tbuckley/cabot-search huggingface dataset:
Gemcitabine-based chemotherapy in advanced-metastatic and/or unresectable pancreatic cancer
Authors: G. F. Samelis, A. Areovimata, F. Matsiakou, G. Zografos, P. Papakostas
Journal: Journal of Clinical Oncology (2005)

4274 Introduction: Advanced and/or unresectable pancreatic cancer is a lethal disease with a median survival lasting no longer than two months. Many chemotherapeutic regimens are investigated with newer drug-combinations, in order to improve responses and quality of life. Materials and Methods: 16 men and 8 women with histologically proved inoperable or metastatic adenocarcinoma of the pancreas were eligible for the study. The median age was 65 (range 35–81) years old. 14 out of 24 patients (pts) had performance status (PS): 0, 6 pts had PS: 1, and 4 pts had PS: 2. 11 patients received docetaxel: 75mg/m2 day 1 in combination with gemcitabine 1100mg/ m2 d1+d8 in a 3 week cycle (group A). 8 pts received gemcitabine 1100mg/ m2 d1+d8 in combination with paraplatine AUC: 5, d1 in a 3 week cycle (group B). 5 patients received monotherapy with gemcitabine 1100mg/ m2 d1+d8+d15 in 4 week cycle (group C). Patients received in total 112 chemotherapeutic cycles, 51 cycles in group A (median: 4.6, range: 1–9), 38 cycles in group B (median: 4.7, range: 2–6), 23 cycles in group C (median: 4.6, range 1–8). Results: 3 out of 11 patients (27%) had stable disease (SD) (group A), 4 out of 8 patients (50%) had SD (group B), and 3 out of 5 patients (60%) had SD (group C). The rest of the patients progressed. In total we observed 10 (41.6%) patients with stable disease with a median time to progression of 6 (range: 1–18) months. Toxicity grade III included: anemia in 2 patients (8.3%), granulocytopenia in 1 patient (4%) and thrombocytopenia in 1 patient (4%). Grade I-II toxicities reported in 5 (21.1%) patients with anemia, 3 (12.5%) patients with granulocytopenia, one patient (4%) had fever and 3 (12.5%) patients had alopecia. No toxic death was reported. Patients’ survival lasted until 36 months with a median survival of 7.89 (range: 1–36) months in all the three group-arms. Many patients reported amelioration in their pain-scale and performance status. Conclusion: Gemcitabine based chemotherapy offered a stability of their disease in 41% of the patients with a median time to progression of 6 months (range: 1–8) and a median survival of 8 months (range: 1–36) respectively. Also, it improves the quality of life in patients with inoperable and/or metastatic pancreatic cancer. No significant financial relationships to disclose.
Abstract 18556: Trends in Door-to-Balloon Time and Mortality in STEMI Patients Undergoing Primary PCI in Massachusetts
Authors: Murtuza J Ali, Katya Zelevinsky, Sharon-Lise T Normand, Ann Lovett, Zoran S Nedeljkovic, Alice K Jacobs
Journal: Circulation (2012)

Background: Recognition that primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for ST-elevation myocardial infarction (STEMI) if delivered in a timely fashion resulted in national efforts successful in reducing time to treatment. To determine whether the decreasing door-to-balloon (DTB) time is associated with a reduction in mortality, we evaluated 12,210 STEMI patients undergoing primary PCI in Massachusetts between 1/2005 and 9/2010. Methods: We used prospectively collected data compiled, audited, and analyzed by the Massachusetts Data Analysis Center, the state mandated PCI registry. Results: The mean age of the population was 61.9 years, with 29% women and 6.1% in cardiogenic shock. Between 2005 and 2010, median door-to-balloon time decreased from 85.0 to 67.5 minutes in patients presenting directly to PCI hospitals and from 153.5 to 113.0 minutes in patients requiring inter-hospital transfer for PCI. DTB time ≤90 minutes increased from 56.8% to 77.1% in patients presenting directly to PCI hospitals and from 4.3% to 23.4% in patients requiring inter-hospital transfer (Table). However, in-hospital and 30-day mortality during the study period did not significantly change (Figure). Conclusion: DTB time has decreased for STEMI patients in Massachusetts and more patients are achieving the guideline-recommended DTB ≤ 90 minutes. Despite these improvements, in-hospital and 30-day mortality remain unchanged. The reason for the unexpected absence of a decrease in mortality will require further study.
Early undetectable serum PSA is an independent predictive factor of progression-free survival (PFS) and bone metastases in patients with localized prostate cancer treated by androgen deprivation and radiotherapy
Authors: K. Fizazi, K. Slimane, F. Eschwege, P. Wibault, R. De Crevoisier
Journal: Journal of Clinical Oncology (2004)

4684 Background: Patients with locally-advanced prostate cancer are managed by androgen deprivation (AD) and radiation (RT). We attempted to identify early predictors of outcome in a large retrospective series with a long follow-up. Methods: From 1991 to 1998, 92 patients with locally-advanced prostate cancer were treated by AD and RT. Median pretreatment PSA level was 19 ng/mL (1.6–148). Clinical stage was T1 (4%), T2 (60%), and T3 (36%). Gleason score was 4–6 (46%), 7 (32%) and 8–10 (22%). Prognosis was classified as high risk (T3 and/or PSA>20 ng/mL and/or Gleason score > 7) (n= 59) or intermediate risk (n= 33). AD consisted in a complete androgen blockade (GnRH agonist and anti-androgen) (55 pts) or an anti-androgen as a single agent (37 pts) and was given for a median duration of 6 months (3–18). AD was usually initiated 3 months before RT. The prostate was to receive 65 Gy (2.5 Gy/day) (74 pts) or 70 Gy (2 Gy/day) (18 pts). The median follow-up was 70 months (14–126). Results: The 5-year PSA-PFS rate was 41% (95% CI : 30–51) and 57% (95% CI: 47–68) according to the ASTRO definition and the MDACC definition, respectively. The 5-year metastases-free survival and the 5-year cause-specific survival rates were respectively 82% (95% CI: 73–89) and 94% (95% CI: 88–99). The median PSA level assessed 3 to 6 months after the start of AD and before RT was 1.3 ng/mL (0.08–31). In multivariate analysis, significant predictors for PSA-PFS included high-risk disease (p<0.01) and an undetectable (<0,2 ng/mL) serum PSA after 3 months of neo-adjuvant AD (p<0,01). These two factors were also independent predictors of distant metastases (p=0.04). Conclusions: An undetectable serum PSA 3 months after AD is an independent predictor of both PSA-PFS and distant metastases in locally-advanced prostate cancer. Therefore, this factor may be a useful early surrogate endpoint in clinical trials using neo-adjuvant treatments. No significant financial relationships to disclose.
The impact of a delay in initiating radiation therapy on prostate-specific antigen outcome for patients with clinically localized prostate cancer
Authors: P. L. Nguyen, R. Whittington, S. Koo, D. Schultz, K. B. Cote, M. Loffredo, E. McMahon, A. A. Renshaw, J. E. Tomaszewski, A. V. D'Amico
Journal: Journal of Clinical Oncology (2004)

4503 Background: While a delay in initiating external beam radiation therapy (RT) following diagnosis is known to decrease local control in patients with breast or head and neck cancer, its effect on PSA outcome in prostate cancer is unknown. Methods: We studied 460 patients who received 3D conformal RT without hormonal therapy for clinically localized prostate cancer from 1994–2001. The primary endpoint was PSA failure (ASTRO definition); estimates of PSA control were made using the Kaplan-Meier method. Delay was defined as the time between diagnosis and RT start date. Cox multivariable regression was used to determine the ability of treatment delay to predict time to PSA failure after adjusting for the distribution of baseline PSA, clinical T-category, Gleason score, and percent of cores positive for tumor. Results: Treatment delay independently predicted for time to PSA failure (p=0.013) after controlling for baseline PSA, clinical T-category, Gleason score, and percent of cores positive. Patients with high-risk disease (n=161) had 5-year estimates of PSA-failure free survival of 53% vs. 38% (Plog-rank=0.037) for those with delay less vs. greater than the median delay (2.5 months) respectively. Low-risk patients (n=299) had no detectable difference in PSA outcome (p=0.621) between those with a delay less vs. greater than the median delay (2.6 months). Conclusions: A treatment delay of approximately 3 months adversely affected PSA outcome for patients with high-risk but not low-risk disease following RT alone. Whether this effect remains after the use of RT plus concomitant hormonal therapy in patients with high-risk disease requires further study. No significant financial relationships to disclose.
Expression of galectin-3 in non-small cell lung cancer (NSCLC): Prognostic significance in adenocarcinoma
Authors: J.-H. Choi, H.-Y. Lim, J. S. Park, H.-W. Lee, Y. M. Jung, H. C. Kim, Y. T. Oh, H. Choi, S. C. Hwang, J. H. Han
Journal: Journal of Clinical Oncology (2005)

9671 Background: Expression of galectin-3, which belongs to a family of galactoside-binding proteins, has been associated with malignant transformation, cancer progression, and protection against apoptosis in several malignancies such as breast cancer. Methods: We investigated the expression of galectin-3 and its association with clinicopatholgic characteristics including disease-free survival (DFS) and overall survival (OS) in 104 patients (pts) with locally advanced NSCLC who underwent surgical resection (stage II: 47, IIIA: 40, IIIB: 10, IV: 7) using immunohistochemistry. Eighty-two pts (79%) received adjuvant treatment (chemotherapy: 9, radiotherapy: 17, both: 56). Results: High expression of galectin-3 was observed in 46 pts (44%), which was significantly associated with adenocarcinoma (p=0.001) and large primary tumor size (>4 cm) (p=0.033). With a median follow-up of 45 months (20–114 months) in survivors, 4-year DFS and OS of total pts were 31% and 43%, respectively, excluding 6 deaths from postoperative complications. High expression of galectin-3 was not associated with poor DFS (p=0.233) or OS (p=0.391). However, in pts with adenocarcinoma (36 pts) or adenosquamous carcinoma (7 pts), high expression of galectin-3 was significant independent predictor of poor DFS (p=0.021) in addition to male gender (p=0.026) and advanced stage (p=0.013). Conclusions: High expression of galectin-3 was significantly associated with poor DFS in locally advanced NSCLC pts with adenocarcioma. No significant financial relationships to disclose.
BMI1, the Polycomb-Group Gene, Is Recurrently Targeted by Genomic Rearrangements in Progressive B-Cell Leukemia/Lymphoma.
Authors: Leila Rouhi, Natalie Put, Thomas Tousseyn, Julio Finalet Ferreiro, Wim De Kelver, Hilde Demuynck, Johan Verschuere, Ivan Théate, Carmen Vicente, Lucienne Michaux, Chris De Wolf-Peeters, Peter Vandenberghe, Jan Cools, Iwona Wlodarska
Journal: Blood (2009)
Preoperative induction chemotherapy with docetaxel-cisplatin followed by concurrent docetaxel-cisplatin and radiation therapy (RT) in patients with locally advanced esophageal cancer: Final results of the multicenter phase ll trial SAKK 75/02
Authors: J. C. Schuller, S. Balmer-Majno, W. Mingrone, V. Hess, R. von Moos, M. Borner, A. Schnider, D. Koeberle, R. A. Popescu, T. Ruhstaller
Journal: Journal of Clinical Oncology (2008)

4550 Background: The purpose was to investigate the efficacy, toxicity and feasibility of preoperative docetaxel-cisplatin together with RT in a multicenter setting. Methods: Eligibility criteria: resectable, locally advanced (uT3 or uN1, T4 if deemed resectable) squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the thoracic esophagus or gastroesophageal junction (Siewert type l); staged by EUS, CT and PET scan; age 18–70y; PS <2; normal organ functions. Treatment: 2 cycles of docetaxel 75mg/m2 and cisplatin 75mg/m2 q3w, followed by weekly ×5 docetaxel 20mg/m2 and cisplatin 25mg/m2 with concomitant 45 Gy RT in 25 fractions; surgery 3–8 weeks after RT. Simons two stage design was used. Primary endpoint was histopathological response rate according to Mandard (Cancer 1994). Results: 66 pts, 56 males, were included from 11 institutions; median age 61y (35–70y); AC 53%; SCC 46%; 9 pts (14%) had no resection (4 progressive disease, 4 medical reasons, 1 patient's refusal). Of 57 (86%) operated pts, 53 pts (93%) had RO-resection, 6 pts died due to complications after surgery (3 after > 30 days). Four pts needed a feeding tube before start of treatment and 2 during treatment. The most frequent grade 3/4 toxicity of chemoradiotherapy was Dysphagia in 21%. 32 pts (48% of all included pts) achieved complete or nearly complete histopathological remission (TRG 1 or 2), 19 SCC (64% of SCC) and 13 AC (34% of AC). After a median follow up of 29 months (CI: 24–32), median time to progression or death was 22.5 months (CI: 14.0–28.3). Median overall survival was 39.7 months (lower CI: 27.0). 27 pts (40%) are still alive and without residual or recurrent disease. Conclusions: This trimodality treatment shows encouraging antineoplastic activity with 48% histopathological responders, the survival data compares favorable with other trials and it is feasible in a community-based multicenter setting. In most cases, the insertion of feeding tubes during therapy was not necessary due to the induction chemotherapy. No significant financial relationships to disclose.
Clinical features, recurrence patterns, and treatment in endometrial stromal sarcomas: A 30-year, single-institution experience
Authors: G. El Maalouf, P. Duvillard, A. Rey, P. Morice, C. Haie-Meder, C. Lhommé, P. Pautier
Journal: Journal of Clinical Oncology (2008)

10574 Background: Low-grade endometrial stromal sarcomas (LG-ESS) are rare uterine malignancies characterized by their indolent evolution. Predictive factors of recurrences and value of treatment modalities are warranted. Methods: Clinicopathological variables, treatment modalities and outcomes of patients (pts) with LG-ESS, treated in our institution between 1978 and 2007, were retrospectively reviewed. Results: Pathologic diagnoses from 48 women were reconfirmed by a single pathologist. The median follow-up was 54 months [4–348], and 47 pts are still alive. FIGO Stage distribution was: stage I (n=28),II (n=4), III (n=11), and IV (n=5).Surgical treatment (n=47) included hysterectomy with or without bilateral salpingo-oophorectomie (BSO) in respectively 42 and 5 pts. 40 pts underwent complete resection (CR). 2 pts had positive pelvic lymph nodes. Post surgery treatments in CR population are reported in table 1. In CR population, 13 pts recurred with a 3-years recurrence-free survival rate of 79%. First sites of recurrences were pelvic in 7 pts, extra-pelvic in 2 pts, and both in 4 pts. In univariate analysis, poor prognosis factors of recurrence were: stage III/IV (p=0.04) and absence of BSO (p<0.001). The recurrence rate of pts with BSO was remarkably lower than that of patients without (22.8% vs. 100%, P<0.001). Among the 7 pts with incomplete resection (5 pts had positive surgical margins and 2 pts had lung metastasis), 3 pts treated with tamoxifene progressed rapidly and 3 among 4 pts treated with antiaromatase inhibitors had clinical benefit. Using immunohistochemistry, we detected positive oestrogen and progesterone receptors in 45 and 46 tumors respectively. Conclusions: 33 % of LG-ESS pts with primary complete resection develop pelvic (54%) and/or extra-pelvic recurrences (46%) within a median of 3 years. Predictive factors of recurrence were stage FIGO III/IV and absence of BSO. Among hormonal treatments, aromatase inhibitors seem to be the most active agents. Post Surgery treatment (N=40) Nb of pts Nb of recurrences Observation (4 pts without BSO) 21 9 BRP 7 0 BRP + chemotherapy 4 2 Antiaromatase inhibitors 7 1 Chemotherapy (without BSO) 1 1 BRP: Brachytherapy ± pelvic radiotherapy No significant financial relationships to disclose.
Phase II stopping rules employing response rates and early progression
Authors: J. R. Goffin, D. Tu
Journal: Journal of Clinical Oncology (2007)

2553 Background: Drug development in oncology has become increasingly resource intensive. Anything that might accelerate drug development would benefit patients and drug developers. Traditionally, tumour response rates (RR) have been used to assess the efficacy of new agents in phase II trials. High rates of early progression of disease (EPD) may also indicate lack of drug efficacy, and this endpoint has the potential to shorten trials compared to assessing RR alone. This work seeks to create a set of rules that will allow phase II drug assessment employing both RR and EPD. Previous work on this subject suffered from insufficient power, as determined by the authors [Freidlin et al, J Clin Oncol, 20:599, 2002]. Methods: Using TreeAge Pro Healthcare software, we created a computer model that would accept specified trial parameters and determine through simulations stopping rules based on observed number of responses and EPDs to achieve the desired power and alpha error for a single-armed two-stage study with 15 patients in each stage. The null hypothesis (H(nul)) specified the response rate (rr(nul)) and early progressive disease rate (epd(nul)) that would render a drug uninteresting for further development, such that: H(nul): rr LE rr(nul) &amp; epd GE epd(nul), where rr is that actual response rate observed and epd is the actual rate of early progression. Similarly, the alternate hypothesis (H(alt)) specified the response rate (rr(alt)) and early progressive disease rate (epd(alt)) that would render a drug interesting for further development, such that: H(alt): rr GE rr(alt) or epd LE epd(alt). (LE, less than, equal to; GE, greater than, equal to) Results: Conclusions: The simulation was able to establish stopping rules for observed number of responses and EPDs to achieve the desired error rates. Variations on the rules based on other trial sample types and design parameters will be detailed. [Table: see text] No significant financial relationships to disclose.
Noncoding miRNAs as novel prognostic factor for 5-fluorouracil adjuvant therapy in colorectal cancer
Authors: Y. Xi, A. Formentini, M. Kornmann, J. Ju
Journal: Journal of Clinical Oncology (2006)

3609 Background: The roles of non-coding miRNAs in tumorgenesis are just emerging. miRNAs regulate gene expression at post-transcriptional level by influencing translation efficiency of their target mRNAs. Previous studies from our laboratory have identified a number of miRNAs that were dis-regulated in colon cancer cell lines related to the loss of p53 tumor suppressor gene. In this study, the in vivo significance of some of these miRNAs was further evaluated using clinical samples. Ten miRNAs (hsa-let-7b, hsa-let-7g, hsa-miR-15b, hsa-miR-181b, hsa-miR-191, hsa-miR-200c, hsa-miR-26a, hsa-miR-27a, hsa-miR-30a-5p and hsa-miR-30c) were evaluated for their potential prognostic value in colorectal cancer patients receiving 5-fluorouracil (5-FU) based therapy. Methods: Forty eight snap frozen clinical colorectal samples (24 normal and 24 paired colorectal cancer patient samples) were selected with detailed clinical follow-up information. RNAs were isolated from these samples using TRIzol reagent. After cDNA synthesis with miRNA specific primers, the expression levels of 10 miRNAs were quantified via qRT-PCR analysis. The statistical significance of these markers for disease prognosis was evaluated using two tailed paired T-test. Kaplan-Meier survival curve was generated and followed by Logrank test. Result: Among the ten miRNAs, hsa-miR-15b (p=0.02), hsa-miR-181b (p=0.01), hsa-miR-191 (p=0.03) and hsa-miR-200c (p=0.005) were significantly over-expressed in tumors compared to normal colorectal samples. Kaplan-Meier survival analysis indicates that hsa-miR-200c was a significant prognostic marker for predicting patient’s survival (p=0.01). The patients (n=15) with higher hsa-miR-200c expression had shorter survival interval (median survival = 26 months) compared to patients (n=9) with lower expression (median survival = 38 months). Conclusions: Some of these miRNAs may function as oncogenes due to their over-expression in tumors. Hsa-miR-200c may be a potential novel prognostic factor for 5-FU based chemotherapy in colorectal cancer. No significant financial relationships to disclose.
Expression of ERCC1 and XPA has demonstrated that cisplatin is more toxic than oxaliplatin in oesophageal adenocarcinoma cells
Authors: R. K. Mehmood, K. M. Sales, S. Dijk, M. C. Winslet
Journal: Journal of Clinical Oncology (2005)

4251 Background: Xeroderma Pigmentosum protein A (XPA), recognises DNA damage, its low levels with decreased expression of Excision Repair Cross Complementing 1(ERCC1), an endonuclease of Nucletide excision repair pathway, were found responsible for pronounced cisplatin sensitivity. While increased levels of XPA and ERCC1has demonstrated cisplatin resistance. We want to compare the levels of XPA and ERCC1 gene expression in oesophageal adenocarcinoma cells (OE33) after treating them with cisplatin and oxaliplatin. Methods: Lethal doses 50 (LD50) of oxaliplatin and cisplatin in OE 33 cells for 24 hours were determined by the alamarBlue assay. Cells were treated with that LD50 at 2, 4, 6 and 24 hours. Using RT-PCR and specific primers, expression of ERCC1 and XPA gene levels with cisplatin and oxaliplatin treatments were compared at 2, 4, 6 and 24 hours interval, by Syngene Gene Tools programme. Results: XPA was undetectable with cisplatin treatment, while it was overtly expressed with oxaliplatin treatment at all time intervals. Small amounts of ERCC1 were seen in 2, 6 and 24 hours with below detectable levels at 4 hours after cisplatin treatment. In contrast, it was over expressed with oxaliplatin treatment at all time intervals Conclusions: XPA and ERCC1 were over expressed with oxaliplatin treatment while in cisplatin treatment they were nearly undetectable. These findings suggest that cisplatin is more toxic in oesophageal adenocarcinoma cells than oxaliplatin. No significant financial relationships to disclose.
Different subpopulations of circulating tumor cells in patients with hepatocellular carcinoma and clinical relevance.
Authors: Mingxin Pan, Xiaoping Xu, Zesheng Jiang, Guolin He, Chenjie Zhou, Jiasheng Qin, Yi Gao
Journal: Journal of Clinical Oncology (2015)

e15130 Background: The existence of circulating tumor cells (CTCs) in peripheral blood has a correlation with prognosis and tumor metastasis in patients with hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) is regarded as pivotal process in tumor metastasis, and plays an important role in tumor local invasion and subsequent dissemination. According to the EMT status, CTCs can be classified into different subpopulations, including epithelial CTCs, mesenchymal CTCs, hybrid (epithelial/mesenchymal) CTCs etc. Furthermore, the mesenchymal CTCs hold a strong metastatic potential. Methods: We isolated CTCs from peripheral blood of 13 HCC patients. The CanPatrol CTC enrichment technique (SurExam China) was used to enumerate and characterize the phenotypes of CTCs. The first step of this technique was to isolate CTCs via a filter-based method; then, a multiplexed mRNA fluorescence in situ hybridization method was used to characterize CTCs according to the expression status of epithelial and mesenchymal biomarkers. Results: Among the 13 patients, 12 patients had detectable CTCs. All CTC-positive patients had detectable hybrid CTCs, four CTC-positive patients had detectable mesenchymal CTCs, and one CTC-positive patient had detectable three phenotypes: epithelial, hybrid and mesenchymal CTCs. Of the four mesenchymal CTC-positive patients, three of them were undergoing metastasis, and it suggested that metastasis in patients with HCC was positive associated with mesenchymal CTCs (p < 0.01). Conclusions: Although the sample size of this study was small, our findings suggested that the existence of mesenchymal CTCs might have a positive correlation with tumor metastasis in HCC.