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  • American Society of Clinical Oncology (ASCO)  (6)
  • 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
    Online Resource
    Online Resource
    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
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  • 3
    Online Resource
    Online Resource
    Validation of a Gene Expression Signature for Assessment of Lymph Node Metastasis in Oral Squamous Cell Carcinoma
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 33 ( 2012-11-20), p. 4104-4110
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 33 ( 2012-11-20), p. 4104-4110
    Abstract: Current assessment of lymph node metastasis in patients with head and neck squamous cell carcinoma is not accurate enough to prevent overtreatment. The aim of this study was validation of a gene expression signature for distinguishing metastasizing (N+) from nonmetastasizing (N0) squamous cell carcinoma of the oral cavity (OSCC) and oropharynx (OPSCC) in a large multicenter cohort, using a diagnostic DNA microarray in a Clinical Laboratory Improvement Amendments/International Organization for Standardization–approved laboratory. Methods A multigene signature, previously reported as predictive for the presence of lymph node metastases in OSCC and OPSCC, was first re-evaluated and trained on 94 samples using generic, whole-genome, DNA microarrays. Signature genes were then transferred to a dedicated diagnostic microarray using the same technology platform. Additional samples (n = 222) were collected from all head and neck oncologic centers in the Netherlands and analyzed with the diagnostic microarray. Human papillomavirus status was determined by real-time quantitative polymerase chain reaction. Results The negative predictive value (NPV) of the diagnostic signature on the entire validation cohort (n = 222) was 72%. The signature performed well on the most relevant subset of early-stage (cT1-T2N0) OSCC (n = 101), with an NPV of 89%. Conclusion Combining current clinical assessment with the expression signature would decrease the rate of undetected nodal metastases from 28% to 11% in early-stage OSCC. This should be sufficient to enable clinicians to refrain from elective neck treatment. A new clinical decision model that incorporates the expression signature is therefore proposed for testing in a prospective study, which could substantially improve treatment for this group of patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2011.40.4509
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    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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  • 5
    Online Resource
    Online Resource
    Adjuvant Chemotherapy in Patients With Stage I-IIIA Large-Cell Neuroendocrine Carcinoma: Should a Different Approach Be Applied Than for Small-Cell Lung Cancer?
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 13 ( 2021-05-01), p. 1508-1509
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 13 ( 2021-05-01), p. 1508-1509
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.20.03598
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 6
    Online Resource
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    Prediction of local recurrence in oral squamous cell carcinoma using immune markers.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e18538-e18538
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e18538-e18538
    Abstract: e18538 Background: The local recurrence rate of oral squamous cell carcinomas (OSCC) hardly decreases despite the best possible treatment. Partly, this is caused by the presence of (pre)malignant cells in the surrounding tissue, which can develop into a new malignancy in time. Histological recognition of these cells in resection margins appears to be difficult during routine practice. The aim of this study was to determine whether or not the presence of immune cells in OSCC resection margins may predict the development of a recurrence in these patients. Methods: Thirty-four patients with firstly diagnosed, radically resected primary OSCC with histopathological confirmed tumor-free margins (treated between 1993 and 2003) were included. Nine patients out of the 34 patient developed a locoregional recurrence within 5 years. Formalin-fixed paraffin-embedded tissue sections of 34 resection margins were subjected to immunohistochemistry for CD45, CD3, CD4, CD8, PD-L1 and PD-1 expression in immune cells, after which a quantitative analysis of the largerst distribution of CD45-, CD3-, CD4-, CD8-, PD-L1 and PD-1 positive lymphocytes on each resection margin has been photographed. The highly immunostained surface in relation to the total surface has been measured up to 100μm below the squamous epithelium. This analysis has been performed using QWin software (Leica). All data were analyzed using GraphPad Prism (version 7.05 for Windows, GraphPad Software, La Jolla California USA, www.graphpad.com). Results: Only CD3 and CD8 had a moderate correlation (Spearman = 0.68). A high expression of CD45 (≥7.7% ) and CD4 (≥5,4%) was strongly correlated with a worse disease-free survival (p = 0.0054 and p 〈 0.001, respectively), as was a low CD3 expression (≤5,9%) (p = 0.0211). PD-L1 and PD-1 expression analysis did not show a significant association with recurrence risk. Conclusions: A high amount of CD45-, and CD4- and a low amount of CD3-positive immune cells in OSCC resection margins may predict local recurrence.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e18538
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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