Charged particle therapy—optimization, challenges and future directions

The use of charged particle therapy to control tumours non-invasively offers advantages over conventional radiotherapy. Protons and heavy ions deposit energy far more selectively than X-rays, allowing a higher local control of the tumour, a lower probability of damage to healthy tissue, low risk of complications and the chance for a rapid recovery after therapy. Charged particles are also useful for treating tumours located in areas that surround tissues that are radiosensitive and in anatomical sites where surgical access is limited. Current trial outcomes indicate that accelerated ions can potentially replace surgery for radical cancer treatments, which might be beneficial as the success of surgical cancer treatments are largely dependent on the expertise and experience of the surgeon and the location of the tumour. However, to date, only a small number of controlled randomized clinical trials have made comparisons between particle therapy and X-rays. Therefore, although the potential advantages are clear and supported by data, the cost:benefit ratio remains controversial. Research in medical physics and radiobiology is focusing on reducing the costs and increasing the benefits of this treatment

Multiple Dynamics in Tumor Microenvironment Under Radiotherapy.

The tumor microenvironment (TME) is an evolutionally low-level and embryonically featured tissue comprising heterogenic populations of malignant and stromal cells as well as noncellular components. Under radiotherapy (RT), the major modality for the treatment of malignant diseases [1], TME shows an adaptive response in multiple aspects that affect the efficacy of RT. With the potential clinical benefits, interests in RT combined with immunotherapy (IT) are intensified with a large scale of clinical trials underway for an array of cancer types. A better understanding of the multiple molecular aspects, especially the cross talks of RT-mediated energy reprogramming and immunoregulation in the irradiated TME (ITME), will be necessary for further enhancing the benefit of RT-IT modality. Coming studies should further reveal more mechanistic insights of radiation-induced instant or permanent consequence in tumor and stromal cells. Results from these studies will help to identify critical molecular pathways including cancer stem cell repopulation, metabolic rewiring, and specific communication between radioresistant cancer cells and the infiltrated immune active lymphocytes. In this chapter, we will focus on the following aspects: radiation-repopulated cancer stem cells (CSCs), hypoxia and re-oxygenation, reprogramming metabolism, and radiation-induced immune regulation, in which we summarize the current literature to illustrate an integrated image of the ITME. We hope that the contents in this chapter will be informative for physicians and translational researchers in cancer radiotherapy or immunotherapy