Perinatal (fetal and neonatal) astrocytoma: a review

Introduction

The purpose of this review is to document the various types of astrocytoma that occur in the fetus and neonate, their locations, initial findings, pathology, and outcome. Data are presented that show which patients are likely to survive or benefit from treatment compared with those who are unlikely to respond.

Materials and methods

One hundred one fetal and neonatal tumors were collected from the literature for study.

Results

Macrocephaly and an intracranial mass were the most common initial findings. Overall, hydrocephalus and intracranial hemorrhage were next. Glioblastoma (GBM) was the most common neoplasm followed in order by subependymal giant cell astrocytoma (SEGA), low-grade astrocytoma, anaplastic astrocytoma, and desmoplastic infantile astrocytoma (DIA). Tumors were detected most often toward the end of the third trimester of pregnancy.

Conclusion

A number of patients were considered inoperable since their tumor occupied much of the intracranial cavity involving large areas of the brain. High-grade astrocytomas were more common than low-grade ones in this review. Fetuses and neonates with astrocytoma have a mixed prognosis ranging from as low as 20 % (GBM) to a high of 90 %. The overall survival was 47/101 or 46 %.

     

Evaluating extent of resection in pediatric glioblastoma: a multiple propensity score-adjusted population-based analysis

Purpose

The benefit of radical resections for glioblastoma patients remains a source of contention in the literature. Few studies have been conducted in pediatric patients, and it is becoming increasingly evident that data regarding adult glioblastoma (GB) patients cannot be generalized to pediatric patients affected by this neoplasm. A comparative effectiveness study is performed for different extent of resection (EOR) groups in the largest cohort of pediatric GB (pGB) patients.

Methods

The Surveillance, Epidemiology, and End Results (SEER) cancer registry was used to identify pGB patients from 1988 through 2009. Multivariate- and multiple propensity score (mPS)-adjusted analyses were used to determine the effect of gross total resection (GTR), partial resection (PR), and biopsy (Bx) on overall survival. Survival prospects were summarized using direct adjusted survival curves.

Results

A total of 342 pGB patients were identified, and 35.4 % of patients received a GTR, 28.8 % PR, 17.3 % Bx, and 17.0 % did not undergo surgery. In our cohort, a median overall survival of 12 months was observed with 1-, 2-, and 5-year survival rates of 51.7, 28.3, and 15.7 %, respectively. EOR was a predictor of survival in both the multivariate- (P < 0.001) and mPS-adjusted model (P < 0.001). Compared to the GTR group, a higher mortality rate was observed in patients who underwent a PR (HR 1.50; 95 % CI, 1.02–2.21) or Bx (HR 1.87; 95 % CI, 1.18–2.98). There were no significant differences in (adjusted) mortality risk between the PR and Bx groups.

Conclusion

Our study suggests that GTR is independently associated with improved survival for pediatric patients with glioblastoma.

     

Second primary brain tumors following cranial irradiation for pediatric solid brain tumors

Purpose

We describe our institution’s experience with seven patients who developed second brain tumors following cranial irradiation.

Methods

The median age at first irradiation was 8 years (range, 3–20 years). Initial diagnoses were two cases of germinoma, one non-germinomatous germ cell tumor (NGGCT), three cases of medulloblastoma, and one pineal gland tumor (pathology undetermined). All patients received craniospinal irradiation followed by local boost and the median dose to the initial tumor area was 54.0 Gy (range, 49.8–60.6 Gy). Four patients (two medulloblastomas, one germinoma, and one NGGCT) received chemotherapy.

Results

Second brain tumors were diagnosed a median of 114 months (range, 64–203) after initial radiation. Pathologic diagnoses were one glioblastoma, two cases of anaplastic astrocytoma, one medulloblastoma, one low-grade glioma, one high-grade glial tumor, and one atypical meningioma. Five patients underwent surgical resection with subsequent radiotherapy. One anaplastic astrocytoma patient received chemotherapy only following stereotactic biopsy. The meningioma patient was alive 32 months after total resection and radiosurgery for subsequent recurrences. Six patients died within 18 months and most deaths were due to disease progression.

Conclusions

Most patients diagnosed with second brain tumors had received high-dose, large-volume radiotherapy with chemotherapy at a young age. Further studies are required to determine the relationship between radiotherapy/chemotherapy and the development of secondary brain tumors.     

Pediatric glioblastoma: a single institution experience

Purpose

The aim of this study was to evaluate characteristics of childhood glioblastoma multiforme, effectiveness of treatment modalities, and detect factors related to outcome.

Methods

A detailed analysis was performed on a series of 15 patients treated between 2000 and 2013, based on their clinical, radiologic, pathologic, treatment, and follow-up data.

Results

Median survival time of children with glioblastoma was 13.5 months. One- and 2-year overall survival probabilities were 66.7 and 20 %, respectively. There were no significant differences in survival based on patients’ gender, age, disease presentation with or without epileptic seizures, signs/symptoms of increased intracranial pressure, or tumor location. The presence of neurological deficit initially, as well as prior to radiotherapy, which was quantified by neurologic function score (NFS), had an impact on overall survival. Children with NFS 0 lived longer compared to others (p?=?0.001). Survival of children that underwent gross total resection was longer than that of children that underwent subtotal resection (p?=?0.030). Mean survival time of children with gross total resection was 73.5 months, compared to 13 months in children with subtotal resection. There was no significant correlation between outcome and type of radiotherapy. In four patients with gigantocellular glioblastoma, we found no evidence of a better prognosis. Two long-term survivors were recorded. Both of them underwent gross total resection and were assigned a NFS 0.

Conclusions

Gross total resection is essential for longer overall survival among pediatric patients with glioblastoma and offers a possibility for long-term survival. Severity of neurologic symptoms quantified by NFS can be considered as a potential predictor of outcome.

     

Treatment and outcomes of primary intracranial teratoma

Purpose

Until recently, postoperative adjuvant treatment for intracranial teratomas has remained controversial because of the rarity of the tumors and the heterogeneity of histologic types. To define optimal therapy modalities, we retrospectively analyzed the treatment of patients with intracranial teratomas.

Methods

Between 1979 and 2007, 31 patients with intracranial teratomas were treated at our institution. The median age of the 31 patients was 14.8 years. The median follow-up time was 72.7 months (range 11～291 months). Perioperative radiochemotherapy was done in 19 patients. Proper chemotherapy regimens were followed, such as PE (cisplatin and VP-16), PVB (cisplatin, VP-16, and bleomycin), ICE (carboplatin, VP-16, and ifosfamide), and NGGCT (etoposide, carboplatin, bleomycin, and cyclophosphamide with mesna).

Results

Eight patients experienced recurrence, and a second operation was carried out in six patients. Fifteen patients survived for more than 5 years without recurrence, irrespective of having received adjuvant therapies. The 5-year survival rate of the 31 patients was 74%.

Conclusion

Treatment of intracranial teratomas is very difficult because of the heterogeneity of the tumor cells from totipotent origins. Accurate histological diagnosis of teratoma subtypes is the most important factor for adequate treatment, and proper therapeutic protocols are needed to cure teratomas.

     

Pre-radiation chemotherapy improves survival in pediatric diffuse intrinsic pontine gliomas

Background

The median survival of patients with diffuse intrinsic pontine glioma (DIPG) remains less than 1 year. The BSG 98 pre-irradiation chemotherapy protocol showed a significant increase in overall survival. In contrast to current treatment strategies, patients did not have to undergo surgical stereotactic biopsy, which can sometimes lead to complications, to be included in this protocol.

Materials and methods

We retrospectively reviewed all the cases of DIPG that were treated in our department from September 15, 2004 to September 15, 2014. We compared the group of patients who followed our BSG 98 protocol to those who were treated with new targeted therapy protocols where systematic biopsy was required.

Results

Patients in the BSG 98 protocol were treated with BCNU, cisplatin, and methotrexate, followed by radiation at disease progression. Targeted therapy protocols included radiation therapy along with treatment by erlotinib, cilengitide, or an association of nimotuzumab and vinblastine. Sixteen patients were treated with the BSG 98 protocol, and 9 patients were treated with new targeted therapy protocols. Median overall survival was significantly higher in the BSG 98 group compared to the targeted therapy group (16.1 months (95 % CI, 10.4–19.0) vs 8.8 months (95 % CI 1.4–12.3); p?=?0.0003). An increase in the median progression-free survival was observed (respectively, 8.6 vs 3.0 months; p?=?0.113).

Conclusion

The present study confirms that the BSG 98 protocol is one of the most effective current treatment strategies for DIPG. It may be used as the control arm in randomized trials investigating the use of innovative treatments and may be proposed to families who are averse to biopsy.

     

Pediatric diffuse intrinsic pontine glioma patients from a single center

Background

The prognosis of children with diffuse intrinsic pontine gliomas (DIPG) is dismal. This study aims to evaluate the characteristics and treatment outcome of children with DIPG in a single center.

Methods

We reviewed the outcome of children with DIPG treated at the Oncology Institute of Istanbul University from February 1999 to May 2012.

Results

Fifty children (26 female, 24 male) with the median age of 7 years were analyzed. The median duration of symptoms was 30 days. All patients received radiotherapy (RT). Before the year 2000, 12 patients received only RT. Thirty-eight had concomitant and/or adjuvant chemotherapy with RT. Between 2000 and 2004, 17 patients received cis-platinum or vincristine as sensitizers during RT and CCNU + vincristine combination after RT. Since 2004, 21 patients received temozolomide (TMZ) concomitantly during RT and as adjuvant chemotherapy after RT. The median survival time of all patients was 13 months (1–160 months). Patients receiving RT + TMZ had a significantly higher overall survival than patients with only RT (p?=?0.018). Patients receiving RT + chemotherapy other than TMZ also had a significantly higher overall survival than patients receiving only RT (p?=?0.013). Patients receiving RT + TMZ + and chemotherapy other than TMZ had a significantly higher survival than patients receiving only RT (p?=?0.005).

Conclusion

In our series, patients receiving RT + TMZ and also patients receiving RT + chemotherapy other than TMZ had a significantly higher overall survival than patients treated with only RT. Hence, administering chemotherapy during and after RT seems to prolong survival in some DIPG patients.     

Association between the growth rate of subependymal giant cell astrocytoma and age in patients with tuberous sclerosis complex

Purpose

The most common neurological complications associated with tuberous sclerosis complex (TSC) include intractable seizures that begin in infancy and subependymal giant cell astrocytoma (SEGA) complicated by hydrocephalus with increasing age. Information on SEGA growth of TSC patients is limited. This study aimed to examine the TSC-SEGA growth rates by periodic neuroimaging.

Methods

This study evaluated the TSC-SEGA growth rates by serial neuroimaging. Fifty-eight patients with TSC underwent systematic evaluation, including a review of medical history and serial brain neuroimaging.

Results

While magnetic resonance imaging was more sensitive in detecting cortical tubers than computed tomography (73.1 vs. 0 %, p?<?0.001), its efficacy in identifying intracranial lesions was comparable to that of computed tomography (96.2 vs. 100 %, p?=?0.658). Significant tumor growth was observed in children (p?=?0.012) and adults (p?=?0.028) during follow-up periods, respectively (median for children 23.5 months, interquartile range 18–40 months and median for adults 23 months, interquartile range 12–34 months). Further, the SEGA growth rate in children was significantly higher than that in adults (75.6 vs. 16.5 %, p?=?0.03).

Conclusions

The results of the study show that SEGA has a significantly higher growth rate in children using serial follow-up brain imaging, suggesting the importance of performing follow-up neuroimaging at yearly intervals in childhood to identify and prevent potential comorbidities.

     

Functional Improvement Among Intracerebral Hemorrhage (ICH) Survivors up to 12 Months Post-injury

Background and Purpose

As survival rates have increased for intracerebral hemorrhage (ICH) patients, there is limited information regarding recovery beyond 3–6 months. This study was conducted to examine recovery curves using the modified Rankin Scale (mRS) and Barthel Index (BI) up to 12 months post-injury.

Methods

We prospectively enrolled 173 patients admitted with ICH who were subsequently evaluated using the mRS and BI at discharge as well as 3, 6, and 12 months. Repeated measures nonparametric testing was conducted to assess functional trajectories across time.

Results

The mRS scores showed significant improvement between discharge (median 4) and 3 (median 4), 6 (median 4), and 12 months (median 3) (p values <0.001). However, the mRS scores did not differ between follow-up time-points (i.e., 3–6, 6–12 months). There was significant improvement in scores using the BI (p values <0.001), showing improvement between discharge (mean 43.0) and 3 (mean 73.0), 6 (mean 78.2), and 12 months (mean 83.4). Additionally, there were differences in the BI between 3 and 12 months (p = 0.013), as well as between 6 and 12 months (p = 0.025).

Conclusions

The BI may be a more sensitive measure of long-term recovery post-injury than the mRS, which shows minimal improvement for some survivors after 3 months. BI scores indicate survivors continually improve till 12 months post-injury. These results may have implications for the prognostication of ICH and design of clinical trial outcome measures.

     

Pilocytic astrocytoma with anaplastic features presenting good long-term clinical course after surgery alone: a case report

Purpose

Pilocytic astrocytomas (PAs) are the most common brain tumor in children and typically have an excellent prognosis. However, some PAs show histologically anaplastic features. It is reported that PAs with anaplastic features often need the postoperative radiation and chemotherapy due to aggressiveness such as early local recurrence and dissemination. We describe an interesting case of primary anaplastic PA with good clinical course in the long-term.

Methods

A 10-year-old man presented with worsening headache and vomiting. Magnetic resonance imaging (MRI) showed a large cystic tumor with contrast-enhanced solid component in a right occipital lobe. Magnetic resonance spectroscopy (MRS) showed the decrease of N-acetylaspartate (NAA) and the increase of choline and lipids, which suggested the malignancy.

Results

The patient was operated with an occipital lobectomy. The tumor was incompletely resected due to the deep invasion to the inner wall of lateral ventricle. Pathological diagnosis was a pilocystic astrocytoma with anaplastic features. Although aggressive features were suspected from magnetic resonance spectroscopy and pathological findings, the remnant tumor showed no recurrence for 8 years without any postoperative treatments.

Conclusion

PAs could exhibit variable behavior, and careful managements including wait-and-scan should be considered, because adjuvant therapies may cause child’s growth disorder and malignant transformation.

     

A Self-Regulatory Intervention for Patients with Head and Neck Cancer: Pilot Randomized Trial

Background

Research is yet to investigate whether psychological interventions delivered early after diagnosis can benefit patients with head and neck cancer (HNC).

Purpose

The aim of this study was to investigate the effectiveness of a brief self-regulatory intervention (targeting illness perceptions and coping) at improving HNC patient health-related quality of life (HRQL).

Methods

A pilot randomized controlled trial was conducted, in which 64 patients were assigned to receive three sessions with a health psychologist in addition to standard care or standard care alone. Participants completed questionnaires assessing HRQL, general distress, and illness perceptions at baseline and again 3 and 6 months later.

Results

Compared to the control group, patients who received the intervention had increased treatment control perceptions at 3 months (p = .01), and increased social quality of life at 6 months (p = .01). The intervention was particularly helpful for patients exhibiting distress at baseline.

Conclusion

A brief psychological intervention following HNC diagnosis can improve patient perceptions of treatment and social quality of life over time. Such interventions could be targeted to patients who are distressed in order to confer the greatest benefit.

Trial Registration Number

12614000813684.

     

The postirradiation incidence of cavernous angioma is higher in patients with childhood pineoblastoma or primitive neuroectodermal tumors than medulloblastoma

Purpose

The purpose of this study is to investigate the incidence of cavernous angioma (CVA) in long-term survivors of childhood embryonal tumors treated by cranial irradiation.

Materials and methods

Between 1990 and 2012, we treated 25 patients (13 males, 12 females) with embryonal tumors (17 medulloblastomas, 5 primitive neuroectodermal tumors (PNET), 3 pineoblastomas) with craniospinal irradiation. Follow-up ranged from 15.5 to 289.9 months, the irradiation dose to the whole neural axis from 18 to 36 Gy, and the total local dose from 49.6 to 60 Gy. All patients underwent follow-up magnetic resonance imaging (MRI) studies at least once a year, and the diagnosis of posttreatment CVA was based solely on MRI findings.

Results

At the time of this writing, 18 were alive and free of the recurrence of the original disease or the development of secondary neoplasms other than CVA; another 2 were alive with medulloblastoma or diffuse astrocytoma. Posttreatment, 14 patients developed CVAs in the course of a median of 56.7 months; 13 of these presented with multiple CVAs. Patients who underwent radiation therapy (RT) at an age younger than 6 years developed multiple CVAs significantly earlier than those treated at a later age (p?=?0.0110). Patients with PNET or pineoblastoma developed Zabramski type 1 and 2 CVA significantly earlier than did medulloblastoma patients (p?=?0.0042).

Conclusion

We attribute the high rate of post-RT CVA in our long-term follow-up study of pediatric patients to the delivery of cranial irradiation for embryonal tumors, especially PNET and pineoblastoma, and recommend the regular, long-term follow-up of patients whose embryonal tumors were treated by cranial irradiation.

     

Pilot study of enhanced social support with automated telephone monitoring after psychiatric hospitalization for depression

Background

Following discharge, patients hospitalized for depression are at high risk for poor retention in outpatient care and adverse outcomes.

Aims

Pilot tests a post-hospital monitoring and enhanced support program for depression.

Method

48 patients at a Veterans Affairs Medical Center discharged following a depression-related inpatient stay received weekly visits or phone calls for 6 months from their choice of either a family member/friend (n = 19) or a certified peer support specialist (n = 29). Participants also completed weekly automated telephone monitoring calls assessing depressive symptoms and antidepressant medication adherence.

Results

Over 90% of participants were more satisfied with their care due to the service. The mean change from baseline to 6 months in depression symptoms was ?7.9 (p < 0.05) according to the Patient Health Questionnaire and ?11.2 (p < 0.05) according to the Beck Depression Inventory-II for those supported by a family member/friend, whereas those supported by a peer specialist had mean changes of ?3.5 (p < 0.05) and ?1.7 (p > 0.10), respectively.

Conclusions

Increased contact with a chosen support person coupled with automated telephone monitoring after psychiatric hospitalization is an acceptable service for patients with depression. Those who received the service, and particularly those supported by a family member/friend, experienced reductions in symptoms of depression.

     

Palliative Care Consultations in the Neuro-ICU: A Qualitative Study

Background

Integration of palliative care (PC) into the neurological intensive care unit (neuro-ICU) is increasingly recommended, but evidence regarding the best practice is lacking. We conducted a qualitative analysis exploring current practices and key themes of specialist PC consultations in patients admitted to a single neuro-ICU.

Methods

We retrospectively identified all patients who were admitted to the neuro-ICU for ≥24 h and received a PC consultation between January and August 2014. We reviewed PC consultation notes and neuro-ICU progress notes from the electronic health records of these patients. We performed content analysis on the PC notes.

Results

Twenty-five neuro-ICU patients (4 %) received a PC consultation over 8 months with the most prevalent reason of clarifying goals of care. The main distinctions between patients with and those without (n = 580) a PC consultation were ICU length of stay (median 8.2 vs. 2.8 days) and death in the neuro-ICU (56 % vs. 11 %). The most prevalent themes addressed in the PC consultation notes were (1) discussing prognosis, (2) eliciting patient and family values, (3) understanding medical options, and (4) identifying conflict.

Conclusions

PC consultations in the neuro-ICU emphasize family coping and decision-making by helping discuss prognosis and exploring patient and family values as well as their ability to understand the medical information. Several features suggest that earlier integration of PC into neuro-ICU care may enhance both coping and the decision-making process.

     

Daten zum aktuellen Praxiseinsatz von Eslicarbazepinacetat in Deutschland

Background

The anticonvulsant eslicarbazepine acetate (ESL) is licensed as adjunctive therapy for adults with partial-onset seizures (POS).

Objectives

To gather information on the use of ESL in current clinical practice in Germany and to assess its efficacy and tolerability.

Methods

Clinical data from consecutive patients with POS who started adjunctive treatment with ESL after 1 January 2012 was retrospectively collected from 18 neurological centres in Germany. Data on utilisation, efficacy, and tolerability of ESL were documented on a standardised electronic documentation sheet.

Results

Included in the analysis were 125 patients (median age: 48 years (range 20–83 years), 59.2?% male). The most common primary treatment goals were improvement of seizure control (70.4?% of patients) and improvement of tolerability (20.8?%). A median dose of 800 mg (range 400–2,400 mg) was both the initial target and last treatment dose. The responder rate, defined as proportion of patients achieving a reduction in seizure frequency by ≥50?% versus baseline, was 46.7?%, 53.3?%, and 55.3?% after 3, 6, and 12 months, respectively. At the last documented visit, 38.8?% of patients were seizure-free for ≥3 months. The last documented visit occurred after a mean treatment period of 397 ± 246 days. The physician’s rating of ESL efficacy was very good or good in 61.6?% of treated patients, while tolerability was rated very good or good in 70.4?% of patients. Due to adverse events (AEs), 12.0?% of patients discontinued treatment with ESL. More frequently (≥5?%) reported AEs were fatigue, dizziness, and hyponatremia. Overall, 77?% of patients continued ESL therapy for at least 12 months.

Conclusions

In this retrospective collection of current real-life data in Germany, adjunctive anticonvulsant treatment with ESL was effective and well-tolerated.

     

Onset of bladder and motor symptoms in multiple system atrophy: differences according to phenotype

Purpose

To compare the order of presentation of bladder and motor symptoms between multiple system atrophy phenotypes.

Methods

Medical records were retrospectively reviewed in 144 patients.

Results

Bladder symptoms occurred either before or within 12 months after onset of motor symptoms in significantly more patients with the cerebellar phenotype than the parkinsonian phenotype (80 vs. 53%, p = 0.003); similar results were observed for urinary incontinence (79 vs. 45%, p = 0.001).

Conclusions

Urinary dysfunction is more likely to appear either before or shortly after motor symptoms in the cerebellar phenotype than in the parkinsonian phenotype.

     

Management of Elderly Patients with Glioblastoma

Purpose of Review

Glioblastoma represents one of the major challenges in neurooncology and approximately half of the patients are 60 years or older. We summarize the particular situation of elderly glioblastoma patients with a focus on therapeutic considerations.

Recent Findings

Favorable molecular markers such as mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes are virtually absent in glioblastomas in elderly patients. Treatment options are similar to the situation in young patients and comprise surgical resection, radiation therapy, and alkylating chemotherapy. The performance status as well as comorbidities may have a stronger impact on the individual treatment decision than in young patients. The MGMT promoter methylation status allows for a stratification of treatment beyond the surgical intervention. In patients with MGMT promoter methylated tumors, monotherapy with temozolomide is superior to radiotherapy alone. Similarly, the benefit conferred by combined temozolomide-based chemoradiotherapy compared to radiotherapy alone is largely restricted to patients with MGMT promoter-methylated tumors. At recurrence, no standard treatment has been established.

Summary

The prognosis for elderly patients with glioblastoma remains poor. The MGMT promoter methylation status helps guiding treatment decisions and withholding inactive, but potentially harmful treatments.