Cancer Treatment Today » Tests

BREVAgen – pro

M Levin, MD — Fri, 20 Dec 2013 17:02:34 +0000

BREVAGen evaluates 7 breast cancer-associated SNPs identified in genome-wide association studies (GWAS). Risk is calculated by multiplying the product of the individual SNP risks by the Gail model risk. BREVAGen has been evaluated for use in Caucasian women of European descent age 35 years and older. According to the BREVAGen website, “suitable candidates” for testing include women with a Gail lifetime risk of 15% or greater; with high lifetime estrogen exposure (e.g., early menarche and late menopause); or with relatives diagnosed with breast cancer. BREVAGen is not suitable for women with previous diagnoses of lobular carcinoma in situ, ductal carcinoma in situ, or breast cancer, since the Gail model cannot calculate breast cancer risk accurately for such women, or for women with an extensive family history of breast and ovarian cancer.

BREVAgen was validated only in comparison to Gail score. Being that the Gail score is the least sensitive scoring tool available and that it is widely considered inadequate, it is hard to have confidence in the validation process. In addition, the risk calculation that depends on multiplying SNP risks by Gail raises its own questions of accuracy. Finally, there is no prospective evidence that BREVAgen produces clinical evidence.

Darabi H, Czene K, Zhao W et al. Breast cancer risk prediction and individualised screening based on common genetic variation and breast density measurement. Breast Cancer Res 2012; 14(1):R25.
Armstrong K, Handorf EA, Chen J et al. Breast cancer risk prediction and mammography biopsy decisions: a model-based study. Am J Prev Med 2013; 44(1):15-22.
Mealiffe ME, Stokowski RP, Rhees BK et al. Assessment of clinical validity of a breast cancer risk model combining genetic and clinical information. J Natl Cancer Inst 2010; 102(21):1618-27.
Zheng W, Wen W, Gao YT et al. Genetic and clinical predictors for breast cancer risk assessment and stratification among Chinese women. J Natl Cancer Inst 2010; 102(13):972-81.
Campa D, Kaaks R, Le Marchand L et al. Interactions between genetic variants and breast cancer risk factors in the Breast and Prostate Cancer Cohort Consortium. J Natl Cancer Inst 2011.
Wacholder S, Hartge P, Prentice R et al. Performance of common genetic variants in breast-cancer risk models. N Engl J Med 2010; 362(11):986-93.

For Lay version see here

T-SPOT TB test – pro

M Levin, MD — Fri, 11 Oct 2013 19:37:24 +0000

T-SPOT is an assay used for tuberculosis diagnosis. It which belongs to the group of interferon-gamma release assays. The test is manufactured by Oxford Immunotec in the UK.and it counts the number of anti-mycobacterial effector T cells, white blood cells that produce interferon-gamma, in a sample of blood. This gives an overall measurement of the host immune response against mycobacteria, which can reveal the presence of infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB).

The important question is how it compares to the simple and widely available skin tuberculin test. Initial studies indicated a sensitivity of 97.2%. However, more recent data from a study in children with active TB disease in the UK suggest that the sensitivity of the T-SPOT.TB may in fact be worse than that of the tuberculin skin test (sensitivity reported as 66% and 82%, respectively)..A metaanalysis of studies in children with active tuberculosis published in 2011 suggests that the sensitivity of the T-SPOT.TB is very similar(but not superior) to that of the tuberculin skin test (pooled sensitivity reported as 84% and 80%, respectively).

Although superiority to skin tubeculin test is not yet established, FDA approved IGRAS test and T0SPot blood tests and the CDC guideline recommends their use. “….. TSTs and IGRAs (QFT-G, QFT-GIT, and T-Spot) may be used as aids in diagnosing M. tuberculosis infection,” the guidelines authors write. “They may be used for surveillance purposes and to identify persons likely to benefit from treatment. Multiple additional recommendations are provided that address quality control, test selection, and medical management after testing.”

As such, this is an FDA approved test but the reliable evidence shows that the expert consensus is that the farther clinical studies are still required. Prospective Comparison of the Tuberculin Skin Test and Interferon-Gamma Release Assays in Diagnosing Infection With Mycobacterium Tuberculosis and in Predicting Progression to Tuberculosis, NCT01622140.

Bamford, A. R J; Crook, A. M; Clark, J. E; Nademi, Z.; Dixon, G.; Paton, J. Y; Riddell, A.; Drobniewski, F. et al. (2009). Comparison of interferon- release assays and tuberculin skin test in predicting active tuberculosis (TB) in children in the UK: A paediatric TB network study”. Archives of Disease in Childhood 95 (3): 1806.

Ritz, Nicole; Connell, Tom G.; Paxton, Georgia A.; Buttery, Jim P.; Curtis, Nigel; Ranganathan, Sarath C. (2008). “A Three-Way Comparison of Tuberculin Skin Testing, QuantiFERON-TB Gold and T-SPOT.TB in Children”. In Dheda, Keertan. PLoS ONE 3 (7): e2624.

Connell, Thomas G.; Tebruegge, Marc; Ritz, Nicole; Bryant, Penelope A.; Leslie, David; Curtis, Nigel (2010). “Indeterminate Interferon- Release Assay Results in Children”. The Pediatric Infectious Disease Journal 29 (3): 2856.

Jump up ^ Connell, T. G.; Tebruegge, M.; Ritz, N.; Bryant, P.; Curtis, N. (2010). “The potential danger of a solely interferon- release assay-based approach to testing for latent Mycobacterium tuberculosis infection in children”. Thorax 66 (3): 2634

Mandalakas, A. M.; Detjen, A. K.; Hesseling, A. C.; Benedetti, A.; Menzies, D. (2011). “Interferon-gamma release assays and childhood tuberculosis: Systematic review and meta-analysis”. The International Journal of Tuberculosis and Lung Disease 15 (8): 101832.

Bone marrow aspiration and biopsy for fevers – pro

M Levin, MD — Thu, 10 Jan 2013 19:56:14 +0000

A bone marrow aspiration and biopsy is not the appropriate test for workup of fever that is not FUO. Instead, cacner, infection or autoimmune disease should be sought. The medically necessary approach to rule out a suspected lymphoma, for example, involves locating a lymph area that may be invovled. This test remains important in investigating fever of unknown origin, which, however, is by definition prolonged and unexplained after appropriate clincial and radiologic approaches. Bone marrow aspiration should not be used early or routinely to investigate fevers.

In one recent study looking at the role of this procedure in patients in India, where granulomatous diseases are more common than in the USA, 121 patients with pyrexia of unknown origin underwent both bone marrow aspiration and trephine biopsy as a part of diagnostic work-up. Bone marrow aspiration was diagnostic in only 16.5% of cases, which revealed leishmaniasis or pure red cell aplasia. Granulomas were infrequent in marrow aspiration smears, as only two cases (1.6%) showed ill defined epithelioid cell collections. Compared to this, trephine biopsy offered a diagnosis in 76% of the cases. Granulomas were a frequent finding in the trephine biopsy, being present in 70% of the cases included. Additional cases diagnosed on biopsy (over those diagnosed with aspiration smears) included lymphoma, tuberculosis, fungal infection, sarcoidosis and hypocellular marrow.

Gupta R, Setia N, Arora P, Singh S, Singh T, Hematological profile in pyrexia of unknown origin: role of bone marrow trephine biopsy vis-à-vis aspiration.Hematology. 2008 Oct;13(5):307-12.

http://haematologyireland.org/meetings/documents/Lymphoma-GuidelinesonDiagnosisandTreatmentofMalignantLymphomas.pdf

.Oussama Abla, MD, Jeremy Friedman, and John Doyle,Performing bone marrow aspiration and biopsy in children: Recommended guidelines Paediatr Child Health. 2008 July; 13(6): 499–501

For Lay version see here

About Fever of Uknown Origin(FUO)

PET for FUO

NMP-22 urine assays for bladder cancer – pro

M Levin, MD — Fri, 21 Dec 2012 17:53:42 +0000

NMP-22 urine assays for bladder cancer detect nuclear mitotic apparatus protein 1 (NUMA-1) using monoclonal antibodies. NMP-22 protein provides structural support for the nucleus and ensures the correct separation of genetic material during mitosis into the respective daughter cells through mitotic spindle stabilization. It is not a particularly specific tests, with many described non-cancer factors that elevate its values, and there is ongoing controversy as to whether its advantages in sensitivity over urine cytology are sufficient to recommend it as a routine screening test for bladder cancer.

Medicare has granted this test a CLIA exception but there are no guidelines that support its use at this time.

Huber S, Schwentner C, Taeger D, Pesch B, Nasterlack M, Leng G, Mayer T, Gawrych K, Bonberg N,

Pelster M, Johnen G, Bontrup H, Wellhäußer H, Bierfreund HG, Wiens C, Bayer C, Eberle F,

Scheuermann B, Kluckert M, Feil G, Brüning T, Stenzl A: UroScreen Study Group. Nuclear matrix protein-22: a prospective evaluation in a population at risk for bladder cancer. Results from the UroScreen study. BJU Int 2012, 110(5):699-708

Todenhöfer T, Hennenlotter J, Witstruk M, Gakis G, Aufderklamm S, Kuehs U, Stenzl A, Schwentner C: Influence of renal excretory function on the performance of urine based markers to detect bladder cancer. J Urol 2012, 187(1):68-73.

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Electromagnetic Navigation Bronchoscopy – pro

M Levin, MD — Sun, 16 Dec 2012 20:06:39 +0000

ENB (Electromagnetic Navigation Bronchoscopy) or EMN bronchoscopy is a type of bronchoscopy that uses electromagnetic guidance to project catheters into and through bronchial passages. Using a virtual, three-dimensional (3D) bronchial map from a recent CT scan and disposable catheters, it makes it possible to navigate to a desired location within the lung and to look at it or biopsy it, stage lymphatic nodes or to insert markers to guide future radioatherapy. FDA cleared it in 2004 through the 510(k) process. One prospective study concluded that there is a “yield/procedure [rate at] 74% and 100% for peripheral lesions and lymph nodes, respectively.” A diagnosis was obtained in 80.4% of bronchoscopic procedures. The second study found an overall 62.5% diagnostic. There are also a number of other series and non-randomized studies. The only randomized study was by Eberhardt et al (2007c) that compared the diagnostic yield of electromagnetic navigation bronchoscopy, endobronchial ultrasound and a combined procedure in 120 patients with peripheral lung lesions or solitary lung nodules on CT scans. Eelectromagnetic navigation bronchoscopy had a lower diagnostic yield (59 %) than endobronchial ultrasound (69 %). However, the combined procedure had a higher diagnostic yield (88 %) than either procedure alone. There was significantly diminished diagnosic yield (29 %) in the lower lobes with electromagnetic navigation bronchoscopy.

The British Thoracic Society guidelines for advanced diagnostic and therapeutic flexible bronchoscopy in adults (Du Rand et al, 2011) said that electromagnetic bronchoscopy may be considered for the biopsy of peripheral lesions or to guide trans-bronchial needle aspiration for sampling mediastinal lymph nodes (grade D). A grade “D” recommendation is based on evidence level 3 or level 4, or extrapolated evidence from studies rated as 2+ (level 3 refers to non-analytic studies, e.g., case reports, case series; level 4 refers to expert opinion; and level 2+ refers to well-conducted case-control or cohort studies with a low-risk of confounding, bias or chance, and a moderate probability that the relationship is causal). It is a fairly low level of confidence recommendation and not a USA guideline.

D.Makris et al, Electromagnetic navigation diagnostic bronchoscopy for small peripheral lung lesions ERJ June 1, 2007 vol. 29 no. 6 1187-1192

Andrew R. Haas Anil Vachani and Daniel H. Sterman Advances in Diagnostic Bronchoscopy Am. J. Respir. Crit. Care Med. 2010 182:589-597

Eberhardt R, Anantham D, Ernst A, et al. Multimodality bronchoscopic diagnosis of peripheral lung lesions. Am J Respir Crit Care Med. 2007c;176:36-41.

Daryl Phillip Pearlstein et al, Electromagnetic Navigation Bronchoscopy Performed by Thoracic Surgeons: One Center’s Early Success Ann. Thorac. Surg. 2012 93:944-950

Du Rand IA, Barber PV, Goldring J, et al; BTS Interventional Bronchoscopy Guideline Group. British Thoracic Society guideline for advanced diagnostic and therapeutic flexible bronchoscopy in adults. Thorax. 2011;66(3)::iii1-iii21. Available at: http://www.brit-thoracic.org.uk/Portals/0/Guidelines/BronchoscopyGuidelines/BTS%20Advanced%20Bronchoscopy%20guideline%20November%202011.pdf.

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Colovantage test for colon cancer – pro

M Levin, MD — Sun, 28 Oct 2012 16:09:25 +0000

ColoVantage is a new test available from Quest. It is a screening test that is not meant to be a substitute for colonoscopy. It was approved by NY State in March of 2011. It detects circulating methylated DNA from the SEPT9 gene, which is involved in cytokinesis and cell cycle control. A case-control study performed at Quest Diagnostics showed that the ColoVantage test is 70% sensitive for CRC detection at a specificity of 89%. ColoVantage has successfully detected cancer at all stages; however, the number of patients at each stage of cancer was too small to derive stage-specific sensitivity data. A similar test demonstrated a sensitivity of 67% and a specificity of 88% in a prospective study of almost 8000 people. Unfortinately, at this time, it remains a proprietary test that has not been sufficiently studied. These findings need to be confirmed in larger studies that evaluate the clinical utility of this test. Support for this test in guidelines from professional organizations is lacking.

Rösch T, Church T, Osborn N, et al. Prospective clinical validation of an assay for methylated SEPT9 DNA for colorectal cancer screening in plasma of average risk men and women over the age of 50 [abstract]. Gut. 2010;59(suppl III):A307.

deVos T, Tetzner R, Model F, Weiss G, Schuster M, Distler J, et al. Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin Chem. 2009 Jul;55(7):1337-46.

Tänzer M, Balluff B, Distler J, Hale K, Leodolter A, Röcken C, et al. Performance of epigenetic markers SEPT9 and ALX4 in plasma for detection of colorectal precancerous lesions. PLoS One. 2010 Feb 4;5(2):e9061.

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Cytogenetics and flow cytometry in diagnosis of CLL – pro

M Levin, MD — Mon, 17 Sep 2012 20:08:39 +0000

Chronic lymphocytic leukemia displays a characteristic patterns of surface antigen expression (CD antigens), which facilitate their identification and proper classification and hence play an important role in instituting proper treatment plans. Multiparameter flow cytometric analysis has become commonplace in most laboratories for that purpose. Distinction between lymphoid and myeloid leukemias and of various subtypes of chronic lymphoproliferative disorders is crucially important. Several advances in flow cytometry, including availability of new monoclonal antibodies, improved gating strategies, and multiparameter analytic techniques, have all dramatically improved the utility of flow cytometry in the diagnosis and classification of leukemia.

Flow cytometery is very helpful in a diagnosis of any leukemic condition and can be diagnostic of CLL by showing CD5 positivity, especially when joined with CD19 and 20 in a multigated analysis. Flow cytometery represents one of several sources of information that go into making a secure diagnosis. It should not be relied on in isolation to make a diagnosis.

The role for cytogenetics once CLL is diagnosed in more complex. It can support the diagnosis by confirming abnormalities tyoical of CLL and also can provide prognostic information. A recent European guideline says: “Molecular cytogenetic analysis via fluorescent in situ hybridization (FISH) for the detection of unfavourable prognostic factors like deletions on chromosome 17p or 11q is recommended as a diagnostic procedure prior first-line treatment. The usage of unmutated VH status, VH 3.21 usage, ZAP70- and CD38 expression, serum markers like CD23, thymidine kinase and ß2-microglobuline for routine assessment is not advised. Further clinical trials are requested to standardize these prognostic markers and develop them to useful instruments in clinical practice.”

Salem DA, Stetler-Stevenson M. Clinical Flow-Cytometric Testing in Chronic Lymphocytic Leukemia. Methods Mol Biol. 2019;2032:311-321. doi: 10.1007/978-1-4939-9650-6_17. PMID: 31522426.

Rawstron AC, Kreuzer KA, Soosapilla A, et al. Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry: An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project. Cytometry B Clin Cytom. 2018;94(1):121-128. doi:10.1002/cyto.b.21595

D’Archangelo M. Flow cytometry: new guidelines to support its clinical application.
Cytometry B Clin Cytom. 2007 May;72(3):209-10.

Eichhorst B, Dreyling M, Robak T, Montserrat E, Hallek M, ESMO Guidelines Working Group. Chronic lymphocytic leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011 Sep. 22 Suppl 6:vi50-4

Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008; 111:5446.

NCCN.ORG, CLL 2012

Cytogenetics and flow in diagnosis of myeloproliferative disorders – pro

M Levin, MD — Mon, 17 Sep 2012 20:07:04 +0000

Chronic myeloproliferative disorders (CMPD) are classified according to the WHO classification of 2001 as polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF), essential thrombocythemia (ET), CMPD/unclassifiable (CMPD-U), chronic neutrophilic leukemia, and chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome, all to be delineated from BCR/ABL-positive chronic myeloid leukemia (CML). I consider both cytogenetics and flow as not med. appropriate for diagnosis of CMPD. Clonal aberrations are found in 10% of patients with suspected CMPD establishing the diagnosis of a malignant disease but not allowing a secure diagnosis of any particular type of CMPD. A bone marrow would need to be repeated for that to be accomplished.

Cytogenetics are potentially more useful but only if they demonstrate a Philadelphia chromosome. Nowadays, PCR for BRC/ABL is the preferred test to do that and it can be performed on the marrow as well as blood. While some recent articles claim that one or another combination of cytogenetics and flow with other factors can diagnose CMPD, this has not been confirmed in prospective studies or recommended by guidelines. JAK2 mutation is more valuable than either of these two tests.

van de Loosdrecht AA, Alhan C, Béné MC, Della Porta MG, Dräger AM, Feuillard J, et al. Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on FCM in MDS. Haematologica. 2009;94:1124–34.

Osteocalcin and bone metastases – pro

M Levin, MD — Mon, 17 Sep 2012 20:03:51 +0000

Osteocalcin is a noncollagenous protein found in bone and dentin. It is secreted by osteoblasts and thought to play a role in mineralization and calcium ion homeostasis. It As osteocalcin is manufactured by osteoblasts, it is often used as a biochemical marker, or biomarker, for the bone formation process. Most of the use has been for monitoring treatment for osteoporosis but some use it for following metastatic bone disease. There are no guideline or consensus recommendations supporting this test for routine use.

Seregni E, Martinetti A, Ferrari L, et al: Clinical utility of biochemical marker of bone remodelling in patients with bone metastases of solid tumors. Q J Nucl Med 2001; 45(1):7-17.

Brown JP, Josse RG, & Scientific Advisory Council of the Osteoporosis Society of Canada: 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. CMAJ 2002; 167(10 Suppl):S1-S34.

Yoichi Arai et al, Osteocalcin: Is it a useful marker of bone metastasis and response to treatment in advanced prostate cancer? The Prostate Volume 20 Issue 3, Pages 169 – 177

http://www.jsnm.org/files/paper/anm/ams163/ANM16-3-01.pdf

Posted by M L on September 25, 2009 | Permalink|Comments (0)|TrackBack (0)

Previstage GCC Colon Cancer Staging Test

Traditional methods of examining lymph nodes (LNs) for metastases involve microscopically examining hematoxylin and eosin (H&E) stained 5µm sections of each LN. However, this method has important limitations. Previstage™ GCC Colorectal Cancer Staging Test attempts to overcome problems with sampling errors, marker specificity and persistence of expression in CRC and metastases. Using ultrasensitive quantitative RT-PCR, the assay interrogates the patient’s lymph nodes to identify levels of GCC consistent with that found in LNs with histologically-confirmed, clinically significant metastases from stage III CRC patients.

This is a new and yet unproven method of lymph node sampling It may be superior to traditional methods of sampling but that needs to be proven and clincial benefit confirmed. Currently, I consider it to be investigational.
Alex Mejia and Scott A Waldman Previstage™ GCC test for staging patients with colorectal cancer Expert Review of Molecular Diagnostics September 2008, Vol. 8, No. 5, Pages 571-578

Prostate Px – pro

M Levin, MD — Mon, 17 Sep 2012 19:59:10 +0000

This approach represents a cutting edge of diagnostic science, sometimes termed, “Personalized Medciine”. The concept that one can individualize cancer therpay based on specific tumor characteristics is attractive but needs to be proven before being widely adapted. As of now, there is little evidence to support it and no guidelines or professional bodies recommending it.

The approach relies on published information but the way it is put together and validated is not confirmed in studies or accepted in the medical community. From the manufacturer: Prostate Px provides several endpoints which assess disease severity and disease recurrence, including:

Px SCORE™
Disease Progression (metastasis, progression through ADT)
Favorable Pathology
Relative Risk of Disease (outcome compared to test’s validation cohort)
The power of Prostate Px results from its comprehensive analysis of the cancer tissue obtained from each patient. Clinical data is integrated with an exhaustive analysis of each patient’s cancer using spatial analysis of tissue histology and examining molecular biomarkers, such as androgen receptor, associated with disease progression.

An advanced mathematical approach is applied to a large patient cohort to generate a personalized report that is sent to the physician for discussion with the patient.

This processand information remains proprietary and not peer-reviewed.