Publications by authors named "Karen J Ruth"

24 Publications

  • Page 1 of 1

Changes in Burnout Among Oncology Physician Assistants Between 2015 and 2019.

JCO Oncol Pract 2021 Jul 22:OP2100051. Epub 2021 Jul 22.

Fox Chase Cancer Center, Philadelphia, PA.

Purpose: Burnout has significant implications for the individual provider, the oncology workforce, and the quality of care for patients with cancer. The primary aim of this study was to explore temporal changes in burnout among physician assistants (PAs) in oncology in 2019 compared with 2015.

Methods: Oncology PAs were surveyed to assess for burnout using the Maslach Burnout Inventory according to the same cross-sectional design of the study performed in 2015. Comparison between oncology PAs in 2015 and 2019 in the prevalence of burnout and personal and professional characteristics was performed.

Results: Two hundred thirty-four participants completed the full-length survey. The participants in 2015 and 2019 were similar in age (41.8 40.3 years), sex (88.8% 86.3% female), number of years as a PA in oncology (9.6 10), and percentage involved in academic practice (55.2% 59.2%). There was a significant increase in burnout in 2019 compared with 2015 with 48.7% of PAs reporting at least one symptom of burnout compared with 34.8% (odds ratio for burnout, 2019 2015 = 1.92 [95% CI, 1.40 to 2.65], < 0.001). The odds of burnout remained higher in 2019 compared with 2015 when adjusted for age, sex, relationship status, practice setting, subspecialty, practice type, and hours worked. Factors associated with burnout in both 2015 and 2019 include the percentage of time spent on patient care, collaborative physician relationship, number of hours worked, and satisfaction with compensation. No new factors associated with burnout emerged in 2019 that were not identified in 2015.

Conclusion: The rate of burnout of oncology PAs has significantly increased. Burnout in oncology PAs is multifactorial, and the increase cannot be easily explained. Additional research is needed to better define the drivers of PA burnout.
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July 2021

Breast Reconstruction in Inflammatory Breast Cancer: An Analysis of Predictors, Trends, and Survival from the National Cancer Database.

Plast Reconstr Surg Glob Open 2021 Apr 15;9(4):e3528. Epub 2021 Apr 15.

Department of Surgery, Einstein Healthcare Network, Philadelphia, Pa.

Introduction: Survival for women diagnosed with inflammatory breast cancer (IBC) has improved with advances in multimodal therapy. This study was performed to evaluate trends, predictors, and survival for reconstruction in IBC patients in the United States.

Methods: Women who underwent mastectomy with or without reconstruction for IBC between 2004 and 2016 were included from the National Cancer Database. Predictors for undergoing reconstruction and association with overall survival were determined.

Results: Of 12,544 patients with IBC who underwent mastectomy, 1307 underwent reconstruction. Predictors of reconstruction included younger age, private insurance, higher income, performance of contralateral prophylactic mastectomy, and location within a metropolitan area ( < 0.001). The proportion of women having reconstruction for IBC increased from 7.3% to 12.3% from 2004 to 2016. Median unadjusted overall survival was higher in the reconstructive group l [93.7 months, 95% confidence interval (CI) 75.2-117.5] than the nonreconstructive group (68.1 months, 95% CI 65.5-71.7, hazard ratio = 0.79 95% CI 0.72-0.88, < 0.001). With adjustment for covariates, differences in overall mortality were not significant, with hazard ratio of 0.95 (95% CI 0.85-1.06, = 0.37).

Conclusions: Reconstruction rates for IBC are increasing. Women with IBC who undergo reconstruction tend to be younger and are not at the increased risk of all-cause mortality compared to those not having reconstruction. The National Cancer Database does not differentiate immediate from delayed reconstruction. However, the outcomes of immediate reconstruction in carefully selected patients with IBC should be further studied to evaluate its safety. This could impact current guidelines, which are based largely on an expert opinion.
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April 2021

Ten-Year Update of a Randomized, Prospective Trial of Conventional Fractionated Versus Moderate Hypofractionated Radiation Therapy for Localized Prostate Cancer.

J Clin Oncol 2020 05 2;38(15):1676-1684. Epub 2020 Mar 2.

Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA.

Purpose: The previously published single institution randomized prospective trial failed to show superiority in the 5-year biochemical and/or clinical disease failure (BCDF) rate with moderate hypofractionated intensity-modulated radiation therapy (H-IMRT) versus conventionally fractionated IMRT (C-IMRT). We now present 10-year disease outcomes using updated risk groups and definitions of biochemical failure.

Methods: Men with protocol-defined intermediate- and high-risk prostate adenocarcinoma were randomly assigned to receive C-IMRT (76 Gy in 38 fractions) or H-IMRT (70.2 Gy in 26 fractions). Men with high-risk disease were all prescribed 24 months of androgen deprivation therapy (ADT) and had lymph node irradiation. Men with intermediate risk were prescribed 4 months of ADT at the discretion of the treating physician. The primary endpoint was cumulative incidence of BCDF. We compared disease outcomes and overall mortality by treatment arm, with sensitivity analyses for National Comprehensive Cancer Network (NCCN) risk group adjustment.

Results: Overall, 303 assessable men were randomly assigned to C-IMRT or H-IMRT. The median follow-up was 122.9 months. Per updated NCCN risk classification, there were 28 patients (9.2%) with low-risk, 189 (62.4%) with intermediate-risk, and 86 (28.4%) with high-risk prostate cancer. The arms were equally balanced for clinicopathologic factors, except that there were more black patients in the C-IMRT arm (17.8% 7.3%; = .02). There was no difference in ADT use ( = .56). The 10-year cumulative incidence of BCDF was 25.9% in the C-IMRT arm and was 30.6% in the H-IMRT arm (hazard ratio, 1.31; 95% CI, 0.82 to 2.11). The two arms also had similar cumulative 10-year rates of biochemical failure, prostate cancer-specific mortality, and overall mortality; however, the 10-year cumulative incidence of distant metastases was higher in the H-IMRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%).

Conclusion: H-IMRT failed to demonstrate superiority compared with C-IMRT in long-term disease outcomes.
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May 2020

Overall tumor genomic instability: an important predictor of recurrence-free survival in patients with localized clear cell renal cell carcinoma.

Cancer Biol Ther 2020 05 1;21(5):424-431. Epub 2020 Mar 1.

Genomics Facility, Fox Chase Cancer Center, Philadelphia, PA, USA.

Measurement of a tumor's overall genomic instability has gathered recent interest over the identification of specific genomic imbalances, as it may provide a more robust measure of tumor aggressiveness. Here we demonstrate the association of tumor genomic instability in the prediction of disease recurrence in patients with clinically localized clear cell renal cell carcinoma (ccRCC). Genomic copy number analysis was performed using SNP-based microarrays on tumors from 103 ccRCC patients. The number of copy number alterations (CNAs) for each tumor was calculated, and a genomic imbalance threshold (GIT) associated with high stage and high-grade disease was determined. Cox proportional hazards regression analyzes were performed to assess the effect of GIT on recurrence-free survival adjusting for known confounders. In the cohort, copy number losses in chromosome arms 3p, 14q, 6q, 9p, and 1p and gains of 5q and 7p/q were common. CNA burden significantly increased with increasing stage ( < .001) and grade ( < .001). The median CNA burden associated with patients presenting with advanced stage (IV) and high-grade (III/IV) tumors was ≥9, defining the GIT. On regression analysis, GIT was a superior predictor of recurrence (Hazard Ratio 4.44 [CI 1.36-14.48], = .01) independent of stage, with similar results adjusting for grade. These findings were confirmed using an alternative measure of genomic instability, weighted Genomic Integrity Index. Our data support a key role for genomic instability in ccRCC progression. More importantly, we have identified a GIT (≥ 9 CNAs) that is a superior and independent predictor of disease recurrence in high-risk ccRCC patients.
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May 2020

Breakfast in the Classroom Initiative and Students' Breakfast Consumption Behaviors: A Group Randomized Trial.

Am J Public Health 2020 04 20;110(4):540-546. Epub 2020 Feb 20.

Katherine W. Bauer and Heidi M. Weeks are with the Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor. Gary D. Foster is with WW International (formerly known as Weight Watchers), New York, NY. Heather M. Polonsky and Jennifer O. Fisher are with the Center for Obesity Research and Education, College of Public Health, Temple University, Philadelphia, PA. Adam Davey is with the College of Health Sciences and the Department of Behavioral Health and Nutrition, University of Delaware, Newark. Sandy Sherman, Michelle L. Abel, and Lauren C. Dale are with The Food Trust, Philadelphia. Karen J. Ruth is with the Fox Chase Cancer Center, Temple Health, Philadelphia.

To identify the effect of a Breakfast in the Classroom (BIC) initiative on the foods and drinks students consume in the morning. Sixteen public schools in Philadelphia, Pennsylvania, that provide universal breakfast participated in a group randomized trial to examine the effects of BIC with complementary nutrition promotion between 2013 and 2016. Control schools (n = 8) offered breakfast in the cafeteria before school. Baseline data were collected from 1362 students in grades 4 to 6. Endpoint data were collected after 2.5 years. Students self-reported the foods and drinks they consumed in the morning. At endpoint, there was no effect of the intervention on breakfast skipping. Nearly 30% of intervention students consumed breakfast foods or drinks from multiple locations, as compared with 21% of control students. A greater proportion of intervention students than control students consumed 100% juice, and a smaller proportion consumed sugar-sweetened beverages and foods high in saturated fat and added sugar. A BIC initiative led to improvements in the types of foods and drinks students consumed in the morning. However, the program did not reduce breakfast skipping and increased the number of locations where students ate.
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April 2020

Effect of a Breakfast in the Classroom Initiative on Obesity in Urban School-aged Children: A Cluster Randomized Clinical Trial.

JAMA Pediatr 2019 04;173(4):326-333

Center for Obesity Research and Education, College of Public Health, Temple University, Philadelphia, Pennsylvania.

Importance: Serving breakfast in the classroom is promoted to increase participation in the federal School Breakfast Program. However, little is known about the effect of breakfast in the classroom on children's weight status.

Objective: To evaluate the effect of a breakfast in the classroom initiative, which combined breakfast in the classroom with breakfast-specific nutrition education, on overweight and obesity among urban children in low-income communities.

Design, Setting, And Participants: A cluster-randomized clinical trial among 1362 fourth- through sixth-grade students from low-income urban communities across 2.5 years. Sixteen kindergarten through eighth grade Philadelphia public schools with universal breakfast participated. Participants were recruited in September 2013, and the intervention began in January 2014. Data analysis took place from April 1, 2018, to August 30, 2018.

Interventions: Intervention schools received a program that included breakfast in the classroom and breakfast-specific nutrition education. Control schools continued breakfast before school in the cafeteria and standard nutrition education.

Main Outcomes And Measures: The primary outcome was the combined incidence of overweight and obesity. Secondary outcomes included the combined prevalence of overweight and obesity, incidence and prevalence of obesity, changes in body mass index (BMI) z score, and School Breakfast Program participation.

Results: Among the 1362 students, mean (SD) age was 10.8 (0.96) years and 700 (51.4%) were female; 907 (66.6%) were black, 233 (17.1%) were Hispanic, 100 (7.3%) were white, 83 (6.1%) were Asian, and 39 were of multiple or other race/ethnicity. After 2.5 years, students in intervention schools had participated in the School Breakfast Program 53.8% of days, compared with 24.9% of days among students in control schools (β = 0.33; 95% CI, 0.22-0.42). There was no difference between intervention and control schools in the combined incidence of overweight and obesity after 2.5 years (11.7% vs 9.3%; odds ratio [OR] 1.31; 95% CI, 0.85-2.02; P = .22). However, the incidence (11.6% vs 4.4%; OR, 2.43; 95% CI, 1.47-4.00) and prevalence (28.0% vs 21.2%; OR, 1.46; 95% CI, 1.11-1.92) of obesity were higher in intervention schools than in control schools after 2.5 years.

Conclusions And Relevance: A breakfast in the classroom initiative increased participation in the School Breakfast Program and did not affect the combined incidence of overweight and obesity. However, the initiative had an unintended consequence of increasing incident and prevalent obesity. Further research is needed to identify approaches to increase participation in the School Breakfast Program that do not increase obesity among students.

Trial Registration: identifier: NCT01924130.
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April 2019

Title: efficacy of a food parenting intervention for mothers with low income to reduce preschooler's solid fat and added sugar intakes: a randomized controlled trial.

Int J Behav Nutr Phys Act 2019 01 17;16(1). Epub 2019 Jan 17.

Providence Health and Services, Center for Outcomes Research & Education, 5251 NE Gilsan Street, Bldg A, Portland, OR, 97213, USA.

Background: Few interventions have shown efficacy to influence key energy balance behaviors during the preschool years.

Objective: A randomized controlled trial (RCT) was used to evaluate the efficacy of Food, Fun, and Families (FFF), a 12 week authoritative food parenting intervention for mothers with low-income levels, to reduce preschool-aged children's intake of calories from solid fat and added sugar (SoFAS).

Methods: Mothers were randomly assigned to receive FFF (n = 59) or to a delayed treatment control (n = 60). The primary outcome was children's daily energy intake from SoFAS at the end of the 12 week intervention, controlling for baseline levels, assessed by 24-h dietary recalls. Secondary outcomes included children's daily energy intake, children's BMI z-scores, and meal observations of maternal food parenting practices targeted in FFF (e.g. providing guided choices).

Results: Participating mothers were predominantly African American (91%), with 39% educated beyond high school and 66% unemployed. Baseline demographics and child SoFAS intakes did not differ by group. Lost to follow-up was 13% and did not differ between groups. At post-intervention, FFF children consumed ~ 94 kcal or 23% less daily energy from SoFAS than children in the control group, adjusting for baseline levels (307.8 (95%CI = 274.1, 341.5) kcal vs. 401.9 (95%CI = 369.8, 433.9) kcal, FFF vs. control; p < 0.001). FFF mothers also displayed a greater number of authoritative parenting practices when observed post-intervention with their child at a buffet-style meal (Wilcoxon z = - 2.54, p = 0.012). Neither child total daily energy intake nor BMI z-scores differed between groups post-intervention.

Conclusions: Findings demonstrate the initial efficacy of an authoritative food parenting intervention for families with low-income to reduce SoFAS intake in early childhood. Additional research is needed to evaluate longer-term effects on diet and growth.

Trial Registration: Retrospectively registered at : #NCT03646201.
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January 2019

Predictive Value of Leukocyte- and Platelet-Derived Ratios in Rectal Adenocarcinoma.

J Surg Res 2018 12 14;232:275-282. Epub 2018 Jul 14.

Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Background: Advances in treatment of rectal cancer have improved survival, but there is variability in response to therapy. Recent data suggest the utility of the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in predicting survival. Our aim was to examine these ratios in rectal cancer patients and determine whether any association exists with overall survival (OS).

Methods: Using prospectively maintained institutional data, a query was completed for clinical stage II-III rectal adenocarcinoma patients treated from 2002 to 2016. We included patients who had a complete blood count collected before neoadjuvant chemoradiation (pre-CRT) and again before surgery (post-CRT). The LMR, NLR, and PLR were calculated for the pre-CRT and post-CRT time points. Potential cutpoints associated with OS differences were determined using maximally selected rank statistics. Survival curves were compared using log-rank tests and were adjusted for age and stage using Cox regression.

Results: A total of 146 patients were included. Cutpoints were significantly associated with OS for pre-CRT ratios but not for post-CRT ratios. Within the pretreatment group, a "low" (<2.86) LMR was associated with decreased OS (log-rank P = 0.004). In the same group, a "high" (>4.47) NLR and "high" PLR (>203.6) were associated with decreased OS (log-rank P < 0.001). With covariate adjustment for age, and separately for final pathologic stage, the associations between OS and LMR, NLR, and PLR each retained statistical significance.

Conclusions: If obtained before the start of neoadjuvant chemoradiation, LMR, NLR, and PLR values are accurate predictors of 5-y OS in patients with locally advanced rectal adenocarcinoma.
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December 2018

The Utility of Preoperative Vascular Grading in Patients Undergoing Surgery First for Pancreatic Cancer: Does Radiologic Arterial or Venous Involvement Predict Pathologic Margin Status?

J Oncol 2018 13;2018:7675262. Epub 2018 Aug 13.

Department of Surgical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.

Controversy exists on accurately grading vascular involvement on preoperative imaging for pancreatic ductal adenocarcinoma. We reviewed the association between preoperative imaging and margin status in 137 patients. Radiologists graded venous involvement based on the Ishikawa classification system and arterial involvement based on preoperative imaging. For patients with both classifications recorded, we categorized vascular involvement as "None," "Arterial only," "Venous only," or "Both" and examined the association of vascular involvement and pathologic margin status. Of 134 patients with Ishikawa classifications, 63%, 17%, 11%, and 9% were graded as I, II, III, and IV, respectively. Of 96 patients with arterial staging, 74%, 16%, and 10% were categorized as stages i, ii, and iii, respectively. Of 93 patients with both stagings, 61% had no vascular involvement, 7% had arterial only, 14% had venous only, and 17% had both involved. Ishikawa classification was strongly associated with a positive SMA and SMV margin (p<0.001). However, for arterial staging, there was no association with SMA or SMV margin. Overall, Ishikawa grading was more predicative of arterial involvement and remained significant on multivariate analysis. The use of diagnostic imaging in predicting positive margins is more accurate when using a venous grading system.
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August 2018

Pathologic response following treatment for locally advanced rectal cancer: Does location matter?

J Surg Res 2018 04 4;224:215-221. Epub 2018 Jan 4.

Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Background: Despite advances in the treatment of rectal adenocarcinoma, the management of locally advanced disease remains a challenge. The standard of care for patients with stages II and III rectal cancer includes neoadjuvant chemoradiation followed by total mesorectal excision and postoperative chemotherapy. Much effort has been dedicated to the identification of predictive factors associated with pathologic complete response (pCR). The aim of our study was to examine our institutional experience and determine whether any association exists between anatomic tumor location and the rate of pCR. We hypothesized that lesions more than 6 cm from the anal verge are more likely to achieve a pCR.

Methods: Using data from our prospectively maintained tumor registry, a query was completed to identify all patients with locally advanced rectal adenocarcinoma who underwent treatment at Fox Chase Cancer Center from 2002 to 2015. Demographics, pretreatment, posttreatment, and final pathologic TNM staging data were collected as well as treatment intervals in days, recurrence status, overall survival, and disease-free survival. Patients with incomplete endoscopic data, staging information, survival, or recurrence status were excluded. The primary outcome measured was the degree of pathologic response. Logistic regression was used to adjust for covariates.

Results: Of the 135 patients eligible in the study cohort, 39% were female and 61% were male. Regarding initial clinical stage, 43% were stage II and 57% were stage III. A total of 29% had a pCR, 43% had partial pathologic response, and 28% had no response to neoadjuvant treatment. Tumor location ranged from 0 to 13 cm from the anal verge. Longitudinal tumor length was recorded in 111 patients, facilitating the calculation of mean tumor distance from the anal verge. This ranged from 0 to 15.5 cm. Univariate and multivariable analyses were completed using pCR as a primary outcome. No statistically significant difference was noted based on tumor location, regardless of measurement approach.

Conclusions: Anatomic location of cancer of the rectum does not affect pCR after neoadjuvant therapy and subsequent surgical resection.
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April 2018

Benefits of Supplemental Jejunostomy Tube Feeding During Neoadjuvant Therapy in Patients with Locally Advanced, Potentially Resectable Esophageal Cancer.

J Laparoendosc Adv Surg Tech A 2017 Dec 4;27(12):1279-1283. Epub 2017 Aug 4.

Fox Chase Cancer Center , Philadelphia, Pennsylvania.

Background: Standard treatment for locally advanced esophageal cancer includes neoadjuvant therapy followed by surgical resection. However, many patients experience a period of decreased oral intake during neoadjuvant treatment and are at risk for malnutrition. We hypothesize that use of jejunostomy tube (j-tube) feedings during neoadjuvant therapy in selected patients may be associated with better perioperative outcomes.

Methods: A prospectively collected database at a single institution was retrospectively analyzed. The study period was from 2005 to 2015. Patients who underwent j-tube placement before neoadjuvant therapy before definitive resection for esophageal cancer were included in the analysis. Perioperative outcomes were compared between patients who adhered to recommended tube feeds during neoadjuvant therapy (users) and patients who did not adhere (nonusers).

Results: During the study period, 94/301 patients received a j-tube before or during neoadjuvant therapy for esophageal cancer. Seventy-three patients utilized tube feeds regularly during the neoadjuvant phase, while 21 patients did not. The groups did not differ significantly with respect to clinical factors such as dysphagia on presentation, postneoadjuvant therapy performance status, or Charlson Comorbidity Index. Perioperative pneumonia rates were lower in j-tube users compared to nonusers (6.8% [5 of 73] versus 23.8% [5 of 21]), respectively, P = .036); this difference remained significant with adjustment for type of surgery (odds ratio = 0.16, P = .018).

Conclusions: j-Tube users had a significantly lower incidence of pneumonia within 30 days of curative resection when compared to nonusers. j-Tube feedings during neoadjuvant therapy for selected patients with locally advanced esophageal cancer should be encouraged.
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December 2017

LincIN, a novel NF90-binding long non-coding RNA, is overexpressed in advanced breast tumors and involved in metastasis.

Breast Cancer Res 2017 05 30;19(1):62. Epub 2017 May 30.

Cancer Epigenetics Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.

Background: Recent genome-wide profiling by sequencing and distinctive chromatin signatures has identified thousands of long non-coding RNA (lncRNA) species (>200 nt). LncRNAs have emerged as important regulators of gene expression, involving in both developmental and pathological processes. While altered expression of lncRNAs has been observed in breast cancer development, their roles in breast cancer progression and metastasis are still poorly understood.

Methods: To identify novel breast cancer-associated lncRNA candidates, we employed a high-density SNP array-based approach to uncover intergenic lncRNA genes that are aberrantly expressed in breast cancer. We first evaluated the potential value as a breast cancer prognostic biomarker for one breast cancer-associated lncRNA, LincIN, using a breast cancer cohort retrieved from The Cancer Genome Atlas (TCGA) Data Portal. Then we characterized the role of LincIN in breast cancer progression and metastasis by in vitro invasion assay and a mouse tail vein injection metastasis model. To study the action of LincIN, we identified LincIN-interacting protein partner(s) by RNA pull-down experiments followed with protein identification by mass spectrometry.

Results: High levels of LincIN expression are frequently observed in tumors compared to adjacent normal tissues, and are strongly associated with aggressive breast cancer. Importantly, analysis of TCGA data further suggest that high expression of LincIN is associated with poor overall survival in patients with breast cancer (P = 0.044 and P = 0.011 after adjustment for age). The functional experiments demonstrate that knockdown of LincIN inhibits tumor cell migration and invasion in vitro, which is supported by the results of transcriptome analysis in the LincIN-knockdown cells. Furthermore, knockdown of LincIN diminishes lung metastasis in a mouse tail vein injection model. We also identified a LincIN-binding protein, NF90, through which overexpression of LincIN may repress p21 protein expression by inhibiting its translation, and upregulation of p21 by LincIN knockdown may be associated with less aggressive metastasis phenotypes.

Conclusions: Our studies provide clear evidence to support LincIN as a new regulator of tumor progression-metastasis at both transcriptional and translational levels and as a promising prognostic biomarker for breast cancer.
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May 2017

Mutational studies on single circulating tumor cells isolated from the blood of inflammatory breast cancer patients.

Breast Cancer Res Treat 2017 Jun 7;163(2):219-230. Epub 2017 Mar 7.

Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.

Purpose: The molecular characterization of circulating tumor cells (CTCs) is critical to identify the key drivers of cancer metastasis and devising therapeutic approaches, particularly for inflammatory breast cancer (IBC) which is usually diagnosed at advance stages and progresses rapidly.

Methods: Genomic alterations in tumor tissue samples were studied using Foundation One™. Single CTCs were isolated using CellSearch followed by single-cell isolation by DEPArray™. Samples with 20 or more CTCs were chosen to isolate single CTCs using the DEPArray™.

Results: Genomic alterations were studied in primary tumor or metastatic sites from 32 IBC patients. Genes with high-frequency mutations were as follows: TP53 (69%), RB1 (16%), PIK3CA (13%), and also ErbB2 (3%). At least once during treatment, CTCs were detected in 26 patients with metastatic IBC, in two patients with locally advanced IBC, and four patients had no detectable CTCs. Per 7.5 mL of blood, fifteen patients (47%) had ≥20 CTCs and six of them were chosen at random to isolate single CTCs. These cells were tested for the presence of TP53, RB1, PIK3CA, and/or ErbB2 mutations previously found in matching tissue biopsies. The isolated CTCs showed the same mutations as primary or metastatic tumor samples. Intra-patient CTC heterogeneity was found by the presence of different CTC subclones, with some CTCs harboring different combinations of mutated and wild-type genes.

Conclusions: Our results indicate that CTCs could represent a non-invasive source of cancer cells from which to determine genetic markers as the disease progresses and identify potential therapeutic targets in IBC patients.
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June 2017

The need for androgen deprivation therapy in patients with intermediate-risk prostate cancer treated with dose-escalated external beam radiation therapy.

Can J Urol 2017 Feb;24(1):8656-8662

Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.

Introduction: To evaluate if androgen deprivation therapy (ADT) improves outcomes for patients with localized, intermediate-risk prostate cancer treated with definitive external beam radiation therapy (EBRT) in the dose-escalated era.

Materials And Methods: This is a retrospective study using a single institutional database. We included patients with localized, intermediate-risk prostate cancer treated with dose-escalated radiation therapy (RT) with 3D conformal radiotherapy or intensity-modulated radiotherapy (74-80 Gy in daily fraction of 1.8 Gy-2.0 Gy, or 70.2 Gy in daily fraction of 2.7 Gy) from 1992 to 2013. To further risk stratify the patients, PSA 10 ng/mL-20 ng/mL, Gleason 3+4, and T2b-T2c were assigned risk score (RS) of 1, while Gleason 4+3 was assigned RS of 2. Patients with prior treatment for prostate cancer, those on long term ADT (>= 23 months), or those with follow up < 1 year were excluded. We defined initial ADT as initiation within 9 months prior to the start of RT, during RT, or within 2 months after the completion of RT. Outcomes for patients who received initial ADT were compared to men treated with RT alone. Covariates included number of intermediate risk factors, age, and baseline comorbidities. Kaplan Meier estimates were compared using log rank tests. Competing risk regression and Cox proportional hazards regression were used to estimate hazard ratios adjusted for covariates.

Results: Of 1,134 patients included in this study, 155 received initial ADT with median duration of 4.0 months (m) (range 0.5 m-22.0 m). The median follow up was 56.4 m (range 12.3 m-200.7 m). Patients on ADT had higher RS compared to those with radiation alone (RS 1: 48% versus 58%; RS 2: 35% versus 32%; RS 3: 14% versus 9%; RS 4: 3% versus 1%; p=0.01). When patients with ADT were compared to those treated with radiation alone, there were no significant differences in freedom from biochemical failure (FFBF) (84.0% versus 87.3%, p = 0.83), freedom from distant metastasis (FFDM) (94.4% versus 96.9%, p = 0.41), or overall survival (OS) (92.3% versus 90.7%, (p = 0.48) at 5 years. Among patients with RS >= 2, there were still no significant differences in FFBF, FFDM, or OS when patients treated with ADT were compared to those treated with radiation alone. In multivariable analyses adjusting for RS and age, the adjusted hazard ratio for ADT use was sHR = 0.89 (95% CI = 0.64-1.66, p = 0.64) for BCF; sHR = 1.13 (95% CI = 0.48-2.65, p = 0.77) for DM. For overall mortality, adjusted HR = 1.23 (95% CI = 0.76-2.01, p = 0.40) where comorbidities (including diabetes, cardiac disease, and hypertension) were also included as covariates.

Conclusion: Our study suggested that treatment of intermediate-risk prostate cancer with definitive dose-escalated EBRT alone resulted in acceptable outcomes, and it failed to show improved outcomes in patients who received short term ADT.
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February 2017

Young Age Increases Risk of Lymph Node Positivity in Early-Stage Rectal Cancer.

J Natl Cancer Inst 2016 Jan;108(1)

Background: The risk of lymph node positivity (LN+) in rectal cancer is a parameter that impacts therapeutic recommendations. We aimed to quantify the effect of younger age on LN+ in rectal cancer.

Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, patients with rectal cancer diagnosed between 1988 and 2008 were identified. Patients were stage I-III, without preoperative radiotherapy, at least one lymph node examined, and a standard rectal cancer operation performed. The association of age and LN+ status was examined with logistic regression separately for each T stage, adjusting for multiple covariates. Poisson regression was used to evaluate age and number of positive lymph nodes (LNs). All statistical tests were two-sided.

Results: Fifty-six thousand seventy-six patients were identified, including 1194 (2.1%) patients age 20 to 39 years at diagnosis and 4199 (7.5%) patients age 40 to 49 years (defined as young). For each T stage, LN+ was inversely associated with age (all P < .001). For T1, T2, and T3, age remained predictive of LN+ status after adjustment for number of LNs examined and other covariates (P < .001 for each stage). Adjusted odds ratios (ORs) for LN+ for age 20 to 39 vs 60 to 69 were: T1: 1.97(95% confidence interval [CI] = 1.36 to 2.86); T2: 1.48 (95% CI = 1.13 to 1.95); T3: 1.30 (95% CI = 1.10 to 1.53). Young age was a statistically significant predictor of an increased number of LNs positive for stage T2 (P = .042) and T3 (P = .002).

Conclusion: In this large national dataset, young age at diagnosis is associated with an increased risk of LN+. This finding merits further investigation and may ultimately impact treatment decision-making for young early-stage patients.
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January 2016

Interest in genomic SNP testing for prostate cancer risk: a pilot survey.

Hered Cancer Clin Pract 2015 8;13(1):11. Epub 2015 Apr 8.

Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA USA.

Background: Advancements in genomic testing have led to the identification of single nucleotide polymorphisms (SNPs) associated with prostate cancer. The clinical utility of SNP tests to evaluate prostate cancer risk is unclear. Studies have not examined predictors of interest in novel genomic SNP tests for prostate cancer risk in a diverse population.

Methods: Consecutive participants in the Fox Chase Prostate Cancer Risk Assessment Program (PRAP) (n = 40) and unselected men from surgical urology clinics (n = 40) completed a one-time survey. Items examined interest in genomic SNP testing for prostate cancer risk, knowledge, impact of unsolicited findings, and psychosocial factors including health literacy.

Results: Knowledge of genomic SNP tests was low in both groups, but interest was higher among PRAP men (p < 0.001). The prospect of receiving unsolicited results about ancestral genomic markers increased interest in testing in both groups. Multivariable modeling identified several predictors of higher interest in a genomic SNP test including higher perceived risk (p = 0.025), indicating zero reasons for not wanting testing (vs ≥1 reason) (p = 0.013), and higher health literacy (p = 0.016).

Conclusions: Knowledge of genomic SNP testing was low in this sample, but higher among high-risk men. High-risk status may increase interest in novel genomic tests, while low literacy may lessen interest.
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April 2015

Cost sharing and hereditary cancer risk: predictors of willingness-to-pay for genetic testing.

J Genet Couns 2014 Dec 6;23(6):1002-11. Epub 2014 May 6.

Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA, 19111, USA,

Increasing use of predictive genetic testing to gauge hereditary cancer risk has been paralleled by rising cost-sharing practices. Little is known about how demographic and psychosocial factors may influence individuals' willingness-to-pay for genetic testing. The Gastrointestinal Tumor Risk Assessment Program Registry includes individuals presenting for genetic risk assessment based on personal/family cancer history. Participants complete a baseline survey assessing cancer history and psychosocial items. Willingness-to-pay items include intention for: genetic testing only if paid by insurance; testing with self-pay; and amount willing-to-pay ($25-$2,000). Multivariable models examined predictors of willingness-to-pay out-of-pocket (versus only if paid by insurance) and willingness-to-pay a smaller versus larger sum (≤$200 vs. ≥$500). All statistical tests are two-sided (α = 0.05). Of 385 evaluable participants, a minority (42%) had a personal cancer history, while 56% had ≥1 first-degree relative with colorectal cancer. Overall, 21.3% were willing to have testing only if paid by insurance, and 78.7% were willing-to-pay. Predictors of willingness-to-pay were: 1) concern for positive result; 2) confidence to control cancer risk; 3) fewer perceived barriers to colorectal cancer screening; 4) benefit of testing to guide screening (all p < 0.05). Subjects willing-to-pay a higher amount were male, more educated, had greater cancer worry, fewer relatives with colorectal cancer, and more positive attitudes toward genetic testing (all p < 0.05). Individuals seeking risk assessment are willing-to-pay out-of-pocket for genetic testing, and anticipate benefits to reducing cancer risk. Identifying factors associated with willingness-to-pay for genetic services is increasingly important as testing is integrated into routine cancer care.
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December 2014

Build it, and will they come? Unexpected findings from a study on a Web-based intervention to improve colorectal cancer screening.

J Health Commun 2012 22;17(1):41-53. Epub 2011 Jun 22.

Fox Chase Cancer Center, 510 Township Line Road, Cheltenham, PA 19012, USA.

Given the extensive use of the Internet for health information, Web-based health promotion interventions are widely perceived as an effective communication channel. The authors conducted this study to determine use of a Web-based intervention intended to improve colorectal cancer screening in a population of women who are at average risk and noncompliant to current screening recommendations. The study was a randomized controlled trial designed to compare the effectiveness of colorectal cancer screening educational materials delivered using the Internet versus a printed format. In 3 years, 391 women seen for routine obstetrics/gynecology follow-up at 2 academic centers provided relevant survey information. Of these, 130 were randomized to the Web intervention. Participants received voluntary access to a password-protected, study-specific Web site that provided information about colorectal cancer and colorectal cancer screening options. The main outcome measures were self-reported and actual Web site use. Only 24.6% of women logged onto the Web site. Age was the only variable that differentiated users from nonusers (p = .03). In contrast, 16% of participants self-reported Web use. There was significant discordance between the veracity of actual and self-reported use (p = .004). Among true users, most (81%) logged on once only. These findings raise questions about how to increase use of important health communication interventions.
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March 2012

Radiotherapy doses of 80 Gy and higher are associated with lower mortality in men with Gleason score 8 to 10 prostate cancer.

Int J Radiat Oncol Biol Phys 2012 Apr 15;82(5):1949-56. Epub 2011 Jul 15.

Department of Radiation Oncology, Cooper University Hospital, Camden, NJ, USA.

Purpose: Men with Gleason score (GS) 8-10 prostate cancer (PCa) are assumed to have a high risk of micrometastatic disease at presentation. However, local failure is also a major problem. We sought to establish the importance of more aggressive local radiotherapy (RT) to ≥80 Gy.

Methods And Materials: There were 226 men treated consecutively with RT ± ADT from 1988 to 2002 for GS 8-10 PCa. Conventional, three-dimensional conformal or intensity-modulated (IM) RT was used. Radiation dose was divided into three groups: (1) <75 Gy (n = 50); (2) 75-79.9 Gy (n = 60); or (3) ≥80 Gy (n = 116). The endpoints examined included biochemical failure (BF; nadir + 2 definition), distant metastasis (DM), cause-specific mortality, and overall mortality (OM).

Results: Median follow-up was 66, 71, and 58 months for Groups 1, 2, and 3. On Fine and Gray's competing risk regression analysis, significant predictors of reduced BF were RT dose ≥80 Gy (p = 0.011) and androgen deprivation therapy duration ≥24 months (p = 0.033). In a similar model of DM, only RT dose ≥80 Gy was significant (p = 0.007). On Cox regression analysis, significant predictors of reduced OM were RT dose ≥80 Gy (p = 0.035) and T category (T3/4 vs. T1, p = 0.041). Dose was not a significant determinant of cause-specific mortality. Results for RT dose were similar in a model with RT dose and ADT duration as continuous variables.

Conclusion: The results indicate that RT dose escalation to ≥80 Gy is associated with lower risks of BF, DM, and OM in men with GS 8-10 PCa, independently of androgen deprivation therapy.
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April 2012

Phase II study of paclitaxel, carboplatin, and cetuximab as first line treatment, for patients with advanced non-small cell lung cancer (NSCLC): results of OPN-017.

J Thorac Oncol 2008 Nov;3(11):1286-92

Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.

Background: Cetuximab has demonstrated synergy with taxanes in preclinical models; as well as single agent activity. We assessed the activity of cetuximab with carboplatin and paclitaxel given on a 4-week schedule, in advanced, chemo-naive non-small cell lung cancer.

Patients And Methods: This phase II, single arm, multi-institution study featured standard dosage of cetuximab 400 mg/m day 1, then 250 mg/m with paclitaxel (100 mg/m/wk, for 3 weeks), and carboplatin (area under curve = 6) day 1 of each 28 day cycle. After 4 to 6 cycles, in the absence of disease progression or excess toxicity, cetuximab was continued weekly. Primary end point was response rate.

Results: Fifty-three patients (median age 63, 51% male) participated. Response rate was 57% (3 complete response and 27 partial response). At a median follow-up of 12.5 months, the estimated overall survival is 13.8 months (95% CI: 9.08-16.02) with an event-free survival rate of 5.53 months (95% CI: 4.77-7.99), 18.9% remain free from progression at 1 year. Improved survival was associated with female gender, absence of prior radiation, PS 0 and epidermal growth factor receptor expression. Toxicities included rash (28% grade 3), nail changes (3.7% grade 3), hypomagnesemia (7.5% grade 3 and 3.7% grade 4), and neutropenia (25% grade 3 and 13% grade 4) in addition to other typical side effects anticipated with paclitaxel/carboplatin. There were no grade 5 toxicities.

Conclusion: Combination of cetuximab/paclitaxel/carboplatin in non-small cell lung cancer was well tolerated and clinically active with manageable toxicities. This unique schedule, integrating weekly paclitaxel and cetuximab has not yet been tested in a randomized trial.
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November 2008

Promising survival in patients with recurrent non-small cell lung cancer treated with docetaxel and gemcitabine in combination as second-line therapy.

J Thorac Oncol 2008 Sep;3(9):1032-8

University of Kansas Medical Center, Veterans Administration Medical Center, Kansas City, Missouri, USA.

Introduction: Lung cancer is the leading cause of cancer death in men and women, and current second-line chemotherapy regimens yield relatively poor response and survival rates.

Hypothesis: We hypothesized that the combination of weekly docetaxel (D) and gemcitabine (G) would show activity in the second-line setting. We therefore conducted a phase II trial evaluating this regimen in patients with relapsed or progressive non-small cell lung cancer (NSCLC) after first-line platinum-based therapy.

Methods: Patients with recurrent NSCLC, adequate physiologic indices, and exposure to one prior platinum-based regimen were eligible. Docetaxel 40 mg/m intravenous (IV) and gemcitabine (G) 800 mg/m IV weekly were administered on day 1 and 8 every 21 days. In the absence of dose-limiting toxicity, G was escalated on an intrapatient basis to 1 g/m/wk. The primary endpoint was response rate (RR); event-free (EFS) and overall survival were secondary endpoints.

Results: Thirty-five patients (median age 61 years; 20 [57%] male) were accrued. Most (88%) had previously received carboplatin/paclitaxel, 31.4% in combination with a third investigational agent, more than half (57.1%) had prior radiation. The median number of cycles was four. RR was 23%. Median EFS was 5.7 months and median overall survival was 12.5 months. Patients who had their cancer diagnosed more than or equal to 12 months before entering the trial had superior EFS (13.7 months versus 4.8 months). Toxicity was acceptable. There were no treatment-related deaths.

Conclusions: A nonplatinum doublet with GD is feasible and effective in the treatment of recurrent, platinum-exposed NSCLC patients. RR and survival are promising.
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September 2008

Impact of pelvic nodal irradiation with intensity-modulated radiotherapy on treatment of prostate cancer.

Int J Radiat Oncol Biol Phys 2006 Oct;66(2):583-92

Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.

Purpose: The aim of this study was to evaluate the feasibility of treating the pelvic lymphatic regions during prostate intensity-modulated radiotherapy (IMRT) with respect to our routine acceptance criteria.

Methods And Materials: A series of 10 previously treated prostate patients were randomly selected and the pelvic lymphatic regions delineated on the fused magnetic resonance/computed tomography data sets. A targeting progression was formed from the prostate and proximal seminal vesicles only to the inclusion of all pelvic lymphatic regions and presacral region resulting in 5 planning scenarios of increasing geometric difficulty. IMRT plans were generated for each stage for two accelerator manufacturers. Dose volume histogram data were analyzed with respect to dose to the planning target volumes, rectum, bladder, bowel, and normal tissue. Analysis was performed for the number of segments required, monitor units, "hot spots," and treatment time.

Results: Both rectal endpoints were met for all targets. Bladder endpoints were not met and the bowel endpoint was met in 40% of cases with the inclusion of the extended and presacral lymphatics. A significant difference was found in the number of segments and monitor units with targeting progression and between accelerators, with the smaller beamlets yielding poorer results. Treatment times between the 2 linacs did not exhibit a clinically significant difference when compared.

Conclusions: Many issues should be considered with pelvic lymphatic irradiation during IMRT delivery for prostate cancer including dose per fraction, normal structure dose/volume limits, planning target volumes generation, localization, treatment time, and increased radiation leakage. We would suggest that, at a minimum, the endpoints used in this work be evaluated before beginning IMRT pelvic nodal irradiation.
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October 2006

Eight-year blood pressure change in middle-aged men: relationship to multiple nutrients.

Hypertension 2002 May;39(5):1000-6

Northwestern University Medical School, Chicago, Illinois, USA.

Relationships of nutrients, alcohol intake, and change in weight to change in blood pressure over 8 years in 1714 employed middle-aged men from the Chicago Western Electric Study were explored. At first and second annual examinations, 2 in-depth interviews were performed to assess usual intake of foods and beverages during the preceding 28 days. Annual follow-up data through examination year 9 were used to determine change in weight and blood pressure. Averages of nutrients from 2 interviews were related to annual blood pressure change from baseline by use of the Generalized Estimating Equation, with control for confounders. In analyses of dietary variables considered individually, total and animal protein; total, saturated, monounsaturated, and polyunsaturated fatty acids; cholesterol; Keys dietary lipid score; calcium; alcohol; and average annual change in weight were positively and significantly related to average annual change in systolic pressure; vegetable protein, total carbohydrate, beta-carotene, and an antioxidant vitamin score based on vitamin C and beta-carotene were inversely and significantly related to average annual change in systolic pressure. In analyses of combinations of dietary factors, cholesterol, Keys score, and alcohol were positively related to change in systolic pressure (eg, Z-scores 2.21, 2.05, and 2.50); vegetable protein and antioxidant index were inversely related to change in systolic and diastolic pressure. Change in weight was directly related to change in systolic and diastolic pressure. These findings support the concept that multiple macro- and micronutrients, alcohol intake, and calorie imbalance relate prospectively to blood pressure change.
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May 2002

The Association of Whole Grain Intake and Fasting Insulin in a Biracial Cohort of Young Adults: The CARDIA Study.

CVD Prev 1998 Sep;1(3):231-242

Division of Epidemiology, University of Minnesota, 1300 South Second St., Ste. 300, Minneapolis, MN 55454.

Background: Whole grain consumption may influence insulin through beneficial effects on satiety and body weight, intestinal absorption, or the action of specific nutrients or constituents.

Design And Methods: We examined the associations of whole grain intake, assessed by a diet history interview at baseline (year 0) and year 7, with body mass index (BMI), waist-hip ratio (WHR), and fasting insulin in 3,627 Black and White adults in the Coronary Artery Risk Development in Young Adults Study (CARDIA). We estimated year 0 and year 7 cross-sectional associations accounting for correlation between years using repeated measures regression.

Results: After adjustment for age, education, energy intake, CARDIA field center, physical activity, alcohol consumption, and cigarette smoking, whole grain consumption was unrelated to WHR and inversely related to body mass index only in Whites at year 7. Whole grain consumption was inversely related to fasting insulin in Whites at year 0 and Black men and Whites at year 7. Mean differences for year 7 fasting insulin between the least vs. most frequent categories of whole grain consumption (0-2 vs. > 9 times/week) were 2.2, 1.0 and 1.0 U/mL in Black men, white men, and white women, respectively (p < 0.05). The inverse association of whole grain intake and fasting insulin remained significant (p < 0.05) after adjustment for body mass index. Potentially mediating nutrients explaining part of the relationship between whole grain intake and fasting insulin were dietary magnesium and fiber.

Conclusions: The independent inverse relationship between whole grain consumption and fasting insulin levels may have important public health implications in light of the low consumption of whole grains and the increasing prevalence of obesity and diabetes in the US.
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September 1998