PMID- 29868484
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220317
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 8
DP  - 2018
TI  - Development of a Human Leukocyte Antigen Score to Predict Progression-Free 
      Survival in Head and Neck Squamous Cell Carcinoma Patients.
PG  - 168
LID - 10.3389/fonc.2018.00168 [doi]
LID - 168
AB  - BACKGROUND: In personalized medicine and treatment stratification of head and 
      neck squamous cell carcinoma (HNSCC), the heterogeneous genetic background of 
      patients is not considered. Human leukocyte antigen (HLA) alleles and HLA 
      haplotypes (HLA traits) are linked to development of HNSCC and affect 
      progression-free survival (PFS) of HNSCC patients but most head and neck 
      oncologists are not familiar with HLA typing. Hence, we developed an HLA-score 
      abstracting from complexity of HLA-typing results to facilitate potential use of 
      HLA-associated hazard ratios (HR) for prognostic stratification. METHODS: The HR 
      for PFS of 8 HLA traits shown to be independent predictors (Pi) of PFS in a test 
      cohort (TC) of 90 HNSCC patients were used to build the HLA-score based on the 
      natural logarithm (ln) of the Pi-associated HR. Crude ln-transformed HR of the 
      eight Pi, alleles B*13 (2), B*35 (1), B*51 (2), DQB1*06 (1), homozygous Cw (1), 
      homozygous DRB4 (2), and haplotypes A*01/B*08 (-6) and B*08/C*07 (4), were summed 
      up to yield the individual patient's HLA-score. Receiver operating characteristic 
      (ROC) and Kaplan-Meier curves were used to proof the suitability of the HLA-score 
      as prognostic marker for PFS. An independent validation cohort (iVC) of 32 
      patients treated in the larynx-organ preservation trial DeLOS-II was utilized for 
      validation. RESULTS: The individual HLA-scores (range -2 to 6) in TC classified 
      HNSCC patients regarding PFS. ROC analysis (area under the curve = 0.750, 95% CI 
      0.665-0.836; P = 0.0000034) demonstrated an optimum cutoff for the HLA-score at 
      0.5 (97.9% sensitivity, 34.7% specificity), and 70/90 patients in TC with 
      HLA-score > 0 had significant reduced PFS (P = 0.001). Applying the same 
      classifier (HLA-score > 0) confirmed these findings in the iVC revealing reduced 
      PFS of 25/32 patients (P = 0.040). CONCLUSION: HLA traits constitute critical Pi. 
      Considering the HLA-score may potentially facilitate the use of genetic 
      information from HLA typing for prognostic stratification, e.g., within clinical 
      trials.
FAU - Wichmann, Gunnar
AU  - Wichmann G
AD  - Clinic for Otorhinolaryngology, Head and Neck Surgery, University Hospital 
      Leipzig, Leipzig, Germany.
AD  - LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, 
      Leipzig, Germany.
FAU - Lehmann, Claudia
AU  - Lehmann C
AD  - Institute for Transfusion Medicine, University Hospital Leipzig, Leipzig, 
      Germany.
FAU - Herchenhahn, Cindy
AU  - Herchenhahn C
AD  - Clinic for Otorhinolaryngology, Head and Neck Surgery, University Hospital 
      Leipzig, Leipzig, Germany.
AD  - Clinic for Anesthesiology and Intensive Care, University Hospital Leipzig, 
      Leipzig, Germany.
FAU - Kolb, Marlen
AU  - Kolb M
AD  - Clinic for Otorhinolaryngology, Head and Neck Surgery, University Hospital 
      Leipzig, Leipzig, Germany.
FAU - Hofer, Mathias
AU  - Hofer M
AD  - Clinic for Otorhinolaryngology, Head and Neck Surgery, University Hospital 
      Leipzig, Leipzig, Germany.
FAU - Wiegand, Susanne
AU  - Wiegand S
AD  - Clinic for Otorhinolaryngology, Head and Neck Surgery, University Hospital 
      Leipzig, Leipzig, Germany.
FAU - Dietz, Andreas
AU  - Dietz A
AD  - Clinic for Otorhinolaryngology, Head and Neck Surgery, University Hospital 
      Leipzig, Leipzig, Germany.
AD  - LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, 
      Leipzig, Germany.
LA  - eng
PT  - Journal Article
DEP - 20180517
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC5966661
OTO - NOTNLM
OT  - biomarker score
OT  - head and neck cancer
OT  - head and neck squamous cell carcinoma
OT  - human leukocyte antigen
OT  - human leukocyte antigen haplotype
OT  - independent predictor
OT  - larynx-organ preservation trial
OT  - progression-free survival
EDAT- 2018/06/06 06:00
MHDA- 2018/06/06 06:01
PMCR- 2018/01/01
CRDT- 2018/06/06 06:00
PHST- 2018/03/07 00:00 [received]
PHST- 2018/05/01 00:00 [accepted]
PHST- 2018/06/06 06:00 [entrez]
PHST- 2018/06/06 06:00 [pubmed]
PHST- 2018/06/06 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2018.00168 [doi]
PST - epublish
SO  - Front Oncol. 2018 May 17;8:168. doi: 10.3389/fonc.2018.00168. eCollection 2018.