scholarly journals Are radiologists ready to evaluate true response to immunotherapy?

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Inci Kizildag Yirgin ◽  
Sukru Mehmet Erturk ◽  
Izzet Dogan ◽  
Sezai Vatansever
Keyword(s):  
Tumor Response ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Evaluation Criteria ◽  
Response Assessment ◽  
Radiological Imaging ◽  
Response Evaluation ◽  
Medical Oncologists ◽  
Cell Death Protein ◽  
Optimal Patient Management

Abstract Background Standardized response criteria for evaluating patients radiological imaging have an essential role in oncological management. Immunotherapy, using immune checkpoint inhibitors (ICIs), including drugs targeting cytotoxic T-lymphocyte-associated antigen 4 and programmed cell death protein 1 or its ligand, promise a new role that has demonstrated improvement management in cancers resistant to chemotherapy. This article reviews the literature to understand the most useful response evaluation criteria for optimal patient management under immunotherapy treatment. Areas that warrant further research are described. Conclusion In conclusion, ICIs have become more widely accepted and used by medical oncologists. Radiologists face challenges in assessing tumor response and becoming more involved in the management of treatment. The latest published immune-RECIST criteria can be used in response assessment, but further prospective evaluation is needed with registration clinical trials to be definitively validated.

Tumor Response Assessment for Precision Cancer Therapy: Response Evaluation Criteria in Solid Tumors and Beyond

2018 ◽  
pp. 1019-1029 ◽  
Author(s):  
Mizuki Nishino
Keyword(s):  
Cancer Therapy ◽  
Solid Tumors ◽  
Tumor Response ◽  
Objective Assessment ◽  
Evaluation Criteria ◽  
Therapy Response ◽  
Response Assessment ◽  
Cancer Therapies ◽  
Response Evaluation ◽  
Response Evaluation Criteria

Objective assessment of tumor responses and treatment results has been the basis for the advancement of cancer therapies, and imaging plays a key role to provide a “common language” to describe the results of cancer treatment. Although Response Evaluation Criteria in Solid Tumors (RECIST) has been the most widely accepted method for assessing tumor response in the past decades, the limitations of RECIST have increasingly becoming recognized, especially with the recent advances of precision-medicine approaches to cancer. This article reviews the current concept of tumor response evaluations based on RECIST, describes the limitations of RECIST, and proposes strategies to overcome the limitations. The article emphasizes specific limitations in the setting of precision cancer therapy and cancer immunotherapy and discusses the important insights provided by the cutting-edge investigations in the emerging fields.

Assessing solid tumor response with and without RECIST.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 504-504
Author(s):  
Aileen Deng ◽  
Benjamin E Leiby ◽  
Russell J. Schilder ◽  
William Kevin Kelly ◽  
Sandeep Deshmukh ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Progressive Disease ◽  
Tumor Response ◽  
Evaluation Criteria ◽  
Kappa Statistic ◽  
Response Assessment ◽  
Complete Response ◽  
Response Evaluation ◽  
Academic Center ◽  
Standard Report

504 Background: Response Evaluation Criteria in Solid Tumors (RECIST) has become widely accepted as gold standard for response evaluation in clinical trials. It remains underutilized in routine clinical practice. We compared tumor response assessment made with and without RECIST. Methods: This study included patients with solid tumors who underwent imaging from January 2013 to December 2014 at a single academic center. Tumor response was assessed by a radiologist using RECIST and by an oncologist (Onc) and resident (Res) without using RECIST (standard report). Tumor response was classified as progressive disease (PD), stable disease (SD), partial response (PR) and complete response (CR). Agreement in assessment between RECIST and standard report was determined by percent agreement and Kappa statistic. Results: 292 imaging studies were included. Concordance between RECIST and Onc-interpreted standard report is presented in Table 1. Overall agreement between RECIST and Onc-interpreted standard report was 56% (95% CI: 46-65%) and Kappa was 0.31 (95% CI: 0.19-0.44). Similar results were seen between RECIST and Res-interpreted standard report (Table 1). Overall agreement between RECIST and Res-interpreted report was 54% (95% CI: 44%-63%) and Kappa was 0.26 (95% CI: 0.13-0.40). Conclusions: Our study found variability in tumor response assessment between clinicians and radiologists. RECIST-classified PD was often interpreted as SD and vice versa, a distinction that affect treatment decisions. Our study highlights the need to standardize tumor response assessment. [Table: see text]

The Role of PET/CT in the Era of Immune Checkpoint Inhibitors: State of Art

2020 ◽  
Vol 13 (1) ◽  
pp. 24-31 ◽  
Author(s):  
Angelo Castello ◽  
Egesta Lopci
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Evaluation Criteria ◽  
Advanced Melanoma ◽  
Response Criteria ◽  
Response Evaluation ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

Background: Immune checkpoint inhibitors (ICI) have achieved astonishing results and improved overall survival (OS) in several types of malignancies, including advanced melanoma. However, due to a peculiar type of anti-cancer activity provided by these drugs, the response patterns during ICI treatment are completely different from that with “old” chemotherapeutic agents. Objective: To provide an overview of the available literature and potentials of 18F-FDG PET/CT in advanced melanoma during the course of therapy with ICI in the context of treatment response evaluation. Methods: Morphologic criteria, expressed by Response Evaluation Criteria in Solid Tumors (RECIST), immune-related response criteria (irRC), irRECIST, and, more recently, immune-RECIST (iRECIST), along with response criteria based on the metabolic parameters with 18F-Fluorodeoxyglucose (18FFDG), have been explored. Results: To overcome the limits of traditional response criteria, new metabolic response criteria have been introduced on time and are being continuously updated, such as the PET/CT Criteria for the early prediction of Response to Immune checkpoint inhibitor Therapy (PECRIT), the PET Response Evaluation Criteria for Immunotherapy (PERCIMT), and “immunotherapy-modified” PET Response Criteria in Solid Tumors (imPERCIST). The introduction of new PET radiotracers, based on monoclonal antibodies combined with radioactive elements (“immune-PET”), are of great interest. Conclusion: Although the role of 18F-FDG PET/CT in malignant melanoma has been widely validated for detecting distant metastases and recurrences, evidences in course of ICI are still scarce and larger multicenter clinical trials are needed.

scholarly journals Rheumatic immune-related adverse events from checkpoint inhibitor therapy: a case series

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Antonella Laria ◽  
Alfredomaria Lurati ◽  
Laura Castelnovo ◽  
Antonio Tamburello ◽  
Paola Maria Faggioli ◽  
...  
Keyword(s):  
Adverse Events ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Hematologic Malignancies ◽  
Checkpoint Inhibitor Therapy ◽  
Cancer Immunotherapies ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and its ligand PD-L1 are established cancer immunotherapies for solid tumor and hematologic malignancies. These therapies are involved in immune-related adverse events (irAE), both general and rheumatic ones. In general, immune-related adverse events (irAE) management includes drug-holding, tapering doses of corticosteroids, and specific immunosuppression for clinically severe cases, such as infliximab or mycophenolate.

The evolving landscape of criteria for evaluating tumor response in the era of cancer immunotherapy: From Karnofsky to iRECIST

2018 ◽  
Vol 104 (2) ◽  
pp. 88-95 ◽  
Author(s):  
Alessandro Inno ◽  
Giuseppe Lo Russo ◽  
Matteo Salgarello ◽  
Giulia Corrao ◽  
Raffaella Casolino ◽  
...  
Keyword(s):  
Tumor Response ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Therapy Response ◽  
Clinical Activity ◽  
Special Focus ◽  
Response Evaluation ◽  
Recist 1.1 ◽  
New Anticancer Drugs ◽  
Response Evaluation Criteria

The objective response is an important endpoint to evaluate clinical activity of new anticancer drugs. Standardized criteria for evaluating response are needed for comparing results of different trials and represent the basis for advances in cancer therapy. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 are the most used in clinical practice and in clinical trials; however, they are not able to capture atypical responses seen with immunotherapy drugs. We describe the evolution of response criteria with a special focus on the immune-related criteria.

Difficulties in differentiating between checkpoint inhibitor pneumonitis and lung metastasis in a patient with melanoma

Immunotherapy ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 293-298 ◽  
Author(s):  
Houssein Safa ◽  
Priya Bhosale ◽  
Annika Weissferdt ◽  
Isabella C Glitza Oliva
Keyword(s):  
Clinical Presentation ◽  
Cytotoxic T Lymphocyte ◽  
Late Onset ◽  
Checkpoint Inhibitors ◽  
Lung Nodule ◽  
Complete Response ◽  
Lung Lesions ◽  
Discontinuation Of Treatment ◽  
Cell Death Protein ◽  
New Onset

The use of immune checkpoint inhibitors is associated with significant toxicities such as pneumonitis; the clinical presentation of the latter can be misleading and may mimic metastasis. We report the case of a melanoma patient who developed late-onset pneumonitis after discontinuation of treatment with anti-programmed cell death protein 1 (PD1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA4) (patient had a complete response). The patient was asymptomatic, however, surveillance computed tomography (CT) scan showed a growing lung nodule and several new-onset, small lung lesions highly suspicious for recurrence. A biopsy of the lesions revealed organizing pneumonia with absence of malignant cells. The lung lesions completely resolved after 6 months without any intervention. The patient is still in complete remission 2 years after the initial diagnosis of melanoma.

A novel morphologic and metabolic feature fused treatment response evaluation pipeline for pancreatic adenocarcinoma patients.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 311-311
Author(s):  
Yi Lao ◽  
John David ◽  
Arman Torosian ◽  
Wensha Yang ◽  
Richard Tuli
Keyword(s):  
Treatment Response ◽  
Pancreatic Adenocarcinoma ◽  
Tumor Response ◽  
Locally Advanced ◽  
Standardized Uptake Value ◽  
Predictive Marker ◽  
Response Assessment ◽  
Surface Registration ◽  
Response Evaluation ◽  
Pet Ct

311 Background: Adaptive radiation therapy for pancreatic adenocarcinoma (PA) relies on accurate treatment response assessment. Traditional RECIST criteria poorly characterize tumors with complex morphological features, while PET imaging inefficiently detects tumors with intrinsically low standardized uptake value (SUV). Here, we performed regional comparisons of 3D intact PA surfaces pre and post chemoradiotherapy (CRT) utilizing surface measurements containing both morphological and metabolic features to better assess response. Methods: Twenty-one locally advanced PA patients with pre- and 6-8 week post-CRT 18F FDG-PET/CT scans were evaluated. Boundaries of initial and post-CRT tumors were manually defined on respective CT images. On each of the tumors, 3D meshes were generated, followed by surface based registration to achieve vertex-wise correspondence. For each surface vertex, a multivariate vector was formed from two components: anatomic (deformation tensors resulted from surface registration), and metabolic (regional SUV obtained from radius to surface projections). To assess tumor response, paired mahabanobis distance (Mdist) between pre- and post-CRT tumor surfaces with previously formed multivariate vectors were calculated for each patient. Mdist was evaluated using Cox analysis correlated with overall survival (OS) and compared with measurements based on serum CA19-9, volume, SUVmax and SUVmean. Results: Among all the tested parameters, Mdist is the best predictor of OS, with a hazard ratio of 0.437 (p = 0.036). Post-CRT versus pre-CRT ratios based on volume and SUVmax both reached borderline significance (p = 0.0769 and 0.0799, respectively), while CA19-9 and SUVmean failed in predicting OS in our small cohort of patients. Conclusions: We introduced a PET/CT-based novel morphologic and metabolic pipeline for post-CRT response evaluation in locally advanced PA. The fused Mdist outperformed traditional morphologic, metabolic, and physiological measurements in OS prediction. The presented fused model may serve as a new biomarker to better characterize the heterogeneity of tumor response to CRT and a predictive marker for surgical resection.

Autoimmune complications of immunotherapy: pathophysiology and management

BMJ ◽  
2020 ◽  
pp. m736 ◽  
Author(s):  
Karmela K Chan ◽  
Anne R Bass
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Case Fatality ◽  
High Grade ◽  
Almost All ◽  
Inhibitory Molecules ◽  
Patients Experience ◽  
Cell Death Protein

Abstract Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or its ligand, programmed cell death protein ligand 1 (PD-L1), and lead to immune activation in the tumor micro-environment. ICIs can induce durable treatment responses in patients with advanced cancers, but they are commonly associated with immune related adverse events (irAEs) such as rash, colitis, hepatitis, pneumonitis, and endocrine and musculoskeletal disorders. Almost all patients experience some form of irAE, but high grade irAEs occur in approximately half of those on combination therapy (eg, anti-CTLA-4 plus anti-PD-1), and up to one quarter receiving ICI monotherapy. Fatal irAEs occur in approximately 1.2% of patients on CTLA-4 blockade and 0.4% of patients receiving PD-1 or PD-L1 blockade, and case fatality rates are highest for myocarditis and myositis. IrAEs typically occur in the first three months after ICI initiation, but can occur as early as one day after the first dose to years after ICI initiation. The mainstay of treatment is with corticosteroids, but tumor necrosis factor inhibitors are commonly used for refractory irAEs. Although ICIs are generally discontinued when high grade irAEs occur, ICI discontinuation alone is rarely adequate to resolve irAEs. Consensus guidelines have been published to help guide management, but will likely be modified as our understanding of irAEs grows.

scholarly journals The Evaluation of Response to Immunotherapy in Metastatic Renal Cell Carcinoma: Open Challenges in the Clinical Practice

2019 ◽  
Vol 20 (17) ◽  
pp. 4263 ◽  
Author(s):  
Alessandra Raimondi ◽  
Giovanni Randon ◽  
Pierangela Sepe ◽  
Melanie Claps ◽  
Elena Verzoni ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Practice ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Evaluation Criteria ◽  
Death Receptor ◽  
Response Assessment ◽  
Disease Response

Immunotherapy has changed the therapeutic scenario of metastatic renal cell carcinoma (mRCC), however the evaluation of disease response to immune-checkpoint inhibitors is still an open challenge. Response evaluation criteria in solid tumors (RECIST) 1.1 criteria are the cornerstone of response assessment to anti-neoplastic treatments, but the use of anti-programmed death receptor 1 (PD1) and other immunotherapeutic agents has shown atypical patterns of response such as pseudoprogression. Therefore, immune-modified criteria have been developed in order to more accurately categorize the disease response, even though their use in the everyday clinical practice is still limited. In this review we summarize the available evidence on this topic, with particular focus on the application of immune-modified criteria in the setting of mRCC.

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