Dosimetric Evaluation of Planning Techniques in Lung SBRT Authored by: Toby Shutters, B.S. RT(R) (T) Indiana University School of Medicine Medical Dosimetry Graduate Certificate Program Indianapolis, Indiana   Co-Authored by: Jeannie Jimerson, M.S. RT (T), CMD Richard Roudebush VA Medical Center

SBRT Hypofractionation High Conformality Steep Dose Gradients SBRT: a technique that employs dose escalation along with hypofractionation by delivering higher doses per fraction for fewer fractions . Hypofractionation allows for better tumor control by having more of a biological effect compared to conventional dose.High conformality and steep dose gradients are other factors important to the efficacy of SBRT.5 Several parameters contributing to maintaining conformality and steep dose gradient are minimal margin around the PTV, number of beams, beam weighting, and beam energy.

Stereotactic Body Frame In 1994, extracranial stereotactic body radiation therapy, SBRT, was further improved when Ingmar Lax and Henric Blomgren from the Karolinska Institute in Sweden developed the Stereotactic Body Frame.3,4 The device provided reproducible immobilization as well as incorporated a stereotactic fiducial system utilized to define the coordinates of the target.3,4 It was designed to reduce internal movement of the target and surrounding organs while immobilizing the patient to ensure target accuracy.4,6 http://www.erasmusmc.nl/radiotherapie/patientenzorg/behandelmethoden/uitwendigebestraling/128828/314368/

Non-small Cell Lung Cancers (NSCLC)

Surgical Options Lobectomy Wedge resection or segmentectomy Comorbidities Lung cancer is the leading cause of cancer death in the US with the optimal chance for cure existing in early stage non-small cell lung cancers, NSCLC.7,8 NSCLC are usually surgically resected with a lobectomy offering survival rates of 60%-80% in 3-5 years.2 Another surgical option may include wedge resection or segmentectomy, but they do not offer the survival outcomes that are associated with the more aggressive lobectomies. 2,9 Surgery can result in significant complications. Complications are further increased for those patients with comorbidities such as age, poor pulmonary function, and cardiovascular disease.2, 8 Comorbidities can also limit aggressive surgical treatment options needed for improved disease control. Extensive comorbidities can exclude patients from any surgical options. Alternatives to surgery include the use of external beam radiation.

Conventional External Beam Radiation SBRT Conventional External Beam Large Daily Fractions Total Fractions 1 to 5 3 year local control rates of up to 98% Increases in late toxicities Small Daily Fractions Total Fractions 27 to 33 5 year survival rate of 10 to 30% Conventional external beam radiation utilizes small daily fractions of 1.8-2 Gy for a total of 50-66 Gy with dismal 5 year survival rates of 10%-30%.2,7, 10 SBRT, another external beam approach, utilizing hypofractionation treatment delivering larger doses per fraction are delivered between one and five fractions. SBRT offers superior 3 year local control rates of up to 98%.9,11,12,13 Along with higher fraction dose, increases in late toxicities can be seen.14 Another alternative to surgery that medically inoperable patients can elect is to be managed by observation alone. Unfortunately, five year survival rates for observation alone are less than 10%.1, 8, 10

Location Dosimetrically challenging Late toxicities Tumors adjacent to the chest wall area Deliver high conformal doses Minimize critical structure doses Late toxicities Chest wall pain Rib fractures For those patients with tumors that are adjacent to the chest wall area, it can be dosimetrically challenging to deliver conformal high doses to the target volume while minimizing the dose to the adjacent ribs and chest wall region. Over irradiation of the chest wall can result in late toxicities such as rib fractures and chest pain.9, 13

Toxicities Natonal Institute Common Terminology Criteria for Adverse Events Grade 1 Mild pain Grade 2 Moderate pain Grade 3 Severe pain Grade 4 Disabling pain These toxicities are scored according to the National Institute Common Terminology Criteria for Adverse Events. Grade 1 is mild pain not interfering with function. Grade 2 is moderate pain; pain or analgesics interfering with function but not interfering with activities of daily life. Grade 3 is severe pain; pain or analgesics severely interfering with activities of daily life. Grade 4 is disabling pain.9,15

Doses Andolino et al Dunlap et al 10% risk of grade 1 or greater at 30 Gy with 15cc’s 30% risk at 30 Gy with 40 cc’s 50 Gy greater incidence of rib fracture or chest wall pain Dunlap et al 30 Gy in 3-5 fractions should be less than 30cc’s 50 Gy greater incidence of rib fracture or chest wall pain Andolino et al13 predicted a 10% risk of grade 1 or greater reaction when 15 cc's of chest wall received 30 gy and a 30% risk at 30Gy with 40 cc's.13 The study also demonstrated 50 Gy was the maximum dose where the incidence of rib fracture and chest wall pain was more likely to occur. Another study by Dunlap et al1 demonstrated that the chest wall volume receiving 30 Gy in 3-5 fractions should be limited to less than 30 cm3.1 Their results also indicated chest wall pain and rib fracture were more likely at or above the 50 Gy dose.1

Dosimetric Evaluation This study retrospectively analyzed three planning techniques to determine if a there was a dosimetric advantage utilizing noncoplanar geometry. All five patients had adjacent or invasive chest wall lesions. The plans were evaluated using the Conformality Index from RTOG 0813 and 0915. Chest wall and rib volumes were examined at V30Gy, V45Gy, and V50Gy.

Methods and Materials 5 patients with adjacent chest wall tumors Eclipse Version 8.0 Elekta Bodyframe GTV’s and PTV’s OAR’s through RTOG protocols Evaluation of dose Five patients with peripheral tumors adjacent to the chest wall were treatment planned utilizing Eclipse version 8.0 software. All patients were immobilized in an Elekta bodyframe. The GTV's were delineated by the Radiation Oncologist. PTV volumes were created using a margin to the GTV of 0.5 cm radially and 1 cm superior and inferior. The dosimetrist contoured the organs at risk, OAR, as specified through RTOG protocols 0915, 0236, and 0813.16 These organs include: heart, esophagus, spinal cord, proximal bronchial tree, trachea, whole lung, Great vessels as well as the ipsilateral brachial plexus were contoured for upper or middle lobe lesions. The doses to the OAR's were evaluated using RTOG constraints for four fractionations delivering a dose of 1200 cGy per fraction.16

Methods and Materials, continued Two sets of blocks Modifications to blocks and weighting of PTV 95% of the PTV volume covered by prescription Most common isodose 80% Two sets of blocks were designed for field in field coverage of the GTV and PTV. All fields used 6MV photons. The larger block treating the PTV was weighted more heavily than the smaller field in field to provide coverage but maintain steep dose gradient and dose fall off. The smaller field in field block was an expansion of the GTV to 1 cm superiorly and inferiorly without any axial margin. There were modifications to the blocks and weighting for optimal coverage of the PTV. The plan was prescribed to the isodose line that allowed for 95% of the PTV volume to be covered by the prescription dose. The most common isodose line chosen was the 80%.

Three Planning Techniques Coplanar (COP) No couch rotations Mixed Planar (MP) Some couch rotations, some not Non-coplanar (NCP) All couch rotations

Three Planning Techniques: COP Field Label Gantry Angle Couch Rotation AP RAO 333 333 RAO 305 305 RAO 278 278 RPO 250 250 RPO 223 223 RPO 195 195 LPO 168 168 LPO 140 140 LPO 113 113 LAO 85 85 LAO 58 58 LAO 30 30 The first technique coplanar, COP, consisted of thirteen 360 degree coplanar rotations. The gantry angles utilized were 0, 333, 305, 278, 250, 223, 195, 168, 140, 113, 85, 58, and 30 degrees. All COP plans used these particular gantry angles. The COP technique offers shorter treatment times which can be optimal for patient comfort and therefore less movement.7, 12

Three Planning Techniques: MP Field Label Gantry Angle Couch Rotation RPO 210 RT LAT 270 RAO 315 AIO 340 90 ASO 30 LAO 50 LSO 20 LIO LPIO 160 PA 180 Next, the second technique focused on a mixed technique, MP, of 10 coplanar and noncoplanar beams. These beams have a mixture of zero couch rotations and couch rotations. The gantry angles utilized for a right lower lobe are listed as an example in the table 1 below. Gantry and couch angles may have been modified to accommodate left or right side target volumes. Collisions between patient and gantry become an issue when using couch rotations depending on target volume location. Some immobilization devices increase the likelihood of collision so it is imperative to ensure these angles can be accomplished prior to patient treatment. MP technique offers a slightly longer treatment time than the COP beam arrangement to allow for the therapists to enter the treatment room to safely rotate the gantry and couch.

Three Planning Techniques: NCP Field Label Gantry Angle Couch Rotation LPSO 2 160 50 LPSO 1 122 18 LAIO 2 101 345 LASO 1 79 15 LAIO 1 58 342 37 16 19 306 RASO 2 350 RAIO 2 323 26 RASO 1 302 RAIO 1 281 10 RPSO 2 259 RPIO 1 238 RPSO 1 217 Finally, the last technique, noncoplanar, NCP, consisted of 14 noncoplanar beams. There was a mixture of couch and gantry angles to maximize dose distribution to the target volume and spare the OAR's. This ensures that beam entry and exit can be maximally separated increasing dose conformality.7,10 The gantry and couch angles utilized for the same right lower lobe patient as an example are listed in figure 2 below. Gantry and couch angles may have been modified to accommodate left or right side target volumes. Unfortunately, this technique provided the most opportunity for collision between the patient and gantry especially with the most anterior and posterior target volumes. Prior verification is essential but it may vary with each individual patient and tumor location since most of them are elderly with various other health issues and limited ranges of motion. This technique offers the longest treatment time compared to COP or MP due to 14 different gantry and couch angles the therapist has to enter the room to ensure safety between beams. 4, 12

Plan Evaluations 4 fractions of 12 Gy for total of 48 Gy 95 % coverage of PTV RTOG 0915 for OAR verification Chest wall/rib volume at 2cm contour DVH at V10 Gy, V30 Gy, V45 Gy, and V50 Gy Conformality Index All plans were reviewed for coverage to 95% of the PTV. The dose schema was 4 fractions of 12 Gy for a total dose of 48 Gy. Then, the critical structure dose limits from RTOG 0915 for the OAR'S were verified for acceptability.16 These included the spinal cord, heart, proximal bronchial tree, esophagus, trachea, and the whole lung V20. The ipsilateral brachial plexus and great vessels were reviewed if they were in the area of the target volume. One patient did not meet the criteria for great vessel doses due to the proximity of the target volume to the aorta. In addition to the above RTOG structures, the adjacent chest wall and rib volume were contoured and evaluated. The chest wall was a 3 dimensional volume expansion measuring 2 cm excluding the mediastinum, ipsilateral lung, and vertebral body. The ribs were contoured in a separate volume to measure the dosimetric impact to them. In Mutter et al15, their results demonstrated the chest wall dose and volume at 2cm3 better predicted chest wall pain than a 3cm3 margin.15 This suggests the neurovascular structures, muscle, and ribs are more indicative of pain than the larger volume encompassing the soft tissue.1, 15 Dose volume histograms, DVH, were reviewed for the chest wall and ribs at the V10 Gy, V30 Gy, V45 Gy, and V50 Gy. Volumes in cc's were measured for the chest wall and ribs for comparison between the 3 techniques. The Conformality Index, 16 CI, acccording to the ICRU 62 is the prescription isodose volume to the PTV volume.4 It was calculated using the volume at 48 Gy divided by the PTV volume for each of the 3 techniques planned per patient.16 The CI for an ideal plan is 1 but values can go up to 2.5An index below 1 indicates there is less than 95% coverage for the PTV. Likewise, an index above 1 indicates the volume treated to 95% is greater than or equal to the PTV.16 These were then evaluated according to the RTOG 0813 and 0915 protocol requirements for meeting the criteria.

Results Conformality Index (CI) RTOG 0813 and 0915 Optimum CI less than 1.2 Minor Deviations between 1.2 and less than 1.5 All three techniques Optimal or minor deviations 40% or 6 out of 15 optimal MP: met 1.2 for all but one patient COP and NCP: met 1.2 one patient each The CI was evaluated using RTOG 0813 and 0915 to determine the conformality of each plan. The criteria states it should be less than 1.2 with minor deviations occurring between 1.2 and less than 1.5.16 All three techniques produced plans that were acceptable or had minor deviations. 40% or six out of the fifteen plans met the RTOG optimal criteria of less than 1.2.16 Our results demonstrated that the MP plans met the 1.2 or less RTOG conformality criteria in all but one of the patients. However, the COP and NCP plans only met the optimal criteria in one patient each. Only one patient had all three plans that were minor deviations per RTOG protocol.16 Of these plans, the MP plan was more conformal than the COP and NCP plans.  

Results

Volumes of chest wall irradiated demonstrated little variation with the 3 planning techniques. The following graphs demonstrate the COP plans include more chest wall volume than NCP and MP plans especially at the 45 Gy and 50 Gy levels. At 30 Gy, the volume of chest wall irradiated by the NCP technique demonstrates the least amount of volume in comparison to the COP and MP techniqes. The average amount of total chest wall volume for the five patients was 1664. 7 cc's indicating all of the techniques spare this critical structure. The volume irradiated at 30 Gy according to studies can predict the possibility of chest wall pain predicted a 10% risk of grade 1 or greater reaction when 15 cc's of chest wall received 30 gy and a 30% risk at 30Gy with 40 cc's.13 In our results, eleven of the fifteen plans had equal to or greater than 15 cc's of chest wall. However, Dunlap et al1 found that 30 cc's at 30 Gy in three to five fractions was their predictor of risk.1 None of our chest wall volumes reached the 30 cc mark indicated for risk. As per the data above, there are numerous studies indicating chest wall pain can be an issue after SBRT but absolute values have not been demonstrated.1,13

At 45 Gy, the COP planning technique irradiated the most volume of chest wall for all five patients. The chest wall volume irradiated by the NCP or MP planning techniques appeared to very similar.

At 50 Gy, the maximum volume of chest wall irradiated is almost 4 At 50 Gy, the maximum volume of chest wall irradiated is almost 4.5 cc's with the COP planning arrangement. Andolino et al13 demonstrated in their results, 50 Gy was the dose where the incidence of chest wall pain was more likely to occur.13 Dunlap et al1 demonstrated the same results in their study.1 The chest wall volumes with its corresponding doses necessitate review when planning SBRT. The NCP or MP plans offer essentially the same dose and volumes to the chest wall. Treatment time for the patient needs to be a priority for their comfort and optimal treatment.5, 12 The MP plan with fewer couch rotations would be more expedient than the NCP plan.

The V30 Gy, V45 Gy, and V50 Gy of rib irradiated demonstrated little variation with the 3 planning techniques. The following graphs demonstrate the COP plans include more rib volume. At 30 Gy, the least volume of rib included in the treatment planning is the MP technique. The average rib volume for the five patients was 130. 4 cc's signifing dose sparing to these critical structures. There were indications in some studies that 30 Gy was the benchmark volume for predicting rib fracture. Dunlap et al1 demonstrated that 30 Gy to 30 cc's in three to five fractions be indicative of rib fracture risk.1 Pettersson et al6 found the increased risk for rib fracture to be 5% at 27.2 Gy for 2cc's.6 In our results, thirteen of the fifteen plans had equal to or greater than 2 cc's of rib volume.

At 45 Gy, the COP plan includes the most rib volume while the other two plans are very similar. But at this point, the greatest volume is less than 3.5 cc's.

At 50 Gy, the COP plans demonstrated the most volume of rib irradiated At 50 Gy, the COP plans demonstrated the most volume of rib irradiated. The rib volume irradiated in our study was at most around 3 cc's. Pettersson et al6 found the highest risk of fracture in the high dose low volume region.6 In three fractions, the risk of fracture for 2 cc's of rib was 50% at 49.8 Gy.6

Synopsis Dose/Volume relationship Analysis of three different planning techniques for dose conformality V30 Gy, V45 Gy, and V50 Gy similar for NCP and MP CI was met more often for MP than NCP Studies indicate volume and dose relationship are important factors for the development of late toxicities in SBRT.1, 13We analyzed three different planning techniques for dose conformality and chest wall/ rib volumes. The volumes of rib and chest wall irradiated at the V30 Gy, V45 Gy, and 50 Gy did not vary much between the NCP and MP plans. The CI criteria from RTOG 0813 and 0915 were met more often for the MP plans than the NCP plans.

The low dose region of less than 10 Gy demonstrated that all the plans were conformal to this point. The dose volume histograms were overlaid until 10 Gy when they split off for each planning technique.

Conclusion Cure for early stage NSCLC is surgical Aging population has comorbidities Medically inoperable offered SBRT SBRT has late toxicities Improved survival decrease toxicities Analyzed 3 planning techniques for volumes and conformality NCP offers no dosimetric advantage increases treatment time MP is best option Lung cancer continues to be one of the most prevalent cancers in the United States. The best chance of cure for early stage NSLC includes surgical options which can have complications.7, 8However, the aging population presents with numerous comorbidities such as cardiovascular disease and poor pulmonary function so their options decrease.2, 8 These medically inoperable patients are offered SBRT which offers fewer treatments with a better response rate than conventional external beam.13 With improved survival rates for these patients, late occurring toxicities such as chest wall pain and/or rib fracture need to be analyzed to decrease their occurrence.10,13 We evaluated three different planning techniques for dose conformality and volumes of chest wall and ribs irradiated. There was no dosimetric advantage for increasing the geometric complexity of the plan. NCP with its complexity prolongs treatment times which can result in tumor and patient movement.7, 12 Therefore, for optimal treatment outcome and patient comfort the MP offers the best option.