HIPEC and immunotherapy for ovarian cancer

Ovarian cancer poses a significant global health burden, with mortality rates exceeding those of other gynecologic cancers. Despite initial sensitivity to chemotherapy and treatment with cytoreductive surgery, most patients experience recurrent disease and require multiple lines of therapy. Over time, relapses become increasingly resistant to treatment, ultimately leading to death. Although the disease is characterized by substantial heterogeneity, across histologic subtypes, molecular profiles, and tumor microenvironments, most patients still receive largely uniform treatment. This one-size-fits-all approach reflects a gap between our growing biological understanding and the availability of treatment options capable of targeting these differences. Therapeutic strategies such as hyperthermic intraperitoneal chemotherapy (HIPEC) and immune checkpoint inhibitors have emerged as promising approaches, yet many critical questions remain. Specifically, what is the long-term efficacy of HIPEC when added to interval cytoreductive surgery? How effective is HIPEC in routine clinical practice outside the trial setting? How can perioperative care be optimized? Which tumor micro-environmental or molecular features explain sensitivity or resistance to these treatments? Are there specific populations, such as those with BRCA mutations or other homologous recombination defects that are more or less likely to respond? Why does only a small minority of ovarian cancer patients benefit from immunotherapy and who are they?
This thesis addresses these questions through a combination of clinical and translational research, aiming to better define the role of HIPEC and immunotherapy in ovarian cancer and to identify potential predictive biomarkers. Part I focuses on HIPEC, and Part II on immune checkpoint inhibition, both in the setting of advanced-stage ovarian cancer.