The shift toward neo‐adjuvant chemotherapy and interval debulking surgery for management of advanced ovarian and related cancers in a population‐based setting: Impact on clinical outcomes

Nicklin, James L.; McGrath, Shaun; Tripcony, Lee; Garrett, Andrea; Land, Russell; Perrin, Lewis; Chetty, Naven; Jagasia, Nisha; Crandon, Alex J.; Nascimento, Marcelo; Walker, Graeme E.; Sanday, Karen; Obermair, Andreas

doi:10.1111/ajo.12665

Cited by 19 publications

(17 citation statements)

References 13 publications

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“…Following the implementation of cytoreductive surgery and adjuvant chemotherapy, the 5-year survival rate of patients with OC has increased to ~50%; however, this improvement does not match the rates for thyroid or prostate cancer ( 5 , 24 ). Advanced stage, poor tumor differentiation and large tumor size are suggested to be associated with poor prognosis in patients with OC, and other pathological data, including the increased expression of cleaved caspase-3 and the PD-L1 in OC, have also been identified as predictive factors for OC prognosis ( 4 , 25 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

Expression of V‑domain immunoglobulin suppressor of T cell activation is associated with the advanced stage and presence of lymph node metastasis in ovarian cancer

et al. 2018

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V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel negative immune checkpoint that belongs to the B7 family. VISTA is primarily expressed on hematopoietic cells and inhibits T cell proliferation and cytokine production. The blockade of VISTA has demonstrated promising results in certain murine tumor models. In the present study, an immunohistochemical analysis of VISTA expression on tumor cells, intratumoral immune cells and vascular endothelial cells was performed in a cohort of 65 patients with ovarian cancer (OC). The associations between VISTA expression and different clinicopathological characteristics were evaluated using Fisher's exact test, and the analysis of overall survival in different groups was performed by the construction of Kaplan-Meier curves. The results indicated that high expression of VISTA on tumor cells or ICs was significantly associated with advanced tumor stage and the presence of lymph node metastasis (LNM). However, the percentage of cases with high expression of VISTA on tumor cells (24.6%) was decreased compared with those with high expression on ICs (44.6%). There was no association between VISTA expression and the 5-year overall survival rate, and advanced-stage disease was the only independent predictor of poor prognosis based on multivariate Cox regression analysis. In general, VISTA expression increased with advanced disease stage and LNM, indicating that VISTA expression is involved in the progression of OC. More importantly, these data implicate VISTA as a candidate immunotherapeutic target in OC.

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Section: Discussionmentioning

confidence: 99%

Expression of V‑domain immunoglobulin suppressor of T cell activation is associated with the advanced stage and presence of lymph node metastasis in ovarian cancer

et al. 2018

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“…Although complete primary debulking has been associated with higher survival in late-stage patients, 16 a lack of consensus still exists, with an Australian retrospective study finding that an increasing shift towards interval debulking was associated with increased survival. 17 Commentators argue that primary debulking should still be considered the treatment of choice for fit patients with advanced resectable disease, whereas interval debulking is more suitable for patients with poorer performance and nutritional status, who are more likely to develop post-operative morbidity and mortality. 18 Furthermore, most guidelines did not explicitly recommend extensive/ultra-radica' surgery and yet clinicians from higher performing countries were more likely than those from lower performing countries to agree with 'ultra-radical' surgery.…”

Section: Surgerymentioning

confidence: 99%

Exploring international differences in ovarian cancer treatment: a comparison of clinical practice guidelines and patterns of care

Norell

Butler

Farrell

et al. 2020

Int J Gynecol Cancer

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IntroductionThe International Cancer Benchmarking Partnership demonstrated international differences in ovarian cancer survival, particularly for women aged 65–74 with advanced disease. These findings suggest differences in treatment could be contributing to survival disparities.ObjectiveTo compare clinical practice guidelines and patterns of care across seven high-income countries.MethodsA comparison of guidelines was performed and validated by a clinical working group. To explore clinical practice, a patterns of care survey was developed. A questionnaire regarding management and potential health system-related barriers to providing treatment was emailed to gynecological specialists. Guideline and survey results were crudely compared with 3-year survival by ‘distant’ stage using Spearman’s rho.ResultsTwenty-seven guidelines were compared, and 119 clinicians completed the survey. Guideline-related measures varied between countries but did not correlate with survival internationally. Guidelines were consistent for surgical recommendations of either primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery with the aim of complete cytoreduction. Reported patterns of surgical care varied internationally, including for rates of primary versus interval debulking, extensive/‘ultra-radical’ surgery, and perceived barriers to optimal cytoreduction. Comparison showed that willingness to undertake extensive surgery correlated with survival across countries (rs=0.94, p=0.017). For systemic/radiation therapies, guideline differences were more pronounced, particularly for bevacizumab and PARP (poly (ADP-ribose) polymerase) inhibitors. Reported health system-related barriers also varied internationally and included a lack of adequate hospital staffing and treatment monitoring via local and national audits.DiscussionFindings suggest international variations in ovarian cancer treatment. Characteristics relating to countries with higher stage-specific survival included higher reported rates of primary surgery; willingness to undertake extensive/ultra-radical procedures; greater access to high-cost drugs; and auditing.

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“…The current standard treatment strategy for advanced epithelial ovarian cancer (AEOC) is primary cytoreductive surgery in combination with platinum-based first-line chemotherapy and radiotherapy or endocrine therapy ( 23 , 24 ). When adequate evaluation suggests that patients are less likely to receive a satisfactory outcome from tumor cell depletion surgery, neoadjuvant chemotherapy (NACT) followed by interval-based nodulation (NACT-IDS) after three platinum-based chemotherapy cycles has become an increasingly common treatment strategy ( 25 – 28 ). Overall, research has shown that the survival rate of patients with stage III or IV OC treated with NACT-IDS is not inferior to that of patients receiving primary cytoreductive surgery followed by chemotherapy ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Cross‑validation of genes potentially associated with neoadjuvant chemotherapy and platinum‑based chemoresistance in epithelial ovarian carcinoma

et al. 2020

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Ovarian carcinomas have the poorest prognosis and the highest mortality among gynecological malignancies. Neoadjuvant chemotherapy (NACT) is considered as a novel therapeutic strategy and an alternative treatment for advanced epithelial ovarian cancer (AEOC). The aim of the present study was to identify the core genes related to platinum-based NACT resistance in AEOC and to allow screening at the molecular level for the most appropriate ovarian cancer patients for NACT. We obtained three drug-resistant microarrays GSE114206, GSE41499 and GSE33482 from the Gene Expression Omnibus (GEO) database as well as a microarray representing NACT, GSE109934. Bioinformatics analysis revealed the nature of the four potential candidate genes for using in functional enrichment analyses and interaction network construction. The potential associations and possible genetic alterations among the DEGs were summarized using the STRING database in Cytoscape and the cBioPortal visualization tool, respectively. A total of 63 genes were identified as DEGs from GSE109934 representing NACT. From the drug-resistant GSE114206 and GSE41499 datasets, 106 DEGs containing 36 upregulated genes and 70 downregulated genes were selected, and from the drug-resistant GSE114206 and GSE33482 datasets, 406 DEGs with 157 upregulated genes and 249 downregulated genes were selected. The 36 upregulated DEGs and the 70 downregulated genes were notably abundant in the different categories. In KEGG pathway analysis, the 157 upregulated genes and the 249 downregulated genes were concentrated in distinctive signaling pathways. Four potential genes associated with NACT and platinum-based chemoresistance were screened, including nuclear factor of activated T-cells, cytoplasmic 1 (NAFTc1), Kruppel-like factor 4 (KLF4), nuclear receptor subfamily 4 group A member 3 (NR4A3) and hepatocyte growth factor (HGF). Our study showed that the mRNA expression levels of NAFTc1, NR4A3 and HGF were increased in drug-resistant OC cell lines (all P<0.01), whereas the mRNA expression levels of KLF4 were notably lower in the SKOV3-CDDP and HeyA8-CDDP cell line (all P<0.01) but higher in the A2780-CBP cell line. The NAFTc1, KLF4, NR4A3 and HGF genes may be potential therapeutic targets for NACT and platinum-based chemoresistance factors as well as candidate biomarkers in AEOC. Determination of the expression levels of these four genes in tumor tissues before planning NACT treatment or initial surgery would be beneficial for AEOC patients.

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The shift toward neo‐adjuvant chemotherapy and interval debulking surgery for management of advanced ovarian and related cancers in a population‐based setting: Impact on clinical outcomes

Abstract: The increasing utilisation of NACT - IDS in the setting of a large centralised clinical service has been associated with increasing rates of optimal cytoreduction and survival rates have continued to rise in excess of those achieved in the trials reported to date.

Cited by 19 publications

References 13 publications

Expression of V‑domain immunoglobulin suppressor of T cell activation is associated with the advanced stage and presence of lymph node metastasis in ovarian cancer

Expression of V‑domain immunoglobulin suppressor of T cell activation is associated with the advanced stage and presence of lymph node metastasis in ovarian cancer

Exploring international differences in ovarian cancer treatment: a comparison of clinical practice guidelines and patterns of care

Cross‑validation of genes potentially associated with neoadjuvant chemotherapy and platinum‑based chemoresistance in epithelial ovarian carcinoma

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