Comparison of radiological criteria for hyperprogressive disease in response to immunotherapy

Morais, Ana; Miguel, Maria J. de; Rebollo, José Miguel Cárdenas; Calvo, Emiliano

doi:10.1016/j.ctrv.2020.102116

Cited by 13 publications

(13 citation statements)

References 18 publications

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“…In our datasets of patients, PsP ( Figure 1A ) was defined as immune unconfirmed progressive disease (iUPD) during evaluation and further response classified as immune complete response (iCR), immune partial response (iPR), or immune stable disease (iSD) ( 22 ). HPD ( Figure 1B ) criteria, which are as follows in accordance with previous studies: 1) progression at first post-ICI, 2) increase in tumor size over 50%, and 3) over two-fold increase in progression rate ( 23 , 24 ). We also defined other immune confirmed progressive diseases (iCPDs) except for HPD as sPD by iRECIST criteria.…”

Section: Methodssupporting

confidence: 89%

CT-Based Peritumoral and Intratumoral Radiomics as Pretreatment Predictors of Atypical Responses to Immune Checkpoint Inhibitor Across Tumor Types: A Preliminary Multicenter Study

Feng

Lin

et al. 2021

Front. Oncol.

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ObjectiveTo develop and validate a new strategy based on radiomics features extracted from intra- and peritumoral regions on CT images for the prediction of atypical responses to the immune checkpoint inhibitor (ICI) in cancer patients.MethodsIn total, 135 patients derived from five hospitals with pathologically confirmed malignancies receiving ICI were included in this retrospective study. Atypical responses including pseudoprogression (PsP) and hyperprogression disease (HPD) were identified as their definitions. A subgroup of standard progression disease (sPD) in 2018 was also involved in this study. Based on pretreatment CT imaging, a total of 107 features were extracted from intra- and peri-tumoral regions, respectively. The least absolute shrinkage and selection operator (Lasso) algorithm was used for feature selection, and multivariate logistic analysis was used to develop radiomics signature (RS). Finally, a total of nine RSs, derived from intra-tumoral, peri-tumoral, and combination of both regions, were built respectively to distinguish PsP vs. HPD, PsP vs. sPD, and HPD vs. sPD. The performance of the RSs was evaluated with discrimination, calibration, and clinical usefulness.ResultsNo significant difference was found when compared in terms of clinical characteristics of PsP, HPD, and sPD. RS based on combined regions outperformed those from either intra-tumoral or peri-tumoral alone, yielding an AUC (accuracy) of 0.834 (0.827) for PsP vs. HPD, 0.923 (0.868) for PsP vs. sPD, and 0.959 (0.894) for HPD vs. sPD in the training datasets, and 0.835 (0.794) for PsP vs. HPD, 0.919 (0.867) for PsP vs. sPD, and 0.933 (0.842) for HPD vs. sPD in the testing datasets. The combined RS showed good fitness (Hosmer–Lemeshow test p > 0.05) and provided more net benefit than the treat-none or treat-all scheme by decision curve analysis in both training and testing datasets.ConclusionPretreatment radiomics are helpful to predict atypical responses to ICI across tumor types. The combined RS outperformed those from either intra- or peri-tumoral alone which may provide a more comprehensive characterization of atypical responses to ICI.

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Section: Methodssupporting

confidence: 89%

CT-Based Peritumoral and Intratumoral Radiomics as Pretreatment Predictors of Atypical Responses to Immune Checkpoint Inhibitor Across Tumor Types: A Preliminary Multicenter Study

Feng

Lin

et al. 2021

Front. Oncol.

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“…In terms of safety, although the reported AEs were typical for checkpoint blockers, it is concerning that 50% (6/12; 5/7 had AITL) of the patients in our study experienced TTF <2 months and 33% (4/12; 3/4 had AITL) within 1 month. Occurrence of HPD after initiation of immune checkpoint inhibitors (ICI) has been described in the literature in various malignancies ( [21][22][23][24] ). It is important to emphasize that HPD is distinct from pseudoprogression and progression of disease.…”

Section: Discussionmentioning

confidence: 99%

Nivolumab in patients with relapsed or refractory peripheral T-cell lymphoma: modest activity and cases of hyperprogression

Bennani

Kim

Pederson

et al. 2022

J Immunother Cancer

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Peripheral T-cell lymphomas (PTCL), a heterogeneous group of mature aggressive non-Hodgkin’s lymphomas, carry a worse prognosis for most subtypes when compared with their B-cell counterparts. Despite recent approval of newer therapies, the outlook for patients with relapsed/refractory (RR) PTCL remains poor and new treatment strategies are clearly needed. Targeting the profoundly immunosuppressive tumor microenvironment in PTCL is one such approach. To determine whether immune checkpoint blockade targeting program death receptor 1 would be effective in PTCL, we conducted an investigator-initiated phase 2 prospective study of single-agent nivolumab for RR PTCL. We report here results of the pre-specified interim analysis.MethodsThe primary objective was to assess the overall response rate (ORR). Secondary objectives were to assess safety and tolerability of nivolumab in PTCL and to assess progression-free survival (PFS), duration of response (DOR) and overall survival (OS). Hyperprogressive disease (HPD) was defined as time-to-treatment failure of less than or equal to one month from initiation of therapy.ResultsTwelve patients who received at least one cycle of nivolumab were included in this interim analysis. Half (6/12) of the patients had angioimmunoblastic T-cell lymphoma (AITL), 3/12 had PTCL, not otherwise specified. Most (11/12) were advanced stage, had extranodal disease (97.1%) and had received a prior autologous stem cell transplant (50%). The ORR was 33% (95% CI: 12.3 to 63.7%) with two complete response and two partial response. The median PFS was however short at 2.7 months (95% CI: 1.5 to NE); and the median OS was 6.7 months (95% CI: 3.4 to NE). The median DOR was also short at 3.6 months (95% CI: 1.9 to NE). HPD occurred in four patients, three of whom had AITL. Observed grade 3 and higher adverse events (AEs) were non-hematologic in 5/12 (42%), while hematologic AEs were seen in 3/12 (25%).ConclusionsNivolumab had modest clinical activity in R/R PTCL. Due to a high number of hyperprogression and short DOR, a decision was made to halt the study. These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases.Trial registration numberNCT03075553.

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“…A retrospective single site study comparing four selected HPD criteria in their own series of consecutive patients on IO treatments showed the use of the Le Tourneau method to assess HPD to be the preferred one, as it captures adequately this atypical progression and TGK is more convenient to use than TGR. 21 HPD resulted in the clinical deterioration of patients as reflected in shorter PFS and lower likelihoods of receiving additional, salvage therapies, compared with other patients who had disease progression as their best response but no HPD. Worse clinical outcome for patients with HPD compared with patients with natural progressive disease have also been demonstrated in other two studies: one assessing 5 different definitions of HPD in a multicenter cohort series of 405 consecutive patients with lung cancer, 22 and the other one being a systematic review and meta-analysis evaluation of 24 studies including 3109 patients and evaluating all described HPD criteria.…”

Section: Hyperprogression: Unusual Response and Adverse Effect?mentioning

confidence: 99%

iRECIST and atypical patterns of response to immuno-oncology drugs

Ramon-Patino

Schmid

Lau

et al. 2022

J Immunother Cancer

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With the advent of immunotherapy as one of the keystones of the treatment of our patients with cancer, a number of atypical patterns of response to these agents has been identified. These include pseudoprogression, where the tumor initially shows objective growth before decreasing in size, and hyperprogression, hypothesized to be a drug-induced acceleration of the tumor burden. Despite it being >10 years since the first immune-oncology drug was approved, neither the biology behind these paradoxical responses has been well understood, nor their incidence, identification criteria, predictive biomarkers, or clinical impact have been fully described. Immune-based Response Evaluation Criteria in Solid Tumors (iRECIST) guidelines have been published as a revision to the RECIST V.1.1 criteria for use in trials of immunotherapeutics, and the iRECIST subcommittee (of the RECIST Working Group) is working on elucidating these aspects, with data sharing a current major challenge to move forward with this unmet need in immuno-oncology.

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Comparison of radiological criteria for hyperprogressive disease in response to immunotherapy

Cited by 13 publications

References 18 publications

CT-Based Peritumoral and Intratumoral Radiomics as Pretreatment Predictors of Atypical Responses to Immune Checkpoint Inhibitor Across Tumor Types: A Preliminary Multicenter Study

CT-Based Peritumoral and Intratumoral Radiomics as Pretreatment Predictors of Atypical Responses to Immune Checkpoint Inhibitor Across Tumor Types: A Preliminary Multicenter Study

Nivolumab in patients with relapsed or refractory peripheral T-cell lymphoma: modest activity and cases of hyperprogression

iRECIST and atypical patterns of response to immuno-oncology drugs

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