tbuckley/cabot-search huggingface dataset:
A phase II trial of single-agent vinflunine as second-line treatment for advanced non-small cell lung cancer (An International Oncology Network Study, #I-05–009)
Authors: M. Joppert, M. Knapp, S. R. Dakhil, R. V. Boccia, R. Steis, C. M. Jones
Journal: Journal of Clinical Oncology (2008)

19033 Background: Single-agent vinflunine has activity in a variety of tumors. This Phase II single-arm study was designed to evaluate the safety and efficacy of vinflunine given every 3 weeks to patients (pts) with advanced NSCLC who have progressed after prior treatment with a platinum-based doublet. The primary endpoint is 1-year survival. Methods: Pts ≥ 18 years with confirmed advanced NSCLC (stage IIIB with malignant pleural effusions or stage IV) who have progressed after receiving a platinum-based doublet as first-line therapy, received vinflunine (320 mg/m2) as a 20-min IV infusion on day 1 of each 21-day cycle. Results: At the time of analysis, 60 pts have received study treatment and 70 pts have been enrolled (of a planned total of 75). Pts characteristics include: male/female, 43/27; median age 65.1 years (range 42–86); ECOG PS 0/1/2, 27/40/3; and Caucasian/Black, 67/3. The median number of cycles was 2 (range 1–22). One-year survival is 25%. Median survival is 6.1 months (95% CI, 3.1 to 8.8). There were no CRs, though 4 pts had a PR for an overall response rate of 10.5% (95% CI, 2.9 to 24.8). The most common G3 toxicities (NCI CTC v 2) were neutropenia (13.3%), fatigue (11.7%), abdominal pain (8.3%), constipation (8.3%), dehydration (8.3%), vomiting (6.7%), asthenia (5%), anorexia (5%), dyspnea (5%) and ileus (5%). The most common G4 toxicities were neutropenia (20%), change in mental status (5%), pulmonary embolism (3.3%), asthenia (3.3%) and respiratory failure (3.3%). There have been 15 deaths: 6 PD, 4 respiratory failure, 1 heart disease, 1 CVA, 1 sepsis and 2 from unknown causes. Conclusions: These results suggest that vinflunine has a manageable safety profile when used as a single agent for second-line treatment of pts with advanced NSCLC. Our preliminary results demonstrate an efficacy profile comparable to other studies of single agents for the second-line treatment of advanced NSCLC. No significant financial relationships to disclose.
EBV- DNA Viral Load in Peripheral Blood Mononuclear Cells of Patients with Chronic Lymphocytic Leukemia Is Associated with Unfavorable Prognosis
Authors: Jacek Rolinski, Ewelina Grywalska, Marcin Pasiarski, Agnieszka Stelmach-Goldys, Agata Surdacka, Maciej Maj, Stanislaw Gozdz
Journal: Blood (2014)
Phase II study of preoperative chemotherapy plus bevacizumab with early salvage therapy based on FDG-PET response in patients with locally advanced gastric and GEJ adenocarcinoma.
Authors: Elizabeth Won, David Ilson, David Paul Kelsen, Vivian E. Strong, Heiko Schöder, Yelena Yuriy Janjigian, Manish A. Shah, Daniel G. Coit, Murray F. Brennan, Marinela Capanu
Journal: Journal of Clinical Oncology (2013)

94 Background: Response on FDG-PET scan during preoperative chemotherapy has prognostic significance. PET non-responders do poorly whether they continue the same chemotherapy or proceed directly to surgery [JCO 24: 4692; 2006, Lancet Onc 8:797;2007) Early identification of treatment failure using PET scan may spare patients (pts) from inactive therapy and allow for cross-over to alternative therapies. We performed a phase II trial to examine the effectiveness of FDG-PET directed early switching to salvage chemotherapy measured by 2 year disease free survival (DFS) in the PET non-responding group. Methods: Pts with PET avid, EUS and laparoscopically staged T3 or Node positive resectable gastric or GEJ adenocarcinoma received induction with epirubicin 50mg/m2, cisplatin 60mg/m2, capecitabine 625mg/m2 bid days 2-21(ECX) and bevacizumab 15mg/kg day 1. PET scan was repeated at week 3. PET responders (≥35% decline in SUV) continued ECX for 2 more cycles. PET non-responders switched to 2 cycles of salvage therapy: docetaxel 30mg/m2 d1, d8 q21 days, irinotecan 50mg/m2 d1, d8 q21 days and bevacizumab 15mg/kg day 1. Pts had surgery 4 weeks after cycle 3. Results: 20 of planned 60 pts were enrolled before the study closed for poor accrual. 14 male (64%), 8 female (39%), median age 62, median KPS 90. 11(55%) had a PET response after the first cycle. 10/11 (91%) underwent R0 resection: 1/10 pathologic CR, 3/10 pathologic PR. 9/20 PET non-responders switched to the salvage regimen. 7/9 Non-responders had R0 resection, none achieved a pathological response. The DFS for PET responders was 27.8mos (95% CI 10.3-27.8) and DFS in salvage group has not been reached. There was no significant difference in DFS between the two groups (p= 0.4). Follow up for overall survival is ongoing. Biologic correlative studies are pending. Conclusions: Response on PET scan during induction chemotherapy can identify early treatment failures. The results for therapy cross-over indicate a potentially improved DFS with salvage chemotherapy. Results from this trial are hypothesis generating and merit evaluation in a larger clinical trial. Supported by a grant from Genentech. Clinical trial information: NCT00737438.
30-day mortality of surgeries in disseminated cancer patients: An analysis using NSQIP, dividing surgeries into low, medium, and high risk.
Authors: Tony Pesavento, Xiang Fang, Armour R. Forse, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2012)

e16554 Background: This study is the first comprehensive analysis of surgical outcomes in disseminated cancer patients. Methods: We analyzed the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) 30-day mortality data for major surgeries on 3,250 disseminated cancer patients and 144,199 patients who did not have disseminated cancer. Results: The most common procedures performed on disseminated cancer patients include a partial removal of the colon (354 patients), a partial removal of the liver (302 patients), a partial removal of the small intestine (169 patients), and an exploration of the abdomen (159 patients). The 30-day mortality for surgeries for cancer patients can be divided into low risk (&lt;3%), moderate risk (3-15%), and high risk (19-44%) as shown in the table. Low risk surgeries done non-emergently include mastectomy, partial removal of the liver, repair of the bowel opening. Moderate risk done non-emergently include removal of the small intestine, bowel to bowel fusion, colon removal, and partial removal of the colon. High risk include non-emergent exploration of the abdomen, and the following emergency surgeries: bowel to bowel fusion, removal of the colon, removal of the small intestine, cholecystectomy, or partial removal of the colon. Conclusions: The 30 day operative risk for disseminated cancer can be divided into low, medium and high risk surgeries. All surgeries done in an emergency setting have a 30 day mortality of greater than 15%. Mastectomy, partial removal of the liver, repair of the bowel opening all have a 30 day mortality of less than 3%. [Table: see text]
Outcome of active surveillance prior to systemic target therapy in patients with metastatic renal cell carcinoma.
Authors: Nobuaki Matsubara, Hirofumi Mukai, Yoichi Naito, Kuniaki Itoh
Journal: Journal of Clinical Oncology (2013)

444 Background: The clinical course of metastatic renal cell carcinoma (mRCC) has a wide spectrum that ranges from indolent to rapidly progressive disease. Initial active surveillance (AS) followed by deferred systemic target therapy might be a treatment option in a subpopulation of patients with indolent mRCC. However, very few studies have been published about AS and its outcome as well as potential predictive factor that might be associated with indolent mRCC. Here, we report clinical outcomes of mRCC patients who initially were monitored by AS. Methods: We retrospectively reviewed and analyzed the clinical and pathological data of mRCC patients who initially were monitored by planned AS prior to systemic therapy due to asymptomatic or slowly progressive disease at National Cancer Center Hospital East between 2000 and 2011. The primary outcome measures were progression-free survival (PFS) and overall survival (OS). Results: A total of 29 patients were eligible for this analysis. The median age at diagnosis was 69 years, and all patients had a good general condition with a performance status of 0 or 1. A total of 65% of patients had recurrent disease and 35% were in stage 4. All of the patients had undergone nephrectomy, and 86% had clear cell carcinoma. None of the patients was categorized into a poor risk group according to both MSKCC and Heng criteria. The median follow-up period was 35.4 months. During the follow-up period, disease progression was observed in 72% of patients but only 14% died. The median PFS time was 26.1 months. After disease progression was observed, only 58% of these patients received treatment or intervention. The median OS have not been reached yet, but 12, 24 and 48 months OS rates were 96.4, 88.7 and 83.8%, respectively. Conclusions: PFS and OS of patients who underwent AS were extremely favorable. For these indolent subpopulations, AS might be a treatment option, so toxic and expensive systemic target therapy could be deferred for a significant period of time without prognostic disadvantage. However, further observational study with a larger sample size might be needed in order to identify the exact subpopulation eligible for AS.
Amiloride effects on abiraterone antiproliferative activity in prostate cancer cells in vitro and on clinical management of abiraterone induced mineralocorticoid excess syndrome.
Authors: Francesca Valcamonico, Francesca Bedussi, Diego Galli, Alberto Dalla Volta, Martina Fragni, Sara Vezzoli, Vittorio D. Ferrari, Barbara Lazzari, Laura Ferrari, Francesco De Ferrari, Maurizio Memo, Alfredo Berruti, Sandra Sigala
Journal: Journal of Clinical Oncology (2016)

175 Background: Abiraterone acetate (AA) deeply inhibits androgen synthesis but leads to an ACTH driven increase in mineralocorticoid hormones requiring glucocorticoid supplementation that may impair its antineoplastic efficacy. New strategies for the management of the AA induced mineral corticoid excess syndrome (MCES) are warranted. Methods: We analyzed in vitro the interaction in terms of proliferative activity of AA plus/minus prednisone with the steroid aldosterone receptor antagonists: eplerenone, spironolactone, a non-steroidal aldosterone receptor antagonist (PF-03882845) and the epithelial sodium channel antagonist amiloride. LNCaP were grown in a medium with charcoal-treated serum and concentration-response curves for each studied drug were performed. Besides, the activity of amiloride plus hydrochlorothiazide was assessed in the clinical management of AA induced MCES in 5 consecutive patients with castrate resistant prostate cancer. The recovery of AA induced MCES symptoms and signs was the primary end point. Results: Prednisone, spironolactone and eplerenone induced an increase in the LNCAP proliferation rate and antagonized the AA-induced reduction of the cell proliferation in a concentration-dependent manner, while PF-03882845 did not. Amiloride at high concentrations induced cell death. When combined with AA +/- prednisone, amiloride at low concentration did not interfere with AA anti-proliferative activity however an additive inhibitory effect was observed at higher concentrations. The association of amiloride with hydrochlorothiazide led to a complete disappearance of all clinical and biochemical signs of abiraterone induced MCES in the 5 treated patients. Conclusions: Amiloride and PF-03882845 do not negatively interfere with the AA inhibition of proliferative activity of prostate cancer cells in vitro. The association of amiloride plus hydrochlorothiazide is efficacious in the management AA induced MCES.
Cost-effectiveness of metal stents in pancreatic cancer.
Authors: Alberto J. Montero, Lisa M. Meckley, Ayanna M. Anene, Tanya G.K. Bentley, Jesse D. Ortendahl, Jose M. Martinez
Journal: Journal of Clinical Oncology (2014)

260 Background: American Society for Gastrointestinal Endoscopy guidelines recommend endoscopic metal stent placement for pancreatic carcinoma patients with biliary obstruction and estimated life expectancy of &gt;6 months. Because life expectancy of many such patients has until now been &lt;6 months, plastic stents are frequently placed. Recent phase III trials demonstrated that compared with current standards of care, treatment with chemotherapy regimens FOLFIRINOX and gemcitabine/nab-paclitaxel significantly prolonged overall survival (OS) well beyond the 6-month range. Given this prolonged survival, we evaluated the cost effectiveness of initial metal versus plastic stent placement in pancreatic adenocarcinoma patients with biliary obstruction. Methods: A Markov cohort model was developed to project lifetime health-related outcomes, costs, quality-adjusted life years (QALYs), and cost effectiveness of metal compared with plastic stents. Patients entered the model with locally advanced cancer and underwent endoscopic retrograde cholangiopancreatography with metal or plastic stent placement. Patients were at risk of complications, stent migration or occlusion with subsequent stent placement, progression to metastatic cancer, and death. Published sources were used to estimate clinical, cost, utility, and event rate inputs, and results were presented from the 3 rd party payer perspective in 2012 U.S. dollars/QALY. In sensitivity analyses, overall survival was varied from 6-24 months to assess the impact of uncertainty in estimates on model outcomes. Results: Patients with metal stents had lower costs and greater overall and quality-adjusted survival. Placement of metal stents saved approximately $1,500 per patient over a lifetime, improving OS by 0.07 months and quality-adjusted survival by 0.10 months. These findings were robust in sensitivity analyses varying the length of survival for patients with pancreatic cancer. Conclusions: This model demonstrates that placement of metal biliary stents at initial onset of obstructive jaundice in patients with stage III/IV pancreatic adenocarcinoma is cost saving and improves survival when compared with use of plastic stents.
Basal sFAS/sFASL ratio and FAS polymorphisms, as a prognostic marker, in advanced colorectal carcinoma patients (ACRC), treated with oxaliplatin-based chemotherapy
Authors: P. Gascon
Journal: Journal of Clinical Oncology (2005)

3631 Background: FAS (CD95) has been implicated in DNA-damage sensitivity. We have previously shown that decrease of sFAS/sFASL ratio correlates with acquired chemotherapy-resistance (Nadal et al. Proc. ASCO 2004). We analyzed now the influence of basal sFAS/sFASL ratio and FAS gene polymorphisms in the promoter region, on survival. Methods: Eligible criteria included; patients with ACRC and ECOG performance status (PS) 0–2, treated with first-line oxaliplatin-based chemotherapy. A maximum of 6 months of therapy was planned. CT scans were done every 3 months until progressive disease. ELISA sFAS and sFASL analysis were done before therapy. FAS -1377 and -670 gene polymorphism was tested using PCR-RFLP method in genomic DNA extracted from peripheral blood. Results: From July 2001 to September 2003, 67 patients were included. Median age 63 (33–80), 61% male, 81% ECOG (PS) 0–1. With a median follow-up of 26 months, median progression free survival was 9 months and median survival time was 20 months. Median basal sFAS/sFASL ratio was 80.8 ng/ml. We found a significant association between sFAS/sFASL ratio and survival. Patients with ratio ≥80.8 ng/ml survived a median time of 13 months (95% CI 10–16) compared with 30 months (95% CI 17–42) of patients with ratio <80.8 ng/ml (p=0.002). We didn’t found a significant association between FAS -670 gene polymorphism and survival. Patients with GG homozygous genotype survived a median of 22 months (95% CI 13–32), compared with, those have homozygous AA genotype 20 months (95% CI 11–28) or heterozygous GA genotype 19 months (95% CI 4–33), respectively (p=0.84). ECOG PS (p=0.0007) but not serum LDH concentration level (>1UNL) (p=0.23) was also significant predictors for survival. Conclusion: These data suggest that high basal sFAS/sFASL ratio could identify a group of ACRC patients with poorer prognosis. No significant financial relationships to disclose.
A study of the combination of oxaliplatin, capecitabine, and herceptin (trastuzumab) and chemoradiotherapy in the adjuvant setting in operated patients with HER2+ gastric or gastro-esophageal junction cancer (TOXAG study).
Authors: Huseyin Abali, Suayib Yalcin, Huseyin Cem Onal, Faysal Dane, Berna Oksuzoglu, Nuriye Ozdemir, Huseyin Mertsoylu, Mehmet Artac, Celalettin Camci, Bulent Karabulut, Fatma Bugdayci Basal, Burcin Budakoglu, Mehmet Ali Nahit Sendur, Burce Goktas, Fatih Ozdener, Arzu Calisgan
Journal: Journal of Clinical Oncology (2016)

TPS182 Background: Trastuzumab in combination with chemotherapy has been shown to prolong survival of HER2+ esophago-gastric cancer patients. The primary aim of our study was to evaluate safety and tolerability of trastuzumab (T) in combination with oxaliplatine (O), capecitabine (C) and radiation (R) therapy in the adjuvant setting in curatively resected esophago-gastric cancer patients. Methods: Forty patients with IB or higher stages was planned to be recruited and here we report the interim analyses on 22. We would consider the study positive if at least 64.4% of patients could tolerate the therapy. Eligible patients received T 8 mg/kg intravenously (iv) on Day 1 of cycle 1 and 6 mg/kg iv on day 1 of every following 3-weekly cycle for 1 year as 17 cycles, with O 100 mg/m2 iv on Day 1 of cycles 1-3 and C 850 mg/m2 orally twice daily on days 1-14 of cycles 1-3 and on 5 days per week during chemo-radiotherapy. R was given at a total dose of 45 Gy divided into 25 doses on 5 treatment days per week for 5 weeks starting from the 1st day of cycle 4. Results The median age was 57.5 years (Min-Max: 35-74). Of 22 patients; 15 were male (68.2%), 21 (95.5%) had an ECOG PS score ≤ 1, 21 (95.5%) had D2 lymph node resection. There were 11 serious adverse events. Two patients died on therapy; 1 secondary to pulmonary thrombo-emboli, and the other had to cerebral ischemia (thought to be due to Behçet’s disease), and 7 died of progression. There were 6 dose reductions (1 for T, 2 for O and 3 for C), T was stopped in 1 patient, C was interrupted 8 times (mostly during radiotherapy). Patients who have completed 3 cycles of O, C, T and 4th and 5th cycles of chemo-radiation therapy with C and T were defined as tolerable. Out of 22 patients, 19 (86.4%) were tolerable (Chi Square test: p = 0.0623). Median survival time for interim analysis patients (n = 22) was 22 months (95% CI: 11-23 months). Conclusion T in combination with O, C and chemo-radiation with C and T was tolerable with the tolerability rate of 86.4%, in curatively resected HER2 + esophago-gastric cancer adjuvant treatment. Clinical trial information: NCT01748773.
Evaluation of serum vascular endothelial growth factor (VEGF) levels following trans-arterial chemoembolization (TACE) of hepatic malignancies of gastrointestinal (GI) origin
Authors: S. Roy-Chowdhury, Y. Peng, D. Wei, R. Modzelewski, H. Zeh, D. Bartlett, C. Brown
Journal: Journal of Clinical Oncology (2005)

3087 Background: TACE is an effective modality in the treatment of metastatic or primary hepatic malignancies of GI origin. One outcome from this effective therapy is hypoxia and cell death with tumor necrosis. Inflammation induced by necrotic cells and hypoxia due to the embolization process are potential stimulators of VEGF production. VEGF is a potent angiogenic cytokine, and secretion of this factor can lead to increased tumor angiogenesis, thereby offsetting the goal of therapy. In this study, we measured serum VEGF levels before and after chemoembolization of hepatic malignancies. Additionally, serum uric acid levels are measured as a correlate of tumor necrosis. Methods: 14 patients, 18 years or older, with primary or secondary malignancies confined to the liver, were included. 10 ml of blood was collected from patients before and at various time points following chemoembolization. All blood samples collected were grouped in one of the 5 groups: pre, 24 hr post, early post (>1 day & < 1 week), intermediate post (≥1 week & < 4 weeks), and late post (≥4 weeks). The 14 patients received a total of 24 treatments, and data was analyzed using two-tailed paired T-test. Results: Serum VEGF levels were significantly increased at 24 hr post-TACE (mean increase of 57%, p=.0005). There were increases at the intermediate and late time points, but these differences were not statistically significant when compared to the pre-TACE levels (p=0.074 and 0.067, respectively). At late time points, serum uric acid levels demonstrated a mean increase of 11% (p=0.03). Serum uric acid levels at the other time points were not significantly changed from the pre-TACE levels. Conclusions: Serum VEGF level is increased following TACE for hepatic malignancies of GI origin and may be the result of multiple factors: hypoxia and tumor necrosis. The increased VEGF secretion may stimulate angiogenesis and promote tumor regrowth, suggesting a potential role of combining antiangiogenic therapy with current TACE protocols in the treatment of hepatic malignancies. No significant financial relationships to disclose.
HLA-cw polypmorphism and killer cell immunoglobulin-like receptor (KIR) gene analysis in Korean patients with colorectal cancer.
Authors: Hyung Jin Kim, In Kyu Lee, Won-Kyung Kang, Jung Hyun Kwon, Seong-Taek Oh
Journal: Journal of Clinical Oncology (2012)

525 Background: Many kinds of genetic and environment factors are involved in colorectal cancer development. Natural killer cells (NK cells) play important roles to protect from viral infections and the early development of cancers, and it is activated or inhibited by killer cell immunoglobulin-like receptors (KIR) which bind to HLA class I. KIR genes are encoded on chromosome 19q13.4. And there are 7 kinds of activating KIRs, and another 7 kinds of inhibiting KIRs. The genetic polymorphisms of KIR genes effect the expression of KIR on NK cells, and there are ethnic differences. In this study, we were trying to investigate the KIR genotype of Korean colorectal cancer patients. Methods: DNAs were extracted from the peripheral bloods from normal populations and Korean colorectal cancer patients. KIR genes were amplified using PCR-SSP methods, and HLA-Cw genes were characterized using PCR methods. The results were analyzed between cancer patients and normal control group. Results: KIR2DL2 and KIR2DS2 were found at low rate and KIR2DL3 were found at high rate compare to the Eastern studies, but the rates were similar with Japan study. In this study, KIR2DS5 (33.2% vs. 20.8%, p-value&lt;0.007) was increased in colorectal cancer group, and in rectal cancer subgroup, KIR3DL1 (93.2%, vs. 98.1%, p-value&lt;0.05), KIR2DS2 (7.8% vs. 19.5%, p-value&lt;0.01), KIR2DS4 (93.2% vs. 98.1%, p-value&lt;0.05) were decreased significantly. HLA-Cw6 (9.1% vs. 15.7%, p-value&lt;0.05) and HLA-Cw7 (17.4% vs. 27.7%, p-value&lt;0.02) were decreased in colorectal cancer group, but no difference was found when they were classified to HLA-C1 and HLA-C2 group. Among the patients with HLA-C1 homozygote, KIR2DS2 was decreased significantly (5.8% vs. 14.5%, p-value&lt;0.004). Conclusions: There are ethnic differences of KIR genotypes. KIR2DS5 is increased in Korean colorectal cancer patients, and in rectal cancer subgroup, KIR3DL1, KIR2DS2 and KIR2DS4 are decreased, so there are immunologic differences between colon and rectal cancers. And among the patients with HLA-C1 homozygote, KIR2DS2 is decreased. Therefore KIR2DS2 in presence of their ligand (HLA-C1 group) may have protective effect against colorectal cancer.