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D. Jones
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MA 13 - New Insights of Diagnosis and Update of Treatment (ID 674)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:S. Ishikura, H. Nakayama
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 311 + 312
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MA 13.14 - Surgical Outcomes and Survival Analysis Following Second Pulmonary Resection for Non-Small Cell Lung Cancer (ID 9374)
15:45 - 17:30 | Author(s): D. Jones
- Abstract
- Presentation
Background:
The early detection and improved survival of resected non-small cell lung cancer (NSCLC) may increase the number of patients who eventually undergo subsequent pulmonary resection. We investigated the surgical outcomes and survival of patients following second and third pulmonary resections for NSCLC.
Method:
Patients who underwent second or third pulmonary resections without induction therapy for synchronous or metachronous NSCLC (511 patients, 535 procedures, 2000-2014) were included in the analysis.
Result:
Among 535 operations, 361 (67%) were sublobar resection and 103 (19%) were performed by minimally invasive approach, with the proportion of minimally-invasive procedures increasing in recent years (Fig. 1). The majority of re-resections were performed within 4 years of the previous resection (Fig. 2). Risk regression analysis demonstrated that predicted postoperative (ppo) FEV1 (p<0.001) and same side operation (p=0.002) were independent risk factors for severe complications (CTCAE grade ≧ 3; N=45). Multivariable Cox regression analysis revealed that age at subsequent surgery, male sex, ppoDLCO, interval from prior surgery, and tumor stage were independently associated with overall survival.
Conclusion:
In this large cohort of pulmonary re-resections for NSCLC, predicted postoperative pulmonary function tests were indictive of major complications and overall survival. Figure 1 Figure 2
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MA 15 - Lung Cancer Biology II (ID 670)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Biology/Pathology
- Presentations: 1
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MA 15.09 - Circumferential Distribution and Distance from Main Tumor of Tumor Spread Through Air Spaces (STAS) Are Prognostic (ID 10143)
15:45 - 17:30 | Author(s): D. Jones
- Abstract
- Presentation
Background:
The prognostic impact of the presence of tumor spread through air spaces (STAS) has been reported in lung adenocarcinoma (ADC). The aim of this study is to investigate the prognostic impact of the distribution, distance from the primary tumor, and quantification of STAS.
Method:
A cohort of 394 patients with pathologic stage I lung ADC (2012-2014) were investigated. The distribution of STAS around the tumor was classified into focal or circumferential. The distance of STAS was evaluated by counting the number of air spaces between the farthest STAS and the tumor edge. STAS was quantified by counting the number of STAS areas in the three most STAS- dense 20x high power fields (HPFs). The recurrence free probability (RFP) was analyzed by the Kaplan-Meier method with a log-rank test.
Result:
STAS was present in 211 (54%) cases. The presence of STAS was associated with a higher risk of recurrence (5-y RFP in STAS-positive vs. STAS-negative; 78% vs 90%, p<0.001, Fig 1A). Circumferential STAS was associated with a higher risk of recurrence than focal STAS (5-y RFP in circumferential vs. focal; 67% vs 87%, p=0.027, Fig 1B). A longer distance of STAS was associated with a higher risk of recurrence (5-y RFP >7 alveoli vs.≤7 alveoli, 69% vs. 91%, p=0.003, Fig 1C). Quantification of STAS was not prognostic (5-y RFP in >3/HPFs vs. ≤3/HPFs, 75% vs. 88 %, p=0.15). Figure 1 X
Conclusion:
Beyond just the presence of STAS, the distribution and distance of STAS can further stratify the risk of recurrence in stage I lung ADC.
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OA 03 - Mediastinal and Esophageal Tumor: Insight and New Treatment (ID 654)
- Event: WCLC 2017
- Type: Oral
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:M. Chida, Jhingook Kim
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 311 + 312
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OA 03.03 - Phase II Trial of Cetuximab and Chemotherapy Followed by Surgical Resection for Locally Advanced Thymoma (ID 10288)
11:00 - 12:30 | Author(s): D. Jones
- Abstract
- Presentation
Background:
The mainstay of treatment for thymoma is surgery with neoadjuvant chemotherapy recommended to patients with locally advanced disease. EGFR is overexpressed in thymoma. Clinical responses to single-agent cetuximab have been reported in patients with advanced cetuximab. We conducted this two-site prospective phase II trial of cetuximab combined with a standard induction chemotherapy regimen of cisplatin, doxorubicin and cyclophosphamide (PAC) in patients with locally advanced thymoma prior to surgical resection.
Method:
Patients with clinical Masaoka stage III-IVA thymoma were treated with cetuximab (250mg/m[2] weekly x 4 weeks) followed by cetuximab (250 mg/m[2] weekly) combined with cisplatin (50mg/m[2]), doxorubicin (50 mg/m[2]) and cyclophosphamide (500mg/m[2]) 3 weeks x 4 cycles). Radiographic response was assessed by CT using RECIST 1.1 and FDG-PET using PERCIST. All patients went on to surgery after completion of induction therapy. The primary endpoint was major pathologic response (MPR, >90% treatment effect). Planned enrollment was 18 patients in first stage of a two stage design. If 1 MPR was observed, then enrollment would expand to 28 patients.
Result:
Eighteen patients were enrolled: 8 women, median age 53 (range 32-73). WHO Histologic subtype A: 2, AB: 3, B1: 3, B2: 7, B3: 3. Final Masaoka stage I: 2, II: 2, III: 5, IVA: 9. There were no responses to cetuximab alone by RECIST criteria, although 1 patient had a 25% reduction in indicator lesions. Response rate (CR+PR), in evaluable patients after complete treatment course was 50% (8/16, 95% CI 28-72%). Partial responses by PERCIST criteria were seen on PET in 11/18 (61%) evaluable patients. There were no MPRs. R0 resection was obtained in 7 patients; 5 had R1 and 6 had R2 resections.
Conclusion:
The addition of cetuximab to PAC chemotherapy did not lead to pathologic complete responses in the neoadjuvant setting. Cetuximab alone appears to have little effect during 4 weeks of treatment. There was no apparent increase in radiographic response rate with the addition of cetuximab to PAC chemotherapy compared to historical series.
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OA 10 - Liquid Biopsy for Genomic Alterations (ID 678)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Adrian G. Sacher, Pasi A Jänne
- Coordinates: 10/18/2017, 11:00 - 12:30, F201 + F202 (Annex Hall)
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OA 10.03 - Liquid Biopsy in the Lung Cancer Clinic: A Prospective Study of Plasma DNA next Generation Sequencing to Guide Matched Therapy (ID 8218)
11:00 - 12:30 | Author(s): D. Jones
- Abstract
- Presentation
Background:
Liquid biopsy for plasma circulating tumor DNA (ctDNA) next generation sequencing (NGS) is now commercially available and increasingly adopted in clinical practice with a paucity of evidence based guidance. We set out to prospectively determine the utility of plasma ctDNA NGS in the lung cancer clinic.
Method:
Patients (pts) with advanced NSCLC who were driver unknown or resistance mechanism unknown were eligible. Pts were enrolled prospectively at Memorial Sloan Kettering (NY, USA) and Northern Cancer Institute (Sydney, Australia). Peripheral blood was collected in Streck tubes (10-20mL) and sent to Resolution Bioscience (Bellevue, WA) for targeted NGS of extracted DNA using a bias corrected hybrid capture 21 gene assay in a CLIA laboratory with unique reads at 3000x and sensitive detection at variant allele frequency above 0.1%. Clinical endpoints included detection of oncogenic drivers, turnaround time, comparison to tissue NGS when available, and ability to match pts to targeted therapy along with their treatment outcomes.
Result:
Seventy-six pts were prospectively accrued. Plasma NGS detected an oncogenic driver in 36% (27/76) of pts, of whom 14% (11/76) were matched to targeted therapy; including pts matched to clinical trials for HER2 exon 20 insYVMA, BRAF L597Q and MET exon14. Of the 10 evaluable pts, 10 partial responses were observed. Mean turnaround time for plasma was 6 days (3-12) vs 21 days (16-30) for tissue (P <0.0001). Plasma ctDNA was detected in 60% (46/76) of pts; detection rate was 46% (16/35) if blood was drawn on active therapy and 73% (30/41) if drawn off therapy, either at diagnosis or progression (Odds ratio 0.31, 95% CI 0.12 – 0.81; P=0.02). Of the 25 concurrent tissue NGS performed to date, there was a 96% plasma concordance with tissue and a 60% tissue concordance with plasma for driver mutations.
Conclusion:
In pts who were driver or resistance mechanism unknown, plasma NGS identified a variety of oncogenic drivers with significantly shorter turnaround time compared to tissue NGS, and matched patients onto targeted therapy with clinical benefit. Plasma ctDNA is best detected at diagnosis of metastatic disease or at progression. A positive finding of an oncogenic driver in plasma is highly specific and can immediately guide treatment, but a negative finding may still require tissue biopsy. Our findings provide evidence to support the incorporation of plasma NGS into practice guidelines.
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P1.13 - Radiology/Staging/Screening (ID 699)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.13-003 - Recurrence Dynamics in Resected Pathological Stage I Lung Adenocarcinoma Depend on the IASLC/ATS/ERS Histological Subtype (ID 9423)
09:30 - 16:00 | Author(s): D. Jones
- Abstract
Background:
Current practice guidelines recommend uniform follow-up protocol for all stage I lung adenocarcinoma (ADC) patients who underwent surgical resection. We hypothesized that the annual recurrence hazard of resected pathological stage I lung ADC patients vary according to the IASLC/ATS/ERS histological subtype.
Method:
Pathological stage I lung ADC patients who had undergone complete resection (R0) without induction therapy (N=1572, 1995-2012) were analyzed.
Result:
Among 1572 patients, 271 (18.5%) recurrences were identified (median follow-up 64.0 months) with highest peak of recurrence within first two years following resection. Patients who had undergone sublobar resection showed higher recurrence rate than those who had undergone lobectomy (Fig. 1A). The recurrence hazard increased as a function of the percentage of micropapillary (MIP) pattern (Fig. 1B), while the solid pattern contributed to the early recurrence (Fig. 1C). According to the presence of MIP and/or solid (SOL) pattern, the recurrence hazard is well stratified. Tumors without micropapillary and solid subtype show no peak with 2% of annual recurrence hazard within 10 years following resection, while tumors with both MIP and SOL patterns have the highest peak within 2 years compared to other MIP and SOL combinations.
Conclusion:
Patients with resected pathological stage I lung ADC show structured recurrence dynamics well stratified with the high risk histological subtypes, providing clinically useful prognostic information for patients and physicians. Figure 1
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P2.05 - Early Stage NSCLC (ID 706)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.05-021 - Occult Nodal Metastasis Following Lobectomy for Clinical Stage I Lung Adenocarcinoma: Implications for Sublobar Resection (ID 9436)
09:30 - 16:00 | Author(s): D. Jones
- Abstract
Background:
We investigated the incidence and location of occult nodal metastasis (ONM) in patients who had undergone lobectomy and lymph node dissection for clinical stage I lung adenocarcinoma (ADC). We performed a risk regression analysis to identify any associated radiologic and pathologic factors.
Method:
Clinical stage I lung ADC patients (stage II and III were excluded by CT and FDG-PET/CT scans) who underwent lobectomy and systematic lymph node dissection (N=715, 2005-2011) were included in the analysis. ONM were defined as pathologically diagnosed metastatic lymph nodes that are not suspected to be involved by cancer on both CT and PET scans.
Result:
Among 715 patients, 75 (10.5%) ONM were identified: 64 (85%) hilar or peribronchial and 32 (43%) mediastinal. Multivariable risk regression analysis identified tumor diameter, SUVmax, and lymphovascular invasion as risk factors (P<0.01). The incidence of subcarinal lymph node (LN) metastasis was very low among patients whose primary tumors were in the right upper lobe or left upper division (N=1/439, 0.2%). Lower mediastinal LN metastasis was rarely identified only when the primary tumor was located in the right lower or left lower lobe (N=2/210, 1.0%).
Conclusion:
One in ten patients with clinical stage I lung adenocarcinoma showed occult nodal metastases, with the highest incidence in hilar lymph nodes; this observation may be relevant for clinicians when considering sublobar resection for these patients. Figure 1
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P3.13 - Radiology/Staging/Screening (ID 729)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.13-019 - Preoperative Needle Biopsy Does Not Increase the Risk of Pleural Recurrence in ≤3cm Lung Adenocarcinoma (ID 9526)
09:30 - 16:00 | Author(s): D. Jones
- Abstract
Background:
Percutaneous transthoracic needle biopsy (NB) has been widely used for the preoperative diagnosis of lung nodules. It has been proposed that the risk of pleural recurrence is high following lung resection in patients who underwent preoperative NB for sub-pleural nodules (Kashiwabara, et al. Cancer Invest 2016; Wang, et al. Sci Rep 2017). The aim of this study is to investigate the prognostic impact of preoperative NB for pleural recurrence in patients with early-stage lung adenocarcinoma (ADC).
Method:
Patients who underwent lung resection for pathologic stage I (≤3cm) lung ADC were included in the analysis (1995-2014, n=992; NB group 626 patients and no-NB group 366 patients). We compared the clinicopathologic characteristics and recurrence free probability (RFP, separately analyzed for any, locoregional, pleural, and distant recurrence) between NB and no-NB groups. The risk of pleural recurrence was evaluated in tumors both with and without visceral pleural invasion (VPI).
Result:
The NB cohort was associated with older age and larger tumor size compared to the no-NB cohort (p<0.05). There was no statistical difference in the incidence of VPI (VPI in NB, 12% vs. VPI in non-NB, 15%, p=0.2). In RFP analysis by Kaplan-Meier method with log-rank test, there was no statistical difference between NB and no-NB groups (NB vs. non-NB: 5-year RFP for any recurrence, 86% vs. 86%, p=0.8; locoregional recurrence, 93% vs. 94%, p=0.7; pleural recurrence, 98% vs. 96%, p=0.14; and distant recurrence 94% vs. 93%, p=1). In tumors both with and without VPI (n=128 and n=864, respectively), the risk of pleural recurrence was not higher after NB (Figure; 5-year RFP for pleural recurrence [NB vs. no-NB]: VPI positive, 93% vs. 83%, p=0.3; VPI negative, 98% vs. 97%, p=0.4). Figure 1
Conclusion:
Preoperative needle biopsy was not associated with an increased risk of pleural recurrence following lung resection.
