Rimini M, Puzzoni M, Pedica F, Silvestris N, Fornaro L, Aprile G, et al. Cholangiocarcinoma: new perspectives for new horizons. Expert Rev Gastroenterol Hepatol. 2021;15(12):1367–83. https://doi.org/10.1080/17474124.2021.1991313.

Article  CAS  PubMed  Google Scholar 

Wu J, Yang S, Xu K, Ding C, Zhou Y, Fu X, et al. Patterns and trends of liver cancer incidence rates in Eastern and Southeastern Asian countries (1983–2007) and predictions to 2030. Gastroenterology. 2018;154(6):1719-1728.e5. https://doi.org/10.1053/j.gastro.2018.01.033.

Article  PubMed  Google Scholar 

Bertuccio P, Malvezzi M, Carioli G, Hashim D, Boffetta P, El-Serag HB, et al. Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma. J Hepatol. 2019;71(1):104–14. https://doi.org/10.1016/j.jhep.2019.03.013.

Article  PubMed  Google Scholar 

Sia D, Villanueva A, Friedman SL, Llovet JM. Liver cancer cell of origin, molecular class, and effects on patient prognosis. Gastroenterology. 2017;152:745–61.

Article  CAS  PubMed  Google Scholar 

Abou-Alfa GK, Sahai V, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21(5):671–84. https://doi.org/10.1016/S1470-2045(20)30109-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Goyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, et al. FOENIX-CCA2 study investigators. Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma. N Engl J Med. 2023;388(3):228–39. https://doi.org/10.1056/NEJMoa2206834.

Article  CAS  PubMed  Google Scholar 

Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(6):796–807. https://doi.org/10.1016/S1470-2045(20)30157-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhu AX, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, et al. final overall survival efficacy results of ivosidenib for patients with advanced cholangiocarcinoma with IDH1 mutation: the phase 3 randomized clinical ClarIDHy trial. JAMA Oncol. 2021;7(11):1669–77. https://doi.org/10.1001/jamaoncol.2021.3836.

Article  PubMed  Google Scholar 

Lamarca A, Kapacee Z, Breeze M, Bell C, Belcher D, Staiger H, et al. Molecular profiling in daily clinical practice: practicalities in advanced cholangiocarcinoma and other biliary tract cancers. J Clin Med. 2020;9(9):2854. https://doi.org/10.3390/jcm9092854.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rimini M, Loi E, Fabregat-Franco C, Burgio V, Lonardi S, Niger M, et al. Next-generation sequencing analysis of cholangiocarcinoma identifies distinct IDH1-mutated clusters. Eur J Cancer. 2022;175:299–310. https://doi.org/10.1016/j.ejca.2022.08.026.

Article  CAS  PubMed  Google Scholar 

Rimini M, Fabregat-Franco C, Burgio V, Lonardi S, Niger M, Scartozzi M, et al. Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma. Sci Rep. 2022;12(1):18775. https://doi.org/10.1038/s41598-022-22543-z.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rimini M, Macarulla T, Burgio V, Lonardi S, Niger M, Scartozzi M, et al. Gene mutational profile of BRCAness and clinical implication in predicting response to platinum-based chemotherapy in patients with intrahepatic cholangiocarcinoma. Eur J Cancer. 2022;171:232–41. https://doi.org/10.1016/j.ejca.2022.05.004.

Article  CAS  PubMed  Google Scholar 

Oh DY, He AR, Qin S, Chen LT, Okusaka T, Vogel A, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. NEJM Evid. 2022. https://doi.org/10.1056/EVIDoa2200015.

Article  PubMed  Google Scholar 

Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, et al. KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;401(10391):1853–65. https://doi.org/10.1016/S0140-6736(23)00727-4.

Article  PubMed  Google Scholar 

Rimini M, Fornaro L, Lonardi S, Niger M, Lavacchi D, Pressiani T, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: an early exploratory analysis of real-world data. Liver Int. 2023;43(8):1803–12. https://doi.org/10.1111/liv.15641.

Article  CAS  PubMed  Google Scholar 

Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–81. https://doi.org/10.1056/NEJMoa0908721.

Article  CAS  PubMed  Google Scholar 

Elias R, Giobbie-Hurder A, McCleary NJ, Ott P, Hodi FS, Rahma O. Efficacy of PD-1 & PD-L1 inhibitors in older adults: a meta-analysis. J Immunother Cancer. 2018;6(1):26. https://doi.org/10.1186/s40425-018-0336-8.

Article  PubMed  PubMed Central  Google Scholar 

Nishijima TF, Muss HB, Shachar SS, Moschos SJ. Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: a systematic review and meta-analysis. Cancer Treat Rev. 2016;45:30–7. https://doi.org/10.1016/j.ctrv.2016.02.006.

Article  CAS  PubMed  Google Scholar 

Nebhan CA, Cortellini A, Ma W, Ganta T, Song H, Ye F, et al. Clinical outcomes and toxic effects of single-agent immune checkpoint inhibitors among patients aged 80 years or older with cancer: a multicenter international cohort study. JAMA Oncol. 2021;7(12):1856–61. https://doi.org/10.1001/jamaoncol.2021.4960.

Article  PubMed  Google Scholar 

Vithayathil M, D’Alessio A, Fulgenzi CAM, Nishida N, Schönlein M, von Felden J, et al. Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. Liver Int. 2022;42(11):2538–47. https://doi.org/10.1111/liv.15405.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kugel CH 3rd, Douglass SM, Webster MR, Kaur A, Liu Q, Yin X, et al. Age correlates with response to anti-PD1, reflecting age-related differences in intratumoral effector and regulatory T-cell populations. Clin Cancer Res. 2018;24(21):5347–56. https://doi.org/10.1158/1078-0432.CCR-18-1116.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tang Q, Zhao S, Zhou N, He J, Zu L, Liu T, et al. PD-1/PD-L1 immune checkpoint inhibitors in neoadjuvant therapy for solid tumors (Review). Int J Oncol. 2023;62(4):49. https://doi.org/10.3892/ijo.2023.5497.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu J, Blake SJ, Yong MC, Harjunpää H, Ngiow SF, Takeda K, et al. Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease. Cancer Discov. 2016;6(12):1382–99. https://doi.org/10.1158/2159-8290.CD-16-0577.

Article  CAS  PubMed  Google Scholar 

Cascone T, Hamdi H, Zhang F, et al. Abstract 1719: Superior efficacy of neoadjuvant compared to adjuvant immune checkpoint blockade in non-small cell lung cancer. Cancer Res. 2018;78(13_Suppl):1719.

Article  Google Scholar 

Chaft JE, Rimner A, Weder W, Azzoli CG, Kris MG, Cascone T. Evolution of systemic therapy for stages I-III non-metastatic non-small-cell lung cancer. Nat Rev Clin Oncol. 2021;18(9):547–57. https://doi.org/10.1038/s41571-021-00501-4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Blank CU, Rozeman EA, Fanchi LF, Sikorska K, van de Wiel B, Kvistborg P, et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat Med. 2018;24(11):1655–61. https://doi.org/10.1038/s41591-018-0198-0.

Article  CAS  PubMed  Google Scholar 

Necchi A, Anichini A, Raggi D, Briganti A, Massa S, Lucianò R, et al. Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): an open-label, single-arm, phase II study. J Clin Oncol. 2018;36(34):3353–60. https://doi.org/10.1200/JCO.18.01148.

Article  CAS  PubMed  Google Scholar 

Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396(10257):1090–100. https://doi.org/10.1016/S0140-6736(20)31953-X.

Article  CAS  PubMed  Google Scholar 

Chalabi M, Fanchi LF, Dijkstra KK, Van den Berg JG, Aalbers AG, Sikorska K, et al. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med. 2020;26(4):566–76. https://doi.org/10.1038/s41591-020-0805-8.

Article  CAS  PubMed  Google Scholar 

Maithel SK, Keilson JM, Cao HST, Rupji M, Mahipal A, Lin BS, et al. NEO-GAP: a single-arm, phase II feasibility trial of neoadjuvant gemcitabine, cisplatin, and nab-paclitaxel for resectable, high-risk intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2023;30(11):6558–66. https://doi.org/10.1245/s10434-023-13809-5.

Article  PubMed  PubMed Central  Google Scholar 

Absenger G, Szkandera J, Pichler M, Stotz M, Arminger F, Weissmueller M, et al. A derived neutrophil to lymphocyte ratio predicts clinical outcome in stage II and III colon cancer patients. Br J Cancer. 2013;109(2):395–400. https://doi.org/10.1038/bjc.2013.346.

Article  CAS