A simulated trial with reinforcement learning for the efficacy of Irinotecan and Ifosfamide versus Topotecan in relapsed, extensive stage small cell lung cancer.
Humans
Topotecan
/ administration & dosage
Small Cell Lung Carcinoma
/ drug therapy
Irinotecan
/ therapeutic use
Lung Neoplasms
/ drug therapy
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Ifosfamide
/ administration & dosage
Neoplasm Recurrence, Local
/ drug therapy
Male
Female
Proportional Hazards Models
Neoplasm Staging
Middle Aged
Computer Simulation
Treatment Outcome
Aged
Chemotherapy
Machine learning
Reinforcement learning
Relapsed disease
Simulated clinical trial
Small cell lung cancer
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
30 Sep 2024
30 Sep 2024
Historique:
received:
08
05
2024
accepted:
24
09
2024
medline:
1
10
2024
pubmed:
1
10
2024
entrez:
30
9
2024
Statut:
epublish
Résumé
Synthetic data may proxy clinical data. At the absence of direct clinical data, this study aimed to compare Irinotecan and Ifosfamide (II) with Topotecan in synthetic, recurrent small cell lung cancer (SCLC) patients within a simulated clinical trial. Two simulation stages were conducted. Initially, 200 recurrent SCLC cases were simulated to replicate a previous phase 3 trial, testing the utility of Cox proportional hazards model and simulation methodology together, where patients were randomized to receive Cyclophosphamide, Adriamycin, Vincristine (CAV) or Topotecan. In the second stage, 600 recurrent SCLC patients were simulated and randomized to compare Topotecan versus II in terms of overall survival (OAS), using Reinforcement Learning (RL) and Cox proportional hazards model. CAV versus Topotecan comparison showed no statistical difference in overall survival (hazard ratio (HR): 0.89, 95% CI: 0.67-1.18, P = 0.418), aligning with the original clinical trial. For the Topotecan versus II comparison, the RL framework significantly favored the II arm (mean reward points: 193.43 versus - 251.82, permutation P < 0.0001). Likewise, II arm exhibited superior median OAS compared to Topotecan arm (11.12 versus 6.30 months). HR was 0.44 (95% CI: 0.38-0.52) with P < 0.0001, in favor of II. Artificial trial results for CAV versus Topotecan matched the original trial, confirming indifference of OAS. Additionally, II yielded superior overall survival compared to Topotecan in recurrent SCLC patients. These demonstrate the potential of RL and simulation in conjunction with Cox modelling for similar studies. However, definitive conclusions necessitate a randomized clinical trial between II and Topotecan in this patient cohort.
Identifiants
pubmed: 39350046
doi: 10.1186/s12885-024-12985-1
pii: 10.1186/s12885-024-12985-1
doi:
Substances chimiques
Topotecan
7M7YKX2N15
Irinotecan
7673326042
Ifosfamide
UM20QQM95Y
Types de publication
Journal Article
Comparative Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1207Informations de copyright
© 2024. The Author(s).
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