Disparity in Utilization of Multiagent Therapy for Acute Promyelocytic Leukemia in the United States

BackgroundDespite high rate of cure in acute promyelocytic leukemia (APL) in clinical trials, outcomes in real-world practice are dismal. We utilized National Cancer Database (NCDB) to explore utilization of multiagent therapy in APL and identify any disparities in treatment in real-world practices.Patients and MethodsNCDB categorizes use of systemic chemotherapy into single agent versus multiagent therapy. Some patients received hormonal therapy, immunotherapy, and unknown therapy; details of these treatments could not be ascertained. We therefore used multiple logistic regression analysis to evaluate effects of covariates on the probability of multiagent therapy use in 6678 patients.ResultsCompared to patients >60 years, patients aged 0 to 18 years (hazard ratio[HR] 3.2, 95% confidence interval [CI] 1.8-5.5, P< .0001), 19 to 40 years (HR 1.6, 95% CI 1.03-2.54, P= .03), and 41 to 60 years (HR 1.6, 95% CI 1.3-1.9, P< .0001) were more likely to receive multiagent therapy. Patients with Charlson comorbidity index (CCI) of 0 (HR 1.6, 95% CI 1.2-2.3, P= .001) and CCI of 1 (HR 1.4, 95% CI 1.0-1.9, P= .04) had a higher likelihood of receiving multiagent therapy than patients with CCI ≥ 3. Patients treated at academic cancer centers, compared to those treated at community cancer center (HR 0.5, 95% CI 0.3-0.7, P= .001), comprehensive community cancer center (HR 0.7, 95% CI 0.6-0.8, P< .0001), and integrated network cancer center (HR 0.8, 95% CI 0.6-0.9, P= .02) were more likely to be treated with multiagent therapy. Compared to the patients with private insurance, those with Medicaid had increased likelihood (HR 1.2, 95% CI 1.0-1.4, P= .04) whereas uninsured patients had a lower likelihood of receiving multiagent therapy (HR 0.6, 95% CI 0.5-0.8, P= .0005).ConclusionTo our knowledge, this study is the first and the largest scale analysis of treatment practices in APL in real-world practices. Our findings highlight significant disparities in treatment of APL based on age, insurance, and health-system factors.     

Risk as a pattern over time: Delineation of time-dependent risk factors in biological,psychological, and social variables in cancer patients

Background

Survival in cancer patients is associated with a multitude of biological, social, and psychological factors. Although it is well established that all these factors add to overall mortality, it is not well understood how the predictive power of these parameters changes in a comprehensive model and over time.

Methods

Patients who attended the authors’ outpatient clinic were invited to participate. The authors followed 5180 mixed cancer patients (51.1% female; mean age, 59.1 years [SD = 13.8]) for up to 16 years and analyzed biological (age, sex, cancer site, anemia), psychological (anxiety, depression), and social variables (marital status, education, employment status) potentially predicting overall survival in a Cox proportional hazards model.

Results

The median survival time for the entire sample was 4.3 years (95% confidence interval, 4.0–4.7). The overall survival probabilities for 1 and 10 years were 76.8% and 38.0%, respectively. Following an empirical approach, the authors split the time interval into five periods: acute, subacute, short-term, medium-term, and long-term. A complex pattern of variables predicted overall survival differently in the five periods. Biological parameters were important throughout most of the time, social parameters were either time-independent predictors or tended to be more important in the longer term. Of the psychological parameters, only depression was a significant predictor and lost its predictive power in the long-term.

Conclusions

The findings of this study allow the development of comprehensive patient-specific models of risk and resilience factors addressing biopsychosocial needs of cancer patients, paving the way for a personalized treatment plan that goes beyond biomedical cancer care.     

A SEER analysis of survival and prognostic factors in merkel cell carcinoma of the head and neck region

While Merkel cell carcinoma (MCC) of the head and neck is highly malignant, it remains poorly characterized due to its rarity. The purpose of this study was to examine prognostic factors for overall survival (OS) and disease-specific survival (DSS) in patients with MCC of the head and neck region. The Surveillance, Epidemiology and End Results registry was reviewed for patients diagnosed between 1984 and 2016 with histologically confirmed, primary MCC of the head and neck region. A total of 2818 patients met the inclusion criteria, with a median age at diagnosis of 77 years. At five and 10 years, respectively, the OS was 42.4% and 25.1% and the DSS was 67.9% and 64.1%. Multivariate Cox analysis indicated that predictors of decreased DSS included age at diagnosis ≥75 years, white race, increasing tumor spread, lymph node involvement and either the lip or the scalp/neck as a primary site. When adjusting for the aforementioned factors, tumor depth was not found to be a prognostic factor for DSS. We anticipate these results will help clinicians to counsel patients regarding expectations and potential prognosis.     

Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma

Background

Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.

Methods

Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.

Results

Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.

Conclusions

Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS.     

Survival effects of time to surgery for Stage I lung cancer: A population-based study

ObjectivesTo examine the impact of time to surgery (TTS) on survival among patients with stage I non-small cell lung cancer (NSCLC).MethodsAll patients in the Canadian province of Ontario with stage I NSCLC from 2007 to 2017 were included. A logistic regression identified the predictors of TTS and a flexible parametric model estimated survival rates based on TTS.ResultsOver the study period, 6428 patients with stage I NSCLC undergoing surgical resection were identified, of which 62.5% had TTS >28 days. Less than half these patients (40.8%) underwent open resection, with 19.3% undergoing open sublobar and 21.5% undergoing open lobectomy. Adenocarcinoma and squamous cell carcinoma tumors accounted for 33.3% and 22.0% of cases, respectively. The majority (85.6%) of patients lived in urban areas within 50 km of a regional cancer center (76.9%). Variables that predicted TTS >28 days include age and extent of resection. After adjustment for VATS vs. open resection, age, sex, frailty, year of diagnosis, histology of tumor, and extent of resection, the hazard ratio for TTS >28 days was 1.26 (95%CI:1.13–1.40), indicating a 26% increased risk of all-cause mortality (p < 0.0001). The highest 5-year survival was observed for patients with stage I disease undergoing resection within 28 days.ConclusionsThe present study found age and extent of resection to be associated with increased TTS. Importantly, patients with TTS >28 days had reduced long-term survival.     

婚姻状态对原发性中枢神经系统淋巴瘤患者预后的影响：一项倾向性评分匹配研究

背景 原发性中枢神经系统淋巴瘤（PCNSL）的预后较差，明确其预后危险因素是改善其预后的关键。生物-心理-社会医学模式提示社会心理因素的重要性。婚姻是重要的社会心理因素之一，但婚姻状态对PNSCL患者预后的影响尚不明确。 目的 探究婚姻状态对PCNSL患者总生存（OS）和癌因生存（CSS）的影响。 方法 于2020年，提取2000—2016年美国"监测、流行病学和结果"数据库的3 993例PCNSL患者的病例资料，包括社会人口学资料（婚姻状态、确诊年龄、种族、性别和确诊年份）、临床病理资料（病理类型、肿瘤位置）、治疗资料（手术、放疗和化疗）及结局资料（生存信息和随访时间）。依据婚姻状态将患者分为已婚和非已婚两组，其中非已婚包括单身、离异和丧偶。采用倾向性评分匹配均衡基线资料，采用Kaplan-Meier分析（Log-rank检验）、Cox回归评估婚姻状态对患者OS和CSS的影响。 结果 倾向性评分匹配后，已婚组和非已婚组患者基线资料比较，差异均无统计学意义（P>0.05）。将患者按婚姻状态分为已婚和非已婚组：Log-rank检验结果显示，与已婚患者相比，非已婚患者的OS和CSS更差（P<0.05）；倾向性评分匹配后，校正确诊年龄、种族、性别、确诊年份、病理类型、肿瘤位置、手术、放疗和化疗因素后，多因素Cox回归分析结果显示，非已婚患者的OS风险是已婚患者的1.24倍〔95%CI（1.14，1.36），P<0.001〕，非已婚患者的CSS风险是已婚患者的1.22倍〔95%CI（1.11，1.33），P<0.001〕。将患者按婚姻状态分为已婚、单身、离异、丧偶组：Log-rank检验结果显示，与已婚患者相比，丧偶患者的OS和CSS预后更差（P<0.05）；校正确诊年龄、种族、性别、确诊年份、病理类型、肿瘤位置、手术、放疗和化疗因素后，多因素Cox回归结果显示，单身患者OS和CSS风险分别是已婚患者的1.14倍〔95%CI（1.03，1.27），P=0.013〕和1.15倍〔95%CI（1.03，1.29），P=0.012〕，离异患者OS和CSS风险分别是已婚患者的1.23倍〔95%CI（1.07，1.41），P=0.004〕和1.22倍〔95%CI（1.05，1.41），P=0.009〕，丧偶患者OS和CSS风险分别是已婚患者的1.37倍〔95%CI（1.21，1.54），P<0.001〕和1.28倍〔95%CI（1.12，1.46），P=0.013〕。 结论 婚姻状态影响PCNSL患者OS和CSS，与已婚相比，单身、离异和丧偶患者的预后更差，这提示在临床管理和决策中，除了传统的肿瘤生物学特征，还应关注婚姻状态对PCNSL患者预后的影响。     

Outcomes of coronary artery bypass grafting in patients with heart failure with a midrange ejection fraction

BackgroundCoronary artery bypass grafting (CABG) improves survival in patients with heart failure and severely reduced left ventricular systolic function (LVEF). Limited data exist regarding adverse cardiovascular event rates after CABG in patients with heart failure with midrange ejection fraction (HFmrEF; LVEF > 40% and < 55%).MethodsWe analyzed data on isolated CABG patients from the Veterans Affairs national database (2010-2019). We stratified patients into control (normal LVEF and no heart failure), HFmrEF, and heart failure with reduced LVEF (HFrEF) groups. We compared all-cause mortality and heart failure hospitalization rates between groups with a Cox model and recurrent events analysis, respectively.ResultsIn 6533 veterans, HFmrEF and HFrEF was present in 1715 (26.3%) and 566 (8.6%) respectively; the control group had 4252 (65.1%) patients. HFrEF patients were more likely to have diabetes mellitus (59%), insulin therapy (36%), and previous myocardial infarction (31%). Anemia was more prevalent in patients with HFrEF (49%) as was a lower serum albumin (mean, 3.6 mg/dL). Compared with the control group, a higher risk of death was observed in the HFmrEF (hazard ratio [HR], 1.3 [1.2-1.5)] and HFrEF (HR, 1.5 [1.2-1.7]) groups. HFmrEF patients had the higher risk of myocardial infarction (subdistribution HR, 1.2 [1-1.6]; P = .04). Risk of heart failure hospitalization was higher in patients with HFmrEF (HR, 4.1 [3.5-4.7]) and patients with HFrEF (HR, 7.2 [6.2-8.5]).ConclusionsHeart failure with midrange ejection fraction negatively affects survival after CABG. These patients also experience higher rates myocardial infarction and heart failure hospitalization.