UNASSIGNED: Although access to proton beam therapy (PBT) is limited worldwide, its use for the treatment of hepatocellular carcinoma (HCC) is gradually increasing with the expansion of new facilities. Therefore, we conducted a systematic review and meta-analysis to investigate the updated evidence of PBT for HCC.
UNASSIGNED: The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched for studies that enrolled patients with liver-confined HCC that were treated with PBT for a cure up to February 2024.
UNASSIGNED: A total of 1858 HCC patients receiving PBT from 22 studies between 2004 and 2023 were selected for this meta-analysis. The median proportion of Child-Pugh class A was 86% (range: 41-100%), and the median tumor size was 3.6 cm (range: 1.2-9 cm). The median total dose ranged from 55 GyE to 76 GyE (median, 69 GyE). The pooled rates of 3- and 5-year local progression-free survival after PBT were 88% (95% confidence interval [CI], 85-91%) and 86% (95% CI, 82-90%), respectively. The pooled 3- and 5-year overall rates were 60% (95% CI, 54-66%) and 46% (95% CI, 38-54%), respectively. The pooled rates of grade 3 hepatic toxicity, classic radiation-induced liver disease (RILD), and non-classic RILD were 1%, 2%, and 1%, respectively.
UNASSIGNED: The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other radiotherapy modalities. However, further studies are needed to identify the subgroups that will benefit from PBT.

Proton therapy has emerged as a crucial tool in the treatment of head and neck and skull-base cancers, offering advantages over photon therapy in terms of decreasing integral dose and reducing acute and late toxicities, such as dysgeusia, feeding tube dependence, xerostomia, secondary malignancies, and neurocognitive dysfunction. Despite its benefits in dose distribution and biological effectiveness, the application of proton therapy is challenged by uncertainties in its relative biological effectiveness (RBE). Overcoming the challenges related to RBE is key to fully realizing proton therapy\'s potential, which extends beyond its physical dosimetric properties when compared with photon-based therapies. In this paper, we discuss the clinical significance of RBE within treatment volumes and adjacent serial organs at risk in the management of head and neck and skull-base tumors. We review proton RBE uncertainties and its modeling and explore clinical outcomes. Additionally, we highlight technological advancements and innovations in plan optimization and treatment delivery, including linear energy transfer/RBE optimizations and the development of spot-scanning proton arc therapy. These advancements show promise in harnessing the full capabilities of proton therapy from an academic standpoint, further technological innovations and clinical outcome studies, however, are needed for their integration into routine clinical practice.

OBJECTIVE: To demonstrate a framework for calculating daily dose distributions for proton therapy in a timeframe amenable to online evaluation using CT-on-Rails.
METHODS: Tasks associated with calculation of daily dose are fully automated. A rigid registration between daily and planning images is used to propagate beams and targets for calculation of daily dose; additionally, risk structures are propagated using deformable registration to facilitate online evaluation. An end-to-end constancy test was carried out using a pelvis phantom containing a simulated target and bladder contour. 97 Daily fan-beam CT data sets associated with 10 clinical patients were processed to demonstrate feasibility and utility of online evaluation. Computing times and dosimetric differences are reported.
RESULTS: The phantom constancy test took 62 s to complete with no notable discrepancies in the registrations or calculated dose. Max doses were identical for target and bladder contours on initial and repeat scans (359 and 310 cGy (RBE) respectively). Total processing time for 97 daily patient images averaged 154.6 s (73.0 - 222.0 s; SD = 31.8 s). On average, dose calculation accounted for 35 % of total processing time. Average differences in D95 for target contours was 1.5 % (SD = 1.6 %) with a max decrease of 5.9 % on a single daily image.
CONCLUSIONS: Daily dose can be automatically calculated in a timeframe amenable to online evaluation using scanner utilities in conjunction with the scripting API of a commercial treatment planning system. Online evaluation of dose in proton therapy is useful to detect clinically relevant changes, guide setup, and facilitate treatment or replanning decisions.

Compared to conventional radiotherapy using X-rays, proton therapy, in principle, allows better conformity of the dose distribution to target volumes, at the cost of greater sensitivity to physical, anatomical, and positioning uncertainties. Robust planning, both in terms of plan optimization and evaluation, has gained high visibility in publications on the subject and is part of clinical practice in many centers. However, there is currently no consensus on the methods and parameters to be used for robust optimization or robustness evaluation. We propose to overcome this deficiency by following the modified Delphi consensus method. This method first requires a systematic review of the literature. We performed this review using the PubMed and Web Of Science databases, via two different experts. Potential conflicts were resolved by a third expert. We then explored the different methods before focusing on clinical studies that evaluate robustness on a significant number of patients. Many robustness assessment methods are proposed in the literature. Some are more successful than others and their implementation varies between centers. Moreover, they are not all statistically or mathematically equivalent. The most sophisticated and rigorous methods have seen more limited application due to the difficulty of their implementation and their lack of widespread availability.

Purpose: Head and neck adenoid cystic carcinoma (HNACC) is a radioresistant tumor. Particle therapy, primarily proton beam therapy and carbon-ion radiation, is a potential radiotherapy treatment for radioresistant malignancies. This study aims to conduct a meta-analysis to evaluate the impact of charged particle radiation therapy on HNACC. Methods: A comprehensive search was conducted in Pubmed, Cochrane Library, Web of Science, Embase, and Medline until December 31, 2022. The primary endpoints were overall survival (OS), local control (LC), and progression-free survival (PFS), while secondary outcomes included treatment-related toxicity. Version 17.0 of STATA was used for all analyses. Results: A total of 14 studies, involving 1297 patients, were included in the analysis. The pooled 5-year OS and PFS rates for primary HNACC were 78% (95% confidence interval [CI] = 66-91%) and 62% (95% CI = 47-77%), respectively. For all patients included, the pooled 2-year and 5-year OS, LC, and PFS rates were as follows: 86.1% (95% CI = 95-100%) and 77% (95% CI = 73-82%), 92% (95% CI = 84-100%) and 73% (95% CI = 61-85%), and 76% (95% CI = 68-84%) and 55% (95% CI = 48-62%), respectively. The rates of grade 3 and above acute toxicity were 22% (95% CI = 13-32%), while late toxicity rates were 8% (95% CI = 3-13%). Conclusions: Particle therapy has the potential to improve treatment outcomes and raise the quality of life for HNACC patients. However, further research and optimization are needed due to the limited availability and cost considerations associated with this treatment modality.

UNASSIGNED: This systematic review study investigated the cost-effectiveness of stereotactic radiotherapy (SRT) and stereotactic radiosurgery (SRS) for treatment of various types of cancers.
UNASSIGNED: PubMed, Scopus, and Web of Science were searched from 30 December 1990 to 1 January 2023. The entered studies were screened in accordance with the inclusion criteria. The inclusion criteria encompassed all types of economic evaluation studies that investigated SRT/SRS technologies in the treatment of various cancers.
UNASSIGNED: A total of 47 articles were included in the review. The findings suggest that the use of Linear accelerator technology for the treatment of lung cancer (8 out of 12 studies) and prostate cancer (4 out of 5 studies) was a cost-effective strategy. Linear accelerator was found to be cost-effective in the treatment of liver metastases and liver cancer (2 out of 5 studies). All of the included studies that used Gamma Knife technology in brain metastases reported Gamma-Knife was a cost-effective treatment. Furthermore, in the treatment of prostate and liver cancer, proton therapy was identified as a cost-effective option than other treatments.
UNASSIGNED: This study confirms that SRT/SRS is a cost-effective procedure for the treatment of various types of cancers. Therefore, it is recommended to use SRT/SRS technology for optimal use of resources.

Proton beam therapy (PBT) has great advantages as tumor radiotherapy and is progressively becoming a more prevalent choice for individuals undergoing radiation therapy. The objective of this review is to pinpoint collaborative efforts among countries and institutions, while also exploring the hot topics and future outlook in the field of PBT. Data from publications were downloaded from the Web of Science Core Collection. CiteSpace and Excel 2016 were used to conduct the bibliometric and knowledge map analysis. A total of 6516 publications were identified, with the total number of articles steadily increasing and the United States being the most productive country. Harvard University took the lead in contributing the highest number of publications. Paganetti Harald published the most articles and had the most cocitations. PHYS MED BIOL published the greatest number of PBT-related articles, while INT J RADIAT ONCOL received the most citations. Paganetti Harald, 2012, PHYS MED BIOL can be classified as classic literature due to its high citation rate. We believe that research on technology development, dose calculation and relative biological effectiveness were the knowledge bases in this field. Future research hotspots may include clinical trials, flash radiotherapy, and immunotherapy.

BACKGROUND: Ocular surface disorder after ocular radiation therapy, even though commonly reported, is often overlooked. Any delay in diagnosis may lead to complications that threaten vision. The presented case highlights the clinical outcome of a severe post-radiation disorder of the ocular surface, the importance of intensive therapy, and the limitations of further surgical interventions.
METHODS: A 34-year-old woman was referred for a second opinion due to a years-long history of pain and redness in her right eye (OD) after proton beam therapy for recurrent iris melanoma. The patient then developed post-radiation retinopathy with macula edema, secondary glaucoma, cataract, as well as a severe ocular surface disorder with corneal decompensation and band keratopathy. Several surgical treatments have been attempted, including phacoemulsification with IOL implantation and trabeculectomy with mitomycin C. Due to refractory glaucoma, Baerveldt glaucoma drainage was then necessary. Given the worsening clinical presentation of post-radiation ocular surface disorder with progressing band keratopathy, the possibility of penetrating keratoplasty (PKP) was discussed.
CONCLUSIONS: The continuous worsening of clinical symptoms of the disorder of the ocular surface after proton beam radiotherapy can be the result of a post-radiation syndrome. Gradual expansion of ischemia, vasculitis, and inflammatory mediators compresses the retinal tissue, leading to recurrent macular edema as well as to secondary glaucoma and corneal decompensation. Band keratopathy is occasionally noted and seems to result from severe post-radiation disorder of the ocular surface. However, PKP would typically be indicated in cases of corneal perforation, uncontrolled infectious keratitis, or for improving vision in the presence of corneal opacification, none of which applied to our patient. Furthermore, post-radiation keratopathy implies compromised corneal stromal lymphogenesis and angiogenesis, both of which are now considered essential conditions for allograft rejection. Moreover, a previously performed Baerveldt glaucoma drainage surgery can affect the survival rate of the endothelial cells of the recipient cornea. Therefore, a penetrating or endothelial keratoplasty should be viewed as a high-risk procedure. In this instance, the rigorous treatment of the severe ocular surface disorder was crucial. We managed our patient\'s complex situation by following the latest guidelines set by the Tear Film & Ocular Surface Society and aimed to alleviate the symptoms as effectively as possible. In conclusion, careful decision-making regarding surgical treatment options should be considered, taking into account the complexities and potential risks involved.
Eine 34-jährige Frau wurde wegen Schmerzen und Rötungen am rechten Auge seit Jahren überwiesen. Ihre Krankengeschichte ergab eine Exzision eines Irismelanoms im Alter von 29 Jahren. Aufgrund eines Rezidivs wurde daraufhin eine Protonenstrahlentherapie durchgeführt. Infolgedessen entwickelte die Patientin nach der Strahlentherapie eine Retinopathie mit Makulaödem, sekundärem Glaukom, Katarakt sowie einer schweren Störung der Augenoberfläche mit Hornhautdekompensation und einer Bandkeratopathie. Es wurden mehrere chirurgische Eingriffe unternommen, darunter die Phakoemulsifikation mit IOL-Implantation und die Trabekulektomie mit Mitomycin C. Aufgrund des refraktären Glaukoms war schließlich auch eine Baerveldt-Implantation erforderlich. Trotz vielfältiger therapeutischer Ansätzen zur Befeuchtung zeigte sich keine Verbesserung des Problems der Augenoberfläche. Aufgrund der Verschlechterung der klinischen Präsentation der Augenoberflächenstörung wurde die Möglichkeit einer perforierenden Keratoplastik in Betracht gezogen. Es bleibt jedoch fraglich, ob solche Patienten von einer perforierenden Keratoplastik profitieren würden, da die resultierende Lymph- und Hämangiogenese des Hornhautstromas wesentliche Risikofaktoren für die Abstoßung von Fremdgewebe darstellen.

The aim of this systematic review is to determine whether Deep Learning (DL) algorithms can provide a clinically feasible alternative to classic algorithms for synthetic Computer Tomography (sCT). The following categories are presented in this study: ∙ MR-based treatment planning and synthetic CT generation techniques. ∙ Generation of synthetic CT images based on Cone Beam CT images. ∙ Low-dose CT to High-dose CT generation. ∙ Attenuation correction for PET images. To perform appropriate database searches, we reviewed journal articles published between January 2018 and June 2023. Current methodology, study strategies, and results with relevant clinical applications were analyzed as we outlined the state-of-the-art of deep learning based approaches to inter-modality and intra-modality image synthesis. This was accomplished by contrasting the provided methodologies with traditional research approaches. The key contributions of each category were highlighted, specific challenges were identified, and accomplishments were summarized. As a final step, the statistics of all the cited works from various aspects were analyzed, which revealed that DL-based sCTs have achieved considerable popularity, while also showing the potential of this technology. In order to assess the clinical readiness of the presented methods, we examined the current status of DL-based sCT generation.

BACKGROUND: Atezolizumab/bevacizumab combination therapy became the first-line therapy for advanced hepatocellular carcinoma (HCC). Gastroesophageal varices should be monitored and managed before treatment. The progression of portal hypertension during bevacizumab-containing therapy is unclear.
METHODS: A case of new development of esophageal varices, ascites, and hepatic hydrothorax during atezolizumab/bevacizumab therapy at National Taiwan University Hospital was reported, and relevant literature was reviewed.
RESULTS: We presented an 83-year-old male with resolved hepatitis B without cirrhosis. He had BCLC stage C HCC and received tri-weekly atezolizumab/bevacizumab therapy for 34 cycles with sustained partial response. Progressive ascites, esophageal varices, and hepatic hydrothorax developed, though his portal vein was patent and the tumor was under control. Five similar cases of HCC (BCLC B/C: n = 3/2) had been reported previously. Among them, three had cirrhosis with pre-existing small esophageal varices before treatment. After the administration of 1-15 cycles of atezolizumab/bevacizumab therapy, one patient had a progression of varices, and the other four developed variceal bleeding. The association between atezolizumab/bevacizumab and portal hypertension was possible, which might relate to the VEGF pathway and immune-related adverse events with progressive hepatic fibrosis.
CONCLUSIONS: Atezolizumab/bevacizumab treatment might exacerbate portal hypertension. Careful monitoring and management should be considered during treatment.