Radiation Oncology
BioMed Central
Open Access
Research
Intensity modulated radiotherapy (IMRT) in patients with carcinomas of the paranasal sinuses: clinical benefit for complex shaped target volumes Stephanie E Combs*1,2, Stephan Konkel1,2, Daniela Schulz-Ertner1,2, Marc W Münter1,2, Jürgen Debus1,2, Peter E Huber†1,2 and Christoph Thilmann†1,2 Address: 1University of Heidelberg, Department of Radiation Oncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany and 2German Cancer Center (dkfz), Clinical Cooperation Unit Radiation Oncology, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany Email: Stephanie E Combs* -
[email protected]; Stephan Konkel -
[email protected]; Daniela SchulzErtner -
[email protected]; Marc W Münter -
[email protected]; Jürgen Debus -
[email protected]; Peter E Huber -
[email protected]; Christoph Thilmann -
[email protected] * Corresponding author †Equal contributors
Published: 21 July 2006 Radiation Oncology 2006, 1:23
doi:10.1186/1748-717X-1-23
Received: 12 June 2006 Accepted: 21 July 2006
This article is available from: http://www.ro-journal.com/content/1/1/23 © 2006 Combs et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Introduction: The aim of the study was to evaluate the clinical outcome of intensity modulated radiotherapy (IMRT) in 46 patients with paranasal sinus tumors with special respect to treatment-related toxicity. Patients and methods: We treated 46 patients with histologically proven tumors of the paranasal sinuses with IMRT. Histological classification included squamous cell carcinoma in 6, adenocarcinoma in 8, adenoidcystic carcinoma in 20 and melanoma in 8 patients, respectively. Six patients had been treated with RT during initial therapy after primary diagnosis, and IMRT was performed for the treatment of tumor progression as re-irradiation. Results: Overall survival rates were 96% at 1 year, 90% at 3 years. Calculated from the initiation of IMRT as primary radiotherapy, survival rates at 1 and 3 years were 95% and 80%. In six patients IMRT was performed as re-irradiation, and survival rate calculated from re-irradiation was 63% at 1 year. Local control rates were 85% at 1, 81% at 2 and 49% at 3 years after primary RT and 50% at 1 year after reirradiation. Distant metastases-free survival in patients treated with IMRT as primary RT was 83% after 1 and 64% after 3 years. For patients treated as primary irradiation with IMRT, the distant control rate was 83% at 1 year and 0% at 2 years. No severe radiation-induced side-effects could be observed. Conclusion: IMRT for tumors of the paranasal sinuses is associated with very good tumor control rates. Treatment-related acute and long-term toxicity can be minimized as compared to historical results with conventional RT.
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Radiation Oncology 2006, 1:23
Introduction Tumors of the paranasal sinuses (PNS) and nasal cavity are relatively rare, accounting for about 3–5% of all head and neck tumors; they are commonly associated with a poor prognosis [1,2]. Their incidence amounts to about 0.5% of all malignant diseases, and they show a wide variety of histologic subtypes [3]. The presence of air filled spaces permits silent growth of these tumors, and symptoms often occur only after the tumor has reached a considerable volume. Therefore, the majority of patients presents with advanced tumors, often extending into the skull base in close vicinity to sensitive risk structures such as optic nerves, chiasm, eyes and brain stem [4-6]. The primary treatment of choice is an aggressive surgical approach, followed by postoperative radiotherapy (RT) [7,8]. Due to the complexity of the anatomy and the proximity of these neoplasms to critical normal tissue structures radical surgery is often not possible [9-14]; furthermore, RT is associated with a high risk of treatment-related toxicity [15-17]. In the past, chronic toxicity to the optic system was of major concern, with RTinduced blindness rates of up to 37% [17-19]. Furthermore, underdosage in regions of risk were a major concern with conventional RT techniques. With modern high-precision RT-techniques such as Intensity Modulated Radiotherapy (IMRT), it is possible to increase the dose to defined target volume while reducing the dose to limiting organs at risk (OAR) to preserve organ function and subsequently quality of life. Furthermore, it is possible to improve dose conformality to the target volume with this technique as compared to conventional conformal RT techniques. Previous clinical results published from our institution have shown that IMRT can be applied safely and effectively in patients with tumors of the PNS [20]. However, these results were confined to a small number of patients only with a short follow-up time. The present study retrospectively evaluates the results of IMRT in 46 patients with carcinomas of the PNS, with special respect to treatment related acute and chronic toxicity.
Patients and methods Patients' characteristics Between January 1999 and October 2005, we treated 46 patients with histologically proven tumors of the PNS with IMRT. All patients were followed regularly after treatment.
Patients' characteristics are summarized in table 1. Histological classification included squamous cell carcinoma
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Table 1: Patient and disease characteristics of 46 patients with paranasal sinus carcinomas treated with IMRT
N (%) Gender female male Histology Adenocarcinoma Squamous Cell Carcinoma Adenoid-cystic Carcinoma Melanoma other Primary tumor site Maxillary sinus Ethmoidal sinus Sphenoid sinus Nasal cavity Tumor stage T1 T2 T3 T4 Nodal stage N0 N1 N2 Nx
18 (39%) 28 (61%) 8 (17.4%) 6 (13%) 20 (43.4%) 8 (17.4%) 4 (8.8%) 22 (47.8%) 4 (8.7%) 4 (8.7%) 16 (34.8%) 2 (4%) 3 (7%) 11 (24%) 30 (65%) 34 (74%) 6 (13%) 1 (2%) 5 (11%)
(SCC) in 6, adenocarcinoma (AC) in 12, adenoidcystic carcinoma (ACC) in 20 and melanoma in 8 patients. Patients with benign tumors such as inverted papilloma and with palate or skin primary tumors with secondary invasion of the sinuses and the nose were excluded from the analysis. Accordingly, pediatric sarcomas and esthesioneuroblastomas invading the PNS were not included. The tumor site was determined from the epicenter of the disease, as determined at the time of diagnosis or, more rarely, from an analysis of the clinical, radiologic or operative data. The sub site of origin was the maxillary sinus in 22 patients, the sphenoid sinus in 4, the ethmoidal sinus in 4 patients, and the nasal cavity in 16 patients, respectively. All patients were staged according to the 2002 TNM classification system [21]. Five patients presented with T1/ T2 tumors, 11 with T3 and 30 patients with T4 tumors, respectively. Six patients (13%) presented with intracranial invasion of the tumor; in 11 patients (24%) the orbit was infiltrated. Six out of 46 patients (13%) had been treated with RT during initial therapy after primary diagnosis, and IMRT was performed as re-irradiation for the treatment of tumor progression.
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Radiation Oncology 2006, 1:23
Treatment planning All patients were treated with IMRT using the step-andshoot approach [22]. For treatment planning, patients were fixed in an individually manufactured precision head mask made of Scotch cast® (3 M, St.Paul, Minneapolis, MN), allowing a treatment setup accuracy of 1–2 mm [23]. If treatment of the lymph nodes was required patients were additionally positioned with an individually fixed vacuum pillow in order to immobilize the neck and thorax. With this immobilization system attached to the stereotactic base frame, we performed contrastenhanced CT- and MRI-images under stereotactic conditions, with a slice thickness of 3 mm. We scanned the whole treatment region with a superior and inferior margin of at least 3 cm.
After stereotactic image fusion based on the localizerderived coordinate system [24,25], all critical structures including the optic nerves, chiasm, brainstem and eyes as well as the target volumes were defined on each slice of the three-dimensional data cube. The Gross Tumor Volume (GTV) was defined as the macroscopic tumor visible on CT- and MRI-scans. For the clinical target volume (CTV) a generous margin was added according to the typical pathways for microscopic spread and the anatomical relationship of adjacent structures. Generally, the CTV consisted of the resection cavity, all PNS completely or partially invaded, adding a safety margin of 3–5 mm. No elective RT of the cervical lymph nodes was performed. If treatment of the local lymph nodes was necessary, they were defined as a part of the CTV. Inverse treatment-planning was performed using the KonRad software developed at the German Cancer Research Center (dkfz), which is connected to the 3D planning program VIRTUOS to calculate and visualize the 3D dose distribution. With the KonRad planning programme, dose constraints and penalties for the target volumes as well as the organs at risk must be defined prior to starting the optimization process. The couch, gantry and collimator angles as well as the number of beams and intensity levels can be varied. Treatment planning has been described in detail previously [20,26-28]. Treatment was delivered by a Siemens accelerator (Primus, Siemens, Erlangen, Germany) with 6 or 15 MV photons using an integrated motorized multileaf collimator (MLC) for the step-and-shoot technique automatically delivering the sequences. The total doses were prescribed to the median of the target volume, meaning 50% of the target volume receives 100% of the dose. The median target volume was chosen for dose prescription since is represents the majority of the defined target volume.
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For dose prescription we adhered to the tolerance doses of each organ at risk; dose constraints were set at 27 Gy for the parotid, 54 Gy for the optic nerves, chiasm and brain stem and 45 Gy for the spinal cord. Dose prescription was performed, with respect to these tolerance doses, after plan calculation and analyses of the dose volume histogram (DVH). A summary of the DHV data is provided in table 2. For patients treated with IMRT as adjuvant RT after surgery, the median total dose applied was 64 Gy in a median fractionation of 2 Gy (range 1.8 – 2.2 Gy). A median total dose of 54 Gy was prescribed to the CTV, and a median dose of 64 Gy was prescribed to the GTV as a boost. For irradiation of the lymph nodes, a median dose of 54 Gy was applied. In 6 patients IMRT was performed as re-irradiation with a median dose of 46 Gy in a median fractionation of 2 Gy (range 1,8 Gy – 2 Gy). Prior to IMRT, a median total dose of 62 Gy had been applied using conventional RT.
Table 2: Summary of the DVH-data
Characteristics Boost(CTV) Dmed (Gy) V>30% (%) V30% (%) V30% (%) V30% (%) V30% (%) V30% (%) V
