Akio Takamura

STEREOTACTIC IRRADIATION WITHOUT WHOLE-BRAIN IRRADIATION FOR SINGLE BRAIN METASTASIS

PURPOSE The effectiveness of stereotactic irradiation (STI) alone without whole-brain irradiation (WBI) for a single metastatic brain tumor was analyzed retrospectively. METHODS AND MATERIALS Forty-four patients with this condition were treated using radiosurgery (RS) alone or fractionated stereotactic radiotherapy (FSR) without WBI. RESULTS The initial response rate was 92% and the overall local control rate was 84% (37 of 44 patients). A total of 39% (18 of 44) of patients experienced intracranial relapse outside the initial target area. Forty-eight percent (21 of 44) of patients required salvage treatment for intracranial relapse. All 7 patients who received WBI as salvage treatment required no further salvage treatment, but 5 of the 14 patients who received salvage STI without WBI required three to four treatments for brain metastasis. Late radiation damage was not seen with initial treatment but was observed with retreatment. The overall median survival time was 261 days, with a standard error of 64 days. Actuarial survival at 12 and 24 months was 34% and 9%, respectively. The actuarial survival rate was significantly affected by the existence of active extracranial disease (p = 0.041). CONCLUSION The high response rate and short treatment period of STI alone are advantageous in the treatment of single brain metastasis in patients with active extracranial disease with WBI reserved for relapse. Because of the low complication rate, STI alone may be also useful in patients with good prognosis, without extracranial disease.

The role of radiotherapy in the management of extrahepatic bile duct cancer: An analysis of 145 consecutive patients treated with intraluminal and/or external beam radiotherapy

PURPOSE To determine the feasibility of high dose radiotherapy and to evaluate its role in the management of extrahepatic bile duct (EHBD) cancer. METHODS AND MATERIALS Between 1983 and 1991, 145 consecutive patients with EHBD cancer were treated by low dose rate intraluminal 192Ir irradiation (ILRT) either alone or in combination with external beam radiotherapy (EBRT). Among the primarily irradiated, 77 patients unsuitable for surgical resection, 54 were enrolled in radical radiotherapy, and 23 received palliative radiotherapy. Fifty-nine received postoperative radiotherapy, and the remaining 9 preoperative radiotherapy. The mean radiation dose was 67.8 Gy, ranging from 10 to 135 Gy. Intraluminal 192Ir irradiation was indicated in 103 patients, and 85 of them were combined with EBRT. Expandable metallic biliary endoprosthesis (EMBE) was used in 32 primarily irradiated patients (31 radical and 1 palliative radiotherapy) after the completion of radiotherapy. RESULTS The 1-, 3-, and 5-year actuarial survival rates for all 145 patients were 55%, 18%, and 10%, for the 54 patients treated by radical radiotherapy (mean 83.1 Gy), 56%, 13%, and 6% [median survival time (MST) 12.4 months], and for the 59 patients receiving postoperative radiotherapy (mean 61.6 Gy), 73%, 31%, and 18% (MST 21.5 months), respectively. Expandable metallic biliary endoprosthesis was useful for the early establishment of an internal bile passage in radically irradiated patients and MST of 14.9 months in these 31 patients was significantly longer than that of 9.3 months in the remaining 23 patients without EMBE placement (p < 0.05). Eighteen patients whose surgical margins were positive in the hepatic side bile duct(s) showed significantly better survival compared with 15 patients whose surgical margins were positive in the adjacent structure(s) (44% vs. 0% survival at 3 years, p < 0.001). No survival benefit was obtained in patients given palliative or preoperative radiotherapy. Gastroduodenal complications increased in those receiving doses of 90 Gy or more, and serious biliary bleeding was experienced in three preoperatively irradiated patients. Complications in other patients was tolerable. CONCLUSIONS High-dose radiotherapy, consisting of ILRT and EBRT, appears to be feasible in the management of EHBD cancer, and it offers a survival advantage for patients not suited for surgical resection and patients with positive margins in the resected end of the hepatic side bile duct. Expandable metallic biliary endoprosthesis assists the internal bile flow and may lengthen survival after high dose radiotherapy.

Intraluminal low-dose-rate 192Ir brachytherapy combined with external beam radiotherapy and biliary stenting for unresectable extrahepatic bile duct carcinoma

PURPOSE To evaluate the results of combined-modality therapy, including external beam radiotherapy, intraluminal (192)Ir, and biliary stenting for extrahepatic bile duct carcinoma. MATERIALS AND METHODS Between 1988 and 1998, 93 patients with unresectable extrahepatic bile duct carcinoma underwent definitive radiotherapy. The dose of external beam radiotherapy was 50 Gy in 25 fractions. Low-dose-rate (192)Ir was delivered at a dose of 27-50 Gy (mean 39.2) at 0.5 cm from the source. An expandable metallic endoprosthesis was used to establish an internal bile passage. RESULTS The median survival was 12 months, with a 1-, 3-, and 5-year actuarial survival rate of 50%, 10%, and 4%, respectively. Tumor length, hepatic invasion, and distant metastasis significantly affected survival. Ninety-six percent of patients could successfully remove external drainage catheters. The actuarial biliary patency rate for these patients at 1, 3, and 5 years was 52%, 29%, and 18%, respectively. Tumor length, tumor diameter and T stage were significantly associated with the patency rate. Mild-to-severe gastroduodenal complications were observed in 32 patients and were significantly associated with the active length of (192)Ir and linear source activity. Eight patients had treatment-related biliary fistula. CONCLUSIONS Our combined-modality therapy provided reasonable local control and improved the quality of life of patients with extrahepatic bile duct carcinoma. Because none of the treatment characteristics had any impact on survival or biliary patency, lower dose levels and/or a localized target volume are recommended to minimize morbidity.

Improved results in the treatment of nasopharyngeal carcinoma using combined radiotherapy and chemotherapy.

A total of 77 patients with nasopharyngeal carcinoma were retrospectively reviewed for the effectiveness of combining chemotherapy (CT) with radical radiotherapy (RT). From 1972 to 1976, 26 patients were treated with a relatively short course of radical RT alone: 52–55 Gy/16 Fx/4 wk (study 1). From 1977 to 1982, 29 patients were also treated with radical RT alone, but with a more prolonged fractionation schedule: 65–70 Gy/26–28 Fx/6.5–7 wk (study 2). In 1983, the policy was to combine CT and RT. From 1983 to 1987, 22 patients received four to six courses of CMU regimen (consisting of cyclophosphamide, methotrexate, and UFT, a 5‐fluorouracil analog) after completion of radical RT (study 3). The three studies were comparable with regard to patient characteristics: histologic type, stage, sex, and age distribution. There were no significant differences in survival and relapse figures between study 1 and study 2, but study 3 compared favorably with study 1 and study 2 in actuarial survival, relapse‐free survival, relapse rate, and median relapse time. A mild nausea and transient granulocytopenia during CT was the only side effect encountered. In conclusion, the use of CT in combination with RT appeared to increase significantly the chance of long‐term survival and probable cure.

The value of treatment planning using CT and an immobilizing shell in radiotherapy for paranasal sinus carcinomas

This article describes a method which uses CT scans and immobilizing shells radiation treatment planning (CT-assisted planning) for paranasal sinus carcinomas and the value of this method on the treatment outcome. Results of the treatment for 82 patients who had CT-assisted planning were compared with that of 88 patients who had no such treatment planning. It has been concluded that the combined use of CT and the shell in treatment planning permitted a 3-dimensional localization of both the tumor and critical normal structures with great accuracy, leading to an improved long-term survival and a reduced complication rate. The multivariate regression analysis for predicting significant prognostic factors also confirmed the valuable role of CT in terms of survival and primary tumor control. The actuarial 5-year survival rate was 51% in all patients, whereas, by using CT-assisted planning, it was improved to 61%. The improved survival was observed among the patients with tumors of the suprastructures where tumors were located adjacent to the critical organs (brain and eye). Major complications attributable to radiation have included instances of brain and ocular damage. CT-assisted planning, however, has been proven effective in avoiding brain necrosis and preserving eye sight.

High-dose-rate intracavitary irradiation using linear source arrangement for stage II and III squamous cell carcinoma of the uterine cervix

PURPOSE The purpose of this article is to evaluate fractionated high-dose-rate (HDR) intracavitary irradiation using linear source arrangement (LSA) for patients with squamous cell carcinoma of the uterine cervix. MATERIALS AND METHODS The subjects consisted of 217 patients (71 patients with stage II and 146 with stage III disease) who received external beam therapy (EBT) followed by fractionated HDR intracavitary irradiation using LSA between January 1980 and June 1990. In EBT, 40 Gy in 20 fractions (40 Gy/20 Fr) or 39.6 Gy/22 Fr was delivered to the whole pelvis and an additional 10 Gy/5 Fr or 10.8 Gy/6 Fr was delivered to the parametrium. The intracavitary irradiation dose was 30 Gy/6 Fr or 35 Gy/7 Fr with a daily fraction size of 5 Gy and two fractions per week. During the intracavitary treatment, most patients were treated on an out-patient basis. RESULTS Cause-specific 5-year survival rates were 77% for stage II and 50% for stage III. Pelvic failure rates were 13% for stage II and 36% for stage III. In multivariate analyses, improved cause-specific survival was significantly associated with stage II (P = 0.0003), higher pretreatment serum hemoglobin level (P = 0.0015), higher pretreatment serum total protein level (P = 0.0029), and shorter total treatment time (P = 0.0024). The rate of severe (grade 3 or 4) late complication was 2% for the rectum, 1% for the small intestine or sigmoid colon and 1% for the bladder. CONCLUSIONS Fractionated HDR intracavitary irradiation using LSA is an effective treatment for patients with uterine cervical cancer without need for hospitalization.

Intraoperative radiation therapy to the upper mediastinum and nerve-sparing three-field lymphadenectomy followed by external beam radiotherapy for patients with thoracic esophageal carcinoma

In patients with thoracic esophageal carcinoma, radical dissection of the upper mediastinal lymph nodes often leads to complications such as recurrent laryngeal nerve palsy and subsequent pulmonary disorders. Intraoperative radiation therapy (IORT) to the upper mediastinum and nerve‐sparing three‐field lymphadenectomy followed by external beam radiotherapy has been developed to improve the locoregional control rate without resulting in these major postoperative complications.

Intraoperative radiotherapy for esophageal carcinoma— Significance of tort dose for the incidence of fatal tracheal complication

PURPOSE The feasibility of intraoperative radiotherapy (IORT) combined with modified regional lymphatic dissection (plus esophagectomy) for advanced esophageal carcinoma was tested. The quality of life in the patients was expected to improve by modified surgery, securing a good local control by additional IORT. METHODS AND MATERIALS Total esophagectomy plus modified three-regional lymphatic dissection with upper mediastinal IORT followed by postoperative external beam irradiation was systematically given to 62 patients between August 1989 and June 1992. Sixty-five percent of the patients were age over 60, and 76% (47/62) of the patients were Stage III or IV by pTNM. Several techniques for the IORT were developed and used throughout this period, including a temporary collapse of the right lung by unilateral tracheal incubation (for the insertion of IORT applicator) and an in vivo dosimetry to know the appropriate range (energy) of electron beam. The method of surgical treatment, the dose of external beam irradiation were kept standardized, and only the dose of IORT was randomized either to 20 or 25 Gy. IORT-related complications and the pattern of failures were carefully monitored. RESULTS (a) Most prominent IORT-related complication was the late tracheal damage, which occurred 6 of 44 patients who were at risk for more than a year. (b) The incidence of IORT-induced tracheal damage was sharply dependent on the dose of IORT; 6 out of 21 patients who received single dose of 25 Gy, and none out of 33 who were given 20 Gy or less. (c) 2-year cause-specific survival and actuarial 2-year survival were 75.0 +/- 14.5% and 62.5 +/- 13.2%, respectively. No loco-regional recurrence has been detected at the time of analysis. CONCLUSION IORT in combination with modified total esophagectomy is an effective and safe method to obtain a local control in advanced esophageal carcinomas, if the dose of IORT does not exceed 20 Gy.

Factors associated with tumor response and survival in radiosurgery for brain metastasis

BackgroundWe reviewed our experience with radiosurgery for brain metastasis and focused on factors associated with tumor response and survival.MethodsOur study consists of 19 patients with 25 brain metastases who underwent linear accelerator radiosurgery. There was evidence of extra-central nervous system (CNS) tumors in 15 patients. The maximum diameter of the tumors ranged from 3 to 40 mm with a mean of 20 mm. Tumor doses at the isocenter varied from 16 to 25 Gy with a mean of 21 Gy. Eighteen lesions were treated by radiosurgery alone and 7 lesions received combined radiosurgery with fractionated radiotherapy. Of the 11 patients who experienced CNS failure either in or out of the radiosurgery field, 6 patients had salvage radiotherapy.ResultsMedian survival was 7 months, and the 1-year actuarial survival rate was 40%. Death was due to extra-CNS tumor manifestations in 11 patients. In 3 patients, CNS failure was the cause of death. One died of local progression, and the other 2 died of newly developed metastases. Poor Karnofsky performance scores and the presence of extra-CNS tumors significantly affected 1-year survival in univariate analysis (P<0.05). Local tumor control was achieved in 80% of the lesions. The 1-year actuarial tumor control rate was 51%. Newly developed brain metastases were observed in 7 patients. The tumor diameter was mostly associated with tumor response in multiple regression analysis (P=0.0031).ConclusionWe concluded that radiosurgery is effective in controlling small brain metastasis. Survival benefit is expected for those with good performance status and adequately controlled extra-CNS disease.

Tc-99m HMPAO uptake in renal cell carcinoma metastases

A 77-year-old man with renal cell carcinoma underwent Tc-99m HMPAO scintigraphy to evaluate a brain mass seen on CT scan after radiation therapy. Tc-99m HMPAO SPECT imaging showed intense accumulation in the nasal cavity and in the parietal bone. These lesions were well seen on CT with contrast enhancement and were thought to be suggestive of hypervascularity. They were in fact hypervascular. The tumor in the nasal cavity had been histologically proven to be a metastasis from a renal cell carcinoma.