Inoperable Cholangiocarcinoma Research Articles

Addition of stereotactic body radiotherapy (SBRT) to systemic chemotherapy in locally advanced cholangiocarcinoma (CC) (ABC-07): Results from a randomized phase II trial.

4006 Background: Locoregional treatments for inoperable, non-metastatic CC remain undefined. Single arm phase 2 data suggested that SBRT may improve clinical outcomes. We aimed to investigate the efficacy and safety of the addition SBRT with CisGem in locally advanced inoperable CC. Methods: ABC-07 (ISRCTN:10639376) is a phase II multicentre randomized trial for patients with inoperable, histologically confirmed locally advanced CC, WHO performance status 0-1. After registration patients showing no progression after 4 cycles of CisGem were randomized (2:1) for treatment after completing six cycles: either SBRT (50 Gy in 5 fractions or 67.5 Gy in 15 fractions, based on tumour size) or two additional cycles (cycles 7 and 8) of CisGem (CG-only). Primary endpoint was progression free survival (PFS). With 80% power and a 15% one-sided alpha, the study planned to randomize 65 patients to detect a median PFS increase from 10.4 to 17.4 months. Secondary endpoints included overall survival (OS), toxicity and patterns of failure. RT quality assurance was undertaken. Results: Between March 2016 and August 2022, 16 UK centres randomized 69 patients (SBRT, 45; CG only, 24). Median age was 66 (38 to 83) yrs, 58 (84.1%) perihilar location, 48(69.6%) stent in situ, median tumor size was 3.5cm (range 0.6-10.5). The median follow-up time was 20.7 months. In the SBRT arm, 43 completed 6 cycles CisGem (96%) and 41 (91%) received SBRT. In the CG-only arm, 18 (75%) completed 8 cycles. The median PFS from randomization was 8.6 and 9.0 months in the SBRT and CG-only arms, respectively (HR: 1.00; 95% CI: 0.58,1.70; p = 0.989). The first PFS events were 7 (16%) local and 24 (53%) metastatic relapses for SBRT, versus 7 (29%) and 7 (29%) in the CG-only arm, respectively. From registration, median OS time was 23.4 (95% CI: 14.6, 27.7) months for SBRT and 17.2 (95% CI: 10.2, NR) months for CG-only arm. Post-randomization, OS was 19.4 months (11.2, 24.6) for SBRT and 14.2 (7.0, NR) months for CG-only (HR: 0.79; 95% CI: 0.41,1.51; p = 0.47). Adverse events of grade ≥3 were observed in 33 (73%) and 21 (88%) patients in SBRT and CG-only arms, respectively. Of the infections, of which biliary sepsis was common, pre-cycle 6, SBRT had 19 (42%) cases vs. 7 (29%) in CG-only; post-cycle 6, SBRT had 17 (38%) sepsis cases vs. 6 (25%) in CG-only. There was 1 Grade 3 duodenal hemorrhage and 1 death due to sepsis in the SBRT arm. Primary causes of death included disease (20, 44% vs 11, 46%), sepsis (5, 11% vs 3, 13%), and hepatic failure (0 vs 3, 13%) for the SBRT and CG-only arms, respectively. Conclusions: SBRT did not show a PFS advantage over CG-only, yet a longer median OS time and better primary tumour control were observed without safety concerns. However, more mature survival data is still needed. Clinical trial information: 10639376.

Primary extranodal lymphoma: a report of six cases in a private cancer centre in Nigeria

Primary extra-nodal lymphoma (PENL) refers to lymphomas which present with disease in any organ or tissue other than lymph nodes or spleen. Symptoms at initial presentation are mainly from extra nodal involvement and after routine staging procedures, the extra nodal involvement remains the clinically dominant site of disease with little or no nodal disease [1, 2]. About 25–40% of lymphomas arise at extra nodal sites and with clinical presentation similar to solid tumors [3, 4] creating ambiguity in diagnosis and delays in treatment especially in resource poor settings. We report six cases of PENL seen at a private cancer centre in Lagos, Nigeria between 2021 and 2022. The age range was 32–95 years with five females and one male. Two patients were HIV positive. Five patients had initial symptoms of vague abdominal pain with one patient investigated multiple times for peptic ulcer disease. One patient presented with pathological fracture of left femur. Another patient had previously been diagnosed with an inoperable cholangiocarcinoma. All patients had non-Hodgkin’s lymphoma, DLBCL being most common (83.37%). Four patients started chemotherapy. All treated patients showed good outcomes with complete or good partial response highlighting the importance of accurate diagnosis. Initial histological diagnosis in most of the cases did not suggest lymphoma until immunohistochemistry (IHC) results were received. Cancer care in Nigeria is fraught with difficulties obtaining accurate diagnosis due in part to the limited availability of IHC and molecular testing facilities required to characterize the malignant cells leading to delays in treatment and poorer prognosis [6–8].

Image-Guided Ablation of Recurrent or Unresectable Intrahepatic Cholangiocarcinoma

PurposeTo assess the safety and effectiveness of image-guided ablation of recurrent or unresectable intrahepatic cholangiocarcinoma (ICC). Materials and MethodsIn this retrospective study, 25 patients (14 women; age, 36–84 years) underwent 37 image-guided liver tumor ablation procedures to treat 47 ICCs (May 2004 to January 2022). At initial diagnosis, 20 patients had Stage 1 or 2 disease and 5 had Stage 3 or 4 disease. Before ablation, 19 (76.0%) of the 25 patients had progressed through prior treatments, including resection (n = 11), chemotherapy (n = 11), transarterial embolization (n = 3), or radiotherapy (n = 1); 6 (24.0%) of the 25 patients were treatment naïve. Ablation modality selection was based on patient and tumor characteristics and operator preference. Primary outcomes included local progression–free survival (LPFS) and overall survival (OS) after ablation. Statistical analysis included Kaplan-Meier (KM) survival analyses and Cox proportional hazards models. ResultsThe mean ablated tumor size was 2.0 cm ± 1.2 (range, 0.5–5.0 cm). The 1-, 2-, and 5-year LPFS rates were 84.0% (95% CI, 72.9–96.8), 73.0% (95% CI, 59.0–90.4), and 59.5% (95% CI, 41.6–85.1), respectively. The 1-, 2-, and 5-year secondary LPFS rates were 89.5% (95% CI, 80.2–99.9), 81.9% (95% CI, 69.4–96.6), and 75.6% (95% CI, 60.2–94.9). The 1-, 2-, and 5-year LPFS rates for tumors ≤2 cm in size were all 95.8% (95% CI, 88.2–100.0). The 1-, 2-, and 5-year OS rates were 78.5% (95% CI, 63.5–97.2), 68.4% (95% CI, 51.3–91.1), and 43.5% (95% CI, 23.5–80.5). Larger tumor size was associated with decreased time to local progression (hazard ratio, 1.93; P = .012). ConclusionsPercutaneous ablation provided favorable intermediate to long-term disease control for patients with recurrent or inoperable cholangiocarcinoma.

Long-term efficacy of percutaneous transhepatic cholangioscopy-guided photodynamic therapy for postoperative recurrent extrahepatic cholangiocarcinoma

BackgroundCholangiocarcinoma recurs frequently following excision surgery and is usually inoperable, while radiotherapy, chemotherapy, and immunotherapy are of limited benefit. As palliative care, percutaneous transhepatic cholangial drainage (PTCD) can relieve biliary obstruction, prevent jaundice, and maintain quality of life (QOL), but does not improve overall survival. In contrast, photodynamic therapy (PDT) has been demonstrated to prolong the survival of inoperable cancer patients. ObjectiveThis study evaluated the clinical efficacy of percutaneous transhepatic cholangioscopy (PTCS)-guided PDT following PTCD versus PTCD alone for recurrent inoperable cholangiocarcinoma. MethodsThe case files of 39 patients with postoperative recurrence were retrospectively analyzed, including 18 receiving PTCS-guided PDT (PTCS-PDT group) and 21 receiving PTCD only as a control (PTCD group). Survival time was compared by Kaplan-Meier analysis and log-rank test, and QOL by the Functional Assessment of Cancer Therapy–Hepatobiliary (FACT-HEP) questionnaire. Clinicodemographic factors, including serum bilirubin and adverse reaction rates, were compared by Student's t-test or Fisher's exact test. The maximum follow-up period was 71 months. ResultsMedian survival time was significantly longer in the PTCS-PDT group than the PTCD group (23 months vs. 10 months, P = 0.00001). At 6 and 12 months post-treatment, total FACT-HEP score was lower in the PTCS-PDT group (P < 0.05), indicating improved QOL. There was no significant difference in total adverse events incidence between groups (19 [51.4%] vs. 15 [71.4%]; P = 0.131). ConclusionPTCS-guided PDT can prolong survival and improve the QOL of patients with postoperative cholangiocarcinoma recurrence without increasing complications. Significant and/or new findingsCompared to PTCD alone, PTCS-guided PDT significantly prolonged the survival time of patients with postoperative recurrent extrahepatic cholangiocarcinoma. Photodynamic therapy also improved patient quality of life by facilitating timely removal of the PTCD drainage tube. PTCS-guided PDT did not increase surgery-related complications except for skin phototoxicity, which can be easy avoided and treated.

Selective Internal Radiotherapy Changes the Immune Profiles of Extracellular Vesicles and Their Immune Origin in Patients with Inoperable Cholangiocarcinoma.

The incidence of cholangiocellular carcinoma (CCA) is rising worldwide. As there are no specific early symptoms or specific markers of CCA, it is often diagnosed in later inoperable stages. Accumulating evidence underlines the importance of radiation therapy in the induction of antitumor immunity. The surface protein composition on extracellular vesicles (EVs) relates to originating cells and thus may play a role in vesicle function. We assessed immune profiles of EVs and their immune origin in patients with inoperable CCA prior and after selective internal radiotherapy (SIRT). A total of 47 CCA patients receiving SIRT and 12 healthy volunteers (HV) were included. Blood was withdrawn before therapy (pre T) and after T. EVs were purified from plasma by cluster of differentiation (CD)9-, CD63-, and CD81-immunobead isolation. To detect differently abundant surface markers, dynamic range and EVs input quality were assessed. A total of 37 EVs surface markers were measured by flow cytometry and correlated either with the administered activity dose (MBq) or with the interval until death (month). EVs phenotyping identified lymphocytes, B cells, NK cells, platelets, endothelial cells, leukocyte activation, B cell activation, T and B cell adhesion markers, stem/progenitor cells, and antigen-presenting cells (APC) as EVs-parenteral cells. CD4 and CD8 significantly declined, while other markers significantly increased in CCA patients pre T vs. HV. Platelets-deriving EVs significantly decreased, normalizing to levels of HV but still significantly increasing vs. HV post SIRT. B cells-deriving EVs significantly increased pre T vs. HV, positively correlating with administered activity dose. MHCII and CD40 EVs significantly increased pre SIRT and negatively correlated with administered activity dose, while EVs from antigen presenting cells and CD49e pre SIRT positively correlated with survival time after therapy. Increased levels of CD24 and CD44 in cancer pre T were significantly decreased post T. Among the heterogeneity of EVs that was demonstrated, in particular, B cells-deriving, MHCII, and CD40 positive or APC-deriving EVs need to be further studied for their diagnostic or prognostic relevance in clinical scenarios.

Photochemical Internalization of Gemcitabine Is Safe and Effective in Locally Advanced Inoperable Cholangiocarcinoma.

BackgroundPhotochemical internalization (PCI) is a novel technology for light-induced enhancement of the local therapeutic effect of cancer drugs, utilizing a specially designed photosensitizing molecule (fimaporfin). The photosensitizing molecules are trapped in endosomes along with macromolecules or drugs. Photoactivation of fimaporfin disrupts the endosomal membranes so that drug molecules are released from endosomes inside cells and can reach their therapeutic target in the cell cytosol or nucleus. Compared with photodynamic therapy, the main cytotoxic effect with PCI is disruption of the endosomal membrane resulting in delivery of chemotherapy drug, and not to the photochemical reactions per se. In this study we investigated the effect of PCI with gemcitabine in patients with inoperable perihilar cholangiocarcinoma (CCA).MethodsThe in vitro cytotoxic effect of PCI with gemcitabine was studied on two CCA-derived cell lines. In a fimaporfin dose-escalation phase I clinical study, we administered PCI with gemcitabine in patients with perihilar CCA (n = 16) to establish a safe and tolerable fimaporfin dose and to get early signals of efficacy. The patients enrolled in the study had tumors in which the whole length of the tumor could be illuminated from the inside of the bile duct, using an optical fiber inserted via an endoscope (Fig. 1). Fimaporfin was administered intravenously at day 0; gemcitabine (i.v.) and intraluminal biliary endoscopic laser light application on day 4; followed by standard gemcitabine/cisplatin chemotherapy.ResultsPreclinical experiments showed that PCI enhanced the effect of gemcitabine. In patients with CCA, PCI with gemcitabine was well tolerated with no dose-limiting toxicities, and no unexpected safety signals. Disease control was achieved in 10 of 11 evaluable patients, with a clearly superior effect in the two highest dose groups. The objective response rate (ORR) was 42%, including two complete responses, while ORR at the highest dose was 60%. Progression-free survival at 6 months was 75%, and median overall survival (mOS) was 15.4 months, with 22.8 months at the highest fimaporfin dose.ConclusionPhotochemical internalization with gemcitabine was found to be safe and resulted in encouraging response and survival rates in patients with unresectable perihilar CCA.

A case of underwater endoscopic ultrasound guided abscess drainage

A 70-year-old male patient with inoperable cholangiocarcinoma was diagnosed with abdominal abscess. The oral antibiotics therapy did not have much effect on the abscess. Ultrasound findings also showed that percutaneous transhepatic abscess drainage was difficult. We then evaluated the feasibility of performing the endoscopic ultrasound (EUS) guided abscess drainage from the cardia of the stomach. Thus, we decided to perform EUS guided abscess drainage. When we inserted a 19-gauge needle into the EUS scope, the maximum bending angle of the EUS scope got too shallow to puncture the abscess. By filling the stomach with water, we were able to perform underwater EUS abscess drainage.

Endoscopic radiofrequency ablation for palliative treatment of hilar cholangiocarcinoma.

Background and AimsRecent data support a role for endoscopic radiofrequency ablation (RFA) in unresectable cholangiocarcinoma by improving stent patency and overall survival.MethodsWe describe 3 patients with inoperable cholangiocarcinoma with jaundice and cholestasis who were recommended palliative chemotherapy. They underwent endoscopic retrograde cholangiopancreatography with single-operator cholangioscope and intraductal RFA.ResultsThe procedures were performed without adverse events in all patients, with clinical and analytical improvement 1 month later.ConclusionsRFA is a promising and safe palliative treatment in patients with unresectable cholangiocarcinoma.

Unilateral versus bilateral hilar stents for the treatment of cholangiocarcinoma: a multicenter international study.

BackgroundEndoscopic placement of hilar stents is an accepted palliative therapy for patients with advanced, unresectable cholangiocarcinoma. However, whether unilateral versus bilateral stent placement provides optimal relief continues to be a subject of debate. The aim of this study was to compare the technical and clinical outcomes in patients with inoperable cholangiocarcinoma who received unilateral or bilateral self-expanding metal stents (SEMS).MethodsWe conducted a multicenter, international retrospective study of 187 patients with cholangiocarcinoma who received unilateral or bilateral SEMS. Outcomes included, but were not limited to, technical success, clinical success, adverse events, stent occlusion, and survival time. Results were further stratified based on the Bismuth classification.ResultsFifty patients received unilateral stents and 137 patients received bilateral stents. All patients achieved technical success. The clinical success rates were 86% for unilateral stents and 82.5% for bilateral stents (P>0.99). Clinical success was not statistically different for either group when stratified by the Bismuth classification (P=0.62 and P=0.72 respectively). There were significantly more adverse events in the bilateral stents group (11.7% vs. 0%, P=0.007). There was no greater risk of stent occlusion when bilateral stents were used (unadjusted P=0.71, adjusted P=0.81). There was a greater risk of death for patients who received bilateral SEMS (hazard ratio 1.78, 95% confidence interval 1.09-2.89; P=0.02).ConclusionsUnilateral and bilateral drainage had similar technical and clinical success rates. However, bilateral stents had a higher risk of death and more adverse events. Therefore, unilateral SEMS placement is sufficient for relief of biliary obstruction secondary to cholangiocarcinoma.

ASO Author Reflections: High-Dose Radiation Offers Local Control for Inoperable Intrahepatic Cholangiocarcinoma.

ASO Author Reflections: High-Dose Radiation Offers Local Control for Inoperable Intrahepatic Cholangiocarcinoma.

832TiP - Infigratinib versus gemcitabine plus cisplatin multicenter, open-label, randomized, phase III study in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: The PROOF trial

TPS4155Background: Cholangiocarcinoma is the most common biliary tract malignancy with approximately 5,000–10,000 new cases annually in the USA. The fibroblast growth factor receptor (FGFR) family ...

Acute kidney injury due to high-output external biliary drainage in a patient with malignant obstructive jaundice: a case report

BackgroundPersistent high output is a rare but potentially serious complication of percutaneous biliary drainage.Case presentationA 68-year-old Sinhalese woman with a palliative self-expanding metal stent placed for an inoperable hilar cholangiocarcinoma presented with worsening obstructive jaundice. Ultrasonography showed intrahepatic duct dilatation with the self-expanding metal stent in situ. Since this was indicative of a blocked stent, percutaneous transhepatic cholangiogram-guided internal biliary stenting through the self-expanding metal stent was attempted and failed. Therefore, an external biliary drain was left in the dilated biliary system. Post procedure, she developed a high biliary output of 3–4 liters per day and went into oliguric acute kidney injury with metabolic acidosis, most probably due to inadequate fluid replacement and hypovolemia.ConclusionAlthough the mechanism by which this occurs in some cases is unclear, early identification and prompt fluid resuscitation prevent acute kidney injury. The adoption of new strategies for internal drainage of long complex strictures will both prevent and ameliorate this problem.

Infigratinib versus gemcitabine plus cisplatin multicenter, open-label, randomized, phase 3 study in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: The PROOF trial.

TPS4155 Background: Cholangiocarcinoma is the most common biliary tract malignancy with approximately 5,000–10,000 new cases annually in the USA. The fibroblast growth factor receptor (FGFR) family plays an important role in cholangiocarcinoma, with FGFR2 gene fusions detected in about 15% of patients with cholangiocarcinoma. Infigratinib is an ATP-competitive, FGFR1–3-selective oral tyrosine kinase inhibitor. First-line treatment with chemotherapy offers only modest benefit and more effective treatment options are needed. Based on preliminary response data of infigratinib in relapsed/refractory cholangiocarcinoma with FGFR2 fusions/translocations (Phase 2 Study CBJG398X2204), the PROOF trial is evaluating infigratinib versus gemcitabine + cisplatin in front-line patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations. Methods: Patients with advanced/metastatic or inoperable cholangiocarcinoma are randomized 1:1 to oral infigratinib once daily for 21 days of a 28-day treatment cycle versus IV gemcitabine (1000 mg/m2) + cisplatin (25 mg/m2) on days 1 and 8 of a 21-day cycle. Treatment will continue until confirmed progressive disease by central review, intolerance, withdrawal of informed consent, or death. After 8 cycles of gemcitabine + cisplatin, patients can continue treatment if the investigator considers that they are deriving continued benefit. Patients on the gemcitabine + cisplatin arm who progress can cross-over to infigratinib. The primary endpoint is progression-free survival (PFS, per RECIST v1.1 central review). Secondary endpoints include overall survival, PFS (investigator determined), overall response rate, disease control rate, duration of response, and safety. Quality of life, PK and exploratory genetic alterations/biomarkers will also be measured. Current status: The study was initiated in February 2019 with planned enrollment of 350 patients with confirmed FGFR2 gene fusions/translocations. Clinical trial information: NCT03773302.

Liver transplantation for treatment of hilar cholangiocarcinoma with a report of three cases

Objective To investigate the feasibility of liver transplantation in the treatment of inoperable hilar cholangiocarcinoma. Methods The clinical data for 3 patients with unresectable hilar cholangiocarcinoma who underwent liver transplantation in the Department of Hepatobiliary Surgery of Fuzhou General Hospital of People′s Liberation Army from January 2006 to December 2012 were retrospectively analyzed. The patients were followed up by phone, outpatient service, and hospitalization. The starting point of the follow-up was the operation date. The patient's death was the end point. The clinical and pathological features, postoperative survival, tumor recurrence, and prognostic factors were observed. The follow-up deadline was December 2017. Results All 3 patients underwent classical orthotopic liver transplantation using retrograde perfusion through inferior vena cava and no perioperative deaths occurred. All 3 patients were followed up for 10 to 132 months. During the follow-up period, of 1 patient who died of tumor recurrence, the pathological TNM stage was T4aN1M0, and both had Union for International Cancer Control stage Ⅳa, and the tumor-free survival time was 3 months, and the survival time was 12 months. Of 1 patient who died of other causes, the pathological TNM stage was T3N1M0, and both had Union for International Cancer Control stage Ⅲ, and the tumor-free survival time was 12 months, and the survival time was 12 months. One case as of the end of follow-up, the patient has survived for 132 months, the pathological TNM staging was T2aN0M0, and both had Union for International Cancer Control stage Ⅱ. Conclusions Lymph node positive and high pathological TNM stage were poor prognosis factor for hilar cholangiocarcinoma who underwent liver transplantation. Patients with early hilar cholangiocarcinoma who don′t have lymph node metastasis are expected to benefit from liver transplantation. Key words: Liver transplantation; Bile duct neoplasms; Hilar cholangiocarcinoma

ROLE OF ADJUVANT DRUG THERAPY IN COMBINED TREATMENT FOR CHOLANGIOCELLULAR CARCINOMA

Cholangiocarcinoma (CC) is the second most common malignant disease of the liver. In recent decades various methods of treatment have been introduced. Nevertheless the number of treatment options for СС is still limited. Gemcitabine and cisplatin are the standard treatment for patients with inoperable CC. The second line of chemotherapy has not yet been standardized and depends on the interaction with first-line therapy. In addition many bile cancer studies to date cannot evaluate the differential activity of therapy of different anatomical localizations along the bile tract. There is no reliable evidence of the effectiveness of adjuvant therapy. The correlation of survival increase in patients with worse prognosis when using adjuvant therapy after surgical intervention seems to be reliable. The study of the molecular profile led to a more complex understanding of the genetic changes leading to clinically expressed malignant neoplasms and the possible future differentiation by anatomical or molecular structure would be optimal for the selection of chemotherapy.

Efficacy and Safety of Stereotactic Body Radiation Therapy for Treatment of Inoperable Intrahepatic and Perihilar Cholangiocarcinoma

Efficacy and Safety of Stereotactic Body Radiation Therapy for Treatment of Inoperable Intrahepatic and Perihilar Cholangiocarcinoma

Stereotactic ablative radiotherapy for patients with unresectable or medically inoperable cholangiocarcinoma.

The role of stereotactic ablative radiotherapy (SABR) in patients with unresectable or medically inoperable cholangiocarcinoma remains unclear. We examined the efficacy and safety of SABR in this group of patients. From January 2008 to December 2014, 15 patients with 17 lesions were included in this study. The lesions included 14 intrahepatic, 1 hilar, and 2 distal bile duct tumors. Three patients were classified as medically inoperable because of old age or multiple comorbidities. Tumors measured 0.8-13 cm (median, 3.6 cm). The median prescribed dose was 45 Gy delivered in 5 fractions over 5 consecutive days. The median follow-up period for surviving patients was 29.9 months. Objective responses were observed for 10 of 17 tumors (58.8%), including 3 complete responses (17.6%). The median survival duration was 12.6 months, and the 1- and 2-year overall survival rates were 50.3% and 14.4%, respectively. The 1- and 2-year in-field failure-free rates were 61.5% and 30.8%, respectively. For patients with biologically effective doses (BEDs) exceeding 75 Gy10, the 1- and 2-year overall survival rates were 58.3% and 33.3%, respectively, compared to 20.0% and 0%, respectively for those with BEDs lower than 75 Gy10. Radiation-induced liver disease did not develop in any patient. Acute toxicities were generally mild and tolerable. Stereotactic ablative radiotherapy could be an alternative treatment for unresectable or medically inoperable cholangiocarcinoma. Further dose escalation may be considered to optimize local control.

Prognostic impact of plasma CA 19-9, IL-6 and YKL-40 in patients with inoperable cholangiocarcinoma.

e15638Background: Cholangiocarcinoma (CCA) is associated with chronic inflammation. We tested the hypothesis, that serum CA 19-9 in combination with the pro-inflammatory biomarkers IL-6 and YKL-40 ...

Effect of ablative radiotherapy on survival in patients with inoperable intrahepatic cholangiocarcinoma: A dose response analysis.

294 Background: Advances in radiotherapy (RT) techniques and image guidance (IGRT) have enabled ablative doses to be delivered to large liver tumors. We evaluated the effects of RT dose escalation in the treatment of intrahepatic cholangiocarcinoma (IHCC). Methods: 79 consecutive patients with inoperable IHCC were treated between 2002–2014. Median tumor size 7.9 cm (range 2.2–17 cm), 57% had nodes+ and 20% had metastatic disease. 89% received gemcitabine and cisplatin before RT (35–100 Gy, median 58.05 Gy) for a median biologic equivalent dose (BED) of 80.5 Gy (range 43.75–180 Gy). 57% were treated with concurrent capecitabine. CT on rails IGRT with gating were used to deliver higher doses. Results: Median FU was 33 months (range 11–93 ). Median overall survival rate (OS) after diagnosis was 30 months; 1, 2, and 3-year OS rates were 87%, 61%, 44%. The median duration of local tumor control (LC) was 23 months; 1, 2, and 3-year LC rates were 81%, 45% and 27%. RT dose was the most important prognostic factor. Higher doses correlated with improved LC and OS. The 3-year OS for a BED greater than 80.5 was 73% versus 38% for those receiving lower doses (P =0.017). Similarly, 3-year LC was significantly higher (78% versus 45%, P= 0.04). On multivariate analysis, RT dose was significant for LC (P= 0.004) and OS (P= 0.006). The majority of patients (32/36, 89%) whose cause of death could be determined died from liver failure related to intrahepatic disease progression. Only 4 patients (11%) died from distant metastatic disease. There were no significant treatment related toxicities. Conclusions: Higher doses of RT improve LC and OS in inoperable IHCC. A BED &gt; 80.5 Gy appears to be ablative for large IHCCs. Long term survival rates compare favorably to resection. RT schedules that achieve a BED &gt; 80.5, such as 67.5 Gy in 15 fractions and 75 Gy in 25 fractions, should be used. Solutions for internal organ motion and IGRT are necessary for safe delivery of high doses near bowel. These findings support the use of 67.5 Gy in 15 fractions (BED = 97.88 Gy) in the current phase III NRG-GI001 randomized trial evaluating whether the addition of RT to chemotherapy affects survival for inoperable IHCC patients.

PWE-077 Outcome following resection of biliary cystadenoma – a single centre experience

<h3>Introduction</h3> Biliary cystadenoma (BCA) are rare, benign, potentially malignant cystic lesions of the liver, accounting for less than 5% of cystic liver tumours. These lesions have potential for recurrence and malignant transformation. The aim of the study was to analyse the outcome following resection of biliary cystadenoma from a single tertiary centre. <h3>Method</h3> Patients who had resection of BCA between 1993 and 2014 (21 years) were included in the study. The data were obtained form a prospectively maintained liver surgical and pathological database. Patient demographics, clinico-pathological characteristics, operative data and post-operative outcome were collected. <h3>Results</h3> 29 patients had surgery for BCA. Median age was 62 (IQ 48–74) years and the Male:Female ratio was 28:1. The main clinical presentation was abdominal pain (74%) followed by jaundice (20%), abdominal mass (14%) and deranged LFTs (3%). On pre-operative imaging, single cyst was seen in 76% of patients. The majority of cysts were found at central location (48%). Cyst characteristics included septations (48%), wall thickening (31%), wall irregularity (38%), papillary projections (10%) and mural nodule (3%). Surgical procedures performed as follows: atypical liver resection (45%), left hemihepatectomy (34%), right hemihepatectomy (10%), excision of extra hepatic bile duct (7%) and left lateral segmentectomy (3%). Three patients had de-roofing for suspected simple liver cyst, which were confirmed on histology as biliary cystadenoma. All had re-resection with clear margins. Median length of stay was 7 (IQ 6.5 – 8.5) days. 2 patients developed bile leak, one each managed conservatively and with ERCP. There was no peri-operative mortality. None of the patients had evidence of malignancy on final histology. Median follow-up was 11 (IQ 2–44) months. One patient developed delayed biliary stricture requiring reconstruction. One died 11 years later due to development of inoperable cholangiocarcinoma. <h3>Disclosure of interest</h3> None Declared. <h3>Conclusion</h3> Biliary cystadenomas can be resected safely with significantly low morbidity. Malignant transformation and recurrence are rare. Complete surgical resection provides a cure.