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. 2021 Sep 15;13(18):4626.
doi: 10.3390/cancers13184626.

Risk Factors for Metachronous Isolated Peritoneal Metastasis after Preoperative Chemotherapy and Potentially Curative Gastric Cancer Resection: Results from the CRITICS Trial

Irene A Caspers  1   2 , Karolina Sikorska  3 , Astrid E Slagter  4 , Romy M van Amelsfoort  4 , Elma Meershoek-Klein Kranenbarg  5 , Cornelis J H van de Velde  6 , Pehr Lind  7   8 , Marianne Nordsmark  9 , Edwin P M Jansen  4 , Marcel Verheij  4   10 , Johanna W van Sandick  11 , Annemieke Cats  1 , Nicole C T van Grieken  2
Affiliations

Risk Factors for Metachronous Isolated Peritoneal Metastasis after Preoperative Chemotherapy and Potentially Curative Gastric Cancer Resection: Results from the CRITICS Trial

Irene A Caspers et al. Cancers (Basel). .

Abstract

Gastric cancer (GC) patients at high risk of developing peritoneal metastasis (PM) as a single site of metastasis after curative treatment may be candidates for adjuvant prophylactic strategies. Here we investigated risk factors for metachronous isolated PM in patients who were treated in the CRITICS trial (NCT00407186). Univariable and multivariable analyses on both metachronous isolated PM and 'other events', i.e., (concurrent) distant metastasis, locoregional recurrence or death, were performed using a competing risk model and summarized by cumulative incidences. Isolated PM occurred in 64 of the 606 (11%) included patients. Diffuse or mixed histological subtype, ypT4 tumor stage and LNhigh (ypN3 lymph node stage or a lymph node ratio >20%) were independent risk factors for isolated PM in both univariable and multivariable analyses. Likewise, LNhigh was an independent risk factor for 'other events'. Patients with tumors who were positive for all three independent risk factors had the highest two-year cumulative incidence of 43% for isolated PM development. In conclusion, diffuse or mixed histological subtype, ypT4 and LNhigh were identified as independent risk factors for isolated PM in patients treated with preoperative chemotherapy followed by surgical resection. The combination of these factors may identify a subgroup that may benefit from PM-preventing treatment strategies.

Keywords: gastric cancer; metachronous; multimodality treatment; peritoneal metastasis; risk factors.

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Conflict of interest statement

M.V. and A.C. have received grants from the Dutch Cancer Society, the Dutch Colorectal Cancer Group and Hoffmann La Roche. N.C.T.v.G. has received grants from the Dutch Cancer Society and The Netherlands Organization for Health Research and Development.

Figures

Figure 1
Figure 1
Flowchart of patients included in the CRITICS trial. PM: peritoneal metastasis; NEC: neuro-endocrine carcinoma.
Figure 2
Figure 2
Cumulative incidence plots of metachronous isolated peritoneal metastasis per risk factor. (a) Age; (b) Tumor localization; (c) Histological subtype according to Lauren classification; (d) Tumor stage; (e) Lymph node stage. GE-junction, gastroesophageal junction. LNhigh, ypN3 lymph node stage and/or a tumor positive lymph node ratio above 20%; LNlow, ypN0-2 and a tumor positive lymph node ratio below 20%.
Figure 2
Figure 2
Cumulative incidence plots of metachronous isolated peritoneal metastasis per risk factor. (a) Age; (b) Tumor localization; (c) Histological subtype according to Lauren classification; (d) Tumor stage; (e) Lymph node stage. GE-junction, gastroesophageal junction. LNhigh, ypN3 lymph node stage and/or a tumor positive lymph node ratio above 20%; LNlow, ypN0-2 and a tumor positive lymph node ratio below 20%.
Figure 3
Figure 3
Cumulative incidence plots of metachronous isolated peritoneal metastasis (red) and ‘other events’ (blue) in subgroups with different combinations of independent risk factors for isolated peritoneal metastasis. (a) ypT0-ypT3, LNlow intestinal GC (n = 183); (b) ypT0-ypT3, LNlow diffuse GC (n = 204); (c) ypT4, LNlow diffuse GC (n = 53); (d) ypT0-ypT3, LNhigh intestinal GC (n = 32); (e) ypT0-ypT3, LNhigh diffuse GC (n = 71); (f) ypT4, LNhigh diffuse GC (n = 40).
Figure 3
Figure 3
Cumulative incidence plots of metachronous isolated peritoneal metastasis (red) and ‘other events’ (blue) in subgroups with different combinations of independent risk factors for isolated peritoneal metastasis. (a) ypT0-ypT3, LNlow intestinal GC (n = 183); (b) ypT0-ypT3, LNlow diffuse GC (n = 204); (c) ypT4, LNlow diffuse GC (n = 53); (d) ypT0-ypT3, LNhigh intestinal GC (n = 32); (e) ypT0-ypT3, LNhigh diffuse GC (n = 71); (f) ypT4, LNhigh diffuse GC (n = 40).
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