The features of peritoneal metastases from gastric cancer

Abstract

Peritoneal Carcinomatosis (PC) from metastasization of Gastric Cancer (GC), either present at first diagnosis of GC or as recurrence, is considered a fatal disease with no hope of definitive cure. Although newer agents like S1 and docetaxel have shown some promise, the median overall survival with the current first line chemotherapy is only 8 to 14 months, and is not greatly improved by adding targeted therapy. A multi-modal approach with cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed along the last two decades in order to tackle this problem. It’s an aggressive, combined treatment still under investigation. Studies coming from Europe and Far East reported long-term survival with 5-year survival rates up to nearly 25% in case of complete cytoreduction. Prophylactic/adjuvant setting is the most evidence-based indication for HIPEC in advanced-stage GC patients without PC, in order to prevent peritoneal recurrence and to improve overall survival. The rationale for immuno treatment in patients with gastric PC is strong. A randomized phase II study, combining complete CRS with intraperitoneal catumaxomab is on-going. The detection of free peritoneal cancer cells is the more realistic and practical way for the identification of patients at risk of carcinomatosis after surgery. The routine use of techniques of molecular detection in peritoneal washing appears to be the more sensitive method. Such patients are potential candidate for multimodal and locoregional treatments in order to prevent the peritoneal recurrence.

Keywords

Gastric cancer / peritoneal carcinomatosis / hyperthermic intraperitoneal chemotherapy / immunotherapy / reverse transcription-polymerase chain reaction

References

[1] Sadeghi B,Glehen O,Rivoire M,Fontaumard E,Caillot JL,Porcheron J,François Y,Gilly FN.Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study..Cancer2000;88:358-63

[2] Sugarbaker PH.Clinical pathway for the management of resectable gastric cancer with peritoneal seeding: best palliation with a ray of hope for cure..Oncology2000;58:96-107

[3] Thomassen I,van Ramshorst B,Bosscha K,Lemmens VE.Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors..Int J Cancer2014;134:622-8

[4] Yonemura Y,Kinoshita K,Takahashi S,Sasaki T.Effective therapy for peritoneal dissemination in gastric cancer..Surg Oncol Clin N Am2003;12:635-48

[5] Neuwirth MG,Karakousis GC.Then and now: cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), a historical perspective..J Gastrointest Oncol2016;7:18-28

[6] Yonemura Y,Kawamura T,Endo Y,Kiyosaki K.Cytoreduction and intraperitoneal chemotherapy for carcinomatosis from gastric cancer..Cancer Treat Res2007;134:357-73

[7] Lungoci C,Muntean V,Leebmann H,Piso P.Multimodality treatment strategies have changed prognosis of peritoneal metastases..World J Gastrointest Oncol2016;8:67-82 PMCID:PMC4714147

[8] Strieter RM.Chemokines: not just leukocyte chemoattractants in the promotion of cancer..Nat Immunol2001;2:285-6

[9] Geminder H,Goldberg L,Rechavi G,Ben-Baruch A.A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell-derived factor-1, in the development of bone marrow metastases in neuroblastoma..J Immunol2001;167:4747-57

[10] Jones D,Shahsafaei A.The chemokine receptor CXCR3 is expressed in a subset of B-cell lymphomas and is a marker of B-cell chronic lymphocytic leukemia..Blood2000;95:627-32

[11] Rempel SA,Ge S.Identification and localization of the cytokine SDF1 and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma..Clin Cancer Res2000;6:102-11

[12] Yasumoto K,Kawashima A,Arita Y,Minami T,Sakurai H,Yoshie O.Role of the CXCL12/CXCR4 axis in peritoneal carcinomatosis of gastric cancer..Cancer Res2006;66:2181-7

[13] Lee HJ.The role of the CXCR4/CXCL12 axis and its clinical implications in gastric cancer..Histol Histopathol2012;27:1155-61

[14] Bachelder RE,Mercurio AM.Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4..Cancer Res2002;62:7203-6

[15] Sugarbaker PH,Yonemura Y.Gastrectomy, peritonectomy, and perioperative intraperitoneal chemotherapy: the evaluation of treatment strategies for advanced gastric cancer..Semin Surg Oncol2003;21:233-48

[16] Mebius RE.Lymphoid organs for peritoneal cavity immune response: milky spots..Immunity2009;30:670-2

[17] Miao ZF,Zhao TT,Gao J,Xu HM.Peritoneal milky spots serve as a hypoxic niche and favor gastric cancer stem/progenitor cell peritoneal dissemination through hypoxia-inducible factor 1α..Stem Cells2014;32:3062-74 PMCID:PMC4282537

[18] Yonemura Y,Yamaguchi T,Obata T,Nojima N,Sasaki T.Mechanisms of the formation of the peritoneal dissemination in gastric cancer..Int J Oncol1996;8:795-802

[19] Chau I,Cunningham D,Oates J.Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer -- pooled analysis from three multicenter, randomized, controlled trials using individual patient data..J Clin Oncol2004;22:2395-403

[20] Kim JG,Park YH,Kim TY,Kang YK.Prognostic factors for survival of patients with advanced gastric cancer treated with cisplatin-based chemotherapy..Cancer Chemother Pharmacol2008;61:301-7

[21] Sakuramoto S,Yamaguchi T,Fujii M,Furukawa H,Ohashi Y,Higashino M,Kurita A.Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine..N Engl J Med2007;357:1810-20

[22] Bang YJ,Yang HK,Park YK,Lee KW,Noh SI,Mok YJ,Ji J,Button P,Noh SH.Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial..Lancet2012;379:315-21

[23] Cunningham D,Stenning SP,Van de Velde CJ,Scarffe JH,Falk SJ,Smith DB,Verma M,Chua YJ.Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer..N Engl J Med2006;355:11-20

[24] Ychou M,Pignon JP,Bouché O,Ducourtieux M,Fabre JM,Genève J,Rougier P.Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial..J Clin Oncol2011;29:1715-21

[25] Xiong BH,Ma L.An updated meta-analysis of randomized controlled trial assessing the effect of neoadjuvant chemotherapy in advanced gastric cancer..Cancer Invest2014;32:272-84

[26] Cao J,Liu T.Adjuvant chemotherapy after curative resection for gastric cancer: a meta-analysis..Scand J Gastroenterol2014;49:690-704

[27] Smalley SR,Haller DG,Estes NC,Gunderson LL,Martenson JA,Stemmermann GN,Macdonald JS.Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection..J Clin Oncol2012;30:2327-33 PMCID:PMC4517071

[28] Liang JW,Yu T,Zhang JJ.Is postoperative adjuvant chemoradiotherapy efficacious and safe for gastric cancer patients with D2 lymphadenectomy? A meta-analysis of the literature..Eur J Surg Oncol2014;40:1614-21

[29] Bilici A.Treatment options in patients with metastatic gastric cancer: current status and future perspectives..World J Gastroenterol2014;20:3905-15 PMCID:PMC3983446

[30] Van Cutsem E,Tjulandin S,Constenla M,Rodrigues A,Chao Y,Risse ML.Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group..J Clin Oncol2006;24:4991-7

[31] Koizumi W,Hara T,Akiya T,Miyashita K,Kobayashi O,Toh Y,Takagi S,Yanaoka K,Takeuchi M.S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial..Lancet Oncol2008;9:215-21

[32] Bang YJ,Feyereislova A,Shen L,Lordick F,Omuro Y,Aprile G,Hill J,Rüschoff J.Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial..Lancet2010;376:687-97

[33] Lordick F,Chung HC,Oh SC,Kurteva G,Moiseyenko VM,Park JO,Celik I,Melezínková H.Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial..Lancet Oncol2013;14:490-9

[34] Ross P,Cunningham D,Seymour M,Price T,Iveson T,Lofts F.Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer..J Clin Oncol2002;20:1996-2004

[35] Baba H,Endo K,Toh Y,Okamura T.Clinical efficacy of S-1 combined with cisplatin for advanced gastric cancer..Gastric Cancer2003;6 Suppl 1:45-9

[36] Jacquet P.Peritoneal-plasma barrier..Cancer Treat Res1996;82:53-63

[37] Tamura S,Okada K,Uji K,Suzuki R,Egawa C,Okamura S,Takatsuka Y.Pilot study of a combination of S-1 and paclitaxel for patients with peritoneal metastasis from gastric cancer..Gastric Cancer2010;13:101-8

[38] Ishizone S,Saito H,Sugiyama A,Miyagawa S.Efficacy of S-1 for patients with peritoneal metastasis of gastric cancer..Chemotherapy2006;52:301-7

[39] Sugarbaker PH.Peritonectomy procedures..Ann Surg1995;221:29-42

[40] Mura G,Garofalo A.Iascone C,Femia S.Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer: Indications and Technical Notes.Surgery in Multimodal Management of Gastric Cancer,2012;BerlinSpringer-Verlag107-12

[41] Giovanella BC,Morgan AC.Selective lethal effect of supranormal temperature on human neoplastic cells..Cancer Res1976;36:3944-50

[42] Wallner KE,Li GC.Hyperthermic enhancement of cell killing by mitomycin C in mitomycin C-resistent Chinese hamster ovary cells..Cancer Res1987;47:1308-12

[43] Gill RS,Nagendran J,Shi X,Schiller D.Treatment of gastric cancer with peritoneal carcinomatosis by cytoreductive surgery and HIPEC: a systematic review of survival, mortality, and morbidity..J Surg Oncol2011;104:692-8

[44] Glehen O,Cotte E,Osinsky D,François Y,Gilly FN.Cytoreductive surgery and intraperitoneal chemohyperthermia for peritoneal carcinomatosis arising from gastric cancer..Arch Surg2004;139:20-6

[45] Piso P,Popp F,Glockzin G.Safety of gastric resections during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis..Ann Surg Oncol2009;16:2188-94

[46] Mura G,Vagliasindi A,Tauceri F,Milandri C.Preliminary experience with hyperthermic intraperitoneal chemo-perfusion with oxaliplatin for the treatment of peritoneal carcinomatosis due to colorectal carcinoma..Chir Ital2007;59:217-23

[47] Fujimoto S,Kokubun M,Takahashi M,Kiuchi S,Miyoshi T.Intraperitoneal hyperthermic perfusion combined with surgery effective for gastric cancer patients with peritoneal seeding..Ann Surg1988;208:36-41 PMCID:PMC1493580

[48] Yonemura Y,Fushida S,Kamata T,Kosaka T,Miwa K.Hyperthermochemotherapy combined with cytoreductive surgery for treatment of gastric cancer with peritoneal dissemination..World J Surg1991;15:530-5

[49] Fujimoto S,Mutou T,Toyosawa T,Sumida M.Improved mortality rate of gastric carcinoma patients with peritoneal carcinomatosis treated with intraperitoneal hyperthermic chemoperfusion combined with surgery..Cancer1997;79:884-91

[50] Hirose K,Iida A,Nakagawara G,Kusaka Y.Efficacy of continuous hyperthermic peritoneal perfusion for the prophylaxis and treatment of peritoneal metastasis of advanced gastric cancer: evaluation by multivariate regression analysis..Oncology1999;57:106-14

[51] Hall JJ,Shen P,Douglas Case L,Geisinger KR.Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for advanced gastric cancer..J Gastrointest Surg2004;8:454-63

[52] Yonemura Y,Bandou E,Sawa T.Treatment of peritoneal dissemination from gastric cancer by peritonectomy and chemohyperthermic peritoneal perfusion..Br J Surg2005;92:370-5

[53] Scaringi S,Sabate JM,Jouet P,Parmentier G,Flamant Y.Advanced gastric cancer with or without peritoneal carcinomatosis treated with hyperthermic intraperitoneal chemotherapy: a single western center experience..Eur J Surg Oncol2008;34:1246-52

[54] Glehen O,Arvieux C,Boutitie F,Bereder JM,Quenet F.Peritoneal carcinomatosis from gastric cancer: a multi-institutional study of 159 patients treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy..Ann Surg Oncol2010;17:2370-7

[55] Yang XJ,Suo T,Yang GL,Zhou YF,Yonemura Y.Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial..Ann Surg Oncol2011;18:1575-81 PMCID:PMC3087875

[56] Magge D,Mavanur A,Ramalingam L,Zureikat A,Lee K,Pingpank J,Bartlett DL.Aggressive locoregional surgical therapy for gastric peritoneal carcinomatosis..Ann Surg Oncol2014;21:1448-55 PMCID:PMC4125004

[57] Rudloff U,Mullinax JE,Steinberg SM,Webb CC,Toomey MA,Pandalai P,Avital I.Impact of maximal cytoreductive surgery plus regional heated intraperitoneal chemotherapy (HIPEC) on outcome of patients with peritoneal carcinomatosis of gastric origin: results of the GYMSSA trial..J Surg Oncol2014;110:275-84

[58] Glehen O,Boutitie F,Quenet F,Mansvelt B,Msika S.Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1,290 patients..Cancer2010;116:5608-18

[59] Al-Shammaa HA,Yonemura Y.Current status and future strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis..World J Gastroenterol2008;14:1159-66 PMCID:PMC2690662

[60] Fujimoto S,Mutou T,Toyosawa T.Successful intraperitoneal hyperthermic chemoperfusion for the prevention of postoperative peritoneal recurrence in patients with advanced gastric carcinoma..Cancer1999;85:529-34

[61] Yonemura Y,Fujimura T,Katayama K,Sugiyama K,Kinoshita K,Sasaki T.Intraoperative chemohyperthermic peritoneal perfusion as an adjuvant to gastric cancer: final results of a randomized controlled study..Hepatogastroenterology2001;48:1776-82

[62] Yan TD,Sugarbaker PH,Yonemura Y,Morris DL.A systematic review and meta-analysis of the randomized controlled trials on adjuvant intraperitoneal chemotherapy for resectable gastric cancer..Ann Surg Oncol2007;14:2702-13

[63] Sun J,Wang Z,Chen X,Liang J.Benefits of hyperthermic intraperitoneal chemotherapy for patients with serosal invasion in gastric cancer: a meta-analysis of the randomized controlled trials..BMC Cancer2012;12:526 PMCID:PMC3551633

[64] Coccolini F,Glehen O,Poiasina E,Yonemura Y.Intraperitoneal chemotherapy in advanced gastric cancer. Meta-analysis of randomized trials..Eur J Surg Oncol2014;40:12-26

[65] Moehler M,Andus T,Arends J,Aust D,Baretton G,Boeing H,Bokemeyer C,Budach W,Caca K,Dietrich CF,Eickhoff A,Fahlke J,Fietkau R,Fleig W,Gabbert HE,Geissler M,Graeven U,Gross S,Heike M,Herbst B,Höcht S,Höfler H,Hölscher AH,Hübner J,Jakobs R,Kanzler S,Kiesslich R,Körber J,Kuhn C,Lang H,Lordick F,Lutz M,Malfertheiner P,Messmann H,Mönig S,Pistorius S,Rabenstein T,Ridwelski K,Roetzer I,Schepp W,Schmid RM,Schmiegel WH,Schuch G,Schütte K,Selgrad M,Seraphin J,Stahl M,Stoll C,Tannapfel A,Thuss-Patience P,Vanhoefer U,Vogelsang H,Wedding U,Wilke H,AWMF.German S3-guideline "Diagnosis and treatment of esophagogastric cancer"..Z Gastroenterol2011;49:461-531

[66] Glehen O,Villeneuve L,Bin-Dorel S,Piaton E.GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study..BMC Cancer2014;14:183 PMCID:PMC3995601

[67] Roviello F,Neri A.Treatment and prevention of peritoneal carcinomatosis from gastric cancer by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: overview and rationale..Eur J Surg Oncol2013;39:1309-16

[68] Canbay E,Brucher B,Sugarbaker PH.Intraperitoneal chemotherapy and its evolving role in management of gastric cancer with peritoneal metastases..Chin J Cancer Res2014;26:1-3

[69] Heiss MM,Koralewski P,Kolesnik OO,Dudnichenko AS,Razbadauskas A,Ganea-Motan E,Wimberger P,Schmalfeldt B,Bokemeyer C,Lahr A.The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial..Int J Cancer2010;127:2209-21 PMCID:PMC2958458

[70] Goéré D,Aupérin A,Mariette C,Zitvogel L.Treatment of gastric peritoneal carcinomatosis by combining complete surgical resection of lesions and intraperitoneal immunotherapy using catumaxomab..BMC Cancer2014;14:148 PMCID:PMC3973895

[71] Bando E,Takeshita Y,Yasui T,Fushida S,Nishimura G.Intraoperative lavage for cytological examination in 1,297 patients with gastric carcinoma..Am J Surg1999;178:256-62

[72] Makino T,Takiguchi S,Yamasaki M,Nishida T,Doki Y.The utility of pre-operative peritoneal lavage examination in serosa-invading gastric cancer patients..Surgery2010;148:96-102

[73] Roviello F,de Manzoni G,Di Leo A,De Stefano A.A prospective study of peritoneal recurrence after curative surgery for gastric cancer..Br J Surg2003;90:1113-9

[74] Bonenkamp JJ,Hermans J.Prognostic value of positive cytology findings from abdominal washings in patients with gastric cancer..Br J Surg1996;83:672-4

[75] Edge S.Cancer AJCo: AJCC cancer staging manual..7th ed. New York: Springer,2010;

[76] Allum WH,Griffin SM,Jankowski JA.Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, the British Society of Gastroenterology and the British Association of Surgical Oncology. Guidelines for the management of oesophageal and gastric cancer..Gut2011;60:1449-72

[77] Fujiwara Y,Taniguchi H,Takiguchi S,Yamasaki M.Genetic detection of free cancer cells in the peritoneal cavity of the patient with gastric cancer: present status and future perspectives..Gastric Cancer2007;10:197-204

[78] Katsuragi K,Sawada T,Ohira M.Prognostic impact of PCR-based identification of isolated tumor cells in the peritoneal lavage fluid of gastric cancer patients who underwent a curative R0 resection..Br J Cancer2007;97:550-6 PMCID:PMC2360343

[79] Wong J,Mittra A,Allen P,Coit D.Rt-PCR increases detection of submicroscopic peritoneal metastases in gastric cancer and has prognostic significance..J Gastrointest Surg2012;16:889-96

[80] Takata A,Fujiwara Y,Takahashi T,Miyata H,Takiguchi S,Doki Y.Prognostic value of CEA and CK20 mRNA in the peritoneal lavage fluid of patients undergoing curative surgery for gastric cancer..World J Surg2014;38:1107-11

[81] Takebayashi K,Yamamoto H,Yamaguchi T,Shimizu T,Sonoda H,Mekata E,Tani T.Surgery-induced peritoneal cancer cells in patients who have undergone curative gastrectomy for gastric cancer..Ann Surg Oncol2014;21:1991-7

[82] Nakabayashi K,Shibuya M,Tsujimoto M.Rapid detection of CEA mRNA in peritoneal washes using One-Step Nucleic acid Amplification (OSNA) for gastric cancer patients..Clin Chim Acta2015;439:137-42