Abstract
Purpose/Objective: Proliferation of surviving tumor cells during fractionated radiotherapy may limit tumor control, especially in rapidly proliferating tumors. It has been widely accepted, that this may play a major role in head and neck tumors. Several methods for the assessment of tumor proliferation have been developed, however, most of them are either laborious, invasive or potentially toxic. Today, the gold standard is the flow cytometric BrdUrd assay. We present a flow cytometric method for detection of PCNA, which is an intranuclear proliferation associated protein, in solid human head and neck tumors and how these data correlate with outcome. Materials and Methods: Pretherapeutic biopsies of 20 inoperable patients with squamous cell carcinoma of the head and neck (T3-4N2M0) were examined. The tissue was disaggregated with pepsin/HCl, antibody staining was performed using the clone PC10. Biparametric flow cytometry was performed after a FITC conjugated secondary antibody and propidiumjodine staining was applied. The PCNA-index (i.e. percentage PCNA-positive cells), the DNA-index and the S-phase fraction (SPF, euploid tumors only) were determined. The therapy consisted of combined accelerated-hyperfractionated radiochemotherapy (66 Gy in 5 wks, concomittant boost of 1.6 Gy/d in wks 4+5, Carboplatin in wks 1+5). The median follow-up time was 14 mths (5 -
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Citation Formats
Wenz, F, Lohr, F, Rudat, V, Dietz, A, Flentje, M, and Wannenmacher, M.
Predictive value of the flow cytometric PCNA - assay (proliferating cell nuclear antigen) in head and neck tumors after accelerated-hyperfractionated radiochemotherapy.
United States: N. p.,
1995.
Web.
doi:10.1016/0360-3016(95)97878-5.
Wenz, F, Lohr, F, Rudat, V, Dietz, A, Flentje, M, & Wannenmacher, M.
Predictive value of the flow cytometric PCNA - assay (proliferating cell nuclear antigen) in head and neck tumors after accelerated-hyperfractionated radiochemotherapy.
United States.
https://doi.org/10.1016/0360-3016(95)97878-5
Wenz, F, Lohr, F, Rudat, V, Dietz, A, Flentje, M, and Wannenmacher, M.
1995.
"Predictive value of the flow cytometric PCNA - assay (proliferating cell nuclear antigen) in head and neck tumors after accelerated-hyperfractionated radiochemotherapy."
United States.
https://doi.org/10.1016/0360-3016(95)97878-5.
@misc{etde_20420729,
title = {Predictive value of the flow cytometric PCNA - assay (proliferating cell nuclear antigen) in head and neck tumors after accelerated-hyperfractionated radiochemotherapy}
author = {Wenz, F, Lohr, F, Rudat, V, Dietz, A, Flentje, M, and Wannenmacher, M}
abstractNote = {Purpose/Objective: Proliferation of surviving tumor cells during fractionated radiotherapy may limit tumor control, especially in rapidly proliferating tumors. It has been widely accepted, that this may play a major role in head and neck tumors. Several methods for the assessment of tumor proliferation have been developed, however, most of them are either laborious, invasive or potentially toxic. Today, the gold standard is the flow cytometric BrdUrd assay. We present a flow cytometric method for detection of PCNA, which is an intranuclear proliferation associated protein, in solid human head and neck tumors and how these data correlate with outcome. Materials and Methods: Pretherapeutic biopsies of 20 inoperable patients with squamous cell carcinoma of the head and neck (T3-4N2M0) were examined. The tissue was disaggregated with pepsin/HCl, antibody staining was performed using the clone PC10. Biparametric flow cytometry was performed after a FITC conjugated secondary antibody and propidiumjodine staining was applied. The PCNA-index (i.e. percentage PCNA-positive cells), the DNA-index and the S-phase fraction (SPF, euploid tumors only) were determined. The therapy consisted of combined accelerated-hyperfractionated radiochemotherapy (66 Gy in 5 wks, concomittant boost of 1.6 Gy/d in wks 4+5, Carboplatin in wks 1+5). The median follow-up time was 14 mths (5 - 28), the clinical partners (V.R., A.D.) were 'blinded' towards the PCNA-values. Results: 13 patients suffered from disease progession and 11 died. The actuarial median survival and disease free survival (DFS) were 14.4 and 10.7 mths, respectively. The PCNA-values ranged from 3.2 to 70% (median 9%), there were 7 aneuploid and 13 euploid tumors. SFP in the euploid tumors ranged from 4 to 14.5% (median 10.5%). Neither SFP nor ploidy had a significant influence on the outcome. The patients were divided according to their PCNA-value in higher (n=10) and lower (n=10) than the median. The survival and DFS were 13.1 and 7.6 mths for the group > 9% and both values were greater than 15 mths for the group <9%. The difference in DFS was significant (p = 0.03, log rank test). Conclusion: These results fall in line with other studies showing the influence of the pretherapeutic proliferation on the outcome after radiotherapy. However, there are several points to mention. This study was performed during a clinical trial of the efficacy of a moderately accelerated therapy regimen. This therapy certainly reduces the influence of the proliferation on the outcome, but as our results show, the patients with faster proliferating tumors still have a worse outcome. They have a shorter survival and DFS. The DFS, i.e. the time until progression, is the more relevant parameter in this study, because of various salvage therapies, which may influence overall survival. However, it is unlikely that one single parameter, in this case proliferation, will adequately predict the response to radiotherapy, although our patients represent a clinically homogeneous sample and received identical therapy.}
doi = {10.1016/0360-3016(95)97878-5}
journal = []
issue = {971}
volume = {32}
journal type = {AC}
place = {United States}
year = {1995}
month = {Jul}
}
title = {Predictive value of the flow cytometric PCNA - assay (proliferating cell nuclear antigen) in head and neck tumors after accelerated-hyperfractionated radiochemotherapy}
author = {Wenz, F, Lohr, F, Rudat, V, Dietz, A, Flentje, M, and Wannenmacher, M}
abstractNote = {Purpose/Objective: Proliferation of surviving tumor cells during fractionated radiotherapy may limit tumor control, especially in rapidly proliferating tumors. It has been widely accepted, that this may play a major role in head and neck tumors. Several methods for the assessment of tumor proliferation have been developed, however, most of them are either laborious, invasive or potentially toxic. Today, the gold standard is the flow cytometric BrdUrd assay. We present a flow cytometric method for detection of PCNA, which is an intranuclear proliferation associated protein, in solid human head and neck tumors and how these data correlate with outcome. Materials and Methods: Pretherapeutic biopsies of 20 inoperable patients with squamous cell carcinoma of the head and neck (T3-4N2M0) were examined. The tissue was disaggregated with pepsin/HCl, antibody staining was performed using the clone PC10. Biparametric flow cytometry was performed after a FITC conjugated secondary antibody and propidiumjodine staining was applied. The PCNA-index (i.e. percentage PCNA-positive cells), the DNA-index and the S-phase fraction (SPF, euploid tumors only) were determined. The therapy consisted of combined accelerated-hyperfractionated radiochemotherapy (66 Gy in 5 wks, concomittant boost of 1.6 Gy/d in wks 4+5, Carboplatin in wks 1+5). The median follow-up time was 14 mths (5 - 28), the clinical partners (V.R., A.D.) were 'blinded' towards the PCNA-values. Results: 13 patients suffered from disease progession and 11 died. The actuarial median survival and disease free survival (DFS) were 14.4 and 10.7 mths, respectively. The PCNA-values ranged from 3.2 to 70% (median 9%), there were 7 aneuploid and 13 euploid tumors. SFP in the euploid tumors ranged from 4 to 14.5% (median 10.5%). Neither SFP nor ploidy had a significant influence on the outcome. The patients were divided according to their PCNA-value in higher (n=10) and lower (n=10) than the median. The survival and DFS were 13.1 and 7.6 mths for the group > 9% and both values were greater than 15 mths for the group <9%. The difference in DFS was significant (p = 0.03, log rank test). Conclusion: These results fall in line with other studies showing the influence of the pretherapeutic proliferation on the outcome after radiotherapy. However, there are several points to mention. This study was performed during a clinical trial of the efficacy of a moderately accelerated therapy regimen. This therapy certainly reduces the influence of the proliferation on the outcome, but as our results show, the patients with faster proliferating tumors still have a worse outcome. They have a shorter survival and DFS. The DFS, i.e. the time until progression, is the more relevant parameter in this study, because of various salvage therapies, which may influence overall survival. However, it is unlikely that one single parameter, in this case proliferation, will adequately predict the response to radiotherapy, although our patients represent a clinically homogeneous sample and received identical therapy.}
doi = {10.1016/0360-3016(95)97878-5}
journal = []
issue = {971}
volume = {32}
journal type = {AC}
place = {United States}
year = {1995}
month = {Jul}
}