Vol 28, No 2 (2023)
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Assessment of dosimetric impact of interfractional 6D setup error in tongue cancer treated with IMRT and VMAT using daily kV-CBCT

Prashantkumar Shinde1, Anand Jadhav2, V. Shankar3, Sanjay J. Dhoble1
Rep Pract Oncol Radiother 2023;28(2):224-240.

Abstract

Background: This study aimed to evaluate the dosimetric influence of 6-dimensional (6D) interfractional setup error in tongue cancer treated with intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) using daily kilovoltage cone-beam computed tomography (kV-CBCT). 

Materials and methods: This retrospective study included 20 tongue cancer patients treated with IMRT (10), VMAT (10), and daily kV-CBCT image guidance. Interfraction 6D setup errors along the lateral, longitudinal, vertical, pitch, roll, and yaw axes were evaluated for 600 CBCTs. Structures in the planning CT were deformed to the CBCT using deformable registration. For each fraction, a reference CBCT structure set with no rotation error was created. The treatment plan was recalculated on the CBCTs with the rotation error (RError), translation error (TError), and translation plus rotation error (T+RError). For targets and organs at risk (OARs), the dosimetric impacts of RError, TError, and T+RError were evaluated without and with moderate correction of setup errors.

Results: The maximum dose variation ΔD (%) for D98% in clinical target volumes (CTV): CTV-60, CTV-54, planning target volumes (PTV): PTV-60, and PTV-54 was –1.2%, –1.9%, –12.0%, and –12.3%, respectively, in the T+RError without setup error correction. The maximum ΔD (%) for D98% in CTV-60, CTV-54, PTV-60, and PTV-54 was –1.0%, –1.7%, –9.2%, and –9.5%, respectively, in the T+RError with moderate setup error correction. The dosimetric impact of interfractional 6D setup errors was statistically significant (p < 0.05) for D98% in CTV-60, CTV-54, PTV-60, and PTV-54.

Conclusions: The uncorrected interfractional 6D setup errors could significantly impact the delivered dose to targets and OARs in tongue cancer. That emphasized the importance of daily 6D setup error correction in IMRT and VMAT. 

research paper

Reports of Practical Oncology and Radiotherapy

2023, Volume 28, Number 2, pages: 224–240

DOI: 10.5603/RPOR.a2023.0020

Submitted: 12.01.2023

Accepted: 29.03.2023

© 2023 Greater Poland Cancer Centre.

Published by Via Medica.

All rights reserved.

e-ISSN 2083–4640

ISSN 1507–1367

Assessment of dosimetric impact of interfractional 6D setup error in tongue cancer treated with IMRT and VMAT using daily kV-CBCT

Prashantkumar Shinde1Anand Jadhav2V. Shankar3Sanjay J. Dhoble1
1Department of Physics, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, India
2Department of Radiation Oncology, Sir H N Reliance Foundation Hospital and Research Centre, Mumbai, India
3Department of Radiation Oncology, Apollo Cancer Center, Chennai, India

Address for correspondence: Prashantkumar Shinde, M.Sc., D.R.P., Department of Physics, Rashtrasant Tukadoji Maharaj Nagpur University, Amravati Road, Nagpur 440033, India, tel: (+91) 9923472316; e-mail: pk.shinde16@gmail.com

This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially

Abstract
Background: This study aimed to evaluate the dosimetric influence of 6-dimensional (6D) interfractional setup error in tongue cancer treated with intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) using daily kilovoltage cone-beam computed tomography (kV-CBCT).
Materials and methods: This retrospective study included 20 tongue cancer patients treated with IMRT (10), VMAT (10), and daily kV-CBCT image guidance. Interfraction 6D setup errors along the lateral, longitudinal, vertical, pitch, roll, and yaw axes were evaluated for 600 CBCTs. Structures in the planning CT were deformed to the CBCT using deformable registration. For each fraction, a reference CBCT structure set with no rotation error was created. The treatment plan was recalculated on the CBCTs with the rotation error (RError), translation error (TError), and translation plus rotation error (T+RError). For targets and organs at risk (OARs), the dosimetric impacts of RError, TError, and T+RError were evaluated without and with moderate correction of setup errors.
Results: The maximum dose variation ΔD (%) for D98% in clinical target volumes (CTV): CTV-60, CTV-54, planning target volumes (PTV): PTV-60, and PTV-54 was –1.2%, –1.9%, –12.0%, and –12.3%, respectively, in the T+RError without setup error correction. The maximum ΔD (%) for D98% in CTV-60, CTV-54, PTV-60, and PTV-54 was –1.0%, –1.7%, –9.2%, and –9.5%, respectively, in the T+RError with moderate setup error correction. The dosimetric impact of interfractional 6D setup errors was statistically significant (p < 0.05) for D98% in CTV-60, CTV-54, PTV-60, and PTV-54.
Conclusions: The uncorrected interfractional 6D setup errors could significantly impact the delivered dose to targets and OARs in tongue cancer. That emphasized the importance of daily 6D setup error correction in IMRT and VMAT.
Key words: dosimetric impact; interfractional 6D setup error; kV-CBCT; tongue cancer; head and neck cancer; IMRT; VMAT
Rep Pract Oncol Radiother 2023;28(2):224–240

Introduction

Tongue cancer is one of the most common human papilloma virus (HPV)-attributed head and neck malignant tumors globally [1]. Modern, state-of-the-art radiation therapy techniques, such as intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), play a vital role in managing head and neck cancer. Both IMRT and VMAT deliver precise and highly conformal doses to the targets while sparing the surrounding organs at risk (OARs) [2–3]. A multicentric randomized trial found that IMRT and VMAT had better tumor control and lower toxicity than 2D and 3D RT techniques, which was corroborated by two subsequent meta-analyses and dosimetric investigations [4–6]. For IMRT and VMAT, the highly conformal dose distribution to the target with rapid dose falloff outside the target perimeter needs extreme precision in target localization to get the optimal benefit [7, 8]. 3D image guidance techniques used in IMRT and VMAT allow for greater precision in the intended dose delivery [8–13]. Even with the rigid immobilization, target localization and setup error persist and could have an adverse dosimetric effects [14–16]. The magnitudes of interfractional setup errors in head and neck cancer are significant [13, 17–21]. They have substantial dosimetric effects on delivered doses to targets and OARs. Previous studies found that interfractional translational and rotational errors significantly alter the delivered dose to target volumes and OARs [22–31]. Many such studies have employed various methods to mimic the dosimetric impact of setup errors. These methods include dose simulation on planning computed tomography (pCT), cone-beam CT (CBCT), and dose accumulation using deformable image registration of pCT and CBCT [22–32]. Most previous studies simulated and evaluated the dosimetric impact of interfractional setup errors on pCT with weekly or lower imaging frequencies of setup verification [22–29]. The dosimetric impact of 6-dimensional (6D) interfractional setup errors in head and neck cancer has been studied in previous studies. In these studies, the dosimetric impact on pCT was based on the assumption that there was no geometric variation over the entire treatment course [22, 24, 27, 28, 30]. However, interfractional geometric variation could occur throughout the treatment [33, 34]. The CBCT acquired for pretreatment setup verification provides the actual patient volumes at the treatment fraction. CBCT-based dose reconstruction could provide the actual dose delivered to the patient in the treatment fraction. Previous studies have reported on the feasibility and accuracy of CBCT for treatment dose simulation [35–42].

Evaluation of the dosimetric impact of 6D interfractional setup errors on verification CBCT is highly relevant as CBCT characterizes the actual patient’s volumes at the treatment. Similarly, Otsuka et al. evaluated the dosimetric impact of parotid and mandible rotation in oropharyngeal cancer using CBCT dose reconstruction. However, the dosimetric impact was evaluated with a limited CBCT dataset [31]. Most radiotherapy clinics perform verification imaging for the first three days and then weekly or less frequently (moderate setup error correction) for IMRT and VMAT [20, 25, 27–29, 31]. However, in tongue (head and neck) cancer, it is important to use daily CBCT to see how the daily interfractional setup error affects the dose.

There is no comprehensive study evaluating how 6D interfractional setup errors affect the dose in tongue cancer patients utilizing daily kilovoltage CBCT dose reconstruction. This study aimed to evaluate the dosimetric impact of daily rotational, translational, and translational plus rotational (6D) errors on target volumes and OARs by using daily kilovoltage CBCT (kV-CBCT).

Materials and methods

Patient characteristics

This retrospective dosimetric study included 20 patients diagnosed with squamous cell carcinoma of the tongue (Stage = T1N0M0–T2N1M0). The study population consisted of fifteen males and five females with a median age of 61 years (range 35–72). Patients underwent definitive radiation therapy by IMRT (10) and VMAT (10) with daily kV-CBCT image guidance. The PerfectPitch 6D robotic couch on the Varian TrueBeam STx linear accelerator was used to correct the setup errors.

Patient simulation and treatment planning

Patients were simulated supine and immobilized with five-clamp head and neck thermoplastic masks with individualized low-density headrests (Orfit Industries, Wijnegem, Belgium). Patients were advised to keep their tongues straight up and not swallow to minimize tongue dislocation during treatment. The pCT scans were acquired on a Biograph mCT flow helical positron emission tomography/computed tomography (PET-CT) scanner (Siemens Medical Systems, Erlangen, Germany) with a 3 mm slice thickness and transferred to the Eclipse treatment planning system (TPS) (v. 13.7, Varian Medical System, Palo Alto, United States). The planning target volume (PTV) PTV-60, the intermediate-risk PTV, and PTV-54, the low-risk PTV, were prescribed with 60 Gy and 54 Gy in 30 fractions, respectively. PTV was prescribed to receive a minimum of 95% dose and a maximum of 2% volume more than 107% dose. The maximum dose constraint prescribed for the brainstem, spinalcord, and mandible was 54 Gy, 45 Gy, and 65 Gy. The mean dose constraints prescribed for the parotids and the larynx were 26 Gy and 45 Gy, respectively. Treatment plans with 6MV photon energy were optimized for IMRT (7–9 fields) and VMAT (2–3 co-planer full arcs) treatment techniques with a 5 mm target margin in TPS. Dose calculation was done with an analytical anisotropic algorithm (AAA) using a 2.5 mm dose grid.

Image acquisition and evaluation of interfractional 6D setup error

kV-CBCT imaging was used for pretreatment patient positional verification for each fraction. The kV-CBCTs were acquired with an onboard imaging (OBI) system (Varian Medical Systems, Palo Alto, United States) on the TrueBeam STx Linac. The CBCT images were acquired in full-fan mode with 100 kV and 270 mAs in full trajectory. All the images were acquired with a 3 mm slice thickness and had a sufficient scan length to encompass the full target volume. CBCT and pCT images were registered based on bony structure and soft-tissue contrast with the registration software. The 6D setup errors were assessed in the lateral (X), longitudinal (Y), and vertical (Z) principal translation axes, as well as the pitch (RX), roll (RY), and yaw (RZ) rotation axes along the principal translation axes. The 6D setup errors of all patients with 600 kV-CBCTs were assessed and used for the evaluation of the dosimetric influence of uncorrected 6D setup errors.

Dose metrics evaluated for target volumes and OARs

The dosimetric influence of rotation error (RError), translation error (TError) and 6D translation plus rotation error (T+RError) was evaluated for clinical target volumes (CTV) CTV-60, CTV-54, PTV-60, and PTV-54 with a dose metric of D98% (dose to 98% of volume), D95%, D2%, and D0.035cc (dose to 0.035 cc volume, a near-maximum dose) on the dose-volume histogram (DVH). The OARs: spinalcord, brainstem, and mandible were evaluated for dose metrics of D1cc and D0.035cc. left parotid, right parotid, and larynx were evaluated for the dose metrics Dmean (mean dose in volume) and D50%.

Treatment plan simulation with 6D setup errors using kV-CBCT

The pCT structure set was deformed to CBCT using Varian’s demons deformable image registration (DIR) implemented in SmartAdapt (SA) (v.13.7, Varian Medical System, Palo Alto, CA, United States) in Eclipse TPS. A radiation oncologist evaluated the deformed structures on CBCT for accuracy and integrity. Pretreatment CBCT images inherently contain translation and rotation setup errors if they exist in the treatment setup. Similarly, CBCT images contain the interfraction geometric (external as well as internal organ) variation if it exists. However, we aimed to investigate the influence of only uncorrected setup errors on the delivered doses of the treatment plans. To eliminate the effect of geometric variation (external body) on evaluating the dosimetric influence of setup errors, a reference CBCT structure set (CBCT_REF) without 6D setup errors was generated on pre-treatment CBCT. However, the internal geometric variations were accounted for in the CBCT structure set. The CBCT structures were mapped (copied) on pCT with rigid registration and re-mapped back onto CBCT from pCT without rotational correction in the rigid registration. The workflow is illustrated in Figure 1. The original treatment plan on pCT (Fig. 2AB) was recalculated using CBCT_REF, utilizing beam parameters, monitor units, and fluence maps from the original plan. A previously evaluated and validated HU to ED conversion curve for head and neck CBCT in our institute was used for dose calculation [42]. This plan without 6D setup errors was referred to as the reference plan (Ref). The treatment plan R with rotation error (RError) alone was simulated on pretreatment CBCT without translation error (TError), illustrated in Figures 2CD (Example). The treatment plan T+R with 6D translation plus rotation error (T+RError) was simulated on a pretreatment CBCT with T+RError. The treatment plan T with TError alone was simulated on the CBCT_REF structure set.

157545.png
Figure 1. Workflow to deform planning computed tomography (pCT) structure-set to cone-beam computed tomography (CBCT) and to generate CBCT_REF structure set
157558.png
Figure 2. Original treatment plan dose distribution for planning target volume (PTV): PTV-60 and PTV-54 on (A) axial computed tomography (CT) image and (B) coronal CT image, and recalculated dose distribution with rotational error for PTV-60 and PTV-54 on (C) axial cone-beam computed tomography (CBCT) image and (D) coronal CBCT image, for a single fraction.

The dosimetric influence of RError, TError, and T+RError was evaluated by comparing the reference plan (Ref) with RError (R), TError (T), and T+RError (T+R) plans on CBCT. For each fraction, the percentage dose variation in the RError plan (δDR (%)), TError plan (δDT (%)), and T+RError plan (δDT+R (%)) in the evaluated target volumes and OARs for the corresponding dose metrics were calculated.

The mean percentage dose variation ΔDR (%), ΔDT (%), and ΔDT+R (%) due to RError, TError, and T+RError, respectively, for all evaluated structures and the corresponding dose metric of all patients were calculated. The absolute dose variation in Gray (Gy) owing to RError, TError, and T+RError in original treatment plan on pCT was calculated by applying the corrections with % dose variation δDR (%), δDT (%), and δDT+R (%) to the DVH of the corresponding structures and dose metrics in each fraction of the treatment plan. The mean absolute dose variation in ΔDR (Gy), ΔDT (Gy), and ΔDT+R (Gy) due to RError, TError, and T+RError, respectively, for the corresponding evaluated structures and dose metrics was calculated for all patients. The dosimetric influence of 6D setup error was evaluated for no setup error correction and moderate setup error correction (first three days and weekly once thereafter) approach.

Statistical analysis

The mean absolute dose DP (Gy) of the evaluated structures for each dose metric (e.g., CTV-60 for dose metrics D98%, D95%, D2%, and D0.03cc) in the original treatment plan of 20 patients was compared to the mean absolute doses DR (Gy), DT (Gy), and DT+R (Gy) in the RError plan, TError plan, and T+RError plan, respectively. Statistical analysis was done in Microsoft Excel. The two-tailed paired t-test was used to test the hypothesis that there was no difference between the DP (Gy) and DR (Gy), DP (Gy) and DT (Gy), and DP (Gy) and DT+R (Gy) for the evaluated structures and dose metrics in 20 patients with α = 0.05.

Results

Assessment of the 6D setup error

A total of 600 pretreatment kV-CBCTs were evaluated for 6D setup error analysis. The Van Herk PTV margin (Margin = 2.5 Σ+0.7 σ) [43] for population systematic (Σ) and random (σ) error was 4.7 mm, 3.9 mm, and 4.5 mm along the X, Y, and Z axes, respectively. The single fraction maximum error was 7 mm, 7 mm, 8 mm, 3.00, 2.90, and 2.90 along the X, Y, Z, RX, RY, and RZ axes, respectively.

Dosimetric influence of the 6D setup error

Figure 3 depicts a single fraction DVH comparison for patient 1 between a reference plan (Ref) with no setup error and plan ‘R’ with RError, plan ‘T’ with TError, and plan ‘T+R’ with 6D T+RError. The dose variation in the target volume and OARs due to RError, TError, and T+RError is realized in Figures 3A–C, respectively. The mean % dose variation ΔDR (%), ΔDT (%), and ΔDT+R (%) in targets and OARs for the corresponding evaluated dose metrics with no setup error correction in all fractions and with a moderate setup error correction approach are summarized in Table 1.

157678.png
Figure 3. Dose volume histogram comparison for a single fraction of patient-1 for (A) reference plan (Ref) and rotational error plan (R), (B) reference plan (Ref) and translational error plan (T), and (c) reference plan (Ref) and translational plus rotational error plan (T+R). DVH color: clinical target volume (CTV): CTV-60 (dark blue), CTV-54 (cyan), planning target volume (PTV): PTV-60 (pink),PTV-54 (orange), parotid-right, and parotid-left (yellow), brainstem (brown), spinalcord (cyan), mandible and larynx (dark brown). Dose volume histogram (DVH) marker: reference plan (triangle) and setup error plan (square)
Table 1. The overall mean percentage dose variation in targets and organs at risk (OARs) for the corresponding evaluated dose metrics in 20 patients with no setup error correction and moderate setup error correction approach

With no setup error correction

With moderate setup error correction

ROI

Doseindex

ΔDR (%)

Mean ± SD

ΔDT (%)

Mean ± SD

ΔDT+R (%)

Mean ± SD

ΔDR (%)

Mean ± SD

ΔDT (%)

Mean ± SD

ΔDT+R (%)

Mean ± SD

CTV-60

D98%

–0.3 ± 0.2

–0.4 ± 0.3

–0.6 ± 0.3

–0.2 ± 0.1

–0.3 ± 0.2

–0.5 ± 0.3

D95%

–0.1 ± 0.1

–0.3 ± 0.2

–0.4 ± 0.3

–0.1 ± 0.1

–0.2 ± 0.2

–0.3 ± 0.2

D2%

0.2 ± 0.1

0.3 ± 0.3

0.5 ± 0.3

0.1 ± 0.1

0.2 ± 0.3

0.3 ± 0.3

D0.035cc

0.6 ± 0.9

0.7 ± 0.6

1.3 ± 1.2

0.4 ± 0.6

0.6 ± 0.4

1.1 ± 1.0

CTV-54

D98%

–0.2 ± 0.4

–0.4 ± 0.6

–0.6 ± 0.5

–0.1 ± 0.3

–0.3 ± 0.5

–0.4 ± 0.5

D95%

–0.2 ± 0.5

–0.2 ± 0.5

–0.4 ± 0.5

–0.1 ± 0.3

–0.2 ± 0.4

–0.3 ± 0.4

D2%

0.4 ± 0.5

0.7 ± 0.6

1.1 ± 0.6

0.3 ± 0.4

0.5 ± 0.5

0.8 ± 0.4

D0.035cc

0.7 ± 1.1

1.2 ± 0.8

1.9 ± 0.7

0.5 ± 0.8

0.8 ± 0.7

1.4 ± 0.5

PTV-60

D98%

–0.6 ± 0.5

–4.0 ± 2.6

–4.5 ± 2.8

–0.5 ± 0.4

–3.0 ± 2.0

–3.4 ± 2.2

D95%

–0.3 ± 0.3

–2.5 ± 1.8

–2.7 ± 2.0

–0.2 ± 0.2

–1.9 ± 1.4

–2.1 ± 1.5

D2%

0.2 ± 0.1

0.3 ± 0.3

0.5 ± 0.3

0.1 ± 0.1

0.2 ± 0.3

0.3 ± 0.2

D0.035cc

1.0 ± 0.9

1.4 ± 1.3

2.3 ± 1.5

0.7 ± 0.6

1.1 ± 0.9

1.7 ± 1.2

PTV-54

D98%

–0.6 ± 0.5

–4.7 ± 3.1

–5.4 ± 3.9

–0.4 ± 0.4

–3.5 ± 2.5

–4.0 ± 2.5

D95%

–0.4 ± 0.4

–2.4 ± 2.0

–2.7 ± 2.0

–0.2 ± 0. 3

–1. 8 ± 1.6

–2.0 ± 1.7

D2%

0.4 ± 0.5

0.8 ± 0.6

1.2 ± 0.4

0.3 ± 0.4

0. 5 ± 0.5

0.9 ± 0.3

D0.035cc

1.0 ± 1.2

1.7 ± 1.9

2.5 ± 1.4

0.7 ± 0.9

1.2 ± 1.5

1.8 ± 1.1

Spinalcord

D1cc

0.5 ± 1.4

0.4 ± 2.2

0.9 ± 2.2

0.5 ± 1.1

0.2 ± 2.1

0.7 ± 1.9

D0.035cc

0.3 ± 0.4

1.2 ± 2.6

1.6 ± 2.8

0.2 ± 0.3

1.1 ± 2.3

1.3 ± 2.4

Brainstem

D1cc

–0.3 ± 0.7

–1.5 ± 4.1

–1.9 ± 4.2

–0.2 ± 0.6

–1.0 ± 3.1

–1.2 ± 3.2

D0.035cc

–0.5 ± 0.7

–2.4 ± 3.3

–3.0 ± 3.1

–0.4 ± 0.6

–0.2 ± 2.5

–2.4 ± 2.3

Left Parotid

Dmean

0.4 ± 2.2

5.5 ± 6.1

5.7 ± 6.2

0.4 ± 1.1

4.4 ± 4.6

4.7 ± 5.0

D50%

–0.8 ± 4.7

10.6 ± 15.2

10.1 ± 15.9

–0.2 ± 3.6

7.5 ± 10.9

7.7 ± 12.0

Right Parotid

Dmean

1.7 ± 2.5

0.3 ± 8.3

1.7 ± 9.2

1.1 ± 2.0

–0.1 ± 6.7

1.0 ± 7.4

D50%

2.3 ± 5.1

–0.7 ± 10.8

2.6 ± 13.3

2.8 ± 5.0

–0.2 ± 7.7

2.4 ± 10.8

Larynx

Dmean

0.2 ± 0.5

–0.4 ± 2.1

–0.3 ± 2.0

0.1 ± 0.4

–0.5 ± 1.6

–0.4 ± 1.5

D50%

–0.0 ± 0.4

–0.5 ± 2.0

–0.4 ± 2.0

0.1 ± 0.3

–0.4 ± 1.6

–0.3 ± 1.6

Mandible

D1cc

–0.2 ± 1.2

1.0 ± 1.4

0.7 ± 0.6

–0.4 ± 1.2

0.7 ± 1.4

0.3 ± 0.8

D0.035cc

0.6 ± 0.5

1.1 ± 1.0

1.4 ± 0.9

0.2 ± 0.3

0.6 ± 08

0.8 ± 0.9

The box and whisker plot in Figure 4 for CTV-60, CTV-54, PTV-60 and PTV-54, and in Figure 5 for Spinal Cord and Brainstem, Left Parotid and Right Parotid, and for Larynx and Mandible depict the percentage dose variation ΔD (%) in the RError plan (R), TError plan (T), and 6D T+RError plan (T+R) on CBCT with respect to the reference plan (Ref) on CBCT_REF for the corresponding evaluated dose metrics with no setup error correction (NC) and moderate setup error correction (MC) in few fractions.

157691.png
Figure 4. Box and whisker plot for percentage dose variation ΔD (%) in rotational error (R), translational error (T), and translational plus rotational error (T+R) plans with no correction (NC) and moderate correction (MC) of setup errors for D98%, D95%, D2%, and D0.035cc in clinical target volume (CTV): (A) CTV-60, (B) CTV-54, and planning target volume (PTV) (C) PTV-60, and (D) PTV-54. The cross represents the mean, the line inside the box represents the median, the bottom of the box represents the 25% quartile, the top of the box represents the 75% quartile, the bottom whisker represents the minimum value, the top whisker represents the maximum value, and the dots represent the outlier
157703.png
Figure 5. Box and whisker plot for percentage dose variation ΔD (%) in rotational error (R), translational error (T), and translational plus rotational error (T+R) plans with no correction (NC) and moderate correction (MC) of setup errors (A) for D1cc and D0.035cc, in the spinalcord (SC) and brainstem (BS), (B) for Dmean and D50% in the parotid-left (PL) and parotid-right (PR), and (C) for Dmean and D50% in the larynx (LAR), and for D1cc and D0.035cc in the mandible (MAN). The cross represents the mean, the line inside the box represents the median, the bottom of the box represents the 25% quartile, the top of the box represents the 75% quartile, the bottom whisker represents the minimum value, the top whisker represents the maximum value, and the dots represent the outlier

For the no setup error correction and moderate setup error correction approaches, respectively, Table 2 and Table 3 summarized the absolute mean dose DP (Gy) in the original treatment plan and the DR (Gy), DT (Gy), and DT+R (Gy) in the RError, TError, and T+RError plans, respectively, for all CTVs, PTVs, and OARs with the corresponding evaluated dose metrics across all 20 patients. Similarly, Tables 4 and Table 5 summarized the mean percentage dose variation ΔDR (%), ΔDT (%), and ΔDT+R (%) for IMRT and VMAT plans in CTVs, PTVs, and OARs for the corresponding evaluated dose metrics with no setup error correction and moderate setup error correction approaches, respectively.

Table 2. Mean dose of the target and organ at risk (OAR) volumes for the corresponding evaluated dose metrics in the original treatment plan and setup error plans for 20 patients with no setup error correction approach

ROI

Dose-index

DP [Gy]

Mean ± SD

DR [Gy]

Mean ± SD

p*

DT [Gy]

Mean ± SD

p*

DT+R [Gy]

Mean ± SD

p*

CTV-60

D98%

59.15 ± 0.47

58.99 ± 0.44

< 0.05

58.89 ± 0.51

< 0.05

58.77 ± 0.50

< 0.05

D95%

59.48 ± 0.52

59.40 ± 0.52

< 0.05

59.28 ± 0.51

< 0.05

59.22 ± 0.51

< 0.05

D2%

62.50 ± 0.57

62.63 ± 0.54

< 0.05

62.70 ± 0.67

< 0.05

62.79 ± 0.65

< 0.05

D0.035cc

63.84 ± 0.52

64.23 ± 0.57

< 0.05

64.30 ± 0.56

< 0.05

64.69 ± 0.72

< 0.05

CTV-54

D98%

53.56 ± 0.77

53.46 ± 0.85

0.136

53.35 ± 0.75

< 0.05

53.26 ± 0.78

< 0.05

D95%

53.79 ± 0.75

53.69 ± 0.84

0.214

53.68 ± 0.74

0.173

53.59 ± 0.79

< 0.05

D2%

56.08 ± 0.89

56.27 ± 0.82

< 0.05

56.47 ± 1.13

< 0.05

56.68 ± 1.03

< 0.05

D0.035cc

56.69 ± 0.92

57.09 ± 0.92

< 0.05

57.36 ± 1.17

< 0.05

57.76 ± 0.96

< 0.05

PTV-60

D98%

57.97 ± 0.41

57.62 ± 0.54

< 0.05

55.64 ± 1.43

< 0.05

55.34 ± 1.58

< 0.05

D95%

58.77 ± 0.41

58.58 ± 0.49

< 0.05

57.32 ± 1.02

< 0.05

57.16 ± 1.11

< 0.05

D2%

62.55 ± 0.58

62.68 ± 0.55

< 0.05

62.75 ± 0.64

< 0.05

62.86 ± 0.64

< 0.05

D0.035cc

64.38 ± 0.62

65.01 ± 0.88

< 0.05

65.26 ± 0.76

< 0.05

65.85 ± 1.06

< 0.05

PTV-54

D98%

52.96 ± 0.57

52.65 ± 0.63

< 0.05

50.46 ± 1.57

< 0.05

50.12 ± 1.61

< 0.05

D95%

53.45 ± 0.63

53.26 ± 0.70

< 0.05

52.17 ± 1.08

< 0.05

51.99 ± 1.14

< 0.05

D2%

56.30 ± 0.92

56.55 ± 0.82

< 0.05

56.76 ± 1.15

< 0.05

57.00 ± 1.02

< 0.05

D0.035cc

58.32 ± 1.23

58.87 ± 1.12

< 0.05

59.31 ± 2.02

< 0.05

59.79 ± 1.61

< 0.05

Spinalcord

D1cc

33.65 ± 2.59

33.82 ± 2.48

0.200

33.82 ± 3.14

0.440

33.98 ± 3.05

0.151

D0.035cc

36.45 ± 2.32

36.57 ± 2.41

< 0.05

36.93 ± 2.99

0.108

37.07 ± 3.09

0.061

Brainstem

D1cc

26.58 ± 9.48

26.47 ± 9.70

0.061

26.19 ± 9.70

0.164

26.05 ± 9.57

0.091

D0.035cc

31.91 ± 9.88

31.73 ± 9.76

< 0.05

31.14 ± 9.61

< 0.05

30.93 ± 9.48

< 0.05

Left parotid

Dmean

30.90 ± 9.41

30.92 ± 9.52

0.895

32.32 ± 9.03

< 0.05

32.47 ± 9.32

< 0.05

D50%

28.61 ± 16.44

28.47 ± 16.57

0.581

30.93 ± 16.9

0.132

30.96 ± 17.3

0.143

Right parotid

Dmean

27.43 ± 3.22

27.88 ± 3.16

< 0.05

27.46 ± 3.40

0.969

27.81 ± 3.45

0.605

D50%

22.73 ± 6.20

23.19 ± 6.09

0.168

22.38 ± 5.75

0.598

23.08 ± 5.85

0.687

Larynx

Dmean

44.96 ± 3.81

45.04 ± 3.94

0.277

44.79 ± 3.83

0.535

44.83 ± 3.93

0.595

D50%

44.87 ± 5.24

44.87 ± 5.36

0.988

44.67 ± 5.33

0.402

44.71 ± 5.42

0.506

Mandible

D1cc

61.92 ± 0.52

61.78 ± 0.66

0.518

62.56 ± 1.09

< 0.05

62.36 ± 0.46

< 0.05

D0.035cc

62.87 ± 0.64

63.21 ± 0.53

< 0.05

63.57 ± 0.80

< 0.05

63.77 ± 0.70

< 0.05

Table 3. Mean dose of the target and organ at risk (OAR) volumes for the corresponding evaluated dose metrics in the original treatment plan and setup error plans for 20 patients with moderate setup error correction approach

ROI

Dose-index

DP [Gy]

Mean ± SD

DR [Gy]

Mean ± SD

p*

DT [Gy]

Mean ± SD

P*

DT+R [Gy]

Mean ± SD

p*

CTV-60

D98%

59.13 ± 0.47

59.03 ± 0.44

< 0.05

58.94 ± 0.50

< 0.05

58.85 ± 0.48

< 0.05

D95%

59.47 ± 0.52

59.42 ± 0.52

< 0.05

59.32 ± 0.51

< 0.05

59.28 ± 0.51

< 0.05

D2%

62.53 ± 0.56

62.61 ± 0.55

< 0.05

62.68 ± 0.62

< 0.05

62.72 ± 0.62

< 0.05

D0.035cc

63.84 ± 0.52

64.11 ± 0.47

< 0.05

64.20 ± 0.52

< 0.05

64.53 ± 0.60

< 0.05

CTV-54

D98%

53.56 ± 0.77

53.48 ± 0.82

0.160

53.40 ± 0.77

0.142

53.33 ± 0.80

< 0.05

D95%

53.79 ± 0.75

53.72 ± 0.81

0.224

53.69 ± 0.73

0.209

53.63 ± 0.77

< 0.05

D2%

56.08 ± 0.89

56.23 ± 0.83

< 0.05

56.35 ± 1.07

< 0.05

56.52 ± 0.99

< 0.05

D0.035cc

56.69 ± 0.92

57.00 ± 0.88

< 0.05

57.16 ± 1.12

< 0.05

57.47 ± 0.95

< 0.05

PTV-60

D98%

57.97 ± 0.41

57.71 ± 0.50

< 0.05

56.22 ± 1.11

< 0.05

56.00 ± 1.22

< 0.05

D95%

58.77 ± 0.41

58.63 ± 0.46

< 0.05

57.67 ± 0.81

< 0.05

57.55 ± 0.88

< 0.05

D2%

62.55 ± 0.58

62.65 ± 0.56

< 0.05

62.69 ± 0.62

< 0.05

62.78 ± 0.62

< 0.05

D0.035cc

64.38 ± 0.62

64.81 ± 0.75

< 0.05

65.07 ± 0.64

< 0.05

65.47 ± 0.86

< 0.05

PTV-54

D98%

52.96 ± 0.57

52.74 ± 0.60

< 0.05

51.12 ± 1.23

< 0.05

50.87 ± 1.27

< 0.05

D95%

53.45 ± 0.63

53.31 ± 0.68

< 0.05

52.50 ± 0.93

< 0.05

52.36 ± 0.98

< 0.05

D2%

56.30 ± 0.92

56.50 ± 0.84

< 0.05

56.63 ± 1.10

< 0.05

56.81 ± 1.00

< 0.05

D0.035cc

58.32 ± 1.23

58.72 ± 1.10

< 0.05

59.05 ± 1.82

< 0.05

59.39 ± 1.50

< 0.05

Spinalcord

D1cc

33.65 ± 2.59

33.82 ± 2.46

0.124

33.79 ± 3.08

0.506

33.94 ± 2.96

0.122

D0.035cc

36.45 ± 2.32

36.52 ± 2.38

< 0.05

36.86 ± 2.87

0.117

36.95 ± 2.94

0.007

Brainstem

D1cc

26.58 ± 9.48

27.05 ± 10.17

0.008

26.93 ± 10.29

0.354

26.83 ± 10.21

0.241

D0.035cc

31.91 ± 9.88

31.77 ± 9.77

< 0.05

31.31 ± 9.67

< 0.05

31.15 ± 9.54

< 0.05

Left parotid

Dmean

30.90 ± 9.41

30.93 ± 9.48

0.317

31.95 ± 9.08

< 0.05

32.10 ± 9.32

< 0.05

D50%

28.61 ± 16.44

28.45 ± 16.49

1.000

30.00 ± 16.42

0.181

30.16 ± 16.68

0.178

Right parotid

Dmean

27.43 ± 3.22

27.81 ± 3.21

0.116

27.42 ± 3.20

0.716

27.71 ± 3.25

0.882

D50%

22.73 ± 6.20

23.01 ± 6.15

0.117

22.23 ± 5.68

0.546

22.77 ± 5.75

0.752

Larynx

Dmean

44.96 ± 3.81

45.05 ± 3.93

0.447

44.80 ± 3.79

0.386

44.85 ± 3.89

0.463

D50%

44.87 ± 5.24

44.88 ± 5.35

0.270

44.67 ± 5.28

0.541

44.72 ± 5.37

0.713

Mandible

D1cc

61.92 ± 0.52

59.92 ± 4.23

0.257

60.62 ± 4.75

0.124

62.37 ± 4.59

0.231

D0.035cc

62.87 ± 0.64

61.82 ± 3.30

0.075

62.07 ± 3.50

< 0.05

62.18 ± 3.59

< 0.05

Table 4. The overall mean percentage dose variation in targets and organ at risk (OARs) for 10 intensity-modulated radiation therapy (IMRT) and 10 volumetric modulated arc therapy (VMAT) patients for corresponding dose metrics with no setup error correction approach

ROI

Dose-index

IMRT (N=10)

VMAT (N=10)

ΔDR (%)

Mean ± SD

ΔDT (%)

Mean ± SD

ΔDT+R (%)

Mean ± SD

ΔDR (%)

Mean ± SD

ΔDT (%)

Mean ± SD

ΔDT+R (%)

Mean ± SD

CTV-60

D98%

–0.34 ± 0.16

–0.36 ± 0.27

–0.64 ± 0.41

–0.20 ± 0.12

–0.52 ± 0.22

–0.64 ± 0.28

D95%

–0.18 ± 0.06

–0.25 ± 0.25

–0.41 ± 0.32

–0.10 ± 0.10

–0.40 ± 0.12

–0.46 ± 0.16

D2%

0.15 ± 0.15

0.43 ± 0.33

0.57 ± 0.39

0.24 ± 0.09

0.19 ± 0.09

0.35 ± 0.14

D0.035cc

0.53 ± 0.81

0.55 ± 0.47

1.07 ± 0.92

0.70 ± 1.07

0.88 ± 0.68

1.59 ± 1.538

CTV-54

D98%

0.04 ± 0.08

–0.71 ± 0.66

–0.69 ± 0.66

–0.41 ± 0.48

–0.06 ± 0.32

–0.41 ± 0.38

D95%

0.05 ± 0.06

–0.51 ± 0.47

–0.47 ± 0.47

–0.41 ± 0.60

0.10 ± 0.29

–0.29 ± 0.52

D2%

0.20 ± 0.21

0.76 ± 0.52

1.00 ± 0.57

0.51 ± 0.68

0.62 ± 0.73

1.15 ± 0.56

D0.035cc

0.30 ± 0.27

1.39 ± 0.53

1.74 ± 0.77

1.13 ± 1.42

0.95 ± 1.05

2.03 ± 0.61

PTV-60

D98%

–0.72 ± 0.58

–4.32 ± 3.59

–4.82 ± 3.78

–0.50 ± 0.43

–3.71 ± 1.59

–4.24 ± 1.65

D95%

–0.41 ± 0.36

–2.74 ± 2.47

–3.03 ± 2.64

–0.25 ± 0.27

–2.21 ± 1.09

–2.44 ± 1.09

D2%

0.16 ± 0.14

0.50 ± 0.33

0.62 ± 0.37

0.25 ± 0.09

0.13 ± 0.10

0.36 ± 0.11

D0.035cc

0.93 ± 0.95

0.98 ± 1.53

1.75 ± 1.36

1.04 ± 0.94

1.78 ± 0.85

2.83 ± 1.56

PTV-54

D98%

–0.46 ± 0.19

–6.02 ± 3.76

–6.58 ± 3.77

–0.71 ± 0.71

–3.41 ± 1.85

–4.14 ± 2.12

D95%

–0.20 ± 0.12

–3.28 ± 2.45

–3.53 ± 2.49

–0.50 ± 0.58

–1.49 ± 0.73

–1.94 ± 1.09

D2%

0.26 ± 0.14

0.84 ± 0.44

1.12 ± 0.43

0.63 ± 0.61

0.76 ± 0.76

1.35 ± 0.27

D0.035cc

0.60 ± 0.61

2.18 ± 1.65

2.56 ± 1.71

1.30 ± 1.64

1.16 ± 2.22

2.45 ± 1.22

Spinalcord

D1cc

–0.16 ± 0.41

–0.23 ± 2.17

–0.27 ± 2.27

1.23 ± 1.69

1.03 ± 2.22

2.10 ± 1.54

D0.035cc

0.20 ± 0.38

–0.32 ± 2.34

–0.09 ± 2.22

0.43 ± 0.29

2.80 ± 1.90

3.29 ± 2.21

Brainstem

D1cc

–0.10 ± 0.73

–2.83 ± 4.55

–2.96 ± 4.64

–0.42 ± 0.66

–0.15 ± 3.37

–0.81 ± 3.75

D0.035cc

–0.25 ± 0.83

–3.21 ± 3.22

–3.53 ± 2.76

–0.71 ± 0.58

–1.68 ± 3.51

–2.51 ± 3.58

L Parotid

Dmean

1.13 ± 0.79

4.44 ± 8.13

5.48 ± 8.65

–0.34 ± 2.88

6.49 ± 3.54

5.99 ± 3.28

D50%

1.95 ± 2.13

5.50 ± 18.48

7.25 ± 19.63

–3.61 ± 5.13

15.68 ± 10.07

13.03 ± 12.33

R Parotid

Dmean

–0.05 ± 1.13

1.88 ± 11.87

1.78 ± 12.78

3.44 ± 2.20

–1.23 ± 2.17

1.59 ± 4.71

D50%

–0.10 ± 2.47

–0.60 ± 14.95

0.49 ± 16.12

4.69 ± 6.14

–1.97 ± 5.55

5.17 ± 10.57

Larynx

Dmean

–0.12 ± 0.14

–0.61 ± 2.46

–0.69 ± 2.56

0.45 ± 0.60

–0.11 ± 1.82

0.09 ± 1.24

D50%

–0.21 ± 0.25

–0.84 ± 2.34

–0.98 ± 2.50

0.18 ± 0.46

–0.12 ± 1.68

0.17 ± 1.45

Mandible

D1cc

0.27 ± 0.40

0.64 ± 0.49

0.90 ± 0.79

–0.73 ± 1.56

1.44 ± 1.85

0.52 ± 0.34

D0.035cc

0.45 ± 0.40

0.83 ± 0.38

1.23 ± 0.58

0.65 ± 0.52

1.41 ± 1.42

1.65 ± 1.21

Table 5. The overall mean percentage dose variation in targets and organs at risk (OARs) for 10 intensity-modulated radiation therapy (IMRT) and 10 volumetric modulated arc therapy (VMAT) patients for corresponding dose metrics with moderate setup error correction approach

ROI

Dose-Index

IMRT (n = 10)

VMAT (n = 10)

ΔDR (%)

Mean ± SD

ΔDT (%)

Mean ± SD

ΔDT+R (%)

Mean ± SD

ΔDR (%)

Mean ± SD

ΔDT (%)

Mean ± SD

ΔDT+R (%)

Mean ± SD

CTV-60

D98%

–0.3 ± 0.1

–0.3 ± 0.3

–0.5 ± 0.4

–0.1 ± 0.1

–0.3 ± 0.2

–0. 4 ± 0.3

D95%

–0.1 ± 0.1

–0.2 ± 0.2

–0.3 ± 0.3

0.0 ± 0.1

–0.3 ± 0.1

–0.3 ± 0.2

D2%

0.1 ± 0.1

0. 3 ± 0.3

0.4 ± 0.3

0.1 ± 0.1

0.1 ± 0.2

0.2 ± 0.1

D0.035cc

0.4 ± 0.5

0.5 ± 0.4

0.8 ± 0.7

0.5 ± 0.7

0.6 ± 0.4

1.3 ± 1.3

CTV-54

D98%

0.0 ± 0.1

–0.6 ± 0.6

–0.6 ± 0.6

–0.3 ± 0.4

0.1 ± 0. 2

–0.2 ± 0.3

D95%

0.0 ± 0.0

–0.4 ± 0.4

–0.4 ± 0.4

–0.3 ± 0.4

0.1 ± 0.2

–0.2 ± 0.4

D2%

0.2 ± 0.2

0.6 ± 0.4

0.8 ± 0.5

0.4 ± 0.5

0.4 ± 0.6

0.8 ± 0.4

D0.035cc

0.2 ± 0.2

1.0 ± 0.4

1.3 ± 0.6

0.8 ± 1.1

0.6 ± 0.8

1.4 ± 0.4

PTV-60

D98%

–0.5 ± 0.4

–3.3 ± 2.7

–3.7 ± 2.9

–0.4 ± 0.3

–2.7 ± 1.1

–3.1 ± 1.2

D95%

–0.3 ± 0.3

–2.1 ± 1.9

–2.3 ± 2.1

–0.2 ± 0.2

–1.6 ± 0.8

–1.8 ± 0.8

D2%

0.1 ± 0.1

0.4 ± 0.3

0.5 ± 0.3

0.2 ± 0.1

0.0 ± 0.0

0.2 ± 0.1

D0.035cc

0.6 ± 0.6

0.9 ± 1.1

1.3 ± 1.1

0.7 ± 0.7

1.3 ± 0.7

2.1 ± 1.2

PTV-54

D98%

–0.4 ± 0.2

–4.5 ± 3.0

–5.0 ± 3.0

–0.5 ± 0.5

–2.4 ± 1.3

–3.0 ± 1.5

D95%

–0.2 ± 0.1

–2.5 ± 2.0

–2.7 ± 2.1

–0.3 ± 0.4

–1.0 ± 0.5

–1.3 ± 0.8

D2%

0.2 ± 0.1

0.6 ± 0.4

0.8 ± 0.4

0.5 ± 0.5

0.5 ± 0.6

0.9 ± 0.2

D0.035cc

0.4 ± 0.4

1.6 ± 1.3

1.9 ± 1.3

1. 0 ± 1.3

0.8 ± 1.7

1.7 ± 0.9

Spinalcord

D1cc

–0.1 ± 0.3

–0.1 ± 1.8

–0.2 ± 1.9

1.0 ± 1.4

0.6 ± 2.4

1.6 ± 1.5

D0.035cc

0.1 ± 0.3

–0.2 ± 2.0

–0.1 ± 1.9

0.3 ± 0.3

2.4 ± 1.8

2.7 ± 2.1

Brainstem

D1cc

0.1 ± 0.5

–1.8 ± 3.5

–1.7 ± 3.6

–0.5 ± 0.5

–0.2 ± 2.5

–0.7 ± 3.0

D0.035cc

–0.1 ± 0.7

–2.6 ± 2.3

–2.7 ± 1.9

–0.7 ± 0.3

–1.3 ± 2.7

–2.1 ± 2.9

L Parotid

Dmean

0.9 ± 0.8

3.4 ± 6.2

4.3 ± 6.6

–0.1 ± 2.4

5.3 ± 2.4

5.2 ± 3.2

D50%

1.6 ± 2.0

3.7 ± 13.6

5.7 ± 15.0

–2.0 ± 4.1

11.2 ± 6.7

9.8 ± 8.9

R Parotid

Dmean

–0.1 ± 0.8

1.3 ± 9.5

1.2 ± 10.1

2.3 ± 2.1

–1.6 ± 2.0

0.7 ± 4.2

D50%

–0.2 ± 1.9

–0.7 ± 10.4

–1.3 ± 11.2

5.8 ± 5.5

0.2 ± 4.9

6.0 ± 10.0

Larynx

Dmean

–0.1 ± 0.1

–0.5 ± 1.9

–0.6 ± 2.0

0.2 ± 0.6

–0.4 ± 1.4

–0.2 ± 0.8

D50%

–0.2 ± 0.2

–0.7 ± 1.8

–0. 8 ± 1.9

0.3 ± 0.3

–0.1 ± 1.4

0.2 ± 1.1

Mandible

D1cc

0.2 ± 0.3

0.4 ± 0.6

0.5 ± 0.9

–1.0 ± 1.5

1.0 ± 1.9

0.1 ± 0.6

D0.035cc

0.3 ± 0.3

0.5 ± 0.5

0.8 ± 0.8

0.1 ± 0.2

0.6 ± 1.0

0.8 ± 1.0

Discussion

Interfractional setup errors in ca-tongue are mainly attributed to changes in the patient’s position, shape, or size due to weight loss and displacement of the target relative to the skin marks. Geometrical deviations are classified into systematic errors (treatment preparations) and random errors (treatment execution). Systematic error leads to a displacement of the dose distribution, and random error leads to the blurring of the dose distribution with respect to the CTV [43]. Ideally, treatment setup errors cannot be separated into the RError and TError. However, RError and TError alone were analyzed to evaluate how uncorrected RError affects the doses to targets and OARs where 6-DoF couch is not onboard and how uncorrected TError affects the doses to targets and OARs independently to compare with the previous dosimetric studies that evaluated the dosimetric impact of translational errors on pCT, which did not account for the internal organ geometric variation during the treatment.

The overall population mean error (Mpop), systematic error (), and random error (σ) were within 1.2–1.6 mm and 0.1–0.7 degrees. This indicates that the overall average tongue dislocation was smaller. The lateral, longitudinal, and vertical translational axes had CTV to PTV margins of 4.7 mm, 3.9 mm, and 4.5 mm, respectively, which were consistent with earlier studies for the PTV margin in head and neck cancer [13, 18–20]. However, Mesias et al. found a larger PTV margin of 4.9 mm, 6.4 mm, and 5.8 mm in the lateral, longitudinal, and vertical axes, respectively [21].

Figure 2 illustrates the dosimetric impact of uncorrected RError on the CBCT of patient 1 for a single fraction. Figures 2A and 2B illustrate the original plan dose distribution on pCT. The dose deviation at the periphery of target and OAR volumes due to RError is clearly visible in Figures 2CD. Figures 3A–C illustrate the DVH comparison for a single fraction of patient 1 for RError, TError, and T+RError, respectively, with the reference plan (Ref). The dose deviation in CTVs, PTVs, and OARs is higher in TError, and T+RError compared to RError. This is attributed to the larger displacement of treatment volume in TError, and T+RError with translation error coupled with rotational error. RError alone generally causes dose variation at the edges or periphery of the target and OAR volumes (Fig. 2CD).

The box and whisker plot in Figures 4 and 5 depict the overall dosimetric impact for the evaluated dose metric in all 20 patients for CTVs, PTVs, and OARs. The outliers depict the maximum deviation in the evaluated dose metrics for CTVs, PTVs, and OARs. This is attributed to the large setup variations in some patients.

The dosimetric impact of uncorrected RError, TError, and T+RError for all treatment fractions and for moderate correction of RError, TError, and T+RError in the first three fractions and weekly thereafter (Tab. 1) showed a similar nature in targets and OARs. However, the magnitude of percentage dose deviation ΔDR (%), ΔDT (%), and ΔDT+R (%) for RError, TError, and T+RError, respectively, were slightly lower with moderate setup error correction compared to no setup error correction for all fractions.

The absolute magnitude of mean ΔD (%) in target volumes for D98%, D95%, D2%, and D0.035cc increased with RError, TError, and T+RError (Fig. 4). This can be attributed to the increasing deviation in the congruence between target volume and planned treatment volume with RError, TError, and T+RError, respectively. The mean absolute dose (Gy) for D98% and D95% was reduced but increased for D2% and D0.035cc in target volumes with RError, TError, and T+RError and was statistically significant (p < 0.05) (Tab. 2, 3). This can be attributed to the increasing deviation of target volume from planned treatment volume. This results in underdosing of target volume and increasing the high dose volume within the target volume due to highly conformal dose of IMRT and VMAT plans. Kaur et al. [29] also reported similar results for uncorrected TError with a significant p-value in head and neck cancer. Our results for RError concur with Fu et al. [28] who reported a similar result for D98% in CTV and D95% in PTV for RError. Jiang et al. [30] reported similar results for D98% and D95% in PTV for T+RError.

The mean absolute dose (Gy) variations ΔDR, ΔDT, and ΔDT+R in Spinalcord for D0.035cc were 0.12 ± 0.13 Gy, 0.48 ± 0.96 Gy, and 0.62 ± 1.03 Gy, respectively, with no setup error correction. This can be attributed to the increasing deviation in congruence between the target volume and the planned treatment volume with RError, TError, and T+RError, respectively. Kaur et al. [29] also reported similar results for an uncorrected TError. However, for RError, Fu et al. [28] reported a higher value of 1.2 ± 1.76 Gy for D1cc than our finding of 0.53 ± 1.38 Gy. Similarly, Jiang et al. [30] found a higher value of 1.85 ± 1.26 Gy for D1cc in cervical spine tumors in head and neck cancer when the spine was within the tumor volume. The maximum mean absolute dose (Gy) variation of D0.035cc in the spinal cord, brainstem, and mandible was 0.62 ± 1.03 Gy, –0.97 ± 1.09 Gy, and 0.90 ± 0.59 Gy in ΔDT+R in 20 patients. The maximum mean absolute dose variation of Dmean in the Left Parotid, Right Parotid, and Larynx was 1.6 ± 1.8 Gy, 0.45 ± 0.68 Gy, and –0.17 ± 0.90 Gy in ΔDT+R, ΔDR, and ΔDT, respectively.

The reduction in DR (Gy), DT (Gy), and DT+R (Gy) with respect to DP (Gy) for D98% and D95% in CTV-60, CTV-54, PTV-60, and PTV-54 was statistically significant (p < 0.05) except for DR (Gy) and DT (Gy) in CTV-54 for uncorrected (Tab. 2) and moderately corrected setup errors (Tab. 3). The increase in DR (Gy), DT (Gy), and DT+R (Gy) with respect to DP (Gy) for D2% and D0.035cc in CTV-60, CTV-54, PTV-60, and PTV-54, was statistically significant (p < 0.05) (Tab. 2, 3).

The mean dosimetric impact of the RError on CTVs, PTVs, and OARs was relatively smaller than the TError and T+RError. It is attributed to the PTV margin of 5 mm. However, a significant mean dosimetric impact occurred due to TError and T+RError. The maximum dose variation for the targets and OARs was observed in the T+RError, as the RError, coupled with the TError, could significantly impact the delivered dose. It implies that a smaller RError coupled with a larger TError could significantly increase the dose variation. Similar results were reported by Guckenberger et al. [24], that the RError is of clinical significance and is independent of the TError. Fu et al. [28] reported a substantial decrease in CTV dose for patients with large systematic RError. Similarly, RError in larger targets could significantly affect the dose delivery and dose variation.

The single fraction maximum TError and RError ranged from 7–8 mm and 2.90–3.00, respectively, which resulted in a significant variation of dose metrics in target volumes and OARs. With no setup error correction, the maximum ΔD (%) for D98% in CTV-60, CTV-54, PTV-60, and PTV-54 was –1.2%, –1.9%, –12.0%, and –12.3%, respectively, in the T+RError. The maximum ΔD (%) for D0.035cc in the spinal cord was 6.5% in the T+RError. The maximum ΔD (%) for Dmean in the left parotid and right parotid was 15.8% and 24.6%, respectively, in the T+RError (Fig. 4). Similarly, with moderate setup error correction, the maximum ΔD (%) for D98% in CTV-60, CTV-54, PTV-60, and PTV-54 was –1.0%, –1.7%, –9.2%, and –9.5%, respectively, in the T+RError. The maximum ΔD (%) for D0.035cc in the spinal cord was 5.4% in the T+RError. The maximum ΔD (%) for Dmean in the left parotid and right parotid was 12.2% and 19.6%, respectively, in the T+RError (Fig. 5). This study with no setup error correction and moderate setup error correction approaches demonstrated that for patients with substantial setup errors, the uncorrected 6D setup errors have a potential dosimetric impact on the D98% of CTV-60 and CTV-54. However, the mean dosimetric impact for the study patient cohort was not dosimetrically significant. It is attributed to the uniform PTV margin of 5 mm in the original treatment plan compared to the PTV margins of 4.7 mm, 3.9 mm, and 4.5 mm along the lateral, longitudinal, and vertical axes evaluated for the study patient cohort. For patients with significant setup errors, the uncorrected 6D setup errors have a potential dosimetric impact on the D98% and D95% in PTV-60 and PTV-54. The left parotid showed a significant dosimetric impact on Dmean in TError and RError. For patients with large setup errors, the uncorrected 6D setup errors have a potential dosimetric impact on the D0.035cc of spinal cord and mandible and the Dmean of the left parotid and right parotid. Our study with no setup error correction and moderate setup error correction showed that the uncorrected 6D setup errors result in a significant decrease in the target doses and a non-significant increase in the doses to OARs. It might result in inferior tumor control and increased normal tissue toxicity.

The dosimetric impact of RError, TError, and T+RError for IMRT (10) and VMAT (10) plans on targets and OARs in ca-tongue patients was evaluated with no correction (Tab. 4) and moderate correction of setup error (Tab. 5). For CTV-60, the dose variation in D98% and D95% due to TError, and T+RError in VMAT plans was slightly higher than that in IMRT plans. The dose variation in D98% and D95% for IMRT plans was slightly higher than that in VMAT plans for RError (Tab. 4, 5). However, for PTV-60, the dose variation in D98% and D95% due to RError, TError, and T+RError in IMRT was higher than in VMAT plans (Tab. 4 and 5). For the Spinalcord the dose variation in D1cc and D0.035cc due to RError, TError, and T+RError was higher in VMAT than IMRT plans (Tab. 4, 5). There is no clinically significant difference (> 2%) in dose variation between IMRT and VMAT plans for all targets and OARs except for PTV-54 in D98% due to TError and T+RError, for Spinalcord in D0.035cc due to TError and T+RError, for Braistem in D1cc due to TError and T+RError, for the left parotid in D50% due to TError and T+RError, and for right parotid in Dmean and D50% due to RError and in D50% due to T+RError. This could be due to the comparison of IMRT and VMAT plans for different patients optimized with different priorities for objectives and constraints, and different geometries of targets and OARs. VMAT and IMRT plans could generate similar dose conformity and lower MU with shorter treatment time is the significant advantage of VMAT over IMRT [44–47]. The true comparison of the dosimetric impact of setup error on IMRT and VMAT plans can be evaluated for IMRT and VMAT plans of the same patients.

The limitation of this study was not considering the dosimetric impact of intrafraction error, which has a considerable impact on delivered doses. However, the magnitude of the dosimetric impact of intrafraction setup errors could be smaller than that of interfraction setup errors. Also, the sole aim of this study was to evaluate the dosimetric impact of 6D interfractional setup errors. The dosimetric evaluation was done on CBCT, which could be affected by a larger patient scatter in CBCT compared to pCT. However, this effect was eliminated by generating the CBCT_REF without RError and TError. For dosimetric evaluation, the dose delivered in each fraction was reconstructed on CBCT_REF and compared with the reconstructed doses of RError, TError, and T+RError on pre-treatment CBCT. The absolute dose variation of the setup error was derived from the original treatment plan by applying the percentage dose variation correction obtained from CBCT plans. It is analogous to the method used by Hatton et al. [36]. The limited FOV and scan length of the CBCT restrict this method to the dosimetric evaluation of small tumor volumes in head and neck patients.

Conclusions

This study demonstrated and assessed the dosimetric impact of uncorrected daily rotational, translational, and 6D translational plus rotational setup errors with no setup error correction and moderate setup error correction approaches, indicating that statistically significant underdosing of target volumes (p < 0.05) and significant overdosing of OARs can occur. The substantial magnitude of the maximum dose variation ΔD (%) in PTVs and OARs emphasizes the necessity of accurate daily patient setup verification and target localization with daily correction of interfractional 6D setup errors in modern IMRT and VMAT radiation therapy techniques.

Acknowledgements

Nothing to disclose.

Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article

Funding

Nothing to disclose.

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