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

Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.
International journal of radiation oncology, biology, physics (Impact Factor: 4.26). 04/2011; 82(5):1619-26. DOI: 10.1016/j.ijrobp.2011.01.050
Source: PubMed


To investigate the interfractional dose variations for intensity-modulated radiotherapy (RT) combined with breath-hold (BH) at end-exhalation (EE) for pancreatic cancer.
A 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 = GTV + 5 mm), stomach, and duodenum were evaluated.
For 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.
Despite 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.

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    ABSTRACT: Purpose: This 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. Methods: Thirty 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. Results: Substantial 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. Conclusions: Considerable 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.
    Medical Physics 02/2013; 40(2):021701. DOI:10.1118/1.4773033 · 2.64 Impact Factor
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    ABSTRACT: In patients with pancreatic cancer, intensity-modulated radiotherapy (IMRT) under breath holding facilitates concentration of the radiation dose in the tumor, while sparing the neighboring organs at risk and minimizing interplay effects between movement of the multileaf collimator and motion of the internal structures. Although the breath-holding technique provides high interportal reproducibility of target position, dosimetric errors caused by interportal breath-holding positional error have not been reported. Here, we investigated the effects of interportal breath-holding positional errors on IMRT dose distribution by incorporating interportal positional error into the original treatment plan, using random numbers in ten patients treated for pancreatic cancer. We also developed a treatment planning technique that shortens breath-holding time without increasing dosimetric quality assurance workload. The key feature of our proposed method is performance of dose calculation using the same optimized fluence map as the original plan, after dose per fraction in the original plan was cut in half and the number of fractions was doubled. Results confirmed that interportal error had a negligible effect on dose distribution over multiple fractions. Variations in the homogeneity index and the dose delivered to 98%, 2%, and 50% of the volume for the planning target volume, and the dose delivered to 1 cc of the volume for the duodenum and stomach were ±1%, on average, in comparison with the original plan. The new treatment planning method decreased breath-holding time by 33%, and differences in dose-volume metrics between the original and the new treatment plans were within ± 1%. An additional advantage of our proposed method is that interportal errors can be better averaged out; thus, dose distribution in the proposed method may be closer to the planned dose distribution than with the original plans.
    Journal of Applied Clinical Medical Physics 09/2013; 14(5):4252. · 1.17 Impact Factor
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    ABSTRACT: We assessed interfraction positional variation in pancreatic tumors using daily breath-hold cone-beam computed tomography at end-exhalation (EE) with visual feedback (BH-CBCT). Eleven consecutive patients with pancreatic cancer who underwent BH intensity-modulated radiation therapy with visual feedback were enrolled. All participating patients stopped oral intake, with the exception of drugs and water, for > 3 hr before treatment planning and daily treatment. Each patient was fixed in the supine position on an individualized vacuum pillow. An isotropic margin of 5 mm was added to the clinical target volume to create the planning target volume (PTV). The prescription dose was 42 to 51 Gy in 15 fractions. After correcting initial setup errors based on bony anatomy, the first BH-CBCT scans were performed before beam delivery in every fraction. BH-CBCT acquisition was obtained in three or four times breath holds by interrupting the acquisition two or three times, depending on the patient's BH ability. The image acquisition time for a 360° gantry rotation was approximately 90 s, including the interruption time due to BH. The initial setup errors were corrected based on bony structure, and the residual errors in the target position were then recorded. The magnitude of the interfraction variation in target position was assessed for 165 fractions. The systematic and random errors were 1.2 and 1.8 mm, 1.1 and 1.8 mm, and 1.7 and 2.9 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. Absolute interfraction variations of > 5 mm were observed in 18 fractions (11.0%) from seven patients because of EE-BH failure. In conclusion, target matching is required to correct interfraction variation even with visual feedback, especially to ensure safe delivery of escalated doses to patients with pancreatic cancer.
    Journal of Applied Clinical Medical Physics 06/2015; 16(2):5123. DOI:10.1120/jacmp.v16i2.5123 · 1.17 Impact Factor