Radiation Therapy Combined With Checkpoint Blockade Immunotherapy for Metastatic Undifferentiated Pleomorphic Sarcoma of the Maxillary Sinus With a Complete Response

Abstract

Background: Undifferentiated pleomorphic sarcoma (UPS) of the maxillary sinus is an extremely rare malignancy of the head and neck. Surgery is the mainstay of treatment for UPS; however, proximity to vital structures makes it challenging to achieve negative surgical margins. Adjuvant therapy including radiation therapy with or without chemotherapy is generally indicated. Despite advances in multimodality treatment, objective response rates to available therapies and prognosis of metastatic UPS remain dismal. Immunotherapy has become a fourth cornerstone of cancer therapy and checkpoint blockade immunotherapy is a standard of care for recurrent or metastatic cisplatin-refractory head and neck squamous cell carcinoma. Checkpoint blockade immunotherapy is being studied in metastatic sarcoma, including UPS, and while initial results are promising, objective response rates remain below 20%. However, adding radiation therapy to checkpoint blockade immunotherapy has been shown, in both preclinical and retrospective clinical studies, to have combinatorial effects on both local and metastatic disease. Thus, further investigation into the effects of radiation therapy combined with immunotherapy in head and neck sarcomas is warranted.Case Presentation: We present a case of metastatic, chemotherapy-refractory, UPS of the maxillary sinus in a 55-year-old male treated with checkpoint blockade immunotherapy combined with radiation, which resulted in a complete response.Conclusions: This is the first report to our knowledge of metastatic UPS treated with a combination of radiation and dual agent checkpoint blockade immunotherapy. Further investigation is warranted to study the effects of this combination in patients with metastatic UPS that fail to respond to currently available therapies.

Immunotherapy for sarcomas: new frontiers and unveiled opportunities

“…10 14 Several individual case reports have shown that sarcoma patients treated with ICB achieve a positive response or complete remission. [15][16][17][18][19] All patients presented with unique sarcoma subtypes and with varying levels of checkpoint receptor expression, thus identifying commonalities between the positive responses was challenging. The SARC028 (NCT02301039) was one of the first multicenter phase II trials evaluating the effectiveness of ICB in sarcoma.…”

Regression of advanced maxillary sinus cancer with orbital invasion by combined chemotherapy and immunotherapy: A one‑year follow‑up case report

“…It is known that high PD-L1 expression levels and a high mutational burden are correlated with higher response rates to PD-1-based immunotherapies (8). Previous studies have revealed the effect of combining immunotherapy and radiotherapy on maxillary sinus cancer (8,9) indicating favorable responses. Thus, it may be used as an alternative for this patient if he elected radiotherapy, despite that radiation toxicity must be considered due to the history of the patient with radiotherapy for nasopharyngeal cancer.…”

“…There have been numerous studies on the use of the combination of chemotherapy and radiotherapy for maxillary sinus cancer investigating the effect of the combination of immunotherapy and radiotherapy on maxillary sinus cancer (8,9). However, to date, no study has investigated the combination of chemotherapy and immunotherapy for maxillary sinus cancer.…”

Primary undifferentiated pleomorphic sarcoma of the rectum: A case report and review of the literature

“…Therefore, meaningful responses to nivolumab-ipilimumab combination therapy and pembrolizumab therapy have been reported in pretreated UPS [19.20]. The combination of immune checkpoint inhibitors and radiotherapy for UPS that was refractory to conventional chemotherapy achieved complete response (CR) in a case report [21]. Currently, the effects of preoperative radiotherapy and immune checkpoint inhibitor therapy on retroperitoneal UPS are being explored [22].…”