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Custom intraoral radiation devices protect normal tissues, minimizing the adverse effects of radiation therapy. These devices also help immobilize the target by placing the patient's head in a precise, repeatable position. This clinical report describes the fabrication and benefits of a modified mouth opening, tongue depressing radiation stent with bilabial protrusion of the lips that was used in proton radiation therapy for a malignancy of the upper lip.

Background Compared to conventional intensity-modulated photon radiation therapy (IMRT), intensity-modulated proton radiation therapy (IMPT) has potential to reduce irradiation-induced late toxicities while maintaining excellent tumor control in patients with nasopharyngeal carcinoma (NPC). However, the relevant cost-effectiveness remains controversial. Methods A Markov decision tree analysis was performed under the assumption that IMPT offered normal tissue complication probability reduction (NTCP reduction) in long-term dysphagia, xerostomia, and hearing loss, compared to IMRT. Base-case evaluation was performed on T2N2M0 NPC of median age (43 years old). A Chinese societal willingness-to-pay threshold (33558 US dollars [$])/quality-adjusted life-year [QALY]) was adopted. Results For patients at median age and having NTCP reduction of 10%, 20%, 30%, 40%, 50%, and 60%, their incremental cost-effectiveness ratios were $102684.0/QALY, $43161.2/QALY, $24134.7/QALY, $13991.6/QALY, $8259.8/QALY, and $4436.1/QALY, respectively; IMPT should provide an NTCP reduction of ≥24% to be considered cost-effective. Conclusions IMPT has potential to be cost-effective for average Chinese NPC patients and should be validated clinically.

Head and neck squamous cell carcinomas (HNSCCs) often present as local-regionally advanced disease at diagnosis, for which a current standard of care is x-ray–based radiation therapy, with or without chemotherapy. This approach provides effective local regional tumor control, but at the cost of acute and late toxicity that can worsen quality of life and contribute to mortality. For patients with human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (SCC) in particular, for whom the prognosis is generally favorable, de-escalation of the radiation dose to surrounding normal tissues without diminishing the radiation dose to tumors is desired to mitigate radiation-related toxic effects. Proton radiation therapy (PRT) may be an excellent de-escalation strategy because of its physical properties (that eliminate unnecessary radiation to surrounding tissues) and because of its biological properties (including tumor-specific variations in relative biological effectiveness [RBE] and linear energy transfer [LET]), in combination with concurrent systemic therapy. Early clinical evidence has shown that compared with x-ray–based radiation therapy, PRT offers comparable disease control with fewer and less severe treatment-related toxicities that can worsen the quality of life for patients with HNSCC. Herein, we review aspects of the biological basis of enhanced HNSCC cell response to proton versus x-ray irradiation in terms of radiation-induced gene and protein expression, DNA damage and repair, cell death, tumor immune responses, and radiosensitization of tumors.

Purpose In value-based health care delivery, radiation oncologists need to compare empiric costs of care delivery with advanced technologies, such as intensity-modulated proton therapy (IMPT) and intensity-modulated radiation therapy (IMRT). We used time-driven activity-based costing (TDABC) to compare the costs of delivering IMPT and IMRT in a case-matched pilot study of patients with newly diagnosed oropharyngeal (OPC) cancer. Materials and Methods We used clinicopathologic factors to match 25 patients with OPC who received IMPT in 2011-12 with 25 patients with OPC treated with IMRT in 2000-09. Process maps were created for each multidisciplinary clinical activity (including chemotherapy and ancillary services) from initial consultation through 1 month of follow-up. Resource costs and times were determined for each activity. Each patient-specific activity was linked with a process map and TDABC over the full cycle of care. All calculated costs were normalized to the lowest-cost IMRT patient. Results TDABC costs for IMRT were 1.00 to 3.33 times that of the lowest-cost IMRT patient (mean ± SD: 1.65 ± 0.56), while costs for IMPT were 1.88 to 4.32 times that of the lowest-cost IMRT patient (2.58 ± 0.39) (P Conclusions In this matched sample, although IMPT was on average more costly than IMRT primarily owing to higher equipment costs, a subset of IMRT patients had similar costs to IMPT patients, owing to greater use of supportive care resources. Multidimensional patient outcomes and TDABC provide vital methodology for defining the value of radiation therapy modalities.

A variant of the proton beam delivery system with an energy of 60 MeV for the future oncological ophthalmological center for proton radiation therapy at the isochronous cyclotron C-80 at PNPI was designed. The requirements to the beam characteristics were defined. On the basis of a series of calculations, the optimal parameters and composition of the beam line elements were determined. It is shown that such a beam line allows one to alternately and efficiently switch from the isotope production mode on the cyclotron to the mode of operation of the center for proton radiation therapy without fundamental overhaul of the accelerator systems.

This paper presents an insight into the critical discussions and the current strategies of the Nordic countries for handling the variable proton relative biological effectiveness (RBE) as presented at The Nordic Collaborative Workshop for Particle Therapy that took place at the Skandion Clinic on 14th and 15th of November 2019.In the current clinical practice at the two proton centres in operation at the date, Skandion Clinic, and the Danish Centre for Particle Therapy, a constant proton RBE of 1.1 is applied. The potentially increased effectiveness at the end of the particle range is however considered at the stage of treatment planning at both places based on empirical observations and knowledge. More elaborated strategies to evaluate the plans and mitigate the problem are intensely investigated internationally as well at the two centres. They involve the calculation of the dose-averaged linear energy transfer (LETMethods and tools for LETThe need for collaboration between the clinical proton centres in establishing common platforms and perspectives for treatment planning evaluation and optimisation is highlighted as well as the need of close interaction with the research academic groups that could offer a complementary perspective and actively help developing methods and tools for clinical implementation of the more complex metrics for considering the variable effectiveness of the proton beams.

The aim of this study is to compare the effectiveness of carbon ion radiation therapy (CIRT), proton radiation therapy (PRT), and photon‐based intensity‐modulated radiation therapy (IMRT) in the treatment of sinonasal malignancies. We identified studies through systematic review and divided them into three cohorts (CIRT group/PRT group/IMRT group). Primary outcomes of interest were overall survival (OS) and local control (LC). We pooled the outcomes with meta‐analysis and compared the survival difference among groups using Chi2 (χ 2) test. A representative sample of 2282 patients with sinonasal malignancies (911 in the CIRT group, 599 in the PRT group, and 772 in the IMRT group) from 44 observation studies (7 CIRT, 16 PRT, and 21 IMRT) was included. The pooled 3‐year OS, LC, distant metastasis–free survival, and progression‐free survival rates were 67.0%, 72.8%, 69.4%, and 52.8%, respectively. Through cross‐group analysis, the OS was significantly higher after CIRT (75.1%, 95% CI: 67.1%‐83.2%) than PRT (66.2%, 95% CI: 57.7%‐74.6%; χ 2 = 13.374, P, Carbon‐ion radiation therapy achieved higher overall survival and local control rates as compared to both proton radiation therapy and photon based intensity‐modulated radiation therapy through meta‐analysis of 2, 282 patients with sinonasal malignancies from the real world. CIRT appeared to provide better OS and LC for patients with malignancies of nasal cavity and paranasal sinuses.

Purpose To evaluate why small- and certain medium-sized parapapillary choroidal melanoma (pcM) patients treated with hypo-fractionated proton therapy (PT) retain excellent long-term visual acuity (VA) and assess the negative predictive factors for retaining good vision (≤ 0.2 logMAR (≥ 0.6 decimal) after 5 years. Methods This single-center, retrospective, comparative study recruited consecutive pcM patients that were treated with PT. Between 1984 and 2005, 609 patients received a total of 60 CGE, of whom 310 met the following inclusion criteria: posterior tumor border ≤ 2.5 mm from the optic disc, largest tumor diameter ≤ 17.9 mm, tumor thickness ≤ 5.2 mm and available follow-up data for at least 5 years. Results Mean follow-up was 120.8 ± 48.8 months (54.0–295.0). Out of 310 patients, 64 (21%) maintained a VA ≤ 0.2 logMAR (≥ 0.6 decimal) for at least 5 years following PT and were allocated to the “good visual outcome” (GVO) group, while the remaining 246 (79%) constituted the “poor visual outcome” (PVO) group, subdivided into 70 (22%) with a VA of 0.3–1.0 logMAR (0.1–0.5 decimal) and 157 (57%) patients with a VA > 1.0 logMAR (P = 0.04), tumor localization ≤ 0.5 mm to the fovea (P P = 0.02 and P Conclusions Of 310 small- to medium-sized pcM patients successfully treated with PT, 21% retained a VA ≤ 0.2 logMAR (≥ 0.6 decimal) for at least 5 years. Strongest negative predictive factor for retaining good long-term vision was the volume of the macula irradiated with at least 30 Gy.

The article presents two opinions regarding proton radiation therapy, its physical basis, dosimetric specifics and clinical efficacy in comparison with more traditional photon irradiation, as well as the authors» opinions concerning the expanding indications for proton therapy and the rationale for opening new centers for proton treatment in the world. This review has become a continuation of the discussion session on proton therapy held at the XXIII Russian Oncology Congress in November 2019.

INTRODUCTION Our group previously demonstrated stability in neurocognitive function (NCF) over a 5-year period after proton radiation therapy (PRT) in low grade glioma (LGG) patients. Subjective cognitive function (SCF) had not been previously explored, nor had individual analyses of cognition, which can detect variability in trajectory. We used the newly derived Functional Assessment of Cancer Therapy-Brain Cognitive-Index (FACT-Br-CI) to examine SCF in LGG patients after PRT and compare longitudinal changes in SCF and NCF. METHODS 20 LGG patients (M age =37.5) treated with PRT completed NCF tests and self-report measures annually for 5 years or until tumor progression. Group change in SCF was examined with paired t-test (baseline vs final FACT-Br-CI). Individual change scores were calculated for FACT-Br-CI and NCF tests (clinical trials battery composite; CTBC). Individual deterioration in NCF was defined by reliable change index (RCI) on CTBC, and in SCF was defined as decline of >/=1 SD in FACT-Br-CI. Relationships between change in SCF and NCF were explored with correlations. RESULTS At the group level, no change was observed in FACT-Br-CI between baseline and last follow-up (t(19)=-.91;p=ns). Individual SCF analyses at last follow-up found the number of patients reporting decline=3 (15%), improvement=5 (25%), and no change=12 (60%). Individual changes were observed in SCF in 20% of patients at 3 months, 5.9% at 6 months, 12.5% at 12 months, 13.3% at 24 months, and 11.1% at 36 months. Median time to any deterioration in SCF was 36 months and for NCF was not reached. Correlation between CTBC and FACT-Br-CI change scores did not reach statistical significance (r=.41;p=ns). CONCLUSION Consistent with previous research, group analyses of LGG patients did not show cognitive decline after PRT. However individual analyses of SCF showed variability within the group: some patients experienced cognitive decline during follow up. Consideration of individual differences may yield additional information.

Background Treatment of intracranial arteriovenous malformations (AVMs) includes surgery, radiation therapy, endovascular occlusion, or a combination. Proton radiation therapy enables very focused radiation, minimizing dose to the surrounding brain. Purpose To evaluate the presence of radiation-induced changes on post-treatment MRI in patients with AVMs treated with proton radiation and to compare these with development of symptoms and nidus obliteration. Material and Methods Retrospective review of pre- and post-treatment digital subtraction angiography and MRI and medical records in 30 patients with AVMs treated with proton radiation. Patients were treated with two or five fractions; total radiation dose was 20–35 physical Gy. Vasogenic edema (minimal, perinidal, or severe), contrast enhancement (minimal or annular), cavitation and nidus obliteration (total, partial, or none) were assessed. Results 26 of 30 patients (87%) developed MRI changes. Vasogenic edema was seen in 25 of 30 (83%), abnormal contrast enhancement in 18 of 26 (69%) and cavitation in 5 of 30 (17%). Time from treatment to appearance of MRI changes varied between 5 and 25 months (median 7, mean 10). Seven patients developed new or deteriorating symptoms that required treatment with corticosteroids; all these patients had extensive MRI changes (severe vasogenic edema and annular contrast enhancement). Not all patients with extensive MRI changes developed symptoms. We found no relation between MRI changes and nidus obliteration. Conclusion Radiation-induced MRI changes are seen in a majority of patients after proton radiation treatment of AVMs. Extensive MRI changes are associated with new or deteriorating symptoms.

Background: Pediatric brain tumor survivors are at risk for poor social outcomes. It remains unknown whether cognitive sparing with proton radiotherapy (PRT) supports better social outcomes relative to photon radiotherapy (XRT). We hypothesized that survivors treated with PRT would outperform those treated with XRT on measures of cognitive and social outcomes. Further, we hypothesized that cognitive performance would predict survivor social outcomes. Procedure: Survivors who underwent PRT (n=38) or XRT (n=20) participated in a neurocognitive evaluation >1 year post-radiotherapy. Group differences in cognitive and social functioning were assessed using ANCOVA. Regression analyses examined predictors of peer relations and social skills. Results: Age at evaluation, radiation dose, tumor diameter, and sex did not differ between groups (all p>0.05). However, XRT participants were younger at diagnosis (XRT M=5.0 years, PRT M=7.6 years) and further out from radiotherapy (XRT M=8.7 years, PRT M=4.6 years). The XRT group performed worse than the PRT group on measures of processing speed (p=0.01) and verbal memory (p

Purpose One significant advantage of proton therapy is its ability to improve normal tissue sparing and toxicity mitigation, which is relevant in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). Here, we report our institutional experience and dosimetric results with adjuvant proton radiation therapy (PRT) versus intensity-modulated radiotherapy (IMRT) for Human Papilloma Virus (HPV)-associated OPSCC. Materials and Methods This was a retrospective, single institutional study of all patients treated with adjuvant PRT for HPV-associated OPSCC from 2015 to 2019. Each patient had a treatment-approved equivalent IMRT plan to serve as a reference. Endpoints included dosimetric outcomes to the organs at risk (OARs), local regional control (LRC), progression-free survival (PFS), and overall survival (OS). Descriptive statistics, a 2-tailed paired t test for dosimetric comparisons, and the Kaplan-Meier method for disease outcomes were used. Results Fifty-three patients were identified. Doses delivered to OARs compared favorably for PRT versus IMRT, particularly for the pharyngeal constrictors, esophagus, larynx, oral cavity, and submandibular and parotid glands. The achieved normal tissue sparing did not negatively impact disease outcomes, with 2-year LRC, PFS, and OS of 97.0%, 90.3%, and 97.5%, respectively. Conclusion Our study suggests that meaningful normal tissue sparing in the postoperative setting is achievable with PRT, without impacting disease outcomes.

The treatment of cancer with proton radiation therapy was first suggested in 1946 followed by the first treatments in the 1950s. As of 2020, almost 200 000 patients have been treated with proton beams worldwide and the number of operating proton therapy (PT) facilities will soon reach one hundred. PT has long moved from research institutions into hospital-based facilities that are increasingly being utilized with workflows similar to conventional radiation therapy. While PT has become mainstream and has established itself as a treatment option for many cancers, it is still an area of active research for various reasons: the advanced dose shaping capabilities of PT cause susceptibility to uncertainties, the high degrees of freedom in dose delivery offer room for further improvements, the limited experience and understanding of optimizing pencil beam scanning, and the biological effect difference compared to photon radiation. In addition to these challenges and opportunities currently being investigated, there is an economic aspect because PT treatments are, on average, still more expensive compared to conventional photon based treatment options. This roadmap highlights the current state and future direction in PT categorized into four different themes, ‘improving efficiency’, ‘improving planning and delivery’, ‘improving imaging’, and ‘improving patient selection’.

MRI-only treatment planning is highly desirable in the current proton radiation therapy workflow due to its appealing advantages such as bypassing MR-CT co-registration, avoiding x-ray CT exposure dose and reduced medical cost. However, MRI alone cannot provide stopping power ratio (SPR) information for dose calculations. Given that dual energy CT (DECT) can estimate SPR with higher accuracy than conventional single energy CT, we propose a deep learning-based method in this study to generate synthetic DECT (sDECT) from MRI to calculate SPR. Since the contrast difference between high-energy and low-energy CT (LECT) is important, and in order to accurately model this difference, we propose a novel label generative adversarial network-based model which can not only discriminate the realism of sDECT but also differentiate high-energy CT (HECT) and LECT from DECT. A cohort of 57 head-and-neck cancer patients with DECT and MRI pairs were used to validate the performance of the proposed framework. The results of sDECT and its derived SPR maps were compared with clinical DECT and the corresponding SPR, respectively. The mean absolute error for synthetic LECT and HECT were 79.98 ± 18.11 HU and 80.15 ± 16.27 HU, respectively. The corresponding SPR maps generated from sDECT showed a normalized mean absolute error as 5.22% ± 1.23%. By comparing with the traditional Cycle GANs, our proposed method significantly improves the accuracy of sDECT. The results indicate that on our dataset, the sDECT image form MRI is close to planning DECT, and thus shows promising potential for generating SPR maps for proton therapy.

Протонная терапия используется для лечения Ð¼Ð½Ð¾Ð³Ð¸Ñ Ð²Ð¸Ð´Ð¾Ð² Ð·Ð»Ð¾ÐºÐ°Ñ‡ÐµÑÑ‚Ð²ÐµÐ½Ð½Ñ‹Ñ Ð¾Ð¿ÑƒÑ Ð¾Ð»ÐµÐ¹. Благодаря уникальным свойствам пучком протонов облучают труднодоступные для Ñ Ð¸Ñ€ÑƒÑ€Ð³Ð¸Ñ‡ÐµÑÐºÐ¾Ð³Ð¾ вмешательства Ð¾Ð¿ÑƒÑ Ð¾Ð»Ð¸. Однако есть трудности в широком применении протонной терапии. Значительно увеличить эффективность методов лучевой терапии может применение радиосенсибилизаторов. Некоторые препараты, содержащие 10В уже используется в качестве радиосенсибилизаторов в бор-нейтрон-Ð·Ð°Ñ Ð²Ð°Ñ‚Ð½Ð¾Ð¹ терапии. Было предложено использовать эти же препараты в протонной терапии за счет ядерной реакции протонов на изотопе 11B с образованием α-частиц для увеличения поглощенной дозы в Ð¾Ð¿ÑƒÑ Ð¾Ð»ÐµÐ²Ð¾Ð¹ мишени. Данная исследовательская работа направлена на изучение сенсибилизирующего потенциала соединений 11B (Na2B4O7; Na2B12H11SH) при облучении протонами на пике Брэгга ÐºÑƒÐ»ÑŒÑ‚Ð¸Ð²Ð¸Ñ€ÑƒÐµÐ¼Ñ‹Ñ Ð·Ð»Ð¾ÐºÐ°Ñ‡ÐµÑÑ‚Ð²ÐµÐ½Ð½Ñ‹Ñ ÐºÐ»ÐµÑ‚Ð¾Ðº. Три клеточные линии предварительно инкубировали с соединением 11B и облучали дозами 0-8 Гр протонами на пике Брэгга, а также гамма-лучами. Для тетрабората натрия (Na2B4O7) доказана радиосенсибилизирующая активность, однако связанная не с физической реакцией, а с биологическими эффектами, оказываемыми препаратом. Для боркаптата натрия (Na2B12H11SH) доказано отсутствие радиосенсибилизирующего эффекта. Полученные данные говорят о том, что 11B не является радиосенсибилизатором при облучении Ð·Ð»Ð¾ÐºÐ°Ñ‡ÐµÑÑ‚Ð²ÐµÐ½Ð½Ñ‹Ñ ÐºÐ»ÐµÑ‚Ð¾Ðº человека протонами на пике Брэгга по Ð¼ÐµÑ Ð°Ð½Ð¸Ð·Ð¼Ñƒ ядерной реакции 11B + p → 3α., Proton therapy is used to treat many types of cancer. Due to proton’s unique properties, the tumors that are difficult to reach for surgical procedures could be irradiated by the proton beam. However, there are certain difficulties in the widespread use of proton therapy. The use of radiosensitizers can significantly increase the effectiveness of radiation therapy methods. Boron is already used as a radiosensitizer in boron neutron capture therapy. It was suggested that the same drugs could be used in proton therapy due to the nuclear reaction of protons on the isotope 11B with the formation of α-particles to increase the absorbed dose in the tumor target. The given work is devoted to the identification of the radiosensitizing properties of boron compounds on cancerous cells irradiated at the proton Bragg peak. Two human gliomas and one adenocarcinoma were pre-incubated with the boron compound (Na2B4O7, Na2B12H11SH) and irradiated with doses 0-8 Gy at the proton Bragg peak and gamma rays. The radiosensitizing activity was proved for one of the compounds (that turned out to be toxic), but it is not associated with a physical reaction, but with biological effects. The absence of a radiosensitizing effect was proved for the other compound. The data suggest that boron is not a radiosensitizer in proton therapy.

The Monte Carlo method was employed to simulate realistic treatment situations for photon and proton radiation therapy for a set of Oak Ridge National Laboratory (ORNL) pediatric phantoms for 15, 10, 5 and 1-year olds as well as newborns. Complete radiotherapy situations were simulated using the previously developed NRUrad input code for Monte Carlo N-Particle (MCNP) code package. Each pediatric phantom was irradiated at five different positions, namely, the testes, colon, liver, left lung and brain, and the doses in targeted organs (Dt) were determined using the track length estimate of energy. The dispersed photon and proton doses in non-targeted organs (Dd), namely, the skeleton, skin, brain, spine, left and right lungs were computed. The conversion coefficients (F = Dd/Dt) of the dispersed doses were used to study the dose dispersion in different non-targeted organs for phantoms for 15, 10, 5 and 1-year olds as well as newborns. In general, the F values were larger for younger patients. The F values for non-targeted organs for phantoms for 1-year olds and newborns were significantly larger compared to those for other phantoms. The dispersed doses from proton radiation therapy were also found to be significantly lower than those from conventional photon radiation therapy. For example, the largest F values for the brain were 65.6% and 0.206% of the dose delivered to the left lung (P4) for newborns during photon and proton radiation therapy, respectively. The present results demonstrated that dispersion of photons and generated electrons significantly affected the absorbed doses in non-targeted organs during pediatric photon therapy, and illustrated that proton therapy could in general bring benefits for treatment of pediatric cancer patients.

Background Proton beam therapy (PBT) is a new-emerging cancer treatment in China but its treatment costs are high and not yet covered by Chinese public medical insurance. The advanced form of PBT, intensity-modulated proton radiation therapy (IMPT), has been confirmed to reduce normal tissue complication probability (NTCP) as compared to conventional intensity-modulated photon-radiation therapy (IMRT) in patients with oropharyngeal cancer (OPC). Herein, we evaluated the cost-effectiveness and applicability of IMPT versus IMRT for OPC patients in China, aiming at guiding the proper use of PBT. Methods A 7-state Markov model was designed for analysis. Base-case evaluation was performed on a 56-year-old (median age of OPC in China) patient under the assumption that IMPT could provide a 25% NTCP-reduction in long-term symptomatic dysphagia and xerostomia. Model robustness was examined using probabilistic sensitivity analysis, cohort analysis, and tornado diagram. One-way sensitivity analyses were conducted to identify the cost-effective scenarios. IMPT was considered as cost-effective if the incremental cost-effectiveness ratio (ICER) was below the societal willingness-to-pay (WTP) threshold. Results Compared with IMRT, IMPT provided an extra 0.205 quality-adjusted life-year (QALY) at an additional cost of 34,926.6 US dollars ($), and had an ICER of $170,082.4/ QALY for the base case. At the current WTP of China ($33,558 / QALY) and a current IMPT treatment costs of $50,000, IMPT should provide a minimum NTCP-reduction of 47.5, 50.8, 55.6, 63.3 and 77.2% to be considered cost-effective for patient age levels of 10, 20, 30, 40 and 50-year-old, respectively. For patients at the median age level, reducing the current IMPT costs ($50,000) to a $30,000 level would make the minimum NTCP-reduction threshold for “cost-effective” decrease from 91.4 to 44.6%, at the current WTP of China (from 69.0 to 33.5%, at a WTP of $50,000 / QALY; and from 39.7 to 19.1%, at a WTP of $100,000 / QALY). Conclusions Cost-effective scenarios of PBT exist in Chinese OPC patients at the current WTP of China. Considering a potential upcoming increase in PBT use in China, such cost-effective scenarios may further expand if a decrease of proton treatment costs occurs or an increase of WTP level.

Background: To report the clinical experience of carbon-ion and proton radiation therapy for skull base sarcomas. Methods: An analysis of the retrospective data registry from the Shanghai Proton and Heavy Ion Center for patients with skull base sarcomas was conducted. The 1-/2-year local relapse-free, distant metastasis-free, progression-free, and overall survival (LRFS, DMFS, PFS, OS) rates as well as associated prognostic indicators were analyzed. Radiotherapy-induced acute and late toxicities were summarized. Results: Between 7/2014 and 5/2019, 62 patients with skull base sarcomas of various subtypes received carbon-ion radiation therapy (53), proton radiation therapy (5), or proton radiation therapy + carbon-ion boost (4). With a median follow-up of 20.4 (range 2.73-91.67) months, the 1-/2-year OS, LRFS, DMFS, and PFS rates were 91.2%/80.2%, 89.2%/80.2%, 86.0%/81.1%, and 75.8%/62.9%, respectively. Grade 3 mucositis and grade 4 hemorrhage were observed in 1 patient for each. Only grade 1 and grade 2 toxicities were observed except for the same patient with grade 4 acute toxicity died of severe hemorrhage (grade 5). Multivariate analyses revealed the lack of prior RT was an independent favorable prognostic factor for OS, PFS, and LRFS, age under 40 was associated with improved OS, early T-disease (T1/2) showed a significant association with better PFS. Conclusion: With few observed acute and late toxicities, particle beam radiation therapy provided effective tumor control and overall survival for patients with skull base sarcomas.

In terms of dose distribution, protons are more sensitive to range variations than photons due to their unique properties. The aim of this study was to develop a method to identify patient-specific robust proton beam angles for lung tumor irradiation by investigating the association between water equivalent thickness (WET) variation and inter-fraction motion-induced target dose degradation. Using 3-dimensional computed tomography (3D-CT) images, the impact of WET variations on the target dose coverage of a series of coplanar proton beams was evaluated for 4 patients with lung cancer. Using ray tracing, WET maps, or WET baseline, were estimated for the internal target volume (ITV) at every 5° gantry interval in the axial plane. After calculating the WET baseline, the planning CT was shifted 5 mm in each anterior-posterior (AP), superior-inferior (SI), and left-right (LR) direction, yielding a total of 6 shifted CTs, and differential WET maps between the planning CT and each shifted CT were calculated. Target dose differences were associated with the average WET change between the original planning CT and the shifted CTs for all 360° gantry rotation beams. Target and OAR dose metrics in the ΔWET-guided plans were compared with those of the clinical plans. The WET variation maps showed areas of both high and low WET variations, with overall similar patterns yet individual differences reflecting tumor position differences. For all 4 patients investigated in this study, the coplanar plans demonstrated a strong correlation between WET changes and ITV dose reductions. Target dose coverage was more stable with the ΔWET-guided plan while OAR doses were comparable to the clinical plan. The WET variation maps have been used in this pilot study to identify proton beam angles that are either sensitive or robust to WET changes in proton passive scattering. This work demonstrates the feasibility of using WET variation maps to assist the planner in inter-fraction motion-robust proton beam angle selection.

Introduction The intracranial skull-base meningioma is in proximity to multiple critical organs and heterogeneous tissues. Steep dose gradients often result from avoiding critical organs in proton treatment plans. Dose uncertainties arising from setup errors under image-guided radiation therapy are worthy of evaluation. Patients and Methods Fourteen patients with skull-base meningioma were retrospectively identified and planned with proton pencil beam scanning (PBS) single-field uniform dose (SFUD) and multifield optimization (MFO) techniques. The setup uncertainties were assigned a probability model on the basis of prior published data. The impact on the dose distribution from nominal 1-mm and large, less probable setup errors, as well as the cumulative effect, was analyzed. The robustness of SFUD and MFO planning techniques in these scenarios was discussed. Results The target coverage was reduced and the plan dose hot spot increased by all setup uncertainty scenarios regardless of the planning techniques. For 1 mm nominal shifts, the deviations in clinical target volume (CTV) coverage D99% was −11 ± 52 cGy and −45 ± 147 cGy for SFUD and MFO plans. The setup uncertainties affected the organ at risk (OAR) dose both positively and negatively. The statistical average of the setup uncertainties had Conclusion It is important to understand the impact of setup uncertainties on skull-base meningioma, as the tumor target has complex shape and is in proximity to multiple critical organs. Our work evaluated the setup uncertainty based on its probability distribution and evaluated the dosimetric consequences. In general, the SFUD plans demonstrated more robustness than the MFO plans in target coverages and brainstem dose. The probability-weighted overall effect on the dose distribution is small compared to the dosimetric shift during single fraction.

Aim/objectives/background The American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for proton beam radiation therapy. Proton radiotherapy is the application of a high-energy proton beam to a patient in a clinical setting with therapeutic intent. Proton radiotherapy may permit improved therapeutic ratios with lower doses to sensitive normal structures and greater dose to target tumor tissues. Methods A literature search was performed to identify published articles regarding clinical outcomes, reviews, quality assurance methodologies, and guidelines and standards for proton radiation therapy. Selected articles are referenced in the text. The following recommendations are based on firsthand experiences of multiple clinical authorities who employ proton therapy and have been peer reviewed by experts at different practicing institutions. Results This practice parameter is developed to serve as a tool in the appropriate application of this evolving technology in the care of cancer patients or other patients with conditions where radiation therapy is indicated. It addresses clinical implementation of proton radiation therapy, including personnel qualifications, quality assurance standards, indications, and suggested documentation. Conclusions This practice parameter is a tool to guide technical use of proton therapy and does not assess the relative clinical indication of proton radiotherapy when compared with other forms of radiotherapy, but to focus on the best practices required to deliver proton therapy safely and effectively, when clinically indicated. Costs of proton treatments are high, and the economic costs of proton radiotherapy may also need to be considered.

Purpose Proton beam radiation therapy (PBT) has been increasingly used to treat pediatric brain tumors; however, limited information exists regarding radiation-induced cerebral microbleeds (CMBs) among these patients. The purpose of this study was to evaluate the incidence, risk factors, and imaging appearance of CMBs in pediatric patients with brain tumors treated with PBT. Materials and Methods A retrospective study was performed of 100 pediatric patients with primary brain tumors treated with PBT. CMBs were diagnosed by examination of serial magnetic resonance imaging scans, including susceptibility-weighted imaging. Radiation therapy plans were analyzed to determine doses to individual CMBs. Clinical records were used to determine risk factors associated with the development of CMBs in these patients. Results The mean age at time of PBT was 8.1 years. The median follow-up duration was 57 months. The median time to development of CMBs was 8 months (mean, 11 months; range, 3-28 months). The percentage of patients with CMBs was 43%, 66%, 80%, 81%, 83%, and 81% at 1 year, 2 years, 3 years, 4 years, 5 years, and >5 years from completion of proton radiation therapy. Most of the CMBs (87%) were found in areas of brain exposed to ≥30 Gy. Risk factors included maximum radiation therapy dose (P = .001), percentage and volume of brain exposed to ≥30 Gy (P = .0004, P = .0005), and patient age at time of PBT (P = .0004). Chemotherapy was not a significant risk factor (P = .35). No CMBs required surgical intervention. Conclusions CMBs develop in a high percentage of pediatric patients with brain tumors treated with proton radiation therapy within the first few years after treatment. Significant risk factors for development of CMBs include younger age at time of PBT, higher maximum radiation therapy dose, and higher percentage and volume of brain exposed to ≥30 Gy. These findings demonstrate similarities with CMBs that develop in pediatric patients with brain tumor treated with photon radiation therapy.

Purpose: To examine national care patterns in proton radiation therapy (PBT) use for non–small cell lung cancer (NSCLC) and the effect of facility type on survival. Patients and Methods: Using the National Cancer Database, we identified 506 patients with a diagnosis of NSCLC from 2004-2014 who underwent PBT. Patients were categorized as having received treatment at an academic/research facility (ARF) or a form of community cancer program (CCP). Descriptive analysis was performed, and overall survival was analyzed by Kaplan-Meier methods and Cox proportional hazard models. Results: Treatments at ARFs and CCPs were equally distributed with 253 patients at each facility type. A positive trend in PBT use over time was observed with 2.8% of cases being treated in 2008 compared to 21.5% in 2014 (P = .001). Definitive doses (≥60 Gy) were more commonly given at ARFs than CCPs (72% versus 45%, respectively; P

Background Propofol is an excellent hypnotic drug for use in repeated radiation procedures in young children. To date, tolerance to propofol generally does not develop in pediatric patients undergoing radiation therapy. However, several studies have suggested that there may be potential for development of tolerance to propofol. The aim of this study was to evaluate the development of a tolerance to propofol used for repeated deep sedation in children undergoing proton radiation therapy (PRT). Methods All children undergoing PRT at our institution between December 2015 and January 2018 were eligible for inclusion in this study. Sedation was induced by a bolus dose of propofol (2.0 mg.kg− 1) followed by a continuous infusion of 250 μg.kg− 1.min− 1 via an infusion pump to achieve deep sedation. Sedation was maintained with the propofol infusion of 200 μg.kg− 1.min− 1, which was adjusted in 25 μg.kg− 1.min− 1 increments up or down as necessary to ensure deep sedation. The primary outcome was mean doses of propofol over time. Results Fifty-eight children were analyzed. The mean (SD) age was 4.5 (2.1) years. The mean (SD) number of treatment sessions was 19 (7). Fifteen patients (26%) developed tolerance to propofol. However, there were no significant differences between the children who developed tolerance and the children who did not develop tolerance in mean propofol dose and awakening time over time (p = 0.887 and P = 0.652, respectively). Age, the number of PRT, and attending anesthesiologists was not significantly associated with the incidence of tolerance to propofol. Conclusion Repeated prolonged deep sedation for PRT elicited multiple times over several weeks in young children using propofol did not develop tolerance in 74% of patients. Although the incidence of 26% tolerance to propofol may still be present, the increase in propofol dose was minimal. Therefore, the use of repeated propofol for children was safe.

Proton radiotherapy confers significant dosimetric advantages in the treatment of malignancies that arise adjacent to critical radiosensitive structures. To date, these advantages have been most prominent in the treatment of pediatric and central nervous system malignancies, although emerging data support the use of protons among other anatomical sites in which radiotherapy plays an important role. With advances in the overall treatment paradigm for breast cancer, most patients with localized disease now exhibit long-term disease control and, consequently, may manifest the late toxicities of aggressive treatment. As a result, there is increasing emphasis on the mitigation of iatrogenic morbidity, with particular attention to heart and lung exposure in those receiving adjuvant radiotherapy. Indeed, recent landmark analyses have demonstrated an increase in significant cardiac events that is linked directly to low-dose radiation to the heart. Coupled with practice-changing trials that have expanded the indications for comprehensive regional nodal irradiation, there exists significant interest in employing novel technologies to mitigate cardiac dose while improving target volume coverage. Proton radiotherapy enjoys distinct physical advantages over photon-based approaches and, in appropriately selected patients, markedly improves both target coverage and normal tissue sparing. Here, we review the dosimetric evidence that underlies the putative benefits of proton radiotherapy, and further synthesize early clinical evidence that supports the efficacy and feasibility of proton radiation in breast cancer. Landmark, prospective randomized trials are underway and will ultimately define the role for protons in the treatment of this disease.

Lung cancer, due to its poor clinical outcomes and significant toxicity associated with standard photon-based radiation, is a disease site that has the potential to greatly benefit from accurate treatment with proton radiation therapy. The potential of proton therapy is the ability to increase the radiation dose to the tumor while simultaneously decreasing the radiation dose to surrounding healthy tissues. For lung cancer treatment, this could mean significant sparing of the uninvolved healthy lung, which is difficult to achieve with external photon beam therapy, or decreasing the heart dose. In treating lung cancer with proton therapy, some additional considerations need to be made compared to treating patients with external photon beam radiation therapy. These include accounting for the finite range of protons in the patient, understanding temporal effects, potential dose discrepancies and choosing an appropriate treatment planning system for the task. One final consideration is differences between the different available proton therapy delivery systems-passive scattered proton therapy (PSPT) and active scanning proton therapy.

In recent years there has been increasing interest in the more extensive application of proton therapy in a clinical and preferably hospital-based environment. However, broader adoption of proton therapy has been hindered by the costs of treatment, which are still much higher than those in advanced photon therapy. This article presents an overview of on-going technical developments, which have a reduction of the capital investment or operational costs either as a major goal or as a potential outcome. Developments in instrumentation for proton therapy, such as gantries and accelerators, as well as facility layout and efficiency in treatment logistics will be discussed in this context. Some of these developments are indeed expected to reduce the costs. The examples will show, however, that a dramatic cost reduction of proton therapy is not expected in the near future. Although current developments will certainly contribute to a gradual decrease of the treatment costs in the coming years, many steps will still have to be made to achieve a much lower cost per treatment.

Purpose We present and evaluate a fully automated 2D-3D intensity-based registration framework using a single limited field-of-view (FOV) 2D kV radiograph and a 3D kV CBCT for 3D estimation of patient setup errors during brain radiotherapy. Methods We evaluated two similarity measures, the Pearson correlation coefficient on image intensity values (ICC) and maximum likelihood measure with Gaussian noise (MLG), derived from the statistics of transmission images. Pose determination experiments were conducted on 2D kV radiographs in the anterior-posterior (AP) and left lateral (LL) views and 3D kV CBCTs of an anthropomorphic head phantom. In order to minimize radiation exposure and exclude nonrigid structures from the registration, limited FOV 2D kV radiographs were employed. A spatial frequency band useful for the 2D-3D registration was identified from the bone-to-no-bone spectral ratio (BNBSR) of digitally reconstructed radiographs (DRRs) computed from the 3D kV planning CT of the phantom. The images being registered were filtered accordingly prior to computation of the similarity measures. We evaluated the registration accuracy achievable with a single 2D kV radiograph and with the registration results from the AP and LL views combined. We also compared the performance of the 2D-3D registration solutions proposed to that of a commercial 3D-3D registration algorithm, which used the entire skull for the registration. The ground truth was determined from markers affixed to the phantom and visible in the CBCT images. Results The accuracy of the 2D-3D registration solutions, as quantified by the root mean squared value of the target registration error (TRE) calculated over a radius of 3 cm for all poses tested, was ICCAP : 0.56 mm, MLGAP : 0.74 mm, ICCLL : 0.57 mm, MLGLL : 0.54 mm, ICC (AP and LL combined): 0.19 mm, and MLG (AP and LL combined): 0.21 mm. The accuracy of the 3D-3D registration algorithm was 0.27 mm. There was no significant difference in mean TRE for the 2D-3D registration algorithms using a single 2D kV radiograph with similarity measure and image view point. There was no significant difference in mean TRE between ICCLL , MLGLL , ICC (AP and LL combined), MLG (AP and LL combined), and the 3D-3D registration algorithm despite the smaller FOV used for the 2D-3D registration. While submillimeter registration accuracy was obtained with both ICC and MLG using a single 2D kV radiograph, combining the results from the two projection views resulted in a significantly smaller (P≤0.05) mean TRE. Conclusions Our results indicate that it is possible to achieve submillimeter registration accuracy with both ICC and MLG using either single or dual limited FOV 2D kV radiographs of the head in the AP and LL views. The registration accuracy suggests that the 2D-3D registration solutions presented are suitable for the estimation of patient setup errors not only during conventional brain radiation therapy, but also during stereotactic procedures and proton radiation therapy where tighter setup margins are required.

Background: Integrated proton therapy - MRI systems are capable of delivering high doses to the target tissues near sensitive organs and achieve better therapeutic results; however, the applied magnetic field for imaging, influences the protons path, changes the penetration depth and deflects the particles, laterally, leading to dose distribution variations. Objective: To determine the effects of a magnetic field on the range and the lateral deflection of protons, analytically. Methods: An analytical survey based on protons energy and range power law relation, without using small angle assumption was done. The penetration depth and lateral deflection of protons with therapeutic energy ranges 60- 250 MeV in the presence of uniform magnetic fields of 0-10T intensities, were calculated analytically. Calculations were done for relativistic conditions with Mathematica software version 7.0, and MATLAB 7.0 was applied to plot curves and curve fittings. Results: In the presence of a magnetic field, the depth of Bragg peak was decreased and it was shifted laterally. A second order polynomial model with power equation for its coefficients and a power model with quadratic polynomial coefficients predicted the maximum lateral deflection (ymax) and maximum penetration depth (zmax) variations with energy and magnetic field intensity, respectively. Conclusion: The applied correction for deflection angle will give more reliable results in initial energy of 250 MeV and 3T magnetic field intensity. For lower energies and magnetic field intensities the differences are negligible, clinically

Proton radiation therapy needs to be further developed in Poland by virtue of both epidemiological considerations and because this type of radiation exhibits very advantageous biological and physical properties. The underlying benefit of such therapy is to make lower integral radiation dose delivered to structures beyond a given target area, including critical organs, resulting in reduced toxicities for patients. Of somewhat less import is the improvement in dose distributions for target areas (vs photons), which can potentially bring about a better local control. As a result, proton radiotherapy is mainly indicated for paediatric cases, where any development of complications is most likely because of the long lifetimes and the heightened radiosensitivity of healthy tissues. The most recent studies also show that certain subpopulations of patients can benefit from proton beam radiotherapy in cases of widespread cancers such as from the lung or breast. A further advantage is found after conducting a cost-effectiveness analysis whereby proton beam radiotherapy was demonstrated as a cost-effective procedure, with both lowered costs for treating complications and indirect costs. By the term ‘development’ as used herein, it is understood that there is a need to open another proton therapy centre in Poland; this question however being left open in the presented article. Nevertheless, before taking such a high-level decision, the following requires consideration: the working experience garnered by the existing Cyclotron Centre at Bronowice (CCB), outcomes from current prospective clinical trials and, above all, delivering appropriately managed and coordinated oncological care for cancer patients in Poland regarding multi-centre collaboration between specialists.

Craniopharyngiomas are benign intracranial tumors located in the sellar and suprasellar region. Their size and extent of invasion into surrounding structures vary considerably. While the majority of craniopharyngiomas on presentation are between 1–3 cm without hypothalamic invasion, a significant proportion of patients present with ‘giant’ craniopharyngiomas of >4cm in dimension with large cystic extension through the 3rd ventricle. These tumors pose a challenge both for surgical resection as well as for radiation therapy. Proton beam therapy (PBT) has become the preferred standard of care after subtotal resection of pediatric craniopharyngiomas. In the setting of giant craniopharyngioma, the use of proton therapy allows a reduction of dose to surrounding normal brain, but changes in cyst volume can result in either under-coverage of tumor or excess dose to surrounding brain, an effect further magnified by the sharp gradients associated with proton dose distributions. In this case report we describe the proton treatment planning and intra-treatment monitoring of two patients with giant craniopharyngiomas with largest pre-operative of dimension 6cm, and 9cm, respectively, and 6cm and 5.5cm, respectively, pre-radiation. Both patients had drains inserted to Ommaya reservoirs. We performed surveillance imaging during RT utilizing spiral computer tomography (CT) on a weekly basis and reconstructed the treatment dose on the surveillance CTs to ensure target coverage and normal tissue sparing. We compared the dosimetry in these cases for PBT versus intensity-modulated radiation therapy, characterized the cyst evolution during treatment in 3 dimensions, and define an optimized protocol for treatment planning and intra-treatment monitoring.

Purpose: Dual-energy CT (DECT) has been shown to derive stopping power ratio (SPR) map with higher accuracy than conventional single energy CT (SECT) by obtaining the energy dependence of photon interactions. However, DECT is not as widely implemented as SECT in proton radiation therapy simulation. This work presents a learning-based method to synthetize DECT images from SECT for proton radiation therapy. Methods: The proposed method uses a residual attention generative adversarial network. Residual blocks with attention gates were used to force the model focus on the difference between DECT maps and SECT images. To evaluate the accuracy of the method, we retrospectively investigated 20 head-and-neck cancer patients with both DECT and SECT scans available. The high and low energy CT images acquired from DECT acted as learning targets in the training process for SECT datasets and were evaluated against results from the proposed method using a leave-one-out cross-validation strategy. To evaluate our method in the context of a practical application, we generated SPR maps from sDECT using physics-based dual-energy stoichiometric method and compared the maps to those generated from DECT. Results: The synthesized DECT images showed an average mean absolute error around 30 Hounsfield Unit (HU) across the whole-body volume. The corresponding SPR maps generated from synthetic DECT showed an average normalized mean square error of about 1% with reduced noise level and artifacts than those from original DECT. Conclusions: The accuracy of the synthesized DECT image by our machine-learning-based method was evaluated on head and neck patient, and potential feasibility for proton treatment planning and dose calculation was shown by generating SPR map using the synthesized DECT., Comment: arXiv admin note: text overlap with arXiv:2003.09058

Bakgrund: Varje år insjuknar 300 barn i cancer varav cirka 30% av dessa diagnostiseras med hjärntumör. Protonstrålning har sedan 2015 varit ett bra behandlingsalternativ för att minska seneffekterna av strålningen. I dagsläget görs all protonstrålning i Uppsala. Barn med cancer vill vara delaktiga i sin vård och behandling och ålderanpassad information är då viktigt. Syfte: Att beskriva barnsjuksköterskans erfarenhet av att förbereda barn med hjärntumör inför protonstrålning på annan ort. Metod: Sju stycken kvalitativa intervjuer genomfördes med sjuksköterskor. Insamlat material analyserades med kvalitativ innehållsanalys (Elo och Kyngäs 2008). Resultat: Resultatet presenterar tre kategorier: Att nå barnet beskriver vikten av att ha barnet i fokus och anpassa informationen utifrån individen. Att möta utmaningar belyser tidens betydelse för hur förberedelserna blir, att det upplevdes som svårare att förbereda barn när det utförs på annan ort. Att inge trygghet beskriver sjuksköterskans roll att vara en trygg punkt för familjen samt att se till hela familjen. Konklusion: Konklusionen av studien är att barnsjuksköterskorna är medvetna om vikten av att göra barn delaktiga i förberedelser för att främja hälsa samt att tidens påverkan spelar in när sjuksköterskan ska förbereda och nå fram till barnet. Background: Every year, 300 children are diagnosed with cancer, of which about 30% are diagnosed with brain tumor. Proton radiation therapy has been a good treatment alternative since 2015 to reduce the late effects of radiation. At the moment, all proton radiation therapy in Sweden is carried out in Uppsala. Children with cancer want to participate in their care and treatment and age-appropriate information is therefore important. Purpose: To describe the pediatric nurse's experience in preparing children with brain tumors for proton radiation therapy in another location. Method: Seven qualitative interviews were conducted with nurses. Collected material was analyzed with qualitative content analysis (Elo & Kyngäs, 2008). Result: The result presents three categories: Reaching the child describes the importance of having the child in focus and adapting the information based on the individual. Facing challenges highlights the importance of time and how it affects the preparations, it was perceived as more difficult to prepare children getting treatment in another location. Providing security describes the nurse's role to be a safe point for the family and to look after the whole family. Conclusion: The conclusion of the study is that the pediatric nurses are aware of the importance of children’s’ participation in their preparation, to promote health and that time plays an influential role in the preparation and the nurse’s ability to connect with the children.

Background: Child life therapists provide patient education for children undergoing radiation therapy to assist in coping with and understanding their treatment. Objective: This proof-of-concept study aimed to determine the feasibility of incorporating a 360-degree video tour via a virtual reality system for children scheduled to receive radiation therapy. The secondary objective was to qualitatively describe each subject’s virtual reality experience. Methods: Children aged ≥13 years scheduled to receive proton radiation therapy were included in the study. Subjects watched the 360-degree video of the radiation therapy facility in an immersive virtual reality environment with a child life therapist experienced in coaching children receiving radiation therapy and completed a survey after the tour. Results: Eight subjects consented to participate in the study, and six subjects completed the 360-degree video tour and survey. All the enrolled patients completed the tour successfully. Two subjects did not complete the survey. Two subjects requested to pause the tour to ask questions about the facility. Five subjects said the tour was helpful preparation before undergoing proton radiation therapy. Subjects stated that the tour was helpful because “it showed [them] what’s to come” and was helpful to see “what it’s like to lay in the machine.” One subject said, “it made me feel less nervous.” Six subjects stated that they would like to see this type of tour available for other areas of the hospital, such as diagnostic imaging rooms. None of the subjects experienced nausea or vomiting. Conclusions: The 360-degree video tour allowed patients to explore the treatment facility in a comfortable environment. Participants felt that the tour was beneficial and would appreciate seeing other parts of the hospital in this manner.

11550 Background: RPS often have local recurrence (LR) after surgery. Preoperative radiation (RT) to 50.4 Gy can reduce LR risk but is not uniformly effective, especially after (+) margin resections. Therefore, we conducted a multi-institutional, prospective Phase II study to assess efficacy and tolerability of preop IMPT with selective dose escalation to 63 GyRBE to the posterior RPS margin (clinical target volume [CTV] 2) at high risk for (+) margins to further reduce the risk of LR. This dose was tolerable in a prior phase I study (DeLaney T et al, 2017, PMID:28740917). Methods: Primary RPS patients (pts) >18 years received preop IMPT, 50.4 GyRBE in 28 fractions (fx) of 1.8 GyRBE to CTV1 (tumor plus adjacent tissue at risk of subclinical disease) with SIB to CTV2 to 63.0 GyRBE in 28 fx of 2.25 GyRBE. Pts with high-grade tumors could get chemotherapy(CTX) prior to IMPT. To avoid treatment delay, 11 fx of IMRT x-rays could be substituted for IMPT. Pts had restaging and surgery 4-8 weeks after IMPT. Primary study endpoint was local tumor control. Secondary endpoints included clinical and pathologic response, surgical margin status, and disease-free and overall survival. Results: We accrued 60 pts from January 2016 to February 2021. Histology: 35 liposarcoma(LPS) (19 dediff and 16 well diff), 22 leiomyosarcoma(LMS), and 3 undifferentiated pleomorphic sarcoma. IMPT was delivered per protocol in all pts. 51 pts have had surgery, 5 are awaiting surgery, and 4 had no surgery due to metastases(DM) on preop imaging. 22 pts had (+) margins. 2 pts had > 75% necrosis. With 23-month median (range 1-52 months) follow-up after start of RT, there were two LRs. A dediff LPS pt had a well diff LPS LR 26 months postop, resected, and is disease-free. A renal vein/IVC LMS pt treated with CTX and IMPT had LR and DM 4 months postop and died from disease. Surgical Clavien-Dindo morbidity scores: 0(21), 1(9), 2(8), 3a (4), 3b(4), 4a(2), 4(b)1, 5(2); the periop deaths were from sepsis(pneumonia) and duodenal ulcer. The grade 3-4 periop morbidity included abscess(3), treated by catheter(2) or operative(1) drainage, prolonged hospital stays (2 pts with IVC LMS), small bowel obstruction (1), and late sigmoid colon anastomotic failure (1). Readmissions for lymphopenia(1), pneumoperitoneum (1), and volume overload (1). One late neuropathy was seen in a Type II diabetic pt with transient postop weakness after femoral nerve dissection who later had significant lower extremity weakness 3.75 years postop. Study was amended to reduce IMPT dose in diabetic pts. Conclusions: Preoperative IMPT with selective dose escalation to 63 GyRBE to the high risk posterior RPS margin is feasible. Early local control results with this approach appear promising. Some peri-operative morbidity was noted but appears to be in the expected range for RPS resections. Clinical trial information: NCT01659203.

Proton beam therapy (PBT) potentially allows for improved sparing of normal tissues, hopefully leading to decreased late side effects in children. Using a national registry, we sought to perform a patterns-of-care analysis for children receiving PBT for primary malignancies of the central nervous system (CNS).Using the National Cancer Data Base, we identified pediatric patients with primary CNS malignancies that were diagnosed between 2004 and 2012. We used a standard t test for comparison of means and χWe identified 4637 pediatric patients receiving radiation therapy from 2004 to 2012, including a subset of 267 patients treated with PBT. We found that PBT use increased with time from1% in 2004 to 15% in 2012. In multivariate logistical regression, we found the following to be predictors of receipt of PBT: private insurance, the highest income bracket, younger age, living in a metropolitan area, and residing200 miles from a radiation treatment facility (P.05).We noted the proportion of children receiving PBT to be significantly increasing over time from1% to 15% from 2004 to 2012. We also observed important disparities in receipt of PBT based on socioeconomic status. Children from higher-income households and with private insurance were more likely to use this expensive technology. As we continue to demonstrate the potential benefits of PBT in children, efforts are needed to expand the accessibility of PBT for children of all socioeconomic backgrounds and regions of the country.

Purpose Proton radiation therapy (PRT) is a standard treatment of uveal melanoma. PRT patients undergo implantation of ocular tantalum markers (OTMs) for treatment planning. Ultra-high-field MRI is a promising technique for 3D tumor visualization and PRT planning. This work examines MR safety and compatibility of OTMs at 7.0 Tesla. Methods MR safety assessment included deflection angle measurements (DAMs), electromagnetic field (EMF) simulations for specific absorption rate (SAR) estimation, and temperature simulations for examining radiofrequency heating using a bow-tie dipole antenna for transmission. MR compatibility was assessed by susceptibility artifacts in agarose, ex vivo pig eyes, and in an ex vivo tumor eye using gradient echo and fast spin-echo imaging. Results DAM (α

Customized intraoral devices help the radiation oncologist minimize the adverse effects of radiation and maximize the tumor control rate by keeping the anatomic structures in a consistent position during each fraction of radiation treatment. This article illustrates the fabrication of a bolus-type positioning device for a combined intraoral/extraoral defect treated with proton radiation therapy.

The specific aim for the characterization of the lithium formate dosimetry system is to determine response and stability in a proton beam. The long-term goal for this investigation is an audit system for proton therapy like the end-to-end dose determinations performed for radiotherapy with photons. For a 150-MeV proton beam, the dose response was found to be linear in the dose interval 0-8.8 Gy. The accuracy of dose reconstruction was controlled in a blind test, in which the dose of 6.63 Gy was measured in samples irradiated with a real dose of 6.70 Gy. The stability was determined by irradiations of sets of four dosimeters every week during 1 month and analyzed at the same day thereafter. The fitting of the fading curve was done with a second-order polynomial resulting in a 6.6% lower value compared to the reference after 31 d. Funding Agencies|Swedish Cancer foundation [110 322]

Proton radiation therapy has been used clinically since 1952, and major advancements in the last 10 years have helped establish protons as a major clinical modality in the cancer-fighting arsenal. Technologies will always evolve, but enough major breakthroughs have been accomplished over the past 10 years to allow for a major revolution in proton therapy. This paper summarizes the major technology advancements with respect to beam delivery that are now ready for mass implementation in the proton therapy space and encourages vendors to bring these to market to benefit the cancer population worldwide. We state why these technologies are essential and ready for implementation, and we discuss how future systems should be designed to accommodate their required features.

Background The primary treatment for head and neck adenoid cystic carcinoma (ACC) is surgery. Infrequently, however, ACC's propensity for perineural and base of skull invasion can preclude definitive surgical management. We present our experience with proton radiation therapy (RT) and concurrent platinum-based chemotherapy. Methods Nine patients with unresectable node-negative, nonmetastatic head and neck ACC received definitive proton RT and concurrent cisplatin. Outcomes and toxicities were recorded. A systematic review of the literature was performed. Results Median follow-up was 27 months (range, 9.2–48.3 months). Four patients achieved complete response at the primary site, and an additional 4 patients achieved stabilization of local disease. Only 1 patient developed local disease progression. Four patients had 5 acute grade 3 (G3) toxicities, and 1 patient developed a chronic G4 optic nerve disorder. Conclusion Our preliminary results suggest proton RT and concurrent chemotherapy is a definitive treatment option for select patients with head and neck ACC. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

Proton radiation therapy is an effective modality for cancer treatments, but the cost of proton therapy is much higher compared to conventional radiotherapy and this presents a formidable barrier to most clinical practices that wish to offer proton therapy. Little attention in literature has been paid to the costs associated with collimators, range compensators and hypofractionation. The objective of this study was to evaluate the feasibility of cost-saving modifications to the present standard of care for proton treatments for prostate cancer. In particular, we quantified the dosimetric impact of a treatment technique in which custom fabricated collimators were replaced with a multileaf collimator (MLC) and the custom range compensators (RC) were eliminated. The dosimetric impacts of these modifications were assessed for 10 patients with a commercial treatment planning system (TPS) and confirmed with corresponding Monte Carlo simulations. We assessed the impact on lifetime risks of radiogenic second cancers using detailed dose reconstructions and predictive dose-risk models based on epidemiologic data. We also performed illustrative calculations, using an isoeffect model, to examine the potential for hypofractionation. Specifically, we bracketed plausible intervals of proton fraction size and total treatment dose that were equivalent to a conventional photon treatment of 79.2 Gy in 44 fractions. Our results revealed that eliminating the RC and using an MLC had negligible effect on predicted dose distributions and second cancer risks. Even modest hypofractionation strategies can yield substantial cost savings. Together, our results suggest that it is feasible to modify the standard of care to increase treatment efficiency, reduce treatment costs to patients and insurers, while preserving high treatment quality.