OBJECTIVES
The incidence of early-onset gastrointestinal malignancies is increasing globally; however, early-onset small bowel neuroendocrine tumors (EO-SBNETs) remain poorly characterized. We evaluated clinical characteristics, treatment patterns, incidence trends, and survival outcomes of EO-SBNETs compared with average-onset SBNETs (AO-SBNETs).
METHODS
We conducted a retrospective population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database (2004 to 2021). Patients with SBNETs were identified using ICD-O-3 histology codes and categorized as early-onset (30 to 49 y) or average-onset (≥50 y). Baseline characteristics were compared using χ2 tests. Overall survival (OS) was estimated using the Kaplan-Meier method and evaluated with multivariable Cox regression models that adjusted for demographic, socioeconomic, clinical, and treatment-related factors. Temporal incidence trends were assessed using linear regression.
RESULTS
Among 3713 patients with SBNETs, 925 (25.0%) had EO-SBNETs. EO-SBNETs were more frequently observed in females and racial and ethnic minority populations, including non-Hispanic Black and Hispanic patients (all P<0.05). Stage at diagnosis and treatment patterns, including rates of surgery, lymphadenectomy, chemotherapy, and radiation therapy, were comparable between the groups. Incidence increased significantly over time in both EO-SBNETs and AO-SBNETs (annual increase 14.9% vs. 14.8%, P<0.001), without differences in temporal trends. The median OS was not reached for AO-SBNETs and was 188 months for EO-SBNETs. On multivariable analysis, early-onset disease was independently associated with improved survival (HR=0.50, 95% CI: 0.41-0.60, P<0.001).
CONCLUSIONS
EO-SBNETs represent a rising and clinically distinct subgroup characterized by similar presentation and treatment but relatively favorable long-term outcomes compared with AO-SBNETs, suggesting potential biological differences warranting further investigation.
Matthew T. Gao, Rishi R. Patel, Jason Semprini et al.· American Journal of Clinical...· 0 citations
Background Colorectal cancer (CRC) is increasingly diagnosed in younger adults, with evidence that early-onset cases (age <50 years) differ in the spectrum of prevalent gene mutations compared with older individuals. To evaluate how these age-related differences may inform testing guidelines and therapeutic development, we examined mutation rates of the most prevalent gene mutations across four age-stratified cohorts. Patients and methods Clinicogenomic data were obtained from Memorial Sloan Kettering Center for Harmonized Onco-genomic Research Dataset and China Pan-Cancer cohorts available in cBioPortal. A total of 6762 samples were analyzed. Mutation frequencies for a comprehensive panel of the 100 most prevalent CRC genes were compared across four age groups: 18-29 (n = 79), 30-39 (n = 402), 40-49 (n = 1064), and ≥50 (n = 5217) using chi-square analysis. False discovery rate (FDR) correction for multiple comparisons was carried out using Benjamini–Hochberg procedure. Results Statistically significant variation in mutation frequency across age groups was seen in 22 key genes. APC mutations increased with age and were seen in 49.4% of patients in the 18-29 group, 69.7% in 30-39, 73.3% in 40-49, and 75.25% of patients ≥50 (P < 0.001, FDR < 0.001). The oldest cohort was more than three times more likely to have an APC mutation than the youngest [odds ratio (OR) = 3.74, 95% confidence interval (CI) 2.44-5.74, P < 0.001]. In contrast, SMAD4 mutations were twice as common in the youngest age group at 31.6% compared with those over 40, with a prevalence of 17.29% in patients 40-49, and 18.84% in patients over 50 (OR = 2.03, 95% CI 1.26-3.27, P < 0.001, FDR < 0.001). POLE mutations peaked in the 30-39 age group with a prevalence of 10.7% compared with 6.3% in patients aged 18-29, 4.9% in patients aged 40-49, and 5.9% in patients aged ≥50 (P < 0.001, FDR < 0.001). Individuals in the 30-39 group were nearly twice as likely to carry a POLE mutation compared with those over 40 (OR = 1.96, 95% CI 1.41-2.74, P < 0.001). Conclusions Differences in mutations of key genes including a lower prevalence of APC mutations and increased SMAD4 mutations in younger individuals provides further supporting evidence that early-onset CRC may represent a distinct biological subtype of CRC. Enrichment of POLE mutations in younger patients highlights the importance of expanded molecular profiling in early-onset CRC, which could help identify patients most likely to benefit from immunotherapy and advance personalized treatment strategies in CRC. Together, these findings reinforce the need to approach early-onset CRC as a distinct biological entity and ensure that appropriate molecular assays are incorporated to guide care.
L. Liu, A. Rose, A. Samaddar et al.· ESMO gastrointestinal oncolo...· 0 citations
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