{"id":"https://openalex.org/W4362684563","doi":"https://doi.org/10.21037/tcr-23-192","title":"Combining immunotherapy and radiotherapy in hepatocellular carcinoma: the importance of irradiated tumor burden and the possible role of a low dose radiotherapy induction strategy","display_name":"Combining immunotherapy and radiotherapy in hepatocellular carcinoma: the importance of irradiated tumor burden and the possible role of a low dose radiotherapy induction strategy","publication_year":2023,"publication_date":"2023-04-01","ids":{"openalex":"https://openalex.org/W4362684563","doi":"https://doi.org/10.21037/tcr-23-192","pmid":"https://pubmed.ncbi.nlm.nih.gov/37180671","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/10174792"},"language":"en","primary_location":{"id":"doi:10.21037/tcr-23-192","doi":"https://doi.org/10.21037/tcr-23-192","is_oa":true,"landing_page_url":"https://doi.org/10.21037/tcr-23-192","pdf_url":"https://tcr.amegroups.com/article/viewFile/74022/pdf","source":{"id":"https://openalex.org/S2764965054","display_name":"Translational Cancer Research","issn_l":"2218-676X","issn":["2218-676X","2219-6803"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","poland-40","russia-white-list-4"],"host_organization":"https://openalex.org/P4310321814","host_organization_name":"AME Publishing Company","host_organization_lineage":["https://openalex.org/P4310321814"],"host_organization_lineage_names":["AME Publishing Company"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Translational Cancer Research","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"diamond","oa_url":"https://tcr.amegroups.com/article/viewFile/74022/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5072499473","display_name":"Clemens Grassberger","orcid":"https://orcid.org/0000-0002-4425-4489","observed_orcids":["https://orcid.org/0000-0002-4425-4489"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]},{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Clemens Grassberger","raw_affiliation_strings":["Department of Radiation Oncology, University of Washington, Seattle, WA, USA","Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, WA, USA","Research Associate Professor, Radiation Oncology, School of Medicine, UW Medicine, 1959 NE Pacific St., Box 356043, Seattle, WA 98195, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Radiation Oncology, University of Washington, Seattle, WA, USA","institution_ids":["https://openalex.org/I201448701"]},{"raw_affiliation_string":"Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, WA, USA","institution_ids":["https://openalex.org/I201448701","https://openalex.org/I4210089486"]},{"raw_affiliation_string":"Research Associate Professor, Radiation Oncology, School of Medicine, UW Medicine, 1959 NE Pacific St., Box 356043, Seattle, WA 98195, USA","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073989587","display_name":"Gentry Teng King","orcid":"https://orcid.org/0000-0002-7525-8802","observed_orcids":["https://orcid.org/0000-0002-7525-8802"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]},{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Gentry King","raw_affiliation_strings":["Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, WA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, WA, USA","institution_ids":["https://openalex.org/I201448701","https://openalex.org/I4210089486"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5018262026","display_name":"Smith Apisarnthanarax","orcid":"https://orcid.org/0000-0003-4522-8300","observed_orcids":["https://orcid.org/0000-0003-4522-8300"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Smith Apisarnthanarax","raw_affiliation_strings":["Department of Radiation Oncology, University of Washington, Seattle, WA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Radiation Oncology, University of Washington, Seattle, WA, USA","institution_ids":["https://openalex.org/I201448701"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5072499473"],"corresponding_institution_ids":["https://openalex.org/I201448701","https://openalex.org/I4210089486"],"apc_list":null,"apc_paid":null,"fwci":0.5018,"has_fulltext":true,"cited_by_count":3,"citation_normalized_percentile":{"value":0.6063033,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":96},"biblio":{"volume":"12","issue":"4","first_page":"701","last_page":"704"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10073","display_name":"Hepatocellular Carcinoma Treatment and Prognosis","score":0.836899995803833,"subfield":{"id":"https://openalex.org/subfields/2721","display_name":"Hepatology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10073","display_name":"Hepatocellular Carcinoma Treatment and Prognosis","score":0.836899995803833,"subfield":{"id":"https://openalex.org/subfields/2721","display_name":"Hepatology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.15809999406337738,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11395","display_name":"Radiopharmaceutical Chemistry and Applications","score":0.0008999999845400453,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/hepatocellular-carcinoma","display_name":"hepatocellular carcinoma","score":0.9980000257492065},{"id":"https://openalex.org/keywords/stereotactic-body-radiation-therapy","display_name":"stereotactic body radiotherapy","score":0.9580000042915344},{"id":"https://openalex.org/keywords/nivolumab","display_name":"nivolumab","score":0.8849999904632568},{"id":"https://openalex.org/keywords/ipilimumab","display_name":"ipilimumab","score":1.0},{"id":"https://openalex.org/keywords/immune-checkpoint-inhibitors","display_name":"immune checkpoint inhibitors","score":0.9279999732971191},{"id":"https://openalex.org/keywords/radiotherapy-immunotherapy-combination","display_name":"radiotherapy-immunotherapy combination","score":0.7279999852180481},{"id":"https://openalex.org/keywords/extrahepatic-metastases","display_name":"extrahepatic metastasis","score":0.7049999833106995},{"id":"https://openalex.org/keywords/trial-design","display_name":"trial design","score":0.35899999737739563},{"id":"https://openalex.org/keywords/overall-response-rate","display_name":"overall response rate","score":0.5360000133514404},{"id":"https://openalex.org/keywords/log-rank-test","display_name":"log-rank test","score":0.5249999761581421},{"id":"https://openalex.org/keywords/proportional-hazards-assumption","display_name":"proportional hazards assumption","score":0.5220000147819519},{"id":"https://openalex.org/keywords/treatment-related-toxicity","display_name":"treatment toxicity","score":0.42800000309944153}],"concepts":[{"id":"https://openalex.org/C2778019345","wikidata":"https://www.wikidata.org/wiki/Q1148337","display_name":"Hepatocellular carcinoma","level":2,"score":0.8639119863510132},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.8016091585159302},{"id":"https://openalex.org/C509974204","wikidata":"https://www.wikidata.org/wiki/Q180507","display_name":"Radiation therapy","level":2,"score":0.7198585271835327},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.6868040561676025},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.5562828183174133},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.43473076820373535},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.4311579763889313},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.1847403645515442}],"mesh":[],"locations_count":3,"locations":[{"id":"doi:10.21037/tcr-23-192","doi":"https://doi.org/10.21037/tcr-23-192","is_oa":true,"landing_page_url":"https://doi.org/10.21037/tcr-23-192","pdf_url":"https://tcr.amegroups.com/article/viewFile/74022/pdf","source":{"id":"https://openalex.org/S2764965054","display_name":"Translational Cancer Research","issn_l":"2218-676X","issn":["2218-676X","2219-6803"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","poland-40","russia-white-list-4"],"host_organization":"https://openalex.org/P4310321814","host_organization_name":"AME Publishing Company","host_organization_lineage":["https://openalex.org/P4310321814"],"host_organization_lineage_names":["AME Publishing Company"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Translational Cancer Research","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:10174792","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10174792","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10174792/pdf/tcr-12-04-701.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Transl Cancer Res","raw_type":"Text"},{"id":"pmid:37180671","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/37180671","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Translational cancer research","raw_type":"Editorial"}],"best_oa_location":{"id":"doi:10.21037/tcr-23-192","doi":"https://doi.org/10.21037/tcr-23-192","is_oa":true,"landing_page_url":"https://doi.org/10.21037/tcr-23-192","pdf_url":"https://tcr.amegroups.com/article/viewFile/74022/pdf","source":{"id":"https://openalex.org/S2764965054","display_name":"Translational Cancer Research","issn_l":"2218-676X","issn":["2218-676X","2219-6803"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","poland-40","russia-white-list-4"],"host_organization":"https://openalex.org/P4310321814","host_organization_name":"AME Publishing Company","host_organization_lineage":["https://openalex.org/P4310321814"],"host_organization_lineage_names":["AME Publishing Company"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Translational Cancer Research","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9922999739646912,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G145316093","display_name":"Bio-Physical Modeling of Immuno-Radiotherapy Combinations based on Patient Data","funder_award_id":"R21CA241918","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G7514298030","display_name":"A Computational Method to Calculate the Radiation Dose to CirculatingLymphocytes","funder_award_id":"R21CA248118","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G9000910585","display_name":"Integrating patient-specific clinical and biological factors towards individualizing utilization of proton and photon radiation therapy.","funder_award_id":"P01CA261669","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4362684563.pdf","grobid_xml":"https://content.openalex.org/works/W4362684563.grobid-xml"},"referenced_works_count":21,"referenced_works":["https://openalex.org/W2100519108","https://openalex.org/W2605630275","https://openalex.org/W2606367731","https://openalex.org/W2768434636","https://openalex.org/W2773643507","https://openalex.org/W2779503684","https://openalex.org/W2783760762","https://openalex.org/W2801510798","https://openalex.org/W2884395150","https://openalex.org/W2891915572","https://openalex.org/W2956407134","https://openalex.org/W2989013017","https://openalex.org/W3080889076","https://openalex.org/W3101948615","https://openalex.org/W3126376454","https://openalex.org/W3134151183","https://openalex.org/W3148827278","https://openalex.org/W3214365348","https://openalex.org/W4206362366","https://openalex.org/W4210772672","https://openalex.org/W4295350339"],"related_works":["https://openalex.org/W7121597476","https://openalex.org/W3090166752","https://openalex.org/W4404549321","https://openalex.org/W4401129816","https://openalex.org/W7165530268","https://openalex.org/W4295350339","https://openalex.org/W2972361096","https://openalex.org/W7152970177","https://openalex.org/W4312120480","https://openalex.org/W3137849805"],"abstract_inverted_index":{"We":[0],"congratulate":[1],"Juloori":[2],"et":[3],"al.":[4],"for":[5,123,253,301,380],"their":[6],"recently":[7],"published":[8],"phase":[9],"I":[10],"study":[11],"(1)":[12],"on":[13],"stereotactic":[14],"body":[15],"radiotherapy":[16,41],"(SBRT)":[17],"followed":[18],"by":[19,161,217,365],"nivolumab":[20,24,76,177,188,283,355],"plus":[21],"ipilimumab":[22],"or":[23,149],"alone":[25,77],"in":[26,48,74,80,98,173,186,205,257,262,272,281,294,320,342,350,353,370],"hepatocellular":[27],"carcinoma":[28],"(HCC).Their":[29],"results":[30,59,140,234],"are":[31],"an":[32,375],"excellent":[33],"example":[34],"of":[35,39,54,60,68,88,125,134,152,213,235,241,275,279,323,338,359,388],"both":[36],"the":[37,52,58,66,75,81,99,119,135,147,162,168,174,183,211,218,227,233,250,260,263,273,282,295,310,321,326,336,351,354,371,386],"promise":[38],"combining":[40],"(RT)":[42],"with":[43,103,277,287],"immune":[44],"checkpoint":[45],"inhibitors":[46],"(ICI)":[47],"HCC,":[49],"as":[50,164,357,391],"well":[51,159],"pitfalls":[53],"analyzing":[55],"and":[56,78,90,114,128,231,319,347,378,395],"interpreting":[57],"RT/ICI":[61,254],"combination":[62,155,255],"trials.The":[63],"authors":[64],"report":[65,84],"outcomes":[67],"thirteen":[69],"randomly":[70],"assigned":[71],"patients,":[72,138],"six":[73],"seven":[79],"nivolumab/ipilimumab":[82],"arm.They":[83],"a":[85,115,132,202,206,269],"higher":[86,91],"rate":[87,172,394],"toxicities":[89],"overall":[92,170,392],"response":[93,171,199,393],"rates":[94],"(4/7":[95],"vs.":[96],"0/6)":[97],"dual":[100],"ICI":[101],"arm,":[102,356],"two":[104,154,264,381],"patients":[105,193,280,344,352],"alive":[106],"after":[107],"at":[108],"least":[109],"3":[110],"years":[111],"without":[112],"progression":[113],"negative":[116],"PET":[117],"scan.As":[118],"trial":[120,190,237,246,265,303],"was":[121,180,308,313,329,348],"powered":[122],"evaluation":[124],"dose-limiting":[126],"toxicity":[127],"enrolled":[129],"less":[130],"than":[131,182],"quarter":[133],"planned":[136],"50":[137],"these":[139,153,343,383],"cannot":[141],"be":[142],"used":[143],"to":[144,224,291,316,331],"accurately":[145],"assess":[146],"absolute":[148],"relative":[150],"efficacy":[151],"regimens.This":[156],"point":[157],"is":[158,268,298,374],"made":[160],"authors,":[163],"they":[165],"mention":[166],"that":[167,335],"observed":[169,185],"SBRT":[175],"+":[176],"arm":[178,285],"(0%)":[179],"lower":[181,349],"15-20%":[184],"CheckMate-040":[187],"monotherapy":[189],"encompassing":[191],"262":[192],"(2).Particularly":[194],"when":[195],"evaluating":[196],"immunotherapy,":[197],"where":[198],"varies":[200],"widely,":[201],"few":[203],"outliers":[204],"small":[207,228],"population":[208],"can":[209,244],"invalidate":[210],"assumption":[212],"proportional":[214],"hazards":[215],"required":[216],"log-rank":[219],"test.However,":[220],"we":[221],"would":[222],"like":[223],"look":[225],"past":[226],"cohort":[229],"size":[230],"discuss":[232],"this":[236,245,302],"despite":[238],"its":[239],"lack":[240],"statistical":[242],"power.What":[243],"teach":[247],"us":[248],"about":[249],"way":[251],"forward":[252],"trials":[256],"HCC?When":[258],"comparing":[259],"populations":[261],"arms,":[266],"there":[267],"large":[270],"discrepancy":[271],"extent":[274],"disease,":[276,289],"50%":[278],"only":[284,292,305],"presenting":[286],"extra-hepatic":[288],"compared":[290],"14%":[293],"dual-ICI":[296],"arm.This":[297],"particularly":[299],"important":[300,376],"because":[304],"intrahepatic":[306],"disease":[307],"irradiated.Furthermore,":[309],"maximum":[311],"GTV":[312],"mostly":[314],"restricted":[315],"100":[317],"cc":[318],"case":[322],"multiple":[324],"lesions,":[325],"RT":[327],"target":[328,372],"left":[330],"investigator":[332],"discretion.This":[333],"means":[334],"fraction":[337],"tumor":[339],"burden":[340],"irradiated":[341],"varied":[345],"widely":[346],"half":[358],"them":[360],"had":[361],"extrahepatic":[362],"metastases,":[363],"which":[364],"design,":[366],"were":[367],"not":[368],"included":[369],"volume.This":[373],"distinction,":[377],"crucial":[379],"reasons.First,":[382],"limitations":[384],"restrict":[385],"usefulness":[387],"metrics":[389],"such":[390],"waterfall":[396],"plots.":[397]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":1}],"updated_date":"2026-10-30T12:39:25.321706","created_date":"2023-04-08T00:00:00"}
