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J. Belderbos
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MO17 - Radiotherapy I: Stereotactic Ablative Body Radiotherapy (ID 106)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 1
- Moderators:M. Zwitter, S.K. Vinod
- Coordinates: 10/29/2013, 16:15 - 17:45, Bayside 204 A+B, Level 2
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MO17.08 - TCP modeling in Stereotactic Body Radiotherapy for early stage non small cell lung cancer: is a dose-volume effect present? (ID 2205)
17:00 - 17:05 | Author(s): J. Belderbos
- Abstract
- Presentation
Background
In early stage non-small cell lung cancer (NSCLC) stereotactic body radiotherapy (SBRT) has become standard of care for inoperable patients. Tumor size >3cm was reported to be a predictor of local recurrence (LR), suggesting a dose-volume effect. Recently, the dose effect relation was questioned[1]. We used a Tumor-Control-Probability (TCP) model on a large pooled multi-center cohort to test this.Methods
850 patients were analyzed from our five institutes. Patients received a 4D CT-scan and plans were inversely optimized using advanced dose calculation algorithms. Treatment was delivered using online cone-beam CT guidance. Immobilization, margins, dose prescription and treatment planning was performed according to institute specific protocols. Median tumor diameter was 2.2 cm (range:0.7-8.0), median prescribed dose was 54 Gy (range:18-64) and median number of fractions were 3 (range:1-10). LRs were either biopsy proven or defined as a FDG-PET positive growing mass on CT-scan. The Web-Nahum TCP-model[2] was fitted to LR-data using maximum-likelihood estimation by optimizing its parameters: α representing the population-average radio-sensitivity, σ~α~ representing the population-variation in α and ρ the clonogen density. Input variables were the patient specific Gross Tumor Volume (estimated from the tumor diameter), for the dosimetric parameter PTV-D~min~, D~max~, D~mean~, D~1~, D~99~ were evaluated after conversion to Biological-Effective-Dose (BED) using the LQ-model with α/β=10Gy. We tested the optimized TCP model against a random model in which TCP was fixed independent of dose and volume. The optimal model was selected based on the Akaike-Information-Criterion (AIC).Results
After a median follow up (FU) of 17 months (range:0-93), 43 LRs (5%) were diagnosed at 14 months FU (range:2-56), of which 25 tumors were biopsy proven and 18 recurrences diagnosed on PET-CT. The PTV-BED~mean~ based TCP model showed the best fit with parameters α=0.43Gy[-1] (CI:0.33–0.75) and σ~α~=0.17 Gy[-1] (CI:0.11–0.37). The model-fit was insensitive to ρ and set to literature values: 10[7]/cm[3]. The AIC of the optimal model was 12 units higher than the random model indicating a clear dose-volume-effect. At high PTV~mean~-BEDs, however, the volume effect is modest. Additionally, the AIC of the BED corrected model was 9.4 units higher than the BED uncorrected model. Figure 1Conclusion
A dose-volume-effect relation in SBRT for early stage NSCLC for local control was derived in a large cohort of patients. This dose-effect relation requires validation in independent datasets and prospective trials. 1.van Baardwijk,Rad.Onc.,2012. 2.Web&Nahum,PMB,1993.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO23 - Radiotherapy II: Lung Toxicity, Target Definition and Quality Assurance (ID 107)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 2
- Moderators:M.M. Tin, F. Macbeth
- Coordinates: 10/30/2013, 10:30 - 12:00, Bayside 204 A+B, Level 2
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MO23.07 - Impact of a gradient-based FDG-PET auto-contouring method on non-small cell lung cancer delineation (ID 1993)
11:10 - 11:15 | Author(s): J. Belderbos
- Abstract
- Presentation
Background
Manual target volume delineation using CT/FDG-PET is the standard method used for radiotherapy treatment planning of non-small cell lung cancer (NSCLC) patients. Since manual delineation is prone to inter-observer variability and is time consuming, many FDG-PET auto-contouring methods were proposed in literature. The purpose of this study was to investigate to what extent a gradient-based FDG-PET auto-contouring method reduces observer variation, reduces delineation time and influences delineation behavior in radiotherapy treatment planning for NSCLC patients.Methods
Seven radiation oncologists (observers) dedicated to lung cancer treatment delineated the primary tumor (PT) and involved lymph nodes (LN) for 10 patients with stage IIA-IIIB NSCLC on a co-registered CT/FDG-PET scan. The study was separated in two phases. In the first phase, the observers manually delineated the PT and LN for all patients. For the second phase (four months later), auto-contours were generated for both the PT and LN using a gradient-based FDG-PET segmentation method. Bone and air tissue were removed from these auto-contours using CT thresholding. These auto-contours were provided as initial delineation and were adapted by the observers. Delineation times, delineated contours and agreement with the auto-contour were analyzed. Delineated contours were analyzed based on volume, the ratio between the common volume and the encompassing volume (C/E), Dice Index (DI), local standard deviation (SD) and the local distance between median surface and delineated surface. Regions were identified where the observers did or did not change the provided auto-contours.Results
The observers agreed with the provided auto-contour for 37.3% of the PT and for 42.6% of the LN. Notable regions of agreement were the tumor/bone and tumor/air interfaces. The mean delineation time was reduced by 23.9% from 25.5 minutes in phase 1 to 19.4 minutes for phase 2 (p=0.000). The mean delineated volume was smaller in phase 2 compared to phase 1: 8.9% for the PT (155.8 to 142.0 cm[3], p=0.000) and by 9.1% for the LN (13.2 to 12.0 cm[3], p=0.001), respectively. The C/E ratio and DI both did not change significantly and were 0.79 and 0.88 for the PT and 0.54 and 0.67 for the LN in both phases. The mean local SD for the PT was 1.7 mm and 1.5 mm and for the LN was 1.5 mm and 1.4 mm and both did not change significantly, for both phases respectively. The mean distance between the median surface and PT delineations was slightly reduced from 2.1 to 1.8 mm for phase 2, and was 2.0 mm for the LN in both phases.Conclusion
The gradient-based FDG-PET auto-contouring method reduced delineation time by 24%, but was sufficient in only 37.3% of the primary tumors and 42.6% of the involved lymph nodes; most notably at the tumor/bone and tumor/air interfaces segmented using the CT scan. The results suggest the FDG-PET auto-contour is currently primarily used for localization, and not so much for delineation. Multi-modal auto-contouring has the potential to reduce inter-observer variation when further developed in close collaboration with radiation oncologists.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO23.09 - Intra Thoracic Anatomical Changes (ITAC) in lung cancer patients during the course of radiotherapy (ID 2699)
11:20 - 11:25 | Author(s): J. Belderbos
- Abstract
- Presentation
Background
Cone beam-CT (CBCT) guidance is routinely used for setup verification of lung cancer patients treated with radiotherapy. CBCT’s frequently show intra-thoracic anatomical changes (ITAC) during treatment. We developed a protocol as a decision support system to guide the radiation technologist in prioritizing these changes. The purpose of this study was to quantify these ITAC during the radiotherapy course and evaluate the current decision protocol.Methods
The CBCT-scans (made the first 3 fractions and weekly thereafter) of all lung cancer patients treated in 2010 in our institute with radical radiotherapy were evaluated. Each CBCT-scan was visually compared with the planning-CT and all visible ITAC were scored. Additionally, our decision protocol called “traffic-light protocol” was retrospectively applied to all CBCT-scans. The traffic-light protocol has three urgency levels: 1) red: ITAC that likely have a considerable impact on the delivered dose to the primary tumor and/or involved lymph-nodes such as tumor shifts outside the high dose region, large in- or decrease of atelectasis; 2) orange: ITAC with likely moderate impact on the dose distribution such as tumor progression, minor in- or decrease of atelectasis, pleural effusion and post obstructive pneumonia; 3) green: ITAC with likely negligible impact on the dose distribution such as tumor regression without considerable centre of mass displacement or other anatomical changes. For level red changes, the radiation oncologist needs to be consulted immediately before the treatment fraction is delivered. For level orange, the radiation oncologist will be informed by email and a response is required before the next fraction. For level green, the radiation oncologist is informed but no response is required.Results
In total 1500 CBCT-scans of 177 patients were evaluated. All patients received radical radiotherapy (≥50 Gy); 97 patients with concurrent chemoradiation, 23 with sequential chemoradiation and 57 with radiotherapy only. In 128 patients (72%) ITAC were observed with maximum level red, orange and green in 12%, 36% and 24% respectively. Fourteen patients (10%) required a new CT and treatment plan to account for the changed anatomy. Most ITAC occurred in the first week (55%). Of all patients with ITAC during treatment, 45%, 36% and 17% had 1, 2, and ≥3 ITAC respectively. Types of observed ITAC were evident regression (36%), considerable tumor baseline shift (28%), changes in atelectasis (15%), tumor progression (11%), pleural effusion (7%) and pneumonia (3%). Progression seen on the CBCT had a significant correlation with changes in week 1 (p<1e3), and level red changes (p=0.01).Conclusion
ITAC have been observed in 72% of all lung cancer patients during radical radiotherapy. In 12% of the patients the radiation oncologist needed to respond immediately and in 10% of the patients a new planning-CT was made to mitigate the risk of tumor under dosing. Volumetric image guided radiotherapy in combination with a decision protocol is recommended for lung cancer patients treated with radical radiotherapy. In our institute we implemented daily CBCT guidance for accurate patient alignment and simultaneously capture ITAC as soon as possible.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O10 - Stereotactic Ablative Body Radiotherapy (ID 104)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 1
- Moderators:H. Onishi, J.Y. Chang
- Coordinates: 10/28/2013, 16:15 - 17:45, Parkside 110 A+B, Level 1
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O10.07 - Dose-response analysis of radiation induced rib fractures after SBRT for NSCLC (ID 2690)
17:20 - 17:30 | Author(s): J. Belderbos
- Abstract
- Presentation
Background
Symptomatic rib fractures occur in approximately 5% of patients treated with SBRT for early stage NSCLC. Only in small patient cohorts has the dose-effect relation of radiation induced rib fractures been determined. Recent developments in automatic rib segmentation allow determining the dose-effect relation in a large patient cohort, which is the aim of this study.Methods
From 2006-2012 453 patients with early stage NSCLC were treated with SBRT (3x18 Gy). Follow-up (FU) consisted of a physical examination and a CT scan 4 months after treatment and every 6 months up to two years and yearly thereafter. For the first 101 patients with FU>6 months, all ribs were automatically segmented using 15 atlases of manually delineated ribcages. A non-rigid registration followed by a multi-level label fusion produced for each patient a set of ribs. The physical dose distributions were NTD (Normalized Total Dose) corrected with α/β=3 Gy. Cox proportional hazard regression analysis, which takes into account the time to event with patient as random intercept, was used to find the optimal dose parameter. Evaluated were the dose received by x% of the rib D~x~ (x ranged 1-30%) and equivalent uniform dose (EUD) (volume effect 1/n ranged 0.1-60). The Lyman-Kutcher-Burman (LKB) model based on this optimal dose parameter was used to model the dose-effect relationship. Using maximum-likelihood estimation, parameters were median toxic dose (TD~50~), steepness parameter m and 1/n were optimized.Results
In 354 patients with FU>6 months (median 22 months), 38 patients(11%) were diagnosed with a total of 49 rib fractures, symptomatic (grade 2) for 9 patients(2.5%). Included in the dosimetric analysis were 2410 ribs (14 ribs outside field-of-view). 26 ribs in 15 patients(15%) were fractured, symptomatic for 4 patients(4%). In the univariate analysis, all dose parameters significantly correlate with rib fracture (p-values<0.001). Hazard ratios (95%CI) for the parameters with highest log likelihood: D~1~=1.022 (1.017-1.027) and EUD~0.033~=1.021 (1.016-1.026). Multivariate analysis identified EUD as the predictor with the highest log-likelihood and was used in the LKB model. The optimal LKB parameters to predict rib fracture in this dataset were (95% CI): TD~50~=395.5 Gy (244.3-555.1), m=0.348 (0.311-0.384) and 1/n=32.3 (4.82-inf). The risk of rib fracture was <5% in case the NTD-corrected EUD<170 Gy.Figure 1Conclusion
In this subgroup of NSCLC patients treated with 3x18Gy, the risk of rib fracture was significantly correlated to the dose, and was <5% in case the biological dose is kept under 170 Gy.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P2.08 - Poster Session 2 - Radiotherapy (ID 198)
- Event: WCLC 2013
- Type: Poster Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P2.08-020 - Prognositc parameters for local and regional control in locally advanced NSCLC patients treated with concurrent chemo-radiotherapy (ID 2385)
09:30 - 09:30 | Author(s): J. Belderbos
- Abstract
Background
Traditionally, the same radiotherapy dose is prescribed to the primary tumor (PT) and involved lymph nodes (LN) for locally advanced NSCLC patients, independent of volume and metabolic activity of each lesion. On the other hand, the PT and lesions with a high [18]F-FDG uptake are often believed to have a higher recurrence rate. The purpose of this study was therefore to find prognostic parameters for the lesion control probability in locally advanced NSCLC.Methods
A total of 279 patients treated between 2007 and 2011 with 24×2.75Gy IMRT and concurrent daily low dose cisplatin were included in this retrospective analysis. Patients had a staging FDG-PET scan within 6 weeks prior the start of treatment. For follow-up, CT thorax was performed 4-6 weeks after treatment and at 3-monthly intervals chest x-ray or CT scans were made up to 2 years after CCRT. Medical records of the patients were retrospectively reviewed. The PT and/or LN progression were classified based on follow-up records and scans by two physicians. The volume of each separate lesion on the planning CT and their SUVmax from the pre-RT staging PET scan were then tested as prognostic factors for disease progression using Cox proportional hazard model with patient as random effect. Data were analyzed using R, package “coxme”.Results
A total of 291 PTs (8 patients had no PT, 252 had 1 PT, 18 had 2 PTs, 1 had 3 PTs) and 627 LNs (59 patients without LN, 57 had 1 LN, 57 had 2 LNs and 106 had >=3 LNs involved) were analyzed. The majority (92%) of the patients had TNM stage III and 86% patients had ≥N2. At a median follow-up of 30 months (95%CI 27-35) and median OS of 25 months (95% CI 21-29), 47 PTs had progression and 14 LNs had progression, 38% patients had systemic relapse. The log(Vol), SUVmax and lesion type (TP vs. LN) were each significant (p<0.001) as prognostic factor for progression in the univariate cox regression. In the multivariate analysis, log(Vol) remains as a significant predictor (p<0.001) with a trend toward significance for lesion type (p=0.07) (Figure 1). Figure 1Conclusion
Our regimen of 66 Gy in 24fx results in excellent local-regional control in locally advanced NSCLC patients. The PT yields a significantly higher risk of progression than LNs. A larger lesion volume and higher SUVmax were associated with an increased risk of progression.
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P2.12 - Poster Session 2 - NSCLC Early Stage (ID 205)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:
- Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P2.12-005 - Results of radical treatment of non-small cell lung cancer patients with a single synchronous metastasis (ID 1103)
09:30 - 09:30 | Author(s): J. Belderbos
- Abstract
Background
Stage IV non-small cell lung cancer (NSCLC) patients are considered incurable and mainly treated for palliation. The purpose of this study is to investigate the overall survival (OS) and disease free survival (DFS) of NSCLC patients, diagnosed with synchronous oligometastatic disease treated with curative intent of the intrathoracic disease as well as the metastasis.Methods
Patients treated between 2008 and 2013 were included in this retrospective analysis. Main inclusion criteria were: synchronous presentation of NSCLC and oligometastatic disease at diagnosis with only 1 extra-thoracic metastasis, and multidisciplinary consent on a radical treatment of both the intrathoracic disease and the solitary metastasis. Treatment of the intrathoracic disease consisted of radical radiotherapy (> 55 Gy biological effective dose) or surgical resection. Treatment of the metastasis consisted of radical/stereotactic radiotherapy or surgical resection or radiofrequency ablation (RFA).Results
Twenty-two patients, 13 men and 9 women, were included. The mean age was 61 years (range 41-79) and all were in good condition (WHO 0-1). The sites of the solitary metastases were brain (13), bone (6), liver (1), soft tissue (1) and adrenal gland (1). The intrathoracic tumor stage (ignoring M-status) was IA in 2 patients, IB in 1 patient, IIA in 4 patients, IIB in 1 patient, IIIA in 8 patients and IIIB in 6 patients. Nineteen patients were treated with radiotherapy and 3 patients had a surgical intervention for the primary tumor. Eighteen patients (82%) received chemotherapy, 3 concurrently and 15 sequentially. The metastases were treated with ablative/stereotactic radiotherapy (19), surgical intervention (2) and RFA (1). The median follow-up was 47 months (95% CI 24-69). Seventeen patients developed recurrent disease of whom 12 died. Only 2 recurrence occurred within the irradiated area. Both infield recurrences were brain metastasis after a stereotactic irradiation of 15 Gy and 18 Gy. The other recurrences where mostly pulmonary (7) and brain metastases (6). The median DFS was 14 months (range 1-47, 95% CI 9 – 19) and the median OS was 32 months (95% CI 12– 52). The 1- and 2-year OS was 78.7% (95% CI 52.7-91.5) and 59.5% (95% CI 32.8-78.5), respectively. The 1- and 2-year DFS was 54.5% (95% CI 30.5-73.2) and 24.9% (95% CI 8.1-46.3), respectively.Conclusion
Radical treatment of a highly selected group of NSCLC patients in good condition presenting with a single synchronous extra-thoracic metastasis resulted not only in adequate local control, but also in favorable long-term DFS and OS.
