1806PD Multiple primary cancers (MPC) in a series of lung cancer (LC) patient: Incidence and outcome
S. Cedres Perez1 , M. Sanso2 , A. Hernando-Calvo1 , A. Callejo1 , N. Pardo Aranda1 , A. Navarro Mendivil1 , A. Martinez1 , J. Remon1 , J.M. Miquel1 , G. Rodriguez1 , V. Monton1 , G. Villacampa3 , R. Dienstmann3 , A. Vivancos4 , E. Felip Font1 1
Medical Oncology, Vall d’Hebron University Hospital/Vall dHebron Institute Oncology, Barcelona, Spain,2
Cancer Genomics Group, Vall d’Hebron University Hospital/Vall dHebron Institute Oncology, Barcelona, Spain,3
Oncology Data Science, Vall d’Hebron University Hospital, Barcelona, Spain,4
Genomic Group, Vall d’Hebron University Hospital, Barcelona, Spain
Background: The number of cancer survivors has increased as a result of significant progress in prevention, diagnosis and treatment of malignant tumors and the incidence of MPC in surviving cancer patients (p) is also rising. This study investigates the co-occurrence of MPC among p diagnosed with lung cancer (LC).
Methods: Review of clinical data of all consecutive patients with histologically con-firmed LC visited at our institution between October 2017 and January 2018. Results: Out of 933 p, two primary cancers occurred in 115 cases (12%), including 25 p (3%) with three primary cancers. Patients with MPC were predominantly males (69%), smokers (85%) and 20% had known family history. Median age at the first tumor was 61 years (44-85). LC occurred as first neoplasm in 21% of the cases, as subsequent neo-plasm in 64% and as two consecutive primary neoneo-plasm in 15%. Most common cancer previous to LC diagnosis was colorectal in 23%, breast in 22%, prostate in 19%, head and neck in 12% and bladder in 11%. Treatment received for first cancer included sur-gery in 79%, chemotherapy in 50% and radiotherapy in 30%. Second tumor was pros-tate in 22%, bladder in 22%, colorectal in 19%, breast in 19% and head and neck in 8%. Surgery was performed in 66% of the cases with second cancer. Overall, median time from diagnosis of first to second neoplasm was 4 years (2.9 -5.2), without significant differences if primary tumor was LC or another neoplasm (p¼ 0.39). Of note, 25% had diagnosis of second primary cancer within 1 year. Smoking was significantly associated with shorter time to diagnosis of a second neoplasm (3.4 years vs 4.7 years for non-smokers, p¼ 0.03). With a median follow up of 2 years after diagnosis of second neo-plasm, the 2-year survival rate was 93.7% (88.8-98.7%). Having a second cancer within 3 years significantly increased the risk of death (HR¼ 7.7, p ¼ 0.02).
Conclusions: In our series, the frequency of the co-occurrence of MPC among LC p is 12%, indicating that surveillance strategies are recommended. Many p are treated with curative intent. Smoking increased risk of second primary, and diagnosis within 3 years of follow-up associates with poor outcome.
Legal entity responsible for the study: Vall d’Hebron Institute Oncology. Funding: Has not received any funding.
Disclosure: All authors have declared no conflicts of interest.
1807P STELLAR: Final results of a phase II trial of TTFields with chemotherapy for first-line treatment of pleural mesothelioma
F. Grosso1 , J.G. Aerts2 , J. Madrzak3 , R. Dziadziuszko3 , R. Ramlau4 , S. Cedres5 , B. Hiddinga6 , J.P. van Meerbeeck6 , M. Mencoboni7 , D. Planchard8 , A. Chella9 , L. Crino10 , M.J. Krzakowski11 , G.L. Ceresoli12 1
Oncology, SS Antonio e Biagio Hospital, Department of Oncology, Alessandria, Italy, 2
Oncology, Erasmus University Medical Center, Rotterdam, Netherlands,3 Oncology, Medical University of Gdansk Clinical Hospital, Gdansk, Poland,4
Oncology, Medical University of Poznan, Poznan, Poland,5
Oncology, Vall d’Hebron University Hospital, Barcelona, Spain,6
Oncology, Antwerp University Hospital, Antwerp, Belgium, 7
Oncology, Ospedale Villa Scassi, Genoa, Italy,8
Oncology, Institut Gustave Roussy, Villejuif, France,9
Oncology, Cisanello University Hospital Pisa, Pisa, Italy,10 Oncology, Ospedale S. Maria della Misericordia, Perugia, Italy,11
Department of Lung & Thoracic Tumours, The Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland,12
Oncology, Humanitas Gavazzeni, Bergamo, Italy
Background:Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, using low intensity alternating electric fields delivered non-invasively to the tumor using a portable, medical device. In vitro, human mesothelioma cells were highly susceptible to TTFields. TTFields have been shown to extend survival of patients with glioblastoma when added to chemotherapy.
Methods:The trial accrued 80 patients with unresectable, untreated mesothelioma. Patients were treated with continuous 150 kHz TTFields in combination with peme-trexed and platinum. Inclusion criteria included ECOG 0-1 and at least one measurable lesion according to modified RECIST. Patients were followed q3w (CT scan q6w) until
disease progression. The primary endpoint was overall survival (OS). This single arm study assumed historical control with a median survival of 12.1 months (Vogelzang et al. 2003). The sample size provided 80% power with a two-sided alpha of 0.05 to detect an increase in median OS of 5.5 months.
Results:All patients had a minimum follow up of 12 months. Median age was 67 (range 27-78), 84% were male and 56% smokers. 16% (13 patients) had metastatic disease and 44% (35 patients) had an ECOG PS of 1. 66% (53 patients) had epithelioid histology. Compliance with TTFields was 68% (16.3 hours/day) during the first 3 months of ther-apy. Median OS was 18.2 months (95% CI 12.1-25.8) compared to 12.1 months in his-torical controls. Median PFS was 7.6 months (95% CI 6.7-8.6) compared to 5.7 months in historical controls. Partial responses were seen in 40.3% of patients and clinical bene-fit (PRþSD) was seen in 97.2% of patients. No device-related serious adverse events (AEs) were reported. Expected TTFields-related dermatitis was reported in 46% (37 patients). Only 4 patients (5%) had grade 3 dermatitis.
Conclusions:The study met its primary endpoint of significant extension of survival for previously untreated mesothelioma patients. Secondary efficacy endpoints were also improved compared to historical control. The study demonstrated no safety con-cerns for the combination of TTFields to the thorax with chemotherapy. These results support the addition of TTFields to chemotherapy in the first-line treatment of malig-nant pleural mesothelioma.
Clinical trial identification:NCT02397928.
Legal entity responsible for the study:Novocure.
Funding:Novocure.
Disclosure:J.G. Aerts: Advisory boards: BMS, MSD, Roche, AstraZeneca, Eli Lilly, Boehringer Ingelheim, Amphera; Stock owner: Amphera. R. Ramlau: Consultant: Novocure. All other authors have declared no conflicts of interest.
1808P Role of evaluating tumor infiltrating lymphocytes, programmed death-ligand 1 and mismatch-repair proteins expression in malignant mesothelioma L. Losi1 , F. Bertolini2 , L. Scurani1 , G. Guaitoli2 , C. Baldessari2 , A. Ambrosini Spaltro3 , L. Botticelli3 , A. Maiorana3 , F. Barbieri2 , S. Cascinu2 1
Department of Life Sciences, Unit of Pathology, University of Modena and Reggio Emilia, Modena, Italy,2
Department of Oncology and Haematology, Azienda Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy,3
Department of Diagnostic Medicine, Clinic and Public Health, Unit of Pathology, University of Modena and Reggio Emilia, Modena, Italy
Background: Malignant mesothelioma (MM) is an aggressive and fatal tumor, mainly related to prolonged exposure to asbestos. MM can induce infiltration of immune cells and immunity-mediated death. Tumor microenvironment plays a major role in neo-plastic progression, favoring tumor cell evasion from adaptive immunity and T-cell checkpoint pathways. Expression of programmed death-ligand 1 (PD-L1) on tumor cells and tumor-infiltrating lymphocytes (TILs) has been described in literature. Cancer cells expressing PD-L1 increase apoptosis of antigen-specific human T-cell clones and inhibit CD4þ and CD8þ T-cell activation, thus decreasing the immune action on the tumor cells. Some mismatch repair–deficient tumors make them sensitive to immune checkpoint blockade, because of the increased number of neoantigens encoded by cancers, which enhances anti-tumor response.
Methods: The aim of this study is to analyze the expression of PD-L1 on both tumor cells and TILs and to characterize TILs. Furthermore, MisMatchRepair (MMR) protein expression was evaluated. Immunohistochemistry was applied using the automated system BenchMark XT (VENTANA) for PD-L1 (DAKO, clone 22C3), CD4, CD8 and MLH1, MSH2, MSH6, PMS2.
Results: 55 malignant mesotheliomas, 10 from women and 45 from men, were studied. The range of age was 43-88 years old. Tumors consisted of 44 epithelioid, 3 sarcomatoid, 7 biphasic and 1 desmoplastic. 51 were localized to pleura and 4 to peri-toneum. 18 tumors were in stage I, 13 in stage II, 15 in stage III and 5 in stage IV. For 4 cases the stage was not evaluable. Our results showed expression of PD-L150% in tumor cells in 9 cases (5 epithelioid, 2 sarcomatoid, 1 biphasic and 1 desmoplastic). In two of these the positivity was observed both in tumor cells and in TILs. 15 tumors were negative and 31 showed a positive staining1. A presence of TILs was observed in 53 cases. A prevalence of CD4þ expression was highlighted in 45 cases. 6 of them showed elevated expression of PD-L1 (50%). Alteration in MMR staining was not found.
Conclusions: Our data underline the role of tumor immune microenvironment and its characterization in MM and open the possibility to use combined therapies according to different PD-L1 expression.
VCEuropean Society for Medical Oncology 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
Annals of Oncology 29 (Supplement 8): viii641–viii644, 2018 doi:10.1093/annonc/mdy301
