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The treatment of acoustic neuromas (AN) usually involves surgical excision or stereotactic radiosurgery. However, for large AN (mean diameter > 3 cm), stereotactic radiosurgery is rarely used, leaving patients with limited noninvasive treatment options. Recently, the use of fractionated stereotactic radiotherapy (FSRT) has been effective in treating small to medium-sized AN. We present a patient with a large AN treated with FSRT. The patient was a 43-year-old man presenting with imbalance, tinnitus, vertigo, and right-sided hearing decline associated with vomiting and hydrocephalus. Magnetic resonance (MR) imaging revealed a large, 3.8-cm, right cerebellopontine-angle tumor compressing the fourth ventricle. Following right frontal ventriculoperitoneal shunt placement, the patient underwent FSRT for treatment of the tumor. Using the Radionics X-Knife 4.0 3D treatment planning system, a total of 54 Gy was delivered in 1.8-Gy daily fractions with the prescription isodose line of 90%. Treatments were delivered using a dedicated Varian 6/100 linear accelerator, and head immobilization was achieved with the Gill-Thomas-Cosman relocatable stereotactic frame. The patient was subsequently evaluated with serial contrast-enhanced MR imaging. Following FSRT, local control (defined as the absence of tumor progression) was achieved, and treatment was well tolerated. There was no hearing-related, trigeminal, or facial-nerve morbidity following FSRT at 63-month follow-up. Treating a patient with a large AN with FSRT resulted in local tumor control, with no trigeminal nerve, facial nerve, or hearing-related morbidity. These results support FSRT as a potential noninvasive treatment modality for AN some would consider too large for single-fraction stereotactic radiosurgery (SRS).

Lung cancer is a major cause of cancer death worldwide and is becoming an increasing problem in developing countries. It is important that, in countries where health care resources are limited, these resources are used most effectively and cost-effectively. The authors, with the support of the International Atomic Energy Agency, drew on existing evidence-based clinical guidelines, published systematic reviews and meta-analyses, as well as recent research publications, to summarise the current evidence and to make broad recommendations on the non-surgical treatment of patients with lung cancer. Tables were constructed which summarise the different treatment options for specific groups of patients, the increase in resource use for and the likely additional clinical benefit from each option. These tables can be used to assess the cost-effectiveness and appropriateness of different interventions in a particular health care system and to develop local clinical guidelines.

The aim of this study is to evaluate the efficacy of stereotactic radiotherapy boost (SRB) in patients with glioblastoma multiforme (GBM) by comparing two different regimens, single dose or fractionated treatment. Between December 1994 and January 2000, 24 patients with GBM were treated with SRB in conjunction with external beam radiotherapy (EBRT). Fourteen patients (58%) were treated with stereotactic radiosurgery (SRS) and 10 patients (42%) with fractionated stereotactic radiotherapy (FSRT). Median interval between EBRT and SRS or FSRT was 1.4 months (range −0.4–3.9 months). Actuarial survival rates of the entire 24 patients at one and two years following SRB were 63% and 34% respectively, with median survival time of 16 months. Variables predicting survival were age, extent of surgery, re-operation and the RTOG (Radiation Therapy Oncology Group) classes based on recursive partitioning analysis (RPA). In comparison to historical controls, improved survival benefit after SRB was observed. The median survival times for the RTOG classes 4, 5, and 6 were 28.3, 10.3, and 6.0 months following EBRT+SRB, respectively. Expected values for these classes after EBRT are 11.1, 8.9, and 4.6 months, respectively. This improvement in survival was seen predominantly for the RTOG class 4. There was no difference in survival between SRS and FSRT treated groups. Late complications developed in 4 patients in the SRS group and 1 patients in the FSRT group. Our retrospective data suggest that SRB in conjunction with EBRT may improve survival in patients with GBM with median survival time of 16 months, when compared to historical controls of the RTOG data following EBRT. The addition of SRB appeared to improve the median survival most demonstrably in RTOG RPA class 4 patients. SRS and FSRT are equally effective with similar median survival, but potentially less late complications associated with FSRT. Since this is a nonrandomized study, further investigation is needed to confirm this and to determine an optimal dose/fractionation scheme.

Various immunotoxins have been developed for the treatment of cancer. The toxin is internalized by target cells through cell-surface receptors, and it is essential for these receptors to be expressed for the immunotoxin to have specific anti-tumor activity. Radiation therapy is one of the main treatment modalities for primary malignant brain tumors. The purpose of this study was to determine whether radiation influences the expression of cell-surface receptors. Cells of one human medulloblastoma (Daoy) and two glioblastoma (U373-MG and T98-G) cell lines were tested by exposing the cells to a single dose of 5 Gy gamma rays. Expression of transferrin receptors, type-1 insulin-like growth factor receptors (IGF1R), and interleukin 4 receptors (IL4R) was measured by flow cytometry analysis on unirradiated cells and on cells 3 to 120 h after irradiation. In Daoy cells, the absolute expression index of transferrin receptors increased during the 24 h after irradiation with the greatest change of 26% above control at 9 h. The absolute expression index of IGF1R increased 26.5% above control at 12 h. The absolute expression index of IL4R decreased 9 h after irradiation. In U373-MG cells the absolute expression index of transferrin receptors increased during the 24 h after irradiation, and the greatest increase was 45% above control at 9 h. The absolute expression index of IGF1R increased during the 12 h after irradiation with a maximum increase of 33% above control at 6 h. The absolute expression index of IL4R decreased with time after irradiation. In T98-G cells, the absolute expression index of both transferrin receptors and IL4R decreased after irradiation. The results suggest that the expression of growth factor receptors on brain tumor cells may be influenced by radiation. The effect of ionizing radiation on receptor expression should be considered when administration of targeted toxin is combined with radiation. Similar studies with other growth factor receptors used in targeted toxin therapy are recommended.

The prognosis of malignant brain tumors is poor in spite of aggressive treatment. Immunotoxin therapy is a novel approach for the treatment of tumors. Targeted fusion toxins, chimeric protein consisting of the cytotoxic domain of the natural toxin and carrier ligands such as a growth factor or an antibody, have been introduced in the treatment of malignant central nervous system (CNS) tumors, with promising results. The toxin is internalized into the cytosol of the target cell via cell-surface receptors and it is essential for these receptors on the tumor cell to be highly expressed in order for the immunotoxin to have specific anti-tumor activity. Studies on expression of cell-surface receptor for immunotoxin targeting was performed on transferring (TR), insulin-like growth factor-1 (IGF-1R), and interleukin-4 (IL-4R) receptors of human glioblastoma (U373-MG and T98-G) and medulloblastoma (Daoy) cell lines, and the effect of irradiation on expressibility of these receptors was studied. Recombinant diphtheria toxin–murine interleukin-4 conjugate (DT 390 –mIL4) was developed and its cytotoxic efficacy against murine glioblastoma (SMA-560) and neuroblastoma (Neuro-2a and NB41-A3) cell lines was examined, and the combined effect with irradiation was tested. Receptors were expressed in all cases except IGF-1R on T98-G. After irradiation, TR expression was increased for Daoy, IGF-1R expression was increased on Daoy and U373-MG, and IL-4R expression was decreased on Daoy and U373-MG. DT 390 –mIL4 exhibited dose-dependent, specific cytotoxic effects on all cell lines tested with IC 50 (concentration of DT 390 –mIL4 that inhibit 50% of protein synthesis) value of 0.56×10 −9 M in SMA-560, 1.28×10 −9 M in Neuro-2a and 0.95×10 −10 M in NB41-A3. Cytotoxicity was additive when DT 390 –mIL4 at 10 −9 M was administered with irradiation. Targeted fusion toxins are characterized by great potency and high specificity with minimal damage to normal neuronal tissue, and interleukin-4 receptor is one of the proper targets for fusion toxin. The cytotoxicity of the immunotoxin is additive when it is administrated with irradiation. Targeted toxin therapy is a promising adjuvant treatment modality for the malignant brain tumors.

Objective:To evaluate the safety and efficacy of stereotactic radiosurgery (SRS) compared to fractionated stereotactic radiation therapy (FSRT) for meningiomas treated over a seven year period.Methods and materials:Of the 53 patients (15 male and 38 female) with 63 meningiomas, 35 were treated with SRS and the 18 patients with tumors adjacent to critical structures or with large tumors were treated with FSRT. The median doses for the SRS and the FSRT groups were 1400 cGy (500- 4500 cGy) and 5400 cGy (4000-6000 cGy) respectively. Median target volumes for SRS and FSRT were 6.8 ml and 8.8 ml respectively. The median follow-up for the SRS and FSRT groups were 38 months (4.1-97 months) and 30.5 months (6.0-63 months) respectively.Results:The five-year tumor control probability (TC) for benign versus atypical meningiomas were 92.7% vs. 31% (P=.006). The three-year TC were 92.7% vs. 93.3% for SRS vs. FSRT groups respectively (P=.62). For benign meningiomas, the three-year TC were 92.9% vs. 92.3% for the SRS group (29 patients) vs. FSRT group (14 patients) respectively (P=.77). Two patients in the SRS group and one in the FSRT group developed late complications.Conclusion:Preliminary data suggest that SRS is a safe and effective treatment for patients with benign meningiomas. Fractionated stereotactic radiation therapy with conventional fractionation appeared to be an effective and safe treatment alternative for patients not appropriate for SRS. A longer follow-up is required to determine the long-term efficacy and the toxicity of these treatment modalities.

Object The authors evaluated the role of stereotactic radiosurgery (SRS) in patients with multiple brain metastases by analyzing prognostic factors that predict survival. Methods Between March 1991 and January 1999, 83 patients with multiple brain metastases underwent SRS in which they used a 6 mV linear accelerator. The median radiation dose of 15 Gy (range 6–50 Gy) was delivered to the 40 to 90% (median 87%) isodose line encompassing the target. Actuarial overall survival was calculated from the date of SRS by using the Kaplan–Meier method. Univariate comparisons of survival between different groups were performed using a log-rank test. All 83 patients were included in the calculation of overall survival. Actuarial overall survival was 22% at 1 year and 13% at 2 years, and a median survival of 5.4 months (range, 0.3–28.8 months) was demonstrated. Variables that predicted survival were Karnofsky Performance Scale (KPS) score, extracranial disease status, and the number of intracranial metastases. Median survival in patients with a KPS score greater than as compared with less than 70 was 9.1 and 2.7 months, respectively (p = 0.002). Median survival when comparing absence and presence of extracranial disease was 9.9 and 4.1 months, respectively (p = 0.02). Median survival in patients harboring two, three, or four or more lesions was 6.6 months, 5.4 months, and 2.7 months, respectively (p = 0.02). In patients with a KPS score greater than or equal to 70 and with three or fewer lesions, median survival was 7 months or longer. In patients with four or more lesions median survival was 7.4 months for those with no extracranial disease and 2.4 months for those with extracranial disease. Other variables tested (sex, histological tumor type, previous resection, location of metastases, treatment modality, and tumor status) did not influence outcome. Conclusions The absence of extracranial disease, a KPS score greater than or equal to 70, and fewer number of metastases were shown to be significant predictors of longer survival. Stereotactic radiosurgery appears to be a reasonable therapeutic option in patients with up to three lesions when their KPS score is greater than or equal to 70, regardless of extracranial disease status. In those with four or more metastases, however, SRS should be limited to those with no extracranial disease.

Purpose: To evaluate the efficacy of stereotactic radiotherapy (SRT) in patients with recurrent high-grade gliomas by comparing two different treatment regimens, single dose or fractionated radiotherapy. Methods and Materials: Between April 1991 and January 1998, 71 patients with recurrent high-grade gliomas were treated with SRT. Forty-six patients (65%) were treated with single dose radiosurgery (SRS) and 25 patients (35%) with fractionated stereotactic radiotherapy (FSRT). For the SRS group, the median radiosurgical dose of 17 Gy was delivered to the median of 50% isodose surface (IDS) encompassing the target. For the FSRT group, the median dose of 37.5 Gy in 15 fractions was delivered to the median of 85% IDS. Results: Actuarial median survival time was 11 months for the SRS group and 12 months for the FSRT group ( p = 0.3, log-rank test). Variables predicting longer survival were younger age ( p = 0.006), lower grade ( p = 0.0006), higher Karnofsky Performance Scale (KPS) ( p = 0.0005), and smaller tumor volume ( p = 0.02). Patients in the SRS group had more favorable prognostic factors, with median age of 48 years, KPS of 70, and tumor volume of 10 ml versus median age of 53 years, KPS of 60, and tumor volume of 25 ml in the FSRT group. Late complications developed in 14 patients in the SRS group and 2 patients in the FSRT group ( p Conclusion: Given that FSRT patients had comparable survival to SRS patients, despite having poorer pretreatment prognostic factors and a lower risk of late complications, FSRT may be a better option for patients with larger tumors or tumors in eloquent structures. Since this is a nonrandomized study, further investigation is needed to confirm this and to determine an optimal dose/fractionation scheme.

Age-related macular degeneration (AMD) is the leading cause of visual loss among adults 65 years and older in western countries. Of patients with AMD who experience severe loss of vision, approximately 90% do so because of choroidal neovascularization (CNV). Visual loss is most severe when the CNV occurs directly under the fovea. Radiation-treated patients show some stabilization of visual acuity and reduction in extent of CNV compared to similar patients managed by observation alone. Various external beam radiation field arrangements were used to deliver the radiation treatments. The stereotactic radiation delivery technique employed in this study allows precise delivery of radiation to the target with much less radiation delivered to nearby sensitive structures (i.e., lens, optic nerves, optic chiasm, and contralateral eye). This aim of this paper is to describe our stereotactic technique for treatment of CNV, and the method we used for target definition and eye immobilization. We also compare the stereotactic technique with other techniques reported in the literature with regard to dose distributions, dose-volume histograms, and normal tissue complication probabilities (NTCP). We found that the position of the eye can be reproduced from one treatment fraction to the next, that the target can be localized accurately, and that stereotactic radiotherapy minimizes the dose to adjacent and surrounding normal structures while providing a homogeneous dose to the target area.

The efficacy of stereotactic radiosurgery (SRS) was evaluated for patients with single brain metastasis from extracranial primary cancer and the outcome was compared with that of external whole brain irradiation (WBI) alone or with surgical resection. Between January 1976 and December 1996, 225 patients with single brain metastases were treated in the Department of Therapeutic Radiology—Radiation Oncology at the University of Minnesota Hospital. One hundred six patients (47%) were treated with WBI alone (Group 1), 71 patients (32%) underwent surgical resection prior to WBI (Group 2), and 48 patients (21%) underwent SRS ± WBI (Group 3). The most common site of primary cancer was the lung (40%), followed by breast (14%), unknown primary (11%), skin (malignant melanoma, 9%), gastrointestinal tract (8%), kidney (renal cell carcinoma, 8%), gynecological organs (3%), and other (6%). Median dose to the whole brain was 3750 cGy in 15 fractions (range, 2000–5000 cGy). Median radiosurgical dose of 1750 cGy (range, 1200–4000 cGy) was delivered to the 40 to 90% isodose line encompassing the target. Actuarial survival was calculated from the date of treatment using the Kaplan–Meier method and statistical significance was assessed with the log-rank test. Actuarial median survival was 3.8 months for Group 1 (range, 1–84 months), 10.5 months for Group 2 (range, 1–125 months), and 9.8 months for Group 3 (range, 1–51 months). Survival at 1 and 2 years was 20% and 8% for Group 1, 47% and 18% for Group 2, and 37% and 27% for Group 3, respectively. Group 2 (surgery + WBI) and Group 3 (SRS ± WBI) had a statistically significant survival advantage over Group 1 (WBI alone) (p < 0.0001, log-rank test). No survival advantage was found between Groups 2 and 3 (p = 0.69, log-rank test). Our retrospective data suggest that SRS (± WBI) improves survival when compared to WBI alone and is comparable to surgical resection and WBI. Given that SRS is minimally invasive, is able to treat lesions in surgically inaccessible locations, and is potentially more cost-effective than surgery, it is a reasonable and potentially more attractive alternative to surgery in the management of single brain metastasis.

In this study we evaluate prognostic factors that predict local-regional control and survival following stereotactic radiosurgery (SRS) in patients with brain metastasis and establish guidelines for patient selection. Our evaluation is based on 73 patients with brain metastasis treated with SRS at the University of Minnesota between March 1991 and November 1995. The ability of stereotactic radiosurgery to improve local control in patients with brain metastases is confirmed in our study in which only 6 of 62 patients failed locally after SRS, with an actuarial local progression-free survival of 80% at 2 years. Variables that predicted worse prognosis were larger tumor size (p=0.05) for local progression-free survival and multiplicity of metastasis (p=0.03) and infratentiorial location of metastases (p=0.006) for regional progression-free survival. Absence of extracranial disease, KPS ≥ 70, and single intracranial metastasis were significant predictors of longer survival. Patients who fulfill all three criteria will survive longer after SRS (MS=17.7 months) and will most likely benefit from the increase local control in the brain achieved by SRS. Survival in patients who do not meet any of these criteria is very poor (MS=1.5 months), and these patients are less likely to benefit from this treatment. Careful selection of patients for SRS is warranted.

BACKGROUND With the advent of new therapies for metastatic carcinoma to the brain, patterns of intracranial disease and factors influencing survival become important considerations when examining potential treatment options. METHODS The records of 729 patients with metastases to the brain treated during the period between 1973 to 1993 were reviewed. RESULTS Primary tumor histologic type in order of descending frequency included nonsmall cell lung carcinoma (NSCLC), breast carcinoma, small cell lung carcinoma (SCLC), malignant melanoma, renal cell carcinoma, gastrointestinal carcinoma, uterine/vulvar carcinoma, and unknown primary carcinoma. There were 384 patients (53%) with a single brain metastasis, which was encountered most commonly in patients with prostate carcinoma and least often in patients with SCLC. Multiple metastases were present in 345 patients (47%). The median duration from diagnosis to presentation with a brain metastasis was 12 months, ranging from 3 months for patients with NSCLC to 53 months for patients with breast carcinoma. The median duration from presentation with brain metastases to death was 4 months, ranging from 3 months for patients with SCLC to 13 months for patients with prostate carcinoma. Median survival from presentation with brain metastases to death was 5 months for patients with single lesions and 3 months for patients with multifocal disease (P = 0.0001). Median survival for patients with a single lesion was 11 months with surgery and 3 months without surgery (P = 0.0001). Surgery did not significantly influence survival in patients with multiple metastases. CONCLUSIONS Dissemination of systemic carcinoma to the brain continues to carry a poor prognosis. Knowledge of the metastatic patterns and limited survival associated with specific tumor types may be useful for guiding future therapeutic intervention. Cancer 1996;1781-8.

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.

To identify factors associated with the prevalence of radiation proctitis in patients with prostate cancer treated with external radiation therapy and to determine if a dose-response relationship exists.The study included 101 prostate cancer patients treated at the University of Minnesota Hospital and Clinics between 1970 and 1987. Radiation therapy at a daily dose of 175-200 cGy was given for 5 consecutive days per week for 7 weeks with a 10-24-MV linear accelerator. Mean dose to the prostate was 6,795 cGy (range, 5,579-7,417 cGy). Simulation radiographs obtained with rectal barium were analyzed in 51 patients. Doses were calculated at specific points in the boost field.Radiation proctitis developed in 19 patients. No pretreatment or treatment factors were associated with a higher prevalence of proctitis. Statistically significant correlation (P.042) was found between the development of proctitis and dose to the posterior rectum. At chi 2 analysis, proctitis was statistically significantly (P.005) associated with posterior rectal doses of5,000 cGy.A high posterior rectal dose (5,000 cGy) is associated with increased prevalence of proctitis after radiation therapy.

Object The prognosis for patients with primary malignant brain tumors is poor despite aggressive treatment, and tumor recurrence is common regardless of the chosen therapy. Although multimodal treatment does not provide a cure, it is necessary to determine which treatment modalities have the greatest cytotoxic effect and can potentially prolong survival. Immunotoxin therapy is a novel approach for the treatment of tumors, and it has been successfully used in the central nervous system. Because the interleukin (IL)–4 receptor is commonly expressed on brain tumor cells, the purpose of this study was to evaluate the cytotoxic effect of using a modified diphtheria toxin–murine IL-4 (DT390-mIL4) immunoconjugate for the treatment of murine brain tumor cell lines and to determine whether the addition of radiation therapy could potentiate the effect of this agent. Methods Spontaneous murine glioblastoma (SMA-560) and two neuroblastoma (Neuro-2a and NB41A3) cell lines were treated using DT390-mIL4 at different concentrations, and the anti–mouse IL-4 monoclonal antibody (11B11) was used for blocking its cytotoxicity. Other SMA-560 and Neuro-2a cell lines were treated using 500 cGy of radiation 3 hours before DT390-mIL4 treatment. Cytotoxity was evaluated using a trypan blue viability assay. The immunoconjugate exhibited a dose-dependent cytotoxic effect with 50% inhibitory concentration values of 0.56 × 10−9 M in SMA-560, 1.28 × 10−9 M in Neuro-2a, and 0.95 × 10−10 M in NB41A3 cell lines. The cytotoxicity of DT390-mIL4 was specifically blocked by an excess of 11B11. Cytotoxicity was additive when the DT390-mIL4 at 10−9 M immunoconjugate administration was followed by radiation therapy. Conclusions These results indicate that the IL-4 receptor can be a target for diphtheria toxin fusion proteins and that radiation can potentiate the effects of DT390-mIL4. The development of multimodal approaches to treat malignant brain tumors with agents that have different mechanisms of action may be beneficial.

Trigeminal neuralgia (TN) is a disabling pain condition that has classically been treated using either surgical or medical techniques. Several researchers have shown that stereotactically delivered radiation can be an effective tool in the amelioration of this condition. For these studies, the Gamma Knife was used to deliver the radiation treatment. The target location was designated as the proximal nerve at the root entry zone, and doses greater than 70 Gy to the maximum point in a single fraction were found to be effective in controlling pain in 80% of the patients treated. LINAC‐based stereotactic radiosurgery has been notably absent from the treatment of TN, even though it has many similarities to Gamma Knife‐based stereotactic radiosurgery. The aim of this paper is to describe our LINAC‐based stereotactic technique for treatment of TN. We also compare treatment of TN using our technique to that using the Gamma Knife. We found that a LINAC‐based treatment of TN can be accomplished with accuracy comparable to treatments delivered using the Gamma Knife. The dose distributions are essentially equivalent for the two treatment approaches. The LINAC‐based system is easy to plan and offers the ability to reduce the involvement of sensitive structures from the treatment fields as well as the Gamma Knife system does. A disadvantage of the LINAC‐based system is the time involved for treatment. PACS number: 87.53.Tf 87.56.Da

Purpose: To examine radiation dose response for low-grade glioma (LGG) based on our institutional experience and to review the literature on this topic. Methods and Materials: Sixty-seven patients with supratentorial low-grade nonpilocytic astrocytomas (n=36) or oligodendrogliomas (n=31) were treated with postoperative radiation therapy (RT). Twenty-seven patients (group A) received 5520 cGy; 24 patients (group B) received 5940 cGy; and 16 patients (group C) received 6375 cGy. The corresponding median follow-up was 60, 35 and 91 months, respectively. Results: The disease-specific survival (DSS) at 5 and 10 years were 90.2% and 56.2%, 67.6% and 47.3%, and 62.5% and 50% for groups A, B and C, respectively (P=0.40). Only a greater extent of surgical resection and absence of contrast enhancement predicted DSS on multivariate analyses. Patients receiving higher doses of RT had higher complication rates. Conclusion: Our data confirmed the lack of radiation dose response for supratentorial LGG as demonstrated in the previous randomized trials. The radiation dose should not exceed 5520 cGy because dose escalation did not result in an improvement of DSS and it also increased the complication rates. Future research should focus on the eradication of radioresistant clones either by the improvement of surgical resection or the use of cytotoxic agents that can target on the radioresistant tumor cells.

Three-dimensional conformal radiation therapy (3D-CRT) is a promising new treatment technique based on the principle that improved precision in both tumor definition and dose delivery will enhance outcomes by maximizing dose to the tumor area while minimizing dose to normal tissue. Using a cost-benefit analysis, in terms of outcomes, we first examined the overall risks and benefits of 3D-CRT. We then used the treatment of prostate cancer as a model to compare actual clinical outcomes reported between 3D-CRT and standard radiation therapy (SRT). Our analysis shows that application of 3D-CRT to the clinical setting remains difficult because of the continual difficulties of target definition, and that dose escalation cannot yet be justified on the basis of the lack of benefit found, and suggested increased late toxicity, in most of the dose escalation series compared with SRT.

Although stereotactic radiosurgery has been studied extensively in adults, the data demonstrating its efficacy in children is limited. Medical records were reviewed to identify the indications for and outcomes of patients treated with this modality. Linear accelerator-based radiosurgery was used to treat 11 recurrent brain tumors and one posterior fossa arteriovenous malformation over 3 years. The mean and median age of those treated was 10 and 8 years, respectively (range 1-20 years). Patients received 700 to 3,000 cGy delivered to the 50-90% isodose line in a single fraction. The mean and median follow-up was 15 and 17 months, respectively. Three of the four children with malignant disease died 6 to 9 months after treatment. One patient died of recurrence outside the treatment field. Another child died of complications related to radiation injury, and the third died of disease progression. All children with low-grade tumors remain alive without complications. Six of eight (75%) children exhibit substantial radiographic reductions in tumor size. The child with a vascular malformation has been followed for 26 months, without hemorrhage and with a radiographically proved decrease in size. Our series suggests that radiosurgery has limited usefulness in malignant disease. Therapeutic response is influenced by lesion size and/or location. Stereotactic radiosurgery appears to be effective in children with low-grade intracranial tumors or arteriovenous malformations. Further experience is required to establish the role and long term side effects of radiosurgery in pediatric patients.