Patterns of Recurrence and Clinical Outcome of Patients With Stage IIIC to Stage IV Epithelial Ovarian Cancer in Complete Response After Primary Debulking Surgery Plus Chemotherapy or Neoadjuvant Chemotherapy Followed by Interval Debulking Surgery: An Italian Multicenter Retrospective Study

Gadducci, Angiolo; Cosio, Stefania; Zizioli, Valentina; Notaro, Sara; Tana, Roberta; Panattoni, Andrea; Sartori, Enrico

doi:10.1097/igc.0000000000000843

Cited by 35 publications

(26 citation statements)

References 39 publications

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“…The included RCTs reported complete cytoreduction rates of 39–58% in NACT or 17–45% in PDS [ 7 , 8 , 12 ], which were overall lower than that seen in several retrospective studies [ 34 – 36 ]. Several factors influencing the complete cytoreduction rate are based on individual perceptions regarding disease status, age, performance status, and co-morbidities [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemotherapy versus primary debulking surgery in advanced epithelial ovarian cancer: A meta-analysis of peri-operative outcome

et al. 2017

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ObjectiveTo assess whether neoadjuvant chemotherapy (NACT) is superior to primary debulking surgery (PDS) with regard to optimal cytoreduction, peri-operative morbidity, mortality, and quality of life (QOL) in advanced epithelial ovarian cancer (EOC).MethodsWe searched the PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Registers of Clinical Trials for randomized controlled trials (RCTs) comparing NACT to PDS in women with Federation of International Gynaecologists and Obstetricians stage Ⅲ-Ⅳ EOC. RevMan 5.3 software was utilized for statistical analysis.ResultsFour RCTs involving 1,607 women with advanced EOC were included. Compared with PDS, NACT provided a higher rate of complete cytoreduction (risk ratio [RR], 1.95; 95% confidence interval [CI], 1.33 to 2.87), optimal cytoreduction (RR: 1.61 [95%CI: 1.05 to 2.47]), but there was no significant difference in residual disease 0–1 cm (p = 0.49). NACT was associated with lower peri-operative morbidity with respect to infection (RR: 0.30 [95% CI: 0.16 to 0.56]), gastrointestinal fistula (RR: 0.24 [95% CI: 0.06 to 0.95]), any grade 3 or 4 adverse event (RR: 0.29 [95% CI: 0.11 to 0.78]), and less post-surgical death within 28 days (RR: 0.14 [95% CI: 0.04 to 0.49]). NACT provided better QOL in terms of fatigue (weight mean difference [WMD], -3.28; [95% CI: -3.99 to -2.57]), role functioning (WMD: 5.29 [95% CI: 4.44 to 6.14]), emotional functioning (WMD: 6.19 [95% CI: 5.57 to 6.82]), and cognitive functioning (WMD: 1.02 [95% CI: 0.43 to 1.61]) at 6-month follow-up compared with PDS.ConclusionsNACT is associated with superior optimal cytoreduction, lower peri-operative morbidity as well as post-surgical mortality, and better QOL compared to initial surgery in patients with advanced EOC. Future research should focus on improving the efficacy of NACT.

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Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemotherapy versus primary debulking surgery in advanced epithelial ovarian cancer: A meta-analysis of peri-operative outcome

et al. 2017

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“…While this approach is necessary, clinical trials have repeatedly demonstrated that shortening the period of time between chemotherapy infusions provides a survival advantage [84, 85]. Moreover, recurrent disease is more prevalent in patients that are neo-adjuvant treated as opposed to those that receive up-front surgical de-bulking [86]. Importantly, one study shows that neo-adjuvant therapy increases the risk of platinum-resistant recurrent disease at late stage [87].…”

Section: Discussionmentioning

confidence: 99%

Tumor-infiltrating nerves create an electro-physiologically active microenvironment and contribute to treatment resistance

Kovács

Vermeer

Madeo

et al. 2020

Preprint

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Patients with densely innervated tumors do poorly as compared to those with sparsely innervated disease. Why some tumors heavily recruit nerves while others do not, remains unknown as does the functional contribution of tumor-infiltrating nerves to cancer. Moreover, while patients receive chemotherapeutic treatment, whether these drugs affect nerve recruitment has not been tested. Using a murine model of ovarian cancer, we show that tumor-infiltrating sensory nerves potentiate tumor growth, decrease survival, and contribute to treatment resistance. Furthermore, matched patient samples show significantly increased tumor innervation following chemotherapy. In vitro analysis of tumor-released extracellular vesicles (sEVs) shows they harbor neurite outgrowth activity. These data suggest that chemotherapy may alter sEV cargo, endowing it with robust nerve recruiting capacity.

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“…Residual post-surgery cancer cells have been considered a main origin of cancer recurrence, and some may even develop resistance to chemotherapy. [37][38][39] Recent studies have shown that chemo-resistant cancer cells are sensitive to the cytotoxic effect of CIK cells, 40,41 and thus, theoretically, CIK cells may be potent in eradicating residual tumor cells following surgery and chemotherapy. In this study, we showed that patients with residual tumor ≥ 1 cm yielded more favorable PFS rates from CIT.…”

Section: Discussionmentioning

confidence: 99%

Retrospective analysis of the efficacy of adjuvant CIK cell therapy in epithelial ovarian cancer patients who received postoperative chemotherapy

et al. 2018

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Cytokine-induced killer (CIK) cells are demonstrated to possess potent cytolytic effect against ovarian cancer cells in vitro and in vivo. However, the clinical efficacy of maintenance therapy of CIK cells in patients with epithelial ovarian cancer (EOC) after first-line treatment remains unclear. This retrospective study included 646 cases of postoperative EOC patients, 72 of which received chemotherapy and sequential immunotherapy (CIT group), and 574 of which received only chemotherapy (Control group). Patients in the CIT group received at least four cycles of CIK cell (range 8.0 × 109 – 1.3 × 1010 cells) transfusion, with the interval of each cycle being 2 weeks. Survival analysis showed a significantly higher overall survival (OS) rate in the CIT group compared with the control group, as well as a favorable progression-free survival (PFS). Univariate and multivariate analyses indicated that adjuvant CIT was an independent prognostic factor for the OS of patients with EOC. Furthermore, subgroup analyses showed that adjuvant CIT significantly improved the OS of patients older than 45 years, with CA125 ≤ 1000, or with moderate or poorly differentiated tumors, and prolonged the PFS of patients with residual disease > 1 cm. Additionally, Kaplan-Meier analyses revealed that a higher fraction of CD3+CD8+/CD3+CD56+ phenotypes or lower percentage of CD3+CD4+/CD3−CD56+ phenotypes in the infused CIK cells significantly associated with better survival of patients with EOC. Furthermore, across all processes of CIK cell immunotherapy in the CIT group, 12.5% (9/72) of patients developed self-limiting light fevers and shivering at grade 1 or 2. No immunotherapy-related serious reactions were recorded. These data indicate that adjuvant CIT with CIK cells is an effective therapeutic approach to prolonging the survival of EOC patients.

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Patterns of Recurrence and Clinical Outcome of Patients With Stage IIIC to Stage IV Epithelial Ovarian Cancer in Complete Response After Primary Debulking Surgery Plus Chemotherapy or Neoadjuvant Chemotherapy Followed by Interval Debulking Surgery: An Italian Multicenter Retrospective Study

Abstract: The clinical outcome of completely cytoreduced patients was significantly better for PDS group than for IDS group, and therefore, the achievement of no gross RD after surgery seemed to have a different prognostic relevance for the 2 groups.

Cited by 35 publications

References 39 publications

Neoadjuvant chemotherapy versus primary debulking surgery in advanced epithelial ovarian cancer: A meta-analysis of peri-operative outcome

Neoadjuvant chemotherapy versus primary debulking surgery in advanced epithelial ovarian cancer: A meta-analysis of peri-operative outcome

Tumor-infiltrating nerves create an electro-physiologically active microenvironment and contribute to treatment resistance

Retrospective analysis of the efficacy of adjuvant CIK cell therapy in epithelial ovarian cancer patients who received postoperative chemotherapy

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