Comparison of dosimetric parameters and delivery accuracy between conformal radiotherapy-intensity modulated radiotherapy-combined and intensity-modulated radiotherapy planning for central lung cancer patients receiving stereotactic body radiotherapy

Introduction

Lung cancer remains one of the most frequently diagnosed malignant diseases threatening human physical and mental health (1,2). Radiation therapy is one of the core treatment modalities for it. According to clinical guideline (3), its indications cover all clinical stages of the disease. Stereotactic body radiotherapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), is a high-dose, hypofractionated radiotherapy modality for treating tumor. Compared with conventional radiotherapy, SBRT has a high fractionated dose, short treatment courses, steep dose drop gradient, low exposure to surrounding organs-at-risk (OARs), and good local control (4-6). SBRT has become the standard of care for patients with early-stage non-small cell lung cancer who are not suitable for surgery or refuse surgery (7-9). Several studies have shown that good local control and long-term survival have also been achieved with SBRT in patients with stage IV oligometastatic tumors (10-12).

Traditionally, SBRT has been mainly used for peripheral lung cancer, but current clinical guidelines have also recommended its application in central lung cancer (13). Radiation Therapy Oncology Group (RTOG) defined central lung cancer as lung cancer with lesions located within a volume 2 cm in all directions around the proximal bronchial tree (14-17). Compared with peripheral lung cancer, central lung cancer lesion is usually located at a deeper site and in close proximity to more OARs. Therefore, the toxicity of central lung cancer treated with SBRT has attracted increasing attention. A meta-analysis by Senthi et al. (18) found that treatment-related mortality rate was 1.0% when a prescribed dose of 60 Gy/8 fractions was used. The results of the study found that the use of 60 Gy/8 fractions for the treatment of central lesions was reassuring (19,20). Three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) are commonly used SBRT modalities for lung cancer treatment. 3DCRT has lower planning complexity and exhibits stronger stability to dose calculation, respiratory motion, and interplay effects (21). 3DCRT adopts a forward optimization method, with radiotherapy plan quality being highly dependent on the experience of planner. Moreover, some studies have shown that 3DCRT is less protective of OARs on the premise of meeting the target’s requirements. Not every patient receiving SBRT treatment can use 3DCRT technique. IMRT adopts an inverse optimization approach, which is more advantageous in terms of homogeneity of plan quality. IMRT plans have a high degree of modulation and are more complex, often involving smaller and more irregular beam apertures, and larger tongue and groove effects (22), resulting in slightly poorer agreement between planned and delivered dose (23). A simplified planning strategy for hybrid lung SBRT, named conformal radiotherapy-intensity modulated radiotherapy-combined (Co-CRIM), was previously developed (23). It combines the advantages of 3DCRT and IMRT techniques to achieve a less complex radiotherapy plan through an inverse optimization approach. The clinical utility of this approach has been demonstrated for peripheral lung SBRT, but it has not been proven in central lung cancer.

In this study, Co-CRIM and IMRT methods were used to design radiotherapy plans for central lung cancer patients treated with SBRT, based on two different linear accelerators. The feasibility of the Co-CRIM method in central lung cancer was evaluated by comparing the differences of dosimetric parameters and delivery accuracy between the two plans delivered by the same accelerator. In addition, comparing the dosimetric parameters and delivery accuracy of different accelerator can explore the generalizability of the Co-CRIM method and provide data to support the application of the Co-CRIM method in the clinics.

Methods

Patient characteristics

From August 2021 to March 2023, 20 patients with central lung cancer who underwent SBRT in Shanghai Chest Hospital were included in this retrospectively study. All the patients were randomly selected. The reporting of this study conforms to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines (24). All patients were assessed by radiation oncologists to be unable to undergo surgery or refused surgery. The mean age of the patients was 68.35 years old (range, 47 to 82 years), with 11 males and 9 females. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Shanghai Chest Hospital (No. KS24052). Since it was a retrospective study, written informed consent was waived. Patient characteristics were summarized in Table 1.

Image acquisition

All patients were immobilized in the supine position, and depending on the tumor location, the arms were placed on both side of the body using a thermoplastic mask for postural immobilization or the arms were raised and crossed over the forehead using a vacuum pad for postural immobilization. CT scan was performed with the Siemens Somatom Definition AS computed tomography (CT) scanning system (Siemens Healthcare GmbH) under free-breathing conditions. The scanning range was from the upper edge of the second cervical vertebra to the lower edge of the second lumbar vertebra, and 10 respiratory phases were reconstructed with a slice thickness of 3 mm. The 4D-CT datasets were transmitted via the network to the MIM Maestro workstation (MIM Vista Corp, Cleveland, US-OH).

Target and organs-at-risk (OARs) delineation

The target and OARs for all patients in this study were manually delineated by junior radiation oncologist and reviewed by experienced radiation oncologist on MIM Maestro workstation. The gross tumor volume (GTV) was contoured on each of 10 respiratory phases of 4DCT, and the internal target volume (ITV) was generated by combining the 10 GTVs. Planning target volume (PTV) was generated by isotropically expanding the ITV by 5 mm. All OARs were delineated on average intensity projection (AIP). AIP, PTV and OARs were transferred to Pinnacle 9.10 treatment planning system (TPS) (Philips Healthy, Fitchburg, WI, USA) for design of treatment planning.

Treatment planning generation

Co-CRIM employs the IMRT inverse optimization process in Pinnacle treatment planning system, applying multiple constraints on the maximum number of segments (i.e., the upper threshold for the total number of segments), the minimum segment area (i.e., the lower threshold for all segment areas), and the minimum segment monitor units (MUs) (i.e., the lower threshold for the MUs of each segment). Specifically, the maximum number of segments is set equal to the total number of fields, ensuring one segment per field. The minimum segment area is limited by ITV, and the minimum segment MUs is set equal to the fractional dose (cGy) divided by twice the total number of fields. Plans generated using the Co‑CRIM technique consist of only one sub-field per field, in which the jaw and MLC positions for each field are derived via inverse optimization‑based intensity modulation.

The Co-CRIM and IMRT plans for each patient were designed in Pinnacle 9.10 TPS. Varian Edge and TrueBeam linear accelerator were adopted with 6MV photon beam. The Co-CRIM and IMRT plans delivered with Edge accelerator were named Co-CRIM-E and IMRT-E, and the Co-CRIM and IMRT plans delivered with TrueBeam accelerator were named Co-CRIM-T and IMRT-T. Both accelerators were equipped with 60 pairs of multileaf collimator (MLC). The width of the middle 32 pairs of MLC in Edge was 0.25 and the width of both sides was 0.5 cm. The width of the middle 40 pairs of MLC in TrueBeam was 0.5 and the width of both sides was 1 cm. According to the location of the PTV and the actual situation of the patient, each plan includes 10 or more fields. To compare the differences between the Co-CRIM and IMRT plans, the number of fields, field orientation, and inverse optimization function for one patient were the same. When optimizing the plan, set the highest priority for PTV, the second priority for OAR, and the lowest priority for gradient loops. The optimization algorithm used was direct machine parameter optimization (DMPO), with collapsed cone convolution (CCC) algorithm for dose calculation and a maximum dose rate of 600 MU/min. Each patient was prescribed a dose of 60 Gy/8 fx with a single fraction dose of 750 cGy and delivered once daily. To compare the different plans equally, each plan was normalized to ensure that at least 95% of the PTV received 100% of the prescribed dose.

Planning evaluation

Dosimetric parameters of PTV for Co-CRIM-E, IMRT-E, Co-CRIM-T and IMRT-T plans included conformity index (CI), ratio of 50% prescription isodose volume to the PTV volume (R50), maximum dose (in % of dose prescribed) at 2 cm from PTV in any direction (D2cm) and the ratio of maximum dose (Dmax) to prescription dose (Dp). CI was defined as the ratio of prescription isodose volume to the PTV volume, R50 was defined as the ratio of 50% prescription isodose volume to the PTV volume, and D2cm was defined as maximum dose at 2 cm from PTV in any direction. The parameters evaluated for the OARs included the maximum dose to the spinal cord (Dmax), the dose corresponding to 0.35 cc of the spinal cord (D0.35cc), and the dose corresponding to 1.2 cc of the spinal cord (D1.2cc), mean lung dose (MLD), percentage of the total lung volume receiving more than 10 Gy (V10), 12.5 Gy (V12.5), 13.5 Gy (V13.5) and 20 Gy (V20), Dmax, V32 and D15cc of heart, volume of the esophagus receiving more than 36.8 Gy (V36.8Gy), Dmax of esophagus, Dmax and V32.8Gy of brachial plexus, Dmax and V50Gy of trachea and large bronchus, Dmax and V50Gy of rib. According to the guideline (25), the specific dose constraints for each OARs are shown in Table 2. In addition, the complexity of each plan was assessed using modulation factor (MF), defined as the ratio of MU to the prescribed dose. The higher the MF, the higher complexity of the plan. We also calculated the average number of sub-fields per field.

Delivery accuracy

To validate the delivery accuracy of Co-CRIM and IMRT plans, this study also evaluated the gamma passing rate (γ) for each plan. γ passing rate was assessed under the standard of 2 mm/2% (10% low dose threshold) with Varian on-board measuring device portal dosimetry (PD, Varian Medical Systems). The Eclipse system (Varian Medical Systems, Palo Alto, CA) was used to compare the difference between the delivered and planned dose.

Statistical analysis

Data were analyzed using SPSS 20.0 (IBM Corporation, Armonk, NY) statistical software. To determine statistical significance, paired t-test analysis was performed for each dose parameter between groups, and P<0.05 was considered a statistically significant difference.

Results

Overall analysis

In this study, 80 treatment plans were generated for 20 patients, 20 each for Co-CRIM-E, IMRT-E, Co-CRIM-T, and IMRT-T plans. Every plan was reviewed by the radiation oncologist and considered to meet the clinical constraints. The differences between Co-CRIM-E and IMRT-E plans, as well as the differences between Co-CRIM-T and IMRT-T plans were compared. Figure 1 showed the differences in dose distribution between the two plans in the same cross-section of the same patient, and Figure 2 showed the differences in dose volume histogram (DVH) between the Co-CRIM and IMRT plans for the same patient as in Figure 1.

Figure 1 The differences in dose distribution between the four plans. (A) Co-CRIM-E plan which was designed based on Co-CRIM, and delivered with Varian Edge. (B) IMRT-E plan which was designed based on IMRT, and delivered with Varian Edge. (C) Co-CRIM-T plan which was designed based on Co-CRIM, and delivered with Varian TrueBeam. (D) IMRT-T plan which was designed based on IMRT, and delivered with Varian TrueBeam) in the same cross-section of the same patient. Co-CRIM, conformal radiotherapy-intensity modulated radiotherapy-combined and intensity-modulated radiotherapy; Co-CRIM-E, plans designed based on Co-CRIM and delivered with Varian Edge; Co-CRIM-T, plans designed based on Co-CRIM and delivered with TrueBeam; IMRT, intensity modulated radiotherapy; IMRT-E, plans designed based on IMRT and delivered with Varian Edge; IMRT-T, plans designed based on IMRT and delivered with Varian TrueBeam.

Figure 2 The differences in DVH between the Co-CRIM (the solid line) and IMRT (the dotted line) plans. (A) Plan delivered with Varian Edge. (B) Plan delivered with Varian TrueBeam for the same patient. Blue represents PTV, purple represents ITV, skin color represents Heart, black represents Spinal cord, slateblue represents Esophagus, lightblue represents Rib, maroon represents Trachea, orange represents Total Lung, forest represents Brachial plexus. Co-CRIM, conformal radiotherapy-intensity modulated radiotherapy-combined and intensity-modulated radiotherapy; DVH, dose volume histogram; IMRT, intensity modulated radiotherapy; ITV, internal target volume; PTV, planning target volume.

PTV differences between the two plans

Table 3 showed the data for each dosimetric parameter of PTV in both plans. CI of Co-CRIM-E plans was 1.02±0.09, R50 was 4.85±0.86, and D2cm was 31.14±2.05 Gy, which were slightly higher than those of IMRT-E plans. Although the differences were statistically significant, the differences in absolute values were small. Dmax/Dp was significantly lower in Co-CRIM-E plans than that in IMRT-E plans (P<0.05). This was also the same when comparing Co-CRIM-T plans with IMRT-T plans.

OARs differences between the two plans

The dosimetric parameters of total lung, heart, spinal Cord, esophagus, brachial plexus, trachea and large bronchus and rib in both plans were showed in Table 4. The results revealed that MLD, V10, V12.5, V13.5 and V20 of total lung were slightly higher in Co-CRIM-E plans than those in IMRT-E plans (P<0.05). MLD, V10, V12.5, V13.5 and V20 of total lung were also slightly higher in Co-CRIM-T plans than that in IMRT-T plans (P<0.05). No statistical differences were in the remaining parameters (P>0.05).

Differences in complexity and delivery accuracy of the two plans

Table 5 showed MU, MF, γ and average segment number for different plans. MU, MF and average segment number for Co-CRIM-E and Co-CRIM-T plans were significantly lower than those for IMRT-E and IMRT-T plans, respectively (P<0.001). MF was reduced by (12.25±6.23)% with the Co-CRIM method when plans were delivered by Varian Edge accelerator. Based on Varian TrueBeam accelerator, MF was reduced by (11.54±5.44)% using the Co-CRIM method. For γ, Co-CRIM-E plans were significantly higher than IMRT-E plans (P=0.04), and Co-CRIM-T plans were also significantly higher than IMRT-T plans (P=0.03).

Discussion

In this study, the clinical feasibility of the Co-CRIM method in central lung cancer patients treated with SBRT was evaluated by analyzing data on dosimetric parameters and delivery accuracy of Co-CRIM. The results showed that for central lung cancer SBRT, the Co-CRIM approach significantly reduced plan complexity and improved dose delivery consistency with slightly reduced target conformability compared to IMRT. The results provided data to support the clinical feasibility of the Co-CRIM planning strategy and showed that the method can be applied to different accelerator, validating the generalizability of the method.

SBRT has become one of the standard treatments for early-stage NSCLC patients who is unable to undergo or refuses surgery, as well as for patients with oligometastases (26-28). 3DCRT and IMRT are the commonly used methods for designing SBRT plans. It is well known that CRT plans are less complex and have better consistency in planned and delivered dose, and IMRT plans have advantages in sufficient irradiation of target and adequate protection or OARs. Therefore, in a previous study (23), a Co-CRIM strategy combining the advantages of CRT and IMRT was proposed. Its clinical feasibility in peripheral lung cancer has been validated, and it was found that planning complexity was effectively reduced and the γ passing rate was improved by Co-CRIM with the dosimetric advantages of IMRT. As the toxicity of radiotherapy has been studied, central lesions, which are known as “no-fly zones”, are increasingly treated with SBRT (29,30). Compared with peripheral lung cancer, central lung cancer has a unique target location adjacent to critical OARs including trachea and esophagus, which leads to an increasing of the risk of OARs irradiation. Radiotherapy planning for such cases requires strict constraints of OAR doses while maintaining sufficient target coverage, posing a greater challenge in balancing these two objectives. This results in higher technical demands for plan optimization, longer planning time, and markedly increased overall planning complexity. To date, the clinical feasibility of the Co-CRIM technique has only been validated in peripheral lung cancer (23), whereas its applicability to the more challenging central lung cancer remains unexplored. Following a stepwise research process from simple to complex, the present study applied this technique to patients with central lung cancer to further verify its clinical feasibility and provide reliable evidence for its subsequent clinical translation. Furthermore, given the large population and high patient volume in China, Co-CRIM exhibits higher treatment efficiency and lower machine wear compared with IMRT, making it more suitable for the practical demands of clinical practice in China.

Compared with the IMRT method, the difference of the Co-CRIM method lies in the setting of the maximum number of segments, the minimum segment area and the minimum segment MUs. The method does not increase the number of segments. The method achieved a significant reduction in planning complexity without adding additional design time to the planner. Therefore, the application of the Co-CRIM method to clinical practice does not change the design process of treatment plans, causing inconvenience to the planner.

By analyzing the comparative results of each dosimetric parameters of PTV across different plans, it can be found that the conformability of target and the dose fall-off gradient of the Co-CRIM method were slightly inferior to those of IMRT method. The reason for this was analyzed as follows. In the design of inverse planning, more subfields can better modulate the subfield area and MLC position, thereby achieving superior target conformability and steeper dose fall-off gradient. In contrast, the Co-CRIM method only had one subfield per field, whereas IMRT method typically include multiple subfields per field. This fundamental difference in subfield number may account for the slightly inferiority of Co-CRIM relative to IMRT in terms of target conformality and dose fall-off gradient. Higher modulation brought problems such as small subfield area and complex MLC position, which may lead to inaccurate dose delivery. In addition, the target conformability and dose fall-off gradient of Co-CRIM method were slightly worse than IMRT, but they all met the clinical constraints. Notably, the highest dose within the target of IMRT method was significantly higher than that of Co-CRIM method. Therefore, the highest dose within the target and its location should be reviewed carefully when using IMRT method to design SBRT treatment plan for central lung cancer patients to avoid causing damage to OARs.

Comparing the dosimetric parameters of OARs, it can be seen that there is no statistical difference in all indicators except for total lung. For total lung metrics, those of Co-CRIM were slightly higher than those of IMRT, but the absolute differences were small. This could be attributed to the steeper dose fall-off gradient of IMRT, which results in a slightly lower dose to the total lung surrounding the target. In addition, in previous study (23) of peripheral lung cancer, there were no differences in dosimetric parameters for total lung, heart and spinal cord between Co-CRIM and IMRT techniques. In contrast, there were differences in dosimetric parameters for total lung in the present study, which may be due to the increased complexity of the plan for central lung cancer.

Plan complexity and delivery accuracy are critical factors in radiation therapy. While high plan complexity can yield superior dose distributions, it may lead to issues such as compromised MLC delivery accuracy. Furthermore, highly complex plans often entail extended treatment times, which decrease patient comfort, particularly for those unable to maintain stable immobility for extended periods. Delivery accuracy is crucial for radiation therapy, and the actual dose received by the patient in clinical practice is a primary concern for the radiation oncologist. Even with an optimal planned dose distribution, a high degree of error during delivery would defeat the original purpose of radiation therapy and may compromise the patient’s treatment outcomes. This study demonstrated that Co-CRIM has absolute advantages in planning complexity and delivery accuracy. It may be a good choice for patients with physical discomfort to adopt Co-CRIM to design SBRT plans for central lung cancer patients.

This study included both Varian Edge and TrueBeam linear accelerators, with the primary objective of systematically evaluating the clinical generalizability of the Co‑CRIM technique across different radiotherapy platforms, thereby avoiding bias caused by restricting results to a single device. Although Edge and TrueBeam linear accelerators are both manufactured by Varian, they possess inherent differences in MLC transmission dose. The MLC transmission of Edge is generally lower than that of TrueBeam, which may influence low‑dose spill for small targets or highly modulated fields. To effectively account for such inherent hardware differences, a “within‑device comparative design” was employed, in which dosimetric comparisons between Co‑CRIM and IMRT plans were performed separately and independently on Edge and TrueBeam linear accelerators. This approach minimized confounding from systematic inter‑machine variations and ensured the objectivity of the comparative results. Furthermore, validating the performance of Co‑CRIM on two distinct accelerators allowed us to clearly define its device compatibility and confirm that its therapeutic benefits were not machine‑dependent but reflected true clinical generalizability. These findings therefore provide more comprehensive and reliable evidence to support the broader clinical implementation of the Co‑CRIM technique.

There are also some limitations in this study. First, as a retrospective study, its inherent design may introduce patient selection bias, and a prospective investigation may better validate the results. Second, the study cohort was heterogeneous in terms of tumor location and degree of centrality. Stratified analyses according to tumor location and centrality classification may yield more precise results, which is the direction of our next study. Finally, given that ultra-central lung cancer is adjacent to critical OARs and associated with substantially elevated treatment risk, our institution adopts conventionally fractionated IMRT for such patients, and no corresponding SBRT cases are available for analysis.

Conclusions

This study investigated the clinical feasibility of Co-CRIM approach previously proposed by our team in central lung cancer patients treated with SBRT. Compared with the IMRT method, this method significantly improved the plan complexity and delivery accuracy with slightly reduced target conformability. The results of this study provided a basis for the clinical use of this method in central lung cancer patients treated with SBRT, and may also provide theoretical support for prospective clinical trials. The method was applicable to different accelerator and may be extended to different institution, thus having strong promotion potential.

Acknowledgments

The authors thank the National Natural Science Foundation of China for its financial support.

Footnote

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-aw-2310/dss

Funding: This work was supported by the National Natural Science Foundation of China (Nos. 82303947, 12305353, 12375346, 82203976 and 82403785), the Shanghai Municipal Health Commission Health Industry Clinical Research Special Project (No. 20244Y0035), and the Natural Science Foundation of Shanghai (No. 24ZR1464200).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-aw-2310/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Shanghai Chest Hospital (No. KS24052). Since it was a retrospective study, written informed consent was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Xie S, Wu Z, Qi Y, Wu B, Zhu X. The metastasizing mechanisms of lung cancer: Recent advances and therapeutic challenges. Biomed Pharmacother 2021;138:111450. [Crossref] [PubMed]
2. Wang R, Chai WS, Pan DZ, Shan LN, Shi X, He YH, Pan S. RIOK1 is associated with non-small cell lung cancer clinical characters and contributes to cancer progression. J Cancer 2022;13:1289-98. [Crossref] [PubMed]
3. Riely GJ, Wood DE, Ettinger DS, Aisner DL, Akerley W, Bauman JR, et al. Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2024;22:249-74. [Crossref] [PubMed]
4. Chan M, Wong M, Leung R, Cheung S, Blanck O. Optimizing the prescription isodose level in stereotactic volumetric-modulated arc radiotherapy of lung lesions as a potential for dose de-escalation. Radiat Oncol 2018;13:24. [Crossref] [PubMed]
5. Miura H, Ozawa S, Nagata Y. Efficacy of robust optimization plan with partial-arc VMAT for photon volumetric-modulated arc therapy: A phantom study. J Appl Clin Med Phys 2017;18:97-103. [Crossref] [PubMed]
6. Román A, Perez-Rozos A, Otero A, Jodar C, García-Ríos I, Lupiañez-Perez Y, Antonio Medina J, Gomez-Millan J. Efficacy and safety of a simplified SBRT regimen for central and peripheral lung tumours. Clin Transl Oncol 2020;22:144-50.
7. Ceniceros L, Aristu J, Castañón E, Rolfo C, Legaspi J, Olarte A, Valtueña G, Moreno M, Gil-Bazo I. Stereotactic body radiotherapy (SBRT) for the treatment of inoperable stage I non-small cell lung cancer patients. Clin Transl Oncol 2016;18:259-68. [Crossref] [PubMed]
8. Samper Ots PM, Vallejo Ocaña C, Martin Martin M, Celada Álvarez FJ, Farga Albiol D, Almendros Blanco P, et al. Stereotactic body radiotherapy for early-stage non-small cell lung cancer: a multicentre study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society). Clin Transl Oncol 2022;24:342-9. [Crossref] [PubMed]
9. Lalonde R, Abdelhakiem M, Keller A, Huq MS. Dosimetric parameters related to occurrence of distant metastases and regional nodal relapse after SBRT for early-stage non-small cell lung cancer. Radiother Oncol 2022;169:90-5. [Crossref] [PubMed]
10. Lo SS, Fakiris AJ, Chang EL, Mayr NA, Wang JZ, Papiez L, Teh BS, McGarry RC, Cardenes HR, Timmerman RD. Stereotactic body radiation therapy: a novel treatment modality. Nat Rev Clin Oncol 2010;7:44-54. Erratum in: Nat Rev Clin Oncol 2010;7:422.
11. Siva S, Bressel M, Mai T, Le H, Vinod S, de Silva H, et al. Single-Fraction vs Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases (SAFRON II): The Trans Tasman Radiation Oncology Group 13.01 Phase 2 Randomized Clinical Trial. JAMA Oncol 2021;7:1476-85. [Crossref] [PubMed]
12. Kim H, Vargo JA, Ling DC, Beriwal S, Smith KJ. Cost-Effectiveness Analysis of Upfront SBRT for Oligometastatic Stage IV Non-Small Cell Lung Cancer Based on Mutational Status. Am J Clin Oncol 2019;42:837-44. [Crossref] [PubMed]
13. Bezjak A, Paulus R, Gaspar LE, Timmerman RD, Straube WL, Ryan WF, et al. Safety and Efficacy of a Five-Fraction Stereotactic Body Radiotherapy Schedule for Centrally Located Non-Small-Cell Lung Cancer: NRG Oncology/RTOG 0813 Trial. J Clin Oncol 2019;37:1316-25. [Crossref] [PubMed]
14. Ahmed N, Hasan S, Schumacher L, Colonias A, Wegner RE. Stereotactic body radiotherapy for central lung tumors: Finding the balance between safety and efficacy in the "no fly" zone. Thorac Cancer 2018;9:1211-4. [Crossref] [PubMed]
15. Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, Fakiris A, Bezjak A, Videtic G, Johnstone D, Fowler J, Gore E, Choy H. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 2010;303:1070-6. [Crossref] [PubMed]
16. Korzets Ceder Y, Fenig E, Popvtzer A, Peled N, Kramer MR, Saute M, Bragilovsky D, Schochat T, Allen AM. Stereotactic body radiotherapy for central lung tumors, yes we can! Radiat Oncol 2018;13:77. [Crossref] [PubMed]
17. Gulstene S, Ruwanpura T, Palma D, Joseph N. Stereotactic Ablative Radiotherapy in the Treatment of Early-Stage Lung Cancer - A Done Deal? Clin Oncol (R Coll Radiol) 2022;34:733-40. [Crossref] [PubMed]
18. Senthi S, Haasbeek CJ, Slotman BJ, Senan S. Outcomes of stereotactic ablative radiotherapy for central lung tumours: a systematic review. Radiother Oncol 2013;106:276-82. Erratum in: Radiother Oncol 2013;109:183.
19. Palma D, Daly M, Urbanic J, Giuliani M. Stereotactic Radiation for Ultra-Central Lung Tumors: Good Idea, or Ultra-Risky? Int J Radiat Oncol Biol Phys 2019;103:788-91. [Crossref] [PubMed]
20. Zhao Y, Khawandanh E, Thomas S, Zhang S, Dunne EM, Liu M, Schellenberg D. Outcomes of stereotactic body radiotherapy 60 Gy in 8 fractions when prioritizing organs at risk for central and ultracentral lung tumors. Radiat Oncol 2020;15:61. [Crossref] [PubMed]
21. Liu H, Sintay B, Pearman K, Shang Q, Hayes L, Maurer J, Vanderstraeten C, Wiant D. A hybrid planning strategy for stereotactic body radiation therapy of early stage non-small-cell lung cancer. J Appl Clin Med Phys 2018;19:117-23. [Crossref] [PubMed]
22. Hamzeei M, Modiri A, Kazemzadeh N, Hagan A, Sawant A. Inverse-planned deliverable 4D-IMRT for lung SBRT. Med Phys 2018;45:5145-60. [Crossref] [PubMed]
23. Duan Y, Zhou L, Wang H, Chen H, Gu H, Shao Y, Feng A, Huang Y, Fu X, Yue NJ, Ma K, Kong Q, Xu Z. A novel CRT-IMRT-combined (Co-CRIM) planning technique for peripheral lung stereotactic body radiotherapy in pinnacle treatment planning system. J Appl Clin Med Phys 2021;22:97-107. [Crossref] [PubMed]
24. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 2007;147:573-7. [Crossref] [PubMed]
25. Timmerman R. A Story of Hypofractionation and the Table on the Wall. Int J Radiat Oncol Biol Phys 2022;112:4-21. [Crossref] [PubMed]
26. Amin SA, Alam M, Baine MJ, Meza JL, Bennion NR, Zhang C, Rahman I, Lin C. The impact of stereotactic body radiation therapy on the overall survival of patients diagnosed with early-stage non-small cell lung cancer. Radiother Oncol 2021;155:254-60. [Crossref] [PubMed]
27. Savanović M, Loi M, Rivin Del Campo E, Huguet F, Foulquier JN. Assessment of Organ Dose Reduction Using Dynamic Conformal Arc and Static Field with FFF Beams for SBRT in Lung Cancer. Cancer Invest 2022;40:868-78. [Crossref] [PubMed]
28. Li F, Jiang H, Bu M, Mu X, Zhao H. Dose-effect relationship of stereotactic body radiotherapy in non-small cell lung cancer patients. Radiat Oncol 2022;17:211. [Crossref] [PubMed]
29. Owen D, Sio TT. Stereotactic body radiotherapy (SBRT) for central and ultracentral node-negative lung tumors. J Thorac Dis 2020;12:7024-31. [Crossref] [PubMed]
30. Nguyen KNB, Hause DJ, Novak J, Monjazeb AM, Daly ME. Tumor Control and Toxicity after SBRT for Ultracentral, Central, and Paramediastinal Lung Tumors. Pract Radiat Oncol 2019;9:e196-e202. [Crossref] [PubMed]