bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial to evaluate combination of folfox6 + bevacizumab in initially unresectable liver metastases from colorectal cancer (crc)
Authors: Malavasi N. , Dealis C. , Depenni R. , Zironi S. , Bertolini F. , Losi L. , Gerunda G. E. , Colucci G. , Luppi G. , Conte P. F. 
Published: March 2020

14603 Introduction: The gold standard treatment of CRC liver metastases is surgical resection. Bevacizumab has proved efficacy in advanced disease. Primary objective of the study is to evaluate resecability rate of liver metastases and incidence of major surgery complications. Secondary objective is to relate tumor and serum biomarkers (EGFR, VEGF, TS, Ki67, ERCC1, MSH2, MLH1 and VEGF ) to clinical outcome Methods: Baseline requires evaluation by CT-PET scan, biopsy of metastases; PET scan is needed after first administration to describe preliminary response. The treatment consists of FOLFOX6 regimen associated to Bevacizumab, 5mg/Kg, every two weeks; elective surgery is planned after 6 cycles (the last one excludes Bevacizumab dose) by CT-PET scan; if resection is appropriate, it will be performed, otherwise the treatment will continue to 12 cycles. Biomarkers are assessed at baseline, following the first administration and before surgery Results: Up to now 11 patients have been enrolled (M/F:6/5; median age:64, range:46–72); ECOG: 0/1. 10 patients reached surgical step while 1 patient is still on chemotherapy. Three patients (27%) were not suitable for resection and received further chemotherapy: 1 had PR, 1 PD and 1 became resectable after 12 cycles. In the other 7 patients (63%): 2 CR (18%) histologically confirmed; 4 macroscopic and curative resection of liver metastasis; 1 is receving two stage epathectomy (portal vein occlusion before major liver resection). Life threatening toxicities: 1 TVP causing discontinuation of Bevacizumab, 1 hospitalization for gastro-intestinal and G4 neutropenia both causing discontinuation of the whole therapy. Bevacizumab complications before major surgery did not occurred; 1 patient reported post operative delay wound healing. Less severe toxicities: haematological G3 in 2 patients (18%), G1 in 1 patient (9%); 3 gastrointestinal G2 (27%); neuropathic in 1 patient (9%). The VEGF serum decreased after the first dose of Bevacizumab in all specimens Conclusions: Systemic chemotherapy with combination regimens may downstage liver metastases and thus increase resecability rate without important surgery complications; biomarkers related to clinical outcome are in evaluation. No significant financial relationships to disclose.
Glufosfamide (GLU) plus gemcitabine (GEM) in pancreatic adenocarcinoma: Preliminary results of a phase 2 trial
Authors: Chiorean E. G. , Dragovich T. , Hamm J. , Barrios C. H. , Gorini C. F. , Langmuir V. K. , Kroll S. , Tidmarsh G. T. , Colowick A. B. , Loehrer P. J. 
Published: March 2020

15005 Background: Glufosfamide is glucose linked to isophosphoramide mustard, the active metabolite of ifosfamide. Cancer cells use glucose at a higher rate than normal cells, which may lead to preferential metabolic targeting by GLU. The Phase 1 study established a GLU dose of 4500 mg/m2 for the GLU + GEM regimen. The objectives of the Phase 2 part of this study are to evaluate the safety and efficacy of GLU+GEM in pts with pancreatic adenocarcinoma. Methods: Eligible pts had metastatic and/or locally advanced pancreatic adenocarcinoma previously untreated with chemotherapy, Karnofsky Performance Status =70, creatinine clearance (CrCL) =60 mL/min and acceptable hematologic and liver function. Pts received GLU 4500 mg/m2 iv over 4 hours on Day 1 and GEM 1000 mg/m2 iv over 30 minutes on Days 1, 8 and 15 of every 28-day cycle. CT scans were obtained every 8 weeks. Primary endpoint was response rate. Results: Twenty-nine pts were enrolled. One patient with ineligible histology was excluded from efficacy analyses. The 14 male/15 female pts had a median age of 59 years. Median cycles on treatment was 4 (range 1–10+) and 9 pts completed all 6 cycles. Six of 28 (21%; 95% CI: 8- 41%) pts had a partial response (duration 1.0+ to 5.8+ months), one unconfirmed. Ten of 28 (36%) pts had stable disease (median duration 5.3 months). Median progression-free survival was 3.7 months. Six-month survival was 54% (95% CI: 38–78%). Grade 3/4 neutropenia and thrombocytopenia occurred in 21/29 (72%) and 8/29 (28%) pts. Five pts (18%) had a GLU-related serious adverse event (SAE). Two pts died due to SAE unrelated to GLU. Three pts developed renal failure; two were GLU-related with evidence of renal tubular acidosis (RTA). One pt developed GLU-related SAE of RTA without renal failure. The CrCL fell below 60 mL/min in 7 of 27 (26%) pts with CrCL =60 at baseline. Conclusions: Preliminary data indicate that GLU + GEM may benefit pts with chemotherapy naïve pancreatic adenocarcinoma. [Table: see text]
Response evaluation with endoscopic ultrasound (EUS) measuring maximum tumor thickness to predict pathological response after neoadjuvant chemoradiation therapy (CRT) in patients with locally advanced esophageal cancer (EC)
Authors: Jost C. , Schuller J. C. , Meyenberger C. , Bauerfeind P. , Moosmann P. , Frossard J. L. , von Moos R. , Koeberle D. , Metzger U. , Ruhstaller T. 
Published: March 2020

15009 Background: EUS does not accurately assess T-stage after neoadjuvant CRT due to inflammation, necrosis and fibrosis. We evaluated whether maximum tumor thickness (MTT) can predict pathological response (tumor regression grade, TRG) after CRT. Methods: Patients (pts) with resectable, locally advanced EC, were treated with 2 cycles of docetaxel/cisplatin (DC) q3w followed by CRT (DC weekly x5 with concomitant 45 Gy radiation therapy) and surgery. Radial scan EUS (7.5MHz) measured MTT at baseline and 3–5 weeks after CRT completion. We prospectively hypothesized that MTT =6mm in the second EUS predicts complete and subtotal pathological response (TRG1 and 2), tested by logistic regression. The effect of >50% reduction of MTT was analysed as well. Results: 66 pts from 11 institutions were treated; median age 61y (35–70y); adenocarcinoma (AC) 53%; squamous cell carcinoma 46%; 40 pts were eligible for the EUS project (10 no surgery, 10 tumor stenosis prohibiting EUS, 5 MTT not measured, 1 intolerant to EUS). Initial EUS staging: 9 uT2N1, 3 uT3N0, 27 uT3N1, 1 uT3Nx; Siewert-type-1 in 13 of 22 AC. Reduction of MTT to =6mm correctly predicted TRG1/2 with sensitivity (sens) 45%, specificity (spec) 90%, negative predictive value (NPV) 62%, and positive predictive value (PPV) 82%, the Iogistic regression model showed a trend predicting response only (OR 0.80; C.I. 0.62–1.03; p=0.082). Reduction of MTT >50% predicted TRG1/2 with sens 40%, spec 75%, NPV 56% and PPV 62%. Conclusions: The absolute value of maximum tumor thickness =6mm in the second EUS correctly predicts a good response to CRT in 82% (spec 90%) - rather than the relative reduction of MTT >50% -, but does not identify all responders. Feasibility in this multicenter setting was limited by exclusions due to tumor stenosis and incomplete measurements. [Table: see text] No significant financial relationships to disclose.
Cancer stage at diagnosis, treatment, and survival among US- and foreign-born Asians and Pacific Islanders with gastric cancer
Authors: DaCosta Byfield S. , Earle C. C. , Li D. , Ayanian J. Z. , McCarthy E. P. 
Published: March 2020

15018 Background: Asians and Pacific Islanders (APIs) have increased risk of developing gastric cancer, but whether cancer treatments and outcomes vary by birthplace is unknown. We examined the association between birthplace and cancer stage at diagnosis, treatment, and survival comparing API and non-Hispanic white (NHW) patients. Methods: We studied 6840 NHW and 4485 API patients diagnosed with gastric cancer from the Surveillance, Epidemiology and End Results Program between 1992 and 2003. We used bivariable analyses to compare stage, receipt of adequate lymph node assessment and surgery across groups: US-born APIs, foreign-born (FB) APIs and NHWs. We used multivariable polychotomous logistic and proportional hazards regression models to determine differences between US-born and FB APIs compared to NHWs in cancer stage and survival, respectively. Models included age, marital status, tumor grade, location, and stage (survival only). Results: Of API patients, 29% were US-born, 49% FB and 22% of unknown birthplace. APIs were more likely than NHWs to present with earlier-stage diagnoses and receive surgery and adequate lymph node assessment (p<0. 001). After adjustment, US-born [aOR=0.86 (0.75–0.93)] and FB APIs [aOR=0.76 (0.68–0.84)] were less likely to present at later stages than NHWs. Among APIs, FB patients had fewer lymph node assessed than US-born (p<0.001), but were as likely to present with earlier stage disease and receive surgery. After adjustment, US-born [aHR= 0.90 (0.85–0.98)] and FB APIs [(aHR= 0.85 (0.78–0.92)] had higher survival rates than NHWs. Results were similar after adjusting for treatment. *p <0.001 for comparison with NHW +p>0.05 for comparison among API Conclusions: Compared to US-born APIs, FB API patients with gastric cancer present at later stages and are less likely to receive adequate surgical lymph node assessment. However, both US-born and FB API patients present at earlier stages and experience better survival than non-Hispanic white patients. [Table: see text] No significant financial relationships to disclose.
A study of the pharmacokinetics of 5-FU when S-1 was administered orally as an adjuvant agent in gastric cancer patients
Authors: Matsumoto H. , Hirai T. , Hirabayashi Y. , Kubota H. , Murakami H. , Higashida M. , Kawabe Y. , Urakami A. , Yamashita K. , Tsunoda T. 
Published: March 2020

15024 Background: S-1 is an effective oral anti-cancer drug which is formulation of 5-FU, and it is widely used for gastric cancers in Japan. However, the compliance of S-1 treatment is not satisfactory due to its side effects. We hypothesized that the plasma concentration of 5-FU could be verified individually, because the drug is administered orally. Therefore, we investigated the pharmacokinetics of 5-FU when it was administered orally in the form of S-1. Methods: The plasma concentration of 5-FU after S-1 oral administration for adjuvant chemotherapy was measured in 22 advanced gastric cancer patients (Stage II or III). Total gastrectomy was performed in 12 patients and distal gastrectomy was performed in 10 patients. All patients were given S-1 (80mg/m2) orally at 8:00 and 20:00, daily. Blood samples were collected at 10:00, 12:00, 14:00 and 16:00 on the 7th day after S-1 administration and we measured 5-FU concentration of plasma. Results: Pharmacokinetic parameters of plasma concentration of 5-FU were as follows: Cmax, 157.92 ± 42.9 ng/ml; Tmax, 2.36 ± 0.79 h; T1/2, 2.90 ± 2.36 h; and AUC 0–8 ,731.8 ± 236.4 ng ·h/ml in all patients given the usual dosage. The plasma concentration of 5-FU was quite different between patients. The difference of Cmax and AUC was 3∼ 4 times. The AUC0- 8 in the total gastrectomy patients (752.6± 273.3 ng·h/ml) was higher than that in distal gastrectomy patients (714.5±211.7 ng·h/ml), however this difference did not reach significance. Adverse events of more than grade 3 were observed in 7 patients. AUC0–8 of 4 of 7 patients were more than 800 ng·h/ml and those of 2 other patients were more than 750 ng·h/ml. The patients with high AUC0–8 levels had a tendency to show more severe adverse events. Conclusions: We conclude that physicians should pay close attention to individual differences in the plasma concentration of 5-FU in postoperative gastric cancer patients when this drug is given orally as S- 1. No significant financial relationships to disclose.
Cumulative false-positives (FP) in the prostate, lung, colorectal, ovarian (PLCO) cancer screening trial
Authors: Miller J. H. , Kramer B. S. , Kreimer A. R. , Prorok P. C. , Xu J. , Baker S. G. , Fagerstrom R. , Berg C. D. , Gohagan J. K. 
Published: March 2020

1503 Background: Multiple cancer screening tests have been advocated for the general population. However, providers and patients are not always well-informed of the burdens incurred by screening. We sought to determine the cumulative risk of a FP screen, and resulting diagnostic procedure risk, for an individual in a multiple modality screening program. Methods: Data were analyzed for a 3-year period from the intervention arm of the randomized PLCO Cancer Screening Trial. Eligible individuals were 55 to 74 years of age with no prior history of prostate, lung, colorectal, or ovarian cancer. Additional exclusion criteria were: 1) death before/refusal to take/missing all screens, and 2) less than 3-year follow-up. 68,415 participants were included. The control arm received “usual care.” Women randomized to screening were offered annual CA-125, transvaginal ultrasound, CXR, and baseline plus 3- or 5-year sigmoidoscopy (FSG). Men randomized to screening were offered annual digital rectal exam, PSA, CXR, and baseline plus 3- or 5-year FSG. Fourteen exams were possible for each sex over the study period. We defined a FP as a positive screen with no target cancer diagnosis after at least 3-years follow-up. Advanced adenomas (villous histology, severe cellular dysplasia, or =1cm in diameter) were considered true positives. Results: 42.6% (N=29,152) of participants had at least one FP. Using a geometric distribution model, the cumulative risk of a FP after 1 screen was 5.7% for men, and 2.2% for women. After 14 tests, the risk was 62.2% for men and 50.7% for women. Sensitivity analysis for FP risk after 14 tests by Kaplan-Meier method demonstrated a cumulative FP risk of 61.5% for men and 54.5% for women. The consequent cumulative risk of a diagnostic procedure was about 27% for men and 18% for women after 14 tests. Conclusions: For an individual participating in a multiple modality cancer screening trial, the risk of a FP exceeded 50% by the 14th test. Physicians should educate patients about the risks of FP tests and resulting diagnostic interventions when counseling about cancer screening regimens. [Table: see text]
Improved survival with radiation therapy in early pancreatic adenocarcinoma
Authors: Artinyan A. , Hellan M. , Mojica-Manosa P. , Ellenhorn J. , Kim J. 
Published: March 2020

15036 Background: Although chemoradiation is often used following pancreatic cancer resection, recent studies have questioned the role of radiation therapy in this setting. The objective of this study was to determine the effect of adjuvant radiation therapy following pancreatectomy in patients with node-negative (N0) pancreatic cancer. Methods: The Surveillance, Epidemiology, and End Results (SEER) registry was used to identify patients with N0 pancreatic adenocarcinoma who had undergone curative-intent resection between 1988–2003. Kaplan-Meier survival curves were constructed to compare overall survival between patients ± adjuvant radiation therapy. Multivariate Cox regression analysis was performed to determine the prognostic significance of radiation therapy when additional clinicopathologic factors were assessed. The analysis also examined the potential treatment selection bias of patients with survival <3 months. Results: Query of the SEER database identified 2342 surgical patients with N0 disease. The median survival for these patients was 18 months. 889 (60.1%) patients were treated with radiation. There was no difference in gender or grade between radiation and non-radiation groups; however, radiation patients were younger (63 vs. 67 years, p<0.001) and had a greater proportion of T3 lesions (p=0.002). Radiation patients had significantly improved survival compared to non-radiation patients (20.0 vs. 15.0 months, p<0.001). On multivariate analysis, radiation therapy (HR 0.72, p<0.001), age, grade, T-stage, and tumor location were independent predictors of survival. When patients with survival <3 months were excluded from analysis, no difference in survival between radiation and non- radiation was noted (20.0 vs. 19.0 months, p=0.096). However, on subset analysis, patients with T3 tumors demonstrated improved survival with the addition of radiation (24.0 vs 16.0 months, p=0.002) and on multivariate analysis radiation therapy was an independent predictor of improved overall survival (HR 0.87, p=0.027). Conclusions: Radiation treatment is associated with improved survival in operable N0 pancreatic cancer and its use should be considered in patients with early stage N0 disease. The greatest impact of radiation therapy use appears to occur with T3 tumors. No significant financial relationships to disclose.
Detection of circulating tumor cells (CTCs) in patients with hepatocellular carcinoma (HCC)
Authors: Zee B. C. , Wong C. , Kuhn T. , Howard R. , Yeo W. , Koh J. , Hui E. , Chan A. T. 
Published: March 2020

15037 Background: Allard et al. (2004) has established the accuracy, sensitivity, reliability and linearity of circulating tumor cells (CTCs) detection using the CellSearch System. 57% prostate cancers, 37% breast cancers, 37% ovarian cancers, 30% colorectal cancers, and 20% lung cancers specimens had >= 2 CTCs per 7.5 mL of blood. Only 0.3% healthy non-malignant disease subjects had >= 2 CTCs per 7.5 mL of blood. Cristofanilli et al.(2004,2005) have shown that CTCs at baseline and first follow-up were a significant prognostic factor for survival in metastatic breast cancer patients. However, HCC data on CTCs are not available. Methods: 20 locally advance or metastatic HCC patients who had not received prior treatment had been recruited after informed consent and 7.5 mL of blood were collected using the CellSave Preservative tubes (Veridex LLC, Raritan, NJ) that prevents CTCs degradation. The CellSearch system (Veridex LLC) similar to the previous studies was used to analyze the specimen. The CellSearch system consists the CellPrep system, the CellSearch Epithelial Cell Kit, and the CellSpotter Analyzer. All the procedures and interpretation of results followed closely with the quality control procedure of Veridex LLC including accreditation of trained laboratory personnel. Results: 13/20 (65%) had locally advanced disease and the rest had metastatic HCC. All patients had multiple lesions. 9/20 (45%) patients had detectable CTCs, 7/20 (35%) had >= 2 CTCs, and about 5/20 (20%) had 5 or more CTCs. For locally advanced HCC 4/13 (31%) patients had >= 2 CTCs per 7.5 mL of blood. For HCC patients with metastatic diseases 3/7 (43%) patients had >= 2 CTCs per 7.5 mL of blood. Conclusions: HCC patients with locally advance or metastatic disease had detectable CTCs in 7.5 mL of blood. We expected that the performance of CTCs in HCC is similar to that of breast cancer. Future study of using CTCs as prognostic factor at baseline and during treatment for HCC is being planned. No significant financial relationships to disclose.
Magnetic resonance imaging versus mammography for diagnosing ductal carcinoma in situ
Authors: Kuhl C. K. , Schrading S. , Wardelmann E. , Braun M. , Kuhn W. , Schild H. H. 
Published: March 2020

1504 Background: Mammographic screening is considered the mainstay for diagnosing pre-invasive breast cancer (DCIS). However, (over)diagnosis of DCIS has become a major concern. We investigated the sensitivities of high-resolution MRI and of state-of-the-art mammography (Mx) for diagnosing pure DCIS, and compared the biologic profile of MRI-detected versus Mx-detected DCIS. Methods: Prospective study on 5960 consecutive women who were referred to a dedicated breast unit for screening or for diagnostic assessment. Women underwent bilateral mammography with at least 2 views, plus spot compression views where appropriate, and high-resolution bilateral MRI. A total 137 women received the final pathologic diagnosis of having DCIS (no invasion). Of these, 108 (79%) had been referred for regular screening, 14 (10%) for high risk screening, 10 (7%) for follow up after breast cancer, and 5 (4%) for clinical symptoms. We investigated the mode of detection, and the biologic profile of the DCIS (size, nuclear grading, ER/PR and HER2-receptor status). Results: Overall, Mx was positive in 79/137 patients (58%), MRI was positive in 123/137 (90%). In 68/137 (50%), Mx and MRI were concordantly positive. In 3/137 (2%), Mx and MRI were both false-negative. In 11/137 (8%), only Mx was positive, MRI was false- negative. In 55/137 (40%), only MRI was positive, Mx was false negative. Of the 11 DCIS which were only detected by Mx, 1 was high grade, none was ER negative or HER2 positive. Mean VNPI was 4.2. Of the 55 DCIS which were only MRI detected, 41 (78%) were high grade, 14 (27%) were ER negative, 17(33%) HER-2 positive. Mean VNPI was 6.5. Conclusions: Compared to mammography, MRI offers a significantly higher sensitivity for DCIS, in particular for DCIS with adverse biologic profile: Half of the high grade or HER2-positive DCIS were only MRI detected. In turn, DCIS which was only mammography detected had a relatively benign biologic profile. We propose that MRI is helpful for diagnosing biologically (i.e. possibly prognostically) relevant DCIS [Table: see text] No significant financial relationships to disclose.
Preferential inhibition of Sp1 expression in growing tumors by mithramycin-A (MIT) directly correlates with its potent antiangiogenic effects in human carcinoid xenograft model
Authors: Xie K. , Jia Z. , Zhang J. , Wang L. , Li Q. , Le X. , Yao J. C. 
Published: March 2020

15041 Background: MIT, also known as aureolic acid and plicamycin (Mithracin), is an aureolic acid-type polyketide produced by various soil bacteria of the genus Streptomyces. Previous studies have shown that MIT exhibits antitumor activity. In the present study, we examine the antiangiogenic effect of MIT and its underlying mechanisms. Methods: Cohorts of 10 athymic BALB/c nude mice were implanted with 1.5 million human H727 carcinoid cells. Mice were treated with subcutaneous or intraperitoneal 0.2 mg/kg of mithramycin twice weekly once implanted tumor reached 4 mm in size. Results: Both subcutaneous and intraperitoneal MIT significantly suppressed the growth of carcinoid cells in nude mouse models (median tumor weight in PBS, s.c., i.p. groups 790 mm3 vs 280 mm3, 480 mm3; P < 0.01). We also evaluated the Sp1 expression in growing tumors and various organs. We found that the liver expressed the highest level of Sp1 among normal organs (including liver, stomach, large intestine, and small intestine, spleen, kidney, brain and lymph node). However, Sp1 expression in the growing tumors was more than 10 times higher than that in a normal liver. Treatment with MIT reduced the Sp1 expression in the tumors, while no discernible effect on Sp1 expression in normal tissues was observed. This is the first demonstration that MIT selectively inhibited the Sp1 expression in the growing tumors. Consistent with the expression of Sp1, a substantial suppression of VEGF, PDGF, EGFR, and IGFR expression was evident. Finally, treatment with MIT reduced the microvessel formation in tumors by 80% (MVD count; P < 0.01). This antiangiogenic activity was confirmed by in vitro tubulogenesis assay and in vivo Matrigel plug assay. Conclusions: Collectively, our studies strongly indicate that MIT is a potent antiangiogenic agent and its mechanism of action involved suppression of Sp1 expression and its consequent downregulation of its downstream targets including VEGF, PDGF, EGFR, and IGFR that are key to tumor angiogenesis. No significant financial relationships to disclose.