Enhanced Dosimetric Accuracy Using Quality Factor Compensation Method for In Vivo Electron Paramagnetic Resonance Tooth Dosimetry.

ABSTRACT: We aim to develop a dose assessment method compensating for quality factors (Q factor) observed during in vivo EPR tooth dosimetry. A pseudo-in-vivo phantom made of tissue-equivalent material was equipped with one each of four extracted human central incisors. A range of Q factors was measured at tooth-depths of -2, 0, and 2 mm in the pseudo-in-vivo phantom. In addition, in vivo Q factors were measured from nine human volunteers. For the dose-response data, the above four sample teeth were irradiated at 0, 1, 2, 5, and 10 Gy, and the radiation-induced signals were measured at the same tooth-depths using an in vivo EPR tooth dosimetry system. To validate the method, the signals of two post-radiotherapy patients and three unirradiated volunteers were measured using the same system. The interquartile range of the Q factors measured in the pseudo-in-vivo phantom covered that observed from the human volunteers, which implied that the phantom represented the Q factor distribution of in vivo conditions. The dosimetric sensitivities and background signals were decreased as increasing the tooth-depth in the phantom due to the decrease in Q factors. By compensating for Q factors, the diverged dose-response data due to various Q factors were converged to improve the dosimetric accuracy in terms of the standard error of inverse prediction (SEIP). The Q factors of patient 1 and patient 2 were 98 and 64, respectively, while the three volunteers were 100, 92, and 99. The assessed doses of patient 1 and patient 2 were 2.73 and 12.53 Gy, respectively, while expecting 4.43 and 13.29 Gy, respectively. The assessed doses of the unirradiated volunteers were 0.53, 0.50, and - 0.22 Gy. We demonstrated that the suggested Q factor compensation could mitigate the uncertainty induced by the variation of Q factors.

Verification of Low Risk for Perihippocampal Recurrence in Patients with Brain Metastases Who Received Whole-Brain Radiotherapy with Hippocampal Avoidance.

PURPOSE: The purpose of this study was to analyze the patterns of failure and survival outcome in patients with brain metastases who received whole-brain radiotherapy (WBRT) with hippocampal avoidance (HA) using simultaneous integrated boost (SIB) on metastatic brain tumors. MATERIALS AND METHODS: We retrospectively reviewed 42 patients treated with HA-WBRT for brain metastases. A total of 25 Gy for whole brain and 35-55 Gy for gross tumors were delivered with 10 fractionations. Local tumor and intracranial progression were defined as a recurrence or tumor progression in SIB field and any recurrence or tumor progression within whole brain, respectively. Progression in HA zone was defined as the recurrence within the area expanded 5 mm from HA zone. RESULTS: Median follow-up duration was 10.0 months (range, 4.1 to 56.4 months). Intracranial progression was observed in 13 patients (31.0%) and the median duration from the start of HA-WBRT to progression was 10.6 months (range, 0.9 to 33.0 months). Local tumor progression and new metastasis outside SIB field occurred in 10 patients (23.8%) and nine patients (21.4%), respectively. There was no isolated hippocampal metastasis, except only one patient (2.4%) with multiple metastases inside and outside HA zone simultaneously. Median survival time and intracranial progression-free survival rate at 1 year were 19.4 months (95% confidence interval [CI], 9.6 to 29.2) and 71.5%, respectively, and those for overall survival were 26.5 months (95% CI, 15.4 to 37.5) and 67.9%, respectively. CONCLUSION: HA-WBRT was associated with low risk of new metastasis in HA region in the patients with brain metastases. These findings would serve as useful guidance on applying HA-WBRT in clinical practice.

Treatment outcome of diffuse large B-cell lymphoma involving the head and neck: Two-institutional study for the significance of radiotherapy after R-CHOP chemotherapy.

This study was performed to analyze the treatment outcome for diffuse large B-cell lymphoma (DLBCL) involving the head and neck and to evaluate the role of radiotherapy in the rituximab era. Fifty-six patients diagnosed with DLBCL involving the head and neck were assessed. All patients were treated with 6 cycles of rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone (R-CHOP). After chemotherapy, radiation was delivered to the head and neck area in a median dose of 36 Gy. Radiation was delivered using 3-dimensional radiotherapy (n  =  25) or intensity-modulated radiotherapy (n  =  31). Primary endpoints were relapse-free survival (RFS), overall survival (OS), and local control rate. After median follow-up time of 45 months, the 5-year RFS and OS rates were 72% and 61%, respectively. Fourteen (25%) of 56 patients relapsed; 1 had a local relapse, 11 had distant relapses, and 2 had both local and distant relapses. The final local control rate after radiotherapy was 94%. Age, performance status, international prognostic index score, and radiotherapy response were significant prognostic factors for both RFS and OS in the multivariate analysis. Incidence of acute grade 3 and 4 hematologic toxicity was 9% and 4%, respectively. Grade 3 nonhematologic toxicity occurred in 2 (4%) patients, and there was no grade 4 nonhematologic toxicity for the irradiated patients. Excellent local control and survival rates can be achieved with R-CHOP followed by radiotherapy in patients with DLBCL involving the head and neck. Treatment-related toxicity after the introduction of modern radiotherapy was acceptable and limited.

Analysis of Geometric Shifts and Proper Setup-Margin in Prostate Cancer Patients Treated With Pelvic Intensity-Modulated Radiotherapy Using Endorectal Ballooning and Daily Enema for Prostate Immobilization.

We evaluate geometric shifts of daily setup for evaluating the appropriateness of treatment and determining proper margins for the planning target volume (PTV) in prostate cancer patients.We analyzed 1200 sets of pretreatment megavoltage-CT scans that were acquired from 40 patients with intermediate to high-risk prostate cancer. They received whole pelvic intensity-modulated radiotherapy (IMRT). They underwent daily endorectal ballooning and enema to limit intrapelvic organ movement. The mean and standard deviation (SD) of daily translational shifts in right-to-left (X), anterior-to-posterior (Y), and superior-to-inferior (Z) were evaluated for systemic and random error.The mean ±â€ŠSD of systemic error (Σ) in X, Y, Z, and roll was 2.21 ±â€Š3.42 mm, -0.67 ±â€Š2.27 mm, 1.05 ±â€Š2.87 mm, and -0.43 ±â€Š0.89°, respectively. The mean ±â€ŠSD of random error (δ) was 1.95 ±â€Š1.60 mm in X, 1.02 ±â€Š0.50 mm in Y, 1.01 ±â€Š0.48 mm in Z, and 0.37 ±â€Š0.15° in roll. The calculated proper PTV margins that cover >95% of the target on average were 8.20 (X), 5.25 (Y), and 6.45 (Z) mm. Mean systemic geometrical shifts of IMRT were not statistically different in all transitional and three-dimensional shifts from early to late weeks. There was no grade 3 or higher gastrointestinal or genitourianry toxicity.The whole pelvic IMRT technique is a feasible and effective modality that limits intrapelvic organ motion and reduces setup uncertainties. Proper margins for the PTV can be determined by using geometric shifts data.

Setup Error and Effectiveness of Weekly Image-Guided Radiation Therapy of TomoDirect for Early Breast Cancer.

PURPOSE: This study investigated setup error and effectiveness of weekly image-guided radiotherapy (IGRT) of TomoDirect for early breast cancer. MATERIALS AND METHODS: One hundred and fifty-one breasts of 147 consecutive patients who underwent breast conserving surgery followed by whole breast irradiation using TomoDirect in 2012 and 2013 were evaluated. All patients received weekly IGRT. The weekly setup errors from simulation to each treatment in reference to chest wall and surgical clips were measured. Random, systemic, and 3-dimensional setup errors were assessed. Extensive setup error was defined as 5 mm above the margin in any directions. RESULTS: All mean errors were within 3 mm of all directions. The mean angle of gantry shifts was 0.6°. The mean value of absolute 3-dimensional setup error was 4.67 mm. In multivariate analysis, breast size (odds ratio, 2.82; 95% confidence interval, 1.00 to 7.90) was a significant factor for extensive error. The largest significant deviation of setup error was observed in the first week of radiotherapy (p < 0.001) and the deviations gradually decreased with time. The deviation of setup error was 5.68 mm in the first week and within 5 mm after the second week. CONCLUSION: In this study, there was a significant association between breast size and significant setup error in breast cancer patients who received TomoDirect. The largest deviation occurred in the first week of treatment. Therefore, patients with large breasts should be closely observed on every fraction and fastidious attention is required in the first fraction of IGRT.

Evaluation of the Flash effect in breast irradiation using TomoDirect: an investigational study.

Flash is a specified function in TomoDirect that enables beam expansion by opening additional leaves to the target. This study assessed the theoretical dose distribution resulting from Flash in breast irradiation using TomoDirect. A cylindrical phantom that enabled dose distribution of the breast was used for verifying the effect of planning target volume (PTV) contouring and Flash. A total of 18 Gy in 10 fractions were prescribed to the PTV. Five PTVs were then created by Contracting this contour by 0, 1, 2, 3, 4 and 5 mm, giving PTV-x. Flash ±x is defined by opening x (number) of the leaves. The Flash effect in the air was compared with each set-up error of 5, 10 and 15 mm, respectively. The minimum PTV dose from PTV-1 to PTV-3 increased from 13.88 Gy to 15.86 Gy. In contrast, Dmin in PTV-4 and PTV-5 was 17.80 Gy in 98.88% of the prescription dose. Without Flash, when 5-, 10- and 15-mm set-up errors applied in the PTV, relative doses of 87.88, 23.73 and 7.94% were observed, respectively. However, in Flash 3, which was equal to the usual air margin of 1.875 cm, a relative dose of 104.24% ± 0.30% was observed, irrespective of set-up errors (5 mm to 15 mm). Flash opening is useful for countervailing set-up errors in breast cancer patients who receive breast irradiation with TomoDirect.

A prospective cohort study on postoperative radiotherapy with TomoDirect using simultaneous integrated boost technique in early breast cancer.

PURPOSE: To evaluate the technical feasibility and toxicity of TomoDirect in breast cancer patients who received radiotherapy after breast-conserving surgery. METHODS: 155 consecutive patients with breast carcinoma in situ or T1-2 breast cancer with negative lymph node received breast irradiation with TomoDirect using simultaneous integrated boost technique in the prospective cohort study. A radiation dose of 50.4 Gy and 57.4 Gy in 28 fractions was prescribed to the ipsilateral breast and tumor bed, respectively. Dosimetric parameters of target and organ at risk and acute complication were assessed prospectively. RESULTS: The mean dose for the tumor bed is 58.90 Gy. The mean values of V54.53Gy (95% of the prescribed dose), V63.14Gy (110% of the prescribed dose), and V66.01Gy (115% of the prescribed dose) were 99.97%, 1.26%, and 0%, respectively. The mean value of radiation conformality index was 1.01. The mean value of radical dose homogeneity index was 0.89. The average dose irradiated to the ipsilateral lung, heart, and contralateral breast was 4.72 Gy, 1.09 Gy, and 0.19 Gy, respectively. The most common toxicity was dermatitis. During breast irradiation, grade 2 and 3 dermatitis occurred in 41 (26.5%) and 6 (3.9%) of the 155 patients, respectively. Two patients had arm lymphedema during breast irradiation. Two patients had grade 2 pneumonitis 1 month after breast irradiation. CONCLUSIONS: Radiotherapy using TomoDirect in early breast cancer patients showed acceptable toxicities and optimal results in terms of target coverage and organ at risk sparing.

Hypofractionated radiotherapy with tomotherapy for patients with hepatic oligometastases: retrospective analysis of two institutions.

To evaluate the efficacy and toxicity for patients with hepatic oligometastases, receiving hypofractionated radiotherapy with Tomotherapy to the liver. A total of 42 patients with 54 hepatic lesions, who had been treated from 2007 to 2011 at two institutions, were retrospectively reviewed for this study. All the patients received radical resections of the primary tumor, and had been presented with one to two hepatic lesions. The radiation dose of 40-75 Gy in 10-20 fractions (median, 50 Gy in 10 fractions) was delivered for the planning target volume. At a median follow-up time of 15 months, 1- and 2-year local control (LC) rates were 59.9 and 49.0 %, respectively. The 1- and 2-year overall survival (OS) rates were 60.0 and 44.0 %, respectively. Maximal tumor diameter of <3 cm and biologically effective dose (BED) of ≥100 Gyα/ß=10 were significantly associated with higher LC and OS. Primary colorectal cancer tended to be associated with higher LC (P = 0.075), and was significantly associated with higher OS (P = 0.037). 12 (28.6 %) of the 42 patients had grade 1-2 toxicities, and grade 3 or higher toxicity did not occur. Hypofractionated radiotherapy with Tomotherapy was safe for patients with hepatic oligometastases. The maximal tumor diameter of <3 cm and BED of ≥100 Gyα/ß=10 were significant prognostic factors for higher local control and survival, and primary colorectal cancer patients had statistically higher overall survival than the others.

Tumor bed volumetric changes during breast irradiation for the patients with breast cancer.

PURPOSE: The aim of this study was to evaluate changes in breast tumor bed volume during whole breast irradiation (WBI). MATERIALS AND METHODS: From September 2011 to November 2012, thirty patients who underwent breast-conserving surgery (BCS) followed by WBI using computed tomography (CT) simulation were enrolled. Simulation CT scans were performed before WBI (CT1) and five weeks after the breast irradiation (CT2). The tumor bed was contoured based on surgical clips, seroma, and postoperative change. We retrospectively analyzed the factors associated with tumor bed volumetric change. RESULTS: The median tumor bed volume on CT1 and CT2 was 29.72 and 28.6 mL, respectively. The tumor bed volume increased in 9 of 30 patients (30%) and decreased in 21 of 30 patients (70%). The median percent change in tumor bed volume between initial and boost CT was -5%. Seroma status (p = 0.010) was a significant factor in tumor bed volume reduction of 5% or greater. However, patient age, body mass index, palpability, T stage, axillary lymph node dissection, and tumor location were not significant factors for tumor bed volumetric change. CONCLUSION: In this study, volumetric change of tumor bed cavity was frequent. Patients with seroma after BCS had a significant volume reduction of 5% or greater in tumor bed during breast irradiation. Thus, resimulation using CT is indicated for exquisite boost treatment in breast cancer patients with seroma after surgery.