Summary

METHODS
The dose distributions and in vivo dosimetry results of patients with endometrial (n=10) and cervical (n=10) cancer who underwent external pelvic RT in our department were analyzed retrospectively. The RT planning and 3D in vivo dosimetry data were obtained from the treatment planning system and the iViewDose® (Elekta, Crawley, UK) in vivo quality assurance system. In addition, patient-specific phantom measurements were carried out for each patient with the Alderson Rando phantom. The results were evaluated with 3D gamma analysis method using iViewDose® software. We obtained γ_mean, γ_1%, and γ_γ1% values for each patient with the analysis. Acceptance criteria for these parameters were taken as 0.7, 2.0, and 90%, respectively.

RESULTS
The phantom measurements showed that all treatment plans were applicable. All patients met the passing criteria for ?mean, ?_1%, and ?_?1%. The mean gamma passing rate was 95.1%±1.7 and 96.3%±2.9 for patients with endometrial and cervical cancer, respectively.

CONCLUSION
The EPID-based in vivo dosimetry seems to be usable in clinical routine in the treatment of gynecological cancers. However, field size is the most important limitation of in vivo EPID dosimetry in cases requiring extended field RT.

Introduction

Patient-specific QA in IMRT is often performed before treatment. In particular, errors due to variability in the patient's anatomy, tumor morphology, and the position of the organs at risk (OARs) relative to the target volume cannot be detected by pre-treatment QA.[3] Therefore, the quality of actual treatment remains unclear. In vivo dosimetry is a solution for ensuring the accuracy of the RT delivery. This accuracy can be tested with optically stimulated luminescence dosimetry (OSL), thermoluminescence dosimetry (TLD), film dosimetry, and electronic portal imaging device (EPID).[4-6] While OSL and TLD measure the point dose, film dosimetry has the capability to measure the 2D dose distribution. The EPID on the other hand is a digital MV imaging detector originally designed for the verification of patient positioning during treatment. Due to its dosimetric properties, it can also be utilized in patient-specific QA measurements. Recently, EPIDbased systems are used as in vivo dosimetry systems, since they include the transit dose information.[7-9] In recent years, EPID-based 3D in vivo dosimetry is increasingly used in routine practice. However, data on gynecological patients are still very limited. Since the OARs as the bowel, urinary bladder, and rectum can move and change in shape and dimensions during treatment, the proximity of these OARs to the target volume increases the importance of in vivo dosimetry for gynecological cancers. The variations during treatment can affect the doses to the target and OARs which can result in increased toxicity and decreased local control rates.

In this study, 3D in vivo EPID-based in vivo dosimetry results were examined in patients with endometrial and cervical cancer previously treated in our clinic and a phantom study was additionally performed. The performance and reliability of EPID-based system were evaluated in 3D in vivo QA of gynecological patients.

Methods

In Vivo Measurements
Daily kV cone-beam CT (CBCT) was acquired for each patient. After the positional accuracy was approved, the treatment was started. During treatment, the EPID was in the open position and the transit radiation was collected using the iViewGT® (Elekta, Crawley, UK) software. We used an EPID with amorphous silicon flat panel-type imager (Elekta iViewGT®). The sensitive area of the panel contains 1.024×1.024 pixels which can image up to a 26×26 cm² field size at the isocenter. The collected data were automatically transferred to the iViewDose® (Elekta, Crawley, UK) in vivo QA system. The iViewDose® software can reconstruct the transit dose to the CT images of the patient. In a previous paper, the mathematical aspects of the dose reconstruction algorithm were explained.[10] The iViewDose® also allows performing 3D gamma analysis between the TPS and measured dose. The gamma index (γ) is one of the most commonly used metrics for analyzing the fidelity of IMRT and VMAT plans. It quantifies the difference between measured and calculated dose distributions on a point-by-point basis in terms of both distance to agreement (DTA) and dose differences. The mathematical structure of gamma analysis was previously introduced by Low et al.,[11] in which γ was defined as in Eq.(1).

γ(r_m)=min{⌈(rm,rc)}∀{rc}, (1)

Where the pass-fail criteria are

γ(r_m)≤1, calculation passes,

γ(r_m)>1, calculation fails. (2)

In this study, we used 3D gamma evaluation per fraction for analysis. The mean value of the gamma distribution (γ_mean), the 1% of points have an equal or higher gamma value (γ_1%) and the criteria of 3% dose difference/3mm DTA (γ_≤1%) were examined to evaluate the treatment quality. The pass rate criterion was described as 0.7, 2.0, and 90%, respectively.

The dose reference point (DRP) values were used for the comparison of point dose measurement results. The software allows us to select a structure to define the DRP which is placed in the mass center of the delineated structure. For the selected structures, the algorithm of the iViewDose® software calculates the percentage dose difference between the TPS and EPID doses reconstructed on the treatment CT. The acceptance criterion was set at within 3% dose difference for the planning target volume.

Phantom Measurements
Patient-specific phantom measurements were carried out with the Alderson Rando phantom. The phantom measurement was performed to confirm that the treatment plans were deliverable. For this purpose, the plans were exported to the Alderson Rando phantom"s CT. VMAT plans were re-calculated and irradiated on that phantom to perform gamma analysis verification with the passing criterion of 3% (global)/3 mm. Following, the measurement was compared with the TPS using the iViewDose® software.

Results

Table 1: Dosimetric differences for phantom data (90% passing rate was considered clinically acceptable)

In Vivo Measurements
The results for in vivo measurements are given in Table 2. All patients met the passing criteria for γ_mean, γ_1%, γ_γ1%, and DRP. The mean gamma passing rate was 95.1%±1.7 and 96.3%±2.9 for patients with the endometrial and cervical cancer, respectively. While the mean dose difference at the isocenter in percentage was 1.42±0.94 for patients with endometrial cancer, it was observed 1.59±0.78 for patients with cervical cancer. The maximum dose difference for the DRP was 2.58% for endometrial and 2.55% for cervical cancer, respectively.

Table 2: Dosimetric differences for patient data

Figure 1 displays an example of the TPS dose, EPID dose, gamma analysis results, and dose distributions along the central axis. The blue color in gamma analysis indicates that the difference between the calculated (TPS dose) and measured dose (EPID) is very small. On the contrary, the red color indicates that the region where the difference between the calculated and measured dose exceeds the acceptance criteria. The dose distribution along the central axis also shows that the difference between the calculated and measured dose is very small in and out of the field.

Fig 1: Calculated dose, measured dose, gamma evaluation, and line dose comparison of calculated and measured dose on the central axis for an endometrial and a cervical cancer patient.
TPS: TPS: Treatment planning system; EPID: Electronic portal imaging device; DRP: Dose reference point.

Discussion

The mean gamma analysis passing rate for phantom measurements was 97.2% and 98.3% for the patients with endometrial and cervical cancer, respectively. On the other hand, in vivo patient calculation results were 95.1% and 96.3% for endometrial and cervical cancer, respectively. The decrease in the passing rate may be due to the heterogeneity of the pelvic region which may have caused computational errors in the TPS. Since the pelvic region of the phantom consists only of bone and soft-tissue-equivalent materials, errors due to the calculation algorithm may therefore be fewer in the phantom. Another reason for observing this result may be the intrafractional variation due to organ deformation and/or movement. The intrafraction variations are smaller compared with the interfraction variations but are still of relevance in clinical practice. Although, patients are given detailed instructions to empty the rectum and fill the bladder and checked through CBCT, vaginal motion, and bladder and rectal volume changes can occur during treatment. To minimize the target motion, the use of intracavitary applicators was suggested for IMRT treatment of gynecological malignancies in clinical practice.[15,16] Cilla et al.[15] reported the agreement between the calculated and measured doses for this practice, where they performed the study with an ion chamber. As a future work, testing the accuracy of this practice can be performed with EPID in 3D.

In this study, we did not encounter any machinerelated or patient-related errors that may have adversely affected the results. The previous studies showed that in vivo EPID measurements have the potential to detect treatment delivery errors.[17-19] Mans et al.[17] reported 3D in vivo verification of 4337 patients that consisted of 1319 breast, 1018 prostate, 602 rectum, 543 head and neck, 454 lung, and 401 other cancer cases. Seventeen serious errors were detected among the treatment plans which were classified as patient anatomy (n=7), plan transfer (n=4), suboptimally tuned TPS parameter (n=2), accidental plan modification (n=2), failed delivery (n=1), and dosimetrically undeliverable plan (n=1). Other studies were also conducted to search the possible errors that could be detected by in vivo EPID measurements. [18,20] Previously, we[18] investigated the error detection capability of in vivo EPID measurements for the stereotactic body RT applications for prostate cancer. Our results showed that the EPID can detect the errors based on linear accelerator calibration, MLC positions, and patient anatomy.

One of the limitations of in vivo EPID-based dosimetry is the radiation field size. Since the maximum effective field size of the EPID at the isocenter is 26×26 cm2, the QA of the radiation fields above this size is not possible. In particular, in a patient with gynecological cancer that has para-aortic lymph node involvement and needs to be irradiated with extended field irradiation exceeds, this limitation for whom EPID-based dosimetry is not suitable. However, Kim et al.[21] designed a study using Halcyon® 2.0 (Varian Medical Systems, Palo Alto, CA, USA) machine to treat the extended fields using IMRT with dualisocenter in patients with gynecological cancer since Halcyon® 2.0 is capable of treating >28 cm treatment length using a dual isocenter. Their results showed that Halcyon® EPID-based in vivo dosimetry has the potential to function for complex IMRT and adaptive RT. They detected interfraction variations in random patterns depending on internal organ motion and source to skin distance change.

The advantage of EPID-based dosimetry over other systems is that it does not need extra time for application since the QA measurements are performed during treatment. In addition, QA can be easily applied in each fraction. If we assume that a pre-treatment QA for a patient takes 10 min, we saved approximately 200 min for 20 patients in the present study. It does not only save the physicist's time but also reduces on-time of the treatment machine.

Previously, few studies reported in vivo measurement results by the placement of dosimeters into the body cavities for pelvic RT which has the disadvantage of patient discomfort. The TLD and diodes were the most commonly used dosimeters in these studies. However, diode detectors are not suitable for IMRT or VMAT as the diode detector response exhibits orientation dependence. Diode sensitivity is reported to vary by up to 15% depending on gantry orientation.[22] Weber et al.[23] reported the results of patients with anal cancer undergoing in vivo dosimetry by TLD inserted at the center of the anal verge. The measured doses differed by an average of 6% compared to the TPS along the central axis. In general, the acceptance criterion is within ±10% for the TLD.[24] For the EPID-based system, this acceptance range is narrow. In the present study, the acceptance criterion of ±3% was used for point dose measurements with the EPID and all measurements were consistent with this criterion.

Conclusion

Peer-review: Externally peer-reviewed.

Conflict of Interest: All authors declared no conflict of interest.

Ethics Committee Approval: The study was approved by the Hacettepe University Non-Invasive Clinical Research Ethics Committee (no: 2022/05-36, date: 15/03/2022).

Financial Support: None declared.

Authorship contributions: Concept - Y.Y.; Design - Y.Y.; Supervision - Y.Y., S.Y.S.; Funding - None; Materials - S.Y.S., M.G., F.Y.; Data collection and/or processing - Y.Y., S.Y.S., M.G., F.Y.; Data analysis and/or interpretation - Y.Y., S.Y.S., M.G., F.Y.; Literature search - Y.Y., S.Y.S., M.G., F.Y.; Writing - Y.Y., S.Y.S., M.G., F.Y.; Critical review - Y.Y., S.Y.S., M.G., F.Y.

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