Genetic Clues May Help Predict Which Ovarian Cancer Patients Benefit Most from HIPEC
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Thanh Hue Dellinger et al. Mutational signatures as potential predictors of HIPEC response and recurrence in ovarian cancer.. J Clin Oncol 44, e17577-e17577(2026). DOI:10.1200/JCO.2026.44.16_suppl.e17577 Presented at the 2026 ASCO Annual Meeting (Abstract e17577)
What is HIPEC?
Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a treatment sometimes used during surgery for ovarian cancer. After visible tumors are removed, heated chemotherapy is circulated throughout the abdominal cavity to destroy remaining cancer cells.
Previous studies have shown that HIPEC can help some patients live longer, but doctors do not yet know which patients are most likely to benefit. This study looked for genetic biomarkers that might help predict treatment response.
Why Was This Study Done?
Researchers wanted to determine whether specific genetic patterns found in ovarian tumors could:
Predict which patients are more likely to respond well to HIPEC
Help identify patients at higher risk of cancer recurrence
Improve patient selection for HIPEC treatment in the future
How Was the Study Conducted?
Researchers analyzed tumor samples from 36 patients with epithelial ovarian cancer who underwent surgery followed by HIPEC at City of Hope between 2012 and 2022.
The study included patients with both:
Newly diagnosed ovarian cancer
Recurrent ovarian cancer
Using whole-exome sequencing, researchers examined tumor DNA to identify genetic mutations and mutational signatures—patterns of DNA damage that may provide clues about how a cancer behaves.
Patients were classified as either:
Good responders to HIPEC if they remained free of disease progression for a longer period after treatment
Poor responders if their cancer returned sooner
What Did Researchers Find?
A Genetic Signature Was Linked to Better HIPEC Response
Researchers found that patients whose tumors contained a genetic pattern called SBS5 were more likely to have a favorable response to HIPEC.
Half of the patients in the study were classified as good responders, and these patients had significantly better overall survival than poor responders.
Although scientists do not yet fully understand what causes the SBS5 signature, the finding suggests it could become a useful biomarker for predicting who may benefit most from HIPEC.
Another Signature Was Linked to Where Cancer Returned
The researchers also discovered that a different genetic signature, called SBS15, was more common among patients whose cancer returned only within the abdominal cavity (peritoneal recurrence).
Patients with lower levels of SBS15 appeared more likely to develop cancer recurrence outside the abdomen, known as extraperitoneal recurrence.
This finding may help doctors better understand recurrence patterns and identify patients who need closer monitoring after treatment.
Common Genetic Changes Were Identified
The most frequently mutated gene in the study was TP53, which was found in nearly half of all tumors. TP53 mutations are common in ovarian cancer and play a role in controlling cell growth and DNA repair.
Researchers also identified several important cancer-related pathways that were frequently altered, including:
TP53 pathway
RTK-RAS pathway
NOTCH pathway
PI3K pathway
What Do These Findings Mean for Patients?
This study suggests that genetic testing of ovarian tumors may eventually help doctors personalize HIPEC treatment.
In the future, biomarkers such as SBS5 could help identify patients who are most likely to benefit from HIPEC, while other markers like SBS15 may help predict how and where the cancer is most likely to recur.
More personalized treatment decisions could improve outcomes while helping patients avoid treatments that may be less effective for them.
Important Limitations
While the results are encouraging, several limitations should be considered:
The study included only 36 patients.
It was conducted at a single cancer center.
The findings have not yet been validated in larger patient populations.
The biological role of the SBS5 signature is not fully understood.
Because of these limitations, the findings should be considered preliminary until confirmed in future studies.
The Bottom Line
Researchers identified two genetic signatures that may help guide treatment decisions for ovarian cancer patients undergoing HIPEC. One signature (SBS5) was associated with better treatment response, while another (SBS15) was linked to recurrence patterns after treatment.
Although additional research is needed, these findings represent an important step toward more personalized care for ovarian cancer patients and may help doctors better identify who is most likely to benefit from HIPEC in the future.
Source: 2026 ASCO Annual Meeting, Abstract e17577. Findings presented at a scientific meeting should be considered preliminary until published in a peer-reviewed journal.
