Raimondi A, Tinè G, Boige V
… +16 more, Ballhausen A, Gourgou S, Stahler A, Randon G, Manca P, Brument E, Alig AHS, Morano F, Prisciandaro M, Ambrosini M, Fazio R, Zhu Y, Miceli R, Bouche O, Modest DP, Pietrantonio F
J Natl Cancer Inst
· 2026 May · PMID 42178223
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BACKGROUND: Doublet chemotherapy plus anti-EGFR is a standard of care in left-sided, microsatellite stable, RAS/BRAF wt (wt) mCRC. Guidelines recommend treatment de-escalation after achieving disease control with inducti...BACKGROUND: Doublet chemotherapy plus anti-EGFR is a standard of care in left-sided, microsatellite stable, RAS/BRAF wt (wt) mCRC. Guidelines recommend treatment de-escalation after achieving disease control with induction. Maintenance and intermittent (stop&go) strategies were investigated but not directly compared. METHODS: We performed an individual patient data pooled analysis of three randomized phase II trials (PanaMa, Valentino, PRODIGE-28 TIME), focused on toxicity analysis. Only patients with left-sided, non-MSI-H, RAS/BRAF V600E wt who started protocol-planned post-induction were included and stratified into three treatment groups: 5-FU/LV plus anti-EGFR maintenance, anti-EGFR alone, stop&go. Longitudinal toxicity data were collected and analyzed according to literature-based approach (Toxicity over Time; ToxT), incorporating dimension of time into adverse event (AE) assessment and analyzing individual and groups of AEs comparing treatment groups. RESULTS: Overall, 327 patients were included: 166, 109 and 52 patients received anti-EGFR plus 5-FU/LV maintenance, anti-EGFR alone and stop&go, respectively. Mean AE grades for chemotherapy-related toxicity showed different longitudinal patterns. Mean Grades in stop&go were lower in early cycles and increased later, higher values were reported for combination maintenance. Considering anti-EGFR-related skin toxicity, the mean AE grade was constantly lower for stop&go compared to maintenance groups. Overall, grade 3/4 AEs were more represented in maintenance groups versus stop&go, although the predominant grade was 1 across cycles for all groups. CONCLUSIONS: In our IPD analysis, indirectly comparing three clinical trials, stop&go showed lower anti-EGFR skin-related toxicity versus maintenance. Shared decision-making, considering patient and tumor features and treatment tolerability, may allow defining optimal de-intensification strategy.
Wong ML, Lee MK, Kour O
… +10 more, Satele D, Presley CJ, Le-Rademacher J, Ojelabi M, Chow S, Stinchcombe TE, Homan S, Finnes HD, Waqar S, Jatoi A
J Natl Cancer Inst
· 2026 May · PMID 42161344
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BACKGROUND: Older adults remain underrepresented in prospective trials of immunotherapy for advanced lung cancer. To estimate pembrolizumab adverse events (AE), we conducted a multicenter, nonrandomized open-label phase...BACKGROUND: Older adults remain underrepresented in prospective trials of immunotherapy for advanced lung cancer. To estimate pembrolizumab adverse events (AE), we conducted a multicenter, nonrandomized open-label phase II trial of oncologist-choice first-line pembrolizumab ± chemotherapy for older adults with advanced lung adenocarcinoma. METHODS: Alliance A171901 enrolled patients aged ≥70 years with stage IV or recurrent lung adenocarcinoma starting oncologist-choice of first-line pembrolizumab ± carboplatin and pemetrexed. The primary endpoint was the proportion of patients experiencing a solicited grade ≥3 AE within six months. Secondary endpoints included overall survival (OS), quality of life (QOL), and association of a geriatric assessment toxicity risk score with severe AEs. RESULTS: Among 95 evaluable patients, 43 (45.2%) received pembrolizumab and 52 (54.7%) received pembrolizumab plus chemotherapy. Median age was 77 years; 11.6% had an Eastern Cooperative Oncology Group performance status ≥2. During six months of treatment, 25.6% (95% CI 13.5 to 41.2%) experienced a solicited grade ≥3 AE in the monotherapy group and 42.3% (95% CI 28.7 to 56.8%) in the combination group. Median OS was 16.4 months (95% CI 10.1-not estimable) with monotherapy and 29.9 months (95% CI 16.4-not estimable) with combination therapy. QOL worsened during treatment. The geriatric assessment toxicity risk score was not associated with severe AEs with pembrolizumab ± chemotherapy. CONCLUSIONS: Older adults with advanced lung adenocarcinoma receiving pembrolizumab ± chemotherapy had comparable AE rates to those in prior registration trials that excluded frail patients. These findings can inform shared decision making and support inclusion of older adults in future trials. CLINICAL TRIAL: NCT04533451.
Nader-Marta G, Zheng Y, Rosenberg SM
… +16 more, Dibble KE, Mayer EL, Poorvu PD, Ruddy KJ, Guzman-Arocho YD, Collins LC, Peppercorn J, Schapira L, Valenza C, Borges VF, Tayob N, Come SE, Warner E, Polyak K, Winer EP, Partridge AH
J Natl Cancer Inst
· 2026 May · PMID 42152224
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BACKGROUND: Breast cancer (bc) diagnosed during pregnancy or postpartum often presents with aggressive features, potentially influenced by hormonal, immunologic, and tissue remodeling changes. Studies have suggested that...BACKGROUND: Breast cancer (bc) diagnosed during pregnancy or postpartum often presents with aggressive features, potentially influenced by hormonal, immunologic, and tissue remodeling changes. Studies have suggested that postpartum bc may be associated with worse outcomes, though most evidence is retrospective and constrained by methodological limitations. This study evaluated associations between pregnancy history, recency of childbirth, and long-term outcomes in a prospective cohort of young patients with early-stage bc. PATIENTS AND METHODS: Patients aged ≤40 years with stage I-III bc enrolled in the Young Women's Breast Cancer Study were categorized at diagnosis as nulligravid, nulliparous, pregnant, or parous (≤5 vs 5 to 10 years postpartum). Analyses were stratified by bc subtype [estrogen receptor-positive [ER+]/HER2-, HER2+, and triple-negative (TNBC)], with distant recurrence-free survival (DRFS) as the primary endpoint. RESULTS: Among 859 patients, 257 (29.9%) were nulligravid, 50 (5.8%) nulliparous, 37 (4.3%) pregnant, and 515 (60.0%) parous. Pregnant patients had proportionally more TNBC, nodal involvement, T3/T4, and grade 3 tumors. After 11.1 years median follow-up, pregnancy or postpartum status was not independently associated with DRFS in multivariable models adjusted for age, tumor characteristics, and treatment, with consistent findings across ER+/HER2-, HER2+, and TNBC subtypes. Sensitivity analyses, including further categorization of postpartum diagnoses (<2 vs 2 to 5 years), yielded consistent results. CONCLUSIONS: Pregnancy history and recency of childbirth were not independently associated with long-term DRFS. Despite more aggressive features at diagnosis, patients diagnosed during or after pregnancy had comparable outcomes after adjustment, suggesting no adverse prognostic impact. CLINICAL TRIAL REGISTRATION: NCT01468246 (https://clinicaltrials.gov/study/NCT01468246?term=NCT01468246&rank=1).
Schwartz LF, Wesevich A, Englum BR
… +5 more, Damodharan S, Desai AV, Laetsch TW, Huo D, Henderson TO
J Natl Cancer Inst
· 2026 May · PMID 42149832
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BACKGROUND: We analyzed trends in survival of children and adolescents diagnosed with cancer in the United States from 1975 to 2022 using the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results...BACKGROUND: We analyzed trends in survival of children and adolescents diagnosed with cancer in the United States from 1975 to 2022 using the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) 8 and 17 databases. Our goal was to provide an updated overview of outcomes and highlight disparities to guide future research. METHODS: Data were obtained from the SEER 8 and 17 registries for patients diagnosed at 0 to 19 years. Overall survival (OS) was stratified by race/ethnicity, diagnosis, and population density. Temporal trends in five-year OS were evaluated using the NCI Joinpoint Regression Program. Kaplan-Meier survival curves with log-rank tests assessed survival differences across subgroups. Multivariable Cox proportional hazards models evaluated OS, adjusted for age, decade of diagnosis and race/ethnicity. RESULTS: A total of 52,165 patients were diagnosed with cancer in SEER 8, and 100,110 in SEER 17. Five-year OS for all cancers improved from 60% (95% CI:56 to 64%) in 1975 to 90% (95% CI : 88 to 91%) in 2017. Survival gains were greatest in acute lymphoblastic leukemia, with more modest improvements in solid tumors. Mortality beyond 20 years persisted for some cancers, including Hodgkin lymphoma. Survival differed significantly by race/ethnicity (p < 0.001), with non-Hispanic Black patients experiencing the lowest five-year OS across multiple cancers, even after adjusting for age/decade of diagnosis. CONCLUSIONS: Survival for childhood and adolescent cancers has markedly improved over the past five decades, yet progress remains uneven across cancer types and race/ethnicity. Understanding drivers of disparities is essential to achieve equitable outcomes for all young cancer patients.
Opperman T, Patel R, Chiong JD
… +2 more, Stewart DJ, Nasser A
J Natl Cancer Inst
· 2026 May · PMID 42109045
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In oncology trials, overall survival (OS) and progression-free survival (PFS) are typically summarized with Kaplan-Meier (KM) curves, but medians cannot be estimated when follow-up is early. We evaluated whether exponent...In oncology trials, overall survival (OS) and progression-free survival (PFS) are typically summarized with Kaplan-Meier (KM) curves, but medians cannot be estimated when follow-up is early. We evaluated whether exponential-decay regression applied to the earliest quartile of KM data could approximate mature medians. A total of 114 phase III immunotherapy trials encompassing 420 treatment arms were analyzed, yielding 618 evaluable survival curves across OS and PFS endpoints. For immunotherapy OS, predicted and reported medians showed no significant difference (P=.59; R2 = 0.76; concordance correlation coefficient = 0.87). For immunotherapy PFS, predictions modestly overestimated medians (P < .001; R2 = 0.50). Non-immunotherapy arms demonstrated overestimation for both OS (R2 = 0.61) and PFS (R2 = 0.68). Pooled OS performance was good (R2 = 0.70). Early exponential modeling may offer a transparent tool for interim OS estimation in immunotherapy trials, warranting prospective validation.
Dolatkhah R, Onyije FM, Bouaoun L
… +2 more, Olsson A, Schüz J
J Natl Cancer Inst
· 2026 May · PMID 42109041
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BACKGROUND: Given the limited evidence on causes of childhood lymphoma, this systematic review and meta-analysis synthesized data on suggested factors associated with the risk of Hodgkin's lymphoma (HL) and non-Hodgkin's...BACKGROUND: Given the limited evidence on causes of childhood lymphoma, this systematic review and meta-analysis synthesized data on suggested factors associated with the risk of Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). METHODS: PubMed, Web of Science, and Embase were searched for peer-reviewed studies. Eligible articles were appraised using Joanna Briggs Institute tools. Random-effects meta-analysis reported pooled effect sizes (ES) with 95% confidence intervals (CI), combining cohort and case-control studies' results as primary analysis. RESULTS: Sixty-one articles met the inclusion criteria. For HL, factors such as gestational age, gestational size, mode of delivery (caesarean), and birth order were assessed in only a few cohort articles, showing no associations. High birthweight (>4000 g) suggested increased HL risk (ES = 1.20, 1.02-1.41). Younger maternal age (≤25 years) showed no association in cohort studies but evidence of increased risk in case-control studies (ES = 1.81, 1.25-2.63). Maternal smoking (≥10 cig/day) showed no association, and parental occupational and household pesticide exposures were not associated with HL risk. For NHL, no consistent associations with perinatal factors were identified. Maternal smoking (ES ranging from 1.31-1.38) and paternal smoking (1 to 10 cig/day; ES = 1.56, 1.09-2.24) showed some evidence of increased risks. Household paternal pesticide exposure (ES = 1.74, 1.24-2.45) and maternal insecticide exposure (ES = 1.97, 1.42-2.73) were also associated with increased risks. CONCLUSION: A modest number of eligible articles for most potential risk factors resulted in limited evidence and shows the need for more aetiological studies in international collaborations.
Rizwan A, Divi R, Ossandon MR
… +2 more, Harris LN, Sorg BS
J Natl Cancer Inst
· 2026 May · PMID 42108572
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The National Cancer Institute (NCI) convened a three-day virtual workshop, Transformative Microsystems for Cancer Diagnosis, Treatment Monitoring, and Clinical Integration (September 23-25, 2025). The meeting assembled e...The National Cancer Institute (NCI) convened a three-day virtual workshop, Transformative Microsystems for Cancer Diagnosis, Treatment Monitoring, and Clinical Integration (September 23-25, 2025). The meeting assembled experts from government, academia, and industry to discuss how microphysiological systems (MPS), tumor- and organ-on-a-chip devices, and integrated liquid-biopsy platforms are reshaping oncology. Sessions explored innovation, translational implementation, clinical usability, and policy barriers. This commentary outlines a roadmap for bridging biology, computation, and device design to transform microsystems from experimental tools into integrated components of personalized cancer care. The workshop consensus was that the next phase of innovation must focus on reproducibility, scalable and quality-controlled manufacturing, and clinical usability. FDA clearance alone does not guarantee patient access to microsystem diagnostics or improved outcomes, and early engagement with payers is essential to ensure validated technologies meet cost-effectiveness criteria for insurance coverage. Collaboration with end-users early in the design process is also essential as poor usability is a primary cause of product failure. Key barriers to clinical translation include a lack of consensus standards (e.g., leakage testing, flow-rate calibration, sensor validation) and availability of biobank materials for validating translational microsystem technologies.
Verkolf EMM, van Dam JL, Dekker EN
… +11 more, Janssen QP, Prakash LR, DeSilva A, de Wilde RF, Besselink MG, Wei AC, Zureikat AH, Katz MHG, Tzeng CD, Groot Koerkamp B, Trans-Atlantic Pancreatic Surgery (TAPS) Consortium
J Natl Cancer Inst
· 2026 Jun · PMID 42108563
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BACKGROUND: Neoadjuvant chemotherapy is increasingly used for patients with localized pancreatic ductal adenocarcinoma (PDAC), although the likelihood of subsequent resection remains uncertain. The aim of this study was...BACKGROUND: Neoadjuvant chemotherapy is increasingly used for patients with localized pancreatic ductal adenocarcinoma (PDAC), although the likelihood of subsequent resection remains uncertain. The aim of this study was to develop a prediction model using baseline characteristics to estimate the probability of meeting prespecified criteria for resection after induction FOLFIRINOX. METHODS: This retrospective study included patients with localized PDAC who received (m)FOLFIRINOX as initial treatment in 5 referral centers in the United States and the Netherlands (2012-2019). Multivariable logistic regression identified independent predictors of resection and was used to develop a prediction model. RESULTS: Among 1835 patients, 18.9% were classified as potentially resectable (PR), 28.9% as borderline resectable (BR), and 52.2% as locally advanced (LA). Observed resection rates were 70.5% for PR, 53.1% for BR, and 17.8% for LA PDAC. Unfavorable independent factors for resection were advanced anatomical stage (BR, OR = 0.51; 95% CI = 0.37 to 0.69 and LA, OR = 0.11; 95% CI = 0.08 to 0.15), baseline CA19-9 >500 U/mL (OR = 0.60; 95% CI = 0.46 to 0.77), a WHO performance status of ≥1 (OR = 0.41; 95% CI = 0.33 to 0.52), and tumor size on baseline imaging >40 mm (OR = 0.62; 95% CI = 0.48 to 0.80). Depending on these factors, the predicted probability of resection ranged from 6.7% to 81.7%. CONCLUSION: At diagnosis, the probability of resection after induction (m)FOLFIRINOX for localized PDAC ranged from 7% to 82%, depending on anatomical stage, CA19-9 level, performance status, and tumor size at baseline. This prediction model may help communicate realistic expectations for the probability of resection.