{"doi":"10.1001/jama.2026.1929","title":"Tumor Debulking in Combination With Chemotherapy in Multiorgan Metastatic Colorectal Cancer","abstract":"<jats:sec>\n                    <jats:title>Importance</jats:title>\n                    <jats:p>Local therapy, including surgery, radiation, and ablation, is increasingly used in patients with multiorgan metastatic colorectal cancer (mCRC). However, prospective evidence for a survival benefit of tumor debulking is lacking.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective</jats:title>\n                    <jats:p>To investigate whether tumor debulking added to palliative chemotherapy improves survival of patients with multiorgan mCRC.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants</jats:title>\n                    <jats:p>This investigator-initiated, open-label, multicenter, randomized clinical trial enrolled patients with multiorgan mCRC between May 2013 and May 2023. The last date of follow-up was April 4, 2024. Patients were enrolled in 27 hospitals in the Netherlands and 1 in the UK. Adult patients with multiorgan mCRC were considered eligible if more than 80% tumor debulking was deemed feasible by resection, radiotherapy, and/or thermal ablation prior to starting first-line palliative chemotherapy.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions</jats:title>\n                    <jats:p>After achieving objective tumor response or stable disease after 3 cycles of capecitabine and oxaliplatin or 4 cycles of 5-fluorouracil and oxaliplatin with or without bevacizumab, patients were randomized 1:1 to receive chemotherapy alone (standard care group) or tumor debulking followed by chemotherapy.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes and Measures</jats:title>\n                    <jats:p>The primary end point was overall survival. Secondary end points included progression-free survival and serious adverse events. These outcomes were analyzed in the intention-to-treat population, applicable from randomization. A prespecified interim analysis performed after the initial 100 participants were enrolled revealed that the trial was both safe and feasible to proceed.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>\n                      A total of 382 of 454 enrolled patients were randomized: 192 in the chemotherapy alone group (133 [69%] male) and 190 in the chemotherapy plus tumor debulking group (127 [67%] male). The median age was 64 years in both groups. After a median follow-up of 32.3 months, median overall survival in the chemotherapy alone group was 27.5 months vs 30.0 months in the chemotherapy plus tumor debulking group (adjusted hazard ratio, 0.88 [95% CI, 0.70-1.10];\n                      <jats:italic>P</jats:italic>\n                       = .26). Median progression-free survival in the chemotherapy alone group was 10.4 months vs 10.5 months in the chemotherapy plus tumor debulking group (adjusted hazard ratio, 0.83 [95% CI, 0.67-1.02];\n                      <jats:italic>P</jats:italic>\n                       = .08). More patients in the chemotherapy plus tumor debulking vs chemotherapy alone group had any serious adverse events (101 [53%] vs 74 [39%];\n                      <jats:italic>P</jats:italic>\n                       = .006).\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance</jats:title>\n                    <jats:p>Tumor debulking in addition to first-line palliative systemic treatment failed to improve overall survival compared with systemic treatment alone for patients with multiorgan mCRC and should not be considered standard care.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration</jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT01792934\">NCT01792934</jats:ext-link>\n                    </jats:p>\n                  </jats:sec>","journal":"JAMA","year":2026,"id":602056,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1543905,"name":"Lotte Bakkerus","orcid":null,"position":1,"is_corresponding":false},{"id":1543906,"name":"Anviti A. Adhin","orcid":null,"position":2,"is_corresponding":false},{"id":1543907,"name":"Barbara M. Zonderhuis","orcid":null,"position":3,"is_corresponding":false},{"id":1543908,"name":"Kathelijn S. Versteeg","orcid":null,"position":4,"is_corresponding":false},{"id":717192,"name":"Jurriaan B. Tuynman","orcid":"0000-0001-5952-8000","position":5,"is_corresponding":false},{"id":1543909,"name":"Martijn R. Meijerink","orcid":null,"position":6,"is_corresponding":false},{"id":1543911,"name":"Cornelis J. A. Haasbeek","orcid":null,"position":7,"is_corresponding":false},{"id":1543913,"name":"Johannes H. W. de Wilt","orcid":null,"position":8,"is_corresponding":false},{"id":1543914,"name":"Dirk J. Grunhagen","orcid":null,"position":9,"is_corresponding":false},{"id":1543915,"name":"Ewoud J. Smit","orcid":null,"position":10,"is_corresponding":false},{"id":1543916,"name":"John M. Primrose","orcid":null,"position":11,"is_corresponding":false},{"id":554683,"name":"John Bridgewater","orcid":"0000-0001-9186-1604","position":12,"is_corresponding":false},{"id":1543917,"name":"Esther van Meerten","orcid":null,"position":13,"is_corresponding":false},{"id":1543918,"name":"Jan-Willem B. de Groot","orcid":null,"position":14,"is_corresponding":false},{"id":1543919,"name":"Mathijs P. Hendriks","orcid":null,"position":15,"is_corresponding":false},{"id":1543920,"name":"Esther Oomen-de Hoop","orcid":null,"position":16,"is_corresponding":false},{"id":1435498,"name":"Tineke E. Buffart","orcid":"0000-0003-2464-7741","position":17,"is_corresponding":false},{"id":821501,"name":"Cornelis Verhoef","orcid":"0000-0001-9980-8613","position":18,"is_corresponding":false},{"id":1543921,"name":"Henk M. W. Verheul","orcid":null,"position":19,"is_corresponding":false},{"id":322475,"name":"Aart Beeker","orcid":"0000-0003-4133-769X","position":21,"is_corresponding":false},{"id":1543922,"name":"Laurens V Beerepoot","orcid":null,"position":22,"is_corresponding":false},{"id":1543923,"name":"Haiko J Bloemendal","orcid":null,"position":23,"is_corresponding":false},{"id":1543924,"name":"Daan Ten Bokkel Huinink","orcid":null,"position":24,"is_corresponding":false},{"id":1543925,"name":"Joyce M van Dodewaard-de Jong","orcid":null,"position":25,"is_corresponding":false},{"id":1543926,"name":"Cecile Grootscholten","orcid":null,"position":26,"is_corresponding":false},{"id":1543927,"name":"Brigitte Haberkorn","orcid":null,"position":27,"is_corresponding":false},{"id":1543928,"name":"Henk van Halteren","orcid":null,"position":28,"is_corresponding":false},{"id":1543929,"name":"Paul Hamberg","orcid":null,"position":29,"is_corresponding":false},{"id":1543930,"name":"Helgi H Helgason","orcid":null,"position":30,"is_corresponding":false},{"id":324477,"name":"Ronald Hoekstra","orcid":null,"position":31,"is_corresponding":false},{"id":1543931,"name":"Roel Hompes","orcid":null,"position":32,"is_corresponding":false},{"id":1543932,"name":"Geke AP Hospers","orcid":null,"position":33,"is_corresponding":false},{"id":1543933,"name":"Rob LH Jansen","orcid":null,"position":34,"is_corresponding":false},{"id":1543934,"name":"Frank JF Jeurissen","orcid":null,"position":35,"is_corresponding":false},{"id":1108924,"name":"Maartje Los","orcid":"0000-0002-4953-5271","position":36,"is_corresponding":false},{"id":1543935,"name":"Daniëlle Mathijssen-van Stein","orcid":null,"position":37,"is_corresponding":false},{"id":1543936,"name":"Leonie J Mekenkamp","orcid":null,"position":38,"is_corresponding":false},{"id":1543937,"name":"Hielke Meulenbeld","orcid":null,"position":39,"is_corresponding":false},{"id":1543938,"name":"Marco Polée","orcid":null,"position":40,"is_corresponding":false},{"id":1543939,"name":"Johannes FM Pruijt","orcid":null,"position":41,"is_corresponding":false},{"id":1543940,"name":"Mirte M Streppel","orcid":null,"position":42,"is_corresponding":false},{"id":1543941,"name":"Pieter J Tanis","orcid":null,"position":43,"is_corresponding":false},{"id":1543942,"name":"Frederiek Terheggen","orcid":null,"position":44,"is_corresponding":false},{"id":1543943,"name":"Jetske M Meerum Terwogt","orcid":null,"position":45,"is_corresponding":false},{"id":1543944,"name":"Hans Torrenga","orcid":null,"position":46,"is_corresponding":false},{"id":1543945,"name":"Monique M Troost","orcid":null,"position":47,"is_corresponding":false},{"id":1543946,"name":"Marija Trajkovic-Vidakovic","orcid":null,"position":48,"is_corresponding":false},{"id":1543947,"name":"Maarten Vermaas","orcid":null,"position":49,"is_corresponding":false},{"id":1543948,"name":"Marije M Vleugel","orcid":null,"position":50,"is_corresponding":false},{"id":1543949,"name":"Gerard Vreugdenhil","orcid":null,"position":51,"is_corresponding":false},{"id":1543950,"name":"Annette A van Zweeden","orcid":null,"position":52,"is_corresponding":false},{"id":1543904,"name":"Elske C. Gootjes","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Tumor Debulking in Combination With Chemotherapy in Multiorgan Metastatic Colorectal Cancer","abstract":"<jats:sec>\n                    <jats:title>Importance</jats:title>\n                    <jats:p>Local therapy, including surgery, radiation, and ablation, is increasingly used in patients with multiorgan metastatic colorectal cancer (mCRC). However, prospective evidence for a survival benefit of tumor debulking is lacking.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective</jats:title>\n                    <jats:p>To investigate whether tumor debulking added to palliative chemotherapy improves survival of patients with multiorgan mCRC.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants</jats:title>\n                    <jats:p>This investigator-initiated, open-label, multicenter, randomized clinical trial enrolled patients with multiorgan mCRC between May 2013 and May 2023. The last date of follow-up was April 4, 2024. Patients were enrolled in 27 hospitals in the Netherlands and 1 in the UK. Adult patients with multiorgan mCRC were considered eligible if more than 80% tumor debulking was deemed feasible by resection, radiotherapy, and/or thermal ablation prior to starting first-line palliative chemotherapy.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions</jats:title>\n                    <jats:p>After achieving objective tumor response or stable disease after 3 cycles of capecitabine and oxaliplatin or 4 cycles of 5-fluorouracil and oxaliplatin with or without bevacizumab, patients were randomized 1:1 to receive chemotherapy alone (standard care group) or tumor debulking followed by chemotherapy.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes and Measures</jats:title>\n                    <jats:p>The primary end point was overall survival. Secondary end points included progression-free survival and serious adverse events. These outcomes were analyzed in the intention-to-treat population, applicable from randomization. A prespecified interim analysis performed after the initial 100 participants were enrolled revealed that the trial was both safe and feasible to proceed.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>\n                      A total of 382 of 454 enrolled patients were randomized: 192 in the chemotherapy alone group (133 [69%] male) and 190 in the chemotherapy plus tumor debulking group (127 [67%] male). The median age was 64 years in both groups. After a median follow-up of 32.3 months, median overall survival in the chemotherapy alone group was 27.5 months vs 30.0 months in the chemotherapy plus tumor debulking group (adjusted hazard ratio, 0.88 [95% CI, 0.70-1.10];\n                      <jats:italic>P</jats:italic>\n                       = .26). Median progression-free survival in the chemotherapy alone group was 10.4 months vs 10.5 months in the chemotherapy plus tumor debulking group (adjusted hazard ratio, 0.83 [95% CI, 0.67-1.02];\n                      <jats:italic>P</jats:italic>\n                       = .08). More patients in the chemotherapy plus tumor debulking vs chemotherapy alone group had any serious adverse events (101 [53%] vs 74 [39%];\n                      <jats:italic>P</jats:italic>\n                       = .006).\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance</jats:title>\n                    <jats:p>Tumor debulking in addition to first-line palliative systemic treatment failed to improve overall survival compared with systemic treatment alone for patients with multiorgan mCRC and should not be considered standard care.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration</jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT01792934\">NCT01792934</jats:ext-link>\n                    </jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41837962","pmcid":null,"openalex_id":"https://openalex.org/W7137222038","authors":[],"funders":[],"total_grants":0,"fwci":43.0146,"citation_percentile":0.99836694,"influential_citations":0,"citation_trend":[{"year":2026,"count":8}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12993731/","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12993731/","host_type":"repository"},{"url":"https://jamanetwork.com/journals/jama/articlepdf/2846530/jama_gootjes_2026_oi_260007_1776090320.88234.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1001/jama.2026.1929","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41837962","host_type":"repository"},{"url":"https://pure.eur.nl/en/publications/0466e458-b7fb-492f-990e-432789e11d6e","host_type":"repository"},{"url":"https://hdl.handle.net/2066/331768","host_type":"repository"}],"fields_of_study":["Colorectal Cancer Treatments and Studies","Colorectal Cancer Surgical Treatments","Hepatocellular Carcinoma Treatment and Prognosis","Adult","Aged","Female","Humans","Male","Middle Aged","Antineoplastic Combined Chemotherapy Protocols","Bevacizumab","Capecitabine","Colorectal Neoplasms","Cytoreduction Surgical Procedures","Fluorouracil","Oxaliplatin","Palliative Care","Chemotherapy, Adjuvant","Ablation Techniques","Follow-Up Studies","Progression-Free Survival","Young Adult"],"mesh_terms":["Bevacizumab","Capecitabine","Oxaliplatin","Progression-Free Survival","Adult","Aged","Antineoplastic Combined Chemotherapy Protocols","Female","Fluorouracil","Follow-Up Studies","Humans","Male","Middle Aged","Palliative Care","Colorectal Neoplasms","Chemotherapy, Adjuvant","Ablation Techniques","Young Adult","Cytoreduction Surgical Procedures"],"keywords":["Debulking","Oxaliplatin","Colorectal cancer","Clinical endpoint","Chemotherapy","Tumor Debulking","Capecitabine","Palliative care","Progression-free survival"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T18:10:38.311272Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}