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Purpose Intensity-modulated radiotherapy (IMRT) for cervical cancer yields favorable results in terms of oncological outcomes, acute toxicity, and late toxicity. Limited data are available on clinical results with volumetric modulated arc therapy (VMAT). This study’s purpose is to compare outcome and toxicity with VMAT to conventional 3D conformal radiotherapy (3DCRT), giving special consideration to the influence of patient- and treatment-related parameters on side effects. Materials and methods Patients with cervical cancer stage I–IVA underwent radiotherapy alone or chemoradiotherapy using 3DCRT (n = 75) or VMAT (n = 30). Survival endpoints were overall survival, progression-free survival, and locoregional control. The National Cancer Institute Common Terminology Criteria for Adverse Events and the Late Effects of Normal Tissues criteria were used for toxicity assessment. Toxicity and patient- and treatment-related parameters were included in a multivariable model. Results There were no differences in survival rates between treatment groups. VMAT significantly reduced late small bowel toxicity (OR = 0.10, p = 0.03). Additionally, VMAT was associated with an increased risk of acute urinary toxicity (OR = 2.94, p = 0.01). A low body mass index (BMI; OR = 2.46, p = 0.03) and overall acute toxicity ≥grade 2 (OR = 4.17, p Conclusion We demonstrated significant reduction of late small bowel toxicity with VMAT treatment, an improvement in long-term morbidity is conceivable. VMAT-treated patients experienced acute urinary toxicity more frequently. Further analysis of patient- and treatment-related parameters indicates that the close monitoring of patients with low BMI and of patients who experienced relevant acute toxicity during follow-up care could improve late toxicity profiles.

PURPOSE: To develop and implement an efficient and accurate commissioning procedure for small field static beam animal irradiation studies on an MV research linear accelerator (Linatron-M9) using radiochromic gel dosimetry. MATERIALS: The research linear accelerator (Linatron-M9) is a 9 MV linac with a static fixed collimator opening of 5.08 cm diameter. Lead collimators were manually placed to create smaller fields of 2x2 cm(2), 1x1 cm(2) and 0.5x0.5 cm(2). Relative dosimetry measurements were performed, including profiles, percent depth dose (PDD) curves, beam divergence, and relative output factors using various dosimetry tools, including a small volume ionization chamber (A14), GAFCHROMIC™ EBT3 film, and Clearview gel dosimeters. The gel dosimeter was used to provide a 3D volumetric reference of the irradiated fields. The Linatron profiles and relative output factors were extracted at a reference depth of 2 cm with the output factor measured relative to the 2x2 cm(2) reference field. Absolute dosimetry was performed using A-14 ionization chamber measurements, which were verified using a national standards laboratory remote dosimetry service. RESULTS: Absolute dosimetry measurements were confirmed within 1.4% (k = 2, 95% confidence = 5%). The relative output factor of the small fields measured with films and gels agreed with a maximum relative percent error difference between the two methods of 1.1 % for the 1x1 cm(2) field and 4.3 % for the 0.5x0.5 cm(2) field. These relative errors were primarily due to the variability in the collimator positioning. The measured beam profiles demonstrated excellent agreement for beam size (measured as FWHM), within approximately 0.8 mm (or less). Film measurements were more accurate in the penumbra region due to the film’s finer resolution compared with the gel dosimeter. Following the van Dyk criteria, the PDD values of the film and gel measurements agree within 11% in the buildup region starting from 0.5 cm depth and within 2.6 % beyond maximum dose and into the fall-off region for depths up to 5 cm. The 2D beam profile isodose lines agree within 0.5 mm in all regions for the 0.5x0.5 cm(2) and the 1x1 cm(2) fields and within 1 mm for the larger field of 2x2 cm(2). The 2D PDD curves agree within approximately 2% of the maximum in the typical therapy region (1–4 cm) for the 1x1 cm(2) and 2x2 cm(2) and within 5% for the 0.5x0.5 cm(2) field. CONCLUSION: This work provides a commissioning process to measure the beam characteristics of a fixed beam MV accelerator with detailed dosimetric evaluation for its implementation in megavoltage small animal irradiation studies. Radiochromic gel dosimeters are efficient small field relative dosimetry tools providing 3D dose measurements allowing for full representation of dose, dosimeter misalignment corrections and high reproducibility with low inter-dosimeter variability. Overall, radiochromic gels are valuable for fast, full relative dosimetry commissioning in comparison to films for application in high energy small-field animal irradiation studies.

Purpose Treating deep‐seated bulky tumors with traditional single‐field Cerrobend GRID‐blocks has many limitations such as suboptimal target coverage and excessive skin toxicity. Heavy traditional GRID‐blocks are a concern for patient safety at various gantry‐angles and dosimetric detail is not always available without a GRID template in user’s treatment planning system. Herein, we propose a simple, yet clinically useful multileaf collimator (MLC)‐based three‐dimensional (3D)‐crossfire technique to provide sufficient target coverage, reduce skin dose, and potentially escalate tumor dose to deep‐seated bulky tumors. Materials/methods Thirteen patients (multiple sites) who underwent conventional single‐field cerrobend GRID‐block therapy (maximum, 15 Gy in 1 fraction) were re‐planned using an MLC‐based 3D‐crossfire method. Gross tumor volume (GTV) was used to generate a lattice pattern of 10 mm diameter and 20 mm center‐to‐center mimicking conventional GRID‐block using an in‐house MATLAB program. For the same prescription, MLC‐based 3D‐crossfire grid plans were generated using 6‐gantry positions (clockwise) at 60° spacing (210°, 270°, 330°, 30°, 90°, 150°, therefore, each gantry angle associated with a complement angle at 180° apart) with differentially‐weighted 6 or 18 MV beams in Eclipse. For each gantry, standard Millenium120 (Varian) 5 mm MLC leaves were fit to the grid‐pattern with 90° collimator rotation, so that the tunneling dose distribution was achieved. Acuros‐based dose was calculated for heterogeneity corrections. Dosimetric parameters evaluated include: mean GTV dose, GTV dose heterogeneities (peak‐to‐valley dose ratio, PVDR), skin dose and dose to other adjacent critical structures. Additionally, planning time and delivery efficiency was recorded. With 3D‐MLC, dose escalation up to 23 Gy was simulated for all patient's plans. Results All 3D‐MLC crossfire GRID plans exhibited excellent target coverage with mean GTV dose of 13.4 ± 0.5 Gy (range: 12.43–14.24 Gy) and mean PVDR of 2.0 ± 0.3 (range: 1.7–2.4). Maximal and dose to 5 cc of skin were 9.7 ± 2.7 Gy (range: 5.4–14.0 Gy) and 6.3 ± 1.8 Gy (range: 4.1–11.1 Gy), on average respectively. Three‐dimensional‐MLC treatment planning time was about an hour or less. Compared to traditional GRID‐block, average beam on time was 20% less, while providing similar overall treatment time. With 3D‐MLC plans, tumor dose can be escalated up to 23 Gy while respecting skin dose tolerances. Conclusion The simple MLC‐based 3D‐crossfire GRID‐therapy technique resulted in enhanced target coverage for de‐bulking deep‐seated bulky tumors, reduced skin toxicity and spare adjacent critical structures. This simple MLC‐based approach can be easily adopted by any radiotherapy center. It provides detailed dosimetry and a safe and effective treatment by eliminating the heavy physical GRID‐block and could potentially provide same day treatment. Prospective clinical trial with higher tumor‐dose to bulky deep‐seated tumors is anticipated.

BACKGROUND Multimodality treatment for head and neck cancer leads to substantial functional and esthetic impairment mainly manifested as radiation-induced skin fibrosis (RIF) in combination with volumetric defects and reduction in neck mobility. This study assessed the impact of lipotransfer as part of secondary surgical procedure(s) in patients treated for head and neck malignancies. METHODS Retrospective analysis was performed between 2005 and 2016. All patients with a history of head and neck malignancy, multimodal treatment including at least surgery or radiotherapy, and at least 2-year disease-free survival were included. Thirty-eight patients (22 men, 16 women) matched the inclusion criteria. RESULTS Thirty seven (97%) reported esthetic and functional improvements in their RIF and volumetric defect at follow-up of 32 months. Major improvement in esthetic and functional outcome was reported by 24 (63%) patients and surgeons and minor by 13 patients and surgeons (34%) without causing any complications. Lipotransfer was also found to significantly improve patient's psychological health postoperatively as showed by significant improvements in Derriford Appearance Scale (DAS24), Short Form Health Survey (SF-36), and University of Washington Quality of Life Questionnaire (UW-QOL V4) scores (P

BACKGROUND The aim of this study was to investigate how common temporomandibular disorder (TMD) symptoms are among head and neck cancer (HNC) patients before and after oncological treatment. METHODS Eighty-nine patients with HNC receiving radiotherapy were enrolled in the study. Patients were examined before radiotherapy and at 6 and 12 months after radiotherapy to evaluate the function and tenderness of the temporomandibular jaw and the muscles of mastication as well as the patient-reported symptoms. RESULTS At 6 months after radiotherapy, there was a large increase in the number of patients reporting problems with opening their mouth, fatigue, stiffness, and pain of the jaw. Sixty-eight percent of the patients had symptoms of TMD before oncological treatment and 94% and 81% had symptoms at the 6- and 12-month follow-up, respectively. CONCLUSION The signs and symptoms of TMD escalate after radiotherapy, with symptoms peaking at 6 months after radiotherapy. Most commonly, patients suffer from restricted mouth opening, stiffness, fatigue, and pain of the jaw.

Background Radiotherapy (RT) is currently considered the treatment of choice for presumed canine intracranial gliomas. However, variable therapeutic responses are described, due to heterogeneous populations and different radiation methods or protocols. Only one study dedicated to intracranial suspected glioma highlighted prognostic criteria. Determination or confirmation of specific clinical and imaging prognostic factors may guide the therapeutic management of these tumours. The objectives were to provide data on long-term clinical outcome (including quality of life, QoL) and to determine specific prognostic factors associated with survival time. We report a single-institution retrospective study, including all dogs with suspected symptomatic primary solitary intracranial glioma, treated with a complete uniform fractionated megavoltage radiation protocol of 15x3Gy over 5 weeks, between January 2013 and February 2019. Thirty-eight client-owned dogs were included. Medical records were retrospectively evaluated for median overall survival time (MST), clinical and imaging responses. Prognostic factors on survival were researched in terms of signalment, clinical presentation, tumour imaging characteristics and response following RT. Finally, the RT’s impact on the dogs’ clinical signs and Qol were evaluated by the owners. Results The disease-specific MST was 698 days (95% CI: 598–1135). Survival at 1 and 2 years were respectively 74.2 ± 7.4% and 49.0 ± 9.8%. Initial clinical signs were related to survival, as well as tumour characteristics such as cystic-pattern, mass effect and Tumour/Brain volume ratio. No significant adverse effect or radiotoxicity was observed. Conclusions RT appears as a safe and effective treatment for canine intracranial gliomas, allowing long-term tumour control, improvement of life’s quality and management of associated clinical signs. The initial clinical signs and MRI characteristics (Tumour/Brain volume ratio, cyst-like lesion and mass effect) may help predict the prognosis.

Animal models of total-body irradiation (TBI) are used to elucidate normal tissue damage and evaluate the efficacy of medical countermeasures (MCM). The accuracy of these TBI models depends on the reproducibility of the radiation dose-response relationship for lethality, which in turn is highly dependent on robust radiation physics and dosimetry. However, the precise levels of radiation each organ absorbs can change dramatically when different photon beam qualities are used, due to the interplay between their penetration and the natural variation of animal sizes and geometries. In this study, we evaluate the effect of varying the radiation energy, namely cobalt-60 (Co-60); of similar penetration to a 4-MV polyenergetic beam), 6 MV and 15 MV, in the absorbed dose delivered by TBI to individual organs of eight Göttingen minipigs of varying weights (10.3-24.1 kg) and dimensions (17.5-25 cm width). The main organs, i.e. heart, lungs, esophagus, stomach, bowels, liver, kidneys and bladder, were contoured by an experienced radiation oncologist, and the volumetric radiation dose distribution was calculated using a commercial treatment planning system commissioned and validated for Co-60, 6-MV and 15-MV teletherapy units. The dose is normalized to the intended prescription at midline in the abdomen. For each animal and each energy, the body and organ dose volume histograms (DVHs) were computed. The results show that more penetrating photon energies produce dose distributions that are systematically and consistently more homogeneous and more uniform, both within individual organs and between different organs, across all animals. Thoracic organs (lungs, heart) received higher dose than prescribed while pelvic organs (bowel, bladder) received less dose than prescribed, due to smaller and wider separations, respectively. While these trends were slightly more pronounced in the smallest animals (10.3 kg, 19 cm abdominal width) and largest animals (20 kg, ∼25 cm abdominal width), they were observed in all animals, including those in the 9-15 kg range typically used in MCM models. Some organs received an average absorbed dose representing80% of prescribed dose when Co-60 was used, whereas all organs received average doses of87% and93% when 6 and 15 MV were used, respectively. Similarly, average dose to the thoracic organs reached as high as 125% of the intended dose with Co-60, compared to 115% for 15 MV. These results indicate that Co-60 consistently produces less uniform dose distributions in the Göttingen minipig compared to 6 and 15 MV. Moreover, heterogeneity of dose distributions for Co-60 is accentuated by anatomical and geometrical variations across various animals, leading to different absorbed dose delivered to organs for different animals. This difference in absorbed radiation organ doses, likely caused by the lower penetration of Co-60 and 6 MV compared to 15 MV, could potentially lead to different biological outcomes. While the link between the dose distribution and variation of biological outcome in the Göttingen minipig has never been explicitly studied, more pronounced dose heterogeneity within and between organs treated with Co-60 teletherapy units represents an additional confounding factor which can be easily mitigated by using a more penetrating energy.

Background Studies have revealed that salvage surgery after definitive chemoradiotherapy (CRT) for unresectable advanced non-small cell lung cancer improves survival with acceptable surgical adverse events. Few reports exist regarding pneumonectomy or the bronchoplastic procedure in this setting. Methods Between 2008 and 2018, 27 patients (21 men; median age, 61 years) underwent salvage surgery after definitive CRT for non-small cell lung cancer. We investigated postoperative short- and long-term outcomes of salvage surgery and aimed to elucidate the feasibility of pneumonectomy or the bronchoplastic procedure. Results The median radiation dose was 60 Gy. The median period from the last day for irradiation to the operative day was 8.5 months. Pneumonectomy was performed in 9 patients, including 2 carinal resections; lobectomy was performed in 18 patients, including 5 bronchoplasties. Bronchial wrapping was performed in 9 cases (33%), R0 resection was achieved in 24 (89%), and postoperative complications were detected in 16 (59%). Although bronchopleural fistulas were found in only 2 patients who underwent pneumonectomy, arrhythmia was observed more frequently in patients who underwent the bronchoplastic procedure (P = .05). Regarding major complications, no relationship with any factors were found. The 90-day mortality was 0%. The 5-year overall and recurrence-free survival were 63% and 27%, respectively. R0 resection was a good prognostic factor for recurrence-free survival (P = .001). Conclusions Perioperative short- and long-term outcomes of salvage surgery after definitive CRT for non-small cell lung cancer were acceptable. Complete resection offered a better recurrence-free survival. The bronchoplastic procedure or pneumonectomy should be considered as an option even after administration of high-dose CRT.

Background Fatigue is one of the most common and distressing side-effects of breast cancer radiotherapy. According to current guidelines, accelerated partial breast irradiation (APBI) may be considered as an alternative treatment option for women with early-stage low-risk breast cancer. One method for APBI is single-dose intraoperative radiotherapy (IORT) applied directly to the tumor bed during breast conserving surgery (BCS). The COSMOPOLITAN trial therefore aims to analyze the intensity of fatigue following single-shot IORT with electrons (IOERT) compared to conventional hypofractionated whole breast irradiation (WBI) in low risk early breast cancer patients. Methods This trial is conducted as a multicenter, prospective, randomized, two-arm phase II study comparing the intensity of fatigue in early-stage breast cancer (cT1cN0cM0, tumor size 50 years) treated either with WBI or APBI after BCS. Secondary outcomes investigated are tumor control, overall survival (OS), disease-free survival (DFS), acute and chronic toxicity, quality of life (QoL) and cosmesis. A total of 202 patients will be randomized into two arms: Patients in arm A will receive WBI (40.05 Gy, 15 fractions) after surgical resection, while patients in arm B will receive IOERT (21 Gy to the 90%-isodose) during BCS. Fatigue will be assessed 12 weeks post surgery with the help of the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale. Discussion The present trial aims to evaluate treatment response to compare single-shot intraoperative electron APBI to conventional WBI following BCS in early-stage low risk breast cancer patients. Fatigue is selected as the primary, patient-reported endpoint due its major clinical relevance. Trial registration The study is prospectively registered on February 12th, 2019: Clinicaltrials.gov, NCT03838419. “Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer (COSMOPOLITAN)”. Study status Ongoing study. Start of recruitment was December 2019.

PURPOSE: Merkel cell carcinoma is highly sensitive to both radiation and immunotherapy. Moreover, concurrent radioimmunotherapy may capitalize on anti-tumor immune activity and improve Merkel cell treatment response, although an enhanced immune system may cross-react with native tissues and lead to significant sequelae. METHODS: Here we present a case study of a patient with metastatic Merkel cell carcinoma treated with radiotherapy concurrent with pembrolizumab. RESULTS: After radioimmunotherapy, he developed sensory neuropathy, visual hallucinations, and mixed motor neuron findings. Neurologic dysfunction progressed to profound gastrointestinal dysmotility necessitating parenteral nutrition and intubation with eventual expiration. CONCLUSION: This case represents a unique autoimmune paraneoplastic neurologic syndrome, likely specific to neuroendocrine tumors and motivated by concurrent radioimmunotherapy. Recognition of the potential role of radioimmunotherapy may provide an advantage in anticipating these severe sequelae.

In intraoperative electron radiation therapy (IOERT) the energy of the electron beam is selected under the conventional assumption of water-equivalent tissues at the applicator end. However, the treatment field can deviate from the theoretic flat irradiation surface, thus altering dose profiles. This patient-based study explored the feasibility of acquiring intraoperative computed tomography (CT) studies for calculating three-dimensional dose distributions with two factors not included in the conventional assumption, namely the air gap from the applicator end to the irradiation surface and tissue heterogeneity. In addition, dose distributions under the conventional assumption and from preoperative CT studies (both also updated with intraoperative data) were calculated to explore whether there are other alternatives to intraoperative CT studies that can provide similar dose distributions. The IOERT protocol was modified to incorporate the acquisition of intraoperative CT studies before radiation delivery in six patients. Three studies were not valid to calculate dose distributions due to the presence of metal artefacts. For the remaining three cases, the average gamma pass rates between the doses calculated from intraoperative CT studies and those obtained assuming water-equivalent tissues or from preoperative CT studies were 73.4% and 74.0% respectively. The agreement increased when the air gap was included in the conventional assumption (98.1%) or in the preoperative CT images (98.4%). Therefore, this factor was the one mostly influencing the dose distributions of this study. Our experience has shown that intraoperative CT studies are not recommended when the procedure includes the use of shielding discs or surgical retractors unless metal artefacts are removed. IOERT dose distributions calculated under the conventional assumption or from preoperative CT studies may be inaccurate unless the air gap (which depends on the surface irregularities of the irradiated volume and on the applicator pose) is included in the calculations. This study was supported by Ministerio de Ciencia, Innovacion y Universidades (http://www.ciencia.gob.es) [grant number TEC2013–48251-C2 to JP, VG-V and MJL-C], co-funded by European Regional Development Fund (ERDF), “A way of making Europe” (https://ec.europa.eu/regional_policy/en/funding/erdf); by Ministerio de Ciencia, Innovacion y Universidades (http://www.ciencia.gob.es), Instituto de Salud Carlos III (https://www.isciii.es) [grant numbers DTS14/00192 to JP, VG-V and FAC; PI15/02121 to FAC and JC-H; PI18/01625 to JP], co-funded by European Regional Development Fund (ERDF), “A way of making Europe” (https://ec.europa.eu/regional_policy/en/funding/erdf); and by Comunidad de Madrid (http://www.comunidad.madrid) [grant number TOPUS-CM S2013/ MIT3024 to JP], co-funded by European Structural and Investment Fund (https://ec.europa.eu/info/funding-tenders/funding-opportunities/fundingprogrammes/overview-funding-programmes_en). The CNIC is supported by the Ministerio de Ciencia, Innovacion y Universidades (http://www.ciencia.gob.es) and the Pro CNIC Foundation (https://www.fundacionprocnic.es) [to MD], and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Sí

Conventional radiotherapy is mainly applied by linear accelerators. Although linear accelerators provide dual (electron/photon) radiation beam modalities, both of them are intrinsically produced by a megavoltage electron current. Modern radiotherapy treatment techniques are based on suitable devices inserted or attached to conventional linear accelerators. Thus, precise control of delivered beam becomes a main key issue. This work presents an integral description of electron beam deflection control as required for novel radiotherapy technique based on convergent photon beam production. Theoretical and Monte Carlo approaches were initially used for designing and optimizing device´s components. Then, dedicated instrumentation was developed for experimental verification of electron beam deflection due to the designed magnets. Both Monte Carlo simulations and experimental results support the reliability of electrodynamics models used to predict megavoltage electron beam control.

This is a retrospective dose-volume-outcome analysis of radiation-induced nasopharyngeal ulcers after intensity modulated radiotherapy in primary nasopharyngeal carcinoma (NPC) patients, with the aim to determine how the radiation doses to nasopharynx influence the occurence of radiation-induced nasopharyngeal ulcer (RINU) and predict the most serious complication of radiotherapy for NPC.Data from 6023 consecutive and nonselected histologically proven primary NPC patients treated with definitive IMRT were collected and 25 patients were diagnosed with nasopharyngeal ulcer and met the diagnosis criteria of RINU. Predictive dosimetric factors were identified by using univariate and multivariate analysis.Paired samples t-tests showed all dosimetric factors were significantly correlated with the development of RINU, and these factors were associated with each other closely. (P 0.001) Multivariate analysis revealed D3cc (dose to 3 mL of the nasopharynx) was an independent predictor for RINU (P = 0.01); the area under the ROC curve for D3cc was 0.87 (P 0.001), and the cutoff point 73.67 Gy may be the dose tolerance of the nasopharynx. The primary tumor location, distribution of high dose regions and the location of RINU were consistent.The study indicates that radiation-induced nasopharyngeal ulcer is consistent with primary tumor location and 'hottest spots' regions and we suggest a D3cc limit of 73.67 Gy for the nasopharynx. Physicians should be cautious of such 'hot spots' in the nasopharynxduring IMRT treatment plan optimization, review and approval to avoid the most serious complication of radiotherapy for NPC.

AAPM Report 142 recommends and the State of Ohio requires that the imaging dose be quantified in radiotherapy applications. Using the TG51 dose calibration protocol for MV Imaging dose measurement requires knowledge of the kQ parameter for the beam quality and the ionization chamber type under investigation. The %dd(10)x of the Varian TrueBeam 2.5 MV imaging beam falls outside the range of the available data for the calculation of the kQ value. Due to the similarities of the 2.5 MV imaging beam and the 60Co beam, we and others made the assumption that kQ = 1.0 in TG51 calculations. In this study, we used the TG21 and TG51 calibration protocols in conjunction to validate that kQ = 1.0 for the 2.5 MV imaging beam using a PTW 30013 farmer chamber. Standard measurements for TG51 absolute dosimetry QA were performed at 100 cm SSD, 10 cm depth, 10 × 10 field size, delivering 100 Monitor Units to a waterproof Farmer Chamber (PTW TN30013) for both 2.5 and 6 MV. Both the TG21 and TG51 formalisms were used to calculate the dose to water per MU at dmax (Dw/MU) for the 6 MV beam. The calculated outputs were 1.0005 and 1.0004 cGy/MU respectively. The TG21 formalism was then used to calculate (Dw/MU) for the 2.5 MV imaging beam. This value was then used in the TG51 formalism to find kQ for the 2.5 MV imaging beam. A kQ value of 1.00 ± 0.01 was calculated for 2.5 MV using this method.

A comprehensive evaluation of the current national and regional radiotherapy capacity in Austria with an estimation of demands for 2020 and 2030 was performed by the Austrian Society for Radiation Oncology, Radiobiology and Medical Radiophysics (OGRO). All Austrian centers provided data on the number of megavoltage (MV) units, treatment series, fractions, percentage of retreatments and complex treatment techniques as well as the daily operating hours for the year 2014. In addition, waiting times until the beginning of radiotherapy were prospectively recorded over the first quarter of 2015. National and international epidemiological prediction data were used to estimate future demands. For a population of 8.51 million, 43 MV units were at disposal. In 14 radiooncological centers, a total of 19,940 series with a mean number of 464 patients per MV unit/year and a mean fraction number of 20 (range 16–24) per case were recorded. The average re-irradiation ratio was 14%. The survey on waiting times until start of treatment showed provision shortages in 40% of centers with a mean waiting time of 13.6 days (range 0.5–29.3 days) and a mean maximum waiting time of 98.2 days. Of all centers, 21% had no or only a limited ability to deliver complex treatment techniques. Predictions for 2020 and 2030 indicate an increased need in the overall number of MV units to a total of 63 and 71, respectively. This OGRO survey revealed major regional differences in radiooncological capacity. Considering epidemiological developments, an aggravation of the situation can be expected shortly. This analysis serves as a basis for improved public regional health care planning.

The aim of this test study is to check whether boron nitride (BN) might be applied as a detector material in high-energy photon-beam dosimetry. Boron nitride exists in various crystalline forms. Hexagonal boron nitride (h-BN) possesses high mobility of the electrons and holes as well as a high volume resistivity, so that ionizing radiation in the clinical range of the dose rate can be expected to produce a measurable electrical current at low background current. Due to the low atomic numbers of its constituents, its density (2.0 g cm−3) similar to silicon and its commercial availability, h-BN appears as possibly suitable for the dosimetry of ionizing radiation. Five h-BN plates were contacted to triaxial cables, and the detector current was measured in a solid-state ionization chamber circuit at an applied voltage of 50 V. Basic dosimetric properties such as formation by pre-irradiation, sensitivity, reproducibility, linearity and temporal resolution were measured with 6 MV photon irradiation. Depth dose curves at quadratic field sizes of 10 cm and 40 cm were measured and compared to ionization chamber measurements. After a pre-irradiation with 6 Gy, the devices show a stable current signal at a given dose rate. The current–voltage characteristic up to 400 V shows an increase in the collection efficiency with the voltage. The time-resolved detector current behavior during beam interrupts is comparable to diamond material, and the background current is negligible. The measured percentage depth dose curves at 10 cm × 10 cm field size agreed with the results of ionization chamber measurements within ±2%. This is a first study of boron nitride as a detector material for high-energy photon radiation. By current measurements on solid ionization chambers made from boron nitride chips we could demonstrate that boron nitride is in principle suitable as a detector material for high-energy photon-beam dosimetry.

High energy radiotherapy can produce contaminant neutrons through the photonuclear effect. Patients receiving external beam radiation therapy to the pelvis may have high‐density hip prostheses. Metallic materials such as those in hip prostheses, often have high cross‐sections for neutron interaction. In this study, Thackray (UK) prosthetic hips have been irradiated by 18 MV radiotherapy beams to evaluate the additional dose to patients from the activation products. Hips were irradiated in‐ and out‐of field at various distances from the beam isocenter to assess activation caused in‐field by photo‐activation, and neutron activation which occurs both in and out‐of‐field. NaI(Tl) scintillator detectors were used to measure the subsequent gamma‐ray emissions and their half‐lives. High sensitivity Mg, Cu, P doped LiF thermoluminescence dosimeter chips (TLD‐100H) were used to measure the subsequent dose at the surface of a prosthesis over the 12 h following an in‐field irradiation of 10,000 MU to a hip prosthesis located at the beam isocenter in a water phantom. 53Fe, 56Mn, and 52V were identified within the hip following irradiation by radiotherapy beams. The dose measured at the surface of a prosthesis following irradiation in a water phantom was 0.20 mGy over 12 h. The dose at the surface of prostheses irradiated to 200 MU was below the limit of detection (0.05 mGy) of the TLD100H. Prosthetic hips are activated by incident photons and neutrons in high energy radiotherapy, however, the dose resulting from activation is very small.

To estimate the long-term risk of second malignancies after breast cancer treatment in a large homogeneous cohort from a single institution.All patients in this study were treated for non-metastatic breast cancer at the Curie institute, Paris, between 1981 and 2000. We calculated the cumulative incidence of second malignancies and the risk of developing each type of second malignancies over a period of 10 to 15 years. The observed crude incidence rates in the entire patient population were then compared to the expected incidence in the general population of French women, as provided by age-standardized data. A standardized incidence ratio (SIR) was calculated for all second malignancies. We also calculated second malignancies standardized incidence ratios for patients who underwent adjuvant therapy for breast cancer.The study cohort included a total of 17,745 women. The median follow-up since diagnosis was 13.4 years (range: 2-29 years). The 15-year cumulative incidence of second malignancies was 1.807 per 100,000 (CI 1.729-1.884). A total of 2370 second malignancies were observed during follow-up, 2010 in the radiotherapy arm and 360 in the no radiotherapy arm (relative risk [RR] 1.15 [1.03-1.28], P=0.0134). Crude incidence rates were significantly higher in our cohort than in the general population for contralateral breast cancer (SIR 2.96 [confidence interval (CI) 2.82-3.12], P0.0001), sarcomas (SIR 8.48 [CI 6.41-11.22], P0.0001), leukaemia (SIR 2.37 [CI 1.85-3.04], P0.0001), lung cancer (SIR 1.39 [CI 1.13-1.72], P0.0022) and gynaecological cancer (SIR 1.31 [CI 1.15-1.50], P=0.0001). Among patients treated for breast cancer, those who received radiotherapy was associated with an excess risk of sarcoma as compared to those have not had (RR 5.59 [CI 1.35-23.17], P0.001).Women treated for breast cancer had a significantly increased risk of several kinds of second malignancies compared to the general population.

Melanoma is mainly treated by surgery and rarely with radiation because of the high radioresistance of this tumor. Nevertheless, radiotherapy is the preferred treatment modality for unresectable lesions and avoiding cosmetic disfigurement caused by surgical excision. This study investigated the therapeutic advantage of gold nanoparticles (AuNPs) for kilovoltage X-ray treatment of melanoma.Commercial AuNPs were evaluated for cytotoxicity and cellular internalization. The sensitivity of human skin melanoma cells to 150 and 450 kVp X-ray exposure was assessed in terms of clonogenicity with or without spherical AuNP treatment.AuNP treatment elicited dose enhancement effect on melanoma cells exposed to kilovoltage X-rays. Treatment with 320 μM 50 nm AuNPs before exposure to 150 kVp X-rays at 2 Gy resulted in clonogenic cell death equivalent to that caused by 4.3 Gy X-rays without AuNP treatment.AuNPs of 50 nm in size can regulate melanoma cells in kilovoltage X-ray treatment by functioning as dose-enhancement agent and thus improving radioresponse of the cells. Melanomas of stages T1-T3 gain therapeutic benefits from 150 kVp X-ray treatment.

Background and purpose: Aside from the enhancement of physical dose deposited by antiprotons annihilating in tissue-like material compared to protons of the same range a further increase of biological effective dose has been demonstrated. This enhancement can be expressed in an increase of the relative biological effectiveness (RBE) of antiprotons near the end of range. We have performed the first-ever direct measurement of the RBE of antiprotons both at rest and in flight.Materials and methods: Experimental data were generated on the RBE of an antiproton beam entering a tissue-like target consisting of V79 cells embedded in gelatin with an energy providing a range of approximately 10 cm.Results: The RBE in the entrance channel (the "plateau") is only slightly above the value for a comparable proton beam, and remains low until the proximal edge of the spread-out Bragg peak (SOBP). A steep increase of RBE is seen starting from the onset of the SOBP.Conclusions: This paper reports the final results of the experiment AD-4/ACE at CERN on the first-ever direct measurement of RBE of antiprotons and constitutes the first step toward developing treatment plans. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Monitoring of high-energy photon dose in radiation therapy is crucial for radiation protection, as well as to estimate the radiation effects in the operating microelectronic devices. The aim of this work was to investigate the possibility of using the photoactivation technique to monitor the high-energy photon fluence in the Varian 21EX 23MV CLINAC. The 52Cr(γ,n)51Cr and 66Zn(γ,n)65Zn reactions were used. It was found that 51Cr and 65Zn can be used successfully to monitor the fluence for short term (80 days) and long term (110 days), respectively.

Purpose: Current techniques and procedures for dosimetry in microbeams typically rely on radiochromic film or small volume ionization chambers for validation and quality assurance in 2D and 1D, respectively. Whilst well characterized for clinical and preclinical radiotherapy, these methods are noninstantaneous and do not provide real time profile information. The objective of this work is to determine the suitability of the newly developed vM1212 detector, a pixelated CMOS (complementary metal-oxide-semiconductor) imaging sensor, for in situ and in vivo verification of x-ray microbeams. Methods: Experiments were carried out on the vM1212 detector using a 220 kVp small animal radiation research platform (SARRP) at the Helmholtz Centre Munich. A 3 x 3 cm2 square piece of EBT3 film was placed on top of a marked nonfibrous card overlaying the sensitive silicon of the sensor. One centimemter of water equivalent bolus material was placed on top of the film for build-up. The response of the detector was compared to an Epson Expression 10000XL flatbed scanner using FilmQA Pro with triple channel dosimetry. This was also compared to a separate exposure using 450µm of silicon as a surrogate for the detector and a Zeiss Axio Imager 2 microscope using an optical microscopy method of dosimetry. Microbeam collimator slits with range of nominal widths of 25, 50, 75, and 100µm were used to compare beam profiles and determine sensitivity of the detector and both film measurements to different microbeams. Results: The detector was able to measure peak and valley profiles in real-time, a significant reduction from the 24hr self-development required by the EBT3 film. Observed full width at half maximum (FWHM) values were larger than the nominal slit widths, ranging from 130 to 190µm due to divergence. Agreement between the methods was found for peak-to-valley dose ratio (PVDR), peak to peak separation and FWHM, but a difference in relative intensity of the microbeams was observed between the detectors. Conclusions: The investigation demonstrated that pixelated CMOS sensors could be applied to microbeam radiotherapy for real-time dosimetry in the future, however the relatively large pixel pitch of the vM1212 detector limit the immediate application of the results.

Background Extraskeletal osteosarcoma is an extremely rare disease, comprising less than 0.1% of all cancers diagnosed in the United States, of which less than 5% occur in the upper extremities. The management of two cases of pediatric upper extremity extraskeletal osteosarcoma is discussed. Case description Two children initially noticed painless left upper extremity masses at the ages of 16 and 13, respectively. Following a period of several months, both lesions became symptomatic, necessitating operative intervention, which revealed giant cell-rich extraskeletal osteosarcoma; PET staging following gross total resection revealed no residual or metastatic disease in either patient. After extensive discussion with the patients and family, adjuvant chemotherapy was initiated for one patient, and adjuvant radiation therapy was initiated in both patients. Conclusions Despite the rarity of these tumors, the importance of radiation therapy has been established by current and ongoing studies such as the Children's Oncology Group study ARST0332. Radiation therapy remains an important component of the multimodality therapy comprising optimal treatment of this disease, despite the relative paucity of long-term outcome data derived from level I evidence.

Nowadays, high-energy X-rays produced by medical linear accelerators (LINACs) are widely used in many Radiation Therapy (RT) centers. High-energy photons (> 8 MeV) produce undesired neutrons in the LINAC head which raise concerns about unwanted neutron dose to the patients and RT personnel. Regarding the significance of radiation protection in RT, it is important to evaluate photoneutron contamination inside the RT room. Unfortunately, neutron dosimeters used for this purpose have limitations that can under the best conditions cause to > 10% uncertainty. In addition to this uncertainty, the present Monte Carlo (MC) study introduces another uncertainty in measurements (nearly up to 20%) when neutron ambient dose equivalent ( H n * (10)) is measured at the patient table or inside the maze and the change in neutron energy is ignored. This type of uncertainty can even reach 35% if H n * (10) is measured by dosimeters covered by a layer of 10B as converter. So, in these cases, neglecting the change in neutron energy can threaten the credibility of measured data and one should attend to this energy change in order to reduce measurement uncertainty to the possible minimum. This study also discusses the change in neutron spectra and H n * (10) at the patient table caused by removing a typical RT room from MC simulations. Under such conditions, neutron mean energy ( Ē n ) overestimated by 0.2–0.4 MeV at the patient table. Neutron fluence ( φ n ) at the isocenter (IC) was underestimated by 23–54% for different field sizes that caused H n * (10) to be miscalculated up to 24%. This finding informs researchers that for accurate evaluation of H n * (10) at the patient table, simulating the RT room is an effective parameter in MC studies.

The aim of this study is to investigate the dosimetric uncertainty of stochastic noise and the post-irradiation density growth for reflective-type radiochromic film to obtain the appropriate dose from the exactly controlled film density. Film pieces were irradiated with 6-MV photon beams ranging from 0 to 400 cGy. The pixel values (PVs) of these films were obtained using a flatbed scanner at elapsed times of 1 min to 120 h between the end of irradiation and the film scan. The means and standard deviations (SDs) of the PVs were calculated. The SDs of the converted dose scale, usd, and the dose increases resulting from the PV increases per ±29 min at each elapsed time, utime, were computed. The combined dose uncertainties from these two factors, uc, were then calculated. A sharp increase in the PV occurred within the first 3 h after irradiation, and a slight increase continued from 3 h to 120 h. usd was independent of post-irradiation elapsed time. Sharp decreases in utime were obtained within 1 h after irradiation, and slight decreases in utime were observed from 1 to 24 h after irradiation. uc first decreased 1 h after irradiation and remained constant afterward. Assuming that the post-irradiation elapsed times of all of the related measurements are synchronized within ±29 min, the elapsed time should be at least 1 h in our system. It is important to optimize the scanning protocol for each institution with consideration of the required measurement uncertainty and acceptable latency time.

Purpose Online verification and 3D dose reconstruction on daily patient anatomy have the potential to improve treatment delivery, accuracy and safety. One possible implementation is to recalculate dose based on online fluence measurements with a transmission detector (TD) attached to the linac. This study provides a detailed analysis of the influence of a new TD on treatment beam characteristics. Methods The influence of the new TD on surface dose was evaluated by measurements with an Advanced Markus Chamber (Adv-MC) in the build-up region. Based on Monte Carlo simulations, correction factors were determined to scale down the over-response of the Adv-MC close to the surface. To analyze the effects beyond d max percentage depth dose (PDD), lateral profiles and transmission measurements were performed. All measurements were carried out for various field sizes and different SSDs. Additionally, 5 IMRT-plans (head & neck, prostate, thorax) and 2 manually created test cases (3 × 3 cm 2 fields with different dose levels, sweeping gap) were measured to investigate the influence of the TD on clinical treatment plans. To investigate the performance of the TD, dose linearity as well as dose rate dependency measurements were performed. Results With the TD inside the beam an increase in surface dose was observed depending on SSD and field size (maximum of +11%, SSD = 80 cm, field size = 30 × 30 cm 2 ). Beyond d max the influence of the TD on PDDs was below 1%. The measurements showed that the transmission factor depends slightly on the field size (0.893-0.921 for 5 × 5 cm 2 to 30 × 30 cm 2 ). However, the evaluation of clinical IMRT-plans measured with and without the TD showed good agreement after using a single transmission factor (γ (2%/2mm) > 97%, δ ±3% >95%). Furthermore, the response of TD was found to be linear and dose rate independent (maximum difference Conclusions When placed in the path of the beam, the TD introduced a slight, clinically acceptable increase of the skin dose even for larger field sizes and smaller SSDs and the influence of the detector on the dose beyond d max as well as on clinical IMRT-plans was negligible. Since there was no dose rate dependency and the response was linear, the device is therefore suitable for clinical use. Only its absorption has to be compensated during treatment planning, either by the use of a single transmission factor or by including the TD in the incident beam model.

Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly focused synchrotron beam into arrays of parallel microbeams, typically a few tens of microns wide and depositing several hundred grays. This irradiation modality was shown to have a high therapeutic impact on tumors, especially in intracranial locations. However, mechanisms responsible for such a property are not fully understood.Thanks to recent progress in dosimetry, we compared the effect of MRT and synchrotron broad beam (BB) radiation therapy delivered at comparable doses (equivalent to MRT valley dose) on tumor growth control and on classical radiobiological functions by histologic evaluation and/or transcriptomic analysis.MRT significantly improved survival of rats bearing 9L intracranial glioma compared with BB radiation therapy delivered at a comparable dose (P.001); the efficacy of MRT and BB radiation therapy was similar when the MRT dose was half that of BB. The greater efficacy of MRT was not correlated with a difference in cell proliferation (Mki67 and proliferating cell nuclear antigen) or in transcriptomic stimulation of angiogenesis (vascular endothelial growth factor A or tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2) but was correlated with a higher cell death rate (factor for apoptosis signals) and higher recruitment of macrophages (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and CD68 transcripts) a few days after MRT.These results show the superiority of MRT over BB radiation therapy when applied at comparable doses, suggesting that spatial fractionation is responsible for a specific and particularly efficient tissue response. The higher induction of cell death and immune cell activation in brain tumors treated by MRT may be involved in such responses.

In a radiotherapy facility, safety in areas next to the treatment room can be of concern when irradiating downward due to oblique x-ray transmission through the floor and/or walls, especially in areas immediately adjacent or underground. Even when there is no basement underneath, a usual conservative solution is to build a thick concrete slab as the base for the treatment room. Of course, this implies deeper soil excavation and higher associated costs. As a convenient alternative, the limiting walls can be buried a certain depth below floor level to shield oblique, downward irradiation. Besides, for space considerations, laminated barriers are usually employed, and some additional shielding to the floor may be required (L-shaped barriers). In this work, the author introduces an analytical method for calculating the required wall penetration below floor level or, alternatively, the additional floor shielding for L-shaped barriers, taking into account in either case the attenuation properties of the earth underneath the vault. Interestingly, the required penetration depth for a given wall barrier (primary or secondary), relative to a reference thickness, is only a function of basic attenuation data. Likewise, for a laminated, lead-concrete barrier, the required dimensions depend on the relative amount of lead used for the wall and on the corresponding attenuation data. The shielding design criteria developed in this work to protect underground nearby sites is conservative in nature, yet it yields optimal shield dimensions for wall footing and for wall-floor shielding, avoiding the need to construct oversized concrete slab floors.

The present study compares in silico treatment plans using hybrid plan technique during hypofractionated radiation of mammary carcinoma with simultaneous integrated boost (SIB). The influence of 6 MV photon radiation in flattening filter free (FFF) mode against the clinical standard flattening filter (FF) mode is to be examined. RT planning took place with FF and FFF radiation plans for 10 left-sided breast cancer patients. Hybrid plans were realised with two tangential IMRT fields and one VMAT field. The dose prescription was in line with the guidelines in the ARO-2010-01 study. The dosimetric verification took place with a manufacturer-independent measurement system. Required dose prescriptions for the planning target volumes (PTV) were achieved for both groups. The average dose values of the ipsi- and contralateral lung and the heart did not differ significantly. The overall average incidental dose to the left anterior descending artery (LAD) of 8.24 ± 3.9 Gy in the FFF group and 9.05 ± 3.7 Gy in the FF group (p

The ion recombination correction factor (ks) is determined for the Advanced Markus chamber exposed to electron beams produced by a dedicated intraoperative radiation therapy (IORT) accelerator at medium dose-per-pulse values. The authors evaluate five different methods. Three of them are known as Boag's modified expressions, which are based on the two-voltage-analysis method and include the free-electron component. In the fourth method the IAEA TRS-398 protocol is applied, which uses the same two-voltage-analysis method but ignores the free-electron component, and finally the fifth approach is known as the Jaffé plot. ks values were obtained in the range of 4 mGy/pulse to 42 mGy/pulse and were compared with ks values determined by means of radiochromic films, which are independent of the dose rate. It was found that ks values that resulted from the three Boag's modified expressions and the TRS-398 protocol deviated by on average 1.5% and 1.4%, respectively, from the reference ks values based on film dosimetry. These results are within the estimated relative uncertainty of ±3%. On the other hand, the absolute deviation of each method depends on the dose-per-pulse value at which the method is investigated. In conclusion, in the medium dose-per-pulse range all Boag's modified expressions could be used for ks determination. Above a dose-per-pulse value of 35 mGy/pulse, the TRS-398 approach should be avoided. At 27 mGy/pulse and a maximum operation voltage of 300 V the ks value resulting from the Jaffé plot showed a 0.3% deviation from the reference value. More investigation on the Jaffé plot is necessary at higher dose-per-pulse values.

To evaluate the effects of rectal enemas on rectal doses during postoperative high-dose-rate (HDR) vaginal cuff brachytherapy (VCB). This prospective trial included 59 patients. Two rectal cleansing enemas were self-administered before the second fraction, and fraction 1 was considered the basal status. Dose–volume histogram (DVH) values were generated for the rectum and correlated with rectal volume variation. Statistical analyses used paired and unpaired t-tests. Despite a significant 15 % reduction in mean rectal volume (44.07 vs. 52.15 cc, p = 0.0018), 35.6 % of patients had larger rectums after rectal enemas. No significant rectal enema-related DVH differences were observed compared to the basal data. Although not statistically significant, rectal cleansing-associated increases in mean rectal DVH values were observed: D0.1 cc: 6.6 vs. 7.21 Gy; D1 cc: 5.35 vs. 5.52 Gy; D2 cc: 4.67 vs. 4.72 Gy, before and after rectal cleaning, respectively (where Dx cc is the dose to the most exposed x cm3). No differences were observed in DVH parameters according to rectal volume increase or decrease after the enema. Patients whose rectal volume increased also had significantly larger DVH parameters, except for D5 %, D25 %, and D50 %. In contrast, in patients whose rectal volume decreased, significance was only seen for D25 % and D50 % (Dx % dose covering x % of the volume). In the latter patients, nonsignificant reductions in D2 cc, D5 cc and V5 Gy (volume receiving at least 5 Gy) were observed. The current rectal enemas protocol was ineffective in significantly modifying rectal DVH parameters for HDR-VCB.

Ratio of percentage depth dose (PDD) at two depths, PDD at a depth of 10 cm (PDD10), and beam flatness are monitored regularly for radiotherapy beams for quality assurance. The purpose of this study is to understand the effects of changes in one of these parameters on the other. Is it possible to monitor only the beam flatness and not PDD? The investigation has two components. Naturally occurring i.e., unintended changes in PDD ratio and in-plane flatness for 6 and 10 MV photon beams for one particular Siemens Artiste Linac are monitored for a period of about 4 years. Secondly, deliberate changes in the beam parameters are induced by changing the bending magnet current (BMI). Relationships between various beam parameters for unintended changes as well as deliberate changes are characterized. Long term unintentional changes of PDD ratio are found to have no systematic trend. The flatness in the inplane direction for 6 and 10 MV beams show slow increase of 0.43 and 0.75% respectively in about 4 years while the changes in the PDD ratio show no such trend. Over 10% changes in BMI are required to induce changes in the beam quality indices at 2% level. PDD ratio for the 10 MV beam is found to be less sensitive, while the depth of maximum dose, d(max), is more sensitive to the changes in BMI compared to the 6 MV beam. Tolerances are more stringent for PDD10 than PDD ratio for the 10 MV beam. PDD ratio, PDD10, and flatness must be monitored independently. Furthermore, off axis ratio alone cannot be used to monitor flatness. The effect of beam quality change in the absolute dose is clinically insignificant.

PurposeTo review the long-term corneal complications after high-dose external beam orbital radiotherapy given to patients for lacrimal gland carcinomas. The impact of prophylactic measures to improve long-term ocular surface health is also assessed.DesignRetrospective case series.ParticipantsPatients under the care of Moorfields Eye Hospital and receiving external beam radiotherapy for primary epithelial lacrimal gland carcinoma between 1975 and 2014.MethodsRetrospective review of ophthalmic case notes at Moorfields Eye Hospital, and oncology and general physician records.Main outcome measuresThe occurrence of corneal perforation, and time to perforation.ResultsSixty-seven patients were included in this study, of whom nine (13%) developed corneal perforation at a median time of 10.4 months after radiotherapy (mean 35; range 3.2 months to 14.5 years); the majority (7/9; 78%) perforated within 36 months of radiotherapy. The mean follow-up interval of the whole cohort was 8.2 years (median 4.6; range, 2 months to 30.7 years).ConclusionsAlthough most patients with globe-sparing treatment of lacrimal gland carcinoma did not suffer corneal perforation, they usually require long-term therapy to maintain the ocular surface. The high-dose external beam radiotherapy needed for lacrimal gland carcinoma can produce significant ocular surface morbidity, and the 13% incidence of corneal perforation was greatest in the first 3 years after irradiation.

Ionization chamber dosimetry is predominantly used for determination of the absorbed dose to water in 60Co and high-energy radiotherapy photon beams. The most widespread ionization chambers employed for absolute or reference dose determinations in reference conditions are the Farmer-type cylindrical ionization chambers. The Farmer-type ionization chambers have a variety of constructions and materials and their responses vary in the radiation beam. Clinical accelerators, in addition to conventional photon beams with flattening-filter, can also deliver flattening-filter-free (FFF) photon beams. The responses of five different Farmer-type cylindrical ionization chambers were experimentally examined with reference to absorbed dose determination in reference conditions when using the International Atomic Energy Agency (IAEA) - American Association of Physicists in Medicine (AAPM) Technical Reports Series no. 483 (TRS-483) and the IAEA TRS-398 dosimetry protocol in the present investigation. The irradiations were performed using 60Co and megavoltage photon beams with 6 MV, 15 MV, 6 MV FFF and 10 MV FFF nominal photon energies. The chamber calibrations were performed at different Secondary Standard Dosimetry Laboratories and are traceable to primary standards at different Primary Standard Dosimetry Laboratories. The chambers were also cross-calibrated at our laboratory using 60Co γ-beam. The variation found in the data regarding the reference dose determination using the various Farmer-type chambers in the photon beams employed was about 1% at maximum. Thus, the selection of the ionization chamber in reference dose determinations may affect the outcomes. The differences in the absorbed dose values were similar in the conventional as well as in the FFF photon beams. For the FFF photon beams the absorbed dose computations were performed using the IAEA-AAPM TRS-483 dosimetry protocol. Two of the ionization chambers used had identical construction but different central electrodes, i.e. graphite versus aluminium. The results obtained using these two chambers show that, in the photon beams examined, the employed correction for the central electrode (p cel ) regarding these two chambers is associated with an inaccuracy which is larger than the calculated uncertainty for this correction. The outcomes found in the present experimental investigation using the various ionization chambers also indicate possible inaccuracy in the employed beam quality correction factors (k Q ) and imply the need for a revision of these factors.

Opinion statement: Anaplastic oligodendroglial tumors have gained increasing interest with the emerging role of molecular markers and systemic chemotherapy during the past years. The long-term results of two landmark trials, RTOG 9402 and EORTC 26961, have resulted in a reconsideration of the appropriate therapeutic approaches for patients with these tumors. Both trials indicate that patients whose tumors harbor a 1p/19q co-deletion benefit particularly from the addition of procarbazine/lomustine (CCNU)/vincristine (PCV) chemotherapy to radiation therapy (RT). The median survival of patients with co-deleted tumors treated within the RTOG trial with PCV before irradiation was 14.7years compared with 7.3years of patients who received RT alone. Median overall survival has not been reached in the RT plus PCV arm of the EORTC trial, but a similar difference can be anticipated after a follow-up of more than 12years. In contrast, no such benefit was observed for patients with tumors lacking 1p/19q co-deletion. Outside clinical trials, patients with anaplastic oligodendroglial tumors, and 1p/19q co-deletion therefore should be offered a combined treatment modality regimen, including radio- and chemotherapy. PCV, however, is associated with significant hematological toxicity and also nonhematological side effects, which probably translate into reduced quality of life for long-term survivors. Therefore, it might be warranted to replace PCV by temozolomide, which displays a more favorable side effect profile. Data from the NOA-04 study suggest that PCV and temozolomide have similar effects. However, long-term data on the benefit from temozolomide are lacking, making a definite answer on the equivalence of temozolomide and PCV in anaplastic oligodendroglioma (AO) impossible. The current evidence precludes RT alone for AO patients. Neither the RTOG nor the EORTC trial defined the role of chemotherapy alone. A comparison of combined modality treatment with chemotherapy alone followed by RT at progression is pending. Long-term follow-up of NOA-04 patients and results from future trials may help to clarify these questions. With more and more AO patients living 10years or more, particular attention must be paid to late side effects, such as neurotoxicity, and careful monitoring is required for all treated patients

Modulated electro-hyperthermia (mEHT) is a form of hyperthermia used in the treatment of cancer. It is a variation that relies on a particular form of enhanced selectivity to enable more effective cancerous cell death yet maintaining the integrity of healthy non-cancerous cells. It is yet to successfully make the major step into the wider medical community despite several encouraging trials. In this study, we investigate mEHT from an in vitro perspective. We demonstrate a supra-additive effect on 9 L gliosarcoma cells when exposed to mEHT in combination with MV X-ray radiation. The supra-additive effect is hypothesized to be induced by the mEHT mechanism that in turn causes apoptosis, membrane damage and an increase in rate of cell growth. This proves to be extremely advantageous in the case of the aggressive 9 L cell line as it is known to be radioresistant. However, the universal success of this multimodal treatment does not appear to be positive for all cell lines and requires further research. Due to the fundamental approach taken in this research, our results also provide a new prospect for mEHT to be a tool for sterilizing otherwise radioresistant cancers.

Currently, lung cancer is one of the most lethal types of cancer (IARC, 2012), the pathology being detected in advanced stage, when the tumor has considerable volume because the disease in most cases asymptomatic in the early stages (INCA, 2016). Dosimetry analysis of healthy organs under real conditions is not feasible. Therefore, computational simulations are used to aid in dose verification in organs of patients submitted to radiotherapy. The goal of this study was to calculate the equivalent dose, due to photons, in the surrounding of healthy organs of patients submitted to radiotherapy for lung cancer, through computational modeling. The simulation was performed using the MCNPX code (MNCPX, 2006), Rex and Regina phantoms (ICRP 110, 2009), radiotherapy room, Siemens Oncor Expression accelerator operating at 6 MV and treatment protocol adopted at the INCA (National Cancer Institute – Brazil). The results obtained, considering the dose due to photons for both phantoms indicate that organs located inside the thoracic cavity received higher dose, being the bronchi, heart and esophagus more affected, due to their anatomical positioning. Clinical data describe the development of bronchiolitis, esophagitis and cardiomyopathies with decreased cardiopulmonary function as one of the major effects of lung cancer treatment. In the Regina phantom, the second largest dose was in the region of the breasts with 615.73 mSv/Gy, while in the Rex the dose was 514.06 mSv/Gy, event related to the difference of anatomical structure of the organ. A qualitative analysis was performed between the dose deposition profile of the treatment planning system and the simulated treatment through the tmesh command and a similar profile of dose distribution was verified throughout the patient's body.

Production of radioisotopes in medical linear accelerators (linacs) is of concern when the beam energy exceeds the threshold for the photonuclear interaction. Staff and patients may receive a radiation dose as a result of the induced radioactivity in the linac. Gamma-ray spectroscopy was used to identify the isotopes produced following the delivery of 18 MV photon beams from a Varian 21EX and an Elekta Synergy. The prominent radioisotopes produced include 187W, 63Zn, 56Mn, 24Na and 28Al in both linac models. The dose rate was measured at the beam exit window (12.6 µSv in the first 10 min) following 18 MV total body irradiation (TBI) beams. For a throughput of 24 TBI patients per year, staff members are estimated to receive an annual dose of up to 750 μSv at the patient location. This can be further reduced to 65 μSv by closing the jaws before re-entering the treatment bunker.

The purpose of this work was to experimentally investigate the out‐of‐field dose in a water phantom, with several high energy electron beams used in external beam radiotherapy (RT). The study was carried out for 6, 9, 12, and 18 MeV electron beams, on three different linear accelerators, each equipped with a specific applicator. Measurements were performed in a water phantom, at different depths, for different applicator sizes, and off‐axis distances up to 70 cm from beam central axis (CAX). Thermoluminescent powder dosimeters (TLD‐700) were used. For given cases, TLD measurements were compared to EBT3 films and parallel‐plane ionization chamber measurements. Also, out‐of‐field doses at 10 cm depth, with and without applicator, were evaluated. With the Siemens applicators, a peak dose appears at about 12–15 cm out of the field edge, at 1 cm depth, for all field sizes and energies. For the Siemens Primus, with a 10×10cm2 applicator, this peak reaches 2.3%, 1%, 0.9% and 1.3% of the maximum central axis dose (Dmax) for 6, 9, 12 and 18 MeV electron beams, respectively. For the Siemens Oncor, with a 10×10cm2 applicator, this peak dose reaches 0.8%, 1%, 1.4%, and 1.6% of Dmax for 6, 9, 12, and 14 MeV, respectively, and these values increase with applicator size. For the Varian 2300C/D, the doses at 12.5 cm out of the field edge are 0.3%, 0.6%, 0.5%, and 1.1% of Dmax for 6, 9, 12, and 18 MeV, respectively, and increase with applicator size. No peak dose is evidenced for the Varian applicator for these energies. In summary, the out‐of‐field dose from electron beams increases with the beam energy and the applicator size, and decreases with the distance from the beam central axis and the depth in water. It also considerably depends on the applicator types. Our results can be of interest for the dose estimations delivered in healthy tissues outside the treatment field for the RT patient, as well as in studies exploring RT long‐term effects. PACS number(s): 87.53.Bn, 87.56.bd, 87.56.J‐

The accurate measurement of the linear accelerator (linac) radiation isocenter is critical, especially for stereotactic treatment. Traditional quality assurance (QA) procedure focuses on the measurement of single radiation isocenter, usually of 6 megavoltage (MV) photon beams. Single radiation isocenter is also commonly assumed in treatment planning systems (TPS). Due to different flattening filters and bending magnet and steering parameters, the radiation isocenter of one energy mode can deviate from another if no special effort was devoted. We present the first experience of the multiradiation isocenters alignment on an Elekta linac, as well as its corresponding QA procedure and clinical impact. An 8 mm ball‐bearing (BB) phantom was placed at the 6 MV radiation isocenter using an Elekta isocenter search algorithm, based on portal images. The 3D radiation isocenter shifts of other photon energy modes relative to the 6 MV were determined. Beam profile scanning for different field sizes was used as an independent method to determine the 2D multiradiation isocenters alignment. To quantify the impact of radiation isocenter offset on targeting accuracy, the 10 MV radiation isocenter was manually offset from that for 6 MV by adjusting the bending magnet current. Because our table isocenter was mechanically aligned to the 6 MV radiation isocenter, the deviation of the table isocentric rotation from the "shifted" 10 MV radiation isocenter after bending magnet adjustment was assessed. Winston‐Lutz test was also performed to confirm the overall radiation isocenter positioning accuracy for all photon energies. The portal image method showed the radiation isocenter of the 10 MV flattening filter‐free mode deviated from others before beam parameter adjustment. After the adjustment, the deviation was greatly improved from 0.96 to 0.35 mm relative to the 6 MV radiation isocenter. The same finding was confirmed by the profile‐scanning method. The maximum deviation of the table isocentric rotation from the 10 MV radiation isocenter was observed to linearly increase with the offset between 6 and 10 MV radiation isocenter; 1 mm radiation isocenter offset can translate to almost 2 mm maximum deviation of the table isocentric rotation from the 10 MV radiation isocenter. The alignment of the multiradiation isocenters is particularly important for high‐precision radiotherapy. Our study provides the medical physics community with a quantitative measure of the multiradiation isocenters alignment. A routine QA method should be considered, to examine the radiation isocenters alignment during the linac acceptance. PACS number: 87.55.Qr, 87.56.bd, 87.56.Fc

Constancy checks of a well‐type ionization chamber should be performed regularly as part of a quality assurance regime. The goal of this work was to test the feasibility of using a linear accelerator and an orthovoltage unit to check the constancy of a well‐type chamber's response to an external radiation source. The reproducibility, linearity with dose, variation with dose‐rate, and variation between energy‐matched units of the well‐type chamber response when exposed to 6 MV beams was examined. The robustness to errors in establishing the measurement conditions, including setting the source‐to‐surface distance and gantry angle, rotation of the chamber around the central axis of the beam, and the effect of changing the length of the chamber cable exposed to the field, were tested. The reproducibility and linearity with dose of the chamber response, and robustness to errors in establishing the measurement conditions for 100 kVp and 250 kVp beams from an orthovoltage unit, were also examined. The combined uncertainty, including contributions from errors in establishing the reference conditions, for well‐type chamber measurements using a 6 MV beam from a linear accelerator is 1.0%. The combined uncertainties for measurements using 100 and 250 kVp beams were 1.8% and 1.5%, respectively. When focus‐source distance errors were reduced to ≤1mm, the combined uncertainties for the 100 and 250 kVp beams were 1.2% and 1.1%, respectively, when the dose to the chamber was confined to the linear region of the dose‐response curve. The response of a well‐type chamber should remain constant to within 1.2% when exposed to a constant dose from an external beam unit, if reference conditions can be reproducibly established. However, the uncertainty for establishing reference conditions for output measurements for an orthovoltage unit can be reduced, which would justify a reduction of the tolerance for constancy measurements. PACS numbers: 87.55.Qr, 87.56.Fc

Internal lead shielding is utilized during superficial electron beam treatments of the head and neck, such as lip carcinoma. Methods for predicting backscattered dose include the use of empirical equations or performing physical measurements. The accuracy of these empirical equations required verification for the local electron beams. In this study, a Monte Carlo model of a Siemens Artiste linac was developed for 6, 9, 12, and 15 MeV electron beams using the EGSnrc MC package. The model was verified against physical measurements to an accuracy of better than 2% and 2 mm. Multiple MC simulations of lead interfaces at different depths, corresponding to mean electron energies in the range of 0.2–14 MeV at the interfaces, were performed to calculate electron backscatter values. The simulated electron backscatter was compared with current empirical equations to ascertain their accuracy. The major finding was that the current set of backscatter equations does not accurately predict electron backscatter, particularly in the lower energies region. A new equation was derived which enables estimation of electron backscatter factor at any depth upstream from the interface for the local treatment machines. The derived equation agreed to within 1.5% of the MC simulated electron backscatter at the lead interface and upstream positions. Verification of the equation was performed by comparing to measurements of the electron backscatter factor using Gafchromic EBT2 film. These results show a mean value of 0.997±0.022 to 1σ of the predicted values of electron backscatter. The new empirical equation presented can accurately estimate electron backscatter factor from lead shielding in the range of 0.2 to 14 MeV for the local linacs. PACS numbers: 87.53.Bn, 87.55.K‐, 87.56.bd

Background: Ovarian Cancer is a broad spectrum of diseases comprising several subtypes. Three major categories in younger women are germ cell tumor, sex cord stromal tumor and epithelial ovarian neoplasia. Objective: literature search was for an update on management of ovarian cancer in young women. Context: Germ cell tumor is suspected in young girls presenting with solid ovarian neoplasm as abdominal mass, discomfort, dyspnea or pain abdomen. Preoperative evaluation should include thorough clinical examination with biochemical profile tumor markers and imaging techniques. When prepubertal girls present with precocious puberty, clitoromegaly, development of secondary sexual character, one should suspect juvenile granulosa theca cell tumor. Often serum beta inhibin is elevated in these cases. Young women are not immune to other tumors. Surgery should be fertility sparing, salphingo -oopherectomy, omentectomy, peritoneal cytology, retro peritoneal lymphadenectomy whenever indicated. Except Stage I A puredysgerminoma, Stage IA grade 1 immature teratoma, Stage IA /B grade 1 epithelial ovarian carcinoma, all other histopathological types irrespective of the stage of the disease require adjuvant chemotherapy. Conclusion: Girls, young women can have ovarian cancer conservative therapy. However treatment needs to be individualized. Except stage IA disease all other patient require adjuvant chemotherapy apart from fertility sparing surgery.

This study aims at selecting and evaluating a ripple filter design compatible with non-isocentric proton and carbon ion scanning beam treatment delivery for a compact nozzle. The use of non-isocentric treatments when the patient is shifted as close as possible towards the nozzle exit allows for a reduction in the air gap and thus an improvement in the quality of scanning proton beam treatment delivery. Reducing the air gap is less important for scanning carbon ions, but ripple filters are still necessary for scanning carbon ion beams to reduce the number of energy steps required to deliver homogeneous SOBP. The proper selection of ripple filters also allows a reduction in the possible transverse and depth-dose inhomogeneities that could appear in non-isocentric conditions in particular. A thorough review of existing ripple filter designs over the past 16 years is performed and a design for non-isocentric treatment delivery is presented. A unique ripple filter quality index (QIRiFi) independent of the particle type and energy and representative of the ratio between energy modulation and induced scattering is proposed. The Bragg peak width evaluated at the 80% dose level (BPW80) is proposed to relate the energy modulation of the delivered Bragg peaks and the energy layer step size allowing the production of homogeneous SOBP. Gate/Geant4 Monte Carlo simulations have been validated for carbon ion and ripple filter simulations based on measurements performed at CNAO and subsequently used for a detailed analysis of the proposed ripple filter design. A combination of two ripple filters in a series has been validated for non-isocentric delivery and did not show significant transverse and depth-dose inhomogeneities. Non-isocentric conditions allow a significant reduction in the spot size at the patient entrance (up to 350% and 200% for protons and carbon ions with range shifter, respectively), and therefore in the lateral penumbra in the patients.

Microbeam radiation therapy (MRT), a novel form of spatially fractionated radiotherapy (RT), uses arrays of synchrotron-generated X-ray microbeams (MB). MRT has been identified as a promising treatment concept that might be applied to patients with malignant central nervous system (CNS) tumours for whom, at the current stage of development, no satisfactory therapy is available yet. Preclinical experimental studies have shown that the CNS of healthy rodents and piglets can tolerate much higher radiation doses delivered by spatially separated MBs than those delivered by a single, uninterrupted, macroscopically wide beam. High-dose, high-precision radiotherapies such as MRT with reduced probabilities of normal tissue complications offer prospects of improved therapeutic ratios, as extensively demonstrated by results of experiments published by many international groups in the last two decades. The significance of developing MRT as a new RT approach cannot be understated. Up to 50% of cancer patients receive conventional RT, and any new treatment that provides better tumour control whilst preserving healthy tissue is likely to significantly improve patient outcomes.

The principle of the compact Compton source is presented briefly. In collision with an ultrarelativistic electron bunch a laser pulse is back-scattered as hard X-rays. The radiation cone has an opening of a few mrad, and the energy bandwidth is a few percent. The electrons that have an energy of the order of a few tens of MeV either circulate in storage ring, or are injected to a linac at a frequency of 10-100 MHz. At the interaction point the electron bunch collides with the laser pulse that has been amplified in a Fabry-Perot resonator. There are several machines in design or construction phase, and projected fluxes are 1012 to 10(14) photons/s. The flux available at 80 keV from the ThomX machine is compared with that used in the Stereotactic Synchrotron Radiation Therapy clinical trials. It is concluded that ThomX has the potential of serving as the radiation source in future radiation therapy programs, and that ThomX can be integrated in hospital environment. (C) 2015 Published by Elsevier Ltd on behalf of Associazione Italiana di Fisica Medica.

For the determination of absorbed dose to water D ,using thermolumeniscence (TL) probes in a beam different from that used for calibration, correction factors for radiation type and radiation quality k E and k Q are needed. Values for k E and k Q for two different shapes of LiF probes (rods and disks) were obtained for high-energy photon and electron beams. The relation between the absorbed dose to the medium (water) D , measured by ion-chambers according to DIN 6800-2, 2008 and TL-probes having a 60 Co-calibration factor, leads for each shape and each batch of LiF probes to correction factors for radiation type and radiation quality k E and k Q. . The influence of the shape on the correction factor of the probes amounts in our experiment up to 2%. Therefore, it is recommended that the correction factors k E and k Q for rods and disks should be checked for each batch of LiF-detectors.

Radiographic film dosimetry suffers from its energy dependence in proton dosimetry. This study sought to develop a method of measuring proton beams by the film and to evaluate film response to proton beams for the constancy check of depth dose (DD). It also evaluated the film for profile measurements. To achieve this goal, from DDs measured by film and ion chamber (IC), calibration factors (ratios of dose measured by IC to film responses) as a function of depth in a phantom were obtained. These factors imply variable slopes (with proton energy and depth) of linear characteristic curves that relate film response to dose. We derived a calibration method that enables utilization of the factors for acquisition of dose from film density measured at later dates by adapting to a potentially altered processor condition. To test this model, the characteristic curve was obtained by using EDR2 film and in‐phantom film dosimetry in parallel with a 149.65 MeV proton beam, using the method. An additional validation of the model was performed by concurrent film and IC measurement perpendicular to the beam at various depths. Beam profile measurements by the film were also evaluated at the center of beam modulation. In order to interpret and ascertain the film dosimetry, Monte Carlos simulation of the beam was performed, calculating the proton fluence spectrum along depths and off‐axis distances. By multiplying respective stopping powers to the spectrum, doses to film and water were calculated. The ratio of film dose to water dose was evaluated. Results are as follows. The characteristic curve proved the assumed linearity. The measured DD approached that of IC, but near the end of the spread‐out Bragg peak (SOBP), a spurious peak was observed due to the mismatch of distal edge between the calibration and measurement films. The width of SOBP and the proximal edge were both reproducible within a maximum of 5 mm; the distal edge was reproducible within 1 mm. At 5 cm depth, the dose was reproducible within 10%. These large discrepancies were identified to have been contributed by film processor uncertainty across a layer of film and the misalignment of film edge to the frontal phantom surface. The deviations could drop from 5 to 2 mm in SOBP and from 10% to 4.5% at 5 cm depth in a well‐controlled processor condition (i.e., warm up). In addition to the validation of the calibration method done by the DD measurements, the concurrent film and IC measurement independently validated the model by showing the constancy of depth‐dependent calibration factors. For profile measurement, the film showed good agreement with ion chamber measurement. In agreement with the experimental findings, computationally obtained ratio of film dose to water dose assisted understanding of the trend of the film response by revealing relatively large and small variances of the response for DD and beam profile measurements, respectively. Conclusions are as follows. For proton beams, radiographic film proved to offer accurate beam profile measurements. The adaptive calibration method proposed in this study was validated. Using the method, film dosimetry could offer reasonably accurate DD constancy checks, when provided with a well‐controlled processor condition. Although the processor warming up can promote a uniform processing across a single layer of the film, the processing remains as a challenge. PACS number: 87

The need to accurately and efficiently verify both output and dose profiles creates significant challenges in quality assurance of pencil beam scanning (PBS) proton delivery. A system for PBS QA has been developed that combines a new two-dimensional ionization chamber array in a waterproof housing that is scanned in a water phantom. The MatriXX PT has the same detector array arrangement as the standard math formula but utilizes a smaller 2 mm plate spacing instead of 5 mm. Because the bias voltage of the MatriXX PT and Evolution cannot be changed, PPC40 and FC65-G ionization chambers were used to assess recombination effects. The PPC40 is a parallel plate chamber with an electrode spacing of 2 mm, while the FC65-G is a Farmer chamber FC65-G with an electrode spacing of 2.8 mm. Three bias voltages (500, 200, and 100 V) were used for both detectors to determine which radiation type (continuous, pulse or pulse-scanned beam) could closely estimate math formula from the ratios of charges collected. In comparison with the math formula, a significant improvement in measurement of absolute dose with the MatriXX PT was observed. While dose uncertainty of the math formula can be up to 4%, it is math formula for the MatriXX PT. Therefore the math formula should not be used for QA of PBS for conditions in which ion recombination is not negligible. Farmer chambers should be used with caution for measuring the absolute dose of PBS beams, as the uncertainty of math formula can be math formula; chambers with an electrode spacing of 2 mm or smaller are recommended. PACS number: 87.53.Qc OA gold