Masaki Kokubo

Stereotactic hypofractionated high-dose irradiation for Stage I nonsmall cell lung carcinoma: Clinical outcomes in 245 subjects in a Japanese Multiinstitutional Study

Stereotactic irradiation (STI) has been actively performed using various methods to achieve better local control of Stage I nonsmall cell lung carcinoma (NSCLC) in Japan. The authors retrospectively evaluated results from a Japanese multiinstitutional study.

Hypofractionated Stereotactic Radiotherapy (HypoFXSRT) for Stage I Non-small Cell Lung Cancer: Updated Results of 257 Patients in a Japanese Multi-institutional Study

Introduction: Hypofractionated stereotactic radiotherapy (HypoFXSRT) has recently been used for the treatment of small lung tumors. We retrospectively analyzed the treatment outcome of HypoFXSRT for stage I non-small cell lung cancer (NSCLC) treated in a Japanese multi-institutional study. Methods: This is a retrospective study to review 257 patients with stage I NSCLC (median age, 74 years: 164 T1N0M0, 93 T2N0M0) were treated with HypoFXSRT alone at 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. A total dose of 18 to 75 Gy at the isocenter was administered in one to 22 fractions. The median calculated biological effective dose (BED) was 111 Gy (range, 57–180 Gy) based on α/β = 10. Results: During follow-up (median, 38 months), pulmonary complications of above grade 2 arose in 14 patients (5.4%). Local progression occurred in 36 patients (14.0%), and the local recurrence rate was 8.4% for a BED of 100 Gy or more compared with 42.9% for less than 100 Gy (p < 0.001). The 5-year overall survival rate of medically operable patients was 70.8% among those treated with a BED of 100 Gy or more compared with 30.2% among those treated with less than 100 Gy (p < 0.05). Conclusions: Although this is a retrospective study, HypoFXSRT with a BED of less than 180 Gy was almost safe for stage I NSCLC, and the local control and overall survival rates in 5 years with a BED of 100 Gy or more were superior to the reported results for conventional radiotherapy. For all treatment methods and schedules, the local control and survival rates were better with a BED of 100 Gy or more compared with less than 100 Gy. HypoFXSRT is feasible for curative treatment of patients with stage I NSCLC.

Clinical outcomes of 3D conformal hypofractionated single high-dose radiotherapy for one or two lung tumors using a stereotactic body frame

PURPOSE This study was performed to evaluate the clinical outcomes of three-dimensional (3D) conformal hypofractionated single high-dose radiotherapy for one or two lung tumors using a stereotactic body frame. MATERIALS AND METHODS Forty patients who were treated between July 1998 and November 2000 and were followed for >10 months were included in this study. Of the 40 patients, 31 had primary lung cancer and 9 had metastatic lung cancer. The primary lung cancer was staged as T1N0M0, T2N0M0, and T3N0M0 in 19, 8, and 4 patients, respectively. The primary sites of metastatic lung cancer were the colon in 4, tongue in 2, and osteosarcoma, lung cancer, and hepatocellular carcinoma in 1 each. 3D treatment planning was performed to maintain the target dose homogeneity within 15% and to decrease the irradiated lung volume from >20 Gy to <25%. All patients were irradiated using a stereotactic body frame and received 4 times 10-12 Gy single high-dose radiation at the isocenter during a period of 5-13 days (median 12). RESULTS The initial 3 patients received 40, and the remaining 37 patients received 48 Gy after dose escalation. Of the 33 tumors followed >6 months, 6 tumors (18%) disappeared completely after treatment. Twenty-five tumors (76%) decreased in size by 30% or more after treatment. Therefore, 31 tumors (94%) showed a local response. During the follow-up of 4-37 months (median 19), no pulmonary complications greater than National Cancer Institute-Common Toxicity Criteria Grade 2 were noted. Of the 16 patients with histologically confirmed T1N0M0 primary lung cancer who received 48 Gy, all tumors were locally controlled during the follow-up of 6-36 months (median = 19). In 9 tumors with lung metastases that were irradiated with 48 Gy in total, 2 tumors did not show a local response. Finally, 3 tumors (33%) with lung metastases relapsed locally at 6-12 months (median 7) after treatment during the follow-up of 3-29 months (median 18). CONCLUSION 3D conformal hypofractionated single high-dose radiotherapy of 48 Gy in 4 fractions using a stereotactic body frame was useful for the treatment of lung tumors.

The effectiveness of an immobilization device in conformal radiotherapy for lung tumor: reduction of respiratory tumor movement and evaluation of the daily setup accuracy.

PURPOSE To evaluate the daily setup accuracy and the reduction of respiratory tumor movement using a body frame in conformal therapy for solitary lung tumor. METHODS AND MATERIALS Eighteen patients with a solitary lung tumor underwent conformal therapy using a body frame. The body shell of the frame was shaped to the patients body contour. The respiratory tumor movement was estimated using fluoroscopy, and if it was greater than 5 mm, pressure was applied to the patients abdomen with the goal of minimizing tumor movement. CT images were then obtained, and a treatment planning was made. A total dose of 40 or 48 Gy was delivered in 4 fractions. Portal films were obtained at each treatment, and the field displacements between them and the simulation films were measured for daily setup errors. The patients were repositioned if the setup error was greater than 3 mm. Correlations were analyzed between patient characteristics and the tumor movement, or the tumor movement reduction and the daily setup errors. RESULTS Respiratory tumor movement ranged from 0 to 20 mm (mean 7.7 mm). The abdominal press reduced the tumor movement significantly from a range of 8 to 20 mm to a range of 2 to 11 mm (p = 0.0002). Daily setup errors were within 5 mm in 90%, 100%, and 93% of all verifications in left-right, anterior-posterior, and cranio-caudal directions, respectively. Patient repositioning was performed in 25% of all treatments. No significant correlation was detected between patient characteristics and tumor movement, tumor movement reduction, and the daily setup errors. CONCLUSIONS The abdominal press was successful in reducing the respiratory tumor movement. Daily setup accuracy using the body frame was acceptable. Verification should be performed at each treatment in hypofractionated conformal therapy.

External and intraoperative radiotherapy for resectable and unresectable pancreatic cancer: Analysis of survival rates and complications

PURPOSE Clinical results of intraoperative radiotherapy (IORT) and/or external beam radiotherapy (EBRT) for both resectable and unresectable pancreatic cancer were analyzed. METHODS AND MATERIALS Between 1980 and 1995, 332 patients with pancreatic cancer were treated with surgery and/or radiation therapy (RT). Of the 332 patients, 157 patients were treated with surgical resection of pancreatic tumor, and the remaining 175 patients had unresectable pancreatic tumors. Among the 157 patients with resected pancreatic cancer, 62 patients were not treated with RT, while 40 patients were treated with EBRT alone (mean RT dose; 46.3 Gy) and 55 patients with IORT (25.2 Gy) +/- EBRT (44.0 Gy). On the other hand, among the 175 patients with unresectable pancreatic cancer, 58 patients were not treated with RT, 46 patients were treated with EBRT alone (39.2 Gy), and the remaining 71 patients with IORT (29.3 Gy) +/- EBRT (41.2 Gy). RESULTS For 87 patients with curative resection, the median survival times (MSTs) of the no-RT, the EBRT, and the IORT +/- EBRT groups were 10.4, 13.0, and 15.5 months, respectively, without significant difference. For 70 patients with noncurative resection, the MSTs of the no-RT, the EBRT, and the IORT +/- EBRT groups were 5.3, 8.7, and 6.5 months, respectively. When the EBRT and the IORT +/- EBRT groups were combined, the survival rate was significantly higher than that of the no RT group for noncuratively resected pancreatic cancers (log rank test; p = 0.028). The 2-year survival probability of the IORT +/- EBRT group (16%) was higher than that of the EBRT group (0%). For unresectable pancreatic cancer, the MSTs of 52 patients without distant metastases were 6.7 months for palliative surgery alone, 7.6 months for EBRT alone, and 8.2 months for IORT +/- EBRT. The survival curve of the IORT +/- EBRT group was significantly better than that of the no-RT group (p < 0.05), and the difference between the IORT +/- EBRT and the EBRT alone groups was marginally significant (p = 0.056). In addition, the 2-year survival probability for the IORT +/- EBRT group was 14%, while no 2-year survival was observed in the no RT or the EBRT groups. Multivariate analysis using the Cox proportional hazards model revealed that tumor size, stage (Stages 1, 2 vs. Stages 3, 4), and curability of resection were significant variables for resectable pancreatic cancer, while distant metastases and performance of IORT were significant variables for unresectable pancreatic cancer. The dose of EBRT was a marginally significant factor for both resectable and unresectable tumors (both p = 0.06). In terms of complications, ulcers of gastrointestinal tract were noted in 14% of the 126 patients treated with IORT. CONCLUSION Although prolongation of the MST by IORT was not remarkable, long survivals (>2 years) were obtained by IORT +/- EBRT for noncuratively resected and unresectable pancreatic cancer. IORT combined with EBRT is indicated for noncurative resected or unresectable pancreatic cancer without distant metastases.

Initial validations for pursuing irradiation using a gimbals tracking system

Our newly designed image-guided radiotherapy (IGRT) system enables the dynamic tracking irradiation with a gimbaled X-ray head and a dual on-board kilovolt imaging subsystem for real-time target localization. Examinations using a computer-controlled three-dimensionally movable phantom demonstrated that our gimbals tracking system significantly reduced motion blurring effects in the dose distribution compared to the non-tracking state.

Surgical Treatment of Local Recurrence After Stereotactic Body Radiotherapy for Primary and Metastatic Lung Cancers

Introduction: Stereotactic body radiotherapy (SBRT) has been proposed as an alternative to surgery for the treatment of lung cancer. The treatment of local recurrence that occurs after SBRT has not been reported. We present surgical outcomes for local recurrence following SBRT for primary and metastatic lung cancers. Methods: Seven of the patients who received SBRT between 2002 and 2008 underwent salvage surgery for local recurrence. These seven patients (two with stage I non-small cell lung cancer and five with metastatic tumors) were operable, although they refused surgery and chose SBRT for the first treatment as a less invasive procedure. Results: Six of the seven patients underwent lobectomy, and the other patient underwent segmentectomy. None of the seven patients had direct pleural adhesion resulting from SBRT, although, in general, radiation fibrosis occurs after radiotherapy and induces pleural adhesion that makes surgery difficult. Conclusions: Our study suggests that SBRT may not be the cause of difficulties encountered during the surgical process, and surgery is a good alternative treatment for local recurrence after SBRT. During follow-up after SBRT, the appearance of tumor regrowth on lung images resembled that of inflammatory changes such as radiation pneumonitis. We suggest that close follow-ups should be mandatory after SBRT.

Incidence of Brain Atrophy and Decline in Mini-Mental State Examination Score After Whole-Brain Radiotherapy in Patients With Brain Metastases: A Prospective Study

PURPOSE To determine the incidence of brain atrophy and dementia after whole-brain radiotherapy (WBRT) in patients with brain metastases not undergoing surgery. METHODS AND MATERIALS Eligible patients underwent WBRT to 40 Gy in 20 fractions with or without a 10-Gy boost. Brain magnetic resonance imaging or computed tomography and Mini-Mental State Examination (MMSE) were performed before and soon after radiotherapy, every 3 months for 18 months, and every 6 months thereafter. Brain atrophy was evaluated by change in cerebrospinal fluid-cranial ratio (CCR), and the atrophy index was defined as postradiation CCR divided by preradiation CCR. RESULTS Of 101 patients (median age, 62 years) entering the study, 92 completed WBRT, and 45, 25, and 10 patients were assessable at 6, 12, and 18 months, respectively. Mean atrophy index was 1.24 +/- 0.39 (SD) at 6 months and 1.32 +/- 0.40 at 12 months, and 18% and 28% of the patients had an increase in the atrophy index by 30% or greater, respectively. No apparent decrease in mean MMSE score was observed after WBRT. Individually, MMSE scores decreased by four or more points in 11% at 6 months, 12% at 12 months, and 0% at 18 months. However, about half the decrease in MMSE scores was associated with a decrease in performance status caused by systemic disease progression. CONCLUSIONS Brain atrophy developed in up to 30% of patients, but it was not necessarily accompanied by MMSE score decrease. Dementia after WBRT unaccompanied by tumor recurrence was infrequent.

Development of an ultrasmall C-band linear accelerator guide for a four-dimensional image-guided radiotherapy system with a gimbaled x-ray head.

We are developing a four-dimensional image-guided radiotherapy system with a gimbaled x-ray head. It is capable of pursuing irradiation and delivering irradiation precisely with the help of an agile moving x-ray head on the gimbals. Requirements for the accelerator guide were established, system design was developed, and detailed design was conducted. An accelerator guide was manufactured and basic beam performance and leakage radiation from the accelerator guide were evaluated at a low pulse repetition rate. The accelerator guide including the electron gun is 38 cm long and weighs about 10 kg. The length of the accelerating structure is 24.4 cm. The accelerating structure is a standing wave type and is composed of the axial-coupled injector section and the side-coupled acceleration cavity section. The injector section is composed of one prebuncher cavity, one buncher cavity, one side-coupled half cavity, and two axial coupling cavities. The acceleration cavity section is composed of eight side-coupled nose reentrant cavities and eight coupling cavities. The electron gun is a diode-type gun with a cerium hexaboride (CeB6) direct heating cathode. The accelerator guide can be operated without any magnetic focusing device. Output beam current was 75 mA with a transmission efficiency of 58%, and the average energy was 5.24 MeV. Beam energy was distributed from 4.95 to 5.6 MeV. The beam profile, measured 88 mm from the beam output hole on the axis of the accelerator guide, was 0.7 mm X 0.9 mm full width at half maximum (FWHM) width. The beam loading line was 5.925 (MeV)-Ib (mA) X 0.00808 (MeV/mA), where Ib is output beam current. The maximum radiation leakage of the accelerator guide at 100 cm from the axis of the accelerator guide was calculated as 0.33 cGy/min at the rated x-ray output of 500 cGy/min from the measured value. This leakage requires no radiation shielding for the accelerator guide itself per IEC 60601-2-1.

Reproducibility of geometric distortion in magnetic resonance imaging based on phantom studies

BACKGROUND AND PURPOSE Image distortion is one of the major drawbacks of magnetic resonance (MR) imaging for use in radiotherapy treatment planning (RTTP). In this study, the reproducibility of MR imaging distortion was evaluated by repeated phantom measurements. MATERIALS AND METHODS A grid-pattern acrylic phantom was scanned with a 0.2-Tesla permanent magnetic unit. We repeated a series of scans three times to evaluate the reproducibility of the distortion. In each series, co-ordinates at 432 intersections of the grid were measured for both T1- and T2-weighted spin-echo (SE) pulse sequences. Positional displacements and their variations at the intersections were calculated. RESULTS Averages of the displacements were distributed between 1.58 and 1.74 mm, and maximum values (MAX) between 12.6 and 15.0 mm. Within 120 mm of the image center, the average values ranged from 0.73 to 0.80 mm, and from 3.4 to 5.0 mm for MAX. The absolute values of the positional variations among three series were distributed between 0.41 and 0.88 mm for average values, and between 1.4 and 4.5 mm for MAX. CONCLUSIONS The positional variations were mostly within 3 pixels, and most of the positional displacements within the radius of 120 mm of the image center were 2 mm or less. Therefore, it will be possible to use this MR system in RTTP under limited situations, although careful applications are required for RTTP of the body. The development of a computer program to correct image distortion is expected.