Jump to content

The Histoculture Drug Response Assay (HDRA)


Recommended Posts

A study just released in the Journal of Thoracic Oncology shows it is possible to screen lung cancer patients for a sensitivity to certain chemotherapy drugs and then individualize their drug therapies for better outcomes.

The five-year survival rate for lung cancer patients who showed sensitivity to two of the chosen chemotherapy drugs was 82.4% compared to just 40.1% survival rate for patients whose tests revealed little or no sensitivity.

The HDRA (Histoculture Drug Response) Assay, which was used for this study is one of a number of "cell-death" assays. Cell death assays are broadly applicable to a wide range of human neoplasms, ranging from low response rate tumors (like pancreatic cancer and Cholangiocarcinoma) to high response rate tumors (like acute lymphoblastic leukemia, breast cancer and ovarian cancer). In cases where more than one acceptable regimen exists, the physician can select the regimen containing the most favorable drugs and avoid the regimen containing the most unfavorable drugs.

The main feature of the HDRA assay is three dimiensional (3D) culture which determines both drug sensitivity and resistance. Real life 3D analysis makes the HDRA assay indicative of what will happen in the body.


Background: In this study, we analyzed the usefulness of adjuvant chemotherapy for non-small cell lung cancer based on the histoculture drug response assay (HDRA).

Methods: From September 2001 to December 2008, 65 patients with pathologic stage II or higher non-small cell lung cancer who underwent surgery received two-cycle HDRA-based adjuvant chemotherapy. Chemosensitivity to cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabine, and irinotecan was examined by the HDRA. All patients were classified according to the number of administered HDRA-positive drugs: the prediction-sensitive group (PSG) (n = 31) comprised patients treated with two HDRA-positive drugs and the prediction-nonsensitive group (PNSG) (n = 34) comprised those treated with a combination of one HDRA-positive and one HDRA-negative drug or two HDRA-negative drugs. The clinical outcomes of the two groups were analyzed.

Results: The overall 5-year survival rate of the PSG was 82.4%. On the other hand, that of the PNSG was 40.1%. There were significant differences between the two groups (p = 0.03). The 5-year disease-free survival rate was more favorable in the PSG than in the PNSG (PSG: 56.5%, PNSG: 30.1%, p = 0.05). Multivariate analysis showed that chemotherapy based on the HDRA was a significant prognostic factor (p = 0.03).

Conclusions: The prognosis of patients treated with two HDRA-positive drugs was significantly better than that of those treated with one HDRA-positive drug or HDRA-negative drugs. Adjuvant chemotherapy based on the in vitro HDRA may be useful to improve survival in patients who have undergone surgery.

Source: Journal of Thoracic Oncology: September 2010 - Volume 5 - Issue 9 - pp 1376-1381doi:10.1097/JTO.0b013e3181e7d035

Link to comment
Share on other sites

There isn't one paper, or two, which by itself, makes a case for or against cell-based assays. Nor does the proposition that the whole thing depends on one study or even one review. You've got to consider the body of literature as a whole.

The fact that none of this exists as one neat, convenient paper in the New England Journal of Medicine does not, in any way, negate the existence of this body of information. It has been found that newer methods of "cell-death" assays have an overall predictive accuracy of 98.2% concerning treatment response, which compares favorably with older, previously published data ranging from 75% to 92%. (Staib,P.et al. Br J Haematol 128 (6):783-781, March 2005)

We have tests such as estrogen receptor, progesterone receptor, Her2/neu, BCR-ABL, C-KIT, CD-20, etc., and panels of immunohistochemical stains for subclassifying tumors. All of these tests are used to select chemotherapy in precisely the same manner as cell culture assay tests are used.

Also, we have the use of additional medical tests, such as serial CT, MRI, and PET scans, performed for the purpose of monitoring the size of the tumor to determine if it is shrinking or growing with chemotherapy. The purpose of this testing is to determine if chemotherapy with specific drugs should be continued or changed to different drugs. These radiographic tests are also used as an aid in making clinical decisions about the choice of chemotherapy.

So yes, there is precedent for using cell culture assays.

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?"

Why is it that oncologists are so accepting of high tech, expensive imaging studies, yet so reluctant to consider the use of cell culture diagnostic tests? For one thing, clinical trials virtually always have time to disease progression as a primary endpoint. Without the imaging studies, one can't get accurate time to progression data. So these are tests performed for the benefit of drug companies seeking new drug approval, for clinical investigators seeking contracts and publications, and for clinicians seeking an easy way to make clinical decisions (and, occasionally, seeking income enhancement).

In the absence of information provided by cell culture testing, oncologists have complete freedom to choose between a myriad of drug regimens. The proven basis on which they make these selections, by and large, is on the benefit a given regimen provides to the oncologist (or academic institution). Cell culture testing threatens this freedom of choice. There's absolutely nothing in it for the oncologist or academic medical center (unlike, for example, imaging studies).

Link to comment
Share on other sites

Join the conversation

You can post now and register later. If you have an account, sign in now to post with your account.

Reply to this topic...

×   Pasted as rich text.   Restore formatting

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.

  • Create New...

Important Information

By using this site, you agree to our Terms of Use. We have placed cookies on your device to help make this website better. You can adjust your cookie settings, otherwise we'll assume you're okay to continue.