Tumour microenvironment characterisation to stratify patients for hyperthermic intraperitoneal chemotherapy in high-grade serous ovarian cancer (OVHIPEC-1).

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with Stage III ovarian cancer following interval cytoreductive surgery (CRS). Optimising patient selection is essential to maximise treatment efficacy and avoid overtreatment. This study aimed to identify biomarkers that predict HIPEC benefit by analysing gene signatures and cellular composition of tumours from participants in the OVHIPEC-1 trial. METHODS: Whole-transcriptome RNA sequencing data were retrieved from high-grade serous ovarian cancer (HGSOC) samples from 147 patients obtained during interval CRS. We performed differential gene expression analysis and applied deconvolution methods to estimate cell-type proportions in bulk mRNA data, validated by histological assessment. We tested the interaction between treatment and potential predictors on progression-free survival using Cox proportional hazards models. RESULTS: While differential gene expression analysis did not yield any predictive biomarkers, the cellular composition, as characterised by deconvolution, indicated that the absence of macrophages and the presence of B cells in the tumour microenvironment are potential predictors of HIPEC benefit. The histological assessment confirmed the predictive value of macrophage absence. CONCLUSION: Immune cell composition, in particular macrophages absence, may predict response to HIPEC in HGSOC and these hypothesis-generating findings warrant further investigation. CLINICAL TRIAL REGISTRATION: NCT00426257.

Preferences and considerations for interval cytoreductive surgery in advanced ovarian cancer: The patient's perspective.

OBJECTIVE: Treatment of advanced-stage ovarian cancer contains cytoreductive surgery (CRS) and chemotherapy. Achieving successful CRS (≤ 1 cm residual disease) is prognostically important, but may not be feasible peri-operatively while still risking complications. Therefore, patients' treatment expectations are important to discuss. We investigated patient considerations for interval CRS. METHODS: Patients with advanced-stage ovarian cancer planned for interval CRS completed a questionnaire about the impact of chance of successful CRS, survival benefit and becoming care-dependent on decision-making regarding CRS. The questionnaire included a vignette study, in which patients repeatedly chose between two treatment scenarios with varying levels for chance of successful CRS, survival benefit and risk of complications including stoma. Patient preferences were analyzed, including differences between patients aged < 70 and ≥ 70 years. RESULTS: Among 85 included patients, 31 (37%) patients considered interval CRS worthwhile irrespective of survival benefit and 33 (39%) irrespective of chance of successful surgery. However, 34 patients (41%) considered interval CRS only worthwhile if survival benefit was > 12 months, while 41 (49%) thought so if chance of successful surgery was ≥ 25%. Older patients considered these factors more important. Overall, 27% considered becoming permanently dependent of home care unacceptable. In the vignette study (n = 72) risk of complications and stoma were considered less important than chance of successful CRS and survival benefit. CONCLUSION: Survival benefit, chance of successful surgery and becoming care-dependent are important factors in patient's decision for interval CRS, while risk of complications and stoma are less important. Our results are useful in shared decision-making for interval CRS in ovarian cancer.

Effects of a combined exercise and dietary intervention on body composition, physical functioning and fatigue in patients with ovarian cancer: results of the PADOVA trial.

BACKGROUND: Guidelines recommend to include exercise and dietary advice in standard care for patients with cancer, based on evidence primarily derived from patients with breast cancer. Its applicability to patients with ovarian cancer is uncertain due to differences in patient characteristics and treatments. The PADOVA trial examined the effectiveness of a combined exercise and dietary intervention on fat-free mass (FFM), physical functioning, and fatigue. METHODS: In total, 81 patients with ovarian cancer were randomised to the exercise and dietary intervention (n = 40) or control (n = 41) group. Measurements were performed before chemotherapy, after chemotherapy, and 12 weeks later. FFM was assessed by bioelectrical impedance analysis, and physical functioning and fatigue were assessed using questionnaires. Intervention effects were assessed on an intention-to-treat basis using linear mixed models. RESULTS: FFM and physical functioning increased, and fatigue decreased significantly over time in both groups. No significant difference between the groups were found for FFM (ß = -0.5 kg; 95% CI = -3.2; 2.1), physical functioning (ß = 1.4; 95% CI = -5.4; 8.3) and fatigue (ß = 0.7; 95% CI = -1.5; 2.8). CONCLUSIONS: During treatment, both groups improved in FFM, physical functioning, and fatigue. The intervention group, however, did not demonstrate additional benefits compared to the control group. This highlights the need for caution when extrapolating findings from different cancer populations to patients with ovarian cancer.

Outcomes of patients with early stage mucinous ovarian carcinoma: a Dutch population-based cohort study comparing expansile and infiltrative subtypes.

OBJECTIVE: This study aimed to assess the outcomes of patients with early stage mucinous ovarian carcinoma based on subtype (expansile vs infiltrative). METHODS: We retrospectively analyzed all surgically treated patients with mucinous ovarian carcinoma in the Netherlands (2015-2020), using data from national registries. Subtypes were determined, with any ambiguities resolved by a dedicated gynecologic pathologist. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I were categorized into full staging, fertility-sparing, or partial stagings. Outcomes were overall survival and recurrence free survival, and recurrence rates. RESULTS: Among 409 identified patients, 257 (63%) had expansile and 152 (37%) had infiltrative tumors. Patients with expansile tumors had FIGO stage I more frequently (n=243, 95% vs n=116, 76%, p<0.001). For FIGO stage I disease, patients with expansile and infiltrative tumors underwent similar proportions of partial (n=165, 68% vs n=78, 67%), full (n=32, 13% vs n=23, 20%), and fertility-sparing stagings (n=46, 19% vs n=15, 13%) (p=0.139). Patients with expansile FIGO stage I received less adjuvant chemotherapy (n=11, 5% vs n=24, 21%, p<0.001), exhibited better overall and recurrence free survival (p=0.006, p=0.012), and fewer recurrences (n=13, 5% vs n=16, 14%, p=0.011). Survival and recurrence rates were similar across the expansile extent of staging groups. Patients undergoing fertility-sparing staging for infiltrative tumors had more recurrences compared with full or partial stagings, while recurrence free survival was similar across these groups. Full staging correlated with better overall survival in infiltrative FIGO stage I (p=0.022). CONCLUSIONS: While most patients with FIGO stage I underwent partial staging, those with expansile had better outcomes than those with infiltrative tumors. Full staging was associated with improved overall survival in infiltrative, but not in expansile FIGO stage I. These results provide insight for tailored surgical approaches.

Demographic, clinical, and sociocognitive determinants related to physical activity and dietary intake in patients with ovarian cancer: A cross-sectional study.

OBJECTIVE: To study physical activity and dietary intake among patients with ovarian cancer and to examine which demographic, clinical, and sociocognitive determinants are associated with these behaviours. METHODS: This cross-sectional study included 139 patients with ovarian cancer scheduled for (neo)adjuvant chemotherapy. Physical activity was measured with the Physical Activity Scale for the Elderly questionnaire (PASE). Dietary intake was measured with a questionnaire assessing energy and protein intake and a questionnaire assessing adherence to the World Cancer Research Fund (WCRF) lifestyle recommendations. Demographic, clinical, and sociocognitive (e.g., self-efficacy) determinants of physical activity and dietary intake were examined using backward linear regression analyses. RESULTS: Patients reported a median PASE score of 50 (IQR 24-94), a mean ± SD dietary intake of 1831 ± 604 kcal/day and 76 ± 27 g protein/day. Patients adhered to 3 out of 5 WCRF lifestyle recommendations. The absence of comorbidities, lower physical outcome expectations, and higher cancer specific outcome expectations were independently associated with higher physical activity levels. Higher age, lower cancer specific outcome expectations, and higher diet-related self-efficacy were significantly associated with adhering to more WCRF lifestyle recommendations, whilst no variables associated with total caloric or protein intake were identified. CONCLUSIONS: Patients with ovarian cancer have low physical activity levels and a suboptimal diet, particularly low fruit and vegetable consumption and dietary fibre intake. Interventions aiming to improve physical activity and dietary intake could focus on increasing self-efficacy and outcome expectations, and should consider age and comorbidity as factors that may impact behaviour. TRIAL REGISTRATION: Netherlands Trial Registry NTR6300.

Health state utility and health-related quality of life measures in patients with advanced ovarian cancer.

Purpose: Measuring health-related quality of life (HRQoL) in ovarian cancer patients is critical to understand the impact of disease and treatment. Preference-based HRQoL measures, called health state utilities, are used specifically in health economic evaluations. Real-world patient-reported data on HRQoL and health state utilities over the long-term course of ovarian cancer are limited. This study aims to determine HRQoL and health state utilities in different health states of ovarian cancer. Methods: This cross-sectional, multicenter study included patients with stage III-IV ovarian cancer in six health states: at diagnosis, during chemotherapy, after cytoreductive surgery (CRS), after chemotherapy, in remission, and at first recurrence. HRQoL was measured using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30, and the ovarian cancer-specific module OV28. Health state utilities were assessed using the EuroQol five-dimension five-level (EQ-5D-5L) questionnaire. Descriptive analyses were performed for each health state. Results: Two hundred thirty-two patients participated, resulting in 319 questionnaires. Median age was 66 years. The lowest HRQoL was observed during chemotherapy and shortly after CRS. Physical and role functioning were most affected and the highest symptom prevalence was observed in the fatigue, nausea, pain, dyspnea, gastrointestinal, neuropathy, attitude, and sexuality domains. Patients in remission had the best HRQoL. Mean utility values ranged from 0.709 (±0.253) at diagnosis to 0.804 (±0.185) after chemotherapy. Conclusions: This study provides clinicians with a valuable resource to aid in patient counseling and clinical decision-making. The utilities, in particular, are crucial for researchers conducting economic analyses to inform policy decisions.

Is routine admission to a critical care setting following hyperthermic intraperitoneal chemotherapy for ovarian cancer necessary?

INTRODUCTION: Hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly being used in patients with stage III ovarian cancer undergoing interval cytoreductive surgery (CRS). It is uncertain whether routine postoperative admission to a critical care setting after CRS-HIPEC is necessary. This study aims to estimate the incidence of patients requiring critical care, and to create a prediction model to identify patients who may forego admission to a critical care setting. METHODS: We analyzed 154 patients with primary ovarian cancer undergoing interval CRS-HIPEC at two Dutch centers between 2007 and 2021. Patients were routinely admitted to a critical care setting for 12-24 h. Patients that received critical support as defined by pre-specified definitions were retrospectively identified. Logistic regression analysis with backward selection was used to predict the need for critical care and the model was validated using bootstrapping. RESULTS: Thirty-eight percent of patients received postoperative critical care, consisting mainly of hemodynamic interventions. Independent predictors of critical care were blood loss, norepinephrine dose during surgery, and age (bootstrapped AUC = 0.76). Using a probability cut-off of 20%, one-third of patients are defined as low-risk for requiring critical care, with a negative predictive value of 0.88. CONCLUSIONS: The majority of patients,primarily undergoing low to intermediate complexity surgeries, did not receive critical care interventions after CRS-HIPEC. Selective admission to a critical care setting may be warranted and its feasibility and safety needs to be evaluated prospectively. Our prediction model can help identify patients in whom admission to a critical care setting may be omitted. Hospital costs and burden on critical care units will benefit from patient selection.

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial.

BACKGROUND: The OVHIPEC-1 trial previously showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in improved progression-free and overall survival compared with cytoreductive surgery alone at 4·7 years of follow-up in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. We report the final survival outcomes after 10 years of follow-up. METHODS: In this open-label, randomised, controlled, phase 3 trial, patients with primary epithelial stage III ovarian cancer were recruited at eight HIPEC centres in the Netherlands and Belgium. Patients were eligible if they were aged 18-76 years, had not progressed during at least three cycles of neoadjuvant carboplatin plus paclitaxel, had a WHO performance status score of 0-2, normal blood counts, and adequate renal function. Patients were randomly assigned (1:1) to undergo interval cytoreductive surgery without HIPEC (surgery group) or with HIPEC (100 mg/m2 cisplatin; surgery-plus-HIPEC group). Randomisation was done centrally by minimisation with a masked web-based allocation procedure at the time of surgery when residual disease smaller than 10 mm diameter was anticipated, and was stratified by institution, previous suboptimal cytoreductive surgery, and number of abdominal regions involved. The primary endpoint was progression-free survival and a secondary endpoint was overall survival, analysed in the intention-to-treat population (ie, all randomly assigned patients). This study is registered with ClinicalTrials.gov, NCT00426257, and is closed. FINDINGS: Between April 1, 2007, and April 30, 2016, 245 patients were enrolled and followed up for a median of 10·1 years (95% CI 8·4-12·9) in the surgery group (n=123) and 10·4 years (95% CI 9·5-13·3) in the surgery-plus-HIPEC group (n=122). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival 10·7 months [95% CI 9·6-12·0]) and 109 (89%) patients in the surgery-plus-HIPEC group (14·3 months [12·0-18·5]; hazard ratio [HR] 0·63 [95% CI 0·48-0·83], stratified log-rank p=0·0008). Death occurred in 108 (88%) patients in the surgery group (median overall survival 33·3 months [95% CI 29·0-39·1]) and 100 (82%) patients in the surgery-plus-HIPEC group (44·9 months [95% CI 38·6-55·1]; HR 0·70 [95% CI 0·53-0·92], stratified log-rank p=0·011). INTERPRETATION: These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery. FUNDING: Dutch Cancer Foundation (KWF Kankerbestrijding).

Exploring international differences in ovarian cancer care: a survey report on global patterns of care, current practices, and barriers.

OBJECTIVE: Although global disparities in survival rates for patients with ovarian cancer have been described, variation in care has not been assessed globally. This study aimed to evaluate global ovarian cancer care and barriers to care. METHODS: A survey was developed by international ovarian cancer specialists and was distributed through networks and organizational partners of the International Gynecologic Cancer Society, the Society of Gynecologic Oncology, and the European Society of Gynecological Oncology. Respondents received questions about care organization. Outcomes were stratified by World Bank Income category and analyzed using descriptive statistics and logistic regressions. RESULTS: A total of 1059 responses were received from 115 countries. Respondents were gynecological cancer surgeons (83%, n=887), obstetricians/gynecologists (8%, n=80), and other specialists (9%, n=92). Income category breakdown was as follows: high-income countries (46%), upper-middle-income countries (29%), and lower-middle/low-income countries (25%). Variation in care organization was observed across income categories. Respondents from lower-middle/low-income countries reported significantly less frequently that extensive resections were routinely performed during cytoreductive surgery. Furthermore, these countries had significantly fewer regional networks, cancer registries, quality registries, and patient advocacy groups. However, there is also scope for improvement in these components in upper-middle/high-income countries. The main barriers to optimal care for the entire group were patient co-morbidities, advanced presentation, and social factors (travel distance, support systems). High-income respondents stated that the main barriers were lack of surgical time/staff and patient preferences. Middle/low-income respondents additionally experienced treatment costs and lack of access to radiology/pathology/genetic services as main barriers. Lack of access to systemic agents was reported by one-third of lower-middle/low-income respondents. CONCLUSIONS: The current survey report highlights global disparities in the organization of ovarian cancer care. The main barriers to optimal care are experienced across all income categories, while additional barriers are specific to income levels. Taking action is crucial to improve global care and strive towards diminishing survival disparities and closing the care gap.

Safety and feasibility of hyperthermic intraperitoneal chemotherapy during interval cytoreductive surgery in patients with advanced high-grade serous ovarian, fallopian tube, peritoneal cancer in an Australian context.

AIMS: To assess the safety and feasibility of hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreduction surgery (CRS) in advanced high-grade serous ovarian, fallopian tube and peritoneal cancer within an Australian context. METHODS: Data were collected from 25 consecutive patients undergoing CRS and HIPEC from December 2018 to July 2022 at the Peritoneal Malignancy Service at the Mater Hospital Brisbane, Australia. Data collected included demographics, clinical variables, surgical procedures and complications and intra-operative and post-operative indexes of morbidity. RESULTS: Twenty-five women who underwent CRS and HIPEC from December 2018 to July 2022 were included in analysis. Findings indicate that CRS with HIPEC is associated with low morbidity. CONCLUSION: While judicious patient selection is imperative, HIPEC during CRS was well tolerated by all patients and morbidity was comparable to results from the previously reported OVHIPEC-1 trial. HIPEC appears to be a safe and feasible addition to CRS for the treatment of advanced ovarian cancer in Australian practice.

Evaluation of external validity of the OVHIPEC-1 trial in a real-world population.

OBJECTIVE: The OVHIPEC-1 trial (Phase III randomised clinical trial for stage III ovarian carcinoma randomising between interval cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy) showed improved survival when interval cytoreductive surgery (CRS) was combined with hyperthermic intraperitoneal chemotherapy in patients with stage III epithelial ovarian cancer (EOC). The authors compared the control arm of the trial with a real-world population treated in the Netherlands during the same period to explore generalizability of the trial results. METHODS: For this nationwide comparative cohort study, all patients with EOC undergoing interval CRS between 2007 and 2016 were identified from the Netherlands Cancer Registry if they fulfilled the eligibility criteria of OVHIPEC-1 (n = 1376). Patient and treatment characteristics, and overall survival (OS) were compared between trial and real-world populations. RESULTS: Age, comorbidity, BRCA status, histologic subtype, and residual disease were similar in trial and real-world patients. Trial patients had a better performance status, higher socioeconomic status, and underwent bowel surgery more often. In a real-world setting, patients more often received more than six cycles. The difference in OS between the trial and the real-world populations was not statistically significant (unadjusted hazard ratio, 1.09 [95% confidence interval, 0.87-1.37]; P = 0.44). CONCLUSION: Despite differences in patient characteristics, OS of patients treated in the control arm of OVHIPEC-1 was similar to patients treated outside the trial. The trial population accurately represents real-world patients with stage III EOC undergoing interval CRS in terms of outcome.

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.

Progression-free survival and overall survival after BRCA1/2-associated epithelial ovarian cancer: A matched cohort study.

INTRODUCTION: Germline BRCA1/2-associated epithelial ovarian cancer has been associated with better progression-free survival and overall survival than sporadic epithelial ovarian cancer, but conclusive data are lacking. METHODS: We matched 389 BRCA1-associated and 123 BRCA2-associated epithelial ovarian cancer patients 1:1 to sporadic epithelial ovarian cancer patients on year of birth, year of diagnosis, and FIGO stage (< = IIA/> = IIB). Germline DNA test was performed before or after epithelial ovarian cancer diagnosis. All patients received chemotherapy. We used Cox proportional hazards models to estimate the associations between mutation status (BRCA1 or BRCA2 versus sporadic) and progression-free survival and overall survival. To investigate whether DNA testing after epithelial ovarian cancer diagnosis resulted in survival bias, we performed additional analyses limited to BRCA1/2-associated epithelial ovarian cancer patients with a DNA test result before cancer diagnosis (n = 73 BRCA1; n = 9 BRCA2) and their matched sporadic controls. RESULTS: The median follow-up was 4.4 years (range 0.1-30.1). During the first three years after epithelial ovarian cancer diagnosis, progression-free survival was better for BRCA1 (HR 0.88, 95% CI 0.74-1.04) and BRCA2 (HR 0.58, 95% CI 0.41-0.81) patients than for sporadic patients. Overall survival was better during the first six years after epithelial ovarian cancer for BRCA1 (HR 0.7, 95% CI 0.58-0.84) and BRCA2 (HR 0.41, 95% CI 0.29-0.59) patients. After surviving these years, survival benefits disappeared or were in favor of the sporadic patients. CONCLUSION: For epithelial ovarian cancer patients who received chemotherapy, we confirmed survival benefit for BRCA1 and BRCA2 germline pathogenic variant carriers. This may indicate higher sensitivity to chemotherapy, both in first line treatment and in the recurrent setting. The observed benefit appears to be limited to a relatively short period after epithelial ovarian cancer diagnosis.

Surgical treatment for clinical early-stage expansile and infiltrative mucinous ovarian cancer: can staging surgeries safely be omitted?

PURPOSE OF REVIEW: Mucinous ovarian cancers (MOCs) are categorized into infiltrative and expansile subtypes. These subtypes have different characteristics and prognoses. Patients with clinical early-stage disease of both subtypes currently undergo surgical staging (peritoneal washing, biopsies, omentectomy). Peritoneal and lymph node metastases of expansile MOC are rare, but whereas lymph node sampling (LNS) is omitted in these patients, peritoneal staging is not. Therefore, we collected all available MOC data to determine whether staging surgeries could safely be omitted in clinical early-stage expansile and infiltrative MOC. RECENT FINDINGS: Current literature confirms that peritoneal metastases are rare in expansile MOC: more than 90% of patients have early-stage disease. Only 3.4% of the patients with clinical early-stage expansile MOC had positive peritoneal washings at surgical staging. Patients with infiltrative MOC were diagnosed more frequently with advanced-stage disease (21-54%). Moreover, upstaging clinical early-stage infiltrative MOC based on positive cytology, peritoneum and omentum metastases occurred in 10.3% of the patients. Therefore, we recommend that patients with early-stage infiltrative MOC undergo peritoneal staging and LNS. However, in addition to omitting LNS, we can also safely recommend omitting peritoneal staging in patients with clinical early stage expansile MOC. SUMMARY: Peritoneal metastases are rare in clinical early-stage expansile MOC and peritoneal staging can therefore safely be omitted.

Effect of HIPEC according to HRD/BRCAwt genomic profile in stage III ovarian cancer: Results from the phase III OVHIPEC trial.

The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin to interval cytoreductive surgery improves recurrence-free (RFS) and overall survival (OS) in patients with stage III ovarian cancer. Homologous recombination deficient (HRD) ovarian tumors are usually more platinum sensitive. Since hyperthermia impairs BRCA1/2 protein function, we hypothesized that HRD tumors respond best to treatment with HIPEC. We analyzed the effect of HIPEC in patients in the OVHIPEC trial, stratified by HRD status and BRCAm status. Clinical data and tissue samples were collected from patients included in the randomized, phase III OVHIPEC-1 trial. DNA copy number variation (CNV) profiles, HRD-related pathogenic mutations and BRCA1 promotor hypermethylation were determined. CNV-profiles were categorized as HRD or non-HRD, based on a previously validated algorithm-based BRCA1-like classifier. Hazard ratios (HR) and corresponding 99% confidence intervals (CI) for the effect of RFS and OS of HIPEC in the BRCAm, the HRD/BRCAwt and the non-HRD group were estimated using Cox proportional hazard models. Tumor DNA was available from 200/245 (82%) patients. Seventeen (9%) tumors carried a pathogenic mutation in BRCA1 and 14 (7%) in BRCA2. Ninety-one (46%) tumors classified as BRCA1-like. The effect of HIPEC on RFS and OS was absent in BRCAm tumors (HR 1.25; 99%CI 0.48-3.29), and most present in HRD/BRCAwt (HR 0.44; 99%CI 0.21-0.91), and non-HRD/BRCAwt tumors (HR 0.82; 99%CI 0.48-1.42), interaction P value: 0.024. Patients with HRD tumors without pathogenic BRCA1/2 mutation appear to benefit most from treatment with HIPEC, while benefit in patients with BRCA1/2 pathogenic mutations and patients without HRD seems less evident.