Aidnag Z. Diaz

Phase I three-dimensional conformal radiation dose escalation study in newly diagnosed glioblastoma: Radiation Therapy Oncology Group Trial 98-03.

PURPOSE To evaluate in a Phase I trial the feasibility and toxicity of dose-escalated three-dimensional conformal radiotherapy (3D-CRT) concurrent with chemotherapy in patients with primary supratentorial glioblastoma (GBM). METHODS AND MATERIALS A total of 209 patients were enrolled. All received 46 Gy in 2-Gy fractions to the first planning target volume (PTV(1)), defined as the gross tumor volume (GTV) plus 1.8 cm. A subsequent boost was given to PTV(2), defined as GTV plus 0.3 cm. Patients were stratified into two groups (Group 1: PTV(2) <75 cm(3); Group 2: PTV(2) >or=75 cm(3)). Four RT dose levels were evaluated: 66, 72, 78, and 84 Gy. Carmustine 80 mg/m(2) was given during RT, then every 8 weeks for 6 cycles. Pretreatment characteristics were well balanced. RESULTS Acute and late Grade 3/4 RT-related toxicities were no more frequent at higher RT dose or with larger tumors. There were no dose-limiting toxicities (acute Grade >or=3 irreversible central nervous system toxicities) observed on any dose level in either group. On the basis of the absence of dose-limiting toxicities, dose was escalated to 84 Gy in both groups. Late RT necrosis was noted at 66 Gy (1 patient), 72 Gy (2 patients), 78 Gy (2 patients), and 84 Gy (3 patients) in Group 1. In Group 2, late RT necrosis was noted at 78 Gy (1 patient) and 84 Gy (2 patients). Median time to RT necrosis was 8.8 months (range, 5.1-12.5 months). Median survival in Group 1 was 11.6-19.3 months. Median survival in Group 2 was 8.2-13.9 months. CONCLUSIONS Our study shows the feasibility of delivering higher than standard (60 Gy) RT dose with concurrent chemotherapy for primary GBM, with an acceptable risk of late central nervous system toxicity.

Sparing of the hippocampus, limbic circuit and neural stem cell compartment during partial brain radiotherapy for glioma: A dosimetric feasibility study

Introduction: The aim of this study was to assess the feasibility of sparing contralateral or bilateral neural stem cell (NSC) compartment, hippocampus and limbic circuit during partial brain radiotherapy (PBRT).

Patterns-of-failure after helical tomotherapy-based chemoradiotherapy for head and neck cancer: implications for CTV margin, elective nodal dose and bilateral parotid sparing.

OBJECTIVES There is debate about the optimal clinical target volume (CTV) expansion and prophylactic nodal dose (PND) in head and neck IMRT. We evaluated our patterns-of-failure (POF) after helical tomotherapy-based concurrent chemoradiotherapy (CCRT) to assess the oncologic safety of reducing the CTV, PND, and bilateral parotid sparing (BPS). MATERIALS AND METHODS All patients with locally advanced squamous cell carcinoma of the head and neck treated with curative intent CCRT between January 2007 and April 2013 at a single institution were included in this retrospective study. Locoregional recurrences (LRR) were overlaid on the treatment plan, and POF was determined relative to planned dose. RESULTS One hundred and fourteen patients treated with CCRT were evaluated, 74% of whom underwent BPS. The median follow-up for surviving patients was 29.3 months. The 3-year cumulative incidence of locoregional failure, distant metastasis, progression-free and overall survival were 20%, 20%, 56% and 73% respectively. The local failures (n = 12) were either entirely contained within or centered on the original gross tumor volume (GTV), and all but 2 regional recurrences were in GTV. There were no nodal failures in the low-dose or peri-parotid neck (including ipsilateral neck). DISCUSSION Nearly all LRR were located within the GTV suggesting that minimal-to-zero margin is required for CTV 70. The nodal recurrence pattern suggests the safety of routine bilateral parotid sparing and relatively low biologically equivalent dose (54 Gy in 33fx) to the low-risk neck.

Current Status of Immunotherapy and Gene Therapy for High-Grade Gliomas

BACKGROUND Despite improvements in surgical technique, radiation therapy delivery, and options for systemic cytotoxic therapy, the median survival for patients with newly diagnosed glioblastoma multiforme remains poor at 15 months with trimodality therapy. Multiple immunologic approaches are being tested to enhance the response of these tumors to existing therapy and/or to stimulate innate immune responses. METHODS We review the existing data that support the continued development of immunologic therapy in the treatment armamentarium against glioblastoma multiforme, with a focus on clinical data documenting outcomes. RESULTS In phase I and phase II trials, antitumor vaccines (dendritic and formalin-fixed) have demonstrated clinical efficacy with mild toxicity, suggesting that innate immune responses can be amplified and directed against these tumors. Suicide gene therapy (gene-mediated cytotoxic therapy) using a number of viral vectors and molecular pathways has also shown efficacy in completed phase I and ongoing phase II trials. In addition, neural stem cells are being investigated as vectors in this approach. CONCLUSIONS Although phase III data are needed before immunologic therapies can be widely implemented into clinical practice, the existing phase I and phase II data suggest that these therapies can produce meaningful and sometimes durable responses in patients with glioblastoma multiforme with mild toxicity compared with other existing therapies.

Dosimetric characteristics of the small diameter BrainLab™ cones used for stereotactic radiosurgery

The purpose was to study the dosimetric characteristics of the small diameter (≤10.0 mm) BrainLAB cones used for stereotactic radiosurgery (SRS) treatments in conjunction with a Varian Trilogy accelerator. Required accuracy and precision in dose delivery during SRS can be achieved only when the geometric and dosimetric characteristics of the small radiation fields is completely understood. Although a number of investigators have published the dosimetric characteristics of SRS cones, to our knowledge, there is no generally accepted value for the relative output factor (ROF) for the 5.0 mm diameter cone. Therefore, we have investigated the dosimetric properties of the small (≤10.0 mm) diameter BrainLAB SRS cones used in conjunction with the iPlan TPS and a Trilogy linear accelerator with a SRS beam mode. Percentage depth dose (PDD), off‐axis ratios (OAR), and ROF were measured using a SRS diode and verified with Monte Carlo (MC) simulations. The dependence of ROF on detector material response was studied. The dependence of PDD, OAR, and ROF on the alignment of the beam CAX with the detector motion line was also investigated using MC simulations. An agreement of 1% and 1 mm was observed between measurements and MC for PDD and OAR. The calculated ROF for the 5.0 mm diameter cone was 0.692±0.008 — in good agreement with the measured value of 0.683±0.007 after the diode response was corrected. Simulations of the misalignment between the beam axis and detector motion axis for angles between 0.5°–1.0° have shown a deviation > 2% in PDD beyond a certain depth. We have also provided a full set of dosimetric data for BrainLAB SRS cones. Monte Carlo calculated ROF values for cones with diameters less than 10.0 mm agrees with measured values to within 1.8%. Care should be exercised when measuring PDD and OAR for small cones. We recommend the use of MC to confirm the measurement under these conditions. PACS numbers: 87.53.Ly, 87.55.‐x, 87.53.Bn, 87.55.K‐

Integral dose delivered to normal brain with conventional intensity-modulated radiotherapy (IMRT) and helical tomotherapy IMRT during partial brain radiotherapy for high-grade gliomas with and without selective sparing of the hippocampus, limbic circuit and neural stem cell compartment

We compared integral dose with uninvolved brain (IDbrain) during partial brain radiotherapy (PBRT) for high‐grade glioma patients using helical tomotherapy (HT) and seven field traditional inverse‐planned intensity‐modulated radiotherapy (IMRT) with and without selective sparing (SPA) of contralateral hippocampus, neural stem cell compartment (NSC) and limbic circuit.

Integral dose delivered to normal brain with conventional intensity‐modulated radiotherapy (IMRT) and helical tomotherapy IMRT during partial brain radiotherapy for high‐grade gliomas with and without selective sparing of the hippocampus, limbic circuit a

We compared integral dose with uninvolved brain (IDbrain) during partial brain radiotherapy (PBRT) for high‐grade glioma patients using helical tomotherapy (HT) and seven field traditional inverse‐planned intensity‐modulated radiotherapy (IMRT) with and without selective sparing (SPA) of contralateral hippocampus, neural stem cell compartment (NSC) and limbic circuit.

The effect of a limited number of projections and reconstruction algorithms on the image quality of megavoltage digital tomosynthesis.

In order to investigate the effect of the number of projections on digital tomosynthesis image quality, images were acquired over a 40 degree arc and sampled into sets of 2 to 41 projections used as input to three different reconstruction algorithms: the shift‐and‐add, the Feldkamp‐Davis‐Kress filtered back projection algorithms, and the simultaneous algebraic reconstruction technique. The variation of several image characteristics, such as in‐plane resolution, contrast to noise ratio, artifact spread, volumetric accuracy, and dose, are investigated based on the reconstruction algorithms used and also the number of projections used as source data. The results suggest that only 11 projections are required since the various parameters checked do not improve much past that number. As a reconstruction algorithm, SART did best but took much longer to reconstruct images. Thus, if reconstruction time is a determining factor, filtered back‐projection looks like a better compromise. PACS number: 87.57.C‐, 87.57.nf, 87.57.Q‐, 87.59.‐e

High-Grade Glioma Relationship to the Neural Stem Cell Compartment: A Retrospective Review of 104 Cases

PURPOSE To assess the incidence of involvement of the neural stem cell (NSC) compartment by high-grade astrocytomas in a series of adult patients. METHODS AND MATERIALS One hundred four initial diagnostic cranial magnetic resonance imaging series were reviewed. For each series, the gross tumor volume (GTV; enhancing tumor on T(1)), edema (hyperintensity on T(2) FLAIR), and the NSC compartment (hippocampal formation and lateral ventricle plus a 5-mm expansion) were identified. Involvement of NSC by GTV and edema was assessed. For tumors not involving NSC, we measured distances from NSC to GTV and edema. Maximum diameters of GTV were measured for each case. Subset analysis was performed for GTV of ≤ 2 cm and ≤ 3 cm in maximum diameter to assess the incidence of involvement of NSC by this group of smaller tumors. For 10 representative tumors, minimum distances from GTV center to NSC were calculated. RESULTS A total of 103/104 (99.0%) tumors, regardless of GTV maximum diameter, demonstrated involvement of NSC. A total of 101/104 (97.1%) tumors had NSC involvement by GTV, and 2/104 (1.9%) patients showed edema only. For GTV not involving NSC, the mean distance from NSC to GTV was 0.8 cm (range, 0.5--1.4 cm). The mean shortest distance from the center of GTV to NSC was 1.5 cm (range, 0.9--2.6 cm). Involvement of NSC by GTV was 90.9% (10/11 tumors) for GTV of ≤ 2 cm and 95.7% (22/23 tumors) for GTV of ≤ 3 cm. CONCLUSIONS Our results support the hypothesis that the NSC compartment represents the putative site of origin for these tumors. NSC involvement does not appear to represent a volumetric phenomenon.

Distinct histopathologic features of radiation‐induced chronic sinusitis

Chronic rhinosinusitis (CRS) is a commonly observed sequela after radiation therapy to the paranasal sinuses. The histopathologic features of radiation‐induced CRS have yet to be determined and may have major implications in disease management.