The use of 4D CT simulation assists in defining appropriate target margins when treatment of a mobile target is desired. 4D techniques have been applied in the setting of breast cancer, but the benefit of this application remains uncertain. We therefore performed a dosimetric analysis of our institution's experience using 4D CT simulation for patients requiring post-mastectomy chest wall irradiation to determine whether it improves treatment delivery with respect to target coverage, lung dose, and cardiac ventricle dose. The treatment plans of 13 patients who underwent 4D CTs between Jan 1, 2009 and March 16, 2010 were reviewed. For each patient, a standardized chest wall contour was created per RTOG guidelines on both the free breathing CT (FBCT) and an "average respiratory phase" CT (ACT) generated by applying a bellows device around the upper abdomen to track respiration. Patients also received irradiation to regional lymph nodes, but only the chest wall was defined as the target for this study. The cardiac ventricles and ipsilateral lung were contoured on each CT as critical normal structures. A 3D conformal treatment plan using opposed tangential fields (n = 11) or an IMRT plan (n = 2) was created on each FBCT. The FBCT plan was then applied to the corresponding ACT for each patient and specified parameters were measured. The 2 CTs were compared with respect to target volume (cm3), target volume coverage (V95%), mean cardiac ventricle dose for patients with left-sided breast cancer (n = 5), and mean ipsilateral lung dose. A two-tailed paired t-test analysis was used for each parameter. There was no significant difference between the 2 CTs with respect to the analyzed parameters. The mean chest wall target volume was 764.6 cm3 for the FBCTs and 763 cm3 for the ACTs (p = 0.6). The average V95% was 82.9% for the FBCTs compared with 82.8% for the ACTs (p = 0.6). 5 patients had left-sided breast cancer, and the mean cardiac ventricle dose for these patients was 495.78 c Gy for the FBCT group and 495.98 for the ACT group (p = 0.96). Ipsilateral mean lung dose was also studied and there was no significant difference (p = 0.43) between the FBCT group (1394.3 c Gy) and the ACT group (1385.2 c Gy). Our results suggest that 4D CT may not significantly improve the accuracy and predictability of dose delivery to the target volume, ipsilateral lung, or cardiac ventricles in patients with breast cancer requiring post-mastectomy irradiation. While the chest wall does deform during respiration, actual excursion is minimal, and there is minimal change in the shape and size of the target volume. 4D CT is a resource-intensive procedure that requires further study to demonstrate consistent dosimetric benefit if it is to be routinely used in the clinic.

To assess frequency of involvement of neural stem cell compartment (NSC) in a series of low grade (World Health Organization [WHO] grades 1/2) and high grade (WHO grades 3/4) gliomas. Initial and subsequent cranial MRI series for 80 low grade gliomas and 104 high grade gliomas treated between 2000 and 2010 at our institution were reviewed. Maximum diameter of gross disease (GTV) was measured, and involvement of NSC was documented if present. For cases not involving NSC, minimum distance from GTV to NSC and distance from NSC to center of tumor were measured. For low grade gliomas which later recurred as high grade gliomas time interval to progression was measured, and each recurrence was evaluated for involvement of NSC. Low grade tumors were stratified by histology (astrocytoma, oligodendroglioma, oligoastrocytoma, or other), tumor grade (1 vs. 2), MIB-1 proliferative status, and pattern of growth (infiltrative vs. localized). High grade tumors were stratified by histology (for grade 3 tumors: astrocytoma, oligodendroglioma, or oligoastrocytoma) and tumor grade (3 vs. 4). All tumors were stratified by maximum diameter of gross disease (≤2 cm vs. >2 cm, ≤3 cm vs. >3 cm). A total of 71.3% (57/80) of low grade tumors involved NSC at presentation. Infiltrative low grade tumors more often involved NSC than localized tumors (94.6% vs. 51.2%, RR 1.85, CI 1.58-2.12, p = 0.13), as did tumors >2 cm or >3 cm vs. smaller tumors (81.8% vs. 21.4% and 86.5% vs. 42.9%, RR 3.82 and 2.02, CI 3.24-4.4 and 1.71-2.33, p = 0.086 and 0.123, respectively). For low grade tumors, tumor grade did not predict NSC involvement (72.4% grade 2 vs. 68.2% grade 1, RR 1.06, CI 1.04-1.08, p = 0.44), nor did histology or MIB-1 proliferative status. Of the 9 high grade recurrences, all were originally grade 2, 77.8% initially involved NSC, and 88.9% of recurrences involved NSC. Ninety-nine percent (103/104) of high grade tumors involved NSC at presentation, 101/104 (97.1%) by GTV, 2/104 pts (1.9%) by edema only. Histology (for grade 3 tumors), tumor grade, and GTV diameter did not affect the rate of NSC involvement. Involvement of NSC by GTV was 90.9% (10/11) for GTV 2cm or less and 95.7% (22/23) for GTV 3cm or less. Infiltrative low grade gliomas frequently involve NSC at presentation and at time of recurrence as high grade glioma, as do de novo high grade gliomas. While tumor volume may affect the rate of NSC involvement by low grade gliomas, it has no influence on the rate of NSC involvement by high grade gliomas, supporting our hypothesis that high grade gliomas and a subset of high risk low grade gliomas arise from the NSC compartment.

Purpose: Advances in functional imaging may allow identification and targeting of tumor sub-volumes based on their biological characteristics, allowing selective boosting of dose to radio-resistant sub-volumes during treatment planning. The purpose of this study was to redistribute high dose regions toward the PET-hot regions as identified on PET/CT images during High-Dose-Rate (HDR) brachytherapy for cervical cancer while maintaining a clinically acceptable DVH. Material and Methods: FDG-PET and CT images were acquired and registered. The tumor volume was contoured and segmented into sub-volumes based on their Standardized Uptake Values (SUV) in PET images. The sub-volumes with higher SUV were considered metabolically active and therefore required higher radiation dose. The integral tumor was prescribed a uniform dose from external beams followed by a boost dose delivered by HDR interstitial brachytherapy. The HDR treatment plan was optimized using a home-brew software implementation of an Adaptive Simulated Annealing (ASA) algorithm. The tumor dose was then redistributed by increasing and decreasing the prescription dose to sub-volumes with higher and lower SUV respectively such that the integral tumor prescription dose was kept constant. A routine cervical cancer case with both uniform and PET-guided plans is presented. Both plans were optimized based on a generalized Equivalent Uniform Dose (gEUD) cost function and renormalized to V100=95% of prescribed dose to the integral PTV. Their isodose distributions and DVHs were compared. Results: The PET-guided plan had larger hot spots in and near the PET sub-volume while the DVH of PTV was kept the same as that of the uniformly prescribed plan. Doses to critical organs were also reduced in the PET-guided plan. Conclusions: The approach described used PET/CT imaging guiding dose redistribution within PTV so that the hot spots encompass metabolically active tumor sub-volumes. An IRB approved treatment protocol is underway to study the clinical efficiency of this approach.