N Pahlajani

Radiotherapy Doses of 80 Gy and Higher Are Associated With Lower Mortality in Men With Gleason Score 8 to 10 Prostate Cancer

PURPOSEnMen with Gleason score (GS) 8-10 prostate cancer (PCa) are assumed to have a high risk of micrometastatic disease at presentation. However, local failure is also a major problem. We sought to establish the importance of more aggressive local radiotherapy (RT) to ≥80 Gy.nnnMETHODS AND MATERIALSnThere were 226 men treated consecutively with RT ± ADT from 1988 to 2002 for GS 8-10 PCa. Conventional, three-dimensional conformal or intensity-modulated (IM) RT was used. Radiation dose was divided into three groups: (1) <75 Gy (n = 50); (2) 75-79.9 Gy (n = 60); or (3) ≥80 Gy (n = 116). The endpoints examined included biochemical failure (BF; nadir + 2 definition), distant metastasis (DM), cause-specific mortality, and overall mortality (OM).nnnRESULTSnMedian follow-up was 66, 71, and 58 months for Groups 1, 2, and 3. On Fine and Grays competing risk regression analysis, significant predictors of reduced BF were RT dose ≥80 Gy (p = 0.011) and androgen deprivation therapy duration ≥24 months (p = 0.033). In a similar model of DM, only RT dose ≥80 Gy was significant (p = 0.007). On Cox regression analysis, significant predictors of reduced OM were RT dose ≥80 Gy (p = 0.035) and T category (T3/4 vs. T1, p = 0.041). Dose was not a significant determinant of cause-specific mortality. Results for RT dose were similar in a model with RT dose and ADT duration as continuous variables.nnnCONCLUSIONnThe results indicate that RT dose escalation to ≥80 Gy is associated with lower risks of BF, DM, and OM in men with GS 8-10 PCa, independently of androgen deprivation therapy.

Quantifying Rigid and Nonrigid Motion of Liver Tumors During Stereotactic Body Radiation Therapy

PURPOSEnTo quantify rigid and nonrigid motion of liver tumors using reconstructed 3-dimensional (3D) fiducials from stereo imaging during CyberKnife-based stereotactic body radiation therapy (SBRT).nnnMETHODS AND MATERIALSnTwenty-three liver patients treated with 3 fractions of SBRT were used in this study. After 2 orthogonal kilovoltage images were taken during treatment, the 3D locations of the fiducials were generated by the CyberKnife system and validated using geometric derivations. A total of 4824 pairs of kilovoltage images from start to end of treatment were analyzed. For rigid motion, the rotational angles and translational shifts were reported by aligning 3D fiducial groups from different image pairs, using least-squares fitting. For nonrigid motion, we quantified interfractional tumor volume variations by using the proportional volume derived from the fiducials, which correlates to the sum of interfiducial distances. The individual fiducial displacements were also reported (1) after rigid corrections and (2) without angle corrections.nnnRESULTSnThe proportional volume derived by the fiducials demonstrated a volume-increasing trend in the second (101.9% ± 3.6%) and third (101.0 ± 5.9%) fractions among most patients, possibly due to radiation-induced edema. For all patients, the translational shifts in left-right, anteroposterior, and superoinferior directions were 2.1 ± 2.3 mm, 2.9 ± 2.8 mm, and 6.4 ± 5.5 mm, respectively. The greatest translational shifts occurred in the superoinferior direction, likely due to respiratory motion from the diaphragm. The rotational angles in roll, pitch, and yaw were 1.2° ± 1.8°, 1.8° ± 2.4°, and 1.7° ± 2.1°, respectively. The 3D individual fiducial displacements with rigid corrections were 0.2 ± 0.2 mm and increased to 0.5 ± 0.4 mm without rotational corrections.nnnCONCLUSIONSnAccurate 3D locations of internal fiducials can be reconstructed from stereo imaging during treatment. As an effective surrogate to tumor motion, fiducials provide a close estimation of both rigid and nonrigid motion of liver tumors. The reported displacements could be further utilized for tumor margin definition and motion management in conventional linear accelerator-based liver SBRT.

Stereotactic body radiotherapy as an alternative to brachytherapy in gynecologic cancer.

Introduction. Brachytherapy plays a key role in the treatment of many gynecologic cancers. However, some patients are unable to tolerate brachytherapy for medical or other reasons. For these patients, stereotactic body radiotherapy (SBRT) offers an alternative form of treatment. Methods. Retrospective review of patients prospectively collected on SBRT database is conducted. A total of 11 gynecologic patients who could not have brachytherapy received SBRT for treatment of their malignancies. Five patients have been candidates for interstitial brachytherapy, and six have required tandem and ovoid brachytherapy. Median SBRT dose was 25u2009Gy in five fractions. Results. At last followup, eight patients were alive, and three patients had died of progressive disease. One patient had a local recurrence. Median followup for surviving patients was 420 days (median followup for all patients was 120 days). Two patients had acute toxicity (G2 dysuria and G2 GI), and one patient had late toxicity (G3 GI, rectal bleeding requiring cauterization). Conclusions. Our data show acceptable toxicity and outcome for gynecologic patients treated with SBRT who were unable to receive a brachytherapy boost. This treatment modality should be further evaluated in a phase II study.

Dosimetric investigation of accelerated partial breast irradiation (APBI) using CyberKnife

PURPOSEnTo investigate the dosimetric feasibility of accelerated partial breast irradiation (APBI) using CyberKnife.nnnMETHODSnFourteen previously treated patients with early-stage breast cancer were selected for a retrospective study. Six of these patients had been treated to 38.5 Gy in 10 fractions in a phase III accelerated partial breast trial and the rest of the patients were treated to 50.4 Gy in 28 fractions. In this planning study, the guidelines in the protocol for the phase III partial breast trial were followed for organ delineation and CyberKnife planning. The achievable dosimetric parameters from all CyberKnife plans were compared to Intensity-modulated radiation therapy (IMRT) and 3D-CRT methods. The reproducibility of the dose delivery with and without respiratory motion was assessed through delivering a patient plan to a breast phantom. Different dose calculation algorithms were also compared between ray tracing and Monte Carlo.nnnRESULTSnFor all the patients in the study, the dosimetric parameters met the guidelines from the NSABP B39∕RTOG 0413 protocol strictly. The mean PTV volume covered by 100% of the prescription dose was 95.7 ± 0.7% (94.7%-97.1%). The mean maximal dose was 104 ± 2% of the prescription dose. The mean V(50%) and mean V(100%) to the ipsilateral normal breast were 23.1 ± 11.6% and 9.0 ± 5.8%, respectively. The conformity index of all plans was 1.14 ± 0.04. The maximum dose to the contralateral breast varied from 1.3 cGy to 111 cGy. The mean V(5%) and mean V(30%) to the contralateral and ipsilateral lungs were 1.0 ± 1.6% and 1.3 ± 1.2%, respectively. In our study, the mean V(5%) to the heart was 0.2 ± 0.5% for right-sided tumors and 9.4 ± 10.1% for left-sided tumors. Compared with IMRT and 3D-CRT planning, the PTV coverage from CyberKnife planning was the highest, and the ratio of V(20%) to V(100%) of the breast from CyberKnife planning was the smallest. The heart and lung doses were similar in all the techniques except that the V(5%) for the lung and heart in CyberKnife planning was slightly higher.nnnCONCLUSIONSnThe dosimetric feasibility of APBI using CyberKnife was investigated in this retrospective study. All the dosimetric parameters strictly met the guidelines from the NSABP B39∕RTOG 0413 protocol. With advanced real-time tracking capability, CyberKnife should provide better target coverage and spare nearby critical organs for APBI treatment.

Low toxicity for lung tumors near the mediastinum treated with stereotactic body radiation therapy.

PURPOSEnTo report the local control, survival, and low toxicity observed at the Cooper University Hospital CyberKnife Center post stereotactic body radiation therapy (SBRT) in the treatment of lung tumors near the mediastinum.nnnMETHODS AND MATERIALSnTwenty-four medically inoperable lung cancer patients with tumors near the mediastinum were treated using the Accuray CyberKnife system (Accuray, Sunnyvale, CA) with Monte Carlo dose calculations and heterogeneity corrections from July 2008 to May 2010. The prescription dose ranged from 28.5 Gy to 60 Gy in 3-5 fractions. For conventional fractionation schemes, Emami et al(1) organized the dose tolerance limits into a unified format for clinical utility and partitioned them into 2 risk levels (5% and 50%) with preset volumes for most critical structures throughout the body. In contrast, statistical SBRT dose tolerance limits for mediastinal structures have not been established yet. We have sufficient experience at least to begin organizing a unified format with low-risk and high-risk partitions and preset volumes for 1-5 fractions exposing mediastinal structures. With the help of the (dose-volume histogram) DVH Evaluator, a software tool developed by our senior author, each treatment plan was assessed for safety and feasibility prior to treatment. The DVH Evaluator was also used to analyze the follow-up data and to create graphs of risk, called DVH Risk Maps, superimposing clinical data onto the unified SBRT dose tolerance limits.nnnRESULTSnIt was not feasible to prescribe the doses of peripheral lung lesions for all tumors near the mediastinum because of known toxicity. The crude local tumor control rate achieved in our series was 92%. Median survival was 26.8 months for the primary lung cases and 9.6 months for the metastatic cases. No patients experienced grade 3 or higher toxicities.nnnCONCLUSIONSnWe affirm that SBRT is feasible in the treatment of centrally located lung cancers when the dose tolerance limits of critical structures are diligently respected. The low adverse event rates that we have experienced, combined with a good local tumor control rate, are encouraging.

The impact of dose-escalated radiotherapy plus androgen deprivation for prostate cancer using 2 linked nomograms.

Randomized trials have demonstrated that escalated‐dose external‐beam radiotherapy (EDRT) is better than standard‐dose radiotherapy (SDRT) for patients with prostate cancer and that adding androgen‐deprivation therapy (ADT) to SDRT is better than SDRT alone; however, no trials have compared EDRT versus SDRT plus ADT or EDRT versus EDRT plus ADT. The authors designed a model to estimate the results of various doses of radiotherapy (RT) combined with various durations of ADT.

Factors that may determine the targeting accuracy of image-guided radiosurgery

PURPOSEnThe AAPM TG-135 report is a landmark recommendation for the quality assurance (QA) of image-guided robotic radiosurgery. The purpose of this paper is to present results pertaining to intentionally offsetting the phantom as recommended by TG-135 and to present data on targeting algorithm accuracy as a function of imager parameters in less than ideal circumstances, which had not been available at the time of publication of TG-135.nnnMETHODSnAll tests in this study were performed at the Cooper University Hospital CyberKnife Center in Mt. Laurel, NJ. For intentional offsets, initial tests were performed on the Accuray-supplied anthropomorphic head and neck phantom, whereas for subsequent tests, the Accuray-supplied alignment quality assurance (AQA) phantom was used. To simulate the effects of imager parameters for larger patients, slabs of Blue Water (Standard Imaging, Inc., Middleton, WI) were added to attenuate the x-ray images in some of the tests. In conjunction with attenuated x-ray tests, the number of fiducials was varied by systematically deselecting them one at a time at the CyberKnife console.nnnRESULTSnTests using the AQA phantom verified that submillimeter alignments were consistently achieved even with intentional shifts and rotations of up to 10.0 mm and 1.0°, respectively. An analysis of 17 months of daily QA alignment tests showed that submillimeter alignments were achieved more than 99% of the time even with such intentional shifts and rotations of the phantom. When additional slabs of Blue Water were added to simulate patient attenuation of the x-ray images, targeting errors could be induced depending on imager parameters and the amount of Blue Water used. A series of consecutive tests showed that two helpful variables to ensure good accuracy of the system were (1) the fiducial extraction confidence level (FECL) system parameter and (2) the number of targeted fiducials. When fewer than four fiducials were used, the FECL reported by the CyberKnife was sometimes high even when a false lock occurred, so using multiple fiducials helped to ensure reliable targeting.nnnCONCLUSIONSnRadiosurgery requires the highest degree of targeting accuracy, and in our experience, the CyberKnife has been able to maintain submillimeter accuracy consistently. It has been verified that our CyberKnife can correct for phantom shifts of up to 10.0 mm and rotations of up to 1.0°. It has also been discovered that false locks are more likely to occur with a single fiducial than with multiple fiducials. Although targeting accuracy can only be measured on a phantom, the insight gained from analyzing the QA tests can help us in devising better strategies for achieving the best treatment for our patients.

SU‐E‐J‐225: Quantitative Evaluation of Rigid and Non‐Rigid Motion of Liver Tumors Using Stereo Imaging During SBRT

PURPOSEnTo quantitatively evaluate rigid and nonrigid motion of liver tumors based on fiducial tracking in 3D by stereo imaging during CyberKnife SBRT.nnnMETHODSnTwenty-five liver patients previously treated with three-fractions of SBRT were retrospectively recruited in this study. During treatment, the 3D locations of fiducials were reported by the CyberKnife system after two orthogonal kV X-ray images were taken and further validated by geometry derivations. A total of 5004 pairs of X-ray images acquired during the course of treatment for all the patients, were analyzed. For rigid motion, the rotational angles and translational shifts by aligning 3D fiducial groups in different image pairs after least-square fitting were reported. For nonrigid motion, the relative interfractional tumor shape variations were reported and correlated to the sum of inter-fiducial distances. The individual fiducial displacements were also reported after rigid corrections and without angle corrections.nnnRESULTSnThe relative tumor volume variation indicated by the inter-fiducial distances demonstrated an increasing trend in the second (101.6±3.4%) and third fraction (101.2±5.6%) among most patients. The cause could be possibly due to radiation-induced edema. For all the patients, the translational shift was 8.1±5.7 mm, with shifts in LR, AP and SI were 2.1±2.4 mm, 2.8±2.9 mm and 6.7±5.1 mm, respectively. The greatest translation shift occurred in SI, mainly due the breathing motion of diaphragm The rotational angles were 1.1±1.7°, 1.9±2.6° and 1.6±2.2°, in roll, pitch, and yaw, respectively. The 3D fiducial displacement with rigid corrections were 0.2±0.2 mm and increased to 0.6±0.3 mm without rotational corrections.nnnCONCLUSIONnThe fiducial locations in 3D can be precisely reconstructed from CyberKnife stereo imaging system during treatment. The fiducials provide close estimation of both rigid and nonrigid motion of .liver tumors. The reported data could be further utilized for tumor margin design and motion management in in conventional linac-based treatments.

SU‐E‐T‐883: Clinical Application of Monte Carlo for SBRT: Mediastinal Lung

Purpose: Treatment planning systems have provided Monte Carlo dose calculations for several years but many physicians are still hesitant to use them clinically due to lack of data. Therefore we recalculated 200 Ray Tracing treatment plans using Monte Carlo with heterogeneity corrections and compared to SBRT dose tolerance limits. Methods: From among these 200 CyberKnife cases, 25 mediastinal lung cases are presented in this study. An extensive literature review obtained 105 published SBRT dose tolerance limits for the mediastinal critical structures aorta, bronchi, esophagus, heart, and trachea. These limits were partitioned into high‐risk and low‐risk categories. The DVH Evaluator software tool was used to generate DVH Risk Maps for these critical structures, which superimpose a) published dose tolerance limits b) unified high‐risk and low‐risk trends and c) published adverse event doses, onto Monte Carlo patient data to assess risk of adverse events. Results: Recalculated treatment plan data is within the expected range of published SBRT dose tolerance limits, providing optimism for clinical use. None of the patients experienced any Grade 3 or higher adverse events. The low‐risk dose tolerance limits were exceeded 22 times in these cases with no severe adverse event, thus helping to validate their safety. Conclusions: The range of doses calculated by Monte Carlo for our historical patient data is compatible with published SBRT dose tolerance limits. SBRT dose tolerance limits should be fine‐tuned by Monte Carlo dose calculations in long‐term statistical followup studies. Disclosure: The first author has developed the DVH Evaluator software.

MO‐D‐BRB‐07: Phantom Validation and Clinical Application of Monte Carlo for Small Field SBRT

Purpose: Small field dosimetry is challenging in homogeneous medium and extremely difficult in an inhomogeneous medium. Monte Carlo dose calculation algorithms are considered as the most accurate for treatment planning. We present our validation of the Monte Carlo algorithm in the Accuray Multiplan system using measurements in a cork phantom. We also recalculated Ray Tracing treatment plans with the Monte Carlo algorithm and compared to SBRT dose tolerance limits. Methods: In our validation measurements with a cork phantom, an Exradin A16 ion chamber was used for collimators from 60mm to 20mm on a CyberKnife, and a PTW 60012 stereotactic diode for collimators from 60mm to 5mm. A literature review of more than 500 published SBRT dose tolerance limits was partitioned into high‐risk and low‐risk categories. Two hundred CyberKnife treatment plans were recalculated using Monte Carlo and compared to the dose limits. The DVH Evaluator software tool was used to generate DVH Risk Maps for 25 critical structures throughout the body, which superimpose a) published dose tolerance limits b) unified high‐risk and low‐risk trends and c) published adverse event doses, onto Monte Carlo patient doses to assess risk of adverse events. Results: The Monte Carlo calculations matched the Exradin A16 measurements to within 2.5% for field sizes down to 20mm, and matched the PTW 60012 measurements to within 2.5% for all field sizes down to 5mm. Recalculated treatment plan data is within the expected range of published SBRT dose tolerance limits, providing optimism for clinical use. Conclusions: The Accuray MultiPlan Monte Carlo algorithm is accurate even for small fields in heterogeneous media. The range of doses calculated by Monte Carlo for our patient data is compatible with published SBRT dose tolerance limits. SBRT dose tolerance limits should be fine‐tuned by Monte Carlo dose calculations in long‐term statistical followup studies. Disclosure: The first author has developed the DVH Evaluator software.