DOI: 10.1002/mco2.493 ISSN: 2688-2663

A novel approach to evaluation of tumor response for advanced pulmonary adenocarcinoma using the intertumoral heterogeneity response score

Xinlong Zheng, Tao Lu, Shiwen Wu, Xiaoyan Lin, Jing Bai, Xiaohui Chen, Qian Miao, Jianqun Yan, Kan Jiang, Longfeng Zhang, Xiaobing Zheng, Haibo Wang, Yiquan Xu, Weijin Xiao, Cao Li, Wenying Peng, Jianming Ding, Qiaofeng Zhong, Zihua Zou, Shanshan Yang, Yujing Li, Sihui Chen, Qiuyu Zhang, Jianfeng Yan, Guofeng Tang, Yuandong Cai, Miao kang, Tony S. K. Mok, Gen Lin
  • Cell Biology
  • Biochemistry (medical)
  • Genetics (clinical)
  • Computer Science Applications
  • Drug Discovery
  • Genetics
  • Oncology
  • Immunology and Allergy


Treatment response and prognosis estimation in advanced pulmonary adenocarcinoma are challenged by the significant heterogeneity of the disease. The current Response Evaluation Criteria in Solid Tumors (RECIST) criteria, despite providing a basis for solid tumor response evaluation, do not fully encompass this heterogeneity. To better represent these nuances, we introduce the intertumoral heterogeneity response score (THRscore), a measure built upon and expanding the RECIST criteria. This retrospective study included patients with 3–10 measurable advanced lung adenocarcinoma lesions who underwent first‐line chemotherapy or targeted therapy. The THRscore, derived from the coefficient of variation in size for each measurable tumor before and 4–6 weeks posttreatment, unveiled a correlation with patient outcomes. Specifically, a high THRscore was associated with shorter progression‐free survival, lower tumor response rate, and a higher tumor mutation burden. These associations were further validated in an external cohort, confirming THRscore's effectiveness in stratifying patients based on progression risk and treatment response, and enhancing the utility of RECIST in capturing complex tumor behaviors in lung adenocarcinoma. These findings affirm the promise of THRscore as an enhanced tool for tumor response assessment in advanced lung adenocarcinoma, extending the RECIST criteria's utility.

More from our Archive