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Evaluation of a chemoresponse assay as a predictive marker in the treatment of recurrent ovarian cancer: further analysis of a prospective study.

Tian C, Sargent DJ, Krivak TC, Powell MA, Gabrin MJ, Brower SL, Coleman RL - Br. J. Cancer (2014)

Bottom Line: Women with persistent or recurrent epithelial ovarian cancer (n=262) were empirically treated with one of 15 therapies, blinded to assay results.On the basis of 3000 simulations, the mean HR for mismatch was 0.81 (95% range=0.66-0.99), with 3.4% of HRs less than 0.67, indicating that HR for match is lower than for mismatch.These analyses provide supportive evidence that this chemoresponse assay is a predictive marker, demonstrating its ability to discern specific therapies that are likely to be more effective among multiple alternatives.

View Article: PubMed Central - PubMed

Affiliation: Precision Therapeutics, Inc., 2516 Jane Street, Pittsburgh, PA 15203, USA.

ABSTRACT

Background: Recently, a prospective study reported improved clinical outcomes for recurrent ovarian cancer patients treated with chemotherapies indicated to be sensitive by a chemoresponse assay, compared with those patients treated with non-sensitive therapies, thereby demonstrating the assay's prognostic properties. Due to cross-drug response over different treatments and possible association of in vitro chemosensitivity of a tumour with its inherent biology, further analysis is required to ascertain whether the assay performs as a predictive marker as well.

Methods: Women with persistent or recurrent epithelial ovarian cancer (n=262) were empirically treated with one of 15 therapies, blinded to assay results. Each patient's tumour was assayed for responsiveness to the 15 therapies. The assay's ability to predict progression-free survival (PFS) was assessed by comparing the association when the assayed therapy matches the administered therapy (match) with the association when the assayed therapy is randomly selected, not necessarily matching the administered therapy (mismatch).

Results: Patients treated with assay-sensitive therapies had improved PFS vs patients treated with non-sensitive therapies, with the assay result for match significantly associated with PFS (hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.50-0.91, P=0.009). On the basis of 3000 simulations, the mean HR for mismatch was 0.81 (95% range=0.66-0.99), with 3.4% of HRs less than 0.67, indicating that HR for match is lower than for mismatch. While 47% of tumours were non-sensitive to all assayed therapies and 9% were sensitive to all, 44% displayed heterogeneity in assay results. Improved outcome was associated with the administration of an assay-sensitive therapy, regardless of homogeneous or heterogeneous assay responses across all of the assayed therapies.

Conclusions: These analyses provide supportive evidence that this chemoresponse assay is a predictive marker, demonstrating its ability to discern specific therapies that are likely to be more effective among multiple alternatives.

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Related in: MedlinePlus

Two-dimensional clustering analysis based on chemoresponse assay data for single-agent treatments. Therapies are represented along the x axis, and patients are represented along the y axis. Red indicates lower assay score (i.e., sensitive), and yellow indicates higher assay score (i.e., resistant).
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fig4: Two-dimensional clustering analysis based on chemoresponse assay data for single-agent treatments. Therapies are represented along the x axis, and patients are represented along the y axis. Red indicates lower assay score (i.e., sensitive), and yellow indicates higher assay score (i.e., resistant).

Mentions: Chemoresponse assay scores for the seven single-agent therapies were further evaluated using two-dimensional clustering analysis. Therapies are represented along the x axis, with carboplatin, cisplatin and doxorubicin clustering together and paclitaxel, docetaxel, topotecan and gemcitabine clustering together. Along the y axis, patients were classified into three clusters (A, B and C), consisting of 63%, 36% and 1% of the study population, respectively (Figure 4). Cluster C was excluded from the analysis owing to the limited number of patients in this group. There is no evidence that this unsupervised clustering was significantly associated with either clinical characteristics or patient outcome (data not shown). These results, together with the data shown in Figure 3 and Table 2, indicate this assay is likely not prognostic of outcome independent of treatment, like some clinical factors (e.g., age, stage, grade, etc.). Rather, the assay's prognostic value (as observed in the mismatch analysis) is likely attributed to cross-drug response (i.e., correlation of assay results for randomly selected therapies with assay result for clinically administered therapy), as anticipated.


Evaluation of a chemoresponse assay as a predictive marker in the treatment of recurrent ovarian cancer: further analysis of a prospective study.

Tian C, Sargent DJ, Krivak TC, Powell MA, Gabrin MJ, Brower SL, Coleman RL - Br. J. Cancer (2014)

Two-dimensional clustering analysis based on chemoresponse assay data for single-agent treatments. Therapies are represented along the x axis, and patients are represented along the y axis. Red indicates lower assay score (i.e., sensitive), and yellow indicates higher assay score (i.e., resistant).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150278&req=5

fig4: Two-dimensional clustering analysis based on chemoresponse assay data for single-agent treatments. Therapies are represented along the x axis, and patients are represented along the y axis. Red indicates lower assay score (i.e., sensitive), and yellow indicates higher assay score (i.e., resistant).
Mentions: Chemoresponse assay scores for the seven single-agent therapies were further evaluated using two-dimensional clustering analysis. Therapies are represented along the x axis, with carboplatin, cisplatin and doxorubicin clustering together and paclitaxel, docetaxel, topotecan and gemcitabine clustering together. Along the y axis, patients were classified into three clusters (A, B and C), consisting of 63%, 36% and 1% of the study population, respectively (Figure 4). Cluster C was excluded from the analysis owing to the limited number of patients in this group. There is no evidence that this unsupervised clustering was significantly associated with either clinical characteristics or patient outcome (data not shown). These results, together with the data shown in Figure 3 and Table 2, indicate this assay is likely not prognostic of outcome independent of treatment, like some clinical factors (e.g., age, stage, grade, etc.). Rather, the assay's prognostic value (as observed in the mismatch analysis) is likely attributed to cross-drug response (i.e., correlation of assay results for randomly selected therapies with assay result for clinically administered therapy), as anticipated.

Bottom Line: Women with persistent or recurrent epithelial ovarian cancer (n=262) were empirically treated with one of 15 therapies, blinded to assay results.On the basis of 3000 simulations, the mean HR for mismatch was 0.81 (95% range=0.66-0.99), with 3.4% of HRs less than 0.67, indicating that HR for match is lower than for mismatch.These analyses provide supportive evidence that this chemoresponse assay is a predictive marker, demonstrating its ability to discern specific therapies that are likely to be more effective among multiple alternatives.

View Article: PubMed Central - PubMed

Affiliation: Precision Therapeutics, Inc., 2516 Jane Street, Pittsburgh, PA 15203, USA.

ABSTRACT

Background: Recently, a prospective study reported improved clinical outcomes for recurrent ovarian cancer patients treated with chemotherapies indicated to be sensitive by a chemoresponse assay, compared with those patients treated with non-sensitive therapies, thereby demonstrating the assay's prognostic properties. Due to cross-drug response over different treatments and possible association of in vitro chemosensitivity of a tumour with its inherent biology, further analysis is required to ascertain whether the assay performs as a predictive marker as well.

Methods: Women with persistent or recurrent epithelial ovarian cancer (n=262) were empirically treated with one of 15 therapies, blinded to assay results. Each patient's tumour was assayed for responsiveness to the 15 therapies. The assay's ability to predict progression-free survival (PFS) was assessed by comparing the association when the assayed therapy matches the administered therapy (match) with the association when the assayed therapy is randomly selected, not necessarily matching the administered therapy (mismatch).

Results: Patients treated with assay-sensitive therapies had improved PFS vs patients treated with non-sensitive therapies, with the assay result for match significantly associated with PFS (hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.50-0.91, P=0.009). On the basis of 3000 simulations, the mean HR for mismatch was 0.81 (95% range=0.66-0.99), with 3.4% of HRs less than 0.67, indicating that HR for match is lower than for mismatch. While 47% of tumours were non-sensitive to all assayed therapies and 9% were sensitive to all, 44% displayed heterogeneity in assay results. Improved outcome was associated with the administration of an assay-sensitive therapy, regardless of homogeneous or heterogeneous assay responses across all of the assayed therapies.

Conclusions: These analyses provide supportive evidence that this chemoresponse assay is a predictive marker, demonstrating its ability to discern specific therapies that are likely to be more effective among multiple alternatives.

Show MeSH
Related in: MedlinePlus