Long-term outcomes of spinal ependymomas: an institutional experience of more than 60 cases.

PURPOSE: Spinal ependymomas represent the most common primary intramedullary tumors for which optimal management remains undefined. When possible, gross total resection (GTR) is often the mainstay of treatment, with consideration of radiotherapy (RT) in cases of residual or recurrent tumor. The impact of extent of resection and radiotherapy remain understudied. OBJECTIVE: Report on a large institutional cohort with lengthy follow-up to provide information on long-term outcomes and to contribute to limited data assessing the value of extent of resection and RT. METHODS: Patients with pathologically proven primary spinal ependymoma between 1990 and 2018 were identified. Kaplan-Meier estimates were used to calculate progression-free survival (PFS); local-control (LC) and overall survival (OS). Logistic regression was used to analyze variables' association with receipt of RT. RESULTS: We identified 69 patients with ependymoma of which 4 had leptomeningeal dissemination at diagnosis and were excluded. Of the remaining cohort (n = 65), 42 patients (65%) had Grade II spinal ependymoma, 20 (31%) had Grade I myxopapillary ependymoma and 3 (5%) had Grade III anaplastic ependymoma; 54% underwent GTR and 39% underwent RT. With a median follow-up of 5.7 years, GTR was associated with improved PFS. For grade II lesions, STR+RT yielded better outcomes than STR alone (10y PFS 77.1% vs 68.2%, LC 85.7% vs 50%). Degree of resection was the only significant predictor of adjuvant radiotherapy (p < 0.0001). CONCLUSION: Our findings confirm the importance of GTR in spinal ependymomas. Adjuvant RT should be utilized in the setting of a subtotal resection with expectation of improved disease-related outcomes.

A phase II trial of arsenic trioxide and temozolomide in combination with radiation therapy for patients with malignant gliomas.

Standard treatment for GBM is radiation (RT) and temozolomide (TMZ). Arsenic trioxide (ATO) is synergistic with RT based on several mechanisms of action previously identified, however not tested herein. The MTD of ATO, RT and TMZ was determined in a Phase I trial. We now present the combined Phase I/II data. Patients with newly diagnosed malignant gliomas were eligible for treatment. Patients were treated with RT (60 GY), TMZ (75 mg/m2 daily × 42 days) and ATO 0.20 mg/kg daily in week 1 then twice a week ×5 weeks, after completing RT they were treated with TMZ 5/28 for up to 12 months. MRIs were performed every 8 weeks. A total of 42 patients were enrolled in both the Phase I and II trials for this study treatment. Of the 42 enrolled patients (24 M and 18 W) the median age was 54 (24-80) and median KPS 90 (60-100). 28 patients had a GBM and 14 had anaplastic glioma (AG). All patients completed RT/TMZ/ATO and went on to maintenance TMZ. Median number of post RT cycles of TMZ was 4 (0-12). Median PFS was 7 m for GBM and 75 m for AG and median OS was 17 m for GBM and NR for AG. Best response was CR in 2, SD in 28, PR in 5 and PD in 7. There were no unexpected adverse events. Grade 3 toxicities likely attributable to ATO included prolonged Qtc (n = 1), elevated liver enzymes (n = 2 for ALT/n = 1 for AST) and elevated bilirubin (n = 1). Adding ATO to RT and TMZ is feasible with no increased side effects. The addition of arsenic did not improve overall survival in the GBM patients as compared to historic data. MGMT status was analyzed in 20 of the 42 patients where tissue was available for retrieval and MGMT testing.

Low-Dose Gamma Knife Radiosurgery for Vestibular Schwannomas: Tumor Control and Cranial Nerve Function Preservation After 11 Gy.

OBJECTIVES: This study aims to report tumor control rates and cranial nerve function after low dose (11.0 Gy) Gamma knife radiosurgery (GKRS) in patients with vestibular schwannomas. METHODS: A retrospective chart review was performed on 30 consecutive patients with vestibular schwannomas treated from March 2004 to August 2010 with GKRS at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. The marginal dose for all patients was 11.0 Gy prescribed to the 50% isodose line. Median follow-up time was 42 months. The median treatment volume was 0.53 cm3. Hearing data were obtained from audiometry reports before and after radiosurgery. RESULTS: The actuarial progression free survival (PFS) based on freedom from surgery was 100% at 5 years. PFS based on freedom from persistent growth was 91% at 5 years. One patient experienced tumor progression requiring resection at 87 months. Serviceable hearing, defined as Gardner-Robertson score of I-II, was preserved in 50% of patients. On univariate and multivariate analyses, only higher mean and maximum dose to the cochlea significantly decreased the proportion of patients with serviceable hearing. CONCLUSION: Vestibular schwannomas can be treated with low doses (11.0 Gy) of GKRS with good tumor control and cranial nerve preservation.

Brain metastases management paradigm shift: A case report and review of the literature.

Brain metastases are the most common intracranial tumors in adults, accounting for over half of all lesions. Whole-brain radiation therapy (WBRT) has been a cornerstone in the management of brain metastases for decades. Recently, stereotactic radiosurgery (SRS) has been considered as a definitive or postoperative approach instead of WBRT, to minimize the risk of cognitive impairment that may be associated with WBRT. This is the case report of a 74-year-old female patient who was diagnosed with lung cancer in November, 2002, and histopathologically confirmed brain metastases in January, 2005. The patient received 5 treatments with Gamma Knife SRS for recurring brain metastases between 2005 and 2014. The patient remains highly functional, with stable intracranial disease at 10 years since first developing brain metastases, and with stable lung disease. Therefore, Gamma Knife SRS is a safe and effective treatment modality for patients with recurrent intracranial metastases, with durable local control and minimal cognitive impairment.

Survival after surgery and stereotactic radiosurgery for patients with multiple intracranial metastases: results of a single-center retrospective study.

OBJECTIVES: Patients with systemic cancer and a single brain metastasis who undergo treatment with resection plus radiotherapy live longer and have a better quality of life than those treated with radiotherapy alone. Historically, whole-brain radiotherapy (WBRT) has been the mainstay of radiation therapy; however, it is associated with significant delayed neurocognitive sequelae. In this study, the authors looked at survival in patients with single and multiple intracranial metastases who had undergone surgery and adjuvant stereotactic radiosurgery (SRS) to the tumor bed and synchronous lesions. METHODS: The authors retrospectively reviewed the records from an 8-year period at a single institution for consecutive patients with brain metastases treated via complete resection of dominant lesions and adjuvant radiosurgery. The cohort was analyzed for time to local progression, synchronous lesion progression, new intracranial lesion development, systemic progression, and overall survival. The Kaplan-Meier method (stratified by age, sex, tumor histology, and number of intracranial lesions prior to surgery) was used to calculate both progression-free and overall survival. A Cox proportional-hazards regression model was also fitted with the number of intracranial lesions as the predictor and survival as the outcome controlling for disease severity, age, sex, and primary histology. RESULTS: The median overall follow-up among the 150-person cohort eligible for analysis was 17 months. Patients had an average age of 46.2 years (range 16-82 years), and 62.7% were female. The mean (± standard deviation) number of intracranial lesions per patient was 2.5 ± 2.3. The mean time between surgery and stereotactic radiosurgery (SRS) was 3.2 ± 4.1 weeks. Primary cancers included lung cancer (43.3%), breast cancer (21.3%), melanoma (10.0%), renal cell carcinoma (6.7%), and colon cancer (6.7%). The average number of isocenters per treated lesion was 7.6 ± 6.6, and the average treatment dose was 17.8 ± 2.8 Gy. One-year survival for patients in this cohort was 52%, and the 1-year local control rate was 77%. The median (±standard error) overall survival was 13.2 ± 1.9 months. There was no difference in survival between patients with a single lesion and those with multiple lesions (p = 0.319) after controlling for age, sex, and histology of primary tumor. Patients with primary breast histology had the greatest overall median survival (22.9 ± 6.2 months); patients with colorectal cancer had the shortest overall median survival (5.3 ± 1.8 months). The most common cause of death in this series was systemic progression (79%). CONCLUSIONS: These results confirm that 1-year survival for patients with multiple intracranial metastases treated with resection followed by SRS to both the tumor bed and synchronous lesions is similar to established outcomes for patients with a single intracranial metastasis.

Diffusion abnormalities of the corpus callosum in patients receiving bevacizumab for malignant brain tumors: suspected treatment toxicity.

Bevacizumab has been reported to cause diffusion restriction in the tumor bed of patients with malignant gliomas. This study evaluated prolonged diffusion restriction, in the corpus callosum (CC), of patients with malignant brain tumors treated with bevacizumab. We retrospectively reviewed our database of patients treated with bevacizumab for malignant brain tumors looking for those with restricted diffusion in the CC. CC ADC ratio measurements were obtained prior to and following treatment. Correlation was made with biopsy (n = 3) and MR perfusion (n = 7) and PET (n = 4). The temporal evolution of these changes relative to therapy was examined with mixed effects regression analysis. Nine patients (eight malignant gliomas, one malignant meningioma) out of 146 patients were found to have developed areas of diffusion restriction in the CC. These areas tended to enlarge and coalesce over serial MRIs and persisted for up to 22 months. Hypoperfusion was demonstrated in MR perfusion in 7/7. PET was hypometabolic in all 4. Biopsy of the CC showed no tumor in 3/3. ADC ratio measurements indicated a significant overall effect of time (F(16,60) = 11.2; p < 0.0001), consistent with persistent diffusion restriction over the measured time periods. Bevacizumab causes prolonged diffusion restriction in the CC. The negative MR perfusion, FDG PET and histopathology suggest this is a toxicity of bevacizumab and not active tumor. Awareness of these changes can assist in patient care.

Delayed malignant transformation of petroclival meningioma to chondrosarcoma after stereotactic radiosurgery.

Stereotactic radiosurgery (SRS) is often used as adjuvant treatment for residual or recurrent tumor following microsurgical resection of posterior fossa meningiomas. SRS is associated with excellent rates of local control, however long-term complications remain unclear. Secondary malignancy is an often discussed but rarely described complication of SRS. We present a 56-year-old woman who underwent near total resection of a petroclival meningioma, followed by two episodes of SRS over the ensuing 8 years for local recurrence. She returned 14 years after initial diagnosis with neurologic deterioration and was found to have massive recurrence. Pathology was consistent with high-grade chondrosarcoma. The tumor continued to progress despite debulking and proton-beam therapy and the patient died of medical complications. To our knowledge this is the first report of malignant transformation of a meningioma to high-grade chondrosarcoma, further notable due to the remarkable clinical course and delayed presentation after initial surgery and radiosurgery. Though this may have been a de novo tumor, it is also possible that this represents a case of radiation-induced neoplasm. Although SRS continues to gain favor as a treatment modality, delayed malignant degeneration is a potential complication and physicians should counsel patients of this risk.

Intracranial aneurysms in previously irradiated fields: literature review and case report.

OBJECTIVE: Radiotherapy is a common treatment for a variety of disease processes in the central nervous system; it has an ever-increasing number of indications and applications. With the life expectancy of cancer patients increasing, delayed complications of radiation have become more apparent. One such potential complication is the appearance of intracranial aneurysms in the irradiated field. The incidence and natural history of these aneurysms is not well understood. To this end, we performed a review of the literature to analyze the current state of knowledge of these rare aneurysms. Furthermore, we present a case treated at our center. METHODS: We reviewed the literature for all reported cases of intracranial aneurysms appearing in an irradiated field, including any available histopathologic analysis. All papers were included irrespective of the language in which it was published. We calculated the mean age at radiation exposure, the interval between radiation exposure, and aneurysm development and the rate of presentation. Herein we also present a case of an intracranial aneurysm in a 38-year-old patient detected in an irradiation field 33 years after the patient underwent craniospinal irradiation for a medulloblastoma. RESULTS: A total of 46 patients with 69 intracranial aneurysms in irradiation fields were reported between 1978 and 2013. The mean age at radiation exposure was 34 years, and the mean lag time between exposure and diagnosis was 12 years (range, 4 months to 50 years). The median lag time between exposure and diagnosis was shorter in patients older than 40 (6 years). Among the reported aneurysms, 83% were saccular, 9% were fusiform, and 9% were considered pseudo-aneurysms. The Median lag time was 20 years for brachytherapy, 8 years for focused radiation, 9 years for whole brain radiation, and 6 years for SRS. Among reported aneurysms, 55% presented with some form of hemorrhage: intracranial rupture with subarachnoid hemorrhage, epistaxis, or otorrhagia. Only 13% were discovered on routine follow-up or were found incidentally for work-up of unrelated neurologic symptoms. CONCLUSION: Although rarely reported, intracranial aneurysms in irradiation fields may warrant special attention when diagnosed. These aneurysms may have an inherently weaker structure and may be more prone to rupture. Their repair may also be complicated by more fragile and irregular morphology. The increasing longevity of cancer patients suggests that screening for aneurysms at irradiation sites may be warranted, but further studies are needed to validate this approach.

Concordance of patient and caregiver reports in evaluating quality of life in patients with malignant gliomas and an assessment of caregiver burden.

BACKGROUND: Given the neurocognitive impairment experienced by many patients with malignant gliomas, caregiver reports can be critical in assessing the quality of life (QOL) of these patients. In this study, we explored whether assessment of patient QOL by the primary caregiver shows concordance with the patient's self-reported QOL, and we quantified the burden faced by caregivers. METHODS: QOL of 45 patients was evaluated by both the patient and primary caregiver on 3 or more separate occasions using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) instrument, and concordance between the 2 reports was evaluated. Caregiver burden was measured using the Caregiver Quality of Life Index-Cancer (CQOL-C) instrument. RESULTS: Overall, good concordance was observed between the patient and caregiver FACT-Br reports (intraclass correlation coefficient = 0.74). Patient-reported FACT-Br scores were 4.75 (95% CI, 1.44-8.05) points higher than paired caregiver reports on the 200-point scale (P = .008); however, this difference did not achieve clinical significance. Caregiver burden, as measured by the CQOL-C, was significantly greater among caregivers in this study than those previously reported for caregivers of patients with lung, breast, or prostate cancer (P < .001). CONCLUSIONS: Despite minor discrepancies in caregiver assessments of patient QOL relative to patient self-reports, our results suggest that the caregiver assessments can serve as adequate proxies for patient reports. Our results also illustrate the particularly heavy burden faced by caregivers of patients with malignant glioma. Further research into both of these areas is warranted.

Phase I study of arsenic trioxide and temozolomide in combination with radiation therapy in patients with malignant gliomas.

To evaluate the toxicity and maximum tolerated dose (MTD) of arsenic trioxide (ATO) in combination with temozolomide (TMZ) and radiation therapy (RT) in malignant gliomas. A 3 + 3 dose escalation study was performed in patients with newly diagnosed glioblastoma, anaplastic astrocytoma (AA), and anaplastic oligoastrocytoma (AOA). All patients received RT 59-61 Gy in 28-33 fractions, TMZ for 42 days, and ATO 1-2 h prior to RT for 5 days during the first week, then twice weekly until completing RT. Dose levels (DL) were: (1) TMZ 60 mg/m(2)/ATO 0.2 mg/kg; (2) TMZ 75 mg/m(2)/ATO 0.2 mg/kg; (3) TMZ 75 mg/m(2)/ATO 0.25 mg/kg. Dose-limiting toxicity (DLT) was defined as grade 3 non-hematologic toxicity or grade 4 toxicity of any type from enrollment until 3 weeks after finishing RT. 17 patients (13 glioblastoma, 4 AA/AOA) were accrued. Median age was 52 (range 25-80). Median KPS was 90 %. DLT's occurred at DL 2 (grade 4 transaminase elevation) and DL 3 (grade 4 neutropenia and grade 3 QTc prolongation). The MTD of TMZ 75 mg/m(2)/ATO 0.2 mg/kg was safe and well tolerated. A phase II study evaluating the efficacy of this combination is underway.

Brain metastasis in gestational trophoblastic neoplasia: an update.

OBJECTIVE: To update the treatment of brain metastases in gestational trophoblastic neoplasia (GTN) at the Brewer Trophoblastic Disease Center, comparing treatment and outcomes from 1995-2009 with those from 1962-1994. STUDY DESIGN: Thirty-seven patients with GTN who had brain metastases at presentation (25, 68%) or who developed brain metastases during treatment (12, 32%) were treated with chemotherapy and brain irradiation at the Brewer Center between 1962 and 2009 (26 prior to 1995 and 11 since 1995). Patients underwent whole brain irradiation (2400-4000 cGy in 200-300 cGy fractions prior to 1995, and 2400-3000 cGy in 200 cGy fractions since 1995) +/- radiosurgery. RESULTS: Of 11 patients with GTN treated for brain metastases since 1995, 7 (64%) are alive, and 4 died. Six (55%) of the 11 patients treated after 1995 were diagnosed with brain metastases during treatment, 3 (50%) of whom were cured, compared to 6 (23%) of the 26 patients treated before 1995, only 1 (17%) of whom was cured. CONCLUSION: The overall survival for all 37 patients with GTN who had brain metastases from 1962-2009 was 51% (19/37): 46% (12/26) before 1995 and 64% (7/11) after 1995. Survival was significantly influenced by symptoms at presentation: 100% (8/8) for asymptomatic patients versus 41% (7/17) for symptomatic patients (p=0.0005). No patient who died had uncontrolled brain metastases. In our experience, therefore, brain metastases in GTN are curable with a combination of systemic multiagent chemotherapy and whole brain irradiation.

Intracranial relapse rates and patterns, and survival trends following post-resection cavity radiosurgery for patients with single intracranial metastases.

The objective of this study is to evaluate the patterns of relapse and survival trends in patients with single brain metastases treated with post-operative adjuvant Gamma knife stereotactic radiosurgery (GKS) without whole brain radiotherapy (WBRT). Retrospective analysis of all consecutive patients who underwent GKS to the tumor cavity following resection of solitary brain metastasis was performed at a single institution. Between March 2001 and June 2010, 56 patients underwent GKS to the resection cavity following resection of intracranial metastases; no patient received pre- or post-operative WBRT as an adjuvant (salvage WBRT was permissible). The mean marginal dose was 17.1 Gy (range 14-20 Gy). The mean follow-up period was 24 months (range 3-99 months). Five patients (8.9%) had local recurrence in the immediate vicinity of the resection cavity, qualifying as "local failures", and 21 (37.5%) recurred at distant intracranial sites. Median intracranial recurrence free survival was 13 months. Median overall survival was 20.5 months. Salvage interventions were required in 26 patients, and included repeat radiosurgery in 17 patients, further surgery in two patients, and salvage WBRT in eight (14.3%; two of whom had also been locally salvaged with repeat radiosurgery) patients. As expected, avoidance of WBRT results in a high rate of intracranial failure (26/56 patients, 46%), even in well-selected patients with only single brain metastases. As anticipated, the majority of failures (21, 37.5%) are "distant intracranial", and in this well-selected cohort the local failure rate is low (5/56 patients, <9%). All patients failing intracranially (46%) are potential candidates for salvage therapies, but WBRT as salvage was utilized in only 14.3% of patients. The median intracranial relapse-free was 13 months and overall survival was 20.5 months.

Response of an adult patient with pineoblastoma to vorinostat and retinoic acid.

We report the case of an adult patient with pineoblastoma (PBL) who had a complete radiographic response following treatment with vorinostat and retinoic acid. This regimen was used to treat bulky residual tumor that persisted despite radiation therapy (RT) and two cycles of cytotoxic chemotherapy. Vorinostat and retinoic acid were chosen as an alternative to cytotoxic chemotherapy, which our patient was unable to tolerate, based on preclinical data suggesting efficacy of this combination. MRI demonstrated a complete response to this regimen, which continues to remain stable without evidence of recurrence.

Advances in the radiosurgical treatment of large inoperable arteriovenous malformations.

Radiosurgery has proven useful in the treatment of small arteriovenous malformations (AVMs) of the brain. However, the volume of healthy tissue irradiated around large lesions is rather significant, necessitating reduced radiation doses to avoid complications. As a consequence, this can produce poorer obliteration rates. Several strategies have been developed in the past decade to circumvent dose-volume problems with large AVMs, including repeated treatments as well as dose, and volume fractionation schemes. Although success on par with that achieved in lesions smaller than 3 ml remains elusive, improvements over the obliteration rate, the complication rate or both have been reported after conventional single-dose stereotactic radiosurgery (SRS). Radiosurgery with a marginal dose or peripheral dose < 15 Gy rarely obliterates AVMs, yet most lesions diminish in size posttreatment. Higher doses may then be reapplied to any residual nidi after an appropriate follow-up period. Volume fractionation divides AVMs into smaller segments to be treated on separate occasions. Doses > 15 Gy irradiate target volumes of only 5-15 ml, thereby minimizing the radiation delivered to the surrounding brain tissue. Fewer adverse radiological effects with the use of fractionated radiosurgery over standard radiosurgery have been reported. Advances in AVM localization, dose delivery, and dosimetry have revived interest in hypofractionated SRS. Investigators dispensing >or= 7 Gy per fraction minimum doses have achieved occlusion with an acceptable number of complications in 53-70% of patients. The extended latency period between treatment and occlusion, about 5 years for emerging techniques (such as salvage, staged volume, and hypofractionated radiotherapy), exposes the patient to the risk of hemorrhage during that period. Nevertheless, improvements in dose planning and target delineation will continue to improve the prognosis in patients harboring inoperable AVMs.

Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma.

PURPOSE: To determine the event-free survival (EFS) and overall survival of children with average-risk medulloblastoma and treated with reduced-dose craniospinal radiotherapy (CSRT) and one of two postradiotherapy chemotherapies. METHODS: Four hundred twenty-one patients between 3 years and 21 years of age with nondisseminated medulloblastoma (MB) were prospectively randomly assigned to treatment with 23.4 Gy of CSRT, 55.8 Gy of posterior fossa RT, plus one of two adjuvant chemotherapy regimens: lomustine (CCNU), cisplatin, and vincristine; or cyclophosphamide, cisplatin, and vincristine. Results Forty-two of 421 patients enrolled were excluded from analysis. Sixty-six of the remaining 379 patients had incompletely assessable postoperative studies. Five-year EFS and survival for the cohort of 379 patients was 81% +/- 2.1% and 86% +/- 9%, respectively (median follow-up over 5 years). EFS was unaffected by sex, race, age, treatment regimen, brainstem involvement, or excessive anaplasia. EFS was detrimentally affected by neuroradiographic unassessability. Patients with areas of frank dissemination had a 5-year EFS of 36% +/- 15%. Sixty-seven percent of progressions had some component of dissemination. There were seven second malignancies. Infections occurred more frequently on the cyclophosphamide arm and electrolyte abnormalities were more common on the CCNU regimen. CONCLUSION: This study discloses an encouraging EFS rate for children with nondisseminated MB treated with reduced-dose craniospinal radiation and chemotherapy. Additional, careful, step-wise reductions in CSRT in adequately staged patients may be possible.

Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: a pediatric oncology group study.

PURPOSE: Prognosis and outcome of children with isolated CNS relapse of acute lymphoblastic leukemia (ALL) has depended on duration of first complete remission (CR1). This study intensified systemic therapy by delaying CNS radiation for 12 months and tailored CNS radiation by CR1 duration. PATIENTS AND METHODS: Seventy-six children with first isolated CNS relapse of ALL were treated with systemic chemotherapy that effectively penetrates into the CSF and intrathecal chemotherapy for 12 months. Patients with CR1 of less than 18 months received craniospinal radiation (24 Gy cranial/15 Gy spinal), whereas those with CR1 of 18 months or more received cranial radiation only (18 Gy), followed by maintenance chemotherapy. Additionally, asymptomatic patients were enrolled in a thiotepa up-front therapeutic window. RESULTS: Seventy-four (97.4%) of 76 eligible patients achieved a second remission. Overall 4-year event-free survival (EFS) for the 71 precursor B-cell patients was 70.1% +/- 5.8%. CR1 duration and National Cancer Institute (NCI; National Institutes of Health, Bethesda, MD) risk group at initial diagnosis predicted outcome. Patients with CR1 of less than 18 months and 18 months or more had a 4-year EFS of 51.6% +/- 11.3% and 77.7% +/- 6.4% (P = .027), respectively. NCI high- versus standard-risk 4-year EFS was 51.4% +/- 10.8% and 80.2% +/- 6.3% (P = .0018), respectively. A significant difference in EFS between standard risk/CR1 of at least 18 months and both high risk/CR1 of less than 18 months and high risk/CR1 of at least 18 months groups was detected (P = .0068 and .0314, respectively). Response rate to thiotepa was 78%. Most relapses involved the bone marrow, and three second malignancies were reported. CONCLUSION: Twelve months of intensive systemic chemotherapy with reduced dose cranial radiation (18 Gy) is highly effective for children with isolated CNS relapse and CR1 of 18 months or more. Novel strategies are needed for patients with CR1 of less than 18 months.

Phase I study of intraoperative radiotherapy with photon radiosurgery system in children with recurrent brain tumors: preliminary report of first dose level (10 Gy).

PURPOSE: To describe the preliminary results after intraoperative radiotherapy (IORT) with the photon radiosurgery system in children with recurrent brain tumors treated at the first dose level (10 Gy) of a Phase I protocol. METHODS AND MATERIALS: A Phase I IORT dose escalation protocol was initiated at Children's Memorial Hospital to determine the maximal tolerated IORT dose in children with recurrent brain tumors. RESULTS: Fourteen children have received IORT thus far. Eight had been previously irradiated. Thirteen children had ependymoma. The median follow-up was 16 months. Three patients (21%) developed radiation necrosis on follow-up MRI scans 6 to 12 months after IORT. They had not been previously irradiated and had received 10 Gy to a depth of 5 mm. One required surgery and the other two had resolution of their lesions without treatment. All 3 patients were asymptomatic at the last follow-up. No other late toxicity was observed at the last follow-up visit. Eight patients (57%) had tumor control within the surgical bed after IORT. CONCLUSION: Our findings have demonstrated the safety and feasibility of IORT to a dose of 10 Gy to 2 mm in children with previously irradiated brain tumors. IORT to a dose of 10 Gy at 5 mm was associated with a greater complication rate.

Adjuvant gamma knife stereotactic radiosurgery at the time of tumor progression potentially improves survival for patients with glioblastoma multiforme.

OBJECTIVE: Gamma knife stereotactic radiosurgery (GK-SRS) is a safe and noninvasive treatment used as adjuvant therapy for patients with glioblastoma multiforme (GBM). Several studies have yielded conflicting results in the effectiveness of radiosurgery in GBM. This study is a retrospective review of our institutional experience with GK-SRS adjuvant therapy in the treatment of GBM. METHODS: From October 1998 to January 2003, 51 consecutive patients were treated with GK-SRS as an "upfront" adjuvant therapy after surgery or at the time of tumor progression at Northwestern Memorial Hospital. Survival analysis was performed using the Kaplan-Meier actuarial method. Univariate and multivariate analyses of patient characteristics and treatment variables were performed. RESULTS: Treatment with adjuvant GK-SRS yielded a median overall survival of 14.3 months for our cohort. Survival rate of the cohort was 68% at 12 months, 30% at 24 months, and 24% at 36 months. Karnofsky performance score greater than 90 and adjuvant chemotherapy were associated with increased survival on multivariate analysis. Adjuvant GK-SRS performed at tumor progression seems to increase median survival to 16.7 months compared with 10 months when performed after the time of initial tumor resection. Median survival rates by recursive partitioning analysis class breakdown in our cohort are greater than those predicted by other studies. CONCLUSION: GK-SRS is a relatively safe and noninvasive procedure that conferred an improvement in overall survival of GBM patients in our retrospective study. Particularly, GK-SRS may improve overall survival when performed at the time of tumor progression.