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Akifumi Nakamura
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P1.06 - Mesothelioma (ID 169)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.06-05 - Clinical Features and Outcomes of Recurrence After Pleurectomy/Decortication for Malignant Pleural Mesothelioma (ID 1182)
09:45 - 18:00 | Presenting Author(s): Akifumi Nakamura
- Abstract
Background
Malignant pleural mesothelioma (MPM) is an aggressive tumor while most patients experience recurrence after multimodality treatment. However, few clinical studies have been conducted to evaluate the recurrence pattern and survival after Pleurectomy/decortication (P/D) for MPM.
Method
We reviewed the patients who registered in the prospective MPM database of our hospital surgery program between September 2012 and December 2017. Eligibility criteria were age ≤80 years, histological subtype on pleural biopsy was epithelioid, clinical stage T1-3N0-1M0 (8th edition), an Eastern Cooperative Oncology Group performance status of 0-1, no major comorbidity. Neoadjuvant chemotherapy (NAC) consisted of pemetrexed followed by cisplatin was performed in all patients who met previously mentioned inclusion criteria. After NAC for three cycles, curative-intent surgery was planned in patients who showed no apparent tumor progression. In our hospital, P/D was introduced in September 2012, and since then P/D was main operative method for MPM. After P/D, If the patients keep good general condition, the patients underwent adjuvant chemotherapy consisted of pemetreced follow by cisplatin. The subjects were 90 patients who underwent NAC followed by P/D from September 2012 to December 2017. Survival and recurrence were calculated by the Kaplan-Meier method using the log rank test. Clinical factors related to survival after recurrence was assed by a multivariable analysis using Cox proportional hazards model.
Result
Between September 2012 and December 2017, 140 consecutive patients were eligible for multimodality treatment. All patients completed neoadjuvant chemotherapy. Of these, 112 patients proceeded to surgery, and the remaining 28 patients didn’t because of progressive disease (N= 20) or because they refused to provide consent (N= 8). Of 112 patients who proceeded to surgery, 12 patients underwent Extrapleural pneumonectomy, 10 patients underwent exploratory thoracotomy. Finally, 90 patients underwent P/D.
Of 90 patients, 65 patients (72.2%) completed multimodality treatment. The 1-year and 3-year overall survival rates after diagnosis were 93.3% and 65.3%, respectively. A recurrence developed in 57 (63.3%). The median time to recurrence was 19.0 months. 1-year and 3-year recurrence free survival were 69.7% and 34.0%, respectively.
In the initial recurrence, local recurrence only was developed in 39 patients (68.4%), distant recurrence only in 6 patients (10.5%), and both local and distant recurrence in 12 patients (21.1%). 1-year survival rates after recurrence was 59.5%. 43 patients (75.4%) received a treatment for recurrence. On multivariable analysis, treatment for recurrence (hazard ratio, 0.16; 95% confidence interval, 0.06–0.41: P < 0.0001) and disease-free interval greater than 12 months (hazard ratio, 0.34; 95% confidence interval, 0.14 –0.79; P = 0.01) were identified as independently significant prognostic factors of survival after recurrence.
Conclusion
The local recurrence remain the most frequent pattern of recurrence after P/D. Most of patients who had recurrence after P/D enabled treatment for recurrence. Treatment for recurrence and disease-free interval greater than 12 months are important prognostic factors of survival after recurrence.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-62 - TCR Repertoire Analysis of Peripheral CD8+PD-1+ T Cells Is Effective as a Predictive Biomarker for Response to the Immune Checkpoint Inhibitor (ID 1668)
10:15 - 18:15 | Author(s): Akifumi Nakamura
- Abstract
Background
Immune checkpoint inhibitors are effective in NSCLC patients. As patient selection is important, many biomarkers have been studied. We developed a method to predict the effect of immune checkpoint inhibitors using peripheral blood. Tumor infiltrating lymphocyte (TIL) sensitizes to neoantigens, some of them migrate to peripheral blood. We measured tumor mutation burden (TMB) of resected specimen and T-cell receptors (TCRs) diversity of peripheral CD8+PD-1+ T cells, examined response rate and prognosis.
Method
The study included NSCLC patients who relapsed after surgery and chemotherapy failed. Peripheral blood mononuclear cells (PBMC) was collected from patients before 1st administration of nivolumab. CD8+PD-1+ T cells were subjected to FACS sorting, NGS-based TCR repertoire analysis was performed by Repertoire Genesis Inc., and TCR diversity was evaluated statistically.
Result
There were no differences in the proportion of PD-1+ in CD8+ T cells between responders and non-responders. TCR α diversity based on DE50 was significantly higher among responders than non-responders (P < 0.01). TCR β diversity was also significantly higher among responders than non-responders (P < 0.01). Progression-free survival (PFS) and Overall survival (OS) were better in TCR diversity high group than that TCR diversity low group (P=0.01). TMB was not significantly different between responder and non-responder. PFS and OS were not significantly different between TMB high (≧10) group and TMB low (<10) group.
Conclusion
Significant therapeutic effect of nivolumab was observed in NSCLC patients whose peripheral CD8+ PD-1+ T cells had highly diverse TCR. This study suggests the TCR diversity of peripheral CD8+PD-1+ T cells is effective as a predictive biomarker for response to the immune checkpoint inhibitor.
