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J. Nitadori
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MA15 - Immunotherapy Prediction (ID 400)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:O. Arrieta
- Coordinates: 12/07/2016, 14:20 - 15:50, Schubert 1
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MA15.01 - Immunogram for Cancer-Immunity Cycle towards Personalized Immunotherapy of Lung Cancer (ID 4519)
14:20 - 14:26 | Author(s): J. Nitadori
- Abstract
Background:
The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of anti-tumor immunity as a dynamic spacio-temporal process is required for each individual patient. To this end, we developed an "immunogram for the cancer-immunity cycle" using next-generation sequencing.
Methods:
Whole-exome sequencing and RNA-Seq were performed in 20 non-small cell lung cancer patients (12 adenocarcinoma, 7 squamous cell carcinoma, and 1 large cell neuroendocrine carcinoma). Mutated neoantigens and cancer-germline antigens expressed in the tumor were assessed for predicted binding to patients’ HLA molecules. The expression of genes related to cancer-immunity was assessed and normalized; immunogram was drawn in a radar chart composed of 8 axes reflecting 7 steps of cancer-immunity cycle.
Results:
Distinctive patterns of immunogram were observed in lung cancer patients: T-cell-rich and T-cell-poor. Patients with T-cell-rich pattern had gene signatures of abundant T cells, Tregs and MDSCs, checkpoint molecules and immune-inhibitory molecules in the tumor, suggesting the presence of counter regulatory immunosuppressive microenvironment. Unleashing of counter regulations, i.e. checkpoint inhibitors, may be indicated for these patients (Figure A). Immunogram of T-cell-poor phenotype reflected lack of anti-tumor immunity, inadequate DC activation, and insufficient antigen presentation in the tumor (Figure B). When the immunograms were overlaid within each tumor histology, no typical pattern was elucidated. Both T-cell-rich and T-cell-poor phenotypes were present in each histology, suggesting that histology cannot necessarily reflect the cancer-immunity status of the tumor (Figure C,D). These results were consistent with previous studies showing that clinical responses of checkpoint blockade were not easily predicted by the histology. Figure 1
Conclusion:
Utilizing the immunogram, the landscape of the tumor microenvironment in each patient can be appreciated. Immunogram for the cancer-immunity cycle can be used as an integrated biomarker and thus may become a helpful resource toward optimal personalized immunotherapy.
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OA12 - SBRT and Other Issues in Early Stage NSCLC (ID 383)
- Event: WCLC 2016
- Type: Oral Session
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:D. De Ruysscher, M.R. Mueller
- Coordinates: 12/06/2016, 11:00 - 12:30, Strauss 2
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OA12.06 - A Retrospective Analysis of Patients with Small Lung Adenocarcinoma (≤2cm) by New World Health Organization Classification (ID 5844)
11:55 - 12:05 | Author(s): J. Nitadori
- Abstract
- Presentation
Background:
We have recently demonstrated that the presence of the Spread Through Air Spaces (STAS) and the variety of histologic subtypes increase the risk of recurrence after resection for small lung adenocarcinoma (ADC). Currently, the new World Health Organization classification of lung cancers was revised and newly prescribed to describe the presence of each histologic subtypes and STAS. The purpose of this study is to examine the risk factor for recurrence other than TNM staging analyzing clinical information retrospectively.
Methods:
All available tumor slides from patients with clinical stage I, therapy-naive, surgically resected solitary lung ADC ≤2 cm in size (1998-2015) were reviewed. Each tumor was evaluated by comprehensive histologic subtyping, and the percentage of each histologic component was recorded in 5% increments. STAS was defined as the spread of tumor cells into air spaces in the lung parenchyma adjacent to the main tumor according to the WHO classification. Recurrence-free probability (RFP) was estimated using the Kaplan-Meier method.
Results:
354 patients met inclusion criteria (52.3% men; median age: 67yrs; median tumor size: 1.3cm; 325 stage IA/ 29 stage IB; 91 partial resection/ 22 segmentectomy / 241 lobectomy or pneumonectomy). The prognosis didn’t differ significantly between sublobar resection group and lobectomy or pneumonectomy group (5-year RFP: 88.4% (N=113) vs. 91.9% (N=241), P=.162). Presence of STAS was identified in 74 cases (20.9%) (36 Micropapillary pattern / 55 Solid pattern / 15 Single cells). STAS was significantly associated with recurrence (5-year RFP: 94.3% vs. 76.2%, P < .0001). Histologic subtypes were 62 adenocarcinoma in situ (18%), 110 minimally invasive adenocarcinoma (31%) and 182 invasive adenocarcinoma (51%). The recurrence after sublobar resection was seen in 13 cases (1 partial resection (4.5%) / 12 segmentectomy (13%), 5 STAS (+)/ 8 STAS (-), 6 solid predominant / 5 acinar predominant / 2 lepedic predominant, 5 pulmonary recurrence / 4 lymph node recurrence / 2 local recurrence / 2 others). Patients with solid component had significantly worse prognosis (5-year RFP: 71.7% (N=83) vs. 96.3% (N=271), P<.0001). Among them, patients with sublobar resection had significantly more recurrence than with lobectomy or pneumonectomy (5-year RFP: 51.4% (N=19) vs. 77.7% (N=64), P=.0021).
Conclusion:
The patients of small ADC with STAS or solid component had worse prognosis. The patients after sublobar resection with solid component should be made follow-up closely. We propose that the presence of those features should be considered a factor to upgrade the pathologically defined T stage.
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-035 - Concomitant Driver Mutation Determines Tumor Growth in EGFR Mutation-Positive Lung Adenocarcinoma (ID 5397)
14:30 - 14:30 | Author(s): J. Nitadori
- Abstract
Background:
In the practice of precision medicine, understanding tumor characteristics in the individual patient is crucial. The aim of this study was to analyze tumor aggressiveness from two perspectives: actual growth rate calculated from the tumor; and molecular profiles obtained by next-generation sequencing.
Methods:
Participants comprised patients who underwent preoperative CT two or more times. DNA and RNA of 10 lung adenocarcinoma tumor samples were extracted. Whole-exome and -transcriptome data were obtained, and somatic mutations were detected. Preoperative CT scans were retrospectively reviewed and volume doubling time (VDT) of each tumor was calculated using a modified Schwarz equation.
Results:
Median VDT was 104 days (range, 42-653 days). Median number of somatic missense mutations was 20 (range, 7-306). EGFR mutations were present in 6 patients. Patients were divided into two groups by VDT for further analyses: Slow group with VDT ≥104 days (n=5); and Rapid Group with VDT <104 days (n=5). All patients with EGFR mutation without concomitant KRAS mutation were in the Slow Group. In contrast, a patient with concomitant mutations of EGFR and KRAS showed a considerably rapid growing tumor with a VDT of 45 days. A patient with concomitant mutations in EGFR and PIK3CA had a relatively slow-growing tumor, although VDT was the shortest in the Slow Group (120 days). Figure 1
Conclusion:
EGFR mutation was associated with slow growth of the tumor, although the growth rate may be influenced by concomitant mutation of other driver genes. This may be one of the reasons that the clinical response of tyrosine kinase inhibitors are poor in some patients with EGFR mutation. Assessment of tumor aggressiveness by molecular profiling and by sequential CT are both important for the practice of precision medicine.
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P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.01-022 - Impact of Histologic Subtype and Spread through Air Spaces (STAS) in Stage III (N2) Lung Adenocarcinoma (ID 5446)
14:30 - 14:30 | Author(s): J. Nitadori
- Abstract
Background:
Approximately 15% of patient with non-small cell lung cancer (NSCLC) is present with stage III (N2) disease. The patient prognosis after complete resection for pathological N2 NSCLC remains a significant concern. Currently, the new World Health Organization classification of lung cancers was revised and newly prescribed to describe the presence of each histologic subtype in adenocarcinoma (ADC) and the Spread Through Air Spaces (STAS). The purpose of this study is to examine the relationship between histologic subtype and patient outcome, especially for metastatic lymph node, and clinicopathologic features of STAS in stage III (N2) lung ADC according to new WHO classification retrospectively.
Methods:
All available tumor slides from patients with pathological N2, surgically resected lung ADC (1998-2013) were reviewed. Each tumor was evaluated by comprehensive histologic subtyping according to new WHO classification, and the percentage of each histologic component was recorded in 5% increments. We reviewed the histologic subtype in the N2 lymph nodes and relationship between main tumor and N2 lymph nodes. Recurrence-free probability (RFP) and overall survival (OS) were estimated using the Kaplan-Meier method.
Results:
78 patients met inclusion criteria (55% men; median age: 68yrs; 76 stageIIIA/ 2 stageIIIB, 77 lobectomy). The 5-year RFP and OS in N2 lung ADC were 27.8%, 66.8%, respectively. The histologic subtypes such as acinar, micropapillary and solid components in the main tumor were significantly seen in the N2 lymph nodes (P < 0.001, P < 0.05, P < 0.05, respectively). STAS was identified in 48 patients (61.5%) and significantly associated with recurrence (5-year RFP: 18.4% vs. 43.8%, P < 0.05). STAS was significantly associated with presence of micropapillary component (≥ 5%) and lymphatic invasion in the main tumor (P < 0.001).
Conclusion:
Presence of acinar, micropapillary and solid component in the main tumor are associated with metastasizing to lymph nodes. Presence of STAS was significantly associated with increased risk of recurrence in stage III (N2) lung adenocarcinoma.
