Recent advances in managing brain metastasis

Brain metastases are the most common malignancy encountered in the central nervous system (CNS), with up to 30-40% of cancer patients developing brain metastases at some point during the course of their disease. The management of brain metastasis is rapidly evolving and the roles of local therapies such as whole-brain radiation therapy, stereotactic radiosurgery, and resection along with systemic therapies are in flux. An emphasis on the neurocognitive side effects associated with treatment has gained prominence. Novel molecular studies have demonstrated important evolutionary patterns underpinning the development of brain metastasis and leptomeningeal disease, which may be key to unlocking new therapeutic strategies. This article provides a framework for incorporating the results of recent randomized radiotherapy clinical trials into practice, expounds upon the emphasis on cognition being an important driver in therapeutic selection, describes the importance of CNS-penetrating systemic therapies, and provides an overview of the novel molecular insights that will likely set the stage for future developments in this field

Effect of Postoperative Radiation Therapy Timing on Survival in Pediatric and Young Adult Ependymoma

Purpose Postoperative radiation therapy (RT) is commonly used for World Health Organization grade II-III intracranial ependymoma. Clinicians generally aim to begin RT ≤5 weeks after surgery, but postoperative recovery and need for second look surgery can delay the initiation of adjuvant therapy. On ACNS 0831, patients were required to enroll ≤8 weeks after initial surgery and begin adjuvant therapy within 3 weeks after enrollment. The purpose of this study was to determine the optimal timing of RT after surgery. Methods and Materials The National Cancer Database was queried for patients (aged 1-39 years) with localized World Health Organization grade II-III intracranial ependymoma treated with surgery and postoperative RT. Overall survival (OS) curves were plotted based on RT timing (≤5 weeks, 5-8 weeks, and \u3e8 weeks after surgery) and were compared by log-rank test. Factors associated with OS were identified by multivariate analysis. After 2009, complete data were available on whether patients underwent gross total resection or subtotal resection. Planned subset analysis was performed to examine the effect of RT timing on OS in patients with known extent of resection. Results In the final analytical data set of 1043 patients, no difference in 3-year OS was observed in patients who initiated RT ≤5 weeks, 5 to 8 weeks, and \u3e8 weeks after surgery (89.8% vs 89.1% vs 88.4%; P = .796). On multivariate analysis, grade III tumors (hazard ratio, 2.752; 95% confidence interval, 1.969-3.846, P \u3c .001) and subtotal resection (hazard ratio, 2.253; 95% confidence interval, 1.405-3.611, P \u3c .001) were significantly associated with reduced OS. Timing of RT, total RT dose, age, and other factors were not significant. These findings were affirmed in the subset of patients treated between 2010 and 2016, when extent of resection was routinely recorded. Conclusions Delayed postoperative RT was not associated with inferior survival in patients with intracranial ependymoma. Delayed RT initiation may be acceptable in patients who require longer postoperative recovery or referral to an appropriate RT center, but should be minimized whenever practical

A rare presentation of immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is defined as a hematologic disorder, characterized by isolated thrombocytopenia without any apparent cause. Some patients may be diagnosed during routine blood investigations or may present with bleeding diathesis. Treatment required for moderate to severe thrombocytopenia or those with bleeding manifestations. We present a case of 43 year old male, sputum positive pulmonary tuberculosis on isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) (HRZE) with persistent thrombocytopenia. He developed hepatitis hence isoniazid (INH) and rifampicin were stopped. He had fever, rash, purpura, hematuria and blood tinged sputum with platelet count of 10,000. 4 random donor platelets (RDPs) given. He suffered from mild COVID-19 infection and recovered in 2 weeks but platelets remained low. Bone marrow examination was suggestive of ITP. Inspite of steroid therapy no improvement was seen. Later was treated with injection romiplostim, and started on systemic lupus erythematosus (SLE) regimen for tuberculosis and discharged with regular follow up. Last platelet count being 1,20000/dl, liver function tests normal and now restarted on HRZE

Integration of Systemic Therapy and Stereotactic Radiosurgery for Brain Metastases

Abstract: Brain metastasis (BM) represents a common complication of cancer, and in the modern era requires multi-modal management approaches and multi-disciplinary care. Traditionally, due to the limited efficacy of cytotoxic chemotherapy, treatment strategies are focused on local treatments alone, such as whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and resection. However, the increased availability of molecular-based therapies with central nervous system (CNS) penetration now permits the individualized selection of tailored systemic therapies to be used alongside local treatments. Moreover, the introduction of immune checkpoint inhibitors (ICIs), with demonstrated CNS activity has further revolutionized the management of BM patients. The rapid introduction of these cancer therapeutics into clinical practice, however, has led to a significant dearth in the published literature about the optimal timing, sequencing, and combination of these systemic therapies along with SRS. This manuscript reviews the impact of tumor biology and molecular profiles on the management paradigm for BM patients and critically analyzes the current landscape of SRS, with a specific focus on integration with systemic therapy. We also discuss emerging treatment strategies combining SRS and ICIs, the impact of timing and the sequencing of these therapies around SRS, the effect of corticosteroids, and review post-treatment imaging findings, including pseudo-progression and radiation necrosis

Diabetic nephropathy: early markers for monitoring and prevention

Background: Type 2 diabetes, with its complications is perpetually on the rise more so in India .Diabetic Nephropathy progresses silently, and manifests at a stage where, patient can be offered only renal replacement. This study was undertaken to detect early markers of Diabetic Nephropathy. Aims and objective of the study was to study early nephropathy by UACR (urinary albumin/creatinine ratio), RFT (renal function test) and e-GFR in Type 2 diabetic patients of more than 2 years duration, with and without hypertension.Methods: A hospital based cross-sectional observational study, of 100 patients, 18-60 years of age, of type 2 Diabetes of 2 year duration and above, of which 50 were only diabetic and 50 had diabetes and hypertension. Patients who had an established renal disease were excluded from study.Results: Our study of 100 patients, 18-60 years of age, had 23 male and 77 female patients. Maximum patients were in age group 41-50 years, and 52% had diabetes of 2-4 years duration. Of the renal parameters studied, BUN was normal in 72% and S. Creatinine normal in 67%. UACR was normal in only 38%, and e-GFR was normal in 49%.Conclusions: In our study age and sex, duration of Diabetes and HbA1c did not have any bearing on renal parameters. UACR followed by e-GFR, were deranged early. UACR was more deranged in diabetics with hypertension.

Vision and Learning for Deliberative Monocular Cluttered Flight

Cameras provide a rich source of information while being passive, cheap and lightweight for small and medium Unmanned Aerial Vehicles (UAVs). In this work we present the first implementation of receding horizon control, which is widely used in ground vehicles, with monocular vision as the only sensing mode for autonomous UAV flight in dense clutter. We make it feasible on UAVs via a number of contributions: novel coupling of perception and control via relevant and diverse, multiple interpretations of the scene around the robot, leveraging recent advances in machine learning to showcase anytime budgeted cost-sensitive feature selection, and fast non-linear regression for monocular depth prediction. We empirically demonstrate the efficacy of our novel pipeline via real world experiments of more than 2 kms through dense trees with a quadrotor built from off-the-shelf parts. Moreover our pipeline is designed to combine information from other modalities like stereo and lidar as well if available

Integration of systemic therapy and stereotactic radiosurgery for brain metastases

Brain metastasis (BM) represents a common complication of cancer, and in the modern era requires multi-modal management approaches and multi-disciplinary care. Traditionally, due to the limited efficacy of cytotoxic chemotherapy, treatment strategies are focused on local treatments alone, such as whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and resection. However, the increased availability of molecular-based therapies with central nervous system (CNS) penetration now permits the individualized selection of tailored systemic therapies to be used alongside local treatments. Moreover, the introduction of immune checkpoint inhibitors (ICIs), with demonstrated CNS activity has further revolutionized the management of BM patients. The rapid introduction of these cancer therapeutics into clinical practice, however, has led to a significant dearth in the published literature about the optimal timing, sequencing, and combination of these systemic therapies along with SRS. This manuscript reviews the impact of tumor biology and molecular profiles on the management paradigm for BM patients and critically analyzes the current landscape of SRS, with a specific focus on integration with systemic therapy. We also discuss emerging treatment strategies combining SRS and ICIs, the impact of timing and the sequencing of these therapies around SRS, the effect of corticosteroids, and review post-treatment imaging findings, including pseudo-progression and radiation necrosis

Systematic review and meta-analysis of breast cancer brain metastasis and primary tumor receptor expression discordance

Background: Change in hormone receptor (estrogen [ER] and progesterone [PR]) and/or human epidermal growth factor receptor type 2 (HER2) status during the evolutionary course of metastatic breast cancer and the effect of tumor classification subtype switching remain understudied and underappreciated in brain metastasis patients. Methods: Using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a systematic review of series published prior to April 2020 obtained from the Medline database of biopsied or resected breast cancer brain metastasis (BCBM) was performed. Weighted random effects models were used to calculate pooled estimates. Results: 15 full-text articles were included with receptor expression analyses on 1373 patients who underwent biopsy or resection of at least one intracranial lesion to compare to the primary tumor. Primary tumor receptor expression immunophenotypes were 45.0% ER+, 41.0% ER-, 31.0% PR+, 51.0% PR-, 35% HER2+, and 47.0% HER2-. Corresponding BCBM immunophenotypes were 19.0% ER+, 31.0% ER-, 13.0% PR+, 40.0% PR-, 21.0% HER2+, and 26.0% HER2-. On primary/BCBM comparison, 540 patients (42.6%) exhibited discordance in any receptor with 17.0% (95% CI: 13.0%-23.0%) discordant on ER, 23.0% (95% CI: 18.0%-30.0%) discordant on PR, and 12.0% (95% CI: 8.0%-16.0%) discordant on HER2 status. The most common receptor conversions found in BCBM were ER loss 11.0% (95% CI: 8.0%-16.0%), PR loss 15.0% (95% CI: 11.0%-21.0%), and HER2 gain 9.0% (95% CI: 7.0%-11.0%). Conclusions: BCBM exhibits significant receptor expression discordance in comparison to primary tumors in approximately 40% of patients. Classification patterns need to be analyzed to determine factors predictive of BCBM/primary tumor discordance. Overall, tumor subtype switching and its effect on clinical management remains underappreciated. Keywords: HER2; breast cancer; discordance; estrogen receptor; progesterone receptor