Eleanor E Harris

East Carolina University, Гринвилл, North Carolina, United States

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Publications (62)237.84 Total impact

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    ABSTRACT: Purpose Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer. Methods and Materials RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival. Results Although RSI did not uniformly predict for LR across the entire cohort, combining RSI and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). Conclusions The combined molecular subtype-RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and molecular subtype could be useful in guiding radiation therapy-based decisions in breast cancer.
    International journal of radiation oncology, biology, physics 06/2015; 93(3). DOI:10.1016/j.ijrobp.2015.06.021 · 4.26 Impact Factor

  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S170. DOI:10.1016/j.ijrobp.2014.05.675 · 4.26 Impact Factor
  • Dan Opp · Kenneth Forster · Weiqi Li · Geoffrey Zhang · Eleanor E Harris ·
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    ABSTRACT: Postmastectomy radiation (PMRT) lowers local-regional recurrence risk and improves survival in selected patients with breast cancer. The chest wall and lower axilla are technically challenging areas to treat with homogenous doses and normal tissue sparing. This study compares several techniques for PMRT to provide data to guide selection of optimal treatment techniques. Twenty-five consecutive left-sided patients treated postmastectomy were contoured using Radiation Therapy Oncology Group (RTOG) atlas guidelines then planned using 4 different PMRT techniques: opposed tangents with wedges (3-dimensional [3D] wedges), opposed tangents with field-in-field (FiF) modulation, 8-field intensity modulation radiotherapy (IMRT), and custom bolus electron conformal therapy (BolusECT, .decimal, Inc., Sanford, FL). Required planning target volume (PTV) coverage was held constant, and then dose homogeneity and normal tissue dose parameters were compared among the 4 techniques. BolusECT achieved clincally acceptable PTV coverage for 22 out of 25 cases. Compared with either tangential technique, IMRT and BolusECT provided the lowest heart V25 doses (3.3% ± 0.9% and 6.6% ± 3.2%, respectively with p < 0.0001). FiF had the lowest mean total lung dose (7.3 ± 1.1Gy, with p = 0.0013), IMRT had the lowest total lung V20 (10.3% ± 1.6%, p < 0.0001), and BolusECT had the lowest mean heart dose (7.3 ± 2.0Gy, p = 0.0002). IMRT provided the optimal dose homogeneity and normal tissue sparing compared with all other techniques for the cases in which BolusECT could not achieve acceptable PTV coverage. IMRT generally exposes contralateral breast and lung to slightly higher doses. Optimal PMRT technique depends upon patient anatomy. Patients whose maximal target volume depth is about 5.7cm or less can be treated with BolusECT-assisted 12 or 15MeV electron beams. At these energies, BolusECT has comparable dose-volume statistics as IMRT and lower heart V25 than opposed tangential beams. Patients with larger depths are best treated with IMRT, which provides significant advantages in both dose homogeneity and normal tissue sparing compared with all other techniques.
    Medical dosimetry: official journal of the American Association of Medical Dosimetrists 12/2013; 38(4):448-53. DOI:10.1016/j.meddos.2013.08.002 · 0.76 Impact Factor
  • K. Latifi · W. Li · G.G. Zhang · E.G. Moros · E.E. Harris ·

    International Journal of Radiation OncologyBiologyPhysics 11/2012; 84(3):S245. DOI:10.1016/j.ijrobp.2012.07.636 · 4.26 Impact Factor
  • Jeremiah L Deneve · Richard A Hoefer · Eleanor E R Harris · Christine Laronga ·
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    ABSTRACT: Targeted intraoperative radiation therapy (IORT) as an alternative to whole breast irradiation (WBI) has been described for patients with early-stage breast cancer. The randomized phase III TARGiT trial demonstrated similar recurrence rates to WBI and a lower overall toxicity profi le on short-term follow-up. We report on our early North American surgical experience using the Intrabeam radiotherapy delivery system and review the current literature. Prospectively gathered estrogen receptor-positive, clinically node-negative patients with invasive breast cancer < 3 cm receiving IORT using the Intrabeam system were reviewed. IORT-related effects and early postoperative outcome were assessed. A literature review was also performed. Forty-two patients (median age 71 years) underwent lumpectomy, sentinel lymph node (SLN) biopsy, and concurrent IORT from January 2011 to July 2011. Ninety-one percent of patients had invasive ductal histology with a median tumor size of 1.0 cm. This review highlights the patient selection criteria, describes commercially available accelerated partial breast irradiation (APBI) treatment options, and discusses outcomes for the variety of APBI techniques currently utilized in clinical practice as well as an istitutional review of our early surgical experience using the Intrabeam radiotherapy delivery system. While a variety of APBI techniques are currently available for clinical use, our early North American operative experience with IORT shows it is well tolerated with low morbidity. Delivery of IORT adds moderate operative time and may require creating subcutaneous tissue fl aps. The addition of WBI may be necessary in situations for positive residual margins or microscopic nodal disease in patients who do not undergo additional surgery.
    Cancer control: journal of the Moffitt Cancer Center 10/2012; 19(4):295-308. · 3.50 Impact Factor
  • Eleanor E R Harris · Jessica Freilich · Hui-Yi Lin · Michael Chuong · Geza Acs ·
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    ABSTRACT: Purpose: Use of postmastectomy radiation therapy (PMRT) in breast cancer patients with 1-3 positive nodes is controversial. The objective of this study was to determine whether the size of nodal metastases in this subset could predict who would benefit from PMRT. Methods and materials: We analyzed 250 breast cancer patients with 1-3 positive nodes after mastectomy treated with contemporary surgery and systemic therapy at our institution. Of these patients, 204 did not receive PMRT and 46 did receive PMRT. Local and regional recurrence risks were stratified by the size of the largest nodal metastasis measured as less than or equal to 5 mm or greater than 5 mm. Results: The median follow-up was 65.6 months. In the whole group, regional recurrences occurred in 2% of patients in whom the largest nodal metastasis measured 5 mm or less vs 6% for those with metastases measuring greater than 5 mm. For non-irradiated patients only, regional recurrence rates were 2% and 9%, respectively. Those with a maximal nodal size greater than 5 mm had a significantly higher cumulative incidence of regional recurrence (P=.013). The 5-year cumulative incidence of a regional recurrence in the non-irradiated group was 2.7% (95% confidence interval [CI], 0.7%-7.2%) for maximal metastasis size of 5 mm or less, 6.9% (95% CI, 1.7%-17.3%) for metastasis size greater than 5 mm, and 16% (95% CI, 3.4%-36.8%) for metastasis size greater than 10 mm. The impact of the maximal nodal size on regional recurrences became insignificant in the multivariable model. Conclusions: In patients with 1-3 positive lymph nodes undergoing mastectomy without radiation, nodal metastasis greater than 5 mm was associated with regional recurrence after mastectomy, but its effect was modified by other factors (such as tumor stage). The size of the largest nodal metastasis may be useful to identify high-risk patients who may benefit from radiation therapy after mastectomy.
    International journal of radiation oncology, biology, physics 08/2012; 85(3). DOI:10.1016/j.ijrobp.2012.05.050 · 4.26 Impact Factor
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    ABSTRACT: Purpose: Previously, we developed a radiosensitivity molecular signature [radiosensitivity index (RSI)] that was clinically validated in 3 independent datasets (rectal, esophageal, and head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT)-treated breast cancer patients. Experimental design: RSI was tested in 2 previously published breast cancer datasets. Patients were treated at the Karolinska University Hospital (n = 159) and Erasmus Medical Center (n = 344). RSI was applied as previously described. Results: We tested RSI in RT-treated patients (Karolinska). Patients predicted to be radiosensitive (RS) had an improved 5-year relapse-free survival when compared with radioresistant (RR) patients (95% vs. 75%, P = 0.0212), but there was no difference between RS/RR patients treated without RT (71% vs. 77%, P = 0.6744), consistent with RSI being RT-specific (interaction term RSI × RT, P = 0.05). Similarly, in the Erasmus dataset, RT-treated RS patients had an improved 5-year distant metastasis-free survival over RR patients (77% vs. 64%, P = 0.0409), but no difference was observed in patients treated without RT (RS vs. RR, 80% vs. 81%, P = 0.9425). Multivariable analysis showed RSI is the strongest variable in RT-treated patients (Karolinska, HR = 5.53, P = 0.0987, Erasmus, HR = 1.64, P = 0.0758) and in backward selection (removal α of 0.10), RSI was the only variable remaining in the final model. Finally, RSI is an independent predictor of outcome in RT-treated ER(+) patients (Erasmus, multivariable analysis, HR = 2.64, P = 0.0085). Conclusions: RSI is validated in 2 independent breast cancer datasets totaling 503 patients. Including prior data, RSI is validated in 5 independent cohorts (621 patients) and represents, to our knowledge, the most extensively validated molecular signature in radiation oncology.
    Clinical Cancer Research 07/2012; 18(18):5134-5143. DOI:10.1158/1078-0432.CCR-12-0891 · 8.72 Impact Factor
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    ABSTRACT: Proton beam therapy (PBT) is a novel method for treating malignant disease with radiotherapy. The purpose of this work was to evaluate the state of the science of PBT and arrive at a recommendation for the use of PBT. The emerging technology committee of the American Society of Radiation Oncology (ASTRO) routinely evaluates new modalities in radiotherapy and assesses the published evidence to determine recommendations for the society as a whole. In 2007, a Proton Task Force was assembled to evaluate the state of the art of PBT. This report reflects evidence collected up to November 2009. Data was reviewed for PBT in central nervous system tumors, gastrointestinal malignancies, lung, head and neck, prostate, and pediatric tumors. Current data do not provide sufficient evidence to recommend PBT in lung cancer, head and neck cancer, GI malignancies, and pediatric non-CNS malignancies. In hepatocellular carcinoma and prostate cancer and there is evidence for the efficacy of PBT but no suggestion that it is superior to photon based approaches. In pediatric CNS malignancies PBT appears superior to photon approaches but more data is needed. In large ocular melanomas and chordomas, we believe that there is evidence for a benefit of PBT over photon approaches. PBT is an important new technology in radiotherapy. Current evidence provides a limited indication for PBT. More robust prospective clinical trials are needed to determine the appropriate clinical setting for PBT.
    Radiotherapy and Oncology 03/2012; 103(1):8-11. DOI:10.1016/j.radonc.2012.02.001 · 4.36 Impact Factor
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    ABSTRACT: Purpose: To evaluate the impact of re-excision and the presence of residual disease on local recurrence for patients who underwent breast conservation treatment (BCT) with negative final resection margins. Methods: The records of 902 patients with stage I or II unilateral invasive breast cancer who had BCT were reviewed. The study cohort consisted of patients with negative final resection margins and was divided into 3 subgroups: (a) single excision (n = 332 [37%]), (b) re-excision with no residual disease in the re-excision specimen (n = 440 [49%]), and (c) re-excision with residual disease in the re-excision specimen (n = 130 [14%]). The median follow-up was 6.75 years. Results: At 15 years, the rates of local failure were 10% for patients with a single excision, 10% for patients with a re-excision without residual disease, and 16% for patients with a re-excision with residual disease (P =.033). There were no significant differences between the 3 groups for overall survival, cause-specific survival, relapse-free survival, or freedom from distant metastases (all P <.082). Multivariate analysis demonstrated an increased risk of local failure for patients with residual disease in the re-excision specimen that was borderline statistically significant (hazard ratio, 2.16; P =.061). Conclusions: Despite achieving negative final resection margins, the patients with residual disease in the re-excision specimen had a higher rate of local recurrence than patients who underwent single excision or patients without residual disease on re-excision. However, local recurrence was reasonably low in all 3 subgroups, and, therefore, neither re-excision nor residual disease represent contraindications for BCT.
    Clinical Breast Cancer 12/2011; 11(6):400-5. DOI:10.1016/j.clbc.2011.08.003 · 2.11 Impact Factor
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    Sophia M Edwards-Bennett · Candace R Correa · Eleanor E Harris ·
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    ABSTRACT: Adjuvant breast radiation therapy after breast conservation surgery is recommended as it yields significant reduction in the risk of local recurrence, and confers a potential overall survival benefit. Although the standard breast radiation regimen has historically been delivered over 5-7 weeks; more novel, shorter courses of breast radiation are currently being employed, offering the advantage of more convenience and less time-commitment. Herein, we review the recent literature substantiating these abbreviated radiation treatment approaches and the methods of delivery thereof. In addition, we discuss imaged guided techniques currently being utilized to further refine the delivery of adjuvant breast radiation therapy.
    10/2011; 2011:321304. DOI:10.4061/2011/321304

  • Fuel and Energy Abstracts 10/2011; 81(2). DOI:10.1016/j.ijrobp.2011.06.125
  • S. M. Edwards-Bennett · C. R. Correa · W. Li · E. E. Harris ·

    Fuel and Energy Abstracts 10/2011; 81(2). DOI:10.1016/j.ijrobp.2011.06.460
  • D. Opp · H. Chotaliya · W. Li · K. Forster · E. Harris ·

    Fuel and Energy Abstracts 10/2011; 81(2). DOI:10.1016/j.ijrobp.2011.06.1731
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    ABSTRACT: National Comprehensive Cancer Network (NCCN) guidelines for female breast cancer treatment and surveillance are well established, but similar guidelines on male breast cancers are less recognized. As an NCCN institution, our objective was to examine practice patterns and follow-up for male breast cancer compared to established guidelines for female patients. After Institutional Review Board approval, a prospective breast database from 1990 to 2009 was queried for male patients. Medical records were examined for clinico-pathological factors and follow-up. The 5-year survival rates with 95% confidence intervals were estimated using Kaplan-Meier method and Greenwood formula. Of the 19,084 patients in the database, 73 (0.4%) were male patients; 62 had complete data. One patient had bilateral synchronous breast cancer. The median age was 68.8 years (range 29-85 years). The mean/median invasive tumor size was 2.2/1.6 cm (range 0.0-10.0 cm). All cases had mastectomy (29 with axillary node dissection, 23 with sentinel lymph node biopsy only, 11 with sentinel node biopsy followed by completion axillary dissection). Lymph node involvement occurred in 25/63 (39.7%). Based on NCCN guidelines, chemotherapy, hormonal therapy, and radiation are indicated in 34 cases, 62 cases, and 14 cases, respectively. Only 20/34 (59%) received chemotherapy, 51/62 (82%) received hormonal therapy, and 10/14 (71%) received post-mastectomy radiation. Median follow-up was 26.2 months (range: 1.6-230.9 months). The 5-year survival estimates for node positive and negative diseases were 68.5% and 87.5%, respectively (p = 0.3). Despite the rarity of male breast cancer, treatment options based on current female breast tumors produce comparable results to female breast cancer. Increased awareness and a national registry for patients could help improve outcomes and tailor treatment recommendations to the male variant.
    The Breast Journal 09/2011; 17(5):503-9. DOI:10.1111/j.1524-4741.2011.01148.x · 1.41 Impact Factor
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    ABSTRACT: To detect the molecular changes of malignancy in histologically normal breast (HNB) tissues, we recently developed a novel 117-gene-malignancy-signature. Here we report validation of our leading malignancy-risk-genes, topoisomerase-2-alpha (TOP2A), minichromosome-maintenance-protein-2 (MCM2) and "budding-uninhibited-by-benzimidazoles-1-homolog-beta" (BUB1B) at the protein level. Using our 117-gene malignancy-signature, we classified 18 fresh-frozen HNB tissues from 18 adult female breast cancer patients into HNB-tissues with low-grade (HNB-LGMA; N = 9) and high-grade molecular abnormality (HNB-HGMA; N = 9). Archival sections of additional HNB tissues from these patients, and invasive ductal carcinoma (IDC) tissues from six other patients were immunostained for these biomarkers. TOP2A/MCM2 expression was assessed as staining index (%) and BUB1B expression as H-scores (0-300). Increasing TOP2A, MCM2, and BUB1B protein expression from HNB-LGMA to HNB-HGMA tissues to IDCs validated our microarray-based molecular classification of HNB tissues by immunohistochemistry. We also demonstrated an increasing expression of TOP2A protein on an independent test set of HNB/benign/reductionmammoplasties, atypical-ductal-hyperplasia with and without synchronous breast cancer, DCIS and IDC tissues using a custom tissue microarray (TMA). In conclusion, TOP2A, MCM2, and BUB1B proteins are potential molecular biomarkers of malignancy in histologically normal and benign breast tissues. Larger-scale clinical validation studies are needed to further evaluate the clinical utility of these molecular biomarkers.
    Pathology Research International 07/2011; 2011:489064. DOI:10.4061/2011/489064
  • E. Harris · J. Prtiz · K. Latifi · G. Zhang · K. Forster ·

    Radiotherapy and Oncology 05/2011; 99. DOI:10.1016/S0167-8140(11)70880-5 · 4.36 Impact Factor
  • R.R. Zhang · G.G. Zhang · E. Harris · K. Forster · V. Feygelman ·
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    ABSTRACT: When Monte Carlo (MC) method is used for dose calculations on a patient CT dataset, the materials in the CT images are often assigned based on the local Houndsfield units if the density threshold method is applied. In bolus electron conformal therapy (bolusECT), the bolus material, machinable wax, is therefore treated as soft tissue. This study investigates the dose errors introduced by this material misassignment. BEAMnrc was used to simulate electron beams from a Varian Trilogy accelerator. SPRRZnrc code was used to calculate stopping power ratios of tissue to wax, , and tissue to water, , for 12 and 15 MeV electron beams. DOSXYZnrc was applied to calculate dose in a tissue phantom with the rectangular wax slabs of various thicknesses or a wedge-shaped bolus on top. The values for 12 and 15 MeV beams were calculated to be 0.935~0.945, while the values were 0.990~0.991. The dose in tissue immediately under the bolus is overestimated by about 2.5% of maximum dose with the 3 cm bolus thickness if wax bolus is treated as tissue for 12 MeV beams. For 15 MeV beams, the error is about 1.4%. A left chest wall electron treatment case was simulated using wax and soft tissue as bolus materials in turn. Dose differences are observed in MC simulations if the bolus material is misassigned as tissue in bolusECT dose calculations. However, the error is mostly within clinical tolerance, especially for thin bolus regions which are more likely to be encountered in practice.
    Medical Physics 01/2011; 38(6):3648-. DOI:10.1118/1.3612648 · 2.64 Impact Factor

  • The American surgeon 01/2011; 77(1):E10-2. · 0.82 Impact Factor
  • D. K. Arora · J. Freilich · J. Scott · D. Opp · C. Johnson · E. Harris ·

    Fuel and Energy Abstracts 11/2010; 78(3). DOI:10.1016/j.ijrobp.2010.07.534
  • D. Opp · K. Forster · W. Li · E. Harris ·

    Fuel and Energy Abstracts 11/2010; 78(3). DOI:10.1016/j.ijrobp.2010.07.1912

Publication Stats

1k Citations
237.84 Total Impact Points


  • 2014-2015
    • East Carolina University
      Гринвилл, North Carolina, United States
  • 2009-2013
    • Moffitt Cancer Center
      • • Department of Biostatistics
      • • Department of Radiation Oncology
      Tampa, Florida, United States
  • 2008-2012
    • University of South Florida
      Tampa, Florida, United States
  • 2000-2011
    • University of Pennsylvania
      • Department of Radiation Oncology
      Philadelphia, Pennsylvania, United States
  • 2002-2007
    • Hospital of the University of Pennsylvania
      • Department of Radiation Oncology
      Philadelphia, Pennsylvania, United States
  • 2006
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2005-2006
    • William Penn University
      Filadelfia, Pennsylvania, United States