scholarly journals The phenomenon of pseudoprogression in cancer immunotherapy: is everything so unambiguous?

2021 ◽  
Vol 23 (3) ◽  
pp. 496-500
Author(s):  
Vladislav O. Sarzhevskiy ◽  
Vladimir Ia. Melnichenko ◽  
Irina V. Panshina ◽  
Nikita E. Mochkin ◽  
Vladimir S. Bogatyrov ◽  
...  

When evaluating the effect of therapy for malignant neoplasms with inhibitors of CTLA-4, PD-1 and PD-L1, the phenomenon of pseudoprogression may occur. Pseudoprogression is an increase in the volume of tumor tissue due to immunocompetent cells (lymphocytes, macrophages) mobilized into the tumor focus under the action of immunotherapy. As the antitumor effect of lymphocytes and macrophages is realized, the tumor decreases or disappears over time. Pseudoprogression occurs with varying frequency in various types of cancer. It may also matter which immune checkpoint inhibitors is used to treat a solid tumor or lymphoproliferative disease. Currently, several immune-related response-evaluation criteria have been developed, which can help diagnose the phenomenon of pseudoprogression. But, unfortunately, none of these criteria clearly distinguish pseudoprogression from true tumor progression. In the case of an erroneous judgment about the effect of treatment, immunotherapy ends, and the patient may not get a chance for long-term remission. Using two clinical examples (immunotherapy for metastatic kidney cancer and recurrent Hodgkin lymphoma), the authors discuss the pitfalls of evaluating the effectiveness of treatment with checkpoint inhibitors.

2020 ◽  
Vol 13 (1) ◽  
pp. 24-31 ◽  
Author(s):  
Angelo Castello ◽  
Egesta Lopci

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.


Immunotherapy ◽  
2020 ◽  
Vol 12 (18) ◽  
pp. 1303-1312 ◽  
Author(s):  
Maggie Zhou ◽  
Nam Bui ◽  
Shreyana Bolleddu ◽  
Marta Lohman ◽  
Hans-Christoph Becker ◽  
...  

Aim: To analyze the efficacy of checkpoint inhibitors in soft tissue sarcoma. Materials & methods: We retrospectively reviewed patients with advanced soft tissue sarcoma treated with ipilimumab and nivolumab. All patients who received at least one cycle were included. Results: One patient had a complete response and five had a partial response, for an objective response rate of 15%. Clinical benefit rate was 34% with a median duration of 12.0 months (range: 4.5 to 28.9+ months [mo]). Median overall survival was 12.0 months (95% CI: 4.5–23.7+ mo). Median progression-free survival was 2.7 months (95% CI: 2.3–4.5+ mo) by Response Evaluation Criteria in Solid Tumors 1.1 and 2.9 months (2.5–6.0+ mo) by immune-related Response Evaluation Criteria in Solid Tumors. Adverse events of any grade were seen in 58% of patients, the most common being fatigue (21%) and cough (10%), 5% of patients experienced a grade 3 adverse event (AE) (hyperglycemia) or grade 4 AE (myocarditis). Conclusion: Ipilimumab/nivolumab combination showed efficacy and was well tolerated in advanced soft tissue sarcoma.


2021 ◽  
Vol 8 ◽  
Author(s):  
Dong Ho Lee ◽  
Sangyoun Hwang ◽  
Young Hwan Koh ◽  
Kyung-Hun Lee ◽  
Ju Yeon Kim ◽  
...  

Immune response evaluation criteria in solid tumors (iRECIST) is recommended during immune checkpoint inhibitors (ICIs) treatment, due to the possibility of pseudoprogression. We evaluated the frequency of pseudoprogression in hepatocellular carcinoma (HCC) patients. This retrospective multicenter study involved 158 consecutive patients who underwent nivolumab treatment for HCC in Korea. At the initial evaluation, 94 patients presented with immune unconfirmed progressive disease, and 22 continued nivolumab. At the second evaluation, 21 of the 22 patients (95.5%) had confirmed progression and no pseudoprogression was observed. Considering low possibility of pseudoprogression, iRECIST may not be required for HCC.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Inci Kizildag Yirgin ◽  
Sukru Mehmet Erturk ◽  
Izzet Dogan ◽  
Sezai Vatansever

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.


2019 ◽  
Vol 4 ◽  
pp. 21-23
Author(s):  
Purvish M. Parikh ◽  
T. P. Sahoo ◽  
Randeep Singh ◽  
Bahl Ankur ◽  
Talvar Vineet ◽  
...  

Response evaluation criteria in solid tumors (RECIST) are a method used to evaluate and document the response to cancer treatment in solid tumors. The availability of a new class of immuneoncology drugs has resulted in the need to modify RECIST criteria methodology. The first leadership immuno-oncology network (LION) master course brought together experts in oncology and immuno-oncology. Six questions were put to the experts and their opinion, supporting evidence, and experience were discussed to arrive at a practical consensus recommendation. n this nascent field, the availability of a practical consensus recommendation developed by experts in the field is of immense value to the community oncologist and other health-care consultants.


2020 ◽  
Vol 13 (12) ◽  
pp. e236357
Author(s):  
Mary Sessums ◽  
Siva Yarrarapu ◽  
Pramod K Guru ◽  
Devang K Sanghavi

Immune checkpoint inhibitors have revolutionised cancer therapy in the past decade. Although they have been indicated to treat a diverse range of malignant neoplasms, they are also associated with various immune-related adverse effects. We report the case of a 74-year-old man with a history of urothelial carcinoma who had atezolizumab-induced myocarditis and myositis resulting in acute hypercapnic respiratory failure, despite the discontinuation of atezolizumab and aggressive treatment with corticosteroids. This case highlights the importance of a multidisciplinary approach for early diagnosis and treatment of immune-related adverse events. Physicians must be aware of the risks associated with immune checkpoint inhibitors and have a basic knowledge regarding their management.


Author(s):  
Claudia de Wall ◽  
Johann Bauersachs ◽  
Dominik Berliner

AbstractModern treatment strategies have improved prognosis and survival of patients with malignant diseases. The key components of tumor treatment are conventional chemotherapy, radiotherapy, targeted therapies, and immunotherapy. Cardiovascular side-effects may occur in the early phase of tumor therapy or even decades later. Therefore, knowledge and awareness of acute and long-lasting cardiac side effects of anti-cancer therapies are essential. Cardiotoxicity impairs quality of life and overall survival. The new cardiologic subspecialty ‘cardio-oncology’ deals with the different cardiovascular problems arising from tumor treatment and the relationship between cancer and heart diseases. Early detection and treatment of cardiotoxicity is of crucial importance. A detailed cardiac assessment of patients prior to administration of cardiotoxic agents, during and after treatment should be performed in all patients. The current review focusses on acute and long-term cardiotoxic side effects of classical cytotoxic and selected modern drug treatments such as immune checkpoint inhibitors and discusses strategies for the diagnosis of treatment-related adverse cardiovascular effects in cancer patients.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1227.2-1227
Author(s):  
E. Berard ◽  
T. Barnetche ◽  
L. Rouxel ◽  
C. Dutriaux ◽  
L. Dousset ◽  
...  

Background:Description and initial management of rheumatic immune-related adverse-events (irAEs) from cancer immunotherapies have been reported by several groups but to date, few studies have evaluated the long-term outcomes and management of rheumatic irAEs (1).Objectives:To describe the long-term management and assess the one-year outcomes of patients who experienced rheumatic immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI).Methods:This was a single-centre prospective observational study including patients referred for musculoskeletal symptoms while treated with ICI. After baseline rheumatological evaluation defining the clinical entity presented, follow-up visits were organised according to the type and severity of irAE. At one year, persistence of irAE, ongoing treatment, as well as cancer outcomes were assessed.Results:63 patients were included between September 2015 and June 2018. 24 patients (38%) presented with non-inflammatory musculoskeletal conditions managed with short-term symptomatic treatment and did not require specific follow-up. 39 patients (62%) experienced inflammatory manifestations, mimicking either rheumatoid arthritis (RA, n=19), polymyalgia rheumatica (PMR, n=16), psoriatic arthritis (PsA, n=3) and one flare of a preexisting axial spondyloarthritis. Overall, 32 patients (82%) received systemic glucocorticoids, with a median rheumatic dosage of 15mg/day (range: 5-60mg/day). None of the patients had to permanently discontinue ICI therapy for rheumatic irAE. 20 patients (67%) were still receiving glucocorticoids at one year, with a median dosage of 5mg/day (range: 2-20mg/day). Glucocorticoids were more frequently discontinued for patients with RA-like condition (44%) than PMR-like condition (23%), but no other predictive factor of glucocorticoids withdrawal could be identified. At one year, overall survival and progression-free survival were comparable between patients who were still receiving glucocorticoids for rheumatic irAE and patients who have discontinued. Eight patients required csDMARDs.Conclusion:At one year, a majority of patients required long-term low-dose glucocorticoids for chronic rheumatic irAE, which seems not altering oncological control.References:[1]Braaten TJ, Brahmer JR, Forde PM, et al. Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation. Ann Rheum Dis. 2019 Sep 20.Disclosure of Interests:None declared


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