Seiko Hashimoto

Physical aspects of a real-time tumor-tracking system for gated radiotherapy

PURPOSE To reduce uncertainty due to setup error and organ motion during radiotherapy of tumors in or near the lung, by means of real-time tumor tracking and gating of a linear accelerator. METHODS AND MATERIALS The real-time tumor-tracking system consists of four sets of diagnostic X-ray television systems (two of which offer an unobstructed view of the patient at any time), an image processor unit, a gating control unit, and an image display unit. The system recognizes the position of a 2.0-mm gold marker in the human body 30 times per second using two X-ray television systems. The marker is inserted in or near the tumor using image guided implantation. The linear accelerator is gated to irradiate the tumor only when the marker is within a given tolerance from its planned coordinates relative to the isocenter. The accuracy of the system and the additional dose due to the diagnostic X-ray were examined in a phantom, and the geometric performance of the system was evaluated in 4 patients. RESULTS The phantom experiment demonstrated that the geometric accuracy of the tumor-tracking system is better than 1.5 mm for moving targets up to a speed of 40 mm/s. The dose due to the diagnostic X-ray monitoring ranged from 0.01% to 1% of the target dose for a 2.0-Gy irradiation of a chest phantom. In 4 patients with lung cancer, the range of the coordinates of the tumor marker during irradiation was 2.5-5.3 mm, which would have been 9.6-38.4 mm without tracking. CONCLUSION We successfully implemented and applied a tumor-tracking and gating system. The system significantly improves the accuracy of irradiation of targets in motion at the expense of an acceptable amount of diagnostic X-ray exposure.

Image fusion between 18FDG-PET and MRI/CT for radiotherapy planning of oropharyngeal and nasopharyngeal carcinomas

PURPOSE Accurate diagnosis of tumor extent is important in three-dimensional conformal radiotherapy. This study reports the use of image fusion between (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG-PET) and magnetic resonance imaging/computed tomography (MRI/CT) for better targets delineation in radiotherapy planning of head-and-neck cancers. METHODS AND MATERIALS The subjects consisted of 12 patients with oropharyngeal carcinoma and 9 patients with nasopharyngeal carcinoma (NPC) who were treated with radical radiotherapy between July 1999 and February 2001. Image fusion between 18FDG-PET and MRI/CT was performed using an automatic multimodality image registration algorithm, which used the brain as an internal reference for registration. Gross tumor volume (GTV) was determined based on clinical examination and 18FDG uptake on the fusion images. Clinical target volume (CTV) was determined following the usual pattern of lymph node spread for each disease entity along with the clinical presentation of each patient. RESULTS Except for 3 cases with superficial tumors, all the other primary tumors were detected by 18FDG-PET. The GTV volumes for primary tumors were not changed by image fusion in 19 cases (89%), increased by 49% in one NPC, and decreased by 45% in another NPC. Normal tissue sparing was more easily performed based on clearer GTV and CTV determination on the fusion images. In particular, parotid sparing became possible in 15 patients (71%) whose upper neck areas near the parotid glands were tumor-free by 18FDG-PET. Within a mean follow-up period of 18 months, no recurrence occurred in the areas defined as CTV, which was treated prophylactically, except for 1 patient who experienced nodal recurrence in the CTV and simultaneous primary site recurrence. CONCLUSION This preliminary study showed that image fusion between 18FDG-PET and MRI/CT was useful in GTV and CTV determination in conformal RT, thus sparing normal tissues.

The suppression of metastases and the change in host immune response after low-dose total-body irradiation in tumor-bearing rats.

We have shown that metastasis is suppressed by low-dose total-body irradiation (TBI) in tumor-bearing rats. We have evaluated the immunological effects of low-dose TBI. Total-body irradiation with 0.2 Gy was given 14 days after the implantation of 5 x 10(5) allogenic hepatoma cells (KDH-8) which produce transforming growth factor beta (TGF-beta). On day 21, the splenocytes and tumor-tissue infiltrating lymphocytes were analyzed by FACScan and RT-PCR for the mRNA of the genes that encode tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), TGF-beta, interleukin (IL)-4, IL-10 and IL-6. The same procedure was conducted with untreated rats and with rats that underwent local irradiation with 0.2 Gy. The low-dose TBI significantly decreased the incidence of lung and lymph node metastasis (P < 0.01), whereas the same dose of local irradiation had no effect on the incidence of metastasis. The proportion of CD8+ cells in splenocytes increased in the low-dose TBI group (P < 0.01) compared to the locally irradiated and the untreated groups. The tumor-tissue infiltrating lymphocytes were also significantly increased after low-dose TBI (P < 0.01). The FACScan analysis revealed that 72% of the tumor-tissue infiltrating lymphocytes were CD8+. In both spleen and tumor tissue after low-dose TBI, mRNA expression of the genes that encode IFN-gamma and TNF-alpha increased, while that of the Tgfb gene decreased. There was no expression of the mRNAs of the Il4, Il6 and Il10 genes. CD8+ cells and the cytokine network may play an important role in the antitumor effect of low-dose TBI.

Three-dimensional movement of a liver tumor detected by high-speed magnetic resonance imaging

OBJECTIVE Three-dimensional (3D) movement of a spherical liver tumor during respiration was investigated with magnetic resonance imaging (MRI) using a high-speed sequence. METHODS A marker was placed on the surface of the patient as a reference of distance. Repetition time (TR) was 7.7 ms, echo time (TE) was 4.2 ms, flip angle was 20 degrees, section thickness was 8 mm, and a 256 x 128 matrix was used. The acquisition time was 1.0 s followed by an interval of 0.5 s. The 20 tumor contours extracted during 30 s were superimposed on sagittal and coronal MR images. RESULTS The maximum value of tumor edge location was 3.9 cm in the cranio-caudal direction, 2.3 cm in the ventro-dorsal direction, and 3.1 cm in the lateral direction. The mean length of tumor displacement observed was 2.1 cm in the cranio-caudal direction, 0.8 cm in the ventro-dorsal and 0.9 cm in the left-right direction, respectively. The locus of the center of the tumor contour in the sagittal cross section was inclined at 23 degrees and in the coronal cross section was inclined at 18 degrees to the cranio-caudal axis of body. CONCLUSION In conclusion, 3D movement of a spherical liver tumor was detected using rapid MRI sequential examinations. Magnetic resonance imaging has a potential to improve the accuracy of the planning target volume of a liver tumor.

Magnetic resonance imaging system for three-dimensional conformal radiotherapy and its impact on gross tumor volume delineation of central nervous system tumors.

PURPOSE We developed an MRI system for three-dimensional planning in radiotherapy. Its contribution on gross tumor volume (GTV) delineation of central nervous system (CNS) diseases was evaluated. METHODS AND MATERIALS The MRI system, with corrected distortion, was registered on computed tomography (CT) by means of fiducial/anatomic landmarks. In 41 consecutive patients with various CNS diseases, GTVs determined by MRI/CT registration (MR/CT-GTV) and CT alone (CT-GTV) were compared. Hard copies of diagnostic MRI were shown to doctors when CT-GTV was determined to simulate a conventional planning situation. Multi-observer volumetric analysis was conducted, assessing interobserver deviations among four radiation oncologists and intermethodological deviations between MR/CT-GTV and CT-GTV. RESULTS Overall, the mean of geometric distortion was significantly reduced from 1.08 mm to 0.3 mm by distortion correction (p < 0.0001). The contribution of the correction was apparent at >12.0 cm radius from the center of the magnetic field. Interobserver deviation was significantly reduced by MR/CT registration (p = 0.005). The improvement was significant for acoustic neurinoma (p = 0.038), astrocytomas (p = 0.043), and lesions at the cerebellum/brainstem (p = 0.008). The regression coefficient between MR/CT-GTV and CT-GTV was <0.9 for cerebellum/brainstem lesions, suggesting that MRI/CT-GTV was smaller than CT-GTV. CONCLUSIONS This system is feasible for three-dimensional planning and was shown to reduce interobserver deviations in GTV delineation for CNS diseases.

High-speed magnetic resonance imaging for four-dimensional treatment planning of conformal radiotherapy of moving body tumors.

PURPOSE High-speed magnetic resonance imaging (MRI) was applied to the determination of the planning target volume (PTV) of moving hepatobiliary tumors. METHODS AND MATERIALS Three moving tumors, including two metastatic hepatic tumors and one bile duct tumor, were examined using high-speed MRI and reference fiducial markers before external radiotherapy. Patients were examined for 30 seconds under conditions of normal breathing during the examination. The coordinates of the center of the tumor contours were shown on sagittal and coronal images displayed on the monitor. RESULTS The maximum length of movement was 10.6 +/- 7.0 mm in a craniocaudal direction; 5.2 +/- 1.8 mm in a lateral direction; and 4.6 +/- 1.6 mm in a ventrodorsal direction. When the PTV was determined using MRI at exhalation phase with a 10-mm safety margin, clinical target volume (CTV) was not covered in 19% of all images in the 3 patients. With MRI at inhalation phase with a 10-mm safety margin, CTV was not covered in 36% of all images. CONCLUSION Four-dimensional treatment planning using high speed MRI, and integrating time and spatial information, has the potential to determine the planning target volume of moving body tumors more precisely than does conventional CT planning.

Role of radiotherapy for mucoepidermoid carcinoma of salivary gland.

This report analyzes 61 patients with mucoepidermoid carcinomas of the salivary gland treated by surgery alone or by surgery plus radiotherapy. Local control for all 61 patients at 5 and 10 years was achieved for 88.8 and 79.7% of the cases. Although the rate of positive surgical margin was higher in patients treated with surgery and radiotherapy (radiotherapy group) than in patients treated by surgery alone (surgery group), the local control rates of the two groups showed no statistically significant differences. There was no local recurrence in seven patients receiving post-operative radiotherapy above 55 Gy while there were three local relapses among 17 patients receiving 55 Gy or lower doses (P < 0.05). The 5- and 10-year actual survival rates were 73.4 and 63.3% respectively. Histopathologic subtype of mucoepidermoid carcinomas correlated with regional lymph node involvement and survival. There were no differences in the local control and survival rates of patients with major salivary gland tumors and patients with minor salivary gland tumors. Radiotherapy using 55 Gy or more combined with operation achieved local control and survival rates comparable with complete resection of tumors even if a positive surgical margin was more frequent in the radiotherapy groups.

The role of radiotherapy in treating squamous cell carcinoma of the external auditory canal, especially in early stages of disease

PURPOSE Our intent was to investigate the role of radiotherapy in treating external auditory canal squamous cell carcinoma, especially in early stages of disease. MATERIALS AND METHODS The treatment results for 20 patients treated between 1980 and 1998 were retrospectively analyzed. Radiotherapy was used as an initial treatment without surgery in eight patients and with surgery in 12 patients. The patients treated by radiotherapy alone received 65 Gy in 26 fractions over 6.5 weeks. The patients treated with radiotherapy perioperatively received 30-75 Gy in 12-30 fractions. The follow-up period for survivors including patients died of intercurrent disease ranged from 7 to 205 months (mean: 71 months). RESULTS The 5-year survival rate calculated by the Kaplan-Meier method for all patients was 59%. According to Stell classification (Laryncol. Otol. 99 (1985) 847), the 5-year survival rates for eight patients with T1 disease and eight with T2 disease were 100 and 38%, respectively. In the eight patients with T1 disease, disease control was 100%. Local control with hearing preservation was achieved in five patients with T1 disease by radiotherapy alone. No late complications related to radiotherapy were observed. CONCLUSIONS A precise diagnosis of the disease in terms of whether or not it has invaded the bone is important in order to predict the treatment outcome. Radiotherapy with or without surgery is the treatment of choice for patients with T1-stage disease. Surgery with radiotherapy is recommended as standard care for tumors with bony invasion.

Ipsilateral irradiation for carcinomas of tonsillar region and soft palate based on computed tomographic simulation.

PURPOSE To reduce xerostomia in selected patients with carcinomas of the tonsillar region and soft palate. METHODS AND MATERIALS We evaluated the treatment results of 32 patients with tonsillar region and soft palate carcinoma treated by radical radiotherapy between May 1989 and December 1996. They have a unilateral tumor that did not cross midline and have no contralateral neck lymphnode metastasis and treated with an ipsilateral technique (an anterior oblique and a posterior oblique field). All patients were planned with computed tomographic (CT) simulation and given 65 Gy in 26 fractions in 6.5 weeks with or without 5-15 Gy boost irradiation. The median follow-up was 44 months (4-86 months). RESULTS Five-year overall, cause-specific survival, local control, and regional control rate was 64, 79, 74 and 81%. No failure at the contralateral neck occurred. Moderate or severe symptomatic xerostomia was seen in 3 (9%) patients and ostero-radionecrosis requiring surgery occurred in one (3.3%) of 32 patients. CONCLUSION It is suggested that the ipsilateral technique is indicated in patients who had an unilateral tonsillar region or soft palate carcinoma that did not cross midline and have no contralateral neck lymphnode metastasis.

Skull-base invasion of nasopharyngeal carcinoma : Magnetic resonance imaging findings and therapeutic implications

PURPOSE To evaluate the value of skull-base abnormality on MRI for predicting local recurrence in nasopharyngeal carcinoma. MATERIALS AND METHODS Between November 1988 and February 1997, 48 patients with NPC were examined with both MRI (1.5 T) and CT prior to radiation therapy. T classification (1987 UICC) based on physical examination and CT findings were T1 in 3 cases, T2 in 22, T3 in 9, and T4 in 14. On MRI, low-intensity tissue with Gd enhancement in the marrow of the skull was considered to be a suspicious finding of skull-base invasion. CT simulation was performed in all patients. The total dose to the primary tumor was 60-75 Gy (mean, 67 Gy). The mean follow-up period was 42 months. RESULTS All 14 T4 patients had abnormal tissue in the marrow of the skull base on MRI. Thirty-eight percent (13 of 34) of T1-3 patients were suspected to have skull-base invasion based on MRI (0% for T1, 27% [6 of 22] for T2, and 78% [7 of 9] for T3). The 5-year local control rate was significantly different between T1-3 and T4 tumors (97% vs. 69%, p < 0.025) but was not different by the presence of the MRI abnormality in the skull base. CONCLUSION Skull-base invasion suspected solely by MRI does not relate to local recurrence provided that careful treatment planning is performed with the aid of MRI and CT simulator.