high prevalence of TERT promoter variants in older patients largely explains the association between age and worse prognosis in PTC.
Abstract
Importance
Older age at diagnosis is associated with worse outcomes in papillary thyroid carcinoma (PTC). The current American Joint Committee on Cancer tumor-node-metastasis staging system incorporates an age of 55 years or older as staging criteria. TERT promoter variants are also associated with aggressive disease.
Objective
To evaluate the interplay between age, TERT promoter variants, and survival outcomes in PTC.
Design, Setting, and Participants
This multi-institutional retrospective cohort study was conducted from 1993 to 2020 at 3 academic centers in the US, with integration of publicly available cohorts from The Cancer Genome Atlas (TCGA) and American Association of Cancer Research's Project Genomics Evidence Neoplasia Information Exchange (AACR GENIE). The cohort included 169 patients with PTC from 3 US academic centers, who were integrated with TCGA and AACR GENIE, yielding a combined analytic population of 1555 patients with PTC. The association between age and TERT was examined across all patients. Within the multi-institutional cohort with long-term follow-up (n = 169), the association between TERT and survival was further examined.
Exposures
Age at diagnosis and TERT promoter status.
Main Outcomes and Measures
The primary outcome was disease-specific survival (DSS), and the secondary outcome was progression-free survival (PFS).
Results
Across all cohorts (N = 1555; 966 female individuals [62.1%] and 589 male individuals [37.9%]), the prevalence of TERT promoter variants increased progressively with age (r = 0.59; 95% CI, 0.54-0.63), being rare in patients younger than 30 years (<2%) and reaching 32% to 70% in those older than 65 years. For survival analyses, 169 patients were included (median follow-up, 13.7 years; 95% CI, 10.4-15.9 years). Among patients younger than 55 years without a TERT promoter variant, 10-year DSS was 100% and 10-year PFS was 83%. Among those 55 years or older, 10-year DSS was 91% for TERT wild-type tumors and 51% for TERT-variant tumors (91% vs 51%, respectively; difference, 40%; 95% CI, 4-68). A similar trend was observed for PFS (10-year PFS of 75% for TERT wild-type vs 23% for TERT variant; difference, 52%; 95% CI, 9-82). In multivariable analysis, TERT promoter variants remained independently associated with worse DSS after adjustment for age and pathologic tumor, node, and metastasis categories.
Conclusions and Relevance
The findings of this cohort study suggest that the high prevalence of TERT promoter variants in older patients largely explains the association between age and worse prognosis in PTC. TERT promoter status offers more biologically grounded prognostic information than age and may improve risk stratification.
Background: Renal cell carcinoma (RCC) is a heterogeneous malignancy arising from renal tubular epithelium
and accounts for 2–3% of adult cancers. Although RCC predominantly affects older individuals, its incidence in
younger patients has shown a rising trend. Young-onset RCC may differ from conventional RCC in terms of tumor
biology, genetic profile, and clinical outcomes, making its evaluation clinically significant.
Aim: The present study aimed to evaluate the genetic patterns in young-onset RCC patients (≤46 years) and to
correlate these findings with tumor characteristics, histopathological subtypes, recurrence, and survival outcomes.
Methodology: This retrospective and prospective observational study was conducted at a tertiary care center
between 2013 and 2024. A total of 34 young RCC patients meeting inclusion criteria were analyzed. Clinical,
demographic, radiological, histopathological, and treatment-related data were collected. Genetic testing using
Next-Generation Sequencing (NGS) with Whole Exome Sequencing (WES) was performed in selected high-risk
patients after genetic counseling. Statistical analysis was carried out using SPSS version 25.0.
Results: The mean age of patients was 38.2 ± 5.6 years, with male predominance. Clear cell RCC was the most
common histological subtype. Most tumors were detected incidentally and presented at an early stage with low
histological grade. Pathogenic or likely pathogenic germline variants were detected in a minority of patients,
predominantly involving the VHL gene. Recurrence was observed mainly in patients with advanced tumor stage
and lymph node involvement. Overall survival outcomes were favorable in early-stage disease.
Conclusion: Young-onset RCC is characterized by early-stage presentation, favorable histopathology, low
recurrence rates, and improved survival. While RCC-specific germline mutations are uncommon, selective genetic
evaluation remains valuable in high-risk patients
K. Narayanasamy, Vaibhav Thakare, M. P. Kumar et al.· International Journal of Pha...· 0 citations
BackgroundAdvanced follicular thyroid carcinoma (FTC) represents a clinically heterogeneous subgroup of differentiated thyroid cancer with variable long-term outcomes. We aimed to develop and internally validate a population-based nomogram for predicting 3-, 5-, and 10-year disease-specific survival (DSS) in patients with stage III-IV FTC using SEER registry data.Materials and MethodsThis retrospective cohort study utilized data from the SEER 17 registry (2010-2022). A total of 1027 patients with stage III-IV FTC were included and randomly assigned to training (n = 718) and validation (n = 309) cohorts. Clinical and demographic variables were analyzed. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify independent prognostic factors. A nomogram was constructed based on the final multivariable model. Predictive performance was assessed using ROC and calibration analyses.ResultsThe mean age of the cohort was 63.5 years (±11.7), and 59.3% of patients were female. Multivariable analysis identified age, stage IV disease, N1 nodal status, unmarried status, and surgical treatment category as independent predictors of DSS. The nomogram demonstrated strong discriminative performance, with AUC values of 0.953, 0.966, and 0.903 for predicting 3-, 5-, and 10-year DSS, respectively. Calibration analyses showed acceptable agreement.ConclusionThis nomogram provides a population-level estimate of DSS in advanced FTC. While the model may support preliminary risk stratification using readily available registry variables, its clinical interpretation should consider the absence of key biologic and treatment-response factors not captured in SEER, including vascular invasion, molecular alterations, and systemic therapy data.
A. Şanlı, Isa Karaca, Bilal Turan et al.· The American surgeon· 0 citations
BACKGROUND
How metastatic nodal burden influences the prognosis of school-age children and adolescents (SACAs) with papillary thyroid cancer (PTC) remains unclear. We investigated the independent impact of numerical metastatic nodal burden on clinical outcomes in these patients.
MATERIALS AND METHODS
This multicenter retrospective cohort study included SACAs with PTC aged 18 years and older who had undergone total thyroidectomy and radioiodine therapy across 12 nuclear medicine departments in China. Persistent biochemical and structural diseases were evaluated. The independent role of metastatic nodes in persistent disease was evaluated using Cox proportional hazards regression.
RESULTS
In total, 486 SACAs with PTC were analyzed, of whom 115 had N1a and 371 had N1b. Among SACAs with N1b PTC, a higher number of metastatic lymph nodes, analyzed as a continuous variable, was identified as an independent risk factor for persistent structural disease (HR: 1.06; 95% CI: 1.01-1.11). When analyzed as a categorical variable, patients in the third (16-22 nodes) and fourth (>22 nodes) quartiles of the number of metastatic nodes exhibited an increased hazard of persistent structural disease (HR: 3.35; 95% CI: 1.13-9.97; P=0.029 and HR: 5.52; 95% CI: 1.59-19.13; P=0.007, respectively). ROC analysis identified a cutoff of ≥14 metastatic lymph nodes for predicting persistent structural diseases. However, for SACAs with N1a PTC, analysis of the number of metastatic nodes revealed no association with persistent disease.
CONCLUSIONS
The number of metastatic nodes is a predominant factor associated with persistent disease, and incorporating quantitative assessment of metastatic nodes may improve risk stratification in SACAs with N1b PTC.
Liu Xiao, Wei Chang, H. Feng et al.· Clinical Nuclear Medicine· 0 citations
Abstract Context Fusion-positive pediatric papillary thyroid carcinoma (PTC) often presents with regional nodal or distant disease, but factors explaining heterogeneity within fusion-positive tumors are incompletely defined. Objective To determine whether age, fusion group, or sex is associated with baseline N1b and/or M1 disease in fusion-positive pediatric and young adult PTC. Design Retrospective analysis of the international PEDIMAP cohort. Setting Multi-institutional pediatric and young adult thyroid carcinoma cohort. Patients Patients aged 0-25 years with PTC, documented somatic kinase fusion, and available fusion-partner information. Intervention(s) None. Main Outcome Measure(s) Advanced baseline presentation, defined as AJCC N1b and/or M1 disease. Associations were tested using Firth penalized logistic regression. Results Of 101 kinase fusion-positive PTCs identified among 646 PTCs, 2 rearranged during transfection (RET)-fusion cases were excluded because fusion-partner information was unavailable, yielding 99 fusion-positive tumors with known fusion partners: RET, n = 52; neurotrophic receptor tyrosine kinase (NTRK), n = 28; and other non-RET/NTRK kinase fusions, n = 19. Among 95 patients with evaluable N- and M-stage, 64 (67.4%) had N1b and/or M1 disease. Age 0-14 years was associated with higher odds of advanced presentation than age 15-25 years (adjusted OR, 4.67; 95% CI, 1.84-12.75; P = .001). No significant difference in advanced presentation was found between NTRK and RET fusions (adjusted OR, 0.83; 95% CI, 0.29-2.50; P = .739). Conclusion Within fusion-positive pediatric and young adult PTC, younger age was associated with greater baseline disease extent, whereas no significant difference in N1b/M1 presentation was found between RET and NTRK-fusion groups. These findings support careful baseline assessment of regional and distant disease in younger fusion-positive patients.
Sule Canberk, Zubair Baloch, A. M. Carillo et al.· Journal of the Endocrine Soc...· 0 citations
Introduction: Breast cancer remains the most prevalent malignancy among women worldwide, with prognostic outcomes and therapeutic responses differing considerably across subtypes. The conventional staging framework developed by the Union for International Cancer Control (UICC), based on the Tumor, Node, Metastasis classification, reflects anatomical stage (AS) but overlooks biological characteristics. To address this limitation, the American Joint Committee on Cancer (AJCC) introduced the Prognostic Stage (PS) in its 8th edition, which integrates biomarkers including estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and histological grade (HG). This study aimed to assess and compare the prognostic utility of UICC AS and AJCC PS in patients with high-risk luminal breast cancer. Methods: This retrospective study included patients who underwent surgery for ER-positive, HER2-negative breast cancer at Tokyo Metropolitan Komagome Hospital from 2011 to 2018. High-risk classification was defined based on MonarchE trial criteria: axillary lymph node metastasis, tumor diameter ≥5 cm, HG3, or Ki-67 ≥20%. Staging was performed using both UICC AS and AJCC PS, and prognostic values were evaluated via Kaplan-Meier survival analysis. Results: Among 105 eligible cases, 43 (41%) were downstaged when reclassified from UICC AS to AJCC PS. While UICC AS failed to yield significant stratification in terms of invasive disease-free survival (IDFS) and distant recurrence-free survival (DRFS), AJCC PS demonstrated significant prognostic discrimination (IDFS p = 0.014; DRFS p = 0.004). Conclusions: American Joint Committee on Cancer PS offers superior prognostic stratification compared to UICC AS in high-risk luminal breast cancer. Its incorporation into clinical practice may enable more personalized treatment approaches, particularly when identifying candidates for adjuvant abemaciclib therapy. Further validation through larger, prospective studies is warranted.
Age at diagnosis is an independent prognostic variable for breast cancer-specific and overall survival (OS). We previously developed a novel prognostic staging system that incorporates age and demonstrated refined risk stratification compared with the current American Joint Committee on Cancer (AJCC) staging schema. We now aim to externally validate this staging system. The National Cancer Database was used to identify adult females diagnosed with invasive breast cancer from 2010-2015. Women with prior malignancy, unknown vital status, or unknown AJCC clinical prognostic stage (CPS) variables were excluded. Serial multivariable Cox’s proportional hazards models evaluated associations between OS and CPS +/- age +/- effect modification (CPS by age interaction). Models were evaluated using concordance index (C-index). Among 663,659 patients, the median age was 60 years (IQR 51-70) and the median follow-up was 91.3 months. At last follow-up, 133,273 patients (20.1%) were dead. The model that incorporated both age and effect modification had the highest C-index (0.7852, versus 0.6881 for the model excluding age and 0.7847 for the model without effect modification), indicative of the best predictive performance. Using this model to predict OS stratified by CPS showed differential survival across the age spectrum, consistent with the initial model. Within each stage group, women diagnosed at age 40 had the best survival, whereas women at the extremes of age had inferior survival. This analysis provides external validation of our novel prognostic staging system for breast cancer. Future editions of AJCC may consider incorporating age to achieve more accurate survival predictions.
H. Johnson, Wenli Dong, Yu Shen et al.· Breast Cancer Research and T...· 0 citations