scholarly journals Prognostic significance of supraclavicular lymphadenopathy in patients with high-grade serous ovarian cancer

2019 ◽  
Vol 29 (9) ◽  
pp. 1377-1380
Author(s):  
Paulina Cybulska ◽  
Sara A Hayes ◽  
Alexandra Spirtos ◽  
Michael J Rafizadeh ◽  
Olga T Filippova ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Progression Free Survival ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Debulking Surgery ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Supraclavicular Lymph Nodes ◽  
Interval Debulking Surgery

ObjectivesTo assess outcomes and patterns of recurrence in patients with high-grade serous ovarian/tubal/primary peritoneal cancers with radiographic supraclavicular lymphadenopathy at diagnosis.MethodsWe evaluated all patients with newly diagnosed high-grade serous ovarian cancers treated at our center between January 1, 2008 and May 1, 2013 who had supraclavicular lymphadenopathy (defined as ≥1 cm in short axis) on radiographic imaging (either computed tomography or positron emission tomography) at the time of diagnosis.ResultsOf 586 patients with high-grade serous ovarian cancer receiving primary treatment during the study period, we identified 13 (2.2%) with supraclavicular lymphadenopathy diagnosed on pre-treatment imaging. The median age at diagnosis was 52.0 years (range 38.2–72.3). Five (31%) had clinically palpable nodes on physical examination. Four (31%) had a known BRCA mutation. All 13 patients underwent neoadjuvant chemotherapy, followed by interval debulking surgery. Each patient received a median of four cycles of neoadjuvant intravenous chemotherapy (range 3–7). At interval debulking surgery, complete gross resection was achieved in nine (70%) patients, and optimal resection (0.1–1 cm residual disease) in four (30%). Eleven patients (85%) recurred; however, only one (8%) recurred in the supraclavicular lymph nodes. Median follow-up time was 44.3 months (range 22.4–95.0). Median progression-free survival for the cohort was 11.7 months (95% CI 9.2 to 14.1). Median overall survival was 44.3 months (95% CI 41.5 to 47.1). In patients obtaining complete gross resection at interval debulking surgery, median progression-free survival and overall survival were 13.9 months (95% CI 8.9 to 18.9) and 78.1 months (95% CI 11.1 to 145.1), respectively.ConclusionsIn our study, approximately 2% of patients with high-grade serous ovarian cancer presented with radiographic evidence of supraclavicular lymphadenopathy. Supraclavicular lymphadenopathy at diagnosis did not portend an unfavorable outcome when complete gross resection was achieved at interval debulking surgery.

scholarly journals Management of the Elderly Patients with High-Grade Serous Ovarian Cancer in the REAL-WORLD Setting

2021 ◽  
Vol 28 (2) ◽  
pp. 1143-1152
Author(s):  
Michalis Liontos ◽  
Alkistis Papatheodoridi ◽  
Angeliki Andrikopoulou ◽  
Nikolaos Thomakos ◽  
Dimitrios Haidopoulos ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Elderly Patients ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Optimal Treatment ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Debulking Surgery ◽  
Free Survival

Treatment of elderly patients with neoplasia is challenging. Age is a known prognostic factor in ovarian cancer but the optimal treatment of elderly patients has not been determined. We undertook a retrospective analysis to determine clinical practice in advanced-stage ovarian cancer patients older than 70 years of age. Methods: Medical records of women with high-grade serous ovarian cancer, stage III and IV were retrospectively analyzed. Results: A total of 735 patients were identified with a median age of 61.5 years. 22.4% among them were older than 70 years of age at diagnosis. First-line Progression-Free Survival (PFS) and Overall Survival (OS) were significantly worse in elderly patients in comparison to the younger ones [mPFS 11.3 months vs. 14.8 months, (p < 0.001) and mOS 30.2 months vs. 45.6 months (p < 0.001)]. However, elderly patients were characterized by worse ECOG-Performance Status and they were more frequently treated with Neoadjuvant Chemotherapy followed by Interval Debulking Surgery, while often they were more frequently denied debulking surgery compared to patients under 70 years of age. Moreover, elderly patients received more frequently monotherapy with platinum as frontline treatment. In contrast, there was no significant difference in the outcome of the debulking surgery in comparison to the younger patients or the frequency that gBRCA test was performed. Age over 70 years did not retain its significance for either Progression-Free Survival or Overall Survival when adjusted for all other reported prognostic factors. Conclusions: Elderly ovarian cancer patients have a worse prognosis. Comprehensive geriatric assessment should be performed for the optimal treatment of these patients.

Delays from neoadjuvant chemotherapy to interval debulking surgery and survival in ovarian cancer

2020 ◽  
Vol 30 (10) ◽  
pp. 1554-1561
Author(s):  
Ying L Liu ◽  
Qin C Zhou ◽  
Alexia Iasonos ◽  
Olga T Filippova ◽  
Dennis S Chi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Debulking Surgery ◽  
Free Survival ◽  
Interval Debulking Surgery ◽  
The Impact

IntroductionDelays from primary surgery to chemotherapy are associated with worse survival in ovarian cancer, however the impact of delays from neoadjuvant chemotherapy to interval debulking surgery is unknown. We sought to evaluate the association of delays from neoadjuvant chemotherapy to interval debulking with survival.MethodsPatients with a diagnosis of stage III/IV ovarian cancer receiving neoadjuvant chemotherapy from July 2015 to December 2017 were included in our analysis. Delays from neoadjuvant chemotherapy to interval debulking were defined as time from last preoperative carboplatin to interval debulking >6 weeks. Fisher’s exact/Wilcoxon rank sum tests were used to compare clinical characteristics. The Kaplan–Meier method, log-rank test, and multivariate Cox Proportional-Hazards models were used to estimate progression-free and overall survival and examine differences by delay groups, adjusting for covariates.ResultsOf the 224 women, 159 (71%) underwent interval debulking and 34 (21%) of these experienced delays from neoadjuvant chemotherapy to interval debulking. These women were older (median 68 vs 65 years, P=0.05) and received more preoperative chemotherapy cycles (median 6 vs 4, P=0.003). Delays from neoadjuvant chemotherapy to interval debulking were associated with worse overall survival (HR 2.4 95% CI 1.2 to 4.8, P=0.01), however survival was not significantly shortened after adjusting for age, stage, and complete gross resection, HR 1.66 95% CI 0.8 to 3.4, P=0.17. Delays from neoadjuvant chemotherapy to interval debulking were not associated with worse progression-free survival (HR 1.55 95% CI 0.97 to 2.5, P=0.062). Increase in number of preoperative cycles (P=0.005) and lack of complete gross resection (P<0.001) were the only variables predictive of worse progression-free survival.DiscussionDelays from neoadjuvant chemotherapy to interval debulking were not associated with worse overall survival after adjustment for age, stage, and complete gross resection.

Phase Ib with expansion study of olaparib plus weekly (Metronomic) carboplatin and paclitaxel in relapsed ovarian cancer patients

2019 ◽  
Vol 29 (2) ◽  
pp. 325-333 ◽  
Author(s):  
Saul Eugene Rivkin ◽  
James Moon ◽  
Desiree S Iriarte ◽  
Erik Bailey ◽  
Heather L Sloan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Complete Remission ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Free Survival ◽  
Phase Ib ◽  
Experienced Grade

ObjectiveOur goals were to: establish the maximum-tolerated dose of olaparib tablets combined with metronomic carboplatin and paclitaxel in patients with relapsed high-grade serous ovarian cancer; evaluate dose-limiting toxicities; and evaluate efficacy at the maximum tolerated dose.MethodsIn this open-label, single-arm, investigator-initiated trial (ClinicalTrials.gov NCT01650376), patients with high-grade serous ovarian cancer who failed primary platinum and taxane therapy received oral olaparib tablets twice daily days 1–3 each week combined with fixed-dose metronomic carboplatin AUC2 and paclitaxel 60 mg/m2 weekly for 3 out of 4 weeks. A 3 × 3 design was used to determine the olaparib maximum tolerated dose. Combination therapy continued until disease progression, but patients with partial or complete response were transitioned to olaparib maintenance therapy. All patients were included in the analysis.ResultsThe maximum tolerated dose of olaparib tablets was 150 mg twice daily with metronomic carboplatin and paclitaxel. 54 women were enrolled, 14 in phase Ib and 40 in the expansion phase. The median number of prior therapeutic regimens was 3. Response included 13 complete remission (24%) and 16 partial remission (30%) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) for an overall response rate of 54% (95% CI 40% to 67%). Of 47 patients who underwent BRCA testing, 23 were BRCA mutation (BRCAm) and 24 BRCA wild type (BRCAwt). Progression-free survival for BRCAm was 12.1 months versus 4.8 for BRCAwt (p=0.0001). Median overall survival for BRCAm was 24.1 months versus 10.4 months for BRCAwt (p=0.02). 42 patients (78%) experienced grade 3–4 toxicities with combination therapy; the most common were hematologic. There were no treatment related deaths. Among 14 patients who received maintenance therapy, 7 experienced grade 1–2 non-hematologic toxicities.ConclusionsOlaparib 150 mg tablet twice daily can be safely administered in combination with metronomic carboplatin and paclitaxel in pre-treated relapsed ovarian cancer with 24% complete remission. BRCAm patients had statistically significant longer progression-free survival and overall survival than BRCAwt.Trial registration numberNCT01650376.

scholarly journals Somatic Mutations in BRCA2 BRC Repeat Associated with Outcome in Patients with High Grade Serous Ovarian Cancer

2020 ◽  
Author(s):  
Guonan Zhang ◽  
Jie Zhang ◽  
Yi Zhu ◽  
Hong Liu ◽  
Yu Shi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Somatic Mutations ◽  
Progression Free Survival ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Blood Leukocytes ◽  
Free Survival ◽  
Chemotherapy Sensitivity ◽  
Factors Affecting ◽  
Platinum Based Chemotherapy

Abstract BackgroundThe interaction between BRCA2 BRC repeats and RAD51 is one of the great important factors affecting the homologous recombination in DNA damage repair of tumor cells. We investigated the effect of BRCA2 BRC repeat mutations on outcome in patients with high grade serous ovarian cancer (HGSOC) who received platinum-based chemotherapy.MethodsWe identified the type and location of BRCA2 BRC repeat mutations by PCR and DNA sequencing in tumor and peripheral blood leukocytes (PBL) samples of 113 patients with stage IIIC/IV high grade serous ovarian cancer (HGSOC), and assessed chemotherapy-free interval (CFI), progression-free survival (PFS) and overall survival (OS).Results24 (21.23%) cases with somatic mutation were identified in 113 HGSOC patients. Among them, 8 (7.1%) cases with nonsense mutation resulting in BRCA2 truncation significantly prolonged median CFI (37 vs 8 months,P=0.000), PFS (43 vs 14 months, p=0.000) and OS (56 vs 31 months, P=0.002); Interestingly, 16 (14.13%) cases with missense mutation also prolonged median CFI (15 vs 8 months, P=0.044), PFS (21 vs 14 months, P=0.049) and OS ( 38 vs 31 months, P=0.037). ConclusionsSomatic mutations in BRCA2 BRC5-8 repeat motifs are associated with platinum-based chemotherapy sensitivity and a better outcome in patients with HGSOC.

scholarly journals A Replication stress biomarker is associated with response to gemcitabine versus combined gemcitabine and ATR inhibitor therapy in ovarian cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Panagiotis A. Konstantinopoulos ◽  
Alexandre André B. A. da Costa ◽  
Doga Gulhan ◽  
Elizabeth K. Lee ◽  
Su-Chun Cheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Progression Free Survival ◽  
Replication Stress ◽  
Inhibitor Therapy ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Free Survival ◽  
Rb Pathway ◽  
Pathway Regulation ◽  
Stress Biomarker

AbstractIn a trial of patients with high grade serous ovarian cancer (HGSOC), addition of the ATR inhibitor berzosertib to gemcitabine improved progression free survival (PFS) compared to gemcitabine alone but biomarkers predictive of treatment are lacking. Here we report a candidate biomarker of response to gemcitabine versus combined gemcitabine and ATR inhibitor therapy in HGSOC ovarian cancer. Patients with replication stress (RS)-high tumors (n = 27), defined as harboring at least one genomic RS alteration related to loss of RB pathway regulation and/or oncogene-induced replication stress achieve significantly prolonged PFS (HR = 0.38, 90% CI, 0.17–0.86) on gemcitabine monotherapy compared to those with tumors without such alterations (defined as RS-low, n = 30). However, addition of berzosertib to gemcitabine benefits only patients with RS-low tumors (gemcitabine/berzosertib HR 0.34, 90% CI, 0.13–0.86) and not patients with RS-high tumors (HR 1.11, 90% CI, 0.47–2.62). Our findings support the notion that the exacerbation of RS by gemcitabine monotherapy is adequate for lethality in RS-high tumors. Conversely, for RS-low tumors addition of berzosertib-mediated ATR inhibition to gemcitabine is necessary for lethality to occur. Independent prospective validation of this biomarker is required.

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