Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery

OBJECTIVE: Stereotactic radiosurgery is increasingly being used to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. The purpose of this study was to retrospectively evaluate the effectiveness of radiosurgery in the treatment of hemangioblastomas. METHODS: From 1989 to 1996, 29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated with linear accelerator-based radiosurgery. The mean patient age was 40 years (range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy (range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic and magnetic resonance imaging scans. The mean follow-up period was 43 months (range, 11-84 mo). RESULTS: Only one (3%) of the treated hemangioblastomas progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%) remained unchanged in size. Five of nine patients with symptoms referable to treated hemangioblastomas experienced symptomatic improvement. During the follow-up period, one patient died as a result of progression of untreated hemangioblastomas in the cervical spine. Three patients developed radiation necrosis, two of whom were symptomatic. CONCLUSION: Although follow-up monitoring is limited, stereotactic radiosurgery provides a high likelihood of local control of hemangioblastomas and is an attractive alternative to multiple surgical procedures for patients with von Hippel-Lindau disease.     

Effects of gamma knife radiosurgery for brain tumors: clinical evaluation

BACKGROUND: Gamma knife radiosurgery is a safe and effective alternative to microsurgery in the management of selected intracranial lesions. In our initial three-year experience with gamma knife radiosurgery, 431 patients were treated using this method. This report presents the treatment results for three different types of brain tumors: benign meningiomas, malignant metastases and gliomas. METHODS: A retrospective study was performed to analyze a consecutive series of 71 meningiomas, 31 metastatic tumors and 21 gliomas treated by gamma knife radiosurgery between March 1993 and May 1996. The treatment results were investigated using regular magnetic resonance examinations and tumor volume measurement at six-month intervals to observe sequential changes of the tumors. Patients with meningiomas were further divided into three groups according to the peripheral radiation doses: high-dose (20-17 Gy, n = 18), medium-dose (16-15 Gy, n = 33) and low-dose (14-12 Gy, n = 20). The Generalized Estimation Equation was applied to compare treatment results in these three groups with different doses and tumor volumes. RESULTS: Volume measurements of the 71 meningiomas showed that 76% decreased in size, 16% stabilized and 8% increased in size. The volumes increased most frequently in the early stage (6-12 months) after treatment and subsequently regressed after the twelfth month. The tumor control rate for meningiomas in our three-year follow-up was over 90%. For meningiomas, the statistical analysis showed that both the radiation dose and tumor volume were significantly related to the development of adverse radiation effects (p < 0.05). In metastatic tumors, rapid tumor regression after radiosurgery was found in 87% of the patients. In gliomas, radiosurgery effectively inhibited tumor growth in selected patients with small, circumscribed, less infiltrative tumors. Ependymomas and low-grade astrocytomas had more favorable outcomes than other gliomas. CONCLUSIONS: Gamma knife radiosurgery is effective for controlling tumor growth in benign meningiomas for up to three years after surgery. In selected cases of malignant metastasis and gliomas, most patients appeared to benefit from the treatment with symptomatic improvement and prolonged survival. Treatment strategy and dose selection in radiosurgery should be adjusted to optimize tumor control and avoid adverse radiation effects.     

Pharmacokinetics of the PDGF-antagonist trapidil in patients with and without renal impairment

BACKGROUND: From July 1989 to February 1996, 130 patients underwent stereotactic radiosurgery. We report the results of the first 50 patients eligible for a minimum of three years of follow-up. METHODS: Twenty women and 30 men, (mean age: 37.5 years) were treated by dynamic rotation on a 6 MV linear accelerator. Prior treatment was embolization in seventeen, surgery in three and embolization and surgery in six. All had DSA and enhanced CT scanning, while some had MRI. Forty-seven treatments used a single isodose. Restricting eloquent normal tissue to 15 Gy, margin doses (at 50-90% isodose) were 12 Gy (one patient); 15 Gy (sixteen patients); 20 Gy (31 patients); 25 Gy (two patients). Maximum diameters were: < 1.5 cm (12 patients); < 2.0 cm (nine patients); < 2.5 cm (twelve patients); < 3.0 cm (thirteen patients; 3.0 cm (four patients). RESULTS: Forty-five patients were evaluable at three years, with thirty-nine having angiography. Twenty-five had angiographically confirmed obliterations; two had parenchymal AVMs obliterated but with residual dural components; four had MRI evidence of obliteration (refused angiography). One patient acutely had a seizure; one patient (with hemorrhages, resection, and embolizations preceding two applications of radiosurgery, separated by 3.5 years) had worsening of memory. CONCLUSIONS: Our uncorrected (five patients unevaluable at three years) and corrected angiographically confirmed obliteration rates are 54% and 60% respectively. Our follow-up (98% accounting of cohort; 78% angiographic rate) and explicit derivation of denominators help delineate the efficacy of radiosurgery at these doses.     

Pathological changes in surgically resected angiographically occult vascular malformations after radiation

OBJECTIVE: The goal of this study was to evaluate the pathological changes associated with radiation treatment (stereotactic radiosurgery or conventional irradiation) of angiographically occult vascular malformations (AOVMs). METHODS: Eleven patients underwent surgical resection of an AOVM in the mesial temporal lobe, brain stem, thalamus, or basal ganglia after previous radiation treatment. The indications for surgery were recurrent symptomatic bleeding from the lesion in 10 patients and recurrent intractable seizures in 1 patient. Radiation was used as the initial therapy because the risk of surgical resection was deemed too high. Three patients received conventional radiation therapy of 3000 to 5400 rads at an outside institution. One patient received radiosurgery with the gamma knife at another institution using a dose of 15 Gy to the margin. The remaining 7 patients received stereotactic radiosurgery with a helium-ion particle beam. The dose range was from 18 to 26 Gy equivalents. The interval from radiation to surgical resection ranged from 1 to 10 years, with a mean of 3.5 years. These lesions were compared with 10 nonirradiated cavernous malformations. RESULTS: One irradiated lesion was identified pathologically as a true arteriovenous malformation despite being angiographically occult. This lesion did not demonstrate significant changes in the vasculature but did have radiation necrosis of the surrounding brain 5 years after 25 Gy equivalents of helium-ion radiosurgery. Two other specimens were too small to identify the type of vascular malformation adequately. Of the remaining eight malformations identified as cavernous malformations, six showed a combination of marked fibrosis of the vascular channels, fibrinoid necrosis, and ferrugination. However, the fibrinoid necrosis was the only finding unique to the irradiated lesions compared with nonirradiated controls. All the irradiated lesions still had patent vascular channels; none were completely thrombosed. CONCLUSION: Radiosurgery or conventional radiation therapy did not cause histologic vascular obliteration in intracranial AOVMs evaluated 1 to 10 years (mean 3.5 yr) after radiation delivery. It should be recognized that these patients are irradiation failures who may not be representative of all irradiated patients. However, recurrent bleeding from AOVMs may relate to poor radiation response in some patients.     

The effect of oral contraceptive use on the prognosis of node positive breast cancer patients. German Breast Cancer Study Group

The photon radiosurgery system is a miniature X-ray generator that can be placed stereotactically and intraoperatively into intracranial tumors to deliver a single fraction of high-dose interstitial irradiation. This battery-powered device produces low energy X-ray photons in a spherical and symmetrical pattern at the probe tip. Dose rates of up to 200 cGy/Mim are possible, allowing for the administration of 15 Gy to a lesion 3 cm in diameter in less than 1 hr. Background exposure is minimal, and no special shielding of the patient or health care personnel is required. Thirty-nine patients with brain tumor were treated in this method. There were no adverse effects. During the follow-up period of 1-30 months, 3 cases with 5 metastatic brain tumors died about 8 months after this treatment. Five recurrent cases of 21 malignant gliomas died about 4 months after treatment. Interstitial radiotherapy using photon the radiosurgery system promises to be a useful treatment for brain tumors.     

Stereotactic radiosurgery for tentorial meningiomas

Radical microsurgical resection is the procedure of choice for tentorial meningiomas. Despite advances in microsurgery, tentorial meningiomas continue to challenge surgeons and patients. To evaluate the response of tentorial meningiomas, we evaluated 41 patients who had Gamma knife stereotactic radiosurgery during a 9 year period. Patient age varied from 32 to 79 years. Headache, trigeminal neuralgia, or facial paraesthesia were the most common presenting symptoms. Sensory deficits in the distribution of the trigeminal nerve were the most common finding. Eighteen patients (44%) had undergone between 1 and 5 (mean, 1.9) resections prior to radiosurgery; 23 had tumors diagnosed by neuroimaging. The average tumor diameter in this series was 20 mm. The maximum tumor dose varied from 24 to 40 Gy (mean, 30.5 Gy), and the tumor margin dose varied from 12 to 20 Gy (mean, 15.3 Gy). During the average follow-up interval of 3 years (range, 1-8 years), 19 patients had clinical improvement, 20 remained stable, and 2 patients deteriorated. Follow-up imaging showed a reduction in tumor size in 18 patients, no further tumor growth in 22, and an increase in tumor size in one (overall tumor control rate of 98%). Stereotactic radiosurgery using the Gamma Knife was a safe and effective primary or adjuvant treatment for patients with tentorial meningiomas.     

Radiation therapy in the management of desmoid tumors

PURPOSE: To evaluate the outcome of patients with extra-mesenteric desmoid tumors treated with radiation therapy, with or without surgery. METHODS AND MATERIALS: The outcome for 75 patients receiving radiation for desmoid tumor with or without complete gross resection between 1965 and 1994 was retrospectively reviewed utilizing univariate and multivariate statistical methods. RESULTS: With a median follow-up of 7.5 years, the overall freedom from relapse was 78% and 75% at 5 and 10 years, respectively. Of the total, 23 patients received radiation for gross disease because it was not resectable. Of these 23 patients, 7 sustained local recurrence, yielding a 31% actuarial relapse rate at 5 years. Radiation dose was the only significant determinant of disease control in this group. A dose of 50 Gy was associated with a 60% relapse rate, whereas higher doses yielded a 23% relapse rate (p < 0.05). The other 52 patients received radiation in conjunction with gross total resection of tumor. The 5- and 10-year relapse rates were 18% and 23%, respectively. No factor correlated significantly with disease outcome. There was no evidence that radiation doses exceeding 50 Gy improved outcome. Positive resection margins were not significantly deleterious in this group of irradiated patients. For all 75 patients, there was no evidence that radiation margins exceeding 5 cm beyond the tumor or surgical field improved local-regional control. Ultimately, 72 of the 75 patients were rendered disease-free, but 3 required extensive surgery (amputation, hemipelvectomy) to achieve this status. Significant radiation complications were seen in 13 patients. Radiation dose correlated with the incidence of complications. Doses of 56 Gy or less produced a 5% 15-year complication rate, compared to a 30% incidence with higher doses (p < 0.05). CONCLUSIONS: Radiation is an effective modality for desmoid tumors, either alone or as an adjuvant to resection. For patients with negative resection margins, postoperative radiation is not recommended. Patients with positive margins should almost always receive 50 Gy of postoperative radiation. Unresectable tumors should be irradiated to a dose of approximately 56 Gy, with a 75% expectation of local control.     

Women''s preferences for vaginal antimicrobial contraceptives. III. Choice of a formulation, applicator, and packaging

Local radiotherapy plays an important role in the palliative management of bone metastases. Different concepts of dose fractionation are in use. A judgement of the efficacy of these concepts should be based on their different palliative treatment endopoints. The efficacy of radiotherapy using published data can be analysed with respect to pain relief and re-establishment of bone integrity as treatment endopoints. Trials stratifying radiooncological techniques according to an optimization of quality of life are missing. Nevertheless, the rationale for individual treatment in daily work is based on systemic tumor extent, life expectancy, the kind of symptoms and the location of the metastasis in question. In patients with reduced live expectancy a remarkably high chance of pain relief (70%) could be achieved with single doses of 8 Gy. The latency period until pain relief is shorter with higher single doses. In case of recurrence of pain reirradiation with a single dose results in an equally high response rate. Patients with a solitary metastasis, patients with longer live expectancy and patients with pathological fractures should be treated with 'curative' doses, aimed to cause maximum tumor cell killing. Impaired bone stability in patients who are not suitable for surgical intervention requires orthetic supply. Apart from the effect of pain relief, remineralization is the important treatment goal for these patients. Conventional radiotherapy with doses of 40-50 Gy resulted in remineralization in 60-80% of the patients 4-8 weeks after irradiation. Remineralization could not be acceierated by short course fractionation courses.     

The fate of patients with locally advanced bladder cancer treated conservatively with neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy: 10-year experience

PURPOSE: We assess the results of bladder preservation for infiltrating bladder cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma. MATERIALS AND METHODS: From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease. RESULTS: Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases. CONCLUSIONS: Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.     

Preventive effects of an antiallergic drug, pemirolast potassium, on restenosis after percutaneous transluminal coronary angioplasty

PURPOSE: Radiosurgery is an effective treatment for cerebral arteriovenous malformations. We conducted the present study to investigate the feasibility and efficacy of gamma knife radiosurgery for dural arteriovenous fistulas (DAVFs) of the cavernous sinus. METHODS: Eighteen patients (12 women and six men; 29-75 years old [mean age, 55 years]) with DAVFs of the cavernous sinus (Barrow's type B:1, C:7, and D:10) treated by gamma knife radiosurgery were enrolled in the study. DAVFs were bilateral in six patients and unilateral in 12. Stereotactic X-ray angiography and MR imaging were performed for targeting the radiosurgery. Areas of arteriovenous communication targeted for irradiation were first outlined on the X-ray angiograms. The target regions were then transferred to and displayed on the MR images. Dose planning was based on findings on the integrated images. Prescribed maximum target doses were 22 to 38 Gy (mean, 28 Gy). The targets were covered by 50% to 90% isodose levels. Radiation doses to the surrounding optic apparatus were kept to less than 8 Gy. The patients were followed up with color Doppler sonography and MR imaging. When noninvasive imaging suggested obliteration, X-ray angiography was performed to verify the results. RESULTS: The DAVFs were totally obliterated in 12 (80%) of the 15 patients. In the other three, one was almost completely obliterated at 14 months and two were partially obliterated at 19 and 27 months, respectively, after radiosurgery. No complications or symptom worsening occurred during the follow-up period. CONCLUSION: Gamma knife radiosurgery is a feasible, effective, and safe treatment for DAVFs of the cavernous sinus. Integration of stereotactic X-ray angiography and MR imaging not only aids treatment efficacy but also protects the relevant vital structures, especially the optic apparatus, from the hazards of radiation.     

Radiotherapy of glioblastoma multiforme. Feasibility of increased fraction size and shortened overall treatment

PURPOSE: With regard to the poor prognosis of patients with glioblastoma multiforme, the aspect of life quality with a minimal treatment time becomes essential. The purpose of the present study is to evaluate whether the results of a radiotherapy schedule using increased single fractions applied over a shortened treatment time is feasible without compromising treatment efficiency or providing more side effects than a conventionally fractionated treatment. PATIENTS AND METHODS: A total of 38 patients (f = 21, m = 17, mean age 58 years) with histologically proven glioblastoma multiforme were irradiated after (partial) resection (n = 29) or stereotactic surgery (n = 9) with single doses of 3.5 Gy (ICRU) 5 fractions a week up to a total dose of 42 Gy following individual treatment planning. RESULTS: Median survival was 45.7 weeks, survival rate after 6 months was 80.9% and decreased to 34.2% after 12 months. Radiotherapy was tolerated without any important acute toxicity or any late side effects during the follow-up period. CONCLUSIONS: The increase of the dose per fraction using a fraction size of 3.5 Gy enhanced neither acute nor late toxicity. The survival rate compared well to those described in the literature. Thus the shortened treatment schedule seems as efficient as conventional radiotherapy. Moreover, it seems preferable with regard to quality of life.     

Stereotactic radiosurgery for recurrent malignant gliomas

PURPOSE: To evaluate the role of stereotactic radiosurgery in the management of recurrent malignant gliomas. PATIENTS AND METHODS: We treated 35 patients with large (median treatment volume, 28 cm3) recurrent tumors that had failed to respond to conventional treatment. Twenty-six patients (74%) had glioblastomas multiforme (GBM) and nine (26%) had anaplastic astrocytomas (AA). RESULTS: The mean time from diagnosis to radiosurgery was 10 months (range, 1 to 36), from radiosurgery to death, 8.0 months (range, 1 to 23). Twenty-one GBM (81%) and six AA (67%) patients have died. The actuarial survival time for all patients was 21 months from diagnosis and 8 months from radiosurgery. Twenty-two of 26 patients (85%) died of local or marginal failure, three (12%) of noncontiguous failure, and one (4%) of CSF dissemination. Age (P = .0405) was associated with improved survival on multivariate analysis, and age (P = .0110) and Karnofsky performance status (KPS) (P = .0285) on univariate analysis. Histology, treatment volume, and treatment dose were not significant variables by univariate analysis. Seven patients required surgical resection for increasing mass effect a mean of 4.0 months after radiosurgery, for an actuarial reoperation rate of 31%. Surgery did not significantly influence survival. At surgery, four patients had recurrent tumor, two had radiation necrosis, and one had both tumor and necrosis. The actuarial necrosis rate was 14% and the pathologic findings could have been predicted by the integrated logistic formula for developing symptomatic brain injury. CONCLUSION: Stereotactic radiosurgery appears to prolong survival for recurrent malignant gliomas and has a lower reoperative rate for symptomatic necrosis than does brachytherapy. Patterns of failure are similar for both of these techniques.     

Function-sparing surgery for desmoid tumors and other low-grade fibrosarcomas involving the brachial plexus

OBJECTIVE: Low-grade fibrosarcomas and desmoid tumors present a surgical challenge in that they have a strong tendency for local invasion, surgical margins are poorly delineated, and complete resections are difficult. Nowhere is this more evident than in those lesions involving the brachial plexus. We review our experience with these difficult lesions. METHODS: From a prospective database of 2900 patients admitted for treatment of sarcoma between 1982 and 1996, we identified 15 patients with involvement of the brachial plexus by a low-grade fibrosarcoma or desmoid tumor. All patients underwent resection, with 13 of 15 receiving adjuvant radiotherapy. The 15 patients had a mean age at initial operation of 47 years. The male-to-female ratio was 8:7. The mean follow-up period was 65 months (median, 53 mo). RESULTS: Gross total resection was achieved in 12 patients (80%), although 11 of these patients had positive surgical margins. Overall, 64% of the tumors have recurred locally. There were no distant metastases, and no patients died as a result of their disease. One patient died as a result of unrelated cancer. An assessment of the functional outcomes revealed seven patients with normal function or mild neurological deficits and eight who were suffering from significant weakness, debilitation, or chronic pain. One patient required forequarter amputation. CONCLUSION: Surgical resection plus postoperative radiotherapy is the treatment of choice for low-grade fibrosarcomas and desmoid tumors involving the brachial plexus. However, aggressive surgical management with the goal of achieving a gross total resection with negative histological margins can produce unnecessary morbidity. Preserving function should be a primary goal of the operations, although this will be associated with residual disease and will risk local recurrence but rarely death resulting from the disease.     

Radiotherapy of plantar heel spurs: indications, technique, clinical results at different dose concepts

BACKGROUND: In a retrospective study the efficacy of orthovoltage radiotherapy for refractory painful plantar heel spur was analyzed for 3 different radiation dose concepts. PATIENTS AND METHODS: From 1.1 1984 through 1.3.1994, 182 patients with refractory painful heel symptoms and radiologically proven plantar heel spur received radiotherapy. A total of 141 patients and 170 heels (due to double-sided symptoms) were completely documented in long-term follow-up. Clearly defined semi-quantitative criteria (9-point score) were used to analyze heel pain and ankle function prior to RT, 6 to 12 weeks post-radiation, and at last follow-up. The treatment outcome, i.e. (un)favourable response, of 3 radiation dose concepts were compared: Group A (n = 72 heels) received 12 Gy total radiation dose in 3 fractions per week and 2 series (6 x 1 Gy per series) separated by 6 weeks; group B (n = 98 heels) received 3 Gy total radiation dose in 10 fractions of 0.3 Gy (n = 50) or 5 Gy (10 x 0.5 Gy) (n = 48) with conventional fractionation in 1 series. RESULTS: Radiotherapy was very effective: at last follow-up 67% (group A) and 71% (group B) remained completely free of pain. The rate of "complete pain relief" (i.e. free of any pain symptoms) was not different between the 3 radiation concepts. However, significant differences were observed with regard to "incomplete or insufficient pain relief", i.e. a subjective pain relief of less than 80%, a delayed pain relief after more than 4 weeks or a relapse of pain symptoms in long-term follow-up. More favourable results were achieved in patients receiving 5 Gy or 12 Gy total dose, while patients with 3 Gy total dose had significantly worse results. Prognostic factors for "complete pain relief" were short duration of pain symptoms and acute pain symptoms prior to radiotherapy; with regard to "in-complete or insufficient pain relief" the total dose was found to be a prognostic parameter. CONCLUSIONS: Patients with refractory heel pain can yield a high response to radiotherapy even after failing various conventional treatments previously. Thus, radiotherapy should not be solely regarded as a last resort due to its low costs and high efficacy at low radiation doses.     

Exfoliative cytology for diagnosis of Helicobacter pylori]

From January 1988 through June 1996, 12 patients who had extrahepatic bile-duct cancer received preoperative radiotherapy at doses of 40.6 Gy to 58.4 Gy. At restaging, 1 patient was found to have liver metastases and the remaining 11 patients were taken to surgery. Nine patients underwent resection, and 8 of the 9 received intraoperative radiotherapy. Complications occurred in 4 patients, 3 of whom died postoperatively. The 2 patients who died of intraabdominal complications received both preoperative radiation doses of more than 55 Gy and intraoperative radiotherapy doses of 14 Gy or more. Histologic evidence of irradiation effects was present in all specimens. Irradiation effects on perineural invasion were observed in varying degrees. Two of the four patients who had marked irradiation effects on perineural invasion developed local recurrence, which was found at autopsy to have infiltrated the hepatic hilum without obstructing the hepatic ducts. One patient who had minimal irradiation effects on perineural invasion developed local recurrence with obstructing the hepatic ducts. Of the 2 patients who had positive margins, the patient with marked irradiation effects on perineural invasion survived 18 months, but the patient with slight irradiation effects on perineural invasion survived only 5 months. The high complication rate requires modification of this strategy. The propriety of combining preoperative radiotherapy with intraoperative radiotherapy as well as the radiation dose should be reinvestigated.     

Long-term outcomes after radiosurgery for acoustic neuromas

BACKGROUND: Stereotactic radiosurgery is the principal alternative to microsurgical resection for acoustic neuromas (vestibular schwannomas). The goals of radiosurgery are the long-term prevention of tumor growth, maintenance of neurologic function, and prevention of new neurologic deficits. Although acceptable short-term outcomes have been reported, long-term outcomes have not been well documented. METHODS: We evaluated 162 consecutive patients who underwent radiosurgery for acoustic neuromas between 1987 and 1992 by means of serial imaging tests, clinical evaluations, and a survey between 5 and 10 years after the procedure. The average dose of radiation to the tumor margin was 16 Gy, and the mean transverse diameter of the tumor was 22 mm (range, 8 to 39). Resection had been performed previously in 42 patients (26 percent); in 13 patients the tumor represented a recurrence of disease after a previous total resection. Facial function was normal in 76 percent of the patients before radiosurgery, and 20 percent had useful hearing. RESULTS: The rate of tumor control (with no resection required) was 98 percent. One hundred tumors (62 percent) became smaller, 53 (33 percent) remained unchanged in size, and 9 (6 percent) became slightly larger. Resection was performed in four patients (2 percent) within four years after radiosurgery. Normal facial function was preserved in 79 percent of the patients after five years (House-Brackmann grade 1), and normal trigeminal function was preserved in 73 percent. Fifty-one percent of the patients had no change in hearing ability. No new neurologic deficits appeared more than 28 months after radiosurgery. An outcomes questionnaire was returned by 115 patients (77 percent of the 149 patients still living). Fifty-four of these patients (47 percent) were employed at the time of radiosurgery, and 37 (69 percent) remained so. Radiosurgery was believed to have been successful by all 30 patients who had undergone surgery previously and by 81 (95 percent) of the 85 who had not. Thirty-six of the 115 patients (31 percent) described at least one complication, which resolved in 56 percent of those cases. CONCLUSIONS: Radiosurgery can provide long-term control of acoustic neuromas while preserving neurologic function.     

Late effects of radiotherapy on the neuroendocrine system

When the hypothalamic-pituitary axis (HPA) is included in the treatment field in children and adults, a variety of neuroendocrine disturbances are more common than has been appreciated in the past. Clinical damage to the pituitary and thyroid glands usually occurs months to years after treatment, and is preceded by a long subclinical phase. Primary brain tumors represent the largest group of malignant solid tumors in children. The survival rates of 50% reported in the literature are achieved at the expense of late occurring effects. Radiation-induced abnormalities are generally dose-dependent. Growth hormone deficiency and premature sexual development can occur at doses as low as 18 Gy in conventional fractionation, and is the most common neuroendocrine problem in children. In patients treated with > 40 Gy on the HPA, deficiency of gonadotropins, thyroid stimulating hormone, and adrenocorticotropin can be found. Following high-dose radiotherapy (> 50 Gy), hyperprolactinemia can be seen, especially among young women. Most neuroendocrine disturbances that develop as a result of HPA can be treated efficiently, provided that an early detection of these endocrine dysfunctions abnormalities is done.     

Evidence into practice, experimentation and quasi experimentation: are the methods up to the task?

PURPOSE: To assess the suitability of the cytokinesis block micronucleus assay as a biological dosimeter following in-vivo radiation using cancer patients undergoing radiotherapy. METHODS: Blood from 4 healthy donors was irradiated in vitro with gamma-rays and the dose response of induced micronuclei in binucleate lymphocytes following cytokinesis block was determined. Micronucleus frequency was ascertained before and at intervals during radiotherapy treatment in 6 patients with various tumors in the pelvic region. Equivalent whole body doses (physical doses) at these times were calculated from radiation treatment plans and cumulative dose volume histograms. RESULTS: Linear dose response relationships were found for induced micronucleus frequency in lymphocytes resulting from both in-vitro and in-vivo irradiation. Doses resulting from in-vivo irradiation (biological doses) were estimated by substitution of micronucleus frequency observed in radiotherapy patients into the dose response curve from in-vitro irradiation of blood. The relationship between the biologically estimated dose (BD) and the calculated equivalent whole body dose (PD) was BD = 0.868 (+/- 0.043)PD + 0.117 (+/- 0.075). CONCLUSION: The micronucleus assay appears to offer a reliable and consistent method for equivalent whole body radiation dose estimation, although our findings should be confirmed using lymphocytes from radiotherapy patients with tumors at anatomical sites other than the pelvis. Except at doses lower than about ).4 Gy, the method yields dose estimates acceptably close to "true" physically determined doses. The assay can be performed relatively rapidly and can be used as a "first line" biological dosimeter in situations where accidental exposure to relatively high radiation doses has occurred.     

The value of conventionally fractionated radiotherapy in the local treatment of HIV-related Kaposi's sarcoma

BACKGROUND: During the course of AIDS, 25 to 44% of homosexual patients infected with the human immunodeficiency virus develop Kaposi's sarcoma. Main manifestation is the skin. Response rates of 80 to 100% can be achieved with total dosage up to 50 Gy. Nevertheless, remissions can also be attained with 20 Gy of fractionated radiotherapy. As clinical data on low dose conventional fractionated radiotherapy are insufficient we analysed the response rates of an overall dose of 20 Gy in conventional fractionation. PATIENTS AND METHODS: From June 1991 to June 1993, 43 patients with 111 HIV-associated Kaposi's sarcoma of the skin or oral cavity were treated. Lesions were irradiated with 5 to 12 MeV electrons or 60Co gamma-rays. The fractionation scheme was 5 times 2 Gy/week for skin and endoral lesions with a total reference dosage of up to 20 Gy. Side effects were assessed during therapy and the therapeutic result 6 weeks after end of treatment. RESULTS: Thirty-eight out of 111 lesions were judged as complete response (CR) (34%), 61/111 as partial response (PR) (55%) and 12/111 were judged as no change (NC) (11%). Overall response (CR + PR) was 89%. Two patients with lesions of oral cavity suffered from RTOG grade-IV mucositis after 10 and 14 Gy. In 71/106 skin lesions (67%), radiation induced RTOG grade-1 reactions were observed. CONCLUSION: In patients with HIV associated Kaposi's sarcoma effective palliation can be achieved by means of radiotherapy with an overall dose of 20 Gy in conventional fractionation. Yet, the fraction of patients with complete responses is with 34 to 47% lower compared with doses above 20 Gy (66 to 100%). With reference to the reported data our results point to a dose-response relationship for Kaposi's sarcoma. Therefore higher total reference doses, e.g. 30 Gy with weekly 5 times 2 Gy or 24 Gy with 5 times 1.6 Gy for mucous lesions, respectively, are suggested as by this mean the complete response rate can be doubled.     

Stereotactic radiosurgery of angiographically occult vascular malformations: 14-year experience

OBJECTIVE: Radiosurgery is generally effective in obliterating true arteriovenous malformations, but less is known about its effects on angiographically occult vascular malformations (AOVMs). Since July 1983, 57 patients with surgically inaccessible AOVMs of the brain were treated using helium ion (47 patients) or linear accelerator (10 patients) radiosurgery. This study retrospectively evaluates the response of these AOVMs to treatment. METHODS: All patients presented with previous hemorrhage. The mean patient age was 35.6 years (range, 13-71 yr). The mean AOVM volume was 2.25 cm3 (range, 0.080-15.2 cm3), treated with a mean of 18.0 Gy equivalent (physical dose x relative biological effectiveness, which is 1.3 for helium ion Bragg peak) (range, 7.0-40 Gy equivalent). The Drake scale scores before treatment were as follows: excellent (25 patients), good (26 patients), and poor (6 patients). The mean follow-up period was 7.5 years (range, 9 mo-13.8 yr). RESULTS: Eighteen patients (32%) bled symptomatically (20 hemorrhages) after radiosurgery. Sixteen hemorrhages occurred within 36 months after radiosurgery (9.4% annual bleed rate; 16 hemorrhages/171 patient yr); 4 hemorrhages occurred more than 36 months after treatment (1.6% annual bleed rate; 4 hemorrhages/257 patient yr) (P < 0.001). Complications included symptomatic radiation edema (four patients, 7%), necrosis (one patient, 2%), and increased seizure frequency (one patient, 2%). Eight patients underwent surgical resection of their AOVMs 8 to 59 months after radiosurgery because of subsequent hemorrhage. The Drake scale scores after treatment were as follows: excellent (25 patients), good (24 patients), poor (3 patients), and dead (5 patients, 3 of whom died as a result of causes unrelated to the AOVMs or radiosurgery). CONCLUSION: Radiosurgery may be useful for AOVMs located in surgically inaccessible regions of the brain. A significant decrease in bleed rate exists more than 3 years after treatment compared with the bleed rate within 3 years of treatment. Because current neuroradiological techniques are not able to image obliterative response in these slow-flow vascular lesions, longer term clinical follow-up is required.