Clinical significance of disseminated tumour cells in non-small cell lung cancer

Rud, Ane Kongsgaard; Borgen, Elin; Mælandsmo, Gunhild Mari; Flatmark, Kjersti; Le, H. Q.; Josefsen, Dag; Solvoll, I; Schirmer, Cecilie Bendigtsen; Helland, Åslaug; Lh, Jørgensen; Brustugun, Odd Terje; Fodstad, Øystein; Boye, Kjetil

doi:10.1038/bjc.2013.450

Cited by 18 publications

(19 citation statements)

References 38 publications

(65 reference statements)

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“…infusion. The presence of micrometastatic cells has been shown to have a prognostic value in patients with metastatic disease ( Leong and Tseng, 2014 ), and EpCAM is a commonly used antigen for detection of circulating tumour cells ( Flatmark et al , 2011 ; Tveito et al , 2011 ; Rud et al , 2013 ). This potential surrogate marker might be used to evaluate treatment response to anti-EpCAM targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

Phase I trial of EpCAM-targeting immunotoxin MOC31PE, alone and in combination with cyclosporin

et al. 2015

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Background:A phase I trial was performed to determine the maximum tolerated dose (MTD), safety, pharmacokinetics and immunogenicity of the anti-EpCAM immunotoxin (IT) MOC31PE in cancer patients. An important part of the study was to investigate whether the addition of Sandimmune (cyclosporin, CsA) suppressed the development of anti-IT antibodies.Methods:Patients with EpCAM-positive metastatic disease were eligible for treatment with intravenous MOC31PE using a modified Fibonacci dose escalation sequence. Maximum tolerated dose was first established without, then with intravenously administered CsA.Results:Sixty-three patients were treated with MOC31PE in doses ranging from 0.5 to 8 μg kg−1. Maximum tolerated dose was 8 μg kg−1 for MOC31PE alone, and 6.5 μg kg−1 when combined with CsA. The dose-limiting adverse event was reversible liver toxicity. No radiological complete or partial responses were observed, whereas stable disease was seen in 36% of the patients receiving MOC31PE only. The pharmacokinetic profile of MOC31PE was characterised by linear kinetics and with a half-life of ∼3 h. The addition of CsA delayed the generation of anti-IT antibodies.Conclusions:Intravenous infusion of MOC31PE can safely be administered to cancer patients. Immune suppression with CsA delays the development of anti-MOC31PE antibodies. The antitumour effect of MOC31PE warrants further evaluation in EpCAM-positive metastatic disease.

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Section: Discussionmentioning

confidence: 99%

Phase I trial of EpCAM-targeting immunotoxin MOC31PE, alone and in combination with cyclosporin

et al. 2015

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“…59 However, the largest study conducted so far on 296 patients could not find a significant association between DTCs and clinical outcome. 62 Using RT-PCR-based assays, the follow-up database is small thus far. Analyzing a small cohort of 50 patients free of overt distant metastases, the presence of MAGE-A was associated with poor prognosis.…”

Section: Clinical Relevance Of Dtcs In Lung Cancermentioning

confidence: 99%

Bone marrow as a reservoir for disseminated tumor cells: a special source for liquid biopsy in cancer patients

Pantel¹,

Alix‐Panabières²

2014

BoneKEy Reports

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Besides circulating tumor cells, disseminated tumor cells (DTCs) in bone marrow (BM) might be used as a 'liquid biopsy' to obtain information helpful to steer therapies in individual patients. Moreover, the molecular characterization of DTCs may provide important insight into the biology of cancer metastasis. BM is a frequent site of metastasis in breast, prostate and lung cancer, and it might represent a sanctuary site for DTCs derived from various additional types of epithelial tumors. Highly sensitive and specific immunocytological and molecular methods enable the detection of DTCs in BM of cancer patients at the single-cell level years before the occurrence of metastases. This information might be useful to assess individual prognosis and stratify patients at risk to systemic adjuvant anti-cancer therapies. Although most data on the prognostic value of DTCs are available for breast cancer, several single institution studies including patients with colon, lung, prostate, esophageal, gastric, pancreatic, ovarian and head and neck carcinomas have also documented an association between the presence of DTCs at primary surgery and subsequent metastatic relapse. Most DTCs are in a dormant (that is, non-proliferative) stage, frequently express HER2 and display a cancer stem cell and immune escape phenotype. Here, we summarize the current knowledge about specific biological properties of DTCs in BM, and discuss the clinical relevance of DTC detection in cancer patients with regard to an improved individualized therapeutic management. This will stimulate further technical developments that may make BM sampling more acceptable for the clinical management of patients with solid tumors.

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“…The methods used for detection have traditionally been immunohistochemistry (IHC) with antibodies targeting epithelial-specific proteins like cytokeratins [ 6 – 18 ], and molecular methods using RT-PCR for detection of tumor- or epithelial cell specific mRNA transcripts [ 3 , 19 – 25 ]. Our group has previously published a study where we investigated the presence of DTCs in bone marrow aspirates from patients undergoing lung cancer surgery by the use of immunomagnetic selection (IMS) [ 26 ]. In the present study we have used IMS to investigate the presence of DTCs in lymph node tissue prospectively collected from patients with early stage NSCLC undergoing curatively intended surgery.…”

Section: Introductionmentioning

confidence: 99%

Detection of disseminated tumor cells in lymph nodes from patients with early stage non-small cell lung cancer

et al. 2016

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BackgroundThe regional lymph node involvement is a major prognostic factor in patients with non-small cell lung cancer (NSCLC) undergoing surgical resection. Disease relapse is common, suggesting that early disseminated disease is already present in the regional lymph nodes at the time of surgery, and that the current nodal staging classification might be suboptimal. Early detection of disseminated tumor cells (DTCs) in lymph nodes could potentially enable identification of subcategories of patients with high risk of disease relapse.MethodLymph node samples were collected from 128 NSCLC patients at the time of surgery and the presence of DTCs determined by immunomagnetic selection (IMS) using the MOC31 antibody recognizing EpCAM. Results obtained with IMS were compared to the pathological staging obtained by histopathology. Associations between the presence of DTCs and clinicopathological variables and patient outcome were investigated.ResultsDTCs were detected in 40 % of the lymph node samples by IMS. Their presence was significantly associated with pN status as assessed by histopathology, and samples from 83 % of the patients with lymph node metastases (pN1-2) had detectable DTCs. In the group of patients who were negative for lymph node metastases by standard histopathology (pN0) DTCs were detected in 32 %. The presence of DTCs was not associated with any other clinicopathological variables. Patients with IMS-positive samples showed decreased relapse free survival compared to patients with IMS-negative samples, but the difference was not statistically significant. The pN status was significantly associated with both relapse free and overall survival, but the presence of DTCs had no prognostic impact in the subcategory of patients with pN0 status.ConclusionOur findings do not support further development of lymph node DTC detection for clinical use in early stage NSCLC.

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Clinical significance of disseminated tumour cells in non-small cell lung cancer

Cited by 18 publications

References 38 publications

Phase I trial of EpCAM-targeting immunotoxin MOC31PE, alone and in combination with cyclosporin

Phase I trial of EpCAM-targeting immunotoxin MOC31PE, alone and in combination with cyclosporin

Bone marrow as a reservoir for disseminated tumor cells: a special source for liquid biopsy in cancer patients

Detection of disseminated tumor cells in lymph nodes from patients with early stage non-small cell lung cancer

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