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.

Reduction of tumor volume during radiotherapy in patients with small-cell lung cancer and its prognostic significance.

BACKGROUND: Several studies have reported the potential prognostic significance of tumor volume reduction ratio (VRR) induced by radiotherapy (RT) in patients with non-small-cell lung cancer. However, there are no data yet on the prognostic significance of volumetric shrinkage in patients with small-cell lung cancer (SCLC). This study aimed to demonstrate the correlation between tumor volume reduction ratio and treatment outcomes. MATERIALS AND METHODS: The study included 61 patients with SCLC treated with fractionated RT of the primary tumor at our institution between 2013 and 2020. The relationship between volumetric changes in gross tumor volume (GTV) during radiotherapy and outcomes were analyzed and reported. RESULTS: The median radiation dose was 59.4 Gy (median fraction dose was 1.8 Gy). The median GTV before radiotherapy was 74 cm3, with a median GTV reduction of 48%. There was a higher VRR in patients receiving concurrent radiochemotherapy (p = 0.05). No volumetric parameters were identified as relevant predictors of outcome in the entire cohort. In multivariate analysis, only age had an impact on survival, while prophylactic whole-brain radiation influenced the progression-free survival significantly. CONCLUSION: Concurrent chemotherapy was associated with a higher VRR than sequential chemotherapy. No significant impact of VRR on patients' outcome or survival was detected.

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.

Impact of dose escalation on colostomy-free survival and treatment outcome in squamous cell anal carcinoma.

PURPOSE: Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose escalation on colostomy-free survival (CFS), overall survival (OS), locoregional control (LRC), progression-free survival (PFS), and acute and late toxicities in patients with squamous cell anal cancer. METHODS: Considered were the outcomes of 87 patients with anal cancer treated with radiation/RCT between May 2004 and January 2020 at our institution. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0). RESULTS: The 87 patients received treatment with a median boost of 63 Gy to the primary tumor. With a median follow-up of 32 months, the 3­year CFS, OS, LRC, and PFS were 79.5%, 71.4%, 83.9%, and 78.5%, respectively. Tumor relapse occurred in 13 patients (14.9%). Dose escalation to > 63 Gy (maximum 66.6 Gy) to the primary tumor in 38/87 patients revealed a nonsignificant trend for improved 3­year CFS (82.4% vs. 97%, P = 0.092), a significantly improved CFS for T2/T3 tumors (72.6% vs. 100%, P = 0.008), and a significantly improved 3­year PFS for T1/T2 tumors (76.7% vs. 100%, P = 0.035). While acute toxicities did not differ, dose escalation > 63 Gy led to a higher rate of chronic skin toxicities (43.8% vs. 69%, P = 0.042). Treatment with intensity-modulated radiotherapy (IMRT) showed a significant improvement in 3­year OS (75.4% vs. 53.8%, P = 0.048). In multivariate analysis, significant improvements for T1/T2 tumors (CFS, OS, LRC, PFS), G1/2 tumors (PFS), and IMRT (OS) were shown. The nonsignificant trend for CFS improvement with dose escalation > 63 Gy was also apparent in multivariate analysis (P = 0.067). CONCLUSION: Dose escalation > 63 Gy (maximum 66.6 Gy) may improve CFS and PFS for certain subgroups, with a concomitant increase in chronic skin toxicities. Modern IMRT seems to be associated with an improvement in OS.

Efficacy of Multimodality Approach in Patients With Recurrent Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) is characterized by high relapse rates and low survival in comparison to other malignancies. PATIENTS AND METHODS: Fifty-two patients suffering from recurrent HNSCC were compared, analyzing the impact of different regimes, including surgery, radiotherapy (RT), chemotherapy and immunotherapy on progression-free survival (PFS), overall survival (OS), locoregional control (LRC), and adverse events. RESULTS: The standard RT technique was intensity-modulated radiotherapy (IMRT) in all patients. In the multivariate analysis, higher cumulative RT dose significantly influenced LRC whereas surgery and age significantly impacted PFS and OS. CONCLUSION: IMRT dose-escalation, as well as surgery, appear beneficial in the treatment of recurrent HNSCC. Moreover, nivolumab and platin-based therapy might be superior agents for systemic therapy in comparison to cetuximab.

Risk management patterns in radiation oncology-results of a national survey within the framework of the Patient Safety in German Radiation Oncology (PaSaGeRO) project.

PURPOSE: Risk management (RM) is a key component of patient safety in radiation oncology (RO). We investigated current approaches on RM in German RO within the framework of the Patient Safety in German Radiation Oncology (PaSaGeRO) project. Aim was not only to evaluate a status quo of RM purposes but furthermore to discover challenges for sustainable RM that should be addressed in future research and recommendations. METHODS: An online survey was conducted from June to August 2021, consisting of 18 items on prospective and reactive RM, protagonists of RM, and self-assessment concerning RM. The survey was designed using LimeSurvey and invitations were sent by e­mail. Answers were requested once per institution. RESULTS: In all, 48 completed questionnaires from university hospitals, general and non-academic hospitals, and private practices were received and considered for evaluation. Prospective and reactive RM was commonly conducted within interprofessional teams; 88% of all institutions performed prospective risk analyses. Most institutions (71%) reported incidents or near-events using multiple reporting systems. Results were presented to the team in 71% for prospective analyses and 85% for analyses of incidents. Risk conferences take place in 46% of institutions. 42% nominated a manager/committee for RM. Knowledge concerning RM was mostly rated "satisfying" (44%). However, 65% of all institutions require more information about RM by professional societies. CONCLUSION: Our results revealed heterogeneous patterns of RM in RO departments, although most departments adhered to common recommendations. Identified mismatches between recommendations and implementation of RM provide baseline data for future research and support definition of teaching content.

Development of Organ-Preserving Radiation Therapy in Gastric Marginal Zone Lymphoma.

Gastric marginal zone lymphoma (gMZL) of mucosa-associated lymphoid tissue (MALT) may persist even after H. pylori eradication, or it can be primarily Helicobacter pylori (H. pylori) independent. For patients without the successful eradication of lymphoma, or with progressive disease, treatment options have historically included partial or total gastrectomy. Presently, in these instances, curative radiation therapy (RT) is the current standard of care. This review emphasizes the historically changing role of radiation therapy in gMZL, progressing from large-volume RT without surgery, to localized RT, on its own, as a curative organ-preserving treatment. This overview shows the substantial progress in radiation therapy during the recent two to three decades, from high-dose, large-field techniques to low-dose, localized target volumes based on advanced imaging, three-dimensional treatment planning, and advanced treatment delivery techniques. RT has evolved from very large extended field techniques (EF) with prophylactic treatment of the whole abdomen and the supradiaphragmatic lymph nodes, applying doses between 30 and 50 Gy, to involved-field RT (IF), to the current internationally recommended involved site radiation therapy (ISRT) with a radiation dose of 24-30 Gy in gMZL. Stage-adapted RT is a highly effective and safe treatment with excellent overall survival rates and very rare acute or late treatment-related toxicities, as shown not only in retrospective studies, but also in large prospective multicenter studies, such as those conducted by the German Study Group on Gastrointestinal Lymphoma (DSGL). Further de-escalation of the radiation treatments with low-dose 20 Gy, as well as ultra-low-dose 4 Gy radiation therapy, is under investigation within ongoing prospective clinical trials of the International Lymphoma Radiation Oncology Group (ILROG) and of the German Lymphoma Alliance (GLA).

Impact of Adjuvant Radiotherapy in Patients with Central Neurocytoma: A Multicentric International Analysis.

BACKGROUND: Central neurocytoma (CN) is a rare tumor accounting for <0.5% of all intracranial tumors. Surgery ± radiotherapy is the mainstay treatment. This international multicentric study aims to evaluate the outcomes of CNs patients after multimodal therapies and identify predictive factors. PATIENTS AND METHODS: We retrospectively identified 33 patients with CN treated between 2005 and 2019. Treatment characteristics and outcomes were assessed. RESULTS: All patients with CN underwent surgical resection. Radiotherapy was delivered in 19 patients. The median radiation dose was 54 Gy (range, 50-60 Gy). The median follow-up time was 56 months. The 5-year OS and 5-year PFS were 90% and 76%, respectively. Patients who received radiotherapy had a significantly longer PFS than patients without RT (p = 0.004) and a trend towards longer OS. In addition, complete response after treatments was associated with longer PFS (p = 0.07). CONCLUSIONS: Using RT seems to be associated with longer survival rates with an acceptable toxicity profile.

Pulmonary Toxicity after Total Body Irradiation-An Underrated Complication? Estimation of Risk via Normal Tissue Complication Probability Calculations and Correlation with Clinical Data.

Total body irradiation (TBI) is an essential part of various conditioning regimens prior to allogeneic stem cell transplantation, but is accompanied by relevant (long-term) toxicities. In the lungs, a complex mechanism induces initial inflammation (pneumonitis) followed by chronic fibrosis. The hereby presented analysis investigates the occurrence of pulmonary toxicity in a large patient collective and correlates it with data derived from normal tissue complication probability (NTCP) calculations. The clinical data of 335 hemato-oncological patients undergoing TBI were analyzed with a follow-up of 85 months. Overall, 24.8% of all patients displayed lung toxicities, predominantly pneumonia and pulmonary obstructions (13.4% and 6.0%, respectively). NTCP calculations estimated median risks to be 20.3%, 0.6% and 20.4% for overall pneumonitis (both radiological and clinical), symptomatic pneumonitis and lung fibrosis, respectively. These numbers are consistent with real-world data from the literature and further specify radiological and clinical apparent toxicity rates. Overall, the estimated risk for clinical apparent pneumonitis is very low, corresponding to the probability of non-infectious acute respiratory distress syndrome, although the underlying pathophysiology is not identical. Radiological pneumonitis and lung fibrosis are expected to be more common but require a more precise documentation by the transplantation team, radiologists and radiation oncologists.

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.

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.

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.

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.

Impact of radiation technique, radiation fraction dose, and total cisplatin dose on hearing : Retrospective analysis of 29 medulloblastoma patients.

PURPOSE: To analyze the incidence and degree of sensorineural hearing loss (SNHL) resulting from different radiation techniques, fractionation dose, mean cochlear radiation dose (Dmean), and total cisplatin dose. MATERIAL AND METHODS: In all, 29 children with medulloblastoma (58 ears) with subclinical pretreatment hearing thresholds participated. Radiotherapy (RT) and cisplatin had been applied sequentially according to the HIT MED Guidance. Audiological outcomes up to the latest follow-up (median 2.6 years) were compared. RESULTS: Bilateral high-frequency SNHL was observed in 26 patients (90%). No significant differences were found in mean hearing threshold between left and right ears at any frequency. A significantly better audiological outcome (p < 0.05) was found after tomotherapy at the 6 kHz bone-conduction threshold (BCT) and left-sided 8 kHz air-conduction threshold (ACT) than after a combined radiotherapy technique (CT). Fraction dose was not found to have any impact on the incidence, degree, and time-to-onset of SNHL. Patients treated with CT had a greater risk of SNHL at high frequencies than tomotherapy patients even though Dmean was similar. Increase in severity of SNHL was seen when the total cisplatin dose reached above 210 mg/m2, with the highest abnormal level found 8-12 months after RT regardless of radiation technique or fraction dose. CONCLUSION: The cochlear radiation dose should be kept as low as possible in patients who receive simultaneous cisplatin-based chemotherapy. The risk of clinically relevant HL was shown when Dmean exceeds 45 Gy independent of radiation technique or radiation regime. Cisplatin ototoxicity was shown to have a dose-dependent effect on bilateral SNHL, which was more pronounced in higher frequencies.

A treatment planning study comparing tomotherapy, volumetric modulated arc therapy, Sliding Window and proton therapy for low-risk prostate carcinoma.

BACKGROUND: Comparing radiation treatment plans to ascertain the optimal intensity-modulated radiation technique for low-risk prostate cancer. METHODS: Treatment plans for 20 randomly selected patients were generated using the same dose objectives. A dosimetric comparison was performed between various intensity-modulated techniques, including protons. All treatment plans provided conventional treatment with 79.2Gy. Dosimetric indices for the target volume and organs at risk (OAR), including homogeneity index and four conformity indices were analyzed. RESULTS: No statistically significant differences between techniques were observed for homogeneity values. Dose distributions showed significant differences at low-to-medium doses. At doses above 50Gy all techniques revealed a steep dose gradient outside the planning target volume (PTV). Protons demonstrated superior rectum sparing at low-to-higher doses (V10-V70, P < .05) and bladder sparing at low-to-medium doses (V10-V30, P < .05). Helical tomotherapy (HT) provided superior rectum sparing compared to Sliding Window (SW) and Rapid Arc (RA) (V10-V70, P < .05). SW displayed superior bladder sparing compared to HT and RA (V10-V50, P < .05). Protons generated significantly higher femoral heads exposure and HT had superior sparing of those. CONCLUSION: All techniques are able to provide a homogeneous and highly conformal dose distribution. Protons demonstrated superior sparing of the rectum and bladder at a wide dose spectrum. The radiation technique itself as well as treatment planning algorithms result in different OAR sparing between HT, SW and RA, with superior rectum sparing by HT and superior bladder sparing by SW. Radiation plans can be further optimized by individual modification of dose objectives dependent on treatment plan strategy.