Evolution of Radiological Treatment Response Assessments for Cancer Immunotherapy: From iRECIST to Radiomics and Artificial Intelligence.

Immunotherapy has revolutionized and opened a new paradigm for cancer treatment. In the era of immunotherapy and molecular targeted therapy, precision medicine has gained emphasis, and an early response assessment is a key element of this approach. Treatment response assessment for immunotherapy is challenging for radiologists because of the rapid development of immunotherapeutic agents, from immune checkpoint inhibitors to chimeric antigen receptor-T cells, with which many radiologists may not be familiar, and the atypical responses to therapy, such as pseudoprogression and hyperprogression. Therefore, new response assessment methods such as immune response assessment, functional/molecular imaging biomarkers, and artificial intelligence (including radiomics and machine learning approaches) have been developed and investigated. Radiologists should be aware of recent trends in immunotherapy development and new response assessment methods.

Definition, Incidence, and Challenges for Assessment of Hyperprogressive Disease During Cancer Treatment With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

Importance: Hyperprogressive disease (HPD) is a recognized pattern of rapid tumor progression during immune checkpoint inhibitor (ICI) treatment. Definitions of HPD have not been standardized, posing the risk of capturing different tumoral behaviors. Objectives: To provide a systematic summary of definitions and the incidence of HPD in patients undergoing ICI treatment and discuss the challenges of current assessment of HPD. Data Sources: Articles that evaluated HPD published before March 3, 2020, were identified from MEDLINE and EMBASE. Study Selection: Clinical trials and observational studies providing the incidence and definition of HPD from patients with cancer treated with ICIs. Data Extraction and Synthesis: Factors included in the analysis comprised authors, year of publication, cancer type, ICI type, number of previous treatment lines, definition of HPD, time frame used to assess HPD, number of patients with HPD, onset of HPD, and prognosis of patients with HPD. Quantitative and qualitative syntheses for the incidence of HPD were performed. Main Outcomes and Measures: Definitions of HPD were categorized and the range of incidence of HPD was evaluated. Subgroup analysis on the incidence of HPD according to the category was performed and the challenges associated with current HPD assessment were evaluated. Results: Twenty-four studies with 3109 patients were analyzed. The incidence of HPD varied from 5.9% to 43.1%. The definitions were divided into 4 categories based on the calculation of tumor growth acceleration: tumor growth rate ratio (pooled incidence of HPD, 9.4%; 95% CI, 6.9%-12.0%), tumor growth kinetics ratio (pooled incidence, 15.8%; 95% CI, 8.0%-23.7%), early tumor burden increase (pooled incidence, 20.6%; 95% CI, 9.3%-31.8%), and combinations of the above (pooled incidence, 12.4%; 95% CI, 7.3%-17.5%). Hyperprogressive disease could be overestimated or underestimated if the assessment was limited to tumor growth rate or tumor growth kinetics ratio, target lesions, or response evaluation criteria in solid tumors (RECIST)-defined progressors, or if the assessment time frame conformed to RECIST. Study results on clinical outcome were heterogeneous on discriminating patients with HPD from those with natural progressive disease. Conclusions and Relevance: Definitions of HPD appear to be diverse, with the incidence of HPD varying from 5.9% to 43.1% across studies examined in this meta-analysis. Varying incidence and definitions of HPD indicate the need for establishing its uniform and clinically relevant criteria based on currently available evidence.

Impact of pseudoprogression and treatment beyond progression on outcome in patients with non-small cell lung cancer treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICI) have become an important treatment option for non-small cell lung cancer (NSCLC). We aimed to evaluate the clinical impact of pseudoprogression (PsP) and treatment beyond RECIST1.1-defined progressive disease (TBP) on outcome in NSCLC patients treated with ICI. Methods: NSCLC patients treated with ICI between Mar 2016 and July 2018 were recruited in a consecutive manner. Response was assessed every 8-12 weeks using RECIST1.1 and iRECIST. Based on iRECIST, PsP was defined as progressive disease (PD) on RECIST1.1 subsequently reset to non-PD categories. Using log-rank test, progression-free survival (PFS) was compared between patients with and without PsP, and overall survival (OS) was compared between patients treated with and without TBP. The impact of TBP on OS was evaluated through multivariate Cox proportional hazard models. Results: Of the 189 patients, seven (3.7%) experienced PsP which mostly occurred approximately 3 months after baseline. The median PFS was significantly longer in patients with PsP (not reached) than those without PsP (3.8 months, P = .02). Among patients who demonstrated PD according to RECIST1.1, median OS was significantly longer in patients with TBP (17.2 months) than those without TBP (7.4 months, P < .001). On multivariate analysis adjusting other covariates, TBP (HR, 0.4; 95% CI, 0.2-0.7) remained as a significant protective factor for mortality. Conclusion: PsP occurred in 3.7% of NSCLC patients under ICI treatment. Based on iRECIST scheme, PsP and TBP may be associated with survival benefit.

Pregnancy and neonatal outcomes of women with disabilities: a nationwide population-based study in South Korea.

We investigated (1) pregnancy and neonatal outcomes in women with and without disabilities, (2) time trends in deliveries, and (3) risks of pregnancy and neonatal complications among women with various disability types and severity. This was a nationwide population-based study merging the database of the Korea National Health Insurance claims, National Health Screening Program for Infants and Children, and Disability Registration System to compare perinatal outcomes in women with and without disabilities. Pregnancy and neonatal outcomes were analyzed during 2007 and 2015, as were time trends of deliveries. Multivariate logistic regression was used to evaluate risk of perinatal outcomes among women with various disability types and severities. Women with disabilities showed higher rates of cesarean section (aOR, 1.73; 95% CI, 1.69-1.77), hypertensive disorders (aOR, 1.74; 95% CI, 1.63-1.86), placenta abruption (aOR, 1.27; 95% CI, 1.12-1.45), placenta previa (aOR, 1.14; 95% CI, 1.05-1.24), stillbirths (aOR, 1.30; 95% CI, 1.17-1.45), preterm births (aOR, 1.67; 95% CI, 1.57-1.78), and LBW (aOR, 1.87; 95% CI, 1.78-1.97) than those without disabilities. From 2007 to 2015, although delivery rate in women with disabilities decreased steeply compared with that in women without disabilities, the rate of cesarean section increased in women with disabilities. Women with intellectual disability and those with vision impairment had the highest number of perinatal complications among women with various types of disabilities. Women with disability had more adverse pregnancy and neonatal outcomes than those without disabilities. Specific disability types & severities are more vulnerable to specific perinatal complications.

Reliable and robust method for abdominal muscle mass quantification using CT/MRI: An explorative study in healthy subjects.

BACKGROUND: Quantification of abdominal muscle mass by cross-sectional imaging has been increasingly used to diagnose sarcopenia; however, the technical method for quantification has not been standardized yet. We aimed to determine an optimal method to measure the abdominal muscle area. METHODS: Among 50 consecutive subjects who underwent abdominal CT and MRI for possible liver donation, total abdominal muscle area (TAMA) and total psoas muscle area (TPA) at the L3 inferior endplate level were measured by two blinded readers. Inter-scan agreement between CT and MRI and inter-reader agreement between the two readers were evaluated using intraclass correlation coefficient (ICC) and within-subject coefficient of variation (WSCV). To evaluate the effect of measurement level, one reader measured TAMA and TPA at six levels from the L2 to L4 vertebral bodies. RESULTS: TAMA was a more reliable biomarker than TPA in terms of inter-scan agreement (ICC: 0.928 vs. 0.788 for reader 1 and 0.853 vs. 0.821 for reader 2, respectively; WSCV: 8.3% vs. 23.4% for reader 1 and 10.4% vs. 22.3% for reader 2, respectively) and inter-reader agreement (ICC: 0.986 vs. 0.886 for CT and 0.865 vs. 0.669 for MRI, respectively; WSCV: 8.2% vs. 16.0% for CT and 11.6% vs. 29.7% for MRI, respectively). In terms of the measurement level, TAMA did not differ from the L2inf to L4inf levels, whereas TPA increased with a decrease in measurement level. CONCLUSIONS: TAMA is a better biomarker than TPA in terms of inter-scan and inter-reader agreement and robustness to the measurement level. CT was a more reliable imaging modality than MRI. Our results support the use of TAMA measured by CT as a standard biomarker for abdominal muscle area measurement.