Successful secondary radical operation on unretractable metastatic platinum-sensitive recurrent ovarian cancer by immunotherapy: a case report

Abstract

Background: Although rechallenge with platinum-based chemotherapy is effective for most platinum-sensitive recurrent ovarian cancer (ROC) patients, there is still a subset of patients who have no responses to the standard care. Overcoming multidrug resistance (MDR) is a top priority in oncology clinics, but it remains intricate. It is difficult for clinicians to manage unretractable ROC when conventional therapy yields no results. The rational and effective use of immunotherapy will contribute to the clinical benefit of these patients, especially in patients without approved immunotherapy biomarkers. Here we present a case of successful secondary radical surgery for unretractable metastatic MDR ROC by immunotherapy based on her immune-infiltrating tumor microenvironment signatures.

Case description: A 57-year-old woman, diagnosed with IC2 stage high-grade serous ovarian cancer in 2015, underwent immediate ultra-radical cytoreductive surgery followed by 6 cycles of platinum-containing adjuvant chemotherapy. After nearly 37 months of disease-free status, the woman complained of spontaneous pain from the right subcostal margin for 1 month and was diagnosed with ROC accompanied by multiple unretractable colorectal and hepatic metastases. Standard chemotherapies were ineffective and quickly resulted in disease progression and grade IV myelosuppression followed impaired gastrointestinal function. Notably, after standard chemotherapy, the patient was tested negative for all immune biomarkers, but multiple fluorescence immunohistochemistry indicated that her tumor tissue was significantly infiltrated with the cluster of differentiation 8 (CD8) T cells and natural killer (NK) cells, implying potential benefits of immunotherapy. Then changed to 3 cycles of intravenous pembrolizumab, the main pelvic tumor and hepatic metastases showed significant shrinkage and achieved partial response, but the disease progressed after 8.7 months. Subsequently, arterial perfusion with pembrolizumab was performed combined with the chemotherapy. A comfortingly partial response was achieved again that enabled the patient to successfully undergo a secondary radical surgery for colorectal and liver metastases. Since that time the patient's postoperative course has been favorable, and she remains disease-free at present for at least 17 months.

Conclusions: Immune infiltration signatures of the tumor microenvironment could serve as an indication for immunotherapy in patients with unretractable platinum-sensitive ROC with MDR. In addition, the introduction of immunotherapy might bring some degree of chemotherapy resensitization.

Keywords: Platinum-sensitive recurrent ovarian cancer; case report; immunotherapy; multiple metastases; second radical surgery.

Figure 1

Timeline of cancer treatments from October 2015 to January 2021 with radiologic findings and pathological slice observations. The red circles represent hepatic metastasis before the initiation of treatment and during the treatment for recurrences (April 2019 to October 2019). The 1^st important partial response occurred after 6 months (October 2019). The red arrowheads show the vaginal stump bump before and during the treatment for recurrences (April 2019 to January 2021). HE staining of metastatic tumors of colorectal and liver (×100). Surgery I: total uterus and double appendages resection + omentum resection + appendix resection + pelvic lymph nodes and para-aortic lymph nodes and presacral lymph nodes dissection; Surgery II: pelvic floor mass resection + rectal resection + partial sigmoid colectomy + sigmoid colostomy + partial small bowel resection + intestinal anastomosis; Surgery III: cholecystectomy + resection of multiple hepatic metastases; IHPC, intraperitoneal hyperthermic perfusion chemotherapy; PD, progressive disease; PR, partial response; RFS, recurrent free survival; PFS, progression-free survival; HE, hematoxylin and eosin.

Figure 2

Evolution of tumor marker tests (CA125, HE4, and AFP) from May 2019 to January 2021 with a corresponding timeline of chemotherapy and Pembrolizumab treatment for recurrent ovarian cancer. The dotted line box shows the main findings of the biomarkers for immunotherapy. Immunohistochemical staining for PD-L1 (Dako, 22C3 PharmDx) expression (×200). CA125, cancer antigen 125; HE4, human epididymis protein 4; AFP, alpha-fetoprotein; PD-L1, programmed death-ligand 1; MSS, microsatellite stability; bTMB, blood tumor mutational burden; TIME, tumor immune microenvironment; NK, natural killer cell.

Figure 3

Immune cell subset characteristics in the tumor microenvironment. (A) Multiple fluorescence immunohistochemical images for tumor (panCK, Abcam, ab7753), T cells (CD8, Abcam, ab178089), macrophages (CD68/HLA-DR, Abcam, ab213363/Abcam, ab92511), and NK cells (CD56, Abcam, ab75813) in the vaginal stump bump sample. Multiplex stained slides were scanned using a Vectra Polaris Quantitative Pathology Imaging System (Akoya Biosciences) at 20 nm wavelength intervals from 440 to 780 nm with a fixed exposure time and an absolute magnification of ×200. (B) Quantitative analysis of the immune composition in the tumor and stroma. (C) Percentage of immunoreactive cells in the tumor component. panCK, pan-cytokeratin; CD8, cluster of differentiation 8; CD68, cluster of differentiation 68; HLA-DR, human leukocyte antigen-DR isotype; CD56, cluster of differentiation 56.