Gemcitabine plus cisplatin versus chemoradiotherapy in locally advanced biliary tract cancer: Fédération Francophone de Cancérologie Digestive 9902 phase II randomised study

Phélip, Jean-Marc; Vendrely, V.; Rostain, Florian; Subtil, Fabien; Jouve, Jean-Louis; Gasmi, Mohamed; Michel, Pierre; Malicot, Karine Le; Smith, Denis; Seitz, Jean‐François; Fauchart, Jean-Pierre; Martin, Philippe; Bennouna, Jaafar; Morin, Thierry; Bonnet, Isabelle; Maingon, P.; Lepage, Côme; Chauffert, Bruno

doi:10.1016/j.ejca.2014.08.013

Cited by 49 publications

(40 citation statements)

References 18 publications

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“…Gemcitabine is a deoxycytidine analogue with antitumor activity and a key drug for chemotherapy of biliary tract cancer (25,26). To investigate the acquired chemoresistance of gallbladder cancer cells, GR subclones were established.…”

Section: Discussionmentioning

confidence: 99%

miR‑433 accelerates acquired chemoresistance of gallbladder cancer cells by targeting cyclin M

Zhang

et al. 2017

Oncol Lett

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Abstract. Resistance to chemotherapy is associated with dismal prognosis in patients with gallbladder cancer. Cyclin-dependent kinase 10 (CDK10) influences the chemosensitivity of gallbladder cancer cells, and cyclin M is the activating factor and binding partner of CDK10. To determine the effect of CDK10 or cyclin M overexpression on chemosensitivity, gemcitabine-resistant (GR) subclones were established from CDK10 or cyclin M stable transfectants. Stable overexpression of CDK10 increased the sensitivity to gemcitabine in non-resistant cells and did not further increase the sensitivity to gemcitabine in the GR subclones. GR subclones exhibited a significantly decreased expression of cyclin M while maintaining the expression levels of CDK10, compared with the non-resistant cells. MicroRNA (miR)-433 was identified as a candidate factor involved in the mechanism of the downregulation of M cyclin in GR subclones. Luciferase assays confirmed the interaction between miR-433 and the 3' untranslated region (3'UTR) of cyclin M. Additionally, ectopic expression of miR-433 significantly decreased the expression of cyclin M. Finally, increased expression of circulating miR-433 was associated with poor outcome of chemotherapy. The results of the present study suggest that miR-433 is a potential biomarker for evaluating chemosensitivity in gallbladder cancer. IntroductionGallbladder cancer is a relatively rare disease, with an estimated annual incidence of between 2 and 3 individuals/100,000; however, it is the most frequently encountered malignancy of the biliary tract (1,2). Complete surgical resection is the only potentially curative approach in early stages of the disease; however, the majority of cases are diagnosed in advanced stages. Additionally, because the aggressive malignancy tolerates traditional chemotherapy and radiotherapy, these cases have a dismal prognosis with an overall 5-year survival rate of <5% (3). Therefore, improving the diagnostic accuracy during the early stages and identifying the molecular mechanisms associated with chemotherapy or radiation resistance may provide a potential therapeutic approach for the treatment of gallbladder cancer.Cyclin M, also known as FAM58A, is a member of the cyclin family, which serves important regulatory functions in the cell cycle and transcription (4). Mutations in cyclin M cause toe syndactyly, telecanthus and anogenital and renal malformations syndrome, a human developmental anomaly (4,5). However, the function of cyclin M in other diseases remains unclear. Cyclin M has been identified as the binding partner for cyclin-dependent kinase 10 (CDK10) (5). CDK10 is involved in the regulation of cell division and function in various types of tumor (6-10). It was confirmed that CDK10 functions as a tumor suppressor gene and regulates the survivability of biliary tract cancer cells, including gallbladder cancer cells (8). These results suggest that cyclin M may also be involved in cancer development through binding to CDK10.MicroRNAs (miRNAs) are key negative regulator...

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Section: Discussionmentioning

confidence: 99%

miR‑433 accelerates acquired chemoresistance of gallbladder cancer cells by targeting cyclin M

Zhang

et al. 2017

Oncol Lett

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“…For example, patients treated with brachytherapy were more likely to be diagnosed before 2000, when suboptimal or antiquated chemotherapy regimens would have been used. The benefit of newer agents such as gemcitabine, or concurrent chemotherapy with 5-fluorouracil was not established until the early 2000s (29,30). Brachytherapy could also have been implemented to compensate for the lack of chemotherapy use due to either contraindication, intolerance, or both.…”

Section: Discussionmentioning

confidence: 99%

Comparison of external beam radiation and brachytherapy to external beam radiation alone for unresectable extrahepatic cholangiocarcinoma

Boothe

Hopkins

Frandsen

et al. 2016

J. Gastrointest. Oncol.

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Background: Extrahepatic cholangiocarcinoma (EHC) is a rare malignancy with a relatively poor prognosis. There are no randomized, prospective data to help define the optimal method of radiation delivery for unresectable EHC. The purpose of this study was to evaluate the benefit of adding brachytherapy to external beam radiation therapy (EBRT) for unresectable EHC. Methods: A retrospective review of 1,326 patients with unresectable EHC using the Surveillance, Epidemiology, and End Results (SEER) database was completed. Kaplan-Meier methods were used to analyze the primary endpoint, overall survival. Univariate and multivariate analysis was performed to identify and control for potential confounding variables, including age at diagnosis, sex, stage, grade, histology, race, year of diagnosis, and reason for no surgery. Results: Of the 1,326 patients with unresectable EHC, 1,188 (92.9%) received EBRT only, while 91 (7.1%) received both EBRT and brachytherapy. Patients receiving combined modality radiation therapy were more likely to be treated prior to the year 2000. Median overall survival for patients receiving EBRT and EBRT plus brachytherapy was 9 and 11 months, respectively (P=0.04). Cause specific survival was 12 months for those receiving EBRT only, and 15 months for those who received EBRT + brachytherapy (P=0.10). Survival analysis performed on patients with locoregional disease only revealed a trend towards prolonged overall survival with those receiving EBRT + brachytherapy (P=0.08). Multivariate analysis revealed grade and stage of disease were correlated with both overall survival and cause specific survival (P≤0.05).Conclusions: Among patients with unresectable EHC, the addition of brachytherapy to EBRT is associated with a prolonged median overall survival. However, the use of brachytherapy boost decreased in the last decade of the study.

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“…A phase II trial compared gemcitabine plus oxaliplatin vs chemoradiotherapy with 5-fluorouracil and cisplatin. The trial closed before completion due to slow recruitment, showing an increased median OS (19.9 mo vs 13.5 mo, HR 0.69) and progression free survival (11.0 mo vs 5.8 mo, HR 0.65) for the chemotherapy arm[ 126 ]. A small series using image-guided intensity-modulated radiation therapy both in gallbladder and extrahepatic bile ducts cancers demonstrated the feasibility of the procedure, allowing safe dose escalation[ 127 ].…”

Section: Treatmentmentioning

confidence: 99%

Practical review for diagnosis and clinical management of perihilar cholangiocarcinoma

Dondossola

Ghidini

Grossi

et al. 2020

WJG

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Cholangiocarcinoma (CCC) is the most aggressive malignant tumor of the biliary tract. Perihilar CCC (pCCC) is the most common CCC and is burdened by a complicated diagnostic iter and its anatomical location makes surgical approach burden by poor results. Besides its clinical presentation, a multimodal diagnostic approach should be carried on by a tertiary specialized center to avoid miss-diagnosis. Preoperative staging must consider the extent of liver resection to avoid post-surgical hepatic failure. During staging iter, magnetic resonance can obtain satisfactory cholangiographic images, while invasive techniques should be used if bile duct samples are needed. Consistently, to improve diagnostic potential, bile duct drainage is not necessary in jaundice, while it is indicated in refractory cholangitis or when liver hypertrophy is needed. Once resecability criteria are identified, the extent of liver resection is secondary to the longitudinal spread of CCC. While in the past type IV pCCC was not considered resectable, some authors reported good results after their treatment. Conversely, in selected unresectable cases, liver transplantation could be a valuable option. Adjuvant chemotherapy is the standard of care for resected patients, while neoadjuvant approach has growing evidences. If curative resection is not achieved, radiotherapy can be added to chemotherapy. This multistep curative iter must be carried on in specialized centers. Hence, the aim of this review is to highlight the main steps and pitfalls of the diagnostic and therapeutic approach to pCCC with a peculiar attention to type IV pCCC.

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Gemcitabine plus cisplatin versus chemoradiotherapy in locally advanced biliary tract cancer: Fédération Francophone de Cancérologie Digestive 9902 phase II randomised study

Cited by 49 publications

References 18 publications

miR‑433 accelerates acquired chemoresistance of gallbladder cancer cells by targeting cyclin M

miR‑433 accelerates acquired chemoresistance of gallbladder cancer cells by targeting cyclin M

Comparison of external beam radiation and brachytherapy to external beam radiation alone for unresectable extrahepatic cholangiocarcinoma

Practical review for diagnosis and clinical management of perihilar cholangiocarcinoma

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