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Purpose This study was undertaken to identify parameters associated with hematologic toxicity or chemotherapy dose modification in patients undergoing concurrent chemoradiation (CRT) with gemcitabine for localized pancreatic cancer. Methods and materials We reviewed patients with localized pancreatic cancer undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of nongemcitabine therapy, chemotherapy before CRT, or abnormal baseline hematologic indices. The T11-L3 vertebrae were contoured as bone marrow region at risk. Linear and logistic regression models were used to test associations between dosimetric parameters and gemcitabine dose modification or hematologic toxicity during or within 3 months following CRT. Receiver operator curves were generated to identify threshold doses for hematologic toxicity. Results Forty-nine patients were included. During CRT, the maximum thoracolumbar dose was associated with grade 2+ neutropenia during CRT ( P = .017) and the volume receiving 5 Gy (V5) was associated with grade 2+ leukopenia ( P = .041). Post-CRT, thoracolumbar mean dose ( P = .015), V5 ( P = .01), and V10 ( P = .012) were associated with increased grade 2+ neutropenia. On multivariable analysis, the thoracolumbar maximum dose ( P = .045) and V5 ( P = .045) were associated with grade 2+ neutropenia and grade 2+ leukopenia during CRT, respectively. Post-CRT, the mean dose ( P = .046), V5 ( P = .019), and V10 ( P = .037) were associated with increased grade 2+ neutropenia. A maximum dose of 48.02 Gy and V5 of 57.6% were identified as predictors of toxicity during CRT. A V5 of 56.6%, V10 of 47.05%, and mean dose of 11.67 Gy were identified as predictors of post-CRT hematologic toxicity. Post-CRT, there was a trend toward increased dose modifications with increased V5 ( P = .065). Conclusions In our dataset, the thoracolumbar mean dose, maximum dose, V5, and V10 correlated with hematologic toxicity during CRT and post-CRT in patients with localized pancreatic cancer. Because of the high rates of distant failure and importance of systemic therapy in these patients, this may be an important consideration during treatment planning.

Purpose To estimate the overall survival (OS) impact from increasing time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC). Methods Using the National Cancer Data Base (NCDB), we examined patients who received curative therapy for the following sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was the number of days from diagnosis to initiation of curative treatment. The effect of TTI on OS was determined by using Cox regression models (MVA). Recursive partitioning analysis (RPA) identified TTI thresholds via conditional inference trees to estimate the greatest differences in OS on the basis of randomly selected training and validation sets, and repeated this 1,000 times to ensure robustness of TTI thresholds. Results A total of 51,655 patients were included. On MVA, TTI of 61 to 90 days versus less than 30 days (hazard ratio [HR], 1.13; 95% CI, 1.08 to 1.19) independently increased mortality risk. TTI of 67 days appeared as the optimal threshold on the training RPA, statistical significance was confirmed in the validation set (P < .001), and the 67-day TTI was the optimal threshold in 54% of repeated simulations. Overall, 96% of simulations validated two optimal TTI thresholds, with ranges of 46 to 52 days and 62 to 67 days. The median OS for TTI of 46 to 52 days or fewer versus 53 to 67 days versus greater than 67 days was 71.9 months (95% CI, 70.3 to 73.5 months) versus 61 months (95% CI, 57 to 66.1 months) versus 46.6 months (95% CI, 42.8 to 50.7 months), respectively (P < .001). In the most recent year with available data (2011), 25% of patients had TTI of greater than 46 days. Conclusion TTI independently affects survival. One in four patients experienced treatment delay. TTI of greater than 46 to 52 days introduced an increased risk of death that was most consistently detrimental beyond 60 days. Prolonged TTI is currently affecting survival.

Purpose To assess the relationship between tumor-specific growth rate (TSGR) and oropharyngeal cancer (OPC) outcomes in the HPV era. Methods/materials Primary tumor volume differences between a diagnostic and secondary scan separated ⩾⩾7 days without interval treatment were used to estimate TSGR, defined as percent volume growth/day derived from primary tumor volume doubling time for 85 OPC patients with known p16 status and smoking pack-years managed with (chemo)radiation. Variables were analyzed using Kruskal–Wallis or Fisher’s exact test as appropriate. Log-rank tests and Cox proportional models analyzed endpoints. Using concordance probability estimates (CPE), TSGR was incorporated into RTOG 0129 risk grouping (0129RG) to assess whether TSGR could improve prognostic accuracy. Results Median time between scans was 35 days (range 8–314). Median follow up was 26 months (range 1–76). The 0129RG classification was: 56% low, 25% intermediate, and 19% high risk. Median TSGR was 0.74%/day (range 0.01–4.25) and increased with 0129RG low (0.41%), intermediate (0.57%) and high (1.23%) risk, respectively (p = 0.015). TSGR independently predicted for TF (TSGR: HR (95%CI) = 2.79, 1.67–4.65, p

Background Randomized data examining adjuvant radiation therapy (RT) alone in elderly women with low-risk, hormone receptor-positive (HR + ) breast cancer is lacking. We investigated the outcomes for elderly women treated with adjuvant RT alone versus RT plus endocrine therapy (ET) after breast-conserving surgery. Patients and Methods We queried our institutional breast cancer database for the following patients: age > 65 years, stage T1-T2N0, HR + , and treatment with breast-conserving surgery, including adjuvant RT. The χ 2 analysis identified significant baseline differences between the groups. Cox proportional hazard methods identified predictors of endpoints on multivariate analysis. Kaplan-Meier estimates of survival were compared using the log-rank test. Results A total of 504 patients were identified, 311 had undergone RT plus ET (62%) and 193, RT alone (38%). The median follow-up time was 88 months. The RT-alone group versus RT plus ET group had different median age (72 vs.71 years, P P P = .05), and fewer close or positive margins (11% vs. 19%, P = .01). The adherence rate to prescribed ET was 70%. Tumor size predicted an increased risk of distant metastasis (DM) (hazard ratio, 1.96; 95% confidence interval [CI], 1.23-3.13) and worse disease-free survival (DFS) (hazard ratio, 1.86; 95% CI, 1.22-2.86). ET nonadherence versus adherence predicted for risk of DM (hazard ratio, 5.03; 95% CI, 1.98-12.66) and DFS (HR, 4.24; 95% CI, 1.9-10.3). Of the women with DM, 83.8% had tumors > 1 cm in size. Conclusion ET nonadherence and tumor size > 1 cm predicted an increased risk of DM and worse DFS, favoring the addition of ET in this group. However, RT alone for women with tumors less than or equal to 1 cm may be appropriate.

Purpose Patients with pancreatic adenocarcinoma (PAC) are often treated with neoadjuvant chemoradiation (NACRT) in hopes of downstaging their disease for potential surgical resection. We hypothesized that increasing the radiation dose to the area of the tumor abutting the vessel(s) of concern would increase the rate of surgical resection in patients with borderline resectable PAC (BRPAC) and locally advanced PAC (LAPAC) treated with NACRT. Methods and materials We retrospectively reviewed consecutive cases of BRPAC and LAPAC treated with NACRT from January 2006 to December 2013, with or without a vessel boost (VB), at a single institution. The primary endpoints were rate of R0/R1 potentially curative surgical resection and acute toxicity. Univariate analysis with the Fisher exact test was performed to evaluate the effect of each variable. Multiple logistic regression was used to adjust for the following covariates: year of diagnosis, age, sex, carbohydrate antigen 19-9 (CA19-9) level at diagnosis, and BRPAC or LAPAC. Results Of the 104 patients identified, 22% (n = 23) received a VB (median, 54 Gy; range, 54-64 Gy), and 78% (n = 81) received no boost (median, 50.4 Gy; range, 48.6-52.2 Gy). More patients in the VB group were treated from 2010 to 2013 ( P P = .002). Other baseline characteristics were balanced. After adjustment for covariates, there was a statistical trend toward increased surgical resection in patients who received a VB (odds ratio [OR], 2.77; 95% confidence interval [CI], 0.89-8.57; P = .077). Age (≥70 years; OR, 0.42; 95% CI, 0.16-1.05; P = .064) and LAPAC (OR, 0.32; 95% CI, 0.09-1.09; P = .068) also trended toward significance. CA19-9 ≥47.9 U/mL (OR, 0.24; 95% CI, 0.08-0.71; P = .010) was significant on multivariate analysis. There was no significant difference in acute or late toxicity between groups. Conclusions In our retrospective series, dose escalation was associated with an improved surgical resection rate in BRPAC and LAPAC patients treated with NACRT, although this improvement was not statistically significant.

BACKGROUND Previous publications have demonstrated conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy (RT) before the dose escalation era. The goal of the current study was to determine whether increasing BMI was associated with outcomes in men with localized CaP who were treated with dose-escalated RT. METHODS The authors identified patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity-modulated RT and image-guided RT from 2001 through 2010. BMI was analyzed as a continuous variable. Adjusting for confounders, multivariable competing risk and Cox proportional hazards regression models were used to assess the association between BMI and the risk of biochemical failure (BF), distant metastases (DM), cause-specific mortality (CSM), and overall mortality. RESULTS Of the 1442 patients identified, approximately 20% had a BMI

Purpose: There are two collimation systems associated with the CyberKnife system, the fixed cone collimator and the Iris collimator. The Iris collimator is used more frequently because of its superior flexibility. However, sometimes treatments have to be canceled or postponed due to Iris collimator mechanical failures. The purpose of this study is to investigate the feasibility of switching collimation systems without replanning. Methods: We first performed Monte Carlo simulations on 10 clinical cases using the Iris collimator and the fixed cone collimator. The conformality index (CI), target volume coverage and the maximum, minimum and mean doses to the critical structures from the iris and fixed plans were compared to determine the feasibility of switching between collimator types without replanning. Results: Our results showed that the two types of collimators deliver similar dose distributions. The average target doses for the fixed plans were 1% to 6% higher than those for the Iris plans. The average CI for the fixed plans was 1.36 compared to 1.28 for the Iris plans. Thus, we adjusted the Iris sizes with a scale factor of 1.024 to achieve a better dose match with the fixed collimators. Doses for the 10 cases were then recalculated. Once this correction was made, the difference between the average target doses for the two collimator plans was reduced to less than 2% and the CIs became almost identical. Conclusions: Small target dose differences were found between plans using different collimation systems, which may be compensated for by adjusting the Iris collimator sizes to ensure similar dose distributions. The differences in the doses to the critical structures between the collimation systems were insignificant. After adjusting the Iris collimator sizes and re‐commissioning the planning system, patients can be safely switched from the Iris collimator to the fixed cone collimator without replanning.

There has been no consensus standard of care to treat recurrent cancer patients who have previously been irradiated. Pulsed low dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while still providing significant tumor control for recurrent cancers. This work investigates the dosimetry feasibility of PLDR treatment using dynamic arc delivery techniques. Five treatment sites were investigated in this study including breast, pancreas, prostate, head and neck, and lung. Dynamic arc plans were generated using the Varian Eclipse system and the RapidArc delivery technique with 6 and 10 MV photon beams. Each RapidArc plan consisted of two full arcs and the plan was delivered five times to achieve a daily dose of 200 cGy. The dosimetry requirement was to deliver approximately 20 cGy/arc with a 3 min interval to achieve an effective dose rate of 6.7 cGy min⁻¹. Monte Carlo simulations were performed to calculate the actual dose delivered to the planning target volume (PTV) per arc taking into account beam attenuation/scattering and intensity modulation. The maximum, minimum and mean doses to the PTV were analyzed together with the dose volume histograms and isodose distributions. The dose delivery for the five plans was validated using solid water phantoms inserted with an ionization chamber and film, and a cylindrical detector array. Two intensity-modulated arcs were used to efficiently deliver the PLDR plans that provided conformal dose distributions for treating complex recurrent cancers. For the five treatment sites, the mean PTV dose ranged from 18.9 to 22.6 cGy/arc. For breast, the minimum and maximum PTV dose was 8.3 and 35.2 cGy/arc, respectively. The PTV dose varied between 12.9 and 27.5 cGy/arc for pancreas, 12.6 and 28.3 cGy/arc for prostate, 12.1 and 30.4 cGy/arc for H&N, and 16.2 and 27.6 cGy/arc for lung. Advanced radiation therapy can provide superior target coverage and normal tissue sparing for PLDR reirradiation of recurrent cancers, which can be delivered using dynamic arc delivery techniques with ten full arcs and an effective dose rate of 6.7 ± 4.0 cGy min⁻¹.

Locoregionally advanced nonmelanoma skin cancer (NMSC) has an aggressive clinical course characterized by high rates of treatment failure and poor survival compared with localized skin cancers. Our goal was to investigate multimodal therapy for lymph-node-positive NMSC. Data from patients with lymph-node-positive NMSC who underwent surgery and adjuvant therapy at a single tertiary center from 2002 to 2012 were retrospectively reviewed. Median follow-up was 1.8 years (range: 0.5 to 8.5). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. The chi-square test and logistic regression were used to determine the association between locoregional control (LRC) and the following variables: evidence of extracapsular extension, number of lymph nodes positive, largest involved lymph node, presence of a positive margin, and use of concurrent chemoradiation (CRT). Forty-six patients were evaluated, 13 (28%) of whom received adjuvant CRT. CRT patients were younger (p < 0.001) and had a significantly greater number of positive lymph nodes (p = 0.016) than patients who received adjuvant radiation alone. At 5 years, LRC was 76%, PFS was 65%, and OS was 49%. Univariate analysis demonstrated that CRT (p = 0.006), largest lymph node measurement (p = 0.039), and ≥3 involved lymph nodes (p = 0.001) predicted local recurrence. CRT (p = 0.035, odds ratio [OR] 0.20 [95% confidence interval 0.05 to 0.90]) and ≥3 involved lymph nodes (p = 0.017, OR 0.07 [95% confidence interval 0.01 to 0.62]) remained significant on multivariate analysis. CRT was well tolerated. No grade ≥3 toxicities were observed except for 1 asymptomatic grade-4 thrombocytopenia. Patients with lymph-node-positive NMSC do poorly. Patient selection for intensification of adjuvant therapy needs clarification.

Short hairpin RNAs (shRNAs) have emerged as a novel therapeutic modality, but there is increasing concern over nonspecific effects in vivo. Here, we used viral vectors to express shRNAs against endogenous p53 in livers of conditional MYC-transgenic mice. As expected, the shRNAs silenced hepatic p53 and accelerated liver tumorigenesis when MYC was concurrently expressed. Surprisingly, various irrelevant control shRNAs similarly induced a rapid onset of tumorigenesis, comparable to carbon tetrachloride (CCl4), a potent carcinogen. We found that even marginal shRNA doses can already trigger histologically detectable hepatoxicity and increased hepatocyte apoptosis. Moreover, we noted that shRNA expression globally dysregulated hepatic microRNA (miRNA) expression, and that shRNA levels and activity further increased in the presence of MYC. In MYC-expressing transgenic mice, the marginal shRNA-induced liver injury sufficed to further stimulate hepatocellular division that was in turn associated with markedly increased expression of the mitotic cyclin B1. Hence, even at low doses, shRNAs can cause low-level hepatoxicity that can facilitate the ability of the MYC oncogene to induce liver tumorigenesis. Our data warrant caution regarding the possible carcinogenic potential of shRNAs when used as clinical agent, particularly in circumstances where tissues are genetically predisposed to cellular transformation and proliferation.

Accurate dosimetry of the narrow beam tends to be difficult to perform due to the absence of lateral electronic equilibrium and the steep dose gradient, as well as the finite size of detectors. Thus, although the high dose rate 6 MV beam on the VARIAN Trilogy accelerator is increasingly utilized for stereotactic radiosurgery (SRS) treatment, there is no general agreement in the SRS beam output factor values among the Trilogy user community. Trilogy SRS beams are confined by cone collimators and the available collimator sizes range from 5 and 10 to 30 mm, in every 2 mm increment. A range of the relative output factors are in clinic use. This variation may impair observations of dose response and optimizations of the prescribed dose. It is necessary to investigate an accurate, easily performable, and detector independent method for the narrow beam output factor measurement. In this study, a scanning beam/scanning chamber method was proposed to overcome the limitation/difficulty of using a relatively large detector in narrow beam output factor measurement. Specifically, for the scanning beam method, multiple narrow beams are used for the dose measurement using a finite size chamber. These multiple scanning beams form an equivalent large uniform field whichmore » provides lateral electron equilibrium condition. After the measurement, the contributions from neighboring beams are deconvolved and the value is used for output factor determinations. For a Linac that cannot move a beam laterally, the scanning chamber method can be used to achieve the same result. The output factors determined in such a method were compared to chambers (a 0.015 cc PTW PinPoint ion chamber and a 0.125 cc PTW ion chamber) and film measurement, as well as with Monte Carlo simulation. Film and Monte Carlo results are found to be in excellent agreement with the measurement using the scan beam method. However, the VARIAN recommended output factors measured directly by Wellhoefer CC01 chamber and Scanditronix photon field diode are consistently higher for all the cones. Especially for the 5 mm cone, the difference is more than 10%. Overall, the results suggested that the new method can help overcoming the detector volume averaging effect and the positioning uncertainties, which constitute the major challenge in small radiosurgical beam output factor measurement, and provide reliable output factors.« less

Modulated electron radiotherapy (MERT) may potentially be an effective modality for the treatment of shallow tumors, but dose calculation accuracy and delivery efficiency challenges remain. The purpose of this work is to investigate the dose accuracy of MERT delivery using a photon multileaf collimator (pMLC) on a Siemens Primus accelerator. A Monte Carlo (MC)-based inverse treatment planning system was developed for the 3D treatment planning process. Phase space data of 6, 9, 12 and 15 MeV electron beams were commissioned and used as the input source for MC dose calculations. A treatment plan was performed based on the 3D CT data of a heterogeneous 'breast phantom' that mimics a breast cancer patient, and delivered with 22 segments, each associated with a particular energy and Monitor Unit value. Film and ion chamber dosimetry was carefully performed for the conversion from measurement reading to dose, and the results were employed for plan verification using the heterogeneous breast phantom and a solid water phantom. Dose comparisons between measurements and calculations showed agreement within 2% or 1 mm. We conclude that our in-house MC treatment planning system is capable of performing treatment planning and accurate dose calculations for MERT using the pMLC to deliver radiation therapy to the intact breast.

This work investigated the selection of beam margins in lung-cancer stereotactic body radiotherapy (SBRT) with 6 MV photon beams. Monte Carlo dose calculations were used to systematically and quantitatively study the dosimetric effects of beam margins for different lung densities (0.1, 0.15, 0.25, 0.35 and 0.5 g cm(-3)), planning target volumes (PTVs) (14.4, 22.1 and 55.3 cm3) and numbers of beam angles (three, six and seven) in lung-cancer SBRT in order to search for optimal beam margins for various clinical situations. First, a large number of treatment plans were generated in a commercial treatment planning system, and then recalculated using Monte Carlo simulations. All the plans were normalized to ensure that 95% of the PTV at least receives the prescription dose and compared quantitatively. Based on these plans, the relationships between the beam margin and quantities such as the lung toxicity (quantified by V20, the percentage volume of the two lungs receiving at least 20 Gy) and the maximum target (PTV) dose were established for different PTVs and lung densities. The impact of the number of beam angles on the relationship between V20 and the beam margin was assessed. Quantitative information about optimal beam margins for lung-cancer SBRT was obtained for clinical applications.

Intensity-modulated radiation therapy (IMRT) has been shown to decrease abdominal toxicity in patients undergoing chemoradiation (CRT) for pancreatic cancer. We evaluated whether IMRT impacts the rates of hematologic toxicity and chemotherapy dose intensity in patients undergoing CRT. We retrospectively reviewed patients with borderline resectable or locally advanced pancreatic cancer undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of non-gemcitabine therapy, chemotherapy before CRT, or abnormal baseline hematologic indices. Endpoints included total gemcitabine dose received, dose intensity, unplanned dose reductions, and hematologic toxicity (WBC, ANC, platelet, and hemoglobin). Patient/treatment factors were evaluated for their relationship to the above endpoints during CRT and within the first 3 months post-CRT. Statistical analysis was performed using the Fisher exact test and regression models. Because of the multiple comparisons in the presented analysis, a false discovery rate adjustment was performed at the 5% false discovery rate level. Eighty-five patients met the inclusion criteria. Fifty-eight (68.2%) patients received treatment with IMRT, and 27 (31.8%) patients were treated with 3D-conformal radiation. During CRT, there was no relationship between radiation technique and gemcitabine dose received, dose intensity, or hematologic grade 3+ toxicity. Post-CRT, there was no relationship between radiation technique and total gemcitabine dose received, dose intensity, or dose reduction. Patients receiving IMRT were more likely to have ANC grade 3+ toxicity (P=0.007) post-CRT, although this was no longer statistically significant after correction. There were no other relationships between treatment technique and hematologic toxicity. IMRT technique may be associated with higher hematologic toxicity in patients undergoing CRT for pancreatic cancer. Given the expanding use of CRT, additional study is needed to identify the impact of IMRT on myelosuppression in these patients.

Skin adnexal carcinoma (SAC) is a rare cutaneous malignancy that arises from sebaceous and sweat glands. These carcinomas are believed to behave more aggressively than cutaneous squamous cell carcinomas (SCC) with a propensity for local recurrence. The role of adjuvant radiotherapy in SAC is undefined.We retrospectively reviewed all cases of head and neck SAC treated with surgery and adjuvant radiation from 2000 to 2012 at a single institution.Nine cases were identified. Median age was 67 (range, 52 to 88) years. The histologies were: adnexal carcinoma (n=1), adnexal carcinoma with sebaceous differentiation (n=1), adnexal carcinoma with squamous differentiation (n=1), skin appendage carcinoma (n=1), sclerosing sweat duct carcinoma (n=1), mucinous carcinoma (n=1), ductal eccrine adenocarcinoma (n=1), porocarcinoma (n=1), and trichilemmal carcinoma (n=1). All tumors were reviewed by a dermatopathologist to confirm the SAC diagnosis.All patients had undergone surgery. Indications for adjuvant radiation included involved lymph nodes (n=4), perineural invasion (n=2), nodal extracapsular extension (n=2), positive margin (n=1), high-grade histology (n=6), multifocal disease (n=2), and/or recurrent disease (n=5). Radiation was delivered to the primary site alone (n=3), to the draining lymphatics alone (n=2), or to both (n=4). One patient received concurrent cisplatin. Median dose to the primary site was 60 Gy and to the neck was 50 Gy.Median follow-up was 4.0 years (range, 0.6 to 11.4 y). Locoregional control was 100%. Five-year progression-free survival was 89%. There was 1 acute grade 3 toxicity and no greater than or equal to grade 2 late toxicities were recorded.Surgery and adjuvant radiation for high-risk SAC offers excellent locoregional control with acceptable toxicity.

A Monte Carlo based intensity-modulated radiation therapy (IMRT) treatment planning system has been developed and used for breast treatment. An iterative method was used for optimization to generate IMRT plans and a step-and-shoot technique was used for beam delivery. The patient setup and incident beam directions were the same as those for conventional tangential photon treatment. The weights for the opposed beamlets in the two tangential beams were determined first by the doses at the depths of the maximum dose at both sides to minimize hot spots. The intensity of an individual beamlet pair was then optimized based on the dose at the midplane. Fine tuning was made to achieve optimal target dose uniformity and to reduce the dose to the heart when necessary. The final dose calculations were performed using the Monte Carlo method and the plans were verified by phantom measurements. The dose distributions and dose-volume-histograms of IMRT plans were compared with those of conventional plans that were generated using a commercial treatment planning system and recalculated using an in-house Monte Carlo system for the first 25 patients. The dose comparisons showed that the percentage volume receiving more than 95% of the prescription dose (V95) and the percentage volume receiving more than 100% of the prescription dose (V100) for the clinical target volume (CTV) of IMRT plans were about the same as those of conventional plans. The percentage volume receiving more than 105% of the prescription dose (V105) for the CTV was reduced from 23.1% to 7.9% on average. The percentage volume of the lung receiving more than 20 Gy dose (V20 Gy) during the entire treatment was reduced by about 10%. The percentage volume of the heart receiving more than 30 Gy dose (V30 Gy) is reduced from 3.3% to 0.3%. Further studies revealed that a less than 5 degrees change in couch angle and collimator angle at patient setup had no significant effect on the dose coverage of CTV but had significant effect on the dose to the lung and heart. The study on the effect of beam spoiler showed that it increased the dose at the buildup region by 0- 13% that varies with location. The machine output linearity and stability for small monitor unit delivery of Siemens accelerators used for this study was checked and found to be suitable for breast IMRT. The total effect of variations was calculated to be less than 1% for typical breast treatments. The beam delivery time was increased by about 2 min compared with conventional tangential treatments. The whole treatment including patient setup and beam delivery can be completed in a 15 min slot. The IMRT technique has been proven practical for breast treatment clinically. The results showed that tangential IMRT improved the dose homogeneity in the breast and reduced the dose to the lung and heart.

In this work, we investigate a formalism for monitor unit (MU) calculation in Monte Carlo based treatment planning. By relating MU to dose measured under reference calibration conditions (central axis, depth of dose maximum in water, 10 cm x 10 cm field defined at 100 cm source-to-surface distance) our formalism determines the MU required for a treatment plan based on the prescription dose and Monte Carlo calculated dose distribution. Detailed descriptions and formulae are given for various clinical situations including conventional treatments and advanced techniques such as intensity-modulated radiotherapy (IMRT) and modulated electron radiotherapy (MERT). Analysis is made of the effects of source modelling, beam modifier simulation and patient dose calculation accuracy, all of which are important factors for absolute dose calculations using Monte Carlo simulations. We have tested the formalism through phantom measurements and the predicted MU values were consistent with measured values to within 2%. The formalism has been used for MU calculation and plan comparison for advanced treatment techniques such as MERT, extracranial stereotactic IMRT, MRI-based treatment planning and intensity-modulated laser-proton therapy studies. It is also used for absolute dose calculations using Monte Carlo simulations for treatment verification, which has become part of our comprehensive IMRT quality assurance programme.

There are several localization techniques that have been used for prostate treatment. Recently, the potential use of a variety of CT-based equipment in the treatment room has been discussed. The goal of our study was to develop an automated procedure for daily treatment table shift calculation based on two CT data sets: simulation CT data and localization CT data. The method suggested in this study is a 3D image cross-correlation of small regions of interest (ROI) within the two data sets. The relative position of the two ROIs with respect to each other is determined by the maximum value of the normalized cross-correlation function, calculated for all possible relative locations of the two ROIs. After the best match is found the shifts are given by the vector connecting the treatment isocentre and the planning isocentre (both determined by the radio opaque fiducial markers on the patient's skin). The results have been compared with shifts calculated through manual fusion. The shift differences, averaged over 17 statistically independent shift calculations, are less then 1 mm in the lateral and longitudinal directions, and about 1 mm in the AP direction. The impact of image noise on the performance of the algorithm has been tested. The results show that the algorithm accurately adjusts for target positional changes even with Gaussian noise levels as high as 20% inserted.

The GaN/AlGaN multi-quantum-wells (MQWs) have been grown via metalorganic chemical vapor deposition (MOCVD). Micro-photoluminescence (PL) measurement has been performed on non-, In- and Si- doped GaN/AlGaN MQW samples in the temperature ranges of 90-300 K. In the non-doped GaN/AlGaN MQWs we observed the free exciton peak at 3.4587 eV at 90 K. Other exciton related, peaks are located at 3.4346, 3.4177, 3.394 and 3.3129 eV, which are probably associated with the strongly localized excitons involving the defects. In In-doped GaN/AlGaN MQWs, the free exciton peaks have a slight red-shift from 3.4712 to 3.4629 eV, but the PL intensities become stronger with increasing trimethylindium (TMIn) flow from 10.6 to 42.6 μmol min - 1 . With Si-doping in the well layers, PL exhibits an envelope of exciton bands ranged from 3.4796 (free exciton) to 3.43915 eV. The excitonic peaks in the bands vary in intensity and position with sample temperature. In addition, we have also observed the LO phonon replica of AlGaN interacted by the laser line due to the resonance effect.

Purpose: Liver SBRT patients unable to tolerate breath-hold for radiotherapy are treated free-breathing with image guidance. Target localization using 3D CBCT requires extra margins to accommodate the respiratory motion. The purpose of this study is to evaluate the accuracy and reproducibility of 4D CT-on-rails in target localization for free-breathing liver SBRT. Methods: A Siemens SOMATOM CT-on-Rails 4D with Anzai Pressure Belt system was used both as the simulation and the localization CT. Fiducial marker was placed close to the center of the target prior to the simulation. Amplitude based sorting was used in the scan. Eight or sixteen phases of reconstructed CT sets (depends on breathing pattern) can be sent to Velocity to create the maximum intensity projection (MIP) image set. Target ITV and fiducial ITV were drawn based on the MIP image. In patient localization, a 4D scan was taken with the same settings as the sim scan. Images were registered to match fiducial ITVs. Results: Ten liver cancer patients treated for 50Gy over 5 fractions, with amplitudes of breathing motion ranging from 4.3–14.5 mm, were analyzed in this study. Results show that the Intra & inter fraction variability in liver motion amplitude significantly less than the baseline inter-fraction shifts in liver position. 90% of amplitude change is less than 3 mm. The differences in the D99 and D95 GTV dose coverage between the 4D CT-on-Rails and the CBCT plan were small (within 5%) for all the selected cases. However, the average PTV volume by using the 4D CT-on-Rails is 37% less than the CBCT PTV volume. Conclusion: Simulation and Registration using 4D CT-on-Rails provides accurate target localization and is unaffected by larger breathing amplitudes as seen with 3D CBCT image registration. Localization with 4D CT-on-Rails can significantly reduce the PTV volume with sufficient tumor

Purpose: Head and Neck cancer treatment with IMRT/VMAT has two choices: split-filed IMRT(SFI), in which the LAN is treated with a separate anterior field and the extended whole-field IMRT(WFI) in which LAN is included with the IMRT/VMAT field. This study shows that under the same dose limit criteria, choosing the technique becomes a critical issue if daily localization and immobilization altered the dose distribution. Methods: Nine common head-and-neck cancer cases were chosen to illustrate how the daily localization and immobilization uncertainties affect to choose between SFI and WFI. Both SFI and WFI at upper target coverage were generated with VMAT. For each case, the same planning criteria were applied to the target and critical structures; therefore, similar target coverage and dose falloff can be observed in both techniques. Thirty days of kV cone beam CT(CBCT) images on each case were also delineated with contralateral and ipsilateral target as well as larynx as critical structure. About 300 CBCT images with daily delivered doses were analyzed and compared in a form of dose-volume histograms. Results: While both plans for SFI and WFI with VMAT planning utilized and meet the criteria of D95>prescription dose and for not-involved larynx with mean dose

415 Background: Sarcopenia (Sp) or severe loss of muscle mass is a prognostic factor in cancer patients. We assessed the association between Sp and outcomes in borderline resectable or locally advanced/unresectable pancreatic cancer patients undergoing chemoradiation (CRT). Methods: We reviewed all patients who underwent CRT at an NCI-designated cancer center between 2007-2012. Patients with available pre-treatment imaging were included in the analysis. Sp was defined as a lumbar skeletal muscle area/height of < 55.4 cm2/m2 for males and < 38.9 cm2/m2for females. Sp was correlated to treatment toxicity, cause specific survival (CSS), and overall survival (OS). Analysis was performed using chi-square test for categorical variables and Mann-Whitney U test for continuous variables. Kaplan-Meier method and Cox regression was used for survival analysis. Results: A total of 86 patients met the inclusion criteria with 32 (37%) patients being sarcopenic. The median age was 70 (range 46-91) with a median follow-up of 14 months (3-68). The majority of patients were male (57%), had T3 disease (47%), or were borderline resectable (63%). Twenty nine (33.7%) patients underwent surgery. Sarcopenic patients were less likely to undergo surgery (p = 0.024) versus non-sarcopenic patients. Otherwise there was no difference in clinical or treatment factors. The 12-month actuarial OS for patients with and without Sp was 47.9% and 70.7%, respectively (p = 0.047). The 12-month actuarial CSS for patients with and without Sp was 48% and 76%, respectively (p = 0.007). On multivariable analysis, after controlling for T-stage, N-stage, resectability, gender, pre-treatment CA 19-9, and surgery, Sp was no longer associated with CSS (HR 0.284 95% CI 0.774-2.398) or OS (HR 1.077 95% CI 0.626-1.853). Surgery remained associated with CSS (HR 0.205 95% CI = 0.102-0.412) and OS (HR 0.187 95% CI 0.096-0.363). T-stage also remained associated with both CSS (HR 0.616 95% CI 0.410-0.925) and OS (HR 0.649 95% CI 0.440-0.957). Conclusions: The presence of Sp decreases the likelihood of undergoing curative surgery for pancreatic cancer. This may be another useful tool to identify poor prognosis patients.

111 Background: Level I evidence suggests local treatment results in improved survival as compared to androgen deprivation therapy (ADT) alone or watchful waiting for high risk prostate cancer (CaP), but contemporary trends in primary treatment for high risk CaP are poorly understood. Our aim is to examine local therapy utilization for patients with high risk CaP using a large national cancer registry. Methods: Using the National Cancer Database (NCDB), patients with clinically localized CaP meeting National Comprehensive Cancer Network high risk criteria were identified from 2004-2009. Men with node positive or metastatic disease were excluded. Adjusting for diagnosis year and demographic we examined the association between patient characteristics and local therapy, defined as radical prostatectomy (RP) or radiation (RT), in men with high risk CaP using logistic regression models. Results: A total of 132,369 men met inclusion criteria with 80% receiving local therapy and 12% receiving no treatment. There was a small but significant increase in local therapy utilization from 2004-2009 (79 to 81%, p70 years (OR 0.27, CI 0.23-0.30) or Charlson morbidity count > 2 (OR 0.43, CI 0.39-0.46) were less likely to receive local therapy. Further, men of African American race (OR 0.7, CI 0.67-0.74) and Medicare (OR 0.82, CI 0.77-0.87) or Medicaid (OR 0.6, 0.53-0.68) insurance were less likely to receive primary treatment than Caucasian patients or those with private insurance. Conclusions: In the NCDB, 80% of men presenting with clinically localized high risk CaP undergo local therapy as part of multimodality treatment or as monotherapy, with RP overtaking RT+ADT as the primary local treatment of choice. Furthermore, racial and insurance disparities in the receipt of primary treatment are still evident, providing targets for emerging CaP quality of care initiatives.

407 Background: Many studies have associated a R0 resection to have significantly improved survival compared with a R1 resection in PAC. Patients (pts) who undergo NACRT often go to surgery 4-8 weeks after the end of therapy, before the effects of NACRT can be fully manifested. The goal of this study is to evaluate if a positive SM (+SM) after NACRT has the same poor prognosis as a +SM after upfront surgery. Methods: After IRB approval, we retrospectively reviewed all cases of surgically resected PAC at a single institution from Dec 1996 to Jan 2014. Pts were stratified by receipt of NACRT as well as by SM status. We excluded pts treated with palliative intent, metastatic disease at presentation, death within 90 days of surgery, and biliary or ampullary tumors. The primary endpoint was overall survival (OS). We assessed the relationship between pt and tumor variables with treatment/margin combination using Chi-squared tests. OS was examined using Kaplan-Meier curves, and we tested association with treatment/margin using log-rank tests. Results: A total of 213 pts met inclusion criteria; 111 received upfront surgery (group I) with 94 (85%) receiving adjuvant chemotherapy or CRT and 102 received NACRT (group II) with either concurrent 5-fluorouracil (n=18) or gemcitabine (n=84). There were 31 pts with +SM in group I and 29 pts in group II. Pt demographics were balanced. There was more vessel involvement in group II (81%) at diagnosis than group I (11%) (p

455 Background: Systemic therapy is a critical part of the management of locally advanced pancreatic cancer (LAPC) due to the risk of distant failure. In the clinic, anecdotal evidence suggests that maintaining dose intensity of chemotherapy is more challenging after prior chemoradiotherapy (CRT). We thus evaluated whether treatment or patient factors limit the amount of systemic therapy received in LAPC patients receiving CRT. Methods: Following IRB approval, we retrospectively reviewed all patients diagnosed with LAPC undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of non-gemcitabine chemotherapy or chemotherapy prior to CRT. Patient and treatment factors were evaluated for their relationship to total gemcitabine dose received during CRT and within the first three months post-CRT. Statistical analysis was performed using regression models. Results: A total of 76 patients met the inclusion criteria with a median age of 69 (range 44-89) and a median follow-up of 13.2 months (range 3-68). The median gemcitabine dose received during CRT was 3,000 mg/m2 of a planned 3,600 mg/m2 and post-CRT was 5000 mg/m2 of a planned 9,000 mg/m2. Patients receiving a higher percentage of the desired chemotherapy dose during CRT received a lower percentage of desired chemotherapy dose post-CRT (p

This note presents a method that recalculates the coordinates of the isocentre for patients undergoing stereotactic radiotherapy to the brain with a relocatable head frame based on a pre-treatment CT scan. The method was evaluated by comparing initial stereotactic coordinates of the isocentre with the recalculated coordinates for eight single-fraction patients. These patients had the Brown–Roberts–Wells (BRW) frame fixed to the outer table of the skull, and therefore the coordinates of any anatomical point should be identical between the initial scan and the pre-treatment scan. The differences between the two sets of coordinates were attributed to errors in the method. The results showed that the systematic errors in the recalculated coordinates were less than 0.05 mm, and they were not statistically significant. The random errors (one standard deviation) were from 0.35 mm (lateral) to 0.58 mm (vertical). The average value of the combined 3D difference was 0.75 mm.

The purpose of this work is to investigate the accuracy of dose calculation of a commercial treatment planning system (Corvus, Normos Corp., Sewickley, PA). In this study, 30 prostate intensity-modulated radiotherapy (IMRT) treatment plans from the commercial treatment planning system were recalculated using the Monte Carlo method. Dose-volume histograms and isodose distributions were compared. Other quantities such as minimum dose to the target (D(min)), the dose received by 98% of the target volume (D98), dose at the isocentre (D(iso)), mean target dose (D(mean)) and the maximum critical structure dose (D(max)) were also evaluated based on our clinical criteria. For coplanar plans, the dose differences between Monte Carlo and the commercial treatment planning system with and without heterogeneity correction were not significant. The differences in the isocentre dose between the commercial treatment planning system and Monte Carlo simulations were less than 3% for all coplanar cases. The differences on D98 were less than 2% on average. The differences in the mean dose to the target between the commercial system and Monte Carlo results were within 3%. The differences in the maximum bladder dose were within 3% for most cases. The maximum dose differences for the rectum were less than 4% for all the cases. For non-coplanar plans, the difference in the minimum target dose between the treatment planning system and Monte Carlo calculations was up to 9% if the heterogeneity correction was not applied in Corvus. This was caused by the excessive attenuation of the non-coplanar beams by the femurs. When the heterogeneity correction was applied in Corvus, the differences were reduced significantly. These results suggest that heterogeneity correction should be used in dose calculation for prostate cancer with non-coplanar beam arrangements.

The purpose of this study is to evaluate the dosimetric accuracy of MRI-based treatment planning for prostate cancer using a commercial radiotherapy treatment planning system. Three-dimensional conformal plans for 15 prostate patients were generated using the AcQPlan system. For each patient, dose distributions were calculated using patient CT data with and without heterogeneity correction, and using patient MRI data without heterogeneity correction. MR images were post-processed using the gradient distortion correction (GDC) software. The distortion corrected MR images were fused to the corresponding CT for each patient for target and structure delineation. The femoral heads were delineated based on CT. Other anatomic structures relevant to the treatment (i.e., prostate, seminal vesicles, lymph notes, rectum and bladder) were delineated based on MRI. The external contours were drawn separately on CT and MRI. The same internal contours were used in the dose calculation using CT- and MRI-based geometries by directly transferring them between MRI and CT as needed. Treatment plans were evaluated based on maximum dose, isodose distributions and dose-volume histograms. The results confirm previous investigations that there is no clinically significant dose difference between CT-based prostate plans with and without heterogeneity correction. The difference in the target dose between CT- and MRI-based plans using homogeneous geometry was within 2.5%. Our results suggest that MRI-based treatment planning is suitable for radiotherapy of prostate cancer.

Purpose: To investigate optimal fractionations to achieve high tumor control probabilities (TCPs) while maintaining acceptable normal‐tissue complication probability (NTCP) using radiobiological models with new parameters derived from recent clinical data for hypofractionated liver‐ cancer patients. Methods and Materials: Biological parameters for the Marsden TCP model were derived from reported outcomes of a multi‐ institutional Phase I/II trial. TCP and NTCP (using the LKB model with Dawson's parameters) were calculated for 8 livercancer patients treated with different hypofractionation regimens. The correlation between tumor size, the normal liver volume receiving at least 15 Gy and NTCP were examined. Using the BioSuite software, we determined the range of fractionation regimens that achieve high TCP for 5% NTCP. Results: The TCP parameters for livertumors are: alpha= 0.217 Gy‐1, alpha spread is 0.067 Gy‐1, assuming alpha/beta = 10 Gy and 107 tumor clonogens cm‐3. For any given fractionation we have found that NTCP is not correlated with the absolute liver volume receiving at least 15Gy, nor with the dose received by the hottest 700‐cc of the normal liver; these constraints are widely used in liver hypofractionation treatment planning. Instead, the parameter which correlates best with NTCP is the percentage liver volume receiving at least 15Gy. For 5 of the 8 patients, no more than 3 fractions were required to achieve a TCP over 96%; for 2 patients TCP increased gradually with number of fractions (from 3 to 10) to 95.2% and 92.2% respectively. The remaining patient had a small liver and larger target volume which resulted in high NTCP for any fractionation. Conclusions: A range of different hypofractionated regimens from 3×12Gy to 5×12 Gy is found to ensure excellent outcomes. However, the commonly used dose‐volume metrics for normal liver do not correlate well with NTCP. A new metric is proposed in this study.

Purpose: The CyberKnife uses an online prediction model to track moving targets. The system works well if patients can breathe regularly. However, some patients cannot maintain a regular breathing pattern, which means a larger PTV margin is necessary for these patients to ensure sufficient CTV dose coverage. However, it is very difficult to predict a patient's breathing pattern in advance. The purpose of this study is to investigate a quick and easy way to adapt the treatment plan if extra margins are needed. Methods: Multiple algorithms have been developed to calculate the adjustment. Generally, if a larger target region requires coverage by the prescription dose, the size of the beams will be larger and they should move in a peripheral direction for a certain distance to avoid hot spots. Dose is recalculated and renormalized consistently after the adjustment. If the dose distribution of the new plan covers the new PTV with acceptable conformality and coverage, the plan will be used for treatment. Otherwise, more iterations of the adjustment are performed. Dose calculations are limited to a small region surrounding the target to reduce calculation time. Results: 5 clinical cases (3 lungs, 1 liver and 1 adrenal) have been tested in this study. The dose margin can be extended up to 10 mm without changing dose distributions around the target region dramatically. The average PTV coverage is 98.7% compared to 99.1% in the original plans and the average CI is 1.22, which is slightly less than the 1.24 in the original plans. Conclusions: Treatment margins can be sufficiently expanded resulting in satisfactory plan quality for patients with breathing irregularities.

Purpose: Oral tongue carcinoma is a highly curable cancertreated by radiation therapy and especially by interstitial brachytherapy. However, multiple hairpins, needles or hollow catheters are needed to be inserted into the tumor bed for both low‐dose‐rate (LDR) and high‐dose‐rate (HDR) interstitial radiotherapy. The whole insertion procedure is quite invasive and painful to the patient each time it is administered. Therefore, the main aim of this study is to investigate the potential use of Cyberknife in the treatment of oral tongue cancer, which would dramatically reduce unpleasant experiences associated with HDR/LDR treatments. Methods: Using CTimages of the patient treated with the HDR interstitial implant, a structure (GTV) was created out of the applicator. A special device will be used to immobilize the tongue during treatment. In CyberKnife treatment planning, the Xsight Spine tracking method was used for patient localization. A 2 mm margin in all directions was added to account for potential localization uncertainties. Subsequent planning is based on prescribing 2000 cGy in 5 fractions to the PTV. Results: The isodose line of 66% (20 Gy in 5 fractions) covers the outer boundary of the PTV in the CyberKnife plan. The conformity index is 1.26 with 98.76% of the target volume covered by the prescription line. The maximum dose inside PTV is 30.3 Gy while the HDR treatment delivers more than 40 Gy to more than 20% of the PTV. Only 3.4 cc of the right mandible receives more than 10 Gy. The maximum dose to left mandible is only 4.4 Gy. The total treatment time is about 18 min/fraction. Conclusions: It is shown that Cyberknife treatment can be a viable alternative to interstitial HDR treatments, which may greatly improve the patient care with tongue cancer.

Purpose: Maximum intensity projection (MIP) reconstructed 4D CT reflects the range of target motion and thus is generally used for internal target volume (ITV) definition in lung stereotactic body radiotherapytreatment planning. During treatment delivery, CBCT is used for image guidance by aligning the target in the CBCT within the MIP‐based ITV. This work investigates whether these two image modalities are equivalent in determining the range of the target motion. Methods: A ball‐shaped polystyrene phantom with built‐in cube and sphere was attached to a motor‐ driven platform, which simulates a sinusoidal movement with changeable motion amplitude and frequency. Target motion was simulated both one‐ and two‐dimensionally by adjusting the platform alignment angle with the patient superior‐inferior (S‐I) direction. The Varian on‐board Exact Arms kV CBCT system and the GE LightSpeed 4‐slice CT integrated with Respiratory Position Management 4DCT scanner were used to scan the phantom that moved with four motion periods and varying peak‐to‐peak amplitudes. MIP images were produced. The maximum dimensions of the moving objects visualized in the two sets of images were measured on axial, coronal, and sagital views and compared, respectively. Results: When the motion is along the S‐I direction, the measured dimensions along the right‐ left and AP directions agree with the objects' dimensions with small uncertainties. The measured dimension along the S‐I direction in the MIP and the CBCT differ by a maximum of 10.2%, with a larger uncertainty associated with CBCT‐based measurements. We also found that the measured dimensions and the centroid positions of each object do not change with motion period, but with motion amplitude. Conclusions: The measured maximum dimensions of the objects, which are not affected by the motion frequency but by motion amplitude, are comparable between the two image modalities. Therefore, in general, CBCT and MIP images are equivalent in determining target motion.

Purpose: To study the dosimetric difference resulted in using the pencil beam algorithm instead of Monte Carlo (MC) methods for tumors adjacent to the skull. Methods: We retrospectively calculated the dosimetric differences between RT and MC algorithms for brain tumors treated with CyberKnife located adjacent to the skull for 18 patients (total of 27 tumors). The median tumor sizes was 0.53-cc (range 0.018-cc to 26.2-cc). The absolute mean distance from the tumor to the skull was 2.11 mm (range - 17.0 mm to 9.2 mm). The dosimetric variables examined include the mean, maximum, and minimum doses to the target, the target coverage (TC) and conformality index. The MC calculation used the same MUs as the RT dose calculation without further normalization and 1% statistical uncertainty. The differences were analyzed by tumor size and distance from the skull. Results: The TC was generally reduced with the MC calculation (24 out of 27 cases). The average difference in TC between RT and MC was 3.3% (range 0.0% to 23.5%). When the TC was deemed unacceptable, the plans were re-normalized in order to increase the TC to 99%. This resulted in a 6.9% maximum change in the prescription isodose line. The maximum changes in the mean, maximum, and minimum doses were 5.4 %, 7.7%, and 8.4%, respectively, before re-normalization. When the TC was analyzed with regards to target size, it was found that the worst coverage occurred with the smaller targets (0.018-cc). When the TC was analyzed with regards to the distance to the skull, there was no correlation between proximity to the skull and TC between the RT and MC plans. Conclusions: For smaller targets (< 4.0-cc), MC should be used to re-evaluate the dose coverage after RT is used for the initial dose calculation in order to ensure target coverage.

Purpose: To verify the dose accuracy of photon MLC delivered electron fields for implementing energy-intensity modulated electron radiotherapy (MERT) on an Artiste linac. Methods: It was proposed to deliver MERT on an Artiste linac at a short SSD (60 cm) to reduce beam penumbra caused by electron scatters. An in-house developed Monte Carlo (MC)-based dose calculation/optimization planning code was used for treatment planning. Our previous study showed that the measured dose distribution of a breast plan showed good agreement with the calculations in low-medium dose regions while the differences in high dose regions were outstanding. A continuous work found that the discrepancy is mainly caused by improper modeling in MC for the single focused MLC in the Artiste which was simplified as double focused in the previous MC simulations. With this remodeled MLC in the calculations, an energy-intensity modulated electron plan using 6, 9, 12 and 15 MeV was generated for a breast treatment on a breast phantom at a 60 cm SSD and recalculated regarding a solid water phantom. For a test study, four of MLC segments (each with a different energy) generated in the plan were delivered to the phantom and a film measurement was performed at the depth of 2 cm. The measured 2D dose distribution was then compared with calculations. Results: For composite doses of the four segments, measured 2D dose distributions overall agree well with the calculations (3mm/3%) in most area. The separate measurement for a single MLC segment for each of energies also showed the consistence with the calculations. Conclusion: After remodeling MLC in the MC calculations, the measured dose distribution for a subset of MLC segments from a MERT plan showed good agreement. Further detailed verification for the full plan will be the work in the next step.

Purpose: The CyberKnife (CK) M6 Series introduced a mulitleaf collimator (MLC) beam for extending its capability to the conventional radiotherapy. This work is to investigate delivery efficiency of this system as compared to a standard Varian linac when treating hepatic lesions. Methods: Nine previously treated patients were divided into three groups with three patients in each. Group one: fractionated radiotherapy; Group two: SBRT-like treatments and Group three: fractionated radiotherapy targeting two PTVs. The clinically used plans were generated with the Eclipse treatment planning system (TPS). We re-planned these cases using a Mulitplan (MP) TPS for the CK M6 and normalized to the same PTV dose coverage. CK factors (CF) (defined as modulation scaling factor in this work), number of nodes (NN), number of MLC segments (NS) and beam delivery time (BT) with an estimated image interval of 60 seconds, were used for evaluation of delivery efficiency. Results: Generated plans from the MP and Eclipse TPS demonstrated the similar quality in terms of PTV confomality index, minimum and maximum PTV doses, and doses received by critical structures. Group one: CF ranged from 8.1 to 8.7, NN from 30 to 40, NS from 120 to 155 and BT from 20 to 23more » minutes; group two: CF from 4.7 to 8.5, NN from 15 to 19, NS from 82 to 141 and BT from 18 to 24 minutes; and group three: CF from 7.9 to 10, NN from 47 to 49, NS from 110 to 113 and BT from 20 to 22 minutes. Conclusions: Delivery time is longer for the CK M6 than for the Varian linac (7.8 to 13.7 minutes). Further investigation will be necessary to determine if a PTV reduction from the tracking feature will shorten the delivery time without decreasing plan quality.« less

50 Background: Multiple retrospective studies have investigated the association between body mass index (BMI) and biochemical failure (BF) after definitive external beam radiotherapy (EBRT) of localized prostate cancer (CaP) prior to the dose escalation era, with conflicting results. The purpose of this study is to determine whether increasing BMI is associated with CaP outcomes in patients treated with dose escalated radiotherapy. Methods: From 2000 to 2010, we identified 1,291 patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity modulated radiation therapy (IMRT). BMI was categorized using World Health Organization classification. Multivariable competing risk and Cox proportional hazards regression models were used to assess the risk of BF, distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM). BF was defined as prostate-specific antigen (PSA) greater than or equal to nadir + 2 ng/mL. Covariates included age, androgen deprivation therapy (ADT), pre-treatment PSA (iPSA), Gleason score, and T stage. For OM, self-reported history of diabetes, heart disease, and hypertension were included. Results: Of the 1,291 patients identified, there were 20% normal (BMI2), 47% overweight (BMI 25-29.9), 23% obese class I (BMI 30-34.9), 6% obese class II (BMI 35-39.9), and 4% obese class III (BMI >40). Median follow-up was 43.7 months (range 1.1-127) with median age of 68 (range 36 to 88). Median dose was 78 Gy (range 76-80) and 33% of patients received ADT. Increasing BMI was inversely associated with age (p

Purpose: This work investigates dosimetrically how beam margin (BM) affects characteristics of 3D conformal lungcancer stereotactic body radiotherapy(SBRT)treatment planning in terms of the conformality index (CI), high‐dose spillage and intermediate‐dose spillage. Method and Materials: Ten patient plans were generated in the Eclipse treatment planning system using the Anisotropic Analytical Algorithm (AAA) for BM of 0, 2 and 4 mm, respectively. All plans were normalized so that at least 95% of PTV receives the prescription dose and 99% of PTV receives at least 90% of the prescription dose. The high‐dose spillage was defined by the ratio of the volume of all tissue outside the PTV receiving a dose larger than 105% of the prescription dose to the PTV, and the intermediate‐dose spillage was evaluated by the mean dose at the 3mm shell distanced at 2 cm away from the PTV surface. Results: The CIs are much lower for 0 or 2 mm BM than those of 4 mm BM for all patient plans while for two patients, slightly higher for 0 mm BM than those for 2 BM. The high‐dose spillages were on average about 7% lower for 0 or 2 mm BM than those of 4 mm BM for all patient plans while for three patients, higher for 0 mm BM than those of 2 mm BM. The intermediate‐dose spillages were lower for 0 or 2mm BM than those of 4 mm BM. Conclusion: With assumption that PTV fully covers the microscopic disease, tumor motion and setup uncertainty, and following recent ASTRO/ACR guideline that every effort should be made to minimize the volume of surrounding normal tissues exposed to high dose levels, 3D conformal lungcancerSBRT plans appear superior with 2 mm BM or less depending on the tumor location, size and patient geometry.

Purpose: To assess the target relocalization accuracy in respect to the bony structures using daily CBCT and thus to validate the planning target volume (PTV) margin used in the lungSBRT.Methods and Materials: All patients underwent 4D CT scanning in preparation for lungSBRT. The internal target volume (ITV) is outlined from the reconstructed 4D data using the maximum‐intensity projection (MIP) algorithm. The clinical target volume (CTV) is defined as the ITV plus 3 mm margin and an additional 3 mm margin is added to the CTV to make the PTV. Conformal treatment planning is performed on the helical images, to which the MIP images were fused. Prior to each treatment, CBCT is used to align with the simulation CT (helical) based on bony anatomy. The necessary shifts are recorded. The treating physician then checks and modifies the alignment based on target relocalization within the PTV (soft tissue alignment). The final shifts are derived based on the soft tissue alignment. Two sets of shifts are compared here for the purpose of the study. Results: For 8 consecutive patients, treating 9 targets for a total of 36 fractions, it was found that the treatment setup errors (based on bony anatomy alignment) are 0.23±0.47 cm in the anterior‐posterior (AP), 0.06±0.5 cm in the lateral (Lat), and 0.18±0.39 cm in the superior‐inferior (S‐I) directions, respectively. After the setup error correction, the targets were found to be within the PTV margin with the average shifts of 0.064±0.64 cm in AP, 0.089±0.41 cm in Lat, and 0.21±0.38 cm in S‐I directions, respectively. Conclusions: For this patient population, the target relocation accuracy is generally satisfactory after patient setup error correction. This demonstrates that the PTV margin designed based on the ITV outlined on MIP images is appropriate to account for intra and inter‐fractional tumor motions.