Stereotactic radiosurgery versus whole-brain radiotherapy in patients with 4-10 brain metastases: A nonrandomized controlled trial.

BACKGROUND AND PURPOSE: There is no randomized evidence comparing whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) in the treatment of multiple brain metastases. This prospective nonrandomized controlled single arm trial attempts to reduce the gap until prospective randomized controlled trial results are available. MATERIAL AND METHODS: We included patients with 4-10 brain metastases and ECOG performance status ≤ 2 from all histologies except small-cell lung cancer, germ cell tumors, and lymphoma. The retrospective WBRT-cohort was selected 2:1 from consecutive patients treated within 2012-2017. Propensity-score matching was performed to adjust for confounding factors such as sex, age, primary tumor histology, dsGPA score, and systemic therapy. SRS was performed using a LINAC-based single-isocenter technique employing prescription doses from 15-20Gyx1 at the 80% isodose line. The historical control consisted of equivalent WBRT dose regimens of either 3Gyx10 or 2.5Gyx14. RESULTS: Patients were recruited from 2017-2020, end of follow-up was July 1st, 2021. 40 patients were recruited to the SRS-cohort and 70 patients were eligible as controls in the WBRT-cohort. Median OS, and iPFS were 10.4 months (95%-CI 9.3-NA) and 7.1 months (95%-CI 3.9-14.2) for the SRS-cohort, and 6.5 months (95%-CI 4.9-10.4), and 5.9 months (95%-CI 4.1-8.8) for the WBRT-cohort, respectively. Differences were non-significant for OS (HR: 0.65; 95%-CI 0.40-1.05; P =.074) and iPFS (P =.28). No grade III toxicities were observed in the SRS-cohort. CONCLUSION: This trial did not meet its primary endpoint as the OS-improvement of SRS compared to WBRT was non-significant and thus superiority could not be proven. Prospective randomized trials in the era of immunotherapy and targeted therapies are warranted.

Stereotactic radiosurgery and combined immune checkpoint therapy with ipilimumab and nivolumab in patients with melanoma brain metastases: A retrospective monocentric toxicity analysis.

Purpose and objective: Adding stereotactic radiosurgery (SRS) to combined immune checkpoint therapy with ipilimumab and nivolumab (IPI + NIVO) has led to promising results for patients with melanoma brain metastases (MBM). This study retrospectively analyzes the toxicity profile depending on the timing of SRS with regard to IPI + NIVO. Materials and methods: For this study, the clinical database was searched for all patients with MBM who were treated with SRS and IPI + NIVO. The patients were separated into three groups: group A completed IPI + NIVO (usually up to four cycles) >14 days before SRS, in group B IPI + NIVO was initiated>14 days after SRS, and group C received SRS concurrently to IPI + NIVO. Treatment related toxicity was obtained from clinical and neuroradiological records. Analyses were performed using the Fisher-Yates-test. Results: 31 patients were assessed including six (19.4 %), seven (22.6 %) and 18 (58.1 %) patients, in groups A, B and C, respectively. Baseline prognostic markers between groups were balanced. In total, five (16.1 %) patients experienced neurological grade 3 toxicities related to SRS. All of these five patients were in group C, which was near-significantly correlated with a risk for grade 3 toxicities (p = 0.058). Post-hoc analyses showed that a maximum time period of seven days between SRS and IPI + NIVO was significantly correlated with grade 3 toxicity (p = 0.048). Conclusion: Application of SRS to IPI + NIVO within a seven-day span was related to higher toxicity rates in this retrospective analysis. After previous studies focused on immune checkpoint monotherapies with SRS and declared it as safe, this study indicates that concomitant application of IPI + NIVO and SRS might increase side effects. Prospective validation is warranted to corroborate these findings.

Patient-specific transfer learning for auto-segmentation in adaptive 0.35 T MRgRT of prostate cancer: a bi-centric evaluation.

BACKGROUND: Online adaptive radiation therapy (RT) using hybrid magnetic resonance linear accelerators (MR-Linacs) can administer a tailored radiation dose at each treatment fraction. Daily MR imaging followed by organ and target segmentation adjustments allow to capture anatomical changes, improve target volume coverage, and reduce the risk of side effects. The introduction of automatic segmentation techniques could help to further improve the online adaptive workflow by shortening the re-contouring time and reducing intra- and inter-observer variability. In fractionated RT, prior knowledge, such as planning images and manual expert contours, is usually available before irradiation, but not used by current artificial intelligence-based autocontouring approaches. PURPOSE: The goal of this study was to train convolutional neural networks (CNNs) for automatic segmentation of bladder, rectum (organs at risk, OARs), and clinical target volume (CTV) for prostate cancer patients treated at 0.35 T MR-Linacs. Furthermore, we tested the CNNs generalization on data from independent facilities and compared them with the MR-Linac treatment planning system (TPS) propagated structures currently used in clinics. Finally, expert planning delineations were utilized for patient- (PS) and facility-specific (FS) transfer learning to improve auto-segmentation of CTV and OARs on fraction images. METHODS: In this study, data from fractionated treatments at 0.35 T MR-Linacs were leveraged to develop a 3D U-Net-based automatic segmentation. Cohort C1 had 73 planning images and cohort C2 had 19 planning and 240 fraction images. The baseline models (BMs) were trained solely on C1 planning data using 53 MRIs for training and 10 for validation. To assess their accuracy, the models were tested on three data subsets: (i) 10 C1 planning images not used for training, (ii) 19 C2 planning, and (iii) 240 C2 fraction images. BMs also served as a starting point for FS and PS transfer learning, where the planning images from C2 were used for network parameter fine tuning. The segmentation output of the different trained models was compared against expert ground truth by means of geometric metrics. Moreover, a trained physician graded the network segmentations as well as the segmentations propagated by the clinical TPS. RESULTS: The BMs showed dice similarity coefficients (DSC) of 0.88(4) and 0.93(3) for the rectum and the bladder, respectively, independent of the facility. CTV segmentation with the BM was the best for intermediate- and high-risk cancer patients from C1 with DSC=0.84(5) and worst for C2 with DSC=0.74(7). The PS transfer learning brought a significant improvement in the CTV segmentation, yielding DSC=0.72(4) for post-prostatectomy and low-risk patients and DSC=0.88(5) for intermediate- and high-risk patients. The FS training did not improve the segmentation accuracy considerably. The physician's assessment of the TPS-propagated versus network-generated structures showed a clear advantage of the latter. CONCLUSIONS: The obtained results showed that the presented segmentation technique has potential to improve automatic segmentation for MR-guided RT.

Primary radiation therapy in stage I/II indolent orbital lymphoma - a comprehensive retrospective recurrence and toxicity analysis.

PURPOSE OR OBJECTIVE: To provide a comprehensive recurrence and toxicity analysis of patients treated with radiotherapy alone for stage I/II (Ann-Arbor classification) indolent orbital lymphoma. MATERIAL AND METHODS: We retrospectively reviewed the medical charts of 46 patients (and 51 orbits) treated at our centre with radiotherapy between 1995 and 2012 for biopsy-proven stage I/IIE primary orbital lymphomas. We evaluated treatment response and performed a comprehensive toxicity analysis with correlation to delivered radiation dose. RESULTS: At diagnosis, the median age was 63.5 years (range: 20-92). At initial diagnosis 43 and 3 patients had unilateral, synchronous bilateral involvement while there were 2 cases of contralateral metachronous failure. The predominant histological subtype was extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in 42 (91.3%), follicular in 1 (2.2%), lymphoplasmacytic lymphoma in 1 (2.2%) and other indolent histology in 2 (4.3%) patients. Most lymphomas were located in the conjunctiva (18/35.3%) or eyelids (18/35.3%). Thirty-eight (82.6%) patients presented with stage I while 8/46 (17.4%) with stage II disease. The median radiation dose was 39.6 Gy (range: 21.6-48.6 Gy) delivered in 1.8-2 Gy single fractions. At a median follow-up of 83 months (range: 7-258 months), the complete remission rate was 98%. A local relapse was observed in 2/51 (3.9%) orbits and 4/46 (8.7%) patients had systemic relapse. The 5- and 10-year PFS rates were 79.2% (95% CI: 73.0%-85.4%) and 67.6% (95% CI: 59.4%-75.8%); 5- and 10-year OS was 83.6% (95% CI: 77.9%-89.3%) and 76.5% (95% CI: 69.4%-83.6%), respectively. In total, 66 acute toxicity events (all-grade) were observed: 5/51 (9.8%) ≥G2 acute conjunctivitis, 2/51 (3.9%) cases of G2 acute keratitis, 1/51 (2%) cases of ≥G2 ophthalmagia and 12/51 (23.5%) cases of ≥G2 xerophthalmia. Furthermore, 45 chronic adverse events were observed in 34/51 (66.7%) irradiated orbits with 30 late adverse events attributed to cataract. CONCLUSION: Our analysis confirms the role of radiotherapy alone at lower doses in the treatment of indolent orbital lymphomas. Further research is required to assess the efficacy of ultra-low-dose radiotherapy and anti-CD20 monoclonal antibodies to further mitigate long-term sequelae.

MR-guided SBRT boost for patients with locally advanced or recurrent gynecological cancers ineligible for brachytherapy: feasibility and early clinical experience.

BACKGROUND AND PURPOSE: Chemoradiotherapy (CRT) followed by a brachytherapy (BT) boost is the standard of care for patients with locally advanced or recurrent gynecological cancer (LARGC). However, not every patient is suitable for BT. Therefore, we investigated the feasibility of an MR-guided SBRT boost (MRg-SBRT boost) following CRT of the pelvis. MATERIAL AND METHODS: Ten patients with LARGC were analyzed retrospectively. The patients were not suitable for BT due to extensive infiltration of the pelvic wall (10%), other adjacent organs (30%), or both (50%), or ineligibility for anesthesia (10%). Online-adaptive treatment planning was performed to control for interfractional anatomical changes. Treatment parameters and toxicity were evaluated to assess the feasibility of MRg-SBRT boost. RESULTS: MRg-SBRT boost was delivered to a median total dose of 21.0 Gy in 4 fractions. The median optimized PTV (PTVopt) size was 43.5ccm. The median cumulative dose of 73.6Gy10 was delivered to PTVopt. The cumulative median D2ccm of the rectum was 63.7 Gy; bladder 72.2 Gy; sigmoid 65.8 Gy; bowel 59.9 Gy (EQD23). The median overall treatment time/fraction was 77 min, including the adaptive workflow in 100% of fractions. The median duration of the entire treatment was 50 days. After a median follow-up of 9 months, we observed no CTCAE ≥ °II toxicities. CONCLUSION: These early results report the feasibility of an MRg-SBRT boost approach in patients with LARGC, who were not candidates for BT. When classical BT-OAR constraints are followed, the therapy was well tolerated. Long-term follow-up is needed to validate the results.

Combining inter-observer variability, range and setup uncertainty in a variance-based sensitivity analysis for proton therapy.

Margin concepts in proton therapy aim to ensure full dose coverage of the clinical target volume (CTV) in presence of setup and range uncertainty. Due to inter-observer variability (IOV), the CTV itself is uncertain. We present a framework to evaluate the combined impact of IOV, setup and range uncertainty in a variance-based sensitivity analysis (SA). For ten patients with skull base meningioma, the mean calculation time to perform the SA including 1.6 × 104 dose recalculations was 59 min. For two patients in this dataset, IOV had a relevant impact on the estimated CTV D95% uncertainty.

Multimodal therapy of cavernous sinus meningioma: Impact of surgery and 68Ga-DOTATATE PET-guided radiation therapy on tumor control and functional outcome.

BACKGROUND: Functional preservation in patients with WHO grade I meningioma involving the cavernous sinus (CSM) is crucial for long-term tumor control. Concise data on the functional outcome of an interdisciplinary, multimodal treatment are scarce. We analyzed functional outcome and tumor control in CSM patients following maximal safe resection (MSR), fractionated stereotactic radiotherapy (FSRT), or combination of them, retrospectively. METHODS: Patients with WHO grade I CSM treated between 2003 and 2017 were included. Prior to FSRT, a 68Ga-DOTATATE PET/CT was performed for radiation planning. Progression-free survival (PFS) was analyzed using Kaplan-Meier method and log-rank test was performed to test differences between groups. Visual function was analyzed at baseline and follow-up. RESULTS: Eighty-five patients were included. MSR alone was performed in 48 patients (group A), MSR followed by FSRT in 25 patients (group B), and FSRT alone in 12 patients (group C). Intracranial tumor volumes were higher in A and B compared to C (median 9.2/10.8/4.3 ccm for A/B/C, P = .023). Median follow-up was 47/46/45 months and PFS at 5 years 55.7%, 100%, and 100% in A/B/C, respectively (P < .001). Optic nerve compression was more common in A (91.7%) and B (84.0%) than C (16.7%), P < .001. Post-therapeutic new onset or deterioration of double vision was observed in 29% (A), 17% (B), and 0% (C). CONCLUSION: Personalized treatment strategies for CSM are essential to control space-occupying or functionally compromising lesions. The additional potential side effect of radiotherapy seems to be justified under the aspect of longer tumor control with low functional risk. Without space-occupying effect of CSM, FSRT alone is reasonably possible.

Multifocal high-grade glioma radiotherapy safety and efficacy.

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 cm3. Median volume of the PTV was 425.7 cm3 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.

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

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.

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

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.

Maximum standardized uptake value of primary tumor (SUVmax_PT) and horizontal range between two most distant PET-positive lymph nodes predict patient outcome in inoperable stage III NSCLC patients after chemoradiotherapy.

BACKGROUND: 18F-FDG-positron emission tomography (PET)/computed tomography (CT) is a standard for initial staging in patients with locally advanced stage III non-small cell lung cancer (NSCLC). We evaluated a PET/CT staging score to characterize disease extension and patient outcome in this disease. METHODS: Ninety-nine consecutive patients with NSCLC stage IIIA-B (UICC 7th edition), who underwent 18F-FDG-PET/CT before the start of chemoradiotherapy (CRT) were analyzed. Maximum standardized uptake value of primary tumor (SUVmax_PT) and range between two most distant PET-positive (SUV ≥2.5) lymph nodes in two directions were analyzed for their correlation with patient outcome. The vertical distance was defined as A- and the horizontal as a B-line. RESULTS: According to the results of univariate analysis, score included the SUVmax_PT and horizontal B-line, patients were divided into three risk subgroups: low, intermediate and high-risk subgroups. Subgroups were defined as SUVmax_PT <8 and B-line <3.7 cm, SUVmax_PT >8 or B-line >3.7 cm and SUVmax_PT >8 plus B-line >3.7 cm, respectively. Twenty-eight (28%), 45 (46%) and 26 (26%) patients were assigned to the low, intermediate and high-risk subgroup, respectively. Median event-free survival (EFS) in low, intermediate and high-risk subgroups was 16 (95% CI: 7-25), 13 (95% CI: 12-15) and 10 (95% CI: 7-13) months (P=0.002, log-rank test). Median OS in the low, intermediate and high-risk subgroups was 40 (95% CI: 11-69), 23 (95% CI: 15-31) and 14 (95% CI: 13-14) months (P=0.0001, log-rank test). In the multivariate analysis, SUV, B-line and PET/CT score were significantly associated with EFS [harard ratio (HR) 2.12 (95% CI: 1.27-3.55) and intermediate risk HR 2.01 (95% CI: 1.13-3.59), P=0.003] and OS [high-risk HR 2.79 (95% CI: 1.16-4.55) and intermediate risk HR 2.30 (95% CI: 1.58-4.94), P=0.001]. CONCLUSIONS: A PET/CT score was developed for inoperable stage III NSCLC patients treated with CRT and was an independent predictor of patient outcome in the single-center cohort.

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

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).

Single isocenter stereotactic radiosurgery for patients with multiple brain metastases: dosimetric comparison of VMAT and a dedicated DCAT planning tool.

BACKGROUND: In this dosimetric study, a dedicated planning tool for single isocenter stereotactic radiosurgery for multiple brain metastases using dynamic conformal arc therapy (DCAT) was compared to standard volumetric modulated arc therapy (VMAT). METHODS: Twenty patients with a total of 66 lesions who were treated with the DCAT tool were included in this study. Single fraction doses of 15-20 Gy were prescribed to each lesion. Patients were re-planned using non-coplanar VMAT. Number of monitor units as well as V4Gy, V5Gy and V8Gy were extracted for every plan. Using a density-based clustering algorithm, V10Gy and V12Gy and the volume receiving half of the prescribed dose were extracted for every lesion. Gradient indices and conformity indices were calculated. The correlation of the target sphericity, a measure of how closely the shape of the target PTV resembles a sphere, to the difference in V10Gy and V12Gy between the two techniques was assessed using Spearman's correlation coefficient. RESULTS: The automated DCAT planning tool performed significantly better in terms of all investigated metrics (p < 0.05), in particular healthy brain sparing (V10Gy: median 3.2 cm3 vs. 4.9 cm3), gradient indices (median 5.99 vs. 7.17) and number of monitor units (median 4569 vs. 5840 MU). Differences in conformity indices were minimal (median 0.75 vs. 0.73) but still significant (p < 0.05). A moderate correlation between PTV sphericity and the difference of V10Gy and V12Gy between the two techniques was found (Spearman's rho = 0.27 and 0.30 for V10Gy and V12Gy, respectively, p < 0.05). CONCLUSIONS: The dedicated DCAT planning tool performed better than VMAT in terms of healthy brain sparing and treatment efficiency, in particular for nearly spherical lesions. In contrast, VMAT can be superior in cases with irregularly shaped lesions.

Medulloblastoma in adults : A retrospective single institution analysis.

PURPOSE: Adult medulloblastoma is a rare disease treated according to the current pediatric treatment guidelines. This retrospective analysis investigated the clinical outcomes and prognostic factors of adult medulloblastoma patients, who received multimodal therapy at our institution. METHODS: Treatment charts of all patients over the age of 15 years of age with de novo medulloblastoma, who had been treated at our institution between 2001 and 2014, were retrospectively analyzed. Patients' demographic parameters, initial symptoms, treatment modalities, toxicities, and survival outcomes were investigated. RESULTS: In all, 21 patients with a median age of 30.2 years were identified. The most frequent histologies were desmoplastic and classic, and the most common molecular subtype was sonic hedgehog (SHH). After tumor resection, all patients received craniospinal irradiation (median dose 35.2 Gy) and a boost to the posterior fossa (median dose 19.8 Gy). Simultaneous chemotherapy with vincristine was given to 20 patients and sequential chemotherapy to 15 patients. The most common side effects were hematological toxicities. Median overall survival (OS) has not been reached after a median follow-up of 92 months. Estimated 5­ and 10-year OS was 89 and 80%, respectively. Estimated 5­ and 10-year progression-free survival (PFS) was 89 and 81%, respectively. In univariate analysis, a shorter interval between tumor resection and end of irradiation was significantly associated with improved OS and PFS, anaplastic histology with worse OS and PFS. CONCLUSIONS: The combined modality treatment showed a good outcome in adults with medulloblastoma. Treatment time was revealed to be prognostic and should be kept as short as possible.

Radiotherapy of spinal cord gliomas : A retrospective mono-institutional analysis.

BACKGROUND: Due to the rarity of spinal cord gliomas, no consensus has been reached regarding the optimal treatment strategy. The aim of the present retrospective study was to identify patient and tumor characteristics and to evaluate the effectiveness of radiotherapy within this setting. PATIENTS AND METHODS: Patients diagnosed with spinal cord gliomas between 2003 and 2013 and treated at the Department of Radiation Oncology, University of Munich, were retrospectively analyzed. Overall survival was estimated with the Kaplan-Meier method and univariate analysis was performed by log-rank testing. RESULTS: A total of 16 patients were identified. The cohort consisted of seven primary spinal cord gliomas and eight cases of metastases of cerebral gliomas. Median follow-up was 42 months and median total radiation dose was 45.0 Gy. In all, 62.5 % of patients received a simultaneous chemotherapy with temozolomide. The median overall survival was 6 months (95% CI: 0-27.5 months). Surgical resection of the tumor was a significant predictor of improved survival, compared with radiotherapy alone (p = 0.001). Patients with the diagnosis of a primary spinal cord glioma survived significantly longer than those presenting with a metastatic deposit from a cerebral glioma (p < 0.001). A statistically significant dose-response relationship at dose levels of ≥ 45 Gy vs. < 45 Gy could be derived (p < 0.001). Simultaneous chemotherapy did not influence survival outcome. CONCLUSION: Despite the aggressive treatment in the present study, the prognosis for spinal cord gliomas was still poor, with a median overall survival of 6 months. To the best of our knowledge, this is the largest study reporting the results of simultaneous chemoradiation in spinal cord gliomas. A combined chemoradiation treatment seems feasible and can be considered as a new treatment option in the management of spinal cord gliomas.

Assessment of diabetic retinopathy using nonmydriatic ultra-widefield scanning laser ophthalmoscopy (Optomap) compared with ETDRS 7-field stereo photography.

OBJECTIVE: To compare the diagnostic properties of a nonmydriatic 200° ultra-widefield scanning laser ophthalmoscope (SLO) versus mydriatic Early Treatment of Diabetic Retinopathy Study (ETDRS) 7-field photography for diabetic retinopathy (DR) screening. RESEARCH DESIGN AND METHODS: A consecutive series of 212 eyes of 141 patients with different levels of DR were examined. Grading of DR and clinically significant macular edema (CSME) from mydriatic ETDRS 7-field stereo photography was compared with grading obtained by Optomap Panoramic 200 SLO images. All SLO scans were performed through an undilated pupil, and no additional clinical information was used for evaluation of all images by the two independent, masked, expert graders. RESULTS: Twenty-two eyes from ETDRS 7-field photography and 12 eyes from Optomap were not gradable by at least one grader because of poor image quality. A total of 144 eyes were analyzed regarding DR level and 155 eyes regarding CSME. For ETDRS 7-field photography, 22 eyes (18 for grader 2) had no or mild DR (ETDRS levels ≤ 20) and 117 eyes (111 for grader 2) had no CSME. A highly substantial agreement between both Optomap DR and CSME grading and ETDRS 7-field photography existed with κ = 0.79 for DR and 0.73 for CSME for grader 1, and κ = 0.77 (DR) and 0.77 (CSME) for grader 2. CONCLUSIONS: Determination of CSME and grading of DR level from Optomap Panoramic 200 nonmydriatic images show a positive correlation with mydriatic ETDRS 7-field stereo photography. Both techniques are of sufficient quality to assess DR and CSME. Optomap Panoramic 200 images cover a larger retinal area and therefore may offer additional diagnostic properties.