R Lalonde

Concurrent Chemotherapy and Intensity-modulated Radiation Therapy for Anal Carcinoma — Clinical Outcomes in a Large National Cancer Institute-designated Integrated Cancer Centre Network

AIMSnTo report the clinical outcomes of patients with anal carcinoma treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy in a large integrated academic-community cancer centre network.nnnMATERIALS AND METHODSnSeventy-eight patients were treated with IMRT for anal carcinoma at 13 community cancer centres. IMRT planning for all centres was carried out at one central location. Sixty-five patients (83%) were T1-T2, 64% were N0, 9% were M1; five patients were HIV positive. All but one patient received concurrent chemotherapy. The median dose to the pelvis including inguinal nodes was 45 Gy. The primary site and involved nodes were boosted to a median dose of 55.8 Gy. All acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 3.0.nnnRESULTSnThe median follow-up for the entire cohort was 16 months (range 0-72 months). Acute grade ≥3 toxicity included 27.7% gastrointestinal and 29.0% dermatological. Acute grade 4 haematological toxicity occurred in 12.9% of patients. Sixty-four (88.9%) patients experienced a complete response. The 2 year colostomy-free survival, overall survival, freedom from local failure and freedom from distant failure rates were 81.2, 86.9, 83.6 and 81.8%, respectively.nnnCONCLUSIONSnEarly results seem to confirm that IMRT used concurrently with chemotherapy for treatment of anal carcinoma is effective and well tolerated. This complex treatment can be safely and effectively carried out in a large integrated healthcare network.

Four-dimensional computed tomography-based respiratory-gated whole-abdominal intensity-modulated radiation therapy for ovarian cancer: a feasibility study.

This study assesses the feasibility and implementation of respiratory-gated whole-abdominal intensity-modulated radiation therapy (RG-WAIMRT). Three patients were treated with RG-WAIMRT. The planning target volume (PTV1) included the entire peritoneal cavity and a pelvic boost field was created (PTV2). The dose prescribed was 30 Gy to PTV1 and 14.4 Gy to PTV2. For comparison, a conventional three-dimensional (3D) plan was generated for each patient. In the WAIMRT plan, an average of 90% of PTV1 received 30 Gy compared to 70% for the conventional 3D plan. The percent volume receiving 30 Gy (V30) for liver averaged 54% (WAIMRT) vs 43% (3D). The percent volume receiving 20 Gy (V20) for kidneys averaged 19% vs 0%, and the mean V20 for bone marrow was 74% vs 83%, respectively. Major acute toxicities were anemia (grade 2: 1/3), leukopenia (grade 3: 2/3 patients), and thrombocytopenia (grade 2: 1/3 patients, grade 3: 1/3 patients). One patient could not complete the whole-abdomen field after 19.5 Gy because of persistent nausea. No major subacute toxicity has been reported. WAIMRT demonstrated superior target coverage and reduced dose to bone marrow, with a slightly increased dose to liver and kidneys. WAIMRT is a novel and feasible technique for ovarian cancer treatment.

Clinical implementation and evaluation of the Acuros dose calculation algorithm

Abstract Purpose The main aim of this study is to validate the Acuros XB dose calculation algorithm for a Varian Clinac iX linac in our clinics, and subsequently compare it with the wildely used AAA algorithm. Methods and materials The source models for both Acuros XB and AAA were configured by importing the same measured beam data into Eclipse treatment planning system. Both algorithms were validated by comparing calculated dose with measured dose on a homogeneous water phantom for field sizes ranging from 6 cm × 6 cm to 40 cm × 40 cm. Central axis and off‐axis points with different depths were chosen for the comparison. In addition, the accuracy of Acuros was evaluated for wedge fields with wedge angles from 15 to 60°. Similarly, variable field sizes for an inhomogeneous phantom were chosen to validate the Acuros algorithm. In addition, doses calculated by Acuros and AAA at the center of lung equivalent tissue from three different VMAT plans were compared to the ion chamber measured doses in QUASAR phantom, and the calculated dose distributions by the two algorithms and their differences on patients were compared. Computation time on VMAT plans was also evaluated for Acuros and AAA. Differences between dose‐to‐water (calculated by AAA and Acuros XB) and dose‐to‐medium (calculated by Acuros XB) on patient plans were compared and evaluated. Results For open 6 MV photon beams on the homogeneous water phantom, both Acuros XB and AAA calculations were within 1% of measurements. For 23 MV photon beams, the calculated doses were within 1.5% of measured doses for Acuros XB and 2% for AAA. Testing on the inhomogeneous phantom demonstrated that AAA overestimated doses by up to 8.96% at a point close to lung/solid water interface, while Acuros XB reduced that to 1.64%. The test on QUASAR phantom showed that Acuros achieved better agreement in lung equivalent tissue while AAA underestimated dose for all VMAT plans by up to 2.7%. Acuros XB computation time was about three times faster than AAA for VMAT plans, and computation time for other plans will be discussed at the end. Maximum difference between dose calculated by AAA and dose‐to‐medium by Acuros XB (Acuros_Dm,m) was 4.3% on patient plans at the isocenter, and maximum difference between D100 calculated by AAA and by Acuros_Dm,m was 11.3%. When calculating the maximum dose to spinal cord on patient plans, differences between dose calculated by AAA and Acuros_Dm,m were more than 3%. Conclusion Compared with AAA, Acuros XB improves accuracy in the presence of inhomogeneity, and also significantly reduces computation time for VMAT plans. Dose differences between AAA and Acuros_Dw,m were generally less than the dose differences between AAA and Acuros_Dm,m. Clinical practitioners should consider making Acuros XB available in clinics, however, further investigation and clarification is needed about which dose reporting mode (dose‐to‐water or dose‐to‐medium) should be used in clinics.

A dosimetric evaluation of the IAEA‐AAPM TRS483 code of practice for dosimetry of small static fields used in conventional linac beams and comparison with IAEA TRS‐398, AAPM TG51, and TG51 Addendum protocols

PURPOSEnThe International Atomic Energy Agency (IAEA) and the American Association of Physicists in Medicine (AAPM) have jointly published a new code of practice (CoP), TRS483, for the dosimetry of small static photon fields used in external beam radiotherapy. It gave recommendations on how to perform reference dosimetry in nonstandard machine-specific reference (msr) fields and measure field output factors in small fields. The purpose of this work was to perform a dosimetric evaluation of the recommendations given in this CoP.nnnMETHODSnAll measurements were done in a Varian TrueBeam™ STx linear accelerator. Five ionization chambers were used for beam quality measurements, four Farmer type ionization chambers for performing reference dosimetry and two diodes for performing field output factor measurements. Field output factor measurements were done for fourteen field sizes (ranging from 0.5 cm × 0.5 cm to 10 cm × 10 cm). Beam energies used were: 6 MV WFF, 6 MV FFF, 10 MV WFF, and 10 MV FFF. Where appropriate, results from this study were compared with those obtained from the recommendations given in the IAEA TRS398 CoP, AAPM TG51 and TG51 Addendum protocols.nnnRESULTSnBeam quality measurements show that for all beam energies and for equivalent square msr field sizes ranging from 4 cm × 4 cm to 10 cm × 10 cm, agreement between calculated and measured values of TPR20,10 (10) was within 0.6%. When %dd(10,10)X was used as beam quality specifier, the agreement was found to be within 0.8%. Absorbed dose to water per unit monitor unit at the depth of maximum dose zmax in a beam of quality Q, Dw,Qzmax/MU, was determined using both %dd(10,10)X and TPR20,10 (10) as beam quality specifiers. Measured ratios of Dw,Q (zmax )/MU, determined using the two approaches, ranged between 0.999 and 1.000 for all the beam energies investigated. Comparison with TRS398, TG51 and TG51 addendum protocols show that depending on beam energy, the mean values of the ratios TRS398/TRS483, TG51/TRS483, and TG51 Addendum/TRS483 of Dw,Q (zmax )/MU determined using both approaches show excellent agreement with TRS398 CoP (to within 0.05%); agreement with TG51 and TG51 addendum was to within 0.3% for all four beam energies investigated. Field output factors, determined using the two methods recommended in the TRS483 CoP, showed excellent agreement between the two methods. For the 1 cm collimator field size, the mean value of the field output factor obtained from an average of the two detectors investigated was found to be 2% lower than the mean value of the uncorrected ratio of readings.nnnCONCLUSIONnFor beams with and without flattening filters, the values of Dw,Q (zmax )/MU obtained following the new CoP are found to be consistent with those obtained using TRS398, TG51 and TG51 addendum protocols to within 0.3%. Field output factors for small beams can be improved when the correction factors for different detectors included in TRS483 are appropriately incorporated into their dosimetry.

ATR kinase inhibitor AZD6738 potentiates CD8+ T cell-dependent antitumor activity following radiation

DNA-damaging chemotherapy and radiation therapy are integrated into the treatment paradigm of the majority of cancer patients. Recently, immunotherapy that targets the immunosuppressive interaction between programmed death 1 (PD-1) and its ligand PD-L1 has been approved for malignancies including non–small cell lung cancer, melanoma, and head and neck squamous cell carcinoma. ATR is a DNA damage–signaling kinase activated at damaged replication forks, and ATR kinase inhibitors potentiate the cytotoxicity of DNA-damaging chemotherapies. We show here that the ATR kinase inhibitor AZD6738 combines with conformal radiation therapy to attenuate radiation-induced CD8+ T cell exhaustion and potentiate CD8+ T cell activity in mouse models of Kras-mutant cancer. Mechanistically, AZD6738 blocks radiation-induced PD-L1 upregulation on tumor cells and dramatically decreases the number of tumor-infiltrating Tregs. Remarkably, AZD6738 combines with conformal radiation therapy to generate immunologic memory in complete responder mice. Our work raises the possibility that a single pharmacologic agent may enhance the cytotoxic effects of radiation while concurrently potentiating radiation-induced antitumor immune responses.

SU-F-T-652: Verification of Inter-Fractional Tumor Motion Using Daily Fiducial Length Measurement for Pancreatic SBRT

PURPOSEnTo evaluate possible inter-fractional tumor motion variability for pancreatic SBRT with length measurement of the fiducial depiction on the scan and to develop an empirical correlation using a moving phantom and fiducials for adjusting gating window on a daily basis METHODS: In this retrospective study, motion data for fifty pancreatic SBRT patients with fiducials were selected to find the tumor motion statistics. Three gold fiducials of 5mm were placed around a solid target inside the Quasar Phantom and the 4D CT images of the Phantom were acquired with tumor motion of 1cm in superior-inferior direction. The breathing period was set to 4 seconds with a sinusoidal breathing form. After 4D-CT acquisition, CT50% images were imported into the Eclipse and setup fields were created for acquiring CBCT images. CBCT images were acquired by using the TrueBeam-STx and Pelvis technique. For sinusoidal tumor motions, CBCT images were acquired with tumor motion from zero to 2cm with 0.5cm increment along SI direction. The breathing period was varied from 2∼6 seconds with 2-second increment. Also, real patients breathing files acquired from Varian-RPM system were used to simulate real patients breathing patterns. Then length of fiducial depiction was measured with a HU threshold of zero and was used to find its correlation with real tumor motion.nnnRESULTSnTumor motions in SI, AP, and LR directions were 0.7±0.5cm, 0.2±0.3cm, and 0.1±0.2cm, respectively. Breathing period was 4.3±0.8seconds. For a sinusoidal breathing form, there was a significant correlation between length of fiducial and real tumor motions with R2 of 0.98. However, the length of fiducial was independent of varying breathing periods. For a real patients breathing file, the correlation between fiducial length(Y) and tumor motion(X) was Y=1.1268X+0.2696 with R2 of 0.99.nnnCONCLUSIONnWith daily fiducial length measurement, we can evaluate possible changes in the inter-fractional tumor motion in pancreatic SBRT.

SU-D-BRB-07: Use of Knowledge-Based Planning to Evaluate the Need for Motion Management in Lung SBRT

PURPOSEnThe planning margins necessary to safely treat targets in the lung can be reduced depending upon the use of gating or abdominal compression to manage respiratory motion, but these may be uncomfortable for the patient, involve expensive equipment, or increase the length of each treatment fraction. The goal of this project is to use knowledge-based-planning (KBP) to evaluate which patients may benefit most from motion management.nnnMETHODSnThe Varian RapidPlan KBP module was used to estimate doses for VMAT SBRT lung treatment plans with different planning margins corresponding to 1) standard lung setup (1.0 cm radial margin, 2.0 cm S-I margin), 2) daily IGRT (0.7 cm radial 1.5 cm S-I), 3) daily IGRT with motion management (0.5 cm radial, 1.0 cm S-I). The estimated doses were then compared with treatment plan doses (AAA dose calculation) generated using the RapidPlan™ optimization constraints. Treatment plan doses were then compared against RTOG protocol dose limits for organs at risk.nnnRESULTSnThe OAR doses were within or below the estimated range generated by the KBP system in 100% of plans. With standard margins, only 10% of the plans were able to meet all RTOG dose goals, compared with 75% of plans with IGRT margins. All plans were able to meet RTOG dose guidelines with motion management. The DVH estimation was able to correctly identify 100% of the plans in which one or more OAR doses exceeded RTOG guidelines. Also, the dose estimates correctly identified 88% of individual OAR doses exceeding RTOG guidelines.nnnCONCLUSIONnThe KBP system was able to accurately predict the achievable doses in treatment plans, and predict patients in which RTOG dose guidelines would be exceeded. The system may be a useful tool in identifying patients where motion management may be necessary for SBRT treatment. This work was supported by Varian Medical Systems.

SU-E-T-604: Penumbra Characteristics of a New InCiseâ„¢ Multileaf Collimator of CyberKnife M6â„¢ System

Purpose: The InCise™ Multileaf Collimator (MLC) of CyberKnife M6™ System has been released recently. The purpose of this study was to explore the dosimetric characteristics of the new MLC. In particular, the penumbra characteristics of MLC fields at varying locations are evaluated. Methods: EBT3-based film measurements were performed with varying MLC fields ranging from 7.5 mm to 27.5 mm. Seventeen regions of interests (ROIs) were identified for irradiation. These are regions located at the central area (denoted as reference field), at the left/right edge areas of reference open field, at an intermediate location between central and edge area. Single beam treatment plans were designed by using the MultiPlan and was delivered using the Blue Phantom. Gafchromic films were irradiated at 1.5 cm depth in the Blue Phantom and analyzed using the Film Pro software. Variation of maximum dose, penumbra of MLC-defined fields, and symmetry/flatness were calculated as a function of locations of MLC fields. Results: The InCise™ MLC System showed relatively consistent dose distribution and penumbra size with varying locations of MLC fields. The measured maximum dose varied within 5 % at different locations compared to that at the central location and agreed with the calculated data well within 2%.morexa0» The measured penumbrae were in the range of 2.9 mm and 3.7 mm and were relatively consistent regardless of locations. However, dose profiles in the out-of-field and in-field regions varied with locations and field sizes. Strong variation was seen for all fields located at 55 mm away from the central field. The MLC leakage map showed that the leakage is dependent on position. Conclusion: The size of penumbra and normalized maximum dose for MLC-defined fields were consistent in different regions of MLC. However, dose profiles in the out-field region varied with locations and field sizes.«xa0less

SU‐E‐T‐129: Are Knowledge‐Based Planning Dose Estimates Valid for Distensible Organs?

Purpose: Knowledge-based planning programs have become available to assist treatment planning in radiation therapy. Such programs can be used to generate estimated DVHs and planning constraints for organs at risk (OARs), based upon a model generated from previous plans. These estimates are based upon the planning CT scan. However, for distensible OARs like the bladder and rectum, daily variations in volume may make the dose estimates invalid. The purpose of this study is to determine whether knowledge-based DVH dose estimates may be valid for distensible OARs. Methods: The Varian RapidPlan™ knowledge-based planning module was used to generate OAR dose estimates and planning objectives for 10 prostate cases previously planned with VMAT, and final plans were calculated for each. Five weekly setup CBCT scans of each patient were then downloaded and contoured (assuming no change in size and shape of the target volume), and rectum and bladder DVHs were recalculated for each scan. Dose volumes were then compared at 75, 60,and 40 Gy for the bladder and rectum between the planning scan and the CBCTs. Results: Plan doses and estimates matched well at all dose points., Volumes of the rectum and bladder varied widely between planning CT and the CBCTs, ranging from 0.46 to 2.42 for the bladder and 0.71 to 2.18 for the rectum, causing relative dose volumes to vary between planning CT and CBCT, but absolute dose volumes were more consistent. The overall ratio of CBCT/plan dose volumes was 1.02 ±0.27 for rectum and 0.98 ±0.20 for bladder in these patients. Conclusion: Knowledge-based planning dose volume estimates for distensible OARs are still valid, in absolute volume terms, between treatment planning scans and CBCT’s taken during daily treatment. Further analysis of the data is being undertaken to determine how differences depend upon rectum and bladder filling state. This work has been supported by Varian Medical Systems.

SU‐E‐T‐88: Acceptance Testing and Commissioning Measurements of a Newly Released InCiseâ„¢ Multileaf Collimator for CyberKnife M6â„¢ System

Purpose: Accuray recently released a new collimator, the InCise™ Multileaf Collimator (MLC), for clinical use with the CyberKnife M6™ System. This work reports the results of acceptance testing and commissioning measurements for this collimator. Methods: The MLC consists of 41 pairs of 2.5 mm wide leaves projecting a clinical maximum field size of 110 mm x 97.5 mm at 800 mm SAD. The leaves are made of tungsten, 90 mm in height and tilted by 0.5 degree. The manufacturer stated leaf positioning accuracy and reproducibility are 0.5 mm and 0.4 mm respectively at 800 mm SAD. The leaf over-travel is 100% with full interdigitation capability. Acceptance testing included, but are not limited to, the verification of the specifications of various parameters described above, leakage measurements and end-to-end tests. Dosimetric measurements included, but not limited to, measurements of output factors, open beam profiles, tissue-phantom ratios, beam flatness and symmetry, and patient specific QA. Results: All measurements were well within the manufacturer specifications. The values of output factors ranged from 0.804 (smallest field size of 7.6 mm x 7.5 mm) to 1.018 (largest field size of 110.0 mm x 97.5 mm). End-to-end test results for the various tracking modes are: Skull (0.27mm), fiducial (0.16mm), Xsight Spine (0.4mm), Xsight Lung (0.93 mm) and Synchrony (0.43mm). Measured maximum and average leakage was 0.37% and 0.3%, respectively. Patient-specific QA measurements with chamber were all within 5% absolute dose agreement, and film measurements all passed 2%/2mm gamma evaluation for more than 95% of measurement points. Conclusion: The presented results are the first set of data reported on the InCise™ MLC. The MLC proved to be very reliable and is currently in clinical use.