Radiation induced brain injury: assessment of white matter tracts in a pre-clinical animal model using diffusion tensor MR imaging.

We aim to study radiation induced white matter injury in a pre-clinical model using Diffusion tensor MR imaging (DTI). Nineteen 12-week old Sprague-Dawley rats were irradiated to the right hemisphere using a linear accelerator. The dose distribution map was coregistered to the DTI map to generate the actual radiation dose to each white matter tract. Rats underwent longitudinal DTI scans at five time points from 4 to 48 weeks post-radiation with histological evaluations. Fractional anisotropy (FA) of the external capsule, fornix, cerebral peduncle, anterior commissure, optic tract and optic nerve was evaluated. Radiation dose was highest at the ipsilateral external capsule and fornix (29.4 ± 1.3 and 29.8 ± 1.1 Gy, respectively). Optic nerve received 50 % dose to the external capsule and other white matter tracts received 80 % dose. Significantly lower FA was firstly found in the ipsilateral external capsule at 4 weeks post-radiation and in the ipsilateral fornix at 40 weeks post-radiation compared to the contralateral side. Significantly lower FA was found in contralateral optic nerve compared to ipsilateral optic nerve at 48 weeks post-radiation despite ipsilateral optic nerves receiving higher radiation dose than contralateral optic nerve (p = 0.021). No differences were found in other white matter regions until 48 weeks. Histology indicated demyelination, axonal degeneration and coagulative necrosis in all injured white matter. DTI can serve as a promising tool for assessment of radiation induced white matter injury and regional radiosensitivity of white matter tracts.

The performance of the progressive resolution optimizer (PRO) for RapidArc planning in targets with low-density media.

A new version of progressive resolution optimizer (PRO) with an option of air cavity correction has been implemented for RapidArc volumetric-modulated arc therapy (RA). The purpose of this study was to compare the performance of this new PRO with the use of air cavity correction option (PRO10_air) against the one without the use of the air cavity correction option (PRO10_no-air) for RapidArc planning in targets with low-density media of different sizes and complexities. The performance of PRO10_no-air and PRO10_air was initially compared using single-arc plans created for four different simple heterogeneous phantoms with virtual targets and organs at risk. Multiple-arc planning of 12 real patients having nasopharyngeal carcinomas (NPC) and ten patients having non-small cell lung cancer (NSCLC) were then performed using the above two options for further comparison. Dose calculations were performed using both the Acuros XB (AXB) algorithm with the dose to medium option and the analytical anisotropic algorithm (AAA). The effect of using intermediate dose option after the first optimization cycle in PRO10_air and PRO10_no-air was also investigated and compared. Plans were evaluated and compared using target dose coverage, critical organ sparing, conformity index, and dose homogeneity index. For NSCLC cases or cases for which large volumes of low-density media were present in or adjacent to the target volume, the use of the air cavity correction option in PRO10 was shown to be beneficial. For NPC cases or cases for which small volumes of both low- and high-density media existed in the target volume, the use of air cavity correction in PRO10 did not improve the plan quality. Based on the AXB dose calculation results, the use of PRO10_air could produce up to 18% less coverage to the bony structures of the planning target volumes for NPC cases. When the intermediate dose option in PRO10 was used, there was negligible difference observed in plan quality between optimizations with and without using the air cavity correction option.

Verification and dosimetric impact of Acuros XB algorithm on intensity modulated stereotactic radiotherapy for locally persistent nasopharyngeal carcinoma.

PURPOSE: The main aim of the current study was to assess the dosimetric impact on intensity modulated stereotactic radiotherapy (IMSRT) for locally persistent nasopharyngeal carcinoma (NPC) due to the recalculation from the Anisotropic Analytical Algorithm (AAA) to the recently released Acuros XB (AXB) algorithm. The dosimetric accuracy of using AXB in predicting air∕tissue interface doses from an open single small field in a simple geometric phantom and intensity modulated small fields in an anthropomorphic phantom was also investigated. METHODS: The central axis percentage depth doses (PDD) of a rectangular phantom containing an air cavity were calculated by both AAA and AXB from 6 MV beam with small field sizes (2 × 2 to 5 × 5 cm(2)). These data were compared to PDD measured by thin thermoluminescent dosimeters (TLDs) and Monte Carlo simulations. The doses predicted by AAA and AXB near air∕tissue interfaces from five different IMSRT plans were compared to the TLD measured doses in an anthropomorphic phantom. The PTV coverage, conformity and doses to organs at risk (OARs) calculated by AAA and AXB were compared for 12 patients, using identical beam setup, leaves movement and monitor units. RESULTS: Testing using the simple rectangular phantom demonstrated that AAA and AXB overestimated the PDD at the air∕tissue interfaces by up to 41% and 6%, respectively, from a 2 × 2 cm(2) field. The secondary build-up curves predicted by AXB caught up well with the measured data at around 2 mm beyond the air cavity. Testing using the anthropomorphic phantom showed that AAA overestimated the doses by up to 10%, while the measured doses matched those of the AXB to within 3%. Using AAA, the planning target coverage represented by 100% of the reference dose was estimated to be 4% higher than using AXB. The averaged minimum dose to the PTV predicted by AAA was about 4% higher and OARs doses 3% to 6% higher compared to AXB. CONCLUSIONS: AXB should be used whenever possible as the standard reference for IMSRT boost of NPC cases. The more accurate AXB indicating lower target coverage and lower minimum target dose compared to AAA should be noted.

A comprehensive dosimetric evaluation of using RapidArc volumetric-modulated arc therapy for the treatment of early-stage nasopharyngeal carcinoma.

The purpose of this study was to investigate the potential benefits of using triple-arc volumetric-intensity modulated arc radiotherapy (RapidArc (RA)) for the treatment of early-stage nasopharyngeal carcinoma (NPC). A comprehensive evaluation was performed including plan quality, integral doses, and peripheral doses. Twenty cases of stage I or II NPC were selected for this study. Nine-field sliding window IMRT, double-arc, and triple-arc RA treatment plans were compared with respect to target coverage, dose conformity, critical organ sparing, and integral doses. Measurement of peripheral doses was performed using thermoluminescent dosimeters in an anthropomorphic phantom. While similar conformity and target coverage were achieved by the three types of plans, triple-arc RA produced better sparing of parotid glands and spinal cord than double-arc RA or IMRT. Double-arc RA plans produced slightly inferior parotid sparing and dose homogeneity than the other two delivery methods. The monitor units (MU) required for triple-arc were about 50% less than those of IMRT plans, while there was no significant difference in the required MUs between triple-arc and double-arc RA plans. The peripheral dose in triple-arc RA was found to be 50% less compared to IMRT near abdominal and pelvic region. Triple-arc RA improves both the plan quality and treatment efficiency compared with IMRT for the treatment of early stage NPC. It has become the preferred choice of treatment delivery method for early stage NPC at our center.

Radiation dose from cone beam computed tomography for image-guided radiation therapy.

PURPOSE: To perform a comprehensive study on organ absorbed doses and effective doses from cone beam computed tomography (CBCT) for three different treatment sites. METHODS AND MATERIALS: An extensive set of dosimetric measurements were performed using a widely used CBCT system, the On-Board Imager (OBI). Measurements were performed using a female anthropomorphic phantom with thermoluminescent dosimeters (TLD). The effective doses to the body and the absorbed doses to 26 organs were reported using two different technical settings, namely, the standard mode and the low-dose mode. The measurements were repeated for three different scan sites: head and neck, chest, and pelvis. Comparisons of patient doses as well as image quality were performed among the standard mode CBCT, low-dose mode CBCT, and fan beam CT. RESULTS: The mean skin doses from standard mode CBCT to head and neck, chest and pelvis were 6.7, 6.4, and 5.4 cGy per scan, respectively. The effective doses to the body from standard mode CBCT for imaging of head and neck, chest, and pelvis were 10.3, 23.7, and 22.7 mSv per scan, respectively. Patient doses from low-dose mode CBCT were approximately one fifth of those from standard mode CBCT. CONCLUSIONS: Patient position verification by standard mode CBCT acquired by OBI on a daily basis could increase the secondary cancer risk by up to 2% to 4%. Therefore lower mAs settings for daily CBCT should be considered, especially when bony anatomy is the main interest.

Diffusion tensor magnetic resonance imaging finding of discrepant fractional anisotropy between the frontal and parietal lobes after whole-brain irradiation in childhood medulloblastoma survivors: reflection of regional white matter radiosensitivity?

PURPOSE: To test the hypothesis that fractional anisotropy (FA) is more severely reduced in white matter of the frontal lobe compared with the parietal lobe after receiving the same whole-brain irradiation dose in a cohort of childhood medulloblastoma survivors. METHODS AND MATERIALS: Twenty-two medulloblastoma survivors (15 male, mean [+/- SD] age = 12.1 +/- 4.6 years) and the same number of control subjects (15 male, aged 12.0 +/- 4.2 years) were recruited for diffusion tensor magnetic resonance imaging scans. Using an automated tissue classification method and the Talairach Daemon atlas, FA values of frontal and parietal lobes receiving the same radiation dose, and the ratio between them were quantified and denoted as FFA, PFA, and FA(f/p), respectively. The Mann-Whitney U test was used to test for significant differences of FFA, PFA, and FA(f/p) between medulloblastoma survivors and control subjects. RESULTS: Frontal lobe and parietal lobe white matter FA were found to be significantly less in medulloblastoma survivors compared with control subjects (frontal p = 0.001, parietal p = 0.026). Moreover, these differences were found to be discrepant, with the frontal lobe having a significantly larger difference in FA compared with the parietal lobe. The FA(f/p) of control and medulloblastoma survivors was 1.110 and 1.082, respectively (p = 0.029). CONCLUSION: Discrepant FA changes after the same irradiation dose suggest radiosensitivity of the frontal lobe white matter compared with the parietal lobe. Special efforts to address the potentially vulnerable frontal lobe after treatment with whole-brain radiation may be needed so as to balance disease control and treatment-related morbidity.

Predictive factors of tumor control and survival after radiosurgery for local failures of nasopharyngeal carcinoma.

BACKGROUND: Stereotactic radiosurgery has been employed as a salvage treatment of local failures of nasopharyngeal carcinoma (NPC). To identify patients that would benefit from radiosurgery, we reviewed our data with emphasis on factors that predicted treatment outcome. PATIENTS AND METHODS: A total of 48 patients with local failures of NPC were treated by stereotactic radiosurgery between March 1996 and February 2005. Radiosurgery was administered using a modified linear accelerator with single or multiple isocenters to deliver a median dose of 12.5 Gy to the target periphery. Median follow-up was 54 months. RESULTS: Five-year local failure-free probability after radiosurgery was 47.2% and 5-year overall survival rate was 46.9%. Neuroendocrine complications occurred in 27% of patients but there were no treatment-related deaths. Time interval from primary radiotherapy, retreatment T stage, prior local failures and tumor volume were significant predictive factors of local control and/or survival whereas age was of marginal significance in predicting survival. A radiosurgery prognostic scoring system was designed based on these predictive factors. Five-year local failure-free probabilities in patients with good, intermediate and poor prognostic scores were 100%, 42.5%, and 9.6%. The corresponding five-year overall survival rates were 100%, 51.1%, and 0%. CONCLUSION: Important factors that predicted tumor control and survival after radiosurgery were identified. Patients with good prognostic score should be treated by radiosurgery in view of the excellent results. Patients with intermediate prognostic score may also be treated by radiosurgery but those with poor prognostic score should receive other salvage treatments.

Preliminary results of radiation dose escalation for locally advanced nasopharyngeal carcinoma.

PURPOSE: To study the safety and efficacy of dose escalation in tumor for locally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From September 2000 to June 2004, 50 patients with T3-T4 NPC were treated with intensity-modulated radiotherapy (IMRT). Fourteen patients had Stage III and 36 patients had Stage IVA-IVB disease. The prescribed dose was 76 Gy to gross tumor volume (GTV), 70 Gy to planning target volume (PTV), and 72 Gy to enlarged neck nodes (GTVn). All doses were given in 35 fractions over 7 weeks. Thirty-four patients also had concurrent cisplatin and induction or adjuvant PF (cisplatin and 5-fluorouracil). RESULTS: The average mean dose achieved in GTV, GTVn, and PTV were 79.5 Gy, 75.3 Gy, and 74.6 Gy, respectively. The median follow-up was 25 months, with 4 recurrences: 2 locoregional and 2 distant failures. All patients with recurrence had IMRT alone without chemotherapy. The 2-year locoregional control rate, distant metastases-free and disease-free survivals were 95.7%, 94.2%, and 93.1%, respectively. One treatment-related death caused by adjuvant chemotherapy occurred. The 2-year overall survival was 92.1%. CONCLUSIONS: Dose escalation to 76 Gy in tumor is feasible with T3-T4 NPC and can be combined with chemotherapy. Initial results showed good local control and survival.

Evaluation and optimization of the parameters used in multiple-atlas-based segmentation of prostate cancers in radiation therapy.

OBJECTIVE: To evaluate and optimize the parameters used in multiple-atlas-based segmentation of prostate cancers in radiation therapy. METHODS: A retrospective study was conducted, and the accuracy of the multiple-atlas-based segmentation was tested on 30 patients. The effect of library size (LS), number of atlases used for contour averaging and the contour averaging strategy were also studied. The autogenerated contours were compared with the manually drawn contours. Dice similarity coefficient (DSC) and Hausdorff distance were used to evaluate the segmentation agreement. RESULTS: Mixed results were found between simultaneous truth and performance level estimation (STAPLE) and majority vote (MV) strategies. Multiple-atlas approaches were relatively insensitive to LS. A LS of ten was adequate, and further increase in the LS only showed insignificant gain. Multiple atlas performed better than single atlas for most of the time. Using more atlases did not guarantee better performance, with five atlases performing better than ten atlases. With our recommended setting, the median DSC for the bladder, rectum, prostate, seminal vesicle and femurs was 0.90, 0.77, 0.84, 0.56 and 0.95, respectively. CONCLUSION: Our study shows that multiple-atlas-based strategies have better accuracy than single-atlas approach. STAPLE is preferred, and a LS of ten is adequate for prostate cases. Using five atlases for contour averaging is recommended. The contouring accuracy of seminal vesicle still needs improvement, and manual editing is still required for the other structures. ADVANCES IN KNOWLEDGE: This article provides a better understanding of the influence of the parameters used in multiple-atlas-based segmentation of prostate cancers.

Re-irradiation of nasopharyngeal carcinoma with intensity-modulated radiotherapy.

BACKGROUND AND PURPOSE: To evaluate the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: Between October 2001 and May 2004, 31 patients with locally recurrent NPC received re-irradiation using IMRT. The rT classification distribution was 3 for rT1, 5 for rT2, 9 for rT3, and 14 for r T4. Median time from first course of radiotherapy to re-irradiation was 51 months. IMRT was performed using step-and-shoot method with nine 4-6 MV photon fields and median prescribed dose was 54 Gy (range: 50-60 Gy). Additional treatments included cisplatin-based induction chemotherapy in 68% and radiosurgery boost with a single dose which ranged from 8.5 to 12.5 Gy in 32%. Median follow-up time was 11 months. RESULTS: After re irradiation, 58% of patients had complete regression of primary tumor. One-year loco-regional progression-free, distant metastasis-free and overall survival rates were 56, 90, and 63%, respectively. Significantly better 1-year local progression-free rate was observed in rT1-3 than r T4 tumor (100 vs. 35%). Grade 3 late toxicities, mostly ototoxicity/cranial neuropathy, occurred in six patients (19%). One-year actuarial rates of late toxicities were 70% for all grades and 25% for Grade 3. CONCLUSION: Our preliminary results showed that good control of rT1-3 NPC can be achieved using IMRT with a dose between 50 and 60 Gy, whereas the outcome for r T4 tumor remained poor. Late toxicities were common but incidence of severe toxicities was relatively low.

Linear accelerator-based stereotactic radiosurgery for limited, locally persistent, and recurrent nasopharyngeal carcinoma: efficacy and complications.

PURPOSE: To evaluate the efficacy and complication of linear accelerator-based stereotactic radiosurgery (SRS) when used as salvage treatment for early-stage persistent and recurrent nasopharyngeal carcinoma (NPC) after primary radiotherapy (RT). MATERIALS AND METHODS: Between March 1998 and June 2001, 18 patients (15 men and 3 women; median age 46 years, range 32-84) with locally persistent or recurrent NPC confined to the nasopharynx (rT1) or with limited extension to the nasal fossa or parapharyngeal space (rT2) were treated by SRS. Thirteen patients had rT1 disease and 5 had rT2 disease. Most patients had disease not amenable to surgery or brachytherapy. All patients had undergone previous radical RT. Persistent disease was defined as tumor relapse within 4 months of completion of primary RT, and recurrence as tumor relapse beyond 4 months. Seven patients were treated for persistent disease, eight for a first recurrence, and three for a second recurrence. SRS was performed using multiple noncoplanar arcs of photons delivered to the target volume, which was defined by axial CT at a 3 mm thickness, supplemented by MRI in selected patients (67%). The median target volume was 5.3 cm(3) (range 2.2-16.9). The median SRS dose was 12.5 Gy (range 11-14) delivered to the 80% isodose line. All patients underwent serial nasopharyngoscopy and imaging after SRS. The median follow-up was 26 months (range 11-48). RESULTS: After SRS, 16 (89%) of 18 patients had complete regression of tumor as assessed by nasopharyngoscopy and biopsy. Four patients with an initial complete response to SRS subsequently developed local relapse again, with one recurrence developing outside the target volume 8 months after SRS and three within the target volume at 6-26 months after SRS. Two patients with local disease controlled by SRS developed relapse in other sites (neck node and liver metastases). The actuarial 2-year local control rate after SRS was 72%. Patients treated for persistent disease had a better local control rate (100%; 7 of 7) than those treated for recurrent disease (46%; 5 of 11). Patients with rT1 disease also had a better outcome after SRS compared with those with rT2 disease, with a control rate of 77% (10 of 13) for rT1 disease and 40% (2 of 5) for rT2 disease. Treatments were well tolerated, with no acute side effects. One patient had radiologic evidence of temporal lobe necrosis, although the right temporal lobe had already received a high dose during prior RT. That patient also developed additional local recurrence and liver metastases and died. The actuarial 2-year survival rate was 86%. CONCLUSIONS: Our preliminary results indicate that SRS is an effective treatment modality for persistent and recurrent early-stage NPC, with early control rates comparable to other salvage treatments such as brachytherapy and nasopharyngectomy. A modest SRS dose at 12.5 Gy also appears to be effective and is associated with minimal morbidities. More clinical experience and longer follow-up are needed to validate our results and to address fully the role of SRS in salvaging local failures of NPC.

Tumor volume is not an independent prognostic factor in early-stage nasopharyngeal carcinoma treated by radiotherapy alone.

PURPOSE: To determine whether the tumor volume can predict the treatment outcome in early-stage nasopharyngeal carcinoma (NPC) treated by radiotherapy alone. METHODS AND MATERIALS: The pretreatment CT scans of 116 patients with American Joint Committee on Cancer Stage I-II NPC treated by radiotherapy alone were retrospectively reviewed. The clinician outlined the tumor extent. The primary tumor volume (PTV) and nodal volume (NV) were then calculated by a summation-of-areas technique. The PTV and NV were correlated with locoregional control, distant failure, and survival. The median follow-up time was 105 months. RESULTS: Patients with Stage I disease had a 5-year locoregional control rate of 95% and a disease-specific survival (DSS) rate of 97%; for Stage II disease, the corresponding rates were 81% and 79%. The PTV ranged from 1.3 to 75.5 cm3 (median, 12.6 cm3), with substantial overlap between T1 and T2 disease. The NV ranged from 0 to 35.4 cm(3). Patients with a PTV >15 cm3 had significantly worse local control (5-year control rate, 82% vs. 93%; p = 0.033), but no statistically significant difference was noted in survival (5-year DSS rate, 83% vs. 89%; p = 0.30). The difference in local control was mainly seen in those with T2 disease. Patients with NV >4 cm3 had a greater distant failure rate (5-year distant metastasis-free rate, 72% vs. 90%; p = 0.011) and worse survival (5-year DSS rate, 76% vs. 94%; p = 0.0038). Nodal control was excellent with no difference between a NV of < or =4 cm3 and a NV of >4 cm3 (5-year control rate, 97% vs. 100%). The survival rate was worst in patients with a PTV >15 cm3 and a NV >4 cm3 (5-year DSS rate, 68%) and best in those with a PTV of < or =15 cm3 and a NV of < or =4 cm3 (5-year DSS rate, 92%). Multivariate analysis, however, showed that only parapharyngeal extension (T2b) and N1 stage were independent factors that predicted locoregional control and survival, and N1 stage was the only factor that predicted distant failure. CONCLUSION: The pretreatment tumor volume has a limited prognostic value in early-stage NPC compared with the usual T and N classification, with Stage T2b and N1 as independent factors that predicted treatment outcome. Within T2 disease, the estimation of tumor volume may identify a subgroup of patients with a greater risk of local failure that warrants more aggressive treatment.

The use of biologically related model (Eclipse) for the intensity-modulated radiation therapy planning of nasopharyngeal carcinomas.

PURPOSE: Intensity-modulated radiation therapy (IMRT) is the most common treatment technique for nasopharyngeal carcinoma (NPC). Physical quantities such as dose/dose-volume parameters are used conventionally for IMRT optimization. The use of biological related models has been proposed and can be a new trend. This work was to assess the performance of the biologically based IMRT optimization model installed in a popular commercial treatment planning system (Eclipse) as compared to its dose/dose volume optimization model when employed in the clinical environment for NPC cases. METHODS: Ten patients of early stage NPC and ten of advanced stage NPC were selected for this study. IMRT plans optimized using biological related approach (BBTP) were compared to their corresponding plans optimized using the dose/dose volume based approach (DVTP). Plan evaluation was performed using both biological indices and physical dose indices such as tumor control probability (TCP), normal tissue complication probability (NTCP), target coverage, conformity, dose homogeneity and doses to organs at risk. The comparison results of the more complex advanced stage cases were reported separately from those of the simpler early stage cases. RESULTS: The target coverage and conformity were comparable between the two approaches, with BBTP plans producing more hot spots. For the primary targets, BBTP plans produced comparable TCP for the early stage cases and higher TCP for the advanced stage cases. BBTP plans reduced the volume of parotid glands receiving doses of above 40 Gy compared to DVTP plans. The NTCP of parotid glands produced by BBTP were 8.0 ± 5.8 and 7.9 ± 8.7 for early and advanced stage cases, respectively, while those of DVTP were 21.3 ± 8.3 and 24.4 ± 12.8, respectively. There were no significant differences in the NTCP values between the two approaches for the serial organs. CONCLUSIONS: Our results showed that the BBTP approach could be a potential alternative approach to the DVTP approach for NPC.

Dosimetric impact of using the Acuros XB algorithm for intensity modulated radiation therapy and RapidArc planning in nasopharyngeal carcinomas.

PURPOSE: To assess the dosimetric implications for the intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy with RapidArc (RA) of nasopharyngeal carcinomas (NPC) due to the use of the Acuros XB (AXB) algorithm versus the anisotropic analytical algorithm (AAA). METHODS AND MATERIALS: Nine-field sliding window IMRT and triple-arc RA plans produced for 12 patients with NPC using AAA were recalculated using AXB. The dose distributions to multiple planning target volumes (PTVs) with different prescribed doses and critical organs were compared. The PTVs were separated into components in bone, air, and tissue. The change of doses by AXB due to air and bone, and the variation of the amount of dose changes with number of fields was also studied using simple geometric phantoms. RESULTS: Using AXB instead of AAA, the averaged mean dose to PTV70 (70 Gy was prescribed to PTV70) was found to be 0.9% and 1.2% lower for IMRT and RA, respectively. It was approximately 1% lower in tissue, 2% lower in bone, and 1% higher in air. The averaged minimum dose to PTV70 in bone was approximately 4% lower for both IMRT and RA, whereas it was approximately 1.5% lower for PTV70 in tissue. The decrease in target doses estimated by AXB was mostly contributed from the presence of bone, less from tissue, and none from air. A similar trend was observed for PTV60 (60 Gy was prescribed to PTV60). The doses to most serial organs were found to be 1% to 3% lower and to other organs 4% to 10% lower for both techniques. CONCLUSIONS: The use of the AXB algorithm is highly recommended for IMRT and RapidArc planning for NPC cases.

The effect of the target-organ geometric complexity on the choice of delivery between RapidArc and sliding-window IMRT for nasopharyngeal carcinoma.

We attempted to assess the effect of target-organ geometric complexity on the plan quality of sliding-window intensity-modulated radiotherapy (IMRT), double-arc (RA2), and triple-arc (RA3) RapidArc volumetric-modulated arc radiotherapy for nasopharyngeal carcinoma (NPC). Plans for 9-field sliding-window IMRT, RA2, and RA3 were optimized for 36 patients with NPC ranging from T1 to T4 tumors. Initially the patients were divided into 2 groups, with group A representing the most simple early stage (T1 and T2) cases, whereas group B represented the more complex advanced cases (T3 and T4). Evaluation was performed based on target conformity, target dose homogeneity, organ-sparing capability, and delivery efficiency. Based on the plan quality results, a subgroup of advanced cases, group B2, representing the most demanding task was distinguished and reported separately from the rest of the group B cases, B1. Detailed analysis was performed on the anatomic features for each group of cases, so that planners can easily identify the differences between B1 and B2. For the group A cases, RA3 plans were superior to the IMRT plans in terms of organ sparing, whereas target conformity and dose homogeneity were similar. For the group B1 cases, the RA3 plans produced almost equivalent plan quality as the IMRT plans. For the group B2 cases, for most of which large target volumes were adjacent to (5mm or less) and wrapping around the brain stem, RA2 and RA3 were inferior to the IMRT regarding both target dose homogeneity and conformity. RA2 plans were slightly inferior to IMRT and RA3 plans for most cases. The plan comparison results depend on the target to brain stem distances and the target sizes. The plan quality results together with the anatomic information may allow the evaluation of the 3 treatment options before actual planning.

A review on the use of grid-based Boltzmann equation solvers for dose calculation in external photon beam treatment planning.

Deterministic linear Boltzmann transport equation (D-LBTE) solvers have recently been developed, and one of the latest available software codes, Acuros XB, has been implemented in a commercial treatment planning system for radiotherapy photon beam dose calculation. One of the major limitations of most commercially available model-based algorithms for photon dose calculation is the ability to account for the effect of electron transport. This induces some errors in patient dose calculations, especially near heterogeneous interfaces between low and high density media such as tissue/lung interfaces. D-LBTE solvers have a high potential of producing accurate dose distributions in and near heterogeneous media in the human body. Extensive previous investigations have proved that D-LBTE solvers were able to produce comparable dose calculation accuracy as Monte Carlo methods with a reasonable speed good enough for clinical use. The current paper reviews the dosimetric evaluations of D-LBTE solvers for external beam photon radiotherapy. This content summarizes and discusses dosimetric validations for D-LBTE solvers in both homogeneous and heterogeneous media under different circumstances and also the clinical impact on various diseases due to the conversion of dose calculation from a conventional convolution/superposition algorithm to a recently released D-LBTE solver.

Experimental verification of the Acuros XB and AAA dose calculation adjacent to heterogeneous media for IMRT and RapidArc of nasopharygeal carcinoma.

PURPOSE: To compare the doses calculated by the Acuros XB (AXB) algorithm and analytical anisotropic algorithm (AAA) with experimentally measured data adjacent to and within heterogeneous medium using intensity modulated radiation therapy (IMRT) and RapidArc(®) (RA) volumetric arc therapy plans for nasopharygeal carcinoma (NPC). METHODS: Two-dimensional dose distribution immediately adjacent to both air and bone inserts of a rectangular tissue equivalent phantom irradiated using IMRT and RA plans for NPC cases were measured with GafChromic(®) EBT3 films. Doses near and within the nasopharygeal (NP) region of an anthropomorphic phantom containing heterogeneous medium were also measured with thermoluminescent dosimeters (TLD) and EBT3 films. The measured data were then compared with the data calculated by AAA and AXB. For AXB, dose calculations were performed using both dose-to-medium (AXB_Dm) and dose-to-water (AXB_Dw) options. Furthermore, target dose differences between AAA and AXB were analyzed for the corresponding real patients. The comparison of real patient plans was performed by stratifying the targets into components of different densities, including tissue, bone, and air. RESULTS: For the verification of planar dose distribution adjacent to air and bone using the rectangular phantom, the percentages of pixels that passed the gamma analysis with the ± 3%/3mm criteria were 98.7%, 99.5%, and 97.7% on the axial plane for AAA, AXB_Dm, and AXB_Dw, respectively, averaged over all IMRT and RA plans, while they were 97.6%, 98.2%, and 97.7%, respectively, on the coronal plane. For the verification of planar dose distribution within the NP region of the anthropomorphic phantom, the percentages of pixels that passed the gamma analysis with the ± 3%/3mm criteria were 95.1%, 91.3%, and 99.0% for AAA, AXB_Dm, and AXB_Dw, respectively, averaged over all IMRT and RA plans. Within the NP region where air and bone were present, the film measurements represented the dose close to unit density water in a heterogeneous medium, produced the best agreement with the AXB_Dw. For the verification of point doses within the target using TLD in the anthropomorphic phantom, the absolute percentage deviations between the calculated and measured data when averaged over all IMRT and RA plans were 1.8%, 1.7%, and 1.8% for AAA, AXB_Dm and AXB_Dw, respectively. From all the verification results, no significant difference was found between the IMRT and RA plans. The target dose analysis of the real patient plans showed that the discrepancies in mean doses to the PTV component in tissue among the three dose calculation options were within 2%, but up to about 4% in the bone content, with AXB_Dm giving the lowest values and AXB_Dw giving the highest values. CONCLUSIONS: In general, the verification measurements demonstrated that both algorithms produced acceptable accuracy when compared to the measured data. GafChromic(®) film results indicated that AXB produced slightly better accuracy compared to AAA for dose calculation adjacent to and within the heterogeneous media. Users should be aware of the differences in calculated target doses between options AXB_Dm and AXB_Dw, especially in bone, for IMRT and RA in NPC cases.

A new approach to computing normal tissue complication probability of an intensity-modulated radiotherapy treatment with stereotactic radiotherapy boost of nasopharyngeal carcinoma: a case study.

We attempted to develop a method to compute the normal tissue complication probability (NTCP) of various critical organs from combined intensity-modulated radiotherapy (IMRT) and stereotactic radiotherapy (SRT) boost treatment of nasopharyngeal carcinoma (NPC), with the aid of a nonlinear image registration method. The SRT's planning computed tomography (CT) of a NPC patient treated with IMRT was warped to the IMRT's planning CT using a nonlinear image registration. Because CT and dose were inherently in-register, the entire dose distribution could be deformed using the same deformation field derived from the two CT sets. Using the biologically effective dose concept and the linear-quadratic model, physical doses of IMRT and SRT were converted to a 2 Gy-per-fraction equivalent dose to facilitate dose summation. The variation of organs' maximum doses of the combined treatments between traditional maximum dose sum and the proposed method was 1.5 Gy ± 1.7 Gy. After the correction of the effect of fractionation and dose heterogeneity within each organ, NTCP of each organ of interest was computed for the combined treatments. Based on the results of this case study, it is believed that dose registration could be a method for the NTCP computation of various critical organs when different fractionation schemes of radiation therapy treatment are instituted.

Peripheral doses from noncoplanar IMRT for pediatric radiation therapy.

The use of noncoplanar intensity-modulated radiation therapy (IMRT) might result in better sparing of some critical organs because of a higher degree of freedom in beam angle optimization. However, this can lead to a potential increase in peripheral dose compared with coplanar IMRT. The peripheral dose from noncoplanar IMRT has not been previously quantified. This study examines the peripheral dose from noncoplanar IMRT compared with coplanar IMRT for pediatric radiation therapy. Five cases with different pediatric malignancies in head and neck were planned with both coplanar and noncoplanar IMRT techniques. The plans were performed such that the tumor coverage, conformality, and dose uniformity were comparable for both techniques. To measure the peripheral doses of the 2 techniques, thermoluminescent dosimeters (TLD) were placed in 10 different organs of a 5-year-old pediatric anthropomorphic phantom. With the use of noncoplanar beams, the peripheral doses to the spinal cord, bone marrow, lung, and breast were found to be 1.8-2.5 times of those using the coplanar technique. This is mainly because of the additional internal scatter dose from the noncoplanar beams. Although the use of noncoplanar technique can result in better sparing of certain organs such as the optic nerves, lens, or inner ears depending on how the beam angles were optimized on each patient, oncologists should be alert of the possibility of significantly increasing the peripheral doses to certain radiation-sensitive organs such as bone marrow and breast. This might increase the secondary cancer risk to patients at young age.

Longitudinal diffusion tensor magnetic resonance imaging study of radiation-induced white matter damage in a rat model.

Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (lambda(//)), and radial diffusivity (lambda( perpendicular)) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in lambda(//) from 4 to 40 weeks postradiation, and an increase in lambda( perpendicular) with return to baseline in lambda(//) at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in lambda(//) correlated with reactive astrogliosis (P < 0.01) and lambda( perpendicular) correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in lambda(//) and lambda( perpendicular). DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.