Clinical outcome of surgically treated low-grade gliomas: A retrospective analysis of a single institute

Objective

Low grade gliomas (LGGs) are slow-growing primary brain tumors with heterogeneous clinical behaviors. The aim of our study is to review the treatment outcome of 63 patients with LGGs focusing on surgical outcome and the current therapeutic strategy.

Methods

We retrospectively enrolled 63 patients surgically treated for LGGs. The gross total resection (GTR) was performed in 35 patients (60.3%), subtotal resection (STR) was performed in 19 patients (31.7%) and partial resection (PR) or biopsy was performed in 9 patients (14.3%). We analyzed their progression-free survival (PFS), overall survival (OS), and malignant transformation with regard to age, gender, Karnofsky performance score (KPS), clinical presentation, tumor location, radiologic pattern, contrast enhancement, extent of removal, pathologic subtype, chemotherapy (CT) and radiotherapy (RT) treatment.

Results

Among all LGGs, the 3-year OS rate was 80% and the 5-year OS was 76%. The 3-year PFS rate was 83.6% and the 5-year PFS was 25%. The non-eloquent area location showed a longer PFS than the eloquent area location (p = 0.05). Oligodendroglial pathology showed a longer PFS compared to oligoastrocytomas and astrocytomas (p = 0.02). Patients older than 60 years had poorer OS than younger patients (p < 0.05). Female gender had a shorter OS than male gender (p < 0.05), and a KPS of 90 or 100 had a longer OS than a KPS of 80 (p < 0.05). Oligodendroglial pathology statistically correlated with a longer OS (p < 0.05).

Conclusion

The findings from our study, which were confirmed by uni- and multivariate analyses, demonstrated that radical tumor resection was associated with better long-term outcomes and tumor progression for patients with LGG.     

The assessment of prognostic factors in surgical treatment of low-grade gliomas: A prospective study

Objective

A prospective volumetric analysis of extent of resection (EOR) was carried out to assess surgical outcomes in adults diagnosed with hemispheric low grade gliomas (LGGs).

Materials and methods

68 consecutive patients diagnosed with LGGs were enrolled in the study. Pre- and post-operative tumor volumes and EOR were measured based on FLAIR MRI. Dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC MRI) was used for the assessment of relative cerebral blood volume (rCBV). Three outcome measures were assessed: overall survival (OS), progression-free survival (PFS), and malignant degeneration-free survival (MFS).

Results

In 6 (9%) patients permanent neurologic deficits were observed. No statistically significant dependence between the EOR and the occurrence of permanent deficits was found. The eloquent or close to the eloquent location was statistically connected with lower EOR (p = 0.023). The preoperative volume of tumors treated with gross total resection was significantly smaller than the volume of tumors in subtotal or partial resection groups (p = 0.020, p < 0.001, respectively). OS was predicted by age at diagnosis (p = 0.032), and rCBV (p = 0.002). Progression and malignant transformation occurred in 22 (32%) and 11 (16%) out of 68 patients. PFS was predicted by preoperative tumor volume (p = 0.005), postoperative tumor volume (p = 0.008), the EOR (p = 0.001), and by the rCBV (p = 0.033). MFS was predicted by preoperative tumor volume (p = 0.034), the EOR (p p = 0.020), and by rCBV (p = 0.022). Postoperative tumor volume was associated with a trend of improved MFS (p = 0.072). The univariate analysis shows the statistical trend for the relationship between histological subtype and PFS and MFS (p = 0.079, p = 0.078, respectively). Multivariate analysis selected preoperative tumor volume and rCBV as independently associated with PFS (p = 0.009, p = 0.019, respectively) and MFS (p = 0.023, p = 0.035, respectively). EOR was associated with a trend of improved PFS, and MFS (p = 0.069, p = 0.094, respectively).

Conclusions

Tumor resection of LGG with the use of intraoperative monitoring and neuronavigation is associated with a low risk of new permanent deficits, but EOR significantly decreases with the size of the tumor and/or its location in/close to the eloquent areas. Smaller preoperative tumor volume and greater EOR are significantly associated with longer OS, PFS and MFS. Preoperative rCBV is one of the important prognostic factors significantly connected with survival. Prognosis in LGGs is still under discussion. Other factors such as age, histopathological subtype and KPS should not be underestimated.     

Prognosis of pediatric high-grade gliomas with temozolomide treatment: a retrospective, multicenter study

Purpose

We analyzed the usefulness of initial or recurrent treatment of temozolomide (TMZ) in pediatric high-grade gliomas (HGGs).

Methods

Between 2002 and 2010, we performed surgery on 35 patients with 17 glioblastomas, 14 anaplastic astrocytomas, 3 anaplastic oligodendrogliomas, and 1 anaplastic oligoastrocytoma. The male-to-female ratio was 21:14, and the median age was 13?years (range, 3–18?years). The mean follow-up period was 15.9 (±1.8) months. As the TMZ treatment, 22 patients received the initial treatment and 13 patients at recurrence. We analyzed the prognostic significance of TMZ treatment, tumor location, extent of removal, pathology, and recurrence pattern.

Results

The median progression-free survival (PFS) and overall survival (OS) were 9.7 (±1.4) and 17.8 (±2.5) months, respectively. Based on univariate analysis, the median PFS was 9.9 (±1.6) months in the tumors located in the cerebral hemisphere and 5.6 (±1.3) months in the diencephalon (p?=?0.03). Median PFS was 12.5 (±1.7) months in the initial treatment and 6.8 (±0.8) months in the recurrent treatment (p?=?0.03). The median OS was 14.9 (±2.3) months in glioblastomas and 24.4 (±4.1) months in tumors with an anaplastic pathology (p?=?0.01). The median OS was 12.1 (±3.7) months in patients with cerebrospinal fluid (CSF) dissemination and 18.2 (±2.9) months in patients without CSF dissemination (p?=?0.02). Grades 3 and 4 treatment-related toxicity occurred in 7.7–9?% of the patients.

Conclusions

Initial or recurrent TMZ treatment in pediatric HGGs was safe and tolerable. Initial treatment showed improved PFS compared to recurrent treatment, and both showed similar OS.     

Brain stem tumors in children and adolescents: single institutional experience

Purpose

Pediatric brain stem tumors (BsT) are a heterogeneous group of diseases. Our aim was to analyze our experience to find out prognostic factors.

Method

A retrospective study with BsT patients was performed. Imaging characteristics, extension of surgery, pathology, and adjuvant therapy were analyzed and correlated with overall survival (OS) and progression-free survival (PFS) as outcome measures.

Result

Since 1980 to 2010, we analyzed 65 BsT patients, 41 of them girls (63 %), median age of 8 years (range 13.9?months to 17.6 years). Twenty-two patients (33.8 %) had diffuse intrinsic pontine gliomas (DIPG) and 43 (66.2 %) presented with focal BsT. Histology was available in 42 patients; the most frequent is low-grade glioma in 24/42 patients (57 %). DIPG’s histology (obtained usually at necropsy) confirmed five high-grade gliomas. After median follow-up of 49.3 months (0.5–175 months), 20/22 DIPG patients have died (90.9 %), while 27/43 with focal tumors were alive (62.8 %). Variables related to outcome were histology (better for low-grade glioma (LGG) OS p?<?0.001), surgery (better if operated OS p?<?0.001), and adjuvant therapy (worse if given, PFS p?=?0.001, OS p?=?0.024). The outcome for DIPG was dismal, median OS/EFS of 14.2/9.4 months, significantly worse than focal BsT (p?=?0.000), while OS/EFS was 122.8/87.2 months for focal intrinsic, 88.2/47.1 months for exophytic, and 124.4/54 months for cervico–medullary tumors: no differences were found among them, except the histology (OS p?<?0.001 for low-grade vs high-grade tumors).

Conclusion

BsT in children comprised two different groups: diffuse (DIPG) and focal gliomas. The DIPGs continue having a dismal prognosis, needing new approaches, while focal tumors including LGG have better prognosis.     

Neurosurgical tools to extend tumor resection in hemispheric low-grade gliomas: conventional and contrast enhanced ultrasonography

Purpose

Pediatric low-grade gliomas (LGGs) are the most frequent solid tumor in childhood. Based on an increasing number of literature reports, maximal safe resection is recommended as the first line of treatment whenever possible. However, distinguishing tumor tissue from the surrounding normal brain is often challenging with infiltrating neoplasms, even with the assistance of intraoperative, microscopic and conventional neuronavigation systems. Therefore, any technique that enhances the detection and visualization of LGGs intraoperatively is certainly desirable.

Methods

In this paper, we reviewed the role of intraoperative conventional ultrasound and contrast-enhanced ultrasound (CEUS) as a tool for extending tumor resection in LGGs. Moreover, our experience with this technology is reported and discussed.

Results

Both B-mode and CEUS are helpful in highlighting LGGs, detecting tumor margins and providing additional information such as vascularization, thus improving the safety of a more radical resection.

Conclusions

Although the full potentialities of the method are yet to be explored, intraoperative ultrasound is a promising tool in oncologic surgery and LGG surgery.

     

Temozolomide during and after Radiotherapy for Newly Diagnosed Glioblastomas : A Prospective Multicenter Study of Korean Patients

Objective

This study was performed to determine the safety and outcome of concurrent chemoradiotherapy (CCRT) and adjuvant chemotherapy with temozolomide for Korean patients with a newly diagnosed glioblastoma.

Methods

Patients were recruited from four institutions between 2004 and 2007. The patients received fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks and daily temozolomide, followed by 6 cycles of adjuvant temozolomide. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS), response, and safety.

Results

A total of 103 patients were enrolled in this study. Ninety-six patients (93%) completed the CCRT and 54 patients (52%) received 6 cycles of adjuvant temozolomide. The response rate was 73% (53/73) and the tumor control rate was 92% (67/73). Of the 96 patients who completed the CCRT, the median OS was 18.0 months and the 1- and 2-year OS rates were 74 and 38%, respectively. The median PFS was 10.0 months and the 1- and 2-year PFS rates were 33 and 16%, respectively. The only significant prognostic factor of survival was the extent of surgical resection (p<0.05). CCRT resulted in grade 3 or 4 hematologic toxic effects in 8% of patients. No opportunistic infections were noted.

Conclusion

This study is the first prospective multi-institutional report of CCRT and adjuvant chemotherapy with temozolomide for patients with a newly diagnosed glioblastoma in Korea. The current protocol may prolong the survival of Korean patients with a glioblastoma and may be tolerable in terms of toxicity.     

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 %.

     

Temozolomide Salvage Chemotherapy for Recurrent Anaplastic Oligodendroglioma and Oligo-Astrocytoma

Objective

To evaluate the efficacy of temozolomide (TMZ) chemotherapy for recurrent anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA).

Methods

A multi-center retrospective trial enrolled seventy-two patients with histologically proven AO/AOA who underwent TMZ chemotherapy for their recurrent tumors from 2006 to 2010. TMZ was administered orally (150 to 200 mg/m²/day) for 5 days per 28 days until unacceptable toxicity occurred or tumor progression was observed.

Results

TMZ chemotherapy cycles administered was median 5.3 (range, 1-41). The objective response rate was 24% including 8 cases (11%) of complete response and another 23 patients (32%) were remained as stable disease. Severe side effects (≥grade 3) occurred only in 9 patients (13%). Progression-free survival (PFS) of all patients was a median 8.0 months (95% confidence interval, 6.0-10.0). The time to recurrence of a year or after was a favorable prognostic factor for PFS (p<0.05). Overall survival (OS) was apparently differed by the patient''s histology, as AOA patients survived a median OS of 18.0 months while AO patients did not reach median OS at median follow-up of 11.5 months (range 2.7-65 months). Good performance status of Eastern Cooperative Oncology Group 0 and 1 showed prolonged OS (p<0.01).

Conclusion

For recurrent AO/AOA after surgery followed by radiation therapy, TMZ could be recommended as a salvage therapy at the estimated efficacy equal to procarbazine, lomustine, and vincristine (PCV) chemotherapy at first relapse. For patients previously treated with PCV, TMZ is a favorable therapeutic option as 2nd line salvage chemotherapy with an acceptable toxicity rate.     

Outcome in unresectable glioblastoma: <Emphasis Type="Italic">MGMT</Emphasis> promoter methylation makes the difference

In 2011, we reported a predominant prognostic/predictive role of MGMT promoter methylation status on progression-free survival (PFS) in unresectable glioblastoma patients undergoing upfront radiotherapy plus concomitant and maintenance temozolomide (RTX/TMZ → TMZ). We, here, present the final results of this prospective study focussing on the prognostic/predictive value of MGMT promoter methylation status for death risk stratification. Overall, 56 adult patients with unresectable, biopsy proven glioblastoma were prospectively assigned to upfront RTX/TMZ → TMZ treatment between March 2006 and August 2008. Last follow-up was performed in June 2016. MGMT promoter methylation was determined using methylation-specific PCR (MSP) and sodium bisulfite sequencing. Analyses were done by intention to treat. Prognostic factors were obtained from proportional hazard models. At the time of the final analysis 55 patients showed progressive disease and 53 patients had died. MGMT promoter was methylated (unmethylated) in 30 (26) patients. Methylation of the MGMT promoter was the strongest favorable predictor for overall survival (OS, median: 20.3 vs. 7.3 months, p < 0.001, HR 0.30, 95% CI 0.16–0.55), and PFS (median: 15.0 vs. 6.1 months, p < 0.001, HR 0.31, 95% CI 0.17–0.57) and was also associated with higher frequencies of treatment response and prolonged post-recurrence survival (PRS, median: 4.5 vs. 1.4 months, p < 0.002, HR 0.39, 95% CI 0.21–0.71). Knowledge of MGMT promoter methylation status is essential for patients’ counseling, prognostic evaluation, and for the design of future trials dealing with unresectable glioblastomas.     

Electrical impedance myography for monitoring motor neuron loss in the SOD1 G93A amyotrophic lateral sclerosis rat

Objective

Human studies have shown that electrical impedance myography (EIM), a technique based on the surface application of high-frequency, low-intensity electrical current to localized areas of muscle, is sensitive to muscle denervation. In this study, we examined the role of EIM as a potential biomarker for assessing ALS disease progression in the SOD1 transgenic rat by comparing it to motor unit number estimation (MUNE).

Methods

Multi-frequency EIM and MUNE were performed twice weekly in 16 rats from approximately 10 weeks of age onward. Four different EIM measures were evaluated, including the previously studied 50 kHz phase and three condensed multi-frequency parameters.

Results

The rate of deterioration in the multi-frequency phase data from 100–500 kHz had the strongest correlation to survival (ρ = 0.79, p < 0.001), surpassing that of MUNE (ρ = 0.57, p = 0.020). These two measures were also strongly correlated (ρ = −0.94, p < 0.001) to one another.

Conclusions

These findings support that EIM is an effective tool for assessing disease progression in the ALS rat.

Significance

Given its ease of application and ability to assess virtually any superficial muscle, EIM deserves further study as a biomarker in human ALS clinical therapeutic trials.     

High-grade glioma in children and adolescents: a single-center experience

Purpose

The aim of this study was to report the outcome in children with high-grade astrocytoma outside the brain stem and spinal cord that were treated at a single center.

Materials and methods

The study included 26 patients with anaplastic astrocytoma and 37 patients with glioblastoma; all patients were aged ≤18 years. At initial diagnosis, 18 of the patients with glioblastoma received only temozolomide (TMZ), 14 received other chemotherapies, and 5 did not receive any chemotherapy. Among the patients with anaplastic astrocytoma, 9 received TMZ, 9 received other chemotherapy regimens, and 8 patients did not receive any chemotherapy. The median radiotherapy dose in all patients was 60 Gy.

Results

Median age of the patients was 12.5 years. Median overall survival was 20 months and mean progression-free survival was 4.7–11.3 months (median: 8 months) in all patients. Patients with a Karnofsky performance score (KPS) ≥70 had median overall survival of 32 months, versus 7 months in those with a KPS < 70. Patients aged <15 years had median survival of 38 months, versus 16 months in those aged 15–18 years. Patients with anaplastic astrocytoma that received TMZ, other chemotherapy regimens, and no chemotherapy had median survival of 21 months, 132 months, and 11 months, respectively. Patients with glioblastoma that received TMZ, other chemotherapy regimens, and no chemotherapy had median survival of 32 months, 12 months, and 8 months, respectively.

Conclusion

In the present study, patients with anaplastic astrocytoma treated with chemotherapy protocols other than TMZ had the longest OS; however, in the glioblastoma group, OS was 32 months in those treated with standard TMZ and 12 months in those treated with other protocols (P = 0.493). Although TMZ is less toxic than PCV, it was not shown to be superior.

     

Clinical considerations and surgical approaches for low-grade gliomas in deep hemispheric locations: thalamic lesions

Background

Tumors with epicenter in the thalamus occur in about 4 % of pediatric brain tumors. The histological diagnosis is mainly gliomas. Among them, low-grade glioma (LGG) constituted of a significant entity of the tumors (Cuccia et al., Childs Nerv Syst 13:514–521, 1997; Puget et al., J Neurosurg 106:354–362, 2007; Bernstein et al., J Neurosurg 61:649–656, 1984; Bilginer et al., Childs Nerv Syst 30:1493–1498, 2014). Since Kelly’s report in 1989, >90 % resection of thalamic tumors were achieved in reported series (Ozek and Ture, Childs Nerv Syst 18:450–6, 2002; Villarejo et al., Childs Nerv Syst 10:111–114, 1994; Moshel et al., Neurosurgery 61:66–75, 2007; Albright, J Neurosurg 100(5 Suppl Pediatrics): 468–472, 2004; Kelly, Neurosurgery 25:185–195, 1989; Drake et al., Neurosurgery 29: 27–33, 1991).

Materials and methods

Sixty-nine cases of thalamic tumors in children were retrospectively reviewed. There were 25 cases of LGGs. We analyzed our experience and correlated it with reported series.

Results

Summing up of 4 reported series and the present series, there were 267 cases of thalamic tumors in children. Among these tumors, 107 (40.1 %) were LGGs and 91 (34.1 %) were low-grade astrocytomas (LGAs). In the present series, all of the 25 LGGs were LGAs that consisted of 11 pilocytic astrocytomas (PAs) and 14 diffuse astrocytomas (DAs). Six cases received biopsy sampling only. The remaining 19 cases received different degrees of surgical resection via several approaches. Radical (>90 %) resection was achieved better in PAs comparing with DAs. There was no operative mortality. Two patients had increased neurological deficits. In a mean follow-up period of 11.9 years, three patients died of tumor progression and one patient died of anaplastic change. The 5- and 10-year overall survival (OS) was 87.1 and 87.1 %, respectively.

Conclusion

Thalamic LGGs are mainly LGAs and are indolent. The rate of >90 % resection was relatively low in the present series. By applying contemporary diagnostic MRI studies, surgical facilities, and appropriate approaches in selective cases, we may try maximum neuroprotective radical (>90 %) resection.

     

Diffuse intrinsic pontine glioma in children and adolescents: a single-center experience

Background

Patients with diffuse intrinsic pontine glioma (DIPG) have a very poor prognosis. Only radiotherapy (XRT) has proven to be effective in delaying the disease progression. Several chemotherapy schedules have been applied so far, but none demonstrated significant improvements in progression and survival.

Methods

We retrospectively analyzed the clinical data of children diagnosed with DIPG at our center (Pediatric Hospital “Regina Margherita,” Turin, Italy) between 1999 and 2013. Progression-free survival (PFS) and overall survival (OS) were used to describe the outcomes.

Results

Twenty-four children were included in our report. Patients diagnosed before March 2003 (n?=?12) were treated with XRT and vincristine (VCR); the remaining 12 patients received XRT and temozolomide (TMZ). Progression-free survival was 18.8 % at 1 year (SE?=?7.6 %), while overall survival was 44.1 % at 1 year (SE?=?9.9 %). Median PFS was 8.1 months, whereas median OS was 11.2 months. No statistically significant difference in PFS or OS was evidenced between the two treatment groups.

Conclusion

Radiotherapy followed by VCR or TMZ allows obtaining results that are in line with previous reports, with no advantages over other similar treatment schedules. DIPGs are challenging tumors with a dismal outcome. Further research and newer therapies are urgently needed in order to achieve improvements in survival.