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J.Y. Chang
Moderator of
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O10 - Stereotactic Ablative Body Radiotherapy (ID 104)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 8
- Moderators:H. Onishi, J.Y. Chang
- Coordinates: 10/28/2013, 16:15 - 17:45, Parkside 110 A+B, Level 1
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- Abstract
- Presentation
Background
To investigate the relationship between the different levels of biologically effective dose (BED) and the outcome of stereotactic body radiation therapy (SBRT) for Stage I non–small-cell lung cancer (NSCLC).Methods
Eligible studies were identified on Medline, Embase and the Cochrane Library from January 2001 to March 2013. According to the quartile of included studies, BED was divided into four dose groups: low (＜100Gy), medium (100–112.3Gy), medium to high (112.3–135Gy), high (>135Gy). To obtain pooled estimates of overall survival (OS), local control rate (LCR), cancer-specific survival(CSS), regional failure rate(RFR), distant failure rate (DFR)，data were combined in a random effect model. The difference in pooled estimate among BED groups was assessed with the Pearson chi-squared test. The meta-regression model was used to explore the relationship between the characteristics of the studies and the prognostic index.Results
Fifty-nine observational studies with a total of 5,562 patients were included in the meta-analysis. Pooled estimates of 2-year and 3-year OS in the medium BED (79%, 71%) group were higher than in the low (64%, 57%) or medium to high BED (69%, 57%) or high groups (66%, 56%), respectively (p＜0.001, p＜0.001, p＜0.001,respectively). Pooled estimates of 2-year LCR in the medium BED (89%) group was lower than in medium to high BED (94%)or high groups (94%), respectively (p=0.003,0.009 respectively). While no significant differences were observed between each two of four different levels of BED and the 3-year RFR.Conclusion
Based on the meta-analysis, a statistically significant OS benefit at 2 and 3 years can be demonstrated in the treatment of Stage I NSCLC with the delivery of medium BED compared with low, medium to high BED or high BED. The medium BED (range, 100–112.3Gy) for SBRT may currently be more beneficial and reasonable in Stage I NSCLC.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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O10.02 - Radiation Therapy Oncology Group (RTOG) protocol 0915: A randomized phase II study comparing 2 Stereotactic Body Radiation Therapy (SBRT) schedules for medically inoperable patients (pts) with stage I peripheral Non-Small Cell Lung Cancer. (ID 68)
16:25 - 16:35 | Author(s): G. Videtic, C. Hu, A. Singh, J. Chang, W. Parker, K. Olivier, S. Schild, R. Komaki, J. Urbanic, H. Choy
- Abstract
- Presentation
Background
To select the most favorable treatment regimen based on the rate of grade 3 or higher protocol-specified adverse events (psAEs) at 1 year.Methods
Pts with documented baseline medical conditions precluding lobectomy and biopsy-proven peripheral (greater than 2 cm from the central bronchial tree) T1/T2, N0 (clinically node negative by PET), M0 tumors were eligible. Patients (pts) were randomized to receive either 34 Gy in one fraction (arm 1) or 48 Gy in 4 consecutive once-daily fractions (arm 2). Rigorous central accreditation and quality assurance assessments were used to assure pts were treated according to protocol guidelines. The study was designed to detect whether psAEs rate>17% at a 10% significance level (1-sided) and 90% power. Secondary endpoints included primary tumor control (PC) rate, 1-year overall survival (OS), progression-free survival (PFS). The regimen selection criteria were based on pre-specified rules of psAEs and PC for each arm. Formal comparisons were not performed.Results
The study opened in September 2009 and closed in March 2011 after accruing a total of 94 pts. Median follow up was 20.6 months. Of 86 evaluable pts, 41 were in arm 1 and 45 in arm 2. Baseline pt and tumor characteristics were balanced between both arms. 4 (9.8%) pts on arm 1 (95% CI: 2.7-23.1%; p=0.151) and 6 (13.3%) pts on arm 2 (95% CI: 5.1-26.8%; p=0.337) experienced psAEs. 39 (95.1%) pts on arm 1 and 45 (100%) pts on arm 2 received planned SBRT treatment. Contouring compliance indicated 100% and 95.6% of targets and 89.5% and 82.2% of normal tissue structures were outlined per protocol/minor deviations, for arms 1 and 2, respectively. OS at 1 year was 85.4% (95% CI: 70.3-93.1%) for arm 1 pts and 91.1% (95% CI: 78.0-96.6%) for arm 2. PFS at 1 year was 78.0% (95% CI: 62.1-87.9%) for arm 1 and 84.4% (95% CI: 70.1-92.3%) for arm 2. The PC rates at 1 year were 97.1% (95% CI: 85.1-99.9%) for arm 1 and 97.6% (95% CI: 87.1-99.9%) for arm 2.Conclusion
At one year, 34 Gy in one fraction met pre-specified criteria with respect to adverse events and primary control, and therefore is selected as the experimental arm for a planned phase III trial. Supported by RTOG U10 CA21661 and CCOP U10 CA37422 grants from NCI.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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O10.03 - Safety of Endobronchial Implantation of Electromagnetic Fiducials for Real-time Tracking of Lung Tumors during Radiotherapy (ID 2040)
16:35 - 16:45 | Author(s): D.A. Nader
- Abstract
- Presentation
Background
Lung tumor control has improved with advances in radiotherapy delivery (RT). Respiratory motion inders improvements. An Anchored Beacon® transponder (Varian Medical Systems, Palo Alto, CA) can track lung tumors in real time during RT. This study evaluates the safety of these bronchoscopically implanted transponders in 50 lung tumor patients undergoing RTMethods
Each patient underwent implantation of 3 anchored transponders in the lung. A delivery catheter was inserted into the bronchoscope and using fluoroscopic guidance +/- radial endobronchial ultrsound (EBUS) and/or electromagnetic guidance (superDimension): the catheter was positioned in a 2-2.5 mm diameter airway, within 3 cm of the tumor. The transponder was deployed by depressing a plunger within the delivery catheter. The catheter was then withdrawn. CT's were acquired before RT and every 1-2 weeks during treatment. Transponder positions were measured.Results
50 patients (28 female/ 22 male) with median age 64 had transponders inplanted. Follow-up ranged from 0- 15.5 months (median 9.2). Positional stability of the Anchored transponders over the course of RT was confirmed. Inter-transponder distance from serial CT scans have been evaluated in 47 of 49 patients who underwent RT. Inter-transponder distances were stable over the course of radiation therapy for 140/141 (99%) of Anchored transponders. 2 Anchored transponders migrated, one after completion of RT. Safety: 2 patients (4%) sustained pneumothorax with insertion. Each resolved within one day with chest tube placement and withdrwal. One patient sustained a cardiac arrest prior to bronchoscopy for implantation. 2/147 (1%) sustained migration. Patient A coughed one transponder. which was placed in too large and proximal airway. Patient B was found the have the transponder migrating to the pleural space associated with a suppurative lung infection 3 months post-treatment.Conclusion
Bronchoscopic implantation of Anchored transponders can be performed with few complications. Anchored transponders are positonally stable in the lung with a 99% retention rate. There are multiple advantages to real-time localization and tracking of lung tumors. The Anchored transponder demonstrated a high safety profile and significantly low migration.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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O10.04 - DISCUSSANT (ID 3929)
16:45 - 17:00 | Author(s): U. Ricardi
- Abstract
- Presentation
Abstract not provided
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- Abstract
- Presentation
Background
Stereotactic ablative radiotherapy (SABR) is now a guideline-recommended treatment for early-stage lung cancer (ES-NSCLC), achieving 5-year local control rates of approximately 10%. The timely detection of local recurrence (LR) and early salvage following SABR is impaired by fibrotic changes, which occur commonly. Seven high-risk CT features (HRFs) that suggest LR include; enlarging opacity, cranio-caudal growth, sequential enlarging opacity, enlarging opacity after 12 months, bulging margin, loss of linear margin and loss of air bronchograms. We validated these, performing blinded clinician assessment in patients with and without LR.Methods
ES-NSCLC patients treated with SABR, who developed pathology-proven LR (n=12), were matched 1:2 to patients without clinical LR (n=24), based on tumor location, SABR fractionation, PTV size and follow-up duration. Three radiation oncologists assessed serial follow-up CT images for HRFs, while blinded to outcomes. The sensitivity and specificity of HRFs and combinations of these were determined.Results
The median follow-up was 24 months (range 6-67) and both cohorts were well matched. All HRFs were significantly associated with LR (p≤0.002), Table 1. The best individual predictor of LR was opacity enlargement after 12 months (100% sensitivity, 83% specificity), however this was detected slowest, at a median 22 months. The earliest HRF detected was cranio-caudal growth detected at a median 13 months. The HRFs enlarging opacity and cranio-caudal growth were each detected at least 3 months prior to the actual diagnosis of LR 42% of the time. The odds of LR increased 4-fold for each additional HRF detected (p<0.001). The sensitivity and specificity of detecting multiple HRFs is shown in Table 2, with ≥3 HRFs being the best predictor of LR (sensitivity 92%, specificity 92%). Figure 1 Figure 2Conclusion
LR following SABR can be accurately predicted by the presence of HRFs on surveillance CT scans. This approach may reduce unnecessary confirmatory procedures, and facilitate earlier salvage treatment.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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O10.06 - Inter-Rater Reliability of the Categorization of Late Radiographic Changes after Lung Stereotactic Body Radiation Therapy (SBRT) (ID 1901)
17:10 - 17:20 | Author(s): S. Faruqi, M. Giuliani, H. Raziee, M.L. Yap, H. Roberts, L. Le, A. Brade, B.C.J. Cho, A. Sun, A. Bezjak, A. Hope
- Abstract
- Presentation
Background
Radiographic changes following lung SBRT have been previously categorized into 4 groups: modified conventional pattern (A), mass-like fibrosis (B), scar-like fibrosis (C) and no evidence of increased density (D) (Dahele et al.).The purpose of this study was to assess the inter-rater reliability of this categorization in patients with early stage non-small cell lung cancer.Methods
79 patients treated with SBRT for early stage NSCLC at a single institution who had a minimum follow-up of 6 months were included in this study. Serial post-treatment CT images were presented to expert clinicians (up to 6) familiar with post-SBRT radiographic changes and were scored by each individual in a blinded fashion according to the published categorization of A, B, C or D. The proportion of patients categorized as A, B, C or D at each interval was determined. Krippendorff's alpha (KA) was used to establish inter-rater reliability at each time point. A leave-one-out analysis was performed at each time point on each rater to determine the sensitivity of the KA score to an individual rater. To explore if a training effect existed the KA of the first and last 20 patients scored by the raters was determined.Results
There were 351 ratings on 67 patients at 12mo, 250 ratings on 49 patients at 24mo, 169ratings on 31 patients at 36mo and 80 ratings on 14 patients at 48mo. The proportion of patients scored in each category of A,B,C &D is reported in Table 1. Table 1: Scale Category by Time-Point
Category A was the most common at all time points except 48 months when category C was the most common. KA was 0.28, 0.27, 0.18 and 0.27 at 12, 24, 36 and 48 months respectively. The range of KA in the leave-one-out analysis was 0.25-0.31, 0.24-0.27, 0.15-0.22 and 0.24-0.31 at 12, 24, 36 and 48 months respectively. The KA of the first 20 patients vs the last 20 patients was 0.34 vs 0.47 at 12 months.A (Modified-Conventional) B (Mass-like Fibrosis) C (Scar-like Fibrosis) D (No Evidence of Increased Density) 6 months 43% 9% 6% 42% 12 months 50% 16% 11% 23% 18 months 46% 18% 16% 20% 24 months 46% 22% 17% 15% 36 months 40% 24% 21% 15% 48 months 29% 24% 31% 16% Conclusion
The predominant pattern of post SBRT radiographic changes evolves over time. In this study categorization of late post-SBRT radiographic changes has moderate inter-rater agreement. There is a suggestion of a training effect with more experience. However, categorization of late radiographic changes following SBRT is challenging and may require specific training.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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O10.07 - Dose-response analysis of radiation induced rib fractures after SBRT for NSCLC (ID 2690)
17:20 - 17:30 | Author(s): B. Stam, A. Scheenstra, J. Belderbos, H. Peulen, J. Nijkamp, J.J. Sonke
- 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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O10.08 - DISCUSSANT (ID 3930)
17:30 - 17:45 | Author(s): S. Senan
- Abstract
- Presentation
Abstract not provided
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Author of
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Symposium supported by IASLC Radiotherapy Group (ART): What is the Appropriate Patient Population for SBRT? (Simultaneous Translation English >< Mandarin provided) (ID 243)
- Event: WCLC 2013
- Type: Other Sessions
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 10/29/2013, 07:00 - 08:00, Parkside Auditorium, Level 1
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How I do it: Dose, volume, motion management - 1 (ID 5672)
07:00 - 07:20 | Author(s): J.Y. Chang
- Abstract
Abstract not provided
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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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MO17.11 - Stereotactic ablative radiotherapy (SABR) for centrally located early-stage or isolated parenchymal recurrences of non-small cell lung cancer (NSCLC): How to fly in a "no fly zone" (ID 1961)
17:15 - 17:20 | Author(s): J.Y. Chang
- Abstract
- Presentation
Background
SABR has become a standard treatment option for medically inoperable, peripherally located early-stage NSCLC. However, using SABR for centrally located lesions remains challenging because of the potential for severe side effects. Here we sought to validate our previous experience with SABR (50 Gy in 4 fractions) for central lesions, including the dose-volume constraints, and explore a new regimen of 70 Gy in 10 fractions for cases in which dose-volume constraints cannot be met with the previous regimen.Methods
We used 4D-based, volumetric image-guided SABR to treat 101 patients with biopsy-proven and PET/CT-staged centrally located (within 2 cm of bronchial tree, trachea, major vessels, esophagus, heart, pericardium, brachial plexus or vertebral body) T1-2N0M0 tumors (n=82) or isolated lung-parenchyma recurrent lesions (n=19). The treatment period spanned February 2005 through May 2011; follow-up visits (every 3 months for 2 years and every 6 months for the next 3 years) included chest CT or PET/CT. Endpoints were toxicity (CTCAE v3.0), survival, local control, regional control, and distant metastasis.Results
At a median follow-up time of 30.3 months for all patients (40.5 months for those alive), median overall survival time was 56.5 months and 5-year overall survival rate was 49.0%. Three-year actuarial local, regional, and distant control rates were 96.5%, 87.2% and 77.3%. The most common toxicities were chest-wall pain (18% grade 1 and 13% grade 2) and radiation pneumonitis (10.9% grade 2 and 1.9% grade 3). No patient experienced grade 4 toxicity and one patient with tumor invading bronchial tree who received 70 Gy in 10 fractions died from hemoptysis 13 months after SABR. The distance between tumor and chest was associated with chest wall pain (≤1 cm 45% vs >1 cm 17%, p=0.002). Univariate and multivariate analyses showed that for the 82 patients receiving 50 Gy in 4 fractions, mean total lung dose (MLD) >5 Gy or ipsilateral lung V~20~ (iV~20~) >16% were independent predictors of radiation pneumonitis; 3 of 9 patients in that group with D~max~ to brachial plexus >35 Gy experienced brachial neuropathy versus none of the 73 patients with brachial D~max~ ≤ 35 Gy (p=0.001).Conclusion
SABR for centrally located lesions produces clinical outcomes similar to those for peripheral lesions when normal tissue constraints are respected. For 50 Gy in 4 fractions, we recommend MLD ≤5 Gy, lung iV~20~ ≤16%; bronchial tree D~max~ ≤ 38 Gy, V~35~ ≤1 cm[3]; major vessel D~max~≤ 56 Gy, V~40~≤1 cm[3]; esophageal D~max~ ≤35 Gy, V~30~≤1 cm[3 ]; brachial plexus D~max~ ≤35 Gy, V~30~≤0.2 cm[3] and spinal cord D~max~ <25 Gy. Giving 70 Gy in 10 fractions is another option for challenging cases but can produce severe toxicity if significant amounts of critical structures are exposed to ≥70 Gy. Proper selection of cases (based on tumor location and normal tissue constraints) and SABR regimens and volumetric image-guided delivery are all crucial to avoid overdosing critical structures. Typically, a minimum 5-10 mm distance between critical structures and gross tumor is required to meet dose-volume constraints.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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P3.08 - Poster Session 3 - Radiotherapy (ID 199)
- Event: WCLC 2013
- Type: Poster Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P3.08-011 - Stereotactic Ablative Radiotherapy: A Potentially Curable Approach to Multiple Primary Lung Cancer (ID 1454)
09:30 - 09:30 | Author(s): J.Y. Chang
- Abstract
Background
Lung parenchymal recurrent or multiple lobe cancer is typically considered to have metastatic disease and treated with palliative approach such as chemotherapy. However, some of these patients may have multiple primary lung cancer (MPLC) that could be potential curable. Surgical resection has been the standard treatment for early-stage multiple primary lung cancer (MPLC). However, a significant proportion of patients with MPLC cannot undergo surgery. We explored here the role of stereotactic ablative radiotherapy (SABR) for patients with MPLC.Methods
We reviewed MPLC cases treated with SABR (50 Gy in 4 fractions) for the second tumor. Four-dimensional CT–based planning/volumetric image-guided treatment was used for all patients. Patients underwent chest CT scanning every 3 months for 2 years after the SABR and then every 6 months for another 3 years. PET scans were recommended at 3–12 months after SABR. Toxic effects were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Effects version 4.Results
For the 101 patients treated with SABR, at a median follow-up interval of 36 months and median overall survival of 46 months, 2-year and 4-year in-field local control rates were 97.4% and 95.7%. 2- and 4-year rates of overall survival (OS) were 73.2% and 47.5% and progression-free survival (PFS) were 67.0% and 58.0%. Patients with metachronous tumors had higher OS and PFS than did patients with synchronous tumors (2-year OS 80.6% metachronous vs. 61.5% synchronous; 4-year OS 52.7% vs. 39.7%; p=0.047; 2-year PFS 84.7% vs. 49.4%; 4-year PFS 75.6% vs. 30.4%; p=0.0001). For patients whose tumors were both of the same histology (meaning that the second lesion could have been a satellite, a metastasis, or a recurrent lesion), the 2-year and 4-year OS rates were 76.4% and 51.2%, which were no different from the OS rates for patients with tumors of different pathology (2-year OS: 66.7% and 4-year OS: 40.5%; p=0.406). The 2- and 4-year OS of patients in whom both tumors were classified as stage I were 76.1% and 55.2%, which was better than the OS rates for the patients whose index tumors were of higher stage (2-year OS 66.7%, 4-year OS 26.6%; p=0.049). For patients whose index tumor was treated with surgery or SABR, the incidence of grade ≥3 radiation pneumonitis was 3% (2/71), but this increased to 17% (5/30) for patients whose index tumor was treated with conventional radiotherapy. Other grade ≥3 toxicities included grade 3 chest wall pain (3/101, 3%) and grade 3 skin toxicity (1/101, 1%).Conclusion
1. SABR achieves an excellent long-term tumor control and promising PFS and OS in early-stage MPLC. 2. Toxicity could happen but within the scope of SABR in stage I disease. 3. Caution should be taken integrating SABR with prior conventional radiotherapy for stage II/III disease. SABR could be an effective alternative to surgery for curative treatment of early-stage MPLC tumors.
