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  • American Society of Clinical Oncology (ASCO)  (44)
  • 2010-2014  (44)
  • 1
    Online Resource
    Online Resource
    A phase 2, open-label study of rucaparib in patients with pancreatic cancer and a known deleterious BRCA mutation.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. TPS4161-TPS4161
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. TPS4161-TPS4161
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.15_suppl.tps4161
    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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  • 2
    Online Resource
    Online Resource
    Outcomes of patients with advanced cancer and KRAS mutation in phase I clinical trials.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e22086-e22086
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e22086-e22086
    Abstract: e22086 Background: The prognostic significance of KRAS mutations varies by mutation type. We compared the outcomes of patients with different KRASmutations treated in phase I clinical trials. Methods: Patients with advanced cancer and KRAS mutation who were treated in the phase I program from 9/08 to 12/12 were analyzed. The presence and type of KRAS mutation in the patients’ tumor samples were assessed in a CLIA-certified laboratory using PCR, sequenom analysis or next-generation sequencing. We compared clinical outcomes according to type of mutation, tumor, and therapy. Results: KRAS mutations were identified in 365 patients (codon 12, n=278; codon 13, n = 49; other codon, n = 38). The median age was 59 yrs (range, 18-87); and 46% men. Of 365 patients, 260 had KRAS mutation alone; 105 patients had 130 additional aberrations: PI3KCA, n=45 (39%); p53, n=29 (25.2%); PTEN, n=22 (19%); other, n=34 (29%). Of 260 patients, 159 were treated and evaluable for response. Outcomes in patients with KRAS mutation alone or with KRAS and additional molecular aberrations are shown in the Table. Conclusions: Keeping in mind that the number of patients was small, our results demonstrate heterogeneity in outcomes of patients with KRAS mutations. Combination studies of MEK inhibitors with other drugs may have improved antitumor activity. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.e22086
    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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  • 3
    Online Resource
    Online Resource
    Molecular classification of ampullary adenocarcinoma: Comparative prognostic performance of the 92-gene assay versus histomolecular analysis.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. 4141-4141
    Details
    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
    URL: Article
    DOI: 10.1200/jco.2014.32.15_suppl.4141
    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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  • 4
    Online Resource
    Online Resource
    Impact of multidisciplinary therapy on high-grade appendiceal adenocarcinoma (AA).
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 4134-4134
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 4134-4134
    Abstract: 4134 Background: AA is a rare malignancy ranging from well-differentiated to poorly differentiated carcinoma, including those with signet ring cells. Optimal therapy for low grade peritoneal disease is cytoreductive surgery (CRS) combined with heated intraperitoneal chemotherapy (HIPEC). However, some patients (pts) are suboptimal for CRS/HIPEC, and are considered for systemic chemotherapy (SC) alone, or SC + CRS. In light of our previously reported overall survival (OS) benefits for the role of SC in metastatic AA, here we explore the impact of surgical intervention on OS in these pts. Our aim was to clarify the OS benefit of multidisciplinary therapy (SC + CRS + HIPEC) in those pts with aggressive tumor biology. Methods: A retrospective chart review of AA pts registered in our tumor registry between Jan. 2005 to Dec. 2009 was undertaken to identify patients with AA who received SC. Electronic medical records (EMR) were reviewed for CRS, HIPEC, histology, SC, and OS. The K-M method and Log-Rank test were used for statistical analysis. Results: Of 143 AA pts, 52 (36%) pts were high grade with 33 (23%) having signet ring cells. After a median follow-up of 35M, high grade tumors were noted to have worse OS overall (24M vs 56M, p 〈 .001). When comparing treatment received, and adjusting for tumor biology, those pts with high grade disease again fared worse, and experienced comparatively worse OS. However, those treated with SC + CRS + HIPEC experienced the longest median survival. Conclusions: Pts with peritoneal disease from high grade AA who completed SC with CRS + HIPEC experienced prolonged OS compared to those treated by SC +/- CRS. Our data suggest that SC + palliative CRS offers minimal benefit for high grade disease. Selection bias influences these results heavily; as those who do well proceed to complete all components of therapy. A treatment plan that includes SC + CRS + HIPEC can result in durable survival, and is a strategy that warrants further study emphasizing the importance of multidisciplinary management. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.4134
    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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  • 5
    Online Resource
    Online Resource
    Choice of chemotherapy in the treatment of metastatic squamous cell carcinoma of the anal canal.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 4060-4060
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 4060-4060
    Abstract: 4060 Background: Metastatic squamous cell carcinoma (SCCA) of the anal canal is an uncommon malignancy with no standard approach. The reported median overall survival (OS) is 9-12 months (M) following 5-FU + cisplatin (FC)-based therapy. The aim of this study is to evaluate first-line chemotherapy approaches in this patient (pt) population. Methods: A retrospective analysis was conducted of 428 pts with metastatic SCCA of the anal canal identified from the MDACC tumor registry between 1/1/2000 - 5/31/2011. Electronic medical records were reviewed for histology, date of diagnosis and/or recurrence, site of metastasis, type of therapy provided, response rate (RR), progression-free survival (PFS), OS, and lines of salvage therapy. All eligible pts were required to be treatment-naïve for metastatic disease and have radiographic imaging at MDACC. Waiver of informed consent was obtained. Results: 99 pts fulfilled all criteria; 10 were lost to follow-up; 12 did not initiate chemotherapy. 77 pts were evaluable; M: F = 20:57; median age = 55 years (range: 37 - 82); HIV(+) = 5% (4/77); prior chemoXRT with curative intent: 70% (54/77), complete response (CR): 87% (47/54), median time to development of metastatic disease =17M. 29% (22/77) presented with metastatic disease. Sites of disease included distant lymph nodes (41%); liver (45 %); lung (25%); bone (15%); and brain (8%). The median follow up was 37M. 73% (56/77) of patients were treated with platinum-based therapy; 51% (n=39) received FC and 22% (n= 17) received carboplatin + paclitaxel (CP). The median PFS was 6M; FC trended better than CP for PFS (7M vs. 5M, p 〈 0.067). The overall median OS = 29M. 40% (31/77) of pts received neoadjuvant first-line therapy followed by metastasectomy (68%), XRT (26%), or both (6%); resulting in a median OS = 35M. Conclusions: Metastatic SCCA of the anal canal is a malignancy in which 5-FU+cisplatin is a commonly used regimen. Our analysis suggests FC results in improved PFS over CP but is underpowered supporting further analysis. The short median PFS with front-line chemotherapy, and yet longer OS reflects the challenges in treating this patient population and the importance of multidisciplinary management in select cases.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.4060
    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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  • 6
    Online Resource
    Online Resource
    Association of human papillomavirus with unique clinicopathologic features in patients with metastatic squamous cell carcinoma of the anal canal.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 3_suppl ( 2014-01-20), p. 479-479
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 479-479
    Abstract: 479 Background: The incidence of anal carcinoma in the United States continues to increase steadily, and infection with the human papillomavirus (HPV) is an established risk factor for the development of anal carcinoma. However, clinicopathologic characteristics of patients with metastatic squamous cell carcinoma of the anal canal according to HPV status have thus far not been defined. Methods: Records of patients treated for metastatic squamous cell carcinoma of the anal canal at the MD Anderson Cancer Center between June 2005 and August 2013 were reviewed. Patients were tested for the presence of HPV DNA by in-situ hybridization and/or the p16 oncoprotein by immunohistochemistry. Associations between the presence of HPV and clinicopathologic attributes were measured by calculation of odds ratios, and survival was estimated according to the Kaplan-Meier method. Results: Patients were followed for a mean of 50.2 months, and the mean age at diagnosis was 54.0 years. Among the 43 patient records reviewed, 39 tumors (90.1%) tested positive for the presence of HPV. Patients with HPV-negative tumors were more likely to have a strong ( 〉 30 pack-year) tobacco history (OR=18.5, p=0.018) and were more likely to develop brain metastases (OR=2.0, p=0.04). A faint association was observed between Caucasian ethnicity and HPV-positive tumors (OR=8.8, p=0.06). Median survival from the time of diagnosis of metastatic disease was 42.4 months, with a trend towards a worse survival seen among patients with HPV-negative tumors (HR for death 4.9, p=0.09). Conclusions: Differences in HPV status and prior tobacco exposure may identify two separate populations of patients with metastatic squamous cell anal carcinoma with different clinicopathologic phenotypes. Our results are similar to prior published data in patients with squamous cell carcinoma of the head and neck in which patients with HPV-positive tumors demonstrate improved survival outcomes. Data from additional patients will be presented.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.3_suppl.479
    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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  • 7
    Online Resource
    Online Resource
    Phase II Trial of Cetuximab, Gemcitabine, and Oxaliplatin Followed by Chemoradiation With Cetuximab for Locally Advanced (T4) Pancreatic Adenocarcinoma: Correlation of Smad4(Dpc4) Immunostaining With Pattern of Disease Progression
    American Society of Clinical Oncology (ASCO) ; 2011
    In:  Journal of Clinical Oncology Vol. 29, No. 22 ( 2011-08-01), p. 3037-3043
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 22 ( 2011-08-01), p. 3037-3043
    Abstract: This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC). Patients and Methods Treatment-naive eligible patients (n = 69) received intravenous gemcitabine (1,000 mg/m 2 ) and oxaliplatin (100 mg/m 2 ) every 2 weeks for four doses, followed by radiation (50.4 Gy to the gross tumor only) with concurrent capecitabine (825 mg/m 2 twice daily on radiation treatment days). Cetuximab (500 mg/m 2 ) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy. Diagnostic cytology specimens were immunostained for Smad4(Dpc4) expression. Results Median overall survival time was 19.2 months (95% CI, 14.2 to 24.2 months), and 1-year, 2-year, and 4-year actuarial overall survival rates were 66.0%, 25.02%, and 11.3%, respectively. Acneiform rash correlated with improved survival (P = .001), but initial CA19-9, borderline resectable initial stage, and surgical resection (n = 7) did not. The 1-year and 2-year radiographic local progression rates were 22.8% and 61.0%, respectively. The worst acute toxic effects were GI toxicity (32% and 10% for grades 2 and 3, respectively); fatigue (26% and 6% for grades 2 and 3, respectively); sensory neuropathy (9% and 1% for grades 2 and 3, respectively); and acneiform rash (54% and 3% for grades 2 and 3, respectively). Smad4(Dpc4) expression correlated with a local rather than a distant dominant pattern of disease progression (P = .016). Conclusion This regimen appears effective and has acceptable toxicity. The primary end point (1-year overall survival rate 〉 45%) was met, with encouraging survival duration. Smad4(Dpc4) immunostaining correlated with the pattern of disease progression. Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized pancreatic cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2010.33.8038
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2011
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    Diagnostic utility and prognostic performance of a 92-gene cancer classifier to molecularly profile periampullary adenocarcinomas (PAA).
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 4133-4133
    Details
    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
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.4133
    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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  • 9
    Online Resource
    Online Resource
    Diagnostic utility and prognostic performance of a 92-gene cancer classifier to molecularly profile periampullary adenocarcinomas.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 4_suppl ( 2013-02-01), p. 197-197
    Details
    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
    URL: Article
    DOI: 10.1200/jco.2013.31.4_suppl.197
    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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  • 10
    Online Resource
    Online Resource
    Characteristics and survival of patients with advanced cancer and TP53 mutations in phase I clinical trials.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 2545-2545
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 2545-2545
    Abstract: 2545 Background: The classical hot spot mutations within the central sequence-specific DNA-binding region of p53 protein (R175H in exon 5 and G245S, R248Q, R249S, R273H and R282W in exon 8) disrupt its ability to bind to DNA. These inactivating point mutations of p53 may result in loss of its function and/or acquisition of a gain of function, which has been associated with the development of invasive and metastatic tumors in mouse models. We assessed the frequency and survival of p53 mutations in patients with advanced cancer. Methods: P53 mutation in patients’ tumor was identified in a CLIA-certified laboratory using PCR, sequenom analysis or next generation sequencing. Results: P53 mutations were identified in 212 patients. Median survival by tumor type and distribution of p53 mutations by exon are shown in the Table. The median survival (from time of referral to Phase I clinic) by mutations in “hot spot” amino acids was as follows: R175H, 9.1 months (n=18); R248Q, not reached/5 deaths (n=22); R273H, 12.6 months (n=11); other mutations, 11.9 months (n=160). The median survival of patients with a tumor mutation in exons 5 or 8 appeared to be shorter than that of patients with mutations in other exons (9.4 vs. 14.6 months) although the difference was not statistically significant (p=.12) owing to the small number of patients. Conclusions: Our results demonstrate that the distribution and clinical significance of various p53 mutations differs by tumor type and suggest that mutations in R248Q may be associated with longer survival. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.2545
    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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