Asan Medical Center Team Led by Professor Hyun-Woong Cho Establishes Evidence for Selecting Candidates for Hyperthermic Intraperitoneal Chemotherapy Based on Changes in Blood Markers

In Patients With Poor Chemotherapy Response, HIPEC Reduces Recurrence Risk by 58 Percent and Mortality Risk by 71 Percent Compared With Non Treated Group

▲Professor Hyun-Woong Cho of the Department of Obstetrics and Gynecology at Asan Medical Center

Ovarian cancer is characterized by its tendency to spread to multiple sites within the abdominal cavity, and in many cases, cancer cells have already disseminated to the peritoneum by the time the disease is detected. For these patients, hyperthermic intraperitoneal chemotherapy, or HIPEC, is administered following tumor debulking surgery. This approach involves delivering heated anticancer drugs directly into the abdominal cavity, enabling the eradication of microscopic residual tumors on the peritoneum and ultimately improving survival outcomes.

However, the therapeutic benefits of hyperthermic intraperitoneal chemotherapy (HIPEC) are not uniform across all patients. As a result, there has been a clear need for reliable criteria to identify patients who are most likely to derive substantial benefit from this treatment.

According to a recent announcement, a research team led by Professor Hyun-Woong Cho of the Department of Obstetrics and Gynecology at Asan Medical Center analyzed blood test data from 213 patients with stage 3 or higher ovarian cancer. The findings showed that among patients with a poor response to chemotherapy, those who underwent HIPEC experienced a 58 percent reduction in the risk of ovarian cancer recurrence and a 71 percent reduction in the risk of death compared with those who did not receive the treatment.

The research team confirmed that the benefits of HIPEC were particularly pronounced in patients whose tumors showed a relatively slow rate of reduction during preoperative chemotherapy prior to tumor debulking surgery.

This study is expected to contribute to improving treatment efficiency and overall survival by providing evidence that a simple blood test can help predict which ovarian cancer patients are most likely to benefit from HIPEC.

Ovarian cancer, which has the highest mortality rate among gynecologic malignancies, is a highly intractable disease marked by frequent recurrence and a five-year survival rate of less than 50 percent. Because it presents with few specific symptoms in its early stages, approximately 80 percent of patients are diagnosed at an advanced stage, when the cancer has already spread throughout the abdominal cavity, corresponding to stages 3 and 4.

HIPEC is a treatment in which visible tumors are surgically removed through an open abdominal procedure, followed by the infusion of anticancer drugs heated to approximately 42 degrees Celsius into the abdominal cavity to eradicate microscopic cancer cells. Because the therapy involves administering heated chemotherapy during surgery, it carries a risk of complications, but it is effective in eliminating cancer cells that are vulnerable to heat. Despite these advantages, there has been no established biomarker to predict which ovarian cancer patients are most likely to benefit from HIPEC.

During chemotherapy for ovarian cancer, blood tests are routinely performed to measure levels of the tumor marker CA125. CA125 is a substance that rises abnormally in the blood when ovarian cancer develops, and its level decreases as tumors shrink in response to chemotherapy. For this reason, CA125 is widely used as an indicator of treatment response.

A research team led by Professor Hyun-Woong Cho of the Department of Obstetrics and Gynecology at Asan Medical Center analyzed blood test data from 213 patients with stage 3 and 4 ovarian cancer who underwent at least three CA125 tests during the first 100 days of initial chemotherapy.

To assess trends in CA125 changes, the research team utilized the chemotherapy response predictor KELIM, a tool developed by researchers at the University of Lyon in France. KELIM mathematically quantifies the rate of CA125 decline during chemotherapy, with lower values indicating a poorer tumor response to anticancer drugs.

Among the 213 patients included in the study, 159 underwent HIPEC following tumor debulking surgery, while 54 received tumor debulking surgery alone. Using a treatment predictor index cutoff of 1.0, the research team classified patients with values below 1.0 as the poor chemotherapy response group and those with values of 1.0 or higher as the good chemotherapy response group, and then compared the effects of HIPEC between the two groups.

As a result, among patients in the poor chemotherapy response group, the risk of ovarian cancer recurrence was reduced by 58 percent and the risk of death by 71 percent compared with those who did not receive HIPEC. Progression free survival also differed markedly, with a median of approximately 10 months in the non HIPEC group versus about 20 months in the HIPEC treated group, representing a twofold increase. In terms of overall survival, the non-treated group showed a median survival of approximately 45 months, whereas in the HIPEC group more than half of the patients remained alive throughout the observation period, making the median overall survival difficult to determine.

In particular, the benefits of HIPEC were most pronounced among patients in the poor chemotherapy response group who were aged 60 years or older, had high grade serous ovarian cancer, or were diagnosed with stage 4 disease.

By contrast, in the good chemotherapy response group, no statistically significant differences in survival were observed according to whether HIPEC was performed. These findings indicate that patients who respond well to standard chemotherapy can achieve sufficient outcomes with conventional treatment alone, whereas those with a poor response to chemotherapy may improve survival through the addition of HIPEC.

Professor Hyun-Woong Cho of the Department of Obstetrics and Gynecology at Asan Medical Center stated, “Chemotherapy plays a central role in the treatment of ovarian cancer, but patients with a poor response to anticancer drugs have often shown unfavorable outcomes even after undergoing surgery and chemotherapy. This study is particularly meaningful in that it demonstrates that combining surgery with HIPEC can effectively reduce the risks of recurrence and death in this patient group.”

He added, “Because the effectiveness of HIPEC can be predicted simply through a CA125 blood test, this approach is expected to make a significant contribution to establishing patient tailored treatment strategies and improving survival outcomes.”

The study was recently published in the International Journal of Gynecological Cancer, a leading international journal in the field of gynecologic oncology, which has an impact factor of 4.7.