Hypofractionation with simultaneous integrated boost after breast-conserving surgery: Long term results of two phase-II trials.

PURPOSE: To analyze long-term results of two multicenter prospective single-arm trials (ARO-2010-01 and ARO-2013-04) investigating adjuvant hypofractionated radiotherapy (HF) with simultaneous integrated boost (SIB) after breast-conserving surgery (BCS). METHODS: Eligible patients had histopathologically confirmed unifocal breast cancer planned for whole breast irradiation plus boost radiotherapy to the tumor bed. In both studies, a total dose of 40 Gy was applied to the whole breast and of 48 Gy to the tumor bed in 16 fractions of 2.5 and 3.0 Gy. Radiotherapy could be given either as three-dimensional conformal radiotherapy (3D-CRT) or as intensity-modulated radiotherapy (IMRT). The primary study objectives were feasibility and security within an observation period of six months. The current investigation focuses on long-term efficacy and toxicities. RESULTS: Between 2011 and 2014, both trials enrolled 300 patients in total. Data from 274 of these patients could be used for the current analysis. The median follow-up time was 60 months and the 5-year disease-free survival 92.1%. Three patients suffered a local recurrence (after 36-72 months) while a regional recurrence occurred in one patient (after 17 months). The 5-year local control rate in the breast was 99.6%. 63.5% of all patients did not report any late radiation-related toxicity, 28.5% reported grade 1 and 7.3% grade 2 toxicities. The highest late toxicity was grade 3 in 2 women (0.7%, telangiectasia and lymphedema of the breast). CONCLUSION: Our analysis demonstrates favorable efficacy and low rates of long-term side effects of HF with SIB after BCS. Randomized controlled phase III trials are ongoing.

Toxicity of two cisplatin-based radiochemotherapy regimens for the treatment of patients with stage III/IV head and neck cancer.

BACKGROUND: This nonrandomized study compared 2 radiochemotherapy regimens for toxicity in 128 patients with stage III/IV head and neck cancer. METHODS: Patients received conventionally fractionated radiotherapy. The total dose to primary tumor and involved lymph nodes did depend on preceding surgery. Patients received 66 to 70 Gy if surgery was not performed, 60 to 66 Gy after R0 resection, 66 Gy after R1 resection, and 70 to 72 Gy after R2 resection. Concurrent chemotherapy consisted of 3 courses cisplatin (100 mg/m(2)/d1,22,43) (group A, N = 61) or 2 courses cisplatin (20 mg/m(2)/d1-5 + 29-33)/5-fluorouracil (5-FU) (600 mg/m(2)/d1-5 + 29-33) (group B, N = 67). RESULTS: Acute toxicity was more severe in group A, especially nausea/vomiting (p = .002), nephrotoxicity (p = .001), ototoxicity (p = .034), and hematotoxicity (p = .049). Forty-eight percent of group A and 10% of group B patients could not complete chemotherapy due to toxicity (p = .018). Late toxicity was similar (p = .99). CONCLUSION: Two courses of fractionated cisplatin (20 mg/m(2)/d) and 5-FU were associated with significantly less acute toxicity than were 3 courses cisplatin (100 mg/m(2)/d).

The inhibition of proliferation and migration of glioma spheroids exposed to temozolomide is less than additive if combined with irradiation.

The aim of this study was to investigate the effect of temozolomide (TZM) in combination with X-rays on proliferation and migration in human glioma spheroids. Multicellular spheroids were derived from GaMg and U87 cell lines. Spheroids were treated with various concentrations of TZM (5 micromol, 0.025 mmol, 0.05 mmol) and irradiation (RT). Proliferation and migration assays were performed. For GaMg spheroids, the proliferation inhibition was 30% (RT), 71%, 79%, 85% (for various TZM concentrations) and 78%, 83%, 90% following RT+TZM. For U87 spheroids, the inhibition of proliferation was 52% (RT), 62%, 78%, 88% (TZM), and 73%, 87%, 92% (RT+TZM). Inhibition of migration for GaMg was 30% (RT), 37%, 63%, 78% (TZM), and 56%, 75%, 84% (RT+TZM). For U87, migration inhibition was 29% (RT), 48%, 52%, 67% (TZM), and 62%, 67%, 73% (RT+TZM). Radiotherapy enhancement ratio (RER) of GaMg/U87 spheroid proliferation was 1.4/1.7 (5 micromol TZM), 1.3/1.8 (0.025 mmol TZM), and 1.4/1.4 (0.05 mmol TZM). RER for migration of GaMg/U87 was 2.2/1.9 (5 micromol TZM), 1.7/1.8 (0.025 mmol TZM), and 1.5/1.4 (0.05 mmol TZM). In terms of inhibition of proliferation and migration, irradiation can lead to an enhancement of the TZM effect in human glioma spheroids, which is less than additive.

Prognostic factors in head-and-neck cancer patients treated with surgery followed by intensity-modulated radiotherapy (IMRT), 3D-conformal radiotherapy, or conventional radiotherapy.

In 148 head-and-neck cancer patients treated with surgery plus radiotherapy (RT), IMRT, 3D-conformal RT, and conventional RT and 10 potential prognostic factors were evaluated for overall survival (OS), metastasis-free survival (MFS), and loco-regional control (LC). On univariate analysis, ECOG performance status, T-stage, AJCC-stage, extent of resection, and pre-RT hemoglobin level (>or=12 g/dl better than <12 g/dl) were significantly associated with treatment outcome, whereas RT technique had no significant impact. On multivariate analysis, performance status maintained significance for OS (P=0.019), AJCC-stage for LC (P=0.034), extent of resection for OS (P=0.045) and MFS (P=0.021), pre-RT hemoglobin for MFS (P<0.001). IMRT was associated with less xerostomia than conformal RT and conventional RT (17% versus 63% and 73%, P=0.037). Otherwise, acute and late toxicity was similar. Outcome was significantly associated with performance status, tumor stage, extent of resection, and pre-RT hemoglobin. The three radiation techniques provided similar disease control. IMRT was effective in significantly reducing xerostomia.

Functional outcome and survival after radiotherapy of metastatic spinal cord compression in patients with cancer of unknown primary.

PURPOSE: Patients with cancer of unknown primary (CUP) account for about 10% of patients with metastatic spinal cord compression (MSCC). This study aims to define the appropriate radiation regimen for these patients. METHODS AND MATERIALS: Data of 143 CUP patients irradiated for MSCC were retrospectively evaluated. Short-course radiotherapy (RT) (1x8 Gy, 5x4 Gy, n = 68) and long-course RT (10x3 Gy, 15x2.5 Gy, 20x2 Gy, n = 75) plus 8 further potential prognostic factors (age, gender, performance status, visceral metastases, other bone metastases, number of involved vertebrae, ambulatory status, time of developing motor deficits before RT) were compared for functional outcome and survival. RESULTS: Improvement of motor function occurred in 10% of patients, no further progression of motor deficits in 57%, and deterioration in 33%. On multivariate analysis, functional outcome was positively associated with slower development of motor deficits (p < 0.001), absence of visceral metastases (p = 0.008) and other bone metastases (p = 0.027), and ambulatory status (p = 0.054), not with the radiation regimen (p = 0.74). Recurrence of MSCC in the irradiated region occurred in 7 patients after median 6 months. Median survival was 4 months. On multivariate analysis, better survival was significantly associated with absence of visceral metastases (p < 0.001), absence of other bone metastases (p = 0.005), ambulatory status (p = 0.001), and slower development of motor deficits (p = 0.030). CONCLUSIONS: For MSCC treatment in patients with CUP, no significant difference was observed between short-course and long-course RT regarding functional outcome and survival. Short-course RT appears preferable, at least for patients with a poor predicted survival, as it is more patient convenient and more cost-effective.

Prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression.

PURPOSE: To evaluate potential prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: The following potential prognostic factors were investigated retrospectively in 1,852 patients irradiated for MSCC: age, sex, performance status, primary tumor, interval between tumor diagnosis and MSCC (< or = 15 v > 15 months), number of involved vertebrae (one to two v > or = three), other bone metastases, visceral metastases, pretreatment ambulatory status, time of developing motor deficits before radiotherapy (faster, 1 to 14 v slower, > 14 days), and radiation schedule (short-course v long-course radiotherapy). RESULTS: On univariate analysis, improved local control of MSCC was associated significantly with favorable histology (breast cancer, prostate cancer, lymphoma/myeloma), no visceral metastases, and long-course radiotherapy. On multivariate analysis, absence of visceral metastases and radiation schedule maintained significance. On univariate analysis, improved survival was associated significantly with female sex, favorable histology, no visceral or other bone metastases, good performance status, being ambulatory before radiotherapy, longer interval between tumor diagnosis and MSCC, and slower development of motor deficits before radiotherapy. Long-course radiotherapy showed a trend. On multivariate analysis, histology, visceral metastases, other bone metastases, ambulatory status before radiotherapy, interval between tumor diagnosis and MSCC, and time of developing motor deficits maintained significance. CONCLUSION: Poorer local control after radiotherapy for MSCC is associated with visceral metastases and short-course radiotherapy. Long-course radiotherapy seems preferable for patients with more favorable prognoses, given that these patients may live long enough to develop MSCC recurrences. Long-term survival after radiotherapy for MSCC may be predicted if several prognostic factors are considered.

Combined modality therapy of gemcitabine and irradiation on human glioma spheroids derived from cell lines and biopsy tissue.

Multicellular tumor spheroids have been used to examine aspects of combined modality treatment since they often recreate the in vivo tumor environment much more closely than other models. The radioenhancement by gemcitabine (dFdC) on human glioma spheroids derived from cell lines (CLS) and biopsy tissue, grown as organotypic multicellular spheroids (OMS), was studied. CLS of GaMg and U87 and OMS of four glioblastoma patients were used. Radiochemosensitvity was determined using migration and proliferation assays on CLS. In OMS, histology and immunohistochemical studies of MIB-1, p53, and p21 expression were examined 24 and 48 h following treatment. Cell death (ethidium homodimer) was studied using a fluorescence cell viability assay. In CLS, combination treatment led to migration inhibition in GaMg and U87 of 85% and 62% (dFdC 46% and 52%, RT 21% and 43%) and proliferation inhibition of 83% and 85%, respectively. Following dFdC + RT in OMS (% of cases), apoptosis and p21 expression increased (50%), p53 expression increased (75%) and cell proliferation decreased (75%). Only minor morphological damage was observed. Confocal laser scanning microscopy identified an increased dead cell core after dFdC + RT (50%). In conclusion, dFdC can lead to an additively radioenhancement in CLS and individual OMS.

Late effects and cosmetic results of conventional versus hypofractionated irradiation in breast-conserving therapy.

BACKGROUND AND PURPOSE: Breast irradiation after lumpectomy is an integral component of breast-conserving therapy (BCT). As the prognosis is general good following BCT, late morbidity and cosmesis are important. The present study compares two different radiation schedules with respect to these two endpoints. PATIENTS AND METHODS: 129 breast cancer patients (pT1-2 pN0-1 cM0) were irradiated between 09/1992 and 08/1994 with either a 22-day fractionation schedule (2.5 Gy to 55 Gy, 4x/week, n = 65) or with a conventional fractionation schedule (28 days, 2.0 Gy to 55 Gy, 5x/week, n = 64), both without additional boost. The equivalent dose of 2-Gy fractions (EQD2) was 55 Gy and 62 Gy, respectively. Late toxicity, assessed according to the LENT-SOMA criteria, and cosmetic outcome, graded on a 5-point scale, were evaluated after a median of 86 months (range 72-94 months) in tumor-free breast cancer patients. RESULTS: LENT-SOMA grade 2/3 toxicity (2.5 Gy vs. 2.0 Gy): breast pain (18% vs. 11%; p = 0.3), fibrosis (57% vs. 16%; p < 0.001), telangiectasia (22% vs. 3%; p = 0.002), atrophy (31% vs. 3%; p < 0.001). Medication to breast pain was taken by 8% versus 9% of patients. Cosmesis was very good/good/acceptable in 75% versus 93% (2.5 Gy vs. 2.0 Gy; p = 0.006). CONCLUSION: Late morbidity was significantly frequent and cosmesis was significantly worse after hypofractionated radiotherapy (2.5 Gy to 55 Gy). However, morbidity was not associated with major implications on daily life.

Health-related quality of life in long term breast cancer survivors treated with breast conserving therapy: impact of age at therapy.

PURPOSE: Aim was to compare the functional status in long-term breast cancer survivors related to age at diagnosis and to asses the effects of adjuvant therapy on health-related quality of life (HRQoL). PATIENTS AND METHODS: Data were obtained from 370 patients after breast conserving therapy (BCT) at follow-up (F/U) visit. The self-administered EORTC QoL questionnaire (C30) and the breast module (QLQ-BR23) measuring global health, global QoL, physical, role, emotional, cognitive and social functioning, body image, sexual function, future perspective and arm/breast symptoms were used. Patients were grouped according to F/U (12 years, 7 years), age at therapy (< 50 years, 50-65 years, >65 years) and adjuvant treatment (none, chemotherapy, hormone replacement therapy). RESULTS: The global HRQoL was increased in patients with longer F/U (p < 0.01). Physical functioning, role functioning and sexual functioning were decreased in patients being older at therapy (> 65 years, p < 0.01). Increased arm symptoms were noticed in older women at longer follow-up. Younger women at therapy complained financial difficulties at follow-up (p < 0.006). Adjuvant chemotherapy and hormone replacement therapy did not affect physical and mental functioning. CONCLUSION: Women of different age treated with BCT for breast cancer should be considered at a different risk for HRQoL disturbance at long term F/U in both, physical and psychological dimensions. In clinical practice, specific identification of those women with negative impact of diagnosis and treatment on long term HRQoL would help for targeted interventions. In clinical studies focusing on HRQoL, the compared groups need to be age-adjusted.

Effects of irradiation and cisplatin on human glioma spheroids: inhibition of cell proliferation and cell migration.

PURPOSE: Investigation of cell migration and proliferation of human glioma cell line spheroids (CLS) and evaluation of morphology, apoptosis, and immunohistochemical expression of MIB-1, p53, and p21 of organotypic muticellular spheroids (OMS) following cisplatin (CDDP) and irradiation (RT). MATERIAL AND METHODS: Spheroids of the GaMg glioma cell line and OMS prepared from biopsy tissue of six glioblastoma patients were used. Radiochemosensitvity (5 microg/ml CDDP followed by RT) was determined using migration and proliferation assays on CLS. In OMS, histology and immunohistochemical studies of MIB-1, p53, and p21 expression were examined 24 and 48 h following treatment. RESULTS: Combination treatment led to a migration inhibition of 38% (CDDP 13%; RT 27%) and specific growth delay of 2.6 (CDDP 1.3; RT 2.1) in CLS. Cell cycle analysis after combination treatment showed an accumulation of cells in the G2/M phase. In OMS, apoptosis increased, cell proliferation decreased, and p53/p21 expression increased more pronounced following CDDP+RT. No morphological damage was observed. CONCLUSION: CDDP can lead to enhancement of the RT effect in spheroids of both human glioma cell line spheroids and biopsy spheroids from glioblastoma specimens. The exerted effect is additive rather than synergistic.

Dose-effect relationship for radiotherapy after incomplete resection of atypical neurocytomas.

Neurocytomas with atypical histology or high proliferation activity are named atypical. All reported cases were reviewed. After incomplete resection, radiotherapy improved local-control (P<0.001) and survival (P=0.02). Doses (EQD2) >54 Gy were associated with better 5-year local control (84% versus 55%, P=0.05) and 5-year-survival (84% versus 65%, P=0.18) than doses < or =54 Gy.

Well-differentiated neurocytoma: what is the best available treatment?

Most neurocytomas are well differentiated, being associated with better long-term survival than the more aggressive atypical lesions. Atypical neurocytomas are characterized by an MIB-1 labeling index >3% or atypical histologic features. This analysis focuses on well differentiated neurocytomas in order to define the optimal treatment. A case with a follow-up of 132 months is presented. The patient developed two recurrences two and four years after first surgery, each showing an increasing proliferation activity. Furthermore, all published well-differentiated neurocytoma cases were reviewed for surgery, radiotherapy, and prognosis. Additional relevant data were obtained from the authors. Complete resection (CTR), complete resection plus radiotherapy (CTR + RT), incomplete resection (ITR), and incomplete resection plus radiotherapy (ITR + RT) were compared for outcome by using the Kaplan-Meier method and the log-rank test. Data were complete in 301 patients (CTR, 108; CTR + RT, 27; ITR, 81; ITR + RT, 85). Local control and survival were better after CTR than after ITR (P < 0.0001 and P = 0.0085, respectively). Radiotherapy improved local control after ITR (P < 0.0001) and after CTR (P = 0.0474), but not survival (P = 0.17 and P = 1.0, respectively). In the ITR + RT group, doses < or =54 Gy (n = 33) and >54 Gy (n = 32) were not significantly different for local control (P = 0.88) and survival (P = 0.95). The data demonstrated CTR to be superior to ITR for local control and survival. After CTR and ITR, radiotherapy improved local control, but not survival. A radiation dose of 54 Gy appeared sufficient. Application of postoperative radiotherapy should be decided individually, taking into account the risk of local failure, the need for another craniotomy, and potential radiation toxicity.

Reducing the overall treatment time for radiotherapy of metastatic spinal cord compression (MSCC): 3-year results of a prospective observational multi-center study.

BACKGROUND: This prospective multi-center study investigates a reduction of the overall treatment time for radiotherapy of MSCC, which is important for these mostly disabled patients. PATIENTS AND METHODS: Two standard fractionation schedules, 30 Gy/10 fractions/2 weeks (n = 71) and 40 Gy/20 fractions/4 weeks (n = 65) were compared for functional outcome and ambulatory status. Motor function was graded using an 8-point-scale before RT, at the end and at 6, 12 and 24 weeks after RT. A multi-variate analysis was performed for functional outcome. Included variables were the fractionation schedule and the three relevant prognostic factors. These factors are the type of primary tumor, the time of developing motor deficits before RT and the pre-treatment ambulatory status. RESULTS: The ambulatory rates were 49% in the 30 Gy group and 52% in the 40 Gy group before RT (P = 0.888), and 56% and 60% after RT (P = 0.888). Improvement of motor function occurred in 45% of the 30 Gy group and 40% of the 40 Gy group (P = 0.752). The relevant prognostic factors were comparably distributed in both groups. According to the multivariate analysis, a slower development of motor deficits (P < 0.001), a favorable histology (P = 0.040) and being ambulatory (P = 0.045) were associated with better functional outcome, whereas the fractionation schedule had no significant impact (P = 0.311). CONCLUSIONS: The data suggest both schedules to be comparably effective for functional outcome. Thus, 30 Gy/10 fractions/2 weeks should be applied instead of 40 Gy/20 fractions/4 weeks. The reduction of the overall treatment time from 4 to 2 weeks means less discomfort for the paraparetic or paraplegic patient.

Defining the best available treatment for neurocytomas in children.

BACKGROUND: In children, neurocytomas are extremely rare tumors in the central nervous system. Since this entity was introduced in 1982, approximately 60 cases have been reported among patients age /= 54 Gy when compared for local control (P = 1.0) and survival rates (P = 1.0). Radiotherapy-related psychomotor retardation or secondary brain tumors were not reported. CONCLUSIONS: The prognosis of children with neurocytomas is extremely good. CTR was associated with better local control and survival rates than ITR. After ITR, radiotherapy improves local control, but not survival. If postoperative radiotherapy is considered, a dose of 50 Gy was appropriate for long-term local control in children, whereas higher doses were required in adults.

A prospective evaluation of two radiotherapy schedules with 10 versus 20 fractions for the treatment of metastatic spinal cord compression: final results of a multicenter study.

BACKGROUND: The optimal treatment of patients with metastatic spinal cord compression (MSCC) is still being debated. The current observational multicenter study, performed prospectively by the authors, evaluated two radiotherapy (RT) schedules and prognostic factors with respect to functional outcome METHODS: In the current study, 214 patients with MSCC were irradiated between April 2000 and September 2003 with 30 gray (Gy) per 10 fractions per 2 weeks (n = 110) or with 40 Gy per 20 fractions per 4 weeks (n = 104). Motor function and ambulatory status were evaluated before RT and until 6 months after RT. The following potential prognostic factors were investigated: RT schedule, performance status, age, number of irradiated vertebrae, type of primary tumor, pretreatment ambulatory status, and length of time developing motor deficits before RT. RESULTS: Both groups were balanced for patient characteristics and potential prognostic factors. Motor function improved in 43% of patients after 30 Gy and in 41% of patients after 40 Gy (P = 0.799). Posttreatment ambulatory rates were 60% and 64% (P = 0.708), respectively. A multivariate analysis demonstrated that a slower progression of motor deficits before RT (P < 0.001), a favorable histology of the primary tumor (P < 0.001), and being ambulatory before RT (P = 0.035) were associated with a better functional outcome. RT schedule (P = 0.269) and other variables had no significant impact. Acute toxicity was mild, and late toxicity was not observed during the period of follow-up. Follow-up was 12 (6-28) months in patients surviving >/= 6 months. CONCLUSIONS: Thirty gray per 10 fractions was preferable to 40 Gy per 20 fractions, because it was associated with similar outcome, less treatment time, and lower costs. The type of tumor, pretreatment ambulatory status, and length of time developing motor deficits before RT were relevant prognostic factors and should be considered in future studies.

Is there a life-long risk of brachial plexopathy after radiotherapy of supraclavicular lymph nodes in breast cancer patients?

BACKGROUND AND PURPOSE: To contribute to the question whether the risk of radiation-related brachial plexopathy increases, remains constant or decreases with time after treatment. PATIENTS AND METHODS: Between 12/80 and 9/93, 140 breast cancer patients received supraclavicular lymph node irradiation using a telecobalt unit. Total dose was 60 with 3Gy per fraction at a depth of 0.5 cm and 52 with 2.6Gy per fraction to the brachial plexus at a depth of 3 cm. Twenty-eight women received chemotherapy, 34 tamoxifen. Brachial plexopathy was graded using a modified LENT-SOMA score. Actuarial complication-free survival and overall survival were obtained from Kaplan-Meier analysis. The impact of chemotherapy or tamoxifen was tested using the chi2 test. The annual incidence of radiation-related brachial plexopathy was assessed by exponential regression as described by Jung et al. [Radiother Oncol 61 (2001) 233]. RESULTS: Actuarial overall survival was 67.1% after 5 years, 54.0% after 10 years, 49.9% after 15 years, and 44.0% after 20 years. In 19/140 patients, brachial plexopathy grade>/=1 occurred after a median interval of 88 (30-217) months. The percentage of patients being free from plexopathy was 96.1% after 5 years, 75.5% after 10 years, 72.1% after 15 years, and 46.0% after 19 years, respectively. A significant impact of type of surgery, chemotherapy or tamoxifen was not observed. The annual incidence of brachial plexopathy was 2.9% for grade>/=1 lesions and 0.8% for grade>/=3 lesions. The rates did not change significantly with time. CONCLUSIONS: The risk of brachial plexopathy after supraclavicular lymph node irradiation in breast cancer patients remains constant for a considerable portion of the patient's life.

Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients.

BACKGROUND AND PURPOSE: Amifostine has been shown to protect against xerostomia induced by radiotherapy for head and neck cancer, but its impact on the therapeutic index is unknown. This is the first report focusing on amifostine related adverse effects leading to discontinuation of amifostine treatment. PATIENTS AND METHODS: Thirty-nine patients from two centers irradiated for head and neck cancer received i.v.-infusions of amifostine prior to each radiation fraction. In a phase III study, two daily amifostine doses, 200 mg/m(2) (n = 21) and 340 mg/m(2) (n = 18), were compared for protection against radiation induced toxicity. Total radiation dose was 60-70Gy (2Gy per fraction), nine patients received concurrent chemotherapy with cisplatin/5-FU. amifostine was usually discontinued after >1 episode of serious toxicity during subsequent treatment sessions. RESULTS: In 16/39 patients (41%) amifostine was discontinued due to severe adverse effects, which led to discontinuation of the phase III study. In four of 16 patients radiotherapy was delayed due to amifostine related adverse effects for 1-3 days. Discontinuation occurred more often in patients receiving chemotherapy. The results led to a literature review for amifostine treatment during radiotherapy in head and neck cancer patients. Regarding our series and published series using an amifostine schedule comparable to ours, total discontinuation rate was 27% (57/214). Discontinuation was significantly influenced by chemotherapy (P = 0.007) but not by amifostine dose (P = 0.156). CONCLUSION: Daily i.v. administration of amifostine during radiotherapy in head and neck cancer is associated with a high rate of serious adverse effects leading to discontinuation of amifostine treatment and sometimes delay of radiotherapy.

Prognostic value of the MIB-1 labeling index for central neurocytomas.

Although central neurocytomas are generally described as benign CNS lesions, malignant behavior including craniospinal dissemination and tumor-related death may occur. This meta-analysis was performed to investigate the prognostic value of the MIB-1 labeling index. Data were obtained not from the literature alone but also from contact with the authors. The data suggested an MIB-1 index score of >3% to be associated with a worse prognosis for local control (p < 0.0001) and survival (p = 0.0004).