Eureka! accurate prediction of individual patients response to specific therapies

[Lani]

ABSTRACT: Pharmacogenomic Predictor of Sensitivity to Preoperative Chemotherapy With Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide in Breast Cancer [Journal of Clinical Oncology; Subscribe; Sample]
Purpose: We developed a multigene predictor of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil-doxorubicin-cyclophosphamide (T/FAC) chemotherapy and assessed its predictive accuracy on independent cases.

Patients and methods: One hundred thirty-three patients with stage I-III breast cancer were included. Pretreatment gene expression profiling was performed with oligonecleotide microarrays on fine-needle aspiration specimens. We developed predictors of pCR from 82 cases and assessed accuracy on 51 independent cases.

Results: Overall pCR rate was 26% in both cohorts. In the training set, 56 probes were identified as differentially expressed between pCR versus residual disease, at a false discovery rate of 1%. We examined the performance of 780 distinct classifiers (set of genes + prediction algorithm) in full cross-validation. Many predictors performed equally well. A nominally best 30-probe set Diagonal Linear Discriminant Analysis classifier was selected for independent validation. It showed significantly higher sensitivity (92% v 61%) than a clinical predictor including age, grade, and estrogen receptor status. The negative predictive value (96% v 86%) and area under the curve (0.877 v 0.811) were nominally better but not statistically significant. The combination of genomic and clinical information yielded a predictor not significantly different from the genomic predictor alone. In 31 samples, RNA was hybridized in replicate with resulting predictions that were 97% concordant.

Conclusion: A 30-probe set pharmacogenomic predictor predicted pCR to T/FAC chemotherapy with high sensitivity and negative predictive value. This test correctly identified all but one of the patients who achieved pCR (12 of 13 patients) and all but one of those who were predicted to have residual disease had residual cancer (27 of 28 patients).

[Mary Jo]

Thanks for sharing - BUT - that's all greek to me.


:-) Mary Jo

[CLTann]

From the jargon the authors used, my interpretation is that the research did not fare well. It was a marginal and disputable method of prediction.

Ann

[Lani]

The abstract states "This test correctly identified all but one of the patients who achieved pCR (12 of 13 patients) and all but one of those who were predicted to have residual disease had residual cancer (27 of 28 patients)" Although the numbers are small, it would be a very remote possibility that the occurence was just due to chance.

To help with the jargon: pCR is pathological complete response ie, when they look for cancer under the microscope after biopsying after neoadjuvant chemo ie, chemo given before any removal of the tumor other than an needle or core biopsy THEY CAN"T FIND ANY AND THEREFORE FEEL THE CHEMO/IMMUNO/HORMONAL therapy was extremely they also were accurate in all but one case when when predicting whom the therapy would have NO EFFECT ON.

What is it they say... close, but no cigar. Well, I'd say almost right on and a cigar is in order!

Just my opinion...

Will read the full article and eat my hat (and report back)if it appears less than newsworthy

[chrisy]

Lani,

I really appreciate the time and effort you put into finding and posting these studies. I don't have a science background, but I do try to understand what's being reported. If only they would report these things as debits and credits, i'd have it licked!

I interpreted this as follows:
They used data from 82 cases to compile the "best 30 list" of predictive factors. These were used to predict whether a patient would have a complete response to T/FAC chemotherapy or would have residual disease after this chemo?
The results showed that this 30 factor list analysis was highly accurate in predicting complete response or residual disease and more accurate than "other clinical factors" including age, grade and ER status was in predicting complete response and residual disease, (but residual disease prediction difference was not statistically significant).

The conclusion is that this "test" is a better predictor of response to this particular chemo, and if used, could spare people doing this chemo and having it not work(or steer them to other chemos).

Am I close?

[Becky]

You are right on Chrisy.

[mamacze]

Dear Lani,
I am always grateful when you share the findings of your literature searches. I am printing this article as I type to put in my fille...one never knows when info like this is needed and if it ever is, I can thank you for having it right at my fingertips.
And Becky's "right on" is like the Good Housekeeping seal of approval!
Love Kim from CT