bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic implication of the maximum standardized uptake value (mSUV) on 18F FDG-PET in patients with metastatic hepatocellular carcinoma
Authors: Shin D. , Han S. , Oh D. , Im S. , Kim T. , Bang Y. 
Published: August 2020

e15531 Background: The role of 18F-fluorodeoxyglucose-positron emission tomography (18F FDG- PET) in hepatocelluar carcinoma (HCC) has not been firmly established. We conduct this study to investigate the value of mSUV on 18F FDG-PET as a prognostic factor in HCC, especially in metastatic setting. Methods: We consecutively enrolled HCC patients with extrahepatic metastatic lesions, who have been evaluated with 18F FDG-PET before palliative anticancer treatment, between January 2000 and June 2008 at the Seoul National University Hospital. We retrospectively analyzed the clinical outcome and the value of mSUV as a prognostic factor. Results: A total of 57 patients (male, 86.0%) were enrolled. Median age was 57 years (range, 36–78). Hepatitis B was the predominant cause of HCC (82.5%), followed by non-viral hepatitis (14.0%) and hepatitis C (3.5%). Most patients (94.7%) were Child-Pugh A and 3 patients (5.3%) were Child-Pugh B. The most commonly involved site was lung (47%), bone (26%), and LN (33%). Median serum AFP level was 68ng/ml (range, 2–48000) and the median mSUV was 4.1 (range, 0.5–57.0). Forty patients (70.2%) received systemic chemotherapy, 14 patients (24.6%) received palliative radiotherapy, 23 patients (40.4%) received palliative surgery, and 7 patients (12.3%) received TACE. In univariate analysis of overall survival (OS), patients with mSUV over 4.0, AFP over 400ng/ml, and presence of intrahepatic viable lesion, and no palliative surgery showed significantly shorter OS (p=0.007, p=0.006, p<0.001, p=0.02, respectively). In multivariate analysis of OS, mSUV over 4.0, AFP over 400ng/ml, and presence of intrahepatic viable lesion were independent prognostic factors (p=0.01, p=0.01, p<0.001, respectively). In patients with mSUV > VS <4.0 or AFP > VS <400ng/ml, there was no difference of palliative anticancer treatment pattern. When combined mSUV with AFP, the OS of patients with mSUV >4.0 and AFP>400ng/ml VS mSUV <4.0 or AFP<400ng/ml VS mSUV <4.0 and AFP<400ng/ml was 11.0 months vs 16.0 months vs 35.7 months, respectively (p=0.006). Conclusions: The mSUV on 18F FDG-PET is a prognostic factor for OS in patients with metastatic HCC. The combined analysis of mSUV with AFP can have a more potent prognostic impact. No significant financial relationships to disclose.
A phase II trial of thalidomide plus tegafur/uracil for patients with advanced/metastatic hepatocellular carcinoma (HCC): Final report
Authors: Hsu C. , Lin Z. , Lee K. , Yeh K. , Hsiao C. , Shen Y. , Chang D. , Wang S. , Hsu C. , Cheng A. 
Published: August 2020

e15533 Background: Thalidomide (T) is an anti-angiogenic agent with modest activity in advanced/metastatic HCC. Tegafur/uracil (UFT) is an oral prodrug of 5-fluorouracil with activity against various gastrointestinal cancers. Metronomic chemotherapy has been shown to have anti-angiogenic and anti-cancer effect in preclinical and clinical models. This study evaluated the efficacy and safety of the combination of T and metronomic UFT as first-line therapy for advanced HCC. Methods: Patients (Pts) with advanced HCC not treatable by surgery or other loco-regional therapies received T 100mg bid and UFT 125mg/m2 (based on tegafur) bid continuously. Treatment was continued in the absence of disease progression or unacceptable toxicity. Primary endpoint was response rate (RR) by RECIST; secondary endpoints were disease control rate (CR+PR+SD), progression-free survival (PFS), overall survival (OS), and safety. Results: Between Jul 2006 and Jul 2008, 43 intent-to-treat pts (M/F 41/2, median age 55) were enrolled. Baseline characteristics were HBsAg(+)/anti-HCV(+)/both(+) /both(-) 31/6/1/7; AJCC stage II/III/IV 2/18/23; BCLC stage B/C 1/42; CLIP score ≤3/4 27/16; portal vein thrombosis 65%; extrahepatic metastasis 58%; prior local treatment 72%. There were 4 PR (9.3%) and 10 SD (23.3%), with a disease control rate of 32.6%. Median OS was 4.6 (95% CI, 3.5–7.3) months and median PFS was 1.9 (95% CI, 1.8–2.6) months. The OS and PFS for pts with CLIP score ≤3 were 7.6 and 2.6 months, respectively. Grade 3 leucopenia developed in 1 (2.3%) pt. The most common treatment-related grade 3 non-hematologic toxicities were somnolence (n=4, 9.3%), GI bleeding (n=3, 7.0%), and elevated transaminase (n=2, 4.7%). No grade 4 toxicities occurred. Conclusions: The combination of T with metronomic UFT is a well-tolerated regimen with moderate activity for advanced HCC, and worth further exploration in pts with CLIP score ≤3. [Table: see text]
Clinical role of regulatory T cell in intraductal papillary mucinous neoplasms
Authors: Morine Y. , Shimada M. , Imura S. , Uchiyama H. , Uchiyama H. , Kanemura H. , Arakawa Y. , Hanaoka J. , Sugimoto K. 
Published: August 2020

e15537 Background: Intraductal papillary mucinous neoplasms of pancreas (IPMNs) have malignant potential and exhibit a broad histologic spectrum, ranging from adenoma to invasive carcinoma. Recently, several investigators have reported that regulatory T cells (Foxp3+CD4+ T cells including CD4+CD25+ T cells and CD4+CD25- T cells) play important roles in anti-tumor immunity. We previously reported clinical role of increased populations of Foxp3+CD4+ T cells (Treg) in peripheral blood from advanced pancreatic cancer patients (Pancreas 2006). This study was conducted to clarify the clinical role of Treg for surveillance of IPMNs. Methods: Thirty-five patients with IPMNs (IPMC: n=8, IPMB: n=2, IPMA: n=5) and pancreas cancer (n=20) who underwent surgical resection were included in this study. Peripheral blood was withdrawn from IPMN patients (IPMC: n=5, IPMA: n=2) and PC patients (n=20), as well as healthy volunteer donors (n=20) as controls. The peripheral blood mononuclear cells (PBMCs) were subjected to FACScan analysis after labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Immunohistochemical expression of Foxp3 (abcam: FOXP3 antibody, 236A/E7), Fascin (Dako: Fascin antibody, 55K-2) and TGF-β (Santa Cruz: TGF-β1 antibody, SC146) in main tumor was assessed in all IPMN patients. Results: The Treg population among the PBMCs was significantly increased in IPMC patients (median: 4.50%) and PC patients (median: 3.06%) compared with healthy donors (median: 1.30%). No significant difference in the Treg population among the PBMCs was observed between IPMC and PC patients. On the other hand, in IPMA patients (n=2), the Treg population among the PBMCs was equivarent to healthy donors (2.40 and 1.85% respectively). In immnohistochemical staining, the positive expression of Foxp3 was 87.5% (7 of 8) in IPMC patients, while in IPMA and IPMB patients, the expression of Foxp3 was not observed. The expression of Fascin and TGF-β was not correlated to malignant potential of IPMNs Conclusions: Increase of Foxp3+CD4+ T cells in the PBMCs is a new promising marker for malignant potential in IPMNs patients. No significant financial relationships to disclose.
Phase I study of SIR-sphere plus sorafenib as first-line treatment in patients with nonresectable hepatocellular carcinoma: The Asia-Pacific Hepatocellular Carcinoma Trials Group protocol 05 (AHCC05)
Authors: Chow P. K. , Poon D. , Choo S. , Lai H. , Goh A. , Lim T. , Lo R. , Tay K. , Tan S. B. , Soo K. 
Published: August 2020

e15538 Background: Sorafenib has been shown to significantly prolong survival in patients with nonresectable hepatocellular carcinoma (HCC) without however significant tumour regression. The addition of radio-ablative therapy could confer additional survival benefit. This phase I trial was carried out to ascertain the toxicities and safety of this combination and was designed as a prelude to a phase II trial. Methods: Eligible patients were administered SIR-sphere (max dose 3 GBq) and subsequently given Sorafenib therapy (400mg bd) either 14 days (Cohort 1: first 3 patients) or 11 days (Cohort 2: subsequent patients) later. Assessment was carried out for 30 days after commencement of Sorafenib. Results: 10 patients were recruited into this phase I trial. The second patient became ineligible for sorafenib therapy after SIR-sphere due to pulmonary bleeding not related to radio-therapy and was excluded from assessment. The characteristics of the patients are in the Table. At the end of the study period, there was no adverse events (AE) of grade 3 or 4 for Cohort 1 and 3 for Cohort 2. The only serious adverse event (SAE) recorded was from Cohort 2. Conclusions: Starting sorafenib 14 days after SIR-sphere therapy is associated fewer AEs and SAEs. The phase II trial has commenced withsorafenib starting 14 days after SIR-sphere. [Table: see text] [Table: see text]
Phase II trial of biweekly reduced-dose combination chemotherapy of oxaliplatin/5-fluorouracil/folic acid (Modified FOLFOX) as first-line chemotherapy in elderly patients with metastatic or recurrent gastric cancer
Authors: Kim H. , Lee B. , Kim T. , Nam S. , Kim B. 
Published: August 2020

e15544 Background: Although combination chemotherapy as ECF (epirubicin, cisplatin, and 5-FU) and DCF (docetaxel, cisplatin, and 5-FU) are effective advanced gastric cancer, but it is too toxic to apply for elderly patients with increased comorbidity. Combination of oxaliplatin and 5-FU has proven to be a effective and tolerable regimen in advanced gastric cancer, and we investigated the efficacy and safety of reduced-dose combination chemotherapy of oxaliplatin/5-FU/folic acid as first-line chemotherapy in elderly patients with metastatic or recurrent gastric cancer. Methods: Elderly patients (≥60 years) with measurable, metastatic or recurrent gastric cancer were enrolled. Patients received oxaliplatin 75mg/m2 (2-hour intravenous infusion on D1), 5-FU 1000mg/m2 (12-hour continuous infusion on D1,2), and folic acid 20mg/m2 (15-minute infusion on D1,2) every 2 weeks. Results: Total 37 patients were enrolled between April 2004 and August 2008. Median age was 67 years old (range, 60 to 80 years), and 22 patients (59.5%) had increased Charlson comorbidity index score (CCI ≥1). Of 36 evaluable patients, 2 patients achieved complete response (CR), and 12 patients partial response (PR) with representing overall response rate of 44.4% (95% CI 27.7- 60.2). Stable disease (SD) was observed in 12 patients (33.3%), and progressive disease in 8 patients (22.3%). The median time to progression was 4.6 months, and median overall survival was 9.2 months. Relative dose intensity was 97.4% in both oxaliplatin and 5-FU. Grade 3 or 4 hematologic toxicities included neutropenia in one patients (2.7%), and anemia in three patients (8.1%). Peripheral neuropathy occurred (grade 2) was only observed in three patients (8.1%). Conclusions: The reduced-dose combination chemotherapy of oxaliplatin/5-FU/folic acid was effective and tolerable in elderly patients with metastatic or recurrent gastric cancer as first-line treatment. No significant financial relationships to disclose.
Phase II study of mFOLFOX-4 followed by mFOLFIRI in advanced gastric cancer
Authors: Kwon H. , Lee S. , Oh S. , Kim S. , Kim H. 
Published: August 2020

e15546 Background: FOLFOX followed by FOLFIRI regimen has been commonly used in colorectal cancer. This combination has also been evaluated in a number of phase II studies in the first- and second-line treatment setting of advanced gastric cancer. We have evaluated the efficacy and toxicity of modified FOLFOX-4 followed by modified FOLFIRI regimens in advanced gastric cancer patients. Methods: Previously untreated patients with advanced or recurrent gastric cancer were enrolled. As first-line therapy, patients received modified FOLFOX-4, bolus ldLV 50mg followed by a 5-FU bolus 400mg/m2 and 22-hour infusion 600mg/m2 on day 1 and 2, with oxaliplatin 85mg/m2 on day 1 every 14 days. At progression, patients received modified FOLFIRI, bolus ldLV 50mg followed by a 5-FU bolus 400mg/m2 and 22-hour infusion 600mg/m2 on day 1 and 2, with irinotecan 150mg/m2 on day 1 every 14 days as second-line therapy. Results: Fifty-six patients were enrolled in first-line mFOLFOX-4. Of these, 32 (57.1%) patients received sequential mFOLFIRI as second-line chemotherapy. In first- line therapy, mFOLFOX-4 achieved 41.4% (95% CI, 28–54%) partial response and 32.1% (95% CI, 20–45%) stable disease. The median time to progression was 4.2 months (95% CI, 2.8–5.5 months). In second-line therapy, mFOLFIRI achieved 18.8% (95% CI, 4–33%) partial response and 31.3% (95% CI, 14–48%) stable disease. The median time to progression was 3.1 months (95% CI, 1.4–4.7 months). Median survival was 12.8 months (95% CI, 9.5–16.0 months) in overall 56 patients, and median survival of sequential chemotherapy was 13.2 months (95% CI, 9.4–16.9 months) in 32 patients. In first-line mFOLFOX-4, NCI-CTC grade 3/4 hematological toxicities were neutropenia and thrombocytopenia in 28 (7.6%), 1 (0.3%) of the cycles, respectively and neutropenic fever was observed in 7 cycles (1.9%). Grade 1/2 sensory neuropathy was observed in three patients (5.6%). In second-line mFOLFIRI, NCI-CTC grade 3/4 hematological toxicity was neutropenia in 20 (19.8%) of the cycles, and neutropenic fever was observed in 5 cycles (4.6%). Grade 3 diarrhea was observed in one patient (3.1%). Conclusions: As sequential chemotherapy, the mFOLFOX-4 followed by mFOLFIRI regimen is both feasible and safe for advanced gastric cancer patients. No significant financial relationships to disclose.
A novel model including CXCR4 and CDK6 as potential predictive marker for docetaxel (doc) sensitivity in gastric cancer (GC)
Authors: Wei J. , Xie L. , Qian X. , Chen G. , Yu L. , Ding Y. , Liu B. 
Published: August 2020

e15548 Background: A growing body of evidence has shed light on biomarkers for chemotherapeutic agent sensitivity in gastric cancer (GC) treatment. It has been demonstrated β-tubulin Ш (TUBB3) and microtubule associated protein tau (MAPT) might be considered as potential markers for taxanes treatment. However, an integrated predictive model for docetaxel (doc) sensitivity is still needed to customized chemotherapy in gastric cancer. Methods: Doc resistant gastric cancer cell line was established by exposure to gradually increasing doc concentration on an intermittent dosage schedule. Microarray was performed to explore different gene expression levels between parental cells and resistant cells. 11 gastrointestinal cancer cell lines were used to validate gene levels by real-time quantitative PCR as well as doc cytotoxicity. Histoculture drug response assay (HDRA) was adopted to examine doc sensitivity in 25 surgically dissected GC specimens. Discrimination analyses were used to determine which linear combinations of these genes best distinguished responder patients from nonresponder patients by adding one more genes each time. Results: After functional analysis of microarray, a panel of 11 genes were further validated, which resulting 4 genes, CXCR4 (P=0.047), CDK6 (P=0.014), USP15 (P<0.001) and CDH1 (P=0.001) that correlated to the doc sensitivity. The mRNA levels of CXCR4 and CDK6 were significantly higher in resistant GC specimens (P=0.0298, 0.022 respectively). A final response index including 5 genes (CXCR4, CDK6, USP15, TUBB3 and MAPT) showed potential predictive value for doc associated chemotherapy with an accuracy of 84% (P=0.001). Conclusions: A predictive model with five genes for doc therapy was generated and showed novel predictive role in doc sensitivity in GC. No significant financial relationships to disclose.
Neoadjuvant therapy of gastric cancer with cetuximab added to both irinotecan and cisplatin, followed by surgical resection and adjuvant chemoradiation
Authors: Ma H. Y. , Newman E. , Ryan T. , Miller G. , Sarpel U. , Pachter H. L. , Cohen D. J. , Choi H. , Goldberg J. D. , Hochster H. S. 
Published: August 2020

e15552 Background: We previously demonstrated the efficacy of irinotecan (CPT) and cisplatin (Cis) combination therapy as neoadjuvant therapy for locally advanced gastric cancer [Newman E et al. J Gastrointest Surg. 2002.]. This trial was designed to add cetuximab (C) to both induction treatment and adjuvant chemoradiation (CRT) with bolus 5-FU/LV. Methods: Pts with untreated locally advanced (T3, T4 or N+) gastric/GE cancers were eligible. Neoadjuvant therapy consisted of Cis 25mg/m2 + CPT 75mg/m2 on d1,8 q21d x 4, C 400mg/m2 on d1, then 250mg/m2 qwk. Curative (R0) resection was performed 4–6 wks later. Adjuvant CRT with 5-FU/LV (425/20/m2 qd x 5 on wks 1,14,19; 400/20/m2 qd x 4 on wk 5, x 3 on wk 9) was given with C 250mg/m2 qwk. Results: Since 11/05, 21 pts [median age 59 (32–82); 9 Caucasian, 11 Asian, 1 Hispanic; 15 male, 20 PS 0–1] received neoadjuvant therapy. The most common toxicities were gr 3 neutropenia (38%), gr 2 rash (33%), gr 2 fatigue (29%); gr 4 included 1 pt each of diarrhea, neutropenia, & hypomagnesemia. 3 did not complete neoadjuvant therapy, due to gr 3 rash, diarrhea and GI bleeding (2 had gastrectomy; 1 lost to f/u). All 18 pts who completed neoadjuvant therapy were surgically explored. 4 had occult metastases, and went off study. 14 underwent R0 gastrectomy (see table); 8 were downstaged, 2 had stable disease, 4 were upstaged compared to the preoperative EUS. There was no postoperative mortality. Of 14 resected pts, 2 did not receive adjuvant therapy (prolonged postoperative recovery), 1 too early to assess, and 11 remaining receiving CRT. The most common toxicities for CRT were gr 3 nausea, gr 3 emesis, gr 2 and 3 fatigue, 3 pts each and 1 each of gr 4 neutropenia and thrombocytopenia. Among the 18 pts who completed neoadjuvant therapy, 5 died of disease, 1 is alive with disease, 12 remain NED with median f/u of 11.6mos (4.1–27.7mos). Conclusions: The addition of C to CPT/Cis as neoadjuvant therapy and to postoperative adjuvant CRT is well tolerated. The regimen induces a favorable pathologic response on the primary tumor. Ongoing evaluation includes K-ras mutation status on outcome and survival benefit. [Supported in part by a grant from BMS.] [Table: see text]
HER2 status in 146 gastroesophageal carcinomas assessed by two rabbit monoclonal antibodies (SP3 and 4B5) and two in situ hybridisation methods (FISH and SISH)
Authors: Boers J. E. , Meeuwissen H. , Methorst N. 
Published: August 2020

e15555 Background: In the industrialized world, the incidence of adenocarcinomas of the distal esophagus/gastric cardia is increasing rapidly and though the incidence of carcinomas of the gastric body / antrum are decreasing they still represent a significant health problem. Several reports claim a significant HER2-positivity in gastro-esophageal adenocarcinomas. A large phase III trial in which HER2-positive gastric cancer patients are treated with trastuzumab is ongoing. New HER2 assessment methods are gaining popularity in breast cancer. Methods: HER2 status was examined in gastro-esophageal carcinomas, comparing SP3 (Labvision) and 4B5 (Ventana) immunohistochemistry (IHC), conventional dual probe HER2 FISH (DAKO), and SISH (Ventana) in a single Dutch institution. Results: IHC was carried out on biopsies of 146 patients with adenocarcinomas of the esophagus (n=44), gastric cardia (n=28), body (n=24) and antrum (n=50). IHC positivity, as defined by an immunoscore 2+ or 3+ using a modified scoring system, was present in 17 cases with the SP3 antibody, and in 24 cases with 4B5. FISH/SISH showed identical results in 40 cases carried out when any immunoreactivity in either antibody was detected. 100% of SP3-IHC-positive cases, and 92% of 4B5-IHC-positive were amplified. The negative predictive value of SP3 and 4B5 (immunoscores 0/1+) was 77% and 95%, respectively. Heterogenous HER2- positivity with partial staining/amplification was present in 73% of the adenocarcinomas, occasionally with only a tumor area of 10–20% showing positivity. HER2-amplification was present in 27% of esophageal and 18% in gastric cardia carcinomas (resulting in 24% amplification of tumors of the esophago-gastric region). In the distal stomach, 7% HER2-amplification was seen. Conclusions: HER2 amplification is present in a significant proportion of esophago-gastric region adenocarcinomas (24%) but at a much lower rate in the distal stomach (7%). Both antibodies can be used for initial screening for possible amplification though the 4B5 antibody has the highest negative predictive value. FISH and SISH yield identical results but the SISH assay offers rapid assessment. [Table: see text]
Phase II feasibility study of adjuvant S-1 plus docetaxel for stage III gastric cancer patients after curative D2 gastrectomy (OGSG 0604)
Authors: Fujitani K. , Tamura S. , Kimura Y. , Tsuji T. , Matsuyama J. , Iijima S. , Imamura H. , Kurokawa Y. , Tsujinaka T. , Furukawa H. 
Published: August 2020

e15567 Background: Although an adjuvant chemotherapy with S-1 has become the standard treatment for stage II-III gastric cancer (GC) patients (pts) after curative D2 gastrectomy in Japan, the survival benefit for stage III pts obtained by S-1 is considered to be modest. S-1 plus docetaxel has shown a good response rate of 56% with prolonged median overall survival (OS) of 14.3 months in pts with advanced GC. This phase II study evaluated the feasibility and safety of adjuvant S-1 plus docetaxel for stage III GC pts after R0 resection. Methods: Patients with curatively resected pathological stage III GC receiving D2 dissection, age 20–80 years, performance status < 1, no prior adjuvant treatment, adequate organ function, and informed consent were given S-1 (80 mg/m2/day) orally for consecutive 2 weeks plus docetaxel (40 mg/m2) intravenously on day 1, repeated every 3 weeks. The treatment was started within 45 days after gastrectomy, and repeated for 4 cycles, followed by S-1 monotherapy until 1 year after surgery. Study endpoints included feasibility of the 4 cycles of S-1 plus docetaxel as primary, and safety, progression free survival (PFS), and OS as secondary. Sample size was set to be 50, which was determined to reject the feasibility of 50% under the expectation of 75% with power of 90% and two-sided α of 5%. Results: Fifty-three pts, 42 males and 11 females with a median age of 65 years, were enrolled between 5/2007 and 8/2008. Pathological stages included IIIA in 36 pts and IIIB in 17 pts. Planned 4 cycles of treatment were delivered to 41 out of 53 pts, with the feasibility of 77.4% (95% CI 63.8–87.7%, P<0.001). Reasons for discontinuation were recurrent cancer in 1 pt, adverse events in 10, and miscellaneous in 1, respectively. Grade 4 neutropenia was observed in 28% of pts with grade 3 febrile neutropenia in 9%. Non-hematological toxicities of grade 3 or more involved fatigue in 6%, anorexia in 9%, and nausea in 6%. No treatment-related deaths occurred. Conclusions: Adjuvant S-1 plus docetaxel was well-tolerated and showed good compliance. Although follow-up is ongoing on survival, this regimen could be a candidate of future phase III trial seeking for the optimal adjuvant chemotherapy for stage III GC pts after curative D2 gastrectomy. No significant financial relationships to disclose.