Biliary Cancer Patients Research Articles

6639 POSTER Polymorphisms Associated With the Clinical Outcome of Biliary Tract Cancer (BTC) Patients Treated With the Epirubicin, Cisplatin and Capecitabine (ECX) Regimen

6639 POSTER Polymorphisms Associated With the Clinical Outcome of Biliary Tract Cancer (BTC) Patients Treated With the Epirubicin, Cisplatin and Capecitabine (ECX) Regimen

A comparison of competing lymph node staging schemes in resectable biliary cancer.

166 Background: New schemes for lymph node (LN) staging have been proposed to improve upon the AJCC TNM cancer staging convention. We compared AJCC N0/N1 staging with the LN ratio and logarithmic odds systems in predicting overall survival (OS) in resectable biliary cancer patients, including cancer of the gallbladder, extrahepatic bile duct (EHBD), and ampulla of Vater (AOV). Methods: In a large, multiinstitutional U.S.-based biliary cancer data set, we identified 4,288 nonmetastatic resectable biliary cancer patients diagnosed between 1988 and 2006. We compared each subject's AJCC N stage with the two novel staging schemes. We split patients into two groups above or below the median for the two novel staging schemes and analyzed OS. Our comparison metric was the log-rank chi-squared statistic. As a baseline comparator, we included the median number of LNs resected. Results: Median (range) of follow- up was 2.5 years (1 month–19 years), with an overall median survival of 2.0 years (95% CI: 2.0–2.1 years). For all biliary patients combined, we found that the AJCC N0/N1 system and LN ratio schemes performed similarly. For gallbladder cancers (N= 1,340), LN ratio showed higher OS prediction utility, whereas in EHBD (N= 1,083) and AOV cancers (N= 1,865), AJCC staging was superior among competing methods. Conclusions: The LN ratio method is comparable with AJCC N staging for OS prediction, although the AJCC scheme is superior in two of three biliary cancers. We conclude that AJCC staging remains adequate for staging biliary cancers given the newer staging proposals. [Table: see text] No significant financial relationships to disclose.

Outcomes and Tolerability of Systemic Chemotherapy for Pancreatic or Biliary Cancer Patients Aged 75 Years or Older

The incidence of pancreatic or biliary tract cancer is increasing in our aging population, but little is known of treatment outcomes in elderly patients with pancreatic or biliary tract cancer. Patients with pancreatic or biliary tract cancer who received chemotherapy in our institute between September 2007 and August 2009 were retrospectively reviewed to compare treatment outcomes between the elderly (aged 75 years or older) and the younger patients. Data were collected of patient backgrounds, adverse events and dose intensity within the first two cycles and overall survival time. Of the 102 who met the inclusion criteria, 19 were elderly who were introduced to full dose chemotherapy. Medication for their comorbidities was required in 15 (79%) of the 19 elderly patients and in 27 (33%) of 83 younger patients. The frequencies of haematological adverse events of grades 3 or 4 were 42% and 39%, and those of non-haematological adverse events were 21% and 16%, for the elderly and younger, respectively. Similar dose intensities were delivered to the elderly and younger. Also, similar proportions of elderly and younger received dose reductions. There was no difference in overall survival between the elderly and the younger. No clear difference in treatment outcomes was seen between the elderly and the younger patients who received gemcitabine alone. Gemcitabine chemotherapy appears to be safe and the same treatment effect was seen even in older patients with pancreatic or biliary tract cancer.

A phase I study of S-1 treatment with a 3 week schedule in advanced biliary cancer patients with or without hepatic dysfunction

A 3 week treatment schedule consisting of 2 weeks of S-1 therapy and 1 week of no therapy was introduced to reduce the toxicity and increase the convenience of combination chemotherapy. Hepatic dysfunction (HD) is common in patients with biliary tract cancer. A phase I study was conducted to assess the effects of a 3 week treatment schedule in Asian patients with or without HD. Forty-six patients were stratified into four groups, according to the HD criteria of the National Cancer Institute Organ Dysfunction Working Group. A three dose escalation schema was used. In the normal hepatic function group, two dose-limiting toxicity (DLT) events occurred among 12 patients at the prespecified maximal dose of 100 mg/m²/day. This dose was thereby established as the maximal tolerable dose (MTD). No DLT events were observed at the predefined maximal dose of 80 mg/m²/day in the mild HD group. In the moderate HD group, two DLT events occurred among five patients treated with 80 mg/m²/day, and the MTD was defined as 70 mg/m²/day. Two of six subjects in the severe HD group experienced DLT events at doses of 60 mg/m²/day and none developed DLT events at 50 mg/m²/day. The MTDs for a 3 week schedule of S-1 treatment were defined in patients with or without hepatic dysfunction. A 3 week treatment regimen of S-1 might be a platform for combination with newer cytotoxic agents or biologics.

Fixed dose rate infusion of gemcitabine and UFT combination chemotherapy in patients with advanced biliary cancer

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.

Palliative Therapie von Gallengangs- und Gallenblasenkarzinomen

Non-resectable cholangiocarcinoma and gallbladder carcinoma have a poor prognosis. In addition to the general aspects of "best supportive care", biliary drainage is an important part of the palliative treatment of patients with malignant biliary stenosis. Photodynamic therapy has led to an improved median survival in hilar cholangiocarcinoma in two controlled studies. The survival benefit of external radiation or intraluminal brachytherapy has not yet been convincingly demonstrated. Whether or not systemic chemotherapy should be applied is still under debate. A single study including advanced biliary and pancreatic cancer patients has demonstrated a survival benefit for the combined group. In recent years, new chemotherapy protocols have been applied, some with promising results. Intra-arterial chemotherapy and chemotherapeutically coated stents have not been evaluated well enough to be recommended outside clinical studies. Ablative therapies have been used in a limited number of patients only. Further studies are necessary to clarify whether these treatment modalities are effective.

The retrospective analysis of single agent gemcitabine for biliary tract cancers

14122 Background: At present, outcomes of advanced biliary tract cancers are dismal despite the prognosis of other many cancers are improving. Methods: We retrospectively analyzed survivals of 46 advanced biliary tract cancer patients, who were diagnosed between January 2001 and June 2005, and treated with gemcitabine 600–1,000 mg/m2 as an intravenous 30-min infusion on days 1, 8, and 15 for every 28 days, thereafter. Results: The median age was 63 (range 41–76) with 28 males and 18 females. Twenty-nine (63.0%) had no prior chemotherapy and 18 (30.4%) patients were inoperable cases. One (2.2%) achieved complete response; 5 (10.9%) achieved partial responses; 25 (54.3%) had stable diseases; 9 (19.6%) had progressive disease; and 6 (13.0%) were not evaluated for response. The median survival time and the 1 year-survival of all advanced biliary cancer patients were 8.6 months and 43.9%, respectively, those of the patients, who had the recurrence or residual cancer lesions after surgical resection were 13.5 months and 68.8%, and those of the inoperable patients were 5.4 months and 8.3%. Patients reported grade 3/4 neutropenia/leucopenia (4.3%) and grade 3 thrombocytopenia (2.2%). Grade 3 non-hematologic toxicities were general fatigue (4.3%) and renal failure (2.2%). Multivariate analysis demonstrated that history of surgical resection with tumor recurrence or with residual tumor was the independent predictors for survival. Moreover, except the features of the history of surgical resection, the prognosis of patients with low levels of serum albumin (< 3.7 g/dl) or ≥ 70 ages was worse than that of high levels of serum albumin (≥ 3.7 g/dl) or < 70 ages. Conclusions: In the treatment of biliary tract cancer, it seems that surgical resection even with possible residual tumor is beneficial for patients with good surgical candidate. The present study also suggests the possibility that the prognosis of patients with low levels of serum albumin (< 3.7 g/dl) or ≥ 70 ages might be worse than that of high levels of serum albumin (≥ 3.7 g/dl) or < 70 ages. No significant financial relationships to disclose.

Synbiotics reduce postoperative infectious complications: a randomized controlled trial in biliary cancer patients undergoing hepatectomy

The clinical value of synbiotics in surgical patients remains unclear. The aim of this study was to investigate the effect of synbiotics on intestinal integrity and microflora, as well as on surgical outcome, in patients undergoing high-risk hepatectomy. Fifty-four patients with biliary cancer were randomly allocated to two groups before hepatectomy. One group received postoperative enteral feeding that included synbiotics; the other received enteral feeding only. Lactulose/mannitol (L/M) ratio, serum diamine oxidase (DAO) activity, and fecal microflora and organic acid concentrations were determined. Postoperative infectious complications were recorded. Of the 54 patients, 44 completed the trial (21 receiving synbiotics and 23 others as controls). Postoperative changes in L/M ratios and serum DAO activities were identical between the two groups. Numbers of beneficial bacteria increased in the synbiotics group after surgery but decreased in controls. Numbers of harmful microorganisms decreased in the synbiotics group but increased in controls. Total organic acid concentrations increased in the synbiotics group but decreased in controls. Incidence of infectious complications was 19% (4/21) in the synbiotics group and 52% (12/23) in controls (P<0.05). All study patients tolerated surgery (mortality 0%). Synbiotics, combined with early enteral nutrition, can reduce postoperative infections. This beneficial effect presumably involves correction of an intestinal microbial imbalance induced by surgical stress.

Psychological Reactions in Newly Diagnosed Gastrointestinal Cancer Patients

Reactions to diagnosis, coping strategies, and anxiety and depression were prospectively studied in 139 consecutive, newly diagnosed gastrointestinal cancer patients. The reactions varied between diagnoses (colon, rectum, gastric, pancreatic and biliary) and states of illness (cured non-cured). Colon and rectal cancer patients, most of whom were potentially cured, had a more confrontational attitude towards their diagnosis, reported more ‘Fighting Spirit’ and less 'Anxious Preoccupation’ and ‘Hopeless, Helplessness'. Non-cured patients reported higher levels of intrusive thoughts and avoidance of aversive thoughts than cured patients. The overall levels of anxiety and depression were low, although higher levels were seen for non-cured patients. On the Hospital Anxiety and Depression scale (HAD), a total of 17% were scored as ‘doubtful cases’ or ‘cases’ on the anxiety scale and 21% on the depression scale. Thus, pancreatic biliary cancer patients, most of which are non-cured, and to some extent those with gastric cancer are more vulnerable to psychological distress in connection with the diagnosis than are colorectal cancer patients.

Detection of specific anti-antibodies in patients treated with radiolabeled antibody

Over 100 patients have received cyclic treatment with polyclonal 131I labeled anti-ferritin and anti-carcinoembryonic antigen (CEA) antibodies from different animal species (rabbit, pig, cynomolgous monkey, bovine, and baboon). Because survival was prolonged from original cyclic treatment, retreatment with original antibodies (recycling) became a necessary consideration. An assay using autoradiography of Ouchterlony gels, with diffusion of patients' sera against the varied radiolabeled antibodies, was developed to detect anti-antibody precipitin vands. Anti-antibody could be detected with a sensitivity to the 60 ng level. Sera from 35 patients given from 1 to 7 separate cycles (2 injections/week, total antibody 6 mg/cycle) of radiolabeled foreign antibody were studied for the production of anti-antibodies. Anti-antibodies were detected in 11 of 22 primary hepatoma patients studied, 3 of 4 intrahepatic biliary cancer patients, and 0 of 9 Hodgkin's disease patients. In all but two of the patients, the anti-antibodies produced were specific for the species used in the treatment of the patient. Eight patients were reinjected (recycled) with previously used antibodies and the presence or absence of precipitin vands correlated with the ability of these antibodies to deposit in the tumor or to be rapidly degraded. The importance of this assay is its simplicity, sensitivity, and the rapid detection of anti-antibody activity for patients requiring treatment with radiolabeled antibodies.