Publications by authors named "Kevin Pearlstein"

16 Publications

  • Page 1 of 1

Coronary Artery Calcifications and Cardiac Risk After Radiation Therapy for Stage III Lung Cancer.

Int J Radiat Oncol Biol Phys 2021 Aug 19. Epub 2021 Aug 19.

Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina.

Purpose: Heart dose and heart disease increase the risk for cardiac toxicity associated with radiation therapy. We hypothesized that computed tomography (CT) coronary calcifications are associated with cardiac toxicity and may help ascertain baseline heart disease.

Methods And Materials: We analyzed the cumulative incidence of cardiac events in patients with stage III non-small cell lung cancer receiving median 74 Gy on prospective dose-escalation trials. Events were defined as symptomatic effusion, pericarditis, unstable angina, infarction, significant arrhythmia, and/or heart failure. Coronary calcifications were delineated on simulation CTs using radiation software program (130 HU threshold). Calcifications were defined as "none," "low," and "high," with median volume dividing low and high.

Results: Of 109 patients, 26 had cardiac events at median 26 months (range, 1-84 months) after radiation therapy. Median follow-up in surviving patients was 8.8 years (range, 2.3-17.3). On simulation CTs, 64 patients (59%) had coronary calcifications with median volume 0.2 cm (range, 0.01-8.3). Only 16 patients (15%) had baseline coronary artery disease. Cardiac events occurred in 7% (3 of 45), 29% (9 of 31), and 42% (14 of 33) of patients with no, low, and high calcifications, respectively. Calcification burden was associated with cardiac toxicity on univariate (low vs none: hazard ratio [HR] 5.0, P = .015; high vs none: HR 8.1, P < .001) and multivariate analyses (low vs none: HR 7.0, P = .005, high vs none: HR 10.6, P < .001, heart mean dose: HR 1.1/Gy, P < .001). Four-year competing risk-adjusted event rates for no, low, and high calcifications were 4%, 23%, and 34%, respectively.

Conclusions: The presence of coronary calcifications is a cardiac risk factor that can identify high-risk patients for medical referral and help guide clinicians before potentially cardiotoxic cancer treatments.
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http://dx.doi.org/10.1016/j.ijrobp.2021.08.017DOI Listing
August 2021

NTCP modeling and dose-volume correlations for acute xerostomia and dry eye after whole brain radiation.

Radiat Oncol 2021 Mar 21;16(1):56. Epub 2021 Mar 21.

Department of Radiation Oncology, University of North Carolina, 101 Manning Dr., Chapel Hill, NC, 27599-7512, USA.

Background: Whole brain radiation (WBRT) may lead to acute xerostomia and dry eye from incidental parotid and lacrimal exposure, respectively. We performed a prospective observational study to assess the incidence/severity of this toxicity. We herein perform a secondary analysis relating parotid and lacrimal dosimetric parameters to normal tissue complication probability (NTCP) rates and associated models.

Methods: Patients received WBRT to 25-40 Gy in 10-20 fractions using 3D-conformal radiation therapy without prospective delineation of the parotids or lacrimals. Patients completed questionnaires at baseline and 1 month post-WBRT. Xerostomia was assessed using the University of Michigan xerostomia score (scored 0-100, toxicity defined as ≥ 20 pt increase) and xerostomia bother score (scored from 0 to 3, toxicity defined as ≥ 2 pt increase). Dry eye was assessed using the Subjective Evaluation of Symptom of Dryness (SESoD, scored from 0 to 4, toxicity defined as ≥ 2 pt increase). The clinical data were fitted by the Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) NTCP models.

Results: Of 55 evaluable patients, 19 (35%) had ≥ 20 point increase in xerostomia score, 11 (20%) had ≥ 2 point increase in xerostomia bother score, and 13 (24%) had ≥ 2 point increase in SESoD score. For xerostomia, parotid V-V correlated best with toxicity, with AUC 0.68 for xerostomia score and 0.69-0.71 for bother score. The values for the D, m and n parameters of the LKB model were 22.3 Gy, 0.84 and 1.0 for xerostomia score and 28.4 Gy, 0.55 and 1.0 for bother score, respectively. The corresponding values for the D, γ and s parameters of the RS model were 23.5 Gy, 0.28 and 0.0001 for xerostomia score and 32.0 Gy, 0.45 and 0.0001 for bother score, respectively. For dry eye, lacrimal V-V were found to correlate best with toxicity, with AUC values from 0.67 to 0.68. The parameter values of the LKB model were 53.5 Gy, 0.74 and 1.0, whereas of the RS model were 54.0 Gy, 0.37 and 0.0001, respectively.

Conclusions: Xerostomia was most associated with parotid V-V, and dry eye with lacrimal V-V. NTCP models were successfully created for both toxicities and may help clinicians refine dosimetric goals and assess levels of risk in patients receiving palliative WBRT.
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http://dx.doi.org/10.1186/s13014-021-01786-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981795PMC
March 2021

The impact of pathologic staging of the hilar/mediastinal nodes on outcomes in patients with early-stage NSCLC receiving stereotactic body radiotherapy.

J Thorac Dis 2021 Feb;13(2):1045-1054

Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, NC, USA.

Background: The importance of invasive mediastinal nodal staging in early-stage non-small cell lung cancer (NSCLC) in the PET/CT era is dependent on tumor factors that increase risk of nodal metastasis. At our institution, patients undergo biopsy via either CT-guidance (without nodal staging) or navigational bronchoscopy with endobronchial ultrasound transbronchial needle aspiration for nodal staging. This study aims to compare outcomes after stereotactic body radiotherapy (SBRT) stratified by receipt of invasive mediastinal nodal staging.

Methods: In this retrospective study, records of all consecutive patients undergoing SBRT for early-stage NSCLC between 2010 and 2017 were analyzed. The association between time-to event outcomes (recurrence and survival) were evaluated with covariates of interest including tumor size, location, histology, smoking history, prior lung cancer history, radiation dose and receipt of nodal staging. Both univariable and multivariable analyses were used to examine these comparisons.

Results: Overall, 158 patients were treated with SBRT. One hundred forty-nine out of one hundred fifty-eight patients (94%) underwent PET/CT staging, and all patients underwent tumor-directed biopsy. Seventy-nine patients underwent navigational bronchoscopy with nodal staging and 79 patients underwent CT-guided biopsy without nodal staging. Receipt of nodal staging was not associated with tumor size (P=0.35), yet was associated with central tumor location (P<0.001). There was no statistically significant association between receipt of nodal staging and time-to-event recurrence or survival outcomes; for example 3-year overall survival (OS) was 65% 67% (P=0.65) and 3-year freedom from nodal failure was 84% 69% (P=0.1) for those with and without nodal staging, respectively.

Conclusions: Similar recurrence and survival outcomes were observed after SBRT regardless of receipt of invasive mediastinal nodal staging. Further prospective evaluation can help identify which patients might derive greatest benefit from invasive staging of the mediastinum in the PET/CT era.
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http://dx.doi.org/10.21037/jtd-20-2808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947488PMC
February 2021

Cardiovascular Care Among Cancer Survivors in the United States.

JNCI Cancer Spectr 2018 Oct 7;2(4):pky049. Epub 2018 Dec 7.

Department of Radiation Oncology.

Background: Cardiovascular disease (CVD) is a leading cause of mortality among cancer survivors, but whether survivors receive routine cardiovascular monitoring and preventive care has not been well studied. This study uses a population-based dataset to examine this question.

Methods: Data from the National Health Interview Survey were used to identify 13 266 cancer survivors who completed surveys from 2011 to 2015. Prevalence of CVD and associated risk factors, patterns of doctor visitation, and receipt of CVD preventive care were examined. We used multivariable logistic regression analysis to examine factors associated with the receipt of preventive care for survivors with and without CVD risk factors.

Results: CVD risk factors were prevalent in older cancer survivors 65 years and older (56.9% with hyperlipidemia, 66.8% with hypertension) and younger survivors younger than 50 years (35.4% obese, 30.3% current smokers). Rates of blood pressure, cholesterol, and glucose monitoring were high, but rates of lifestyle modification were lower (54.8% moderate exercise, 47.1% smoking cessation attempts among smokers). Although 71.5% of survivors at 2 years or less from diagnosis saw both general and specialist doctors, only 51.6% of survivors at 5 or more years saw both, and 43.5% saw only a general doctor. On multivariable analysis, receipt of CVD preventive care was strongly associated with general doctor visitation for those with and without CVD risk factors.

Conclusions: CVD and associated risk factors are prevalent among both older and younger cancer survivors across the United States. This study identifies areas for improvement related to lifestyle modification in survivors, and also highlights the importance of care transition to the primary care provider for long-term survivors.
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http://dx.doi.org/10.1093/jncics/pky049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649739PMC
October 2018

Prospective Assessment of Patient-Reported Dry Eye Syndrome After Whole Brain Radiation.

Int J Radiat Oncol Biol Phys 2019 11 24;105(4):765-772. Epub 2019 Jul 24.

Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, North Carolina.

Purpose: Dry eye is not typically considered a toxicity of whole brain radiation therapy (WBRT). We analyzed dry eye syndrome as part of a prospective study of patient-reported outcomes after WBRT.

Methods And Materials: Patients receiving WBRT to 25 to 40 Gy were enrolled on a study with dry mouth as the primary endpoint and dry eye syndrome as a secondary endpoint. Patients received 3-dimensional WBRT using opposed lateral fields. Per standard practice, lacrimal glands were not prospectively delineated. Patients completed the Subjective Evaluation of Symptom of Dryness (SESoD, scored 0-4, with higher scores representing worse dry eye symptoms) at baseline, immediately after WBRT (EndRT), and at 1 month (1M), 3 months, and 6 months. Patients with baseline SESoD ≥3 (moderate dry eye) were excluded. The endpoints analyzed were ≥1-point and ≥2-point increase in SESoD score at 1M. Lacrimal glands were retrospectively delineated with fused magnetic resonance imaging scans.

Results: One hundred patients were enrolled, 70 were eligible for analysis, and 54 were evaluable at 1M. Median bilateral lacrimal V20Gy was 79%. At 1M, 17 patients (32%) had a ≥1-point increase in SESoD score, and 13 (24%) a ≥2-point increase. Lacrimal doses appeared to be associated with an increase in SESoD score of both ≥1 point (V10Gy: P = .042, odds ratio [OR] 1.09/%; V20Gy: P = .071, OR 1.03/%) and ≥2 points (V10Gy: P = .038, OR 1.15/%; V20Gy: P = .063, OR 1.04/%). The proportion with increase in dry eye symptoms at 1M for lacrimal V20Gy ≥79% versus <79% was 46% versus 15%, respectively, for ≥1 point SESoD increase (P = .02) and 36% versus 12%, respectively, for ≥2 point SESoD increase (P = .056).

Conclusions: Dry eye appears to be a relatively common, dose/volume-dependent acute toxicity of WBRT. Minimization of lacrimal gland dose may reduce this toxicity, and patients should be counseled regarding the existence of this potential side effect and treatments for dry eye.
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http://dx.doi.org/10.1016/j.ijrobp.2019.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384248PMC
November 2019

Assessment of Risk of Xerostomia After Whole-Brain Radiation Therapy and Association With Parotid Dose.

JAMA Oncol 2019 02;5(2):221-228

Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill.

Importance: Whole-brain radiation therapy (WBRT) delivers a substantial radiation dose to the parotid glands, but the parotid glands are not delineated for avoidance and xerostomia has never been reported as an adverse effect. Minimizing the toxic effects in patients receiving palliative treatments, such as WBRT, is crucial.

Objective: To assess whether xerostomia is a toxic effect of WBRT.

Design, Setting, And Participants: This observational cohort study enrolled patients from November 2, 2015, to March 20, 2018, at 1 academic center (University of North Carolina Hospitals) and 2 affiliated community hospitals (High Point Regional Hospital and University of North Carolina Rex Hospital). Adult patients (n = 100) receiving WBRT for the treatment or prophylaxis of brain metastases were enrolled. Patients who had substantial baseline xerostomia or did not complete WBRT or at least 1 postbaseline questionnaire were prospectively excluded from analysis and follow-up. Patients received 3-dimensional WBRT using opposed lateral fields covering the skull and the C1 or C2 vertebra. Per standard practice, the parotid glands were not prospectively delineated.

Main Outcomes And Measures: Patients completed the University of Michigan Xerostomia Questionnaire and a 4-point bother score at baseline, immediately after WBRT, at 1 month, at 3 months, and at 6 months. The primary end point was the 1-month xerostomia score, with a hypothesized worsening score of 10 points from baseline.

Results: Of the 100 patients enrolled, 73 (73%) were eligible for analysis and 55 (55%) were evaluable at 1 month. The 73 patients included 43 women (59%) and 30 men (41%) with a median (range) age of 61 (23-88) years. The median volume of parotid receiving at least 20 Gy (V20Gy) was 47%. The mean xerostomia score was 7 points at baseline and was statistically significantly higher at each assessment period, including 21 points immediately after WBRT (95% CI, 16-26; P < .001), 23 points (95% CI, 16-30; P < .001) at 1 month, 21 points (95% CI, 13-28; P < .001) at 3 months, and 14 points (95% CI, 7-21; P = .03) at 6 months. At 1 month, the xerostomia score increased by 20 points or more in 19 patients (35%). The xerostomia score at 1 month was associated with parotid dose as a continuous variable and was 35 points in patients with parotid V20Gy of 47% or greater, compared with only 9 points in patients with parotid V20Gy less than 47% (P < .001). The proportion of patients who self-reported to be bothered quite a bit or bothered very much by xerostomia at 1 month was 50% in those with parotid V20Gy of 47% or greater, compared with only 4% in those with parotid V20Gy less than 47% (P < .001). At 3 months, this difference was 50% vs 0% (P = .001). Xerostomia was not associated with medication use.

Conclusions And Relevance: Clinically significant xerostomia occurred by the end of WBRT, appeared to be persistent, and appeared to be associated with parotid dose. The findings from this study suggest that the parotid glands should be delineated for avoidance to minimize these toxic effects in patients who undergo WBRT and often do not survive long enough for salivary recovery.
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http://dx.doi.org/10.1001/jamaoncol.2018.4951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439567PMC
February 2019

Quality of Life for Patients With Favorable-Risk HPV-Associated Oropharyngeal Cancer After De-intensified Chemoradiotherapy.

Int J Radiat Oncol Biol Phys 2019 03 2;103(3):646-653. Epub 2018 Nov 2.

Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; UNC Lineberger Comprehensive Cancer Center, University of North Carolina Hospitals, Chapel Hill, North Carolina. Electronic address:

Purpose: Oropharynx cancers associated with human papillomavirus (HPV) have a favorable prognosis, but current treatment approaches carry significant long-term morbidity. Strategies to de-intensify treatment in this population are under investigation, but the impact of these approaches on quality of life (QOL) is not well understood. We present patient-reported outcomes from 2 prospective studies examining de-intensified chemoradiotherapy.

Methods And Materials: This study included patients enrolled in 2 prospective phase 2 trials of de-intensified chemoradiotherapy in patients with HPV-associated oropharynx cancer who had at least 1 year of follow-up. Treatment included concurrent radiation therapy (60 Gy) and chemotherapy (weekly cisplatin, 30 mg/m). Patients reported QOL and symptoms using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module-35, and the Eating Assessment Tool-10 instruments before treatment and at regular intervals thereafter. Changes in QOL and individual symptoms were examined over time, and multivariate analysis was used to identify clinical factors associated with recovery to baseline symptom levels.

Results: Of the 154 patients enrolled, 126 patients had at least 1 year of follow-up and were included in this study (median follow-up, 25 months). Global QOL, functional indices, and most individual symptoms returned to baseline 3 to 6 months after treatment. Swallowing (Eating Assessment Tool-10 score) returned to baseline function by 2 years, but dry mouth, sticky saliva, and taste/senses did not return to baseline levels. However, from 1 to 2 years, continued improvement occurred in dry mouth score (55 vs 48), sticky saliva score (35 vs 27), and senses score (24 vs 20). On multivariate analysis, unilateral radiation therapy was associated with returning to baseline level of swallowing and sticky saliva.

Conclusions: The use of de-intensified chemoradiotherapy in HPV-associated oropharynx cancer led to favorable patient-reported outcomes, with early recovery of QOL and continued improvement of xerostomia and dysphagia beyond 1-year posttreatment.
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http://dx.doi.org/10.1016/j.ijrobp.2018.10.033DOI Listing
March 2019

Comparative Effectiveness of Prostate Cancer Treatment Options: Limitations of Retrospective Analysis of Cancer Registry Data.

Int J Radiat Oncol Biol Phys 2019 04 9;103(5):1053-1057. Epub 2018 Aug 9.

Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address:

Purpose: Retrospective analyses of cancer registry and institutional data have consistently found better survival after radical prostatectomy versus radiation therapy, which contrasts with findings from a randomized trial. This is likely because of the inability of retrospective studies to fully account for comorbidity differences across treatment groups because of the lack of detailed data in the registries. We use a unique population-based data set with detailed data regarding comorbidities and functional limitations to assess whether this can provide valid comparisons of survival across prostate cancer treatment groups.

Methods And Materials: The Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) data set results from a linkage between the SEER database and the MHOS database, which includes detailed information regarding patient-reported comorbidity and functional limitations. We analyzed 3102 patients with prostate cancer in SEER-MHOS and used latent class analysis to identify the healthiest group with minimal comorbidity burden and functional limitations. Among the healthiest group, we examined overall survival across treatments using the Kaplan-Meier method.

Results: Three distinct health groups were identified using latent class analysis; the healthiest group comprised 57% of the cohort and had a 10-year overall survival of 67%. Other health groups had higher rates of comorbidities or functional limitations. Among the healthiest group, 10-year overall survival differed across treatment groups: no local treatment (55%), external beam radiation therapy (69%), brachytherapy (76%), and radical prostatectomy (85%). Survival curves for the 3 treated groups separated at 4 years of follow-up.

Conclusions: Despite the detailed health status information available in SEER-MHOS, our retrospective analysis could not fully account for patient selection biases across prostate cancer treatment groups. These findings highlight an important limitation of retrospective studies using population-based data sets and serve as a reminder to interpret results with caution.
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http://dx.doi.org/10.1016/j.ijrobp.2018.08.001DOI Listing
April 2019

Paraneoplastic psoriasis in a patient with prostate cancer.

JAAD Case Rep 2018 Apr 23;4(3):220-221. Epub 2018 Feb 23.

Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina.

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http://dx.doi.org/10.1016/j.jdcr.2017.09.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909472PMC
April 2018

Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy.

Radiat Oncol 2018 Feb 2;13(1):17. Epub 2018 Feb 2.

Department of Radiation Oncology, University of North Carolina, 101 Manning Dr, Chapel Hill, NC, 27599-7512, USA.

Background: To estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms.

Methods: Ninety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study. Patient-reported urinary symptoms were collected pre-RT and weekly during treatment using the validated Prostate Cancer Symptom Indices (PCSI). The assessed symptoms were flow, dysuria, urgency, incontinence, frequency and nocturia using a Likert scale of 1 to 4 or 5. For this analysis, an increase by ≥2 levels in a symptom at any time during treatment compared to baseline was considered clinically significant. The dose volume histograms of the bladder were calculated. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS) and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC) and Odds Ratio methods.

Results: For the symptoms of urinary urgency, leakage, frequency and nocturia, the derived LKB model parameters were: 1) D = 64.2Gy, m = 0.50, n = 1.0; 2) D = 95.0Gy, m = 0.45, n = 0.50; 3) D = 83.1Gy, m = 0.56, n = 1.00; and 4) D = 85.4Gy, m = 0.60, n = 1.00, respectively. The AUC values for those symptoms were 0.66, 0.58, 0.64 and 0.64, respectively. The differences in AIC between the different models were less than 2 and ranged within 0.1 and 1.3.

Conclusions: Different dose metrics were correlated with the symptoms of urgency, incontinence, frequency and nocturia. The symptoms of urinary flow and dysuria were poorly associated with dose. The values of the parameters of three NTCP models were determined for bladder regarding four acute urinary symptoms. All the models could fit the clinical data equally well. The NTCP predictions of urgency showed the best correlation with the patient reported outcomes.
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http://dx.doi.org/10.1186/s13014-018-0961-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797360PMC
February 2018

Heart dosimetric analysis of three types of cardiac toxicity in patients treated on dose-escalation trials for Stage III non-small-cell lung cancer.

Radiother Oncol 2017 11 16;125(2):293-300. Epub 2017 Oct 16.

Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, United States.

Background And Purpose: To assess associations between radiation dose/volume parameters for cardiac subvolumes and different types of cardiac events in patients treated on radiation dose-escalation trials.

Material And Methods: Patients with Stage III non-small-cell lung cancer received dose-escalated radiation (median 74 Gy) using 3D-conformal radiotherapy on six prospective trials from 1996 to 2009. Volumes analyzed included whole heart, left ventricle (LV), right atrium (RA), and left atrium (LA). Cardiac events were divided into three categories: pericardial (symptomatic effusion and pericarditis), ischemia (myocardial infarction and unstable angina), and arrhythmia. Univariable competing risks analysis was used.

Results: 112 patients were analyzed, with median follow-up 8.8 years for surviving patients. Nine patients had pericardial, seven patients had ischemic, and 12 patients had arrhythmic events. Pericardial events were correlated with whole heart, RA, and LA dose (eg, heart-V30 [p=0.024], RA-V30 [p=0.013], and LA-V30 [p=0.001]), but not LV dose. Ischemic events were correlated with LV and whole heart dose (eg, LV-V30 [p=0.012], heart-V30 [p=0.048]). Arrhythmic events showed borderline significant associations with RA, LA, and whole heart dose (eg, RA-V30 [p=0.082], LA-V30 [p=0.076], heart-V30 [p=0.051]). Cardiac events were associated with decreased survival on univariable analysis (p=0.008, HR 2.09), but only disease progression predicted for decreased survival on multivariable analysis.

Conclusions: Cardiac events were heterogeneous and associated with distinct heart subvolume doses. These data support the hypothesis of distinct etiologies for different types of radiation-associated cardiotoxicity.
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http://dx.doi.org/10.1016/j.radonc.2017.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705468PMC
November 2017

Patient-reported quality of life during definitive and postprostatectomy image-guided radiation therapy for prostate cancer.

Pract Radiat Oncol 2017 Mar - Apr;7(2):e117-e124. Epub 2016 Aug 12.

Department of Radiation Oncology, University of North Carolina at Chapel Hill, North Carolina; Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina. Electronic address:

Purpose: The importance of patient-reported outcomes is well-recognized. Long-term patient-reported symptoms have been described for individuals who completed radiation therapy (RT) for prostate cancer. However, the trajectory of symptom development during the course of treatment has not been well-described in patients receiving modern, image-guided RT.

Methods And Materials: Quality-of-life data were prospectively collected for 111 prostate cancer patients undergoing RT using the validated Prostate Cancer Symptom Indices, which assessed 5 urinary obstructive/irritative and 6 bowel symptoms. Patients who received definitive RT (N = 73) and postprostatectomy RT (N = 38) were analyzed separately. The frequency and severity of symptoms over multiple time points are reported.

Results: An increasing number of patients had clinically meaningful urinary and bowel symptoms over the course of RT. A greater proportion of patients undergoing definitive RT reported clinically meaningful urinary symptoms at the end of RT compared with baseline in terms of flow (33% vs 19%) and frequency (39% vs 18%). Individuals receiving postprostatectomy radiation also reported an increase in symptoms including frequency (29% vs 3%) and nocturia (50% vs 21%). Clinically meaningful bowel symptoms were less commonly reported. Patients receiving definitive RT reported an increase in diarrhea (9% vs 4%) and urgency (12% vs 6%) at the completion of RT compared with baseline. Both bowel and urinary symptoms approached their baseline levels by the time of first follow-up after treatment completion. The majority of patients who had clinically meaningful urinary or bowel symptoms during RT did not have them at 2 years or beyond, and development of new symptoms in the long term was uncommon.

Conclusions: There is a modest increase in urinary and bowel symptoms over the course of treatment for individuals receiving definitive and postprostatectomy image-guided RT. These data can help inform both providers and patients regarding the trajectory of symptoms and allow for reasonable expectations regarding toxicity under treatment.
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http://dx.doi.org/10.1016/j.prro.2016.08.004DOI Listing
March 2017

Comparison of Patient Report and Medical Records of Comorbidities: Results From a Population-Based Cohort of Patients With Prostate Cancer.

JAMA Oncol 2017 Aug;3(8):1035-1042

Department of Radiation Oncology, the University of North Carolina at Chapel Hill, Chapel Hill.

Importance: The comorbid conditions of patients with cancer affect treatment decisions, which in turn affect survival and health-related quality-of-life outcomes. Comparative effectiveness research studies must account for these conditions via medical record abstraction or patient report.

Objective: To examine the agreement between medical records and patient reports in assessing comorbidities.

Design, Setting, And Participants: Patient-reported information and medical records were prospectively collected as part of the North Carolina Prostate Cancer Comparative Effectiveness & Survivorship Study, a population-based cohort of 881 patients with newly diagnosed localized prostate cancer enrolled in the North Carolina Central Cancer Registry from January 1, 2011, through June 30, 2013. The presence or absence of 20 medical conditions was compared based on patient report vs abstraction of medical records.

Main Outcomes And Measures: Agreement between patient reports and medical records for each condition was assessed using the κ statistic. Subgroup analyses examined differences in κ statistics based on age, race, marital status, educational level, and income. Logistic regression models for each condition examined factors associated with higher agreement.

Results: A total of 881 patients participated in the study (median age, 65 years; age range, 41-80 years; 633 white [71.9%]). In 16 of 20 conditions, there was agreement between patient reports and medical records for more than 90% of patients; agreement was lowest for hyperlipidemia (68%; κ = 0.36) and arthritis (66%; κ = 0.14). On multivariable analysis, older age (≥70 years old) was significantly associated with lower agreement for myocardial infarction (odds ratio [OR], 0.31; 95% CI, 0.12-0.80), cerebrovascular disease (OR, 0.10; 95% CI, 0.01-0.78), coronary artery disease (OR, 0.37; 95% CI, 0.20-0.67), arrhythmia (OR, 0.44; 95% CI, 0.25-0.79), and kidney disease (OR, 0.18; 95% CI, 0.06-0.52). Race and educational level were not significantly associated with κ in 18 of 19 modeled conditions.

Conclusions And Relevance: Overall, patient reporting provides information similar to medical record abstraction without significant differences by patient race or educational level. Use of patient reports, which are less costly than medical record audits, is a reasonable approach for observational comparative effectiveness research.
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http://dx.doi.org/10.1001/jamaoncol.2016.6744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824220PMC
August 2017

Comparing dosimetric, morbidity, quality of life, and cancer control outcomes after 3D conformal, intensity-modulated, and proton radiation therapy for prostate cancer.

Semin Radiat Oncol 2013 Jul;23(3):182-90

Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

New radiation technologies have been developed and adopted for clinical use in prostate cancer treatment in response to a need to deliver dose-escalated radiation therapy while minimizing treatment-related morbidity. The goal of this article is to examine the currently available evidence comparing dosimetric and patient outcomes of newer versus older radiation technologies in prostate cancer. Overall, although a body of dosimetry studies have demonstrated the ability of newer versus older technologies (intensity-modulated radiation therapy vs 3-dimensional conformal radiation therapy; proton vs intensity-modulated radiation therapy) to reduce radiation doses delivered to the rectum and bladder, more studies are needed to demonstrate that these dosimetric benefits translate into improved patient outcomes.
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http://dx.doi.org/10.1016/j.semradonc.2013.01.004DOI Listing
July 2013

Population genetic inference from personal genome data: impact of ancestry and admixture on human genomic variation.

Am J Hum Genet 2012 Oct;91(4):660-71

Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.

Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas-70% of the European ancestry in today's African Americans dates back to European gene flow happening only 7-8 generations ago.
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http://dx.doi.org/10.1016/j.ajhg.2012.08.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484644PMC
October 2012

Infrared imaging of trauma patients for detection of acute compartment syndrome of the leg.

Crit Care Med 2008 Jun;36(6):1756-61

University of North Carolina at Chapel Hill, Department of Emergency Medicine, Chapel Hill, North Carolina 27599, USA.

Objective: Early compartment syndrome is difficult to diagnose, and a delay in the diagnosis can result in amputation or death. Our objective was to explore the potential of infrared imaging, a portable and noninvasive technology, for detecting compartment syndrome in the legs of patients with multiple trauma. We hypothesized that development of compartment syndrome is associated with a reduction in surface temperature in the involved leg and that the temperature reduction can be detected by infrared imaging.

Design: Observational clinical study.

Setting: Level I trauma center between July 2006 and July 2007.

Patients: Trauma patients presenting to the emergency department.

Interventions: Average temperature of the anterior surface of the proximal and distal region of each leg was measured in the emergency department with a radiometrically calibrated, 320 x 240, uncooled microbolometer infrared camera.

Measurements And Main Results: The difference in surface temperature between the thigh and foot regions (thigh-foot index) of the legs in trauma patients was determined by investigators blinded to injury pattern using thermographic image analysis software. The diagnosis of compartment syndrome was made intraoperatively. Thermographic images from 164 patients were analyzed. Eleven patients developed compartment syndrome, and four of those patients had bilateral compartment syndrome. Legs that developed compartment syndrome had a greater difference in proximal vs. distal surface temperature (8.80 +/- 2.05 degrees C) vs. legs without compartment syndrome (1.22 +/- 0.88 degrees C) (analysis of variance p < .01). Patients who developed unilateral compartment syndrome had a greater proximal vs. distal temperature difference in the leg with (8.57 +/- 2.37 degrees C) vs. the contralateral leg without (1.80 +/- 1.60 degrees C) development of compartment syndrome (analysis of variance p < .01).

Conclusions: Infrared imaging detected a difference in surface temperature between the proximal and distal leg of patients who developed compartment syndrome. This technology holds promise as a supportive tool for the early detection of acute compartment syndrome in trauma patients.
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http://dx.doi.org/10.1097/CCM.0b013e318174d800DOI Listing
June 2008
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