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A. Hope



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    MO14 - Mesothelioma II - Surgery and Multimodality (ID 121)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 2
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      MO14.09 - 5-year experience with accelerated induction hypofractionated hemithoracic intensity modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) (ID 2022)

      10:30 - 12:00  |  Author(s): A. Hope

      • Abstract
      • Presentation
      • Slides

      Background
      Our experience in tri-modality therapy for MPM with induction chemotherapy followed by EPP and high dose hemithoracic radiation demonstrated that completion of EPP and radiation provided the best results. We therefore developed a new protocol of accelerated induction hypofractionated hemithoracic IMRT followed by EPP to deliver optimal radiation to the whole tumor bed in a short period of time. EPP is performed approximately one week after completion of radiation to limit the risk of pneumonitis. The results of Surgery for Mesothelioma After Radiation Therapy (SMART) was reviewed and compared to our previous cohort of patients undergoing induction chemotherapy followed by EPP and adjuvant hemithoracic radiation.

      Methods
      All patients undergoing EPP in our institution between 01/2001 and 06/2013 were reviewed. The SMART protocol (25 Gy in 5 daily fractions over 1 week delivered to the entire ipsilateral hemithorax by IMRT with concomitant boost of 5 Gy to volumes at high risk based on CT and PET scan findings) was started in 2008. EPP was performed 6±2 days after radiation therapy. The results of the SMART protocol were compared to the group of patients undergoing induction chemotherapy followed by EPP as part of a trimodality approach.

      Results
      A total of 111 patients underwent EPP between 01/2001 and 06/2013 with a hospital mortality of 4.5% (n=5). A total of 64 patients (81% men, 59±9 years old, 81% with epithelial histologic subtype) underwent induction chemotherapy, while 39 (82% men, 62±9 years old, 69% with epithelial histologic subtype) underwent SMART. Seven patients had no induction therapy and one had pre-operative chemo- and radiation therapy. Since 2008, the number of surgical patients undergoing SMART progressively increased from 14% in 2008 to 100% in 2013. None of the patients undergoing SMART died in hospital or within 30 days of surgery, while 4 of the 64 patients (6.4%) undergoing induction chemotherapy died in hospital after EPP (p=0.1). Patients undergoing SMART tended to have a greater proportion of ypN2 disease on final pathology than patients completing induction chemotherapy before EPP (58% vs 41%, respectively; p=0.09). After a median follow-up of 16 months after the start of therapy, the 3-year survival was significantly better in patients with epithelial disease undergoing SMART (n=27) compared to patients with epithelial disease undergoing induction chemotherapy and EPP (n=52) (79% 3-year survival vs 30% 3-year survival, respectively; p=0.04). In contrast, the 3-year survival of patients with biphasic disease was similar between patients undergoing SMART (n=12) or induction chemotherapy and EPP (n=12) (20% vs 8%, respectively; p=0.8). Multivariate survival analysis using Cox regression model demonstrated that epithelial histologic subtype (p=0.0003), the absence of ypN2 disease (p=0.007) and SMART (p=0.03) were predictors of better survival.

      Conclusion
      Over the past 5 years, accelerated hemithoracic IMRT followed by EPP has become our preferred approach for surgically resectable MPM. Surgery for mesothelioma after radiation therapy was feasible with no operative mortality in 39 patients. Although comparison with our historical cohort of patients has limitations, our current protocol provides very encouraging results in patients with epithelial disease with a 3 year survival of 79%.

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      MO14.12 - Neoadjuvant Hemithoracic Intensity Modulated Radiotherapy: The "SMART" Approach for Managing Malignant Pleural Mesothelioma (ID 2328)

      10:30 - 12:00  |  Author(s): A. Hope

      • Abstract
      • Presentation
      • Slides

      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.

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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: 3
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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)

      16:15 - 17:45  |  Author(s): A. Hope

      • Abstract
      • Presentation
      • Slides

      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 1

      Conclusion
      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.

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      MO17.05 - Recurrence, Survival, and Toxicity after Stereotactic Lung Radiotherapy (SBRT) for Central versus Peripheral Stage I Non-Small Cell Lung Cancer (NSCLC): Results from an International Collaborative Research Group (ID 3436)

      16:15 - 17:45  |  Author(s): A. Hope

      • Abstract
      • Presentation
      • Slides

      Background
      SBRT is an accepted safe and effective treatment modality for peripheral (P) stage I NSCLC tumors. Concern of excessive toxicity, however, limits its use for central (C) tumors. This study evaluates outcomes and toxicities after cone-beam CT (CBCT) image-guided SBRT for central vs. peripheral NSCLC.

      Methods
      959 lung tumors were treated with lung SBRT from 1998-2012 at five international centers participating in the Elekta Collaborative Lung Research Group; 98% underwent online CBCT IGRT. 100 cases were classified as Central (C) and 869 Peripheral (P), defined as ≤2cm vs. >2cm from the proximal bronchial tree, respectively. Staging included chest CT and routine chemistry for all; 93% had PET staging (mean time PET to SBRT 6.4 weeks); 6% had mediastinal sampling (mediastinoscopy or endobronchial ultrasound). 61% had tumor biopsy (84% C vs. 59% P, p<0.001). 89% were medically inoperable with mean baseline FEV1 of 1.6L (63% of predicted) and mean baseline DLCO of 12.1 ml/min/mmHg (56% of predicted). Mean age was 74y (42-93) with a large range in ECOG performance status (27%; 47%; 23%; 26% for 0-3, respectively). Clinical stage was T1aN0 44%, T1bN0 30%, T2aN0 23%, T2bN0 32%. Mean tumor maximum dimension was 2.5cm (range 0.5-8.5cm); C tumors were larger (mean 3.lcm vs. 2.4 cm, p<0.001). Mean SBRT prescription dose was 51.5±6.4 Gy, with mean dose per fraction of 14.5±4.0 Gy in 3.9±1.5 fractions. Mean biological equivalent dose (BED) was 126.6±26.6 Gy, higher for P vs. C tumors (129.2 vs. 104.0 Gy, p<0.001. Chemotherapy was administered more for C (9%) than P tumors (2%), p<0.001. Groups were compared with t-test & chi-square. Competing risks analyses were used, accounting for the competing risk of death.

      Results
      Mean follow-up for all cases was 1.8y (0.1-7.7y; mean potential follow-up 3.4y), similar for C&P. C tumors had higher Local Failure (LF) (3y-LF 16.2%C vs. 5.9%P; 5y-LF 20.4%C vs. 8.3%P, p<0.001), similar regional nodal recurrences (RR) (3y-RR 12%C vs.12%P, p=0.69) and distant metastases (DM) (3y-DM 19%C vs 20%P, p=0.75), lower cause-specific survival (CSS) (3yr-CSS 75%C vs. 88%P, p<0.001), but similar overall survival (OS) (3y-OS 50%C vs. 51%P, p=0.70). Grade > 2 pneumonitis was higher for C tumors (8%C vs. 1%P, p<0.001). Incidence of grade 3 pneumonitis, chest wall pain/myositis, rib fracture, and skin dermatitis were rare (0.8%, 0.5%, 0.4%, 0.6% respectively for all) with no differences between C&P. No grade 4 toxicities were noted, though 2 cases (1C & 1P) of fatal pneumonitis were potentially attributable to SBRT. On multivariate analysis, BED (HR:0.975, p<0.001) predicted CSS, and both BED (HR:0.978, p=0.002) and baseline SUVmax (HR:1.04, p=0.001) predicted LF. Weeks from PET-staging until SBRT (HR:1.25, p=0.004) and the percent of lungs receiving >20 Gy (HR:1.063, p=0.001) were the strongest independent predictors of OS.

      Conclusion
      In this large data set, pneumonitis was higher for central tumors, but both central & peripheral SBRT were safe with similar overall and cause-specific survival. LF was higher for central tumors, which were larger, had higher baseline SUVmax, and received lower dose. Results of the ongoing RTOG 0813 dose-finding study for central tumors are awaited.

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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)

      16:15 - 17:45  |  Author(s): A. Hope

      • Abstract
      • Presentation
      • Slides

      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 1

      Conclusion
      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.

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    O01 - Prognostic and Predictive Biomarkers I (ID 94)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 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 - 12:00  |  Author(s): A. Hope

      • Abstract
      • Presentation
      • Slides

      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).

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    O10 - Stereotactic Ablative Body Radiotherapy (ID 104)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 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)

      16:15 - 17:45  |  Author(s): A. Hope

      • Abstract
      • Presentation
      • Slides

      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

      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%
      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.

      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.

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    P1.08 - Poster Session 1 - Radiotherapy (ID 195)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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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 - 16:30  |  Author(s): A. Hope

      • 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: 1
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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 - 16:30  |  Author(s): A. Hope

      • 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.