Photon Beam Radiotherapy Research Articles

Tumor Regression with 5-Aminolevulinic Acid (5-ALA)-Mediated Radiodynamic Therapy (RDT) Using Different Megavoltage Energies

5-aminolevulinic acid (5-ALA) accumulates in target tumor cells, where it is metabolized to a photosensitizer - protoporphyrin IX (PpIX). Cherenkov light induced by high-energy photon beams effectively activates the PpIX due to the Soret band. The activated photosensitizers lead to cellular toxicities to kill malignant tumor cells by converting surrounding tissue oxygens into singlet oxygens. Radiodynamic therapy (RDT) utilizes cellular damage caused by both radiation dose and activated photosensitizer. The emission of Cherenkov light was observed higher with higher energy irradiation in phantom and ex-vivo tissues. Therefore, using an in-vivo mouse model, this study aimed to investigate the efficacy and energy dependency of RDT combined with 5-ALA and different ranges of megavoltage photon irradiation. In order to investigate individual and synergistic effects of 5-ALA administration and radiation treatment, the tumors (n = 344) were randomized into eight groups: control (untreated), 5-ALA only, 6-, 15-, and 45-MV conventional radiation treatment (RT) only, 6-, 15-, and 45-MV RDT. 4 Gy in a single fraction was delivered to the tumors using three different energy photons for RT only and RDT groups. 5-ALA was systemically injected into 5-ALA only and RDT groups at 100 mg/kg by tail-vein 4 hours before irradiation for endogenous PpIX accumulation in the tumor. Tumor growth was measured using a 1.5 T MR scanner on the day of treatment (prior to the treatment), 3, 7, and 14 days post-treatment. Two-way repeated ANOVA with Bonferroni correction was used to compare each treatment group to determine the statistically significant difference in tumor growth. A total of 45 MV RDT resulted in the most significant decrease in tumor growth by 58.8 ± 3.4 %, 58.0 ± 3.0 %, and 55.0 ± 3.0 % compared to 5-ALA, 45 MV RT, and control group on 7 days post-treatment (P<0.001), respectively. Moreover, a synergistic effect of 45 MV RDT causes a 47.1-54.1 % additional decrease in tumor growth toward the effective treatment outcome. Compared to the different energies, 45 MV RDT resulted in a 52.2 ± 3.1 % and 19.7 ± 7.2 % decrease in tumor growth compared to 6 MV RDT and 15 MV RDT on 7 days post-treatment, respectively (P<0.001), whereas the conventional RT was not. Radiodynamic therapy using 5-ALA administration and 45MV photon beam irradiation resulted in the most significant tumor growth control. A photon energy dependency was observed in radiodynamic therapy. 45MV photon beams showed greater in activating PpIX, improving the synergistic effects of radiation dose and activated photosensitizer than the other energies. The preliminary results provide a foundation for new innovative treatment strategies that have the potential to improve cancer treatment.

Feasibility study of a scintillation sheet-based detector for fluence monitoring during external photon beam radiotherapy

PurposeThis study evaluated the properties of a scintillation sheet-based dosimetry system for beam monitoring with high spatial resolution, including the effects of this system on the treatment beam. The dosimetric characteristics and feasibility of this system for clinical use were also evaluated. MethodsThe effects of the dosimetry system on the beam were evaluated by measuring the percentage depth doses, dose profiles, and transmission factors. Fifteen treatment plans were created, and the influence of the dosimetry system on these clinical treatment plans was evaluated. The performance of the system was assessed by determining signal linearity, dose rate dependence, and reproducibility. The feasibility of the system for clinical use was evaluated by comparing intensity distributions with reference intensity distributions verified by quality assurance. ResultsThe spatial resolution of the dosimetry system was found to be 0.43 mm/pixel when projected to the isocenter plane. The dosimetry system attenuated the intensity of 6 MV beams by about 1.1%, without affecting the percentage depth doses and dose profiles. The response of the dosimetry system was linear, independent of the dose rate used in the clinic, and reproducible. Comparison of intensity distributions of evaluation treatment fields with reference intensity distributions showed that the 1%/1 mm average gamma passing rate was 99.6%. ConclusionsThe dosimetry system did not significantly alter the beam characteristics, indicating that the system could be implemented by using only a transmission factor. The dosimetry system is clinically suitable for monitoring treatment beam delivery with higher spatial resolution than other transmission detectors.

The effect of eight weeks of moderate-intensity endurance training on serum levels of troponin I and B-type natriuretic peptide in radiotherapy rats

Background and aims: One of the most important potential problems of radiotherapy is the heart problem caused by this treatment. Therefore, this research aimed to investigate the effect of 8 weeks of moderate-intensity endurance training on the serum levels of troponin I (TNI) and brain (B-type) natriuretic peptide (BNP) in rats undergoing radiation therapy. ] Methods: In this experimental study, 32 male rats (4-6 months) were randomly divided into four groups of eight, including healthy control (C), aerobic training (AT), radiotherapy (RT), and AT+RT groups. First, rats were anesthetized with ketamine-xylazine solution (K: 60-90 kg/mg, Z: 6-10 kg/mg) and then located on a Plexiglas plate with a thickness of 1 cm. Photon beam RT was performed using X-rays with a dose of 11 Gy from an Elekta compact linear accelerator (Elekta Compact 6-MV China). AT program was performed for eight weeks, five days a week, and one session a day for 60 minutes (70-75% of maximal oxygen consumption). Finally, one-way ANOVA was run to examine the research variables. Results: The results showed that there was no significant difference between the groups in terms of the TNI level (P=0.23). However, a significant difference was found in the amount of BNP between the RT and C groups (P=0.009). In addition, no significant difference was reported in terms of BNP between AT+RT with AT (P=0.99), RT (P=0.32), and C (P=0.69) groups, as well as between AT with RT (P=0.1) and C (P=0.99) groups. Conclusion: Overall, radiation therapy caused a significant increase in BNP, but it had no significant effect on TNI. Aerobic training did not significantly affect TNI and BNP in healthy rats and those undergoing radiation therapy.

Does radiotherapy effect the voltage output of cardiac implantable electronic devices (CIEDs)?

Abstract Funding Acknowledgements Type of funding sources: None. Purpose Current guidelines for the management of patients undergoing radiotherapy with cardiac implantable electronic devices (CIEDs) were published in 1994. They recommend that the total dose received by the device should be estimated before treatment, devices should not be placed in the direct radiation beam and the cumulative dose should not exceed 2Gy to any part of a pacemaker (0.5Gy for ICDs). This is because radiotherapy can cause malfunctions in cardiac implantable devices. At doses higher than this, relocation of the device is recommended. Device malfunctions are suggested to correlate with a beam energy of ≥10MV. One malfunction that poses a high risk to patients is a change in voltage output amplitude. This study assessed if low-energy flattening filter and high energy flattening filter-free photon beam radiation caused a change in the voltage output amplitude of cardiac implantable devices. Method 40 cardiac implantable devices were divided into two treatment groups and irradiated in vitro with a cumulative 48Gy dose of 6MV radiation at 600MU/min in 8 fractions or a 48Gy dose of 10MV radiation at 2400MU/min. The voltage output amplitude of all devices was collected using an oscilloscope and an amplitude change of ≥25% was classed as a clinically significant malfunction. Results In the 6X treatment group, 0/19 devices showed a clinically significant change. No statistical significant difference was found between the median peak voltage output amplitude before fraction 1 and after fraction 8 (U = 149.5, p = 0.3733, n =19). In the 10MV treatment group, 2/21 devices showed a clinically significant change. These devices showed a voltage output amplitude increase of 28.07% and 36.97%. However, no statistical significant difference was found between the median peak voltage output amplitude before and after radiation (U = 149.5, P = 0.0746, n = 21). Although insignificant, there was clearly a larger change across all devices in the 10FFF group compared to the 6X group. Results were not statistically significant between manufacturers but defibrillators were statistically significantly more likely to malfunction than pacemakers. Conclusion The recommended dose of radiotherapy for patients with a CIED should be carefully considered on an individual basis. Due to neutron production and its effect on rapid access memory (RAM) and complementary metal oxide semiconductor (CMOS) circuitry, high-energy ≥10MV radiation can affect the voltage output amplitude, despite its statistical insignificance. Based on this limited report it is unlikely that the voltage output amplitude of CIEDs will be affected by clinically relevant doses of radiotherapy, but it may have long term implications on battery life. These results could eliminate the risk of increased infection due to relocation of devices, provide patients with optimised treatment and enable a more effective service for improved patient management.

Evaluating the linearity response for a PVA/MWCNT-OH nanocomposite dosimeter in photon beam of linear accelerator

A nanocomposite dosimeter based on Polyvinyl Alcohol/Multi-Walled Carbon Nanotube Hydroxyl (PVA/MWCNT-OH) was fabricated and the performance characteristics were measured in this work. A digital insulator tester was used to determine the electrical percolation threshold for nanocomposite material. The parallel plate pure polyvinyl alcohol and 0.02 wt% PVA/MWCNT-OH nanocomposite dosimeter with 0.40 cm3 sensitive volume were fabricated using the solution method. The Transmission Electron Microscopy (TEM) analysis was studied and confirmed the appropriate dispersion state of the inclusions. Siemens Oncor a linear medical accelerator was used to exposure. The variation in the collected electric charge during the irradiation was considered and recorded via the electrometer as the dosimeter response of the nanocomposite at the energies of 6 and 18 MV. The characteristics of the dosimeter under the reference photon beam field size including leakage current of dosimeter, bias polarity, linearity of response, energy dependency on dosimeter response were investigated. Results showed that the dosimeter response and sensitivity were linear at various monitor units (MUs) ranging from 50 to 500 MUs photon beam radiation dose.

Analytical models for external photon beam radiotherapy out-of-field dose calculation: a scoping review.

A growing body of scientific evidence indicates that exposure to low dose ionizing radiation (< 2 Gy) is associated with a higher risk of developing radio-induced cancer. Additionally, it has been shown to have significant impacts on both innate and adaptive immune responses. As a result, the evaluation of the low doses inevitably delivered outside the treatment fields (out-of-field dose) in photon radiotherapy is a topic that is regaining interest at a pivotal moment in radiotherapy. In this work, we proposed a scoping review in order to identify evidence of strengths and limitations of available analytical models for out-of-field dose calculation in external photon beam radiotherapy for the purpose of implementation in clinical routine. Papers published between 1988 and 2022 proposing a novel analytical model that estimated at least one component of the out-of-field dose for photon external radiotherapy were included. Models focusing on electrons, protons and Monte-Carlo methods were excluded. The methodological quality and potential limitations of each model were analyzed to assess their generalizability. Twenty-one published papers were selected for analysis, of which 14 proposed multi-compartment models, demonstrating that research efforts are directed towards an increasingly detailed description of the underlying physical phenomena. Our synthesis revealed great inhomogeneities in practices, in particular in the acquisition of experimental data and the standardization of measurements, in the choice of metrics used for the evaluation of model performance and even in the definition of regions considered out-of-the-field, which makes quantitative comparisons impossible. We therefore propose to clarify some key concepts. The analytical methods do not seem to be easily suitable for massive use in clinical routine, due to the inevitable cumbersome nature of their implementation. Currently, there is no consensus on a mathematical formalism that comprehensively describes the out-of-field dose in external photon radiotherapy, partly due to the complex interactions between a large number of influencing factors. Out-of-field dose calculation models based on neural networks could be promising tools to overcome these limitations and thus favor a transfer to the clinic, but the lack of sufficiently large and heterogeneous data sets is the main obstacle.

Development and characterization of a versatile mini-beam collimator for pre-clinical photon beam irradiation.

Interest in spatial fractionation radiotherapy has exponentially increased over the last decade as a significant reduction of healthy tissue toxicity was observed by mini-beam irradiation. Published studies, however, mostly use rigid mini-beam collimators dedicated to their exact experimental arrangement such that changing the setup or testing new mini-beam collimator configurations becomes challenging andexpensive. In this work, a versatile, low-cost mini-beam collimator was designed and manufactured for pre-clinical applications with X-ray beams. The mini-beam collimator enables variability of the full width at half maximum (FWHM), the center-to-center distance (ctc), the peak-to-valley dose ratio (PVDR), and the source-to-collimator distance (SCD). The mini-beam collimator is an in-house development, which was constructed of 10× 40mm2 tungsten or brass plates. These metal plates were combined with 3D-printed plastic plates that can be stacked together in the desired order. A standard X-ray source was used for the dosimetric characterization of four different configurations of the collimator, including a combination of plastic plates of 0.5, 1, or 2mm width, assembled with 1 or 2mm thick metal plates. Irradiations were done at three different SCDs for characterizing the performance of the collimator. For the SCDs closer to the radiation source, the plastic plates were 3D-printed with a dedicated angle to compensate for the X-ray beam divergence, making it possible to study ultra-high dose rates of around 40Gy/s. All dosimetric quantifications were performed using EBT-XD films. Additionally, in vitro studies with H460 cells were carriedout. Characteristic mini-beam dose distributions were obtained with the developed collimator using a conventional X-ray source. With the exchangeable 3D-printed plates, FWHM and ctc from 0.52 to 2.11mm, and from 1.77 to 4.61mm were achieved, with uncertainties ranging from 0.01% to 8.98%, respectively. The FWHM and ctc obtained with the EBT-XD films are in agreement with the design of each mini-beam collimator configuration. For dose rates in the order of several Gy/min, the highest PVDR of 10.09 ± 1.08 was achieved with a collimator configuration of 0.5mm thick plastic plates and 2mm thick metal plates. Exchanging the tungsten plates with the lower-density metal brass reduced the PVDR by approximately 50%. Also, increasing the dose rate to ultra-high dose rates was feasible with the mini-beam collimator, where a PVDR of 24.26 ± 2.10 was achieved. Finally, it was possible to deliver and quantify mini-beam dose distribution patterns in vitro. With the developed collimator, we achieved various mini-beam dose distributions that can be adjusted according to the needs of the user in regards to FWHM, ctc, PVDR and SCD, while accounting for beam divergence. Therefore, the designed mini-beam collimator may enable low-cost and versatile pre-clinical research on mini-beamirradiation.

Trimodality Treatment of Superior Sulcus Non-Small Cell Lung Cancer: An Institutional Series of 47 Consecutive Patients

Treatment of superior sulcus tumors (SST) using concurrent chemoradiation followed by surgery is a current standard. However, due to the rarity of this entity, clinical experience in its treatment remains scarce. Here, we present the results of a large consecutive series of patients treated with concurrent chemoradiation followed by surgery at a single academic institution. The study group included 48 patients with pathologically confirmed SST. The treatment schedule consisted of preoperative 6-MV photon-beam radiotherapy (45-66 Gy delivered in 25-33 fractions over 5-6.5 weeks) and concurrent two cycles of platinum-based chemotherapy. Five weeks after completion of chemoradiation, pulmonary and chest wall resection was performed. From 2006 to 2018, 47 of 48 consecutive patients meeting protocol criteria underwent two cycles of cisplatin-based chemotherapy and concurrent radiotherapy (45-66 Gy) followed by pulmonary resection. One patient did not undergo surgery due to brain metastases that occurred during induction therapy. The median follow-up was 64.7 months. Chemoradiation was well tolerated, with no toxicity-related deaths. Twenty-one patients (44%) developed grade 3-4 side effects, of which the most common was neutropenia (17 patients; 35.4%). Seventeen patients (36.2%) had postoperative complications, and 90-day mortality was 2.1%. Three- and five-year overall survival (OS) were 43.6% and 33.5%, respectively, and three- and five-year recurrence-free survival were 42.1% and 32.4%, respectively. Thirteen (27.7%) and 22 (46.8%) patients had a complete and major pathological response, respectively. Five-year OS in patients with complete tumor regression was 52.7% (95% CI 29.4-94.5). Predictive factors of long-term survival included age below 70 years, complete resection, pathological stage, and response to induction treatment. Chemoradiation followed by surgery is a relatively safe method with satisfactory outcomes.

In Vitro Effects of Photon Beam and Carbon Ion Radiotherapy on the Perineural Invasion of Two Cell Lines of Neurotropic Tumours.

Primary mucosal melanoma (PMM) and pancreatic ductal adenocarcinoma (PDAC) are two aggressive malignancies, characterized by intrinsic radio-chemoresistance and neurotropism, a histological feature resulting in frequent perineural invasion (PNI), supported by neurotrophic factors secreted in the tumour microenvironment (TME), such as neurotrophin-3 (NT-3). Carbon-ion radiotherapy (CIRT) could represent an effective option in unresectable PMM and PDAC. Only a few data about the effects of CIRT on PNI in relation to NT-3 are available in the literature, despite the numerous pieces of evidence revealing the peculiar effects of this type of radiation on tumour cell migration. This in vitro study investigated for the first time the response of PMM and PDAC cells to NT-3 and evaluated the effects of conventional photon beam radiotherapy (XRT) and CIRT on cell viability, proliferation, and migration. Our results demonstrated the greater capacity of C-ions to generally decrease cell viability, proliferation, and migration, while the addition of NT-3 after both types of irradiation determined an increase in these features, maintaining a dose-dependent trend and acting more effectively as a chemoattractant than inductor in the case of migration.

End-to-End QA with Polymer Gel Dosimeter for Photon Beam Radiation Therapy.

With the complexity and high demands on quality assurance (QA) of photon beam radiation therapy, end-to-end (E2E) QA is necessary to validate the entire treatment workflow from pre-treatment imaging to beam delivery. A polymer gel dosimeter is a promising tool for three-dimensional (3D) dose distribution measurement. The purpose of this study is to design a fast "one delivery" polymethyl methacrylate (PMMA) phantom with a polymer gel dosimeter for the E2E QA test of the photon beam. The one delivery phantom is composed of ten calibration cuvettes for the calibration curve measurement, two 10 cm gel dosimeter inserts for the dose distribution measurement, and three 5.5 cm gel dosimeters for the square field measurement. The one delivery phantom holder is comparable in size and shape to that of a human thorax and abdomen. In addition, an anthropomorphic head phantom was employed to measure the patient-specific dose distribution of a VMAT plan. The E2E dosimetry was verified by undertaking the whole RT procedure (immobilization, CT simulation, treatment planning, phantom set-up, imaged-guided registration, and beam delivery). The calibration curve, field size, and patient-specific dose were measured with a polymer gel dosimeter. The positioning error can be mitigated with the one-delivery PMMA phantom holder. The delivered dose measured with a polymer gel dosimeter was compared with the planned dose. The gamma passing rate is 86.64% with the MAGAT-f gel dosimeter. The results ascertain the feasibility of the one delivery phantom with a polymer gel dosimeter for a photon beam in E2E QA. The QA time can be reduced with the designed one delivery phantom.

Paraffin gauze bolus as tissue compensator in photon irradiation for mycosis fungoides – regarding a case study

Abstract Introduction: Total skin electron beam therapy is a treatment option in patients with mycosis fungoides (MF) affecting a significant amount of the body surface. For patients with involvement of soles and interdigital folds, however, this approach is ineffective, requiring alternatives such as localised radiotherapy (RT). Although electron beams are well suited for superficial lesions, on irregular surfaces it provides inadequate tumour coverage and excess dose variance, requiring photon irradiation with tissue compensation. Methods: We present the case of a patient with extensive cutaneous MF with skin lesions spread over both lower limbs and treated on these affected areas with photon beam RT. Long sheets of paraffin gauze dressings were used to create a 0·5-cm-thick bolus. The patient received a single fraction of 8 Gy. In vivo dosimetry using Gafchromic films was performed. Results: After 3 months, a complete response was achieved. In this case, paraffin gauze bolus proved to be an inexpensive, convenient, effective and flexible method for irregular superficial cancer irradiations. Conclusion: Paraffin gauze bolus is a suitable option for irregular contours.

Performance characteristics of a parallel plate dosimeter based on PVA/MWCNT-OH nanocomposite for photon beam radiation

A new homemade Polyvinyl Alcohol/Multi-Walled Carbon Nanotube Hydroxyl (PVA/MWCNT-OH) nanocomposite dosimeter was developed for photon beam radiation in this research. A parallel plate dosimeter with 0.40 cm3 sensitive volume was fabricated with PVA/MWCNT-OH nanocomposite which equipped with necessary connector so that its response against irradiation can be recorded by a standard electrometer. The dosimetric characteristics of the Homemade Nano-Composite (HNC) dosimeter were studied in Secondary Standard Dosimetery Laboratory (SSDL) with Picker V9 Co-60 irradiator. The sensitivity of the HNC dosimeter was about three times higher than reference standard dosimeters (0.35 cm3 Ross parallel plate ion chamber). Other performance tests such as leakage current, linearity response based on radiation dose, saturation response, polarity effect, directional dependence, field size and energy dependence were performed. All results obtained were in good agreement with IEC 60,731 standard. Therefore, the HNC dosimeter is suitable for routine dosimetric procedures in photon beam radiation.

On the sensitivity of PROMs during breast radiotherapy

PurposeTo investigate the sensitivity of patient-reported outcome measures (PROMs) to detect treatment-related side effects in patients with breast cancer undergoing external beam photon radiotherapy. MethodsAs part of daily clinical care, an in-house developed PROM tool was used to assess side effects in patients during a) whole-breast irradiation (WBI) to 40 Gy, b) WBI with a sequential boost of 10 Gy, and c) partial-breast irradiation (PBI) to 40 Gy. Results414 patients participated in this prospective study between October 2020 and January 2022, with 128 patients (31 %) receiving WBI, 241 (58 %) receiving WBI followed by a sequential boost, and 50 patients (12 %) receiving PBI. Significant differences in the reported toxicities (itching, radiation skin reaction, skin darkening, and tenderness and swelling) were reported between the WBI cohorts with and without boost (p < 0.001, p < 0.001, p < 0.001, and p = 0.002, respectively). The comparison of PBI with WBI (no-boost) yielded significant differences for radiation skin reaction (p < 0.001). ConclusionThe results highlight the high sensitivity of PROMs to detect treatment-related side effects in patients with breast cancer. Thus, PROMs may be a valuable tool for quality control and may support evidence-based learning from real-world data originating from daily routine care.

Radioprotective effect of mistletoe extract on intestinal toxicity: in vivo study using adult zebrafish

Purpose The intestine is a dose-limiting organ in the treatment of intra-abdominal cancer. We previously reported that the extract of mistletoe parasites on Quercus had a more potent radioprotective effect than amifostine in reducing the developmental toxicities of zebrafish embryos. In this study, radioprotection against intestinal toxicity was investigated in adult zebrafish. Methods Wild-type adult AB zebrafish were exposed to 45–50 Gy of photon beam irradiation and/or treated with mistletoe extract orally 1 h before. The main endpoints of the study were survival and degree of deformation of the intestinal villi. Results The median follow-up period was 10 d post-irradiation (range: 7–11 d). A total of 105 zebrafish were used, including 42 in the radiation alone, 42 in the radiation and mistletoe arms, and 21 control subjects (mistletoe alone, mock-irradiated arm). The rate of both significant deformity and death was 53% in the radiation-alone arm, whereas the corresponding rate was 30% in the radiation and mistletoe arms. Significant deformity-free survival rates at 10 d post-irradiation in the radiation alone, and radiation and mistletoe arms were 44.7% (95% confidence interval [CI]:20–54.3) and 68.4% (95% CI:53.8–86.8), respectively (p=.046). The radiation and mistletoe arms showed decreased expression of two of three inflammatory genes (IL-1β and IL-6) compared to the radiation alone group (p<.05). Conclusion The radioprotective effect against intestinal toxicity was successfully shown in an adult zebrafish model. This result suggests the possibility of clinical use of mistletoe extract for the treatment of abdominal cancers.

Clinical Outcomes of Medulloblastoma Patients Treated with Proton Radiotherapy: A Systematic Review

<h3>Purpose/Objective(s)</h3> The aim of this study was to comprehensively review all studies examining clinical outcomes of proton therapy for craniospinal irradiation of medulloblastoma, to determine whether theoretical dosimetric advantages of proton therapy have translated into superior clinical outcomes, including survival and toxicities. <h3>Materials/Methods</h3> We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the PubMed (Medline), EMBASE, and Cochrane Library databases (inception to December 2021). The study was registered with PROSPERO, CRD42022302455. Articles in the English language reporting on clinical outcomes of pediatric and/or adult medulloblastoma patients treated with proton therapy were included. Two independent authors screened all titles/abstracts, reviewed full texts and extracted relevant data, with discrepancies resolved by consensus. Individual study quality was scored using Newcastle Ottawa Scale and overall evidence base by GRADE scale. <h3>Results</h3> Thirty-five studies were included, representing 629 unique patients. Publication dates ranged from 2011 to 2021, with the majority (n=32) from the United States. None of the studies were randomized, 12 were comparative, 9 were prospective, 3 mixed and 22 retrospective. Average mean/median follow up was 5.0 years (range = 4 weeks to 12.6 years). The majority of studies (n=19) reported on treatment with passive scatter proton beams exclusively. Average study quality score was 6.08 out of 9 (SD 0.688, median 5). Seven studies scored ≥8/9 on the Newcastle Ottawa Scale; an overall "moderate" GRADE score was assigned. Well-designed comparative cohort studies with adequate follow-up demonstrate superior neurocognitive outcomes, lower incidence of hypothyroidism (23% vs 69%) and reduced acute toxicities (including myelosuppression, esophagitis, diarrhea, weight loss and nausea/vomiting) in patients treated with protons compared to photons. The 10-year cumulative incidence of secondary malignancy is also lower for proton cohorts (2.1-4.9% vs 8%), but did not reach statistical significance in any individual study. Overall survival (10-yr) (85.3-86.9% for standard-risk disease), progression-free survival (10-yr), patterns of failure, and other endocrine outcomes such as incidence of GH deficiency, adrenal insufficiency and precocious puberty were similar to those reported for photon therapy. Quality of life, ototoxicity and incidence of CNS injury were also found to be comparable between proton and photon cohorts, albeit with lower quality of evidence. Overall, quality of evidence was most robust in the domains of intellectual outcomes, endocrinopathies and acute toxicity. <h3>Conclusion</h3> Moderate grade evidence supports proton beam therapy as a preferred treatment for craniospinal irradiation of medulloblastoma based on equivalent disease outcomes and comparable-to-improved toxicity versus photon beam radiotherapy.

Dosimetric Impact on the Flattening Filter and Addition of Gold Nanoparticles in Radiotherapy: A Monte Carlo Study on Depth Dose Using the 6 and 10 MV FFF Photon Beams.

Purpose: This phantom study investigated through Monte Carlo simulation how the dose enhancement varied with depth, when gold nanoparticles (NPs) were added using the flattening filter-free (FFF) photon beams in gold NP-enhanced radiotherapy. Method: A phantom with materials varying from pure water to a mixture of water and gold NPs at different concentrations (3–40 mg/mL) were irradiated by the 6 and 10 MV flattening filter (FF) and FFF photon beams. Monte Carlo simulations were carried out to determine the depth doses along the central beam axis of the phantom up to a depth of 40 cm. The dose enhancement ratio (DER) and FFF enhancement ratio (FFFER) were calculated based on the Monte Carlo results. Results: The DER values were found decreased with an increase of depth and increase of NP concentration in the phantom. For the maximum NP concentration of 40 mg/mL, the DER values decreased 6.9, 12, 4.6 and 7.2% at a phantom depth from 2 to 40 cm, using the 6 MV FF, 6 MV FFF, 10 MV FF and 10 MV FFF photon beams, respectively. The maximum DER values for the 6 MV beams were 1.08 (FF) and 1.14 (FFF), while those for the 10 MV beams were 1.04 (FF) and 1.07 (FFF). When the FF was removed from the linear accelerator head, the FFFER showed a more significant increase of dose enhancement for the 6 MV beams (1.057) than the 10 MV (1.031). Conclusion: From the DER and FFFER values based on the Monte Carlo results, it is concluded that the dose enhancement with depth was dependent on the NP and beam variables, namely, NP concentration, presence of FF in the beam and beam energy. Dose enhancement was more significant when using the lower photon beam energy (i.e., 6 MV), FFF photon beam and higher NP concentration in the study.

Radiation therapy for primary orbital and ocular adnexal lymphoma

ObjectiveTo report the efficacy and toxicity of External beam Radiotherapy (EBRT) as a sole treatment for MALT and Follicular Primary Orbital and Ocular adnexal Lymphoma (POOAL) MethodsRetrospective review of all POOAL patients treated with EBRT utilizing megavoltage photon or electron beam radiotherapy between 2003 and 2015. Patient demographics, tumour extent and pathology, radiotherapy techniques, and treatment outcomes were reviewed. The actuarial rates of tumour control and radiation toxicities were calculated using Kaplan-Meier estimates. ResultsThis study included 167 tumours, of which MALT lymphoma involved 149 (89 %). The conjunctiva and orbit were equally involved as the predominant site (48 %). Megavoltage photon radiotherapy was used in 60 % of predominantly orbital lymphoma and Electron beam with lens shielding in 77 % of the conjunctival lymphoma. The majority (95 %) were treated with a total dose of 25 Gy in 10 fractions. Local control rate was 98 % (CI: 93–100 %) at 5 years. The long-term RT toxicities included dry eye in 27 eyes (16 %) and cataract in 22 (13 %). None of the patients developed significant structural or functional radiation toxicity. ConclusionExternal Beam Radiotherapy, with lens shielding whenever indicated, at a dose of 20–30 Gy delivered over 10–20 fractions is an efficacious and safe primary treatment option for POOAL lymphoma, with excellent local control and low incidence of late manageable ocular toxicities.

Change in surface characteristics and permeability of human enamel after subjecting to radiation therapy.

Radiation-related caries is a complex destructive lesion leading to uncompromising damage of enamel and dentin in patients suffering from head and neck cancer managed with radiotherapy. The purpose of this study was to evaluate the changes in the permeability of enamel and to assess the morphological and chemical changes of teeth surface subjected to 6 MV photon beam irradiation. For this in vitro study, coronal portion of 20 premolars were sectioned mesiodistally into halves and then grouped into two. Samples in group 1 (control) were not subjected to cycles of irradiation and those in group 2 (experimental) were subjected to a cumulative uniform radiation dose of 70 Gray fractioned in 35 fractions with 6 MV photons. The silver nitrate penetration method was used to assess the change in permeability of enamel. The variations in surface topography and mineral content were assessed using scanning electron microscopy with energy dispersive X-ray analysis. Dye penetration scores of surface texture changes were compared between the two groups utilizing the Chi-square test. The change in the elemental levels between enamel surfaces of the two groups was compared using an independent t-test. The application of 6 MV photon radiation did not change enamel permeability and surface topography. However, a noteworthy reduction in the carbon content (P = 0.002) was observed in teeth subjected to irradiation. Though radiation exposure did not alter the enamel permeability and surface topography, it had caused significant chemical compositional changes. Carbon content was significantly reduced in irradiated enamel samples.

P03.05.A Radiation-induced leukoencephalopathy (RIL) in glioma: unique injury dynamics following proton vs photon beam radiotherapy

Abstract Background White matter injury after brain-directed radiotherapy (RT), aka radiation-induced leukoencephalopathy (RIL), is common in brain tumor patients. Differentiation from progressive disease can be challenging. Dosimetric advantages of protons (PRT) over photons (XRT) minimize radiation to healthy brain tissue, potentially limiting radiotoxic sequelae including RIL. We characterized RIL during periods of progression-free survival (PFS) in glioma patients irradiated with either PRT or XRT, hypothesizing that PRT would result in reduced RIL outside of the target field. Material and Methods 34 patients (19 male; mean age = 40.10y) with grade 2/3 gliomas and a history of partial cranial RT were stratified by RT modality [XRT (n=17) vs PRT (n=17)] and matched on 11 criteria [age, sex, tumor type/location/laterality, mutational status (IDH; 1p19q deletion), concurrent/adjuvant chemotherapy, radiation dose/fractions] for retrospective analysis. RIL development was characterized longitudinally for up to 3 years post-RT via analysis of serial MRI T2/FLAIR sequences. A novel RIL scoring system with embedded Fazekas scale was designed to quantify injury severity at both global (whole brain) and hemispheric levels. Results Matched groups did not differ significantly on any demographic or clinical characteristics. Median PFS post-RT was 4.7 (XRT) and 5.1 (PRT) years. The novel RIL scoring system was reliable (intraclass correlation coefficient &amp;gt;0.9). There was a significant increase in global RIL in both XRT [F(3, 57)=8.63, p&amp;lt; .001] and PRT [F(3, 61)=4.69, p&amp;lt; .005] groups over time, relative to baseline (1-month post-RT). A majority [62% (XRT) and 72% (PRT)] developed moderate or severe RIL within 3 years, with the ipsilesional hemisphere more severely affected. Analysis of RIL injury dynamics (i.e., average % change between 1 and 3 years post-RT) at hemispheric level identified radiation modality-specific differences: XRT resulted in greater contralesional hemispheric injury than PRT [F(1, 31)=4.32, p&amp;lt;.05]. This effect was not observed in ipsilesional hemispheres. Conclusion RIL is common in glioma patients and quantifiable by characteristic imaging features, including early onset post-RT, greater ipsilesional injury burden, and progression over time. RIL injury dynamics appear to be radiation modality-specific, whereby XRT causes greater delayed injury in the remote, contralesional hemisphere. These findings may reflect dosimetric differences between protons and photons. The impact of such sequelae on cognitive function is subject of current investigation.

Cellular analysis on the radiation induced bystander effects due to bismuth oxide nanoparticles with 6 MV photon beam radiotherapy

BackgroundThe therapeutic strategies in killing the cancerous tissue while keeping the normal healthy tissue uninterrupted can be further improved by introducing nanoparticles as radiosensitizer in radiotherapy. Nevertheless, healthy cells might still be affected by radiation-induced bystander effect (RIBE) response due the presence of nanoparticles. Thus, the potential negative effects in non-irradiated adjacent cells must be investigated. AimThe current study aims to explore the cellular effects of bismuth oxide nanoparticles (Bi2O3 NPs) on human breast cancer (MCF-7) and human foetal osteoblast (hFOB 1.19) cells due to the RIBE after irradiation with 6 MV clinical photon beam. Materials and methodsThe irradiated-cell conditioned medium (ICCM) treated with and without Bi2O3 NPs from the irradiated cells were collected and then transferred into the non-targeted cells. The ability of the bystander cells to proliferate and their ROS generation were analyzed. DNA status of the cells and the possibility of apoptosis were evaluated using FTIR spectroscopy and MUSE Cell Analyzer, respectively. ResultsThe current study revealed that MCF-7 and hFOB 1.19 bystander cells may continue to proliferate and survive following short and long-term incubation with ICCM treatment with Bi2O3 NPs. The survival rate of the treated bystander cells increased approximately 3%–8% compared to the untreated group. Although the bystander cells exhibited an increase in ROS and apoptosis, the addition of Bi2O3 NPs had no significant detrimental influence on the cells. Variation in the DNA vibrational amplitude detected by FTIR in bystander cells was less than 5% compared to the control group. ConclusionThis study discovered that the application of Bi2O3 NPs as a radiosensitizer did not give a negative impact on the bystander cells. This outcome may give an advantage to the application of Bi2O3 NPs as radiosensitizer in radiotherapy to enhance cancer cells death without introducing further detrimental effects to the non-targeted cells.