bluuebunny/crossref_metadata_2025_split huggingface dataset:
ST03: A randomized trial of perioperative epirubicin, cisplatin plus capecitabine (ECX) with or without bevacizumab (B) in patients (pts) with operable gastric, oesophagogastric junction (OGJ) or lower oesophageal adenocarcinoma.
Authors: Smyth Elizabeth C , Langley Ruth E , Stenning Sally P , Stevenson Laura , Allum William H. , Grabsch Heike , Alderson Derek , Riddell Angela M , Crosby Thomas , Mason Robert , Griffin Michael , Mansoor Wasat , Evans Linda , Middleton Gary William , Seymour Matthew T. , Falk Stephen , Smith David , Sumpter Katherine Anne , Blazeby Jane M , Cunningham David 
Published: March 2020

TPS4143 Background: Perioperative ECX chemotherapy is a standard of care for localised gastric/OGJ/lower oesophageal adenocarcinoma (Cunningham NEJM 2006). B is a monoclonal antibody targeting VEGF-A, and in combination with chemotherapy results in improved response rates (RR) and progression free survival in advanced gastric cancer (Ohtsu JCO 2011). The aim of ST03 is to assess the safety and feasibility (stage I, first 200 pts) and efficacy (stage II) of the addition of B to perioperative ECX chemotherapy. Methods: ST03 is a multicentre, open-label, phase II/III randomised trial ongoing at 92 UK centres; sites in Germany will open in 2012. Eligibility criteria are histologically proven, untreated, resectable, lower oesophageal, OGJ or gastric adenocarcinoma; age ≥18 years; WHO PS 0-1; and adequate cardiac ejection fraction (EF). Exclusion criteria are TIA/CVA or MI ≤1 year; uncontrolled hypertension; ≥Grade II NYHA heart failure; recent gastrointestinal inflammatory conditions or major surgery/trauma/open biopsy <28d of study entry. Pts receive 3 pre- and 3 postoperative ECX (epirubicin 50 mg/m2 iv D1, cisplatin 60 mg/m2 iv D1 and capecitabine 1250mg/m2/D1-21) +/- B 7.5mg/kg D1 q3wk during chemotherapy, then 6 Bev q3wk (investigational arm). Surgery is pre-specified and laparoscopic procedures allowed only after quality assurance review. All specimens undergo central pathology review; blood and tissue collection for translational correlates is ongoing. The primary outcome measures for Stage I (safety results including cardiac EF) have been reported (Okines ASCO 2011). The stage II primary outcome measure is overall survival. Secondary outcome measures are RR, resection rate, disease free survival, toxicity, and QoL. An MRI substudy is open, a PET substudy is planned. 558 of ~950 pts required have been recruited, accrual expected to complete in 2013. An embedded pilot study within ST03 randomising HER2 positive patients to ECX ± lapatanib will open in 2012. Trial sponsored and co-ordinated by the MRC Clinical Trials Unit and funded by Cancer Research UK (CRUK06/025, NCT00450203).
Combination of antiangiogenic therapy and cytotoxic chemotherapy for sarcomatoid renal cell carcinoma.
Authors: Michaelson M Dror , McDermott David F. , Atkins Michael B. , Cho Daniel C. , Olivier Kara M. , Schwarzberg Abraham B. , Choueiri Toni K. 
Published: March 2020

4512 Background: Numerous treatment options exist for metastatic renal cell carcinoma (mRCC), but optimal treatment for patients (pts) with sarcomatoid features remains undefined. Sarcomatoid differentiation is a particularly unfavorable prognostic feature in mRCC. Cytotoxic chemotherapy has modest activity, with a response rate of 16% for doxorubicin plus gemcitabine (Gem). Retrospective data has suggested a response rate of 10% for antiangiogenic therapy. We prospectively studied the combination of antiangiogenic therapy, sunitinib (Su), with Gem chemotherapy in this mRCC subpopulation. Methods: Pts with mRCC and sarcomatoid differentiation were enrolled in a phase 2 clinical trial at 3 institutions. Treatment consisted of 21-day cycles of Su, 37.5 mg on a 2 weeks on/1 week off schedule, along with Gem 1000 mg/m2 on days 1 and 8. The primary endpoint was radiographic response rate (RR) by RECIST. Secondary endpoints included time to disease progression (TTP), safety, and overall survival (OS). Results: Among 35 pts treated in total, 7 were classified as MSKCC good risk, 26 as intermediate risk, and 2 as poor risk. There were 10 partial responses and 1 complete response, for a confirmed RR of 30%. An additional 10 pts exhibited stable disease (clinical benefit rate 60%). Among the 10 pts who had progressive disease as their best response, the majority had underlying non-clear cell histology. Median TTP was 3.5 months (range 0.5-12). Eight pts discontinued due to adverse events (AEs). The most common treatment-emergent grade 3 or higher AEs were neutropenia (8 pts), fatigue (5), anemia (2), and hypertension (2). No treatment-related deaths occurred. Median OS was 11 months (range 1-38+). Conclusions: To our knowledge, this is the largest prospective trial combining cytotoxic chemotherapy and antiangiogenic therapy in patients with RCC and sarcomatoid features. Our results suggest that combination therapy may be more efficacious than either treatment alone in this subtype of mRCC and supports an ongoing intergroup trial (NCT01164228). Further research is necessary to define prognostic factors, including histologic and molecular biomarkers, for distinct subpopulations within this heterogeneous disease. Clinical trial information: NCT00556049.
Multiplex testing of driver mutations in non-small cell lung cancer (NSCLCs) of African-American (AA) patients.
Authors: Gadgeel Shirish M. , Cote Michele L , Schwartz Ann G. , Bollig-Fischer Aliccia , Land Susan , Wenzlaff Angie , Chen Wei , Wozniak Antoinette J. , Sukari Ammar , Mantha Laura , Bepler Gerold 
Published: March 2020

7561 Background: Recently driver genetic alterations have been identified in NSCLC that can be targeted for therapeutic interventions. Previous reports have suggested that rates of certain mutations may vary according to ethnic background. We conducted multiplex testing of NSCLCs of AA and white patients to assess variability in the mutation rates by race. Methods: We identified tumor tissues of 136 AA and 320 white NSCLC patients collected as part of three different institutional review board approved studies. Using the Sequenom MassArray system and a multiplexed panel, we analyzed tumor DNA for 214 oncogenic mutations in 26 genes previously identified in NSCLC. Estimated risk (Odds Ratios (OR)) of any mutation and specific gene mutations among AA patients compared to white patients were calculated after adjusting for age, sex, smoking status and histology (adenocarcinoma versus non-adenocarcinoma). Information on smoking status was unavailable on 46 patients and was not included in calculations of ORs for some genes (ORª). Results: The median age at diagnosis was 60 vs 66 years in AA vs white patients; 43% of AA patients and 66% of white patients were males; 69% of AA patients and 52% of white patients had adenocarcinoma; 66% of AA patients and 85% of white patients had stage I/II NSCLC and 10% of AA patients and 6% of white patients were never smokers. 43% of the AA patients and 47% of white patients had at least one mutation detected (OR = 0.78; 0.5-1.2). 19% of AA patients and 6% of white patients had more than 1 mutation detected (OR 2.3; 1.1-4.9). AA patients were more likely to harbor mutations in STK11 (LKB1) (OR=8.4; 3.2-21.8) and NOTCH1 (ORª=8.1; 2.2-30.8), and they were less likely to have MET mutations (ORª= 0.12; 0.02-0.9) then white patients. While not statistically significant, AA had lower prevalence of Kras mutations (OR=0.64, 0.3-1.4) and p53 mutations (OR= 0.82; 0.4-1.6). Conclusions: Our analysis of NSCLCs shows that AAs were more likely to have multiple genetic mutations than whites and the mutation profile differs by race.
Concomitant chemoradiotherapy of cervical carcinoma.
Authors: Naizabekova Svetlana Shamshykeevna 
Published: March 2020

e16557 Background: In structure of cancer incidence among female population of Kyrgyzstan, cervical carcinoma takes the second place. incidence is 19.1 per 100 thousand of female population. growth of standardized cervical carcinoma index in Kyrgyzstan from 2002 to 2007 estimated as - 36.4% (from 14.0 to 19.1 per 100 thousand people). materials and methods. in the chemotherapy unit of the national center of oncology, ministry of health KR, from 2010 to 2012 were treated 51 patients with locally advanced cervical carcinoma IIb - stage IIIb with ftorafur as radiomodifier. all patients’ diagnosis were verified. histologically - squamous cell carcinoma. age of patients ranged from 29 to 74, median – 51 years. the main group consisted of patients with IIIb stage - 33 patients (64.7%), 18 patients with iib stage - 35.3%. all 51 patients with locally advanced cervical carcinoma received combined radiotherapy (external beam and intracavitary) on a radical program against ftorafur. ftorafur was taken orally dozed at 400 mg every 12 hours. absolute contraindications of use of ftorafur together with combined radiation therapy of patients with cervical carcinoma were not found. presence of severe comorbidity was one of the relative contraindication research results. evaluation of the effectiveness of the treatment was carried out according to WHO criteria, on the degree of regression of primary tumor. clinical results showed that complete regression occurred in 28 patients (54.9%), partial regression of the tumor in 16 patients (31.4%), stabilization of tumor in 7 (13.7%). objective response rates were 92.1%. side effects of the treatment were evaluated on a scale of toxicity (Common Toxicity Criteria NCIC). hematologic toxicity (anemia - 56.8%, leukopenia - 3,9%) I-II degree, gastrointestinal symptoms (nausea and vomiting - 3,9%) I-II toxicity. during the dynamical monitoring of patients, the III-IV toxicity stages were not found. conclusion. use of ftorafur as a radiomodifier together with concomitant radiation therapy on patients with locally advanced cervical carcinoma helped to accelerate the tumor regression. toxicity did not exceed I-II degrees. analysis of immediate results of treatment showed a high objective effect - 86.3% in the following category of patients.
Time to adjuvant chemotherapy (AC) in stage III colon cancer at a community cancer center: A quality improvement initiative.
Authors: Partridge Arun , Rother Mark , Enright Katherine , Kaizer Leonard , Myers Jeffrey A. , Quinton Cindy L. , Rajagopal Sudhashree , Strevel Elizabeth Laureen 
Published: March 2020

e17503 Background: The standard of care for stage III colon cancer remains 5FU based AC. In clinical trial settings, this begins within 56 days of surgery. Recently a meta-analysis suggested that delays to starting chemotherapy are associated with inferior outcomes and the goal should be to commence AC as soon as feasible. Our objective was to assess the time to starting AC for referred patients to our center and to identify modifiable factors which may be improve upon to reduce delays. Methods: All patients referred to our center with stage III colon cancer who received at least 1 cycle of intravenous AC between Jan.1, 2010 and Dec.31, 2010 were identified. Patient characteristics and time intervals between surgery, Medical Oncology referral, Medical Oncology consultation and initiation of AC were assessed. Results: The total number of patients is 43. Median time to initiation of AC from surgery was 60 days with a range of 29-118 days. Only 32% of patients commenced AC within 56 days of surgery. The intervals of time from surgery to Medical Oncology referral and Medical Oncology consultation to initiation of AC were similar with a median of 25 and 26 days respectively. The median time interval from Medical Oncology referral to Medical Oncology consultation was only 9 days. The bulk of the interval for initiation of AC after seeing a Medical Oncologist was for placement of central intravenous (CIV) devices which took a median of 19 days. Conclusions: The majority of our patients do not start AC within an accepted timeframe. Most of the delay is related to the interval taken to request a consultation to Medical Oncology by the surgeon and to Medical Oncology access to CIV devices. Educational programs geared to referring surgeons which stress the importance of timely AC can help and are being initiated. Further options such as pre booking CIV devices and colon cancer patient-specific nurse navigators to try and streamline the processes and reduce their delays are being explored. [Table: see text]
A cost-utility analysis of gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer.
Authors: Ko Yoo-Joung , Tam Vincent Channing , Mittmann Nicole , Pasteka Mark , Chan Kelvin K. 
Published: March 2020

e17569 Background: FOLFIRINOX has been shown to be superior to gemcitabine (gem) alone for metastatic pancreatic cancer (MPC) and has been established as the standard of care. A recent study (von Hoff et al, GI ASCO 2013) showed that gem + nab-paclitaxel (gem+nab-p) was superior to gem alone. The cost-effectiveness of gem+nab-p relative to gem or FOLFIRINOX has not been studied. Methods: A Markov cohort model was constructed for patients with MPC to examine the costs and outcomes of gem alone, gem+nab-p and FOLFIRINOX. Efficacy and side-effect data were obtained from pivotal phase III trials. Resource utilization data, unit costs and utilities were obtained from Ontario Ministry of Health and Long-Term Care, Sunnybrook Health Sciences Centre and the literature. The primary outcome was the incremental cost-effectiveness ratio (ICER) defined as cost per quality-adjusted life year (QALY). The analysis was conducted from the perspective of the Canadian public healthcare system over a 2-year time horizon adjusted to 2012 Canadian dollars (CAD$). Both cost and effectiveness were discounted at 5%. One way and probabilistic sensitivity analyses were performed. Results: Using gem as the base case, gem+nab-p had better outcomes but higher costs (see Table). The ICER was higher than conventional willingness-to-pay (WTP) threshold. Gem+nab-p was less effective but less costly when compared with FOLFIRINOX. It was dominated by combinations of gem and FOLFIRINOX (i.e. extended dominance), and therefore not cost-effective regardless of WTP threshold. If the price of nab-p was 20% lower, then gem+nab-p and FOLFORINOX would have similar cost-effectiveness. Conclusions: Gem+nab-p is not cost-effective, from the Canadian perspective, for the treatment of MPC based on the current price when compared with FOLFIRINOX. A lower-priced generic oxaliplatin, which is available in some jurisdictions including the United States, may affect the outcome of this analysis in further favor of FOLFIRINOX. [Table: see text]
Body mass index (BMI) influence on survival in adult patients with newly diagnosed acute myeloid leukemia (AML)/high-risk MDS: Retrospective study of 130 patients from a single institution.
Authors: Abdelfatah Mohamed , Al-Ameri Ali , Kanaan Zeyad , Malkawi Ahmed , Haller Nairmeen Awad 
Published: March 2020

e18011 Background: The incidence of obesity is increasing worldwide and is associated with numerous adverse health outcomes. In AML high body mass index (BMI) is associated with increased risk of treatment-related complications; the overall survival in patients with acute myeloid leukemia is inferior, with most studies conducted in the pediatric population. Aim: To evaluate the effect of increasing (BMI) in the overall survival (OS) of adult patients with AML/High risk MDS. Methods: After obtaining IRB approval, all adult patients with AML diagnosed and treated at our institution (2002–2010) were studied. Data collection included patient demographics, laboratory tests, bone marrow biopsies, BMI, and survival information. We classified the AML patients into two groups according to BMI (kg/m2) classification by WHO; normal Weight 18-25 kg/m2, overweight and obese >25 kg/m2. Chi-Square and T-test were used for between group comparisons and Kaplan-Meier test was applied for survival estimates. Results: Adult patients with newly diagnosed AML (n = 130) had a median age of 55 years (range: 19-90), and 43 (56%) patients were older than 75 years. Seventy-two patients (55%) were male and 58 (45%) were female. 45 patients (35%) in total had complex cytogenetics, 20 patients (15%) had AML arise from MDS.Forty-four patients (34%) were considered normal weight; Eighty-six patients (66%) were classified as overweight or obese. Overall median survival was 28 weeks; patients with BMI 18-25 kg/m2 had a 36-week median survival, while patients with BMI <25 kg/m2 had a 25-week median survival (p<0.499). Conclusions: Overall survival was low in the study population; survival in obese and overweight patients (BMI>25) was slightly lower than normal weight group (18-25 kg/m2), although this did not translate into a survival benefit. Future large scale studies may be needed to further define the role of BMI in survival benefit for these patients.
Clinical characteristics, treatment, and survival outcomes in malignant pleural mesothelioma: A institution experience in Turkey.
Authors: Kucukoner Mehmet , Kaplan Muhammed Ali , Inal Ali , Urakcı Zuhat , Abakay Ozlem , Tanrıkulu Abdullah , Abakay Abdurrahman , Senyigit Abdurrahman , Isikdogan Abdurrahman 
Published: March 2020

e18544 Background: Malignant pleural mesothelioma (MPM) is a aggressive tumor that causes high mortality. Treatment of MPM remains disappointing, even new approaches are present today. Methods: The present study retrospectively examined the data related to 150 patients with MPM who were examined and treated in our center in Turkey from 2005 to 2012. The aims of this study were; to investigate clinicopathologic characteristics, treatment modalities and potential prognostic factors. Results: There were 87 males (58%) and 63 females (42%), 92 of the patients (61.3%) had an asbestos contact and this contact was generally environmental. Surgical resection (EPP or P/D) was used in 32 patients, 87 patients (58%) received only chemotherapy. The median progression free and overall survival (PFS and OS) for all patients were 10.6 and 14.8 months. There was no statistically significant difference between the patients who received pemetrexed/cisplatin (54 patients) and gemcitabine/cisplatin (28 patients) regimens in terms of the PFS and OS (p=0.145, p=0.244). The comparison between patients who were operated on and those who were not did not reveal any statistical difference in PFS and OS (p=0.416, p=0.095). There was no difference in both PFS and OS rates in comparison of patients who had P/D or EPP (p=0.87, p=0.652). Log rank analysis, ECOG performance status (p=0.018), histology (p<0.001), stage (p<0.001) and leukocytosis (p=0.005) were found to be significant prognostic factors in OS. At multivariate analysis, ECOG performance status (p=0.016), and stage (p<0.001) remained independently associated with OS. Conclusions: In survival analysis revealed significant differences in terms of both the PFS and OS, performance status, histology, stage and leukocytosis. EPP or P / D surgical options did not provide difference in term of survival. Survival rates in patients who received combining platinum analogues with pemetrexed or gemcitabine as front-line chemotherapy were found similar.
A pilot feasibility study to evaluate the efficacy of lapatinib in eliminating HER2-positive tumor cells circulating in peripheral blood of women with metastatic breast cancer.
Authors: Agelaki Sofia , Kalykaki Antonia , Markomanolaki Haris , Kallergi Galatea , Kalbakis Kostas , Mavroudis Dimitrios , Georgoulias Vassilis 
Published: March 2020

e22105 Background: EGFR and HER2 are expressed on CTCs from pts with breast cancer (BC). In this study we aimed to evaluate the efficacy of lapatinib, a dual EGFR and HER2 TK inhibitor, to eliminate HER2+ CTCs in metastatic BC. Methods: Pts with metastatic disease and HER2+ CTCs detected after disease stabilization or response to prior therapy were eligible. Pts received lapatinib till disease or CTC progression, whichever occurred first. Cytospins of peripheral blood mononuclear cells (PBMCs) were double stained with HER2 or EGFR along with cytokeratin antibody; 106 PBMCs/pt were analyzed for each molecule. Results: Twenty-two pts were enrolled; median age was 62.5 yrs, 2 had HER2+ primary, 12 (54.5%) had visceral disease and 8 (36.4%) had received ≥3 lines. Treatment was discontinued in 1 pt before the end of the 1st cycle due to toxicity and 1 withdrew consent after 3 cycles. A total of 119 courses were administered [median 4.0 (range, 0.5-26.0)]; disease evaluation revealed SD in 11 pts and PD in 10. HER2+ CTC counts declined in 18 (85.7%) pts during treatment [median time to nadir 1 mo (range, 1 – 5)]. After the 1st cycle, HER2+ CTCs decreased in 14 (66.7%) pts, increased in 6 (28.6%) and remained stable in 1 (4.7%). At baseline, 3444 HER2+ CTCs were detected (median 130), whereas after the 1st and 2nd cycles, 2281 (median 1) and 989 (median 2), respectively, were identified. The difference between baseline and post-1st or post-2nd cycle CTC counts was significant for all pts and for patients with SD but not in progressing pts. EGFR expression on CTCs was evaluated at the baseline and the end of treatment sample; in 6 of 8 pts with CTCs detected at both time points, the % EGFR+ CTCs/pt increased from a mean of 29.72% to 71.52%. Moreover, the % ratio of EGFR+ among the total CTCs increased from 17.08% to 37.59%. Conclusions: Lapatinib is effective in decreasing HER2+ CTCs in pts with metastatic BC, irrespective of the HER2 status of the primary. EGFR+ CTCs increase during treatment implicating EGFR as a possible resistance mechanism. The above results suggest that tailoring therapy according to targets present on CTCs represents an effective therapeutic strategy in BC. Clinical trial information: NCT00694252.