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Kaplan-Meier plots showing correlation between hypoxia and glycolysis PET parameters and progression-free survival. (a) FDG SUVmax (p = 0.09); (b) FMISO SUVmax (p = 0.06); (c) FDG TGV (p = 0.12); (d) FMISO TNR (p = 0.02)
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Purpose
Hypoxia is associated with aggressive tumour behaviour and can influence response to systemic therapy and radiotherapy. The prevalence of hypoxia in metastatic colorectal cancer is poorly understood, and the relationship of hypoxia to patient outcomes has not been clearly established. The aims of the study were to evaluate hypoxia in metast...
Citations
... Over 50% of patients with cancer receive radiotherapy for curative or palliative purposes [2]. However, radiotherapy toxicity can impact patients' quality of life and treatment effectiveness [3][4][5][6][7]. Exploring strategies to support patients' conditions is paramount in clinical oncology. ...
Background/Objectives: ACEIs protect against radiation pneumonitis by reducing angiotensin II production, oxidative stress, and inflammation. This study highlights the significance of concurrent angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) use in radiotherapy by evaluating its impact on radiotherapy-related side effects and survival outcomes, addressing the gap in existing research and providing insights to guide clinical practice in oncology. Methods: The literature was retrieved from the MEDLINE, EMBASE, Web of Science, and Scopus databases from January 2000 to October 2024. Studies on adults (≥18 years) with histologically confirmed cancer, receiving ACEIs or ARBs during radiotherapy, were included. Radiotherapy-related side effects and clinical outcomes were analysed using odds ratios (ORs) and 95% confidence intervals (95%CIs), comparing ACEI/ARB users to non-users. Differences in the median survival time, recurrence, and death rates were also calculated. Results: Sixteen studies (14 cohort studies and two randomised trials) were included. ACEI users exhibited a 50% reduction in the risk of ≥grade 2 radiation pneumonitis (OR: 0.50, 95%CI: 0.32–0.77) in lung cancer and significant reductions in the odds of proctitis (80%, OR: 0.20, 95%CI: 0.12–0.33), haematuria (75%, OR: 0.25, 95%CI: 0.16–0.41), and rectal bleeding (61%, OR: 0.39, 95%CI: 0.30–0.51) in prostate cancer. ACEI/ARB users showed reduced symptomatic radiation necrosis in brain metastases and better 6-month functional independence in supratentorial glioblastoma. Among six studies reporting survival, ACEI/ARB users had longer median survival in early-stage non-small-cell lung cancer and glioblastoma but shorter survival in small cell lung cancer and brain metastases. ARB users had inconsistent survival rates for lung cancer. The varying survival outcomes suggest that ACEIs/ARBs have different effects depending on the cancer type and stage, potentially influenced by cancer-specific factors, treatment protocols, or disease progression. Conclusions: ACEI use is associated with a reduction in radiation pneumonitis, but evidence for other radiotherapy-related toxicity and survival outcomes remains inconsistent across cancer types and severities. Further research should carefully control for confounders.
... Chemotherapy is one major treatment for malignancy, but the actual effects and responses to it are confined to drug distributions and immune milieu in tumor [2]. Similarly, radiotherapy efficacy has also been confronted with the resistance caused by tumor hypoxia [3]. While as one common targeted drug-tyrosine kinase inhibitors have also raised people's concerns due to its cardiovascular toxicity, like hypertension, heart failure and arrhythmia [4,5]. ...
Hypertension is one of the most prevalent diseases in cardiology. The angiotensin receptor blockers (ARBs)/angiotensin converting enzyme inhibitors (ACEIs) are widely used drugs to stabilize the blood pressure via inhibition of the renin-angiotensin system (RAS). Studies have found that the exposure to RAS inhibitors (RASi) can suppress the development of cancers via multimodal mechanisms and has attracted increased attentions in the recent past. Owing the potential of RASi to inhibit tumor growth, proliferation and metastasis, they are considered as the potential and exciting candidates to enhance the effect of chemo-radiotherapy and targeted therapy efficacy. However, there are conflicting reports as to the use of ARB/ACEI in all facets of tumor growth. In this study, we comprehensively summarize and review the potential mechanisms of RASi in cancer treatment, like inhibition of tumor angiogenesis, reduction of cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM), regulation of immune cells and improvement of hypoxia. Additionally, based on the basic and clinical experiments, we analyze the views and results regarding the role of RASi plays in tumor from genesis to recurrence, and certainly cancer treatment (chemo-radiotherapy and targeted therapy). In the last, not only do we discuss the prospects of using RASi to enhance cancer treatment efficacy but also point out the conflicting situation with the intention to give some directions and inspiration on this topic.
Colorectal cancer (CRC) is the fourth most frequent cancer worldwide and the most frequently diagnosed cancer in Europe. Although its incidence is increasing, mortality has decreased in the more developed countries, principally due to the improvement of treatment options and to prevention screening allowing earlier diagnosis. In the decision-making process of patients with CRC, a multidisciplinary board of specialists must be involved in which the nuclear medicine physician plays an important role. [18F]FDG PET/CT is the most widely used diagnostic nuclear medicine technique in oncology, and its usefulness has been proven also in the management of patients with CRC. According to the most recent guidelines, the role of [18F]FDG PET/CT is recognized as appropriate in restaging patients with suspected recurrence of CRC, in patients with elevated serum tumor markers such as CEA and a negative or inconclusive standard-diagnostic workup, or for presurgical evaluation of patients with recurrent disease and potentially resectable metastatic lesions. [18F]FDG PET/CT in CRC holds promise for systematic follow-up and for evaluation of response to therapy, especially in the evaluation of chemoradiation therapy in metastatic cancer (late and early response) or of local treatment efficacy with, e.g., radiofrequency ablation of liver metastases. The aim of this chapter is to review the available scientific evidence on the role of nuclear medicine imaging in CRC patients, with special emphasis on the guidelines and recommendations of the main international scientific associations regarding this disease.
Colorectal liver metastases (CRLM) have heterogenous histopathological and immunohistochemical phenotypes, which are associated with variable responses to treatment and outcomes. However, this information is usually only available after resection, and therefore of limited value in treatment planning. Improved techniques for in vivo disease assessment, which can characterise the variable tumour biology, would support further personalization of management strategies. Advanced imaging of CRLM including multiparametric MRI and functional imaging techniques have the potential to provide clinically-actionable phenotypic characterisation. This includes assessment of the tumour-liver interface, internal tumour components and treatment response. Advanced analysis techniques, including radiomics and machine learning now have a growing role in assessment of imaging, providing high-dimensional imaging feature extraction which can be linked to clinical relevant tumour phenotypes, such as a the Consensus Molecular Subtypes (CMS). In this review, we outline how imaging techniques could reproducibly characterize the histopathological features of CRLM, with several matched imaging and histology examples to illustrate these features, and discuss the oncological relevance of these features. Finally, we discuss the future challenges and opportunities of CRLM imaging, with a focus on the potential value of advanced analytics including radiomics and artificial intelligence, to help inform future research in this rapidly moving field.
Angiogenesis is an active process, regulating new vessel growth, and is crucial for the survival and growth of tumours next to other complex factors in the tumour microenvironment. We present possible molecular imaging approaches for tumour vascularisation and vitality, focusing on radiopharmaceuticals (tracers). Molecular imaging in general has become an integrated part of cancer therapy, by bringing relevant insights on tumour angiogenic status. After a structured PubMed search, the resulting publication list was screened for oncology related publications in animals and humans, disregarding any cardiovascular findings. The tracers identified can be subdivided into direct targeting of angiogenesis (i.e., vascular endothelial growth factor, laminin, and fibronectin) and indirect targeting (i.e., glucose metabolism, hypoxia, and matrix metallo-proteases, PSMA). Presenting pre-clinical and clinical data of most tracers proposed in the literature, the indirect targeting agents are not 1:1 correlated with angiogenesis factors but do have a strong prognostic power in a clinical setting, while direct targeting agents show most potential and specificity for assessing tumour vascularisation and vitality. Within the direct agents, the combination of multiple targeting tracers into one agent (multimers) seems most promising. This review demonstrates the present clinical applicability of indirect agents, but also the need for more extensive research in the field of direct targeting of angiogenesis in oncology. Although there is currently no direct tracer that can be singled out, the RGD tracer family seems to show the highest potential therefore we expect one of them to enter the clinical routine.