Evaluation of serial serum IL-6 levels in women with newly diagnosed ovarian cancer on a prospective clinical trial

5065 Background: Elevated levels of IL-6 in serum have been reported in patients (pts) with mullerian malignancies (MM) and have been associated with a poor prognosis. Little is know about the behavior of IL-6 during effective cytotoxic therapy and its correlation to various clinical parameters. Methods: Pts with surgically debulked FIGO Stage II, III, and IV MM were enrolled in the Modified Triple Doublets trial. 83 pts were assigned to a cohort in accordance with the extent of surgical debulking. Cohort I included women who had been optimally cytoreduced to <1cm of residual tumor. Cohort II consisted of pts who had either post-debulking residual disease >1cm or stage IV disease. Both cohorts were treated with 3 sequential chemotherapy doublets, gemcitabine/carboplatin, paclitaxel/carboplatin, and adriamycin/topotecan. Each doublet was delivered for 3 cycles. Serum was collected from pts prior to initiating each doublet at cycles 1, 4, 7 and at the end of study (post cycle 9). Serum IL-6 levels were measured in triplicate by sandwich ELISA. Results: Pts with MM had elevated levels of IL-6 following debulking surgery (mean = 12.7 pg/ml) as compared to normal controls (n = 11, mean IL-6 = 1.5 pg/ml, p =.01). While there was no significant correlation between IL-6 levels and stage of disease, the IL-6 serum concentrations did correlate with extent of surgical debulking (p = 0.0182). IL-6 concentrations dropped throughout all cycles of platinum based treatment with post platinum treatment mean concentration of 3.9pg/ml. IL-6 levels did not correlate with outcome of second look operation and there was no statistically significant correlation between IL-6 and CA-125 levels (p = 0.1612). Survival data is still immature with a median follow-up of 34 months, yet elevation of IL-6 levels following surgery demonstrates a trend towards inferior survival. Conclusions: IL-6 levels are elevated in ovarian cancer pts following surgical debulking and correlate with the volume of residual disease following surgical cytoreduction. Values decrease during cytoreductive platinum based chemotherapy although IL-6 was not as predictive of response as was CA-125. Data demonstrates a weak correlation betweenworse survival and elevated IL-6 levels. Supported by the Lana Vento Foundation. No significant financial relationships to disclose.

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Progression-free survival (PFS) and second PFS (PFS2) by disease stage in patients (pts) with homologous recombination deficiency (HRD)-positive newly diagnosed advanced ovarian cancer receiving bevacizumab (bev) with olaparib/placebo maintenance in the phase III PAOLA-1/ENGOT-ov25 trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.5514 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 5514-5514

Author(s):

Patricia Pautier ◽

Philipp Harter ◽

Carmela Pisano ◽

Claire Cropet ◽

Susana Hernando Polo ◽

...

Keyword(s):

Ovarian Cancer ◽

Residual Disease ◽

Stage Iv ◽

Figo Stage ◽

Phase Iii ◽

Stage Iii ◽

Disease Stage ◽

Newly Diagnosed ◽

Platinum Based Chemotherapy ◽

Interval Surgery

5514 Background: In the Phase III PAOLA-1/ENGOT-ov25 trial (NCT02477644), the addition of maintenance olaparib to bev in pts with newly diagnosed advanced high-grade ovarian cancer (HGOC) resulted in a significant PFS benefit, particularly in HRD-positive (HRD+) pts (hazard ratio [HR] 0.33; 95% CI 0.25–0.45) (Ray-Coquard et al. NEJM 2019). We explored efficacy in HRD+ pts by disease stage. Methods: Pts with newly diagnosed, FIGO stage III–IV HGOC in response after platinum-based chemotherapy + bev received bev (15 mg/kg q3w for 15 months [mo]) + either olaparib (300 mg bid for 24 mo) or placebo (pbo). This exploratory analysis evaluated PFS (data cut-off [DCO]: Mar 22 2019) and PFS2 (DCO: Mar 22 2020) in HRD+ pts (tumor BRCA1/ BRCA2 mutation [tBRCAm] or genomic instability score [Myriad myChoice HRD Plus] ≥42) by FIGO stage. Results: 387/806 randomized pts (48%) were HRD+; 272/387 (70%) had stage III disease and 115/387 (30%) had stage IV disease. 153 (56%) HRD+ stage III pts and 61 (53%) HRD+ stage IV pts had a tBRCAm. Among HRD+ stage III pts, 172 (63%) had upfront surgery (51/172 [30%] had residual disease) and 90 (33%) had interval surgery (19/90 [21%] had residual disease); 52 (45%) HRD+ stage IV pts had upfront surgery (34/52 [65%] had residual disease) and 55 (48%) had interval surgery (18/55 [33%] had residual disease). Median follow-up for PFS and PFS2 was respectively 24.8 and 37.2 mo in HRD+ stage III pts and 24.0 and 37.0 mo in HRD+ stage IV pts. Median PFS, PFS2 and HRs are in the Table. Among HRD+ stage III pts, 36-mo PFS2 (olaparib + bev vs pbo + bev) was 74% vs 60%; among HRD+ stage IV pts, 53% vs 30%. Among HRD+ stage III pts with no residual disease after upfront surgery, HR (95% CI) for PFS was 0.15 (0.07–0.30) and for PFS2 was 0.22 (0.06–0.67). Among HRD+ stage III pts with residual disease after upfront surgery or who received neoadjuvant chemotherapy, or HRD+ stage IV pts, HR (95% CI) for PFS was 0.38 (0.27–0.53) and PFS2 was 0.68 (0.46–1.03). Conclusions: In the PAOLA-1 study, maintenance olaparib + bev provided a PFS and PFS2 benefit over pbo + bev in HRD+ pts, irrespective of FIGO stage and residual disease after upfront surgery. Clinical trial information: NCT02477644. [Table: see text]

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Role of discoidin domain receptor 2 (DDR2) and microRNA-182 in survival of women with high-grade serous ovarian cancer

Tumor Biology ◽

10.1177/1010428318823988 ◽

2019 ◽

Vol 41 (1) ◽

pp. 101042831882398

Author(s):

Susana Ramalho ◽

Liliana AL De Angelo Andrade ◽

Cássio Cardoso Filho ◽

Rodrigo de Andrade Natal ◽

Marina Pavanello ◽

...

Keyword(s):

Ovarian Cancer ◽

Residual Disease ◽

Figo Stage ◽

Stage I ◽

High Grade ◽

Serous Ovarian Cancer ◽

Discoidin Domain Receptor ◽

Post Surgery ◽

Platinum Based Chemotherapy ◽

Discoidin Domain Receptor 2

The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (DDR2) and miR-182 expression with response to platinum-based chemotherapy and survival in women with high-grade serous ovarian cancer (HGSOC). We evaluated 78 women with HGSOC stages I-IV, diagnosed between 1996 and 2013, and followed up until 2016. DDR2 expression was assessed using immunohistochemistry on tissue microarray slides. The microRNAs were evaluated by qRT-PCR. DDR2 expression was high in 11 (14.1%) women. PFS was significantly lower in women with FIGO stage I/II – versus III/IV, post-surgery residual disease and high expression of DDR2. Women with postsurgery residual disease, FIGO stage I/II – versus III/IV and DDR2 expression had worse OS, but only post-surgery residual disease remained an independent prognostic factor for worse OS in multivariable analysis. miR-182 expression levels were significantly lower in patients harboring tumors with higher expression of DDR2 (p < 0.001). In this relatively large cohort of women with HSGOC, higher DDR2 expression was associated with lower miR-182 levels and worse PFS, suggesting that these molecules may be associated with mechanisms of HGSOC progression.

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Endometrioid Carcinoma of the Ovary: A Retrospective Analysis of 106 Cases

Tumori Journal ◽

10.1177/030089169808400508 ◽

1998 ◽

Vol 84 (5) ◽

pp. 552-557 ◽

Cited By ~ 16

Author(s):

Giuseppe Grosso ◽

Francesco Raspagliesi ◽

Gabriela Baiocchi ◽

Emanuela Di Re ◽

Maria Colavita ◽

...

Keyword(s):

Residual Disease ◽

Univariate Analysis ◽

Stage Iv ◽

Tumor Grade ◽

Residual Tumor ◽

Figo Stage ◽

Lymph Node Status ◽

Endometrioid Carcinoma ◽

Synchronous Tumors ◽

Carcinoma Of The Ovary

Aims and background This report retrospectively analyzes 106 cases of endometrioid carcinoma of the ovary treated at the National Cancer Institute of Milan from 1974 through December 1993. In 12 of the 106 cases (11.3%) a synchronous carcinoma of the uterine body was observed. Methods and study design Only patients who had previously untreated disease were included in the study. Patients with synchronous tumors were staged according to their ovarian cancer and treated according to the stage of that disease. Results Thirty-nine patients (36.8%) had stage I, 17 (16.0%) stage II, 43 (40.6%) stage III, and 7 (6.6%) stage IV disease. Moderately plus poorly differentiated tumors were present in 76 of the 106 cases (71.7%). Considering the 67 patients with advanced disease, residual tumor was absent in 27 cases (40.3%), ≤ 2 cm in 17 (25.4%), and > 2 cm in 23 (34.3%) cases. Systematic pelvic and para-aortic lymphadenectomy was performed in 60 patients (56.6%); selective sampling was carried out in 23 cases (21.7%). After surgery, 77 patients underwent various chemotherapy regimens. Conclusion Using univariate analysis, FIGO stage, tumor grade, residual disease after surgery, lymph node status, and platinum in the chemotherapy regimen significantly influenced 5-year survival. However, when all these variables were included in a multivariate analysis only FIGO stage still had a significant impact on survival. Survival analysis also showed a trend towards longer survival in patients with synchronous tumors.

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Chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer: Results from the MRC CHORUS trial.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5500 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5500-5500 ◽

Cited By ~ 34

Author(s):

Sean Kehoe ◽

Jane Hook ◽

Matthew Nankivell ◽

Gordon C. Jayson ◽

Henry Charles Kitchener ◽

...

Keyword(s):

Ovarian Cancer ◽

Controlled Trial ◽

Advanced Ovarian Cancer ◽

Pelvic Mass ◽

Stage Iv ◽

Figo Stage ◽

Phase Iii ◽

Initial Surgery ◽

Platinum Based Chemotherapy ◽

Optimal Debulking

5500 Background: First line treatment of advanced ovarian cancer (OC) is accepted to be primary surgery (PS) followed by adjuvant platinum-based chemotherapy (P-CT). However, the EORTC55971 trial suggested neoadjuvant chemotherapy (NACT) is an alternative, showing increased optimal debulking rates and reduced surgical complications without detriment to survival. CHORUS (CRUK 07/009) is the 2nd phase III randomized controlled trial to investigate timing of initial surgery in OC. Methods: Patients (pts) with clinical FIGO stage III-IV OC (pelvic mass, extrapelvic metastases and CA125/CEA ratio >25) were randomized to standard treatment (PS followed by 6 cycles P-CT) or NACT (3 cycles P-CT either side of surgery). CHORUS was designed to demonstrate non-inferiority of NACT, excluding a 6% absolute detriment in 3yr survival from 50% expected with PS (1-sided alpha 10%). Primary outcome was overall survival (OS) and secondary outcomes were progression free survival (PFS), toxicity and quality of life. Results: 550 women (276 PS, 274 NACT) were randomized from 74 centres (72 UK, 2 NZ) between Mar 2004 and Aug 2010. Baseline characteristics were well balanced: median age 65yrs, median tumor size 80mm, 25% FIGO stage IV, 19% WHO PS 2. Median follow-up was 3yrs, 410 pts have died. Treatment data are summarized in the Table. 3yr survival in the control arm was 32%. Intention to treat analysis showed a median OS of 22.8 months for PS vs 24.5 months for NACT (hazard ratio (HR) 0.87 in favor of NACT, 80% CI 0.76 – 0.98) and median PFS of 10.2 vs 11.7 months (HR 0.91, 0.81 – 1.02). OS results represent a 5% absolute benefit in 3yr survival for NACT to 37% and the upper 80% CI allows us to exclude a survival benefit for PS. Conclusions: NACT was associated with increased optimal debulking, less early mortality and similar survival in this poor prognosis group. CHORUS results are consistent with EORTC55971 and strengthen evidence that NACT is a viable alternative to PS. Clinical trial information: ISRCTN74802813. [Table: see text]

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Adoptive Cell Immunotherapy for Epithelial Ovarian Cancer

10.1093/med/9780190248208.003.0005 ◽

2018 ◽

Author(s):

Samir A. Farghaly

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Residual Disease ◽

Adoptive Cell Therapy ◽

Human Leukocyte ◽

Progression Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

Residual Tumor ◽

Disease Recurrence ◽

Platinum Based Chemotherapy

The standard management for epithelial ovarian cancer (EOC) is a combination of aggressive debulking surgery with residual tumor of less than 1 cm and platinum-based chemotherapy. However, a high percentage of patients experience disease recurrence. Extensive efforts to find new therapeutic options have been made, albeit cancer cells develop drug resistance and malignant progression occurs. Novel therapeutic strategies are needed to enhance progression-free survival and overall survival of patients with advanced EOC. Several preclinical and clinical studies investigated feasibility and efficacy of adoptive cell therapy (ACT) in EOC. The aim of this chapter is to present an overview of ACT in EOC, focusing on Human Leukocyte Antigen (HLA)-restricted tumor infiltrating lymphocytes and MHC-independent immune effectors such as natural killer and cytokine-induced killer. The available data suggest that ACT may provide the best outcome in patients with low tumor burden, minimal residual disease, or maintenance therapy. Further preclinical studies and clinical trials are needed.

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Clinical characterization of long term survivors (LTS) in ovarian cancer (OC): Results of a propensity score matched (PSM) analysis of the international prospective tumor bank for ovarian cancer (TOC Network).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e17063 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e17063-e17063

Author(s):

Elena Ioana Braicu ◽

Hannah Woopen ◽

Joanna Glajzer ◽

Oliver Hunsicker ◽

Linn Woelber ◽

...

Keyword(s):

Ovarian Cancer ◽

Nearest Neighbor ◽

Clonal Diversity ◽

Residual Tumor ◽

Figo Stage ◽

Control Group ◽

Tumor Spread ◽

Clinical Appearance ◽

Platinum Based Chemotherapy ◽

Upper Abdomen

e17063 Background: OC has the highest mortality rate amongst gynecological malignancies. Nevertheless a small fraction of OC patients will survive longer than 8 years. Aim of our study was to analyze differences in the clinical appearance and management of LTS versus “classical” OC patients. Methods: OC patients living longer than 8 years were identified within the TOC Network between 1998 and 2008, representing the LTS subgroup. PSM analysis was used to select comparable groups of LTS and OC patients who died within first 5 years (control group - CG). PSM was conducted using nearest neighbor caliper matching without replacement to match LTS and CG for age, FIGO and residual tumor mass. All calculations were performed with the R project for Statistical Computing (R-packages used: “MatchIt”). Results: A total of 347 OC patients with different histological subtypes were included in the current analysis, i.e. 173 LTS and 174 in the CG. After PSM 114 patients remained in each group. Patients had similar age, FIGO stage and residual mass (p = 0.99, p = 0.35 and p = 0.88, respectively). Tumor spread in middle and upper abdomen (p = 0.002 and 0.013, respectively) was higher and diaphragm, mesentery and peritoneum (p = 0.009, 0.037 and 0.002, respectively) were significantly more often involved in CG than in the LTS. When only considering the HGSOC patients, 95 patients remained in each group. All patients received surgery and platinum based chemotherapy. The PSM analysis showed significant higher involvement of upper abdomen (p = 0.028), higher peritoneal spread (p = 0.002), higher ascites volume (p = 0.0007) and higher bowel resection rates (p = 0.002) in the CG compared to LTS. Neoadjuvant chemotherapy rate was similar in the LTS and CG (p = 0.5). Conclusions: Based on this PSM analysis, HGSOC-LTS seem to have mainly similar clinical pattern as the control group, however with lower rates of ascites and involvement of upper abdomen. Molecular characterization including analysis of clonal diversity might help elucidate mechanisms of tumor spread and good prognosis.

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The Value of CA 125 and CA72-4 in Management of Patients with Epithelial Ovarian Cancer

Disease Markers ◽

10.1155/1998/738321 ◽

1998 ◽

Vol 14 (3) ◽

pp. 155-160 ◽

Cited By ~ 16

Author(s):

Salah T. Fayed ◽

Samira M. Ahmad ◽

Samar K. Kassim ◽

Ali Khalifa

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Residual Disease ◽

Ca 125 ◽

Platinum Based Chemotherapy ◽

Pelvic Masses ◽

Radiometric Assay ◽

Normal Women

The role of the tumor markers CA125 and CA72-4 has been evaluated in the diagnosis and management of ovarian cancer. Both markers were measured in 30 patients with proven epithelial ovarian cancer, 30 patients with benign pelvic masses and 30 normal women. CA125 and CA72-4 were measured using the luminometric immunoassay and immuno-radiometric assay respectively. All patients with ovarian cancer were submitted to surgical staging and cytoreduction followed by adjuvant platinum based chemotherapy for 3–6 courses. Fixing the specificity at 95%, CA125 had a sensitivity of 76.7% at a cut-off 85u/ml while CA72-4 had a sensitivity of 70% at a cut-off 8.5 u/ml. The combination of CA72-4 with CA125 increased the sensitivity to 95% while fixing the specificity at 95%. Among seven cases with stage I and II ovarian cancer five cases had CA125 level below 85 U/ml, three patients out of them had CA72-4 above 8.5 U/ml. CA 72-4 could reflect the residual disease following cytoreduction and could improve the detection of relapse by CA125.Conclusion: CA72-4 could complement the standard tumor marker CA125 both in diagnosis and follow up of patients with epithelial ovarian cancer.

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The clinical and pathological characteristics and survival of patients with advanced ovarian cancer

SCRIPTA MEDICA ◽

10.5937/scriptamed52-33897 ◽

2021 ◽

Vol 52 (3) ◽

pp. 205-210

Author(s):

Miroslav Popović ◽

Tanja Milić-Radić ◽

Arnela Cerić-Banićević

Keyword(s):

Ovarian Cancer ◽

Residual Disease ◽

Advanced Ovarian Cancer ◽

Figo Stage ◽

Ovarian Tumour ◽

Ca 125 ◽

Optimal Cytoreduction ◽

Chi Square ◽

Pathological Characteristics ◽

Significant Difference

Introduction: Ovarian cancer has the highest mortality rate of all gynaecologic malignancies. The aim of this study was the evaluation of the clinical pathological characteristics and survival analysis of primarily operated patients with advanced stages of malignant epithelial ovarian tumour. Methods: The research was conducted as a cohort study with 59 patients with FIGO stage III and IV, which were primarily operated between 1 January 2008 and 31 December 2010 (three years). Age, comorbidities, BMI, presence of ascites, the level of the marker CA-125, histopathology and FIGO stage were analysed. The survival rate was estimated at the level of 1, 3 and 5 years. Results: The median age was 53 years (range 29-86). The most common histopathological type was serous (66.1 %) and the most common FIGO stage was 3a (49.2 %). Optimal cytoreduction was performed in 35.5 % of patients, 84.7 % of patients survived for one year, 44.1 % three years and 37.3 % for five years. The median survival was 26.25 months (range 0-91). Chi-square test showed significant difference between the number of months of survival and: the value of CA125 (t = 2.004, p = 0.050), cytoreduction (p < 0.001) and FIGO stage (p < 0.01). Conclusion: According to the results of this study, optimal cytoreduction and FIGO stage significantly influence survival (p < 0.001). Optimal cytoreduction (< 2 cm of residual disease) had the highest prognostic value for survival. A total five-year survival in this study was 37.3 %.

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Pazopanib (Paz) monotherapy in Asian women who have not progressed after first-line chemotherapy for advanced ovarian, Fallopian tube, or primary peritoneal carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5512 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5512-5512 ◽

Cited By ~ 2

Author(s):

Rongyu Zang ◽

Lingying Wu ◽

Jianqing Zhu ◽

Beihua Kong ◽

Byoung-Gie Kim ◽

...

Keyword(s):

Ovarian Cancer ◽

Fallopian Tube ◽

Residual Disease ◽

Advanced Ovarian Cancer ◽

Figo Stage ◽

Small Sample ◽

Stage Ii ◽

Ca 125 ◽

Asian Women ◽

Debulking Surgery

5512 Background: Paz, an oral multikinase inhibitor of VEGF, PDGF and c-Kit has showed activity in advanced ovarian cancer. This study evaluated paz as maintenance therapy in Asian women with advanced ovarian cancer. Methods: Subjects with FIGO stage II, III, or IV ovarian, fallopian tube, or primary peritoneal cancer whose disease had not progressed after debulking surgery and followed by chemotherapy were randomized 1:1 to paz 800 mg once daily or placebo for up to 24 months. Primary endpoint was PFS by RECIST v1.0 based on visit date. If a progression occurred between the 2 scheduled visits (6 mos apart), progression was considered to have occurred at the next scheduled scan date. This minimized potential bias due to any imbalance of visit frequency between the arms. Results: 145 Asian subjects were randomized; 144 were treated. Mean age was 52.9 years. At diagnosis 17% were FIGO stage II, 73% stage III and 10% stage IV. After debulking surgery, 30% (n = 44) had no residual disease and 41% (n = 59) had. 47% (28/59) had residual disease ≤1cm. Prior to randomization, all subjects received median 8 cycles of chemotherapy; all subjects received platinum and taxane. At randomization 81% had ECOG status 0, 97% were disease free and all had normal CA-125. At clinical data cut-off median PFS was 18.1 months in both arms. Because of the small sample size a HR was not calculated but the KM curves indicated a trend in favor of paz from 6 to 18 mos; the curves crossed after 18 mos. The adverse event (AE) profile for paz was similar to previous reports except rates of hypertension and neutropenia were higher. The most frequent AEs (≥ 20%) on the paz arm were hypertension (76%), neutropenia (64%), leucopenia (53%), diarrhea (47%), hair color changes (40%), palm-plantar erythrodysaethesia syndrome (29%), ALT increase (28%), thrombocytopenia (24%), AST increase (22%) and TSH increase (21%). Most of these AEs were Grade 1-2. Conclusions: The results of this study alone cannot confirm the efficacy of paz maintenance treatment in Asian women with ovarian cancer, but should be interpreted in conjunction of AGO-OVAR16 study. Clinical trial information: NCT01227928.

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