Dental management in head and neck cancers: from intensity-modulated radiotherapy with photons to proton therapy.

INTRODUCTION: Despite reduction of xerostomia with intensity-modulated compared to conformal X-ray radiotherapy, radiation-induced dental complications continue to occur. Proton therapy is promising in head and neck cancers to further reduce radiation-induced side-effects, but the optimal dental management has not been defined. MATERIAL AND METHODS: Dental management before proton therapy was assessed compared to intensity-modulated radiotherapy based on a bicentric experience, a literature review and illustrative cases. RESULTS: Preserved teeth frequently contain metallic dental restorations (amalgams, crowns, implants). Metals blur CT images, introducing errors in tumour and organ contour during radiotherapy planning. Due to their physical interactions with matter, protons are more sensitive than photons to tissue composition. The composition of restorative materials is rarely documented during radiotherapy planning, introducing dose errors. Manual artefact recontouring, metal artefact-reduction CT algorithms, dual or multi-energy CT and appropriate dose calculation algorithms insufficiently compensate for contour and dose errors during proton therapy. Physical uncertainties may be associated with lower tumour control probability and more side-effects after proton therapy. Metal-induced errors should be quantified and removal of metal restorations discussed on a case by case basis between dental care specialists, radiation oncologists and physicists. Metallic amalgams can be replaced with water-equivalent materials and crowns temporarily removed depending on rehabilitation potential, dental condition and cost. Implants might contraindicate proton therapy if they are in the proton beam path. CONCLUSION: Metallic restorations may more severely affect proton than photon radiotherapy quality. Personalized dental care prior to proton therapy requires multidisciplinary assessment of metal-induced errors before choice of conservation/removal of dental metals and optimal radiotherapy.

Clinical practice in European centres treating paediatric posterior fossa tumours with pencil beam scanning proton therapy.

BACKGROUND AND PURPOSE: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing. MATERIALS AND METHODS: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared. RESULTS: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2). CONCLUSION: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.

How can we consider variable RBE and LETd prediction during clinical practice? A pediatric case report at the Normandy Proton Therapy Centre using an independent dose engine.

BACKGROUND: To develop an auxiliary GPU-accelerated proton therapy (PT) dose and LETd engine for the IBA Proteus®ONE PT system. A pediatric low-grade glioma case study is reported using FRoG during clinical practice, highlighting potential treatment planning insights using variable RBE dose (DvRBE) and LETd as indicators for clinical decision making in PT. METHODS: The physics engine for FRoG has been modified for compatibility with Proteus®ONE PT centers. Subsequently, FRoG was installed and commissioned at NPTC. Dosimetric validation was performed against measurements and the clinical TPS, RayStation (RS-MC). A head patient cohort previously treated at NPTC was collected and FRoG forward calculations were compared against RS-MC for evaluation of 3D-Γ analysis and dose volume histogram (DVH) results. Currently, treatment design at NPTC is supported with fast variable RBE and LETd calculation and is reported in a representative case for pediatric low-grade glioma. RESULTS: Simple dosimetric tests against measurements of iso-energy layers and spread-out Bragg Peaks in water verified accuracy of FRoG and RS-MC. Among the patient cohort, average 3D-Γ applying 2%/2 mm, 3%/1.5 mm and 5%/1 mm were > 97%. DVH metrics for targets and OARs between FRoG and RayStation were in good agreement, with ∆D50,CTV and ∆D2,OAR both ⪅1%. The pediatric case report demonstrated implications of different beam arrangements on DvRBE and LETd distributions. From initial planning in RayStation sharing identical optimization constraints, FRoG analysis led to plan selection of the most conservative approach, i.e., minimized DvRBE,max and LETd,max in OARs, to avoid optical system toxicity effects (i.e., vision loss). CONCLUSION: An auxiliary dose calculation system was successfully integrated into the clinical workflow at a Proteus®ONE IBA facility, in excellent agreement with measurements and RS-MC. FRoG may lead to further insight on DvRBE and LETd implications to help clinical decision making, better understand unexpected toxicities and establish novel clinical procedures with metrics currently absent from the standard clinical TPS.

Prospective Assessment of Early Proton Therapy-Induced Optic Neuropathy in Patients With Intracranial, Orbital or Sinonasal Tumors: Impact of A Standardized Ophthalmological Follow Up.

PURPOSE: Proton therapy (PT) can be a good option to achieve tumor control while reducing the probability of radiation induced toxicities compared to X-ray-based radiotherapy. However, there are still uncertainties about the effects of PT on the organs in direct contact with the irradiated volume. The aim of this prospective series was to report 6-month follow-up of clinical and functional optic neuropathy rates of patients treated by proton therapy using a standardized comprehensive optic examination. METHODS AND MATERIALS: Standardized ophthalmological examinations were performed to analyze subclinical anomalies in a systematic way before treatment and 6 months after the end of proton therapy with: Automatic visual field, Visual evoked potential (VEP) and optic coherence of tomography (OCT). RESULTS: From October 2018 to July 2020 we analyzed 81 eyes. No significant differences were found in the analysis of the clinical examination of visual functions by the radiation oncologist. However, considering VEP, the impairment was statistically significant for both fibers explored at 30'angle (p:0.007) and 60'angle (p <0.001). In patients with toxicity, the distance of the target volume from the optical pathways was more important with a p-value for 30'VEP at 0.035 and for 60'VEP at 0.039. CONCLUSIONS: These results confirm uncertainties concerning relative biological effectiveness of proton therapy, linear energy transfer appears to be more inhomogeneous especially in areas close to the target volumes. The follow-up of patients after proton therapy is not an easy process to set up but it is necessary to improve our knowledges about the biological effects of proton therapy in real life. Our study which will continue during the coming years, suggests that follow-up with in-depth examinations such as VEP as a biomarker could improve the detection of early abnormalities.

Proton therapy for head and neck squamous cell carcinomas: A review of the physical and clinical challenges.

The quality of radiation therapy has been shown to significantly influence the outcomes for head and neck squamous cell carcinoma (HNSCC) patients. The results of dosimetric studies suggest that intensity-modulated proton therapy (IMPT) could be of added value for HNSCC by being more effective than intensity-modulated (photon) radiation therapy (IMRT) for reducing side effects of radiation therapy. However, the physical properties of protons make IMPT more sensitive than photons to planning uncertainties. This could potentially have a negative effect on the quality of IMPT planning and delivery. For this review, the three French proton therapy centers collaborated to evaluate the differences between IMRT and IMPT. The review explored the effects of these uncertainties and their management for developing a robust and optimized IMPT treatment delivery plan to achieve clinical outcomes that are superior to those for IMRT. We also provide practical suggestions for the management of HNSCC carcinoma with IMPT. Because metallic dental implants can increase range uncertainties (3-10%), patient preparation for IMPT may require more systematic removal of in-field alien material than is done for IMRT. Multi-energy CT may be an alternative to calculate more accurately the dose distribution. The practical aspects that we describe are essential to guarantee optimal quality in radiation therapy in both model-based and randomized clinical trials.