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A.J. Hope



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    MA 09 - The Current Status of Radiation Oncology (ID 666)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      MA 09.02 - Ultra-Central Tumours Treated with Stereotactic Body Radiotherapy: A Single Institutional Experience (ID 8758)

      11:00 - 12:30  |  Author(s): A.J. Hope

      • Abstract
      • Presentation
      • Slides

      Background:
      Stereotactic body radiotherapy of “ultra-central” (UC) lung tumours, PTV directly abuts/overlaps the proximal bronchial tree (PBT), trachea, esophagus, pulmonary vein/artery, are considered to be at higher risk of toxicity. The purpose of this study is to review the outcomes and toxicities of Ultra-central lung tumours, compared to central tumours.

      Method:
      A retrospective review based on a prospective database of patients treated with lung SBRT from January 2006- December 2015 was conducted. Patients with central tumours defined using RTOG 0813 criteria and ultracentral tumours were included. 115 patients (53%) received 60Gy/8 and 61 (28%) received 48Gy/4. At our institution, the recommended Dmax for esophagus is 45Gy and 40Gy for 8 and 4 fractions, respectively. The Dmax and D10cc constraints for trachea, proximal bronchial tree, heart, and major vessels (including pulmonary artery and vein) are 48Gy and 40Gy for 4 fractions and 64 and 60Gy for 8 fractions. Toxicity was graded using CTCAE v3.0. Log-rank test was used to compare overall and cause-specific survival. Local, regional, and distant recurrence were compared using Gray’s test.

      Result:
      215 tumours were analyzed (189 C and 26 UC). The median age for C and UC were 75 years and 72.5 years. Median tumour size and PTV volume were 2.2 cm (range 0.9-5.7) and 41.7 cm3 (range 9.7-246.3) (C group) and 2.5 cm (0.8-5.5) and 58.2 cm3 (16.8-238.3) (UC group). The percentage of squamous cell carcinoma was higher in the UC group (15%, n=29 in C; 38%, n=10 in UC). The median follow-up was 20.3 months (24.5 mo for patients still alive). Median overall survival (OS) and cause-specific survival (CSS) was 34 mo and 53.8 mo for C and 20.1 mo and 28.2 mo for UC, respectively. Differences in OS and CSS between the two groups did not meet statistical significance (p=0.24 and p=0.14, respectively). Local, regional, and distant failure rates were 3%, 8% and 18% in the central tumour group and 0%, 9% and 25% in the ultra-central tumour group at 2 years. There was no statistically significant difference found in the rates of recurrence between the two groups. The rates of any grade 2 or higher toxicity (hemoptysis, esophageal toxicity, cough, dyspnea, pneumonitis) was 9% (n=17) in the C and 7.7% (n=2) in UC group (p=0.89). There were no known grade 4 or 5 toxicities.

      Conclusion:
      In our experience, SBRT to ultra-central tumours resulted in effective local control and no excessive risk of toxicity compared to central tumours.

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    MA 13 - New Insights of Diagnosis and Update of Treatment (ID 674)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Early Stage NSCLC
    • Presentations: 1
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      MA 13.09 - Toxicity and Second Primary Lung Cancers in Late Survivors Following Lung SBRT (ID 8410)

      15:45 - 17:30  |  Author(s): A.J. Hope

      • Abstract
      • Presentation
      • Slides

      Background:
      There is a paucity of data on the long-term outcomes following lung SBRT. This impacts our understanding of late toxicity, relapse patterns and rates of second lung cancers. We report our multi-institutional outcomes of those who survived ≥5 years from lung SBRT treatment.

      Method:
      1192 patients were treated for primary non-small cell lung cancer, T1/2N0 from 5 international institutions. For those who survived ≥5 years from lung SBRT treatment details of patient factors, treatment and outcome factors were extracted from the multi-institutional database. All events were calculated from the end of radiotherapy. Local (LR), regional (RR), and distant metastases (DM) and toxicity events after 5 years are reported. New cases of metachronous lung cancers after 5 years are reported. Univariable analyses was performed to determine factors associated with survival ≥5 years.

      Result:
      Of 1192 patients there were 182 (14%) ≥5 year survivors. Only 52 (8%) survived ≥ 7 years and 2 (0.2%) ≥10 years. Those surviving ≥5 years were younger (74.3 vs 71.5 years; p<0.01) and had better FEV1 (55% vs 65%; p<0.01) than those that did not survive 5 years. The Charleston Comorbidity Score was 1.4 (0-12) vs 2.1 (0-7) (p<0.001) in those who survived < vs ≥5 years. Those who survived <5 years had a trend to larger tumors (2.4cm vs 2.3 cm; p=0.07). Of the 182 patients 23 (13%) were operable, 67 (37%) were <70 years old at treatment, 115 (63%) were ECOG 0-1 and 156 (86%) had peripheral tumor location at time of initial diagnosis. 84 (46.2%) were T1a, 60 (33%) T1b, 33 (18.1%) T2a and 5 (2.7%) T2b. After 5 years there were 13 new events of grade ≥ 2 toxicity. These toxicities were 4 grade 2 fatigue, 1 grade 2 rib fracture, 7 grade 2 chronic myositis and 1 patient with grade 2 chronic myositis and fatigue. In this 182 patient cohort, after 5 years, there were 3 local recurrences, 2 regional failures and 5 distant failures. After 5 years follow-up there were 22 (12%) new primary lung tumors in the 182 patients (and 20 had a subsequent lung SBRT treatment).

      Conclusion:
      Late survivors after SBRT require dedicated follow-up as they remain at risk for second lung cancer, tumor recurrence and toxicity. Second cancers in these late survivors can be considered for SBRT treatments.

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    MA 16 - Mediastinal, Tracheal and Esophageal Tumor: Multimodality Approaches (ID 675)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      MA 16.03 - Health Utility Scores in Patients with Thymic Malignancies Treated with Multimodality Therapy (ID 9651)

      15:45 - 17:30  |  Author(s): A.J. Hope

      • Abstract
      • Presentation
      • Slides

      Background:
      The management of patients with locally advanced thymic malignancies remains controversial. Various combinations of surgical resection, chemotherapy and radiation are currently used. Given the generally favorable prognosis, treatment related toxicities and quality of life (QOL) could inform therapeutic options. For economic analyses, QOL can be measured as health utilities. This study describes health utility scores (HUS) in patients with locally advanced thymic malignancies, while determining the impact of multimodality regimens on HUS.

      Method:
      In a cross-sectional study (2014-2017), patients with Masaoka stage II-IVa thymic malignancies seen at a comprehensive cancer centre completed various self-reported questionnaires at routine medical visits. HUS as measured by the EuroQol-5-Dimensions (EQ-5D) with visual analogue scale (VAS) and self-reported Eastern Cooperative Oncology Group (ECOG) performance status were compared in patients treated with trimodality versus uni- or bimodality regimens. Patient-reported Edmonton Symptom Assessment Scale (ESAS) scores were also collected to explore symptom burden. Regression analysis was used to compare groups; multivariable analysis investigating potential confounders was also conducted.

      Result:
      From 2014 to 2017, 72 patients were included in the study; 43 (59.7%) were male with a median age of 58 years, 65 (90.3%) had thymoma while 7 (9.7%) had thymic carcinomas and median time since diagnosis was 50.5 months (range: 3-266). Compared to patients treated with uni/bimodality regimens (n=48), those treated with trimodality (n=24) had higher stage of disease at diagnosis and were more likely to have received multiple lines of chemotherapy. Median HUS and VAS did not differ between groups (trimodality vs uni/bimodality: HUS=0.77 vs 0.80, p=0.26; and VAS=80 vs 75, p=0.79, respectively). The distribution of patient-reported ECOG at assessment was also similar (p=1.00). ESAS scores for pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing and shortness of breath were neither statistically nor clinically different by number of modalities of therapy. Subset analyses of individuals who were 1+ year since diagnosis affirmed these findings.

      Conclusion:
      Patients with stage II-IVa thymic malignancies report favorable HUS, VAS and self-reported ECOG with minimal symptom burden. Trimodality therapy appears similarly tolerable when compared to uni- and bimodality regimens in this population.

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    P1.13 - Radiology/Staging/Screening (ID 699)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P1.13-004 - The Role of Lymph Node Staging by EBUS-TBNA in Stereotactic Body Radiation Therapy for patients with Non-Small Cell Lung Cancer. (ID 8070)

      09:30 - 16:00  |  Author(s): A.J. Hope

      • Abstract
      • Slides

      Background:
      Stereotactic body radiation therapy (SBRT) is an option for treatment of patients with non-small cell lung cancer (NSCLC). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive, diagnostic modality for mediastinal and hilar staging of NSCLC. We evaluated the diagnostic value of EBUS-TBNA in SBRT candidates and compared it to that of computed tomography (CT) and positron emission tomography (PET) scans.

      Method:
      Inclusion criteria for this single institutional retrospective study included 1) biopsy-proven or clinically suspicious NSCLC with diameter <6 cm; 2) no evidence of distant metastasis; 3) EBUS-TBNA staging between April 2008 and November 2014; 4) medically SBRT-eligible other than nodal staging. CT and PET positive nodes were defined as short axis ≧1cm and standardized uptake value ≧2.5, respectively. Node positive by clinical-pathologic confirmation (NPCP) was defined as confirmed malignancy by EBUS-TBNA or clinically diagnosed recurrence in hilar or mediastinal lymph nodes within one year after SBRT. The survival after SBRT was compared between CT or PET node-positive but EBUS-TBNA result-negative patients, and a matched cohort (tumor size; radiation dose; operability) who underwent SBRT in our institution within the same time period but without EBUS-TBNA staging.

      Result:
      There were 35 eligible patients (mean age 77±8.2, 24 male). Thirty-two (91.4%) patients had pathological confirmation of NSCLC (mean diameter 2.5±1.0 cm) (T1a N=12, T1b N=15, T2a N=7, T2b N=1). Thirty (85.7%) patients were medically inoperable. After EBUS-TBNA, 20 out of 24 patients who had positive nodes in CT (N=13) or PET (N=17) were ultimately pathologically N0. All eleven image-negative patients were N0 following EBUS-TBNA. Thirty-one patients (20 image positive plus 11 image negative) underwent SBRT. Sensitivity/specificity of CT, PET and EBUS-TBNA for NPCP were 42.9/64.3%, 100/64.3% and 57.1/100%, respectively. Positive predictive value of CT and PET for NPCP was 23.1% and 41.2%, respectively. Negative predictive value of CT, PET and EBUS for NPCP was 81.8%, 100% and 90.3%, respectively. A 1:4 (Case; N=20, Control; N=76) match was obtained. Regional failure-free survival (p=0.71, HR=0.88 CI 0.45-1.74) and disease-free survival (p=0.77, HR=1.10 CI 0.58-2.11) of the Case were not significantly different from the ones of Control. There were no major complications related to EBUS procedures.

      Conclusion:
      EBUS-TBNA can be considered for invasive staging in SBRT-eligible NSCLC patients with radiographically positive lymph nodes because of its safety and possibility of false positive imaging. If EBUS-TBNA result is negative, these patients may remain candidates for SBRT with comparable outcomes to those who are conventionally selected for SBRT.

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    P1.14 - Radiotherapy (ID 700)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiotherapy
    • Presentations: 1
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      P1.14-016 - Assessing the Feasibility of FLT-PET for Evaluation of Non-Small Cell Lung Cancer (NSCLC) Treated with Stereotactic Body Radiotherapy (SBRT) (ID 8455)

      09:30 - 16:00  |  Author(s): A.J. Hope

      • Abstract

      Background:
      Distinguishing fibrosis from tumor recurrence following lung SBRT remains a clinical challenge since CT has poor sensitivity and specificity for detecting recurrence. 18F-Fluoro-L-thymidine-PET (FLT-PET) uptake correlates with cell proliferation. The purpose of this study is to investigate the feasibility of FLT-PET as an imaging biomarker for lung SBRT response assessment.

      Method:
      In this prospective study, three groups were included: 1) newly-diagnosed biopsy-proven NSCLC pre-SBRT, 2) established post-SBRT mass-like fibrosis on serial follow-up CT scans by co-investigators’ consensus, and 3) biopsy-proven locally-recurrent NSCLC after SBRT. Non-gated, helical gated (3D-CT/4D-PET) and phase-matched (4D-CT/4D-PET) FLT-PET images were obtained. Group-1 underwent fluorodeoxyglucose (FDG)-PET scan according to clinical guidelines. FLT uptake was measured by SUV95 and SUV50 (95% and 50% of maximum pixel value plus average background value, respectively), SUV2Dpeak and SUV3Dpeak (1cm diameter circular or spherical around region of interest, respectively), SUVmean and SUVmax. Descriptive statistics were gathered. Kolmogorov–Smirnov test was used to determine normality. Statistical significance was reported using student’s t-test.

      Result:
      27 patients were included, with 19 primary tumors (group-1), 12 established fibrosis (group-2) and 1 recurrence (group-3). In group-1, 16 tumors were T1. Group-1, mean FDG-PET SUVmax, SUV95, SUV50, SUV2Dpeak, SUV3Dpeak and SUVmean were 7.40, 5.88, 2.39, 5.59, 6.02 and 2.78, respectively. Mean FLT-PET values for group-1 were 3.43, 2.84, 1.71, 2.9, 2.82 and 1.78, respectively. Group-2 SBRT dose was either 48Gy in 4 fractions (83%) or 60Gy in 8 fractions. Median time from radiation to FLT-PET scan in group-2 was 19.5 months (5.8-83.8mos). The patient in group-3 had SUV50, SUV95, SUV2Dpeak, SUV3Dpeak, SUVmean and SUVmax of 2.27, 3.85, 6.37, 6.05, 2.39 and 7.64, respectively. Mean FLT-PET SUVmax for groups 1 and 2 was significantly different (p=0.03) at 3.42(1.14-7.04) and 2.34(1.23-4.35) respectively. Similarly, mean (range) of SUV50, SUV95 and SUVmean for group-1 was 1.8(0.74-3.43), 2.97(1.03-5.83), 1.87(0.73-3.44), and for group-2 was 1.22(0.81-2.26), 1.85(1.13-3.8) and 1.25(0.83-2.39), respectively (p<0.01, <0.01 and <0.01). There was no statistically-significant difference between SUV2Dpeak and SUV3Dpeak between groups 1 and 2, with a mean of 2.97(0.99-6.30) and 2.91(0.90-6.11) for group-1 and 2.10(1.11-3.91) and 2.03(1.00-3.86) for group-2 (p=0.06 and 0.06), respectively. There was no statistically significant difference between the 3D and 4D image acquisition in group-1. There were no FLT-PET-related toxicities.

      Conclusion:
      FLT-PET is feasible in SBRT patients pre- and post-treatment, and may assist in distinguishing fibrosis from recurrent tumor. Further validation studies are needed.

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    P3.09 - Mesothelioma (ID 725)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Mesothelioma
    • Presentations: 1
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      P3.09-007 - Thoracic Asymmetry and Its Impact on Survival after Radiation and Surgery for Malignant Pleural Mesothelioma (ID 9086)

      09:30 - 16:00  |  Author(s): A.J. Hope

      • Abstract
      • Slides

      Background:
      Staging for malignant pleural mesothelioma (MPM) remains a challenge due to poor prognostic utility. Other clinical factors may improve and refine the staging system. We investigate the impact thoracic asymmetry at time of initial presentation prior to therapy on survival in MPM patients treated with multimodal therapy.

      Method:
      We reviewed 93 consecutive treatment naïve MPM patients treated with Surgery for Mesothelioma after Radiation Therapy (SMART protocol) from Sep 2008 to Jul 2015. The right and left axial thoracic areas (defined as the product of the ant-post and med-lat extent of hemithoraces at the level of carina) were used to calculate the asymmetric thoracic ratio (ATR, where 1 is more symmetric, Figure 1). Significant factors were determined using univariate (log rank), multivariate (Cox proportional hazards) as well as recursive partition analysis (RPA). Continuous variables were discretized into binary categories split by its median value.

      Result:
      After a median follow-up of 15.6 months, 63 (68%) patients recurred, 56 (60%) died. The median ATR was 0.85, ranging from 0.52 to 1.00. On univariate analysis, histology (p=0.003 and 0.0002), gross tumour volume (GTV, p=0.004 and 0.001), and ATR (p=0.00001 and 0.0000002) all significantly impacted both overall and disease free survival, respectively, while mediastinal nodal involvement (p=0.03) was significantly associated with DFS only. On multivariate analysis, histology (p=0.01 and 0.005) and GTV (p=0.02 and 0.016) significantly impacted both overall and disease free survival, respectively. ATR significantly impacted disease free survival (p=0.02, HR=0.06 95% CI 0.02-0.20) and was suggestive of a trend for overall survival (p=0.07). On RPA, ATR<0.848 was significantly (p<0.001) associated with poorer DFS.

      Conclusion:
      A low asymmetric ratio (ATR<0.848) is significantly associated with poorer outcomes, specifically disease free survival, and is independent of histology and tumor volume. Further study is needed to validate this parameter.

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