Rhoikos Furtwängler,Rana Dandis,Harm van Tinteren,Nils Welter,Christian Vokuhl,Gordan Vujanic,Aurore Coulomb-L'Hermine,Jan Godzinski,Jens-Peter Schenk,Hervé Brisse,Manfred Gessler,Leo Kager,Patrick Melchior,Steven W Warmann,Arnauld Verschuur,Beatriz de Camargo,Gema Ramirez-Villar,Filippo Spreafico,Jesper Brok,Tanzina Chowdhury,Marry M van den Heuvel-Eibrink,Norbert Graf
PURPOSEThe International Society of Paediatric Oncology-Renal Tumour Study Group (SIOP-RTSG) classifies blastemal-type Wilms tumor (WT) after preoperative chemotherapy as high-risk (HRWT). It remains unresolved whether residual absolute volume of blastema (AVB) functions as an independent prognostic factor across WT subtypes.MATERIALS AND METHODSAVB was calculated from preoperative tumor volume, necrosis percentage, and viable blastema using prospectively collected data from 3,459 patients with unilateral WT treated in the SIOP WT 2001 study between 2001 and 2018. Martingale residual plots defined AVB thresholds discriminating survival in localized HRWT, intermediate-/low-risk WT (IRWT/LRWT), and metastatic WT (stage IV). Complete AVB data were available for 1,802 patients (51.2%); 298 (16.5%) had stage IV disease. Of 1,504 patients with localized WT, 265 (17.6%) had HRWT, 1,203 (79.9%) had IRWT, and 36 (2.4%) had LRWT.RESULTSMultivariable Cox regression adjusted for age, sex, and local stage confirmed significantly worse survival for patients exceeding these AVB thresholds: (1) IRWT (≥20 mL): Hazard ratio for event-free survival (EFS) 2.93 (95% CI, 2.08 to 4.12) and overall survival (OS) 2.76 (95% CI, 1.32 to 5.77); (2) HRWT (≥100 mL): EFS 2.89 (95% CI, 1.59 to 5.26) and OS 3.25 (95% CI, 1.45 to 7.27); and (3) stage IV (≥10 mL): EFS 5.78 (95% CI, 3.65 to 9.17) and OS 4.59 (95% CI, 2.57 to 8.17). Patients above these thresholds had significantly lower 2-year EFS (P < .0001). In stage II to III IRWT patients with AVB ≥20 mL, those treated with doxorubicin had superior EFS versus those without (87.6%, 95% CI, 81.5 to 94.1 v 69.2%, 95% CI, 59.8 to 80.1; P = .0064).CONCLUSIONAVB after preoperative chemotherapy is a strong, independent predictor of both EFS and OS in WT across risk groups. An AVB of ≥20 mL identifies a clinically relevant subset of patients with IRWT who may benefit from intensified therapy with doxorubicin. These findings support the use of AVB as a stratification criterion in future SIOP-RTSG protocols.
{"title":"Residual Absolute Volume of Blastema as a Predictor of Clinical Outcomes in Patients With Wilms Tumor: A Report From the SIOP WT 2001 Study.","authors":"Rhoikos Furtwängler,Rana Dandis,Harm van Tinteren,Nils Welter,Christian Vokuhl,Gordan Vujanic,Aurore Coulomb-L'Hermine,Jan Godzinski,Jens-Peter Schenk,Hervé Brisse,Manfred Gessler,Leo Kager,Patrick Melchior,Steven W Warmann,Arnauld Verschuur,Beatriz de Camargo,Gema Ramirez-Villar,Filippo Spreafico,Jesper Brok,Tanzina Chowdhury,Marry M van den Heuvel-Eibrink,Norbert Graf","doi":"10.1200/jco-25-01755","DOIUrl":"https://doi.org/10.1200/jco-25-01755","url":null,"abstract":"PURPOSEThe International Society of Paediatric Oncology-Renal Tumour Study Group (SIOP-RTSG) classifies blastemal-type Wilms tumor (WT) after preoperative chemotherapy as high-risk (HRWT). It remains unresolved whether residual absolute volume of blastema (AVB) functions as an independent prognostic factor across WT subtypes.MATERIALS AND METHODSAVB was calculated from preoperative tumor volume, necrosis percentage, and viable blastema using prospectively collected data from 3,459 patients with unilateral WT treated in the SIOP WT 2001 study between 2001 and 2018. Martingale residual plots defined AVB thresholds discriminating survival in localized HRWT, intermediate-/low-risk WT (IRWT/LRWT), and metastatic WT (stage IV). Complete AVB data were available for 1,802 patients (51.2%); 298 (16.5%) had stage IV disease. Of 1,504 patients with localized WT, 265 (17.6%) had HRWT, 1,203 (79.9%) had IRWT, and 36 (2.4%) had LRWT.RESULTSMultivariable Cox regression adjusted for age, sex, and local stage confirmed significantly worse survival for patients exceeding these AVB thresholds: (1) IRWT (≥20 mL): Hazard ratio for event-free survival (EFS) 2.93 (95% CI, 2.08 to 4.12) and overall survival (OS) 2.76 (95% CI, 1.32 to 5.77); (2) HRWT (≥100 mL): EFS 2.89 (95% CI, 1.59 to 5.26) and OS 3.25 (95% CI, 1.45 to 7.27); and (3) stage IV (≥10 mL): EFS 5.78 (95% CI, 3.65 to 9.17) and OS 4.59 (95% CI, 2.57 to 8.17). Patients above these thresholds had significantly lower 2-year EFS (P < .0001). In stage II to III IRWT patients with AVB ≥20 mL, those treated with doxorubicin had superior EFS versus those without (87.6%, 95% CI, 81.5 to 94.1 v 69.2%, 95% CI, 59.8 to 80.1; P = .0064).CONCLUSIONAVB after preoperative chemotherapy is a strong, independent predictor of both EFS and OS in WT across risk groups. An AVB of ≥20 mL identifies a clinically relevant subset of patients with IRWT who may benefit from intensified therapy with doxorubicin. These findings support the use of AVB as a stratification criterion in future SIOP-RTSG protocols.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"9 1","pages":"JCO2501755"},"PeriodicalIF":45.3,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lisa Licitra,Makoto Tahara,Kevin Harrington,Mivael Olivera Hurtado de Mendoza,Ye Guo,Sercan Aksoy,Meiyu Fang,Tibor Csőszi,Mikhail Klochikhin,Thiago Bueno de Oliveira,Shunji Takahashi,Muh-Hwa Yang,Paul L Swiecicki,Caroline Even,Jérome Fayette,Corina Dutcus,Chinyere E Okpara,Juan Shen,Kimberly Benjamin,Burak Gumuscu,Robert I Haddad,
PURPOSEThe PD-1 inhibitor pembrolizumab is approved as first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In LEAP-010 (ClinicalTrials.gov identifier: NCT04199104), the multikinase inhibitor lenvatinib plus pembrolizumab was evaluated as first-line therapy in participants with PD-L1 combined positive score (CPS) ≥1 R/M HNSCC.METHODSIn this phase III, randomized, placebo-controlled, double-blind study, participants 18 years and older with PD-L1 CPS ≥1 R/M HNSCC deemed incurable by local therapy were randomly assigned 1:1 to lenvatinib 20 mg plus pembrolizumab 200 mg IV once every 3 weeks for ≤35 cycles or placebo orally once daily plus pembrolizumab 200 mg IV once every 3 weeks for ≤35 cycles. Primary end points were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Per the prespecified analysis plan, ORR and PFS were reported from the first interim analysis (IA1; data cutoff: July 6, 2022), and OS from IA2 (data cutoff: May 30, 2023).RESULTSFive hundred eleven participants were randomly assigned to lenvatinib plus pembrolizumab (n = 256) or placebo plus pembrolizumab (n = 255). The median time from random assignment to data cutoff was 11.5 months for IA1 and 21.3 months for IA2. At IA1, the median PFS was 6.2 months for lenvatinib plus pembrolizumab versus 2.8 months for placebo plus pembrolizumab (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.81]; P = .0001040); the ORR was 46.1% versus 25.4%, respectively (difference = 20.2% [95% CI, 10.5 to 29.6]; P = .0000251). At IA2, the median OS was 15.0 months for lenvatinib plus pembrolizumab versus 17.9 months for placebo plus pembrolizumab (HR,1.15 [95% CI, 0.91 to 1.45]; P = .882). At IA2, 170 (66.9%) participants receiving lenvatinib plus pembrolizumab had grade 3-4 all-cause adverse events compared with 97 (38.3%) participants on placebo plus pembrolizumab.CONCLUSIONIn participants with PD-L1 CPS ≥1 R/M HNSCC, first-line lenvatinib plus pembrolizumab significantly improved ORR and PFS, but not OS, compared with placebo plus pembrolizumab. The safety profile was consistent with published data.
{"title":"Pembrolizumab With or Without Lenvatinib as First-Line Therapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Phase III LEAP-010 Study.","authors":"Lisa Licitra,Makoto Tahara,Kevin Harrington,Mivael Olivera Hurtado de Mendoza,Ye Guo,Sercan Aksoy,Meiyu Fang,Tibor Csőszi,Mikhail Klochikhin,Thiago Bueno de Oliveira,Shunji Takahashi,Muh-Hwa Yang,Paul L Swiecicki,Caroline Even,Jérome Fayette,Corina Dutcus,Chinyere E Okpara,Juan Shen,Kimberly Benjamin,Burak Gumuscu,Robert I Haddad, ","doi":"10.1200/jco-25-00570","DOIUrl":"https://doi.org/10.1200/jco-25-00570","url":null,"abstract":"PURPOSEThe PD-1 inhibitor pembrolizumab is approved as first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In LEAP-010 (ClinicalTrials.gov identifier: NCT04199104), the multikinase inhibitor lenvatinib plus pembrolizumab was evaluated as first-line therapy in participants with PD-L1 combined positive score (CPS) ≥1 R/M HNSCC.METHODSIn this phase III, randomized, placebo-controlled, double-blind study, participants 18 years and older with PD-L1 CPS ≥1 R/M HNSCC deemed incurable by local therapy were randomly assigned 1:1 to lenvatinib 20 mg plus pembrolizumab 200 mg IV once every 3 weeks for ≤35 cycles or placebo orally once daily plus pembrolizumab 200 mg IV once every 3 weeks for ≤35 cycles. Primary end points were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Per the prespecified analysis plan, ORR and PFS were reported from the first interim analysis (IA1; data cutoff: July 6, 2022), and OS from IA2 (data cutoff: May 30, 2023).RESULTSFive hundred eleven participants were randomly assigned to lenvatinib plus pembrolizumab (n = 256) or placebo plus pembrolizumab (n = 255). The median time from random assignment to data cutoff was 11.5 months for IA1 and 21.3 months for IA2. At IA1, the median PFS was 6.2 months for lenvatinib plus pembrolizumab versus 2.8 months for placebo plus pembrolizumab (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.81]; P = .0001040); the ORR was 46.1% versus 25.4%, respectively (difference = 20.2% [95% CI, 10.5 to 29.6]; P = .0000251). At IA2, the median OS was 15.0 months for lenvatinib plus pembrolizumab versus 17.9 months for placebo plus pembrolizumab (HR,1.15 [95% CI, 0.91 to 1.45]; P = .882). At IA2, 170 (66.9%) participants receiving lenvatinib plus pembrolizumab had grade 3-4 all-cause adverse events compared with 97 (38.3%) participants on placebo plus pembrolizumab.CONCLUSIONIn participants with PD-L1 CPS ≥1 R/M HNSCC, first-line lenvatinib plus pembrolizumab significantly improved ORR and PFS, but not OS, compared with placebo plus pembrolizumab. The safety profile was consistent with published data.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"234 1","pages":"JCO2500570"},"PeriodicalIF":45.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Constance A Owens,Ethan B Ludmir,Qi Liu,Weiyu Qiu,Aashish C Gupta,Susan A Smith,Bastien Rigaud,Kristy K Brock,James E Bates,Taylor G Meyers,Arnold C Paulino,Christine B Peterson,Stephen F Kry,Jop C Teepen,Cecile M Ronckers,Joseph P Neglia,Wendy M Leisenring,Kevin C Oeffinger,Paul C Nathan,Lucie M Turcotte,David C Hodgson,Melissa M Hudson,Leslie L Robison,Chaya S Moskowitz,Gregory T Armstrong,Tara O Henderson,Yutaka Yasui,Rebecca M Howell
{"title":"Reply to: Methodologic Considerations for Subsequent Colorectal Cancer in Survivors of Childhood Cancer.","authors":"Constance A Owens,Ethan B Ludmir,Qi Liu,Weiyu Qiu,Aashish C Gupta,Susan A Smith,Bastien Rigaud,Kristy K Brock,James E Bates,Taylor G Meyers,Arnold C Paulino,Christine B Peterson,Stephen F Kry,Jop C Teepen,Cecile M Ronckers,Joseph P Neglia,Wendy M Leisenring,Kevin C Oeffinger,Paul C Nathan,Lucie M Turcotte,David C Hodgson,Melissa M Hudson,Leslie L Robison,Chaya S Moskowitz,Gregory T Armstrong,Tara O Henderson,Yutaka Yasui,Rebecca M Howell","doi":"10.1200/jco-26-00051","DOIUrl":"https://doi.org/10.1200/jco-26-00051","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"28 1","pages":"JCO2600051"},"PeriodicalIF":45.3,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Methodologic Considerations for Subsequent Colorectal Cancer in Survivors of Childhood Cancer.","authors":"Yixin Liu,Yin Liu,Yongchang Wei","doi":"10.1200/jco-25-02569","DOIUrl":"https://doi.org/10.1200/jco-25-02569","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"186 3 1","pages":"JCO2502569"},"PeriodicalIF":45.3,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-10Epub Date: 2026-02-06DOI: 10.1200/JCO-26-00221
Jordi Remon, Tina Cascone, Solange Peters
{"title":"Erratum: BR.31 Trial: Adjuvant Durvalumab as the Third Contender in Resected Non-Small Cell Lung Cancer.","authors":"Jordi Remon, Tina Cascone, Solange Peters","doi":"10.1200/JCO-26-00221","DOIUrl":"10.1200/JCO-26-00221","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"723"},"PeriodicalIF":41.9,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-10Epub Date: 2026-02-04DOI: 10.1200/JCO-25-02579
Evanthia Galanis
{"title":"Integrated Molecular Diagnosis Paving the Way for Therapeutic Success in Recurrent Astrocytoma Treatment.","authors":"Evanthia Galanis","doi":"10.1200/JCO-25-02579","DOIUrl":"10.1200/JCO-25-02579","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"622-625"},"PeriodicalIF":41.9,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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