Publications by authors named "Maximilian Niyazi"

135 Publications

Interstitial Photodynamic Therapy Using 5-ALA for Malignant Glioma Recurrences.

Cancers (Basel) 2021 Apr 7;13(8). Epub 2021 Apr 7.

Department of Neurosurgery, University Hospital, LMU Munich, 81377 Munich, Germany.

Interstitial photodynamic therapy (iPDT) using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) as a cytotoxic photosensitizer could be a feasible treatment option for malignant gliomas. In a monocentric cohort of consecutive patients treated between 2006 and 2018, a risk profile analysis of salvage iPDT for local malignant glioma recurrences and associated outcome measures are presented here. It was considered indicated in patients with circumscribed biopsy-proven malignant glioma recurrences after standard therapy, if not deemed eligible for safe complete resection. A 3D treatment-planning software was used to determine the number and suitable positions of the cylindrical diffusing fibers placed stereotactically to ensure optimal interstitial irradiation of the target volume. Outcome measurements included the risk profile of the procedure, estimated time-to-treatment-failure (TTF), post-recurrence survival (PRS) and prognostic factors. Forty-seven patients were treated, of which 44 (median age, 49.4 years, range, 33.4-87.0 years, 27 males) could be retrospectively evaluated. Recurrent gliomas included 37 glioblastomas (WHO grade IV) and 7 anaplastic astrocytomas (WHO grade III). Thirty (68.2%) tumors were O-6-methylguanine-DNA methyltransferase (MGMT)-methylated, 29 (65.9%)-isocitrate dehydrogenase (IDH)-wildtype. Twenty-six (59.1%) patients were treated for their first, 9 (20.5%)-for their second, 9 (20.5%)-for the third or further recurrence. The median iPDT target volume was 3.34 cm (range, 0.50-22.8 cm). Severe neurologic deterioration lasted for more than six weeks in one patient only. The median TTF was 7.1 (95% confidence interval (CI), 4.4-9.8) months and the median PRS was 13.0 (95% CI, 9.2-16.8) months. The 2- and 5-year PRS rates were 25.0% and 4.5%, respectively. The treatment response was heterogeneous and not significantly associated with patient characteristics, treatment-related factors or molecular markers. The promising outcome and acceptable risk profile deserve further prospective evaluation particularly to identify mechanisms and prognostic factors of favorable treatment response.
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http://dx.doi.org/10.3390/cancers13081767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067827PMC
April 2021

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

Strahlenther Onkol 2021 Apr 21. 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
April 2021

Current status and recent advances in resection cavity irradiation of brain metastases.

Radiat Oncol 2021 Apr 15;16(1):73. Epub 2021 Apr 15.

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

Despite complete surgical resection brain metastases are at significant risk of local recurrence without additional radiation therapy. Traditionally, the addition of postoperative whole brain radiotherapy (WBRT) has been considered the standard of care on the basis of randomized studies demonstrating its efficacy in reducing the risk of recurrence in the surgical bed as well as the incidence of new distant metastases. More recently, postoperative stereotactic radiosurgery (SRS) to the surgical bed has emerged as an effective and safe treatment option for resected brain metastases. Published randomized trials have demonstrated that postoperative SRS to the resection cavity provides superior local control compared to surgery alone, and significantly decreases the risk of neurocognitive decline compared to WBRT, without detrimental effects on survival. While studies support the use of postoperative SRS to the resection cavity as the standard of care after surgery, there are several issues that need to be investigated further with the aim of improving local control and reducing the risk of leptomeningeal disease and radiation necrosis, including the optimal dose prescription/fractionation, the timing of postoperative SRS treatment, and surgical cavity target delineation. We provide a clinical overview on current status and recent advances in resection cavity irradiation of brain metastases, focusing on relevant strategies that can improve local control and minimize the risk of radiation-induced toxicity.
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http://dx.doi.org/10.1186/s13014-021-01802-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051036PMC
April 2021

Inhibition of HSP90 as a Strategy to Radiosensitize Glioblastoma: Targeting the DNA Damage Response and Beyond.

Front Oncol 2021 17;11:612354. Epub 2021 Mar 17.

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

Radiotherapy is an essential component of multi-modality treatment of glioblastoma (GBM). However, treatment failure and recurrence are frequent and give rise to the dismal prognosis of this aggressive type of primary brain tumor. A high level of inherent treatment resistance is considered to be the major underlying reason, stemming from constantly activated DNA damage response (DDR) mechanisms as a consequence of oncogene overexpression, persistent replicative stress, and other so far unknown reasons. The molecular chaperone heat shock protein 90 (HSP90) plays an important role in the establishment and maintenance of treatment resistance, since it crucially assists the folding and stabilization of various DDR regulators. Accordingly, inhibition of HSP90 represents a multi-target strategy to interfere with DDR function and to sensitize cancer cells to radiotherapy. Using NW457, a pochoxime-based HSP90 inhibitor with favorable brain pharmacokinetic profile, we show here that HSP90 inhibition at low concentrations with limited cytotoxicity leads to downregulation of various DNA damage response factors on the protein level, distinct transcriptomic alterations, impaired DNA damage repair, and reduced clonogenic survival in response to ionizing irradiation in glioblastoma cells . , HSP90 inhibition by NW457 improved the therapeutic outcome of fractionated CBCT-based irradiation in an orthotopic, syngeneic GBM mouse model, both in terms of tumor progression and survival. Nevertheless, in view of the promising results the efficacy was not as strong as expected, although apart from the radiosensitizing effects HSP90 inhibition also reduced irradiation-induced GBM cell migration and tumor invasiveness. Hence, our findings identify the combination of HSP90 inhibition and radiotherapy in principle as a promising strategy for GBM treatment whose performance needs to be further optimized by improved inhibitor substances, better formulations and/or administration routes, and fine-tuned treatment sequences.
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http://dx.doi.org/10.3389/fonc.2021.612354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011354PMC
March 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

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

Toward Personalized Radiation Therapy of Liver Metastasis: Importance of Serial Blood Biomarkers.

JCO Clin Cancer Inform 2021 Mar;5:315-325

Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

Purpose: To assess the added value of serial blood biomarkers in liver metastasis stereotactic body radiation therapy (SBRT).

Materials And Methods: Eighty-nine patients were retrospectively included. Pre- and midtreatment blood samples were analyzed for potential biomarkers of the treatment response. Three biomarker classes were studied: gene mutation status, complete blood count, and inflammatory cytokine concentration in plasma. One-year local failure (LF) and 2-year overall survival (OS) were chosen as study end points. Multivariate logistic regression was used for response prediction. Added predictive benefit was assessed by quantifying the difference between the predictive performance of a baseline model (clinicopathologic and dosimetric predictors) and that of the biomarker-enhanced model, using three metrics: (1) likelihood ratio, (2) predictive variance, and (3) area under the receiver operating characteristic curve (AUC).

Results: The most important predictors of LF were mutation in gene (hazard ratio [HR] = 2.92, 95% CI, [1.17 to 7.28], = .02) and baseline and midtreatment concentration of plasma interleukin-6 (HR = 1.15 [1.04 to 1.26] and 1.06 [1.01 to 1.13], = .01). Absolute lymphocyte count and platelet-to-lymphocyte ratio at baseline as well as neutrophil-to-lymphocyte ratio at baseline and before fraction 3 (HR = 1.33 [1.16 to 1.51] and 1.19 [1.09 to 1.30]) had the most significant association with OS ( = .0003). Addition of baseline GEN and inflammatory plasma cytokine biomarkers in predicting LF, respectively, increased AUC by 0.06 (from 0.73 to 0.79) and 0.07 (from 0.77 to 0.84). In predicting OS, inclusion of midtreatment complete blood count biomarkers increased AUC from 0.72 to 0.80, along with significant boosts in likelihood ratio and predictive variance.

Conclusion: Inclusion of serial blood biomarkers leads to significant gain in predicting response to liver metastasis stereotactic body radiation therapy and can guide treatment personalization.
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http://dx.doi.org/10.1200/CCI.20.00118DOI Listing
March 2021

Current status and developments of German curriculum-based residency training programmes in radiation oncology.

Radiat Oncol 2021 Mar 20;16(1):55. Epub 2021 Mar 20.

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

Purpose: The current status of German residency training in the field of radiation oncology is provided and compared to programmes in other countries. In particular, we present the DEGRO-Academy within the international context.

Methods: Certified courses from 2018 and 2019 were systematically assigned to the DEGRO-Curriculum, retrospectively for 2018 and prospectively for 2019. In addition, questionnaires of course evaluations were provided, answered by course participants and collected centrally.

Results: Our data reveal a clear increase in curriculum coverage by certified courses from 57.6% in 2018 to 77.5% in 2019. The analyses enable potential improvements in German curriculum-based education. Specific topics of the DEGRO-Curriculum are still underrepresented, while others decreased in representation between 2018 and 2019. It was found that several topics in the DEGRO-Curriculum require more attention because of a low DEGRO-curriculum coverage. Evaluation results of certified courses improved significantly with a median grade of 1.62 in 2018 to 1.47 in 2019 (p = 0.0319).

Conclusion: The increase of curriculum coverage and the simultaneous improvement of course evaluations are promising with respect to educational standards in Germany. Additionally, the early integration of radiation oncology into medical education is a prerequisite for resident training because of rising demands on quality control and increasing patient numbers. This intensified focus is a requirement for continued high standards and quality of curriculum-based education in radiation oncology both in Germany and other countries.
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http://dx.doi.org/10.1186/s13014-021-01785-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981823PMC
March 2021

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

Sci Rep 2021 Mar 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

The number of methylated CpG sites within the MGMT promoter region linearly correlates with outcome in glioblastoma receiving alkylating agents.

Acta Neuropathol Commun 2021 03 4;9(1):35. Epub 2021 Mar 4.

Department of Neurosurgery, University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany.

MGMT-promoter methylation is associated with favorable outcome in glioblastoma. The aim of this study was to determine whether the absolute number of methylated Cytosine-Guanine-dinucleotide-(CpG-)sites within the DMR-2 island of the MGMT-promoter may correlate with outcome in a qualitative or quantitative fashion. In a cohort of newly diagnosed glioblastoma patients treated with stereotactic biopsy or open tumor resection plus concomitant chemoradiotherapy, we assessed MGMT-promoter methylation by methylation-specific polymerase-chain-reaction (MSP). Methylation of the CpG-sites 74-98 within the MGMT-promoter region was additionally analysed by Sanger sequencing, and the total number of methylated CpG-sites was correlated with outcome using proportional hazards models. 215 patients with glioblastoma were identified and stratified per MSP (positive: 53%, negative: 47%). Among MSP-positive tumors, hierarchical clustering identified three subgroups with different methylation rates (median: 80% vs. 52% vs. 47%), indicating a site-dependent methylation propagation. The methylation status of a given CpG-site indicated a neighborhood-dependent methylation propagation. Survival was linearly associated with the cumulative number of methylated CpG-sites. This was particularly true in patients who received at least one adjuvant cycle of temozolomide. Notably, all CpG-sites analyzed contributed similarly to effect size; this enabled a further predictive substratification of MSP-positive tumors with median OS ranging from as low as 17.1 months (< 18 methylated CpG-sites) to as high as 26.2 months (≥ 18 methylated CpG-sites) in the overall cohort. All in all, total number of methylated CpG-sites may correlate with outcome in a linear fashion. Such analysis may therefore add further predictive value to conventional methods of determining the MGMT-promoter status.
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http://dx.doi.org/10.1186/s40478-021-01134-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934240PMC
March 2021

FET-PET radiomics in recurrent glioblastoma: prognostic value for outcome after re-irradiation?

Radiat Oncol 2021 Mar 3;16(1):46. Epub 2021 Mar 3.

German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg, Heidelberg, Germany.

Purpose: The value of O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-positron emission tomography (PET)-radiomics in the outcome assessment of patients with recurrent glioblastoma (rGBM) has not been evaluated until now. The aim of this study was to evaluate whether a prognostic model based on FET-PET radiomics features (RF) is feasible and can identify rGBM patients that would most benefit from re-irradiation.

Methods: We prospectively recruited rGBM patients who underwent FET-PET before re-irradiation (GLIAA-Pilot trial, DRKS00000633). Tumor volume was delineated using a semi-automatic method with a threshold of 1.8 times the standardized-uptake-value of the background. 135 FET-RF (histogram parameters, shape and texture features) were extracted. The analysis involved the characterization of tumor and non-tumor tissue with FET-RF and the evaluation of the prognostic value of FET-RF for time-to-progression (TTP), overall survival (OS) and recurrence location (RL).

Results: Thirty-two rGBM patients constituted our cohort. FET-RF discriminated significantly between tumor and non-tumor. The texture feature Small-Zone-Low-Gray-Level-Emphasis (SZLGE) showed the best performance for the prediction of TTP (p = 0.001, satisfying Bonferroni-multiple-test significance level). Additionally, two radiomics signatures could predict TTP (TTP-radiomics-signature, p = 0.001) and OS (OS-radiomics-signature, p = 0.038). SZLGE and the TTP-radiomics-signature additionally predicted RL. Specifically, high values for TTP-radiomics-signature and for SZLGE indicated not only earlier progression, but also a RL within the initial FET-PET active volume.

Conclusion: Our findings suggest that FET-PET radiomics could contribute to the prognostic assessment and selection of rGBM-patients benefiting from re-irradiation. Trial registration DRKS00000633. Registered on 8th of December in 2010. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00000633 .
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http://dx.doi.org/10.1186/s13014-020-01744-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931514PMC
March 2021

Radiation-induced kidney toxicity: molecular and cellular pathogenesis.

Radiat Oncol 2021 Feb 25;16(1):43. Epub 2021 Feb 25.

Division of Pediatric Nephrology, Department of Pediatrics, Dr. v. Hauner Children's Hospital, University Hospital, LMU Munich, Lindwurmstr. 4, 80337, Munich, Germany.

Radiation nephropathy (RN) is a kidney injury induced by ionizing radiation. In a clinical setting, ionizing radiation is used in radiotherapy (RT). The use and the intensity of radiation therapy is limited by normal-tissue damage including kidney toxicity. Different thresholds for kidney toxicity exist for different entities of RT. Histopathologic features of RN include vascular, glomerular and tubulointerstitial damage. The different molecular and cellular pathomechanisms involved in RN are not fully understood. Ionizing radiation causes double-stranded breaks in the DNA, followed by cell death including apoptosis and necrosis of renal endothelial, tubular and glomerular cells. Especially in the latent phase of RN oxidative stress and inflammation have been proposed as putative pathomechanisms, but so far no clear evidence was found. Cellular senescence, activation of the renin-angiotensin-aldosterone-system and vascular dysfunction might contribute to RN, but only limited data is available. Several signalling pathways have been identified in animal models of RN and different approaches to mitigate RN have been investigated. Drugs that attenuate cell death and inflammation or reduce oxidative stress and renal fibrosis were tested. Renin-angiotensin-aldosterone-system blockade, anti-apoptotic drugs, statins, and antioxidants have been shown to reduce the severity of RN. These results provide a rationale for the development of new strategies to prevent or reduce radiation-induced kidney toxicity.
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http://dx.doi.org/10.1186/s13014-021-01764-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905925PMC
February 2021

Radiation necrosis after a combination of external beam radiotherapy and iodine-125 brachytherapy in gliomas.

Radiat Oncol 2021 Feb 23;16(1):40. Epub 2021 Feb 23.

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

Purpose: Frequency and risk profile of radiation necrosis (RN) in patients with glioma undergoing either upfront stereotactic brachytherapy (SBT) and additional salvage external beam radiotherapy (EBRT) after tumor recurrence or vice versa remains unknown.

Methods: Patients with glioma treated with low-activity temporary iodine-125 SBT at the University of Munich between 1999 and 2016 who had either additional upfront or salvage EBRT were included. Biologically effective doses (BED) were calculated. RN was diagnosed using stereotactic biopsy and/or metabolic imaging. The rate of RN was estimated with the Kaplan Meier method. Risk factors were obtained from logistic regression models.

Results: Eighty-six patients (49 male, 37 female, median age 47 years) were included. 38 patients suffered from low-grade and 48 from high-grade glioma. Median follow-up was 15 months after second treatment. Fifty-eight patients received upfront EBRT (median total dose: 60 Gy), and 28 upfront SBT (median reference dose: 54 Gy, median dose rate: 10.0 cGy/h). Median time interval between treatments was 19 months. RN was diagnosed in 8/75 patients. The 1- and 2-year risk of RN was 5.1% and 11.7%, respectively. Tumor volume and irradiation time of SBT, number of implanted seeds, and salvage EBRT were risk factors for RN. Neither of the BED values nor the time interval between both treatments gained prognostic influence.

Conclusion: The combination of upfront EBRT and salvage SBT or vice versa is feasible for glioma patients. The risk of RN is mainly determined by the treatment volume but not by the interval between therapies.
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http://dx.doi.org/10.1186/s13014-021-01762-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903688PMC
February 2021

Current status and recent advances in reirradiation of glioblastoma.

Radiat Oncol 2021 Feb 18;16(1):36. Epub 2021 Feb 18.

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

Despite aggressive management consisting of maximal safe surgical resection followed by external beam radiation therapy (60 Gy/30 fractions) with concomitant and adjuvant temozolomide, approximately 90% of WHO grade IV gliomas (glioblastomas, GBM) will recur locally within 2 years. For patients with recurrent GBM, no standard of care exists. Thanks to the continuous improvement in radiation science and technology, reirradiation has emerged as feasible approach for patients with brain tumors. Using stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT), either hypofractionated or conventionally fractionated schedules, several studies have suggested survival benefits following reirradiation of patients with recurrent GBM; however, there are still questions to be answered about the efficacy and toxicity associated with a second course of radiation. We provide a clinical overview on current status and recent advances in reirradiation of GBM, addressing relevant clinical questions such as the appropriate patient selection and radiation technique, optimal dose fractionation, reirradiation tolerance of the brain and the risk of radiation necrosis.
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http://dx.doi.org/10.1186/s13014-021-01767-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890828PMC
February 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

Contribution of PET imaging to radiotherapy planning and monitoring in glioma patients - a report of the PET/RANO group.

Neuro Oncol 2021 Feb 4. Epub 2021 Feb 4.

German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.

The management of patients with glioma usually requires multimodality treatment including surgery, radiotherapy, and systemic therapy. Accurate neuroimaging plays a central role for radiotherapy planning and follow-up after radiotherapy completion. In order to maximize the radiation dose to the tumor and to minimize toxic effects on the surrounding brain parenchyma, reliable identification of tumor extent and target volume delineation is crucial. The use of PET for radiotherapy planning and monitoring in gliomas has gained considerable interest over the last several years, but Class I data are not yet available. Furthermore, PET has been used after radiotherapy for response assessment and to distinguish tumor progression from pseudoprogression or radiation necrosis. Here, the RANO working group provides a summary of the literature and recommendations for the use of PET imaging for radiotherapy of patients with glioma based on published studies, constituting levels 1-3 evidence according to the Oxford Centre for Evidence-based Medicine.
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http://dx.doi.org/10.1093/neuonc/noab013DOI Listing
February 2021

A Privacy-Preserving Log-Rank Test for the Kaplan-Meier Estimator With Secure Multiparty Computation: Algorithm Development and Validation.

JMIR Med Inform 2021 Jan 18;9(1):e22158. Epub 2021 Jan 18.

Chair of Network Architectures and Services, Department of Informatics, Technical University of Munich, TUM, Garching, Germany.

Background: Patient data is considered particularly sensitive personal data. Privacy regulations strictly govern the use of patient data and restrict their exchange. However, medical research can benefit from multicentric studies in which patient data from different institutions are pooled and evaluated together. Thus, the goals of data utilization and data protection are in conflict. Secure multiparty computation (SMPC) solves this conflict because it allows direct computation on distributed proprietary data-held by different data owners-in a secure way without exchanging private data.

Objective: The objective of this work was to provide a proof-of-principle of secure and privacy-preserving multicentric computation by SMPC with real-patient data over the free internet. A privacy-preserving log-rank test for the Kaplan-Meier estimator was implemented and tested in both an experimental setting and a real-world setting between two university hospitals.

Methods: The domain of survival analysis is particularly relevant in clinical research. For the Kaplan-Meier estimator, we provided a secure version of the log-rank test. It was based on the SMPC realization SPDZ and implemented via the FRESCO framework in Java. The complexity of the algorithm was explored both for synthetic data and for real-patient data in a proof-of-principle over the internet between two clinical institutions located in Munich and Berlin, Germany.

Results: We obtained a functional realization of an SMPC-based log-rank evaluation. This implementation was assessed with respect to performance and scaling behavior. We showed that network latency strongly influences execution time of our solution. Furthermore, we identified a lower bound of 2 Mbit/s for the transmission rate that has to be fulfilled for unimpeded communication. In contrast, performance of the participating parties have comparatively low influence on execution speed, since the peer-side processing is parallelized and the computational time only constitutes 30% to 50% even with optimal network settings. In the real-world setting, our computation between three parties over the internet, processing 100 items each, took approximately 20 minutes.

Conclusions: We showed that SMPC is applicable in the medical domain. A secure version of commonly used evaluation methods for clinical studies is possible with current implementations of SMPC. Furthermore, we infer that its application is practically feasible in terms of execution time.
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http://dx.doi.org/10.2196/22158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850908PMC
January 2021

Peer review analysis in the field of radiation oncology: results from a web-based survey of the Young DEGRO working group.

Strahlenther Onkol 2020 Dec 18. Epub 2020 Dec 18.

Department of Radiation Oncology, University Hospital Jena, Jena, Germany.

Purpose: To evaluate the reviewing behaviour in the German-speaking countries in order to provide recommendations to increase the attractiveness of reviewing activity in the field of radiation oncology.

Methods: In November 2019, a survey was conducted by the Young DEGRO working group (jDEGRO) using the online platform "eSurveyCreator". The questionnaire consisted of 29 items examining a broad range of factors that influence reviewing motivation and performance.

Results: A total of 281 responses were received. Of these, 154 (55%) were completed and included in the evaluation. The most important factors for journal selection criteria and peer review performance in the field of radiation oncology are the scientific background of the manuscript (85%), reputation of the journal (59%) and a high impact factor (IF; 40%). Reasons for declining an invitation to review include the scientific background of the article (60%), assumed effort (55%) and a low IF (27%). A double-blind review process is preferred by 70% of respondents to a single-blind (16%) or an open review process (14%). If compensation was offered, 59% of participants would review articles more often. Only 12% of the participants have received compensation for their reviewing activities so far. As compensation for the effort of reviewing, 55% of the respondents would prefer free access to the journal's articles, 45% a discount for their own manuscripts, 40% reduced congress fees and 39% compensation for expenses.

Conclusion: The scientific content of the manuscript, reputation of the journal and a high IF determine the attractiveness for peer reviewing in the field of radiation oncology. The majority of participants prefer a double-blind peer review process and would conduct more reviews if compensation was available. Free access to journal articles, discounts for publication costs or congress fees, or an expense allowance were identified to increase attractiveness of the review process.
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http://dx.doi.org/10.1007/s00066-020-01729-2DOI Listing
December 2020

ESTRO ACROP guideline for target volume delineation of skull base tumors.

Radiother Oncol 2021 03 10;156:80-94. Epub 2020 Dec 10.

Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy; IRCCS Neuromed, Pozzilli, Italy. Electronic address:

Background And Purpose: For skull base tumors, target definition is the key to safe high-dose treatments because surrounding normal tissues are very sensitive to radiation. In the present work we established a joint ESTRO ACROP guideline for the target volume definition of skull base tumors.

Material And Methods: A comprehensive literature search was conducted in PubMed using various combinations of the following medical subjects headings (MeSH) and free-text words: "radiation therapy" or "stereotactic radiosurgery" or "proton therapy" or "particle beam therapy" and "skull base neoplasms" "pituitary neoplasms", "meningioma", "craniopharyngioma", "chordoma", "chondrosarcoma", "acoustic neuroma/vestibular schwannoma", "organs at risk", "gross tumor volume", "clinical tumor volume", "planning tumor volume", "target volume", "target delineation", "dose constraints". The ACROP committee identified sixteen European experts in close interaction with the ESTRO clinical committee who analyzed and discussed the body of evidence concerning target delineation.

Results: All experts agree that magnetic resonance (MR) images with high three-dimensional spatial accuracy and tissue-contrast definition, both T2-weighted and volumetric T1-weighted sequences, are required to improve target delineation. In detail, several key issues were identified and discussed: i) radiation techniques and immobilization, ii) imaging techniques and target delineation, and iii) technical aspects of radiation treatments including planning techniques and dose-fractionation schedules. Specific target delineation issues with regard to different skull base tumors, including pituitary adenomas, meningiomas, craniopharyngiomas, acoustic neuromas, chordomas and chondrosarcomas are presented.

Conclusions: This ESTRO ACROP guideline achieved detailed recommendations on target volume definition for skull base tumors, as well as comprehensive advice about imaging modalities and radiation techniques.
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http://dx.doi.org/10.1016/j.radonc.2020.11.014DOI Listing
March 2021

Improved risk stratification in younger wild-type glioblastoma patients by combining a 4-miRNA signature with promoter methylation status.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa137. Epub 2020 Oct 15.

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

Background: The potential benefit of risk stratification using a 4-miRNA signature in combination with promoter methylation in wild-type glioblastoma patients was assessed.

Methods: Primary tumors from 102 patients with comparable treatment from the LMU Munich ( = 37), the University Hospital Düsseldorf ( = 33), and The Cancer Genome Atlas ( = 32) were included. Risk groups were built using expressions of hsa-let-7a-5p, hsa-let-7b-5p, hsa-miR-615-5p, and hsa-miR-125a-5p to assess prognostic performance in overall survival (OS). promoter methylation and age were considered as cofactors. Integrated miRNA, DNA methylome, and transcriptome analysis were used to explore the functional impact of signature miRNAs.

Results: The 4-miRNA signature defined high-risk ( = 46, median OS: 15.8 months) and low-risk patients ( = 56, median OS: 20.7 months; univariable Cox proportional hazard analysis: hazard ratio [HR]: 1.8, 95% confidence interval [CI]: 1.14-2.83, = .01). The multivariable Cox proportional hazard model including the 4-miRNA signature ( = .161), promoter methylation ( < .001), and age ( = .034) significantly predicted OS (Log-rank < .0001). Likewise to clinical routine, analysis was performed for younger (≤60 years, = 50, median OS: 20.2 months) and older patients (>60 years, = 52, median OS: 15.8) separately. In younger patients, the 4-miRNA signature had prognostic value (HR: 1.92, 95% CI: 0.93-3.93, = .076). Particularly, younger, methylated, 4-miRNA signature low-risk patients ( = 18, median OS: 37.4 months) showed significantly improved survival, compared to other younger patients ( = 32, OS 18.5 months; HR: 0.33, 95% CI: 0.15-0.71, = .003). Integrated data analysis revealed 4-miRNA signature-associated genes and pathways.

Conclusion: The prognostic 4-miRNA signature in combination with promoter methylation improved risk stratification with the potential for therapeutic substratification, especially of younger patients.
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http://dx.doi.org/10.1093/noajnl/vdaa137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712804PMC
October 2020

Long-term outcome of stereotactic brachytherapy with temporary Iodine-125 seeds in patients with WHO grade II gliomas.

Radiat Oncol 2020 Dec 9;15(1):275. Epub 2020 Dec 9.

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

Background: This long-term retrospective analysis aimed to investigate the outcome and toxicity profile of stereotactic brachytherapy (SBT) in selected low-grade gliomas WHO grade II (LGGII) in a large patient series.

Methods: This analysis comprised 106 consecutive patients who received SBT with temporary Iodine-125 seeds for histologically verified LGGII at the University of Munich between March 1997 and July 2011. Investigation included clinical characteristics, technical aspects of SBT, the application of other treatments, outcome analyses including malignization rates, and prognostic factors with special focus on molecular biomarkers.

Results: For the entire study population, the 5- and 10-years overall survival (OS) rates were 79% and 62%, respectively, with a median follow-up of 115.9 months. No prognostic factors could be identified. Interstitial radiotherapy was applied in 51 cases as first-line treatment with a median number of two seeds (range 1-5), and a median total implanted activity of 21.8 mCi (range 4.2-43.4). The reference dose average was 54.0 Gy. Five- and ten-years OS and progression-free survival rates after SBT were 72% and 43%, and 40% and 23%, respectively, with a median follow-up of 86.7 months. The procedure-related mortality rate was zero, although an overall complication rate of 16% was registered. Patients with complications had a significantly larger tumor volume (p = 0.029).

Conclusion: SBT is a minimally invasive treatment modality with a favorable outcome and toxicity profile. It is both an alternative primary treatment method as well as an adjunct to open tumor resection in selected low-grade gliomas.
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http://dx.doi.org/10.1186/s13014-020-01719-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724805PMC
December 2020

[F18] FDG-PET/CT for manual or semiautomated GTV delineation of the primary tumor for radiation therapy planning in patients with esophageal cancer: is it useful?

Strahlenther Onkol 2020 Oct 26. Epub 2020 Oct 26.

Department of Radiotherapy and Radiation Oncology, Paracelsus Medical University (PMU), Landeskrankenhaus, Salzburg, Austria.

Background: Target volume definition of the primary tumor in esophageal cancer is usually based on computed tomography (CT) supported by endoscopy and/or endoscopic ultrasound and can be difficult given the low soft-tissue contrast of CT resulting in large interobserver variability. We evaluated the value of a dedicated planning [F18] FDG-Positron emission tomography/computer tomography (PET/CT) for harmonization of gross tumor volume (GTV) delineation and the feasibility of semiautomated structures for planning purposes in a large cohort.

Methods: Patients receiving a dedicated planning [F18] FDG-PET/CT (06/2011-03/2016) were included. GTV was delineated on CT and on PET/CT (GTV and GTV, respectively) by three independent radiation oncologists. Interobserver variability was evaluated by comparison of mean GTV and mean tumor lengths, and via Sørensen-Dice coefficients (DSC) for spatial overlap. Semiautomated volumes were constructed based on PET/CT using fixed standardized uptake values (SUV) thresholds (SUV30, 35, and 40) or background- and metabolically corrected PERCIST-TLG and Schaefer algorithms, and compared to manually delineated volumes.

Results: 45 cases were evaluated. Mean GTV and GTV were 59.2/58.0 ml, 65.4/64.1 ml, and 60.4/59.2 ml for observers A-C. No significant difference between CT- and PET/CT-based delineation was found comparing the mean volumes or lengths. Mean Dice coefficients on CT and PET/CT were 0.79/0.77, 0.81/0.78, and 0.8/0.78 for observer pairs AB, AC, and BC, respectively, with no significant differences. Mean GTV volumes delineated semiautomatically with SUV30/SUV35/SUV40/Schaefer's and PERCIST-TLG threshold were 69.1/23.9/18.8/18.6 and 70.9 ml. The best concordance of a semiautomatically delineated structure with the manually delineated GTV/GTV was observed for PERCIST-TLG.

Conclusion: We were not able to show that the integration of PET/CT for GTV delineation of the primary tumor resulted in reduced interobserver variability. The PERCIST-TLG algorithm seemed most promising compared to other thresholds for further evaluation of semiautomated delineation of esophageal cancer.
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http://dx.doi.org/10.1007/s00066-020-01701-0DOI Listing
October 2020

Dual PET Imaging of an H3K27M-Mutant Glioma With 18F-GE-180 and 18F-FET PET.

Clin Nucl Med 2020 Dec;45(12):992-993

Neuropathology.

A 25-year-old man presented with headache and intracranial pressure symptoms. On MRI, an intracranial lesion was detected in the right thalamus with exophytic growth into the third ventricle and inhomogeneous contrast enhancement without necrosis. Dual amino acid (F-FET) and TSPO (F-GE-180) PET imaging showed high tumor-to-background ratios in both scans and a short time-to-peak in F-FET uptake dynamics. Biopsy revealed a diffuse midline glioma, H3K27M-mutant (WHO grade IV), a novel entity in the 2016 WHO classification with poor clinical outcome. Our case shows that the highly aggressive features of this tumor entity can be visualized in vivo by both PET modalities.
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http://dx.doi.org/10.1097/RLU.0000000000003331DOI Listing
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

Brain Necrosis in Adult Patients After Proton Therapy: Is There Evidence for Dependency on Linear Energy Transfer?

Int J Radiat Oncol Biol Phys 2021 Jan 7;109(1):109-119. Epub 2020 Sep 7.

Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Purpose: To investigate if radiographic imaging changes defined as necrosis correlate with regions in the brain with elevated linear energy transfer (LET) for proton radiation therapy treatments with partial brain involvement in central nervous system and patients with head and neck cancer.

Methods And Materials: Fifty patients with head and neck, skull base, or intracranial tumors who underwent proton therapy between 2004 to 2016 with a minimum prescription dose of 59.4 Gy (relative biological effectiveness) and with magnetic resonance imaging changes indicative of brain necrosis after radiation therapy were retrospectively reviewed. Each treatment plan was recalculated using Monte Carlo simulations to provide accurate dose distributions as well as 3-dimensional distributions of LET. To assess the effect of LET on radiographic imaging changes several voxel-based analyses were performed.

Results: In this patient cohort, LET adjusted for dose was not found to be associated with risk of brain necrosis.

Conclusions: A voxel-based analysis of brain necrosis as an endpoint is difficult owing to uncertainties in the origin of necrosis, timing of imaging, variability in patient specific radiosensitivity, and the simultaneous effect of dose and LET. Even though it is expected that the LET and thus relative biological effectiveness increases at the end of range, effects in patients might be small compared with interpatient variability of radiosensitivity and might be obscured by other confounding factors.
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http://dx.doi.org/10.1016/j.ijrobp.2020.08.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736370PMC
January 2021

SARS-CoV-2 prevalence in an asymptomatic cancer cohort - results and consequences for clinical routine.

Radiat Oncol 2020 Jul 9;15(1):165. Epub 2020 Jul 9.

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

Background: Starting in December 2019, the current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confronts the world with an unprecedented challenge. With no vaccine or drug being currently available to control the pandemic spread, prevention and PCR (Polymerase chain reaction) testing becomes a crucial pillar of medical systems. Aim of the present study was to report on the first results of the measures taken in a large German Department of Radiation Oncology, including PCR testing of asymptomatic cancer patients.

Methods: Pandemic-adapted hygiene regulations and prevention measures for patients and staff were implemented. A visiting ban on both wards was implemented from the beginning and medical staff and patients were required to wear face masks at all times. The waiting rooms were rearranged to ensure distance between patients of at least 1.5 m. Clinical follow up was mainly done by telephone and all patients had to complete a questionnaire regarding symptoms and contacts with COVID-19 patients before entering our department. Educational documents were created for patients to raise awareness of symptoms and avoidance strategies for interactions with other people. Indications for therapy and fractionation schemes were adapted when possible. In a subsequent step, all new asymptomatic patients were tested via nasopharyngeal swab at our screening station shortly before their simulation CT.

Results: All these measures and implementations have been well accepted semiquantitatively measured by the consent received from patients and staff. Regarding the PCR testing, only 1 out of 139 asymptomatic patients of our cohort so far tested positive for SARS-CoV-2, reflecting a prevalence of 0.72% in this cancer patient population. Up to this point no staff members was tested positive. The start of the treatment for the PCR-positive patient was deferred for 2 weeks.

Conclusion: Due to the pandemic-adapted implementations, our department seems well prepared during this crisis. The initial screening helps to identify asymptomatic COVID-19 patients in order to protect other patients and our staff from infection and the observed PCR prevalence is in line with comparable studies. A regular PCR testing (e.g. twice a week) of all patients and staff would in principle be desirable but is limited due to testing capacities at present.
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http://dx.doi.org/10.1186/s13014-020-01609-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344028PMC
July 2020

Heart sparing radiotherapy in breast cancer: the importance of baseline cardiac risks.

Radiat Oncol 2020 May 24;15(1):117. Epub 2020 May 24.

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

Background: Patients with left-sided breast cancer have an increased risk of cardiovascular disease (CVD) after radiotherapy (RT). While the awareness of cardiac toxicity has increased enormously over the last decade, the role of individual baseline cardiac risks has not yet been systematically investigated. Aim of the present study was to evaluate the impact of baseline CVD risks on radiation-induced cardiac toxicity.

Methods: Two hundred ten patients with left-sided breast cancer treated in the prospective Save-Heart Study using a deep inspiration breath-hold (DIBH) technique were analysed regarding baseline risk factors for CVD. Three frequently used prediction tools (Procam, Framingham and Reynolds score) were applied to evaluate the individual CVD risk profiles. Moreover, 10-year CVD excess absolute risks (EAR) were estimated using the individual mean heart dose (MHD) of treatment plans in free breathing (FB) and DIBH.

Results: The individual baseline CVD risk factors had a strong impact on the 10-year cumulative CVD risk. The mean baseline risks of the non-diabetic cohort (n = 200) ranged from 3.11 to 3.58%, depending on the risk estimation tool. A large number of the non-diabetic patients had a very low 10-year CVD baseline risk of ≤1%; nevertheless, 8-9% of patients reached ≥10% baseline 10-year CVD risk. In contrast, diabetic patients (n = 10) had significantly higher baseline CVD risks (range: 11.76-24.23%). The mean 10-year cumulative risk (Framingham score) following RT was 3.73% using the DIBH-technique (MHD:1.42Gy) and 3.94% in FB (MHD:2.33Gy), after adding a 10-year-EAR of + 0.34%(DIBH) and + 0.55%(FB) to the baseline risks, respectively. Smoking status was one of the most important and modifiable baseline risk factors. After DIBH-RT, the 182 non-smoking patients had a mean 10-year cumulative risk of 3.55% (3.20% baseline risk, 0.35% EAR) as compared to 6.07% (5.60% baseline risk, 0.47% EAR) for the 28 smokers.

Conclusion: In the present study, all CVD prediction tools showed comparable results and could easily be integrated into daily clinical practice. A systematic evaluation and screening helps to identify high-risk patients who may benefit from primary prevention. This could result in an even higher benefit than from heart-sparing irradiation techniques alone.
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http://dx.doi.org/10.1186/s13014-020-01520-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245801PMC
May 2020

First statement on preparation for the COVID-19 pandemic in large German Speaking University-based radiation oncology departments.

Radiat Oncol 2020 Apr 7;15(1):74. Epub 2020 Apr 7.

Department of Radiation Oncology, Technical University of Munich (TUM), Klinikum rechts der Isar, Ismaninger Straße 22, D-81675 München, Munich, Germany.

The COVID-19 pandemic is challenging modern radiation oncology. At University Hospitals, we have a mandate to offer high-end treatments to all cancer patients. However, in times of crisis we must learn to prioritize resources, especially personnel. Compromising oncological outcome will blur all statistics, therefore all measures must be taken with great caution. Communication with our neighboring countries, within societies and between departments can help meet the challenge. Here, we report on our learning system and preparation measures to effectively tackle the COVID-19 challenge in University-Based Radiation Oncology Departments.
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http://dx.doi.org/10.1186/s13014-020-01527-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136995PMC
April 2020

Optimizing the Analytical Value of Oncology-Related Data Based on an In-Memory Analysis Layer: Development and Assessment of the Munich Online Comprehensive Cancer Analysis Platform.

J Med Internet Res 2020 04 17;22(4):e16533. Epub 2020 Apr 17.

Comprehensive Cancer Center, Ludwig-Maximilians-Universität München, Munich, Germany.

Background: Many comprehensive cancer centers incorporate tumor documentation software supplying structured information from the associated centers' oncology patients for internal and external audit purposes. However, much of the documentation data included in these systems often remain unused and unknown by most of the clinicians at the sites.

Objective: To improve access to such data for analytical purposes, a prerollout of an analysis layer based on the business intelligence software QlikView was implemented. This software allows for the real-time analysis and inspection of oncology-related data. The system is meant to increase access to the data while simultaneously providing tools for user-friendly real-time analytics.

Methods: The system combines in-memory capabilities (based on QlikView software) with innovative techniques that compress the complexity of the data, consequently improving its readability as well as its accessibility for designated end users. Aside from the technical and conceptual components, the software's implementation necessitated a complex system of permission and governance.

Results: A continuously running system including daily updates with a user-friendly Web interface and real-time usage was established. This paper introduces its main components and major design ideas. A commented video summarizing and presenting the work can be found within the Multimedia Appendix.

Conclusions: The system has been well-received by a focus group of physicians within an initial prerollout. Aside from improving data transparency, the system's main benefits are its quality and process control capabilities, knowledge discovery, and hypothesis generation. Limitations such as run time, governance, or misinterpretation of data are considered.
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http://dx.doi.org/10.2196/16533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195671PMC
April 2020

Stereotactic radiosurgery combined with targeted/ immunotherapy in patients with melanoma brain metastasis.

Radiat Oncol 2020 Feb 14;15(1):37. Epub 2020 Feb 14.

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

Background: There is limited data on the use of targeted or immunotherapy (TT/IT) in combination with single fraction stereotactic radiosurgery (SRS) in patients with melanoma brain metastasis (MBM). Therefore, we analyzed the outcome and toxicity of SRS alone compared to SRS in combination with TT/IT.

Methods: Patients with MBM treated with single session SRS at our department between 2014 and 2017 with a minimum follow-up of 3 months after first SRS were included. The primary endpoint of this study was local control (LC). Secondary endpoints were distant intracranial control, radiation necrosis-free survival (RNFS), and overall survival (OS). The local/ distant intracranial control rates, RNFS and OS were analyzed using the Kaplan-Meier method. The log-rank test was used to test differences between groups. Cox proportional hazard model was performed for univariate continuous variables and multivariate analyses.

Results: Twenty-eight patients (17 male and 11 female) with 52 SRS-lesions were included. The median follow-up was 19 months (range 14-24 months) after first SRS. Thirty-six lesions (69.2%) were treated with TT/IT simultaneously (4 weeks before and 4 weeks after SRS), while 16 lesions (30.8%) were treated with SRS alone or with sequential TT/IT. The 1-year local control rate was 100 and 83.3% for SRS with TT/IT and SRS alone (p = 0.023), respectively. The estimated 1-year RNFS was 90.0 and 82.1% for SRS in combination with TT/IT and SRS alone (p = 0.935). The distant intracranial control rate after 1 year was 47.7 and 50% for SRS in combination with TT/IT and SRS alone (p = 0.933). On univariate analysis, the diagnosis-specific Graded Prognostic Assessment including the BRAF status (Melanoma-molGPA) was associated with a significantly improved LC. Neither gender nor SRS-PTV margin had a prognostic impact on LC. V10 and V12 were significantly associated with RNFS (p < 0.001 and p = 0.004).

Conclusion: SRS with simultaneous TT/IT significantly improved LC with no significant difference in radiation necrosis rate. The therapy combination appears to be effective and safe. However, prospective studies on SRS with simultaneous TT/IT are necessary and ongoing.

Trial Registration: The institutional review board approved this analysis on 10th of February 2015 and all patients signed informed consent (UE nr. 128-14).
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http://dx.doi.org/10.1186/s13014-020-1485-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023694PMC
February 2020