tbuckley/cabot-search huggingface dataset:
Clinical activity of abiraterone acetate in patients with castration-resistant prostate cancer who received prior ketoconazole therapy.
Authors: Bo Zhao, Jorge A. Garcia, Timothy D. Gilligan, Brian I. Rini, Robert Dreicer
Journal: Journal of Clinical Oncology (2014)

99 Background: Studies have shown activity of Abiraterone acetate (AA) in patients (pts) with castration-resistant prostate cancer (CRPC) who have received prior ketoconazole. Prostate-specific antigen (PSA) response to AA in relation to previous PSA response to ketoconazole was investigated. Methods: A retrospective analysis was conducted to determine the clinical activity of AA in men with CRPC who have received prior ketoconazole therapy at our institution. Time to PSA progression (PSA TTP) was defined by PCWG2 criteria, a PSA reduction of 50% or more was considered as PSA response. Results: Thirty four pts were identified. Nineteen pts (56%) had previous PSA responses on ketoconazole, with a median PSA TTP of 11 months (95% confidence interval [CI] 6.8-19.9). Subsequently, 11 of 34 (33%) of pts achieved a PSA response on AA, with a median PSA TTP of 6 months (95% CI 4.9-9.5). Among the 19 pts having a PSA response on ketoconazole, only four (21%) pts subsequently had PSA response to AA. Two of these pts had transient PSA response with PSA TTP less than 3 months on kKetoconazole, one patient discontinued Ketoconazole due to side effects, one patient had intermittent non-castrate testosterone levels. In contrast, 7 of 15 (46.7%) pts without prior PSA response to ketoconazole subsequently achieved PSA response on AA (p=0.11). Of note, PSA reduction of less than 50% on AA was observed in 9 of 34 pts (26%), which was associated with a longer median PSA TTP compared to pts who had PSA-progressive disease (5.9 months [95% CI 3.5-7.3] vs.1.5 months [95% CI 1.0-3.5], p=0.028). Five of these nine patients had a prior PSA response to ketoconazole but required drug discontinuation for reasons other than disease progression. Conclusions: PSA response to prior ketoconazole therapy is associated with lower PSA response rate to subsequent AA. The observation suggests that there is a biologically distinct subset of patients who are ketoconazole-resistant but abiraterone-sensitive, the underlying mechanism needs to be further investigated.
Impact of care at NCI comprehensive cancer centers (NCICCC) on cancer outcome: Results from a population-based study.
Authors: Julie Anna Wolfson, Can-Lan Sun, Tongjun Kang, Laura Wyatt, Arti Hurria, Smita Bhatia
Journal: Journal of Clinical Oncology (2014)

6541 Background: Despite advances in therapy and supportive care, prognosis for certain cancers remains poor. Rigorous processes ensure quality of research, clinical care and education at NCICCC. However, impact of site of care on survival and access to NCICCC for vulnerable subpopulations (race/ethnicity, payor) remains unstudied. Methods: We constructed a population-based cohort of 53,618 patients diagnosed between 22y - 65y with adult-onset cancers and reported to LA County cancer registry between 1998 - 2008. Geographic Information Systems (ArcGIS) was used for geospatial analysis. Results: Across multiple diagnoses, patients at NCICCC showed superior 5y overall survival (OS) as compared to those at community sites (breast [n=31,770]: 89% vs. 86%, p<0.01; lung [n=10,855]: 28% vs. 17%, p<0.01; hepatobiliary [n=4,296]: 34% vs. 19%, p<0.01; gastric [n=2,678] 32% vs. 22%, p<0.01; pancreas [n=2,326]: 13% vs. 6%, p<0.01; oral [n=1,838]: 68% vs. 59%, p=0.01). Adjusting for clinical (age, stage, gender) and sociodemographic (race/ ethnicity, payor, socioeconomic status [SES]) characteristics, multivariable Cox regression revealed an increased risk of mortality in patients receiving care at non-NCICCC sites: Breast: hazard ratio (HR)=1.2, p<0.01; Lung: HR=1.5, p<0.01; Hepatobiliary: HR=1.4, p<0.01; Gastric: HR=1.4, p<0.01; Pancreas (n=2,326), HR=1.5, p<0.01; Oral: HR=1.3, p=0.05. Overall 7% of patients were seen at NCICCC (range 4-16%, p<0.01). Multivariable logistic regression adjusting for clinical characteristics revealed that low SES (OR range across diagnoses: 0.4-0.5, p<0.01), public (OR 0.4-0.9, p<0.03) or no (OR 0.1-0.7, p<0.04) insurance, African-American race (OR 0.4-0.6, p<0.03) or Hispanic ethnicity (OR 0.5-0.7, p<0.02), and residing > 9 miles from nearest NCICCC (OR 0.5-0.9, p<0.01) decreased likelihood of care at NCICCC. Conclusions: Population-based data reveal superior OS among adult-onset cancer patients receiving care at NCICCC. Patients without private insurance, from low SES, African-American and Hispanic backgrounds or living more than 9 miles from an NCICCC, are less likely to use NCICCC. Barriers to care at NCICCC are currently being explored.
Phase II trial of erlotinib plus sirolimus for recurrent glioblastoma multiforme (GBM)
Authors: H. S. Friedman, A. Desjardins, J. J. Vredenburgh, J. N. Rich, S. Sathornsumetee, S. Gururangan, J. A. Quinn, D. A. Reardon
Journal: Journal of Clinical Oncology (2008)

2062 Background: Erlotinib, an EGF receptor kinase inhibitor, has limited single-agent activity in recurrent GBM patients. The antiglioma activity of EGFR inhibitors is enhanced by inhibitors of the mammalian target of rapamycin (mTOR), such as sirolimus, in preclinical studies. Methods: This phase II study assesses the antitumor activity of erlotinib plus sirolimus among recurrent GBM patients. Eligibility criteria: histologically confirmed GBM; age ≥18 years; KPS ≥ 70%; adequate hepatic, renal, and bone marrow function and lack of prior EGFR or mTOR-directed therapy. Patients not on enzyme-inducing anticonvulsants (EIAC; phenytoin, carbamazepine, oxcarbazepine and phenobarbitol) receive 150 mg of erlotinib and 5 mg of sirolimus per day, while those on EIAC receive 500 mg of erlotinib and 10 mg of sirolimus per day. Patients are evaluated after every other 28-day cycle. The primary endpoint is 6-month progression-free survival. Results: To date 27 patients have enrolled with a median age of 53.2 years (range 39.9–69.1) and a median of 2 prior episodes of progressive disease (range, 1–3). Only 26% are on EIAC. Toxicities appear comparable for patients on and not on EIAC and most commonly include rash (grade 3, 8%; grade 2, 30%), nausea/emesis (grade 3, 4%; grade 2, 15%), mucositis (grade 2, 19%, grade 3, 4%), diarrhea (grade 2, 4%; grade 3, 7%) and hyperlipidemia (grade 2, 7%). There have been no grade 4 or 5 attributable events. Three patients discontinued therapy due to toxicities including persistent grade 2 thrombocytopenia (n=1) and grade 2 diarrhea/rash (n=2). Best responses to date include stable disease (n=9, 33%) and progressive disease (n=13, 48%). Four patients (15%) are too early and one patient is lost to follow-up. Four patients with stable disease continue on study therapy after 6, 2 (n=2) and 1 cycle, respectively. Conclusions: Combination of erlotinib and sirolimus has modest toxicity and antitumor activity among unselected patients with recurrent GBM. Further accrual, treatment and follow-up are ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology, Schering-Plough Genentech Genentech™ BioOncology, Schering-Plough
Survival outcome of metastatic adenocarcinoma of esophagogastric junction in the trastuzumab era.
Authors: Yukiya Narita, Hiroko Hasegawa, Azusa Komori, Seiichiro Mitani, Toshiki Masuishi, Hiroya Taniguchi, Shigenori Kadowaki, Takashi Ura, Masashi Ando, Seiji Ito, Yasushi Yatabe, Masahiro Tajika, Kei Muro
Journal: Journal of Clinical Oncology (2016)

117 Background: Previous studies have reported no differences in treatment outcomes between metastatic adenocarcinoma esophagogastric junction (AEGJ) and gastric adenocarcinoma (GAC). However, after the approval of trastuzumab (Tmab) for the treatment of metastatic AEGJ and GAC survival outcomes remain unclear. Methods: We retrospectively reviewed clinicopathological characteristics, treatment outcomes, and prognoses of 289 consecutive patients with AEGJ and GAC who received ﬁrst-line chemotherapy from March 2011, when Tmab was approved in Japan, to December 2013 at Aichi Cancer Center Hospital. Prognostic factors were identified using Cox multivariate regression analysis. IHC3+ or IHC2+/ISH+ tumors were defined as HER2 positive. Results: Of 289 patients, 45 (16%) had AEGJ. Patients with AEGJ were signiﬁcantly younger with lesser lung metastases than those with GAC. HER2-positive rates in AEGJ tended to be greater than those in GAC, but this difference was not statistically significant (22% vs. 16%; P = 0.35). The rates of platinum doublet therapies were not significantly different (72% vs. 78%; P = 0.47). The objective response rate (ORR) was 27% with AEGJ and 40% with GAC (P = 0.17). The median follow-up duration was 12.1 and 11.9 months, respectively. Progression-free survival was similar for both the groups [hazard ration (HR) = 0.97; P = 0.83), while the median overall survival (OS) period was numerically longer for AEGJ than that for GC (14.7 vs. 12.4 months; HR = 0.99; 95% confidence interval = 0.69–1.39; P = 0.92). In patients with AEGJ, an ECOG performance status of 2 and HER2 negativity were signiﬁcantly associated with poor prognosis, as estimated by the multivariate analyses of OS. The analyses that were limited to patients treated with Tmab as the first-line chemotherapy revealed no significant differences in ORR and median OS between AEGJ and GAC. Conclusions: Even in the Tmab era, there were no significant differences in survival outcomes between metastatic EGC and GAC.
Reasons for and outcomes of adjuvant chemotherapy choices in elderly patients with resected stage III colon cancer.
Authors: Jenny Ko, Hagen F. Kennecke, Howard John Lim, Sharlene Gill, Ryan Woods, Caroline Speers, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2012)

571 Background: Research suggests that elderly cancer patients are commonly undertreated, but the precise reasons for this are unclear. Robust clinical data on the optimal adjuvant chemotherapy regimen for elderly colon cancer patients are also lacking. Our aims were to: 1) evaluate the impact of advanced age on choice of adjuvant chemotherapy (none vs. capecitabine vs. FOLFOX) for curatively resected colon cancer; b) determine the reasons for selecting a particular regimen; and 3) examine whether treatment effect on outcomes is modified by age. Methods: All patients diagnosed with stage III colon cancer between 2006 and 2008, and referred to any 1 of 5 regional cancer centers in British Columbia, Canada were identified. Descriptive statistics were used to summarize treatment patterns among young patients (YPs) aged &lt;70 years vs. elderly patients (EPs) aged &gt;/=70 years. Multivariate logistic regression models were constructed to evaluate the association between adjuvant chemotherapy and cancer-specific survival (CSS) in YPs and EPs. Results: In total, 810 patients were identified: 51% were male, 52% YPs and 48% EPs, and 74% received adjuvant chemotherapy. When compared to YPs, EPs had worse ECOG and more comorbidities (both p&lt;0.001). EPs were less likely than YPs to receive adjuvant chemotherapy (57% vs. 91%, p&lt;0.001). Frequent reasons for no treatment included age, comorbidities, and small perceived benefit from adjuvant therapy. Among treated pts, EPs were less likely to receive FOLFOX (32% vs. 74%, p&lt;0.0001) in favor of capecitabine due to patient preference, age, and comorbidities. In multivariate analyses, receipt of either FOLFOX or capecitabine was correlated with improved CSS compared to surgery alone. The effect of adjuvant chemotherapy on CSS was not modified by age (interaction p for capecitabine and age = 0.26; interaction p for FOLFOX and age = 0.40). Conclusions: EPs with stage III colon cancer frequently received either no adjuvant treatment or capecitabine monotherapy due to advanced age and co-morbidities. The treatment effect of adjuvant therapy on CSS is similar among EPs and YPs. Adjuvant chemotherapy should not be withheld from colon cancer patients based on advanced age alone.
Viral Infection After Unrelated Cord Blood Transplantation In Bordeaux: Incidence and Outcomes. A Single Centre Experience with Eurocord.
Authors: Pierre-Yves Dumas, Reza Tabrizi, Stephane Vigouroux, Marie-Edith Lafon, Gerald Marit, Arnaud Pigneux, Thibaut Leguay, Krimo Bouabdallah, Marie-Sarah Dilhuydy, Axelle Lascaux, Anna Schmitt, Alessandro Crotta, Vanderson Rocha, Noel-Jean Milpied
Journal: Blood (2010)
Development and validation of a scoring system using insulin-like growth factor to assess hepatic reserve in hepatocellular carcinoma.
Authors: Ahmed Omar Kaseb, Lianchun Xiao, Jung-Hwan Yoon, Manal Hassan, Jeong-Hoon Lee, Hyo-Suk Lee, Young Kwang Chae, James L. Abbruzzese, Jeffrey Morris
Journal: Journal of Clinical Oncology (2014)

231 Background: The Child-Turcotte-Pugh (CTP) score fails to accurately predict survival in hepatocellular carcinoma (HCC), yet remains the standard tool for assessing the liver reserve and guiding therapeutic decisions. CTP relies partially on subjective clinical grading of encephalopathy and ascites. Since liver production of insulin-like growth factor-1 (IGF-1) is significantly reduced in chronic liver diseases and HCC, we hypothesized that IGF-1 could be a valid surrogate for hepatic reserve to replace the subjective parameters in CTP score. Methods: We tested plasma IGF-1 in the training set (n=310). Recursive partitioning identified three optimal IGF-1 ranges that correlated with survival: &gt;50 ng/mL = 1 point; 26-50 ng/mL = 2 points; and &lt;26 ng/mL = 3 points. We modified the CTP score by replacing ascites and encephalopathy with plasma IGF-1, subjected both scores to log-rank analysis, and quantified the prognostic values with C-statistics to compare the scores’ performance. We prospectively validated the score in 150 patients from MDACC; in addition to 180 patients from Korea. Results: The IGF score significantly predicted OS of all classes (p&lt;0·001). In the training cohort, C-indices for CTP and IGF scores were 0·57 and 0·61, respectively (p=0·003 per the U-statistic). Similarly, C-indices in MDACC validation cohort were 0·56 and 0·63 (p=0·02 per the U-statistic), and in Korean cohort were 0·58 and 0·60 (p=0·03 per the U-statistic). Conclusions: The new IGF score is simple and blood-based, and validated well on multiple independent HCC cohorts. It could identify a subpopulation of patients who may benefit from active therapy because of their preserved hepatic reserve, as distinct from patients for whom therapy can be deferred or avoided.
An analysis of the GST genetic polymorphism in cancer risk in Southeastern Brazil
Authors: C. S. Lima, G. J. Lourenço, S. N. Angelo, H. N. Honma, E. F. Silva, H. Nascimento, C. Cardoso-Filho, M. M. Ortega, A. F. Sagarra, F. F. Costa
Journal: Journal of Clinical Oncology (2008)

22053 Background: Several tumors have been linked to chronic exposure to carcinogens found in food and tobacco smoke. The GSTM1 and GSTT1 genes, involved in inactivation of carcinogens, are homozygous null in 10–60% of health individuals. Cancer and environmental-related diseases have been described as serious health problems in south-eastern Brazil. Therefore, the aim of this study was to evaluate the influence of these genes for cancer risk in individuals from this region of the country. Methods: DNA from 892 cancer patients, 38 acute myeloid leukemia (AML), 125 chronic myeloid leukemia (CML), 79 Hodgkin's lymphoma (HL), 106 multiple myeloma (MM), 100 breast cancer (BC), 102 colorectal cancer (CC), 142 head and neck cancer (HNC), and 200 lung cancer (LC), and 715 age and race-matched controls were analyzed by the multiplex-PCR. Results: Similar frequencies of the GSTM1, GSTT1 and combined null genotypes were seen in CML, HL, MM, BC, CC, HNC, and LC patients and controls. Individuals with the distinct genotypes were under similar risks for diseases. In contrast, the frequency of the GSTM1 (73.6% versus 36.9%, P < 0.001), GSTT1 (34.2% versus 18.1%; P < 0.020) and combined (26.3% versus 5.0%; P < 0.001) null genotypes were higher in AML patients than in controls. Individuals with these genotypes were under a 4.7-fold (CI 95%: 2.1–11.0), 1.4-fold (CI 95%: 1.0–5.2) and 6.6-fold (CI 95%: 2.4–17.9) increased risks for AML when compared to others. An excess of the GSTM1 null was seen in MM patients at stage III when compared to those at stages I+II (32 of 71 versus 5 of 29; P = 0.009) and in HNC patients at stage IV compared to those at stage I to III (43 of 83 versus 11 of 54; P < 0.001). The GSTT1 null was more common in CC diagnosed before 60-aged patients than those diagnosed after 60 (15 of 52 versus 2 of 50; P = 0.001). Conclusion: These results suggest that that the inherited absence of the GST pathway alters substantially the risk for AML, the aggressiveness of MM and HNC and the age of CC in individuals of the south-eastern Brazil. Financial support: FAPESP and CNPq. No significant financial relationships to disclose.
Effect of palliative doctor in medical oncology team on patient outcomes.
Authors: Zhi Zhen Xu, Patricia Neo, Tan Ying Peh, Alethea Yee, Xia Zhu, Grace Meijuan Yang
Journal: Journal of Clinical Oncology (2015)

122 Background: Advanced cancer patients have a high symptom burden and not infrequently have unplanned hospital admissions. In our institution, PM services are provided via a separate consult team rather than an integrated palliative oncology team. Sometimes, PM doctors join the oncology team as integrated members for a few months each as part of their PM fellowship training program. This study aims to explore the effect of this PM doctor. Methods: Patients admitted under the lung and gastrointestinal (GI) oncology teams from June 2013 to June 2014 were studied as this cohort of patients had a higher symptom burden and were more likely to benefit from PM input. The following information for each month was obtained from the computer system: hospital length of stay, formal referrals for a PM consult, 30-day, 60-day and 90-day mortality, and place of death. 2-sample T test was used to compare outcomes when there was a PM doctor in the oncology team for at least half of the month versus when there was not. Results: See table below. The presence of a PM doctor reduced the monthly percentage of formal referrals for PM consults but did not have clinically significant effects on other outcomes. Conclusions: PM doctors were there to learn oncology rather than provide a PM service. However, a reduction of PM referrals suggests that they were still able to meet some of the PM needs of the patients admitted. A new model of PM service provision whereby a PM healthcare professional is integrated within the oncology team warrants further study. [Table: see text]
Effect of eribulin on cell growth and PI3K pathway activity with and without RAD001 in triple-negative and HER2-expressing breast cancer.
Authors: David Luyimbazi, Thehang H. Luu, Quanhua Xing, Jin Yan, Dylan Tully, Ernest Soyoung Han, Richard Yip, John H. Yim
Journal: Journal of Clinical Oncology (2013)

173 Background: Patients with triple-negative breast cancer have high levels of Akt expression and activation of the PI3K-mTOR pathway. Eribulin is a microtubule-targeting agent with benefits in treating refractory triple negative disease. Our objective was to evaluate its efficacy in inhibiting PI3K pathway activity and cell growth both alone and in combination with the mTOR inhibitor RAD001. Methods: MDA468, BT549 and SKBR3 breast cancer cell lines were used for this study. MTT assays were used to assess growth inhibition after 72 hour treatment with eribulin alone and in combination with RAD001. Combination indices (CI) generated by Chou-Talalay plots were used to quantify synergy. Western blots were used to evaluate the expression of phosphorylated Akt-Ser473 (pAkt) and S6K1 after 24 hours of treatment with both agents. Results: Both MDA468 and SKBR3 cells treated with eribulin in varying concentrations showed inhibition of pAkt expression. Standard dilutions of eribulin in combination with log dilutions of RAD001 resulted in marked synergistic growth inhibition (CI&lt;&lt;1) in both MDA468 and BT549 cells. Western blot analysis for MDA468 cells treated with the combination erubulin and RAD001 showed a dose related suppression of pAkt along with complete inhibition of pS6K1, while RAD001 alone increased pAkt. Conclusions: Our study shows dose related inhibition of Akt activation as well as inhibition of cell growth in triple negative breast cancer and HER2 cell lines treated with eribulin alone or combined with RAD001. We also show reversal of the pAkt feedback response seen with mTOR inactivation, and a significant synergistic growth inhibition with combination treatment. These findings point to a potential role for eribulin and RAD001 in the treatment of refractory triple-negative breast cancer. [Table: see text]
Comment to the Reply of Rettenmaier and Goldstein, to the Letter to the Editor of Karacan et al., concerning the article Dramatically reduced incidence of the vaginal cuff dehiscence in gynecologic patients undergoing endoscopic closure with barbed sutures: A retrospective cohort study IJS 19 (2015) 27–30
Authors: Rudy Leon De Wilde
Journal: International Journal of Surgery (2017)
Expression of the organic cation transporter SLC22A16 can be a feature of human epithelial ovarian cancers with different histological type
Authors: K. Ota, J.-I. Akahira, N. Sato, T. Moriya, M. Unno, T. Abe, K. Ito, N. Yaegashi
Journal: Journal of Clinical Oncology (2005)

5131 Background: SLC22A16 is an organic cation transporter that is expressed on the plasma membrane of living cells and transports adriamycin into the cytoplasm. In this study, we examined SLC22A16 expression and evaluated its clinical significance in epithelial ovarian cancer. Methods: To evaluate the expression of SLC22A16 gene and protein, 12 ovarian cancer cell lines and 116 human tissues, including 94 ovarian cancers, 5 normal ovaries, 12 ovarian adenomas, and 5 borderline tumors were examined using immunohistochemistry, quantitative reverse transcription -PCR, and western blotting. Results: Positive immunoreactivity for SLC22A16 was detected on the plasma membrane of epithelial tumor cells. Positive immunoreactivity occurred in 15 of 94 (16%) ovarian cancer tissues, 2 of 5 (40%) borderline tumors, and 1 of 12 (8.3%) benign adenomas. Normal ovaries were all negative. The positive ovarian cancer tissues included 2 of 38 (5%) serous adenocarcinomas, 1 of 15 (6.7%) endometrioid adenocarcinomas, and 12 of 26 (20.4%) clear cell adenocarcinomas. SLC22A16 mRNA was significantly more expressed in clear cell adenocarcinomas than in tumors of other histological types (P<0.0001). Western blotting found immunoreactive bands corresponding to SLC22A16 in 10 out of 12 ovarian cancer cell lines. Conclusions: Our results suggest that adriamycin and related anthracyclines taken up through SLC22A16 have the potential to be effective treatment for clear cell adenocarcinoma. No significant financial relationships to disclose.