Patients with relapsed and refractory multiple myeloma have a poor prognosis. The mitogen-activated protein kinase (MAPK) pathway has been implicated in the pathogenesis of multiple myeloma. Several mutations in this pathway can lead to its constitutive activation leading to oncogenesis. One such mutation is BRAFV600E which is a therapeutic target in the treatment of melanoma, lung cancer, colon cancer, thyroid cancer, and hairy cell leukemia. BRAFV600E-directed therapy currently does not have approval in multiple myeloma. It has been proposed that this mutation leads to proteasome inhibitor resistance. About 4-10% of multiple myeloma cases harbor the BRAFV600E mutation. Herein, we report a case of a patient with relapsed and refractory multiple myeloma who had a progression-free survival (PFS) of 8.5 months on BRAF-targeted therapy.
e18506 Background: Studies on outcomes of AYAs with AML and APL are limited. We sought to compare outcomes of AYAs and pediatric patients (pts) with AML (pAML) and APL (pAPL) using the Surveillance Epidemiology and End Results (SEER) registry. Methods: We utilized SEER-18 registry to identify pediatric (0-18 years) and AYA (age 19-30 years) pts with AML and APL. Survival statistics were computed using Kaplan-Meier method and compared using Z-test for population proportions. Early mortality rate (EMR), defined as mortality within 1 month of diagnosis, was used as a surrogate for treatment related mortality. Kaplan Meier (KM) survival curves were plotted and compared using log-rank test. Multivariate analysis was done using logistic regression and Cox proportional hazard regression model. All p-values were two-sided using significance level of 0.05. Results: 6343 AML pts were identified, and 44.7% were AYAs. Most pts were categorized as AML, not otherwise specified (56%). EMR was lower in pAML as compared to AYAs (6.2% vs 9.2%; p < 0.01). 1-year overall survival (OS) (70.3% vs 62.1%; p < 0.01) and 5-year OS was higher in pediatric pts versus AYAs (48.2% vs 36.4%; p < 0.01). KM plot showed worse OS for AYAs versus pAML. 920 APL pts were identified, and 59.5% were AYAs. EMR in pAPL compared to AYAs was 11.4% vs 14.1% (p = 0.23). 1-year OS (83.8% vs 81.2%; p = 0.31) and 5-year OS rates were not significantly different (68.2% vs 73.1%; p = 0.11). KM plot also showed similar OS for AYAs and pAPL. EMR for both AYAs and pAPL pts (11.4% and 14.1%) was higher than AYAs and pAML (6.2% and 9.2%). In contrast, OS for AYAs and pAPL pts (5-year OS 68.2% and 73.1%) was better than AYAs and pAML (5-year OS 48.2% and 36.4%). Conclusions: Our population based analysis showed AYAs with AML have worse EMR and OS compared to pAML. In contrast, AYAs and pAPL pts, managed with similar treatment protocols have similar outcomes. This observation supports that standardizing treatment protocols for AYAs with AML similar to pediatric pts may reduce EMR and OS to the rates seen in pAML pts. To our knowledge this is the first study to compare survival outcomes for pediatric and AYA pts with AML and APL.
Primary central nervous system (CNS) tumors and brain metastases (BMs) are major causes of morbidity and mortality, accompanied by low survival rates. Efforts to early discovery of CNS malignancies are critical. However, to date, there are no biomarkers approved for detection of cancer activity in the brain. Blood levels of neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp), show promise as biomarkers for brain injury in previous studies. Therefore, we performed a cross-sectional study to investigate correlations of those biomarkers with CNS activity of gliomas and BMs.Serum samples of 36 participants of a single centered institution were tested for NfL, GFAp and tau with Simoa immunoassay, and correlated with clinical and radiological data.NfL and GFAp levels were significantly associated with the state of intracranial disease (analysis of variance (ANOVA), PsNfL = 0.03; ANOVA, PGFAp = 0.03). Although statistically significant (P = 0.04), differences in concentrations were not clinically meaningful for tau levels. Serum NfL (sNfL) and GFAp concentrations were higher in the group of patients with CNS tumors with disease in progression versus CNS with stable disease (P = 0.03 and P = 0.01, respectively). In addition, sNfL were higher in patients with metastatic solid tumors with known BMs than in those with metastatic tumors with no BM (P = 0.0004).sNfL and GFAp both apparently vary closely with presence and activity of gliomas and BMs. Further studies in larger populations are needed to expand these findings.
The timing of umbilical cord clamping is a pivotal decision in neonatal care, especially for preterm babies. Recent discussions have pivoted around the merits and drawbacks of Delayed Cord Clamping (DCC) compared to Immediate Cord Clamping (ICC). This study aimed to assess and contrast the implications of DCC versus ICC on clinical, respiratory, developmental, and maternal outcomes among preterm neonates. A multicentric, forward-looking, cross-sectional investigation was executed. The study encompassed 350 preterm neonates from various centers. They were categorically split: 175 underwent DCC, while the other 175 experienced ICC. Diverse outcomes, spanning clinical to maternal, were meticulously evaluated. DCC neonates demonstrated elevated early post-birth hemoglobin and hematocrit measurements. The DCC group reported reduced polycythemia occurrences, diminished transfusion necessities, and lesser demands for cardiovascular interventions. Regarding respiratory metrics, the DCC faction showed a decreased incidence of RDS. Neurodevelopmental indicators, such as cognitive and motor capabilities, were more pronounced in the DCC segment. The DCC group manifested reduced neonatal mortality rates and fewer sepsis cases. Maternally, post-delivery hemorrhage was comparable between groups, yet the DCC set displayed heightened satisfaction and a more pronounced initiation and continuity in breastfeeding. The evidence suggests that DCC may present multiple benefits over ICC for preterm neonates in terms of health and developmental outcomes. This underscores the potential of DCC as an integral component of best practices in neonatal care for premature babies.
Introduction: While the morbidity and mortality attributable to gliomas and brain metastases is significant, there are currently no approved biomarkers for detecting and monitoring intracranial disease and imaging remains the primary modality. Blood levels of the neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp) show promise as biomarkers for brain injury. We therefore hypothesized that these biomarkers would correlate with CNS activity of gliomas and brain metastases.Methods: Serum concentrtaions of NfL, tau and GFAp were measured using the ultrasensitive single molecule array (Simoa) technology (Quanterix, Lexington, MA). Levels of the three proteins were then correlated with status of gliomas and brain metastases in the patients. Statistical analysis was performed using GraphPad Prism7 and all p-values were 2-tailed with an accepted 2-sided alpha level of 0.05 as statistically significant.Results: 36 patients were enrolled with varying malignancies. Both serum NfL and GFAp levels were significantly associated with the state of intracranial disease (ANOVA psNfL= 0.0307; ANOVA pGFAp=0.0348). In contrast, serum tau levels were discordant with brain involvement with cancer (ANOVA pTau= 0.1453).Conclusion: Serum NfL and GFAp both apparently vary closely with presence and activity of gliomas and brain metastases. Our studies are among the first to identify possible candidate serum biomarkers for screening and monitoring cancer patients for CNS involvement with malignancy. Further studies in larger populations are needed to expand these findings.Citation Format: Jason Porter, Adriana Hepner, Manjari Pandey, Philippe Prouet, Felicia Hare, Syed S. Nasir, Madison Boles, Henrik Zetterberg, Kaj Blennow, Michael Martin. Serum neurofilament light (NfL), glial fibrillary acidic protein (GFAp) and tau protein are possible serum biomarkers for activity of brain metastases and gliomas [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 1352.
e17586 Background: Large data bases have been analyzed to evaluate the number of cancer patients who die in intensive care (ICU) settings. Little information regarding details of care of these (retrospectively) futile efforts have been explored. Methods: We studied 421 charts of patients who died in the ICU at a university affiliated Veteran’s Affairs Medical Center between 10/2005 and 10/2010. We identified 52 patients with advanced, incurable cancer and performed an in depth review of their records. Results: The mean age was 66 with 9 over 80. Mean duration of cancer awareness was 7.3 months with 14 patients aware of their diagnosis < 1 month. Mean survival in ICU was 4.3 days with 25 living one day or less. 26 patients were supported by ventilators. Only 16 patients had documented discussions regarding treatment preferences or advanced directives prior to admission. 29 did have treatment preference discussions in hospital prior to ICU admission in an urgent situation. 6 patients were directly admitted from the emergency center to the ICU and 6 were post procedure ICU admissions. 38 had expected durations of life prior to ICU of 6 months or less. Only 3 had palliative care consults prior to ICU admission. Conclusions: Decision making behind futile ICU admissions for cancer patients is quite variable and complex. A large percentage of our patients make these decisions on an urgent basis and often within a few weeks of their diagnosis. This data suggests that treatment preference decisions, including ICU admissions, should be made in out-patient settings, divorced from urgent decision making. From this data we have developed an EMR template, designed for easily obtainable out-patient treatment preference discussions, which can be accessed by in-patient providers. Outcome measures utilizing this template are ongoing and preliminary findings will be available.
Abstract Introduction: While the morbidity and mortality attributable to gliomas and brain metastases is significant, there are currently no approved biomarkers for detecting and monitoring intracranial disease and imaging remains the primary modality. Blood levels of the neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp) show promise as biomarkers for brain injury. We therefore hypothesized that these biomarkers would correlate with CNS activity of gliomas and brain metastases. Methods: Serum concentrtaions of NfL, tau and GFAp were measured using the ultrasensitive single molecule array (Simoa) technology (Quanterix, Lexington, MA). Levels of the three proteins were then correlated with status of gliomas and brain metastases in the patients. Statistical analysis was performed using GraphPad Prism7 and all p-values were 2-tailed with an accepted 2-sided alpha level of 0.05 as statistically significant. Results: 36 patients were enrolled with varying malignancies. Both serum NfL and GFAp levels were significantly associated with the state of intracranial disease (ANOVA psNfL= 0.0307; ANOVA pGFAp=0.0348). In contrast, serum tau levels were discordant with brain involvement with cancer (ANOVA pTau= 0.1453). Conclusion: Serum NfL and GFAp both apparently vary closely with presence and activity of gliomas and brain metastases. Our studies are among the first to identify possible candidate serum biomarkers for screening and monitoring cancer patients for CNS involvement with malignancy. Further studies in larger populations are needed to expand these findings. Citation Format: Jason Porter, Adriana Hepner, Manjari Pandey, Philippe Prouet, Felicia Hare, Syed S. Nasir, Madison Boles, Henrik Zetterberg, Kaj Blennow, Michael Martin. Serum neurofilament light (NfL), glial fibrillary acidic protein (GFAp) and tau protein are possible serum biomarkers for activity of brain metastases and gliomas [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 1352.
106 Background: Often end of life discussions are either not held in a timely manner or remain poorly communicated when outpatients are transferred to hospital care. This leads to unwarranted and costly interventions. Methods: In an academic oncology clinic we developed an electronic medical record (EMR) template that listed important information for management decisions, including life expectancy, goals of management and specific patient treatment preferences (ventilator support, tube feedings, transfusions, do-not-resuscitate (DNR) wishes, etc.). The completed note was placed in an easily retrievable location in patients’ electronic charts. Clinic charts were reviewed one week ahead of visits to identify patients who were within the last year of life and a pop up reminder for the treating physician was placed in the EMR. The physicians who admitted our patients to the hospital were educated on utilization of the template notice. We compared the percentage of patients with advanced directives or treatment preference notes before the intervention with the percentage 1½ years after the intervention was begun. We utilized a cross-sectional, self-administered survey to compare in-patient physician responses before and after implementation of the intervention to evaluate the in-hospital utility of the intervention. Results: Easily accessible treatment preference or advanced directive discussions with patients in their last year of life increased from 32% to 55% (p =0.004) with the intervention. Results of the survey also showed improved understanding of patient’s wishes for DNR status (26.9% vs 52.6%, p = 0.08) among admitting physicians. Conclusions: The development of an easily utilized EMR template to record the treatment preferences of patients near the end of life, with an EMR accountability instrument, improved both documentation of discussion and physician understanding of patient treatment preferences when patients were transferred from outpatient to inpatient care. We hypothesize that this intervention will lead to a decline in costly and unwanted interventions for patients near the end of life, and plan to test this hypothesis with further outcomes measures.
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