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EP1.18 - Treatment of Locoregional Disease - NSCLC (ID 208)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.18-02 - Pattern of Postoperative Recurrence and Clinical Value of Adjuvant Radiotherapy in Completely Resected Stage III/N2 EGFR-Mutant NSCLC (Now Available) (ID 1006)
08:00 - 18:00 | Author(s): Yuan Li
- Abstract
Background
The pattern of postoperative recurrence among patients with stage III/N2 EGFR-mutant non-small cell lung cancer (NSCLC) is seldom reported. Moreover, the clinical value and optimal candidate of postoperative radiotherapy (PORT) for stage III/N2 NSCLC is still controversial.
Method
Consecutive patients who underwent curative resection and were pathologically confirmed EGFR-positive stage III/N2 NSCLC at Fudan University Shanghai Cancer Center from January 2007 to December 2017, were retrospectively enrolled. Serial imaging scans of each patient were intensively examined and the initial recurrence sites were categorized into five groups: thoracic recurrence, brain recurrence, neck recurrence, abdominal recurrence, and bone recurrence. Recurrence-free survival (RFS) were estimated by Kaplan-Meier curves. The Cox proportional hazards model was applied to estimate the association between RFS and clinic-pathological parameters (including age, sex, tumor size, TNM stage, tumor differentiation, tumor histology, lymphovascular invasion, visceral pleural invasion, and EGFR mutation subtypes), as well as a panel of routinely used immunohistochemical markers (including Her2, Ki67, TTF-1, CK20, CK7, CK5/6, p53, RRM1, NapsinA, p40, syn, Bcl-2, CDX2, ERCC1 and p63).
Result
Ninety-one patients were identified, all of whom received adjuvant chemotherapy and 28 of whom received PORT. After a median follow up of 28 (range, 6-103) months, disease recurrence occurred in 62 patients. Thirty-six (58.1%) patients had thoracic recurrence, 15 (24.2%) had bone recurrence, 14 (22.6%) had brain recurrence, 9 (14.5%) had neck recurrence, and 8 (12.9%) had abdominal recurrence. Nineteen patients had multiple sites of initial recurrence. In terms of thoracic recurrence, initial relapse at the resection margin occurred in 1 patients and relapse in the mediastinal or ipsilateral hilar lymph nodes was observed in 11 patients. Ki67≥45% and positive expression of ERCC1 were identified as independent predictors of postoperative recurrence in multivariate analysis. Of note, PORT was not significantly associated with RFS in the whole population (p=0.877). However, among the 62 patients who had at least one of the independent predictors of postoperative recurrence (ie: Ki67≥45%, expression of ERCC1), PORT (n=22) significantly prolonged RFS (p=0.043).
Conclusion
The majority of patients with stage III/N2 EGFR-mutant NSCLC developed their initial recurrence in the thorax. Patients with Ki67≥45% and/or positive expression of ERCC1 have a significant higher risk of postoperative recurrence, who may be the potential candidate for PORT.
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JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)
- Event: WCLC 2019
- Type: Joint IASLC-CSCO-CAALC Session
- Track:
- Presentations: 1
- Moderators:Chunxue Bai, Tony Mok, Yi-Long Wu, Qing Zhou, Nan Wu
- Coordinates: 9/07/2019, 07:00 - 11:15, Toronto (1985)
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JCSE01.19 - Tumor Mutation Score Is More Powerful Than Tumor Mutation Burden in Predicting Response to Immunotherapy in Non-Small Cell Lung Cancer (ID 3433)
07:00 - 11:15 | Presenting Author(s): Yuan Li
- Abstract
Abstract
Background
Tumor mutation burden (TMB) and PD-L1 expression are the two important biomarkers for immune checkpoint inhibitors (ICIs) in lung cancer. However, growing evidences are showing that not all mutations, such as EGFR mutation, are favorable factors in predicting clinical outcome of ICIs and the power of TMB, which is unselective, might be attenuated. Therefore, we developed tumor mutation score (TMS) as better biomarker for response of ICIs in non-small cell lung cancer (NSCLC).
Methods
TMS was defined as the number of genes with nonsynonymous somatic mutations. Mutations were detected by targeted next-generation sequencing (NGS) in 240 NSCLC patients treated with anti-PD-(L)1 monotherapy or in combination with anti-CTLA4. Durable clinical benefit (DCB) was defined as complete response (CR)/partial response (PR)/stable disease (SD) that lasted 6 months. TMS, TMB and PD-L1 expression were compared among DCB and no durable benefit (NDB) NSCLC patients.
Results
The total TMS was significantly correlated with TMB (R=0.98, P<0.001) and performed almost equally to TMB in the analysis. 12 genes and 11 genes (5 sharing genes) were significantly associated with longer progression-free survival (PFS) and response (DCB vs NDB), respectively. The number of mutated genes within these 18 genes were defined as TMS18. In the survival analysis of PFS, the HRs of the high group were TMS19 (HR=0.307, P<0.001), TMB (HR=0.455, P<0.001), and PD-L1 expression (HR= 0.403, P=0.02), separately. Moreover, patients with DCB had significantly higher TMS18 (P<0.001), TMB (P=0.006), and PD-L1 expression (P=0.032). High TMS18 group had highest proportion of CR/PR/SD patients, which was 74.1% (CR/PR/SD: 3/17/20), especially in distinguishing CR patients. Taken together, TMS18 was more powerful than TMB and PD-L1 in predicting response of ICIs in NSCLC.
Conclusion
Simple transformation from unselective TMB to selective TMS greatly enhanced the power of mutations-based biomarkers. TMS in combination with PD-L1 expression might yield better efficiency in predicting response of ICIs in NSCLC with future validation in larger cohorts.
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OA13 - Ideal Approach to Lung Resection and Novel Perioperative Therapy (ID 146)
- Event: WCLC 2019
- Type: Oral Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:Tomasz Grodzki, Kenji Suzuki
- Coordinates: 9/10/2019, 11:30 - 13:00, Toronto (1985)
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OA13.03 - Predicting Postoperative Recurrence in Completely Resected EGFR-Mutant Non-Small Cell Lung Cancer: Value of IHC Markers (Now Available) (ID 998)
11:30 - 13:00 | Author(s): Yuan Li
- Abstract
- Presentation
Background
EGFR mutations are detected in up to 50% of non-small cell lung cancer (NSCLC) and recent studies indicate that EGFR-mutant NSCLC is a heterogeneous disease with varying co-mutations, diverse histologic subtypes and distinct expression of oncoproteins. However, the risk factors and clinical patterns of postoperative recurrence among patients with completely resected EGFR-mutant NSCLC have not been fully understood. Moreover, the prognostic values of routinely used immunohistochemical (IHC) markers in NSCLC are seldom reported.
Method
Consecutive patients with curative resected NSCLC and confirmed EGFR mutations at Fudan University Shanghai Cancer Center from January 2007 to December 2017, were retrospectively enrolled. The initial recurrence sites were recorded and categorized into five groups: thoracic recurrence, brain recurrence, neck recurrence, abdominal recurrence, and bone recurrence. The indicators of overall and site-specific recurrence were identified using the Cox regression model, where a panel of routinely used IHC markers (including Her2, Ki67, TTF-1, CK20, CK7, CK5/6, p53, RRM1, NapsinA, p40, syn, Bcl-2, CDX2, ERCC1 and p63) were incorporated. A nomogram was developed based on variables selected in multivariate analysis. The bootstrapping method (1000 repetitions) was applied to internally validate the nomogram
Result
After a median follow-up of 32 (range, 5-122) months, disease recurrence was observed in 197(37.1%) out of the 531 patients, with a median recurrence-free survival (RFS) of 19 (95% CI, 16.63-21.37) months. Most patients (n=136; 69.0%) had thoracic recurrence, followed by brain recurrence (n=41; 20.8%), bone recurrence (n=41; 20.8%), abdominal recurrence (n=14; 7.1%), and neck recurrence (n=13; 6.6%). Sex, tumor size, Ki67, and N stage were independent indicators of thoracic recurrence. Tumor size, N stage, CK20, and Syn were independent indicators of brain recurrence. N stage and Ki67 were independent indicators of bone recurrence. N stage was the independent indicator of abdominal recurrence and neck recurrence. Tumor size, Ki67, CK20, and N stage were independently associated with overall recurrence, and thus a nomogram predicting the 1-, 2-, and 3-year RFS probability was developed based on these four factors. The concordance index (C-index) was 0.723 (95% confidence interval, 0.675 to 0.771) and the calibration curves displayed good agreement between the predicted RFS and the actual observation.
Conclusion
Independent prognostic indicators based on clinic-pathological parameters and routinely used IHC markers were identified to predict overall and site-specific recurrence, which may help to identify optimal candidates for adjuvant therapies and design individualized surveillance strategies among patients with completely resected EGFR-positive NSCLC
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P1.09 - Pathology (ID 173)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.09-05 - ALK Testing in Chinese Advanced NSCLC Patients: A National-Wide Multicenter Prospective Real-World Data Study (The RATICAL Study) (ID 1800)
09:45 - 18:00 | Author(s): Yuan Li
- Abstract
Background
ALK-tyrosine kinase inhibitors increase ORR and PFS times in ALK-fusion positive NSCLC patients. It is therefore crucial to assess the efficacy of different methods for detecting ALK rearrangement. At present, there are most testing methods approved by cFDA to detect ALK rearrangement in China. However, many issues regarding to the procedure and quality control (QC) data of ALK testing in the routine clinical practice is still to be studied. This study is to evaluate the ALK testing platforms, testing procedures, result interpretation quality control and clinicopathological characteristics of ALK positive patients in the real world for Chinese lung cancer patients, and achieve expert consensus on the clinical practice of ALK testing.
Method
Top 31 hospitals with lung cancer patients in China will participate in the study. All advanced NSCLC subjects who received ALK gene test and all ALK positive NSCLC patients who received surgical treatment from Oct. 2018 to Dec. 2019 will be enrolled. The testing platforms include IHC-Ventana，FISH，RT-PCR and NGS. It is expected to enroll a total of 30,000 cases, and the clinicopathological information of the patients will be collected. Ring study and interpretation training will be conducted before the study initiated. When 2,000 and 10,000 cases are enrolled, the interim summary and quality control will be conducted respectively. The results were the interim summary and quality control results of 2,000 cases.
Result
The 2263 enrollees (mean age, 63 years) included 1365 males (60.32%) and 907 females (39.68%). 205 (of 2263, 9.06%) cases were ALK positive. The ALK positive rate of females (11.10%) was significantly higher than that of males (7.74%). The ALK positive rate of non-smoking patients (11.54%) was significantly higher than that of smoking patients (5.70%). In addition to ALK, the positive rate of EGFR, KRAS, ROS1, HER2, MET, RET and BRAF gene alterations was 46.05%, 9.52%, 3.13%, 3.09%, 2.98%, 2.12% and 0.94%, respectively. Total rate of all driver gene mutation was 60.37% in males, while it was 91.71% in female. Total rate of all driver gene mutation was 59.77% in smoking patients and 90.44% in non-smoking patients. Concurrent mutation of ALK with EGFR, KRAS or ROS1 was 0.33%, 0.45% and 0.22%, respectively. The fusion of EML4-ALK accounted for 75%. The inconsistency rate of IHC-Ventana with FISH, RT-PCR, NGS was 95.07%, 91.30% and 95.45%, respectively. For ALK IHC quality control, 109 slides were used for ring study, and 31 pathologists participated in the interpretion. Among 60 negative cases, 25 cases (41.7%) were diagnosed as positive (false positive) by at least one pathologist. Among 49 positive cases, 12 cases (24.5%) were diagnosed as negative (false negative) by at least one pathologist; 34 cases (31.2%) were diagnosed as inconclusive by at least one pathologist. There were 3.5% and 1.1% of cases found to be misinterpreted during the internal QC and regional QC, respectively.
Conclusion
NSCLC patients harboring ALK gene translocation have unique clinicopathological characteristics. Some problems will still be encountered in the real world clinical practice of ALK testing, which need to be guided by establishment of expert consensus.
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P1.13 - Staging (ID 181)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Staging
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.13-03 - Lung Adenocarcinomas Manifesting as Radiological Part-Solid Nodules Define a Special Clinical Subtype (ID 35)
09:45 - 18:00 | Author(s): Yuan Li
- Abstract
Background
According to guidelines from the Fleischner Society in 2017, subsolid nodules are categorized into pure ground glass nodules (pGGNs) having only a GGO component and part-solid nodules having both GGO and solid components on thin-section computed tomography (TS-CT). Persistent part-solid nodules with solid components ≥ 6mm should be considered highly suspicious.Clinicopathologic features and prognostic predictors of radiological part-solid lung adenocarcinomas were unclear.
Method
We retrospectively compared clinicopathologic features and survivals of part-solid tumors with those of pure ground glass nodules (pGGNs) and pure solid tumors receiving surgery at Fudan University Shanghai Cancer Center, and evaluated prognostic implications of consolidation-to-tumor ratio (CTR), solid component size and tumor size for part-solid lung adenocarcinomas.
Result
911 patients and 988 pulmonary nodules (including 329 part-solid nodules (PSNs), 501 pGGNs & 158 pure solid nodules) were analyzed. More female patients (P=0.015) and non-smokers (P=0.003) were seen in PSNs than those in pure solid nodules. Prevalence of lymphatic metastasis was lower in PSNs than that in pure solid tumors (2.2% vs 27%, P=0.000). 5-year lung cancer specific recurrence free survival (LCS-RFS) and overall survival (OS) of PSNs were worse than those of pGGNs (P<0.001; P=0.042), but better than those of pure solid tumors (P<0.001; P<0.0001), respectively. CTR (OR: 12.90; 95% CI: 1.85-90.04), solid component size (OR: 1.45; 95% CI: 1.28-1.64) and tumor size (OR: 1.23; 95% CI: 1.15-1.31) could predict pathologic invasive adenocarcinoma for PSNs. None of them could predict the prognosis. Patients receiving sublobar resection had comparable prognoses with those receiving lobectomy (5-year LCS-RFS: P=0.178; 5-year LCS-OS: P=0.319). Prognostic differences between patients with systemic lymph node dissection (sLND) and those without sLND were statistically insignificant.
ConclusionTable1 Baseline clinicopathologic characteristics of objects in this study All
N=988Part Solid nodule
N=329Pure Ground Glass nodule
N=501Pure Solid nodule
N=158P value Age (Mean±SD) 56.49±10.83 58.89±9.71 53.64±10.86 60.54±10.52 0.000 Gender 0.015 Male 277(30.4) 91 (28.9) 124 (28.2) 62 (39.5) Female 634(69.6) 224 (71.1) 315 (71.8) 95 (60.5) Smoking status 0.003 Smoker 153(16.8) 52 (16.5) 62(14.1) 39(24.8) Non-smoker 758(83.2) 263(83.5) 377(85.9) 118(75.2) Tumor size(mm) 15.14±7.38 20.51±7.18 10.22±3.84 19.54±5.58 0.000 Location 0.009 RUL 364 (36.8) 126 (38.3) 197 (39.3) 41 (25.9) RML 67 (6.8) 21 (6.4) 29 (5.8) 17 (10.7) RLL 181 (18.3) 48(14.6) 93 (18.6) 40 (25.3) LUL 266 (26.9) 98 (29.8) 130 (25.9) 38 (24) LLL 110 (11.2) 36 (10.9) 52 (10.4 ) 22 (14.1) Surgery 0.000 Wedge resection 456(46.2) 72(21.9) 370(73.8) 14(8.9) Segmentectomy 97(9.8) 33(10.0) 58(11.6) 6(3.8) Lobectomy 435(44.0) 224(68.1) 73(14.6) 138(87.3) Pathology 0.000 AIS/MIA 509(51.5) 56(17.0) 447(89.2) 6(3.8) IAD 479(48.5) 273(83.0) 54(10.8) 152(96.2) Lepidic predominant 154(32.6) 104(38.8) 30(55.5) 30(55.5) 0.000 Solid/Micropapillary predominant 21(4.5) 4(1.5) 1(1.9) 16(3.4) 0.000 Acinar/Papillary predominant 290(61.4) 157(58.6) 22(40.7) 111(74.0) 0.000 Mucinous adenocarcinoma 7(1.5) 3(1.1) 1(1.9) 3(2.0) 0.753 Pathologic N status 0.000 N0 904 (94.9) 305(97.8) 488 (100) 111(73) N1/2 48(5.1) 7(2.2) 0 (0) 41 (27)
Part-solid lung adenocarcinoma showed different clinicopathologic features compared with pure solid tumor. CTR, solid component size and tumor size could not predict the prognosis. Part-solid lung adenocarcinomas define one special clinical subtype.
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P1.17 - Treatment of Early Stage/Localized Disease (ID 188)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.17-15 - Risk, Pattern and Outcome of Brain Metastases in Completely Resected Stage I (AJCC 8th Edition) Non-Squamous Non-Small Cell Lung Cancer (Now Available) (ID 1007)
09:45 - 18:00 | Author(s): Yuan Li
- Abstract
Background
Brain as the first site of recurrence after complete resection in stage I non-squamous non-small cell lung cancer (NSCLC) is occasionally encountered. However, the risk factors and clinical outcomes of this uncommon situation are not fully understood.
Method
The records of patients who underwent curative surgery at Fudan University Shanghai Cancer Center were reviewed and two cohorts with stage I non-squamous NSCLC were identified. The training cohort consisted of randomly selected patients from January 2013 to December 2017. The validation cohort included consecutive patients from January 2011 to December 2012. Brain metastasis free survival (BMFS) were calculated from the time of surgery to the documentation of brain metastasis (BM). Overall survival (OS) was measured from the documentation of BM to the time of any cause of death. A nomogram was developed based on variables selected in multivariate analysis.
Result
With a median follow-up of 28 (range, 10-69) months, 16 of the 596 patients in the training cohort had its initial relapse in the brain. The 1-year, 2-year, and 3-year cumulative incidence of BM were 0.7%, 1.9% and 4.2%, respectively. Tumor size≥2cm (HR=5.09, p=0.024), visceral pleural invasion (HR=2.79, p=0.007), expression of Syn (HR=4.24, p=0.007) and expression of CK20 (HR=14.01, p<0.001) were independent risk factors of BM. Afterwards, a nomogram predicting BMFS was developed based on these four factors. Of note, EGFR mutation was not associated with BMFS. Additionally, with a median follow-up of 75 (range, 7-98) months, 18 of the 478 patients in the validation cohort had its initial recurrence in the brain. The nomogram was validated with a concordance index of 0.93 (95%CI, 0.88-0.98) and the calibration curves displayed good agreement between the predicted BMFS and the actual observation. Among the 34 patients with BM, 10 also had extracranial recurrence, 7 were symptomatic and 24 had oligo-metastases in the brain. By the time of data cut-off, 14 patients died with a 5-year OS rate of 24.8%. Positive expression of Syn or CK20 was significantly associated with reduced OS, while upfront local therapy (surgery and/or radiotherapy) after detection of BM tended to prolong OS (p=0.068).
Conclusion
Positive expression of Syn and CK20, but not EGFR mutation, were independent risk factors of BM and reduced survival in curative resected stage I non-squamous NSCLC. The majority of patients developing BM were asymptomatic and initially having oligo-metastases, highlighting the importance of regular brain imaging for patients with high risks.
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P2.11 - Screening and Early Detection (ID 178)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.11-14 - Evolutionary Action Score of TP53 Predicts the Prognosis of Patients with Stage I Lung Adenocarcinoma (ID 53)
10:15 - 18:15 | Author(s): Yuan Li
- Abstract
Background
Several studies have reported that TP53 mutations were associated with poor prognoses for patients with non-small-cell lung cancer. TP53 was reported to have a mutation rate of 46% in lung adenocarcinoma patients. Whether these mutations are of the same prognostic value is questionable. Here we use an algorithm named Evolutionary Action of TP53 (EAp53) which stratifies TP53 missense mutations into high-risk and low-risk groups based on the scores calculated to see whether different types of TP53 mutations are of prognostic value for patients with stage I lung adenocarcinoma.
Method
Whole-exome sequencing was performed on 83 patients who underwent surgery and with a pathologically confirmed adenocarcinoma between January 2011 and August 2013 at Fudan University Shanghai Cancer Center. No patient underwent neoadjuvant therapy. Missense TP53 mutations were classified to low-risk and high-risk groups according to their EAp53 score, which assesses the genotype-phenotype perturbation of point mutations. Patients were divided into 4 groups based on TP53 mutational status: wild-type TP53, truncating mutations, including frame-shift mutations, nonsense mutations, small indels, and splice-site mutations; high-risk missense mutations, defined as missense mutations with an EAp53 score >75.00; low-risk missense mutations, defined as missense mutations with an EAp53 score ≤75.00.
Result
Mutations of major driver genes, tumor suppressor genes and genes of interest for lung adenocarcinoma, including EGFR (60%), TP53 (35%), RB1 (7%), RBM10 (5%), NF1 (4%), CDKN2A (2%), ERBB2 (2%), KRAS (2%), PIK3CA (2%), SMARCA4 (2%), APC (1%), BRAF (1%), KEAP1 (1%) and STK11 (1%) were identified in our cohort of 83 stage I lung adenocarcinoma patients (fig 1a).
TP53 mutations were identified in 29 patients (35%), with 11 high-risk, 9 low-risk, and 11 truncating mutations. Compared with patients with wild-type TP53, patients with TP53 mutations had a significantly lower tumor mutational burden (p < 0.001, fig 1b). Furthermore, there was a significant difference between the wild-type/low-risk group and the truncating/high-risk group (p < 0.001, fig 1b).
Compared with the low-risk group, the high-risk group had significantly worse recurrence-free survival (p = 0.046), while there was no significant difference between the low-risk group and the wild-type group (p = 0.695, figure 1c). Moreover, when we combined the groups into a high-risk/truncating group and a low-risk/wild-type group, the high-risk/truncating group had a significantly worse recurrence-free survival (p = 0.0081, figure 3c) and overall survival (p = 0.0029, figure 1c).
Conclusion
TP53 mutational type is of prognostic value for patients with stage I lung adenocarcinoma.
