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. 2019 Jan 10:11:599-609.
doi: 10.2147/CMAR.S185352. eCollection 2019.

Genetic analysis of subsequent second primary malignant neoplasms in long-term pancreatic cancer survivors suggests new potential hereditary genetic alterations

Martin Lovecek  1 , Marketa Janatova  2 , Pavel Skalicky  1 , Tomas Zemanek  3 , Roman Havlik  1 , Jiri Ehrmann  4 , Ondrej Strouhal  3 , Petra Zemankova  2 , Klara Lhotova  2 , Marianna Borecka  2 , Jana Soukupova  2 , Hana Svebisova  3 , Pavel Soucek  5 , Viktor Hlavac  5 , Zdenek Kleibl  2 , Cestmir Neoral  1 , Bohuslav Melichar  3 , Beatrice Mohelnikova-Duchonova  3
Affiliations

Genetic analysis of subsequent second primary malignant neoplasms in long-term pancreatic cancer survivors suggests new potential hereditary genetic alterations

Martin Lovecek et al. Cancer Manag Res. .

Abstract

Background: The principal aim of this report was to study second primary malignant neoplasms (SMNs) in long-term survivors of pancreatic ductal adenocarcinoma (PDAC) with regard to the germline genetic background.

Patients and methods: A total of 118 PDAC patients after a curative-intent surgery who were treated between 2006 and 2011 were analyzed. Of the 22 patients surviving for >5 years, six went on to develop SMNs. A genetic analysis of 219 hereditary cancer-predisposition and candidate genes was performed by targeted next-generation sequencing in germline DNA from 20 of these patients.

Results: Of all the radically resected PDAC patients, six patients went on to subsequently develop SMNs, which accounted for 27% of the long-term survivors. The median time to diagnosis of SMNs, which included two cases of rectal cancer, and one case each of prostate cancer, malignant melanoma, breast cancer, and urinary bladder cancer, was 52.5 months. At the time of analysis, none of these patients had died as a result of PDAC progression. We identified four carriers of germline pathogenic mutations in 20 analyzed long-term survivors. One carrier of the CHEK2 mutation was found among four analyzed patients who developed SMNs. Of the remaining 16 long-term PDAC survivors, 3 patients (19%) carried germline mutation(s) in the MLH1+ ATM, CHEK2, and RAD51D gene, respectively.

Conclusion: This retrospective analysis indicates that SMNs in PDAC survivors are an important clinical problem and may be more common than has been acknowledged to be the case. In patients with good performance status, surgical therapy should be considered, as the SMNs often have a favorable prognosis.

Keywords: hereditary cancer genes; long-term survivors; pancreatic ductal adenocarcinoma; second primary neoplasms; subsequent malignant neoplasm; surgical treatment.

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Conflict of interest statement

Disclosure A grant from Palacky University was awarded to TZ (IGA_LF_2018_010), Charles University Projects (UNCE/MED/006) was awarded to PSo, and PROGRES grants (Q28/LF1 and SVV 260367) were awarded to PZ, KL, and MB. The authors report no other conflicts of interest in this work.

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