Molecular pathological insights reveal a high number of unfavorable risk patients among children treated for medulloblastoma and CNS-PNET in Oslo 2005-2017.

BACKGROUND: An unexplained regional difference in survival was observed in previous publications on outcome for children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. We aimed now to reevaluate and perform a retrospective molecular-based risk stratification of all embryonal brain tumors (excluding atypical teratoid rhabdoid tumors [ATRT]) in pediatric patients, who underwent surgery and treatment at Oslo University Hospital between 2005 and 2017. PROCEDURE: Specimens from all patients <20 years of age with initial diagnosis of medulloblastoma or CNS-PNET were reviewed. Molecular analyses comprised NanoString gene expression, molecular inversion probe profiling, Sanger sequencing, and 850K-methylation analysis. Whole chromosomal aberration signatures were assessed in standard-risk non-WNT/non-SHH medullobastomas for molecular risk stratification. RESULTS: We identified 53 non-ATRT embryonal tumors among which 33 were medulloblastomas. Molecular genetic parameters including whole chromosomal aberration signatures allowed classification of 17 medulloblastomas as molecular high risk. These patients had a significantly worse 5-year overall survival than the remaining 16 medulloblastoma patients (52.9% vs. 87.1% p = 0.036). Five patients in our cohort had tumors that are considered as new entities in the 2021 classification of tumors of the central nervous system. Five tumors were re-classified as nonembryonal tumors after review. CONCLUSION: Molecular-based risk stratification of standard-risk non-WNT/non-SHH medulloblastoma enabled superior identification of medulloblastomas with dismal prognosis. Our cohort demonstrated a significantly increased fraction of standard-risk non-WNT/non-SHH medulloblastoma with molecular high-risk profile compared to other studies, which might have contributed to previously reported unfavorable outcome data.

Oral and dental late effects in long-term survivors of childhood embryonal brain tumors.

PURPOSE: To investigate oral and dental late effects in survivors of childhood brain tumors medulloblastoma (MB) and central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). METHODS: This cross-sectional study assessed oral and dental late effects in MB/CNS-PNET survivors treated before 20 years of age, and with a minimum of 2 years since treatment. Participants went through an oral and radiographic examination. We assessed oral status using the decayed-missing-filled index (DMFT), oral dryness, maximum mouth opening (MMO), fungal infection, and registration of dental developmental disturbances (DDD) in the form of hypodontia, microdontia, and enamel hypoplasia. RESULTS: The 46 participants' mean age at enrolment was 27 ± 12.8 years and at treatment 8.5 ± 5.2 years, and the mean time since treatment was 18.9 ± 12 years. Over a third (35%) of survivors had reduced mouth opening (mean 29.3 ± 5.6 mm (range 16-35)). A significantly lower MMO was found in individuals treated ≤ 5 years compared to survivors treated > 5 years (p = 0.021). One or more DDD were registered in 30.4% of the survivors, with a significantly higher prevalence in individuals treated ≤ 5 years (p < 0.001). Hypodontia was the most prevalent type of DDD. There was no difference in DMFT score in relation to age at treatment. Oral dryness was not frequently reported or observed in these survivors. CONCLUSION: Survivors of childhood MB/CNS-PNET are at risk of oral and dental late effects including reduced mouth opening and DDD. The risk is highest in survivors treated before the age of 5.

Taste and smell function in long-term survivors after childhood medulloblastoma/CNS-PNET.

PURPOSE: To investigate taste and smell function in survivors, with a minimum of 2 years since treatment of childhood medulloblastoma (MB)/central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). METHODS: This cross-sectional study included 40 survivors treated ≤ 20 years of age. Taste strips with four concentrations of sweet, sour, salt, and bitter were used to assess taste function in all participants. Score from 0 to 16; ≥ 9 normogeusia, < 9 hypogeusia, and complete ageusia which equals no sensation. No sensation of a specific taste quality equals ageusia of that quality. Thirty-two participants conducted smell testing using three subtests of Sniffin' sticks: threshold, discrimination, and identification. Together they yield a TDI-score from 1 to 48; functional anosmia ≤ 16.00, hyposmia > 16.00- < 30.75, normosmia ≥ 30.75- < 41.50, and ≥ 41.50 hyperosmia. Results were compared with normative data. Survivors rated their taste and smell function using a numerical rating scale (NRS) score 0-10. RESULTS: Forty survivors with a mean time since treatment of 20.5 years, 13 (32.5%) were diagnosed with hypogeusia, nine (22.5%) of these being ageusic to one or more taste qualities. Seventeen (53%) of 32 participants were diagnosed with hyposmia. The mean scores of the olfactory subtests, and TDI score were significantly lower than normative data (P < 0.0001). The mean NRS scores of smell and taste function were 7.9 ± 1.5 and 8 ± 1.3, respectively. CONCLUSION: Our study showed impaired taste and smell function in survivors of childhood MB/CNS-PNET using objective measurements. However, subjective ratings did not reflect objective findings.

Outcomes in adulthood after neurosurgical treatment of brain tumors in the first 3 years of life: long-term follow-up of a single consecutive institutional series of 97 patients.

BACKGROUND: Long-term outcome for children who underwent surgery for brain tumors in the first 3 years of life is not well-known. METHODS: We performed a retrospective study on surgical morbidity, mortality rate, academic achievement, and work participation in children below 3 years of age who underwent primary tumor resection for a brain tumor in the period from 1973 to 1998. Gross motor function and activities of daily life were scored according to the Barthel Index. Long-term survivors were defined as with a survival from primary diagnosis of 20 years or more. FINDINGS: Ninety-seven consecutive children were included. No patient was lost to follow-up. Gross total resection was achieved in 67 children during the primary procedure, 25 had subtotal resections, and 5 had only partial resection. The 20-year survival figures for the 46 children with high-grade tumors was 33%, and the corresponding figures for 51 patients treated for low-grade tumors was 82%. Five of the 57 20-year-survivors died 21, 29, 30, 30, and 41 years, respectively, following primary surgery. Fifty of the 52 long-term survivors had a Barthel Index (BI) of 100, while the remaining two had a BI of 40. Twelve patients were long-term survivors after treatment for HG tumors (26%), while 40 of the 51 patients treated for LG tumors (78%) were alive. Thirty-two of the 52 long-term survivors were in full-time work and 29 of them after treatment for LG tumors. Another 10 were in part-time work, while the last 10 individuals had no working capacity. CONCLUSION: Survival is better for patients with low-grade tumors compared with those with high-grade tumors. The functional level of long-term survivors is affected by adjuvant therapy and radiotherapy in particular. Neurosurgical intervention in itself is safe and plausible for pediatric brain tumor patients below 3 years of age. However, there should be a focus on potential late affects, and survivors should be followed by knowledgeable clinical staff for the neoplastic disease as well as for potential side effects. In this consecutive series, a 33% 20-year survival for children treated for HG tumors and 82% for patients with LG tumors was observed. The patients with LG tumors who had been treated with surgical resection without any adjuvant therapy showed a good clinical outcome as adults, and two-thirds of them were in full-time work.

Unmet rehabilitation needs in 86% of Norwegian paediatric embryonal brain tumour survivors.

AIM: To study incidence, types and degrees of late effects in a geographical cohort of paediatric medulloblastoma and central nervous system primitive neuroectodermal tumour (CNS-PNET) survivors, and identify the need for rehabilitation. METHODS: Between 1974 and 2013, 63 patients survived treatment for paediatric medulloblastoma and CNS-PNET at Oslo University Hospital, Norway. Of these, 50 accepted invitation and were included in this study. RESULTS: Median follow-up was 20 years (range 3.2-41), and 96% of participants had developed late effects. Cognitive impairment was found in 72%, reduced hearing in 68%, endocrine deficits in 66%, epilepsy in 32% and another 30% had been diagnosed with one or more second primary neoplasms. Radiotherapy significantly increased risk of secondary primary neoplasms and endocrinological deficits, chemotherapy risk of ototoxicity and endocrinological deficits, and epilepsy was found significantly more often in CNS-PNET than medulloblastoma patients. Epilepsy was the main cause of cognitive impairments (full-scale IQ) in our study. 86% of participants had an unmet rehabilitation need. CONCLUSION: Significant late effects and unmet rehabilitation needs were documented in the large majority of survivors after treatment for paediatric medulloblastoma and CNS-PNET.

Children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor in Norway from 1974 through 2013: Unexplainable regional differences in survival.

BACKGROUND: A previous study based on Norwegian Cancer Registry data suggested regional differences in overall survival (OS) after treatment for medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. The purpose of the present study was to confirm in an extended cohort whether there were regional differences in outcome or not, and if so try to identify possible explanations. MATERIAL AND METHODS: Data from patients aged 0-20 years diagnosed with and treated for MB/CNS-PNET at all four university hospitals in Norway from 1974 to 2013 were collected and compared. RESULTS: Of 266 identified patients, 251 fulfilled inclusion criteria. MB was diagnosed in 200 and CNS-PNET in 51 patients. Five-year OS and event-free survival (EFS) were 59% and 52%, respectively. There was a significant difference in five-year OS and EFS between MB and CNS-PNET patients; 62% versus 47% (P =  0.007) and 57% versus 35% (P < 0.001). In multivariable analysis, two factors were found to significantly contribute to improved five-year OS and EFS, whereas one factor contributed to improved five-year OS only. Gross total resection (GTR) versus non-GTR (hazard ratio [HR] 0.53, P =  0.003; HR 0.46, P < 0.001) and cerebrospinal irradiation (CSI) versus non-CSI (HR 0.24, P < 0.001; HR 0.28, P < 0.001) for both, and treatment outside Oslo University Hospital for OS only (HR 0.64, P =  0.048). CONCLUSION: Survival was comparable with data from other population-based studies, and the importance of GTR and CSI was confirmed. The cause for regional survival differences could not be identified.

Adult outcome after neurosurgical treatment of brain tumours in the first year of life: long-term follow-up of a single consecutive institutional series of 34 patients.

BACKGROUND: Long-term results for adult patients who underwent surgery for paediatric brain tumours in the first year of life have not been reported. METHODS: We performed a retrospective study on surgical morbidity, mortality rate, academic achievement and/or work participation in patients who underwent primary tumour resection for a brain tumour as infants in the period from 1973 to 1998. Gross motor function and activities of daily life were scored according to the Barthel Index. FINDINGS: Thirty-four consecutive children were included. No patient was lost to follow-up. Twenty-two children (65%) underwent gross total resection (GTR), 10 had subtotal resections (STR) and 2 had only partial resection during primary surgery. Nine children were additionally surgically treated for hydrocephalus (HC), many of them with repeat operations for shunt malfunction during follow-up. Three children died within 30 days following GTR of highly vascular tumours. Seventeen (50%) of the infants had high-grade tumours with 1-month, 1-year and 20-year survival figures of 88, 30 and 30%. The corresponding figures for 17 patients treated for low-grade tumours were 94%, 88% and 88%, respectively. Seventeen patients (50%) are still alive as adult long-term survivors at median age of 29 years (range 20 to 43 years). Three died after 29, 30 and 41 years, respectively. At the latest follow-up, 16 out of 17 long-term survivors have a Barthel Index (BI) of 100, while the remaining one has a BI of 40. Two long-term survivors of a high-grade tumour treated 30 and 35 years ago are severely handicapped and have no working capacity. The 15 long-term survivors after treatment for a low-grade tumour are all in daily activity as students (4), in part-time work (3) or full-time work (8). CONCLUSION: A brain tumour occurring in the first year of life is a serious threat to the patient and the family, particularly in case of high-grade tumours. In our small cohort, the results from long-term survivors of high-grade tumour group are depressing and confirm the deleterious effect of radiotherapy given to infants decades ago. The infants with low-grade tumours who could be treated with surgical resection without any adjuvant therapy show a good clinical outcome as adults. For parents of these latter patients, the results are far better than feared in advance.

Neurosurgical treatment of gangliogliomas in children and adolescents: long-term follow-up of a single-institution series of 32 patients.

OBJECT: The object of this study was to delineate long-term results of the surgical treatment of pediatric tumors classified as ganglioglioma or gangliocytoma. METHODS: A cohort of consecutive patients 19 years or younger who had undergone primary resection of CNS tumors during the years 1980-2016 at a single institution were reviewed in this retrospective study of surgical morbidity, mortality, and academic achievement and/or work participation. Gross motor function and activities of daily living were scored using the Barthel Index (BI). RESULTS: Patient records for 32 consecutive children and adolescents who had undergone resection for a ganglioglioma were included in this study. Of the 32 patients, 13 were in the first decade at the first surgery, whereas 19 were in the second decade. The male/female ratio was 1.0 (16/16). No patient was lost to follow-up. The tumor was localized to the supratentorial compartment in 26 patients, to the posterior fossa in 5 patients, and to the spinal cord in 1 patient. Only two of the tumors were classified as anaplastic. Of the 30 low-grade tumors, 2 were classified as gangliocytomas, 6 were desmoplastic infantile gangliogliomas, and 22 were ordinary gangliogliomas. The aim of primary surgery was gross-total resection (GTR) and was achieved in 23 patients (71.9%). Altogether, 43 tumor resections were performed. Eight patients underwent a second resection from 1 to 10 years after primary surgery and three of these also had a third resection from 2 to 24 years after initial surgery. The reason for further resection was clinical (seizure control failure/recurrence of epilepsy or progressive neurological deficit) and/or residual tumor progression/recurrence. There was no operative mortality in this series and all 32 patients are alive with follow-up periods from 0.5 to 36 years (median 14 years). Observed 14-year survival is thus 100%. One out of two children with primary anaplastic tumor received local radiotherapy (proton) postoperatively. The other 31 patients did not have any kind of non-surgical adjuvant therapy. Twenty-one out of 26 children with supratentorial tumor had epilepsy as one of their presenting symptoms. Nineteen of these became seizure-free after initial surgery (18 of them after GTR), but 3 patients experienced recurrence of seizures within some years. Functional outcome in terms of ADL, schooling, and work participation was gratifying in most patients. Five patients have persistent hydrocephalus (HC), treated with ventriculoperitoneal (VP) shunts. CONCLUSION: Low-grade gangliogliomas (GGs) can be surgically treated with good long-term results including seizure and tumor control as well as school and working participation.

Outcome for children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor (CNS-PNET) - a retrospective analysis spanning 40 years of treatment.

BACKGROUND: Medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor of the central nervous system (CNS-PNET) are among the most common pediatric brain tumors. The diagnosis, treatment, and outcome of MB/CNS-PNET patients treated during the last four decades at Oslo University Hospital (OUH) are described. MATERIAL AND METHODS: All patients younger than 20 years of age diagnosed and treated for MB/CNS-PNET at OUH between 1 January 1974 and 31 December 2013 were identified. RESULTS: We found 175 patients. In 13 of them, the diagnosis was changed upon histopathological review and in 4 patients part of the treatment was administered at other hospitals. Thus, 158 patients were included for further analysis. Eight patients did not receive adjuvant therapy because of a dismal clinical condition. The overall 5-year survival rate for MB and CNS-PNET was 54%, for MB 57%, and for CNS-PNET 41%. Gross total resection (GTR) was achieved in 118 patients and 5-year overall survival for patients with GTR versus those with non-GTR differed significantly with 64% versus 22%. Cytological examination of the cerebrospinal fluid was performed in 52 patients. A total of 126 patients received radiotherapy as part of the primary treatment and 24 did not due to young age. Median time from surgery to start of radiotherapy was 33 days. Duration of radiotherapy was more than 48 days in 22% of patients. At the time of analysis, 63 patients were alive and disease-free, one alive with disease, and 94 patients were deceased; 84 of these due to MB/CNS-PNET and 10 due to supposed late effects from the treatment. CONCLUSIONS: Survival was comparable to data from other population-based studies. The importance of GTR for survival was corroborated. Reporting real-world data remains crucial to know the true outcome of patients treated outside clinical trials.

Neurosurgical treatment of brain tumors in the first 6 months of life: long-term follow-up of a single consecutive institutional series of 30 patients.

OBJECT: The aim of this study is to delineate the long-term results for patients going through surgery for pediatric brain tumors in the first 6 months of life. METHODS: Thirty consecutive children (1-182 days old) who underwent primary resection for a brain tumor during the years 1973-2012 were included in this retrospective study on surgical morbidity, mortality rate, academic achievement, and/or work participation. Gross motor function and activities of daily life were scored according to the Barthel index. RESULTS: Of the 30 patients, 11 children had surgery in the first 3 months of life (1 to 88 days) and 19 were aged 3 to 6 months (94-182 days) at the time of surgery. The male/female ratio was 1.0 (15/15). No patients were lost to follow-up. Two patients died in the postoperative period (30 days). Another eight patients died during the follow-up. Twenty patients are alive, with follow-up times from 2 to 38 years, median 13 years. Among the 28 children who survived the primary resection, eight underwent repeat surgery from 6 months to 5 years after the first operation. Two children were operated three times, and one of these also a fourth time. Gross total resection (GTR) was achieved in 20 of the primary resections, subtotal resection (STR) in 6, and in the last 4, only a biopsy or a partial resection was performed. Nine children received adjuvant chemotherapy and three of these also radiotherapy (in the years 1979-1987). Among the 20 survivors, the Barthel index is normal (100) in 18 patients, 40 in one, and 20 in the last one. Eight tumors were located to the posterior fossa, and 22 were supratentorial. Eighteen tumors were histologically low-grade (WHO grade I-II), most of these were plexus papillomas (7) or astrocytomas (7), and 12 were high-grade (WHO grade III-IV); PNET/medulloblastomas (6), ependymoma (2), glioblastoma (2), teratoma, and plexus carcinoma. CONCLUSION: Infants with brain tumors may clearly benefit from surgical resection with favorable results even for prolonged periods of time. Ten children died, two of them with prolonged survival for 9 and 29 years. Among the 20 survivors, a stable very long-term result appears obtainable in 18 also when it comes to quality of life. Four of the survivors have been treated for highly malignant tumors with a follow-up of 5, 11, 14, and 26 years. One of our infant patients treated for GBM in 1982, lived for 29 years, however, with a progressive decline in the quality of life probably due to postoperative whole-brain radiation.

Neuropsychological functioning in survivors of childhood medulloblastoma/CNS-PNET: The role of secondary medical complications.

Objective To investigate the long-term cognitive consequences of malignant pediatric brain tumor and its treatment, and factors explaining variability in cognitive functioning among survivors. Method: A geographical cohort of survivors of pediatric medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS-PNET), treated between 1974 and 2013, was invited to participate. Of the 63 surviving patients, 50 (79%) consented to participation. The participants were tested with a battery of neuropsychological tests covering a wide age range. Verbal cognition, nonverbal cognition, processing speed, attention, memory, executive functioning, and manual dexterity were assessed. The participants were between 5:5 and 51:11 years of age at time of assessment. Assessments took place on average 19 years after primary tumor resective surgery. Results: One participant had a severe intellectual disability. For the rest, IQ varied from 52 to 125, with a mean score of 88.0 (SD 19.7). Twenty-eight (56%) of the participants had full-scale IQ scores in the age-average range or above. Gender, age at operation, time since operation, the presence of secondary medical complications, and treatment variables explained 46% of the variability in IQ scores, F(4,44) = 9.5, p<.001. The presence of endocrine insufficiency in combination with either epilepsy and/or hydrocephalus was associated with lowered IQ, lowered processing speed, and memory impairments. Conclusion: Patients treated for childhood MB and CNS-PNET have a lifelong risk of medical sequelae, including impaired cognitive functioning. This study adds to the literature by demonstrating the importance of following neuropsychological functioning closely, especially processing speed, learning, and memory, in survivors who have multiple secondary medical complications.

Bone mineral density and nutrition in long-term survivors of childhood brain tumors.

BACKGROUND AND AIMS: Childhood cancer survivors are at risk of unwanted late effects. The primary aim of this study was to assess bone mineral density Z-scores (BMDz) in long-term survivors of childhood medulloblastoma (MB) or central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). Secondary aims were to describe nutrient intake, vitamin D status, physical activity and explore potential risk factors for decreased BMDz. METHODS: All MB and CNS-PNET survivors treated at Oslo University Hospital from 1974 to 2013 were invited to participate in a cross-sectional study. Dual-energy x-ray absorptiometry (Lunar Prodigy) assessed BMDz lumbar spine, BMDz total body, and lean body mass. Decreased BMDz was defined as a combination of low BMDz -1 to -1.99 and very low BMDz ≤-2. Lean body mass index (LMI) was calculated by dividing lean body mass by the squared height. Nutrient intake was assessed by a 3-day food record. Serum 25(OH)D was analyzed. Physical activity was reported by a questionnaire. Descriptive statistics and multivariable Cox regression analyses were applied. RESULTS: Fifty survivors with a median age of 25.5 years (5.5-51.9) and a median follow-up time of 19.5 years (3.2-40.5) were included. Mean BMDz lumbar spine was -0.8 (SD 1.1, 95% CI: -1.1 to -0.4), and BMDz total body was -0.6 (SD 1.1, 95% CI: -0.9 to -0.3). Decreased BMDz was detected in 48% of the lumbar spine and 34% of the total body measurements. In all, 62% had low calcium, and 69% had low vitamin D intake. 26% of participants had serum 25(OH)D < 50 nmol/L, and 62% reported an inactive lifestyle. Male sex, higher age at diagnosis, and lower LMI were potential risk factors for decreased BMDz. CONCLUSIONS: Long-term survivors of childhood MB and CNS-PNET had decreased BMDz, and risk factors were male sex, higher age at diagnosis, and lower LMI. Inadequate calcium and vitamin D intake, an inactive lifestyle, and a high prevalence of 25(OH)D ≤ 50 nmol/L were detected.

Fertility-preserving measures for girls and young women with cancer.

BACKGROUND: Children and young adults with cancer may be rendered infertile as a result of their treatment. The purpose of this article is to provide an overview of fertility-preserving measures for girls and young women. MATERIAL AND METHODS: The article is based on literature searches in the medical databases Medline, Pubmed and Scopus and the experience of a Nordic cooperative group on gonadal preservation in connection with cancer treatment. RESULTS: There are several methods for preserving the fertility of girls and young women with cancer. These should form a part of the actual cancer treatment. Cryopreservation of embryos is a well established method for adult cancer patients, also in Norway. Cryopreservation of eggs and ovarian tissue is to be regarded as still at the experimental stage. Research and new methods will improve the options for prepubertal children and young adults with disseminated cancer. INTERPRETATION: Multidisciplinary cooperation is necessary to ensure that children and young cancer patients receive thorough information about the risk of infertility after cancer treatment, and about potential fertility-preserving measures.

Fertility-preserving measures for boys and young men with cancer.

BACKGROUND: Some types of cancer treatment entail a risk of reduced fertility and infertility. Fertility-preserving treatment can reduce the risk for some. The purpose of this article is to provide an overview of the risk of infertility after treatment of boys and young men with cancer and of fertility-preserving measures. MATERIAL AND METHODS: The article is based on literature searches in the medical databases Medline, Pubmed and Scopus and on the experience of a Nordic medical network collaboration. RESULTS: Cryopreservation of sperm is an established method for adult cancer patients in Norway. Vibratory stimulation of the penis and electroejaculation with subsequent freezing of sperm may be an option for young cancer patients who cannot manage to produce a semen sample with the aid of masturbation. Freezing of testicular biopsies may be an option for prepubertal boys who are not capable of producing mature sperm. INTERPRETATION: There are established methods for cryopreservation of sperm for adult cancer patients. The other fertility-preserving measures for boys and young men with cancer are regarded as experimental at present.

Long-term outcome of posterior fossa medulloblastoma in patients surviving more than 20 years following primary treatment in childhood.

The aim of the study was to analyze the long-term outcome (>20 years) after treatment of posterior fossa medulloblastoma (MB) in childhood. We analyzed data from patients treated for posterior fossa MB between 1974 (introduction of the first international treatment protocol in Norway) and 1987 (when use of radiotherapy was abandoned in children under 4 years of age). Out of 47 children, 24 survived >20 years. At the time of analysis, 16 patients (median age 41 years, range 32-52) were alive (median follow-up 34 years, range 30-42), while 8 patients died 22-41 years (median 31 years) after primary treatment: one late death (after 22 years) was due to tumor recurrence whilst other 7 deaths (after 23 to 41 years) were related to the detrimental effects of the treatment (secondary tumors, stroke, severe epilepsy and depression). Observed 20- and 30-year survival rates were 51% and 44%, respectively. Despite successful treatment of MB in childhood and satisfactory tumor control during the first 20 years following primary treatment, our data indicates that even long-term survivors may die from tumor recurrence. However, the main factors causing late mortality and morbidity in long-term survivors seem to be the complications related to radiotherapy given in childhood.

Neurosurgical treatment of pediatric pleomorphic xanthoastrocytomas: long-term follow-up of a single-institution, consecutive series of 12 patients.

OBJECTIVEThe authors conducted a study to delineate the long-term results of the surgical treatment of pediatric pleomorphic xanthoastrocytomas (PXAs).METHODSAll consecutive children and adolescents (0-20 years) who underwent primary tumor resection for a PXA during the years 1972-2015 were included in this retrospective study on surgical morbidity, mortality rate, academic achievement, and/or work participation. Gross motor function and activities of daily living were scored according to the Barthel Index.RESULTSOf the 12 patients, 8 patients were in the 1st decade of life and 4 in the 2nd. The male/female ratio was 6:6. No patient was lost to follow-up. One patient presented with severe progressive tumor disease and died within 3 months after repeated resection. Another child died 3 days following a second surgical procedure involving gross-total resection (GTR) 8 years after the initial operation. The other 10 patients were alive at the latest follow-up when they reached the median age of 34 years (range 11-60 years). The median follow-up duration was 22 years (range 2-41 years). Barthel Index score was 100 in all 10 survivors. A total 18 tumor resections were performed. Five patients underwent a second tumor resection after MRI/CT confirmed recurrent tumor disease, from 6 months up to 17 years after the initial operation. Only one of our patients received adjuvant therapy: a 19-year-old male who underwent resection (GTR) for a right-sided temporal tumor in 1976. This particular tumor was originally classified as astrocytoma WHO grade IV, and postoperative radiotherapy (54 Gy) was given. The histology was reclassified to that of a PXA. Seven of 8 children whose primary tumor resection was performed more than 20 years ago are alive as of this writing-i.e., 88% observed 20-year survival. These are long-term survivors with good clinical function and all are in full- or part-time work.CONCLUSIONSPediatric patients with PXA can be treated with resection alone with rewarding results. Recurrences are not uncommon, but repeated surgery is well tolerated and should be considered in low-grade cases before adjuvant therapy is implemented. Follow-up including repeated MRI is important during the first postoperative years, since individual patients may have a more aggressive tumor course.

Posterior fossa ependymoblastoma diagnosed in the second month of life: uneventful 12 years survival after gross total resection followed by chemotherapy.

We report on an infant who underwent gross total resection (GTR) of a posterior fossa ependymoblastoma in the second month of life followed by chemotherapy with uneventful long-term survival for 12 years. Postoperative radiotherapy has been considered obligate to have a chance for prolonged survival, but is inadvisable in infants. To our knowledge, this is the first reported long-term survival in an infant treated for ependymoblastoma.

Neurosurgical treatment of pediatric low-grade midbrain tumors: a single consecutive institutional series of 15 patients.

OBJECT: The authors delineate the long-term results of surgical treatment for pediatric low-grade midbrain glioma. METHODS: A series of 15 consecutive patients (age range 0-15 years) who underwent primary tumor resection for a low-grade midbrain glioma during the years 1989-2010 were included in this retrospective study on surgical morbidity, mortality rate, academic achievement, and/or work participation. Gross motor function and activities of daily living were scored according to the Barthel Index. RESULTS: Of the 15 patients, 10 were in their 1st decade (age 0-9 years) and 5 were in their 2nd decade of life (age 10-15 years) at the time of surgery. The male/female ratio was 0.50 (5:10). No patients were lost to follow-up. One patient died in the postoperative period (32 days posttreatment). Another 2 patients died during follow-up. One patient succumbed to acute bleeding in the resection cavity 8 months after surgery, and the other died of shunt failure 21 years after initial treatment. Twelve patients are alive at the time of this writing, with follow-up periods from 3 to 24 years (median 8 years). Among the 12 survivors, the Barthel Index scores were normal (100) in 11 patients and 80 in 1 patient. A total of 25 tumor resections were performed. In 1 patient, further resection was performed 5 days after initial resection due to MRI-confirmed residual tumor. Another 5 patients underwent repeat tumor resection after MRI-confirmed progressive tumor disease and clinical deterioration ranging from 3 months to 4 years after the initial operation. Three of these 5 patients also underwent a third resection, and 1 of the 3 underwent a fourth operation. Six children received adjuvant therapy: local radiotherapy in 2 patients, chemotherapy in 3 patients, and both in 1 patient. Twelve (80%) of the 15 patients needed treatment for persistent hydrocephalus. CONCLUSIONS: Selected cases of low-grade midbrain gliomas may clearly benefit from resection with favorable results, even for prolonged periods. Three patients in the present series died, one of whom had a prolonged survival period of 21 years. Among the 12 survivors, stable long-term results appeared obtainable in at least 9. One patient died of acute hemorrhage 8 months after initial resection; otherwise, rapid tumor progression and death were not observed. Forty percent of the patients received adjuvant treatment, with local radiotherapy, chemotherapy, or both.

Neurosurgical treatment of oligodendroglial tumors in children and adolescents: a single-institution series of 35 consecutive patients.

OBJECT: The object of this study was to delineate long-term results of the surgical treatment of pediatric CNS tumors classified as oligodendroglioma (OD) or oligoastrocytoma (OA) WHO Grade II or III. METHODS: A cohort of 45 consecutive patients 19 years or younger who had undergone primary resection of CNS tumors originally described as oligodendroglial during the years 1970-2009 at a single institution were reviewed in this retrospective study of surgical morbidity, mortality, and academic achievement and/or work participation. Gross motor function and activities of daily living were scored using the Barthel Index (BI). RESULTS: Patient records for 35 consecutive children and adolescents who had undergone resection for an OA (17 patients) or OD (18 patients) were included in this study. Of the 35 patients, 12 were in the 1st decade of life at the first surgery, whereas 23 were in the 2nd decade. The male/female ratio was 1.19 (19/16). No patient was lost to follow-up. The tumor was localized to the supratentorial compartment in 33 patients, the posterior fossa in 1 patient, and the cervical medulla in 1 patient. Twenty-four tumors were considered to be WHO Grade II, and 11 were classified as WHO Grade III. Among these latter lesions were 2 tumors initially classified as WHO Grade II and later reclassified as WHO Grade III following repeat surgery. Fifty-four tumor resections were performed. Two patients underwent repeat tumor resection within 5 days of the initial procedure, after MRI confirmed residual tumor. Another 10 patients underwent a second resection because of clinical deterioration and progressive disease at time points ranging from 1 month to 10 years after the initial operation. Six patients underwent a third resection, and 1 patient underwent a fourth excision following tumor dissemination to the spinal canal. Sixteen (46%) of the 35 children received adjuvant therapy: 7, fractionated radiotherapy; 4, chemotherapy; and 5, both fractionated radiotherapy and chemotherapy. One patient with primary supratentorial disease experienced clinically malignant development with widespread intraspinal dissemination 9 years after initial treatment. Only 2 patients needed treatment for persistent hydrocephalus. In this series there was no surgical mortality, which was defined as death within 30 days of resection. However, 12 patients in the study, with follow-up times from 1 month to 33 years, died. Twenty-three patients, with follow-up times from 4 to 31 years, remained alive. Among these survivors, the BI was 100 (normal) in 22 patients and 80 in 1 patient. Nineteen patients had full- or part-time work or were in normal school programs. CONCLUSIONS: Pediatric oligodendroglial tumors are mainly localized to the supratentorial compartment and more often occur in the 2nd decade of life rather than the 1st. Two-thirds of the patients remained alive after follow-ups from 4 to 31 years. Twelve children succumbed to their disease, 9 of them within 3 years of resection despite combined treatment with radio- and chemotherapy. Three of them remained alive from 9 to 33 years after primary resection. Among the 23 survivors, a stable, very long-term result was attainable in at least 20. Five-, 10-, 20-, and 30-year overall survival in patients with Grade II tumors was 92%, 92%, 92%, and 88%, respectively.

Febrile neutropenia in children with cancer: a retrospective Norwegian multicentre study of clinical and microbiological outcome.

Our objective was to describe clinical and laboratory characteristics, treatment and outcome among Norwegian children with cancer suffering from chemotherapy-induced febrile neutropenia (FN). We retrospectively reviewed data on paediatric FN episodes in 7 Norwegian hospitals during a 2.5-y period. A total of 236 episodes of FN occurred in 95 children. Acute lymphoblastic leukaemia was the most common diagnosis (49 patients). Blood cultures yielded growth in 39 episodes (17%). Primary empirical antibiotic regimens could be assigned to 2 main groups: 1) benzylpenicillin or ampicillin and an aminoglycoside (58%) or 2) a regimen based on third-generation cephalosporins (42%). There were no statistically significant differences in outcome between the 2 regimens in terms of need to change initial antibiotic treatment, d of fever or maximum C-reactive protein values. One infection-related death (fungal septicaemia) occurred during the study period. We conclude that incidence of septicaemia and clinical outcome is similar to recent international trials on paediatric FN, but antibiotic treatment in Norway differs from international guidelines. However, patients in our study were successfully and safely treated, irrespective of the primary empirical antibiotic regimen.