Association between adjuvant radiation treatment and breast cancer-specific mortality among older women with comorbidity burden: A comparative effectiveness analysis of SEER-MHOS.

BACKGROUND: The National Comprehensive Cancer Network suggested that older women with low-risk breast cancer (LRBC; i.e., early-stage, node-negative, and estrogen receptor-positive) could omit adjuvant radiation treatment (RT) after breast-conserving surgery (BCS) if they were treated with hormone therapy. However, the association between RT omission and breast cancer-specific mortality among older women with comorbidity is not fully known. METHODS: 1105 older women (≥65 years) with LRBC in 1998-2012 were queried from the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data resource and were followed up through July 2018. Latent class analysis was performed to identify comorbidity burden classes. A propensity score-based inverse probability of treatment weighting (IPTW) was applied to Cox regression models to obtain subdistribution hazard ratios (HRs) and 95% CI for cancer-specific mortality considering other causes of death as competing risks, overall and separately by comorbidity burden class. RESULTS: Three comorbidity burden (low, moderate, and high) groups were identified. A total of 318 deaths (47 cancer-related) occurred. The IPTW-adjusted Cox regression analysis showed that RT omission was not associated with short-term, 5- and 10-year cancer-specific death (p = 0.202 and p = 0.536, respectively), regardless of comorbidity burden. However, RT omission could increase the risk of long-term cancer-specific death in women with low comorbidity burden (HR = 1.98, 95% CI = 1.17, 3.33), which warrants further study. CONCLUSIONS: Omission of RT after BCS is not associated with an increased risk of cancer-specific death and is deemed a reasonable treatment option for older women with moderate to high comorbidity burden.

Do Hospitals Performing Frequent Neuraxial Anesthesia for Hip and Knee Replacements Have Better Outcomes?

BACKGROUND: Neuraxial anesthesia is increasingly recommended for hip/knee replacements as some studies show improved outcomes on the individual level. With hospital-level studies lacking, we assessed the relationship between hospital-level neuraxial anesthesia utilization and outcomes. METHODS: National data on 808,237 total knee and 371,607 hip replacements were included (Premier Healthcare 2006 to 2014; 550 hospitals). Multivariable associations were measured between hospital-level neuraxial anesthesia volume (subgrouped into quartiles) and outcomes (respiratory/cardiac complications, blood transfusion/intensive care unit need, opioid utilization, and length/cost of hospitalization). Odds ratios (or percent change) and 95% CI are reported. Volume-outcome relationships were additionally assessed by plotting hospital-level neuraxial anesthesia volume against predicted hospital-specific outcomes; trend tests were applied with trendlines' R statistics reported. RESULTS: Annual hospital-specific neuraxial anesthesia volume varied greatly: interquartile range, 3 to 78 for hips and 6 to 163 for knees. Increasing frequency of neuraxial anesthesia was not associated with reliable improvements in any of the study's clinical outcomes. However, significant reductions of up to -14.1% (95% CI, -20.9% to -6.6%) and -15.6% (95% CI, -22.8% to -7.7%) were seen for hospitalization cost in knee and hip replacements, respectively, both in the third quartile of neuraxial volume. This coincided with significant volume effects for hospitalization cost; test for trend P < 0.001 for both procedures, R 0.13 and 0.41 for hip and knee replacements, respectively. CONCLUSIONS: Increased hospital-level use of neuraxial anesthesia is associated with lower hospitalization cost for lower joint replacements. However, additional studies are needed to elucidate all drivers of differences found before considering hospital-level neuraxial anesthesia use as a potential marker of quality.

Trends in Perioperative Practice and Resource Utilization in Patients With Obstructive Sleep Apnea Undergoing Joint Arthroplasty.

BACKGROUND: Emerging evidence associating obstructive sleep apnea (OSA) with adverse perioperative outcomes has recently heightened the level of awareness among perioperative physicians. In particular, estimates projecting the high prevalence of this condition in the surgical population highlight the necessity of the development and adherence to "best clinical practices." In this context, a number of expert panels have generated recommendations in an effort to provide guidance for perioperative decision-making. However, given the paucity of insights into the status of the implementation of recommended practices on a national level, we sought to investigate current utilization, trends, and the penetration of OSA care-related interventions in the perioperative management of patients undergoing lower joint arthroplasties. METHODS: In this population-based analysis, we identified 1,107,438 (Premier Perspective database; 2006-2013) cases of total hip and knee arthroplasties and investigated utilization and temporal trends in the perioperative use of regional anesthetic techniques, blood oxygen saturation monitoring (oximetry), supplemental oxygen administration, positive airway pressure therapy, advanced monitoring environments, and opioid prescription among patients with and without OSA. RESULTS: The utilization of regional anesthetic techniques did not differ by OSA status and overall <25% and 15% received neuraxial anesthesia and peripheral nerve blocks, respectively. Trend analysis showed a significant increase in peripheral nerve block use by >50% and a concurrent decrease in opioid prescription. Interestingly, while the absolute number of patients with OSA receiving perioperative oximetry, supplemental oxygen, and positive airway pressure therapy significantly increased over time, the proportional use significantly decreased by approximately 28%, 36%, and 14%, respectively. A shift from utilization of intensive care to telemetry and stepdown units was seen. CONCLUSIONS: On a population-based level, the implementation of OSA-targeted interventions seems to be limited with some of the current trends virtually in contrast to practice guidelines. Reasons for these findings need to be further elucidated, but observations of a dramatic increase in absolute utilization with a proportional decrease may suggest possible resource constraints as a contributor.

Trends in the Use of Regional Anesthesia: Neuraxial and Peripheral Nerve Blocks.

BACKGROUND: A growing body of evidence indicates that the use of regional anesthesia offers advantages over general anesthesia, not only in terms of reducing complications but also regarding resource utilization and patient satisfaction. Because of the paucity of data on the nationwide adoption of regional anesthesia techniques, we aimed to elucidate trends in the use of neuraxial anesthesia (NA) and peripheral nerve blocks (PNBs) in orthopedic surgeries. METHODS: We extracted data from N = 959,257 (Premier Perspective database; 2006-2013) total hip and knee arthroplasties (THA, TKA) and assessed NA/PNB use by a 2-year period, stratified by demographics and hospital factors. Cochran-Armitage trend tests assessed significance of trends. RESULTS: Comparing 2006-2007 with 2012-2013, NA utilization decreased slightly from 21.7% to 19.7% for THA patients; this was 24.7% to 21.3% for TKA patients (with the main drop between 2012 and 2013). Conversely, PNB utilization increased from 6.5% to 8.7% for THA patients and 10.3% to 20.4% for TKA patients (all P < 0.001). These general trends did not change when stratified by patient demographics, whereas stratification by hospital factors did show differences: the highest NA utilization was seen in rural, nonteaching, and small hospitals, whereas the highest PNB utilization was seen in large and teaching hospitals. CONCLUSIONS: Our findings provide important insight into the dynamics of the adoption of regional anesthetic techniques. Whereas PNB utilization is significantly increasing, overall, NA and PNBs are performed in the minority of cases. With accumulating evidence in favor of regional anesthesia, promoting the use of NA and a further increase in PNB utilization could have far-reaching medical and economic implications.

FDG-PET assessment of rectal cancer response to neoadjuvant chemoradiotherapy is not associated with long-term prognosis: a prospective evaluation.

BACKGROUND: At present there is no defined role for routine FDG-PET in the preoperative evaluation of nonmetastatic rectal cancer. OBJECTIVE: The primary objective of this study was to evaluate the ability of FDG-PET to predict long-term prognosis based on the response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. DESIGN: This was a prospective study. SETTINGS: This study was performed at an academic, tertiary care, comprehensive cancer center. PATIENTS: One hundred twenty-seven patients with locally advanced rectal cancer were enrolled between September 1999 and December 2005. INTERVENTIONS: All patients underwent FDG-PET scans before and after neoadjuvant chemoradiotherapy. MAIN OUTCOME MEASURES: FDG-PET parameters were evaluated by at least 2 study board-certified nuclear medicine physicians, and included mean standard uptake value, maximum standard uptake value, total lesion glycolysis, and visual response score. The main outcome measures were time to recurrence and disease-specific survival. RESULTS: Of 127 patients, 82 (65%) were men, the median age was 60 years (range, 27-82), 110 patients had stage II/III disease, and 17 patients had stage IV disease. Median follow-up among survivors was 77 months (range, 1-115 months). Nine patients had unresectable metastatic disease and were excluded from the time-to-recurrence analysis. At 5 years, 74% (95% CI = 66%-81%) of patients had not had recurrences (locally and/or distantly). The 5-year disease-specific survival was 89% (95% CI = 81%-93%). On univariate analysis, visual response score and time to recurrence came closest to having an association (HR = 0.83, 95% CI = 0.68-1.01, p = 0.06). On multivariate analysis, the visual response score was not significant (p = 0.85). No FDG-PET parameter was associated with disease-specific survival. CONCLUSIONS: Assessment of rectal cancer response to neoadjuvant chemoradiotherapy by FDG-PET provides no prognostic information. Therefore, serial FDG-PET before and after neoadjuvant chemoradiotherapy should not be performed for this purpose.

A phase I trial of sorafenib plus gemcitabine and capecitabine for patients with advanced renal cell carcinoma: New York Cancer Consortium Trial NCI 6981.

OBJECTIVE: To define the safety [dose limiting toxicity (DLT)] and recommended phase II dose of the combination of sorafenib plus gemcitabine and capecitabine for advanced renal cell carcinoma (RCC). METHODS: In this phase I dose-escalation study, cohorts of 3 to 6 patients with metastatic RCC received sorafenib (200 or 400 mg po BID), gemcitabine (750 or 1000 mg/m(2) intravenous on days 1 and 8), and capecitabine (415 or 622 mg/m(2) po BID days 1-14) every 21 days using a standard 3+3 design. RESULTS: Fifteen patients with advanced RCC (93% with clear cell histology and 87% treatment naive) received treatment. The recommended phase II doses for the combination were sorafenib 200 mg/m(2) BID continuously plus gemcitabine 750 mg/m(2) intravenous days 1 and 8 and capecitabine 415 mg/m(2) BID days 1 to 14, every 21 days. Of the 15 patients, 3 developed dose-limiting hand-foot syndrome during the first 2 cycles; 2 additional DLT's were grade 3 mucositis and transaminase elevation. Four of 14 evaluable patients had a partial response by response evaluation criteria in solid tumors (29%; 95% confidence interval (CI): 8, 58%). Median progression-free survival was 7.5 months (95% CI-0, 18.7), and median overall survival has not been reached at a median follow-up of 28.8 months. The median number of treatment cycles given was 7 (range, 2-38+). CONCLUSIONS: The combination of sorafenib plus gemcitabine and capecitabine is tolerable, but requires attenuation of sorafenib and capecitabine dosing because of the overlapping toxicity of hand-foot syndrome. Antitumor activity was observed leading to an ongoing phase II trial.

Tutorial in biostatistics: Analyzing associations between total plasma homocysteine and B vitamins using optimal categorization and segmented regression.

Data analysts consider standard regression models (e.g., generalized linear model) or nonparametric smoothing techniques (e.g., loess or splines) when examining the association between two variables. Before this step, a quantile-based summarization is typically used for exploring the exposure-response relationship. Unfortunately, these exploratory approaches may not be optimal or efficient for guiding the formal analysis in many biological and nutritional data settings. We suggest a recently developed method for selection of cutpoints as a tool of data summary and segmented regression as a modeling approach in the analysis of plasma total homocysteine and related vitamins. These methods are often complementary in discovering the underlying complex pattern of association.

Sequential preoperative fluorodeoxyglucose-positron emission tomography assessment of response to preoperative chemoradiation: a means for determining longterm outcomes of rectal cancer.

BACKGROUND: We have previously demonstrated that fluorodeoxyglucose-positron emission tomography (FDG-PET) can assess extent of pathologic response of primary rectal cancer to preoperative chemoradiation. Our goal was to determine the prognostic significance of FDG-PET assessment of rectal cancer response to preoperative chemoradiation. STUDY DESIGN: Fifteen patients with locally advanced primary rectal cancer (clinically bulky or tethered, or ultrasound evidence of T3-4 disease, N1 disease, or both) deemed eligible for preoperative radiation and 5-FU-based chemotherapy (5,040 cGy to the pelvis and 2 cycles of bolus 5-FU/leucovorin) were prospectively enrolled from May 1997 to September 1998. FDG-PET was performed before and 4 to 5 weeks after completion of preoperative chemoradiation. FDG-PET parameters included maximum standard uptake value (SUV(max)), total lesion glycolysis (TLG), and visual response score. Patients were prospectively followed after operation, and disease status was determined. RESULTS: All patients demonstrated some degree of response to preoperative therapy based on pathologic examination. At a median followup of 42 months (range 23 to 54 months), 11 patients had no evidence of disease and 4 had died of disease. The mean percentage decrease in SUV(max) (DeltaSUV(max)) was 69% for patients free from recurrence and 37% for patients with recurrence (p = 0.004). DeltaSUV(max) >or= 62.5 and deltaTLG >or= 69.5 were the best predictors of no-evidence-of-disease status and freedom from recurrence. Patients with DeltaSUV(max) >or= 62.5 and deltaTLG >or= 69.5 had significantly improved disease-specific and recurrence-free survival (p = 0.08, 0.02 and p = 0.03, 0.01, respectively). CONCLUSIONS: Our results indicate that FDG-PET assessment of locally-advanced rectal cancer response to preoperative chemoradiation may predict longterm outcomes.