Proton minibeam radiotherapy (pMBRT) is an external beam radiotherapy method with reduced side effects by taking advantage of spatial fractionation in the normal tissue. Due to scattering, the delivered small beams widen in the tissue ensuring a homogeneous dose distribution in the tumor. In this review, the physical and biological principles regarding dose distribution and healing effects are explained. In the last decade, several preclinical studies have been conducted addressing normal tissue sparing and tumor control in-vitro and in-vivo, using human skin tissue and mouse or rat models. The major results acquired in these studies are summarized. A further newly emerging therapy method is FLASH radiotherapy, i.e. the treatment using ultra-high dose rates. The possibility of combining these methods in proton minibeam FLASH therapy (pMB FLASH) is worked out. Additionally, technical feasibility and limitations will be discussed by looking at simulations as well as preclinical studies and also pointing out new ways of delivering the desired tumor dose, such as interlacing. We will also highlight the opportunities that emerge regarding high dose radiation, hypofractionation and the combination with immunotherapy.

Cervix uteri carcinoma is the most common gynecological cancer worldwide. In addition, it is the fourth most common malignancy and the fourth leading cause of cancer-related death in women [1]. The most common histopathological subtype is squamous cell carcinoma (85%).

Head and neck squamous cell carcinomas (HNSCCs) are a group of aggressive and genetically complex cancers, derived from the mucosal epithelium in the oral cavity, pharynx, and larynx. Radiotherapy, often combined with chemotherapy remains the mainstay treatment options for patients.