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  • 1
    Online Resource
    Online Resource
    Potential role of circulating tumor DNA (ctDNA) in the early diagnosis and post-operative management of localised pancreatic cancer.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 4101-4101
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 4101-4101
    Abstract: 4101 Background: Pancreatic cancer remains a devastating disease, with the diagnosis typically being made late. ctDNA has shown promise as a screening test for various tumor types. The detection of ctDNA post curative intent surgery has been associated with a high risk of recurrence in multiple solid tumors. We explored the potential of ctDNA to improve pancreatic cancer outcomes. Methods: Data from separate US and Australian series were combined. Plasma samples were collected prior to surgery in both studies and post-operative samples were collected in Australia from cases undergoing curative intent surgery. Clinicians were blinded to ctDNA results and adjuvant therapy was at clinician discretion. Tissue samples from both series were analyzed at Johns Hopkins University. Next generation sequencing was used to search for somatic KRAS mutations in the primary tumors and in cell-free DNA in the plasma. Clinico-pathologic, treatment and outcome data were collected. Results: 119 pts had a ctDNA sample at diagnosis (median age 67 years, 56.3% male). Sixty six pts (55.5 %) had detectable ctDNA, including 3/7 (42.9%) with stage I disease, 54/99 (54.5%) with stage II disease, 4/8 (50%) with stage III disease and 5/5 (100%) with metastases. Specific codon 12 KRAS (G12D, G12V or G12R) mutations were identified in the tumor tissue of 12/16 (75%) patients who had a ctDNA sample collected post-surgery. At a median follow-up of 15.2 months, 7/12 (58.3%) pts had recurred, including 3/8 (37.5%) with no detectable ctDNA and 4/4 (100%) with detectable ctDNA post-surgery (HR 4.9, p = 0.04). Detectable ctDNA post-surgery was significantly associated with poor overall survival (HR 6.93, p = 0.006), with a median of 8 months for pts with detectable ctDNA. Conclusions: ctDNA shows promise as a pancreatic cancer screening test, being detectable in a high proportion of pts with early stage disease. The detection of ctDNA post operatively predicts a very high risk of recurrence. The clinical utility of ctDNA to guide adjuvant therapy decision making, and its potential as a real-time marker of treatment effect, are being explored in further studies. Clinical trial information: ACTRN12612000763842.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.4101
    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
    Circulating tumor DNA as a prognostic biomarker in early stage pancreatic cancer.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. e16206-e16206
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e16206-e16206
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.e16206
    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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  • 3
    Online Resource
    Online Resource
    Phase II study of GM-CSF secreting allogeneic pancreatic cancer vaccine (GVAX) with PD-1 blockade antibody and stereotactic body radiation therapy (SBRT) for locally advanced pancreas cancer (LAPC).
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. TPS4154-TPS4154
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. TPS4154-TPS4154
    Abstract: TPS4154 Background: Optimal treatment strategy beyond systemic chemotherapy for LAPC remains undefined. SBRT improves local control, but distant metastasis free survival (DMFS) is only 7.7 months. Checkpoint inhibitors are poor monotherapies in pancreas cancer, but may be primed by SBRT via absocopal effect and GVAX, which induces novel lymphoid infiltrates and increased effector T-cells in tumor microenvironment. Methods: This is a single-arm, single-institution, open-label study for pts with LAPC. Eligibility: surgically unresectable LAPC, predominant adenocarcinoma at diagnosis, with ECOG 0-1, who remain metastases free after 4-8 cycles of FOLFIRINOX or gemcitabine/abraxane based-chemotherapy. Exclusion: those off chemotherapy 〉 49 days prior to study treatment, prior immunotherapy, active immunosuppressive use, autoimmune disease, HIV, HBV, or HCV infection, and non-oncology vaccines within 28 days of study treatment. Pts receive cyclophosphamide (200mg/m2 IV) and pembrolizumab (200mg IV) on day 1, followed by GVAX (six intradermal injections) on day 2 every three weeks for two cycles, with cycle 2 initiating concurrently with five days of SBRT. If non-metastatic, pts undergo surgical resection, nano-knife, or EUS guided biopsy (if non-surgical). Pts receive two further cycles of chemotherapy, and if remain free of metastases, receive q3 week cyclophosphamide, pembrolizumab, and GVAX for six cycles, then are monitored for two years. The primary endpoint is DMFS. Secondary endpoints include overall survival, surgical resectability, pathologic response, quality of life, and toxicity. Exploratory objectives of peripheral antigen specific t-cell responses, and changes in immune parameters of tumor microenvironment. 11 of 54 pts have been enrolled since July 2016. Clinical trial information: NCT02648282.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.TPS4154
    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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  • 4
    Online Resource
    Online Resource
    Association of ALDH-expressing cancer stem cells with survival in patients with resected pancreatic adenocarcinoma treated with adjuvant chemoradiation.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 3_suppl ( 2014-01-20), p. 262-262
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 262-262
    Abstract: 262 Background: We and others have identified aldehyde dehydrogenase (ALDH) activity as a marker of pancreatic cancer stem cells (or tumor-initiating cells). The presence of cancer stem cells (CSCs) has been associated with decreased survival and treatment resistance in pancreatic adenocarcinoma. We investigate the role of ALDH expression in predicting survival and patterns of disease recurrence in patients treated with chemoradiation (CRT) following pancreatectomy. Methods: Tissue microarrays using surgical specimens from 1998 to 2002 were stained for ALDH1 and scored as ALDH-positive or ALDH-negative by two expert pancreatic pathologists blinded to patient outcomes. Physician documentation and radiology reports were used to determine follow-up information. Time to local failure (TLF), time to distant metastases (TDM), progression-free survival (PFS), and overall survival (OS) were analyzed using SPSS software. Results: Previously we found that ALDH expression was associated with worse OS in a cohort of 269 patients with resected pancreatic adenocarcinoma (Rasheed, JNCI 2009). From this cohort, adjuvant treatment information was available for 87 patients with ALDH-negative tumors (48.6%) and 41 patients with ALDH-positive tumors (45.6%). In patients treated with adjuvant CRT, median overall survival was superior in the ALDH-negative cohort vs. the ALDH-positive cohort, 26.3 months vs. 18.2 months (p=0.011). Further, in patients treated with adjuvant CRT, ALDH-negative patients had statistically greater TLF, TDM, and PFS than their ALDH-positive counterparts (see table). On multivariate analysis, ALDH positive tumor staining (HR 1.94, p=0.004) and tumor grade (HR 1.54, p=0.041) predicted lower OS, and ALDH positive tumor staining (HR 1.83, p=0.008), tumor grade (HR 1.52, p=0.038), and tumor size 〉 3 cm (HR 1.65, p=0.023) predicted decreased PFS. Conclusions: This study suggests that adjuvant CRT improves TLF, TDM, PFS, and OS in patients with localized pancreatic adenocarcinoma not enriched with ALDH-expressing CSCs. Laboratory studies will help elucidate the mechanisms of treatment resistance in ALDH expressing CSCs.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.3_suppl.262
    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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  • 5
    Online Resource
    Online Resource
    Stereotactic body radiation therapy for pancreatic cancer: Single institutional experience.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 3_suppl ( 2014-01-20), p. 328-328
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 328-328
    Abstract: 328 Background: Stereotactic Body Radiation Therapy (SBRT) is emerging as a possible standard treatment for pancreatic cancer; however, there is limited data to support its efficacy. This study reviews our institution’s experience using SBRT in the treatment of pancreatic cancer (PCA). Methods: Charts of all PCA patients receiving SBRT from January 2010 to June 2013 were retrospectively reviewed. The primary end points were overall survival (OS) and tumor response assessed by RECIST criteria. 95% of the PTV (GTV + 2-3 mm) received a total dose of 20-33 Gy in five fractions (4-6.6 Gy/fraction), with up to 20% heterogeneity allowed. Pre- and post-SBRT chemotherapy regimens included gemcitabine, cisplatin, FOLFIRINOX, 5-FU or paclitaxel. Results: 84 patients received SBRT, with a median follow-up time of 15.3 months. Median age was 66.5 years, 57.1% were male and 65.5% had head tumors. 66 patients received definitive SBRT for locally advanced or borderline resectable PCA, 4 patients were treated with adjuvant SBRT, and 14 received SBRT for treatment of recurrent disease. Median OS from the date of diagnosis for patients receiving definitive radiation was 17.8 mos (95% CI 14.9-20.9).For recurrent patients the median OS from first day of SBRT was 11.8 mos (95%CI 8.3-15.3). In the definitive SBRT group, among patients who were alive and had follow-up scans, the 6 and 12 month local control rate (stable or partial response) based on RECIST criteria was 84.6% and 81.8%, respectively. Five patients underwent surgery following SBRT and all had negative resection margins. Acute toxicity was minimal with most experiencing grade 1 or 2 fatigue and no grade 3/4 acute toxicity. Late grade 3/4 GI toxicity was seen in 5% (4/84) and 1 patient had a grade 5 GI bleed due to direct tumor invasion into the duodenum. Conclusions: Our early results using SBRT in the definitive and recurrent settings show favorable local control, toxicity, and survival when compared to historical outcomes using chemoradiation. Acute and late toxicity was minimal however the optimal dose and fractionation as well as normal tissue dose constraints need to be determined. Integration of SBRT with more aggressive chemotherapy may result in improved outcomes in patients with PCA.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.3_suppl.328
    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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  • 6
    Online Resource
    Online Resource
    Hemoglobin-A1c level to predict for clinical outcomes in patients with pancreatic cancer.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 4039-4039
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 4039-4039
    Abstract: 4039 Background: An association between diabetes mellitus (DM) and pancreatic ductal adenocarcinoma (PDA) has long been recognized. While long-standing DM may be a risk factor for developing PDA, new-onset DM may be a manifestation of the cancer. Here we assess the role of an objective and quantifiable measure of glucose intolerance, hemoglobin-A1c (HbA1c), in predicting clinical outcomes in PDA. Methods: HbA1c values were prospectively collected on 656 consecutive patients presenting to the Johns Hopkins Pancreas Multidisciplinary Cancer Clinic from 2009-2012. Patients were diagnosed with benign pancreatic disease (BPD) or biopsy-confirmed resectable (R), borderline/locally advanced (BL), or metastatic (M) PDA. Patients with prior treatment for PDA or a history of DM greater than a 1-year were excluded. Univariate Cox regression analyses and multivariable proportional hazards models were used to identify poor prognostic factors for overall survival. Results: Of 284 patients included, 44 had benign disease, 62 R-PDA, 115 BL-PDA, and 63 M-PDA. Patients with malignant disease (R-, BL-, and M-PDA) collectively had higher HbA1c values on average at presentation than patients with BPD (6.1% vs. 5.6%, p 〈 0.001). There was a trend towards higher HbA1c at presentation in patients with advanced PDA (BL and M) compared to patients with R-PDA (6.2% vs. 5.9%, p=0.100); moreover, the proportion of patients with HbA1c levels in the diabetic range ( 〉 6.4%) increased with more advanced stage of disease. Among patients with PDA (n=240), univariate analyses showed HbA1c≥6.5, age≥65, ECOG≥1, CA19-9 〉 90, tumor size 〉 3cm, and advanced stage to be significantly associated with inferior survival (all HR 〉 1, p 〈 0.05). After multivariate analysis with backward elimination, all of the above factors except for tumor size 〉 3cm remained in the model for inferior survival. Conclusions: HbA1c level at presentation appears to correlate with disease stage and, moreover, to predict for survival among all stages of PDA. Patients with PDA have significantly higher HbA1c levels at presentation than patients with BPD. This study highlights the potential utility of HbA1c as a screening tool and prognostic factor.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.4039
    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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  • 7
    Online Resource
    Online Resource
    Is successful resection following neoadjuvant radiation therapy for borderline resectable pancreatic cancer dependent on improved tumor-vessel relationships?
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 4057-4057
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 4057-4057
    Abstract: 4057 Background: Margin-negative (R0) surgical resection is the only potentially curative therapy for pancreatic cancer. For patients deemed borderline resectable (BL), neoadjuvant chemoradiotherapy (NRT) increases the likelihood of subsequent R0 resection and improves overall survival. Prognostic factors for achieving resection following NRT have yet to be clearly identified. Methods: Fifty consecutive patients with BL-PDAC evaluated by a multidisciplinary tumor board who received NRT from 2007-2012 were retrospectively identified. Computed tomography (CT) scans pre- and post-radiation and surgical specimens were centrally reviewed. Results: 29 patients underwent resection following NCRT, while 21 remained unresectable. Between the two groups, age, gender, mean RT dose, and proportion of pancreatic head tumors were not significantly different. Smaller tumor volume and lack of the following factors was associated with selection for resection: superior mesenteric/portal vein encasement (p=0.01), superior mesenteric artery involvement (p=0.02), ascites (p=0.01), and questionable/overt metastases (p=0.01). Notably, celiac artery involvement/encasement, common hepatic artery encasement, and percentage change in tumor volume were not significant predictors of resection (all p 〉 〉 0.05). Interestingly, tumor volume and degree of individual vessel involvement did not significantly change from scans before and after NCRT (all p 〉 〉 0.05). Median OS was 22.9 vs.13.0 months in resected and unresected patients, respectively (p 〈 0.001). Of resected patients, 93% had negative margins, 28% had positive nodes, 27% demonstrated 〈 10% viable tumor, and 12% had pathologic complete response at surgery. Dpc4 expression was retained in 68% of specimens with viable tumor. Conclusions: Although the apparent radiographic extent of vascular involvement does not change significantly after NRT, subsequent R0 resection rates are high, nodal involvement is low, and outcomes are similar to resected patients who receive adjuvant therapy. Resection attempts should not be deferred solely based on lack of improvement in tumor-vessel interactions.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.4057
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 8
    Online Resource
    Online Resource
    Variation in the surgical management of locally advanced pancreatic cancer.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 4122-4122
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 4122-4122
    Abstract: 4122 Background: Recent reports suggest patients with locally advanced pancreatic cancer (LAPC) may become candidates for curative resection following neoadjuvant therapy, with encouraging survival outcomes. Yet the optimal management approach for LAPC remains unclear. We sought to investigate surgeon preferences for the management of patients with LAPC. Methods: An extensive electronic survey was systematically distributed by email to an international cohort of pancreas surgeons. Data collected included surgeon practice characteristics, preferences for staging and management, and 6 clinical vignettes (with detailed videos of post-neoadjuvant arterial and venous imaging) to assess attitudes regarding eligibility for surgical exploration. Results: A total of 150 eligible responses were received from 4 continents. Median duration in practice was 12 years (IQR 6-20) and 75% respondents work in a university setting. Most (84%) are considered high volume, 33% offer a minimally-invasive approach, and 48% offer arterial resection in selected patients. A majority (70%) always recommend neoadjuvant chemotherapy, and 62% prefer FOLFIRINOX. Preferences for duration of neoadjuvant therapy varied widely: 39% prefer ≥2 months, 41% prefer ≥4 months, and 11% prefer 6 months or more. Forty-one percent frequently recommend neoadjuvant radiation, and 51% prefer standard chemoradiotherapy. Age ≥80 years and CA 19-9 of ≥1000 U/mL were commonly considered contraindications to exploration. In 5 clinical vignettes of LAPC, the proportion of respondents that would offer exploration following neoadjuvant varied extensively, from 15% to 54%. In a vignette of oligometastatic pancreatic liver metastases, 32% would offer exploration if a favorable biochemical and imaging response to therapy is observed. Conclusions: In an international cohort of high volume pancreas surgeons, there is substantial variation in attitudes regarding staging preferences and surgical management of LAPC. These results underscore the importance of coordinated multi-disciplinary care, and suggest an evolving concept of “resectability.” Patients and their oncologists should have a low threshold to consider a second opinion for the surgical management of LAPC, if desired.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.4122
    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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  • 9
    Online Resource
    Online Resource
    Novel score to predict outcome in resected pancreatic neuroendocrine tumors (pNET).
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. 4093-4093
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. 4093-4093
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.15_suppl.4093
    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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  • 10
    Online Resource
    Online Resource
    Detection of somatic mutations in fine needle aspirates of pancreatic cancer with next-generation sequencing.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. e15225-e15225
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. e15225-e15225
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.15_suppl.e15225
    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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