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Title: Hypoxia Dose Painting by Numbers: A Planning Study

Abstract

Purpose: To investigate the feasibility of different hypoxia dose painting strategies in head-and-neck radiotherapy; the potential benefit was limited by the stipulation of isotoxicity with respect to the conventional intensity-modulated radiotherapy (IMRT) treatment. Methods and Materials: Thirteen head-and-neck cancer patients were included into the planning study. For each patient, three different treatment plans were created: a conventional IMRT plan, an additional uniform dose escalation (uniDE) of 10% to the fluorodeoxyglucose (FDG)-positive volume, and a plan in which dose painting by numbers (DPBN) was implemented. Dose painting by numbers was realized according to a map of dose-escalation factors calculated from dynamic [{sup 18}F]-fluoromisonidazole (FMISO) positron emission tomography data. Results: Both dose-escalation approaches were shown to be feasible under the constraint of limiting normal tissue doses to the level of conventional IMRT. For DPBN, the prescriptions could be fulfilled in larger regions of the target than for uniDE. Fluorodeoxyglucose-positive volumes had sizes up to 94 cm{sup 3}. In contrast, regions receiving comparable dose levels with DPBN presented volumes in the range of 0-2.7 cm{sup 3}. Overtreatment of the target was observed with uniDE in most of the cases, whereas some regions did not receive the required dose to overcome hypoxia-induced radiation insensitivity.more » Tumor control probability increased from 55.9% with conventional IMRT to 57.7% for the uniDE method in the patient group. For DPBN, a potential increase in tumor control probability from 55.9% to 70.2% was determined. Therefore, DPBN seems to result in higher benefits for the patients. Conclusion: Dose painting by numbers delivers the dose more effectively than an additional uniform boost to the FDG-positive area. If hypoxia could be adequately quantified with a simple imaging technique like FMISO positron emission tomography, DPBN in head-and-neck cancer could substantially increase tumor control.« less

Authors:
 [1];  [2];  [3];  [4]
  1. Section for Biomedical Physics, Clinic for Radiation Oncology, University Hospital Tuebingen, Tuebingen (Germany). E-mail: daniela.thorwarth@med.uni-tuebingen.de
  2. Department of Nuclear Medicine, Radiological Clinic, University Hospital Tuebingen, Tuebingen (Germany)
  3. Department of Radiation Therapy, Clinic for Radiation Oncology, University Hospital Tuebingen, Tuebingen (Germany)
  4. Section for Biomedical Physics, Clinic for Radiation Oncology, University Hospital Tuebingen, Tuebingen (Germany)
Publication Date:
OSTI Identifier:
20951645
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 68; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2006.11.061; PII: S0360-3016(07)00127-7; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, 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; ANOXIA; FLUORINE 18; FLUORODEOXYGLUCOSE; HEAD; NECK; NEOPLASMS; PATIENTS; PLANNING; POSITRON COMPUTED TOMOGRAPHY; RADIATION DOSES; RADIOTHERAPY

Citation Formats

Thorwarth, Daniela, Eschmann, Susanne-Martina, Paulsen, Frank, and Alber, Markus. Hypoxia Dose Painting by Numbers: A Planning Study. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.11.061.
Thorwarth, Daniela, Eschmann, Susanne-Martina, Paulsen, Frank, & Alber, Markus. Hypoxia Dose Painting by Numbers: A Planning Study. United States. doi:10.1016/j.ijrobp.2006.11.061.
Thorwarth, Daniela, Eschmann, Susanne-Martina, Paulsen, Frank, and Alber, Markus. Tue . "Hypoxia Dose Painting by Numbers: A Planning Study". United States. doi:10.1016/j.ijrobp.2006.11.061.
@article{osti_20951645,
title = {Hypoxia Dose Painting by Numbers: A Planning Study},
author = {Thorwarth, Daniela and Eschmann, Susanne-Martina and Paulsen, Frank and Alber, Markus},
abstractNote = {Purpose: To investigate the feasibility of different hypoxia dose painting strategies in head-and-neck radiotherapy; the potential benefit was limited by the stipulation of isotoxicity with respect to the conventional intensity-modulated radiotherapy (IMRT) treatment. Methods and Materials: Thirteen head-and-neck cancer patients were included into the planning study. For each patient, three different treatment plans were created: a conventional IMRT plan, an additional uniform dose escalation (uniDE) of 10% to the fluorodeoxyglucose (FDG)-positive volume, and a plan in which dose painting by numbers (DPBN) was implemented. Dose painting by numbers was realized according to a map of dose-escalation factors calculated from dynamic [{sup 18}F]-fluoromisonidazole (FMISO) positron emission tomography data. Results: Both dose-escalation approaches were shown to be feasible under the constraint of limiting normal tissue doses to the level of conventional IMRT. For DPBN, the prescriptions could be fulfilled in larger regions of the target than for uniDE. Fluorodeoxyglucose-positive volumes had sizes up to 94 cm{sup 3}. In contrast, regions receiving comparable dose levels with DPBN presented volumes in the range of 0-2.7 cm{sup 3}. Overtreatment of the target was observed with uniDE in most of the cases, whereas some regions did not receive the required dose to overcome hypoxia-induced radiation insensitivity. Tumor control probability increased from 55.9% with conventional IMRT to 57.7% for the uniDE method in the patient group. For DPBN, a potential increase in tumor control probability from 55.9% to 70.2% was determined. Therefore, DPBN seems to result in higher benefits for the patients. Conclusion: Dose painting by numbers delivers the dose more effectively than an additional uniform boost to the FDG-positive area. If hypoxia could be adequately quantified with a simple imaging technique like FMISO positron emission tomography, DPBN in head-and-neck cancer could substantially increase tumor control.},
doi = {10.1016/j.ijrobp.2006.11.061},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 68,
place = {United States},
year = {Tue May 01 00:00:00 EDT 2007},
month = {Tue May 01 00:00:00 EDT 2007}
}
  • Purpose: To evaluate the role of hypoxia positron emission tomography (PET) using [{sup 18}F]fluoroazomycin-arabinoside (FAZA) in head and neck cancer for radiation treatment planning using intensity-modulated radiotherapy and dose painting. Methods and Materials: Eighteen patients with advanced squamous cell head and neck cancer were included. Both FAZA-PET and axial CT were performed using mask fixation. The data were coregistered using software based on mutual information. Contours of tumor (primary gross tumor volume, GTV/CT-P) and lymph node metastases (GTV/CT-N) were outlined manually, and FAZA standardized uptake values (SUVs) were calculated automatically. The hypoxic subvolume (GTV/PET-FAZA) having at least 50% more FAZAmore » uptake than background (mean SUV) neck muscle tissue was contoured automatically within GTV/CT-P (GTV/PET-FAZA-P) and GTV/CT-N (GTV/PET-FAZA-N). Results: The median GTV/PET-FAZA-P was 4.6 mL, representing 10.8% (range, 0.7-52%) of the GTV/CT-P. The GTV/PET-FAZA-P failed to correlate significantly with the GTV/CT-P (p = 0.06). The median GTV/PET-FAZA-N was 4.1 mL, representing 8.3% (range, 2.2-51.3%) of the GTV/CT-N. It was significantly correlated with the GTV/PET-N (p = 0.006). The GTV/PET-FAZA-P was located in a single confluent area in 11 of 18 patients (61%) and was diffusely dispersed in the whole GTV/CT-P in 4 of 18 patients (22%), whereas no hypoxic areas were identified in 3 of 18 patients (17%). The GTV/PET-FAZA-N was outlined as a single confluent region in 7 of 18 patients (39%), in multiple diffuse hypoxic regions in 4 of 18 patients (22%), and was not delineated in 7 of 18 patients (39%). Conclusion: This study demonstrates that FAZA-PET imaging could be used for a hypoxia-directed intensity-modulated radiotherapy approach in head and neck cancer.« less
  • Purpose: To evaluate how changes in tumor hypoxia, according to serial fluorine-18-labeled fluoro-misonidazole ({sup 18}F-FMISO) positron emission tomography (PET) imaging, affect the efficacy of intensity-modulated radiotherapy (IMRT) dose painting. Methods and Materials: Seven patients with head and neck cancers were imaged twice with FMISO PET, separated by 3 days, before radiotherapy. Intensity-modulated radiotherapy plans were designed, on the basis of the first FMISO scan, to deliver a boost dose of 14 Gy to the hypoxic volume, in addition to the 70-Gy prescription dose. The same plans were then applied to hypoxic volumes from the second FMISO scan, and the efficacymore » of dose painting evaluated by assessing coverage of the hypoxic volumes using D{sub max}, D{sub min}, D{sub mean}, D{sub 95}, and equivalent uniform dose (EUD). Results: Similar hypoxic volumes were observed in the serial scans for 3 patients but dissimilar ones for the other 4. There was reduced coverage of hypoxic volumes of the second FMISO scan relative to that of the first scan (e.g., the average EUD decreased from 87 Gy to 80 Gy). The decrease was dependent on the similarity of the hypoxic volumes of the two scans (e.g., the average EUD decrease was approximately 4 Gy for patients with similar hypoxic volumes and approximately 12 Gy for patients with dissimilar ones). Conclusions: The changes in spatial distribution of tumor hypoxia, as detected in serial FMISO PET imaging, compromised the coverage of hypoxic tumor volumes achievable by dose-painting IMRT. However, dose painting always increased the EUD of the hypoxic volumes.« less
  • Purpose: To investigate the feasibility of adaptive intensity-modulated radiation therapy (IMRT) using dose painting by numbers (DPBN) for head-and-neck cancer. Methods and Materials: Each patient's treatment used three separate treatment plans: fractions 1-10 used a DPBN ([{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography [{sup 18}F-FDG-PET]) voxel intensity-based IMRT plan based on a pretreatment {sup 18}F-FDG-PET/computed tomography (CT) scan; fractions 11-20 used a DPBN plan based on a {sup 18}F-FDG-PET/CT scan acquired after the eighth fraction; and fractions 21-32 used a conventional (uniform dose) IMRT plan. In a Phase I trial, two dose prescription levels were tested: a median dose of 80.9 Gymore » to the high-dose clinical target volume (CTV{sub highdose}) (dose level I) and a median dose of 85.9 Gy to the gross tumor volume (GTV) (dose level II). Between February 2007 and August 2009, 7 patients at dose level I and 14 patients at dose level II were enrolled. Results: All patients finished treatment without a break, and no Grade 4 acute toxicity was observed. Treatment adaptation (i.e., plans based on the second {sup 18}F-FDG-PET/CT scan) reduced the volumes for the GTV (41%, p = 0.01), CTV{sub highdose} (18%, p = 0.01), high-dose planning target volume (14%, p = 0.02), and parotids (9-12%, p < 0.05). Because the GTV was much smaller than the CTV{sub highdose} and target adaptation, further dose escalation at dose level II resulted in less severe toxicity than that observed at dose level I. Conclusion: To our knowledge, this represents the first clinical study that combines adaptive treatments with dose painting by numbers. Treatment as described above is feasible.« less
  • Purpose: To assess the accuracy of contour deformation and feasibility of dose summation applying deformable image coregistration in adaptive dose painting by numbers (DPBN) for head and neck cancer. Methods and Materials: Data of 12 head-and-neck-cancer patients treated within a Phase I trial on adaptive {sup 18}F-FDG positron emission tomography (PET)-guided DPBN were used. Each patient had two DPBN treatment plans: the initial plan was based on a pretreatment PET/CT scan; the second adapted plan was based on a PET/CT scan acquired after 8 fractions. The median prescription dose to the dose-painted volume was 30 Gy for both DPBN plans.more » To obtain deformed contours and dose distributions, pretreatment CT was deformed to per-treatment CT using deformable image coregistration. Deformed contours of regions of interest (ROI{sub def}) were visually inspected and, if necessary, adjusted (ROI{sub def{sub ad}}) and both compared with manually redrawn ROIs (ROI{sub m}) using Jaccard (JI) and overlap indices (OI). Dose summation was done on the ROI{sub m}, ROI{sub def{sub ad}}, or their unions with the ROI{sub def}. Results: Almost all deformed ROIs were adjusted. The largest adjustment was made in patients with substantially regressing tumors: ROI{sub def} = 11.8 {+-} 10.9 cm{sup 3} vs. ROI{sub def{sub ad}} = 5.9 {+-} 7.8 cm{sup 3} vs. ROI{sub m} = 7.7 {+-} 7.2 cm{sup 3} (p = 0.57). The swallowing structures were the most frequently adjusted ROIs with the lowest indices for the upper esophageal sphincter: JI = 0.3 (ROI{sub def}) and 0.4 (ROI{sub def{sub ad}}); OI = 0.5 (both ROIs). The mandible needed the least adjustment with the highest indices: JI = 0.8 (both ROIs), OI = 0.9 (ROI{sub def}), and 1.0 (ROI{sub def{sub ad}}). Summed doses differed non-significantly. There was a trend of higher doses in the targets and lower doses in the spinal cord when doses were summed on unions. Conclusion: Visual inspection and adjustment were necessary for most ROIs. Fast automatic ROI propagation followed by user-driven adjustment appears to be more efficient than labor-intensive de novo drawing. Dose summation using deformable image coregistration was feasible. Biological uncertainties of dose summation strategies warrant further investigation.« less
  • Purpose: The work aims to 1) prove the feasibility of dose painting by numbers (DPBN) in proton therapy with usual contour-driven plan optimization and 2) compare the achieved plan quality to that of rotational IMRT. Methods: For two patients with head and neck cancers, voxel-by-voxel prescription to the target volume (PTV-PET) was calculated from {sup 18} FDG-PET images and converted to contour-based prescription by defining several sub-contours. Treatments were planned with RayStation (RaySearch Laboratories, Sweden) and proton pencil beam scanning modality. In order to determine the optimal plan parameters to approach the DPBN prescription, the effect of the number ofmore » fields, number of sub-contours and use of range shifter were tested separately on each patient. The number of sub-contours were increased from 3 to 11 while the number of fields were set to 3, 5, 7 and 9. Treatment plans were also optimized on two rotational IMRT systems (TomoTherapy and Varian RapidArc) using previously published guidelines. Results: For both patients, more than 99% of the PTV-PET received at least 95% of the prescribed dose while less than 1% of the PTV-PET received more than 105%, which demonstrates the feasibility of the treatment. Neither the use of a range shifter nor the increase of the number of fields had a significant influence on PTV coverage. Plan quality increased when increasing number of fields up to 7 or 9 and slightly decreased for a bigger number of sub-contours. Good OAR sparing is achieved while keeping high plan quality. Finally, proton therapy achieved significantly better plan quality than rotational IMRT. Conclusion: Voxel-by-voxel prescriptions can be approximated accurately in proton therapy using a contour-driven optimization. Target coverage is nearly insensitive to the number of fields and the use of a range shifter. Finally, plan quality assessment confirmed the superiority of proton therapy compared to rotational IMRT.« less