SURGICAL TREATMENT AS AN INCREASE IN THE SURVIVAL OF PATIENTS WITH LIVER OLIGOMETASTASIS OF DUCTAL ADENOCARCINOMA OF THE PANCREAS. PATIENT SELECTION CRITERIA. REVIEW

The work is based on the analysis of the literature data on the problems of treating patients with metastatic pancreatic cancer, identifying a group of patients with more favorable treatment prognosis. The objectives of this review are to study diagnostic criteria, to determine the optimal algorithm for the diagnosis and treatment of patients with oligometastatic pancreatic disease. 
According to the Global Cancer Observatory (GLOBOCAN) in the world, in 2020 the incidence of pancreatic cancer among men and women was about 7.2 and 5.0 per 100 thousand, with a mortality rate of 6.7 and 4.6 %, respectively [1]. At the same time, in most cases, the disease is diagnosed at stage IIIIV, so the results of treatment remain unsatisfactory, 2/3 of patients die within 1 year after the diagnosis is made. The "gold standard" for the treatment of this group of patients today is only systemic antitumor therapy according to the FOLFRINOX regimen, in which the average overall survival is about 11.1 months. 
Thanks to the development of ideas about the mechanisms of tumor progression, the improvement of diagnostic methods and antitumor treatment, the concept of oligometastatic disease has appeared and is being actively studied. According to the current theory, this group of patients with stage IV tumors can potentially have a better prognosis. The analysis of modern domestic and foreign literature is carried out. According to scientific studies, careful selection and implementation of combined treatment can significantly increase the survival rate of this group of patients. Based on numerous studies, some authors have proposed optimal algorithms for the diagnosis and treatment of patients with oligometastatic pancreatic disease.

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209-249. http://doi.org/10.3322/caac.21660

2. Guy B. A brief history of cancer: Age-old milestones underlying our current knowledge database nt. J. Cancer. 2015; 136: 2022–2036. http://doi.org/10.1002/ijc.29134

3. Paget S. The distribution of secondary growths in cancer of the breast. Lancet. 1889; 133:571–573. https://doi.org/10.1016/S0140-6736(00)49915-0

4. Ewing G. Neoplastic Diseases: A Treatise on Tumours. 1928; 3: 1127. https://doi.org/10.1002/bjs.1800166126

5. Halsted W. The results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June, 1889 to January, 1894. Johns Hopkins Bull. 1894; 20(5): 497-555. http://doi.org/10.1097/00000658-189407000-00075

6. Halsted W. The results of radical operations for the cure of carcinoma of the breast. Ann Surg. 1907; 46:1-19. http://doi.org/10.1097/00000658-190707000-00001

7. Fisher B: Laboratory and clinical research in breast cancer-A personal adventure: The David A Karnovsky Memorial Lecture. Cancer Res. 1980; 40:3863-3874.

8. Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995; 13(1): 8-10. http://doi.org/10.1200/JCO.1995.13.1.8

9. Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, Dowell JE, Cheedella N, Nedzi L, Westover KD, Pulipparacharuvil S, Choy H, Timmerman RD. Consolidative radiotherapy for limited metastatic non-small-cell lung cancer: a phase 2 randomized clinical trial. JAMA Oncol. 2018; 4 (1). http://doi.org/10.1001/jamaoncol.2017.3501

10. Ruers T, Van Coevorden F, Punt CJ, Pierie JE, Borel- Rinkes I, Ledermann JA, Poston G, Bechstein W, Lentz MA, Mauer M, Folprecht G, Van Cutsem E, Ducreux M, Nordlinger B. Local treatment of unresectable colorectal liver metastases: results of a randomized phase II trial. J Natl Cancer Inst. 2017; 109 (9). http://doi.org/10.1093/jnci/djx015

11. Gomez DR, Tang C, Zhang J, Blumenschein GR Jr, Hernandez M, Lee JJ, Ye R, Palma DA, Louie AV, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Welsh JW, Gibbons DL, Karam JA, Kavanagh BD, Tsao AS, Sepesi B, Swisher SG, Heymach JV. Local consolidative therapy vs maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer: long-term results of a multi-institutional, phase II, randomized study. J Clin Oncol. 2019; 37:1558–65. http://doi.org/10.1200/JCO.19.00201

12. Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, Mulroy L, Lock M, Rodrigues GB, Yaremko BP, Schellenberg D, Ahmad B, Griffioen G, Senthi S, Swaminath A, Kopek N, Liu M, Moore K, Currie S, Bauman GS, Warner A, Senan S. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019; 393: 2051–58. http://doi.org/10.1016/S0140-6736(18)32487-5

13. Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, Lambert B, Delrue L, Bultijnck R, Claeys T, Goetghebeur E, Villeirs G, De Man K, Ameye F, Billiet I, Joniau S, Vanhaverbeke F, De Meerleer G. Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial. J Clin Oncol. 2018; 36: 446–53. http://doi.org/10.1200/JCO.2017.75.4853

14. Piciucchi M, Stigliano S, Archibugi L, Zerboni G, Signoretti M, Barucca V, Valente R, Fave GD, Capurso G. The neutrophil/ lymphocyte ratio at diagnosis is significantly associated with survival in metastatic pancreatic cancer patients. Int J MolSci. 2017;18(4):730. http://doi.org/10.3390/ijms18040730

15. Stevens L, Pathak S, Nunes QM, Pandanaboyana S, Macutkiewicz C, Smart N, Smith AM. Prognostic significance of pre-operative C-reactive protein and the neutrophillymphocyte ratio in resectable pancreatic cancer: Asystematic review. HPB (Oxford). 2015;17(4): 285–91. http://doi.org/10.1111/hpb.12355

16. Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa- Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011; 364(19): 1817–25. http://doi.org/10.1056/NEJMoa1011923

17. Frigerio I, Regi P, Giardino A, Scopelliti F, Girelli R, Bassi C, Gobbo S, Martini PT, Capelli P, D'Onofrio M, Malleo G, Maggino L, Viviani E, Butturini G. Downstaging in stage IV pancreatic cancer: a new population eligible for surgery? Ann Surg Oncol. 2017. 24: 2397–2403. http://doi.org/10.1245/s10434-017-5885-4

18. Tempero MA, Malafa MP, Al-Hawary M, Asbun H, Bain A, Behrman SW, Benson AB 3rd, Binder E, Cardin DB, Cha C, Chiorean EG, Chung V, Czito B, Dillhoff M, Dotan E, Ferrone CR, Hardacre J, Hawkins WG, Herman J, Ko AH, Komanduri S, Koong A, LoConte N, Lowy AM, Moravek C, Nakakura EK, O'Reilly EM, Obando J, Reddy S, Scaife C, Thayer S, Weekes CD, Wolff RA, Wolpin BM, Burns J, Darlow S. Pancreatic adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017; 15(8): 1028–61. http://doi.org/10.6004/jnccn.2017.0131

19. Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goéré D, Seufferlein T, Haustermans K, Van Laethem JL, Conroy T, Arnold D. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26(Suppl 5): 56– 68. http://doi.org/10.1093/annonc/mdv295

20. Казаков А.Д., Соловьева Т.С. Факторы риска несостоятельности панкреатодигестивного анастомоза после панкреатодуоденальной резекции. Известия Российской Военно-медицинской академии. 2019; 1(1): 187-190. [Kazakov A.D., Solovieva T.S. Risk factors of failure pancreatodigestive anastomosis after pancreatoduodenectomy. Izvestia of the Russian Military Medical Academy. 2019; 1(1): 187-190. (In Russ.)]

21. Котив Б.Н., Дзидзава И.И., Смородский А.В. Гастропанкреатодуоденальная резекция при погранично резектабельном раке поджелудочной железы. Сборник научных работ III Петербургского международного онкологического форума "Белые ночи 2017". 2017; 216-217. [Kotiv B.N., Dzidzava I.I., Smorodsky A.V. Gastropancreatoduodenal resection for borderline resectable pancreatic cancer. Collection of scientific papers of the III St. Petersburg International Oncological Forum "White Nights 2017". 2017; 216-217. (In Russ.)]

22. Park, J.B.; Kim, Y.H.; Kim, J.; Chang, H.M.; Kim, T.W.; Kim, S.C.; Kim, P.N.; Han, D.J. Radiofrequency ablation of liver metastasis in patients with locally controlled pancreatic ductal adenocarcinoma. J. Vasc. Interv. Radiol. 2012; 23: 635– 641. http://doi.org/10.1016/j.jvir.2012.01.080

23. Нартайлаков М.А., Галимов И.И., Шакуров Д.Ф., Логинов М.О., Мирасова Г.Х. Эффективность рентгенэндоваскулярной эмболизации ветви воротной вены при обширных резекциях печени. Хирургическая практика. 2022;(1):33-37. https://doi.org/10.38181/2223-2427-2022-1-33-37 [Nartailakov M.A., Galimov I.I., Shakurov D.F., Loginov M.O., Mirasova G.K. Efficiency portal vein x-ray vascular embolization in extended hepatic resection. Surgical practice. 2022;(1):33-37. (In Russ.) https://doi.org/10.38181/2223-2427-2022-1-33-37]

24. Шостка К. Г., Кузнецов И. М., Арутюнян К. В., Ильин К. С., Кучеренко А. Д., Фёдоров К.С. Выбор лечебной тактики при раке поджелудочной железы с синхронными метастазами в легкие. Вестник хирургии им. И. И. Грекова. 2018; 178(3): 94. [Shostka K. G., Kuznetsov I. M., Arutyunyan K. V., Ilyin K. S., Kucherenko A. D., Fedorov K. S. The choice of treatment tactics for pancreatic cancer with synchronous lung metastases. Bulletin of Surgery. I. I. Grekova. 2018; 178(3): 94. (In Russ.)]

25. Шостка К.Г., Кузнецов И.М., Арутюнян К.В., Ильин К.С., Кучеренко А.Д., Федоров К.С. Рак поджелудочной железы с синхронными метастазами в легкие Вестник национального медико-хирургического центра им. Н.И.Пирогова. 2018; 13(2): 166-169. [Shostka K.G., Kuznetsov I.M., Arutyunyan K.V., Ilyin K.S., Kucherenko A.D., Fedorov K.S. Pancreatic cancer with synchronous lung metastases. Bulletin of the National Medical and Surgical Center. N.I. Pirogov. 2018; 13(2): 166-169. (In Russ.)]

26. Zhao Y, Li J, Li D, Wang Z, Zhao J, Wu X, Sun Q, Lin PP, Plum P, Damanakis A, Gebauer F, Zhou M, Zhang Z, Schlösser H, Jauch KW, Nelson PJ, Bruns CJ. Tumor biology and multidisciplinary strategies of oligometastasis in gastrointestinal cancers. Semin Cancer Biol. 2020; 60: 334-343. http://doi.org/10.1016/j.semcancer.2019.08.026

27. Нартайлаков М.А., Галимов И.И., Шакуров Д.Ф., Логинов М.О., Мирасова Г.Х. Эффективность рентгенэндоваскулярной эмболизации ветви воротной вены при обширных резекциях печени. Хирургическая практика. 2022;(1):33-37. https://doi.org/10.38181/2223-2427-2022-1-33-37[Nartailakov M.A., Galimov I.I., Shakurov D.F., Loginov M.O., Mirasova G.K. efficiency portal vein x-ray vascular embolization in extended hepatic resection. Surgical practice. 2022;(1):33-37. (In Russ.) https://doi.org/10.38181/2223-2427-2022-1-33-37]

28. Hackert T, Niesen W, Hinz U, Tjaden C, Strobel O, Ulrich A, Michalski CW, Büchler MW. Radical surgery of oligometastatic pancreatic cancer. Eur J Surg Oncol. 2017; 43(2): 358–363. http://doi.org/10.1016/j.ejso.2016.10.023

29. Yang J, Zhang J, Lui W, Huo Y, Fu X, Yang M, Hua R, Wang L, Sun Y. Patients with hepatic oligometastatic pancreatic body/tail ductal adenocarcinoma may benefit from synchronous resection. HPB (Oxford). 2020; 22(1): 91-101 https://doi.org/10.1016/j.hpb.2019.05.015

30. Tachezy M, Gebauer F, Janot M, Uhl W, Zerbi A, Montorsi M, Perinel J, Adham M, Dervenis C, Agalianos C, Malleo G, Maggino L, Stein A, Izbicki JR, Bockhorn M. Synchronous resections of hepatic oligometastatic pancreatic cancer: Disputing a principle in a time of safe pancreatic operations in a retrospective multicenter analysis. Surgery. 2016; 160(1): 136-144. https://doi.org/10.1016/j.surg.2016.02.019

31. Crippa S, Bittoni A, Sebastiani E, Partelli S, Zanon S, Lanese A, Andrikou K, Muffatti F, Balzano G, Reni M, Cascinu S, Falconi M. Is there a role for surgical resection in patients with pancreatic cancer with liver metastases responding to chemotherapy? Eur J Surg Oncol. 2016. 42: 1533–1539. http://doi.org/10.1016/j.ejso.2016.06.398

32. Ghaffarpasand E., Barrows C., Callery M.P., Moser A.J., Kent T.S. Resection of oligometastatic pancreatic ductal adenocarcinoma: a systematic review and meta-analysis. HBP. 2019; 21(1): 83-87. https://doi.org/10.1016/j.hpb.2019.03.138

33. Kandel P, Wallace MB, Stauffer J, Bolan C, Raimondo M, Woodward TA, Gomez V, Ritter AW, Asbun H, Mody K. Survival of Patients with Oligometastatic Pancreatic Ductal Adenocarcinoma Treated with Combined Modality Treatment Including Surgical Resection: A Pilot Study. Journal of Pancreatic Cancer. 2018; 4(1): 88-94. https://doi.org/10.1089/pancan.2018.0011

34. Hua Y, Wang P, Zhu X, Shen Y, Wang K, Shi W, Lin J, Meng Z, Chen Z., Chen H. Radiofrequency ablation for hepatic oligometastatic pancreatic cancer: An analysis of safety and efficacy. Pancreatology. 2017; 17: 967–973. https://doi.org/10.1016/j.pan.2017.08.072

35. Haas M, Heinemann V, Kullmann F, Laubender R, Klose C, Bruns C, Holdenrieder S, Modest D, Schulz C, Boeck S. Prognostic value of CA 19-9, CEA, CRP, LDH and bilirubin levels in locally advanced and metastatic pancreatic cancer: Results from a multicenter, pooled analysis of patients receiving palliative chemotherapy. J Cancer Res Clin Oncol. 2013; 139(4): 681–689. https://doi.org/10.1007/s00432-012-1371-3

36. Boeck S, Wittwer C, Heinemann V, Haas M, Kern C, Stieber P, Nagel D, Holdenrieder S. Cytokeratin 19- fragments (CYFRA 21-1) as a novel serum biomarker for response and survival in patients with advanced pancreatic cancer. Br J Cancer. 2013; 108(8): 1684–1694. https://doi.org/10.1038/bjc.2013.158

37. Song J, Chen M, Guo J, Lian S, Xu B. Combined pretreatment serum CA19- 9 and neutrophil-to-lymphocyte ratio as a potential prognostic factor in metastatic pancreatic cancer patients. Medicine (Baltimore). 2018; 97(4). https://doi.org/10.1097/MD.0000000000009707

38. Hang J, Wu L, Zhu L, Sun Z, Wang G, Pan J, Zheng S, Xu K, Du J, Jiang H. Prediction of overall survival for metastatic pancreatic cancer: Development and validation of a prognostic nomogram with data from open clinical trial and real-world study. Cancer Med. 2018; 7(7): 2974–2984. https://doi.org/10.1002/cam4.1573

39. Kim H, Lee J, Paik K, Lee Y, Hwang J, Kim J. Initial metastatic site as aprognostic factor in patients with stage IV pancreatic ductal adenocarcinoma. Medicine (Baltimore). 2015; 94(25). https://doi.org/10.1097/MD.0000000000001012

40. Uppal A, Wightman S, Mallon S, Oshima G, Pitroda S, Zhang Q, Huang X, Darga T, Huang L, Andrade J, Liu H, Ferguson M, Greene G, Posner M, Hellman S, Khodarev N, Weichselbaum R. 14q32-encoded microRNAs mediate an oligometastatic phenotype. Oncotarget. 2015; 6: 3540–3552. https://doi.org/10.18632/oncotarget.2920

41. Lussier Y, Khodarev N, Regan K, Corbin K, Li H, Ganai S, Khan S, Gnerlich J, Darga T, Fan H, Karpenko O, Paty P, Posner M, Chmura S, Hellman S, Ferguson M, Weichselbaum R. Oligo- and polymetastatic progression in lung metastasis(es) patients is associated with specific microRNAs. PLoS One. 2012; 7(12). https://doi.org/10.1371/journal.pone.0050141

42. Oshima G, Poli E, Bolt M, Chlenski A, Forde M, Jutzy J, Biyani N, Posner M, Pitroda S, Weichselbaum R, Khodarev N. DNA Methylation Controls Metastasis-Suppressive 14q32- Encoded miRNAs. Cancer Res. 2019; 79(3): 650-662. https://doi.org/10.1158/0008-5472

43. deSouza N, Liu Y, Chiti A, Oprea-Lager D, Gebhart G, Van Beers B, Herrmann K, Lecouvet F. Strategies and technical challenges for imaging oligometastatic disease: Recommendations from the European Organisation for Research and Treatment of Cancer imaging group. Eur J Cancer. 2018; 91: 153-163. https://doi.org/10.1016/j.ejca.2017.12.012

44. Guckenberger M, Lievens Y, Bouma A, Collette L, Dekker A, deSouza N, Dingemans A, Fournier B, Hurkmans C, Lecouvet F, Meattini I, Méndez Romero A, Ricardi U, Russell N, Schanne D, Scorsetti M, Tombal B, Verellen D, Verfaillie C, Ost P. Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation. Lancet Oncol. 2020; 21(1): 18-28. https://doi.org/10.1016/S1470-2045(19)30718-1

45. Damanakis A, Ostertag L, Waldschmidt D, Kütting F, Quaas A, Plum P, Bruns C, Gebauer F, Popp F. Proposal for a definition of "Oligometastatic disease in pancreatic cancer". BMC Cancer. 2019; 19(1): 1261. https://doi.org/10.1186/s12885-019-6448-9

46. Niesen W, Primavesi F, Gasteiger S, Neoptolemos J, Hackert T, Stättner S. Surgical and local therapeutic concepts of oligometastatic pancreatic cancer in the era of effective chemotherapy. European Surgery. 2019; 51: 153–164, https://doi.org/10.1007/s10353-019-0589-6

47. Wei M, Shi S, Hua J, Xu J, Yu X. Simultaneous resection of the primary tumour and liver metastases after conversion chemotherapy versus standard therapy in pancreatic cancer with liver oligometastasis: protocol of a multicenter, prospective, randomised phase III control trial (CSPAC-1). BMJ Open 2019; 9. https://doi.org/10.1136/bmjopen-2019-033452