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E. Glatstein



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    MO09 - Mesothelioma I (ID 120)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track:
    • Presentations: 1
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      MO09.13 - 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): E. Glatstein

      • 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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    MO22 - Advanced Disease and Outcomes (ID 103)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Surgery
    • Presentations: 1
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      MO22.11 - Prospective Study of Surgery with Curative Intent and Intraoperative Photodynamic Therapy to Achieve Long-term Pleural Control and Improve Overall Survival for Patients with Non-small Cell Lung Cancer with Pleural Dissemination (ID 3141)

      10:30 - 12:00  |  Author(s): E. Glatstein

      • Abstract
      • Presentation
      • Slides

      Background
      Non-small cell lung cancer (NSCLC) with pleural spread carries a dismal prognosis of 6-9 months median survival. Standard treatment is palliative chemotherapy. Surgery typically has no role, with studies showing no overall survival (OS) benefit and high rates of local recurrence of up to 90% due to microscopic residual disease following resection. This study investigated the use of surgery with the intent of achieving a gross total resection and intraoperative photodynamic therapy (PDT) to target microscopic residual disease for patients with NSCLC with pleural metastasis to improve local control and OS.

      Methods
      All patients with NSCLC with pleural metastasis treated with definitive surgery and PDT (porfimer sodium, 24hr drug-light interval, 630nm, 30-60J/cm[2]) from 1997-2012 on either of two IRB-approved prospective clinical trials were assessed. Progression-free survival (PFS) and OS were defined as the time from surgery to recurrence and death, respectively, or to last contact. Pleural control was defined as absence of ipsilateral pleural disease after surgery, whereas locoregional control was defined as absence of lung parenchymal or intrathoracic nodal disease.

      Results
      34 consecutive patients were assessed, all with ECOG performance status 0-1. The cohort was 50% male, predominantly Caucasian (85%), and a median of 55yrs at the time of surgery (range, 35-73yrs). Most had adenocarcinoma (79%), clinical N2 nodal metastasis (64%), and received neoadjuvant chemotherapy (94%) and/or radiotherapy (12%). Over half (56%) underwent pneumonectomy, whereas 38% received a lesser anatomic resection. Two patients were found intraoperatively to have unresectable disease due to pericardial effusion (n=1) or trans-diaphragmatic extension (n=1). Pathologic staging was pT4N0 (24%) or pT4N2 (76%). Four patients (3/19 pneumonectomy, 1/13 lung-sparing) suffered peri-operative mortality (day 11-98), with one death attributable to PDT (ARDS, day 11). Following surgery/PDT, 59% of patients received mediastinal radiotherapy (median 50.4Gy/1.8Gy) and 50% received chemotherapy. Pleural recurrence rates and OS were similar for patients undergoing pneumonectomy or other procedures (p>0.05 for both). Cohort median OS was 21.4 months (0.4-161.1 months), and survival rates were 59% at 1yr and 41% at 2yrs. Median overall PFS was 7.5 months, with numerous patients achieving durable disease-free intervals (mean PFS 18.4 months). Median pleural PFS was 13.6 months, with pleural recurrences occurring in only 32%. Overall, 79% experienced recurrence or unresectable disease progression, and distant failure was most commonly observed (53%).

      Conclusion
      This study demonstrates that surgery and intraoperative PDT can achieve durable local control and prolonged survival for NSCLC patients with pleural dissemination. Compared with current standard treatment, which offers a median survival of 6-9 months from pleural metastasis diagnosis, our cohort lived a median of 24.7 months from pleural diagnosis and 21.4 months from surgery/PDT. This study also demonstrates that surgery/PDT can be performed with acceptable morbidity. Distant recurrence was the most common failure, indicating need for improved adjuvant systemic therapy. These results are sufficiently encouraging to warrant further study and suggest that stage IVA NSCLC patients with pleural dissemination, good performance statuses, disease limited to one hemithorax, and of the mind to be aggressive about their disease could be considered for this investigational treatment approach.

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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 - 16:30  |  Author(s): E. Glatstein

      • 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.