Craniotomy for brain metastases: a consecutive series of 316 patients.

OBJECTIVE: To assess the incidence of craniotomy for brain metastases, overall survival (OS), surgical mortality, and prognostic factors in a large, contemporary, consecutive series from a well-defined catchment area. MATERIAL AND METHODS: All patients ≥ 18 years who underwent craniotomies for intracranial metastases at Oslo University Hospital, Rikshospitalet and Ullevål, between 2005 and June 30, 2009 were included (n = 316). Patients were identified from our prospectively collected database and a thorough review of all charts to validate the entered data was performed. RESULTS: The annual incidence of first-time craniotomy for a brain metastasis was 2.6/100,000 inhabitants. Patient age ranged from 25 to 87 years (median 64 years). The 30-day mortality rate was 3.8%. Median OS was 9.2 months. Recursive partitioning analysis was class I in 19.6%, class II in 59.2%, and class III in 21.2% with median OS of 16.2, 8.9, and 5.6 months, respectively (P < 0.001). Lung cancer and melanoma were associated with a higher risk (>1% per year) of developing brain metastases. Significant negative prognostic factors were age ≥ 65, a poor performance score, unstable extracranial disease, presence of extracranial metastases, multiplicity, metastasis in eloquent area, and no post-operative radiotherapy. CONCLUSIONS: In this population study, the annual incidence of a first-time craniotomy for a brain metastasis was 2.6/100,000, the 30-day mortality rate was 3.8%, and median OS was 9.2 months. The well-known prognostic factors were confirmed.

Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme.

OBJECTIVES: To study overall survival (OS), prognostic factors, and repeated surgery in glioblastoma multiforme (GBM). MATERIAL AND METHODS: Retrospective study of 516 consecutive adult patients who underwent primary surgery for a GBM in year 2003-2008. RESULTS: Median age at primary surgery was 63.7 years (range 18.0-88.0). Median OS was 9.9 months. Age > 60 years, poor preoperative ECOG score, bilateral tumor, biopsy rather than resection, and no temozolomide chemoradiotherapy were negative risk factors. Repeat surgery was performed in 65 patients (13%). Median time between first and second surgery was 7 months. Indications for second surgery were increasing neurological deficits (35.4%), raised ICP (33.8%), asymptomatic but reoperated because of tumor progression verified on MRI (20.0%), and epileptic seizures (11%). Patients who underwent repeated surgery had longer OS; 18.4 months vs 8.6 months (P < 0.001). CONCLUSIONS: OS for adult GBM patients was 9.9 months. Negative prognostic factors were increasing age, poor neurological function, bilateral tumor involvement, biopsy instead of resection, and RT alone compared to temozolomide chemoradiotherapy. Our rate of repeated surgery for GBM was 13% and the main indications for second surgery were raised ICP and increasing neurological deficits. In a carefully selected group of patients, repeat surgery significantly prolongs OS.

Prevalence of Norwegian patients diagnosed with childhood cancer, their working ability and need of health insurance benefits.

The object of this study was in a population-based material to investigate the prevalence of patients diagnosed with childhood cancer, and compared to the general population to assess working ability, yearly income and need for health insurance benefits in patients surviving at least five years after treatment for childhood CNS tumours or hematological malignancies. During the period January 1, 1970 to December 31, 2002 the prevalence in the Norwegian population of patients diagnosed with any childhood cancer increased from 12.2 (473/3 888 305) to 65.1 (2944/4 524 066) per 100 000 population. The proportion of survivors in need of any health insurance benefit was for CNS tumours 47.1% and for hematological malignancies 21.0%. The proportion in the age group 16-67 receiving disability pension for CNS tumours was 94/454 (20.7%) compared to 21/575 (3.7%) for patients treated for hematological malignancies (p < 0.001). Of patients given radiotherapy 25/70 (35.7%) received disability pension, compared to 90/959 (9.4%) in unirradiated patients, p < 0.001. Yearly income and working ability was particularly low for CNS tumour survivors. This study illustrates loss of working capability associated with pediatric cancer and treatment and long-term requirement of health insurance benefits.

Impact of intraoperative MRI on the surgical results for high-grade gliomas.

OBJECTIVE: The impact of intraoperative MRI (iMRI) on the surgical procedure, patient outcome and median survival for a series of patients harbouring high-grade gliomas forms the basis of this study. Their outcome has been compared to a matched cohort of patients operated in a conventional manner to determine if the use of intraoperative MRI can be shown to improve the results of surgery and prognosis for this type of patient. MATERIALS AND METHODS: 32 microsurgical open craniotomies, performed in the intraoperative iMRI scanner for grade IV supratentorial gliomas, with follow-up periods of more than 2 months, were analyzed for this study. A group of 32 primary high-grade glioma patients (no recurrent tumors) were matched for age, preoperative clinical grade, gender and histology and operated during a corresponding time interval in a conventional manner acted as controls. RESULTS: All 64 patients were examined and analyzed for the occurrence of postoperative increased neurological morbidity or death. No complications directly related to the intraoperative scanning procedures were observed and no intraoperative death occurred in either group. The average operating time in the intraoperative scanner was 5.1 hours and was significantly longer than in the conventional OR (3.4 hours). The mean overall survival time for the 32 patients in the study group was 14.5 months (95 % confidence interval 12.0 - 16.6) compared to 12.1 months (95 % confidence interval 10.2 - 14.1) for the matched control group. CONCLUSION: Although iMRI is an effective way of imaging residual tumor, this study could not demonstrate an increased efficacy of surgery utilizing this technique for patients harbouring grade IV gliomas compared to more conventional methods. No statistical significance was noted between the two groups (p = 0.14). The complication rate was within the range reported for other series, in both control as well as the study group.

Trends in incidence of brain and central nervous system tumors in Norway, 1970-1999.

The aim of this study was to investigate trends in the incidence of childhood and adult brain and central nervous system (CNS) tumors in Norway from 1970 through 1999. In this period, a total of 14,641 patients were diagnosed with a primary benign or malignant neoplasm of the brain and CNS. Age-adjusted incidence rates were reported together with results of loglinear regression and an age-period-cohort model based on the Poisson regression model. In children (<15 years), the proportion of brain and CNS tumors was 28.2% (1,042/3,697) of all new cancer cases compared with 2.8% in adults (13,599/492,237). The overall rate of brain and CNS tumors increased during the study period from 6.49 to 12.02 cases per 100,000 person-years. A trend of leveling off in incidence of most tumor categories during the study period was indicated with a possible continuing increase in the period 1995-1999, especially in the age group 0-4 years and in patients aged 60 years or more. Age and period together provided a satisfactory model in patients being <60 years of age and less completeness of diagnosis was found in males compared with females, possibly due to the distribution in males of more aggressive tumors.

Cause of death and long-term survival in patients with neuro-epithelial brain tumours: a population-based study.

Long-term survivors of neuro-epithelial brain tumours have a higher death rate compared with the general population and the aims of this study were to investigate the causes of death and analyse long-term survival using population-based material. A total of 6209 patients were registered in the period of 1970-1993 with a primary intracranial neuro-epithelial tumour in the The Norwegian Cancer Registry. In a pilot study, a high level of agreement with regard to the cause of death was found between clinical data and the registered cause of death. Underlying causes of death in the whole population were therefore analysed. Most deaths were caused by the primary neuro-epithelial brain tumour within 10 years of diagnosis. Although the numbers were small, the proportion of patients dying from other cancers, vascular disease, infections and accidents continued to rise with time. Survival was computed using the Kaplan-Meier method. For children, survival at 5, 10 and 15 years significantly improved from the time period of 1970-1981 to 1982-1993 (47.9, 43.6 and 43.3% versus 63.8, 59.8 and 59.8%, respectively, P <0.0001). Similar improvements in survival at 5, 10 and 15 years were observed for young adults aged 15-49 years (32.7, 21.3 and 16.5% versus 50.1, 37.5 and 33.1%, for the same time periods, P<0.0001). No such improvement for those aged 50 years and over was observed (corresponding figures of 6.6, 3.8 and 2.8% versus 7.7, 4.8 and 3.4%). Prognosis for those with childhood medulloblastomas improved significantly, as did the prognosis of younger adults with low-grade gliomas and unbiopsied/ unclassifiable grade gliomas.

Central nervous system involvement following diagnosis of non-Hodgkin's lymphoma: a risk model.

BACKGROUND: To determine the incidence and risk factors for central nervous system (CNS) relapse in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patient records were registered prospectively in successive patients with NHL admitted to the Norwegian Radium Hospital from 1980 to 1996. A total of 2514 patients had no CNS involvement at diagnosis and were treated according to standard protocols. The incidence and risk factors for CNS progression or relapse were examined retrospectively. RESULTS: In low-grade (L)-NHL, the risk of CNS involvement was low (2.8%). In high-grade (H)-NHL, lymphoblastic and Burkitt's NHL patients had a high risk of CNS recurrence (24.4%) at 5 years, and prophylaxis seemed to reduce this risk. For the other patients with H-NHL, the proportion with CNS involvement at 5 years was 5.2%. Multivariate analysis identified five independent risk factors, each present in >5% of patients: elevated serum lactate dehydrogenase, serum albumin <35 g/l, <60 years of age, retroperitoneal lymph node involvement and involvement of more than one extranodal site. If four or five of these risk factors were present, the risk of CNS recurrence was in excess of 25% at 5 years. CONCLUSIONS: The risk of CNS involvement in this study is comparable with the results from other large series. CNS prophylaxis is not recommended in any subgroup of L-NHL. The risk of CNS involvement among patients with either Burkitt's or lymphoblastic lymphomas is considerable and these patients should therefore receive intensive chemotherapy including systemic and intrathecal methotrexate. Patients with other types of H-NHL should receive adequate CNS prophylaxis if at least four of the five risk factors identified are present.

Ependymoma in children and young adults (0-19 years): report of 25 consecutive cases.

The objective of this retrospective study was to evaluate the relative effect of surgery and radiotherapy (RT) on the survival of 25 consecutive children and young adults treated for ependymoma [18 in the posterior fossa (PF), 2 in supratentorial locations (ST) and 5 in intraspinal locations (IS)]. Five-year survival rates for patients with PF, ST and IS tumors were 28%, 0% and 100%, respectively. Total tumor resection was a positive prognostic factor in the case of PF tumors. No patients with subtotal removal of a PF tumor survived for longer than 5 years. The effect of RT on survival of patients with PF ependymomas in this series was uncertain. No patients with PF ependymoma had disseminated disease at diagnosis, and all tumor recurrences were local. Based on these observations, we see no indications for craniospinal RT of PF ependymomas, except in rare cases of disseminated disease. If RT is given, it should only be targeted to the tumor site. The two patients with ST ependymoma died within 3.8 years after primary treatment. Our series of ST ependymomas does not allow any specific treatment recommendations. One patient with IS ependymoma was cured by surgery alone. Four patients with IS ependymoma had documented residual tumor after surgery. RT induced remission in these patients. For IS ependymomas we recommend no RT if total tumor removal can be documented. In patients with subtotal removal of IS ependymomas local RT is effective and should be given.

Prognostic factors in 140 adult patients with non-Hodgkin's lymphoma with systemic central nervous system (CNS) involvement. A single centre analysis.

We examined retrospectively the outcome of patients with non-Hodgkin's lymphoma (NHL) with systemic involvement of the central nervous system (CNS) registered at The Norwegian Radium Hospital (NRH) from 1980 to 1996, in order to evaluate our treatment strategy for these patients. 170 of 2561 patients (6.6%) had CNS involvement, 140 (5.5%) systemic CNS lymphoma (SCNSL) and 30 (1.2%) primary CNS lymphoma (PCNSL). Description of the patients, time of SCNSL diagnosis, symptoms at CNS diagnosis, treatment and survival were registered. The overall median survival for the 140 patients with SCNSL was 2.6 months (95% confidence interval (CI) 2.1-3.2), only 12 patients are alive in complete remission (CR). Patients with CNS involvement at diagnosis, relapse or progression during treatment for NHL had a median survival of 5.4 months (95% CI: 0.3-10.6), 3.8 months (95% CI: 0.0-9.1), and 1.8 months (95% CI: 1.0-2. 7), respectively (P=0.001). 5 of the 8 patients consolidated with high-dose therapy (HDT) are in CR. Paresis was the only symptom that predicted survival for SCNSL. Patients above 60 years of age with CNS involvement at progression or relapse and those with paresis at the time of CNS diagnosis have a dismal prognosis. For these patients supportive therapy only should be considered. For patients under 60 years of age with chemosensitive disease, the trend was toward better prospects, and they should be offered intensive chemo-radiotherapy including HDT with autologous stem cell support.

[Long-term survival following surgery and radiotherapy of brain tumors in childhood]. / Langtidsoverlevelse etter kirurgi og strålebehandling av hjernesvulster i barnealder.

BACKGROUND: Brain tumours are seen in about one third of children with neoplastic disease. Treatment usually includes surgery and/or radiotherapy. Radiotherapy may have serious late effects, especially in children under the age of three; but is necessary for survival in children with medulloblastomas or high-grade gliomas. MATERIALS AND METHODS: We report ten and 20 years survival rates in 115 children with primary brain tumours (58 medulloblastoma, 14 high-grade gliomas, and 43 low-grade gliomas) operated at the National Hospital and given radiotherapy at the Norwegian Radium Hospital during the years 1970-1995. RESULTS: No patients with medulloblastomas or high-grade gliomas relapsed after ten years. Overall ten and 20 years survival in children treated with radiotherapy to tumour doses > 50 Gy for medulloblastoma was 51.5% and for high-grade gliomas 20%. Median survival for patients with low-grade gliomas was not reached at 20 years, but these patients were still at risk for late deaths. INTERPRETATION: Long-term survival in children with high-grade gliomas or medulloblastoma equals cure, while late relapses may occur in low-grade gliomas.

Stage I high-grade non-Hodgkin's lymphoma.

We report long-term survival and prognostic factors in 252 patients with stage I high-grade lymphoma. Median patient age was 64 years and 49% of patients had extranodal lymphoma. Premenopausal women had less risk of extranodal lymphoma than older women or males (p < 0.002). Disease specific 5 and 15 years' survival in patients < 64 years was 83% and 76%, respectively; compared to 54% and 46% in patients > 64 years of age. Age, non-centroblastic histology, B-symptoms, and increased serum lactate dehydrogenase (LDH) were independently negative prognostic factors (p < 0.01), while extranodal, testicular, or bulky ( > 6 cm) lymphoma presentation were of no prognostic significance. A radiation dose of 40 Gy in 2 Gy fractions to the primary site prevented in-field relapse in 159 of 173 irradiated patients (92%) and only three of 173 patients (1.7%) had local relapse in the absence of systemic dissemination.

An indwelling brachytherapy balloon catheter: potential use as an intracranial light applicator for photodynamic therapy.

An indwelling balloon applicator developed for postoperative intracavity afterloading brachytherapy was evaluated for photodynamic therapy (PDT). Following tumor resection, the applicator is positioned in the center of the resultant cavity and the balloon is inflated with a scattering solution. The liquid-filled balloon stabilizes the resection cavity ensuring a constant and simple geometric shape during treatment. The catheter is brought out through the skin and adjusted so that 1-2 cm projects above the scalp surface. Measurements of light distribution in a phantom model surrounding the balloon catheter, show that it may be used to deliver sufficiently uniform light doses during PDT. The light distribution is uniform to within 5% when the balloon is filled with a scattering medium. Based on simple assumptions, it is shown that the applicator can be used to deliver a sufficient optical dose to brain tissue at a depth of 1 cm in less than 1 h. The applicator has already been used for brachytherapy in 72 patients with few complications. A new treatment protocol employing the combination of both fractionated intracavity brachytherapy and PDT is currently being planned.

Pretreatment factors predict overall survival for patients with low-grade glioma: a recursive partitioning analysis.

PURPOSE: Three databases were pooled and analyzed to determine which groupings of prognostic factors best predicted overall survival for patients with low-grade gliomas treated with surgery and immediate or delayed radiotherapy. METHODS AND MATERIALS: Databases of patients with low-grade gliomas compiled at the London Regional Cancer Centre (LRCC), the Norwegian Radium Hospital (NRH), and the University of California, San Francisco (UCSF) were merged. Inclusion criteria for the pooled analysis included: age > or =18 years and histologically confirmed low-grade (World Health Organization Grade II) supratentorial fibrillary astrocytoma, oligodendroglioma or mixed oligoastrocytoma. Factors analyzed for prognostic significance included: age at diagnosis, gender, seizures at presentation, presence of enhancement on computed tomography (CT) or magnetic resonance imaging (MRI), Karnofsky Performance Status (KPS) at diagnosis, histology, extent of surgical resection, timing of radiotherapy, and treating institution. Univariate and multivariate analysis of overall survival for these factors was performed. Recursive partitioning was performed to generate prognostic groups using these factors. RESULTS: From the combined databases, 401 patients were eligible for analysis. Median survival for the entire group was 95 months/7.9 years. On univariate analysis age 18-40, presence of seizures at presentation, KPS > or =70, treating institution, and absence of contrast enhancement were associated with improved overall survival. On multivariate analysis, these factors remained independent predictors of improved overall survival. Recursive partitioning analysis yielded four prognostic groups with statistically different median survivals (MS): Group I (n = 41: KPS <70, age >40) MS 12 months; Group II (n = 34: KPS > or =70, age >40, enhancement present) MS 46 months; Group III (n = 138: KPS <70, age 18-40 or KPS > or =70 age >40, no enhancement) MS 87 months; Group IV (n = 188: KPS > or =70, age 18-40) MS 128 months. CONCLUSION: Clusters of pretreatment prognostic factors described subgroups of low-grade glioma patients with divergent overall survivals. Consideration of these prognostic subgroups may be important when considering timing of interventions for these patients and in the stratification of patients for clinical trials.

Posterior fossa medulloblastoma in children and young adults (0-19 years): survival and performance.

The objective of this study was to present survival data and outcome status in the long-term survivors of a consecutive series of 111 children and young adults treated for posterior fossa medulloblastoma in our departments from 1960 to 1997. The total surgical mortality was 13%. The surgical mortality rate declined significantly during the time period overall, from 23% before 1970 to 0% after 1990. The 5-year survival rate for patients treated between 1960 and 1973 was 0%, while 5-year survival for patients treated after the introduction of systematic craniospinal radiation in 1974 was 53%. Thirty-four patients were alive at the close of this study, with a mean observation time of 13.5 years. Over half, 61%, of the patients had one or more major deficits/problems with respect to learning ability, power of locomotion, sociability, hobbies and relationships with the opposite sex. A younger age at the time of treatment was correlated with larger deficits/problems in these variables. The correlation between young age at the time of treatment and short final height was significant. The frequency of a second neoplasm was 14%. In all but 3 cases the major cause of permanent deficits/problems was radiation therapy.

Intracavity fractionated balloon brachytherapy in glioblastoma.

In order to reduce hospitalisation time for patients receiving postoperative radiotherapy a phase I-II study of intracavity balloon brachytherapy was instituted. An indwelling balloon catheter was implanted during the closing phase of the initial operation. Starting on the second or third postoperative day the catheter was afterloaded with a high dose rate isotope via a remotely controlled afterloading system. The treatment consisted of 10-12 fractions over a period of 5-6 days, with each treatment session requiring approximately 15 minutes. No external beam radiation was given. Forty-four newly diagnosed patients were treated. A total dose of either 60 Gy (33 patients) or 72 Gy (11 patients) was given. The overall median survival was 11.7 months, (range 2.7-50.9). The treatment was well tolerated and none of the applicators were removed prematurely. The total median hospital stay for this group of patients was significantly reduced compared to more conventional protocols. This study indicates that intracavity high dose rate balloon brachytherapy can achieve survival rates equivalent to those of conventional radiotherapy and is both cost and time efficient.

Prevalence and prognostic significance of epilepsy in patients with gliomas.

The aim of this study was to evaluate the prevalence and prognostic significance of epilepsy in 1028 patients diagnosed in the computer tomography (CT) era with histological low- or high-grade intracranial gliomas. Survival analysis included Kaplan-Meier plots, log-rank tests, logistic regression and Cox's analysis as implemented in the SPSS statistical package. Epilepsy was a positive univariate (P < 0.0001) and multivariate, (P < 0.03) prognostic factor for survival in the total patient group (n = 1028, relative risk of death 0.83, 95% confidence interval (CI) 0.70-0.98) as well as in the high-grade patient group (n = 649, relative risk of death 0.80, 95% CI 0.66-0.96), but not in the group of low-grade glioma patients (P > 0.2). The prevalence of epilepsy in glioblastoma patients was 251/512 (49%), 95/137 (69%) in anaplastic gliomas, and 322/379 (85%) in patients with low-grade gliomas, with 97 of the 102 T1 low-grade subgroup (95%) having epilepsy, indicating that the presence of epilepsy may select patients for early radiological diagnosis. The frequency of epilepsy at presentation decreased with age in high-grade glioma patients, and increased with age in low-grade glioma patients to a plateau in the fourth decade of life (P < 0.01). The prevalence of epilepsy in patients with histological intracranial gliomas varied with patient age and tumour histology, with low-grade patients having the highest prevalence. Epilepsy was a significant positive prognostic factor except in patients with low-grade gliomas, and may select low-grade patients for early diagnosis.

Prognostic significance of CT contrast enhancement within histological subgroups of intracranial glioma.

UNLABELLED: We report the prognostic significance of tumor CT contrast enhancement within histological subgroups in 831 consecutive adult glioma patients of high-grade (n = 516) and low-grade (n = 315) histology. In the present report, a negative prognostic factor is associated with shortened survival. METHODS: Survival analysis including Kaplan-Meier plots, log-rank tests, Cox analysis, and Aalen's linear model as implemented in SPSS and S-PLUS. RESULTS: Sensitivity and specificity of contrast enhancement as a test for high-grade glioma was 0.87 and 0.79, respectively. Enhancement was a strong negative prognostic factor comparable to high-grade histology in the total patient population. Enhancement was also a negative prognostic factor within the subgroups adult high-grade (Grade 3-4), anaplastic (Grade 3), and low-grade (Grade 1-2) gliomas (p < 0.001). The prognostic implications of initial enhancement declined in high-grade patients surviving beyond 36 months. Tumor contrast enhancement or calcifications (in parentheses) were present in 96% (3.6%) of glioblastomas, in 87% (7.4%) of high-grade gliomas, in 56.5% of anaplastic gliomas, and in 21% (16.2%) of low-grade gliomas. Calcification was a positive prognostic factor within the high-grade group of patients (p < 0.0001). CONCLUSION: Enhancement was a major prognostic factor comparable to high-grade histology in this glioma patient population. Enhancement was a negative prognostic factor within each of the adult subgroups high-grade, anaplastic (grade 3), and low-grade gliomas. Enhancement was strongly associated with but not pathognomonic for high-grade histology.

A retrospective study of the value of chemotherapy as adjuvant therapy to surgery and radiotherapy in grade 3 and 4 gliomas.

The aim of this retrospective study was to evaluate the effect of adjuvant chemotherapy among patients < 55 years of age with anaplastic gliomas (historical grade 3, n = 85) with four cycles 4 weeks apart of 160 mg carmustine (BCNU) infused into the internal carotid artery, combined with vincristine 2 mg and procarbazine 50 mg x 3 for 1 week (i.a.BCNU-PV) versus no adjuvant chemotherapy. In glioblastomas (histological grade 4, n = 257) the same chemotherapy was evaluated versus two cycles 4 weeks apart of 160 mg lomustine (CCNU) orally instead of BCNU, combined with vincristine and procarbazine (PCV) versus no chemotherapy. All patients in both groups received radiotherapy. Among glioblastoma patients < 55 years of age there was a significant (P = 0.03), but moderately increased survival in the i.a.BCNU-PV group versus the two other arms that did not differ from each other. This difference could be explained by an uneven distribution of prognostic factors, especially age group (< 50 years versus 50-54 years) in favour of the i.a.BCNU-PV group. In anaplastic gliomas, the median survival in the i.a.BCNU-PV group was 80 months versus 25 months for the no chemotherapy arm (P = 0.004). No significant differences in the distribution of prognostic factors were found between the two therapy arms. We suggest that the role of adjuvant chemotherapy in glioblastomas is unclear, while i.a.BCNU-PV as adjuvant chemotherapy among patients < 55 years of age and with anaplastic gliomas increased survival markedly.