Publications by authors named "Stefanie Corradini"

100 Publications

Mammary Chain Irradiation in Left-Sided Breast Cancer: Can We Reduce the Risk of Secondary Cancer and Ischaemic Heart Disease with Modern Intensity-Modulated Radiotherapy Techniques?

Breast Care (Basel) 2021 Aug 19;16(4):358-367. Epub 2020 Oct 19.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Introduction: The aim of the present study was to estimate the impact of the addition of internal mammary chain (IMC) irradiation in node-positive left-sided breast cancer (BC) patients undergoing regional nodal irradiation (RNI) and comparatively evaluate excess relative and absolute risks of radiation-induced lung cancer/BC and ischaemic heart disease for intensity-modulated radiotherapy (IMRT) versus 3D conformal radiotherapy (3D-CRT).

Methods: Four treatment plans were created (3D-CRT and IMRT -/+ IMC) for each of the 10 evaluated patients, and estimates of excess relative risk (ERR) and 10-year excess absolute risk (EAR) were calculated for radiation-induced lung cancer/BC and coronary events using linear, linear-exponential and plateau models.

Results: The addition of IMC irradiation to RNI significantly increased the dose exposure of the heart, lung and contralateral breast using both techniques, increasing ERR for secondary lung cancer (58 vs. 44%, = 0.002), contralateral BC (49 vs. 31%, = 0.002) and ischaemic heart disease (41 vs. 27%, = 0.002, IMRT plans). IMRT significantly reduced the mean cardiac dose and mean lung dose as compared to 3D-CRT, decreasing ERR for major coronary events (64% 3D-CRT vs. 41% IMRT, = 0.002) and ERR for secondary lung cancer (75 vs. 58%, = 0.004) in IMC irradiation, without a significant impact on secondary contralateral BC risks.

Conclusion: Although IMC irradiation has been shown to increase survival rates in node-positive BC patients, it increased dose exposure of organs at risk in left-sided BC, resulting in significantly increased risks for secondary lung cancer/contralateral BC and ischaemic heart disease. In this setting, the adoption of IMRT seems advantageous when compared to 3D-CRT.
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http://dx.doi.org/10.1159/000509779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436658PMC
August 2021

Risk Stratification Using F-FDG PET/CT and Artificial Neural Networks in Head and Neck Cancer Patients Undergoing Radiotherapy.

Diagnostics (Basel) 2021 Aug 31;11(9). Epub 2021 Aug 31.

Department of Radiation Oncology, University Hospital, LMU Munich, 81377 Munich, Germany.

This study retrospectively analyzed the performance of artificial neural networks (ANN) to predict overall survival (OS) or locoregional failure (LRF) in HNSCC patients undergoing radiotherapy, based on 2-[F]FDG PET/CT and clinical covariates. We compared predictions relying on three different sets of features, extracted from 230 patients. Specifically, (i) an automated feature selection method independent of expert rating was compared with (ii) clinical variables with proven influence on OS or LRF and (iii) clinical data plus expert-selected SUV metrics. The three sets were given as input to an artificial neural network for outcome prediction, evaluated by Harrell's concordance index (HCI) and by testing stratification capability. For OS and LRF, the best performance was achieved with expert-based PET-features (0.71 HCI) and clinical variables (0.70 HCI), respectively. For OS stratification, all three feature sets were significant, whereas for LRF only expert-based PET-features successfully classified low vs. high-risk patients. Based on 2-[F]FDG PET/CT features, stratification into risk groups using ANN for OS and LRF is possible. Differences in the results for different feature sets confirm the relevance of feature selection, and the key importance of expert knowledge vs. automated selection.
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http://dx.doi.org/10.3390/diagnostics11091581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468242PMC
August 2021

Patient positioning and immobilization procedures for hybrid MR-Linac systems.

Radiat Oncol 2021 Sep 20;16(1):183. Epub 2021 Sep 20.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Hybrid magnetic resonance (MR)-guided linear accelerators represent a new horizon in the field of radiation oncology. By harnessing the favorable combination of on-board MR-imaging with the possibility to daily recalculate the treatment plan based on real-time anatomy, the accuracy in target and organs-at-risk identification is expected to be improved, with the aim to provide the best tailored treatment. To date, two main MR-linac hybrid machines are available, Elekta Unity and Viewray MRIdian. Of note, compared to conventional linacs, these devices raise practical issues due to the positioning phase for the need to include the coil in the immobilization procedure and in order to perform the best reproducible positioning, also in light of the potentially longer treatment time. Given the relative novelty of this technology, there are few literature data regarding the procedures and the workflows for patient positioning and immobilization for MR-guided daily adaptive radiotherapy. In the present narrative review, we resume the currently available literature and provide an overview of the positioning and setup procedures for all the anatomical districts for hybrid MR-linac systems.
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http://dx.doi.org/10.1186/s13014-021-01910-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454038PMC
September 2021

Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19.

Eur J Med Res 2021 Sep 16;26(1):107. Epub 2021 Sep 16.

Medical Faculty, University of Dusseldorf, Dusseldorf, Germany.

Background: COVID-19, the pandemic disease caused by infection with SARS-CoV-2, may take highly variable clinical courses, ranging from symptom-free and pauci-symptomatic to fatal disease. The goal of the current study was to assess the association of COVID-19 clinical courses controlled by patients' adaptive immune responses without progression to severe disease with patients' Human Leukocyte Antigen (HLA) genetics, AB0 blood group antigens, and the presence or absence of near-loss-of-function delta 32 deletion mutant of the C-C chemokine receptor type 5 (CCR5).

Patient And Methods: An exploratory observational study including 157 adult COVID-19 convalescent patients was performed with a median follow-up of 250 days. The impact of different HLA genotypes, AB0 blood group antigens, and the CCR5 mutant CD195 were investigated for their role in the clinical course of COVID-19. In addition, this study addressed levels of severity and morbidity of COVID-19. The association of the immunogenetic background parameters were further related to patients' humoral antiviral immune response patterns by longitudinal observation.

Results: Univariate HLA analyses identified putatively protective HLA alleles (HLA class II DRB1*01:01 and HLA class I B*35:01, with a trend for DRB1*03:01). They were associated with reduced durations of disease instead decreased (rather than increased) total anti-S IgG levels. They had a higher virus neutralizing capacity compared to non-carriers. Conversely, analyses also identified HLA alleles (HLA class II DQB1*03:02 und HLA class I B*15:01) not associated with such benefit in the patient cohort of this study. Hierarchical testing by Cox regression analyses confirmed the significance of the protective effect of the HLA alleles identified (when assessed in composite) in terms of disease duration, whereas AB0 blood group antigen heterozygosity was found to be significantly associated with disease severity (rather than duration) in our cohort. A suggestive association of a heterozygous CCR5 delta 32 mutation status with prolonged disease duration was implied by univariate analyses but could not be confirmed by hierarchical multivariate testing.

Conclusion: The current study shows that the presence of HLA class II DRB1*01:01 and HLA class I B*35:01 is of even stronger association with reduced disease duration in mild and moderate COVID-19 than age or any other potential risk factor assessed. Prospective studies in larger patient populations also including novel SARS-CoV-2 variants will be required to assess the impact of HLA genetics on the capacity of mounting protective vaccination responses in the future.
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http://dx.doi.org/10.1186/s40001-021-00560-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444184PMC
September 2021

Innovative radiation oncology Together - Precise, Personalized, Human : Vision 2030 for radiotherapy & radiation oncology in Germany.

Strahlenther Onkol 2021 Sep 13. Epub 2021 Sep 13.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Purpose: Scientific and clinical achievements in radiation, medical, and surgical oncology are changing the landscape of interdisciplinary oncology. The German Society for Radiation Oncology (DEGRO) working group of young clinicians and scientists (yDEGRO) and the DEGRO representation of associate and full professors (AKRO) are aware of the essential role of radiation oncology in multidisciplinary treatment approaches. Together, yDEGRO and AKRO endorsed developing a German radiotherapy & radiation oncology vision 2030 to address future challenges in patient care, research, and education. The vision 2030 aims to identify priorities and goals for the next decade in the field of radiation oncology.

Methods: The vision development comprised three phases. During the first phase, areas of interest, objectives, and the process of vision development were defined jointly by the yDEGRO, AKRO, and the DEGRO board. In the second phase, a one-day strategy retreat was held to develop AKRO and yDEGRO representatives' final vision from medicine, biology, and physics. The third phase was dedicated to vision interpretation and program development by yDEGRO representatives.

Results: The strategy retreat's development process resulted in conception of the final vision "Innovative radiation oncology Together - Precise, Personalized, Human." The first term "Innovative radiation oncology" comprises the promotion of preclinical research and clinical trials and highlights the development of a national committee for strategic development in radiation oncology research. The term "together" underpins collaborations within radiation oncology departments as well as with other partners in the clinical and scientific setting. "Precise" mainly covers technological precision in radiotherapy as well as targeted oncologic therapeutics. "Personalized" emphasizes biology-directed individualization of radiation treatment. Finally, "Human" underlines the patient-centered approach and points towards the need for individual longer-term career curricula for clinicians and researchers in the field.

Conclusion: The vision 2030 balances the ambition of physical, technological, and biological innovation as well as a comprehensive, patient-centered, and collaborative approach towards radiotherapy & radiation oncology in Germany.
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http://dx.doi.org/10.1007/s00066-021-01843-9DOI Listing
September 2021

HDR Brachytherapy and SBRT as Bridging Therapy to Liver Transplantation in HCC Patients: A Single-Center Experience.

Front Oncol 2021 26;11:717792. Epub 2021 Aug 26.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Background: In the treatment of patients with HCC awaiting liver transplantation (LT), local ablative treatments (LAT) are available either for downstaging or as bridging treatment. We present our clinical experience with both available radiation-based techniques, brachytherapy (BT), and stereotactic body radiotherapy (SBRT).

Methods: All patients diagnosed with HCC and who were treated with BT or SBRT at our institution between 2011 and 2018 were retrospectively reviewed. The current analysis included all patients who subsequently underwent LT.

Results: A total of 14 patients (male=9; female=5) were evaluated. Seven underwent BT for bridging before LT, and seven were treated with SBRT. BT was performed with a prescribed dose of 1 × 15 Gy, while SBRT was applied with 37 Gy (65%-iso) in three fractions in six patients, and one patient was treated with 54 Gy (100%-iso) in nine fractions. The treatment was generally well tolerated. One case of grade 3 bleeding was reported after BT, and one case of liver failure occurred following SBRT. All patients underwent LT after a median time interval of 152 days (range 47-311) after BT and 202 days (range 44-775) following SBRT. In eight cases, no viable tumor was found in the explanted liver, while four liver specimens showed vital tumor. The median follow-up after SBRT was 41 months and 17 months following BT. Overall, no hepatic HCC recurrence occurred following LT.

Conclusion: Both SBRT and BT are feasible and well tolerated as bridging to LT when applied with caution in patients with impaired liver function. Radiation-based treatments can close the gap for patients not suitable for other locally ablative treatment options.
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http://dx.doi.org/10.3389/fonc.2021.717792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426600PMC
August 2021

Online Magnetic Resonance-Guided Radiotherapy (oMRgRT) for Gynecological Cancers.

Front Oncol 2021 27;11:628131. Epub 2021 Aug 27.

Department of Radiation Oncology, University Medical Center Utrecht, University Utrecht, Utrecht, Netherlands.

Radiation therapy (RT) is increasingly being used in gynecological cancer management. RT delivered with curative or palliative intent can be administered alone or combined with chemotherapy or surgery. Advanced treatment planning and delivery techniques such as intensity-modulated radiation therapy, including volumetric modulated arc therapy, and image-guided adaptive brachytherapy allow for highly conformal radiation dose delivery leading to improved tumor control rates and less treatment toxicity. Quality on-board imaging that provides accurate visualization of target and surrounding organs at risk is a critical feature of these advanced techniques. As soft tissue contrast resolution is superior with magnetic resonance imaging (MRI) compared to other imaging modalities, MRI has been used increasingly to delineate tumor from adjacent soft tissues and organs at risk from initial diagnosis to tumor response evaluation. Gynecological cancers often have poor contrast resolution compared to the surrounding tissues on computed tomography scan, and consequently the benefit of MRI is high. One example is in management of locally advanced cervix cancer where adaptive MRI guidance has been broadly implemented for adaptive brachytherapy. The role of MRI for external beam RT is also steadily increasing. MRI information is being used for treatment planning, predicting, and monitoring position shifts and accounting for tissue deformation and target regression during treatment. The recent clinical introduction of online MRI-guided radiation therapy (oMRgRT) could be the next step in high-precision RT. This technology provides a tool to take full advantage of MRI not only at the time of initial treatment planning but as well as for daily position verification and online plan adaptation. Cervical, endometrial, vaginal, and oligometastatic ovarian cancers are being treated on MRI linear accelerator systems throughout the world. This review summarizes the current state, early experience, ongoing trials, and future directions of oMRgRT in the management of gynecological cancers.
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http://dx.doi.org/10.3389/fonc.2021.628131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429611PMC
August 2021

Multifocal high-grade glioma radiotherapy safety and efficacy.

Radiat Oncol 2021 Aug 28;16(1):165. Epub 2021 Aug 28.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Background: Multifocal manifestation of high-grade glioma is a rare disease with very unfavourable prognosis. The pathogenesis of multifocal glioma and pathophysiological differences to unifocal glioma are not fully understood. The optimal treatment of patients suffering from multifocal high-grade glioma is not defined in the current guidelines, therefore individual case series may be helpful as guidance for clinical decision-making.

Methods: Patients with multifocal high-grade glioma treated with conventionally fractionated radiation therapy (RT) in our institution with or without concomitant chemotherapy between April 2011 and April 2019 were retrospectively analysed. Multifocality was neuroradiologically assessed and defined as at least two independent contrast-enhancing foci in the MRI T1 contrast-enhanced sequence. IDH mutational status and MGMT methylation status were assessed from histopathology records. GTV, PTV as well as the V30Gy, V45Gy and D2% volumes of the brain were analysed. Overall and progression-free survival were calculated from the diagnosis until death and from start of radiation therapy until diagnosis of progression of disease in MRI for all patients.

Results: 20 multifocal glioma cases (18 IDH wild-type glioblastoma cases, one diffuse astrocytic glioma, IDH wild-type case with molecular features of glioblastoma and one anaplastic astrocytoma, IDH wild-type case) were included into the analysis. Resection was performed in two cases and stereotactic biopsy only in 18 cases before the start of radiation therapy. At the start of radiation therapy patients were 61 years old in median (range 42-84 years). Histopathological examination showed IDH wild-type in all cases and MGMT promotor methylation in 11 cases (55%). Prescription schedules were 60 Gy (2 Gy × 30), 59.4 Gy (1.8 Gy × 33), 55 Gy (2.2 Gy × 25) and 50 Gy (2.5 Gy × 20) in 15, three, one and one cases, respectively. Concomitant temozolomide chemotherapy was applied in 16 cases, combined temozolomide/lomustine chemotherapy was applied in one case and concomitant bevacizumab therapy in one case. Median number of GTVs was three. Median volume of the sum of the GTVs was 26 cm. Median volume of the PTV was 425.7 cm and median PTV to brain ratio 32.8 percent. Median D2% of the brain was 61.5 Gy (range 51.2-62.7) and median V30Gy and V45 of the brain were 59.9 percent (range 33-79.7) and 40.7 percent (range 14.9-64.1), respectively. Median survival was eight months (95% KI 3.6-12.4 months) and median progression free survival after initiation of RT five months (95% CI 2.8-7.2 months). Grade 2 toxicities were detected in eight cases and grade 3 toxicities in four cases consisting of increasing edema in three cases and one new-onset seizure. One grade 4 toxicity was detected, which was febrile neutropenia related to concomitant chemotherapy.

Conclusion: Conventionally fractionated RT with concomitant chemotherapy could safely be applied in multifocal high-grade glioma in this case series despite large irradiation treatment fields.
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http://dx.doi.org/10.1186/s13014-021-01886-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400399PMC
August 2021

Informed consent and informed intervention: SARS-CoV-2 vaccinations not just call for disclosure of newly emerging safety data but also for hypothesis generation and testing.

Eur J Med Res 2021 Aug 6;26(1):87. Epub 2021 Aug 6.

Department of Radiation Oncology, Medical Faculty, University Hospital Dusseldorf, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany.

Background: COVID-19 infection is a major threat to patients and health care providers around the world. One solution is the vaccination against SARS-CoV-2.

Methods: We performed a comprehensive query of the latest publications on the prevention of viral infections including the recent vaccination program and its side effects.

Results: The situation is evolving rapidly and there is no reasonable alternative to population-scale vaccination programs as currently enrolled.

Conclusion: Therefore, regulatory authorities should consider supplementing their conventional mandate of post-approval pharmacovigilance, which is based on the collection, assessment, and regulatory response to emerging safety findings.
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http://dx.doi.org/10.1186/s40001-021-00558-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343366PMC
August 2021

Dosimetric comparison of MR-linac-based IMRT and conventional VMAT treatment plans for prostate cancer.

Radiat Oncol 2021 Jul 21;16(1):133. Epub 2021 Jul 21.

Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany.

Background: The aim of this study was to evaluate and compare the performance of intensity modulated radiation therapy (IMRT) plans, planned for low-field strength magnetic resonance (MR) guided linear accelerator (linac) delivery (labelled IMRT MRL plans), and clinical conventional volumetric modulated arc therapy (VMAT) plans, for the treatment of prostate cancer (PCa). Both plans used the original planning target volume (PTV) margins. Additionally, the potential dosimetric benefits of MR-guidance were estimated, by creating IMRT MRL plans using smaller PTV margins.

Materials And Methods: 20 PCa patients previously treated with conventional VMAT were considered. For each patient, two different IMRT MRL plans using the low-field MR-linac treatment planning system were created: one with original (orig.) PTV margins and the other with reduced (red.) PTV margins. Dose indices related to target coverage, as well as dose-volume histogram (DVH) parameters for the target and organs at risk (OAR) were compared. Additionally, the estimated treatment delivery times and the number of monitor units (MU) of each plan were evaluated.

Results: The dose distribution in the high dose region and the target volume DVH parameters (D, D, D and V) were similar for all three types of treatment plans, with deviations below 1% in most cases. Both IMRT MRL plans (orig. and red. PTV margins) showed similar homogeneity indices (HI), however worse values for the conformity index (CI) were also found when compared to VMAT. The IMRT MRL plans showed similar OAR sparing when the orig. PTV margins were used but a significantly better sparing was feasible when red. PTV margins were applied. Higher number of MU and longer predicted treatment delivery times were seen for both IMRT MRL plans.

Conclusions: A comparable plan quality between VMAT and IMRT MRL plans was achieved, when applying the same PTV margin. However, online MR-guided adaptive radiotherapy allows for a reduction of PTV margins. With a red. PTV margin, better sparing of the surrounding tissues can be achieved, while maintaining adequate target coverage. Nonetheless, longer treatment delivery times, characteristic for the IMRT technique, have to be expected.
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http://dx.doi.org/10.1186/s13014-021-01858-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296626PMC
July 2021

Cost-Effectiveness Analysis of Local Treatment in Oligometastatic Disease.

Front Oncol 2021 15;11:667993. Epub 2021 Jun 15.

Department of Radiology, University Hospital, LMU Munich, Munich, Germany.

Background: In certain malignancies, patients with oligometastatic disease benefit from radical ablative or surgical treatment. The SABR-COMET trial demonstrated a survival benefit for oligometastatic patients randomized to local stereotactic ablative radiation (SABR) compared to patients receiving standard care (SC) alone. Our aim was to determine the cost-effectiveness of SABR.

Materials And Methods: A decision model based on partitioned survival simulations estimated costs and quality-adjusted life years (QALY) associated with both strategies in a United States setting from a health care perspective. Analyses were performed over the trial duration of six years as well as a long-term horizon of 16 years. Model input parameters were based on the SABR-COMET trial data as well as best available and most recent data provided in the published literature. An annual discount of 3% for costs was implemented in the analysis. All costs were adjusted to 2019 US Dollars according to the United States Consumer Price Index. SABR costs were reported with an average of $11,700 per treatment. Deterministic and probabilistic sensitivity analyses were performed. Incremental costs, effectiveness, and cost-effectiveness ratios (ICER) were calculated. The willingness-to-pay (WTP) threshold was set to $100,000/QALY.

Results: Based on increased overall and progression-free survival, the SABR group showed 0.78 incremental QALYs over the trial duration and 1.34 incremental QALYs over the long-term analysis. Treatment with SABR led to a marginal increase in costs compared to SC alone (SABR: $304,656; SC: $303,523 for 6 years; ICER $1,446/QALY and SABR: $402,888; SC: $350,708 for long-term analysis; ICER $38,874/QALY). Therapy with SABR remained cost-effective until treatment costs of $88,969 over the trial duration (i.e. 7.6 times the average cost). Sensitivity analysis identified a strong model impact for ongoing annual costs of oligo- and polymetastatic disease states.

Conclusion: Our analysis suggests that local treatment with SABR adds QALYs for patients with certain oligometastatic cancers and represents an intermediate- and long-term cost-effective treatment strategy.
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http://dx.doi.org/10.3389/fonc.2021.667993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239286PMC
June 2021

Comparing Local and Systemic Control between Partial- and Whole-Breast Radiotherapy in Low-Risk Breast Cancer-A Meta-Analysis of Randomized Trials.

Cancers (Basel) 2021 Jun 13;13(12). Epub 2021 Jun 13.

Department of Radiation Oncology, Heinrich Heine University, 40225 Dusseldorf, Germany.

Purpose/objective: The standard treatment for localized low-risk breast cancer is breast-conserving surgery, followed by adjuvant radiotherapy and appropriate systemic therapy. As the majority of local recurrences occur at the site of the primary tumor, numerous trials have investigated partial-breast irradiation (PBI) instead of whole-breast treatment (WBI) using a multitude of irradiation techniques and fractionation regimens. This meta-analysis addresses the impact on disease-specific endpoints, such as local and regional control, as well as disease-free survival of PBI compared to that of WBI in published randomized trials.

Material And Methods: We conducted a systematic literature review and searched for randomized trials comparing WBI and PBI in early-stage breast cancer with publication dates after 2009. The meta-analysis was based on the published event rates and the effect sizes for available oncological endpoints of at least two trials reporting on them. We evaluated in-breast tumor recurrences (IBTR), local recurrences at the primary site and elsewhere in the ipsilateral breast, regional recurrences (RR), distant metastasis-free interval (DMFI), disease-free survival (DFS), contralateral breast cancer (CBC), and second primary cancer (SPC). Furthermore, we aimed to assess the impact of different PBI techniques and subgroups on IBTR. We performed all statistical analyses using the inverse variance heterogeneity model to pool effect sizes.

Results: For the intended meta-analysis, we identified 13 trials (overall 15,561 patients) randomizing between PBI and WBI. IBTR was significantly higher after PBI (OR = 1.66; CI-95%: 1.07-2.58; = 0.024) with an absolute difference of 1.35%. We detected significant heterogeneity in the analysis of the PBI technique with intraoperative radiotherapy resulting in higher local relapse rates (OR = 3.67; CI-95%: 2.28-5.90; < 0.001). Other PBI techniques did not show differences to WBI in IBTR. Both strategies were equally effective at the primary tumor site, but PBI resulted in statistically more IBTRs elsewhere in the ipsilateral breast. IBTRs after WBI were more likely to be located at the primary tumor bed, whereas they appeared equally distributed within the breast after PBI. RR was also more frequent after PBI (OR = 1.75; CI-95%: 1.07-2.88; < 0.001), yet we did not detect any differences in DMFI (OR = 1.08; CI-95%: 0.89-1.30; = 0.475). DFS was significantly longer in patients treated with WBI (OR = 1.14; CI-95%: 1.02-1.27; = 0.003). CBC and SPC were not different in the test groups (OR = 0.81; CI-95%: 0.65-1.01; = 0.067 and OR = 1.09; CI-95%: 0.85-1.40; = 0.481, respectively).

Conclusion: Limiting the target volume to partial-breast radiotherapy appears to be appropriate when selecting patients with a low risk for local and regional recurrences and using a suitable technique.
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http://dx.doi.org/10.3390/cancers13122967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231985PMC
June 2021

Validation of the collapsed cone algorithm for HDR liver brachytherapy against Monte Carlo simulations.

Brachytherapy 2021 Jul-Aug;20(4):936-947. Epub 2021 May 15.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany; Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität München, Garching, Germany. Electronic address:

Purpose: To validate the collapsed cone (CC) algorithm against Monte Carlo (MC) simulations for model-based dose calculations in high-dose-rate (HDR) liver brachytherapy.

Methods And Materials: Doses for liver brachytherapy treatment plans of 10 cases were retrospectively recalculated with a model-based approach using Monte Carlo n-Particle Code (MCNP) 6 (Dm,m-MC) and Oncentra Brachy ACE (Dm,m-ACE). Tissue segmentation consisted of assigning uniform compositions and mass densities to predefined Hounsfield Unit (HU) thresholds. Resulting doses were compared according to dose volume histogram parameters typical for clinical routine. These included the percentage liver volume receiving 5 Gy (V5Gy) or 10 Gy (V10Gy), the maximum dose to one cubic centimeter (D1cc) of organs at risk, the clinical target volume (CTV) fractions receiving 150% (V150), 100% (V100), 95% (V95) and 90% (V90) of the prescribed dose and the absolute doses to 95% (D95) and 90% (D90) of the CTV volumes.

Results: Doses from Oncentra Brachy ACE agreed well with MC simulations. Differences were seen far from the source, in low-density regions and bone structures. Median percentage deviations were 1.1% for the liver V5Gy and 0.4% for the liver V10Gy, with deviations of largest magnitude amounting to 2.2% and 1.0%, respectively. Organs at risk had median deviations ranging from 0.3% to 1.5% for D1cc, with outliers ranging up to 4.6%. CTV volume parameter deviations ranged between -1.5% and 0.5%, dose parameter deviations ranged mostly between -2% and 1%, with two outliers at -4.0% and -3.4% for a small CTV.
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http://dx.doi.org/10.1016/j.brachy.2021.03.018DOI Listing
October 2021

Comparison of liver exposure in CT-guided high-dose rate (HDR) interstitial brachytherapy versus SBRT in hepatocellular carcinoma.

Radiat Oncol 2021 May 6;16(1):86. Epub 2021 May 6.

Department of Radiation Oncology, University Hospital, LMU Munich, 81377, Munich, Germany.

Background: In unresectable hepatocellular carcinoma several local ablative treatments are available. Among others, radiation based treatments such as stereotactic body radiotherapy (SBRT) and high-dose rate interstitial brachytherapy (HDR BT) have shown good local control rates.

Methods: We conducted a dose comparison between actually performed HDR BT versus virtually planned SBRT to evaluate the respective clinically relevant radiation exposure to uninvolved liver tissue. Moreover, dose coverage and conformity indices were assessed.

Results: Overall, 46 treatment sessions (71 lesions, 38 patients) were evaluated. HDR BT was applied in a single fraction with a dose prescription of 1 × 15 Gy. D98 was 17.9 ± 1.3 Gy, D50 was 41.8 ± 8.1 Gy. The SBRT was planned with a prescribed dose of 3 × 12.5 Gy (65%-Isodose), D98 was 50.7 ± 3.1 Gy, D2 was 57.0 ± 2.3 Gy, and D50 was 55.2 ± 2.3 Gy. Regarding liver exposure Vliver10Gy was compared to Vliver15.9Gy, Vliver16.2Gy (EQD2 equivalent doses), and Vliver20Gy (clinically relevant dose), all results showed significant differences (p < .001). In a case by case analysis Vliver10Gy was smaller than Vliver20Gy in 38/46 cases (83%). Dmean of the liver was significantly smaller in BT compared to SBRT (p < .001). GTV volume was correlated to the liver exposure and showed an advantage of HDR BT over SBRT in comparison of clinically relevant doses, and for EQD2 equivalent doses. The advantage was more pronounced for greater liver lesions The Conformity Index (CI) was significantly better for BT, while Healthy Tissue Conformity Index (HTCI) and Conformation Number (CN) showed an advantage for SBRT (p < .001).

Conclusion: HDR BT can be advantageous in respect of sparing of normal liver tissue as compared to SBRT, while providing excellent target conformity.
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http://dx.doi.org/10.1186/s13014-021-01812-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103624PMC
May 2021

MR-Guided Hypofractionated Radiotherapy: Current Emerging Data and Promising Perspectives for Localized Prostate Cancer.

Cancers (Basel) 2021 Apr 9;13(8). Epub 2021 Apr 9.

Advanced Radiation Oncology Department, Sacro Cuore Don Calabria Hospital, 37024 Negrar di Valpolicella, Italy.

In this review we summarize the currently available evidence about the role of hybrid machines for MR-guided radiotherapy for prostate stereotactic body radiotherapy. Given the novelty of this technology, to date few data are accessible, but they all report very promising results in terms of tolerability and preliminary clinical outcomes. Most of the studies highlight the favorable impact of on-board magnetic resonance imaging as a means to improve target and organs at risk identification with a consequent advantage in terms of dosimetric results, which is expected to relate to a more favorable toxicity pattern. Still, the longer treatment time per session may potentially affect the patient's compliance to the treatment, although first quality of life assessment studies have reported substantial tolerability and no major impact on quality of life. Finally, in this review we hypothesize some future scenarios of further investigation, based on the possibility to explore the superior anatomy visualization and the role of daily adapted treatments provided by hybrid MR-Linacs.
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http://dx.doi.org/10.3390/cancers13081791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070332PMC
April 2021

Simultaneous stereotactic radiosurgery of multiple brain metastases using single-isocenter dynamic conformal arc therapy: a prospective monocentric registry trial.

Strahlenther Onkol 2021 07 21;197(7):601-613. Epub 2021 Apr 21.

Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany.

Background: Single-isocenter dynamic conformal arc (SIDCA) therapy is a technically efficient way of delivering stereotactic radiosurgery (SRS) to multiple metastases simultaneously. This study reports on the safety and feasibility of linear accelerator (LINAC) based SRS with SIDCA for patients with multiple brain metastases.

Methods: All patients who received SRS with this technique between November 2017 and June 2019 within a prospective registry trial were included. The patients were irradiated with a dedicated planning tool for multiple brain metastases using a LINAC with a 5 mm multileaf collimator. Follow-up was performed every 3 months, including clinical and radiological examination with cranial magnetic resonance imaging (MRI). These early data were analyzed using descriptive statistics and the Kaplan-Meier method.

Results: A total of 65 patients with 254 lesions (range 2-12) were included in this analysis. Median beam-on time was 23 min. The median follow-up at the time of analysis was 13 months (95% CI 11.1-14.9). Median overall survival and median intracranial progression-free survival was 15 months (95% CI 7.7-22.3) and 7 months (95% CI 3.9-10.0), respectively. Intracranial and local control after 1 year was 64.6 and 97.5%, respectively. During follow-up, CTCAE grade I adverse effects (AE) were experienced by 29 patients (44.6%; 18 of them therapy related, 27.7%), CTCAE grade II AEs by four patients (6.2%; one of them therapy related, 1.5%), and CTCAE grade III by three patients (4.6%; none of them therapy related). Two lesions (0.8%) in two patients (3.1%) were histopathologically proven to be radiation necrosis.

Conclusion: Simultaneous SRS using SIDCA seems to be a feasible and safe treatment for patients with multiple brain metastases.
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http://dx.doi.org/10.1007/s00066-021-01773-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219560PMC
July 2021

MR-Guided Radiotherapy for Liver Malignancies.

Front Oncol 2021 1;11:616027. Epub 2021 Apr 1.

Radiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada.

MR guided radiotherapy represents one of the most promising recent technological innovations in the field. The possibility to better visualize therapy volumes, coupled with the innovative online adaptive radiotherapy and motion management approaches, paves the way to more efficient treatment delivery and may be translated in better clinical outcomes both in terms of response and reduced toxicity. The aim of this review is to present the existing evidence about MRgRT applications for liver malignancies, discussing the potential clinical advantages and the current pitfalls of this new technology.
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http://dx.doi.org/10.3389/fonc.2021.616027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047407PMC
April 2021

Feasibility and Early Clinical Experience of Online Adaptive MR-Guided Radiotherapy of Liver Tumors.

Cancers (Basel) 2021 Mar 26;13(7). Epub 2021 Mar 26.

Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr 15, 81377 Munich, Germany.

Purpose: To assess the feasibility and early results of online adaptive MR-guided radiotherapy (oMRgRT) of liver tumors.

Methods: We retrospectively examined consecutive patients with primary or secondary liver lesions treated at our institution using a 0.35T hybrid MR-Linac (Viewray Inc., Mountain View, CA, USA). Online-adaptive treatment planning was used to account for interfractional anatomical changes, and real-time intrafractional motion management using online 2D cine MRI was performed using a respiratory gating approach. Treatment response and toxicity were assessed during follow-up.

Results: Eleven patients and a total of 15 lesions were evaluated. Histologies included cholangiocarcinomas and metastases of neuroendocrine tumors, colorectal carcinomas, sarcomas and a gastrointestinal stroma tumor. The median BED of the PTV prescription doses was 84.4 Gy (range 59.5-112.5 Gy) applied in 3-5 fractions and the mean GTV BED was in median 147.9 Gy (range 71.7-200.5 Gy). Online plan adaptation was performed in 98% of fractions. The median overall treatment duration was 53 min. The treatment was feasible and successfully completed in all patients. After a median follow-up of five months, no local failure occurred and no ≥ grade two toxicity was observed. OMRgRT resulted in better PTV coverage and fewer OAR constraint violations.

Conclusion: Early results of MR-linac based oMRgRT for the primary and secondary liver tumors are promising. The treatment was feasible in all cases and well tolerated with minimal toxicity. The technique should be compared to conventional SBRT in further studies to assess the advantages of the technique.
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http://dx.doi.org/10.3390/cancers13071523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037065PMC
March 2021

ESTRO-ACROP recommendations on the clinical implementation of hybrid MR-linac systems in radiation oncology.

Radiother Oncol 2021 06 26;159:146-154. Epub 2021 Mar 26.

Department of Radiation Oncology, University Hospital, LMU Munich, Germany.

Online magnetic resonance-guided radiotherapy (oMRgRT) represents one of the most innovative applications of current image-guided radiation therapy (IGRT). The revolutionary concept of oMRgRT systems is the ability to acquire MR images for adaptive treatment planning and also online imaging during treatment delivery. The daily adaptive planning strategies allow to improve targeting accuracy while avoiding critical structures. This ESTRO-ACROP recommendation aims to provide an overview of available systems and guidance for best practice in the implementation phase of hybrid MR-linac systems. Unlike the implementation of other radiotherapy techniques, oMRgRT adds the MR environment to the daily practice of radiotherapy, which might be a new experience for many centers. New issues and challenges that need to be thoroughly explored before starting clinical treatments will be highlighted.
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http://dx.doi.org/10.1016/j.radonc.2021.03.025DOI Listing
June 2021

MR-guided stereotactic body radiation therapy for primary cardiac sarcomas.

Radiat Oncol 2021 Mar 26;16(1):60. Epub 2021 Mar 26.

Department of Bioimaging, Radiation Oncology and Hematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

Background: Primary cardiac tumors are an extremely rare disease with limited prognosis. The treatment of choice is surgery. Other treatment options include chemotherapy and radiation therapy, which historically represented a palliative approach in patients who were not eligible for surgery. The development of hybrid MR-guided radiation therapy makes it possible to better visualize cardiac lesions and to apply high doses per fraction in sensible organs such as the heart.

Case Presentation: Patients affected by inoperable primary cardiac sarcomas and treated at two different institutions were considered for this analysis and retrospectively analyzed. All patients were treated using a 0.35 T hybrid MR Linac system (MRIdian, ViewRay Inc., Mountain View, CA). In the present study we investigated the feasibility, early outcome and toxicity of MR-guided RT in primary cardiac sarcomas. Four consecutive non-metastasized patients who were treated between 05-09/2020 were analyzed. The cardiac sarcomas were mostly located in the right atrium (50%) and one patient presented with 3 epicardial lesions. All patients received MRgRT as a salvage treatment for recurrent cardiac sarcoma after initial surgery, after a mean interval of 12 months (range 1-29 months). Regarding the treatment characteristics, the mean GTV size was 22.9 cc (range 2.5-56.9 cc) and patients were treated with a mean GTV dose of 38.9 Gy (range 30.1-41.1 Gy) in 5 fractions. Regarding feasibility, all treatments were completed as planned and all patients tolerated the treatment very well and showed only mild grade 1 or 2 symptoms like fatigue, dyspnea or mild chest pain at early follow-up.

Conclusion: To the best of our knowledge, in this retrospective analysis we present the first and largest series of patients presenting with primary cardiac sarcomas treated with online adaptive MRgRT. However, further studies are needed to evaluate the impact of this new methodology on the outcome of this very rare disease.
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http://dx.doi.org/10.1186/s13014-021-01791-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995725PMC
March 2021

Distant metastasis time to event analysis with CNNs in independent head and neck cancer cohorts.

Sci Rep 2021 03 19;11(1):6418. Epub 2021 Mar 19.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, 81377, Germany.

Deep learning models based on medical images play an increasingly important role for cancer outcome prediction. The standard approach involves usage of convolutional neural networks (CNNs) to automatically extract relevant features from the patient's image and perform a binary classification of the occurrence of a given clinical endpoint. In this work, a 2D-CNN and a 3D-CNN for the binary classification of distant metastasis (DM) occurrence in head and neck cancer patients were extended to perform time-to-event analysis. The newly built CNNs incorporate censoring information and output DM-free probability curves as a function of time for every patient. In total, 1037 patients were used to build and assess the performance of the time-to-event model. Training and validation was based on 294 patients also used in a previous benchmark classification study while for testing 743 patients from three independent cohorts were used. The best network could reproduce the good results from 3-fold cross validation [Harrell's concordance indices (HCIs) of 0.78, 0.74 and 0.80] in two out of three testing cohorts (HCIs of 0.88, 0.67 and 0.77). Additionally, the capability of the models for patient stratification into high and low-risk groups was investigated, the CNNs being able to significantly stratify all three testing cohorts. Results suggest that image-based deep learning models show good reliability for DM time-to-event analysis and could be used for treatment personalisation.
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http://dx.doi.org/10.1038/s41598-021-85671-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979766PMC
March 2021

Epigenetic modification via H3K4me3 and H3K9ac in human placenta is reduced in preeclampsia.

J Reprod Immunol 2021 06 17;145:103287. Epub 2021 Feb 17.

Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. Electronic address:

Backround: Alterations of DNA accessibility and chromatin structure are associated with diseases. We aimed to investigate epigenetic modifications in preeclampsia (PE), a pregnancy-associated hypertonic disease. Specifically, we addressed histone modification proteins H3K9ac (acetylated lysine 9 of the histone H3) and H3K4me3 (trimethylated lysine 4 of the histone H3) in PE.

Methods: We analyzed expression of histone proteins H3K4me3 and H3K9ac in 32 PE and 32 control placentas by immunohistochemistry. Further, we carried out confirmatory western blot analysis of respective proteins in 6 representative placentas. We then applied regression models with additional adjustment for potential confounders.

Results: Expression of H3K4me3 and H3K9ac is reduced in PE placentas as demonstrated by immunohistochemical stainings and western blot. There are no differences between female and male fetuses in the presence of these histone modifications. H3K4me3 positively correlated with maternal age (r = 0.444, p = 0.034).

Conclusion: Expression of the placental histone proteins H3K4me3 and H3K9ac is reduced in PE, and independent of fetal gender. Our study underlines the involvement of epigenetic changes in the placenta of women suffering from PE.
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http://dx.doi.org/10.1016/j.jri.2021.103287DOI Listing
June 2021

The role of radiotherapy in patients with solid tumours after solid organ transplantation: a systematic review.

Lancet Oncol 2021 03;22(3):e93-e104

Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy; Radiation Oncology, University of Brescia, Brescia, Italy.

For patients diagnosed with cancer who have previously received an organ transplant, radiotherapy represents a challenging clinical scenario without well established care algorithms. Immunosuppressive therapy can be a cause for concern among clinicians treating this category of patients. Potential immune modulation following irradiation could affect recipient organ tolerance and the outcomes of the transplantation itself. The main aim of this systematic review was to define the safety and effectiveness of radiotherapy in patients diagnosed with cancer who have previously received an organ transplant. We searched PubMed and Embase for articles published between Jan 1, 1995, and April 30, 2020 for studies in patients who had undergone radiotherapy for post-transplantation malignancies. The Review is framed by the PICO (population, intervention, control, and outcomes) criteria, and primarily focuses on modern treatment techniques.
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http://dx.doi.org/10.1016/S1470-2045(20)30590-8DOI Listing
March 2021

X-change symposium: status and future of modern radiation oncology-from technology to biology.

Radiat Oncol 2021 Feb 4;16(1):27. Epub 2021 Feb 4.

Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

Future radiation oncology encompasses a broad spectrum of topics ranging from modern clinical trial design to treatment and imaging technology and biology. In more detail, the application of hybrid MRI devices in modern image-guided radiotherapy; the emerging field of radiomics; the role of molecular imaging using positron emission tomography and its integration into clinical routine; radiation biology with its future perspectives, the role of molecular signatures in prognostic modelling; as well as special treatment modalities such as brachytherapy or proton beam therapy are areas of rapid development. More clinically, radiation oncology will certainly find an important role in the management of oligometastasis. The treatment spectrum will also be widened by the rational integration of modern systemic targeted or immune therapies into multimodal treatment strategies. All these developments will require a concise rethinking of clinical trial design. This article reviews the current status and the potential developments in the field of radiation oncology as discussed by a panel of European and international experts sharing their vision during the "X-Change" symposium, held in July 2019 in Munich (Germany).
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http://dx.doi.org/10.1186/s13014-021-01758-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863262PMC
February 2021

Measures of infection prevention and incidence of SARS-CoV-2 infections in cancer patients undergoing radiotherapy in Germany, Austria and Switzerland.

Strahlenther Onkol 2020 12 10;196(12):1068-1079. Epub 2020 Sep 10.

Medical Faculty, Department of Radiation Oncology, Heinrich Heine University, Duesseldorf, Germany.

Purpose: COVID-19 infection has manifested as a major threat to both patients and healthcare providers around the world. Radiation oncology institutions (ROI) deliver a major component of cancer treatment, with protocols that might span over several weeks, with the result of increasing susceptibility to COVID-19 infection and presenting with a more severe clinical course when compared with the general population. The aim of this manuscript is to investigate the impact of ROI protocols and performance on daily practice in the high-risk cancer patients during this pandemic.

Methods: We addressed the incidence of positive COVID-19 cases in both patients and health care workers (HCW), in addition to the protective measures adopted in ROIs in Germany, Austria and Switzerland using a specific questionnaire.

Results: The results of the questionnaire showed that a noteworthy number of ROIs were able to complete treatment in SARS-CoV‑2 positive cancer patients, with only a short interruption. The ROIs reported a significant decrease in patient volume that was not impacted by the circumambient disease incidence, the type of ROI or the occurrence of positive cases. Of the ROIs 16.5% also reported infected HCWs. About half of the ROIs (50.5%) adopted a screening program for patients whereas only 23.3% also screened their HCWs. The range of protective measures included the creation of working groups, instituting home office work and protection with face masks. Regarding the therapeutic options offered, curative procedures were performed with either unchanged or moderately decreased schedules, whereas palliative or benign radiotherapy procedures were more often shortened. Most ROIs postponed or cancelled radiation treatment for benign indications (88.1%). The occurrence of SARS-CoV‑2 infections did not affect the treatment options for curative procedures. Non-university-based ROIs seemed to be more willing to change their treatment options for curative and palliative cases than university-based ROIs.

Conclusion: Most ROIs reported a deep impact of SARS-CoV‑2 infections on their work routine. Modification and prioritization of treatment regimens and the application of protective measures preserved a well-functioning radiation oncology service and patient care.
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http://dx.doi.org/10.1007/s00066-020-01681-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483062PMC
December 2020

Radiotherapy in oncological emergencies: fast-track treatment planning.

Radiat Oncol 2020 Sep 10;15(1):215. Epub 2020 Sep 10.

Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

Background And Purpose: To report on our clinical experience with a newly implemented workflow for radiotherapy (RT) emergency treatments, which allows for a fast treatment application outside the regular working-hours, and its clinical applicability.

Methods: Treatment planning of 18 emergency RT patients was carried out using diagnostic computed tomography (CT) without a dedicated RT simulation CT. The cone-beam CT (CBCT) deviations of the first RT treatment were analyzed regarding setup accuracy. Furthermore, feasibility of the "fast-track" workflow was evaluated with respect to dose deviations caused by different Hounsfield unit (HU) to relative electron density (rED) calibrations and RT treatment couch surface shapes via 3D gamma index analysis of exemplary treatment plans. The dosimetric uncertainty introduced by different CT calibrations was quantified.

Results: Mean patient setup vs. CBCT isocenter deviations were (0.49 ± 0.44) cm (x), (2.68 ± 1.63) cm (y) and (1.80 ± 1.06) cm (z) for lateral, longitudinal and vertical directions, respectively. Three out of four dose comparisons between the emergency RT plan calculated on the diagnostic CT and the same plan calculated on the treatment planning CT showed clinically acceptable gamma passing rates, when correcting for surface artifacts. The maximum difference of rED was 0.054, while most parts of the CT calibration curves coincided well.

Conclusion: In an emergency RT setting, the use of diagnostic CT data for treatment planning might be time-saving and was shown to be suitable for many cases, considering reproducibility of patient setup, accuracy of initial patient setup and accuracy of dose-calculation.
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http://dx.doi.org/10.1186/s13014-020-01657-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488151PMC
September 2020

Prostate re-irradiation: current concerns and future perspectives.

Expert Rev Anticancer Ther 2020 11 29;20(11):947-956. Epub 2020 Sep 29.

Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Negrar , Verona, Italy.

Introduction: To date, the optimal management of locally relapsed prostate cancer patients after an initial course of radiotherapy remains a matter of debate. In recent years, local approaches have been proposed as a therapeutic option, which may potentially delay the initiation of hormone therapy. In the case of external beam radiotherapy (EBRT), re-irradiation has been supported by growing evidence in the literature, mostly represented by extreme hypofractionated schedules delivered with stereotactic body radiotherapy (SBRT).

Areas Covered: We performed a systematic review of the literature using the PICO methodology to explore the available evidence regarding the use of EBRT in the setting of locally relapsed prostate cancer, both in terms of safety, tolerability and preliminary clinical outcomes.

Expert Opinion: Current literature data report the use of EBRT and particularly of SBRT for the safe and feasible re-treatment of locally recurrent prostate cancer after an initial treatment course of radiotherapy. When extreme hypofractionation is adopted, only occasional grade ≥3 late adverse events are reported. Despite the current lack of high-level evidence and the short follow-up, preliminary clinical outcomes are promising and allow clinicians to hypothesize further prospective studies to evaluate SBRT as an alternative to the early initiation of androgen-deprivation therapy.
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http://dx.doi.org/10.1080/14737140.2020.1822742DOI Listing
November 2020

No Difference in Overall Survival and Non-Breast Cancer Deaths after Partial Breast Radiotherapy Compared to Whole Breast Radiotherapy-A Meta-Analysis of Randomized Trials.

Cancers (Basel) 2020 Aug 17;12(8). Epub 2020 Aug 17.

Department of Radiation Oncology, Heinrich Heine University, 40225 Duesseldorf, Germany.

Purpose/objective: Adjuvant radiotherapy after breast conserving surgery is the standard approach in early stage breast cancer. However, the extent of breast tissue that has to be targeted with radiation has not been determined yet. Traditionally, the whole breast was covered by two opposing tangential beams. Several randomized trials have tested partial breast irradiation (PBI) compared to whole breast irradiation (WBI) using different radiation techniques. There is evidence from randomized trials that PBI might result in lower mortality rates compared to WBI. We aimed to reassess this question using current data from randomized trials.

Material/methods: We performed a systematic literature review searching for randomized trials comparing WBI and PBI in early stage breast cancer with publication dates after 2009. The meta-analysis was performed using the published event rates and the effect sizes for overall survival (OS), breast cancer-specific survival (BCSS), and non-breast cancer death (NBCD) as investigated endpoints. Analysis of subgroups using different radiation techniques was intended. We used hazard ratios (HR) and risk differences (RD) to estimate pooled effect sizes. Statistical analysis was performed using the inverse variance heterogeneity model.

Results: We identified eleven studies randomizing between PBI and WBI. We did not find significant differences in OS ( = 14,070; HR = 1.02; CI-95%: 0.89-1.16; = 0.810, and = 15,203; RD = -0.001; CI-95%: -0.008-0.006; = 0.785) and BCSS ( = 15,203; RD = 0.001; CI-95%: -0.002-0.005; = 0.463). PBI also did not result in a significant decrease of NBCD ( = 15,203; RD = -0.003; CI-95%: -0.010-0.003; = 0.349). A subgroup analysis by radiation technique also did not point to any detectable differences.

Conclusion: In contrast to a previous assessment of mortality, we could not find a detrimental effect of WBI on OS or NBCD. A longer follow-up might be necessary to fully assess the long-term mortality effects of PBI compared to WBI.
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http://dx.doi.org/10.3390/cancers12082309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464494PMC
August 2020
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