Radiologic Pseudoprogression during Anti-PD-1 Therapy for Advanced Non-Small Cell Lung Cancer.

Anti-programmed cell death protein 1 (PD-1) therapy can lead to unconventional tumor responses, including radiologic pseudoprogression. Here we have determined the real-world incidence of radiologic pseudoprogression in advanced NSCLC and compared radiologic response criteria for assessment of disease response. The electronic medical records of all patients with NSCLC who were receiving anti-PD-1 therapy at our institution over a 3-year period were retrospectively reviewed, and patients with clinically suspected radiologic pseudoprogression were identified. Patients without available follow-up imaging or clinical data were excluded. Imaging examinations were then analyzed to determine whether progression was confirmed on subsequent reimaging. Assessments of tumor response by the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (RECIST 1.1), the unidimensional immune-related response criteria (iRRC), and the iRECIST criteria for all patients were performed and compared. A total of 228 consecutive patients began receiving anti-PD-1 therapy over a 3-year period. Of the 166 of these patients who were evaluable, most (80%) received nivolumab. Fifteen patients (9%) were clinically suspected of having radiologic pseudoprogression on account of tumor enlargement and/or development of new lesions on computed tomography images during the first 4 to 6 weeks of therapy, and they continued receiving anti-PD-1 therapy. Three of these patients (2%) demonstrated evidence of radiologic pseudoprogression at first reimaging. The iRRC and immune RECIST criteria were more accurate in classifying radiologic pseudoprogression as nonprogression; none of the three cases were deemed progression by the iRRC or immune RECIST, whereas all three cases were determined to be progression according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Radiologic pseudoprogression is a clinical challenge but an uncommon occurrence in patients with NSCLC who are receiving anti-PD-1 therapy.

Katz SI ，Hammer M ，Bagley SJ ，Aggarwal C ，Bauml JM ，Thompson JC ，Nachiappan AC ，Simone CB 2nd ，Langer CJ ... -  《-》

Thoracic Imaging of Non-Small Cell Lung Cancer Treated With Anti-programmed Death Receptor-1 Therapy.

Treatment with anti-programmed death receptor-1 (PD-1) therapeutics can lead to unconventional responses and side effect profiles due to their potentiating effects on the immune system. Here we evaluate the radiologic manifestations of anti-PD-1 therapy in the chest in patients with non-small cell lung cancer (NSCLC) receiving anti-PD-1 therapy. A retrospective review of real-world clinical practice was conducted of all the patients with NSCLC receiving anti-PD-1 therapy at our institution between 2013 and 2016. All patients without adequate clinical or radiologic follow-up data in the electronic medical records were excluded. Imaging examinations for all patients deemed by their thoracic oncologists to have radiologic pseudoprogression or therapy-associated pneumonitis were reviewed by experienced thoracic radiologists. A total of 166 patients with NSCLC had available clinical and imaging data for retrospective review. Of these patients, 4 (2%) were considered to have radiologic pseudoprogression, 3 of which manifested as increased tumor size and 1 of which manifested with new lesions. A total of 5 patients (3%) were clinically deemed to have pneumonitis attributable to anti-PD-1 therapy, 4 of which had radiologic manifestations on computed tomography. Radiologic pseudoprogression and drug-induced pneumonitis are uncommon but important manifestations of anti-PD-1 therapy on thoracic imaging.

Hammer M ，Bagley S ，Aggarwal C ，Bauml J ，Nachiappan AC ，Simone CB 2nd ，Langer C ，Katz SI ... -  《-》

Patterns of response in metastatic NSCLC during PD-1 or PD-L1 inhibitor therapy: Comparison of the RECIST 1.1 and iRECIST criteria.

Immunotherapy plays an important role in advanced non-small cell lung cancer (NSCLC). However, radiological evaluation is challenging due to the potential inflammatory effects of immunotherapy, which can lead to atypical response patterns. Identifying these atypical responses is critical to making treatment decisions and prognostication. We performed a retrospective analysis of consecutive advanced NSCLC patients treated with immunotherapy (alone or in combination). We collected patients' clinical and pathological data, analyzed the proportion of patients who continued immunotherapy beyond progressive disease (PD) per RECIST 1.1, and compared the differences in response patterns between the RECIST 1.1 and iRECIST criteria. A total of 43 patients treated at the Peking Union Medical College, China from January 2018 to April 2019 were included. Continued immunotherapy beyond PD per RECIST 1.1 was observed in 10 (33.3%, 10/30) patients, of which there were discordant assessments (30%, 3/10) between the RECIST 1.1 and iRECIST, which were evaluated as PD by RECIST 1.1 and immune unconfirmed PD by iRECIST. Among seven patients with immune confirmed PD, one (1/30, 3.3%) had pseudoprogression. Patients who continued immunotherapy beyond PD (n = 10) experienced significantly prolonged overall survival (not reached vs. 8.1 months: hazard ratio, 2.8; 95% confidence interval: 2.7-13.6, P = 0.03) compared with patients who did not continue immunotherapy beyond PD (n = 20). RECIST 1.1 evaluation underestimated the benefit of immunotherapy. Further research is required to optimize iRECIST and establish some criteria for selecting patients who will benefit from continued immunotherapy beyond PD per RECIST 1.1.

Liang H ，Xu Y ，Chen M ，Zhong W ，Wang M ，Zhao J ... -  《-》

Pseudoprogression in Previously Treated Patients with Non-Small Cell Lung Cancer Who Received Nivolumab Monotherapy.

Nivolumab is effective in the treatment of previously treated patients with advanced NSCLC. However, its radiological evaluation is challenging because of atypical patterns of response such as pseudoprogression. We examined the characteristics and outcomes of previously treated patients with NSCLC who were treated with nivolumab and experienced development of pseudoprogression. We conducted a 15-center retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab monotherapy. For the patients who showed pseudoprogression, we defined progression-free survival 1 (PFS1) as the time to Response Evaluation Criteria in Solid Tumors-defined first progressive disease and progression-free survival 2 (PFS2) as the time to Response Evaluation Criteria in Solid Tumors-defined second progressive disease or death. Among the 542 patients included, 20% and 53% showed a typical response and progression, respectively. Of the 14 (3%) patients who showed pseudoprogression, most (n = 10) showed a response within 3 months of nivolumab treatment. The median PFS1 and PFS2 were 1.0 and 7.3 months, respectively. The median PFS2 was significantly shorter in the patients who showed pseudoprogression than the PFS of the patients with a typical response (p < 0.001). In contrast, patients showing pseudoprogression had significantly longer overall survival than did patients showing typical progression (p = 0.001). Pseudoprogression was uncommon, and the duration of response in patients who showed pseudoprogression was shorter than that in patients who showed a typical response. However, the survival benefit of pseudoprogression was markedly better than that of typical progression. Further research is required to elucidate the characteristics of and mechanisms underlying pseudoprogression.

Fujimoto D ，Yoshioka H ，Kataoka Y ，Morimoto T ，Hata T ，Kim YH ，Tomii K ，Ishida T ，Hirabayashi M ，Hara S ，Ishitoko M ，Fukuda Y ，Hwang MH ，Sakai N ，Fukui M ，Nakaji H ，Morita M ，Mio T ，Yasuda T ，Sugita T ，Hirai T ... -  《-》

Comparison of RECIST, iRECIST, and PERCIST for the Evaluation of Response to PD-1/PD-L1 Blockade Therapy in Patients With Non-Small Cell Lung Cancer.

Beer L ，Hochmair M ，Haug AR ，Schwabel B ，Kifjak D ，Wadsak W ，Fuereder T ，Fabikan H ，Fazekas A ，Schwab S ，Mayerhoefer ME ，Herold C ，Prosch H ... -  《-》