Clinical and molecular features of adenosquamous pancreatic cancer (ASQ): A distinct histological subtype.
Authors: Jakubowski Christopher , Lim Su Jin , Pellatt Andrew , Wang Hao , Burkhart Richard A. , Thompson Elizabeth , Azad Nilofer Saba 
Published: January 2021

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Background: Adenosquamous pancreatic cancers (ASQ) constitute 1-5% of all pancreatic cancers. The clinical and molecular understanding of this aggressive variant, along with potential differential response to systemic therapies, is an understudied yet important topic. Methods: After obtaining Institutional Review Board approvals, the Johns Hopkins cancer registry and electronic medical record was interrogated for histopathological and clinical characteristics of ASQ. Archived pathological slides were re-examined to quantify the squamous component, response to neoadjuvant therapy and immune infiltrate. Results: Of 8,908 patients from 2003 to 2018, a total of 155 had histology consistent with ASQ. 52% presented with resectable disease, 12% with borderline resectable, 12% with locally advanced, 17% with metastatic, and 8% of cases had an unknown presentation status. Primary FNA diagnosis was available for 103 patients and 57% (n = 59) reported squamous findings on FNA. 53 patients received radiation therapy (19 neoadjuvant, 22 adjuvant, 15 palliative). Systemic therapy was received by 104 patients (32 neoadjuvant, 52 adjuvant, 67 palliative therapy for advanced/metastatic disease). The most common neoadjuvant regimens used were FOLFIRINOX (n = 9) and gemcitabine/nab-paclitaxel (n = 7). Reported responses in the neoadjuvant setting (n = 26) included 10 with stable disease (SD), 11 partial response (PR) and 5 progressive disease (PD). The most common regimens used in the first line advanced setting were FOLFIRINOX (n = 18), gemcitabine/nab-paclitaxel (n = 9), and gemcitabine (n = 8). Of 55 responses recorded there were 13 SD, 15 PR, 25 PD and 2 complete responses (CR). Of the patients who received first line therapy, 54% (n = 36), 15% (n = 10) and 6% (n = 4) went on to receive second, third or fourth line therapy, respectively. 118 patients (76.13%) had a reported date of death. Of the 98 patients who received definitive surgical resection the median recurrence free survival (mRFS) and overall survival (mOS) was 7.36 and 14.17 months, respectively. Of the 44 patients that presented with de novo unresectable or metastatic disease, mOS was 7.53 months. The mOS of advanced disease patients from the time of receipt of first line palliative chemotherapy was 8.45 months. Molecular panels revealed mutation frequencies of common somatic and DNA repair genes in similar frequency to pancreatic adenocarcinoma. The mean tumor mutation burden of 18 patients was 4.7 with a max of 27. Of 27 patients who received MMR/MSI testing 100% were pMMR/MSS. Conclusions: This is one of the largest single center series of ASQ patients reported and describes unique findings related to neoadjuvant and advanced disease treatment experience. Overall this study confirms the continued poor survival and poor response to standard regimens in this disease suggesting we should consider alternative treatment paradigms.