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A. Bezjak
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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 - 2 (ID 5671)
07:20 - 07:40 | Author(s): A. Bezjak
- Abstract
Abstract not provided
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HOD4 - Tuesdays Highlights of the Day - Medical Oncology, Biology, Radiotherapy and Combined Modality (ID 228)
- Event: WCLC 2013
- Type: Highlight of the Day Session
- Track: Biology
- Presentations: 1
- Moderators:J.V. Heymach
- Coordinates: 10/30/2013, 07:00 - 08:00, Bayside Auditorium B, Level 1
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HOD4.2 - Radiotherapy and Combined Modality (ID 4045)
07:20 - 07:50 | Author(s): A. Bezjak
- Abstract
- Presentation
Abstract not provided
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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MO14 - Mesothelioma II - Surgery and Multimodality (ID 121)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Mesothelioma
- Presentations: 1
- Moderators:E. Lim, B. McCaughan
- Coordinates: 10/29/2013, 10:30 - 12:00, Bayside Gallery B, Level 1
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MO14.12 - Neoadjuvant Hemithoracic Intensity Modulated Radiotherapy: The "SMART" Approach for Managing Malignant Pleural Mesothelioma (ID 2328)
11:30 - 11:35 | Author(s): A. Bezjak
- Abstract
- Presentation
Background
Management of malignant pleural mesothelioma (MPM) remains controversial. After extra-pleural pneumonectomy (EPP) and adjuvant radiotherapy, many fail distantly (peritoneal cavity, contralateral lung), possibly due to inadvertent tumour spillage at time of EPP. We hypothesize that neoadjuvant radiation followed by planned imminent EPP can limit the proliferation of clonogens spilt intraoperatively. The radiotherapy technique developed for the Surgery for Mesothelioma After Radiation Therapy (SMART) study is described.Methods
We conducted a phase II prospective REB approved single cohort clinical feasibility study on surgically resectable stage T1-3N0M0 MPM. The pre-operative clinical target volume (CTV) was defined as the ipsilateral hemithorax, , including biopsy and drainage tract sites. The gross tumour volume (GTV) was defined as any tumour seen on imaging. The dose prescription to the CTV was 25 Gy in 5 daily fractions over approximately 1 week with a concomitant boost of 5 Gy to the GTV and tract sites. All patients underwent EPP within 1 week of completing the neoadjuvant RT. If ypN2 found, patients were offered adjuvant chemotherapy. Treatment related toxicity was defined by the CTCAE v3.Results
The accrual goal of 25 patients was completed between Nov 2008 and Oct 2012. All completed their intended RT and EPP. IMRT was well tolerated with only grade 1-2 toxicities noted (fatigue, nausea, and esophagitis). EPP was performed 6±2 days after completion of IMRT. Dosimetric values are shown in the table below.Dosimetric Parameter dose max (cGy) 3290.5 CTV>2750 cGy (%) 95.5 CTV>2300 cGy (%) 97.8 PTV>2750 cGy (%) 93.3 PTV>2300 cGy (%) 91.7 LUNG>700 cGy 4.9 LUNG mean (cGy) 315.0 LIVER>1400 cGy (%) 45.3 LIVER mean (cGy) 1371.8 HEART>1400 cGy (%) 50.3 HEART mean (cGy) 1473.7 contra KIDNEY>750 cGy (%) 19.6 contra KIDNEY mean (cGy) 318.1 ipsi KIDNEY>750 cGy (%) 49.5 ipsi KIDNEY mean (cGy) 561.6 ESOPHAGUS 2880.1 CANAL max (cGy) 2026.1 prv3mmCANAL max (cGy) 2125.4 Conclusion
Short neoadjuvant hemithoracic radiotherapy (30 Gy in 5 daily fractions over 1 week) using the SMART protocol constraints are well tolerated. The SMART protocol is technically demanding, requiring very close and careful coordination and planning between the multiple disciplines.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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MS08 - SABR (ID 25)
- Event: WCLC 2013
- Type: Mini Symposia
- Track: Radiation Oncology + Radiotherapy
- Presentations: 1
- Moderators:U. Ricardi, J. Belderbos
- Coordinates: 10/29/2013, 14:00 - 15:30, Parkside Ballroom B, Level 1
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MS08.1 - Is SABR Safe for Central Disease? (ID 491)
14:05 - 14:25 | Author(s): A. Bezjak
- Abstract
- Presentation
Abstract
There has been an explosion of studies, reports and clinical experience with Stereotactic Ablative Body Radiotherapy (SABR) for lung lesions (both primary and metastatic). Most of the experience and published literature focuses on peripheral lesions; the published and used SBRT dose/fractions are safe, associated with virtually no acute toxitxity and very low rates of subacute and late RT toxicity and high rates of local control. There is an emerging experience in treating central lesions, previous described as a "no-fly zone" . There is also an emerging appreciation about the multitude of organs at risk -- the intiial focus was on bronchi and spinal cord, but clinicians and researchers need to be midful of esophagus, great vessels, heart and brachial plexus as well. The presentation will review the current state of knowledge and highlight the methodological challenges of interpreting the current literature, and emphasize the importance of careful followup of patients with more centrally located lesions, treated with SABR.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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O01 - Prognostic and Predictive Biomarkers I (ID 94)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:T. Mitsudomi, V. Gregorc
- Coordinates: 10/28/2013, 10:30 - 12:00, Parkside Auditorium, Level 1
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O01.01 - Genetic polymorphisms of inflammatory and DNA repair pathways, radiation-related esophagitis and pneumonitis in definitive chemoradiation treated non-small cell lung cancer patients. (ID 2997)
10:30 - 10:40 | Author(s): A. Bezjak
- Abstract
- Presentation
Background
The benefits of concurrent chemoradiotherapy in locally advanced non-small cell lung cancer (NSCLC) are tempered by treatment toxicity. Germline genetic variants have been associated with intrinsic radiosensitivity and radiotoxicity in various cancer settings. We investigated whether variants in genes involved in inflammation response and DNA repair pathways independently influence radiation-induced phenotypes of esophagitis and pneumonitis. From 19 candidate genes, 52 polymorphisms, directed by literature and by tagging procedures, were systematically selected for assessment. The candidate genes were involved in DNA repair (double-strand breaks, homology directed, nucleotide excision) and pro/anti-inflammatory signaling. The this investigation sought to evaluate the association of genetic sequence markers for two clinically significant radiation-induced toxicities - esophagitis and pneumonitis – seen in NSCLC patients treated with a curative intent.Methods
From 312 patients treated at PMCC between 2005-12, a training cohort was defined consisting of 92 definitive concurrent chemoradiation/radiation-treated NSCLC patients with genotype information on the 52 polymorphisms. A second, validation cohort consisted of 209 patients. Multivariate logistic regression was performed for each polymorphism of interest, adjusting for known clinical and dosimetric prognostic factors on the dichotomized outcomes of radiation esophagitis (Grades 0-2 vs 3-5) and pneumonitis (Grades 0-1 vs 2-5). The CTCAEv4.03 grading criteria were used. Additive genetic models were used for genetic association analysis. In the training set, genetic variants, genotyped by IlluminaGoldenGate, with p<=0.05 were identified for validation; HWE was set at p>0.01, a criteria met by all polymorphisms with statistical significance.Results
In the combined training and validation datasets, 63% were males, with median age of 65 years. Specifically in the training dataset, 65% were male, with median age of 62, median mean lung doses of 15.9, median max esophageal dose of 67.1 and median V20 of 27.6. For esophagitis, the final models were adjusted for concurrent chemotherapy, V20 and max esophageal dose. Five genetic variants linked to TNF and IL6 were significantly associated with outcome (each using wild-type genotype as reference) (Table 1). For pneumonitis, the final models adjusted for V20 and smoking status. Eight genetic variants found within four genes (ATM, BRCA2, IL1alpha, IL1RN) were associated with significant pneumonitis (Table 1).ESOPHAGITIS Function / Pathway Gene refSNP OR 95% CI P value pro-inflammatory cytokine TNF rs3093662 3.54 1.9-10.6 0.02 pro-inflammatory cytokine TNF rs3093664 3.42 1.2-10.2 0.03 pro-inflammatory cytokine TNF rs3093665 4.95 1.2-21.1 0.03 anti-inflammatory cytokine IL6 rs1800797 2.53 1.0-6.2 0.04 anti-inflammatory cytokine IL6 rs1800795 2.45 1.0-5.9 0.046 PNEUMONITIS Function / Pathway Gene refSNP OR 95% CI P value double-strand break repair ATM rs664143 2.67 1.3-5.6 0.01 double-strand break repair ATM rs664677 2.37 1.2-4.7 0.01 homology-directed repair BRCA2 rs1799955 2.59 1.3-5.3 0.01 homology-directed repair BRCA2 rs1801406 2.42 1.2-4.8 0.01 homology-directed repair BRCA2 rs1799943 2.09 1.0-4.2 0.04 anti-inflammatory cytokine IL1alpha rs17561 2.63 1.2-5.7 0.01 anti-inflammatory cytokine IL1alpha rs2856863 2.60 1.1-5.9 0.02 anti-inflammatory cytokine IL1RN rs3087263 0.17 0.04-0.8 0.04 Conclusion
In our 92 patient training set, genetic variations in TNF and IL6 are associated with radiation esophagitis, while genetic variations in ATM, BRCA2, IL1alpha and IL1RN are associated with pneumonitis. Results from the 209 patients in the validation dataset will be presented at the meeting (A.H. and G. L are co-senior authors).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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O10.06 - 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): A. Bezjak
- 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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P1.08 - Poster Session 1 - Radiotherapy (ID 195)
- Event: WCLC 2013
- Type: Poster Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P1.08-019 - Late Radiographic Changes After Lung Stereotactic Body Radiotherapy: Piloting a Recurrence Scale and a Synoptic Reporting Scale (ID 2209)
09:30 - 09:30 | Author(s): A. Bezjak
- Abstract
Background
Radiographic lung changes after Stereotactic Body Radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) are difficult to interpret. The reliability of previous scoring systems and their relationship to local failure has not been assessed. The purpose of this study was to design a synoptic radiographic scale for characterizing late radiographic changes after SBRT and to determine the inter-rater reliability of the scale.Methods
A Recurrence Scale (RS) was developed among lung radiation oncology/SBRT experts at a single institution, and a Synoptic Radiographic Scale (SRS) was designed in collaboration with an expert thoracic radiologist. For the RS, the suspicion for local recurrence on CT images was scored on a 5 point scale: 1) complete response, no recurrence; 2) fibrosis, not suspicious for recurrence; 3) fibrosis/mass, indeterminate for recurrence; 4) fibrosis/mass, suspicious for recurrence and 5) biopsy proven recurrence. On the SRS, CT changes were scored as ‘increasing’, ‘stable’, ‘decreasing’, ‘no change’ or ‘obscured’, along five dimensions: changes in the primary tumor site, involved lobe, consolidation, ground-glass opacity, and volume loss. Early stage NSCLC patients treated with SBRT at the institution with a minimum follow-up of 6 months were included. Serial post-treatment CT images at 12, 18, 24, 36, and 48 months were presented to the expert group (up to 6) who scored both scales in a blinded fashion. Krippendorff's alpha (KA) was used to assess inter-rater reliability. The association between RS score and known local failure was compared using Fisher’s Exact Test. The association between ‘growing tumor’ on the SRS and known local failure was compared using Fisher’s Exact Test.Results
79 patients were scored; 7 of them had documented local failures. Experts did 11243 scorings in total, ranging from 2351 at 6 months to 480 at 48 months. For the RS, the KA was 0.27, 0.36, 0.23 and 0.45 at 12, 24, 36 and 48 months respectively. For the SRS, KA was 0.22, 0.14 and 0.11 for the treated tumor at 12, 24 and 48 months and 0.33, 0.36 and 0.22 for consolidation at 12, 24 and 36 months. The tumor was scored as obscured in 40% of patients by 24 months. Of patients with local failure, 71% were at least once scored as ‘suspicious for recurrence’ by at least one rater, compared to 28% in patients without failure (p = 0.03). 86% of patients with failure were scored at least once as increased opacity in tumor site by at least one of raters, compared to 35% in patients without failure (p = 0.01).Conclusion
The RS has a significant relationship with local failure, and there is fair inter-agreement among experts on the suspicion of recurrence following SBRT. The SRS has low inter-rater reliability. Among its categories, only an increase in the opacity of treated tumor site is significantly related to failure. With future refinement of SRS categories, it can be a useful tool to standardize post-SBRT radiology reporting.
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P1.15 - Poster Session 1 - Thymoma (ID 189)
- Event: WCLC 2013
- Type: Poster Session
- Track: Thymoma & Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P1.15-009 - Outcomes and Predictors of Recurrence in Patients Treated with Risk-adapted, Post-operative Radiotherapy (RT) for Thymoma - A Single Institution, 30 Year Retrospective Study (ID 3124)
09:30 - 09:30 | Author(s): A. Bezjak
- Abstract
Background
Thymoma is a rare epithelial cell tumour of the thymus, with an incidence of 0.15 per 100 000 persons. Thymic carcinomas comprise a distinct subset and have a greater propensity for capsular invasion and distant metastases when compared to thymomas. Resection is the standard of care for localized disease but local recurrence is generally incurable, thus post-operative RT is often employed for high risk cases. The optimal dose of RT has not been established, nor whether lower doses can be utilized in a risk-adapted fashion for cases where RT is recommended but the aggressiveness of the disease/risk of recurrence is felt to be at the lower end of the spectrum. Use of lower dose RT may help reduce the chances of late RT toxicity. Our institution employs such a risk adapted strategy and we present here our long term results.Methods
Princess Margaret Cancer Center radiation and surgical oncology databases were queried from 1983-2012. Retrospective analyses using electronic patient records and Mosaiq radiotherapy database were performed to assess demographic data, clinical presentation and treatment. Descriptive statistics were used to report demographic data. Time to event analyses and correlation of outcomes with demographic and treatment variables are planned.Results
Details on 104 patients treated with post-operative radiotherapy from 1983-2012 were available. The mean age was 52, range 29-73. Of patients assessed, 55/104 were male. Masaoka-Koga stage was assessed: 6% of patients were stage I, 31% IIA, 21% IIB, 27% III, 10% IV and 6% unknown. The most common WHO grade was B2 (37%) followed by B1 (16%). Complete surgical resection (R0) was obtained in 72% patients, R1 in 21%, R2 in 2% and 5% unknown. Radiotherapy doses ranged from 40 Gy – 66 Gy delivered in daily 2 Gy fractions; 57% patients were deemed low risk (typically R0 resection and WHO grade B2 or lower) and received 40Gy while 36% received between 45-66Gy. Neoadjuvant or adjuvant chemotherapy was delivered to 13% of all patients. The mean follow up period was 9.4 years, range 0.5-25.5 years, during which 22% patients experienced relapse. Of these, 43% experienced regional recurrence, defined as an intrathoracic relapse in an area not-contiguous with the thymic bed or original tumour; 39% local (intrathoracic relapse contiguous with original disease or thymic bed), and 17% distant recurrence defined as extrathoracic or intraparenchymal pulmonary nodules. For patients that experienced relapse, the median time to relapse was 8.7 years (range 1.3-18.3 years). Of the 59 patients who received 40 Gy/20 fractions, 8 developed local relapse (13.5%). Overall survival and multivariable analyses will be reported as will assessment of long term toxicities.Conclusion
Risk-adapted RT prescription for patients with resected thymoma appears efficacious, and may result in an improved therapeutic ratio for these patients. Long-term, randomized controlled trials are required to further identify patients that are best suited to this approach.
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P3.07 - Poster Session 3 - Surgery (ID 193)
- Event: WCLC 2013
- Type: Poster Session
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P3.07-038 - Long-term outcome after resection of non-small cell lung cancer invading the thoracic inlet (ID 2929)
09:30 - 09:30 | Author(s): A. Bezjak
- Abstract
Background
Non-small cell lung cancer (NSCLC) of the thoracic inlet accounts for less than 5% of all lung cancers. Due to the lack of efficient treatment and the complexity of the anatomical structures commonly invaded, these tumors were deemed historically unresectable and fatal. In this study, we reviewed our surgical experience and long-term outcome after resection of NSCLC invading the thoracic inletMethods
All consecutive patients from a single center who underwent resection of NSCLC invading the thoracic inlet were reviewed with data retrieved retrospectively from the charts.Results
A total of 65 consecutive patients with a median age of 61 years (range 32 to 76) underwent resection of NSCLC invading the thoracic inlet from 1991 to 2011. Tumors were located in the previously described (Reference) five zones of the thoracic inlet as follows: zone 1 or anterolateral (n=5, 8%), zone 2 or anterocentral (n=7, 11%), zone 3 or posterosuperior (n=12, 18%), zone 4 or posteroinferior (n=22, 34%) and zone 5 or inferolateral (n=7, 11%). Fifty-two (80%) patients had induction therapy, mostly two cycles of cisplatin-etoposide and 45 Gy of concurrent radiation. All patients underwent en bloc resection of the lung and chest wall. Lobectomy was performed in 60 patients (92%). A median of three ribs were resected (range 1 to 5) and included the first rib in all patients. Twenty-four patients (37%) had an additional vertebral resection of up to five levels (median 3). Considering the most extended vertebral resection, total vertebrectomy with anterior-posterior spinal stabilization was required in 6 patients (25%), hemi-vertebrectomy with posterior spinal stabilization in 15 (62%), and partial vertebrectomy without stabilization in 3 (13%). Arterial resections were performed in seven patients (11%) and included subclavian artery (n=5), vertebral artery (n=1) and combination of sublclavian and carotid arteries (n=1).The median postoperative length of stay was 11 days (range 4 to 173). Postoperative morbidity and mortality were 46% and 6%, respectively. Pathologic response to induction treatment was complete (n=19) or near complete (n=12) in 31 patients (49%). Pathologic stages were 0 in 19 patients (29%), IB in 1 (2%), IIB in 28 (43%), IIIA in 15 (23%) and IIIB in 2 (3%) patients. After a median follow-up of 20 months (range 0 to 193), 34 patients were alive without recurrence. The overall 3- and 5-year survivals reached 58% and 52%, respectively. Results of the Cox regression and log-rank/Breslow tests identified the site of tumor (zone 1/3 vs 2/4/5, p=0.050) and the response rate to induction treatment (complete/near complete vs partial, p=0.004) as significant predictors of survivals. A trend toward shorter survival was found in case of arterial resection (p=0.063).Conclusion
Survival after resection of NSCLC invading the thoracic inlet in highly selected patients reached 52% after five years. Tumor location within the thoracic inlet and pathologic response to induction therapy were significant predictors of survivals. Reference: de Perrot M, Rampersaud R. Surgical approaches to apical thoracic malignancies. J Thorac Cardiovasc Surg. 2012 Jul;144(1):72-80.
