Purpose/Background We analyzed the predictive value of non-x-ray voxel Monte Carlo (XVMC)-based modeling of tumor control probability (TCP) and normal tissue complication probability (NTCP) in patients treated with stereotactic body radiotherapy (SBRT) using the XVMC dose calculation algorithm. Materials/Methods We conducted an IRB-approved retrospective analysis in patients with lung tumors treated with XVMC-based lung SBRT. For TCP, we utilized tumor size-adjusted biological effective dose (s-BED) TCP modeling validated in non-MC dose calculated SBRT to: (1) verify modeling as a function of s-BED in patients treated with XVMC-based SBRT; and (2) evaluate the predictive potential of different PTV dosimetric parameters (mean dose, minimum dose, max dose, prescription dose, D95, D98, and D99) for incorporation into the TCP model. Correlation between observed local control and TCPs was assessed by Pearson's correlation coefficient. For NTCP, Lyman NTCP Model was utilized to predict grade 2 pneumonitis and rib fracture. Results Eighty-four patients with 109 lung tumors were treated with XVMC-based SBRT to total doses of 40 to 60 Gy in 3 to 5 fractions. Median follow-up was 17 months. The 2-year local and local-regional control rates were 91% and and 78%, respectievly. All estimated TCPs correlated significantly with 2-year actuarial local control rates (P < 0.05). Significant corelations between TCPs and tumor control rate according to PTV dosimetric parameters were observed. D99 parameterization demonstrated the most robust correlation between observed and predicted tumor control. The incidences of grade 2 pneumonitis and rib fracture vs. predicted were 1% vs. 3% and 10% vs. 13%, respectively. Conclusion Our TCP results using a XVMC-based dose calculation algorithm are encouraging and yield validation to previously described TCP models using non-XVMC dose methods. Furthermore, D99 as potential predictive parameter in the TCP model demonstrated better correlation with clinical outcome.

The main objectives of this retrospective analysis were to examine and compare with our clinical observations the predictive power of size-adjusted tumor control probability (TCP) model for 2-yr local control rates and the Lyman Normal Tissue Complication Probability (NTCP) model for rib fracture rates in the treatment of peripherally located NSCLC lesions using X-ray Voxel Monte Carlo (XVMC) based SBRT dose algorithms. We retrospectively analyzed 21 patients with Stage I-II peripherally located NSCLC who had been treated with XVMC-based dose algorithms per RTOG 0915 guidelines. Each plan was normalized to deliver 50-60 Gy to PTV in 3-5 fractions (PTV D100 = 95%). ITV was extracted from MaxIP images of 4D-CT scans and PTV included ITV plus a 5 mm margin. Organ-at-risks, including ribs were contoured on MeanIP images of 4D-CT scans. For TCP, we utilized previously defined size-adjusted biological effective dose (s-BED) modelling: TCP = EXP[sBED-TCD50]/k÷ (1.0 + EXP[sBED-TCD50]/k), where k = 31 Gy corresponding to TCD50 = 0 Gy and s-BED is BED 10 minus 10 times the tumor diameter [Ohri et al, IJROBP, 2012]. We adopted this s-BED model using more realistic XVMC-computed dose to 99% of PTV (PTV D99) as a predictive parameter for 2-yr local control rate. Normal rib DVH and α/β = 3 Gy were used to predict rib fracture in the parameterized Lyman NTCP model and compared with our clinical observations. Kaplan Meier curves were generated with GraphPad Prism 6.0 software to estimate 2-yr observed local control rates for comparison to those predicted by the TCP model. Median follow-up was 11 months. Average PTV diameter was 4.2 cm (range = 2.8 - 6.7 cm). The predicted and clinically observed 2-year actuarial local control rates were 86.6% (±8%) and 95.0%, respectively. With NTCP model parameters, our average predicted rib fracture rate was 12.6% (±8.5%) and observed rib fracture rate was 9.5%. Rib fractures occurred in two patients who received higher maximum average point doses (∼72 Gy) and average dose to 1 cc of rib (∼65 Gy). Both had 4.3 cm and 4.1 cm sized lesions which were embedded in the chest wall and tumor control was achieved with 60 Gy in 5 fractions. In our group of NSCLC patients treated with XVMC-based SBRT per RTOG 0915 guidelines, the size adjusted TCP model demonstrated excellent predictive potential for 2-yr actuarial local control rates. The predicted rib fracture rate was comparable to our clinical observations. Based upon these results, it appears that maximum rib dose, dose to 1cc of the rib, and proximity of target to chest wall play the largest role in predicting chest wall toxicity. Clinical application of these parametric values/models may potentially allow for target dose escalation and/or reduction in chest wall toxicity. Further validation of these radiobiological models with large cohort of Monte Carlo-based lung SBRT patients is warranted.

To describe radiographic evidence of radiation pneumonitis (rRP) and fibrosis (rRF) and determine what dosimetric parameters correlate with rRP and rRF after stereotactic ablative radiation therapy (SABR) to the lung.

e16620 Background: A phase I-II trial was conducted to determine the safety and feasibility of post-prostatectomy radiation therapy (RT), concurrent docetaxel and hormonal therapy (HT) in patients with high risk pathologic (p) T2-3N0M0 prostate cancer. Methods: Post-prostatectomy high risk prostate cancer was defined as non-metastatic disease with either an undetectable, persistent or rising PSA with 1 or more of the following features: (1) pT2-T3aN0 disease, positive or negative margins, with either (a) a gleason score (GS) of ≥ 8, and/or (b) a PSA doubling time of ≤ 10 months, and/or (c) with a pre-RT PSA of ≥ 1.0 ng/ml; and/or (2) pT3bN0 disease. The tri-modality treatment consisted of 6 months of HT [Casodex (50 mg po daily), and Lupron (22.5 mg im q 3 mos x 2)], RT to 66.0 Gy at 2.0 Gy/fraction (fx) once daily, and concurrent weekly docetaxel at 20 mg/m2 x 7 infusions. Results: Between October 2008 and July 2014, a total of 32 patients were enrolled. The clinical and disease characteristics of the 32 patients were as follows: Median age, years (range) = 64 (44 - 74); pathologic T-stage was as follows: pT2a = 2 patients, pT2c = 5, pT3a = 13 and pT3b = 12. 9 were in the adjuvant group while 23 patients were in the salvage category. One of the 32 patients withdrew consent shortly after receiving one injection of Lupron due to “hot flashes” but before starting his chemoradiation therapy treatments. Among the other 31 patients, all have completed their trimodality therapy. All of these 31 patients completed their full dose of RT (66 Gy). These 31 patients also received a median of 7 weekly docetaxel infusions (range = 5 - 8). Only 3 of these 31 patients experienced acute grade 3 diarrhea during the chemoradiation therapy, which was diet related in 1 patient. Among the other 2 patients who experienced grade 3 diarrhea, one was using excessive stool softners due to constipation, and the other patient was using excessive laxatives / prune juice. There have been no acute grade ≥ 3 GU toxicity. Conclusions: Theresults of our completed phase I-II clinical trial indicate that our post-prostatectomy tri-modality therapy is well tolerated with a very high feasibility rate in patients with high risk pT2-3N0M0 prostate cancer. Clinical trial information: NCT00669162.

The purpose of the study was to evaluate Monte Carlo-generated dose distributions with the X-ray Voxel Monte Carlo (XVMC) algorithm in the treatment of peripheral lung cancer patients using stereotactic body radiotherapy (SBRT) with non-protocol dose-volume normalization and to assess plan outcomes utilizing RTOG 0915 dosimetric compliance criteria. The Radiation Therapy Oncology Group (RTOG) protocols for non-small cell lung cancer (NSCLC) currently require radiation dose to be calculated using tissue density heterogeneity corrections. Dosimetric criteria of RTOG 0915 were established based on superposition/convolution or heterogeneities corrected pencil beam (PB-hete) algorithms for dose calculations. Clinically, more accurate Monte Carlo (MC)-based algorithms are now routinely used for lung stereotactic body radiotherapy (SBRT) dose calculations. Hence, it is important to determine whether MC calculations in the delivery of lung SBRT can achieve RTOG standards. In this report, we evaluate iPlan generated MC plans for peripheral lung cancer patients treated with SBRT using dose-volume histogram (DVH) normalization to determine if the RTOG 0915 compliance criteria can be met. This study evaluated 20 Stage I-II NSCLC patients with peripherally located lung tumors, who underwent MC-based SBRT with heterogeneity correction using X-ray Voxel Monte Carlo (XVMC) algorithm (Brainlab iPlan version 4.1.2). Total dose of 50 to 54 Gy in 3 to 5 fractions was delivered to the planning target vol-ume (PTV) with at least 95% of the PTV receiving 100% of the prescription dose (V100% ≥ 95%). The internal target volume (ITV) was delineated on maximum intensity projection (MIP) images of 4D CT scans. The PTV included the ITV plus 5 mm uniform margin applied to the ITV. The PTV ranged from 11.1 to 163.0 cc (mean = 46.1 ± 38.7 cc). Organs at risk (OARs) including ribs were delineated on mean intensity projection (MeanIP) images of 4D CT scans. Optimal clinical MC SBRT plans were generated using a combination of 3D noncoplanar conformal arcs and nonopposing static beams for the Novalis-TX linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5 mm leaf width at isocenter) and 6 MV-SRS (1000 MU/min) beam. All treatment plans were evaluated using the RTOG 0915 high- and intermediate-dose spillage criteria: conformity index (R100%), ratio of 50% isodose volume to the PTV (R50%), maximum dose 2 cm away from PTV in any direction (D2cm), and percent of normal lung receiving 20Gy (V20) or more. Other OAR doses were documented, including the volume of normal lung receiving 5 Gy (V5) or more, dose to < 0.35 cc of spinal cord, and dose to 1000 cc of total normal lung tissue. The dose to < 1 cc, < 5 cc, < 10 cc of ribs, as well as maximum point dose as a function of PTV, prescription dose, and a 3D distance from the tumor isocenter to the proximity of the rib contour were also examined. The biological effective dose (BED) with α/β ratio of 3 Gy for ribs was analyzed. All 20 patients either fully met or were within the minor deviation dosimetric compliance criteria of RTOG 0915 while using DVH normalization. However, only 5 of the 20 patients fully met all the criteria. Ten of 20 patients had minor deviations in R100% (mean = 1.25 ± 0.09), 13 in R50% (mean = 4.5 ± 0.6), and 11 in D2cm (mean = 61.9 ± 8.5). Lung V20, dose to 1000 cc of normal lung, and dose to < 0.35 cc of spinal cord were met in accordance with RTOG criteria in 95%, 100%, and 100%, respectively, with exception of one patient who exhibited the largest PTV (163 cc) and experienced a minor deviation in lung V20 (mean = 4.7±3.4%). The 3D distance from the tumor isocenter to the proximal rib contour strongly correlated with maximum rib dose. The average values of BED3Gy for maximum point dose and dose to < 1 cc of ribs were higher by a factor of 1.5 using XVMC compared to RTOG 0915 guidelines. The preliminary results for our iPlan XVMC dose analyses indicate that the majority (i.e., 75% of patient population) of our patients had minor deviations when compared to the dosimetric guidelines set by RTOG 0915 protocol. When using an exclusively sophisticated XVMC algorithm and DVH normalization, the RTOG 0915 dosimetric compliance criteria such as R100%, R50%, and D2cm may need to be revised. On average, about 7% for R100%, 13% for R50%, and 14% for D2cm corrections from the mean values were necessary to pass the RTOG 0915 compliance criteria. Another option includes rescaling of the prescription dose. No further adjustment is necessary for OAR dose tolerances including normal lung V20 and total normal lung 1000 cc. Since all the clinical MC plans were generated without compromising the target coverage, rib dose was on the higher side of the protocol guidelines. As expected, larger tumor size and proximity to ribs correlated to higher absolute dose to ribs. These patients will be clinically followed to determine whether delivered MC-computed dose to PTV and the ribs dose correlate with tumor control and severe chest wall pain and/or rib fractures. In order to establish new specific MC-based dose parameters, further dosimetric studies with a large cohort of MC lung SBRT patients will need to be conducted.

A prospective clinical trial, Radiation Therapy Oncology Group (RTOG) 0933, has demonstrated that whole brain radiotherapy (WBRT) using conformal radiation delivery technique with hippocampal avoidance is associated with less memory complications. Further sparing of other organs at risk (OARs) including the scalp, ear canals, cochleae, and parotid glands could be associated with reductions in additional toxicities for patients treated with WBRT. We investigated the feasibility of WBRT using volumetric-modulated arc therapy (VMAT) to spare the hippocampi and the aforementioned OARs. Ten patients previously treated with nonconformal WBRT (NC-WBRT) using opposed lateral beams were retrospectively re-planned using VMAT with hippocampal sparing according to the RTOG 0933 protocol. The OARs (scalp, auditory canals, cochleae, and parotid glands) were considered as dose-constrained structures. VMAT plans were generated for a prescription dose of 30 Gy in 10 fractions. Comparison of the dosimetric parameters achieved by VMAT and NC-WBRT plans was performed using paired t-tests using upper bound p-value of < 0.001. Average beam on time and monitor units (MUs) delivered to the patients on VMAT were compared with those obtained with NC-WBRT. All VMAT plans met RTOG 0933 dosimetric criteria including the dose to hippocampi of 100% of the volume (D100%) of 8.4 ± 0.3 Gy and maximum dose of 15.6 ± 0.4 Gy, respectively. A statistically significant dose reduction (p < 0.001) to all OARs was achieved. The mean and maximum scalp doses were reduced by an average of 9 Gy (32%) and 2 Gy (6%), respectively. The mean and maximum doses to the auditory canals were reduced from 29.5 ± 0.5 Gy and 31.0 ± 0.4 Gy with NC-WBRT, to 21.8 ± 1.6 Gy (26%) and 27.4 ± 1.4 Gy (12%) with VMAT. VMAT also reduced mean and maximum doses to the cochlea by an average of 4 Gy (13%) and 2 Gy (6%), respectively. The parotid glands mean and maximum doses with VMAT were 4.4 ± 1.9 Gy and 15.7 ± 5.0 Gy, compared to 12.8 ± 4.9 Gy and 30.6 ± 0.5 Gy with NC-WBRT, respectively. The average dose reduction of mean and maximum of parotid glands from VMAT were 65% and 50%, respectively. The average beam on time and MUs were 2.3minutes and 719 on VMAT, and 0.7 minutes and 350 on NC-WBRT. This study demonstrated the feasibility of WBRT using VMAT to not only spare the hippocampi, but also significantly reduce dose to OARs. These advantages of VMAT could potentially decrease the toxicities associated with NC-WBRT and improve patients' quality of life, especially for patients with favorable prognosis receiving WBRT or patients receiving prophylactic cranial irradiation (PCI).

Purpose 11C-acetate positron emission tomography (PET) imaging allows for the detection of occult metastatic disease that may otherwise go undetected with standard imaging for prostate cancer (PCa). The aim of this study was to evaluate lymph node coverage of the standard Radiation Therapy Oncology Group (RTOG) whole pelvic radiation therapy (WPRT) field in patients found to have node-positive PCa determined by 11C-acetate PET imaging. Methods and materials A retrospective analysis was conducted on 125 PCa patients who underwent 11C-acetate PET scans at our institution between 2007 and 2014. Patients were included if they had evidence of nodal disease without distant metastatic cancer. Individual lymph nodes were characterized by location, size, and relationship to the RTOG WPRT field. Results A total of 55 11C-acetate PET scans (from 54 men) met criteria for inclusion in the study. Median age at diagnosis was 61 years. Median prostate-specific antigen values at diagnosis and at the time of the scan were 9.2 and 8.1 ng/mL, respectively. A total of 159 positive lymph nodes were identified, 78% of which were smaller than 1 cm. The most frequently involved lymphatic regions were the external iliacs (38.4%), para-aortics (19.5%), and common iliacs (16.3%). Additionally, 10.1% of positive nodes were identified as nodes of Cloquet. Of the positive nodes, 51.6% were determined to reside outside of the radiation field and, of those, the most common sites were para-aortic (36.9%), proximal common iliac (17.8%), distal external iliac (17.8%), and nodes of Cloquet (17.8%). Conclusions Based on 11C-acetate PET imaging in patients with PCa, the standard RTOG WPRT field may miss more than one-half of all positive lymph nodes. Clinicians should be aware of the potential for insufficient nodal coverage when using the standard RTOG WPRT field in patients with node-positive PCa. 11C-acetate PET imaging may be useful in defining target volumes for these patients.

The purpose of this study was to retrospectively investigate the accuracy, plan quality, and efficiency of using intensity-modulated arc therapy (IMAT) for whole brain radiotherapy (WBRT) patients with sparing not only the hippocampus (following RTOG 0933 compliance criteria) but also other organs at risk (OARs). A total of 10 patients previously treated with nonconformal opposed laterals whole-brain radiotherapy (NC-WBRT) were retrospectively replanned for hippocampal sparing using IMAT treatment planning. The hippocampus was volumetrically contoured on fused diagnostic T1-weighted MRI with planning CT images and hippocampus avoidance zone (HAZ) was generated using a 5 mm uniform margin around the hippocampus. Both hippocampi were defined as one paired organ. Whole brain tissue minus HAZ was defined as the whole-brain planning target volume (WB-PTV). Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis TX linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5 mm leaf width at isocenter) and 6 MV beam for a prescription dose of 30 Gy in 10 fractions following RTOG 0933 dosimetric criteria. Two full coplanar arcs with orbits avoidance sectors were used. In addition to RTOG criteria, doses to other organs at risk (OARs), such as parotid glands, cochlea, external/middle ear canals, skin, scalp, optic pathways, brainstem, and eyes/lens, were also evaluated. Subsequently, dose delivery efficiency and accuracy of each IMAT plan was assessed by delivering quality assurance (QA) plans with a MapCHECK device, recording actual beam-on time and measuring planed vs. measured dose agreement using a gamma index. On IMAT plans, following RTOG 0933 dosimetric criteria, the maximum dose to WB-PTV, mean WB-PTV D2%, and mean WB-PTV D98% were 34.9 ± 0.3 Gy, 33.2 ± 0.4 Gy, and 26.0± 0.4Gy, respectively. Accordingly, WB-PTV received the prescription dose of 30Gy and mean V30 was 90.5% ± 0.5%. The D100%, and mean and maximum doses to hippocampus were 8.4 ± 0.3 Gy, 11.2 ± 0.3 Gy, and 15.6 ± 0.4 Gy, on average, respectively. The mean values of homogeneity index (HI) and conformity index (CI) were 0.23 ± 0.02 and 0.96 ± 0.02, respectively. The maximum point dose to WB-PTV was 35.3 Gy, well below the optic pathway tolerance of 37.5 Gy. In addition, compared to NC-WBRT, dose reduction of mean and maximum of parotid glands from IMAT were 65% and 50%, respectively. Ear canals mean and maximum doses were reduced by 26% and 12%, and mean and maximum scalp doses were reduced by 9 Gy (32%) and 2 Gy (6%), on average, respectively. The mean dose to skin was 9.7 Gy with IMAT plans compared to 16 Gy with conventional NC-WBRT, demonstrating that absolute reduction of skin dose by a factor of 2. The mean values of the total number of monitor units (MUs) and actual beam on time were 719 ± 44 and 2.34 ± 0.14 min, respectively. The accuracy of IMAT QA plan delivery was (98.1 ± 0.8) %, on average, with a 3%/3 mm gamma index passing rate criteria. All of these plans were considered clinically acceptable per RTOG 0933 criteria. IMAT planning provided highly conformal and homogenous plan with a fast and effective treatment option for WBRT patients, sparing not only hippocampi but also other OARs, which could potentially result in an additional improvement of the quality life (QoL). In the future, we plan to evaluate the clinical potential of IMAT planning and treatment option with hippocampal and other OARs avoidance in our patient's cohort and asses the QoL of the WBRT patients, as well as simultaneous integrated boost (SIB) for the brain metastases diseases.

We retrospectively investigated the accuracy, quality and efficiency of using VMAT for the treatment planning of WBRT with hippocampal sparing following RTOG 0933 compliance criteria. Ten patients previously treated with non-conformal opposed laterals (NC-WBRT) were retrospectively re-planned for hippocampal sparing using VMAT planning. The hippocampus was volumetrically contoured on fused T1-weighted MRI with planning CT images and hippocampus avoidance zone (HAZ) was generated using a 5 mm uniform margin around the hippocampus. Whole brain tissue minus HAZ was defined as the whole brain planning target volume (WB-PTV). Highly conformal VMAT plans were generated for a prescription dose of 30 Gy in 10 fractions per RTOG 0933 criteria. Two full coplanar arcs with eyes avoidance sectors were used. In addition, doses to other organs at risk (OARs) such as parotid glands, ear canals, scalp etc. were also evaluated. Subsequently, dose delivery efficiency and accuracy of each VMAT plan was assessed by delivering quality assurance (QA) plans with a MapCHECK device, recording beam on time and measuring plan vs. measured dose agreement using a gamma index. The maximum dose to WB-PTV, mean WB-PTV D2%, and mean WB-PTV D98% were 34.9 ± 0.3 Gy, 33.2 ± 0.4 Gy, and 26.0 ± 0.4 Gy respectively. WB-PTV received the prescription dose of 30 Gy and mean V30 was 90.5 ± 0.5%. The D100%, mean and maximum doses to hippocampus were 8.4 ± 0.3 Gy, 11.2 ± 0.3 Gy and 15.6 ± 0.3 Gy, on average, respectively. Mean values of homogeneity index (HI) and conformity index (CI) were 0.23 ± 0.02 and 0.96 ±0.02, respectively. The maximum point dose to WB-PTV was 35.3 Gy, well below the optic pathway tolerance of 37.5Gy. Compared to NC-WBRT, dose reduction of mean and max of parotid glands from VMAT were 65% and 50%, respectively. Ear canals mean and max doses were reduced by 26% and 12%, and mean and maximal scalp doses were reduced by 9 Gy (32%) and 2 Gy (6%), on average, respectively. The mean values of the total number of monitor units (MUs) and actual beam on time were (719 ± 44) and (2.3 ± 0.1) min, respectively. The accuracy of RA QA plan delivery was 98.1 ± 0.8%, on average, with a 3%/3 mm gamma index passing rate criteria. All VMAT plans met the RTOG compliance criteria for WBRT, hippocampi, optic chiasm/nerve constraints. VMAT provided highly conformal and homogenous plans with an accurate and efficient option for WBRT with hippocampal sparing. VMAT planning used less MUs and required less beam on time than traditional IMRT based planning for WBRT with hippocampal sparing. VMAT also significantly reduce doses to other OARs compared to NC-WBRT. We plan to test our VMAT WBRT hippocampal sparing treatment approach in a larger group of patients to further validate these retrospective results including reduction of radiation dose to OARs as well as explore the clinical potential of concurrent boost.

VMAT offers, versus intensity modulated radiation therapy (IMRT), fewer monitor units, faster delivery and conformal dose distributions for complex head & neck (H&N) plans. Optimal grid size is a consideration given non uniform fluence utilized in VMAT/IMRT. Aim of this study is to compare important dose volume histogram (DVH) parameters using various dose calculation grid sizes and angular resolution for H&N plans using VMAT technique. Five H&N patients with simultaneous integrated boost (SIB) prescriptions treated using VMAT technique with 6MV photon were chosen. Doses were recomputed using grid sizes of 1, 2, 3, 4, 5mm and angular resolutions of 1, 2 and 5o. Forty five plans were computed; 9 plans for each patient. 70Gy in 33 fractions was prescribed to cover 95% of high risk PTV, 60Gy and 54Gy was prescribed to intermediate and low risk PTVs, respectively. Two full arcs were used for VMAT planning. Dosimetric parameters such as total Monitor Units(MUs), max, min, mean doses and ICRU-83 parameters such as D98%, D50%, and D2% were analyzed. Max, mean and 1cc volume doses were analyzed for critical structures such as spinal cord, brainstem, parotids, mandible and cochlea. Conformity index were also analyzed and compared for different grid sizes. All values were compared to the 1mm and 1o resolution values. As grid size increases from 2 to 5mm, MUs to deliver same prescribed dose increase. Up to 3% higher MUs were required for 5mm grid; however, no change in MUs for 2mm grid size was observed. Changing the angular increment did not change MUs for the same grid size. PTV max dose deviations were within 1% for all grid sizes and angular resolution. PTV min doses were lower up to 7% for 5mm grid size. PTV mean dose were higher up to 2% for 5mm grid size for others they were within 1%. PTV D98% varied ±2% for 4 to 5mm grids. PTVs D2% were higher up to 3% for 5mm grid. PTVs D50% were higher up to 2% for 5mm grid. Max dose to spinal cord and D1cc varies up to 3% as grid size increases. Brainstem max and D1cc doses were also higher up to 7% and 3% respectively as grid size increased from 2 to 5mm.Madible max dose and D1cc varied ±2% and ±3% respectively. Parotids mean dose and D50% were higher up to 4% and 8% respectively for higher grid. Cochlea mean dose was higher from 3 to 31% for varying grid size from 2 to 5mm. Impact of angular increment for the same grid size was insignificant (<1%) for PTVs and critical structures. Varying the angular resolution did not affect the dose to either PTV or critical structures significantly. In this study we observed that effect of grid size >2mm becomes clinically significant for smaller structures and at higher dose gradient for H&N VMAT. Since MUs and dose to PTVs and critical structures change with varying calculation grid size, it is recommended that the smallest grid size be utilized for accurate dose calculations, preferably ≤2mm for H&N VMAT plans.

PURPOSE:Prostate specific antigen screening has led to the early detection of prostate cancer. However, there has also been concern about the over diagnosis and overtreatment of patients with indolent cancers. We performed a population based analysis to evaluate the trade-off between excess treatment and prevention. MATERIALS AND METHODS:We used the CDC (Centers for Disease Control and Prevention) Behavioral Risk Factor Surveillance System survey from 2001 to 2010 to determine rates of prostate specific antigen screening. We used the SEER database to identify all patients diagnosed with prostate cancer from 1988 (pre-prostate specific antigen screening) to 2010. Demographic, staging and treatment data were collected. Cases were classified as early (low/intermediate risk), high risk, node positive or metastatic disease. RESULTS:Prostate specific antigen screening rates in the last 2 years were 54% for men older than 40 years, including 71% for those older than 60, and did not vary during 2001 to 2010. Comparing 1988 and 2000 to 2010, per 100,000 men the incidence of early prostate cancer increased (61.7 to 113.7), while high risk cancer increased (20.7 to 28.2), node positive cancer decreased (3.7 to 1.8) and metastatic cancer decreased (13.6 to 6.2). The rate of definitive primary treatment (radical prostatectomy or radiation therapy) for men with early cancer increased from 47% to 67% (p <0.001). CONCLUSIONS:Prostate specific antigen screening has led to an additional diagnosis of 5.8 cases of early stage cancer and 3.9 cases receiving treatment for early cancer for every 1 less case of stage IV disease at initial diagnosis. This ratio represents the worst-case scenario for overtreatment and provides a quantitative basis for studying the effect of prostate specific antigen screening.

Radiation Therapy Oncology Group (RTOG) protocols for NSCLC currently require radiation doses calculated using tissue density heterogeneity corrections. Dosimetric criteria for RTOG 0915 were established using superposition/convolution algorithm for dose calculations. Clinically, more accurate MC-based algorithms are now routinely used for lung SBRT; hence, we compared x-ray voxel MC (XVMC) algorithm to the non-MC algorithm based dosimetric criteria used in RTOG protocol 0915 for the calculation of SBRT doses in the treatment of peripheral NSCLC lesions. Twenty patients with stage I-II peripheral NSCLC lesions were treated with SBRT using the heterogeneity corrected XVMC algorithm on a linear accelerator. These patients were treated to total doses of 54–50 Gy in 3–5 fractions delivered to planning target volume (PTV) with at least PTV (V100%) = 95%. Internal target volume (ITV) was delineated on maximum intensity projection (MIP) images of 4D CT scans. Planning target volume included ITV plus 5 mm uniform margin; PTV volumes ranged from 11.1 to 163.0 cm3 (mean = 46.1 ± 38.7 cm3). Organs-at-risk (OARs) were delineated on MeanIP images of 4D CT scans. Optimal clinical SBRT plans were generated using a combination of 3D non-coplanar conformal arcs/static beams consisting of high-definition, multi-leaf collimators and 6MV-SRS (1000 MU/min) beam. Treatment plans were evaluated using RTOG 0915 criteria: conformity index (R100%), ratio of 50% isodose volume to the PTV (R50%), maximum dose 2 cm away from PTV in any direction (D2 cm), and lung V20. Organ-at-risk doses were documented, including dose to <0.35 cm3 of the spinal cord, dose to 1000 cm3 of normal lung and max and 1 cm3 doses to rib. All 20 patients either fully met or were within the minor deviation dosimetric compliance criteria of RTOG 0915; however, only 5 of the 20 patients fully met all the criteria. Ten of twenty patients had minor deviations in R100% (mean = 1.25 ± 0.09), thirteen in R50% (mean = 4.5 ± 0.6), and eleven in D2 cm (mean = 61.9 ± 8.5). Lung V20, dose to 1000 cm3 of normal lung and dose to <0.35 cm3 of spinal cord were met in accordance with RTOG criteria in 95%, 100%, and 100%, respectively, except, one patient who had the largest PTV (163 cm3) had minor deviation in lung, V20 (mean = 4.7 ± 3.4%). Rib doses were higher (up to 15%, on average) than protocol guidelines. Our preliminary results using the XVMC algorithm for SBRT dose calculations in the treatment of peripheral NSCLC lesions indicate that only 25% of the patients fully met the RTOG criteria. Recognizing that the MC based algorithms are more accurate, the RTOG 0915 criteria such as R100%, R50%, and D2 cm for lung SBRT may need to be revised. In general, about 7% for R100%, 13% for R50%, and 14% for D2 cm corrections could be applied. These patients will be followed up to evaluate the rib toxicity; also, the MC-based algorithms for lung SBRT dose calculations are highly recommended.

Purpose:Skin dose can be the limiting factor and fairly common reason to interrupt the treatment, especially for treating head‐and‐neck with Intensity‐modulated‐radiation‐therapy(IMRT) or Volumetrically‐modulated ‐ arc‐therapy (VMAT) and breast with tangentially‐directed‐beams. Aim of this study was to investigate accuracy of near‐surface dose predicted by Eclipse treatment‐planning‐system (TPS) using Anisotropic‐Analytic Algorithm (AAA)with varying calculation grid‐size and comparing with metal‐oxide‐semiconductor‐field‐effect‐transistors(MOSFETs)measurements for a range of clinical‐conditions (open‐field,dynamic‐wedge, physical‐wedge, IMRT,VMAT).Methods:QUASAR™‐Body‐Phantom was used in this study with oval curved‐surfaces to mimic breast, chest wall and head‐and‐neck sites.A CT‐scan was obtained with five radio‐opaque markers(ROM) placed on the surface of phantom to mimic the range of incident angles for measurements and dose prediction using 2mm slice thickness.At each ROM, small structure(1mmx2mm) were contoured to obtain mean‐doses from TPS.Calculations were performed for open‐field,dynamic‐wedge,physical‐wedge,IMRT and VMAT using Varian‐21EX,6&15MV photons using twogrid‐sizes:2.5mm and 1mm.Calibration checks were performed to ensure that MOSFETs response were within ±5%.Surface‐doses were measured at five locations and compared with TPS calculations.Results:For 6MV: 2.5mm grid‐size,mean calculated doses(MCD)were higher by 10%(±7.6),10%(±7.6),20%(±8.5),40%(±7.5),30%(±6.9) and for 1mm grid‐size MCD were higher by 0%(±5.7),0%(±4.2),0%(±5.5),1.2%(±5.0),1.1% (±7.8) for open‐field,dynamic‐wedge,physical‐wedge,IMRT,VMAT respectively.For 15MV: 2.5mm grid‐size,MCD were higher by 30%(±14.6),30%(±14.6),30%(±14.0),40%(±11.0),30%(±3.5)and for 1mm grid‐size MCD were higher by 10% (±10.6), 10%(±9.8),10%(±8.0),30%(±7.8),10%(±3.8) for open‐field, dynamic‐wedge, physical‐wedge, IMRT, VMAT respectively.For 6MV, 86% and 56% of all measured values agreed better than ±20% for 1mm and 2.5mm grid‐sizes respectively. For 18MV, 56% and 18% of all measured‐values agreed better than ±20% for 1mm and 2.5mm grid‐sizes respectively.Conclusion:Reliable Skin‐dose calculations by TPS can be very difficult due to steep dose‐gradient and inaccurate beam‐modelling in buildup region.Our results showed that Eclipse over‐estimates surface‐dose.Impact of grid‐size is also significant,surface‐dose increased up to 40% from 1mm to 2.5mm,however, 1mm calculated‐values closely agrees with measurements. Due to large uncertnities in skin‐dose predictions from TPS,outmost caution must be exercised when skin dose is evaluated,a sufficiently smaller grid‐size(1mm)can improve the accuracy and MOSFETs can be used for verification.

For stereotactic ablative body radiotherapy (SABR) in lung cancer patients, Radiation Therapy Oncology Group (RTOG) protocols currently require radiation dose to be calculated using tissue heterogeneity corrections. Dosimetric criteria of RTOG 0813 were established based on the results obtained from non‐Monte Carlo (MC) algorithms, such as superposition/convolutions. Clinically, MC‐based algorithms are now routinely used for lung SABR dose calculations. It is essential to confirm that MC calculations in lung SABR meet RTOG guidelines. This report evaluates iPlan MC plans for SABR in lung cancer patients using dose‐volume histogram normalization per current RTOG 0813 compliance criteria. Eighteen Stage I‐II non‐small cell lung cancer (NSCLC) patients with centrally located tumors, who underwent MC‐based lung SABR with heterogeneity correction using X‐ray Voxel Monte Carlo (XVMC) algorithm (BrainLAB iPlan version 4.1.2), were analyzed. Total dose of 60 Gy in 5 fractions was delivered to planning target volume (PTV) with at least . Internal target volumes (ITVs) were delineated on maximum intensity projection (MIP) images of 4D CT scans. PTV ( margin) volumes ranged from 10.0 to 99.9 cc (). Organs at risk (OARs) were delineated on average images of 4D CT scans. Optimal clinical MC SABR plans were generated using a combination of non‐coplanar conformal arcs and beams for the Novalis‐TX consisting of high definition multileaf collimators (MLCs) and 6 MV‐SRS (1000MU/min) mode. All plans were evaluated using the RTOG 0813 high and intermediate dose spillage criteria: conformity index (R100%), ratio of 50% isodose volume to the PTV (R50%), maximum dose 2 cm away from PTV in any direction (), and percent of normal lung receiving or more. Other organs‐at‐risk (OARs) doses were tabulated, including the volume of normal lung receiving , maximum cord dose, dose to of heart, and dose to of esophagus. Only six out of 18 patients met all RTOG 0813 compliance criteria. Eight of 18 patients had minor deviations in R100%, four in R50%, and nine in . However, only one patient had minor deviation in . All other OARs doses, such as maximum cord dose, dose to of heart, and dose to of esophagus, were satisfactory for RTOG criteria, except for one patient, for whom the dose to of heart was higher than RTOG guidelines. The preliminary results for our limited iPlan XVMC dose calculations indicate that the majority (i.e., 2/3) of our patients had minor deviations in the dosimetric guidelines set by RTOG 0813 protocol in one way or another. When using an exclusive highly sophisticated XVMC algorithm, the RTOG 0813 dosimetric compliance criteria such as R100% and may need to be revisited. Based on our limited number of patient datasets, in general, about 6% for R100% and 9% for corrections could be applied to pass the RTOG 0813 compliance criteria in most of those patients. More patient plans need to be evaluated to make recommendation for R50%. No adjustment is necessary for OAR dose tolerances, including normal lung . In order to establish new MC specific dose parameters, further investigation with a large cohort of patients including central, as well as peripheral lung tumors, is anticipated and strongly recommended.PACS number: 8087

Purpose:To compare dose distributions calculated using the iPlan XVMC algorithm and heterogeneities corrected/uncorrected Pencil Beam (PB‐hete/PB‐homo) algorithms for SBRT treatments of lung tumors.Methods:Ten patients with centrally located solitary lung tumors were treated using MC‐based SBRT to 60Gy in 5 fractions for PTVV100%=95%. ITV was delineated on MIP‐images based on 4D‐CT scans. PTVs(ITV+5mm margins) ranged from 10.1–106.5cc(mean=48.6cc). MC‐SBRT plans were generated with a combination of non‐coplanar conformal arcs/beams using iPlan‐XVMC‐algorithm (BrainLABiPlan ver.4.1.2) for Novalis‐TX consisting of HD‐MLCs and 6MV‐SRS(1000MU/min) mode, following RTOG 0813 dosimetric criteria. For comparison, PB‐hete/PB‐homo algorithms were used to re‐calculate dose distributions using same beam configurations, MLCs/monitor units. Plans were evaluated with isocenter/maximal/mean doses to PTV. Normal lung doses were evaluated with V5/V10/V20 and mean‐lung‐dose(MLD), excluding PTV. Other OAR doses such as maximal spinal cord/2cc‐esophagus/max bronchial tree (BT/maximal heart doses were tabulated.Results:Maximal/mean/isocenter doses to PTV calculated by PB‐hete were uniformly larger than MC plans by a factors of 1.09/1.13/1.07, on average, whereas they were consistently lower by PB‐homo by a factors of 0.9/0.84/0.9, respectively. The volume covered by 5Gy/10Gy/20Gy isodose‐lines of the lung were comparable (average within±3%) when calculated by PB‐hete compared to XVMC, but, consistently lower by PB‐homo by a factors of 0.90/0.88/0.85, respectively. MLD was higher with PB‐hete by 1.05, but, lower by PB‐homo by 0.9, on average, compared to XVMC. XVMC max‐cord/max‐BT/max‐heart and 2cc of esophagus doses were comparable to PB‐hete; however, PB‐homo underestimates by a factors of 0.82/0.89/0.88/0.86, on average, respectively.Conclusion:PB‐hete significantly overestimates dose to PTV relative to XVMC ‐hence underdosing the target. MC is more complex and accurate with tissue‐heterogeneities. The magnitude of variation significantly varies with ‘small‐island‐tumor’ surrounded by low‐density lung tissues ‐PB algorithms lacks later electron scattering. Dose calculation with XVMC for lung SBRT is routinely performed in our clinic, its performance for head' neck/sinus cases will also be investigated.

We present the recently updated preliminary results of an on-going phase I / II trial with the purpose of determining the safety, feasibility and efficacy of post-prostatectomy radiation therapy (RT), hormonal therapy and concurrent docetaxel in patients with high risk pathologic (p) T2-3N0M0 prostate cancer. Post-prostatectomy high risk prostate cancer was defined as clinically non-metastatic disease with either an undetectable, persistent or rising PSA with 1 or more of the following clinical-pathologic features: (1) pT2-T3aN0 disease, positive or negative margins, with either (a) a gleason score (GS) of ≥8, and/or (b) a PSA doubling time of ≤10 months, and/or (c) with a pre-RT PSA of ≥1.0 ng/ml; and/or (2) pT3bN0 disease. The tri-modality treatment consisted of 6 months of hormonal therapy [Casodex (50 mg po daily), and Zoladex (10.8 mg sc q 3 mos x 2) or Lupron (22.5 mg im q 3 mos x 2)], RT to 66.0 Gy at 2.0 Gy/fraction (fx) once daily (50 Gy to the surgical bed followed by a 16 Gy Boost at 2.0 Gy/fx using either 3-D conformal radiation therapy or IMRT, usually begun after 2 months of hormonal therapy), and concurrent weekly docetaxel at 20 mg/m2 x 7 infusions. Between October 2008 and February 2014, a total of 26 patients have been enrolled to this on-going phase I/II clinical trial. The clinical and disease characteristics of these 26 patients are as follows: Median age, years (range) = 63 (56 - 74); GS was as follows: 3+3 = 6 in 1 patient, 3+4 = 7 in 6 patients, 4+3 = 7 in 5, 3+5 = 8 in 3, 4+4 = 8 in 3, 4+5 = 9 in 5 and 5+4 = 9 in 3; resection margin was negative in 10 patients, close in 2 and positive in 14; extracapsular extension was absent in 8 patients, and present in 18; seminal vesicle invasion was present in 12 patients and absent in 14; and pathologic T-stage was as follows: pT2a = 2 patients, pT2c = 5, pT3a = 8 and pT3b = 11. Nine patients are in the adjuvant RT category while the remaining 17 are in the salvage RT category. Eighteen of the 26 enrolled patients have completed their entire tri-modality therapy. All of these 18 patients completed their full dose of RT (66 Gy). These 18 patients also received a median of 7 weekly docetaxel infusions (range = 5 - 8). Only 2 of these 18 patients experienced grade ≥3 GI possibly treatment-related acute toxicity, both of whom were on stool softners and / or laxatives preceding their grade 3 diarrhea. Among the 8 of 26 remaining patients, 2 of the 8 have completed their entire chemoradiation therapy treatments without any acute grade ≥3 GI / GU toxicity while the other 6 recently started their protocol therapy. The recently updated preliminary results of our on-going phase I/II clinical trial with an accrual goal of ≥40 patients indicate that our post-prostatectomy tri-modality therapy is well tolerated with a very high feasibility rate in patients with high risk pT2-3N0M0 prostate cancer.

Purpose: Four‐dimensional‐computed‐tomography(4D‐CT) imaging for target‐volume delineation and cone‐beam‐tomography(CBCT) for treatment localization are widely utilized in lung‐SABR.Aim of this study was to perform a quantitative‐assessment and inter‐comparison of Internal‐targetvolumes(ITV) drawn on various phases of breathing‐cycle 4D‐CT‐scans, Maximum‐intensity‐projection(MIP), average‐intensity‐projection(AIP)and static CT‐scans of lung‐motion‐phantom to simulate lung‐SABR patient geometry. We also analyzed and compared the ITVs drawn on freebreathing‐ CBCT. Materials & Methods: 4D‐CT‐scans were acquired on Philips big‐bore 16slice CT and Bellows‐respiratory monitoring‐system using retrospective phase‐binning method. Each respiratory cycle divided into 10‐phases. Quasar‐Phantom with lung‐inserts and 3cm‐diameter nylonball to simulate tumor and was placed on respiratory‐motion‐platform for 4D‐CT and CBCT‐acquisition. Amplitudes of motions: 0.5,1.0,2.0,3.0cm in superior‐inferior direction with breathing‐cycle time of 6,5,4,6sec, respectively used.4D‐CTs with 10‐phases(0%to90%)for each excursion‐set and 3D‐CT for static‐phantom exported to iPlan treatment‐planningsystem(TPS). Tumor‐volumes delineated in all phases of 4D‐CT, MIP,AIP,CBCT scans using fixed‐HU‐threshold(−500to1000)values automatically.For each 4D‐dataset ITV obtained by unifying the tumorcontours on all phases.CBCT‐ITV‐volumes were drawn in Eclipse‐TPS. Results: Mean volume of tumor contours for all phases compared with static 3D‐CT were 0.62±0.08%, 1.67±0.26%, 4.77±0.54% and 9.27±1.23% for 0.5cm,1cm,2cm,3cm excursions respectively. Differences of mean Union‐ITV with MIP‐ITV were close(≤2.4%).Mean Union‐ITV from expected‐theoretical values differed from −4.9% to 3.8%.Union‐ITV and MIP‐ITV were closer within 2.3%. AIP‐ITVs were underestimated from 14 to 32% compared to union‐ITV for all motion datasets. Differences of −5.9% to −44% and −5% to 6.7% for CBCT‐ITV from MIP‐ITV and AIP‐ITV respectively.Motion excursions and centroid positions were within 2mm for 4D‐CT and CBCT‐ITVs to that of expected values. Conclusion: 4D‐CT MIP‐ITV and Union‐ITV showed very good agreement that validates that ITV can be fast contoured on MIP.Contouring ITV in AIP must be avoided as it significantly underestimates the volume with all excursions. Free breathing CBCT‐ITV showed good agreement with AIP‐ITV but underestimated the MIP‐ITV. Estimation of excursions and centroid values for 4D‐CT and CBCT were in good agreement with expected values.

Purpose:Brachytherapy plays a crucial role in management of cervix cancer. MRI compatible applicators have made it possible to accurately delineate gross‐target‐volume(GTV) and organs‐at‐risk(OAR) volumes, as well as directly plan, optimize and adapt dose‐distribution for each insertion. We sought to compare DVH of tumor‐coverage and OARs to traditional Point‐A, ICRU‐38 bladder and rectum point‐doses for four different planning‐techniques.Methods:MRI based 3D‐planning was performed on Nucletron‐Oncentra‐TPS for 3 selected patients with varying tumor‐sizes and anatomy.GTV,high‐risk‐clinical‐target‐volume(HR‐CTV),intermediate‐risk‐clinical‐target‐volume(IR‐CTV) and OARs: rectum, bladder, sigmoid‐colon, vaginal‐mucosa were delineated. Three conventionally used techniques: mg‐Radium‐equivalent(RaEq),equal‐dwell‐weights(EDW),Medical‐College‐of‐Wisconsin proposed points‐optimization(MCWO) and a manual‐graphical‐optimization(MGO) volume‐coverage based technique were applied for each patient. Prescription was 6Gy delivered to point‐A in Conventional techniques (RaEq, EDW, MCWO). For MGO, goal was to achieve 90%‐coverage (D90) to HR‐CTV with prescription‐dose. ICRU point doses for rectum and bladder, point‐A doses, DVH‐doses for HR‐CTV‐D90,0.1cc‐volume(D0.1),1ccvolume(D1),2cc‐volume(D2) were collected for all plans and analyzed. Results:Mean D90 for HR‐CTV normalized to MGO were 0.89,0.84,0.9,1.0 for EDW, RaEq, MCWO, MGO respectively. Mean point‐A doses were 21.7% higher for MGO. Conventional techniques with Point‐A prescriptions under covered HR‐CTV‐D90 by average of 12% as compared to MGO. Rectum, bladder and sigmoid doses were highest in MGO‐plans for ICRU points as well as D0.1,D1 and D2 doses. Among conventional‐techniques, rectum and bladder ICRU and DVH doses(0.1,1,2cc) were not significantly different (within 7%).Rectum D0.1 provided good estimation of ICRU‐rectum‐point doses (within 3.9%),rectum D0.1 were higher from 0.8 to 3.9% while bladder D0.1 overestimated the bladder ICRU point dose up to 43% for conventional‐techniques.Bladder‐D2 provided a good estimation of ICRU bladder point‐doses(within 3.6%) for conventional‐techniques. This correlation is not observed for MGO plans perhaps due to steering of isodose line, leading to unpredictable dwell‐weighting.Conclusion:MRI based HDR‐planning provides accurate delineation of tumor volumes and normal structures, and optimized tumor‐coverage can be achieved with acceptable normal‐tissue doses. This study showed that for conventional techniques D0.1 rectum dose and D2 bladder dose are good representation of ICRU‐reference‐point doses.