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A. Sun
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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. Sun
- 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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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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MO17.03 - Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated with SBRT: A Case-Matched Analysis (ID 2024)
16:25 - 16:30 | Author(s): A. Sun
- Abstract
- Presentation
Background
Reported non-small cell lung cancer (NSCLC) nodal failure rates following stereotactic body radiotherapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesize that this effect is due to incidental prophylactic nodal irradiation.Methods
A prospectively collected group of medically inoperable early stage NSCLC patients (n=179) from 2004 to 2010 was used to identify a patient cohort with nodal relapses (n=19). These cases were matched, 1:2, to controls, controlling for tumour volume (i.e. same or greater) and tumour location (i.e. same lobe). Reference (normalized total) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical record. Multivariate logistical regression analyses determined variables of interest.Results
The case and control cohorts were well matched with respect to age, sex, method of nodal staging, SUVmax, histology subtype, dose and length of follow up.. The controls, as expected, had larger gross tumour volumes (p=0.02). The mean hilar doses were 9.6 and 22.4 Gy for cases and controls, respectively (p=0.014). Similarly, the mean carinal doses were 7.0 and 9.2 Gy, respectively (p=0.13). The mean ipsilateral hilar doses were 19.8 and 3.6 Gy for ipsilateral non-hilar and hilar nodal relapses, respectively (p=0.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse (Figure 1).Figure 1Conclusion
Incidental hilar dose greater than 20 Gy (normalized to 2Gy/fraction) appears to be correlated with lack of hilar relapses in inoperable early stage NSCLC patients treated with SBRT.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. Sun
- 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. Sun
- 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. Sun
- 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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P2.08 - Poster Session 2 - Radiotherapy (ID 198)
- Event: WCLC 2013
- Type: Poster Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 2
- Moderators:
- Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P2.08-004 - Impact of medical co-morbidities on survival in patients treated with stereotactic body radiotherapy for early stage non-small cell lung cancer (ID 827)
09:30 - 09:30 | Author(s): A. Sun
- Abstract
Background
Stereotactic body radiotherapy (SBRT) is an effective treatment for early stage inoperable non-small cell lung cancer (NSCLC), with loco-regional control of 80-90%. However, the median overall survival of these patients is limited. We evaluate the impact of co-morbidities on patient survival and whether a subset of patients who may not benefit from SBRT can be identified.Methods
Patients treated on a prospective protocol at a single cancer center with SBRT for T1-T2N0 NSCLC from Oct 2004-May 2012 were evaluated. The most common doses delivered were 48Gy/4fr and 54Gy/3fr. The presence of significant medical co-morbidities including cardiac disease, COPD, cerebro-vascular disease, diabetes, previous pneumonectomy and oxygen dependence were recorded at baseline. Patient, tumor, and treatment data as well as outcomes were prospectively collected. Log rank tests were performed for survival analysis and chi squared tests used to analyze deaths within 1 year from radiotherapy treatment (D<1y). Cancer specific deaths (CSD) were defined as any death following a recurrence of the previously treated NSCLC.Results
There were 279 patients identified, 134 female (48%) and 145 male (52%). The median age was 76 years (range 48-93). The performance status was ECOG 0 in 87 patients (31%), ECOG 1 in 127 patients (46%), ECOG 2 in 53 patients (19%) and ECOG 3 in 9 patients (3%). There were 212 (76%) with T1 tumors, the remainder (24%) T2 tumors. The median follow up was 1.3 years. At last follow up, 111 patients (40%) had died, including 42 (15%) patients with D<1y. Of all deaths, 25 (22.5%) were CSD, the remainder from other causes. There were 222 patients (80%) identified as having a significant co-morbidity, collectively these conditions did not influence deaths from any cause (DAC) or CSD. The presence of cardiac disease (N=67) led to an increased risk of DAC (HR 4.1, p = 0.04) but not CSD (HR 1.2, p=0.28). These results were more pronounced for D<1y, patients with cardiac disease having increased D<1y, (HR 7.34, p=0.007), but not CSD<1y, (HR 2.9, p=0.09). Other co-morbidities were not correlated of survival. ECOG status was correlated with both DAC (HR 15.1, p=0.005) and CSD (HR 9.3, p=0.05).Conclusion
The presence of respiratory and vascular co-morbidities should not necessarily preclude a patient from receiving SBRT. ECOG status and prognosis from a cardiac point of view may be associated with poorer overall survival at 1 year and should be considered when assessing a patient’s suitability for SBRT. -
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P2.08-005 - 4D-PET/CT-based adaptive dose escalated radiotherapy (RT) in locally advanced non-small cell lung cancer (LA-NSCLC) (ID 1171)
09:30 - 09:30 | Author(s): A. Sun
- Abstract
Background
There has been recent interest in dose escalation in LA-NSCLC, with the aim to improve both loco-regional control and overall survival. Attempts to dose escalate CT-defined volumes for radiotherapy (RT) for LA-NSCLC have been limited due to organ at risk (OAR) toxicity. We investigated the potential for adaptive dose-escalation to PET-defined volumes, using 4DPET/CT scans acquired prior to and during a course of radical chemo/RT (CRT).Methods
This single institution study prospectively enrolled patients with NSCLC receiving CRT to a dose ≥60Gy, delivered in daily 2Gy treatments. 4DPET/CT scans were acquired prior to (week 0) and at weeks 2 and 4 during RT. RT was delivered using the intensity modulated RT (IMRT) plan developed from the week 0 scans. Three alternative dose escalated IMRT plans were developed offline based on the week 0, 2 and 4 scans. The PET avid primary (PET-T) and nodal disease (PET-N) volumes were auto-contoured using the 50%SUV~max~ metric. PET-T and PET-N were dose escalated to as high as possible while respecting OAR constraints and ensuring coverage of the clinical plan PTV. The D95% and D~max~ of the PET-T and PET-N were calculated and compared between week 0-2-4.Results
Thirty-two patients were recruited, with 27 completing all scans. Sixteen patients were stage IIIA (60%), 9 were IIIB (33%) and 2 were IIA (7%). Eight patients (30%) had been prescribed a clinical dose of 60 Gy, 17 (63%) had 66 Gy, 1 patient 70Gy and 1 patient 74Gy. 25 patients (93%) were boosted successfully above the clinical plan doses at week 0; this reduced to 23 (85%) at week 2 and 20 (74%) at week 4. For all weeks combined, the D95 for PET-T was higher than that delivered to clinical PTV by a median of 16.2 Gy (4.2-37.4Gy). The D95 for PET-N exceeded that delivered to clinical PTV by 13.4Gy (6.8-29.7Gy). The median D95% to the PET-T at week 0, 2 and 4 were 74.4 Gy, 75.3Gy and 74.1Gy respectively. The median D~max~ to PET-T at week 0, 2 and 4 were 85.9Gy, 83.8Gy and 81.2Gy. The median D95% to PET-N at week 0, 2 and 4 was 74.3Gy, 71.0Gy and 69.5Gy. The median D~max~ to PET-N at week 0, 2 and 4 were 82.7Gy, 82.5Gy and 78.9Gy.Conclusion
Using 4DPET/CT derived volumes, it is feasible to dose escalate a majority of patients, either at the onset or during RT. Though the PET-T was able to be escalated to higher doses than PET-N, nodal disease can still be boosted to significant doses. More patients were able to be dose escalated at the onset of RT; however mid-RT dose escalation allows the additional potential for adaptation.
