Cancer Survival Time Research Articles

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

Minding the body: Psychotherapy and cancer survival

This article reviews evidence regarding effects of psychotherapy on overall cancer survival time. Special emphasis is given to research on adverse effects of depression on cancer survival, breast cancer, and mediating psychophysiological pathways linking psychosocial support to longer survival. It reviews all published clinical trials addressing effects of psychotherapy on cancer survival, emphasizing depression, breast cancer, and psychophysiological evidence linking stress, depression, and support to cancer survival. Systematic literature review and synthesis. Eight of 15 published trials indicate that psychotherapy enhances cancer survival time. No studies show an adverse effect of psychotherapy on cancer survival. Potential psychophysiological mechanisms linking stress to shorter survival include dysregulation of diurnal cortisol, increased pro-inflammatory cytokines, reduced natural killer cell activity, shorter telomeres and lower telomerase activity, glucocorticoid-mediated suppression of p53 and BrCA1 gene expression, and sympathetic nervous system activation of vascular endothelial growth factor. Stress and support affect the course of cancer progression. What is known? Stress and support have been thought to be related to cancer risk and progression, but evidence has been mixed. Depression is a natural co-morbid condition with cancer. It has not been clear how stress and support could physiologically affect the rate of cancer progression. Immune function was not thought to have much relevance to cancer progression. Few other physiological mechanisms linking stress to cancer progression were known. What does this paper add? There is evidence from 15 RCTs indicating that effective psychosocial support improves quantity as well as quality of life with cancer. There is evidence that chronic depression predicts poorer prognosis with cancer. Dysregulated circadian cortisol patterns predict more rapid cancer progression. Inflammatory processes affect cancer growth and progression. Sympathetic nervous system activity, telomere length, telomerase activity, and oncogene expression are affected by stress and can affect cancer growth.

The relationship between depression and physical symptom burden in advanced cancer

BackgroundAlthough an association between depression and physical burden has been demonstrated in advanced cancer, it remains unclear to what extent this is limited to specific physical symptoms, such as pain...

Considerations for the prediction of survival time in pancreatic cancer based on registry data

Semi-parametric and parametric survival models in patients with pancreatic adenocarcinoma (PC) using data from Surveillance, Epidemiology, and End Result (SEER) registry were developed to identify relevant covariates affecting survival, verify against external patient data and predict disease outcome. Data from 82,251 patients was extracted using site and histology codes for PC in the SEER database and refined based on specific cause of death. Predictors affecting survival were selected from SEER database; the analysis dataset included 2,437 patients. Survival models were developed using both semi-parametric and parametric approaches, evaluated using Cox-Snell and deviance residuals, and predictions were assessed using an external dataset from Saint Louis University (SLU). Prediction error curves (PECs) were used to evaluate prediction performance of these models compared to Kaplan-Meier response. Median overall survival time of patients from SEER data was 5months. Our analysis shows that the PC data from SEER was best fitted by both semi-parametric and the parametric model with log-logistic distribution. Predictors that influence survival included disease stage, grade, histology, tumor size, radiation, chemotherapy, surgery, and lymph node status. Survival time predictions from the SLU dataset were comparable and PECs show that both semi-parametric and parametric models exhibit similar predictive performance. PC survival models constructed from registry data can provide a means to classify patients into risk-based subgroups, to predict disease outcome and aide in the design of future prospective randomized trials. These models can evolve to incorporate predictive biomarker and pharmacogenetic correlates once adequate causal data is established.

Leptin as a marker of undernutrition in breast cancer recurrence

ObjectiveTo relate leptin concentration with undernutrition and survival time in breast cancer recurrence.Design and methodsLeptin and other markers of undernutrition were measured in 49 patients who experienced disease recurrence for breast cancer. Undernutrition was clinically assessed by a weight loss of ≥10% between primary diagnosis and recurrence or ≥5% within the last month and/or the prescription of food supplements. Results were compared between patients with (21) or without (28) undernutrition by logistic regression models. The effect of biological variables on survival rate was assessed by the Kaplan‐Meier method.ResultsLeptin was significantly and negatively associated with undernutrition (OR=0.45 [0.23–0.87], p=0.018), while PINI (Prognostic Inflammatory and Nutritional Index, OR=1.24 [0.94–1.63], p=0.130) did not reach significance. The survival distributions across quartiles of leptin (Log rang test, p=0.048) and PINI (Log rank test, p=0.0001) were significantly different. However, as assessed by the Cox proportional hazards models, quartiles of leptin did not differ between each other while quartiles of PINI were all significantly different from quartile 1.ConclusionIn case of breast cancer recurrence, leptin is a good marker of undernutrition but is a poor marker of survival time, while PINI is a poor marker of undernutrition but is a good marker of survival time.

Higher incidence of lung adenocarcinomas induced by DMBA in connexin 43 heterozygous knockout mice.

Gap junctions are communicating junctions which are important for tissue homeostasis, and their disruption is involved in carcinogenic processes. This study aimed to verify the influence of deletion of one allele of the Connexin 43 gene on cancer incidence in different organs. The 7, 12-dimethylbenzanthracene (DMBA) carcinogenic model, using hebdomadary doses by gavage of 9 mg per animal, was used to induce tumors in Connexin 43 heterozygous or wild-type mice. The experiment began in the eighth week of the mice life, and all of them were euthanized when reaching inadequate physical condition, or at the end of 53 weeks. No statistical differences occurred for weight gain and cancer survival time (P = 0.9853) between heterozygous and wild-type mice. Cx43+/− mice presented significantly higher susceptibility to lung cancer (P = 0.0200) which was not evidenced for benign neoplasms (P = 0.3449). In addition, incidence of ovarian neoplasms was 2.5-fold higher in Cx43+/− mice, although not statistically significant. Other organs showed a very similar cancer occurrence between Cx43 groups. The experiment strengthens the evidence of the relationship between Connexin 43 deficiency and carcinogenesis.

Longitudinal health-related quality of life assessment: implications for prognosis in ovarian cancer

BackgroundThere is no information in the literature on the impact of changes in quality of life (QoL) scores on prognosis in ovarian cancer. We investigated whether changes in QoL during treatment could predict survival in ovarian cancer patients.MethodsWe evaluated 137 ovarian cancer patients treated at our institution between Jan 2001 and Dec 2009 who were available for a minimum follow-up of 3 months. QoL was evaluated at baseline and after 3 months of treatment using EORTC-QLQ-C30. Cox regression evaluated the prognostic significance of baseline and changes in QoL scores after adjusting for clinical and demographic variables.ResultsAssociations between changes in QoL and survival were observed for global function, appetite loss and constipation. Every 10-point increase (improvement) in global function from baseline to 3 months was associated with a 10% decreased risk of death (HR=0.90; 95% CI: 0.81 to 0.99, p=0.03). The corresponding HRs for 10-point increase (deterioration) in appetite loss and constipation scales were 1.20 (95% CI: 1.06 to 1.35; p=0.005) and 1.13 (95% CI: 1.02 to 1.24; p=0.02) respectively.ConclusionsThis exploratory study provides evidence that an improvement in appetite, constipation and global health scores during the first 3 months of treatment is significantly associated with improved survival time in ovarian cancer. These findings justify serial, systematic assessment of global health, appetite and constipation in ovarian cancer patients being treated, and suggest that modalities designed to improve these functions may be beneficial clinically.

Genetic variants in the integrin gene predicted microRNA-binding sites were associated with the risk of prostate cancer

microRNAs (miRNA) silence target genes through Watson-Crick based binding to the 3'untranslated regions (3'UTR). Thus, polymorphisms in the miRNA-binding sites may disrupt this process and play a potential role in cancer pathogenesis. Integrins have been implicated in the genesis and development of many tumors. This study was designed to evaluate the association between five SNP loci in predicted miRNA-binding sites in five integrin genes and prostate cancer occurrence and prognosis to provide data for screening high-risk Chinese Han individuals. These five polymorphisms were genotyped by using the high-resolution melting method (HRM) in 347 Chinese Han prostate cancer patients with long-time follow-up together with 367 age-matched healthy controls. GC carriers of rs11902171 in ITGAv were associated with a decreased risk of prostate cancer (OR 0.57, 95% CI 0.35-0.93). However, no significant difference was detected in genotype distributions of the five SNP loci in the progression-free survival time of prostate cancer. The ITGAv gene SNP rs11902171 may be potentially associated with the risk of prostate cancer.

1681P - The Role of Macrophages Polarization in Predicting Prognosis in Radically Resected Gastric Cancer

ABSTRACT Introduction Macrophages are one of the major populations of tumor-infiltrating immune cells. Tumor associated Macrophages (TAM) present two different phenotypes or polarizations: classical (M1) characterized by immunostimulation activity and tumor suppression; alternative (M2) characterized by angiogenesis, tumor promotion, and immune suppression. Despite these opposite properties, most of the previous studies focused merely on evaluating absolute TAM count. In this work, for the first time in literature, we evaluated the correlation between the two forms of TAM with survival time in patients affected by gastric cancer after radical surgery. Methods 52 chemo- and radio-naive gastric cancer patients undergone to resection for curative intent were included in this retrospective study. Two slides were prepared for each patients and double-stained for CD68/NOS2 (M1) or CD68/CD163 (M2) and five representative high-power fields (×400 magnification) per slide were evaluated for TAM count. The median value of the two macrophage populations density (M1 = 7.0; M2 = 6.4) and the median value of M1/M2 ratio (1.16) was used as cut-off. Results 27 patients with M1 density above the median had a significantly higher survival compared to those below the median (median OS of 25.6 months, CI95%:22.33-44.85 vs 17.1 months, CI95%:13.66-27.98; P = 0.041). 26 patients with M1/M2 ratio above the median showed median OS of 27.2 months (CI95%:25.45-47.51) compared to 15.5 months (CI95%:11.36-25.50) of the patients below the median (P = 0.001). No statistically significant difference in terms of M1/M2 ratio was observed between intestinal vs diffuse histological type. No association between M2 macrophage density and patients outcome (P= 0.724) was found. In multivariate analysis M1/M2 was a positive independent predictor of survival (P= 0.001; HR 0.420, CI95%: 0.22-0.78) whereas grading, histotype and TNM stage were not statistically significant. Conclusion The M1 macrophage density and in particular M1/M2 ratio, as confirmed in multivariate analysis, is an independent factor that can predict patients survival time in gastric cancer after radical surgery. The role of macrophage phenotype in influencing the gastric cancer prognosis warrant further investigation. Disclosure All authors have declared no conflicts of interest.

Chronic Hepatic Viral Infection Could be a Protective Factor for Colorectal Cancer Liver Metastases: Analysis in a Single Institute

We tested the hypothesis that chronic hepatic virus infection could reduce the occurrence of colorectal cancer liver metastases (CLM) and investigated CLM patients' survival prolonged in positive viral infection. 2868 colorectal cancer patients were divided into positive-infection and non-infection groups. Clinical variables, incidence of liver metastases and survival between the groups were respectively analyzed. The incidence of liver metastases in the positive group was much lower than in the control group, but other type distant metastasis was similar in the two groups. Infected group 5-year overall survival (OS) was better than the negative group. Meanwhile, CLM patients in the former group showed longer survival time than the control group (26 months vs. 20 months, p<0.001). Chronic hepatic viral infection could reduce the occurrence of CLM and improves the survival time of colorectal cancer. It could be a protective factor for CLM patients.

HER2 monoclonal antibody conjugated RNase-A-associated CdTe quantum dots for targeted imaging and therapy of gastric cancer

Successful development of safe and effective nanoprobes for targeted imaging and selective therapy of in-situ gastric cancer is a great challenge. Herein, one kind of multifunctional HER2 monoclonal antibody conjugated RNase A-associated CdTe quantum dot cluster (HER2-RQDs) nanoprobes was prepared, its cytotoxicity was evaluated. Subcutaneous gastric cancer nude mouse models and in-situ gastric cancer SCID mouse models were established, and were intravenously injected HER2-RQDs nanoprobes, the bio-distribution and therapeutic effects of HER2-RQDs in vivo were evaluated. Results showed that HER2-RQDs nanoprobes could selectively kill gastric cancer MGC803 cells, could target imaging subcutaneous gastric cancer cells at 3 h post-injection, and in-situ gastric cancer cells at 6 h post-injection, and could inhibit the growth of gastric cancer tissues and extended survival time of gastric cancer bearing mouse models, which is closely associated with destroying functional RNAs in cytoplasm by RNase A released from HER2-RQDs nanoprobes, preventing protein synthesis and inducing cell apoptosis. High-performance HER2-RQDs nanoprobes exhibit great potential in applications such as in-situ gastric cancer targeted imaging, and selective therapy in the near future.

Pathway-based classification of cancer subtypes

BackgroundMolecular markers based on gene expression profiles have been used in experimental and clinical settings to distinguish cancerous tumors in stage, grade, survival time, metastasis, and drug sensitivity. However, most significant gene markers are unstable (not reproducible) among data sets. We introduce a standardized method for representing cancer markers as 2-level hierarchical feature vectors, with a basic gene level as well as a second level of (more stable) pathway markers, for the purpose of discriminating cancer subtypes. This extends standard gene expression arrays with new pathway-level activation features obtained directly from off-the-shelf gene set enrichment algorithms such as GSEA. Such so-called pathway-based expression arrays are significantly more reproducible across datasets. Such reproducibility will be important for clinical usefulness of genomic markers, and augment currently accepted cancer classification protocols.ResultsThe present method produced more stable (reproducible) pathway-based markers for discriminating breast cancer metastasis and ovarian cancer survival time. Between two datasets for breast cancer metastasis, the intersection of standard significant gene biomarkers totaled 7.47% of selected genes, compared to 17.65% using pathway-based markers; the corresponding percentages for ovarian cancer datasets were 20.65% and 33.33% respectively. Three pathways, consisting of Type_1_diabetes mellitus, Cytokine-cytokine_receptor_interaction and Hedgehog_signaling (all previously implicated in cancer), are enriched in both the ovarian long survival and breast non-metastasis groups. In addition, integrating pathway and gene information, we identified five (ID4, ANXA4, CXCL9, MYLK, FBXL7) and six (SQLE, E2F1, PTTG1, TSTA3, BUB1B, MAD2L1) known cancer genes significant for ovarian and breast cancer respectively.ConclusionsStandardizing the analysis of genomic data in the process of cancer staging, classification and analysis is important as it has implications for both pre-clinical as well as clinical studies. The paradigm of diagnosis and prediction using pathway-based biomarkers as features can be an important part of the process of biomarker-based cancer analysis, and the resulting canonical (clinically reproducible) biomarkers can be important in standardizing genomic data. We expect that identification of such canonical biomarkers will improve clinical utility of high-throughput datasets for diagnostic and prognostic applications.ReviewersThis article was reviewed by John McDonald (nominated by I. King Jordon), Eugene Koonin, Nathan Bowen (nominated by I. King Jordon), and Ekaterina Kotelnikova (nominated by Mikhail Gelfand).

PCN25 Effect of Treatments for Late-Stage Prostate Cancer on Survival

This study examined the relative effectiveness of treatments increasing the survival time for late-stage prostate cancer. Cox proportional hazard regression model was used to assess overall survival in relation to various treatments adjusting for confounding factors. Survival time was calculated from the date of initial diagnosis to the last day of contact. Patient demographics, type of health insurance stage, and grade of the tumor were extracted from Florida Cancer Data System. Socioeconomic factors were extracted from Census 2000. The types of co-morbidity were formulated following the Elixhauser Index. The Census 2000 and Florida Agency for Health Care and Administration datasets were linked with the Florida Cancer Data system for the time between October 1, 2001 and December 31, 2007 with survival being measured through October 31, 2008. A total of 4336 men who had late-stage prostate cancer in Florida were analyzed. The average age at the time of diagnosis was 65 and the average survival time was 253 days. Among patients who had late-stage prostate cancer, 59 percent received surgical treatment only. The log-rank and Wilcoxon tests indicated that there were significant differences in survival time by treatment options. The cox proportional hazard regression result showed that patients who had received radiation only, hormone only, and those who had chosen active surveillance were at a higher risk of having shorter survival time than those who had received surgery only. The existence of one or more co-morbidity, being diagnosed at an older age, and being uninsured were associated with higher mortality. The study found that men who received the following treatments received radiation only, hormone only, chose active surveillance, with co-morbidity and of advanced age had lower survival benefit. Further, research that is foucsed on the specific cause of death may help understand the impacts of treatment and covariates on prostate cancer survival.

Analysis of clinicopathological characteristics and survival time of penile cancer after surgery

Objective To analyze the clinicopathological characteristics and survival time of penile cancer after surgery. Methods The clinicopathological data of 93 cases of penile cancers patients treated from January 2002 to December 2010 were collected retrospectively.The Kaplan-Meier method was used to draw the survival function and calculate the survival rate.Log-rank test was further used to compare survival difference. Results The median age of the 93 patients was 51 years ( range,23 to 82).Squamous carcinoma was most common with 87 eases (93.5％) in our group.Sixty-one patients were successfully followed up and the median follow up duration was 28 months(range,2 to 89 months).All 3 cases of verrucous carcinoma had progression free survive after surgery after follow up of 12,19,and 67 months.In the 55 patients with penile invasive squamous carcinoma,11 patients died of metastatic disease with a median survival time of 10 months ( range,2 to 24 months).Two years cumulative survival rate was 75.7％ (95％ CI 63.0％ to 88.4％ ).Six cases of 12 patients with lymph node metastasis died of penile cancer while only 5 cases of 43 patients without lymphnode metastasis died.The survival difference was significant (log rank,P =0.000). Conclusions Squamous carcinoma is the most common type,and patients with lymphnode metastasis have poor prognosis.Verrucous carcinoma has good prognosis. Key words: Penile neoplasms; Carcinoma,squamous cell; Carcinoma,verrucous; Survival analysis

Association Between Colorectal Cancer Susceptibility Loci and Survival Time After Diagnosis With Colorectal Cancer

Genome-wide association studies have identified 16 germline single-nucleotide polymorphisms (SNPs) that are associated with colorectal cancer (CRC) incidence. We examined the relationship between these SNPs and survival of 2611 individuals with CRC, enrolled in 5 cohort studies. We used Cox regression analysis to associate SNPs with overall and CRC-specific survival times. The minor allele in rs4939827 (SMAD7) was associated with reduced overall survival (hazard ratio, 1.16; 95% confidence interval, 1.06-1.27; P = .002) and disease-specific survival (hazard ratio, 1.17; 95% confidence interval, 1.05-1.30; P = .005). Other SNPs were not associated significantly with survival. Common germline variations might be prognostic factors for patients with CRC. A variant in SMAD7 could affect progression of CRC.

A transformation class for spatio-temporal survival data with a cure fraction

We propose a hierarchical Bayesian methodology to model spatially or spatio-temporal clustered survival data with possibility of cure. A flexible continuous transformation class of survival curves indexed by a single parameter is used. This transformation model is a larger class of models containing two special cases of the well-known existing models: the proportional hazard and the proportional odds models. The survival curve is modeled as a function of a baseline cumulative distribution function, cure rates, and spatio-temporal frailties. The cure rates are modeled through a covariate link specification and the spatial frailties are specified using a conditionally autoregressive model with time-varying parameters resulting in a spatio-temporal formulation. The likelihood function is formulated assuming that the single parameter controlling the transformation is unknown and full conditional distributions are derived. A model with a non-parametric baseline cumulative distribution function is implemented and a Markov chain Monte Carlo algorithm is specified to obtain the usual posterior estimates, smoothed by regional level maps of spatio-temporal frailties and cure rates. Finally, we apply our methodology to melanoma cancer survival times for patients diagnosed in the state of New Jersey between 2000 and 2007, and with follow-up time until 2007.

Paraoxonase 1 (PON1) as a marker of short term death in breast cancer recurrence

ObjectiveTo relate paraoxonase (PON1) activity to survival time and short term death in breast cancer recurrence.Design and methodsPON1 activity was measured by its rate of hydrolysis of two different substrates, paraoxon (PON) and phenylacetate (ARE) in 50 patients who experienced disease recurrence for breast cancer. Results were compared between patients surviving more than one year after the analysis (n=22) and those who died within one year (n=28).ResultsIn a logistic regression analysis, ARE was significantly and negatively associated with early death (OR = 0.10 [0.02–0.58], p=0.0109). PON did not reach significance (OR = 0.43 [0.17–1.11], p=0.0826). As assessed by the Kaplan‐Meier method, the survival distributions across quartiles of ARE was significantly different (Log rang test, p=0.0393). The Cox proportional hazards model indicated that quartile 1 of ARE was significantly different from quartile 4 (HR= 5.48 [1.48–20.36], p=0.0110. In a multiple logistic regression analysis model, ARE was independently associated with early death (OR = 0.12 [0.02–0.98], p=0.0476), besides interval time between diagnosis and recurrence (OR = 0.54 [0.27–1.07], p=0.0781) and undernutrition (OR = 3.95 [0.81–19.19], p=0.0883).ConclusionParaoxonase activity may predict survival in patients with breast cancer recurrence.

The Insertion of Self Expanding Metal Stents With Flexible Bronchoscopy Under Sedation for Malignant Tracheobronchial Stenosis: A Single-Center Retrospective Analysis

ObjectiveTo describe a 10-year experience of inserting Ultraflex™ self-expanding metal stents (SEMS) under sedation using flexible bronchoscopy for the treatment of malignant tracheobronchial stenosis in a tertiary referral center. MethodsMedical notes were retrospectively reviewed for all patients who underwent SEMS insertion between 1999 and 2009. ResultsA data analysis of 68 patients who had Ultraflex™ SEMS inserted under sedation was completed. Thirty-three males and 35 females with a mean age of 67.9 years (range 35–94) presented with features including dyspnea/respiratory distress (39 patients), stridor (16 patients), and hemoptysis/dyspnea (13 patients). Etiology of stenosis included lung cancer (46 patients), esophageal cancer (14 patients), and other malignancies (8 patients). Mean dose of midazolam administered was 5mg (range 0–10mg). The trachea was the most common site of stent insertion followed by the right and left main bronchus, respectively. Adjuvant laser therapy was applied at some stage in 31% of all cases, and chemotherapy and/or radiotherapy was administered to at least 64% of patients with malignant disease.Hemoptysis and stent migration were the most frequent complications (5 and 4 patients, respectively). The mean survival time of stented non-small cell lung cancer (NSCLC) patients was 214 days (range 5–1233) and that of esophageal malignancy was 70 days (range 12–249). Mean pack-year history of individuals with lung cancer requiring stent insertion was 37 (range 2–100). ConclusionUltraflex stents offer a safe and effective therapy for patients who are inoperable or unresectable that otherwise would have no alternative therapy. It has an immediate beneficial effect upon patients, not only through symptom relief but also, in some, through prolongation of life. Survival data are no worse than other studies using different varieties of stents and insertion techniques indicating its longer-term efficacy. Moreover, this report highlights the feasibility of performing this procedure successfully in a respiratory unit, without the need for general anesthesia.

Traditional Chinese Medicinal Syndromes and Treatment in Colorectal Cancer

Colorectal cancer remains the third most common malignancy worldwide. According to the principles of Traditional Chinese Medicine (TCM), colorectal cancer is related to spleen-deficiency, damp-heat, and toxicity accumulation. Traditional Chinese medicine has been confirmed to effectively reduce toxic side effects and enhance curative effects of chemotherapy, palliate clinical syndrome, prevent recurrence and metastasis, improve quality of life and immune function, and prolong survival time in colorectal cancer. However, TCM theoretical and syndrome differentiation study has lagged far behind due to progression of therapy model in colorectal cancer. As a type of drug treatment, there are some common biological basis between chemotherapy, targeted therapy and anti-cancer herb therapy in colorectal cancer, such as apoptosis, cell senescence and autophagy. There are growing needs to explore the effect mechanism and compatibility of anti-cancer herbs, to further enhance the efficacy of TCM treatment in colorectal cancer.

Efficacy and Safety of Gemcitabine Monotherapy for Patients with Advanced Biliary Tract Cancer

The aim of this study was to analyze the efficacy and feasibility of gemcitabine monotherapy in patients with unresectable advanced or recurrent biliary tract cancer (BTC). Six patients with unresectable advanced BTC and 12 patients with recurrent BTC received gemcitabine monotherapy. Gemcitabine (800-1,000 mg/m²) was administered intravenously over 30 minutes on days 1, 8, and 15 every 28 days. Disease and toxicity were assessed once a week in all patients until the completion of gemcitabine treatment. Computed tomographic/magnetic resonance imaging studies were done every 8 weeks during chemotherapy, and every 4 weeks if progressive disease was suspected. Tumor response was determined according to the Response Evaluation Criteria in Solid Tumors. Toxicity was assessed using the National Cancer Institute Common Toxicity Criteria version 2.0. The time to progression and survival time were also calculated. In patients with unresectable BTC, the overall response rate and the median time to progression for patients with partial response or stable disease was 66.7% and 5.68 months, respectively. Clinical benefit was observed in 3 patients with stable disease (50%). The median survival time was 5.2 months. In patients with recurrent BTC, 4 patients (33%) obtained partial responses and 2 patients (17%) had stable disease. The median time to progression was 8.2 months. Six of 12 patients (50%) obtained clinical benefit. The median survival time for cancer of the intrahepatic bile duct, the extrahepatic bile duct, and the ampulla of Vater were 2.8 months, 8.5 months, and 10.7 months, respectively. No significant correlation between the survival time and the resectability of the initial procedure (R number) was detected. The survival time for patients with a performance status of 0 or 1 was significantly longer than that for patients with a performance status of 2 (P=0.0051). Neither grade 3/4 hematologic toxicity nor grade 3/4 nonhematologic toxicity was observed. No treatment-related deaths were observed. Gemcitabine monotherapy may provide a more favorable prognosis in patients with advanced BTC than does best supportive care alone. Moreover, this regimen may represent a therapeutic option for the adjuvant setting in patients with BTC.