Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing Selective Internal Radiation Therapy

Fahmueller, Yvonne Nadine; Nagel, Dorothea; Hoffmann, Ralf‐Thorsten; Tatsch, Klaus; Jakobs, Tobias; Stieber, P.; Holdenrieder, Stefan

doi:10.1186/1471-2407-12-5

Cited by 56 publications

(66 citation statements)

References 45 publications

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“…With respect to tumor responses for 90 Y radioembolization as monotherapy, the lowest response rate was reported by Fahmueller et al (disease control rate of 29%) (17), and the highest response rate was reported by Kennedy et al…”

Section: Discussionmentioning

confidence: 91%

“…Without information on sampling interval and follow-up duration, comparison of responses between studies becomes complicated. In addition, number of patients lost to follow-up is important, including a statement on the handling of this parameter (e.g., calculating worst-case scenario by considering patients lost to follow-up as having progressive disease) (17).…”

Section: Discussionmentioning

confidence: 99%

“…Cross-referencing did not yield any additional relevant articles. Among the selected studies reporting on 90 Y radioembolization as monotherapy were 3 phase 2 trials (7,15,16), 2 prospective cohort studies (12,17), and 8 retrospective cohort studies (9,(18)(19)(20)(21)(22)(23)(24), involving a total of 901 patients (Supplemental Table 1). All studies had included patients with unresectable and chemorefractory liver lesions (i.e., salvage patients), and most studies included patients with liver-dominant disease, that is, the studies accepted patients with minor extrahepatic disease for treatment.…”

Section: Study Description and Critical Appraisalmentioning

confidence: 99%

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Radioembolization for Treatment of Salvage Patients with Colorectal Cancer Liver Metastases: A Systematic Review

et al. 2013

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Currently, there is no consensus on the use of 90 Y radioembolization for salvage patients with colorectal cancer liver metastases. The purpose of this study was to provide a comprehensive overview of the available data on tumor response and survival after 90 Y radioembolization for this group of patients. Methods: A systematic literature search was conducted in PubMed (Medline), Excerpta Medica (EMBASE), and the Cochrane Library (September 2012) with synonyms for "radioembolization" and "colorectal cancer liver metastases." Results were described separately for patient cohorts treated with 90 Y radioembolization as monotherapy and with 90 Y radioembolization in combination with chemotherapy. Results: The search yielded 13 relevant articles for systematic review on 90 Y radioembolization as monotherapy and 13 relevant articles on 90 Y radioembolization combined with chemotherapy. Disease control rates (i.e., complete response, partial response, and stable disease) ranged from 29% to 90% for 90 Y radioembolization as monotherapy and from 59% to 100% for 90 Y radioembolization combined with chemotherapy. Heterogeneity in the data prohibited pooling of response rates. Survival proportions at 12 mo ranged from 37% to 59% for 90 Y radioembolization as monotherapy and from 43% to 74% for 90 Y radioembolization combined with chemotherapy. Conclusion: In the studies included in this systematic review, approximately 50% of salvage patients with colorectal cancer liver metastases survive more than 12 mo after treatment with 90 Y radioembolization, either as monotherapy or in combination with chemotherapy. Heterogeneity between studies has unfortunately prohibited pooling of data. Future research will discern the precise role of 90 Y radioembolization in general clinical practice in comparison with chemotherapy.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Study Description and Critical Appraisalmentioning

confidence: 99%

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Radioembolization for Treatment of Salvage Patients with Colorectal Cancer Liver Metastases: A Systematic Review

et al. 2013

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“…Im Rahmen der lokalen Therapien wurden 49 Patienten mit Leber-Metastasen eines kolorektalen Karzinoms, die eine Selektive Interne Radio-Therapie (SIRT) erhielten [161,173] , sowie 50 Patienten mit einem prim ä ren Leberzellkarzinom, die mit einer Trans-Arteriellen ChemoEmbolisation (TACE) behandelt wurden, untersucht [162,174] . Grundlage dieser Therapien ist die doppelte Gef ä ß-versorgung der Leber: Gesundes Lebergewebe wird dabei ü berwiegend durch die Portalvene, Tumorgewebe durch die Leberarterie versorgt.…”

Section: Immunogene Zelltodmarker In Der Beurteilung Des Therapieanspunclassified

“…In ä hnlicher Weise waren hohe Basis-und 24 h-Werte von HMGB1 au ß erdem mit einem ung ü nstigen Langzeit ü berleben assoziiert. In der multivariaten Analyse mit Tumor-, Leber-und Inflammationsmarkern wurden HMGB1 und CRP als unabh ä ngige prognostische Parameter best ä tigt [161,173] .…”

Section: Immunogene Zelltodmarker In Der Beurteilung Des Therapieanspunclassified

Immunogene Zelltodmarker HMGB1 und sRAGE als neue prädiktive und prognostische Serum Biomarker bei Tumorerkrankungen/Immunogenic cell death markers HMGB1 and sRAGE as new predictive and prognostic serum biomarkers in cancer disease

Wittwer¹,

Holdenrieder²

2013

Laboratoriumsmedizin

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ZusammenfassungImmunogene Zelltodmarker sind eine inhomogene Gruppe von Molekülen, die während Zelltodprozessen wie Apoptose, Nekrose oder weiteren Formen freigesetzt werden. Je nach Zusammensetzung des extrazellulären Milieus können diese „Danger associated molecular patterns“ (DAMPs) wie das „High mobility group box 1“ (HMGB1) Protein das Immunsystem stimulierend oder inhibierend beeinflussen. Bei Tumorerkrankungen scheint eine kontinuierliche Freisetzung von HMGB1, u.a. über eine Vermittlung durch den zellulären Bindungspartner „Receptor of advanced glycation end products“ (RAGE), zu einer Förderung des Tumorwachstums zu führen, während die pulsatile Freisetzung während zytotoxischer Therapie zu einer verbesserten antitumorösen Immunantwort beitragen könnte. Lösliches RAGE (sRAGE) kann hingegen die Effekte von extrazellulärem HMGB1 abpuffern. In diesem Review werden die strukturellen und funktionalen Charakteristika dieser immunogenen Zelltodmarker sowie ihre Rolle in der Pathophysiologie von nicht-malignen und malignen Erkrankungen vorgestellt; sodann wird ihre Relevanz als Serum-Biomarker für die Diagnose, die Prognoseabschätzung, die Prädiktion und das Monitoring des Ansprechens einer zytotoxischen Therapie bei Tumorpatienten beleuchtet. Bei Patienten mit verschiedenen Tumorerkrankungen wurden im Vergleich zu gesunden Personen erhöhte Serumkonzentrationen von HMGB1 und niedrigere sRAGE-Werte gefunden. Zudem waren hohe HMGB1- und niedrige sRAGE-Serumwerte vor und während einer zytotoxischen Therapie mit einem unzureichenden Ansprechen auf die Behandlung und einem kürzeren Überleben assoziiert. Diese Ergebnisse weisen die immunogenen Zelltodmarker HMGB1 und sRAGE als neue, vielversprechende Biomarker zur Abschätzung der Prognose, Stratifikation der Patienten und zum Therapiemonitoring bei Tumorpatienten aus.

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Immunogenic cell death biomarkers HMGB1, RAGE, and DNAse indicate response to radioembolization therapy and prognosis in colorectal cancer patients

Fahmueller¹,

Nagel²,

Hoffmann

et al. 2013

Intl Journal of Cancer

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Radioembolization therapy (RE) is an efficient locoregional treatment for liver metastases from colorectal cancer. Serum biomarkers involved in immunogenic cell death are potentially valuable for early predicting therapy response and estimating prognosis. In a prospective observation study, blood samples were taken from 49 consecutive colorectal cancer patients with extensive hepatic metastases before, 24 and 48 hr after RE. Serum levels of high mobility group box 1 (HMGB1), receptor of glycation end products (RAGE) and activity of desoxyribonuclease were compared with response to therapy regularly determined radiologically 3 months after therapy and with overall survival. Serum levels of HMGB1 were increased already 24 hr after RE, while RAGE levels were decreased and DNAse remained unchanged. In radiological staging, 35 patients demonstrated disease progression while 14 patients had stable disease or remission. Serum HMGB1 levels 24 hr after RE were significantly higher in progressive than in nonprogressive patients while for RAGE and DNAse no difference was observed between the response groups. Concerning overall survival, high pretherapeutic (0 hr) and 24 hr levels of HMGB1 were associated with poor outcome. Multivariate analysis including HMGB1, tumor, liver and inflammation markers revealed HMGB1 and CRP as independent prognostic parameters. HMGB1 is a valuable serum biomarker for early estimation of therapy response and prognosis in colorectal cancer patients with liver metastases undergoing RE therapy.Liver metastases are detected in 15-20% of colorectal cancer patients-the third most common cancer worldwide-at time of first diagnosis and in another 15-20% during the further course of disease.1,2 Presence of metastases is associated with a poor 5-year survival rate of 12%.3 Curative surgical resection of hepatic metastases is only possible in less than 25% of colorectal cancer patients. 4 For other patients, new local therapies like radiofrequency ablation (RFA), cryotherapy, and microwave ablation are promising approaches. However, local diameter of liver lesions considerably influences recurrence rates. In particular, lesion sizes of more than 4 cm are associated with worse outcome.5 While RFA and cryotherapy cannot be performed if disseminated liver metastases are present, radioembolization therapy (RE) is a potentially valuable alternative to systemic chemotherapy in those cases. 6 As liver metastases tend to obtain their blood supply from the hepatic artery rather than from the portal vein, microspheres loaded with Yttrium 90 administered through the hepatic artery directly damage the tumor and relatively spare the radiation sensible liver tissue. 7,8 Thereby an average tumor dosage of 200-300 Gy is applied 9 to the tumor which is almost the tenfold dose as it would be possible with external beam radiation.

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Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing Selective Internal Radiation Therapy

Cited by 56 publications

References 45 publications

Radioembolization for Treatment of Salvage Patients with Colorectal Cancer Liver Metastases: A Systematic Review

Radioembolization for Treatment of Salvage Patients with Colorectal Cancer Liver Metastases: A Systematic Review

Immunogene Zelltodmarker HMGB1 und sRAGE als neue prädiktive und prognostische Serum Biomarker bei Tumorerkrankungen/Immunogenic cell death markers HMGB1 and sRAGE as new predictive and prognostic serum biomarkers in cancer disease

Immunogenic cell death biomarkers HMGB1, RAGE, and DNAse indicate response to radioembolization therapy and prognosis in colorectal cancer patients

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