RADT-03. OUTCOMES OF PATIENTS WITH HER2-POSITIVE BREAST CANCER METASTATIC TO BRAIN TREATED WITH HER2-TARGETED SYSTEMIC THERAPY AND STEREOTACTIC RADIOSURGERY

OBJECTIVE For patients with HER2-positive breast cancer metastatic to brain, HER2-directed systemic therapies are increasingly used with stereotactic radiosurgery (SRS). These include monoclonal antibodies such as trastuzumab (H) and pertuzumab (P), antibody-drug conjugates such as ado-trastuzumab emtansine (T-DM1), and tyrosine kinase inhibitors such as lapatinib. Limited data exist regarding appropriate timing with SRS and outcomes of this treatment regimen. METHODS A single-institution retrospective review collected clinical data on patients with breast cancer metastatic to brain who were treated with SRS from 2009-2020. Statistical analyses were performed using the Kaplan-Meier method and chi-square statistic. RESULTS Of 82 patients with breast cancer metastatic to brain treated with SRS, 33 (40%) were HER2-positive, 18 of whom were hormone receptor-positive. At brain metastasis diagnosis, 15 patients (45%) had >1 intracranial metastasis (range 2-7), and the median brain metastasis maximal dimension was 2.0 cm. Fifteen patients had uncontrolled extracranial disease. After brain metastasis diagnosis, 9 patients (27%) were treated with systemic therapy first (T-DM1+/-HP, lapatinib+HP, chemotherapy+/-HP) followed by SRS at a median of 18.6 months after starting systemic therapy. Seven patients (21%) were treated with SRS first, followed by systemic therapy in 6 of these patients (multi-agent regimens, 4 including T-DM1 or lapatinib). Seventeen (52%) received concurrent systemic therapy and SRS (T-DM1+/-chemotherapy, lapatinib, HP, hormone therapy, chemotherapy). Median follow-up time was 21.1 months. Median overall survival was 24.8 months and not statistically different between treatment groups. Four patients (12%) developed symptomatic radionecrosis; 3 were on T-DM1 concurrent with SRS. CONCLUSION In this small patient sample, we noted favorable survival outcomes for patients with HER2-positive breast cancer metastatic to brain when treated with HER2-targeted therapies together with SRS. The sequence of systemic therapy and SRS does not appear to impact survival outcomes. Concurrent treatment with T-DM1 and SRS may be associated with higher rates of radionecrosis.

Abstract 1122‐000052: Endovascular Management of Infectious PICA Aneurysm in the Setting of Recent Dental Work

Introduction : Infectious intracranial aneurysms (IIA) of the posterior inferior cerebellar artery (PICA) are exceedingly rare and have been infrequently reported. IIAs are typically distal and located in the anterior circulation, particularly the middle cerebral artery and its distal branches. Etiology is secondary to hematogenous spread of septic emboli from a proximal source such as infective endocarditis. Few cases have documented an association between IIA and dental disease or procedures. We describe a rare case of an infectious PICA aneurysm in the setting of recent dental work and successfully treated with endovascular intervention. Methods : An 88‐year‐old male with medical history of atrial fibrillation on anticoagulation presented with one month duration of recurrent falls and progressive generalized weakness. CT head demonstrated left cerebral hemorrhage with scattered subarachnoid hemorrhage. MRI brain noted a rounded enhancing intra‐axial lesion located at the left paramedian cerebellum measuring 7 mm in maximal dimension. Further investigation with cerebral angiography demonstrated an infectious intracranial aneurysm of the left PICA. He underwent workup with an echocardiogram that noted a mobile echo density on the aortic valve consistent with a vegetation. Blood cultures were positive for Streptococcus salivarius and viridans. Investigation revealed that he had recent dental work performed and missed taking his prophylactic amoxicillin. Infectious disease was consulted and etiology was determined to be seeding of aortic valve from recent dental procedure that ultimately led to IIA formation. Results : Patient was treated with 6‐week course of intravenous ceftriaxone and underwent glue embolization for his left PICA aneurysm. Post embolization angiogram did not reveal any evidence of contrast filling within the aneurysm. He tolerated the procedure well with no complications and was subsequently discharged to inpatient rehabilitation with a modified Rankin scale (mRS) score of 3. Conclusions : IIAs of PICA in the setting of recent dental procedures are exceptionally rare and challenging to diagnose. They may be clinically silent until rupture and are usually identified incidentally on imaging or during autopsy. Physicians should maintain vigilance for this unique entity as prompt recognition and timely intervention may prevent severe morbidity and mortality.

The Development of Large Radicular Cysts in Endodontically Versus Non-Endodontically Treated Maxillary Teeth

Background and Objectives: Large radicular cysts of the maxilla present a clinical challenge, as they may cause recurrent infection, severe alveolar bone loss and disruption of the nasal and maxillary sinus floors. The aim of this study was to evaluate the effect of previous root canal treatment on the clinical presentation of large maxillary radicular cysts. Materials and Methods: All cases of radicular cysts treated at the Oral and Maxillofacial Surgery Department of a tertiary public hospital over a period of six years (2012–2018) were evaluated. Histologically confirmed radicular cysts of the maxilla with a maximal dimension of over 15 mm were included. Demographic data of the patients, clinical presentation and radiographic features of the lesions were analyzed. Results: A total of 211 inflammatory cysts were treated in the study period, of these 54 histologically diagnosed radicular cysts in the maxilla were found to have a maximal dimension of over 15 mm. The mean age of patients with large maxillary radicular cysts was 43.3 years, 57.6% of which were male and 42.4% female. The lateral incisor was the most common tooth affected (46.3%). The mean size of the large radicular cysts was 25 mm. Then, 83.8% of the cysts were observed in teeth with previous endodontic treatment. Teeth without endodontic treatment presented clinically with significantly fewer acute symptoms in comparison to teeth with previous endodontic treatment. Conclusions: the vast majority (83.8%) of large maxillary radicular cysts were associated with endodontically treated teeth. Previous endodontic treatment was correlated to increased frequency of clinical symptoms.

Volumes of line bundles on schemes

The volume of a line bundle is an invariant defined in terms of a limit superior. It is a fundamental question whether this limit superior is a limit. It has been shown that this is always the case on generically reduced proper schemes over arbitrary fields. We show that volumes are limits in two classes of schemes that are not necessarily generically reduced: codimension one subschemes of projective varieties such that their components of maximal dimension contain normal points, and projective schemes whose nilradical squared equals zero.

Big and deep seated lipomatous tumours in children : results of surgical treatment

The objective of the study is aimed to evaluate results of our pediatric patients with big and deep-seated lipomatous tumors Results of 32 children who underwent resection for 5 cm or larger and deep-seated lipomas were evaluated. The mean age of the patients was 9.1 years (range, 0-16 ; 11 female/21 male), and median follow-up period was 3.21 years (range, 1-10 years). The median size of the excised tumour was 11 cm (range, 6-28 cm) in maximal dimension. Big lipomas in children can be treated with marginal resection procedures without biopsy with lower complication and local recurrence ratio compared to adult patients with similar tumours in similar size and location.

Centers and Azumaya loci for finite W-algebras in positive characteristic

In this paper, we study the center Z of the finite W-algebra $${\mathcal{T}}({\mathfrak{g}},e)$$ associated with a semi-simple Lie algebra $$\mathfrak{g}$$ over an algebraically closed field $$\mathbb{k}$$ of characteristic p≫0, and an arbitrarily given nilpotent element $$e \in{\mathfrak{g}} $$ We obtain an analogue of Veldkamp’s theorem on the center. For the maximal spectrum Specm(Z), we show that its Azumaya locus coincides with its smooth locus of smooth points. The former locus reflects irreducible representations of maximal dimension for $${\mathcal{T}}({\mathfrak{g}},e)$$ .

Pediatric lymphadenopathy: Which patients need evaluation by an oncologist?

e13605 Background: While lymphadenopathy may be the first sign of cancer in children, it can also be a manifestation of non-malignant illness. Lymphadenopathy is a common reason for referral to a pediatric oncologist, which can result in significant anxiety for parents. Understanding which patients require an oncology referral for lymphadenopathy is key in order to streamline healthcare utilization for this common clinical entity. Methods: In this single institution study, we retrospectively reviewed the medical records of patients referred to pediatric oncology for lymphadenopathy between 2012 and 2020. A logistic regression model was fitted to examine the association between the maximum size of the lymph nodes and cancer diagnosis. We also obtained estimates of odds ratio and area under the ROC curve. Sensitivity and specificity were estimated using exact Clopper-Pearson method for proportion. SAS v9.4 was used to perform statistical analyses. Institutional IRB approved the study. Results: A total of 91 patients aged 1 to 19 years (median 14 years) were included. There was a statistically significant association between lymph node size and a diagnosis of malignancy. For every centimeter increase in maximal dimension of lymph node(s), there was an estimated 2.2-times increase in the odds of cancer (CI 95% 1.5-3.3; p = 0.0002). The estimated area under the curve for this model was 0.8 (95% CI 0.7-0.9) indicating that lymph node size correlated very well with cancer risk. We evaluated the model to find a threshold for lymph node size that provided a high sensitivity for screening purposes. A cut-off of 2 centimeters resulted in an estimated sensitivity of 0.95 (95%CI 0.7-0.99) and specificity of 0.6 (95%CI 0.5-0.7). Conclusions: This study provides preliminary evidence that the estimated odds of a cancer diagnosis doubles for each centimeter increase in lymph node size. This single institution retrospective study suggests that in patients with lymphadenopathy, the maximum lymph node size may be a predictor of malignancy. Our results demonstrate that the sensitivity for cancer increases at a lymph node size of two centimeters or larger. Navigating when to monitor a patient with lymphadenopathy in the primary care setting versus referring to the oncologist can be a challenge for primary care physicians. Our results are consistent with the practice that using a two centimeter cutoff is a good starting point for referrals; however, these results will need to be verified with a larger sample size before they are adopted into clinical guidelines. Further study is underway to evaluate lymphadenopathy referrals to both surgery and oncology in order to reduce potential bias that may be associated with oncology referrals, which may have a predilection for malignancy. This study underlines the importance of a physical examination by the primary care physician as the crucial step in determining if a patient requires an oncology referral.

Aortic root measurement on CT: linear dimensions, aortic root area and comparison with echocardiography. A retrospective cross sectional study

Objective: We sought to assess the different CT aortic root measurements and determine their relationship to transthoracic echocardiography (TTE). Methods: TTE and ECG-gated CT images were reviewed from 70 consecutive patients (mean age 54 ± 18 years; 67% male) with tricuspid aortic roots (trileaflet aortic valves) between Nov 2009 and Dec 2013. Three CT planes (coronal, short axis en face and three-chamber) were used for measurement of nine linear dimensions. TTE aortic root dimension was measured as per guidelines from the parasternal long axis view. Results: All CT short axis measurements of the aortic root had excellent reproducibility (intraclass correlation coefficient, ICC 0.96–0.99), while coronal and three-chamber planes had lower reproducibility with ICC 0.90 (95% CI 0.84–0.94) and ICC 0.92 (0.87–0.95) respectively. CT coronal and short axis maximal dimensions were systematically larger than TTE (mean 2 mm larger, p < 0.001), while CT cusp to commissure measurements were systematically smaller (CT RCC-comm mean 2 mm smaller than TTE, p < 0.001). All CT short axis measurements had excellent correlation with aortic root area with CT short axis maximal dimension marginally better than the rest (Pearson’s R 0.97). Conclusion: Systematic differences exist between CT and TTE dependent on the CT plane of measurement. All CT short axis measurements of the aortic root had excellent reproducibility and correlation with aortic root area with maximal dimension appearing marginally better than the rest. Our findings highlight the importance of specifying the chosen plane of aortic root measurement on CT. Advances in knowledge: Systematic differences in aortic root dimension exist between TTE and the various CT measurement planes. CT coronal and short axis maximal dimensions were systematically larger than TTE, while CT cusp to commissure measurements were smaller. CT readers should indicate the plane of measurement and the specific linear dimension to avoid ambiguity in follow-up and comparison.

Absolute parallelism for 2-nondegenerate CR structures via bigraded Tanaka prolongation

This article is devoted to the local geometry of everywhere 2-nondegenerate CR manifolds M of hypersurface type. An absolute parallelism for such structures was recently constructed independently by Isaev and Zaitsev, Medori and Spiro, and Pocchiola in the minimal possible dimension ( dim ⁡ M = 5 {\dim M=5} ), and for dim ⁡ M = 7 {\dim M=7} in certain cases by the first author. In the present paper, we develop a bigraded (i.e., ℤ × ℤ {\mathbb{Z}\times\mathbb{Z}} -graded) analog of Tanaka’s prolongation procedure to construct an absolute parallelism for these CR structures in arbitrary (odd) dimension with Levi kernel of arbitrary admissible dimension. We introduce the notion of a bigraded Tanaka symbol – a complex bigraded vector space – containing all essential information about the CR structure. Under the additional regularity assumption that the symbol is a Lie algebra, we define a bigraded analog of the Tanaka universal algebraic prolongation, endowed with an anti-linear involution, and prove that for any CR structure with a given regular symbol there exists a canonical absolute parallelism on a bundle whose dimension is that of the bigraded universal algebraic prolongation. Moreover, we show that for each regular symbol there is a unique (up to local equivalence) such CR structure whose algebra of infinitesimal symmetries has maximal possible dimension, and the latter algebra is isomorphic to the real part of the bigraded universal algebraic prolongation of the symbol. In the case of 1-dimensional Levi kernel we classify all regular symbols and calculate their bigraded universal algebraic prolongations. In this case, the regular symbols can be subdivided into nilpotent, strongly non-nilpotent, and weakly non-nilpotent. The bigraded universal algebraic prolongation of strongly non-nilpotent regular symbols is isomorphic to the complex orthogonal algebra 𝔰 ⁢ 𝔬 ⁢ ( m , ℂ ) {\mathfrak{so}(m,\mathbb{C})} , where m = 1 2 ⁢ ( dim ⁡ M + 5 ) {m=\tfrac{1}{2}(\dim M+5)} . Any real form of this algebra – except 𝔰 ⁢ 𝔬 ⁢ ( m ) {\mathfrak{so}(m)} and 𝔰 ⁢ 𝔬 ⁢ ( m - 1 , 1 ) {\mathfrak{so}(m-1,1)} – corresponds to the real part of the bigraded universal algebraic prolongation of exactly one strongly non-nilpotent regular CR symbol. However, for a fixed dim ⁡ M ≥ 7 {\dim M\geq 7} the dimension of the bigraded universal algebraic prolongations of all possible regular CR symbols achieves its maximum on one of the nilpotent regular symbols, and this maximal dimension is 1 4 ⁢ ( dim ⁡ M - 1 ) 2 + 7 {\frac{1}{4}(\dim M-1)^{2}+7} .

Big and deep seated lipomatous tumours in children : results of surgical treatment

The objective of the study is aimed to evaluate results of our pediatric patients with big and deep-seated lipomatous tumors Results of 32 children who underwent resection for 5 cm or larger and deep-seated lipomas were evaluated. The mean age of the patients was 9.1 years (range, 0-16 ; 11 female/21 male), and median follow-up period was 3.21 years (range, 1-10 years). The median size of the excised tumour was 11 cm (range, 6-28 cm) in maximal dimension. Big lipomas in children can be treated with marginal resection procedures without biopsy with lower complication and local recurrence ratio compared to adult patients with similar tumours in similar size and location.