Imaging at the nexus: how state of the art imaging techniques can enhance our understanding of cancer and fibrosis.

Both cancer and fibrosis are diseases involving dysregulation of cell signaling pathways resulting in an altered cellular microenvironment which ultimately leads to progression of the condition. The two disease entities share common molecular pathophysiology and recent research has illuminated the how each promotes the other. Multiple imaging techniques have been developed to aid in the early and accurate diagnosis of each disease, and given the commonalities between the pathophysiology of the conditions, advances in imaging one disease have opened new avenues to study the other. Here, we detail the most up-to-date advances in imaging techniques for each disease and how they have crossed over to improve detection and monitoring of the other. We explore techniques in positron emission tomography (PET), magnetic resonance imaging (MRI), second generation harmonic Imaging (SGHI), ultrasound (US), radiomics, and artificial intelligence (AI). A new diagnostic imaging tool in PET/computed tomography (CT) is the use of radiolabeled fibroblast activation protein inhibitor (FAPI). SGHI uses high-frequency sound waves to penetrate deeper into the tissue, providing a more detailed view of the tumor microenvironment. Artificial intelligence with the aid of advanced deep learning (DL) algorithms has been highly effective in training computer systems to diagnose and classify neoplastic lesions in multiple organs. Ultimately, advancing imaging techniques in cancer and fibrosis can lead to significantly more timely and accurate diagnoses of both diseases resulting in better patient outcomes.

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.

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.