BACKGROUND Chemotherapy is an essential treatment for colorectal cancer(CRC)patients after surgery,but many patients do not benefit from chemotherapy because tumour heterogeneity results in varied responses.AIM To stu...BACKGROUND Chemotherapy is an essential treatment for colorectal cancer(CRC)patients after surgery,but many patients do not benefit from chemotherapy because tumour heterogeneity results in varied responses.AIM To study the effectiveness of in vitro chemosensitivity tests adenosine tripho-sphate-based tumour chemotherapy sensitivity test(ATP-TCA)for tailoring po-stoperative chemotherapy regimens for patients with CRC.METHODS Between January 2015 to December 2021,a total of 1549 CRC patients underwent surgery and in vitro chemosensitivity testing using ATP-TCA.A subset of 405 patients who met the survival assessment criteria were followed to collect data on overall survival(OS)and disease-free survival(DFS).Cox regression analysis revealed independent prognostic factors that affect OS and DFS for those re-ceiving oxaliplatin(L-OPH)and fluoropyrimidine-based regimens,aiding in the development of clinical predictive models.The relationships between the ATP-TCA results and clinical outcomes were analysed using the Kaplan-Meier method.RESULTS Tumour heterogeneity and resistance to multiple drugs were observed in 1549 patients.The sensitivity to 5-fluorouracil(5-FU)combined with L-OPH was tested among 1474 of these patients,yielding a sensitivity rate of 11.9%.ATP-TCA results were identified as an independent prognostic factor for DFS[P=0.002,hazard ratio(95%confidence interval):4.98(1.81-13.72)]in patients with resectable CRC.Compared with drug-resistant patients,sensitive CRC patients treated with 5-FU and L-OPH had significantly prolonged DFS(P=0.027).Further Kaplan-Meier analysis indicated that ATP-TCA sensitivity was significantly associated with improved OS(P=0.048)and DFS(P=0.003)in patients with stage III CRC.CONCLUSION The response of CRC patients to the combination regimen of 5-FU and L-OPH is heterogeneous.This study confirmed that the ATP-TCA is a valuable tool for predicting clinical outcomes,such as DFS,in patients with resectable CRC receiving chemotherapy.Although further validation with multicentre data is still necessary,these findings support that the ATP-TCA may function as a guiding tool for personalized chemotherapy administration,thereby optimizing treatment opportunities for patients.展开更多
基金Supported by the National Natural Science Foundation of China,No.U24A20765 and No.T2321005Jiangsu Provincial Science and Technology Plan Special Fund,No.BM2023003+5 种基金Jiangsu Provincial Medical Key Discipline,No.ZDXK202247the Priority Academic Program Development of the Jiangsu Higher Education InstitutesJiangsu Engineering Research Center on Drug Evaluation and Translation of Organoids/Organ Chip(2024)the Science and Technology Plan of Suzhou,No.SKYD2023183the Research Project Established by Chinese Pharmaceutical Association Hospital Pharmacy Department,No.CPA-Z05-ZC-2023002Gusu Health Talent Research Project,No.GSWS2022015.
文摘BACKGROUND Chemotherapy is an essential treatment for colorectal cancer(CRC)patients after surgery,but many patients do not benefit from chemotherapy because tumour heterogeneity results in varied responses.AIM To study the effectiveness of in vitro chemosensitivity tests adenosine tripho-sphate-based tumour chemotherapy sensitivity test(ATP-TCA)for tailoring po-stoperative chemotherapy regimens for patients with CRC.METHODS Between January 2015 to December 2021,a total of 1549 CRC patients underwent surgery and in vitro chemosensitivity testing using ATP-TCA.A subset of 405 patients who met the survival assessment criteria were followed to collect data on overall survival(OS)and disease-free survival(DFS).Cox regression analysis revealed independent prognostic factors that affect OS and DFS for those re-ceiving oxaliplatin(L-OPH)and fluoropyrimidine-based regimens,aiding in the development of clinical predictive models.The relationships between the ATP-TCA results and clinical outcomes were analysed using the Kaplan-Meier method.RESULTS Tumour heterogeneity and resistance to multiple drugs were observed in 1549 patients.The sensitivity to 5-fluorouracil(5-FU)combined with L-OPH was tested among 1474 of these patients,yielding a sensitivity rate of 11.9%.ATP-TCA results were identified as an independent prognostic factor for DFS[P=0.002,hazard ratio(95%confidence interval):4.98(1.81-13.72)]in patients with resectable CRC.Compared with drug-resistant patients,sensitive CRC patients treated with 5-FU and L-OPH had significantly prolonged DFS(P=0.027).Further Kaplan-Meier analysis indicated that ATP-TCA sensitivity was significantly associated with improved OS(P=0.048)and DFS(P=0.003)in patients with stage III CRC.CONCLUSION The response of CRC patients to the combination regimen of 5-FU and L-OPH is heterogeneous.This study confirmed that the ATP-TCA is a valuable tool for predicting clinical outcomes,such as DFS,in patients with resectable CRC receiving chemotherapy.Although further validation with multicentre data is still necessary,these findings support that the ATP-TCA may function as a guiding tool for personalized chemotherapy administration,thereby optimizing treatment opportunities for patients.
