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Robert M. Macrae



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    OA06 - Early Stage Lung Cancer: Outcomes and Interventions (ID 902)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 202 BD
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      OA06.01 - Case-Series Study in Ever- and Never-Smoking Females and Males with NSCLC: Exposures, Tumor Factors, Biology and Survival (SWOG S0424) (ID 14526)

      13:30 - 13:40  |  Author(s): Robert M. Macrae

      • Abstract
      • Presentation
      • Slides

      Background
      Sex differences in non-small cell lung cancer (NSCLC) susceptibility, tumor biology and survival have been retrospectively reported. We conducted a prospective, case-series intergroup study (SWOG S0424) in 4 cohorts of females (F) and males (M), ever-smokers (ES) and never-smokers (NS) with newly-diagnosed stages I-III NSCLC. This is the first overall survival (OS) report. a9ded1e5ce5d75814730bb4caaf49419 Method
      Patients were accrued at US sites via SWOG/NCI-CTSU. A questionnaire of demographics and exposures (tobacco, environmental, reproductive, hormonal); stage and histology data; treatment; and OS were obtained. Tumor tissue was submitted for EGFR, RAS and p53 mutations. Nuclear and cytoplasmic estrogen receptor (ER) alpha and beta were measured (Cheng, JNCI 2017). Kaplan-Meier (KM) curves and OS modeled using Cox proportional hazards were examined. The NS cohorts remained open longer to maximize accrual. Patients were followed 5 years for OS or until death. 4c3880bb027f159e801041b1021e88e8 Result
      The accrual goal of 981 was achieved from 10/2005-3/2011. Evaluable cases were FES, n=337; MES, 383; FNS, 188; MNS, 49 (MNS under-accrued despite extension). The 4 cohorts differed significantly in demographics, tumor stage, histology, mutational profile (overall, by histology), ER expression, lifestyle factors and exposures. KM curves showed MNS/MES had overlapping OS and FNS/FES had significantly better OS. Five-year estimates were FNS, 73%; FES, 69%; MNS, 58%; MES, 52%. Markedly improved OS for females persisted after adjusting for other factors. Four multivariate OS models were constructed: all patients (model 1) and women only (model 2), each with mutations and ER expression added (models 3, 4). Model 1: better OS for females (HR 0.56, p <.001); higher BMI (continuous, HR 0.98, p=0.045); and adenocarcinoma, BAC, large cell (all vs squamous, HRs 0.84, 0.48, 0.57); worse OS for stages II and III (HRs 1.87, 3.76: each p<.001) and greater age. Model 2: worse OS if ES (HR 1.48, p=0.05), higher stages; histology and hormonal exposure variables were not significant. Model 3: better OS if EGFR mutation (HR 0.53, p=0.013), female, stage I, higher BMI or greater height; worse OS if p53 mutation, higher ER-alpha cytoplasmic or ER-beta nuclear H-scores. Model 4: worse OS if higher stage, p53 mutation or ER-alpha cytoplasmic H-score; EGFR mutation lost significance. 8eea62084ca7e541d918e823422bd82e Conclusion
      Sex, histology, mutations and exposures impacted OS, with dramatically better OS for females regardless of the analysis/model. Hormonal influences (persistent association of ER-expression with OS) were independently significant. Despite adjustments, favorable female survival could not be explained away. Randomized studies should stratify by sex and validation analyses should be conducted in targeted therapy and immunotherapy trials.

      SUPPORT: NIH/NCI grants R01CA106815, U10CA180888, U10CA180819 and UG1CA189974. 6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 965)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.16-19 - Feasibility and Outcomes of Radiofrequency Ablation as Salvage Modality After Hypofractionated Radiation/SBRT for Early NSCLC (ID 12614)

      16:45 - 18:00  |  Author(s): Robert M. Macrae

      • Abstract
      • Slides

      Background

      Local recurrences after radiotherapy (RT) for early non-small cell lung cancers (NSCLC) may be amenable to curative treatments. One such modality is Radio Frequency Ablation (RFA). There is paucity of data about outcomes after RFA salvage. We aim to evaluate the feasibility and outcomes of RFA when used as salvage therapy after hypo-fractionated radiation for early NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed consecutive early NSCLC patients treated with SBRT or hypo-fractionated radiation followed by RFA salvage in an ethics board approved study. RFAs were performed using CT guidance and under general anesthesia using LeVeenTM needle. Its immediate and follow up complications were assessed. The end points of interest were local recurrence free survival (LRFS), distant relapse free survival (DRFS) and overall survival (OS). The end points were compared by the tumour size and Positron Emission Tomography (PET) maximum Standardized Uptake Value (SUVmax)

      4c3880bb027f159e801041b1021e88e8 Result

      20 individuals with 21 tumours were treated with salvage RFA after RT for early tumours between 2005 and 2017. The median age was 76 years(52-94). Initial treatment was SBRT in 55%(11/20) tumours. 55%(11) tumours were adenocarcinomas, 25%(5) were squamous and 20%(4) were NSCLC- not otherwise specified. The median tumour size (long axis diameter) was 31.5mms. PET was available for 16 tumours and the median SUVmax was 6.15. The median interval since prior radiation was 24 months(8-56). The procedure was well tolerated. One individual developed pneumothorax requiring pigtail catheter drainage. The median hospitalization period was 1 day. One procedure was aborted midway due to lancinating ipsilateral arm pain. Two patients required 3 and 5 days of hospitalization respectively because of post-procedural pain.​ Chronically, one individual developed tissue necrosis syndrome, one individual developed hydropneumothorax and one individual developed dysphonia. The median LRFS was 31.8 months. When stratified by ≤ or >30 mms, there was no statistically significant difference in mean LRFS, but a trend was noted. Onset of distant metastases was slightly earlier in larger tumors but not statistically significant. The median overall survival for tumours ≤ or >30 mms was 42.8 months and 17.4 months respectively (p-0.015). THE LRFS was 27.7 and 60.45 months (p-0.29), DMFS was 27.8 and 54.7 months (p-0.11) for patients with PET SUV >5 and ≤5 respectively .

      8eea62084ca7e541d918e823422bd82e Conclusion

      RFA is an effective and feasible salvage modality in early NSCLC after radiation. This study is limited by its retrospective nature and limited numbers. A larger prospective analysis will help ascertain its role.

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    SH01 - Highlight of the Previous Day Sessions (ID 884)

    • Event: WCLC 2018
    • Type: Highlight of the Day Session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 07:00 - 08:00, Plenary Hall
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      SH01.01 - Advances in Radiation (ID 13421)

      07:12 - 07:24  |  Presenting Author(s): Robert M. Macrae

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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