Successful Salvage Chemotherapy with FOLFIRINOX for Recurrent Mixed Acinar Cell Carcinoma and Ductal Adenocarcinoma of the Pancreas in an Adolescent Patient
A 15-year-old boy presented in November 2009 with a 3.2-cm tumor of the head of the pancreas and multiple diffuse liver metastases (fig. ). Liver and kidney function tests were within normal limits, serum alpha-fetoprotein (AFP) was elevated (400 U/ml). Biopsy of the liver mass revealed a malignant tumor with acinar cell differentiation, bringing up the differential diagnosis of acinar cell carcinoma, or a mixed tumor with acinar cell differentiation including pancreatoblastoma.\nChemotherapy was initiated with two cycles of cisplatin and doxorubicin (PLADO regimen), resulting in a partial response of the primary tumor and the liver metastases. Based on the good response, a Whipple duodenopancreatectomy and simultaneous wedge resection of the metastases of the left liver with ligation of the right portal vein were performed in March 2010. Two additional cycles of the same chemotherapy were given postoperatively.\nThe metastases of the right liver lobe were resected by hemihepatectomy of the right liver, any other lesions in the remnant liver were removed by wedge resection. In addition, focally infiltrated parts of the diaphragm were also resected. Altogether, this accounted for a surgical tumor reduction of about 90%. A central liver lesion could not be resected due to its vessel proximity.\nSurgical pathology confirmed a mixed histology with differentiation of both, acinar cell carcinoma and ductal adenocarcinoma. Some morphologic features of the primary liver biopsy also resembled an embryonic tumor, but the pathognomonic squamoid differentiation of pancreatoblastoma was missing. One lymph node metastasis adjacent to the hepatic artery was found showing ductal differentiation. No neuroendocrine differentiation was detectable. Some tumor regression due to the preceding neoadjuvant chemotherapy was observed (fig. ). Immunostaining was focally positive for AFP in accordance with the initially elevated AFP serum levels. A diagnosis of a mixed acinar cell carcinoma/ductal adenocarcinoma was retained.\nTumor regrowth in the liver was observed on positron emission tomography/computed tomography (PET/CT) scan already 1 month after the second surgery. No tumor growth was seen in the remnant pancreas after Whipple resection. After subsequent second-line chemotherapy with two cycles of ifosphamide, carboplatin and etoposide (ICE regimen), a partial remission of the liver lesions was documented.\nA living donor liver transplantation (right hemiliver) from his brother was performed in November 2010. Due to a severe bile leak with abscess formation and finally hepatic artery thrombosis, the graft had to be replaced with a cadaveric liver graft after 10 days. Afterwards, the patient achieved complete recovery and was disease free. Immunosuppression with prednisone and tacrolimus was initially established. The former was subsequently tapered within 3 months, and tacrolimus was changed to everolimus.\nIn April 2011, multiple new lung metastases were detected while no tumor relapse was seen in the abdomen. Therefore, in May 2011 a new chemotherapy treatment with oxaliplatin, irinotecan, leucovorin and 5-fluorouracil (FOLFIRINOX regimen) was started. The new treatment was tolerated well apart from neutropenia and thrombocytopenia up to grade 4, resulting in dose reductions of the applied compounds. After six biweekly cycles, PET/CT showed a complete metabolic and partial morphologic remission of all lung lesions (fig. ).\nDue to the excellent response to FOLFIRINOX, we decided to consolidate with tandem high-dose chemotherapy using carboplatin, etoposide and paclitaxel as conditioning regimen with subsequent autologous stem cell transplantation (ASCT). Hematopoietic progenitor cells were successfully mobilized with filgrastim, and high-dose chemotherapy was performed in November 2011 and February 2012. Due to transiently elevated liver enzymes after the first high-dose treatment, etoposide was omitted in the second treatment to reduce the toxicity for the transplanted liver.\nIn August 2012, a progression of the pulmonary lesions was documented in a routine follow-up PET/CT. Treatment with FOLFIRINOX was once again initiated, resulting in a very good metabolic and morphologic remission after another six cycles until December 2012. Chemotherapy was continued for 3 additional months. While all lesions except one remained responsive to the treatment, the latter lesion was treated with stereotactic irradiation using 3 × 12 = 36 Gy.\nAs of today, the patient has a sustained metabolic remission of the known lung lesions and no new lesions developed with repeated use of FOLFIRINOX. He is currently in excellent general condition and has no limitations of his quality of life.