Predicting vertebral compression fracture prior to spinal SBRT using radiomics from planning CT.

PURPOSE: The purpose of the study was to develop a predictive model for vertebral compression fracture (VCF) prior to spinal stereotactic body radiation therapy (SBRT) using radiomics features extracted from pre-treatment planning CT images. METHODS: A retrospective analysis was conducted on 85 patients (114 spinal lesions) who underwent spinal SBRT. Radiomics features were extracted from pre-treatment planning CT images and used to develop a predictive model using a classification algorithm selected from nine different machine learning algorithms. Four different models were trained, including clinical features only, clinical and radiomics features, radiomics and dosimetric features, and all features. Model performance was evaluated using accuracy, precision, recall, F1-score, and area under the curve (AUC). RESULTS: The model that used all features (radiomics, clinical, and dosimetric) showed the highest performance with an AUC of 0.871. The radiomics and dosimetric features model had the superior performance in terms of accuracy, precision, recall, and F1-score. CONCLUSION: The developed predictive model based on radiomics features extracted from pre-treatment planning CT images can accurately predict the likelihood of VCF prior to spinal SBRT. This model has significant implications for treatment planning and preventive measures for patients undergoing spinal SBRT. Future research can focus on improving model performance by incorporating new data and external validation using independent data sets.

Locoregional Recurrence Prediction Using a Deep Neural Network of Radiological and Radiotherapy Images.

Radiation therapy (RT) is an important and potentially curative modality for head and neck squamous cell carcinoma (HNSCC). Locoregional recurrence (LR) of HNSCC after RT is ranging from 15% to 50% depending on the primary site and stage. In addition, the 5-year survival rate of patients with LR is low. To classify high-risk patients who might develop LR, a deep learning model for predicting LR needs to be established. In this work, 157 patients with HNSCC who underwent RT were analyzed. Based on the National Cancer Institute's multi-institutional TCIA data set containing FDG-PET/CT/dose, a 3D deep learning model was proposed to predict LR without time-consuming segmentation or feature extraction. Our model achieved an averaged area under the curve (AUC) of 0.856. Adding clinical factors into the model improved the AUC to an average of 0.892 with the highest AUC of up to 0.974. The 3D deep learning model could perform individualized risk quantification of LR in patients with HNSCC without time-consuming tumor segmentation.

Medical X-band linear accelerator for high-precision radiotherapy.

PURPOSE: Recently, high-precision radiotherapy systems have been developed by integrating computerized tomography or magnetic resonance imaging to enhance the precision of radiotherapy. For integration with additional imaging systems in a limited space, miniaturization and weight reduction of the linear accelerator (linac) system have become important. The aim of this work is to develop a compact medical linac based on 9.3 GHz X-band RF technology instead of the S-band RF technology typically used in the radiotherapy field. METHODS: The accelerating tube was designed by 3D finite-difference time-domain and particle-in-cell simulations because the frequency variation resulting from the structural parameters and processing errors is relatively sensitive to the operating performance of the X-band linac. Through the 3D simulation of the electric field distribution and beam dynamics process, we designed an accelerating tube to efficiently accelerate the electron beam and used a magnetron as the RF source to miniaturize the entire linac. In addition, a side-coupled structure was adopted to design a compact linac to reduce the RF power loss. To verify the performance of the linac, we developed a beam diagnostic system to analyze the electron beam characteristics and a quality assurance (QA) experimental environment including 3D lateral water phantoms to analyze the primary performance parameters (energy, dose rate, flatness, symmetry, and penumbra) The QA process was based on the standard protocols AAPM TG-51, 106, 142 and IAEA TRS-398. RESULTS: The X-band linac has high shunt impedance and electric field strength. Therefore, even though the length of the accelerating tube is 37 cm, the linac could accelerate an electron beam to more than 6 MeV and produce a beam current of more than 90 mA. The transmission ratio is measured to be approximately 30% ~ 40% when the electron gun operates in the constant emission region. The percent depth dose ratio at the measured depths of 10 and 20 cm was approximately 0.572, so we verified that the photon beam energy was matched to approximately 6 MV. The maximum dose rate was measured as 820 cGy/min when the source-to-skin distance was 80 cm. The symmetry was smaller than the QA standard and the flatness had a higher than standard value due to the flattening filter-free beam characteristics. In the case of the penumbra, it was not sufficiently steep compared to commercial equipment, but it could be compensated by improving additional devices such as multileaf collimator and jaw. CONCLUSIONS: A 9.3 GHz X-band medical linac was developed for high-precision radiotherapy. Since a more precise design and machining process are required for X-band RF technology, this linac was developed by performing a 3D simulation and ultraprecision machining. The X-band linac has a short length and a compact volume, but it can generate a validated therapeutic beam. Therefore, it has more flexibility to be coupled with imaging systems such as CT or MRI and can reduce the bore size of the gantry. In addition, the weight reduction can improve the mechanical stiffness of the unit and reduce the mechanical load.

Development of a compact X-band linear accelerator system mounted on an O-arm rotating gantry for radiation therapy.

A compact X-band linear accelerator (LINAC) system equipped with a small and lightweight magnetron was constructed to develop a high-precision image-guided radiotherapy system. The developed LINAC system was installed in an O-ring gantry where cone-beam computed tomography (CBCT) was embedded. When the O-arm gantry is rotated, an x-ray beam is stably generated, which resulted from the stable transmission of radio frequency power into the X-band LINAC system. Quality assurance (QA) tests, including mechanical and dosimetry checks, were carried out to ensure safety and operation performance according to the American Association of Physicists in Medicine's TG-51, 142, an international standard protocol established by accredited institutions. In addition, delivery QA of the radiotherapy planning system was conducted to verify intensity-modulated radiotherapy techniques. Therefore, it was demonstrated that the developed X-band LINAC system mounted on the O-arm gantry proved to be valid and reliable for potential use in CBCT image-guided radiation therapy.

Assessment of planning reproducibility in three-dimensional field-in-field radiotherapy technique for breast cancer: impact of surgery-simulation interval.

The three-dimensional field-in-field (3-D FIF) technique for radiotherapy is an advanced, state-of-the-art method that uses multileaf collimators to generate a homogeneous and conformal dose distribution via segmental subfields. The purpose of this study is to evaluate the dosimetric reproducibility of 3-D FIF plans using the original simulation computed tomography (iCT) scans and re-simulation CT (rCT) scans for whole breast irradiation (WBI) schedule. This study enrolled a total of 34 patients. The study population underwent iCT scans for standard WBI and took rCT scans after 45 Gy of WBI for cone down boost plans. The dosimetric parameters (V105%, V103%, V100%, V98%, V95%, V90%, V50%), plan quality indices (conformity index, homogeneity index) and clinical parameters (isocenter-breast axis, isocenter-lung axis, soft tissue volumes within radiation field, lung volumes within radiation field) were assessed. The median time interval from surgery to iCT was 33 days and from iCT to rCT was 35 days. All dosimetric parameters exhibited statistically significant differences between iCT and rCT among cohorts with a surgery-iCT interval of < 60 days. Homogeneity index showed a statistically significant increase from iCT to rCT among all cohorts. Soft tissue volumes (p = 0.001) and isocenter-breast axis (p = 0.032) exhibited statistically significant differences among cohorts with surgery-iCT interval < 60 days. Regarding the reproducibility of the 3-D FIF WBI plans, significant changes were observed in dosimetric and clinical factors, particularly in study cohorts with a surgery-simulation interval < 60 days. The main contributing factor of these transitions seemed to be the changes in volume of the soft tissue within the WBI field. Further confirmative studies are necessary to determine the most suitable timing and technique for WBI.

Upfront radiosurgery plus targeted agents followed by active brain control using radiosurgery delays neurological death in non-small cell lung cancer with brain metastasis.

The role of radiosurgery has become further accentuated in the era of targeted agents (TA). Thus, the neurologic outcome of radiosurgery in brain metastasis (BM) of non-small cell lung cancer (NSCLC) was reviewed. We analyzed 135 patients with BM of NSCLC who were administered Cyberknife radiosurgery (CKRS) as either initial or salvage therapy. We evaluated local failure (LF), intracranial failure (IF), and neurological death (ND) due to BM. Primary outcome was neurological death-free survival (NDFS). Median follow-up was 16.2 months. Median CKRS dose of 22 Gy was administered to median 2 targets per patient. Among 99 deaths, 14 (14%) were ND. Upfront treatment for BM included CKRS alone in 85 patients (63%), CKRS + TA in 26 patients (19%), and WBRT in 24 patients (18%). No patients or tumor related factors were associated with ND. However, the type of upfront treatment for BM was significantly associated with ND [HR 0.07 (95% CI 0.01-0.57) for CKRS + TA, HR 0.56 (95% CI 0.19-1.68) for CKRS alone] compared with the WBRT group (P = 0.01). The 2-year NDFS rates for the CKRS + TA, CRKS alone, and WBRT groups were 94%, 87%, and 78%, respectively (P = 0.03). Upfront CKRS showed significantly higher 2-year LF-free survival rate (P < 0.01). IF rate was insignificantly lower in the WBRT group compared with CKRS group (P = 0.38). Upfront CKRS + TA was associated with the best neurological outcome with high NDFS. Active brain control by early delivery of radiosurgery could achieve better neurological outcome in NSCLC with BM.

Verification of lithium formate monohydrate in 3D-printed container for electron paramagnetic resonance dosimetry in radiotherapy.

The nondestructive dosimetry achieved with electron paramagnetic resonance (EPR) dosimetry facilitates repetitive recording by the same dosimeter to increase the reliability of data. In precedent studies, solid paraffin was needed as a binder material to make the lithium formate monohydrate (LFM) EPR dosimeter stable and nonfragile; however, its use complicates dosimetry. This study proposes a newly designed pure LFM EPR dosimeter created by inserting LFM into a 3D-printed container. Dosimetric characteristics of the LFM EPR dosimeter and container, such as reproducibility, linearity, energy dependence, and angular dependence, were evaluated and verified through a radiation therapy planning system (RTPS). The LFM EPR dosimeters were irradiated using a clinical linear accelerator. The EPR spectra of the dosimeters were acquired using a Bruker EMX EPR spectrometer. Through this study, it was confirmed that there is no tendency in the EPR response of the container based on irradiation dose or radiation energy. The results show that the LFM EPR dosimeters have a highly sensitive dose response with good linearity. The energy dependence across each photon and electron energy range seems to be negligible. Based on these results, LFM powder in a 3D-printed container is a suitable option for dosimetry of radiotherapy. Furthermore, the LFM EPR dosimeter has considerable potential for in vivo dosimetry and small-field dosimetry via additional experiments, owing to its small effective volume and highly sensitive dose response compared with a conventional dosimeter.

4D digital tomosynthesis image reconstruction using brute force-based adaptive total variation (BF-ATV) in a prototype LINAC system.

Respiratory-correlated cone-beam CT (CBCT) not only inhibits rapid scanning due to the slow speed of the LINAC head gantry rotation, but its implementation for routine patient imaging is impractical because of the high radiation dose delivered during the process. Digital tomosynthesis (DTS) is a potentially faster technique that delivers a much lower radiation dose by reducing the number of projections in a limited angular range. Unfortunately, 4D-DTS introduces strong aliasing artifacts in the reconstructed images due to the sparsely sampled projections in each respiratory phase bin. The authors hereby suggest a novel low-dose 4D-DTS image reconstruction method that achieves a compromise between the occurrence of aliasing artifacts and image smoothing using a brute force-based adaptive weighting parameter searching technique. We used a prototype LINAC system mounted with a flat-panel detector to acquire tomosynthesis projections of respiratory motion in a phantom in the anterior-posterior (AP) and lateral views. Three different 4D-DTS image reconstruction schemes that included conventional filtered back-projection (FBP), adaptive steepest descent projection onto convex sets (ASD-POCS), and the proposed brute force-based adaptive total variation (BF-ATV) were implemented in four different respiratory phase bins for both AP and lateral views. All reconstructions were accelerated using a single GPU card to reduce the computation time. To study the performance of the algorithm under various sparse conditions, we operated the prototype system in three different gantry sweep modes. The results indicate that the proposed BF-ATV method yields the largest structural similarities in the differenced image between the ground-truth dataset acquired using the slow gantry sweep mode and the sparse dataset from both moderate and fast sweep modes. In addition, the proposed method maintained the object sharpness with less streaking lines and small loss of sharpness compared to the conventional FBP and ASD-POCS methods. In conclusion, the proposed low-dose 4D-DTS reconstruction scheme may provide better performance due in part to its rapid scanning. Therefore, it is potentially applicable to practical 4D imaging for radiotherapy.

Dosimetric comparison between modulated arc therapy and static intensity modulated radiotherapy in thoracic esophageal cancer: a single institutional experience.

PURPOSE: The objective of this study was to compare dosimetric characteristics of three-dimensional conformal radiotherapy (3D-CRT) and two types of intensity-modulated radiotherapy (IMRT) which are step-and-shoot intensity modulated radiotherapy (s-IMRT) and modulated arc therapy (mARC) for thoracic esophageal cancer and analyze whether IMRT could reduce organ-at-risk (OAR) dose. MATERIALS AND METHODS: We performed 3D-CRT, s-IMRT, and mARC planning for ten patients with thoracic esophageal cancer. The dose-volume histogram for each plan was extracted and the mean dose and clinically significant parameters were analyzed. RESULTS: Analysis of target coverage showed that the conformity index (CI) and conformation number (CN) in mARC were superior to the other two plans (CI, p = 0.050; CN, p = 0.042). For the comparison of OAR, lung V5 was lowest in s-IMRT, followed by 3D-CRT, and mARC (p = 0.033). s-IMRT and mARC had lower values than 3D-CRT for heart V30 (p = 0.039), V40 (p = 0.040), and V50 (p = 0.032). CONCLUSION: Effective conservation of the lung and heart in thoracic esophageal cancer could be expected when using s-IMRT. The mARC was lower in lung V10, V20, and V30 than in 3D-CRT, but could not be proven superior in lung V5. In conclusion, low-dose exposure to the lung and heart were expected to be lower in s-IMRT, reducing complications such as radiation pneumonitis or heart-related toxicities.

Image similarity evaluation of the bulk-density-assigned synthetic CT derived from MRI of intracranial regions for radiation treatment.

OBJECTIVE: Various methods for radiation-dose calculation have been investigated over previous decades, focusing on the use of magnetic resonance imaging (MRI) only. The bulk-density-assignment method based on manual segmentation has exhibited promising results compared to dose-calculation with computed tomography (CT). However, this method cannot be easily implemented in clinical practice due to its time-consuming nature. Therefore, we investigated an automatic anatomy segmentation method with the intention of providing the proper methodology to evaluate synthetic CT images for a radiation-dose calculation based on MR images. METHODS: CT images of 20 brain cancer patients were selected, and their MR images including T1-weighted, T2-weighted, and PETRA were retrospectively collected. Eight anatomies of the patients, such as the body, air, eyeball, lens, cavity, ventricle, brainstem, and bone, were segmented for bulk-density-assigned CT image (BCT) generation. In addition, water-equivalent CT images (WCT) with only two anatomies-body and air-were generated for a comparison with BCT. Histogram comparison and gamma analysis were performed by comparison with the original CT images, after the evaluation of automatic segmentation performance with the dice similarity coefficient (DSC), false negative dice (FND) coefficient, and false positive dice (FPD) coefficient. RESULTS: The highest DSC value was 99.34 for air segmentation, and the lowest DSC value was 73.50 for bone segmentation. For lens segmentation, relatively high FND and FPD values were measured. The cavity and bone were measured as over-segmented anatomies having higher FPD values than FND. The measured histogram comparison results of BCT were better than those of WCT in all cases. In gamma analysis, the averaged improvement of BCT compared to WCT was measured. All the measured results of BCT were better than those of WCT. Therefore, the results of this study show that the introduced methods, such as histogram comparison and gamma analysis, are valid for the evaluation of the synthetic CT generation from MR images. CONCLUSIONS: The image similarity results showed that BCT has superior results compared to WCT for all measurements performed in this study. Consequently, more accurate radiation treatment for the intracranial regions can be expected when the proper image similarity evaluation introduced in this study is performed.

Comparison of spinal Stereotactic Body Radiotherapy (SBRT) planning techniques: intensity-modulated radiation therapy, modulated arc therapy, and helical tomotherapy.

Stereotactic body radiotherapy (SBRT) delivers a highly conformal, hypofractionated radiation dose to a small target with minimal radiation applied to the surrounding areas. Therefore, using the proper treatment planning techniques for SBRT is important. Intensity modulation techniques, such as static intensity-modulated radiation therapy (IMRT), modulated arc therapy (mARC), and helical tomotherapy (HT), are useful for spinal SBRT because of a rapid dose fall-off and spinal cord avoidance. This study compared the planning characteristics for hypofractionated spinal SBRT administered using 3 treatment techniques. The factors evaluated for spinal SBRT planning were dose coverage, cord avoidance, target conformity, homogeneity, and dose spillage. Target coverage was 82.74% ± 3.35%, 80.92% ± 0.81%, and 85.01% ± 7.27% for IMRT, mARC, and HT, respectively. HT was therefore a powerful technique with respect to target coverage. The spinal cord dose for HT (mean, 1763.96 cGy; standard deviation [SD], 164.48) was significantly different from those for mARC (mean, 1991.75 cGy; SD, 248.00) and IMRT (mean, 2053.24 cGy; SD, 164.48). In addition, the partial spinal cord volume at 2000 cGy for HT (mean, 0.12 cc, SD, 0.01) was significantly different from those for IMRT and mARC (0.50 ± 0.10 cc and 0.56 ± 0.25 cc, respectively). The conformity index was 1.30 ± 0.12, 1.08 ± 0.05, and 1.36 ± 0.23 for IMRT, mARC, and HT planning, respectively. mARC showed the highest conformity (p = 0.000). HT used a narrow field fan beam and exhibited remarkable improvement of target coverage and cord dose, offering an important benefit to spinal SBRT. mARC had the highest target conformity and better high- and intermediate-dose spillage than HT and IMRT did, respectively. These planning techniques have different advantages. In the case of spine SBRT, HT should be used for cord avoidance. In some cases, such as for a short treatment duration when the patient is considered to be in a poor general condition, mARC can be used.

Stereotactic radiosurgery for brain metastasis in non-small cell lung cancer.

PURPOSE: Stereotactic radiosurgery (SRS) has been introduced for small-sized single and oligo-metastases in the brain. The aim of this study is to assess treatment outcome, efficacy, and prognostic variables associated with survival and intracranial recurrence. MATERIALS AND METHODS: This study retrospectively reviewed 123 targets in 64 patients with non-small cell lung cancer (NSCLC) treated with SRS between January 2006 and December 2012. Treatment responses were evaluated using magnetic resonance imaging. Overall survival (OS) and intracranial progression-free survival (IPFS) were determined. RESULTS: The median follow-up was 13.9 months. The median OS and IPFS were 14.1 and 8.9 months, respectively. Fifty-seven patients died during the follow-up period. The 5-year local control rate was achieved in 85% of 108 evaluated targets. The 1- and 2-year OS rates were 55% and 28%, respectively. On univariate analysis, primary disease control (p < 0.001), the Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs. 2; p = 0.002), recursive partitioning analysis class (1 vs. 2; p = 0.001), and age (<65 vs. ≥65 years; p = 0.036) were significant predictive factors for OS. Primary disease control (p = 0.041) and ECOG status (p = 0.017) were the significant prognostic factors for IPFS. Four patients experienced radiation necrosis. CONCLUSION: SRS is a safe and effective local treatment for brain metastases in patients with NSCLC. Uncontrolled primary lung disease and ECOG status were significant predictors of OS and intracranial failure. SRS might be a tailored treatment option along with careful follow-up of the intracranial and primary lung disease status.

Immune Reconstitution Kinetics following Intentionally Induced Mixed Chimerism by Nonmyeloablative Transplantation.

Establishing mixed chimerism is a promising approach for inducing donor-specific transplant tolerance. The establishment and maintenance of mixed chimerism may enable long-term engraftment of organ transplants while minimizing the use of immunosuppressants. Several protocols for inducing mixed chimerism have been reported; however, the exact mechanism underlying the development of immune tolerance remains to be elucidated. Therefore, understanding the kinetics of engraftment during early post-transplant period may provide insight into establishing long-term mixed chimerism and permanent transplant tolerance. In this study, we intentionally induced allogeneic mixed chimerism using a nonmyeloablative regimen by host natural killer (NK) cell depletion and T cell-depleted bone marrow (BM) grafts in a major histocompatibility complex (MHC)-mismatched murine model and analyzed the kinetics of donor (C57BL/6) and recipient (BALB/c) engraftment in the weeks following transplantation. Donor BM cells were well engrafted and stabilized without graft-versus-host disease (GVHD) as early as one week post-bone marrow transplantation (BMT). Donor-derived thymic T cells were reconstituted four weeks after BMT; however, the emergence of newly developed T cells was more obvious at the periphery as early as two weeks after BMT. Also, the emergence and changes in ratio of recipient- and donor-derived NKT cells and antigen presenting cells (APCs) including dendritic cells (DCs) and B cells were noted after BMT. Here, we report a longitudinal analysis of the development of donor- and recipient-originated hematopoietic cells in various lymphatic tissues of intentionally induced mixed chimerism mouse model during early post-transplant period. Through the understanding of immune reconstitution at early time points after nonmyeloablative BMT, we suggest guidelines on intentionally inducing durable mixed chimerism.

High-dose radiotherapy using helical tomotherapy for vertebral metastasis: early clinical outcomes and cord dose specification.

OBJECTIVE: For several decades, radiotherapy has been widely used to treat metastatic vertebral tumors. This study was designed to assess the feasibility and early clinical outcomes of high-dose radiotherapy to treat such tumors, using helical tomotherapy. METHODS: Between June 2009 and December 2011, 51 sites in 36 patients were treated with high-dose radiotherapy using helical tomotherapy for vertebral metastasis. Treatment outcomes and dosimetric analyses of spinal cord were retrospectively evaluated. RESULTS: Median follow-up was 11.5 months (range, 6-34.6) for surviving patients. The median total dose and the number of fractions in the primary helical tomotherapy arm were 2700 cGy and 3 fractions, respectively. Actuarial 6-month local control rates were 85.7%, and symptomatic vertebral compression fractures developed in five patients after a median of 4.2 (range, 2.9-5.7) months. Among 13 patients with 19 metastatic sites who showed pre-treatment impairment in neurologic function, five patients (with seven sites) in whom symptoms were mild showed improvement in neuronal function. The median pre-treatment pain visual analog scale score of 7 decreased to a median of 3 after helical tomotherapy (P < 0.001) at a median of 1 month (range, 0.5-3.2) of follow-up. No significant morbidity developed during follow-up except for one grade 3 esophagitis. CONCLUSIONS: The use of helical tomotherapy to treat metastatic vertebral tumors appears to be both safe and reliable in terms of local tumor control and early pain relief. Local progression and the risk of compression fracture in patients with pre-existing spinal instability remain the principal factors of limiting improved clinical and functional outcomes. Optimal dose-fractionation schemes and appropriate patient selection are required to achieve better outcomes with high-dose radiotherapy using helical tomotherapy.

Determination of the α/ß ratio for the normal liver on the basis of radiation-induced hepatic toxicities in patients with hepatocellular carcinoma.

BACKGROUND: The purpose of this study was to determine the α/ß ratio for normal liver with hepatitis by analyzing the toxicity data from patients with unresectable hepatocellular carcinoma treated with helical tomotherapy. METHODS: Between March 2006 and February 2012, 98 patients were eligible for this study. 66 patients received 45-50 Gy in 4.5-5 Gy fractions (Group A) and 32 patients received 36-60 Gy in 2.5-3 Gy fractions (Group B). Radiation-induced hepatic toxicity was defined as an increase of at least 2 points in the Child-Pugh score within 4 months of completing helical tomotherapy. We attempted to find the statistically significant parameters in the 2 groups using α/ß ratios of 2, 4, 6, 8, or 10, and compared the estimated probability curves of each significant parameter. We hypothesized that the α/ß ratio associated with the best matches for the curves between the 2 groups would be equivalent to the α/ß ratio for the normal liver. RESULTS: When using an α/ß ratio of 2 or 4, different parameters were found to be statistically significant in a multivariate analysis (Group A: VBED30 for α/ß ratio=2 and VBED25 for α/ß ratio=4, Group B: VBED25 for α/ß ratio=2 and VBED20 for α/ß ratio=4). When using an α/ß ratio of 6, 8, or 10, VBED20 was found to be a statistically significant parameter in both groups. Comparison of the estimated probability curve of each significant parameter between the groups revealed that an α/ß ratio of 8 resulted in the best matches. CONCLUSIONS: We suggest that the α/ß ratio of the normal liver with hepatitis is 8. We hope that previously reported parameters and their values can be effectively used in different fractionation schemes by calculating the biologically effective dose using an α/ß ratio of 8.

Long-term clinical experience of high-dose ablative lung radiotherapy: high pre-treatment [18F]fluorodeoxyglucose-positron emission tomography maximal standardized uptake value of the primary tumor adversely affects treatment outcome.

PURPOSE: The aim of this study was to report the long-term clinical experience with lung stereotactic ablative radiotherapy (SABR). METHODS: Between April 2004 and December 2011, 58 of 92 consecutive lung SABR cases were treated with a curative purpose and were eligible for inclusion. Forty patients were treated for primary lung cancer, and eighteen were treated for locally confined recurrent tumors. The majority of the cases were medically inoperable (65.5%). A median five fractions with a total dose of 30-60Gy were prescribed to the planned target volume. We routinely performed an image-guided respiratory gating technique or four-dimensional computed tomography to minimize set-up errors and accurately determine target volumes. RESULTS: The median follow-up was 23.8 (range, 1.5-77.2) months. The median age of the entire cohort was 73 (range, 48-90) years. The median gross tumor volume and maximal tumor diameter were 20 (range, 0.5-189.7) ml and 2.2 (range, 0.7-5.9) cm, respectively. The two-year local control (LC) rate was 92.1%, and the major pattern of failure was distant metastasis (25.9%). A high pre-treatment maximal standardized uptake value (mSUV) of the primary tumor significantly and adversely affected LC, local relapse-free survival, distant metastasis-free survival, cause-specific survival and overall survival. The toxicity rates (≥grade 2) were 34.5% and 35% for the central and peripheral tumors, respectively, and one grade 5 toxic event (death due to massive hemoptysis) occurred in a centrally located tumor at 16.7 months post-SABR. CONCLUSIONS: Lung SABR remains an effective and safe local treatment modality. Pre-treatment mSUV may be a helpful parameter to select patients requiring higher radiation doses and adjuvant systemic therapy for lung SABR.

Dosimetric parameter predicting the deterioration of hepatic function after helical tomotherapy in patients with unresectable locally advanced hepatocellular carcinoma.

BACKGROUND: The purpose of this study was to identify parameters capable of predicting the deterioration of hepatic function after helical tomotherapy in patients with unresectable locally advanced hepatocellular carcinoma. METHODS: Between March 2006 and February 2012, 72 patients were eligible for this study. All patients received hypofractionated radiotherapy using the TomoTherapy Hi-Art (TomoTherapy, Madison, WI, USA) at Seoul St. Mary's Hospital and Incheon St. Mary's Hospital, the Catholic University of Korea. The radiation dose was a median 50 Gy (range: 40-50 Gy) in 10 fractions to 95% of the planning target volume. Radiation-induced hepatic toxicity was defined as an increase of at least 2 points in the Child-Pugh (CP) score within 3 months after completion of helical tomotherapy. RESULTS: An increase of at least 2 points in the CP score occurred in 32 of the 72 patients (44.4%). Multivariate logistic regression analysis revealed that pretreatment CP class and V15Gy were significant parameters associated with an increase in CP score (p = 0.009 and p < 0.001, respectively). The area under receiver operating characteristic curve was 0.863 for V15Gy (p < 0.001). For V15Gy, with a cutoff value of 43.2%, the accuracy was 0.806 (58/72) with a sensitivity of 0.938 and a specificity of 0.725. CONCLUSIONS: An increase of at least 2 points in the CP score is a radiation dose-limiting factor, and the non-target normal liver receiving a dose more than 15 Gy (V15Gy) should be <43.2% to reduce the risk of the deterioration of hepatic function.

The technical feasibility of an image-guided intensity-modulated radiotherapy (IG-IMRT) to perform a hypofractionated schedule in terms of toxicity and local control for patients with locally advanced or recurrent pancreatic cancer.

BACKGROUND: The purpose of this study was to evaluate the technical feasibility of an image-guided intensity modulated radiotherapy (IG-IMRT) using involved-field technique to perform a hypofractionated schedule for patients with locally advanced or recurrent pancreatic cancer. METHODS: From May 2009 to November 2011, 12 patients with locally advanced or locally recurrent pancreatic cancer received hypofractionated CCRT using TomoTherapy Hi-Art with concurrent and sequential chemotherapy at Seoul St. Mary's Hospital, the Catholic University of Korea. The total dose delivered was 45 Gy in 15 fractions or 50 Gy in 20 fractions. The target volume did not include the uninvolved regional lymph nodes. Treatment planning and delivery were performed using the IG-IMRT technique. The follow-up duration was a median of 31.1 months (range: 5.7-36.3 months). RESULTS: Grade 2 or worse acute toxicities developed in 7 patients (58%). Grade 3 or worse gastrointestinal and hematologic toxicity occurred in 0% and 17% of patients, respectively. In the response evaluation, the rates of partial response and stable disease were 58% and 42%, respectively. The rate of local failure was 8% and no regional failure was observed. Distant failure was the main cause of treatment failure. The progression-free survival and overall survival durations were 7.6 and 12.1 months, respectively. CONCLUSION: The involved-field technique and IG-IMRT delivered via a hypofractionated schedule are feasible for patients with locally advanced or recurrent pancreatic cancer.

Long-term outcome and toxicity of hypofractionated stereotactic body radiotherapy as a boost treatment for head and neck cancer: the importance of boost volume assessment.

BACKGROUND: The aim of this study was to report the long-term clinical outcomes of patients who received stereotactic body radiotherapy (SBRT) as a boost treatment for head and neck cancer. MATERIALS AND METHODS: Between March 2004 and July 2007, 26 patients with locally advanced, medically inoperable head and neck cancer or gross residual tumors in close proximity to critical structures following head and neck surgery were treated with SBRT as a boost treatment. All patients were initially treated with standard external beam radiotherapy (EBRT). SBRT boost was prescribed to the median 80% isodose line with a median dose of 21 (range 10-25) Gy in 2-5 (median, 5) fractions. RESULTS: The median follow-up after SBRT was 56 (range 27.6 - 80.2) months. The distribution of treatment sites in 26 patients was as follows: the nasopharynx, including the base of the skull in 10 (38.5%); nasal cavity or paranasal sinus in 8 (30.8%); periorbit in 4 (15.4%); tongue in 3 (11.5%); and oropharyngeal wall in 1 (3.8%). The median EBRT dose before SBRT was 50.4 Gy (range 39.6 - 70.2). The major response rate was 100% with 21 (80.8%) complete responses (CR). Severe (grade ≥ 3) late toxicities developed in 9 (34.6%) patients, and SBRT boost volume was a significant parameter predicting severe late complication. CONCLUSIONS: The present study demonstrates that a modern SBRT boost is a highly efficient tool for local tumor control. However, we observed a high frequency of serious late complications. More optimized dose fractionation schedule and patient selection are required to achieve excellent local control without significant late morbidities in head and neck boost treatment.

The effect of metallic implants on radiation therapy in spinal tumor patients with metallic spinal implants.

The aim of this study was to evaluate the effect of metallic implants on the dose calculation for radiation therapy in patients with metallic implants and to find a way to reduce the error of dose calculation. We made a phantom in which titanium implants were inserted into positions similar to the implant positions in spinal posterior/posterolateral fusion. We compared the calculated dose of the treatment planning systems with the measured dose in the treatment equipment. We used 3 kinds of computed tomography (CT) (kilovoltage CT, extended-scaled kilovoltage CT, and megavoltage CT) and 3 kinds of treatment equipment (ARTISTE, TomoTherapy Hi-Art, and Cyberknife). For measurement of doses, we used an ionization chamber and Gafchromic external beam therapy film. The absolute doses that were measured using an ionization chamber at the isocenter in the titanium phantom were on average 1.9% lower than those in the reference phantom (p = 0.002). There was no statistically significant difference according to the kinds of CT images, the treatment equipment, and the size of the targets. As the distance from the surface of the titanium implants became closer, the measured doses tended to decrease (p < 0.001), and this showed a statistically significant difference among the kinds of CT images: the effect of metallic implants was less in the megavoltage CT than in the kilovoltage CT or the extended-scaled kilovoltage CT. The error caused by the titanium implants was beyond a clinically acceptable range. To reduce the error of dose calculation, we suggest that the megavoltage CT be used for planning. In addition, it is necessary to consider the distance between the titanium implants and the targets or the organs at risk to prescribe the dose for the target and the dose constraint for the organs at risk.