Yoshiharu Negoro

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.

18F-FDG and11C-methionine PET for evaluation of treatment response of lung cancer after stereotactic radiotherapy

This study was performed to investigate the feasibility of FDG- and L-[methyl-11C]methionine (Met)-PET for the follow up of lung cancer after stereotactic radiotherapy (SRT). Nine patients (pt) with solitary lung cancer underwent SRT. Met- and FDG-PET studies were performed one week before SRT and from one week to 8 months after SRT. Responses to SRT were complete in 2 pt and partial in 7 pt. Met- and FDG-PET scan showed high tracer uptake in all tumors before SRT. After SRT, standardized uptake values (SUV) of FDG and Met changed concordantly. Both decreased with time in 5 pt but did not decrease steadily in 4 pt, where 2 pt showed an increase at 1 to 2 weeks after SRT and 2 pt showed an increase at more than 3 months after SRT. The former appears to reflect the acute reaction to SRT and the latter radiation-induced pneumonitis. Although the addition of Met-PET did not provide additional information over FDG-PET, FDG- and Met-PET could be used to evaluate the treatment effect of SRT.

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.

A randomized phase II study of cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer: Short-term infusion versus protracted infusion chemotherapy (KROSG0101/JROSG021)

PURPOSE A randomized phase II study was conducted to compare the toxicity and efficacy of combining short-term chemotherapy (CT) or protracted CT with radiotherapy (RT) for esophageal cancer. MATERIALS AND METHODS Eligible patients were <75 years and with performance status (PS) of 0-2, and had stages II-IVA esophageal cancer. Two cycles of cisplatin 70 mg/m(2) for 1 day and 5FU 700 mg/m(2) for 5 days (arm A) or cisplatin 7 mg/m(2) for 10 days and 5FU 250 mg/m(2) for 14 days (arm B) were given with RT of 60Gy/30 fractions/7 weeks (1-week split). RESULTS Of 91 patients enrolled, 46 were randomized to arm A and 45 to arm B. Two cycles of CT were given concurrently with RT for 89% in arm A and for 71% in arm B with significant difference (P=.031). The 2- and 5-year overall survival rates for arm A were 46% and 35%, while those for arm B were 44% and 24%, respectively, without significant difference. The 2- and 5-year progression-free survival rates for arm A were 30% and 30%, while those for arm B were 29% and 12%, respectively. CONCLUSIONS Protracted infusion CT with RT provides no advantage over standard short-term infusion CT with RT for esophageal cancer.

Long-term follow-up of a randomized phase II study of Cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer (KROSG0101/JROSG021)

OBJECTIVE Long-term survival and late toxicities of a randomized Phase II study of chemoradiotherapy for esophageal cancer were analyzed. METHODS Eligible patients were <75 years old and performance status 0-2, and had Stages II-IVA esophageal cancer. For arm A (short-term infusion), cisplatin 70 mg/m(2) Days 1 and 29 and 5-fluorouracil 700 mg/m(2) Days 1-5 and 29-33 were given concurrently with radiotherapy of 60 Gy/30 fr/7 weeks (1 week split). For arm B (protracted infusion), cisplatin 7 mg/m(2) Days 1-5, 8-12, 29-33 and 36-40, and 5-fluorouracil 250 mg/m(2) Days 1-14 and 29-42 were given with the same radiotherapy. Two cycles of consolidation cisplatin/5-fluorouracil chemotherapy were given to both arms. RESULTS Between 2001 and 2006, 91 patients were enrolled; 46 were randomized to arm A, and 45 to arm B. The 2- and 5-year overall survival rates for arm A were 46 and 35% (95% confidence interval: 22-48%), while those for arm B were 44 and 22% (11-35%), respectively. Excluding four patients with early death, seven (17%) patients in arm A and eight (18%) in arm B showed late toxicities of Grade 3 or more. Most of the toxicities were cardiac or pleural toxicities. Patients with severe late toxicities often had coexistent hypothyroidism. There were three patients with a secondary malignancy possibly related to treatment. CONCLUSIONS Low-dose protracted infusion chemotherapy with radiotherapy is not superior to full-dose short-term infusion chemotherapy with radiotherapy for esophageal cancer. Late toxicities, including cardiac and pleural toxicities, hypothyroidism and secondary malignancy, should be carefully monitored.

The use of a permanent magnetic resonance imaging system for radiotherapy treatment planning of bone metastases

PURPOSE To evaluate the usefulness of magnetic resonance (MR) imaging-based radiotherapy treatment planning (RTTP) for bone metastases in clinical applications. METHODS AND MATERIALS MR imaging-based RTTP was carried out for 28 patients with bone metastases using a permanent magnetic MR unit. Twenty-three patients received MR imaging-assisted X-ray simulation, and five underwent MR simulation. In MR imaging-assisted X-ray simulation, the radiation fields defined by an X-ray simulator were modified based on MR information scanned in the exact treatment position using MR skin markers. In MR simulation, both isocenter position and field size were determined on MR images and projected onto the patients skin. RESULTS All lesions unclear on other imaging modalities could be clearly identified on MR imaging. Of the 23 patients receiving MR imaging-assisted X-ray simulation, modification of the original radiation field was necessary in 14 patients (extended in 9, reduced in 4, and completely changed in 1). In MR simulation, appropriate radiation fields could be easily and quickly determined using MR imaging. CONCLUSION Methods for MR imaging-based RTTP were developed and clinically implemented for patients with bone metastases, and they were shown to be useful for improving the accuracy of the tumor location. They would provide better therapeutic/palliative benefit to particular patients with bone metastases and could also be applied to other lesions in the future.

Clinical evaluation of dynamic arc conformal radiotherapy for paraaortic lymph node metastasis

PURPOSE This study was performed to evaluate the efficacy and safety of dynamic arc conformal radiotherapy, a simple intensity modulated radiation therapy (IMRT), for the treatment of paraaortic lymph node metastases. MATERIALS AND METHODS Twenty-nine patients with paraaortic lymph node metastases were enrolled in this study. The total planned dose was 55-60 Gy. A computed tomography (CT) simulator was used in the treatment planning. RESULTS The total radiation dose delivered was 50-63.4 Gy (median 60 Gy). Sixteen of 29 patients showed local tumor shrinkage on CT, and the 2 year in-field recurrence free survival rate was 58%. Acute Grade 1 and Grade 2 gastrointestinal disorders occurred in 31% and 17%, respectively, and acute Grade 2 liver dysfunction occurred in 7%. As a late complication, Grade 1 and Grade 2 liver dysfunction occurred in six patients (21%) and five patients (17%), respectively. There was no renal dysfunction or myelopathy detected. CONCLUSION Dynamic arc conformal radiotherapy, a simple IMRT, is a safe and effective treatment method for paraaortic lymph node metastasis.

Comparison of the outcomes of stereotactic body radiotherapy and surgery in elderly patients with cT1-2N0M0 non-small cell lung cancer

BACKGROUND This study aimed to compare the outcomes of stereotactic body radiotherapy (SBRT) and surgery in elderly patients with cT1-2N0M0 non-small cell lung cancer (NSCLC). METHODS Elderly patients (≥75 years) with cT1-2 (≤5 cm) N0M0 NSCLC who were treated with SBRT (n=35) or surgery (n=183) between January 2001 and December 2011 were analyzed. RESULTS The following radiation doses were administered: 48 Gy/4-6 fractions in 12 patients; 50 Gy/4-5 fractions in 20; and 60 Gy/8 fractions in 3. The following surgical methods were performed: pneumonectomy in 2 patients, lobectomy in 154, segmentectomy in 23, and wedge resection in 4. Patients in the SBRT group had a higher mean age, a worse performance status, and a lower percentage of forced expiratory volume in 1.0 s than those in the surgery group. The overall 5-year survival rates were 43.8% and 67.6% for the SBRT and surgery groups, respectively (p=0.057, log-rank test). Regarding tumor diameter, patients in the surgery group survived significantly longer than did those in the SBRT group (>20-mm tumors, p=0.027; >30-mm tumors p=0.043), whereas survival did not differ significantly between the groups for ≤20-mm tumors (p=0.982). Multivariate analysis confirmed the improved survival in the surgery group compared to the SBRT group for all tumors (p=0.034) and for >20-mm tumors (p=0.016). CONCLUSIONS Post-therapeutic survival among elderly patients might be better with surgery than with SBRT in NSCLC patients with tumors >20 mm.

Radiotherapy combined with transcatheter arterial infusion chemotherapy for locally advanced cervical cancer

Twenty-four patients with locally advanced cervical cancer were treated with radiation therapy (RT) and transcatheter arterial infusion (TAI) chemotherapy, while 22 patients were treated with RT alone. RT consisted of a combination of external irradiation and high-dose-rate intracavitary brachytherapy. TAI therapy consisted of two sessions using cisplatin and pirarubicin, performed concurrently during the periods of external irradiation. The local-regional control rates at 1 year for the patients treated with RT plus TAI and for those treated with RT alone were 87.5% and 58.3%, respectively (p < 0.05). The 3-year cause-specific survival (CSS) rates for RT plus TAI, and RT alone were 67.1% and 55.9%, respectively (p = n.s.). The 3-year CSS rate for the 14 patients treated with RT and TAI who had well- or moderately differentiated squamous cell carcinoma without pelvic lymph node swelling was 100%, while that for the 19 patients with the same background treated with RT alone was 49% (p < 0.01). Radiation therapy combined with TAI appears to be an effective and safe treatment modality for patients with locally advanced cervical cancer.