medwireNews: The definition and incidence of hyperprogressive disease (HPD) vary widely across studies of people undergoing immune checkpoint inhibitor (ICI) therapy for cancer, results of a systematic review and meta-analysis show.
Kyung Won Kim (University of Ulsan College of Medicine, Seoul, Korea) and colleagues say their findings “indicate the need for establishing uniform and clinically relevant criteria based on currently available evidence.”
Kim and team reviewed data from 24 clinical trials and observational studies that included a total of 3109 patients treated with ICIs. Nine of the studies included various tumor types (≥3 tumor types in each study), eight solely included patients with non-small-cell lung cancer, and the remaining seven included patients with other single tumor types.
The researchers report in JAMA Network Open that the definitions of HPD, which is a recognized pattern of rapid tumor progression during ICI treatment, could be divided into four main categories according to the calculation of tumor growth acceleration.
- Tumor growth rate (TGR) ratio, which compares the speed of increase in tumor volume before and after treatment.
- Tumor growth kinetics (TGK) ratio, which compares the speed of increase in tumor size before and after treatment.
- Early tumor burden increase between baseline and first post-treatment imaging.
- Combinations of the above categories.
The majority (83.3%) of studies required a calculation of tumor growth acceleration (TGR and/or TGK ratio) to define HPD. Only four studies included new lesions as well as target lesions when measuring HPD.
Kim et al found that the incidence of HPD varied widely across the studies, from 5.9% to 43.1%, with a pooled rate of 13.4% overall.
Pooled incidence also varied according to the definition of HPD. The highest rate, of 20.6%, occurred when early tumor burden increase criteria were used, followed by 15.8% with the TGK ratio, 12.4% when using combined criteria, and 9.4% when the definition of HPD was based on the TGR ratio.
In an accompanying commentary, Kartik Sehgal, from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA, describes how the study highlights “various challenges in accurately detecting hyperprogressive disease with these nonuniform criteria.”
He says that these challenges include “the lack of consideration of development of new lesions or changes in nontarget lesions; lack of consensus regarding optimal time for imaging assessment; discrepancy with the commonly used Response Evaluation Criteria in Solid Tumors; and reliance on prebaseline imaging for measurement of tumor growth acceleration, which is often not available (especially in the treatment naïve settings).”
Sehgal concludes: “The major barrier to development of a robust evidence-based knowledge base [according to] risk factors, pathophysiology, early detection, and management of hyperprogressive disease remains the lack of concise and simple-to-use assessment criteria that can be used without the requirements of prebaseline imaging studies and complicated calculations.”
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JAMA Netw Open 2021; 4: e211136
JAMA Netw Open 2021; 4: e211839