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Title: Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer

Abstract

Purpose: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. Methods and Materials: A Phase I clinical trial was designed to escalate the dose limited to the [{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography ({sup 18}F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. Results: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-yearmore » local control at 85% and 87% (p n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted {sup 18}F-FDG-PET-delineated region. Conclusions: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.« less

Authors:
 [1];  [2];  [2];  [2];  [2];  [2];  [2];  [3];  [3];  [2];  [2];  [4];  [5];  [6];  [7];  [2]
  1. Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium). E-mail: indira@krtkg1.ugent.be
  2. Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)
  3. Department of Radiation Oncology and Center for Molecular Imaging and Experimental Radiotherapy, Universite Catholique de Louvain, St.-Luc University Hospital, Brussels (Belgium)
  4. (Belgium)
  5. Department of Radiology, Ghent University Hospital, Ghent (Belgium)
  6. Department of Head and Neck Surgery, Ghent University Hospital, Ghent (Belgium)
  7. Department of Medical Physics, Ghent University, Ghent (Belgium)
Publication Date:
OSTI Identifier:
20951623
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.2006.12.070; PII: S0360-3016(07)00096-X; 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; CARCINOMAS; CLINICAL TRIALS; DEATH; FLUORINE 18; GLUCOSE; HEAD; NECK; PATIENTS; POSITRON COMPUTED TOMOGRAPHY; RADIATION DOSES; RADIOTHERAPY; TOXICITY

Citation Formats

Madani, Indira, Duthoy, Wim, Derie, Cristina R.N., De Gersem, Werner Ir., Boterberg, Tom, Saerens, Micky, Jacobs, Filip Ir., Gregoire, Vincent, Lonneux, Max, Vakaet, Luc, Vanderstraeten, Barbara, Department of Medical Physics, Ghent University, Ghent, Bauters, Wouter, Bonte, Katrien, Thierens, Hubert, and Neve, Wilfried de. Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.12.070.
Madani, Indira, Duthoy, Wim, Derie, Cristina R.N., De Gersem, Werner Ir., Boterberg, Tom, Saerens, Micky, Jacobs, Filip Ir., Gregoire, Vincent, Lonneux, Max, Vakaet, Luc, Vanderstraeten, Barbara, Department of Medical Physics, Ghent University, Ghent, Bauters, Wouter, Bonte, Katrien, Thierens, Hubert, & Neve, Wilfried de. Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer. United States. doi:10.1016/j.ijrobp.2006.12.070.
Madani, Indira, Duthoy, Wim, Derie, Cristina R.N., De Gersem, Werner Ir., Boterberg, Tom, Saerens, Micky, Jacobs, Filip Ir., Gregoire, Vincent, Lonneux, Max, Vakaet, Luc, Vanderstraeten, Barbara, Department of Medical Physics, Ghent University, Ghent, Bauters, Wouter, Bonte, Katrien, Thierens, Hubert, and Neve, Wilfried de. Tue . "Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer". United States. doi:10.1016/j.ijrobp.2006.12.070.
@article{osti_20951623,
title = {Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer},
author = {Madani, Indira and Duthoy, Wim and Derie, Cristina R.N. and De Gersem, Werner Ir. and Boterberg, Tom and Saerens, Micky and Jacobs, Filip Ir. and Gregoire, Vincent and Lonneux, Max and Vakaet, Luc and Vanderstraeten, Barbara and Department of Medical Physics, Ghent University, Ghent and Bauters, Wouter and Bonte, Katrien and Thierens, Hubert and Neve, Wilfried de},
abstractNote = {Purpose: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. Methods and Materials: A Phase I clinical trial was designed to escalate the dose limited to the [{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography ({sup 18}F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. Results: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted {sup 18}F-FDG-PET-delineated region. Conclusions: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.},
doi = {10.1016/j.ijrobp.2006.12.070},
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: Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTV{sub h}) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTV{sub h} increases the tumor control probability. This study examined the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ({sup 18}F-FMISO PET/CT)-guided IMRT with the goal of maximally escalating the dose to radioresistant hypoxic zones in a cohort of head and neck cancer (HNC) patients. Methods and Materials: {sup 18}F-FMISO wasmore » administered intravenously for PET imaging. The CT simulation, fluorodeoxyglucose PET/CT, and {sup 18}F-FMISO PET/CT scans were co-registered using the same immobilization methods. The tumor boundaries were defined by clinical examination and available imaging studies, including fluorodeoxyglucose PET/CT. Regions of elevated {sup 18}F-FMISO uptake within the fluorodeoxyglucose PET/CT GTV were targeted for an IMRT boost. Additional targets and/or normal structures were contoured or transferred to treatment planning to generate {sup 18}F-FMISO PET/CT-guided IMRT plans. Results: The heterogeneous distribution of {sup 18}F-FMISO within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing {sup 18}F-FMISO PET/CT-guided IMRT for 10 HNC patients achieved 84 Gy to the GTV{sub h} and 70 Gy to the GTV, without exceeding the normal tissue tolerance. We also attempted to deliver 105 Gy to the GTV{sub h} for 2 patients and were successful in 1, with normal tissue sparing. Conclusion: It was feasible to dose escalate the GTV{sub h} to 84 Gy in all 10 patients and in 1 patient to 105 Gy without exceeding the normal tissue tolerance. This information has provided important data for subsequent hypoxia-guided IMRT trials with the goal of further improving locoregional control in HNC patients.« less
  • Purpose: Magnetic resonance imaging/diffusion weighted-imaging (MRI/DWI)-guided high-dose-rate (HDR) brachytherapy and {sup 18}F-fluorodeoxyglucose (FDG) — positron emission tomography/computed tomography (PET/CT)-guided intensity modulated radiation therapy (IMRT) for the definitive treatment of cervical cancer is a novel treatment technique. The purpose of this study was to report our analysis of dose-volume parameters predicting gross tumor volume (GTV) control. Methods and Materials: We analyzed the records of 134 patients with International Federation of Gynecology and Obstetrics stages IB1-IVB cervical cancer treated with combined MRI-guided HDR and IMRT from July 2009 to July 2011. IMRT was targeted to the metabolic tumor volume and lymph nodesmore » by use of FDG-PET/CT simulation. The GTV for each HDR fraction was delineated by use of T2-weighted or apparent diffusion coefficient maps from diffusion-weighted sequences. The D100, D90, and Dmean delivered to the GTV from HDR and IMRT were summed to EQD2. Results: One hundred twenty-five patients received all irradiation treatment as planned, and 9 did not complete treatment. All 134 patients are included in this analysis. Treatment failure in the cervix occurred in 24 patients (18.0%). Patients with cervix failures had a lower D100, D90, and Dmean than those who did not experience failure in the cervix. The respective doses to the GTV were 41, 58, and 136 Gy for failures compared with 67, 99, and 236 Gy for those who did not experience failure (P<.001). Probit analysis estimated the minimum D100, D90, and Dmean doses required for ≥90% local control to be 69, 98, and 260 Gy (P<.001). Conclusions: Total dose delivered to the GTV from combined MRI-guided HDR and PET/CT-guided IMRT is highly correlated with local tumor control. The findings can be directly applied in the clinic for dose adaptation to maximize local control.« less
  • Purpose: Omitting elective nodal irradiation from planning target volumes does not compromise outcomes in patients with non-small-cell lung cancer, but whether the same is true for those with limited-stage small-cell lung cancer (LS-SCLC) is unknown. Therefore, in the present study, we sought to determine the clinical outcomes and the frequency of elective nodal failure in patients with LS-SCLC staged using positron emission tomography/computed tomography and treated with involved-field intensity-modulated radiotherapy. Methods and Materials: Between 2005 and 2008, 60 patients with LS-SCLC at our institution underwent disease staging using positron emission tomography/computed tomography before treatment using an intensity-modulated radiotherapy plan inmore » which elective nodal irradiation was intentionally omitted from the planning target volume (mode and median dose, 45 Gy in 30 fractions; range, 40.5 Gy in 27 fractions to 63.8 Gy in 35 fractions). In most cases, concurrent platinum-based chemotherapy was administered. We retrospectively reviewed the clinical outcomes to determine the overall survival, relapse-free survival, and failure patterns. Elective nodal failure was defined as recurrence in initially uninvolved hilar, mediastinal, or supraclavicular nodes. Survival was assessed using the Kaplan-Meier method. Results: The median age of the study patients at diagnosis was 63 years (range, 39-86). The median follow-up duration was 21 months (range, 4-58) in all patients and 26 months (range, 4-58) in the survivors. The 2-year actuarial overall survival and relapse-free survival rate were 58% and 43%, respectively. Of the 30 patients with recurrence, 23 had metastatic disease and 7 had locoregional failure. We observed only one isolated elective nodal failure. Conclusions: To our knowledge, this is the first study to examine the outcomes in patients with LS-SCLC staged with positron emission tomography/computed tomography and treated with definitive intensity-modulated radiotherapy. In these patients, elective nodal irradiation can be safely omitted from the planning target volume for the purposes of dose escalation and toxicity reduction.« less
  • To evaluate the change in volume and movement of the parotid gland measured by serial contrast-enhanced computed tomography scans in patients with head and neck cancer treated with parotid-sparing intensity-modulated radiotherapy (IMRT). A prospective study was performed on 13 patients with head and neck cancer undergoing dose-painted IMRT to 69.96 Gy in 33 fractions. Serial computed tomography scans were performed at baseline, weeks 2, 4, and 6 of radiotherapy (RT), and at 6 weeks post-RT. The parotid volume was contoured at each scan, and the movement of the medial and lateral borders was measured. The patient's body weight was recordedmore » at each corresponding week during RT. Regression analyses were performed to ascertain the rate of change during treatment as a percent change per fraction in parotid volume and distance relative to baseline. The mean parotid volume decreased by 37.3% from baseline to week 6 of RT. The overall rate of change in parotid volume during RT was−1.30% per fraction (−1.67% and−0.91% per fraction in≥31 Gy and<31 Gy mean planned parotid dose groups, respectively, p = 0.0004). The movement of parotid borders was greater in the≥31 Gy mean parotid dose group compared with the<31 Gy group (0.22% per fraction and 0.14% per fraction for the lateral border and 0.19% per fraction and 0.06% per fraction for the medial border, respectively). The median change in body weight was−7.4% (range, 0.75% to−17.5%) during RT. A positive correlation was noted between change in body weight and parotid volume during the course of RT (Spearman correlation coefficient, r = 0.66, p<0.01). Head and neck IMRT results in a volume loss of the parotid gland, which is related to the planned parotid dose, and the patient's weight loss during RT.« less
  • Purpose: To quantify changes in fluorodeoxyglucose (FDG)-avid tumor volume on positron emission tomography/computed tomography (PET/CT) during the course of radiation therapy and examine its potential use in adaptive radiotherapy for tumor dose escalation or normal tissue sparing in patients with non-small-cell lung cancer (NSCLC). Methods and Materials: As part of a pilot study, patients with Stage I-III NSCLC underwent FDG-PET/CT before radiotherapy (RT) and in mid-RT (after 40-50 Gy). Gross tumor volumes were contoured on CT and PET scans obtained before and during RT. Three-dimensional conformal RT plans were generated for each patient, first using only pretreatment CT scans. Mid-RTmore » PET volumes were then used to design boost fields. Results: Fourteen patients with FDG-avid tumors were assessed. Two patients had a complete metabolic response, and 2 patients had slightly increased FDG uptake in the adjacent lung tissue. Mid-RT PET scans were useful in the 10 remaining patients. Mean decreases in CT and PET tumor volumes were 26% (range, +15% to -75%) and 44% (range, +10% to -100%), respectively. Designing boosts based on mid-RT PET allowed for a meaningful dose escalation of 30-102 Gy (mean, 58 Gy) or a reduction in normal tissue complication probability (NTCP) of 0.4-3% (mean, 2%) in 5 of 6 patients with smaller yet residual tumor volumes. Conclusions: Tumor metabolic activity and volume can change significantly after 40-50 Gy of RT. Using mid-RT PET volumes, tumor dose can be significantly escalated or NTCP reduced. Clinical studies evaluating patient outcome after PET-based adaptive RT are ongoing.« less