Re-evaluating surgery and re-irradiation for locally recurrent pediatric ependymoma – a multi-institutional study

Background The goal of this study was to evaluate extent of surgical resection, and timing and volume of re-irradiation, on survival for children with locally recurrent ependymoma. Methods Children with locally recurrent ependymoma treated with a second course of fractionated radiotherapy (RT2) from six North American cancer centres were reviewed. The index time was from the start of RT2 unless otherwise stated. Results 35 patients were included in the study. The median doses for first radiation (RT1) and RT2 were 55.8 and 54 Gy, respectively. Median follow-up time was 5.6 years. Median overall survival (OS) for all patients from RT2 was 65 months. Gross total resection (GTR) was performed in 46% and 66% of patients prior to RT1 and RT2, respectively. GTR prior to RT2 was independently associated with improved progression free survival (PFS) for all patients (HR 0.41, p = 0.04), with an OS benefit (HR 0.26, p = 0.03) for infratentorial tumours. Median PFS was superior with craniospinal irradiation (CSI) RT2 (not reached) compared to focal RT2 (56.9 months; log-rank p = 0.03). All distant failures (except one) occurred after focal RT2. Local failures after focal RT2 were predominantly in patients with less than GTR pre-RT2. Conclusions Patients with locally recurrent pediatric ependymoma should be considered for re-treatment with repeat maximal safe resection (ideally GTR) and CSI re-irradiation, with careful discussion of the potential side effects of these treatments.

QOLP-08. THE LANDSCAPE OF EPILEPSY ASSOCIATED WITH DIFFUSELY INFILTRATIVE GLIOMAS

Seizures are among the most prevalent co-morbidities associated with glioma, and pose a serious threat to patients. Our prior work showed that IDH mutation (IDHmut) was associated with much greater seizure frequency at the time of initial glioma diagnosis. However, less is known about the variables that contribute to seizure risk throughout the course of disease. We therefore collected data from 247 patients with grade 2–4 glioma, and determined seizure risk using Kaplan-Meier survival probabilities and multivariable cox regression analyses. Median follow-up of IDH wildtype (IDHwt) and IDHmut glioma patients was 15 months and 36 months, respectively. Incidence of pre-operative seizures for IDHwt and IDHmut patients was 75/168 (45%) and 60/79 (76%), and incidence of post-operative seizures was 70/168 (42%) and 43/79 (54%), respectively. Patients who had a pre-operative seizure had a shorter time to their first post-operative seizure than patients who never had a pre-operative seizure in both IDHwt (P< 0.0001) and IDHmut (P= 0.039) cohorts. Among IDHmut glioma patients, those with subtotal resections developed post-operative seizures faster (median time to first seizure= 9.9 months) than those with gross-total resections (median not reached) (P= 0.0005), but a similar pattern was not observed in IDHwt glioma patients (P= 0.20). Those with IDHmut astrocytomas more quickly developed post-operative seizures (median= 11.1 months), compared to those with IDHwt astrocytomas (24.9 months) or IDHmut oligodendrogliomas (median not reached) (P= 0.033). Tumor progression closely followed post-operative seizures in patients with IDHwt gliomas when either their first post-operative seizure occurred longer than 6 months following resection, or when their post-operative seizures worsened in quality. These data suggest the best predictors of post-operative seizures are as follows: the presence of pre-operative seizures; extent of surgical resection; IDHmut status. These data will help clinicians better manage glioma patients by identifying those at greatest risk of seizures.

Fluorescence-Guided Surgery in the Surgical Treatment of Gliomas: Past, Present and Future

Gliomas are central nervous systems tumours which are diffusely infiltrative and difficult to treat. The extent of surgical resection is correlated with improved outcomes, including survival and disease-free progression. Cancerous tissue can be directly visualised intra-operatively under fluorescence by administration of 5-aminolevulinic acid to the patient. The adoption of this technique has allowed surgeons worldwide to achieve greater extents of resection, with implications for improved prognosis. However, there are practical limitations to use of 5-aminolevulinic acid. New adjuncts in the field of fluorescence-guided surgery aim to improve recognition of the interface between tumour and brain with the objective of improving resection and patient outcomes.

Different prognostic effect of surgery, radiation and chemotherapy in pediatric medulloblastoma less and over three years old: A Surveillance, Epidemiology, and End Results (SEER) analysis

Introduction To clarify the prognostic value of extent of surgical resection, radiation and chemotherapy in pediatric medulloblastoma patients < 3 years old and ≥ 3 years old. Methods We used the Surveillance, Epidemiology, and End Results program to identify 1,495 pediatric patients diagnosed between 1973 and 2016 with medulloblastoma. Patients with incomplete or unknown clinical information were excluded. Basic characteristics between patients < 3 years old and ≥ 3 years old were compared. Then, we used Cox regression to investigate the impact of extent of surgical resection, radiation and chemotherapy on patient outcome. Results Gross total resection only significantly improved patient outcome in those ≥ 3 years old, and radiation independently correlated to better OS and PFS in patients ≥ 3 years old (all p < 0.05). However, chemotherapy only benefited patient outcome in those < 3 years old (all p < 0.05). Furthermore, in those ≥ 3 years old patients underwent surgical procedures, radiation alone confer survival benefit only in those received gross total resection (p < 0.05) but not in partial resection or biopsy (p > 0.05). Notably, adjuvant radiation plus chemotherapy largely improved patient survival independent of extent of resection (p < 0.05). Conclusions The extent of resection should be differentially considered and applied between pediatric medulloblastoma patients < 3 years old and ≥ 3 years old, so are the adjuvant radio- and chemo- therapies.

Role of 11C Methionine Positron Emission Tomography (11CMETPET) for Surgery and Radiation Therapy Planning in Newly Diagnosed Glioblastoma Patients Enrolled into a Phase II Clinical Study

(1) Background: We investigated the role of [11C]-methionine PET in a cohort of newly diagnosed glioblastoma multiforme (GBM) patients to evaluate whether it could modify the extent of surgical resection and improve radiation therapy volume delineation. (2) Methods: Newly diagnosed GBM patients, ages 18–70, with a Karnofsky performance scale (KPS) ≥ 70 with available MRI and [11C]-methionine PET were included. Patients were treated with different amounts of surgical resection followed by radio-chemotherapy. The role of [11C]-methionine PET in surgical and RT planning was analyzed. A threshold of SUVmax was searched. (3) Results: From August 2013 to April 2016, 93 patients were treated and included in this analysis. Residual tumor volume was detected in 63 cases on MRI and in 78 on [11C]-methionine PET, including 15 receiving gross total resection. The location of uptake was mainly observed in FLAIR abnormalities. [11C]-methionine uptake changed RT volume in 11% of patients. The presence of [11C]-methionine uptake in patients receiving GTR proved to influence survival (p = 0.029). The threshold of the SUVmax conditioning outcome was five. (4) Conclusions: [11C]-methionine PET allowed to detect areas at higher risk of recurrence located in FLAIR abnormalities in patients affected by GBM. A challenging issue is represented by integrating morphological and functional imaging to better define the extent of surgical resection to perform.

Recurrent Myxoid Chondrosarcoma of Mandible: A Case Report

Myxoid chondrosarcoma is a rare malignant neoplasm of bone or soft tissue origin, characterised by the presence of chondroid and myxoid matrix. These are traditionally radio resistant tumours, so wide surgical resection remains the mainstay of treatment. However, radiotherapy is generally advised for high-grade lesions with poor prognostic factors with adjuvant chemotherapy. The treatment decisions are primarily guided by the histological grade, extent of surgical resection, and site of the neoplasm. A case of a 28-year-old male who presented with recurrent painful swelling in the mandibular region is discussed here. To date, very few cases of Extraskeletal Myxoid Chondrosarcoma (EMC) occurring in the mandible region have been reported. So, due to the paucity of available literature, controversies still exist regarding effective treatment approaches in newly diagnosed and recurrent cases. This case reports the clinical presentation, histopathology, radiological characteristics, immune profile, and treatment modalities used in EMC with a comprehensive and relevant review of the literature.

The influence of subventricular zone involvement in extent of resection and tumor growth pattern of glioblastoma

ObjectivesIsocitrate dehydrogenase (IDH1/2) mutations and O6-alkylguanine DNA methyltransferase (MGMT) promoter methylations are acknowledged survival predictors in patients with glioblastoma (GB). Moreover, tumor growth patterns like multifocality and subventricular zone (SVZ) involvement seem to be associated with poorer outcomes. Here, we wanted to evaluate the influence of the SVZ involvement and the multifocal tumor growth on the extent of surgical resection and its correlation with overall survival (OS) and molecular characteristics of patients with GB.MethodsAdult patients with primary GB who underwent surgery at our department between 2012 and 2014 were included. Preoperative magnetic resonance imaging findings were analyzed with regard to tumor location, presence of multifocality and SVZ involvement. The extent of surgical resection as well as clinical and molecular parameters was collected from electronic patient records. Univariate and multivariate analyses were performed.ResultsTwo hundred eight patients were retrospectively analyzed, comprising 90 (43.3%) female individuals with a mean age of 62.9 (±12.26) years and OS of 10.2 months (±8.9). Unifocal tumor location was a predictor for better OS with a mean of 11.4 (±9.4) months (vs. 8.0 [±7.4] months, p=0.008). Affection of the SVZ was also associated with lower surgical resection rates (p<0.001). SVZ involvement revealed with 7.8 (±7.0) months a significant worse OS [vs. 13.9 (±10.1) months, p<0.001]. All six IDH1/2 wildtype tumors showed an unifocal location (p=0.066). MGMT promoter methylation was not associated with multifocal tumor growth (p=0.649) or SVZ involvement (p=0.348). Multivariate analysis confirmed independent association between the SVZ involvement and OS (p=0.001).ConclusionThe involvement of the SVZ appears to have an influence on a lower resection rate of GB. This negative impact of SVZ on GB outcome might be related to lesser extent of resection, higher rates of multifocality and greater surgical morbidity but not inevitably to IDH1/2 mutation and MGMT promoter methylation status.

Is There A Role for Limited Parotid Resections for Primary Malignant Parotid Tumors?

(1) Background: Lateral or total parotidectomy are the standard surgical treatments for malignant parotid tumors. However, some authors have proposed a more limited procedure. (2) Methods: We performed a review of the literature on this topic. Studies were included that met the following criteria: malignant parotid tumors, information about the extent of surgical resection, treated with less than a complete lateral lobectomy, and information on local control and/or survival. Nine articles fulfilled the inclusion criteria. (3) Results: Eight of the nine series reported favorable results for the more limited approaches. Most used them for small, mobile, low-grade cancers in the lateral parotid lobe. Most authors have used a limited partial lateral lobectomy for a presumed benign lesion. The remaining study analyzed pediatric patients treated with enucleation with poor local control. (4) Conclusions: There is weak evidence for recommending less extensive procedures than a lateral parotid lobectomy. In the unique case of a partial lateral parotidectomy performed for a tumor initially thought to be benign but pathologically proved to be malignant, close follow-up can be recommended for low grade T1 that has been excised with free margins and does not have adverse prognostic factors.