Abstract
Objective:
This study aims to methodically explore and evaluate the effectiveness of volumetric-modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) with both flattened and unflattened 6MV beams for treating pharyngeal carcinomas.
Materials and Methods:
Twenty patients who had previously undergone treatment for advanced pharyngeal cancer were randomly chosen. They were replanned using a fixed nine-field dynamic IMRT and VMAT with RapidArc using both 6MV flattened and unflattened beams. A total of 80 similar treatment plans were generated for the TrueBeam SVC setup. These plans were assessed for target coverage, maximum and mean doses to the organs at risk, monitor unit (MU), beam-on time, dose to healthy tissue, and other indicators of dose quality.
Results:
Target coverage was nearly identical across all the techniques. VMAT (6FF and 6FFF) achieved equivalent or superior target coverage while plans give better sparing of mean doses of parotid glands, esophagus, larynx, and maximum dose of the spinal cord while maintaining equivalent maximum dose of the brainstem. The MUs required for VMAT plans were about 4–5 times less than that of IMRT plans, additionally, the 6MV plan shows 20%–30% lesser MU than 6FFF plans in both techniques.
Conclusions:
VMAT-6FFF shows fewer hot spots in the planning target volume (PTV) high-risk volume and equivalent or higher hot spots in the PTV intermediate-risk and PTV low-risk volumes. In terms of treatment time, VMAT 6FF has fewer MUs than VMAT 6 FFF. Hence, it shows that VMAT 6FF has less treatment time.
Keywords: 6MV flattened beam, dynamic IMRT, intensity-modulated radiotherapy, pharyngeal cancer, unflattened beam, volumetric-modulated arc therapy
INTRODUCTION
The pharynx is a muscular tube that connects the mouth and nose to the voice box and swallowing tube. It starts at the base of the skull and ends at the lower edge of the cricoid cartilage (C6) level. Pharyngeal cancer, a form of head-and-neck cancer (HNC), originates in the oropharynx tissue. The nasopharynx lies at the top of the pharynx, situated behind the nose. The oropharynx is in the middle, positioned beneath the nasopharynx. The hypopharynx represents the lowest section of the pharynx, connecting to both the windpipe and the swallowing tube. HNC ranks as the seventh most prevalent cancer worldwide, with approximately 888,000 new cases and nearly 50% of deaths each year. In India, the incidence of HNC is increasing annually, projected to reach 2.1 million new cases by 2040 as per GLOBOCON2020 data, making up 30% of all cancer cases, following cervical and breast cancer closely.[1] HNC is a technically challenging treatment site in radiation oncology due to the complex anatomy and numerous organs at risk (OARs) near targets.
External beam radiation therapy is a common treatment for many patients diagnosed with HNC, either used alone or alongside surgery and/or chemotherapy. Radiotherapy can be utilized in various methods to address pharyngeal cancer effectively by precisely targeting the tumor. The introduction of advanced radiotherapy devices, using high-definition multi-leaf collimator (HD-MLC), enables precise treatment administration. Contemporary methods for implementing radiotherapy techniques are intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT).
Intensity-modulated radiation therapy (IMRT) offers improved dose distribution within the target area and reduced radiation exposure to OAR, notably the parotid glands and spinal cord. However, IMRT requires intricate treatment planning, a higher number of treatment beams, and monitor units (MUs), particularly for HNC cases characterized by extensive target areas, numerous OAR, and increased overlap within the different target volumes. VMAT is a developed form of IMRT, where radiation is administered in a continuous arc as the linear accelerator revolves around the patient. This technique involves adjusting the beam using the MLC, altering the dose rate, and varying the speed of the gantry, rather than employing several fixed fields. Given the complexity of the anatomy in the head-and-neck (H and N) region, a VMAT plan usually consists of 2–3 full or partial arcs, depending on whether the treatment targets are bilateral or unilateral. VMAT plans offer comparable or greater target coverage to fixed gantry IMRT plans. Most importantly, VMAT plans have a significantly shorter treatment time compared to fixed gantry IMRT plans. IMRT and VMAT emerged as a mainstream treatment option for HNC. According to Otto,[2] VMAT improves OARs and healthy tissue sparing, maintains or improves the same degree of target coverage, and reduces beam-on time per fraction. This approach has been clinically implemented in the Eclipse treatment planning software (Varian Medical Systems, Palo Alto, CA) under the name RapidArc (RA).
The flattening filter (FF) is made up of high Z materials and is usually conical in shape to flatten the forward peaked bremsstrahlung spectrum of megavoltage photons. The removal of the filter to obtain FF-free (FFF) beams changes the natural peak shape of the beam profile as compared to the conventional FF photon beam.[3] Furthermore, the main source of photon scatter in the treatment head is eliminated with a resulting reduced head-scatter variation with field size. There is currently a growing interest in using FFF linear accelerators for clinical purposes. Chung et al. reported that removing the FF increases the dose rate and reduces the head scatter, neutron contamination, and out-of-field and penumbra areas. They concluded that unflattened beams possess high efficiency compared to flattened beams. However, FFF beams have surface and build-up doses more than flattening beams, yet this difference is not considered critical for ensuring patient safety.[4]
FFF beams are utilized in both IMRT and VMAT treatment planning due to their practical benefits.[5] The utilization of FFF beams for cancer treatment has been progressively on the rise annually. Enhancing the dose rate using FFF beams contributes to a decrease in the total treatment duration.[3,6] The most significant time-saving advantage is achieved when combining arc treatment with FFF beams. Nonetheless, in this study, we will focus on the use of FFF beams in both IMRT and VMAT treatment planning due to their increasing accessibility in the field of radiotherapy.
Recent studies have examined the dosimetric difference between IMRT and VMAT for various cancers, with the consensus being that VMAT produces a similar or superior plan to IMRT with a more efficient delivery.[7,8,9,10] Therefore, this study aims to quantitatively assess the dosimetric differences between unflattened and flattened beams produced by a C-Arm medical accelerator (TrueBeam SVC M/s Varian Medical System, Palo Alto, CA) using intensity-modulated radiation therapy (IMRT) and VMAT. The study also seeks to determine the effectiveness of this specific treatment plan combination among the four plans for treating pharyngeal (nasopharynx, oropharynx, and hypopharynx) cancers.
MATERIALS AND METHODS
Patient characteristics
For this prospective study, 20 previously treated patients aged 32–77 years were identified from the institutional clinical database. The 16 male and 4 female patients selected had been definitively treated for squamous cell carcinoma of the nasopharynx (n = 4), oropharynx (n = 9), and hypopharynx (n = 7).
Linear accelerator and treatment planning system
TrueBeam SVC version 3.0 Linac is equipped with 6 photon energies and 5 electron energies. This tungsten 120-leaf (High Definition-HD) collimator has 32 central pairs of leaf width of 2.5 mm and 28 outer pairs having 5 mm leaf width projected at the isocenter. The total length across leaves of HDMLC is 22 cm at the isocentric plane. To reduce interleaf leakage, leaf sides are designed with a “tongue-and-groove” arrangement, where dovetails shape the complementary tongue or groove regions of adjacent leaves. This structure reduces the interleaf fluence when the leaf sides are exposed to the radiation beam. The machine can generate a maximum MLC speed of 2.5 cm/s with variable dose rates. MV imager panel is equipped with amorphous silicon (a-Si) 1200 scintillation detector panel with an active area of 43 cm × 43 cm and a maximum irradiated area of 30 cm × 40 cm. Beams were calibrated following the American Association of Physicists in Medicine Task Group 51 (TG-51) formalism 100MU corresponds to 1 Gy at the depth of maximum dose for source-to-surface distance 100 cm and field size of 10 cm × 10 cm.
Treatment plans were created using the Eclipse Treatment Planning System (TPS) (Varian Medical Systems) version 17.00.00, utilizing both FFF and FF beams for 6MV energy. The objectives included achieving target doses, minimizing doses to OAR, improving conformity and homogeneity index (HI), and reducing integral doses to normal tissues. Both IMRT and VMAT plans were executed using the Acuros XB (AXB) Version 17.0.1 algorithm (Varian Medical Systems, Palo Alto, CA), which iteratively solves the Linear Boltzmann Transport Equation, demonstrating comparable accuracy to Monte Carlo calculations in a heterogeneous medium. The optimization process involves an iterative inverse planning method that simultaneously optimizes the MLC positions, dose rate, and gantry rotation speed to achieve the desired dose distribution.
Planning objectives
A simulation of a patient was carried out using a GE Revolution Evo-128 slice computed tomography scanner with a slice thickness of 2.5 mm in the supine position and normal breathing with arms placed along the body. A neck support was utilized, and a custom-fitted Aquaplast mask was applied for immobilization. The scanning process covered the area from the vertex to the fourth thoracic vertebrae consistently for all patients.
The scans were sent to the Eclipse treatment planning station for contouring by the treated radiation oncologist and then proceeded with the planning procedure. The target areas and OARs were defined based on the guidelines of the International Commission on Radiation Units and Measurements (ICRU-62). Each patient underwent four treatment plans.
Dose prescription and planning techniques
All patients were planned in three dose levels employing a simultaneously integrated boost (SIB) approach in 35 equal treatment fractions. The primary gross tumor volume and pathologic lymph node metastases were determined by the treated radiation oncologist. Planning target volume high risk (PTV-HR) is the clinically and radiologically demonstrable tumors including the nodal involvement which is prescribed a total dose of 70 Gy at 2 Gy per fraction. In addition, two other elective PTVs were designated as PTV intermediate risk (PTV-IR) and are considered to be areas of high risk of subclinical disease extension, which is prescribed 63 Gy at 1.8 Gy per fraction, and PTV low-risk (PTV-LR) is prescribed 56 Gy at 1.6 Gy per fraction for low-risk and subclinical diseases.
Maximum and mean volumes are 406.7 cc and 192.81 cc for PTV HR, 734.2 cc and 369.39 cc for PTV IR, and 783.4 cc and 200.09 cc for PTV LR, respectively. The planning objective was to achieve a minimum dose (defined as D98%) to PTV >95% prescribed dose and a maximum dose (defined as D2%) <107%. The dose constraints to the OARs were determined using the Radiation Therapy Oncology Group (RTOG). The maximum doses (Dmax) specified for the spinal cord, brain stem (BS), and optic nerve were 46 Gy, and 54 Gy, respectively. The mean dose (Dmean) set for planning risk volume (PRV) cochlea, parotids (left and right analyzed separately), mandible, larynx, and esophagus were <45 Gy, <26 Gy, <40 Gy, <45 Gy, and <40 Gy, respectively.
IMRT and VMAT plans were created using 6MV photon beams with flattened and unflattened beams on a Varian TrueBeam SVC (Varian Medical Systems, Palo Alto, CA) equipped with 120-leaf HD MLC. IMRT plans utilize a dynamic delivery approach, while VMAT plans to employ a double arc technique. In Eclipse TPS, the VMAT is called RA. The optimization constraints and priority levels were consistent for IMRT and VMAT plans. The upper limits for the dose rate for 6FF and 6FFF beams were 600 and 1400 MU/min, respectively. The calculation grid spacing was kept at 2.5 mm.
Optimization was performed with a photon optimizer (PO_17.0.1) with 4 iteration steps involved and volume dose calculation was performed with a GPU-based AXB _ 17.0.1 algorithm. For each patient, four plans were prepared with similar plan objectives (6FF-IMRT, 6FFF-IMRT, 6FF-VMAT, and 6FFF-VMAT). For IMRT, gantry angles were fixed at 0°, 40°, 80°, 120°, 160°, 200°, 240°, 280°, and 320°. Beam angles were selected in such a way as to avoid the opposite entrance. The VMAT consists of two arcs; clockwise (181.0 CW 179.0) and counterclockwise (179.0 CCW 181.0) direction and collimator angles set to 30 and 330 were used, respectively. All beam angles are set in a coplanar direction.
Plan evaluation parameters
Quantitative assessment of plans relied on the standard dose–volume histogram (DVH) analysis, using the DVH estimation algorithm version 17.0.1 for both targets and OARs. Various metrics were defined for each PTV, including D98% (minimum dose received by 98% of the volume), D2% (maximum dose received by 2% of the volume), and D50% (mean dose received by 50% of the volume), concerning to V95% and V107% (volume receiving at least 95% and up to 107% of the prescribed dose). In addition, parameters such as conformity index (CI), HI, remaining volume at risk (RVR), standard deviation (SD), MUs, maximum dose (Dmax), mean dose (Dmean), and 1cc volume for OARs were assessed.
Conformity index
The degree of conformality of the plans was measured with a CI, which quantitatively assesses the quality of the treatment plan. The CI is defined as the ratio between the patient volume receiving 95% of the prescribed isodose volume and the total volume of the PTV.
Conformity Index (RTOG) = VRI/TV
VRI = Reference isodose volume (V95% is taken as reference isodose volume as per ICRU 62).
TV = Target volume
A perfectly conformal plan is described as CI = 1. Therefore, as the CI approaches 1, the plan is more conformal.
Homogeneity index (international commission on radiation units 83)
HI is a measure of dose distribution uniformity across target volume.
The homogeneity of the dose distribution was measured by D2%–D98% for each PTV and expressed as HI = (D2%–D98%)/(D50%).
Where D2%, D50%, and D98% are the doses received by 2%, 50%, and 98% volumes of PTV, respectively.
The homogeneity value ranges from 0 to 1. The lower the HI value, the better dose homogeneity. The ideal value of the HI is 0. A higher value represents a lack of homogeneity.
Gradient index
GI technically represents the measure of dose fall-off. It is used to evaluate radiation dose gradient outside the target, principally a ratio of half of prescription isodose volume to the reference isodose volume.
GI = V (Rx/2)/VRI
V (Rx/2) =50% isodose volume and
VRI = Reference isodose volume (95%).
Since the three target volumes (PTV-HR, PTV-IR, and PTV-LR) overlap in some cases, and in many cases, these volumes are in proximity to each other, the gradient index is calculated specifically for the PTV-HR volume.
Skin surface dose
The skin dose associated with radiotherapy may be of interest for clinical evaluation or investigating the risk of late effects.[11,12] VMAT and IMRT plans were designed without any specific protection of the skin but aimed at creating treatment plans that were clinically acceptable and feasible for delivery. The International Commission on Radiological Protection suggests evaluating the skin dose at a depth of 0.07 mm for the basal layer and 1 mm for the dermal layer. In this research, to determine the maximum dose at the skin surface, a 3-mm skin contour was delineated by creating a shell layer inside the patient’s body contour in all axial slices, including those containing PTVs.
Remaining volume at risk
The RVR, refers to the patient’s outer shape excluding target volumes and OARs, as defined by the ICRU-83 report. The RVR is clinically important in the plan evaluating process. If not carefully considered, there is a risk of overlooking areas within the patient receiving high doses without detection. The RVR is particularly valuable for assessing low-dose radiation exposure to estimate the likelihood of long-term effects, such as carcinogenesis, especially in young patients.[13] The RVR contours are created to analyze the impact of low doses by quantifying the volumes exposed to V20 Gy, V 10 Gy, and V 5 Gy.
Statistical analysis
Descriptive and inferential statistical analysis has been carried out in the present study. Results on continuous measurements are presented on mean ± SD (Min–Max) and results on categorical measurements are presented in number (%). Significance is assessed at a 5% level of significance. The one-way analysis of variance is employed to determine whether there are any statistically significant differences between the means of three or more independent (unrelated) groups. Paired t-test is a test that is based on the differences between the values of a single pair that is one deducted from the other is used in this study. The Statistical software, namely SPSS 22.0 (SPSS, Inc., Chicago, IL, USA) and R environment ver. 3.2.2 were used for the analysis of the data and Microsoft Word and Excel were used to generate graphs, tables, etc., P = 0.01 < P ≤ 0.05 was considered to be moderately significant (*) whereas P ≤ 0.01 was considered strongly significant (**).
RESULTS
The PTV was created by adding a margin around the clinical target volume (CTV) to account for uncertainties in treatment setup and tissue internal movement. Typically, a uniform expansion of 5 mm is added around the CTV to establish each respective PTV. The median age of the participants was 54 years, ranging from 32 to 77 years. Among the list, nine patients (45%) were under 50 years old, four patients (20%) were aged between 51 and 60 years, and seven patients (35%) were over 60 years old. To ensure the effectiveness of the treatment outcome, it is essential to include every single cancer cell by giving an adequate margin to the tumor volumes. Figure 1 shows the three different color washes for three different dose levels for a single patient in four separate plans. Figure 2 illustrates the evaluation of PTV coverage for the four plans by overlapping them in one DVH. Figure 3 gives an overview of the numerical results from DVH analysis on OARs in a single patient. Figure 4 DVH analysis on OARs of a hypopharynx case.
Figure 1.
Different dose levels of planning target volume coverage in a Ca Hypopharynx case. IMRT: Intensity-modulated radiation therapy
Figure 2.
Planning target volume coverage for all four different plans overlapped in a single dose–volume histogram. PTV: Planning target volume, IMRT: Intensity-modulated radiation therapy
Figure 3.
Dose–volume histogram analysis of planning risk volume (PRV) brain stem and PRV SC in a hypopharynx case. PRV: Planning risk volume, IMRT: Intensity-modulated radiation therapy, VMAT: Volumetric-modulated arc therapy
Figure 4.
Dose–volume histogram analysis on organs at risks of a hypopharynx case. RVR: Remaining volume at risk
The IMRT 6FF and 6FFF plan comparison showed no significant difference in PTV coverage and conformity index. However, the 6FFF IMRT plan demonstrated notably improved homogeneity for the PTV HR volume compared to the IMRT 6FF plan as shown in Table 1. In addition, the V105% was slightly higher for the FFF beams than the flattened beams. This is likely due to the increased head scatter dose with the unflattened beams, as evidenced by the significant P value. In other words, the flattened beam plans had smaller volumes of high-dose “hot spots” compared to the unflattened beam plans, removing the filter to obtain FFF beams changes the natural peak of the beam shape. Table 2 reports the numerical analysis of dose coverage between VMAT 6FF and VMAT 6FFF and found that CI, GI, and HI are comparable and their mean values are 0.98 and 0.98, 1.02 and 1.02, and 0.07 and 0.08, respectively. Figure 5 illustrates the HI and CI comparison for all four plans. V105% is higher for VMAT-6FFF (P < 0.001) due to the brag peak of the unflattened beam, while target coverage is higher for PTV IR volume in VMAT 6FF than VMAT-6FFF (P = 0.031). Despite the large volume, both IMRT and VMAT techniques in flattened and unflattened beams could yield CI −0.98 ± 0.04, and HI −0.07 ± 0.03.
Table 1.
Comparison of dose coverage between intensity-modulated radiation therapy 6 flattening filter and intensity-modulated radiation therapy 6 flattening filter-free
| Variables | IMRT 6MV | IMRT 6FFF | Difference | 95% CI of the difference | P | |
|---|---|---|---|---|---|---|
|
| ||||||
| Lower | Upper | |||||
| PTV HR | ||||||
| V95% | 97.2±2.08 | 97.34±1.96 | −0.148 | −0.453 | 0.156 | 0.321 |
| V105% | 2.76±5.33 | 5.4±8.17 | −2.640 | −4.875 | −0.404 | 0.023* |
| HI | 0.08±0.03 | 0.09±0.03 | −0.005 | −0.011 | 0.000 | 0.057 |
| CI | 0.98±0.02 | 0.98±0.01 | −0.004 | −0.014 | 0.005 | 0.360 |
| GI | 1.03±0.01 | 1.04±0.01 | 0.00086 | −0.006 | 0.008 | 0.802 |
| PTV IR | ||||||
| V95% | 97.05±2.18 | 97.62±2.01 | −0.575 | −1.564 | 0.415 | 0.239 |
| V105% | 9.66±9.61 | 12.03±8.35 | −2.370 | −5.287 | 0.547 | 0.105 |
| HI | 0.1±0.03 | 0.1±0.02 | −0.001 | −0.011 | 0.009 | 0.850 |
| CI | 0.98±0.02 | 0.99±0.01 | −0.003 | −0.012 | 0.007 | 0.555 |
| PTV LR | ||||||
| V95% | 98.57±2.77 | 98.13±2.06 | 0.435 | −0.404 | 1.275 | 0.291 |
| V105% | 5.01±7.37 | 9.72±19.23 | −4.705 | −12.756 | 3.345 | 0.236 |
| HI | 0.11±0.03 | 0.11±0.04 | 0.003 | −0.009 | 0.015 | 0.623 |
| CI | 0.98±0.04 | 0.99±0.01 | −0.008 | −0.026 | 0.010 | 0.350 |
HI: Homogeneity index, CI: Conformity index, GI: Gradient index, PTV HR: Planning target volume high risk, PTV LR: Planning target volume low-risk, PTV IR: Planning target volume intermediate risk, IMRT: Intensity-modulated radiation therapy, 6FFF: 6 flattening filter-free, CI: Conformity index, 6MV: Flattening filter beam, *Significance
Table 2.
Comparison of dose coverage variables between volumetric-modulated arc therapy 6 flattening filter and volumetric-modulated arc therapy 6 flattening filter-free
| Variables | VMAT 6MV | VMAT 6FFF | Difference | 95% CI of the difference | P | |
|---|---|---|---|---|---|---|
|
| ||||||
| Lower | Upper | |||||
| PTV HR | ||||||
| V95% | 97.68±1.78 | 97.73±1.74 | −0.044 | −0.270 | 0.181 | 0.684 |
| V105% | 0.67±0.62 | 3.27±3.35 | −2.595 | −3.913 | −1.276 | <0.001** |
| HI | 0.07±0.03 | 0.08±0.03 | −0.006 | −0.017 | 0.005 | 0.253 |
| CI | 0.98±0.01 | 0.98±0.01 | 0.000 | −0.004 | 0.004 | 0.934 |
| GI | 1.02±1.06 | 1.02±1.06 | 0.00183 | −0.004 | 0.001 | 0.134 |
| PTV IR | ||||||
| V95% | 97.6±2 | 95.66±4.97 | 1.931 | 0.194 | 3.668 | 0.031* |
| V105% | 16.45±30.55 | 11.64±5.8 | 4.814 | −9.813 | 19.441 | 0.499 |
| HI | 0.1±0.02 | 0.1±0.02 | −0.005 | −0.011 | 0.002 | 0.135 |
| CI | 0.98±0.04 | 0.98±0.02 | −0.007 | −0.018 | 0.005 | 0.251 |
| PTV LR | ||||||
| V95% | 98.03±1.99 | 98.32±2.36 | −0.288 | −0.943 | 0.367 | 0.368 |
| V105% | 15.6±32.26 | 20.32±38.37 | −4.719 | −16.786 | 7.347 | 0.423 |
| HI | 0.12±0.04 | 0.13±0.03 | −0.006 | −0.016 | 0.003 | 0.180 |
| CI | 0.97±0.04 | 0.98±0.04 | −0.009 | −0.020 | 0.001 | 0.074 |
*Significance. **Strongly significance. HI: Homogeneity index, CI: Conformity index, GI: Gradient index, PTV HR: Planning target volume high risk, PTV LR: Planning target volume low-risk, PTV IR: Planning target volume intermediate risk, VMAT: Volumetric-modulated arc therapy, 6FFF: 6 flattening filter-free, CI: Conformity index, 6MV: Flattening filter beam
Figure 5.
Homogeneity index and conformity index comparison for different treatment plans. CI: Conformity index, HI: Homogeneity index, IMRT: Intensity-modulated radiation therapy
Excellent coverage was achieved for all three PTVs with an average of over 95% of the prescription dose delivered to each PTV (high risk, intermediate risk, and low risk). Concerning the delivery of 105% of the prescribed dose, the VMAT plan demonstrated a smaller volume of the target area receiving this dose (0.67 ± 0.62) compared to the IMRT plan (2.76 ± 5.33). Furthermore, when comparing the use of 6FF and 6FFF beams in VMAT, the 6FF beams exhibited a significantly lower volume of the target area (0.67 ± 0.62) receiving the 105% dose than the 6FFF beams (3.27 ± 3.35) with a statistical significance of P < 0.001**. Table 2 shows a comparison of dose coverage variables between VMAT 6FF and VMAT 6FFF. Table 3, a comparison of dose coverage variables between IMRT 6FF and VMAT 6FF, and Table 4 shows a comparison of dose coverage variables between IMRT 6FFF and VMAT 6FFF. Table 5 provides a summary of the dosimetric comparison of OARs, including their average deviation and the outcomes of statistical analysis for various plan combinations. Table 6 illustrates the comparison of the RVR of V20/V10/V5 between IMRT (6FF and 6FFF) whereas Table 7 demonstrates the same for VMAT (6FF and 6FFF).
Table 3.
Comparison of dose coverage variables between intensity-modulated radiation therapy 6 flattening filter and volumetric-modulated arc therapy 6 flattening filter
| Variables | IMRT 6MV | VMAT 6MV | Difference | 95% CI of the difference | P | |
|---|---|---|---|---|---|---|
|
| ||||||
| Lower | Upper | |||||
| PTV HR | ||||||
| V95% | 97.2±2.08 | 97.68±1.78 | −0.485 | −1.231 | 0.261 | 0.189 |
| V105% | 2.76±5.33 | 0.67±0.62 | 2.087 | −0.195 | 4.368 | 0.071 |
| HI | 0.08±0.03 | 0.07±0.03 | 0.011 | −0.005 | 0.026 | 0.164 |
| CI | 0.98±0.02 | 0.98±0.01 | −0.005 | −0.014 | 0.005 | 0.291 |
| GI | 1.02±1.07 | 1.02±1.06 | 0.00314 | −0.008 | 0.002 | 0.221 |
| PTV IR | ||||||
| V95% | 97.05±2.18 | 97.6±2 | −0.548 | −1.507 | 0.411 | 0.247 |
| V105% | 9.66±9.61 | 16.45±30.55 | −6.794 | −22.374 | 8.786 | 0.373 |
| HI | 0.1±0.03 | 0.1±0.02 | 0.001 | −0.008 | 0.011 | 0.745 |
| CI | 0.98±0.02 | 0.98±0.04 | 0.007 | −0.005 | 0.019 | 0.250 |
| PTV LR | ||||||
| V95% | 98.57±2.77 | 98.03±1.99 | 0.533 | −0.157 | 1.224 | 0.123 |
| V105% | 5.01±7.37 | 15.6±32.26 | −10.584 | −25.632 | 4.464 | 0.157 |
| HI | 0.11±0.03 | 0.12±0.04 | −0.011 | −0.023 | 0.000 | 0.045* |
| CI | 0.98±0.04 | 0.97±0.04 | 0.008 | −0.003 | 0.020 | 0.151 |
HI: Homogeneity index, CI: Conformity index, GI: Gradient index, PTV HR: Planning target volume high risk, PTV LR: Planning target volume low-risk, PTV IR: Planning target volume intermediate risk, VMAT: Volumetric-modulated arc therapy, IMRT: Intensity-modulated radiation therapy, CI: Conformity index, 6MV: Flattening filter beam, *Significance
Table 4.
Comparison of dose coverage variables between intensity-modulated radiation therapy 6 flattening filter-free and volumetric-modulated arc therapy 6 flattening filter-free
| Variables | IMRT 6FFF | VMAT 6FFF | Difference | 95% CI of the difference | P | |
|---|---|---|---|---|---|---|
|
| ||||||
| Lower | Upper | |||||
| PTV HR | ||||||
| V95% | 97.34±1.96 | 97.73±1.74 | −0.381 | −1.075 | 0.313 | 0.265 |
| V105% | 5.4±8.17 | 3.27±3.35 | 2.132 | −0.685 | 4.948 | 0.130 |
| HI | 0.09±0.03 | 0.08±0.03 | 0.010 | 0.002 | 0.018 | 0.022* |
| CI | 0.98±0.01 | 0.98±0.01 | −0.001 | −0.006 | 0.004 | 0.769 |
| GI | 1.02±1.06 | 1.02±1.06 | 0.00584 | −0.010 | −0.002 | 0.007** |
| PTV IR | ||||||
| V95% | 97.62±2.01 | 95.66±4.97 | 1.958 | −0.182 | 4.097 | 0.071+ |
| V105% | 12.03±8.35 | 11.64±5.8 | 0.390 | −4.402 | 5.182 | 0.867 |
| HI | 0.1±0.02 | 0.1±0.02 | −0.003 | −0.012 | 0.006 | 0.507 |
| CI | 0.99±0.01 | 0.98±0.02 | 0.003 | −0.005 | 0.012 | 0.428 |
| PTV LR | ||||||
| V95% | 98.13±2.06 | 98.32±2.36 | −0.191 | −1.019 | 0.638 | 0.636 |
| V105% | 9.72±19.23 | 20.32±38.37 | −10.598 | −32.022 | 10.826 | 0.313 |
| HI | 0.11±0.04 | 0.13±0.03 | −0.021 | −0.036 | −0.005 | 0.012* |
| CI | 0.99±0.01 | 0.98±0.04 | 0.007 | −0.011 | 0.026 | 0.423 |
*Significance. **Strongly significance. HI: Homogeneity index, CI: Conformity index, GI: Gradient index, PTV HR: Planning target volume high risk, PTV LR: Planning target volume low-risk, PTV IR: Planning target volume intermediate risk, VMAT: Volumetric-modulated arc therapy, IMRT: Intensity-modulated radiation therapy, 6FFF: 6 flattening filter-free, CI: Conformity index
Table 5.
Summary of dosimetric comparison of organs at risks
| Statistical comparison of critical organs (mean±SD) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||
| Structures | Variables (Gy) | IMRT 6MV (A) |
IMRT 6FFF (B) |
VMAT 6MV (C) |
VMAT 6FFF (D) |
A vs. B | C vs. D | A vs. C | B vs. D |
| PRV SC | Dmax | 55.61±4.97 | 56.09±4.58 | 53±4.97 | 54.89±4 | 0.136 | 0.124 | 0.013* | 0.14 |
| D1cc | 47.69±3.91 | 48.33±3.67 | 46.93±5.75 | 49.95±4.16 | 0.019* | 0.063+ | 0.534 | 0.030* | |
| SC | Dmax | 46.3±4.79 | 46.5±4.46 | 48.31±3.19 | 49.27±4.48 | 0.54 | 0.116 | 0.009* | <0.001** |
| D1cc | 40.89±3.89 | 41.15±3.64 | 44.67±3.77 | 46.84±4.43 | 0.245 | 0.008** | <0.009* | <0.001** | |
| PRV BS | Dmax | 48.15±8.69 | 48.62±8.82 | 49.13±7.63 | 49.72±8.24 | 0.123 | 0.307 | 0.179 | 0.156 |
| D1cc | 38.38±10.35 | 39.14±10.47 | 40.67±9.3 | 41.11±10.18 | <0.001** | 0.47 | 0.020* | 0.032* | |
| BS | Dmax | 42.06±6.58 | 42.94±6.81 | 44.67±5.62 | 63.8±81.46 | <0.013* | 0.314 | 0.006** | 0.271 |
| D1cc | 32.48±9.64 | 33.28±10.05 | 34.42±8.97 | 36.3±10.25 | <0.017* | 0.298 | 0.247 | 0.018** | |
| R parotid | Dmean | 29.37±5.22 | 29.09±5.09 | 33.06±7.82 | 32.42±7.95 | 0.060+ | 0.035* | <0.001** | <0.001** |
| R parotid-PTV | Dmean | 19.63±4.17 | 19.49±4.55 | 26.56±6.06 | 26.06±5.56 | 0.555 | 0.206 | <0.001** | <0.001** |
| L parotid | Dmean | 29.37±4.19 | 29.1±4.02 | 32.17±5.85 | 32.06±6.44 | 0.0173 | 0.671 | <0.001** | <0.001** |
| L parotid-PTV | Dmean | 18.98±3.35 | 19.51±4.93 | 26.16±5.2 | 25.02±5.19 | 0.511 | 0.588 | <0.001** | 0.006** |
| Mandible | Dmean | 42.81±6.55 | 43.45±7.16 | 46.12±8 | 62.23±95.02 | 0.049* | 0.33 | <0.001** | 0.323 |
| Mandible-PTV | Dmean | 33.77±5.87 | 34.58±6.41 | 39.01±6.68 | 39.15±7.15 | 0.136 | 0.663 | <0.001** | <0.001** |
| RON | Dmax | 6.86±12.93 | 6.03±12.28 | 7.25±12.99 | 6.57±11.25 | 0.004** | 0.077+ | 0.007* | 0.325 |
| LON | Dmax | 6.76±13.09 | 5.95±12.4 | 6.63±11.61 | 6.25±9.87 | 0.023* | 0.166 | 0.8 | 0.452 |
| Skin | Dmax | 76.22±1.73 | 76.35±2.17 | 75.81±1.29 | 76.2±1.6 | 0.403 | 0.034* | 0.301 | 0.521 |
| Esophagus | Dmean | 40.86±6.41 | 41.36±6.28 | 46.33±13.75 | 43.36±5.48 | 0.020* | 0.361 | 0.108 | 0.079 |
| Larynx | Dmean | 42.27±1.72 | 42.22±1.41 | 46.84±5.9 | 46.31±5 | 0.617 | 0.472 | 0.013* | 0.034* |
| PRV Coch RT | Dmax | 25.54±24.29 | 25.48±24.56 | 23.48±24.32 | 25.49±24.29 | 0.658 | 0.392 | 0.49 | 0.983 |
| Dmean | 16.43±18.54 | 16.43±18.53 | 16.93±20.07 | 17.49±19.96 | 1 | 0.531 | 0.695 | 0.314 | |
| PRV Coch LT | Dmax | 28.57±22.34 | 27.81±23.06 | 24.05±22.36 | 26.6±22.23 | 0.431 | 0.267 | 0.179 | 0.333 |
| Dmean | 17.68±16.77 | 16.33±17.08 | 17.56±19.25 | 18.08±19.23 | 0.158 | 0.481 | 0.939 | <0.001** | |
SC: Spinal cord, BS: Brain stem, PRV: Planning risk volume, PRV Coch RT: PRV right cochlea, PRV Coch LT: PRV left cochlea, VMAT: Volumetric-modulated arc therapy, IMRT: Intensity-modulated radiation therapy, 6FFF: 6 flattening filter-free, SD: Standard deviation, RON: Right optic nerve, LOM: Left optic nerve, *Significance, **Strong significance, +No significance
Table 6.
Comparison of remaining volume at risk V20 Gy/V10 Gy/V5 Gy between 6 flattening filter and 6 flattening filter-free in intensity-modulated radiation therapy
| Variables (Gy) | Mean±SD (cc) | Difference | 95% CI of the difference | P | |
|---|---|---|---|---|---|
|
| |||||
| Lower | Upper | ||||
| RVR V20 | |||||
| IMRT-6MV | 1978.65±625.26 | 90.642 | −263.666 | 444.951 | 0.608 |
| IMRT-6FFF | 1888.01±470.83 | ||||
| RVR V10 | |||||
| IMRT-6MV | 2656.61±611.03 | 13.463 | −377.876 | 404.802 | 0.945 |
| IMRT-6FFF | 2643.15±611.58 | ||||
| RVR V5 | |||||
| IMRT-6MV | 3271.06±730.27 | 49.324 | −414.838 | 513.487 | 0.831 |
| IMRT-6FFF | 3221.73±719.81 | ||||
RVR: Remaining volume at risk, SD: Standard deviation, CI: Conformity index, VMAT: Volumetric-modulated arc therapy, IMRT: Intensity-modulated radiation therapy, 6FFF: 6 flattening filter-free, 6MV: Flattening filter beam
Table 7.
Comparison of remaining volume at risk V20 Gy/V10 Gy/V5 Gy between 6 flattening filter and 6 flattening filter-free in volumetric-modulated arc therapy
| Variables (Gy) | Mean±SD (cc) | Difference (cc) | 95% CI of the difference | P | |
|---|---|---|---|---|---|
|
| |||||
| Lower | Upper | ||||
| RVR V20 | |||||
| VMAT-6MV | 2479.76±2933.1 | 633.53 | −710.359 | 1977.428 | 0.346 |
| VMAT-6FFF | 1846.22±459.21 | ||||
| RVR V10 | |||||
| VMAT-6MV | 2649.43±615.1 | −12.774 | −397.990 | 372.442 | 0.947 |
| VMAT-6FFF | 2662.21±588.08 | ||||
| RVR V5 | |||||
| VMAT-6MV | 3472.14±756.74 | 74.051 | −390.600 | 538.703 | 0.749 |
| VMAT-6FFF | 3398.09±693.53 | ||||
RVR: Remaining volume at risk, SD: Standard deviation, CI: Conformity index, VMAT: Volumetric-modulated arc therapy, 6FFF: 6 flattening filter-free, 6MV: Flattening filter beam
Spinal cord
Two treatment plans, IMRT-6FF and 6FFF, met the planning objective of limiting the maximum spinal cord dose to 46 Gy. Conversely, the other two plans, VMAT-6FF and 6FFF, delivered doses of approximately 48.31 ± 3.19 Gy and 49.27 ± 4.48 Gy, respectively. For the 1cc volume, IMRT-6FF exhibited the lowest value of 40.89 ± 3.89, while VMAT-6FFF showed 46.84 ± 4.43. Regarding the PRV of the spinal Cord, VMAT-6FF reached a maximum dose (Dmax) of 53 ± 4.97, whereas IMRT-6FFF had a Dmax of around 56.09 ± 4.58.
Brainstem
The average maximum dose (Dmax) for the BS is 42.06 Gy, 42.94 Gy, 44.67 Gy, and 63.8 Gy for IMRT-6FF, 6FFF, VMAT-6FF, and 6FFF, respectively. This means that VMAT 6FFF resulted in a higher dose to the BS than the other plans. It indicates that using VMAT with an unflattened beam leads to higher maximum doses for critical organs located close to the target regions. IMRT (6FF) plan had an average dose reduction of 2 Gy to this structure than VMAT (6FF) with the P = 0.006 (most significant). Interestingly, the maximum dose (Dmax) for the PRV BS is 49.72 Gy, whereas the dose for the actual BS reaches around 63.8 Gy. This difference occurred because the optimization process only considered dose constraints for the PRV of the BS. Therefore, this research demonstrates the importance of incorporating constraints for both the PRV of the BS and the actual BS during the optimization process.
Parotid glands
The planning goal of keeping the average dose to the parotid-PTV organ below 26 Gy was successfully reached in all four plans. When looking at the actual parotid glands, it was observed that IMRT (6FF and FFF) slightly enhanced the reduction in average dose to both parotids, which was statistically significant (P < 0.001*).
Esophagus
Esophagus doses in VMAT plans were slightly higher than those in IMRT plans but still acceptable, averaging 40.86 Gy and 41.86 Gy for IMRT 6FF and 6FFF, respectively. In comparison, the VMAT doses (6FF and 6FFF) were 46.33 Gy and 43.36 Gy, which is statistically significant (P = 0.020) between flattened and unflattened beams rather than between VMAT and IMRT techniques.
Larynx
In VMAT plans, the doses to the larynx were greater compared to IMRT plans by 4 Gy. Consequently, only IMRT plans achieved the clinical goal of maintaining a mean dose of <45 Gy to the larynx. This variance demonstrates statistical significance (P = 0.013*).
Cochlea
The planning objective of a mean dose of <45 Gy was met by both techniques and energies. VMAT 6FF had an average dose reduction of 8.05% and 15.8% to the right and left cochlea, respectively, than IMRT 6FF in this structure.
Mandible
All plans achieved the objective mandible excluding PTV less than the mean dose of 40 Gy and IMRT 6FF was found to be more effective in sparing the mandible. The mandible is not prioritized because of its late toxic effect.
Skin
The measured Dmax for 6FF and 6FFF beams are 1.5 cm and 1.38 cm, respectively. The skin dose depends on the magnitude of the energy of the photon.[12] FFF beams have higher skin dose as compared to the FF beam plans (P = 0.034*). It is advantageous to use the VMAT 6FFF beam combinations for patients needing higher surface doses.
Remaining volume at risk
The planning objectives for healthy tissue were not formalized in numerical terms but the objective was to limit its exposure as much as possible. In this respect, the volume of 20 Gy, 10 Gy, and 5 Gy received the area of 1978 cc, 2656cc, and 3271cc, respectively, for IMRT 6FF and with a negligible difference for the IMRT 6FFF plan (Avg. P =0.794). In VMAT plans, 6FFF beams show slightly lesser volumes of 20 Gy, 10 Gy, and 5 Gy compared to 6FF beams. Tables 6 and 7 show the comparison of the average volume of RVR. Figure 6 shows the comparison of different RVR doses. In conclusion, VMAT6FFF beams irradiated the lesser remaining volume when compared to all other plans. This is because the FFF beams could reduce collimator scatter and head leakage and consequently reduce the out-of-field dose.[9]
Figure 6.
Comparison of different remaining volume at risk doses. IMRT: Intensity-modulated radiation therapy, VMAT: Volumetric-modulated arc therapy, RVR: Remaining volume at risk
Monitor units
All IMRT and VMAT plans were executed on a Varian TrueBeam SVC Linear Accelerator in Quality Assurance mode to ensure the accuracy of the beam and confirm the MUs. The number of MUs for the IMRT flattened and unflattened plans were 2106 ± 429.47 and 2884 ± 495.94, respectively. For the VMAT plans, the MUs were 584.9 ± 89.42 and 661.1 ± 93.4, respectively. Overall VMAT plans have 4–5 times fewer MUs than IMRT plans [Table 8 and Figure 7]. In addition, IMRT (6FF) plans can deliver the prescribed dose of 2 Gy/fr in the SIB method with 27% fewer MUs compared with IMRT (6FFF) similarly VMAT (6FF) can deliver the same dose with 13% fewer MUs than VMAT (6FFF). In summary, a flattened 6FF beam can deliver fewer MUs than an unflattened 6 (FFF) beam in both VMAT and IMRT techniques.
Table 8.
Comparison of average monitor units of each plan
| IMRT-6FF | IMRT-6FFF | P | Significance | |
|---|---|---|---|---|
| MUs | 2106±429.47 | 2884±495.94 | <0.001** | Strong |
|
| ||||
| VMAT-6FF | VMAT-6FFF | P | Significance | |
|
| ||||
| MUs | 584.9±89.42 | 661.1±93.4 | <0.001** | Strong |
MUs: Monitor units, IMRT: Intensity-modulated radiation therapy, 6FFF: 6 flattening filter-free, VMAT: Volumetric-modulated arc therapy
Figure 7.
Comparison of monitor units for different plans. MU: Monitor unit, IMRT: Intensity-modulated radiation therapy, VMAT: Volumetric-modulated arc therapy
DISCUSSIONS
External beam radiotherapy aims to control tumors while sparing the adjacent normal structures. In other words, it increases the therapeutic index by lowering the normal tissue complications. Simplicity increases the tumor control probability (TCP) and minimizes the normal tissue complication probability (NTCP). Considering the development of modern computational and sophisticated TPSs in radiotherapy, homogeneous dose distributions are not required. Hence, the use of FFF beams increased substantially in all Linac machines. Consequently, the additional advantage is that the exposure time may be shorter and, therefore, the probability of patient movements between fractions may be reduced.
This study compares the VMAT (RA) and dynamic IMRT methods using both flattened and unflattened beams for treating pharyngeal (H and N) cancers. While previous studies have explored similar topics, few have specifically examined the importance of flattened versus unflattened beams. Different studies have been conducted on different energies 6, 10, 15, and 18 MV to assess the dosimetric characteristics of FFF authors reported that removing the filter increases the dose rate and reduces the head scatter, neutrons contamination, out-of-field, and penumbra doses.[14] They concluded that unflattened beams possess high efficiency compared to flattened beams. However, FFF beams have surface and build-up doses more than that of flattening beams, but their impact is not significant for patient safety.
Different planning studies have compared the VMAT with conventional step-and-shoot IMRT in HNCs.[15,16,17,18] Previous researchers concluded the advantage of using an FFF beam for different sites. Xu et al. showed that for frontal lobe glioma, the Dmax and Dmean of PTV in VMAT were increased compared with dIMRT, but no significant result was found in OAR and normal structures. FFF beam plans consumed higher MUs.[19]
Fung-Kee-Fung et al. conducted a prospective study where VMAT plans were preferred over IMRT 90% of the time.[20] VMAT plans, in comparison to IMRT, utilized only a third of the MUs, had shorter treatment durations, and achieved comparable sparing of OAR. While VMAT offered similar dose uniformity, it exhibited lower conformity in delivering the prescribed dose to the PTV than IMRT. In a current study that compared 6FF IMRT with 6FF VMAT, VMAT demonstrated equivalent dose distribution to IMRT. Concerning high-dose areas, VMAT covered a smaller volume at 105%, which was statistically suggestive with a P = 0.071. IMRT outperformed VMAT in terms of the HI for the PTV low-risk volume (P = 0.045*), potentially attributed to tumor extension toward the neck region. Consequently, for larger volumes, IMRT achieved a more uniform dose distribution, whereas VMAT offered comparable coverage with slightly lower homogeneity.
Vanetti et al. examined the advantages of volumetric-modulated arc therapy (VMAT) over fixed field intensity-modulated radiation therapy (IMRT) for orohypopharynx and larynx carcinomas.[9] The study found that using double-arc VMAT resulted in enhanced target coverage and homogeneity compared to single-arc VMAT and sliding window IMRT. The research indicated that employing multiple arcs not only improved organ protection but also enhanced target coverage. Following this data, the current study standardized the double arc technique; however, the question remains whether increasing the number of arcs is beneficial for various cancers such as H and N and pelvic cases. Compared to Vanetti et al. conclusion, this research shows the coverage for PTV HR with an average of D95 of 97.5% prescribed dose. Likewise, the coverage for intermediate- and low-risk PTVs appears comparable to that of high-risk volume. When examining various cases involving the hypopharynx, oropharynx, and nasopharynx, it was observed that the coverage varied depending on the case when using IMRT. In contrast, VMAT plans demonstrated enhanced coverage across all types of these cases.
RapidArc allows the generation of adequate dose distribution with high target homogeneity, sufficient sparing of OAR, and minimization of the patient moment compared to IMRT in ovarian cancer the conformity index (P = 0.253) and HI (P = 0.253) were found to be equal between VMAT 6FF and VMAT 6FFF. On the other hand, V105% (P < 0.001**) was notably lower with VMAT 6FF compared to VMAT 6FFF.
Braam et al. showed that the NTCP at several time points after radiation therapy was <20% only if the mean dose to the parotid glands was lower than 25 Gy.[21] In this current study, it was observed that the average mean dose of both left parotid and right parotid received using IMRT was lower compared to VMAT (P < 0.001*).[9,20,21,22,23] However, the difference was not significant when using 6FF and 6FFF beams in both techniques. Specifically focusing on the parotids excluding the PTV, IMRT plans received significantly lower doses than VMAT plans, showing strong statistical significance (P = 0.006**).
The dose to the healthy organ apart from the PTV mainly comes from the collimator transmission and scatter radiation from the LINAC head. In terms of healthy tissue, V20 Gy doses are 500cc lower when using IMRT 6FF instead of VMAT 6MV, and IMRT 6FFF results in a further 100cc decrease (P = 0.608). There is not a significant difference in V10 Gy for all four plans. IMRT 6FFF delivers a 100cc lower dose than VMAT 6FFF for V5 Gy.[9] Although PRV spinal cord and BS doses are elevated above the acceptable limit, this could reduce and bring within the tolerance limit by re-optimization. Both VMAT (RA) and IMRT could result in further reducing exposure to OARs using stricter goals, although this aspect was not the focus of the current study.
Nguyen et al. demonstrated that VMAT showed good treatment options because of the reduction in MUs, shorter treatment delivery time, and reduced overall dose to the OARs while maintaining optimal dose distributions.[24] In this study, it is evident VMAT (6FF) superior treatment option for target coverage and lesser treatment delivery time whereas IMRT 6FF is a more suitable treatment option for reirradiation patients due to its ability to minimize the OARs compared to VMAT 6FF, especially for spinal cord (P < 0.009*) and brainstem (P = 0.006**) doses.
This study’s restriction applies specifically to the Varian TrueBeam SVC HD MLC configuration with the AXB algorithm. The comparison of 6FF and 6FFF beams for IMRT and VMAT for pharyngeal carcinomas can differ when using different MLCs and algorithms. Hence, future research should explore various studies with various plan parameter combinations to help planners select the best combination more easily.
Treatment is delivered rapidly, with a double arc delivery requiring <70 s with VMAT (6FF) and <40 s with VMAT (6FFF). In comparison, typical IMRT (6FF) dynamic delivery for nine fields requires 5 min whereas IMRT (6FFF) requires <3 min. Speed of delivery is a major advantage of VMAT (6-FFF) as it reduces the risk of intrafraction movements. Moreover, the shorter treatment time is more convenient for patients and allows for treating more patients in a day.
CONCLUSIONS
This planning and dosimetric study demonstrates that VMAT (RapidArc) is a highly effective technique to treat pharyngeal cancer, especially for SIB dose delivery. The VMAT (6FF) delivered the dose rapidly with a strong gradient and a higher conformity index. In contrast, IMRT (6FF) provides a lesser near maximum dose and provides the least OAR dose compared to all other plan combinations hence IMRT (6FF) treatment option is ideal for reirradiation patients. Therefore, VMAT (6FF and 6FFF) proves superior in terms of target coverage effectively, particularly for a simultaneous integrated boost in larger volumes of pharyngeal carcinomas, and is particularly advantageous for adaptive therapy because of its significantly shorter delivery time compared to other combinations. On the other hand, for minimizing the dose to OAR and reducing the near-maximum dose, a suitable combination is IMRT 6FF.
Conflicts of interest
There are no conflicts of interest.
Acknowledgement
The authors would like to acknowledge support from the ICTP through the Associates Programme (2023 - 2028).
Funding Statement
Nil.
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