Outcomes of Patients Treated in the UK Proton Overseas Programme: Central Nervous System Group.

AIMS: In 2008, the UK National Health Service started the Proton Overseas Programme (POP), to provide access for proton beam therapy (PBT) abroad for selected tumour diagnoses while two national centres were being planned. The clinical outcomes for the patient group treated for central nervous system (CNS), base of skull, spinal and paraspinal malignancies are reported here. MATERIALS AND METHODS: Since the start of the POP, an agreement between the National Health Service and UK referring centres ensured outcomes data collection, including overall survival, local tumour control and late toxicity data. Clinical and treatment-related data were extracted from this national patient database. Grade ≥3 late toxicities were reported following Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 definition, occurring later than 90 days since the completion of treatment. RESULTS: Between 2008 and September 2020, 830 patients were treated within the POP for the above listed malignancies. Overall survival data were available for 815 patients and local control data for 726 patients. Toxicity analysis was carried out on 702 patients, with patients excluded due to short follow-up (<90 days) and/or inadequate toxicity data available. After a median follow-up of 3.34 years (0.06-11.58), the overall survival was 91.2%. The local control rate was 85.9% after a median follow-up of 2.81 years (range 0.04-11.58). The overall grade ≥3 late toxicity incidence was 11.97%, after a median follow-up of 1.72 years (0.04-8.45). The median radiotherapy prescription dose was 54 GyRBE (34.8-79.2). CONCLUSIONS: The results of this study indicate the safety of PBT for CNS tumours. Preliminary clinical outcomes following PBT for paediatric/teen and young adult and adult CNS tumours treated within the POP are encouraging, which reflects accurate patient selection and treatment quality. The rate of late effects compares favourably with published cohorts. Clinical outcomes from this patient cohort will be compared with those of UK-treated patients since the start of the national PBT service in 2018.

Normal Tissue Complication Probability Modelling for Toxicity Prediction and Patient Selection in Proton Beam Therapy to the Central Nervous System: A Literature Review.

Normal tissue complication probability (NTCP) models can guide clinical decision making in radiotherapy. In recent years, they have been used for patient selection for proton beam therapy (PBT) for some anatomical tumour sites. This review synthesizes the published evidence regarding the use of NTCP models to predict the toxicity of PBT, for different end points in patients with brain tumours. A search of Medline and Embase using the Patients, Intervention, Comparison, Outcome (PICO) criteria was undertaken. In total, 37 articles were deemed relevant and were reviewed in detail. Nineteen articles on NTCP modelling of toxicity end points were included. Of these, 11 were comparative NTCP studies of PBT versus conventional photon radiotherapy (XRT), which evaluated differences in plan dosimetry and then assumed that XRT-derived literature estimates of NTCP would be applicable to both. Seven papers derived NTCP models based on PBT outcome data, two of which provided model parameters. Among analysed end points, the reduced risk of secondary tumours with PBT as compared with XRT is estimated - through modelling studies - to be considerable and was highlighted by most authors. For other analysed end points, the clinical benefit of PBT mainly depends on tumour location in relation to organs at risk as well as prescription doses. NTCP models can be useful tools for treatment plan comparison. However, most published toxicity data were derived from XRT cohorts; this review has highlighted the need for further studies relating dose-volume parameters to observed toxicity in PBT-treated patients. Specifically, there is a need for PBT-specific NTCP models that can be implemented in the clinical practice. NTCP models built on robust clinical data for the most common radiotherapy toxicities in the brain would potentially redefine the current indications for PBT.

Skin Toxicity Profile of Photon Radiotherapy versus Proton Beam Therapy in Paediatric and Young Adult Patients with Sarcomas.

AIMS: Radiotherapy is key in the management of patients with both Ewing sarcoma and rhabdomyosarcoma. However, there is little evidence in the literature with regards to radiation-induced skin toxicities (RISTs) for patients treated with conventional radiotherapy with X-rays (XRT) or proton beam therapy (PBT) for these two conditions. In the present study we evaluated acute and late RIST in patients treated within European protocols with either PBT or XRT, taking both clinical and dosimetric variables into consideration. MATERIALS AND METHODS: This was a retrospective analysis of 79 paediatric/young adult patients treated with radical radiotherapy (with XRT or PBT) and concurrent chemotherapy. In all cases, radiotherapy was given in conventional fractionation (1.8 Gy/fraction). Acute and late RISTs were registered according to the Radiation Therapy Oncology Group (RTOG) scoring system. RESULTS: With regards to acute RIST, 47.9% (23/48) of XRT patients and 48.4% (15/31) of PBT patients had acute grade 2/3 toxicity. When it comes to late RIST, 17.5% (7/40 with known toxicity profile) of XRT patients and 29.0% (9/31) of PBT patients had grade 1/2 toxicity. This difference of -11.5% (95% confidence interval -31.2 to 7.9%) in grade 1/2 toxicity between XRT and PBT was not statistically significant (P = 0.25). Regardless of the radiotherapy technique, V30Gy seems a good predictor of acute RIST. Moreover, for the same value of V30Gy, patients who receive PBT may have a higher risk of moderate-severe acute RIST. Perhaps due to the small sample, definitive conclusions on the predictive factors of late RIST could not be drawn. CONCLUSIONS: No clinically meaningful differences in acute and late RIST were observed between PBT and XRT subgroups. Systematic differences in the modelling of the build-up region may exist between XRT and PBT algorithms, which could make the comparison of dose metrics between techniques potentially biased. A more comprehensive analysis of dosimetric data on larger patient cohorts is needed to elucidate the most relevant skin dose metrics. Dose-effect models of RIST for this unique patient population would be an invaluable tool in radiotherapy plan optimisation.

Imaging changes in very young children with brain tumors treated with proton therapy and chemotherapy.

SUMMARY: PT promises to reduce side effects in children with brain tumors by sparing normal tissue compared with 3D conformal or intensity-modulated radiation therapy. Information is lacking about the combined effects of PT and chemotherapy in young children. We describe imaging changes in 8 very young children with localized brain tumors who received PT after chemotherapy. Mostly transient signal abnormalities and enhancement in brain parenchyma were observed by serial MR imaging, which were consistent with radiation-induced effects on normal-appearing tissue. Correlation with PT planning data revealed that the areas of imaging abnormality were located within or adjacent to the volume that received the highest radiation dose. Radiologists should be aware of these findings in children who receive PT after chemotherapy. In this report, we describe the time course of these PT-related imaging findings and correlate them with treatment and clinical outcomes.

Virtual reality in surgical training.

Virtual reality in surgery and, more specifically, in surgical training, faces a number of challenges in the future. These challenges are building realistic models of the human body, creating interface tools to view, hear, touch, feel, and manipulate these human body models, and integrating virtual reality systems into medical education and treatment. A final system would encompass simulators specifically for surgery, performance machines, telemedicine, and telesurgery. Each of these areas will need significant improvement for virtual reality to impact medicine successfully in the next century. This article gives an overview of, and the challenges faced by, current systems in the fast-changing field of virtual reality technology, and provides a set of specific milestones for a truly realistic virtual human body.