Pattern of recurrence after interval cytoreductive surgery and HIPEC following neoadjuvant chemotherapy in primary advanced stage IIIC/IVA epithelial ovarian cancer

Sinukumar, Snita; Damodaran, Dileep; Ray, Mukurdipi; Mehta, Sanket; Paul, Lista; Bhatt, Aditi

doi:10.1016/j.ejso.2021.01.013

Cited by 10 publications

(7 citation statements)

References 25 publications

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“…For PM of digestive origin, it has been proposed that obstruction-free survival could be a useful end-point to demonstrate the benefit of HIPEC [74]. Our retrospective study showed that the visceral peritoneum was not a site of recurrence in 42% of the patients who developed recurrence/progression [34]. Thus, theoretically, TPP should not just prolong PFS but OS as well.…”

Section: Clinical End-points For Randomized Trials/prospective Studies Evaluating the Role Of Tppmentioning

confidence: 76%

“…When HIPEC was added to interval CRS, the incidence of intraperitoneal recurrence was significantly lower than that following CRS alone [33]. In another retrospective multi-center study of 97 patients undergoing interval CRS and HIPEC, systemic sites like the lung, liver and brain were the most common sites of recurrence [34].…”

Section: Patterns Of Recurrence In Patients With Advanced Epithelial Ovarian Cancermentioning

confidence: 97%

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Surgical and systemic therapies for addressing occult disease in advanced epithelial ovarian cancer

Bhatt¹,

Sinukumar²,

Kammar³

et al. 2022

Eur. J. Gynaecol. Oncol.

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The incidence of peritoneal recurrence in advanced epithelial ovarian cancer (EOC) is high and could be attributed to the high prevalence of occult disease the persists despite complete cytoreductive surgery (CRS) and systemic chemotherapy. Several therapeutic approaches have been used to address such occult disease. Hyperthermic intraperitoneal chemotherapy (HIPEC) acts on microscopic disease as well as free intraperitoneal cancer cells shed during surgery, thus, reducing the risk of recurrence. Maintenance therapies like Poly ADP-Ribosyl Polymerase (PARP) inhibitors and the anti-angiogenic agent bevacizumab are used as maintenance therapies to delay recurrence. The most definitive way to eradicate such occult disease completely is resection of the peritoneum. The high preponderance of occult disease in the parietal peritoneum and some regions of the visceral peritoneum has led some surgeons to investigate the role of a total parietal peritonectomy (TPP) performed along with wide resection of the visceral peritoneum as a strategy for addressing occult disease. The mechanism of action differs from that of HIPEC and systemic therapies. It is possible that the benefit of each of these therapies is additive. EOC is a heterogeneous disease with a number of clinicopathological and molecular factors influencing the prognosis. There are likely to be different subgroups of patients that benefit from each of these 4 therapies or a combination of these. In this manuscript, we review the rationale and current evidence for the use of each of these therapies and discuss the potential role of a TPP in light of other therapies.

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Section: Clinical End-points For Randomized Trials/prospective Studies Evaluating the Role Of Tppmentioning

confidence: 76%

Section: Patterns Of Recurrence In Patients With Advanced Epithelial Ovarian Cancermentioning

confidence: 97%

Surgical and systemic therapies for addressing occult disease in advanced epithelial ovarian cancer

Bhatt¹,

Sinukumar²,

Kammar³

et al. 2022

Eur. J. Gynaecol. Oncol.

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“…In advanced or recurrent ovarian cancer patients treated with cytoreductive surgery with HIPEC, the majority of patients experienced extra-peritoneal recurrences. Sinukumar et al (23) reported that systemic recurrences were common in advanced-stage ovarian cancer patient treated with IDS with HIPEC following NAC. These findings suggest that IDS with HIPEC may improve the intraperitoneal disease control within the abdomen due to the treatment of a hyperthermic cytotoxic agent to the peritoneal surfaces but may not contribute to control extra-peritoneal or systemic recurrences.…”

Section: Discussionmentioning

confidence: 99%

Interval debulking surgery with or without hyperthermic intraperitoneal chemotherapy in advanced-stage ovarian cancer: Single-institution cohort study

et al. 2022

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To evaluate the additive effects of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval debulking surgery (IDS) in patients with advanced-stage ovarian cancer. From January 2015 to February 2019, 123 patients with stages IIIC-IV ovarian cancer were treated with neoadjuvant chemotherapy (NAC) followed by IDS with optimal cytoreduction. Forty-three patients received IDS with HIPEC and 80 patients had IDS without HIPEC. The median follow-up period was 34.4 months. No differences in baseline characteristics in patients were found between the two groups. The IDS with HIPEC group had fewer median cycles of chemotherapy (P = 0.002) than the IDS group. The IDS with HIPEC group had a higher rate of high surgical complexity score (P = 0.032) and higher rate of complete resection (P = 0.041) compared to the IDS group. The times to start adjuvant chemotherapy were longer in the IDS with HIPEC group compared to the IDS group (P < 0.001). Postoperative grade 3 or 4 complications were similar in the two groups (P = 0.237). Kaplan-Meier analysis showed that HIPEC with the IDS group had better progression-free survival (PFS) (P = 0.010), while there was no difference in overall survival between the two groups (P = 0.142). In the multivariate analysis, HIPEC was significantly associated with better PFS (HR, 0.60; 95% CI, 0.39 - 0.93). The addition of HIPEC to IDS resulted in longer PFS than IDS without HIPEC not affecting the safety profile. Further research is needed to evaluate the true place of HIPEC in the era of targeted treatments.

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“…For the PM of gastrointestinal origin, obstruction-free survival has been proposed as a suitable end point to demonstrate the benefit of HIPEC [73]. One retrospective study on the patterns of recurrence following interval CRS and HIPEC showed a reduced incidence of peritoneal recurrence compared to previous reports that could be attributed to the use of HIPEC [74]. Theoretically, HIPEC should not just prolong PFS but OS as well.…”

Section: Clinical End Points For Evaluating the Benefit Of Hipecmentioning

confidence: 99%

Hyperthermic Intraperitoneal Chemotherapy in the Treatment Armamentarium of Epithelial Ovarian Cancer: Time to End the Dichotomy

Bhatt

Gléhen

2022

Visc Med

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Background: Advanced epithelial ovarian cancer (EOC) is an incurable disease with over 75% of the patients developing recurrence in the peritoneum. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment option for both first-line therapy and treatment of recurrence. In this article, we review the rationale and current evidence for performing HIPEC and the role of HIPEC in the light of targeted systemic therapies. Summary: There are few randomized trials and several retrospective studies on the role of HIPEC in the management of EOC. A 12-month-overall survival (OS) benefit of the addition of HIPEC to interval cytoreductive surgery (CRS) was demonstrated in 1 randomized trial following which HIPEC has been included as a treatment option for this indication in several national/international guidelines. One retrospective propensity score-matched analysis showed a 16-month OS benefit of adding HIPEC to primary CRS. One randomized trial showed no benefit of the addition of carboplatin HIPEC to secondary CRS over secondary CRS alone. For patients undergoing primary CRS and secondary CRS for recurrence, the results of ongoing randomized trials are needed to define the role of HIPEC in these situations. All clinical trials have shown that the morbidity of HIPEC performed after CRS is acceptable. Along with the emergence of HIPEC as a promising surgical therapy, targeted therapies like bevacizumab and poly adenosine diphosphate-ribose polymerase inhibitors have been developed that have shown a survival benefit in selected patients. In principle, HIPEC and targeted therapies work in different ways and it is plausible to assume that their benefit could be additive, and their combination should be evaluated in clinical trials. The impact of prognostic factors like the disease extent, pathological response to systemic chemotherapy (SC), the histological subtype and molecular profile on the benefit of HIPEC, and targeted therapies has not been evaluated in clinical trials. Key Messages: HIPEC is an important therapeutic strategy in the treatment of EOC. While its role in patients undergoing interval CRS has been established, the results of ongoing randomized trials are needed to define its benefit at other time points. The morbidity of HIPEC in addition to CRS is acceptable. More research is needed to define subgroups that benefit most from HIPEC based on the extent of disease, response to SC, histology, and molecular profile. The combination of HIPEC and maintenance therapies should be evaluated in well-designed randomized clinical trials that evaluate not just the survival benefit and morbidity but also the cost-effectiveness of each therapy.

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Pattern of recurrence after interval cytoreductive surgery and HIPEC following neoadjuvant chemotherapy in primary advanced stage IIIC/IVA epithelial ovarian cancer

Cited by 10 publications

References 25 publications

Surgical and systemic therapies for addressing occult disease in advanced epithelial ovarian cancer

Surgical and systemic therapies for addressing occult disease in advanced epithelial ovarian cancer

Interval debulking surgery with or without hyperthermic intraperitoneal chemotherapy in advanced-stage ovarian cancer: Single-institution cohort study

Hyperthermic Intraperitoneal Chemotherapy in the Treatment Armamentarium of Epithelial Ovarian Cancer: Time to End the Dichotomy

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