Real-world risk assessment and treatment initiation among patients with myelofibrosis at community oncology practices in the United States.
ABSTRACT: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm with a prevalence of 4 to 6 per 100,000 people in the USA. Treatment recommendations are risk-adapted. This study was conducted to evaluate how physicians risk-stratify patients at the time of MF diagnosis, the accuracy of the risk stratification, and its effect on treatment selection. Medical charts were reviewed at US community hematology/oncology practices in the Cardinal Health Oncology Provider Extended Network; patient clinical characteristics, risk stratification, and treatment data were collected. Physician-assigned risk categorizations were compared with data-derived risk categorizations based on the International Prognostic Scoring System, the system recommended at diagnosis. A total of 491 patients diagnosed with MF between 2012 and 2016 (mean [SD] age at diagnosis, 65.4 [11.8] years; 54.8% male, 69.2% with primary MF) were included. Risk categorization was not assigned for 30.1% of patients. Of the patients with a physician-assigned risk categorization (n?=?343), a scoring system was used in 49.9%. Compared with data-derived risk categorizations, 42.9% of physician-assigned risk categorizations were incorrect; 85.0% of incorrect physician-assigned risk categorizations were underestimations. Notably, 38.5% of patients with data-derived intermediate- or high-risk categorizations did not initiate treatment within 120 days of diagnosis. Among patients with data-derived intermediate risk, those with an underestimated physician-assigned risk categorization were significantly less likely to receive treatment within 120 days of diagnosis (51.6% with correct physician-assigned categorization vs 18.5% with underestimated risk categorization; P?=?0.0023). These results highlight the gap in risk assessment and the importance of accurate risk stratification at diagnosis.
Project description:Categorizations of multiracial individuals provide insight into the psychological mechanisms driving social stratification, but few studies have explored the interplay of cognitive and motivational underpinnings of these categorizations. In the present study, we integrated research on racial essentialism (i.e., the belief that race demarcates unobservable and immutable properties) and negativity bias (i.e., the tendency to weigh negative entities more heavily than positive entities) to explain why people might exhibit biases in the categorization of multiracial individuals. As theorized, racial essentialism, both dispositional (Study 1) and experimentally induced (Study 2), led to the categorization of Black-White multiracial individuals as Black, but only among individuals evaluating Black people more negatively than White people. These findings demonstrate how fundamental cognitive and motivational biases interact to influence the categorization of multiracial individuals.
Project description:Mechanical failure (MF) following adult spinal deformity (ASD) surgery is a severe complication and often requires revision surgery. Predicting a patient's risk of MF is difficult, despite several potential risk factors that have been reported. The purpose of this study was to establish risk stratification model for predicting the MF based on demographic, and radiographic data. This is a multicenter retrospective review of the risk stratification for MF and included 321 surgically treated ASD patients (55?±?19?yr, female: 91%). The analyzed variables were recorded for at least 2?yr and included age, gender, BMI, BMD, smoking status, frailty, fusion level, revision surgery, PSO, LIF, previous surgery, spinal alignment, GAP score, Schwab-SRS type, and rod materials. Multivariate logistic regression analyses were performed to identify the independent risk factors for MF. Each risk factor was assigned a value based on its regression coefficient, and the values of all risk factors were summed to obtain the PRISM score (range 0-12). We used an 8:2 ratio to split the data into a training and a testing cohort to establish and validate the model. MF developed in 41% (n?=?104) of the training subjects. Multivariate analysis revealed that BMI, BMD, PT, and frailty were independent risk factors for MF (BMI: OR 1.7 [1.0-2.9], BMD: OR 3.8 [1.9-7.7], PT: OR 2.6 [1.8-3.9], frailty: OR 1.9 [1.1-3.2]). The MF rate increased with and correlated well with the risk grade as shown by ROC curve (AUC of 0.81 [95% CI 0.76-0.86]). The discriminative ability of the score in the testing cohort was also good (AUC of 0.86 ([95% CI 0.77-0.95]). We successfully developed an MF-predicting model from individual baseline parameters. This model can predict a patient's risk of MF and will help surgeons adjust treatment strategies to mitigate the risk of MF.
Project description:Background:Mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) is a rare lymphoma localized in the skin. Due to its indolent nature and similarity to other skin conditions, diagnosis is often delayed or incorrect. Consequently, accurate calculations of incidence and prevalence are difficult to make. The treatment pathway taken by MF-CTCL patients can differ depending upon local healthcare systems, clinical policies and guidelines. Aims:This study aims to (1) provide an estimate for the prevalence of treated MF-CTCL patients in Spain, (2) describe the Spanish patient treatment pathways for MF-CTCL, including quantification of the distribution of patients between primary, secondary and tertiary care institutions, and (3) investigate and quantify the treatment preferences of physicians. Methodology:This study employed primary market research methodologies to facilitate the collection of patient numbers and treatment practices from healthcare professionals (HCPs) and patients. Limitations:Poor diagnosis of MF-CTCL may mean that actual prevalence levels in the broader population are higher than those estimated by this analysis of treated patients. This study was reliant upon accurate reporting by HCPs of patient numbers and their personal treatment practices. The rarity of the condition means the patient sample size is relatively small and limits possible accuracy of the quantitative analyses of patient-derived data, although this is supplemented by HCP-derived data in the analysis. Findings:Around 75% of MF-CTCL patients in Spain report that the initial diagnosis by their general practitioner is incorrect. This is usually due to underestimation of severity or type of skin disease. Once they have been correctly diagnosed (usually by a dermatologist) in secondary care, the management of MF-CTCL is led by dermatologists. In 39% of patients, shared care teams are also involved in patient management. Following diagnosis, the majority of patient management is conducted by secondary or tertiary care centers. Conclusions:Incidence rates have increased in recent years, and possible reasons for this include improving levels of diagnosis. Survival in MF-CTCL has also increased over the last few decades. This trend appears to be reflected in the prevalence reported in this study, which is higher than suggested by some other estimates. However, it is still likely that there are further undiagnosed MF-CTCL patients in Spain due to the challenges of diagnosis at the primary care level.
Project description:Medulloblastoma (MB) is the most common pediatric brain tumor and is an aggressive neoplasia arising in the cerebellum. MB includes four major histological subsets commonly subdivided in: classic, desmoplastic, anaplastic or large-cell, and nodular. The current patients risk stratification is based on the age at diagnosis (> or < 3 years at diagnosis), the extent of residual tumor mass post-operative, and disease dissemination. An average risk is assigned to patients older than 3 years of age with minimal or no tumor residual. These patients are more than 60% of overall MBs and have an overall survival between 50-70% at 5 years. It is widely accepted that tumor aggressiveness and progression depend on genetic abnormalities. We performed the genome-wide study, focused on classic MB belonging to pediatric patients at standard risk. We analyzed 31 MB samples using high resolution oligonucleotide Human Genome CGH 244K (Agilent Technologies). The present study may help to identify novel molecular prognostic markers useful to refining current criteria of patients´ relapse risk estimation in this subgroup of patients. We analyzed 31 samples of classic medulloblastoma from patients older than 3 years of age at diagnosis
Project description:Pheochromocytoma and paraganglioma (PPGL) can be divided into at least four molecular subgroups. Whether such categorizations are independent factors for prognosis or metastatic disease is unknown. We performed a systematic review and individual patient meta-analysis aiming to estimate if driver mutation status can predict metastatic disease and survival. Driver mutations were used to categorize patients according to three different molecular systems: two subgroups (SDHB mutated or wild type), three subgroups (pseudohypoxia, kinase signaling or Wnt/unknown) and four subgroups (tricarboxylic acid cycle, VHL/EPAS1, kinase signaling or Wnt/unknown). Twenty-one studies and 703 patients were analyzed. Multivariate models for association with metastasis showed correlation with SDHB mutation (OR 5.68 (95% CI 1.79-18.06)) as well as norepinephrine (OR 3.01 (95% CI 1.02-8.79)) and dopamine (OR 6.39 (95% CI 1.62-25.24)) but not to PPGL location. Other molecular systems were not associated with metastasis. In multivariate models for association with survival, age (HR 1.04 (95% CI 1.02-1.06)) and metastases (HR 6.13 (95% CI 2.86-13.13)) but neither paraganglioma nor SDHB mutation remained significant. Other molecular subgroups did not correlate with survival. We conclude that molecular categorization accordingly to SDHB provided independent information on the risk of metastasis. Driver mutations status did not correlate independently with survival. These data may ultimately be used to guide current and future risk stratification of PPGL.
Project description:Medulloblastoma (MB) is the most common pediatric brain tumor and is an aggressive neoplasia arising in the cerebellum. MB includes four major histological subsets commonly subdivided in: classic, desmoplastic, anaplastic or large-cell, and nodular. The current patients risk stratification is based on the age at diagnosis (> or < 3 years at diagnosis), the extent of residual tumor mass post-operative, and disease dissemination. An average risk is assigned to patients older than 3 years of age with minimal or no tumor residual. These patients are more than 60% of overall MBs and have an overall survival between 50-70% at 5 years. It is widely accepted that tumor aggressiveness and progression depend on genetic abnormalities. We performed the genome-wide study, focused on classic MB belonging to pediatric patients at standard risk. We analyzed 31 MB samples using high resolution oligonucleotide Human Genome CGH 244K (Agilent Technologies). The present study may help to identify novel molecular prognostic markers useful to refining current criteria of patients´ relapse risk estimation in this subgroup of patients. Overall design: We analyzed 31 samples of classic medulloblastoma from patients older than 3 years of age at diagnosis
Project description:Purpose:The aim of our study was to evaluate the clinical characteristics of myelodysplastic syndrome (MDS) patients with concomitant mild-to-moderate myelofibrosis (MF), and to assess its independent prognostic role in MDS patients diagnosed by World Health Organization 2016 classification (WHO2016C) with long-term follow-up. Patients and Methods:A total of 157 patients with primary MDS associated with or without MF were examined retrospectively with long-term follow-up. MF graded as MF-1/MF-2 was defined as "mild/moderate". Cytogenetics testing and fluorescence in situ hybridization (FISH) were also conducted in all MDS patients. Results:Thirty-four (21.7%) of 157 MDS patients had MF. Also, 24 (15.3%) MDS patients based on WHO2016 criteria were defined as MF-1 and 10 (6.4%) as MF-2. MDS patients with MF-1/2 had a higher prevalence of death (p=0.002), leukemic progression (p=0.013), O blood type (p=0.039) as well as less hypercellular proliferation (p<0.001) and less supportive treatment (p=0.003) compared with those without mild/moderate MF. Cytogenetics testing did not show a significant difference between MDS patients with and without MF. Multivariate analyses showed that MF (mild/moderate), a monosomal karyotype (MK) and % bone-marrow blasts were independently associated with shorter overall survival (OS) and progression-free survival (PFS). Age was an independent indicator of the adverse OS of MDS patients. Compared with those without MF, MDS patients with mild/moderate MF were significantly associated with worse OS and PFS in MK-negative subgroups and relatively low-risk Revised International Prognostic Scoring System for Myelodysplastic Syndromes (IPSS-R) stratification in long-term follow-up. Conclusion:Mild/moderate myelofibrosis and monosomal karyotype are independent indicators of a poor clinical outcome in MDS patients. In long-term follow-up, MDS with mild/moderate MF can be a prognostic marker for MDS patients with a specific MK stratification and IPSS-R stratification.
Project description:Social categorization is often thought to be based on facial features and immune to visual context. Moreover, East Asians have been argued to attend to context more than Westerners. American and Chinese participants were presented with faces varying along a White-Asian morph continuum either in American, neutral, or Chinese contexts. American contexts made White categorizations more likely, and Chinese contexts made Asian categorizations more likely. Further, the compatibility between facial and contextual cues influenced the directness of participants' hand trajectories en route to selecting a category response. Even when an ultimate response was not biased by context, the trajectory was nevertheless partially attracted to the category response associated with the context. Importantly, such partial attraction effects in hand trajectories revealed that the influence of context began earlier in time for Chinese relative to American participants. Together, the results show that context systematically influences social categorization, sometimes altering categorization responses and other times only temporarily altering the process. Further, the timing of contextual influences differs by culture. The findings highlight the role of contextual and cultural factors in social categorization.
Project description:Detection of specific chromosomal abnormalities by FISH and metaphase cytogenetics allows risk stratification in multiple myeloma (MM); however, gene expression profiling (GEP) based signatures may enable more specific risk categorization. We examined the utility of two GEP-based risk stratification systems among patients undergoing initial therapy with lenalidomide in the context of a phase 3 trial. The E4A03 clinical trial randomized patients with previously untreated MM to lenalidomide and either standard-dose dexamethasone. Baseline bone marrow samples were obtained from consenting patients. The marrow aspirates were subjected to a fully automated ROBOSEP cell separation system that utilizes immunomagnetic technology to positively select for CD 138+ cells. The purity of the sorting was confirmed by 3-color immunofluorescent slide based assessment on the sorted cells. The plasma cell gene expression proﬁles were analyzed using U133 Plus 2.0 array. All samples were run individually with no pooling. The GEP-70 signature was determined as previously described, using log2 transformed raw MAS 5.0 signals. The GEP15 classification was performed as previously described, with the patients in highest quartile for the risk score being considered as high risk.