Role of medical imaging for immune checkpoint blockade therapy: From response assessment to prognosis prediction

Wei, Hong; Jiang, Hanyu; Song, Bin

doi:10.1002/cam4.2464

Cited by 16 publications

(11 citation statements)

References 93 publications

(290 reference statements)

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“…With the expanded use of immunotherapy, systemic toxicity is a particularly important issue. The development of optimal imaging tools to detect irAEs will increase the detection of these events and improve their management 148 . The identification of biomarkers for variations in gastrointestinal flora, cytokine profiles, and neutrophil activation could enable the identification of populations at higher risk for development of irAEs 117,149‐151 …”

Section: Precision Medicine: Targeted Therapy and Immunotherapymentioning

confidence: 99%

Blueprint for cancer research: Critical gaps and opportunities

Elmore

Greer

Daniels

et al. 2020

CA A Cancer J Clinicians

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We are experiencing a revolution in cancer. Advances in screening, targeted and immune therapies, big data, computational methodologies, and significant new knowledge of cancer biology are transforming the ways in which we prevent, detect, diagnose, treat, and survive cancer. These advances are enabling durable progress in the goal to achieve personalized cancer care. Despite these gains, more work is needed to develop better tools and strategies to limit cancer as a major health concern. One persistent gap is the inconsistent coordination among researchers and caregivers to implement evidence‐based programs that rely on a fuller understanding of the molecular, cellular, and systems biology mechanisms underpinning different types of cancer. Here, the authors integrate conversations with over 90 leading cancer experts to highlight current challenges, encourage a robust and diverse national research portfolio, and capture timely opportunities to advance evidence‐based approaches for all patients with cancer and for all communities.

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Section: Precision Medicine: Targeted Therapy and Immunotherapymentioning

confidence: 99%

Blueprint for cancer research: Critical gaps and opportunities

Elmore

Greer

Daniels

et al. 2020

CA A Cancer J Clinicians

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“…This is due to atypical response patterns such as the associated inflammatory response that can cause an increase in tumor volume, i.e., pseudo-progression [5][6][7]. To account for this, immune-related response assessment systems (irRC, irRECIST, iRECIST) for evaluation of response to immunotherapy have been implemented [8]. However, these modified criteria are merely related to tumor size and limited for early assessment of treatment response [5,9].…”

Section: Introductionmentioning

confidence: 99%

Monitoring CD8a+ T Cell Responses to Radiotherapy and CTLA-4 Blockade Using [64Cu]NOTA-CD8a PET Imaging

et al. 2020

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Purpose: Current response assessment systems for cancer patients receiving immunotherapy are limited. This is due to the associated inflammatory response that may confound the conventional morphological response evaluation criteria in solid tumors and metabolic positron emission tomography (PET) response criteria in solid. Recently, novel PET imaging techniques using radiolabeled antibodies and fragments have emerged as a particularly sensitive and specific modality for quantitative tracking of immune cell dynamics. Therefore, we sought to investigate the utility of Cu-64 labeled F(ab)′2 fragments for in vivo detection of CD8a + T cells as a prognostic imaging biomarker of response to immunotherapy in an immunocompetent mouse model of colorectal cancer. Procedures: [ 64 Cu]NOTA-CD8a was produced by enzymatic digestion of rat-anti-mouse CD8a antibody (clone YTS169.4), purified yielding isolated CD8a-F(ab)′2 fragments and randomly conjugated with the 2-S-(isothiocyanatbenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) chelator. NOTA-CD8a was radiolabeled with Cu-64 and injected into CT26 tumor-bearing mice for longitudinal assessment. To investigate the value of [ 64 Cu]NOTA-CD8a PET imaging for assessment of treatment response, CT26 tumor-bearing mice were subjected to external radiation therapy (XRT) in combination with anti-CTLA-4 therapy. Imaging data was supported by flow cytometry and immunohistochemistry (IHC). Results: Combination treatment with XRT and anti-CTLA-4 effectively inhibited tumor growth until day 22 post-therapy initiation (p = 0.0025) and increased the overall survival of mice compared to control (p = 0.0017). The [ 64 Cu]NOTA-CD8a tumor-to-heart ratio was increased in XRT + anti-CTLA-4-treated mice on day 8 after initiation of therapy (p = 0.0246). Flow cytometry and IHC confirmed the increase in tumor-infiltrating CD8a + cells in XRT + anti-CTLA-4-treated mice. Furthermore, [ 64 Cu]NOTA-CD8a PET imaging distinguished responders and nonresponders prior to treatment-induced changes in tumor volume among mice. Conclusion: In the present study, we demonstrated that [ 64 Cu]NOTA-CD8a was able to detect treatment-induced changes in CD8a + infiltration in murine CT26 colon tumors following a common preclinical combination treatment protocol. Overall, [ 64 Cu]NOTA-CD8a exhibited good prognostic and predictive value. We suggest that [ 64 Cu]NOTA-CD8a PET imaging can be used as an early biomarker of response to therapy in preclinical models.

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“…This will undoubtedly be challenging as radiographic response patterns can be quite variable for tumors treated with immunotherapy. Specifically, immunotherapies can lead to a phenomenon known as “pseudoprogression,” where there is initial radiographic progression followed by a response or stabilization [ 8 ]. Because the standard RECIST criteria would not apply to this tumor response pattern, other imaging modalities have been studied.…”

Section: Discussionmentioning

confidence: 99%

Pathologic Complete Response to Neoadjuvant Nivolumab/Ipilimumab in a Patient with Metastatic Renal Cell Carcinoma

Peak

Fenu

Rothberg

et al. 2020

Case Reports in Urology

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Nivolumab plus ipilimumab represents an effective combination of checkpoint inhibitors that can lead to a durable response with minimal toxicity in patients with metastatic renal cell carcinoma (mRCC). We present a case of a pathologic complete response to neoadjuvant nivolumab plus ipilimumab in a patient with a 13.9 cm left renal mass and significant retroperitoneal and iliac lymphadenopathy, classified as intermediate-risk mRCC. We discuss and review the literature on complete responses after systemic therapy and the ability to predict who has undergone a complete response in the face of residual radiographic evidence of disease.

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Role of medical imaging for immune checkpoint blockade therapy: From response assessment to prognosis prediction

Cited by 16 publications

References 93 publications

Blueprint for cancer research: Critical gaps and opportunities

Blueprint for cancer research: Critical gaps and opportunities

Monitoring CD8a+ T Cell Responses to Radiotherapy and CTLA-4 Blockade Using [64Cu]NOTA-CD8a PET Imaging

Pathologic Complete Response to Neoadjuvant Nivolumab/Ipilimumab in a Patient with Metastatic Renal Cell Carcinoma

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