A noninvasive eye fixation monitoring system for CyberKnife radiotherapy of choroidal and orbital tumors.

A new noninvasive monitoring system for fixing the eye has been developed to treat orbital and choroidal tumors with CyberKnife-based radiotherapy. This device monitors the eye during CT/MRI scanning and during treatment. The results of this study demonstrate the feasibility of the fixation light system for CyberKnife-based treatments of orbital and choroidal tumors and supports the idea that larger choroidal melanomas and choroidal metastases could be treated with CyberKnife without implanting fiducial markers.

Delayed traumatic midbrain syrinx. Clinical, pathologic, and electrophysiologic features.

Seven months following severe crushing closed-head trauma with initial excellent recovery, neurologic deficits referable to the right mesencephalon abruptly developed in a 28-year-old man. Computed tomography demonstrated a cystic midbrain lesion with apparent communication with the aqueduct (later confirmed at autopsy). Brain-stem auditory evoked potentials after the clinical deterioration showed depression of amplitude of wave V, compared with predeficit records, only when the ear contralateral to the brain-stem lesion was stimulated.

Radiation therapy for benign central nervous system disease.

The most common indication for the use of radiation therapy in the treatment of benign central nervous system disease is for the treatment of benign brain tumors, such as meningioma, pituitary adenoma, acoustic neuroma, arteriovenous malformation, and craniopharyngioma. Other less common benign intracranial tumors treated with radiation include chordoma, pilocytic astrocytoma, pineocytoma, choroid-plexus papilloma, hemangioblastoma, and temporal bone chemodectomas. Benign conditions, such as histiocytosis X, trigeminal neuralgia, and epilepsy, are also amenable to radiation treatment. There have also been reports of radiosurgery being used for the treatment of movement disorders and psychiatric disturbances, such as obsessive-compulsive and anxiety disorders. For benign brain tumors, radiation therapy as either primary or adjuvant therapy plays an integral role in improving local control. In the treatment of trigeminal neuralgia, epilepsy, tremor, and some psychiatric disturbances, radiosurgery may help ameliorate or eliminate some symptoms. Patients with benign central nervous system disease are expected to live a long time. As such, treatment should be highly conformal and based on three-dimensional planning using magnetic resonance imaging, computed tomography, or both. It is critical that damage to normal brain be minimized.

Estimation of complications for linear accelerator radiosurgery with the integrated logistic formula.

Radiosurgery techniques permit high doses of single fraction irradiation to be administered to small volumes of tumor with relative sparing of surrounding brain tissue. The tolerance of surrounding normal brain tissue to dose distributions from linear accelerator radiosurgery with different collimator sizes is an important factor that must be estimated by anyone using these treatment techniques. The exponential and linear quadratic versions of the integrated logistic formula were used to estimate the probability of brain necrosis at different doses for radiosurgical dose distributions administered by a 6 MV linear accelerator with a 5 arc technique for collimator sizes from 12.5 to 30 mm in diameter. Dose-volume isoeffect curves for a 3% risk of brain necrosis from linear accelerator radiosurgery were then calculated. These curves approximate those calculated for gamma knife radiosurgery and a published 1% dose-volume isoeffect line predicted for proton beam irradiation. Similar dose-volume isoeffect curves were calculated for single fraction radiosurgery boosts administered after 30 Gy of whole brain irradiation in 12 fractions. The integrated logistic formula appears to be a useful tool for estimating tolerance and providing guidelines for prescribing radiation doses for linear accelerator radiosurgery.

The effect of setup uncertainties on the radiobiological advantage of fractionation in stereotaxic radiotherapy.

PURPOSE: There may be radiobiological advantages in administering stereotaxic radiation treatment in multiple fractions instead of by a single irradiation. However, a larger planning target volume may be required for fractionated stereotaxic radiotherapy than for a single session treatment, if decreased geometrical precision and increased setup uncertainty are associated with multiple-fraction treatments. This factor may partially offset the radiobiological gain. The purpose of this study is to estimate the potential therapeutic gain of fractionated treatments for brain tumors, and to assess the effect of increased setup uncertainty on the potential gain. METHODS AND MATERIALS: The concept of biologically effective dose (BED), based on the linear quadratic (LQ) model, was used to quantify the therapeutic efficacy of the respective treatment schema. Therapeutic gain (TG) was defined as the ratio of tumor BEDs, for multiple fractions and single treatment, respectively, for the same normal brain BED. To include the effect of increased planning volume in fractionated treatment, a power-law relationship was assumed for the volume dependence of prescription dose, and the TG was recalculated using the "volume-adjusted" doses. RESULTS: The therapeutic gain for fractionated treatment increases with fraction number, and is smaller for larger single treatment doses. For example, in going from 1 to 10 fractions, the TG is 1.40, 1.32, or 1.27 for single treatment dose of 20, 30, or 40 Gy, respectively. Also, the TG is more significant for the initial few fractions. The benefit of fractionation is diminished if larger planning volume is needed for multiple fraction treatments. For example, the above TG are reduced to 1.19, 1.11, or 1.06, if a 2 cm planning target volume in single fraction treatment is enlarged to 2.3 cm in fractionated treatment. CONCLUSION: Consideration of the therapeutic gain with fractionation should include estimates of setup uncertainty for multiple-fraction treatments, relative to that of single fraction radiosurgery.

Hyperfractionated irradiation for adults with brainstem gliomas.

Hyperfractionated irradiation appears to have improved survival for pediatric patients with brainstem gliomas. However, the efficacy and safety of this technique are less well established for adults with brainstem tumors. In 1984 the UCSF Department of Radiation Oncology began treating adults with brainstem gliomas using 100 cGy fractions given twice daily to total doses ranging between 6600-7800 cGy (median dose 7200 cGy). By the end of 1989, a total of 14 patients had been irradiated with follow-up times for surviving patients ranging between 4-69 months (median follow-up 33 months). Tumor histologies included five moderately anaplastic astrocytomas, one highly anaplastic astrocytoma, and eight which were unbiopsied. At the time of this analysis, six patients had failed locally, with five dying as a result of recurrent tumor. There were no deaths caused by complications or intercurrent illness. The 3-year actuarial survival rate was 59%, with a corresponding 3-year actuarial local control rate of 48%. The projected median survival was in excess of 5 years, whereas the actuarial median time to progression was 31 months (134 weeks). The treatments were well tolerated: the mean pretreatment Karnofsky Performance Status was 74% (range 60-90%); at the end of treatment the mean KPS was 78% (range 60-100%). In terms of neurologic status, six patients improved by the end of treatment, seven were stable, and one experienced only minor deterioration without change in KPS. There were no significant long-term complications (specifically, no instances of either radiation brain necrosis or myelitis). Seven patients required prolonged steroid administration after completing radiotherapy; six of these eventually recurred locally. These results appear to be substantially better than those achieved using conventional radiotherapy regimens, and suggest that this technique merits further investigation.

Evaluation of radiosurgery techniques with cumulative dose volume histograms in linac-based stereotactic external beam irradiation.

Radiosurgery at UCSF is performed with a 6-MV linear accelerator with tertiary collimation for improved small field definition. The dose delivery to the target relative to normal tissue is influenced by the number of arcs, the arc geometry, field size, and beam energy. The impact of arc number, arc geometry, and field size on the dose distribution from 6-MV X rays in a 16 cm spherical phantom has been evaluated through the use of cumulative dose volume histograms. Dose volume histograms were calculated for a) 1-5 and 10 arcs, and b) collimator sizes of 1.25, 2.0, and 3.0 cm. Differences between techniques were found at the 5-10% level for field sizes from 1.25 to 2.0 cm. It was shown that the finite dimension of the sphere and, by extension, head diminishes the differences between techniques for the larger field sizes. The effect of treating with two isocenters is also analyzed and an approach for improving the dose distribution is presented.

Neuropsychological sequelae of medulloblastoma in adults.

PURPOSE: To investigate the neuropsychological consequences of medulloblastoma in adults. METHODS: Patients 18 years of age or older who had medulloblastoma and at least 3 years of disease-free survival were eligible. A battery of tests was conducted to assess global intellectual functioning, verbal ability, visuospatial ability, memory, reasoning, and academic proficiency. For the verbal memory performance, each patient was matched with two normal controls selected on the basis of age, sex, and level of education. RESULTS: Review of the Neuro-Oncology database revealed 24 patients eligible for the study. Of these, 10 patients (6 good-risk and 4 poor-risk) agreed to participate; 7 patients were lost to follow-up; 5 lived too far away to come to the testing site, and 2 refused testing. There were four men and six women; their mean age was 36.5 years at testing and 29.9 years at surgical diagnosis. Mean dose of whole brain radiation was 34.5 Gy. Mean interval between diagnosis and testing was 79.1 months. Test results demonstrated below average intelligence quotients (mean intelligence quotient 90.2; range 67-103) and specific deficits in memory, reasoning, visuospatial ability, and arithmetic. CONCLUSION: Adults with medulloblastoma in a prolonged disease-free status may suffer significant cognitive deficits. We recommend further controlled, prospective studies to evaluate cognitive outcomes in this patient population in the hope that interventional strategies could be developed, or treatment modified to minimize such toxicities.

Hyperfractionated radiation therapy for gliomas of the brainstem in children and in adults.

Between February 1984 and September 1990, 60 patients with brainstem gliomas were treated with hyperfractionated radiotherapy in the Department of Radiation Oncology at the University of California, San Francisco. Forty-one children (< or = 18 years) and 19 adults were treated with 100 cGy twice daily with 4-8 hr between doses. Thirty-one patients (21 children and 10 adults) received total doses of 66-72 Gy and 29 patients (20 children and nine adults) received 74-78 Gy. Median follow-up was 208 weeks for all patients (214 weeks for children, 157 weeks for adults). Twenty-three patients (14 children and nine adults) were alive at the time of analysis, surviving 59-359 weeks following treatment. Median actuarial survival was 73.6 weeks overall (72 weeks for children, 190 weeks for adults; p = 0.43). Survival at 12 and 24 months was 65% and 38%, respectively (63% and 32%, for children; 68% and 53% for adults). All patients had pretreatment magnetic resonance imaging by which tumors were classified as either focal or diffuse. No significant pretreatment prognostic factors for adults were identified. In children, significant favorable prognostic factors on univariate analysis were older age (p = 0.001), tumor location in thalamus or midbrain (p = 0.002), focal appearance on MRI scan (p < 0.001) and duration of symptoms > 2 months prior to treatment (p < 0.001). Thirty-five patients had tumor biopsies, leading to a diagnosis in 33 (22 children and 11 adults). Children with moderately anaplastic astrocytomas survived significantly longer than those with glioblastoma multiforme or unbiopsied tumors (p < 0.001). Only duration of symptoms > 2 months remained significant as a favorable prognostic indicator for children on multivariate analysis (p < 0.001). Survival was not significantly different for patients receiving < or = 72 Gy and those receiving > 72 Gy (p = 0.18). No subgroup of patients showed significantly better survival with the higher dose. These findings indicate that hyperfractionated radiotherapy is effective treatment for adults and a subgroup of better prognosis children with brainstem gliomas. There is a subgroup of pediatric patients with extremely poor prognosis for whom even this aggressive treatment does little to extend survival. We conclude that there is no benefit to increasing total dose above 72 Gy for any of the groups analyzed.

Re-irradiation of pituitary adenoma.

Fifteen patients initially irradiated for pituitary adenoma were subsequently treated with a second course of radiotherapy at the University of California at San Francisco between 1961 and 1989. The re-irradiation followed surgery in all but two cases. The median time to recurrence was 9 years (range 2-17) and median follow-up after the second course of radiotherapy was 10 years (range 1-30). The median initial radiation dose was 4084 cGy; that at recurrence was 4200 cGy. Local control has been maintained in 12 patients. One failed locally with a benign adenoma that was surgically salvaged. Two developed pituitary carcinomas which were poorly controlled. Of the patients who presented with visual abnormalities at the time of recurrence, 50% improved and the remainder stabilized after re-irradiation. There are no long-term visual complications. Hypopituitarism was present in nine patients prior to the second course of radiotherapy and developed in the remaining six patients after re-irradiation. Temporal lobe injury was seen in two patients. Careful analysis of each patient's pituitary and temporal lobe doses, intervals between treatments, treatment volume, neurets, relative decay factors, absolute decay factors, TDF and modified LQF values, and dose-volume relationships, revealed no correlation with complication or likelihood of local control. Repeat radiotherapy for recurrent pituitary adenoma with the doses used in these patients appears to carry acceptable risk with good local control.

Precision radiation therapy for optic nerve sheath meningiomas.

A more precise radiation therapy technique to treat unilateral optic nerve sheath meningioma is presented. It uses an immobilization device to align the ipsilateral optic nerve with a vertical axis and employs three small half-beam blocked fields to deliver radiation to a small conformal volume, thereby reducing the dose to the optic chiasm and the contralateral optic nerve. Three patients were successfully treated with this technique, and a fourth patient with optic nerve glioma was also treated in a similar fashion and was included in this study. The new technique irradiates a much smaller volume of tissue to high dose levels: 58 cm3 is irradiated to the 80% isodose level and only 18 cm3 to the 95% level. In contrast, the opposed lateral technique irradiates 171 and 73 cm3 to these levels, respectively. Thus, a considerable reduction in the volume of normal tissue irradiated was accomplished. Doses to the pituitary and contralateral optic nerve were 4% of the treatment dose for the new technique, whereas these doses were 40% and 100% for opposed laterals and 10% and 3% for wedged pair, respectively. The average setup error for this technique was very small, 50% of the setups measured were less than 1 mm off, and 92.5% were less than 3 mm off. However, for the conventional setups without a mask, only 21% of the setups were less than 1 mm off and 55% less than 3 mm off. We recommend this technique for localized unilateral optic nerve sheath meningioma and other optic nerve lesions that may require radiation therapy.

Current radiosurgery practice: results of an ASTRO survey. Task Force on Stereotactic Radiosurgery, American Society for Therapeutic Radiology and Oncology.

PURPOSE: Although there is increasing interest in radiosurgery, little quantitative data regarding current patterns of radiosurgery practice are available. We developed a radiosurgery questionnaire to obtain information on radiosurgery practice. METHODS AND MATERIALS: We distributed the questionnaire to the entire membership of the American Society of Therapeutic Radiology and Oncology in early 1993. Responses were obtained from 74 facilities that practice radiosurgery, corresponding to over 6000 treatments carried out since 1983 by 135 radiation oncologists and 130 physicists. RESULTS: Most respondents were found to work within a multidisciplinary team, consisting of the following specialists (average hours devoted per patient on day of treatment in parentheses): radiation oncologist (3.8), neurosurgeon (3.2), physicist (6.1), radiologist (0.7), nurse (2.7), other (3.0). On average, neurosurgeons and nurses who perform Gamma Knife radiosurgery devote significantly more time-per-patient on the day of treatment than their peers who perform linac radiosurgery. On average, less experienced radiation oncologists and physicists (< or = 24 months experience, or < or = 50 patients treated) devote significantly more time-per-patient on the day of treatment than their more experienced peers. Although there are many more linac radiosurgery facilities than Gamma Knife facilities, on average the number of patients treated per month per facility is significantly larger at the latter. On average, follow-up responsibilities are nearly equally shared by radiation oncologists and neurosurgeons, except at Gamma Knife facilities, where neurosurgeons assume a larger percentage of follow-up responsibility. The percentages of patients treated at linac facilities for metastases or primary CNS malignancy are larger than the corresponding percentages at Gamma Knife facilities; the opposite is true for arteriovenous malformation, acoustic neuroma, and meningioma. CONCLUSION: Current radiosurgery practice usually involves a team approach, with participation of specialists from radiation oncology, neurosurgery, physics, radiology, and nursing. The average number of M.D. and Ph.D. hours required per treatment on the day of radiosurgery is high.

Neon heavy charged particle radiotherapy of glioblastoma of the brain.

PURPOSE: High-linear energy transfer (LET) radiation beams have potential applications in the treatment of glioblastoma, but have not yet demonstrated significant improvement in results. However, some patients have had local control of glioblastoma with high-LET irradiations such as neutrons and heavy charged particles. METHODS AND MATERIALS: In this collaborative study, 15 patients were entered into a randomized protocol comparing two dose levels of 20 and 25 Gy in 4 weeks of neon ion irradiation. This trial was intended to determine the optimal neon dose in terms of survival and effects of radiation. RESULTS: Fourteen patients were evaluable with no significant differences in median survival (13 and 14 months; p = NS) or median time to failure (7 and 9 months; p = NS) between the two dose arms. Three patients died of nontumor-related causes, of whom one (who died 19 months posttreatment) had autopsy confirmation of no tumor on pathological exam. The other two patients had stable magnetic resonance imaging scans at 6 and 22 months posttreatment. CONCLUSION: Although the results did not demonstrate the optimal high-LET dose level, there is an intriguing effect in that two patients had control of glioblastoma until death at 19 and 22 months. This suggests that better conformation of the high-LET dose to the tumor with neutron capture therapy or dynamic conformal heavy charged particle therapy might control glioblastoma while minimizing brain damage from radiation.

The treatment of brain stem and thalamic gliomas with 78 Gy of hyperfractionated radiation therapy.

PURPOSE: To see whether increasing the dose of hyperfractionated radiation therapy from 72 to 78 Gy would increase survival time in patients with gliomas, particularly those with brain stem or thalamic tumors. METHODS: Seventy-eight patients with a clinical and radiographic diagnosis of a brain stem or thalamic glioma were enrolled in a trial to receive 78 Gy (1.0 Gy twice a day). Six patients with disease in other sites were also treated. The initial response to therapy was determined by comparing pretreatment magnetic resonance images and neurological examinations with those obtained within 2 weeks of completing therapy; subsequent responses were determined from bimonthly follow-up images. Time-to-tumor progression was measured from the date radiation therapy began until the date of documented radiographic or clinical progression. Survival time was measured from the date radiation therapy began until the date of death. Cox proportional hazards analysis was used to estimate the effects of specific variables on survival. RESULTS: Of 81 evaluable patients, 68 received > or = 76 Gy, 10 received between 70 and 75 Gy, and 3 received between 60 and 68 Gy. The overall response or stabilization rate was 70.4%. Tumor size decreased in 30.8% of patients; 39.5% had stable disease, and 29.6% had immediate progression. The median survival time was 12.7 months (16.1 months for adults and 10.8 months for children). The median time to tumor progression was 9.0 months (11.4 months for adults and 8.4 months for children). A duration of symptoms < or = 2 months and a diffuse lesion were each associated with shorter survival and progression times. CONCLUSIONS: For patients with brain stem or thalamic gliomas, increasing the dose of radiation therapy from 72 to 78 Gy did not significantly improve survival. Different treatment strategies are clearly needed.

Medulloblastoma in adults.

PURPOSE: To examine the relationship between extent of disease and outcome in adults with medulloblastoma. METHODS AND MATERIALS: We reviewed the records of all patients over 15 years old with newly diagnosed or recurrent medulloblastoma treated by or referred to the University of California, San Francisco, and recorded demographic characteristics, clinical symptoms, radiographic findings, extent of resection, staging, myelography, computerized tomography (CT) scans or magnetic resonance (MR) images of the spine, histopathological assessment, treatment received, treatment response, recurrence patterns, and survival duration. RESULTS: A total of 47 patients were identified, 26 of whom were designated "poor-risk" because they had < 75% removal of tumor, metastatic disease, or brain-stem or leptomeningeal invasion. All patients had radiation therapy; 32 had adjuvant chemotherapy. Twenty-two patients (47%) died of tumor progression, 19 are progression-free, and 6 are alive with disease. The median survival time was 282 weeks in poor-risk patients and has not been reached in good-risk patients. Overall and disease-free 5-year survival rates differed significantly between the two groups (81% vs. 54%, p = 0.03 and 58% vs. 38%, p = 0.05, respectively). Tumors most often recurred in the posterior fossa. The median survival time from recurrence was 77 weeks (range 44 to 89 weeks). CONCLUSION: These findings are similar to those reported for children. Therefore, staging and treatment in adults should be approached the same way as in children: staging should include cerebrospinal fluid assessment and spinal imaging. Treatment should be based on staging, and should include craniospinal irradiation; additional chemotherapy should probably be reserved for poor-risk patients.

Radiation therapy for primary intracranial germ-cell tumors.

PURPOSE: To evaluate the diagnosis, therapy, and survival of patients with intracranial germ-cell tumors. To define the role of prophylactic craniospinal irradiation and chemotherapy necessary to impact on survival. METHODS AND MATERIALS: Forty-eight patients with surgically confirmed or suspected primary intracranial germ-cell tumors treated at UCSF between 1968-1990 were reviewed. Thirty-four patients had a pathologic diagnosis, including 24 germinomas, 3 malignant teratomas, 2 choriocarcinomas, 1 embryonal carcinoma, 1 endodermal sinus tumor, and 3 mixed tumors. Information obtained included histology, location, cerebrospinal fluid (CSF) cytology, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (B-HCG), metastatic evaluation, radiation details, survival, and sites of failure. Minimum follow-up time was 2 years and ranged to a maximum of 24 years, with a median of 8 years. RESULTS: Median age at diagnosis was 16 years with 36 males and 12 females. Ten of 32 patients had elevated B-HCG at diagnosis; 6 of 29 had elevations of AFP. Cerebrospinal fluid cytology was negative in 35 of 36 patients evaluated; myelography or spinal MRI was positive in only 1 of 31 patients studied. Five-year actuarial disease-free survival after irradiation was 91% for germinomas, 63% for unbiopsied tumors, and 60% for nongerminoma germ-cell tumors with doses of 50-54 Gy to the local tumor site with or without whole-brain or whole-ventricular irradiation. Routine prophylactic cranio-spinal axis irradiation was not given with a spinal only failure rate of 2%. Eleven of 48 patients have expired, with an actuarial 5-year survival rate of 100% for germinomas, 79% for nonbiopsied tumors, and 80% for nongerminoma germ-cell tumors. CONCLUSION: With complete diagnostic craniospinal evaluation, spinal irradiation is not necessary. Cure rates for germinomas are excellent with irradiation alone. Multidrug chemotherapy is necessary with irradiation for nongerminoma germ-cell tumors. Histology is the most important prognostic factor; therefore, all patients should have surgical conformation of their diagnosis so that appropriate treatment can be given.

Reirradiation of primary CNS tumors.

PURPOSE: Primary central nervous system (CNS) tumors are seldom reirradiated due to toxicity concerns and sparse clinical data regarding efficacy. METHODS AND MATERIALS: We retrospectively reviewed 34 patients with primary brain tumors retreated with fractionated external beam irradiation at the University of California, San Francisco from 1977-1993. Tumors included 15 medulloblastomas, 10 high-grade gliomas, 7 low-grade gliomas, and 2 meningiomas. RESULTS: Initial course of radiation was radical in intent for all patients. Median age at initial diagnosis was 19.8 years (range: 3.6-67). Median interval between radiation courses was 16.3 months (range: 3.8-166). Median Karnofsky Performance Status (KPS) prior to reirradiation was 80 (range: 40-100). Reirradiation volumes overlapped previous treatment in 30 patients and were nonoverlapping in 4 patients. Fractionation schemes used were hyperfractionated in 17, conventionally fractionated in 9, and hypofractionated in 8. Cumulative maximum overlap dose within the CNS ranged from 43.2-111 Gy (median: 79.7 Gy). Retreatment was completed as planned in 27 out of 34 patients and modified or aborted in 7 (four tumor progression on retreatment, three patient request). As measured from the time of retreatment median progression free and overall survival was 3.3 and 8.3 months. Clinical and radiographic indices were stabilized or improved in about half of patients evaluable at a median of 3 months postretreatment. Complications (early or late) potentially attributable to retreatment were noted in 10 of 34 (29%) of patients. Overt necrosis was noted in 3 of 34 (9%) of patients and the actuarial risk of necrosis was 22% at 1 year following retreatment. CONCLUSIONS: Reirradiation of primary central nervous system tumors was associated with only modest palliative and survival benefits in this retrospective review. Difficulties separating toxicity due to retreatment vs. tumor progression and limited patient survival following retreatment preclude definite conclusions regarding the safety of this practice.

Relationship between pattern of enhancement and local control of brain metastases after radiosurgery.

PURPOSE: A desired goal in the radiosurgery (RS) of brain metastases is improved local control. Our earlier retrospective review identified pattern of enhancement on day-of-treatment imaging as a prognostic indicator for freedom from progression (FFP) after RS in 219 brain metastases. The current study was performed to corroborate this preliminary finding. METHODS AND MATERIALS: Records and imaging studies of patients treated with RS from 1991 to 1997 were reviewed. Each metastasis was categorized as homogeneously-, heterogeneously-, or ring-enhancing. Kaplan-Meier FFP was calculated from the date of RS to the first imaging showing tumor progression. Univariate and multivariate analyses were performed using Cox proportional hazard models stratified by primary site and type of RS (alone, as a boost, or for recurrence). RESULTS: Of 682 lesions in 258 patients, 518 lesions in 193 patients were evaluable. Pattern of enhancement was homogeneous in 59%, heterogeneous in 32%, and ring-like in 8% of lesions. One-year FFP probabilities for homogeneously-, heterogeneously-, and ring-enhancing lesions were 90% (95% confidence interval, 84-93%), 76% (64-84%), and 57% (35-74%), respectively. The p-value for pattern of enhancement from the stratified multivariate analysis was 0.019 adjusting for RS dose and treatment period (1991-1994 vs. 1995-1997). Similar results were achieved adjusting for tumor volume instead of RS dose. CONCLUSION: Pattern of enhancement is confirmed as a significant prognostic factor for FFP of brain metastases treated with RS, independent of dose and volume. A possible explanation is radioresistance of hypoxic tumor cells associated with necrotic regions, suggesting future investigations with radiosensitizers, hypoxic cell sensitizers, or strategies to improve tumor oxygenation.

Pattern of recurrence of medulloblastoma after low-dose craniospinal radiotherapy.

PURPOSE: We retrospectively evaluated relapse of medulloblastoma after low- or high-dose craniospinal radiotherapy, and after conventional or hyperfractionated posterior fossa irradiation. METHODS AND MATERIALS: Ninety-two pediatric patients were treated postoperatively since 1970 at the University of California, San Francisco. Until 1989, we employed conventional fractionation with low (< or = 30 Gy) or high-dose craniospinal fields and low-dose (< or = 56 Gy) posterior fossa boosts. Recently, hyperfractionation delivered low- or high-dose to the craniospinal axis and high-dose to the posterior fossa. Most patients treated after 1979 received chemotherapy. RESULTS: Median follow-up was 70 months. Five-year disease-free survival was 36% (22% for poor-risk vs. 59% for good-risk patients). Five-year overall survival was 52% (43% for poor vs. 68% for good-risk). Neither the dose to the posterior fossa nor the craniospinal axis was statistically related to recurrence. Failure in the posterior fossa occurred despite boosts greater than 56 Gy. Females, over the age of 6 years, had significantly better relapse-free survival than males of the same age. Six of the 54 patients who relapsed were long-term survivors. CONCLUSIONS: Low-dose craniospinal radiotherapy, where the majority of patients received chemotherapy, was not associated with increased failure. High-dose posterior fossa hyperfractionation did not improve control. Long-term survival was noted in a number of patients after relapse. We recommend 60 Gy or greater with conventional fractions to the primary area, and continued study of low-dose craniospinal irradiation with adjuvant chemotherapy.

Survival and quality of life after interstitial implantation of removable high-activity iodine-125 sources for the treatment of patients with recurrent malignant gliomas.

Between January 1980 and January 1988, 95 evaluable patients with recurrent, unifocal, supratentorial malignant gliomas were reirradiated with high-activity iodine-125 sources implanted directly into tumor in afterloaded, removable catheters using computerized tomography-directed stereotaxy. A tumor dose of 5270-15,000 cGy was delivered at a maximum distance of 0.5 cm from the rim of the contrast-enhancing mass seen on CT scans. The median survival for the 50 patients with anaplastic astrocytoma was 81 weeks and for 45 patients with glioblastoma multiforme it was 54 weeks. The 18- and 36-month survival rates for patients with anaplastic astrocytoma were 46% and 28%, respectively; the 18- and 36-month survival rates for patients with glioblastoma multiforme were 22% and 8%, respectively. Because of clinical deterioration, increasing steroid dependency, and increasing mass effect at the implantation site seen on CT scans, necrotic tissue was excised from 47 patients (49%) at craniotomy; in some patients, tumor was mixed with necrotic tissue. The survival of reoperated patients was significantly longer compared with patients who did not undergo this procedure. Serial determination of the Karnofsky Performance Score (KPS) showed that there was no significant deterioration for the group as a whole during the 6 months immediately after implantation. At 18 months, 33 of the patients were alive; KPS ranged between 50 to 90 (mean 79) and 67% were steroid dependent. At 36 months, 18 patients were alive; 17 patients were evaluable with KPS that ranged between 40 to 90 (mean 76) and 53% were steroid dependent. Eleven of the 17 evaluable long-term survivors had a KPS of 80 or higher with a mean of 87. Interstitial brachytherapy may provide long-term survival in selected patients with recurrent malignant gliomas who have been irradiated previously with conventional teletherapy. The quality of life in the majority of long-term survivors appears to be quite satisfactory. Further attempts to control tumor growth using this modality appear to be warranted.