CT radiomics compared to a clinical model for predicting checkpoint inhibitor treatment outcomes in patients with advanced melanoma.

INTRODUCTION: Predicting checkpoint inhibitors treatment outcomes in melanoma is a relevant task, due to the unpredictable and potentially fatal toxicity and high costs for society. However, accurate biomarkers for treatment outcomes are lacking. Radiomics are a technique to quantitatively capture tumour characteristics on readily available computed tomography (CT) imaging. The purpose of this study was to investigate the added value of radiomics for predicting clinical benefit from checkpoint inhibitors in melanoma in a large, multicenter cohort. METHODS: Patients who received first-line anti-PD1±anti-CTLA4 treatment for advanced cutaneous melanoma were retrospectively identified from nine participating hospitals. For every patient, up to five representative lesions were segmented on baseline CT, and radiomics features were extracted. A machine learning pipeline was trained on the radiomics features to predict clinical benefit, defined as stable disease for more than 6 months or response per RECIST 1.1 criteria. This approach was evaluated using a leave-one-centre-out cross validation and compared to a model based on previously discovered clinical predictors. Lastly, a combination model was built on the radiomics and clinical model. RESULTS: A total of 620 patients were included, of which 59.2% experienced clinical benefit. The radiomics model achieved an area under the receiver operator characteristic curve (AUROC) of 0.607 [95% CI, 0.562-0.652], lower than that of the clinical model (AUROC=0.646 [95% CI, 0.600-0.692]). The combination model yielded no improvement over the clinical model in terms of discrimination (AUROC=0.636 [95% CI, 0.592-0.680]) or calibration. The output of the radiomics model was significantly correlated with three out of five input variables of the clinical model (p < 0.001). DISCUSSION: The radiomics model achieved a moderate predictive value of clinical benefit, which was statistically significant. However, a radiomics approach was unable to add value to a simpler clinical model, most likely due to the overlap in predictive information learned by both models. Future research should focus on the application of deep learning, spectral CT-derived radiomics, and a multimodal approach for accurately predicting benefit to checkpoint inhibitor treatment in advanced melanoma.

Imaging to predict checkpoint inhibitor outcomes in cancer. A systematic review.

BACKGROUND: Checkpoint inhibition has radically improved the perspective for patients with metastatic cancer, but predicting who will not respond with high certainty remains difficult. Imaging-derived biomarkers may be able to provide additional insights into the heterogeneity in tumour response between patients. In this systematic review, we aimed to summarise and qualitatively assess the current evidence on imaging biomarkers that predict response and survival in patients treated with checkpoint inhibitors in all cancer types. METHODS: PubMed and Embase were searched from database inception to 29th November 2021. Articles eligible for inclusion described baseline imaging predictive factors, radiomics and/or imaging machine learning models for predicting response and survival in patients with any kind of malignancy treated with checkpoint inhibitors. Risk of bias was assessed using the QUIPS and PROBAST tools and data was extracted. RESULTS: In total, 119 studies including 15,580 patients were selected. Of these studies, 73 investigated simple imaging factors. 45 studies investigated radiomic features or deep learning models. Predictors of worse survival were (i) higher tumour burden, (ii) presence of liver metastases, (iii) less subcutaneous adipose tissue, (iv) less dense muscle and (v) presence of symptomatic brain metastases. Hazard rate ratios did not exceed 2.00 for any predictor in the larger and higher quality studies. The added value of baseline fluorodeoxyglucose positron emission tomography parameters in predicting response to treatment was limited. Pilot studies of radioactive drug tracer imaging showed promising results. Reports on radiomics were almost unanimously positive, but numerous methodological concerns exist. CONCLUSIONS: There is well-supported evidence for several imaging biomarkers that can be used in clinical decision making. Further research, however, is needed into biomarkers that can more accurately identify which patients who will not benefit from checkpoint inhibition. Radiomics and radioactive drug labelling appear to be promising approaches for this purpose.