Comprehensive Clinical and Genetic Characterization of Hyperprogression Based on Volumetry in Advanced Non–Small Cell Lung Cancer Treated With Immune.

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Comprehensive Clinical and Genetic Characterization of Hyperprogression Based on Volumetry in Advanced Non–Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitor Youjin Kim, MD, Chu Hyun Kim, MD, Ho Yun Lee, MD, PhD, Se-Hoon Lee, MD, PhD, Hong Sook Kim, PhD, Sook Lee, MS, Hongui Cha, MS, Sungjun Hong, MS, Kyunga Kim, PhD, Sang Won Seo, MD, PhD, Jong-Mu Sun, MD, PhD, Myung-Ju Ahn, MD, PhD, Jin Seok Ahn, MD, PhD, Keunchil Park, MD, PhD Journal of Thoracic Oncology Volume 14, Issue 9, Pages 1608-1618 (September 2019) DOI: 10.1016/j.jtho.2019.05.033 Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Comparison of overall survival (OS) between patients with hyperprogressive disease (HPD) and patients without HPD. (A) OS according to response by volumetric measurement. (B) OS according to response by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). (C) Hazard rate plot constructed by using Kaplan-Meier analysis for patients with HPD and patients without HPD. CI, confidence interval; HPDV, patients with HPD assessed by volumetry; non-HPDV, patients without HPD assessed by volumetry; HPDR, patients with HPD assessed by RECIST 1.1; non-HPDR, patients without HPD assessed by RECIST 1.1. Journal of Thoracic Oncology 2019 14, 1608-1618DOI: (10.1016/j.jtho.2019.05.033) Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Discrepancy between volumetric measurement of hyperprogressive disease (HPD) according to the Response Evaluation Criteria in Solid Tumors RECIST, version 1.1 (RECIST 1.1). (A) Progression pattern in patients with discrepancy between the two assessment methods. (Left) Patients with HPD assessed by volumetry (HPDV) and patients without HPD assessed by RECIST 1.1 (non-HPDR) (n = 13); (right) patients without HPD assessed by volumetry (non-HPDV) and patients with HPD assessed by RECIST 1.1 (HPDR) (n = 9). (B) Comparison of overall survival between patients with HPD and patients without HPD among patients without HPD when categorized by RECIST 1.1. OS, overall survival; CI, confidence interval. Journal of Thoracic Oncology 2019 14, 1608-1618DOI: (10.1016/j.jtho.2019.05.033) Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Genomic alterations associated with hyperprogressive disease (HPD), no HPD (non-HPD), stable disease, and partial response (PR) in anti–programmed death 1/programmed death ligand 1 (PD-L1)–treated patients (16 in patients with HPD assessed by volumetry, 28 in patients without HPD assessed by volumetry, 39 in patients with stable disease, and 27 in patients with a PR). Genes with significantly different mutation patterns between patients with HPD and patients without HPD are presented. Patient characteristics and clinical history are summarized in the top panel. ICI, immune checkpoint inhibitor; TMB, tumor mutation burden; RAF1, Raf-1 proto-oncogene, serine/threonine kinase gene; CDKN2A, cyclin dependent kinase inhibitor 2A gene; STK11, serine/threonine kinase 11 gene; JAK2, Janus kinase 2 gene; MDM2, MDM2 proto-oncogene gene; B2M, beta-2-microglobulin gene; NFE2L2, nuclear factor erythroid 2, like 2 gene; JAK1, Janus kinase 1 gene; BACH1, BTB domain and CNC homolog 1 gene; MDM4, MDM4 regulator of p53 gene; AMP, amplification; DEL, deletion; SNV, single-nucleotide variant; ADC, adenocarcinoma; SQCC, squamous cell carcinoma. Journal of Thoracic Oncology 2019 14, 1608-1618DOI: (10.1016/j.jtho.2019.05.033) Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Case of hyperprogressive disease (HPD). (A and B) Before baseline. (C and D) At baseline. (E and F) At first imaging. According to the Response Evaluation Criteria in Solid Tumors RECIST, version 1.1, criteria, the primary lung lesion in the right lower lobe is considered a target lesion (thick arrow). Small, ill-defined lung-to-lung metastases and multiple scattered hepatic and lymph node metastases can be observed. Lesions that harbor significantly different mutation patterns are marked by arrowheads. Appearance of new lesions (black arrows) suggests progression of the disease (not evaluated quantitatively). Journal of Thoracic Oncology 2019 14, 1608-1618DOI: (10.1016/j.jtho.2019.05.033) Copyright © 2019 International Association for the Study of Lung Cancer Terms and Conditions