Dosimetric Impact of Online Correction via Cone-Beam CT-Based Image Guidance for Stereotactic Lung Radiotherapy

doi:10.1016/j.ijrobp.2010.02.012

International Journal of Radiation OncologyBiologyPhysics

Volume 78, Issue 5, 1 December 2010, Pages 1571-1578

https://doi.org/10.1016/j.ijrobp.2010.02.012 Get rights and content

Purpose

To evaluate the dosimetric impact of online cone-beam computed tomography (CBCT) guided correction in lung stereotactic body radiation therapy (SBRT).

Methods and Materials

Twenty planning and 162 CBCT images from 20 patients undergoing lung SBRT were analyzed. The precorrection CBCT (CBCT after patient setup, no couch correction) was registered to planning CT using soft tissue; couch shift was applied, with a second CBCT for verification (postcorrection CBCT). Targets and normal structures were delineated on CBCTs: gross tumor volume (GTV), clinical target volume (CTV), cord, esophagus, lung, proximal bronchial tree, and aorta. Dose distributions on all organs manifested on each CBCT were compared with those planned on the CT.

Results

Without CBCT guided target position correction, target dose reduced with respect to treatment plan. Mean and standard deviation of treatment dose discrepancy from the plan were −3.2% (4.9%), −2.1% (4.4%), −6.1% (10.7%), and −3.5% (7%) for GTV D_99%, GTV D_95%, CTV D_99%, and CTV D_95%, respectively. With CBCT correction, the results were −0.4% (2.6%), 0.1% (1.7%), −0.3% (4.2%), and 0.5% (3%). Mean and standard deviation of the difference in normal organ maximum dose were 2.2% (6.5%) before correction and 2.4% (5.9%) after correction for esophagus; 6.1% (14.1%) and 3.8% (8.1%) for cord; 3.1% (17.5%) and 6.2% (9.8%) for proximal bronchial tree; and 17.7% (19.5%) and 14.1% (17%) for aorta.

Conclusion

Online CBCT guidance improves the accuracy of target dose delivery for lung SBRT. However, treatment dose to normal tissue can vary regardless of the correction. Normal tissues should be considered during target registration, according to target proximity.

Introduction

Stereotactic body radiation therapy (SBRT) involves high-dose radiation delivery in 1 to 5 fractions (1). To achieve a high biologically effective dose to tumor while sparing adjacent normal tissue, precision in delivery and patient setup is required. The improved local control achieved with SBRT is appealing for the frail population of medically inoperable Stage I non–small-cell lung cancer (NSCLC) patients who have difficulty coming for 6 to 8 weeks of therapy 2, 3, 4. Lagerwaard et al.(5) and many other groups have recently reported excellent local control and minimal toxicity in medically inoperable Stage I NSCLC, suggesting that SBRT may be the new treatment of choice 6, 7, 8.

Although these early results are very promising, improvements in delivery, target dosimetric coverage, and patient positioning are warranted to possibly further lower toxicity, improve local control, or maybe even deescalate dose. As hypofractionation is applied to targets that are closer to sensitive structures (e.g., central tumors close to the esophagus and trachea) reducing positional uncertainties will become even more important. Volumetric image-guided radiation therapy (IGRT), such as daily online cone-beam computed tomography (CBCT), allows exquisite visualization of tumor and normal tissues before, during, and after each fraction. Advances in clinical feasibility of volumetric IGRT are crucial for SBRT because setup accuracy and precision are essential for implementation 9, 10, 11, 12, 13. Target position variations 14, 15, 16 strongly affect the cumulative dose delivered to targets and can translate into a need for large margins or reduced tumor control. Critical adjacent structures may also move independently of the target, affecting the delivered dose, and translating into unexpected treatment-related morbidities or inaccurate dose response.

Understanding geometric variation of targets and organs at risk (OARs) is crucial in this setting because of the sharp dose gradient and high dose per fraction. In this article, we present a comprehensive study of the dosimetric impact of anatomic position uncertainty with and without daily online CBCT-mediated correction in patients treated with lung SBRT. A dosimetric analysis of the behavior of targets and OAR was assessed, and the differences between planned and delivered target and OAR doses were quantified.

Section snippets

Patient eligibility

Patients with medically inoperable Stage I NSCLC or solitary lung metastasis treated with hypofractionated IGRT as part of an institutional review board—approved Phase II clinical trial were analyzed. All underwent a pretreatment staging evaluation that included a history, imaging, physical examination, and histologic documentation of malignancy. Patient and tumor characteristics are listed in Table 1.

Simulation

Patients were immobilized in a stereotactic body frame (SBF) (Elekta, Crawley, UK) (n = 15) or

Results

Twenty patients were treated with lung SBRT between November 2005 and December 2006. Twenty free-breathing planning CT scans and 162 CBCT scans (85 precorrection scans and 77 postcorrection scans) were acquired during the total 85 treatment fractions. Eight of 85 treatments had initial treatment position errors on precorrection CBCT of less than 2 mm, and therefore no couch correction was necessary. All other treatments required couch corrections and therefore were submitted to postcorrection

Discussion

This study evaluated the dosimetric impact of daily online correction via CBCT for lung SBRT using data acquired from CBCT before and after volumetric positional correction. Because of the sharp dose gradient and fractionation schedule typical of lung SBRT, differences between planned vs. reconstructed (delivered) target doses were significant. Daily CBCT-guided correction was applied for 91% of the total treatment fractions with target displacements greater than 2 mm in at least one direction.

Conclusions

In this study, we evaluated the dosimetric impact of using daily online CBCT for patients treated with lung SBRT. Delivered doses to target volumes and OARs were evaluated and demonstrated the importance of daily online target position correction after initial setup using stereotactic coordinates or skin tattoos. The differences between planned vs. recalculated (delivered) doses were significant, with potentially inferior clinical outcomes in the absence of volumetric image guidance. The

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Cited by (23)

Delivered dose–effect analysis of radiation induced rib fractures after thoracic SBRT
2021, Radiotherapy and Oncology
Anatomical changes during the stereotactic body radiation therapy (SBRT) of early stage non-small cell lung cancer (NSCLC) may cause the delivered dose to deviate from the planned dose. We investigate if normal tissue complication probability (NTCP) models based on the delivered dose predict radiation-induced rib fractures better than models based on the planned dose.
437 NSCLC patients treated to a median dose of 3x18 Gy were included. Delivered dose was estimated by accumulating EQD2-corrected fraction doses after being deformed with daily CBCT-to-planning CT deformable image registration.
Dosimetric parameters $D_{x}$ (dose to a relative volume x) were extracted for each rib included in the CBCTs field-of-view. An NTCP model was constructed for both planned and delivered dose, optimizing the parameters TD₅₀ (dose with 50% toxicity risk), m (steepness of the curve) and x, using maximum likelihood estimation. Best NTCP model was determined using Akaike weights (Aw). Differences between the models were tested for significance using the Vuong’s test.
Median time to fracture of 110 fractured ribs was 22.5 months. The maximum rib dose, $D_{0}$ , best predicted fractures for both planned and delivered dose. The average delivered $D_{0}$ was significantly lower than planned (p < 0.001). NTCP model based on the delivered $D_{0}$ was the best, with Aw = 0.95. The models were not significantly different.
Delivered maximum dose to the ribs was significantly lower than planned. The NTCP model based on delivered dose improved predictions of radiation-induced rib fractures but did not reach statistical significance.
European Organization for Research and Treatment of Cancer (EORTC) recommendations for planning and delivery of high-dose, high precision radiotherapy for lung cancer
2017, Radiotherapy and Oncology
To update literature-based recommendations for techniques used in high-precision thoracic radiotherapy for lung cancer, in both routine practice and clinical trials.
A literature search was performed to identify published articles that were considered clinically relevant and practical to use. Recommendations were categorised under the following headings: patient positioning and immobilisation, Tumour and nodal changes, CT and FDG-PET imaging, target volumes definition, radiotherapy treatment planning and treatment delivery. An adapted grading of evidence from the Infectious Disease Society of America, and for models the TRIPOD criteria, were used.
Recommendations were identified for each of the above categories.
Recommendations for the clinical implementation of high-precision conformal radiotherapy and stereotactic body radiotherapy for lung tumours were identified from the literature. Techniques that were considered investigational at present are highlighted.
A comparison between radiation therapists and medical specialists in the use of kilovoltage cone-beam computed tomography scans for potential lung cancer radiotherapy target verification and adaptation
2016, Medical Dosimetry
Citation Excerpt :
The study also demonstrated that tumor localization provides improved target coverage and decreased dose to critical structures. A study by Galerani et al.4 investigating the dosimetric effect of online kVCBCT soft tissue image guidance for lung cancer radiotherapy concluded that soft tissue correction improves the accuracy of treatment delivery. This study demonstrated that without soft tissue verification using cone-beam computed tomography (CBCT), the overall target dose coverage would be reduced on the treatment plan.
Target volume matching using cone-beam computed tomography (CBCT) is the preferred treatment verification method for lung cancer in many centers. However, radiation therapists (RTs) are trained in bony matching and not soft tissue matching. The purpose of this study was to determine whether RTs were equivalent to radiation oncologists (ROs) and radiologists (RDs) in alignment of the treatment CBCT with the gross tumor volume (GTV) defined at planning and in delineating the GTV on the treatment CBCT, as may be necessary for adaptive radiotherapy. In this study, 10 RTs, 1 RO, and 1 RD performed a manual tumor alignment and correction of the planning GTV to a treatment CBCT to generate an isocenter correction distance for 15 patient data sets. Participants also contoured the GTV on the same data sets. The isocenter correction distance and the contoured GTVs from the RTs were compared with the RD and RO. The mean difference in isocenter correction distances was 0.40 cm between the RO and RD, 0.51 cm between the RTs, and RO and 0.42 cm between the RTs and RD. The 95% CIs were smaller than the equivalence limit of 0.5 cm, indicating that the RTs were equivalent to the RO and RD. For GTV delineation comparisons, the RTs were not found to be equivalent to the RD or RO. The alignment of the planning defined GTV and treatment CBCT using soft tissue matching by the RTs has been shown to be equivalent to those by the RO and RD. However, tumor delineation by the RTs on the treatment CBCT was not equivalent to that of the RO and RD. Thus, it may be appropriate for RTs to undertake soft tissue alignment based on CBCT; however, further investigation may be necessary before RTs undertake delineation for adaptive radiotherapy purposes.
Toxicity after central versus peripheral lung stereotactic body radiation therapy: A propensity score matched-pair analysis
2015, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
One patient with a peripheral lesion treated with 12 Gy × 5 and prolonged adjuvant chemotherapy developed a chronic fungal infection with empyema (grade 3) and pleural fistula (grade 3) 19 months after treatment. One patient treated early in the clinical trial (March 2006) with a central lesion close to the aorta before institution of a great vessel constraint had an aortic dissection (grade 4 vascular toxicity) 1 month after SBRT (12 Gy × 4) as previously discussed (15); she is currently alive without disease 7.7 years from treatment. A patient with a peripheral tumor meeting all lung DVH constraints had grade 4 DLCO decline at 6 week PFT.
To compare toxicity after stereotactic body radiation therapy (SBRT) for “central” tumors—within 2 cm of the proximal bronchial tree or with planning tumor volume (PTV) touching mediastinum—versus noncentral (“peripheral”) lung tumors.
From November 2005 to January 2011, 229 tumors (110 central, 119 peripheral; T1-3N0M0 non–small-cell lung cancer and limited lung metastases) in 196 consecutive patients followed prospectively at a single institution received moderate-dose SBRT (48-60 Gy in 4-5 fractions [biologic effective dose=100-132 Gy, α/β=10]) using 4-dimensional planning, online image-guided radiation therapy, and institutional dose constraints. Clinical adverse events (AEs) were graded prospectively at clinical and radiographic follow-up using Common Terminology Criteria for Adverse Events version 3.0. Pulmonary function test (PFT) decline was graded as 2 (25%-49.9% decline), 3 (50.0%-74.9% decline), or 4 (≥75.0% decline). Central/peripheral location was assessed retrospectively on planning CT scans. Groups were compared after propensity score matching. Characteristics were compared with χ² and 2-tailed t tests, adverse events with χ² test-for-trend, and cumulative incidence using competing risks analysis (Gray's test).
With 79 central and 79 peripheral tumors matched, no differences in AEs were observed after 17 months median follow-up. Two-year cumulative incidences of grade ≥2 pain, musculoskeletal, pulmonary, and skin AEs were 14%, 5%, 6%, and 10% (central) versus 19%, 10%, 10%, and 3% (peripheral), respectively (P=.31, .38, .70, and .09). Grade ≥2 cardiovascular, gastrointestinal, and central nervous system AEs were rare (<1%). Two-year incidences of grade ≥2 clinical AEs (28% vs 25%, P=.79), grade ≥2 PFT decline (36% vs 34%, P=.94), grade ≥3 clinical AEs (3% vs 7%, P=.48), and grade ≥3 PFT decline (0 vs 10%, P=.11) were similar for central versus peripheral tumors, respectively. Pooled 2-year incidences of grades 4 and 5 AEs were <1% and 0%, respectively, in both the prematched and matched groups.
Moderate-dose SBRT with these techniques yields a similarly safe toxicity profile for both central and peripheral lung tumors.
Dose-response relationship with clinical outcome for lung stereotactic body radiotherapy (SBRT) delivered via online image guidance
2014, Radiotherapy and Oncology
Citation Excerpt :
In a study at Indiana University, 37 patients underwent dose escalation from 8 Gy × 3 fractions (BED10 = 43.2 Gy) to 20 Gy × 3 fractions (BED10 = 180 Gy) to the 80% isodose line based on homogeneous dose calculation without encountering predefined dose-limiting toxicities [9]. Seventy patients were subsequently treated with 20–22 Gy × 3 fractions to the 80% isodose line and demonstrated a 3-year local control rate of 88% [10,11]. This 20 Gy × 3 regimen was subsequently administered in RTOG 0236 where the 3-year local control rate was 98% in 55 patients [12].
To examine potential dose–response relationships with various non-small-cell lung cancer (NSCLC) SBRT fractionation regimens delivered with online CT-based image guidance.
505 tumors in 483 patients with clinical stage T1-T2N0 NSCLC were treated with SBRT using on-line cone-beam-CT-based image guidance at 5 institutions (1998–2010). Median maximum tumor dimension was 2.6 cm (range 0.9–8.5 cm). Dose fractionation prescription was according to each institution’s protocol with the most common schedules of 18–20 GyX3, 12 GyX4, 12 GyX5, 12.5 GyX3, 7.5 GyX8 (median = 54 Gy, 3 fractions). Median prescription (Rx) BED₁₀ = 132 Gy (50.4–180). Median values (Gy) of 3D planned doses for BED₁₀ were GTV_min = 164.1, GTV_mean = 188.4, GTV_max = 205.9, PTV_min = 113.9, PTV D99 = 123.9, PTV_mean = 164.7, PTV D1 = 197.3, PTV_max = 210.7. Mean follow-up = 1.6 years.
26 cases (5%) had local recurrence (LR) for a 2-year rate of 6% and 3-year rate of 9%. All BED₁₀ GTV&PTV endpoints were associated with LR as continuous variables on univariate analysis (p < 0.05). Rx and PTV_mean dose appeared to have the highest correlation with LR with area under ROC curve of 0.69 and 0.65 respectively and optimal cut points of 105 and 125 Gy, respectively. 2-year LR was 4% for PTV_mean > 125 vs 17% for <125 Gy (p < 0.01) with sensitivity = 84% and specificity = 57% for predicting LR. 2-year LR for Rx BED₁₀ > 105 was 4% vs 15% for <105 Gy (p < 0.01). Longer treatment duration (⩾11 elapsed days) demonstrated a 2-year LR of 14% vs 4% for ⩽10 days (p < 0.01). GTV size was associated with LR on univariate analysis as a continuous variable (p = 0.02) with 2-year LR = 3% for <2.7 cm vs 9% for ⩾2.7 cm (p = 0.03). BED₁₀ (p = 0.01) and elapsed days during RT (p = 0.05) were independent predictors on multivariate analysis as continuous variables.
There is a substantial dose–response relationship for local control of NSCLC following image-guided SBRT with optimal PTV_mean BED₁₀ > 125 Gy. Shorter treatment duration was also associated with better local control in this dataset.
Dose-guided radiotherapy: Potential benefit of online dose recalculation for stereotactic lung irradiation in patients with non-small-cell lung cancer
2012, International Journal of Radiation Oncology Biology Physics
To determine whether dose-guided radiotherapy (i.e., online recalculation and evaluation of the actual dose distribution) can improve decision making for lung cancer patients treated with stereotactic body radiotherapy.
For this study 108 cone-beam computed tomography (CBCT) scans of 10 non-small-cell lung cancer patients treated with stereotactic body radiotherapy were analyzed retrospectively. The treatment plans were recalculated on the CBCT scans. The V_100% of the internal target volume (ITV) and D_max of the organs at risk (OARs) were analyzed. Results from the recalculated data were compared with dose estimates for target and OARs by superposition of the originally planned dose distribution on CBCT geometry (i.e., the original dose distribution was assumed to be spatially invariant).
Before position correction was applied the V_100% of the ITV was 100% in 65% of the cases when an ITV–PTV margin of 5 mm was used and 52% of the cases when a margin of 3 mm was used. After position correction, the difference of D_max in the OARs with respect to the treatment plan was within 5% in the majority of the cases. When the dose was not recalculated but estimated assuming an invariant dose distribution, clinically relevant errors occurred in both the ITV and the OARs.
Dose-guided radiotherapy can be used to determine the actual dose in OARs when the target has moved with respect to the OARs. When the workflow is optimized for speed, it can be used to prevent unnecessary position corrections. Estimating the dose by assuming an invariant dose instead of recalculation of the dose gives clinically relevant errors.

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Physics ContributionDosimetric Impact of Online Correction via Cone-Beam CT-Based Image Guidance for Stereotactic Lung Radiotherapy

Purpose

Methods and Materials

Results

Conclusion

Introduction

Section snippets

Patient eligibility

Simulation

Results

Discussion

Conclusions

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Chest

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Physics Contribution
Dosimetric Impact of Online Correction via Cone-Beam CT-Based Image Guidance for Stereotactic Lung Radiotherapy