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S. Armato
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MINI 38 - Biology and Prognosis (ID 167)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:R. Tsuchiya, M. Wynes
- Coordinates: 9/09/2015, 18:30 - 20:00, 702+704+706
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MINI38.11 - Tumor Volume and Epithelioid Differentiation Are Independent Predictors of Survival in Malignant Pleural Mesothelioma (ID 2428)
18:30 - 20:00 | Author(s): S. Armato
- Abstract
- Presentation
Background:
Maximal cyto-reductive surgery with adjuvant therapy provides survival advantage in selected patients with malignant pleural mesothelioma (MPM). Extended pleurectomy and decortication (EPD), a lung sparing procedure, provides an opportunity to measure the tumor volume. We hypothesized that tumor volume is a better predictor of survival than the T and N, because it represents tumor burden more accurately. Currently the significance of epithelioid differentiation in the biphasic histology also remains poorly understood. We report our experience with patients undergoing EPD and the implication of tumor volume and epithelioid differentiation in overall survival.
Methods:
We evaluated 116 patients who underwent EPD for MPM. The following variables were assessed: age, gender, histology, tumor volume and pathological T and N stage. The tumor volume of resected specimens was measured using a water displacement method. All histological examinations were performed by a single pathologist, and the percent epithelioid histology was estimated in all patients. A Cox regression model was used to identify significant predictors of survival. Kaplan-Meier was used to summarize overall and subgroup survival.
Results:
There were 95 males and 21 females with a median age of 68 years (range 43-88 years). Epithelioid differentiation was 100% in 60 patients, 50-95% in 35 patients, and less than 50% in 21 patients (no patient with pure sarcomatoid histology was included in this report). Mean tumor volume was 642+/- 400ml. Tumor volume was between 100-299cc in 20 patients, between 300-599cc in 37 patients, and >600cc in 54 patients. In 5 patients the volume was not estimated. Six patients (5%) died within 30 days. Two-year survival from EPD was 28%. Median survival was 15.7 months. Percent epithelioid differentiation (p=0.0004) and tumor volume (p=0.001) were significant predictors of survival. T (p=0.05) stage, but not N stage, was a significant predictor of survival. Tumor volume was a predictor of T stage (p=0.05). No relationship between N stage and either tumor volume or histology was observed.
Conclusion:
Percent epithelioid differentiation and tumor volume are independent predictors of survival in MPM patients undergoing EPD.
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-012 - Using Computed Tomography Scans to Assess the Histology of Malignant Pleural Mesothelioma (ID 3003)
09:30 - 17:00 | Author(s): S. Armato
- Abstract
Background:
The purpose of this study is to assess the histology of malignant pleural mesothelioma using computed tomography (CT) based imaging.
Methods:
28 patients with malignant pleural mesothelioma were used (histologies: 17 epithelioid, 11 biphasic). A CT scan was acquired for each patient prior to surgical resection of the tumor. A radiologist identified and outlined the tumor boundary on each CT section that demonstrated tumor. These outlines were analyzed to determine the total volume of disease present, the mean volume of disease per outlined section, and the distribution of Hounsfield Unit (HU) values throughout the outlined tumor. These parameters were used to differentiate tumors of epithelioid and biphasic histologies. For each parameter, cutoffs were determined to maximize the extraction of biphasic cases from the entire cohort, while minimizing the extraction of epithelioid cases.
Results:
Discernable differences were extracted from the images of the two different histologies of the disease. Figure 1 shows the mean HU value, the standard deviation and skew in the distribution in the HU values, and the volume of tumor represented on each CT section demonstrating disease. With regard to HU distribution, the biphasic cases generally had a higher mean HU value. For example, 73% of the biphasic cases had a mean value greater than 30, compared to only 29% of the epithelioid cases. Biphasic cases also tend to have a more negative skew in their HU distribution; 73% of biphasic cases had a skew value less than -1, compared to 35% of epithelioid cases. It was also seen that biphasic cases also tended to have a higher volume of tumor present throughout their disease presenting CT sections. There were promising results from extracting the biphasic cases by using optimized cutoffs from gathered data. The criteria used were as follows: Cases that exhibited more than 9 mL of tumor per outlined CT section, or exhibited a mean HU value greater than 10 as well as a skew in HU values less than -1 were extracted from the cohort and identified as biphasic. Of the cases that match these criteria, 10 were actually biphasic while 6 were actually epithelioid. These results are 91% specific, missing only one biphasic case, and 65% specific, correctly excluding 11 of the 17 epithelioid cases. Figure 1 Figure 1 – Comparison of Epithlioid and Biphasic cell types.
Conclusion:
This study demonstrates that CT-based imaging may be a useful tool for the assessment of tumor histology through image analysis.
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P2.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 225)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.08-010 - Phase II Study of the Anti-PD-1 Antibody Pembrolizumab in Patients with Malignant Mesothelioma (ID 3020)
09:30 - 17:00 | Author(s): S. Armato
- Abstract
Background:
Mesothelioma is a frequently "inflamed" tumor. We previously identified PD-L1 expression, a CD8 infiltrative pattern, and the presence of PD-1/PD-L1 immune checkpoints in about 1/3 of mesothelioma tumors, similar to the phenotype found in malignancies such as melanoma that benefit from immune checkpoint blockade (Kindler and Seiwert, ASCO 2014). Based on these data, we have initiated a single-center phase II trial (NCT02399371) of the anti-PD-1 antibody pembrolizumab in previously-treated mesothelioma patients. The rationale for this study is further supported by recent data from a phase IB multi-cohort study of pembrolizumab in PD-L1 positive solid tumors, in which an objective response rate of 28% and a disease control rate of 76% was observed in 25 pleural mesothelioma patients, who received 10 mg/kg pembrolizumab every 2 weeks (Alley, AACR 2015).
Methods:
Eligible patients have histologically-confirmed pleural or peritoneal mesothelioma, measurable disease, PS 0-1, disease progression on or after treatment with pemetrexed plus cis- or carboplatin, no more than 2 prior lines of cytotoxic therapy, normal organ function, and tissue available for correlative studies. Patients receive a flat dose of 200 mg pembrolizumab intravenously every 3 weeks. CT scans are obtained every 9 weeks. The primary objectives are: 1) to determine the objective response rate in A] an unselected population and in B] a PD-L1 positive population, and 2) to determine the optimal threshold for PD-L1 expression using the 22C3 antibody-based IHC assay. Secondary objectives include progression-free and overall survival, disease control rate, and toxicity. Correlative studies are intended to characterize the T-cell inflamed phenotype in mesothelioma via CD8, CD4, and PD-L1 staining, immune related gene expression signatures (Nanostring), and determination of other immune escape mechanisms including T-regulatory cells (FOXP3 expression), IDO expression, MDSCs, and other checkpoints/co-stimulatory signals by immunohistochemistry and/or flow cytometry. A single-stage binomial design will be used. Part A requires ≥ 3 responses in 35 patients. Part B, which uses PD-L1 pre-selection (optimal expression pattern and threshold determined in cohort A), requires ≥ 6 responses in 30 patients. Funded in part by a grant from the Mesothelioma Applied Research Foundation.
Results:
Not applicable.
Conclusion:
Not applicable.
