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1.
Int J Mol Sci ; 24(13)2023 Jun 22.
Article in English | MEDLINE | ID: mdl-37445679

ABSTRACT

Assessment of homologous recombination deficiency (HRD) status is now essential for ovarian cancer patient management. The aim of our study was to analyze the influence of ethnic variations, tumor purity, and neoadjuvant chemotherapy (CT) on the determination of HRD scores as well as to evaluate feasibility of HRD testing with the Amoy HRD Focus Assay in routine clinical practice. The HRD status, including the BRCA status and genomic scar score (GSS), was analyzed in 452 ovarian cancer specimens. The successful rate of HRD testing was 86% (388/452). The BRCA mutational rate was 29% (114/388); 252 samples (65%) were classified as HRD-positive. Our data demonstrate the feasibility of internal HRD testing by the AmoyDx HRD Focus Panel for high-grade serous ovarian cancer (HGSOC), showing results similar to other methods. The HRD rate in the Russian population is very similar to those of other European populations, as is the BRCA mutation frequency. The most substantial contribution to HRD level diversity is testing criteria depending on intrahospital arrangements. The analysis shows that biallelic BRCA alterations had higher GSS compared with those with monoallelic inactivation, consistent with positive HRD status. The study indicates that grades 1-2 of the pathological response caused by chemotherapy affect HRD scores and suggests controlling for tumor purity of 40% or more as a critical factor for GSS measurement.


Subject(s)
BRCA1 Protein , Ovarian Neoplasms , Female , Humans , Mutation , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/genetics , Ovarian Neoplasms/drug therapy , Russia , Homologous Recombination
2.
Int J Gynecol Cancer ; 22(9): 1597-603, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23051962

ABSTRACT

INTRODUCTION: Recurrence originating from the pelvic lymph node containing fibro-fatty tissue has consistently been identified as the most frequent pattern of treatment failure in early-stage cervical cancer. A surgical technique for the complete removal of the connective tissue content of the pelvis was introduced at St. Stephen Hospital in 1993 to improve oncological outcome by reducing the risk of recurrence from the pelvis. Efficacy and toxicity of the procedure were studied in 563 patients with stage IB cervical cancer with a completed 5-year follow-up. METHODS: Final pathology in 492 (87.4%) of 563 consecutive completed radical hysterectomies suggested that all tissue, which could contain tumor dissemination, was removed from the pelvis; thus, no adjuvant treatment was applied. Adjuvant chemoradiotherapy was advised in 71 cases (12.6%), where pathologic finding alluded tumor spread beyond the study criteria. FINDING: At completed 5-year follow-up, the overall survival of 492 patients who had surgery without adjuvant therapy was 94.0%. Pathologic stage, lymphovascular space involvement, pelvic lymph node metastases, histology classification, and grade had no significant influence on prognosis. The only factor that influenced the overall survival was International Federation of Gynecology and Obstetrics stage (IB1 or IB2). Five-year overall survival of 71 patients to whom adjuvant therapy was recommended was 56.3%. Five-year overall survival of the whole cohort (n = 563) was 88.8%. The complication rate did not seem to be different from the published data on traditional radical surgery in cervical cancer. CONCLUSIONS: Our results (in accordance with other recent publications) suggest that complete excision of the connective tissue content of the pelvis provides equal or better survival chances without any adjuvant treatment for almost 90% of operable patients with stage IB cervical cancer than less radical surgery with or without adjuvant treatment. We suggest this strategy to be mentioned as one alternative in future treatment protocols.


Subject(s)
Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Hysterectomy/methods , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgery , Adult , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/mortality , Cohort Studies , Disease Progression , Female , Humans , Hysterectomy/adverse effects , Hysterectomy/statistics & numerical data , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Survival Analysis , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/mortality , Young Adult
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