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Purpose: In modern conformal radiation therapy of distal esophageal cancer, target coverage can be affected by variations in the diaphragm position. We investigated if daily position verification (PV) extended by a diaphragm position correction would optimize target dose coverage for esophageal cancer treatment.Methods and Materials: For 15 esophageal cancer patients, intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans were computed. Displacements of the target volume were correlated with diaphragm displacements using repeated 4-dimensional computed tomography images to determine the correction needed to account for diaphragm variations. Afterwards, target coverage was evaluated for 3 PV approaches based on: (1) bony anatomy (PV_B), (2) bony anatomy corrected for the diaphragm position (PV_BD) and (3) target volume (PV_T).Results: The cranial-caudal mean target displacement was congruent with almost half of the diaphragm displacement (y = 0.459x), which was used for the diaphragm correction in PV_BD. Target dose coverage using PV_B was adequate for most patients with diaphragm displacements up till 10 mm (>= 94% of the dose in 98% of the volume [D-98%]). For larger displacements, the target coverage was better maintained by PV_T and PV_BD. Overall, PV_BD accounted best for target displacements, especially in combination with tissue density variations (D-98%: IMPT 94% +/- 5%, VMAT 96% +/- 5%). Diaphragm displacements of more than 10 mm were observed in 22% of the cases.Conclusions: PV_B was sufficient to achieve adequate target dose coverage in case of small deviations in diaphragm position. However, large deviations of the diaphragm were best mitigated by PV_BD. To detect the cases where target dose coverage could be compromised due to diaphragm position variations, we recommend monitoring of the diaphragm position before treatment through online imaging. (C) 2021 Elsevier Inc. All rights reserved.

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.

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research. (c) 2021 Elsevier Inc. All rights reserved.

The capabilities of electret ion chambers to measure non-target absorbed dose during radio- therapy treatment was investigated for the first time. During radiotherapy, non-target doses can be classified as one of three approximate dose levels: high doses, intermediate doses and low doses. Low doses (

Purpose For treatment of rectal cancer, pencil beam scanning proton therapy (PBS-PT) may reduce radiation exposure to normal tissues compared with 3-dimensional conformal photon radiation therapy (3DCRT) or volumetric modulated arc photon radiation therapy (VMAT). The purpose of this study was to report the clinical implementation and dosimetric analysis of preoperative short-course PBS-PT for rectal cancer. Methods and Materials Eleven patients with stage IIA-IVB rectal cancer received preoperative short-course (25 Gy in 5 fx) PBS-PT between 2018 and 2019 preceding curative-intent total mesorectal excision. PBS-PT plans were generated using single-field optimization with 2 posterior-oblique fields. Verification computed tomography scans were performed on the first 3 days of treatment. Each patient had a backup 3DCRT and VMAT plan. Results Clinical target volume coverage was similar between PBS-PT, 3DCRT, and VMAT. PBS-PT had statistically significant reductions in dose to the small bowel, large bowel, bladder, and femoral heads across multiple dosimetric parameters. All patients completed PBS-PT as planned without need for replanning. All computed tomography verification scans demonstrated good target coverage with clinical target volume V100 > 95%. Conclusions Preoperative short-course PBS-PT has been successfully implemented and offers a significant reduction of dose to normal tissues. Prospective studies are warranted to evaluate if dosimetric advantages translate into clinical benefit.

A novel wide-field electron arc technique with a scatterer is implemented for widespread Kaposi’s sarcoma (KS) in the distal extremities. Monte Carlo beam modeling for electron arc beams was established to achieve in-vivo measurement data. We enrolled one patient with recurrent KS on the lower extremities who had been treated with photon radiation therapy. The 4- and 6-MeV electron arc plans were created, and then compared to two photon plans: two opposite photon beam and volumetric modulated arc with bolus. Compared to the two photon techniques, the electron arc plans resulted in superior dose saving to normal organs beneath the skin region, although it shows inferior coverage and homogeneity for PTV. The electron arc treatment technique with scatterer was successfully implemented for the treatment of widespread KS in the distal extremities with lower radiation exposure to the normal organs beyond the skin lesions, which could be a treatment option for recurrent skin cancer in the extremities.

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.

Purpose In photon radiation therapy, computed tomography (CT) numbers are converted into values for mass density (MD) or relative electron density to water (RED). CT-MD or CT-RED calibration tables are relevant for human body dose calculation in an inhomogeneous medium. CT-MD or CT-RED calibration tables are influenced by patient imaging (CT scanner manufacturer, scanning parameters, and patient size), the calibration process (tissue-equivalent phantom manufacturer, and selection of tissue-equivalent material), differences between tissue-equivalent materials and standard tissues, and the dose calculation algorithm applied; however, a CT number calibration audit has not been established. The purposes of this study were to develop a postal audit phantom, and to establish a CT number calibration audit process. Methods A conventional stoichiometric calibration conducts a least square fit of the relationships between the MD, material weight, and measured CT number, using two parameters. In this study, a new stoichiometric CT number calibration scheme has been empirically established, using three parameters to harmonize the calculated CT number with the measured CT number for air and lung tissue. In addition, the suitable material set and the minimal number of materials required for stoichiometric CT number calibration were determined. The MDs and elemental weights from the International Commission on Radiological Protection Publication 110 were used as standard tissue data, to generate the CT-MD and CT-RED calibration tables. A small-sized, CT number calibration phantom was developed for a postal audit, and stoichiometric CT number calibration with the phantom was compared to the CT number calibration tables registered in the radiotherapy treatment planning systems (RTPSs) associated with five radiotherapy institutions. Results When a least square fit was performed for the stoichiometric CT number calibration with the three parameters, the calculated CT number showed better agreement with the measured CT number. We established stoichiometric CT number calibration using only two materials because the accuracy of the process was determined not by the number of used materials but by the number of elements contained. The stoichiometric CT number calibration was comparable to the tissue-substitute calibration, with a dose difference less than 1%. An outline of the CT number calibration audit was demonstrated through a multi-institutional study. Conclusions We established a new stoichiometric CT number calibration method for validating the CT number calibration tables registered in RTPSs. We also developed a CT number calibration phantom for a postal audit, which was verified by the performances of multiple CT scanners located at several institutions. The new stoichiometric CT number calibration has the advantages of being performed using only two materials, and decreasing the difference between the calculated and measured CT numbers for air and lung tissue. In the future, a postal CT number calibration audit might be achievable using a smaller phantom.

Radiation induced cavernomas among children with medulloblastoma are common following external beam radiation (XRT) treatment with either photon or proton beams. However, with the increased utilization of proton beam therapy over the last decade we sought to determine if there was any difference in the development or natural history of these cavernous malformations (CM) or CM-like lesions. We performed a retrospective analysis of 79 patients from 2003 to 2019 who had undergone resection of medulloblastoma and subsequent XRT (30 photon or 49 proton beam therapy). The average age of patients at radiation treatment was 8.7 years old. Average follow up for patients who received photon beam therapy was 105 months compared to 56.8 months for proton beam therapy. A total of 68 patients (86.1%) developed post-radiation CMs, including 26 photon and 42 proton patients (86.7% and 85.7% respectively). The time to cavernoma development was significantly different, with a mean of 40.2 months for photon patients and 18.2 months for proton patients (p = 1.98 x 10-4). Three patients, one who received photon and two who received proton beam radiation, required surgical resection of a cavernoma. Although CM or CM-like lesions are detected significantly earlier in patients after receiving proton beam therapy, there appears to be no significant difference between the two radiation therapy modalities in the development of significant CM requiring surgical resection or intervention other than continued follow up and surveillance.

The paper by Raptis et al. concludes that proton therapy has an advantage over photon therapy with respect to the induction of a second cancer. Furthermore, the authors conclude that physiological movements and radiobiological parameters do not affect the general trend of lower risk associated with proton therapy. The work is based on a modeling framework which is different from most previously used models on the same subject. This invited commentary puts the findings of the paper in context with other published modeling studies on second cancer risk after proton and photon radiation therapy for breast cancer.

Computed tomography (CT) data are required to calculate the dose distribution in a patient’s body. Generally, there are two CT number calibration methods for commercial radiotherapy treatment planning system (RTPS), namely CT number‐relative electron density calibration (CT‐RED calibration) and CT number‐mass density calibration (CT‐MD calibration). In a previous study, the tolerance levels of CT‐RED calibration were established for each tissue type. The tolerance levels were established when the relative dose error to local dose reached 2%. However, the tolerance levels of CT‐MD calibration are not established yet. We established the tolerance levels of CT‐MD calibration based on the tolerance levels of CT‐RED calibration. In order to convert mass density (MD) to relative electron density (RED), the conversion factors were determined with adult reference computational phantom data available in the International Commission on Radiological Protection publication 110 (ICRP‐110). In order to validate the practicability of the conversion factor, the relative dose error and the dose linearity were validated with multiple RTPSes and dose calculation algorithms for two groups, namely, CT‐RED calibration and CT‐MD calibration. The tolerance levels of CT‐MD calibration were determined from the tolerance levels of CT‐RED calibration with conversion factors. The converted RED from MD was compared with actual RED calculated from ICRP‐110. The conversion error was within ±0.01 for most standard organs. It was assumed that the conversion error was sufficiently small. The relative dose error difference for two groups was less than 0.3% for each tissue type. Therefore, the tolerance levels for CT‐MD calibration were determined from the tolerance levels of CT‐RED calibration with the conversion factors. The MD tolerance levels for lung, adipose/muscle, and cartilage/spongy‐bone corresponded to ±0.044, ±0.022, and ±0.045 g/cm3, respectively. The tolerance levels were useful in terms of approving the CT‐MD calibration table for clinical use.

Purpose/Objective(s) The degree of lymphopenia has been linked with negative impact on outcomes in patients undergoing radiation therapy (RT) for stage III non-small cell lung cancer (NSCLC). Proton therapy, by virtue of reducing integral dose, can possibly help mitigate risk of lymphopenia as demonstrated in patients with glioblastoma and esophageal cancer. This study sought to analyze the effects of intensity modulated proton therapy (IMPT) in limiting degree of lymphopenia in patients with stage III NSCLC when compared to those treated with photon-based volumetric-modulated arc therapy (VMAT). Materials/Methods Under IRB approval, we retrospectively analyzed 82 stage III NSCLC patients treated definitively with concurrent chemoradiation from January 2014–December 2019 with either IMPT or VMAT. Data on baseline demographics, clinical tumor volume (CTV) values and lymphocyte counts just prior to RT and immediately post-RT were collected. Grade 3 Lymphopenia was defined as ALC Results 36 pts were treated with IMPT and remaining with VMAT (46 patients). Nearly 40% of our stage III NSCLC patient population self-identified as black (N = 31), were predominantly male (N = 45), with an ECOG PS of either 0 or 1 (N = 69; 84%). Patients that underwent IMPT were less likely to be black (78%vs.22%; P = 0.012) and were older (Median age 73 vs 65 years; P = 0.001). There was no difference between mean CTV size of IMPT (419 cc) or VMAT (362 cc) patients (P = 0.36). The incidence of Grade 3 or higher lymphopenia was 39% in VMAT and 36% in IMPT group, though the difference did not reach statistical significance (P = 0.78). Similarly, the mean percent change in ALC from pre-RT to post-RT was lower with IMPT compared to VMAT, though not reaching statistical significance, 61.1% vs 55.6%, respectively (P = 0.22). Conclusion In our analysis of uniformly treated patients with stage III NSCLC, IMPT had no significant impact in reducing the incidence of severe lymphopenia when compared to VMAT. Future analyses should analyze a larger patient population to assess if the marginal protective effect seen has clinical impact on outcomes.

As a radioresistant lesion, chordoma has historically been considered a tumor that is not amenable to radiation therapy. However, beginning in the 1980s, evidence began to develop demonstrating that doses >70Gy could improve local control. Since that time, more advanced technologies have been developed that enable the delivery of therapeutic radiation doses while minimizing toxicities to adjacent tissues, such as the spinal cord and bowel. Evidence from series using these new focused modalities now suggests that radiation therapy in the adjuvant setting may improve local tumor control independent of surgical margin – the classic determinant of local progression-free survival. Evidence is also building that supports the use of focused photon radiation modalities in the neoadjuvant, definitive-intent, and salvage therapy roles. Here we review the new technologies and therapeutic paradigms that have enabled radiotherapy to become a routine part of the therapeutic plan for patients with chordoma of the vertebral column and sacrum.

Purpose: Proton therapy of esophageal cancer is superior to photon radiation therapy in terms of normal tissue sparing. However, respiratory motion and anatomical changes may compromise target dose coverage owing to density changes, geometric misses, and interplay effects. Here we investigate the combined effect on clinical target volume (CTV) coverage and compare proton therapy with intensity modulated radiation therapy (IMRT). Methods and Materials: This study includes 26 patients with esophageal cancer previously treated with IMRT planned on 4-dimensional computed tomography (4D-CT). For each patient, 7 proton pencil beam scanning (PBS) plans were created with different field configurations and optimization strategies. The effect of respiration was investigated by calculating the phase doses, 4D dose, and 4D dynamic dose (including interplay effects). The effect of anatomical changes was investigated by recalculating all plans on all phases of a 4D-CT surveillance scan. Results: The most robust PBS plans were achieved using 2 posterior beams requiring coverage of planning target volume (PTV) and simultaneously using robust optimization (RO) of CTV (2PAPTVRO), resulting in only 1 patient showing V95%CTV RO), 10 patients showed underdosage. For IMRT, 2 patients showed underdosage. Interplay effects reduced V95%CTV significantly when delivering only 1 fraction, but the effects generally averaged out after 10 fractions. The effect of interplay was significantly larger for RO-only plans compared with plans optimized with RO combined with PTV coverage. Combining the effect of anatomical changes and respiration on the 4D-CT surveillance scan resulted in V95%CTV PTVRO, 16 2LPRO, and 8 IMRT patients. Conclusions: PBS using posterior beam angles was more robust to anatomical changes and respiration than IMRT. The effect of respiration was enhanced when anatomical changes were present. Single fraction interplay effects deteriorated the dose distribution but were averaged out after 10 fractions.

Purpose Proton therapy is a limited resource that is not available to all patients who may benefit from it. We investigated combined proton-photon treatments, in which some fractions are delivered with protons and the remaining fractions with photons, as an approach to maximize the benefit of limited proton therapy resources at a population level. Methods and Materials To quantify differences in normal-tissue complication probability (NTCP) between protons and photons, we considered a cohort of 45 patients with head and neck cancer for whom intensity modulated radiation therapy and intensity modulated proton therapy plans were previously created, in combination with NTCP models for xerostomia and dysphagia considered in the Netherlands for proton patient selection. Assuming limited availability of proton slots, we developed methods to optimally assign proton fractions in combined proton-photon treatments to minimize the average NTCP on a population level. The combined treatments were compared with patient selection strategies in which patients are assigned to single-modality proton or photon treatments. Results There is a benefit of combined proton-photon treatments compared with patient selection, owing to the nonlinearity of NTCP functions; that is, the initial proton fractions are the most beneficial, whereas additional proton fractions have a decreasing benefit when a flatter part of the NTCP curve is reached. This effect was small for the patient cohort and NTCP models considered, but it may be larger if dose-response relationships are better known. In addition, when proton slots are limited, patient selection methods face a trade-off between leaving slots unused and blocking slots for future patients who may have a larger benefit. Combined proton-photon treatments with flexible proton slot assignment provide a method to make optimal use of all available resources. Conclusions Combined proton-photon treatments allow for better use of limited proton therapy resources. The benefit over patient selection schemes depends on the NTCP models and the dose differences between protons and photons.

Objective: To evaluate the biological effectiveness of dose associated with interruption time; and propose the dose compensation method based on biological effectiveness when an interruption occurs during photon radiation therapy. Methods: The lineal energy distribution for human salivary gland tumor was calculated by Monte Carlo simulation using a photon beam. The biological dose (Dbio) was estimated using the microdosimetric kinetic model. The dose compensating factor with the physical dose for the difference of the Dbio with and without interruption (Δ) was derived. The interruption time (τ) was varied to 0.1, 0.2, 0.3, 0.4, 0.5, 1, 2, 3, 4, 5, 10, 20, 30, 40, 50, 75, and 120 min. The dose per fraction and dose rate varied from 2 to 8 Gy and 0.1 to 24 Gy/min, respectively. Results: The maximum Δ with 1 Gy/min occurred when the interruption occurred at half the dose. The Δ with 1 Gy/min at half of the dose was over 3% for τ >= 20 min for 2 Gy, τ = 10 min for 5 Gy, and τ = 10 min for 8 Gy. The maximum difference of the Δ due to the dose rate was within 3% for 2 and 5 Gy, and achieving values of 4.0% for 8 Gy. The dose compensating factor was larger with a high dose per fraction and high-dose rate beams. Conclusion: A loss of biological effectiveness occurs due to interruption. Our proposal method could correct for the unexpected decrease of the biological effectiveness caused by interruption time. Advances in knowledge: For photon radiotherapy, the interruption causes the sublethal damage repair. The current study proposed the dose compensation method for the decrease of the biological effect by the interruption.

Purpose Biological treatment plan evaluation does not currently consider second cancer induction from peripheral doses associated to photon radiotherapy. The aim is to propose a methodology to characterize the therapeutic window by means of an integral radiobiological approach, which considers not only Tumour Control Probability ( TCP ) and Normal Tissue Complication Probability ( NTCP ) but also Secondary Cancer Probability ( SCP ). Methods Uncomplicated and Cancer-Free Control Probability ( UCFCP ) function has been proposed assuming a statistically uncorrelated response for tumour and normal tissues. The Poisson’s and Lyman’s models were chosen for TCP and NTCP calculations, respectively. SCP was modelled as the summation of risks associated to photon and neutron irradiation of radiosensitive organs. For the medium (>4 Gy) and low dose regions, mechanistic and linear secondary cancer risks models were used, respectively. Two conformal and intensity-modulated prostate plans at 15 MV (same prescription dose) were selected to illustrate the UCFCP features. Results UCFCP exhibits a bell-shaped behaviour with its maximum inside the therapeutic window. SCP values were not different for the plans analysed (∼2.4%) and agreed with published epidemiological results. Therefore, main differences in UCFCP came from differences in rectal NTCP (18% vs 9% for 3D-CRT and IMRT, respectively). According to UCFCP values, the evaluated IMRT plan ranked first. Conclusions The level of SCP was found to be similar to that of NTCP complications which reinforces the importance of considering second cancer risks as part of the possible late sequelae due to treatment. Previous concerns about the effect of peripheral radiation, especially neutrons, in the induction of secondary cancers can be evaluated by quantifying the UCFCP .

Pancreatic tumors show large interfractional position variation. In addition, changes in gastrointestinal gas volumes and body contour take place over the course of radiation therapy. We aimed to quantify the effect of these anatomical changes on target dose coverage, for the clinically used fiducial marker‐based patient position verification and, for comparison, also for simulated bony anatomy‐based position verification. Nine consecutive patients were included in this retrospective study. To enable fraction dose calculations on cone‐beam CT (CBCT), the planning CT was deformably registered to each CBCT (13–15 per patient); gas volumes visible on CBCT were copied to the deformed CT. Fraction doses were calculated for the clinically used 10 MV VMAT treatment plan (with for the planning target volume (PTV): D98% = 95%), according to fiducial marker‐based and bony anatomy‐based image registrations. Dose distributions were rigidly summed to yield the accumulated dose. To evaluate target dose coverage, we defined an iCTV +5 mm volume, i.e., the internal clinical target volume (iCTV) expanded with a 5 mm margin to account for remaining uncertainties including delineation uncertainties. We analyzed D98%, Dmean, and D2% for iCTV +5 mm and PTV (i.e., iCTV plus 10 mm margin). We found that for fiducial marker‐based registration, differences between fraction doses and planned dose were minimal. For bony anatomy‐based registration, fraction doses differed considerably, resulting in large differences between planned and accumulated dose for some patients, up to a decrease in D98% of the iCTV +5 mm from 95.9% to 85.8%. Our study shows that fractionated photon irradiation of pancreatic tumors is robust against variations in body contour and gastrointestinal gas, with dose coverage only mildly affected. However, as a result of interfractional tumor position variations, target dose coverage can severely decline when using bony anatomy for patient position verification. Therefore, the use of intratumoral fiducial marker‐based daily position verification is essential in pancreatic cancer patients.

At our institution, a multifaceted approach is used to reduce general anesthetic (GA) use for children receiving photon radiation therapy (RT) as standard-of-care treatment. The purpose of this study was to evaluate the effectiveness of our methods.Patients treated as part of the pediatric radiation therapy program from 2010 to 2018 were retrospectively reviewed. GA use was defined as need for intravenous propofol or inhaled gaseous anesthetic for at least 1 simulation or RT session. Methods to reduce GA use included presence of a dedicated pediatric nurse for procedural preparation, audiovisual distraction (television during RT), and 2-way audio communication with caregivers.There were 779 unique patients who received RT over 14 163 fractions of radiation. GA utilization was 90% in those under age 3, 28% in those age 3 to 6, 1% in those age 7 to 11, and1% in those ≥12 years of age. Four years of age is a cutoff age at which the majority of patients switch from needing GA (56.6% for those aged 3) to not needing GA (29.8% for those aged 4). Younger age, use of total body irradiation, and craniospinal irradiation were independently associated with requiring GA.Using methods designed to reduce GA use, most children aged 4 years or older were able receive RT awake. Our GA rates compare favorably to other literature reports; thus, pediatric RT centers should consider adopting specific interventions to reduce GA use.

Radiation therapy (RT) exerts multiple effects on the immune system; in particular RT can serve as an in situ vaccine to either prime new anti-tumor T cell responses, or to induce new responses. We and many others showed that these propitious effects appear to counter-balanced to some degree by immunosuppressive effects, including the expansion of regulatory T cells (Treg), recruitment of myeloid derived suppressive cells (MDSC), and induction of Trex which mitigates the pro-inflammatory effects of STING pathway activation. Carbon-ion radiation therapy (CiRT) is an emerging therapeutic modality based on data showing that heavy ions may improve dosimetry and decrease toxicity to normal tissues. Currently, CiRT is performed at a limited number of centers, thus its immunological effects remain relatively understudied. To address this knowledge gap, we used an orthotopic, syngenic murine model to compare the relative immunological effects of CiRT to conventional photon radiation therapy (PhRT). At short follow-up times post RT, PhRT decreased the prevalence of T cells in the TME at all doses examined, whilst CiRT appeared to be relatively lymphocyte sparing. Higher doses of CiRT increased the secretion of multiple pro-inflammatory cytokines to a greater degree than did PhRT. Consistent with our prior results, both modalities increased Treg infiltration; although this was less apparent with CiRT. Although these are early studies with several caveats, the results support the hypothesis that CiRT may have differential immunological effects than those mediated by PhRT. Citation Format: Charles G. Drake. Differential immunological effects of carbon-ion versus photon radiation therapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-012.

Arc-therapy is a dose delivery technique regularly applied in photon radiation therapy, and is currently subject of great interest for proton therapy as well. In this technique, proton beams are aimed at a tumor from different continuous ranges of incident directions (so called ‘arcs’). This technique can potentially yield a better dose conformity around the tumor and a very low dose in the surrounding healthy tissue. Currently, proton-arc therapy is performed by rotating a proton gantry around the patient, adapting the normally used dose-delivery method to the arc-specific motion of the gantry. Here we present first results from a feasibility study of the conceptual design of a new static fast beam delivery device/system for proton-arc therapy, which could be used instead of a gantry. In this novel concept, the incident angle of proton beams can be set rapidly by only changing field strengths of small magnets. This device eliminates the motion of the heavy gantry and related hardware. Therefore, a reduction of the total treatment time is expected. In the feasibility study presented here, we concentrate on the concept of the beam transport. Based on several simple, but realistic assumptions and approximations, proton tracking calculations were performed in a 3D magnetic field map, to calculate the beam transport in this device and to investigate and address several beam-optics challenges. We propose and simulate corresponding solutions and discuss their outcomes. To enable the implementation of some usually applied techniques in proton therapy, such as pencil beam scanning, energy modulation and beam shaping, we present and discuss our proposals. Here we present the concept of a new idea to perform fast proton arc-scanning and we report on first results of a feasibility study. Based on these results, we propose several options and next steps in the design.

Purpose The aim of this study was to review institutional outcomes for advanced thyroid cancers treated with fast neutron radiation therapy (FNRT) and photon radiation therapy (RT). Methods and materials In all, 62 consecutive patients were analyzed. Fifty-nine had stage IV disease. Twenty-three were treated with FNRT and 39 with photon RT. Median follow-up was 14 months. The primary endpoint was overall survival (OS). Results There was no significant difference in median OS between FNRT and photon RT (26 vs 16 months; P = .49). Patients with well-differentiated histologies had superior median OS with photon RT (17 vs 69 months; P = .04). There was a nonsignificant trend toward improved OS with FNRT for medullary and anaplastic histologies. Conclusions Outcomes in this study are in line with historical results. There is an apparent detriment in OS with FNRT for well-differentiated histologies and a trend toward improved OS with medullary and anaplastic histologies that warrants further investigation.

Purpose Mixed beam electron-photon radiation therapy (MBRT) is an emerging technique that has the potential to reduce dose to normal tissue while improving target coverage for cancer sites with superficial tumors. Advances in optimization algorithms and robotic linear accelerators have made the creation and delivery of complex MBRT plans realistic without the need for special additional collimators, devices, or resetup of the patient. However, no study has been performed on the robustness of MBRT dose distributions to patient setup errors. Intensity-modulated delivery of other charged particles such as protons have been shown to require robust planning techniques to maintain adequate target coverage under positioning errors. We therefore assess the sensitivity of MBRT treatment plans to positioning uncertainties when created under the traditional planning target volume (PTV)-based planning paradigm and present a novel optimization model for the creation of robust MBRT plans. Methods The column generation method was applied to robust MBRT treatment planning by deriving the pricing problem for stochastic and "worst case" minimax optimization models, two common formulations of robustness. Robust treatment plans were created for two patient cases representative of the cancer sites which stand to benefit from MBRT: soft tissue sarcoma (STS) irradiation and chest wall irradiation with deep-seated internal mammary, axillary, and supraclavicular nodes (CW-N). For both patient cases, beamlet dose distributions for electrons and photons were generated for positioning shifts in six directions, ± 5 mm ( x ^ , y ^ , z ^ ) in addition to a nominal unshifted scenario, for a total of seven sets of beamlets. Robust plans were created by specifying dose coverage constraints to the clinical target volume (CTV), as opposed to the PTV. Comparisons were performed against traditional PTV-based plans created with a single set of unshifted beamlets. Results The dose distributions of traditional PTV-based MBRT plans showed significant degradation in target coverage homogeneity when patient positioning errors were considered. For both cancer sites, cold spots below 95% and hot spots above 108% of the prescription dose appeared within the CTV when shifting the patient by 5 mm, corresponding to the margin added to the CTV to form the PTV. In contrast, CTV-based robust plans created with the new optimization model maintained target coverage within the 95%-108% limits, for all positioning errors. Conclusion The quality of MBRT treatment plans created using a traditional PTV-based optimization model was highly sensitive to patient positioning errors. For both patient cases, positioning errors resulted in perturbations to the nominal dose distributions which would have rendered PTV-based plans clinically unacceptable. In contrast, CTV-based robust plans were able to maintain adequate target coverage under all positioning error scenarios considered. We therefore conclude that to ensure the fidelity of the dose distribution delivered to the patient, robust optimization is critical when creating MBRT plans.

INTRODUCTION: Proton beam radiotherapy (PBRT) reduces exposure of healthy tissue to radiation, which may minimize late effects in pediatric brain tumor patients. This study compared social, cognitive, and academic outcomes in children treated with PBRT versus photon radiotherapy (XRT). METHODS: Survivors who were >1 year post-radiation (M=6.5, SD=3.27 years) completed cognitive (processing speed, working memory, language, attention, executive function, memory) and academic (reading, writing, math fluency) testing. Parents completed questionnaires assessing survivors’ social functioning. RESULTS: XRT (n=29) and PBRT (n=54) groups did not differ on demographic/clinical variables (68.7% male, M age-at-treatment=7.8 years, 51.8% infratentorial tumor, 55.0% craniospinal RT, median RT dose to tumor=54.0 Gy), except for age-at-evaluation (PBRT M=13.23 years, XRT M=16.39 years; p=0.01) and follow-up interval (PBRT M=5.05 years, XRT M=8.59 years; p0.05). The PBRT group was also rated as having better social functioning (p

Background The purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were treated with PBT in our institution. In addition, we evaluated the correlation between toxicities and dosimetric parameters, especially the doses to normal lung or heart tissue, to clarify the clinical advantage of PBT over photon radiation therapy. Methods A total of 37 consecutive patients with Stage III thoracic ESCC who had received PBT with or without concurrent chemotherapy between October 2012 and December 2015 were evaluated in this study. The dose distributions of PBT were compared with those of dummy 3-dimensional conformal radiation therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT), focusing especially on the doses to organs at risk, such as normal lung and heart tissue. Results Of the 37 patients, the data from 27 patients were analyzed. Among these 27 patients, four patients (15%) developed grade 2 pericardial effusion as a late toxicity. None of the patients developed grade 3 or worse acute or late pulmonary and cardiac toxicities. When the dosimetric parameters between PBT and planned 3DCRT were compared, all the PBT domestic variables for the lung dose except for lung V10 GyE and V15 GyE were significantly lower than those for the dummy 3DCRT plans, and the PBT domestic variables for the heart dose were also significantly lower than those for the dummy 3DCRT plans. When the PBT and IMRT plans were compared, all the PBT domestic variables for the doses to the lung and heart were significantly lower than those for the dummy IMRT plans. Regarding the correlation between the grades of toxicities and the dosimetric parameters, no significant correlation was seen between the occurrence of grade 2 pericardial effusion and the dose to the heart. Conclusions When the dosimetric parameters of the dose distributions for the treatment of patients with locally advanced stage III ESCC were compared between PBT and 3DCRT or IMRT, PBT enabled a significant reduction in the dose to the lung and heart, compared with 3DCRT or IMRT.

Chordomas and chondrosarcomas of the base of the skull are difficult to manage because of their location and proximity to critical structures. Since recurrence after surgery alone is common, planning of multimodal therapy, including postoperative radiation, is often essential. Although postoperative radiation improves local control of tumor after surgery, its efficacy may be limited by proximity of critical structures such as the brainstem and optic pathways. Significant improvement in photon irradiation techniques, such as intensity-modulated radiation therapy, three-dimensional conformal radiation therapy, and tomotherapy, are permitting delivery of higher dose to tumor while sparing critical normal structures from radiation exposure above tolerable levels.

BACKGROUND Proton therapy in pediatrics may improve the risk/benefit profile of radiotherapy at a greater upfront financial cost, but it may prove to be cost effective if chronic medical complications can be avoided. Tools to assist with decision making are needed to aid in selecting pediatric patients for protons, and cost-effectiveness models can provide an objective method for this. METHODS A Markov cohort-simulation model was developed to assess the expected costs and effectiveness for specific radiation doses to the hypothalamus with protons versus photons in pediatric patients. Costing data included cost of investment and the diagnosis and management of growth hormone deficiency. Longitudinal outcomes data were used to inform risk parameters for the model. With costs in 2012 US dollars and effectiveness measured in quality-adjusted life years, incremental cost-effectiveness ratios were used to measure outcomes. RESULTS Proton therapy was cost effective for some scenarios based on the difference in hypothalamic sparing. Although some scenarios were not cost effective, others were not only cost effective for proton therapy but also demonstrated that protons were cost saving compared with photons. CONCLUSIONS The current results provide the first evidence-based guide for identifying children with brain tumors who may benefit the most from proton therapy with respect to endocrine dysfunction. Proton therapy may be more cost effective for scenarios in which radiation dose to the hypothalamus can be spared, but protons may not be cost effective when tumors are involving or directly adjacent to the hypothalamus if there is a high dose to this structure. Cancer 2015;121:1694–1702. © 2015 American Cancer Society.

Background: Osteosarcoma is the most frequent primary malignant bone tumour, and its incidence is higher in children and adolescents, for whom it represents more than 10% of solid cancers. Despite the introduction of adjuvant and neo-adjuvant chemotherapy that markedly increased the success rate in the treatment, aggressive surgery is still needed and a considerable percentage of patients do not survive due to recurrences or early metastases. Boron Neutron Capture Therapy (BNCT), an experimental radiotherapy, was investigated as a treatment that could allow a less aggressive surgery by killing infiltrated tumour cells in the surrounding healthy tissues. BNCT requires an intense neutron beam to ensure irradiation times of the order of 1h. In Italy, a Radio Frequency Quadrupole (RFQ) proton accelerator has been designed and constructed for BNCT, and a suitable neutron spectrum was tailored by means of Monte Carlo calculations. This paper explores the feasibility of BNCT to treat osteosarcoma using this neutron source based on accelerator. Methods: The therapeutic efficacy of BNCT was analysed evaluating the dose distribution obtained in a clinical case of femur osteosarcoma. Mixed field dosimetry was assessed with two different formalisms whose parameters were specifically derived from radiobiological experiments involving in vitro UMR-106 osteosarcoma cell survival assays and boron concentration assessments in an animal model of osteosarcoma. A clinical case of skull osteosarcoma treated with BNCT in Japan was re-evaluated from the point of view of dose calculation and used as a reference for comparison. Results: The results in the case of femur osteosarcoma show that the RFQ beam would ensure a suitable tumour dose painting in a total irradiation time of less than an hour. Comparing the dosimetry between the analysed case and the treated patient in Japan it turns out that doses obtained in the femur tumour are at least as good as the ones delivered in the skull osteosarcoma. The same is concluded when the comparison is carried out taking into account osteosarcoma irradiations with photon radiation therapy. Conclusions: The possibility to apply BNCT to osteosarcoma would allow a multimodal treatment consisting in neo-adjuvant chemotherapy, high-LET selective radiation treatment and a more conservative surgery. Fil: Bortolussi, Silva. University of Pavia; Italia Fil: Postuma, Ian. University of Pavia; Italia Fil: Protti, Nicoletta. University of Pavia; Italia Fil: Provenzano, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina Fil: Ferrari, Cinzia. University of Pavia; Italia Fil: Cansolino, Laura. University of Pavia; Italia Fil: Dionigi, Paolo. University of Pavia; Italia Fil: Galasso, Olimpio. University of Catanzaro; Italia Fil: Gasparini, Giorgio. University of Catanzaro; Italia Fil: Altieri, Saverio. University of Pavia; Italia Fil: Miyatake, Shin Ichi. Osaka Medical College; Japón Fil: González, Sara Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina

While often managed with surgery alone, patients with thymic malignancies with high-risk features may benefit from adjuvant radiation therapy but are at risk for late toxicities. Previously, the risk of major cardiac events (MCEs) was reported to increase by 7% per one Gray (Gy) to the heart. In this study, we compare dose to organs at risk (OARs) with intensity-modulated (IMRT) versus proton beam therapy (PBT). We hypothesize a decrease risk of predicted MCEs with PBT.Patients requiring adjuvant therapy for thymic malignancies were treated with double scattered proton beam therapy (DS-PBT). Clinical backup IMRT plans were generated. Predicted MCEs were calculated based on median dose to the heart. A Wilcoxon rank sum test was used for statistical comparisons.Twenty-two consecutive patients were evaluated. DS-PBT resulted in statistically significant decreases in dose to the heart, lungs, left ventricle, esophagus, and spinal cord (all p ≤ .01). The increase in risk of MCEs from 0 to ≥20 years was lower with PBT (74% versus 135%, p = .04).DS-PBT results in decreased dose to OARs and may reduce the risk of MCEs compared with IMRT. Long-term follow-up is required to assess for clinical benefit from DS-PBT.

AimThe aim of this work was to map the characteristics of (n,γ) and (γ,n) reactions in a high energy photon radiation therapy.BackgroundPhotoneutrons produced in the high energy X-Ray radiation therapy may damage patients and staff. It is due to high RBE of the produced neutrons according to their energy and isotropic emission. Characterization of the photoneutrons can help us in appropriate shielding.Materials and methodsThis study focused on the photoneutron and capture gamma ray phenomena. Characteristics such as dose value, fluence and spectra of both the neutrons and the by produced prompt gamma ray were described.Results and discussionNeutron and prompt gamma spectra in different points showed the neutrons to be thermalized when increasing the distance from the linac. Energy of the neutrons changed from about 0.6MeV at the isocentre to around 10−08MeV at the outer door position. Although the neutrons were found as fast neutrons, their spectra showed they were thermal neutrons at the outer door position. Additionally, it was seen that the energy of the gamma rays is higher than the scattered X-ray energy. The energy of gamma rays was seen to be up to 10MeV while the linac photons had energy lower than 1MeV. Neutron source strength obtained in this work was in good agreement with the published data, which may be a confirmation of our simulation accuracy.ConclusionThe study showed that the Monte Carlo simulation can be applied in the radiotherapy and industrial radiation works as a useful and precise estimator. We also concluded that the dose from the prompt gamma ray at the outer door location is higher than the scattered radiation from the linac and should be considered in the shielding.

The goal of radiation therapy is to deliver tumoricidal dose to clinical target volume (CTV) while sparing organs-at-risk (OAR). We hypothesize that the joint use of proton and photon radiation therapy via appropriate hybrid proton-photon inverse planning method will be more favorable than proton or photon therapy alone, in terms of optimized combination of CTV coverage and OAR sparing. This work develops hybrid proton-photon inverse optimization method that simultaneously optimizes proton and photon variables. To account for delivery uncertainty, proton dose is targeted at CTV using robust optimization, and photon dose is targeted at either CTV using robust optimization or planning target volume (PTV) using the same setup shifts. The optimization objectives enforce OAR sparing and uniform CTV coverage for the total dose, while imposing uniform-dose regularization at targets for both the proton and photon component in order for both components to be individually deliverable. The hybrid problem with dose-volume-histogram (DVH) constraints is nonconvex and solved by iterative convex relaxations of DVH constraints and alternating direction method of multipliers (ADMM). Preliminary results suggest the hybrid proton-photon planning potentially improves proton or photon planning in terms of optimized combination of CTV coverage and OAR sparing.

Radiation therapy (RT) that involves the cardiac silhouette is associated with a 9-fold increase in incident heart failure (HF) among women with breast cancer (BC). Pathologically, RT-induced cardiotoxicity leads to myocardial fibrosis, atrophy and a reduction in cardiomyocyte mass; cardiac magnetic

Volumetric modulated arc therapy (VMAT) is a relatively new treatment modality for dynamic photon radiation therapy. Pre-treatment quality assurance (QA) is necessary and many efforts have been made to apply electronic portal imaging device (EPID)-based IMRT QA methods to VMAT. It is important to verify the gantry rotation speed during delivery as this is a new variable that is also modulated in VMAT. In this paper, we present a new technique to perform VMAT QA using an EPID. The method utilizes EPID cine mode and was tested on Varian TrueBeam in research mode. The cine images were acquired during delivery and converted to dose matrices after profile correction and dose calibration. A sub-arc corresponding to each cine image was extracted from the original plan and its portal image prediction was calculated. Several analyses were performed including 3D γ analysis (2D images + gantry angle axis), 2D γ analysis, and other statistical analyses. The method was applied to 21 VMAT photon plans of 3 photon energies. The accuracy of the cine image information was investigated. Furthermore, this method’s sensitivity to machine delivery errors was studied. The pass rate (92.8 ± 1.4%) for 3D γ analysis was comparable to those from Delta 4 system (99.9 ± 0.1%) under similar criteria (3%, 3 mm, 5% threshold and 2 ◦ angle to agreement) at 6 MV. The recorded gantry angle and start/stop MUs were found to have sufficient accuracy for clinical QA. Machine delivery errors can be detected through combined analyses of 3D γ , gantry angle, and percentage dose difference. In summary, we have developed and validated a QA technique that can simultaneously verify the gantry angle and delivered MLC fluence for VMAT treatment.This technique is efficient and its accuracy is comparable to other QA methods. (Some figures may appear in colour only in the online journal)

Objective Skull base chordomas (SBC) are characterized by persistent progression. Conventional radiation following resection increases 5- and 10-year local control (LC) to 36 and 23 %, respectively. Patients treated with protons result in 10-year LC of 50 %. Brainstem dose constraints have inhibited higher prescription doses with photons. We reviewed our experience using high-dose fractionated stereotactic photon radiation therapy (HD-FSRT) to 81 Gy for SBC.

BACKGROUND Proton therapy for treatment for high-risk neuroblastoma may offer sparing of organs at risk (OAR) when compared to intensity-modulated X-ray therapy (IMXT). PROCEDURE Double-scattered proton plans and IMXT plans delivering 2,160 cGy to the primary tumor site and other residual disease were developed for 13 consecutive HR-NBL patients. Radiation doses to target volumes and OAR were calculated to determine the optimal modality for each. RESULTS All patients received radiation (5/13 ≥ 2 sites). No patient has experienced local recurrence or clinical organ toxicity. Coverage was excellent using both protons and IMXT: median % dose delivered to 95% clinical target volume was 99% and 100%, respectively. For nine patients with lateralized disease, proton therapy offered sparing of the contralateral kidney both with regard to median dose and dose to 20% (median

This review considers the management of motion in photon radiation therapy. An overview is given of magnitudes and variability of motion of various structures and organs, and how the motion affects images by producing artifacts and blurring. Imaging of motion is described, including 4DCT and 4DPET. Techniques for monitoring motion in real time by use of surrogates are reviewed. Treatment planning for various motion-management treatment delivery strategies is discussed, including choice of planning image, treatment field margins and dose calculation. Imaging techniques displaying motion in the treatment room for pre-treatment as well as real-time imaging for localization and verification are covered, and their use for various motion-management treatment delivery techniques is discussed. Use of motion management for different treatment sites—breast, lung and other sites—is elaborated, and gating, breath-hold and beam tracking strategies are described. Suggestions are given for breast and lung for practicable protocols for routine clinical use of motion management, including decision strategies. Finally, a perspective of the future of motion management in photon radiation therapy is given.