Atsuro Terahara

Megavoltage CT-assisted stereotactic radiosurgery for thoracic tumors: original research in the treatment of thoracic neoplasms.

PURPOSE The aim of the study was to evaluate the efficacy of stereotactic radiosurgery (SRS) for thoracic tumors with megavoltage computed tomography (MVCT) from the point of view of symptom palliation as well as local control. METHODS AND MATERIALS MVCT-assisted positioning verification and real-time monitoring for a multileaf collimator (MLC) were used to enhance the accuracy of the thoracic SRS. Twenty-two thoracic tumors in 15 patients underwent the present treatment. All but 1 tumor were metastases from various primary malignancies. Eleven patients were symptomatic. The treatment site was the chest wall/pleura in 10 tumors, and the lung in 12 tumors. The median volume of the clinical target was 4.5 cc and the median peripheral dose was 20 Gy, for the lung tumors. For the chest wall/pleura tumors, the median volume of the clinical target was 40 cc and the median peripheral dose was 20 Gy. Conventional fractionated conformal radiation therapy (CRT) followed SRS in 10 tumors. RESULTS Of 21 tumors eligible for evaluation, there were 13 with complete responses, 6 with partial responses, and 2 without response. Duration of local control ranged from 0.6 to 82 months with a median of 8 months, with only one local recurrence seen. Immediate palliation was obtained in most symptomatic patients. Interstitial changes in the lung were limited. Autopsy performed for a patient revealed remarkable histologic effects with minimal injuries to the lung. CONCLUSION The geometric accuracy of MVCT-assisted SRS appeared to enhance the clinical efficacy and safety of treatment to thoracic malignancies.

Results of radiosurgery for brain stem arteriovenous malformations.

OBJECTIVE To assess the treatment results of radiosurgery for brain stem arteriovenous malformations (AVMs) and to seek optimal dose and treatment volume prescription for these lesions. METHODS The clinical and radiological data of 30 consecutive patients with brain stem AVM treated with gamma knife radiosurgery were retrospectively reviewed with a mean follow up period of 52.2 months. There were 26 patients with previous haemorrhages and 21 with neurological deficit. Seventeen AVMs were located in the midbrain, 11 in the pons, and two in the medulla oblongata. All of the lesions were small with the intra-axial component occupying less than one third of the area of brain stem parenchyma on axial section of multiplaner MRI or CT. The mean diameter of the nidus was 1.26 cm, and the nidus volume within the brain stem parenchyma ranged from 0.1 to 2.0 cm3. The mean radiation dose to the AVM margin was 18.4 Gy. RESULTS The actuarial 3 year obliteration rate was 52.2%; 69.4% in cases treated with standard doses (minimum target dose, 18–20Gy), and 14.3% in cases treated with low doses (<18 Gy) (p<0.05). Two patients sustained symptomatic radiation injury, but there was no permanent neurological deficit caused by radiosurgery. Five patients had haemorrhage from the AVM after irradiation, including four fatal cases, resulting in a 4.0% annual rate of post-treatment bleeding. CONCLUSIONS Radiosurgery is a viable treatment modality for patients with small deep parenchymal brain stem AVMs. A standard radiosurgical dose is safe and effective when directed to a small treatment volume. However, latent interval haemorrhage remains a significant problem until the nidus is obliterated completely.

Control of epilepsy associated with cerebral arteriovenous malformations after radiosurgery

OBJECTIVE To investigate the effect of radiosurgery for symptomatic epilepsy associated with cerebral arteriovenous malformations (AVMs). METHODS Thirty five patients with unruptured epileptogenic AVMs were studied with a mean follow up of 43.0 months. The duration of epilepsy before radiosurgery ranged from 2 months to 21 years (mean 2.8 years). Fifteen patients showed partial seizures; eight of these had associated secondary generalisation. The remaining 20 patients showed only generalised seizures without preceding focal seizures. RESULTS At the final follow up examination, 28 patients remained seizure free, whereas seizures continued in seven. Variables significantly associated with continuity of seizures after radiosurgery were the number of seizures before therapy (p<0.01) and duration of epilepsy (p<0.05). According to Engel’s classification, the 10 patients with intractable seizures before treatment included five with grade I, four with grade III, and one with grade IV. The frequency of seizures began to decrease several months after radiosurgery; much shorter than the time required for morphological change in the AVMs. CONCLUSIONS Radiosurgery seems to be beneficial for seizure control in patients with unruptured epileptogenic AVM.

Radiation therapy in early glottic carcinoma: uni- and multivariate analysis of prognostic factors affecting local control.

PURPOSE The purpose of this report is to clarify prognostic factors affecting local control of T1 and T2 glottic tumors and to define an optimal regimen for radiation therapy. METHODS AND MATERIALS Two hundred and ten patients (199 males, 11 females, age range 30 to 86 years with an average of 62 years) with previously untreated invasive squamous cell carcinoma of the glottis were treated with radiation therapy at the University of Tokyo between January 1972 and December 1989. Endoscopic microsurgery was introduced as an integral part of treatment in 1974. From 1974 to 1979 the radiation dose was gradually reduced, reaching a mean of 20 Gy in 2 weeks in 1979. From 1980 to 1983, the total dose increased to 50.4 Gy, with a fraction size of 1.8 Gy, over a mean of 5.6 weeks. From 1984 onward, the mean total radiation dose increased to 60 Gy with a fraction of 2 Gy. RESULTS Recurrence-free 5 year survival rates for T1a, T1b, and T2 were 79%, 73%, and 67%, respectively. When the relationship between radiation dose and local control rates was analyzed for each year from 1974 to 1989, total doses were strongly associated with local control for patients with T1a disease. Age, sex, daily dose, total dose, radiation machine (Co-60 or 10 MV Lineac), treatment technique (anterior wedged pair or parallel opposed fields), treatment volume, use of endoscopic microsurgery, and involvement of the anterior commissure were examined for effects upon relapse-free survival in T1a disease by uni- and multivariate analysis. Total dose was the only significant factor for T1a disease (p < 0.02). The effect of these variables upon relapse-free survival in T2 disease as well as the effect of cord mobility, and number of involved sites was examined by multivariate analysis. Total dose (p < 0.03), cord mobility (p < 0.05), and number of involved sites (p < 0.04) significantly affected relapse-free survival in T2 disease. CONCLUSION At least 50 Gy is required for treatment of T1 disease when 2 Gy is used as a daily dose, even if endoscopic microsurgery is performed. Better local control of T2 disease in patients with impaired cord mobility or more than three involved sites leads to an improved prognosis; we recommend doses of at least 70 Gy or use of hyperfractionation in such patients with these factors. Although the daily dose did not significantly affect prognosis in multivariate analyses, 1.8 Gy is not recommended for treatment of T2 tumors instead of 2 Gy.

Prescreening based on the presence of CT-scan abnormalities and biomarkers (KL-6 and SP-D) may reduce severe radiation pneumonitis after stereotactic radiotherapy

PurposeTo determine the risk factors of severe radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT) for primary or secondary lung tumors.Materials and methodsFrom January 2003 to March 2009, SBRT was performed on 117 patients (32 patients before 2005 and 85 patients after 2006) with lung tumors (primary = 74 patients and metastatic/recurrent = 43 patients) in our institution. In the current study, the results on cases with severe RP (grades 4-5) were evaluated. Serum Krebs von den Lungen-6 (KL-6) and serum Surfactant protein-D (SP-D) were used to predict the incidence of RP. A shadow of interstitial pneumonitis (IP) on the CT image before performing SBRT was also used as an indicator for RP. Since 2006, patients have been prescreened for biological markers (KL-6 & SP-D) as well as checking for an IP-shadow in CT.ResultsGrades 4-5 RP was observed in nine patients (7.7%) after SBRT and seven of these cases (6.0%) were grade 5 in our institution. A correlation was found between the incidence of RP and higher serum KL-6 & SP-D levels. IP-shadow in patients CT was also found to correlate well with the severe RP. Severe RP was reduced from 18.8% before 2005 to 3.5% after 2006 (p = 0.042). There was no correlation between the dose volume histogram parameters and these severe RP patients.ConclusionPatients presenting with an IP shadow in the CT and a high value of the serum KL-6 & SP-D before SBRT treatment developed severe radiation pneumonitis at a high rate. The reduction of RP incidence in patients treated after 2006 may have been attributed to prescreening of the patients. Therefore, pre-screening before SBRT for an IP shadow in CT and serum KL-6 & SP-D is recommended in the management and treatment of patients with primary or secondary lung tumors.

Role of radiosurgery in the management of cavernous sinus meningiomas.

Objective ‐ To provide our early experience and philosophy in the utility of radiosurgery in the management of cavernous sinus meningiomas. Methods ‐ Twenty‐five consecutive cases with cavernous sinus meningiomas treated between 1990 and 1995 were reviewed. Three cases were treated with gamma‐knife radiosurgery, 15 with preceding surgery and gamma knife, 7 with surgery. Mean follow‐up following radiosurgery and surgery were 34.8 and 25.4 months, respectively. Results ‐ The 5‐year actuarial tumor control rate following radiosurgery was 85.7% and tumor remission rate was 61.4%. Permanent neurological deterioration after radiosurgery was seen in 1 case (5.9%), whereas newly developed or worsened neurological deficits permanently persisted in 59.1% of patients after surgery. There was a clear correlation between surgical radicality and postoperative morbidity rate. Conclusions ‐ Gamma‐knife radiosurgery is a valuable addition to surgical removal in the treatment of cavernous sinus meningiomas. Combination of non‐radical resection and subsequent radiosurgery is recommended to improve treatment‐associated morbidity.

Quality assurance of volumetric modulated arc therapy using Elekta Synergy

Purpose. Recently, Elekta has supplied volumetric modulated arc therapy (VMAT) in which multi-leaf collimator (MLC) shape, jaw position, collimator angle, and gantry speed vary continuously during gantry rotation. A quality assurance procedure for VMAT delivery is described. Methods and materials. A single-arc VMAT plan with 73 control points (CPs) and 5-degree gantry angle spacing for a prostate cancer patient has been created by ERGO + + treatment planning system (TPS), where MLC shapes are given by anatomic relationship between a target and organs at risk and the monitor unit for each CP is optimized based on given dose prescriptions. Actual leaf and jaw positions, gantry angles and dose rates during prostate VMAT delivery were recorded in every 0.25 seconds, and the errors between planned and actual values were evaluated. The dose re-calculation using these recorded data has been performed and compared with the original TPS plan using the gamma index. Results. Typical peak errors of gantry angles, leaf positions, and jaw positions were 3 degrees, 0.6 mm, and 1 mm, respectively. The dose distribution obtained by the TPS plan and the recalculated one agreed well under 2%-2 mm gamma index criteria. Conclusions. Quality assurance for prostate VMAT delivery has been performed with a satisfied result.

Thermoradiotherapy in the treatment of locally advanced nonsmall cell lung cancer

PURPOSE To improve the treatment results of locally advanced non-small cell lung cancer (NSCLC), we have been conducting a clinical trial using regional hyperthermia combined with radiotherapy. METHODS AND MATERIALS Between 1985 and 1990, 19 patients were treated. All cases except one were regarded as initially unresectable. There were 10 Stage IIIA cases and nine Stage IIIB cases. In 10 cases thermoradiotherapy was used definitively, and in the other nine cases preoperatively. Radiotherapy was administered with conventional fractionation. Total dose ranged from 42 to 80 Gy (mean 62.9 Gy) for definitive treatment cases, and 38 to 47 Gy (mean 40.6 Gy) for preoperative cases. Radiofrequency (RF) capacitive hyperthermia was administered twice weekly, immediately after radiotherapy. Total sessions of hyperthermia ranged from 5 to 16 times (mean 9.0) for definitive treatment cases and 3 to 8 times (mean 6.7) for preoperative cases. RESULTS The results of thermoradiotherapy group (HTRT group) were compared with our historical control group (RT group); initially unresectable Stage III NSCLC irradiated definitively with 50 Gy or more (26 cases), or became resectable after radiotherapy and operated (4 cases). As for initial response, there were 5 complete responses (CRs), 13 partial responses (PRs), and 1 no change (NC) (CR rate 26%, response rate 95%) in the HTRT group, whereas there were no CR, 21 PRs, and 9 NCs in the RT group (CR rate 0%, p < 0.005, response rate 70%, p < 0.05). Overall 3-year local relapse-free survival and survival rate for the HTRT group was 73% and 37%, respectively, and 20% and 6.7%, respectively, for the RT group (p < 0.01, p < 0.01). The rate of death from uncontrolled primary disease for the HTRT group was significantly lower than for the RT group (21% vs. 53%, p < 0.03). CONCLUSION Although the number of cases is rather small, thermoradiotherapy in the treatment of locally advanced NSCLC is promising in raising resectability, local control, and, thus, long-term survival.

Japanese Structure Survey of Radiation Oncology in 2005 Based on Institutional Stratification of Patterns of Care Study

PURPOSE To evaluate the structure of radiation oncology in Japan in terms of equipment, personnel, patient load, and geographic distribution to identify and improve any deficiencies. METHODS AND MATERIALS A questionnaire-based national structure survey was conducted between March 2006 and February 2007 by the Japanese Society of Therapeutic Radiology and Oncology. These data were analyzed in terms of the institutional stratification of the Patterns of Care Study. RESULTS The total numbers of new cancer patients and total cancer patients (new and repeat) treated with radiotherapy in 2005 were estimated at approximately 162,000 and 198,000, respectively. In actual use were 765 linear accelerators, 11 telecobalt machines, 48 GammaKnife machines, 64 60Co remote-controlled after-loading systems, and 119 192Ir remote-controlled after-loading systems. The linear accelerator systems used dual-energy function in 498 systems (65%), three-dimensional conformal radiotherapy in 462 (60%), and intensity-modulated radiotherapy in 170 (22%). There were 426 Japanese Society of Therapeutic Radiology and Oncology-certified radiation oncologists, 774 full-time equivalent radiation oncologists, 117 medical physicists, and 1,635 radiation therapists. Geographically, a significant variation was found in the use of radiotherapy, from 0.9 to 2.1 patients/1,000 population. The annual patient load/FTE radiation oncologist was 247, exceeding the Blue Book guidelines level. Patterns of Care Study stratification can clearly discriminate the maturity of structures according to their academic nature and caseload. CONCLUSIONS The Japanese structure has clearly improved during the past 15 years in terms of equipment and its use, although the shortage of manpower and variations in maturity disclosed by this Patterns of Care Study stratification remain problematic. These constitute the targets for nationwide improvement in quality assurance and quality control.

A single institutional outcome analysis of Gamma Knife radiosurgery for single or multiple brain metastases

Although Gamma Knife stereotactic radiosurgery (SRS) is widely used for metastatic brain tumors, optimal patient selection and treatment strategy continue to be investigated. The aim of this study was to provide treatment results with Gamma Knife SRS and to establish prognostic factors. Of the 54 patients treated from 1990 to 1997, 51 patients were evaluable. There were 28 males and 23 females, with a median age of 60 years. Median Karnofsky Index was 80. There were 19 non-small cell lung cancers, eight colon cancers, six renal cell cancers, five ovarian cancers, four gastric cancers, three breast cancers, and six others. Primary tumors were controlled in 33 patients, and extracranial tumors were absent in 25 patients. Sixty-eight metastatic brain tumors in 37 patients underwent SRS as an initial treatment for the brain metastasis. Brain metastasis was solitary in 32 patients. Conventional radiation was combined with SRS in 29 patients, 24 of whom received whole brain radiotherapy. Eight patients had some form of surgical resection. Median survival time was 7.4 months. Five-year actuarial survival and local control rates were 16 and 52%, respectively. Median duration time of keeping pretreatment quality of life was 6.9 months. On a multivariate analysis, uncontrolled primary tumor, combined conventional radiotherapy, and performance status were statistically significant prognostic factors. Four patients who underwent whole brain radiation developed low grade dementia.