Hyperprogressive Disease in Patients with Non-Small Cell Lung Cancer Treated with Checkpoint Inhibitors: The Role of 18F-FDG PET/CT

Angelo Castello, Sabrina Rossi, Emanuela Mazziotti, Luca Toschi, Egesta Lopci

Research output: Contribution to journalArticlepeer-review


A new pattern of response, so-called hyperprogressive disease (HPD), is emerging during treatment with immune checkpoint inhibitors (ICIs). Our aim was to investigate the prevalence of such a phenomenon and to assess its association with clinical variables and metabolic parameters by 18F-FDG PET/CT. Methods: Data from 50 patients (34 men and 16 women; median age, 73 y) with non-small cell lung carcinoma treated with ICIs were prospectively collected. All patients underwent contrast-enhanced CT, 18F-FDG PET/CT, and complete peripheral blood sampling at baseline before ICI treatment. HPD was defined according to clinical and radiologic criteria. Because of rapid disease progression or worsening of clinical condition, radiologic response assessment was available for only 46 of the 50 patients. Overall survival (OS) was analyzed using the Kaplan-Meier method and the log-rank test. A Cox proportional hazards regression analysis was used to evaluate factors independently associated with OS. Median follow-up was 12.4 mo (range, 9.7-15.2 mo). Results: We identified the following response categories: 10 cases as complete or partial response, 17 cases as stable disease, 5 cases as progressive disease, and 14 cases as HPD. Among metabolic parameters, we observed a statistically significant association between HPD status and tumor burden, expressed by both TLG (756.1 cm3 for HPD vs. 475.6 cm3 for non-HPD, P = 0.042) and MTV (287.3 for HPD vs. 62.1 for non-HPD, P = 0.011). Among clinical variables, 12 of 14 patients (85.7%) within the HPD group, compared with 8 of 32 patients (25%) in the non-HPD group, had more than 2 metastatic sites (P < 0.001). In addition, the derived neutrophil-to-lymphocyte ratio and platelet count were significantly associated with HPD status (P = 0.038 and P = 0.025, respectively). Survival analysis showed a median OS of 4 mo for the HPD group, compared with 15 mo for the non-HPD group (P = 0.003). Likewise, median OS was significantly different when we considered all the response categories: complete or partial response, stable disease, progressive disease, and HPD (P = 0.001). Finally, multivariate analysis identified metabolic tumor volume and derived neutrophil-to-lymphocyte ratio as independent predictors for OS. Conclusion: Our results suggest that the use of ICIs might represent a concern in patients with high metabolic tumor burden and inflammatory indices at baseline. However, additional studies are needed.

Original languageEnglish
Pages (from-to)821-826
Number of pages6
JournalJournal of Nuclear Medicine
Issue number6
Publication statusPublished - Jun 2020


  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen/antagonists & inhibitors
  • Carcinoma, Non-Small-Cell Lung/diagnostic imaging
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Lung Neoplasms/diagnostic imaging
  • Male
  • Positron Emission Tomography Computed Tomography/methods
  • Programmed Cell Death 1 Receptor/antagonists & inhibitors
  • Proportional Hazards Models


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