Browsing Over 443 Presentations
PDL1: To test or not to test?
- K. Kerr (Aberdeen, United Kingdom)
- K. Kerr (Aberdeen, United Kingdom)
110O - Plasma circulating tumor DNA analysis (ctDNA) for molecular alteration detection in advanced non-small cell lung cancer (NSCLC) patients (pts) with isolated central nervous system (CNS) metastases (mts)
- M. Aldea (Villejuif, France)
- M. Aldea (Villejuif, France)
- L. Hendriks (Maastricht, Netherlands)
- L. Mezquita (Villejuif, France)
- J. Remon-Masip (Barcelona, Spain)
- D. Planchard (Villejuif, France)
- C. Jovelet (Villejuif, France)
- J. Benitez (Barcelona, Spain)
- A. Gazzah (Villejuif, France)
- C. Naltet (Villejuif, France)
- P. Lavaud (Villejuif, France)
- L. Lacroix (Villejuif, France)
- K. Howarth (Cambridge, United Kingdom)
- C. Morris (Cambridge, United Kingdom)
- E. Green (Cambridge, United Kingdom)
- C. Nicotra (Villejuif, France)
- B. Besse (Villejuif, CEDEX, France)
Abstract
Background
In advanced NSCLC, ctDNA is an emerging tool in molecular profile testing at diagnosis and at resistance to targeted therapies. However, for CNS limited mts, ctDNA might have a reduced accuracy because of low concentrations. Aim: to assess feasibility of ctDNA in NSCLC with isolated CNS disease/progression (PD) (iCNS).
Methods
This is a retrospective analysis of consecutive advanced NSCLC pts treated at Gustave Roussy from 01.2016 to 06.2018 included in 2 prospective studies (CEC-CTC, MSN). Included: any molecular tissue alteration at baseline (EGFR, ALK, BRAF, KRAS, HER2, ROS1, MET, TP53), CNS disease and ≥1 ctDNA sample at diagnosis/PD. CtDNA was performed by next generation sequencing (NGS- InVisionSeq™-Lung). Clinical/molecular/imaging data were collected. CtDNA in iCNS group were compared to systemic PD group (with CNS PD or stable disease, S-CNS). ctDNA was defined as positive if ≥ 1 mutation in the NGS panel.
Results
422/959 screened pts had ≥1 ctDNA sample. 183/422 pts had CNS disease. 58/182 pts had ctDNA sample at time of CNS disease and 66 samples were eligible for inclusion: 21 iCNS and 45 S-CNS (≥1 sample/patient as ≥ 1 PD). In iCNS and S-CNS, pts characteristics were: median age 55 vs 59 years, female gender 94% vs 59%, adenocarcinoma histology 100% vs 93%, smoking history 35% vs 44%, median mts sites at diagnosis 1 vs 2. Prevalence of EGFR mutation at diagnosis was 76 and 61%, ALK rearrangement 18 and 10%, KRAS 6 and 5% in iCNS and in S-CNS, respectively. HER2, TP53, BRAF and MET alterations were present only in S-CNS group (12%, 10%, 5% and 2%). CtDNA was positive in 38% in iCNS vs. 98% in S-CNS groups (Fisher test, p < 0.0001) (Table).
Conclusions
In NSCLC pts with isolated CNS involvement, genomic alterations assessed by ctDNA in plasma had a low detection rate. (Table).
Legal entity responsible for the study
Gustave Roussy Institute, Villejuif, France.
Funding
Has not received any funding.
Disclosure
L. Mezquita: Consulting, advisory role: Roche Diagnostics; Lectures, educational activities: Bristol-Myers Squibb, Tecnofarma, Roche, AstraZeneca; Travel, accommodations, expenses: Chugai. D. Planchard: Consulting, advisory role or lectures: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Clinical trials research: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo. C. Morris, E. Green: Employee, shareholder: Inivata. B. Besse: Sponsored research at Gustave Roussy Cancer Center: AbbVie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma; Investigator or co-investigator of trials: Nerviano, GSK, Pfizer, Roche-Genentech, Lilly, OSE Pharma, MSD, Celgene, Stemcentrx, Ignyta, AbbVie, Loxo Oncology, AstraZeneca, Blueprint Medicines. All other authors have declared no conflicts of interest.
Invited Discussant 102O and 103O_PR
- S. Popat (London, United Kingdom)
- S. Popat (London, United Kingdom)
Q&A
77P - The prognostic impact of the international association for the study of lung cancer (IASLC) definitions on completeness of surgical resection for non-small cell lung cancer (NSCLC)
- M. Gagliasso (Cuneo, Italy)
- M. Gagliasso (Cuneo, Italy)
- C. Cartia (Orbassano, Italy)
- A. Maraschi (Orbassano, Italy)
- R. Rapanà (Orbassano, Italy)
- S. Sobrero (Orbassano, Italy)
- A. Sandri (Orbassano, Italy)
- G. Migliaretti (Orbassano, Italy)
- F. Ardissone (Orbassano, Italy)
Abstract
Background
To reappraise the prognostic significance of the IASLC definitions of complete, uncertain, and incomplete resection in NSCLC surgery.
Methods
Single-institution retrospective review of 1052 consecutive patients surgically treated for NSCLC between 2008 and 2017. Complete resection was defined by absence of residual disease; systematic nodal dissection; no extracapsular extension in lymph nodes removed separately or those at lung specimen margin; negativity of distal mediastinal lymph nodes. An uncertain resection was defined by free resection margins, but one of the following applied: inadequate lymph node assessment; positivity of distal mediastinal lymph nodes; presence of carcinoma in situ at bronchial margin; positive pleural lavage cytology. A resection was defined incomplete by presence of residual disease; extracapsular extension in distal mediastinal lymph nodes or those at lung specimen margin; positive cytology of pleural or pericardial effusions. Follow-up was complete and overall survival (OS) was assessed using the Kaplan-Meier method and Cox proportional hazard modeling.
Results
Eight hundred eighty-six (84.2%) patients had a complete resection, 131 (12.5%) an uncertain resection, and 35 (3.3%) an incomplete resection. Median follow-up was 44.9 months (range, 0.1 to 132.3). Complete resection was associated with significantly better survival compared to uncertain and incomplete resection (adjusted hazard ratio, 1.84 and 2.31, respectively; both p = 0.0001). Median OS and 5-year survival rate were 102.3, 32.9, 23.3 months and 62.3%, 33.5%, 24.3% in patients undergoing complete, uncertain, and incomplete resection, respectively. Additional significant predictors for OS in the multivariable Cox model were patient age and Charlson Comorbidity Index; tumor diameter, histology and pathologic TNM stage; and the occurrence of postoperative adverse events.
Conclusions
Our current experience confirms that in NSCLC surgery, significant differences exist in long-term survival following complete, uncertain, and incomplete resection, as defined by the IASLC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Oligometastatic NSCLC
- F. Mornex (Pierre Bénite, France)
- F. Mornex (Pierre Bénite, France)
Patient reported-outcomes: Where nursing fits
- C. Diez de los Rios de la Serna (Southampton, United Kingdom)
- C. Diez de los Rios de la Serna (Southampton, United Kingdom)
Biomarkers for I-O
- L. Bubendorf (Basel, Switzerland)
- L. Bubendorf (Basel, Switzerland)
197P - Effect of surgical treatment on the survival in patients with malignant pleural mesothelioma
- R. Baez-Saldana (Ciudad de México, Mexico)
- R. Baez-Saldana (Ciudad de México, Mexico)
- M. Marmolejo-Torres (Mexico City, Mexico)
- M. Iñiguez-García (Mexico City, Mexico)
- J. Berrios Mejía (Mexico City, Mexico)
- U. Rumbo-Nava (Mexico City, Mexico)
- O. Arrieta-Rodríguez (Mexico City, Mexico)
Abstract
Background
In patients with malignant pleural mesothelioma (MPM) chemotherapy is the only treatment modality that has been shown to improve survival. Surgery, by either pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP) can be an option of treatment in patients with early stage disease and good functional status, nevertheless, this modality remains questionable. The aim of this study was to evaluate the effect of surgical treatment on the survival in patients with MPM.
Methods
Case series of patients with histologically proven MPM between January 2012 and Jun 2015 were reviewed retrospectively. The variables analyzed were: age, sex, asbestos exposure, smoking history, biomass exposure, performance status with ECOG scale, staging and type of treatment. Univariate and multivarite analyses were performed using the Cox regression model. Survival functions were estimated using the Kaplan-Meier statistics. The decision to perform either P/D or EPP was on the basis surgeon’s preference.
Results
There were 122 cases of MPM; 71% were males and the media age at diagnosis was 63 years. Twenty (16.4%) of the cases received surgery, 8 EPP, 8 P/D, and 4 were unresectable at the moment of the surgery. The 30-day mortality was 5%, one patient after EPP. The median survival in all cases was 8.6 months, while in the surgical vs no surgical group was 15.8 vs 7.2 months respectively (p < 0.05). In comparision to no surgery treatment, surgery alone was associated with significant improvement in survival [adj HR 0.20 (95%CI: 0.07-0.56). At multivariate analysis independent significant predictors of survival were surgery [adj HR 0.21 (95%CI: 0.06-0.71), beign female [adj HR 0.49 (95%CI: 1.06-4.48), chemotherapy [adj HR 0.22 (95%CI: 0.07-0.70), stage early vs advanced [adj HR 0.47 (95%CI: 0.22-1.04) and ECOG < 2 [adj HR 0.21 (95%CI: 0.06-0.76).
Conclusions
Our data suggest relative advantage of surgery on survival. Patients who received surgery had better survival than patients who were treated with chemotherapy or palliative care alone.
Legal entity responsible for the study
Instituto Nacional de Enfermedades Respiratorias.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Epidemiology and asbestos ban: European picture
- L. Greillier (Marseille, France)
- L. Greillier (Marseille, France)
168P - Dynamic changes of patelet-to-lymphocyte ratio predict efficacy of PD-1/PD-L1 inhibitors in NSCLC
- F. Zhou (Shanghai, China)
- F. Zhou (Shanghai, China)
- A. Xiong (Shanghai, China)
- C. Zhou (Shanghai, China)
Abstract
Background
Baseline neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of host inflammation and have been reported as prognostic factors in advanced cancer patients, but have not been analyzed extensively in lung cancer in the era of immunotherapy, especially the dynamic changes of these markers.
Methods
Patients who were treated with immune checkpoint inhibitors (ICIs) either as a standard of care or on a clinical trial at Shanghai Pulmonary Hospital were enrolled. Baseline complete blood count [defined as the results obtained at the time (−3/0 days) of initiating ICIs, including white blood cell (WBC), absolute neutrophil count (ANC), platelet count and absolute lymphocyte count (ALC) to calculate the NLR and PLR] were extracted from medical records. Derived NLR (dNLR) was calculated as dNLR = ANC/(WBC−ALC). C3 complete blood count (defined as the results obtained before Cycle 3 of ICIs) was also collected and calculated.
Results
Ninety-five patients were identified in the present study. 49 (51.6%) of patients received ICI monotherapy, and 46 (48.4%) received ICI-based combination therapy. Baseline NLR, dNLR, PLR were not associated with clinical outcomes of ICI therapy (ORR or PFS). Using 5 as a C3 NLR cut-off value, patients with C3 NLR <5 had better ORR and PFS than those with C3 NLR ≥5. Furthermore, patients who had increased NLR (n = 29) had inferior ORR (17.2% versus 41.0%, P = 0.026) and median PFS (5.5 versus 8.5 months, P = 0.022) than those who had decreased NLR (n = 61). Patients with C3 dNLR <3 had better ORR and median PFS than those with C3 dNLR ≥3. Patients who had increased dNLR (n = 26) had lower ORR (15.4% versus 40.3%, P = 0.027) and inferior median PFS (5.6 versus 8.4 months, P = 0.150) than those who had decreased dNLR. There was a trend towards better ORR and median PFS in patients lower C3 PLR. Interestingly, patients who had decreased PLR (n = 47) had better ORR (42.6% versus 23.3%, P = 0.052) and median PFS (11.8 versus 5.5 months, P = 0.003) than those who had increased PLR (n = 43). Multivariate analysis revealed dynamic changes of PLR as an independent predictive factor for PFS (HR: 2.27, 95% CI, 1.10-4.71, P = 0.027).
Conclusions
Dynamic change of PLR has a potentially predictive role of the efficacy of ICI therapy.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
12P - Clinicopathologic characteristics of patients with TP63 mutations in Chinese non-small cell lung cancer
- Q. Zhang (Fuzhou, China)
- Q. Zhang (Fuzhou, China)
- C. Xu (Fuzhou, China)
- W. Wang (Zhenjiang, China)
- W. Zhuang (Fuzhou, China)
- Z. Huang (Fuzhou, China)
- G. Chen (Fuzhou, China)
- M. Fang (Zhenjiang, China)
- T. Lv (Nanjing, China)
- Y. Song (Nanjing, China)
Abstract
Background
Variation at TP63 has recently been shown to be associated with non-small cell lung cancer patients (NSCLC) in the Chinese population. There is some clinical evidence for the use of TP63 mutations as prognostic and predictive biomarker. The aim of this study is to investigate mutations and prognosis of NSCLC harboring TP63 mutations.
Methods
A total of 1236 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of TP63 mutations and other genes were detected by next generation sequencing.
Results
TP63 gene mutation rate was 2.02% (25/1236) in non-small cell lung cancer, including R643* (1 patient), H247N (1 patient), A139V (1 patient), V626F (1 patient), Q70* (1 patient), Q274E (1 patient), H615D (1 patient), R350T (1 patient), Y202Kfs*29 (1 patient), P229H (1 patient), M40V (1 patient), E409Q (1 patient), V179M (1 patient), W658* (1 patient), S365* (1 patient), T193M (1 patient), L50F (1 patient), A554E (1 patient), R226H (1 patient), Q99* (1 patient), S310N (1 patient), T169N (1 patient), R266Q (1 patient), D372H (1 patient), and P492T (1 patient), and median overall survival (OS) for these patients was 15.0 months. Among them, all patients were TP63 gene with co-occurring mutations. Briefly, patients with (n = 5) or without (n = 20) co-occurring EGFR mutations had a median OS of 22.5 months and 14.0 months respectively (P = 0.23); patients with (n = 21) or without (n = 4) co-occurring TP53 mutations had a median OS of 15.0 months and 13.0 months respectively (P = 0.33); patients with (n = 5) or without (n = 20) co-occurring BRAF mutations had a median OS of 14.0 months and 15.0 months respectively (P = 0.72); patients with (n = 5) or without (n = 20) co-occurring KRAS mutations had a median OS of 6.0 months and not up to now respectively (P < 0.01).
Conclusions
TP63 is structurally and functionally similar to TP53 and their activity as transcription factors is regulated by a wide repertoire of shared and unique post-translational modifications and interactions with regulatory cofactors. EGFR, TP53 and BRAF gene accompanied may have less correlation with TP63 mutation in NSCLC patients. KRAS accompanied mutations might play a worse prognosis in TP63 gene mutation NSCLC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.