SEOM clinical guidelines for pancreatic and biliary tract cancer (2020)

AbstractPancreatic cancer (PC) and biliary tract cancer (BTC) are both aggressive and highly fatal malignancies. Nowadays we have a profound knowledge about the molecular landscape of these neoplasms and this has allowed new therapeutic options. Surgery is the only potentially curative therapy in both cancers, but disease recurrence is frequent. In PC, adjuvant treatment with mFOLFIRINOX has improved overall survival (OS) and in BTC adjuvant treatment with capecitabine seems to improve OS and relapse-free survival. Concomitant radio-chemotherapy could also be considered following R1 surgery in both neoplasms. Neoadjuvant treatment represents the best option for achieving an R0 resection in borderline PC. Upfront systemic chemotherapy is the treatment of choice in unresectable locally advanced PC and BTC; then locoregional therapy could be considered after an initial period of at least 3–4 months of systemic chemotherapy. In metastatic PC, FOLFIRINOX or Gemcitabine plus nab-paclitaxel have improved OS compared with gemcitabine alone. In metastatic BTC, cisplatin plus gemcitabine constitute the standard treatment. Progress in the knowledge of molecular biology has enabled the identification of new targets for therapy with encouraging results that could in the future improve the survival and quality of life of patients with PC and BTC.

Download Full-text

A pilot study of concurrent chemoradiotherapy with gemcitabine and cisplatin in patients with locally advanced biliary tract cancer

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-016-3143-2 ◽

2016 ◽

Vol 78 (4) ◽

pp. 841-846 ◽

Cited By ~ 6

Author(s):

Kyong Joo Lee ◽

Seung Woo Yi ◽

Jihye Cha ◽

Jinsil Seong ◽

Seungmin Bang ◽

...

Keyword(s):

Pilot Study ◽

Biliary Tract ◽

Biliary Tract Cancer ◽

Concurrent Chemoradiotherapy ◽

Locally Advanced ◽

Tract Cancer ◽

Gemcitabine And Cisplatin

Download Full-text

Dose-finding study using oxaliplatin (Ox) in combination with fixed dose gemcitabine (Gem) and radiotherapy (RT) in patients with locally advanced pancreatic or biliary tract cancer (PBCa)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.14028 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 14028-14028

Author(s):

M. Peeters ◽

T. Boterberg ◽

E. Monsaert ◽

I. Borbath ◽

A. Demols ◽

...

Keyword(s):

Pancreatic Cancer ◽

Biliary Tract ◽

Biliary Tract Cancer ◽

Locally Advanced ◽

Dose Finding ◽

Fixed Dose ◽

Karnofsky Performance Score ◽

Weekly Dose ◽

Tract Cancer ◽

Grade 3

14028 Background: Prognosis of inoperable PBCa is poor. Large randomized studies in pancreatic cancer showed a better survival in patients (pts) with locally advanced (LA) in comparison with metastatic disease. Data on radiochemotherapy are scarce in pts with LA disease. Therefore, we performed this multicenter, phase I study on the combination of radiotherapy and Gem/Ox. This regimen showed superior activity to Gem alone in pancreatic cancer (Louvet C et al. JCO 2005;23:3509–16.) Methods: After signed informed consent, pts with LA pancreatic cancer (n = 14) or biliary tract cancer (n=1) were included. They received two cycles of Gem/Ox1 followed by 5 weeks of RT (25 fractions of 1.8 Gy up to a total dose of 45 Gy) in combination with a weekly fixed dose of Gem (300 mg/m2 in 30’) and an escalating weekly dose of Ox (levels: 40/50/60 mg/m2). NCI-CTC 2.0 was used weekly to score treatment-related toxicity in all pts. Results: Today, 15 pts. with a median age of 61 y (range: 44–74), median Karnofsky performance score 90 (range: 70–100) and M/F = 8/7 were included. Upto 60 mg/m2 Ox, no disease limiting toxicity (DLT) occured. Grade 3 toxicity included nausea (n = 1), neutropenia (n = 3) and thrombocytopenia (n = 1). This latter patient was treated with 40 mg/m2 Ox and subsequently also experienced a grade 4. One patient receiving 50 mg/m2 Ox developed a grade 4 thrombocytopenia. Most frequent grade 1/2 toxicity was nausea (n = 8, 53%), thrombocytopenia (n = 5, 33%) and diarrhea (n = 5, 30%). Fourteen out of 15 received the full course of radiotherapy. Median time to progression (TTP) is 6.7 months (95% CI: 3.7–13.5). Thirteen out of 15 pts. are still alive. Conclusions: Combination of radiotherapy and Gemcitabin/Oxaliplatin in pts with LA pancreaticobiliairy cancer is feasible and well-tolerated. The long TTP underlines the potential activity of this regimen. As no DLT has been reached, we will use a dose of 60 mg/m2 Ox for further evaluation. [Table: see text]

Download Full-text

Incidence and risk factors for cholangitis during systemic chemotherapy among patients with advanced biliary tract cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.313 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 313-313 ◽

Cited By ~ 1

Author(s):

J. Hashimoto ◽

C. Morizane ◽

S. Kondo ◽

H. Ueno ◽

S. Mitsunaga ◽

...

Keyword(s):

Risk Factors ◽

Median Time ◽

Biliary Tract ◽

Biliary Tract Cancer ◽

Biliary Drainage ◽

Systemic Chemotherapy ◽

Sphincter Of Oddi ◽

Ampullary Cancer ◽

First Episode ◽

Tract Cancer

313 Background: Patients with biliary tract cancer (BTC) have a high risk of developing cholangitis. In patients with advanced BTC receiving systemic chemotherapy, cholangitis might interfere with the execution of the treatment. Furthermore, cholangitis during severe immunosuppression might develop into lethal complications such as sepsis or shock. Purpose: To determine the incidence of cholangitis among patients with advanced BTC undergoing systemic chemotherapy and to identify risk factors for the development of cholangitis. Methods: We reviewed the records of 301 patients with advanced BTC who received systemic chemotherapy at our hospital between February 2002 and July 2009. The clinical data of patients treated with gemcitabine monotherapy (GEM) as a first-line chemotherapy was retrieved. Results: One hundred and thirty-one patients were successfully followed up throughout the entire GEM treatment. Forty-three patients had intrahepatic BTC (32.8%), 28 had extrahepatic BTC (21.4%), 11 had hilar BTC (8.4%), 7 had ampullary cancer (5.3%), and 42 had gallbladder cancer (32.1%). Interventional radiological treatment or biliary reconstruction for biliary obstruction was performed in 50 patients (37.9%) prior to the start of chemotherapy. The median time to GEM treatment failure was 126 days. Cholangitis developed in 30 patients (22.9%) during GEM, and severe cholangitis developed in 10 patients (7.6%). The median time to the first episode of cholangitis from the start of chemotherapy was 65 days. Chemotherapy was discontinued because of cholangitis in 4 patients (3.1%), but no deaths as a result of cholangitis occurred. A multivariate analysis using a logistic regression model demonstrated that the presence of hilar obstruction (p=0.0002, OR: 10.748), the loss of sphincter of Oddi function (p=0.0005,OR: 8.960), and the presence of internal biliary drainage (p=0.007, OR: 4.472) were independent risk factors of cholangitis. Conclusions: The incidence of cholangitis during GEM treatment was 22.9% among the advanced BTC patients in this study. Hilar obstruction, the loss of sphincter of Oddi function, and internal biliary drainage may be risk factors of cholangitis. No significant financial relationships to disclose.

Download Full-text

Multicenter phase II study of docetaxel and oxaliplatin combination in patients with locally advanced or metastatic biliary tract cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.e15150 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. e15150-e15150

Author(s):

Eun-Kee Song ◽

Hye-Suk Han ◽

Ki Hyeong Lee ◽

Kyu Taek Lee ◽

Sang Byung Bae ◽

...

Keyword(s):

Biliary Tract ◽

Phase Ii ◽

Biliary Tract Cancer ◽

Phase Ii Study ◽

Locally Advanced ◽

Tract Cancer ◽

Multicenter Phase

Download Full-text

A phase II trial of regorafenib as a single agent in patients with advanced and metastatic biliary tract carcinoma and first-line chemotherapy failure.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.tps498 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. TPS498-TPS498

Author(s):

Anuj Kishor Patel ◽

Ronald G. Stoller ◽

John C. Rhee ◽

Barry C. Lembersky ◽

James Ohr ◽

...

Keyword(s):

Biliary Tract ◽

Phase Ii ◽

Biliary Tract Cancer ◽

Systemic Chemotherapy ◽

Single Agent ◽

Response To Treatment ◽

Mri Imaging ◽

First Line ◽

Tract Cancer ◽

Line Chemotherapy

TPS498 Background: Biliary tract cancers (including cholangiocarcinomas) are rare but aggressive malignancies with limited options for treatment. Currently, the combination of gemcitabine and cisplatin is considered the upfront systemic chemotherapy for patients with advanced and metastatic diseases. There is no ‘standard’ for second-line treatment. Several signaling pathways have been identified that might play a role in the development of biliary tract cancer and that may represent targets for directed therapies. Overexpression of VEGF and alterations of the Ras/Raf pathway have been identified in the majority of cholangiocarcinoma; some studies have shown these mutations to be associated with metastasis and poorer prognosis. Regorafenib is an oral multikinase inhibitor of multiple angiogenic and oncogenic kinases (VEGFR1-3, TIE2, PDGFR-β, FGFR1, KIT, RET, RAF) which has shown efficacy as a single agent in multiple solid tumors. This study evaluates the efficacy of regorafenib in patients with advanced/metastatic biliary tract cancer following the failure of first-line chemotherapy. Methods: Enrollment in this phase II, single-arm trial is ongoing. Eligible patients have unresectable advanced or metastatic biliary tract adenocarcinoma, and have failed first-line systemic chemotherapy. Patients receive regorafenib 120 mg orally daily in a 21 days on, 7 days off cycle. Tumor measurements take place every 3 cycles by CT or MRI imaging. Patients continue on therapy until disease progression or unacceptable toxicities. The primary end point of this study is median progression-free survival (PFS). To evaluate for evidence of activity, defined as a median PFS of 3.5 months or greater, with 83% power (one-sided test, α=0.10), target enrollment is 37 patients. Secondary endpoints include safety, overall response rate, disease control rate, median overall survival, and changes in biomarker levels. The correlation of these biomarkers and of tumor mutations with response to treatment is built into the study as well. As of September 2014, 9 patients had been enrolled. ClinicalTrials.gov Identifier: NCT02053376. Clinical trial information: NCT02053376.

Download Full-text

Genotyping of circulating tumor DNA in biliary tract cancer to reveal diagnostic and prognostic information.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.291 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 291-291 ◽

Cited By ~ 1

Author(s):

Andreas Wolfgang Berger ◽

Thomas Jens Ettrich ◽

Daniel Schwerdel ◽

Anna Dolnik ◽

Florian Beuter ◽

...

Keyword(s):

Biliary Tract ◽

Biliary Tract Cancer ◽

Palliative Treatment ◽

Tumor Tissue ◽

Locally Advanced ◽

Circulating Tumor Dna ◽

Imaging Data ◽

Tract Cancer ◽

Pretreated Patients ◽

Tumor Dna

291 Background: Biliary tract cancer (BTC) shows increasing incidence and is associated with a high mortality. Diagnosis is difficult due to the frequently occurring inaccessibility of the tumor for biopsy. Noninvasive approaches for (i) assessing and (ii) monitoring the tumor-specific molecular setup are desirable. Characterization of circulating tumor DNA (ctDNA) may help to achieve this goal. Methods: Blood and tumor tissue samples from patients with locally advanced or metastatic BTC prior to and during palliative treatment were collected. Tumor tissue and corresponding ctDNA samples underwent targeted genotyping of the 15 most frequently mutated genes in BTC. Findings were correlated with clinical and imaging data. Results: 24 therapy naive patients with histologically confirmed BTC were included for analyses. The overall mutational concordance (blood/tissue) was 74% and 92% for intrahepatic tumors. The mean variant allele frequency (VAF) in tumor tissue of therapy naïve patients was significantly higher compared to the respective ctDNA (p = 0.0291). In turn, the sequencing depth for ctDNA was significantly deeper (p = 0.0001), enabling us to detect also rare variants. Mean ctDNA VAF at baseline significantly correlated with tumor load (Spearman, r = 0.4073, p = 0.0433) and, exclusively for intrahepatic tumors, also with progression-free survival (Spearman, r = -0.5878, p = 0.0386). During 1st line palliative treatment, we detected a change in the mutational landscape in 36% of cases, Moreover, we had access to ctDNA samples of 5 pretreated patients. While ctDNA samples of therapy naïve patients (n = 23) showed a mean of 0.78 mutations per patient, ctDNA samples of pretreated patients (n = 5) exhibited a mean of 0.4 mutations (p = 0.5519). Conclusions: The molecular landscape of BTC is depicted in ctDNA which may enable to adapt diagnostic and therapeutic strategies to the specific molecular setup present at a certain time. In contrast, the use of targeted resequencing is likely to be insufficient for a comprehensive assessment of treatment induced BTC evolution. For this purpose, we suggest a more extensive analysis of ctDNA by broader sequencing applications and the incorporation of epigenetics.

Download Full-text