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Optimal field arrangement for elective irradiation of neck nodes in conformal radiotherapy of pharyngeal tumours
Proceedings of the 46th Annual ASTRO Meeting
The radiotherapy protocol changed over time at our institution. Before 1994, the treatment A consisted of two fractions per day (2x 2.1 Gy), preceded by a dose of 50 mg/m2 carboplatinum i.v. daily. A total radiation dose of 56.70 Gy was applied to the neck and the primary tumour over 6 weeks as a split course regimen with a brake of 2 weeks. After 1994, treatment B consisted of a conventional radiotherapy (50 Gy ⫹ 10 Gy Boost) delivered in 30 treatment fractions of 2.0 Gy. Follow-up: All patients were examined every 6 months during the first 3 years after therapy, and every year after this period. They underwent clinical ENT-examination including magnifying laryngososcopy, ultrasound, and/or a computed tomography of the head and neck region if indicated. Statistics: Survival and local-regional control probabilities were calculated from the day of surgery. Disease Free Survival (DFS) was defined as the absence of recurrent disease above the clavicles and the absence of distant metastases. The Kaplan-Meier product-limit method was used to determine survival and the time to local failure. The log rank method was used to test for statistical significance. Multivariate analyses were estimated by means of the Cox proportional hazards model. Follow-up data were available on all patients. Each of them was followed until death for those who died or until December 2001 for those who were alive. The median follow-up period was 75 months (range 31 to 137 months). The Disease Specific Survival (DSS) and the Locoregional Control (LRC) were estimated with the Kaplan Meier curves. Results: Patients had 5-year locoregional control (LRC) and diseases specific survival (DSS) rates of 62.5 %, and 45 %, respectively. The 5-year DSS was 66 % and 38 % for the stage III and IV, respectively (p ⫽ 0.006). Patients treated with a hemoglobin level superior or equal to 13.5 g/dl before radiotherapy had a 5-year DSS of 48.5% as compared with 37 % for patients treated with a hemoglobin level inferior to 13.5 g/dl (p ⫽ 0.01). The largest difference was found between the patients who received treatment B and who had a hemoglobin level superior or equal to 13.5 g/dl before radiotherapy and the patients who received treatment A who had a hemoglobin level inferior to 13.5 g/dl. In the first group the 5-year DSS was 54% compared with 38% in the second group (p ⫽ 0.002). Conclusions: In this series of patients with advanced head and neck tumours transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Laser surgery apparently leaves patients in a better clinical condition with higher hemoglobin levels and reduced surgical trauma, which is both likely enhancing the efficacy of postoperative radiotherapy.
2299
Favorable Outcome of Combined Proton Radiotherapy and Chemotherapy for T4 Nasopharyngeal Carcinoma
N. J. Liebsch,1,3 D. G. Deschler,2,3 J. F. McIntyre,1,3 J. A. Adams,1,3 R. J. Frankenthaler,2,3 R. L. Fabian,2,3 A. W. Chan1,3 Radiation Oncology, Massachusetts General Hospital, Boston, MA, 2Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, 3Harvard Medical School, Boston, MA
1
Purpose/Objective: To evaluate the toxicity and outcome of proton radiotherapy with and without chemotherapy in the treatment of T4 nasopharyngeal carcinoma. Materials/Methods: Between 1990 and 2002, 17 patients with newly diagnosed T4 N0-3 nasopharyngeal carcinoma received combined conformal proton and photon radiotherapy. Seventy-one percentage of patients had World Health Organization type 2-3 histology The median prescribed dose to the gross target volume was 73.6 Cobalt-Gray-Equivalent (CGE) (range 69-76.8). Eleven patients received accelerated hyperfractionated radiotherapy. Ten patients received induction or concurrent chemotherapy: 3 with induction docetaxel, cisplatin, and 5FU; and 7 with concurrent cisplatin, carboplatin, or taxol. Results: All patients except one completed the planned concurrent radiation and chemotherapy treatments. With a median follow-up of 43 months, 1 and 2 patients developed local and systemic failures, respectively. There was no neck recurrence. The locoregional control and relapse-free survival rates at 3 years were 92% and 79%, respectively. For patients who received chemotherapy, the 3-year relapse-free survival rate was 91% compared to 50% for those without chemotherapy (p ⫽ 0.09). The overall 3-year overall survival rate was 74%. For patients who received chemotherapy, the 3-year overall survival rate was 91% compared to 40% for those without chemotherapy (p ⫽ 0.01). Late toxicities included five patients with radiographic changes of the temporal lobes and one osteoradionecrosis of the mandible. Conclusions: This retrospective analysis suggests that combined use of chemotherapy with proton radiotherapy results in improved disease-free and overall survivals in patients with T4 nasopharyngeal carcinoma. The use of this treatment strategy will be further investigated in a Phase II trial at our Northeast Proton Therapy Center. This study is supported in part by the National Institute of Health, NCI-PO1-CA21239.
2300
Optimal Field Arrangement for Elective Irradiation of Neck Nodes in Conformal Radiotherapy of Pharyngeal Tumours
C. Usher,1 S. Patel,1 A. K. Elhamri,1 A. Taylor,2 M.E. Powell2 Radiotherapy Physics, St. Bartholomew’s Hospital, London, United Kingdom, 2Radiotherapy and Clinical Oncology, St Bartholomew’s Hospital, London, United Kingdom
1
Purpose/Objective: The majority of patients with pharyngeal tumours have prophylactic irradiation of the lymph nodes in the neck. Conventional planning consists of two lateral fields to treat the primary tumour and upper neck nodes and the lower neck nodes are treated with a single matched direct anterior field. Routine CT planning for all ENT patients was initially introduced at St Bartholomews Hospital to facilitate the planning of a single isocentre, asymmetric match technique. All fields were defined conventionally using simulator radiographs. The availability of the dose distribution for the whole of the treated volume raised the question of the adequacy of this field arrangement to cover the PTV in the lower neck region. Examination of the dose distribution in the region below the match line led to an increasing number of requests from clinical oncologists to add a posterior neck field to increase the depth of the 95% isodose. This study was undertaken to make a quantitative assessment of the dosimetry of the lower neck nodes and to determine whether there is dosimetric justification for increasing the complexity of planning and treatment.
S515
S516
I. J. Radiation Oncology
● Biology ● Physics
Volume 60, Number 1, Supplement, 2004
Materials/Methods: Using the RTOG Consensus guidelines, lymph node regions I-V were drawn on the planning CT scans of 10 patients. Every nodal group was treated as a separate PTV for treatment planning. Two plans were produced for each patient on Cadplan (Varian, Palo Alto, US). In one plan, anterior and posterior lower neck fields were weighted to give the prescribed dose to the neck reference point (2cm depth, 3cm lateral to midline) and to ensure the 95% isodose PTV coverage was optimised. The other plan used a single anterior field normalised to the same reference point. Both plans had identical fields above the match line. DVHs for the PTV regions below the match line were examined for the 20 plans. They were compared to assess the difference in coverage of the nodes between the two techniques. The mean doses were compared, as was the volume receiving less than 90% and 95% of the prescribed dose. Results: The mean volume of the combined nodal PTV covered by the 95% isodose was 91% for plans with an anterior field only and 93% for plans with anterior and posterior fields. The mean volume of PTV covered by the 90% isodose was 91% for plans with an anterior field only and 95% for plans with anterior and posterior fields. Regions of particular underdosage were in the build up region and the posterior nodes. Using an anterior field only, a mean of 12% of the level 5 nodal PTV received less than 95% of the prescribed dose. This reduced to 4% when a posterior field was added. Conclusions: The conventional field arrangement using a single anterior field to treat the lower neck nodes inadequately treats target volumes which include posterior nodes, particularly the level 5 nodes. The addition of a posterior field significantly improves coverage of the PTV and has now become standard in our centre. This field arrangement should be considered for any studies which compare conventional radiotherapy with intensity modulated radiotherapy.
2301
Posttreatment Plasma TGF-beta 1 Level Predicts Late Morbidity in Advanced Head and Neck Cancer
1
D. Feltl, E. Zavadova,2 M. Pala,3 P. Hozak4 Department of Radiotherapy and Oncology, University Hospital Kralovske Vinohrady, Prague, Czech Republic, 2St. Elisabeth Hospital, Prague, Czech Republic, 3Institute of Radiation Oncology, Prague, Czech Republic, 4Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic 1
Purpose/Objective: Predictive factors for treatment response and morbidity are of huge interest in radiation oncology. If powerful enough, they enable us to individualize the treatment, e.g. escalate the dose of radiotherapy. We tested the predictive power of TGF-beta 1 in advanced head and neck cancer. Materials/Methods: Between 2001–2002, 36 patients with advanced inoperable squamous head and neck cancer treated with radiotherapy with or without simultaneous chemotherapy were evaluated for their plasma TGF-beta 1 levels prior to the treatment, in the middle of the radiotherapy course and at the end of the treatment. The patients were assessed for treatment response and late morbidity. Predictive value of TGF-beta 1 level on either of the assessed parameters was tested using Mann-Whitney test. Results: There were 29 eligible patients (pts), the rest being lost of follow-up. Of these 29 pts, 18 achieved complete response, 8 partial response and three pts progressed primarily. After a median follow-up of 16 months (range 3–28), we recorded 16 cases of grade ⬎1 late morbidity. We found that post treatment elevated plasma TGF-beta 1 level predicts late morbidity grade ⬎1 (p ⫽ 0,05, see graph) rather than pretreatment level (p ⫽ 0,062). Plasma TGF-beta 1 level has no predictive value to the treatment response neither pretreatment nor post treatment (CR vs. no CR, p ⫽ 0,125 and 0,252, respectively). Conclusions: Post treatment plasma TGF-beta 1 level can predict late morbidity grade ⬎1 in advanced head and neck cancer treated with radio(chemo)therapy. This could make a basis for dose escalation in selected patients, an approach known as “TGF-beta 1 directed radiotherapy”.
2302
Dosimetric Uncertainties in Matched IMRT and Conventional Fields for Head and Neck Cancer Radiotherapy
J. L. Rembert,1 P. Xia,1 M.K. Bucci,1 C. Akazawa,1 J.M. Quivey1 Radiation Oncology, University of California, San Francisco, San Francisco, CA
1
Purpose/Objective: Three techniques using IMRT for the treatment of primary head and neck tumors and nodal levels I-V are commonly employed: (A) extended-field IMRT with a single isocenter to treat the entire target volume; (B) a three field method
The radiotherapy protocol changed over time at our institution. Before 1994, the treatment A consisted of two fractions per day (2x 2.1 Gy), preceded by a dose of 50 mg/m2 carboplatinum i.v. daily. A total radiation dose of 56.70 Gy was applied to the neck and the primary tumour over 6 weeks as a split course regimen with a brake of 2 weeks. After 1994, treatment B consisted of a conventional radiotherapy (50 Gy ⫹ 10 Gy Boost) delivered in 30 treatment fractions of 2.0 Gy. Follow-up: All patients were examined every 6 months during the first 3 years after therapy, and every year after this period. They underwent clinical ENT-examination including magnifying laryngososcopy, ultrasound, and/or a computed tomography of the head and neck region if indicated. Statistics: Survival and local-regional control probabilities were calculated from the day of surgery. Disease Free Survival (DFS) was defined as the absence of recurrent disease above the clavicles and the absence of distant metastases. The Kaplan-Meier product-limit method was used to determine survival and the time to local failure. The log rank method was used to test for statistical significance. Multivariate analyses were estimated by means of the Cox proportional hazards model. Follow-up data were available on all patients. Each of them was followed until death for those who died or until December 2001 for those who were alive. The median follow-up period was 75 months (range 31 to 137 months). The Disease Specific Survival (DSS) and the Locoregional Control (LRC) were estimated with the Kaplan Meier curves. Results: Patients had 5-year locoregional control (LRC) and diseases specific survival (DSS) rates of 62.5 %, and 45 %, respectively. The 5-year DSS was 66 % and 38 % for the stage III and IV, respectively (p ⫽ 0.006). Patients treated with a hemoglobin level superior or equal to 13.5 g/dl before radiotherapy had a 5-year DSS of 48.5% as compared with 37 % for patients treated with a hemoglobin level inferior to 13.5 g/dl (p ⫽ 0.01). The largest difference was found between the patients who received treatment B and who had a hemoglobin level superior or equal to 13.5 g/dl before radiotherapy and the patients who received treatment A who had a hemoglobin level inferior to 13.5 g/dl. In the first group the 5-year DSS was 54% compared with 38% in the second group (p ⫽ 0.002). Conclusions: In this series of patients with advanced head and neck tumours transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Laser surgery apparently leaves patients in a better clinical condition with higher hemoglobin levels and reduced surgical trauma, which is both likely enhancing the efficacy of postoperative radiotherapy.
2299
Favorable Outcome of Combined Proton Radiotherapy and Chemotherapy for T4 Nasopharyngeal Carcinoma
N. J. Liebsch,1,3 D. G. Deschler,2,3 J. F. McIntyre,1,3 J. A. Adams,1,3 R. J. Frankenthaler,2,3 R. L. Fabian,2,3 A. W. Chan1,3 Radiation Oncology, Massachusetts General Hospital, Boston, MA, 2Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, 3Harvard Medical School, Boston, MA
1
Purpose/Objective: To evaluate the toxicity and outcome of proton radiotherapy with and without chemotherapy in the treatment of T4 nasopharyngeal carcinoma. Materials/Methods: Between 1990 and 2002, 17 patients with newly diagnosed T4 N0-3 nasopharyngeal carcinoma received combined conformal proton and photon radiotherapy. Seventy-one percentage of patients had World Health Organization type 2-3 histology The median prescribed dose to the gross target volume was 73.6 Cobalt-Gray-Equivalent (CGE) (range 69-76.8). Eleven patients received accelerated hyperfractionated radiotherapy. Ten patients received induction or concurrent chemotherapy: 3 with induction docetaxel, cisplatin, and 5FU; and 7 with concurrent cisplatin, carboplatin, or taxol. Results: All patients except one completed the planned concurrent radiation and chemotherapy treatments. With a median follow-up of 43 months, 1 and 2 patients developed local and systemic failures, respectively. There was no neck recurrence. The locoregional control and relapse-free survival rates at 3 years were 92% and 79%, respectively. For patients who received chemotherapy, the 3-year relapse-free survival rate was 91% compared to 50% for those without chemotherapy (p ⫽ 0.09). The overall 3-year overall survival rate was 74%. For patients who received chemotherapy, the 3-year overall survival rate was 91% compared to 40% for those without chemotherapy (p ⫽ 0.01). Late toxicities included five patients with radiographic changes of the temporal lobes and one osteoradionecrosis of the mandible. Conclusions: This retrospective analysis suggests that combined use of chemotherapy with proton radiotherapy results in improved disease-free and overall survivals in patients with T4 nasopharyngeal carcinoma. The use of this treatment strategy will be further investigated in a Phase II trial at our Northeast Proton Therapy Center. This study is supported in part by the National Institute of Health, NCI-PO1-CA21239.
2300
Optimal Field Arrangement for Elective Irradiation of Neck Nodes in Conformal Radiotherapy of Pharyngeal Tumours
C. Usher,1 S. Patel,1 A. K. Elhamri,1 A. Taylor,2 M.E. Powell2 Radiotherapy Physics, St. Bartholomew’s Hospital, London, United Kingdom, 2Radiotherapy and Clinical Oncology, St Bartholomew’s Hospital, London, United Kingdom
1
Purpose/Objective: The majority of patients with pharyngeal tumours have prophylactic irradiation of the lymph nodes in the neck. Conventional planning consists of two lateral fields to treat the primary tumour and upper neck nodes and the lower neck nodes are treated with a single matched direct anterior field. Routine CT planning for all ENT patients was initially introduced at St Bartholomews Hospital to facilitate the planning of a single isocentre, asymmetric match technique. All fields were defined conventionally using simulator radiographs. The availability of the dose distribution for the whole of the treated volume raised the question of the adequacy of this field arrangement to cover the PTV in the lower neck region. Examination of the dose distribution in the region below the match line led to an increasing number of requests from clinical oncologists to add a posterior neck field to increase the depth of the 95% isodose. This study was undertaken to make a quantitative assessment of the dosimetry of the lower neck nodes and to determine whether there is dosimetric justification for increasing the complexity of planning and treatment.
S515
S516
I. J. Radiation Oncology
● Biology ● Physics
Volume 60, Number 1, Supplement, 2004
Materials/Methods: Using the RTOG Consensus guidelines, lymph node regions I-V were drawn on the planning CT scans of 10 patients. Every nodal group was treated as a separate PTV for treatment planning. Two plans were produced for each patient on Cadplan (Varian, Palo Alto, US). In one plan, anterior and posterior lower neck fields were weighted to give the prescribed dose to the neck reference point (2cm depth, 3cm lateral to midline) and to ensure the 95% isodose PTV coverage was optimised. The other plan used a single anterior field normalised to the same reference point. Both plans had identical fields above the match line. DVHs for the PTV regions below the match line were examined for the 20 plans. They were compared to assess the difference in coverage of the nodes between the two techniques. The mean doses were compared, as was the volume receiving less than 90% and 95% of the prescribed dose. Results: The mean volume of the combined nodal PTV covered by the 95% isodose was 91% for plans with an anterior field only and 93% for plans with anterior and posterior fields. The mean volume of PTV covered by the 90% isodose was 91% for plans with an anterior field only and 95% for plans with anterior and posterior fields. Regions of particular underdosage were in the build up region and the posterior nodes. Using an anterior field only, a mean of 12% of the level 5 nodal PTV received less than 95% of the prescribed dose. This reduced to 4% when a posterior field was added. Conclusions: The conventional field arrangement using a single anterior field to treat the lower neck nodes inadequately treats target volumes which include posterior nodes, particularly the level 5 nodes. The addition of a posterior field significantly improves coverage of the PTV and has now become standard in our centre. This field arrangement should be considered for any studies which compare conventional radiotherapy with intensity modulated radiotherapy.
2301
Posttreatment Plasma TGF-beta 1 Level Predicts Late Morbidity in Advanced Head and Neck Cancer
1
D. Feltl, E. Zavadova,2 M. Pala,3 P. Hozak4 Department of Radiotherapy and Oncology, University Hospital Kralovske Vinohrady, Prague, Czech Republic, 2St. Elisabeth Hospital, Prague, Czech Republic, 3Institute of Radiation Oncology, Prague, Czech Republic, 4Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic 1
Purpose/Objective: Predictive factors for treatment response and morbidity are of huge interest in radiation oncology. If powerful enough, they enable us to individualize the treatment, e.g. escalate the dose of radiotherapy. We tested the predictive power of TGF-beta 1 in advanced head and neck cancer. Materials/Methods: Between 2001–2002, 36 patients with advanced inoperable squamous head and neck cancer treated with radiotherapy with or without simultaneous chemotherapy were evaluated for their plasma TGF-beta 1 levels prior to the treatment, in the middle of the radiotherapy course and at the end of the treatment. The patients were assessed for treatment response and late morbidity. Predictive value of TGF-beta 1 level on either of the assessed parameters was tested using Mann-Whitney test. Results: There were 29 eligible patients (pts), the rest being lost of follow-up. Of these 29 pts, 18 achieved complete response, 8 partial response and three pts progressed primarily. After a median follow-up of 16 months (range 3–28), we recorded 16 cases of grade ⬎1 late morbidity. We found that post treatment elevated plasma TGF-beta 1 level predicts late morbidity grade ⬎1 (p ⫽ 0,05, see graph) rather than pretreatment level (p ⫽ 0,062). Plasma TGF-beta 1 level has no predictive value to the treatment response neither pretreatment nor post treatment (CR vs. no CR, p ⫽ 0,125 and 0,252, respectively). Conclusions: Post treatment plasma TGF-beta 1 level can predict late morbidity grade ⬎1 in advanced head and neck cancer treated with radio(chemo)therapy. This could make a basis for dose escalation in selected patients, an approach known as “TGF-beta 1 directed radiotherapy”.
2302
Dosimetric Uncertainties in Matched IMRT and Conventional Fields for Head and Neck Cancer Radiotherapy
J. L. Rembert,1 P. Xia,1 M.K. Bucci,1 C. Akazawa,1 J.M. Quivey1 Radiation Oncology, University of California, San Francisco, San Francisco, CA
1
Purpose/Objective: Three techniques using IMRT for the treatment of primary head and neck tumors and nodal levels I-V are commonly employed: (A) extended-field IMRT with a single isocenter to treat the entire target volume; (B) a three field method