Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases

被引：7

作者：

Tonello, M. ^{[1
]}

Baratti, D. ^{[2
]}

Sammartino, P. ^{[3
]}

Di Giorgio, A. ^{[4
]}

Robella, M. ^{[5
]}

Sassaroli, C. ^{[6
]}

Framarini, M. ^{[7
]}

Valle, M. ^{[8
]}

Macri, A. ^{[9
]}

Graziosi, L. ^{[10
]}

Coccolini, F. ^{[1
,2
,11
,12
]}

Lippolis, P., V ^{[13
]}

Gelmini, R. ^{[1
,4
,14
]}

Deraco, M. ^{[2
]}

Biacchi, D. ^{[3
]}

Aulicino, M. ^{[4
]}

Vaira, M. ^{[5
]}

De Franciscis, S. ^{[1
,5
,15
]}

Acapito, F. ^{[7
,8
]}

Carboni, F.

Milone, E. ^{[9
]}

Donini, A. ^{[10
]}

Fugazzola, P. ^{[16
]}

Faviana, P. ^{[17
]}

Sorrentino, L. ^{[14
]}

Pizzolato, E. ^{[1
]}

Cenzi, C. ^{[18
]}

Del Bianco, P. ^{[18
]}

Sommariva, A. ^{[1
]}

机构：

[1] Veneto Inst Oncol IOV IRCCS, Unit Surg Oncol Esophagus & Digest Tract, Via Carpani,16, I-31033 Padua, Italy

[2] Fdn IRCCS Ist Nazl Tumori, Dept Surg, Peritoneal Surface Malignancy Unit, Milan, Italy

[3] Sapienza Univ Rome, Cytoreduct Surg & HIPEC Unit, Dept Surg Pietro Valdoni, Rome, Italy

[4] Fdn Policlin Univ A Gemelli, Surg Unit Peritoneum & Retroperitoneum, Rome, Italy

[5] Candiolo Canc Inst, Surg Oncol Unit, FPO IRCCS, Turin, Italy

[6] Ist Nazl Studio & Cura Tumori Fdn Pascale IRCCS, Abdominal Oncol Dept, Naples, Italy

[7] AUSL Romagna, Morgagni Pierantoni Hosp, Gen & Oncol Dept Surg, Forli, Italy

[8] Regina Elena Inst Canc Res, Peritoneal Tumours Unit, IRCCS, Rome, Italy

[9] Univ Hosp G Martino, Peritoneal & Retroperitonel Surg Unit, Messina, Italy

[10] Univ Perugia, Santa Maria Misericordia Hosp, Gen & Emergency Surg Dept, Perugia, Italy

[11] Bufalini Hosp, Gen Emergency & Trauma Surg, Cesena, Italy

[12] Pisa Univ Hosp, Gen Emergency & Trauma Surg, Pisa, Italy

[13] Hosp Univ Pisa AOUP, Dept Surg, Gen & Peritoneal Surg, Pisa, Italy

[14] AOU Modena Univ Modena & Reggio Emilia, Gen & Oncol Surg Unit, Modena, Italy

[15] Ist Nazl Studio & Cura Tumori Fdn Pascale IRCCS, Abdominal Oncol Dept, Colorectal Surg Oncol, Naples, Italy

[16] Fdn IRCCS Policlin San Matteo, Gen Surg, Pavia, Italy

[17] Univ Pisa, Dept Surg Med Mol Pathol & Crit Area, Pisa, Italy

[18] Veneto Inst Oncol IOV IRCCS, Clin Nutr Unit, Padua, Italy

来源：

ESMO OPEN | 2024年 / 9卷 / 04期

关键词：

peritoneal metastases (PM); cytoreductive surgery (CRS); HIPEC; KRAS; colorectal cancer (CRC); HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY; CYTOREDUCTIVE SURGERY; RANDOMIZED-TRIALS; CANCER; BRAF; ASSOCIATION; SURVIVAL; RECURRENCE; THERAPY;

D O I：

10.1016/j.esmoop.2024.102976

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Materials and methods: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. Results: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRAS(MUT1) (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRAS(MUT2) (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRAS(MUT2) mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRAS(MUT1) and KRAS(MUT2) were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRAS(MUT1) showed a similar survival rate to KRAS(WT) patients, whereas KRAS(MUT2) was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). Conclusions: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRAS(MUT1)) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

引用

页数：8

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