scholarly journals DIPG-01. REIRRADIATION PRACTICES FOR DIFFUSE INTRINSIC PONTINE GLIOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii287-iii287
Author(s):  
Chantel Cacciotti ◽  
Kevin Liu ◽  
Daphne Haas-Kogan ◽  
Katherine Warren
Keyword(s):  
Treatment Option ◽  
Clinical Status ◽  
Standard Of Care ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Current Standard ◽  
Radiation Oncologists ◽  
Concurrent Use ◽  
Median Total Dose ◽  
Diffuse Intrinsic Pontine Gliomas ◽  
One Year

Abstract INTRODUCTION Diffuse intrinsic pontine gliomas (DIPG) are a leading cause of brain tumor deaths in children. Current standard of care includes focal radiation therapy (RT). Despite clinical improvement in the majority of patients, the effect is temporary and median survival is less than one year. The use of reirradiation and possible benefit has been reported in progressive DIPG, yet standardized approaches are lacking. We conducted an internet-based survey to assess physicians’ practices in pediatric DIPG. METHODS A 14-question REDCap survey regarding re-irradiation practices was emailed to 396 physicians identified through an International Pediatric Neuro-Oncology and Radiation-Oncology database. RESULTS Response rate was 35% overall (radiation-oncologists, 28%; pediatric oncologists, 57%). Two participants were excluded (did not treat DIPG). Participants included radiation-oncologists (62%), pediatric oncologists (7%), and pediatric neuro-oncologists (29%). Most physicians (62%) treated 1–5 DIPG patients per year, with 10% treating >10/year. Reirradiation was considered a treatment option in 88%. Progressive disease or worsening clinical status were the most common reasons to consider reirradiation. The majority (84%) considered reirradiation a minimum of 6 months following initial RT. Doses varied, with median total dose 24Gy (range 12–60); 2Gy/fraction (range 1–9). Concurrent use of systemic agents with reirradiation was considered in 46%, mainly with targeted agents (37%), biologics (34%), or immunotherapy (25%). One-time reirradiation was the most common practice (71%). Interestingly, 9% of respondents would not consider reirradiation. CONCLUSION Although, the vast majority of physicians agree with re-irradiation as a treatment option for DIPG the total doses varied, and further clinical trials are needed.

scholarly journals Reirradiation practices for children with diffuse intrinsic pontine glioma

2020 ◽  
Author(s):  
Chantel Cacciotti ◽  
Kevin X Liu ◽  
Daphne A Haas-Kogan ◽  
Katherine E Warren
Keyword(s):  
Progressive Disease ◽  
Response Rate ◽  
Clinical Status ◽  
Standard Of Care ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Current Standard ◽  
Concurrent Use ◽  
Median Total Dose ◽  
Diffuse Intrinsic Pontine Gliomas ◽  
Systemic Agents

Abstract Background Diffuse intrinsic pontine gliomas (DIPGs) are a leading cause of brain tumor deaths in children. Current standard of care includes focal radiation therapy (RT). Despite clinical improvement in most patients, the effect is temporary and median survival is less than 1 year. The use and benefit of reirradiation have been reported in progressive DIPG, yet standardized approaches are lacking. We conducted a survey to assess reirradiation practices for DIPG in North America. Methods A 14-question REDCap survey was disseminated to 396 North American physicians who care for children with CNS tumors. Results The response rate was 35%. Participants included radiation-oncologists (63%; 85/135) and pediatric oncologists/neuro-oncologists (37%; 50/135). Most physicians (62%) treated 1 to 5 DIPG patients per year, with 10% treating more than 10 patients per year. Reirradiation was considered a treatment option by 88% of respondents. Progressive disease and worsening clinical status were the most common reasons to consider reirradiation. The majority (84%) surveyed considered reirradiation a minimum of 6 months following initial RT. Doses varied, with median total dose of 2400 cGy (range, 1200-6000 cGy) and fraction size of 200 cGy (range, 100-900 cGy). Concurrent use of systemic agents with reirradiation was considered in 46%, including targeted agents (37%), biologics (36%), or immunotherapy (25%). One-time reirradiation was the most common practice (71%). Conclusion Although the vast majority of physicians consider reirradiation as a treatment for DIPG, total doses and fractionation varied. Further clinical trials are needed to determine the optimal radiation dose and fractionation for reirradiation in children with progressive DIPG.

scholarly journals Neurokinin-1 receptor (NK-1R) antagonists: potential targets in the treatment of glioblastoma multiforme

2021 ◽  
Vol 28 ◽  
Author(s):  
Amir R. Afshari ◽  
Ali Motamed-Sanaye ◽  
Hamed Sabri ◽  
Arash Soltani ◽  
Sepideh Karkon-Shayan ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Standard Of Care ◽  
Therapeutic Approaches ◽  
Current Standard ◽  
Cancer Cell Growth ◽  
Neurokinin 1 Receptor ◽  
The Family ◽  
Substantial Progress ◽  
Neurokinin 1 ◽  
One Year

: The current standard of care in glioblastoma multiforme (GBM), as the most morbid brain tumor, is not adequate, despite substantial progress in cancer therapy. Among patients receiving current standard treatments, including surgery, irradiation, and chemotherapy, the overall survival (OS) period with GBM is less than one year. The high mortality frequency of GBM is due to its aggressive nature, including accelerated growth, deregulated apoptosis, and invasion into surrounding tissues. The understanding of the molecular pathogenesis of GBM is, therefore, crucial for identifying, designing, and repurposing potential agents in future therapeutic approaches. In recent decades, it has been apparent that several neurotransmitters, specifically substance P (SP), an undecapeptide in the family of neuropeptides tachykinins, are found in astrocytes. After binding to the neurokinin-1 receptor (NK-1R), the SP controls cancer cell growth, exerts antiapoptotic impacts, stimulates cell invasion/metastasis, and activates vascularization. Since SP/NK-1R signaling pathway is a growth driver in many cancers, this potential mechanism is proposed as an additional target for treating GBM. Following an evaluation of the function of both SP and its NK-1R inhibitors in neoplastic cells, we recommend a unique and promising approach for the treatment of patients with GBM.

Ultrasonography

2019 ◽  
pp. 808-815
Author(s):  
Santiago Naranjo-Sierra ◽  
Lauren K. Ng Tucker
Keyword(s):  
Intensive Care Unit ◽  
Emergency Medicine ◽  
Visual Information ◽  
Point Of Care ◽  
Clinical Status ◽  
Standard Of Care ◽  
Sound Waves ◽  
Current Standard ◽  
Point Of Care Ultrasonography ◽  
Management Changes

Ultrasonography is the use of sound waves to create images and is used mainly for diagnostic purposes and for real-time guidance during procedures. Point-of-care ultrasonography is widely used in fields such as anesthesia, critical care, and emergency medicine, in which it is becoming an important part of the current standard of care because of its ability to provide accurate visual information about a patient, either to rapidly evaluate clinical status or to provide guidance for procedures, without requiring transfers to other areas. For patients in an intensive care unit, focused ultrasonography has been reported to result in management changes in more than 50%.

scholarly journals 39. CHARACTERIZING NOVEL INHIBITORS OF BRAIN METASTASIS-INITIATING CELLS

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii7-ii7
Author(s):  
Agata Kieliszek ◽  
Chitra Venugopal ◽  
Blessing Bassey-Archibong ◽  
Nikoo Aghaei ◽  
Fred Lam ◽  
...  
Keyword(s):  
At Risk ◽  
Brain Metastasis ◽  
Primary Tumor ◽  
Unmet Need ◽  
Standard Of Care ◽  
Current Standard ◽  
One Year ◽  
Pdx Models

Abstract BACKGROUND The incidence of brain metastases (BM) is tenfold higher than primary brain tumors. BM commonly originate from primary lung, breast, and melanoma tumors with a 90% mortality rate within one year of diagnosis. Current standard of care for BM includes surgical resection with concurrent chemoradiation, but does not extend median survival past 16 months, posing a large unmet need to identify novel therapies against BM. METHODS From a large in-house biobank of patient-derived BM cell lines, the Singh Lab has generated murine orthotopic patient-derived xenograft (PDX) models of lung, breast, and melanoma BM that recapitulate the stages of BM progression as seen in human patients. Using these three PDX models, we identified a population of “pre-metastatic” brain metastasis-initiating cells (BMICs) that are newly arrived in the brain but have yet to form detectable tumors. Pre-metastatic BMICs are not detectable in human patients but are important therapeutic targets with the potential to prevent BM in at-risk patients. RESULTS RNA sequencing of pre-metastatic BMICs from all three PDX primary tumor models with subsequent Connectivity Map analysis identified novel compounds that have the potential of killing all three types of BMICs. In particular, we identified two compounds that have selective killing of BMICs in vitro from all three primary tumor cohorts while sparing non-cancerous cells. We further characterized their ability to inhibit the self-renewal and proliferative properties of BMICs. Ongoing in vivo work will investigate the compounds’ preclinical utilities in preventing BM. CONCLUSION Identification of novel small molecules that target BMICs could prevent the formation of BM completely and dramatically improve the prognosis of at-risk cancer patients.

scholarly journals DIPG-57. TRANSCRIPTOMIC AND PROTEOMIC ANALYSES OF DIPG RESPONSE TO ONC201

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii298-iii298
Author(s):  
Sreepradha Sridharan ◽  
Arif Harmanci ◽  
Ajay Sharma ◽  
Yanlai Lai ◽  
Bridget Kennis ◽  
...  
Keyword(s):  
Intraperitoneal Administration ◽  
Pediatric Brain Tumor ◽  
Standard Of Care ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Tumor Burden ◽  
Current Standard ◽  
Extrinsic Factors ◽  
Altered Expression ◽  
Ic50 Values

Abstract Diffuse Intrinsic Pontine Glioma (DIPG) is an incurable pediatric brain tumor. Current standard of care has shown no improvements in survival. Here, we report our study of ONC201, a first-in-class small molecule developed by Oncoceutics, Inc., against a panel of DIPG cells in vitro and in mouse orthotopic models. ONC201 inhibits signaling through dopamine receptor D2 (DRD2), a G protein-coupled receptor (GPCR). MTT assays revealed a delayed but more robust response to ONC201, as measured by IC50 values, in DIPGs with histone H3.3-K27M expression compared to cells expressing wildtype (WT) or K27M mutant histone H3.1. Interestingly, transcriptomic profiling identified an association of this response delay with an elevation of genes controlling the cellular unfolded protein response, lysosomal and vacuole organization, and a decline in nucleic acid biosynthetic genes. These cells were also more committed to neuronal and oligodendrocytic lineage specification. By contrast, WT-H3 DIPGs that survived ONC201 treatment were stem-like and exhibited altered expression of genes controlling cell proliferation and apoptosis induction, respectively. Single cell proteomics validated the increase in anti-apoptotic proteins in these cells. Intraperitoneal administration of ONC201 for 7-weeks in mice bearing pontine xenografts of histone H3.1-K27M mutant DIPGs, caused a complete blockade of tumor growth relative to untreated controls. However, identical treatment of animals with forebrain tumors resulted only in a partial reduction in tumor burden, suggesting that the tumor microenvironment may be involved in the differential effect. These data indicate that tumor intrinsic and extrinsic factors may contribute to the response of DIPG tumors to ONC201.

scholarly journals Effectiveness of dalbavancin compared to standard of care for the treatment of osteomyelitis: A real world analysis

2021 ◽  
Author(s):  
Alexander R Cain ◽  
Derek N Bremmer ◽  
Dustin R Carr ◽  
Carley Buchanan ◽  
Max Jacobs ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Failure ◽  
Treatment Options ◽  
Standard Of Care ◽  
Hospital Length ◽  
Primary Objective ◽  
Hospital Length Of Stay ◽  
Current Standard ◽  
Index Site ◽  
One Year

Abstract Background Preliminary data suggest that the effectiveness of dalbavancin may be similar to current standard of care (SoC) treatment options for osteomyelitis with an advantageous dosing schedule. Methods This was a retrospective, observational cohort study of adult patients diagnosed with osteomyelitis. Patients were matched 1:2 to dalbavancin (administered as 2 doses separated by 1 week) or SoC treatment for osteomyelitis according to Charlson Comorbidity Index, site of infection, and causative pathogen. The primary objective was to determine the incidence of treatment failure after a one-year follow-up period. Secondary objectives included hospital length of stay (LOS), infection-related one-year readmission rates, and treatment-related adverse events. Results A total of 132 patients received dalbavancin (n = 42) or SoC (n = 90). Baseline characteristics, including the rates of surgical intervention, were similar between the two treatment groups. Treatment failure was similar between those who received dalbavancin and SoC (21.4% vs 23.3%, p = 0.81). Patients who received dalbavancin had a shorter hospital LOS (5.2 days vs 7.2 days, p = 0.01). There was no difference in the rates of infection-related readmission between the dalbavancin and the SoC group (31% vs 31.1%, p = 0.99). There were numerically fewer adverse events in the dalbavancin group compared to the SoC group (21.4% vs 36.7%, p = 0.08). Peripherally inserted central catheter line related complications were reported in 17.8% of patients in the SoC group. Conclusions Dalbavancin administered as a two-dose regimen is a safe and effective option for the treatment of osteomyelitis.

scholarly journals 108. Efficacy of Dalbavancin Compared to Standard of Care for the Treatment of Osteomyelitis: A Retrospective Study

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S67-S67
Author(s):  
Alexander Cain ◽  
Derek N Bremmer ◽  
Dustin R Carr ◽  
Carley Buchanan ◽  
Max Jacobs ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Failure ◽  
Treatment Options ◽  
Standard Of Care ◽  
Hospital Length ◽  
Primary Objective ◽  
Hospital Length Of Stay ◽  
Current Standard ◽  
Index Site ◽  
One Year

Abstract Background Preliminary data suggest that the efficacy of dalbavancin, a long-acting lipoglycopeptide, may be similar to current standard of care (SoC) treatment options for osteomyelitis, and may be associated with fewer treatment related adverse events. This study assessed the incidence of treatment failure in patients receiving either dalbavancin or SoC for the treatment of osteomyelitis. Methods This was a multi-center, retrospective, observational cohort study of adult patients diagnosed with osteomyelitis. Patients were matched 1:2 to either dalbavancin (1500 mg infused intravenously on days 1 and 8) or SoC for osteomyelitis (oral or intravenous antibiotics) by Charlson Comorbidity Index, site of infection, and causative pathogen. The primary objective was to determine the incidence of treatment failure after a one-year follow-up period. Secondary objectives included hospital length of stay (LOS), infection related one-year readmission rates, and treatment related adverse events. Results A total of 132 patients were matched to receive dalbavancin (n = 42) or SoC (n = 90). Baseline characteristics were similar between the two treatment groups. The majority of patients had lower extremity osteomyelitis (76.2% vs 73.3%) with an etiology of diabetic foot infection (45.2% vs 46.7%) in the dalbavancin and SoC groups, respectively. Treatment failure was similar between those who received dalbavancin and SoC (21.4% vs 23.3%, p = 0.808). Patients who received dalbavancin had a significantly shorter hospital LOS compared to patients who received SoC regimens (5.2 days vs 7.2 days, p = 0.013). There was no difference in the rates of infection related readmissions between the dalbavancin and the SoC group (31% vs 31.1%, p = 0.985). Peripherally inserted central catheter line related complications were reported in 17.8% of patients in the SoC group, however the lower incidence of overall adverse events in the dalbavancin group was not significantly different than the SoC group (21.4% vs 36.7%, p = 0.08). Conclusion Dalbavancin administered as a two-dose regimen is a safe and effective option for the treatment of osteomyelitis Disclosures Dustin R. Carr, PharmD, BCPS, BCIDP, AAHIVP, Merck (Speaker's Bureau) Thomas L. Walsh, MD, Accelerate Diagnostics (Other Financial or Material Support, speaking fees)

scholarly journals STEM-01. TARGETING BRAIN METASTASIS-INITIATING CELLS: A PREVENTATIVE APPROACH

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii196-ii196
Author(s):  
Agata Kieliszek ◽  
Chitra Venugopal ◽  
Blessing Bassey-Archibong ◽  
Fred Lam ◽  
Sheila Singh ◽  
...  
Keyword(s):  
At Risk ◽  
Brain Metastasis ◽  
Primary Tumor ◽  
Unmet Need ◽  
Standard Of Care ◽  
Current Standard ◽  
One Year ◽  
Pdx Models

Abstract BACKGROUND The incidence of brain metastases (BM) is tenfold higher than primary brain tumors. BM commonly originate from primary lung, breast, and melanoma tumors with a 90% mortality rate within one year of diagnosis. Current standard of care for BM includes surgical resection with concurrent chemoradiation, but does not extend median survival past 16 months, posing a large unmet need to identify novel therapies against BM. METHODS From a large in-house biobank of patient-derived BM cell lines, the Singh Lab has generated murine orthotopic patient-derived xenograft (PDX) models of lung, breast, and melanoma BM that recapitulate the stages of BM progression as seen in humans. Using these three PDX models, we identified a population of “pre-metastatic” brain metastasis-initiating cells (BMICs) that are newly arrived in the brain but have yet to form detectable tumors. Pre-metastatic BMICs are not detectable in human patients but are important therapeutic targets with the potential to prevent BM in at-risk patients. RESULTS RNA sequencing of pre-metastatic BMICs from all three PDX primary tumor models with subsequent Connectivity Map analysis identified novel compounds that have the potential of killing all three types of BMICs. In particular, we identified two compounds that have selective killing of BMICs in vitro from all three primary tumor cohorts while sparing non-cancerous cells. We further characterized their ability to inhibit the self-renewal and proliferative properties of BMICs. Ongoing in vivo work will investigate the compounds’ preclinical utilities in preventing BM. CONCLUSION Identification of novel small molecules that target BMICs could prevent the formation of BM completely and dramatically improve the prognosis of at-risk cancer patients.

Acute Rejection Following Kidney Transplantation: State-of-the-Art and Future Perspectives

2020 ◽  
Vol 26 (28) ◽  
pp. 3468-3496
Author(s):  
Emilio Rodrigo ◽  
Marcio F. Chedid ◽  
David San Segundo ◽  
Juan C.R. San Millán ◽  
Marcos López-Hoyos
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Rescue Therapy ◽  
Standard Of Care ◽  
Rejection Rate ◽  
New Drugs ◽  
High Dose ◽  
Current Standard ◽  
Antibody Mediated Rejection ◽  
Cellular Rejection

: Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available metaanalyses, we performed a narrative review focused on the basic mechanisms and current and future therapies of acute rejection in kidney transplantation. : According to Kidney Disease/Improving Global Outcomes (KDIGO) guidelines, both clinical and subclinical acute rejection episodes should be treated. Usually, high dose steroids and basal immunosuppression optimization are the first line of therapy in treating acute cellular rejection. Rabbit antithymocytic polyclonal globulins are used as rescue therapy for recurrent or steroid-resistant cellular rejection episodes. Current standard-of-care (SOC) therapy for acute antibody-mediated rejection (AbMR) is the combination of plasma exchange with intravenous immunoglobulin (IVIG). Since a significant rate of AbMR does not respond to SOC, different studies have analyzed the role of new drugs such as Rituximab, Bortezomib, Eculizumab and C1 inhibitors. Lack of randomized controlled trials and heterogenicity among performed studies limit obtaining definite conclusions. Data about new direct and indirect B cell and plasma cell depleting agents, proximal and terminal complement blockers, IL-6/IL-6R pathway inhibitors and antibody removal agents, among other promising drugs, are reviewed.

Sign in / Sign up

Export Citation Format

Share Document