Takehiro Shiinoki

Analysis of Dosimetric Parameters Associated With Acute Gastrointestinal Toxicity and Upper Gastrointestinal Bleeding in Locally Advanced Pancreatic Cancer Patients Treated With Gemcitabine-Based Concurrent Chemoradiotherapy

PURPOSEnTo identify the dosimetric parameters associated with gastrointestinal (GI) toxicity in patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based chemoradiotherapy.nnnMETHODS AND MATERIALSnThe data from 40 patients were analyzed retrospectively. Chemoradiotherapy consisted of conventional fractionated three-dimensional radiotherapy and weekly gemcitabine. Treatment-related acute GI toxicity and upper GI bleeding (UGB) were graded according to the Common Toxicity Criteria Adverse Events, version 4.0. The dosimetric parameters (mean dose, maximal absolute dose which covers 2 cm(3) of the organ, and absolute volume receiving 10-50 Gy [V(10-50)]) of the stomach, duodenum, small intestine, and a composite structure of the stomach and duodenum (StoDuo) were obtained. The planning target volume was also obtained. Univariate analyses were performed to identify the predictive factors for the risk of grade 2 or greater acute GI toxicity and grade 3 or greater UGB, respectively.nnnRESULTSnThe median follow-up period was 15.7 months (range, 4-37). The actual incidence of acute GI toxicity was 33%. The estimated incidence of UGB at 1 year was 20%. Regarding acute GI toxicity, a V(50) of ≥ 16 cm(3) of the stomach was the best predictor, and the actual incidence in patients with V(50) <16 cm(3) of the stomach vs. those with V(50) of ≥ 16 cm(3) was 9% vs. 61%, respectively (p = 0.001). Regarding UGB, V(50) of ≥ 33 cm(3) of the StoDuo was the best predictor, and the estimated incidence at 1 year in patients with V(50) <33 cm(3) of the StoDuo vs. those with V(50) ≥ 33 cm(3) was 0% vs. 44%, respectively (p = 0.002). The dosimetric parameters correlated highly with one another.nnnCONCLUSIONnThe irradiated absolute volume of the stomach and duodenum are important for the risk of acute GI toxicity and UGB. These results could be helpful in escalating the radiation doses using novel techniques, such as intensity-modulated radiotherapy, for the treatment of pancreatic cancer.

Positional reproducibility of pancreatic tumors under end-exhalation breath-hold conditions using a visual feedback technique

PURPOSEnTo assess positional reproducibility of pancreatic tumors under end-exhalation (EE) breath-hold (BH) conditions with a visual feedback technique based on computed tomography (CT) images.nnnMETHODS AND MATERIALSnTen patients with pancreatic cancer were enrolled in an institutional review board-approved trial. All patients were placed in a supine position on an individualized vacuum pillow with both arms raised. At the time of CT scan, they held their breath at EE with the aid of video goggles displaying their abdominal displacement. Each three-consecutive helical CT data set was acquired four times (sessions 1-4; session 1 corresponded to the time of CT simulation). The point of interest within or in proximity to a gross tumor volume was defined based on certain structural features. The positional variations in point of interest and margin size required to cover positional variations were assessed.nnnRESULTSnThe means ± standard deviations (SDs) of intrafraction positional variations were 0.0 ± 1.1, 0.1 ± 1.2, and 0.1 ± 1.0 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively (p = 0.726). The means ± SDs of interfraction positional variations were 0.3 ± 2.0, 0.8 ± 1.8, and 0.3 ± 1.8 mm in the LR, AP, and SI directions, respectively (p = 0.533). Population-based margin sizes required to cover 95th percentiles of the overall positional variations were 4.7, 5.3, and 4.9 mm in the LR, AP, and SI directions, respectively.nnnCONCLUSIONSnA margin size of 5 mm was needed to cover the 95th percentiles of the overall positional variations under EE-BH conditions, using this noninvasive approach to motion management for pancreatic tumors.

Interfractional Reproducibility in Pancreatic Position Based on Four-Dimensional Computed Tomography

PURPOSEnTo assess the interfractional positional variation of the pancreas using four-dimensional computed tomography (4D-CT) and to determine the suitable phase of respiration for dose delivery methods to account for pancreatic tumor motion.nnnMETHODS AND MATERIALSnFifteen patients with pancreatic cancer were enrolled in this study. For each patient, 4D-CT scans were performed at CT simulation and three times during the course of treatment. Regions of interest were set to the intrapancreatic bile ducts as a surrogate for pancreatic position. The centroids of the regions of interest were calculated at end-inhalation and end-exhalation of the respiration phase. The ranges of respiratory motion and interfractional positional variation were evaluated in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions.nnnRESULTSnThe medians of respiratory motion were 1.1 mm (range, 0.0-9.8 mm), 1.5 mm (range, 0.0-7.0 mm), and 5.0 mm (range, 0.0-12.5 mm) in the LR, AP, and SI directions, respectively. The means ± SDs of the interfractional positional variation at end-inhalation were 0.9 ± 5.1 mm (range, -9.2 to 15.6 mm), -1.9 ± 3.9 mm (range, -12.8 to 6.4 mm), and -1.3 ± 6.9 mm (range, -15.0 to 13.7 mm) and those at end-exhalation were 0.0 ± 3.1 mm (range, -7.0 to 5.3 mm), -1.2 ± 3.9 mm (range, -11.2 to 6.7 mm), and 0.1 ± 3.2 mm (range, -9.9 to 5.1 mm) in the LR, AP, and SI directions, respectively. The SDs of the interfractional positional variation in the LR and SI directions were significantly larger at end-inhalation than at end-exhalation (LR, p < 0.001; SI, p < 0.001).nnnCONCLUSIONSnThe ranges of respiratory motion during the course of treatment and the interfractional positional variation were not negligible. The interfractional positional reproducibility was higher at end-exhalation than at end-inhalation under free breathing.

Interfractional Dose Variations in Intensity-Modulated Radiotherapy With Breath-Hold for Pancreatic Cancer

PURPOSEnTo investigate the interfractional dose variations for intensity-modulated radiotherapy (RT) combined with breath-hold (BH) at end-exhalation (EE) for pancreatic cancer.nnnMETHODS AND MATERIALSnA total of 10 consecutive patients with pancreatic cancer were enrolled. Each patient was fixed in the supine position on an individualized vacuum pillow with both arms raised. Computed tomography (CT) scans were performed before RT, and three additional scans were performed during the course of chemoradiotherapy using a conventional RT technique. The CT data were acquired under EE-BH conditions (BH-CT) using a visual feedback technique. The intensity-modulated RT plan, which used five 15-MV coplanar ports, was designed on the initial BH-CT set with a prescription dose of 39 Gy at 2.6 Gy/fraction. After rigid image registration between the initial and subsequent BH-CT scans, the dose distributions were recalculated on the subsequent BH-CT images under the same conditions as in planning. Changes in the dose-volume metrics of the gross tumor volume (GTV), clinical target volume (CTV = GTVxa0+ 5 mm), stomach, and duodenum were evaluated.nnnRESULTSnFor the GTV and clinical target volume (CTV), the 95th percentile of the interfractional variations in the maximal dose, mean dose, dose covering 95% volume of the region of structure, and percentage of the volume covered by the 90% isodose line were within ±3%. Although the volume covered by the 39 Gy isodose line for the stomach and duodenum did not exceed 0.1 mL at planning, the volume covered by the 39 Gy isodose line for these structures was up to 11.4 cm(3) and 1.8 cm(3), respectively.nnnCONCLUSIONSnDespite variations in the gastrointestinal state and abdominal wall position at EE, the GTV and CTV were mostly ensured at the planned dose, with the exception of 1 patient. Compared with the duodenum, large variations in the stomach volume receiving high-dose radiation were observed, which might be beyond the negligible range in achieving dose escalation with intensity-modulated RT combined with BH at EE.

Interfractional dose variations in the stomach and the bowels during breathhold intensity‐modulated radiotherapy for pancreatic cancer: Implications for a dose‐escalation strategy

PURPOSEnThis study aims to evaluate the interfractional dose variations in the organs-at-risk (OARs) during pancreatic breathhold intensity-modulated radiotherapy (IMRT) and to assess the impacts of planning organs-at-risk volume (POV) structures generated by isotropically expanding the dose-limiting OARs, based on the comparison of the interfractional doses to the OARs between IMRT plans and conventional three-dimensional-conformal radiotherapy (3D-CRT) plans.nnnMETHODSnThirty repeat CT scans were acquired from ten consecutive patients who were receiving chemoradiotherapy for pancreatic cancer. Six IMRT plans for each patient with two levels of prescription (45 and 51 Gy in 15 fractions) and 3 POV margin sizes (5, 7, and 10 mm) were generated based on the initial CT scan under predetermined constraints. Two 3D-CRT plans (39 and 42 Gy in 15 fractions) were simultaneously generated. The dose distribution of all of the treatment plans was recalculated with the repeat CT scans. The interfractional dose variations in the three OARs (stomach, duodenum, and small intestine) were evaluated, and the absolute volumes ≥39 Gy (V39Gy) of the OARs in the IMRT plans were compared to those in the 3D-CRT plans. Regression analyses were performed to assess the relative impact of the factors of interest on the interfractional dose variations of the OARs.nnnRESULTSnSubstantial dose excesses to the three OARs were observed at all of the prescription dose levels and the POV margin sizes on the repeat CT scans. The safety threshold based on the mean stomach V39Gy on the recalculated 39 Gy-3D-CRT plans was 1.9 ml. Statistically significant and marginally insignificant mean V39Gy values above the safety thresholds were observed in the stomach in the 51 Gy-IMRT plans (2.6 and 2.1 ml with the 5- and 7-mm PRV margins, respectively (P = 0.015 and 0.085)). Only in the case of the 10-mm POV margin did the metric fall below the safety threshold to 1.5 ml (P = 0.634). The duodenum and the small intestine did not violate the safety thresholds (1.4 and 3.8 ml, respectively). From the multiple regression analyses, only the margin size (P < 0.001) and the POV V39Gy (P < 0.001) were significantly associated with the distribution of recalculated V39Gy for the stomach. Multiple factors, including the margin size (P = 0.020) and the POV V39Gy (P < 0.001) were associated with the recalculated V39Gy for the duodenum. However, none of the POV parameters for the small intestine were associated with the recalculated V39Gy.nnnCONCLUSIONSnConsiderable interfractional dose variation was observed in three critical OARs. At the escalated prescription dose of breathhold IMRT, the dose variations could exceed the dose variations using 3D-CRT at the safe prescription dose level, indicating that a dose-escalation strategy based solely on the initial advantageous dose distribution in a breathhold IMRT can be problematic. Given the current limitations for predicting or coping with variation throughout the treatment course, the use of POV should be considered for safely delivering escalated doses to patients with pancreatic cancer.

Dosimetric investigation of breath-hold intensity-modulated radiotherapy for pancreatic cancer

PURPOSEnTo experimentally investigate the effects of variations in respiratory motion during breath-holding (BH) at end-exhalation (EE) on intensity-modulated radiotherapy (BH-IMRT) dose distribution using a motor-driven base, films, and an ionization chamber.nnnMETHODSnMeasurements were performed on a linear accelerator, which has a 120-leaf independently moving multileaf collimator with 5-mm leaf width at the isocenter for the 20-cm central field. Polystyrene phantoms with dimensions of 40u2009×u200940u2009×u200910 cm were set on a motor-driven base. All gantry angles of seven IMRT plans (a total of 35 fields) were changed to zero, and doses were then delivered to a film placed at a depth of 4 cm and an ionization chamber at a depth of 5 cm in the phantom with a dose rate of 600 MU/min under the following conditions: pulsation from the abdominal aorta and baseline drift with speeds of 0.2 mm/s (BD(0.2mm/s)) and 0.4 mm/s (BD(0.4mm/s)). As a reference for comparison, doses were also delivered to the chamber and film under stationary conditions.nnnRESULTSnIn chamber measurements, meansu2009±u2009standard deviations of the dose deviations between stationary and moving conditions were -0.52%u2009±u20091.03% (range: -3.41-1.05%), -0.07%u2009±u20091.21% (range: -1.88-4.31%), and 0.03%u2009±u20091.70% (range: -2.70-6.41%) for pulsation, BD(0.2mm/s), and BD(0.4mm/s), respectively. The γ passing rate ranged from 99.5% to 100.0%, even with the criterion of 2%/1 mm for pulsation pattern. In the case of BD(0.4mm/s), the γ passing rate for four of 35 fields (11.4%) did not reach 90% with a criterion of 3%/3 mm. The differences in γ passing rate between BD(0.2mm/s) and BD(0.4mm/s) were statistically significant for each criterion. Taking γ passing rates ofu2009>u200990% as acceptable with a criterion of 3%/3 mm, large differences were observed in the γ passing rate between the baseline drift of ≤5 mm and that of >5 mm (minimum γ passing rate: 92.0% vs 82.7%; pu2009<u20090.01).nnnCONCLUSIONSnThis study suggested that the baseline drift of >5 mm should be avoided in the BH-IMRT.

TH-D-210A-09: Correlation Between Abdominal Organ Motion and An External Marker Toward Respiratory-Gated Intensity-Modulated Radiation Therapy for Pancreatic Carcinoma

Purpose: To attain the respiratory‐gated intensity‐modulated radiotherapy(IMRT) for pancreatic carcinoma by using an external marker as a surrogate for tumor motion, the correlation between a motion of an external marker and displacement of a stent around pancreas was investigated. Methods and Materials: Three patients who had undergone the ERCP for biliary decompression with placement of a stent were applied in this study. An anterior‐posterior motion of an external marker placed on the patients abdomen was monitored by the Varian® RPM system for two minutes, this was synchronously displayed on the X‐ray fluoroscopic screen which acquired the stents superior‐inferior displacement. For each patient, the above measurement was performed at four sessions during the treatment course. Both the displacements of an abdominal marker and a stent were automatically extracted by in‐house software based on the template‐matching algorithm. The cross‐correlation coefficients between displacement of an abdominal marker and a stent motion and their intra‐fractional variations were evaluated. The predicted stent positions at 30%, 40% and 50% of respiratory phase, which were traced the regression line from 0%‐phase (Exhalation), were compared with actual positions. Results: The correlation coefficients ( R 2 ) ranged from 0.77 to 0.97 and were inter‐fractionally reproducible. The predicted stents positions at 30 %, 40 % and 50 % of respiratory phase were discrepant with actual positions with errors of 1.6 mm, 2.0 mm and 2.1 mm on average, respectively. Conclusions: The strong correlation between a motion of an external marker and a displacement of a stent around the pancreas was observed with a high reproducibility. An error of the predicted target position by an external marker was up to 3.1 mm for the expected‐gating duration (∼50 % respiratory phase) Our study demonstrated that the respiratory‐gated IMRT for pancreatic carcinoma may be clinically acceptable.

Dosimetric impact of gold markers implanted closely to lung tumors: a Monte Carlo simulation.

We are developing an innovative dynamic tumor tracking irradiation technique using gold markers implanted around a tumor as a surrogate signal, a real‐time marker detection system, and a gimbaled X‐ray head in the Vero4DRT. The gold markers implanted in a normal organ will produce uncertainty in the dose calculation during treatment planning because the photon mass attenuation coefficient of a gold marker is much larger than that of normal tissue. The purpose of this study was to simulate the dose variation near the gold markers in a lung irradiated by a photon beam using the Monte Carlo method. First, the single‐beam and the opposing‐beam geometries were simulated using both water and lung phantoms. Subsequently, the relative dose profiles were calculated using a stereotactic body radiotherapy (SBRT) treatment plan for a lung cancer patient having gold markers along the anteriorposterior (AP) and right‐left (RL) directions. For the single beam, the dose at the gold marker‐phantom interface laterally along the perpendicular to the beam axis increased by a factor of 1.35 in the water phantom and 1.58 in the lung phantom, respectively. Furthermore, the entrance dose at the interface along the beam axis increased by a factor of 1.63 in the water phantom and 1.91 in the lung phantom, while the exit dose increased by a factor of 1.00 in the water phantom and 1.12 in the lung phantom, respectively. On the other hand, both dose escalations and dose de‐escalations were canceled by each beam for opposing portal beams with the same beam weight. For SBRT patient data, the dose at the gold marker edge located in the tumor increased by a factor of 1.30 in both AP and RL directions. In clinical cases, dose escalations were observed at the small area where the distance between a gold marker and the lung tumor was ≤ 5 mm, and it would be clinically negligible in multibeam treatments, although further investigation may be required. PACS number: 87.10.Rt

SU‐E‐J‐142: Gafchromic Film Dosimetry in Fluoroscopy for Dynamic Tumor Tracking Irradiation of the Lung Using XR‐SP2 Model ‐ A Phantom Study ‐

PURPOSEnWe have recently developed a dynamic tumor tracking irradiation system using Vero4DRT (MHI-Tm2 000). It is needed to create a 4D correlation model between a fiducial marker implanted near a tumor and an external surrogate as a function of time by continuously acquiring both fluoroscopy images and external surrogate signals. The purpose of this study was to propose a new dosimetry method using Gafchromic XR-SP2 films to measure surface dose by fluoroscopy imaging.nnnMETHODSnFirst, half-value layers (HVLs) were measured using aluminum (Al) thicknesses (15 mm) at 40125 kVp. Subsequently, several films were irradiated using various milliampere second values on a solid water phantom. The surface air kerma were also measured using the chamber to calculate the surface doses under the same condition. Then, the calibration curve of dose vs. pixel values was calculated. Finally, surface dose by fluoroscopy imaging was measured using several pieces of film taped on the chest phantom. Orthogonal X-ray fluoroscopy imaging was simultaneously performed until completion of data acquisition for creating a 4D correlation model. Those films were scanned after irradiation using a flat-bed scanner and converted to dose by calibration curve.nnnRESULTSnThe HVLs for tube voltage within 40125 kVp ranged from 2.35 to 5.98 mm Al. The calibration curve between surface dose and pixel values was reasonably smooth. The differences between the measured and the calibrated doses were less than 3%. The hot spots with the maximum dose of 37.12 mGy were observed around the area overlapped by both fluoroscopic fields.nnnCONCLUSIONSnWe have proposed a new dosimetry method using Gafchromic XR-SP2 films to measure surface dose by fluoroscopy imaging. This phantom study has demonstrated that it may be feasible to assess surface dose to patients during dynamic tumor tracking irradiation in clinic with ease after further investigation. This research was supported by the Japan Society for the Promotion of Science (JSPS) through its Funding Program for World-Leading Innovation R&D on Science and Technology (FIRST Program). Research sponsored in part by Mitsubishi Heavy Industries, Ltd.

SU‐E‐T‐339: First Evaluation of Intensity Modulated Radiation Therapy (IMRT) Delivery Accuracy during Real‐Time Tracking Using a Gimbaled X‐Ray Head of Vero4DRT (MHI‐TM2000)

Purpose: To evaluate the accuracy of intensity modulated radiation therapy(IMRT)delivery during real‐time tumor tracking using a gimbaled X‐ray head of Vero4DRT (MHI‐Tm2000) (Mitsubishi Heavy Industries, Ltd., Japan). Methods: We have utilized a QUASAR platform phantom (Modus Medical Devices Inc.) where a Kodak EDR2 X‐ray film was placed at 5 cm depth in a solid water phantom. A simple step‐and‐shoot test field with five segmental fields and a clinical field for a prostate IMRT were used. Films were irradiated in following three setups: (1) stationary phantom and gimbal, (2) moving phantom and stationary gimbal and (3) moving phantom and real‐time tracking irradiation. The moving phantom was driven by sine waves at a frequency of 0.25, 0.33 and 0.5 Hz with amplitude of 20 mm along tilt direction. 2D dose distributions and profiles were obtained for each case and analyzed using doseanalysis software, DD‐IMRT (R‐TECH.INC, Japan). Results: We observed a large dose blurring effect and as large as 40% dose discrepancies between (1) and (2) for the test field at the high dose gradient. In contrast, the comparison of (1) with (3) shows the differences less than 3% in the most area except the high dose gradient. We also found the good agreement between (1) and (3) for a clinical field. The percentage of values of discrepancy less than 5% and 3% were 97.5% and 82.0%, respectively. Conclusions: We demonstrated the significant dose blurring effect with a moving target in step‐and‐shoot IMRTdosedelivery and it was greatly improved by real‐time tumor tracking with Vero4DRT. The system showed an excellent accuracy of IMRTdosedelivery during tumor tracking as Result of the first evaluation. This research was supported by the Japan Society for the Promotion of Science (JSPS) through its Funding Program for World‐Leading Innovation R&D on Science and Technology (FIRST Program). Research sponsored in part by Mitsubishi Heavy Industries, Ltd.