Takatsugu Kawase

The modified tangential irradiation technique for breast cancer: how to cover the entire axillary region

PURPOSE The two-portal tangential irradiation technique has usually been applied to breast cancer patients after breast-conserving surgery (1, 2) and is expected to irradiate the axillary lymph node region to some extent (3). We investigated the range of the axillary region covered by this technique and tried to devise an optimal irradiation technique (modified tangential irradiation) that would cover the axillary lymph node region properly. METHODS AND MATERIALS We checked the status of the surgical clips left at axillary lymph node sites by reviewing the simulator films and planning CT scans of 63 patients who underwent axillary dissection of level I, I-II, or I-III lymph nodes. Then we created the modified tangential irradiation technique and applied this technique to 16 patients and checked the irradiation volume by CT scans. RESULTS We found that all of the surgical clips on lateral-view simulator films were on the ventral side of the dorsal edge line of the humeral head. All but one clip were on the caudal side of the caudal edge line of the humeral head. Accordingly, it is possible to irradiate almost all axillary lymph node regions by setting the dorsal edge of the irradiation field on lateral-view simulator films at the dorsal edge of the humeral head and the cranial edge at the caudal edge of the humeral head. CONCLUSIONS All breast tissue and the entire axillary lymph node region can be covered by the modified tangential irradiation technique without increasing the lung volume irradiated.

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.

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.

Monitoring of response to radiation therapy for human tumor xenografts using99mTc-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 of99mTc-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 and99mTc-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 in99mTc-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 the99mTc-HL91 uptake, tumor size or radiation dose. Comparing99mTc-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). Sequential99mTc-HL91 imaging of KB-31 and their autoradiography indicated that tumors whose99mTc-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 in99mTc-HL91 uptake was relatively small.Conclusion:99mTc-HL91 uptake in tumors did not always relate to their sensitivities to radiation therapy. Sequential99mTc-HL91 imagings post irradiation showed that the increase in99mTc-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 by99mTc-HL91 imaging is a good tool to predict the radiosentivities of tumors.

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.

Variation of dose distribution of stereotactic radiotherapy for small-volume lung tumors under different respiratory conditions

PURPOSE To clarify the effects of respiratory condition on dose calculation for stereotactic radiotherapy of small lung tumors. METHODS AND MATERIALS Computed tomography (CT) data were obtained for nine tumors (diameter, 2.1-3.6cm; mean, 2.7cm) during the stable state, deep expiration, and deep inspiration breath-hold states. Rotational Irradiation with 3 non-coplanar arcs (Rotational Irradiation) and static irradiation with 18 non-coplanar ports (Static Irradiation) using 6-MV photons were evaluated using Fast Fourier Transform (FFT) convolution and Multigrid (MG) superposition algorithms. Dose-volume histograms (DVHs), mean path-length (PL) and mean effective path-length (EPL) were calculated. RESULTS Although the PL was larger for the inspiration state than for the stable state and the expiration state, the EPL was 0.4-0.5cm smaller in the inspiration state than in the expiration state (p=0.01 for Rotational Irradiation; p=0.03 for Static Irradiation). The isocenter dose obtained by the FFT convolution algorithm was 7-12% higher than that obtained with the MG superposition algorithm. A leftward shift of the DVH obtained by MG superposition was noted for the inspiration state compared with the expiration state. CONCLUSIONS The choice of the proper algorithm is important to accounting for changes in respiration state. Differences in isocenter dose were not large among the respiratory states analyzed. EPL was a little shorter for inspiration than for expiration, although there were larger and reverse trends in path length. A leftward shift of the DVH obtained for the inspiration state when MG superposition was used.

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

PurposeThe 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 methodsTiny 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.ResultsLocalized 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.ConclusionSpecific 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

PurposeAs 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 methodsInterface 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.ResultsThe 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.ConclusionThree-dimensional display of DOSXYZnrc doses on a dedicated RTP system could provide all the existing facilities of the system for quantitative dose analysis.

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.

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.