Integrating [18F]-Fluorodeoxyglucose Positron Emission Tomography with Computed Tomography with Radiation Therapy and Immunomodulation in Precision Therapy for Solid Tumors.

[18F]-FDG positron emission tomography with computed tomography (PET/CT) imaging is widely used to enhance the quality of care in patients diagnosed with cancer. Furthermore, it holds the potential to offer insight into the synergic effect of combining radiation therapy (RT) with immuno-oncological (IO) agents. This is achieved by evaluating treatment responses both at the RT and distant tumor sites, thereby encompassing the phenomenon known as the abscopal effect. In this context, PET/CT can play an important role in establishing timelines for RT/IO administration and monitoring responses, including novel patterns such as hyperprogression, oligoprogression, and pseudoprogression, as well as immune-related adverse events. In this commentary, we explore the incremental value of PET/CT to enhance the combination of RT with IO in precision therapy for solid tumors, by offering supplementary insights to recently released joint guidelines.

Advances in CAR T Cell Therapy for Non-Small Cell Lung Cancer.

Since its first approval by the FDA in 2017, tremendous progress has been made in chimeric antigen receptor (CAR) T cell therapy, the adoptive transfer of engineered, CAR-expressing T lymphocyte. CAR T cells are all composed of three main elements: an extracellular antigen-binding domain, an intracellular signaling domain responsible for T cell activation, and a hinge that joins these two domains. Continuous improvement has been made in CARs, now in their fifth generation, particularly in the intracellular signaling domain responsible for T cell activation. CAR T cell therapy has revolutionized the treatment of hematologic malignancies. Nonetheless, the use of CAR T cell therapy for solid tumors has not attained comparable levels of success. Here we review the challenges in achieving effective CAR T cell therapy in solid tumors, and emerging CAR T cells that have shown great promise for non-small cell lung cancer (NSCLC). A growing number of clinical trials have been conducted to study the effect of CAR T cell therapy on NSCLC, targeting different types of surface antigens. They include epidermal growth factor receptor (EGFR), mesothelin (MSLN), prostate stem cell antigen (PSCA), and mucin 1 (MUC1). Potential new targets such as erythropoietin-producing hepatocellular carcinoma A2 (EphA2), tissue factor (TF), and protein tyrosine kinase 7 (PTK7) are currently under investigation in clinical trials. The challenges in developing CAR T for NSCLC therapy and other approaches for enhancing CAR T efficacy are discussed. Finally, we provide our perspective on imaging CAR T cell action by reviewing the two main radionuclide-based CAR T cell imaging techniques, the direct labeling of CAR T cells or indirect labeling via a reporter gene.

Advances in PET/CT Imaging for Breast Cancer.

One out of eight women will be affected by breast cancer during her lifetime. Imaging plays a key role in breast cancer detection and management, providing physicians with information about tumor location, heterogeneity, and dissemination. In this review, we describe the latest advances in PET/CT imaging of breast cancer, including novel applications of 18F-FDG PET/CT and the development and testing of new agents for primary and metastatic breast tumor imaging and therapy. Ultimately, these radiopharmaceuticals may guide personalized approaches to optimize treatment based on the patient's specific tumor profile, and may become a new standard of care. In addition, they may enhance the assessment of treatment efficacy and lead to improved outcomes for patients with a breast cancer diagnosis.

Imaging the Side Effects of CAR T Cell Therapy: A Primer for the Practicing Radiologist.

Chimeric antigen receptor (CAR) T cell therapy is a revolutionary form of immunotherapy that has proven to be efficacious in the treatment of many hematologic cancers. CARs are modified T lymphocytes that express an artificial receptor specific to a tumor-associated antigen. These engineered cells are then reintroduced to upregulate the host immune responses and eradicate malignant cells. While the use of CAR T cell therapy is rapidly expanding, little is known about how common side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) present radiographically. Here we provide a comprehensive review of how side effects present in different organ systems and how they can be optimally imaged. Early and accurate recognition of the radiographic presentation of these side effects is critical to the practicing radiologist and their patients so that these side effects can be promptly identified and treated.

Novel Targets, Novel Treatments: The Changing Landscape of Non-Small Cell Lung Cancer.

Treatment of non-small cell lung cancer (NSCLC) has undergone a paradigm shift. Once a disease with limited potential therapies, treatment options for patients have exploded with the availability of molecular testing to direct management and targeted therapies to treat tumors with specific driver mutations. New in vitro diagnostics allow for the early and non-invasive detection of disease, and emerging in vivo imaging techniques allow for better detection and monitoring. The development of checkpoint inhibitor immunotherapy has arguably been the biggest advance in lung cancer treatment, given that the vast majority of NSCLC tumors can be treated with these therapies. Specific targeted therapies, including those against KRAS, EGFR, RTK, and others have also improved the outcomes for those individuals bearing an actionable mutation. New and emerging therapies, such as bispecific antibodies, CAR T cell therapy, and molecular targeted radiotherapy, offer promise to patients for whom none of the existing therapies have proved effective. In this review, we provide the most up-to-date survey to our knowledge regarding emerging diagnostic and therapeutic strategies for lung cancer to provide clinicians with a comprehensive reference of the options for treatment available now and those which are soon to come.

More than Just Skin-Deep: A Review of Imaging's Role in Guiding CAR T-Cell Therapy for Advanced Melanoma.

Advanced melanoma is one of the deadliest cancers, owing to its invasiveness and its propensity to develop resistance to therapy. Surgery remains the first-line treatment for early-stage tumors but is often not an option for advanced-stage melanoma. Chemotherapy carries a poor prognosis, and despite advances in targeted therapy, the cancer can develop resistance. CAR T-cell therapy has demonstrated great success against hematological cancers, and clinical trials are deploying it against advanced melanoma. Though melanoma remains a challenging disease to treat, radiology will play an increasing role in monitoring both the CAR T-cells and response to therapy. We review the current imaging techniques for advanced melanoma, as well as novel PET tracers and radiomics, in order to guide CAR T-cell therapy and manage potential adverse events.

Translating Molecules into Imaging-The Development of New PET Tracers for Patients with Melanoma.

Melanoma is a deadly disease that often exhibits relentless progression and can have both early and late metastases. Recent advances in immunotherapy and targeted therapy have dramatically increased patient survival for patients with melanoma. Similar advances in molecular targeted PET imaging can identify molecular pathways that promote disease progression and therefore offer physiological information. Thus, they can be used to assess prognosis, tumor heterogeneity, and identify instances of treatment failure. Numerous agents tested preclinically and clinically demonstrate promising results with high tumor-to-background ratios in both primary and metastatic melanoma tumors. Here, we detail the development and testing of multiple molecular targeted PET-imaging agents, including agents for general oncological imaging and those specifically for PET imaging of melanoma. Of the numerous radiopharmaceuticals evaluated for this purpose, several have made it to clinical trials and showed promising results. Ultimately, these agents may become the standard of care for melanoma imaging if they are able to demonstrate micrometastatic disease and thus provide more accurate information for staging. Furthermore, these agents provide a more accurate way to monitor response to therapy. Patients will be able to receive treatment based on tumor uptake characteristics and may be able to be treated earlier for lesions that with traditional imaging would be subclinical, overall leading to improved outcomes for patients.

Current and Future Role of Medical Imaging in Guiding the Management of Patients With Relapsed and Refractory Non-Hodgkin Lymphoma Treated With CAR T-Cell Therapy.

Chimeric antigen receptor (CAR) T-cells are a novel immunotherapy available for patients with refractory/relapsed non-Hodgkin lymphoma. In this indication, clinical trials have demonstrated that CAR T-cells achieve high rates of response, complete response, and long-term response (up to 80%, 60%, and 40%, respectively). Nonetheless, the majority of patients ultimately relapsed. This review provides an overview about the current and future role of medical imaging in guiding the management of non-Hodgkin lymphoma patients treated with CAR T-cells. It discusses the value of predictive and prognostic biomarkers to better stratify the risk of relapse, and provide a patient-tailored therapeutic strategy. At baseline, high tumor volume (assessed on CT-scan or on [18F]-FDG PET/CT) is a prognostic factor associated with treatment failure. Response assessment has not been studied extensively yet. Available data suggests that current response assessment developed on CT-scan or on [18F]-FDG PET/CT for cytotoxic systemic therapies remains relevant to estimate lymphoma response to CAR T-cell therapy. Nonetheless, atypical patterns of response and progression have been observed and should be further analyzed. The potential advantages as well as limitations of artificial intelligence and radiomics as tools providing high throughput quantitative imaging features is described.

Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death.

Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells. After ionizing radiation, oxaliplatin, or cisplatin treatment, fractions of treated cancer cell populations were eliminated through cell-autonomous death mechanisms, while other fractions of the treated cancer cells engulfed and killed neighboring cells through non-cell-autonomous processes, including cellular cannibalism. Under conditions of treatment with paclitaxel, non-cell-autonomous and cell-autonomous death were both detected in the treated cell population, while untreated neighboring cells exhibited features of apoptotic demise. The transcriptional activity of p53 tumor-suppressor protein contributed to the execution of cell-autonomous death, yet failed to affect the non-cell-autonomous death by cannibalism for the majority of tested anticancer agents, indicating that the induction of non-cell-autonomous death can occur under conditions in which cell-autonomous death was impaired. Altogether, these results reveal that chemotherapy and radiotherapy can induce both non-cell-autonomous and cell-autonomous death of cancer cells, highlighting the heterogeneity of cell death responses to anticancer treatments and the unsuspected potential contribution of non-cell-autonomous death to the global effects of anticancer treatment.

Entosis: The emerging face of non-cell-autonomous type IV programmed death.

The present review summarizes recent experimental evidences about the existence of the non-cell-autonomous death entosis in physiological and pathophysiological contexts, discusses some aspects of this form of cell death, including morphological, biochemical and signaling pathways that distinguish non-cell-autonomous demises from other death modalities and propose to define this new modality of death as type IV programmed cell death.

Diagnosing autism spectrum disorders in elderly people.

BACKGROUND: As autism spectrum disorders (ASD) have largely been neglected in old-age psychiatry, the objective of the present paper is to describe the diagnostic process in elderly patients. METHODS: A systematic review of the literature on ASD in older age was undertaken and illustrated by a case series of three elderly patients first diagnosed with ASD in later life by a tertiary mental health clinic. RESULTS: The search of the literature only yielded three papers on late-life ASD, while the review of the available diagnostic procedures among adults suggests some relevance for screening instruments (Autism Questionnaire), diagnostic instruments (Module 4, Autism Diagnostic Observation Schedule), and neuropsychological examination to profile impairments. Nonetheless, the case reports clearly showed that taking a thorough history with the patient, corroborated and supplemented by a close relative or caregiver who has known the patient for at least ten years, still remains the most important diagnostic tool. CONCLUSION: The three case studies show that in clinical practice ASD can easily be missed in elderly individuals presenting with comorbid psychiatric disorders, potentially causing iatrogenic damage. Although further research on phenotyping and diagnosing ASD in older people is warranted, the most important step at this point is to create a greater awareness of the possibility of ASD in old age among health-care professionals working with people in this age group.