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Temporo-spatial Changes of Enlarged Cervical Lymph Nodes During Head and Neck Cancer IMRT Imaged With Daily On-Line Cone-Beam CT
I. J. Radiation Oncology d Biology d Physics
S420
Volume 69, Number 3, Supplement, 2007
analysis was performed, correlating degree of chronic dysphagia with V50, V60, and mean dose of the PCM and larynx. Multivariate analysis was performed to assess correlation of chronic dysphagia with mean CTV1, CTV2, and parotid dose, age, site, T-stage, N-stage, and degree of xerostomia. Results: Mean and median follow-up time were 15 and 14 months (8–34) respectively. There was a statistically significant difference in degree of chronic dysphagia with increasing mean dose to the PCM (p \ 0.001). V50 and V60 of the PCM were both significantly correlated with degree of dysphagia (p = 0.002, p = 0.004). V50, V60, and mean dose of the larynx were not significantly correlated with dysphagia. There was no significant correlation between chronic dysphagia and mean dose to CTV1, CTV2, parotid dose, xerostomia, age, site, T-stage, or N-stage (Table). Conclusions: A positive clinical correlation exists between PCM dose and chronic dysphagia that warrants special attention to this structure when designing IMRT plans. With a narrow dosimetric range for significant differences in long term dysphagia, strong consideration should be made for limiting excessive dose to the PCM when implementing IMRT dose constraints. We recommend striving to maintain a mean constrictor dose #60 Gy and V60 # 60%. Table 1 Pharyngeal Constrictors (mean dose–Gy)
Supraglottic and Glottic Larynx (mean dose–Gy)
V50 Pharyngeal V60 Pharyngeal Constrictors Constrictors (%) (%) V50 Larynx (%)
Grade 0 dysphagia 58.1 Gy (54.2–61.8) 55.4 Gy (47.7–62.4) 83% (60–98) Grade I dysphagia 62.5 Gy (61.2–63.6) 64.2 Gy (56.4–71.1) 93% (85–99)
47% (22–70) 69% (58–80)
76% (25–100) 98% (95–100)
Grade II dysphagia 64.2 Gy (62.1–65.9) 57.7 Gy (54.3–64.0) 95% (91–98) Grade III–IV 66.4 Gy (63.4–70.2) 62.3 Gy (54.1–70.3) 98% (95–100)
68% (56–78) 85% (60–100)
85% (60–100) 95% (78–100)
dysphagia p value
0.004
\0.001
0.65
0.002
0.61
V60 Larynx
Chronic Xerostomia (grade)
Parotid glands (mean dose–Gy)
22% (1–61) 24.7 Gy (21.8–27.0) I (8/8) 69% (13–100) 23.9 Gy (21.2–26.3) 0 (1/8) I (6/8) II (1/8) 35% (13–73) 24.6 Gy (22.8–27.4) I (6/7) II (1/7) 65% (3–100) 23.3 Gy (20.3–25.3) I (7/7) 0.38
0.43
0.81
Author Disclosure: A.W. Suen, None; P.Y. Chen, None; K. Chao, None; A.P. Galerani, None; A.A. Martinez, None.
2389
Association Between Esophageal Stricture Formation and Dose Volume Histogram (DVH) Parameters in Oropharyngeal Cancer Patients Treated With Intensity Modulated Radiation Therapy (IMRT)
S. Both, P. R. Dutta, V. Bar Ad, H. Quon Dept. of Radiation Oncology, Philadelphia, PA Purpose/Objective(s): Treatment of head and neck malignancies with IMRT allows careful sparing of normal structures while providing adequate coverage to target volumes. However, patients (pts) treated for malignancies of the oropharynx can develop esophageal strictures requiring endoscopic dilation. Since the correlation between dose and esophageal toxicity is not well established, this relationship requires further investigation. Materials/Methods: In this retrospective study, the medical records of 69 consecutive pts with oropharyngeal cancers who underwent radiotherapy from March, 2004 to April, 2006 were reviewed. Patients requiring esophageal dilation were identified. IMRT planning was performed to deliver a concomitant boost technique, using the Oncentra MasterPlan V.1.4.1.3 treatment planning system, based on our protocol (definitive radiotherapy: 57.6, 66, and 70.4 Gy to the LRCTV, HRCTV and GTV, or postoperative radiotherapy: 54, 63, and 66 Gy to the LRCTV, HRCTV and GTV, respectively). The minimum follow-up period was 1 year from the end of treatment. Dose to the proximal esophagus was calculated and compared with published dose-response parameters: median dose (D50) and the dose to 80% of the volume (D80). Pts were analyzed in regards to these DVH parameters. Results: A total of 6 pts (8.7%) required 1 to 3 endoscopic esophageal dilations for stricture formation within the proximal esophagus. All of these pts were staged with IVa disease at the time of diagnosis; 3 pts underwent surgical resection and treated postoperatively, and half treated with definitive radiation. All 6 pts were treated with concurrent chemotherapy. The median time to the first dilation in these pts was at 10 months, (range: 4–13 months) from the end of treatment. For the proximal esophagus, the median ± std dev for the D50 and the D80 were found to be 51.4 ± 6.7 Gy and 49.5 ± 6.5 Gy, respectively. Conclusions: Published data reported that for 3D-CRT mean doses of 60 Gy to the proximal 5 cm of the esophagus should be used as a reference. In the proximal 2 cm of the esophagus, D80 . 60 Gy correlated with increased esophageal toxicity. The use of mean dose concept in IMRT is debatable due to its high dose-heterogeneity index. Our data suggest that for IMRT a lower D80 of 49.5 ± 6.5 Gy is sufficient to induce esophageal strictures requiring endoscopic dilation. In addition, our DVH analysis revealed that the D50 was similar with D80 for patients experiencing esophageal toxicity. Therefore, both parameters may be useful DVH indicators for predicting esophageal toxicity in patients treated with IMRT. Author Disclosure: S. Both, None; P.R. Dutta, None; V. Bar Ad, None; H. Quon, None.
2390
Temporo-spatial Changes of Enlarged Cervical Lymph Nodes During Head and Neck Cancer IMRT Imaged With Daily On-Line Cone-Beam CT
D. Hwang1,2, M. Vakilha1, S. Breen1,2, C. Thomas1, L. Dawson1,2, J. Ringash1,2, J. Kim1,2, B. Cummings1,2, B. O’Sullivan1,2, J. Waldron1,2 1
Princess Margaret Hospital, Toronto, ON, Canada, 2University of Toronto, Toronto, ON, Canada
Purpose/Objective(s): Head and neck cancer intensity modulated radiation therapy (IMRT) requires reproducible positioning of target volumes. The purpose of this study is to measure the changes in position and volume of enlarged cervical lymph nodes due to weight loss or response to IMRT with daily kV cone-beam CTs (CBCTs) obtained during IMRT. Materials/Methods: 15 patients with a diagnosis of squamous cell carcinoma of head and neck and at least one enlarged discrete lymph node .2 cm on CT were studied. Each patient received IMRT with curative intent (25 to 40 fractions over 4 to 7 weeks)
Proceedings of the 49th Annual ASTRO Meeting using a 5 mm PTV. Eleven patients received concurrent chemotherapy. All patients were imaged daily with cone-beam CT (Elekta, Crawley, UK). Images were aligned to the planning CT by registration of bony anatomy adjacent to the primary disease site. Isocenter displacements .3 mm were corrected and patients were re-imaged; any rotations were converted to translational corrections. The cervical lymph nodes were independently contoured on the CBCT data sets for each fraction by two radiation oncologists. Daily changes in volume and position of the nodes on CBCT relative to the same node on planning CT were measured over the course of treatment. The location of each lymph node and its associated CTV (5-mm expansion of the node) for each treatment fraction were compared to the nodal PTV (5 mm expansion of CTV) for that node. The percentage of daily cone beam CTVs encompassed by PTVs of 2-, 5-, and 6-mm margins (PTV2 mm, PTV5 mm, PTV6 mm) was calculated for the entire treatment course. Results: All patients completed IMRT as planned, and 529 pre-treatment cone beam images were evaluated. The mean nodal volume reduction was 63% (range 14.8–92.3, SD 25.3%) and mean weight loss was 7.6%. The mean movement of the centroid of the nodes relative to the node at planning was 0.36 cm towards the midline (range 1.56 cm medially to 0.95 cm laterally), 0.02 cm inferiorly (range 1.02 superior to 1.92 cm inferior) and 0.02 cm in the anterior direction (range 1.6 cm posterior to 1.27 cm anterior). Volumes drawn by the two oncologists were not substantially different. PTV5 mm encompassed 67% to 100% of the summed volumes of daily CTVs (mean 92%, SD 7%) for the first oncologist, and 75% to 100% for the second (mean 93%, SD 7%). PTV2 mm had a mean encompassing percentage of 77%, which increased to 94.2% for PTV6 mm. Conclusions: Substantial positional and volumetric changes occur in enlarged lymph nodes during a course of head and neck cancer IMRT. Whilst all nodes decreased in size, movement was observed systematically in the medial direction even following isocenter correction. In some cases the range of movement daily shifted the CTV out of the PTV for part of the radiotherapy course. The potential underdosage of these nodes and relationship to clinical response will be investigated in future studies. Author Disclosure: D. Hwang, None; M. Vakilha, None; S. Breen, None; C. Thomas, None; L. Dawson, None; J. Ringash, None; J. Kim, None; B. Cummings, None; B. O’Sullivan, None; J. Waldron, None.
2391
IMRT for Nasopharyngeal Cancer: The Washington University in St. Louis Experience
D. M. Macdonald, I. M. El Naqa, A. J. Hope, J. O. Deasy, W. L. Thorstad Washington University School of Medicine, St. Louis, MO Purpose/Objective(s): To review our institutional experience using intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma. Materials/Methods: Thirty patients with nasopharyngeal cancer were treated at Washington University in St. Louis with definitive IMRT between 1997 and 2005. Median age at diagnosis was 51 years; 87% of patients were male, 13% female; 67% were white, 23% black, and 10% Asian. Disease was stage I in 7%, stage II in 13%, stage III in 20%, and stage IV in 60%; WHO grade was I in 10%, II in 30%, III in 57% and unspecified in 3%. The gross tumor areas plus margins received 69–72 Gy in 32–39 fractions; clinically uninvolved areas at risk for recurrence received 59.4–63 Gy in 33–35 fractions. The low neck received 46–59.4 Gy via a matched AP field (60%), or contiguous IMRT (40%). No patient received a brachytherapy boost or more than one fraction per day. 93% of patients received platinum-based chemotherapy concurrently with radiation therapy. Acute and late treatment effects were graded according to RTOG criteria. We used the Kaplan-Meier method to calculate overall survival, distant metastasis-free probability, and local progression-free probability. Results: At a median follow-up of 37 months (range 13–94 months) no patients have experienced failure at the primary tumor site. One patient experienced an isolated regional failure in the upper neck, one patient developed a regional failure in the low neck and distant metastasis simultaneously, and six patients developed distant metastasis despite locoregional control. Overall survival, distant metastasis-free probability and local progression-free probability at three years were estimated to be 81%, 76%, and 93%, respectively (Figure). Grade 3 or greater acute toxicity was noted in 77% of patients. Most common were mucus membrane toxicity (57% of patients), and nutritional compromise requiring placement of a gastrostomy tube (67% of patients). Late toxicities are emerging, including radiographic findings concerning for temporal lobe necrosis in three patients (10%) at 24, 30, and 36 months following completion of therapy. All three patients remain asymptomatic; no pathologic confirmation of radiation necrosis exists to date. Conclusions: This experience confirms other reports of excellent locoregional control with IMRT for nasopharyngeal carcinoma. Acute toxicity is significant requiring appropriate supportive care. Late toxicities continue to develop more than two years following therapy, mandating careful long-term follow-up.
Author Disclosure: D.M. Macdonald, None; I.M. El Naqa, None; A.J. Hope, None; J.O. Deasy, None; W.L. Thorstad, None.
S421
S420
Volume 69, Number 3, Supplement, 2007
analysis was performed, correlating degree of chronic dysphagia with V50, V60, and mean dose of the PCM and larynx. Multivariate analysis was performed to assess correlation of chronic dysphagia with mean CTV1, CTV2, and parotid dose, age, site, T-stage, N-stage, and degree of xerostomia. Results: Mean and median follow-up time were 15 and 14 months (8–34) respectively. There was a statistically significant difference in degree of chronic dysphagia with increasing mean dose to the PCM (p \ 0.001). V50 and V60 of the PCM were both significantly correlated with degree of dysphagia (p = 0.002, p = 0.004). V50, V60, and mean dose of the larynx were not significantly correlated with dysphagia. There was no significant correlation between chronic dysphagia and mean dose to CTV1, CTV2, parotid dose, xerostomia, age, site, T-stage, or N-stage (Table). Conclusions: A positive clinical correlation exists between PCM dose and chronic dysphagia that warrants special attention to this structure when designing IMRT plans. With a narrow dosimetric range for significant differences in long term dysphagia, strong consideration should be made for limiting excessive dose to the PCM when implementing IMRT dose constraints. We recommend striving to maintain a mean constrictor dose #60 Gy and V60 # 60%. Table 1 Pharyngeal Constrictors (mean dose–Gy)
Supraglottic and Glottic Larynx (mean dose–Gy)
V50 Pharyngeal V60 Pharyngeal Constrictors Constrictors (%) (%) V50 Larynx (%)
Grade 0 dysphagia 58.1 Gy (54.2–61.8) 55.4 Gy (47.7–62.4) 83% (60–98) Grade I dysphagia 62.5 Gy (61.2–63.6) 64.2 Gy (56.4–71.1) 93% (85–99)
47% (22–70) 69% (58–80)
76% (25–100) 98% (95–100)
Grade II dysphagia 64.2 Gy (62.1–65.9) 57.7 Gy (54.3–64.0) 95% (91–98) Grade III–IV 66.4 Gy (63.4–70.2) 62.3 Gy (54.1–70.3) 98% (95–100)
68% (56–78) 85% (60–100)
85% (60–100) 95% (78–100)
dysphagia p value
0.004
\0.001
0.65
0.002
0.61
V60 Larynx
Chronic Xerostomia (grade)
Parotid glands (mean dose–Gy)
22% (1–61) 24.7 Gy (21.8–27.0) I (8/8) 69% (13–100) 23.9 Gy (21.2–26.3) 0 (1/8) I (6/8) II (1/8) 35% (13–73) 24.6 Gy (22.8–27.4) I (6/7) II (1/7) 65% (3–100) 23.3 Gy (20.3–25.3) I (7/7) 0.38
0.43
0.81
Author Disclosure: A.W. Suen, None; P.Y. Chen, None; K. Chao, None; A.P. Galerani, None; A.A. Martinez, None.
2389
Association Between Esophageal Stricture Formation and Dose Volume Histogram (DVH) Parameters in Oropharyngeal Cancer Patients Treated With Intensity Modulated Radiation Therapy (IMRT)
S. Both, P. R. Dutta, V. Bar Ad, H. Quon Dept. of Radiation Oncology, Philadelphia, PA Purpose/Objective(s): Treatment of head and neck malignancies with IMRT allows careful sparing of normal structures while providing adequate coverage to target volumes. However, patients (pts) treated for malignancies of the oropharynx can develop esophageal strictures requiring endoscopic dilation. Since the correlation between dose and esophageal toxicity is not well established, this relationship requires further investigation. Materials/Methods: In this retrospective study, the medical records of 69 consecutive pts with oropharyngeal cancers who underwent radiotherapy from March, 2004 to April, 2006 were reviewed. Patients requiring esophageal dilation were identified. IMRT planning was performed to deliver a concomitant boost technique, using the Oncentra MasterPlan V.1.4.1.3 treatment planning system, based on our protocol (definitive radiotherapy: 57.6, 66, and 70.4 Gy to the LRCTV, HRCTV and GTV, or postoperative radiotherapy: 54, 63, and 66 Gy to the LRCTV, HRCTV and GTV, respectively). The minimum follow-up period was 1 year from the end of treatment. Dose to the proximal esophagus was calculated and compared with published dose-response parameters: median dose (D50) and the dose to 80% of the volume (D80). Pts were analyzed in regards to these DVH parameters. Results: A total of 6 pts (8.7%) required 1 to 3 endoscopic esophageal dilations for stricture formation within the proximal esophagus. All of these pts were staged with IVa disease at the time of diagnosis; 3 pts underwent surgical resection and treated postoperatively, and half treated with definitive radiation. All 6 pts were treated with concurrent chemotherapy. The median time to the first dilation in these pts was at 10 months, (range: 4–13 months) from the end of treatment. For the proximal esophagus, the median ± std dev for the D50 and the D80 were found to be 51.4 ± 6.7 Gy and 49.5 ± 6.5 Gy, respectively. Conclusions: Published data reported that for 3D-CRT mean doses of 60 Gy to the proximal 5 cm of the esophagus should be used as a reference. In the proximal 2 cm of the esophagus, D80 . 60 Gy correlated with increased esophageal toxicity. The use of mean dose concept in IMRT is debatable due to its high dose-heterogeneity index. Our data suggest that for IMRT a lower D80 of 49.5 ± 6.5 Gy is sufficient to induce esophageal strictures requiring endoscopic dilation. In addition, our DVH analysis revealed that the D50 was similar with D80 for patients experiencing esophageal toxicity. Therefore, both parameters may be useful DVH indicators for predicting esophageal toxicity in patients treated with IMRT. Author Disclosure: S. Both, None; P.R. Dutta, None; V. Bar Ad, None; H. Quon, None.
2390
Temporo-spatial Changes of Enlarged Cervical Lymph Nodes During Head and Neck Cancer IMRT Imaged With Daily On-Line Cone-Beam CT
D. Hwang1,2, M. Vakilha1, S. Breen1,2, C. Thomas1, L. Dawson1,2, J. Ringash1,2, J. Kim1,2, B. Cummings1,2, B. O’Sullivan1,2, J. Waldron1,2 1
Princess Margaret Hospital, Toronto, ON, Canada, 2University of Toronto, Toronto, ON, Canada
Purpose/Objective(s): Head and neck cancer intensity modulated radiation therapy (IMRT) requires reproducible positioning of target volumes. The purpose of this study is to measure the changes in position and volume of enlarged cervical lymph nodes due to weight loss or response to IMRT with daily kV cone-beam CTs (CBCTs) obtained during IMRT. Materials/Methods: 15 patients with a diagnosis of squamous cell carcinoma of head and neck and at least one enlarged discrete lymph node .2 cm on CT were studied. Each patient received IMRT with curative intent (25 to 40 fractions over 4 to 7 weeks)
Proceedings of the 49th Annual ASTRO Meeting using a 5 mm PTV. Eleven patients received concurrent chemotherapy. All patients were imaged daily with cone-beam CT (Elekta, Crawley, UK). Images were aligned to the planning CT by registration of bony anatomy adjacent to the primary disease site. Isocenter displacements .3 mm were corrected and patients were re-imaged; any rotations were converted to translational corrections. The cervical lymph nodes were independently contoured on the CBCT data sets for each fraction by two radiation oncologists. Daily changes in volume and position of the nodes on CBCT relative to the same node on planning CT were measured over the course of treatment. The location of each lymph node and its associated CTV (5-mm expansion of the node) for each treatment fraction were compared to the nodal PTV (5 mm expansion of CTV) for that node. The percentage of daily cone beam CTVs encompassed by PTVs of 2-, 5-, and 6-mm margins (PTV2 mm, PTV5 mm, PTV6 mm) was calculated for the entire treatment course. Results: All patients completed IMRT as planned, and 529 pre-treatment cone beam images were evaluated. The mean nodal volume reduction was 63% (range 14.8–92.3, SD 25.3%) and mean weight loss was 7.6%. The mean movement of the centroid of the nodes relative to the node at planning was 0.36 cm towards the midline (range 1.56 cm medially to 0.95 cm laterally), 0.02 cm inferiorly (range 1.02 superior to 1.92 cm inferior) and 0.02 cm in the anterior direction (range 1.6 cm posterior to 1.27 cm anterior). Volumes drawn by the two oncologists were not substantially different. PTV5 mm encompassed 67% to 100% of the summed volumes of daily CTVs (mean 92%, SD 7%) for the first oncologist, and 75% to 100% for the second (mean 93%, SD 7%). PTV2 mm had a mean encompassing percentage of 77%, which increased to 94.2% for PTV6 mm. Conclusions: Substantial positional and volumetric changes occur in enlarged lymph nodes during a course of head and neck cancer IMRT. Whilst all nodes decreased in size, movement was observed systematically in the medial direction even following isocenter correction. In some cases the range of movement daily shifted the CTV out of the PTV for part of the radiotherapy course. The potential underdosage of these nodes and relationship to clinical response will be investigated in future studies. Author Disclosure: D. Hwang, None; M. Vakilha, None; S. Breen, None; C. Thomas, None; L. Dawson, None; J. Ringash, None; J. Kim, None; B. Cummings, None; B. O’Sullivan, None; J. Waldron, None.
2391
IMRT for Nasopharyngeal Cancer: The Washington University in St. Louis Experience
D. M. Macdonald, I. M. El Naqa, A. J. Hope, J. O. Deasy, W. L. Thorstad Washington University School of Medicine, St. Louis, MO Purpose/Objective(s): To review our institutional experience using intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma. Materials/Methods: Thirty patients with nasopharyngeal cancer were treated at Washington University in St. Louis with definitive IMRT between 1997 and 2005. Median age at diagnosis was 51 years; 87% of patients were male, 13% female; 67% were white, 23% black, and 10% Asian. Disease was stage I in 7%, stage II in 13%, stage III in 20%, and stage IV in 60%; WHO grade was I in 10%, II in 30%, III in 57% and unspecified in 3%. The gross tumor areas plus margins received 69–72 Gy in 32–39 fractions; clinically uninvolved areas at risk for recurrence received 59.4–63 Gy in 33–35 fractions. The low neck received 46–59.4 Gy via a matched AP field (60%), or contiguous IMRT (40%). No patient received a brachytherapy boost or more than one fraction per day. 93% of patients received platinum-based chemotherapy concurrently with radiation therapy. Acute and late treatment effects were graded according to RTOG criteria. We used the Kaplan-Meier method to calculate overall survival, distant metastasis-free probability, and local progression-free probability. Results: At a median follow-up of 37 months (range 13–94 months) no patients have experienced failure at the primary tumor site. One patient experienced an isolated regional failure in the upper neck, one patient developed a regional failure in the low neck and distant metastasis simultaneously, and six patients developed distant metastasis despite locoregional control. Overall survival, distant metastasis-free probability and local progression-free probability at three years were estimated to be 81%, 76%, and 93%, respectively (Figure). Grade 3 or greater acute toxicity was noted in 77% of patients. Most common were mucus membrane toxicity (57% of patients), and nutritional compromise requiring placement of a gastrostomy tube (67% of patients). Late toxicities are emerging, including radiographic findings concerning for temporal lobe necrosis in three patients (10%) at 24, 30, and 36 months following completion of therapy. All three patients remain asymptomatic; no pathologic confirmation of radiation necrosis exists to date. Conclusions: This experience confirms other reports of excellent locoregional control with IMRT for nasopharyngeal carcinoma. Acute toxicity is significant requiring appropriate supportive care. Late toxicities continue to develop more than two years following therapy, mandating careful long-term follow-up.
Author Disclosure: D.M. Macdonald, None; I.M. El Naqa, None; A.J. Hope, None; J.O. Deasy, None; W.L. Thorstad, None.
S421