skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Serial megavoltage CT imaging during external beam radiotherapy for non-small-cell lung cancer: Observations on tumor regression during treatment

Abstract

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 sets 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 overmore » 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

Authors:
 [1];  [2];  [3];  [3];  [3];  [3];  [3]
  1. Department of Radiation Oncology, M.D. Anderson Cancer Center Orlando, Orlando, FL (United States). E-mail: kupelian@orhs.org
  2. Department of Radiation Oncology, Thompson Cancer Survival Center, Knoxville, TN (United States)
  3. Department of Radiation Oncology, M.D. Anderson Cancer Center Orlando, Orlando, FL (United States)
Publication Date:
OSTI Identifier:
20706244
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 63; Journal Issue: 4; Other Information: DOI: 10.1016/j.ijrobp.2005.04.046; PII: S0360-3016(05)00818-7; Copyright (c) 2005 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; ATTENUATION; CARCINOMAS; COMPUTERIZED TOMOGRAPHY; DOCUMENTATION; IMAGES; LUNGS; PATIENTS; RADIATION DOSES; RADIOTHERAPY

Citation Formats

Kupelian, Patrick A., Ramsey, Chester, Meeks, Sanford L., Willoughby, Twyla R., Forbes, Alan, Wagner, Thomas H., and Langen, Katja M. Serial megavoltage CT imaging during external beam radiotherapy for non-small-cell lung cancer: Observations on tumor regression during treatment. United States: N. p., 2005. Web. doi:10.1016/j.ijrobp.2005.04.046.
Kupelian, Patrick A., Ramsey, Chester, Meeks, Sanford L., Willoughby, Twyla R., Forbes, Alan, Wagner, Thomas H., & Langen, Katja M. Serial megavoltage CT imaging during external beam radiotherapy for non-small-cell lung cancer: Observations on tumor regression during treatment. United States. doi:10.1016/j.ijrobp.2005.04.046.
Kupelian, Patrick A., Ramsey, Chester, Meeks, Sanford L., Willoughby, Twyla R., Forbes, Alan, Wagner, Thomas H., and Langen, Katja M. Tue . "Serial megavoltage CT imaging during external beam radiotherapy for non-small-cell lung cancer: Observations on tumor regression during treatment". United States. doi:10.1016/j.ijrobp.2005.04.046.
@article{osti_20706244,
title = {Serial megavoltage CT imaging during external beam radiotherapy for non-small-cell lung cancer: Observations on tumor regression during treatment},
author = {Kupelian, Patrick A. and Ramsey, Chester and Meeks, Sanford L. and Willoughby, Twyla R. and Forbes, Alan and Wagner, Thomas H. and Langen, Katja M.},
abstractNote = {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 sets 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.},
doi = {10.1016/j.ijrobp.2005.04.046},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 63,
place = {United States},
year = {Tue Nov 15 00:00:00 EST 2005},
month = {Tue Nov 15 00:00:00 EST 2005}
}
  • Purpose: Adaptive radiotherapy allows treatment plan modification based on data obtained during treatment. Assessing volume changes during treatment is now possible with intratreatment imaging capabilities on radiotherapy devices. This study assesses non-small-cell lung cancer (NSCLC) volume changes during treatment with conformal intensity-modulated radiotherapy by evaluating serial megavoltage computed tomography (MVCT) scans, with a specific emphasis on the frequency, reliability, and meaningfulness of these changes. Methods and Materials: Megavoltage CTs were retrospectively reviewed for 25 patients treated with the TomoTherapy Hi-Art system at University of Wisconsin. Twenty-one patients received definitive radiotherapy, 4 with extracranial stereotactic radioablation (60 Gy in five fractions)more » and 17 on a dose-per-fraction escalation protocol (57-80.5 Gy in 25 fractions). Four patients were treated palliatively (22-30 Gy in 8 to 10 fractions). Gross tumor volumes were contoured on serial MVCTs at weekly intervals. Each patient had 4 to 25 scans, including at least one at the beginning, midway, and one at the end of treatment. Results: At completion of treatment, no patient demonstrated a complete response. Partial response occurred in 3 (12%) and marginal response was noted in 5 (20%). The remaining 17 patients (68%) showed stable disease. The minimum 'scorable threshold' for volume discrepancy between scans to account for interscan assessment variability was set at >25% volume change; 10 patients (40%) had >25% tumor regression. None of the patients treated ablatively or palliatively showed tumor regression during treatment. Conclusions: Although gross tumor regression during treatment may be objectively measured using MVCTs, substantial volumetric decrease occurs only in a minority. The clinical significance of this regression is questionable, because there is no way to document histologic tumor clearance, and therefore field reductions during radiotherapy cannot be recommended.« 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: To establish whether {sup 18}F-3'-deoxy-3'-fluoro-L-thymidine ({sup 18}F-FLT) can monitor changes in cellular proliferation of non-small-cell lung cancer (NSCLC) during radical chemo-radiotherapy (chemo-RT). Methods and Materials: As part of a prospective pilot study, 5 patients with locally advanced NSCLC underwent serial {sup 18}F-FLT positron emission tomography (PET)/computed tomography (CT) scans during treatment. Baseline {sup 18}F-FLT PET/CT scans were compared with routine staging {sup 18}F-FDG PET/CT scans. Two on-treatment {sup 18}F-FLT scans were performed for each patient on Days 2, 8, 15 or 29, providing a range of time points for response assessment. Results: In all 5 patients, baseline lesional uptakemore » of {sup 18}F-FLT on PET/CT corresponded to staging {sup 18}F-FDG PET/CT abnormalities. {sup 18}F-FLT uptake in tumor was observed on five of nine (55%) on-treatment scans, on Days 2, 8 and 29, but not Day 15. A 'flare' of {sup 18}F-FLT uptake in the primary tumor of one case was observed after 2 Gy of radiation (1.22 x baseline). The remaining eight on-treatment scans demonstrated a mean reduction in {sup 18}F-FLT tumor uptake of 0.58 x baseline. A marked reduction of {sup 18}F-FLT uptake in irradiated bone marrow was observed for all cases. This reduction was observed even after only 2 Gy, and all patients demonstrated a complete absence of proliferating marrow after 10 Gy. Conclusions: This proof of concept study indicates that {sup 18}F-FLT uptake can monitor the distinctive biologic responses of epithelial cancers and highly radiosensitive normal tissue changes during radical chemo-RT. Further studies of {sup 18}F-FLT PET/CT imaging during therapy may suggest that this tracer is useful in developing response-adapted RT for NSCLC.« less
  • Purpose: To evaluate prospectively how positron emission tomography (PET) information changes treatment plans for non-small-cell lung cancer (NSCLC) patients receiving or not receiving elective nodal irradiation (ENI). Methods and Materials: One hundred consecutive patients referred for curative radiotherapy were included in the study. Treatment plans were carried out with CT data sets only. For stage III patients, mediastinal ENI was planned. Then, patients underwent PET-CT for diagnostic/planning purposes. PET/CT was fused with the CT data for final planning. New targets were delineated. For stage III patients with minimal N disease (N0-N1, single N2), the ENI was omitted in the newmore » plans. Patients were treated according to the PET-based volumes and plans. The gross tumor volume (GTV)/planning tumor volume (PTV) and doses for critical structures were compared for both data sets. The doses for areas of potential geographical misses derived with the CT data set alone were compared in patients with and without initially planned ENI. Results: In the 75 patients for whom the decision about curative radiotherapy was maintained after PET/CT, there would have been 20 cases (27%) with potential geographical misses by using the CT data set alone. Among them, 13 patients would receive ENI; of those patients, only 2 patients had the PET-based PTV covered by 90% isodose by using the plans based on CT alone, and the mean of the minimum dose within the missed GTV was 55% of the prescribed dose, while for 7 patients without ENI, it was 10% (p = 0.006). The lung, heart, and esophageal doses were significantly lower for plans with ENI omission than for plans with ENI use based on CT alone. Conclusions: PET/CT should be incorporated in the planning of radiotherapy for NSCLC, even in the setting of ENI. However, if PET/CT is unavailable, ENI may to some extent compensate for an inadequate dose coverage resulting from diagnostic uncertainties.« less
  • 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.more » 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.« less