The addition of SPECT/CT lymphoscintigraphy to breast cancer radiation planning spares lymph nodes critical for arm drainage.

BACKGROUND: This prospective cohort study was designed to determine whether the amount of radiation delivered to the nonpathological lymph nodes (LNs) that drain the arm can be significantly reduced by integrating single-photon emission computed tomography (SPECT)/computed tomography (CT) scans into radiation treatment planning. METHODS: SPECT-CT scans were acquired for the 28 patients with stage I or II breast cancer and fused with the routinely obtained radiation oncology planning CT scans. Arm-draining LNs were contoured with 0.5-cm margins automatically using a threshold of 50% maximum intensity. Two treatment plans were generated: 1 per routine clinical practice (standard; STD) and the second (modified; MOD) with treatment fields modified to minimize dose to the arm-draining LNs visible on SPECT/CT images without interfering with the dosage delivered to target tissues. Participants were treated per the MOD plans. Arm volumes were measured prior to radiation and thereafter at least three subsequent 6-month intervals. RESULTS: Sixty-eight level I-III arm-draining LNs were identified, 57% of which were inside the STD plan fields but could be blocked in the MOD plan fields. Sixty-five percent of arm-draining LNs in the STD versus 16% in the MOD plans received a mean of ≥10 Gy, and 26% in the STD versus 4% in the MOD plans received a mean of ≥40 Gy. Mean LN radiation exposure was 23.6 Gy (standard deviation 18.2) with the STD and 7.7 Gy (standard deviation 11.3) with the MOD plans (P<.001). No participant developed lymphedema. CONCLUSIONS: The integration of SPECT/CT scans into breast cancer radiation treatment planning reduces unnecessary arm-draining LN radiation exposure and may lessen the risk of lymphedema.

American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) practice guideline for the performance of total body irradiation (TBI).

Total body irradiation (TBI) is a specialized radiotherapy technique. It is frequently used as a component of treatment plans involving hematopoietic stem cell transplant for a variety of disorders, most commonly hematologic malignancies. A variety of treatment delivery techniques, doses, and fractionation schemes can be utilized. A collaborative effort of the American College of Radiology and American Society for Radiation Oncology has produced a practice guideline for delivery of TBI. The guideline defines the qualifications and responsibilities of the involved personnel, including the radiation oncologist, physicist, dosimetrist, and radiation therapist. Review of the typical indications for TBI is presented, and the importance of integrating TBI into the multimodality treatment plan is discussed. Procedures and special considerations related to the simulation, treatment planning, treatment delivery, and quality assurance for patients treated with TBI are reviewed. This practice guideline can be part of ensuring quality and safety in a successful TBI program.

Stereotactic radiosurgery for patients with recurrent intracranial ependymomas.

The objective of the study is to define the tumor control rate and complications associated with stereotactic radiosurgery (SRS) for patients with recurrent intracranial ependymoma. Retrospective review of 26 patients (49 tumors) having SRS between 1990 and 2008. Twenty-five patients (96 %) had undergone one or more craniotomies; one patient underwent SRS for a metastatic tumor after resection of a spinal ependymoma. Nineteen patients (73 %) had received cranial external beam radiotherapy (median dose, 54 Gy). Eight patients (31 %) were less than 18 years old. The median target volume was 2.2 cm(3) (range, 0.3-66.6); the median tumor margin dose was 18 Gy (range, 12-24). The median follow-up after SRS was 3.1 years (range, 3 months-13.1 years). The median overall survival after SRS was 5.5 years. The 1-year and 3-year survival rates were 96 and 69 %, respectively. Local tumor control (LC) was achieved in 33 of 49 lesions (67 %) with a median time to progression of 14.7 months (range, 2.9 months-11.2 years). The 1-year and 3-year progression-free survival rates were 80 and 66 %, respectively. The 1-year and 3-year LC rate was 85 and 72 %, respectively. On univariate analysis, higher tumor grade was associated with worse OS (grade 3-4, 27 % vs grade 2, 82 %, p = 0.04). Seven patients (27 %) had distant tumor progression and two patients (8 %) had symptomatic radiation necrosis after SRS. SRS for recurrent intracranial ependymoma provided good LC and may improve survival for patients with limited recurrent disease after prior treatment.

Stereotactic radiosurgery for recurrent or unresectable pilocytic astrocytoma.

PURPOSE: To report the outcomes in patients with recurrent or unresectable pilocytic astrocytoma (PA) treated with Gamma Knife stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Retrospective review of 18 patients (20 lesions) with biopsy-confirmed PA having SRS at our institution from 1992 through 2005. RESULTS: The median patient age at SRS was 23 years (range, 4-56). Thirteen patients (72%) had undergone one or more previous surgical resections, and 10 (56%) had previously received external-beam radiation therapy (EBRT). The median SRS treatment volume was 9.1 cm(3) (range, 0.7-26.7). The median tumor margin dose was 15 Gy (range, 12-20). The median follow-up was 8.0 years (range, 0.5-15). Overall survival at 1, 5, and 10 years after SRS was 94%, 71%, and 71%, respectively. Tumor progression (local solid progression, n = 4; local solid progression + distant, n = 1; distant, n = 2; cyst development/progression, n = 4) was noted in 11 patients (61%). Progression-free survival at 1, 5, and 10 years was 65%, 41%, and 17%, respectively. Prior EBRT was associated with inferior overall survival (5-year risk, 100% vs. 50%, p = 0.03) and progression-free survival (5-year risk, 71% vs. 20%, p = 0.008). Nine of 11 patients with tumor-related symptoms improved after SRS. Symptomatic edema after SRS occurred in 8 patients (44%), which resolved with short-term corticosteroid therapy in the majority of those without early disease progression. CONCLUSIONS: SRS has low permanent radiation-related morbidity and durable local tumor control, making it a meaningful treatment option for patients with recurrent or unresectable PA in whom surgery and/or EBRT has failed.

Excellent local control and survival after intraoperative and external beam radiotherapy for pediatric solid tumors: long-term follow-up of the Mayo Clinic experience.

Use of external beam radiotherapy (EBRT) for pediatric solid malignancies is generally limited by the tolerance of normal tissue in developing organs. Intraoperative electron radiotherapy (IOERT) allows a more focal delivery of radiation dose because vital organs can be displaced and avoided during treatment. From February 1983 to July 2003, 20 children underwent IOERT for treatment of locally advanced or recurrent malignancies of the extremity or abdominopelvic area. All patients underwent EBRT and received IOERT doses of 7.5 to 25 Gy with 6-MeV to 15-MeV electrons. At a median follow-up of 11.6 years (range, 2.1 to 25.5 y), 13 patients (65%) were alive and without evidence of disease. Patients who underwent gross total resection had better local control (88% vs. 67%) and survival (71% vs. 33%) than patients for whom the resection was not achieved. Among 7 patients, 11 grade 3 toxicity events were reported. No grade >3 toxicities or second malignancies were observed during follow-up. Use of IOERT in combination with surgery and EBRT in management of pediatric solid malignancies provides excellent local control with reasonable toxicity. IOERT should be considered as an integral part of a multimodality regimen for pediatric solid malignancies, especially for patients with abdominopelvic malignancies.

Long-term follow-up of dose-adapted and reduced-field radiotherapy with or without chemotherapy for central nervous system germinoma.

PURPOSE: To update our institutional experience with neoadjuvant chemotherapy and minimized radiotherapy vs. radiation monotherapy for intracranial germinoma. METHODS AND MATERIALS: We retrospectively reviewed records of 59 patients with diagnosis of primary intracranial germinoma between 1977 and 2007. Treatment was irradiation alone or neoadjuvant platinum-based chemotherapy and local irradiation (initial tumor plus margin) for patients with localized complete response and reduced-dose craniospinal irradiation for others. RESULTS: For the chemoradiotherapy group (n = 28), median follow-up was 7 years. No patient died. The freedom from progression (FFP) rate was 88% at 5 years and 80% at 10 years. In 4 patients, disease recurred 1.1 to 6.8 years after diagnosis. All were young male patients who received 30.6 Gy to local fields after complete response to chemotherapy. The FFP rate was 88% for local irradiation vs. 100% for more extensive fields (p = .06). For the radiotherapy-alone group (n = 31), median follow-up was 15 years. Overall and disease-free survival rates were 93% and 93% at 5 years and 90% and 87% at 15 years. In 5 patients, disease recurred 1.1 to 4.9 years after diagnosis. Most patients in this group were young men 18 to 23 years of age with suprasellar primary disease treated with about 50 Gy to local fields. The FFP rate was 44% for local irradiation vs. 100% for more extensive fields (p < .01). CONCLUSIONS: The addition of neoadjuvant chemotherapy to local-field radiotherapy reduced central nervous system cancer recurrence when high-risk patients were excluded by thorough pretreatment staging. There was trend toward improved central nervous system tumor control when larger fields (whole brain, whole ventricle, or craniospinal axis) were used.

Phase II NCCTG trial of RT + irinotecan and adjuvant BCNU plus irinotecan for newly diagnosed GBM.

Irinotecan has radiosensitizing effects and shows synergism with nitrosoureas. We performed a Phase II study of RT and irinotecan, followed by BCNU plus irinotecan in newly-diagnosed GBM. The MTD for patients receiving enzyme-inducing anticonvulsants (EIAC) was as follows: irinotecan 400 mg/m(2)/week on Days 1, 8, 22 and 29 during RT, followed by BCNU 100 mg/m(2) Day 1, and irinotecan, 400 mg/m(2) on Days 1, 8, 22 and 29, every 6 weeks. The MTD for non-EIAC patients was as follows: irinotecan 125 mg/m(2)/week on Days 1, 8, 22 and 29 during RT, followed by BCNU 100 mg/m(2) Day 1 and irinotecan 75 mg/m(2) Days 1, 8, 22 and 29, every 6 weeks. Median OS was 10.8 mos. (95% CI: 7.7-14.9); OS at 12 months was 44.6% (95% CI: 33.3-59.8) and PFS 6 was 28.6% (95% CI: 18.9-43.2). Patients went off treatment due to adverse events (7%), refusal (11%), progressive disease (48%), death (9%), and other (9%); 16% completed protocol treatment. Survival was similar in patients with variant (6/7 or 7/7) and wild-type (6/6) UGT1A1*28 genotypic alleles. Grade 3-4 toxicity was more common in non-EIAC patients with variant alleles. SN-38 C(max) and AUC in EIAC patients receiving 400 mg/m(2) irinotecan were 20.9 ng/ml and 212 ng/ml h, and in non-EIAC patients receiving 125 mg/m(2), 15.5 ng/ml and 207 ng/ml h. SN-38 AUC varied by UGT1A1*28 status in non-EIAC patients. This regimen was not significantly active and radiosensitization was not observed. Non-EIAC patients with UGT1A1*28 variant alleles appear particularly sensitive to toxicity from irinotecan.

Trends in surgical treatment of breast cancer at Mayo Clinic 1980-2004.

The study encompassed the time period January 1980 through December 2004. During this time 9485 women underwent mastectomy, 6847 women underwent breast conserving surgery (BCS) and 2477 women underwent breast radiotherapy (RT) for breast cancer. Linear regression modeling was used to quantify the rate of change in the proportion of women undergoing mastectomy during specific time periods. Chi-square tests were used to compare the proportion of women with a breast cancer less than 3 cm in size undergoing mastectomy the year prior to and the year after a specific event. There was a significant decrease in the number and proportion of mastectomies performed, an increase in the number of BCS procedures performed and an increase in the number of women undergoing breast RT around the times of (1) the employment of a young surgeon trained in BCS, (2) publication of the NIH Consensus Statement and (3) establishment of a multidisciplinary Breast Clinic.

Effects of scatter radiation on ICD and CRT function.

BACKGROUND: Effects of direct radiation on implantable cardiac devices have been well studied. However, the effects of scatter radiation are not as clear. Recommendations on management of patients with implantable cardiac devices undergoing radiotherapy are based on limited studies mostly involving pacemakers. We sought to elucidate the effects of scatter radiation on implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT)-ICDs. METHODS: We exposed 12 ICDs and eight CRT-ICDs to 400 cGy of scatter radiation from a 6-MV photon beam. Devices were programmed with nominal parameters and interrogated prior to radiation, after each fraction, upon completion of the radiation course and again 1 week later. A retrospective review of patients undergoing radiotherapy at the Mayo Clinic-Rochester between 2002 and 2007 in whom the device was outside the radiation field was also performed. There were 13 patients with devices undergoing radiotherapy during this time period, 12 of whom were interrogated prior to and after radiation. RESULTS: Interrogation reports were reviewed for device reset or parameter changes. There was no evidence of reset or malfunction during or after radiation. Also, no episodes of device reset, inappropriate sensing or therapy, or changes in programmed parameters were found in our review of patients undergoing radiotherapy. CONCLUSIONS: Device reset or malfunction associated with scatter radiation likely represents an unpredictable, rare occurrence. While we see no clear contraindication to radiotherapy in patients with ICDs or CRT-ICDs, precautions should be taken to avoid direct radiation exposure and to closely evaluate patient outcomes before and after the radiation course.

Imaging guidelines for children with Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group Bone Tumor Committee.

The Children's Oncology Group (COG) is a multi-institutional cooperative group dedicated to childhood cancer research that has helped to increase the survival of children with cancer through clinical trials. These clinical trials include a standardized regimen of imaging examinations performed prior to, during, and following therapy. This article presents imaging guidelines developed by a multidisciplinary group from the COG Bone Tumor Committee. These guidelines provide both required and recommended studies. Recommended examinations may become required in the future. These guidelines should be considered a work in progress that will evolve with advances in imaging and childhood cancer research.

Gamma knife radiosurgery for patients with nonfunctioning pituitary adenomas: results from a 15-year experience.

PURPOSE: To evaluate the efficacy and complications of stereotactic radiosurgery for patients with nonfunctioning pituitary adenomas (NFA). METHODS AND MATERIALS: This was a retrospective review of 62 patients with NFA undergoing radiosurgery between 1992 and 2004, of whom 59 (95%) underwent prior tumor resection. The median treatment volume was 4.0 cm(3) (range, 0.8-12.9). The median treatment dose to the tumor margin was 16 Gy (range, 11-20). The median maximum point dose to the optic apparatus was 9.5 Gy (range, 5.0-12.6). The median follow-up period after radiosurgery was 64 months (range, 23-161). RESULTS: Tumor size decreased for 37 patients (60%) and remained unchanged for 23 patients (37%). Two patients (3%) had tumor growth outside the prescribed treatment volume and required additional treatment (fractionated radiation therapy, n = 1; repeat radiosurgery, n = 1). Tumor growth control was 95% at 3 and 7 years after radiosurgery. Eleven (27%) of 41 patients with normal (n = 30) or partial (n = 11) anterior pituitary function before radiosurgery developed new deficits at a median of 24 months after radiosurgery. The risk of developing new anterior pituitary deficits at 5 years was 32%. The 5-year risk of developing new anterior pituitary deficits was 18% for patients with a tumor volume of < or = 4.0 cm(3) compared with 58% for patients with a tumor volume >4.0 cm(3) (risk ratio = 4.5; 95% confidence interval = 1.3-14.9, p = 0.02). No patient had a decline in visual function. CONCLUSIONS: Stereotactic radiosurgery is effective in the management of patients with residual or recurrent NFA, although longer follow-up is needed to evaluate long-term outcomes. The primary complication is hypopituitarism, and the risk of developing new anterior pituitary deficits correlates with the size of the irradiated tumor.

A multidisciplinary approach to the management of breast cancer, part 2: therapeutic considerations.

New approaches to breast cancer treatment have enhanced clinical outcomes and patient care. These approaches include advances in breast irradiation and hormonal and systemic adjuvant therapies. In addition to the identification of new drug targets and targeted therapeutics (eg, trastuzumab), there is renewed re-emphasis in the development of biomarkers for the prediction of response to therapy. One example is the pharmacogenetics of tamoxifen metabolism and the individualization of hormonal therapy. The current treatment of breast cancer continues to evolve rapidly, with new scientific and clinical achievements constantly changing the standard of care and leading to substantial reductions in breast cancer mortality. The goal of this article is to provide clinicians who care for women with breast cancer a multidisciplinary, state-of-the art approach to the treatment of these patients.

A multidisciplinary approach to the management of breast cancer, part 1: prevention and diagnosis.

Breast cancer is the most common cancer among women in the United States, with an estimated 200,000 new cases diagnosed annually. A multidisciplinary focus that entails prevention, diagnosis, and treatment has led to significant strides in the reduction of breast cancer incidence and mortality. Additionally, breast cancer management has become increasingly complex, requiring comprehensive assessment and review of multiple issues that include the role of genetic testing, imaging and breast magnetic resonance imaging, surgical and reconstructive options, and a variety of new adjuvant therapies. It has become more evident that a multidisciplinary team approach that involves a spectrum of breast experts is necessary to provide optimal care to patients. This team includes medical oncologists, breast radiologists, breast pathologists, surgical breast specialists, radiation oncologists, geneticists, and primary care physicians. Furthermore, patient knowledge has increased use of the Internet, and more patients are seeking a multidisciplinary approach to treatment. This review considers information for health care professionals who will facilitate optimal patient care for women at increased risk for or presenting with a new diagnosis of breast cancer. The multidisciplinary team of authors, representing the different disciplines, has selected important state-of-the-art issues that arise in their daily practices for consideration, rather than summarizing what is already available in textbooks.

Prognosis in patients with anaplastic oligoastrocytoma is associated with histologic grade.

BACKGROUND: Anaplastic oligoastrocytomas (AOA) are relatively uncommon high-grade gliomas. While oligodendroglial elements are thought to be associated with better outcomes, the magnitude of the difference is not clear. METHODS: Between 1980 and 1999, Mayo Clinic and the NCCTG conducted 10 trials of radiation therapy and chemotherapy in adults with newly-diagnosed high-grade gliomas. All pathology slides were reviewed by one of the authors (BWS or CG). We grouped patients by cell type and grade, compared survival distributions by the log-rank statistic, and performed multiple variable analyses. RESULTS: Of 1368 patients, 68 (5%) had AOA, including 21 Grade 3 (OA3) and 47 grade 4 (OA4), 153 (11%) had anaplastic astrocytoma (AA), and 1147 (84%) had glioblastoma multiforme (GBM). Patients with OA3 survived significantly longer than those with OA4 (P=0.0001) or AA (P=0.0044). Patients with OA4 lived significantly longer than those with GBM (P=0.0005). The same differences were noted for PFS. Prognostic factors for survival identified by multiple variable analysis were histology, age, ECOG performance score, and extent of surgical resection, but not treatment administered. CONCLUSIONS: Patients with anaplastic oligoastrocytoma have distinct outcomes based upon grade (OA3 vs. OA4) and in comparison with pure astrocytoma (AA or GBM). Future trials which include more than one histologic entity need to report results by cell type and grade and account for the varying prognoses in interpreting treatment outcomes.

Phase III trial of carmustine and cisplatin compared with carmustine alone and standard radiation therapy or accelerated radiation therapy in patients with glioblastoma multiforme: North Central Cancer Treatment Group 93-72-52 and Southwest Oncology Group 9503 Trials.

PURPOSE: In patients with newly diagnosed glioblastoma multiforme, to determine whether cisplatin plus carmustine (BCNU) administered before and concurrently with radiation therapy (RT) improves survival compared with BCNU and RT and whether survival using accelerated RT (ART) is equivalent to survival using standard RT (SRT). PATIENTS AND METHODS: After surgery, patients were stratified by age, performance score, extent of surgical resection, and histology (glioblastoma v gliosarcoma) and then randomly assigned to arm A (BCNU plus SRT), arm B (BCNU plus ART), arm C (cisplatin plus BCNU plus SRT), or arm D (cisplatin plus BCNU plus ART). RESULTS: Four hundred fifty-one patients were randomly assigned, and 401 were eligible. Frequent toxicities included myelosuppression, vomiting, sensory neuropathy, and ototoxicity and were worse with cisplatin. There was no difference in toxicity between SRT and ART. Median survival times and 2-year survival rates for patients who received BCNU plus RT (arms A and B) compared with cisplatin, BCNU, and RT (arms C and D) were 10.1 v 11.5 months, respectively, and 11.5% v 13.7%, respectively (P = .19). Median survival times and 2-year survival rates for patients who received SRT (arms A and C) compared with ART (arms B and D) were 11.2 v 10.5 months, respectively, and 13.8% v 11.4%, respectively (P = .33). CONCLUSION: Cisplatin administered concurrently with BCNU and RT resulted in more toxicity but provided no significant improvement in survival. SRT and ART produced similar toxicity and survival.

Ototoxicity of cisplatin plus standard radiation therapy vs. accelerated radiation therapy in glioblastoma patients.

PURPOSE: To assess the effect of cisplatin (CDDP) plus concurrent radiation therapy on hearing loss. METHODS: 451 patients with glioblastoma multiforme (GBM) were randomly assigned after surgery to: Arm A: Carmustine (BCNU) + standard radiation therapy (SRT); Arm B: BCNU + accelerated radiation therapy (ART: 160 cGy twice daily for 15 days); Arm C: CDDP + BCNU + SRT; or Arm D: CDDP + BCNU + ART. Patients on arms C and D received audiograms at baseline, and prior to the start of RT, and prior to cycles 3 and 6. Otologic toxicities were recorded at each visit. RESULTS: 56% of patients had hearing loss at baseline. 13% and 50% of patients experienced worsening ototoxicity after 1 year of treatment in arms A and B vs. C and D, respectively, with 13% of those on arms C and D experiencing significant ototoxicity (>or= grade 3) at 6 months. Increasing age was associated with an increased risk of ototoxicity. CONCLUSIONS: Increased exposure to CDDP increases the risk of ototoxicity over time. Older patients are more susceptible to hearing loss with CDDP. The low proportion of patients with clinically significant ototoxicity suggests that baseline screening is unnecessary in GBM patients.

Radiation complications and tumor control after 125I plaque brachytherapy for ocular melanoma.

PURPOSE: To determine the outcome of 125I plaque brachytherapy at our institution and identify the risk factors associated with the development of radiation complications, tumor recurrence, and metastasis. PATIENTS AND METHODS: From 1986 to 2000, 156 patients underwent 125I episcleral plaque (COMS design) application for the treatment of ocular melanoma. Chart analysis of follow-up ophthalmologic appointments assessed the incidence of ocular side effects after therapy. Statistical analysis assessed outcomes and significant influencing factors. RESULTS: With a median follow-up of 6.2 years, the 5-year overall survival was 83%. The 5-year disease-specific survival was 91%. Initial local control at 5 years was 92%, with 100% ultimate local control after secondary therapy that included 9 enucleations. The risk of metastasis was 10% at 5 years and 27% at 10 years. Vision stayed the same or improved in 25% of patients, and 44% of patients maintained visual acuity better than 20/200. Thirteen percent of patients experienced chronic pain or discomfort in the treated eye. Dose rates to the tumor apex greater than 90 to 100 cGy/h were associated with increased systemic control but worse radiation toxicity. CONCLUSION: Patients in our series experienced excellent local tumor control. Higher dose rates to the tumor apex were associated with reduced rates of distant metastases but worse ocular function.

Gamma knife radiosurgery of radiation-induced intracranial tumors: local control, outcomes, and complications.

PURPOSE: To determine local control (LC) and complication rates for patients who underwent radiosurgery for radiation-induced intracranial tumors. METHODS AND MATERIALS: Review of a prospectively maintained database (2,714 patients) identified 16 patients (20 tumors) with radiation-induced tumors treated with radiosurgery between 1990 and 2004. Tumor types included typical meningioma (n=17), atypical meningioma (n=2), and schwannoma (n=1). Median patient age at radiosurgery was 47.5 years (range, 27-70 years). The median tumor margin dose was 16 Gy (range, 12-20 Gy). Median follow-up was 40.2 months (range, 10.8-146.2 months). Time-to-event outcomes were calculated with Kaplan-Meier estimates. RESULTS: Three-year and 5-year LC rates were 100%. Three-year and 5-year overall survival rates were 92% and 80%, respectively. Cause-specific survival rates at 3 and 5 years were 100%. Three patients died: 1 had in-field progression 65.1 months after radiosurgery and later died of the tumor, 1 died of progression of a preexisting brain malignancy, and 1 died of an unrelated cause. One patient had increased seizure activity that correlated with development of edema seen on neuroimaging. CONCLUSIONS: LC, survival, and complication rates in our series are comparable to those in previous reports of radiosurgery for intracranial meningiomas. Also, LC rates with radiosurgery are at least comparable to those of surgical series for radiation-induced meningiomas. Radiosurgery is a safe and effective treatment option for radiation-induced intracranial tumors, most of which are typical meningiomas.

Phase II trial of carmustine, cisplatin, and oral etoposide chemotherapy before radiotherapy for grade 3 astrocytoma (anaplastic astrocytoma): results of North Central Cancer Treatment Group trial 98-72-51.

PURPOSE: To evaluate the efficacy of preradiotherapy (RT) chemotherapy with carmustine, cisplatin, and oral etoposide combined with RT in the treatment of newly diagnosed anaplastic astrocytoma. METHODS AND MATERIALS: Therapy consisted of carmustine (40 mg/m(2)/d) on Days 1-3, oral etoposide (50 mg/d) on Days 1-21 and 29-49, and cisplatin (20 mg/m(2)/d i.v.) on Days 1-3 and 29-31. The regimen was repeated every 8 weeks for three cycles, with conventionally fractionated RT (5000 cGy with a 1000-cGy boost) delivered concurrently with the third cycle. RESULTS: A total of 29 patients were enrolled between December 1999 and March 2001. For varying reasons (e.g., progression, refusal, death, or toxicity), only 48% completed the chemotherapy regimen and 76% completed RT. Grade 3-4 toxicities were observed in 14 patients (48%). The primary study endpoint was the 23-month (700-day) survival, the median survival of patients with anaplastic astrocytoma in a previous North Central Cancer Treatment Group trial. To be considered an active treatment, a maximum of 9 patient deaths (of the first 25) were allowed before 700 days. However, 14 patients had died by 700 days after therapy. CONCLUSION: Our results have demonstrated that pre-RT chemotherapy with this regimen is insufficiently active in patients with anaplastic astrocytoma.