Yoshiharu Negoro

Kyoto University, Kyoto, Kyoto-fu, Japan

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Publications (15)46.3 Total impact

  • Article: Long-term follow-up of a randomized Phase II study of cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer (KROSG0101/JROSG021).
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    ABSTRACT: Long-term survival and late toxicities of a randomized Phase II study of chemoradiotherapy for esophageal cancer were analyzed. 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. 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. 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.
    Japanese Journal of Clinical Oncology 07/2012; 42(9):807-12. · 1.78 Impact Factor
  • Article: Clinical practice and outcome of radiotherapy for esophageal cancer between 1999 and 2003: the Japanese Radiation Oncology Study Group (JROSG) Survey.
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    ABSTRACT: To determine the clinical results of radiotherapy (RT) for esophageal cancer in Japan. A questionnaire-based survey was conducted for esophageal cancer treated by definitive RT between 1999 and 2003. Clinical results of definitive RT for patients were collected from 9 major institutions. Only patients with good performance status (PS 0-2) who received a total dose of 50 Gy or more were included. Patients were classified into three groups: (A) stage I, (B) resectable stages II-III, (C) unresectable stages III-IVA. For group A, all patients treated by RT alone or chemo-radiotherapy (CRT) were included. For groups B and C, only those treated by CRT were included. In total, 167 patients were included in group A, 239 in group B, and 244 in group C. Approximately half of the patients in group A were treated by CRT. The median total RT dose ranged from 60 to 66 Gy. The median and range of the 5-year overall survival rates were 56% (48-83%) for group A, 29% (12-52%) for group B, and 19% (0-31%) for group C, respectively. A wide disparity in overall survival rates was noted among the institutions. A significant correlation between the number of patients treated per year and the 5-year overall survival rate was noted for groups B and C (both p < 0.05). Although the overall survival rates for stage I esophageal cancer were excellent, a significant disparity in survival rates was noted among the institutions for stage II-IVA tumors treated by CRT.
    International Journal of Clinical Oncology 05/2011; 17(1):48-54. · 1.41 Impact Factor
  • Article: Impact of double-balloon rectal catheter use in external-beam radiotherapy for prostate cancer.
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    ABSTRACT: Prostate motion and rectal sparing are important treatment strategy issues in external-beam radiotherapy for localized prostate cancer. To address these issues, we prospectively investigated the feasibility of using a double-balloon rectal catheter. The rectal catheter has inner and outer balloons that wedge the anus between them. Computed tomography (CT) examinations with and without the catheter were conducted in seven patients with localized prostate cancer treated by external-beam radiotherapy. The rectal wall sparing effect was evaluated using virtual three-dimensional conformal radiotherapy plans in each arm. To evaluate interfractional prostate motion, each patient underwent a series of four CT examinations consisting of a planning CT followed by three additional series of CT with and without a catheter during the course of radiotherapy. Virtual plans demonstrated the reduction of the dose to the rectum by expanding the posterior wall to lie outside the high- to intermediate-dose area when a catheter was applied. Interfractional prostate motion in the anteroposterior direction was effectively reduced by catheter usage; the mean ± standard deviation (SD) of the displacement was 1.3 ± 0.9 mm with a catheter as compared to 2.8 ± 1.8 mm without a catheter (P = 0.014), and the maximum displacement was successfully suppressed to 3 mm with a catheter compared to 6 mm without a catheter. Systematic and random components were also reduced with the catheter. These results suggest the feasibility and clinical applicability of the double-balloon rectal catheter.
    International Journal of Clinical Oncology 10/2010; 16(1):50-6. · 1.41 Impact Factor
  • Article: Intraoperative radiotherapy for resected pancreatic cancer: a multi-institutional retrospective analysis of 210 patients.
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    ABSTRACT: To retrospectively analyze the results of intraoperative radiotherapy (IORT) with or without external beam radiotherapy (EBRT) for resected pancreatic cancer. The records of 210 patients treated with gross complete resection (R0: 147 patients; R1: 63 patients) and IORT with or without EBRT were reviewed. One hundred forty-seven patients (70.0%) were treated without EBRT and 114 patients (54.3%) were treated in conjunction with chemotherapy. The median doses of IORT and EBRT were 25 Gy (range, 20-30 Gy) and 45 Gy (range, 20-60Gy), respectively. The median follow-up of the surviving 62 patients was 26.3 months (range, 2.7-90.5 months). At the time of this analysis, 150 of 210 patients (71.4%) had disease recurrences. Local failure was observed in 31 patients (14.8%), and the 2-year local control rate in all patients was 83.7%. The median survival time and the 2-year actuarial overall survival (OS) in all 210 patients were 19.1 months and 42.1%, respectively. Patients treated with IORT and chemotherapy had a significantly more favorable OS than those treated with IORT alone (p = 0.0011). On univariate analysis, chemotherapy use, degree of resection, carbohydrate antigen 19-9, and pathological N stage had a significant impact on OS and on multivariate analysis; these four factors were significant prognostic factors. Late gastrointestinal morbidity of NCI-CTC Grade 4 was observed in 7 patients (3.3%). IORT yields an excellent local control rate for resected pancreatic cancer with few frequencies of severe late toxicity, and IORT combined with chemotherapy confers a survival benefit compared with that of IORT alone.
    International journal of radiation oncology, biology, physics 03/2010; 77(3):734-42. · 4.59 Impact Factor
  • Article: A randomized phase II study of cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer: Short-term infusion versus protracted infusion chemotherapy (KROSG0101/JROSG021).
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    ABSTRACT: 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. 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). 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. Protracted infusion CT with RT provides no advantage over standard short-term infusion CT with RT for esophageal cancer.
    Radiotherapy and Oncology 01/2009; 92(2):260-5. · 5.58 Impact Factor
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    Article: Patterns of care study of breast-conserving therapy in Japan: comparison of the treatment process between 1995 1997 and 1999 2001 surveys.
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    ABSTRACT: The Japan Patterns of Care Study (JPCS) conducted two national surveys to identify changes associated with the treatment process of care for patients undergoing breast-conserving therapy (BCT). Between the two national surveys, the Japanese Breast Cancer Society published its treatment guideline for BCT. The first survey collected data on 865 patients treated between 1995 and 1997 (JPCS-1), and the second on 746 patients treated between1999 and 2001 (JPCS-2) by extramural audits. There was a shift to an older age distribution in JPCS-2 compared with JPCS-1. In JPCS-2, the average patient age was 53.9 compared with 51.5 in JPCS-1 (P < 0.001). There was a reduction in the extent of breast surgery and the proportion of the patients who received quadrantectomy was 57.0% in JPCS-1 and 30.3% in JPCS-2 (P < 0.001). In JPCS-2, a cast or shell for immobilization was used at a significantly higher rate of 52.9% compared with 32.6% for JPCS-1 (P < 0.001). The rate of boost irradiation was increased in JPCS-2, especially for patients with a positive surgical margin; it was significantly increased to 83.5% in JPCS-2 compared with 53.9% in JPCS-1 (P < 0.001). The second survey revealed a rapid change in the trend of the treatment of BCT in Japan and represented high compliance of the treatment guideline for BCT published by the Japanese Breast Cancer Society (JBCS) in 1999.
    Japanese Journal of Clinical Oncology 11/2007; 37(10):737-43. · 1.78 Impact Factor
  • Article: Results of radiation therapy combined with neoadjuvant hormonal therapy for stage III prostate cancer: comparison of two different definitions of PSA failure.
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    ABSTRACT: We herein report the clinical outcome of radical radiation therapy combined with neoadjuvant hormonal therapy (NHT) for stage III (International Union Against Cancer [UICC] 1997: UICC 97) prostate cancer. Prostate-specific antigen (PSA) failure-free survival was assessed according to two different definitions, and the appropriateness of each definition is discussed. Between October 1997 and December 2000, 27 patients with stage III prostate cancer were enrolled in this study. The median pretreatment PSA level was 29 ng/ml (range, 7.4-430 ng/ml). The Gleason score (GS) was 7 or more in 22 patients (81%). All patients received 3 months of NHT with a luteinizing hormone-releasing hormone (LH-RH) analogue, in combination with an antiandrogen (flutamide), given during the first 2 weeks, followed by 70-Gy external-beam radiation therapy (EBRT) in 35 fractions. The initial 46 Gy was given with a four-field technique, while the remainder was given with a dynamic conformal technique. No adjuvant hormonal therapy (AHT) was given. The median follow-up time was 63 months. PSA levels decreased to the normal range (<4 ng/ml) after irradiation in all but one patient. The 5-year PSA failure-free survival was 34.8% according to the American Society for Therapeutic Radiology and Oncology (ASTRO) definition and it was 43.0% according to the "nadir plus 2" definition. Discordance of the results between the two definitions was seen in two patients. The 5-year overall and cause-specific survivals were 83.0% and 93.3%, respectively. No severe acute or late adverse effects were observed. Seventy Gy of EBRT following 3 months of NHT produced therapeutic results comparable to those reported in other studies which used long-term AHT. The value of long-term AHT for Japanese men should be tested in a clinical trial.
    International Journal of Clinical Oncology 10/2006; 11(5):396-402. · 1.41 Impact Factor
  • Article: The patterns of care study for breast-conserving therapy in Japan: analysis of process survey from 1995 to 1997.
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    ABSTRACT: To present the results of a process survey on breast-conserving therapy (BCT) in Japan from 1995 to 1997. From September 1998 to December 1999, data on the treatment process of 865 randomly selected BCT patients were collected by extramural audits. For primary surgery, wide excision or tumorectomy was performed in 372 patients (43.0%), and quadrantectomy or segmental mastectomy was performed in 493 patients (57%). The extent of axillary dissection was equal or beyond Level II in 590 patients (68.2%). Systemic chemotherapy was administered to 103 of 160 node-positive patients (64.4%) and 180 of 569 node-negative patients (31.6%). Tamoxifen was administered to 234 of 323 hormone receptor-positive patients (72.5%) and 68 of 130 hormone receptor-negative patients (52.3%). Photon energy of 10 MV was administered for whole breast irradiation in 38 patients (4.4%) without bolus. The extent of surgical resection for BCT was large in Japan. Pathologic assessment and the technique of radiation therapy were apparently suboptimal in some cases. Information on prognostic/predictive factors was not fully utilized to individualize systemic adjuvant therapy. Establishment and widespread use of guidelines for BCT for in Japan are desirable. Repeated surveys will demonstrate how such guidelines affect clinical practices.
    International Journal of Radiation OncologyBiologyPhysics 08/2005; 62(4):1048-54. · 4.11 Impact Factor
  • Article: Treatment planning of stereotactic radiotherapy for solitary lung tumor.
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    ABSTRACT: To analyze the stereotactic radiotherapy (SRT) plans in terms of internal target volume (ITV) and organs at risk (OARs). Treatment planning and dose distributions were analyzed using dose-volume histograms (DVHs) of ITV and OARs in 37 patients, who were treated for a solitary lung tumor with SRT. The stereotactic body frame (SBF) was used for immobilization and accurate setup. Prescription dose was 48 Gy in four fractions at the isocenter. Use of SBF limits the extent of the noncoplanar beam directions to prevent a collision with the Linac gantry. DVH analyses showed that the homogeneity index, defined as the ratio of maximum and minimum dose to ITV, ranged from 1.03 to 1.25 (mean, 1.12). The volume irradiated with 20 Gy or more (V(20)) of the lung ranged from 0.3 to 11.6% (mean, 4.4%) of the whole lung volume. The maximum dose to the other OARs ranged from 0 to 11.8 Gy (mean, 0.5-2.7) per fraction. No clinically significant complications were encountered. Despite the limitation of the beam arrangement, a homogeneous target dose distribution, while avoiding high doses to normal tissues, was obtained.
    International Journal of Radiation OncologyBiologyPhysics 05/2005; 61(5):1565-71. · 4.11 Impact Factor
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    Article: 18F-FDG and 11C-methionine PET for evaluation of treatment response of lung cancer after stereotactic radiotherapy.
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    ABSTRACT: 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.
    Annals of Nuclear Medicine 01/2005; 18(8):669-74. · 1.50 Impact Factor
  • Article: Evaluation of lung injury after three-dimensional conformal stereotactic radiation therapy for solitary lung tumors: CT appearance.
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    ABSTRACT: To evaluate the computed tomographic (CT) appearance of tumors and lung injury in patients who have undergone stereotactic radiation therapy (SRT) for solitary lung tumors. Twenty-seven patients with primary lung cancer and four with metastatic lung cancer who underwent SRT for solitary lung tumors were enrolled for evaluation. SRT was delivered by using a three-dimensional conformal technique with a stereotactic body frame. A total dose of 48 Gy was administered in four fractions during a period of 2 weeks. After SRT, follow-up CT images were obtained every 2-3 months. Radiation-induced pulmonary injuries were classified into four patterns on CT images. The minimal lung dose to areas demonstrating pulmonary injury at CT was evaluated, and the correlation between the dose and the percentage volume of the whole lung irradiated by more than 20 Gy in total (V20) was assessed by using Spearman rank correlation. Tumor shrinkage continued for 2-15 months after SRT. Asymptomatic changes in the irradiated lung were noted at CT in all patients within 2-6 months (median, 4 months) after SRT. As the pattern at pulmonary CT changed, patchy consolidation was more predominantly seen as an acute change than were slight homogeneous increase in opacity, discrete consolidation, or solid consolidation; solid consolidation was the more predominantly seen late change. The minimal lung dose to the area demonstrating pulmonary injury in each patient ranged between 16 and 36 Gy (median, 24 Gy). The dose was significantly (P <.001) inversely correlated with the V20 in each patient. The reaction to SRT of the lungs seems similar to the reaction to conventional radiation therapy.
    Radiology 01/2004; 230(1):101-8. · 5.73 Impact Factor
  • Article: Clinical evaluation of dynamic arc conformal radiotherapy for paraaortic lymph node metastasis.
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    ABSTRACT: 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 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. 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. Dynamic arc conformal radiotherapy, a simple IMRT, is a safe and effective treatment method for paraaortic lymph node metastasis.
    Radiotherapy and Oncology 05/2003; 67(1):113-8. · 5.58 Impact Factor
  • Article: Clinical outcomes of 3D conformal hypofractionated single high-dose radiotherapy for one or two lung tumors using a stereotactic body frame.
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    ABSTRACT: 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. 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). 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). 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.
    International Journal of Radiation OncologyBiologyPhysics 03/2002; 52(4):1041-6. · 4.11 Impact Factor
  • Article: Postoperative radiotherapy for intracranial ependymoma: analysis of prognostic factors and patterns of failure.
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    ABSTRACT: The long-term results of external beam radiotherapy following surgical resection in patients with intracranial ependymomas were evaluated to identify the prognostic factors and the pattern of recurrence. Between June 1961 and January 1999, 48 patients with intracranial ependymoma were treated with external beam irradiation with >40 Gy following surgery. Total doses of 40.5-63.4Gy were delivered to the tumor site in 22-46 fractions over 33-101 days. Six patients with spinal deposit or positive cerebrospinal fluid cytology received whole spinal axis irradiation, and 4 patients received prophylactic spinal irradiation. The median follow-up of surviving patients was 110 months. The 10-year overall and relapse-free survival rates were 47% and 42%, respectively. In multivariate analysis, female gender, lower tumor grade and total resection were found to be associated with better relapse-free survival. Twenty of 26 recurrences developed at the primary tumor site (inside the irradiation field), two at the unirradiated cerebellum and spinal cord, and four at the spinal cord without intracranial failure. Only one of 34 patients with supratentorial tumors developed isolated spinal metastasis, whereas 3 of 14 patients with infratentorial tumors did so. Regarding the late neurotoxicity of radiotherapy, one of the 15 long-term (>4 years) survivors whose psychosocial status could be evaluated showed marked cognitive impairment. It was suggested that the use of new treatment strategies to improve local control would be warranted, and that prophylactic whole spinal axis irradiation appeared to be of more benefit in patients with infratentorial tumors than in those with supratentorial tumors.
    Journal of Neuro-Oncology 01/2002; 56(1):87-94. · 3.21 Impact Factor
  • Article: [Three-dimensional conformal radiotherapy for extracranial tumors using a stereotactic body frame]
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    ABSTRACT: This paper was reviewed to evaluate the feasibility of three-dimensional (3-D) conformal radiotherapy for extracranial tumors, especially for solitary lung tumors using a stereotactic body frame. To extend the technique of stereotactic irradiation for intracranial tumors, accurate body fixation and regulation of internal target motion are essential. In our study, a stereotactic body frame was used, and daily setup accuracy was verified. As a result, its setup accuracy was maintained within 0-8.5 mm (Ave=2.5mm). In our initial clinical experiences for thirty-two patients with 6-10 non-coplanar static beams, forty or 48 Gy was irradiated. During the follow-up of 4-27 (Average=11) months, twenty-nine (94%) tumors were locally controlled without any symptomatic complications. Recently, respiratory-gated irradiation systems, CT-linac systems, a real-time tumor tracking system, Cyber-knife, and C-arm linac were developed. With all these techniques, stereotactic irradiation for extracranial tumors are future direction of three-dimensional conformal radiotherapy.
    Igaku butsuri: Nihon Igaku Butsuri Gakkai kikanshi = Japanese journal of medical physics: an official journal of Japan Society of Medical Physics 02/2001; 21(1):28-34.