The Effect of Intrathoracic Lesion Location on Initial Tyrosine Kinase Inhibitor Response in Advanced Oncogene-Addicted Non-Small Cell Lung Cancer: A Comparison Between RECIST 1.1 and a Novel Method of Response Assessment (MAX)

Clin Lung Cancer. 2022 Dec;23(8):e501-e509. doi: 10.1016/j.cllc.2022.08.004. Epub 2022 Aug 7.


Introduction: Different subtypes of non-small cell lung cancer (NSCLC) are associated with different patterns of metastatic spread. Anatomic location of lesions in the chest may influence patterns of cancer growth and the shrinkage to therapy. Consequently, lesion location could affect apparent response rates per RECIST. We sought to explore this and develop, as needed, treatment response assessments less affected by the location.

Methods: Cases of advanced oncogene-addicted NSCLC (EGFR, ALK, and ROS1) with pre- and on-therapy imaging during initial targeted therapy were identified. Lesions located in the lung parenchyma, pleural space or intra-thoracic lymph nodes were identified and analyzed separately from each other by RECIST 1.1 (unidimensional measurements) and by a novel MAX methodology (bidimensional measurements) which takes the axis with the greatest absolute percentage change on therapy in each location as the representative measurement.

Results: Three hundred three patients with 446 unidimensional measured lesions were included for RECIST analysis. Two hundred forty nine patients with 386 bidimensional measured lesions were included for MAX analysis, as well as the analysis comparing RECIST and MAX. Intrathoracic location significantly impacted percentage shrinkage and the response rate per RECIST. The response rates for pleural, intra-parenchymal and nodal lesions were 34.1%, 49.6%, and 68.3%, respectively (P = .0002). The MAX methodology both increased the apparent treatment effect and made it consistent between intrathoracic locations. For pleural, parenchymal and nodal lesions, the MAX calculated response rate were 83.7%, 72.2%, and 75.4%, respectively (P-value = .24).

Conclusion: Intrathoracic lesion location affects RECIST-based treatment effectiveness estimations. The MAX methodology neutralizes location effect when examining impact of treatment and should be explored further.

Keywords: Lymph node; Parenchymal lung; Pleura; Targeted therapy.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Humans
  • Lung Neoplasms* / pathology
  • Oncogenes
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Response Evaluation Criteria in Solid Tumors
  • Tomography, X-Ray Computed / methods


  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins