Estimation of Mediastinal Toxicities after Radiotherapy for Hodgkin Lymphoma-A Normal Tissue Complication Analysis of the HD16/17 Trial by the German Hodgkin Study Group.

PURPOSE: Hodgkin lymphoma is a hematologic malignancy with excellent outcomes even in advanced stages. Consequently, the importance of treatment-associated toxicity increases. However, the exact estimation of individualized rates is difficult due to different disease extents, treatment strategies and techniques. The following analysis aims at a pre-treatment estimation of relevant mediastinal toxicities. METHODS: Normal tissue complication probability calculations were used to evaluate the toxicity rates for the heart, lungs and female breast of patients undergoing radiotherapy for early-stage Hodgkin lymphoma. Overall, 45 Patients of the HD16 and HD17 trials by the German Hodgkin study group were included and risks were calculated using the Lyman-Kutcher-Burman model. RESULTS: The median values for pericarditis, pneumonitis and fibrosis of the left or right breast were 0.0%, 0.0%, 0.7% and 0.6% in the HD16 cohort, and 0.0%, 0.1%, 1.1% and 1.0% in the HD17 cohort, respectively. Correspondingly, none of the included patients displayed any of the evaluated toxicities during clinical follow-up. The use of higher doses (30 Gy) in the HD17 cohort led to an increase in toxicity compared to the HD16 cohort (20 Gy). No significant influence of the planning target volume size or the radiation technique could be found in this study. CONCLUSION: Both the clinically observed and calculated toxicity rates corroborate the overall low-risk profile of radiotherapy for Hodgkin lymphoma. Further treatment individualization will be attempted in the future.

Impact of Modern Low Dose Involved Site Radiation Therapy on Normal Tissue Toxicity in Cervicothoracic Non-Hodgkin Lymphomas: A Biophysical Study.

This biophysical study aimed to determine fitting parameters for the Lyman-Kutcher-Burman (LKB) dose-response model for normal tissue complication probability (NTCP) calculations of acute side effects and to investigate the impact of reduced radiation doses on the probability of their occurrence in supradiaphragmatic non-Hodgkin lymphoma (NHL) irradiation. A cohort of 114 patients with NHL in the cervicothoracic region, treated between 2015 and 2021 at the University Hospitals of Münster, Hamburg, and Essen, with involved site radiation therapy (ISRT), were included. Among them, 68 patients with aggressive NHL (a-NHL) received consolidative radiation therapy with 24-54 Gy following (R-)CHOP chemotherapy. Additionally, 46 patients with indolent NHL (i-NHL) underwent radiotherapy with 22.5-45.0 Gy. Two treatment plans were prospectively created for each patient (a-NHL: 30.0/40.0 Gy; i-NHL: 24.0/30.0 Gy). NTCP were then calculated using the optimized LKB model. The adapted dose-response models properly predicted the patient's probability of developing acute side effects when receiving doses ≤ 50 Gy. In addition, it was shown that reduced radiation doses can influence the NTCP of acute side effects depending on the aggressiveness of NHL significantly. This study provided a foundation to prospectively assess the probability of adverse side effects among today's reduced radiation doses in the treatment of NHL.

Radiation doses to mediastinal organs at risk in early-stage unfavorable Hodgkin lymphoma- a risk stratified analysis of the GHSG HD17 trial.

Introduction: The German Hodgkin Study Group (GHSG) HD17 trial established the omission of radiotherapy (RT) for patients with early-stage unfavorable Hodgkin lymphoma being PET-negative after 2 cycles of BEACOPP escalated plus 2 cycles of ABVD. This patient group reveals heterogeneity in characteristics and disease extent which prompted us to perform a decisive dosimetric analysis according to GHSG risk factors. This may help to tailor RT individually balancing risks and benefits. Methods: For quality assurance, RT-plans were requested from the treating facilities (n= 141) and analyzed centrally. Dose-volume histograms were scanned either paper-based or digitally to obtain doses to mediastinal organs. These were registered and compared according to GHSG risk factors. Results: Overall, RT plans of 176 patients were requested, 139 of which had dosimetric information on target volumes within the mediastinum. Most of these patients were stage II (92.8%), had no B-symptoms (79.1%) and were aged < 50 years (89.9%). Risk factors were present in 8.6% (extranodal involvement), 31.7% (bulky disease), 46.0% (elevated erythrocyte sedimentation rate) and 64.0% (three involved areas), respectively. The presence of bulky disease significantly affected the mean RT doses to the heart (p=0.005) and to the left lung (median: 11.3 Gy vs. 9.9 Gy; p=0.042) as well as V5 of the right and left lung, respectively (median right lung: 67.4% vs. 51.0%; p=0.011; median left lung: 65.9% vs. 54.2%; p=0.008). Significant differences in similar organs at risk parameters could be found between the sub-cohorts with the presence or absence of extranodal involvement, respectively. In contrast, an elevated erythrocyte sedimentation rate did not deteriorate dosimetry significantly. No association of any risk factor with radiation doses to the female breast was found. Conclusion: Pre-chemotherapy risk factors may help to predict potential RT exposure to normal organs and to critically review treatment indication. Individualized risk-benefit evaluations for patients with HL in early-stage unfavorable disease are mandatory.

Radiation Therapy in the German Hodgkin Study Group HD 16 and HD 17 Trials: Quality Assurance and Dosimetric Analysis for Hodgkin Lymphoma in the Modern Era.

Purpose: Radiation therapy (RT) is an integral part of treatment concepts for early-stage Hodgkin lymphoma. This analysis reports on RT quality in the recent HD16 and 17 trials of the German Hodgkin Study Group (GHSG). Methods and Materials: All RT plans of involved-node radiation therapy (INRT) in HD 17 were requested for analysis, along with 100 and 50 involved-field radiation therapy (IFRT) plans in HD 16 and 17, respectively. A structured assessment regarding field design and protocol adherence was performed by the reference radiation oncology panel of the GHSG. Results: Overall, 100 (HD 16) and 176 (HD 17) patients were eligible for analysis. In HD 16, 84% of RT series were evaluated as correct, with significant improvement compared with the predecessor studies (P < .001). In HD 17, 76.1% of INRT cases revealed a correct RT design compared with 69.0% of IFRT-cases, which was superior to previous studies (P < .001). Comparing INRT and IFRT, we found no significant differences in the percentage of any deviation (P = .418) or major deviations (P = .466). Regarding dosimetry, INRT was accompanied by an improvement in thyroid doses. Comparing different RT techniques, we found that intensity-modulated RT showed a reduction of high doses in the lung at the expense of an increased low-dose exposure in HD 17. Conclusions: The latest study generation of the GHSG demonstrates an improved quality in RT. A modern INRT design could be established without deterioration in quality. On a conceptual level, an individual consideration of the appropriate RT technique has to be performed.

Definition of an Normal Tissue Complication Probability Model for the Inner Ear in Definitive Radiochemotherapy of Nasopharynx Carcinoma.

Background: Definitive radiochemotherapy is the treatment of choice for locally advanced nasopharyngeal carcinoma. Due to the vicinity of the nasopharynx to the inner ear and the use of ototoxic platinum-based chemotherapy, there is a risk for irreversible damage to the auditory system. To avoid or minimize these critical side effects, radiation exposure to each inner ear must be balanced between target volume coverage and toxicity. However, normal tissue complication probability (NTCP) models of the inner ear validated by clinical data are rare. Patients and Methods: This retrospective study investigates the inner ear toxicity of 46 patients who received radio(chemo-)therapy for nasopharyngeal carcinoma at our institution from 2004 to 2021 according to CTCAE 5.0 criteria. For each inner ear, the mean (Dmean) and maximum (Dmax) dose in Gray (Gy) was evaluated and correlated with clinical toxicity data. Based on the data, an NTCP model and a cutoff dose logistic regression model (CDLR) were created. Results: In 11 patients (23.9%) hearing impairment and/or tinnitus was observed as a possible therapy-associated toxicity. Dmean was between 15−60 Gy, whereas Dmax was between 30−75 Gy. There was a dose-dependent, sigmoidal relation between inner ear dose and toxicity. A Dmean of 44 Gy and 65 Gy was associated with inner ear damage in 25% and 50% of patients, respectively. The maximum curve slope (m) was found at 50% and is m=0.013. The Dmax values showed a 25% and 50% complication probability at 58 Gy and 69 Gy, respectively, and a maximum slope of the sigmoid curve at 50% with m=0.025. Conclusion: There is a sigmoidal relation between radiation dose and incidence of inner ear toxicities. Dose constraints for the inner ear of <44 Gy (Dmean) or <58 Gy (Dmax) are suggested to limit the probability of inner ear toxicity <25%.

Late Sequelae of Radiotherapy­The Effect of Technical and Conceptual Innovations in Radiation Oncology.

BACKGROUND: Approximately half of all patients with tumors need radiotherapy. Long-term survivors may suffer from late sequelae of the treatment. The existing radiotherapeutic techniques are being refined so that radiation can be applied more precisely, with the goal of limiting the radiation exposure of normal tissue and reducing late sequelae. METHODS: This review is based on the findings of a selective search in PubMed for publications on late sequelae of conventional percutaneous radiotherapy, January 2000 to May 2020. Late sequelae affecting the central nervous system, lungs, and heart and the development of second tumors are presented, and radiobiological mechanisms and the relevant technical and conceptual considerations are discussed. RESULTS: The current standard of treatment involves the use of linear accelerators, intensity-modulated radiotherapy (IMRT), image-guided and respiratory-gated radiotherapy, and the integration of positron emission tomography combined with computed tomography (PET-CT) in radiation treatment planning. Cardiotoxicity has been reduced with regard to the risk of coronary heart disease after radiotherapy for Hodgkin's lymphoma (hazard ratio [HR] 0.44 [0.23; 0.85]). It was also found that the rate of radiation- induced pneumonitis dropped from 7.9% with conformal treatment to 3.5% with IMRT in a phase III lung cancer trial. It is hoped that neurocognitive functional impairment will be reduced by hippocampal avoidance in modern treatment planning: an initial phase III trial yielded a hazard ratio of 0.74 [0.58; 0.94]. It is estimated that 8% of second solid tumors in adults are induced by radiotherapy (3 additional tumors per 1000 patients at 10 years). CONCLUSION: Special challenges for research in this field arise from the long latency of radiation sequelae and the need for largescale, well-documented patient collectives in order to discern dose-effect relationships, and take account of cofactors, when the overall number of events is small. It is hoped that further technical and conceptual advances will be made in the areas of adaptive radiotherapy, proton and heavy-ion therapy, and personalized therapy.

The Lymph-Sparing Quotient: A Retrospective Risk Analysis on Extremity Radiation for Soft Tissue Sarcoma Treatment.

Radiation therapy (RT) for extremity soft tissue sarcoma is associated with lymphedema risk. In this study, we analyzed the influence of lymph-sparing volume on the lymphedema occurrence in patients who received adjuvant extremity RT. The lymph-sparing quotient (LSQ) was calculated by dividing the lymph-sparing volume by the total extremity volume with double weightingfor the narrowest lymph-sparing region. A total of 34 patients were enrolled in this analysis. The median applied total radiation dose was 66.3 Gy in 36 fractions. Acute lymphedema appeared in 12 patients (35%). Most of them (n = 8) were lymphedema grade 1 and five patients had grade 2 to 3 lymphedema. Chronic lymphedema appeared in 22 patients (65%). 17 of these patients had at least a grade 2 lymphedema. In 13 of 14 patients with an LSQ ≤ 0.2 and 11 of 20 patients with an LSQ > 0.2, an acute or chronic lymphedema ≥ grade 2 was observed. A Kaplan-Meier Analysis of the two groups with the endpoint of a two-year lymph edema-free survival (=2-YLEFS) was estimated with an univariate, significant result (2-YLEFS LSQ ≤ 0.2 vs. LSQ > 0.2: 0% vs. 39%; p = 0.006; hazard ratio LSQ ≤ 0.2 vs. > 0.2 2-YLEFS 2.822 (p = 0.013); 95% confidence interval (CI): 1.24-6.42). Maximizing the potential oncologically-justifiable lymph-sparing volume should be considered to reduce the risk of high-grade lymphedema when applying RT to extremities.

Biophysical Analysis of Acute and Late Toxicity of Radiotherapy in Gastric Marginal Zone Lymphoma-Impact of Radiation Dose and Planning Target Volume.

Successful studies on radiation therapy for gastric lymphoma led to a decrease in planning target volume (PTV) and radiation dose with low toxicities, maintaining excellent survival rates. It remains unclear as to which effects are to be expected concerning dose burden on organs at risk (OAR) by decrease in PTV vs. dose and whether a direct impact on toxicity might be expected. We evaluated 72 radiation plans, generated prospectively for a cohort of 18 patients who were treated for indolent gastric lymphoma in our department. As a prospective work, four radiation plans with different radiation doses and target volumes (40 Gy-involved field, 40 Gy-involved site, 30 Gy-involved field, 30 Gy-involved site) were generated for each patient. Mean dose burden on adjacent organs was compared between the planning groups. Cohort toxicity data served to estimate parameters for the Lyman-Kutcher-Burman (LKB) model for normal tissue complication probability (NTCP). These were used to anticipate adverse events for OAR. Literature parameters were used to estimate high-grade toxicities of OAR. Decrease of dose and/or PTV led to median dose reductions between 0.13 and 5.2 Gy, with a significant dose reduction on neighboring organs. Estimated model parameters for liver, spleen, and bowel toxicity were feasible to predict cohort toxicities. NTCP for the endpoints elevated liver enzymes, low platelet count, and diarrhea ranged between 15.9 and 22.8%, 27.6 and 32.4%, and 21.8 and 26.4% for the respective four plan variations. Field and dose reduction highly impact dose burden and NTCP for OAR during stomach radiation. Our estimated LKB model parameters offer a good approximation for low-grade toxicities in abdominal organs with modern radiation techniques.

Diagnostic efficiency of hybrid imaging using PSMA ligands, PET/CT, PET/MRI and MRI in identifying malignant prostate lesions.

OBJECTIVE: The objective of this study was to assess the accuracy of 68Ga-PSMA-11 PET/MRI, 18F-PSMA-1007 PET/CT, 68Ga-PSMA-11 PET/CT, and multiparametric (mp)MRI for the delineating of dominant intraprostatic lesions (IPL). MATERIALS AND METHODS: 35 patients with organ-confined prostate cancer who were assigned to definitive radiotherapy (RT) were divided into three groups based on imaging techniques: 68Ga-PSMA-PET/MRI (n = 9), 18F-PSMA-PET/CT (n = 16) and 68Ga-PSMA-PET/CT (n = 10). All patients without PSMA-PET/MRI received an additional mpMRI. PSMA-PET-based automatic isocontours and manual contours of the dominant IPLs were generated for each modality. The biopsy results were then used to validate whether any of the prostate biopsies were positive in the marked lesion using Dice similarity coefficient (DSC), Youden index (YI), sensitivity and specificity. Factors that can predict the accuracy of IPLs contouring were analysed. RESULTS: Diagnostic performance was significantly superior both for manual and automatic IPLs contouring using 68Ga-PSMA-PET/MRI (DSC/YI SUV70%-0.62/0.51), 18F-PSMA-PET/CT (DSC/YI SUV70%-0.67/0.53) or 68Ga-PSMA-PET/CT (DSC/YI SUV70%-0.63/0.51) compared to mpMRI (DSC/YI-0.47/0.41; p < 0.001). The accuracy for delineating IPLs was not improved by combination of PET/CT and mpMRI images compared to PET/CT alone. Significantly superior diagnostic accuracy was found for large prostate lesions (at least 15% from the prostate volume) and higher Gleason score (at least 7b) comparing to smaller lesions with lower GS. CONCLUSION: IPL localization was significantly improved when using PSMA-imaging procedures compared to mpMRI. No significant difference for delineating IPLs was found between hybrid method PSMA-PET/MRI and PSMA-PET/CT. PSMA-based imaging technique should be considered for the diagnostics of IPLs and focal treatment modality.

Radiotherapy as Part of Treatment Strategies in Nasal Cavity and Paranasal Sinus Malignancies.

BACKGROUND/AIM: Modern intensity-modulated radiotherapy (IMRT) is frequently applied to treat patients with nasal cavity and paranasal sinus (NC/PNS) malignancies. PATIENTS AND METHODS: One hundred and four patients who underwent radiotherapy (RT) between 1994 and 2020 were recognized. This analysis compared conventional-radiotherapy (CRT) and image-guided IMRT outcomes for NC/PNS malignancies. RESULTS: The median follow-up was 69 months. Eighty-eight patients (85%) were managed with image-guided IMRT. The median initial radiation dose was 65 Gy, with 68 Gy applied for patients treated with primary RT versus 63 Gy applied for adjuvant therapy (p=0.1). The 5-year locoregional control (LRC) was 85%. The locoregional recurrence rate was 18% following IMRT versus 31% in the 2D/3D-conventional RT group (p=0.09). Moreover, IMRT was associated with a lower inner-ear toxicity rate (8% vs. 20%, respectively; p=0.045). CONCLUSION: IMRT appears to be linked with higher LRC and lower inner-ear acute toxicities compared to conventional RT.

Impact of different radiation techniques and doses on cardiac implantable electronic devices.

BACKGROUND AND OBJECTIVE: Purpose of this investigation was to get deeper insight into the impact of different radiation techniques and doses on cardiac implantable electric devices (CIEDs). We aimed to mimic a worst-case scenario with very high doses and external radiation being applied directly on the devices. METHODS: Radiation was applied on 21 CIEDs as photon or electron therapy with maximum dose of 150Gy in fractions of 2 -20Gy. CIEDS were put directly into the beam. Brachytherapy was applied with doses of 6Gy to a maximum of 42Gy. Check-ups took place after every fraction and one week after radiation. We calculated the estimated potential risk for the health and survival of patients as well as the risk for CIEDs' loss of function. RESULTS: 28 life- or health-threatening errors occurred during photon therapy, 3/7 devices showed complete loss of function. During electron therapy, 31 potentially patient-threatening errors and 2 losses of function were detected. During brachytherapy, none of the devices showed loss of function but 8 patient-threatening errors occurred. Inadequate shock releases were mostly seen after photon and brachytherapy, random noises occurred more often during electron therapy. The earliest potentially serious error occurred during after 2Gy photon radiation and 6Gy brachytherapy. Losses of function occurred earliest at 80Gy. CONCLUSION: The results underline the warning for precaution concerning CIED patients derived from recommendations in the literature. Our study offers new information especially about the impact of electron radiation and brachytherapy on CIEDs. Risk for the devices to for loss of telemetry or battery capacity might be negligible with normafractionated therapy.

Toxicity Reduction after Craniospinal Irradiation via Helical Tomotherapy in Patients with Medulloblastoma: A Unicentric Retrospective Analysis.

Objectives: Recent trials with craniospinal irradiation (CSI) via helical Tomotherapy (HT) demonstrated encouraging medulloblastoma results. In this study, we assess the toxicity profile of different radiation techniques and estimate survival rates. Materials and Methods: We reviewed the records of 46 patients who underwent irradiation for medulloblastoma between 1999 and 2019 (27 conventional radiotherapy technique (CRT) and 19 HT). Patient, tumor, and treatment characteristics, as well as treatment outcomes-local control rate (LCR), event-free survival (EFS), and overall survival (OS)-were reviewed. Acute and late adverse events (AEs) were evaluated according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. Results: In total, 43 courses of CSI and three local RT were administered to the 46 patients: 30 were male, the median age was 7 years (range 1-56). A median total RT dose of 55 Gy (range 44-68) and a median CSI dose of 35 Gy (range, 23.4-40) was delivered. During follow-up (median, 99 months), six patients (13%) developed recurrence. The EFS rate after 5 years was 84%. The overall OS rates after 5 and 10 years were 95% and 88%, respectively. There were no treatment-related deaths. Following HT, a trend towards lower grade 2/3 acute upper gastrointestinal (p = 0.07) and subacute CNS (p = 0.05) toxicity rates was detected compared to CRT-group. The risk of late CNS toxicities, mainly grade 2/3, was significantly lower following HT technique (p = 0.003). Conclusion: CSI via HT is an efficacious treatment modality in medulloblastoma patients. In all, we detected a reduced rate of several acute, subacute, and chronic toxicities following HT compared to CRT.

Hybrid volumetric modulated arc therapy for hypofractionated radiotherapy of breast cancer: a treatment planning study.

PURPOSE: This study aims to evaluate the best possible practice using hybrid volumetric modulated arc therapy (H-VMAT) for hypofractionated radiation therapy of breast cancer. Different combinations of H­VMAT-a combination of three-dimensional radiotherapy (3D-CRT) and VMAT-were analyzed regarding planning target volume (PTV), dose coverage, and exposure to organs at risk (OAR). METHODS: Planning computed tomography scans were acquired in deep-inspiration breath-hold. A total of 520 treatment plans were calculated and evaluated for 40 patients, comprising six different H­VMAT plans and a 3D-CRT plan as reference. H­VMAT plans consisted of two treatment plans including 3D-CRT and VMAT. During H­VMAT planning, the use of hard wedge filters (HWF) and beam energies were varied. The reference plans were planned with mixed beam energies and the inclusion/omission of HWF. RESULTS: Compared to the reference treatment plans, all H­VMAT plans showed consistently better PTV dose coverage, conformity, and homogeneity. Additionally, OAR protection was significantly improved with several H­VMAT combinations (p < 0.05). The comparison of different H­VMAT combinations showed that inclusion of HWF in the base plan had a negative impact on PTV dose coverage, conformity, and OAR exposure. It also increased the planned monitor units and beam-on time. Advantages of using lower beam energies (6-MV photons) in both the base plan and in the VMAT supplementary dose were observed. CONCLUSION: The H­VMAT technique is an effective possibility for generating homogenous and conformal dose distributions. With the right choice of H­VMAT combination, superior OAR protection is achieved compared to 3D-CRT.

Impact of radiation techniques on lung toxicity in patients with mediastinal Hodgkin's lymphoma.

PURPOSE: Mediastinal radiotherapy (RT), especially when combined with bleomycin, may result in substantial pulmonary morbidity and mortality. The use of modern RT techniques like intensity-modulated radiotherapy (IMRT) is gaining interest to spare organs at risk. METHODS: We evaluated 27 patients who underwent RT for Hodgkin's lymphoma between 2009 and 2013 at our institution. For each patient, three different treatment plans for a 30-Gy involved-field RT (IFRT) were created (anterior-posterior-posterior-anterior setup [APPA], 5­field IMRT, and 7­field IMRT) and analyzed concerning their inherent "normal tissue complication probability" (NTCP) for pneumonitis and secondary pulmonary malignancy. RESULTS: The comparison of different radiation techniques showed a significant difference in favor of standard APPA (p < 0.01). The risk of lung toxicity was significantly higher in plans using 7­field IMRT than in plans using 5­field IMRT. The absolute juxtaposition showed an increase in risk for radiation pneumonitis of 1% for plans using 5­field IMRT over APPA according to QUANTEC (Quantitative Analyses of Normal Tissue Effects in the Clinic) parameters (Burman: 0.15%) and 2.6% when using 7­field IMRT over APPA (Burman: 0.7%) as well as 1.6% when using 7­field IMRT over 5­field IMRT (Burman: 0.6%). Further analysis showed an increase in risk for secondary pulmonary malignancies to be statistically significant (p < 0.01); mean induction probability for pulmonary malignoma was 0.1% higher in plans using 5­field IMRT than APPA and 0.19% higher in plans using 7­field IMRT than APPA as well as 0.09% higher in plans using 7­field IMRT than 5­field IMRT. During a median follow-up period of 65 months (95% confidence interval: 53.8-76.2 months), only one patient developed radiation-induced pneumonitis. No secondary pulmonary malignancies have been detected to date. CONCLUSION: Radiation-induced lung toxicity is rare after treatment for Hodgkin lymphoma but may be influenced significantly by the RT technique used. In this study, APPA RT plans demonstrated a decrease in potential radiation pneumonitis and pulmonary malignancies. Biological planning using NTCP may have the potential to define personalized RT strategies.

Comparison of virtual non-contrast dual-energy CT and a true non-contrast CT for contouring in radiotherapy of 3D printed lung tumour models in motion: a phantom study.

OBJECTIVES: This work aims to investigate whether virtual non-contrast (VNC) dual-energy CT(DECT) of contrasted lung tumours can be used as an alternative for true non-contrast (TNC) images in radiotherapy. Two DECT techniques and a TNC CT were compared and influences on gross tumour volume (GTV) volume and CT number from motion artefacts in three-dimensional printed lung tumour models (LTM) in amotion phantom were examined. METHODS: Two spherical LTMs (diameter 3.0 cm) with different inner shapes were created in a three-dimensional printer. The inner shapes contained water or iodine (concentration 5 mg ml-1) and were scanned with a dual-source DECT (ds-DECT), single-source sequential DECT (ss-DECT) and TNC CT in a respiratory motion phantom (15 breaths/min, amplitude 1.5 cm). CT number and volume of LTMs were measured. Therefore, two GTVs were contoured. RESULTS: Deviations in GTV volume (outer shape) of LTMs in motion for contrast-enhanced ss-DECT and ds-DECT VNC images compared to TNC images are not significant (p > 0.05). Relative GTV volume and CT number deviations (inner shapes) of LTMs in motion were 6.6 ± 0.6% and 104.4 ± 71.2 HU between ss-DECT and TNC CT and -8.4 ± 10.6% and 25.5 ± 58.5 HU between ds-DECT and TNC, respectively. CONCLUSION: ss-DECT VNC images could not sufficiently subtract iodine from water in LTMs inmotion, whereas ds-DECT VNC images might be a valid alternative to a TNC CT. ADVANCES IN KNOWLEDGE: ds-DECT provides a contrasted image for contouring and a non-contrasted image for radiotherapy treatment planning for LTM in motion.

Analyzing medical device connectivity and its effect on cyber security in german hospitals.

BACKGROUND: Modern healthcare devices can be connected to computer networks and many western healthcare institutions run those devices in networks. At the same time, cyber attacks are on the rise and there is evidence that cybercriminals do not spare critical infrastructure such as major hospitals, even if they endanger patients. Intuitively, the more and closer connected healthcare devices are to public networks, the higher the risk of getting attacked. METHODS: To asses the current connectivity status of healthcare devices, we surveyed the field of German hospitals and especially University Medical Center UMCs. RESULTS: The results show a strong correlation between the networking degree and the number of medical devices. The average number of medical devices is 25.150, with a median of networked medical devices of 3.600. Actual key users of networked medical devices are the departments Radiology, Intensive Care, Radio-Oncology RO, Nuclear Medicine NUC, and Anaesthesiology in the group of UMCs. In the next five years, the usage of networked medical devices will increase significantly in the departments of Surgery, Intensive Care, and Radiology. We detected a strong correlation between the degree of connectivity and the likelihood of being attacked.The survey answers regarding the cyber security status reveal a lack of security basics in some of the inquired hospitals. We did discover successful attacks in hospitals with separated or subsidiary departments. A fusion of competencies on an organizational level facilitates the right behavior here. Most hospitals rated themselves predominantly positively in the self-assessment but also stated the usefulness of IT security insurance. CONCLUSIONS: Concluding our results, hospitals are already facing the consequences of omitted measures within their growing pool of medical devices. Continuously relying on historically grown structures without adaption and trusting manufactures to solve vectors is a critical behavior that could seriously endanger patients.

Implementing a new scale for failure mode and effects analysis (FMEA) for risk analysis in a radiation oncology department.

PURPOSE: Patients and staffs are endangered by different failure modes during clinical routine in radiation oncology and risks are difficult to stratify. We implemented the method of failure mode and effects analysis (FMEA) via questionnaires in our institution and introduced an adapted scale applicable for radiation oncology. METHODS: Failure modes in physical treatment planning and daily routine were detected and stratified by ranking occurrence, severity, and detectability in a questionnaire. Multiplication of these values offers the risk priority number (RPN). We implemented an ordinal rating scale (ORS) as a combination of earlier published scales from the literature. This scale was optimized for German radiation oncology. We compared RPN using this ORS versus use of a rather subjective visual analogue rating scale (VRS). RESULTS: Mean RPN using ORS was 62.3 vs. 67.5 using VRS (p = 0.7). Use of ORS led to improved completeness of questionnaires (91 vs. 79%) and stronger agreement among the experts, especially concerning failure modes during radiation routine. The majority of interviewed experts found the analysis by using the ORS easier and expected a saving of time as well as higher intra- and interobserver reliability. CONCLUSION: The introduced rating scale together with a questionnaire survey provides merit for conducting FMEA in radiation oncology as results are comparable to the use of VRS and the process is facilitated.

Radiotherapy Dose and Volume De-escalation in Ocular Adnexal Lymphoma.

AIM: Modern radiotherapy (RT) technique and therapy de-escalation have led to encouraging results in lymphoma management. In this study, we aimed to describe the oncological and toxicity outcome in patients with ocular adnexal lymphoma. PATIENTS AND METHODS: A total of 45 patients with 52 orbital lesions who were treated at our Institution between 2003 and 2019 were considered. Clinical characteristics, treatment outcomes, and toxicity were assessed. Patients receiving 4-6 Gy were categorized as receiving ultra-low-dose RT, 24-30.6 Gy as standard-dose RT, and >30.6 Gy as high-dose RT. RESULTS: The predominant histological subtype was marginal zone lymphoma in 39 lesions (75%). Radiation dose ranged from 4-50.4 Gy. In the whole cohort, 11% of the lesions were treated with ultra-low-dose RT, 33% with standard-dose RT, and 56% with high-dose RT; 60% of lesions were treated using intensity-modulated RT (IMRT), while 44% of lesions were treated with partial orbital RT. The median duration of follow-up was 33 months. The overall response rate was 94% (complete response rate=83%). The 5-year local control rate, progression-free survival, and overall survival were 100%, 76%, and 92%, respectively. We did not detect any significant difference in progression-free or overall survival regarding different radiation doses and volumes. Ultra-low-dose RT was associated with a significantly lower rate of grade 2 late toxicities (0% vs. 6% and 31%, p=0.05) in comparison with standard-dose and high-dose RT, respectively. Patients who received IMRT had a significant fewer acute grade 2 (16% vs. 43%, p=0.05) and a trend towards lower late grade 2 toxicities (9% vs. 33%, p=0.06). CONCLUSION: Radiation dose and volume de-escalation seem to be safe and effective, with excellent local control and survival in the management of ocular adnexal lymphoma. IMRT seems to be associated with less toxicity.

The Role of Radiotherapy for Patients With Thyroid Cancer in the Modern Era.

BACKGROUND/AIM: Thyroid cancer (TC) is a relatively rare malignancy. The mainstay treatment is surgery followed by radioactive iodine (RAI) and medical systemic treatments. The role of external beam radiotherapy (EBRT) in TC is controversial regarding the survival benefits. The aim of this study was to analyse the effectiveness of EBRT for different forms of TC in different stages. PATIENTS AND METHODS: Between January 1990 and 2016, 75 patients underwent 255 radiotherapy (RT) courses at our Institution. Local control (LC) and progression-free survival (PFS) were analyzed. RESULTS: The cohort consisted of 22 patients who received curative RT and 53 patients who received RT in a palliative setting. The estimated 5-year LC for the curative group was 92±8% and the palliative group 78±7%. The estimated 5-year PFS for the curative group was 27±9% and for palliative group 31±6%. CONCLUSION: The addition of RT in TC seems to be safe and effective. Our analysis showed an excellent local control (median >15 years) regardless of the treatment setting.

A treatment planning study comparing IMRT techniques and cyber knife for stereotactic body radiotherapy of low-risk prostate carcinoma.

PURPOSE: Comparing radiation treatment plans by using the same safety margins and dose objectives for all techniques, to ascertain the optimal radiation technique for the stereotactic body radiotherapy (SBRT) of low-risk prostate cancer. MATERIAL AND METHODS: Treatment plans for 27 randomly selected patients were compared using intensity-modulated (IMRT) techniques as Sliding Window (SW), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT), as well as Cyber Knife (CK) system. The target dose was calculated to 36.25 Gy delivered in five fractions over 1 week. Dosimetric indices for target volume and organs at risk (OAR) as well as normal tissue complication probability (NTCP) of late rectal and urinary bladder toxicities were analyzed. RESULTS: The CK provided lower homogeneity in the target volume, but higher values for most of the conformity indices compared to the IMRT approaches. The SW demonstrated superior rectum sparing at medium-to-high dose range (V18 Gy - V32.6 Gy) compared to other techniques (p < 0.05). The whole urinary bladder experienced the best shielding by SW and VMAT at the medium dose (V18 Gy, p < 0.05 versus CK), however we obtained no relevant differences between techniques at the high dose. Generally, the CK demonstrated significantly superior rectum and bladder exposure at V18 Gy as compared to HT, SW, and VMAT. For the rectum, mean NTCP values were significantly superior for HT (NTCP = 2.3%, p < 0.05), and for urinary bladder, the NTCP showed no significant advantages for any technique. CONCLUSION: No absolute dosimetric advantage was revealed to choose between CK or IMRT techniques for the SBRT of low-grade prostate cancer. Using the same safety margins and dose objectives, IMRT techniques demonstrated superior sparing of the rectum and bladder at a medium dose compared to CK. Comparing different IMRT approaches SW displayed superior rectum sparing at a medium-to-high dose range, whereas both SW and RA revealed superior bladder sparing compared to HT. HT demonstrated a significantly lower NTCP outcome compared to CK or IMRT techniques regarding the rectum. Radiation plans can be optimized further by an individual modification of dose objectives independent of the treatment plan strategy.