Christopher R Kelsey

Duke University, Durham, North Carolina, United States

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Publications (15)57.55 Total impact

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    ABSTRACT: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective identification of risk factors for local recurrence may aid in selecting an appropriate population for further study of postoperative radiation therapy. Copyright © 2015 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 03/2015; 91(4). DOI:10.1016/j.ijrobp.2014.12.028 · 4.26 Impact Factor
  • Lulin Yuan · Q Jackie Wu · Fangfang Yin · Ying Li · Yang Sheng · Christopher R Kelsey · Yaorong Ge
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    ABSTRACT: The selection of the incident angles of the treatment beams is a critical component of intensity modulated radiation therapy (IMRT) planning for lung cancer due to significant variations in tumor location, tumor size and patient anatomy. We investigate the feasibility of establishing a small set of standardized beam bouquets for planning. The set of beam bouquets were determined by learning the beam configuration features from 60 clinical lung IMRT plans designed by experienced planners. A k-medoids cluster analysis method was used to classify the beam configurations in the dataset. The appropriate number of clusters was determined by maximizing the value of average silhouette width of the classification. Once the number of clusters had been determined, the beam arrangements in each medoid of the clusters were designated as the standardized beam bouquet for the cluster. This standardized bouquet set was used to re-plan 20 cases randomly selected from the clinical database. The dosimetric quality of the plans using the beam bouquets was evaluated against the corresponding clinical plans by a paired t-test. The classification with six clusters has the largest average silhouette width value and hence would best represent the beam bouquet patterns in the dataset. The results shows that plans generated with a small number of standardized bouquets (e.g. 6) have comparable quality to that of clinical plans. These standardized beam configuration bouquets will potentially help improve plan efficiency and facilitate automated planning.
    Physics in Medicine and Biology 02/2015; 60(5):1831-1843. DOI:10.1088/0031-9155/60/5/1831 · 2.76 Impact Factor
  • L. Yuan · Y. Ge · F. Yin · Y. Li · Y. Sheng · C.R. Kelsey · Q.J. Wu
    International journal of radiation oncology, biology, physics 09/2014; 90(1):S105-S106. DOI:10.1016/j.ijrobp.2014.05.519 · 4.26 Impact Factor
  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S629-S630. DOI:10.1016/j.ijrobp.2014.05.1871 · 4.26 Impact Factor
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    ABSTRACT: Background: The practice of treating a solitary pulmonary nodule (SPN) suspicious for stage I non-small cell lung cancer (NSCLC) with stereotactic ablative radiotherapy (SABR) in the absence of pathology is growing. In the absence of randomized evidence, the appropriate prior probability threshold of lung cancer of when such a strategy is warranted can be informed using decision analysis. Methods: A decision tree and Markov model were constructed to evaluate the relative merits of surveillance, a PET scan-directed SABR strategy (without pathology), or a PET scan-biopsy-SABR strategy, when faced with an SPN at different prior probabilities for lung cancer. Diagnostic characteristics, as well as disease, treatment, and toxicity parameters, were extracted from the literature. Deterministic analysis and probabilistic sensitivity analyses were performed to inform the appropriate lung cancer prior probability threshold between treatment strategies. Results: In the reference case analysis, the prior probability threshold between surveillance and PET scan-biopsy-SABR was 17.0%; between PET scan-directed SABR and PET scan-biopsy-SABR, the threshold was 85.0%. The latter finding was confirmed on probabilistic sensitivity analysis (85.2%; 95% CI, 80.0% to 87.2%). This predicted lung cancer prior probability threshold was most sensitive to the diagnostic sensitivity of transthoracic biopsy (range, 77.2% to 94.0%) and the detection rate of false negatives on CT scan surveillance (range, 82.4% to 92.3%). Conclusions: This model suggests that if there are concerns about morbidity related to biopsy for an SPN, a PET scan-directed SABR strategy is warranted when the prior probability of lung cancer exceeds a point estimate of 85%.
    Chest 05/2014; 146(4). DOI:10.1378/chest.13-2924 · 7.48 Impact Factor
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    ABSTRACT: Stereotactic body radiotherapy (SBRT) involves the treatment of extracranial primary tumors or metastases with a few, high doses of ionizing radiation. In SBRT, tumor kill is maximized and dose to surrounding tissue is minimized, by precise and accurate delivery of multiple radiation beams to the target. This is particularly challenging, because extracranial lesions often move with respiration and are irregular in shape, requiring careful treatment planning and continual management of this motion and patient position during irradiation. This review presents the rationale, process workflow, and technology for the safe and effective administration of SBRT, as well as the indications, outcome, and limitations for this technique in the treatment of lung cancer, liver cancer, and metastatic disease. Cancer 2013;. © 2013 American Cancer Society.
    Cancer 04/2014; 120(7). DOI:10.1002/cncr.28515 · 4.89 Impact Factor
  • Hong Ge · Jing Cai · Christopher Kelsey · Fang-Fang Yin
    International journal of radiation oncology, biology, physics 09/2013; 87(1):5-6. DOI:10.1016/j.ijrobp.2013.04.044 · 4.26 Impact Factor
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    ABSTRACT: Background: The role of surgical resection for stage IIIA non-small cell lung cancer (NSCLC) is unclear. We sought to examine outcomes after pneumonectomy for patients with stage IIIA disease. Methods: All patients with stage IIIA NSCLC who had pneumonectomy at a single institution between 1999 and 2010 were reviewed. The Kaplan-Meier method was used to estimate long-term survival and multivariable Cox proportional hazards regression was used to identify clinical characteristics associated with survival. Results: During the study period, 324 patients had surgical resection of stage IIIA NSCLC. Pneumonectomy was performed in 55 patients, 23 (42%) of whom had N2 disease. Induction treatment was used in 17 patients (31%) overall and in 11 of the patients (48%) with N2 disease. Perioperative mortality was 9% (n = 5) overall and 18% (n = 3) in patients that had received induction therapy (p = 0.17). Complications occurred in 32 patients (58%). Three-year survival was 36% and 5-year survival was 29% for all patients. Three-year survival was 40% for N0-1 patients and 29% for N2 patients (p = 0.59). In multivariable analysis, age over 60 years (hazard ratio [HR] 3.65, p = 0.001), renal insufficiency (HR 5.80, p = 0.007), and induction therapy (HR 2.17, p = 0.05) predicted worse survival, and adjuvant therapy (HR 0.35, p = 0.007) predicted improved survival. Conclusions: Long-term survival after pneumonectomy for stage IIIA NSCLC is within an acceptable range, but pneumonectomy may not be appropriate after induction therapy or in patients with renal insufficiency. Patient selection and operative technique that limit perioperative morbidity and facilitate the use of adjuvant chemotherapy are critical to optimizing outcomes.
    The Annals of thoracic surgery 03/2013; 95(5). DOI:10.1016/j.athoracsur.2013.02.044 · 3.85 Impact Factor
  • Jing Cai · Zheng Chang · Jennifer O'Daniel · Sua Yoo · Hong Ge · Christopher Kelsey · Fang-Fang Yin
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    ABSTRACT: The purpose of this study was to evaluate the sliced body volume (SBV) as a respiratory surrogate by comparing with the real-time position management (RPM) in phantom and patient cases. Using the SBV surrogate, breathing signals were extracted from unsorted 4D CT images of a motion phantom and 31 cancer patients (17 lung cancers, 14 abdominal cancers) and were compared to those clinically acquired using the RPM system. Correlation coefficient (R), phase difference (D), and absolute phase difference (DA) between the SBV-derived breathing signal and the RPM signal were calculated. 4D CT reconstructed based on the SBV surrogate (4D CTSBV) were compared to those clinically generated based on RPM (4D CTRPM). Image quality of the 4D CT were scored (SSBV and SRPM, respectively) from 1 to 5 (1 is the best) by experienced evaluators. The comparisons were performed for all patients, and for the lung cancer patients and the abdominal cancer patients separately. RPM box position (P), breathing period (T), amplitude (A), period variability (VT), amplitude variability (VA), and space-dependent phase shift (F) were determined and correlated to SSBV. The phantom study showed excellent match between the SBV-derived breathing signal and the RPM signal (R = 0.99, D= -3.0%, DA = 4.5%). In the patient study, the mean (± standard deviation (SD)) R, D, DA, T, VT, A, VA, and F were 0.92 (± 0.05), -3.3% (± 7.5%), 11.4% (± 4.6%), 3.6 (± 0.8) s, 0.19 (±0.10), 6.6 (± 2.8) mm, 0.20 (± 0.08), and 0.40 (± 0.18) s, respectively. Significant differences in R and DA (p = 0.04 and 0.001, respectively) were found between the lung cancer patients and the abdominal cancer patients. 4D CTRPM slightly outperformed 4D CTSBV: the mean (±SD) SRPM and SSBV were 2.6 (± 0.6) and 2.9 (± 0.8), respectively, for all patients, 2.5 (± 0.6) and 3.1 (± 0.8), respectively, for the lung cancer patients, and 2.6 (±0.7) and 2.8 (± 0.9), respectively, for the abdominal cancer patients. The difference between SRPM and SSBV was insignificant for the abdominal patients (p = 0.59). F correlated moderately with SSBV (r = 0.72). The correlation between SBV-derived breathing signal and RPM signal varied between patients and was significantly better in the abdomen than in the thorax. Space-dependent phase shift is a limiting factor of the accuracy of the SBV surrogate.
    Journal of Applied Clinical Medical Physics 01/2013; 14(1):3987. DOI:10.1120/jacmp.v14i1.3987 · 1.17 Impact Factor
  • Yi Hsuan Chung · Christopher Kelsey · Shiva Das
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    ABSTRACT: Purpose: To investigate the necessity for adaptive radiation therapy (RT) in lung cancer IMRT treatments by quantifying tumor changes during radiotherapy and the associated impact on target, lung and esophagus. Methods: As part of an IRB-approved lung dose escalation study, contrasted CT scans were acquired on 15 patients prior to RT and in the 2nd and 5th week of treatment (total dose=58-70 Gy, 2Gy/fraction). Target, lung and esophagus volumes were segmented in all CT datasets. The original plan was recomputed on the subsequent CT sets and doses were accumulated by deformable registration to approximate the actual delivery. Five patients with the largest tumor shrinkage were selected and re-planned on the 2nd and 5th week CT sets. The plans were summed to mimic adaptive radiation therapy. Comparisons were made between the approximated actual treatment, summation of the re-optimized plans, and the original plan. Comparison metrics included QUANTEC dose parameters, equivalent uniform dose (EUD), maximum dose and target coverage (unless otherwise stated, all percentage changes in results are with respect to the original plan, averaged over all patients). Results: The approximated actual delivery had significantly increased lung dose- volume/EUD (V5 =8.19%, V20 = 4.14%, EUD = 5.95%). Tumor shrinkage- induced esophageal volume outside the originally segmented volume (3.4%-101.8%) was significant. Elevated esophagus EUD (7.27%) and spinal cord maximum dose (6.7%) were observed in most patients. PTV/GTV volumes receiving 100% of prescription dose decreased (week 2/5 PTV = -10.0%/- 6.88%, week 2/5 GTV = -6.7%/-4.1%), along with slightly increased dose to the highest 1 % of volume. Compared to the approximated actual delivery, re-optimized plans overall showed superiority in lowered dose to the esophagus (V35=-40.32%, EUD =-13.42%), lungs (V5=-4.18%, V20=- 10.66%) and spinal cord (Dmax=-22.98%). Conclusions: RT-induced esophageal volume displacement and increased lung dose during treatment are significant, warranting re-plan in cases where large tumor changes are expected.
    Medical Physics 06/2012; 39(6):3986. DOI:10.1118/1.4736536 · 2.64 Impact Factor
  • Yuan Tian · Zhiheng Wang · Hong Ge · Tian Zhang · Jing Cai · Christopher Kelsey · David Yoo · Fang-Fang Yin
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    ABSTRACT: To determine whether there is a CT dataset may be more favorable for planning and dose calculation by comparing dosimetric characteristics between treatment plans calculated using free breathing (FB), maximum and average intensity projection (MIP and AIP, respectively) CTs for lung cancer patients receiving stereotactic body radiation therapy (SBRT). Twenty lung cancer SBRT patients, treated on a linac with 2.5 mm width multileaf-collimator (MLC), were analyzed retrospectively. Both FB helical and four-dimensional CT scans were acquired for each patient. Internal target volume (ITV) was delineated based on MIP CTs and modified based on both ten-phase datasets and FB CTs. Planning target volume (PTV) was then determined by adding additional setup margin to ITV. The PTVs and beams in the optimized treatment plan based on FB CTs were copied to MIP and AIP CTs, with the same isocenters, MLC patterns and monitor units. Mean effective depth (MED) of beams, and some dosimetric parameters for both PTVs and most important organ at risk (OAR), lung minus PTV, were compared between any two datasets using two-tail paired t test. The MEDs in FB and AIP plans were similar but significantly smaller (Ps < 0.001) than that in MIP plans. Minimum dose, mean dose, dose covering at least 90% and 95% of PTVs in MIP plans were slightly higher than two other plans (Ps < 0.008). The absolute volume of lung minus PTV receiving greater than 5, 10, and 20 Gy in MIP plans were significantly smaller than those in both FB and AIP plans (Ps < 0.008). Conformity index for FB plans showed a small but statistically significantly higher. Dosimetric characteristics of AIP plans are similar to those of FB plans. Slightly better target volume coverage and significantly lower low-dose region (≤30 Gy) in lung was observed in MIP plans. The decrease in low-dose region in lung was mainly caused by the change of lung volume contoured on two datasets rather than the differences of dose distribution between AIP and MIP plans. Compare with AIP datasets, FB datasets were more prone to significant image artifacts and MIP datasets may overestimate or underestimate the target volume when the target is closer to the denser tissue, so AIP seems favorable for planning and dose calculation for lung SBRT.
    Medical Physics 05/2012; 39(5):2754-60. DOI:10.1118/1.4705353 · 2.64 Impact Factor
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    ABSTRACT: To assess the association between radiotherapy (RT)-induced changes in computed tomography (CT)-defined lung tissue density and pulmonary function tests (PFTs). Patients undergoing incidental partial lung RT were prospectively assessed for global (PFTs) and regional (CT and single photon emission CT [SPECT]) lung function before and, serially, after RT. The percent reductions in the PFT and the average changes in lung density were compared (Pearson correlations) in the overall group and subgroups stratified according to various clinical factors. Comparisons were also made between the CT- and SPECT-based computations using the Mann-Whitney U test. Between 1991 and 2004, 343 patients were enrolled in this study. Of these, 111 patients had a total of 203 concurrent post-RT evaluations of changes in lung density and PFTs available for the analyses, and 81 patients had a total of 141 concurrent post-RT SPECT images. The average increases in lung density were related to the percent reductions in the PFTs, albeit with modest correlation coefficients (range, 0.20-0.43). The analyses also indicated that the association between lung density and PFT changes is essentially equivalent to the corresponding association with SPECT-defined lung perfusion. We found a weak quantitative association between the degree of increase in lung density as defined by CT and the percent reduction in the PFTs.
    International journal of radiation oncology, biology, physics 07/2009; 74(3):781-9. DOI:10.1016/j.ijrobp.2008.08.053 · 4.26 Impact Factor
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    ABSTRACT: To study the temporal nature of regional lung density changes and to assess whether the dose-dependent nature of these changes is associated with patient- and treatment-associated factors. Between 1991 and 2004, 118 patients with interpretable pre- and post-radiation therapy (RT) chest computed tomography (CT) scans were evaluated. Changes in regional lung density were related to regional dose to define a dose-response curve (DRC) for RT-induced lung injury using three-dimensional planning tools and image fusion. Multiple post-RT follow-up CT scans were evaluated by fitting linear-quadratic models of density changes on dose with time as the covariate. Various patient- and treatment-related factors were examined as well. There was a dose-dependent increase in regional lung density at nearly all post-RT follow-up intervals. The population volume-weighted changes evolved over the initial 6-month period after RT and reached a plateau thereafter (p < 0.001). On univariate analysis, patient age greater than 65 years (p = 0.003) and/or the use of pre-RT surgery (p < 0.001) were associated with significantly greater changes in CT density at both 6 and 12 months after RT, but the magnitude of this effect was modest. There appears to be a temporal nature for the dose-dependent increases in lung density. Nondosimetric clinical factors tend to have no, or a modest, impact on these changes.
    International journal of radiation oncology, biology, physics 04/2009; 76(1):116-22. DOI:10.1016/j.ijrobp.2009.01.025 · 4.26 Impact Factor
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    ABSTRACT: To assess the safety and efficacy of intensity-modulated radiotherapy (IMRT) after extrapleural pneumonectomy for malignant pleural mesothelioma. Thirteen patients underwent IMRT after extrapleural pneumonectomy between July 2005 and February 2007 at Duke University Medical Center. The clinical target volume was defined as the entire ipsilateral hemithorax, chest wall incisions, including drain sites, and involved nodal stations. The dose prescribed to the planning target volume was 40-55 Gy (median, 45). Toxicity was graded using the modified Common Toxicity Criteria, and the lung dosimetric parameters from the subgroups with and without pneumonitis were compared. Local control and survival were assessed. The median follow-up after IMRT was 9.5 months. Of the 13 patients, 3 (23%) developed Grade 2 or greater acute pulmonary toxicity (during or within 30 days of IMRT). The median dosimetric parameters for those with and without symptomatic pneumonitis were a mean lung dose (MLD) of 7.9 vs. 7.5 Gy (p = 0.40), percentage of lung volume receiving 20 Gy (V(20)) of 0.2% vs. 2.3% (p = 0.51), and percentage of lung volume receiving 5 Gy (V(20)) of 92% vs. 66% (p = 0.36). One patient died of fatal pulmonary toxicity. This patient received a greater MLD (11.4 vs. 7.6 Gy) and had a greater V(20) (6.9% vs. 1.9%), and V(5) (92% vs. 66%) compared with the median of those without fatal pulmonary toxicity. Local and/or distant failure occurred in 6 patients (46%), and 6 patients (46%) were alive without evidence of recurrence at last follow-up. With limited follow-up, 45-Gy IMRT provides reasonable local control for mesothelioma after extrapleural pneumonectomy. However, treatment-related pulmonary toxicity remains a significant concern. Care should be taken to minimize the dose to the remaining lung to achieve an acceptable therapeutic ratio.
    International Journal of Radiation OncologyBiologyPhysics 08/2008; 71(4):1143-50. DOI:10.1016/j.ijrobp.2007.11.011 · 4.26 Impact Factor
  • Paiman Ghafoori · Lawrence B Marks · Zeljko Vujaskovic · Christopher R Kelsey
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    ABSTRACT: Radiation therapy (RT) is an important treatment modality for multiple thoracic malignancies. Incidental irradiation of the lungs, which are particularly susceptible to injury, is unavoidable and often dose-limiting. The most radiosensitive subunit of the lung is the alveolar/capillary complex, and RT-induced lung injury is often described as diffuse alveolar damage. Reactive oxygen species generated by RT are directly toxic to parenchymal cells and initiate a cascade of molecular events that alter the cytokine milieu of the microenvironment, creating a self-sustaining cycle of inflammation and chronic oxidative stress. Replacement of normal lung parenchyma by fibrosis is the culminating event. Depending on the dose and volume of lung irradiated, acute radiation pneumonitis may develop, characterized by dry cough and dyspnea. Fibrosis of the lung, which can also cause dyspnea, is the late complication. Imaging studies and pulmonary function tests can be used to quantify the extent of lung injury. While strict dose-volume constraints to minimize the risk of injury are difficult to impose, substantial data support some general guidelines. New modalities such as intensity-modulated radiation therapy and stereotactic body radiation therapy provide new treatment options but also pose new challenges in safely delivering thoracic RT.
    Oncology (Williston Park, N.Y.) 02/2008; 22(1):37-47; discussion 52-3. · 2.32 Impact Factor