Wei Wang1, Yu Zhang2, Ying Peng1, Kai-Zhou Jin3, Yuan-Liang Li4, Yao Liang1, Huang-Ying Tan4, Xian-Jun Yu3, Zhi-Wei Zhou1, Jie Chen5. 1. Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. 2. Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 3. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. 4. Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China. 5. Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, chen0jie@hotmail.com.
Abstract
OBJECTIVE: The efficacy of the capecitabine/temozolomide (CAPTEM) regimen has been demonstrated in metastatic neuroendocrine neoplasms (NENs), but because of varying response rates among the patients, biomarkers to predict its response are greatly needed. Here, we investigated the clinical utility of a Ki-67 index to predict the CAPTEM regimen objective responses and select patients who could benefit from this regimen. METHODS: Metastatic NENs patients treated with the CAPTEM regimen from 4 high-volume medical centers were selected and grouped in a training and validation cohort. The classification and regression tree (CART) was generated to identify the optimal threshold of Ki-67 for stratifying the patients into different Ki-67 range groups based on their response to the CAPTEM regimen. RESULTS AND CONCLUSIONS: The overall response rate (ORR) and disease control rate of the entire cohort (N = 151) were 26.5 and 76.2%, respectively, with a median progression-free survival (PFS) of 12.0 months. CART analysis showed that patients in the Ki-67 range group 10-40% demonstrated a significantly higher ORR than those in Ki-67 >40 and <10% groups (p < 0.001 in the training cohort and p = 0.036 in the validation cohort). Response to the CAPTEM regimen was not influenced by the expression of O6-methylguanine-DNA methyltransferase or primary tumor location. Multivariate analysis identified the Ki-67 index as the only independent prognostic factor for overall survival (p = 0.031) and PFS (p = 0.006). The proposed Ki-67 index was externally validated and could be used to clinically identify suitable metastatic NENs patients who could achieve an optimal cytoreduction using the CAPTEM regimen.
OBJECTIVE: The efficacy of the capecitabine/temozolomide (CAPTEM) regimen has been demonstrated in metastatic neuroendocrine neoplasms (NENs), but because of varying response rates among the patients, biomarkers to predict its response are greatly needed. Here, we investigated the clinical utility of a Ki-67 index to predict the CAPTEM regimen objective responses and select patients who could benefit from this regimen. METHODS: Metastatic NENs patients treated with the CAPTEM regimen from 4 high-volume medical centers were selected and grouped in a training and validation cohort. The classification and regression tree (CART) was generated to identify the optimal threshold of Ki-67 for stratifying the patients into different Ki-67 range groups based on their response to the CAPTEM regimen. RESULTS AND CONCLUSIONS: The overall response rate (ORR) and disease control rate of the entire cohort (N = 151) were 26.5 and 76.2%, respectively, with a median progression-free survival (PFS) of 12.0 months. CART analysis showed that patients in the Ki-67 range group 10-40% demonstrated a significantly higher ORR than those in Ki-67 >40 and <10% groups (p < 0.001 in the training cohort and p = 0.036 in the validation cohort). Response to the CAPTEM regimen was not influenced by the expression of O6-methylguanine-DNA methyltransferase or primary tumor location. Multivariate analysis identified the Ki-67 index as the only independent prognostic factor for overall survival (p = 0.031) and PFS (p = 0.006). The proposed Ki-67 index was externally validated and could be used to clinically identify suitable metastatic NENs patients who could achieve an optimal cytoreduction using the CAPTEM regimen.
Authors: R Dumke; C Dumke; F Eberle; Ch Nimsky; U Keber; R Engenhart-Cabillic; S Lautenschläger Journal: Strahlenther Onkol Date: 2022-05-25 Impact factor: 4.033
Authors: David L Chan; Emily K Bergsland; Jennifer A Chan; Rujuta Gadgil; Thorvardur R Halfdanarson; Kathleen Hornbacker; Virginia Kelly; Pamela L Kunz; Patrick W McGarrah; Nitya P Raj; Diane L Reidy; Alia Thawer; Julia Whitman; Linda Wu; Christoph Becker; Simron Singh Journal: Oncologist Date: 2021-08-21