Comparison of three treatment options for single brain metastasis from lung cancer.

Whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and the combination of both treatment methods were used for the management of single brain metastasis from lung cancer. The purpose of this study is to compare these three different treatment options in terms of local response, survival, and quality of life. From June 1995 to July 1998, 70 lung cancer patients with new diagnosed single brain metastasis were treated with either WBRT alone (n = 29), or SRS alone (n = 23), or the combination of both methods (n = 18). Multiple endpoints, including survival, freedom from local progression (FFLP), freedom from new brain metastasis (FFNBM), local control, Karnofsky performance status (KPS), and causes of death, were measured from the date of treatment completion and compared using univariate and multivariate analyses. For patients treated with WBRT-alone, SRS-alone, and SRS+WBRT, the median survivals were 5.7, 9.3, and 10.6 months, the median FFLP were 4.0, 6.9, and 8.6 months, the median FFNBM were 4.1, 6.7, and 8.6 months, and the local response rates were 55.6, 87.0, and 88.9%, respectively. Four of the 29 patients treated with WBRT-alone continued with progression of disease. The post treatment KPS showed improvement in 41.4, 82.6, and 88.9% of patients treated with WBRT-alone, SRS-alone, and SRS+WBRT, respectively. The progression of new and/or recurred metastatic brain tumor as the cause of death accounted for 51.7%, 50. 0%, and 28.3% of the patients treated with WBRT-alone, SRS-alone, and SRS+WBRT, respectively. Univariate analyses showed that the significant differences among the three treatment arms were observed based on all of the above mentioned endpoints. However, the comparison between SRS-alone and SRS+WBRT groups indicated that adding WBRT only improves FFNBM (P = 0.0392). Cox regression analyses revealed no significant difference in both of the KPS (P = 0.1082) and causes of death (P = 0.081) among the three arms. Both SRS alone and SRS+WBRT seem better in prolonging life and improving quality of life than WBRT alone for patients with single brain metastasis from lung cancer. But the combined therapy did not show significant advantage over SRS alone in improving survival, enhancing local control, and quality of life except for a more favorable FFNBM. Further investigation via a randomized trial is needed to access the value of adding WBRT to SRS in the management of this group of patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 37-45 (2000).

Preservation of visual fields after peri-sellar gamma-knife radiosurgery.

Radiosurgical treatment of pituitary and peri-sellar tumors has become an increasingly utilized modality as an alternative to conventional radiotherapy and surgery. Such radiosurgery results in a relatively high dose of radiation to the optic chiasm. The clinical data establishing safe single-fraction doses to the chiasm is immature, although taken together previous literature suggests a recommended maximal dose of 8 Gy. Optic neuropathy, when it occurs, tends to take place within 2 years of treatment. We evaluated the visual fields of 20 sequential patients that received significant doses to the optic chiasm by Gamma-knife radiosurgery. There were 17 cases of pituitary adenoma and 3 cases of meningioma, and two patients refused follow-up testing. Preoperative visual field and cranial nerve examinations were done prior to radiosurgery and in follow-up, with a median follow-up of 24 months. There were no cases of quantitative visual field deficit induced by treatment. No patients developed symptomatic visual deterioration. Radiat. Oncol. Invest. 90:343-350, 2000. 2000 Wiley-Liss, Inc.

Radiosurgery for cerebral arteriovenous malformations: assessment of early phase magnetic resonance imaging and significance of gadolinium-DTPA enhancement.

PURPOSE: To evaluate the initial changes within the nidus of arteriovenous malformations (AVMs) and to assess the reaction to the brain tissue surrounding AVMs after radiosurgery by serial magnetic resonance (MR) imaging. METHODS AND MATERIALS: Twenty-one patients, treated using 60Co gamma knife unit with cerebral AVMs, were retrospectively evaluated. Forty-seven follow-up MR images of the 21 patients were performed including 10 patients with two or more serial gadolinium enhanced studies (Gd-MR). Two or more sequential MR angiographies (MRA) were obtained in 13 patients. Three-dimensional (3D) time-of-flight MRA and two-dimensional (2D) phase contrast MRA were used in 13 patients for evaluating the flow changes of AVMs. The follow-up period after radiosurgery ranged from 3 to 30 months (average 10.8 months) and the interval time of MRI ranged from 34 days to 13 months (average 4.9 months). RESULTS: Reduction of nidus size was observed in 14 of 21 patients (67%) between 4 to 13 months on spin echo (SE) images. Complete obliteration was observed on SE images in 4 of these 14 patients; three were confirmed by conventional angiography. New hyperintense areas surrounding the nidus on T2s-weighted images (T2WI) developed in 9 of the 14 patients who showed nidus reduction between 5 to 17 months after radiosurgery; in three patients, size of the hyperintense area started to decrease between 6 to 7 months after its appearance. Probable radiation necrosis of pons developed in one patient 26 months after radiosurgery. The irradiated area within the AVM nidus was significantly enhanced in 8 of the 10 patients who underwent Gd-MR. The degrees of enhancement within the nidus increased with time in 7 of the 10 patients. Overall, total enhancement of irradiated areas was observed in four of the 10 patients; in three of the four, the enhancement decreased in size and degree, indicating nidus reduction. In three patients who had a partial volume irradiation within the nidus, the enhancing areas corresponded with the exact portions of irradiated volume. The nidus reduction was observed in 7 of the 13 patients on MRA during 5 to 13 months after radiosurgery. MRA was more useful compared to SE images in four of the seven patients in evaluating the size change of AVM nidus, feeding arteries, and draining veins. CONCLUSION: Magnetic resonance imaging and MRA were useful in assessing the progress of nidus reduction. T2-weighted imaging was sensitive to radiation-induced reaction in and around the AVM nidus. The enhancement within the AVM nidus on Gd-MR may represent the initial sign of nidus reduction and demonstrates the exact location of irradiation in the nidus. The changes of the enhancement pattern are presumed to represent the processes of nidus reduction and irradiated reaction within the AVM nidus.

Once-a-week vs conventional daily radiation treatment for lung cancer: final report.

This is the final report of a prospective randomized clinical trial which began in 1982 and explored once-a-week hypofractionation in lung cancer patients with unresectable, non-metastatic, measurable, loco-regionally advanced disease. Stratification to this protocol has been done by histology, stage, and performance status categories. Patients with ipsilateral supraclavicular and/or brain metastases as the only evidence of distant spread, have been included in the study, but were stratified and analyzed separately. The two protocol arms were: (I) Conventional daily radiation [5 x W]-5 daily fractions of 2 Gy each to a total dose of 60 Gy in 6 weeks, protecting the spinal (SC) at 45 Gy and (II) Once-a-week radiation [1 x W]-one weekly fraction of 5 Gy each to a total tumor dose of 60 Gy in 12 weeks protecting the SC at 30 Gy. A total of 150 patients have been entered. Of these, 30 pts. are inevaluable, but the reasons of non-compliance, progression of disease or death due to intercurrent disease were of equal incidence in both groups. Of the 120 evaluable patients, 63 were treated 5 x W and 57 with 1 x W therapy. Complete tumor responses are similar in both arms with 1 x W pts demonstrating a numerical advantage (26% vs 17%). The average follow-up of the entire series is 3 yrs with a range of 12-66 months. Survival data is comparable in both groups with the 12 and 24 month actuarial survival of 49% and 23% for the 5 x W arm and 59% and 29% for the 1 x W arm. 1 x W patients continue to show a better tolerance than 5 x W pts. There are sufficient long-term survivors in both arms to assess chronic toxicity. The number of patients alive at 12, 18, and 24 months were 25, 11, and 5 for the 5 x W arm and 29, 16, and 7 for the 1 x W arm. No significant differences in late reactions have been noted. The longest surviving patient in the 1 x W arm is now 48 months after treatment.

Radiation control in the intensive care unit for high intensity iridium-192 brain implants.

A bedside lead cubicle was designed to minimize the radiation exposure of intensive care unit staff during routine interstitial brain irradiation by removable, high intensity iridium-192. The cubicle shields the patient without restricting intensive care routines. The design specifications were confirmed by exposure measurements around the shield with an implanted anthropomorphic phantom simulating the patient situation. The cubicle reduces the exposure rate around an implant patient by as much as 90%, with the exposure level not exceeding 0.1 mR/hour/mg of radium-equivalent 192Ir. Evaluation of data accumulated for the past 3 years has shown that the exposure levels of individual attending nurses are 0.12 to 0.36 mR/mg of radium-equivalent 192Ir per 12-hour shift. The corresponding range for entire nursing teams varies between 0.18 and 0.26. A radiation control index (exposure per mg of radium-equivalent 192Ir per nurse-hour) is thus defined for individual nurses and nursing teams; this index is a significant guide to the planning of nurse rotations for brain implant patients with various 192Ir loads. The bedside shield reduces exposure from 192Ir implants by a factor of about 20, as expected, and the exposure from the lower energy radioisotope iodine-125 is barely detectable.

A prospective randomized trial comparing once-a-week vs daily radiation therapy for locally-advanced, non-metastatic, lung cancer: a preliminary report.

This is the first report of an on-going Phase III protocol for patients with locally-advanced, non-metastatic, measurable lung cancer. The study randomizes two arms: 6000 rad using 500 rad fractions once a week (1 X W) for 12 weeks with spinal cord (SC) protection at 3000 rad; and 6000 rad using 200 rad fractions daily (5 X W) for 6 weeks with SC protection at 4500 rad. Both arms use an initially large loco-regional field that is further reduced when tumor doses reach 3000 rad in (1 X W) arm and 5000 rad in (5 X W) arm. The protocol was activated April 1982; as of August 1984, it had accrued 100 patients of whom 68 were evaluable [29 (1 X W) and 39 (5 X W)]. There have been no major differences in tumor responses or failure patterns between the (1 X W) and (5 X W) arms; response rates have been 69 and 64%; CR 31 and 20%; total incidence of local failures 20 and 23%; and overall incidence of distant failures 34 and 43%, respectively. The (1 X W) arm has been far better tolerated with 76% of its patients free of any esophagitis and 97% without weight loss, as compared to only 33 and 67% in the (5 X W), respectively. The (1 X W) arm has not conveyed loss in tumor control effectiveness, in-treatment progression, or higher incidence of distant spread. Subacute and chronic complications have been minimal with either treatment. No fatal or life-threatening toxicities have occurred; the incidence of severe complications has been 7% in the (1 X W) arm and 8% in the (5 X W) arm. Nevertheless, the number of patients alive and at risk greater than or equal to 12 months is still relatively small; definitive statements regarding very late toxic reactions cannot yet be made. Compared to their protocyptes [a (1 X W) Pilot Study and the 6000 rad/6 weeks arm of RTOG Protocol 73-01], results in the present protocol arms have not been different from what was expected. Once a week RT yields results that appear no different from those achieved with conventional RT in lung cancer.

Technique and preliminary results of interstitial irradiation for primary brain tumors.

We have conducted a phase-I clinical trial of CT-guided stereotactic implantation of Ir192 in the treatment of malignant astrocytomas. During the past year, 16 patients have been implanted with two to four catheters in the residual enhancing portion of their tumor. These patients represent 50% of our total experience with the CT compatible Leksell frame. Each catheter contains three to six high intensity (2.0 to 2.5 mg Ra equivalent) seeds with 0.5 cm separation between the sources. The total activity of Ir192 per implant has been 30-65 mg radium equivalent. In the 16 patients, 49 catheters have been placed, an average of three targets calculated per patient and no targets have been missed. The radiation exposure to personnel has been surveyed in detail and drops off to less than 2 mr/h six feet from the patient when our custom-built radiation shield is employed. We have reserved permanent implantation of I125 for patients with tumors in unusual locations (e.g. pineal) or for individuals with slowly growing non-gliomatous lesions (i.e. meningioma). The tumor volumes have ranged from 12-120 cm3. Unique aspects of our implant procedure include the use of a Leksell frame already adapted to the GE-8800 scanner, the use of pre- and post-implant computerized treatment planning programs to determine the dose distribution profiles and the use of adjustable metal collars crimped to the outer catheters to provide ease of insertion, uniform pre-implant catheter length, and protection against source migration. Two of our patients have suffered from subacute radiation reactions, primarily due to delayed cerebral edema and both of these cases have largely resolved.(ABSTRACT TRUNCATED AT 250 WORDS)

Removable high intensity iridium-192 brain implants. Technique and in vivo measurements in canine brain.

A preclinical evaluation of the technical details and dosimetry for temporary high intensity 192Ir brain implants is presented. The canine brain was used for this quality assurance study in which direct in vivo dose measurements were done by thermoluminescent dosimetry (TLD rods). Precise and reproducible positioning of the TLD rods and 192Ir ribbons were assured by simple accessories which can be utilized in the clinical situation. The neurosurgical procedure for this non-routine interstitial implant of the brain, suitability of type and size of afterloading cannulas and facility for firmly anchoring them to the scalp, and comparison of measured doses with computer-predicted values are details assured by the canine study. Agreement between the in vivo determination and computer-generated doses was consistently in the range 2-5%. Data derived from this preclinical evaluation are currently used in both stereotactic and non-stereotactic brain implants at our institution. Details are presented for the implant procedure, dose measurements and brachytherapy planning for multiple ribbons. The latter incorporates direct interaction on computed tomography (CT) images for a hypothetical patient case.