bluuebunny/crossref_metadata_2025_split huggingface dataset:
Favorable genetic polymorphisms predictive of clinical outcome of chemoradiotherapy for stage II/III esophageal squamous cell carcinoma in Japanese
Authors: Okuno T. , Tamura T. , Yamamori M. , Chayahara N. , Miki I. , Shirasaka D. , Nakamura T. , Kasuga M. , Azuma T. , Sakaeda T. 
Published: March 2020

15088 Background: A 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT) was proposed for esophageal cancer patients. Currently, there is an urgent need to establish a methodology to decide which is preferable for a patient, i.e., surgical treatment or CRT, especially for Stage II to III tumors defined as resectable. This study was performed to find the genetic factors predictive of clinical outcome to a 5-FU/ CDDP-based CRT in Japanese patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Thirty-one patients with Stage I-IVa ESCC (I/II/III/IVa = 7/7/14/3) were enrolled in this study. One course of treatment consisted of protracted venous infusions of 5-FU (400 mg/m2/24 h for day 1–5 and 8–12), CDDP (40 mg/m2/3 h on day 1 and 8) and radiation (2 Gy/day on day 1–5, 8–12 and 15–19), and a 2nd course was successively repeated after a 2-week interval. A total of 8 measurements of the plasma concentration of 5-FU were made using high performance liquid chromatography. Genetic polymorphisms examined herein included those in the genes coding thymidylate synthase (TS), glutathione S-transferase P1 (GSTP1) and multi-drug resistant transporter MDR1/P-glycoprotein. Results: The complete response rate depended on Stage (p = 0.001), but the analysis was not sufficiently powered to reach a level of statistical significance for the 2-year survival rate (p = 0.061). For Stage II/III patients, to have 2 or 3 polymorphisms of 3R/3R of 5’-TSER, a 6bp of 3’-TSUTR, and GSTP1-Leu105Val resulted in an extensively longer survival (p =0.0197), although no difference was found between 2 groups, with respect to the plasma concentrations of 5-FU and clinical or pathological characteristics. Conclusions: The genetic prognostic index may allow predictions of the clinical outcome of a 5- FU/CDDP-based CRT in Stage II/III ESCC patients. Now, we are analyzing the contribution of genetic polymorphisms of cytokines, including tumor necrosis factor a. No significant financial relationships to disclose.
Serial ductal lavage for biomarker assessment in a phase 2 prevention study with tamoxifen
Authors: Khan S. , Lankes H. A. , Patil D. , Bryk M. , Nayar R. , Hou N. , Krontiras H. , Rademaker A. 
Published: March 2020

1509 Background: Effective methods of epithelial sampling to measure breast-specific biomarkers will aid the rapid evaluation of new preventive interventions. We report a proof-of-principle Phase 2 study to assess the utility of ductal lavage (DL) to measure biomarkers using tamoxifen (TAM) as the gold standard prevention agent. Methods: We enrolled women with a 5-year Gail risk >1.6 or the unaffected breast of women with breast cancer =1 cm. After entry DL, participants chose TAM or observation (OBS), and underwent repeat DL 6 months later. Samples were processed for cytology and immunohistochemistry for ER and Ki-67 labeling indices (LIs). If =1 duct showed atypia, the sample was called atypical. LI data were analyzed by duct (comparing the same duct at 2 time points) and by woman (comparing the mean of all ducts at 2 time points). Results: Of 168 women recruited, 135 (80%) underwent entry and repeat DL; 82 (49%) had sufficient cells for analysis at both time points (mean age 50 years, mean Gail 3.0). 44 chose observation and 38 chose TAM. Cytologic findings, by woman and by duct, showed significantly greater net improvement (from atypical to benign) in the TAM than in the OBS group (see table ). The repeat ER and Ki-67 LIs showed a significant reduction from entry within the TAM group (p=0.01 and 0.0001, respectively), but not in the OBS group when analysed by duct. Similarly, in analyses by woman, the ER and Ki-67 LIs decreased from entry to repeat DL within the TAM group (p=0.046 and 0.004 respectively), with minimal changes in the observation group. Between-group data are shown in the table and are similar to the within- group differences. Conclusions: Using DL, we saw the expected changes in TAM-related biomarkers, with stronger reductions in duct-to- duct comparisons than when findings were averaged across ducts in individual women. However, the 51% attrition rate of subjects from recruitment to biomarker analyses, along with the expense of DL, raises questions regarding the efficiency of this procedure in biomarker assessment over time. [Table: see text] No significant financial relationships to disclose.
A phase II study of capecitabine-gemcitabine(CapGem) as a first line therapy in Bangladeshi patients with locally advanced or metastatic pancreatic adenocarcinoma
Authors: Reza M. S. , Hai M. A. , Chowdhury Q. 
Published: March 2020

15100 Background: Pancreatic cancer is one of the cancers with very poor prognosis because of its diagnosis at an advanced or metastatic stages. There is no consensus on the optimal management of locally advanced or metastatic pancreatic cancer. This phase II study was designed to evaluate the efficacy and safety of CapGem in patients (Pts.) with pancreatic adenocarcinoma. Methods: From January 2001 to December 2004, 30 pts with; histologically / cytologically proven, bidimensionally measurable locally advanced or metastatic pancreatic adenocarcinoma, age 18∼75 years with ECOG performance status 0∼3, no prior chemotherapy, life expectancy >3 months, adequate bone marrow, renal, hepatic and haematological values were enrolled. It was an open - labeled, non-randomized, single - centered and prospective study. The pts received Capecitabine 750mg/m2 twice dailly,days 1–14,orally and Gemcitabine 1000mg/m2 days 1 & 8, intravenous infusion at an interval of 21 days.The efficacy was measured by response rates, CA-19.9 & pain status and safety was measured by adverse events and laboratory blood values. Results: This study consisted of 16 (53.33%) male and 14 (46.67%) female pts. Median age was 52 years. 18 (60%) pts were inoperable locally advanced and the remaining 12 (40%) were metastatic diseases where 8 hepatic and 4 pulmonary. In total, 152 cycles chemotherapy were administered with a median of 5.06 cycles per pt and 28/30 pts were evaluated for responses. The overall response was 9 ( 32.14%) with 2 complete and 7 partial responses. 14 pts (50%) had stable diseases and 5 (17.86%) had progressive diseases. There was 55% decrease in CA-19.9 and pain reduction was 60%. Overall survival was10 months. Grade 3 haematological toxicities were observed as follows: neutropenia 30% and anaemia 18%. Some non- haematological toxicities including nausea & vomiting 30%, diarrhoea 20% and hand foot syndrome 10% were observed. Conclusions: This phase II study supports the use of CapGem combination in chemo naive locally advanced or metastatic pancreatic adenocarcinoma due to its promising anti-tumor activity with well-tolerated toxicities in Bangladeshi pts. No significant financial relationships to disclose.
Palliative treatment of unresectable pancreatico-biliary cancer by either gemcitabine or octreotide/imatinib: Impact on biomarkers of angiogenesis
Authors: Treiber G. , Wex T. , Malfertheiner P. 
Published: March 2020

15101 Background: Gemcitabine represents standard Tx for unresectable cancers of the pancreas / distal biliary tract. Recent interest has focused on antiangiogenic properties in a mouse model of pancreatic cancer (JCI 2003); either VEGF or PDGF inhibition alone were less effective than the combination of both in terms of angiogenesis. In humans, imatinib (targeting PDGF) alone has been shown to be equivalent to gemcitabine in terms of survival (Cancer Lett. 2006;233:328–37), while most trials for octreotide (targeting IGF-1, VEGF) were disappointing. In HCC pts. we recently evaluated the impact of biomarkers on disease progression and survival (Cancer Res Clin Oncol 2006; 132:699–708). Methods: To investigate in a phase I/II trial the feasability of a combination (group I, n=11) of octreotide (30 mg im every 4 weeks, targeting VEGF-A) plus imatinib (400 mg po daily, targeting PDGF-B) vs gemcitable (group II, n=11, 1000mg/m2 weekly for 7/8 wks, then for 3/4 wks). Pts had either unresectable pancreatic cancer (n=18) or ampullary cancer (n=4). Primary outcome measure were changes in biomarkers (VEGF-A, PDGF-BB, soluble E-selectin, Ca19–9, CEA). Secondary outcome measures were TTP and OS. Results: 19/22 pts. had biomarker data available within the first 12 wks, changes over time are shwon in table . Median TTP was 109 vs 166 days (p<0.05) and median OS was 163 vs 325 days (p=NS) for group I vs II. Baseline Ca19–9 levels correlated with prognosis independent of Tx (p=0.05). In group I, high levels of PDGF-BB and VEGF-A levels at wk 12 but in group II, low levels of VEGF-A and s-E-selectin correlated with a better OS (p<0.05 each). TTP showed no correlations with biomarkers. Conclusions: The combination of octreotide plus imatinib is clinically less effective compared to gemcitabine. Although the absolute changes of angiogenesis markers are comparable between groups, chemotherapy compared to targeted therapy has a different impact on these in terms of survival. [Table: see text] No significant financial relationships to disclose.
Can 1H-Nuclear magnetic resonance (NMR) be used for early detection of hepatocellular cancer (HCC)?
Authors: Iyer R. V. , Tennant B. , Ruiz M. , Szyperski T. , Trump D. , Odunsi K. , Wollman R. 
Published: March 2020

15107 Background: HCC is a common and rapidly fatal cancer. Current screening tools are inadequate for identification of potentially curable cases. Our aim was to determine whether H-NMR can identify HCC compared to controls in the woodchuck (WC) model of hepatitis related HCC. Methods: Eastern WCs were bred and inoculated at birth with dilute sera from WCs that are chronic carriers of Woodchuck Hepatitis B Virus (WHV). This resulted in chronic hepatitis in ∼60% animals and all carriers developed HCC by 24–36 months. Serum from 10 chronic WHV carriers with HCC (group 1), 5 WHV carriers with no HCC (group 2) and 15 matched non-infected controls (group 3) was obtained. 45uL serum was diluted with 5uL of D2O containing 27mM formic acid + 0.9% saline. Spectra were collected on a 600 MHz INOVA spectrometer using a CapNMR flow probe with 10uL flow cell at 298K without knowledge of group assignments. The resulting 1D spectra were processed using Nuts from AcornNMR. Results: Principle component analysis and supervised PLS-DA was performed using Simca P+ from Umetrics. Despite general separation of groups, the Q2 value of this model was relatively low (0.20). We trained a Support Vector Machine (SVM) algorithm, a supervised machine-learning algorithm, to learn to identify the groups. Evaluation of the performance of the algorithm using 10-fold validation on the data set achieved a Kappa value of 0.43. This algorithm learnt to identify HCC [0.765 ROC, 0.8 sensitivity, and 0.727 positive predictive value (PPV)] and controls (0.75 ROC, 0.69 sensitivity and 0.73 PPV) but not the WHV carrier group, likely due to the small numbers. In a second analysis of 10 HCC and 15 controls, PLS-DA showed clear separation using three components (Q2= 0.5). The corresponding SVM model showed a kappa value of 0.52 and ROC values of 0.767 for both classes. Conclusions: Our preliminary results indicate that H-NMR spectra alone can be used to distinguish HCC from healthy controls using the machine-learning algorithm for classification. Further validation in a larger cohort of woodchucks is ongoing and confirmation of these preliminary findings would support investigation of this technique as a screening tool in patients at risk for developing HCC. No significant financial relationships to disclose.
Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer
Authors: Park Y. , Yi S. , Kim H. , Lee S. , Hwang I. , Park S. , Park B. , Park J. , Lim H. , Kang W. 
Published: March 2020

15111 Background: The aim of this phase II study was to determine whether second line therapy with single agent irinotecan could provide any clinical benefit in patients with gemcitabine- pretreated advanced pancreatic cancer. Methods: From January 2004 to October 2006, patients with advanced pancreatic cancer previously treated with gemcitabine alone or combination were treated with single agent irinotecan(150 mg/m2, biweekly), until unacceptable toxicity or disease progression. Primary endpoint was response rate with single stage design. Results: Twenty-eight patients were enrolled(22 male, 6 female, median age : 54.5 years (39–76)). Nine patients are still alive and 3 remain on therapy with stable disease. The median number of cycles was 3.5(1–12). Twenty-four patients were assessable for toxicity and 21 for response. The most common toxicities was diarrhea (grade 3, 12.5%). Grade 3 neutropenia in 1 patient was observed. Other hematological and non-hematological toxicities were mild and manageable. Partial responses were observed in 3 patients (3/21, 14%). An additional 9 patients (9/21, 43%) had stable disease as their best response. 12 patients have progressed with a median time-to-progression of 4.0 months. Conclusions: Single-agent irinotecan was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced pancreatic cancer, refractory to gemcitabine. No significant financial relationships to disclose.
Efficacy of recent chemotherapy regimen in advanced small bowel carcinoma
Authors: Aparicio T. , Costes L. , Moulin V. , Locher C. , Bidault A. , Lecomte T. , Mitry E. , Taieb J. , Landi B. , Malka D. 
Published: March 2020

15112 Background: Small bowel carcinoma (SBC) is a rare tumour. Very few data concerning the chemotherapy efficacy are published. The overall survivals previously reported were 8 to 14 months. The aim of the study was to evaluate the efficacy of recent chemotherapy regimen in advanced SBC. Methods: All the consecutive patients treated recently by first line chemotherapy for advanced SBC were included retrospectively in a multicentric study. Clinical and radiological evaluations were performed every 2 or 3 months according to WHO criteria. Chemotherapy was stopped in case of progression, severe toxicity or patient willing. Results: Fifty seven patients (33 men, 24 women), median age 56 years [32–83] treated from 1994 to 2006 in 10 institutions were included. Primary tumours were: duodenum n=35 (61%), jejunum n=14 (25%) and ileum n=8 (14%). Three patients had Crohn disease and one HNPCC syndrome. The tumour were locally advanced in 6 patients (10%), or with metastasis in 51 (90%), synchronous n=35 or metachronous n=16. The mains metastasis sites were peritoneal carcinomatosis in 29, liver in 19 and nodes in 13 patients. Sixteen patients have had an initial R0 surgery and 8 had received, before inclusion, adjuvant chemotherapy. The regimens used in first line were: FOLFOX n=21 (37%), LV5FU2-cisplatine n=13 (23%), LV5FU2 n=12 (21%), FOLFIRI n=10 (17%). Twenty five (44%) patients have had grade 3 or 4 toxicity. A toxic death occurred after a cure of FOLFOX. Chemotherapy was stopped in relation to toxicity in 7 (12%) patients. A dose reduction was done in 15 (26%) patients for a total of 16% of the cures. Tumor was measurable in 42 (73%) pts. A partial response was observed in 13 patients (31%), stabilisation in 14 (33%) and progression in 15 (36%). Thirty six (63%) pts had a second line chemotherapy. Time to treatment failure was 6 [1–21] months in all patients and 7 [2–19], 7 [2–20], 5 [1–21] and 4 [1–10] months according to treatment by FOLFOX, LV5FU2, FOLFIRI or LV5FU2-cisplatine respectively. Overall survival was 11 months [1–36]. Overall survival according to the primary localization were: duodenum: 9 [1–34], jejunum: 18 [3–32], ileum: 15 [4- 36]. Conclusions: Advanced SBC have a bad prognosis. The chemotherapy regimen used in colon cancer did not reach the same efficacy in SBC. No significant financial relationships to disclose.
Doubling time of preoperative serum alpha-fetoprotein level can predict recurrence and prognosis after hepatic resection of hepatocellular carcinoma
Authors: Masuda T. , Beppu T. , Ishiko T. , Mizumoto T. , Hayashi H. , Horrart H. , Takamori H. , Kanemitsu K. , Hirota M. , Baba H. 
Published: March 2020

15118 Background: It is quite important to predict postoperative recurrence or prognosis in the patients with hepatocellular carcinoma (HCC) before surgery. There have been few reports about the value of doubling time of preoperative serum a-fetoprotein (AFP) or protein induced by vitamin K absence (PIVKA-II) levels. Methods: Between January 2000 to December 2005, 160 consecutive HCC patients underwent hepatic resections in our institution. Serum AFP and PIVKA-II level was prospectively measured at least two points before surgery to calculate a doubling time. Clinical factors such as age, gender, BMI, etiology of hepatitis, degree of liver damage, gross tumor type, tumor size, tumor numbers, portal vein tumor thrombosis (PVTT), and AFP-L3 were concurrently investigated. Univariate and multivariate analyses were done to clarify predictive factors of postoperative recurrence and survival. Results: There were no relationship between preoperative levels and doubling time of both tumor markers. In univariate analysis, significant predictors of postoperative recurrence were AFP > 200 ng / ml, PIVKA-II > 200 mAU / ml, AFP-L3 > 10%, non-simple nodular type tumor, tumor size > 3 cm, multiple tumors, PVTT positive, and doubling time of AFP < 40 days. The significant prognostic factors were AFP > 200 ng / ml, HBs antigen positive, non-simple nodular type tumor, multiple tumors, PVTT positive, and doubling time of AFP < 40 days. In multivariate analysis, multiple tumors (odds ratio: 1.48), and doubling time of AFP < 40 days (odds ratio: 2.17) were significant predictors of recurrence. The significant prognostic factors were non-simple nodular type tumor (odds ratio: 6.41), multiple tumors (odds ratio: 7.62), and doubling time of AFP < 40 days (odds ratio: 6.49). Postoperative mean recurrence free survival time of HCC patients with doubling time of AFP < 40 days was only 2.8 months and mean survival time was 34 months. Conclusions: In HCC patients, doubling time of preoperative serum AFP level is useful to predict early recurrence and poor prognosis. Perioperative adjuvant therapy should be considered for such high risk patients. No significant financial relationships to disclose.
Ki67 labelling index and performance status are predictive factors of response to concomitant radiochemotherapy (RCT) in esophageal cancer
Authors: Seitz J. F. , Dahan L. , Ressiot E. , Liprandi A. , Giorgi R. , D’journo X. B. , Padovani L. , Alibert S. , Ries P. , Thomas P. A. 
Published: March 2020

15119 Background: In oesophageal cancer, preoperative RCT allows a prolonged survival for patients achieving a complete pathological response at time of surgery. However, predictive factors for complete response to RCT are not well known. The aim of this retrospective study was to identify clinical and histopathological factors predictive of complete endoscopic response (CER) in patients treated by RCT before surgery or as exclusive treatment for esophagus cancer. Methods: from 2000 september to 2006 march, 56 patients with esophagus cancer (35 squamous cell carcinoma (SCC), 20 adenocarcinoma (ADK), 1 undifferentiated) were treated by RCT (45–50 grays /25 fractions / 5 weeks and 2 courses of 5FU-CDDP at weeks 1 and 5). 16 patients subsequently underwent oesophageal resection. Endoscopy with biopsies was performed 3 weeks after the end of RCT. Clinical, biological, radiological and pathological (including EGFR, p53 and Ki67 immunostaining) parameters were included in univariate and multivariate analysis to determine predictive factors for CER. Results: CER was observed in 31 out of 54 appraisable patients (57.4%). In both univariate and multivariate analysis, 2 factors were predictive of complete endoscopic response: good performance status (PS 0 vs 1–2: OR = 15.75 - p=0.01) and higher expression of Ki67 (>=18 vs <18: OR = 4.46 - p=0.04).A pCR was seen in 7 (44%) of the 16 operated patients. Positive predictive value of endoscopy for pCR was 87.5% (IC95%: 47.4–99.7%), and negative predictive value was 100% (IC95%: 68.7–100%). Predictive factors of pCR were: a complete endoscopic response (p<0.01), a complete CT-scan response (p=0.03) and a good performance status (p=0.04). Median survival in all 56 patients was 40 months. Pejorative prognostic variables for survival in multivariate analysis were adenocarcinoma histology (RR=3.11; p=0.03), and performance status (RR=4.79; p=0.04). Conclusions: In our study, a good performance status and surexpression of Ki67 were independent predictive factors for complete endoscopic response after RCT. The 2 prognostic factors for survival are histologic type and performance status. No significant financial relationships to disclose.
Phase II study of induction chemotherapy with fixed dose rate (FDR) gemcitabine and cisplatin followed by concurrent chemoradiation with capecitabine for locally advanced pancreatic cancer (LAPC)
Authors: Kim J. , Im S. , Park H. , Chie E. , Hwang J. , Kim J. , Kim T. , Bang Y. , Ha S. , Yoon Y. 
Published: March 2020

15122 Background: Despite the use of 5-FU based chemoradiotherapy (CRT) over the past decades, prognosis of patients with LAPC remains dismal. To deliver more efficient systemic treatment earlier and reduce toxicity of CRT, we designed a treatment protocol consisting of induction (IND) chemotherapy with FDR gemcitabine (GEM) and cisplatin (CDDP), followed by CRT with capecitabine (CAP) in LAPC. Methods: Eligible patients had unresectable, histologically confirmed adenocarcinoma of pancreas, ECOG PS of 0–2, and no prior chemo- or radiotherapy for this phase II study. Patients received FDR GEM 1000 mg/m2 (D1,8) and CDDP 60 mg/m2 (D1) every 3 weeks for 3 cycles. Patients without disease progression subsequently received CRT of 55.8 Gy in 31 fractions concurrently with CAP, 650 mg/m2 given twice daily without drug holidays. Four weeks after CRT, FDR GEM 1000 mg/m2 was given on day 1, 8 every 3 weeks for 3 cycles. Time to progression was the primary endpoint. Results: Between Jan 2005 and Nov 2006, 21 patients were enrolled (median age 59, M/F: 13/8, ECOG PS 0/1: 3/18). Two patients withdrew consent after 1st and 2nd cycle and remaining 19 patients completed all three cycles of IND chemotherapy, with three (15.8%) out of 19 evaluable patients achieving partial response (0 CR, 3 PR, 14 SD, 2 PD). All 17 patients completed CRT with mean radiation dose of 55.4 Gy. Further four patients progressed during CRT, while one additional patient achieved partial response. As of Jan 2007, 5 patients died and 12 patients showed tumor progression. Median TTP was 12.5 mo (95% CI: 4.2–20.8) and median survival was not reached with median follow up duration of 9.7 months. Grade III/IV toxicities included neutropenia (38.1%/9.5%), thrombocytopenia (4.8%/0%), and anemia (14.3%/0%) during IND phase. Toxicites were generally mild during CRT phase with grade III neutropenia and diarrhea occurring in one and two patients, respectively. One patient died of neutropenic sepsis after 3rd cycle of IND chemotherapy. Conclusions: FDR GEM-CDDP induction chemotherapy followed by CAP-RT and maintenance FDR GEM is feasible and active with promising TTP of 12.5 months. Enrollment continues till reaching target accrual of 37 patients. No significant financial relationships to disclose.