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C. Simone



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    MO09 - Mesothelioma I (ID 120)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track:
    • Presentations: 1
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      MO09.12 - Posterior intercostal lymph nodes - First report of a new independent prognostic factor for malignant pleural mesothelioma (ID 1684)

      17:20 - 17:25  |  Author(s): C. Simone

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

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 2
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      MO14.01 - The impact of macroscopic complete resection radical pleurectomy for mesothelioma on pulmonary function (ID 1692)

      10:30 - 10:35  |  Author(s): C. Simone

      • 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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      MO14.02 - 16 Year Experience of Routine Laparoscopy and Selective Contralateral Thoracoscopic Staging for Malignant Pleural Mesothelioma (ID 1651)

      10:35 - 10:40  |  Author(s): C. Simone

      • Abstract
      • Presentation
      • Slides

      Background
      Surgery for malignant pleural mesothelioma (MPM) is typically restricted to patients without intraperitoneal or contralateral pleural spread. Imaging studies are accompanied by both false positive and false negative errors for both types of spread. To avoid these errors our group has routinely performed laparoscopy and selective contralateral video-assisted thoracoscopy (VATS) since 1997.

      Methods
      168 patients with MPM were evaluated for surgery as part of a multimodal treatment protocol. Radiographic staging studies included CT Chest with contrast for all 168 patients, PET Scan (112 patients) and MRI Abdomen (17 patients) for concerning findings on CT and/or PET. 150 patients underwent laparoscopy (two 5mm ports) with both peritoneal biopsy and lavage for cytology. 130/150 laparoscopies were performed in virgin abdomens with the remainder being reoperative procedures. 18 patients also underwent contralateral VATS, based upon any suspicious radiographic findings by either the interpreting radiologist or as reviewed by a multidisciplinary panel of treating physicians. All VATS were performed through a single 1 cm incision. Laparoscopies were performed as outpatient procedures. Patients undergoing combination VATS/laparoscopy were scheduled as same day admissions.

      Results
      There were no operative complications for either procedure. 5/132 (4%) laparoscopy patients scheduled as outpatients required overnight hospitalization – the most common reason being urinary retention. Laparoscopy revealed inaccuracies in radiographic staging in 13/150 (9%) patients- 6 false positive studies (1 interpretation of diaphragm transgression that was not through the diaphragm and 5 metastases that were not present) and 7 false negative studies (3 detected by lavage and 4 by biopsy). All of the false positive and all of the false negative studies occurred in patients who had PET scans. 2/18 (11%) patients who underwent VATS were positive for mesothelioma in the contralateral pleura, only one of whom had a positive PET scan finding.

      Conclusion
      Routine laparoscopy was performed safely and revealed inaccuracy in radiographic staging in 9% of the patients, all of whom had both CT and PET scans. Selective contralateral VATS was performed safely and revealed cancer in 11% of patients with suspicious findings, as determined by the interpreting radiologists and/or the treating clinicians and with PET only being accurate in one of the two positive findings. We conclude that prior to offering patients surgery-based treatment for MPM routine laparoscopy and VATS, based upon any suspicion, are indicated.

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    P1.14 - Poster Session 1 - Mesothelioma (ID 194)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Mesothelioma
    • Presentations: 1
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      P1.14-004 - Extended Survival Following Recurrence for Patients with Malignant Pleural Mesothelioma Treated with Radical Pleurectomy, Photodynamic Therapy and Chemotherapy: The potential role of STAT3. (ID 1686)

      09:30 - 09:30  |  Author(s): C. Simone

      • Abstract

      Background
      Survival after recurrence following surgical management with curative intent for malignant pleural mesothelioma is typically measured in months. In this study, we compare survival after recurrence in patients progression free less than or greater than one year after radical pleurectomy.

      Methods
      67 consecutive patients with malignant pleural mesothelioma, epithelial subtype, who underwent radical pleurectomy and intraoperative photodynamic therapy were assessed in this IRB-approved study. Four patients who experienced perioperative mortality were excluded from this analysis. Local recurrence was defined as recurrent disease in the ipsilateral hemithorax. Early vs. late recurrence was defined as recurrence before versus after the median recurrence time, respectively. STAT3 expression was quantified in tissue microarrays using computer-based quantification of immunohistochemical staining.

      Results
      Among the 63 evaluable patients, 78% (n=49) were male, the median age of patients was 64 years, and the overwhelming majority (87.5%) had locally advanced (AJCC stage3/4) disease. 49 patients (78%) had lymph node metastases (N1/N2). 60 patients (95%) received neoadjuvant or adjuvant pemetrexed-based chemotherapy. With a median follow-up of 31 months, 42 patients demonstrated disease recurrence. Of these recurrences, 18 were isolated local recurrences and 24 were combined local + distant. The median time to recurrence was 11.6 months and patients who experienced an early recurrence (<11.6 mo) demonstrated significantly decreased survival as compared to patients experiencing a late recurrence (p < 0.0001, Figure 1). The median survival after recurrence was significantly decreased for patients who experienced an early vs late recurrence (54.7 mo [46.0-63.4 mo 95% CI] vs 10.8 mo [8.5-22.7 mo 95 % CI], respectively). We and others have previously shown that STAT3 expression can make mesothelioma more resistant to cytotoxic agents such as chemotherapy or photodynamic therapy. Preliminary analysis of TMA staining indicates that patients who experience an early disease recurrence in our series exhibit significantly higher STAT3 expression. Figure 1

      Conclusion
      This study is among the largest to describe the survival after initial recurrence for malignant pleural mesothelioma in patients undergoing definitive surgical management. Patients recurring prior to the median of 11.6 months experienced an aggressive tumor recurrence phenotype with a median 10.3 months from recurrence to death. Patients recurring after the median of 11.6 months experienced a relatively indolent disease course with a median survival of 37 months after recurrence. Further evaluation and additional studies are necessary to confirm if elevated STAT3 expression could be a poor prognostic factor for patients undergoing radical pleurectomy, photodynamic therapy and chemotherapy.