Feasibility study of unflattened photon beam in the treatment of liver carcinoma using stereotactic body radiation therapy

Introduction

Liver carcinoma is the most common chance of metastases in human body in case of malignancies. Removal of such primary and metastatic liver tumors through surgical procedures is the standard care of treatment worldwide. However, most often these liver tumours are unresectable and hepatectomy or radiofrequency ablation processes are challenging. Improvements in chemotherapy drugs and targeted molecular agents have raised patient survival. In oligo-metastatic patients, radiation therapy may improve overall survival (1). But it is believed to have a limited role due to the risk of radiation-induced liver toxicities (2). Literature suggests that such liver toxicities may increase with mean radiation doses to healthy liver tissues (3). So, it is advised to treat smaller size liver targets with higher radiation doses, keeping the mean liver dose within tolerance (4). Radiation therapy has been used for palliation in liver tumours since long days (5).

However, advancements in imaging techniques and improvements in treatment planning and delivery with motion management facilitated the radiation oncology community to cure liver tumours with radiation therapy (6). It has resulted in the development of a treatment technique called ‘stereotactic body radiation therapy (SBRT)’, which has been reported to have high tumour response with local control rates for liver tumours with SBRT in many publications (7). Delivery of high fractional doses in limiting fractions and lesser dose spillage resulted in higher biologically effective dose to the target in SBRT (8).

Accuracy can be achieved at various levels, like immobilization in simulation process, calculation algorithms in planning process and motion management in delivery process. Simulation with ‘vacuum cushion bag’ increases patient comfort and setup reproducibility. As a routine practice, different scans are acquired to create projected images.

Also, the commercially available algorithms gave us freedom to find accurate dose distribution in homogeneous as well as heterogeneous media. Acuros XB (AXB) and anisotropic-analytical-algorithm (AAA) can predict the dose in the interface region accurately. Treatment delivery is an important step that decides the fate of all the previous processes. As the breathing of patients creates uncertainty in positioning of the liver, the outcome of SBRT treatment depends on the accurate localization of treating organ. Different methods like tumour tracking, internal marker matching, and restriction of motion may be used to increase the SBRT precision.

Patient as well as organ movement during the treatment may be reduced by increasing dose rate also. Flattening-filter-free (FFF) beams facilitate the planner to deliver the plan with a very high dose rate, as carousal removes the flattening filter from the beam path. It completes the whole treatment in significantly less time and reduces the intra-fraction movement. Munirathnam suggested the use of unflattened beams in breast cases (9). Reggiori et al. performed a similar study with flattening-filter-free beams and found that useful for intermediate-sized liver tumours with reduced treatment time (10). Such studies are not available in plenty of numbers which motivated us to perform this dosimetric comparison.

This study was designed to evaluate the feasibility of AXB and AAA calculation algorithms for liver cancer treatment with intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques using unflattened photon beam energies.

Methods

Patient selection and pre-treatment requisites

Thirty patients with a single liver tumour were selected for the study. These patients were found not suitable for surgical resection after discussion and were treated with SBRT in our institute. Pre-treatment evaluation consists of physical examination and laboratory tests, computed tomography (CT) (Siemens Shanghai Medical Equipment Ltd., Shanghai, China; model: SOMATOM go.Sim) scans of thorax and abdomen with intravenous contrast and positron emission tomography (PET) CT (Wipro GE Healthcare Private Limited, Milwaukee WI, USA; model: Discovery MI-128 Slice) scan with administration of F-18 fluoro-deoxy-glucose (FDG) for better target localization. Right-sided single lesion was included in the study and the patients with multiple lesions were excluded from this. All the tumours were lying in the periphery only.

SBRT planning

CT scan of the patients was acquired in supine position using a ‘vacuum cushion bag’ immobilization device. Radio-opaque fiducials were used to mark the reference slice position. Respiratory scans were acquired with external breathing tracker marker (tracked with infrared camera and captured in rpm gating system) and slice thickness was kept at 1 mm. Delineation of tumour target and organs-at-risk (OARs) was completed by a radiation oncologist (Figure 1).

Figure 1 Delineation of contours. (A) Structures delineated; (B) axial view; (C) 3D view; (D) coronal view; (E) sagittal view. 3D, three-dimensional; CT, computed tomography; GTV, gross tumor volume; LT, left; NS, normal tissue; PTV, planning target volume; RT, right.

Isocentric plans were generated for the prescription dose 40 Gy in 5 fractions to planning target volume (PTV) using two different planning techniques, i.e., IMRT and VMAT by a medical physicist (Figure 2). Plans were optimized in such a way that the following constraints will be achieved, as shown in Table 1.

Figure 2 Field placement in intensity modulated radiation therapy (A) and volumetric modulated arc therapy (B).

IMRT uses static gantry angles with a sliding-window technique where multi-leaf collimator (MLC) changes the leaf position during radiation exposure. However, in VMAT technique, gantry rotates with radiation delivery in addition to MLC position and dose rate. Intensity modulated plans are generated by inverse planning techniques where a dedicated treatment planning system (TPS) optimizes the deliverable plan with change in beam fluence of each beamlet. The system calculates the optimized plan with available calculation algorithms and a final solution is received for tumor target problem.

A few calculation algorithms are commercially available that the planner utilizes for achieving the optimized plans, like pencil beam convolution (PBC) algorithm, analytic anisotropic algorithm (AAA), collapse cone convolution (CCC) algorithm, AXB algorithm and Monte-Carlo (MC) algorithm.

Plans were generated using Eclipse TPS (Varian Medical Systems, Palo Alto, USA; Version 15.6) and were delivered on TrueBeam STX linear accelerator (Linac) (Varian Medical Systems; Version 2.1).

TrueBeam STX linac is equipped with a high-definition multi-leaf collimator (HDMLC) and FFF beam. The machine can deliver the treatment with a high dose rate of 1,400 MU/min for 6FFF and 2,400 MU/min for 10FFF photon beam. This helps in minimizing the intra-fraction motion while delivering the high-dose treatment. SBRT was delivered either by using multiple coplanar static beams or by conformal arcs.

Dose reporting and evaluation

Planning gross tumour volume (PGTV) coverage was evaluated for D_98%, D_95%, D_50%, D_5%, D_2% which signifies the dose receiving 98%, 95%, 50%, 5% & 2% of PTV volume and mean dose (D_mean) received by PGTV.

It is strictly important in stereotactic radiosurgery (SRS)/stereotactic radiotherapy (SRT) and SBRT to deliver the radiation dose precisely with conformal dose to target volume and a lesser dose to surrounding normal structures. The conformity index (CI) shows the conformal coverage of prescribed dose around the target (11). Ideally, it should be less than 1.2 for fractionated high-dose therapy. The conformity of the dose to PGTV was evaluated as ratio of volume of prescription isodose curve and total volume of PGTV, i.e.,

CI=Volumeofprescribeddose(cm3)PGTVvolume(cm3)<1.2[1]

Homogeneity index (HI) quantifies the uniform distribution of prescription dose within the target (12). It should approach zero in ideal plans and can be noticed with a sudden fall of the dose-volume histogram for PGTV (13). The HI was also evaluated using the ratio of the difference of D_2% & D_98% and D_50% of the PGTV, i.e.,

HI=D2%−D98%D50%[2]

The gradient index (GI) is a measure of the dose fall of the prescribed dose from target boundaries, away from the target volume (14). GI can be quantified as,

GI=Volumeof50%isodosecurveVolumeof100%isodosecurve[3]

There is no empirical formula to relate GI with OARs doses, but decreased GI may result in lesser doses to nearby healthy organs (15). Hence, the lower value of GI may indicate the lower treatment-related complications for the patients.

Modulation index (MI) is one of the important plan evaluation indices to quantify the modulation of plan parameters (16). This analyses the variation of MLC motion, gantry rotation and dose rate. It was calculated using the formula, i.e.,

MI=DoseprescribedNo.ofMUrequiredintechnique[4]

The conformity number (CN) is the product of a tumor coverage factor and a normal tissue over dosage factor (17). It can be represented as,

CN=TVRI2TV×VRI[5]

where TV_RI= target volume covered by 98% isodose curve; V_RI= volume of reference isodose, i.e., 98%.

To restrict the dose spillage, the following parameters were evaluated in terms of ‘High dose spillage’ and ‘Intermediate dose spillage’ (18). The parameters were represented as:

• High dose spillage = volume of all tissue outside PTV receiving dose of 105% of the prescription dose <15% of PTV volume (cc) (19);
• Intermediate spillage: D_2cm: the maximum dose to any point 2 cm, or more away from PTV in any direction <66% of the prescription dose (20,21).

  $$R_{50\%}=\frac{Volumeof50\%isodose\left(c{m}^3\right)}{PTVvolume\left(c{m}^3\right)}<3.5$$[6]

Statistical analysis

All the patient population was included in the statistical analysis. Statistical Package for Social Science (SPSS Inc., Chicago, IL, China) V.20 was used for statistical analysis. A paired t-test (two-sided paired-sample t-test) was performed to find the significance of the data (22). Population data (more than or equal to 30) satisfied the normality criteria. The results were considered statistically significant when P≤0.05.

Quality assurance (QA) analysis

ArcCHECK Phantom (Model 1220, Sun Nuclear, Melbourne, FL, USA) was used to analyze the patient treatment plans (23). It is a cylindrical water-equivalent phantom with a three-dimensional array of 1,386 diode detectors, arranged in a spiral pattern, with 10 mm sensor spacing. The center of the phantom (15 cm diameter) is designed to accommodate various accessories such as a solid homogeneous core, a dosimetric core with ion chamber(s) or diode arrays, an imaging QA core, a core with heterogeneous materials for dose studies, etc. (24). The ArcCHECK also features two inclinometers to measure the angle of rotation about the cylinder axis and to measure the tilt of the axis. A temperature sensor measures the ambient temperature of the detector area. Dose measurements from each sensor are updated every 50 ms. ArcCHECK facilitates the user to validate the plans generated with flattened as well as unflattened photon beam (25). QA plans were recalculated on Phantom for both algorithms. Phantom was exposed to treatment plans of 5 randomly selected patients and the results were compared with the TPS calculated plans.

Ethical approval

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. It is a retrospective study, and no experiment was carried out on either human or animal. Hence Ethics approval is not required.

Results

Target volume coverage

The average target volume was 122.82±126.58 cm³. The isocentric plans were generated for IMRT and VMAT techniques using 6MV, 6FFF and 10FFF photon energies with AAA and AXB calculation algorithms as shown in Table 2. Plans were clinically acceptable and hence, there was no significant difference in D_95% dose coverage parameter (Figures 3-5).

Figure 3 Axial view of coverage of prescription dose and spillage. (A) IM_AAA_6X; (B) IM_AXB_6X; (C) IM_AAA_6FFF; (D) IM_AXB_6FFF; (E) IM_AAA_10FFF; (F) IM_AXB_10FFF; (G) VM_AAA_6X; (H) VM_AXB_6X; (I) VM_AAA_6FFF; (J) VM_AXB_6FFF; (K) VM_AAA_10FFF; (L) VM_AXB_10FFF. Prescription dose 100% shown in red colour and spill of 50% dose shown in blue colour. Definitions of the plans are in Appendix 1.

Figure 4 Coronal view of coverage of prescription dose and spillage. (A) IM_AAA_6X; (B) IM_AXB_6X; (C) IM_AAA_6FFF; (D) IM_AXB_6FFF; (E) IM_AAA_10FFF; (F) IM_AXB_10FFF; (G) VM_AAA_6X; (H) VM_AXB_6X; (I) VM_AAA_6FFF; (J) VM_AXB_6FFF; (K) VM_AAA_10FFF; (L) VM_AXB_10FFF. Prescription dose 100% shown in red colour and spill of 50% dose shown in blue colour. Definitions of the plans are in Appendix 1.

Figure 5 Sagittal view of coverage of prescription dose and spillage. (A) IM_AAA_6X; (B) IM_AXB_6X; (C) IM_AAA_6FFF; (D) IM_AXB_6FFF; (E) IM_AAA_10FFF; (F) IM_AXB_10FFF; (G) VM_AAA_6X; (H) VM_AXB_6X; (I) VM_AAA_6FFF; (J) VM_AXB_6FFF; (K) VM_AAA_10FFF; (L) VM_AXB_10FFF. Prescription dose 100% shown in red colour and spill of 50% dose shown in blue colour. Definitions of the plans are in Appendix 1.

However, a significant difference was reported after selecting AXB and unflattened photon energies. Similar results were observed for D_50%, D_5% and D_2% as shown in Table 3. CI was not significant for IMRT plans but a significant difference was observed for VMAT technique. HI and R50 were also found significantly different for all the energies and modalities except in IMRT 6FFF. The GI has also shown a similar pattern. MI was significantly different for IMRT technique with different energies but not for VMAT modality as shown in Table 4. CN has not shown any significant difference except for AXB algorithm in IMRT (Figure 6).

Figure 6 Graphical representation of results for tumour target. (A) Target coverage of 98% prescription dose, i.e., D₉₈; (B) representation of 2% of prescription dose to tumour target, i.e., D₂; (C) representation of 50% of prescription dose to tumour target, i.e., D₅₀; (D) homogeneity index; (E) conformity index; (F) modulation index. CI, conformity index; HI, homogeneity index; MI, modulation index. Definitions of the plans are in Appendix 1.

OAR

Ribs, duodenum and heart

Doses evaluated for the contoured structures, i.e., ribs, duodenum and heart were within the acceptable limits. Maximum dose received by Ribs were significantly different for all the energies and modalities except for IMRT AXB. Similarly, the volume of ribs receiving 35 Gy dose was significantly different for VMAT AXB. There was no significant difference observed for the maximum dose received by duodenum as well as heart as shown in Table 5. Similarly, the volume of duodenum receiving 12.5 Gy dose was significantly different for AAA 6FFF in IMRT technique as shown in Table 6.

Normal liver (liver-PTV)

Volume of normal liver (excluding from PTV) receiving 21 Gy dose was evaluated and there was no significant difference observed except for 10FFF (Figure 7). However, mean dose D_mean of normal liver was found significantly different for 6FFF photon beam as shown in Table 7.

Figure 7 Graphical representation of results for OARs. (A) Ribs D_max; (B) liver-PTV V_{21 Gy}; (C) heart D_max; (D) stomach D_max; (E) spinal cord D_max; (F) skin D_max. Definitions of the plans are in Appendix 1. D_max, maximum dose received by structure; V_{D Gy}, volume of structure receiving dose ‘D’ Gy; OAR, organ-at-risk; PTV, planning target volume.

Stomach, bilateral kidneys and spinal cord

Maximum dose received by stomach was significantly different for VMAT technique. However, no significant difference was reported for V18 (volume of stomach receiving 18 Gy dose), V30 (volume of stomach receiving 30 Gy dose) and D_100% (dose received by full organ). Although VMAT AXB_6MV has shown a significant difference when compared with IMRT AAA_6MV. No significant difference was observed for the doses received by bilateral kidneys. However, mean dose to right kidney was reported significantly different for IMRT using 10FFF beam. Maximum dose to spinal cord was significantly different for VMAT cases. No difference was reported for V23 (volume of spinal cord receiving 23 Gy). Also, V14.5 (volume of spinal cord receiving 14.5 Gy) was evaluated, and no significant difference was observed except for VMAT AXB_6MV, 6FFF and VMAT AAA 10FFF as shown in Table 7.

Skin, bowel and healthy body tissues (body-PTV)

Dose maximum to skin was found significantly different for all the energies and modalities except VMAT AXB_6MV, 6FFF and VMAT AAA 6FFF. No significant difference was observed for bowel doses V40 (volume of bowel receiving 40 Gy) and V35 (volume of bowel receiving 35 Gy). Mean dose to healthy body tissues was reported significantly different in IMRT and VMAT with all the energies except for IMRT AAA 6FFF and IMRT AAA 10FFF as shown in Tables 8,9.

Dose spillage, integral dose and total monitor units (TMU)

Intermediate spillage was evaluated using maximum dose to ring of 2 cm radius around the PGTV, i.e., D_{max(2 cm)} and found a significant difference in the data except for IMRT AXB_6MV. High dose spillage was reported not significant except for IMRT AXB_6MV and IMRT AXB 6FFF which was a global dose maximum of more than 105% of the prescribed dose. Similarly, normal tissue integral dose (NTID) was statistically different for all the cases except IMRT AXB_6MV & 6FFF. TMUs were reported significantly different for IMRT cases but remained insignificant for VMAT technique with all the selected photon energies as shown in Table 8.

QA analysis

The QA plans were compared with measured treatment plans (Figures 8,9) and results were tabulated for analysis as shown in Table 10.

Figure 8 ArcCHECK phantom and analysis software. (A) Array of diodes on surface for fluence measurement; (B) inclinometers for surface levelling and angular correction; (C) cavity in the middle for point dose measurement; and (D) software for analysis of QA plans. QA, quality assurance.

Figure 9 Graphical representation of ArcCHECK point doses for different criteria. Definitions of the plans are in Appendix 1.

Discussion

A non-invasive approach in SBRT offers the opportunity of delivering standardized high dose treatment in addition to routine drug treatment (26). Liver is a common site of metastases for most of the malignant cases and there are chances of its primary site also (27). Surgery and chemotherapy as a combination are considered as standard care of treatment. However, radiotherapy gives a strong alternative for those patients who are not fit for surgical procedures (28).

In the initial days, radiotherapy for such tumours was not considered a safe and reliable option. But due to advancement of imaging and planning techniques, it is possible to deliver the high prescribed dose with accuracy and motion management which leads to giving curative dose to target tumour and minimized dose to nearby healthy organs and tissues (29).

Although tumour motion remains the challenge but can be assessed using four-dimensional (4D) CT scan and internal target volume (ITV) can be drawn on this basis yet there are chances that healthy tissues may get irradiated (30).

Another challenge in treating liver carcinoma is the risk of radiation induced secondary cancers which is proportional to the mean radiation dose, received by healthy tissues (31). This is another reason which limits the patient population by treating SBRT due to the tumour size.

Herfarth et al. demonstrated the efficacy of SBRT in treating liver metastases using single fraction with local control rate of 66% at 18 months whereas Katz et al. reported the same with multi fraction with local control rate of 76% at 10 months and 57% at 24 months (32,33).

Andratschke et al. shared their findings where liver metastatic patients were treated with 5–12.5 Gy per fraction in 3–5 fractions. The local control rate was 74.7% at 12 months, 48.3% at 24 months and 48.3% at 36 months. They also reported that 100% local control can be achieved when minimum biologically equivalent dose (BED) to gross tumour is more than 120 Gy (34). Rubio et al. reported that the overall survival reached a medial time of 62 months, with estimated survival at 5 years of 57.6% using SBRT (35).

Data suggested that dose volume histogram (DVH) was improved for PGTV using unflattened photon beam energies for treatment planning and AXB algorithm for final calculation. This might be due to the forward scattering nature of unflattened beam and contribution of lateral scattering for AXB calculation algorithm (36). Conformity was better with VMAT planning when compared to IMRT. It might be possible due to the nature of delivery of beams. VMAT delivers the dose with continuous changing dose rate, MLC positions and gantry rotation. It is unlike the IMRT plans where gantry stops to treat the patient (37). HI and R50 have not shown much deviation between the base level and IMRT AAA 6FFF as the D_max for both the beams is nearer and they deposited the same dose homogeneously. GI has followed a similar pattern due to the same reason. MI has marked a significant difference in IMRT plans as total required monitor units were larger for static plans as compared with volumetric arcs. Static gantry rotation reduces the possible degrees of freedom for beamlets to travel and to deposit the dose. However, CN has shown a significant increase in case of AXB algorithm with IMRT technique as the AXB algorithm incorporates the lateral contributions of dose in in-homogeneity medium also (38).

Dose to OARs like ribs, duodenum and heart were within the tolerance as the dose spillage was confined to small volume around the site. Maximum doses to ribs were significantly reduced with VMAT plans due to its delivery technique. Dose volume of 21 Gy received by normal liver other than tumor target was drastically reduced with 10FFF photon beam energy which may be caused by its penetration power. At the same time, the mean dose of healthy liver tissues was significantly reduced with 6FFF unflatten beam which may be due to equal distribution of dose within the target. Maximum dose to stomach was significantly reduced with VMAT treatment technique as this delivers the dose in rotational manner which helps to reduce the tail of DVH for tumor target. Other doses were also reduced with VMAT plans calculated with AXB calculation algorithm due to its characteristics of delivering dose in the non-homogeneous medium. Doses to both the kidneys were well below the acceptable limits due to their separation from the target. Dose maxima for the spinal cord were significantly reduced with VMAT planning due to more concave shape of dose deposition (39).

Bowel doses were within tolerance due to their separation from the target volume. Dose to ring at 2 cm from the target boundary was also improved with arc technique. High dose spillage maximum was raised with AXB algorithm as this provides the dose to near boundary of target which may radiate the adjacent normal healthy body tissues. This may cause the increased NTID for those regions. In a similar manner, TMUs required to deliver the prescribed dose were more with IMRT treatment technique due to its non-rotational behaviour (40). However, VMAT utilized the almost similar TMU compared with IMRT AAA_6X plans. FFF photon beams have advantages of higher clinical dose rate which reduces the intra-fraction motion during the execution of treatment plan (41). ArcCHECK showed an edge for VMAT plans using AXB algorithm and 6FFF MV beam with a mean gamma passing rate of 98.9% for 3% dose difference (DD) and 3 mm distance-to-agreement (DTA) (42,43). This study elaborates the use of FFF photon beams in liver lesions and effectiveness of AAA and AXB algorithms in the treatment planning with the help of QA protocol which validated the accuracy of deliverable plans.

Limitations

This study included a sufficient number of patients to evaluate the efficacy of calculation algorithms and treatment techniques while treating liver cancers with advanced modalities. However, a greater number of patients need to be enrolled to find a standard solution. More such studies may be helpful to generalize the practices in the clinics.

Conclusions

The study concluded that SBRT treatment planned with VMAT using AXB algorithm and FFF beam is an efficient way to treat primary liver cancers. SBRT delivers the prescribed dose with strict evaluation criteria to save nearby healthy tissues. This provides the high therapeutic index with image-guided patient setup which might be superior to other available treatments. AXB algorithm is comparable with AAA calculation algorithm and may be useful for inhomogeneity medium. VMAT remains the choice of treatment as standard care of practice in such cases with unflattened photon beams for reproducible patient setup to minimize the treatment uncertainties.

Acknowledgments

The authors would like to thank the management of Rajiv Gandhi Cancer Institute and Research Centre, New Delhi for their continuous support and motivation to carry out this study. The contents in this manuscript are solely the responsibility of the authors and are not necessarily endorsed by AERB.

Footnote

Data Sharing Statement: Available at https://tro.amegroups.com/article/view/10.21037/tro-25-22/dss

Peer Review File: Available at https://tro.amegroups.com/article/view/10.21037/tro-25-22/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tro.amegroups.com/article/view/10.21037/tro-25-22/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. It is a retrospective study, and no experiment was carried out on either human or animal. Hence Ethics approval is not required.

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. Corbin KS, Hellman S, Weichselbaum RR. Extracranial oligometastases: a subset of metastases curable with stereotactic radiotherapy. J Clin Oncol 2013;31:1384-90. [Crossref] [PubMed]
2. Dawson LA, Normolle D, Balter JM, et al. Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 2002;53:810-21. Erratum in: Int J Radiat Oncol Biol Phys 2002;53:1422. [Crossref] [PubMed]
3. Pan CC, Kavanagh BD, Dawson LA, et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys 2010;76:S94-100. [Crossref] [PubMed]
4. Schefter TE, Kavanagh BD, Timmerman RD, et al. A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases. Int J Radiat Oncol Biol Phys 2005;62:1371-8. [Crossref] [PubMed]
5. Lausch A, Sinclair K, Lock M, et al. Determination and comparison of radiotherapy dose responses for hepatocellular carcinoma and metastatic colorectal liver tumours. Br J Radiol 2013;86:20130147. [Crossref] [PubMed]
6. Sanuki N, Takeda A, Kunieda E. Role of stereotactic body radiation therapy for hepatocellular carcinoma. World J Gastroenterol 2014;20:3100-11. [Crossref] [PubMed]
7. de Baere T, Tselikas L, Yevich S, et al. The role of image-guided therapy in the management of colorectal cancer metastatic disease. Eur J Cancer 2017;75:231-42. [Crossref] [PubMed]
8. Potters L, Steinberg M, Rose C, et al. American Society of Therapeutic Radiology and Oncology and American College of Radiology practice guidelines for the performance of stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys 2004;60:1026-32. [Crossref] [PubMed]
9. Munirathinam N, Pawaskar PN. Dosimetric comparison of flattened and flattening filter-free beams for liver stereotactic body irradiation in deep inspiration breath hold, and free breathing conditions. Journal of Radiotherapy in Practice. 2019;18:169-74.
10. Reggiori G, Mancosu P, Castiglioni S, et al. Can volumetric modulated arc therapy with flattening filter free beams play a role in stereotactic body radiotherapy for liver lesions? A volume-based analysis. Med Phys 2012;39:1112-8. [Crossref] [PubMed]
11. Feuvret L, Noël G, Mazeron JJ, et al. Conformity index: a review. Int J Radiat Oncol Biol Phys 2006;64:333-42. [Crossref] [PubMed]
12. Bhushan M, Tripathi D, Yadav G, et al. Effect of contrast medium on treatment modalities planned with different photon beam energies: a planning study. Rep Pract Oncol Radiother 2021;26:688-711. [Crossref] [PubMed]
13. Bhushan M, Yadav G, Tripathi D, et al. Dosimetric Analysis of Unflattened (FFFB) and Flattened (FB) Photon Beam Energy for Gastric Cancers Using IMRT and VMAT-a Comparative Study. J Gastrointest Cancer 2019;50:408-19. [Crossref] [PubMed]
14. Wagner TH, Bova FJ, Friedman WA, et al. A simple and reliable index for scoring rival stereotactic radiosurgery plans. Int J Radiat Oncol Biol Phys 2003;57:1141-9. [Crossref] [PubMed]
15. Reynolds TA, Jensen AR, Bellairs EE, et al. Dose Gradient Index for Stereotactic Radiosurgery/Radiation Therapy. Int J Radiat Oncol Biol Phys 2020;106:604-11. [Crossref] [PubMed]
16. Park JM, Park SY, Kim H, et al. Modulation indices for volumetric modulated arc therapy. Phys Med Biol 2014;59:7315-40. [Crossref] [PubMed]
17. van’t Riet A, Mak AC, Moerland MA, et al. A conformation number to quantify the degree of conformality in brachytherapy and external beam irradiation: application to the prostate. Int J Radiat Oncol Biol Phys 1997;37:731-6. [Crossref] [PubMed]
18. Fitzgerald R, Owen R, Barry T, et al. The effect of beam arrangements and the impact of non-coplanar beams on the treatment planning of stereotactic ablative radiation therapy for early stage lung cancer. J Med Radiat Sci 2016;63:31-40. [Crossref] [PubMed]
19. RTOG Trial 0813 Report. Available online: https://pps4rt.com/wp-content/uploads/2019/07/RTOG-0813-1.pdf
20. Pokhrel D, Badkul R, Jiang H, et al. Technical Note: Dosimetric evaluation of Monte Carlo algorithm in iPlan for stereotactic ablative body radiotherapy (SABR) for lung cancer patients using RTOG 0813 parameters. J Appl Clin Med Phys 2015;16:5058. [Crossref] [PubMed]
21. Bhushan M, Tripathi D, Kumar L, et al. Can a Low-energy Photon Beam Be Suitable for the Treatment of Cervical Malignancies? A Dosimetric Analysis. J Curr Oncol 2020;3:55-61.
22. Kumar G, Bhushan M, Kumar L, et al. Dosimetric Evaluation of Low-Dose Spillage Volumes for Head and Neck Cancer Using Intensity-Modulated Radiation Therapy and Volumetric Modulated Arc Therapy Treatment Techniques. Prog Med Phys 2021;32:70-81.
23. Thiyagarajan R, Nambiraj A, Sinha SN, et al. Analyzing the performance of ArcCHECK diode array detector for VMAT plan. Rep Pract Oncol Radiother 2016;21:50-6. [Crossref] [PubMed]
24. Kumar L, Yadav G, Kishore V, et al. Validation of the RapidArc Delivery System Using a Volumetric Phantom as Per Task Group Report 119 of the American Association of Physicists in Medicine. J Med Phys 2019;44:126-34. [Crossref] [PubMed]
25. Adamczyk M, Kruszyna-Mochalska M, Rucińska A, et al. Software simulation of tumour motion dose effects during flattened and unflattened ITV-based VMAT lung SBRT. Rep Pract Oncol Radiother 2020;25:684-91. [Crossref] [PubMed]
26. Timmerman RD, Herman J, Cho LC. Emergence of stereotactic body radiation therapy and its impact on current and future clinical practice. J Clin Oncol 2014;32:2847-54. [Crossref] [PubMed]
27. Griscom JT, Wolf PS. Liver Metastasis. Treasure Island (FL): StatPearls Publishing; 2024.
28. Gosalia AJ, Martin P, Jones PD. Advances and Future Directions in the Treatment of Hepatocellular Carcinoma. Gastroenterol Hepatol (N Y) 2017;13:398-410.
29. Molitoris JK, Diwanji T, Snider JW 3rd, et al. Advances in the use of motion management and image guidance in radiation therapy treatment for lung cancer. J Thorac Dis 2018;10:S2437-50. [Crossref] [PubMed]
30. Rusthoven KE, Kavanagh BD, Cardenes H, et al. Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol 2009;27:1572-8. [Crossref] [PubMed]
31. Kalogeridi MA, Zygogianni A, Kyrgias G, et al. Role of radiotherapy in the management of hepatocellular carcinoma: A systematic review. World J Hepatol 2015;7:101-12. [Crossref] [PubMed]
32. Herfarth KK, Debus J, Lohr F, et al. Stereotactic single-dose radiation therapy of liver tumors: results of a phase I/II trial. J Clin Oncol 2001;19:164-70. [Crossref] [PubMed]
33. Katz AW, Carey-Sampson M, Muhs AG, et al. Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases. Int J Radiat Oncol Biol Phys 2007;67:793-8. [Crossref] [PubMed]
34. Andratschke N, Nieder C, Heppt F, et al. Stererotactic radiation therapy for liver metastases: factorsaffecting local control and survival. Radiat Oncol 2015;10:69. [Crossref] [PubMed]
35. Rubio C, Hernando-Requejo O, Zucca Aparicio D, et al. Image guided SBRT for multiple liver metastases with ExacTrac(®) Adaptive Gating. Rep Pract Oncol Radiother 2017;22:150-7. [Crossref] [PubMed]
36. Sharma SD. Unflattened photon beams from the standard flattening filter free accelerators for radiotherapy: Advantages, limitations and challenges. J Med Phys 2011;36:123-5. [Crossref] [PubMed]
37. Bedford JL. Treatment planning for volumetric modulated arc therapy. Med Phys 2009;36:5128-38. [Crossref] [PubMed]
38. Muñoz-Montplet C, Fuentes-Raspall R, Jurado-Bruggeman D, et al. Dosimetric Impact of Acuros XB Dose-to-Water and Dose-to-Medium Reporting Modes on Lung Stereotactic Body Radiation Therapy and Its Dependency on Structure Composition. Adv Radiat Oncol 2021;6:100722. [Crossref] [PubMed]
39. Hawkins MA, Bedford JL, Warrington AP, et al. Volumetric modulated arc therapy planning for distal oesophageal malignancies. Br J Radiol 2012;85:44-52. [Crossref] [PubMed]
40. Sankaralingam M, Glegg M, Smith S, et al. Quantitative comparison of volumetric modulated arc therapy and intensity modulated radiotherapy plan quality in sino-nasal cancer. J Med Phys 2012;37:8-13. [Crossref] [PubMed]
41. Prendergast BM, Fiveash JB, Popple RA, et al. Flattening filter-free linac improves treatment delivery efficiency in stereotactic body radiation therapy. J Appl Clin Med Phys 2013;14:4126. [Crossref] [PubMed]
42. Chaswal V, Weldon M, Gupta N, et al. Commissioning and comprehensive evaluation of the ArcCHECK cylindrical diode array for VMAT pretreatment delivery QA. J Appl Clin Med Phys 2014;15:4832. [Crossref] [PubMed]
43. Tattenberg S, Hyde D, Milette MP, et al. Assessment of the Sun Nuclear ArcCHECK to detect errors in 6MV FFF VMAT delivery of brain SABR using ROC analysis. J Appl Clin Med Phys 2021;22:35-44. [Crossref] [PubMed]