Uwe Haverkamp

Background/Objectives: The actual daily dose distribution during image-guided radiotherapy (IGRT) for prostate cancer (PCa) deviates from the planned due to positional and volumetric changes in the patient’s body and organs at risk (OAR). This study investigates the difference between planned and delivered dose, by calculating the actual daily dose to bladder and rectum for each radiotherapy fraction. The impact of OAR volumes on dose distribution and the correlation with treatment-related toxicities will be evaluated. Methods: A cone-beam computed tomography (CBCT) based daily dose calculation was performed for a total of 821 CBCT scans of 20 patients with localized PCa treated with IGRT. Each fraction’s dose-volume histogram was analyzed, and toxicities were correlated with OAR dose exposures. Results: Daily dosimetric evaluation showed a significant increase in bladder V65–V70 and rectum V50–V70 compared to planned values (p ≤ 0.003 each). In contrast to bladder D_mean, the rectum D_mean was significantly increased (0.47 vs. 0.55; p < 0.001). For the bladder an exponential dose-volume relationship was demonstrated, while no dose-volume relationship was found for the rectum. On average, patients with increased genitourinary toxicities received significantly increased bladder D_mean (0.44 vs. 0.63, p = 0.014). Conclusions: Conventional dose evaluation via a summation plan rather underestimates daily dosimetric parameters. For adaptive radiotherapy of PCa, volumetric parameters rather than mean doses should be used for daily treatment planning constraints. Because established dose constraints cannot be reduced to a single fraction, reasonable dose constraints should consider daily positional and volumetric changes, rather than relying on a single planning CT.

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.

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 (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.

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.

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.

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. 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. 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. 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. ds-DECT provides a contrasted image for contouring and a non-contrasted image for radiotherapy treatment planning for LTM in motion.

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 H‑VMAT—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 H‑VMAT plans and a 3D-CRT plan as reference. H‑VMAT plans consisted of two treatment plans including 3D-CRT and VMAT. During H‑VMAT 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 H‑VMAT plans showed consistently better PTV dose coverage, conformity, and homogeneity. Additionally, OAR protection was significantly improved with several H‑VMAT combinations (p < 0.05). The comparison of different H‑VMAT 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 H‑VMAT technique is an effective possibility for generating homogenous and conformal dose distributions. With the right choice of H‑VMAT combination, superior OAR protection is achieved compared to 3D-CRT.

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.