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  • American Society of Clinical Oncology (ASCO)  (10)
  • 1
    Online Resource
    Online Resource
    A phase II study of everolimus in patients with aggressive RAI refractory (RAIR) thyroid cancer (TC).
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 6023-6023
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 6023-6023
    Abstract: 6023 Background: We present results of an open label phase II study of the mTOR inhibitor Everolimus in patients (pts) with RAIR TC. Methods: Pts with metastatic, incurable RAIR TC who had shown radiographic progression within 6 months prior to enrollment received Everolimus 10mg orally once daily. Responses were monitored by CT's every two months. The primary endpoint was progression free survival. Sequential biopsies were obtained in selected pts. Results: Enrollment to the differentiated TC (DTC) cohort finished in Jan 2013 and included 33 pts, among them 11 with Hurthle cell TC. Exploratory cohorts enrolled 10 pts with medullary [MTC] and 5 with anaplastic [ATC] with 2 added openings remaining for ATC. For the DTC cohort, median time on study to date is 10 months (mo) ( 〈 1-23+). 31 pts are evaluable at this time. PFS in the DTC cohort by Kaplan-Meier (K-M) analysis is 16.0 mo (95%CI 10-NR). Currently, disease stability for 6 and 12 mo or more was achieved in 18 and 10/31 pts, respectively, 11 pts remain on study. Median OS was not reached but 1 year survival by K-M analysis was 76%. One pt achieved a PR. 3 pts with DTC underwent sequential biopsies which revealed activation of autophagy while markers for apoptosis were not detected. Among 10 MTC pts, one achieved a PR and 9 pts had stable disease for 6 mo or more (6-33+). Among 5 ATC pts, 3 progressed, one has ongoing disease stability for 5 mo. One patient achieved a complete response that lasted for 18 mo and whole exome sequencing revealed somatic loss of function mutation affecting the Tuberous Sclerosis 2 (TSC2) protein, a negative regulator of mTOR activity [TSC2 (Q1178*) and FLCN (R17fs)]. Most common treatment-related adverse events were as anticipated and included fatigue, stomatitis and infections. Grade (gr) 3 events included infection 5, weight loss 3, leukopenia 3, thrombocytopenia 3, fatigue 3, hypophosphatemia 2, stomatitis 2, pneumonitis 1 and thrombosis 1pts. One pt had gr 4 hypercholesterinemia and one pt had gr 4 leukopenia. Conclusions: Everolimus has significant anti-tumor activity in pts with advanced TC. Activation of autophagy could account for high rate of disease stability. Sequencing may identify mechanistic basis and predictive markers for treatment response. Clinical trial information: NCT00936858.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.6023
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 2
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    International Medullary Thyroid Carcinoma Grading System: A Validated Grading System for Medullary Thyroid Carcinoma
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 1 ( 2022-01-01), p. 96-104
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 1 ( 2022-01-01), p. 96-104
    Abstract: Medullary thyroid carcinoma (MTC) is an aggressive neuroendocrine tumor (NET) arising from the calcitonin-producing C cells. Unlike other NETs, there is no widely accepted pathologic grading scheme. In 2020, two groups separately developed slightly different schemes (the Memorial Sloan Kettering Cancer Center and Sydney grade) on the basis of proliferative activity (mitotic index and/or Ki67 proliferative index) and tumor necrosis. Building on this work, we sought to unify and validate an internationally accepted grading scheme for MTC. PATIENTS AND METHODS Tumor tissue from 327 patients with MTC from five centers across the United States, Europe, and Australia were reviewed for mitotic activity, Ki67 proliferative index, and necrosis using uniform criteria and blinded to other clinicopathologic features. After reviewing different cutoffs, a two-tiered consensus grading system was developed. High-grade MTCs were defined as tumors with at least one of the following features: mitotic index ≥ 5 per 2 mm 2 , Ki67 proliferative index ≥ 5%, or tumor necrosis. RESULTS Eighty-one (24.8%) MTCs were high-grade using this scheme. In multivariate analysis, these patients demonstrated decreased overall (hazard ratio [HR] = 11.490; 95% CI, 3.118 to 32.333; P 〈 .001), disease-specific (HR = 8.491; 95% CI, 1.461 to 49.327; P = .017), distant metastasis-free (HR = 2.489; 95% CI, 1.178 to 5.261; P = .017), and locoregional recurrence-free (HR = 2.114; 95% CI, 1.065 to 4.193; P = .032) survivals. This prognostic power was maintained in subgroup analyses of cohorts from each of the five centers. CONCLUSION This simple two-tiered international grading system is a powerful predictor of adverse outcomes in MTC. As it is based solely on morphologic assessment in conjunction with Ki67 immunohistochemistry, it brings the grading of MTCs in line with other NETs and can be readily applied in routine practice. We therefore recommend grading of MTCs on the basis of mitotic count, Ki67 proliferative index, and tumor necrosis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.21.01329
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Everolimus in anaplastic thyroid cancer: A case series.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. e18112-e18112
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e18112-e18112
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.e18112
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Evaluating the frequency and functional consequences of epigenetic mutations on outcome derived from urothelial tumor sequencing in non-muscle invasive bladder cancer (NMIBC).
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. e15519-e15519
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. e15519-e15519
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.15_suppl.e15519
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Genomic landscape of high-grade T1 micropapillary bladder tumors.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 7_suppl ( 2015-03-01), p. 299-299
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 7_suppl ( 2015-03-01), p. 299-299
    Abstract: 299 Background: The genomic landscape of high-grade T1 micropapillary bladder tumors (HGT1micropap) is unknown. Clinically, micropapillary bladder cancer is an aggressive and possibly lethal disease. Our main objective was to assess the genomic landscape of HGT1micropap through identifying mutations, insertions/deletions (indels), translocations, and copy number variations (CNVs). Methods: We prospectively identified nine HGT1micropap with 45.4 months of median follow up. Patients were treated in a uniform manner using TUR, BCG, and appropriate follow up. We performed whole exome sequencing using Ilumina Exome _v5 plus translocation. Mutations and indels were called using the Firehose pipeline. CNVs were called using ExomeCNV. We examined the mutational landscape and compared the genomic alterations to TCGA ( 〉 T2, n=131) 2 and publicly available data on non-muscle invasive bladder tumors (Ta/T1, n=37) 1 . Results: Within the HGT1micropap, mutations on TP53, KMT2D, TSC1, and ATM were suggested to occur more frequently compared to the NMIBC control group 1 . FGFR3 was seen at the expected frequency for NMIBC. The mutations of interest are presented in Table 1 with the percentage seen in the other cohorts. Of interest, TSC1 was seen in higher frequency in micropapillary than in the NMIBC or the TCGA cohort 2 . We did not see any patterns between CNVs and mutations. We also saw two patients with severe chromothripsis. 3 patients had loss of chromosome 9 or 9q without any other severe chromosome alterations. CNV alterations will be presented and compared to MIBC. Conclusions: In this preliminary analysis, our HGT1micropap, showed a mutational landscape more similar to MIBC compared to NMIBC bladder landscape. We did not find any clear driver of the micropapillary histology at the exome level in this limited sample of patient, which may indicate that tumor heterogeneity or epigentic changes may be driving this aggressive phenotype. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.7_suppl.299
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 6
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    A phase II study of nivolumab (N) plus ipilimumab (I) in radioidine refractory differentiated thyroid cancer (RAIR DTC) with exploratory cohorts in anaplastic (ATC) and medullary thyroid cancer (MTC).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 6513-6513
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 6513-6513
    Abstract: 6513 Background: Treatment options for aggressive TC are limited. Pre-clinical data suggests efficacy of CTLA-4 plus PD-1 blockade in aggressive RAIR TC. Methods: This investigator initiated phase II study tested N (3mg/kg every 2 weeks) plus I (1mg/kg every 6 weeks) until disease progression or completion of 24 mo of treatment in RAIR differentiated TC including poorly differentiated TC (PDTC) with exploratory cohorts in anaplastic (ATC) and medullary TC (MTC). Radiographic response rate by RECIST v1.1 (CR+PR) was primary endpoint. At least 6 pts with disease response among n=32 DTC provided 84% power to distinguish between a 10% and a 25% RR (one-sided 9% binomial test). Results: Accrual is complete with n=32 patients with DTC, 10 with ATC and 7 with MTC enrolled between October 2017 and May 2019. Thirty-two DTC included: n=17 papillary, n=7 Hurthle, n=4 follicular TC, n=4 PDTC. Among n=49, median (range) age was 65 (30-88), 51% (25/49) were female. To date, in DTC, 3/32 achieved a PR (n=2 Hurthle and n=1 PDTC), 9.4% RR (.95CI:2%-25%). One near complete response has been observed. Among pts w ATC, 3/ 10 profound PR by RECIST occurred (30% RR, .95CI: 7%-65%). Among them, two remain without clear evidence of disease at 26 and 13 mo after treatment start. No PR's were observed in MTC. Most frequent grade 3-4 TRAEs were as expected and included increased lipase (n=8), increased serum amylase (n=4). There was an unexpected number of treatment related adrenal insufficiency (AI) (n=4) which was associated with long PFS (range 10.1—16.4+mo). Conclusions: N+I appears to have considerable activity in ATC. In unselected RAIR DTC, activity was low but responses were seen in PDTC and Hurthle cell TC. Exceptional responses with prolonged remissions were observed. Clinical trial information: NCT03246958 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.6513
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Clinicopathologic Characteristics of Malignant Mesotheliomas Arising in Patients With a History of Radiation for Hodgkin and Non-Hodgkin Lymphoma
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 36 ( 2013-12-20), p. 4544-4549
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 36 ( 2013-12-20), p. 4544-4549
    Abstract: Studies have reported an association between pleural diffuse malignant mesothelioma (PDMM) and chest radiation for lymphoma. The clinicopathologic characteristics of malignant mesotheliomas arising in these patients have not been established. Patients and Methods We studied 1,618 consecutive patients diagnosed with pleural PDMM from July 1993 to February 2008 and identified patients with a history of radiation for Hodgkin and non-Hodgkin lymphoma. We evaluated the histology in the surgical resection specimens and compared clinicopathologic features with overall survival. Results We identified 22 patients who developed PDMM after chest radiation as part of their treatment for lymphoma (mean latency time, 21.4 years; 95% CI, 17.0 to 25.8 years). Asbestos bodies in lymphoma-associated PDMM were lower than in asbestos-associated PDMM (median count, 15 v 325 bodies, respectively; P 〈 .001) and similar to an unexposed control group (median count, 15 v 10 bodies, respectively; P = .6). Seventeen lymphoma-associated PDMMs (77%) were epithelioid and five (23%) were biphasic. Seven PDMMs (32%) had unusual histologies (pleomorphic, myxoid, clear cell, and signet ring cell). Patients with lymphoma-associated PDMM were younger than patients with asbestos-associated PDMM (median age, 45 v 64 years, respectively; P 〈 .001) and had a significantly longer overall survival time (median, 32.5 v 12.7 months, respectively; P = .018). In multivariate analysis, independent favorable predictors for overall survival were history of prior radiation (P = .022), female sex (P 〈 .001), age ≤ 65 years (P = .005), cytoreductive surgery (P 〈 .001), and epithelioid histology (P 〈 .001). Conclusion Patients with lymphoma-associated PDMM are likely to have unusual histologic features, are significantly younger, and seem to have a longer overall survival compared with patients with asbestos-associated PDMM.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2013.49.9616
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
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  • 8
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    Mutational Footprint of Platinum Chemotherapy in a Secondary Thyroid Cancer
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  JCO Precision Oncology , No. 6 ( 2022-08)
    Details
    In: JCO Precision Oncology, American Society of Clinical Oncology (ASCO), , No. 6 ( 2022-08)
    Type of Medium: Online Resource
    ISSN: 2473-4284
    URL: Article
    DOI: 10.1200/PO.22.00183
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 9
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    Impact of pure versus mixed metastatic urothelial carcinoma (mUC) histology on response with immune checkpoint inhibitors (ICIs).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 7_suppl ( 2019-03-01), p. 479-479
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 479-479
    Abstract: 479 Background: PD1/PD-L1 inhibitors have been evaluated in trials enrolling patients (pts) with pure urothelial or mixed urothelial histology containing non-urothelial components. However, any differential impact of pure vs. mixed urothelial histology on ICI benefit is unclear. We conducted a retrospective study to evaluate the impact of pure vs. mixed urothelial carcinoma histology on outcomes with ICIs in pts with metastatic urothelial carcinoma (mUC). Methods: We obtained data from 120 pts with mUC from a single institution (DFCI) who received ICI therapy. Demographic, clinical variables and outcomes (overall response rate [ORR], overall survival [OS] ) were collected. Histology was reviewed at DFCI for all pts and recorded as pure urothelial if only urothelial carcinoma was seen or mixed urothelial if components of any other histology were observed in addition to urothelial. A Cox regression analysis was done to study the association of prognostic variables and histology with objective response. Results: Data was obtained from 120 pts, of whom 110 (91.7%) received a single agent PD1/PD-L1 inhibitor (pembrolizumab=58, atezolizumab=52, nivolumab=4, nivolumab + ipilimumab=3, nivolumab + vaccine=2, durvalumab+tremelimumab=1). The median age was 66, 70.8% were male and 72.5% had received prior chemotherapy. 79 (65.8%) tumors originated from the bladder, 39 (32.5%) from the upper tract, 2 (1.67%) had unknown site of origin. 91 (76.6%) had pure urothelial and 28 (23.3%) had mixed urothelial histology. On univariable analysis, pure vs. mixed urothelial histology was not associated with response (HR 1.52 [95% CI 0.59-3.98, p=0.39]). On multivariable analysis, upper tract vs. bladder primary (HR 3.06 [95% CI 1.10-8.49] , p=0.032) and higher blood neutrophil to lymphocyte ratio (HR 0.35 [95% CI 0.17-0.72], p=0.004) were associated with lower response rate. Conclusions: In this hypothesis-generating study, pure vs. mixed urothelial carcinoma histology did not appear to significantly impact response to ICI therapy for mUC. The impact of proportion of non-urothelial histology, pure non-urothelial histology and site of primary on response warrants further study.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.7_suppl.479
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Squamous cell carcinoma of the oral cavity (SCCOC) in young patients: The Dana Farber Cancer Institute experience.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 6054-6054
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 6054-6054
    Abstract: 6054 Background: Young patients (≤ age 45) with SCCOC and limited tobacco and alcohol exposure represent a distinct clinical entity with a poor prognosis. These patients are poorly characterized. We report our institution’s experience treating these patients over the past decade. Methods: Patients ≤ 45 years with SCCOC treated between 2001 and 2012 were identified retrospectively. Patient characteristics and treatment were recorded. Results: A total of 99 patients were identified (34 F and 65 M). Median age at diagnosis was 34 and 38 years, respectively (range 14 to 45 years). Thirty one (91.2%) women were never or former smokers with fewer than 10 pack-years, as compared with 50 (76.9%) men (p = 0.07). In women, 33 (97.1%) reported minimal to no alcohol use, compared with 52 (80%) men (p = 0.02). Oral tongue was the primary site in the majority of patients (30 F, 58 M). Surgical resection was the primary treatment modality (30, 88.2% F vs. 44, 68% M). Post-op radiation or chemoradiation was applied depending on stage and pathological findings. Stage: 53/99 (53.5%) presented with stage I or II disease and 46/99 (46.5%) had stage III or IV disease. Males on average had more advanced stage disease at presentation (33/65, 50.8%). Four of 7 women and 4 out of 18 men tested positive for human papilloma virus (HPV). Seven women (20.6%) and 13 (20%) men demonstrated evidence of local or locoregional recurrence with a median time to recurrence of 5 years and 0.67 years (range 1-10 and 0.08-11), respectively. Second primaries were rare (2, 5.88% F vs. 0, 0% M). Two women (5.9%) and 9 men (13.9%) died from recurrent disease. Overall, 4 (30.8%) women with stage III, IV disease demonstrated recurrence vs. 6 (18.2%) men (p = 0.35). Conclusions: In our experience, young patients with SCCOC have high cure rates that do not appear to be inferior to other sites in the head and neck area. Men and women are equally affected. Further clinical and genomic characterization for this group of patients is warranted.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.6054
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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