Effect Of Neoadjuvant Chemoradiation Therapy Research Articles

Serum hsa-miR-30e As a Potential Biomarker to Predict the Effect of Neoadjuvant Chemoradiation Therapy in Locally Advanced Rectal Cancer.

Objective: To identify serum microRNAs (miRNAs) correlated with response to neoadjuvant chemoradiation therapy (NCRT) in locally advanced rectal cancer (LARC) patients using in silico analysis and laboratory validation studies. Methods: GSE68204 and GSE68204 data sets were analyzed to identify differentially expressed (DE) miRNAs in NCRT responders using the GEO2R Limma package within the R software suite. Then we used quantitative real-time polymerase chain reaction to detect the upregulated target miRNAs in the serum of 20 LARC patients. Logistic regression was used to evaluate the effect of serum miRNA level on response. Gene Ontology and pathway enrichment analyses were performed to predict the corresponding functions of the DE miRNAs. Correlation between the expression of the hub target genes and the abundance of tumor-infiltrating lymphocytes was further investigated. Results: hsa-miR-30e and hsa-miR-210 were verified to be upregulated in tumor tissues of NCRT responders. Subsequent liquid-biopsy studies revealed that the serum level of miR-30e was associated with a 2.47-fold increased incidence of NCRT-responsive patients in comparison with nonresponders (p-value = 0.038, Mann-Whitney test). Nine hub target genes of hsa-miR-30e were enriched in pathways including immune regulation. The expression of these hub target genes was correlated with abundance of tumor-infiltrating lymphocytes. Conclusion: In summary, hsa-miR-30e was determined to be upregulated in rectal cancer tissues of NCRT-responders. Further investigations showed that increased serum levels of hsa-miR-30e were associated with an effective NCRT response in LARC patients.

Choline metabolism is associated with pathological response and recurrence of patients with pancreatic cancer after neoadjuvant chemoradiation therapy

Introduction: Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis even if it is resectable. Although the efficacy of neoadjuvant therapies for PDAC are reported in recent years, it is still unclear the optimal target of neoadjuvant therapy. We investigated the metabolic changes in PDAC to identify mechanisms of treatment effect of neoadjuvant chemoradiation therapy (NACRT). Methods: Frozen tissue of tumor and normal pancreas were obtained from 49 patients with PDAC who underwent surgery. There were 30 patients who received NACRT (NACRT group) and 19 patients who did not receive any neoadjuvant therapy (control group). Metabolites levels of tumor and normal pancreatic tissue were measured by capillary electrophoresis-mass spectrometry (CE-MS). In NACRT group, pathological responses were classified according to Evans grade (evans grade Ⅰ～ⅡA; resistant group (n=19), ⅡB～Ⅳ; response group (n=10) ). RNA microarray was also performed for NACRT group (10 patients) and control group (5 patients). Results: In comparison of metabolite levels of tumor, there were significant differences in 22 metabolites between NACRT group and control group. There were significant differences in 9 metabolites between response group and resistant group. Among these 9 metabolites, only phosphocholine was associated with recurrence in NACRT group. RNA microarray showed marked gene suppression of choline transporter in PDAC tissue of NACRT group. Conclusion: Present study, identify new metabolic consequences of PDAC and potential target of NACRT. Choline metabolism is associated with pathological responses and prognosis in patients with PDAC who received NACRT.

The prognostic impact of neoadjuvant chemoradiotherapy on lymph node sampling in patients with locally advanced rectal cancer

According to the American Joint Committee on Cancer, at least 12 lymph nodes are required to accurately stage locally advanced rectal cancer (LARC). Neoadjuvant chemoradiation therapy (NACRT) reduces the number of lymph nodes retrieved during surgery. In this study, we evaluated the effect of NACRT on lymph node retrieval and prognosis in patients with LARC. We performed an observational study of 142 patients with LARC. Although our analysis was retrospective, data were collected prospectively. Half the patients were treated with NACRT and total mesorectal excision (TME) and the other half underwent TME only. The number of lymph nodes retrieved and the number of metastatic lymph nodes were significantly reduced in the NACRT group (P > 0.001). In the univariate and multivariate analyses, only NACRT and patient age were significantly associated with reduced lymph node retrieval. The number of metastatic lymph nodes and the lymph node ratio (LNR) both had a significant effect on prognosis when the patient population was examined as a whole (P = 0.003 and P = 0.001, respectively). However, the LNR was the only significant, independent prognostic factor in both treatment groups (P = 0.007 for the NACRT group; P = 0.04 for the no-NACRT group). NACRT improves patient prognosis only when the number of metastatic lymph nodes is reduced. The number of metastatic lymph nodes and the LNR are important prognostic factors. Lymph node retrieval remains an indispensable tool for staging and prognostic assessment of patients with rectal carcinoma treated with NACRT.

Changes in Indoleamine 2,3-Dioxygenase 1 Expression and CD8+ Tumor-Infiltrating Lymphocytes after Neoadjuvant Chemoradiation Therapy and Prognostic Significance in Esophageal Squamous Cell Carcinoma

Despite good preclinical evidence, clinical data on the effect of neoadjuvant chemoradiation therapy (CRT) on expression of immune markers in esophageal cancer are limited. This study aimed to evaluate the changes in indoleamine 2,3-dioxygenase 1 (IDO1) expression, programmed cell death-ligand 1 (PD-L1) expression, and CD8+ tumor-infiltrating lymphocyte status after neoadjuvant CRT and the prognostic significance in esophageal squamous cell carcinoma (ESCC). Between 2003 and 2017, 138 patients with ESCC who underwent neoadjuvant CRT and esophagectomy without achieving pathologic complete response were included for analysis. Both pre-CRT biopsies and post-CRT surgical specimens were available in 82 patients. Immunohistochemistry of IDO1, PD-L1, and CD8 density were analyzed. Among 82 paired samples, the expression levels of IDO1 and PD-L1 and CD8 density increased significantly after neoadjuvant CRT (P < .01 for all). Patients with high IDO1 expression after CRT had poorer overall survival (P = .001) and recurrence-free survival (P < .001) than those with low IDO1 expression. High post-CRT CD8 density was significantly correlated with more favorable overall survival (P = .01) and recurrence-free survival (P = .008). Neither pre- nor post-CRT PD-L1 expression was an independent prognostic factor for survival. Stratification analysis revealed that patients with combined low IDO1 expression and high CD8 density after CRT were significantly associated with better survival than other subgroups. The major findings were reproducible in an independent validation cohort. IDO1 and PD-L1 expression and CD8 density increased significantly after neoadjuvant CRT in ESCC. The post-CRT IDO1 expression and CD8 density could serve as prognostic biomarkers for survival.

The effects of neoadjuvant chemo-radiation therapy and neoadjuvant chemotherapy on the occurrence of post-operative complications in patients with esophageal cancer underwent surgery

The effects of neoadjuvant chemo-radiation therapy and neoadjuvant chemotherapy on the occurrence of post-operative complications in patients with esophageal cancer underwent surgery

Preoperative MDCT Assessment of Resectability in Borderline Resectable Pancreatic Cancer: Effect of Neoadjuvant Chemoradiation Therapy.

The purpose of this study is to evaluate the diagnostic performance of MDCT in assessing tumor resectability in patients with borderline resectable pancreatic cancers after receiving neoadjuvant chemoradiation therapy (CRT) in comparison with those undergoing upfront surgery. Thirty-seven patients with borderline resectable pancreatic cancers were randomly allocated to the neoadjuvant CRT group (arm 1; n = 18) or up-front surgery group (arm 2; n = 19). Three radiologists rated the likelihood of local resectability on a 5-point scale at preoperative MDCT in two separate sessions (session 1: post-CRT of arm 1, baseline of arm 2; session 2: using new imaging criteria reflecting the changes during CRT of arm 1). The AUC of each reviewer, as well as sensitivity, specificity, and accuracy based on consensus interpretation, were compared between arms and sessions. For local resectability (n = 30), AUC values at session 1 were 0.664, 0.669, and 0.588 for reviewers 1, 2, and 3, respectively, and were not significantly different between arms 1 (n = 15; 0.759, 0.713, and 0.593) and 2 (n = 15; 0.852, 0.685, and 0.722) (p > 0.05). In arm 1, MDCT sensitivity, specificity, accuracy were 22%, 100%, and 53%, respectively, at session 1 versus 78%, 67%, and 73%, respectively, at session 2 (p > 0.05). In patients with borderline resectable pancreatic cancers, neoadjuvant CRT did not significantly decrease the performance of MDCT for the prediction of local resectability. However, by considering post-CRT changes, such as nonprogression in tumor-vascular contact, MDCT may provide better sensitivity for locally resectable disease.

Correlation Between Biomarker Candidate Proteins with the Effect of Neoadjuvant Chemoradiation Therapy on Esophageal Squamous Cell Carcinoma.

While chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC), it is important to predict response prior to treatment by using markers because some patients respond well and others do not. Fifty-nine patients with ESCC were treated with neoadjuvant CRT at the Kagoshima University Hospital. The expression of seven types of biomarker candidate proteins in biopsy specimens of untreated primary tumors was evaluated to determine whether it correlated with response and prognosis. The positive expression rates were 47% for p53, 83% for CDC25B, 68% for 14-3-3sigma, 76% for p53R2, 75% for ERCC1, 32% for Gli-1, and 54% for Nrf2. In terms of histological response, tumor grade of the 59 patients was 48.8% for grade 1 as the non-responder, 29.2% for grade 2, and 22.0% for grade 3 as the responder. CRT was significantly effective in p53(-), p53R2(-), ERCC1(-), and Nrf2(-) tumors, while p53(-), p53R2(-), and ERCC1(-) were factors independently correlated with effective histological response. Their combined expression of two or three negative expressions had 100% effective response and was a significant prognostic factor. Our results suggest that two or three negative expressions of p53, p53R2, and ERCC1 in biopsy specimens of primary tumors were associated with a favorable response to CRT for ESCC. Assessment of tumor suppressor and DNA repair protein expressions in biopsy specimens may be useful for the potential utility of CRT therapy for patients with ESCC prior to treatment.

Effect of Neoadjuvant Chemoradiation Therapy on Proteasome Pool in Rectal Cancer.

In untreated rectal cancer patients, the chymotrypsin-like activity of proteasomes in tumor tissue was 3-fold higher than that in conventionally normal tissue, which is explained by up-regulation of expression of immunoproteasomes and total pool of proteasomes. After neoadjuvant chemoradiation therapy, expressions of the total pool of proteasomes and immunoproteasomes in the tumor as well as the relative ratios of these indices to those in conventionally normal tissue were smaller by 1.4-3.3 times in comparison with the untreated patients. These changes were paralleled with pronounced (4.5-fold) down-regulation of proteasome activity in the tumor and a 3.7-fold decrease of activity ratio for the proteasomes in tumor and in conventionally normal tissue. The number of immunoproteasome subunits and the chymotrypsin-like activity of proteasomes can be viewed as potential markers to prognosticate effectiveness of neoadjuvant chemoradiation therapy in rectal cancer patients.

Comparative Quantitative Lymph Node Assessment in Localized Esophageal Cancer Patients After R0 Resection With and Without Neoadjuvant Chemoradiation Therapy

IntroductionThe effects of neoadjuvant chemoradiation therapy on lymph node retrieval during esophagectomy for patients with esophageal cancer are unclear. The aim of this study was to quantify lymph node retrieval after R0 esophagectomy and to assess its impact on overall survival in induction therapy patients. MethodsOne hundred seventy-four consecutive patients underwent esophagectomy with or without induction therapy from 2008 to 2015 for esophageal cancer. Total lymph nodes, positive lymph nodes, and lymph node ratios were compared between two groups of patients: those treated with either upfront surgery or those treated with neoadjuvant chemoradiation therapy followed by surgery. Comparisons were made using Student’s t test. Overall survival was obtained and compared using Kaplan Meier survival curves. ResultsTotal lymph node counts were less in the induction therapy group (p = 0.027), while positive lymph node counts and lymph node ratios did not differ between groups (p = 0.262 and p = 0.310, respectively). In the neoadjuvant chemoradiation followed by surgery group, overall survival was significantly shorter for patients who had any positive lymph nodes in the pathologic specimen (p = 0.0065). ConclusionsTotal lymph node counts were significantly lower in the induction therapy group, while positive lymph node counts and lymph node ratios did not differ from the upfront surgery group. Although overall survival was not different between groups, it was decreased within the induction therapy cohort among those who had any positive lymph nodes retrieved at surgery. This study confirms that unstratified gross lymph node counts do not substantially relate to prognosis in the heterogeneous population of locally advanced esophageal cancer patients who may or may not have had neoadjuvant chemoradiation.

Short–term effects of neoadjuvant chemoradiation therapy on anorectal function in rectal cancer patients: a pilot study

BackgroundNeoadjuvant chemoradiation therapy followed by curative surgery has gained acceptance as the therapy of choice in locally advanced rectal cancer. However, deterioration of anorectal function after long-course neoadjuvant chemoradiation therapy combined with surgery for rectal cancer is poorly defined. The aim of this study was to evaluate the physiological and clinical change of anorectal function after neoadjuvant chemoradiation therapy for rectal cancer.MethodsWe analyzed 30 patients on whom preoperative anorectal manometry data were available both before and after chemoradiation from October 2010 to September 2011. All patients underwent long-course neoadjuvant chemoradiation therapy. We compared manometric parameters between before and after neoadjuvant chemoradiation therapy.ResultsOf 30 patients, 20 were males and 10 females. The mean age was 64.9 ± 9.9 years (range, 48-82). Before nCRT, the rectal compliance was higher in patients with ulceroinfiltrative type (P = 0.035) and greater involvement of luminal circumference (P = 0.017). However, there was the tendency of increased rectal sensory threshold for desire to defecate when the patient had decreased circumferential ratio of the tumor (P = 0.099), down-graded T stage (P = 0.016), or reduced tumor volume (P = 0.063) after neoadjuvant chemoradiation.ConclusionsNeoadjuvant chemoradiation therapy did not significantly impair overall sphincter function before radical operation. The relationship between tumor response of chemoradiation and sensory threshold for desire to defecate may suggest that neoadjuvant chemoradiation may be helpful for defecatory function as well as local disease control, at least in the short-term period after the radiation in locally advanced rectal cancer patients.

Treatment Effect of Neoadjuvant Chemoradiation Therapy for Non-small Cell Lung Cancer Evaluated by Multimodality Imaging and Histopathological Analyses

Purpose/Objective(s): To assess treatment effect of neoadjuvant chemoradiation therapy (NACRT) for locally advanced non-small cell lung cancer (LA-NSCLC) by multi-modality imaging and histopathological diagnosis including molecular biological analyses. Materials/Methods: We retrospectively reviewed the radiation oncology and histopathological records of 11 patients who underwent NACRT for LA-NSCLC and contrast enhanced computed tomography (CECT), magnetic resonance imaging (MRI), and positron emission tomography CT before and after NACRT between 2007 and 2010. There were 10 males and 1 female with a median age of 68 years (range, 54 to 76). Eight had squamous cell carcinomas, one had large cell carcinoma, one had adenocarcinoma, and one was unclassified. NACRT consisted of 2 cycles of cisplatin and vinorelbine-based chemotherapy given concurrently with 3D conformal radiation therapy of 40 Gy in 20 fractions within 4 weeks. Changes of tumor findings on imaging were compared with histopathological diagnosis including molecular biological analyses using immunostaining technique of the surgical specimens. Results: Histopathological manifestation of the Hematoxylin-Eosin stained surgical specimens showed Effect 3 (Ef. 3: no viable tumor cells) in 6 and Effect 2 (Ef. 2: small amount of remnant viable tumor cells) in 5, and negative surgical margin was observed in all cases. Positive ratios of growing cell in remnant viable tumor cells of Ef. 2 cases were less than 15% and positive ratios of double strand breaks were more than 50%. Mean reduction ratio of tumor size on CECT in cases of Ef. 2 and EF. 3 were 38% and 55%. Mean reduction ratios of SUV in cases of Ef. 2 and EF. 3 were 56% and 83%. One case with EF. 3 showed persistent Ffluorodeoxy glucose accumulation at margin of tumor due to inflammatory cells infiltration around necrosis. Signal intensity changes of tumor on diffusion weighted images of MRI did not correlate with histopathological treatment effect. Conclusions: High reduction ratio of tumor size and SUV tended to correlate with good histopathological treatment effect of NACRT for NSCLC. Even if the remnant viable tumor cells were present morphologically in the surgical specimens, more than 50% of them had double strand breaks of DNA and growing cell ratios were less than 15%. Author Disclosure: H. Ikushima: None. K. Kondo: None. Y. Otomi: None. H. Maezawa: None.

Does Neoadjuvant Therapy Alter KRAS and/or MSI Results in Rectal Adenocarcinoma Testing?

To our knowledge, the genotoxic effects of neoadjuvant chemoradiation therapy on molecular diagnostic testing results are unknown. However, if neoadjuvant treatments were to alter molecular test results, clinical decision-making could be misled. This raises questions about the appropriateness of using posttreatment tumor for testing. To address this, rectal adenocarcinomas both before and after neoadjuvant treatment were evaluated for alterations in KRAS and microsatellite instability (MSI) testing. Neoadjuvant chemoradiation therapy is common in this tumor type, and alterations in these 2 tests would significantly impact management. A total of 17 rectal adenocarcinoma patients with available pretreatment and posttreatment tumor were studied. MSI testing used the revised National Cancer Institute panel of 5 mononucleotide microsatellite repeats, comparing cancers with matched normal control tissues. KRAS codon 12-point and 13-point mutations were examined by polymerase chain reaction amplification and bidirectional sequencing. MSI and KRAS results were unchanged comparing rectal cancer tissue before and after chemoradiotherapy in all 17 patients (P=1.000; 95% CI: 0.3969-2.520). All 17 tumors (100%) were microsatellite stable. KRAS testing identified 12 (72%) wild-type tumors and 5 (28%) codon 12 or 13 mutant tumors with identical KRAS point mutations before and after treatment. The identified MSI and KRAS mutational prevalences parallel those reported in the rectal cancer literature. Neoadjuvant therapy did not alter KRAS codon 12 or 13 or MSI results in rectal adenocarcinoma, providing evidence that either pretreatment biopsy or posttreatment resection tissues are appropriate for testing.

The effect of neoadjuvant chemoradiation therapy on the prognostic value of lymph nodes after rectal cancer surgery

Background Neoadjuvant therapy may affect the prognostic impact of total lymph node harvests and lymph node positivity after surgery for rectal cancer. Methods We performed a retrospective review of 390 consecutive patients with histologically confirmed rectal cancer. Postoperative follow-up evaluation and survival were confirmed via medical record review. The impacts of lymph node positivity and total lymph node harvest on survival and recurrence are reflected as proportional hazard ratios (HRs). Results A total of 221 patients underwent neoadjuvant therapy, of whom 75 had positive nodes. Node-positive patients showed a significantly shorter survival time (HR, 2.89; P = .002) and time to local recurrence (HR, 6.36; P = .031) compared with patients without positive nodes. Survival and recurrence were not significantly different between patients with a total harvest of fewer than 12 nodes and patients with a higher lymph node harvest. Conclusions After neoadjuvant treatment and total mesorectal excision, lymph node positivity is associated with significantly shorter survival and time to local recurrence in rectal cancer patients, whereas absolute total lymph node harvests likely have little impact on prognosis.

Analysis of patients with complete histopathological tumour regression after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Background: Our aim was to present the effect of the neoadjuvant chemoradiation therapy on the development of the complete histopathological tumour regression in patients with locally advanced rectal cancer and its influence on a five-year survival of these patients. Methods: In total, 223 patients were included in the analysis; 109 patients had the locally advanced rectal cancer; 75 patients received the neoadjuvant chemoradiation therapy, which was later followed by surgery; 34 patients were treated with the surgery alone. The surgical procedure was done 6 to 8 weeks after the chemoradiation therapy and it was preceded by haematology and biochemical analyses. In addition, patients were examined by ultrasound and MRI imaging of liver to evaluate the effects of neoadjuvant chemoradiation therapy. Accordingly, we had two patient groups: patients with the complete histopathological tumour regression and patients with the incomplete or no regression. We performed the statistical analysis of all locally advanced rectal cancer patients and determined their survival. Results: The complete histopathological tumour regression was found in 10.7% of 75 patients who were treated with preoperative chemoradiation. The down staging of the tumour appeared in 53.3% of patients. There were no stage changes in 21.3% of patients. The disease progressed into a more severe stage in 9.3% of patients, while the effects of the preoperative chemoradiation therapy could not be determined in 5.3% of patients. The survival of patients with the complete histopathological tumour regression was 70% in a five-year period, while it was 40% in patients with incomplete histopathological regression. Conclusion: The preoperative chemoradiation therapy leads to complete histopathological tumour regression and increases a five-year survival (70%). It also leads to the increase of the number of patients who undergo radical surgery.

Aggressive surgical resection after neoadjuvant chemoradiation therapy for locally advanced intrahepatic cholangiocarcinoma.

The poor prognosis of patients with intrahepatic cholangiocarcinoma (ICC) or hilar cholangiocarcinoma is well known. Herein, we described the first reported case of severe locally advanced ICC in which radical surgery was successfully achieved based on the marked effect of neoadjuvant chemoradiation therapy (NCRT) using gemcitabine. A 54-year-old man was admitted to our institution with obstructive jaundice. Abdominal computed tomography (CT) showed a large low-density mass in the caudate lobe, extensively involving the inferior vena cava and main portal vein. Moreover, nodal involvements of the hepatoduodenal ligament were detected concurrently. We therefore regarded this tumor as a severe locally advanced ICC and attempted to initiate combined treatment with gemcitabine (800mg/m(2) biweekly) and three-dimensional conformation radiation (45Gy/25days). After completion of NCRT, this patient underwent a left trisegmentectomy with combined resection of the portal vein and inferior vena cava. Postoperative microscopic findings surprisingly revealed that more than 90% of tumor cells had disappeared with extensive fibrosis, achieving tumor downstaging and tumor volume reduction which were related to the radical resection. In conclusion, ICC showed a favorable histological response to chemoradiation therapy using gemcitabine. Further studies are needed to conclusively assess the effect of NCRT on locally advanced ICC.

Oncologic Result as According to Tumor Regression Grade after Neoadjuvant Chemoradiation Therapy in Locally Advanced Rectal Cancer

Purpose: The effects of neoadjuvant chemoradiation therapy (NCRT) in cases of locally advanced rectal cancer include tumor downstaging with respect to a curative resection and a decreasing incidence of local recurrence. The aim of this study is to evaluate the oncologic results according to the tumor regression grade (TRG) after NCRT and radical surgical resection in cases of locally advanced rectal cancer. Methods: From 1999 to 2003, 140 consecutive patients, who suffered from locally advanced rectal cancer (T3 or T4, or lymph node positive) were enrolled in this study. They all received neoadjuvant chemoradiation therapy and a radical resection. Chemotherapy was based on 5-fluorouracil (5-FU), and the total radiation dose was 5,040 cGy over 6 weeks. A radical surgical resection, including a total mesorectal excision, was done 6 to 8 weeks after the completion of NCRT. We classified patients into subgroups by using the TRG; then, we investigated the overall and the disease-free survival rates and the local recurrence and the distant metastasis rates. Results: One hundred twenty-six (126, 90%) patients responded to radiation therapy. According to the TRG, the numbers of nonresponders (Grade I, NR), partial responders (Grade II, PR), and patients who went into complete remission (Grade III, CR) were 14 (10%), 98 (70%), and 28 (20%), respectively. The overall survival (OS) and the disease-free survival (DFS) rates for 3 years (n=140) were 91.43% and 74.29%, and the rates for 5 years (n=117) were 81.20% and 67.52%, respectively. While there was no significant difference in the 3-year OS or DFS between the three groups stratified by TRG (P=0.1136, P=0.1215), the 5-year OS and DFS showed a statistical difference (P=0.0485, P=0.0458). Furthermore, the 3-year OS and DFS rates (P=0.0451, P=0.0458), as well as the 5-year OS and DFS rates (P=0.0139, P=0.0131) were significantly better for patients in the CR group than for the other patients. Still, no statistical significance differences existed between the CR group and the non-CR groups or between the TRG groups in terms of the local recurrence and the distant metastasis rates (P=0.447, P=0.271). Conclusions: Any tumor response group that shows complete Rremission after NCRT and radical surgical resection has an oncologic benefit in overall survival and disease- free survival in our study.

Radiochemotherapy and Transplantation Allow Long‐Term Survival For Nonresectable Hilar Cholangiocarcinoma

Results of liver transplantation in the treatment of cholangiocarcinoma have been poor as a result of the high incidence of locoregional dissemination and tumor recurrence. This study evaluates the effect of neoadjuvant chemoradiation therapy combined with orthotopic liver transplantation in a carefully selected group of patients with hilar cholangiocarcinoma. Seventeen patients were included in the study. The neoadjuvant protocol included 6,000 cgy biliary brachy-therapy delivered through percutaneous transhepatic catheters and intravenous infusion of 5-fluorouracil (300mg/m2/day) until transplantation. Five of the 17 patients demonstrated tumor progression precluding transplantation. One patient died of sepsis on the waiting list. Eleven patients underwent liver transplantation, a median of 3.4 months (range = 1-26 months) after diagnosis. Five of the 11 (45%) are alive without evidence of tumor recurrence with a median follow up of 7.5 years (range = 2.8-14.5 years). Six deaths occurred in the transplanted patients. Tumor recurrence was responsible for two deaths at 10 and 18months, respectively, after transplantation. Three mortalities resulted from bacterial or fungal peritonitis and sepsis. One patient underwent re-transplantation for chronic rejection and died from graft failure resulting from hepatic artery thrombosis 16 months after diagnosis without evidence of tumor recurrence. Complications of transhepatic catheter placement included bile duct perforation (n = 4) and biliary-portal vein fistula (n = 1). All these patients died of tumor recurrence or sepsis. Cholangiocarcinoma should not be considered an absolute exclusion criteria for orthotopic liver transplantation. Long-term, tumor-free survival was achieved in 45% of the transplanted patients. Complications of biliary catheter placement for brachytherapy were associated with poor outcome.