Biological Insights and Radiation-Immuno-Oncology Developments in Primary and Secondary Brain Tumors.
Fabiana GregucciKathryn BealJonathan P S KniselyPaul PagniniAlba FiorentinoElisabetta BonzanoClaire I Vanpouille-BoxBabacar CisseSusan C PannulloPhilip E StiegSylvia C FormentiPublished in: Cancers (2024)
Malignant central nervous system (CNS) cancers include a group of heterogeneous dis-eases characterized by a relative resistance to treatments and distinguished as either primary tumors arising in the CNS or secondary tumors that spread from other organs into the brain. Despite therapeutic efforts, they often cause significant mortality and morbidity across all ages. Radiotherapy (RT) remains the main treatment for brain cancers, improving associated symptoms, improving tumor control, and inducing a cure in some. However, the ultimate goal of cancer treatment, to improve a patient's survival, remains elusive for many CNS cancers, especially primary tumors. Over the years, there have thus been many preclinical studies and clinical trials designed to identify and overcome mechanisms of resistance to improve outcomes after RT and other therapies. For example, immunotherapy delivered concurrent with RT, especially hypo-fractionated stereotactic RT, is synergistic and has revolutionized the clinical management and outcome of some brain tumors, in particular brain metastases (secondary brain tumors). However, its impact on gliomas, the most common primary malignant CNS tumors, remains limited. In this review, we provide an overview of radioresistance mechanisms, the emerging strategies to overcome radioresistance, the role of the tumor microenviroment (TME), and the selection of the most significant results of radiation-immuno-oncological investigations. We also identify novel therapeutic opportunities in primary and secondary brain tumors with the purpose of elucidating current knowledge and stimulating further research to improve tumor control and patients' survival.
Keyphrases
- brain metastases
- blood brain barrier
- small cell lung cancer
- clinical trial
- ejection fraction
- healthcare
- early stage
- resting state
- newly diagnosed
- radiation induced
- palliative care
- risk factors
- oxidative stress
- locally advanced
- dna damage response
- free survival
- radiation therapy
- prognostic factors
- randomized controlled trial
- squamous cell carcinoma
- type diabetes
- stem cells
- chronic kidney disease
- high grade
- depressive symptoms
- drug delivery
- patient reported outcomes
- functional connectivity
- subarachnoid hemorrhage
- physical activity
- cancer therapy
- bone marrow
- open label
- patient reported
- quality improvement
- minimally invasive
- robot assisted
- rectal cancer
- peritoneal dialysis
- sleep quality