An effective strategy for salvage therapy in refractory or relapsed childhood brain tumours is yet to be established. A national retrospective review of 135 children diagnosed with treatment refractory or recurrent MB from 2000 to 2021 at 5 academic Canadian pediatric neurosurgical centers was performed. The mean age at diagnosis was 7.09 years (SD 4.37) with a male predominance (64.4

Abstract Background Medulloblastoma (MB) is the most common malignant pediatric brain tumor. MB is subdivided into four main subgroups: SHH, WNT, Group 3 (G3-MB) and Group 4 (G4-MB). Despite advancements in treatment regimens, 30% of MB patients succumb to metastasis and treatment relapse. G4-MB represents a large subset of patients ranging from high risk to good prognosis. G4-MB tumor biology remains poorly understood and molecularly ambiguous. Pre-clinical development is obstructed by suboptimal existing models. here, we report the development of novel G4-MB models with the capacity for in vitro propagation and preclinical drug screening. Methods Two G4-MB tumor lines (MBT375 and MBT417) were derived from patient tumors and characterized by NanoString, RNA-seq and DNA methylation profiling. Subsequently, these models were serially engrafted in mice or cultured in vitro. G4-MB models were assessed for stem cell marker BMI1 expression levels and subsequent dose-response and synergy assays were performed in comparison to neural stem cells with BMI1 targeted drugs. G4-MB cells were transduced with firefly luciferase for optimized in vivo modelling. Results We present two novel G4-MB patient-derived orthotopic mouse models: MBT375 (subtype VIII) and MBT417 (subtype VI), with the capacity for short-term in vitro propagation, genetic manipulation, and improved tumorigenicity. Importantly, MBT375-engrafted mice reliably develop spinal metastatic disease. We demonstrate in vitro that repurposing G3-MB specific BMI1-targeted therapeutic strategies is a rational approach for the most common and often difficult-to-treat MB subtype. Conclusions We developed novel G4-MB models serving as in vitro discovery platforms to identify novel cancer-selective treatment modalities.

BACKGROUND:Pediatric intraspinal epidermoid cysts are rare with potential to cause life-altering outcomes if not addressed. Reports to date describe symptomatic presentations including loss of bladder or bowel function and motor and sensory losses. This case report identifies the diagnostic challenge of an asymptomatic intraspinal epidermoid cyst in the cauda equina region presenting in a 7-year-old male with juvenile idiopathic arthritis (JIA). DIAGNOSIS:An advanced physiotherapist practitioner assessed and diagnosed a previously healthy 7-year-old-male of South Asian descent with JIA based on persistent knee joint effusions. Complicating factors delayed the investigation of abnormal functional movement patterns, spinal and hip rigidity and severe restriction of straight leg raise, all atypical for JIA. Further delaying the diagnosis was the lack of subjective complaints including no pain, no reported functional deficits, and no neurologic symptoms. A spinal MRI investigation 10-months from initial appointment identified intraspinal epidermoid cysts occupying the cauda equina region requiring urgent referral to neurosurgery. DISCUSSION:Clinical characteristics and pattern recognition are essential for diagnosing spinal conditions in pediatric populations. Diagnostic challenges present in this case included co-morbidity (JIA), a severe adverse reaction to treatment, a lack of subjective complaints and a very low prevalence of intraspinal epidermoid cysts. IMPACT STATEMENTS:Early signs of pediatric asymptomatic intraspinal epidermoid cysts included abnormal functional movement patterns, rigidity of spine, severely limited straight leg raise and hip flexion without pain. Advanced physiotherapist practitioners can be integral to pediatric rheumatology teams considering their basic knowledge in musculoskeletal examination and functional mobility assessment when identifying rare spinal conditions that present within the complex context of rheumatic diseases.

Cerebellar mutism (CM) is characterized by a significant loss of speech in children following posterior fossa (PF) surgery. The biological origin of CM remains unclear and is the subject of ongoing debate. Significant recovery from CM is less likely than previously described despite rigorous multidisciplinary neuro-rehabilitational efforts. A national multi-centered retrospective review of all children undergoing PF resection in four midsized Canadian academic pediatric institutions was undertaken. Patient, tumor and surgical factors associated with the post-operative development of CM were reviewed. Retrospective identification of PF surgery patients including those developing and those that did not (internal control). The study identified 258 patients across the 4 centers between 2010 and 2020 (mean age 6.73 years; 42.2

Background: The competency-based medical education (CBME) model has been recently implemented in spinal neurosurgical and orthopedic residencies. This model is grounded on entrustable professional activities (EPAs) that allow the assessment of clinical milestones. Integrating quantitative metrics to evaluate procedural competencies could refine the assessment’s scope. This survey, administered to program directors (PDs), aims to evaluate the current state and anticipated needs for quantitative evaluation to develop innovative assessment techniques. Methods: We surveyed 32 PDs of neurosurgical (N=14) and orthopedics (N=16) programs with a spine service via RedCap. We collected information on the programs’ characteristics. We inquired about existing assessment methods and the perceived values of developing quantitative metrics to assess spinal technical competencies using thirteen questions. Results: The response rate was 53%. All programs use EPAs to assess procedural competencies through direct observation in the operation room. One surgical program employed quantitative metrics for examination. Four PD valued the profitability of quantitative evaluation methods in a clinical or simulatory context. Conclusions: The use of quantitative metrics to assess spinal surgical competencies in Canadian neurosurgical and orthopedic residency programs is seldom. Despite its underutilization, PDs acknowledge the potential for quantitation to improve the accuracy and reliability of CBME assessments in both simulated and clinical settings.

Purpose To determine whether intraoperative adjunctive EVD placement in patients with a posterior fossa tumor (PFT) led to improved surgical, radiographic, and clinical outcomes compared to those who did not receive an EVD.Methods Patients were grouped as those who underwent routine intraoperative adjunctive EVD insertion and those who did not at time of PFT resection. Patients who pre-operatively required a clinically indicated EVD insertion were excluded. Comparative analyses between both groups were conducted to evaluate clinical, radiological, and pathological outcomes. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were computed for post-operative outcomes.Results Fifty-five selected patients were included, 15 who had an EVD placed at the time of PFT resection surgery, and 40 who did not. Children without an EVD did not experience a higher rate of complications or poorer post-operative outcomes compared to those with an EVD placed during resection surgery. There was no significant difference in the degree of gross total resection (p = 0.129), post-operative CSF leak (p = 1.000), and post-operative hemorrhage (p = 0.554) between those with an EVD and those without. The frequency of new cranial nerve deficits post-operatively was higher in those with an EVD (40%) compared to those without (3%, p = 0.001). There was a trend towards more frequently observed post-operative hydrocephalus in the EVD group (p = 0.057).Conclusion The routine use of EVD as an intraoperative adjunct in clinically stable pediatric patients with posterior fossa tumors and hydrocephalus may not be associated with improved radiological or clinical outcomes.

BACKGROUND Juvenile pilocytic astrocytoma (JPA) typically follows an indolent clinical course. The first-line treatment for most JPAs is surgical resection. However, a gross total resection may not be feasible for deep-seated lesions and/or infiltrative tumors, leading to multimodal treatment approaches that may be complicated by patient age and tumor location. Despite the prevalence of pediatric JPAs, there is no single approach to treating progressive disease. METHODS We investigated the multifaceted management of progressive JPAs through a retrospective analysis of JPAs treated at a single center over an 18-year period (1998-2016). All cases were categorized according to location, whether supratentorial or infratentorial, and for each case we calculated the number of interventions and the time between interventions. RESULTS We identified a total of 40 JPAs, (11 supratentorial, 29 infratentorial). Total number of interventions among all supratentorial JPA patients was 21 (average 2 interventions/patient). The total number of interventions among infratentorial JPAs was 40 (average 1.4 interventions/patient). CONCLUSIONS Treatment of progressive JPA is variable and may require numerous surgeries and adjuvant therapies.

Medulloblastoma (MB) is defined by four molecular subgroups (Wnt, Shh, Group 3, Group 4) with Wnt MB having the most favorable prognosis. Since prior reports have illustrated the antitumorigenic role of Wnt activation in Shh MB, we aimed to assess the effects of activated canonical Wnt signaling in Group 3 and 4 MBs. By using primary patient-derived MB brain tumor-initiating cell (BTIC) lines, we characterize differences in the tumor-initiating capacity of Wnt, Group 3, and Group 4 MB. With single cell RNA-seq technology, we demonstrate the presence of rare Wnt-active cells in non-Wnt MBs, which functionally retain the impaired tumorigenic potential of Wnt MB. In treating MB xenografts with a Wnt agonist, we provide a rational therapeutic option in which the protective effects of Wnt-driven MBs may be augmented in Group 3 and 4 MB and thereby support emerging data for a context-dependent tumor suppressive role for Wnt/β-catenin signaling.

Purpose: The present study aims to determine the tumor-related, clinical, and demographic factors associated with extent of resection (EOR) and post-operative outcomes in JPA patients. Methods: All patients with JPA, identified from a single-center brain tumour data base, were included in this retrospective analysis. Pre-operative MRI scans were reviewed by a single neurosurgeon blinded to the EOR. JPA cases that exhibited no residual tumor post-operatively were assigned to the GTR group, all other tumors were assigned to the <GTR group. Tumor-related, clinical and demographic variables as well as perioperative morbidities were compared between both groups. Results: Of the 28 patients included, 15 had a GTR (46% male; median age: 7.5 years; range: 1.16-14.9) and 13 had <GTR (69.2% male; median age: 10.6 years: range: 0.66-17.68). Tumor location reached statistical significance, as there were significantly more cerebellar tumors in the GTR group (86.7%) compared to the <GTR group (38.5%) (p = 0.016). GTR cases had a significantly longer average follow-up interval (6.6 months) than <GTR cases (4.5 months) (p = 0.031). All demographic variables, clinical variables and tumor-related factors showed no significant differences between the two groups. There were no differences between GTR and <GTR cases in terms of perioperative outcomes. Conclusions: This study shows other than location of the lesion in the cerebellum, demographic, clinical and tumor-related variables are not associated with EOR in children with JPA. GTR was associated with an extended follow-up interval but not with increased perioperative morbidities compared to those with <GTR. (C) 2019 Elsevier Ltd. All rights reserved.

Background Postoperative length of stay (LOS) carries a high burden of healthcare costs. In resource-intense specialties such as neurosurgery, it is imperative to identify factors that influence LOS to improve care. The current study investigates the potential for variables that affect clinical presentation, tumor characteristics, treatment modalities, and postoperative complications to impact overall LOS in pediatric brain tumor patients. Methods A retrospective cohort study design was used with patients enrolled in the McMaster Pediatric Brain Tumor Study Group database. All patients up to 18 years of age, presenting with a newly diagnosed brain tumor admitted to and discharged from neurosurgery, were included. Patients were sorted into three cohorts: short LOS (<= 3 days), extended LOS (>= 20 days), and control LOS (4-19 days). Results Of the 124 patients included, 20 (65% male; median age: 9.1 years; range, 0.8-17.4 years) were considered short LOS, 28 (61% male; median age: 4.7 years; range, 0.4-14.7 years) were considered extended LOS, and 76 (57% male; median age: 8.5 years; range, 0.3-17.9 years) were considered control LOS. Variables that prolonged LOS were emesis at presentation (P < 0.001), developmental delay (P = 0.02), multiple surgeries (P = 0.004), tumor location (P < 0.05), subtotal resection (P = 0.02), feeding tube (P < 0.001), adjuvant chemoradiotherapy (P < 0.001), and posterior fossa syndrome (P = 0.004). Conclusions This study identifies variables related to clinical presentation, tumor characteristics, treatment modalities, and postoperative complications associated with extended LOS. These findings uncover novel predictors of LOS that can be used to guide future research and improve health resource management.

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INTRODUCTION:Children diagnosed with medulloblastoma (MB) who are refractory to upfront therapy or experience recurrence have very poor prognoses. Although phase I and phase II trials exist, these treatments bear significant treatment-related morbidity and mortality.METHODS:A retrospective review of children diagnosed with a recurrence of MB from 2002 to 2015 at McMaster University was undertaken.RESULTS:Recurrent disease in 10 patients involved leptomeningeal dissemination, with 3 experiencing local recurrence. In three recurrent patients the disease significantly progressed, and the children were palliated. The remaining 10 children underwent some form of salvage therapy, including surgical re-resection, radiation, and chemotherapy, either in isolation or in varying combinations. Of the 13 children experiencing treatment-refractory or recurrent disease, 4 are currently alive with a median follow-up of 38.5 months (75.5 months). Of the eight patients with molecular subgrouping data, none of the Wnt MB experienced recurrence.CONCLUSION:Recurrent MB carried a poor prognosis with a 5-year overall survival (OS) of 18.2% despite the administration of salvage therapy. The upfront therapy received, available treatment, and tolerability of the proposed salvage therapy resulted in significant heterogeneity in the treatment of our recurrent cohort.

Background: Children diagnosed with medulloblastoma (MB) that are refractory to upfront therapy or experience recurrence have very poor prognoses. Reports of phase I and II studies for these children exist, but bear significant treatment related morbidity and mortality. Methods: A retrospective review of children diagnosed with a pediatric MB from 2002-2015 from the McMaster Pediatric Brain Tumour Study Group (PBTSG) captured a number of pediatric recurrent MB. Results: Over the 13-year period, 31 children with a histological diagnosis of MB were treated. At two years, 21 (67.7%) of 31 patients were free of recurrence and 25 (80.6%) survived. Thirteen children had recurrent or treatment refractory MB. mean time to recurrence was 14.6 months. The mean follow-up for survivors of recurrent MB was 4.0 years. In 3 recurrent MB, the disease had significantly progressed and the patients palliated. For the remaining children, therapy offered included surgery, radiation, and chemotherapy agents either in isolation or in varying combinations. Conclusions: Recurrent MB in our cohort carried a poor prognosis despite administration of salvage therapy. Though there is standardization of the upfront treatment exists, we observed great heterogeneity in the treatment of our 13 patients experiencing recurrence. A greater understanding of the biology of recurrent MB has the potential to guide salvage therapy.

Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor, representing 20% of newly diagnosed childhood central nervous system malignancies. Although advances in multimodal therapy yielded a 5-year survivorship of 80%, MB still accounts for the leading cause of childhood cancer mortality. In this work, we describe the epigenetic regulator BMI1 as a novel therapeutic target for the treatment of recurrent human Group 3 MB, a childhood brain tumor for which there is virtually no treatment option beyond palliation. Current clinical trials for recurrent MB patients based on genomic profiles of primary, treatment-naive tumors will provide limited clinical benefit since recurrent metastatic MBs are highly genetically divergent from their primary tumor. Using a small molecule inhibitor against BMI1, PTC-028, we were able to demonstrate complete ablation of self-renewal of MB stem cells in vitro. When administered to mice xenografted with patient tumors, we observed significant reduction in tumor burden in both local and metastatic compartments and subsequent increased survival, without neurotoxicity. Strikingly, serial in vivo re-transplantation assays demonstrated a marked reduction in tumor initiation ability of recurrent MB cells upon re-transplantation of PTC-028-treated cells into secondary recipient mouse brains. As Group 3 MB is often metastatic and uniformly fatal at recurrence, with no current or planned trials of targeted therapy, an efficacious targeted agent would be rapidly transitioned to clinical trials.

Abstract Brain tumors represent the leading cause of childhood cancer mortality, of which medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Current molecular subgroups of MB recognize distinct disease entities of which activated Wnt signaling (monosomy 6, exon 3 mutations in CTNNB1, and Wnt gene signature) is associated with a distinct subgroup and the best overall outcome. In contrast, only non-Wnt MBs are characterized by metastatic disease, increased rate of recurrence, and poor overall survivorship. Given the excellent clinical outcome in patients with Wnt-driven MB, we aimed to convert treatment-resistant MB subgroups into an ostensibly benign tumor through selective activation of the canonical Wnt pathway. Initial characterization of patient-derived Wnt and non-Wnt MB lines demonstrated a significant reduction in in vitro self-renewal and proliferative capacity of Wnt MBs. This was further validated by RNA-seq, which identified a marked reduction in the expression of stem cell self-renewal genes Bmi1 and Sox2 in Wnt MBs compared to non-Wnt MBs. Further, Wnt MB-derived xenografts maintained a significant increase in overall survival compared to non-Wnt MB xengrafts, further highlighting the protective nature of activated Wnt signaling in MB. Activated Wnt signaling by way of small molecule Wnt agonists in treatment-refractory MBs resulted in decreased in vitro self-renewal and expression of self-renewal genes, Bmi1 and Sox2. In order to validate the therapy-sensitive nature of Wnt-activated cells, we developed stable patient-derived lines containing a 7XTOPFlash reporter for endogenous Wnt signaling. Rare subclonal Wnt-active cells demonstrated a reduced self-renewal and tumor-initiating capacity through in vivo limiting dilution assays when compared to bulk Wnt-inactive cells. The therapeutic relevance of these findings were demonstrated with an in vivo survival advantage in those mice with orthotopic injections of cells with endogenous Wnt activity when compared to xenografts generated from Wnt-inactive cells. To develop a rationale clinical therapeutic, we used a novel substrate-competitive peptide inhibitor for GSK. Treatment with our peptide inhibitor showed a significant reduction in tumor burden with a corresponding increase in survival of patient-derived tumors that were otherwise treatment-resistant. The clinical utility of our findings is further supported by our analysis of integrated genomics data from 763 primary MBs, in which a validated Wnt gene signature was found to predict improved survivorship among children with poor-outcome and metastatic MBs. Our work establishes activated Wnt signaling as a novel treatment paradigm in childhood MB, identifies a rationale therapeutic approach for recurrent MB, and provides evidence for the context-specific tumor suppressive function of the canonical Wnt pathway. Citation Format: Sheila Kumari Singh, Branavan Manoranjan, Anna Dvorkin-Gheva, Chitra Venugopal, Steven Moreira, Michelle Kameda-Smith, Minomi Subapanditha, Ashley Adile, David Bakhshinyan, Neil Savage, Blake Yarascavitch, Olufemi Ajani, Adam Fleming, Bradley Doble. Canonical Wnt activation as a therapeutic strategy in pediatric medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 148.

The outcome of pediatric refractory or relapsed brain tumours remains a concern for treating neurooncology teams with the most effective salvage therapy yet to be established. Upfront therapy for primary medulloblastoma (MB) is dependent on age, post-operative residual and evidence of metastasis at diagnosis. Children diagnosed with aggressive subtypes of MB that are refractory to upfront therapy or recur either in the resection cavity or as distant metastases have a very poor prognosis. Reports of phase I and II studies for these children exist, but these therapies bear significant treatment related morbidity and mortality. A retrospective review of children diagnosed with a pediatric MB from 2002–2017 from the McMaster Pediatric Brain Tumour Study Group (PBTSG) captured a number of pediatric recurrent MB. Subsequently the treatments received and outcomes were identified. Over the 15-year period, 30 children with a histological diagnosis of MB were treated. Ten children were recurrent or treatment refractory MB. The 5-year outcome survival (OS) for this group of patients as compared to no recurrence was 20% and 90% respectively. The mean follow-up for survivors of recurrent MB however was 3.2 years. In 4 of 10 recurrent MB, the disease had significantly progressed and palliated. For the remaining children, therapy offered included cyberknife, imatinib, etoposide, vinblastine, temsirolimus, imatinib, tipifarnib, temozolamide, and irinotecan either in isolation or in varying combinations. Congruent to the literature, recurrent MB in our single center cohort carried a poor prognosis despite administration of salvage therapy.

Background: The surgical risk factors and neuro-imaging characteristics associated with cerebellar mutism (CM) remain unclear and require further investigation. We aimed to examine surgical and MRI findings associated with CM in children following posterior fossa tumor resection. Methods: Using our data registry, we retrospectively collected data from pediatric patients who acquired CM and were matched based on age and pathology type with patients not acquiring CM after posterior fossa surgery. The strength of association between surgical and MRI variables and CM were examined using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results: A total of 22 patients were included. Medulloblastoma was the most common pathology among CM patients (91%). Tumor attachment to the floor of the fourth ventricle (OR, 6; 95% CI, 0.7-276), calcification/hemosiderin deposition (OR 7; 95% CI 0.9-315.5), and post-operative peri-ventricular ischemia on MRI (OR, 5; 95% CI, 0.5-236.5) were found to have the highest association with CM. Conclusions: Our results may suggest that tumor attachment to the floor of the fourth ventricle, pathological calcification, and post-operative ischemia are relatively more prevalent in patients with CM. Collectively, our work calls for a larger multi-institutional study of CM patients to further investigate the determinants and management of CM to potentially minimize its development and predict onset.

Background: Cubital tunnel syndrome is the second most frequent upper extremity entrapment neuropathy. Various surgical approaches have been described in the literature for Ulnar nerve decompression, ranging from open In-situ decompression to endoscopic Ulnar nerve release. In this technical note we describe a new endoscopic approach for Ulnar nerve decompression. Methods: Four cadavers, a total of eight fresh arms were dissected using our new endoscopic technique. The technique involves a 2.5cm skin incision placed 2.5cm distal to the medial epicondyle, and perpendicular to the long nerve axis. Early identification of motor branches was achieved using this skin incision. Under endoscopic view using 30 degree rigid scope Ulnar nerves were decompressed Results: Early identification of motor branches was achieved using distally placed skin incision in all eight arms. Conclusions: The safety of identifying Ulnar nerve motor branches in the early steps of the procedure, and the avoidance of scar formation over the elbow joint are the proposed advantages of this approach. More clinical studies needed to validate this outcome.

Background: Cervical spine clearance protocols are controversial for unconscious patients after blunt traumatic injury and negative findings on computed tomography (CT). Purpose: To review evidence about the utility of different cervical spine clearance protocols in excluding significant cervical spine injury after negative CT results in obtunded adults with blunt traumatic injury. Data Sources: MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library were searched from January 2000 through November 2014. Study Selection: English-language studies that examined patients with negative CT results having confirmatory routine testing with magnetic resonance imaging (MRI), dynamic radiography, or clinical examination and that reported outcome measures of missed cervical spine injury, need for operative stabilization, or prolonged use of cervical collars. Data Extraction: Independent reviewers evaluated the quality of studies and abstracted the data according to a predefined protocol. Data Synthesis: Of 28 observational studies (3627 patients) that met eligibility criteria, 7 were prospective studies (1686 patients) with low risk of bias and well-interpreted, high-quality CT scans. These 7 studies showed that 0% of significant injuries were missed after negative CT results. The overall studies using confirmatory routine testing with MRI showed incidence rates of 0% to 1.5% for cervical spine instability (16 studies; 1799 patients), 0% to 7.3% for need for operative fixation (17 studies; 1555 patients), and 0% to 29.5% for prolonged collar use (16 studies; 1453 patients). Limitations: Most studies were retrospective. Approaches to management of soft tissue changes with collars varied markedly. Conclusion: Cervical spine clearance in obtunded adults after blunt traumatic injury with negative results from a well-interpreted, high-quality CT scan is probably a safe and efficient practice. Primary Funding Source: None.

Purpose: In an otherwise healthy patient with severe facial disfigurement secondary to burns, composite tissue allotransplantation (CTA) results in life-long immunosuppressive therapy and its associated risk. In this study, we assess the net gain of CTA of face (in terms of utilities) from the perspectives of patient, general public and medical expert, in comparison to the risks.Methods: Using the standard gamble (SG) and time-trade off (TTO) techniques, utilities were obtained from members of general public, patients With facial burns, and medical experts (n = 25 for each group). The gain (or loss) in utility and quality adjusted life years (QALY) were estimated using face-to-face interviews. A sensitivity analysis using variable life expectancy was conducted.Results: From the patient perspective, severe facial burn was associated with a health utility value of 0.53, and 27.1 QALYs as calculated by SG, and a health utility value of 0.57, and 28.9 QALYs as calculated by TTO. In comparison, CTA of the face was associated with a health utility value of 0.64, and 32.3 QALYs (or 18.2 QALYs years per sensitivity analysis) as calculated by SG, and a health utility value of 0.67, and 34.1 QALYs (or 19.2QALYs per sensitivity analysis) as calculated by TTO. However, a loss of 8.9 QALYs (by SG method) to 9.5 QALYs (by TTO method) was observed when the life expectancy was decreased in the sensitivity analysis. Similar results were obtained from the general population and medical experts perspectives.Conclusion: We found that severe facial disfigurement is associated with a significant reduction in the health-related quality of life, and CTA has the potential to improve this. Further, we found that a trade-off exists between the life expectancy and gain in the QALYs, i.e if life expectancy following CTA of face is reduced, the gain in QALY is also diminished. This trade-off needs to be validated in future studies. (C) 2015 Elsevier Ltd and ISBI. All rights reserved.