1 Ashley Pyfferoen Semester Case Study November 20, 2013 Brachial Plexus Dose Limitations in Apical Lung Cancer

Abstract: Introduction: This study aims to evaluate the dose limitations of the brachial plexus for apical lung cancer patients and how dose prescription is compromised to accommodate for the dose limitations. Case Description: In the treatment of apical lung cancer, the ipsilateral brachial plexus is frequently involved in the cancer invasion or incorporated in the treatment fields. The maximum allowable dose to the brachial plexus often compromises the prescription dose in a variety of treatment regimens and is demonstrated in the following 5 case studies: Patient 1 represents Intensity Modulated Radiation Therapy (IMRT) treatment of diffuse small cell lung cancer in the left lung apex with brachial plexus, mediastinal and supraclavicular nodal involvement; Patient 2 represents IMRT of the right lung apex for the treatment of non-small cell lung cancer (NSCLC) with brachial plexus involvement, Patient 3 represents a case of IMRT to treat NSCLC of the right lung apex with significant mediastinal and brachial plexus invasion, Patient 4 represents treatment of NSCLC in the left lung apex using IMRT and Patient 5 represents a case of IMRT for the treatment of small cell lung cancer in the right lung apex with brachial plexus involvement. Conclusion: Each plan was evaluated based on the effectiveness of limiting dose to the brachial plexus vessels and spinal cord. The restrictions on the brachial plexus were heavily dependent upon the physician and prescription dose. The dose volume histogram (DVH) was used for plan evaluation and provided a quantitative analysis regarding the maximum dose to the brachial plexus and the amount of tumor volume receiving 100% of prescription dose. While the goal of treatment was to respect the brachial plexus limitation, the prescription dose was compromised to achieve the desired objectives. Key Words: Brachial Plexus, Radiation Induced Brachial Plexopathy (RIBP), IMRT

2 Introduction The brachial plexus is defined as a complex collection of nerves that are responsible for operating the motor and sensory functions of the wrist, hand, elbow and shoulder. These nerves originate from ventral rami of cervical nerves 5-8 (C5-C8) and thoracic nerve 1 (T1) and travel parallel to the subclavian artery through the supraclavicular fossa.1 The brachial plexus forms 3 trunks while traveling distally and separates further to form 6 divisions near the clavical.1 The final division (3 cords) of the brachial plexus occurs at the lateral border of the pectoralis minor muscle and make up the axilla.1 The brachial plexus is a significantly sensitive structure to injury especially in the field of radiation oncology. If care is not taken to preserve the brachial plexus while treating cancer patients in the axilla, significant and debilitating damage can occur. Radiation induced brachial plexopathy is the damage of nerves in the brachial plexus when treated with high doses of radiation. The side effects of RIBP are incapacitating and include pain and weakness in the arm, shoulder and hand; paresthesias and even paralysis in the most extreme cases.2 Radiation induced brachial plexopathy can severely affect the quality of life of a patient and the damage is irreversible, therefore, treating the brachial plexus to below dose limitations is required. However, discrepancies between the dose limitations of the brachial plexus exist indefinitely and vary depending on the literature. Significant literature has proposed dose limitations of the brachial plexus in head and neck cancer and breast cancer patients, however, few articles have outlined brachial plexus neuropathy in apical lung cancer patients.3,4,5,6 The most respected literature outlines 60-66 Gray (Gy) as the dose constraint for the brachial plexus.7 In the case of apical lung cancer, the dose regimens often exceed this dose constraint and physicians are faced with the difficulty of preserving the brachial plexus while curatively treating invasive cells. In most cases, the solution occurs at the expense of prescription dose and tumor coverage. All 5 cases presented were evaluated based upon apical lung involvement and brachial plexus invasion. Furthermore, each patient was treated by 1 of 3 physicians and with a distinctive dose prescription. All 5 cases were considered acceptable based upon maximum doses to the brachial plexus and superior spinal cord. Prescription dose coverage was also a determining factor in plan

3 viability and was evaluated based upon the maximum dose, mean dose and percentage of tumor coverage. Methods and Materials Patient Selection Each of the cases presented with specific similarities. All 5 patients chosen were diagnosed with apical lung cancer of either lung with distinct brachial plexus involvement. Patient 1, a 50 yearold male, presented with a diagnosis of Stage IV small-cell carcinoma of the left lung apex extending superiorly to the brachial plexus and medially to the mediastinal and supraclavicular nodal regions. Several lung nodules were identified extending from the superior lobe to the inferior lobe of the left lung. While the lung nodules extensively involved the entire organ, only the 2 most superior nodules were delineated as Planning Target Volumes (PTVs) for the focus of treatment. Treatment intent was carefully considered, however, due to the dispersion of lung nodules and nodal and brachial plexus involvement; local control was the goal of treatment. The objective of local control was to successfully control gross disease and prevent metastatic spread to further sites. To achieve this goal, the radiation oncologist elected to treat with a lower prescription dose. While the dose was lower, there was concern for critical structure dose limitations due to the PTV-brachial plexus overlap. This case demonstrated the proximity and dose restrictions of the brachial plexus and how treatment planning was modified to avoid these doses. Patient 2, a 74 year-old female, presented with Stage IV, T4 (Stage 4 primary tumor), N0 (Stage 0 regional lymph nodes), M0 (Stage 0 metastatic disease) NSCLC, specifically squamous cell carcinoma of the right lung apex. The lesion was negative for mediastinal involvement but positive for chest wall and brachial plexus invasion. In this case, 1 PTV was delineated for the focus of treatment and was treated curatively. While the tumor size was considerable, evidence of nodal or metastatic involvement was nonexistent and local control was agreeable. The treatment planning regimen administered high doses of radiation to the delineated PTV for curative intent. However, due to the proximity and overlap between the PTV and brachial plexus, the treatment volume dose was modified in the superior aspect of the PTV to account for these dose limitations.

4 Patient 3 is a 54 year-old male who presented with T4, N2 (Stage 2 regional lymph nodes), MX (metastasis could not be evaluated) NSCLC of the right lung apex with mediastinal and brachial plexus involvement. One PTV was delineated for the purpose of treatment and encompassed the gross disease with moderate margins. The goal of this treatment regimen was local control. The tumor size and nodal involvement was indicative of incurable NSCLC and a moderate target dose was prescribed with special accommodations for the brachial plexus intersection. Patient 4, a 66 year-old female, presented with Stage IIIB-4 NSCLC of the left lung apex with considerable mediastinal and supraclavicular adenopathy. The physician delineated 1 PTV to encompass visible gross disease, involved lymph nodes and moderate margins. Due to the magnitude of disease, the patient was treated using a local control treatment regimen. Despite a lower total dose, there was still substantial concern for brachial plexus overdose, therefore, the tumor dose was compromised in areas overlapping or adjacent to the brachial plexus. Patient 5 is a 74 year-old male who presented with T2 (Stage 2 primary tumor), N0, M0 small cell lung cancer of the right lung apex with brachial plexus extension. One PTV was delineated the included 2 separate gross disease sites. Adequate margins were added to the sites to ensure complete inclusion of all microscopic disease. Considering the limited extent of the disease, the patient was given a higher dose for curative intent. However, the brachial plexus and tumor overlap provided significant limitations for dose coverage in the superior aspect of the PTV. Patient Set-up The set-up technique for each patient simulation was dependent upon superior tumor parameters and differed slightly between physicians. Based upon standard protocol, each patient was placed in the supine position, head first into the General Electric (GE) Computed Tomography (CT) scanner. Patient 1 was securely immobilized using a pliable head and neck Orfit mask. The mask was molded directly to the patients contour and secured to the table to immobilize the chest cavity. Patients 2-5 were placed in a Vac-lok immobilization device and secured to a wing board to remove the patients arms from the treatment fields. In each case, an appropriate head and neck rest was secured to the table for patient comfort. To aid in patient set-up consistency, radiopaque reference markers were placed anteriorly and laterally (left and right) on the patients

5 skin to define a reference point for treatment planning. Exac-Trac imaging was used to aid in daily reproducibility for every patient. Target Delineation Target delineation was specified using the Philips Pinnacle3 8.0 treatment planning system (TPS) or the Varian Eclipse Version 10.0 TPS. For Patient 1, the CT scan obtained during simulation was uploaded to the Pinnacle3 8.0 TPS. The radiation oncologist successfully delineated the gross tumor volumes (GTV) for each lesion using Positron Emission Tomography (PET) and CT imaging. To successfully encompass the delineated lesions and microscopic disease, each GTV was given a 3 millimeter (mm) expansion and labeled as the PTV. The upper lung nodule and mid-lung nodule were regarded as PTVUpLungNodule and PTVMidLungNodule, respectively. Critical structures at risk included the brachial plexus, left lung, right lung, heart, spinal cord, larynx and esophagus. The CT scan obtained from Patient 2 was uploaded to the Varian Eclipse Version 10.0 TPS for dosimetric planning. A PET scan was used to aid the radiation oncologist in GTV delineation on the planning CT. Furthermore, the physician expanded the GTV volume 3 mm to encompass gross and microscopic disease and denoted the structure as the PTV. Structures at risk during treatment included the brachial plexus, left lung, right lung, heart, spinal cord and esophagus. For Patient 3, the CT scan was uploaded to the Pinnacle3 8.0 TPS. The radiation oncologist precisely identified the GTV with the aid of a PET scan. An Internal Target Volume (ITV) was established as an expansion of the GTV volume to account for internal organ movement. Using the ITV, the radiation oncologist supplied sufficient margin to the ITV to create the PTV for optimization and dosimetric calculations. Critical structures indicated for this patient included the brachial plexus, left lung, right lung, heart, spinal cord, and esophagus. A CT scan of Patient 4 was uploaded to the Pinnacle3 8.0 TPS. A recent PET scan was fused with the planning CT images to create a precise area for treatment and GTV delineation. An ITV was created from the GTV volume to account for internal organ movement and a PTV was defined from the ITV and included adequate margins to encompass microscopic disease. Structures at risk included the brachial plexus, total lung, spinal cord, esophagus and heart.

6 For Patient 5, the CT scan was uploaded to the Pinnacle3 8.0 TPS. The CT images were fused with a PET/CT scan to assist in delineation of gross disease. The GTV was delineated using the fused image set and a PTV was created by adding sufficient margin to the GTV and accounted for microscopic disease and dosimetric calculations. Treatment Planning The dose prescription and beam angle arrangements are demonstrated accordingly in Table 1 and 2 for all patients. Patient 1 was given an adequate prescription dose of 61.2 Gy in 34 fractions (fxs) to achieve local control of both lesions. To achieve the best conformity, the radiation oncologist requested that IMRT be used to treat the lesions and that 100% of the prescription dose cover 95% of the PTV targets. However, the significant brachial plexus and spinal cord invasion provided difficulty in attaining the dose homogeneously throughout the PTVs (Figure 1). To accommodate for the dose limitations, appropriate margins were given to the brachial plexus and spinal cord contours. A 3 mm margin was given to each structure for optimization and to account for patient set-up and immobilization errors. The radiation oncologist elected the expanded brachial plexus and expanded spinal cord to receive maximum doses of 63 Gy to .03 cubic centimeters (cc) of volume and 50 Gy, respectively. In addition, the right and left lungs could not receive 50 Gy (V50) to more than 60% of the volume and not more than 20 Gy (V20) to 30% of the volume. The mean dose to the esophagus could not exceed 40 Gy and not more than 25% of the esophagus could receive a dose of 60 Gy (V60). The heart was listed with 2 constraints including V60 33% and the volume receiving 45 Gy (V45) was to be less than 67%. Finally, the larynx could not exceed a mean dose of 40 Gy. The optimization parameters in IMRT planning were used to achieve these objectives and a suitable plan was generated.

Patient 2 was prescribed a higher dose for curative intent at 66 Gy for 33 fxs. The radiation oncologist instructed the use of IMRT to obtain an appropriate plan and that 100% of the prescription dose cover 95% of the PTV as per department protocol. However, due to the significant brachial plexus and PTV overlap, insufficient dose distribution around those areas was acceptable (Figure 2). To ensure the brachial plexus would not be overdosed, the contour was expanded 2 mm. Furthermore, the proximity of the spinal cord was also a concern thus the spinal cord contour was expanded 5 mm for margin and error. The radiation oncologist elected

7 that the brachial plexus and spinal cord did not receive maximum point doses of more than 60 Gy and 45 Gy respectively. The left and right lung were given the constraint of V20 30% and the esophagus could not exceed a mean dose of 32 Gy. The parameters were set for IMRT optimization to create a suitable plan for the patient. Local control of the disease was the objective for treatment of Patient 3. The patient was prescribed to 60 Gy in 30 fxs using the treatment technique of IMRT. Similar to Patient 1 and 2, the apical tumor significantly invaded the brachial plexus and created several treatment difficulties (Figure 3). The radiation oncologist disregarded typical department practices for PTV coverage and instructed that attaining the best dose distribution while meeting the given constraints was acceptable. For optimization, the brachial plexus was expanded 2 mm and the spinal cord was expanded 5 mm. The radiation oncologist instructed maximum doses of 60 Gy and 45 Gy to the expanded brachial plexus and expanded spinal cord, respectively. Other constraints listed included left and right lung V20 25% and the volume receiving 5 Gy (V5) was to be less than 55%. The mean dose for the total lung volume could not exceed 17.5 Gy. Finally, the heart and esophagus constraints were listed at mean doses less than 30 Gy and 25 Gy respectively. A suitable plan was generated using the stated objectives, inverse planning and conscientious beam optimization. Due to the extent of disease, Patient 4 was treated using a local control prescription at 60 Gy in 30 fxs. The radiation oncologist instructed the use of IMRT for the radiation treatment and set objectives for PTV dose requirements. While department protocol indicates that 100% of the prescription dose covers 95% of the PTV, the physician indicated that would not be possible in this case due to the severity of brachial plexus overlap (Figure 4). He noted to achieve prescription dose to the inferior aspects of the PTV and specified that 57 Gy must encompass 95% of the delineated PTV entirely. For optimization and marginal purposes, the brachial plexus was expanded 2 mm and the spinal cord was expanded 5 mm. The brachial plexus and spinal cord were given maximum limiting doses of 60 Gy and 44 Gy, respectively. The left and right lung contours were combined to create a total lung contour and given objectives of V20 30%, V5 60% and a mean lung dose of less than 18 Gy. Finally, the esophagus and heart mean doses could not exceed 25 Gy and 30 Gy respectively. These parameters were set for IMRT optimization and appropriate plan generation.

8 Patient 5 was diagnosed with limited disease and was treated for curative intent with a prescription of 66 Gy in 33 fxs. The proximity of dose limiting structures prompted the use of IMRT for plan generation. The physician listed the conventional department protocol PTV objective of 100% of prescription dose to 95% of the tumor for this particular patient. He also noted that if this objective was not attainable due to the brachial plexus overlap, he would accept 60 Gy to 95% of the PTV as an alternate (Figure 5). The brachial plexus and spinal cord were expanded 2 mm and 5 mm for dose-limiting margin. The physician instructed the brachial plexus and spinal cord to receive doses less than 60 Gy and 45 Gy, respectively. The left and right lungs were confined to V20 35% and a mean dose of less than 20 Gy. The heart was given numerous constraints of V60 33%, V45 65% and the volume receiving 40 Gy (V40) was to be less than 100%. The final constraint was listed for a mean esophageal dose of less than 34 Gy. The medical dosimetrist approached each of the cases analogously and established dose objectives for the critical structures and PTV simultaneously before initial optimization. In order of importance for Patient 1, the expanded spinal cord and expanded brachial plexus were given appropriate objectives to satisfy the requirements of the radiation oncologist. Secondly, 2 objectives for each PTV were established, a minimum dose of 61.2 Gy and a maximum dose of 61.2 Gy. Subsequently, the esophagus, heart, larynx and total lungs objectives were set and listed at lower priority accordingly. The plan optimization for Patient 2 utilized different target volumes to meet the constraints issued for the PTV and brachial plexus. The PTV that overlapped the expanded brachial plexus was given a maximum objective of 60 Gy, the area in close proximity to the brachial plexus was given a minimum objective of 63 Gy and a maximum objective of 65 Gy, and the area distal to the brachial plexus was given minimum and maximum objectives of 66 Gy. The expanded brachial plexus and expanded spinal cord were given maximum objectives and set at the highest priority. The total lung and esophagus objectives followed and were prioritized accordingly. A base dose plan was created to account for tissue inhomogeneities at the lung interface and was utilized as a starting point for the final optimization. The PTV objectives for Patient 3 were dependent upon brachial plexus overlap. The PTV that overlapped the expanded brachial plexus was given a maximum dose objective of 57.5 Gy and a

9 minimum dose objective of 57 Gy. The outstanding PTV was given a maximum dose objective of 62 Gy and a minimum dose objective of 58.8 Gy. The expanded brachial plexus and expanded spinal cord were given appropriate constraints and prioritized appropriately. The total lung contour and esophagus were also given objectives and given lower priority. Similar to Patient 3, the PTV objectives for Patient 4 were dependent upon the tumor volume and brachial plexus overlap. The portions of PTV that overlapped with the brachial plexus were given a maximum dose of 57.5 Gy and a minimum dose of 57 Gy to achieve dose constraints. The distal PTV was given appropriate prescription objectives. The distal PTV was given a maximum objective of 60 Gy and a minimum objective of 58 Gy. The brachial plexus and spinal cord were among the highest priority objectives and were set accordingly in the optimizer. The total lung contour, heart and esophagus were given appropriate objectives and prioritized accordingly. The objectives for Patient 5 were strategically created by subtracting dose limiting structures from the treatment volume. The target volume that overlapped with the brachial plexus was subtracted to create a separate volume for optimization. This volume was given a maximum dose objective of 60 Gy and a minimum dose objective of 58 Gy to ensure a maximum dose of less than 60 Gy. The subsequent PTV was given dose objectives that more closely match with prescription requirements. This volume was given a maximum dose objective of 67 Gy and a minimum dose objective of 64.5 Gy. The brachial plexus and spinal cord were given objectives in the optimizer and were set at higher precedence. The lung, esophagus and heart objectives were also incorporated and given a lower priority. Each plan was optimized heterogeneously to account for density variances at the lung-tissue interface. In each case, dose limitation to the brachial plexus and spinal cord were crucial. Therefore, the simultaneous optimization of the PTV, brachial plexus and spinal cord was necessary to ensure each of the constraints were met. Plan Analysis & Evaluation In each case the dose limitations to the brachial plexus and spinal cord were inflexible. Therefore, the treatment technique of IMRT was essential in the optimization of each treatment plan and achieving the most important patient goals. Intensity modulated radiation therapy is known for the ability to deliver high doses of radiation to target volumes while sculpting around

10 critical dose-limiting structures with precision and accuracy.8 With this in mind, the plans were evaluated accordingly. The medical dosimetrist successfully attained the dose constraints and created an optimal dose distribution for plan given to Patient 1. The plan successfully delivered 100% of the prescription dose to 95% of the delineated PTVs after normalizing to the 98.9% isodose curve (Figure 6 and 7). The maximum dose to the brachial plexus was observed at 63.05 Gy to 0.03 cc and spinal cord maximum dose was 49.78 Gy. The V60 for the total lung volume was 8% and the V20 was 28%. The esophagus mean dose was 26.15 Gy and V60 was 2%. The V45 for the heart was approximately 1.5% and V60 was 1%. Finally, the mean dose to the larynx was 15.68 Gy. The brachial plexus and spinal cord were highly prioritized to avoid overdose. Due to the permissible dose to these structures, the radiation oncologist accepted the plan and normalization value. The medical dosimetrist encountered difficulties in accomplishing the given constraints in the plan designed for Patient 2. The constraint of the brachial plexus was successfully attained with the maximum dose observed at 65.99 Gy. The spinal cord received a maximum dose of 43.3 Gy. The V20 for the right lung was 24.7% with the mean dose was observed at 15.22 Gy. The V20 for the left lung was 1.5% with the mean dose observed at 3.8 Gy. The final mean dose for the esophagus was perceived at 13.76 Gy. While the critical structure dose limitations were accomplished successfully, the dose to the PTV was compromised (Figure 8). Department protocol specifies that 95% of the PTV receive prescription dose, however, this plan demonstrated only 73.6% of the PTV received prescription dose. Due to the proximity of brachial plexus, the radiation oncologist accepted the underdosed PTV regions with a normalization value of 99.2% (Figure 8). The dose delivered to PTV for Patient 3 was also compromised to meet critical structure limitations. As the highest priority structure, the brachial plexus received a maximum dose of 60.01 Gy. Subsequently, the expanded spinal cord received a maximum dose of 43.75 Gy. The V20 for the total lung volume was observed at 27%. While the dose limitations expressed the V20 to be less than 25%, the radiation oncologist reduced the restriction and accepted 27%. In addition, the mean lung dose and V5 dose were remarked at 13.79 Gy and 46% respectively. The mean esophageal dose exceeded the given dose constraint at 34.47 Gy. However, the physician

11 accepted the elevated dose because of the close tumor proximity. Due to the physicians conservative dose constraints, the PTV dose coverage was significantly compromised (Figure 9). Approximately 89.6% of the PTV received 60 Gy, however, the plan was desirable and the physician accepted with a normalization of 96.5%. Though Patient 4 was given a lower prescription dose, PTV coverage was compromised superiorly to meet the physicians constraints for the dose limiting structures. The brachial plexus and expanded spinal cord received maximum doses of 60.3 Gy and 44.59 Gy respectively. The total lung V20 was observed at 32%, V5 was observed at 65% and the mean total lung dose was observed at 19.27 Gy. Although the physicians desired objectives were not obtained, the percentage was acceptable due an unusually low total lung volume. The mean heart and esophageal doses were remarked at 15.38 Gy and 34.57 Gy, respectively. While the heart constraints were well within tolerable limits, the esophageal dose was exceedingly high. The physician observed the overdosed esophageal areas and accepted the higher mean volume. With the brachial plexus limitations, the PTV dose was significantly compromised (Figure 10). The percentage of PTV receiving prescription dose was noted at 75%, however, the percentage of PTV receiving 57 Gy was observed at 98.6%. The physician accepted the PTV coverage with a normalization of 98%. The sacrificed PTV dose for brachial plexus limitation is most noticeably observed in Patient 5. The brachial plexus constraint was not attained with a maximum dose of 62.11 Gy. The physician examined where the brachial plexus exceeded 60 Gy and confirmed the overdose was a maximum point dose in the structure and was, therefore, acceptable. The spinal cord was observed at 43.61 Gy and within the dose limitation. The lung, heart and esophageal doses were all within the given constraints. The V20 and mean lung doses were observed within dose tolerance at 33% and 19.90 Gy, respectively. The esophagus mean dose was observed at 25.29 Gy. Finally, the heart V60 was noted at 2%, the V45 was observed at 3% and the V40 was noted at 4%. As noted, the PTV dose was significantly compromised to account for the brachial plexus (Figure 11). The percentage of the PTV that received prescription dose was noted at 87%. After further review, the physician confirmed that 99% of the PTV received 60 Gy and accepted the normalization of 97%.

12 The greatest difficulty in obtaining an acceptable dose distribution and adequately limiting dose to the brachial plexus was observed in Patient 2-5. In all patients, the prescription dose exceeded the limitations of the brachial plexus, thus modifications were required (Figures 8-11). The superior aspects of the PTVs for Patients 2-5 were significantly underdosed to adhere to the radiation oncologists directives. While the PTV overlapped the brachial plexus on Patient 1, the restrictions on the brachial plexus were less conservative and aided in achieving improved dose homogeneity in the PTV (Figures 6 and 7). The DVH comparison in Figures 12-16 demonstrate the respective dose curves of patients 1-5. To evaluate the PTV coverage, the maximum dose, minimum dose and percentage of PTV receiving 100% of the prescription dose were evaluated. As specified initially, the dose coverage was not compromised in the area of the brachial plexus for Patient 1 as indicated in Table 3. A statistical analysis demonstrated that the amount of PTV receiving prescription dose for the PTVUpLungNodule and PTVMidLungNodule was 95.3% and 99.6%, respectively (Table 3). Considering the department protocol indicated 95% of PTV receives 100% of the dose, both of PTVs were adequately dosed. Table 4 was indicative of the PTV dose coverage for Patient 2. The underdosed PTV in the superior aspect of the lung was directly responsible for the reduced percentage of PTV receiving prescription dose. Although the coverage was undesirable, the plan was acceptable per physician guidelines. The dose evaluation for Patient 3 was similar to Patient 2. The underdosed portions of the PTV due to the proximal brachial plexus impacted the prescription dose coverage. The coverage was observed at 89.6%, approximately 5.4% under department protocol (Table 5). However, the plan was considered acceptable because the brachial plexus and spinal cord constraints were upheld. Patient 4 encountered similar planning limitations to Patients 2 and 3. The brachial plexus and PTV dose requirements were discordant making the structure overlap difficult to attain. The superior PTV was significantly underdosed, contributing to only 75% tumor coverage (Table 6). Again, in this case the physician acclimated department protocol to account for brachial plexus limitations and the plan was acceptable. Table 7 is indicative of PTV dose for Patient 5. While curative doses were administered, the superior PTV experienced at least a 6 Gy decrease in tumor dose to account for brachial plexus limitations. Approximately 87% of the PTV was receiving prescription dose, altering department protocol (Table 7). The plan was considered agreeable because the highest priority of sparing the brachial plexus was attained.

13 To ensure each plan was treatable and to verify monitor units (MU), all plans were transferred to the treatment console and administered the quality assurance (QA) program MapCheck 6.2.3. Each of the plans were within tolerance (3%) of the TPS calculations. The MUs were also within tolerance (5%) based on department protocol. Results and Discussion In each case, the prescription dose was compromised to achieve the restrictions for the brachial plexus. Patient 1 was treated to a lower dose to ensure RIBP would not develop. While the dose homogeneity was sufficient based upon the literature and department protocol, the American College of Radiology (ACR) criteria suggests that 60-70 Gy is most suitable for these types of patients.9 A typical dose prescription for this type of patient is 63 Gy per department guidelines, however, the physician exercised dose restraint due to the proximity of the brachial plexus and spinal cord. Patient 2 was treated to higher dose of 66 Gy for the opportunity to cure the disease. However, dose homogeneity and PTV coverage was compromised to meet the limitations of the brachial plexus dose. Sura et al,10 suggests that inoperable patients with advanced stage NSCLC can be treated up to 80 Gy for curative intent. Case in point, the high radiation dose for cure was compromised due to the proximity of the brachial plexus and limitations. Patient 3 was treated to a lower dose prescription of 60 Gy for local control of the disease. In addition, the superior aspect of the PTV was underdosed further to avoid the brachial plexus. Patient 4 was also given a palliative dose to avoid compromising quality of life. Although the inferior PTV was successfully covered by prescription dose, the superior aspect of the PTV was notably compromised leading to 3 Gy decrease in dose around the brachial plexus location. Patient 5 experienced a compromised curative dose. The physician opted to treat the patient to 66 Gy, however, this patient also experienced brachial plexus invasion that limited the superior aspect of the PTV to a lower dose. In all cases, the brachial plexus was the primary restriction to treating each patient to a higher dose. While the treatment technique of IMRT has assisted on delivering dose around the brachial plexus sequentially, the patients with entire brachial plexus invasion are incapable of receiving adequate therapeutic dose per current guidelines. As these cases become more prevalent, research has expanded the mindset on dose limitations of the brachial plexus. Eblan et al,11 recently suggested that for patients with apical inoperable, extensive stage NSCLC, the brachial plexus may be treated to a dose of 66-74 Gy with a

14 maximum dose less than 78 Gy. A study by Hall et al,12 analyzing brachial plexus dose for head and neck patients, also suggested that the structure could indeed receive doses exceeding current parameters. With this information in mind, the dose prescription for similar patients in the future is now arguable. Radiation induced brachial plexopathy is a devastating side effect if care is not taken. However, the opportunity of disease control is compromised and could be a side effect of cautionary low doses as well. In fact after consult with the physicians, each stated that the major limiting factor in dose prescription was the brachial plexus and higher radiation could have been delivered to each patient if it were absent. A future case study would be ideal to explore the follow-up with these patients including disease control, cure, recurrence and morbidity.

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Figures

Figure 1. Expanded brachial plexus (purple) overlapping the superior aspect of the PTVUpLungNodule (cyan) for Patient 1.

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Figure 2. Expanded brachial plexus volume (pink) detracted from PTV volume (cyan) for Patient 2. The overlapped area is denoted in blue.

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Figure 3. Expanded brachial plexus (purple) overlapping the superior aspect of the PTV (cyan) for Patient 3.

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Figure 4. Expanded brachial plexus (yellow) overlapping the superior aspect of the PTV (cyan) for Patient 4.

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Figure 5. Brachial plexus (blue) overlapping the superior aspect of the PTV (red) for Patient 5.

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Figure 6. Isodose distribution for Patient 1 in the superior aspect of the PTVUpLungNodule (cyan) with expanded brachial plexus overlap (purple). (Red = 61.2 Gy, Green = 58.14 Gy, Blue = 45 Gy, Yellow = 30 Gy, Orange = 20 Gy)

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Figure 7. Isodose distribution for Patient 1 of the inferior aspect of PTVUpLungNodule (cyan) and PTVmidLungNodule (magenta). (Red = 61.2 Gy, Green = 58.14 Gy, Blue = 45 Gy, Yellow = 30 Gy, Orange = 20 Gy)

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Figure 8. Isodose distribution for Patient 2 in the superior aspect of PTV (cyan) with dose sculpted around the brachial plexus (yellow). (Red = 66 Gy, Purple = 64.68 Gy, Yellow = 62.70 Gy, Orange = 60 Gy, Light Green = 45 Gy, Dark Green = 20 Gy).

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Figure 9. Isodose distribution for Patient 3 in the superior aspect of PTV (cyan) with dose sculpted around the brachial plexus (purple). (Green = 63 Gy, Red = 60 Gy, Yellow = 57 Gy, Purple = 50 Gy, Pink = 45 Gy, Orange = 40 Gy, Cyan = 20 Gy).

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Figure 10. Isodose distribution for Patient 4 in the superior aspect of PTV (cyan) with dose sculpted around the brachial plexus (yellow). (Light Green = 63 Gy, Red = 60 Gy, Purple = 57 Gy, Pink = 45 Gy, Dark Green = 20 Gy, White = 5 Gy).

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Figure 11. Isodose distribution for Patient 5 in the superior aspect of PTV (red) with dose sculpted around the brachial plexus (dark blue). (Light Green = 69.3 Gy, Yellow= 66 Gy, Purple = 62.7 Gy, Cyan = 60 Gy, Dark Green = 45 Gy, Orange = 30 Gy, Red= 20 Gy.

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Figure 12. DVH display of brachial plexus (purple), spinal cord (green) , PTVmidLungNodule (magenta) and PTVUpLungNodule (cyan) for Patient 1.

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Figure 13. DVH display of brachial plexus (yellow), spinal cord (green) and PTV (cyan) for Patient 2.

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Figure 14. DVH display of brachial plexus (purple), spinal cord (green) and PTV (cyan) for Patient 3.

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PTV

Brachial Plexus

Spinal Cord

Figure 15. DVH display of brachial plexus (yellow), spinal cord (purple) and PTV (cyan) for Patient 4.

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PTV

Brachial Plexus

Spinal Cord

Figure 16. DVH display of brachial plexus (cyan), spinal cord (green) and PTV (red) for Patient 5.

31 Tables Table 1. Treatment planning details for Patients 1-3. Prescription and Treatment Planning Parameters Case Site Patient 1 Left lung apex with mediastinal and supraclavicular nodal involvement Patient 2 Right lung apex and chest wall invasion Patient 3 Right lung apex and mediastinal nodal involvement

Prescription Beam Energy Prescription Dose 6MV 61.2 Gy in 34 Fx (Both PTVs treated to this dose) 6MV 66 Gy in 33 Fx 6MV 60 Gy in 30 Fx

Treatment Planning Parameters Beam arrangement Gantry Angles Collimator Angles (Respective to gantry angles above.) Planning Technique (7) Co-planar beams 330, 0, 30, 60, 120, 170, 225 10, 10, 6.5, 356.6, 331.4, 342.9, 9.1 IMRT (7) Co-planar beams 212, 279, 318, 0, 48, 77, 150 0 IMRT (7) Co-planar beams 200, 250, 300, 0, 50, 100, 150 0 IMRT

32 Table 2. Treatment planning details for Patients 4 and 5. Prescription and Treatment Planning Parameters Case Site Patient 4 Left lung apex with mediastinal invasion Prescription Beam Energy Prescription Dose 6 MV 60 Gy in 30 Fx Treatment Planning Parameters Beam Arrangement Gantry Angles Collimator Angles (Respective to gantry angles above.) Planning Technique (7) Co-planar beams 204, 255, 306, 0, 51, 102, 153 345, 335, 337, 0, 21, 20, 14 IMRT (5) Co-planar beams 220, 345, 25, 145, 175 0 IMRT 6 MV 66 Gy in 33 Fx Patient 5 Right lung apex with brachial plexus extension

33 Table 3. PTV dose evaluation for Patient 1. PTV Evaluation for Patient 1 Prescription Dose (Gy) PTVUpLungNodule PTVMidLungNodule 61.20 61.20 Maximum Dose (Gy) 64.77 65.74 Mean Dose (Gy) 62.23 63.27 Percentage of PTV receiving 100% of Prescription Dose 95.3% 99.6%

Table 4. PTV dose evaluation for Patient 2. PTV Evaluation for Patient 2 Prescription Dose (Gy) PTV 66 Maximum Dose (Gy) 70.28 Mean Dose (Gy) 66.19 Percentage of PTV receiving 100% of Prescription Dose 73.6%

Table 5. PTV dose evaluation for Patient 3. PTV Evaluation for Patient 3 Prescription Dose (Gy) PTV 60 Maximum Dose (Gy) 65.85 Mean Dose (Gy) 62 Percentage of PTV receiving 100% of Prescription Dose 89.6%

Table 6. PTV dose evaluation for Patient 4. PTV Evaluation for Patient 2 Prescription Dose (Gy) PTV 60 Maximum Dose (Gy) 69.76 Mean Dose (Gy) 61.23 Percentage of PTV receiving 100% of Prescription Dose 75%

34 Table 7. PTV dose evaluation for Patient 5 PTV Evaluation for Patient 2 Prescription Dose (Gy) PTV 66 Maximum Dose (Gy) 72.81 Mean Dose (Gy) 67.39 Percentage of PTV receiving 100% of Prescription Dose 87%

35

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