Contralateral Lung Metastasis Research Articles

Lung adenocarcinomas with mucinous histology: clinical, genomic, and immune microenvironment characterization and outcomes to immunotherapy-based treatments and KRASG12C inhibitors

BackgroundApproximately 10% of lung adenocarcinomas (LUAD) have mucinous histology (LUADMuc), which is associated to a light/absent smoking history and a high prevalence of KRAS mutations. We sought to characterize LUADMuc by comparing it to LUAD without mucinous histology (LUADnon-muc) and determine the relative benefit of current treatments. Patients and MethodsPatients with LUAD from five institutions and TCGA PanCancer Atlas classified as LUADMuc or LUADnon-muc were included. Clinicopathologic, genomic, immunophenotypic, transcriptional features, and treatment outcomes were compared between LUADMuc and LUADnon-muc. ResultsOf 4,082 patients with LUAD, 9.9% had LUADMuc. Compared to LUADnon-muc, patients with LUADMuc had a lighter smoking history (median: 15 vs 20 pack-years, P=0.008), lower PD-L1 TPS (median: 0% vs 5%, P<0.0001), and lower tumor mutation burden (median: 6.8 vs 8.5 mutations/megabase, P<0.0001). Mutations in KRAS, NKX2-1 (TTF-1), STK11, SMARCA4, GNAS, and ALK rearrangements were enriched in LUADMuc, while TP53, EGFR, BRAF, and MET mutations were enriched in LUADnon-muc. At stage IV diagnosis, LUADMuc was more likely to have contralateral lung metastasis (55.2% vs 36.9%, P<0.0001) and less likely to have brain metastases (23.3% vs 41.9%, P<0.0001). Compared to LUADnon-muc, LUADMuc cases showed lower intratumor CD8+, PD-1+, CD8+PD-1+, and FOXP3+ cells. Among metastatic cases receiving ICIs, compared to LUADnon-muc (N=1,511), LUADMuc (N=112) had lower objective response rate (ORR, 8.4% vs 25.9%, P<0.0001), and shorter median progression-free survival (mPFS, 2.6 vs 3.9 months, P<0.0001) and overall survival (mOS, 9.9 vs 17.2 months, P<0.0001). Similarly, patients with LUADMuc had worse outcomes to chemo-immunotherapy. LUADMuc (N=18) and LUADnon-muc (N=150) had similar ORR (16.7% vs 34.9%, P=0.12) and mPFS (4.6 vs 5.6 months, P=0.17) to treatment with KRASG12C inhibitors, but LUADMuc had shorter mOS (6.8 vs 10.8 months, P=0.018). ConclusionLUADMuc represents a distinct LUAD subpopulation with unique clinicopathologic, genomic, immunophenotypic, and transcriptional features, achieving worse outcomes to standard immunotherapy-based treatments.

Immunotherapy and PD-L1 Tumor Expression in Moroccan Non-Small Cell Lung Cancer Patients with Various Metastasis.

The question of whether tumor expression of PD-L1 and the presence of distant metastasis could influence the efficacy of immunotherapy represents a major challenge and needs to be further elucidated. The aim of this study is to evaluate the predictive significance of tumor expression of PD-L1 as well as the number and site of metastasis in non-small cell lung cancer (NSCLC) among Moroccan patients treated with immunotherapy. Between January 2019 and February 2023, we recruited Moroccan patients with metastatic NSCLC. All were treated with immunotherapy, either as monotherapy or in combination with chemotherapy. Immunohistochemistry was used to assess PD-L1 (clone 22C3) and ALK (clone D5F3) status. EGFR status was established by qPCR. Tumor PD-L1 expression was classified into 2 levels: TPS <1% (negative expression) and TPS ≥1% (positive expression). Statistical analysis was performed using SPSS Statistics V.21 software. The median age of patients (N=40) was 67 years (39- 92 years) and the sex ratio was 9. Disease dissemination revealed that 22.5% (N=9) of patients had a metastatic burden ≥ 3 (MB≥3). As for the sites of metastasis, the results showed that 20% (N=8), 10% (N=4), 42.5% (N=17), 22.5% (N=9), 27.5% (N=11), 45% (N=18) and 27.5% (N=11) of patients had developed lymph node, liver, bone, brain, pleural, contralateral lung and adrenal metastasis respectively. Positive PD-L1 expression was significantly associated with shorter overall survival (OS = 17.19 vs. 28.85 months, p=0.01). High metastatic burden (MB ≥ 3) was associated with lower objective response rate (ORR), shorter progression-free survival (PFS), and reduced OS, respectively (ORR = 0 vs. 58.06%, p=0.002; PFS = 10.23 vs. 25.27 months, p=0.001; and OS = 11.60 vs. 27.91 months, p=0.003). Only the presence of osseous metastasis was significantly associated with lower ORR, shorter PFS, and OS compared to other metastatic locations (ORR = 5.88 vs. 73.9%, p=0.000; PFS = 10.72 vs. 31.33 months, p=0.000; and OS = 11.39 vs. 36.17 months, p=0.000). Finally, the presence of hepatic metastasis was significantly associated with shorter PFS (10.75 months) compared to those without hepatic metastasis (22.53 months) (p=0.046). Finally, the results of the multivariate analysis revealed that the presence of bone metastasis was strongly correlated with a significant decrease in progression-free survival (p=0.001) as well as overall survival (p=0.002). Our results suggest that tumor expression of PD-L1 and metastatic burden should play a significant role in predicting the response to immunotherapy. Furthermore, it is important to note that the presence of osseous and hepatic metastasis could negatively influence the clinical outcomes of immunotherapy.

Optimal therapeutic strategy for non-small cell lung cancer with thoracic extrathoracic metastasis: a study based on SEER database.

Non-small cell lung cancer (NSCLC) patients with extrathoracic metastasis (EM) are a highly heterogeneous cohort. Some of these patients could benefit from primary tumor surgery. This study aimed to identify potential NSCLC patients with EM suitable for primary tumor resection and to determine the optimal therapeutic strategy. NSCLC patients with EM were extracted from the Surveillance, Epidemiology and End Results database between 2010 and 2015. They were stratified into subgroups with single and multi-EMs. Cox regression analysis was adopted to identify prognostic factors for overall survival (OS). The Kaplan-Meier method was used to compare the OS among patients who received different treatment modalities. The univariate Cox regression analysis demonstrated that advanced age, male sex, race (black), married status, squamous cell carcinoma, higher histological grade, advanced T or N stage, contralateral lung metastasis, multi-EMs, tumor size >2 cm, and lack of treatment were associated with poorer OS in patients with NSCLC (P<0.05). Multivariate Cox regression analysis revealed that the number of EM and treatment modalities were independent prognostic factors affecting OS (P<0.001). For patients with single EM, those who did not receive treatment and those who underwent single-agent chemotherapy, single-agent surgery, surgery combined with chemotherapy, surgery combined with radiotherapy, or surgery combined with chemoradiotherapy had median OS times of 3.0, 11.0, 12.0, 26.0, 11.0, and 25.0 months, respectively. Compared to monotherapy, combination therapy showed significant benefits for patients with single EM in NSCLC. Furthermore, patients with single EM who underwent lobectomy, bilobectomy, or pneumonectomy had significantly longer survival than those who underwent sublobar resection, even when the primary tumor size was ≤2 cm (P=0.04). Primary tumor surgery could benefit NSCLC patients with single EM; lobectomy was at least warranted to improve survival even for primary tumors with size ≤2 cm.

Actionable mutations in non-small cell lung cancer in patients at hospital de Especialidades Eugenio Espejo, Ecuador 2017-2020.

Determine the frequency of actionable mutations in non-small cell lung cancer (NSCLC) and their correlation with overall survival (OS) and the site of metastases. We performed a descriptive cross-sectional study at the Hospital de Especialidades Eugenio Espejo, Ecuador, between 2017 and 2020. Demographic, pathological, and molecular alterations in epidermal growth factor (EGFR), Anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1), Programmed death-ligand 1 (PD-L1) expression, and clinical data detailed in patients' medical records with metastatic NSCLC were collected and analyzed. Seventy-nine stage IV patients had NSCLC; adenocarcinoma histology represents 56 (70.9%). The predominant mutation was in EGFR (22.8%); the most common variant was the deletion of exon 19 (72.2%). The most common metastatic site was in the contralateral lung (22.3%); however, this variable showed no significant correlation to the molecular markers (p=0.057). The overall survival (OS) and the status of molecular markers are not statistically significant (p=0.27). OS was better for non-mutated EGFR than for mutated EGFR (p=0.012). However, the frequency values are unrelated to contralateral lung metastasis or survival. Our frequency mutations are concordant with those found in other studies in Latin America. EGFR was the most common biomarker mutation, and there was a better OS in EGFR non-mutated patient.

Analysis of non-small cell lung cancer with miliary lung metastasis in patients harboring epidermal growth factor receptor mutations

Miliary lung metastasis is a unique feature of lung metastasis in non-small cell lung cancer (NSCLC), indicating hematogenous dissemination. Some studies reported more frequency of epidermal growth factor receptor (EGFR) mutation and worse prognosis in these patients. Cases were identified from Chi-Mei medical center cancer registry for the period 2015–2019. Inclusion criteria were NSCLC with contra-lateral lung metastasis harboring EGFR mutation, under tyrosine kinase inhibitor (TKI) prescription. Patients with miliary or non-miliary lung metastasis were enrolled for survival analysis. 182 NSCLC patients were enrolled for assessing time to discontinuation of TKI (TD-TKI), progression-free survival (PFS) and overall survival (OS). 54 patients with miliary lung metastasis had average 13.2 months [95% confidence interval (CI) 10.7–15.6] of TD-TKI, 11.4 months (95% CI 9.3–13.6) of PFS, and 21.3 months (95% CI 16.8–25.8) of OS, which were shorter than non-miliary group with marginally statistical significance. In multivariate analysis, miliary lung metastasis had no statistical significance, and other strong prognostic indicators were found including performance status, liver metastasis, EGFR type, and generation of TKI. In NSCLC patients harboring EGRF mutation under TKI prescription, miliary lung metastasis was not a dominant indicator for outcomes evaluation.

Combined SCLC clinical and pathological aspects.

Combined small cell lung carcinoma (C-SCLC) is rare and accounts for 1-3% of all lung cancer cases. Although its incidence has increased recently, there are limited studies on it. The records of patients admitted to our hospital between January 2015 and December 2019 and diagnosed with histologically proven combined small cell were scanned retrospectively and reviewed. 31 patients were analyzed. The average follow-up time was 10 months. The radiotherapy (RT) rate, surgery rate, and large cell malignancy rate were significantly lower in the ex group than in the living group (p=0.024, p=0.023, p=0.015). The rates of extensive disease, metastasis, and thyroid transcription factor 1 (TTF1) were significantly higher in the old group than in the living group (p=0.000, p=0.000, p=0.029, respectively). In the univariate model, sequential RT, fatigue, lactate dehydrogenase (LDH), stage, metastasis, contralateral lung metastasis, chemotherapy were observed to be significantly effective in predicting survival time (p=0.000, p=0.050, p=0.011, p=0.004, p=0.004, p=0.045, p=0.009). In the multivariate model, independent (p=0.015, p=0.022, p=0.049) efficacy of RT, stage, and chemotherapy in predicting survival was observed. C-SCLC is a specific mixed carcinoma and reports evaluating this type are still scarce. The stage of the disease, radiotherapy and chemotherapy are extremely important in predicting survival.

18F-Labeled Fluoro-2-Deoxyglucose Positron Emission Tomography and Computed Tomography in a Large Pulmonary Sclerosing Pneumocytoma with Contralateral Lung Metastasis.

Pulmonary sclerosing pneumocytoma is an exceedingly rare neoplasm of the lung. These tumors are usually slow growing with a benign disease course but can easily be mistaken for carcinoid tumors or adenocarcinoma in cytology or histopathology specimens. Rare occurrences of metastases have been reported in the literature making 18F-labeled fluoro-2-deoxyglucose positron emission tomography and computed tomography useful for the evaluation of these tumors.

P52.12 Incidence of Brain Metastasis in Advanced Non-Small Cell Lung Cancer at Presentation-An Experience From Tertiary Care Centre in South India

Brain metastasis is one of the most significant problems in patients with lung cancer. Many patients with brain metastasis are asymptomatic at presentation.Due to its prognostic significance and bad survival, many studies looked upon the incidence of brain metastasis at the presentation of NSCLC. Most of them are retrospective studies conductedin different parts of the world. To the best of our knowledge, the frequency of brain metastasis in patients with NSCLC at initial presentation in India has not been studied.So we planned a study to evaluate the incidence of brain metastasis in NSCLC patients treated in our center. It is a prospective observational study conducted in the department of medical oncology at our tertiary care center from Sep 2019- March 2020. A total of 80 patients with lung cancer were registered in the department. Among them,66 patients had advanced non- small cell carcinoma of the lung (NSCLC),and they were enrolled in the study.Clinical profile,performance status, demographic characteristics, smoking history, and imaging findings were noted at the time of presentation. MRI brain was taken for all advanced NSCLC patients,and the results were analyzed. . Mean age at presentation was 60 years. 20(30%) patients were smokers and 46(70%) were non-smokersAmong 66 patients, 33% had brain metastasis. 15 (63%) patients were adenocarcinoma, whereas 9 (27%) patients had squamous cell carcinoma. 42% had asymptomatic brain metastasis at presentation. All patients with brain metastasis received radiotherapy. Other parameters are tabulated as follows.Tabled 1Baseline CharacteristicsParametersNo of Patients (%)Mean Age60 yearsMale36 (54%)Female30 (46%)ECOG0-256 (85%)310 (15%)Brain Metastasis24 (33%)Male10 (42%)Female14 (58%)Adenocarcinoma15 (63%)Squamous Cell Carcinoma9 (37%)Asymptomatic14 (58%)Symptomatic10 (42%)Hemorrhagic5 (21%)Non-hemorrhagic19 (79%)Synchronous metastasis12 (18%)Contralateral Lung Metastasis6 (9%)Liver4 (6%)Bone2 (3%) Open table in a new tab Our study has found that incidence of brain metastasis is higher in South India when compared to western data. The other findings include female patients had slightly higher predilection for brain metastasis. Adenocarcinoma histology and synchronous contralateral lung metastasis are common in patients with brain metastasis. There are no validated biomarkers to predict brain metastasis in NSCLC due to its molecular heterogeneity. As the study was conducted in resources limited setting molecular correlation in patients with brain metastasis was not done. The study will serve as a baseline platform of clinical predictors of brain metastasis in NSCLC. Our future direction and research will be clinical predictors along with molecular driver mutations in NSCLC in detecting brain metastasis

Abstract B32: Silencing of oncogenic KRAS by a mutant-favoring short interfering RNA

Abstract Oncogenic mutations in the KRAS gene are well-established drivers of cancer. Promising preclinical strategies including RNA interference (RNAi) have been developed to target oncogenic KRAS function, yet a clinically effective therapy to directly target KRAS remains to be achieved. While genetic knockdown of mutant KRAS (mKRAS) with RNAi is one promising approach, current methods are not mutant-selective, and thus they also decrease normal KRAS levels, raising concerns about normal cell toxicity. Here, we describe a custom short interfering RNA (siRNA) oligonucleotide (D1) designed to preferentially bind the most commonly occurring RAS missense mutations in codons 12 and 13. Our approach designed the siRNA to have three mismatches binding wild-type mRNA, but only two mismatches for the oncogenic mRNAs, thus having binding affinities more favorable for the mutant-specific sequences. Using NIH/3T3 mouse fibroblasts stably expressing human KRAS WT or mutant cDNA sequences and KRAS mutant lung cancer cell lines, we determined that D1 siRNA preferentially reduced mKRAS mRNAs versus the wild-type sequence at the transcriptional and protein levels. Phenotypically, D1 siRNA significantly reversed mKRAS-induced morphologic and growth transformation of NIH/3T3 cells. Furthermore, D1 siRNA significantly impaired the proliferation of several mKRAS lung cancer cells in 2D as well as 3D spheroids embedded in an extracellular matrix. To overcome clinical limitations of delivering the siRNA to lung tumors, we evaluated lipid nanoparticles (LNPs) as carriers of D1 siRNAs in orthotopic mKRAS lung cancer models and observed that Cy5.5-labeled LNPs are highly enriched in lung tumors and metastases. Compared with control siRNA-LNP treated mice, 344SQ (KRAS G12D) tumor-bearing mice injected once with D1 siRNA-LNPs had drastically decreased KRAS protein levels in tumors 72 h later (73% decrease, p=0.001). Using an orthotopically injected luciferase-labeled A549 (KRAS G12S) human lung cancer model, D1 siRNA-LNP treated mice had pronounced reductions in luciferase signal (56% reduction, p=0.045), chest wall metastases (67% reduction, p&amp;lt;0.001) and contralateral lung metastases (73% reduction, p&amp;lt;0.01). Interestingly, D1 siRNA-LNP did not impair tumor growth when applied in the 344SQ mKRAS orthotopic mouse lung model, consistent with the mKRAS-independent growth of this line. This result supports our conclusion that the effects of D1 siRNA-LNP in the A549 model are KRAS specific and highlight the importance of determining RAS-dependency a priori for KRAS-targeting therapeutics. Taken together, our data indicate a novel use of RNAi to specifically target oncogenic KRAS-driven cancers. Citation Format: Bjoern Papke, Amanda E.D. Van Swearingen, Anne Y. Feng, Salma H. Azam, Emily B. Harrison, Runying Yang, Adrienne D. Cox, Channing J. Der, Chad V. Pecot. Silencing of oncogenic KRAS by a mutant-favoring short interfering RNA [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr B32.

Microwave ablation for non-small cell lung cancer with synchronous solitary extracranial metastasis.

Local therapy including surgery or radiotherapy has been reported for the treatment of non-small cell lung cancer (NSCLC) with synchronous solitary metastasis, while studies with other local ablative treatment are rare. Here, we summarized our single-center experience of microwave ablation (MWA) for both primary and metastatic lesions in NSCLC patients with synchronous solitary extracranial metastases. We retrospectively screened our institute database from January 2014 to Jun 2019. NSCLC patients with synchronous extracranial solitary metastasis with primary and metastatic lesions that were treated with MWA were identified and analyzed. Of the 1472 stage IV NSCLC patients found, 38 were diagnosed with synchronous extracranial solitary metastasis and 29 of them received MWA for primary and metastatic lesions. The most common distant metastases were contralateral lung metastases (14 cases), followed by bone (6), liver (4), adrenal gland (3) and pleura metastases (1). Median OS and PFS was 21.5 and 12.5months, respectively. Patients with N0 had significantly longer PFS (median 18.5 vs. 8.0months) and OS (median 42.7 vs. 19.0months). In addition, systemic therapy was showed to be a prognostic factor for better PFS (12.9 vs. 7.5months). Clinical pathological factors including age, histology, T stage, PS score, and metastasis locations are not significantly associated with survival. MWA may serve as an alternative treatment for NSCLCs with synchronous solitary extracranial metastases.

P2.15-07 Bimanual Examination Is Indispensable in the Surgery of Lung Metastatic Tumors!

Thoracic computed tomography (Th CT) is used to evaluate the surgical outcome of lung metastatic tumors. However, Th CT is often inadequate on the detection of millimetric lesions and it alone is a problematic for guiding complete resection. It is recommended for complete resection that the intraoperative bimanual palpation of the lung to be used with care and meticulously. In addition, there are studies for minimally invasive surgical methods may be an alternative to thoracotomy where bimanual evaluation is not possible. In this study, we aimed to evaluate the number of radiological and pathological metastases in patients who underwent metastasectomy with muscle conservative thoracotomy (MCT). Between 2008 and 2018, 204 patients with metastatic lung tumors who underwent metastasectomy were included in the Department of Thoracic Surgery, Ankara University Faculty of Medicine. Preoperative Th CT imaging of all patients was evaluated in a multidisciplinary council. The relationship between the numbers of metastases detected by pathological examination of patients and the number of pulmonary nodules reported as 'metastasis' in preoperative Th CT was retrospectively analyzed. 55% (n: 111) of the patients were F, 45% (n: 93) were M, mean age was 46.4 (13-77). %25 (n:52) of two hundred and four patients had bilateral, 3% (n: 8) of the patients had 3 and 1% (n: 4) of the patients had 4 metastasectomy with MCT due to contralateral lung metastasis or re-metastasectomy. The number of pulmonary nodules detected in Th CT was 740 (mean: 2,6), although the number of pulmonary nodules resected was 1503 (mean: 5,29). In histopathological evaluation of these nodules, 1120 (mean: 3,94) were reported as metastases. 2,03 fold of the nodules detected in Th CT were detected by bimanual intraoperative examination and 1.5 fold of nodules detected in Th CT were pathologically assessed as metastasis. Primary tumor numbers and histologies of 1120 metastatic nodules respectively; 42% (n: 475) were epithelial tumors and 58% (n: 645) were mesenchymal tumors. In this study, 740 pulmonary nodules were reported in Th CT of 204 patients. However, 763 additional pulmonary nodules were detected by bimanual palpation. 49.8% (380/763) of 763 additional pulmonary nodules were metastatic. Although minimally invasive surgery is a successful method for the surgery of many thoracic malignancies, bimanuel palpation of the lung with open surgery is still an effective method for the complete resection of pulmonary metastases. Bimanual examination is indispensable especially in the pulmonary metastasectomy of sarcomas.

91P - Prognosis of EGFR-mutant advanced lung adenocarcinoma patients with different intrathoracic metastatic patterns

Introduction: Lung cancer diagnosed solely with the presence of intrathoracic metastases is classified as M1a. However, intrathoracic metastases can be further divided into different patterns. The objective of our study was to analyze the differences in survival between the different metastatic patterns of intrathoracic metastases in lung adenocarcinoma patients who have epidermal growth factor receptor (EGFR) mutations. Materials and Methods: Patients who were diagnosed only with intrathoracic metastasis between March 2011 and October 2016 and had EGFR-mutations were selected for this study. Prognosis was determined based on metastatic patterns by univariate and multivariate analysis. Results: A total of 137 patients (60 patients who only had pleural metastasis [Group A], 44 patients who only had contralateral lung metastasis [Group B] and 33 patients who had both pleural and contralateral lung metastasis with or without pericardial effusion [Group C]) were selected for this in the study. The median OS (overall survival) time was 38.1 (95%confidence interval [CI]: 27.8-48.4), 35.7(95%CI: 23.4-48.0), and 29.7(95%CI: 22.8-36.6) months for Group A, Group B, and Group C, respectively (p=0.037). Multivariate analysis demonstrated that Group A and Group B had higher OS compared to Group C (hazard ratio [HR]=0.524, 95%CI: 0.307-0.894, p=0.018; HR=0.473, 95%CI: 0.241-0.931, p=0.030, respectively) among lung adenocarcinoma patients with EGFR mutations. With regard to patients with pleural or contralateral metastasis only, OS benefit (p=0.579) was not significant between the two groups. Subgroup analysis demonstrated that OS benefit in Group A was significant in patients with N0-1 disease and 21L858R mutations but not in EGFR exon 19 deletions, N2-3 stage or T3-4 stage patients. Conclusion: The prognosis of EGFR-mutant lung adenocarcinoma patients diagnosed only with intrathoracic metastasis was different, indicating that M1a staging should be refined.

Prognosis of EGFR-mutant advanced lung adenocarcinoma patients with different intrathoracic metastatic patterns.

Introduction: Lung cancer diagnosed solely with the presence of intrathoracic metastases is classified as M1a. However, intrathoracic metastases can be further divided into different patterns. The objective of our study was to analyze the differences in survival between the different metastatic patterns of intrathoracic metastases in lung adenocarcinoma patients who have epidermal growth factor receptor (EGFR) mutations.Materials and Methods: Patients who were diagnosed only with intrathoracic metastasis between March 2011 and October 2016 and had EGFR-mutations were selected for this study. Prognosis was determined based on metastatic patterns by univariate and multivariate analysis.Results: A total of 137 patients (60 patients who only had pleural metastasis [Group A], 44 patients who only had contralateral lung metastasis [Group B] and 33 patients who had both pleural and contralateral lung metastasis with or without pericardial effusion [Group C]) were selected for this in the study. The median OS (overall survival) time was 38.1 (95%confidence interval [CI]: 27.8-48.4), 35.7(95%CI: 23.4-48.0), and 29.7(95%CI: 22.8-36.6) months for Group A, Group B, and Group C, respectively (p=0.037). Multivariate analysis demonstrated that Group A and Group B had higher OS compared to Group C (hazard ratio [HR]=0.524, 95%CI: 0.307-0.894, p=0.018; HR=0.473, 95%CI: 0.241-0.931, p=0.030, respectively) among lung adenocarcinoma patients with EGFR mutations. With regard to patients with pleural or contralateral metastasis only, OS benefit (p=0.579) was not significant between the two groups. Subgroup analysis demonstrated that OS benefit in Group A was significant in patients with N0-1 disease and 21L858R mutations but not in EGFR exon 19 deletions, N2-3 stage or T3-4 stage patients.Conclusion: The prognosis of EGFR-mutant lung adenocarcinoma patients diagnosed only with intrathoracic metastasis was different, indicating that M1a staging should be refined.

P1.16-64 The Histological Predominant Pattern Could Predict Site of Recurrence and Metastasis in Surgically Treated Stage I Adenocarcinoma of the Lung

Pattern-based subtyping of adenocarcinoma of the lung is currently recommended due to prognostic implications. We aimed to evaluate whether predominant pattern subtype in surgically treated stage I adenocarcinoma of the lung can predict first site of recurrence or metastasis. We retrospectively reviewed clinical information, radiological findings, PET/CT-records, and pathological features (classified by IASLC/ATS/ERS subtyping criteria) of 906 Stage-I adenocarcinoma of the lung, who underwent surgery in 7 Centers. Patients were classified by histologic grade according to the IASLC/ATS/ERS classification as follow: intermediate grade (Invasive Lepidic, Acinar, Papillary) vs. high grade (Micropapillary, Solid) vs. NOS. The date of recurrence or metastases was defined as the first radiographic evidence of cancer relapse upon imaging or pathological tumour evidence from a biopsy. Univariate and multivariate logistic analysis were used to identify predictors of first site of recurrence or metastasis. A total of 248 (27%) patients developed recurrence or distant metastasis. The most commonly observed first location of recurrence was ipsilateral thorax (133 cases, 44%), followed by brain (27, 11%), contralateral lung (24, 10%), bones (11, 4%), liver and adrenal gland (10, 4%). Forty-three patients (17%) presented recurrence or metastasis in multiple sites simultaneously at the time of diagnosis. At multivariate analysis, patients with intermediate-grade histology developed intra-thoracic recurrence more frequently compared to the remainder of the cohort (odds ratio (OR) 1.85, 95% confidence interval (CI): 1.1– 3.18, P=0.038). Patients with high-grade histology developed contralateral lung metastasis (OR 2.1, 95%CI 1.1-4.2, P= 0.044) and brain metastasis (OR 2.5, 95%CI 1.3-5.1, P<0.01) more frequently compared to the low-grade ones. Predominant pattern subtype seems to predict site-specific recurrence and metastasis in surgically treated Stage I adenocarcinoma of the lung.

Clinical and radiological characteristics of central pulmonary adenocarcinoma: a comparison with central squamous cell carcinoma and small cell lung cancer and the impact on treatment response.

PurposeThe proportion of central pulmonary adenocarcinoma (ADC) in central-type lung cancer has been gradually increasing due to the overall increasing incidence of pulmonary ADC. But the clinical and radiological characteristics of central ADCs remain unclear. In this study, we compared the clinical and radiological characteristics of central ADCs with those of small cell lung cancers (SCLCs) and squamous cell carcinomas (SQCCs) and investigated the impact of these characteristics on patients’ treatment response.Patients and methodsThe medical records of 302 consecutive patients with central lung cancer from July 2014 to September 2016 were retrospectively reviewed. There were 99 patients with ADC, 95 with SQCC and 108 with SCLC. Computed tomography images were interpreted by two radiologists. Treatment response was determined by Response Evaluation Criteria In Solid Tumors 1.1.ResultsUnivariate analyses found that younger age, female sex, no history of smoking, higher levels of carcinoembryonic antigen (CEA), contralateral hilum lymphadenopathy, contralateral lung metastasis, pleural nodules and pleural metastasis to the interlobular fissure were significantly correlated with central ADC. Multivariate logistic regression analyses revealed that compared with central SQCC, female sex, younger age, no history of smoking, higher levels of CEA and contralateral hilum lymphadenopathy were the significantly independent indicators of central pulmonary ADC. Furthermore, compared with central SCLC, younger age, higher levels of CEA and cytokeratin 19 fragment (Cyfra21-1), lower levels of neuron-specific enolase, pleural nodules and lack of vascular involvement were significantly associated with central ADC. In 85 central ADC patients who received first-line platinum-based chemotherapy, both univariate and multivariate logistic regression analyses revealed that pulmonary emphysema had a negative correlation with treatment response (odds ratio=8.04, p=0.02).ConclusionOur study revealed that central pulmonary ADCs exhibited more aggressive clinical and radiological characteristics. Pulmonary emphysema was an independent and negative indicator for treatment response of central ADC.

Renal cell carcinoma with contralateral synchronous adrenal and lung metastasis: A rare case report

Renal cell carcinomas have propensity to metastasise to almost any organ. About 4.7–10.0% of these cases present with ipsilateral adrenal metastasis. The incidence of contralateral adrenal metastases are rare, they, however, can occur before, simultaneously or even after the primary neoplasm manifests clinically. Only a few synchronous and metachronous contra lateral adrenal metastases have been reported. We report a case of renal cell carcinoma with synchronous contralateral adrenal and lung metastasis.

P2.03b-004 Factors Associated with Brain Metastasis in Patients with Lung Adenocarcinoma after Surgical Resection: Topic: Brain Meta

The aim of the study is to demonstrate the relationship between clinicopathological variables and brain metastasis in patients with resected lung adenocarcinoma. The clinicopathological characteristics of 748 patients of resected lung adenocarcinoma at Taipei Veterans General Hospital between 2004 and 2012 were retrospectively reviewed. Comprehensive histological subtyping was performed according to the percentage of each invasive histologic component. The prognostic value of clinicopathological variables for brain metastasis-free survival was demonstrated. Among the 182 patients with distant metastasis, 93 (51.1%) patients developed contralateral lung metastasis, 81 (44.5%) had brain metastasis, 71 (39.0%) had bone metastasis, and 18 (8.9%) had liver metastasis during follow-up. Greater tumor size (Hazard ratio [HR], 1.276; 95% confidence interval [CI], 1.045 to 1.559; P = 0.017), stage II or III (vs. stage I) (HR, 2.469; 95% CI, 1.201 to 5.076; P = 0.014), angiolymphatic invasion (HR, 1.818; 95% CI, 1.037 to 3.189; P = 0.037), and micropapillary predominant (HR, 2.686; 95% CI, 1.270 to 5.683; P = 0.010) were significantly associated with more brain metastasis in multivariate analysis. Angiolymphatic invasion (HR, 2.632; 95% CI, 1.420 to 4.879; P = 0.002) and micropapillary predominant (HR, 2.186; 95% CI, 1.148 to 4.163; P = 0.017) were significant prognostic factors for worse brain metastasis-free survival in multivariate analysis. Angiolymphatic invasion and micropapillary predominant pattern are significantly associated with brain metastasis in patients with resected lung adenocarcinoma. This information is important for patient follow-up strategy and further study of the mechanisms leading to brain metastasis.

Factors predicting organ-specific distant metastasis in patients with completely resected lung adenocarcinoma.

The aim of the study is to demonstrate the relationship between clinicopathological variables and organ sites of metastasis in resected lung adenocarcinoma. The clinicopathological characteristics of 748 patients of resected lung adenocarcinoma at Taipei Veterans General Hospital between 2004 and 2012 were retrospectively reviewed. The prognostic value of clinicopathological variables for specific organ site metastasis-free survival was demonstrated. Among the 182 patients with distant metastasis, 93 (51.1%) patients developed contralateral lung metastasis, 81 (44.5%) had brain metastasis, 71 (39.0%) had bone metastasis, and 18 (8.9%) had liver metastasis during follow-up. Acinar predominant (Hazard ratio [HR], 0.468; 95% confidence interval [CI]: 0.250 to 0.877; P = 0.018) was significantly associated with less contralateral lung metastasis in multivariate analysis. Micropapillary predominant (HR, 2.686; 95% CI, 1.270 to 5.683; P = 0.010) was significantly associated with brain metastasis. Acinar predominant (HR, 0.461; 95% CI, 0.216 to 0.986; P = 0.046) was a significant prognostic factor for better contralateral lung metastasis-free survival in multivariate analysis. Micropapillary predominant (HR, 2.186; 95% CI, 1.148 to 4.163; P = 0.017) and solid predominant (HR, 4.093; 95% CI, 1.340 to 12.504; P = 0.013) were significant prognostic factors for worse brain metastasis-free survival and liver metastasis free-survival, respectively. There are significant differences in metastatic behavior between predominant pathological subtypes of lung adenocarcinoma. This information is important for patient follow-up strategy and identification of organ-specific distant metastasis. Prospective multi-institutional studies are mandatory for further validation.

Evaluation of Lung Cancer Patients with Distant Organ Metastasis

Objective :To evaluate the effects of distant organ metastasis on survival rates in patients with lung cancer Methods: Lung cancer patients with distant organ metastasis were enrolled to the study.Localization and histological types of primary tumors and metastasis, clinical symptoms and signs, the interaction of tumor and lymph nodes, the affects of metastasis on survival rates were evaluated. Results: Cytologic subgroups of patients were subdivided as non-small cell lung cancer (NSCLC) (75.3%) and small cell lung cancer (SCLC ) (24.7%). The most frequent metastatic sites were bone (41.4%), contralateral lung (32.8%),liver (23.9%),brain (27%), adrenal gland (19,5%). The most common metastasis sites for NSCLC and SCLC were bone and liver respectively. Metastatic pleural effusions mostly originated from adenocarcinoma and liver metastasis generally originated from small cell lung cancer. Having specific symptoms related to bone and brain were powerful predictors for metastasis. However specific symptoms of the liver was not well correlated with the existence of metastasis. Mean survival time was 198 days in all lung cancer patients with distant metastasis. The longest survival rate was in NSCLC patients with contralateral lung metastasis. Conclusion: Cytological types of the cancer, number of metastasis, weight loss, poor performance status, the absence of symptoms in SCLC with bone and brain metastasis, and presence of the symptoms in liver metastases had adverse affects on survival rates. Patients should be evaluated with combination of clinical symptoms, laboratory and radiological findings as whole so that it may prevent unnecessary surgery.

Sentinel lymph node biopsy in T1/T2 squamous cell carcinomas of the tongue: A prospective study.

Commonly used staging procedures often cannot predict the absence of cervical metastases (CM) in squamous cell carcinomas (SCCs) of the oral cavity. Due to the high incidence of occult CM in numerous N0 cases in the clinic, an elective neck dissection (ND) is performed. The sentinel lymph node biopsy (SNB) is a common concept in the modern surgical therapy of malignancies. The present study evaluates the applicability of this concept for T1/T2-SCC of the tongue. In a prospective clinical study, 10 consecutive patients with T1/T2-SCC of the tongue and cN0 necks, were enrolled. Following sentinel lymph node (SLN) scintigraphy, all patients underwent SNB with a γ-probe and a subsequent ND. SNB specimens were compared with histopathological assessments of surgical specimens from the ND. A total of 5 female and 5 male patients (mean age, 52 years; women, 62 years; men, 42 years), with a median follow-up time of 33.5 months (range, 10–40 months), were treated. All patients presented with detectable SLNs. In 7 cases, the SLN(s) and the residual ND were negative for CM. In 3 cases, the SLN(s) were positive without further CM in the other neck nodes. Furthermore, 1 patient showed additional CMs after 10 months in the contralateral neck and lung metastasis after 18 months, but none at the time of the initial treatment. The concept of an SNB appears to be applicable to the management of the cN0 neck in small SCC of the tongue. The role of SNB in the management of SCC requires further investigation by prospective trials with larger patient numbers.