Development and Evaluation of a Bi-polar Gated Respiratory Motion Management Strategy for Lung SBRT

Abstract

BackgroundStereotactic body radiation therapy (SBRT) is a noninvasive alternative treatment for patients who cannot accept surgery. It delivers higher ablative total radiobiological doses to the tumor in fewer fractions. The dose can be as high as 20Gy per fraction (compared to 1.8 to 2 Gy in conventional radiotherapy treatment) and the number of fractions are usually less than 5 (compared to 30 in conventional treatment). Thus, it requires high conformal dose distribution and minimal exposure of surrounding healthy tissues for the patients. The major challenges of SBRT for lung cancer include respiratory motion, positioning uncertainty and intra-fraction stability. Breath hold is usually not suitable for lung cancer patients because they cannot hold the breath for a long time (typically 20 seconds or more) for treatment. Current treatment strategies for Lung SBRT include free breathing (FB), gating at the end of exhale (GE), gating at the end of inhale (GI), and real-time tracking (RT), which are illustrated in the figure below (Fig.a). Most lung SBRT patients are treated in free breathing. It delivers dose to all the tumor motion trajectory, thus requires field size larger enough to cover all the possible tumor locations, creating extra dose to normal tissue. This results in lesion size limitation, so FB is most widely used in small tumors or tumors with less motion, such as those located in the upper lobes of the Lung. The advantages of FB are its low technical requirements and high treatment efficiency (100% duty cycle). For gating technology, the radiation is limited to several specific respiratory phases at the end of exhale or inhale in which the target motions are reduced. It monitors motion and reduce treatment volume, which offers the dosimetric advantage of lower doses to organs at risk. The duty cycle of gating depends on the threshold and is usually less than 30%. Gated treatment can be executed in two strategies: GE and GI. These two strategies each has their own pros and cons. For GE, the tumor position is typically more reproducible than GI. However, GI has larger lung volume due to inspiration and this can lead to lower lung toxicity. In real-time tracking, the beam moves with the tumor movement and delivers the dose to the exact tumor position. It is the most effective strategy because it has theoretically zero motion margin. Another advantage is high treatment efficiency with the beam always on during treatment. The drawback of RT is that it is highly technical demanding and there may be some time delay in tumor detection, decision making and taking actions. Therefore, it is more complex than other strategies and could result in additional potential errors. In addition, the dose delivery accuracy of real-time tracking is limited by the 4DCT resolution and this will be introduced in the following section.Purpose To reduce the motion margin in dose delivery, we developed a novel bipolar (BP) strategy that requires the patient to hold the breath at the end of the inhale and exhale under audio/video coaching. By only delivering the dose to the tumor during breath-holding, the dose is given to the exact tumor position. This reduces normal tissue toxicities to a great extent. Moreover, the treatment duty cycle is higher than conventional gating technology. In this study, we want to evaluate the feasibility of BP breathing pattern and also compare BP with other strategies geometrically and dosimetricly. Methods BP Feasibility Analysis: Feasibility analysis is conducted to see if the bi-polar breathing pattern is sustainable and comfortable for patients to breathe in a long time. 8 volunteers are included in this study to breathe following the FB/RT, GE, GI and BP breathing patterns under audio coaching. The respiratory signals acquisition time for each pattern is more than three minutes. A custom MatLab program is developed for data analysis. The period repeatability, breath-hold repeatability and treatment efficiency are calculated and compared for each strategy. Geometric Evaluation: 10 previously treated lung SBRT patients with 4DCT were selected retrospectively, each having tumor motion ≥ 1cm. The tumor size at end-exhale (EE) ranges from 0.1 to 22.7 and 80% cases larger than 1cc. 60% tumors located at the lower lobe of the lung. Lung volume and tumor position were used to determine the end-exhale (EE) and end-inhale (EI) phases. The GTV was contoured at each 4DCT phase to determine the ITV for each strategy. PTV is formed by 1mm expansion from ITV. The lung volume, ITV and PTV in BP were compared with FB, GE, GI and RT. All the values are normalized to GI to include all the patients for comparison. Dosimetric Evaluation: IMRT and VMAT plans were generated for each patient with a prescription dose of 60 Gy in 5 fractions. All the plans are completed in the Varian Eclipse System (Version 15.5). The energy we used is 6MV and the calculation algorithm is AAA. 100% dose is normalized to 95% volume. All the plans should meet the RTOG 0813 protocol. IMRT uses 7-9 beams and VMAT uses 1-2 arcs. OARs includes lungs, spinal cord, esophagus, trachea, heart etc., were contoured. For BP and RT, a custom MatLab program was used to summate the plans and calculate the DVHs. Parameters include V5Gy, V13Gy, V20Gy and MLD (mean lung dose) were compared for each strategy in both VMAT and IMRT plans. Tumor Motion Modeling: The purpose of this section is to prove the observed volume in 4DCT is larger than real tumor volume due to tumor motion and the limited number of phases in 4DCT. Both phantom and patient study are included in tumor motion modeling to verify our assumption. QUASAR phantom with a white ball inside (radius: 1.5cm) was used for phantom data acquisition. 5 breathing patterns using same motion amplitude was acquired. The BPM (breath per minute) are 15, 20, 25, 30,33, respectively. 10 previously treated lung SBRT patients with 4DCT were selected for patient study. These patient data are the same as patient data in geometric evaluation section. We developed a MatLab program to calculate the theoretical volume (simulated volume) in each 4DCT phase. By comparing the simulated volume with the observed volume, we want to verify that the observed tumor volume is larger than the real tumor volume in each 4DCT phase and it is a function of real tumor volume and tumor motion.ResultsFeasibility Analysis: BP breathing pattern is found to be comfortable and sustainable over 3 minutes. This may be longer if we test for longer time. The period repeatability and breath-hold repeatability are at 1.00±0.03 and 1.00±0.04. It is higher than GE(with breath-hold) and GI (with breath-hold), indicating a better repeatability for BP. Treatment efficiency of BP can be more than 65% under audio coaching. It may be improved with the video coaching, longer period of breath holding and patient training. Geometric Evaluation: Using GI as reference, ITV in FB is the largest among all 5 strategies and it is significantly larger than BP. That’s because FB delivers dose to the whole tumor motion trajectory thus creating a large tumor motion margin. The ITVs in RT and BP are similar and smaller. They are approximately one third of FB. The ITV in FB is about twice of the ITVs in GE and GI. Generally, PTV shows a similar trend with ITV. FB is significantly larger than other strategies and it is approximately 2.5 times of RT and BP. The PTV of GE and GI are similar and they are about 56% of the FB. BP is a little bit smaller than RT because the fast-moving tumor in limited phases. Comparing with ITV and PTV, they basically follow the same trend. However, the difference between BP and FB are narrowed due to 1mm expansion from ITV to PTV. In PTV, BP is 58% less than FB, and in ITV, BP is 67% less than FB. Dosimetric Evaluation: In IMRT, all the dose are normalized to GI. FB is the highest for V5Gy, V13Gy, V20Gy and MLD in all strategies and BP is significantly smaller than FB. The reason for that is the largest PTV for FB and smallest PTV for BP. V5Gy, V13Gy, V20Gy and MLD in RT and BP are similar and smaller than GE, GI. They are approximately 20%-30% lower than FB. Although GE and GI have similar PTVs, the dose in GI for V5Gy, V13Gy, V20Gy and MLD are much smaller than GE due to lager lung volume in GI. In VMAT, the evaluation parameters are the same as in IMRT. They basically show similar trend with IMRT. The dose for all parameters in FB is the largest and BP is also significantly smaller than FB. RT and BP is similar and smaller and they are approximately 10%-20% lower than FB for all the parameters. These values are smaller than IMRT. Overall, the improvement from FB to BP is slightly larger in IMRT than VMAT.Tumor Motion Modeling:In phantom data analysis, for all the cases, the simulated volume achieves minimum at EE and EI phases due to minimum motion, and it increases with larger motion. Observed volumes agree with simulated volume at most phases. In patient data analysis, the agreement is not as good as phantom. The simulated volume achieves its minimum at EE and EI phases and the tumor volume is larger in other phases. Although the observed volumes do not perfectly agree with the simulated volume for most patient cases, they basically follow the same trend. The possible reasons can be tumor location (connecting to diaphragm or vessels) and patients’ irregular respiratory repeatability. More patient data with clear and isolated margin should be included in the future. Conclusion The respiratory experiment demonstrates that the bi-polar breathing pattern is feasible for lung SBRT. It can sustain a long treatment time with a high duty cycle. Moreover, compared to the breathing pattern of GE and GI, BP is more regular, comfortable and thus more sustainable than other breathing patterns. The tumor volume in each 4DCT phase can be inaccurate due to tumor motion and limited resolution in 4DCT. It is actually a function of real tumor volume and tumor motion. Thus, the treatment volume in RT overestimates the actual tumor volume since it used the observed volume as GTV. For the tumors with larger motion (≥1cm) in this research, BP has a significantly smaller ITV in geometric evaluation; therefore, a smaller treatment volume (PTV) compared to FB, GE and GI. The dosimetric evaluation of IMRT and VMAT shows lower V5Gy, V13Gy, V20Gy, and MLD in BP, especially when comparing to FB. This will lead to lower lung dose in treatment. RT has similar geometric and dosimetric results with BP. However, RT is more complicated than BP in implementation and dose delivering.