The value of PFS36 as a primary endpoint for radiotherapy trials in patients with LACC: individual patient data from the Chinese NCC and validation from 26 RCTs
Objective: A conventional endpoint for locally advanced cervical cancer (LACC) clinical trials is overall survival (OS) with five years of follow-up. The primary hypothesis was that progression-free survival (PFS) with three years of follow-up (PFS36) would be an appropriate primary surrogate endpoi...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-04-01
|
| Series: | Journal of the National Cancer Center |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667005424001236 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850202186966892544 |
|---|---|
| author | Xi Yang Yuanyuan Zhang Shuangzheng Jia Yong Yang Jie Zhu Wei Li Lingying Wu Jusheng An Manni Huang |
| author_facet | Xi Yang Yuanyuan Zhang Shuangzheng Jia Yong Yang Jie Zhu Wei Li Lingying Wu Jusheng An Manni Huang |
| author_sort | Xi Yang |
| collection | DOAJ |
| description | Objective: A conventional endpoint for locally advanced cervical cancer (LACC) clinical trials is overall survival (OS) with five years of follow-up. The primary hypothesis was that progression-free survival (PFS) with three years of follow-up (PFS36) would be an appropriate primary surrogate endpoint. Materials and methods: The primary hypothesis, which was developed from our data, was further investigated using phase III randomized controlled trials and then externally validated using retrospective studies up to 2023. Correlation analysis at the treatment-arm level was performed between 2-, 3-, 4-, and 5-year PFS rates and 5-year OS. Results: A total of 613 patients with histologically confirmed cervical cancer who underwent radiotherapy or chemoradiation at our institute between January 2010 and December 2013 were eligible. The recurrence rates for years 1 through 5 were 12.9%, 7.3%, 3%, 2.3%, and 1.8%, respectively. Patients who did not achieve PFS36 had a 5-year OS rate of 30.3%. However, patients who achieved PFS36 had a 5-year OS rate of 98.2%. Further data were extracted from 26 randomized phase III trials on LACC. The trials included 55 arms, with a pooled sample size of 7,281 patients. Trial-level surrogacy results revealed that PFS36 (r2, 0.732) was associated with 5-year OS. The correlation between PFS36 and OS was externally validated using independent retrospective data. Conclusion: A significant positive correlation was found between PFS36 and OS at 5 years of follow-up both within patients and across trials. These results suggest that PFS36 is an appropriate endpoint for LACC clinical trials of radiotherapy-based regimens. |
| format | Article |
| id | doaj-art-aba2632091c748528f4099cfd52829f0 |
| institution | OA Journals |
| issn | 2667-0054 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of the National Cancer Center |
| spelling | doaj-art-aba2632091c748528f4099cfd52829f02025-08-20T02:11:50ZengElsevierJournal of the National Cancer Center2667-00542025-04-015219320210.1016/j.jncc.2024.08.003The value of PFS36 as a primary endpoint for radiotherapy trials in patients with LACC: individual patient data from the Chinese NCC and validation from 26 RCTsXi Yang0Yuanyuan Zhang1Shuangzheng Jia2Yong Yang3Jie Zhu4Wei Li5Lingying Wu6Jusheng An7Manni Huang8Department of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Radiation Oncology, Fujian Medical University Union Hospital, Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors (Fujian Medical University), Fuzhou, ChinaDepartment of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Corresponding authors.Department of Gynecological Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Corresponding authors.Objective: A conventional endpoint for locally advanced cervical cancer (LACC) clinical trials is overall survival (OS) with five years of follow-up. The primary hypothesis was that progression-free survival (PFS) with three years of follow-up (PFS36) would be an appropriate primary surrogate endpoint. Materials and methods: The primary hypothesis, which was developed from our data, was further investigated using phase III randomized controlled trials and then externally validated using retrospective studies up to 2023. Correlation analysis at the treatment-arm level was performed between 2-, 3-, 4-, and 5-year PFS rates and 5-year OS. Results: A total of 613 patients with histologically confirmed cervical cancer who underwent radiotherapy or chemoradiation at our institute between January 2010 and December 2013 were eligible. The recurrence rates for years 1 through 5 were 12.9%, 7.3%, 3%, 2.3%, and 1.8%, respectively. Patients who did not achieve PFS36 had a 5-year OS rate of 30.3%. However, patients who achieved PFS36 had a 5-year OS rate of 98.2%. Further data were extracted from 26 randomized phase III trials on LACC. The trials included 55 arms, with a pooled sample size of 7,281 patients. Trial-level surrogacy results revealed that PFS36 (r2, 0.732) was associated with 5-year OS. The correlation between PFS36 and OS was externally validated using independent retrospective data. Conclusion: A significant positive correlation was found between PFS36 and OS at 5 years of follow-up both within patients and across trials. These results suggest that PFS36 is an appropriate endpoint for LACC clinical trials of radiotherapy-based regimens.http://www.sciencedirect.com/science/article/pii/S2667005424001236Locally advanced cervical cancerRadiotherapySurrogate endpointProgression-free survivalOverall survival |
| spellingShingle | Xi Yang Yuanyuan Zhang Shuangzheng Jia Yong Yang Jie Zhu Wei Li Lingying Wu Jusheng An Manni Huang The value of PFS36 as a primary endpoint for radiotherapy trials in patients with LACC: individual patient data from the Chinese NCC and validation from 26 RCTs Journal of the National Cancer Center Locally advanced cervical cancer Radiotherapy Surrogate endpoint Progression-free survival Overall survival |
| title | The value of PFS36 as a primary endpoint for radiotherapy trials in patients with LACC: individual patient data from the Chinese NCC and validation from 26 RCTs |
| title_full | The value of PFS36 as a primary endpoint for radiotherapy trials in patients with LACC: individual patient data from the Chinese NCC and validation from 26 RCTs |
| title_fullStr | The value of PFS36 as a primary endpoint for radiotherapy trials in patients with LACC: individual patient data from the Chinese NCC and validation from 26 RCTs |
| title_full_unstemmed | The value of PFS36 as a primary endpoint for radiotherapy trials in patients with LACC: individual patient data from the Chinese NCC and validation from 26 RCTs |
| title_short | The value of PFS36 as a primary endpoint for radiotherapy trials in patients with LACC: individual patient data from the Chinese NCC and validation from 26 RCTs |
| title_sort | value of pfs36 as a primary endpoint for radiotherapy trials in patients with lacc individual patient data from the chinese ncc and validation from 26 rcts |
| topic | Locally advanced cervical cancer Radiotherapy Surrogate endpoint Progression-free survival Overall survival |
| url | http://www.sciencedirect.com/science/article/pii/S2667005424001236 |
| work_keys_str_mv | AT xiyang thevalueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT yuanyuanzhang thevalueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT shuangzhengjia thevalueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT yongyang thevalueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT jiezhu thevalueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT weili thevalueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT lingyingwu thevalueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT jushengan thevalueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT mannihuang thevalueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT xiyang valueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT yuanyuanzhang valueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT shuangzhengjia valueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT yongyang valueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT jiezhu valueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT weili valueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT lingyingwu valueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT jushengan valueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts AT mannihuang valueofpfs36asaprimaryendpointforradiotherapytrialsinpatientswithlaccindividualpatientdatafromthechinesenccandvalidationfrom26rcts |