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2.
Ann Surg Oncol ; 31(9): 6252-6261, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39003380

RESUMEN

BACKGROUND: The prognostic impact of genetic mutations for patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) of colorectal origin (CRC) is not well defined. OBJECTIVE: We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population. METHODS: A retrospective, bi-institutional study was performed on patients who underwent CRS-HIPEC with targeted mutation data with a median follow-up time of 61 months. Functional link analysis was performed using STRING v11.5. Genes with similar functional significance were clustered using unsupervised k-means clustering. Chi-square, Kaplan-Meier, and the log-rank test were used for comparative statistics. RESULTS: Sixty-four patients with peritoneal carcinomatosis from CRC origin underwent CRS-HIPEC between 2007 and 2022 and genetic mutation data were extracted. We identified 19 unique altered genes, with KRAS (56%), TP53 (33%), and APC (22%) being the most commonly altered; 12.5% had co-altered KRAS/TP53. After creating an interactome map, k-means clustering revealed three functional clusters. Reactome Pathway analysis on three clusters showed unique pathways (1): Ras/FGFR3 signaling; (2) p53 signaling; and (3): NOTCH signaling. Seventy-one percent of patients in cluster 1 had KRAS mutations and a median overall survival of 52.3 months (p < 0.05). CONCLUSIONS: Patients with peritoneal carcinomatosis (PC) of CRC origin who underwent CRS-HIPEC and with tumors that harbored mutations in cluster 1 (Ras/FGFR3 signaling) had worse outcomes. Pathway disruption and a cluster-centric perspective may affect prognosis more than individual genetic alterations in patients with PC of CRC origin.


Asunto(s)
Neoplasias Colorrectales , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Mutación , Neoplasias Peritoneales , Proteínas Proto-Oncogénicas p21(ras) , Proteína p53 Supresora de Tumor , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Femenino , Masculino , Estudios Retrospectivos , Proteínas Proto-Oncogénicas p21(ras)/genética , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/genética , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/genética , Pronóstico , Tasa de Supervivencia , Terapia Combinada , Estudios de Seguimiento , Anciano , Biomarcadores de Tumor/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto
3.
Ann Surg Oncol ; 31(4): 2668-2678, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38127214

RESUMEN

BACKGROUND: Frailty, a multidimensional state leading to reduced physiologic reserve, is associated with worse postoperative outcomes. Despite the availability of various frailty tools, surgeons often make subjective assessments of patients' ability to tolerate surgery. The Risk Analysis Index (RAI) is a validated preoperative frailty assessment tool that has not been studied in cancer patients with plans for curative-intent surgery. METHODS: In this prospective, surgeon-blinded study, patients who had abdominal malignancy with plans for resection underwent preoperative frailty assessment with the RAI and nutrition assessment by measurement of albumin, prealbumin, and C-reactive protein (CRP). Postoperative outcomes and survival were assessed. RESULTS: The study included 220 patients, 158 (72%) of whom were considered frail (RAI ≥21). Frail patients were more likely to be readmitted within 30 and 90 days, (16% vs. 3% [P = 0.006] and 16% vs. 5% [P = 0.025], respectively). Patients with abnormal CRP, prealbumin, and albumin experienced higher rates of unplanned intensive care unit admission (CRP [27% vs. 8%; P < 0.001], albumin [30% vs. 10%; P < 0.001], prealbumin [29% vs. 9%; P < 0.001]) and increased postoperative mortality at 90 and 180 days. Survival was similar for frail and non-frail patients. In the multivariate analysis, frailty remained an independent risk factor for readmission (hazard ratio, 5.58; 95% confidence interval, 1.39-22.15; P = 0.015). In the post hoc analysis using the pre-cancer RAI score, the postoperative outcomes did not differ between the frail and non-frail patients. CONCLUSION: In conjunction with preoperative markers of nutrition, the RAI may be used to identify patients who may benefit from additional preoperative risk stratification and increased postoperative follow-up evaluation.


Asunto(s)
Fragilidad , Desnutrición , Neoplasias , Humanos , Anciano , Fragilidad/complicaciones , Prealbúmina , Estudios Prospectivos , Anciano Frágil , Medición de Riesgo/métodos , Factores de Riesgo , Neoplasias/cirugía , Neoplasias/complicaciones , Desnutrición/etiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos
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