Atypical Response Patterns Research Articles

Real-world response assessment of immune checkpoint inhibition: comparing iRECIST and RECIST 1.1 in melanoma and non-small cell lung cancer patients.

To compare immune response evaluation criteria in solid tumors (iRECIST) and response evaluation criteria in solid tumors (RECIST) 1.1 for response assessment of immune checkpoint inhibitor (ICI) therapy in a real-world setting in patients with melanoma and non-small cell lung cancer (NSCLC). Two-hundred fifty-two patients with melanoma and NSCLC who received CTLA-4 inhibitor ipilimumab or PD-1 inhibitors nivolumab or pembrolizumab and who underwent staging CT of the chest and abdomen were retrospectively included. Treatment response evaluation according to the RECIST 1.1 and iRECIST guidelines was performed for all patients. Response patterns, as well as overall response rate (ORR), disease control rate (DCR), and time to progression (TTP), were compared between RECIST 1.1 and iRECIST. Out of 143 patients with progressive disease (PD) according to RECIST 1.1, 48 (33.6%) did not attain confirmation of progression (iCPD) as per iRECIST and six patients who were treated beyond RECIST 1.1 progression reached PD at a later point in time in iRECIST, resulting in a significant difference in TTP between iRECIST and RECIST 1.1 (618.3 ± 626.9 days vs. 538.1 ± 617.9 days, respectively (p < 0.05)). The number of non-responders as per RECIST 1.1 was 79, whereas it was 60 when using iRECIST. ORR was 28.5% for RECIST 1.1 and 34.1% for iRECIST, and corresponding DCR of 67.4% for RECIST 1.1 and 74.6% for iRECIST. iRECIST was more suitable than RECIST 1.1 for capturing atypical response patterns to ICI therapy in patients with melanoma and NSCLC, resulting in differences in the assessment of treatment response. Compared to RECIST 1.1, iRECIST may improve patient care and treatment decisions for patients with NSCLC or melanoma who are treated with immune checkpoint inhibitors in clinical routine. RECIST 1.1 may incorrectly assess atypical treatment patterns to immune checkpoint inhibitors. iRECIST better captured atypical response patterns compared to RECIST 1.1. iRECIST was more suitable for assessing response to immune checkpoint inhibitors in non-small cell lung carcinoma and melanoma.

Advances in Imaging-Based Evaluation of Solid Tumors Treated With Immune Checkpoint Inhibitors

Immune checkpoint inhibitors have shown remarkable benefits in the treatment of solid tumors,while the occurrence of atypical response patterns and immune-related adverse events during treatment challenges the accuracy of therapeutic evaluation.Medical imaging is crucial for the evaluation of immunotherapy.It enables the assessment of treatment efficacy via both morphological and functional ways and offers unique a predictive value when being combined with artificial intelligence.Here we review the recent research progress in imaging-based evaluation of solid tumors treated with immune checkpoint inhibitors.

18F]FDG-PET/CT atypical response patterns to immunotherapy in non-small cell lung cancer patients: long term prognosis assessment and clinical management proposal.

To determine the long-term prognosis of immune-related response profiles (pseudoprogression and dissociated response), not covered by conventional PERCIST criteria, in patients with non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs). 109 patients were prospectively included and underwent [18F]FDG-PET/CT at baseline, after 7 weeks (PETinterim1), and 3 months (PETinterim2) of treatment. On PETinterim1, tumor response was assessed using standard PERCIST criteria. In the event of PERCIST progression at this time-point, the study design provided for continued immunotherapy for 6 more weeks. Additional response patterns were then considered on PETinterim2: pseudo-progression (PsPD, subsequent metabolic response); dissociated response (DR, coexistence of responding and non-responding lesions), and confirmed progressive metabolic disease (cPMD, subsequent homogeneous progression of lesions). Patients were followed up for at least 12 months. Median follow-up was 21 months. At PETinterim1, PERCIST progression was observed in 60% (66/109) of patients and ICPI was continued in 59/66. At the subsequent PETinterim2, 14% of patients showed PsPD, 11% DR, 35% cPMD, and 28% had a sustained metabolic response. Median overall survival (OS) and progression-free-survival (PFS) did not differ between PsPD and DR (27 vs 29 months, p = 1.0; 17 vs 12 months, p = 0.2, respectively). The OS and PFS of PsPD/DR patients were significantly better than those with cPMD (29 vs 9 months, p < 0.02; 16 vs 2 months, p < 0.001), but worse than those with sustained metabolic response (p < 0.001). This 3-group prognostic stratification enabled better identification of true progressors, outperforming the prognostic value of standard PERCIST criteria (p = 0.03). [18F]FDG-PET/CT enables early assessment of response to immunotherapy. The new wsPERCIST ("wait and see") PET criteria proposed, comprising immune-related atypical response patterns, can refine conventional prognostic stratification based on PERCIST criteria. HDH F20230309081206. Registered 20 April 2023. Retrospectively registered.

Total metabolic tumor volume on 18F-FDG PET/CT is a game-changer for patients with metastatic lung cancer treated with immunotherapy

PurposeBecause of atypical response imaging patterns in patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs), new biomarkers are needed for a better monitoring of...

Assessing Radiological Response to Immunotherapy in Lung Cancer: An Evolving Arena.

In the past decade, immune checkpoint inhibitors (ICIs) have entered the treatment landscape of non-small-cell lung cancer, signalling a paradigm shift within the field characterized by significant survival benefits for patients with advanced and metastatic disease, and especially those with non-targetable genetic oncogenic driver mutations. However, the shift towards immune-based treatments has created new challenges in oncology. Atypical immunotherapy response patterns, including pseudo-progression and hyperprogressive disease, as well as immune-related adverse events have generated the need for new methods to predict patient response to treatment. Hence, new versions of the traditional Response Evaluation Criteria for Solid Tumors (RECIST) have emerged to help characterise with better accuracy radiological findings concerning patient response classification to immunotherapy. This review discusses response evaluation criteria relevant to unique radiological findings observed in patients treated with immunotherapy for non-small-cell lung cancer.

Traumatic Brain Injury and Abnormal Moral Judgment

This article explains the underlying mechanism of utilitarian decisions in Traumatic Brain Injury (TBI) patients when pondering trolley-type moral dilemmas. In the first section of the literature review, definitions of TBI, utilitarianism and abnormal moral judgment have been provided. The ventromedial prefrontal cortex (vmPFC) has been identified to be undoubtedly prominent based on a discussion of the previous contradictory evidences about the brain areas involved in causing abnormal moral judgment. Subsequently, the function of vmPFC as an emotional integration station is introduced, substantiated by functional magnetic resonance imaging studies and the dual-system theory of moral decision-making. The inability or the diminished ability to feel morally-related emotions following TBI has also been considered a causal factor of endorsement to the act of harming someone directly. Finally, the author advises a few future directions to fill the gap within current knowledge and points out the limitations of thought experiments. Overall, the paper highlighted that the atypical response pattern of moral judgment in TBI patients is attributed to the failure to generate appropriate emotions in the face of moral stimuli.

Application of radiomics and artificial intelligence in lung cancer immunotherapy: a guide and hurdles from clinical trials

Immunotherapy has shown promising results with improved progression-free survival and overall survival in lung cancer. However, novel immunotherapy could generate atypical response patterns, which is a big challenge for traditional imaging criteria. Radiomics, combined with artificial intelligence (AI), represents new quantitative methodologies that could serve as an additional imaging biomarker to predict immunotherapy benefits and assess responses to assist oncologists in decision-making in lung cancer treatment. This paper aims to review the latest advancement of AI-based radiomics applied to lung cancer patients receiving immunotherapy, focusing on the fundamentals of these approaches and commonly used techniques. We also address the hurdles in the AI and radiomic analysis pipeline to guide clinicians in approaching this new concept.

Atypical response patterns in Chinese patients with cancer with immune checkpoint blockade.

e14631 Background: As specific patterns of progression, atypical responses, including pseudoprogression (PsPD) and dissociated response (DR), have been recently described. The purpose of the present study was to evaluate the frequency and prognosis of PsPD and DR in Chinese cancer patients treated with immune checkpoint inhibitors. Methods: We retrospectively reviewed patients with advanced cancer who received PD-1/PD-L1 inhibitor alone or combination therapy in a single center between December 2019 and January 2022. We evaluated all measurable lesions in each organ to identify PsPD and DR independently of RECIST 1.1. PsPD was defined as RECIST-defined progression followed by stabilization or decrease at the next imaging, and DR as concomitant decrease in some lesions and increase in others or emerging new lesions at a same timepoint. Progression‐free survival (PFS) and overall survival (OS) was compared between patients with atypical responses and those with true response (CR/PR) or nonresponse (SD/PD) using Cox proportional hazards models. Results: The present study included 178 patients aged 18-81 years (median: 63 years). The overall response rate was 18.5%. PsPD and DR were observed in 12 (6.7%) and 7 (3.9%) patients, respectively, and were not associated with any patient’s baseline characteristics. Median PFS (10.9 vs. 5.3 months; p=0.041) and OS (24.1 vs. 13.2 months; p=0.010) was significantly longer in patients with atypical response versus nonresponse, but shorter versus true responses (PFS: 10.9 vs. 35.4 months; p=0.009; OS: 24.1 vs. NR months; p=0.047). Patients with DR had a longer median PFS (10.1 vs. 1.5 months; p&lt;0.0001) and OS (23.9 vs. 5.6 months; p=0.0001) than those with true PD. All patients with PsPD or DR were administrated with continuing ICIs. Among patients who experienced an initial progression (excluding patients with PsPD and DR), the continuing ICIs treatment cohort (n=20) still had a significantly longer median OS (7.5 vs. 3.1 months; p=0.004) than discontinuing ICIs treatment cohort (n=11). Conclusions: PsPD and DR are uncommon patterns of disease progression. Patients with DR exhibited a relatively favorable clinical outcome. Prognosis or biomarkers are needed to identify early patients with atypical responses who will benefit from immunotherapy.

Individual patient-level data validation of surrogate and modified endpoints for immunotherapy in advanced hepatocellular carcinoma: Post-hoc analysis of IMbrave150 and real-world observations.

4090 Background: Immune checkpoint inhibitors (ICIs) have become the preferred treatment for advanced hepatocellular carcinoma (HCC). Surrogate endpoints including overall response rate (ORR) and progression-free survival (PFS) are preferred outcome measures in early-phase trials. However, ICIs can induce atypical patterns of response and progression, calling into question the validity of surrogate endpoints as predictive of overall survival (OS) benefit. We performed a post-hoc analysis of a large, randomized phase 3 clinical trial (IMbrave150) and cross-sectional analysis of a multi-institution real-world environment (RWE) to assess the OS surrogacy of ORR and PFS using Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), or immune-modified RECIST (imRECIST) in patients treated with ICIs. Methods: The IMbrave150 cohort in our analysis included 279 out of 336 patients treated with atezolizumab and bevacizumab in the intent-to-treat population. The RWE cohort included 328 patients with Child-Pugh A or B disease treated in the first or subsequent-line setting with anti-PD-1/L1 therapies. RECIST, mRECIST, and imRECIST ORR and PFS data for the IMbrave150 cohort was determined by investigators and central review, while RECIST ORR and PFS data for the RWE cohort was determined by treating providers or retrospective review. Results: In the IMbrave150 and RWE cohorts, Child-Pugh A patients treated in the first-line setting with CR/PR showed greater OS versus patients with SD/PD (IMbrave150: HR 0.16, 95% CI 0.10-0.26; RWE: HR 0.25, 95% CI 0.15-0.43). CR was associated with the greatest OS benefit, followed by PR, SD, and PD. Patients treated in the second-line setting or with Child-Pugh B disease showed that ORR was able to discriminate OS benefit but hazard ratios were closer to the null. In both cohorts, there was a positive rank correlation between RECIST PFS and OS (IMbrave150: Kendall's τ = 0.44, p &lt; 0.001); RWE: Kendall's τ = 0.52, p &lt; 0.001). However, only 31-46% of the variance in OS rankings was explained by PFS rankings. mRECIST PFS and imRECIST PFS showed a positive rank correlation with OS, with an explained variance of 30% and 38% for mRECIST and imRECIST, respectively. Conclusions: Our results suggest that RECIST ORR is a robust surrogate endpoint in HCC treated with ICIs. In contrast, the explained variance between RECIST PFS and OS in both the IMbrave and RWE cohorts was limited. This may reflect the impact of ICIs on response to subsequent therapies which may extend OS benefit. Although prior studies have proposed that modifications to RECIST may lead to more accurate surrogate markers, mRECIST and imRECIST ORR or PFS in HCC treated with ICIs were not associated with greater predictive performance compared to RECIST.

Advanced CT Imaging, Radiomics, and Artificial Intelligence to Evaluate Immune Checkpoint Inhibitors’ Effects on Metastatic Renal Cell Carcinoma

Advances in the knowledge of renal cell carcinoma (RCC)’s oncogenesis have led to the development of new therapeutic approaches, such as immune checkpoint inhibitors (ICIs), which have improved the clinical outcomes of metastatic RCC (mRCC) patients. Our literature search led to a series of studies that were divided into four subcategories: RECIST criteria, radiomics and artificial intelligence, atypical response patterns, and body composition. These studies provide novel and promising data aimed at improving patient management and clinical outcomes, further strengthening the concept of precision medicine. Radiomics and artificial intelligence allow us to obtain—in a non-invasive fashion—a multitude of data that cannot be detected with the naked eye, offering potential advantages that might help to predict the response to treatments and possibly improve patients’ outcomes through a personalized therapeutic approach. The purpose of this literature review is to describe the available evidence on the role of computed tomography (CT) in evaluating and predicting ICIs’ effects on mRCC patients by applying radiomics and artificial intelligence.

Management of Non-Melanoma Skin Cancer: Radiologists Challenging and Risk Assessment.

Basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma are the three main types of nonmelanoma skin cancers and their rates of occurrence and mortality have been steadily rising over the past few decades. For radiologists, it is still difficult to treat patients with advanced nonmelanoma skin cancer. Nonmelanoma skin cancer patients would benefit greatly from an improved diagnostic imaging-based risk stratification and staging method that takes into account patient characteristics. The risk is especially elevated among those who previously received systemic treatment or phototherapy. Systemic treatments, including biologic therapies and methotrexate (MTX), are effective in managing immune-mediated diseases; however, they may increase susceptibility to NMSC due to immunosuppression or other factors. Risk stratification and staging tools are crucial in treatment planning and prognostic evaluation. PET/CT appears more sensitive and superior to CT and MRI for nodal and distant metastasis as well as in surveillance after surgery. The patient treatment response improved with advent and utilization of immunotherapy and different immune-specific criteria are established to standardized evaluation criteria of clinical trials but none of them have been utilized routinely with immunotherapy. The advent of immunotherapy has also arisen new critical issues for radiologists, such as atypical response pattern, pseudo-progression, as well as immune-related adverse events that require early identification to optimize and improve patient prognosis and management. It is important for radiologists to have knowledge of the radiologic features site of the tumor, clinical stage, histological subtype, and any high-risk features to assess immunotherapy treatment response and immune-related adverse events.

Novelties from the Joint EANM/SNMMI/ANZSNM Guidelines on Immunotherapy.

In the past decade, the implementation of immunotherapy with checkpoint inhibitors has determined a major change in the management of oncological patients. The challenges associated to the new therapeutic regimen have promoted adapted criteria for response assessment to interpret imaging findings and atypical patterns of response. Parallel to the new morphological criteria, also 18fluoro-deoxyglucose positron emission/computed tomography imaging has required novel approaches and specific guidelines on how to perform, interpret, and report the scan in patients with solid tumors under immune checkpoint inhibitors therapy. A summary of the novelties related to the new joint international European Association of Nuclear Medicine (EANM)/Society of Nuclear Medicine and Molecular Imaging (SNMMI)/Australian and New Zealand Society of Nuclear Medicine (ANZSNM) guidelines on immunotherapy is provided herein to elucidate most critical aspects in image interpretation.

Imaging of Immune Checkpoint Inhibitor Immunotherapy for Non-Small Cell Lung Cancer.

The normal immune system identifies and eliminates precancerous and cancerous cells. However, tumors can develop immune resistance mechanisms, one of which involves the exploitation of pathways, termed immune checkpoints, that normally suppress T-cell function. The goal of immune checkpoint inhibitor (ICI) immunotherapy is to boost T-cell-mediated immunity to mount a more effective attack on cancer cells. ICIs have changed the treatment landscape of advanced non-small cell lung cancer (NSCLC), and numerous ICIs have now been approved as first-line treatments for NSCLC by the U.S. Food and Drug Administration. ICIs can cause atypical response patterns such as pseudoprogression, whereby the tumor burden initially increases but then decreases. Therefore, response criteria have been developed specifically for patients receiving immunotherapy. Because ICIs activate the immune system, they can lead to inflammatory side effects, termed immune-related adverse events (irAEs). Usually occurring within weeks to months after the start of therapy, irAEs range from asymptomatic abnormal laboratory results to life-threatening conditions such as encephalitis, pneumonitis, myocarditis, hepatitis, and colitis. It is important to be aware of the imaging appearances of the various irAEs to avoid misinterpreting them as metastatic disease, progressive disease, or infection. The basic principles of ICI therapy; indications for ICI therapy in the setting of NSCLC; response assessment and atypical response patterns of ICI therapy, as compared with conventional chemotherapy; and the spectrum of irAEs seen at imaging are reviewed. An invited commentary by Nishino is available online. ©RSNA, 2022.

Management of cutaneous melanoma: radiologists challenging and risk assessment.

Melanoma patient remains a challenging for the radiologist, due to the difficulty related to the management of a patient more often in an advanced stage of the disease. It is necessary to determine a stratification of risk, optimizing the means, with diagnostic tools that should be optimized in relation to the type of patient, and improving knowledge. Staging and risk assessment procedures are determined by disease presentation at diagnosis. Melanoma staging is a critical tool to assist clinical decision-making and prognostic assessment. It is used for clinical trial design, eligibility, stratification, and analysis. The current standard for regional lymph nodes staging is represented by the sentinel lymph node excision biopsy procedure. For staging of distant metastases, PET-CT has the highest sensitivity and diagnostic odds ratio. Similar trend is observed during melanoma surveillance. The advent of immunotherapy, which has improved patient outcome, however, has determined new issues for radiologists, partly due to atypical response patterns, partly due to adverse reactions that must be identified as soon as possible for the correct management of the patient. The main objectives of the new ir-criteria are to standardize the assessment between different trials. However, these ir-criteria do not take into account all cases of atypical response patterns, as hyperprogression or dissociated responses. None of these criteria has actually been uniformly adopted in routine. The immune-related adverse events (irAEs) can involve various organs from head to toe. It is crucial for radiologists to know the imaging appearances of this condition, to exclude recurrent or progressive disease and for pneumonitis, since it could be potentially life-threatening toxicity, resulting in pneumonitis-related deaths in early phase trials, to allow a proper patient management.

The Impaired Subcortical Pathway From Superior Colliculus to the Amygdala in Boys With Autism Spectrum Disorder.

ObjectiveIncreasing evidence suggests that a subcortical pathway from the superior colliculus (SC) through the pulvinar to the amygdala plays a crucial role in mediating non-conscious processing in response to emotional visual stimuli. Given the atypical eye gaze and response patterns to visual affective stimuli in autism, we examined the functional and white matter structural difference of the pathway in boys with autism spectrum disorder (ASD) and typically developing (TD) boys.MethodsA total of 38 boys with ASD and 38 TD boys were included. We reconstructed the SC-pulvinar-amygdala pathway in boys with ASD and TD using tractography and analyzed tract-specific measurements to compare the white matter difference between the two groups. A region of interest-based functional analysis was also applied among the key nodes of the pathway to explore the functional connectivity network.ResultsDiffusion tensor imaging analysis showed decreased fractional anisotropy (FA) in pathways for boys with ASD compared to TD. The FA change was significantly associated with the atypical communication pattern in boys with ASD. In addition, compared to TD, we found that the ASD group was associated with increased functional connectivity between the right pulvinar and the left SC.ConclusionOur results indicated that the functional and white matter microstructure of the subcortical route to the amygdala might be altered in individuals with autism. This atypical structural change of the SC-pulvinar-amygdala pathway may be related to the abnormal communication patterns in boys with ASD.

Imaging of Cancer Immunotherapy: Response Assessment Methods, Atypical Response Patterns, and Immune-Related Adverse Events, From the AJR Special Series on Imaging of Inflammation.

The introduction of immunotherapy with immune-checkpoint inhibitors (ICIs) has revolutionized cancer treatment paradigms. Since FDA approval of the first ICI in 2011, multiple additional ICIs have been approved and granted marketing authorization, and many promising agents are in early clinical adoption. Due to the distinctive biologic mechanisms of ICIs, the patterns of tumor response and progression seen with immunotherapy differ from those observed with cytotoxic chemothera-pies. With increasing clinical adoption of immunotherapy, it is critical for radiologists to recognize different response patterns and common pitfalls to avoid misinterpretation of imaging studies or prompt premature cessation of potentially effective treatment. This review provides an overview of ICIs and their mechanisms of action and discusses anatomic and metabolic immune-related response assessment methods, typical and atypical patterns of immunotherapy response (including pseudoprogression, hyperprogression, dissociated response, and durable response), and common imaging features of immune-related adverse events. Future multicenter trials are needed to validate the proposed immune-related response criteria and identify the functional imaging markers of early treatment response and survival.

Cognitive flexibility in 12-month-old preterm and term infants is associated with neurobehavioural development in 18-month-olds

There is growing evidence that preterm children are at an increased risk of poor executive functioning, which underlies behavioural and attention problems. Previous studies have suggested that early cognitive flexibility is a possible predictor of later executive function; however, how it develops in infancy and relates to the later neurobehavioural outcomes is still unclear in the preterm population. Here, we conducted a longitudinal study to investigate oculomotor response shifting in 27 preterm and 25 term infants at 12 months and its relationship with general cognitive development and effortful control, which is a temperamental aspect closely associated with executive function, at 18 months. We found that moderate to late preterm and term infants significantly inhibited previously rewarded look responses, while very preterm infants did not show significant inhibition of perseverative looking at 12 months. Moreover, lower inhibition of perseverative looking was significantly associated with lower general cognitive development and attentional shifting at 18 months. These findings suggest that the early atypical patterns of oculomotor response shifting may be a behavioural marker for predicting a higher risk of negative neurobehavioural outcomes, including attention-related problems in preterm children.

Immune-related dissociated response as a specific atypical response pattern in solid tumors with immune checkpoint blockade.

Immune checkpoint blockade using immune checkpoint inhibitors, including cytotoxic T-lymphocyte-associated antigen–4 and programmed cell death protein-1/programmed cell death ligand–1 inhibitors, has revolutionized systematic treatment for advanced solid tumors, with unprecedented survival benefit and tolerable toxicity. Nivolumab, pembrolizumab, cemiplimab, avelumab, durvalumab, atezolizumab, and ipilimumab are currently approved standard treatment options for various human cancer types. The response rate to immune checkpoint inhibitors, however, is unsatisfactory, and unexpectedly, atypical radiological responses, including delayed responses, pseudoprogression, hyperprogression, and dissociated responses (DRs), are observed in a small subgroup of patients. The benefit of immunotherapy for advanced patients who exhibit atypical responses is underestimated according to the conventional response evaluation criteria in solid tumors (RECIST). In particular, DR is considered a mixed radiological or heterogeneous response pattern when responding and nonresponding lesions or new lesions coexist simultaneously. The rate of DR reported in different studies encompass a wide range of 3.3–47.8% based on diverse definition of DR. Although DR is also associated with treatment efficacy and a favorable prognosis, it is different from pseudoprogression, which has concordant progressive lesions and can be regularly captured by immune RECIST. This review article aims to comprehensively determine the frequency, definition, radiological evaluation, probable molecular mechanisms, prognosis, and clinical management of immune-related DR and help clinicians and radiologists objectively and correctly interpret this specific atypical response and better understand and manage cancer patients with immunotherapy and guarantee their best clinical benefit.

CAR T-Cell Therapy: An Update for Radiologists.

Chimeric antigen receptor-engineered (CAR) T-cell therapy is a promising novel immunotherapy that has the potential to revolutionize cancer treatment. Four CAR T-cell therapies have received FDA approval within the last 5 years, and the role of CAR T cells is anticipated to continue to evolve and expand. However, various aspects of CAR T-cell therapies remain poorly understood, and the therapies are associated with severe side effects, including cytokine release syndrome and immune effector cell-associated neurotoxicity, which require prompt diagnosis and intervention. The purposes of this review are to describe the role of imaging in diagnosing and monitoring toxicities from CAR T-cell therapies and explore the use of various imaging techniques, including PET/CT with novel radiotracers, to predict and assess treatment response and adverse effects. It is important for radiologists to recognize the imaging findings associated with each syndrome and to recognize the typical and atypical treatment response patterns associated with CAR T-cell therapy. Given the expected increase in use of CAR T cells in the near future, radiologists should familiarize themselves with the imaging findings encountered in these novel therapies so that they can provide comprehensive and up-to-date guidance for clinical management.

Dissociated Responses in Patients with Metastatic Solid Tumors Treated with Immunotherapy.

BackgroundImmune checkpoint inhibitors have been demonstrated to improve overall survival. Atypical patterns of response have been reported, including dissociated response (DR). We evaluated the prevalence of DR.Patients and methodsPatients had to have a baseline computed tomography (CT) scan and at least one follow-up CT scan and two target lesions (TLs). Three types of DR were evaluated using RECIST1.1: DR1, defined as at least one progressive and one responding TL; DR2, defined as at least one progressive and one stable TL; and DR3, defined as at least one stable and one responding TL.ResultsA total of 1244 measurements of 272 TLs were performed in 100 patients. Forty-nine out of the 272 TLs (18%) had received old or recent radiotherapy, and 42 (15%) had been biopsied. An objective response was observed in 22 patients (22%) and on 52 TLs (19%). DR1 were observed in 8% of patients. At the tumor measurement level, the response rate was lower in the case of prior radiotherapy (29% vs 34%, p = 0.01) and higher in the case of prior biopsy (40% vs 32%, p = 0.02).ConclusionsA DR was observed in 8% of patients. Response rate was lower in the case of prior radiotherapy and higher in the case of prior biopsy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40268-021-00362-3.