Outcomes of stereotactic body radiotherapy for unresectable primary or recurrent cholangiocarcinoma.
30 Sep 2014-Radiation oncology journal (Korean Society for Therapeutic Radiology and Oncology)-Vol. 32, Iss: 3, pp 163-169
TL;DR: SBRT can be considered as an effective local modality for unresectable primary or recurrent cholangiocarcinoma and showed statistically significant higher overall survival rate in the recurrent tumor group.
Abstract: PURPOSE To report the results of stereotactic body radiotherapy (SBRT) for unresectable primary or recurrent cholangiocarcinoma. MATERIALS AND METHODS From January 2005 through August 2013, 58 patients with unresectable primary (n = 28) or recurrent (n = 30) cholangiocarcinoma treated by SBRT were retrospectively analyzed. The median prescribed dose was 45 Gy in 3 fractions (range, 15 to 60 Gy in 1-5 fractions). Patients were treated by SBRT only (n = 53) or EBRT + SBRT boost (n = 5). The median tumor volume was 40 mL (range, 5 to 1,287 mL). RESULTS The median follow-up duration was 10 months (range, 1 to 97 months). The 1-year, 2-year overall survival rates, and median survival were 45%, 20%, and 10 months, respectively. The median survival for primary group and recurrent group were 5 and 13 months, respectively. Local control rate at 1-year and 2-year were 85% and 72%, respectively. Disease progression-free survival rates at 1-year and 2-year were 26% and 23%, respectively. In univariate analysis, ECOG performance score (0-1 vs. 2-3), treatment volume ( 12 months interval from surgery to recurrence showed statistically significant higher overall survival rate than those with ≤12 months (p = 0.026). Six patients (10%) experienced ≥grade 3 complications. CONCLUSION SBRT can be considered as an effective local modality for unresectable primary or recurrent cholangiocarcinoma.
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TL;DR: The current review focuses on recent advances in the diagnosis and treatment of patients with cholangiocarcinoma and, in particular, on the role of endoscopy, surgery, transplantation, radiotherapy, systemic therapy, and liver‐directed therapies in the curative or palliative treatment of these individuals.
Abstract: Cholangiocarcinomas are rare biliary tract tumors that are often challenging to diagnose and treat. Cholangiocarcinomas are generally categorized as intrahepatic or extrahepatic depending on their anatomic location. The majority of patients with cholangiocarcinoma do not have any of the known or suspected risk factors and present with advanced disease. The optimal evaluation and management of patients with cholangiocarcinoma requires thoughtful integration of clinical information, imaging studies, cytology and/or histology, as well as prompt multidisciplinary evaluation. The current review focuses on recent advances in the diagnosis and treatment of patients with cholangiocarcinoma and, in particular, on the role of endoscopy, surgery, transplantation, radiotherapy, systemic therapy, and liver-directed therapies in the curative or palliative treatment of these individuals. Cancer 2016;122:1349-1369. © 2016 American Cancer Society.
188 citations
Cites background from "Outcomes of stereotactic body radio..."
...One series treated 58 patients with unresectable primary or recurrent cholangiocarcinoma with SBRT (53 patients) or SBRT boost after conventionally fractionated externalbeam RT (5 patients).(206) The median prescribed dose was 45 Gy in 3 fractions, and the median tumor volume was 40 mL (range, 5-1287 mL)....
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19 May 2016
TL;DR: 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.
Abstract: 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.
91 citations
TL;DR: Active local treatment (i.e., surgery, transarterial chemoembolization [TACE], and radiofrequency ablation [RFA]) may improve survival for patients with localized ICC recurrence.
Abstract: This study aimed to analyze the postoperative outcomes for patients with recurrent intrahepatic cholangiocarcinoma (ICC) and to determine the prognostic factors. In addition, this study investigated the effects of various treatment methods for patients with recurrent ICC. This retrospective study analyzed the postoperative outcomes and prognostic factors of recurrent ICC that occurred for 81 of 128 patients who underwent hepatic resection for ICC between April 2001 and April 2013. In addition, the outcomes for a number of treatment methods were assessed for patients with recurrent ICC. After resection, the 128 patients with ICC had survival rates of 73 % at 1 year, 52 % at 3 years, and 43 % at 5 years. Recurrent ICC developed in 81 patients (56 men and 25 women) with a median age of 63 years. The median time from initial resection to recurrence was 9 months (range, 0–124 months), and the median survival time after recurrence was 8 months (range, 0–108 months). After recurrence, the overall survival rates were 47 % at 1 year, 23 % at 3 years, and 15 % at 5 years. Multivariate analysis showed disease-free survival time shorter than 1 year and bile duct invasion to be significant prognostic factors. Among the treatment methods, local management such as surgery, transarterial chemoembolization, and radiofrequency ablation were effective in select cases with localized intrahepatic and extrahepatic recurrence. Active local treatment (i.e., surgery, transarterial chemoembolization [TACE], and radiofrequency ablation [RFA]) may improve survival for patients with localized ICC recurrence.
52 citations
TL;DR: SBRT is a promising option for patients with unresectable or recurrent cholangiocarcinoma either as a component of neoadjuvant therapy prior to OLT or as part of definitive therapy for patients who are unresectables and not eligible for transplantation.
Abstract: Objectives We report single-institution clinical efficacy and safety outcomes for patients with unresectable locally advanced cholangiocarcinoma who were treated with stereotactic body radiation therapy (SBRT) and a subset of patients who received neoadjuvant SBRT and chemotherapy as part of an orthotopic liver transplantation (OLT) protocol Methods and materials From October 2008 to June 2015, 31 consecutive patients with unresectable extrahepatic (n = 25) or intrahepatic (n = 6) cholangiocarcinoma were treated with SBRT and retrospectively analyzed Four patients underwent liver transplantation, and 1 underwent resection SBRT was delivered in 5 fractions with a median dose of 40 Gy Toxicity was scored using the Common Terminology Criteria for Adverse Events Version 40 Overall survival (OS), time to progression, and local control were estimated using the Kaplan-Meier method Results The median follow-up time was 115 months The 1- and 2-year OS rates were 59% and 33%, respectively, with a median survival of 157 months The 1- and 2-year freedom from progression was 67% and 34%, respectively Median time to progression was 168 months Nine patients had local failure The actuarial 1- and 2-year local control rates were 78% and 47%, respectively Among patients who also had OLT, the median OS was 313 months Twenty-four patients (77%) experienced some form of acute grade 1-2 toxicity, most commonly fatigue or pain Five patients (16%) experienced grade ≥3 toxicity Conclusions SBRT is a promising option for patients with unresectable or recurrent cholangiocarcinoma either as a component of neoadjuvant therapy prior to OLT or as part of definitive therapy for patients who are unresectable and not eligible for transplantation
44 citations
Cites background from "Outcomes of stereotactic body radio..."
...To our knowledge, this is the largest report on patients with primarily extrahepatic cholangiocarcinoma who were treated with SBRT....
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...Local progressive disease on imaging was defined using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 if applicable, or as increase in fluorodeoxyglucose (FDG) avidity on PET compared with fluorodeoxyglucose prior to SBRT....
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...The third study was a larger series that was published in 2014 and included 58 patients (half with primary tumors and half with recurrent disease) who were treated with SBRT.19 The rates of local control at 1- and 2-year follow-up were 85% and 72%, respectively....
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...The third study was a larger series that was published in 2014 and included 58 patients (half with primary tumors and half with recurrent disease) who were treated with SBRT.(19) The rates of local control at 1- and 2-year follow-up were 85% and 72%, respectively....
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TL;DR: ALBI score was similarly able to predict hepatic function decline compared with CP score, and both systems correlated with survival.
Abstract: Purpose This study aims to determine how the albumin-bilirubin (ALBI) score compares with the Child-Pugh (CP) score for assessing liver function following stereotactic body radiation therapy (SBRT). Methods and materials In total, 60 patients, 40 with hepatocellular carcinoma (HCC) and 20 with cholangiocarcinoma (CCA), were treated with SBRT. Liver function panels were obtained before and at 1, 3, 6, and 12 months after SBRT. Laboratory values were censored after locoregional recurrence, further liver-directed therapies, or liver transplant. Results A significant decline in hepatic function occurred after SBRT for HCC patients only ( P = .001 by ALBI score; P P = .0005; by CP, P P = NS; by CP, P = .008). Conclusions ALBI score was similarly able to predict hepatic function decline compared with CP score, and both systems correlated with survival.
39 citations
References
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TL;DR: Individualized six-fraction SBRT is a safe treatment for unresectable HCC and IHC and no radiation-induced liver disease or treatment-related grade 4/5 toxicity was seen within 3 months after S BRT.
Abstract: Purpose To report outcomes of a phase I study of individualized stereotactic body radiotherapy treatment (SBRT) for unresectable hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC). Patients and Methods Patients with unresectable HCC or IHC, and who are not suitable for standard therapies, were eligible for six-fraction SBRT during 2 weeks. Radiation dose was dependent on the volume of liver irradiated and the estimated risk of liver toxicity based on a normal tissue complication model. Toxicity risk was escalated from 5% to 10% and 20%, within three liver volume–irradiated strata, provided at least three patients were without toxicity at 3 months after SBRT. Results Forty-one patients with unresectable Child-Pugh A HCC (n = 31) or IHC (n = 10) completed six-fraction SBRT. Five patients (12%) had grade 3 liver enzymes at baseline. The median tumor size was 173 mL (9 to 1,913 mL). The median dose was 36.0 Gy (24.0 to 54.0 Gy). No radiation-induced liver disease or treatment-related gra...
515 citations
"Outcomes of stereotactic body radio..." refers background in this paper
...Several studies have shown SBRT results with few patients enrolled [3,11-13]....
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TL;DR: The results suggest that, compared with historical controls, high-dose focal liver irradiation with hepatic artery floxuridine prolongs survival in patients with unresectable chemotherapy-refractory metastatic colorectal cancer and primary hepatobiliary tumors.
Abstract: Purpose A phase II trial was conducted to determine if high-dose radiation with concurrent hepatic arterial floxuridine would improve survival in patients with unresectable intrahepatic malignancies. Patients and Methods Three-dimensional conformal high-dose radiation therapy was delivered concurrently with hepatic arterial floxuridine in 128 patients. The radiation dose was based on a normal-tissue complication probability model and subjected the patient to an estimated maximum risk of radiation-induced liver disease of 10% to 15%. The study design provided more than 80% power to detect a two-fold increase in median survival compared with historical controls at a 5% significance level. Results The median radiation dose delivered was 60.75 Gy (1.5-Gy fractions bid). At a median follow-up time of 16 months (26 months in patients who were alive) the median survival was 15.8 months (95% CI, 12.6 to 18.3 months), significantly longer than in the historical control. The actuarial 3-year survival was 17%. The t...
302 citations
TL;DR: Patients with localized CCA who are selected for CDS are strongly associated with improved survival, with rates approaching that found in single institution studies, however, many patients with localized tumors do not receive potentially curative cancer-directed surgery.
Abstract: Background
Cholangiocarcinoma (CCA) is associated with poor survival and therapeutic nihilism. To date, there has not been an examination of the surgical management of CCA at a population level.
176 citations
"Outcomes of stereotactic body radio..." refers background in this paper
...Resectability rates are generally low, usually less than 30% [1]....
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TL;DR: A dose response is shown with more than double the 2-year and median survival for doses > 55 Gy, and high dose combined brachytherapy and external beam radiation (60-75 Gy) appears to be the most effective modality for extrahepatic bile duct cancer.
Abstract: Purpose: To examine the impact of radiation dose on both survival and morbidity in combined modality treatment of bile duct cancer. Methods and Materials: Forty-eight patients with cancer of the extrahepatic bile ducts were treated at Thomas Jefferson University Hospital from 1984–1990. Twenty-four patients received radiation as part of a combined modality approach using external beam radiation, brachytherapy implant and chemotherapy. Twenty-four patients received no radiation in the course of their treatment. Radiation was delivered via high energy photons at standard fractionation, 5 days/week, for an average of 46 Gy. The implant used Ir-192 ribbon sources (average activity was 29 mCi, active length was 6 cm) for a mean dose of 25 Gy at 1 cm. Chemotherapy consisted of 5-FU alone or combined with adriamycin or mitomycin-C. Results: Two-year survival for all 48 patients was 18% (median 9 months). Patients treated with radiation had a 2-year survival of 30% (median 12 months) vs. the no-radiation group, 17% (5.5 months, median), p = 0.01. Those treated to > 55 Gy experienced an extended 2-year survival of 48% (24 months, median), vs. those receiving p = 0.0003. This benefit was also seen when patients were stratified by T-stage. A dose response is further suggested by a lengthening of the median survival with increasing radiation dose (4.5 months, 9 months, 18 months and 25 months for Conclusion: A dose response is shown with more than double the 2-year and median survival for doses > 55 Gy. A brachytherapy dose of 25 Gy, plus 44–46 Gy external beam is well tolerated. High dose combined brachytherapy and external beam radiation (60–75 Gy) appears to be the most effective modality for extrahepatic bile duct cancer.
162 citations
"Outcomes of stereotactic body radio..." refers background in this paper
...5, 9, 18, and 25 months for <45, 45–55, 55– 65, and 66–70 Gy, respectively) [5]....
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...Early results using EBRT and brachytherapy have demonstrated a doseresponse relationship [4-6]....
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...A study by Alden and Mohiuddin [5] treated 48 patients with extrahepatic bile duct cancers....
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TL;DR: The outcomes of SBRT for unresectable cholangiocarcinoma appear comparable to conventionally fractionated chemoradiotherapy with or without brachytherapy boost, and patient selection is key to avoid compromising such practical gains with excessive gastrointestinal toxicity.
142 citations
"Outcomes of stereotactic body radio..." refers background in this paper
...The largest series until now include 27 patients with unresectable cholangiocarcinoma treated with SBRT [12]....
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...Several studies have shown SBRT results with few patients enrolled [3,11-13]....
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