bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized phase III trial to determine the efficacy of postoperative antimicrobial prophylaxis in gastric cancer surgery (OGSG0501)
Authors: Inoue K. , Imamura H. , Kimura Y. , Fujitani K. , Miyake Y. , Matuyama J. , Tatsumi M. , Shimokawa T. , Kurokawa Y. , Furukawa H. 
Published: August 2020

e15576 Background: In Japan, antimicrobial prophylaxis (AMP) is typically administered for 3 to 4 days postoperatively in gastric cancer surgery. This far exceeds the recommended 24h or less laid out by the Centers for Disease Control (CDC) guidelines for the prevention of surgical-site infections, after a clean-contaminated operation. Methods: A multicenter randomized phase III trial was designed to evaluate the effect of postoperative AMP in gastric cancer surgery. Patients (pts) were required to have histologically proven gastric cancer which was curable by distal gastrectomy, be classifiable as ASA 1 or 2, and have adequate organ function. Pts were randomized to: (A) perioperative AMP (cefazolin 1g, at <30min before incision, every 3h intraoperative supplements) plus postoperative AMP (cefazolin 1g, twice daily for 2 postoperative days) or (B) perioperative AMP alone. Pts were stratified by institution and ASA. The primary endpoint was the incidence of surgical site infection (SSI). With 171 pts per arm, this study had 80% power to demonstrate non-inferiority with 5% margin of peri-AMP alone and 0.05 1-sided alpha. Results: 355 patients were recruited (A: 179, B: 176) in 7 centers between June 2005 and December 2007. The surgical-site infection rate was 9.0 percent (16 of 178) for peri-/post AMP and 4.5 percent (8 of 176) for peri-AMP alone, with no significant differences (Fisher's exact test: P=0.14, RR=1.98 [95%CI, 0.89–4.44]), but showing a significant non-inferiority (P<0.001). The remote site infection rate was 3.4 percent (6 of 178) for peri-/post AMP and 5.1 percent (9 of 175) for peri-AMP alone, with no significant differences (P=0.44, RR=0.66 [95%CI, 0.25- 1.70]). Conclusions: This multicenter randomized phase III trial confirms that postoperative AMP is unnecessary in patients undergoing distal gastrectomy for gastric cancer. No significant financial relationships to disclose.
Phase II study of gemcitabine chemotherapy alone for locally advanced pancreatic carcinoma: JCOG 0506
Authors: Ishii H. , Furuse J. , Boku N. , Okusaka T. , Ikeda M. , Ohkawa S. , Fukutomi A. , Hamamoto Y. , Nakamura K. , Fukuda H. 
Published: August 2020

e15578 Background: Fluorouracil (5-FU) chemoradiotherapy has been accepted as standard care for locally advanced pancreatic cancer (LAPC); however, it has not been shown to be superior to chemotherapy alone in gemcitabine (Gem) era. The present multicenter phase II study was conducted to evaluate the efficacy and the safety for the screening of Gem monotherapy against LAPC. Methods: Eligibility criteria included the following: patients (pts) with histologically or cytologically proven pancreatic adenocarcinoma or adenosquamous carcinoma, pts with UICC clinical stage III (T4N0–1 and M0), all lesions are assumed to be included in the radiation field of 15 cm square, age 20 or older, no prior treatment for LAPC, ECOG performance status of 0, 1 or 2, and adequate organ function. Gem was given intravenously at a dose of 1,000 mg/m2 over 30 minutes on days 1, 8 and 15, repeated every 4 weeks until disease progression. The primary endpoint was %1-year overall survival. A sample size of 50 was required with one-sided alpha of 0.20, beta of 0.10, expected %1-year survival of 40% and threshold %1-year survival of 25%. Results: Between Jan. 06 and Feb. 07, 50 pts from 14 institutions were registered. Patient characteristics were: median age; 67.5 (45–80), male/female; 35/15, PS 0/1/2; 30/20/0, pancreatic head/body-tail; 26/24. The major grade 3–4 adverse events were neutropenia (62%), leucopenia (32%), thrombocytopenia (18%), fatigue (12%), infection-biliary tree (10%), anorexia (8%), and nausea (6%). Hematological toxicity was mostly transient and there was no episode of infection with grade 3–4 neutropenia. There were no treatment-related deaths during the study. Serum CA 19–9 level was reduced by >50% in 37.5% of 40 pts with baseline CA19–9 >100U/ml. Up to the final follow-up in Apr. 08, the median overall survival was 1.25 years (95% CI, 1.06–1.71 years) with a %1-year survival of 64.8% (95% CI, 49.6–76.4%), and the null hypothesis (%1-y survival=25%) was rejected (p<0.0001). Conclusions: Gem monotherapy demonstrated far better survival than historical data of 5-FU chemoradiotherapy in LAPC pts with mild toxicities. In future randomized trial, we will select Gem chemotherapy as a referential arm to compare with the chemoradiotherapy regimen which is under phase II evaluation for LAPC. No significant financial relationships to disclose.
Sorafenib in hepatocellular carcinoma (HCC) patients after liver transplantation
Authors: Feun L. G. , Levi D. , Moon J. , Nishida S. , Island E. , Selvaggi G. , Martin P. , Savaraj N. , Mendes F. , Tzakis A. 
Published: August 2020

e15579 Background: Sorafenib has been approved for the treatment of advanced HCC. However, there is no data on its use for HCC patients (pts) after liver transplantation (OLT). Pts at high risk for tumor recurrence (native liver showing vascular invasion, multiple tumors >3 in number, size >6 cm, or lymph node involved) after OLT or who develop recurrence after OLT have worse prognosis. These pts may potentially benefit from sorafenib. Methods: We reviewed our experience with HCC pts after OLT treated with sorafenib. 15 pts had a starting dose of 400 mg po bid and 3 had a starting dose of 200 po bid. Sorafenib was started 3 months (mo) after OLT as adjuvant therapy (7 pts) or at the time of tumor recurrence after OLT (11 pts). CT or MRI scans of the chest/abdomen and physical exams were performed every 2–3 mo. Lab tests including serum AFP were performed monthly. Results: Median age was 60 (range 53–75). Median performance status was 90%(range 80–100). In terms of toxicity, 4 of the 15(27%) pts on the initial dose of 400 mg bid stopped sorafenib due to unacceptable toxicity and 5 (33%) had dose reduction due to toxicity. Grade 3/4 toxicity included skin rash, fatigue and anorexia, hyperbilirubinemia, chest/abdominal pain. Only 40% could continue at the full recommended starting dose of sorafenib.For the 11 pts with recurrent disease after OLT treated with sorafenib, the sites of evaluable disease include liver (5 pts), lung (3), others (3). One pt (9%) had a partial response in lung metastases for 10 mo. and the median time to tumor progression (TTP) was 4 mo. (range 2–10 mo). For pts on adjuvant sorafenib after OLT, no pt has relapsed so far with a median followup of 6+ mo. (range 2+ to 15+ mo). Conclusions: The response rate and TTP for pts treated with sorafenib for recurrent HCC after OLT is similar to HCC pts without OLT (Llovet, NEJM 2008). Since the majority of HCC pts after OLT treated with sorafenib required either dose reduction or stoppage due to toxicity which is higher than previously reported, a lower starting dose with dose escalation may be preferred. Contributing factors for toxicity may include the anti-rejection drugs (tacrolimus, mycophenolate, steroids) used for OLT which might affect pharmacokinetics(PK) of sorafenib. Further PK studies with sorafenib in HCC pts after OLT for future clinical trials are indicated. No significant financial relationships to disclose.
Fixed dose rate infusion of gemcitabine and UFT combination chemotherapy in patients with advanced biliary cancer
Authors: Lee S. , Ryoo H. , Bae S. , Song H. , Kim M. , Lee K. , Lee W. , Park K. , Kim J. , Baek J. 
Published: August 2020

e15581 Background: Biliary cancer is diagnosed at advanced stage and recurrence is common after surgical resection. Gemcitabine and UFT combination chemotherapy showed promising results in advanced pancreatic cancer(APC) and fixed dose- rate(FDR) infusion(10mg/m2/min) of gemcitabine is more effective than 30min-infusion in APC patients. We conducted a prospective multicenter phase II study to evaluate the efficacy and toxicity of FDR gemcitabine and UFT combination chemotherapy in advanced biliary cancer(ABC) patients. We evaluated the quality of life(QOL) and relationship between treatment outcome and polymorphisms of DNA repair gene such as RecQ1, RAD54L, XRCC1 and ATM. Methods: We included the chemo-naive patients with measurable metastatic or recurrent biliary adenocarcinoma except gall bladder cancer. Patients received gemcitabine infusion of rate of 10mg/m2/min on day 1, 8, and 15 plus oral UFT (400mg/m2) on day 1 to 21. We used modified PCR-RFLP method to evaluate the polymorphism of DNA repair gene. The primary endpoint was response rate. Results: From October 2006 to March 2008, 47 patients were enrolled and 33 of them were included in this analysis. Median age was 58 years(range 33–73 years) and 18 patients were male. Partial response was 24.2% and disease control rate was 51.5%. The estimated median time to progression(TTP) was 87 days(95% CI 51–123). Median overall survival was 243 days(95% CI 114–372). Grade 3/4 neutropenia was observed in 12 of 33 patients(36.4%) and 17 times of 114 cycles of chemotherapy(14.9%). No febrile neutropenia was observed. Grade 3/4 thrombocytopenia occurred in 5 patients(15.2%). Non-hematologic toxicities were mild. Polymorphism of XRCC1 was related to TTP(TTP of wild, heterozygous variant and homozygous variant type was 162, 71 and 25 days, respectively. p=0.0039). QOL as a secondary endpoint was not analyzed at this time. Conclusions: FDR infusion of gemcitabine and UFT combination chemotherapy in chemo-naïve patients with ABC is a well-tolerated and effective regimen. No significant financial relationships to disclose.
Discovery of a tumor-specific biomarker for gastric cancer using proteomic analysis in tissue and serum
Authors: Mohri T. , Mohri Y. , Ward D. G. , Wei W. , Qi Y. , Martin A. , Kusunoki M. , Johnson P. J. 
Published: August 2020

e15582 Background: Gastric cancer is curable at an early stage. However, most cases are diagnosed at an advanced stage because of the lack of screening programs. Therefore, for early detection, there is a need for serum biomarkers to be identified. Methods: We explored surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to elucidate potential protein biomarkers of gastric cancer. Twenty-one resected gastric cancer samples were compared with matched adjacent normal mucosa samples. Serum from patients with gastric cancer (n=51) was compared with patients with benign gastric diseases (n=29). Samples were analyzed on Cu2+-loaded IMAC protein chips via surface-enhanced laser desorption /ionization time-of-flight mass spectrometry. Results: Comparisons of surface-enhanced laser desorption /ionization time-of-flight mass spectrometry spectra of 21 gastric cancer tissue extracts with paired adjacent normal mucosa showed a total of 56 differentially expressed protein peaks (p<0.05; Wilcoxon test). Twenty-two were up-regulated in gastric cancer tissue, whereas 34 were down-regulated. The surface- enhanced laser desorption /ionization time-of-flight mass spectrometry spectra of serum contained 130 peaks, of which 67 were significantly associated with gastric cancer (p<0.05; Wilcoxon test). We found five proteomic features (mass charge values of 2273, 3143, 3372, 3444, 3485) that were significantly up-regulated in both gastric cancer tissue and serum from gastric cancer patients. The peak intensities of tumor-specific proteomic features were used to develop a linear regression model for calculating a diagnostic index. The area under the receiver operating characteristic curve of the corresponding diagnostic index was 0.87. Conclusions: Serum biomarker panels associated with tumor tissue are capable of distinguishing gastric cancer patients from non-cancer ones. No significant financial relationships to disclose.
Control of cancer-associated inflammation and survival: Results from a prospective randomized phase II trial in gastric cancer
Authors: Reichle A. , Lugner A. , Ott C. , Klebl F. , Vogelhuber M. , Berand A. , Andreesen R. 
Published: August 2020

e15584 Background: An angiostatic approach was used to assess the impact of anti-inflammatory therapy in combination with metronomic low-dose chemotherapy. Methods: A randomized multi-institutional phase II trial was designed to select metronomic chemotherapy (arm A: capecitabine 1 g orally twice daily for 14 days with one week break until tumor progression) or combined anti-inflammatory/angiostatic treatment (arm B: capecitabine as mentioned above plus etoricoxib 60 mg orally, day 1+, and pioglitazone 60 mg orally, day 1+) for further evaluation. Patients with refractory or progressive disease following any first-line therapy except capecitabine or frail were eligible. According to the one stage design, a sample size of 64 patients was calculated for the primary objective, improvement of response rate. Results: As similar response rates were observed (arm A/B 15/14%) after the accrual of 42 patients, the study was closed (n=20 (A), n=22 (B); median age 69 years (range 46 to 86ys); frail A/B n=9/11). Median progression- free survival for arm A/B was 3.0/2.9 months (P=0.878), and overall survival 5.0/6.1 months (P=0.778). In both treatment arms a significant decline of serum C-reactive protein (CRP) levels was observed within the first 4 to 6 weeks on treatment, A/B P= 0.01/0.04, respectively. CRP response > 50% from baseline was associated with a significantly improved overall survival in arm A/B (3.1 versus 11.0 months, P= 0.023/ 3.3 versus 7.1 months, P= 0.078) indicating an impact of inflammation-control on survival. WHO grade 3 (no grade 4) toxicities were reported in arm A/B in 20% and 23%, respectively, mostly due to hand-foot-syndrome. Conclusions: Metronomic low- dose chemotherapy in gastric cancer may induce anti-inflammatory response, but the chosen additional anti-inflammatory approach neither has impact on tumor-associated inflammation nor on response or survival rate. In a historical comparison, CRP-responder have similar outcome as patients treated with combination chemotherapy in first-line. No significant financial relationships to disclose.
Repeated transarterial chemoperfusion and -embolization (TACE) in primary hepatic cholangiocarcinoma (CCC): Local tumor control and survival rate
Authors: Vogl T. J. , Naguib N. , Zangos S. , Eichler K. , Gruber T. 
Published: August 2020

e15595 Background: To evaluate local tumor control and survival data in the palliative and symptomatic treatment of hepatic cholangiocarcinoma (CCC) using repeated transarterial chemoperfusion and -embolization (TACE) with two different chemotherapy protocols. Methods: 41 patients with primary cholangiocarcinoma (CCC) were repeatedly treated with transarterial chemoembolization (TACE) in 4-week intervals. In total, 291 TACE sessions were performed with a mean of 7.1 sessions per patient (mean age: 57.1 years; range, 37–80 years). 22 patients had multiple tumors, 6 showed 1 lesion, 5 had 2 lesions and 8 presented 3 to 4 lesions. The local chemotherapy protocol consisted of Mitomycin C alone (n=20), or in combination with gemcitabine (n=18). Embolization was performed with lipiodol and starch microspheres for vessel occlusion. Tumor response was evaluated by magnetic resonance imaging (MRI) in 3-month intervals. Results: Evaluation of local tumor control according to the RECIST criteria was as follows: partial response 9.8%, stable disease 43.6%, and progressive disease 46.6%. The 1-year survival rate after TACE was 58%, the 2-year survival rate was 21%. The mean survival time from the date of diagnosis of liver involvement was 34.1 months (according to Kaplan-Meier), after first TACE treatment 16.7 months. The median survival time of the palliative group was 14.5 months and of the symptomatic group 6 months. Conclusions: Our data indicated that repeated TACE using the protocols is well tolerated and yields respectable results in patients with unresectable liver lesions from CCC. No significant financial relationships to disclose.
Hedgehog signaling: Gli2 and its influence in squamous esophageal cancer
Authors: Manickavasagam K. , Servarayan C. M. , Rao S. , Chandramohan A. 
Published: August 2020

e15596 Background: Gli family zinc finger proteins are mediators of Sonic hedgehog (Shh) signaling and are implicated as potent oncogenes. Gli2 plays a dual role as activator of keratinocyte proliferation and repressor of epidermal differentiation. This study is to determine the expression pattern and the extent of Hh-signaling molecule(Gli2) in squamous cell carcinoma of oesophagus. Methods: A prospective immunohistochemical experimental study was done to identify the expression of Gli2 in 64 cases of squamous cell carcinoma of oesophagus. The study population consisted of patients of the age group 38–87 yrs. The cases consisted of 29 cases of keratinised squamous cell carcinoma.. Of the 64 cases, 20 were well differentiated, 9 moderately differentiated and 35 poorly differentiated tumours. Results: See Table . Gli2 expression was 25%. The cytoplasmic expression is positive in 9 cases and nuclear expression is positive in 5 cases. The average intensity of cytoplasmic expression was more than that of nuclear expression.Gli2 is less expressed in elderly cancers.Gli2 expression is comparatively more in upper third tumours. There were no obvious differences amongst the sex, differentiation and keratinization. The reason can be attributed to the fact that Hh signalling pathway works in a time, concentration and position dependent manner.Conclusions: Deregulation of Hh signalling will result in defective proliferation and differentiation of cells. These findings can be used for better prognosis of the patients by using stem cell therapy and HH pathway inhibitors in the treatment for squamous cell carcinomas of oesophagus. Protein kinase A (Pka) maintains the Gli transcription factors in an inactive state, so activation of Pka with agonists such as forskolin would prevent Gli-mediated activation of target-gene transcription. Gli can also be inhibited at the RNA level by targeting its transcripts with antisense oligonucleotides. To the best of our knowledge, this is the first study of expression of Gli2 in squamous cell carcinoma of oesophagus. [Table: see text] No significant financial relationships to disclose.
Early predictive value of 18F-FDG-PET assessment in advanced esophagogastric junction and gastric cancer patients treated with cetuximab-containing therapy
Authors: Di Fabio F. , Pinto C. , Rojas Llimpe F. , Castellucci P. , Fanti S. , Mutri V. , Giaquinta S. , Di Tullio P. , Pini S. , Compagnone G. , Martoni A. 
Published: August 2020

e15601 Background: 18F-FDG-PET/CT (PET) was reported to predict the pathological response during preoperative chemotherapy in esophagogastric junction (GEJ) or gastric (G) cancer pts. The aim of this study is to evaluate the usefulness of an early change in PET at several time-points in predicting response to cetuximab-containing therapy in pts with advanced GEJ or G cancer. Methods: We evaluated 51 pts with locally advanced/metastatic GEJ or G adenocarcinoma who underwent a first line cetuximab- treatment in two Italian phase II studies. Twenty nine pts (GEJ/G = 5/24; locally advanced/metastatic = 2/27) received cetuximab in combination with cisplatin/docetaxel (DOCETUX study) and 22 pts (GEJ/G = 2/20; locally advanced/metastatic = 3/19) received cetuximab in combination with FOLFIRI (FOLCETUX Study). PET scans were performed at baseline, and in FDG-avid pts, again on day 21 in the DOCETUX study and on day 42 in the FOLCETUX study. Metabolic response was defined as a decrease in maximum standard uptake value (SUV) ≥35% on the basis of our previous study (Di Fabio et al., Gastric Cancer 10:221–227, 2007).Objective response, according to RECIST criteria, was assessed by CT scan at baseline and every 6 weeks. Results: Five pts (10.2%) had FDG non- avid tumor (all pts with signet cell carcinoma). In the 46 FDG-avid tumor pts, the median SUV at baseline was 10.3 (range 5.0 - 36.4). The response rate (RR) was significantly higher in pts with a drop ≥35% in SUV from baseline to day 42: 83% (10/12 pts) in metabolic responders vs. 25% (2/8 pts) in non-metabolic responders (p= 0.019). In contrast, the SUV change at day 21 did not correlate with objective response: RR 57.1% (8/14 pts) in metabolic responders vs. 41.7% (5/12 pts) in non-metabolic responders (p= 0.695). The RR in non-avid tumor pts was 20% (1/5 pts). Conclusions.Our study suggests that in advanced gastric cancer pts with FDG-avid tumor the PET predicts objective response at day 42, but not at day 21. A PET response assessment can provide an opportunity to change the treatment in non-responder pts. Prospective trials defining the role of PET in gastric cancer are warranted. No significant financial relationships to disclose.
Real world treatment patterns of gastrointestinal stromal tumor patients
Authors: Morgan J. A. , Guo A. , Williams D. , Guérin A. , Latremouille-Viau D. , Tsaneva M. , Yu A. P. , Wu E. , Signorovitch J. , Demetri G. D. 
Published: August 2020

e15602 Background: Imatinib is accepted as the standard first-line therapy to treat gastrointestinal stromal tumor (GIST) in patients with unresectable or metastatic disease. In the case of disease progression, physicians may consider increasing imatinib dose or switching to another second-line agent, such as sunitinib. The aim of this study was to analyze the real-world long term treatment patterns of GIST patients. Methods: Two large claims databases from 01/1999 to 03/2008 were combined (MarketScan and Ingenix Impact) to extract patients diagnosed with GIST who initiated on imatinib ≥400 mg/day. Patients were followed from the first observed imatinib prescription to the end of data availability. Patients who dose increased during the study period were defined as dose escalators, while patients who later switched to sunitinib with or without dose escalation were defined as switchers. Kaplan Meier analyses were used to estimate the rate of treatment changes over time including imatinib discontinuation, defined as a lack of imatinib supply for ≥60 days, and switching back to initial treatment. Results: Among the 1,508 GIST patients who initiated on imatinib, 253 patients had a dose increase and 153 patients switched to sunitinib during the study period. 20.1% patients on imatinib discontinued by the end of the first year, and 43.0% discontinued by the end of the third year. Among the 153 switchers, 61 patients had a dose escalation prior to the switch, of which 82.0% reached 800 mg before switching. Among all the switchers, 20.3% switched back to imatinib within 6 months. Conclusions: These claims-based findings on the duration of first-line imatinib therapy of GIST patients supports data on imatinib efficacy in treating GIST from formal clinical research studies. Most of GIST patients who initiated imatinib continued on this therapy without undergoing dose increase or switch to sunitinib. Among switchers, most did not dose escalate before switching and many eventually switched back to imatinib. It appears that physicians tend to not always follow clinical practice guidelines developed based on expert consensus, with respect to decision rules for dose escalation, or for the appropriate time to change kinase inhibitor therapy. [Table: see text]