Citations

The purpose of this study was to evaluate the accuracy and calculation speed of electron dose distributions calculated by the Eclipse electron Monte Carlo (eMC) algorithm for use with bolus electron conformal therapy (ECT). The recent commercial availability of bolus ECT technology requires further validation of the eMC dose calculation algorithm. eMC‐calculated electron dose distributions for bolus ECT have been compared to previously measured TLD‐dose points throughout patient‐based cylindrical phantoms (retromolar trigone and nose), whose axial cross sections were based on the mid‐PTV (planning treatment volume) CT anatomy. The phantoms consisted of SR4 muscle substitute, SR4 bone substitute, and air. The treatment plans were imported into the Eclipse treatment planning system, and electron dose distributions calculated using 1% and statistical uncertainties. The accuracy of the dose calculations using moderate smoothing and no smoothing were evaluated. Dose differences (eMC‐calculated less measured dose) were evaluated in terms of absolute dose difference, where 100% equals the given dose, as well as distance to agreement (DTA). Dose calculations were also evaluated for calculation speed. Results from the eMC for the retromolar trigone phantom using 1% statistical uncertainty without smoothing showed calculated dose at of the measured TLD‐dose points was within 3% dose difference or 3 mm DTA of the measured value. The average dose difference was , and the net standard deviation was 2.32%. Differences as large as 3.7% occurred immediately distal to the mandible bone. Results for the nose phantom, using 1% statistical uncertainty without smoothing, showed calculated dose at of the measured TLD‐dose points within 3% dose difference or 3 mm DTA. The average dose difference was 1.08%, and the net standard deviation was 3.17%. Differences as large as 10% occurred lateral to the nasal air cavities. Including smoothing had insignificant effects on the accuracy of the retromolar trigone phantom calculations, but reduced the accuracy of the nose phantom calculations in the high‐gradient dose areas. Dose calculation times with 1% statistical uncertainty for the retromolar trigone and nose treatment plans were 30 s and 24 s, respectively, using 16 processors (Intel Xeon E5‐2690, 2.9 GHz) on a framework agent server (FAS). In comparison, the eMC was significantly more accurate than the pencil beam algorithm (PBA). The eMC has comparable accuracy to the pencil beam redefinition algorithm (PBRA) used for bolus ECT planning and has acceptably low dose calculation times. The eMC accuracy decreased when smoothing was used in high‐gradient dose regions. The eMC accuracy was consistent with that previously reported for accuracy of the eMC electron dose algorithm and shows that the algorithm is suitable for clinical implementation of bolus ECT.PACS number(s): 87.55.kd

The purpose of the present study was to compare the impact of pulmonary function, body habitus, and stereotactic body radiation therapy (SBRT) immobilization on setup and reproducibility for upper lung tumor. From 2008 through 2011, our institution's prospective SBRT database was searched for patients with upper lung tumors. Two SBRT immobilization strategies were used: full‐length BodyFIX and thermoplastic S‐frame. At simulation, free‐breathing, four‐dimensional computed tomography was performed. For each treatment, patients were set up to isocenter with in‐room lasers and skin tattoos. Shifts from initial and subsequent couch positions with cone‐beam computed tomography (CBCT) were analyzed. Accounting for setup uncertainties, institutional tolerance of CBCT‐based shifts for treatment was 2, 2, and 4 mm in left–right, anterior–posterior, and cranial–caudal directions, respectively; shifts exceeding these limits required reimaging. Each patient's pretreatment pulmonary function test was recorded. A multistep, multivariate linear regression model was performed to elucidate intervariable dependency for three‐dimensional calculated couch shift parameters. BodyFIX was applied to 76 tumors and S‐frame to 17 tumors. Of these tumors, 41 were non–small cell lung cancer and 15 were metastatic from other sites. Lesions measured , 1.1 to 2 (50%), 2.1 to 3 (25%), and cm. Errors from first shifts of first fractions were significantly less with S‐frame than BodyFIX (). No difference in local control (LC) was found between S‐frame and BodyFIX (); two‐year LC rate was 94%. Multivariate modeling confirmed that the ratio of forced expiratory volume in the first second of expiration to forced vital capacity, body habitus, and the immobilization device significantly impacted couch shift errors. For upper lung tumors, initial setup was more consistent with S‐frame than BodyFIX, resulting in fewer CBCT scans. Patients with obese habitus and poor lung function had more SBRT setup uncertainty; however, outcome and probability for LC remained excellent.PACS number: 89.20.‐a

The purpose of this study is to investigate changes in lung tumor internal target volume during stereotactic body radiotherapy treatment (SBRT) using magnetic resonance imaging (MRI). Ten lung cancer patients (13 tumors) undergoing SBRT (48 Gy over four consecutive days) were evaluated. Each patient underwent three lung MRI evaluations: before SBRT (MRI‐1), after fraction 3 of SBRT (MRI‐3), and three months after completion of SBRT (MRI‐3m). Each MRI consisted of T1‐weighted images in axial plane through the entire lung. A cone‐beam CT (CBCT) was taken before each fraction. On MRI and CBCT taken before fractions 1 and 3, gross tumor volume (GTV) was contoured and differences between the two volumes were compared. Median tumor size on CBCT before fractions 1 (CBCT‐1) and 3 (CBCT‐3) was 8.68 and 11.10 cm3, respectively. In 12 tumors, the GTV was larger on CBCT‐3 compared to CBCT‐1 (median enlargement, 1.56 cm3). Median tumor size on MRI‐1, MRI‐3, and MRI‐3m was 7.91, 11.60, and 3.33 cm3, respectively. In all patients, the GTV was larger on MRI‐3 compared to MRI‐1 (median enlargement, 1.54 cm3). In all patients, GTV was smaller on MRI‐3m compared to MRI‐1 (median shrinkage, 5.44 cm3). On CBCT and MRI, all patients showed enlargement of the GTV during the treatment week of SBRT, except for one patient who showed minimal shrinkage (0.86 cm3). Changes in tumor volume are unpredictable; therefore, motion and breathing must be taken into account during treatment planning, and image‐guided methods should be used, when treating with large fraction sizes.PACS number: 87.53.Ly

In the present work, we investigated the accuracy of the electron pencil‐beam redefinition algorithm (PBRA) in calculating central‐axis percent depth dose in water for rectangular fields. The PBRA energy correction factor C(E) was determined so that PBRA‐calculated percent depth dose best matched the percent depth dose measured in water. The hypothesis tested was that a method can be implemented into the PBRA that will enable the algorithm to calculate central‐axis percent depth dose in water at a 100‐cm source‐to‐surface distance (SSD) with an accuracy of 2% or 1‐mm distance to agreement for rectangular field sizes cm. Preliminary investigations showed that C(E), determined using a single percent depth dose for a large field (that is, having side‐scatter equilibrium), was insufficient for the PBRA to accurately calculate percent depth dose for all square fields cm. Therefore, two alternative methods for determining C(E) were investigated. In Method 1, C(E), modeled as a polynomial in energy, was determined by fitting the PBRA calculations to individual rectangular‐field percent depth doses. In Method 2, C(E) for square fields, described by a polynomial in both energy and side of square W [that is, ], was determined by fitting the PBRA calculations to measured percent depth dose for a small number of square fields. Using the function C(E, W), C(E) for other square fields was determined, and C(E) for rectangular field sizes was determined using the geometric mean of C(E) for the two measured square fields of the dimension of the rectangle (square root method). Using both methods, PBRA calculations were evaluated by comparison with measured square‐field and derived rectangular‐field percent depth doses at 100‐cm SSD for the Siemens Primus radiotherapy accelerator equipped with a ‐cm applicator at 10 MeV and 15 MeV. To improve the fit of C(E) and C(E, W) to the electron component of percent depth dose, it was necessary to modify the PBRA's photon depth dose model to include dose buildup. Results showed that, using both methods, the PBRA was able to predict percent depth dose within criteria for all square and rectangular fields. Results showed that second‐ or third‐order polynomials in energy (Methods 1 and 2) and in field size (Method 2) were typically required. Although the time for dose calculation using Method 1 is approximately twice that using Method 2, we recommend that Method 1 be used for clinical implementation of the PBRA because it is more accurate (most measured depth doses predicted within approximately 1%) and simpler to implement.PACS number: 87.53.Fs

1 Background: Endoscopic resection (ER) is used to treat early esophageal cancers (EAC). With the advent of techniques such as ESD that can remove large lesions en bloc, it is important to determine if performing piecemeal resections of intramucosal cancers is detrimental. Aim: To evaluate the response rates in patients with esophageal intramucosal adenocarcinoma (IMC) who had a single ER (SR) compared to those treated with piecemeal resection (PR). Methods: This is a cohort study of patients being followed in our BE unit. Patients in a prospectively maintained database with EAC from Jan 1998 to Apr 2012 were assessed. IMC was defined as lesions that were intramucosal without extension into the submucosa. All T1a cancers were verified by two expert gastrointestinal pathologists. We compared the tumor characteristics and recurrence rate between the two groups of SR and PR of IMC. Results: A total of 197 IMC (T1a) lesions in 138 patients were identified. 88(44.7%) lesions were performed SR and 109(55.3%) were PR. Mean follow up time were 45 months (IQR 24-70.5) in SR and 39 months (IQR 26-52, P=0.067) in PR. Complete remission were found of 92.1% (81) in SR and of 93.6% (102) in PR (P=0.788) patients. The recurrence rate was 7.9% in the SR patients, and 6.4% in the PR patients (P=0.699). Median time to progression was 12 months in the SR group (IQR 8-23.5) and 11 months in the PR (IQR 8-22) (P=0.765) group. The mean survival duration was 116.3 months in the SR and 89 months in the PR (P=0.079). No statistical difference in 5-year survival rates was found between SR (83.2%) and PR (80.9%) (P=0.082). Cox proportional hazard model analysis showed local recurrence after EMR was not related to number of specimen resected or technique. Conclusions: PR appears to be as effective a therapy as en bloc for esophageal IMC. Using PR does not appear to affect clinical outcomes.

LBA2010 Background: RTOG 0825 evaluated the addition of BEV to standard CRT in the treatment of GBM and included molecular stratification that assessed the degree of mesenchymal (MES) gene enrichment. We investigated the ability of the MES signature to predict response to BEV. Methods: Sufficient FFPE tissue for molecular analysis was available for 650 registered, eligible patients. TaqMan PCR was performed prospectively using the molecular stratifier on all patients and an expanded 43 member MES set on 234 cases. A subset of specimens was subjected to whole genome expression profiling (GEP). Predictive models were evaluated for their ability to predict survival (overall, OS, and progression-free, PFS) in the training cohort of the BEV arm after adjusting for prognostic factors and treatment arm. Unsupervised clustering of GEP data was used to identify molecular subsets and gene set enrichment analysis (GSEA) performed to evaluate for MES enrichment. Results: We observed a significant association between increasing MES signature and worse PFS and OS in the BEV arm (p=0.036 and p=0.032, respectively). Based on the association between high MES expression and poor outcome in the BEV arm, we sought to optimize a predictor using an expanded set of MES genes. Unbiased gene selection from a total of 43 genes followed by radial basis machine modeling identified a 10-gene predictor of outcome in the BEV arm (p<0.001/HR 4.04 for OS and p<0.001/HR 2.21 for PFS). To further support the association of MES enrichment and poor outcome in the BEV arm, we performed GEP. Unsupervised clustering identified a subtype of tumors with MES enrichment associated with the 10-gene predictor survival probability (p=0.0124, t-test). Ongoing studies will determine the extent to which this represents a predictive marker for BEV. Conclusions: We developed a 10-gene predictor specific to BEV treatment and suitable for FFPE that may serve to identify subsets of patients with newly diagnosed GBM who benefit from BEV. Supported by RTOG grant U10 CA21661, CCOP grant U10 CA37422, and Brain SPORE P50 CA127001 from the NCI and Genentech. Clinical trial information: NCT00884741.

1 Background: Chemoradiation (CRT) with temozolomide (TMZ/RT→TMZ) is the standard of care for newly diagnosed GBM. This trial determined if the addition of Bev to standard CRT improves survival (OS) or progression-free survival (PFS) in newly diagnosed GBM. Methods: This phase III trial was conducted by the RTOG, NCCTG, and ECOG. Neurologically stable pts > 18 yrs with KPS ≥ 60, and > 1cm3 tumor tissue block, were randomized to Arm 1: standard CRT + placebo or Arm 2: standard CRT plus Bev (10 mg/kg iv q 2wks). Experimental treatment began at wk 4 of radiation then thru 6-12 cycles of maintenance chemotherapy. Protocol specified co-primary endpoints were OS and PFS, with significance levels of .023 and .002, respectively. At progression, treatment was unblinded and pts allowed to crossover or continue Bev. Symptom, QOL and neurocognitive (NCF) testing was performed in the majority of pts. Secondary analyses evaluated impact of MGMT methylation (meth) and prognostic 9 gene signature status. Results: From 978 registered pts, 637 were randomized. Inadequate tissue (n=105) and blood on imaging (n=40) were key reasons for non-randomization. No difference was found between arms for OS (median 16.1 vs. 15.7 mo, p = 0.11). PFS was extended for Arm 2 (7.3 vs. 10.7 mo, p = 0.004). Pts with MGMT meth had superior OS (23.2 vs. 14.3 mo, p < 0.001) and PFS (14.1 vs. 8.2 mo, p < 0.001). Neither the 9 gene signature nor MGMT predicted selective benefit for Bev treatment, but best prognosis pts (MGMT meth, favorable 9-gene), had a worse survival trend with Bev (15.7 vs 25 mo p = 0.08). To date, 128 pts were unblinded on Arm 1 (salvage Bev in 86) and 87 pts on Arm 2 (continued Bev in 39). Increased grade ≥ 3 toxicity was seen with Bev, mostly neutropenia, hypertension, and DVT/PE. Conclusions: The addition of Bev for newly diagnosed GBM did not improve OS, did improve PFS but did not reach the significance criterion. MGMT and 9 gene profile did not identify selective benefit, but risk subset results suggested strongly against the upfront use of Bev in the best prognosis pts. Full interpretation of the PFS results incorporating symptom burden, QOL, and NCF is ongoing. Support: NCI U10 CA 21661, U10 CA37422, and Genentech. Clinical trial information: NCT00884741.