Endoscopic Endonasal and Supraorbital Removal of Tuberculum Sellae Meningiomas: Anatomic Guides and Operative Nuances for Keyhole Approach Selection

BACKGROUND With growing worldwide endoscopy experience, endonasal and supraorbital removal of tuberculum sellae meningiomas (TSM) has increased. OBJECTIVE To describe anatomic factors for guiding approach selection and outcomes. METHODS Retrospective analysis of patients undergoing endonasal or supraorbital TSM resection: approach criteria, clinical outcomes, acute magnetic resonance imaging (MRI) fluid-attenuated inversion-recovery (FLAIR)/T2 changes. RESULTS From 2008 to 2020, 33 patients (mean age 55 ± 11 yr) were identified: 20 (61%) had endonasal and 13 (39%) supraorbital removal. Comparing endonasal and supraorbital approaches, mean tumor volume (3.7 ± 3.5 cm3 vs 7.7 ± 8.5 cm3, P = .07); percent tumor above planum (42% vs 65%, P = .02), and lateral tumor beyond supraclinoid internal carotid arteries (1.4 ± 2.0 mm vs 4.0 ± 3.2 mm, P = .006) were greater for supraorbital route. Sellar depth was greater for endonasal route tumors (12.2 ± 2.6 mm vs 9.3 ± 2.4 mm, P = .003). Endoscopy, used in 10/13(77%) supraorbital cases, was helpful in additional tumor removal in 4/10(40%). Gross total removal and mean volumetric tumor resection were 16/20(80%) and 97.5% by endonasal, and 5/13(39%) and 96% by supraorbital route. Vision improved in 12/17 (71%) endonasal, 6/8 (75%) supraorbital operations, and worsened in 1 (3%) supraorbital case. Endonasal approach with optic canal decompression increased over study period: 15/20 (75%) endonasal patients vs 1/13(8%) supraorbital (P < .001). Postoperative FLAIR/T2 MRI changes occurred in 2/12 supraorbital and 0/20 endonasal cases. CONCLUSION In our experience, both endonasal and supraorbital routes are safe and effective for TSM removal. Greater tumor extension below planum and medial optic canal invasion favor endonasal route, while larger size and lateral extension favor supraorbital route. Given high frequency of TSM growth into optic canals and better access for medial optic canal tumor removal, endonasal route may be preferred for most TSMs.

RONC-09. PSEUDOPROGRESSION AFTER PROTON THERAPY OF PEDIATRIC SPINAL PILOCYTIC ASTROCYTOMA AND MYXOPAPILLARY EPENDYMOMA

BACKGROUND Pseudoprogression after proton therapy of CNS tumors is a challenging clinical situation. The rate of pseudoprogression after proton therapy of pediatric spinal tumors is unknown. METHODS Records of pediatric patients with spinal pilocytic astrocytoma (sPA; n = 9) or myxopapillary ependymoma (MPE; n = 6) with gross disease treated with proton therapy with at least 6 months of follow up from completion of proton therapy were retrospectively reviewed for demographics, treatment characteristics, and occurrence of pseudoprogression. Pseudoprogression was defined as a post-radiation increase in tumor size with subsequent decrease in size without additional tumor-directed therapy. RESULTS The median age at radiation for sPA patients was 10.1y (range, 7.0 – 16.2y) and 12.7y (range, 7.9 – 14.4y) for MPE patients. The median prescribed dose was 45 GyRBE (range, 39.6 – 50.4 GyRBE) for sPA patients and 50.4 GyRBE (range, 45 – 54 GyRBE) for MPE patients. One sPA patient received concurrent vincristine. Median follow up after proton therapy was 44 months (range, 9 – 99 months). Six of nine sPA patients (67%) had pseudoprogression occurring at a median of 81 days (range, 34 – 136 days) after proton therapy; no MPE patients developed pseudoprogression (0%; p < 0.03). Two sPA patients with pseudoprogression were symptomatic and improved with medical therapy. CONCLUSION Preliminary analysis suggests that pseudoprogression occurs frequently within 6 months after proton therapy for sPA and infrequently after proton therapy for MPE.

Analysis of copy number alterations reveals the lncRNA ALAL-1 as a regulator of lung cancer immune evasion

Cancer is characterized by genomic instability leading to deletion or amplification of oncogenes or tumor suppressors. However, most of the altered regions are devoid of known cancer drivers. Here, we identify lncRNAs frequently lost or amplified in cancer. Among them, we found amplified lncRNA associated with lung cancer-1 (ALAL-1) as frequently amplified in lung adenocarcinomas. ALAL-1 is also overexpressed in additional tumor types, such as lung squamous carcinoma. The RNA product of ALAL-1 is able to promote the proliferation and tumorigenicity of lung cancer cells. ALAL-1 is a TNFα− and NF-κB–induced cytoplasmic lncRNA that specifically interacts with SART3, regulating the subcellular localization of the protein deubiquitinase USP4 and, in turn, its function in the cell. Interestingly, ALAL-1 expression inversely correlates with the immune infiltration of lung squamous tumors, while tumors with ALAL-1 amplification show lower infiltration of several types of immune cells. We have thus unveiled a pro-oncogenic lncRNA that mediates cancer immune evasion, pointing to a new target for immune potentiation.

Using Histopathology to Assess the Reliability of Intraoperative Magnetic Resonance Imaging in Guiding Additional Brain Tumor Resection: A Multicenter Study

BACKGROUND Intraoperative magnetic resonance imaging (iMRI) is a powerful tool for guiding brain tumor resections, provided that it accurately discerns residual tumor. OBJECTIVE To use histopathology to assess how reliably iMRI may discern additional tumor for a variety of tumor types, independent of the indications for iMRI. METHODS A multicenter database was used to calculate the odds of additional resection during the same surgical session for grade I to IV gliomas and pituitary adenomas. The reliability of iMRI for identifying residual tumor was assessed using histopathology of tissue resected after iMRI. RESULTS Gliomas (904/1517 cases, 59.6%) were more likely than pituitary adenomas (176/515, 34.2%) to receive additional resection after iMRI (P < .001), but these tumors were equally likely to have additional tissue sent for histopathology (398/904, 44.4% vs 66/176, 37.5%; P = .11). Tissue samples were available for resections after iMRI for 464 cases, with 415 (89.4%) positive for tumor. Additional resections after iMRI for gliomas (361/398, 90.7%) were more likely to yield additional tumor compared to pituitary adenomas (54/66, 81.8%) (P = .03). There were no significant differences in resection after iMRI yielding histopathologically positive tumor between grade I (58/65 cases, 89.2%; referent), grade II (82/92, 89.1%) (P = .98), grade III (72/81, 88.9%) (P = .95), or grade IV gliomas (149/160, 93.1%) (P = .33). Additional resection for previously resected tumors (122/135 cases, 90.4%) was equally likely to yield histopathologically confirmed tumor compared to newly-diagnosed tumors (293/329, 89.0%) (P = .83). CONCLUSION Histopathological analysis of tissue resected after use of iMRI for grade I to IV gliomas and pituitary adenomas demonstrates that iMRI is highly reliable for identifying residual tumor.

Expression Level and Clinical Significance of NKILA in Human Cancers: A Systematic Review and Meta-Analysis

Background. A number of researches focused on the study of tumors have concluded that the expression level of lncRNA NKILA was decreased in different tumors. This is an indication that NKILA might influence the start and growth of a cancer. In addition, studies have fatalities and worsening health of cancer patients is associated with a reduced level of NKILA. Results. The results are the collective screening of nine total studies which included 937 cancer patients. The prognosis of the meta-analysis indicated that cancer patients with a higher expression of NKILA had an overall longer survival (OS) (HR=0.808, 95% CI: 0.736, 0.887); with regard to the clinical prognosis, the results indicated that reduced NKILA was associated with advanced clinical stage (OR=0.313, 95% CI: 0.225, 0.434), poor histological grades (OR=0.833, 95% CI: 0.508, 1.367), positive lymph node metastasis (OR=0.253, 95% CI: 0.144, 0.444), and additional tumor invasion depth (OR=0.326, 95% CI: 0.234, 0.454). Materials and Methods. Related research conducted was accessed by searching in PubMed and Web of Science with the keywords. The accessed material was till the 25th of February, 2020. The present quantitative meta-analysis was done using Stata SE12.0. The aim of the meta-analysis was to investigate the relationship between NKILA expression level and clinical prognosis. Conclusions. In the result of this meta-analysis, decreased NKILA expression is typical of different kinds of cancer. Moreover, it can perform as a predictive element of prognosis in varied kinds of cancer. Nonetheless, till now, it is deemed essential to carry out larger-size as well as better designed research works for the confirmation of our findings.

NF-κB/Rel Transcription Factors in Pancreatic Cancer: Focusing on RelA, c-Rel, and RelB

Regulation of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/Rel transcription factors (TFs) is extremely cell-type-specific owing to their ability to act disparately in the context of cellular homeostasis driven by cellular fate and the microenvironment. This is also valid for tumor cells in which every single component shows heterogenic effects. Whereas many studies highlighted a per se oncogenic function for NF-κB/Rel TFs across cancers, recent advances in the field revealed their additional tumor-suppressive nature. Specifically, pancreatic ductal adenocarcinoma (PDAC), as one of the deadliest malignant diseases, shows aberrant canonical-noncanonical NF-κB signaling activity. Although decades of work suggest a prominent oncogenic activity of NF-κB signaling in PDAC, emerging evidence points to the opposite including anti-tumor effects. Considering the dual nature of NF-κB signaling and how it is closely linked to many other cancer related signaling pathways, it is essential to dissect the roles of individual Rel TFs in pancreatic carcinogenesis and tumor persistency and progression. Here, we discuss recent knowledge highlighting the role of Rel TFs RelA, RelB, and c-Rel in PDAC development and maintenance. Next to providing rationales for therapeutically harnessing Rel TF function in PDAC, we compile strategies currently in (pre-)clinical evaluation.

Dynamic Load Balancing Strategy for Parallel Tumor Growth Simulations

In this paper, we propose a parallel cellular automaton tumor growth model that includes load balancing of cells distribution among computational threads with the introduction of adjusting parameters. The obtained results show a fair reduction in execution time and improved speedup compared with the sequential tumor growth simulation program currently referenced in tumoral biology. The dynamic data structures of the model can be extended to address additional tumor growth characteristics such as angiogenesis and nutrient intake dependencies.

Evaluation of Biomarkers in Multiple Ipsilateral Synchronous Invasive Breast Carcinomas

Context.— The College of American Pathologists guidelines recommend testing additional tumor foci in multifocal invasive breast carcinomas for the biomarkers estrogen receptor (ER), progesterone receptor, and HER2 only if the carcinomas show different morphologies or grades. Objective.— To assess clinical significance of testing for biomarkers in additional tumor foci in multifocal invasive breast tumors. Design.— Retrospective analysis of 118 patients diagnosed with ipsilateral synchronous multifocal breast carcinomas from January 2015 through March 2016 at Mount Sinai Hospital (New York, New York). Results.— Eighty-six cases were tested for at least 1 of the 3 biomarkers in additional tumor foci. Fifteen cases (17%) showed discordant staining between the 2 foci for at least one biomarker. Of the 7 of 67 ER-discordant cases (10%), 4 (57%) showed major variation from negative to positive expression, including 3 cases in which a smaller tumor focus was strongly positive for ER whereas the index tumor was negative. Similarly, within the 7 of 67 progesterone receptor–discordant cases (10%), 4 (57%) showed major variation from negative to positive, and in 3 cases with major discordance, the index tumor was negative for progesterone receptor, whereas a smaller focus was positive. A difference in HER2 expression was noted in 5 of 86 cases (6%). In only 5 of the 15 patients (33%) with discordant results, biomarker testing on additional foci would have been offered per the College of American Pathologists recommendations because of differences in histology or grading. Of the remaining 10 patients, 7 (70%) with positive results on smaller foci would have been deprived of appropriate adjuvant systemic treatment if the smaller focus had not been tested. Conclusions.— We propose that negative values expressed in the primary tumor be repeated routinely on additional ipsilateral synchronous tumors.