Endocrine Deficiency As a Function of Radiation Dose to the Hypothalamus and Pituitary in Pediatric and Young Adult Patients With Brain Tumors.

PURPOSE: There are sparse data defining the dose response of radiation therapy (RT) to the hypothalamus and pituitary in pediatric and young adult patients with brain tumors. We examined the correlation between RT dose to these structures and development of endocrine dysfunction in this population. MATERIALS AND METHODS: Dosimetric and clinical data were collected from children and young adults (< 26 years of age) with brain tumors treated with proton RT on three prospective studies (2003 to 2016). Deficiencies of growth hormone (GH), thyroid hormone, adrenocorticotropic hormone, and gonadotropins were determined clinically and serologically. Incidence of deficiency was estimated using the Kaplan-Meier method. Multivariate models were constructed accounting for radiation dose and age. RESULTS: Of 222 patients in the study, 189 were evaluable by actuarial analysis, with a median follow-up of 4.4 years (range, 0.1 to 13.3 years), with 31 patients (14%) excluded from actuarial analysis for having baseline hormone deficiency and two patients (0.9%) because of lack of follow-up. One hundred thirty patients (68.8%) with medulloblastoma were treated with craniospinal irradiation (CSI) and boost; most of the remaining patients (n = 56) received involved field RT, most commonly for ependymoma (13.8%; n = 26) and low-grade glioma (7.4%; n = 14). The 4-year actuarial rate of any hormone deficiency, growth hormone, thyroid hormone, adrenocorticotropic hormone, and gonadotropin deficiencies were 48.8%, 37.4%, 20.5%, 6.9%, and 4.1%, respectively. Age at start of RT, time interval since treatment, and median dose to the combined hypothalamus and pituitary were correlated with increased incidence of deficiency. CONCLUSION: Median hypothalamic and pituitary radiation dose, younger age, and longer follow-up time were associated with increased rates of endocrinopathy in children and young adults treated with radiotherapy for brain tumors.

Monte Carlo simulations of ³He ion physical characteristics in a water phantom and evaluation of radiobiological effectiveness.

PURPOSE: (3)He ions may hold great potential for clinical therapy because of both their physical and biological properties. In this study, the authors investigated the physical properties, i.e., the depth-dose curves from primary and secondary particles, and the energy distributions of helium ((3)He) ions. A relative biological effectiveness (RBE) model was applied to assess the biological effectiveness on survival of multiple cell lines. METHODS: In light of the lack of experimental measurements and cross sections, the authors used Monte Carlo methods to study the energy deposition of (3)He ions. The transport of (3)He ions in water was simulated by using three Monte Carlo codes-FLUKA, GEANT4, and MCNPX-for incident beams with Gaussian energy distributions with average energies of 527 and 699 MeV and a full width at half maximum of 3.3 MeV in both cases. The RBE of each was evaluated by using the repair-misrepair-fixation model. In all of the simulations with each of the three Monte Carlo codes, the same geometry and primary beam parameters were used. RESULTS: Energy deposition as a function of depth and energy spectra with high resolution was calculated on the central axis of the beam. Secondary proton dose from the primary (3)He beams was predicted quite differently by the three Monte Carlo systems. The predictions differed by as much as a factor of 2. Microdosimetric parameters such as dose mean lineal energy (y(D)), frequency mean lineal energy (y(F)), and frequency mean specific energy (z(F)) were used to characterize the radiation beam quality at four depths of the Bragg curve. Calculated RBE values were close to 1 at the entrance, reached on average 1.8 and 1.6 for prostate and head and neck cancer cell lines at the Bragg peak for both energies, but showed some variations between the different Monte Carlo codes. CONCLUSIONS: Although the Monte Carlo codes provided different results in energy deposition and especially in secondary particle production (most of the differences between the three codes were observed close to the Bragg peak, where the energy spectrum broadens), the results in terms of RBE were generally similar.

Whole abdominopelvic intensity-modulated radiation therapy for desmoplastic small round cell tumor after surgery.

PURPOSE: Desmoplastic small round cell tumor (DSCRT) is an uncommon pediatric tumor with a poor prognosis. Aggressive multimodality therapy is the current treatment approach; however. treatment toxicity is of concern. We report our results with whole abdominopelvic intensity-modulated radiation therapy (WAP-IMRT) as a component of multimodality therapy for DSCRT at a single institution. MATERIALS/METHODS: Medical records of all patients with DSCRT who received WAP-IMRT as part of definitive treatment at MD Anderson (2006-2010) were identified and reviewed. RESULTS: Eight patients with DSRCT received WAP-IMRT with a median follow-up of 15.2 months. All patients received multiple courses of chemotherapy followed by surgical debulking of intra-abdominal disease; seven also had intraoperative hyperthermic cisplatin. WAP-IMRT was delivered to a total dose of 30 Gy postoperatively; four patients received a simultaneous boost (6-10 Gy) to sites of gross residual disease. Seven patients received concurrent chemotherapy during WAP-IMRT. No Radiation Therapy Oncology Group Grade 4 nausea, vomiting, or diarrhea occurred during RT. Red-cell transfusions were given to two patients to maintain hemoglobin levels >10 g/dL. Grade 4 cytopenia requiring growth factor support occurred in only one patient; no other significant cytopenias were noted. WAP-IMRT resulted in 25% lower radiation doses to the lumbosacral vertebral bodies and pelvic bones than conventional RT plans. The median time to local or distant failure after WAP-IMRT was 8.73 months in seven patients. One patient who had completed RT 20 months before the last follow-up remains alive without evidence of disease. Five patients (63%) experienced treatment failure in the abdomen. Distant failure occurred in three patients (37.5%). CONCLUSIONS: WAP-IMRT with concurrent radiosensitizing chemotherapy was well tolerated after aggressive surgery for DSCRT. Enhanced bone sparing with IMRT probably accounts for the low hematologic toxicity (vs. conventional WAP-RT). This modality should be considered as an additional local-regional control option for DSRCT.