Multicentre evaluation of intraoperative molecular analysis of sentinel lymph nodes in breast carcinoma

Snook, Kylie; Layer, G. T.; Jackson, Peter A.; Vries, Corinne S de; Shousha, S; Sinnett, H. D.; Nigar, E.; Singhal, Hemant; Chia, Yoon; Cunnick, Giles; Kissin, Mark

doi:10.1002/bjs.7347

Cited by 94 publications

(74 citation statements)

References 35 publications

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“…19 However, samples from the same node used partly for molecular analysis and partly for morphological analysis generate obvious discrepancies because of uneven tissue distribution. 20 , 21 For example in a previous study, using a fixation procedure that preserved both morphology and high-quality mRNA, we demonstrated, for example, that when metastases >2 mm were located at a pole of a lymph node they might be missed by either hematoxylin & eosin (H&E), immunostaining or RT-PCR applied to samples obtained from the opposite pole of the same lymph node. 21 This data is in line with a previous geometrical model, which showed that incomplete sectioning of the SLNs in extreme situations would almost completely miss metastases >2 mm which would be identified at best as ITC.…”

Section: Reliability Of Whole Sentinel Lymph Node Analysis By Onestepmentioning

confidence: 94%

“…21 The tissue allocation bias has been regarded as one of the main causes of discordance when comparing the 2 procedures. 20 , 21 However, it has never been discussed whether the micrometastases detected on a sample by molecular assay should be added, for example, to the micrometastases diagnosed by standard histology on the parallel sample of the same SLN to obtain a final evaluation of the tumor burden. These variables may impact heavily on nodal staging of the SLN, because variations in the dimension of the metastasis in the range of microns or a tenth of cells may move a patient from the pN0 (absence of metastases) to the pN1 (presence of metastases) stage and vice versa.…”

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confidence: 99%

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Reliability of Whole Sentinel Lymph Node Analysis by One-Step Nucleic Acid Amplification for Intraoperative Diagnosis of Breast Cancer Metastases

et al. 2012

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Objective: To assess the reliability of using the One-Step Nucleic Acid Amplification (OSNA) assay as a single test on whole sentinel lymph nodes (SLN) as a method of intraoperative diagnosis and staging of SLNs in breast cancer.Background: Combining histological and molecular assessment of metastasis on the same SLN may not fully reproduce the actual load of cancer cells present in the SLN and create problems in decisions regarding axillary dissection.

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Section: Reliability Of Whole Sentinel Lymph Node Analysis By Onestepmentioning

confidence: 94%

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confidence: 99%

Reliability of Whole Sentinel Lymph Node Analysis by One-Step Nucleic Acid Amplification for Intraoperative Diagnosis of Breast Cancer Metastases

et al. 2012

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“…Sixteen test accuracy papers were included for OSNA, [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] with two papers reporting the same study. Two unpublished papers 40,66 for Metasin were identified and assessed using the Standards for the Reporting of Diagnostic Accuracy Studies (STARD) in Table 7.…”

Section: Number and Description Of Included Studiesmentioning

confidence: 99%

“…Snook et al 61 reported on a UK single-gate, prospective, multicentre evaluation of OSNA involving four centres. In total, 204 patients were recruited, providing 395 SLNs, although there are no further details on recruitment.…”

Section: Assessment Of Clinical Effectivenessmentioning

confidence: 99%

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A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer

Huxley

Jones-Hughes

Snowsill

et al. 2015

Health Technology Assessment

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BackgroundIn breast cancer patients, sentinel lymph node biopsy is carried out at the same time as the removal of the primary tumour to postoperatively test with histopathology for regional metastases in the sentinel lymph node. Those patients with positive test results are then operated on 2–4 weeks after primary surgery to remove the lymph nodes from the axilla (axillary lymph node dissection, ALND). New molecular tests RD-100i [one-step nucleic acid amplification (OSNA); based on messenger RNA amplification to identify the cytokeratin-19 (CK19) gene marker] (Sysmex, Norderstedt, Germany) and Metasin (using theCK19and mammaglobin gene markers) (Cellular Pathology, Princess Alexandra Hospital NHS Trust, Harlow, UK) are intended to provide an intraoperative diagnosis, thereby avoiding the need for postoperative histopathology and, in positive cases, a second operation for ALND.ObjectiveTo evaluate the clinical effectiveness and cost-effectiveness of using OSNA and Metasin in the NHS in England for the intraoperative diagnosis of sentinel lymph nodes metastases, compared with postoperative histopathology, the current standard.Data sourcesElectronic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library and the Health Economic Evaluations Database as well as clinical trial registries, grey literature and conference proceedings were searched up to July 2012.Review methodsA systematic review of the evidence was carried out using standard methods. Single-gate studies were used to estimate the accuracy of OSNA with histopathology as the reference standard. The cost-effectiveness analysis adapted an existing simulation model of the long-term costs and health implications of early breast cancer diagnostic outcomes. The model accounted for the costs of an extended first operation with intraoperative testing, the loss of health-related quality of life (disutility) from waiting for postoperative test results, disutility and costs of a second operation, and long-term costs and disutility from lymphoedema related to ALND, adjuvant therapy, locoregional recurrence and metastatic recurrence.ResultsA total of 724 references were identified in the searches, of which 17 studies assessing test accuracy were included in the review, 15 on OSNA and two on Metasin. Both Metasin studies were unpublished. OSNA sensitivity of 84.5% [95% confidence interval (CI) 74.7% to 91.0%] and specificity of 91.8% (95% CI 87.8% to 94.6%) for patient nodal status were estimated in a meta-analysis of five studies [unadjusted for tissue allocation bias (TAB)]. At these values and a 20% node-positive rate, OSNA resulted in lifetime discounted cost-savings of £498 and a quality-adjusted life-year (QALY) loss of 0.048 relative to histopathology, that is, £4324 saved per QALY lost. The most favourable plausible scenario for OSNA in terms of the node-positive rate (range 10–40%), diagnostic accuracy values (91.3% sensitivity and 94.2% specificity, from three reports that adjusted for TAB), the costs of histopathology, OSNA and second surgery, and long-term costs and utilities resulted in a maximum saving per QALY lost of £10,500; OSNA sensitivity and specificity would need to be ≥ 95% for this figure to be ≥ £20,000.LimitationsThere is limited evidence on the diagnostic test accuracy of intraoperative tests. The quality of information on costs of resource utilisation during the diagnostic pathway is low and no evidence exists on the disutility of waiting for a second surgery. No comparative studies exist that report clinical outcomes of intraoperative diagnostic tests. These knowledge gaps have more influence on the decision than current uncertainty in the performance of postoperative histopathology in standard practice.ConclusionsOne-step nucleic acid amplification is not cost-effective for the intraoperative diagnosis of sentinel lymph node metastases. OSNA is less accurate than histopathology and the consequent loss of health benefits in this patient group is not compensated for by health gains elsewhere in the health system that may be obtained with the cost-savings made. The evidence on Metasin is insufficient to evaluate its cost-effectiveness.Study registrationThis study is registered as PROSPERO CRD42012002889.FundingThe National Institute for Health Research Health Technology Assessment programme.

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The advantage of one‐step nucleic acid amplification for the diagnosis of lymph node metastasis in colorectal cancer patients

Hiyoshi

Akiyoshi

Fukunaga

2020

Annals of Gastroent Surgery

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Generally, the postoperative examination of lymph nodes (LNs) is based on a microscopic examination of one hematoxylin and eosin (HE)‐stained slide; however, an examination of only one part of the LN might lead to incorrect staging of the tumor due to tissue allocation bias. Although multilevel sectioning and the use of immunohistochemistry (IHC) have improved the detection of micrometastases in LNs, this approach is laborious, time‐consuming, and costly. A novel molecular technique for the detection of LN metastases of tumors, called one‐step nucleic acid amplification (OSNA), is a rapid and semi‐quantitative examination quantifying the number of cytokeratin 19 (CK‐19) mRNA copies derived from a tumor. OSNA is already in clinical use for the diagnosis of LN metastasis in breast cancer patients; however, the use of OSNA is under investigation with promising results for colorectal cancer (CRC). The present review assessed recent studies on OSNA vs a histopathological examination and its implications for CRC staging and treatment. A total of 16 studies of OSNA in CRC yielded by a PubMed search were reviewed. Among them, seven studies evaluating the diagnostic performance revealed that OSNA had a high specificity (96.8%), high concordance rate (96.0%), and negative predictive value (98.6%) in a pooled assessment. In addition, four studies examining the utility of OSNA in sentinel LNs (SLNs) and two studies focusing on upstaging in pathologically node‐negative CRC patients were also reviewed. Multicenter prospective studies with a large cohort of CRC patients are warranted to reveal the benefits of OSNA in the future.

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Multicentre evaluation of intraoperative molecular analysis of sentinel lymph nodes in breast carcinoma

Abstract: OSNA enables accurate automated intraoperative diagnosis and can be used successfully in different UK hospitals. When the SLN is shown to be positive, the patient can undergo immediate axillary clearance under the same anaesthetic rather than having a delayed second procedure.

Cited by 94 publications

References 35 publications

Reliability of Whole Sentinel Lymph Node Analysis by One-Step Nucleic Acid Amplification for Intraoperative Diagnosis of Breast Cancer Metastases

Reliability of Whole Sentinel Lymph Node Analysis by One-Step Nucleic Acid Amplification for Intraoperative Diagnosis of Breast Cancer Metastases

A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer

The advantage of one‐step nucleic acid amplification for the diagnosis of lymph node metastasis in colorectal cancer patients

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