Changing practice patterns of adjuvant radiation among elderly women with early stage breast cancer in the United States from 2004 to 2014.

Randomized controlled trials (RCTs) have challenged the need for routine radiation therapy (RT) in women ≥ age 70 with favorable early stage breast cancer (BC) due to modest improvement in local control and no survival benefit. We studied practice patterns in RT among elderly women in the United States. We analyzed data from the National Cancer Database (NCDB) of women ≥age 70 diagnosed with T1 or T2 and N0 invasive BC treated with breast conservation surgery (BCS) between 2004 and 2014. Patients were divided into four groups: (1) no RT, (2) partial breast irradiation (PBI); (3) hypofractionation (HF); and (4) conventional whole breast RT (CWBI). Univariable and multivariable analyses (MVA) were performed to compare characteristics among the four RT groups. A subgroup analysis of women with favorable disease (T1N0 ER + HER2-) was also performed with similar statistical comparisons. Of the 66,126 meeting eligibility, 9,570 (14.5%) had PBI, 16,340 (24.7%) had HF, and 40,117 (60.7%) had CWBI. Only 99 patients (0.15%) had RT omitted. Omission of RT increased marginally from 0.04% in 2004 to 0.24% in 2014. MVA identified older age (OR 1.18, CI 1.08-1.28), more comorbidities (Charlson-Deyo Score of 1) (OR 3.36, CI 1.29-8.72), and no hormone therapy (OR 22.07, CI 5.79-84.07) as more likely to have RT omitted. The use of HF increased from 3.9% to 47.0%, P < .001 with a concomitant decrease in CWBI from 88% to 41%, P < .001. MVA identified older age, treatment location, and omission of chemotherapy as associated with HF. No significant differences from the larger cohort were found among the T1N0 subgroup analysis. Despite RCT evidence, omission of RT was rare in the United States, suggesting that more effective outreach methods to disseminate clinical guideline information may be needed.

Is Age Trumping Genetic Profiling in Clinical Practice? Relationship of Chemotherapy Recommendation and Oncotype DX Recurrence Score in Patients Aged < 50 Years versus ≥ 50 Years, and Trends Over Time.

BACKGROUND: Oncotype DX (oDX) is used to predict recurrence and indicate response to chemotherapy in patients with early-stage breast cancer (BC). We evaluated the relationship between age (< 50 vs. ≥ 50 years), recurrence score (RS), chemotherapy use, and trends of oDX testing over time. METHODS: Using the National Cancer Database, we identified women with T1/T2, N0, estrogen receptor-positive BC from 2009 to 2014. We stratified patients by age (< 50 and ≥ 50 years) and RS (low: < 18; intermediate: 18-30; and high: > 30), and compared demographics, tumor characteristics, and chemotherapy recommendations. Management trends were also assessed. RESULTS: From 2009 to 2014, a total of 377,725 cases met the eligibility criteria for oDX testing; 115,052 (30.5%) patients had oDX, and 60,804 (16.1%) were < 50 years of age. The majority had low RS and T1N0 disease. Patients < 50 years of age were more likely to be recommended chemotherapy than those ≥ 50 years of age, regardless of RS (p ≤ 0.001), and were more likely to ultimately undergo chemotherapy (p < 0.001). When stratified by year, oDX utilization increased. There was a decreasing trend in chemotherapy recommendations in both the low- and intermediate-RS groups for both age groups (all p = 0.001), with no change in the high-RS group (< 50 years: p = 0.52; ≥ 50 years: p = 0.67). Univariate and multivariate analyses demonstrated that patients < 50 years of age and those with a higher RS were more likely to be recommended chemotherapy (p < 0.001). CONCLUSIONS: The testing of oDX in BC has significantly increased since first implemented. Results from additional studies such as TAILORx will clarify the current discordant practice patterns between low oDX RSs and adjuvant chemotherapy recommendations.

Breast-conservation Therapy After Neoadjuvant Chemotherapy Does Not Compromise 10-Year Breast Cancer-specific Mortality.

OBJECTIVES: Neoadjuvant chemotherapy can increase the rate of breast-conserving surgery by downstaging disease in patients with breast cancer. The aim of this study was to determine whether patients who received neoadjuvant chemotherapy have equal survival after breast-conservation therapy compared with mastectomy. MATERIAL AND METHODS: Using the New Jersey State Cancer Registry (NJSCR) patients with a primary breast cancer diagnosed between 1998 and 2003 who underwent neoadjuvant chemotherapy were selected (n=1,468). Of those, only patients who received lumpectomy plus radiation (n=276) or mastectomy without radiation (n=442) were included in the analysis. The main outcome measured included 10-year breast cancer-specific mortality, with 90% of patients with known vital status through the end of 2011. RESULTS: Baseline characteristics did not differ significantly between the breast-conservation and mastectomy without radiation groups except with respect to summary stage and lymph node involvement. After propensity score matching these differences were no longer statistically significant; however, both estrogen and progesterone status achieved statistical significance. The Kaplan-Meier survival curve showed that the breast-conservation group had significantly higher breast cancer-specific survival than the mastectomy group (P=0.0046). After adjusting for the propensity score in the regression model, the breast-conservation group continued to show significantly better survival than the mastectomy group (hazard ratios, 0.46; 95% confidence interval, 0.27-0.78). CONCLUSIONS: This study is consistent with previous research showing that breast-conserving surgery after neoadjuvant chemotherapy does not reduce breast cancer-specific survival. In fact, patients undergoing breast-conservation after neoadjuvant therapy appeared to have better survival than patients undergoing mastectomy without radiation.

Fluid administration and morbidity in transhiatal esophagectomy.

BACKGROUND: Esophagectomy is associated with significant morbidity. Optimizing perioperative fluid administration is one potential strategy to mitigate morbidity. We sought to investigate the relationship of intraoperative fluid (IOF) administration to outcomes in patients undergoing transhiatal esophagectomy with particular attention to malnourished patients, who may be more susceptible to the effects of fluid overload. MATERIAL AND METHODS: Patients who underwent transhiatal esophagectomy from 2000-2013 were identified from a retrospective database. IOF rates (mL/kg/hr) were determined and their relationship to outcomes compared. To examine the impact of malnutrition, we stratified patients based on median preoperative serum albumin and compared outcomes. RESULTS AND DISCUSSION: 211 patients comprised the cohort. 74% of patients underwent esophagectomy for esophageal adenocarcinoma. Linear regression analyses were performed comparing independent perioperative variables to four outcomes variables: length of stay, complications per patient, major complications, and Clavien-Dindo classification. IOF rate was significantly associated with three of four outcomes on univariate analysis. Significantly more patients with a preoperative albumin level ≤3.7 g/dL who received more than the median IOF rate experienced more severe complications. CONCLUSIONS: Increased intraoperative fluid administration is associated with perioperative morbidity in patients undergoing transhiatal esophagectomy. Patients with lower preoperative albumin levels may be particularly sensitive to the effects of volume overload.

A risk model to determine surgical treatment in patients with thyroid nodules with indeterminate cytology.

BACKGROUND: Thyroid nodules are present in 19-67 % of the population and have a 5-10 % risk of malignancy. Fine needle aspiration biopsies are indeterminate in 20-30 % of patients, often necessitating thyroid surgery for diagnosis. We hypothesized that developing a risk model incorporating factors associated with malignancy could help predict the risk of malignancy in patients with indeterminate thyroid nodules. METHODS: We identified 151 patients with a cytologic diagnosis of follicular neoplasm (Bethesda IV) who progressed to surgery. We retrospectively analyzed demographic, clinical, sonographic, and cytological variables in relation to thyroid carcinoma. RESULTS: Of 151 patients, 51 (33.8 %) had a final diagnosis of thyroid carcinoma. Papillary carcinoma was diagnosed in 34 patients (66.7 %), follicular carcinoma in 15 (29.4 %), and Hürthle cell carcinoma in 2 (3.9 %). On univariate analysis, younger age, male gender, tobacco use, larger nodule size, and calcifications on ultrasound, nuclear atypia on cytology, and suspicious frozen section were associated with the presence of malignancy. When determining odds ratios, four factors were most predictive of malignancy: nodule calcification [odds ratio (OR) 6.37, 95 % confidence interval (CI) 1.62-25.1, p < 0.01] and nodule size (OR 1.75, 95 % CI 1.19-2.57, p < 0.01) on ultrasound, nuclear atypia on cytology (OR 4.91, 95 % CI 1.90-12.66, p < 0.01), and tobacco use (OR 4.59, 95 % CI 1.30-16.27, p < 0.02). A multivariable model based on these four factors resulted in a c-statistic of 0.82. CONCLUSIONS: A multivariable model based on calcification, nodule size, nuclear atypia, and tobacco use may predict the risk of thyroid cancer requiring a total thyroidectomy in patients with thyroid nodules of indeterminate cytology.

Physiologic variability at the verge of systemic inflammation: multiscale entropy of heart rate variability is affected by very low doses of endotoxin.

INTRODUCTION: Human injury or infection induces systemic inflammation with characteristic neuroendocrine responses. Fluctuations in autonomic function during inflammation are reflected by beat-to-beat variation in heart rate, termed heart rate variability (HRV). In the present study, we determine threshold doses of endotoxin needed to induce observable changes in markers of systemic inflammation, investigate whether metrics of HRV exhibit a differing threshold dose from other inflammatory markers, and investigate the size of data sets required for meaningful use of multiscale entropy (MSE) analysis of HRV. METHODS: Healthy human volunteers (n = 25) were randomized to receive placebo (normal saline) or endotoxin/lipopolysaccharide (LPS): 0.1, 0.25, 0.5, 1.0, or 2.0 ng/kg administered intravenously. Vital signs were recorded every 30 min for 6 h and then at 9, 12, and 24 h after LPS. Blood samples were drawn at specific time points for cytokine measurements. Heart rate variability analysis was performed using electrocardiogram epochs of 5 min. Multiscale entropy for HRV was calculated for all dose groups to scale factor 40. RESULTS: The lowest significant threshold dose was noted in core temperature at 0.25 ng/kg. Endogenous tumor necrosis factor α and interleukin 6 were significantly responsive at the next dosage level (0.5 ng/kg) along with elevations in circulating leukocytes and heart rate. Responses were exaggerated at higher doses (1 and 2 ng/kg). Time domain and frequency domain HRV metrics similarly suggested a threshold dose, differing from placebo at 1.0 and 2.0 ng/kg, below which no clear pattern in response was evident. By applying repeated-measures analysis of variance across scale factors, a significant decrease in MSE was seen at 1.0 and 2.0 ng/kg by 2 h after exposure to LPS. Although not statistically significant below 1.0 ng/kg, MSE unexpectedly decreased across all groups in an orderly dose-response pattern not seen in the other outcomes. CONCLUSIONS: By using repeated-measures analysis of variance across scale factors, MSE can detect autonomic change after LPS challenge in a group of 25 subjects using electrocardiogram epochs of only 5 min and entropy analysis to scale factor of only 40, potentially facilitating MSE's wider use as a research tool or bedside monitor. Traditional markers of inflammation generally exhibit threshold dose behavior. In contrast, MSE's apparent continuous dose-response pattern, although not statistically verifiable in this study, suggests a potential subclinical harbinger of infectious or other insult. The possible derangement of autonomic complexity prior to or independent of the cytokine surge cannot be ruled out. Future investigation should focus on confirmation of overt inflammation following observed decreases in MSE in a clinical setting.

Outcome-volume relationships and transhiatal esophagectomy: minimizing "failure to rescue".

BACKGROUND: The objective of this study is to describe the system and technical factors that enabled our moderate size transhiatal esophagectomy program to achieve low mortality rates. METHODS: A retrospective chart review was conducted on 200 consecutive patients who underwent transhiatal esophagectomy at Robert Wood Johnson University Hospital. Primary outcomes included operative times, estimated blood loss, frequency and nature of complications, and lengths of stay in the hospital and the intensive care unit. RESULTS: In general, surgical outcomes tended to improve over the course of this study. We identified decreased operative time, intra-operative blood loss, frequency of complications, and lengths of intensive care unit and hospital stay as the program matured. Through coordinated actions of the surgical and anesthesia teams, all intraoperative injuries were responded to in an effective, emergent fashion and all but one patient was saved. This resulted in an inhospital and 30-day mortality rate of only 0.5%. CONCLUSIONS: Our study suggests that a dual attending approach, focus on avoiding "failure to rescue", increased volume, and a surgeon driven commitment to quality improvement may lead to low mortality rates after transhiatal esophagectomy.