Intrahepatic cholangiocarcinoma hidden within cancer of unknown primary.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
08
12
2021
accepted:
06
04
2022
revised:
29
03
2022
pubmed:
29
4
2022
medline:
5
8
2022
entrez:
28
4
2022
Statut:
ppublish
Résumé
Many patients referred with a provisional diagnosis of cancer of unknown primary (pCUP) present with presumed metastatic disease to the liver. Due to the lack of definitive histological markers, intrahepatic cholangiocarcinoma (iCCA) may be overlooked. This study assessed the frequency of iCCA within a pCUP cohort. A single UK cancer-center study of sequential patients referred with pCUP from January 2017 to April 2020. Baseline diagnostic imaging was reviewed independently by a radiologist and oncologist; those with radiological features of iCCA (dominant liver lesion, capsular retraction) were identified. Of 228 patients referred with pCUP, 72 (32%) had malignancy involving the liver. 24/72 patients had radiological features consistent with iCCA; they were predominantly female (75%) with an average age of 63 years and 63% had an ECOG PS ≤ 2. The median overall survival (OS) of the iCCA group and the remaining liver-involved CUP group were similar (OS 4.1 vs 4.4 months, p-value = 0.805). Patients, where a primary diagnosis was subsequently determined, had better OS (10.2 months, p-values: iCCA = 0.0279: cCUP = 0.0230). In this study, 34% of patients with liver-involved pCUP, fulfilled the radiological criteria for an iCCA diagnosis. Consideration of an iCCA diagnosis in patients with CUP could improve timely diagnosis, molecular characterisation and treatment.
Sections du résumé
BACKGROUND
Many patients referred with a provisional diagnosis of cancer of unknown primary (pCUP) present with presumed metastatic disease to the liver. Due to the lack of definitive histological markers, intrahepatic cholangiocarcinoma (iCCA) may be overlooked. This study assessed the frequency of iCCA within a pCUP cohort.
METHODS
A single UK cancer-center study of sequential patients referred with pCUP from January 2017 to April 2020. Baseline diagnostic imaging was reviewed independently by a radiologist and oncologist; those with radiological features of iCCA (dominant liver lesion, capsular retraction) were identified.
RESULTS
Of 228 patients referred with pCUP, 72 (32%) had malignancy involving the liver. 24/72 patients had radiological features consistent with iCCA; they were predominantly female (75%) with an average age of 63 years and 63% had an ECOG PS ≤ 2. The median overall survival (OS) of the iCCA group and the remaining liver-involved CUP group were similar (OS 4.1 vs 4.4 months, p-value = 0.805). Patients, where a primary diagnosis was subsequently determined, had better OS (10.2 months, p-values: iCCA = 0.0279: cCUP = 0.0230).
CONCLUSIONS
In this study, 34% of patients with liver-involved pCUP, fulfilled the radiological criteria for an iCCA diagnosis. Consideration of an iCCA diagnosis in patients with CUP could improve timely diagnosis, molecular characterisation and treatment.
Identifiants
pubmed: 35484217
doi: 10.1038/s41416-022-01824-4
pii: 10.1038/s41416-022-01824-4
pmc: PMC9345855
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
531-540Informations de copyright
© 2022. The Author(s).
Références
CRUK. UK Cancer statistics [Internet]. UK Cancer statistics. 2018. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/cancer-of-unknown-primary
Varadhachary GR, Raber MN. Cancer of unknown primary site. N Engl J Med. 2014;371:757–65.
doi: 10.1056/NEJMra1303917
NICE. National Institute for Health and Clinical Excellence Metastatic malignant disease of unknown primary origin in adults: diagnosis and management (CG104). NICE; 2010.
Fizazi K, Greco FA, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v133–8.
doi: 10.1093/annonc/mdv305
Hainsworth JD, Fizazi K. Treatment for patients with unknown primary cancer and favorable prognostic factors. Semin Oncol. 2009;36:44–51.
doi: 10.1053/j.seminoncol.2008.10.006
Gatalica Z, Millis SZ, Vranic S, Bender R, Basu GD, Voss A, et al. Comprehensive tumor profiling identifies numerous biomarkers of drug response in cancers of unknown primary site: analysis of 1806 cases. Oncotarget. 2014;5:12440–7.
doi: 10.18632/oncotarget.2574
Ross JS, Wang K, Gay L, Otto GA, White E, Iwanik K, et al. Comprehensive genomic profiling of carcinoma of unknown primary site: new routes to targeted therapies. JAMA Oncol. 2015;1:40–9.
doi: 10.1001/jamaoncol.2014.216
Gatalica Z, Xiu J, Swensen J, Vranic S. Comprehensive analysis of cancers of unknown primary for the biomarkers of response to immune checkpoint blockade therapy. Eur J Cancer [Internet]. 2018;94:179–86. https://doi.org/10.1016/j.ejca.2018.02.021 .
doi: 10.1016/j.ejca.2018.02.021
Conway AM, Mitchell C, Kilgour E, Brady G, Dive C, Cook N. Molecular characterisation and liquid biomarkers in Carcinoma of Unknown Primary (CUP): taking the “U” out of “CUP.”. Br J Cancer. 2019;120:141–53.
doi: 10.1038/s41416-018-0332-2
Hainsworth JD, Rubin MS, Spigel DR, Boccia RV, Raby S, Quinn R, et al. Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: A prospective trial of the Sarah cannon research institute. J Clin Oncol. 2013;31:217–23.
doi: 10.1200/JCO.2012.43.3755
Yoon HH, Foster NR, Meyers JP, Steen PD, Visscher DW, Pillai R, et al. Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitacel and everolimus: NCCTG N0871 (alliance). Ann Oncol. 2016;27:339–44.
doi: 10.1093/annonc/mdv543
Hayashi H, Kurata T, Takiguchi Y, Arai M, Takeda K, Akiyoshi K, et al. Randomized phase II trial comparing site-specific treatment based on gene expression profiling with carboplatin and paclitaxel for patients with cancer of unknown primary site. J Clin Oncol. 2019;37:570–9.
doi: 10.1200/JCO.18.00771
Fizazi K, Maillard A, Penel N, Baciarello G, Allouache D, Daugaard G, et al. A phase III trial of empiric chemotherapy with cisplatin and gemcitabine or systemic treatment tailored by molecular gene expression analysis in patients with carcinomas of an unknown primary (CUP) site (GEFCAPI 04). Ann Oncol. 2019;30:v851.
doi: 10.1093/annonc/mdz394
Rassy E, Parent P, Lefort F, Boussios S, Baciarello G, Pavlidis N. New rising entities in cancer of unknown primary: Is there a real therapeutic benefit? Crit Rev Oncol Hematol. 2020;147:102882.
doi: 10.1016/j.critrevonc.2020.102882
Hainsworth JD, Schnabel CA, Erlander MG, Haines DW, Greco FA. A retrospective study of treatment outcomes in patients with carcinoma of unknown primary site and a colorectal cancer molecular profile. Clin Colorectal Cancer. 2012;11:112–8.
doi: 10.1016/j.clcc.2011.08.001
Varadhachary GR, Karanth S, Qiao W, Carlson HR, Raber MN, Hainsworth JD, et al. Carcinoma of unknown primary with gastrointestinal profile: Immunohistochemistry and survival data for this favorable subset. Int J Clin Oncol. 2014;19:479–84.
doi: 10.1007/s10147-013-0583-0
Saha SK, Zhu AX, Fuchs CS, Brooks GA. Forty‐year trends in cholangiocarcinoma incidence in the U.S.: intrahepatic disease on the rise. Oncologist. 2016;21:594–9.
doi: 10.1634/theoncologist.2015-0446
Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 2014;60:1268–89.
doi: 10.1016/j.jhep.2014.01.021
Rothwell DG, Ayub M, Cook N, Thistlethwaite F, Carter L, Dean E, et al. Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study. Nat Med. 2019;25:738–43.
Pauli C, Bochtler T, Mileshkin L, Baciarello G, Losa F, Ross JS, et al. A challenging task: identifying patients with Cancer of Unknown Primary (CUP) According to ESMO Guidelines: the CUPISCO trial experience. Oncologist. 2021;26:e769–79.
doi: 10.1002/onco.13744
Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013;31:1023–31.
doi: 10.1038/nbt.2696
Borger DR, Tanabe KK, Fan KC, Lopez HU, Fantin VR, Straley KS, et al. Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad‐based tumor genotyping. Oncologist. 2012;17:72–9.
doi: 10.1634/theoncologist.2011-0386
Arai Y, Totoki Y, Hosoda F, Shirota T, Hama N, Nakamura H, et al. Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology. 2014;59:1427–34.
doi: 10.1002/hep.26890
Graham RP, Barr Fritcher EG, Pestova E, Schulz J, Sitailo LA, Vasmatzis G, et al. Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. Hum Pathol. 2014;45:1630–8.
doi: 10.1016/j.humpath.2014.03.014
Simbolo M, Fassan M, Ruzzenente A, Mafficini A, Wood LD, Corbo V, et al. Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups. Oncotarget. 2014;5:2839–52.
doi: 10.18632/oncotarget.1943
Churi CR, Shroff R, Wang Y, Rashid A, Kang HSC, Weatherly J, et al. Mutation profiling in cholangiocarcinoma: prognostic and therapeutic implications. PLoS ONE. 2014;9:e115383.
Grassian AR, Pagliarini R, Chiang DY. Mutations of isocitrate dehydrogenase 1 and 2 in intrahepatic cholangiocarcinoma. Vol. 30, Curr Opin Gastroenterol. 2014;30:295–302.
Zhu AX, Borger DR, Kim Y, Cosgrove D, Ejaz A, Alexandrescu S, et al. Genomic profiling of intrahepatic cholangiocarcinoma: refining prognosis and identifying therapeutic targets. Ann Surg Oncol. 2014;21:3827–34.
doi: 10.1245/s10434-014-3828-x
Abou-Alfa GK, Macarulla Mercade T, Javle M, Kelley RK, Lubner S, Adeva J, et al. ClarIDHy: A global, phase III, randomized, double-blind study of ivosidenib (IVO) vs placebo in patients with advanced cholangiocarcinoma (CC) with an isocitrate dehydrogenase 1 (IDH1) mutation. Ann Oncol. 2019;30:v872–3.
doi: 10.1093/annonc/mdz394.027
Wainberg ZA, Lassen UN, Elez E, Italiano A, Curigliano G, De Braud FG, et al. Efficacy and safety of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600E–mutated biliary tract cancer (BTC): A cohort of the ROAR basket trial. J Clin Oncol. 2019;37:187–187.
doi: 10.1200/JCO.2019.37.4_suppl.187
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;21:671–84.
doi: 10.1016/S1470-2045(20)30109-1
Javle M, Roychowdhury S, Kelley RK, Sadeghi S, Macarulla T, Weiss KH, et al. Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study. Lancet Gastroenterol Hepatol. 2021;6:803–15.
doi: 10.1016/S2468-1253(21)00196-5
Ferrone CR, Ting DT, Shahid M, Konstantinidis IT, Sabbatino F, Goyal L, et al. The ability to diagnose intrahepatic cholangiocarcinoma definitively using novel branched DNA-enhanced albumin RNA in situ hybridization technology. Ann Surg Oncol. 2016;23:290–6.
doi: 10.1245/s10434-014-4247-8
Moran S, Martínez-Cardús A, Sayols S, Musulén E, Balañá C, Estival-Gonzalez A, et al. Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis. Lancet Oncol. 2016;17:1386–95.
doi: 10.1016/S1470-2045(16)30297-2
Lu MY, Chen TY, Williamson DFK, Zhao M, Shady M, Lipkova J, et al. AI-based pathology predicts origins for cancers of unknown primary. Nature. 2021;594:106–10.
doi: 10.1038/s41586-021-03512-4
Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–81.
doi: 10.1056/NEJMoa0908721
Javle M, Lowery M, Shroff RT, Weiss KH, Springfeld C, Borad MJ, et al. Phase II study of BGJ398 in patients with FGFR-Altered advanced cholangiocarcinoma. J Clin Oncol. 2018;36:276–82.
doi: 10.1200/JCO.2017.75.5009
Park JO, Feng Y-H, Chen Y-Y, Su W-C, Oh D-Y, Shen L, et al. Updated results of a phase IIa study to evaluate the clinical efficacy and safety of erdafitinib in Asian advanced cholangiocarcinoma (CCA) patients with FGFR alterations. J Clin Oncol. 2019;37:4117–4117.
doi: 10.1200/JCO.2019.37.15_suppl.4117
Tothill RW, Li J, Mileshkin L, Doig K, Siganakis T, Cowin P, et al. Massively-parallel sequencing assists the diagnosis and guided treatment of cancers of unknown primary. J Pathol. 2013;231:413–23.
doi: 10.1002/path.4251
Löffler H, Pfarr N, Kriegsmann M, Endris V, Hielscher T, Lohneis P, et al. Molecular driver alterations and their clinical relevance in cancer of unknown primary site. Oncotarget. 2016;7:44322–9.
doi: 10.18632/oncotarget.10035
Subbiah IM, Tsimberidou A, Subbiah V, Janku F. Next generation sequencing of carcinoma of unknown primary reveals novel combinatorial strategies in a heterogeneous mutational landscape. Oncoscience. 2017;4:47–56.
Kato S, Krishnamurthy N, Banks KC, De P, Williams K, Williams C, et al. Utility of genomic analysis in circulating tumor DNA from patients with carcinoma of unknown primary. Cancer Res. 2017;77:4238–46.
doi: 10.1158/0008-5472.CAN-17-0628