Biological Bases of Immune-Related Adverse Events and Potential Crosslinks With Immunogenic Effects of Radiation

Immune checkpoint inhibitors have gained an established role in the treatment of different tumors. Indeed, their use has dramatically changed the landscape of cancer care, especially for tumor types traditionally known to have poor outcomes. However, stimulating anticancer immune responses may also elicit an unusual pattern of immune-related adverse events (irAEs), different from those of conventional chemotherapy, likely due to a self-tolerance impairment featuring the production of autoreactive lymphocytes and autoantibodies, or a non-specific autoinflammatory reaction. Ionizing radiation has proven to promote both positive pro-inflammatory and immunostimolatory activities, and negative anti-inflammatory and immunosuppressive mechanisms, as a result of cross-linked interactions among radiation dose, the tumor microenvironment and the host genetic predisposition. Several publications argue in favor of combining immunotherapy and a broad range of radiation schedules, based on the recent evidence of superior treatment responses and patient survival. The synergistic modulation of the immune response by radiation therapy and immunotherapeutics, particularly those manipulating T-cell activation, may also affect the type and severity of irAEs, suggesting a relationship between the positive antitumor and adverse autoimmune effects of these agents. As yet, information on factors that may help to predict immune toxicity is still lacking. The aim of our work is to provide an overview of the biological mechanisms underlying irAEs and possible crosslinks with radiation-induced anticancer immune responses. We believe such an overview may support the optimization of immunotherapy and radiotherapy as essential components of multimodal anticancer therapeutic approaches. Challenges in translating these to clinical practice are discussed

Synergism Between Immunotherapy and Radiotherapy in Esophageal Cancer: An Overview of Current Knowledge and Future Perspectives

Background: Esophageal cancer (EC) is an aggressive neoplasm of the gastrointestinal tract that is usually treated with a combination of chemotherapy, radiotherapy (RT), and/or surgery, according to disease status. Despite the availability of multimodal therapeutic strategies, local recurrence is frequently observed. Immunotherapy is a promising therapeutic approach that is currently highly investigated in association to standard therapies, including RT, with the aim to improve patients' outcomes. Materials and Methods: A PubMed search was performed with the following keywords in all fields: "esophageal cancer" and "radiotherapy" and "radiation" and "immunotherapy" and "PD-1" and "PD L1." For an overview of ongoing trials, an additional search on ClinicalTrials.gov website was performed using the keywords "esophageal cancer" and "immunotherapy" and "PD-L1" and "CTLA-4" and "radiation" and "radiotherapy." Emerging data from preclinical and clinical studies are suggesting a synergistic effect between immunotherapy and RT. With the aim to update the knowledge of this synergistic immune-mediated antitumor activity and discuss current challenges, the authors summarize published data concerning the basic mechanisms and the effectiveness and tolerance of the combination between immunotherapy and RT for patients with EC, followed by an overview of ongoing clinical trial. Conclusions: Published results encourage the use of personalized therapeutic approaches for EC patients in the future; results from ongoing studies will help to identify the optimal strategies for patient selection and treatment response evaluation

Diagnostic Value of Choline PET in the Preoperative Localization of Hyperfunctioning Parathyroid Gland(s): A Comprehensive Overview

Hyperparathyroidism is a metabolic disorder characterized by the excessive production of the parathyroid hormone. The diagnosis is based on clinical and laboratory data. In most cases the only treatment is surgery and a correct preoperatory localization of the hyperfunctioning parathyroid gland(s) is essential. Currently, ultrasonography combined with [Tc-99m]Tc-MIBI parathyroid scintigraphy, optionally associated with single photon emission computed tomography/computed tomography (SPECT/CT), represent the standard preoperative imaging. In recent years, a number of studies have evaluated the potential role of choline positron emission tomography (PET) in hyperparathyroidism with promising results. Most of the recent evidence underlined its higher sensitivity and diagnostic accuracy in the localization of hyperfunctioning parathyroid glands. Choline PET has a higher spatial resolution that is useful for the detection of smaller parathyroid glands and it also has shorter examination times and favorable radiation exposure. These are just a few of the aspects that support it to overcome traditional imaging. Moreover, from the preliminary data, the choline uptake mechanism seems to also have an impact on its better performance. For these reasons, if first used as second level imaging in patients with negative or inconclusive traditional imaging results, several authors have supported its use as a first line investigation. This comprehensive overview aims to provide an accurate description of the preliminary results available in the literature about the use of choline PET/CT in hyperparathyroidism and to compare these results with the performance of traditional imaging methods

18F-Fluorocholine PET/CT, Tc-99m-MIBI and TC-99m-MDP SPECT/CT in Tertiary Hyperparathyroidism with Renal Osteodystrophy

Tertiary hyperparathyroidism (HPT) is a metabolic disorder characterized by the semi-autonomous hypersecretion of parathyroid hormone (PTH), leading to hypercalcemia. It can be the end result of persistent secondary hyperparathyroidism and is most commonly observed in patients with long-standing chronic kidney disease (CKD) and often after renal transplantation. Untreated HPT can lead to progressive bone disease, fibrocystic osteitis, and soft-tissue calcifications, along with other severe complications. In the 2009 Kidney Disease Improving Global Outcomes (KDIGO) guidelines, CKD-Mineral and Bone Disorder (CKD-MBD) is used to describe the broader clinical syndrome encompassing mineral, bone, and calcific cardiovascular abnormalities that develop as a complication of CKD. We report a 62-year-old female with a severe HPT evolved from advanced chronic kidney disease (stage 5D, KDIGO). Patient was evaluated with multimodality nuclear medicine functional imaging to assess hyperfunctioning parathyroid glands and bone lesions. Tc-99m-methoxyisobutylisonitrile (MIBI) dual-phase scintigraphy, Tc-99m-methylenediphosphonate (MDP) bone scan and 18F-Fluorocholine positron emission tomography/computed tomography ( 18F-FCH PET/CT) were performed before surgery

Comparison of the Diagnostic Value of MRI and Whole Body 18F-FDG PET/CT in Diagnosis of Spondylodiscitis

Spondylodiscitis is a spine infection for which a diagnosis by a magnetic resonance imaging (MRI) is considered the most appropriate imaging technique. The aim of this study was to compare the role of an F-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) and an MRI in this field. For 56 patients with suspected spondylodiscitis for whom MRI and F-18-FDG PET/CT were performed, we retrospectively analyzed the results. Cohen's kappa was applied to evaluate the agreement between the two techniques in all patients and in subgroups with a different number of spinal districts analyzed by the MRI. Sensitivity, specificity, and accuracy were also evaluated. The agreements of the F-18-FDG PET/CT and MRI in the evaluation of the entire population, whole-spine MRI, and two-districts MRI were moderate (kappa = 0.456, kappa = 0.432, and kappa = 0.429, respectively). In patients for whom one-district MRI was performed, F-18-FDG PET/CT and MRI were both positive and completely concordant (kappa = 1). We also separately evaluated patients with suspected spondylodiscitis caused by Mycobacterium tuberculosis for whom the MRI and F-18-FDG PET/CT were always concordant excepting in 2 of the 18 (11%) patients. Sensitivity, specificity, and accuracy of the MRI and F-18-FDG PET/CT were 100%, 60%, 97%, and 92%, 100%, and 94%, respectively. Our results confirmed the F-18-FDG PET/CT diagnostic value in the diagnosis of spondylodiscitis is comparable to that of MRI for the entire spine evaluation. This could be considered a complementary technique or a valid alternative to MRI

Safety culture to improve accidental events reporting in radiotherapy

The potential for unintended and adverse radiation exposure in radiotherapy is real and should be studied because radiotherapy is a highly complex, multistep process which requires input from numerous individuals from different areas and steps of the radiotherapy workflow. The 'Incident' (I) is a consequence of which are not negligible from the point of view of protection or safety. A 'near miss' (NM) is defined as an event which is highly likely to happen but did not occur. The purpose of this work is to show that through a systematic reporting and analysis of these adverse events, their occurrence can be reduced

Adding Concomitant Chemotherapy to Postoperative Radiotherapy in Oral Cavity Carcinoma with Minor Risk Factors: Systematic Review of the Literature and Meta-Analysis

Simple Summary Oral cavity carcinoma (OCC) is the 11th most frequently diagnosed cancer; despite a multimodal treatment, locally advanced OCC, managed by surgery and adjuvant therapies, remains at high risk of recurrence, with a 5-year overall survival (OS) of 51%. The efficacy of postoperative chemotherapy in addition to radiotherapy (POCRT) in low-intermediate risk OCC is a controversial matter in the absence of high-risk features (ENE, R1). To establish the role of POCRT in a population with solely minor risk factors (perineural invasion or lymph vascular invasion; pN1 single; DOI >= 5 mm; close margin; node-positive level IV or V; pT3 or pT4; multiple lymph nodes without ENE), we performed a systematic review and meta-analyses focused on OS, disease-free survival (DFS), and local-recurrence-free survival (LRFS). Thirteen studies met the inclusion criteria and were included in the quantitative meta-analyses. Our preliminary results are in favor of POCRT in terms of OS but not conclusive for DFS and LRFS. Further analyses are suggested. When presenting with major pathological risk factors, adjuvant radio-chemotherapy for oral cavity cancers (OCC) is recommended, but the addition of chemotherapy to radiotherapy (POCRT) when only minor pathological risk factors are present is controversial. A systematic review following the PICO-PRISMA methodology (PROSPERO registration ID: CRD42021267498) was conducted using the PubMed, Embase, and Cochrane libraries. Studies assessing outcomes of POCRT in patients with solely minor risk factors (perineural invasion or lymph vascular invasion; pN1 single; DOI >= 5 mm; close margin < 2-5 mm; node-positive level IV or V; pT3 or pT4; multiple lymph nodes without ENE) were evaluated. A meta-analysis technique with a single-arm study was performed. Radiotherapy was combined with chemotherapy in all studies. One study only included patients treated with POCRT. In the other 12 studies, patients were treated with only PORT (12,883 patients) and with POCRT (10,663 patients). Among the patients treated with POCRT, the pooled 3 year OS rate was 72.9% (95%CI: 65.5-79.2%); the pooled 3 year DFS was 70.9% (95%CI: 48.8-86.2%); and the pooled LRFS was 69.8% (95%CI: 46.1-86.1%). Results are in favor of POCRT in terms of OS but not significant for DFS and LRFS, probably due to the heterogeneity of the included studies and a combination of different prognostic factors

Diagnostic Value of the Early Heart-to-Mediastinum Count Ratio in Cardiac 123I-mIBG imaging for Parkinson's Disease

Early diagnosis of Parkinson's disease (PD) is of primary importance. The delayed (3-4 h after injection) Iodine-123-Metaiodobenzylguanidine (123I-mIBG) scintigraphy has been proven to be effective in early differential diagnosis for Lewy body disease. But early imaging (15-30 min after injection) has only been marginally studied for its possible diagnostic role. In this prospective study a thresholdfor the early Heart-to-Mediastinum (H/M) count ratio has been investigated, obtaining a diagnostic accuracy analogous to conventional, delayed imaging

CT pulmonary angiography appropriateness in a single emergency department: does the use of revised Geneva score matter?

Purpose: To assess the percentage of computed tomography pulmonary angiography (CTPA) procedures that could have been avoided by methodical application of the Revised Geneva Score (RGS) coupled with age-adjusted D-dimer cut-offs rather than only clinical judgment in Emergency Department patients with suspected pulmonary embolism (PE). Material and methods: Between November 2019 and May 2020, 437 patients with suspected PE based on symptoms and D-dimer test were included in this study. All patients underwent to CTPA. For each patient, we retrospectively calculated the age-adjusted D-dimer cut-offs and the RGS in the original version. Finally, CT images were retrospectively reviewed, and the presence of PE was recorded. Results: In total, 43 (9.84%) CTPA could have been avoided by use of RGS coupled with age-adjusted D-dimer cut-offs. Prevalence of PE was 14.87%. From the analysis of 43 inappropriate CTPA, 24 (55.81%) of patients did not show any thoracic signs, two (4.65%) of patients had PE, and the remaining patients had alternative thoracic findings. Conclusion: The study showed good prevalence of PE diagnoses in our department using only physician assessment, although 9.84% CTPA could have been avoided by methodical application of RGS coupled with age-adjusted D-dimer cut-offs