We successfully treated an unresectable locally advanced UCOGC case with conversion surgery after FOLFIRINOX therapy. PC is the most aggressive solid tumor in humans and has a very poor prognosis [5, 6]. Even if no metastasis is detected, it is often diagnosed as unresectable locally advanced pancreatic cancer (LAPC); the primary resectable PC is present in only 15–20% of all patients [7]. However, the number of cases of conversion surgery has been increasing due to the development of novel chemotherapeutic regimens. Of these regimens, FOLFIRINOX has been reported to improve the response rate of LAPC and the rate of conversion surgery considerably [7, 8]. To the best of our knowledge, there have been no reported cases of conversion surgery for UCOGC after FOLFIRINOX, and the current case is the first report.
UCOGC is extremely rare, with an incidence of 1.4% for invasive PCs and 0.4% for resected PCs [2]. The prognosis of UCOGC is inconsistent, because the disease is so rare that it is difficult to evaluate the prognosis by stage [1], and most UGOCG cases were found at the advanced stage and recurred early after resection [9]. Another reason is that UCOGC was not defined until 2010 when WHO integrated two subtypes, giant cell tumors (GCTs) with osteoclast-like cells and pleomorphic GCTs, as UCOGC [10]. In general, UCOGC is a rapidly growing tumor with abundant blood flow, often presenting as a large tumor with hemorrhage and necrosis [11, 12]. UCOGC is also an aggressive tumor, so composite resection with invaded adjacent organs such as the stomach, jejunum, colon, left kidney [13], diaphragm, and common hepatic artery is often needed [14]. Further investigations with large sample sizes are required to identify the molecular characteristics of UCOGC and establish a treatment strategy for UCOGC to achieve conversion surgery.
Conversion surgery may improve the prognosis of patients with PC. The number of cases with conversion therapy for PDAC has been increasing, owing to the recent advances in chemotherapy [6]. Although the efficacy of chemotherapy for UCOGC has not yet been fully evaluated, standard chemotherapy regimens for pancreatic cancer, including FOLFILINOX, have been selected because UCOGC is considered a variant of ductal adenocarcinoma of the pancreas [9]. In addition to FOLFIRINOX, there are reports that gemcitabine was effective against UCOGC [15]. Gemcitabine is often used in combination with nab-paclitaxel, capecitabine, or S-1. In addition to conventional chemotherapy, immune checkpoint inhibitors (ICIs) have recently attracted increasing attention for the treatment of various cancers, including PC [5]. IHC for PD-L1 was positive in 65% to 80% of UCOGC cases, and these cases showed poor prognosis [16, 17]. However, PD-L1-positive UCOGC showed a marked response to ICI, both in primary UCOGC tumors and metastatic diseases [18]. In the current case, IHC for PD-L1 was strongly positive in the surgically resected specimen, suggesting that ICIs may have been effective. Routine assessment of immune-related markers such as programmed death 1 (PD-1) and PD-L1 for tumor biopsy specimens at initial diagnosis could provide therapeutic options other than FOLFIRINOX to establish precision treatment for PC in the era of immunotherapy. Another important examination for patients with PDAC is germline genetic testing for BRCA pathogenic variant. For patients who have germline BRCA mutation, after at least 16 weeks of platinum-based chemotherapy such as FOLFIRINOX without disease progression, the PARP inhibitor olaparib is recommended [19]. Although olaparib is usually used in the second-line setting, we consider BRCA status of the patient in the current study is very important because the patient could be susceptible to tumor recurrence after conversion surgery. Since the patient underwent 20 weeks of preoperative FOLFIRINOX with favorable response, we plan to check BRCA status in the near future.
