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Case Series: Abscopal Benefit of Surgery in 3 Immunotherapy-Treated Patients With Unresectable Cancer.

ABSTRACT: For all of the optimism that immunotherapy has engendered, the flip side is that 7/10 patients with susceptible tumor types do not respond, while in nonsusceptible tumor types the response rates are significantly lower. In contradiction of the current orthodoxy against surgery in the setting of unresectable disease, we present 3 examples of immunotherapy-treated patients with widespread recurrence who experienced dramatic clinical improvement following debulking/metastasectomy. Taken together with examples from the literature that correlate longer survival with surgical intervention during treatment with immunotherapy, these 3 cases suggest that a new paradigm involving a wider role for surgery in the management of these patients should be explored. Possible mechanisms by which surgery may synergize with immunotherapy and improve outcomes are also discussed.

SUBMITTER: Oronsky B

PROVIDER: S-EPMC6069027 | biostudies-literature | 2018 Jan-Dec

REPOSITORIES: biostudies-literature

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Case Series: Abscopal Benefit of Surgery in 3 Immunotherapy-Treated Patients With Unresectable Cancer.

Oronsky Bryan B Larson Chris C Reid Tony R TR Carter Corey A CA

Journal of investigative medicine high impact case reports 20180101

For all of the optimism that immunotherapy has engendered, the flip side is that 7/10 patients with susceptible tumor types do not respond, while in nonsusceptible tumor types the response rates are significantly lower. In contradiction of the current orthodoxy against surgery in the setting of unresectable disease, we present 3 examples of immunotherapy-treated patients with widespread recurrence who experienced dramatic clinical improvement following debulking/metastasectomy. Taken together wi ...[more]

PMID: 30083560

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Project description:BACKGROUND:Combining radiotherapy (RT) with immuno-oncology (IO) therapy (IORT) may enhance IO-induced antitumor response. Quantitative imaging biomarkers can be used to provide prognosis, predict tumor response in a non-invasive fashion and improve patient selection for IORT. A biologically inspired CD8 T-cells-associated radiomics signature has been developed on previous cohorts. We evaluated here whether this CD8 radiomic signature is associated with lesion response, whether it may help to assess disease spatial heterogeneity for predicting outcomes of patients treated with IORT. We also evaluated differences between irradiated and non-irradiated lesions. METHODS:Clinical data from patients with advanced solid tumors in six independent clinical studies of IORT were investigated. Immunotherapy consisted of 4 different drugs (antiprogrammed death-ligand 1 or anticytotoxic T-lymphocyte-associated protein 4 in monotherapy). Most patients received stereotactic RT to one lesion. Irradiated and non-irradiated lesions were delineated from baseline and the first evaluation CT scans. Radiomic features were extracted from contrast-enhanced CT images and the CD8 radiomics signature was applied. A responding lesion was defined by a decrease in lesion size of at least 30%. Dispersion metrices of the radiomics signature were estimated to evaluate the impact of tumor heterogeneity in patient's response. RESULTS:A total of 94 patients involving multiple lesions (100 irradiated and 189 non-irradiated lesions) were considered for a statistical interpretation. Lesions with high CD8 radiomics score at baseline were associated with significantly higher tumor response (area under the receiving operating characteristic curve (AUC)=0.63, p=0.0020). Entropy of the radiomics scores distribution on all lesions was shown to be associated with progression-free survival (HR=1.67, p=0.040), out-of-field abscopal response (AUC=0.70, p=0.014) and overall survival (HR=2.08, p=0.023), which remained significant in a multivariate analysis including clinical and biological variables. CONCLUSIONS:These results enhance the predictive value of the biologically inspired CD8 radiomics score and suggests that tumor heterogeneity should be systematically considered in patients treated with IORT. This CD8 radiomics signature may help select patients who are most likely to benefit from IORT.

Dataset Information

Case Series: Abscopal Benefit of Surgery in 3 Immunotherapy-Treated Patients With Unresectable Cancer.

Publications

Case Series: Abscopal Benefit of Surgery in 3 Immunotherapy-Treated Patients With Unresectable Cancer.

Similar Datasets

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