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M. Putt



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    MO09 - Mesothelioma I (ID 120)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track:
    • Presentations: 2
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      MO09.12 - Posterior intercostal lymph nodes - First report of a new independent prognostic factor for malignant pleural mesothelioma (ID 1684)

      16:15 - 17:45  |  Author(s): M. Putt

      • Abstract
      • Presentation
      • Slides

      Background
      Little is known about the significance of metastases to the posterior intercostal lymph nodes, located within the intercostal spaces at the level of the rib heads, in patients with malignant pleural mesothelioma. These nodes are not part of any staging system. This report is an initial attempt to determine the significance of these lymph nodes.

      Methods
      We sampled posterior intercostal lymph nodes from 48 patients undergoing radical pleurectomy for malignant pleural mesothelioma. Statistical analyses were then performed correlating metastases to these lymph nodes with progression free and overall survival.

      Results
      26/48 (54%) patients had positive posterior intercostal lymph nodes. Standard staging revealed: 6/48 (13%) N0, 3/48 (6%) N1, 39/48 (81%) N2, 9/49 (19%) stage III and 39/48 (81%) stage IV. Presence of positive posterior intercostal lymph nodes was not associated with stage (Fisher exact P=0.48), but was associated with N status. N1 and N2 were associated with higher rates of positive posterior intercostal lymph nodes (Fisher exact P=0.011). At a median follow-up of 9.6 months, progression-free survival was 0.83 years, 95% CI: (0.74, 1.30) years; median overall survival was 1.89 years, 95% CI: (1.29, ND) years. Patients with negative posterior intercostal lymph nodes had a median progression-free survival of 1.25 years, 95% CI: (0.95, 1.95) years, while that for patients with positive posterior intercostal lymph nodes was 0.73 years, 95% CI: (0.61, 1.40) years (p=.017 by log-rank test). Patients with negative posterior intercostal lymph nodes had a median overall survival of 3.43 years, 95% CI: (1.89, ND) years, while that for patients with positive ICLNs was 1.01 years, 95% CI: (0.61, 1.40) years (p=.007 by log-rank). In a Cox regression model that adjusted for stage, positive posterior intercostal lymph nodes were associated with an increased risk of failure (HR=2.71, 95% CI=1.15.6.39, P=.048) and death, (HR=3.3, 95% CI: 1.3, 8.1, P=0.0098. Figure 1

      Conclusion
      Bearing in mind the limitations of this retrospective study with short-term follow-up, these results suggest that the posterior intercostal lymph nodes may have independent prognostic significance. This data has served as a trigger for us to now routinely include the posterior intercostal lymph nodes in our thoracic lymphadenectomies in patients undergoing surgery for malignant pleural mesothelioma. Further investigation of this nodal station is indicated and it is likely that these nodes should be included in any future staging system for malignant pleural mesothelioma.

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      MO09.13 - Comparison of Three Radiographic Tumor Volume Estimation Techniques for Malignant Pleural Mesothelioma: Their Correlation with Each Other, Actual Measured Intraoperative Tumor Volumes, and Survival (ID 1689)

      16:15 - 17:45  |  Author(s): M. Putt

      • Abstract
      • Presentation
      • Slides

      Background
      Studies have assessed correlation between radiographically estimated tumor volume (TV) and outcomes for malignant pleural mesothelioma, no standard radiographic model exists for estimating TV. Although radical pleurectomy yields a surgical specimen essentially all cancer, thereby allowing accurate determination of TV, empirically-derived intraoperative TVs have never been reported. We compare multiple radiographic estimates of TV with TVs determined at resection to determine which radiographic approach most accurately predicts intraoperative TV, and we correlate TV with survival.

      Methods
      Actual TVs were measured for 41 consecutive radical pleurectomy specimens by volume displacement. Radiographic TV estimates were performed by radiologists/radiation oncologists blinded to intraoperative TVs. Radiographic estimates were obtained with: Live Wire algorithm (automated tumor delineation after manual algorithm training), radiology TeraRecon (tumor automatically circumscribed with subsequent manual tracing corrections), and radiation oncology Eclipse (non-automated tumor delineation).

      Results
      Median age was 63yrs, with 80% male and 83% having epithelial histology. Stage distribution was: 3-Stage I (7%), 4-Stage II (10%), 29-Stage III (71%), and 5-Stage IV (12%). Median (interquartile range) intraoperative TV was 600(400,800)cm[3]. Median TV of 800(575,1100)cm[3] among nonepithelial compared to 500(350,838)cm[3] for epithelial was not significantly difference (p=0.099). TVs were largest for stage III (p=0.01). Median TVs for Live Wire, TerraRecon, and Eclipse were 260(147-452), 293(161-465), and 447(247-559)cm[3], respectively. Pearson correlation coefficients were 0.60, 0.75, and 0.78, with all models underestimating intraoperative TVs (Figure 1A). Among 34 epithelial patients (mean/median follow-up 9.8/8.0mo), median survival was not reached (only 9 recurrences). Epithelial patients with large (>500cm[3]) intraoperative TVs had numerically worse progression-free (p=0.148) and overall (p=0.161) survival than patients with TVs ≤500cm[3](Figure 1B), but limited events precluded statistical significance. Larger radiologic TVs similarly correlated with shorter survivals. Figure 1

      Conclusion
      This is the first study to compare radiographic estimates of TV to actual TV determined by volume displacement of radical pleurectomy specimens, arguably the TV measurement gold standard. This study is also the first to compare estimated TVs using multiple established and previously reported radiographic techniques. Our results demonstrate a clear trend toward greater overall and progression-free survival for actual TVs <500cm[3]. All radiographic techniques underestimated actual TV, with estimates progressively closer to the actual volume with each technique as they became less automated and more manual. Further analysis is ongoing to determine if any radiographic method can serve as an accurate surrogate for actual TV and if models correlate as closely with outcomes as actual TVs.

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

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 1
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      MO14.01 - The impact of macroscopic complete resection radical pleurectomy for mesothelioma on pulmonary function (ID 1692)

      10:30 - 12:00  |  Author(s): M. Putt

      • Abstract
      • Presentation
      • Slides

      Background
      Radical pleurectomy is our standard approach for achieving a macroscopic complete resection in patients with malignant pleural mesothelioma undergoing surgery-based treatment. This procedure, not pneumonectomy, is performed even in the setting of advanced stage disease, bulky tumors and/or extensive involvement of the pulmonary fissures. Although the majority of patients subjectively rate their breathing as “good” after this operation we recently started measuring postoperative pulmonary function, reported herein.

      Methods
      We examined pre and postoperative FEV~1~ levels among 27 patients undergoing radical pleurectomy: 2 stage I, 3 stage II, 17 stage III, 5 stage IV.

      Results
      The figure shows pre/postoperative FEV-1. Median preoperative levels did not differ significantly between stages (P=0.25): 2.47 (Stage I/II) 2.19 (Stage III) and 1.68 (Stage IV) liters/second. Post-operative median values were 2.16 (Stage I/II), 1.97 (Stage III) and 1.05 (Stage IV) liters/second. The median (interquartile range) decrease in FEV-1 was 0.28 (0.12, 0.51) liters/second, which corresponds to a median (interquartile range) decrease in percent predicted FEV-1 of 7% (4.5%, 16.0%), neither change being statistically significant between stages. Figure 1

      Conclusion
      These operations were conducted in an advanced stage cohort of patients, 81% stage III or IV. The nominal decrease in FEV1 corresponds with the subjective impression of the patients regarding their pulmonary function. While lung parenchyma is preserved with radical pleurectomy, we conjecture the decrease in FEV1 is likely related to compromise in breathing mechanics. Further studies are ongoing to better quantify and characterize the decrease in pulmonary function observed with this operation and to more rigorously integrate this information with formal quality of life assessments.

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