1 Effectiveness of IMRT and VMAT for sparing the mandible, larynx, and parotid glands in oropharyngeal cancer treatment

Authors: Amanuel Negussie, B.S. R.T.(T), Nishele Lenards, M.S., CMD, R.T.(R)(T), FAAMD, James Schmitz, A.A.S., CMD, R.T.(T), and Joseph G. Lynch, CMD, R.T.(T)(MR) Abstract: Introduction: The aim of this study is to compare and contrast sparing of the mandible, larynx, and ipsilateral parotid gland in treatment of oropharyngeal cancer using IMRT and VMAT techniques. Case Description: A treatment with IMRT or VMAT using multiple boost techniques was demonstrated in the following 3 cases. Patient 1 represents a case of tonsil squamous cell carcinoma with 3 target volumes treated postoperatively using SEQ VMAT. Patient 2 represents a case of base of tongue squamous cell carcinoma with 2 target volumes treated definitively using SIB VMAT plus 3DCRT. Patient 3 represents a case of vallecular squamous cell carcinoma with 3 target volumes treated using SIB IMRT. Conclusion: Each case was individually evaluated on how well normal structures were spared and whether the plan met the objectives. The plans were evaluated based on RTOG and QUANTEC guidelines. Oropharyngeal cancer treatments using SEQ VMAT, SIB VMAT plus 3DCRT, and SIB IMRT have been demonstrated on how well the ipsilateral parotid, larynx, and mandible can be spared with optimal target coverage. Key Words: oropharyngeal cancer, organs at risk, IMRT, VMAT Introduction The anatomy of the oropharynx extends inferiorly to the hyoid bone and includes the base of tongue and tonsil. Oropharyngeal cancer commonly occurs in the base of tongue and tonsil and is less common in the soft palate and posterior pharyngeal wall. About 60% of oropharyngeal cancers are caused by human papilloma virus (HPV). 1 The management of oropharyngeal cancer is multidisciplinary, which may include surgery, radiation therapy, or chemotherapy. The type of treatment chosen for each patient may vary based on the stage and patients status. Radiation

2 therapy is one of the most important treatment approaches that can either be used as a definitive treatment or as an adjuvant postoperative treatment. Radiation therapy alone is a standard approach for early staged oropharyngeal tumors. 2 Radiation therapy alone or with chemotherapy is also a treatment of choice for HPV related oropharyngeal tumors. 1 Since oropharyngeal cancers are often approached with a curative intent and are treated with high dose radiation, normal organ preservation is essential. The presence of various radiosensitive structures in the head and neck region make treatment planning a difficult task. Advanced treatment techniques such as intensity modulated radiation therapy (IMRT) and volumetric modulated radiation therapy (VMAT) are becoming standard treatment methods due to the ability to reduce dose to normal structures. Even with these techniques, radiation therapy treatments can cause significant acute and late toxicities. Late reactions mainly include xerostomia, dysphagia, and osteonecrosis. 3 As a result, attention must always be given to the parotid glands, mandible, and larynx when planning oropharyngeal cancer treatments. Maintaining salivary flow by preserving salivary glands is fundamental in oropharyngeal cancer treatments. Studies from University of Michigan showed that IMRT can reduce contralateral parotid dose to 32% compared to 93% using traditional technique.4 According to a study by Blanco et al,5 patients with bilateral parotid mean dose greater than 25 gray (Gy) have poor salivary function; whereas, decreased xerostomia was recorded when one or both parotids received a mean dose less than 25 Gy. Although sparing the contralateral parotid is of utmost importance, the significance of sparing the ipsilateral parotid is debatable. 6 Current radiation therapy oncology group (RTOG) and quantitative analysis of normal tissue effects in the clinic (QUANTEC) guidelines require minimizing mean dose for parotid below 26 Gy (Table 1). 7,8 The incidence of osteonecrosis after oropharyngeal cancer treatment is 5-15% depending on the dose to mandible and patients dental hygiene. 3 This can be reduced by dental extraction and limiting the dose to the mandible to less than 60 Gy.3 A large number of patients who undergo surgery and radiation treatment for oropharyngeal cancer benefit from implant supported prosthesis. High dose radiation to the anterior mandible can lead to prosthesis implant failure to this region.9 Compared to other head and neck sites, the dose to the mandible is higher in oropharyngeal cancer treatments. 10 Generally, risk of osteonecrosis is dependent on the volume

3 of mandible irradiated to high radiation dose. RTOG guidelines recommend limiting the maximum dose for the mandible to below 66 Gy (Table 1). Sparing the larynx is also essential in oropharyngeal cancer treatments to prevent dysphagia and aspiration. Intensity modulated radiation therapy (IMRT) can be used in two different methods to achieve this: junctioned IMRT (J-IMRT) and whole field IMRT (WF-IMRT). In J-IMRT, the upper portion of the target is treated with IMRT matched to an anterior (AP) field with a laryngeal block to treat the lower portion of the target.11 In WF-IMRT, the entire target is treated with IMRT fields.11 Multiple studies have shown that WF-IMRT can significantly reduce the mean dose for larynx when compared to J-IMRT.11 QUANTEC recommends limiting the maximum dose for the larynx to below 66 Gy and the mean dose to below 50 Gy (Table 1). RTOG recommends the maximum dose to be kept below 45 Gy (Table 1). Case Description Patient selection Patient 1 is a 61 year old male with HPV positive stage T1 (stage 1 primary tumor) N2 (stage 2 regional lymph nodes) M0 (No metastasis) squamous cell carcinoma of the left tonsil. A positron emission tomography (PET)/CT demonstrated involvement in the superficial lobe of right parotid gland, lymph node in the tail of right parotid, intraparotid lymph nodes within the tail of the left parotid, and left laryngeal tonsil. The patient was initially treated with tonsillectomy and neck dissection. Radiation therapy was given as an adjuvant treatment following his surgery. Patient 2 is an 82 year old male with a stage T3 (stage 3 primary tumor) N2 M0 squamous cell carcinoma of base of tongue (BOT). A magnetic resonance imaging (MRI) of the neck demonstrated a soft tissue mass at the base of the tongue centered to the left of midline, but appearing to cross the midline. There was also extensive lymphadenopathy bilaterally including level I through IV and VI. The patient was not a surgery candidate due to his respiratory condition. Therefore, radiation therapy was given as a definitive treatment. A study by Chen et al12 showed that definitive radiation therapy without chemotherapy can provide higher rate of 3 year overall survival, locoregional control, and distant metastasis-free survival for patients with HPV positive head and neck cancer.

4 Patient 3 is a 66 year old male with HPV positive stage III T1 N1 (stage 1 regional lymph nodes) M0 squamous cell carcinoma of the left vallecula. A workup CT scan of the neck revealed an irregular enhancing mass in the left neck anterior to the left sternocleidomastoid. A PET scan also demonstrated a level II lymph node of the left neck. The patient was recommended a concurrent chemoradiation treatment. Patient Set-up All three patients were scanned in a supine position on a head support. Patient 2 was positioned with the head and chest slightly inclined using board due to his inability to lay flat on the CT couch. In all three cases, an aquaplast mask was used to immobilize the head, neck, and shoulders. A shoulder strap was used for Patients 2 and 3 to further ensure that the shoulders were pulled away from the treatment area. A bite block was used for Patient 1. In patients treated for a base of tongue where the contralateral neck is clinically negative, bite blocks should not be used in order to spare the contralateral parotid gland.12 A wire was placed on the surgical scar for Patients 1. Target Delineation The Eclipse treatment planning system (TPS) version 10 was used for Patients 1 and 2. The Pinnacle TPS version 9 was used to plan the treatments for Patient 3. The CT scans were obtained with General electric (GE) lightspeed CT unit for Patients 1 and 2 and Philips large bore 16 slice CT unit for Patient 3. The images were taken at 2.5 mm for Patients 1 and 2, and 3 millimeter (mm) slices for Patient 3. The variation in slice thickness is due to difference in departmental preferences. For Patient 1, no diagnostic images were fused with the planning CT scan. The medical dosimetrist contoured the eyes, lenses, lungs, cochlea, optic nerves, mandible, shoulders and larynx. The radiation oncologist contoured the parotid glands, oral cavity, optic chiasm, pituitary gland, submandibular gland, thyroid, and the target volumes. The PTVs included: PTV 50 (the PTV receiving 50 Gy), PTV 64 (the PTV receiving 64 Gy), and PTV 70 (the PTV receiving 70 Gy). For Patient 2, the planning CT was fused with a diagnostic MRI of the neck. The normal structures contoured by the medical dosimetrist were the brain, brainstem, eyes, lenses, lungs,

5 cochlea, optic nerves, mandible, shoulders, and larynx. The radiation oncologist contoured the parotid glands, optic chiasm, oral cavity, and the targets. The PTVs included PTV 50 and PTV 70. Two CT scans were obtained for Patient 3, with and without IV contrast (Visipaque). The scan without contrast was used as a primary image to plan the treatment. The CT scan with contrast and the PET scan were fused with the primary image. The structures contoured by the medical dosimetrist included the spinal cord, brainstem, mandible, and eyes. The radiation oncologist contoured the parotid glands, esophagus, larynx, oral cavity, and the target volumes. The target volumes included PTV 56, PTV 63, and PTV 70. Treatment Planning The dose prescription and planning parameters of each case are presented in Table 2. The dental artifacts were contoured and assigned a density equivalent to water for all patients. Metal artifacts can distort dose distribution by creating cold and hot spots. This correction method helped reduce such complication. The treatment plan for patient 1 was designed to target three PTVs using sequential (SEQ) VMAT technique. PTV1 was prescribed to 50 Gy targeting the bilateral nodal chains. PTV 2 was prescribed to 64 Gy targeting the primary tumor bed plus regions of grossly involved lymphadenopathy. PTV3 was prescribed to 70 Gy targeting regions that are high risk for recurrence. The initial plan for PTV 50 included three arc fields, two in clockwise (CW) direction and one in counter clockwise (CCW) direction. The plans for PTV 64 and PTV 70 included two arcs, in CW and CCW direction. Due to weight loss and change in anatomical contour, the patient was re-simulated after the completion of the initial treatment. All three plans were carried out with a similar approach. The PTVs were enlarged by 1 mm in all directions for optimization purpose. This allowed the medical dosimetrist to effectively distribute the prescribed dose to the entire PTV. A 1 cm wide ring was constructed 2 cm away from the PTVs. The OR that overlapped with the PTVs were cropped 3 mm away from the PTV for optimization purpose. This included the parotids, mandible, and oral cavity for PTV 50; the left parotid and mandible for PTV 64; and left parotid for PTV 70. This technique effectively minimized the dose to the OR without affecting the PTV coverage. Each plan was optimized with objectives set for

6 the enlarged PTV, the ring, parotids, mandible, oral cavity, spinal cord PRV, brain stem, and shoulders. The treatment plan for patient 2 was designed to target two PTVs using SIB VMAT technique, followed by a boost to a third PTV using three-dimensional conformal radiation therapy (3DCRT) technique. PTV1 was prescribed to 50 Gy targeting the bilateral nodal chains. PTV 2 was prescribed to 70 Gy targeting the tumor and involved lymph nodes. The initial plan targeted PTV 50. The treatment was planned using VMAT technique with three arcs, two in CW direction and one in CCW direction. PTV 50 was enlarged by 1 mm in all directions for optimization purpose. A 1 cm wide ring was constructed 2 cm away from the PTVs. The OR that abutted with the target were cropped 3 mm away from PTV 50. This included mandible, parotids, and oral cavity. The plan was optimized with objectives set for the enlarged PTV 50, the ring, parotids, mandible, oral cavity, spinal cord PRV, brain stem, and shoulders. The boost for PTV 70 was planned using 3DCRT with right anterior oblique (RAO) and left anterior oblique (LAO) beams. The collimator was rotated to 55o for the RAO and 33o for the LAO to exclude the spinal cord from the treatment field. The treatment fields were constructed with 1cm margin around PTV 70. A 45o wedge was used for the RAO field with the heel positioned anteriorly. The weighting for the RAO and LAO beams was adjusted to 51% and 49%. The treatment for patient 3 was planned targeting three PTVs using SIB IMRT technique. PTV 1 was prescribed to 56 Gy and targeted low risk nodal regions. PTV 2 was prescribed to 63 Gy and targeted high risk nodal regions. PTV3 was prescribed to 70 Gy and targeted the gross tumor volume. The treatment was planned using SIB step-and-shoot IMRT technique. A 9-field equidistance beam arrangement was used. A PTV 63-70 and PTV 56-70 were constructed to detach each PTV with different dose level. The OR that overlapped with the target were cropped 3 mm away from PTV 54 for optimization purpose. This included the oral cavity, mandible, parotids, and larynx. The neck posterior to the spinal cord was contoured for optimization purpose. The inverse planning included clinical goals to PTV 56-70, PTV 63-70, PTV 70, spinal cord, spinal cord PRV, brain stem, brain stem PRV, parotids, larynx, oral cavity, posterior neck, and mandible. Plan Analysis & Evaluation

7 Traditionally, head and neck cancer patients were treated with parallel-opposed lateral photon fields. The spinal cord was blocked after 40 Gy and electron fields were used to boost the posterior neck. The oral cavity may have been blocked throughout the treatment and reduced photon fields were used to boost the gross tumor volume. An additional anterior photon field may have also been used to treat the supraclavicular nodes. IMRT and VMAT have enhanced the sparing of the parotids compared to the conventional treatments. However, the anterior mucosa and the posterior neck would be more exposed unless purposely spared by the planner. 13 In order to minimize the dose to the anterior mucosa, the oral cavity was contoured in all three patients and dose objectives were established. The posterior neck was contoured for patient 3, who was treated with IMRT. Dose objectives were set aiming to spare the posterior neck from 50% of the prescribed dose. In Patients 1 and 2, who were treated with VMAT, avoiding an entrance beam posteriorly spared the posterior neck. These approaches have allowed mapping out a plan that is effective in sparing the oral mucosa and posterior neck. The most notable difference between VMAT and IMRT is variation in monitor unit (MU) and treatment time. Various studies have proven that VMAT can provide lower MU per fraction with shorter delivery time. VMAT is also known to provide better dose conformity than IMRT. However, IMRT can generate plans with better dose homogeneity. 14 A study by Clemente et al15 showed that, in oropharyngeal cancers, higher larynx sparing can be achieved with IMRT but better ipsilateral parotid sparing can be achieved with VMAT. Another study by Teoh et al16 demonstrated lower contralateral parotid sparing can be achieved with VMAT than IMRT. The treatment for Patient 1 was planned with a goal to meet the QUANTEC guidelines. The ipsilateral parotid was spared with a mean dose of 16.4 Gy. For the larynx, the mean dose was met with 51 Gy. Although QUANTEC does not provide a dose limit for the mandible, the dose was minimized to a mean dose of 38.4 Gy and maximum dose of 65 Gy. This met the RTOG guidelines with a close margin. All targets were covered with the 95% isodose line and a maximum dose of 109% (Figure 2 and Table 3). The plan was acceptable to the physician since the parotid, larynx, and the OR were effectively spared. For patient 2, the QUANTEC guidelines were used as a guide for planning. The ipsilateral parotid gland was spared with a mean dose of 19.6 Gy. The dose constraints for the larynx were

8 not met. The mean dose was 69.4 Gy and the maximum dose was 72.9 Gy. The mean and maximum dose for mandible was 40.3 Gy and 69.3 Gy. These did not meet the RTOG guidelines. All targets were covered with the 95% isodose line and a maximum dose of 105% (Figure 3 and Table 3). The plan was acceptable to the physician since large volume of the mandible and larynx were overlapped with the targets. The treatment for Patient 3 was planned with a goal to meet the RTOG guidelines. The ipsilateral parotid gland was spared with a mean dose of 20 Gy. The maximum and mean doses of the larynx were 41.4 Gy and 53.5 Gy. These met both the QUANTEC and RTOG guidelines. The mean and maximum dose to mandible was 45.4 Gy and 74.6 Gy, which did not meet the RTOG guideline. All three PTVs were successfully covered with 95% of the prescribed dose (Figure 5). The plan was finalized with a maximum dose of 109% (Table 3). The constraints for the remaining OR including the brainstem, oral cavity, and spinal cord were met for all patients. The ipsilateral parotid gland was spared with a mean dose less than 20 Gy for all cases. A study by Clemente et al15 showed that VMAT is better in sparing the ipsilateral parotid gland than IMRT. A similar outcome was seen in these three cases. The ipsilateral parotid was spared the most in Patient 1, where three separate VMAT plans were developed for each PTV. The ipsilateral parotid was spared the least in Patient 3, who was treated with SIB IMRT technique. This was because higher priority was given to spare the spinal cord and brainstem per the RTOG guideline.8 Comparatively; the ipsilateral parotids were spared well in the patients treated with VMAT (Table 3). Among all 3 cases, the plan for Patient 1 was the only one that met the mandible constraints recommended by RTOG (Table 3). The remaining two patients did not meet the RTOG constraints for both the maximum and mean dose. Early onset necrosis mainly occurs if the maximum dose is above 70 Gy.10 This was taken in to consideration during the planning processes. The maximum dose for Patient 2 was kept below 70 Gy. However, this was not achieved for Patient 3, whose treatment was planned using SIB IMRT technique. Since more priority was given to the PTVs, the physicians accepted higher dose to the mandible. Clemente et al15 demonstrated that IMRT can spare the larynx better than VMAT. A similar outcome was seen in the three cases (Table 3). There are multiple recommended dose constraints for larynx by RTOG and QUANTEC. None of the patients met the RTOG constraints, which

9 recommended a maximum dose below 45 Gy. The IMRT plan for Patient 3 was the only one that met both the mean and maximum constraints of QUANTEC. The larynx for Patient 2, whose treatment was given using VMAT and 3DCRT, was spared the least. This was due to increased dose contribution from the lateral boost fields. Conclusion All techniques utilized for the three patients, SEQ VMAT, VMAT plus 3DCRT, and SIB IMRT, provided clinically acceptable plans. The ipsilateral parotid was effectively spared for all cases. Patients 2 was re-simulated in between the treatment courses due to weight loss. The initial plan was no longer acceptable because of uncertainties in patient immobilization. The treatment for the remaining fractions was re-planned to account for the change in contour. This technique allowed identifying dosimetric changes and recovering parotid glands sparing. The larynx and mandible presented the greatest challenge. In each case, the PTVs abutted with the mandible and surrounded the larynx. This made it difficult to minimize the dose to these structures while adequately covering the PTVs. Due to the extent of the PTVs, decreasing the maximum dose to the larynx and mandible to less than 66 Gy would compromise the target coverage. The prescribed dose to the tumor, tumor bed or involved lymph nodes was 70 Gy for all patients. Since more priority was given to the PTVs, a maximum dose greater than 66 Gy to the larynx and mandible was accepted. The maximum point dose did not fall within either of these structures for all 3 patients (Table 3). The three cases demonstrated that both VMAT and IMRT have their own specific advantages in oropharyngeal cancer treatments. IMRT has shown to have more advantage in sparing the larynx. On the other hand, VMAT excelled in sparing the mandible and ipsilateral parotid gland. Further studies would be beneficial in evaluating the effectiveness of 3DCRT, IMRT, and VMAT to spare multiple OR of oropharyngeal cancer patients.

10 References 1. Hong AM, Dobbins TA, Lee CS, et al. Human papilloma virus predicts outcome in oropharyngeal cancer in patients treated primarily with surgery or radiation therapy. Br J Canc. 2010;103:1510-1517. http://dx.doi.org/10.1038/sj.bjc.6605944 2. Hong TS, Tome WA, Harari PM. Heterogeneity in head and neck IMRT target design and clinical practice. Radiother Oncol. 2012;103(1):92-98. http://dx.doi.org/10.1016/j.radonc.2012.02.010 3. Bhide SA, Newbold KL, Harrington KJ, et al. Clinical evaluation of intensity-modulated radiotherapy for head and neck cancers. Br J Radiol. 2012;85(1013):487-494. http://dx.doi.org/10.1259/bjr/85942136 4. Eisbrush A, Ship JA, Martel MK, et al. Parotid gland sparing in patients undergoing bilateral head and neck irradiation: techniques and early results. Int J Radiat Oncol Biol Phys. 1996;36(2):469-480. http://dx.doi.org/10.1016/S0360-3016(96)00264-7 5. Blanco AI, Chao C, Naqa IE, et al. Dose volume modeling of salivary functioning patient with head and neck cancer receiving radiotherapy. Int J Radiat Oncol Biol Phys. 2005;62(4):1055-1069. http://dx.doi.org/10.1016/j.ijrobp.2004.12.076 6. Claus F, Duthoy W, Boterberg T, et al. Intensity modulated radiation therapy for oropharyngeal and oral cavity tumors: clinical use and experience. Oral Oncol. 2002;38(6):597-604. http://dx.doi.org/10.1016/S1368-8375(01)00111-7 7. Marks LB, Yorke ED, Jackson A, et al. Use of normal tissue complication probability models in clinic. Int J Radiat Oncol Biol Phys. 2010;76(3):S10-S19. http://dx.doi.org/10.1016/j.ijrobp.2009.07.1754 8. Machtay M. A phase III study of postoperative radiation therapy (IMRT)+/- Cetuximab for locally advanced resected head and neck cancer. Radiation Therapy Oncology Group (RTOG). http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0920. 2013. Accessed August 1, 2013. 9. Verdonck HWD, De Jong JMA, Granzier MEPG, et al. Intensity-modulated radiation therapy for oropharyngeal cancer: Radiation dosage constraint at anterior mandible. Oral Oncol. 2009;45(6):511-514. http://dx.doi.org/10.1016/j.oraloncology.2008.07.007

11 10. Nguyen NP, Vock J, Chi A, et al. Effectiveness of intensity modulated and image guided radiotherapy for spare the mandible from excessive radiation. Oral Oncol. 2012:48(7);653657 http://dx.doi.org/10.1016/j.oraloncology.2012.01.016 11. Ad VB, Lin H, Hwang WT, et al. Larynx-sparing techniques using intensity-modulated radiation therapy for oropharyngeal cancer. Med Dosim. 2012;37(4):383-386. http://dx.doi.org/10.1016/j.meddos.2012.02.004 12. Chen AM, Zahra T, Daly ME, et al. Definitive radiation therapy without chemotherapy for human papillomavirus-positive head and neck cancer. Head Neck. 2013;35(11):1652-1656. http://dx.doi.org/10.1002/hed.23209 13. Ezzell GA, Galvin JM, Low D, et al. Guidance document on delivery, treatment planning, and clinical implementation of IMRT: Report of the IMRT subcommittee of the AAPM radiation therapy committee. Med Phys. 2003;30(8):2089-2115. http://dx.doi.org/10.1118/1.1591194 14. Harrison LB, Sessions RB, Hong WK. Head and Neck Cancer: A Multidisciplinary Approach. 3rd ed. Philadelphia, PA. Lippincott Williams and Wilkins; 2009:331-332. 15. Clemente S, Wu BB, Giuseppe S, et al. Smartarc based volumetric modulated arc therapy for oropharyngeal cancer: a dosimetric comparison with both intensity modulated radiation therapy and helical tomotherapy. Int J Radiat Oncol Biol Phys. 2011;80(4):1248-1255. http://dx.doi.org/10.1016/j.ijrobp.2010.08.007 16. Teoh M, Beveridge S, Wood K, et al. Volumetric-modulated arc therapy (RapidArc) vs. conventional fixed field intensity modulated radiotherapy for F-FDG-PET-guided dose escalation in oropharyngeal cancer: A planning study. Med Dosim. 2013;38(1):18-24. http://dx.doi.org/10.1016/j.meddos.2012.05.002

12 Figures

Figure 1. Patient 1: The sagittal, axial, and coronal views of dose distribution for the cumulative plan. The blue contour represents PTV1, orange contour represents PTV2, and red contour represents PTV3. The Pink isodose line represents 50 Gy, green isodose line represents 64 Gy, and blue isodose line represents 70 Gy.

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Figure 2. Patient 2: The sagittal, axial, and coronal views of dose distribution for the cumulative plan. The brown contour represents PTV1 and red contour represents PTV2. The Pink isodose line represents 50 Gy and blue isodose line represents 70 Gy.

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Figure 3. Patient 3: The sagittal, axial, and coronal views of dose distribution for the cumulative plan. The red contour represents PTV1, green contour represents PTV2, and blue contour represents PTV3. The Pink isodose line represents 50 Gy, purple isodose line represents 64 Gy, and brown isodose line represents 70 Gy.

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Figure 4. Patient 1: DVH of the cumulative plan demonstrating dose distribution to PTV 70, PTV60, PTV54, mandible, larynx, CLAT parotid, and ipsilateral parotid (ILAT Parotid)

Figure 5. Patient 2: DVH of the cumulative plan demonstrating dose distribution to PTV70, PTV50, mandible, larynx, CLAT parotid, and ILAT Parotid

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Figure 6. Patient 3: DVH of the cumulative plan demonstrating dose distribution to PTV 70, PTV63, PTV56, mandible, larynx, CLAT parotid, and ILAT Parotid

17 Tables Table 1. QUANTEC and RTOG dose constraints for parotid glands, mandible, and larynx. Organ Volume Bilateral whole parotid glands Parotid Unilateral whole parotid gland (when sparing both parotids) QUANTEC7 Dmean < 25 Gy RTOG8 20 cc < 20 Gy Dmean < 26 Gy V50 < 30Gy N/A Dmax < 66 Gy Dmean < 38 Gy

Dmean < 20 Gy N/A Dmax < 66 Gy Dmean < 50 Gy [Aspiration] Dmean < 44 Gy [Edema] V50 < 27%

Mandible

Larynx

Whole organ

Dmax < 45 Gy

*Note: Dmean (mean dose), Dmax (maximum dose)

18 Table 2. Prescription and Treatment Planning Parameters Case Site Technique Prescription and Treatment Planning Parameters Patient 1 Patient 2 Patient 3 Tonsil BOT Vallecula VMAT VMAT (SIB) IMRT (SEQ) + (SIB) 3DCRT Standard Standard Standard 6 MV 6 MV 6MV 50 Gy 50 Gy 56 Gy 64 Gy 70 Gy 63 Gy 70 Gy 70 Gy (3) Co-planar arc (3) Co-planar arc beams for PTV1 beams for PTV1 (2) Co-planar arc (2) Co-planar beams (9) Co-planar beams beams for PTV2 and for PTV2 PTV3 PTV1 PTV1 205o 155o coll 5o 235o 105o coll 5o PTV1, PTV2, & 155o 205o coll 355o 105o 235o coll 355o PTV3 o 205o 155o coll 5o 235o 105o coll 5o 160 , 120o, 80o, 40o, 0o, 320o, 280o, 240o, PTV2 PTV2 200o 210o -179o coll 10o 270o and 90o 179o - 210o coll 350o PTV3 210 - 150o coll 20o 150o - 210o coll 340o
o

Fractionation Beam Energy Dose to PTV1 Dose to PTV2 Dose to PTV3 Beam Arrangement

Gantry Angles/ Rotations

*Note: BOT (base of tongue), MV (megavoltage), SIB (simultaneous integrated boost), coll (collimator)

19 Table 3. Plan Analysis and Evaluation Plan Analysis and Evaluation Structures PTV1 PTV2 PTV3 Ipsilateral parotid Mandible Larynx Brain stem Spinal cord Oral cavity Patient 1 (Gy) Dmean Dmax 51 55 65.3 71.4 16.4 38.4 51 4.4 26.3 37.8 69.8 76.3 63 65 67.8 31.5 35.3 52 Patient 2 (Gy) Dmean Dmax 49 52.2 69.7 N/A 19.6 40.3 69.4 13.5 22.7 37.2 73.7 N/A 70.4 69.3 72.9 40 38.5 53 Patient 3 (Gy) Dmean Dmax 63.4 76.2 70.1 72.7 20.0 45.4 41.4 17.9 21.8 36.2 76.2 76.2 58.6 74.6 53.5 44.8 42.3 69.5

*Note: the Dmean and Dmax shown here represent the result of the composite plan