Prognostic Impact and Utility of Immunoprofiling in the Selection of Patients with Colorectal Peritoneal Carcinomatosis for Cytoreductive Surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC)

Garland-Kledzik, Mary; Uppal, Abhineet; Naeini, Yalda; Stern, Stacey; Erali, Richard A.; Scholer, Anthony; Khader, Adam; Santamaria-Barria, Juan A.; Cummins-Perry, Kathleen; Zhou, Yi; Votanopoulos, Konstantinos I.; Shen, Perry; Levine, Edward A.; Bilchik, Anton J.

doi:10.1007/s11605-020-04886-y

Cited by 8 publications

(9 citation statements)

References 26 publications

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“…Although further research should clarify the role of the immune system in the development and eradication of peritoneal metastases, some studies indicated the importance of the presence of specific immune cells in the peritoneum. For example, the ratio of tumor infiltrating CD4+ T cells has been associated with improved survival of peritoneal metastasis patients with low tumor load 54 . Other subgroup-specific vulnerabilities might also offer directions towards more personalized therapies, or to development of predictive markers to support early detection.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of colorectal cancer related peritoneal metastatic disease

et al. 2022

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A significant proportion of colorectal cancer (CRC) patients develop peritoneal metastases (PM) in the course of their disease. PMs are associated with a poor quality of life, significant morbidity and dismal disease outcome. To improve care for this patient group, a better understanding of the molecular characteristics of CRC-PM is required. Here we present a comprehensive molecular characterization of a cohort of 52 patients. This reveals that CRC-PM represent a distinct CRC molecular subtype, CMS4, but can be further divided in three separate categories, each presenting with unique features. We uncover that the CMS4-associated structural protein Moesin plays a key role in peritoneal dissemination. Finally, we define specific evolutionary features of CRC-PM which indicate that polyclonal metastatic seeding underlies these lesions. Together our results suggest that CRC-PM should be perceived as a distinct disease entity.

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Section: Discussionmentioning

confidence: 99%

Molecular characterization of colorectal cancer related peritoneal metastatic disease

et al. 2022

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“…However, a recent study among colorectal PM patients with a low PCI score showed an increased survival in patients with a low CD3+/CD4+ ratio. 81 In this study, the Immunoscore was not of prognostic significance, possibly because the role of the immune system within the peritoneal cavity is less significant. Nevertheless, immune profiling in colorectal PM warrants further investigation to assess the prognostic value in both systemic and surgical therapy.…”

Section: Immunoprofilingmentioning

confidence: 56%

Effective Strategies to Predict Survival of Colorectal Peritoneal Metastases Patients Eligible for Cytoreductive Surgery and HIPEC

Simkens¹,

Wintjens²,

Rovers

et al. 2021

CMAR

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Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), often combined with systemic therapy, can be offered to selected colorectal peritoneal metastases (PM) patients. However, clinical heterogeneity and the lack of high-level evidence challenges determination of the correct treatment strategy. This review aims to provide an overview of current strategies to predict survival of colorectal PM patients treated with CRS and HIPEC, guiding clinicians to select a suitable treatment-strategy and to inform patients about their prognosis. First, the prognostic relevance of several clinicopathological prognostic factors, such as extent of PM, location of primary tumor, histology type, and the presence of lymph node or liver metastases will be discussed. Subsequently, special attention will be given to recent developments in several aspects of tumor biology such as RAF/RAS mutations, circulating tumor DNA, immunoprofiling, and consensus molecular subtypes. Finally, currently available prognostic models to predict survival will be evaluated, concluding these models perform moderate to good, but most of them partly rely on intra-operative data. New insights in tumor biology, as well as the reliable assessment of extent of peritoneal disease by diffusion weighted MRI pose promising opportunities to establish an adequate and clinically meaningful preoperative prognostic model in the near future.

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“…[27][28][29][30][31][32][33][34][35] The number of reports on image analysis using ImageJ has been increasing, as it is used in diverse fields. 36,37 Conventional image analysis is qualitative and prone to variation, but ImageJ images can be quantified and captured objectively. In the present study, we used a digital analysis to semiautomatically and objectively evaluate TSR and ISH.…”

Section: Discussionmentioning

confidence: 99%

Value of the Tumor-Stroma Ratio and Structural Heterogeneity Measured by a Novel Semiautomatic Image Analysis Technique for Predicting Survival in Patients With Colon Cancer

Inoue

Kudou

Shiozaki

et al. 2022

Diseases of the Colon &Amp; Rectum

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BACKGROUND: The tumor-stroma ratio and intratumor stromal heterogeneity have been identified as prognostic factors for several carcinomas. Recent advancements in image analysis technologies and their application to medicine have enabled detailed analysis of clinical data beyond human cognition. OBJECTIVE: This study aimed to investigate the tumor-stroma ratio and intratumor stromal heterogeneity measured using a novel objective and semiautomatic method with image analysis. DESIGN: A retrospective cohort design. SETTINGS: Single institution. PATIENTS: This study included patients who underwent curative colectomy for colon cancer. MAIN OUTCOME MEASURES: The survival analyses between tumor-stroma ratio or intratumor stromal heterogeneity high and low groups after colectomy were assessed in multivariate analyses. RESULTS: Two hundred patients were divided into 2 groups based on the median tumor-stroma ratio and intratumor stromal heterogeneity values. The 5-year overall survival and relapse-free survival rates after colectomy significantly differed between the high and low tumor-stroma ratio or intratumor stromal heterogeneity groups. Multivariate analysis identified low tumor-stroma ratio (HR: 1.90, p = 0.03) and high intratumor stromal heterogeneity (HR: 2.44, p = 0.002) as independent poor prognostic factors for relapse-free survival. The tumor-stroma ratio and intratumor stromal heterogeneity correlated with the duration from curative surgery to recurrence. Furthermore, postoperative recurrence within 2 years was predicted with higher accuracy by using the tumor-stroma ratio or intratumor stromal heterogeneity than by using the pathological stage. In a validation cohort, interobserver agreement was assessed by 2 observers, and Cohen’s κ coefficient for the tumor-stroma ratio (κ value: 0.70) and intratumor stromal heterogeneity (κ value: 0.60) revealed a substantial interobserver agreement. LIMITATIONS: This study was limited by its retrospective, single-institution design. CONCLUSIONS: Tumor-stroma ratio and intratumor stromal heterogeneity calculated using image analysis software have potential as imaging biomarkers for predicting the survival of patients with colon cancer after colectomy. See Video Abstract at http://links.lww.com/DCR/C114. VALOR DE LA PROPORCIÓN DE ESTROMA TUMORAL Y LA HETEROGENEIDAD ESTRUCTURAL MEDIDOS POR UNA NUEVA TÉCNICA DE ANÁLISIS DE IMÁGENES SEMIAUTOMÁTICA PARA PREDECIR LA SUPERVIVENCIA EN PACIENTES CON CÁNCER DE COLON ANTECEDENTES: La proporción de estroma tumoral y la heterogeneidad del estroma intratumoral han sido identificados como factores pronósticos para varios tipos de carcinomas. Los avances recientes en cuanto a las tecnologías de análisis de imágenes y sus aplicaciones en la medicina, han permitido un análisis detallado de los datos clínicos más allá del conocimiento humano. OBJETIVO: Investigar la relación del estroma tumoral y la heterogeneidad del estroma intratumoral calculados mediante un nuevo método objetivo y semiautomático para el análisis de imágenes. DISEÑO: Diseño de cohorte retrospectivo. AJUSTES: Institución única. PACIENTES: Pacientes sometidos a colectomía curativa por cáncer de colon. PRINCIPALES MEDIDAS DE RESULTADO: Los análisis de supervivencia entre la relación del estroma tumoral o la heterogeneidad del estroma intratumoral entre los grupos con valores altos y bajos tras la colectomía, fueron evaluados en análisis multivariados. RESULTADOS: Fueron divididos 200 pacientes en dos grupos basados en la mediana de la proporción con respecto a los valores del estroma tumoral y la heterogeneidad del estroma intratumoral. Las tasas de supervivencia general a los 5 años y de supervivencia libre de recaídas después de la colectomía, difirieron significativamente entre los grupos con índice de estroma tumoral o heterogeneidad del estroma intratumoral altos y bajos. El análisis multivariante identificó una proporción de estroma tumoral baja (cociente de riesgos instantáneos: 1.90, p = 0.03) y una heterogeneidad estromal intratumoral alta (cociente de riesgos instantáneos: 2.44, p = 0.002) como factores independientes de mal pronóstico para la supervivencia libre de recaídas. La proporción de estroma tumoral y la heterogeneidad del estroma intratumoral se correlacionaron con la duración de la recurrencia desde la cirugía. Además, la recurrencia posoperatoria dentro de los 2 años se predijo con mayor precisión mediante el uso del índice de estroma tumoral o la heterogeneidad del estroma intratumoral que mediante el uso del estadio patológico. En una cohorte de validación, la concordancia interobservador fue evaluada por dos observadores, y el coeficiente Kappa de Cohen para la proporción de estroma tumoral y la heterogeneidad estromal intratumoral reveló una concordancia interobservador sustancial (valor Kappa: 0.70, 0.60, respectivamente). LIMITACIONES: Este estudio estuvo limitado por su diseño retrospectivo de una sola institución. CONCLUSIONES: La proporción del estroma tumoral y la heterogeneidad del estroma intratumoral calculadas mediante software de análisis de imágenes tienen potencial como biomarcadores de imagen para predecir la supervivencia de los pacientes con cáncer de colon tras la colectomía. Consulte Video Resumen en http://links.lww.com/DCR/C114. (Traducción—Dr. Osvaldo Gauto)

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Prognostic Impact and Utility of Immunoprofiling in the Selection of Patients with Colorectal Peritoneal Carcinomatosis for Cytoreductive Surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC)

Cited by 8 publications

References 26 publications

Molecular characterization of colorectal cancer related peritoneal metastatic disease

Molecular characterization of colorectal cancer related peritoneal metastatic disease

Effective Strategies to Predict Survival of Colorectal Peritoneal Metastases Patients Eligible for Cytoreductive Surgery and HIPEC

Value of the Tumor-Stroma Ratio and Structural Heterogeneity Measured by a Novel Semiautomatic Image Analysis Technique for Predicting Survival in Patients With Colon Cancer

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