Nationwide multi-institutional retrospective analysis of high-dose-rate brachytherapy combined with external beam radiotherapy for localized prostate cancer: An Asian Prostate HDR-BT Consortium.

PURPOSE: To report outcomes and risk factors of high-dose-rate (HDR) brachytherapy combined with external beam radiotherapy with or without androgen deprivation therapy (ADT) in prostate cancer patients. MATERIALS AND METHODS: This multi-institutional retrospective analysis comprised 3424 patients with localized prostate cancer at 16 Asian hospitals. One-thirds (27.7%) of patients received only neoadjuvant ADT, whereas almost half (49.5%) of patients received both neoadjuvant and adjuvant ADT. Mean duration of neoadjuvant and adjuvant ADT were 8.6 months and 27.9 months, respectively. Biochemical failure was defined by Phoenix ASTRO consensus. Biochemical control rate, clinical disease-free survival (cDFS), cause-specific survival, and overall survival (OS) were calculated. RESULTS: Median followup was 66 months. Ten-year biochemical control, cDFS, cause-specific survival, and OS rate were 81.4%, 81.0%, 97.2%, and 85.6%, respectively. Receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for biochemical control, cDFS, and OS, but pelvic irradiation was detected as an adverse factor for cause-specific survival, and OS. Ten-year cumulative rates of late Grade ≥2 genitourinary and gastrointestinal toxicities were 26.8% and 4.1%, respectively; receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for preventing both toxicities. CONCLUSIONS: HDR combined with external beam radiotherapy was an effective and safe treatment for localized prostate cancer. Combination of long-term ADT was suggested to be necessary, even for HDR brachytherapy, and was useful in suppressing late toxicities. Meanwhile, pelvic irradiation was suggested to have an adverse effect on OS of our study population.

Three-dimensional conformal arc radiotherapy using a C-arm linear accelerator with a computed tomography on-rail system for prostate cancer: clinical outcomes.

BACKGROUND: We report the feasibility and treatment outcomes of image-guided three-dimensional conformal arc radiotherapy (3D-CART) using a C-arm linear accelerator with a computed tomography (CT) on-rail system for localized prostate cancer. METHODS AND MATERIALS: Between 2006 and 2011, 282 consecutive patients with localized prostate cancer were treated with in-room CT-guided 3D-CART. Biochemical failure was defined as a rise of at least 2.0 ng/ml beyond the nadir prostate-specific antigen level. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: A total of 261 patients were analyzed retrospectively (median follow-up: 61.6 months). The median prescribed 3D-CART dose was 82 Gy (2 Gy/fraction, dose range: 78-86 Gy), and 193 of the patients additionally received hormonal therapy. The 5-year overall survival rate was 93.9 %. Among low-, intermediate-, and high-risk patients, 5-year rates of freedom from biochemical failure were 100, 91.5 and 90.3 %, respectively. Rates of grade 2-3 late gastrointestinal and genitourinary toxicities were 2.3 and 11.4 %, respectively. No patient experienced late grade 4 or higher toxicity. CONCLUSIONS: In-room CT-guided 3D-CART was feasible and effective for localized prostate cancer. Treatment outcomes were comparable to those previously reported for intensity-modulated radiotherapy.

NUT Midline Carcinoma in Elderly Patients: Usefulness of 18F-FDG PET/CT for Treatment Assessment.

Nuclear protein in testis (NUT) midline carcinoma is a rare disease that generally arises in adolescents and young adults. However, we encountered a rare NUT midline carcinoma case in an elderly patient. F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (PET/CT) studies were performed before and during the treatment course. In this case, the initial PET/CT study revealed locoregional hypermetabolism in the mediastinal lesion. After then, the interim PET/CT study indicated a clear diminishing response to the initial treatment, whereas the residual masses were morphologically observable. Nuclear imaging may allow visualization of the therapeutic effect of antineoplastic therapies in both young and elderly patients.

[Additional external radiotherapy to multiple metastases originating from thymic neuroendocrine tumor following peptide receptor radionuclide therapy: a case report].

We describe the case of a 60-year-old man suffering from an advanced thymic neuroendocrine tumor with left supraclavicular lymph node and multiple bone metastases. The patient initially underwent systemic therapy with somatostatin analogues. Thereafter, peptide receptor radionuclide therapy (PRRT) was considered because the lesions had remained stable despite the pharmacological therapy. PRRT was performed 10 months after the initial treatment in a European hospital. Eighteen months after the treatment, cranial nerve palsy arising from skull base metastases and Horner's syndrome induced by left supraclavicular lymph node metastases became exacerbated. Therefore, a course of external radiotherapy was performed with palliative intent in our hospital. During the radiotherapy planning, the biodistribution of 111In-octreotide was examined to determine whether the absorbed dose of the previous PRRT was acceptable. As a result, external radiotherapy was performed, and an acute radiation reaction was observed; the severity of the reaction was typical of reactions to neck radio-therapy. The treatment course of the present case was considered to be instructive because PRRT cannot be performed in Japan at present.

Surgical therapy and chemoradiotherapy for postoperative recurrent esophageal cancer.

BACKGROUND/AIMS: A retrospective analysis of therapeutic modalities used in postoperative recurrent esophageal cancer. METHODOLOGY: Among 43 esophageal cancer patients who underwent esophagectomy between 2003 and 2010, recurrence was found in 15. Best supportive care was given to two patients and another patient was referred to another hospital. The remaining 12 patients were treated by the following modalities: Surgical resection: 2 cases; chemoradiotherapy: 7 cases; chemotherapy: 2 cases; and radiotherapy: 1 case. The median survival time, 1-year survival rates, and response rates were examined. Data from 13 esophageal cancer patients who underwent chemoradiotheray as an initial therapy in the same period were collected and compared with recurrent cases treated with chemoradiotherapy. RESULTS: For all 12 patients, the median overall survival time was 19.5 months, and the 1-year survival rate was 83%. Among 7 chemoradiotherapy patients, the response rate was 57%. The median survival time was 23 months, and the 1-year survival rate was 86%. The response rate of 13 patients receiving chemoradiotherapy as an initial therapy was 69%. The median overall survival time was 12 months and the 1-year survival rate was 54%. CONCLUSIONS: Re-operation and chemoradiotherapy for recurrent esophageal cancer might be as effective as the same treatment used initially.

Converging stereotactic radiotherapy using kilovoltage X-rays: experimental irradiation of normal rabbit lung and dose-volume analysis with Monte Carlo simulation.

PURPOSE: To validate the feasibility of developing a radiotherapy unit with kilovoltage X-rays through actual irradiation of live rabbit lungs, and to explore the practical issues anticipated in future clinical application to humans through Monte Carlo dose simulation. METHODS AND MATERIALS: A converging stereotactic irradiation unit was developed, consisting of a modified diagnostic computed tomography (CT) scanner. A tiny cylindrical volume in 13 normal rabbit lungs was individually irradiated with single fractional absorbed doses of 15, 30, 45, and 60 Gy. Observational CT scanning of the whole lung was performed every 2 weeks for 30 weeks after irradiation. After 30 weeks, histopathologic specimens of the lungs were examined. Dose distribution was simulated using the Monte Carlo method, and dose-volume histograms were calculated according to the data. A trial estimation of the effect of respiratory movement on dose distribution was made. RESULTS: A localized hypodense change and subsequent reticular opacity around the planning target volume (PTV) were observed in CT images of rabbit lungs. Dose-volume histograms of the PTVs and organs at risk showed a focused dose distribution to the target and sufficient dose lowering in the organs at risk. Our estimate of the dose distribution, taking respiratory movement into account, revealed dose reduction in the PTV. CONCLUSIONS: A converging stereotactic irradiation unit using kilovoltage X-rays was able to generate a focused radiobiologic reaction in rabbit lungs. Dose-volume histogram analysis and estimated sagittal dose distribution, considering respiratory movement, clarified the characteristics of the irradiation received from this type of unit.

Extrapulmonary soft-tissue fibrosis resulting from hypofractionated stereotactic body radiotherapy for pulmonary nodular lesions.

PURPOSE: To clarify the incidence, symptoms, and timing of extrapulmonary fibrosis developing after hypofractionated stereotactic body radiotherapy. PATIENTS AND METHODS: We analyzed 379 consecutive patients who underwent stereotactic body radiotherapy for lung tumors at four institutions between February 2001 and March 2007. The median follow-up time was 29 months (range, 1-72). We investigated the subjective and objective characteristics of the extrapulmonary masses, redelineated the origin tissue of each on the treatment planning computed tomography scan, and generated dose-volume histograms. RESULTS: In 9 patients (2.4%), extrapulmonary masses were found 3-36 months (median, 14) after irradiation. Coexisting swelling occurred in 3 patients, chest pain in 2, thumb numbness in 1, and arm edema in 1 patient. Extrapulmonary masses occurred in 5 (5.4%) of 92 and 4 (1.4%) of 287 patients irradiated with a 62.5-Gy and 48.0-Gy isocenter dose, respectively. The mean and maximal dose to the origin tissue was 25.8-53.9 Gy (median, 43.7) and 47.5-62.5 Gy (median, 50.2), respectively. In 5 of 9 patients, the standardized uptake values on 18F-fluorodeoxyglucose-positron emission tomography was 1.8-2.8 (median, 2.2). Percutaneous needle biopsy was performed in 3 patients, and all the specimens showed benign fibrotic changes without malignant cells. CONCLUSION: All patients should be carefully followed after stereotactic body radiotherapy. The findings of any new lesion should prompt an assessment for radiation-induced extrapulmonary fibrosis before an immediate diagnosis of recurrence is made. Careful beam-shape modification and dose prescription near the thoracic outlet are required to prevent forearm neuropathy and lymphedema.

Intense accumulation of Tc-99m MDP in pericardial metastasis from breast cancer.

Extraosseous uptake often seen on Tc-99m methylene diphosphonate bone scintigraphy has clinical significance. In a routine follow-up study on a 54-year-old female patient with breast cancer, we encountered a rare finding of pericardial metastasis clearly demonstrated by Tc-99m methylene diphosphonate bone scintigraphy. This incidental finding of increased uptake in the periphery of the cardiac contour on a bone scan reflects radionuclide accumulation in pericardium, myocardium, or pericardial effusion itself. In our case, an additional computed tomography examination of the chest was useful for making the definitive diagnosis of dystrophic calcification of the pericardium.

Differences in the definition of internal target volumes using slow CT alone or in combination with thin-slice CT under breath-holding conditions during the planning of stereotactic radiotherapy for lung cancer.

PURPOSE: To investigate how the delineations of the internal target volume (ITV) made from 'slow' CT alter with reference to 'thin-slice' CT. MATERIALS AND METHODS: Thin-slice CT images taken under breath-holding conditions and slow CT images taken under shallow-breathing conditions (8s/image) of 11 lung cancers were used for this study. Five radiation oncologists delineated ITV of the 11 lesions using slow CT images (ITV1), and then redefined them with reference to thin-slice CT images (ITV2). SD-images (standard deviation image) were created for all patients from ITV images in order to visualize the regional variation of the ITVs. RESULTS: The mean value of ITV2 was smaller than that initially defined by ITV1. There was no significant change in ITV1 and ITV2 between operators with regard to standard deviation in volume. There was a significant difference in the distribution of the ratio of ITV1 to ITV2 obtained on thin-slice CTs between cases with and without ground glass opacity. In cases without ground glass opacity there was a tendency for ITV2 to have a smaller volume than ITV1. CONCLUSIONS: Combined use of slow CT and thin-slice CT in delineation of ITV contours appeared to be useful in making adjustments for obscured tumor images caused by respiratory movement.

Experimental stereotactic irradiation of normal rabbit lung: computed tomographic analysis of radiation injury and the histopathological features.

PURPOSE: The aim of this study was to establish an animal experimental model of pulmonary stereotactic irradiation and clarify the morphological patterns of pulmonary radiation injury with computed tomography and the histopathological features. MATERIALS AND METHODS: Tiny spherical regions in the lungs of seven anesthetized rabbits were irradiated stereotactically with a single fractional dose of 21-60 Gy. Subsequently, the irradiated lungs were observed biweekly with computed tomography (CT) for 24 weeks. Radiation injury of the lung was examined histopathologically in one specimen. RESULTS: Localized hypodense changes were observed 7-15 weeks after irradiation in three rabbits irradiated with 60 Gy, and the findings persisted beyond that time. The electron density ratios in the lung fields obtained from the CT images were shown to be decreasing, corresponding to the hypodensity changes. No clear increased density opacity was observed in any rabbit in the 60-Gy irradiated group. Severe localized fibrotic change was observed in the histopathological specimens. CONCLUSION: Specific localized hypodensity changes were found in only three rabbits irradiated with 60 Gy, the highest dose we employed.

Interface software for DOSXYZnrc Monte Carlo dose evaluation on a commercial radiation treatment planning system.

PURPOSE: As the conventional graphical user interface (GUI) associated with DOSXYZnrc or BEAMnrc is unable to define specific structures such as gross tumor volume (GTV) on computed tomography (CT) data, the quantitative analysis of doses in the form of dose-volume histograms (DVHs) is difficult. The purpose of this study was to develop an interface that enables us to analyze the results of DOSXYZnrc output with a commercial radiation treatment planning (RTP) system and to investigate the validity of the system. MATERIALS AND METHODS: Interface software to visualize three-dimensional radiotherapy Monte Carlo (MC) dose data from DOSXYZnrc on the XiO RTP system was developed. To evaluate the interface, MC doses for a variety of photon energies were calculated using the CT data of a thorax phantom and a uniform phantom as well as data from patients with lung tumors. RESULTS: The dose files were analyzed on the XiO RTP system in the form of isodose distributions and DVHs. In all cases, the XiO RTP system perfectly displayed the MC doses for quantitative evaluation in the form of differential and integral DVHs. CONCLUSION: Three-dimensional display of DOSXYZnrc doses on a dedicated RTP system could provide all the existing facilities of the system for quantitative dose analysis.

Rotational and translational reproducibility of newly developed Leksell frame-based relocatable fixation system.

PURPOSE: The aim of this study was to evaluate three-dimensional movement of the cranium in a relocatable frame using positions of anatomical landmarks obtained from repeated quality-assurance (QA) computed tomography (CT) studies. MATERIALS AND METHODS: We analyzed 17 series of QA-CT data representing five patients who underwent stereotactic radiotherapy for treatment of acoustic neurinoma. Helical-CT scans with 1-mm collimation were obtained at the time of treatment planning and during the course of treatment. The right and left short processes of the incus and the top of the crista galli were used as the three anatomical reference points. RESULTS: Fluctuations in distance among the reference points were all <1 mm. The translational displacements for these points were <2 mm, with standard deviations (SD) of <2 mm. A plane that included all three reference points was defined as the reference plane. To investigate the direction of cranial rotation for each QA-CT scan, unit normal vectors of the reference plane were obtained. Three-dimensional analyses indicated that cranial rotation was greatest along the X-axis, followed by the Y-axis, with the least rotation along the Z-axis. CONCLUSION: The result suggested that movement of the craniocaudal axis in the sagittal plane was a major factor behind displacement of the cranium.

Investigations of different kilovoltage X-ray energy for three-dimensional converging stereotactic radiotherapy system: Monte Carlo simulations with CT data.

We are investigating three-dimensional converging stereotactic radiotherapy (3DCSRT) with suitable medium-energy x rays as treatment for small lung tumors with better dose homogeneity at the target. A computed tomography (CT) system dedicated for non-coplanar converging radiotherapy was simulated with BEAMnrc (EGS4) Monte-Carlo code for x-ray energy of 147.5, 200, 300, and 500 kilovoltage (kVp). The system was validated by comparing calculated and measured percentage of depth dose in a water phantom for the energy of 120 and 147.5 kVp. A thorax phantom and CT data from lung tumors (<20 cm3) were used to compare dose homogeneities of kVp energies with MV energies of 4, 6, and 10 MV. Three non-coplanar arcs (0 degrees and +/-25 degrees ) around the center of the target were employed. The Monte Carlo dose data format was converted to the XiO RTP format to compare dose homogeneity, differential, and integral dose volume histograms of kVp and MV energies. In terms of dose homogeneity and DVHs, dose distributions at the target of all kVp energies with the thorax phantom were better than MV energies, with mean dose absorption at the ribs (human data) of 100%, 85%, 50%, 30% for 147.5, 200, 300, and 500 kVp, respectively. Considering dose distributions and reduction of the enhanced dose absorption at the ribs, a minimum of 500 kVp is suitable for the lung kVp 3DCSRT system.

Small lung tumors: long-scan-time CT for planning of hypofractionated stereotactic radiation therapy--initial findings.

PURPOSE: To prospectively use long-scan-time computed tomography (CT) to visualize the trajectory of tumor movements or the internal target volume. MATERIALS AND METHODS: The study was approved by the institutional review board. Written informed consent was obtained from participants after the study and the role of procedures were explained fully. During the planning of stereotactic radiation therapy for 10 patients (nine men, one woman; mean age, 77 years; range, 69-89 years) with small lung tumors (mean volume, 9.0 cm3; range, 3.6-24.9 cm3), fluoroscopic imaging, long-scan-time CT, and thin-section CT were performed. The tumor and the partial-volume-averaging effects that resulted from tumor movement were delineated on each section at long-scan-time CT performed during the patient's steady breathing with scan time of 8 seconds per image. Visualized internal target volume was defined by integrating the sections. A simple model was examined for estimating internal target volume on the basis of respiratory motion and gross target volume delineated on thin-section CT images. Visualized internal target volume and estimated internal target volume were compared quantitatively and graphically. The Mann-Whitney test was used to analyze the relation between gross target volume delineated on thin-section CT images and the ratio of visualized internal target volume to the defined gross target volume. RESULTS: The correlation coefficient between visualized internal target volume and estimated internal target volume was r = 0.98 (P < .001). The mean relative error +/- standard deviation was 1.9% +/- 19.0 (range, -11.0% to 56.4%). Excluding one case with an irregularly shaped tumor (56.4%), the mean relative error was -4.1% +/- 4.1. In patients with small tumors (defined gross target volume, < or = 10 cm3), the ratio of the visualized internal target volume to the defined gross tumor volume was significantly larger than that in patients with larger tumors (1.2-2.0 vs 1.0-1.2; P < .05). In some cases in which marginal spiculation depicted on thin-section CT images was blurred on long-scan-time CT images, the blurred area was erroneously excluded from the target volume. CONCLUSION: In most cases, values for visualized internal target volume and estimated internal target volume were similar and long-scan-time CT depicted virtually the entire tumor trajectory.

Effects of density changes in the chest on lung stereotactic radiotherapy.

To experimentally and theoretically evaluate dose distribution during lung stereotactic radiotherapy, we investigated the relative electron densities in lung and tumor tissues using X-ray computed tomography images obtained from 30 patients in three breathing states: free breathing, inspiration breath-hold, and expiration breath-hold. We also calculated dose distribution using Monte Carlo simulation for lung tissue with two relative electron densities. The effect of changes in relative electron density on dose distribution in lung tissue was evaluated using calculated differential and integral dose volume histograms. The relative electron density of lung tissue was 0.22 in free breathing, 0.23 in shallow expiration, and 0.17 in shallow inspiration, and there was a tendency for relative electron density to decrease with age. The relative electron density of tumor tissue was approximately 0.9, with little variation due to differences in breathing state. As the relative electron density of lung tissue decreases, the low-dose region expands and leads to changes in the marginal dose.

Measurement of beam-axis displacement from the isocenter during three-dimensional conformal radiosurgery with a micro-multileaf collimator.

We describe the displacement of the beam-axis from the planning isocenter in clinical situations during three-dimensional conformal radiosurgery using an Acculeaf bi-directional micro-multileaf collimator. The displacements were recorded for 64 ports using a video imaging system and a stereotactic arc. The mean displacement was 0.41+/-0.25 mm.

Monitoring of response to radiation therapy for human tumor xenografts using 99mTc-HL91 (4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime).

PURPOSE: Oxygenation status of tumor tissue is an important factor to discriminate it with respect to its radiosensitivity. 99mTc-4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime (99mTc-HL91) is retained in hypoxic tissues, making it possible to use it as hypoxic imaging agent. We evaluated if the accumulation of 99mTc-HL91 in tumors could aid in the prediction of sensitivity of radiation therapy of cancers. METHODS: Human tumors (the gastric cancer cell line: MKN45, the epidermoid carcinoma cell line: KB-31, and the lung adenocarcinoma cell line: HLC) were xenografted into the thigh of athymic mice and irradiated with a 4 MV linear accelerator. Tumor growth was measured and 99mTc-HL91 uptakes in tumors were determined by serial imaging, biodistribution, and autoradiography. RESULTS: 99mTc-HL91 uptake (ratio of ROItumor to ROIwhole body) in HLC ranged from 1.1 to 8.0%, and it did not show any response to radiation therapy. Major variations were observed in 99mTc-HL91 accumulation in MKN45 and KB-31; from 0.7 to 4.7%, and from 1.0 to 7.3%, respectively. Some tumors responded to radiotherapy, while others did not. Tumor response was not dependent on the 99mTc-HL91 uptake, tumor size or radiation dose. Comparing 99mTc-HL91 uptake in tumors before (B) and after (A) their radiation, uptake (B) was always smaller than uptake (A) for HLC, and they did not respond to irradiation at all. For MKN45 and KB-31, tumors responded to radiation when their uptake (A) was not higher than uptake (B). In contrast, the tumors continued to grow when their uptake (A) was higher than uptake (B). Sequential 99mTc-HL91 imaging of KB-31 and their autoradiography indicated that tumors whose 99mTc-HL91 uptakes was increased post irradiation were composed of mainly hypoxic cells. On the other hand, many viable areas were observed in tumors when the increase in 99mTc-HL91 uptake was relatively small. CONCLUSION: 99mTc-HL91 uptake in tumors did not always relate to their sensitivities to radiation therapy. Sequential 99mTc-HL91 imagings post irradiation showed that the increase in 99mTc-HL91 uptake in tumors predicted a poor response to radiation therapy, and that a decrease or no change suggested that radiation therapy would be effective. Monitoring by 99mTc-HL91 imaging is a good tool to predict the radiosentivities of tumors.