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Dynamics of Tumor Hypoxia in Patients undergoing Radiochemotherapy for Head and Neck Cancer Evaluated with Serial 18F-fluoromisonidazole PET
Proceedings of the 52nd Annual ASTRO Meeting directions are 3.875 mm, 1.25 mm and 3.625 mm, respectively. If the interpolation and filtering are same, the maximum differences among the different similarity measurements are 4.125 mm, 2.875 mm, and 12.375 mm in the three directions respectively. Conclusions: Among these techniques, the method of similarity measurement plays the most important role, while image interpolation technique makes the least difference, with mutual information and normalized mutual information being the best, especially in the SI direction. Nonlinear filtering can makes edges visible by removing noise. Author Disclosure: X. Wu, None; R. Popple, None; J. Fiveash, None; R. Jacob, None; P. Pareek, None; I. Brezovich, None.
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Dynamics of Tumor Hypoxia in Patients undergoing Radiochemotherapy for Head and Neck Cancer Evaluated with Serial 18F-fluoromisonidazole PET
N. Wiedenmann1, M. Hentschel1, S. Bucher1, M. Mix2, S. Adebahr1, C. Offermann1, U. Nestle1, W. Weber2, A. L. Grosu1 1
Department of Radiation Oncology, Freiburg, Germany, 2Department of Nuclear Medicine, Freiburg, Germany
Purpose/Objective(s): Data on the dynamics of tumor hypoxia during treatment is scarce. The purpose of the present study was to noninvasively assess the time course of tumor hypoxia during standard radiochemotherapy in SCC of the head and neck. Materials/Methods: A prospective serial imaging study was conducted in patients undergoing definitive radiochemotherapy (RCTx) for locally advanced head and neck cancer. Radiation treatment was delivered as conformal 3D RT or IMRT (5X2Gy/d, total dose 70 Gy). Cisplatin was administered in week 1, 4, and 7 (100 mg/m2). CT, MRI and 18F-FDG-PET were acquired prior to treatment and MRI was repeated in week 5. Tumor hypoxia was visualized by 18F-fluoromisonidazole PET (F-MISO-PET) at baseline and in treatment week 2 (22 +/-7.5 Gy) and 5 (56 +/-8.6 Gy). Static F-MISO scans were acquired 2.5h p.i. Study endpoints were the visual and quantitative assessment of F-MISO tumor uptake and local tumor control. F-MISO uptake was visually scored from 0 (no hypoxia) to 3 (significant hypoxia). The index of SUVmax in tumors/SUVmean in muscle was calculated for each patient. Mean and median indices for all patients were quantified for the first (pre-treatment), second (week 2) and third (week 5) F-MISO PET investigation. Tumor volumes were determined for FDG PET scans and the coregistered F-MISO scans. For follow-up patients were evaluated clinically and by MRI every 3 months. Results: Sixteen patients were included, undergoing definitive RCTx for locally advanced cancer of the oral cavity (1), oropharynx (7), hypopharynx (5) and larynx (3). T3-stage was present in 5 and T4 in 11 cases. Nodal stage was N2b in 2 and N2c in 14 pts. Mean summed tumor and lymph node volumes per patient were determined by FDG PET as 26.5 +/- 22 ml. The baseline F-MISO examination could be completed by all patients, the second F-MISO scan by 14 of 16 pts and the third by 11 of 16 pts respectively. Visual assessment showed significant pre-treatment tumor hypoxia in 14 of 16 pts. In week 2, marked hypoxia was seen in 6 of 14 pts, and in week 5 in 2 of 11 pts respectively. The mean SUVmax indices decreased from 1.9 (pre-treatment) to 1.6 (wk 2) and 1.3 (wk 5). The median SUVmax indices decreased from 2.0 (pre-treatment) to 1.3 (wk 2) and 1.2 (wk 5). Mean hypoxic tumor volumes declined from 15.8 mL (baseline) to 6.3 mL (wk 2) and 0.4 ml (wk 5). At a mean follow-up time of 6 months local failure or absence of tumor response was observed in 3 pts. No local recurrence was seen when at least one F-MISO scan indicated tumor reoxygenation at the end of treatment. Conclusions: Significant and stable reduction of tumor hypoxia was found in the majority of patients. The current follow-up data indicate a correlation between persistent tumor hypoxia and inferior outcome. Author Disclosure: N. Wiedenmann, None; M. Hentschel, None; S. Bucher, None; M. Mix, None; S. Adebahr, None; C. Offermann, None; U. Nestle, None; W. Weber, None; A.L. Grosu, None.
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Adaptive Radiotherapy for Head and Neck Cancer Patients Treated with IMRT: A Radiobiological Evaluation
L. Marucci, D. D’Alessio, V. Bruzzaniti, L. Strigari, C. Giordano, G. Giovinazzo, P. Pinnaro, S. Marzi Regina Elena Institute, Rome 00144, Italy Purpose/Objective(s): To quantify, using radiobiological parameters, the impact of anatomical changes on expected treatment outcomes. Materials/Methods: Ten patients with advanced loco-regional head-and-neck cancer with no evidence of distant metastasis were enrolled in a prospective study at our Institute. All patients were treated with concomitant chemo-radiotherapy (RT). The prescribed doses were: 70 Gy to the GTV (Gross Tumor Volume), 60 and 54 Gy to the CTV1 (clinical target volume or regions at high risk of microscopic disease) and CTV2 (regions at intermediate risk) respectively. The treatment was delivered with 7 coplanar intensitymodulated fields in 33 fractions, using a simultaneous integrated boost. A CT without contrast was repeated at the end of each week of treatment. The regions of interest (targets, parotids and spinal cord) were manually re-contoured on every CT. The original plan was re-run on the each CT to evaluate the dosimetric changes during the treatment. The TCP (Tumor Control Probability) was calculated using the linear quadratic model of cell survival, with a = 0.39 Gy 1, a/b = 16.3 Gy. The salivary glands NTCP (Normal Tissue Complication Probability) were calculated using the Lyman-Kutcher-Burman (LKB) model. Grade 3 xerostomia was assumed as primary end point, using the Radiation Therapy Oncology Group (RTOG) late toxicity scale. The model parameters were: n = 1, m = 0.45, TD50 = 41.6 Gy at 12 months after RT. An a/b ratio of 3 Gy was assumed to take into account the dose fractionation. Results: GTV decreased on average to 59 ± 18% and 32 ± 16% of the original value, after 3 and 6 weeks of RT respectively. Analogously, CTV70 and CTV60 decreased to 68 ± 16% and 90 ± 9% after 3 weeks of RT, respectively, and to 42 ± 15% and 89 ± 13% after 6 weeks of RT. The mean weight loss during therapy was 7.5Kg (range, 1-13kg). The dose coverage of all targets did not change appreciably during RT. The mean doses varied, on average, no more than 2.5%. Consequently, the TCPGTV was stable during treatment. The parotids, treated as a single paired organ, decreased to 80 ± 13% and 65 ± 14% of the pre-RT volume, after 3 and 6 weeks of RT, respectively. Mean doses slightly increased during RT (5% on average), with a minimum impact on
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Dynamics of Tumor Hypoxia in Patients undergoing Radiochemotherapy for Head and Neck Cancer Evaluated with Serial 18F-fluoromisonidazole PET
N. Wiedenmann1, M. Hentschel1, S. Bucher1, M. Mix2, S. Adebahr1, C. Offermann1, U. Nestle1, W. Weber2, A. L. Grosu1 1
Department of Radiation Oncology, Freiburg, Germany, 2Department of Nuclear Medicine, Freiburg, Germany
Purpose/Objective(s): Data on the dynamics of tumor hypoxia during treatment is scarce. The purpose of the present study was to noninvasively assess the time course of tumor hypoxia during standard radiochemotherapy in SCC of the head and neck. Materials/Methods: A prospective serial imaging study was conducted in patients undergoing definitive radiochemotherapy (RCTx) for locally advanced head and neck cancer. Radiation treatment was delivered as conformal 3D RT or IMRT (5X2Gy/d, total dose 70 Gy). Cisplatin was administered in week 1, 4, and 7 (100 mg/m2). CT, MRI and 18F-FDG-PET were acquired prior to treatment and MRI was repeated in week 5. Tumor hypoxia was visualized by 18F-fluoromisonidazole PET (F-MISO-PET) at baseline and in treatment week 2 (22 +/-7.5 Gy) and 5 (56 +/-8.6 Gy). Static F-MISO scans were acquired 2.5h p.i. Study endpoints were the visual and quantitative assessment of F-MISO tumor uptake and local tumor control. F-MISO uptake was visually scored from 0 (no hypoxia) to 3 (significant hypoxia). The index of SUVmax in tumors/SUVmean in muscle was calculated for each patient. Mean and median indices for all patients were quantified for the first (pre-treatment), second (week 2) and third (week 5) F-MISO PET investigation. Tumor volumes were determined for FDG PET scans and the coregistered F-MISO scans. For follow-up patients were evaluated clinically and by MRI every 3 months. Results: Sixteen patients were included, undergoing definitive RCTx for locally advanced cancer of the oral cavity (1), oropharynx (7), hypopharynx (5) and larynx (3). T3-stage was present in 5 and T4 in 11 cases. Nodal stage was N2b in 2 and N2c in 14 pts. Mean summed tumor and lymph node volumes per patient were determined by FDG PET as 26.5 +/- 22 ml. The baseline F-MISO examination could be completed by all patients, the second F-MISO scan by 14 of 16 pts and the third by 11 of 16 pts respectively. Visual assessment showed significant pre-treatment tumor hypoxia in 14 of 16 pts. In week 2, marked hypoxia was seen in 6 of 14 pts, and in week 5 in 2 of 11 pts respectively. The mean SUVmax indices decreased from 1.9 (pre-treatment) to 1.6 (wk 2) and 1.3 (wk 5). The median SUVmax indices decreased from 2.0 (pre-treatment) to 1.3 (wk 2) and 1.2 (wk 5). Mean hypoxic tumor volumes declined from 15.8 mL (baseline) to 6.3 mL (wk 2) and 0.4 ml (wk 5). At a mean follow-up time of 6 months local failure or absence of tumor response was observed in 3 pts. No local recurrence was seen when at least one F-MISO scan indicated tumor reoxygenation at the end of treatment. Conclusions: Significant and stable reduction of tumor hypoxia was found in the majority of patients. The current follow-up data indicate a correlation between persistent tumor hypoxia and inferior outcome. Author Disclosure: N. Wiedenmann, None; M. Hentschel, None; S. Bucher, None; M. Mix, None; S. Adebahr, None; C. Offermann, None; U. Nestle, None; W. Weber, None; A.L. Grosu, None.
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Adaptive Radiotherapy for Head and Neck Cancer Patients Treated with IMRT: A Radiobiological Evaluation
L. Marucci, D. D’Alessio, V. Bruzzaniti, L. Strigari, C. Giordano, G. Giovinazzo, P. Pinnaro, S. Marzi Regina Elena Institute, Rome 00144, Italy Purpose/Objective(s): To quantify, using radiobiological parameters, the impact of anatomical changes on expected treatment outcomes. Materials/Methods: Ten patients with advanced loco-regional head-and-neck cancer with no evidence of distant metastasis were enrolled in a prospective study at our Institute. All patients were treated with concomitant chemo-radiotherapy (RT). The prescribed doses were: 70 Gy to the GTV (Gross Tumor Volume), 60 and 54 Gy to the CTV1 (clinical target volume or regions at high risk of microscopic disease) and CTV2 (regions at intermediate risk) respectively. The treatment was delivered with 7 coplanar intensitymodulated fields in 33 fractions, using a simultaneous integrated boost. A CT without contrast was repeated at the end of each week of treatment. The regions of interest (targets, parotids and spinal cord) were manually re-contoured on every CT. The original plan was re-run on the each CT to evaluate the dosimetric changes during the treatment. The TCP (Tumor Control Probability) was calculated using the linear quadratic model of cell survival, with a = 0.39 Gy 1, a/b = 16.3 Gy. The salivary glands NTCP (Normal Tissue Complication Probability) were calculated using the Lyman-Kutcher-Burman (LKB) model. Grade 3 xerostomia was assumed as primary end point, using the Radiation Therapy Oncology Group (RTOG) late toxicity scale. The model parameters were: n = 1, m = 0.45, TD50 = 41.6 Gy at 12 months after RT. An a/b ratio of 3 Gy was assumed to take into account the dose fractionation. Results: GTV decreased on average to 59 ± 18% and 32 ± 16% of the original value, after 3 and 6 weeks of RT respectively. Analogously, CTV70 and CTV60 decreased to 68 ± 16% and 90 ± 9% after 3 weeks of RT, respectively, and to 42 ± 15% and 89 ± 13% after 6 weeks of RT. The mean weight loss during therapy was 7.5Kg (range, 1-13kg). The dose coverage of all targets did not change appreciably during RT. The mean doses varied, on average, no more than 2.5%. Consequently, the TCPGTV was stable during treatment. The parotids, treated as a single paired organ, decreased to 80 ± 13% and 65 ± 14% of the pre-RT volume, after 3 and 6 weeks of RT, respectively. Mean doses slightly increased during RT (5% on average), with a minimum impact on
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