KAYLA TEDRICK



An evaluation of the dosimetric impact of weight loss throughout the course of radiotherapy in bilateral head and neck cancer patients: determining treatment re-planning guidelines for both VMAT and IMRT delivery techniquesIntroductionIn the group of cancers of the head and neck, most are commonly squamous cell carcinomas and can be associated with risk factors such as tobacco and alcohol use.1 Head and neck cancers are common, with the incidence being twice as high in males as in females. In total, there will be an estimated 51,540 new cases of oral cavity and pharyngeal cancer in the United States in 2018.2 For cancers of the oral cavity and pharynx, the 5-year survival rate is 65%. For cancer of the head and neck, standard treatments often include radiation therapy and surgery, in combination or separate, with chemotherapy being utilized for specific use-cases. The radiation treatment of head and neck cancer has progressed dramatically over the past several years. Technological advancements, such as the utilization of contrast-enhanced diagnostic-quality computed tomography (CT) during radiation treatment planning, has significantly contributed to this improvement. Likewise, the use of Intensity Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) treatment planning and delivery have become commonplace in the external beam treatment of head and neck disease.1 These treatment techniques have led to dose escalation and reduction of the associated toxicity for many head and neck patients. Despite these advancements, head and neck radiation therapy still often results in significant side effects, such as mucositis and dysphagia, for many patients throughout the course of treatment. Due to the toxicities that commonly frequent head and neck patients under treatment, patient health is monitored closely throughout the course. Weight loss is a common occurrence in this patient group due to the associated side effects. Specifically, dysphagia and mucositis can often make it difficult for patients to maintain the proper intake without assistance or intervention.3 Based on this increased propensity for weight loss during treatment, awareness of the volumetric and anatomic changes that may occur as a result have opened discussion on how the dosimetric distribution may be affected to both the target areas and surrounding normal tissues. There are many normal structures in the head and neck area that are critical to avoid during radiation treatment planning in order to maintain proper function. However, weight loss has been found to cause the planned dose in normal structures to deviate. This is also the case for the dose distribution to the defined target volumes.4 Due to these findings, re-planning of patients who have experienced weight loss during treatment has become increasingly common. Castelli et al5?concluded that patients with a change in anatomy during treatment received an overdose of more than 2.5?Gy?to the parotid glands and that weekly re-planning reduced the parotid gland mean dose by 4?Gy.?Similarly, a study by Zhao et al6 found an increase in the dose to 1% (D1) of the spinal cord and brainstem volumes of 5.6 Gy and 2.5 Gy, respectively. As for target volumes, changes in dose distribution have been found to be more negligible due to the use of a planning target volume (PTV) that provides margin for error.4 Despite these dosimetric findings, the possibility exists that re-planning is not always required and practical. Hunter et al7 concluded that re-planning is unlikely to improve salivary output after treatment in most cases, even though re-planning can reduce the mean dose to the parotids. Additionally, there has been no definitive method established to define the amount of weight loss in the head and neck region that necessitates a re-plan. El-Sayed et al8 claimed that patients should be re-simulated and re-planned if more than 10% of the weight loss occurs within the first three weeks of radiation treatment. However, patients chosen to be re-planned in the El-Sayed study were selected based upon inadequate setup for daily treatment rather than specifically weight loss alone. The incorporation of setup-related error introduces alternate dosimetric variables into consideration. As a result, a true recommendation on when to initiate re-planning based on true anatomic loss remains arbitrary.The objective of this retrospective study was to assess the dosimetric effects of weight loss in head and neck patients who were defined as having “acceptable daily positioning,” which was quantified based on anatomic landmarks. These patients were all planned with VMAT and IMRT treatment techniques and the resulting deviations in dose distribution were evaluated. From this dosimetric data, the need for re-planning could be assessed. Given the many resources required for re-planning and potential for treatment breaks, the possibility exists that re-planning may not always be the best treatment option for patients with mild weight loss based on the significance of dosimetric changes. An investigation into these results could provide useful steps in determining when re-planning becomes necessary due to weight loss alone, ultimately allowing for the establishment of weight loss parameters and re-simulation guidelines. Additionally, this study assessed the dosimetry impact of weight loss for both VMAT and IMRT techniques to determine if there is a difference in plan robustness between the delivery methods as a patient loses mass. Methods and MaterialsPatient SelectionData was collected from 22 head and neck cancer patients diagnosed with a primary cancer of the head and neck area. Based on diagnosis, each was treated bilaterally to the lymph node levels of the neck, including bilateral supraclavicular nodal involvement. Head and neck patients with disease of the nasopharynx were excluded from this study. Each patient was simulated in a supine position on a GE Discovery CT scanner with a setting of 2.5 mm slice thickness. A conformal head and neck board was used for each patient. Immobilization included either a Q-fix “Q2” with a custom headrest or a Silverman “C” headrest with two 1 millimeter shims placed underneath. Long thermoplastic masks were formed for each patient with shoulders placed inferiorly with arms at sides. This was accomplished by having the patients grasp indexed pegs placed into the lateral aspect of the conformal head and neck board (Figure 1). Some patients were simulated with custom mouthpieces to immobilize the maxilla per physician’s request. A knee sponge was placed underneath the legs for comfort.In the patient population, each experienced weight loss in the head and neck area throughout the course of treatment as identified by the attending physician and treatment team on daily imaging. To evaluate whether the weight loss was resulting in loss of target coverage or increased dose to organs at risk (OAR), patients received an assessment CT positioned in standard treatment setup at the request of an attending physician. In order to narrow the focus to weight loss and eliminate other dosimetric variables involving the setup, patients were only selected for this study if they were defined as having “acceptable daily positioning” based on the registration between the original CT and the assessment CT. Specifically, “acceptable daily positioning” was defined as having no translational shift greater than 0.6 centimeters, concentrating on the spinal column from C1 and extending to the vertebral body representing the most inferior in-field region of the supraclavicular target volume. The translational shifts included the left to right, anterior to posterior, and superior to inferior directions, which were each assessed independently.ContouringFollowing simulation, the patient’s CT dataset was imported into the Eclipse treatment planning system (TPS). Organs at Risk (OAR) were contoured by a certified medical dosimetrist per Radiation Therapy Oncology Group (RTOG) 1016 with few noted exceptions. For the purposes of this study, the exceptions included the segmentation of the esophagus, larynx, and pharynx structures. Specifically, the esophagus was contoured from the distal end of the pharynx to 1 centimeter below the inferior portion of the PTV to include all in-field contents. The larynx was contoured to include suprahyoid epiglottis superiorly and extend inferiorly to the level of the cricoid cartilage. The larynx contour extended from the anterior commissure to include the arytenoids, and the infra-hyoid region was segmented as a triangular prism shape. The pharynx included the posterior pharyngeal wall from the base of the skull to the cricoid cartilage, including adjacent constrictor muscles. No OAR were cropped or subtracted from target volumes for the dose evaluation portion of this study. Immobilization contents, such as the posterior mask and head rest, were contoured when appropriate such that attenuation would be included in the dose calculation. The normal tissue contours were reviewed by attending physicians, and ten specific OAR were selected to be evaluated on both the original CT and assessment CT for dosimetric evaluation in this study. This evaluation criteria included: spinal cord, spinal cord planning risk volume (PRV), brainstem, brainstem PRV, oral cavity, parotid glands, pharynx, larynx, and esophagus. For consistency of evaluation, nomenclature was templated as _R_SpinalCord, _R_SpinalCord_05, _R_Brainstem, _R_Brainstem_03, _R_Esophagus, _R_Layrnx, _R_Pharynx, _R_Cavity_Oral, _R_Parotid_L, and _R_Parotid_R corresponding to each associated OAR.All target volumes were then contoured by attending physicians. The gross tumor volume (GTV) and clinical target volumes (CTV) were initially contoured based on the registration between the contrast-enhanced planning CT and a diagnostic PET/CT. Segmentation of the GTV was defined to include the primary tumor and clinically positive lymph nodes seen either on the planning CT or pre-treatment PET imaging with a standardized uptake value (SUV) greater than 3 g/mL. The CTV was defined to include appropriate lymph node levels based on risk-assessment by attending physicians, as well as a standard uniform margin of 5 millimeters applied to GTV delineations where appropriate. Multiple CTVs were created and separated into a high risk volume, intermediate risk volume, and low risk volume corresponding to the prescribed dose to each, the high risk volume being prescribed the highest dose. To establish segmentation consistency, the low risk volume included both the intermediate risk volume and the high risk volume in addition to the low risk volume (Figure 3). Likewise, the intermediate risk volume contained the high risk volume in addition to the intermediate. The planning target volumes (PTV) were separated in the same manner as CTVs and were created by uniform expansion of the CTVs 3-5 millimeters in all directions based on imaging frequency. Per physician, the PTV and CTV volumes were permitted to be extracted 0.3 centimeters from the external contour of the patient surface to exclude the dermis and epidermis layers of the skin. For the evaluation purpose of this study, duplicate targets contours were created and labeled _R_PTV_High, _R_PTV_Int, _R_PTV_Low, _R_CTV_High, _R_CTV_Int, and _R_CTV_Low corresponding to the originally defined risk levels and target types (Figure 2).For segmentation of the assessment CT, the ten identified OAR were delineated in the same defined manner as employed during original creation. This also included the same contouring exceptions to the R_Larynx, R_Pharynx, and R_Esophagus contours as previously annotated. In addition to OAR, the original target volumes were transferred from the original CT to the assessment CT and extracted 3 millimeters from the patient’s external surface to account for skin build-up. Normal structure contours and target volumes were edited as needed and physician-approved. This included adjustments to R_CTV and R_PTV structures where applicable. Support structures—including immobilization—and external surface were also re-contoured on the assessment CT to include in dose calculation. Treatment PlanningThe treatment plans on the original planning CTs were all planned with a VMAT method in the Eclipse TPS and physician approved. With every patient dataset including 2-3 PTVs, the plans all involved the utilization of a simultaneous integrated boost (SIB) technique. To extend the scope of this study, as well as to compare the robustness of different planning techniques, a 9-field IMRT plan using a dynamic MLC sliding window method was created on the original planning CT of each patient and physician approved. The patients selected were prescribed definitive doses by attending physicians. Of the 22 patients, 20 were prescribed 70 Gray (Gy) in 35 fractions to the PTV_High, 63 Gy to the R_PTV_Int, and 56 Gy to the R_PTV_Low to be delivered simultaneously. The remaining two patients were prescribed a dose regimen of 69.96 Gy in 33 fractions to the PTV_High, 59.4 Gy to the R_PTV_Int, and 54.12 Gy to the R_PTV_Low to be delivered simultaneously. Due to the bilateral involvement of disease in each patient, the arc angles chosen for the VMAT plans were all a variation of a full arc. Each treatment plan involved at least three arcs but no more than four and 6 MV was the designated energy (Figure 3). The collimator angles and sizes chosen for each arc were selected to maximize the efficiency of the multi leaf collimators (MLCs) in blocking out OAR along with achieving an adequate dose conformity. For IMRT treatment planning, 9 fields were arranged equidistant around the patient with 6 MV energy selection. Collimation of 90 degrees was chosen for gantry selections of 200, 0 and 160 degrees to allow for efficient MLC blocking of midline structures. The other 6 beams employed a 0 degree collimator setting. The MLC delivery method for the IMRT technique was dynamic sliding window. All treatment plans were executed on Varian Truebeam linear accelerators.The planning constraints used were established from suggestions stated in the RTOG 1016 protocol (Figure 8) along with departmental objectives. All plans on the original CT datasets were normalized to ensure that 100% of each prescription dose covered 95% of each of the individual PTVs. The maximum dose, defined as dose to 0.03cc, was not to exceed 110% of the prescription dose with an acceptable variation of 115%.Each VMAT plan was optimized in either the progressive resolution optimizer (PRO) version 13.6.23 or the photon optimizer (PO) version 13.6.23. Similarly, IMRT plans were optimized in PO version 13.6.23 of Eclipse. All plans were calculated with the Acuros External Beam (AcurosXB) version 13.6.23.Quantification of Weight LossThe primary focus of this study was to examine the variation in dose distribution for patients that experience weight loss in the head and neck area during their course of radiation therapy. In order to do so, it was required that weight loss be quantified in geometric measurements such that they could be replicated with treatment imaging. As a result, weight loss was defined as the measured difference in separation between the original planning CT and the assessment CT at various landmarks. Separations were measured by reviewing three diameters at three vertebral levels in the head and neck: C1, C3, and the interspace of C4/C5. To collect these measurements, viewing planes were positioned at midline of the vertebral body in the sagittal and coronal planes and positioned at the most anterior apex of the vertebral body in the axial plane (Figure 4 and 5). On the viewing plane axis for each vertebral level, three vectors were placed to measure separation. The first two vectors were drawn diagonally, 60 degrees apart from the central axis bifurcating the anterior apex of the vertebral body (Figure 5). These vectors were chosen to ensure that the difference in diameter measured from the original CT to the assessment CT was representative of the total circumferential loss in the head and neck area. The third vector was drawn by bifurcating the anterior apex of the vertebral body extending left to right along the horizontal axis (Figure 6). This process was repeated at all three vertebral levels for both the original CT and the assessment CT, measuring to the external contour of the patient habitus (Figure 7). The measured difference between corresponding vectors of the original and assessment CT were then recorded for all 9 vectors, and averaged as a quantifiable metric of weight loss for the head and neck region. Likewise, the maximum vector difference was recorded for the 9 vectors on each patient to establish magnitude of weight loss. Plan ComparisonsTo assess the effects of the patients’ weight loss on the dose distribution, a verification plan of the original VMAT and 9-field IMRT plans were calculated on the assessment CT using all original plan parameters. This was done by forming a rigid registration in Eclipse (TPS) between the original planning CT and the assessment CT for each patient. In the same manner as defined in patient selection, qualifiers of “acceptable daily positioning” were applied. This consisted of an imaging review to ensure that the rigid registration did not include a translational shift greater than 0.6 centimeters, concentrating on the spinal column from C1 and extending to the vertebral body representing the most inferior in-field region of the PTV. Each vertebral body was independently analyzed to ensure that all criteria were satisfied. Following review, the translational shifts from the rigid registration were then applied to the verification plan performed on the assessment CT prior to calculation. Shift application was performed to mimic the methodology associated with daily imaging and treatment on the linear accelerator.Following the calculation of the verification plans on the assessment CTs, coverage to the target volumes and dose to OAR included in the structure set were recorded and compared to the original treatment plan. The metrics evaluated were chosen with reference to RTOG 1016. They included the dose to 95% of the target [D95] and dose to 5% of the target [D5] for PTVs, dose to 95% of the target [D98] for CTVs, dose to 99% of the _R_GTV_High [D99], maximum dose to _R_SpinalCord, _R_SpinalCord_05, _R_Brainstem, _R_Brainstem_03, mean dose for the parotid glands, _R_Larynx, and _R_Esophagus, mean dose and percent volume receiving 65Gy [V65] for _R_Pharynx, and lastly mean and maximum dose for the _R_Cavity_Oral (Table 1). The percent difference between the metrics on the original plan CTs and the metrics on the verification plans were then calculated. This was completed for both the VMAT and 9 field IMRT plans. ResultsDiscussionConclusionReferencesArgiria A, Karamouzis MV, Raben D, Ferris RL. Head and neck cancer. Lancet. 2008;371(9625):17-23. (08)60728-XAmerican Cancer Society. Cancer facts & figures 2018. . Revised June 2018. Accessed July 26, 2018.Dawson P, Taylor A, Bragg C. Exploration of risk factors for weight loss in head and neck cancer patients. J Radiother Pract. 2015;14(4):343-352. CL, Steenbakkers RJHM, Langendijk JA, Sijtsema NM. Identifying patients who may benefit from adaptive radiotherapy: Does the literature on anatomic and dosimetric changes in head and neck organs at risk during radiotherapy provide information to help? Radiother Oncol. 2015;115(3):285-294. Castelli J, Simon A, Rigaud B, et al. A nomogram to predict parotid gland overdose in head and neck IMRT.?Radiat?Oncol. 2016;11(79):1-11.? L, Wan Q, Zhou Y, Deng X, Xie C, Wu S. The role of replanning in fractionated intensity modulated radiotherapy for nasopharyngeal carcinoma. Radiother Oncol. 2011;99(2):23-27. K, Fernandes L, Vineberg K, et al. Parotid glands dose–effect relationships based on their actually delivered doses: implications for adaptive replanning in radiation therapy of head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2013;87(4):676-682. S, Yemchuk S, Broomfield J, Bahn J. Is percentage of weight loss predictive of the need for re-planning of patients with head and neck cancer treated with IMRT radiotherapy? Results of a prospective study. Int J Radiat Onc Biol Phys. 2011;81(2):S540-S541. 1. Example of patient setup lying supine on the conformal head and neck board with an aquaplast mask formed to head and neck area, hands holding onto pegs, and knee sponge for comfort.Figure 2. Example of a high risk volume in red (_R_PTV_High), intermediate risk volume in blue (_R_PTV_Int), and low risk volume in green (_R_PTV_Low).1228725990600012192001190625033623259906010Figure 3. Example of a 4 arc VMAT treatment plan summary.Figure 4. Example of where the viewing planes are placed for a C1 measurement.Figure 5. Example of where the viewing planes are positioned for C1 measurement as well as where the two diagonal vectors are drawn.Figure 6. Example of the three measurements taken at C1.Figure 7. Example of the assessment CT overlaying the original CT with both external contours demonstrating change in tissue. Figure 8. Table showing the dose objectives used when planning the original VMAT and IMRT plans.TablesTable 1. Table showing the metrics evaluated to compare the original plans to the verification plans. ................
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