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The Predictive Value of Degree of PTV-OAR Overlap on Achieving Parotid Dose Constraints in Head and Neck Simultaneous Integrated Boost-Intensity Modulated Radiation Therapy (SIB-IMRT)
Proceedings of the 49th Annual ASTRO Meeting
2470
Self-Assessment of Oral Mucositis by Patients During Radio(chemo)therapy for Head and Neck Tumors Using a Visual Analogue Scale
E. Doerr, W. Doerr, T. Herrmann University of Technology Dresden, Dresden, Germany Purpose/Objective(s): Oral Mucositis is a frequent and severe early side effect during radio(chemo)therapy for advanced headand-neck cancer, which often necessitates interruption of the treatment. In the present investigation, self-assessment of the oral cavity by the patients using a visual analogue scale (VAS) was compared to mucositis scores according to the RTOG/EORTC classification system. Materials/Methods: A total of 366 patients with head-and-neck tumours receiving a dose $40 Gy to the oral mucosa were included in the analysis, who were part of a mouth care study comparing dexpanthenol vs. water mouth washes. In the latter investigation, no differences between the study arms and hence, the data could be pooled. Treatment protocols comprised conventional fractionation, hyperfractionation and a combination of both radiochemotherapy. Informed consent was provided by all patients. Professional mouth care including intensive mouth washes with water was performed once daily. In addition to these obligatory procedures, repeated mouth washes with sage tea were recommended. Scoring of mucositis by the investigators according to the RTOG/EORTC-system was done daily. For weekly self-assessment of the oral cavity by the patients, a visual analogue scale (VAS) was applied, in which the patient marks the evaluation of the oral cavity between ‘‘very poor’’ and ‘‘excellent’’. Quantitation is performed according to the location of the patient’s mark as a number between 0 and 10. Results: VAS analysis at the onset of the treatment yielded a significantly lower value of 7.3 ± 0.1 for those patients who subsequently developed mucositis grade 3, compared to 8.2 ± 0.2 for patients without subsequent confluent mucositis. During the treatment, VAS-values significantly decreased; the initial difference between both groups remained nearly constant. From the third treatment week, the subjective VAS-values were significantly lower in those patients that were scored with confluent oral mucositis. Conclusions: Objective scoring according to RTOG/EORTC clearly mirrores the subjective assessment of the patients; the agreement indicates that mucositis significantly impacts on the patients’ quality of life. The value of professional mouth care is un-questioned, as all patients were compliant and no mucositis-associated treatment interruptions occurred. The reason for lower pre-treatment VAS-values in patients subsequently developing confluent mucositis deserves further studies. Author Disclosure: E. Doerr, None; W. Doerr, None; T. Herrmann, None.
2471
The Predictive Value of Degree of PTV-OAR Overlap on Achieving Parotid Dose Constraints in Head and Neck Simultaneous Integrated Boost-Intensity Modulated Radiation Therapy (SIB-IMRT)
R. Yaparpalvi, K. Mehta, W. Skinner, S. Kalnicki, M. Garg Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY Purpose/Objective(s): The use of IMRT in head and neck cancer has consistently increased in recent years. Reduced xerostomia has been reported and attributed to improved dose distributions achievable with IMRT. RTOG head and neck protocols call for restricting parotid doses to the following–(a) mean dose to either parotid \26 Gy, or (b) at least 50% of the either parotid \30 Gy, or (c) at least 20 cc of the combined volume of both parotid glands will receive \20 Gy. Our purpose is to study relationship between Planning Target Volume-Organ at Risk (PTV-OAR) overlap and the ability to meet Parotid mean dose constraint in SIB-IMRT treatments. Materials/Methods: Parotid gland volume and dose data for 57 head and neck cancer patients treated with SIB–IMRT in our institution were retrospectively analyzed. Patients were prescribed 69.96 Gy to the gross disease (PTVHD) and 54.12 Gy to the subclinical disease (PTVLD) in 33 fractions. Mean PTVHD was 286.6 cc (range 57.4–798.4 cc) and the mean PTVLD was 438.2 cc (range 173.2–759.2 cc). All patients were planned using 6 MV X-rays with 7–9 optimized IMRT beams. Individual Parotid gland and Parotid_PTV overlap volume data was collected along with gland dose-volume information. The mean whole parotid gland volume was 20 cc (range 3.4–42.5 cc). Six patients in this study had combined parotid cumulative volumes of \20 cc. The mean Parotid_PTV overlap was 2.1 cc (range 0–10.3 cc). Parotid gland dose and dosimetric sparing was evaluated as per RTOG Guidelines. All dose calculations were performed using Eclipse planning system (Varian Medical). Results: A total of 114 parotid gland data was analyzed. The results are summarized in Table 1. For Parotid_PTV overlap #15%, a mean Parotid gland dose of #26 Gy was achieved in 46 of 81 glands and in only 3 of 33 glands when Parotid_PTV overlap was .15%. Mean dose #26 Gy was not achieved in remaining 35 Parotid glands even though the PTV overlap was #15%. In these glands, the mean dose was influenced by gland proximity to PTVHD (mean distance 0.8 cm, range 0–4.1 cm) as well as higher PTVHD/PTVLD volume ratio (mean ratio 0.74, range 0.23–1.8, p = 0.003). Parotid gland volume outside the PTV overlap region did not significantly influence the mean gland dose (p = 0.09). In parotid glands with #15% PTV overlap and mean dose #26 Gy, the mean gland distance to the PTVHD was 3.9 cm (range 1.4 cm–8.4 cm, p = 0.002). Conclusions: In head and neck SIB-IMRT, constraining parotid mean dose to #26 Gy is achievable when the Parotid-PTV overlap is \15%. However even with only very small overlap, Parotid gland propinquity to high dose PTVHD region resulted in .26 Gy mean doses.
S463
I. J. Radiation Oncology d Biology d Physics
S464
Volume 69, Number 3, Supplement, 2007
Table 1: Summary of Parotid_PTV Overlap and Parotid Mean dose Parotid_PTV Overlap #15%
$15%
Number of Parotid glands 46 (Mean #26 Gy) Overlap, % Dose, Gy 36 (Mean .26 Gy) Overlap, % Dose, Gy 32 (Mean .26 Gy) Overlap, % Dose, Gy
Mean
Standard Deviation
Standard Error Mean
p Value
5.9 (0–14.7) 21.7 (11.8–27.2)
4.8 3.8
0.7 0.6
p = 0.003
6.8 (0.2–13.2) 31.7 (26.5–50.3)
4.0 5.7
0.7 1.0
p = 0.11
23.9 (15.4–39.6) 39.6 (27.3–56.2)
6.2 8.0
1.2 1.5
p = 0.11
Author Disclosure: R. Yaparpalvi, None; K. Mehta, None; W. Skinner, None; S. Kalnicki, None; M. Garg, None.
2472
Intensity-Modulated Radiation Therapy (IMRT) With Concurrent Taxane-Based Chemotherapy for Locally-Advanced Head and Neck Cancer (LAHNC): Toxicities and Efficacy
R. Diaz1, S. W. Thorpe1, B. A. Murphy1, W. Kirby1, B. B. Burkey1, C. H. Chung2, B. Shakhtour1, P. Murphy3, M. Beach4, A. J. Cmelak1 1 Vanderbilt University Medical Center, Nashville, TN, 2Nashville Veterans Hospital, Nashville, TN, 3Sarah Cannon Cancer Center, Nashville, TN, 4Williamson County Medical Center, Franklin, TN
Purpose/Objective(s): The addition of chemotherapy to radiotherapy improves survival in LAHNC at the expense of higher toxicity. IMRT for LAHNC provides a means to minimize dose to normal tissue. Our experience with concurrent IMRT and taxanebased chemotherapy in 128 sequential LAHNC patients is presented. Materials/Methods: From December 2002 to October 2006, 128 patients with LAHNC were treated with IMRT and concurrent taxane-based chemotherapy for curative intent. Sites included hypopharynx-5; larynx-27; nasopharynx-10; oral cavity-6; oropharynx-75; sinus-2; unknown primary-3. AJCC stages II-3; III-35; IVA-73; and IVB-17. In order to simplify IMRT planning, a single differential IMRT fractionation regimen was developed: 2.1 Gy/day to gross disease with ±5% homogeneity (69.3 Gy in 33 fractions), and 1.7 Gy to prophylactic nodal sites down to the clavicles (56.1 Gy, homogeneity +8% to 5%). 50% of the volume of sensitive tissue (oral cavity, parotids, back of neck, larynx/trachea, and esophagus) was limited to #25 Gy. Weekly paclitaxel 30 mg/m2 and carboplatin AUC 1 were given concurrently with IMRT to all 128 patients. The majority of patients with N2 or N3 disease (78%) also received weekly induction chemotherapy with paclitaxel 60 mg/m2 and carboplatin AUC 2. Chemotherapy was held for ANC \1000, platelets \100 k, or grade 4 mucositis. PEG was placed for $10% weight loss. Results: This regimen is highly feasible. One patient died 3 days after treatment of unknown cause. One patient discontinued treatment early due to grade 2 mucositis and dysphagia. Five patients required a treatment break from radiation greater than 1 week. Mean percent weight loss was 7%. PEGs were placed before beginning treatment in 5% and additional 66% required PEG during treatment; 8% required PEG use .1 year. Grade 3 mucositis occurred in 70% (1% Grade 4) and grade 3 dermatitis was seen in 64% (4% grade 4). Eleven patients (9%) developed osteoradionecrosis. 70% of patients developed hypothyroidism after their treatment. There were no patients with nadir sepsis nor significant nephropathy or GI toxicity. Late xerostomia is #grade 1 in all patients. Mean follow-up is 20.7 months. One and two year survival was 87% and 79%, respectively. There was no statistical difference between overall survival and disease site. Local control was 95% at 1 year and 91% at 2 years. Regional control is 96% at 1 year and 95% at 2 years. One and two year relapse free survival (RFS) was 77% and 64%, respectively. Distant metastasis developed in 9%. Percent weight loss during IMRT correlated with RFS (p \ 0.02) and with survival (p \ 0.1). Conclusions: Differential-dose IMRT with paclitaxel and carboplatin is extremely feasible with excellent dose delivery of both radiation and chemotherapy. Minimizing dose (#25 Gy) to sensitive tissues and strict use of IMRT homogeneity criteria appear to prevent significant long-term swallowing difficulties. Early toxicities are low with impressive tumor control. Development of hypothyroidism, however, appears higher with IMRT than historical rates using 3-D conformal radiation. Author Disclosure: R. Diaz, None; S.W. Thorpe, None; B.A. Murphy, None; W. Kirby, None; B.B. Burkey, None; C.H. Chung, None; B. Shakhtour, None; P. Murphy, None; M. Beach, None; A.J. Cmelak, None.
2473
Dosimetric Evaluation of the Brachial Plexus in the Treatment of Head and Neck Cancer
J. E. McGary1, W. H. Grant1, B. S. Teh1, A. C. Paulino1, E. Butler2 1 Department of Radiation Oncology, Baylor College of Medicine, Houston, TX, 2Department of Radiation Oncology, The Methodist Hospital, Houston, TX
Purpose/Objective(s): To evaluate the dose to the brachial plexus in patients treated with head and neck cancer by various treatment techniques, and to evaluate how placing a limitation of 60 Gy on the brachial plexus affects coverage of the target. Materials/Methods: The brachial plexus is not routinely delineated as an avoidance structure in the treatment of head and neck malignancies. The medial vertical extent of the roots was from the C4-5 interspace to T1-2 interspace. It continued inferiorly, above the subclavian artery, between the anterior and middle scalene muscles to traverse the interscalene triangle and then the costoclavicular space (between the inferior surface of the clavicle and the upper surface of the first rib). It then continues to reach the space between the pectoralis minor muscle and the anterosuperior chest wall where it finally surrounds the axillary artery, lateral to the pectoralis minor muscle. The anatomical location of the brachial plexus was defined utilizing the Anatom-e target delineation system. A patient with a T1N3 (7 cm right sided lymph node) undifferentiated carcinoma of the nasopharynx and a patient with T3N2b squamous cell carcinoma of the larynx status post total laryngectomy and left radical neck dissection were chosen as patient examples. The following dosimetric parameters for the brachial plexus were evaluated on treatment plans: mean dose, maximum
2470
Self-Assessment of Oral Mucositis by Patients During Radio(chemo)therapy for Head and Neck Tumors Using a Visual Analogue Scale
E. Doerr, W. Doerr, T. Herrmann University of Technology Dresden, Dresden, Germany Purpose/Objective(s): Oral Mucositis is a frequent and severe early side effect during radio(chemo)therapy for advanced headand-neck cancer, which often necessitates interruption of the treatment. In the present investigation, self-assessment of the oral cavity by the patients using a visual analogue scale (VAS) was compared to mucositis scores according to the RTOG/EORTC classification system. Materials/Methods: A total of 366 patients with head-and-neck tumours receiving a dose $40 Gy to the oral mucosa were included in the analysis, who were part of a mouth care study comparing dexpanthenol vs. water mouth washes. In the latter investigation, no differences between the study arms and hence, the data could be pooled. Treatment protocols comprised conventional fractionation, hyperfractionation and a combination of both radiochemotherapy. Informed consent was provided by all patients. Professional mouth care including intensive mouth washes with water was performed once daily. In addition to these obligatory procedures, repeated mouth washes with sage tea were recommended. Scoring of mucositis by the investigators according to the RTOG/EORTC-system was done daily. For weekly self-assessment of the oral cavity by the patients, a visual analogue scale (VAS) was applied, in which the patient marks the evaluation of the oral cavity between ‘‘very poor’’ and ‘‘excellent’’. Quantitation is performed according to the location of the patient’s mark as a number between 0 and 10. Results: VAS analysis at the onset of the treatment yielded a significantly lower value of 7.3 ± 0.1 for those patients who subsequently developed mucositis grade 3, compared to 8.2 ± 0.2 for patients without subsequent confluent mucositis. During the treatment, VAS-values significantly decreased; the initial difference between both groups remained nearly constant. From the third treatment week, the subjective VAS-values were significantly lower in those patients that were scored with confluent oral mucositis. Conclusions: Objective scoring according to RTOG/EORTC clearly mirrores the subjective assessment of the patients; the agreement indicates that mucositis significantly impacts on the patients’ quality of life. The value of professional mouth care is un-questioned, as all patients were compliant and no mucositis-associated treatment interruptions occurred. The reason for lower pre-treatment VAS-values in patients subsequently developing confluent mucositis deserves further studies. Author Disclosure: E. Doerr, None; W. Doerr, None; T. Herrmann, None.
2471
The Predictive Value of Degree of PTV-OAR Overlap on Achieving Parotid Dose Constraints in Head and Neck Simultaneous Integrated Boost-Intensity Modulated Radiation Therapy (SIB-IMRT)
R. Yaparpalvi, K. Mehta, W. Skinner, S. Kalnicki, M. Garg Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY Purpose/Objective(s): The use of IMRT in head and neck cancer has consistently increased in recent years. Reduced xerostomia has been reported and attributed to improved dose distributions achievable with IMRT. RTOG head and neck protocols call for restricting parotid doses to the following–(a) mean dose to either parotid \26 Gy, or (b) at least 50% of the either parotid \30 Gy, or (c) at least 20 cc of the combined volume of both parotid glands will receive \20 Gy. Our purpose is to study relationship between Planning Target Volume-Organ at Risk (PTV-OAR) overlap and the ability to meet Parotid mean dose constraint in SIB-IMRT treatments. Materials/Methods: Parotid gland volume and dose data for 57 head and neck cancer patients treated with SIB–IMRT in our institution were retrospectively analyzed. Patients were prescribed 69.96 Gy to the gross disease (PTVHD) and 54.12 Gy to the subclinical disease (PTVLD) in 33 fractions. Mean PTVHD was 286.6 cc (range 57.4–798.4 cc) and the mean PTVLD was 438.2 cc (range 173.2–759.2 cc). All patients were planned using 6 MV X-rays with 7–9 optimized IMRT beams. Individual Parotid gland and Parotid_PTV overlap volume data was collected along with gland dose-volume information. The mean whole parotid gland volume was 20 cc (range 3.4–42.5 cc). Six patients in this study had combined parotid cumulative volumes of \20 cc. The mean Parotid_PTV overlap was 2.1 cc (range 0–10.3 cc). Parotid gland dose and dosimetric sparing was evaluated as per RTOG Guidelines. All dose calculations were performed using Eclipse planning system (Varian Medical). Results: A total of 114 parotid gland data was analyzed. The results are summarized in Table 1. For Parotid_PTV overlap #15%, a mean Parotid gland dose of #26 Gy was achieved in 46 of 81 glands and in only 3 of 33 glands when Parotid_PTV overlap was .15%. Mean dose #26 Gy was not achieved in remaining 35 Parotid glands even though the PTV overlap was #15%. In these glands, the mean dose was influenced by gland proximity to PTVHD (mean distance 0.8 cm, range 0–4.1 cm) as well as higher PTVHD/PTVLD volume ratio (mean ratio 0.74, range 0.23–1.8, p = 0.003). Parotid gland volume outside the PTV overlap region did not significantly influence the mean gland dose (p = 0.09). In parotid glands with #15% PTV overlap and mean dose #26 Gy, the mean gland distance to the PTVHD was 3.9 cm (range 1.4 cm–8.4 cm, p = 0.002). Conclusions: In head and neck SIB-IMRT, constraining parotid mean dose to #26 Gy is achievable when the Parotid-PTV overlap is \15%. However even with only very small overlap, Parotid gland propinquity to high dose PTVHD region resulted in .26 Gy mean doses.
S463
I. J. Radiation Oncology d Biology d Physics
S464
Volume 69, Number 3, Supplement, 2007
Table 1: Summary of Parotid_PTV Overlap and Parotid Mean dose Parotid_PTV Overlap #15%
$15%
Number of Parotid glands 46 (Mean #26 Gy) Overlap, % Dose, Gy 36 (Mean .26 Gy) Overlap, % Dose, Gy 32 (Mean .26 Gy) Overlap, % Dose, Gy
Mean
Standard Deviation
Standard Error Mean
p Value
5.9 (0–14.7) 21.7 (11.8–27.2)
4.8 3.8
0.7 0.6
p = 0.003
6.8 (0.2–13.2) 31.7 (26.5–50.3)
4.0 5.7
0.7 1.0
p = 0.11
23.9 (15.4–39.6) 39.6 (27.3–56.2)
6.2 8.0
1.2 1.5
p = 0.11
Author Disclosure: R. Yaparpalvi, None; K. Mehta, None; W. Skinner, None; S. Kalnicki, None; M. Garg, None.
2472
Intensity-Modulated Radiation Therapy (IMRT) With Concurrent Taxane-Based Chemotherapy for Locally-Advanced Head and Neck Cancer (LAHNC): Toxicities and Efficacy
R. Diaz1, S. W. Thorpe1, B. A. Murphy1, W. Kirby1, B. B. Burkey1, C. H. Chung2, B. Shakhtour1, P. Murphy3, M. Beach4, A. J. Cmelak1 1 Vanderbilt University Medical Center, Nashville, TN, 2Nashville Veterans Hospital, Nashville, TN, 3Sarah Cannon Cancer Center, Nashville, TN, 4Williamson County Medical Center, Franklin, TN
Purpose/Objective(s): The addition of chemotherapy to radiotherapy improves survival in LAHNC at the expense of higher toxicity. IMRT for LAHNC provides a means to minimize dose to normal tissue. Our experience with concurrent IMRT and taxanebased chemotherapy in 128 sequential LAHNC patients is presented. Materials/Methods: From December 2002 to October 2006, 128 patients with LAHNC were treated with IMRT and concurrent taxane-based chemotherapy for curative intent. Sites included hypopharynx-5; larynx-27; nasopharynx-10; oral cavity-6; oropharynx-75; sinus-2; unknown primary-3. AJCC stages II-3; III-35; IVA-73; and IVB-17. In order to simplify IMRT planning, a single differential IMRT fractionation regimen was developed: 2.1 Gy/day to gross disease with ±5% homogeneity (69.3 Gy in 33 fractions), and 1.7 Gy to prophylactic nodal sites down to the clavicles (56.1 Gy, homogeneity +8% to 5%). 50% of the volume of sensitive tissue (oral cavity, parotids, back of neck, larynx/trachea, and esophagus) was limited to #25 Gy. Weekly paclitaxel 30 mg/m2 and carboplatin AUC 1 were given concurrently with IMRT to all 128 patients. The majority of patients with N2 or N3 disease (78%) also received weekly induction chemotherapy with paclitaxel 60 mg/m2 and carboplatin AUC 2. Chemotherapy was held for ANC \1000, platelets \100 k, or grade 4 mucositis. PEG was placed for $10% weight loss. Results: This regimen is highly feasible. One patient died 3 days after treatment of unknown cause. One patient discontinued treatment early due to grade 2 mucositis and dysphagia. Five patients required a treatment break from radiation greater than 1 week. Mean percent weight loss was 7%. PEGs were placed before beginning treatment in 5% and additional 66% required PEG during treatment; 8% required PEG use .1 year. Grade 3 mucositis occurred in 70% (1% Grade 4) and grade 3 dermatitis was seen in 64% (4% grade 4). Eleven patients (9%) developed osteoradionecrosis. 70% of patients developed hypothyroidism after their treatment. There were no patients with nadir sepsis nor significant nephropathy or GI toxicity. Late xerostomia is #grade 1 in all patients. Mean follow-up is 20.7 months. One and two year survival was 87% and 79%, respectively. There was no statistical difference between overall survival and disease site. Local control was 95% at 1 year and 91% at 2 years. Regional control is 96% at 1 year and 95% at 2 years. One and two year relapse free survival (RFS) was 77% and 64%, respectively. Distant metastasis developed in 9%. Percent weight loss during IMRT correlated with RFS (p \ 0.02) and with survival (p \ 0.1). Conclusions: Differential-dose IMRT with paclitaxel and carboplatin is extremely feasible with excellent dose delivery of both radiation and chemotherapy. Minimizing dose (#25 Gy) to sensitive tissues and strict use of IMRT homogeneity criteria appear to prevent significant long-term swallowing difficulties. Early toxicities are low with impressive tumor control. Development of hypothyroidism, however, appears higher with IMRT than historical rates using 3-D conformal radiation. Author Disclosure: R. Diaz, None; S.W. Thorpe, None; B.A. Murphy, None; W. Kirby, None; B.B. Burkey, None; C.H. Chung, None; B. Shakhtour, None; P. Murphy, None; M. Beach, None; A.J. Cmelak, None.
2473
Dosimetric Evaluation of the Brachial Plexus in the Treatment of Head and Neck Cancer
J. E. McGary1, W. H. Grant1, B. S. Teh1, A. C. Paulino1, E. Butler2 1 Department of Radiation Oncology, Baylor College of Medicine, Houston, TX, 2Department of Radiation Oncology, The Methodist Hospital, Houston, TX
Purpose/Objective(s): To evaluate the dose to the brachial plexus in patients treated with head and neck cancer by various treatment techniques, and to evaluate how placing a limitation of 60 Gy on the brachial plexus affects coverage of the target. Materials/Methods: The brachial plexus is not routinely delineated as an avoidance structure in the treatment of head and neck malignancies. The medial vertical extent of the roots was from the C4-5 interspace to T1-2 interspace. It continued inferiorly, above the subclavian artery, between the anterior and middle scalene muscles to traverse the interscalene triangle and then the costoclavicular space (between the inferior surface of the clavicle and the upper surface of the first rib). It then continues to reach the space between the pectoralis minor muscle and the anterosuperior chest wall where it finally surrounds the axillary artery, lateral to the pectoralis minor muscle. The anatomical location of the brachial plexus was defined utilizing the Anatom-e target delineation system. A patient with a T1N3 (7 cm right sided lymph node) undifferentiated carcinoma of the nasopharynx and a patient with T3N2b squamous cell carcinoma of the larynx status post total laryngectomy and left radical neck dissection were chosen as patient examples. The following dosimetric parameters for the brachial plexus were evaluated on treatment plans: mean dose, maximum