Does the method of primary treatment affect the pattern of first recurrence in high-grade serous ovarian cancer?

Himoto, Yuki; Cybulska, Paulina; Shitano, Fuki; Sala, Evis; Zheng, Junting; Capanu, Marinela; Nougaret, Stéphanie; Nikolovski, Ines; Vargas, Hebert Alberto; Wang, Wei; Mueller, Jennifer J.; Dennis, S.; Lakhman, Yulia

doi:10.1016/j.ygyno.2019.08.011

Cited by 17 publications

(14 citation statements)

References 44 publications

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“…Thus, NACT may increase the risk of leaving small tumor colonies and the rate of complete debulking may be overestimated. This hypothesis is supported by the results of a recent study by Himoto et al, which revealed that patients treated with NACT-IDS were more likely to experience recurrence in the same sites as the original disease, whereas patients who underwent PDS had higher number of recurrences in new locations; away from the surgically cleared sites (25). In line with this, two other studies have shown that large tumor burdens impair chemotherapy response (26,27).…”

Section: Discussionmentioning

confidence: 55%

Neoadjuvant Chemotherapy Reduces the Treatment-free Interval After First-line Treatment in Patients With Advanced Ovarian Cancer

et al. 2020

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Background/Aim: The aim of the study was to compare platinum resistance and treatment-free interval (TFI) following treatment with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) or primary debulking surgery (PDS) in women with advanced epithelial ovarian cancer (EOC). Patients and Methods: The study included patients diagnosed with primary EOC, stage IIIC or IV, between 2005 and. Patients were grouped according to first-line treatment (PDS vs. NACT-IDS). Date of second-line treatment initiation was used to evaluate platinum sensitivity. Results: The study population included 521 patients, of which 371 (71%) and 150 (29%) underwent PDS and NACT-IDS, respectively. We found no difference in platinum resistance between groups. Platinum-sensitive patients treated with NACT-IDS had a shorter median TFI (372 vs. 497 days, p=0.042). Similarly, patients with no residual tumor after IDS had a shorter median TFI (280 vs. 302 days, p=0.005). Conclusion: NACT-IDS may shorten the TFI after first-line platinum-based chemotherapy.Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies (1, 2). Most women are diagnosed in advanced stages (The International Federation of Gynecology and Obstetrics (FIGO) stage III-IV), for which the prognosis is poor (3). The traditional treatment for EOC is primary debulking surgery (PDS) followed by adjuvant platinum-based chemotherapy (4). However, in the last decade, the use of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) has increased (5, 6).For PDS, complete tumor resection has a profoundly positive impact on survival (7, 8). However, while randomized controlled trials comparing PDS to NACT-IDS demonstrated superior surgical outcomes for NACT-IDS, this finding did not translate into better survival (9, 10). Another important factor regarding survival is platinum sensitivity to first-line chemotherapy since platinumresistant disease is associated with poor prognosis (4,(11)(12)(13). The potential risk of developing platinum resistance rises with increasing tumor burden (14). Accordingly, patients treated with chemotherapy before debulking surgery may be more susceptible to developing resistance to chemotherapy.Hypothetically, the reason why the superior surgical outcomes of NACT-IDS do not translate into better survival could in part be explained by a greater likelihood of developing platinum resistance when treated with NACT-IDS than when treated with PDS. Thus, the present study compared platinum resistance and treatment-free interval (TFI) after first-line treatment with PDS or NACT-IDS. Patients and MethodsStudy population. This study included patients treated at Copenhagen University Hospitals, Rigshospitalet or Herlev Hospital, and identified in the Danish Gynecological Cancer Database (DGCD) (15) between January 2005 and May 2013 with primary epithelial stage IIIC or IV cancer in the ovaries, fallopian tubes, or peritoneum. We selected two university hospitals from the greater Copenhagen region...

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Section: Discussionmentioning

confidence: 55%

Neoadjuvant Chemotherapy Reduces the Treatment-free Interval After First-line Treatment in Patients With Advanced Ovarian Cancer

et al. 2020

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“…Thus, generation of the CP70 drug resistant cell line closely mimics clinical patient treatment protocols. 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].…”

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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“…In addition, patients treated with NACT-IDS suffer from recurrence more often than patients treated with PDS 26 . In our study, during the follow-up period, 14 (56.00%) patients experienced recurrence in the NACT group, and 8 (36.36%) had recurrence in the PDS group; the difference was not significant (P 0.05).…”

Section: Discussionmentioning

confidence: 99%

Advanced stage ovarian cancer patients with neoadjuvant chemotherapy suffered worse recurrence free survival

Zhou

Feng

et al. 2020

Preprint

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Background Neoadjuvant chemotherapy (NACT) has been applied for the treatment of patients with advanced-stage epithelial ovarian cancer (EOC), fallopian tube cancer, and primary peritoneal cancer, as these patients have a low likelihood of achieving optimal debulking and are thus poor surgical candidates. Herein, we explore the effects of NACT and compare the surgical outcomes and recurrence data in patients who receive interval debulking surgery followed NACT(NACT-IDS) or primary debulking surgery(PDS). Methods A retrospective, single-center, observational study was conducted. Patients with advanced-stage EOC, fallopian tube cancer and primary peritoneal cancer who were treated with NACT or primary debulking surgery were enrolled. The effects of NACT as well as the surgical outcomes and recurrence data were compared between the NACT-IDS and PDS groups. Results The albumin level was elevated (42.61±3.46 g/L vs. 37.47±5.42 g/L, P=0.001) and the levels of CA12-5 and HE4 significantly decreased (P=0.002, 0.003) in patients after neoadjuvant courses. The operation time, amount of blood loss during surgery, rate of bowel resection, time to chemotherapy, and platinum-free interval were comparable between the two groups (P＞0.05). Recurrence-free survival was worse in the NACT-IDS group than in the PDS group (HR=2.406, 95% CI[1.024, 5.657]). Conclusion NACT improved the condition of advanced-stage patients, but a poor recurrence free survival rate was observed; thus, NACT should not be applied in non-selected patients.

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Does the method of primary treatment affect the pattern of first recurrence in high-grade serous ovarian cancer?

Cited by 17 publications

References 44 publications

Neoadjuvant Chemotherapy Reduces the Treatment-free Interval After First-line Treatment in Patients With Advanced Ovarian Cancer

Neoadjuvant Chemotherapy Reduces the Treatment-free Interval After First-line Treatment in Patients With Advanced Ovarian Cancer

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

Advanced stage ovarian cancer patients with neoadjuvant chemotherapy suffered worse recurrence free survival

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