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Copyright of HNO is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To dosimetrically compare applicator-guided intensity-modulated proton therapy (IMPT) and multichannel brachytherapy (MC-BRT) for vaginal vault irradiation (VVI) with special focus on dose to organs at risk (OARs) and normal tissues. Ten patients with uterine confined endometrial cancer who received adjuvant vaginal cuff brachytherapy were included in this study. For each patient an additional IMPT treatment plan was created using the same computed tomography dataset and contours segmented for MC-BRT plans. Clinical target volume (CTV) was defined as the proximal 3.5 cm of the vagina including the entire thickness of vaginal wall. Planning target volume for IMPT plans was generated from the CTV with an addition isotropic 3 mm margin. OARs included rectum, bladder, sigmoid, small bowel and femoral heads. The prescribed dose was 21 Gy in 3 fractions. For simplicity, all doses were expressed in Gy and a constant relative biological effectiveness of 1.1 was used for IMPT plans. Plan comparison was performed using dose-volume histogram and treatment planning parameters. A significant improvement of the D98% coverage for CTV was reached by the applicator-guided IMPT plans (p < 0.01). IMPT also provided a dose reduction in all OARs except for femoral heads due to the lateral beam direction, especially significant reduction of V5Gy, D2cc, D0.1 cc, Dmean, V95% values for the rectum and Dmean, D0.1 cc to bladder, sigmoid, small bowel. Additionally, IMPT plans showed a significant reduction of integral dose to normal tissue with respect to MC-BRT (221.5 cGy.L vs. 653.6 cGy.L, p < 0.01). Applicator-guided IMPT has the potential for improving plan quality in VVI while maintaining the high conformity afforded by the state-of-the-art intracavitary brachytherapy. [ABSTRACT FROM AUTHOR]

Purpose: Optimization of local therapies in synovial sarcoma (SS) considered unresectable at diagnosis is needed. We evaluated the effects of neoadjuvant versus adjuvant radiation versus surgery only on long-term outcomes. Methods: Patients with macroscopic SS tumors before chemotherapy (IRS-group-III) in the trials CWS-81, CWS-86, CWS-91, CWS-96, CWS-2002-P and SoTiSaR-registry were analyzed. Local therapies were scheduled after 3 neoadjuvant chemotherapy cycles. Results: Median age of 145 patients was 14.5 years. 106 survivors had median follow-up of 7.0 years. Tumor site was 96 extremities, 19 head–neck, 16 shoulder/hip, 14 trunk. Tumors were < 3 cm in 16, 3–5 cm in 28, 5–10 cm in 55, > 10 cm in 34 patients. In a secondary resection during chemotherapy, R0-status was accomplished in 82, R1 in 30, R2 in 21 (12 missing). Radiotherapy was administered to 115 (R0 61, R1 29, R2 20, missing 5), thereof 57 before and 52 after tumor resection. 23 were treated with surgery only. For all patients, 5 year event-free (EFS) and overall survival (OS) was 68.9% ± 7.6 (95%CI) and 79.1% ± 6.9. To establish independent significance, tumor site, size, surgical results and sequencing of local therapies were analyzed in a Cox regression analysis. Variables associated with EFS and OS are site, size and sequencing of local therapies. Variables associated with local recurrence are site, surgical results and sequencing of local therapies. The only variable associated with suffering metastatic recurrence is tumor size. Conclusion: Differences in sequencing of local therapy procedures are independently associated with outcomes. Best local control is achieved when tumors are irradiated pre-operatively and undergo R0 or R1 resection thereafter. [ABSTRACT FROM AUTHOR]

Introduction: Standards for chemotherapy against choroid plexus tumors (CPT) have not yet been established. Methods: CPT-SIOP-2000 (NCT00500890) was an international registry for all CPT nesting a chemotherapy randomization for high-risk CPT with Carboplatin/Etoposide/Vincristine (CarbEV) versus Cyclophosphamide/Etoposide/Vincristine (CycEV). Patients older than three years were recommended to receive irradiation: focal fields for non-metastatic CPC, incompletely resected atypical choroid plexus papilloma (APP) or metastatic choroid plexus papilloma (CPP); craniospinal fields for metastatic CPC/APP and non-responsive CPC. High risk was defined as choroid plexus carcinoma (CPC), incompletely resected APP, and all metastatic CPT. From 2000 until 2010, 158 CPT patients from 23 countries were enrolled. Results: For randomized CPC, the 5/10 year progression free survival (PFS) of patients on CarbEV (n = 20) were 62%/47%, respectively, compared to 27%/18%, on CycEV (n = 15), (intention-to-treat, HR 2.6, p = 0.032). Within the registry, histological grading was the most influential prognostic factor: for CPP (n = 55) the 5/10 year overall survival (OS) and the event free survival (EFS) probabilities were 100%/97% and 92%/92%, respectively; for APP (n = 49) 96%/96% and 76%/76%, respectively; and for CPC (n = 54) 65%/51% and 41%/39%, respectively. Without irradiation, 12 out of 33 patients with CPC younger than three years were alive for a median of 8.52 years. Extent of surgery and metastases were not independent prognosticators. Conclusions: Chemotherapy for Choroid Plexus Carcinoma is feasible and effective. CarbEV is superior to CycEV. A subset of CPC can be cured without irradiation. [ABSTRACT FROM AUTHOR]

Purpose: Survival in recurrent ependymoma (EPN) depends mainly on the extent of resection achieved. When complete resection is not feasible, chemotherapy is often used to extend progression-free and overall survival. However, no consistent effect of chemotherapy on survival has been found in patients with recurrent EPN. Methods: Systemic chemotherapeutic treatment of 138 patients enrolled in the German HIT-REZ-studies was analyzed. Survival depending on the use of chemotherapy, disease-stabilization rates (RR), duration of response (DOR) and time to progression (TTP) were estimated. Results: Median age at first recurrence was 7.6 years (IQR: 4.0–13.6). At first recurrence, median PFS and OS were 15.3 (CI 13.3–20.0) and 36.9 months (CI 29.7–53.4), respectively. The Hazard Ratio for the use of chemotherapy in local recurrences in a time-dependent Cox-regression analysis was 0.99 (CI 0.74–1.33). Evaluable responses for 140 applied chemotherapies were analyzed, of which sirolimus showed the best RR (50%) and longest median TTP [11.51 (CI 3.98; 14.0) months] in nine patients, with the strongest impact found when sirolimus was used as a monotherapy. Seven patients with progression-free survival > 12 months after subtotal/no-resection facilitated by chemotherapy were found. No definitive survival advantage for any drug in a specific molecularly defined EPN type was found. Conclusion: No survival advantage for the general use of chemotherapy in recurrent EPN was found. In cases with incomplete resection, chemotherapy was able to extend survival in individual cases. Sirolimus showed the best RR, DOR and TTP out of all drugs analyzed and may warrant further investigation. [ABSTRACT FROM AUTHOR]

Pediatric ependymomas comprise biologically distinct tumor entities with different (epi)genetics, age distribution and localization, as well as a different prognosis. Regarding risk stratification within these biologically defined entities, histopathological features still seem to be relevant. The mainstay of treatment is gross total resection (GTR) if possible, achieved with intraoperative monitoring and neuronavigation—and if necessary second surgery—followed by adjuvant radiation therapy. However, there is growing evidence that some ependymal tumors may be cured by surgery alone, while others relapse despite adjuvant treatment. To date, the role of chemotherapy is not clear. Current therapy achieves reasonable survival rates for the majority of ependymoma patients. The next challenge is to go beyond initial tumor control and use risk-adapted therapy to reduce secondary effect and therapy-induced morbidity for low-risk patients and to intensify treatment for high-risk patients. With identification of specific alterations, targeted therapy may represent an option for individualized treatment modalities in the future. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study is to evaluate treatment-related acute and late eye toxicity associated with radiation therapy in childhood and adolescence as correlated with RT (radiotherapy) doses. Methods: From 2001 to 2016, a total of 1725 children and adolescents undergoing radiation therapy were prospectively documented in the Registry of the Evaluation of Side Effects after Radiotherapy in Childhood and Adolescence (RiSK). The RTOG/EORTC criteria were used to classify ocular acute and late effects. Uni- and multivariate analyses were carried out to evaluate the impact of patient age, pre-existing impairments, and radiation dose on ocular toxicity. Results: Of all documented patients, 593 received dose to the eye and formed the basis of this analysis. In 435 patients, information on acute reaction was available and graded 1, 2, 3, and 4 in 49, 17, 0, and 2 patients, respectively. Information on late toxicity was available in 268 patients and graded 1, 2, 3, and 4 in 15, 11, 11, and 5 patients, respectively. The acute toxicity rate was significantly higher in children who received a maximum dose > 50 Gy to the eye (p < 0.001) and who had a pre-existing eye impairment (p < 0.001 in multivariate analysis). The development of late toxicity was significantly higher for patients experiencing acute toxicity and having received a radiation dose > 50 Gy. Conclusion: Acute and late toxicity both correlate with high radiation dose to the eye (> 50 Gy) and acute toxicity additionally with pre-existing eye impairments. [ABSTRACT FROM AUTHOR]

Purpose: Neuroblastoma (NB) is the most common extracranial solid malignancy during childhood. Despite a multimodal treatment approach, the prognosis of patients with metastatic NB is not satisfactory. Although radiotherapy (RT) has become an integral part of treatment of the primary tumor, the role of RT in osteomedullary lesions is not well defined. A retrospective analysis was conducted to evaluate the impact of RT for metastatic sites in children with high-risk NB. Methods: All patients with stage 4 NB from the prospective, multicenter NB trials NB97 and NB2004 who received RT to metastatic sites during frontline treatment were included in this retrospective analysis. Results: A total of 18 children were irradiated with a median dose of 36 Gray (Gy; range 20–45 Gy) to one or more (range 1–3) osteomedullary metastases with or without concomitant RT to the primary tumor site. The median follow-up time was 149 months (range 55–220) in survivors. At 5 years, local relapse-free survival (LRFS) at irradiated metastatic sites and metastases-free survival (MFS) at distant, non-irradiated site rates were 51.4 and 39.9%, respectively. The estimated overall survival (OS) rate at 5 years was 49.4%. No high-grade acute or late toxicity and no secondary malignancy was reported. Conclusion: RT to metastases is feasible for patients with stage 4 NB. However, an impact of RT to residual metastatic sites on outcome was not found. Studies with larger cohorts or prospective trials would be desirable in order to elucidate the role of RT for metastases. [ABSTRACT FROM AUTHOR]

The nat C(p,x) 11 C reaction has been discussed in detail in the past [EXFOR database, Otuka et al. (Nuclear Data Sheets 120:272–276, 2014)]. However, measured activation cross sections by independent experiments are up to 15% apart. The aim of this study is to investigate underlying reasons for these observed discrepancies between different experiments and to determine a new consensus reference cross section at 100 MeV. Therefore, the experimental methods described in the two recent publications [Horst et al. (Phys Med Biol https://doi.org/10.1088/1361-6560/ab4511, 2019) and Bäcker et al. (Nuclear Instrum Methods Phys Res B 454:50–55, 2019)] are compared in detail and all experimental parameters are investigated for their impact on the results. For this purpose, a series of new experiments is performed. With the results of the experiments a new reference cross section of (68±3) mb is derived at (97±3) MeV proton energy. This value combined with the reliably measured excitation function could provide accurate cross section values for the energy region of proton therapy. Because of the well-known gamma-ray spectrometer used and the well-defined beam characteristics of the treatment machine at the proton therapy center, the experimental uncertainties on the absolute cross section could be reduced to 3%. Additionally, this setup is compared to the in-beam measurement setup from the second study presented in the literature (Horst et al. 2019). Another independent validation of the measurements is performed with a PET scanner. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to determine local diagnostic reference levels (LDRLs) of intra-arterial chemotherapy (IAC) procedures of pediatric patients with retinoblastoma (RB) to provide data for establishing diagnostic reference levels (DRLs) in pediatric interventional radiology (IR). Methods: In a retrospective study design, LDRLs and achievable dose (AD) were assessed for children undergoing superselective IAC for RB treatment. All procedures were performed at the flat-panel angiography systems (I) ArtisQ biplane (Siemens Healthineers) and (II) Allura Xper (Philips Healthcare). Patients were differentiated according to age (A1: 1–3 months; A2: 4–12 months; A3: 13–72 months; A4: 73 months–10 years; A5: > 10 years), sex, conducted or not-conducted chemotherapy. Results: 248 neurointerventional procedures of 130 pediatric patients (median age 14.5 months, range 5–127 months) with RB (68 unilateral, 62 bilateral) could be included between January 2010 and March 2020. The following diagnostic reference values, AD, and mean values could be determined: (A2) DRL 3.9 Gy cm2, AD 2.9 Gy cm2, mean 3.5 Gy cm2; (A3) DRL 7.0 Gy cm2, AD 4.3 Gy cm2, mean 6.0 Gy cm2; (A4) DRL 14.5 Gy cm2, AD 10.7 Gy cm2, mean 10.8 Gy cm2; (A5) AD 8.8 Gy cm2, mean 8.8 Gy cm2. Kruskal-Wallis-test confirmed a significant dose difference between the examined age groups (A2–A5) (p < 0.001). There was no statistical difference considering sex (p = 0.076) and conducted or not-conducted chemotherapy (p = 0.627). A successful procedure was achieved in 207/248 cases. Conclusion: We report on radiation exposure during superselective IAC of a pediatric cohort at the German Retinoblastoma Referral Centre. Although an IAC formally represents a therapeutic procedure, our results confirm that radiation exposure lies within the exposure of a diagnostic interventional procedure. DRLs for superselective IAC are substantially lower compared with DRLs of more complex endovascular interventions. [ABSTRACT FROM AUTHOR]

Copyright of Der Radiologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Ependymomas represent about 10% of CNS tumors in children. The proportion of cases defined as anaplastic is about 25%. Prognosis depends on extent of resection, and postoperative radiotherapy, the overall survival rate is 30-60%. Further investigations should clarify the impact of chemotherapy, histological grading, dose, and volume of radiotherapy.Material and Method: Based on historical reports, the recent literature, present guidelines, and ongoing trials an overview is provided for the management of ependymomas in childhood.Results: Local tumor control is the most important aim. Recurrences occur predominantly at the primary tumor region. The main instrument is surgery to effect maximal tumor resection. The addition of radiotherapy could improve survival significantly from 10% to 50%. Regarding the volume of irradiation there is confidence today that local fields are sufficient for all non-disseminated ependymomas. Local dose escalation has been introduced using hyperfractionated schedules. In recent studies this has been shown to increase local control up to 70%. Regarding chemotherapy in ependymomas trials have shown limited efficacy to date. For metastatic disease standard treatment has shown to be insufficient and high dose chemotherapy regimens to increase survival are in study. In younger children radiotherapy should be delayed using early chemotherapy. With pre-irradiation chemotherapy survival rates of 63.3% for children under age of 3 were achieved.Conclusions: At present the cooperating clinicians are optimizing treatment procedures to improve results and to reduce toxicity. In radiotherapy reduction of target volume to the involved field for all non-disseminated ependymomas as well as the introduction of hyperfractionated schedules and conformal therapy with dose escalation are important developments. [ABSTRACT FROM AUTHOR]

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article examines the issues concerning the Register for the evaluation of late side effects after radiation in childhood and adolescence (RiSK) in Germany. Methodology-wise, documentation forms have been collected in the study centre with information about dose-volume histograms that are to be characterized for lungs, heart and kidneys. Based on the results, the researchers concluded that the samples for prospective documentation and toxicity evaluation show the effectiveness of RiSk.