Ten-year treatment outcomes of consolidation hyperthermic intraperitoneal chemotherapy for ovarian cancer (HIPEC-KOV-03R)

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Abstract

Objective

We aimed to evaluate the long-term efficacy of consolidation hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with primary epithelial ovarian cancer.

Methods

This retrospective cohort study included patients who underwent second-look surgery either with or without HIPEC after having complete or partial response to primary cytoreductive surgery and adjuvant platinum-based chemotherapy between January 1991 and December 2003 at Seoul St. Mary’s Hospital. The 10-year progression-free survival (PFS), overall survival (OS), and toxicity within postoperative 28 days were investigated.

Results

A total of 87 patients were identified, 44 (50.6%) received second-look surgery with HIPEC whereas 43 (49.4%) received only second-look surgery. The 10-year PFS and OS were significantly longer in the HIPEC group compared with the control group (PFS, 53.6% vs. 34.9%, log-rank p=0.009; OS, 57.0% vs. 34.5%, log-rank p=0.025). Multivariable analysis identified HIPEC as an independent favorable prognostic factor for PFS (adjusted hazard ratio [HR]=0.42; 95% confidence interval [CI]=0.23–0.77; p=0.005) but not for OS (adjusted HR=0.58; 95% CI=0.32–1.07; p=0.079). The more common adverse events in the HIPEC group were thrombocytopenia (90.9% vs. 68.3%, p=0.005), elevated liver enzymes (65.9% vs. 29.3%, p=0.002), and wound complications (18.2% vs. 2.4%, p=0.032). However, these adverse events were reversible and did not delay subsequent consolidation chemotherapy.

Conclusion

The consolidation HIPEC demonstrated a significant improvement in 10-year PFS but not OS, with acceptable toxicity in patients with primary epithelial ovarian cancer. Further randomized controlled trials are warranted to confirm these results.

Synopsis

An improved 10-year progression-free survival (PFS) and overall survival (OS) were observed in patients who received consolidation hyperthermic intraperitoneal chemotherapy (HIPEC). Multivariable analysis identified HIPEC as an independent favorable prognostic factor for PFS but not for OS. Adverse events of HIPEC were tolerable.

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Most cited references 31

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Cancer statistics, 2022

Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2022)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.

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The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies.

Erik von Elm, Douglas G. Altman, Matthias Egger … (2014)

Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. 18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the Web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.

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Ovarian cancer development and metastasis.

Ernst Lengyel (2010)

The biology of ovarian carcinoma differs from that of hematogenously metastasizing tumors because ovarian cancer cells primarily disseminate within the peritoneal cavity and are only superficially invasive. However, since the rapidly proliferating tumors compress visceral organs and are only temporarily chemosensitive, ovarian carcinoma is a deadly disease, with a cure rate of only 30%. There are a number of genetic and epigenetic changes that lead to ovarian carcinoma cell transformation. Ovarian carcinoma could originate from any of three potential sites: the surfaces of the ovary, the fallopian tube, or the mesothelium-lined peritoneal cavity. Ovarian cacinoma tumorigenesis then either progresses along a stepwise mutation process from a slow growing borderline tumor to a well-differentiated carcinoma (type I) or involves a genetically unstable high-grade serous carcinoma that metastasizes rapidly (type II). During initial tumorigenesis, ovarian carcinoma cells undergo an epithelial-to-mesenchymal transition, which involves a change in cadherin and integrin expression and up-regulation of proteolytic pathways. Carried by the peritoneal fluid, cancer cell spheroids overcome anoikis and attach preferentially on the abdominal peritoneum or omentum, where the cancer cells revert to their epithelial phenotype. The initial steps of metastasis are regulated by a controlled interaction of adhesion receptors and proteases, and late metastasis is characterized by the oncogene-driven fast growth of tumor nodules on mesothelium covered surfaces, causing ascites, bowel obstruction, and tumor cachexia.

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Author and article information

Journal

Journal ID (nlm-ta): J Gynecol Oncol

Journal ID (iso-abbrev): J Gynecol Oncol

Journal ID (publisher-id): JGO

Title: Journal of Gynecologic Oncology

Publisher: Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology; Japan Society of Gynecologic Oncology

ISSN (Print): 2005-0380

ISSN (Electronic): 2005-0399

Publication date Collection: November 2023

Publication date (Electronic): 27 June 2023

Volume: 34

Issue: 6

Electronic Location Identifier: e72

Affiliations

[1 ]Department of Obstetrics and Gynecology, Daejeon St. Mary’s Hospital, The Catholic University of Korea, Daejeon, Korea.

[2 ]Center for Gynecologic Cancer, National Cancer Center, Goyang, Korea.

[3 ]Biostatistics Collaboration Team, Research Core Center, National Cancer Center, Goyang, Korea.

[4 ]Department of Obstetrics and Gynecology, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea.

Author notes

Correspondence to Sung Jong Lee. Department of Obstetrics and Gynecology, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul 06591, Korea. orlando@ 123456catholic.ac.kr

Correspondence to Myong Cheol Lim. Center for Gynecologic Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea. mclim@ 123456ncc.re.kr , gynlim@ 123456gmail.com

Author information

Ji Geun Yoo https://orcid.org/0000-0001-5359-8729

Ji Hyun Kim https://orcid.org/0000-0002-4746-5572

Eun Young Park https://orcid.org/0000-0003-2430-5282

Imhyeon Kim https://orcid.org/0000-0001-8444-6234

Myong Cheol Lim https://orcid.org/0000-0001-8964-7158

Sung Jong Lee https://orcid.org/0000-0002-6077-2649

Article

DOI: 10.3802/jgo.2023.34.e72

PMC ID: 10627752

PubMed ID: 37417300

SO-VID: b27d453b-b7d3-4a7a-916e-855385e1f53d

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 27 December 2022

Date revision received : 18 April 2023

Date accepted : 13 May 2023

Funding

Funded by: National Cancer Center, CrossRef https://doi.org/10.13039/501100003645;

Award ID: NCC 2110790

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Ten-year treatment outcomes of consolidation hyperthermic intraperitoneal chemotherapy for ovarian cancer (HIPEC-KOV-03R)

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Abstract

Objective

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Karger: Oncology

Most cited references 31

Cancer statistics, 2022

The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies.

Ovarian cancer development and metastasis.

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