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Title: Locoregional Control of Non-Small Cell Lung Cancer in Relation to Automated Early Assessment of Tumor Regression on Cone Beam Computed Tomography

Abstract

Purpose: Large interindividual variations in volume regression of non-small cell lung cancer (NSCLC) are observable on standard cone beam computed tomography (CBCT) during fractionated radiation therapy. Here, a method for automated assessment of tumor volume regression is presented and its potential use in response adapted personalized radiation therapy is evaluated empirically. Methods and Materials: Automated deformable registration with calculation of the Jacobian determinant was applied to serial CBCT scans in a series of 99 patients with NSCLC. Tumor volume at the end of treatment was estimated on the basis of the first one third and two thirds of the scans. The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearson's correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2 groups having volume regressions below or above the population median value. Kaplan-Meier plots of locoregional disease-free rate and overall survival in the 2 groups were used to evaluate the predictive value of tumor regression during treatment. Cox proportional hazards model was used to adjust for other clinical characteristics. Results: Automatic measurement of the tumor regression from standard CBCT images was feasible. Pearson's correlation coefficient between manualmore » and automatic measurement was 0.86 in a sample of 9 patients. Most patients experienced tumor volume regression, and this could be quantified early into the treatment course. Interestingly, patients with pronounced volume regression had worse locoregional tumor control and overall survival. This was significant on patient with non-adenocarcinoma histology. Conclusions: Evaluation of routinely acquired CBCT images during radiation therapy provides biological information on the specific tumor. This could potentially form the basis for personalized response adaptive therapy.« less

Authors:
 [1];  [2];  [1];  [2];  [3];  [1];  [2];  [4];  [5]
  1. Institute of Clinical Research, University of Southern Denmark (Denmark)
  2. (Denmark)
  3. Laboratory of Radiation Physics, Odense University Hospital (Denmark)
  4. Department of Oncology, Odense University Hospital (Denmark)
  5. Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD (United States)
Publication Date:
OSTI Identifier:
22420379
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 89; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; COMPUTERIZED TOMOGRAPHY; HAZARDS; HISTOLOGY; LUNGS; PATIENTS; RADIOTHERAPY

Citation Formats

Brink, Carsten, E-mail: carsten.brink@rsyd.dk, Laboratory of Radiation Physics, Odense University Hospital, Bernchou, Uffe, Laboratory of Radiation Physics, Odense University Hospital, Bertelsen, Anders, Hansen, Olfred, Department of Oncology, Odense University Hospital, Schytte, Tine, and Bentzen, Soren M.. Locoregional Control of Non-Small Cell Lung Cancer in Relation to Automated Early Assessment of Tumor Regression on Cone Beam Computed Tomography. United States: N. p., 2014. Web. doi:10.1016/J.IJROBP.2014.03.038.
Brink, Carsten, E-mail: carsten.brink@rsyd.dk, Laboratory of Radiation Physics, Odense University Hospital, Bernchou, Uffe, Laboratory of Radiation Physics, Odense University Hospital, Bertelsen, Anders, Hansen, Olfred, Department of Oncology, Odense University Hospital, Schytte, Tine, & Bentzen, Soren M.. Locoregional Control of Non-Small Cell Lung Cancer in Relation to Automated Early Assessment of Tumor Regression on Cone Beam Computed Tomography. United States. doi:10.1016/J.IJROBP.2014.03.038.
Brink, Carsten, E-mail: carsten.brink@rsyd.dk, Laboratory of Radiation Physics, Odense University Hospital, Bernchou, Uffe, Laboratory of Radiation Physics, Odense University Hospital, Bertelsen, Anders, Hansen, Olfred, Department of Oncology, Odense University Hospital, Schytte, Tine, and Bentzen, Soren M.. Tue . "Locoregional Control of Non-Small Cell Lung Cancer in Relation to Automated Early Assessment of Tumor Regression on Cone Beam Computed Tomography". United States. doi:10.1016/J.IJROBP.2014.03.038.
@article{osti_22420379,
title = {Locoregional Control of Non-Small Cell Lung Cancer in Relation to Automated Early Assessment of Tumor Regression on Cone Beam Computed Tomography},
author = {Brink, Carsten, E-mail: carsten.brink@rsyd.dk and Laboratory of Radiation Physics, Odense University Hospital and Bernchou, Uffe and Laboratory of Radiation Physics, Odense University Hospital and Bertelsen, Anders and Hansen, Olfred and Department of Oncology, Odense University Hospital and Schytte, Tine and Bentzen, Soren M.},
abstractNote = {Purpose: Large interindividual variations in volume regression of non-small cell lung cancer (NSCLC) are observable on standard cone beam computed tomography (CBCT) during fractionated radiation therapy. Here, a method for automated assessment of tumor volume regression is presented and its potential use in response adapted personalized radiation therapy is evaluated empirically. Methods and Materials: Automated deformable registration with calculation of the Jacobian determinant was applied to serial CBCT scans in a series of 99 patients with NSCLC. Tumor volume at the end of treatment was estimated on the basis of the first one third and two thirds of the scans. The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearson's correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2 groups having volume regressions below or above the population median value. Kaplan-Meier plots of locoregional disease-free rate and overall survival in the 2 groups were used to evaluate the predictive value of tumor regression during treatment. Cox proportional hazards model was used to adjust for other clinical characteristics. Results: Automatic measurement of the tumor regression from standard CBCT images was feasible. Pearson's correlation coefficient between manual and automatic measurement was 0.86 in a sample of 9 patients. Most patients experienced tumor volume regression, and this could be quantified early into the treatment course. Interestingly, patients with pronounced volume regression had worse locoregional tumor control and overall survival. This was significant on patient with non-adenocarcinoma histology. Conclusions: Evaluation of routinely acquired CBCT images during radiation therapy provides biological information on the specific tumor. This could potentially form the basis for personalized response adaptive therapy.},
doi = {10.1016/J.IJROBP.2014.03.038},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 89,
place = {United States},
year = {Tue Jul 15 00:00:00 EDT 2014},
month = {Tue Jul 15 00:00:00 EDT 2014}
}
  • Purpose: Quantification of volume changes on CBCT during SBRT for NSCLC may provide a useful radiological marker for radiation response and adaptive treatment planning, but the reproducibility of CBCT volume delineation is a concern. This study is to quantify inter-scan/inter-observer variability in tumor volume delineation on CBCT. Methods: Twenty earlystage (stage I and II) NSCLC patients were included in this analysis. All patients were treated with SBRT with a median dose of 54 Gy in 3 to 5 fractions. Two physicians independently manually contoured the primary gross tumor volume on CBCTs taken immediately before SBRT treatment (Pre) and after themore » same SBRT treatment (Post). Absolute volume differences (AVD) were calculated between the Pre and Post CBCTs for a given treatment to quantify inter-scan variability, and then between the two observers for a given CBCT to quantify inter-observer variability. AVD was also normalized with respect to average volume to obtain relative volume differences (RVD). Bland-Altman approach was used to evaluate variability. All statistics were calculated with SAS version 9.4. Results: The 95% limit of agreement (mean ± 2SD) on AVD and RVD measurements between Pre and Post scans were −0.32cc to 0.32cc and −0.5% to 0.5% versus −1.9 cc to 1.8 cc and −15.9% to 15.3% for the two observers respectively. The 95% limit of agreement of AVD and RVD between the two observers were −3.3 cc to 2.3 cc and −42.4% to 28.2% respectively. The greatest variability in inter-scan RVD was observed with very small tumors (< 5 cc). Conclusion: Inter-scan variability in RVD is greatest with small tumors. Inter-observer variability was larger than inter-scan variability. The 95% limit of agreement for inter-observer and inter-scan variability (∼15–30%) helps define a threshold for clinically meaningful change in tumor volume to assess SBRT response, with larger thresholds needed for very small tumors. Part of the work was funded by a Kaye award; Disclosure/Conflict of interest: Raymond H. Mak: Stock ownership: Celgene, Inc. Consulting: Boehringer-Ingelheim, Inc.« less
  • Purpose: To investigate the magnitudes of the changes in mobility and volume of locally advanced non-small-cell lung cancer (NSCLC) tumors during radiotherapy, using four-dimensional computed tomography (4DCT). Methods and Materials: Five to ten 4DCT data sets were acquired weekly for each of 8 patients throughout treatment. Gross tumor volumes (GTVs) were outlined on each data set. Volumes and coordinates of the GTV centroids were calculated at the 0 (end-inspiration) and 50% (end-expiration) respiration phases. Trends in magnitudes of intrafraction and interfraction positional variations were assessed for the GTV and internal target volume (ITV) during treatment. Results: Tumor volume reduction rangedmore » from 20% to 71% (end-inspiration) and from 15% to 70% (end-expiration). Increased tumor mobility was observed in the superior-inferior and anterior-posterior directions. However, no trends in tumor motion were observed. Motion along the superior-inferior direction was significantly greater (p < 0.001), with mean {+-} SD values of 0.86 {+-} 0.19 cm, as compared with 0.39 {+-} 0.08 cm and 0.19 {+-} 0.05 cm in the anterior-posterior and right-left directions, respectively. A marginally significant (p = 0.049) increase in total GTV positional variation was observed with increasing treatment weeks, and similar results were seen for the interfractional ITV mobility. Conclusions: Because of changes in tumor size and mobility, an explicit initial determination of the ITV may not be sufficient, especially where small setup margins are used. Repeat 4DCT scans might be warranted for highly mobile tumors to reduce the potential for missing the tumor.« less
  • Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinicalmore » information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes.« less
  • Purpose: To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. Methods and Materials: Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET)more » CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. Results: Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade {>=}2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). Conclusion: Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will increase the likelihood of correctly identifying patients with progressive disease after lung SBRT.« less
  • Purpose: The ability to obtain soft-tissue imaging in the treatment room, such as with megavoltage CT imaging, enables the observation of tumor regression during a course of external beam radiation therapy. In this current study, we report on the most extensive study looking at the rate of regression of non-small-cell lung cancers during a course of external beam radiotherapy by analyzing serial megavoltage CT images obtained on 10 patients. Methods and Materials: The analysis is performed on 10 patients treated with the Helical Tomotherapy Hi*Art device. All 10 patients had non-small-cell lung cancer. A total of 274 megavoltage CT setsmore » were obtained on the 10 patients (average, 27 scans per patient; range, 9-35). All patients had at least a scan at beginning and at the end of treatment. The frequency of scanning was determined by the treating physician. The treatment was subsequently delivered with the Tomotherapy Hi*Art system. The gross tumor volumes (GTVs) were later contoured on each megavoltage CT scan, and tumor volumes were calculated. Although some patients were treated to draining nodal areas in addition to the primary tumor, only the primary GTVs were tracked. Response to treatment was quantified by the relative decrease in tumor volume over time, i.e., elapsed days from the first day of therapy. The individual GTVs ranged from 5.9 to 737.2 cc in volume at the start of treatment. In 6 of the 10 patients, dose recalculations were also performed to document potential variations in delivered doses within the tumors. The megavoltage CT scans were used, and the planned treatment was recalculated on the daily images. The hypothesis was that dose deposited in the target would increase throughout the course of radiotherapy because of tumor shrinkage and subsequent decreasing attenuation. Specifically, the dose received by 95% of the GTV (D{sub 95}) was monitored over time for each of the 6 patients treated at M.D. Anderson Cancer Center Orlando. Results: Regression of all 10 lung tumors could be observed on the serial megavoltage CT scans. The decrease in volume was observed at a relatively constant rate throughout the treatments, with no obvious initial or final plateaus. For all 10 tumors, the average decrease in volume was 1.2% per day. However, individual tumor regression rates were observed with a range of 0.6% to 2.3% per day. The lowest rate of shrinkage was observed for the smallest lesion, and the highest rate was observed in the largest lesion. Of the 6 cases in which dose recalculations were performed, 5 demonstrated a small but noticeable gradual increase in deposited doses within the tumor, with the D{sub 95} increases ranging from 0.02% to 0.1% per day. Conclusion: With the advent of in-room soft-tissue imaging techniques such as megavoltage CT imaging with a helical tomotherapy unit, daily documentation of the status of a grossly visible targeted tumor becomes possible. The current study demonstrated that tumor regression can be documented for patients with non-small-cell lung cancer treated with helical tomotherapy. Clinical correlations between the observations made during the course of treatment and ultimate outcomes, e.g. local control, should be investigated.« less