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European journal of cancer 22건

  1. [해외논문]   Integrative expression quantitative trait locus–based analysis of colorectal cancer identified a functional polymorphism regulating SLC22A5 expression   SCI SCIE SCOPUS

    Zou, Danyi (<i>Corresponding author</i>: Fax: +86 27 8369 3673. ) , Lou, Jiao (<i>Corresponding author</i>: Fax: +86 27 8369 3673.) , Ke, Juntao , Mei, Shufang , Li, Jiaoyuan , Gong, Yajie , Yang, Yang , Zhu, Ying , Tian, Jianbo , Chang, Jiang , Zhong, Rong , Gong, Jing , Miao, Xiaoping
    European journal of cancer v.93 ,pp. 1 - 9 , 2018 , 0959-8049 ,

    초록

    Abstract Multiple single nucleotide polymorphisms (SNPs) have been found to be highly correlated with colorectal cancer (CRC) risk. However, the variants identified thus far only explain a small part of the cases, suggesting the existence of many uncharacterised genetic determinants. In this study, using the multilevel ‘omics’ data provided in The Cancer Genome Atlas, we systematically performed expression quantitative trait locus (eQTL) analysis for CRC and identified nine SNPs with significant effects on mRNA expression (correlation |r| > 0.3 and FDR SLC22A5 was significantly correlated with CRC risk in both stages and the combined study (additive model, OR = 1.31, 95%CI = 1.17–1.47, P = 1.97 × 10 −6 ). eQTL analysis showed that rs27437 GG and GA genotypes were associated with lower expression of SLC22A5 compared with the AA genotype. Dual-luciferase reporter assays confirmed that the G risk allele could decrease the expression of luciferase. SLC22A5 was significantly decreased in CRC tumour tissues compared with adjacent normal tissues, indicating that SLC22A5 may play important roles in CRC, and rs27437 in SLC22A5 might serve as a novel biomarker for early detection and prevention of CRC. Highlights eQTL analysis was performed using the data from TCGA. The potentially functional single nucleotide polymorphisms (SNPs) were validated in the Chinese population. rs27437 in gene SLC22A5 was demonstrated to be associated with CRC risk. The effect of the SNP was confirmed by luciferase reporter assays.

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  2. [해외논문]   Hallmarks of cancer: The CRISPR generation   SCI SCIE SCOPUS

    Moses, Colette (Cancer Epigenetics Laboratory, Harry Perkins Institute of Medical Research, Perth, Australia ) , Garcia-Bloj, Benjamin (Cancer Epigenetics Laboratory, Harry Perkins Institute of Medical Research, Perth, Australia ) , Harvey, Alan R. (School of Human Sciences, The University of Western Australia, Perth, Australia ) , Blancafort, Pilar (Cancer Epigenetics Laboratory, Harry Perkins Institute of Medical Research, Perth, Australia)
    European journal of cancer v.93 ,pp. 10 - 18 , 2018 , 0959-8049 ,

    초록

    Abstract The hallmarks of cancer were proposed as a logical framework to guide research efforts that aim to understand the molecular mechanisms and derive treatments for this highly complex disease. Recent technological advances, including comprehensive sequencing of different cancer subtypes, have illuminated how genetic and epigenetic alterations are associated with specific hallmarks of cancer. However, as these associations are purely descriptive, one particularly exciting development is the emergence of genome editing technologies, which enable rapid generation of precise genetic and epigenetic modifications to assess the consequences of these perturbations on the cancer phenotype. The most recently developed of these tools, the system of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), consists of an RNA-guided endonuclease that can be repurposed to edit both genome and epigenome with high specificity, and facilitates the functional interrogation of multiple loci in parallel. This system has the potential to dramatically accelerate progress in cancer research, whether by modelling the genesis and progression of cancer in vitro and in vivo , screening for novel therapeutic targets, conducting functional genomics/epigenomics, or generating targeted cancer therapies. Here, we discuss CRISPR research on each of the ten hallmarks of cancer, outline potential barriers for its clinical implementation and speculate on the advances it may allow in cancer research in the near future. Highlights CRISPR-Cas systems allow efficient, directed editing of the genome and epigenome. CRISPR has advanced our understanding of the mechanisms underlying cancer hallmarks. CRISPR editing rapidly generates complex cancer model systems in vitro and in vivo . High-throughput CRISPR screens identify novel drug targets and oncogenic drivers. CRISPR has the potential to provide new forms of personalised cancer medicine.

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  3. [해외논문]   A phase III study comparing SB3 (a proposed trastuzumab biosimilar) and trastuzumab reference product in HER2-positive early breast cancer treated with neoadjuvant-adjuvant treatment: Final safety, immunogenicity and survival results   SCI SCIE SCOPUS

    Pivot, X. (Administrateur de l'Institut Régional du Cancer, 3 rue de la porte de l'hôpital, BP 30042, 67065, Strasbourg Cedex, France ) , Bondarenko, I. (Oncology and Medical Radiology Department, Dnipropetrovsk Medical Academy, Dnipropetrovsk, Ukraine ) , Nowecki, Z. (Department of Oncology, M Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland ) , Dvorkin, M. (Department of Oncology, Clinical Oncology Dispensary, Omsk, Russia ) , Trishkina, E. (Department of Oncology, Leningrad Regional Oncology Centre, St. Petersburg, Russia ) , Ahn, J.-H. (Department of Oncology, Asan Medical Center, Seoul, Republic of Korea ) , Im, S.-A. (Department of Oncology, Seoul National University Hospital, Seoul, Republic of Korea ) , Sarosiek, T. (Department of Clinical Oncology, Centrum Medyczne Ostrobramska NZOZ MAGODENT, Warsaw, Poland ) , Chatterjee, S. (Department of Oncology, Tata Medical Centre, Kolkata, India ) , Wojtukiewicz, M.Z. (Department of Oncology, Medical University of Bialystok, Bialystok, Poland ) , Shparyk, Y. (Chemotherapy Department, Lviv State Oncological Regional Treatment and Diagnostic Center, Lviv, Ukra) , Moiseyenko, V. , Bello III, M. , Semiglazov III, V. , Lee III, Y. , Lim III, J.
    European journal of cancer v.93 ,pp. 19 - 27 , 2018 , 0959-8049 ,

    초록

    Abstract Background The equivalent efficacy between SB3, a proposed trastuzumab biosimilar, and the trastuzumab reference product (TRZ) in terms of the breast pathologic complete response rate after neoadjuvant therapy in patients with early or locally advanced human epidermal growth factor receptor 2-positive breast cancer was demonstrated in the previous report. Here, we report the final safety, immunogenicity and survival results after neoadjuvant-adjuvant treatment. Patients and methods Patients were randomised 1:1 to receive neoadjuvant SB3 or TRZ for 8 cycles concurrently with chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide). Patients then underwent surgery, followed by 10 cycles of adjuvant SB3 or TRZ as randomised. End-points included safety, immunogenicity, event-free survival (EFS) and overall survival through the adjuvant period. Results Of 875 patients randomised, 764 (SB3, n = 380; TRZ, n = 384) completed the study. The median follow-up duration was 437 days in the SB3 group and 438 days in the TRZ group. The incidence of treatment-emergent adverse events was comparable between groups (SB3, 97.5%; TRZ, 96.1%) during the overall study period. Up to the end of study, the overall incidence of antidrug antibody was low in both treatment groups (3 patients each). EFS was comparable between groups with a hazard ratio (SB3/TRZ) of 0.94 (95% confidence interval, 0.59–1.51) and EFS rates at 12 months of 93.7% for SB3 and 93.4% for TRZ. Conclusions Final safety, immunogenicity and survival results of this study further support the biosimilarity established between SB3 and TRZ. Trial registration ClinicalTrials.gov (NCT02149524); EudraCT ( 2013-004172-35 ). Highlights Equivalent efficacy between SB3 and Herceptin ? in terms of the breast pathologic complete response rate was established. Event-free survival and overall survival results further support the biosimilarity established between SB3 and Herceptin ? . Safety and immunogenicity results were highly comparable with no clinically relevant differences between SB3 and Herceptin ? .

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  4. [해외논문]   High-risk soft tissue sarcomas treated with perioperative chemotherapy: Improving prognostic classification in a randomised clinical trial   SCI SCIE SCOPUS

    Pasquali, Sandro (Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy ) , Colombo, Chiara (Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy ) , Pizzamiglio, Sara (Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy ) , Verderio, Paolo (Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy ) , Callegaro, Dario (Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy ) , Stacchiotti, Silvia (Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy ) , Martin Broto, Javier (Department of Cancer Medicine, Hospital Universitario Virgen del Rocio, Sevilla, Spain ) , Lopez-Pousa, Antonio (Department of Cancer Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain ) , Ferrari, Stefano (Department of Cancer Medicine, Istituto Ortopedico Rizzoli, Bologna, Italy ) , Poveda, Andres (Department of Cancer Medicine, Valencian Oncologic Institute, Valencia, Spain ) , De Paoli, Antonino (Department of Radiation Oncology, Centro di Riferimento Oncologico, Aviano) , Quagliuolo, Vittorio , Jurado, Josefina Cruz , Comandone, Alessandro , Grignani, Giovanni , De Sanctis, Rita , Palassini, Elena , Llomboart-Bosch, Antonio , Dei Tos, Angelo Paolo , Casali, Paolo G. , Picci, Piero , Gronchi, Alessandro
    European journal of cancer v.93 ,pp. 28 - 36 , 2018 , 0959-8049 ,

    초록

    Abstract Background Patients with extremity and trunk wall soft tissue sarcoma (STS) with high malignancy grade and size >5 cm are at high-risk of death. This risk varies depending also on other patient and tumour features, including histologic subtype. This study investigated whether a prognostic nomogram can improve risk assessment of these patients. Methods Data from high-risk STS patients enrolled in a randomised controlled trial investigating different perioperative chemotherapy regimens were analysed. Ten-year probability of overall survival (OS) and incidence of distant metastasis (DM) were computed using the prognostic nomogram Sarculator (pr-OS and inc-DM, respectively). Tumour response according to RECIST and Choi criteria was also investigated. Findings Variation in pr-OS and inc-DM were observed and patients stratified in three prognostic groups. The 10-year OS in the low, intermediate, and high pr-OS categories were 0·42 (95%CI 0·32–0·52), 0·63 (95%CI 0·53–0·72), and 0·78 (95%CI 0·68–0·85), respectively. Patients in the intermediate (HR 0·51, P = 0·002) and high (HR 0·28, P Interpretation Sarculator identifies variations in outcomes of high-risk STS treated with perioperative chemotherapy and improve prognostic classification, which is also associated with different patterns of tumour response, an outcome that further stratifies survival particularly for patients predicted at higher risk. Future trials investigating neoadjuvant chemotherapy should consider prognostic tool for selecting patients to be enrolled. Trial registration number European Union Drug Regulating Authorities Clinical Trials No. 2004-003979-36. Highlights Wide variations exist in prognosis of patients with currently defined high-risk STS. The prognostic tool Sarculator stratified three prognostic groups of high-risk STS. Tumour response according to Choi after neoadjuvant chemotherapy stratifies prognosis.

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  5. [해외논문]   Diversity of brain metastases screening and management in non-small cell lung cancer in Europe: Results of the European Organisation for Research and Treatment of Cancer Lung Cancer Group survey   SCI SCIE SCOPUS

    Levy, Antonin (Department of Radiation Oncology, Gustave Roussy, Institut d'Oncologie Thoracique (IOT), INSERM U1030 Molecular Radiotherapy, Université) , Faivre-Finn, Corinne (Paris-Saclay, F-94805, Villejuif, France ) , Hasan, Baktiar (Manchester Academic Health Science Centre, Institute of Cancer Sciences, Manchester Cancer Research Centre (MCRC), University of Manchester, Manchester, UK ) , De Maio, Eleonora (European Organisation for Research and Treatment of Cancer, Brussels, Belgium ) , Berghoff, Anna S. (European Organisation for Research and Treatment of Cancer, Brussels, Belgium ) , Girard, Nicolas (Department of Medicine I and Comprehensive Cancer Center CNS Unit (CCC-CNS), Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria ) , Greillier, Laurent (Department of Medical Oncology, Institut Curie, Paris, France ) , Lantué (Multidisciplinary Oncology and Therapeutic Innovations, Assistance Publique Hôpitaux de Marseille, Aix Marseille University, Marseille, France ) , joul, Sylvie (Department of Biopathology, Centre Léon Bérard UNICANCER, Lyon, Université) , O'Brien, Mary (Grenoble Alpes, INSERM U120) , Reck, Martin , Dingemans, Anne-Marie C. , Novello, Silvia , Berghmans, Thierry , Besse, Benjamin , Hendriks, Lizza
    European journal of cancer v.93 ,pp. 37 - 46 , 2018 , 0959-8049 ,

    초록

    Abstract Background Brain metastases (BM) are frequent in non-small cell lung cancer (NSCLC) patients, but there is a lack of evidence-based management of this patient group. We aimed to capture a snapshot of routine BM management in Europe to identify relevant research questions for future clinical trials. Methods An EORTC Lung Cancer Group (LCG) online survey containing questions on NSCLC BM screening and treatment was distributed between 16/02/17 and 15/06/17 to worldwide EORTC LCG members, and through several European scientific societies in the thoracic oncology field. Results A total of 462 European physician responses (394 institutions) were analysed (radiation oncologist: 53% [n = 247], pulmonologist: 26% [n = 119], medical oncologist: 18% [n = 84]; 84% with >5 years' experience in NSCLC). Italy (18%, n = 85), Netherlands (15%, n = 68), UK (14%, n = 66), and France (12%, n = 55) contributed most. 393 physicians (85%) screened neurologically asymptomatic patients for BM at diagnosis (52% using magnetic resonance imaging). Most often screened patients were those with a driver mutation (MUT+; 51%, n = 234), stage III (63%, n = 289), and IV (43%, n = 199). 158 physicians (34%) used a prognostic classification to guide initial treatment decisions, and in 50%, lowest prognostic-score threshold to receive treatment differed between MUT+ and non-driver mutation (MUT−) patients. MUT+ patients with >4 BM were more likely to receive stereotactic radiosurgery (SRS) compared with MUT− (27% versus. 21%; p 5 BM was systemic treatment (79%). Of all, 45%/49% physicians stated that all tyrosine kinase inhibitors and immune checkpoint blockers were discontinued (timing varied) during SRS/WBRT, respectively. Drugs most often continued during SRS/WBRT were erlotinib (44%/40%), gefitinib (39%/34%), afatinib (29%/25%), crizotinib (33%/26%) and anti-PD-(L)-1 (28%/22%). Conclusion BM management is highly variable in Europe: screening is not uniform, prognostic classifications are not often used and MUT+ NSCLC patients generally receive more intensive local treatment. Prospective assessment of BM management in MUT+ NSCLC patients is required. Highlights This EORTC survey found that European BM management is not according to European guidelines. BM screening is not uniform, prognostic classifications are not often used, and MUT + NSCLC patients receive more intensive local treatment. Efforts in harmonisation of management of BM should be pursued by cancer societies. For MUT + NSCLC patients, specific BM guidelines and trials are required.

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  6. [해외논문]   Blood classification and blood response criteria in mycosis fungoides and SEzary syndrome using flow cytometry: recommendations from the EORTC cutaneous lymphoma task force   SCI SCIE SCOPUS

    Scarisbrick, Julia J. (University Hospital Birmingham, UK ) , Hodak, Emmilia (Rabin Medical, Beilinson Hospital, Tel Aviv University, Israel ) , Bagot, Martine (Hospital St Louis, Paris, France ) , Stranzenbach, Rene (JW Medical Centre, University Hospital of Ruhr-University Bochum, Germany, Minden, Germany ) , Stadler, Rudolf (JW Medical Centre, University Hospital of Ruhr-University Bochum, Germany, Minden, Germany ) , Ortiz-Romero, Pablo L. (Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid, Spain ) , Papadavid, Evangelia (National and Kapodistrian University of Athens, Medical School, Greece ) , Evison, Felicity (University Hospital Birmingham, UK ) , Knobler, Robert (Medical University of Vienna, Austria ) , Quaglino, Pietro (University of Turin (Torino), Italy ) , Vermeer, Maarten H. (Leiden University Medical Centre, The Netherlands)
    European journal of cancer v.93 ,pp. 47 - 56 , 2018 , 0959-8049 ,

    초록

    Abstract Our current mycosis fungoides (MF) and SEzary Syndrome (SS) staging system includes blood-classification from B0-B2 for patch/plaque/tumour or erythroderma based on manual SEzary counts but results from our EORTC survey confirm these are rarely performed in patch/plaque/tumour MF, and there is a trend towards using flow cytometry to measure blood-class. Accurately assigning blood-class effects overall stage and the ‘global response’ used to measure treatment responses in MF/SS and hence impacts management. The EORTC Cutaneous Lymphoma Task Force Committee have reviewed the literature and held a Workshop (June 2017) to agree a definition of blood-class according to flow cytometry. No large study comparing blood-class as defined by SEzary count with flow cytometry has been performed in MF/SS. The definition of blood-class by flow cytometry varies between publications. Low-level blood involvement occurs in patch/plaque/tumour much less than erythroderma (p For consistency flow, definition for blood-class must be an objective measurement. We propose absolute counts of either CD4+CD7-or CD4+CD26-where B0 Highlights Blood-class was introduced into staging of MF/SS in 2007 using manual Sezary counts which are rarely performed in all stages. Flow cytometry has largely replaced manual Sezary counts for monitoring blood involvement in MF/SS. Flow cytometry should define blood class according to absolute counts of CD4+7- or CD4+26- populations. Clinical significance of variation in blood-class between B0/B1 has not been proven and should not be considered in response criteria.

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  7. [해외논문]   Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma   SCI SCIE SCOPUS

    El-Galaly, Tarec Christoffer (Department of Hematology, Aalborg University Hospital, Aalborg, Denmark ) , Cheah, Chan Yoon (Department of Haematology, Sir Charles Gairdner Hospital, Perth, Australia ) , Bendtsen, Mette Dahl (Department of Hematology, Aalborg University Hospital, Aalborg, Denmark ) , Nowakowski, Grzegorz S. (Division of Hematology, Mayo Clinic, Rochester, USA ) , Kansara, Roopesh (Section of Medical Oncology and Hematology, Cancer Care Manitoba, Department of Internal Medicine, University of Manitoba, Winnipeg, Canada ) , Savage, Kerry J. (Division of Medical Oncology and Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada ) , Connors, Joseph M. (Division of Medical Oncology and Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada ) , Sehn, Laurie H. (Division of Medical Oncology and Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada ) , Goldschmidt, Neta (Hematology Department, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel ) , Shaulov, Adir (Hematology Department, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel ) , Farooq, Umar (Division of Hematology, Oncology, Blood & Marrow Transpl) , Link, Brian K. , Ferreri, André , s J.M. , Calimeri, Teresa , Cecchetti, Caterina , Dann, Eldad J. , Thompson, Carrie A. , Inbar, Tsofia , Maurer, Matthew J. , Gade, Inger Lise , Juul, Maja Bech , Hansen, Jakob W. , Holmberg, Staffan , Larsen, Thomas S. , Cordua, Sabrina , Mikhaeel, N. George , Hutchings, Martin , Seymour, John F. , Clausen, Michael Roost , Smith, Daniel , Opat, Stephen , Gilbertson, Michael , Thanarajasingam, Gita , Villa, Diego
    European journal of cancer v.93 ,pp. 57 - 68 , 2018 , 0959-8049 ,

    초록

    Abstract Purpose Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) Methods Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records. Results In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15–25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ≤60 years, performance status 0–1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0–1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36–80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9). Conclusions In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions. Highlights The overall prognosis of secondary CNS relapse of diffuse large B-cell lymphoma remains poor. Few patients achieve favourable long-term outcomes with current therapies. Younger patients with parenchymal SCNS and no systemic involvement have a relatively good prognosis after intensive therapies. The addition of rituximab to HDMTX-based regimens seems to improve outcomes.

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  8. [해외논문]   Clonal evolution and heterogeneity in metastatic head and neck cancer—An analysis of the Austrian Study Group of Medical Tumour Therapy study group   SCI SCIE SCOPUS

    Melchardt, Thomas (IIIrd Medical Department with Hematology and Medical Oncology, Paracelsus Medical University Salzburg, Salzburg, Austria ) , Magnes, Teresa (IIIrd Medical Department with Hematology and Medical Oncology, Paracelsus Medical University Salzburg, Salzburg, Austria ) , Hufnagl, Clemens (IIIrd Medical Department with Hematology and Medical Oncology, Paracelsus Medical University Salzburg, Salzburg, Austria ) , Thorner, Aaron R. (Center for Cancer Genome Discovery, Dana Farber Cancer Center, Boston, USA ) , Ducar, Matthew (Center for Cancer Genome Discovery, Dana Farber Cancer Center, Boston, USA ) , Neureiter, Daniel (Department of Pathology, Paracelsus Medical University, Salzburg, Austria ) , Trä (Department of Pathology, Paracelsus Medical University, Salzburg, Austria ) , nkenschuh, Wolfgang (Department of Pathology, Paracelsus Medical University, Salzburg, Austria ) , Klieser, Eckhard (Department of Oral and Maxillofacial Surgery, Paracelsus Medical University, Salzburg, Austria ) , Gaggl, Alexander (Department of Otorhinolaryngology, Paracelsus Medical University, Salzburg, Austria ) , Rö (Department of Otorhinolaryngology, Paracelsus Medical University,) , sch, Sebastian , Rasp, Gerd , Hartmann, Tanja N. , Pleyer, Lisa , Rinnerthaler, Gabriel , Weiss, Lukas , Greil, Richard , Egle, Alexander
    European journal of cancer v.93 ,pp. 69 - 78 , 2018 , 0959-8049 ,

    초록

    Abstract Background Tumour heterogeneity and clonal evolution within a cancer patient are deemed responsible for relapse in malignancies and present challenges to the principles of targeted therapy, for which treatment modality is often decided based on the molecular pathology of the primary tumour. Nevertheless, the clonal architecture in distant relapse of head and neck cancer is fairly unknown. Patients and methods For this project, we analysed a cohort of 386 patients within the Austrian Registry of head and neck cancer. We identified 26 patients with material from the primary tumour, the distant metastasis after curative first-line treatment and a germline sample for analysis of clonal evolution. After pathological analyses, these samples were analysed using a targeted massively parallel sequencing (MPS) panel of 257 genes known to be recurrently mutated in head and neck cancer plus a genome-wide SNP-set. Results Despite histological diagnosis of distant metastasis, no corresponding mutation in the supposed metastases was found in two of 23 (8.6%) evaluable patients suggesting a primary tumour of the lung instead of a distant metastasis of head and neck cancer. We observed a branched pattern of evolution in 31.6% of the analysed patients. This pattern was associated with a shorter time to distant metastasis, compared with a pattern of punctuated evolution. Structural genomic changes over time were also present in 7 of 12 (60%) evaluable patients with metachronous metastases. Conclusion Targeted MPS demonstrated substantial heterogeneity at the time of diagnosis and a complex pattern of evolution during disease progression in head and neck cancer. Copy number analyses revealed additional changes that were not detected by mutational analyses. Mutational and structural changes contribute to tumour heterogeneity at diagnosis and progression. Highlights A branched pattern of evolution was present in 32% of patients with distant metastasis of head and neck cancer. This pattern was associated with a shorter time to distant metastasis. No corresponding mutation in the supposed metastases was found in 8.6% of the patients suggesting another tumour of instead of a distant metastasis.

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  9. [해외논문]   Health-related quality of life of adjuvant chemotherapy with S-1 versus gemcitabine for resected pancreatic cancer: Results from a randomised phase III trial (JASPAC 01)   SCI SCIE SCOPUS

    Hagiwara, Yasuhiro (Department of Biostatistics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan ) , Ohashi, Yasuo (Department of Integrated Science and Engineering for Sustainable Society, Chuo University, 1-13-27 Kasuga, Bunkyo, Tokyo 112-8551, Japan ) , Uesaka, Katsuhiko (Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007 Shimo-Nagakubo, Nagaizumi, Sunto, Shizuoka 411-8777, Japan ) , Boku, Narikazu (Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo, Tokyo 104-0045, Japan ) , Fukutomi, Akira (Division of Gastrointestinal Oncology, Shizuoka Cancer Center Hospital, 1007 Shimo-Nagakubo, Nagaizumi, Sunto, Shizuoka 411-8777, Japan ) , Okamura, Yukiyasu (Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007 Shimo-Nagakubo, Nagaizumi, Sunto, Shizuoka 411-8777, Japan ) , Konishi, Masaru (Department of Hepatobiliary-Pancreatic Surgery, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan ) , Matsumoto, Ippei (Division of Hepato-Biliary-Pancreatic Sur) , Kaneoka, Yuji , Shimizu, Yasuhiro , Nakamori, Shoji , Sakamoto, Hirohiko , Morinaga, Soichiro , Kainuma, Osamu , Imai, Koji , Sata, Naohiro , Hishinuma, Shoichi , Ojima, Hitoshi , Yamaguchi, Ryuzo , Hirano, Satoshi , Sudo, Takeshi
    European journal of cancer v.93 ,pp. 79 - 88 , 2018 , 0959-8049 ,

    초록

    Abstract Background Adjuvant chemotherapy with S-1 for resected pancreatic cancer demonstrated survival benefits compared with gemcitabine in the JASPAC 01 trial. We investigated the effect of these agents on health-related quality of life (HRQOL) of patients in the JASPAC 01 trial. Methods Patients with resected pancreatic cancer were randomly assigned to receive gemcitabine (1000 mg/m 2 weekly for three of four weeks for up to six cycles) or S-1 (40, 50, or 60 mg twice daily for four of six weeks for up to four cycles). HRQOL was assessed using the EuroQol-5D-3L (EQ-5D) questionnaire at baseline, months three and six, and every 6 months thereafter. HRQOL end-points included change in EQ-5D index from baseline, responses to five items in the EQ-5D, and quality-adjusted life months up to 24 months. Results Of randomised 385 patients, 354 patients were included in HRQOL analysis. Mean change in the EQ-5D index was similar in the S-1 and gemcitabine groups within 6 months from treatment initiation (difference, 0.024; P = 0.112), whereas corresponding mean from 12 to 24 months was better in the S-1 group than in the gemcitabine group (difference, 0.071; P P Conclusion Adjuvant chemotherapy with S-1 does not improve HRQOL within 6 months from treatment initiation but does improve HRQOL thereafter and quality-adjusted life months. Clinical trial registration number UMIN000000655 at UMIN CTR. Highlights Health-related quality of life (HRQOL) in the JASPAC 01 trial was analysed. The trial compared adjuvant S-1 with gemcitabine for resected pancreatic cancer. HRQOL within 6 months was similar between the two treatments. HRQOL from 12 to 24 months was better with S-1 than with gemcitabine. Quality-adjusted life months were longer with S-1 than with gemcitabine.

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  10. [해외논문]   The use of intensive radiological assessments in routine surveillance after treatment for head and neck cancer: An economic evaluation   SCI SCIE SCOPUS

    Meregaglia, Michela (Department of Health Services Research and Policy, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, WC1H9SH, London, UK ) , Cairns, John (Department of Health Services Research and Policy, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, WC1H9SH, London, UK ) , Licitra, Lisa (Head and Neck Medical Oncology Department, IRCCS Foundation National Cancer Institute, University of Milan, Via Venezian 1, 20133, Milan, Italy ) , Bossi, Paolo (Head and Neck Medical Oncology Department, IRCCS Foundation National Cancer Institute, University of Milan, Via Venezian 1, 20133, Milan, Italy)
    European journal of cancer v.93 ,pp. 89 - 98 , 2018 , 0959-8049 ,

    초록

    Abstract Background There is uncertainty around the optimal surveillance of head and neck cancer patients after the primary curative treatment. This study aims at assessing the cost-effectiveness of a post-treatment programme of frequent radiological assessments (maximal approach) compared with a symptom-driven surveillance (minimal approach). Materials and methods A decision-analytic Markov model is developed to assess the cost utility of two alternative follow-up programmes with a lifetime horizon. The two interventions differ in the number of radiological assessments (i.e. magnetic resonance imaging, computed tomography and positron-emission tomography) performed over a 5-year period. Clinical and utility parameters are derived from published and unpublished literature and expert opinion. The cost analysis is conducted from the perspective of a major Italian region's health care system. Cost-effectiveness results are expressed as incremental cost per life year gained (LYG) and per quality-adjusted life year (QALY) and checked against a cost-effectiveness threshold of €25,000–40,000 per QALY. One-way, two-way and probabilistic sensitivity analyses are carried out. Results In the base-case analysis, an intensive programme of radiological investigations leads to 0.10 additional QALYs (0.15 LYG) and an increase in costs of €1903 per patient compared with those of a minimal option, resulting in an incremental cost of €19,951/QALY gained (€13,123/LYG). In probabilistic sensitivity analysis, 72% of the results lie below the €40,000 threshold (55% below €25,000). Conclusions An intensive post-treatment follow-up with scheduled radiological assessments over time might be cost-effective compared with symptom-driven surveillance in head and neck cancer patients. Further research is needed to check these results in empirical studies or real-world settings. Highlights The optimal number of examinations in head and neck cancer follow-up is uncertain. A randomised controlled trial is currently ongoing in Italy. Frequent radiological investigation is compared with symptom-driven surveillance. A Markov model is developed to estimate the cost utility of the two programmes. The more intensive follow-up appears cost-effective at around €20,000 per quality-adjusted life year.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

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