Search Results (159)

Background: Sarcomatoid renal cell carcinoma (sRCC) is an aggressive RCC subtype with a poor prognosis. Although racial disparities in RCC outcomes are reported, survival patterns across racial and ethnic groups in metastatic sRCC (msRCC) remain unclear. Methods: We conducted a retrospective analysis of 2122 patients with msRCC diagnosed between 2010 and 2020 using the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized by race and ethnicity as non-Hispanic White, non-Hispanic Black, Hispanic, Asian/Pacific Islander, or American Indian/Alaska Native. Three-year cancer-specific survival (CSS) and overall survival (OS) were estimated using Kaplan–Meier methods. Multivariable Cox proportional hazards regression models were used to evaluate racial disparities in survival. Results: Non-Hispanic Black patients experienced the poorest outcomes, with 3-year CSS and OS of 9.3% and 8.6%, compared with 23.3% and 20.9% in non-Hispanic White, 22.1% and 19.0% in Hispanic, 21.2% and 19.4% in Asian/Pacific Islander, and 23.4% and 20.7% in American Indian/Alaska Native patients. Non-Hispanic Black patients were associated with higher estimated hazards of cancer-specific mortality (HR = 1.5, p < 0.0001) and overall mortality (HR = 1.5, p < 0.0001) versus non-Hispanic White. From 2010–2015 to 2016–2020, survival improved across most racial groups with the introduction of immune checkpoint inhibitors. However, non-Hispanic Black patients remained the only group with persistently inferior survival. Subgroup analysis further demonstrated worse survival for non-Hispanic Black patients in both clear cell msRCC and non-clear cell msRCC subgroups. Conclusions: Although survival was higher during the later diagnosis period, non-Hispanic Black patients with msRCC continued to have the poorest observed survival. These differences may be associated with unmeasured social, structural, socioeconomic, healthcare access, treatment, or clinical factors, but their causes cannot be determined from this observational study. Further research is needed to identify the factors underlying these survival differences. Full article

Background: Pancreatoblastoma (PB) is an exceptionally rare malignant epithelial neoplasm of the pancreas that recapitulates the developing pancreatic anlage. It is defined histologically by acinar-predominant differentiation with characteristic squamoid nests, and it may also show ductal and endocrine differentiation within the same tumor, features that distinguish it from acinar cell carcinoma and solid pseudopapillary neoplasm but that are readily overlooked. It occurs predominantly in young children, although adult-onset disease is well documented. We provide a population-based characterization of PB across the full age spectrum and benchmark it against pancreatic ductal adenocarcinoma (PDAC). Methods: Cases diagnosed between 2000 and 2021 were identified in the Surveillance, Epidemiology, and End Results (SEER) 17-registry database using site and histology codes. Cancer-specific survival (CSS) was estimated and compared, and Cox proportional hazards regression was used to explore associations with cancer-specific mortality. Results: Thirty-nine cases of PB were identified, compared with 155,924 cases of PDAC. The median age at diagnosis was 17 years (range, under 1 to 78 years); 12.8% (n = 5) were younger than 1 year. Males accounted for 69.2% (n = 27) of cases. The cohort was divided at the conventional pediatric-to-adult threshold of 18 years into a pediatric subgroup (age < 18 years; n = 20) and an adult subgroup (age ≥ 18 years; n = 19). CSS at 1 and 5 years was 95.0% and 83.5% in the pediatric subgroup, versus 67.7% and 24.6% in the adult subgroup (log-rank p < 0.001). Five-year CSS was 44.8% in males and 75.0% in females. In an exploratory multivariable model, older age was associated with higher cancer-specific mortality both as a dichotomous variable (adjusted hazard ratio [HR] for age ≥ 18 years 10.7, 95% confidence interval [CI] 2.4–48.2; p = 0.002) and, in a parallel model, as a continuous variable (adjusted HR 1.4 per 10-year increment, 95% CI 1.1–1.8; p = 0.002), indicating an age–mortality gradient. Male sex showed an association in the same direction that did not reach statistical significance (adjusted HR 3.3, 95% CI 0.96–11.6; p = 0.06). Relative to PDAC, PB was more frequently diagnosed in males and was associated with markedly superior survival (1- and 5-year CSS 81.8% and 54.9%, versus 28.8% and 4.0%). Conclusions: Pancreatoblastoma is predominantly a malignancy of young males and carries a substantially more favorable prognosis than PDAC, but outcomes differ markedly across the age spectrum, with adult-onset disease showing considerably poorer survival. Translationally, these population-level estimates support age-stratified prognostic counseling, argue for the referral of adults to centers experienced in rare pancreatic tumors, and provide a rationale for prospective molecular profiling to determine whether adult and pediatric PBs are biologically distinct and whether Wnt/beta-catenin pathway activation is therapeutically actionable. Full article

In 2010, the World Health Organization (WHO) standardized neuroendocrine neoplasm terminology, dividing these tumors by differentiation into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas. Registries such as the Surveillance, Epidemiology, and End Results (SEER) program and the National Cancer Database (NCDB) store legacy codes predating this framework, raising concern that registry-based research carries nomenclature errors into the clinical literature. We performed a scoping review of research published in 2012–2022 that used SEER and/or the NCDB to study gastroenteropancreatic neuroendocrine tumors, charting 170 articles (from 1079 citations) against the 2010 classification, with forward citation analysis (OpenAlex, Semantic Scholar) measuring downstream citation exposure. Of 141 assessable studies, 88% (n = 124) applied the nomenclature inaccurately: 82.3% included poorly or undifferentiated neoplasms within neuroendocrine tumor cohorts (mean 18.7% of the cohort) and 9.9% conflated database differentiation grade with WHO proliferation grade; appropriate usage did not improve over time. These discordant studies accumulated 7323 citations across 5145 works, with 87.9% cited by at least one review (1075 distinct reviews) and six cited by major guidelines (NCCN, ESMO, ENETS). Across research published from 2012 to 2022, nomenclature discordance was widespread, persistent throughout the study period, and present in studies frequently cited by the secondary and guideline literature. Because these cohorts incorporate more aggressive and poorly or undifferentiated neoplasms, their aggregate outcome estimates are likely biased toward a poorer prognosis, potentially overstating the aggressiveness of well-differentiated neuroendocrine tumors, particularly for prognostic estimates; this review characterized cohort composition rather than quantifying the effect on any individual study’s outcomes, and whether this bias has, in turn, affected clinical decision-making was not assessed here and remains a hypothesis for future work. Journals and guideline panels should require explicit alignment with current WHO definitions for registry-based studies. Full article

Background: Mucinous adenocarcinoma (MAC) of the colorectum is a biologically distinct histological subtype whose prognostic significance may vary substantially according to primary tumor location. The impact of anatomical site on clinicopathological characteristics and long-term survival in MAC remains incompletely characterized. This study aimed to evaluate the influence of tumor location on oncological outcomes in patients with mucinous colorectal cancer using a large population-based dataset. Methods: Patients diagnosed with mucinous colorectal adenocarcinoma between 2000 and 2023 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Operated patients were stratified by anatomical location into three groups: right colon (cecum, ascending colon, hepatic flexure, transverse colon), left colon (splenic flexure, descending colon, sigmoid colon, rectosigmoid junction), and rectum. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). Survival analyses were performed using the Kaplan–Meier method with log-rank testing. Multivariable Cox proportional hazards regression was used to assess the independent association of tumor location with survival outcomes, adjusting for age at diagnosis, year of diagnosis, sex, AJCC (American Joint Committee on Cancer) stage, tumor grade, receipt of radiotherapy and chemotherapy. Temporal trends in survival were evaluated across four consecutive diagnostic periods: 2000–2005, 2006–2011, 2012–2017, and 2018–2023. Results: A total of 40,698 patients with mucinous colorectal cancer were identified, of whom 40,174 underwent cancer-directed surgery (right colon n = 25,317; left colon n = 10,408; rectum n = 4449). The right colon was the predominant site of disease (62.9%). Median age was highest in the right colon group (74.0 years) and lowest in the rectum (65.0 years), while female sex predominated in right-sided tumors (55.7%) and male sex in rectal tumors (61.1%). Chemotherapy and radiotherapy utilization were markedly higher in the rectal group (68.6% and 64.5%, respectively) compared with the right colon (28.8% and 1.1%). Median OS was equivalent in the right and left colon groups (87.0 months each) but declined to 80.0 months in the rectal group. All pairwise CSS comparisons were statistically significant (all p < 0.001). On multivariable analysis, using the right colon as reference, the adjusted hazard ratios for CSS were 1.33 (95% CI: 1.28–1.39) for the left colon and 1.45 (95% CI: 1.34–1.57) for the rectum (both p < 0.001). Despite receiving the highest rates of multimodal therapy, rectal MAC demonstrated the worst long-term CSS across all anatomical groups. Temporal analyses revealed consistent CSS improvements in right-sided and left-sided MAC over the study period, whereas rectal MAC showed a non-linear trajectory with a plateau in the most recent diagnostic cohort (2018–2023). Conclusions: Mucinous colorectal adenocarcinoma demonstrates substantial biological and prognostic heterogeneity according to anatomical tumor location. Right-sided MAC was the most prevalent subtype and exhibited superior cancer-specific survival despite older patient age and lower treatment intensity. Rectal MAC demonstrated the worst long-term outcomes despite high utilization of multimodal neoadjuvant therapy, consistent with the established reduced responsiveness of mucinous tumors to conventional chemoradiotherapy. These findings underscore the necessity of incorporating anatomical location and tumor biology into individualized risk stratification and therapeutic planning for patients with mucinous colorectal cancer. Full article

Background: The survival benefit of primary tumor resection (PTR) in patients with synchronous metastatic primary malignant bone neoplasms (PMBNs) remains controversial. We aimed to evaluate the association between PTR and survival outcomes using a large population-based cohort with rigorous confounding control. Methods: Patients diagnosed with synchronous metastatic PMBNs (osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma) between 2004 and 2022 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were stratified by receipt of PTR. Propensity score matching (PSM; 1:1 nearest-neighbor, caliper = 0.03) was applied to balance baseline covariates. Kaplan–Meier analysis with log-rank testing and multivariable Cox proportional hazards regression stratified by matched pairs were used to assess overall survival (OS) and cancer-specific survival (CSS). Subgroup analyses were performed across four histological subtypes. Results: A total of 1046 patients were included (resection: n = 658, 62.9%; no resection: n = 388, 37.1%). After PSM, 488 patients (244 per group) were retained. In the matched cohort, PTR was independently associated with significantly improved Overall survival (OS) (HR = 0.34, 95% CI: 0.21–0.54, p < 0.001) and cancer-specific survival (CSS) (HR = 0.35, 95% CI: 0.22–0.55, p < 0.001). Subgroup analyses demonstrated significant survival benefit in osteosarcoma and chondrosarcoma (both p < 0.001), but not in Ewing sarcoma or chordoma. Conclusions: PTR is associated with a significant survival benefit in selected patients with synchronous metastatic PMBNs, particularly those with osteosarcoma and chondrosarcoma. These findings support individualized, multidisciplinary decision-making regarding surgical intervention in this population. Full article

Background: Breast cancer with isolated bone metastases at initial diagnosis represents a clinically distinct metastatic phenotype, often associated with more indolent biology and relatively favorable outcomes compared with visceral metastatic disease. The survival impact of resecting the intact primary breast tumor in de novo metastatic breast cancer remains controversial. In this study, we evaluated the association between primary breast surgery and overall survival (OS), defined as the time from diagnosis to death attributable to breast cancer, in patients presenting with isolated bone metastatic breast cancer. Methods: We performed a retrospective population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. Because the SEER variable for bone metastasis at diagnosis is available from 2010 onward and HER2-defined subtype information is available in the modern SEER era, the effective study period was defined as 2010–2021 rather than the full 2000–2021 SEER release period. Patients with breast cancer and isolated bone metastases at presentation, without evidence of lung, liver, brain, or other distant metastatic sites at diagnosis, were included. Demographic and clinicopathological variables, including age, sex, race, biologic subtype, histology, chemotherapy, radiotherapy, and primary breast surgery, were analyzed. Overall survival (OS), defined as the time from diagnosis to death attributable to breast cancer, was estimated using Kaplan–Meier methods and compared using the log-rank test. Independent prognostic factors were evaluated using multivariable Cox proportional hazards modeling. Results: A total of 6500 eligible patients were identified. Surgery of the primary breast tumor was performed in 1513 (23.3%) patients, and 62.8% received chemotherapy. Five-year overall survival (OS) was significantly higher among patients who underwent surgery than among those who did not undergo surgery (59.5% vs. 38.6%; p < 0.001). In multivariable analysis, primary breast surgery remained independently associated with improved OS (hazard ratio [HR] 0.54, 95% CI 0.48–0.62; p < 0.001). Age, histology, chemotherapy, radiotherapy, and biologic subtype were also associated with prognosis. Sex was not significant in the unadjusted analysis (p = 0.188), and the multivariable sex finding was interpreted cautiously because only 96 men were included. Conclusions: In this population-based cohort of patients with de novo breast cancer and isolated bone metastases, primary breast surgery was associated with improved survival among selected patients. However, this association should not be interpreted as causal, given the inherent limitations of observational registry data, including treatment selection, potential immortal-time bias, unmeasured metastatic burden, performance status, systemic therapy type and response, and local symptom burden, which are not fully captured in SEER. These findings support careful multidisciplinary consideration of local therapy in selected patients, while emphasizing the need for confirmation in prospectively designed studies. Full article

Background: Despite significant advances in diagnosis and treatment, gastric cancer remains a major global malignancy. This study aimed to evaluate the impact of Surveillance, Epidemiology, and End Result (SEER) stages on all-cause and cause-specific mortality in gastric cancer. Methods: This nationwide population-based cohort study analyzed data from the Cancer Public Library Database (CPLD). Patients aged ≥ 30 years diagnosed with gastric cancer between 2012 and 2019 were followed up until 31 December 2020. Cox proportional hazards models and Fine–Gray models were used to compare the risk of all-cause and cause-specific mortality based on SEER stages. The Kaplan–Meier method and cumulative incidence functions were applied to analyze cumulative incidences of all-cause and cause-specific mortality. Statistical significance was assessed using the log-rank test and Gray’s test. Additionally, a subgroup analysis was performed. Results: Among 218,491 individuals, 59,952 died during a median follow-up of 3.62 years. Compared with the localized stage, the risk of all-cause mortality was 4.31 and 24.73 times higher in patients with the regional and distant stages, respectively, after adjusting for sex, age, income, residential area, and comorbidities. The regional stage was associated with an 8.70-, 6.08-, 1.28-, and 1.43-fold higher risk of stomach cancer death, cancer death, cardiovascular death, and respiratory death, respectively. The distant stage was associated with 51.67-, 35.97-, 1.74, and 1.54-fold higher risk of stomach cancer death, cancer death, cardiovascular death, and respiratory death, respectively. Conclusions: Higher SEER stage in gastric cancer is associated with an increased risk of all-cause mortality, gastric cancer-specific mortality, overall cancer mortality, cardiovascular disease-related mortality, and respiratory disease-related mortality. Notably, cardiopulmonary mortality increased with advancing SEER stage, particularly among younger patients, underscoring the need for vigilant monitoring. Full article

Background: Pancreatic tumors in pediatric and adolescent patients are rare, and guidance on prognostication and management is limited. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database (2004–2021), we analyzed clinicopathological characteristics, treatment patterns, and survival outcomes in patients younger than 20 years with pancreatic tumors. Analyses integrated conventional survival models with machine learning approaches to identify key predictors. Results: The cohort included 203 patients, of whom 108 (53.2%) had solid pseudopapillary neoplasms (SPNs), 59 (29.1%) neuroendocrine neoplasms, 16 (7.9%) pancreatoblastomas, 5 (2.5%) adenocarcinoma variants, 4 (2.0%) acinar cell carcinomas, and 11 (5.4%) other rare histologies. Most patients had localized disease (61.1%) and underwent surgical resection (85.2%). Estimated 5-year and 10-year overall survival rates were 87.8% and 84.0%, respectively. Survival differed significantly by histology, stage, and surgery status (all log-rank p < 0.001). In multivariable analysis, SPN histology was associated with lower mortality (hazard ratio (HR) 0.03, 95% confidence interval (CI) 0.01–0.13; p < 0.001), whereas distant disease was associated with markedly higher mortality (HR 21.49, 95% CI 7.52–133.41; p < 0.001). Surgical resection was independently associated with lower mortality (HR 0.13, 95% CI 0.02–0.29; p = 0.003). Among patients with known 5-year status, the Random Forest and Gradient Boosting models achieved cross-validated area under the curve values of 0.935 ± 0.060 and 0.886 ± 0.093, respectively; stage and surgery were the dominant predictors in both models. Conclusions: Surgery remains the cornerstone of management for pediatric pancreatic tumors, and advanced analytic approaches may enhance risk stratification in this rare population. Full article

Objectives: This study aimed to investigate the impact of TDs on the survival of patients with locally advanced rectal cancer (LARC). Additionally, we propose a novel staging method that combines TDs and lymph node metastases (LNMs) to enhance prognostic accuracy. Methods: Patients with LARC were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database and a Sun Yat-sen University (SYSU) cohort. Propensity score matching (PSM) was utilized to minimize selection bias when evaluating TDs. We quantitatively stratified TDs counts and integrated them with regional LNMs to formulate a novel tumor node metastasis (TNM) staging system. Furthermore, a prognostic nomogram incorporating TDs was constructed and validated to predict survival. Results: Overall, 19,991 patients were included in the SEER database, with 2667 (13.3%) TDs-positive and 17,324 (86.7%) TDs-negative tumors. After PSM, multivariate Cox analysis reveals that TDs are an independent adverse prognostic factor (HR = 1.521, 95% CI: 1.366–1.693, p < 0.001). Patients with high-risk group (TDs > 4) at any TNM stage exhibit OS comparable to or worse than that of stage IIIC disease. For patients staged as T4N2M0, the high-risk group (TDs > 4) demonstrates OS equivalent to stage IV disease. The nomogram achieved C-indices of 0.713 (training cohort, n = 8586) and 0.789 (external validation cohort, n = 304), with AUCs of 0.774 (3-year) and 0.710 (5-year). Conclusions: The presence of TDs is associated with poorer OS, and integrating TDs with LNMs improves the accuracy of TNM staging. The nomogram (C-index = 0.789) provides enhanced prognostic stratification and survival prediction. Full article

Backgrounds: Gastric malignancies are exceptionally rare among children and young adults, and their clinicopathological characteristics and outcomes remain poorly defined. This study aimed to evaluate the demographic, clinical, and survival features of gastric cancer in patients aged ≤24 years using population-based data. Methods: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2016) for individuals ≤ 24 years with primary gastric malignancies. Cox proportional hazards models were used to identify predictors of overall survival (OS). Results: A total of 324 patients were included (mean age: 20 years; 50% female). Adenocarcinoma was the most common histologic subtype (52%), nearly half of which were signet ring cell carcinomas (46%). The majority of patients (59%) were diagnosed at stage IV. Median OS was 18 months, and 5-year OS was 49%. Children and adolescents (≤18 years) had significantly better survival than young adults (median OS: 34 vs. 15 months, p < 0.01). In multivariable analysis, advanced AJCC stage and higher lymph node ratio were independently associated with worse overall survival, while lymphoma histology and radiotherapy were linked to more favourable outcomes. Conclusions: Gastric cancers in patients ≤ 24 years often present at advanced stages and are dominated by aggressive histology. Prognosis is primarily determined by tumour stage, histological subtype, and lymph nodal burden. These population-based risk estimates support risk stratification and prognostic assessment in young patients by highlighting histology- and nodal-burden-driven prognostic strata. Full article

Purpose: Tumor location influences survival in bladder cancer, potentially due to genetic heterogeneity driven by distinct embryological origins and structural compositions. We investigate location-specific somatic gene alterations (GAs) and their potential clinical implications in muscle-invasive bladder cancer (MIBC). Methods: We explored the role of the intra-bladder tumor location in determining survival and underlying genetic alterations in MIBC patients using multiple large independent databases. We analyzed the tumor location’s impact on survival using the Surveillance, Epidemiology, and End Results (SEER) database and validated these findings using cBioPortal (CBP), which also contains gene sequencing data, enabling a comparison of GA frequency by tumor location. We investigated GA combinations to identify potential synthetic lethal (SL) combinations and co-occurrence signatures for survival prediction. Using the ROC Plotter database, we explored how significantly altered genes affect the response to immune checkpoint inhibitors (ICI). Results: An analysis of 6712 SEER and 570 CBP patients revealed significant (p < 0.001) differences in overall survival stratified by tumor location, with trigone tumors showing the worst survival. Genomic analysis identified 35 genes with location-specific alteration frequencies. Three of these genes, CDKN2A, SPTAN1, and BIRC6, were significantly predictive of ICI response, and three genes were uniquely associated with a specific location: BPTF (anterior wall), RYR1, and OBSCN (dome). Furthermore, we identified 349 SL pairs from the 35 significantly altered genes, and a co-occurrence analysis revealed two novel gene pairs associated with improved survival. Conclusions: Intra-bladder tumor location determines survival and distinct genetic profiles in MIBC. These location-specific alterations predict ICI response and identify novel synthetic lethal targets, guiding precision oncology. Full article

Objective: This study aimed to assess the impact of the number of metastatic lymph nodes (LNs) on survival and propose a subdivision of the N2b category in colorectal cancer (CRC) patients. Methods: We retrospectively analyzed from two sources: clinicopathologic data of CRC patients with stage pTxN2bM0 who initially underwent radical surgery at Cancer Hospital, Chinese Academy of Medical Sciences/National Cancer center (NCC), and patients with stage pTxN0-2bM0-1 in the Surveillance, Epidemiology and End Results (SEER) database from January 2010 to December 2015. The optimal cutoff value of the number of positive lymph nodes (PLNs) was determined based on the principle of maximum chi-square value. We constructed survival curves using the Kaplan–Meier method, assessed survival differences with the log-rank test, and conducted univariate and multivariate analyses using the Cox proportional hazard regression model. Results: A total of 68,335 CRC patients were included: 240 from the NCC cohort, and 68,095 from the SEER cohort. Within the SEER cohort, 65,189 patients had M0 stage disease and 2,906 had M1 stage disease. The optimal PLN cutoff value determined by X-tile software (Version 3.6.1) was 13. According to PLN, stage N2b patients were divided into two groups: stage N2b# (7 ≤ PLN < 13) and stage N3 (PLN ≥ 13). In the NCC cohort, the 5-year overall survival (OS) rates of stage N2b# and N3 patients were 66.0% and 45.7%, respectively (p < 0.001). In the SEER cohort, the 5-year cancer-specific survival (CSS) rate was 57.1% for stage N2b# patients compared with 40.2% for stage N3 patients (p < 0.001). The results of multivariate Cox analysis demonstrated that modified stage pN was the independent prognosis factor of OS in the NCC cohort (HR = 1.869, 95%CI:1.253–2.787, p = 0.002); modified stage pN was also the independent prognosis indicator of CSS in the SEER cohort (N3:N0, HR = 8.170, 95%CI: 7.298–9.146, p < 0.001). There was no survival difference between TxN3M0 and TxN0-2b#M0 (5-year CSS rate: 40.2% vs. 30.1%, p = 0.050; 5-year OS rate: 35.3% vs. 27.8%, p = 0.358). Conclusions: The N category served as a strong independent prognostic indicator in CRC patients. Furthermore, PLN emerged as an independent prognostic factor specifically in stage N2b CRC patients. These findings suggest that clinicians may utilize PLN for prognostic stratification and tailor adjuvant therapeutic strategies accordingly for patients diagnosed with stage N2b CRC. Full article

Background/Objectives: We describe the real-world survival and utilization of lung biopsy in Medicare patients with unresected stage I-IIB (N0) non-small-cell lung cancer (NSCLC) receiving primary stereotactic body radiotherapy (SBRT) in the US. Methods: Patients (aged ≥66 years) with unresected stage I-IIB (N0) NSCLC who received primary SBRT were identified in the SEER-Medicare database (2007–2020) and followed from SBRT initiation until death/data end. Outcomes included overall and disease-stage-specific real-world event-free survival (rwEFS), overall survival (OS), lung cancer-specific cumulative incidence of death, and time to death or distant metastasis (TDDM). rwEFS, OS, and TDDM were described using Kaplan–Meier analysis. Median times from lung biopsy to SBRT were summarized. Results: Of 3014 patients (median follow-up: 2.9 years), 2302 (76.4%), 454 (15.1%), 168 (5.6%), and 90 (3.0%) had stage IA, IB, IIA, and IIB disease, respectively. The mean age at diagnosis was 77.3 years, 37.7% were male, and 86.9% were White. Overall, the 5-year rwEFS rate was 23.8% (median 26.2 months), the 5-year OS rate was 42.3% (median 48.9 months), and the 5-year lung cancer-specific cumulative incidence of death was 25.3%. rwEFS and OS rates declined with more advanced disease stage at diagnosis. Most patients (90.1%) underwent lung biopsy within 12 months before SBRT. Conclusions: Among older US patients with unresected NSCLC receiving SBRT, prognosis remains limited, with many deaths due to non-lung cancer causes. Recurrence and survival were lower among subgroups with more advanced disease. These findings benchmark real-world outcomes for future studies assessing novel strategies in this patient population. Full article

Background: Social determinants of health critically impact outcomes along the care continuum of patients with hepatocellular carcinoma (HCC). This systematic review summarizes the effect of socioeconomic status (SES) factors on HCC outcomes in the United States. Methods: Electronic databases were queried for the concepts of “liver cancer”, “health disparities”, and “socioeconomic factors” on 1 March 2021. Eligible studies included an individual- or area-level SES measure such as income, education, employment, and insurance and one of the following outcomes across the clinical continuum of HCC care: incidence, screening/surveillance, diagnosis, treatment, survival, and end-of-life. Results: Of 3331 studies screened, a total of 63 studies encompassing 179 separate analyses were included in our narrative synthesis: 13 on incidence, 5 on surveillance, 19 on diagnosis, 79 on treatment, 61 on survival, and 2 on end-of-life. Insurance was the most frequent SES measure represented (50%), followed by mostly area-level income (39%), education (9%), and employment (2%). The included studies were heterogeneous regarding both SES definitions (e.g., individual vs. area-level measures) and outcome reporting. Trends of worse outcomes were generally observed with lower indicators across all SES domains and HCC outcomes, particularly in analyses using national cancer registry data (e.g., SEER and NCDB). Unadjusted racial and ethnic disparities in outcome were attenuated in six out of 23 analyses that adjusted for an SES measure. Conclusions: Our findings highlight the need for social risk screening and interventions early in the HCC care pathway. Future research should focus on HCC surveillance and end-of-life/survivorship, with greater emphasis on examination of modifiable individual-level social determinants. Full article

Background/Objectives: Metformin is one of the most frequently used concomitant medications among prostate cancer (PCa) patients. However, the effects of metformin on all-cause and PCa-specific mortality among men diagnosed with advanced/metastatic PCa treated with androgen-deprivation therapy (ADT) remain poorly understood, but they may be specifically explained by emulating a target trial. Methods: We emulated a target trial of metformin therapy and survival using observational data on 7361 patients diagnosed with advanced PCa, who were treated with ADT, from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2008–2019), with completed follow-up until 2020. We included patients with diabetes, and participants were assigned as either “initiator of metformin within 6 months after advanced PCa diagnosis” or “non-initiator of metformin.” We estimated mortality risks using Cox proportional hazards models with adjustment for risk factors via inverse probability weighting using both intention-to-treat and per-protocol analyses. Results: Over 13 years of follow-up, with a maximum 3 years of follow-up after PCa diagnosis, all-cause mortality occurred in 52 metformin initiators (47.7%) versus 3052 non-initiators (42.1%), while PCa-specific mortality occurred in 36 initiators (33.0%) versus 1919 non-initiators (26.5%). In the intention-to-treat analysis, metformin initiation was not associated with all-cause mortality (Hazard Ratio [HR] = 1.38, 95% CI: 0.98–1.95) or PCa-specific mortality (HR = 0.99, 95% CI: 0.63–1.55). Similarly, in per-protocol analysis, there was no evidence of risk reduction with all-cause (HR = 1.20, 95% CI = 0.80–1.81) or PCa-specific mortality (HR = 1.45, 95% CI = 0.88–2.38) after adjusting for time-varying covariates and allowing a 30-day gap for metformin discontinuation, adjusted for via inverse probability weighting. Conclusions: Our findings align with prior randomized trials showing no survival benefit of metformin in advanced PCa patients receiving ADT. Timing of metformin discontinuation also showed no significant effect. However, the small size of the metformin initiator group precluded subgroup analyses for hormone-sensitive (HSPC) and castrate-resistant prostate cancer (CRPC), limiting our ability to explore potential differential effects. Full article