Stereoscopic X-ray image and thermo-optical surface guidance for breast cancer radiotherapy in deep inspiration breath-hold.

PURPOSE: To investigate the feasibility of a thermo-optical surface imaging (SGRT) system combined with room-based stereoscopic X­ray image guidance (IGRT) in a dedicated breast deep inspiration breath-hold (DIBH) irradiation workflow. In this context, benchmarking of portal imaging (EPID) and cone-beam CT (CBCT) against stereoscopic X­rays was performed. METHODS: SGRT + IGRT data of 30 left-sided DIBH breast patients (1 patient with bilateral cancer) treated in 351 fractions using thermo-optical surface imaging and X-ray IGRT were retrospectively analysed. Patients were prepositioned based on a free-breathing surface reference derived from a CT scan. Once the DIBH was reached using visual feedback, two stereoscopic X­ray images were acquired and registered to the digitally reconstructed radiographs derived from the DIBH CT. Based on this registration, a couch correction was performed. Positioning and monitoring by surface and X-ray imaging were verified by protocol-based EPID or CBCT imaging at selected fractions and the calculation of residual geometric deviations. RESULTS: The median X­ray-derived couch correction vector was 4.9 (interquartile range [IQR] 3.3-7.1) mm long. Verification imaging was performed for 134 fractions (216 RT field verifications) with EPID and for 37 fractions with CBCT, respectively. The median 2D/3D deviation vector length over all verification images was 2.5 (IQR 1.6-3.9) mm/3.4 (IQR 2.2-4.8) mm for EPID/CBCT, both being well within the planning target volume (PTV) margins (7 mm). A moderate correlation (0.49-0.65) was observed between the surface signal and X-ray position in DIBH. CONCLUSION: DIBH treatments using thermo-optical SGRT and X-ray IGRT were feasible for breast cancer patients. Stereoscopic X­ray positioning was successfully verified by standard IGRT techniques.

The role of artificial intelligence in informed patient consent for radiotherapy treatments-a case report.

Recent advancements in large language models (LMM; e.g., ChatGPT (OpenAI, San Francisco, California, USA)) have seen widespread use in various fields, including healthcare. This case study reports on the first use of LMM in a pretreatment discussion and in obtaining informed consent for a radiation oncology treatment. Further, the reproducibility of the replies by ChatGPT 3.5 was analyzed. A breast cancer patient, following legal consultation, engaged in a conversation with ChatGPT 3.5 regarding her radiotherapy treatment. The patient posed questions about side effects, prevention, activities, medications, and late effects. While some answers contained inaccuracies, responses closely resembled doctors' replies. In a final evaluation discussion, the patient, however, stated that she preferred the presence of a physician and expressed concerns about the source of the provided information. The reproducibility was tested in ten iterations. Future guidelines for using such models in radiation oncology should be driven by medical professionals. While artificial intelligence (AI) supports essential tasks, human interaction remains crucial.

DNA-PKcs Inhibition Sensitizes Human Chondrosarcoma Cells to Carbon Ion Irradiation via Cell Cycle Arrest and Telomere Capping Disruption.

In order to overcome the resistance to radiotherapy in human chondrosarcoma cells, the prevention from efficient DNA repair with a combined treatment with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) inhibitor AZD7648 was explored for carbon ion (C-ion) as well as reference photon (X-ray) irradiation (IR) using gene expression analysis, flow cytometry, protein phosphorylation, and telomere length shortening. Proliferation markers and cell cycle distribution changed significantly after combined treatment, revealing a prominent G2/M arrest. The expression of the G2/M checkpoint genes cyclin B, CDK1, and WEE1 was significantly reduced by IR alone and the combined treatment. While IR alone showed no effects, additional AZD7648 treatment resulted in a dose-dependent reduction in AKT phosphorylation and an increase in Chk2 phosphorylation. Twenty-four hours after IR, the key genes of DNA repair mechanisms were reduced by the combined treatment, which led to impaired DNA repair and increased radiosensitivity. A time-dependent shortening of telomere length was observed in both cell lines after combined treatment with AZD7648 and 8 Gy X-ray/C-ion IR. Our data suggest that the inhibition of DNA-PKcs may increase sensitivity to X-rays and C-ion IR by impairing its functional role in DNA repair mechanisms and telomere end protection.

The ATR Inhibitor VE-821 Enhances the Radiosensitivity and Suppresses DNA Repair Mechanisms of Human Chondrosarcoma Cells.

To overcome the resistance to radiotherapy in chondrosarcomas, the prevention of efficient DNA repair with an additional treatment was explored for particle beams as well as reference X-ray irradiation. The combined treatment with DNA repair inhibitors-with a focus on ATRi VE-821-and proton or carbon ions irradiation was investigated regarding cell viability, proliferation, cell cycle distribution, MAPK phosphorylation, and the expression of key DNA repair genes in two human chondrosarcoma cell lines. Pre-treatment with the PARPis Olaparib or Veliparib, the ATMi Ku-55933, and the ATRi VE-821 resulted in a dose-dependent reduction in viability, whereas VE-821 has the most efficient response. Quantification of γH2AX phosphorylation and protein expression of the DNA repair pathways showed a reduced regenerative capacity after irradiation. Furthermore, combined treatment with VE-821 and particle irradiation increased MAPK phosphorylation and the expression of apoptosis markers. At the gene expression and at the protein expression/phosphorylation level, we were able to demonstrate the preservation of DNA damage after combined treatment. The present data showed that the combined treatment with ATMi VE-821 increases the radiosensitivity of human chondrosarcoma cells in vitro and significantly suppresses efficient DNA repair mechanisms, thus improving the efficiency of radiotherapy.

Radiobiological Assessment of Targeted Radionuclide Therapy with [177Lu]Lu-PSMA-I&T in 2D vs. 3D Cell Culture Models.

In vitro therapeutic efficacy studies are commonly conducted in cell monolayers. However, three-dimensional (3D) tumor spheroids are known to better represent in vivo tumors. This study used [177Lu]Lu-PSMA-I&T, an already clinically applied radiopharmaceutical for targeted radionuclide therapy against metastatic castrate-resistant prostate cancer, to demonstrate the differences in the radiobiological response between 2D and 3D cell culture models of the prostate cancer cell lines PC-3 (PSMA negative) and LNCaP (PSMA positive). After assessing the target expression in both models via Western Blot, cell viability, reproductive ability, and growth inhibition were assessed. To investigate the geometric effects on dosimetry for the 2D vs. 3D models, Monte Carlo simulations were performed. Our results showed that PSMA expression in LNCaP spheroids was highly preserved, and target specificity was shown in both models. In monolayers of LNCaP, no short-term (48 h after treatment), but only long-term (14 days after treatment) radiobiological effects were evident, showing decreased viability and reproductive ability with the increasing activity. Further, LNCaP spheroid growth was inhibited with the increasing activity. Overall, treatment efficacy was higher in LNCaP spheroids compared to monolayers, which can be explained by the difference in the resulting dose, among others.

Cellular and Molecular Biological Alterations after Photon, Proton, and Carbon Ions Irradiation in Human Chondrosarcoma Cells Linked with High-Quality Physics Data.

Chondrosarcomas are particularly difficult to treat due to their resistance to chemotherapy and radiotherapy. However, particle therapy can enhance local control and patient survival rates. To improve our understanding of the basic cellular radiation response, as a function of dose and linear energy transfer (LET), we developed a novel water phantom-based setup for cell culture experiments and characterized it dosimetrically. In a direct comparison, human chondrosarcoma cell lines were analyzed with regard to their viability, cell proliferation, cell cycle, and DNA repair behavior after irradiation with X-ray, proton, and carbon ions. Our results clearly showed that cell viability and proliferation were inhibited according to the increasing ionization density, i.e., LET, of the irradiation modes. Furthermore, a prominent G2/M arrest was shown. Gene expression profiling proved the upregulation of the senescence genes CDKN1A (p21), CDKN2A (p16NK4a), BMI1, and FOXO4 after particle irradiation. Both proton or C-ion irradiation caused a positive regulation of the repair genes ATM, NBN, ATXR, and XPC, and a highly significant increase in XRCC1/2/3, ERCC1, XPC, and PCNA expression, with C-ions appearing to activate DNA repair mechanisms more effectively. The link between the physical data and the cellular responses is an important contribution to the improvement of the treatment system.

Early morbidity and dose-volume effects in definitive radiochemotherapy for locally advanced cervical cancer: a prospective cohort study covering modern treatment techniques.

PURPOSE: Predicting morbidity for patients with locally advanced cervix cancer after external beam radiotherapy (EBRT) based on dose-volume parameters remains an unresolved issue in definitive radiochemotherapy. The aim of this prospective study was to correlate patient characteristics and dose-volume parameters to various early morbidity endpoints for different EBRT techniques, including volumetric modulated arc therapy (VMAT) and adaptive radiotherapy (ART). METHODS AND MATERIALS: The study population consisted of 48 patients diagnosed with locally advanced cervix cancer, treated with definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT). Multiple questionnaires (CTCAE 4.03, QLQ-C30 and EORTC QLQ-CX24) were assessed prospectively for patients treated with different EBRT techniques, including online adaptive VMAT. Contouring and treatment planning was based on the EMBRACE protocols. Acute toxicity, classified as general, gastrointestinal (GI) or genitourinary (GU) and their corresponding dose-volume histograms (DVHs) were first correlated by applying least absolute shrinkage and selection operator (LASSO) and subsequently evaluated by multiple logistic binomial regression. RESULTS: The treated EBRT volumes varied for the different techniques with ~2500 cm3 for 3D conformal radiotherapy (3D-CRT), ~2000 cm3 for EMBRACE­I VMAT, and ~1800 cm3 for EMBRACE-II VMAT and ART. In general, a worsening of symptoms during the first 5 treatment weeks and recovery afterwards was observed. Dose-volume parameters significantly correlating with stool urgency, rectal and urinary incontinence were as follows: bowel V40Gy < 250 cm3, rectum V40Gy < 80% and bladder V40Gy < 80-90%. CONCLUSION: This prospective study demonstrated the impact of EBRT treatment techniques in combination with chemotherapy on early morbidity. Dose-volume effects for dysuria, urinary incontinence, stool urgency, diarrhea, rectal bleeding, rectal incontinence and weight loss were found.

Hypofractionated stereotactic photon radiotherapy of choroidal melanoma: 20-year experience.

BACKGROUND: To evaluate the long-term results after hypofractionated stereotactic photon radiotherapy (SRT) in patients with choroidal melanoma treated between 1997 and 2016. MATERIAL AND METHODS: A total of 335 patients (183 male and 152 female) with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated with linear accelerator-based SRT at the Medical University of Vienna. All patients received five fractions with either 10, 12 or 14 Gy per fraction. A complete ophthalmic examination including visual acuity and measurement of the tumor base and height using standardized A- and B-scan ultrasonography was performed every 3 months in the first 2 years, every 6 months until 5 years and yearly thereafter. Early and late adverse side effects were assessed at every follow-up visit. RESULTS: The median overall follow-up was 78.6 months (39.1 to 113.7 months). Local tumor control was 95.4% after 10 and 12 years, respectively. Fifty-four patients developed metastatic disease, and 31 died during the follow-up. Mean visual acuity decreased from 0.55 Snellen at baseline to 0.05 Snellen at the last individual follow-up. Ischemic retinopathy (192/335cases) and optic neuropathy (174/335cases) were the most common radiogenic side effects, followed by radiogenic cataract (n = 127), neovascular glaucoma (n = 71) and corneal epithelium defects (n = 49). Enucleation was performed in 54 patients mostly due to neovascular glaucoma (n = 41) or tumor recurrence (n = 10) during the study period. The eye retention rate was 79.7% after 10 and 12 years. CONCLUSION: Hypofractionated stereotactic photon radiotherapy showed a high rate of local tumor control for choroidal melanoma and an acceptable rate of radiogenic side effects.

The influence of errors in small field dosimetry on the dosimetric accuracy of treatment plans.

Background: Dosimetric effects of inaccuracies of output factors (OFs) implemented in treatment planning systems (TPSs) were investigated.Materials and methods: Modified beam models (MBM) for which the OFs of small fields (down to 1 × 1 cm2) were increased by up to 12% compared to the original beam models (OBM) were created for two TPSs. These beam models were used to recalculate treatment plans of different complexity. Treatment plans using stereotactic 3D-conformal (s3D-CRT) for brain metastasis as well as VMAT plans for head and neck and prostate cancer patients were generated. Dose distributions calculated with the MBM and the OBM were compared to measured dose distributions acquired using film dosimetry and a 2D-detector-array. For the s3D-CRT plans the calculated and measured dose at the isocenter was evaluated. For VMAT, gamma pass rates (GPRs) were calculated using global gamma index with 3%/3 mm, 2%/3 mm, 1%/3 mm and 2%/2 mm with a 20% threshold. Contribution of small fields to the total fluence was expressed as the ratio (F) of fluence trough leaf openings smaller than 2 cm to the total fluence.Results: Using film dosimetry for the s3D-CRT plans, the average of the ratio of calculated dose to measured dose at the isocenter was 1.01 and 1.06 for the OBM and MBM model, respectively. A significantly lower GPR of the MBM compared to the OBM was only found for the localized prostate cases (F = 12.4%) measured with the 2D-detector-array and an acceptance criterion of 1%/3 mm.Conclusion: The effects of uncertainties in small field OFs implemented in TPSs are most pronounced for s3D-CRT cases and can be clearly identified using patient specific quality assurance. For VMAT these effects mainly remain undetected using standard patient specific quality assurance. Using tighter acceptance criteria combined with an analysis of the fluence generated by small fields can help identifying inaccuracies of OFs implemented in TPSs.

Testing the methodology for a dosimetric end-to-end audit of IMRT/VMAT: results of IAEA multicentre and national studies.

Introduction: Within an International Atomic Energy Agency (IAEA) co-ordinated research project (CRP), a remote end-to-end dosimetric quality audit for intensity modulated radiation therapy (IMRT)/ volumetric arc therapy (VMAT) was developed to verify the radiotherapy chain including imaging, treatment planning and dose delivery. The methodology as well as the results obtained in a multicentre pilot study and national trial runs conducted in close cooperation with dosimetry audit networks (DANs) of IAEA Member States are presented.Material and methods: A solid polystyrene phantom containing a dosimetry insert with an irregular solid water planning target volume (PTV) and organ at risk (OAR) was designed for this audit. The insert can be preloaded with radiochromic film and four thermoluminescent dosimeters (TLDs). For the audit, radiotherapy centres were asked to scan the phantom, contour the structures, create an IMRT/VMAT treatment plan and irradiate the phantom. The dose prescription was to deliver 4 Gy to the PTV in two fractions and to limit the OAR dose to a maximum of 2.8 Gy. The TLD measured doses and film measured dose distributions were compared with the TPS calculations.Results: Sixteen hospitals from 13 countries and 64 hospitals from 6 countries participated in the multicenter pilot study and in the national runs, respectively. The TLD results for the PTV were all within ±5% acceptance limit for the multicentre pilot study, whereas for national runs, 17 participants failed to meet this criterion. All measured doses in the OAR were below the treatment planning constraint. The film analysis identified seven plans in national runs below the 90% passing rate gamma criteria.Conclusion: The results proved that the methodology of the IMRT/VMAT dosimetric end-to-end audit was feasible for its intended purpose, i.e., the phantom design and materials were suitable; the phantom was easy to use and it was robust enough for shipment. Most importantly the audit methodology was capable of identifying suboptimal IMRT/VMAT delivery.

Phantom design and dosimetric characterization for multiple simultaneous cell irradiations with active pencil beam scanning.

A new phantom was designed for in vitro studies on cell lines in horizontal particle beams. The phantom enables simultaneous irradiation at multiple positions along the beam path. The main purpose of this study was the detailed dosimetric characterization of the phantom which consists of various heterogeneous structures. The dosimetric measurements described here were performed under non-reference conditions. The experiment involved a CT scan of the phantom, dose calculations performed with the treatment planning system (TPS) RayStation employing both the Pencil Beam (PB) and Monte Carlo (MC) algorithms, and proton beam delivery. Two treatment plans reflecting the typical target location for head and neck cancer and prostate cancer treatment were created. Absorbed dose to water and dose homogeneity were experimentally assessed within the phantom along the Bragg curve with ionization chambers (ICs) and EBT3 films. LETd distributions were obtained from the TPS. Measured depth dose distributions were in good agreement with the Monte Carlo-based TPS data. Absorbed dose calculated with the PB algorithm was 4% higher than the absorbed dose measured with ICs at the deepest measurement point along the spread-out Bragg peak. Results of experiments using melanoma (SKMel) cell line are also presented. The study suggested a pronounced correlation between the relative biological effectiveness (RBE) and LETd, where higher LETd leads to elevated cell death and cell inactivation. Obtained RBE values ranged from 1.4 to 1.8 at the survival level of 10% (RBE10). It is concluded that dosimetric characterization of a phantom before its use for RBE experiments is essential, since a high dosimetric accuracy contributes to reliable RBE data and allows for a clearer differentiation between physical and biological uncertainties.

Automated volumetric modulated arc therapy planning for whole pelvic prostate radiotherapy.

BACKGROUND: For several tumor entities, automated treatment planning has improved plan quality and planning efficiency, and may enable adaptive treatment approaches. Whole-pelvic prostate radiotherapy (WPRT) involves large concave target volumes, which present a challenge for volumetric arc therapy (VMAT) optimization. This study evaluates automated VMAT planning for WPRT-VMAT and compares the results with manual expert planning. METHODS: A system for fully automated multi-criterial plan generation was configured for each step of sequential-boost WPRT-VMAT, with final "autoVMAT" plans being automatically calculated by the Monaco treatment planning system (TPS; Elekta AB, Stockholm, Sweden). Configuration was based on manually generated VMAT plans (manualVMAT) of 5 test patients, the planning protocol, and discussions with the treating physician on wishes for plan improvements. AutoVMAT plans were then generated for another 30 evaluation patients and compared to manualVMAT plans. For all 35 patients, manualVMAT plans were optimized by expert planners using the Monaco TPS. RESULTS: AutoVMAT plans exhibited strongly improved organ sparing and higher conformity compared to manualVMAT. On average, mean doses (Dmean) of bladder and rectum were reduced by 10.7 and 4.5 Gy, respectively, by autoVMAT. Prostate target coverage (V95%) was slightly higher (+0.6%) with manualVMAT. In a blinded scoring session, the radiation oncologist preferred autoVMAT plans to manualVMAT plans for 27/30 patients. All treatment plans were considered clinically acceptable. The workload per patient was reduced by > 70 min. CONCLUSION: Automated VMAT planning for complex WPRT dose distributions is feasible and creates treatment plans that are generally dosimetrically superior to manually optimized plans.

Multiparametric MRI of the prostate at 3 T: limited value of 3D (1)H-MR spectroscopy as a fourth parameter.

PURPOSE: The aim of our study was to assess whether multiparametric magnetic resonance imaging (MP-MRI) of the prostate with three parameters (PS3: T2-weighted, DWI, and DCE) benefits from an additional fourth parameter (PS4: including (1)H-MRSI) in the detection and grading of prostate cancer (PCa) at 3 T. METHODS: MP-MRI was performed in 64 patients (mean 66.7 years, mean PSA 13 ng/ml). Reference standard was obtained by histopathology. Two readers independently evaluated the images. A summation score of each individual parameter for three parameters (PS3) and for four parameters (PS4) was calculated. RESULTS: In 52 (81.3 %) of 64 patients, histopathology confirmed a PCa. The diagnostic performance for PCa detection of PS4 (O1: 91.7 %, O2: 91.3 %) equaled that of PS3 (O1: 92.8 %, O2: 92.2 %, P > 0.05). Prediction of high-grade PCa by PS4 (O1: 75.1 %, O2: 74.7 %) was as good as with PS3 (O1: 75.1 %, O2: 72.8 %, P > 0.05). Kappa agreement between the two readers was substantial (0.734 PS4) to moderate (0.558 PS3). CONCLUSIONS: MP-MRI with four parameters including (1)H-MRSI does not increase the detection and grading of prostate cancer at 3 T compared to MP-MRI with three parameters. A sum score accurately detects PCa at 3 T without an endorectal coil and shows potential for the prediction of tumor grade.

Can particle beam therapy be improved using helium ions? - a planning study focusing on pediatric patients.

Aim To explore the potential of scanned helium ion beam therapy ((4)He) compared to proton therapy in a comparative planning study focusing on pediatric patients. This was motivated by the superior biological and physical characteristics of (4)He. Material and methods For eleven neuroblastoma (NB), nine Hodgkin lymphoma (HL), five Wilms tumor (WT), five ependymoma (EP) and four Ewing sarcoma (EW) patients, treatment plans were created for protons and (4)He. Dose prescription to the planning target volume (PTV) was 21 Gy [relative biological effectiveness (RBE)] (NB), 19.8 Gy (RBE) (HL), 25.2 Gy (RBE) for the WT boost volume and 54 Gy (RBE) for EP and EW patients. A pencil beam algorithm for protons (constant RBE = 1.1) and (4)He was implemented in the treatment planning system Hyperion. For (4)He the relative biological effectiveness (RBE) was calculated with a 'zonal' model based on different linear energy transfer regions. Results Target constraints were fulfilled for all indications. For NB patients differences for kidneys and liver were observed for all dose-volume areas, except the high-dose volume. The body volume receiving up to 12.6 Gy (RBE) was reduced by up to 10% with (4)He. For WT patients the mean and high-dose volume for the liver was improved when using (4)He. For EP normal tissue dose was reduced using (4)He with 12.7% of the voxels receiving higher doses using protons. For HL and EW sarcoma patients the combination of large PTV volumes with the position of the organs at risk (OARs) obliterated the differences between the two particle species, while patients with the heart close to the PTV could benefit from (4)He. Conclusion Treatment plan quality improved with (4)He compared to proton plans, but advantages in OAR sparing were depending on indication and tumor geometries. These first results of scanned (4)He therapy motivate comprehensive research on (4)He, including acquisition of experimental data to improve modeling of (4)He.

Testing the methodology for dosimetry audit of heterogeneity corrections and small MLC-shaped fields: Results of IAEA multi-center studies.

UNLABELLED: The International Atomic Energy Agency (IAEA) has a long tradition of supporting development of methodologies for national networks providing quality audits in radiotherapy. A series of co-ordinated research projects (CRPs) has been conducted by the IAEA since 1995 assisting national external audit groups developing national audit programs. The CRP 'Development of Quality Audits for Radiotherapy Dosimetry for Complex Treatment Techniques' was conducted in 2009-2012 as an extension of previously developed audit programs. MATERIAL AND METHODS: The CRP work described in this paper focused on developing and testing two steps of dosimetry audit: verification of heterogeneity corrections, and treatment planning system (TPS) modeling of small MLC fields, which are important for the initial stages of complex radiation treatments, such as IMRT. The project involved development of a new solid slab phantom with heterogeneities containing special measurement inserts for thermoluminescent dosimeters (TLD) and radiochromic films. The phantom and the audit methodology has been developed at the IAEA and tested in multi-center studies involving the CRP participants. RESULTS: The results of multi-center testing of methodology for two steps of dosimetry audit show that the design of audit procedures is adequate and the methodology is feasible for meeting the audit objectives. A total of 97% TLD results in heterogeneity situations obtained in the study were within 3% and all results within 5% agreement with the TPS predicted doses. In contrast, only 64% small beam profiles were within 3 mm agreement between the TPS calculated and film measured doses. Film dosimetry results have highlighted some limitations in TPS modeling of small beam profiles in the direction of MLC leave movements. DISCUSSION: Through multi-center testing, any challenges or difficulties in the proposed audit methodology were identified, and the methodology improved. Using the experience of these studies, the participants could incorporate the auditing procedures in their national programs.

ART for head and neck patients: On the difference between VMAT and IMPT.

UNLABELLED: Anatomical changes in the head-and-neck (H&N) region during the course of treatment can cause deteriorated dose distributions. Different replanning strategies were investigated for volumetric modulated arc therapy (VMAT) and intensity-modulated proton therapy (IMPT). MATERIAL AND METHODS: For six H&N patients two repeated computed tomography (CT) and magnetic resonance (MR) (CT1/MR1 at week 2 and CT2/MR2 at week 4) scans were acquired additionally to the initial planning CT/MR. Organs-at-risk (OARs) and three targets (CTV70Gy, CTV63Gy, CTV56Gy) were delineated on MRs and transferred to respective CT data set. Simultaneously integrated boost plans were created using VMAT (two arcs) and IMPT (four beams). To assess the need of replanning the initial VMAT and IMPT plans were recalculated on repeated CTs. Furthermore, VMAT and IMPT plans were replanned on the repeated CTs. A Demon algorithm was used for deformable registration of the repeated CTs with the initial CT and utilized for dose accumulation. Total dose estimations were performed to compare ART versus standard treatment strategies. RESULTS: Dosimetric evaluation of recalculated plans on CT1 and CT2 showed increasing OAR doses for both, VMAT and IMPT. The target coverage of recalculated VMAT plans was considered acceptable in three cases, while for all IMPT plans it dropped. Adaptation of the treatment reduced D2% for brainstem by 6.7 Gy for VMAT and by 8 Gy for IMPT, for particular patients. These D2% reductions were reaching 9 Gy and 14 Gy for the spinal cord. ART improved target dose homogeneity, especially for protons, i.e. D2% decreased by up to 8 Gy while D98% increased by 1.2 Gy. CONCLUSION: ART showed benefits for both modalities. However, as IMPT is more conformal, the magnitude of dosimetric changes was more pronounced compared to VMAT. Large anatomic variations had a severe impact on treatment plan quality for both VMAT and IMPT. ART is justified in those cases irrespective of treatment modalities.

Novel radiotherapy techniques for involved-field and involved-node treatment of mediastinal Hodgkin lymphoma: when should they be considered and which questions remain open?

PURPOSE: Hodgkin lymphoma (HL) is a highly curable disease. Reducing late complications and second malignancies has become increasingly important. Radiotherapy target paradigms are currently changing and radiotherapy techniques are evolving rapidly. DESIGN: This overview reports to what extent target volume reduction in involved-node (IN) and advanced radiotherapy techniques, such as intensity-modulated radiotherapy (IMRT) and proton therapy-compared with involved-field (IF) and 3D radiotherapy (3D-RT)- can reduce high doses to organs at risk (OAR) and examines the issues that still remain open. RESULTS: Although no comparison of all available techniques on identical patient datasets exists, clear patterns emerge. Advanced dose-calculation algorithms (e.g., convolution-superposition/Monte Carlo) should be used in mediastinal HL. INRT consistently reduces treated volumes when compared with IFRT with the exact amount depending on the INRT definition. The number of patients that might significantly benefit from highly conformal techniques such as IMRT over 3D-RT regarding high-dose exposure to organs at risk (OAR) is smaller with INRT. The impact of larger volumes treated with low doses in advanced techniques is unclear. The type of IMRT used (static/rotational) is of minor importance. All advanced photon techniques result in similar potential benefits and disadvantages, therefore only the degree-of-modulation should be chosen based on individual treatment goals. Treatment in deep inspiration breath hold is being evaluated. Protons theoretically provide both excellent high-dose conformality and reduced integral dose. CONCLUSION: Further reduction of treated volumes most effectively reduces OAR dose, most likely without disadvantages if the excellent control rates achieved currently are maintained. For both IFRT and INRT, the benefits of advanced radiotherapy techniques depend on the individual patient/target geometry. Their use should therefore be decided case by case with comparative treatment planning.

Diamond based integrated detection system for dosimetric and microdosimetric characterization of radiotherapy ion beams.

BACKGROUND: Ion beam therapy allows for a substantial sparing of normal tissues and higher biological efficacy. Synthetic single crystal diamond is a very good material to produce high-spatial-resolution and highly radiation hard detectors for both dosimetry and microdosimetry in ion beam therapy. PURPOSE: The aim of this work is the design, fabrication and test of an integrated waterproof detector based on synthetic single crystal diamond able to simultaneously perform dosimetric and microdosimetric characterization of clinical ion beams. METHODS: The active elements of the integrated diamond device, that is, dosimeter and microdosimeter, were both realized in a Schottky diode configuration featured by different area, thickness, and shape by means of photolithography technologies for the selective growth of intrinsic and boron-doped CVD diamond. The cross-section of the sensitive volume of the dosimetric element is 4 mm2 and 1 µm-thick, while the microdosimetric one has an active cross-sectional area of 100 × 100 µm2 and a thickness of about 6.2 µm. The dosimetric and microdosimetric performance of the developed device was assessed at different depths in a water phantom at the MedAustron ion beam therapy facility using a monoenergetic uniformly scanned carbon ion beam of 284.7 MeV/u and proton beam of 148.7 MeV. The particle flux in the region of the microdosimeter was 6·107  cm2 /s for both irradiation fields. At each depth, dose and dose distributions in lineal energy were measured simultaneously and the dose mean lineal energy values were then calculated. Monte Carlo simulations were also carried out by using the GATE-Geant4 code to evaluate the relative dose, dose averaged linear energy transfer (LETd ), and microdosimetric spectra at various depths in water for the radiation fields used, by considering the contribution from the secondary particles generated in the ion interaction processes as well. RESULTS: Dosimetric and microdosimetric quantities were measured by the developed prototype with relatively low noise (∼2 keV/µm). A good agreement between the measured and simulated dose profiles was found, with discrepancies in the peak to plateau ratio of about 3% and 4% for proton and carbon ion beams respectively, showing a negligible LET dependence of the dosimetric element of the device. The microdosimetric spectra were validated with Monte Carlo simulations and a good agreement between the spectra shapes and positions was found. Dose mean lineal energy values were found to be in close agreement with those reported in the literature for clinical ion beams, showing a sharp increase along the Bragg curve, being also consistent with the calculated LETd for all depths within the experimental error of 10%. CONCLUSIONS: The experimental indicate that the proposed device can allow enhanced dosimetry in particle therapy centers, where the absorbed dose measurement is implemented by the microdosimetric characterization of the radiation field, thus providing complementary results. In addition, the proposed device allows for the reduction of the experimental uncertainties associated with detector positioning and could facilitate the partial overcoming of some drawbacks related to the low sensitivity of diamond microdosimeters to low LET radiation.

Proton dosimetry in a magnetic field: Measurement and calculation of magnetic field correction factors for a plane-parallel ionization chamber.

BACKGROUND: The combination of magnetic resonance imaging and proton therapy offers the potential to improve cancer treatment. The magnetic field (MF)-dependent change in the dosage of ionization chambers in magnetic resonance imaging-integrated proton therapy (MRiPT) is considered by the correction factor k B ⃗ , M , Q $k_{\vec{B},M,Q}$ , which needs to be determined experimentally or computed via Monte Carlo (MC) simulations. PURPOSE: In this study, k B ⃗ , M , Q $k_{\vec{B},M,Q}$ was both measured and simulated with high accuracy for a plane-parallel ionization chamber at different clinical relevant proton energies and MF strengths. MATERIAL AND METHODS: The dose-response of the Advanced Markus chamber (TM34045, PTW, Freiburg, Germany) irradiated with homogeneous 10 × $\times$ 10 cm 2 $^2$ quasi mono-energetic fields, using 103.3, 128.4, 153.1, 223.1, and 252.7 MeV proton beams was measured in a water phantom placed in the MF of an electromagnet with MF strengths of 0.32, 0.5, and 1 T. The detector was positioned at a depth of 2 g/cm 2 $^2$ in water, with chamber electrodes parallel to the MF lines and perpendicular to the proton beam incidence direction. The measurements were compared with TOPAS MC simulations utilizing COMSOL-calculated 0.32, 0.5, and 1 T MF maps of the electromagnet. k B ⃗ , M , Q $k_{\vec{B},M,Q}$ was calculated for the measurements for all energies and MF strengths based on the equation: k B ⃗ , M , Q = M Q M Q B ⃗ $k_{\vec{B},M,Q}=\frac{M_\mathrm{Q}}{M_\mathrm{Q}^{\vec{B}}}$ , where M Q B ⃗ $M_\mathrm{Q}^{\vec{B}}$ and M Q $M_\mathrm{Q}$ were the temperature and air-pressure corrected detector readings with and without the MF, respectively. MC-based correction factors were determined as k B ⃗ , M , Q = D det D det B ⃗ $k_{\vec{B},M,Q}=\frac{D_\mathrm{det}}{D_\mathrm{det}^{\vec{B}}}$ , where D det B ⃗ $D_\mathrm{det}^{\vec{B}}$ and D det $D_\mathrm{det}$ were the doses deposited in the air cavity of the ionization chamber model with and without the MF, respectively. Furthermore, MF effects on the chamber dosimetry are studied using MC simulations, examining the impact on the absorbed dose-to-water ( D W $D_{W}$ ) and the shift in depth of the Bragg peak. RESULTS: The detector showed a reduced dose-response for all measured energies and MF strengths, resulting in experimentally determined k B ⃗ , M , Q $k_{\vec{B},M,Q}$ values larger than unity. For all energies and MF strengths examined, k B ⃗ , M , Q $k_{\vec{B},M,Q}$ ranged between 1.0065 and 1.0205. The dependence on the energy and the MF strength was found to be non-linear with a maximum at 1 T and 252.7 MeV. The MC simulated k B ⃗ , M , Q $k_{\vec{B},M,Q}$ values agreed with the experimentally determined correction factors within their standard deviations with a maximum difference of 0.6%. The MC calculated impact on D W $D_{W}$ was smaller 0.2 %. CONCLUSION: For the first time, measurements and simulations were compared for proton dosimetry within MFs using an Advanced Markus chamber. Good agreement of k B ⃗ , M , Q $k_{\vec{B},M,Q}$ was found between experimentally determined and MC calculated values. The performed benchmarking of the MC code allows for calculating k B ⃗ , M , Q $k_{\vec{B},M,Q}$ for various ionization chamber models, MF strengths and proton energies to generate the data needed for a proton dosimetry protocol within MFs and is, therefore, a step towards MRiPT.