Citations

3579 Background: Tumor infiltrating lymphocytes (TIL) indicate a host immune response that may influence survival. Immunoscore was developed using CD3+ and CD8+density and location in primary CC pts with pooled stages, varying treatment and follow-up. We determined if individual immune markers and/or Immunoscore are prognostic in resected stage III CC pts (N=600). Methods: CD3+ and CD8+ T-cell or CD20+ B lymphocyte density in central tumor (CT) and invasive margin (IM) was evaluated by immunostaining and quantified by image analysis. Immunoscore was calculated on a scale of I0 to I4 with high densities of CD3+ and CD8+in both CT and IM scored as I4; low densities scored as I0. Associations with disease-free survival (DFS) were evaluated by multivariable Cox regression adjusting for covariates. Results: Data for CD3+, CD8+ and CD20+ were generated (N=595). Higher density of CD3+ CT, CD3+ IM and CD8+ IM were associated with longer DFS adjusting for covariates (Table). CD3+ IM had the strongest association with DFS, and was stronger in left-sided (HRadj.=0.81, 95% CI, 0.70-0.94, padj.= 0.0049) vs right-sided (HRadj.=0.93, 95% CI, 0.85-1.0 padj.=0.52) tumors (pinteraction=0.039). Higher density of CD3+ IM was associated with older age (p=0.034), T1/2 (p<.0001), N1 (p=0.017), right-sided (p=0.013), high TILs (p=0.0008), and deficient MMR (p=0.0003). Using a prior Immunoscore risk stratification, higher scores were associated with better DFS (HR.=0.62, CI, 0.44-0.87, p=0.006) (Table). Conclusions: Densities of CD3+ and CD8+, especially at IM, are individually prognostic in FOLFOX-treated pts. Association of CD3+IM with prognosis differed by primary CC site. Immunoscore was strongly prognostic, and this result provides validation in a clinical trial cohort. [Table: see text]

3535 Background: CRC is known to be a heterogeneous disease. This study quantifies within pt heterogeneity in early lesion change rate (LCR) in the era of targeted agents compared to chemo alone and its potential impact on survival. Methods: Pts with 2-10 lesions measured at baseline were included. For each lesion, the early LCR was defined as the change in size (shrinking or growing) from baseline to 12 weeks on treatment. Within pt heterogeneity in early LCR among lesions was estimated by standard deviation (STD). A larger value of STD indicates larger variation of LCR per pt. Stratified multivariate Cox models were used to assess the associations between LCR STD with overall survival (OS). Adjusted hazard ratios (HRadj) and 95% confidence intervals (CIs) are reported. Results: Data were available on 9,092 mCRC pts (median age 61; 60% male, 55% ECOG PS 0; 61% 2+ metastatic sites) enrolled in 16 1st-line randomized trials, with 44%, 42%, and 10% of pts received chemo alone, + a VEGF inhibitor (VEGFi) or an EGFR inhibitor (EGFRi), respectively. LCR heterogeneity is the highest among pts received EGFRi but lowest among pts received VEGFi (Table). Overall, higher heterogeneity is associated with worst OS (HRadj1.22, 95% CI (1.16, 1.27)). The effect is most pronounced in pts received VEGFi (interaction p=0.0012). Conclusions: There was heterogeneity observed in lesion size changes within pts. Its magnitude varies across treatment approaches, and was associated with poor survival. This preliminary result reveals the great potentials to define novel response endpoint and refine treatment decision-making by incorporating heterogeneities in lesion changes. [Table: see text]

3516 Background: Epidemiological data suggest a protective effect of vitamin D on CC risk. However, association of serum vitamin D level with clinical outcome in pts with surgically resected CC remains unknown. We analyzed total circulating 25-hydroxyvitamin D [25(OH)D)] with clinical outcome in pts with resected stage III CC treated with FOLFOX +/- cetuximab in a phase III trial. Methods: Association of pre-treatment level of plasma 25(OH)D with disease-free survival (DFS) and time-to-recurrence (TTR) was analyzed with 25(OH)D as a continuous variable by a relative risk model with splines and as a binary variable (vitamin D deficient [<30 ng/mL]) using multivariable Cox regression. Results: Overall, 49% (291/600) of pts were vitamin D deficient. Prevalence of vitamin D deficiency was significantly higher in women vs men (52% vs. 48%, p=0.030) and in blacks vs whites (74% vs. 45%, p=0.0003). The continuous 25(OH)D level and pt sex were associated by the interaction test (pinteraction=0.044). There were no statistically significant associations with DFS/TTR for either continuous 25(OH)D level (DFS, p=0.22; TTR, p=0.26) nor for vitamin D deficiency (DFS, adjusted hazard ratio [HRadj]=1.01, 95% CI, 0.74-1.38; padj=0.94; TTR, HRadj=1.00; CI, 0.72-1.38; padj=0.99. A comparison of the highest vs lowest tertile showed a significant association between the highest 25(OH)D level and better outcomes in men (DFS, HRadj.=0.18, CI, 0.04-0.76, padj=0.020; TTR, HRadj.=0.12, CI, 0.02-0.64, padj=0.014), but not in women (DFS, pinteraction=0.039; TTR, pinteraction=0.033). Conclusions: Nearly one-half of pts in the clinical trial cohort were vitamin D deficient with lowest 25(OH)D levels found in women and blacks. While vitamin D deficiency was not associated with adverse outcome, high levels of vitamin D in men, but not women, were associated with longer survival. Support: U10CA180821, U10CA180882, U10CA180820, U10CA180863, U10CA180888, U10CA077202, CCSRI 021039. ClinicalTrials.gov Identifier: NCT00079274.

LBA1 The full, final text of this abstract will be available at abstracts.asco.org at 7:30 AM (EDT) on Sunday, June 4, 2017, and in the Annual Meeting Proceedings online supplement to the June 20, 2017, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.