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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. 4141-4141
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 4_suppl ( 2013-02-01), p. 197-197
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 197-197
    Abstract: 197 Background: Due to the small anatomic size, multiplicity of epitheliums, and suboptimal diagnostics determining the site of origin of periampullary adenocarcinomas (PAA) is a challenge. We investigated the ability of a 92-gene RT-PCR assay (CancerTYPE ID) to categorize PAA and to prognostically stratify ampullary adenocarcinomas. Methods: 45 PAA patients who underwent pancreaticoduodenectomies were included; samples were histopathologically verified for tumor subtype determination (pancreatic, extrahepatic biliary, ampullary, or duodenal). Blinded FFPE tumor sections underwent molecular testing and were compared for concordance to histopathological tumor types and prognostic performance. 28 of these samples had previously undergone whole-genome RNA profiling (Overman et al. GI ASCO 2011 a161). Results: Molecular classification of 43 (96%) evaluable samples (13 ampullary, 10 pancreatic, 10 biliary, 10 duodenal) showed 91% concordance: ampullary [5 intestinal (int), 7 pancreaticobiliary (pb)], pancreatic [10 pb] , duodenal [3 int, 7 gastroesophageal (ge)], biliary [7 pb] . The 92-gene assay was prognostic with a median OS of 70 m for ge/int cases vs. 32 m for pb cases, P=0.05. Discordant classifications were ge for 1 ampullary and 2 biliary samples, and ovary for 1 biliary case. Previous unsupervised RNA hierarchical clustering of all 13 ampullary cases had identified two prognostic groups (a good-prognosis int-like and a poor-prognosis pb-like), which were identical to the 92-gene classification for 12 cases (5 int and 7 pb). These two ampullary subgroups were prognostic with median OS of 63 vs. 24 m, P=0.07, respectively. Conclusions: The 92-gene assay demonstrated diagnostic utility for molecular site-of-origin classification of PAA. These results support exploration of this approach for the management of metastatic PAA (in which pathologic review of a primary resection specimen is not an option). Molecular classification of ampullary adenocarcinomas into intestinal and pancreaticobiliary subgroups is prognostically relevant; these and the gastric-like molecular profile of duodenal adenocarcinomas may have therapeutic implications.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 4133-4133
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 4133-4133
    Abstract: 4133 Background: Due to the small anatomic size, multiplicity of epitheliums, and suboptimal diagnostics determining the site of origin of PAA is a challenge. We investigated the ability of a 92-gene RT-PCR assay (CancerTYPE ID) to categorize PAA and to prognostically stratify ampullary adenocarcinomas. Methods: 171 PAA patients who underwent pancreaticoduodenectomies were included; samples were histopathologically verified for tumor subtype determination: pancreatic (PAN), extrahepatic biliary (EB), ampullary (AMP), or duodenal (DOUD). Blinded FFPE tumor sections underwent molecular testing. Analytical sets were an initial 45 PAA set evaluating concordance to histopathological tumor types and prognostic performance, and a second set of 126 AMP and DOUD adenocarcinoma for validation of prognostic performance. Results: Of the initial 45 patient cohort, molecular classification of 43 (96%) evaluable samples (13 AMP, 10 PAN, 10 EB, 10 DOUD) showed 91% concordance: AMP [5 intestinal (int), 7 pancreaticobiliary (pb)], PAN [10 pb] , DOUD [3 int, 7 gastroesophageal (ge)], EB [7 pb] . The 92-gene assay was prognostic with a median OS of 70 m for ge/int cases vs. 32 m for pb cases, P=0.05. Discordant classifications were ge for 1 AMP and 2 EB samples, and ovary for 1 EB case. Previous unsupervised RNA hierarchical clustering (Overman GI ASCO 2011 a161) of all 13 AMP cases had identified two prognostic groups (a good-prognosis int-like and a poor-prognosis pb-like), which were identical to the 92-gene classification for 12 of the 13 cases. Conclusions: In the initial cohort of 45 patients, the 92-gene assay demonstrated diagnostic utility for molecular site-of-origin classification of PAA; evaluation of the remaining 126 ampullary and duodenal cases will be presented. Results support exploration of this approach for the management of metastatic PAA (in which pathologic review of a primary resection specimen is not an option). Molecular classification of ampullary adenocarcinomas into intestinal and pancreaticobiliary subgroups is prognostically relevant; these and the gastric-like molecular profile of duodenal adenocarcinomas may have therapeutic implications.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: JAMA Surgery, American Medical Association (AMA), Vol. 152, No. 11 ( 2017-11-01), p. 1048-
    Type of Medium: Online Resource
    ISSN: 2168-6254
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2017
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e15799-e15799
    Abstract: e15799 Background: Given the benefit noted with epidermal growth factor receptor (EGFR) antibodies in KRAS wild-type colorectal cancer, we conducted a phase II trial to evaluate the efficacy of panitumumab in metastatic small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Methods: This is a single-center open-label single arm two-stage phase II study. The primary objective was response rate (RR). Secondary objectives included overall progression-free survival (PFS), overall survival (OS) and toxicity. Eligibility included: KRAS exon 2 wild-type, ECOG PS 0-1, metastatic disease, adequate organ function and prior progression or intolerance to fluoropyrimidine with oxaliplatin. Panitumumab was administered at a dose of 6mg/kg IV every 14 days. Next generation sequencing panels were used for genomic analysis. Results: 9 patients [M/F 7/2, median age: 61 yrs (range: 40-74), ECOG PS 0/1: 2/7] were enrolled from September 2013 to October 2015. 1 pt had AAC (pancreaticobiliary subtype) and 8 pts had SBA (duodenal in 3, jejunal/ileal in 5). The most common toxicity was grade 1 acneiform rash in all patients. The most common grade 2/3 toxicities were anemia (33%), fatigue (22%), hypomagnesemia (22%) and skin infection (22%). None of the patients had a response, 2 patients had SD while the remaining 7 patients had PD. At a median follow-up time of 16.6 months, the median PFS and median OS were 2.4 months and 5.6 months, respectively. Extended RAS mutational testing identified 0/9 patients with mutations in extended KRAS or NRAS. Further genomic analysis of genes relevant to anti-EGFR activity (BRAF, PIK3CA and ERBB2) identified 2/9 patients with BRAF G469A mutation, 1/9 patients with PIK3CA H1047R mutation, and 0/9 patients with ERRB2 mutations. Conclusions: Although well tolerated, panitumumab had minimal clinical activity in patients with metastatic SBA and AAC. Given recent findings suggesting that right-sided colon cancers (hindgut derivation) benefit less from anti-EGFR therapy compared to left-sided colon cancers (midgut derivation), we propose that our findings may relate to the primarily foregut (proximal duodenum) and midgut (distal duodenum to ileum) derivation of the small bowel. Clinical trial information: NCT01202409.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Pancreatology, Elsevier BV, Vol. 20, No. 3 ( 2020-04), p. 501-504
    Type of Medium: Online Resource
    ISSN: 1424-3903
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2043694-4
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  • 7
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 580-580
    Abstract: Background Risk of VTE is high in cancer patients, especially, in patients with APC. Treatment with chemotherapy further increases the risk. Purpose of the study was to evaluate the safety and efficacy of primary thromboprophylaxis with dalteparin in reducing the incidence of VTE in APC patients planned to start chemotherapy; and to determine the baseline risk factors/biomarkers predictive of VTE. Methods Patients with metastatic or locally advanced pancreatic cancer planned to start chemotherapy were randomized 1:1 to dalteparin vs control arms, stratified for the presence of metastasis and central venous catheter (CVC). The treatment arm received dalteparin 5000 U SQ daily for 16 weeks during chemotherapy and the control arm received chemotherapy alone. Bilateral compression ultrasound of the lower extremities was performed at baseline, and during study (weeks-8 and-16). In addition, blood was collected to identify biomarkers such as, plasma D-dimer levels, platelet activation markers (P-selectin), thrombin-antithrombin complex (TAT), prothrombin fragments 1 and 2 (F1+2), and cytokine levels. Univariate and multivariate logistic regression analysis of clinical and laboratory parameters were done to identify risk factors associated with the development of VTE. Results Of 87 patients enrolled, 75 were randomized to dalteparin (38 patients) or control (37 patients) arms; 8 did not meet the eligibility criteria (including 6 found positive for incidental VTE on screening ultrasound), and 4 withdrew consents before randomization. There were 41 males and 34 females; with median age 52 (range, 36-77 years). Over half of the patients (55% dalteparin arm and 54% control arm) completed 16 weeks on study. All 75 patients were evaluable for response in an intent-to-treat analysis. During the study, the incidence of VTE was 22% [8/37 patients; 2 pulmonary emboli (PE) and 6 deep vein thrombosis (DVT)] on the control arm as compared to 5% (2/38 patients; both DVT) on the dalteparin arm (p = 0.02). In the multivariate analysis, baseline plasma levels of D-dimer, ECOG performance status, presence of CVC, and prophylaxis with dalteparin were independent factors predictive of risk for VTE, as shown below. There was no statistically significant difference in overall survival between the two arms; however, there were higher proportion of patients with elevated baseline D-dimer levels in the dalteparin arm than the control arm (≥ 5000 ng/mL 16% vs 3%). Elevated baseline D-dimer level (≥ 5000 ng/mL) was also predictive of the presence of silent or asymptomatic VTE at screening for study entry (p=0.001), suggesting its potential value in identifying patients with silent VTE. Treatment with dalteparin was well tolerated; the main adverse events included minimal bruising (5/34, 15%), or pain (2/34, 6%) at the injection sites. There were no clinically significant bleeding episodes in the dalteparin arm. Conclusions The results of this study showed that the incidence of VTE is very high in patients with APC. Primary thromboprophylaxis with dalteparin was well tolerated and was associated with 75% reduction in the incidence of VTE in ambulatory patients with locally advanced or metastatic cancer while receiving chemotherapy. Baseline risk factors such as elevated D-dimer levels may help identify high risk patients for primary thromboprophylaxis as well as patients with the presence of asymptomatic VTE. Disclosures: Vadhan-Raj: Eisai: Research Funding. Off Label Use: Fragmin (Dalteparin): Prophylaxis of VTE in ambulatory cancer patients while receiving chemotherapy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 8
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2019
    In:  The Oncologist Vol. 24, No. 6 ( 2019-06-01), p. e384-e386
    In: The Oncologist, Oxford University Press (OUP), Vol. 24, No. 6 ( 2019-06-01), p. e384-e386
    Abstract: Currently, treatment of small bowel adenocarcinoma (SBA) mirrors that of colorectal cancer (CRC). Recent genomic data have demonstrated SBA to be a genetically unique entity, suggesting that therapies not traditionally utilized in CRC should be explored. In order to further characterize the activity of taxanes in this rare cancer, we completed a single-center retrospective study. Twenty patients were found to have been treated with taxane-based regimens (monotherapy in 3, combination therapy in 17). Median time to progression was 3.8 months (95% confidence interval [CI] 2.9–4.6), and median overall survival was 10.7 months (95% CI: 3.1–18.3). The results of this study demonstrate clinical activity from taxane-based therapy in advanced SBA and support further clinical trial investigation.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2023829-0
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  • 9
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 24_Supplement ( 2019-12-15), p. B36-B36
    Abstract: Background: More than half of patients (pts) with pancreatic cancer (PC) initially present with unresectable, locally advanced disease (LAPC). Data on management of these pts after systemic chemotherapy are scarce. Many clinicians utilize a strategy of induction chemotherapy followed by consolidative concurrent chemoradiation (CRT) for pts not progressing on initial chemotherapy. How to manage pts after CRT is controversial. We sought to evaluate the role of maintenance chemotherapy (MCT) after CRT in pts with LAPC. Methods: We retrospectively analyzed LAPC pts treated with CRT at MD Anderson from 2005-2018. Pts who were taken for curative-intent surgery were excluded. Primary and secondary outcomes were median progression-free survival (mPFS) and median overall survival (mOS), respectively, as measured from the start date of CRT. Data were also obtained on pt demographics, response, and duration of induction chemotherapy as well as MCT regimens. Results: We included 165 pts with LAPC treated with CRT in our analysis. Median age was 66 (range 39 – 84), and 97 (59%) pts were male. Median follow-up was 12.9 months. The median duration from initiation of induction chemotherapy to start of CRT was 4.4 months. Most pts (84%) received 1 line of induction chemotherapy prior to CRT. Ten pts (6%) did not receive induction chemotherapy and 17 pts (10%) received at least 2 lines prior to CRT. All but 9 pts (94%) developed disease progression (PD) after CRT, and 49 pts (33%) had PD within 3 months of CRT. On univariate analysis, PD on the induction chemotherapy regimen immediately prior to CRT was associated with shortened PFS (HR 2.46, p & lt; 0.001) and OS (HR 2.96, p & lt; 0.001) after CRT. Most pts (78%) did not receive MCT after CRT. 69% of pts who received MCT were male, compared to 56% of those who did not receive MCT. The percentages of pts who had PD on the chemotherapy regimen immediately prior to CRT in the MCT and no-MCT groups were 9% and 12%, respectively. Sixteen pts who received MCT were treated with either gemcitabine alone or a gemcitabine-containing regimen, while 14 pts received capecitabine monotherapy. On univariate analysis, the use of MCT after CRT was associated with prolonged mPFS (9.0 vs. 4.2 months, p = 0.01), but was not associated with an increase in mOS (15.5 vs. 12.5 months, p = 0.14). On multivariable analysis controlling for race, radiation dose, age, and whether there was progression on the chemotherapy regimen prior to CRT, the use of MCT was significantly associated with both prolonged PFS (HR 0.45, p & lt; 0.001) and OS (HR 0.66, p = 0.047). Conclusions: In this single-institution retrospective analysis of 165 pts with LAPC treated with CRT, treatment with post-CRT MCT was associated with a significant improvement in both PFS and OS as measured from the start date of CRT. Based on these results, MCT may be an appropriate option for pts with LAPC who have not progressed following consolidative CRT, and a prospective trial should be performed to better address this knowledge gap. Citation Format: Jonathan D. Mizrahi, Shalini Moningi, Graciela M. Nogueras-Gonzalez, Robert A. Wolff, Milind M. Javle, Gauri R. Varadhachary, Linus Ho, David R. Fogelman, Kanwal P. Raghav, Michael J. Overman, Christopher H. Crane, Joseph M. Herman, Albert C. Koong, Eugene J. Koay, Jane E. Rogers, Shubham Pant. Maintenance chemotherapy after chemoradiation in patients with locally advanced pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B36.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 10
    In: Human Pathology, Elsevier BV, Vol. 46, No. 9 ( 2015-09), p. 1315-1322
    Type of Medium: Online Resource
    ISSN: 0046-8177
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 2041481-X
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