Search

Background: There is a lack of studies regarding radiotherapy (RT) in patients with gallbladder cancer (GBC) on the survival benefit after surgery and nonsurgical treatment. Therefore, this study evaluated the impact of external beam RT on the overall survival (OS) of patients with GBC in a real-world setting., Methods: Patients with GBC enrolled from the Surveillance, Epidemiology, and End Results (SEER) database were examined through Kaplan-Meier survival curves and multivariable Cox regression analyses., Results: A total of 7,866 patients with GBC were screened for the current analysis, of whom 2,130 (27.1%) did not undergo RT or surgery, 209 (2.7%) underwent RT, 4,511 (57.3%) underwent surgery, and 1,016 (12.9%) underwent both RT and surgery. The median OS times were 4 months, 8 months, 16 months, and 22 months ( p < 0.0001). OS was significantly different between adjuvant RT ( p = 0.0002) and palliative RT ( p < 0.0001). Multifactorial analysis (controlling for age, sex, year of diagnosis, marital status, race, grade, and stage) showed that both adjuvant RT (surgery and adjuvant RT vs. surgery alone; HR, 0.75; 95% CI, 0.69-0.82, p < 0.001) and palliative RT (RT alone vs. no treatment; HR, 0.80; 95% CI, 0.69-0.92, p = 0.003) had a significant impact on patient OS. The results remained stable following sensitivity analyses., Conclusion: The study results indicate that adjuvant and palliative radiation treatment was associated with a survival benefit. GBC patients can derive a survival benefit from external beam RT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Song, Kang, Di, Ren and Wang.)

Introduction: Chemotherapy (CT) is the standard of care in advanced gallbladder cancer (GBC). Should locally advanced GBC (LA-GBC) with response to CT and good performance status (PS) be offered as consolidation chemoradiation (cCTRT) to delay progression and improve survival? There is a scarcity of literature on this approach in the English literature. We present our experience with this approach in LA-GBC., Materials and Methods: After obtaining ethics approval, we reviewed the records of consecutive GBC patients from 2014 to 2016. Out of 550 patients, 145 were LA-GBC who were initiated on chemotherapy. A contrast-enhanced computed tomography (CECT) abdomen was done to evaluate the response to treatment, according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. All responders to CT (PR and SD) with good PS but unresectable were treated with cCTRT. Radiotherapy was given to GB bed, periportal, common hepatic, coeliac, superior mesenteric, and para-aortic lymph nodes up to a dose of 45 to 54 Gy in 25 to 28 fractions along with concurrent capecitabine at the rate of 1,250 mg/m 2 . Treatment toxicity, overall survival (OS), and factors affecting OS were computed based on Kaplan-Meier and Cox regression analysis., Results: ">The median age of patients was 50 years (interquartile range [IQR] = 43-56 years), and men to women ratio was 1:3. A total of 65% and 35% patients received CT and CT followed by cCTRT, respectively. The incidence of Grade 3 gastritis and diarrhea was 10% and 5%, respectively. Responses were partial response (PR; 65%), stable disease (SD; 12%), progressive disease (PD; 10%), and nonevaluable (NE; 13%) because they did not complete six cycles of CT or were lost to follow-up. Among PR, 10 patients underwent radical surgery (six after CT and four after cCTRT). At a median follow-up of 8 months, the median OS was 7 months with CT and 14 months with cCTRT (P = 0.04). The median OS was 57 months, 12 months, 7 months, and 5 months for complete response (CR) (resected), PR/SD, PD, and NE (P = 0.008), respectively. OS was 10 months and 5 months for Karnofsky performance status (KPS) >80 and <80 (P = 0.008), respectively. PS (hazard ratio [HR] = 0.5), stage (HR = 0.41), and response to treatment (HR = 0.05) were retained as independent prognostic factors., Conclusions: CT followed by cCTRT appears to improve survival in responders with good PS.

Background: Gallbladder cancer (GBC) is an uncommon malignancy with high recurrent rate and poor prognosis. This study investigates the recurrent patterns of postoperative GBC, with the aim to guide the adjuvant treatments, including the radiotherapy., Methods: Retrospectively analyzed the 109 GBC patients who underwent surgery in our institution from January 2013 to 2018. Clinical follow-up revealed 54 recurrent cases, of which 40 had detailed locations of recurrence. The sites of recurrence were recorded and divided into the tumor bed, corresponding lymphatic drainage area, intrahepatic recurrence, and the other distant metastasis., Results: The median follow-up time is 34 months (IQR: 11-64). The median disease-free survival (DFS) and overall survival (OS) were 48.8 months and 53.7 months, respectively. Through univariate analysis, risk factors for DFS and OS include tumor markers (CA199 and CEA), hepatic invasion, perineural invasion, lymphovascular invasion, TNM staging and tumor differentiation. Through multivariate analysis, risk factors for DFS include hepatic invasion and TNM staging, and for OS is TNM staging only. Of the 40 cases with specific recurrent sites, 29 patients (29/40, 72.5%) had recurrence in the potential target volume of postoperative radiotherapy (PORT), which include tumor bed and corresponding lymphatic drainage area. The common recurrent lymph node groups included abdominal para-aortic lymph node (No.16, 15/29), hepatoduodenal ligament lymph node (No.12, 8/29), retro-pancreatic head lymph node (No.13, 7/29) and celiac axis lymph node (No.9, 4/29). Twenty cases with recurrences inside the potential PORT target volume were accompanied by distant metastasis. Another 11 cases had distant metastasis alone, so totally 31 cases developed distant metastasis (31/40, 77.5%), including 18 cases with hepatic metastasis., Conclusion: The recurrence and metastasis rates are high in GBC and adjuvant therapy is needed. Up to 75% of the recurrent cases occurred in the potential target volume of postoperative radiotherapy, suggesting that postoperative radiotherapy has the possible value of improving local-regional control. The potential target volume of radiotherapy should include the tumor bed, No.8, No.9, No.11, No.12, No.13, No.14, No. 16a2, No. 16b1 lymph node groups., (© 2022. The Author(s).)

Background and Purpose: The benefits of adjuvant radiotherapy (ART) in gallbladder cancer (GBC) treatment remain inconclusive owing to the rarity of GBC and lack of randomized studies., Methods: PubMed, Medline, Embase, and Cochrane Library were systematically searched until March 2021. The primary endpoint was overall survival (OS). Comparative clinical studies that reported survival outcomes in GBC patients treated with or without ART were included. The comparability of each study was assessed by considering all possible clinical indicators (group 2: ART arm with poor clinical profile; group 1: ART arm with statistically similar profile or no evidence of having inferior clinical factors compared to non-ART arm)., Results: Twenty-one studies involving 6876 GBC patients were reviewed. In pooled analyses of OS, the odds ratio (OR) was 1.26 (p = 0.111) neither favoring ART or non-ART arms. In subgroup analyses considering comparability, the OR significantly favored the ART arm (1.92, p = 0.008) among comparability group 1 studies, whereas it was 1.03 (p = 0.865) in comparability group 2 studies. The pooled rate of 5-year OS in the ART vs. non-ART arms was 44.9% vs. 20.9% in group 1 and 34.1% vs. 40.0% in group 2. With ART, significant reduction in locoregional recurrence (OR 0.21, p = 0.001) but not in distant metastasis (OR 1.32, p = 0.332) was noted., Conclusion: ART not only showed benefits in patients with a similar clinical profile to those treated without ART but also yielded comparable survival in patients with an inferior clinical profile. Our results suggest the more active application of ART in GBC treatment., Protocol Registration: This study is registered in PROSPERO (CRD42021240624, available at: https://www.crd.york.ac.uk/ )., (© 2022. Asian Pacific Association for the Study of the Liver.)

Background: For nonmetastatic locally advanced gallbladder cancer (LAGBC) which remains unresectable and nonmetastatic after chemotherapy, there is no consensus on whether to continue chemotherapy or add local radiotherapy (RT) for improving outcomes., Materials and Methods: Forty-five patients of surgically unresectable nonmetastatic LAGBC were analyzed. Twenty patients did not receive RT (no RT cohort) and received only chemotherapy, while 25 patients received RT (RT cohort) with conformal techniques along with concurrent gemcitabine-based chemotherapy. No RT and RT cohorts were compared for disease-related outcomes and toxicities., Results: Median follow-up of the entire cohort was 11.5 months. Two-year progression-free survival (18.6% vs. 0%, P = 0.0001) and overall survival (37.3% vs. 5%, P = 0.0001) were significantly better in the RT cohort as compared to a no RT cohort. More number of patients had locoregional progression in the no RT cohort (85% vs. 32%, P = 0.0002). Radiation-induced acute and late gastrointestinal toxicity ≥ RTOG Grade 3 were seen in one and two patients, respectively., Conclusion: Addition of local RT to chemotherapy improves the survival outcomes and can be considered as a definite treatment modality for nonmetastatic LAGBC patients not amenable to surgery who have responded to chemotherapy., Competing Interests: None

Nuclear factor kappa B (NF-κB) is a transcriptional factor that can be activated by radiotherapy and chemotherapy. The synthetic protease inhibitor nafamostat mesilate (NM) inhibits NF-κB activity and exerts antitumor actions in various types of cancer. In the present study, we hypothesized that NM might enhance the antitumor action of radiotherapy on gallbladder cancer (GBC) cells by inhibiting radiation-induced NF-κB activity. Thus, we investigated the correlation between radiotherapy and NF-κB activity in GBC cells. We assessed the in vitro effects of radiotherapy with or without NM on NF-κB activity, apoptosis of GBC cells (NOZ and OCUG-1), induction of apoptotic cascade, cell cycle progression, and viability of GBC cells using four treatment groups: 1) radiation (5 Gy) alone; 2) NM (80 μg/mL and 40 μg/mL, respectively) alone; 3) combination (radiation and NM); and 4) vehicle (control). The same experiments were performed in vivo using a xenograft GBC mouse model. In vitro, NM inhibited radiation-induced NF-κB activity. Combination treatment significantly attenuated cell viability and increased cell apoptosis and G2/M phase cell cycle arrest compared with those in the other groups for NOZ and OCUG-1 cells. Moreover, combination treatment upregulated the expression of apoptotic proteins compared with that after the other treatments. In vivo, NM improved the antitumor action of radiation and increased the population of Ki-67-positive cells. Overall, NM enhanced the antitumor action of radiotherapy on GBC cells by suppressing radiation-induced NF-κB activity. Thus, the combination of radiotherapy and NM may be useful for the treatment of locally advanced unresectable GBC., Competing Interests: The authors have declared that no competing interests exist.

Background: The effect of postsurgical radiotherapy (PSRT) among T1-3 gallbladder cancer (GBC) patients with one to three lymph node metastases remains controversial. The aim of this study was to assess the impact of PSRT on gallbladder cancer-specific survival (GBCSS) in patients with stage IIIB., Methods: The data of GBC patients were obtained from the American Surveillance, Epidemiology, and End Results (SEER) Data resources between 2004 and 2015. Then, a 1:1 propensity score matching (PSM) method was performed. GBCSS was compared among all patients. Subgroup analysis was conducted to identify patients who would benefit from PSRT., Results: 726 AJCC (8th edition) stage IIIB GBC patients were included. PSRT failed to improve GBCSS (p = 0.168). Male sex, tumor size ≥ 4 cm and absence of chemotherapy were independent negative prognostic factors. No significant survival benefit from PSRT was found in any subgroup., Conclusions: PSRT provides no survival benefit for IIIB GBC., Competing Interests: Declaration of competing interest We, all the authors listed above, attest that we have no conflicts of interests to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The benefit of adjuvant radiotherapy (ART) for extrahepatic cholangiocarcinoma (EHCC) and gallbladder carcinoma (GBC) is unclear, with conflicting results from nonrandomized studies. We reported a meta-analysis to determine the impact of adjuvant radiotherapy on survival., Methods: PubMed, EMBASE, Cochrane Library and CNKI databases were searched to identify clinical trials of postoperative ART versus no radiotherapy for EHCC and GBC. The obtained data were analyzed using RevMan 5.3 and Stata 14.0 statistical software. Differences between two groups were estimated by calculating the odds ratio (OR) and 95% confidence interval (CI)., Results: A total of 21 clinical trials involving 1465 EHCC and GBC patients were selected according to the inclusion and exclusion criteria and included in this meta-analysis. The meta-analysis showed the following: The 5-year overall survival (OS) rate was higher in the ART group than in the no radiotherapy group (OR = 0.63; 95% CI = 0.50-0.81, p = 0.0002). The 5-year OS rate was significantly higher for those with lymph node-positive disease (OR = 0.15; 95% CI 0.07-0.35; p < 0.00001) and margin-positive disease (OR = 0.40; 95% CI 0.19-0.85; p = 0.02) in the ART group than in the no radiotherapy group. ART had a tendency to bring benefit to the 5-year OS of patients with margin-negative disease but the difference was not statistically significant (OR = 0.57, 95% CI 0.30-1,07, p = 0.08). The local recurrence rate was significantly lower in the ART group than in the no radiotherapy group (OR = 0.54; 95% CI = 0.38-0.76, p = 0.0004), and there was no significant difference in the distant metastasis rate between the two groups (OR = 1.33; 95% CI = 0.95-1.87, p = 0.10)., Conclusions: A meta-analysis of the existing study results showed that compared with no radiotherapy, ART is an effective postoperative treatment for EHCC and GBC.

Background: Osteoradionecrosis (ORN) is a complication that occurs after radiotherapy for head or neck malignancies. ORN of the spine is rare, with only few cases affecting the cervical spine reported to date. To our knowledge, no case of lumbar ORN has been reported. We report a rare case of ORN in the lumbar spine that occurred 2 years after radiotherapy and perform a literature review., Case Presentation: We present a case of lumbar ORN that occurred 2 years after radiotherapy for gallbladder carcinoma. The patient was successfully treated conservatively and followed up for > 10 years., Conclusions: ORN of the spine is a rare complication of radiotherapy. Spinal ORN is clinically described as a chronic disease with a slow onset. The most common presenting symptom of spinal ORN is pain. However, as ORN progresses, spinal kyphosis and instability can lead to neurological compression and thus to induced myelopathy or radiculopathy. Treatment of spinal ORN is comprehensive, including orthosis, medication, hyperbaric oxygen therapy, surgery, and new treatment combinations of pentoxifylline and tocopherol. The surgical rate for spinal ORN is relatively high.

Gallbladder carcinoma is a rare, aggressive biliary tract malignancy, with a 5-year survival of less than 5%. It is the 6th most common gastrointestinal malignancy in the United States and more commonly found in women. While some risk factors include gallstones, porcelain gallbladder, and smoking, gallbladder carcinoma is often found incidentally following cholecystectomy or percutaneous image guided biopsy. Patients frequently present in a late disease state when they are no longer surgical candidates and minimally invasive image guided-interventions therefore play a critical role in the management and treatment of these patients. This review will discuss some of the key procedures and roles interventional radiologists play in the diagnosis and management of patients suffering from gallbladder carcinoma including tissue sampling, placement of intra-arterial infusion pumps, preoperative portal vein embolization (PVE), biliary drainage, management of post-operative complications such as bile leaks or biliary obstruction, and management of chronic pain.

Locally advanced gallbladder cancer poor prognosis due to a high distant metastatic rate and poor overall disease control. The impact of standard therapeutic options is unfortunately modest. Due to the rarity of the disease, evidence-based management continues to evolve. The goal of this review is to highlight the contemporary landscape of radiation therapy for gallbladder cancer. First, the rationale for radiation therapy is described. This includes the risk of locoregional recurrence following resection based on patterns-of-failure data, along with the high locoregional disease burden being a frequent cause morbidity and mortality in unresected cases. Additionally, improvements in systemic therapy over the next decade could shift contemporary patterns of failure more towards proportionally higher locoregional recurrence rates. Second, clinical data of radiation therapy for gallbladder cancer are discussed. These include consideration of postoperative chemoradiotherapy for margin- and/or node-positive cases. Patients with localized unresectable disease could benefit from ablative radiation therapy, based on promising data in non-gallbladder cancer pancreaticobiliary neoplasms. The use of advanced radiation therapy technologies such as proton beam therapy, as a means to deliver ablative radiation therapy in a potentially safer manner, is also mentioned. Lastly, the emerging concept of neoadjuvant therapy for gallbladder cancer is also described, in efforts to allow more patients to receive curative resection.

Objectives: To evaluate therapeutic outcomes of intraluminal brachytherapy (ILBT) for malignant obstructive jaundice (MOJ) against stent alone., Methods: The PubMed, EMBASE, Cochrane Library, CNKI, Wan Fang, VIP and ClinicalTrials.gov databases were searched for all relevant comparative studies from the earliest available date up to 1 May 2017. Subgroup analyses were performed according to the type of study design and type of stent., Results: Twelve studies that compared ILBT versus stent alone were eligible. A total of 641 participants with MOJ were included in our meta-analysis. A total of 340 participants were treated with intraluminal brachytherapy (ILBT); the other 301 participants were treated with biliary stent alone (stent group). ILBT was associated with lower risk of stent occlusion (OR 0.19; 95% CI 0.13-0.28; P < 0.00001) and better mean survival (MD = 3.15; 95% CI 2.64-3.66; P < 0.00001) compared with stent alone. However, the two groups were similar in number of complications (OR 0.84; 95% CI 0.45-1.56; P = 0.578), post-treatment reduced level of total bilirubin (TBIL) (MD = 22.71; 95% CI - 7.24-52.65; P = 0.14), post-treatment reduced level of direct bilirubin (DBIL) (MD = - 3.67; 95% CI - 14.09-6.75; P = 0.49), post-treatment reduced level of alanine aminotransferase (ALT) (MD = 21.09; 95% CI - 5.09-47.28; P = 0.11) and post-treatment reduced level of aspartate aminotransferase (AST) (MD = 20.86; 95% CI - 45.86-87.58; P = 0.54)., Conclusions: ILBT was significantly superior to stent alone in terms of stent occlusion and mean survival. Meanwhile, ILBT had comparable outcomes to stent alone in terms of complications and post-treatment reduced levels of TBIL, DBIL, ALT and AST. Therefore, ILBT may be considered a preferable technique for MOJ.

Background: There are no randomized data to guide clinicians treating patients with gallbladder cancer (GBC). Several retrospective studies reported the survival benefits of adjuvant radiotherapy (RT) and chemoradiation (CRT). In this paper, we examine whether these publications have impacted the utilization of adjuvant therapies and whether their survival benefits are evident in a contemporary cohort of patients., Methods: Using the National Cancer Data Base, we identified 5029 patients diagnosed with T1-3N0-1 GBC and treated with surgical resection from 2005 to 2013. We described trends in receipt of adjuvant treatments for three time periods (2005-2007, 2008-2010, 2011-2013) and calculated three-year overall survival (OS) probabilities for 2989 patients treated in 2005-2010. All statistical tests were two-sided., Results: The percentage of patients who received no adjuvant treatments was unchanged from 2005 to 2013. Adjuvant RT decreased from 4.2% to 1.7% ( P  < .001), adjuvant chemotherapy increased from 8.3% to 13.8% ( P  < .001), and adjuvant CRT remained stable at 15.9% ( P  = .98). Adjuvant treatments were associated with improved three-year OS, with adjusted hazard ratio of 0.47 (95% confidence interval [CI] = 0.39 to 0.58) for CRT, 0.77 (95% CI = 0.61 to 0.97) for chemotherapy, and 0.63 (95% CI = 0.44 to 0.92) for RT. Adjuvant CRT was associated with improved survival in all categories, except T1N0, and in patients with negative and positive margins., Conclusion: Over the past decade there was no increase in the utilization of adjuvant therapies in the United States for patients with resected GBC. Adjuvant therapy is associated with statistically significantly improved three-year OS. This analysis should form the basis for current clinical recommendations and support future prospective trials., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background/aim: Primary Non-Hodgkin's lymphoma of the gallbladder (PNHL-GB) is extremely rare and data on clinical characteristics, optimal management and outcomes of these patients are limited to anecdotal reporting. We, therefore, sought to examine these patients using a population-based database., Materials and Methods: Surveillance, epidemiology, and end results (SEER) database was queried between 1973 and 2013., Results: One hundred and six cases with PNHL-GB were identified (mean age=70.5 ±15 years, whites 92%, male: female 1.03:1). The majority of patients had loco-regional disease (61%) and DLBCL histology (33%). Ninenty cases (85%) had undergone surgical resection, 6 (5.6%) received radiotherapy. Median overall survival (OS) of the entire cohort was 41 months with a 5-year survival rate of 40%. Patients receiving adjuvant RT had superior OS compared to surgery alone (140 ±27 vs. 86 ±16 months, respectively) and patients with DLBCL demonstrated lower survival compared to other histologies (13 vs. 53 months, respectively, p=0.034)., Conclusion: Our study presents the largest dataset of PNHL-GB describing clinical features and outcomes of these patients in addition to summarizing the literature., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Gall bladder carcinoma is one of the most common cancers in India. Gall bladder cancer with metastasis to the breast is very rare. Herein we intend to report a case of carcinoma gall bladder with breast metastasis and a short review of the literature., Methods: This report describes an interesting and unusual case of gall bladder carcinoma presenting with breast metastasis., Case Report: A 38-year lady presented with complaints of right abdominal pain. Bilateral breast examination showed 2×2cm palpable lump in the upper outer quadrant of the left breast. Contrast-enhanced CT of the abdomen and pelvis showed circumferential thickening of gall bladder with the loss of fat plane with the adjacent liver parenchyma. Biopsy from the breast lump was reported as metastatic adenocarcinoma compatible with primary in the gall bladder. Whole body PET-CT showed gall bladder mass with abdominal and pelvic nodes with metastasis to liver, left breast, C7 vertebral body and left supra-clavicular node. She was diagnosed to have disseminated carcinoma gall bladder with liver, breast and supraclavicular nodal metastasis. She received palliative chemotherapy with gemcitabine and carboplatin and radiotherapy to C7 vertebra. After receiving 3 cycles of chemotherapy, chemotherapy was changed to the second line with single agent capecitabine. In spite of two lines of chemotherapy, she succumbed to disease progression and expired., Conclusion: There are limited examples of gall bladder adenocarcinoma with simultaneous metastasis to breast in the English literature. Our case showed an unusual dissemination of gall bladder cancer., (Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.)

Purpose: Combination chemotherapy with gemcitabine and cisplatin is a standard treatment for patients with advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of gemcitabine- and cisplatin-based concurrent chemoradiotherapy in patients with unresectable biliary tract cancer., Methods: Patients with pathologically proven, unresectable, non-metastatic biliary tract cancer were enrolled. Gemcitabine was administered intravenously at a dose of 1000 mg/m(2) on days 1, 8, and 15. Cisplatin was administered intravenously at a dose of 70 mg/m(2) on day 1. All the patients underwent concurrent radiotherapy with 45 Gy in 1.8-Gy daily fractions. After treatment completion, tumor response was evaluated by using computed tomography., Results: Eighteen patients were enrolled between June 2007 and October 2011. Their median age was 61 years (range, 38-72 years). Eight patients (44.5 %) were diagnosed with gallbladder cancer, six (33.3 %) with Klatskin's tumor, and four (22.2 %) with distal common bile duct cancer. After treatment completion, partial response was achieved in five patients (27.8 %) and stable disease in 13 patients (72.2 %). The overall response rate was 27.8 %, and the disease stabilization rate was 100 %. No grade 4 adverse events or treatment-related deaths occurred. The most common grade 3 adverse events were thrombocytopenia (33.3 %) and anemia (11.1 %). The median progression-free and overall survival times were 6.8 months (range, 4.5-19.8 months) and 9.6 months (5.4-30.4 months), respectively., Conclusions: This study shows that gemcitabine- and cisplatin-based concurrent chemoradiotherapy is feasible and tolerable in patients with unresectable and non-metastatic biliary tract cancer.

Purpose: The purpose of this study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer (GBC) patients who have undergone R0 resection., Materials and Methods: Clinical data were collected on 441 consecutive patients who underwent R0 resection for stage I-III GBC. Eligible patients were classified into adjuvant therapy and surveillance only groups. Propensity score matching (PSM) between the two groups was performed, adjusting clinical factors., Results: In total, 84 and 279 patients treated with adjuvant therapy and followed up with surveillance only, respectively, were included in the analysis. Before PSM, the 5-year relapse-free survival (RFS) rate was lower in the adjuvant therapy group than in the surveillance only group (50.8% vs. 74.8%, p < 0.001), although there was no statistically significant difference in the 5-year overall survival (OS) rate (66.2% vs. 79.5%, p=0.089). After the PSM, baseline characteristics became comparable and there were no differences in the 5-year RFS (50.8% vs. 64.8%, p=0.319) and OS (66.2% vs. 70.4%, p=0.703) rates between the two groups., Conclusion: The results suggest that fluoropyrimidine-based adjuvant therapy is not indicated in stage I-III GBC patients who have undergone R0 resection., Competing Interests: relevant to this article was not reported.

Gall bladder carcinoma (GBC) is considered the fifth most common one of the most aggressive gastro intestinal tract malignancies. Owing to their large incidence randomised controlled trials have hardly been conducted to look into their optimum treatment. Over the years surgical resection has been considered the only curative treatment of these tumors. However, the outcome still remains guarded. The predominant pattern of failure is loco-regional followed by systemic. Hence, local adjuvant radiation has been used by different institutes with concurrent and adjuvant chemotherapy. The large retrospective series with their limitations showed improved survival in patients with regional spread or tumors infiltrating the liver when treated with adjuvant radiotherapy. In the present era with modern radiation techniques and target delineation radiation may further improve upon the impact without adding to the toxicity profile. Hence, radiation in gall bladder cancer needs a relook to optimize treatment outcome of such aggressive disease., (Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Biliary tract cancer, or cholangiocarcinoma, arises from the biliary epithelium of the small ducts in the periphery of the liver (intrahepatic) and the main ducts of the hilum (extrahepatic), extending into the gallbladder. The incidence and epidemiology of biliary tract cancer are fluid and complex. It is shown that intrahepatic cholangiocarcinoma is on the rise in the Western world, and gallbladder cancer is on the decline. Radiation therapy has emerged as an important component of adjuvant therapy for resected disease and definitive therapy for locally advanced disease. The emerging sophisticated techniques of imaging tumors and conformal dose delivery are expanding the indications for radiotherapy in the management of bile duct tumors. As we understand more about the molecular pathways driving biliary tract cancers, targeted therapies are at the forefront of new therapeutic combinations. Understanding the gene expression profile and mutational burden in biliary tract cancer allows us to better discern the pathogenesis and identify promising new developmental therapeutic targets.

Purpose: The role of adjuvant radiation for gallbladder carcinoma (GBC) is uncertain. We combine the experience of six National Cancer Institute-designated cancer centers to explore the impact of adjuvant radiation following oncologic resection of GBC., Methods: Patients who underwent extended surgery for GBC at Johns Hopkins, Mayo Clinic, Duke University, Oregon Health & Science University, University of Michigan, and University of Texas MD Anderson between 1985 and 2008 were reviewed. Patients with metastatic disease at surgery, gross residual disease, or missing pathologic information were excluded., Results: Of the 112 patients identified, 61 % received adjuvant radiation, 93 % of whom received concurrent chemotherapy. Median follow-up of surviving patients was 47.3 (range 2.2-167.7) months. Patients who received adjuvant radiation had a higher rate of advanced T-stage (57 vs. 16 %, p < 0.01), lymph node involvement (63 vs. 18 %, p < 0.01), and positive microscopic margins (37 vs. 9 %, p < 0.01) compared with patients managed with surgery alone, but overall survival (OS) was comparable between the two cohorts (5-year OS: 49.7 vs. 52.5 %, p = 0.20). Lymph node involvement had the strongest association with poor OS (p < 0.01). Adjuvant radiation was associated with decreased isolated local failure (hazard ratio 0.17, 95 % confidence interval 0.05-0.63, p = 0.01). However, 71 % of recurrences included distant failure., Conclusions: Following oncologic resection for GBC, adjuvant radiation may offer improved local control compared with observation. The benefit of adjuvant radiation beyond chemotherapy alone should therefore be explored. Certainly, the high rate of distant failure highlights the need for more effective systemic therapy.

Purpose: The role of postoperative therapy in extrahepatic cholangiocarcinoma (EHCC) or gallbladder carcinoma (GBCA) is unknown. S0809 was designed to estimate 2-year survival (overall and after R0 or R1 resection), pattern of relapse, and toxicity in patients treated with this adjuvant regimen., Patients and Methods: Eligibility criteria included diagnosis of EHCC or GBCA after radical resection, stage pT2-4 or N+ or positive resection margins, M0, and performance status 0 to 1. Patients received four cycles of gemcitabine (1,000 mg/m(2) intravenously on days 1 and 8) and capecitabine (1,500 mg/m(2) per day on days 1 to 14) every 21 days followed by concurrent capecitabine (1,330 mg/m(2) per day) and radiotherapy (45 Gy to regional lymphatics; 54 to 59.4 Gy to tumor bed). With 80 evaluable patients, results would be promising if 2-year survival 95% CI were > 45% and R0 and R1 survival estimates were ≥ 65% and 45%, respectively., Results: A total of 79 eligible patients (R0, n = 54; R1, n = 25; EHCC, 68%; GBCA, 32%) were treated (86% completed). For all patients, 2-year survival was 65% (95% CI, 53% to 74%); it was 67% and 60% in R0 and R1 patients, respectively. Median overall survival was 35 months (R0, 34 months; R1, 35 months). Local, distant, and combined relapse occurred in 14, 24, and nine patients. Grade 3 and 4 adverse effects were observed in 52% and 11% of patients, respectively. The most common grade 3 to 4 adverse effects were neutropenia (44%), hand-foot syndrome (11%), diarrhea (8%), lymphopenia (8%), and leukopenia (6%). There was one death resulting from GI hemorrhage., Conclusion: This combination was well tolerated, has promising efficacy, and provides clinicians with a well-supported regimen. Our trial establishes the feasibility of conducting national adjuvant trials in EHCC and GBCA and provides baseline data for planning future phase III trials., (© 2014 by American Society of Clinical Oncology.)

It was previously demonstrated that dose delivered by a conventional linear accelerator using IMRT or VMAT can be reconstructed - on patient or phantom datasets - using helical diode array measurements and a technique called planned dose perturbation (PDP). This allows meaningful and intuitive analysis of the agreement between the planned and delivered dose, including direct comparison of the dose-volume histograms. While conceptually similar to modulated arc techniques, helical tomotherapy introduces significant challenges to the PDP formalism, arising primarily from TomoTherapy delivery dynamics. The temporal characteristics of the delivery are of the same order or shorter than the dosimeter's update interval (50 ms). Additionally, the prevalence of often small and complex segments, particularly with the 1 cm Y jaw setting, lead to challenges related to detector spacing. Here, we present and test a novel method of tomotherapy-PDP (TPDP) designed to meet these challenges. One of the novel techniques introduced for TPDP is organization of the subbeams into larger subunits called sectors, which assures more robust synchronization of the measurement and delivery dynamics. Another important change is the optional application of a correction based on ion chamber (IC) measurements in the phantom. The TPDP method was validated by direct comparisons to the IC and an independent, biplanar diode array dosimeter previously evaluated for tomotherapy delivery quality assurance. Nineteen plans with varying complexity were analyzed for the 2.5 cm tomotherapy jaw setting and 18 for the 1 cm opening. The dose differences between the TPDP and IC were 1.0% ± 1.1% and 1.1% ± 1.1%, for 2.5 and 1.0 cm jaw plans, respectively. Gamma analysis agreement rates between TPDP and the independent array were: 99.1%± 1.8% (using 3% global normalization/3 mm criteria) and 93.4% ± 7.1% (using 2% global/2 mm) for the 2.5 cm jaw plans; for 1 cm plans, they were 95.2% ± 6.7% (3% G/3) and 83.8% ± 12% (2% G/2). We conclude that TPDP is capable of volumetric dose reconstruction with acceptable accuracy. However, the challenges of fast tomotherapy delivery dynamics make TPDP less precise than the IMRT/VMAT PDP version, particularly for the 1 cm jaw setting.

Aim: To evaluate the results of postoperative radiotherapy (PORT) and to identify prognostic factors for gallbladder cancer (GBC)., Patients and Methods: We retrospectively analyzed 86 patients with GBC who underwent potentially curative surgical resection and PORT between November 1993 and December 2009. All patients received three-dimensional conformal radiotherapy and 61 patients (71%) had concurrent chemotherapy. Survival outcomes including locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) rates were analyzed., Results: The median follow-up period was 83 months for surviving patients. The 5-year OS, DFS and LRC rates were 42%, 36% and 73%, respectively. Isolated locoregional recurrence as first failure occurred in seven patients (8%). On multivariate analysis, the postoperative carbohydrate antigen 19-9 (CA 19-9) level was a significant prognostic factor for LRC, DFS and OS., Conclusion: Adjuvant radiotherapy might be an effective treatment in terms of LRC in GBC. Postoperative CA 19-9 might be useful as a surrogate marker for survival., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Endoscopic placement of a iodine-125 radioactive stent is useful to treat obstructive jaundice with unresectable periampullary tumors. This study aimed to retrospectively evaluate the obstructive component of biliary radioactive stents and discuss the different obstructive mechanism with common plastic stents., Patients and Methods: Twenty consecutive patients with malignant obstruction underwent insertion of stents into the common bile duct, including 10 radioactive stents and 10 polyethylene stents. The radioactive stents were withdrawn after ∼3 months or earlier if clinical signs suggested stent clogging. Polyethylene stents were withdrawn after physical signs suggested stent clogging. Bacteriologic analyses included identification of aerobic and anaerobic bacteria. Stent surfaces were observed by scanning electron microscopy. Stent deposition was identified by Fourier-transformed infrared spectroscopy and pyrolysis derivatization/gas chromatography/mass spectrometry., Results: Radioactive stent group and polyethylene stent group stents were placed for 86 days (interquartile range 62, 114) and 146 days (interquartile range 105, 181) respectively. The placement duration of the two types of stents was statistically significant. A variety of microorganisms were cultured from the stent deposits. Scanning electron microscope images showed a thicker necrotic layer on the external surface of polyethylene stent than the radioactive stent group. The proportions of obstructive components in each stent were different, but none of them were statistically significant. Necrotic tumor tissue was found in the radioactive stent group., Conclusion: Similar clogging events occurred in both radioactive stents and polyethylene stents. The median duration time of the radioactive stent was shorter, probably because of the smaller inner diameter, and the radioactive seeds exerted no beneficial effect in inhibiting microorganisms.

Background/aims: To investigate the survival outcome of intraoperative radiation therapy for patients with gallbladder cancer on the basis of experience at a single institution., Methodology: The medical records of 8 patients with gallbladder cancer who were treated with intraoperative radiation therapy during surgical resection or palliative surgery were retrospectively analyzed. The primary endpoint was overall survival. The median follow-up time was 20.8 months., Results: The median survival time was 15.0 months. Overall survival for all patients was 75.0% at 1 year, 37.5% at 3 years, and 25.0% at 5 years. Three patients underwent complete resection, and 5 patients had residual tumor after resection or palliative surgery. The 3-year OS rate for 3 patients with no residual tumor after curative resection was 66.7%, with a mean survival time of 122.6 months, whereas the 3-year OS rate for 5 patients with macroscopic residual diseasewas 0% with a mean survival time of 13.5 months (P = 0.014)., Conclusions: The results of the present study suggest that intraoperative radiation therapy with or without external beam radiation therapy was safe and beneficial for patients who underwent curative resection with negative margins and allows the possibility of long-term survival.

Background: We sought to define the utilization and effect of adjuvant external-beam radiotherapy (XRT) on patients having undergone curative-intent resection for gallbladder cancer (GBC)., Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 5,011 patients with GBC who underwent resection between 1988 and 2009. The impact of XRT on survival was analyzed by the use of propensity-score matching by comparing clinicopathologic factors between patients who received resection only versus resection plus XRT., Results: Median age was 72 years, and most patients were female (73.4%); 66.2% patients had intermediate to poorly differentiated tumors, and 19.1% had lymph node metastasis. The majority (75.0%) had "localized" disease by Surveillance, Epidemiology, and End Results classification. A total of 899 patients (17.9%) received XRT whereas 4,112 patients did not. Factors associated with receipt of XRT were younger age (odds ratio [OR] 5.33), tumor extension beyond the serosa (OR 1.55), intermediate- to poorly differentiated tumors (OR 1.56), and lymph node metastasis (OR 2.59) (all P < .05). Median and 1-year survival were 15 months and 59.0%, respectively. On propensity-matched multivariate model, despite having more advanced tumors, XRT was independently associated with better long-term survival at 1 year (hazard ratio 0.45; P < .001), but not 5 years (hazard ratio 1.06; P = .50)., Conclusion: A total of 18% of patients with GBC received XRT after curative intent surgery. The use of adjuvant XRT was associated with a short-term survival benefit, but the benefit dissipated over time., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: To summarize the experiences in gallbladder cancer treatment, evaluate the efficacy of postoperative radiotherapy, and investigate the method of improving the survival of gallbladder cancer patients., Methods: One hundred and twenty-seven gallbladder cancer patients, treated in our center by radical resection (84 cases) and combined with postoperative radiotherapy (43 cases), between June 2003 to December 2009 were included in this study. Their clinical data and follow-up results were retrospectively analyzed. According to AJCC staging criteria, the survival time and 1-, 3- and 5-year survival rates of the surgery group and the postoperative radiotherapy group at the different pathological stages and resection margin status were compared., Results: The median survival time of postoperative radiotherapy patients in stage III was 16.9 months, and the 1-year, 3-year, and 5-year survival rates were 55.7%, 23.5% and 18.2%, respectively, significantly higher than that of the simple operation group ( median survival time 14.3 months, and 1-year, 3-year, 5-year survival rates 42.7%, 22.6% and 16.7%, respectively) (P<0.05). The median survival time of postoperative radiotherapy patients in stage IV, the median survival time was 9.7 months in the postoperative radiotherapy group and 6.3 months in the simple surgery group, and the 1-year survival rates were 14.2% and 9.8%, the 3-year survival rates were 7.2% and 3.9%, the 5-year survival rates were 7.2% and 1.9%, respectively, all showing a statistically significant difference (P<0.05). Among the stage III and IVpatients, all the 1-, 3- and 5-year survival rates of the postoperative radiotherapy group were higher than that of the simple R0 and R1 surgical resection group (all P<0.05), but with a non-significant difference between the stageIandIIpatients (P>0.05). The main side effects in postoperative radiotherapy patients including nausea, vomiting and abdominal pain, all were successfully alleviated by symptomatic and supportive therapy, and the radiotherapy was successfully completed., Conclusions: With regard to the gallbladder cancer patients in stage III and IV, the survival rate can be obviously increased by postoperative radiotherapy. However, for patients in stageIand II, whether postoperative radiotherapy significantly improves the survival or not, needs to be further validated in larger scale studies.

No randomized controlled trials have been conducted in gallbladder cancer to establish standard treatments. We therefore conducted the first Latin American Consensus meeting for the management of gallbladder cancer. In this paper we report the conclusions of the experts' panel for (neo) adjuvant treatment of resectable gallbladder cancer. These are based on the review of the literature, the discussion of the participating experts and the vote of the assistants (surgical oncologists, medical oncologists, radiation oncologists and others). The reviewed topics were the role or adjuvant radiochemotherapy in T1 bN0M0, T2-3 N0-1M0 and T4 N0-1 M0 disease and doses, schedules and drugs for radiochemotherapy.

Background/aims: The aim of our study was to evaluate preliminary results of intensity modulated radiotherapy (IMRT) in patients with inoperable subhepatic tumors., Methodology: Thirteen patients with inoperable cholangiocarcinoma or gall bladder carcinoma were treated by biliary drainage and intensity modulated radiotherapy. In patients with tumors limited to the biliary duct only tumor stenosis was irradiated to the dose of 50-60 Gy. In patients with bulky extraductal tumors the dose was 50 Gy/25 fractions to the whole tumor and an integrated boost was used to raise the dose to the malignant stenosis to 60 Gy/25 fractions., Results: Doses to organs at risk (duodenum, small intestine, liver) were in tolerable limits. In four patients transient fever occurred; one patient had duodenal bleeding that resolved after conservative treatment. Recurrent dilatation of the biliary tract was observed in 4 patients and was managed by exchange of the internal biliary drainage. Median survival was 10.4 months, 5 patients survived for more than one year following diagnosis., Conclusions: IMRT of inoperable extrahepatic biliary tract tumors allows application of high doses of radiation to the tumor with effective sparing of healthy tissues. The control of jaundice is good. In selected cases IMRT may prolong overall survival.

Aim: To assess the efficacy and toxicity of conformal radiotherapy (CRT) and compare with intensity-modulated radiotherapy (IMRT) in the treatment of gallbladder cancer., Methods: Between November 2003 and January 2010, 20 patients with gallbladder cancer were treated with CRT with or without chemotherapy after surgical resection. Preliminary survival data were collected and examined using both Kaplan-Meier and actuarial analysis. Demographic and treatment parameters were collected. All patients were planned to receive 46-56 Gy in 1.8 or 2.0 Gy per fraction. CRT planning was compared with IMRT., Results: The most common reported acute toxicities requiring medication (Radiation Therapy Oncology Group, Radiation Therapy Oncology Group Grade 2) were nausea (10/20 patients) and diarrhea (3/20). There were no treatment-related deaths. Compared with CRT planning, IMRT significantly reduced the volume of right kidney receiving > 20 Gy and the volume of liver receiving > 30 Gy. IMRT has a negligible impact on the volume of left kidney receiving > 20 Gy. The 95% of prescribed dose for a planning tumor volume using either 3D CRT or IMRT planning were 84.0% ± 6.7%, 82.9% ± 6.1%, respectively (P > 0.05)., Conclusion: IMRT achieves similar excellent target coverage as compared with CRT planning, while reducing the mean liver dose and volume above threshold dose. IMRT offers better sparing of the right kidney compared with CRT planning, with a significantly lower mean dose and volume above threshold dose.

Background: Gastrointestinal cancers, especially pancreatobiliary cancers, are frequently associated with or are complicated by thromboembolic phenomena due to hypercoagulability and/or altered venous drainage, especially of the abdomen and lower limbs. This report describes an unusual and interesting case of gallbladder carcinoma developing a viable tumor thrombus in the superior vena cava (SVC) with resultant SVC obstruction, while on gefitinib-based anti-epidermal growth factor receptor (EGFR) therapy., Methods: A 60-year-old woman was incidentally diagnosed to have gallbladder cancer on cholecystectomy. She had disease recurrence and received systemic chemotherapy followed by gefitinib-based anti-EGFR therapy. Subsequently, while on gefitinib-based therapy, she presented with clinical signs and symptoms suggestive of SVC thrombosis., Results: A whole body PET scan revealed a metabolically active tumor thrombus in the SVC, besides other sites of metabolically active disease inclusive of the lung parenchyma, lymph nodes and abdomen. She was treated with anti-thrombotics and external beam radiotherapy directed to the SVC thrombus leading to symptomatic relief. She continues to survive on the day of writing this report., Conclusions: This rare complication, though theoretically possible, is unreported because of the short overall survival of advanced gallbladder cancer patients. This highlights that with the availability of better chemotherapeutic/biotherapeutic agents for increasing in the lifespan of cancer patients, we may come across such cases more frequently in the future.

Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma., Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated., Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. On univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004)., Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.

Purpose: Biliary tract lesions are comparatively rare neoplasms, with ambiguous indications for radiotherapy. The specific aim of this study was to report the clinical results of a single-institution biliary tract series treated with modern radiotherapeutic techniques, and detail results using both conventional and image-guided intensity-modulated radiation therapy (IG-IMRT)., Methods and Materials: From 2001 to 2005, 24 patients with primary adenocarcinoma of the biliary tract (gallbladder and extrahepatic bile ducts) were treated by IG-IMRT. To compare outcomes, data from a sequential series of 24 patients treated between 1995 and 2005 with conventional radiotherapy (CRT) techniques were collected as a comparator set. Demographic and treatment parameters were collected. Endpoints analyzed included treatment-related acute toxicity and survival., Results: Median estimated survival for all patients completing treatment was 13.9 months. A statistically significant higher mean dose was given to patients receiving IG-IMRT compared to CRT, 59 vs. 48Gy. IG-IMRT and CRT cohorts had a median survival of 17.6 and 9.0 months, respectively. Surgical resection was associated with improved survival. Two patients (4%) experienced an RTOG acute toxicity score>2. The most commonly reported GI toxicities (RTOG Grade 2) were nausea or diarrhea requiring oral medication, experienced by 46% of patients., Conclusion: This series presents the first clinical outcomes of biliary tract cancers treated with IG-IMRT. In comparison to a cohort of patients treated by conventional radiation techniques, IG-IMRT was feasible for biliary tract tumors, warranting further investigation in prospective clinical trials.

The role of post-operative radiotherapy (PORT) is still controversial for some cancer sites. In the absence of large randomized controlled trials, survival prediction models can help estimate the predicted benefit of PORT for specific settings. The purpose of this study was to compare the performance of two types of prediction models for estimating the benefit of PORT for 2 cancer sites. Using data from the Surveillance, Epidemiology, and End Results database, we constructed prediction models for gallbladder (GB) cancer and non-small cell lung cancer (NSMLC), using Cox proportional hazards and Random Survival Forests. We compared validation measures for discrimination and found that both the CPH and RSF models had comparable C-indices. For GB cancer, PORT was associated with improved survival for node positive patients, and for NSCLC, PORT was associated with a survival benefit for patients with N2 disease.

Purpose: The benefit of adjuvant radiotherapy (RT) for gallbladder cancer remains controversial because most published data are from small, single-institution studies. The purpose of this study was to construct a survival prediction model to enable individualized predictions of the net survival benefit of adjuvant RT for gallbladder cancer patients based on specific tumor and patient characteristics., Methods: A multivariate Cox proportional hazards model was constructed using data from 4,180 patients with resected gallbladder cancer diagnosed from 1988 to 2003 from the Surveillance, Epidemiology, and End Results database. Patient and tumor characteristics were included as covariates and assessed for association with overall survival (OS) with and without adjuvant RT. The model was internally validated for discrimination and calibration using bootstrap resampling., Results: On multivariate regression analysis, the model showed that age, sex, papillary histology, stage, and adjuvant RT were significant predictors of OS. The survival prediction model demonstrated good calibration and discrimination, with a bootstrap-corrected concordance index of 0.71. The model predicts that adjuvant RT provides a survival benefit in node-positive or >or= T2 disease. A nomogram and a browser-based software tool were built from the model that can calculate individualized estimates of predicted net survival gain attributable to adjuvant RT, given specific input parameters., Conclusion: In the absence of large, prospective, randomized, clinical trial data, a regression model can be used to make individualized predictions of the expected survival improvement from the addition of adjuvant RT after gallbladder cancer resection.

Gallbladder cancer is a disease with poor prognosis, especially when it is associated with distant metastasis. Here we report a rare case of a patient with gallbladder cancer with extensive local and distant lymph node metastases and multiple liver metastases who has survived for more than 13 years through aggressive treatments. A 54-year-old woman developed right upper quadrant pain. Computed tomography (CT) revealed a papillary tumor in the gallbladder. Low-density tumors in segments 4, 5, and 8 of the liver and extensive paraaortic lymph node swelling were observed. She underwent central hepatic bisectionectomy and paraaortic lymphadenectomy. Two months later, hepatic metastases were found in segments 2, 3, 6, and 7, and percutaneous ethanol injection and transcatheter arterial chemoembolization were performed. Twelve months after the first surgery, CT revealed lymph node swelling around the right external iliac artery and behind the left renal vein. Metastatic lymph node dissection and resection and reconstruction of the right external iliac artery and vein with artificial graft replacements were performed. Two months later, CT revealed a paraesophageal lymph node swelling, which was treated by radiotherapy. At present, 13 years after the first surgery, and 11 years after the last radiotherapy, she is alive without any sign of recurrence.

Background: Gallbladder carcinoma is a rare malignancy and is associated with dismal outcomes. The aim of this study was to better define the role of adjuvant radiation therapy in the management of gallbladder carcinoma., Methods: The Surveillance, Epidemiological, and End Results (SEER) survey from the National Cancer Institute was queried from 1992 to 2002. Retrospective analysis was done. The end-point of the study was overall survival., Results: There were a total of 3,187 cases of gallbladder carcinoma in the registry from 1992 to 2002. Of the surgical group, 35% were stage I, 36% were stage II, 6% were stage III, and 21% were stage IV. Adjuvant radiation was used in 17% of the cases. The median survival for those patients receiving adjuvant radiation therapy was 14 months compared to an 8 months median survival for those treated without adjuvant radiation therapy (P < or = 0.001). The survival benefit associated with radiation use was only presenting those patients with regional spread (P = 0.0001) and tumors infiltrating the liver (P = 0.011)., Conclusion: The use of adjuvant radiation therapy is associated with improved survival in patients with locally advanced gallbladder cancer or gallbladder cancer with regional disease., (Copyright 2007 Wiley-Liss, Inc.)

Purpose: The role of radiation therapy (RT) in extrahepatic cholangiocarcinoma (EHCC) is not clear and only limited reports exist on the use of this modality. We have reviewed our institutional experience to determine the pattern of failure in patients after potentially curative resection and the expected outcomes after adjuvant RT and in unresectable patients., Methods and Materials: After institutional review board approval, 81 patients diagnosed with EHCC (gallbladder 28, distal bile duct 24, hilar 29) between June 1986 and December 2004 were identified and their records reviewed. Twenty-eight patients (35%) underwent potentially curative resection with R0/R1 margins. Fifty-two patients (64%) were unresectable or underwent resection with macroscopic residual disease (R2). All patients received three-dimensional planned megavoltage RT. The dose for each patient was converted to the equivalent total dose in a 2 Gy/fraction, using the linear-quadratic formalism and alpha/beta ratio of 10. The median dose delivered was 58.4 Gy (range, 23-88.2 Gy). 54% received concomitant chemotherapy., Results: With a median follow-up time of 1.2 years (range, 0.1-9.8 years) 75 patients (93%) have died. Median overall survival (OS) and progression-free survival (PFS) were 14.7 (95% CI, 13.1-16.3) and 11 (95% CI, 7.6-13.2) months, respectively. There was no difference among the three disease sites in OS (p = 0.70) or PFS (p = 0.80). Complete resection (R0) was the only predictive factor significantly associated with increase in both OS and PFS (p = 0.002), and there was no difference in outcomes between R1 and R2 resections. The first site of failure was predominantly locoregional (68.8% of all failures)., Conclusion: Local failure is a major problem in EHCC, suggesting the need for more intense radiation schedules and better radiosensitizing strategies. Because R1 resection appears to convey no benefit, it appears that surgery should be contemplated only when an R0 resection is likely. Borderline-resectable patients might be better served by neoadjuvant therapy.

Purpose: Clinical and technical parameter analysis of patients treated with ultrasound-based image-guided tomotherapeutic IMRT for gallbladder cancer., Methods and Materials: Between 8/2001 and 5/2005, 10 patients with primary tumors of the gallbladder were treated by image-guided IMRT to median doses of 59 Gy. To analyze normal tissue radiation exposure reduction using this novel approach, a virtual plan comparison between actually delivered IMRT plans and re-computed plans with identical inverse planning parameters but more conventional PTV safety margins was conducted., Results: Average CTV was 379 cm(3), with a mean initial PTV of 834 cm(3). In 9/10 patients, a boost was delivered to a mean CTV(boost) of 171 cm(3) and average PTV(boost) of 241 cm(3). One patient reported RTOG grade 3 acute toxicity. All other patients exhibited Grade 2 or lower acute toxicity. Preliminary median overall survival was 16.7 months (range 3.2-34.9 months), with 5/10 patients alive at analysis. Virtual plan comparison revealed significant organ-at-risk sparing by the enabled PTV margin reduction., Conclusion: Ultrasound-based image-guided IMRT is a feasible mechanism of delivering conformal radiation doses to tumors of the gallbladder with acceptable toxicity. Early outcome data with this novel radiation planning and delivery technique are encouraging and comparable to previously reported literature.

Purpose: To evaluate geometric shifting of the porta hepatis induced by liver regeneration during radiotherapy (RT) after partial hepatectomy for biliary tract cancer., Methods and Materials: Between August 2004 and August 2005, the study enrolled 10 biliary tract cancer patients who underwent hemihepatectomy or more extensive surgery and were scheduled to receive postoperative RT. All patients received 4500 cGy RT in 25 fractions with concurrent 5-fluorouracil. Before RT and in the third and fifth weeks during RT, the liver volume was determined using CT, and geometric location of the porta hepatis was determined using a conventional simulator., Results: The liver volume increase during RT was 246.6 +/- 118.2 cm(3). The overall actual shifting length of the porta hepatis was 9.8 +/- 2.5 mm, with right and left hepatectomy causing a 10.1 +/- 1.7 mm shift to the right or 9.2 +/- 4.3 mm shift to the left, respectively. The actual shifting length of the porta hepatis was proportional to the increase in liver volume during RT (r = 0.742, p = 0.014)., Conclusion: The results of this study have demonstrated that the porta hepatis can be shifted by liver regeneration after partial hepatectomy. We recommend an additional RT margin or adaptive RT (repeat planning at several intervals during the treatment course) to avoid exclusion of the porta hepatis from the RT target volume after partial hepatectomy for biliary tract cancer.

Gallbladder cancer (GC) is considered a rare disease associated with a poor prognosis. Unfortunately, the low number of cases makes the performance of trials addressing the role of adjuvant, neoadjuvant, and/or palliative therapy difficult. For a long time, the majority of trials were 5-fluorouracil (5 FU)-based, and results were uniformly poor. Since the introduction of Gemcitabine, response rates of approximately 30% have been observed through the use of this drug and new approaches have been tested. In this sense, drugs such as Cisplatin and Capecitabine have been employed concurrently with gemcitabine and/or radiation. Since a recurrence pattern is both distant and local, chernoradiation seems a logical option to deal with the disease. However, at the present time, the lack of valid and scientific evidence means that most of the recommendations originate from trials dealing with other tumors, such as pancreas cancer and biliary tract cancer (BTC). The aforementioned treatment alternatives warrant further evaluation focusing on GC., (Copyright 2006 Wiley-Liss, Inc.)