1 Charles Poole April Case Study April 30, 2012 Evaluation of Whole-Field and Split-Field Intensity Modulation Radiation Therapy (IMRT) Techniques in Head and Neck Cancer Abstract: Introduction: This study aims to evaluate the treatment planning techniques of whole-field and split-field intensity modulation radiation therapy (IMRT) in treatment of head and neck cancers. Implementing an IMRT technique in the treatment of head and neck cancers allows for the utilization of the homogeneous dose distribution characteristic of IMRT to escalate dose to the tumor volumes while limiting the dose to the organs at risk (OR). Case Description: The treatment planning techniques of whole-field and split-field IMRT will be demonstrated in the following three case studies. For Patient 1 and Patient 3, a split-field IMRT technique will be evaluated which utilized an upper head and neck IMRT with static bilateral supraclavicular fields in conjunction with ipsilateral static boost fields. Patient 2 will demonstrate a whole-field IMRT technique that utilized IMRT throughout the whole head and neck region including the lower supraclavicular neck area. Conclusion: All plans were evaluated by the radiation oncologist for adequate dose coverage to the target areas. Each plan was evaluated individually based on visualization of the isodose line coverage to the gross tumor volume (GTV), the clinical tumor volume (CTV) and a dose volume histogram. The OR volumes were also evaluated by the radiation oncologist. In all studies, the larynx D mean and the dose gradient at the match line in the low neck region were used for comparisons between the two IMRT techniques. The split-field IMRT technique results in lower larynx dose when compared with a whole-field IMRT technique and is recommended in patients that do not have extensive disease involving the larynx. The whole-field IMRT technique is recommended in patients that have extensive disease involving the larynx. Key Words: Head and neck cancer, Intensity modulation, Whole-field technique, Split-field technique
2 Introduction: Radiation therapy for the treatment of head and neck cancer has continued to advance and develop over the last several years and is considered the main non-surgical treatment for squamous-cell carcinoma of the head and neck region. 1 The conventional radiation therapy approach in the treatment of head and neck cancers typically consisted of a three-field technique. 2 The three fields consisted of parallel-opposed lateral beams which included the upper neck primary tumor and draining lymphatics. 2 A third anterior field encompassed the lymphatic drainage of the lower neck and had a safety block to shield the larynx and spinal cord at the match line. 2 In treating head and neck cancer, conventional fields did not spare normal tissue and were associated with several side effects, some severe and even permanent. 3 These side effects lead to a poor quality of life after treatment. 3 More recent advances in radiation therapy such as the use of intensity modulated radiation therapy (IMRT) have demonstrated that normal tissues in the head and neck region can be spared more effectively. Studies have shown that the use of IMRT in the treatment of head and neck cancer significantly improves a patients quality of life by reducing the incidence of xerostomia through sparing the parotid and major salivary glands. 1 Further benefits of IMRT are demonstrated by the ability to provide conformal dose distributions to target volumes minimizing doses to normal tissues in the head and neck region. In radiotherapy treatment of head and neck cancers when the primary diagnosis is above the larynx, there are two treatment options which utilize (IMRT) techniques to treat the lower level lymphatic regions: treat the entire neck with IMRT or match an IMRT plan with static conventional low neck fields. 4 These two techniques have advantages and disadvantages associated with each. The whole-field IMRT technique is simpler to plan and the dose is more homogeneous throughout the target volume and this technique avoids the hot and cold spots associated with setup errors at the match line. 4 One of the disadvantages of the whole-field IMRT technique is the increased dose to the larynx, causing laryngeal edema, which may present long term speech and swallowing problems. 5 In contrast, an advantage with incorporating a splitfield IMRT technique, the dose to the larynx may be decreased by utilizing a larynx block and the IMRT plan will often yield superior results. 4 However, the split-field IMRT technique may cause dose inhomogeneities or hot and cold spots, as well as setup errors at the match line throughout the whole course of radiotherapy treatment which may cause failures or
3 complications. 5 In addition, the split-field technique is not recommended if there is gross adenopathy at the level of the larynx due to the risk of regional failure. 5 The challenges a medical dosimetrist encounters when utilizing either IMRT techniques in a head and neck treatment plan are maintaining adequate prescription coverage to the tumor volumes, limiting dose to the OR, and controlling dose escalation within the target volumes. In addition, if a split-field technique is incorporated the medical dosimetrist must optimize the prescription dose coverage between the two field sets extending through the match line transition area. The junction at the match line can lead to significant hot or cold spots which translate into over-dosing or under-dosing the match line area. Errors in setup at the match line transition area can result in significant dosimetric consequences. Daily accuracy must be practiced throughout the course of radiotherapy treatment to avoid possible recurrence of disease in this match line area if under dosage occurs or an excessive over dose to the larynx or spinal cord if an overlap of fields is present. The three case studies demonstrate the use of an IMRT technique in the treatment of head and neck cancer. Two case studies incorporated a split-field IMRT technique and one case study incorporated a whole-field IMRT technique. Typical head and neck radiotherapy fractionation schemes were used in each of the three case studies. The radiotherapy target doses prescribed in IMRT portion of these three case studies ranged from 66Gy to 70Gy. The IMRT dose painting feature was utilized to provide adequate prescription dose around the appropriate target volumes. In the cases which utilized a split-field IMRT technique, dose to the bi-lateral low neck supraclavicular region was delivered by static fields with additional static fields for ipsilateral neck boosts. The bi-lateral low neck supraclavicular dose in two of these case studies was 46Gy with ipsilateral boost dosages ranging from 8Gy to 14Gy for a total dose of 54Gy to 60Gy. In these three case studies, one case study demonstrates a whole-field IMRT technique and the remaining two case studies illustrate a split-field IMRT technique in the radiotherapy treatment of head and neck cancer. Each case study illustrated a head and neck cancer treatment regimen utilizing these techniques. Plans were evaluated individually based on cumulative dose volume histogram (DVH), the percentage of CTV and GTV coverage at 100% of the prescription dose (V 100 ), the mean dose (D mean ) to the right and left parotid glands, and the larynx max dose (D max ) and mean dose (D mean ).
4 Methods and Materials: Patient Selection The criteria for each case study that was selected was categorized by one of two IMRT techniques for the treatment of head and neck cancer. Each case was chosen based on whether the patient was having a whole-field IMRT or a split-field IMRT technique for treatment. Patient 1, a 33 year old female, diagnosed with squamous cell carcinoma of the oropharynx involving the right tonsillar fossa was treated definitively with a split-field IMRT technique to a dose of 66Gy and 60Gy. This technique incorporated upper head and neck IMRT fields treated in conjunction with low neck static fields utilizing two separate isocenters. Patient 2, a 29 year old female diagnosed with post surgical recurrence of a previous squamous cell carcinoma of the oral cavity involving the left tongue. This recurrence involved a left cervical level II lymph node and the left level IV lymph node region. The technique utilized for treatment in this case was a whole-field IMRT technique designed to treat both the upper head and neck target volumes and the low neck bilateral supraclavicular target volumes to doses of 70Gy, 66Gy, 60Gy, and 54Gy. This technique used one isocenter for treatment. Patient 3, a 69 year old male, diagnosed with squamous cell carcinoma of the oral cavity involving the right tongue was treated postoperatively with a split-field IMRT technique to doses of 60Gy and 54Gy. This technique also incorporated upper head and neck IMRT fields treated in conjunction with low neck static fields utilizing two separate isocenters. Patient Set-up Each patient underwent a computed tomography (CT) scan for simulation utilizing an Aquaplast mask for head and neck immobilization for radiation therapy. Patient 1 was CT simulated in the supine position with a large S-type Aquaplast IMRT mask on an S-type board. The patients head was supported on a C-type headrest and a knee sponge was placed under the knees for comfort. Patient 2 was CT simulated in the supine position with a large S-type Aquaplast IMRT mask on an S-type board. A bite block was inserted into the patient s mouth for immobilization. The patients head was supported with an A-type headrest and a knee sponge was placed under the patients knees for comfort. Patient 3 was CT simulated with a regular Aquaplast mask on an S- type board for immobilization. A bite block was place in the patient s mouth for immobilization.
5 The patients head was supported using an F-type headrest and a sponge was placed under the knees for comfort. In addition, each patients arm placement was on the abdomen holding a blue positioning ring for comfort. Target Delineation Once each patient was CT simulated, target delineation was completed using the Philips ADAC Pinnacle 3 treatment planning system (TPS) for radiation therapy planning. Patient 1 had undergone a positron emission tomography (PET) scan that was fused with the CT simulation scan to assist the radiation oncologist in contouring the gross tumor volume (GTV). The GTV was contoured from the positive glucose uptake by the disease in the right tonsillar region and involved the right cervical lymph nodes. In addition, the radiation oncologist contoured a clinical target volume (CTV) which represented the oropharynx and the right upper cervical lymphatics which were labeled CTV66 and a CTV60 which represented the left upper lymphatics. The GTV and CTV66 were expanded by 0.3 cm in all directions and labeled GTV+3mm and PTV66 respectively. The radiation oncologist requested that CTV60 receive no additional expansion. Each of these volumes were reviewed and adjusted by the radiation oncologist for overlap with anatomical barriers and normal tissues. The PTV66 and CTV60 were adjusted 0.4 cm inside the skin surface to avoid excessive dose to the skin surface. The spinal cord, brainstem, right and left parotids, oral cavity, esophagus, larynx, and mandible were contoured as organs at risk (OR) by the medical dosimetrist and reviewed by the radiation oncologist. Patient 2 had undergone a diagnostic CT scan with contrast and a PET scan that was fused with the CT simulation scan. These two datasets assisted the radiation oncologist in delineating the recurrent mass in the left cervical neck area, as well as identifying the left and right cervical neck lymph nodes suspected for malignancy on the CT simulation scan. A GTV was contoured which represented a large recurrent mass in the left cervical neck and suspicious malignant right and left cervical lymph nodes. Additional bilateral cervical neck target volumes were delineated by the radiation oncologist and labeled CTV66, CTV60, and CTV54. All volumes were expanded by 0.3 cm and labeled as PTV s accordingly. Each expanded volume was reviewed by the radiation oncologist to assess the overlap with anatomical boundaries and adjustments were made inside the skin surface to avoid excess skin dose. The medical dosimetrist contoured the
6 OR such as the spinal cord, brain stem, right and left parotid glands, mandible, oral cavity, larynx, and esophagus. Each of the OR were reviewed and adjusted by the radiation oncologist. Patient 3 had undergone a diagnostic CT scan that was fused with the CT simulation scan to assist the radiation oncologist in contouring a CTV60 and CTV54. Each CTV was expanded by 0.3 cm in all directions and labeled as PTV60 and PTV54 respectively. The PTV s were reviewed by the radiation oncologist to assess the overlap with anatomical boundaries and adjustments were made to the PTV s inside the skin surface to avoid excess skin dose. The medical dosimetrist contoured the OR such as the spinal cord, brain stem, right and left parotids, mandible, oral cavity, larynx, and esophagus. Each of the OR s were reviewed and adjustments were made by the radiation oncologist. Treatment Planning The dose prescriptions and planning parameters for the three head and neck case studies are presented in Table 1. Patient 1 utilized a split-field IMRT technique with an upper head and neck IMRT prescription dose of 66Gy in 33 fractions. The radiation oncologist outlined the dose objectives for the GTV+3mm, PTV66, and CTV60 in the upper head and neck IMRT plan. The dose objectives for this case study directed the GTV+3mm to receive a dose of 70Gy, the PTV66 to receive a dose of 66Gy, and the CTV60 to receive a dose of 60Gy from one prescription incorporating the dose painting technique of IMRT. A bi-lateral low neck supraclavicular prescription dose of 46Gy in 23 fractions and a right-sided low neck boost prescription dose of 14Gy in 7 fractions were delivered. Therefore, the composite dose to the right side low neck region was 60Gy. The bi-lateral supraclavicular fields and the ipsilateral boost fields utilized static beams for delivery. The initial OR objectives included: the spinal cord maximum dose was to be < 46Gy, the right and left parotid mean doses < 26Gy, the oral cavity maximum dose < 55Gy, the esophagus maximum dose < 50Gy, the mandible maximum dose < 70Gy, the brain stem maximum dose < 50Gy, and the larynx maximum dose < 50Gy. These target and OR planning objectives were specified in the IMRT optimizer in the TPS and an IMRT plan was generated (Figure 1). Patient 2 utilized a whole-field IMRT technique with an IMRT dose prescription of 70Gy in 35 fractions. The radiation oncologist outlined the dose objectives for the GTV+3mm, CTV66+3mm, CTV60+3mm, and the CTV54+3mm. The dose objectives for this case study
7 directed the GTV+3mm to receive 70Gy and each CTV receive its corresponding dose from one prescription incorporating the dose painting technique of IMRT. The initial OR objectives for this case study included: the right parotid mean dose < 23Gy, the oral cavity maximum dose < 55Gy, the esophagus maximum dose < 50Gy, the mandible maximum dose < 72Gy, the brain stem maximum dose < 50Gy, and the spinal cord maximum dose < 44Gy. These target and OR planning objectives were specified in the IMRT optimizer in the TPS and an IMRT plan was generated (Figure 2). Patient 3 utilized a split-field IMRT technique with and upper head and neck IMRT prescription dose of 60Gy in 30 fractions. The radiation oncologist outlined the dose objectives for the PTV60 and PTV54 in the upper head and neck IMRT plan. The dose objectives for this case study directed the PTV60 to receive a dose of 60Gy and the PTV54 to receive a dose of 54Gy from one prescription which also utilized the IMRT dose painting technique. A bi-lateral low neck supraclavicular prescription dose of 46Gy in 23 fractions and a right-sided low neck boost prescription dose of 8Gy in 4 fractions were delivered. Therefore, the composite dose to the right side low neck region was 54Gy. The bi-lateral supraclavicular fields and the ipsilateral boost fields utilized static beams for delivery. The initial OR objectives included: the left parotid gland mean dose < 25Gy, the right parotid gland mean dose < 30Gy, the brain stem maximum dose < 40Gy, the spinal cord maximum dose < 44Gy, the larynx maximum dose < 55Gy, and the esophagus maximum dose < 40Gy. These target and OR planning objectives were specified in the IMRT optimizer in the TPS and an IMRT plan was generated (Figure 3). Plan Analysis & Evaluation In each of these case studies the medical dosimetrist optimized the various target volumes with a planning PTV in the IMRT optimizing module of the TPS. In order to accurately evaluate the prescription dose coverage to the various volumes used in the IMRT dose painting technique in these case studies, the GTV s and CTV s in each study were used to report dose coverage. In order to accurately analyze target volume coverage, the PTV s coverage s were not reported as a result of their expansions entering into the buildup regions near the skin surface. Therefore, the DVH will not accurately or clearly reflect PTV coverage s. The GTV s and CTV s of each case study will be reported for dose coverage due to the inaccuracies of the PTV expansions into the buildup regions near the skin surface. A summary of the percentage of CTV and GTV coverage
8 at 100% of the prescription dose (V 100 ), the mean dose (D mean ) to the right and left parotid glands, and the larynx max dose (D max ) and mean dose (D mean ) are presented in Table 2. For Patient 1, the evaluation of the split-field IMRT technique demonstrated that not all of the cumulative dose objectives and constraints were achieved. The percentage of GTV70, CTV66, and CTV60 at 100% of each prescription dose (V 100 ) was 98.1%, 98.1%, and 93.8% respectively. The spinal cord D max was 45.6Gy, the right parotid gland D mean was 41.6Gy, and the left parotid gland D mean was 25.8Gy. The larynx D mean was 18.6Gy and the D max was 49.6Gy. The upper head and neck IMRT prescription in this plan was normalized to 101% while the bi-lateral low neck supraclavicular region and the right low neck boost region were normalized to 100% accordingly. The right parotid gland D mean was unachievable for the initial dose constraint due to overlap of the target volumes within the right parotid gland. The radiation oncologist reviewed the volume overlaps with the right parotid and accepted a higher D mean dose to the right parotid gland. For Patient 2, the evaluation of the whole-field IMRT technique illustrated some of the cumulative dose objectives and constraints were not achieved. The V 100 of GTV70 was 98.2%, CTV66 was 97.1%, the CTV60 was 93.4%, and the CTV54 was 98.5%. The spinal cord D max was 42.4Gy, the right parotid gland D mean was 19Gy, and the left parotid gland D mean was 71.0Gy. The larynx D mean was 64.4Gy and the D max was 72.2Gy. The whole-field IMRT prescription was normalized to 98%. The left parotid gland D mean was not achievable due to recurrence of tumor which involved the gland. The tumor volume totally encompassed the left parotid gland. The larynx dose was higher in this patient due to tumor involvement in the larynx. For Patient 3, the evaluation of the split-field IMRT technique demonstrated that all of the cumulative dose objective and constraints were achieved. The V 100 of CTV60 was 96.2% and the CTV54 was 92.6%. The spinal cord D max was 40.2Gy, the right parotid gland D mean was 30.0Gy, the left parotid gland D mean was 24.9Gy. The larynx D mean was 37.7Gy and the D max was 63.3Gy. The upper head and neck IMRT prescription in this plan was normalized to 99% while the bilateral low neck supraclavicular region and the right low neck boost region were normalized to 100% accordingly. The IMRT technique was able to spare both the right and left parotid glands however; the radiation oncologist requested a higher mean dose to the right parotid gland in order to maintain adequate tumor dose coverage on the ipsilateral side.
9 With the split-field IMRT technique in Patient 1 and Patient 3, the DVH reflected significant sparing of the larynx in terms of D mean compared to Patient 2 with the whole-field IMRT technique. The parotid gland and spinal cord doses did not result in any significant changes when comparing the two techniques. The parotid glands D mean in each of the case studies were the result of clinical decisions concerning dose coverage s to the nearby tumor volumes made by the radiation oncologist. For Patient 1 and Patient 3, the right parotid gland D mean was greater than the left parotid gland dose due to the right-sided tumor volume. For Patient 2, the left parotid gland D mean was greater due to recurrent tumor volume in the left parotid gland. The doses to all the other OR s are comparable between the two techniques. The dose gradient at the match line is more homogeneous in the whole-field IMRT technique compared with the dose gradient of the split-field IMRT technique. An increase or decrease in the dose gradient at the match line may result in an under-dose or over-dose to the patient. Results and Discussion: There are several comparisons and contrasts in the literature for whole-field IMRT and split-field IMRT techniques for treating head and neck cancer. The considerations a medical dosimetrist encounters in the clinical setting when utilizing these IMRT technique for the head and neck region are daily patient alignment and position of the shoulders, daily setup error, and the beam arrangement that will be used for treatment. It can be challenging to align the shoulders and the bi-lateral low neck supraclavicular fields on a daily basis. The use of a large IMRT mask versus a regular mask can aid in the positioning and alignment every day. Daily imaging of the low neck can be challenging as well. The medical dosimetrist must consider the daily setup variables associated with these two techniques. The cases studies represented two different techniques in head and neck IMRT treatments. The whole-field IMRT technique is recommended if low neck lymph nodes are present and are greater than 3.0 cm or if the glottic larynx is part of the target volume. 5 The whole-field IMRT technique is preferred for hypopharynx or laryngeal cancers. 5 The split-field IMRT technique is recommended for nasopharyngeal or oropharyngeal primary cancers to limit dose to the glottic larynx. However, it is important to note that both techniques are good for treating subclinical disease. 5 The main advantage in the split-field IMRT technique is the ability to lower laryngeal doses. It is well documented in literature that reducing dose to the larynx and the swallowing
10 structures in the low neck may result in having a better long term outlook for patients whom have undergone head and neck radiotherapy treatment.
Figure 1: Patient 1 dose distribution, split-field IMRT with match line, and DVH. 11
Figure 2: Patient 2 dose distribution, whole-field IMRT, and DVH. 12
Figure 3: Patient 3 dose distribution, split-field IMRT with match line, and DVH. 13
14 Table 1: Prescription and Treatment Planning Parameters. Prescription and Treatment Planning Parameters Case Study Patient 1 Patient 2 Patient 3 Site Right Tonsil Left Tongue (recurrent) Prescription Right Tongue (postoperative) Beam Energy 6MV and 15MV 6MV 6MV and 15MV Fractionation Standard Standard Fractionation Fractionation Dose to GTV 70Gy in 33 fractions 70Gy in 35 fractions Standard Fractionation Dose to CTV 1 66Gy in 33 fractions 66Gy in 35 fractions 60Gy in 30 fractions Dose to CTV 2 60Gy in 33 fractions 60Gy in 35 fractions 54Gy in 30 fractions Dose to CTV 3 Dose to Bi-Lateral Low Neck Dose to Low Neck Boost 54Gy in 35 fractions 46Gy in 23 fractions 14Gy in 7 fractions Treatment Planning Parameters 46Gy in 23 fractions 8Gy in 4 fractions Planning Technique Beam Arrangements IMRT / Split Field IMRT IMRT / Split Field 9 co-planar beams / 2 AP and 2 PA beams Gantry Angles 200, 240, 280, 320, 0, 40, 80, 120, 160 / 0 and 180 9 co-planar beams 9 co-planar beams / 4 AP beams 200, 240, 280, 320, 0, 40, 80, 120, 160 200, 240, 280, 320, 0, 40, 80, 120, 160 / 0 Note: The couch and collimator was 0 for all beams except for Patient 1 the collimator was 90.
15 Table 2: Plan Analysis and Evaluation. Plan Analysis and Evaluation Patient 1 Split Field Patient 2 Whole Field Patient 3 Split Field V 100 (%) D max (Gy) D mean (Gy) V 100 (%) D max (Gy) D mean (Gy) V 100 (%) D max (Gy) D mean (Gy) GTV 98.1 98.2 CTV 1 98.1 97.1 96.2 CTV 2 93.8 93.4 92.6 CTV 3 98.5 Right Parotid 41.6 19.0 30.0 Gland Left Parotid 25.8 71.0 24.9 Gland Larynx 49.6 18.6 72.2 64.4 63.3 37.7
16 References 1. Nutting C, Morden J, Hall E, et al. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. The Lancet Oncology. 2011;12(2):127-136. 2. Dabaja B, Salehpour M, Garden A, et al. Intensity-modulated radiation therapy (IMRT) of cancers of the head and neck: comparison of split-field and whole-field techniques. Int J Radiat Oncol Biol Phys. 2005;63(4):1000-1005. 3. Chao K, Ozyigit G, Tran B, Cengiz M, Dempsey J, Low D. Patterns of failure in patients receiving definitive and postoperative IMRT for head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2003;55(2):312-321. 4. Amdur R, Liu C, Li J, Mendenhall W, Hinerman R. Matching intensity-modulated radiation therapy to an anterior low neck field. Int J Radiat Oncol Biol Phys. 2007;69(2 Suppl):46-48. 5. Turaka A, Li T, Feigenberg S, et al. Use of a conventional low neck field (LNF) and intensity-modulated radiotherapy (IMRT): no clinical detriment of IMRT to an anterior LNF during the treatment of head-and neck-cancer. Int J Radiat Oncol Biol Phys. 2011;79(1):65-70.