Midline Tumors Research Articles

Rational surgical neck management in total laryngectomy for advanced stage laryngeal squamous cell carcinomas

PurposeControversies exist in regard to surgical neck management in total laryngectomies (TL). International guidelines do not sufficiently discriminate neck sides and sublevels, or minimal neck-dissection nodal yield (NY).MethodsThirty-seven consecutive primary TL cases from 2009 to 2019 were retrospectively analyzed in terms of local tumor growth using a previously established imaging scheme, metastatic neck involvement, and NY impact on survival.ResultsThere was no case of level IIB involvement on any side. For type A and B tumor midline involvement, no positive contralateral lymph nodes were found. Craniocaudal tumor extension correlated with contralateral neck involvement (OR: 1.098, p = 0.0493) and showed increased involvement when extending 33 mm (p = 0.0134). Using a bilateral NY of ≥ 24 for 5-year overall survival (OS) and ≥ 26 for 5-year disease-free survival (DFS) gave significantly increased rate advantages of 64 and 56%, respectively (both p < 0.0001).ConclusionsThis work sheds light on regional metastatic distribution pattern and its influence on TL cases. An NY of n ≥ 26 can be considered a desirable benchmark for bilateral selective neck dissections as it leads to improved OS and DFS. Therefore, an omission of distinct neck levels cannot be promoted at this time.

Sentinel lymph node biopsy in muscle-invasive bladder cancer: single-center experience.

In this study, the validity of sentinel node biopsy procedure as our index test was assessed and compared with bilateral pelvic lymphadenectomy for staging and detecting the regional lymph nodes metastasis in patients with muscle-invasive bladder cancer (MIBC). Consecutive series of cases with T1-T4 urothelial MIBC were included. Following the injection of radiotracer, sentinel nodes were sought using a handheld gamma probe and all hot nodes were harvested. Bilateral pelvic lymphadenectomy was done for all patients following sentinel node biopsy. The tumor specimen, sentinel nodes, and excised lymph nodes were evaluated histopathologically. Same as the other midline tumors, detection rate and false negative rates were calculated using patient basis and side basis methods. By evaluating each patient as a unit of analysis, sentinel nodes were detected in 35 of 41 patients (85%), 13/16 (81%) of the neoadjuvant chemotherapy (NAC) and 22/25 (88%) of the no-neoadjuvant chemotherapy (No-NAC) participants. The false negative rate was 3/7 (42%): 1/3 (33%) for NAC, and 2/4 (50%) for No-NAC patients. By evaluating each hemipelvis as a unit of analysis, sentinel nodes were detected in 53 of 82 hemipelves (65%), 19/32 (66%) of the NAC, and 34/50 (68%) of the No-NAC hemipelves. No false-negative result was found by assessing each hemipelvis as a unit of analysis. Sentinel node biopsy is a feasible method for lymph node staging in MIBC, including patients with a history of NAC. To optimize the sensitivity, the decision regarding the lymphadenectomy is best to be based on the pathological status of sentinel node harvested from each hemipelvis separately as the unilateral finding of a sentinel node, does not rule out the possibility of metastatic involvement of contralateral pelvic lymph nodes.

Study of Supratentorial Tumours by Computed Tomography

Background: Brain neoplasms may be classified by the location of supratentorial, infratentorial and midline tumours. Of the supratentorial neoplasms, meningiomas are the most frequent extra-axial neoplasms. CT has become the most important diagnostic procedure in evaluating patients suspected of harboring an intracranial tumor. It is still considered the basic radiologic study since it gives specific information for the management of brain tumours and is minimally invasive. The purpose of this study was to assess the distribution, features, localization and extent of supratentorial neoplasms. Subjects and Methods: Fifty cases with symptoms of intracranial pathology and on CT found to have supratentorial tumours were studied. Results: The CT patterns of 50 supratentorial tumours were reviewed, out of which 30 cases i.e. 60%, were found to be intra- axial and 20 i.e. 40% extra-axial tumours. GBM formed the major group of the intra axial tumours i.e. 18 %, and meningiomas formed the major extra-axial tumours forming 26%. Conclusion: CT proves to be a valuable modality of imaging in evaluating the distribution, features, localizing and assessing the extent of various intra and extra-axial tumours in the supratentorial region.

MON-455 Papillary Thyroid Carcinoma in the Thyroglossal Duct

BACKGROUNDIn the thyroglossal duct (TD) there are remains of thyroid tissue in 1-40%. Thyroid cancer diagnosed in this duct is an uncommon finding, with a prevalence of less 1% and must meet these criteria: identify the TD, locate remains of carcinoma in it; absence of cancer in the thyroid gland and presence of thyroid follicles in the TD. We present a patient with thyroid cancer in the TD.CLINICAL CASE63-years-old-woman. 18 months ago, she noted a submandibular tumor associated to asthenia, weight loss and tremor. On physical examination: 3cm tumor, increased consistency, near to the hyoid bone and 1.5cm left cervical adenopathy. Blood analysis: TSH 0.01 (0.2-4.5) and FT4 5.53 (0.9-1.7). Hyperthyroidism was diagnosed and she started Tiamazol 10mg/bid and propanolol 20mg/tid.Thyroid US: diffuse goiter. Soft tissue US: heterogeneous mass 39x15x26mm in midline of suprathyroid region suggestive of neoformative process.Cervical CT scan: solid, heterogeneous, neoformative tissue, located in the midline, infiltrating prelaringeal muscles in contact with hyoid bone. Cervical adenopathy in group II on right side and group III and IV on the left side. Increase in thyroid gland volume.FNA US guided of suprathyroid tumor was performed: cytology compatible with papillary thyroid carcinoma, Bethesda VI. FNA left adenopathy: compatible with metastasis papillary carcinoma.Midline tumor exeresis in relation to a TD (Sistrunk surgery), total thyroidectomy plus left lymph node dissection group IIA, IIB, III, IV and V was performed.Surgical findings: Right lobe thyroid 4x3x2cm with 1cm nodule on the upper pole. Left thyroid lobe 6x4x2cm with multiple nodules, the largest one in upper pole, 2cm. Multiple adenopathies. A 3x3x1cm tumor with irregular edges, hard consistency, adhered to the hyoid bone was removed.The histology was compatible with papillary thyroid carcinoma in the TD. Thyroid gland was informed as simple goiter.150ug of levothyroxine was initiated. Six months later, she receives 100mCi I131. The total body scan was positive for thyroid remnant in cervical region. TSH 0.8 FT4 1.71. Thyroglobulin (TG) 13.98 and AntiTG 400.One year later, new total body scan was negative. TG 10,3 and antiTG 816. New thyroid US showed group III cervical adenopathy 4x7x3mm. Biopsy was compatible with metastasis of papillary thyroid carcinoma. The patient is awaiting a new surgery for lymph node dissection.CONCLUSIONSistrunk surgery and total thyroidectomy plus lymphadenectomy should be the treatment of choice in thyroid cancer in TD, followed by ablative therapy. This attitude improves long-term follow-up and reduces the risk of recurrence.BIBLIOGRAPHY1.Granado A, et al. Cáncer del conducto tirogloso. Acta Chir Catal, 8 (1987), 37-442.Echenique E. Thyroid cancer arising in a thyroglossal duct cyst. Cir Esp. 2000 67 (6) 567-71.

Radiological Evaluation of Newly Diagnosed Non-Brainstem Pediatric High-Grade Glioma in the HERBY Phase II Trial

The HERBY trial evaluated the benefit of the addition of the antiangiogenic agent Bevacizumab (BEV) to radiotherapy/temozolomide (RT/TMZ) in pediatric patients with newly diagnosed non-brainstem high-grade glioma (HGG). The work presented here aims to correlate imaging characteristics and outcome measures with pathologic and molecular data. Radiological, pathologic, and molecular data were correlated with trial clinical information to retrospectively re-evaluate event-free survival (EFS) and overall survival (OS). One-hundred thirteen patients were randomized to the RT/TMZ arm (n = 54) or the RT/TMZ+BEV (BEV arm; n = 59). The tumor arose in the cerebral hemispheres in 68 patients (Cerebral group) and a midline location in 45 cases (Midline group). Pathologic diagnosis was available in all cases and molecular data in 86 of 113. H3 K27M histone mutations were present in 23 of 32 Midline cases and H3 G34R/V mutations in 7 of 54 Cerebral cases. Total/near-total resection occurred in 44 of 68 (65%) Cerebral cases but in only 5 of 45 (11%) Midline cases (P < 0.05). Leptomeningeal metastases (27 cases, 13 with subependymal spread) at relapse were more frequent in Midline (17/45) than in Cerebral tumors (10/68, P < 0.05). Mean OS (14.1 months) and EFS (9.0 months) in Midline tumors were significantly lower than mean OS (20.7 months) and EFS (14.9 months) in Cerebral tumors (P < 0.05). Pseudoprogression occurred in 8 of 111 (6.2%) cases. This study has shown that the poor outcome of midline tumors (compared with cerebral) may be related to (1) lesser surgical resection, (2) H3 K27M histone mutations, and (3) higher leptomeningeal dissemination.

Sentinel lymph node mapping with fluorescent and radioactive tracers in vulvar cancer patients.

Application of radioactive tracers for sentinel lymph node biopsy (SLNB) in vulvar cancer has been established, however, the use of radioisotopes is expensive and requires complex logistics. This exploratory study evaluated the feasibility of near-infrared fluorescence-based SLNB in comparison to the gold standard using radioactive guidance. At Evangelische Kliniken Essen-Mitte (Essen, Germany) between 02/2015 and 04/2019, 33 patients with squamous cell vulvar cancer and unifocal tumors (32 midline, 1 lateral) smaller than 4cm underwent SLNB as part of their routine primary surgical therapy. Radiolabeled nanocolloid technetium 99 (99mTc) was injected preoperatively and indocyanine green (ICG) intraoperatively. Demographic and clinical data were retrieved from patients' records, and descriptive statistics were applied. The detection rate of the ICG fluorescence technique was compared with the standard radioactive approach. In patients with midline tumors, bilateral SLNB was attempted. SLNB was feasible in 61/64 (95.3%) groins with 99mTc and in 56/64 (87.5%) with ICG. In total, 125 SLNs were excised; all SLNs were radioactive and 117 (93.6%) also fluorescent. In 8 patients with BMI > 30kg/m2, SLNB was successful in 14/15 groins (93.3%) with 99mTc and 13/15 groins (86.7%) with ICG. Upon final histology, infiltrated nodes were present in 9/64 (14.1%) groins and 10/125 SLNs; one positive SLN was not detected with ICG. SLNB using ICG is a promising technique, however, the detection rate obtained was slightly lower than with 99mTc. The detection rate increased over time indicating that experience and training may play an important role besides further methodological refinements.

Endoscopic third ventriculostomy in posterior fossa tumor

Posterior fossa (PF) tumors are among the most frequent primary neoplasms in children. Proximity to the fourth ventricle, and therefore cerebrospinal fluid (CSF) pathways, predisposes children with PF tumors to the development of obstructive hydrocephalus. Some patients with PF tumors require a permanent CSF diversion procedure prior to or after tumor removal. However, management of hydrocephalus in children with resectable PF tumors is still controversial. In order to minimize the use of permanent shunts and to avoid associated complications, some investigators have advocated routine preoperative application of endoscopic third ventriculostomy (ETV) only in selected patients. We showed a clinical video case who experienced a preoperatively ETV before the surgical resection of their posterior fossa tumor. The patient is a 5 year-old boy presented with progressive headaches, vomits and somnolence. Young children with severe preoperative hydrocephalus and a midline tumor should be considered at risk when preoperative treatment decisions are made. *de Oliveira RS and Ballestero MFM contributed equally to this manuscript

INNV-28. MOLECULAR TESTING IN NEURO-ONCOLOGY – ASSESSMENT OF UTILITY AND PRACTICE PATTERNS. A SOCIETY FOR NEURO-ONCOLOGY MEMBERSHIP SURVEY

Abstract BACKGROUND Molecular testing (MT) is utilized in neuro-oncology with increasing frequency. Multiple molecular panels are available providing a spectrum of information. We were interested in learning how this information is acquired, what are the practice patterns regarding this type of testing, how are the results utilized in patient care and how prepared neuro-oncologists are to interpret these results. METHODS We conducted a survey using the Society for Neuro-Oncology membership database. We developed a set of 13 questions and administered the survey to 2022 members using the online platform. RESULTS We received 153 responses (7.5% of membership). 89% percent of responders routinely order MT. Of those who do not order MT on all patients, 50% test younger patients and 57% midline tumors. 83% use MT in recurrent glioma. Other common indications for MT included: metastatic tumors, meningioma, medulloblastoma, ATRT. Majority (60%) use in-house panels, followed by Foundation One (35%), TEMPUS (13%), CARIS (10%) and other panels (23%). For 57% of respondents, the data from MT was somewhat useful and for 41% it was very useful. 78% used the results of MT for clinical decision-making. BRAF, EGFR/ALK, H3K27 mutations were most commonly used for treatment decisions. 50% of respondents have molecular tumor boards at their institutions and a majority of practitioners share the results of MT with their patients (95%). Respondents would like to see SNO-endorsed official guidelines on MT, organized lists of targeted agents available for specific mutations, a database of targetable mutations and clinical trials and more educational programs on the subject. CONCLUSIONS Molecular testing is neuro-oncology is commonly done. Many providers rely on the information for clinical decision making where appropriate. In-house and commercial genetic panels are equally used in practice. There continues to be a need for more education on the subject and development of neuro-oncology specific guidelines.

PDTM-10. USE OF A NOVEL, HAND-HELD, ELECTRONIC DNA ANALYSIS PLATFORM TO QUANTIFY MULTI-GENE MOLECULAR RESPONSE IN CSF OF PATIENTS WITH HIGH-GRADE GLIOMA

Abstract BACKGROUND For midline tumors, surgical biopsy risks neurological injury. Non-invasive methods for diagnosis and surveillance are greatly needed. Tumors release DNA into cerebrospinal fluid (CSF-ctDNA), allowing for potential detection and serial monitoring of tumor-associated genetic mutations by CSF sampling. Current detection platforms are limited by their requirement for assay development for each mutation (digital droplet PCR), or cost and timeliness (Illumina sequencing). We hypothesized that direct, electronic analysis of CSF-ctDNA with a novel, hand-held platform (Oxford Nanopore MinION) could provide real-time, ultra-deep sequencing of patient-specific alterations in CSF-ctDNA. METHODS We established multiple clinical trials for pediatric high-grade glioma with required multi-time point (0, 2, and 6 month) correlate lumbar puncture (LP) at time of MRI, with accrual ongoing. We performed amplicon-based PCR on CSF-ctDNA for recurrent mutations and sequenced patient samples (tumor tissue n=8, tumor CSF n=60) and normal controls (tissue n=5, CSF n=24) using NanoPore technology. Variant allele fractions (VAF) were determined via MinKNOW, Guppy, MiniMap2, and Integrated Genome Browser. RESULTS Sensitivity was 79% and specificity 100% by NanoPore. Time from LP to results was 12 hours. A 17-year-old female presented with a biopsy-proven grade IV thalamic glioma with clonal mutations in H3F3A K27M, PIK3CA E545G, TP53 R158G, and TP53 R248Q. After failing standard treatment, she was enrolled in the ONC201 clinical trial and underwent serial LPs. MRI showed stable tumor at 2 months and 40% decrease at 6 months of treatment. H3K27M VAF increased from baseline at 2 months, but decreased to 1% at 6 months of treatment, results that were confirmed by ddPCR. PIK3CA E545G, TP53 R158G, and TP53 R248Q demonstrated the same decrease in VAF, with p-value of &lt; 0.0001. CONCLUSIONS We demonstrate a rapid, reliable method to detect tumor mutations in CSF, and further show molecular remission of H3K27M glioma by CSF sampling.

Imaging Characteristics of Wingless Pathway Subgroup Medulloblastomas: Results from the German HIT/SIOP-Trial Cohort.

In addition to the 4 histopathologically defined entities of medulloblastoma, 4 distinct genetically defined subgroups have been included in the World Health Organization classification of 2016. The smallest subgroup is the medulloblastoma with activated wingless pathway. The goal of this study was to identify a typical MR imaging morphology in a larger number of pediatric patients with wingless pathway medulloblastoma. From January 2001 to October 2017, of 75 patients with histologically confirmed and molecularly subgrouped wingless pathway medulloblastomas recruited to the German Pediatric Brain Tumor (HIT) trials, 38 patients (median age, 12.8 ± 4.6 years at diagnosis; 24 [63.2%] female) had preoperative imaging that passed the entry criteria for this study. Images were rated by the local standardized imaging criteria of the National Reference Center of Neuroradiology. Additionally, a modified laterality score was used to determine tumor localization and extension. Twenty-eight of 38 (73.7%) were primary midline tumors but with a lateral tendency in 39.3%. One extensively eccentric midline tumor was rated by the laterality score as in an off-midline position. Five tumors were found in the cerebellopontine angle; 3, in the deep white matter; and 2, in a cerebellar hemisphere. Leptomeningeal dissemination was rare (11.5%). In 60.5%, intratumoral blood-degradation products were found, and 26.3% showed cysts with blood contents. According to our observations, wingless pathway medulloblastomas are not preferentially off-midline tumors as postulated in previous studies with smaller wingless pathway medulloblastoma cohorts. Dense intratumoral blood-degradation products and cysts with blood contents are frequently found and might help to differentiate wingless pathway medulloblastoma from other medulloblastoma subtypes.

Predictors of Posterior Fossa Syndrome: Results From an International Multicenter Cohort Study of Molecularly Characterized Medulloblastoma Patients

Abstract INTRODUCTION Posterior Fossa Syndrome (PFS) is a common complication following surgical resection of pediatric posterior fossa tumors. PFS is characterized by a combination of mutism, ataxia, and other behavioral symptoms that typically improves within weeks to months. Medulloblastoma histology, midline location, and brainstem invasion increase risk for PFS. Medulloblastoma subgroups have historically been treated as a single entity when assessing PFS risk, however, recent studies highlighting their clinical heterogeneity suggest the need for a subgroup-specific analysis of PFS risk. Here, we examine a large international multicenter cohort of molecularly characterized medulloblastoma patients to assess predictors of PFS. METHODS We assembled a cohort of 270 medulloblastoma patients from 4 sites including Christian Medical College and Hospital (n = 87), Great Ormond Street Hospital (n = 25), Hospital for Sick Kids (n = 111), and Stanford University Medical Center (n = 47), who underwent surgical treatment of medulloblastoma and had molecular subgrouping of their tumors. Patient age at diagnosis, gender, tumor volume, and PFS status were assessed in addition to molecular subgroup. RESULTS Overall, 25.9% of our cohort developed PFS. PFS patients were younger (mean difference −2.73 yr ± 0.8, P = .0009) and had larger tumors (mean difference 16.99 cm3 ± 5.287, P = .0015) that were more midline (OR = 20.03, P &lt; .0001). On multivariate analysis adjusting for age, sex, midline location, and tumor volume, WNT (adjusted OR = 5.19, P = .022) and Group 4 (adjusted OR = 7.15, P = .004) tumors were found to be independently associated with higher risk of PFS as compared to SHH tumors. CONCLUSION Here, we present the largest molecularly characterized cohort of medulloblastoma patients in the context of PFS development. In combination with recent data showing that WNT and Group 4 tumors have a longer pre-diagnostic interval our results support the hypothesis that large midline tumors that grow slowly have a higher risk of PFS.

Extent of Resection, MGMT Promoter Methylation Status and Tumor Location Independently Predict Progression-Free Survival in Adult Sporadic Pilocytic Astrocytoma.

In adults, pilocytic astrocytomas (PA) account for less than 2% of gliomas, resulting in uncertainty regarding the clinical course and optimal treatment, particularly in cases where gross total resection (GTR) could not be achieved. Moreover, information on molecular markers and their prognostic impact is sparse. In order to improve risk stratification, we analyzed our institutional series of 58 patients aged 17 years and older with histology-proven intracranial PA World Health Organization grade I for clinical and molecular prognosticators. Anaplastic and NF1-associated tumors were excluded. O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was determined by pyrosequencing or 450k/850k DNA methylation array. A univariate log-rank test and multivariate StepAIC were applied to identify prognostic factors. The median age was 30 years (range 17–66). Tumors were located in the cerebral/cerebellar hemispheres, midline structures and cerebello-pontine angle in 53%, 38% and 9%. MGMT promoter methylation was present in eight patients (14%). GTR (39/58 patients) significantly reduced the likelihood of tumor recurrence (p = 0.0001). Tumor relapse occurred in 16 patients (28%) after a median progression-free survival (PFS) of 135 months (range 6–153 months); there was one tumor-related death. PFS at 5 and 10 years was 67% and 53%. In multivariate analysis, PFS was significantly prolonged in patients with GTR (HR 0.1; CI 0.03–0.37; p < 0.001), unmethylated MGMT promoter (HR 0.18; CI 0.05–0.64; p = 0.009) and midline tumors (HR 0.21; CI 0.06–0.78; p = 0.02). In conclusion, MGMT promoter methylation status and tumor location were identified as novel prognostic factors in adult PAs, pointing at distinct molecular subtypes and detecting patients in need of close observance and intensified treatment.

Retroperitoneal Sarcomas: Does Laterality Matter?

BackgroundSarcomas are malignant tumors of connective tissue that can vary widely in etiology. Parameters such as grade, extent of resection, and tumor integrity have been shown to affect prognosis. Our principal aim was to examine associations between the laterality of retroperitoneal sarcomas and tumor characteristics, treatment, and patient outcomes. Materials and methodsWe performed a retrospective study of patients treated at our tertiary referral center with a diagnosis of primary retroperitoneal sarcoma who underwent tumor resection. Categorical variables were compared using the chi-square test, whereas continuous variables were compared using one-way analysis of variance. Cox regression was used to estimate the risk of death. ResultsData from 106 patients were analyzed. A greater proportion of bilateral or midline tumors were leiomyosarcomas (P = 0.02), whereas right-sided tumors were more likely to be liposarcoma (P = 0.02). There was no significant relationship between laterality and tumor grade or stage. Two-thirds of patients had at least one contiguous organ resected (n = 68, 65.4%). Patients with nephrectomy during sarcoma resection were more likely to have right-sided disease (P = 0.02). Splenectomy and pancreatectomy were associated with left-sided disease (P < 0.01; P < 0.01), and pancreaticoduodenectomies with bilateral or midline disease (P < 0.001). Adjusting for age, sex, race, grade, stage, histology, and treatment, there was no increased risk of death or recurrence based on laterality. ConclusionsAlthough laterality did not seem to have a measurable relationship with patient outcomes or survival, there was a significant association between laterality, tumor histology, and resection of contiguous organs. These preliminary findings warrant further investigation.

Abstract SY44-02: Aberrant polycomb repression in midline and hindbrain tumors

Abstract The discovery of high-frequency histone H3 missense mutations (‘oncohistones’) in pediatric gliomas was the first time that histone mutations were linked to any disease. Since the original discovery, monoallelic missense mutations in genes encoding histone H3 have been found in a variety of cancer types. Previous studies have led to mechanistic insights into how one class of oncohistones promotes tumorigenesis by demonstrating that lysine-to-methionine (K-to-M) substitutions transform histones from serving as substrates into specific and potent inhibitors of lysine methyltransferases. Approximately 84% of diffuse intrinsic pontine glioma (DIPG) and 60% of high-grade non-brainstem pediatric midline gliomas contain a lysine 27-methionine (K27M) mutation. DIPG and other midline tumors have extremely low H3K27me3 levels caused by the action of the H3 K27M oncohistone. The H3 K27M protein binds to and inhibits the catalytic subunit (EZH2) of the Polycomb Repressive Complex 2 (PRC2), a conserved protein complex involved in gene silencing. Polycomb group (PcG) proteins are essential for development and are frequently misregulated in human cancers. Polycomb Repressive Complexes (PRC1, PRC2) function in a collaborative epigenetic cross-talk with H3K27me3 to initiate and maintain transcriptional silencing. Posterior fossa type A (PFA) ependymomas also exhibit very low H3K27 methylation but lack the K27M oncohistone. Instead, PFA tumors express high levels of KIP75 (K27M-like inhibitor of PRC2, 75kDa, also termed CXORF67). We find that a highly conserved sequence within the C-terminus of KIP75 is necessary and sufficient to inhibit the catalytic activity of PRC2 in vitro and in vivo. Our biochemical experiments indicate that KIP75 directly interacts with the active site of the EZH2 subunit in a mechanism that is remarkably similar to the K27M oncohistone. Furthermore, expression of H3 K27M or KIP75 promote similar chromatin landscapes and gene expression profiles in cell culture. Our data indicate that PFA ependymoma and DIPG tumors are driven in part by the action of peptidyl PRC2 inhibitors that dysregulate gene silencing to promote tumorigenesis. Citation Format: Peter W. Lewis. Aberrant polycomb repression in midline and hindbrain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY44-02.

Anatomical study in exposed area and operating space of extended endonasal approach to the ventral region of cranio-cervical junction

Objective To explore the scope, feasibility and indications of extended neuroendoscopic endonasal approach to reveal the region of cranial-cervical junction. Methods Ten (20 sides) intact frozen adult cadaveric heads were used to simulate the extended neuroendoscopic endonasal approach to remove the anterior tubercle of atlas, part of the atlas anterior arch, odontoid and part of the slope. In the cranial-cervical junction area, we observed the exposed range and measured the distance from the nostril to the anterior tubercle of atlas, the height and width of the anterior arch of the atlas, the distance of bilateral medial margin of occipital condyle, the distance of bilateral medial margin of the foramen lacerum, the vertical distance from the occipital condyle to the homolateral foramen lacerum, and the height, anteroposterior diameter and transverse diameter of the odontoid. Results The exposed range of the extended neuroendoscopic endonasal approach was as follows: when the lesion was located at the foramen magnum, the medial margin of the occipital condyle was the boundary of both sides, the root of the odontoid was the lower boundary, and the lower edge of the occipital bone was the upper boundary. When the lesion was located at the region of cranial-cervical junction, the upper edge of the foramen lacerum on both sides was the upper boundary, and the foramen lacerum and the outer edge of the occipital condyle were the boundaries of both sides of the bone window. By measurement, the distance from the nostril to the anterior tubercle of atlas was 8.9-9.7 cm, with an average of 9.3±0.3 cm. The height of the anterior arch of the atlas was 2.3-3.0 cm, with an average of 2.7±0.3 cm; the width was 1.5-2.0 cm, with an average of 1.8±0.2 cm; the distance of bilateral medial margin of occipital condyle was 1.5-2.0 cm, with an average of 1.8±0.2 cm; the distance of bilateral medial margin of the foramen lacerum was 2.1-2.9 cm, with an average of 2.4 ±0.3 cm; the vertical distance from the occipital condyle to the homolateral foramen lacerum was 1.6-2.2 cm, with an average of 1.9±0.3 cm; the height of the odontoid was 0.9-1.3 cm, with an average of 1.1±0.2 cm, its length was 0.8-1.3 cm, with an average of 1.1±0.2 cm; the transverse diameter of the dentate was 0.9-1.2 cm, with an average of 1.0±0.1 cm.The maximum exposed area of cranio-cervical junction was 6.4-9.8 cm2, with an average of 8.6±1.6 cm2. Conclusion The extended neuroendoscopic endonasal approach with removal of the anterior tubercle of atlas and part of the atlas anterior arch could effectively reveal the cranial-cervical junction area which is suitable for the treatment of odontoid deformity, skull base depression and atlantoaxial joint dislocation as well as resection of epidural tumors in the cranial-cervical junction and ventral and ventral midline tumors. Key words: Natural orifice endoscopic surgery; Anatomy; Cranio-cervical junction; Extended endonasal approach

Tumor location does not impact oncologic outcomes for percutaneous microwave ablation of clinical T1a renal cell carcinoma.

To evaluate the impact of anterior tumor location on oncologic efficacy, complication rates, and procedure duration for 151 consecutive biopsy-proven clinical T1a renal cell carcinoma (RCC) treated with percutaneous microwave (MW) ablation. This single-center retrospective study was performed under a waiver of informed consent. One hundred forty-eight consecutive patients (103 M/45 F; median age 67years, IQR 61-73) with 151 cT1a biopsy-proven RCC (median diameter 2.4cm, IQR 1.9-3.0) were treated with percutaneous MW ablation between March 2011 and August 2017. Patient and procedural data collected included Charlson comorbidity index (CCI), RENAL nephrometry score (NS), use of hydrodisplacement, MW antennas/generator output/time, and procedure time (PT). Data were stratified by anterior, posterior, and midline tumor location and compared with the Kruskal-Wallis or chi-squared tests. The Kaplan-Meier method was used for survival analyses. Tumor size, NS, and use/volume of hydrodisplacement were similar for posterior and anterior tumors (p> 0.05). Patients with anterior tumors had a higher CCI (3 vs 4, p= 0.001). Median PT for posterior and anterior tumors was similar (100 vs 108min, p= 0.26). Single session technical success and primary efficacy were achieved for all 151 tumors including 61 posterior and 67 anterior tumors. The 4 (3%) Clavien III-IV complications and 6 (4%) local recurrences were not associated with tumor location (p> 0.05). Three-year RFS, CSS, and OS were 95% (95% CI 0.87, 0.98), 100% (95% CI 1.0, 1.0), and 96% (95% CI 0.89, 0.98), respectively. The safety and efficacy of percutaneous microwave ablation for anterior and posterior RCC are similar. • The safety profile for percutaneous microwave ablation of anterior and posterior T1a renal cell carcinoma is equivalent. • Percutaneous microwave ablation of T1a renal cell carcinoma provides durable oncologic control regardless of tumor location. • Placement of additional microwave antennas and use of hydrodisplacement are associated with longer procedure times.

Long-term impairment of social behavior, vocalizations and motor activity induced by bilateral lesions of the fastigial nucleus in juvenile rats.

The cerebellum is increasingly recognized to be involved in limbic and cognitive-associative functioning. Cerebellar cognitiveaffective syndromes may result from various types of injuries. Cerebellar mutism may occur in children after resection of midline tumors in the posterior fossa, which has been thought to be related to damage to the cerebellar vermis. Here, we investigated whether bilateral lesions of the fastigial nucleus, which is located within the upper vermis, would affect social behavior in a rat model. Juvenile male Sprague-Dawley rats, aged 23days, underwent bilateral thermocoagulation of the fastigial nucleus via stereotaxically implanted electrodes under general anesthesia. Electrodes were inserted without application of electric current in a sham-lesion groupand naïve rats served as additional controls. All groups underwent standardized examination before surgery and on specific time points up to 49days after surgery to investigate locomotor activity, motor coordination, social behavior, and ultrasound vocalizations during social interaction. Finally, lesions were verified histologically. Playing behavior and vocalizations were reduced up to 4weeks after surgery in rats of the lesion group compared to rats with sham-lesions and controls. After surgery in rats of the lesion group, locomotor activity was disturbed for 3days as compared to sham-lesion rats, but for 4weeks as compared to controls. Motor coordination measured by the rotarod and balance beam test was compromised until adulthood. Bilateral lesions of the fastigial nucleus in juvenile rats cause a severe and long-lasting reduction of social interaction and motor coordination in juvenile rats, which has some similarities tocerebellar cognitiveaffective syndromes in the human context. This indicates a modulating role of the fastigial nucleus with regard to neural circuitries relevant for social behavior, such as the limbic system and the prefrontal cortex.

Treatment Strategies in Diffuse Midline Gliomas With the H3K27M Mutation: The Role of Convection-Enhanced Delivery in Overcoming Anatomic Challenges.

Diffuse midline gliomas harboring the H3 K27M mutation—including the previously named diffuse intrinsic pontine glioma (DIPG)—are lethal high-grade pediatric brain tumors that are inoperable and without cure. Despite numerous clinical trials, the prognosis remains poor, with a median survival of ~1 year from diagnosis. Systemic administration of chemotherapeutic agents is often hindered by the blood brain barrier (BBB), and even drugs that successfully cross the barrier may suffer from unpredictable distributions. The challenge in treating this deadly disease relies on effective delivery of a therapeutic agent to the bulk tumor as well as infiltrating cells. Therefore, methods that can enhance drug delivery to the brain are of great interest. Convection-enhanced delivery (CED) is a strategy that bypasses the BBB entirely and enhances drug distribution by applying hydraulic pressure to deliver agents directly and evenly into a target region. This technique reliably distributes infusate homogenously through the interstitial space of the target region and achieves high local drug concentrations in the brain. Moreover, recent studies have also shown that continuous delivery of drug over an extended period of time is safe, feasible, and more efficacious than standard single session CED. Therefore, CED represents a promising technique for treating midline tumors with the H3K27M mutation.

An anatomical study on the applicability of direct endoscopic exclusion of the ethmoid arteries for devascularization of the anterior skull base structures

The study was conducted on anatomical specimens of 12 cadaveric heads of deceased people without pathology of the anterior skull base structures, orbits, nasal cavity, and paranasal sinuses (24 sides). In all specimens, the internal and external carotid arteries were stained with silicone. During anatomical dissection, four surgical approaches for exclusion of the ethmoid arteries were studied: 1) transorbital approach to the arteries using a bicoronal incision; 2) endoscopic retro-caruncular approach; 3) endoscopic endonasal transethmoidal approach to the ethmoid artery canals; 4) endoscopic endonasal transethmoidal transorbital approach to the ethmoid arteries in the orbit. We described a surgical technique for exclusion of the ethmoid arteries using the approaches and analyzed their advantages and disadvantages. We formulated an algorithm for choosing the method for direct endoscopic exclusion of the ethmoid arteries, depending on the surgical approach chosen for removal of the tumor and features of the tumor extracranial spread. The decision on tumor devascularization is based on assessment of tumor blood supply (CT angiography or MR angiography data). Our study demonstrated the advantages and disadvantages of various approaches to the ethmoid arteries for their exclusion in order to early devascularize anterior skull base tumors. All these approaches are less traumatic and characterized by a good cosmetic and functional outcome.

Use of bevacizumab as a single agent or in adjunct with traditional chemotherapy regimens in children with unresectable or progressive low-grade glioma.

In pediatric low‐grade gliomas not amenable to complete resection, various chemotherapy regimens are the mainstream of treatment. An excellent overall survival of these patients makes justification of the intensification of chemotherapy difficult and calls for the development of new strategies. Bevacizumab, a humanized monoclonal antibody directed against Vascular endothelial growth factor (VEGF), has been successfully used in combination with irinotecan in a number of adult and pediatric studies and reports. Fifteen patients at median age of 7 years old (range 3 months to 15 years) were treated with bevacizumab in combination with conventional low‐toxicity chemotherapy. The majority had chiasmatic/hypothalamic and midline tumors, seven had confirmed BRAF pathway alterations including neurofibromatosis type 1 (2). Fourteen patients had more than one progression and three had radiotherapy. No deaths were documented, PFS at 11 and 15 months was 71.5% ± 13.9% and 44.7% ± 17.6% respectively. At the end of follow‐up 40% of patients has radiologically stable disease, three patients progressed shortly after completion of bevacizumab and two showed mixed response with progression of cystic component. Rapid visual improvement was seen in 6/8 patients, resolution of endocrine symptoms in 2/4 and motor function improvement in 4/6. No relation between histology or BRAF status and treatment response was observed. Treatment‐limiting toxicities included grade 4 proteinuria (2) and hypertension (2) managed with cessation (1) and pausing of therapy plus antihypertensives (1). In conclusion, bevacizumab is well tolerated and appears most effective for rapid tumor control to preserve vision and improve morbidity.