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  • American Society of Clinical Oncology (ASCO)  (3)
  • Thunnissen, Erik  (3)
  • 1
    Online Resource
    Online Resource
    Genetic subtypes of large cell neuroendocrine carcinoma (LCNEC) to predict response to chemotherapy.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 9061-9061
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 9061-9061
    Abstract: 9061 Background: To treat LCNEC with non-small cell lung carcinoma type chemotherapy (NSCLC-ct, i.e. gemcitabine/taxanes or pemetrexed) or small cell lung carcinoma type (SCLC-ct, i.e. platinum-etoposide) is subject of debate. Molecular studies have identified two mutually exclusive subtypes in LCNEC, the co-mutated TP53 and RB1and the STK11/ KEAP1 (predominantly RB1 wildtype( wt )) group. We investigated if overall survival (OS) and progression free survival (PFS) correlates with targeted next-generation sequencing (TNGS) results in LCNEC treated with NSCLC-ct or SCLC-ct. Methods: For this population based retrospective cohort study all diagnoses of stage IV ct treated high grade neuroendocrine carcinomas (NEC, not being SCLC) were retrieved from the Netherlands Cancer Registry and Pathology Registry (PALGA) (2003-2012). Panel-consensus pathology revision of original tumor slides was performed on (N = 230) and TNGS for genes TP53, RB1, STK11 and KEAP1 analyzed with a multi-sample variant caller (Needlestack). Results: LCNEC was consensus diagnosed in 146/230 and 77 passed quality control for TNGS. Mean coverage was 2832x, a mutation( mt ) in TP53 was present in 87%, RB1 mt in 46%, STK11 mt in 13% and KEAP1 mt in 18% of sequenced LCNEC. RB1 was co-altered with TP53 in 94% of LCNEC; mutually exclusive to STK11 mt (100%) but not KEAP1 mt (57%). NSCLC-ct or SCLC-ct was specified in 92% of patients and RB1 wt LCNEC treated with NSCLC-ct (n = 22) showed a trend to better OS compared to SCLC-ct (n = 13) (8.5 months (95% confidence interval (CI): [6.3-10.6]) vs. 5.8 [5.5-6.1] months, p = 0.055). Due to reported resistance in NECs we analyzed NSCLC-ct without pemetrexed-ct; OS was significantly longer for NSCLC-ct (n = 15) compared to SCLC-ct (9.6 [7.7-11.6] vs. 5.8 [5.5-6.1] months, p = 0.026). PFS of RB1 wt NSCLC-ct treated patients was significantly longer than SCLC-ct (p = 0.044), without pemetrexed (p = 0.018). In patients with RB1 mt LCNEC OS/PFS was not significantly different for NSCLC-ct vs. SCLC-ct. Conclusions: In LCNEC with RB1 wt , NSCLC-ct correlates with a more favorable outcome compared to SCLC-ct. However, RB1 mt LCNEC treated with NSCLC-ct do similarly worse as SCLC-ct. Prospective studies should be initiated.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.9061
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Prevalence and Clinical Outcomes for Patients With ALK-Positive Resected Stage I to III Adenocarcinoma: Results From the European Thoracic Oncology Platform Lungscape Project
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 25 ( 2014-09-01), p. 2780-2787
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 25 ( 2014-09-01), p. 2780-2787
    Abstract: The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non–small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population. Methods Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment. Results Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS). Conclusion In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2013.54.5921
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 3
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    Online Resource
    Prevalence and clinical correlation of programmed cell death 1 ligand (PD-L1) expression in patients with resected non-small cell lung cancer (NSCLC): Results from the European Thoracic Oncology Platform (ETOP) Lungscape cohort.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 8516-8516
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 8516-8516
    Abstract: 8516 Background: Conflicting data exists on the potential prognostic impact of PD-L1 expression in NSCLC. The Lungscape project, a fully annotated large biobank of resected stage I-III NSCLC, allows detailed analysis of this issue. Methods: Prevalence of PD-L1 positivity and its association with clinicopathological characteristics and patient outcome - Relapse-free Survival (RFS), Time-to-Relapse (TTR) and Overall Survival (OS) - was explored in the ETOP Lungscape cohort. PD-L1 expression was assessed on tissue microarrays (TMAs) using the DAKO 28-8 immunohistochemistry assay. Positivity cut-off points of ≥1%, 5% and 50% for neoplastic cell membrane staining were considered. Results: PD-L1 data were available for 2182 patients, from 15 ETOP centers, with median follow-up 4.8 years; 1191 patients still alive; median age 66 years; 64% male, 32/54/11% for current/former/never smokers; 49/29/22% for stages I/II/III; 51/42/4/3% adenocarcinomas (AC)/squamous cell (SCC) /large cell and sarcomatoid (LCS)/other. Median RFS/TTR/OS were 53/99/69 months (AC: 52/84/72, SCC: 54/not reached/64; and LSC 52/103/74). PD-L1 prevalence with 1% cut-off was, overall: 43%, 95% confidence interval (95%CI): 41-46; (AC: 42%, 95%CI: 39-46; SCC: 44%, 95%CI: 40-47; and LCS: 53%, 95%CI: 42-65), while for 5% threshold, prevalence was 34%, 95%CI: 32-36. PD-L1 1% positivity was a significant predictor only for AC: HR RFS: + vs - = 0.82; 95%CI: 0.69-0.97, HR TTR: + vs - = 0.83; 95%CI: 0.68-1.01, HR OS: + vs - = 0.83; 95%CI: 0.69-1.01 (adjusted p = 0.024, 0.064, 0.063 respectively). This effect is found also for the 5% cut-off, and preserved in the overall model including all histologies. Using the 50% cut-off, PD-L1 positivity was detected in 17% of patients; 95%CI: 15-18, but was no longer a significant predictor of outcome, overall and by histology type. Conclusions: PD-L1 positivity (1% and 5% cut-offs) was present in more than one third of resected NSCLC and was associated with a better prognosis for AC patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.8516
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
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