BackgroundFor early‐stage oral squamous cell carcinoma (OSCC), there is no existing risk‐stratification modality beyond conventional TNM staging system to identify patients at high risk for cancer‐specific mortality.MethodsA total of 568 early‐stage OSCC patients who had surgery only and also with available 5‐year clinical outcomes data were identified. Signature microRNAs (miRNAs) were discovered using deep sequencing analysis and validated by qRT‐PCR. The final 5‐plex prognostic marker panel was utilized to generate a cancer‐specific mortality risk score using the multivariate Cox regression analyses. The prognostic markers were validated in the internal and external validation cohorts.ResultsThe risk score from the 5‐plex marker panel consisting of miRNAs‐127‐3p, 4736, 655‐3p, TNM stage and histologic grading stratified patients into four risk categories. Compared to the low‐risk group, the high‐risk group had 23‐fold increased mortality risk (hazard ratio 23, 95% confidence interval 13‐42), with a median time‐to‐recurrence of 6 months and time‐to‐death of 11 months (vs >60 months for each among low‐risk patient; p < .001).ConclusionThe miRNA‐based 5‐plex marker panel driven mortality risk score formula provides clinically practical and reliable measures to assess the prognosis of patients assigned to an early‐stage OSCC.

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e14528 Background: Immunotherapy has revolutionized cancer treatment by harnessing the power of the patient’s immune system to fight the disease. While immunotherapies have become increasingly effective, the proportion of patients not responding to immunotherapy ranges between only 20-50%. New breakthroughs in the understanding of the tumor immune biology have led to the development of new, more effective therapies; however, these breakthroughs often hinge on tools that can elucidate the role and abundance of individual components of the patient’s immune system in the tumor microenvironment. Methods: This poster describes the performance of 26 gene enrichment signatures that allow for the measurement of the relative abundance of 23 individual immune and stromal cells in the tumor environment, in addition to providing composite inflammation, stroma and tumor microenvironment scores. These Research Use Only (RUO) signatures are based on gene expression profiling (GEP) data for 1,392 genes implicated in tumor-immune interaction generated using the HTG EdgeSeq Precision Immuno-Oncology Panel (RUO). The signatures were developed and validated using GEP data from 1,073 colorectal, gastric and ovarian cancer formalin-fixed paraffin-embedded (FFPE) tissue specimens. Results: The signature accuracy was independently verified by spiking known numbers of representative immune and stromal cells into an FFPE tissue lysate; the signature outputs were highly correlated to the number of immune and stromal cells present in the sample, with Pearson correlation coefficients ranging from 0.71 to 0.98. In addition, the outputs of some of the signatures were compared to multiple commonly used immunohistochemistry markers of immune cells in 61 non-small-cell lung carcinoma FFPE samples. The results showed a high degree of correlation, with Pearson correlation coefficients of 0.77 and 0.81 for CD4 and CD8, respectively. Conclusions: These immunophenotyping signatures provide a suite of robust tools for the characterization of the tumor microenvironment in order to better understand the tumor immune biology and mechanisms of resistance to immunotherapy. The signature scores can typically be generated from a single section of FFPE tissue using HTG’s extraction-free GEP technology and a fully automated bioinformatic pipeline available in the HTG EdgeSeq Reveal software.

The NCCN guidelines provide prognostic guidance and treatment options for patients (pts) with localized prostate cancer. Men with poor prognosis are considered high risk (HR) (clinical stage !T3a or PSA >20 ng/mL or Gleason (Gl) !8) and men with locally advanced disease (T3b-T4) or the worst prognosis (!2 HR factors) are considered very high risk (VHR). The 2015 guidelines expanded VHR by adding 2 new risk factors (RF) (primary Gl 5 or !5 cores with Gl 8-10) that better select pts at risk for poor outcomes after surgery. We reviewed treatment outcomes and patterns of failure in a cohort of HR pts to determine if the original or revised NCCN VHR groups offer prognostic information for pts treated uniformly with contemporary radiation therapy (RT) and androgen deprivation therapy (ADT). Materials/Methods: Two hundred three HR pts were extracted from an IRB approved database treated with RT from November 2001 to March 2012. Treatment was conformal RT to the prostate (78-82 Gy), pelvic lymph nodes (46-50 Gy), and ADT (6 months-2years). The HR cohort was divided into separate HR/VHR groupings based on the 2014 and 2015 NCCN definitions of VHR and since inclusion of !2 HR factors is optional we have 4 groups: VHR 2014 !T3b or AE !2 HR factors; and VHR 2015 !T3b or primary Gl 5 or !5 cores with Gl 8-10 or AE !2 HR factors. Outcomes for each of the 4 HR/VHR groups were compared. Disease-free survival (DFS) included metastatic, nodal, local, and biochemical failures (Phoenix definition). Kaplan Meyer (KM) method was used to determine probability of survival. Cox univariate and multivariate regression analysis were used to determine significant covariates. P values .05 were considered significant. Results: The 2015 NCCN revision increased the number of RFs considered for inclusion into the VHR group from 1-4. Pts were shifted from HR to VHR as follows: 2014 AE !2 HR factors (HR166:VHR37, HR131:VHR72) respectively and 2015 AE !2 HR factors (HR100:VHR103, HR65:VHR138) respectively. The percentage of VHR pts increased from 18% to 68% and the percentage of HR pts decreased from 82% to 32%. For all 203 pts: Median follow-up was 50 months; 30 of 203 (15%) experienced failure; median time to failure was 30 months; KM estimate of 4-year DFS was 87% (95% CI: 82%-92%) with no significant differences between the HR and vHR groups (log-rank PZns). On multivariate analysis the factors defining the VHR cohort defined by 2014 or 2015 criteria were not significant and only PSA !40 ng/mL was significant HR: 4.28, (95% CI: 1.98-9.25, P<.001, 4-year DFS 91% versus 68% PSA < 40 ng/mL: PSA ! 40 ng/mL). Conclusion: In this cohort treated with high-dose conformal RT and ADT, reclassification of pts into VHR groups using 2014 or 2015 criteria or upstaging pts with !2 HR criteria had no impact on treatment outcomes. Only PSA !40 ng/mL was associated with poor outcome on multivariate analysis. Further study and longer follow-up is required to validate these findings.

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