World journal of surgical oncology · 2025
Pathological complete response to pembrolizumab in recurrent retroperitoneal dedifferentiated liposarcoma with high tumor mutational burden: a case report.
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Abe Shun, Zhou Qiliang, Ariizumi Takashi, Sugai Mika, Kawachi Yusuke, Ando Takuya, Hirose Yuki, Ishikawa Hirosuke, Miura Kohei, Ichikawa Hiroshi, Takizawa Kazuyasu, Shimada Yoshifumi, Sakata Jun, Kobayashi Takashi, Kawashima Hiroyuki, Wakai Toshifumi
Аннотация
BACKGROUND: Dedifferentiated liposarcoma (DDLPS), a common subtype of retroperitoneal soft tissue sarcoma, generally shows a limited response to conventional chemotherapy. Recently, immune checkpoint inhibitors (ICIs) have demonstrated promising activity against DDLPS. However, predictive biomarkers for response remain unclear. We present a case of recurrent retroperitoneal DDLPS with a high tumor mutational burden (TMB), demonstrating a pathological complete response (pCR) to pembrolizumab. We also explore the association between the response to ICIs and the tumor microenvironment, including programmed death-ligand 1 (PD-L1), tumor-infiltrating lymphocytes (TILs), and tumor-associated macrophages (TAMs).
CASE PRESENTATION: A 73-year-old man undergoing hormone therapy for metastatic prostate cancer was incidentally found to have a multilobulated retroperitoneal tumor in the right iliac fossa during routine follow-up imaging. He underwent macroscopically complete removal of the tumor, which was histologically diagnosed as DDLPS. Eight months later, recurrence with peritoneal dissemination was detected. He received doxorubicin (6 cycles) followed by pazopanib (13 weeks) and eribulin (3 cycles). The response to all these treatments was progressive disease. Comprehensive genomic profiling of the primary tumor revealed high TMB (13 mutations/megabase). Pembrolizumab 400 mg was administered every 6 weeks. After 11 cycles, imaging revealed a partial response with a 56.7% decrease in target lesions. However, discontinuation of pembrolizumab was required due to ICI-induced inflammatory arthritis. In a second radical surgery, 9 disseminated lesions were excised. Histological examination showed extensive hyalinization and necrosis with no residual viable tumor cells, indicating pCR. He remains alive and well without disease 15 months after the second surgery. Immunohistochemistry of the primary tumor revealed negative PD-L1 expression, low TIL density, and markedly high TAM density.
CONCLUSIONS: This is the first reported case of recurrent retroperitoneal DDLPS with high TMB achieving pCR to pembrolizumab. High TMB and high TAM density in the tumor microenvironment may be predictive biomarkers for the response to ICIs in DDLPS.
CASE PRESENTATION: A 73-year-old man undergoing hormone therapy for metastatic prostate cancer was incidentally found to have a multilobulated retroperitoneal tumor in the right iliac fossa during routine follow-up imaging. He underwent macroscopically complete removal of the tumor, which was histologically diagnosed as DDLPS. Eight months later, recurrence with peritoneal dissemination was detected. He received doxorubicin (6 cycles) followed by pazopanib (13 weeks) and eribulin (3 cycles). The response to all these treatments was progressive disease. Comprehensive genomic profiling of the primary tumor revealed high TMB (13 mutations/megabase). Pembrolizumab 400 mg was administered every 6 weeks. After 11 cycles, imaging revealed a partial response with a 56.7% decrease in target lesions. However, discontinuation of pembrolizumab was required due to ICI-induced inflammatory arthritis. In a second radical surgery, 9 disseminated lesions were excised. Histological examination showed extensive hyalinization and necrosis with no residual viable tumor cells, indicating pCR. He remains alive and well without disease 15 months after the second surgery. Immunohistochemistry of the primary tumor revealed negative PD-L1 expression, low TIL density, and markedly high TAM density.
CONCLUSIONS: This is the first reported case of recurrent retroperitoneal DDLPS with high TMB achieving pCR to pembrolizumab. High TMB and high TAM density in the tumor microenvironment may be predictive biomarkers for the response to ICIs in DDLPS.