Background: The therapeutic potential of proton therapy (PT) was first recognized in 1946 by Robert Wilson, and nowadays, over 100 proton centers are in operation worldwide, and more than 60 are under construction or planned. Bibliometric data can be used to perform a structured analysis of large amounts of scientific data to provide new insights, e.g., to assess the growth and development of the field and to identify research trends and hot topics. The aim of this study is to provide a comprehensive bibliometric analysis of the current status and trends in scientific literature in the PT field. Methods: The literature on PT until the 31st December 2022 in the Scopus database was searched, including the following keywords: proton AND radiotherapy AND cancer/tumor in title, abstract, and/or keywords. The open-source R Studio’s Bibliometrix package and Biblioshiny software (version 2.0) were used to perform the analysis. Results: A total of 7335 documents, mainly articles (n = 4794, 65%) and reviews (n = 1527, 21%), were collected from 1946 to 2022 from 1054 sources and 21,696 authors. Of these, roughly 84% (n = 6167) were produced in the last 15 years (2008–2022), in which the mean annual growth rate was 13%. Considering the corresponding author’s country, 79 countries contributed to the literature; the USA was the top contributor, with 2765 (38%) documents, of whom 84% were single-country publications (SCP), followed by Germany and Japan, with 535 and 531 documents of whom 66% and 93% were SCP. Considering the themes subanalysis (2002–2022), a total of 7192 documents were analyzed; among all keywords used by authors, the top three were radiotherapy (n = 1394, 21% of documents), intensity-modulated radiotherapy (n = 301, 5%), and prostate cancer (n = 301, 5%). Among disease types, prostate cancer is followed by chordoma, head and neck, and breast cancer. The change in trend themes demonstrated the fast evolution of hotspots in PT; among the most recent trends, the appearance of flash, radiomics, relative biological effectiveness (RBE), and linear energy transfer (LET) deserve to be highlighted. Conclusions: The results of the present bibliometric analysis showed that PT is an active and rapidly increasing field of research. Themes of the published works encompass the main aspects of its application in clinical practice, such as the comparison with the actual photon-based standard of care technique and the continuing technological advances. This analysis gives an overview of past scientific production and, most importantly, provides a useful point of view on the future directions of the research activities.

Osteoradionecrosis (ORN) is a serious long-term complication of head and neck radiotherapy (RT), which is often triggered by dental extractions. It results from avascular aseptic necrosis due to irradiated bone damage. ORN is challenging to treat and can lead to severe complications. Furthermore, ORN causes pain and distress, significantly reducing the patient’s quality of life. There is currently no established preventive strategy. This narrative review aims to provide an update for the clinicians on the risk of ORN associated with oral surgery in head and neck RT patients, with a focus on the timing suitable for the oral surgery and possible ORN preventive treatments. An electronic search of articles was performed by consulting the PubMed database. Intervention and observational studies were included. A multidisciplinary approach to the patient is highly recommended to mitigate the risk of RT complications. A dental visit before commencing RT is highly advised to minimize the need for future dental extractions after irradiation, and thus the risk of ORN. Post-RT preventive strategies, in case of dento-alveolar surgery, have been proposed and include antibiotics, hyperbaric oxygen (HBO), and the combined use of pentoxifylline and tocopherol (“PENTO protocol”), but currently there is a lack of established standards of care. Some limitations in the use of HBO involve the low availability of HBO facilities, its high costs, and specific clinical contraindications; the PENTO protocol, on the other hand, although promising, lacks clinical trials to support its efficacy. Due to the enduring risk of ORN, removable prostheses are preferable to dental implants in these patients, as there is no consensus on the appropriate timing for their safe placement. Overall, established standards of care and high-quality evidence are lacking concerning both preventive strategies for ORN as well as the timing of the dental surgery. There is an urgent need to improve research for more efficacious clinical decision making.

The number of Proton Therapy (PT) facilities is still limited worldwide, and the access to treatment could be characterized by patients’ logistic and economic challenges. Aim of the present survey is to assess the support provided to patients undergoing PT across Europe. Through a personnel contact, an online questionnaire (62 multiple-choice and open-ended questions) via Microsoft Forms was administered to 10 European PT centers. The questionnaire consisted of 62 questions divided into 6 sections: i) personal data; ii) general information on clinical activity; iii) fractionation, concurrent systemic treatments and technical aspects of PT facility; iv) indication to PT and reimbursement policies; v) economic and/ or logistic support to patients vi) participants agreement on statements related to the possible limitation of access to PT. A qualitative analysis was performed and reported. From March to May 2022 all ten involved centers filled the survey. Nine centers treat from 100 to 500 patients per year. Paediatric patients accounted for 10–30%, 30–50% and 50–70% of the entire cohort for 7, 2 and 1 center, respectively. The most frequent tumours treated in adult population were brain tumours, sarcomas and head and neck carcinomas; in all centers, the mean duration of PT is longer than 3 weeks. In 80% of cases, the treatment reimbursement for PT is supplied by the respective country’s Health National System (HNS). HNS also provides economic support to patients in 70% of centers, while logistic and meal support is provided in 20% and 40% of centers, respectively. PT facilities offer economic and/or logistic support in 90% of the cases. Logistic support for parents of pediatric patients is provided by HNS only in one-third of centers. Overall, 70% of respondents agree that geographic challenges could limit a patient’s access to proton facilities and 60% believe that additional support should be given to patients referred for PT care. Relevant differences exist among European countries in supporting patients referred to PT in their logistic and economic challenges. Further efforts should be made by HNSs and PT facilities to reduce the risk of inequities in access to cancer care with protons.

Purpose or Objective—The aim of the study is to evaluate the efficacy and safety of SBRT on detectable prostate bed recurrence in RT-naïve prostate cancer patients. Materials and methods: Eighty-six patients who underwent SBRT for macroscopic bed recurrence after prostatectomy were retrospectively included. Patients were treated based on mpMRI or choline/PSMA PET. Results: The median time to biochemical relapse (BCR) after RP was 46 months, with a median PSA at restaging of 1.04 ng/mL. Forty-six patients were staged with mpMRI and choline/PSMA PET, while ten and thirty were treated based on PET and MRI only, respectively. Only one late G ≥ 2 GI toxicity was observed. With a median BCR follow-up of 14 months, twenty-nine patients experienced a BCR with a median PSA at recurrence of 1.66 ng/mL and a median survival free from the event of 40.1 months. The median time to BCR was 17.9 months. Twenty-seven patients had clinical relapse (CR), with a median CR follow-up of 16.27 months and a median time to CR of 23.0 months. Biochemical recurrence-free survival at one and two years was 88% and 66%, respectively, while clinical recurrence-free survival at one and two years was 92% and 82%, respectively. Regarding local relapses, seven were in the field of treatment, while eight of them were outside the field of treatment. Conclusions: Data showed that SBRT targeting only the macroscopic bed recurrence instead of the whole prostate bed is safe and effective. Additional data and longer follow-ups will provide a clearer indication of the appropriate treatment and staging methodology for these patients.

In this technical development report, we present the strategic placement of fiducial markers within the prostate under the guidance of computed tomography (CT) and electromagnetic navigation (EMN) for the delivery of ultra-hypofractionated cyberknife (CK) therapy in a patient with localized prostate cancer (PCa) who had previously undergone chemo-radiotherapy for rectal cancer and subsequent abdominoperineal resection due to local recurrence. The patient was positioned in a prone position with a pillow under the pelvis to facilitate access, and an electromagnetic fiducial marker was placed on the patient’s skin to establish a stable position. CT scans were performed to plan the procedure, mark virtual points, and simulate the needle trajectory using the navigation system. Local anesthesia was administered, and a 21G needle was used to place the fiducial markers according to the navigation system information. A confirmatory CT scan was obtained to ensure proper positioning. The implantation procedure was safe, without any acute side effects such as pain, hematuria, dysuria, or hematospermia. Our report highlights the ability to use EMN systems to virtually navigate within a pre-acquired imaging dataset in the interventional room, allowing for non-conventional approaches and potentially revolutionizing fiducial marker positioning, offering new perspectives for PCa treatment in selected cases.

In this paper, we aim to evaluate the entity of inter-fraction organ motion and deformation in stereotactic body radiotherapy (SBRT) treatments for nodal oligometastatic prostate cancer (PCa). Thirty-three patients with lymph nodes showing oligometastatic PCa treated with SBRT were included. Organs at risk (OARs) were delineated using both simulation computer tomography (s-CT) and daily cone beam CTs (CBCTs) using the Raystation planning system. For each OAR, the union volume (UV) between all the CBCTs and s-CT was computed. An expanded volume (EV) of the s-CT OARs was applied using six different margins (3, 5, 8, 10, 15, and 20 mm). A percentage volume (V%) was computed to assess the intersection between each EV and UV. The OAR deformation and motion were further evaluated using the dice similarity coefficient (DSC) and mean distance to agreement (Mean_DA). The percentage maximum dose variations for all the OARs were estimated. A recalculation with higher dose prescriptions was performed by prescribing 36 Gy/3 fx, as well as 45 Gy/3 fx. The cauda showed the highest matching (DSC = 0.72; Mean_DA = 0.14 cm), and the colon showed the lowest one (DSC = 0.37; Mean_DA = 0.44 cm). The minimum margin, which ensured a V% > 95%, was 3 mm (97.5%) for the cauda and 15 mm (96.6%) for the colon. All the OARs reached the compliance of the constraints in each session. Regarding 36 Gy-plans, the ileum punctual compliance Dmax failed in 58.8% of patients, and it failed in 70.6% of the patients for the ileum, 7.14% for the colon, and 12.5% for the bladder in the case of 45 Gy-plans. This study is an ancillary study of the RADIOSA clinical trial (AIRC IG-22159) and can be used as a benchmark for dose escalation.