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.

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.

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.

Radiotherapy for extramedullary leukaemic manifestation (Chloroma).

PURPOSE: Extramedullary leukaemic disease (EMD, synonym chloroma) is a rare solid manifestation of myeloid leukaemia for which the value of radiotherapy (RT) as a treatment strategy remains controversial. The aim of this study is to analyse the effectiveness of various RT doses for EMD in the modern treatment era. MATERIALS AND METHODS: Between January 2000 and June 2016, 20 patients with total of 45 lesions underwent RT for EMD at our institution. RESULTS: With a median radiation dose of 26 Gy (range 4-42 Gy), local remission could be achieved in 91% of patients (complete remission rate: 71%). The median duration of local control (DOLC) was 17 months (95% confidence interval [CI] 0.5-33) and the median overall survival (OS) after chloroma onset was 24 months (95% CI 11-38). No noticeable difference between high- and low-dose regimens has been observed (74% versus 68%; P = 0.5). In the multivariate analysis, only Eastern Cooperative Oncology Group (ECOG) score and bone marrow state during RT have proven to be determinant for durable local control and OS. CONCLUSIONS: Low-dose RT (≤26 Gy) achieves good local control compared to high-dose regimes. Bone marrow state during RT and ECOG score during RT may play a crucial role, influencing both DOLC and OS.

A treatment planning study of prone vs. supine positions for locally advanced rectal carcinoma : Comparison of 3­dimensional conformal radiotherapy, tomotherapy, volumetric modulated arc therapy, and intensity-modulated radiotherapy.

PURPOSE: To ascertain the optimal radiation technique and radiation position for the neoadjuvant radiotherapy of patients with rectal cancer. MATERIALS AND METHODS: Treatment plans with similar dose objectives were generated for 20 selected patients. Dosimetric comparison was performed between prone and supine positions and between different radiation techniques. Dosimetric indices for the target volume and organs at risk (OAR) as well as normal tissue complication probability (NTCP) of late small bowel toxicity were analyzed. RESULTS: The helical tomotherapy (HT) in the prone position provided the optimal dose homogeneity in the target volume with the value of 0. Superior conformity values were obtained for Sliding Window (SW), Rapid Arc (RA) and HT compared to three-dimensional conformal radiotherapy (3D-CRT) techniques. All of the techniques showed dose reduction to OAR in the high-dose area in prone position versus supine position. Pairwise comparison revealed significantly higher small bowel protection by RA in the prone position in the high-dose area (V75, V45Gy). Similarly, superior bladder sparing was found for 3D-CRT in the prone position at higher doses (V50, V75). More healthy tissue in the radiation volume was involved by application of 3D-CRT with no relevant difference between positions. The mean values of NTCP for the small bowel did not show clinically meaningful variation between the techniques. CONCLUSION: All techniques provided superior sparing of OAR in the prone position. At higher radiation doses, treatment in prone position resulted in significant OAR protection, especially concerning small bowel sparing by RA and bladder sparing by 3D CRT.

Treatment planning for spinal radiosurgery : A competitive multiplatform benchmark challenge.

PURPOSE: To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual's planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches. METHODS: Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system. RESULTS: All 12 centers could reach equality (n = 4) or outperform (n = 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p = 0.002). CONCLUSIONS: High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.

Post-transplant lymphoproliferative disorder in the pelvis successfully treated with consolidative radiotherapy.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLDs) are aggressive malignancies which represent one of the major post-transplant complications. However, treatment options vary significantly and localized disease may be curatively treated with radiotherapy (RT) or surgery. We report a case of recurrent rectal PTLD, which was successfully treated by chemoimmunotherapy followed by RT. CASE PRESENTATION: We describe a patient who developed a rectal lymphoproliferative lesion 11 years after kidney transplant, which was successfully treated with consolidative RT using 25.4 Gy sequential to chemoimmunotherapy (R-CHOP). RT was well tolerated and the patient showed no signs of grade 3 or 4 toxicity. This patient is free of recurrence 52 months after RT, with an overall survival of 62 months since diagnosis. CONCLUSION: Conventionally fractionated moderate-dose RT appears to be a tolerable and effective treatment option for localized PTLD if a sufficient systemic treatment cannot be applied.

Low-dose total skin electron beam therapy for cutaneous lymphoma : Minimal risk of acute toxicities.

BACKGROUND: Low-dose total skin electron beam therapy (TSEBT) is attracting increased interest for the effective palliative treatment of primary cutaneous T­cell lymphoma (pCTCL). In this study, we compared toxicity profiles following various radiation doses. PATIENTS AND METHODS: We reviewed the records of 60 patients who underwent TSEBT for pCTCL between 2000 and 2016 at the University Hospital of Munster. The treatment characteristics of the radiotherapy (RT) regimens and adverse events (AEs) were then analyzed and compared. RESULTS: In total, 67 courses of TSEBT were administered to 60 patients. Of these patients, 34 (51%) received a standard dose with a median surface dose of 30 Gy and 33 patients (49%) received a low dose with the median surface dose of 12 Gy (7 salvage low-dose TSEBT courses were administered to 5 patients). After a median follow-up of 15 months, the overall AE rate was 100%, including 38 patients (57%) with grade 2 and 7 (10%) with grade 3 AEs. Patients treated with low-dose TSEBT had significantly fewer grade 2 AEs than those with conventional dose regimens (33 vs. 79%, P < 0.001). A lower grade 3 AE rate was also observed in patients who had received the low-dose regimen compared to those with the conventional dose regimens (6 vs. 15%, P = 0.78). Multiple/salvage low-dose TSEBT courses were not associated with an increased risk of acute AEs. CONCLUSION: Low-dose TSEBT regimens are associated with significantly fewer grade 2 acute toxicities compared with conventional doses of TSEBT. Repeated/Salvage low-dose TSEBT, however, appears to be tolerable and can even be applied safely in patients with cutaneous relapses.

Planning benchmark study for SBRT of early stage NSCLC : Results of the DEGRO Working Group Stereotactic Radiotherapy.

PURPOSE: The aim was to evaluate stereotactic body radiation therapy (SBRT) treatment planning variability for early stage nonsmall cell lung cancer (NSCLC) with respect to the published guidelines of the Stereotactic Radiotherapy Working Group of the German Society for Radiation Oncology (DEGRO). MATERIALS AND METHODS: Planning computed tomography (CT) scan and the structure sets (planning target volume, PTV; organs at risk, OARs) of 3 patients with early stage NSCLC were sent to 22 radiotherapy departments with SBRT experience: each department was asked to prepare a treatment plan according to the DEGRO guidelines. The prescription dose was 3 fractions of 15 Gy to the 65% isodose. RESULTS: In all, 87 plans were generated: 36 used intensity-modulated arc therapy (IMAT), 21 used three-dimensional conformal radiation therapy (3DCRT), 6 used static field intensity-modulated radiation therapy (SF-IMRT), 9 used helical radiotherapy and 15 used robotic radiosurgery. PTV dose coverage and simultaneously kept OARs doses were within the clinical limits published in the DEGRO guidelines. However, mean PTV dose (mean 58.0 Gy, range 52.8-66.4 Gy) and dose conformity indices (mean 0.75, range 0.60-1.00) varied between institutions and techniques (p ≤ 0.02). OARs doses varied substantially between institutions, but appeared to be technique independent (p = 0.21). CONCLUSION: All studied treatment techniques are well suited for SBRT of early stage NSCLC according to the DEGRO guidelines. Homogenization of SBRT practice in Germany is possible through the guidelines; however, detailed treatment plan characteristics varied between techniques and institutions and further homogenization is warranted in future studies and recommendations. Optimized treatment planning should always follow the ALARA (as low as reasonably achievable) principle.

4D-Listmode-PET-CT and 4D-CT for optimizing PTV margins in gastric lymphoma : Determination of intra- and interfractional gastric motion.

PURPOSE: New imaging protocols for radiotherapy in localized gastric lymphoma were evaluated to optimize planning target volume (PTV) margin and determine intra-/interfractional variation of the stomach. METHODS: Imaging of 6 patients was explored prospectively. Intensity-modulated radiotherapy (IMRT) planning was based on 4D/3D imaging of computed tomography (CT) and positron-emission tomography (PET)-CT. Static and motion gross tumor volume (sGTV and mGTV, respectively) were distinguished by defining GTV (empty stomach), clinical target volume (CTV = GTV + 5 mm margin), PTV (GTV + 10/15/20/25 mm margins) plus paraaortic lymph nodes and proximal duodenum. Overlap of 4D-Listmode-PET-based mCTV with 3D-CT-based PTV (increasing margins) and V95/D95 of mCTV were evaluated. Gastric shifts were determined using online cone-beam CT. Dose contribution to organs at risk was assessed. RESULTS: The 4D data demonstrate considerable intra-/interfractional variation of the stomach, especially along the vertical axis. Conventional 3D-CT planning utilizing advancing PTV margins of 10/15/20/25 mm resulted in rising dose coverage of mCTV (4D-Listmode-PET-Summation-CT) and rising D95 and V95 of mCTV. A PTV margin of 15 mm was adequate in 3 of 6 patients, a PTV margin of 20 mm was adequate in 4 of 6 patients, and a PTV margin of 25 mm was adequate in 5 of 6 patients. CONCLUSION: IMRT planning based on 4D-PET-CT/4D-CT together with online cone-beam CT is advisable to individualize the PTV margin and optimize target coverage in gastric lymphoma.

Cone-beam CT-guided radiotherapy in the management of lung cancer: Diagnostic and therapeutic value.

BACKGROUND: Recent studies have demonstrated an increase in the necessity of adaptive planning over the course of lung cancer radiation therapy (RT) treatment. In this study, we evaluated intrathoracic changes detected by cone-beam CT (CBCT) in lung cancer patients during RT. METHODS AND MATERIALS: A total of 71 lung cancer patients treated with fractionated CBCT-guided RT were evaluated. Intrathoracic changes and plan adaptation priority (AP) scores were compared between small cell lung cancer (SCLC, n = 13) and non-small cell lung cancer (NSCLC, n = 58) patients. RESULTS: The median cumulative radiation dose administered was 54 Gy (range 30-72 Gy) and the median fraction dose was 1.8 Gy (range 1.8-3.0 Gy). All patients were subjected to a CBCT scan at least weekly (range 1-5/week). We observed intrathoracic changes in 83 % of the patients over the course of RT [58 % (41/71) regression, 17 % (12/71) progression, 20 % (14/71) atelectasis, 25 % (18/71) pleural effusion, 13 % (9/71) infiltrative changes, and 10 % (7/71) anatomical shift]. Nearly half, 45 % (32/71), of the patients had one intrathoracic soft tissue change, 22.5 % (16/71) had two, and three or more changes were observed in 15.5 % (11/71) of the patients. Plan modifications were performed in 60 % (43/71) of the patients. Visual volume reduction did correlate with the number of CBCT scans acquired (r = 0.313, p = 0.046) and with the timing of chemotherapy administration (r = 0.385, p = 0.013). CONCLUSION: Weekly CBCT monitoring provides an adaptation advantage in patients with lung cancer. In this study, the monitoring allowed for plan adaptations due to tumor volume changes and to other anatomical changes.

Long-term survival following additive radiotherapy in patients with atypical teratoid rhabdoid tumors.

BACKGROUND: Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive disease of embryonic origin accounting for <5% of all pediatric central nervous system (CNS) tumors. PATIENTS AND METHODS: We describe a series of five cases of CNS ATRT. The first three patients underwent subtotal tumor resection. Gross total resection of the tumor was achieved in the fourth and fifth patients. Only 4 patients received chemotherapy, whereas all 5 patients received additive radiotherapy (RT). The latter included three dimensional (3D) conformal RT or intensity modulated RT (IMRT) with a median dose of 54 Gy (range 50.4-59.0 Gy) applied in daily fractions of 1.8 Gy. The median interval between surgery and RT was 5 months (range 2-11 months). RESULTS: Two months after completion of RT, 4 patients had achieved complete radiologic remission. The median event-free survival period was 46 months (range 10-90 months). However, the first patient died 17 months after developing an out-of-field recurrence. The third patient developed a recurrence 11 months after salvage RT. The other 3 patients (cases 2, 4, and 5) remain alive with no evidence of disease 59, 46 and 90 months after therapy, respectively. CONCLUSION: Overall, the 5 patients survived for a median of 48 months (range 25-90 months) from the time of initial diagnosis and they tolerated the RT well, without severe acute or late onset toxicities. The results imply a potential survival gain after irradiation at acceptable toxicity level.

Breath-hold technique in conventional APPA or intensity-modulated radiotherapy for Hodgkin's lymphoma: Comparison of ILROG IS-RT and the GHSG IF-RT.

INTRODUCTION: The present study addresses the role of intensity-modulated radiotherapy (IMRT) in contrast to standard RT (APPA) for patients with Hodgkin's lymphoma (HL) with a focus on deep inspiration breath-hold (DIBH) technique and a comparison between the International Lymphoma Radiation Oncology Group (ILROG) Involved Site Radiotherapy (IS-RT) versus the German Hodgkin Study Group (GHSG) Involved Field Radiotherapy (IF-RT). METHODS: APPA treatment and 2 IMRT plans were compared for 11 patients with HL. Furthermore, treatment with DIBH versus free breathing (FB) and two different treatment volumes, i.e. IF-RT versus IS-RT, were compared. IMRT was planned as a sliding-window technique with 5 and 7 beam angles. For each patient 12 different treatment plans were calculated (132 plans). Following organs at risk (OAR) were analysed: lung, heart, spinal cord, oesophagus, female breast and skin. Comparisons of the different values with regard to dose-volume histograms (DVH), conformity and homogeneity indices were made. RESULTS: IS-RT reduces treatment volumes. With respect to the planning target volume (PTV), IMRT achieves better conformity but the same homogeneity. Regarding the D mean for the lung, IMRT shows increased doses, while RT in DIBH reduces doses. The IMRT shows improved values for Dmax concerning the spinal cord, whereas the APPA shows an improved D mean of the lung and the female breast. CONCLUSION: IS-RT reduces treatment volumes. Intensity-modulated radiotherapy shows advantages in the conformity. Treatment in DIBH also reduces the dose applied to the lungs and the heart.

Treatment of folliculitis decalvans using intensity-modulated radiation via tomotherapy.

BACKGROUND: Folliculitis decalvans (FD) is a form of primary neutrophilic scarring alopecia that is characterized clinically by chronic suppurative folliculitis and often associated with pruritus or even pain. Treatment of FD is often difficult. Herein, we report a case of recalcitrant and painful folliculitis decalvans refractory to antibiotic and anti-inflammatory therapies, which was successfully treated by intensity-modulated radiotherapy (IMRT) in order to irreversibly eliminate hair follicles that prove to be one etiological trigger. CASE PRESENTATION: A 45-year-old male patient with a refractory FD presented with a crusting suppurative folliculitis and atrophic scarring patches on the scalp associated with pain and pruritus. We attempted relief of symptoms by reducing scalp inflammation and eliminating hair follicles through radiation. We delivered 11.0 Gy in two radiation series using tomotherapy, 5.0 Gy in 5 equivalent fractions as a first radiation course. The symptoms markedly decreased but did not totally disappear. Therefore, we delivered a second radiation series 4 months later with an additional 6 Gy. This led to almost complete epilation on the scalp and abolished pain and pruritus on the capillitium. The patient was regularly followed up until 26 months after radiotherapy. Draining lesions or exudation did not recur. He only experienced discrete hair regrowth in the occipital region with folliculitis 12 months after radiotherapy. These residual lesions are currently treated with laser epilation therapy. CONCLUSION: A radical approach to eliminating hair follicles by repeated radiation therapy may induce lasting relief of symptoms in chronic suppurative FD associated with persistent trichodynia.

Optimization by visualization of indices.

BACKGROUND AND PURPOSE: Physical 3D treatment planning provides a pool of parameters describing dose distributions. It is often useful to define conformal indices to enable quicker evaluation. However, the application of individual indices is controversial and not always effective. The aim of this study was to design a quick check of dose distributions based on several indices detecting underdosages within planning target volumes (PTVs) and overdosages in normal tissue. MATERIALS AND METHODS: Dose distributions of 215 cancer patients were considered. Treatment modalities used were three-dimensional conformal radiotherapy (3DCRT), radiosurgery, intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (IMAT) and tomotherapy. The volumes recommended in ICRU 50 and 83 were used for planning and six conformation and homogeneity indices were selected: CI, CN, CICRU, COV, C∆, and HI. These were based on the PTV, the partial volume covered by the prescribed isodose (PI; PTVPI), the treated volume (TVPI), near maximum D2 and near minimum D98. Results were presented as a hexagon-the corners of which represent the values of the indices-and a modified test function F (Rosenbrock's function) was calculated. Results refer to clinical examples and mean values, in order to allow evaluation of the power of F and hexagon-based decision support procedures in detail and in general. RESULTS: IMAT and tomotherapy showed the best values for the indices and the lowest standard deviation followed by static IMRT. DCRT and radiosurgery (e.g. CN: IMAT 0.85 ± 0.06; tomotherapy 0.84 ± 0.06; IMRT 0.83 ± 0.07; 3DCRT 0.65 ± 0.08; radiosurgery 0.64 ± 0.11). In extreme situations, not all indices reflected the situation correctly. Over- and underdosing of PTV and normal tissue could be qualitatively assessed from the distortion of the hexagon in graphic analysis. Tomotherapy, IMRT, IMAT, 3DCRT and radiosurgery showed increasingly distorted hexagons, the type of distortion indicating exposure of normal tissue volumes. The calculated F values correlated with these observations. CONCLUSION: An evaluation of dose distributions cannot be based on a single conformal index. A solution could be the use of several indices presented as a hexagonal graphic and/or as a test function.

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.

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.

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 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.