Gliosarcoma (GS) is a malignant, uncommon variant of high-grade glioma comprised of infiltrative glial and atypical sarcomatous cells, identified in adult and pediatric populations. GS has been ...subcategorized into primary (
) and secondary tumors, with the latter typically arising in the setting of prior glioblastoma. Due to its rarity, the pathogenesis, epidemiology and optimal therapy of GS have been based on small retrospective cohort studies, with treatment presently utilizing regimens established for other high-grade gliomas, including combination of resection, radiotherapy and temozolomide-based chemotherapy. As more information is gathered about GS molecular profiles, novel treatment strategies may be developed to improve outcomes of GS patients. Here we summarize results of GS management with focus on the temozolomide era.
Zebrafish (Danio rerio) embryos provide a unique vertebrate model to screen therapeutic agents easily and rapidly because of their relatively close genetic relationship to humans, ready abundance and ...accessibility, short embryonal development, and optical clarity. To validate zebrafish embryos as a screen for radiation modifiers, we evaluated the effects of ionizing radiation in combination with a known radioprotector (free radical scavenger Amifostine) or radiosensitizing agent (tyrosine kinase inhibitor AG1478).
Viable zebrafish embryos were exposed to 0-10 Gy single-fraction 250 kVp X-rays with or without either Amifostine (0-4 mM) or AG1478 (0-10 microM) at defined developmental stages from 1-24 h postfertilization (hpf). Embryos were examined for morphologic abnormalities and viability until 144 hpf.
Radiation alone produced a time- and dose-dependent perturbation of normal embryonic development and survival with maximal sensitivity at doses > or =4 Gy delivered before 4 hpf. Amifostine markedly attenuated this effect, whereas AG1478 enhanced teratogenicity and lethality, particularly at therapeutically relevant (2-6 Gy) radiation doses.
Collectively, these data validate the use of zebrafish as a vertebrate model to assess the effect of radiation alone or with radiation response modulators. Zebrafish embryos may thus provide a rapid, facile system to screen novel agents ultimately intended for human use in the context of therapeutic or accidental radiation exposure.
In most childhood head and neck cancers, radiotherapy is an essential component of treatment; however, it can be associated with problematic long-term complications. Proton beam therapy is accepted ...as a preferred radiation modality in pediatric cancers to minimize the late radiation side effects. Given that childhood cancers are a rare and heterogeneous disease, the support for proton therapy comes from risk modeling and a limited number of cohort series. Here, we discuss the role of proton radiotherapy in pediatric head and neck cancers with a focus on reducing radiation toxicities. First, we compare the efficacy and expected toxicities in proton and photon radiotherapy for childhood cancers. Second, we review the benefit of proton radiotherapy in reducing acute and late radiation toxicities, including risks for secondary cancers, craniofacial development, vision, and cognition. Finally, we review the cost effectiveness for proton radiotherapy in pediatric head and neck cancers. This review highlights the benefits of particle radiotherapy for pediatric head and neck cancers to improve the quality of life in cancer survivors, to reduce radiation morbidities, and to maximize efficient health care use.
Abstract Purpose Volumetric modulated arc therapy (VMAT) has been shown by multiple planning studies to hold dosimetric advantages over intensity modulated radiation therapy (IMRT) in the management ...of brain tumors, including glioblastoma (GBM). Although promising, the clinical impact of these findings has not been fully elucidated. Methods and Materials We retrospectively reviewed consecutive patients with a pathologic-confirmed diagnosis of GBM who were treated between 2014 and 2015, a period that encompassed the transition from IMRT to VMAT at a single institution. After surgery, radiation with VMAT consisted of 2 to 3 coplanar arcs with or without an additional noncoplanar arc or IMRT with 5 to 6 gantry angles with concurrent and adjuvant temozolomide. Actuarial analyses were performed using the Kaplan Meier method. Results A total of 88 patients treated with IMRT (n = 45) and VMAT (n = 43) were identified. Patients were similar in terms of age, sex, performance status, extent of resection, and the high dose target volume. At a median follow-up time of 27 months (range, .7-32.3 months), the overall survival, freedom from progression, and freedom from new or worsening toxicity rates were not different between the 2 treatment groups (log-rank: P = .33; .87; and .23, respectively). There was no difference in incidences of alopecia, erythema, nausea, worsening or new onset fatigue, or headache during radiation, or temozolomide dose reduction for thrombocytopenia or neutropenia (all P > .05). Patterns of failure were different with more out of field failures in the IMRT group ( P = .02). The mean time of treatment (TOT) was significantly reduced by 29% ( P < .01) with VMAT (mean TOT: 10.3 minutes) compared with IMRT (mean TOT: 14.6 minutes). Conclusions For GBM, treatment with VMAT results in similar oncologic and toxicity outcomes compared with IMRT and may improve resource utilization by reducing TOT. VMAT should be considered a potential radiation modality for patients with GBM.
Patient travel time can cause treatment delays when providers and families decide to seek proton therapy. We examined whether travel distance or referral pattern (domestic versus international) ...affects time to radiation therapy and subsequent disease outcomes in patients with medulloblastoma at a large academic proton center.
Children with medulloblastoma treated at MD Anderson (MDA) with a protocol of proton beam therapy (PBT) between January 4, 2007, and June 25, 2014, were included in the analysis. The Wilcoxon rank-sum test was used to study the association between time to start of radiation and distance. Classification- and regression-tree analyses were used to explore binary thresholds for continuous covariates (ie, distance). Failure-free survival was defined as the time interval between end of radiation and failure or death.
96 patients were included in the analysis: 17 were international (18%); 19 (20%) were from Houston, Texas; 21 were from other cities inside Texas (21%); and 39 (41%) were from other US states. The median time from surgery to start of radiation was not significantly different for international patients (median = 1.45 months) compared with US patients (median = 1.15 months;
= .13). However, time from surgery to start of radiation was significantly longer for patients residing > 1716 km (> 1066 miles) from MDA (median = 1.31 months) than for patients residing ≤ 1716 km (≤ 1066 miles) from MDA (median = 1.05 months;
= .01). This 1- to 2-week delay (median = 7.8 days) did not affect failure-free survival (hazard ratio = 1.34;
= .43).
We found that short delays in proton access can exist for patients traveling long distances to proton centers. However, in this study, treatment delays did not affect outcomes. This highlights the appropriateness of PBT in the face of travel coordination. Investment by proton centers in a rigorous intake process is justified to offer timely access to curative PBT.
Spinal stereotactic body radiation therapy (SBRT) continues to emerge as an effective therapeutic approach to spinal metastases; however, treatment planning and delivery remain resource intensive at ...many centers, which may hamper efficient implementation in clinical practice. We sought to develop a generalizable class solution approach for spinal SBRT treatment planning that would allow confidence that a given plan provides optimal target coverage, reduce integral dose, and maximize planning efficiency.
We examined 91 patients treated with spinal SBRT at our institution. Treatment plans were categorized by lesion location, clinical target volume (CTV) configuration, and dose fractionation scheme, and then analyzed to determine the technically achievable dose gradient. A radial cord expansion was subtracted from the CTV to yield a planning CTV (pCTV) construct for plan evaluation. We reviewed the treatment plans with respect to target coverage, dose gradient, integral dose, conformality, and maximum cord dose to select the best plans and develop a set of class solutions.
The class solution technique generated plans that maintained target coverage and improved conformality (1.2-fold increase in the 95% van't Riet Conformation Number describing the conformality of a reference dose to the target) while reducing normal tissue integral dose (1.3-fold decrease in the volume receiving 4 Gy (V(4Gy)) and machine output (19% monitor unit (MU) reduction). In trials of planning efficiency, the class solution technique reduced treatment planning time by 30% to 60% and MUs required by ∼20%: an effect independent of prior planning experience.
We have developed a set of class solutions for spinal SBRT that incorporate a pCTV metric for plan evaluation while yielding dosimetrically superior treatment plans with increased planning efficiency. Our technique thus allows for efficient, reproducible, and high-quality spinal SBRT treatment planning.
The Pediatric Normal Tissue Effects in the Clinic (PENTEC) pulmonary task force reviewed dosimetric and clinical factors associated with radiation therapy (RT)-associated pulmonary toxicity in ...children.
Comprehensive search of PubMed (1965-2020) was conducted to assess available evidence and predictive models of RT-induced lung injury in pediatric cancer patients (<21 years old). Lung dose for radiation pneumonitis (RP) was obtained from dose-volume histogram (DVH) data. RP grade was obtained from standard criteria. Clinical pulmonary outcomes were evaluated using pulmonary function tests (PFTs), clinical assessment, and questionnaires.
More than 2,400 abstracts were identified; 460 articles had detailed treatment and toxicity data; and 11 articles with both detailed DVH and toxicity data were formally reviewed. Pooled cohorts treated during 1999 to 2016 included 277 and 507 patients age 0.04 to 22.7 years who were evaluable for acute and late RP analysis, respectively. After partial lung RT, there were 0.4% acute and 2.8% late grade 2, 0.4% acute and 0.8% late grade 3, and no grade 4 to 5 RP. RP risk after partial thoracic RT with mean lung dose (MLD) <14 Gy and total lung V
<30% is low. Clinical and self-reported pulmonary outcomes data included 8,628 patients treated during 1970 to 2013, age 0 to 21.9 years. At a median 2.9- to 21.9-year follow-up, patients were often asymptomatic; abnormal PFTs were common and severity correlated with lung dose. At ≥10-year follow-up, multi-institutional studies suggested associations between total or ipsilateral lung doses >10 Gy and pulmonary complications and deaths. After whole lung irradiation (WLI), pulmonary toxicity is higher; no dose response relationship was identified. Bleomycin and other chemotherapeutics at current dose regimens do not contribute substantially to adverse pulmonary outcomes after partial lung irradiation but increase risk with WLI.
After partial lung RT, acute pulmonary toxicity is uncommon; grade 2 to 3 RP incidences are <1%. Late toxicities, including subclinical/asymptomatic impaired pulmonary function, are more common (<4%). Incidence and severity appear to increase over time. Upon review of available literature, there appears to be low risk of pulmonary complications in children with MLD < 14 Gy and V
<30% using standard fractionated RT to partial lung volumes. A lack of robust data limit guidance on lung dose/volume constraints, highlighting the need for additional work to define factors associated with RT-induced lung injury.
The purpose of this study was to assess what factors influence radiation therapy (RT) utilization in patients with glioblastoma and to ascertain how patterns of care have changed over time.
A total ...of 9103 patients with supratentorial glioblastoma in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2006 were analyzed. Demographic information was obtained, including age, sex, race, year of diagnosis, and marital status. Treatment characteristics included receipt of RT and surgical resection.
In total, 76.8% of patients received RT, whereas 78% received resection. Patients of male sex, who were currently married, who were <65 years old, and who underwent resection were more likely to receive RT. The average annual percentage change in RT utilization in the years 1990-2006 was -0.41% (95% confidence interval CI, -0.23 to -0.58), whereas for resection it was 0.26% (95% CI, 0.03 to 0.50). This equates to a 6.5% decrease in RT utilization and a 4.2% increase in resection during this time period. Patients treated with RT had a 2-year overall survival of 11.4%, compared with 5.2% in those not treated with RT (P < .00001). Multivariate analysis showed that younger age (continuous; odds ratio OR, 0.97; P < .0001), marital status (OR, 1.62; P < .0001), surgical resection (OR, 1.72; P < .0001), and year of diagnosis 1998-2006 compared with 1990-1997 (OR, 0.82; P < .0001) were associated with RT utilization, whereas sex, lesion size, and race were not.
SEER data show a decreasing utilization of RT in patients with glioblastoma from 1990 to 2006. Patients who were older, who were unmarried, and who underwent biopsy only were less likely to receive RT.
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