Sequential Yttrium-90 radioembolization integrated with multimodal therapy for platinum-resistant ovarian cancer liver metastases

Highlights

• •Sequential yttrium-90 radioembolization used for ovarian liver metastases.
• •Demonstrates feasibility of repeated liver-directed therapy.
• •Integrated with systemic therapy, surgery, and nodal radiation.
• •Maintained hepatic control while preserving functional liver reserve.
• •Achieved durable disease control beyond two years.

Abstract

Background

Hepatic metastases from ovarian cancer are associated with poor prognosis, particularly in patients with platinum-resistant disease, and treatment options are limited. We present a case illustrating the feasibility and potential benefit of sequential locoregional therapy using yttrium-90 radioembolization for liver-dominant metastatic ovarian carcinoma.

Case Presentation

A 62-year-old female with stage IVB high-grade serous ovarian carcinoma and unresectable hepatic metastases underwent neoadjuvant platinum chemotherapy followed by selective internal radiation therapy targeting dominant liver lesions. Therapy was repeated in a staged manner alongside non-platinum systemic therapy, cytoreductive surgery, and nodal radiation as clinically indicated. Imaging and functional assessments were used to evaluate tumor response and liver function throughout treatment.

Sequential radioembolization achieved durable hepatic disease control over a two-year period. The treated right hepatic lobe underwent gradual atrophy with compensatory hypertrophy of the left lobe, preserving overall liver function and enabling repeated therapy. Integration with systemic therapy and surgery allowed continued management of peritoneal disease. Treatment was well tolerated, with manageable laboratory and clinical toxicities. Imaging demonstrated a significant reduction in tumor size and resolution of metabolic activity, supporting effective locoregional control.

Conclusion

Sequential yttrium-90 radioembolization is a feasible and potentially durable locoregional strategy for patients with unresectable, platinum-resistant ovarian cancer liver metastases. When integrated with systemic therapy and surgery, this approach may provide meaningful disease control while preserving liver function. Prospective studies are warranted to further define patient selection, optimal sequencing, and clinical outcomes for this emerging therapy.

1. Introduction

Ovarian cancer is a leading cause of gynecologic cancer mortality and is frequently diagnosed at an advanced stage (Webb & Jordan, 2024). Despite cytoreductive surgery and systemic chemotherapy, recurrence is common, and prognosis is poor when parenchymal hepatic metastases develop. Therapeutic options remain limited, although novel strategies are emerging (Kurnit et al., 2021).

Yttrium-90 (Y-90) Selective Internal Radiation Therapy (SIRT) is an established locoregional treatment for primary and secondary hepatic malignancies, particularly hepatocellular carcinoma and colorectal metastases to the liver (Tong et al., 2016). Its role in metastatic ovarian carcinoma, however, is poorly characterized. Published data are limited to small registries and case reports, discussed below, and no guidelines currently recommend its routine use.

We present a patient with stage IVB high-grade serous ovarian carcinoma and unresectable hepatic metastases who underwent Y-90 SIRT as a salvage strategy. This case highlights the feasibility of SIRT in platinum-resistant disease and underscores the importance of multidisciplinary collaboration between gynecologic oncology and interventional radiology for liver-dominant progression.

2. Case

A 62-year-old woman presented with new abdominal pain and fullness. Contrast-enhanced CT showed two large cystic adnexal masses, peritoneal and omental implants, and a 9.8  cm low-attenuation mass in the right hepatic lobe (Fig. 1). Biopsy of an omental implant confirmed high-grade serous Müllerian carcinoma, consistent with stage IVB ovarian cancer.

Fig. 1.

Baseline Examination. Initial CT of the abdomen and pelvis (left image: sagittal; right image: coronal) demonstrates large cystic adnexal masses and an irregular right posterior hepatic lobe mass measuring up to 9.8 cm. The hepatic lesion demonstrates central hypoattenuation, likely reflecting necrosis. In the setting of bilateral prominent cystic adnexal masses, these findings are suspicious for hepatic metastatic disease. Incidental bilateral renal cysts are also noted.

The patient was not considered a candidate for hepatectomy due to lesion size, location, and overall disease burden. She began neoadjuvant platinum-based chemotherapy and was referred for Y-90 SIRT targeting the dominant hepatic lesion. Pre-treatment angiographic mapping was performed to define hepatic arterial anatomy, calculate radiation dose, and ensure safe treatment delivery while minimizing non-target embolization. Two weeks later, bland embolization of a parasitized right inferior phrenic artery was performed, followed by segmental Y-90 administration via the right hepatic artery (Fig. 2).

Fig. 2.

Y-90 Treatment #1. This figure from the initial Y-90 treatment is representative of the general mapping and treatment workflow performed during the subsequent treatment sessions, although the fourth treatment specifically targeted the caudate lobe. The top left image demonstrates planar scintigraphy following Technetium-99 m macroaggregated albumin (Tc-99 m MAA) administration, with regions of interest drawn over the lungs and liver for lung shunt fraction calculation, measuring 6.4%, within accepted safety limits for radioembolization. The bottom left image demonstrates angiography of the right hepatic artery through which Y-90 microspheres were subsequently administered. The right image demonstrates post-treatment SPECT/CT with radiotracer uptake localized within the right hepatic lobe, corresponding to the lesion of concern.

Approximately three months after SIRT and systemic therapy, the dominant hepatic lesion decreased to 8.8  cm with improved peritoneal disease (Fig. 3). A new 1.8  cm PET-avid hepatic lesion developed adjacent to the treatment zone. She underwent repeat lobar Y-90 treatment and transitioned to non-platinum chemotherapy for suspected platinum resistance. Due to bulk-related symptoms, she subsequently underwent interval cytoreductive surgery that included an exploratory laparotomy with abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy with optimal cytoreduction. Follow-up PET/CT two months after the repeat Y-90 treatment and one month after surgery demonstrated no residual hepatic or peritoneal avidity (Fig. 4).

Fig. 3.

Follow-Up After Initial Y-90 Treatment. The left image demonstrates a truncated sagittal CT image from a chest, abdomen, and pelvis examination obtained three months after initial radioembolization, showing interval decrease in size of the right hepatic lobe lesion to a maximum diameter of 8.8 cm. Four months post-treatment, FDG PET/CT was performed (right image, axial view), demonstrating hypometabolism within the treated right hepatic lobe lesion, although with interval development of a small adjacent hypermetabolic satellite lesion (arrow). The more anterior hypodense structure represents the gallbladder.

Fig. 4.

Follow-Up After Second Y-90 Treatment. The left image demonstrates an FDG PET/CT obtained two months after second Y-90 radioembolization, showing persistent hypometabolism of the treated right hepatic lesion with interval resolution of the previously identified hypermetabolic satellite lesion. The right image demonstrates a sagittal CT of the liver showing interval decrease in the lesion size to a maximum diameter of 7 cm.

During surveillance, the treated right hepatic lobe progressively atrophied with compensatory hypertrophy of the left lobe. The dominant hepatic lesion remained morphologically visible, however, it had decreased in size to 7 cm and it no longer demonstrated FDG avidity on PET imaging. This was considered compatible with post-treatment changes, including treatment-related necrosis following Y-90 radioembolization, rather than a persistently metabolically active tumor. A PET-avid paraaortic node during a chemotherapy break was treated with external-beam radiation. Approximately 17 months after initial presentation, imaging showed progression along the superolateral margin of the hepatic ablation zone and new portocaval lymphadenopathy (Fig. 5). She underwent repeat Y-90 to the right lobe, followed one month later by segmental Y-90 treatment of the caudate lobe, followed by additional systemic therapy.

Fig. 5.

Imaging Findings Prompting Additional Y-90 Treatment. Axial FDG PET/CT obtained nine months after the second Y-90 radioembolization demonstrates peripheral hypermetabolic activity surrounding the right hepatic lesion (white arrows) and a newly enlarged, metabolically active perihepatic lymph node (red arrow). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Approximately two years from initial presentation, therapy was discontinued due to grade 4 hyperbilirubinemia and grade 3 liver enzyme elevation. Over this time period, the patient maintained overall meaningful locoregional disease control and sufficient functional liver reserve to permit multiple sequential Y-90 treatments (Fig. 6). A timeline of key imaging findings and Y-90 treatments can be found in Supplementary Material Table 1.

Fig. 6.

Follow-Up After Third and Fourth Y-90 Treatments. Axial CT of the abdomen and pelvis obtained approximately two months after the fourth Y-90 treatment demonstrates interval increase in size of the right hepatic lesion to a maximum diameter of 7.3 cm. This may reflect post-treatment change, although residual or progressive disease cannot be excluded pending continued imaging follow-up. This examination reflects the patient’s treatment course spanning approximately 22 months, during which serial Y-90 radioembolization treatments provided sustained locoregional disease management prior to the onset of grade 4 hyperbilirubinemia and grade 3 liver enzyme elevation.

3. Discussion

This case uniquely supports sequential Y-90 radioembolization as a feasible treatment strategy for patients with unresectable, platinum-resistant ovarian cancer liver metastases—a commonly encountered high-risk population with limited therapeutic options. Hepatic involvement is associated with worse survival outcomes, and treatment options are often constrained by platinum resistance and the limited feasibility of complete surgical resection (Zhao et al., 2020, Gardner et al., 2020, O'Neill et al., 2017, Foote et al., 2018, Wright et al., 2016, Bogani et al., 2026). Locoregional therapies are therefore emerging as potential strategies to improve hepatic disease control.

Y-90 SIRT is a guideline-endorsed locoregional therapy for unresectable hepatocellular carcinoma and colorectal liver metastases and is increasingly used for metastases arising from other primaries. In the multicenter Radiation-Emitting SIR-Spheres in Non-resectable liver tumor (RESiN) registry, 481 patients received Y-90 SIRT for non-colorectal liver metastases across 12 tumor types. Of these, only 10 patients had ovarian primaries. Despite the limited sample size, these patients had encouraging outcomes, with 1-year overall survival of 90% and progression-free survival of 70%, among the highest in the registry (Zhou et al., 2024). However, the limited sample and lack of disease-specific outcomes preclude definitive conclusions, emphasizing the need for further investigation.

A more focused retrospective study from 2021 evaluated 9 heavily pretreated, platinum-resistant ovarian cancer patients with liver metastases, subsequently managed with transarterial radioembolization (TARE). Median overall survival was 9 months, with median local progression at 6 months. Treatment was well-tolerated with no high-grade adverse events. Importantly, repeat TARE was not reported in this series (Lacayo et al., 2021).

Our case adds to the literature, demonstrating the feasibility of sequential Y-90 radioembolization for hepatic-dominant, platinum-resistant ovarian cancer metastases. Unlike prior reports limited to single treatments, this patient underwent four Y-90 sessions, integrated with neoadjuvant platinum chemotherapy, debulking surgery, non-platinum therapy, and nodal radiation. Additionally, radioembolization-induced right-lobe atrophy with compensatory left-lobe hypertrophy helped preserve overall liver function, facilitating repeated therapy, bridging to surgery, and maintaining hepatic disease control during transitions in systemic therapy (Teo et al., 2016). This approach yielded prolonged survival extending beyond two years, likely due to combined peritoneal and hepatic disease control.

The success of modern radioembolization relies on personalized radiation dosimetry. Some of the more common side effects of SIRT include mild post-embolic syndrome (diarrhea, nausea, vomiting) and laboratory toxicities such as hyperbilirubinemia and elevated liver enzymes. Serious complications, such as radiation pneumonitis and radiation-induced liver disease, are minimized through a meticulous multi-step process that ensures the prescribed dose effectively treats the tumor while sparing normal parenchyma. This process is guided by detailed anatomical mapping with diagnostic angiography and a Technetium-99 m macroaggregated albumin (Tc-99 m MAA) lung shunt study. Such assessments are important both for calculating the therapeutic radiation dose and for reducing the risk of non-target embolization (Riaz et al., 2014).

Objectively assessing treatment response after radioembolization is challenging, as tumor necrosis often precedes size reduction. Combining anatomical and functional imaging can improve evaluation, though no standard Y-90 SIRT protocol exists. Response Evaluation Criteria in Solid Tumors (RECIST) provides an evaluation framework that is most widely used for systemic therapies, although its application to ablative locoregional therapies has known limitations (Fournier et al., 2022). For example, SIRT-induced necrosis and inflammation can transiently enlarge lesions, potentially mimicking disease progression by RECIST criteria. For these reasons, a multimodal assessment of response is essential.

Although strict RECIST parameters alone may underestimate the treatment effect, broader multimodal assessment and consideration of the full clinical context underscore the meaningful benefit achieved during therapy in our patient. For instance, three months after initial SIRT, the treated lesion did not meet the size reduction criteria for “complete” or even “partial response.” However, complete resolution of the lesion’s hypermetabolism on PET scan provides compelling evidence of a favorable response (Obrzut et al., 2017). Additionally, sequential treatments ultimately produced a decrease in size sufficient to qualify for a “partial response.” The effectiveness of locoregional control is further supported by survival beyond a two-year period. Taken altogether, this case’s success is founded on integration with systemic therapy, personalized dosimetry, functional liver preservation, safety, measurable imaging response, and survival benefit over a two-year period.

4. Conclusion

In conclusion, sequential Y-90 SIRT is a rational and potentially durable locoregional option for unresectable, platinum-resistant ovarian cancer liver metastases. With meticulous dosimetric planning and multimodal imaging, it can be effectively integrated into a multidisciplinary treatment paradigm, serving as a salvage or adjunctive therapy to maintain hepatic control and complement systemic or surgical approaches. Given the prevalence of hepatic involvement and limited treatment options in platinum-resistant disease, selected patients may derive meaningful benefit from this approach. Prospective studies are warranted to formally define the role of Y-90 SIRT and to establish its role in this setting.

Declaration of Generative AI and AI-Assisted Technologies in the Manuscript Preparation Process.

During the preparation of this work the authors used ChatGPT for correction of grammar, decreasing word count, and reference formatting. OpenEvidence was used to aid the authors in identifying scientific articles relevant to this case report. After using these tools, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.

Written informed consent was obtained from the patient for publication of this case report and accompanying images.

CRediT authorship contribution statement

Anne Wahl: Writing – review & editing, Writing – original draft, Resources, Project administration, Methodology, Funding acquisition, Conceptualization. Jacob Fryer: Writing – review & editing, Writing – original draft, Resources, Project administration, Methodology, Funding acquisition. Courtney Vazquez: Writing – original draft, Software, Methodology, Data curation, Conceptualization. Scott Kim: Writing – review & editing, Software, Resources, Project administration. James Mega: Writing – review & editing, Supervision, Data curation, Conceptualization. Emily Penick: Writing – review & editing, Visualization, Supervision, Methodology, Conceptualization.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary data

The following are the Supplementary data to this article:

Supplementary Data 1

Timeline of key imaging findings and Y-90 treatments.