Hyperthermic intraperitoneal chemotherapy for epithelial ovarian cancer: A meta-analysis.

BACKGROUND: The value of hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of cytoreductive surgery (CRS) for epithelial ovarian cancer (EOC) is controversial and its use remains experimental in most national and international guidelines. We wished to systematically evaluate all available evidence. METHODS: A comprehensive review of data from MEDLINE, EMBASE, and Cochrane Library databases was conducted from the first report on HIPEC in EOC till April 3, 2022. Progression-free survival (PFS) and overall survival (OS) were compared between the HIPEC and control groups. This meta-analysis was registered with PROSPERO (CRD42021265810). RESULTS: Fifteen studies (10 case-control studies and 5 randomized controlled trials [RCTs]) were included in the present meta-analysis. Based on the time interval between the last systemic chemotherapy exposure and timing of CRS +/- HIPEC, all studies and patients' cohorts we classified into recent (<6 months; n = 9 studies/patients cohorts) and non-recent (≥6 months, n = 8 studies/patients cohorts) chemotherapy exposure groups. In the recent chemotherapy exposure group, HIPEC was associated with improvement of both PFS (HR, 0.585; 95% CI, 0.422-0.811) and OS (HR, 0.519; 95% CI, 0.346-0.777). On the contrary, in the non-recent chemotherapy exposure group, HIPEC failed to significantly affect PFS (HR, 1.037; 95% CI, 0.684-1.571) or OS (HR, 0.932; 95% CI, 0.607-1.430). Consistent results were observed in subsequent sensitivity analyses. CONCLUSION: Our present meta-analysis demonstrates that the value of HIPEC at CRS for EOC appears to depend on the timing of the last systemic chemotherapy exposure. Future trials are awaited to define the role of HIPEC in EOC.

British Gynaecological Cancer Society recommendations and guidance on patient-initiated follow-up (PIFU).

The National Cancer Survivorship Initiative through the National Health Service (NHS) improvement in the UK started the implementation of stratified pathways of patient-initiated follow-up (PIFU) across various tumor types. Now the initiative is continued through the Living With and Beyond Cancer program by NHS England. Evidence from non-randomized studies and systematic reviews does not demonstrate a survival advantage to the long-established practice of hospital-based follow-up regimens, traditionally over 5 years. Evidence shows that patient needs are inadequately met under the traditional follow-up programs and there is therefore an urgent need to adapt pathways to the needs of patients. The assumption that hospital-based follow-up is able to detect cancer recurrences early and hence improve patient prognosis has not been validated. A recent survey demonstrates that follow-up practice across the UK varies widely, with telephone follow-up clinics, nurse-led clinics and PIFU becoming increasingly common. There are currently no completed randomized controlled trials in PIFU in gynecological malignancies, although there is a drive towards implementing PIFU. PIFU aims to individualize patient care, based on risk of recurrence and holistic needs, and optimizing resources. The British Gynaecological Cancer Society wishes to provide the gynecological oncology community with guidance and a recommendations statement regarding the value, indications, and limitations of PIFU in endometrial, cervical, ovarian, and vulvar cancers in an effort to standardize practice and improve patient care.

Is there a role for HIPEC in ovarian cancer?

Hyperthermic intraperitoneal chemotherapy (HIPEC) is promoted by some as a standard treatment for peritoneal carcinomatosis of epithelial ovarian cancer (EOC) and other tumor entities, despite lack of robust data supporting this. Publicly available evidence addressing the value of HIPEC in EOC is rather inconclusive, revealing contradictory and inconsistent results while some studies even report harm to the patients from a higher morbidity. On this ground, we cannot recommend the implementation and use of HIPEC outside of a randomized clinical trial setting.

Long term combination treatment with bevacizumab, pegylated liposomal doxorubicin and regional abdominal hyperthermia in platinum refractory ovarian cancer: a case report and review of the literature.

BACKGROUND: Platinum resistance constitutes a therapeutic challenge in the treatment of ovarian cancer, with overall unsatisfactory response rates to standard chemotherapy and correspondingly low survival. Regional abdominal hyperthermia and bevacizumab are treatment options that have both shown the capacity to improve the results of standard chemotherapy in the platinum-resistant situation, when added to the treatment schedule. CASE REPORT: We report on a 29-year-old patient with primary platinum-refractory ovarian cancer, who was treated with a combination of pegylated liposomal doxorubicin, regional abdominal hyperthermia and bevacizumab in a four-week cycle over a long-term period of 38 months. Due to an excellent clinical and radiologic response resulting in stable disease, with a concomitant mild toxicity profile consisting only of intermitted diarrhoea and mild fatigue [corrected] , the treatment was continued in an ambulatory setting. DISCUSSION: To our knowledge we describe the first experience with combination treatment of pegylated liposomal doxorubicin with regional abdominal hyperthermia and bevacizumab in a long term setting of almost 2 years. Excellent response with comparably low toxicity was demonstrated. Further evaluation as a therapeutic option in this heavily pretreated and highly palliative patient population is warranted.

Regional abdominal hyperthermia combined with systemic chemotherapy for the treatment of patients with ovarian cancer relapse: Results of a pilot study.

PURPOSE: Due to the poor prognosis of patients with ovarian cancer relapse (OCR), newer strategies are warranted to improve the therapeutic index. We performed a prospective phase I/II-study of regional abdominal hyperthermia (RHT) combined with systemic chemotherapy in OCR patients in order to evaluate outcome, efficacy and tolerance. MATERIALS AND METHODS: OCR patients with an Eastern Cooperative Oncology Group status <2, without any thromboembolic disease or severe cardiovascular co-morbidities, and pre-treated with at least one systemic chemotherapy regimen due to epithelial ovarian cancer were enrolled into the present study. RHT was applied using a SIGMA 60 applicator and a Hybrid-System SIGMA-Eye/MRT composed of a 1.5T-MRT and a Sigma-Eye-applicator. RESULTS: Overall, 36 OCR patients were enrolled. The majority of the patients (>80%) were classified as platinum resistant. The most common chemotherapeutic agent applied was pegylated-liposomal-doxorubicin (47.2%) followed by carboplatin (16.6%) and topotecan (13.9%). One patient (2.8%) achieved a complete remission (CR), 12 patients (33.3%) yielded a partial remission (PR) and 16 patients (44.4%) developed a progressive disease (PD). In platinum-sensitive patients we observed higher response (57.1% versus 31%) and lower progression rates (28.6% versus 48.3%) than in platinum-resistant patients. Eleven patients (30.5%) discontinued treatment due to toxicity. The main toxicity was a haematological one with grade 3/4 anaemia, leucopenia and thrombocytopenia occurring in 13.9%, 5.6% and 8.3%, respectively. Median overall survival was 12 months (range: 1-48), while median progression-free survival was 5 months (range: 0.5-34). CONCLUSIONS: Our results demonstrate the feasibility of RHT combined with systemic treatment. Prospective phase III trials are warranted to evaluate the benefit and efficacy in heavily pre-treated patients with OCR.