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Oral Oncol. 2018 Jun;81:1-9. doi: 10.1016/j.oraloncology.2018.04.007. Epub 2018 Apr 10.

Integrated genomic characterization of oral carcinomas in post-hematopoietic stem cell transplantation survivors.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA. Electronic address: glenn_hanna@dfci.harvard.edu.
2
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.
3
Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, USA.
4
Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, USA; Department of Pathology, Brigham and Women's Hospital, Boston, USA.
5
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, USA.
6
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Broad Institute, Massachusetts Institute of Technology, Cambridge, USA.
7
Department of Head and Neck Surgical Oncology, Dana-Farber Cancer Institute, Brigham & Women's Hospital, Boston, USA.

Abstract

OBJECTIVES:

Secondary oral squamous cell carcinoma (OSCC) is a late complication in allogeneic hematopoietic stem cell transplantation (HSCT) patients, but little is known about long-term outcomes and prognostication. Additionally, molecular alterations and immunologic insights unique to this disease remain largely unexplored.

METHODS:

We present a cohort of 31 patients with post-HSCT OSCC and reported on clinicopathologic predictors of survival. Whole-exome sequencing was performed on 6 (19%) matched pairs of peripheral blood (post-conditioning, pre-HSCT) and tumor samples. The entire cohort had archival tumor available for immunoprofiling with PD-1/L1 immunohistochemistry.

RESULTS:

Five-year overall survival (OS) was 57% (95% CI: 46.1-69.8) with a median disease-free survival (DFS) of 13.3 months. Advanced initial staging, a buccal or oral tongue subsite, chronic oral graft-versus-host disease (GVHD) and smoking all negatively impacted survival. High tumor mutational burden (TMB) (median 11.3 vs. 5.0) and unique mutational signatures were noted between unrelated and related donor groups - with a strong correlation between infiltrating PD-1+ lymphocytes and TMB (R = 0.98, p < 0.01). Some differences were observed when comparing commonly mutated genes among our cohort and TCGA, with a predominance of TP53 events.

CONCLUSION:

Survival outcomes appear similar in HSCT survivors with OSCC compared with non-HSCT OSCC populations. We identified somatic alterations in genes with therapeutic potential unique to this subpopulation of oral cancers.

KEYWORDS:

Bone marrow transplantation; Genomics; Immunology; Oral cancer; Outcomes

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