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Tumor-associated autoantibodies correlate with poor outcome in prostate cancer patients treated with androgen deprivation and external beam radiation therapy.

Johnson LD, Nesslinger NJ, Blood PA, Chima N, Richier LR, Ludgate C, Pai HH, Lim JT, Nelson BH, Vlachaki MT, Lum JJ - Oncoimmunology (2014)

Bottom Line: Patients with non-metastatic prostate cancer received external beam radiation therapy (EBRT) plus neoadjuvant and concurrent androgen deprivation.Treatment-induced autoantibodies were detected in almost a third of patients receiving combinatorial ADT and EBRT.Thus, tumor-reactive autoantibodies may be associated with increased risk of biochemical failure and immunomodulation to prevent autoantibody development may improve BFFS for select, high-risk prostate cancer patients receiving both ADT and EBRT.

View Article: PubMed Central - PubMed

Affiliation: Trev and Joyce Deeley Research Centre; Victoria, BC Canada.

ABSTRACT
Standard cancer treatments trigger immune responses that may influence tumor control. The nature of these responses varies depending on the tumor and the treatment modality. We previously reported that radiation and androgen-deprivation therapy (ADT) induce tumor-associated autoantibody responses in prostate cancer patients. This follow-up analysis was conducted to assess the relationship between autoantibody responses and clinical outcome. Patients with non-metastatic prostate cancer received external beam radiation therapy (EBRT) plus neoadjuvant and concurrent androgen deprivation. Treatment-induced autoantibodies were detected in almost a third of patients receiving combinatorial ADT and EBRT. Unexpectedly, patients that developed autoantibody responses to tumor antigens had a significantly lower 5-year biochemical failure-free survival (BFFS) than patients that did not develop an autoantibody response. Thus, tumor-reactive autoantibodies may be associated with increased risk of biochemical failure and immunomodulation to prevent autoantibody development may improve BFFS for select, high-risk prostate cancer patients receiving both ADT and EBRT.

No MeSH data available.


Related in: MedlinePlus

Figure 2. Treatment-associated autoantibody responses correlate with increased likelihood of biochemical failure. Kaplan-Meier analysis of biochemical failure-free survival according to development of an autoantibody response. Sera from prostate cancer patients (n = 23) receiving androgen-deprivation and external beam radiation bimodal therapy were evaluated for the presence of autoreactive antibodies and plotted according to biochemical failure, as indicated by elevated prostate specific antigen (PSA). Autoantibody-positive subjects are indicated with a solid line and autoantibody-negative subjects are indicated with a dashed line. Check marks indicate censored subjects. A log-rank test was performed to determine the P value.
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Figure 2: Figure 2. Treatment-associated autoantibody responses correlate with increased likelihood of biochemical failure. Kaplan-Meier analysis of biochemical failure-free survival according to development of an autoantibody response. Sera from prostate cancer patients (n = 23) receiving androgen-deprivation and external beam radiation bimodal therapy were evaluated for the presence of autoreactive antibodies and plotted according to biochemical failure, as indicated by elevated prostate specific antigen (PSA). Autoantibody-positive subjects are indicated with a solid line and autoantibody-negative subjects are indicated with a dashed line. Check marks indicate censored subjects. A log-rank test was performed to determine the P value.

Mentions: The median follow-up time (the time from the end of treatment to the last available PSA value or death) was 73 mo (range 18–108 mo). Nine patients (39.1%) experienced biochemical failure. Specifically, 5 of 7 autoantibody-positive patients (71.4%) experienced BF compared with 4 of 16 autoantibody-negative patients (25%). By Kaplan-Meier analysis, patients who developed autoantibody responses during treatment showed a significantly higher rate of BF (Fig. 2; P = 0.025, hazard ratio [HR] = 5.99, 95% confidence interval [CI] 1.25–28.75). Multivariate analysis with risk group and autoantibody status indicated that neither risk group (P = 0.704, HR 1.342, 95% CI 0.294–6.126) nor the development of autoantibodies (P = 0.058, HR 4.283, 95% CI 0.954–19.224) was a significant independent predictor of BF (Table 2), although this is most likely due to the small number of patients in this study cohort.


Tumor-associated autoantibodies correlate with poor outcome in prostate cancer patients treated with androgen deprivation and external beam radiation therapy.

Johnson LD, Nesslinger NJ, Blood PA, Chima N, Richier LR, Ludgate C, Pai HH, Lim JT, Nelson BH, Vlachaki MT, Lum JJ - Oncoimmunology (2014)

Figure 2. Treatment-associated autoantibody responses correlate with increased likelihood of biochemical failure. Kaplan-Meier analysis of biochemical failure-free survival according to development of an autoantibody response. Sera from prostate cancer patients (n = 23) receiving androgen-deprivation and external beam radiation bimodal therapy were evaluated for the presence of autoreactive antibodies and plotted according to biochemical failure, as indicated by elevated prostate specific antigen (PSA). Autoantibody-positive subjects are indicated with a solid line and autoantibody-negative subjects are indicated with a dashed line. Check marks indicate censored subjects. A log-rank test was performed to determine the P value.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
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Figure 2: Figure 2. Treatment-associated autoantibody responses correlate with increased likelihood of biochemical failure. Kaplan-Meier analysis of biochemical failure-free survival according to development of an autoantibody response. Sera from prostate cancer patients (n = 23) receiving androgen-deprivation and external beam radiation bimodal therapy were evaluated for the presence of autoreactive antibodies and plotted according to biochemical failure, as indicated by elevated prostate specific antigen (PSA). Autoantibody-positive subjects are indicated with a solid line and autoantibody-negative subjects are indicated with a dashed line. Check marks indicate censored subjects. A log-rank test was performed to determine the P value.
Mentions: The median follow-up time (the time from the end of treatment to the last available PSA value or death) was 73 mo (range 18–108 mo). Nine patients (39.1%) experienced biochemical failure. Specifically, 5 of 7 autoantibody-positive patients (71.4%) experienced BF compared with 4 of 16 autoantibody-negative patients (25%). By Kaplan-Meier analysis, patients who developed autoantibody responses during treatment showed a significantly higher rate of BF (Fig. 2; P = 0.025, hazard ratio [HR] = 5.99, 95% confidence interval [CI] 1.25–28.75). Multivariate analysis with risk group and autoantibody status indicated that neither risk group (P = 0.704, HR 1.342, 95% CI 0.294–6.126) nor the development of autoantibodies (P = 0.058, HR 4.283, 95% CI 0.954–19.224) was a significant independent predictor of BF (Table 2), although this is most likely due to the small number of patients in this study cohort.

Bottom Line: Patients with non-metastatic prostate cancer received external beam radiation therapy (EBRT) plus neoadjuvant and concurrent androgen deprivation.Treatment-induced autoantibodies were detected in almost a third of patients receiving combinatorial ADT and EBRT.Thus, tumor-reactive autoantibodies may be associated with increased risk of biochemical failure and immunomodulation to prevent autoantibody development may improve BFFS for select, high-risk prostate cancer patients receiving both ADT and EBRT.

View Article: PubMed Central - PubMed

Affiliation: Trev and Joyce Deeley Research Centre; Victoria, BC Canada.

ABSTRACT
Standard cancer treatments trigger immune responses that may influence tumor control. The nature of these responses varies depending on the tumor and the treatment modality. We previously reported that radiation and androgen-deprivation therapy (ADT) induce tumor-associated autoantibody responses in prostate cancer patients. This follow-up analysis was conducted to assess the relationship between autoantibody responses and clinical outcome. Patients with non-metastatic prostate cancer received external beam radiation therapy (EBRT) plus neoadjuvant and concurrent androgen deprivation. Treatment-induced autoantibodies were detected in almost a third of patients receiving combinatorial ADT and EBRT. Unexpectedly, patients that developed autoantibody responses to tumor antigens had a significantly lower 5-year biochemical failure-free survival (BFFS) than patients that did not develop an autoantibody response. Thus, tumor-reactive autoantibodies may be associated with increased risk of biochemical failure and immunomodulation to prevent autoantibody development may improve BFFS for select, high-risk prostate cancer patients receiving both ADT and EBRT.

No MeSH data available.


Related in: MedlinePlus