Unresectable Perihilar Cholangiocarcinoma Research Articles

Efficacy and safety of irreversible electroporation in unresectable perihilar cholangiocarcinoma: a systematic review and meta-analysis.

The prognosis of patients with perihilar-cholangiocarcinoma (PHC) is poor. The only potential curative treatment for patients with PHC is surgical resection, but the large majority present with unresectable disease at diagnosis. The standard of care in patients with unresectable PHC is palliative chemotherapy (CHT).Irreversible electroporation (IRE) has been introduced as a novel ablation technique, working predominantly nonthermal. This review aims to analyse the efficacy and safety of IRE in treating unresectable PHC. This systematic review and meta-analysis was performed according to a specific protocol designed a priori, and reported according to the PRISMA. PubMed/MEDLINE, Scopus, and Cochrane CENTRAL were used for the bibliographic research through December 2023. Primary Outcome of interest of our meta-analysis was the mean Overall Survival. Secondary outcomes were Progression-Free Survival and Adverse Event rate. Mean OS is estimated to be 25.49 months (CI 21.47-38.72 I2, 81.37%), PSF 17.86 (CI 13.00-22.72, I2 11.42%), with 12% (CI -7% to 31%, I2 83.57%) of AE incidence. High heterogeneity was found among studies, with no single study fully responsible for it, suggesting high variability among facilities\populations. IRE is an effective and relatively safe method in this group of patients. The lack of prospective studies and randomized trials comparing chemotherapy or locoregional treatment with IRE prevents drawing sufficiently robust conclusions. IRE appears is a safe and effective technique for treating unresectable perihilar cholangiocarcinoma.

Cholangio-jejunostomy on segment 3 duct for palliative treatment of unresectable perihilar cholangiocarcinoma

Cholangio-jejunostomy on segment 3 duct for palliative treatment of unresectable perihilar cholangiocarcinoma

The Short- and Long-Term Surgical Results of Consecutive Hepatopancreaticoduodenectomy for Wide-Spread Biliary Malignancy.

Cancer-free resection (R0) is one of the most important factors for the long-term survival of biliary carcinoma. For some patients with widespread invasive cancer located between the hilar and intrapancreatic bile duct, hepatopancreaticoduodenectomy (HPD) is considered a radical surgery for R0 resection. However, HPD is associated with high morbidity and mortality rates. Furthermore, previous reports have not shown lymph node metastasis (LNM) status, such as the location or number, which could influence the prognosis after HPD. In this study, first, we explored the prognostic factors for survival, and second, we evaluated whether the LNM status (number and location of LNM) would influence the decision on surgical indications in patients with widely spread biliary malignancy. We retrospectively reviewed the medical records of 54 patients who underwent HPD with hepatectomy in ≥2 liver sectors from January 2003 to December 2021 (HPD-G). We also evaluated 54 unresectable perihilar cholangiocarcinoma patients who underwent chemotherapy from January 2010 to December 2021 (CTx-G). R0 resection was performed in 48 patients (89%). The median survival time (MST) and 5-year overall survival rate of the HPD-G and CTx-G groups were 36.9 months and 31.1%, and 19.6 months and 0%, respectively. Univariate and multivariate analyses showed that pathological portal vein involvement was an independent prognostic factor for survival (MST: 18.9 months). Additionally, patients with peripancreatic LNM had worse prognoses (MST: 13.3 months) than CTx-G. Patients with peripancreatic LNM or PV invasion might be advised to be excluded from surgery-first indications for HPD.

Impact of EUS in liver transplantation workup for patients with unresectable perihilar cholangiocarcinoma

Background and study aimsFor a highly selected group of patients with unresectable perihilar cholangiocarcinoma (pCCA) liver transplantation (LT) is a treatment option. The Dutch screening protocol comprises non-regional lymph node (LN) assessment by endoscopic ultrasound (EUS) and whenever LN metastases are identified, further LT screening is precluded. The aim of this study is to investigate the yield of EUS in patients with pCCA who are potentially eligible for LT. MethodsIn this retrospective, nationwide cohort study, all consecutive patients with suspected unresectable pCCA who underwent EUS in the screening protocol for LT were included from 2011-2021. During EUS, sampling of a ‘suspicious’ non-regional LN was performed based on the endoscopists discretion. The primary outcome was the added value of EUS, defined as number of patients who were precluded from further screening due to malignant LN. ResultsA total of 75 patients was included in whom 84 EUS procedures were performed, with EUS guided tissue acquisition confirming malignancy in LN in 3/75 (4%) patients. In the 43 who underwent surgical staging conform the protocol, non-regional LN were identified in 6 (14%) patients. Regional LN were found in 7 patients in post-LT resected specimens. ConclusionsOur current EUS screening for the detection of malignant LN in patients with pCCA eligible for LT shows a limited but clinically important yield. EUS with systematic screening of all LN stations, both regional and non-regional and sampling of ‘suspicious’ lymph nodes according to defined and set criteria could potentially increase this yield.

National consensus on a new resectability classification for perihilar cholangiocarcinoma - A modified Delphi method

BackgroundCurrently, no practical definition of potentially resectable, borderline or unresectable perihilar cholangiocarcinoma (pCCA) is available. Aim of this study was to define criteria to categorize patients for use in a future neoadjuvant or induction therapy study. MethodUsing the modified DELPHI method, hepatobiliary surgeons from all tertiary referral centers in the Netherlands were invited to participate in this study. During five online meetings, predefined factors determining resectability and additional factors regarding surgical resectability and operability were discussed. ResultsThe five online meetings resulted in 52 statements. After two surveys, consensus was reached in 63% of the questions. The main consensus included a definition regarding potential resectability. 1) Clearly resectable: no vascular involvement (≤90°) of the future liver remnant (FLR) and expected feasibility of radical biliary resection. 2) Clearly unresectable: non-reconstructable venous and/or arterial involvement of the FLR or no feasible radical biliary resection. 3) Borderline resectable: all patients between clearly resectable and clearly unresectable disease. ConclusionThis DELPHI study resulted in a practical and applicable resectability, or more accurate, an explorability classification, which can be used to categorize patients for use in future neoadjuvant therapy studies.

Essential updates 2021/2022: Update in surgical strategy for perihilar cholangiocarcinoma.

Resection is the only potential curative treatment for perihilar cholangiocarcinoma (PHC); however, complete resection is often technically challenging due to the anatomical location. Various innovative approaches and procedures were invented to circumvent this limitation but the rates of postoperative morbidity (20%-78%) and mortality (2%-15%) are still high. In patients diagnosed with resectable PHC, deliberate and coordinated preoperative workup and optimization of the patient and future liver remnant are crucial. Biliary drainage is recommended to relieve obstructive jaundice and optimize the clinical condition before liver resection. Biliary drainage for PHC can be performed either by endoscopic biliary drainage or percutaneous transhepatic biliary drainage. To date there is no consensus about which method is preferred. The volumetric assessment of the future remnant liver volume and optimization mainly using portal vein embolization is the gold standard in the management of the risk to develop post hepatectomy liver failure. The improvement of systemic chemotherapy has contributed to prolong the survival not only in patients with unresectable PHC but also in patients undergoing curative surgery. In this article, we review the literature and discuss the current surgical treatment of PHC.

Segment 3 cholangiojejunostomy for unresectable peri‐hilar cholangiocarcinoma: A case report and literature review

AbstractSurgical management of unresectable perihilar cholangiocarcinoma is no longer relevant. Often these patients benefit from less invasive endoscopic or radiological management, but in the event of failure of these techniques, and in selected patients, cholangiojejunostomy in segment 3 can be an effective option. We describe the case of a 48‐year‐old patient presenting with an unresectable perihilar cholangiocarcinoma, in whom palliative endoscopic management failed two times and an open segment 3 intrahepatic cholangiojejunostomy was performed. The patient was discharged on the 7th day, has a complete resolution of jaundice at 2 months and is alive at 6 months without any readmission.

Role of neoadjuvant chemoradiotherapy in liver transplantation for unresectable perihilar cholangiocarcinoma: multicentre, retrospective cohort study

The Mayo protocol for liver transplantation in patients with unresectable perihilar cholangiocarcinoma is based on strict selection and neoadjuvant chemoradiotherapy. The role of neoadjuvant chemoradiotherapy in this scenario remains unclear. The aim of this study was to compare outcomes after transplantation for perihilar cholangiocarcinoma using strict selection criteria, either with or without neoadjuvant chemoradiotherapy. This was an international, multicentre, retrospective cohort study of patients who underwent transplantation between 2011 and 2020 for unresectable perihilar cholangiocarcinoma using the Mayo selection criteria and receiving neoadjuvant chemoradiotherapy or not receiving neoadjuvant chemoradiotherapy. Endpoints were post-transplant survival, post-transplant morbidity rate, and time to recurrence. Of 49 patients who underwent liver transplantation for perihilar cholangiocarcinoma, 27 received neoadjuvant chemoradiotherapy and 22 did not. Overall 1-, 3-, and 5-year post-transplantation survival rates were 65 per cent, 51 per cent and 41 per cent respectively in the group receiving neoadjuvant chemoradiotherapy and 91 per cent, 68 per cent and 53 per cent respectively in the group not receiving neoadjuvant chemoradiotherapy (1-year hazards ratio (HR) 4.55 (95 per cent c.i. 0.98 to 21.13), P = 0.053; 3-year HR 2.07 (95 per cent c.i. 0.78 to 5.54), P = 0.146; 5-year HR 1.71 (95 per cent c.i. 0.71 to 4.09), P = 0.229). Hepatic vascular complications were more frequent in the group receiving neoadjuvant chemoradiotherapy compared with the group not receiving neoadjuvant chemoradiotherapy (nine of 27 versus two of 22, P = 0.045). In multivariable analysis, tumour recurrence occurred less frequently in the group receiving neoadjuvant chemoradiotherapy (HR 0.30 (95 per cent c.i. 0.09 to 0.97), P = 0.044). In selected patients undergoing liver transplantation for perihilar cholangiocarcinoma, neoadjuvant chemoradiotherapy resulted in a lower risk of tumour recurrence, but was associated with a higher rate of early hepatic vascular complications. Adjustments in neoadjuvant chemoradiotherapy reducing the risk of hepatic vascular complications, such as omitting radiotherapy, may further improve the outcome in patients undergoing liver transplantation for perihilar cholangiocarcinoma.

Feasibility and Efficacy of Adjuvant Chemotherapy With Gemcitabine After Liver Transplantation for Perihilar Cholangiocarcinoma - A Multi-Center, Randomized, Controlled Trial (pro-duct001)

Liver transplantation (LT) is considered a therapeutic option for unresectable perihilar cholangiocarcinoma (PHC) within defined criteria. It remains uncertain whether patients can safely receive adjuvant chemotherapy after LT. We performed a prospective, multi-center, randomized, non-blinded two-arm trial (pro-duct001). Patients after LT for unresectable PHC within defined criteria were randomized to adjuvant gemcitabine (LT-Gem group) and LT alone (LT alone group). The primary objective was to investigate if adjuvant chemotherapy is feasible in ≥ 85% of patients after LT. The primary endpoint was the percentage of patients completing the 24 weeks course of adjuvant chemotherapy. Secondary endpoints included overall survival (OS) and disease-free (DFS), and complication rates. Twelve patients underwent LT for PHC, of which six (50%) were eligible for randomization (LT-Gem: three patients, LT alone: three patients). Two out of three patients discontinued adjuvant chemotherapy after LT due to intolerance. The study was prematurely terminated due to slow enrollment. One patient with PHC had underlying primary sclerosing cholangitis (PSC). Tumor-free margins could be achieved in all patients. In both the LT-Gem and the LT alone group, the cumulative 1-, 3-, and 5-year OS and DFS rates were 100%, 100%, 67%, and 100%, 67% and 67%, respectively. This prospective, multi-center study was prematurely terminated due to slow enrollment and a statement on the defined endpoints cannot be made. Nevertheless, long-term survival data are consistent with available retrospective data and confirm defined criteria for LT. Since more evidence of LT per se in unresectable PHC is urgently needed, a prospective, non-randomized follow-up study (pro-duct002) has since been launched.

Surgery of extrahepatic bile duct cancer - current evidence and recommendations.

Extrahepatic cholangiocarcinoma is a rare disease with poor prognosis, requiring comprehensive multidisciplinary management. Only radical resection gives hope for long-term survival. Most patients have either an unresectable disease or their condition does not allow for radical surgery. The method of choice for resectable perihilar cholangiocarcinoma is en-block liver resection including the extrahepatic bile duct, or pancreatoduodenectomy for distal cholangiocarcinoma. Hepatopancreatoduodenectomy can be performed in selected patients if the entire hepato-choledochus is affected. Liver transplantation after neoadjuvant treatment can be also considered in highly selected patients with unresectable perihilar cholangiocarcinoma. These procedures are technically demanding, are associated with high morbidity and relevant mortality, and must be concentrated in tertiary hepatobiliary centers. Preoperative optimization (bile duct drainage, nutrition, portal venous embolization, etc.) plays a crucial role in reducing postoperative morbidity and mortality.

Success, complication, and mortality rates of initial biliary drainage in patients with unresectable perihilar cholangiocarcinoma

BackgroundThe patients with unresectable perihilar cholangiocarcinoma require biliary drainage to relieve symptoms and allow for palliative systemic chemotherapy. The aim of this study was to establish the success, complication, and mortality rates of the initial biliary drainage in patients with unresectable perihilar cholangiocarcinoma at presentation. MethodsIn this retrospective multicenter study, patients with unresectable perihilar cholangiocarcinoma who underwent initial endoscopic or percutaneous transhepatic biliary drainage between 2002 and 2014 were included. The success of drainage was defined as a successful biliary stent or drain placement, no unscheduled reintervention within 14 days, and serum bilirubin levels <50 μmol/L (ie, 2.9 mg/dL) or a >50% decrease in serum bilirubin after 14 days. Severe complications, and 90-day mortality were recorded. ResultsIncluded were 186 patients: 161 (87%) underwent initial endoscopic biliary drainage and 25 (13%) underwent initial percutaneous transhepatic biliary drainage. The success of initial drainage was observed in 73 patients (45%) after endoscopic biliary drainage and 6 (24%) after percutaneous transhepatic biliary drainage. The reasons for an unsuccessful initial drainage were: the failure to place a drain or stent in 39 patients (21%), an unplanned reintervention within 14 days in 52 patients (28%), and the bilirubin level >50 μmol/L (or not halved) after 14 days of initial drainage in 16 patients (9%). Severe drainage-related complications occurred in 19 patients (12%) after endoscopic biliary drainage and in 3 (12%) after percutaneous transhepatic biliary drainage. Overall, 66 patients (36%) died within 90 days after initial biliary drainage. ConclusionInitial biliary drainage in patients with unresectable perihilar cholangiocarcinoma had a success rate of 45% and a 90-day mortality rate of 36%. Future studies for patients with perihilar cholangiocarcinoma should focus on improving biliary drainage.

Comparison of Intraductal RFA Plus Stent versus Stent-Only Treatment for Unresectable Perihilar Cholangiocarcinoma-A Systematic Review and Meta-Analysis.

Simple SummaryIn patients with unresectable perihilar cholangiocarcinoma, adequate biliary drainage is essential. Stent patency remains a challenge in these complex patients, as both plastic and metal stent occlusion may occur, necessitating additional drainage procedures. Radiofrequency ablation (RFA) is a promising local treatment that has already proven its usefulness in other malignancies, such as hepatocellular carcinoma. In this meta-analysis and systematic review, we aimed to compare intraductal RFA with stent placement to stent placement alone in patients with unresectable perihilar cholangiocarcinoma. We found that RFA + stent treatment showed a significantly longer overall survival, in comparison to stent-only treatment. Further research is necessary in order to validate these findings to support the implementation of this promising strategy in clinical practice.Background: One of the cornerstones of palliative treatment for unresectable perihilar cholangiocarcinoma is biliary stent placement in order to restore biliary drainage. In this review, the potential added value of RFA with stent placement in comparison to stent placement alone in patients with unresectable perihilar cholangiocarcinoma is analyzed. Methods: We performed a comprehensive online search for relevant articles in November 2021 (PROSPERO ID: CRD42021288180). The primary endpoint was difference in overall survival. Secondary endpoints included overall survival, stent patency and complications. Only studies comparing survival after RFA + stent placement with stent placement alone were included in the meta-analysis. Non-comparative studies or comparative studies describing stent patency only were included in the systematic review. Results: A total of nine studies, including 217 patients with pCCA who underwent RFA + stent placement and 294 patients who underwent stent-only treatment, met the inclusion criteria for the primary endpoint analysis. Direct comparison between the two treatment groups showed a significantly longer overall survival for RFA + stent treatment, with a pooled HR of 0.65 [95% CI, 0.50–0.84, I2 = 38%]. When all eligible studies were included, RFA + stent treatment revealed an overall survival of 9.5 months [95% CI, 6.3–12.6], whereas survival for stent-only treatment was 7.0 months [95% CI, 5.7–8.2]. Due to the heterogeneity of the data, no pooled data analysis could be performed on stent patency or complications. Conclusions: RFA + stent placement displays promising potential to prolong survival. However, further research incorporating confounding factors like use of palliative chemotherapy is necessary in order to validate these findings.

Outcomes of Irreversible Electroporation for Perihilar Cholangiocarcinoma: A Prospective Pilot Study

PurposeTo investigate the safety and efficacy of percutaneous or open irreversible electroporation (IRE) in a prospective cohort of patients with locally advanced, unresectable perihilar cholangiocarcinoma (PHC). Materials and MethodsIn a multicenter Phase I/II study, patients with unresectable PHC due to extensive vascular involvement or N2 lymph node metastases or local recurrence after resection for PHC were included and treated by open or percutaneous IRE combined with palliative chemotherapy (current standard of care). The primary outcome was the number of major adverse events occurring within 90 d after IRE (grade ≥3), and the upper limit was predefined at 60%. Secondary outcomes included technical success rate, hospital stay, and overall survival (OS). ResultsTwelve patients (mean age, 63 y ± 12) were treated with IRE. The major adverse event rate was 50% (6 of 12 patients), and no 90-d mortality was observed. All procedures were technically successful, with no intraprocedural adverse events requiring additional interventions. The median OS from diagnosis was 21 mos (95% confidence interval, 15–27 mos), with a 1-y survival rate of 75% after IRE. ConclusionsPercutaneous IRE in selected patients with locally advanced PHC seems feasible, with a major adverse event rate of 50%, which was below the predefined upper safety limit in this prospective study. Future comparative research exploring the efficacy of IRE is warranted.

Performance of Initial Biliary Drainage in Patients with Unresectable Perihilar Cholangiocarcinoma

Introduction: Patients with unresectable perihilar cholangiocarcinoma (pCCA) require biliary drainage to relieve symptoms and allow for palliative systemic chemotherapy. The aim of this study was to establish the success, complication, and mortality rates of the initial biliary drainage procedure in patients with unresectable pCCA.

Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma: Is Neo-Adjuvant Chemo-Radiation Therapy Really Necessary? An International, Multicenter Comparison

Introduction: The Mayo Clinic protocol for patients with unresectable perihilar cholangiocarcinoma (pCCA) is based on strict selection and neo-adjuvant chemo-radiation therapy (NAT) followed by liver transplantation (LT). With this protocol, 5-year survival up to 68% has been reported. It remains unclear whether these favorable results are attributable to NAT or strict selection only. Our aim was to compare outcomes after LT for unresectable pCCA after strict selection between patients with or without NAT. Method: International, multicenter, comparison of two cohorts of patients transplanted between 2011-2021, for unresectable pCCA using the Mayo Clinic selection criteria and receiving NAT (NAT+) or not (NAT-). Primary endpoint was overall survival. Secondary outcomes included post-transplant morbidity (including vascular complications) and tumor recurrence evaluated by inverse-probability-weighting and competing risk analysis. Results: A total of 49 patients underwent LT for unresectable pCCA (NAT+ n=27, NAT- n=22). Median age was 55 years. Median follow-up was 25 months. In the NAT+ group, the 1-, 3- and 5-year survival rates were 65%, 51% and 41%, respectively, compared to 91%, 68% and 53% for NAT- patients (p=0.20; Figure). Tumor 5-year recurrence rate was similar between groups: 32% in the NAT+ group versus 53% in the NAT- group (p=0.55). Major vascular complications (Clavien-Dindo grade ≥3A) post-LT were significantly higher in the NAT+ cohort with 11 patients (41%) versus 3 patients (14%) (p=0.04). Conclusions: Survival after LT for pCCA in strictly selected patients did not differ between patients with or without NAT. Post-transplant vascular complications were significantly higher in patients after NAT.

Endobiliary Ablation Improves Survival in Patients With Unresectable Perihilar Cholangiocarcinoma Compared to Stenting Alone

Background and AimsPalliative ERCP-directed photodynamic therapy (PDT) and radiofrequency ablation (RFA) are available to treat biliary obstruction from perihilar cholangiocarcinoma (pCCA), but data comparing endobiliary ablation with stenting to biliary stenting alone in these patients are lacking. The aims of this study were to compare (1) survival and (2) frequencies of adverse events in patients with unresectable pCCA who underwent endobiliary ablation and stenting vs biliary stenting alone. MethodsRetrospective cohort study that included 59 patients with unresectable pCCA treated with ERCP-directed biliary ablation (RFA and/or PDT) and stenting (n = 30) or biliary stenting alone (n = 29). The main outcome of interest was survival in patients who underwent any form of endobiliary ablation (RFA and/or PDT) and stenting vs biliary stenting alone, as determined by multivariate Cox proportional hazards modeling analysis. ResultsPatients who underwent any form of endobiliary ablation and stenting had improved survival (10.0 months, 95% CI: 8.4-27.5) compared to biliary stenting alone (6.1 months, 95% CI: 4.8-8.8; adjusted hazard ratio 3.2, 95% CI: 1.3-7.6, P = 0.010), without any difference in the frequencies of adverse events. RFA and stenting was shown to improve survival (10.0 months, 95% CI: 8.5-36.8) compared to stenting alone (6.7 months, 95% CI: 5.4-8.8; adjusted hazard ratio 3.5, 95% CI: 1.3-9.3, P = 0.012). ConclusionEndobiliary ablation (with RFA and/or PDT or RFA alone) followed by stenting was associated with significantly improved survival compared to biliary stenting alone in patients with unresectable pCCA, without an increase in adverse events, and should be offered as first-line palliative therapy.

Stereotactic Body Radiation Therapy Following Chemotherapy for Unresectable Perihilar Cholangiocarcinoma: The STRONG Trial, a Phase I Feasibility Study

<h3>Purpose/Objective(s)</h3> Patients with perihilar cholangiocarcinoma (pCCA) can only be cured by surgery. The standard of care for those with inoperable tumors is palliative chemotherapy. In an attempt to control the disease locally without adding severe toxicity in patients with unresectable pCCA, we investigated the safety and feasibility of adding stereotactic body radiation therapy (SBRT) after chemotherapy. <h3>Materials/Methods</h3> Patients were eligible with a diagnosis of unresectable pCCA, stage T1-T4N0-N1M0 (AJCC staging 7th edition), ECOG performance status of 0-1, and having finished 6-8 cycles chemotherapy treatment (cisplatin and gemcitabine). SBRT was planned in 15 fractions of 3.0-4.5Gy, aiming for a biologically effective dose > 80.5Gy, while not exceeding organs at risk (OAR) constraints. The primary endpoints were feasibility, defined as completing SBRT as planned, and toxicity evaluated within 3 months of treatment. A conventional ‘3+3'-design was used, corresponding to a sample size of 6 patients. Toxicity was scored with the CTCAE v4.03 grading system. Dose-limiting toxicity (DLT) was defined as grade ≥4 hepatobiliary or grade ≥3 gastrointestinal toxicity. Secondary endpoints, measured from start of radiotherapy, were local control, progression-free survival (RECIST 1.1), overall survival, and quality of life (QoL). QoL was measured using the QLQ-C30, EQ-5D-5L, and QLQ-BIL21 questionnaires. <h3>Results</h3> Six patients were enrolled between 1 November 2017 and 30 March 2020. All patients completed 6-8 cycles of chemotherapy. They were staged T4N0-1M0, each with unresectable disease due to vascular involvement. SBRT was completed as planned. A dose of 60Gy (15×4.0Gy) was prescribed at the 80% isodose. Due to OAR constraints, especially duodenum, the median PTV coverage was limited to 82.4% (75.7%-89.6%). No SBRT related DLT was observed. The most common grade ≥3 toxicity was cholangitis (n = 5), which could be resolved by improving biliary drainage. The 12-month local control rate was 80%. Metastases emerged in the form of peritoneal metastases/ascites (n = 3) and/or liver metastases (n = 1). Three of the 4 patients who developed distant metastases had lymph-node-positive disease at baseline. After a median follow up of 14 months, 4 of 6 patients were still alive. We observed no substantial changes in QoL. Median QLQ-C30 ‘global health status' scores were 75.0 at baseline, 3 months and 12 months. <h3>Conclusion</h3> Fractionated SBRT following standard chemotherapy was a feasible and safe local therapy option for unresectable pCCA, albeit with the use of hard constraints for OAR. Cholangitis was often observed, but was reversible and QoL was maintained. Based upon the observed safety and the promising local control, additional evaluation of effectiveness in larger studies is warranted.

Response to the Comment on “Meta-analysis and Meta-regression of Survival After Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma”

Response to the Comment on “Meta-analysis and Meta-regression of Survival After Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma”

Stereotactic Body Radiation Therapy after Chemotherapy for Unresectable Perihilar Cholangiocarcinoma: The STRONG Trial, a Phase I Safety and Feasibility Study.

Simple SummaryThe role of radiotherapy in the treatment of perihilar cholangiocarcinoma has not yet been properly defined. In this prospective study, we therefore explored the addition to first-line chemotherapy of stereotactic body radiation therapy (SBRT) delivered in 15 fractions. Patients eligible for the study had been diagnosed with unresectable perihilar cholangiocarcinoma, and then had no progressive disease after completing treatment with 6–8 cycles of cisplatin-gemcitabine. Primary endpoints were feasibility and safety. Secondary endpoints were local control, progression-free survival, overall survival, and quality of life. As each patient completed the SBRT successfully and no dose-limiting toxicity was found, we consider this treatment to be both feasible and safe. The local control rate and overall survival were promising. However, due to the small sample size of this study, we urge the analysis of this treatment in a larger series of patients.Background: In unresectable pCCA, the standard of care is palliative chemotherapy. We investigated the feasibility and safety of adding stereotactic body radiation therapy (SBRT) after chemotherapy. Methods: Patients with unresectable pCCA, stage T1-T4N0-N1M0, ECOG 0-1, having finished 6–8 cycles of cisplatin and gemcitabine without disease progression were eligible. SBRT was planned in 15 fractions of 3.0–4.5 Gy. The primary endpoints were feasibility (defined as completing SBRT as planned) and toxicity, evaluated within 3 months after SBRT (CTCAE v4.03). A conventional “3 + 3” design was used, corresponding to a sample size of 6 patients. Dose-limiting toxicity (DLT) was defined as grade ≥ 4 hepatobiliary or grade ≥ 3 gastrointestinal toxicity. The secondary endpoints, measured from the start of radiotherapy, were local control, progression-free survival, overall survival, and quality of life (QoL). ClinicalTrials.gov identifier: NCT03307538. Results: Six patients were enrolled between November 2017 and March 2020. SBRT was delivered as planned. All patients were treated with 60Gy (15 × 4.0Gy). No SBRT-related DLT was observed. The most common grade ≥ 3 toxicity was cholangitis (n = 5). The median follow-up was 14 months. The 12-month local control rate was 80%. We observed no substantial changes in QoL. Conclusion: In patients with unresectable pCCA with stable disease after palliative chemotherapy, adding SBRT is feasible and safe. The observed local control merits an additional evaluation of effectiveness.

Endoscopic techniques and common pitfalls for nasobiliary catheter placement to facilitate delivery of high-dose intraductal brachytherapy in cholangiocarcinoma

Liver transplantation has been increasingly offered as a curative treatment option to a highly selected group of patients with unresectable perihilar cholangiocarcinoma.1 Patients who meet the transplant criteria at our institution undergo a protocolized therapy with neoadjuvant chemoradiation and brachytherapy followed by liver transplantation, with a 5-year disease-free survival rate of 55% to 65%.2