| Objective:To investigate the strategy of immune-related adverse events(ir AEs)incidence of patients with lung cancer after PD1/PD-L1 inhbititrs therapy,explore on new radiological assessments for immunotherapy response and abnormal radiological responses(hyperprogression,dissociative responses,and pseudoprogression).Methodology:Performed a systematic search and meta-analysis on"Pub Med/Medline,Web of Science,Science Direct,and Scopus"to identify studies reporting about changes in clinical imaging-related indexes after PD-1/PD-L1 treatment of LC.The search period covered was from 2011-2021;Studies were published in English.We conducted the research conducted on 15 October 2021.Literature Identification was achieved using different search terms,including"PD1-PD-L1 treatment of lung cancer,immune checkpoint inhibitors,programmed cell death 1,non-small cell lung cancer,programmed cell death ligand 1,Imaging and treatment-related adverse effects"research method were("Imaging OR Radiology OR CT"and"adverse events OR ir AEs"and"PD-1inhibitors OR PD-1 treatment"and Lung cancer).Because we intended to analyze the ir AEs appearances of patients with lung cancer in this study,only studies meeting the following criteria were included in the analysis:original research studies reported clinical characteristics and imaging features of lung cancer patients.Studies included at least ten patients,and studies were published in English literature.Isolated case reports or case series with a sample size of less than 10 were excluded due to the low level of evidence.We also excluded editorials,opinions,commentaries,and other types of publications.There is no reference in the literature on drug doses so can not be used as an exclusion criterion.We assessed the relevant studies(titles,abstracts,and full-text).They extracted the following information from each study for the analysis of imaging findings:the number of patients enrolled;mean/or median age and sex of participants;lesion distribution in;typical abnormalities including consolidation and ground-glass opacities(GGO);and less common findings including a crazy-paving pattern,patchy shadow,air bronchogram,linear opacities,bronchiectasis or bronchial wall thickening,pleural effusion,and vascular enhancement,and others.We also analyzed the diagnostic value of CT or CXR in the diagnostic assessment of lung cancer if the studies’data were available Furthermore,the level of involvement in lesion distribution and the number of affected organs were analyzed when the information was available.Meta-analysis was conducted using R–Statistical Software,Risk of Bias Assessment used New Castle Ottawa.We Studied the prevalence of adverse effects related to radiologic findings for patients who received treatment with PD-1,and PD-L1 inhibitors were using dichotomus Data(events,total)In the literature extracted,the occurrence and incidence of severity ranked the immune-related adverse events.Group frontline and subsequent group therapy were estimated as the number of observed follow-ups divided by the person-time follow-up—the prevalence and95%corresponding CI-rated meta-analysis.Heterogeneity is evaluated with the Chi~2testing and I~2statistic,P value less than 0.05indicates significant heterogeneity,I~2value greater than 50%is considered considerable heterogeneityResults:Baseline characteristics of the studies selected were grouped according to the author and year of publishing,the number of patients who received first-line ICI and those who received subsequent line ICI treatment,the median age for each group,type of therapy used such as nivolumab,pembrolizumab,and duration of follow up that was measured in weeks.The incidence of ir AEs was more prevalent in patients receiving first-line treatment at P<0.001 in both high and low-grade ir AEs than those receiving subsequent therapy.The most common ir AEs in the clinical studies were Pneumonitis,Colitis,hypothyroidism,hyperthyroidism,and lesion or skin reactions.Less common ir AEs were hepatitis.In one study,patients were excluded due to the development of CIP.Three studies had patients treated with nivolumab,with three patients developing nivolumab-related cholangitis.One study had patients developing exertional dyspnea four months after taking pembrolizumab.One study had patients who developed ir AEs other than sarcoidosis.Inclusion criteria also involved single-arm or randomized trials evaluating PD-1 and PD-L1inhibitors as a single agent in NSCLC and data on overall response rate(ORR)progression-free survival(PFS)in patients with positive PD-L1 expression(defined as>1%tumor or immune cell PD-L1expression).All imaging studies were performed after nivolumab discontinuation and,before starting the subsequent therapy,were included as PD-1 inhibitors as ir AEs can occur months or even years after treatment discontinuation.Outcomes were grouped into two results,primary and secondary.One study example had patients developing ir AEs that were radiologically notable with an average onset time of about seven weeks.noted Pneumonitis and Colitis,presenting as pancolitis and diverticulosis-related segmental Colitis.Patterns included acute interstitial pneumonia(AIP)/acute respiratory distress syndrome(ARDS)and cryptogenic organizing pneumonia(COP)pattern.Other ir AEs in the study were enteritis(inflammation of the small intestine),thyroiditis,hepatitis,and pancreatitis.Age and prior treatment with radiotherapy were also determinant factors in the overall association with ir AEs.Immune-related adverse events occurred in all studies,with one study indicating a worrisome incidence of checkpoint inhibitor pneumonitis.Conclusion1.The proper assessment of radiological outcomes during and after ICIs therapies is critical in both experimental and clinical settings,different response criteria(IRC,ir RECIST,and i RECIST)have been proposed and utilized in immunotherapy clinical research throughout the years.2.abnormal Radiological responses occur in lung cancer patients with immunotherapy;therefore,the clinical benefit with those patients could be underestimated since paradoxical or dissociated responses,and the pseudoprogression phenomena,radiologists must be aware of aberrant tumor responses and the extensive adverse outcomes associated with imaging in immun-otherapy patients.3.The study showed ir AEs in patients treated with PD-1/PD-L1inhibitors and in patients who were treated with a combination of CTLA-4 inhibitors.Pneumonitis and Colitis were most prevalent,while old age and a history of radiotherapy made patients in those groups more susceptible to developing ir AEs.4.Consistent CT scans,education for both clinicians and patients,and early detection of symptoms for accurate and fast diagnosis are the key factors to managing and treating ir AEs.5.Immunotherapy has been a groundbreaking form of cancer treatment and the more the side effects are understood,the better clinicians especially Radiologists can be prepared to deal with them.6.The increasing use of Immune checkpoint inhibitors increased the need for radiological Competencies to clarify immune-related Side effects.All in paper includes 9 figures,4 tables and 60 references. |
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