The failing malignant liver

Smith, Belinda; James, Oliver

doi:10.1136/gut.42.4.454

Cited by 12 publications

(4 citation statements)

References 13 publications

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“…Secondary organ failure is a major cause of death in cancer patients and is linked to systemic tumor‐derived factors and to tissue injury upon surgery, chemotherapy, or radiotherapy. Acute liver failure is a common condition in patients at advanced stages of cancer and can develop in the absence of malignant invasion of the liver (Smith & James, 1998), suggesting the involvement of distant signaling via cytokines and EVPs. Hepatic failure can develop following microemboli, which can be directly induced by tumor‐derived EVPs (Gomes et al , 2017; Leal et al , 2017), or might be induced by the infiltration of immune cells in the liver in response to EVP inflammatory and chemoattractant mediators, such as DAMPs (Hoshino et al , 2020; Wu et al , 2010).…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles and particles impact the systemic landscape of cancer

et al. 2022

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Intercellular cross talk between cancer cells and stromal and immune cells is essential for tumor progression and metastasis. Extracellular vesicles and particles (EVPs) are a heterogeneous class of secreted messengers that carry bioactive molecules and that have been shown to be crucial for this cell-cell communication. Here, we highlight the multifaceted roles of EVPs in cancer. Functionally, transfer of EVP cargo between cells influences tumor cell growth and invasion, alters immune cell composition and function, and contributes to stromal cell activation. These EVP-mediated changes impact local tumor progression, foster cultivation of pre-metastatic niches at distant organspecific sites, and mediate systemic effects of cancer. Furthermore, we discuss how exploiting the highly selective enrichment of molecules within EVPs has profound implications for advancing diagnostic and prognostic biomarker development and for improving therapy delivery in cancer patients. Altogether, these investigations into the role of EVPs in cancer have led to discoveries that hold great promise for improving cancer patient care and outcome.

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Section: Introductionmentioning

confidence: 99%

Extracellular vesicles and particles impact the systemic landscape of cancer

et al. 2022

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“…One possible rationale for primary site treatment has been the eradication of subclones with metastatic potential [20], thereby leading to reduced systemic burden of disease. While this mechanism may play a role in patients with M1 ICC, the more intriguing rationale for local therapy for M1 ICC is the mitigation of TRLF, which has been well described in several antecedent studies of locoregional ICC [5, 7, 16, 21]. Our results reaffirm the importance of LC of the primary and/or dominant liver lesion(s) with L-RT as a conduit to both deferring and decreasing rates of local progression, TRLF, and death.…”

Section: Discussionmentioning

confidence: 99%

Definitive Liver Radiotherapy for Intrahepatic Cholangiocarcinoma with Extrahepatic Metastases

Upadhyay

Liao

et al. 2023

Liver Cancer

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Introduction: Tumor-related liver failure (TRLF) is the most common cause of death in patients with intrahepatic cholangiocarcinoma (ICC). Though we previously showed that liver radiotherapy (L-RT) for locally advanced ICC is associated with less frequent TRLF and longer overall survival (OS), the role of L-RT for patients with extrahepatic metastatic disease (M1) remains undefined. We sought to compare outcomes for M1 ICC patients treated with and without L-RT. Methods: We reviewed ICC patients found to have M1 disease at initial diagnosis at a single institution between 2010 and 2021 who received L-RT, matching them with an institutional cohort by propensity score and a National Cancer Database (NCDB) cohort by frequency technique. The median biologically effective dose (BED10) was 98 Gy (interquartile range [IQR] 80.5-97.9 Gy) for L-RT. Patients treated with other local therapies or supportive care alone were excluded. We analyzed survival with Cox proportional hazards modeling. Results: We identified 61 patients who received L-RT and 220 who received chemotherapy alone. At median follow up of 11 months after diagnosis, median OS was 9 months (95% confidence interval [CI] 8-11) and 21 months (CI 17-26) for patients receiving chemotherapy alone and L-RT, respectively. TRLF was the cause of death more often in the patients who received chemotherapy alone compared to those who received L-RT (82% vs. 47%; P=0.001). On multivariable propensity-score matched analysis, associations with lower risk of death included duration of upfront chemotherapy (hazard ratio [HR] 0.82; P=0.005) and receipt of L-RT (HR 0.40; P=0.002). The median OS from diagnosis for NCDB chemotherapy alone cohort was shorter than that of the institutional L-RT cohort (9 vs. 22 months; P<0.001). Discussion/Conclusion: For M1 ICC, L-RT associated with a lower rate of death due to TRLF and longer OS vs. those treated with chemotherapy alone. Prospective studies of L-RT in this setting are warranted.

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“…19,20 Although the elimination of limited subclones with metastatic potential within the primary tumor is itself an intriguing rationale for local therapy, 21 the lethality of malignant hepatic failure adds further justification for liver-directed therapy for hepatobiliary malignant neoplasms. 22,23 The high rate of dissemination and relapse seen in biliary malignant neoplasms has established systemic cytotoxic chemotherapy as the standard of care. 24 While the propriety of primarydirected therapy in a cohort typified by median overall survival of only 1 year may prompt skepticism, continued improvements in operative and radiotherapeutic management may help to facilitate the integration of primary-directed therapy into the metastatic treatment paradigm by enhancing convenience, cost, and toxicity profile.…”

Section: Discussionmentioning

confidence: 99%

“…For oligometastatic colon cancer, aggressive treatment of the metastatic and primary tumor is the standard of care . Although the elimination of limited subclones with metastatic potential within the primary tumor is itself an intriguing rationale for local therapy, the lethality of malignant hepatic failure adds further justification for liver-directed therapy for hepatobiliary malignant neoplasms …”

Section: Discussionmentioning

confidence: 99%

Association of Liver-Directed Local Therapy With Overall Survival in Adults With Metastatic Intrahepatic Cholangiocarcinoma

et al. 2019

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Key PointsQuestionIs the addition of liver-directed local therapy to chemotherapy associated with an improvement to overall survival for patients with metastatic intrahepatic cholangiocarcinoma?FindingsThis cohort study, using data from 2201 patients with metastatic intrahepatic cholangiocarcinoma from the National Cancer Database, found statistically significant higher overall survival in patients treated with chemotherapy and liver-directed surgery or irradiation vs patients treated with chemotherapy alone.MeaningThe findings suggest that patients with metastatic intrahepatic cholangiocarcinoma who receive chemotherapy, definitive treatment to the primary liver tumor in the form of surgery or radiation is associated with improved overall survival.

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The failing malignant liver

Cited by 12 publications

References 13 publications

Extracellular vesicles and particles impact the systemic landscape of cancer

Extracellular vesicles and particles impact the systemic landscape of cancer

Definitive Liver Radiotherapy for Intrahepatic Cholangiocarcinoma with Extrahepatic Metastases

Association of Liver-Directed Local Therapy With Overall Survival in Adults With Metastatic Intrahepatic Cholangiocarcinoma

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