Ctc?

[Rich66]

How many folks' oncs run the circulating tumor cell test?

[Mary Anne in TX]

I had one done, but had to ask for it. I don't know how many other of his patients have had one done. Ma

[Joan M]

Rich,

I was told by Sloan-Kettering that they do not believe that the CTC test is meaningful and therefore don't use it. Ditto, for New York Presbyterian Hospital/Weill Cornell Medical Center, also in NYC.

However, several women on this site have had a CTC test.

Joan

[bejuce]

I had one done at Stanford as part of a clinical trial.

[sassy]

My onc declined giving one.

[mmoons]

My onc said no...not reliable - yet.

[Lori R]

My onc was reluctant as she thought there would be insurance hassles.

I pushed for it and received a score of 1 at a time that I was dealing with a recurrance. Insurance paid the $600, so I felt very vindicated.

I pushed for it again and received another score of 1. This time insurance refused to pay and I had to argue with them for over a year. The insurance battle was very frustrating and emotionally exhausting.

I am reluctant to request another one unless I am willing to pay the $600 out of my pocket.

Since the standard tests do not work for me, I was grasping at some way to give me insights regarding disease progression.

If I recur, I might be willing to pay the $.

[pibikay]

CTC is news to us here

[gdpawel]

It would be important to develop a method of in vivo labelling of tumor cells in the circulation and to monitor their trafficking and homing to other sites. If these cells are viable and therefore able to disseminate, I think the most robust test to this end is to document their ability to metastasize.

There was a symposium in Washington DC in September of 2009, devoted entirely to the CTC technology. The cutoff is 5 tumor cells. Less than 5 means that things are going well. More than 5 means that things are going poorly. But you can see the difference between 4 and 6 is not all that great.

What they found out from that symposium was that it's perhaps useful as an adjunct to traditional methods for following tumor response, such as x-rays, blood tests, CTs, MRIs, history, physical exam, etc.

Some molecular tests do utilize living cells, but generally of individual cancer cells in suspension, sometimes derived from tumors and sometimes derived from circulating tumor cells. This was tried with the human clonogenic assay, which had been discredited long ago.

Again, traditionally, in-vitro (in lab) "cell-lines" have been studied in 2 dimensions (2D) which has inherent limitations in applicability to real life 3D in-vivo (in body) states.

[StephN]

The specific HER2 serum test is more widely used. I do get that a couple of times a year.

You might look up the Cell Search web site and see what they have to say, or if there is a patient liason phone line you could call.

[mamacze]

My oncologist just ordered the Veridex CellSearch Circulating Tumor Cell blood test. Quest offers the test. This is a nice plain English summary of the test:
http://www.oncbiz.com/interviews/pdf...AN09_OC_MC.pdf According to this article; Medicare also pays for it. I have just sent an insurance appeal to my local Connecticare insurance company to see if they will pay for it. I will keep you posted; re results..
Love Kim from CT

[Rich66]

Kim,
From what I've seen, the test might have the most utility for monitoring NED patients with long scan intervals.

[anna4969]

Hi Rich,

I asked my oncologist at MD Anderson for this test in May. She declined, with very much the same reasoning, unreliable. I still would like very much to have one, but now after this discussion, I would worry about being responsible for the $600 fee if insurance put up a fuss. Hope this info helps.

[Chelee]

I asked for a CTC for a few yrs and always got the same answer, "It's not prime time yet". But once I recurred and was stage IV I asked again...this time a bit more pushy about it. Plus I told my onc I'd be less likely to scan if both my CA27.29 & CTC came back the same...meaning both low, or both high.

My onc told me if my insurance will pay for it she will do it. Blue Cross did cover it, no doubt since I'm stage IV.

Chelee

[caya]

My onc. does not do it, same reason as most others - unreliable.

all the best
caya

[Lani]

GDPAWEL--I THINK THE INFO YOU RECEIVED AT THE 2009 MEETING IS DATED.

MANY PAPERS QUOTE ANY CTCS AS ABNORMAL, BUT OF COURSE IT DEPENDS ON THE TECHNOLOGY UTILIZED, WHICH IS EVOLVING

AT ASCO in June I frequented a booth of a company which is utilizing a non-magnetic technology to isolate the tumor cells and then phenotyping them (ER,PR, her2 status etc determined on the INDIVIDUAL cells) and said they would be available for the general public (and inferred FDA approved) within one month (that should be this upcoming week!)

Most papers correlate ctcs with treatment response and/or progression only in stage IVs, but some are using them to try to determine if adjuvant treatment in early stagers was efficacious.

Various platforms are being developed--besides the Veridex/J&J tehcnology based on magnetic beads with EpCam, there is the Adnar test (uses three antigens/markers), the Dana-Farber/Mass General technology, the Magnasweep technology developed by Stefanie Jeffrey at Stanford and this new technology--will try to unpack my long not-unpacked bag with handouts from ASCO and get the company name--among others.

Hope this helps!

[gdpawel]

Whatever will be more useful as an adjunct to traditional methods for following tumor response, such as x-rays, blood tests, CTs, MRIs, history, physical exam, etc. However, in regards to drug selection, analysis of a relatively small number of isolated cancer cells cannot yield the same quality information as subjecting living cells to chemotherapeutic agents, begging the question of whether or not it can accurately predict which drugs will work and which will not.

[Jackie07]

Below are five abstracts I just located via PubMed. A lot of interesting development has happened in the past few months:

Breast Cancer Res Treat. 2011 Jun 28. [Epub ahead of print]
Artificial neural network analysis of circulating tumor cells in metastatic breast cancer patients.
Giordano A, Giuliano M, De Laurentiis M, Eleuteri A, Iorio F, Tagliaferri R, Hortobagyi GN, Pusztai L, De Placido S, Hess K, Cristofanilli M, Reuben JM.
Source
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA, agiordano@mdanderson.org.
Abstract
A cut-off of 5 circulating tumor cells (CTCs) per 7.5 ml of blood in metastatic breast cancer (MBC) patients is highly predictive of outcome. We analyzed the relationship between CTCs as a continuous variable and overall survival in immunohistochemically defined primary tumor molecular subtypes using an artificial neural network (ANN) prognostic tool to determine the shape of the relationship between risk of death and CTC count and to predict individual survival. We analyzed a training dataset of 311 of 517 (60%) consecutive MBC patients who had been treated at MD Anderson Cancer Center from September 2004 to 2009 and who had undergone pre-therapy CTC counts (CellSearch(®)). Age; estrogen, progesterone receptor, and HER2 status; visceral metastasis; metastatic disease sites; therapy type and line; and CTCs as a continuous value were evaluated using ANN. A model with parameter estimates obtained from the training data was tested in a validation set of the remaining 206 (40%) patients. The model estimates were accurate, with good discrimination and calibration. Risk of death, as estimated by ANN, linearly increased with increasing CTC count in all molecular tumor subtypes but was higher in ER+ and triple-negative MBC than in HER2+. The probabilities of survival for the four subtypes with 0 CTC were as follows: ER+/HER2- 0.947, ER+/HER2+ 0.959, ER-/HER2+ 0.902, and ER-/HER2- 0.875. For patients with 200 CTCs, they were ER+/HER2- 0.439, ER+/HER2+ 0.621, ER-/HER2+ 0.307, ER-/HER2- 0.130. In this large study, ANN revealed a linear increase of risk of death in MBC patients with increasing CTC counts in all tumor subtypes. CTCs' prognostic effect was less evident in HER2+ MBC patients treated with targeted therapy. This study may support the concept that the number of CTCs, along with the biologic characteristics, needs to be carefully taken into account in future analysis.


Breast Cancer Res. 2011 Jun 23;13(3):R67. [Epub ahead of print]
Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment.

Giuliano M, Giordano A, Jackson S, Hess KR, De Giorgi U, Mego M, Handy BC, Ueno NT, Alvarez RH, De Laurentiis M, De Placido S, Valero V, Hortobagyi GN, Reuben JM, Cristofanilli M.
Abstract

ABSTRACT:
INTRODUCTION:

Circulating tumor cells (CTCs) represent an independent predictor of outcome in patients with metastatic breast cancer (MBC). We assessed the prognostic impact of CTCs according to different first-line systemic treatments, and explored their potential predictive value in MBC patients.
METHODS:

We retrospectively evaluated 235 newly diagnosed MBC patients, treated at the University of Texas MD Anderson Cancer Center. All patients had a baseline CTC assessment performed with CellSearch(R). Progression-free survival (PFS) and overall survival (OS) were compared with Log-Rank test between groups, according to CTC count (<5 vs. greater than or equal to 5) and type of systemic therapy. We further explored the predictive value of baseline CTCs in patients, receiving different treatments.
RESULTS:

At a median follow-up of 18 months CTC count was confirmed to be a robust prognostic marker in the overall population (median PFS: 12.0 months for patients with CTC <5 and and 7.0 months for those with CTCs greater than or equal to 5; P <.001). Conversely, in patients with HER-2 overexpressed/amplified tumors receiving trastuzumab or lapatinib, baseline CTC count was not prognostic (median PFS: 14.5 months for patients with <5 CTC and 16.1 months for those with CTCs greater than or equal to 5; P=.947). Furthermore, in patients with HER-2 normal tumors, a baseline CTC count greater than or equal to 5 identified subjects who derived benefit from more aggressive treatments, including combination chemotherapy and chemotherapy plus bevacizumab.
CONCLUSIONS:

This analysis suggests that the prognostic information provided by CTC count may be useful in patient stratifications and therapeutic selection, particularly in the group with positive CTCs, in which various therapeutic choices may procure differential palliative benefit.

Ann Oncol. 2011 Jun 3. [Epub ahead of print]
High independent prognostic and predictive value of circulating tumor cells compared with serum tumor markers in a large prospective trial in first-line chemotherapy for metastatic breast cancer patients.

Pierga JY, Hajage D, Bachelot T, Delaloge S, Brain E, Campone M, Diéras V, Rolland E, Mignot L, Mathiot C, Bidard FC.
Source

Department of Medical Oncology, Institut Curie, Paris.
Abstract

BACKGROUND:

Circulating tumor cells (CTCs) are a prognostic marker in metastatic breast cancer, but comparisons with serum tumor markers (CA 15-3, carcinoembryonic antigen and lactate dehydrogenase) variations are needed.
PATIENTS AND METHODS:

CTCs were counted with CellSearch® at baseline, before cycle 2 (C2) and cycle 3 or 4 (C3/4) in 267 metastatic breast cancer patients on first-line chemotherapy with/without targeted therapy.
RESULTS:

Baseline CTC detection rate was 65% with ≥1 CTC/7.5 ml threshold and 44% with ≥5 CTC/7.5 ml and was independent of subtypes (luminal, triple negative, human epithelial growth factor receptor 2 (HER2)+). CTCs were associated with tumor markers, bone/liver involvement, tumor burden and performance status. CTC detection ≥1 CTC/7.5 ml was a strong prognostic factor for progression-free survival (PFS), P < 0.0001. Threshold of CTC ≥5 was statistically significant for PFS and overall survival (OS), P = 0.03 on multivariate analysis. Among patients with ≥5 CTC/7.5 ml at baseline, 50% had <5 CTC/7.5 ml at C2. Changes were correlated with both PFS and OS (P < 0.0001). All patients receiving anti-HER2 therapy had <5 CTC/7.5 ml after three cycles of treatment.
CONCLUSION:

This is the largest prospective series validating the prognostic value of CTC independently from serum tumor marker. Elevated CTCs before C2 are an early predictive marker of poor PFS and OS, which could be used to monitor treatment benefit. CTC decrease under treatment seems stronger with targeted therapy.

Gynecol Oncol. 2011 May 21. [Epub ahead of print]
Comparison of estrogen and progesterone receptor status of circulating tumor cells and the primary tumor in metastatic breast cancer patients.

Aktas B, Müller V, Tewes M, Zeitz J, Kasimir-Bauer S, Loehberg CR, Rack B, Schneeweiss A, Fehm T.
Source

Department of Gynecology and Obstetrics, University of Essen, Hufelandstraße 55, 45122 Essen, Germany.
Abstract

OBJECTIVES:

The expression of predictive markers including the estrogen (ER) and progesterone receptor (PR) expression can change during the course of the disease. Therefore, reassessment of these markers at the time of disease progression might help to optimize treatment decisions. Metastatic tissue may be difficult to obtain for repeated analysis. In this context, characterization of circulating tumor cells (CTCs) could be of relevance. It was the purpose of the present study (1) to reevaluate the ER/PR expression by CTCs and (2) to compare the hormone receptor status expression profile of CTCs with the primary tumor.
METHODS:

We evaluated 193 blood samples from metastatic breast cancer patients at the time of first diagnosis of metastatic disease or disease progression. All samples underwent immunomagnetic enrichment using the AdnaTest BreastCancerSelect (AdnaGen AG, Germany) within 4h after blood withdrawal followed by RNA isolation and subsequent gene expression analysis by reverse transcription and Multiplex-PCR in separated tumor cells using the AdnaTest BreastCancerDetect. CTCs were analyzed for the three breast cancer-associated markers: EpCAM, Muc-1, Her-2 and actin as an internal PCR control. Expression of the ER and PR was assessed in an additional RT-PCR. The analysis of PCR products was performed by capillary electrophoresis on the Agilent Bioanalyzer 2100.
RESULTS:

The overall detection rate for CTCs was 45% (87/193 patients) with the expression rates of 71% for EpCAM (62/87 patients), 73% for MUC1 (64/87 patients), 48% for HER2 (42/87 patients), 19% for ER (17/87 patients) and 10% for PR (9/87 patients), respectively. Comparisons with the primary tumor were only performed in CTC+ patients (n=87). In 48/62 (77%) patients with ER+ tumors, CTCs were ER- and 46/53 (87%) patients with PR+ tumors did not express PR on CTCs. Primary tumors and CTCs displayed a concordant ER and PR status in only 41% (p=0.260) and 45% (p=0.274) of cases, respectively.

Breast Cancer Res Treat. 2011 May 12. [Epub ahead of print]
The influence of removal of primary tumor on incidence and phenotype of circulating tumor cells in primary breast cancer.
Banys M, Krawczyk N, Becker S, Jakubowska J, Staebler A, Wallwiener D, Fehm T, Rothmund R.
Source
Department of Obstetrics and Gynecology, University of Tuebingen, Calwerstrasse 7, 72076, Tuebingen, Germany, maggiebanys@yahoo.de.
Abstract
Recent studies have shown that the detection of circulating tumor cells (CTC) pre and postoperatively in the peripheral blood of primary breast cancer patients may be an indicator for poor survival. This study aimed to investigate the influence of removal of the primary tumor on incidence and phenotype of circulating tumor cells in primary breast cancer. 209 primary breast cancer patients could be included into this analysis. Blood sampling was performed both pre and postoperatively. The blood specimens were immunomagnetically enriched using AdnaTest BreastCancerSelect within 4 h after blood withdrawal, followed by RNA isolation and subsequent gene expression analysis by reverse transcription and multiplex PCR using AdnaTest BreastCancerDetect. Three breast cancer-associated tumor markers and two hormone receptor genes were amplified: GA733-2, Muc-1, Her-2, ER, PR. In addition, bone marrow (BM) status was intraoperatively determined. Forty-three of 209 patients (21%) had pre and/or postoperatively circulating tumor cells. The positivity rates after surgery were higher but did not differ significantly (12% pre and 16% postoperatively, P = 0.264). Disseminated tumor cells in BM were seen in 32 of 209 cases (15%). Patients with positive BM status had significantly higher CTC positivity rates both pre and postoperatively compared to those with negative BM status. The most common CTC phenotype was triple negative (24 patients) followed by HER2+/ER-/PR- subtype (10) and ER and/or PR positive (9). Interestingly, 41 of 43 primary tumors (95%) were ER and PR positive. Removal of the primary tumor did not alter the phenotype of CTC. Surgery does not significantly influence the tumor cell load in the blood stream. CTC phenotype before and after the surgery generally remains identical but may differ from that of the primary tumor.

[gdpawel]

The number of cells discovered in the CTC technique has turned out to be a good prognosticator of how well empiric treatments are working, and is proving to be highly complementary to the parellel breakthrough efforts in targeted therapy through cell function analysis. The blood test could obiate the need for repeatedly doing CT scans and biopsies to measure disease, the extent of disease and new mutations in people undergoing cancer treatment.

The June issue of Oncology News International (June 2010, V 19, No 6) quotes a Duke University study of the use of high-tech cancer imaging, with one representative finding being that the average Medicare lung cancer patient receives 11 radiographs, 6 CT scans, a PET scan, and MRI, two echocardiograms, and an ultrasound, all within two years of diagnosis. A study co-author (Dr. Kevan Schulman) asks: "Are all these imaging studies essential? Are they all of value? Is the information really meaningful? What is changing as a result of all this imaging?"

[Rich66]

I don't know..is that a way of suggesting they have no effective treatment for lung cancer?

But..it would seem no matter what information guides drug selection tools to monitor suggest when things are working or not. I wonder if CTCs won't turn out to be like other markers..helpful for some, useless for others.