tbuckley/cabot-search huggingface dataset:
Nuclear survivin expression correlates with poor prognosis in cholangiocarcinoma
Authors: M. Kim, D. Tan, C. Levea, J. Yu, B. Kuvshinoff, S. Duttala, J. Gibbs, M. Javle
Journal: Journal of Clinical Oncology (2004)

4092 Background: Survivin is a unique anti apoptotic protein expressed in many human cancers. It is absent in non-proliferating adult tissues. Its expression and prognostic value in biliary tumors is yet to be elucidated. Methods: Twenty-four consecutive surgical cases of cholangiocarcinoma treated from 1996–2002 at Roswell Park Cancer Institute were studied. Immunohistochemistry was performed on paraffin embedded blocks using mouse monoclonal IgG2a antibody to survivin (Santa Cruz Biotechnology). DAKO high pressure antigen retrieval and mouse envision plus detection systems were used to detect survivin expression. Two pathologists (DT, CL) independently examined survivin expression and scored (0, 1+, 2+, 3+), based on presence and intensity of immunoreactivity in nucleus and cytoplasm. Clinical data were obtained in accordance with IRB approved protocol. Results: Median patient (pt) age was 68 (range 40 to 77). Sixteen pts were female, and 8 male. SEER staging was local in 2, regional in 15 and distant in 7 pts. Treatments included chemotherapy (2 pts), surgery (10), combined modality (10) or no therapy (2). Strong cytoplasmic survivin expression (3+) was seen in 6 cases and strong nuclear survivin (3+) in 4. One case had strong co-expression at both locations. There was no statistical correlation between expression of either cytoplasmic or nuclear survivin with sex, SEER staging or tumor grade. Statistically, cytoplasmic survivin expression did not have prognostic significance. However, 4 pts with strong nuclear survivin had a median survival of 11 months, significantly less than those with weak nuclear survivin expression (20 months, p=0.033). Multivariate analysis using the Cox- proportional hazards model identified the following 4 as best predictors of patient mortality: nuclear survivin (P=0.022), presence of metastasis (P=0.025), age (P=0.019), and use of combined modality therapy (P=0.006). Estimated hazard ratios (HR) suggested pts likely to survive longer were weak nuclear survivin expressers (HR = 3.1) and had non- metastatic disease (HR = 1.5). Conclusions: Nuclear survivin expression in cholangiocarcinoma may identify those with a poor prognosis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MGI Eli Lilly; Genentech; MGI Phama Eli Lily; Pfizer; Roche
The influence of a gene expression profile on breast cancer decisions
Authors: L. R. Henry, S. A. Prindiville, S. M. Swain, R. Cordes, P. W. Soballe M.D.
Journal: Journal of Clinical Oncology (2008)

11546 Background: Gene expression profiles (such as Oncotype Dx Recurrence Score [RS]) show promise for informing adjuvant therapy recommendations in patients with ER-positive breast cancer. The effects of the test are still being defined. We studied the impact of this test upon our actual administration of chemotherapy in patients with ER-positive, node negative breast cancer as well as the effect of the test upon a panel of 5 breast oncologists. Methods: Recommendations for adjuvant therapy (prior to RS) and actual administration of adjuvant therapy (after RS) for consecutive patients with ER positive breast cancer were recorded. Six months later, with the same clinical information, a panel of oncologists gave recommendations for adjuvant therapy with and without RS results (with a two month interval wash out period). Recommendations were graded on a scale from 1 to 10 (1- strongest against, 10 strongest for). Panel changes, rates of panel non- consensus, and confidence changes (absolute value difference in recommendation from “5”) in panel member recommendations were compared before and after knowledge of the RS. Results: There were 29 patients. Pre RS recommendations were for chemotherapy in 13 (45%) and against in 16 (55%). RS results altered the administration of chemotherapy in in 9 (31%) patients; 7 (54%) patients recommended for chemotherapy did not receive it, and 2 (13%) patients received chemotherapy after it was not initially recommended. The panel initially recommended chemotherapy in 12 patients (41.4%) and against in 17 (59%). RS results changed panel recommendations in 7 cases (24%); 5 (42%) changed to against and 2 (12%) changed to for chemotherapy after test results. The RS reduced non-consensus recommendations of the panel by 10% and changed the confidence in 95 of 145 (65%) of panelist’s recommendations- 55% of which were decreased. Conclusions: RS resulted in chemotherapy administration changes in 31% of actual patients and 24% of panelist’s recommendations using the same medical information. The RS reduced non-consensus recommendations among the panelists but did not improve confidence. The opinions expressed here are those of the authors and do not reflect the official policy or position of the U.S. Navy, Department of Defense, nor the U.S. Government. No significant financial relationships to disclose.
Clinical and immunologic effects of a HER2/<i>neu</i> (E75) peptide vaccine booster in previously vaccinated breast cancer patients
Authors: J. P. Holmes, A. Amin, C. E. Storrer, A. M. Smith, Y. H. Jama, A. McNeil, D. Craig, S. Ponniah, G. E. Peoples
Journal: Journal of Clinical Oncology (2007)

3014 Background: We are conducting clinical trials of the HER2/neu E75-peptide vaccine in clinically disease-free breast cancer (BCa) patients. Our Phase I/II trials have shown that the E75+GM-CSF vaccine is safe and effective in stimulating clonal expansion of E75-specific CD8 + T-cells. Since peptide vaccines may not lead to long term immunity, we have assessed the need for and response to a vaccine booster for patients after completion of their primary vaccination series. Methods: BCa patients enrolled in our E75 vaccine trials who were &gt;6 months from the completion of their primary vaccination series were offered a single 1000 mcg dose of E75 peptide with 250 mcg of GM-CSF. Patients were monitored for local and systemic toxicity. E75-specific CD8 + T-cells were quantified using the HLA-A2:IgG dimer before and after booster administration. Results: 19 patients have received the vaccine booster. Median time from primary vaccine series was 12 months (range 6–25) and median residual E75-specific immunity was 0.61% (range 0- 3.43%). Significant residual immunity (SRI=CD8 + E75-specific T-cells &gt;0.5%) was seen in 71% of patients &lt;12 months from primary vaccination vs. 33% of patients ≥12 months. Graded local toxicities were as follows: 18/19 (94.7%) grade 1; 1/19 (5.3%) grade 2. Only 6/19 (31.6%) experienced even grade 1 systemic toxicity. Local reactions were more robust in patients receiving the booster &lt;12 months from primary vaccine compared to those ≥12 months (99±2.8 mm vs. 75±1 mm, p=0.01). In patients lacking SRI, 80% showed increased specific immunity post-vaccination. In these patients, the average CD8 + E75-specific T-cells pre-booster vs. post-booster was 0.37±0.03% vs. 1.06 ± 0.14% (p=0.07). Conclusions: The HER2/neu peptide vaccine E75 stimulates specific immunity in disease-free BCa patients. However, only about half of patients show SRI at median follow-up of 12 months. A vaccine booster is safe and highly effective in stimulating E75-specific immunity especially in those patients without SRI. Initial results suggest that the booster should be given within a year of completion of the initial vaccine series. No significant financial relationships to disclose.
Preliminary results of a phase II trial to examine the safety and efficacy of porfimer sodium photodynamic therapy (PDT) in locally advanced biliary tract carcinoma (BTC)
Authors: S. P. Pereira, K. Ragunath, J. Devlin, H. M. Meadows
Journal: Journal of Clinical Oncology (2005)

4180 Background: Phase II/III data from Germany suggest that PDT with porfimer sodium (Photofrin) is effective in maintaining biliary drainage and improving survival and quality of life in patients with irresectable cholangiocarcinoma. The aim of this study was to evaluate the safety and feasibility of delivering PDT to patients with locally advanced (T3/T4) BTC. Methods: Eligible patients had irresectable, histologically confirmed disease, a Karnofsky performance status (KPS) of ≥30% and life expectancy >12 weeks. Patients received 2mg/kg porfimer sodium (Photofrin) iv 48 hrs before endobiliary laser activation and stent replacement. Patients were assessed clinically before discharge on day 7 and radiologically on day 28. Results: 36 patients were entered over an 18 month period: 14M:22F, median age 65 (30–79) yr, median KPS 80 (50–100). Five patients experienced grade 3 toxicity: 3 biliary sepsis (days 7–28), 1 photosensitivity (day 28), and 1 pain (day 7). 29 patients had assessable response at day 28 (5 patients died pre-assessment and 3 not yet assessed): 6 partial responses, 14 stable disease and 9 progressive disease. Median follow-up in the 31 patients who survived >28 days was 7.6 months (range 0–21), during which time there were 11 further deaths, 10 due to BTC and 1 due to myocardial infarction in a patient with stable disease 3 months post-PDT. The median time to death was 11.2 months (range 2.5–17.3), Conclusions: Photofrin PDT can be delivered safely to patients with BTC and is suitable for testing in future phase II/III studies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Axcan
Potent suppression of proliferation of carcinoma cells by a novel non-nucleoside reverse transcriptase inhibitor.
Authors: Alexander Fisch, William Schroeder, Robert Smart, Osman Patel
Journal: Journal of Clinical Oncology (2015)

367 Background: The treatment of choice for many patients with advanced carcinomas is surgery in combination with aggressive chemo- and radiotherapy. Unfortunately, even with the aggressive regime of therapy against carcinomas, there is neither guarantee of life-long remission nor of further spread to other organs including the urogenital system. However, recent advances have identified the reactivation of telomerase as a pivotal element in the development of cancer. Therefore, the objective of this study was to evaluate the efficacy of a novel anti-telomerase (GV6) developed at our Institution on MCF7 (ER + , PR + , HER2 + ) and MDA-MB 231 (ER-, PR-, HER2-) cell lines. Methods: Seeded flasks (T-75) were supplemented with 25μm GV6 (n=4-6) or solvent alone (control, n=3) for 14 (short-term) or 27 (long-term) days. Cell viability and replicative senescence were both assessed using the Trypan Blue (Gibco) and SA-β-Gal (Cell Signaling Tech) methods, respectively. Results: By day 27, MCF7 flasks had a greater (p&lt;0.05) number of viable cells (35.4% vs. 29%) compared to MDA-MB 231 cells. More senescent cells were observed in GV6 supplemented MDA-MB 231 (~75%) cells than in MCF7 (~60%) by day 27. Conclusions: Our results indicate that GV6 is an equally potent inhibitor of telomerase and merits further studies.
Correlation between prior therapeutic dendritic cell vaccination and the outcome of patients with metastatic melanoma treated with ipilimumab
Authors: L. Pierret, S. Wilgenhof, J. Corthals, T. Roelandt, K. Thielemans, B. Neyns
Journal: Journal of Clinical Oncology (2009)

e20006 Background: Ipilimumab (Ipi) is an anti-cytotoxic T lymphocyte associated antigen 4 (CTLA4) IgG1 monoclonal antibody active against metastatic melanoma. Ipi acts by reinforcement of CTL-activation trough B7/CD28 receptor stimulation. A pre- existing anti-tumor CTL repertoire, induced by dendritic cell (DC) vaccination, could influence the therapeutic effect of Ipi. The influence of prior DC-vaccination on the outcome of melanoma patients (pts) treated with Ipi at a single center was analyzed to evaluate this hypothesis. Methods: Data were obtained from the medical files of pts treated at the UZ Brussel with Ipi in protocols CA184–022, -025, and the BMS Ipi medical need program. Ipi (0.3, 3 or 10 mg/kg) was administered iv q3 wks x4 q12 wks thereafter. Results: 20 pts (10M/10F; med age 51y, range 28–72) were identified. Prior therapy: autologous DC-vaccine loaded with melanoma associated antigens (14 pts) ± IFN-a2b (9/14 pts), cytotoxic agents (17 pts). Baseline characteristics: AJCC st IV melanoma (20 pts); baseline LDH &gt; ULN (16 pts). Ipi dose: 0.3 mg/kg (4 pts), 3 mg/kg (2 pts), 10 mg/kg (14 pts). Serial LDH measurements were available for 17 pts; 4 types of LDH-response following Ipi administration were observed: increase (11 pts), decrease (1 pt), fluctuation (4 pts), stable (1 pt). Objective response according to mWHO or irWHO: 3 PR, 1 SD, 16 PD. One pt received 0.3 mg/kg of Ipi (CA184–022) and had SD but no LDH response; at PD she received DC-vaccine and subsequently 10 mg/kg Ipi (medical need program) resulting in a fluctuating LDH-response and regression of an orbita-metastasis. Increasing LDH values following Ipi were less often observed in pts with prior DC-vaccination (5/6 pts (83%) without prior DC-vaccination had increasing LDH-values vs 6/12 pts (50%) with prior vaccination). DC- vaccination also correlated with regression of metastases and disease control (3/15 pts (20%) who were vaccinated had a PR/SD vs 1/6 (17%) PR for those who had not received prior DC-vaccinations). Conclusions: These data represent a small sample size from a single institution; however, our results suggests a potential correlation between prior therapeutic DC vaccination and outcomes in advanced melanoma patients treated with ipilimumab. [Table: see text]
Intracranial metastasis from nasopharyngeal carcinoma: Report of three cases and review of literature
Authors: J. S. Lau, W. Yeo, Y. L. Chan, W. Chan, P. Hui, S. F. Leung, W. K. Kwan, A. T. C. Chan
Journal: Journal of Clinical Oncology (2004)

5608 Background: Brain metastasis (mets) from nasopharyngeal carcinoma (NPC) is a controversial entity. Only 2 cases had ever been reported and no cohort study performed. Methods: We reviewed the clinical follow-up of a cohort of 1124 NPC cases first seen in our institute from 1993 to 2000, and identified 3 cases with intracranial mets on follow-up. All 3 patients received whole brain radiation therapy (WBRT) for the brain mets. Results: Case #1: A 45-year-old man presented with Stage T1N2M0 disease in 1996. In 2001, disease recurred in the neck and was inoperable. Static disease was achieved with chemotherapy. 1 year later, he experienced vertigo. Contrast CT brain revealed enhancing cystic lesions in both cerebellums. Histology of the lesion revealed metastatic undifferentiated carcinoma, staining positive for Epstein-Barr virus-encoded RNA (EBER). He received WBRT and remained alive at the most recent follow-up, which was 1 year after the diagnosis of brain mets. Case #2: A 51-year-old man presented with T2bN2M0 disease in 1997. At 32 months follow-up he was found to have mets in the lungs, liver and bone. Partial response was achieved with chemotherapy. 3 months later, he complained of right-sided weakness. MRI of brain showed multiple cystic metastatic lesions in both cerebral hemispheres. He underwent WBRT but died of progressive lung disease 4 months afterwards. Case#3: A 68-year-old man presented with Stage T1N3bM0 disease in 1994. At 33 months follow-up, he presented with unsteady gait. MRI of brain revealed lesions in right cerebellar hemisphere and left occipital lobe. Biopsy confirmed undifferentiated carcinoma consistent with mets of NPC. Despite WBRT, he succumbed 2 months later of progressive disease. Review of the 2 cases previously reported in the literature showed that the brain mets were located in the occipital lobes. Conclusions: Based on the present cohort study, the estimated frequency of brain mets from NPC is 3/1124 (0.26%). They may present as the first and only site of distant metastases. They typically present as cystic lesions in the cerebellum and/or occipital lobes. One case had survived more than one year after cranial RT. No significant financial relationships to disclose.
Analysis of outcomes in patients (pts) with recurrent ovarian clear cell carcinoma (ROCCC): Time to rethink our approach to treatment.
Authors: David Shao Peng Tan, Tzyvia Rye, Colin Barrie, Patricia Shaw, Stephane Laframboise, Anthony W. Fyles, Lisa Wang, Charlie Gourley, Amit M. Oza
Journal: Journal of Clinical Oncology (2014)

5548 Background: Advanced stage primary OCCC is associated with a poor prognosis following primary surgery and chemotherapy, but scant data exists regarding response rates (RR = RECIST PR/CR), progression free (PFS) and overall survival (OS) following treatment (rx) for ROCCC. Methods: We conducted a retrospective review of pts with ROCCC treated at 2 cancer centres to evaluate RR, clinical benefit rate (CBR=PR/CR or SD with PFS ≥12wks), PFS (time from start of rx to RECIST/clinical PD) and OS (time from 1st relapse after primary rx to death) following rx, and response/ symptomatic benefit after palliative radiotherapy (PRT). Platinum (plt) resistance was defined as PD < 6mths after plt. Results: In total, 137/256 pts developed ROCCC. Recurrences by FIGO stage at diagnosis were: Stage 1A/B (15/49, 29%), Stage 1C (16/67, 24%), Stage 2 (40/62, 65%), Stage 3 (46/54, 85%), Stage 4 (20/21, 91%), p<0.0001. Pts received a median of 1 line (range = 1-6, total = 166) of rx with an overall RR of 13/142 (9%) evaluable lines of treatment. Across all rxs, median PFS was 11 wks (95% CI: 8,14) and median OS was 40 wks (95% CI: 28,52). At 1st relapse, 72/86 treated pts were evaluable for response with RR=14% (10/72), CBR=31% (22/72) and median PFS=12wks (95% CI: 9,15). At 2nd relapse, 36/42 treated pts were evaluable for response with RR=8% (3/36) and CBR=33% (12/36) and median PFS=14wks (95% CI: 8,20). No significant PFS difference was observed for plt-sensitive pts treated with plt-based or non-plt-based rx at 1st relapse (HR=1.2; 95% CI: 0.6, 2.5; p=0.57) or at any relapse (HR=0.9; 95% CI: 0.4, 1.7; p=0.65). Outcomes for all rxs are shown in the Table. 6/12 (50%) pts derived benefit following PRT. Conclusions: ROCCC is a chemoresistant disease with a short median OS of 10mths. PRT offers symptomatic benefit. More clinical trials to identify effective systemic rxs for ROCCC are urgently required. Individual rx outcomes across all lines of rx. Rx N Plt Sensitive No. evaluable CR/PR% CBR% Median PFS wks Plt-based 63 Yes (46) 38 18 39 17 No (17) 14 14 36 11 Paclitaxel 8 7 0 14 8 Gemcitabine 7 7 14 14 4 Doxorubicin 29 25 4 16 10 Antiangiogenic agents 15 13 8 46 14 Topoisomerase inhibitors 30 27 4 19 8 Hormonal therapy 8 6 0 17 12 Others 6 5 0 0 11
Serum hyaluronic acid and collagen type IV as markers of hepatic fibrosis in patients with haemochromatosis and other chronic liver diseases American Association for the Study of Liver Diseases (AASLD) 50th annual meeting. Texas, USA. November 5-9, 1999.
Authors: G.A. Ramm, T.L. Murphy, P.A. Fanning, A.D. Clouston, G.J. Anderson, D.H. Crawford
Journal: Hepatology (1999)
Epsilon aminocaproic acid (EACA) is effective in controlling thrombocytopenic hemorrhage in patients with hematologic malignancies
Authors: R. V. Tiu, S. R. Kalmadi, C. Lowe, R. Sobecks, B. Bolwell, A. Lichtin, M. Kalaycio, J. Maciejewski, A. Advani, M. Sekeres, B. Pohlman
Journal: Journal of Clinical Oncology (2005)

6648 Background: Thrombocytopenic hemorrhage is a frequent side effect of chemotherapy in patients with hematologic malignancy that requires platelet transfusions. Transfusions incur risks of transmission of blood related pathogens, alloimmunization, and transfusion related reactions. EACA is a drug that works by inhibiting fibrinolysis. Methods: We reviewed our experience with EACA in patients with hematologic malignancies. We conducted a computer database search of all patients older than 18 years old with hemorrhage and platelets less than 75,000/μ l. Results: We identified 64 patients with hematologic malignancy treated with EACA. The median age was 54(range 23–83 years). There were 36 males and 28 females. Underlying diagnosis includes Acute Leukemia (N=40), Non-Hodgkin’s Lymphoma (N=9), Myelodysplastic syndrome (N=7), and others (N=8). The sources of bleeding included Mucosal (N=25), GI (N=23), GU (N=7), Pulmonary (N=4), CNS (N=3) and Venous Catheter Associated (N=2). Alloimmunization was evident in 29(45%) of the patients. The median platelet count at the initiation of EACA was 6,500/μ l (range = 1,000–61,000/μ l), the median duration of EACA administration was 10.5 days (range = 1 - 216 days). Median initial dose was 4 grams/day (range 2 - 24). Median Ave. dose was 6 grams per day (range 2–24). Bleeding completely stopped in 41(64%) decreased in 11(17%) and did not stop in 12(19%). Prior to EACA, patients were on an average receiving 1.5± 0.8 platelet unit transfusions per day (range 0 - 3). Subsequent to EACA, patients received 1.0± 0.7 transfusions per day for the duration of time they received EACA (Range 0–3). The average decrease in daily transfusions was 0.5± 0.1 (Confidence interval 95% p<0.0001). Adverse effects attributable to EACA included worsening of liver function in 7 patients, genitourinary clots requiring discontinuation of drug in 3 patients, arrhythmia in 1 patient. No other serious side effects were observed. Conclusions: EACA is an effective drug in the treatment of thrombocytopenic hemorrhage in patients with hematologic malignancies with an over-all response rate of 81%. EACA also reduces transfusion requirements with manageable side effects. No significant financial relationships to disclose.
Docetaxel in combination with radiation in prostate cancer: A phase I dose-finding study
Authors: W. R. Berry, R. K. Fairbanks, R. H. Gersh, S. M. Mull, D. Ilegbodu, L. Asmar
Journal: Journal of Clinical Oncology (2006)

14649 Background: Docetaxel (D), one of the more active agents against prostate cancer, also enhances the effects of radiation therapy (XRT). However, there is little information on the tolerability of the addition of D to pelvic XRT. This Phase I multicenter study was conducted to determine the maximum tolerated dose (MTD) and toxicities of D when given in combination with pelvic XRT. Methods: Patients (pts) with PSA levels &gt;4.0 and &lt;8.0 ng/mL after radical prostatectomy who were referred for salvage XRT were treated at 3 dose levels of D: 10 mg/m 2 , 16 mg/m 2 , and 22 mg/m 2 . One treatment course consisted of D given on Day 1 of each 1-week cycle for 7 cycles with daily XRT administered at 180 cGy Monday–Friday. The 3+3 standard Phase I escalation rule was used to establish the MTD. Results: A total of 9 pts were treated, 3 in each cohort at 3 dose levels. Median doses in the 3 cohorts were 22 mg, 35 mg, and 46 mg. Of the 9 pts, 89% were white, 89% had ECOG PS of 0, and 56% had Stage III disease. The median age was 56 years (range, 48–71). Eight patients completed all 7 weeks of D and XRT; 1 pt went off study after Week 4 due to a fall and fractured arm; 3 other pts subsequently went off study due to PD. In the 3 rd cohort, 1 pt had Grade 3 diarrhea (a predefined dose-limiting toxicity [DLT]). The cohort was not expanded by 3 additional pts, and the study was closed to enrollment. The MTD of D with concurrent XRT was not determined. The most frequent adverse events (AEs) were fatigue and diarrhea (67% each), nausea and proctitis (44% each), and anorexia and insomnia (22% each). Except for fatigue, the incidences of these AEs were as expected for treatment with D. Four patients (44%) had a CR (1 CRu). There were 4 PR (1 PRu; 44%) and 1 SD (11%). The median time to response was 1.88 mo. (range, 1.8–7); the overall survival was 27.5 mo.; and the median progression-free survival was 17.7 mo. (range, 1.8–27.5). All patients are currently alive. Conclusions: This Phase I study did not allow definition of the MTD of weekly D with XRT before the trial was terminated. The maximum dose tested was 22 mg/m 2 /week for 7 weeks. D with pelvic XRT to the prostate was well-tolerated and showed promising responses. It thus deserves further study in Phase II trials. Supported in part by sanofi-aventis, Bridgewater, NJ. [Table: see text]