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D.A. Palma



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    OA 16 - Treatment Strategies and Follow Up (ID 686)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Early Stage NSCLC
    • Presentations: 1
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      OA 16.01 - Stereotactic Ablative Radiotherapy Versus Surgery in Early Lung Cancer: A Meta-analysis of Propensity Score-Adjusted Studies (ID 8066)

      14:30 - 16:15  |  Author(s): D.A. Palma

      • Abstract
      • Presentation
      • Slides

      Background:
      There is currently no completed randomized controlled trial data comparing stereotactic ablative radiotherapy (SABR) and surgery in operable patients with early-stage non-small cell lung cancer (ES-NSCLC). Propensity score methods are increasingly utilized in oncology to balance the baseline characteristics of non-randomized cohorts, mimicking the setting of a clinical trial. No previous meta-analysis of propensity score analyses comparing a surgical and non-surgical modality has been conducted. Our goal was therefore to perform a systematic review and meta-analysis of all propensity score analyses comparing SABR and surgery in patients with ES-NSCLC.

      Method:
      A systematic review was carried out according to PRISMA guidelines by querying the MEDLINE and Embase databases from inception until December 2016. Hazard ratios (HR) with confidence intervals (CI) for overall survival (OS) and disease-specific survival (DSS) were directly extracted, if available, or estimated from Kaplan-Meier curves. Meta-analysis was carried out with inverse variance-weighted random-effects models.

      Result:
      After reviewing 1039 records, 17 PS-adjusted studies with a total of 20151 patients were included in the final analysis. Overall survival (OS) favoured surgery over SABR (HR = 1.52 [95% CI: 1.33-1.74], p < 0.001). However, the rate at which patients died from lung cancer (DSS) was not significantly different (HR = 1.13 [95% CI: 0.86-1.49], p = 0.38). On subgroup analysis, OS was superior for both lobectomy (HR = 1.61 [95% CI: 1.27-2.03], p < 0.001) and sublobar resection (HR = 1.33 [95% CI: 1.15-1.55], p < 0.001) versus SABR while DSS again did not significantly differ (HR = 1.35 [95% CI: 0.70-2.62] and HR = 1.18 [95% CI: 0.84-1.67], respectively). On secondary analysis, meta-analysis of proportions revealed a lymph node upstaging rate of 16.0% (95% CI: 13.6%-18.6%) and adjuvant chemotherapy usage rate of 11.5% (95% CI: 8.6%-14.8%) among patients who received surgery. On meta-regression, with every increase of 0.1 in the maximum allowable difference in propensity score within a matched pair - representing increases in imbalance between cohorts, DSS outcomes increasingly favoured surgery by 1.36-fold. Critical appraisal revealed inconsistent reporting of propensity score methods.

      Conclusion:
      Overall survival favoured surgery over SABR in this meta-analysis of 17 propensity score analyses. However, the effectiveness of SABR was reflected in a similar DSS to surgery, supporting ongoing clinical equipoise. A direct relationship between propensity score methodology and DSS outcomes were demonstrated. Whether this observed benefit in OS for surgery is real or due to limitations in the propensity score methodology requires confirmation through randomized data.

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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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      P1.14-018a - Stereotactic Ablative Radiotherapy for Ultra-Central Lung Tumors: Optimize Tumor Control or Minimize Toxicity? (ID 9509)

      09:30 - 16:00  |  Author(s): D.A. Palma

      • Abstract

      Background:
      Lung stereotactic ablative radiotherapy (SABR) is associated with low morbidity, however there is an increased risk of treatment-related toxicity in tumors directly abutting or invading the proximal bronchial tree, termed ‘ultra-central’ tumors. For such tumors, there is no consensus regarding the most appropriate dose-fractionation scheme. The purpose of this planning study was to evaluate the therapeutic ratio of SABR treatment plans for ultra-central tumours using commonly utilized dose fractionation regimens.

      Method:
      In this research ethics board approved study, 10 patients with ultra-central lung tumors were identified from our institutional database. New plans were generated for each of the 10 cases using 3 different hypofractionated schedules: 50 Gy in 5 fractions, 60 Gy in 8 fractions and 60 Gy in 15 fractions. For each of the three dose regimens, 2 plans were generated, one prioritizing tumor coverage and the other plan compromising PTV coverage in order to respect the dose constraints for the esophagus, lung and proximal bronchial tree. Using published normal tissue complication probability models, plans were evaluated for likelihood of toxicity to these organs at risk.

      Result:
      In the scenario where PTV coverage was prioritized, the probabilities of acute esophageal or pulmonary toxicity were low, ranging from 0.9-1.2% and 3.7-4.3%, respectively. In contrast, the estimated risk of grade 4 or 5 toxicity to the proximal bronchial tree varied significantly: 68% for 50 Gy in 5 fractions, 44% for 60 Gy in 8 fractions and 2% for 60 Gy in 15 fractions. When dose to the organs at risk was prioritized, risk of toxicity to the proximal bronchial tree was reduced to <1% for all 3 dose fractionation schemes. This compromise resulted in a reduction in the calculated tumor control probabilities, from 92.9% to 60.3% for 50 Gy in 5 fractions, 92.4% to 65.7% for 60 Gy in 8 fractions and 52% to 47.8% for 60 Gy in 15 fractions.

      Conclusion:
      With the use of SABR or hypofractionated radiotherapy for ultra-central lung tumors, the competing risks of tumor local control and treatment toxicities need to be considered. Predicted rates of local control are inversely related to the risk of severe pulmonary toxicity due to trade-offs in the radiation planning process. Further prospective research is needed to better assess the optimal dose fractionation schedule for ultra-central lung tumors.

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    P2.14 - Radiotherapy (ID 715)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiotherapy
    • Presentations: 1
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      P2.14-009 - Assessing the Value of Radiotherapy for Lung Cancer in the Intensive Care Unit – A Population-based analysis (ID 9132)

      09:30 - 16:00  |  Author(s): D.A. Palma

      • Abstract

      Background:
      As the use of radiotherapy (RT) in lung cancer patients in the ICU is poorly described; we evaluated characteristics, outcomes, RT utilization and costs in a population-based cohort of ICU lung cancer patients in Ontario, Canada.

      Method:
      Eligible patients between April 1, 2007 and March 31, 2014 were identified through provincial administrative healthcare databases. Given that a patient could receive multiple RT deliveries, each ICU stay was analyzed separately as an episode of care. Significant differences in patient, treatment, institution and tumor characteristics between RT and non-RT groups were compared with t-tests and chi-square tests, as appropriate. Pre-ICU disposition was by ER admission, same institution admission or different institution transfer. The Kaplan-Meier method was used to estimate overall survival (OS), measured from index ICU admission to death, censoring at the end of the observation period. Differences in OS between the RT and non-RT groups were compared using the log-rank test. Univariable and multivariable Cox proportional hazard modeling were performed to assess the effect of RT on OS. Daily costs were calculated in 2015 Canadian dollars (converted using consumer price indices) for RT patients only, based on acute hospitalizations, ER visits, cancer clinic visits, same-day surgeries, and physician billings. For all analyses, a p-value threshold of <0.05 was used to define statistical significance.

      Result:
      In 13,739 unique lung cancer ICU patients, RT was delivered in 133 episodes to 1.0% (n=131) of patients. The RT group tended to be younger (median age 65 vs. 68, p<0.001), on some form of ventilation (79.8% vs. 38.2%, p<0.001) and with longer ventilation durations ((median [IQR]) 6 [1-11] vs. 0 [0-2] days, p<0.001). RT patients were more likely to present from the ER (28.2% vs. 21.9%, p=0.002) or via transfer (35.3% vs. 9.7%, p<0.001). While ICU discharge was common in both RT (56.4%) and non-RT (71.4%) cohorts, 1-year OS was poor with both groups, but most notably in the RT group (11.3% vs. 42.4%). RT was associated with inferior 1-year OS on unadjusted modeling (HR=1.99, 95% CI:1.65-2.38, p<0.001), with ventilation status and pre-ICU disposition adjusting this finding towards the null on multivariable modeling (HR=1.17, 95% CI:0.97-1.40, p=0.095). The median daily cost of medical care in RT patients was $2771 (IQR $1757-$3753), with acute hospitalization accounting for more than half (median $1723) of calculated costs.

      Conclusion:
      The use of RT needs to be considered judiciously for lung cancer patients in the ICU, given the poor prognosis and increased costs incurred.