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Background: Local control for patients with Ewing sarcoma (EWS) who present with large tumors are suboptimal when treated with standard radiation therapy (RT) doses of 54-55.8 Gy. The purpose of this study is to determine local control and toxicity of dose-escalated RT for tumors =8 cm (greatest diameter at diagnosis) in pediatric and young adult patients with EWS. Methods: Eligible patients =30 years old with newly diagnosed EWS =8 cm treated with definitive conformal or intensity modulated photon, or proton radiation therapy techniques were included. All patients in the study received dose-escalated RT doses. Outcomes included overall survival (OS), event-free survival (EFS), local failure rates, and toxicity. Results: Thirty-two patients were included, 20 patients presented with metastatic disease and 12 patients with localized disease. The median RT dose was 64.8 Gy (range, 59.4-69.4 Gy) with variability of doses to protect normal surrounding tissues. All patients received systemic chemotherapy. The 5-year OS and EFS for the cohort was 64.2% and 42%, respectively. The 5-year cumulative incidence of local failure was 6.6%. There were two combined local and distant failures with no isolated local failures. Twenty-nine patients experienced short term toxicity, 90% of those being radiation dermatitis. Twenty-seven patients experienced long-term toxicity, with only one experiencing grade 4 toxicity, a secondary malignancy after therapy. Conclusion: This study demonstrates that definitive RT for pediatric and young adult patients with EWS =8 cm provides high rates of local control, while maintaining a tolerable toxicity profile. [ABSTRACT FROM AUTHOR]

Simple Summary: This study addresses the challenge of respiratory motion in pediatric patients undergoing proton therapy for total lymphoid irradiation (TLI), an essential component of reduced-intensity conditioning regimens for hematopoietic cell transplant (HCT) patients. The primary concern is the interplay effect, which can cause deviations from the planned dose during respiratory motion. The research utilized static and 4D CT images from ten patients to simulate the interplay effect and assess its impact on treatment planning. The study concludes that 4D plan evaluation and robust optimization techniques can help address respiratory motion challenges in proton TLI treatments, especially in cases where other motion management strategies like breath-holding are not feasible due to the patient's young age, the need for anesthesia, or medical conditions. Patient-specific respiratory motion evaluations are crucial to ensure adequate dosimetric coverage in proton therapy for pediatric patients. (1) Background: The most significant cause of an unacceptable deviation from the planned dose during respiratory motion is the interplay effect. We examined the correlation between the magnitude of splenic motion and its impact on plan quality for total lymphoid irradiation (TLI); (2) Methods: Static and 4D CT images from ten patients were used for interplay effect simulations. Patients' original plans were optimized based on the average CT extracted from the 4D CT and planned with two posterior beams using scenario-based optimization (±3 mm of setup and ±3% of range uncertainty) and gradient matching at the level of mid-spleen. Dynamically accumulated 4D doses (interplay effect dose) were calculated based on the time-dependent delivery sequence of radiation fluence across all phases of the 4D CT. Dose volume parameters for each simulated treatment delivery were evaluated for plan quality; (3) Results: Peak-to-peak splenic motion (≤12 mm) was measured from the 4D CT of ten patients. Interplay effect simulations revealed that the ITV coverage of the spleen remained within the protocol tolerance for splenic motion, ≤8 mm. The D100% coverage for ITV spleen decreased from 95.0% (nominal plan) to 89.3% with 10 mm and 87.2% with 12 mm of splenic motion; (4) Conclusions: 4D plan evaluation and robust optimization may overcome problems associated with respiratory motion in proton TLI treatments. Patient-specific respiratory motion evaluations are essential to confirming adequate dosimetric coverage when proton therapy is utilized. [ABSTRACT FROM AUTHOR]

The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient-specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment-related toxicity and possible targets for intervention in this population. Furthermore, although current long-term follow-up guidelines comprehensively address specific therapy-related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment-related health risk and evolving treatment approaches, a patient-centered and risk-adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133-152. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background/Aims: To evaluate clinical and dosimetric predictors of trigeminal nerve dysfunction (TND) following stereotactic radiosurgery (SRS) for Trigeminal Neuralgia (TN). Methods: We retrospectively reviewed our cohort of 446 patients with TN who underwent SRS between 1999- 2008. Median follow-up was 25.1 and 17.4 months (mo) in those with and without TND respectively. Dosimetric and anatomic measurements and clinical features including Burchiel subtype, pain quality, prior procedures, comorbidities and medications were evaluated for their influence on the TND using univariate and multivariate logistic regression modeling. Results: TND was observed in 44.6% of patients and was similar across facial pain types. Those with TND had prolonged time to pain relapse [(TND, 68.48 mo) vs. (No TND, 29.37 mo)]. Multivariate analysis identified sharp pain at diagnosis (OR 0.594; 95%CI 0.38-0.91), and dorsal root entry zone (DREZ) maximum dose (OR 1.022; 95%CI 1.00-1.04) as predictors of TND. Conclusions: The presence of sharp pain and increasing DREZ maximum dose were independently associated with TND. Patients with atypical facial pain were at lower risk of TND with increasing dose relative to Type 1 and Type 2 TN. [ABSTRACT FROM AUTHOR]

Purpose: We investigate clinical, pathologic and treatment paradigm-related factors affecting local control of brain metastases after stereotactic radiosurgery (SRS) with or without whole brain radiotherapy (WBRT). Methods and materials: Patients with brain metastases treated with SRS alone, before or after WBRT were considered to determine predictors of local failure (LF), time to failure and survival. Results: Among 137 patients, 411 brain metastases were analyzed. 23% of patients received SRS alone, 51% received WBRT prior to SRS and 26% received SRS followed by WBRT. LF occurred in 125 metastases: 63% after SRS alone, 20% after WBRT then SRS and 22% after SRS then WBRT. Median time to local failure was significantly less after SRS alone compared to WBRT then SRS (12.1 v. 22.7 months, p=0.003). Tumor volume was significantly associated with LF (HR:5.2, p<0.001, 95% CI:3.4-7.8). Conclusions: WBRT+SRS results in reduced LF. Local control was not significantly different after SRS as salvage therapy versus upfront SRS. [ABSTRACT FROM AUTHOR]

Background: Stereotactic radiosurgery for the treatment of brain metastases is commonly delivered without regard to primary cancer histology. This study sought to determine if the primary site of origin for brain metastases affected the propensity for local failure. Methods: A total of 83 patients with 200 brain metastases were examined retrospectively for predictors of infield failure. Tumor, patient, and treatment characteristics were analyzed including primary tumor histology, radiosurgical dose and age. Cox proportional hazards models, univariate and multivariate analyses were used to identify predictors of local failure. Results: Freedom from local failure for the entire population was 83% and 65% at 6 and 12 months, respectively. Multivariate analysis revealed that breast cancer brain metastases have a significantly lower risk of local failure than melanoma (HR = 0.31, p< 0.001). Additionally, multivariate analysis revealed that increasing dose lowered risk for local failure (HR = 0.87, p<0.001). Conclusions: Melanoma histology leads to a higher rate of local failure. Higher prescription dose results in higher incidence of local control. [ABSTRACT FROM AUTHOR]

Background: Cavernous sinus metastases represent difficult clinical scenarios because of the lack of surgical options. We investigate the use of Gamma Knife stereotactic radiosurgery (GKRS) as a treatment option of these metastases. Objectives: To determine the patterns of failure for cavernous sinus metastases and to identify factors that predict for improved outcomes. Methods: This is a retrospective review of 19 patients treated with GKRS for cavernous sinus metastases over a 9-year period between May 2002 and October 2011. The median marginal tumor dose was 18 Gy. Patients were followed with serial imaging. Kaplan Meier analysis was used to estimate local control and overall survival. Fischer exact test was used to determine any predictive factors for local control or survival. Results: Median follow-up time was 22.4 months. Kaplan Meier estimate of overall survival at 1, 2, and 4 years was 76%, 44%, and 44% survival, respectively. 11 patients experienced intracranial failure. Of these, 7 (64%) were local and 4 (36%) were distant intracranial failures. Local control was 76%, 44%, and 44% at 1, 2 and 4 years, respectively. Six of seven local failures in the series were considered to be marginal failures because they were abutting the 50% isodose volume. Head and neck primary tumors were associated with 86% of local failures (P = 0.017) and was the only factor that predicted for local failure. Conclusions: GKRS appears to be a feasible and safe modality for treatment of cavernous sinus metastases. Local failures appear to be due to a marginal miss of microscopically occult disease. [ABSTRACT FROM AUTHOR]

Although significant advances have been made in treating malignant pediatric central nervous system tumors such as medulloblastoma, no effective therapy exists for diffuse pontine glioma or intramedullary spinal astrocytoma. Biology of these 2 tumors is poorly understood, in part because diffuse pontine gliomas are not treated surgically, and tumor specimens from intramedullary spinal astrocytomas are rare and minuscule. At the 2007 Neurobiology of Disease in Children Symposium, we presented evidence that malignant glioma behaviors, including antiapoptosis, invasiveness, and treatment resistance, are enhanced by hyaluronan, an extracellular glycosaminoglycan. We review the clinical course of pediatric intramedullary spinal astrocytoma and diffuse pontine glioma, and show expression of membrane proteins that interact with hyaluronan: CD44, extracellular matrix metalloproteinase inducer, and breast cancer resistance protein (BCRP/ABCG2). Furthermore, we describe novel animal models of these tumors for preclinical studies. These findings suggest that hyaluronan antagonism has potential therapeutic value in malignant central nervous system tumors. [ABSTRACT FROM AUTHOR]