Gootzen TA, Hermens RP, van Gelder MM
… +23 more, Heijnen E, van Bommel MH, Apperloo MJ, Zanten MMB, Coppus SF, Custers JA, van Doorn HC, Gaarenstroom KN, Harmsen MG, intHout J, Knippenberg M, van Lonkhuijzen LR, Mourits MJ, Piek JM, Schuurman TN, Simons M, Slangen BF, Tros R, Vos MC, Zweemer RP, Kets CM, de Hullu JA, Steenbeek MP
PURPOSE: BRCA1/2 pathogenic variant (PV) carriers have an increased risk of tubo-ovarian cancer. They are recommended to have a risk-reducing salpingo-oophorectomy around age 40, resulting in premature menopause. The alt...PURPOSE: BRCA1/2 pathogenic variant (PV) carriers have an increased risk of tubo-ovarian cancer. They are recommended to have a risk-reducing salpingo-oophorectomy around age 40, resulting in premature menopause. The alternative risk-reducing salpingectomy (RRS) with delayed oophorectomy (DO) postpones this. We present the five year results of a nationwide preference trial (TUBA study) comparing menopause-related quality of life (QoL) after RRS/DO to salpingo-oophorectomy. METHODS: Premenopausal BRCA1/2-PV carriers aged 25 to 40 (BRCA1) or 25 to 45 (BRCA2) chose RRS/DO or salpingo-oophorectomy with or without hormonal replacement therapy (HRT). We compared QoL (Greene Climacteric Scale) between RRS/DO and salpingo-oophorectomy without HRT five years after surgery using linear mixed models. Secondarily, RRS/DO was compared to salpingo-oophorectomy with HRT. Women who underwent oophorectomy in the RRS/DO group were excluded in a sensitivity analysis. RESULTS: In total 410 (71.9%) participants chose RRS/DO and 160 (28.1%) salpingo-oophorectomy. Seventy-three (17.8%) participants underwent oophorectomy within five years after salpingectomy. The adjusted mean difference (aMD) in QoL was 1.8 (95%-confidence interval (CI) -0.6; 4.3) after salpingo-oophorectomy without HRT and 1.4 (95%-CI -0.4; 3.1) after salpingo-oophorectomy with HRT compared to RRS (with and without oophorectomy) at five years follow-up. The sensitivity analysis showed that QoL decreased less after RRS before oophorectomy compared to salpingo-oophorectomy without (aMD 2.4, 95%-CI 0.1; 4.8) and with HRT (aMD 1.9, 95% CI 0.1; 3.7). CONCLUSION: Postponing oophorectomy is key in preventing deterioration of QoL. QoL was similar five years after salpingectomy (with and without oophorectomy) compared to salpingo-oophorectomy (regardless of HRT use). However, QoL was higher when comparing salpingectomy without oophorectomy to salpingo-oophorectomy (regardless of HRT use).
BACKGROUND: The Affordable Care Act (ACA) expanded Medicaid eligibility to states on staggered timelines, creating a natural experiment to assess health policy effects on colorectal cancer (CRC) outcomes. METHODS: We con...BACKGROUND: The Affordable Care Act (ACA) expanded Medicaid eligibility to states on staggered timelines, creating a natural experiment to assess health policy effects on colorectal cancer (CRC) outcomes. METHODS: We conducted a retrospective quasi-experimental cohort study using the SEER database (2006 to 2019). Patients with CRC <65 years were included in primary analyses; a EOCRC cohort aged <50 years was examined. States were classified by Medicaid expansion timing, and each expansion group was propensity score-matched against non-expansion controls. The primary analysis used pooled Bayesian difference-in-differences survival models with censoring at 36 months, with sensitivity analyses at 60 months and uncapped follow-up. Secondary Bayesian logistic models evaluated stage at diagnosis and receipt of surgical resection. Results are reported as hazard ratios (HR) or odds ratios (OR) with 95% credible intervals (CrI) and posterior probabilities of benefit. RESULTS: In pooled analyses among patients younger than 65 years, Medicaid expansion was associated with reduced mortality (36-month HR = 0.86; 95%CrI, 0.81 to 0.92; P(HR < 1)>0.999), with consistent findings across follow-up endpoints. Survival benefit was larger among patients with early-onset CRC (age <50 years). No consistent association was observed among Medicare-eligible patients aged ≥65. Medicaid expansion was not associated with population-level shifts in stage at diagnosis or increased surgical resection. CONCLUSION: Medicaid expansion under the ACA was associated with a high probability of improved CRC survival among non-Medicare-eligible adults, including patients with early-onset disease. Survival gains occurred without corresponding changes in stage or surgical treatment, suggesting benefits mediated through improved access, continuity, and delivery of cancer care.
Roshani S, Boekel NB, Van Leeuwen FE
… +21 more, Rademakers SE, Roesink J, Schippers MGA, Ta BDP, Plattel WJ, Zijlstra JM, Schinagl DAX, Nijziel MR, Ong F, Schimmel EC, Posthuma EFM, Daniels LA, Böhmer LH, Muller K, Koene HR, Te Boome LCJ, Bilgin YM, De Jongh E, Janus CPM, Aleman BMP, Schaapveld M
J Natl Cancer Inst
· 2026 Mar · PMID 41942100
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BACKGROUND: Hodgkin lymphoma (HL) patients are at increased risk of developing lung cancer (LC), especially after chest radiotherapy (RT). However, there are no tools to predict LC risk for different HL treatments. METHO...BACKGROUND: Hodgkin lymphoma (HL) patients are at increased risk of developing lung cancer (LC), especially after chest radiotherapy (RT). However, there are no tools to predict LC risk for different HL treatments. METHODS: In a cohort of 5,370 ≥ 5-year HL survivors aged 15 to 50 years at HL diagnosis and treated in the Netherlands between 1965 to 2012, we used RT fields and prescribed dose to estimate mean lung dose (MLD). The twinning method was used to divide the cohort into homogenous parts: 80% for model development and 20% for validation using Inverse Probability of Censoring Weighting (IPCW) Area Under the Curve (AUC). Cox proportional hazards models allowing for time-dependent coefficient(s) were used to model time from HL diagnosis to LC and LC-free death as competing event for predicting absolute LC risk up to 30 years after HL diagnosis. RESULTS: Treatment information was composed of supra-diaphragmatic RT in 75.2% of patients with median MLD of 15.8 Gray. During follow-up, 218 survivors developed LC. Older age, male gender, smoking at HL diagnosis and higher MLD were associated with higher LC risk. The median estimated 30-year absolute LC risk in our cohort was 1.2% (Interquartile range (IQR): 0.8%-1.9%) in non-smokers and 6.9% (IQR: 4.6%-10.9%) in smokers at HL diagnosis. The 20- and 30-year IPCW AUCs were 0.79 (95% Confidence interval (CI): 0.73-0.85) and 0.75 (95% CI: 0.69-0.81), respectively. CONCLUSION: We developed a well-calibrated prediction tool that estimates long-term risk of LC with good discrimination based on patient characteristics and MLD, allowing application in HL survivors and contemporary HL patients.
Sullivan SM, Lane J, Standafer A
… +11 more, Mcfeeters J, Hubbard AK, Langer EK, Hooten AJ, Roesler MA, Gell JJ, Krailo M, Frazier AL, Amatruda JF, Pankratz N, Poynter JN
J Natl Cancer Inst
· 2026 Mar · PMID 41941753
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BACKGROUND: Germ cell tumors (GCTs) are heterogeneous neoplasms arising from primordial germ cells. While genome-wide association studies (GWAS) have identified numerous susceptibility loci for adult testicular GCTs (TGC...BACKGROUND: Germ cell tumors (GCTs) are heterogeneous neoplasms arising from primordial germ cells. While genome-wide association studies (GWAS) have identified numerous susceptibility loci for adult testicular GCTs (TGCTs), the heritable basis of pediatric TGCT and GCTs that arise outside the testes remain poorly understood. METHODS: We conducted a multi-ancestry GWAS of pediatric GCTs, including 1,927 cases from the Germ Cell Tumor Epidemiology Study (GaMETES) and 10,601 controls. Cases were diagnosed with testicular (n = 678), ovarian (n = 441), intracranial (n = 435), and extragonadal (n = 373) GCT between the ages of 0 to 19 years. RESULTS: We identified four loci reaching genome-wide significance, including variants near BAK1 (chr 6: rs3831846), SPRY4 (chr 5: rs12515244), DMRT1 (chr 9: rs10815910), and DEPTOR (chr 8: rs13277786). Additional genome-wide significant associations were identified in subgroup analyses, including six loci for intracranial GCTs (rs2758612 [PMF1/BGLAP], rs9854760 [PLCL2], rs6851498 [KIT], rs11816992 on chromosome 10, rs3830273 [TFAM], and rs13054014 [LZTR1]), one locus for testicular GCT (rs1907702 [KITLG]), and one locus for males (rs4610628 [MAD1L1]). After Bonferroni correction, 18 of 78 previously reported TGCT loci were significantly associated with GCT overall or in at least one subgroup with a particularly strong correlation between TGCT and iGCT effect estimates (rho = 0.63, P = 5.5x10-10). Expression quantitative trait locus (eQTL) analyses identified candidate genes in the regions identified on chromosome 6 (BAK1, LINC003366, and ITPR3) and chromosome 8 (DEPTOR and RP11-760H22.2). CONCLUSIONS: Our data support a role for germline genetic variation in the development of GCT in locations outside the testes and highlight shared genetic architecture across age group and tumor location.
Tregear ML, Verduzco-Aguirre HC, Shkabari B
… +10 more, Koven R, Scowcroft H, Venkatash V, Brundage MD, Chidebe RC, Eisenhauer EA, Gyawali B, Sirohi B, Booth CM, Jackson CG
J Natl Cancer Inst
· 2026 Mar · PMID 41941752
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BACKGROUND: Randomized controlled trials (RCTs) are the foundation of oncology drug development, yet increasing concern exists that some prioritize regulatory approval over outcomes that matter to patients. The Common Se...BACKGROUND: Randomized controlled trials (RCTs) are the foundation of oncology drug development, yet increasing concern exists that some prioritize regulatory approval over outcomes that matter to patients. The Common Sense Oncology (CSO) initiative was founded to reorient research toward patient-valued endpoints. The CSO Patient Priorities Working Group sought to co-develop a pragmatic, patient-centred framework articulating values and actions to guide the design, conduct, and reporting of oncology RCTs. METHODS: A multi-phase, mixed-methods process included literature review, thematic analysis, and international stakeholder engagement. Eight focus groups were held between April 2024 and January 2025 with 131 participants across seven countries, including people with lived cancer experience, advocates, clinicians, and trialists. Feedback from surveys and structured discussions-both quantitative ratings and qualitative insights-informed iterative framework refinement. RESULTS: The final framework defines nine core values with associated actions meaningful research question, patient partnerships, informed consent, meaningful benefit, generalizability, optimal comparator arm, minimal participant burden, timely feedback of results, and clear dissemination. All values received high endorsement (median 8 to 9 on a 9-point numeric rating scale [from 1 (least important) to 9 (most important)]). Qualitative analysis emphasized meaningful endpoints, transparent communication, equitable inclusion, fair compensation, and plain-language consent. CONCLUSIONS: The CSO Values to Action Framework provides a validated, internationally informed structure for trialists, ethics boards, funders, and advocates. It offers a practical tool to align oncology research with what matters most to patients, promoting more ethical, inclusive, and relevant clinical trials.
Chia BJ, Allegra C, Krishnamurthi S
… +3 more, Lieu C, Loree JM, Shi Q
J Natl Cancer Inst
· 2026 Mar · PMID 41941600
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BACKGROUND: Surrogate endpoints are increasingly used as the basis of cancer drug approvals. A strong association between treatment effects on the surrogate and true endpoint is essential for their validation as reliable...BACKGROUND: Surrogate endpoints are increasingly used as the basis of cancer drug approvals. A strong association between treatment effects on the surrogate and true endpoint is essential for their validation as reliable endpoints. We assess the current evidence of trial-level surrogacy for colorectal cancer (CRC) endpoints through a novel framework. METHODS: We developed a framework to grade the quality of oncology surrogate endpoints in 7 domains of the surrogate relationship Data source quality (A-B); disease setting homogeneity (0 to 3); uniformness of surrogate and true endpoint definitions (0 to 3); number of trials evaluated (0 to 4); individual (0 to 2) and trial-level associations (0 to 8). We screened PubMed using keywords and MeSH terms for meta-analyses published before 07/06/2024 validating surrogate endpoint associations across CRC trials. Two reviewers blindly assessed each article before reaching a consensus score. The main outcomes were framework-derived evidence scores and reported trial-level associations (R2) with overall survival (OS). RESULTS: Eighteen articles were identified, containing 39 evaluations of 12 unique surrogate endpoints for OS. Evidence scores ranged from B6-A23. Only disease-free survival (DFS) consistently demonstrated high-quality evidence of trial-level surrogacy (≥A18, median R2 = 0.92). Progression-free survival (PFS) and objective response rate (ORR) were low-quality surrogates in metastatic CRC (PFS B6-A15, median R2 = 0.55; ORR: B6-A13, median R2 = 0.33). Other evaluated endpoints demonstrated as unreliable surrogates. CONCLUSION: DFS shows high-quality surrogacy in stage II/III colon cancer. Endpoints identified in the metastatic setting demonstrate inconsistent surrogacy evidence. Re-assessment and identification of new endpoints is warranted, particularly with immunotherapy.
Agostinetto E, Gentile G, Samy F
… +12 more, Di Cosimo S, Aftimos P, Pondé N, Eiger D, Lambertini M, Cameron D, Kiermaier A, Bailey A, Viale G, Loi S, Piccart M, de Azambuja E
BACKGROUND: Responses to anti-human epidermal growth factor receptor 2 (HER2) therapy can vary based on estrogen receptor (ER) expression and HER2 gene amplification. This study assessed the magnitude of benefit by addin...BACKGROUND: Responses to anti-human epidermal growth factor receptor 2 (HER2) therapy can vary based on estrogen receptor (ER) expression and HER2 gene amplification. This study assessed the magnitude of benefit by adding pertuzumab to trastuzumab and chemotherapy by ER and HER2 levels in the APHINITY trial. METHODS: APHINITY (NCT01358877; BIG 4 to 11) was a randomized, double-blind, phase III trial comparing pertuzumab vs placebo added to adjuvant trastuzumab and chemotherapy in 4804 HER2-positive early breast cancer patients. The primary endpoint of this exploratory analysis was invasive disease-free survival (IDFS). Subgroup analyses used Cox models across four groups defined by HER2 FISH ratio and ER status, adjusted for treatment arm, chemotherapy regimen, and nodal status or protocol version. Tumors with FISH ratio <2 were excluded, leaving 4782 evaluable cases. HER2 FISH ratio was classified as low (2 ≤ ratio <5) or high (≥5), and ER expression by IHC as negative or positive using 1% and 10% cut-offs. IDFS, HER2 FISH ratio, and ER expression were also analyzed by intrinsic molecular subtype. RESULTS: All subgroups benefited from pertuzumab, with the largest reduction in HER2 FISH-low/ER-positive tumors (HR 0.70, 95% CI 0.51 to 0.95). Other subgroups showed smaller benefits, with HER2 FISH-high/ER-negative tumors having the least numerical improvement (HR 0.85, 95% CI 0.59 to 1.25). No significant IDFS differences were observed between HER2-enriched and non-HER2-enriched tumors. CONCLUSIONS: Pertuzumab numerically improved IDFS in all subgroups, greatest in HER2 FISH-low/ER-positive tumors. These exploratory findings are hypothesis-generating and support prospective validation of biomarker-guided strategies. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT01358877.
Jayasekera J, Hooshmand S, Strassle PD
… +19 more, Schneider J, Mensah GA, Mensah L, George S, Kelly YO, Baumann MM, Li Z, McHugh TA, Celone M, Sylte DO, La Motte-Kerr W, Bhangdia K, Force LM, Murray CJL, Alvarez CS, Choi K, Mokdad AH, Dwyer-Lindgren L, Pérez-Stable EJ
J Natl Cancer Inst
· 2026 Apr · PMID 41934099
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BACKGROUND: We evaluated county-level variations in racial and/or ethnic disparities in breast cancer mortality rates across the U.S. over a 20-year period. METHODS: Validated small-area estimation models were used to ca...BACKGROUND: We evaluated county-level variations in racial and/or ethnic disparities in breast cancer mortality rates across the U.S. over a 20-year period. METHODS: Validated small-area estimation models were used to calculate breast cancer mortality rates by age and race and/or ethnicity among females across all U.S counties from 2000 to 2019. The estimates were corrected for misreporting of race and/or ethnicity on death certificates and age-standardized to the 2010 U.S. Census. RESULTS: Age-standardized national breast cancer mortality rates declined between 2000 to 2019, from 33.6 (95% Uncertainty Interval 33.4 to 33.9) to 24.8 (24.6 to 25.0) deaths per 100,000 females. However, there were variations in breast cancer mortality rates across racial and/or ethnic populations at the county level. For instance, 243 of 1,478 counties showed increasing breast cancer mortality rates from 2000 to 2019 among Latina females aged <50 years (absolute increase (median): 0.23 deaths per 100,000; maximum: 1.0). County-level patterns for American Indian/Alaska Native females aged 50 to 74 years showed increasing breast cancer mortality rates across 108 of 474 counties (median: 4.4 per 100,000; max: 17.5). The largest county-level increases were seen among American Indian/Alaska Native (184 of 474 counties; median: 15.2 per 100,000; max: 124.0) and Asian (589 of 667 counties; median: 14.1 per 100,000, max: 41.0) females aged ≥75 years. CONCLUSIONS: Despite a substantial decrease in overall breast cancer mortality rates across all female populations combined in the U.S., there were significant county-level variations in breast cancer mortality rates by race and/or ethnicity.
Ng DQ, Heshmatipour M, Trudeau J
… +13 more, Sridhar A, Pluimer B, Drayson OGG, Lavasani SM, Parajuli R, Lee S, Agrawal A, Acharya MM, Limoli CL, Harris RE, Xie L, Malik S, Chan A
J Natl Cancer Inst
· 2026 Apr · PMID 41926740
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BACKGROUND: We conducted a randomized, double-blinded pilot trial to compare the impact of two electroacupuncture (EA) regimens on co-occurring neuropsychiatric symptoms among breast cancer survivors (BCS). METHODS: BCS...BACKGROUND: We conducted a randomized, double-blinded pilot trial to compare the impact of two electroacupuncture (EA) regimens on co-occurring neuropsychiatric symptoms among breast cancer survivors (BCS). METHODS: BCS who self-reported cognitive impairment, fatigue, insomnia, or psychological distress were randomized (1:1) to receive ten weekly EA to target either neuropsychiatric-specific (nEA) or non-neuropsychiatric-specific (sEA) acupoints. Primary endpoints were the within-group pre-post effect sizes (Glass's Δ) in symptom severities, adjusted for multiple comparisons (p-adjusted). Outcomes were assessed using neurocognitive tests (CANTAB®), PROs (FACT-Cog, MFSI-SF, EORTC QLQ-C30), plasma biomarkers, and neuroimaging. Responders were defined by reliable change index (for objective cognition) or MCID (for PROs). RESULTS: Thirty-five were recruited, with 30 (86%) completing all sessions. The mean (±SD) age was 58.2 (±12.2) years, and 86% reported co-occurring symptoms. Following treatment, the nEA group demonstrated significant improvements in attention (T3: Δ = 0.562, T4: Δ = 0.708, both p-adjusted < 0.05) and distress (T3: Δ = 0.764, T4: Δ = 0.711, both p-adjusted < 0.05). More responders were observed after nEA treatment for objective cognition (42.9% vs 12.5%) and distress (50% vs 37.5%). nEA-treated participants showed increased gray matter volume compared to sEA (p = 0.033), which positively correlated with better attention function (r = 0.69, p = 0.020). nEA-related improvements in memory and response speed were associated with reduced connectivity in the Default Mode Network (DMN-SFG, r=-0.93, p < 0.01) and increased connectivity in the Dorsal Attention Network (DAN-SMG, r = 0.86, p < 0.001), respectively. All adverse events were grade 2 or lower. CONCLUSIONS: EA targeting neuropsychiatric-specific acupoints suggests improvements in cognition and distress symptoms in BCS, warranting validation in larger, multicenter trials. CLINICALTRIALS.GOV: NCT05283577.
Shojaie B, Teepen JC, Winter DL
… +36 more, Gardner MP, Kaiser M, Grabow D, Ronckers CM, Byrne J, Skinner R, Alessi D, Baqaeen H, Allodji RS, Van Der Pal HJ, Jankovic M, Bagnasco F, Steliarova-Foucher E, Spycher BD, Sommer G, Bárdi E, Gudmundsdottir T, Maule MM, Michel G, Muraca M, Gunnes MW, Kenborg L, Hjalgrim H, Sacerdote C, Jakab Z, Haupt R, Wiebe T, Terenziani M, Zaletel LZ, Kremer LCM, Kuehni CE, Lähteenmäki PM, De Vathaire F, Hjorth L, Hawkins MM, Reulen RC
J Natl Cancer Inst
· 2026 Mar · PMID 41915055
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BACKGROUND: Survivors of childhood cancer are at risk of subsequent primary melanoma (SPM), but the magnitude of the risk after different childhood cancer types and beyond age 50 remains inadequately characterised. We qu...BACKGROUND: Survivors of childhood cancer are at risk of subsequent primary melanoma (SPM), but the magnitude of the risk after different childhood cancer types and beyond age 50 remains inadequately characterised. We quantified risks in the largest cohort of childhood cancer survivors worldwide. METHODS: The PanCareSurFup cohort includes 68,002 five-year childhood cancer survivors across Europe (diagnosed 1940 to 2008). SPM risks were quantified using standardised incidence ratios (SIRs), absolute excess risks (AERs), cumulative incidence and relative risks (RRs). RESULTS: Over 1,239,675 person-years, 197 SPMs were ascertained whereas 84.9 were expected (SIR = 2.3, 95%CI = 2.0 to 2.7). Although the SIR decreased with attained age (Ptrend<0.001), it remained increased at 2.1-fold (95%CI = 1.5 to 3.1) age 50+. By age 65, cumulative incidence was 1.2% (0.8% expected). Of all cancer types, heritable retinoblastoma survivors had the greatest risk (SIR = 16.5, 95% CI = 10.8 to 25.3; AER = 94.4, 95% CI = 59.9 to 148.9), with cumulative incidence of 3.3% at age 50 and 5.5% at age 60. Survivors treated with radiotherapy had a 70% greater risk than those treated without (RR = 1.7, 95% CI = 1.1 to 2.7) increasing to 4-fold age 50 + (RR = 3.9, 95%CI = 1.1 to 13.9). For chemotherapy, no significant association was found (RR=0.9, 95%CI = 0.5 to 1.6). CONCLUSIONS: Childhood cancer survivors, particularly those with heritable retinoblastoma and those treated with radiotherapy, remain at increased risk of melanoma beyond age 50. Current survivorship guidelines focus principally on treatment history; however, our findings suggest that long-term follow-up guidelines should additionally include childhood cancer type and attained age as risk-stratifying factors, particularly where individual treatment records are unavailable.
Mitchell AP, Lam MB, Carlin C
… +5 more, Tyan K, Mooghali M, Zakaria Z, Ramachandran R, Jung J
J Natl Cancer Inst
· 2026 Mar · PMID 41912420
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Private equity (PE) acquisition of medical practices has been associated with increased prices and use of lucrative treatments. Using Medicare data 2015 to 2021, we compared the prevalence of low-value cancer treatments...Private equity (PE) acquisition of medical practices has been associated with increased prices and use of lucrative treatments. Using Medicare data 2015 to 2021, we compared the prevalence of low-value cancer treatments between PE-owned and non-PE-owned practices. The five low-value treatments were: granulocyte colony stimulating factors (GCSF) for low-risk chemotherapy; denosumab for castration sensitive prostate cancer; nab-paclitaxel for breast or lung cancer; addition of bevacizumab for ovarian cancer; and biologic drugs with biosimilar alternatives. The primary outcome was receipt of a low-value treatment. Comparing patients diagnosed when their oncologist was vs was not practicing at a PE-owned address, adjusted prevalence differences of low-value treatments were: -2.8%-points (-5.5 to -0.2) for GCSF; +3.7%-points (-7.3 to 14.7) for denosumab; -0.7%-points (-3.9 to 1.5) for nab-paclitaxel; -6.5%-points (-12.5 to -0.4) for bevacizumab; and -2.9%-points (-6.0 to 0.2) for biologics. Overall, PE ownership was not associated with increased prevalence of low-value cancer treatments.
Grobman B, Lamba N, Catalano PJ
… +5 more, Tanguturi SK, Rahman R, Haas-Kogan DA, Wen PY, Aizer AA
J Natl Cancer Inst
· 2026 Mar · PMID 41912413
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BACKGROUND: Generalizable, large-scale data describing outcomes and treatment approaches for older adults with brain metastases remain limited. In this investigation, we evaluated prognosis and patterns of care in this p...BACKGROUND: Generalizable, large-scale data describing outcomes and treatment approaches for older adults with brain metastases remain limited. In this investigation, we evaluated prognosis and patterns of care in this population over time, with particular attention to the potential impact of social determinants of health. METHODS: We used the SEER-Medicare database to delineate survival, treatment patterns, and disparities among patients aged ≥65 years with brain metastases diagnosed between 2010 to 2020. Survival was assessed with Kaplan-Meier methods and multivariable Cox regression. RESULTS: This study included 67,832 patients (51% female). The median survival from diagnosis of brain metastases was 3.42 months, improving modestly from 2.99 months in 2010 to 3.88 months in 2019. Higher zip-code-level annual income (HR 0.98 per $10,000 increase, 95% CI: 0.97 to 0.98, p < 0.001) and higher rates of high school graduation (HR 0.98 per 10% increase, 95% CI: 0.97 to 0.99, p = 0.001) were associated with lower mortality. Among patients managed with brain-directed radiation, 62% and 38% received non-stereotactic (inclusive of whole brain radiation) and stereotactic approaches, respectively. Use of stereotactic radiation increased from 22% in 2010 to 54% in 2019. Compared to White patients, Black patients (HR 0.79, 95% CI: 0.73 to 0.86, p < 0.001) and Hispanic patients (HR 0.87, 95% CI: 0.79 to 0.95, p = 0.002) were less likely to receive stereotactic radiation. CONCLUSIONS: The prognosis among older patients with brain metastases remains poor. Many patients continue to receive non-stereotactic approaches. Further work to improve the prognosis of older patients with brain metastases and optimize patterns of care is needed.
Etzioni R, Gogebakan K, Gulati R
… +6 more, Owens L, Lange J, Kessler L, Smith R, Schrag D, Robbins HA
J Natl Cancer Inst
· 2026 Mar · PMID 41912411
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We are at a watershed moment in the history of early cancer detection in which many novel tests are poised to become available for population screening. An ongoing debate concerns how to properly evaluate these tests and...We are at a watershed moment in the history of early cancer detection in which many novel tests are poised to become available for population screening. An ongoing debate concerns how to properly evaluate these tests and specifically whether a shorter-term, incidence-based outcome might substitute for cancer mortality as an endpoint in randomized trials of screening test efficacy. An incidence-based endpoint promises to reduce time and resources, but there is no framework for how studies using this endpoint should report results and how they should be interpreted in terms of clinical utility. We consider whether publication of incidence-based results ahead of any mortality results could result in adoption of new screening tests ahead of reliable mortality results becoming available. We argue that guardrails are needed for this scenario, including standards for conduct and reporting of trials with incidence-based endpoints to assure valid interpretation of clinical utility. For example, information regarding the type and timing of tests used for diagnostic workup in screen and control groups will be needed. Clinicians and policy makers will need to determine acceptable measurements and magnitudes of this modified measure of test efficacy. The roles of incidence-based and mortality-based endpoints in determining practice standards will need to be defined, along with specifications for permissible adjunct evidence, such as modeling studies and real-world data. As screening trials for new multi-cancer tests will soon begin to report incidence-based results, resolution of these questions is a matter of urgency.
Iannantuono GM, Sganga S, Giovagnoli T
… +22 more, Mastrantoni L, Floudas CS, Giannarelli D, Spinazzola A, Filetti M, Lo Bianco F, Vitale A, Rosenfeld R, Lombardi P, Giudice E, Messina G, Ceccarelli A, Gulley JL, Fabi A, Carbognin L, Rossi A, Mazzuferi M, Altamura V, Maiolatesi G, Gatto A, Bria E, Daniele G
J Natl Cancer Inst
· 2026 Mar · PMID 41902835
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BACKGROUND: Early termination (ET), defined as the discontinuation of a trial before its planned completion, remains poorly characterized in phase 1 cancer trials. We aimed to: (i) identify reasons for ET in phase 1 tria...BACKGROUND: Early termination (ET), defined as the discontinuation of a trial before its planned completion, remains poorly characterized in phase 1 cancer trials. We aimed to: (i) identify reasons for ET in phase 1 trials and compare them with those in late-phase studies; (ii) investigate temporal patterns and factors associated with ET in phase 1 trials. METHODS: Trials on solid tumors initiated between 2018 and 2023 were identified using the "Aggregate Analysis of ClinicalTrials.gov" database. We compared the reasons for ET between phase 1 and phase 2 to 3 trials using the Chi-squared test. We estimated the cumulative probability of ET over time and used a multivariable logistic regression model to investigate determinants of ET. RESULTS: We included 2301 studies: 1740 phase 1 and 561 phase 2 to 3 trials. "Sponsor/strategic decisions" was the most common reason for ET in phase 1 trials (51.1%), while "poor accrual" predominated in phase 2 to 3 trials (35.5%; p < 0.001). The probability of ET in phase 1 trials increased rapidly between 10 and 30 months after initiation and plateaued after 60 months. Factors associated with a lower probability of ET included academic funding and conduct in Europe, Asia, or Oceania. Conversely, trials conducted globally or enrolling patients with thoracic or gastrointestinal cancers were more likely to discontinue prematurely. CONCLUSIONS: Phase 1 trials are primarily discontinued for "sponsor/strategic decisions". Funding source, tumor type, and geographic location of recruiting centers are independently associated with ET. The early peak in ET probability marks a critical window for interventions to improve trial sustainability.
Kaul M, Scott CG, Wadzinske A
… +13 more, Banerjee I, Hursh D, Norman A, Wu FF, Medero RC, Couch F, Pruthi S, Kontos D, McCarthy AM, Olson J, Winham S, Kerlikowske K, Vachon CM
J Natl Cancer Inst
· 2026 Mar · PMID 41885411
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BACKGROUND: Artificial intelligence (AI) -based, mammography breast cancer (bc) risk prediction models show improved discriminatory accuracy relative to clinical risk models. However, data on their calibration are limite...BACKGROUND: Artificial intelligence (AI) -based, mammography breast cancer (bc) risk prediction models show improved discriminatory accuracy relative to clinical risk models. However, data on their calibration are limited. This study compared model performance of three clinical bc risk models-Gail, Tyrer-Cuzick (TC) v8, and Breast Cancer Surveillance Consortium (BCSC) v3 - to the MIRAI AI-risk model. METHODS: Digital mammograms were ascertained from a screening mammography cohort of 12,308 women within the Mayo Clinic Biobank with 250 incident BCs (176 invasive) within five years. We predicted five-year bc risk, estimated discriminatory accuracy (concordance [C]-index) and calibration (observed to expected ratio [O/E]) of both overall and invasive bc, and compared estimates using bootstrapping approaches. RESULTS: MIRAI demonstrated similar or improved discriminatory accuracy of overall bc (C-index = 0.71, 95% confidence interval [CI]=0.68-0.74) and invasive bc (C-index = 0.71, 95%CI = 0.67-0.75) compared to clinical models (Overall bc: C-index = 0.59-0.68, Invasive bc: C-index = 0.60-0.68). MIRAI's calibration for risk of overall bc (O/E = 0.96, 95%CI = 0.85-1.08) was improved compared to Gail (O/E = 1.22, 95%CI = 1.07-1.38) and BCSC (O/E = 1.38, 95%CI = 1.22-1.56) but similar to TC with volumetric percent density and polygenic risk score (O/E = 0.99, 95%CI = 0.87-1.13). However, for low-risk women (approximately 50%), MIRAI overestimated risk of overall bc. MIRAI also overestimated risk of invasive bc across the risk spectrum (O/E = 0.68, 95%CI = 0.58-0.78), while clinical models had good calibration (O/E = 0.86-0.99). CONCLUSION: MIRAI demonstrated stronger discriminatory accuracy than clinical models for five-year overall and invasive bc risk prediction but overestimated risk for both bc endpoints. AI-based risk models should consider discriminatory accuracy and calibration for invasive cancer before implementation.
Macy ME, Fox E, Weigel BJ
… +7 more, Foster JH, Beeles T, Sullivan MB, Towcimak N, Gore L, Smith MA, Hawkins DS
J Natl Cancer Inst
· 2026 Mar · PMID 41885402
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BACKGROUND: The Children's Oncology Group (COG), formed in 2000, is a large international trial network that has conducted over 330 clinical trials for pediatric, adolescent, and young adult cancers. The role of COG tria...BACKGROUND: The Children's Oncology Group (COG), formed in 2000, is a large international trial network that has conducted over 330 clinical trials for pediatric, adolescent, and young adult cancers. The role of COG trial data for Food and Drug Administration (FDA) approval of pediatric oncology indications was assessed since 2000. METHODS: All FDA approvals for pediatric oncology indications between January 1, 2000, and December 31, 2024, were reviewed. Data were collected from the FDA website, clinicaltrials.gov and COG database. RESULTS: Twenty-five (47%) of the 53 FDA pediatric indication approvals for 37 different drugs or biologics utilized COG clinical trial data for the approval of the pediatric indication. The 21 COG studies used for approvals were supported by three different partnership models, with 14 indications (26% of all pediatric approvals) supported by data from 15 trials utilizing the COG cooperative agreement award from the National Cancer Institute (NCI). CONCLUSION: Almost half of FDA approved pediatric indications for oncology therapeutics were supported by data from COG trials, highlighting the effectiveness of this public-private partnership model in producing the level of clinical evidence required for regulatory success.
Kwan ML, D'Addario L, Lee C
… +17 more, Roh JM, Ergas IJ, Shariff-Marco S, Cheng I, Von Behren J, Wu AH, Morey BN, Castillo E, Kim MO, Lin K, Loo LWM, Kurian A, Omilian AR, John EM, Yao S, Gomez SL, Kushi LH
J Natl Cancer Inst
· 2026 Mar · PMID 41883257
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BACKGROUND: In the US, Asian American females with breast cancer have better survival than other groups, and survival differs across Asian American ethnicities. Reasons remain unclear. METHODS: We compared the survival o...BACKGROUND: In the US, Asian American females with breast cancer have better survival than other groups, and survival differs across Asian American ethnicities. Reasons remain unclear. METHODS: We compared the survival of 5294 Asian American ethnicities and 5294 non-Latina White (NLW) females with incident stage I-IV breast cancer (2000-2015) in Kaiser Permanente Northern California. With follow-up through December 31, 2020, survival analysis was conducted using cause-specific Cox proportional hazards models adjusting for sociodemographic, clinical, treatment, social environment, and lifestyle factors. Overall, 1048 deaths (581 breast cancer-related) occurred in Asian American females and 1673 deaths (779 breast cancer-related) in NLW females. RESULTS: Compared with NLW females, Asian American females were younger (median = 56.2 vs. 63.0 years), lived in the highest socioeconomic status neighborhoods (Quintiles 4/5 = 57.7% vs. 50.3%), had fewer comorbidities (45.2% vs. 35.9% with zero), had a lower body mass index (BMI) (median = 24.8 vs. 27.4 kg/m2), and never smoked (47.2% vs. 26.9%), varying by Asian American ethnicity. All-cause mortality was lower in Asian American than NLW females (hazard ratio [HR] = 0.82; 95% CI = 0.74 to 0.91). Chinese (HR = 0.84; 95% CI = 0.70 to 1.00), Japanese (HR = 0.69; 95% CI = 0.55 to 0.88), and South Asian (HR = 0.73; 95% CI = 0.53 to 0.99) females had persistent survival advantages over NLW females. Adjusting for BMI and smoking attenuated associations. For breast cancer-specific mortality, associations were similar, though statistically non-significant. CONCLUSIONS: Asian American females-especially those of Chinese, Japanese, and South Asian descent-had better survival than non-Latina NLW females. Disaggregating Asian American ethnicities clarifies survival differences and may inform research on personal, social, and lifestyle factors to benefit all patients.
J Natl Cancer Inst
· 2026 May · PMID 41883186
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We calculated age-standardized cervical cancer incidence rates and trends by histologic type among women aged 15-29 years, using cancer registry data covering approximately 99% of the US population. We examined differenc...We calculated age-standardized cervical cancer incidence rates and trends by histologic type among women aged 15-29 years, using cancer registry data covering approximately 99% of the US population. We examined differences in incidence rates from the earliest to the most recent study period and quantified changes over time using joinpoint regression. Incidence rates for cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) decreased significantly during 1999-2022 in all age groups (15-20, 21-24, 25-29 years). Among women aged 15-20 years, cervical SCC rates were stable from 1999 to 2010 but declined substantially by 24.2% (95% confidence interval = -44.4 to -18.0) each year from 2010 to 2022, with only a few cases reported during 2017-2022. These findings show that cervical cancer incidence has declined among adolescents and young adult women in the United States, particularly in more recent years, highlighting the population-level impact of cervical cancer prevention measures.