{"id":"https://openalex.org/W7208815077","doi":"https://doi.org/10.64898/2026.09.01.748242","title":"Robust and Quality-of-Life-Aware Treatment Protocols in NSCLC using Deep Reinforcement Learning","display_name":"Robust and Quality-of-Life-Aware Treatment Protocols in NSCLC using Deep Reinforcement Learning","publication_year":2026,"publication_date":"2026-09-04","ids":{"openalex":"https://openalex.org/W7208815077","doi":"https://doi.org/10.64898/2026.09.01.748242"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.01.748242","doi":"https://doi.org/10.64898/2026.09.01.748242","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.01.748242","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/04/2026.09.01.748242.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/04/2026.09.01.748242.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5069863916","display_name":"Laura R. Jans\u00e9n-Storbacka","orcid":"https://orcid.org/0009-0006-1906-4575","observed_orcids":["https://orcid.org/0009-0006-1906-4575"]},"institutions":[{"id":"https://openalex.org/I98358874","display_name":"Delft University of Technology","ror":"https://ror.org/02e2c7k09","country_code":"NL","type":"education","lineage":["https://openalex.org/I98358874"]}],"countries":["NL"],"is_corresponding":true,"raw_author_name":"Laura R. Jans\u00e9n-Storbacka","raw_affiliation_strings":["Institute for Health Systems Science, Faculty of Technology, Policy and Management, Delft University of Technology, Delft, The Netherlands"],"raw_orcid":"https://orcid.org/0009-0006-1906-4575","affiliations":[{"raw_affiliation_string":"Institute for Health Systems Science, Faculty of Technology, Policy and Management, Delft University of Technology, Delft, The Netherlands","institution_ids":["https://openalex.org/I98358874"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5016567527","display_name":"Anne\u2010Marie C. Dingemans","orcid":"https://orcid.org/0000-0001-6105-182X","observed_orcids":["https://orcid.org/0000-0001-6105-182X","https://orcid.org/0000-0002-7069-6598"]},"institutions":[{"id":"https://openalex.org/I4210149908","display_name":"Erasmus MC Cancer Institute","ror":"https://ror.org/03r4m3349","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I2801952686","https://openalex.org/I4210149908"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Anne-Marie C. Dingemans","raw_affiliation_strings":["Department of Respiratory Medicine, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0001-6105-182X","affiliations":[{"raw_affiliation_string":"Department of Respiratory Medicine, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands","institution_ids":["https://openalex.org/I4210149908"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5037705191","display_name":"Kate\u0159ina Sta\u0148kov\u00e1","orcid":"https://orcid.org/0000-0002-4519-0325","observed_orcids":["https://orcid.org/0000-0002-4519-0325"]},"institutions":[{"id":"https://openalex.org/I98358874","display_name":"Delft University of Technology","ror":"https://ror.org/02e2c7k09","country_code":"NL","type":"education","lineage":["https://openalex.org/I98358874"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Kate\u0159ina Sta\u0148kov\u00e1","raw_affiliation_strings":["Institute for Health Systems Science, Faculty of Technology, Policy and Management, Delft University of Technology, Delft, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0002-4519-0325","affiliations":[{"raw_affiliation_string":"Institute for Health Systems Science, Faculty of Technology, Policy and Management, Delft University of Technology, Delft, The Netherlands","institution_ids":["https://openalex.org/I98358874"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5033992358","display_name":"Alethea Barbaro","orcid":"https://orcid.org/0000-0001-9856-2818","observed_orcids":["https://orcid.org/0000-0001-9856-2818"]},"institutions":[{"id":"https://openalex.org/I98358874","display_name":"Delft University of Technology","ror":"https://ror.org/02e2c7k09","country_code":"NL","type":"education","lineage":["https://openalex.org/I98358874"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Alethea B. T. Barbaro","raw_affiliation_strings":["Delft Institute of Applied Mathematics, Delft University of Technology, Delft, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0001-9856-2818","affiliations":[{"raw_affiliation_string":"Delft Institute of Applied Mathematics, Delft University of Technology, Delft, The Netherlands","institution_ids":["https://openalex.org/I98358874"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5082298867","display_name":"Sepinoud Azimi","orcid":"https://orcid.org/0000-0002-4739-9560","observed_orcids":["https://orcid.org/0000-0002-4739-9560"]},"institutions":[{"id":"https://openalex.org/I98358874","display_name":"Delft University of Technology","ror":"https://ror.org/02e2c7k09","country_code":"NL","type":"education","lineage":["https://openalex.org/I98358874"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Sepinoud Azimi","raw_affiliation_strings":["Institute for Health Systems Science, Faculty of Technology, Policy and Management, Delft University of Technology, Delft, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0002-4739-9560","affiliations":[{"raw_affiliation_string":"Institute for Health Systems Science, Faculty of Technology, Policy and Management, Delft University of Technology, Delft, The Netherlands","institution_ids":["https://openalex.org/I98358874"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5069863916"],"corresponding_institution_ids":["https://openalex.org/I98358874"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11829","display_name":"Mathematical Biology Tumor Growth","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/2611","display_name":"Modeling and Simulation"},"field":{"id":"https://openalex.org/fields/26","display_name":"Mathematics"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T11829","display_name":"Mathematical Biology Tumor Growth","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/2611","display_name":"Modeling and Simulation"},"field":{"id":"https://openalex.org/fields/26","display_name":"Mathematics"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10336","display_name":"Cancer Cells and Metastasis","score":9.999999747378752e-05,"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/T10482","display_name":"Mathematical and Theoretical Epidemiology and Ecology Models","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2604","display_name":"Applied Mathematics"},"field":{"id":"https://openalex.org/fields/26","display_name":"Mathematics"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/non-small-cell-lung-cancer","display_name":"non-small cell lung cancer","score":0.9819999933242798},{"id":"https://openalex.org/keywords/deep-reinforcement-learning","display_name":"deep reinforcement learning","score":0.8349999785423279},{"id":"https://openalex.org/keywords/adaptive-therapy","display_name":"adaptive therapy","score":0.9160000085830688},{"id":"https://openalex.org/keywords/treatment-resistance","display_name":"treatment resistance","score":0.8399999737739563},{"id":"https://openalex.org/keywords/erlotinib","display_name":"erlotinib","score":0.7730000019073486},{"id":"https://openalex.org/keywords/tumor-growth-modeling","display_name":"tumor growth modeling","score":0.7310000061988831},{"id":"https://openalex.org/keywords/two-population-model","display_name":"two-population model","score":0.7200000286102295},{"id":"https://openalex.org/keywords/quality-of-life","display_name":"quality of life","score":0.7559999823570251},{"id":"https://openalex.org/keywords/reward-shaping","display_name":"reward shaping","score":0.7379999756813049},{"id":"https://openalex.org/keywords/treatment-holidays","display_name":"treatment holidays","score":0.5619999766349792},{"id":"https://openalex.org/keywords/virtual-patients","display_name":"virtual patients","score":0.46299999952316284},{"id":"https://openalex.org/keywords/treatment-schedule-optimization","display_name":"treatment schedule optimization","score":0.42800000309944153},{"id":"https://openalex.org/keywords/time-to-progression","display_name":"time to progression","score":0.6610000133514404},{"id":"https://openalex.org/keywords/quality-adjusted-survival","display_name":"quality-adjusted survival","score":0.7820000052452087},{"id":"https://openalex.org/keywords/patient-preferences","display_name":"patient preferences","score":0.5120000243186951},{"id":"https://openalex.org/keywords/robustness","display_name":"robustness","score":0.4620000123977661}],"concepts":[{"id":"https://openalex.org/C63479239","wikidata":"https://www.wikidata.org/wiki/Q7353546","display_name":"Robustness (evolution)","level":3,"score":0.7210000157356262},{"id":"https://openalex.org/C97541855","wikidata":"https://www.wikidata.org/wiki/Q830687","display_name":"Reinforcement learning","level":2,"score":0.7032999992370605},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5591999888420105},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.46709999442100525},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.4636000096797943},{"id":"https://openalex.org/C2779951463","wikidata":"https://www.wikidata.org/wiki/Q7268788","display_name":"Quality of life (healthcare)","level":2,"score":0.42410001158714294},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.3481999933719635},{"id":"https://openalex.org/C3019816032","wikidata":"https://www.wikidata.org/wiki/Q2575340","display_name":"Cancer treatment","level":3,"score":0.33970001339912415},{"id":"https://openalex.org/C509974204","wikidata":"https://www.wikidata.org/wiki/Q180507","display_name":"Radiation therapy","level":2,"score":0.3271999955177307},{"id":"https://openalex.org/C72563966","wikidata":"https://www.wikidata.org/wiki/Q1303415","display_name":"Cohort","level":2,"score":0.32499998807907104},{"id":"https://openalex.org/C2983331546","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer therapy","level":3,"score":0.32359999418258667},{"id":"https://openalex.org/C4441509","wikidata":"https://www.wikidata.org/wiki/Q6418787","display_name":"Multimodal therapy","level":2,"score":0.30230000615119934},{"id":"https://openalex.org/C176217482","wikidata":"https://www.wikidata.org/wiki/Q860554","display_name":"Metric (unit)","level":2,"score":0.29100000858306885},{"id":"https://openalex.org/C2781067378","wikidata":"https://www.wikidata.org/wiki/Q17027399","display_name":"Interpretability","level":2,"score":0.289900004863739}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.01.748242","doi":"https://doi.org/10.64898/2026.09.01.748242","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.01.748242","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/04/2026.09.01.748242.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.09.01.748242","doi":"https://doi.org/10.64898/2026.09.01.748242","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.01.748242","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/04/2026.09.01.748242.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9391000270843506,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G7711722093","display_name":"Evolutionary games and population dynamics: from theory to applications","funder_award_id":"955708","funder_id":"https://openalex.org/F4320320300","funder_display_name":"European Commission"}],"funders":[{"id":"https://openalex.org/F4320320300","display_name":"European Commission","ror":"https://ror.org/00k4n6c32"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7208815077.pdf","grobid_xml":"https://content.openalex.org/works/W7208815077.grobid-xml"},"referenced_works_count":36,"referenced_works":["https://openalex.org/W1987012261","https://openalex.org/W2002903734","https://openalex.org/W2019607817","https://openalex.org/W2078075009","https://openalex.org/W2123558100","https://openalex.org/W2136417031","https://openalex.org/W2145980885","https://openalex.org/W2255756224","https://openalex.org/W2735758359","https://openalex.org/W2770572337","https://openalex.org/W2784371446","https://openalex.org/W2998744531","https://openalex.org/W3015131052","https://openalex.org/W3097007890","https://openalex.org/W3113932382","https://openalex.org/W3129959378","https://openalex.org/W3135217116","https://openalex.org/W3198461753","https://openalex.org/W4234576542","https://openalex.org/W4251104453","https://openalex.org/W4253594787","https://openalex.org/W4283643602","https://openalex.org/W4311631231","https://openalex.org/W4327860547","https://openalex.org/W4392929678","https://openalex.org/W4393935425","https://openalex.org/W4405386626","https://openalex.org/W4407925114","https://openalex.org/W4410779323","https://openalex.org/W4411160337","https://openalex.org/W4417046567","https://openalex.org/W7117116386","https://openalex.org/W7118290927","https://openalex.org/W7123427078","https://openalex.org/W7127910555","https://openalex.org/W7166125841"],"related_works":["https://openalex.org/W4391443196","https://openalex.org/W7123427078","https://openalex.org/W237719282","https://openalex.org/W4393852532","https://openalex.org/W2049655669","https://openalex.org/W2935343452","https://openalex.org/W7127910555","https://openalex.org/W4406332129","https://openalex.org/W4301337144","https://openalex.org/W7131785596"],"abstract_inverted_index":{"Abstract":[0],"Under":[1],"current":[2],"systemic":[3],"treatment":[4,29,36,46,76,122,134,154,195,260,290,342,355,396],"of":[5,35,62,118,130,223,336,377,387],"metastatic":[6],"cancer,":[7],"a":[8,108,141,146,169,231,329,334,359,410],"drug":[9],"is":[10,57,166,365],"frequently":[11],"prescribed":[12],"at":[13,358],"maximum":[14],"tolerable":[15],"dose":[16],"(MTD)":[17],"until":[18],"either":[19],"unacceptable":[20],"toxicity":[21],"or":[22,44,124],"progression.":[23,327],"Unfortunately,":[24],"in":[25,48,66,116,133,325,421],"many":[26],"patients":[27,157,180,338,351],"this":[28],"strategy":[30],"leads":[31],"to":[32,42,73,86,104,120,152,177,193,250,294,381,401],"the":[33,58,216,219,273,295,315,375,385],"development":[34],"resistance.":[37],"Evolutionary":[38],"therapy":[39,60,96,221],"approaches":[40,97],"aim":[41],"forestall":[43],"delay":[45],"resistance":[47,383],"cancer":[49,162],"by":[50,145],"exploiting":[51],"eco-evolutionary":[52],"interactions.":[53],"A":[54],"well-known":[55],"implementation":[56],"adaptive":[59,220],"protocol":[61,222,319],"Zhang":[63,224,316],"et":[64,225,317],"al.,":[65,226],"which":[67],"tumour":[68,149,361,389],"burden":[69,362],"thresholds":[70],"are":[71],"used":[72,85],"guide":[74],"strategic":[75],"holidays.":[77],"Deep":[78],"reinforcement":[79],"learning":[80],"(DRL)":[81],"has":[82,98,112],"recently":[83],"been":[84],"optimise":[87],"these":[88,407],"approaches.":[89],"However,":[90],"research":[91],"combining":[92],"DRL":[93,142,217,279,305,372],"with":[94,158,181,184],"evolutionary":[95,419],"so":[99],"far":[100],"focused":[101],"on":[102,168,190,198,333],"time":[103,274],"progression":[105],"(TTP)":[106],"as":[107,272,425],"performance":[109],"metric,":[110],"and":[111,197,202,213,227,236,286,322,352,417],"not":[113],"quantified":[114],"safety":[115],"terms":[117],"robustness":[119,192,212,232],"delayed":[121,194],"restart":[123,196],"included":[125],"patient":[126,171,242,404],"preferences":[127,201,254],"regarding":[128],"quality":[129],"life":[131],"(QoL)":[132],"design.":[135,261],"In":[136,313],"our":[137,264],"study,":[138],"we":[139,188,246,266],"use":[140],"agent":[143,165],"informed":[144,412],"mathematical":[147],"two-population":[148],"growth":[150],"model":[151],"design":[153],"schedules":[155],"for":[156,347,414],"non-small":[159],"cell":[160],"lung":[161],"(NSCLC).":[163],"The":[164,278],"trained":[167,332],"virtual":[170,337],"cohort":[172,335],"using":[173],"parameters":[174],"previously":[175,349],"fitted":[176],"data":[178],"from":[179],"NSCLC":[182],"treated":[183],"erlotinib.":[185],"Beyond":[186],"TTP,":[187,211,284],"focus":[189],"improving":[191],"how":[199,252,395],"individual":[200],"values":[203],"impact":[204],"QoL":[205,214,253],"experienced":[206],"during":[207],"treatment.":[208],"We":[209,229],"compare":[210,237],"under":[215,304,311],"policy,":[218],"MTD.":[228,312],"introduce":[230],"metric":[233],"\u201cmargin-to-failure\u201d":[234],"(MTF),":[235],"quality-adjusted-survival":[238],"(QAS)":[239],"across":[240,288],"different":[241,268,403],"preference":[243],"profiles.":[244],"Finally,":[245],"explore":[247],"reward":[248],"shaping":[249,392],"assess":[251],"can":[255,373],"be":[256,399],"incorporated":[257],"into":[258],"DRL-based":[259],"To":[262],"evaluate":[263],"results,":[265],"consider":[267],"decision":[269,291,300],"intervals,":[270],"defined":[271],"between":[275],"dosing":[276],"adjustments.":[277],"policy":[280,331],"achieved":[281,310],"greater":[282],"median":[283],"MTF,":[285],"QAS":[287],"all":[289],"intervals":[292,301],"compared":[293],"other":[296],"two":[297],"protocols.":[298],"As":[299],"increased,":[302],"TTP":[303,346],"declined":[306],"gradually":[307],"towards":[308],"that":[309,344,354,371],"contrast,":[314],"al.":[318],"performed":[320],"inconsistently":[321],"could":[323,398],"result":[324],"premature":[326],"Additionally,":[328],"population-level":[330],"produced":[339],"an":[340],"interpretable":[341],"rule":[343],"extended":[345],"most":[348],"unseen":[350],"indicated":[353],"should":[356],"resume":[357],"lower":[360],"when":[363],"monitoring":[364],"less":[366],"frequent.":[367],"These":[368],"findings":[369],"show":[370],"balance":[374],"benefit":[376],"preserving":[378],"drug-sensitive":[379],"cells":[380],"suppress":[382],"against":[384],"risk":[386],"unsafe":[388],"regrowth.":[390],"Reward":[391],"further":[393],"showed":[394],"strategies":[397],"adjusted":[400],"reflect":[402],"preferences.":[405],"Together,":[406],"results":[408],"provide":[409],"biologically":[411],"approach":[413],"designing":[415],"robust":[416],"patient-centred":[418],"therapies":[420],"fast-growing":[422],"cancers":[423],"such":[424],"NSCLC.":[426]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2026-09-06T00:00:00"}
