584 Background: Approximately 30% of all breast cancers are characterized as triple-negative (TNBC). TNBC typically occurs in younger women and is associated with a poorer prognosis relative to other breast cancer subtypes. High levels of tumor-infiltrating lymphocytes (TILs) in residual disease after Neoadjuvant chemotherapy (NACT) have previously been shown to be associated with better prognosis in TNBC. In this work, we sought to evaluate the prognostic value of computationally derived measures of TIL spatial architecture in residual TNBC after NACT. Methods: H&E-stained samples from 92 patients (pts) with TNBC (41 died, 45 had disease recurrence) and residual disease after NACT were retrospectively collected from 2 sites: Instituto Nacional de Enfermedades Neoplásicas (S1) and University Hospitals (S2). 45 pts (16 deaths, 23 recurrences) from S1 formed the training set and 47 pts (25 deaths, 22 recurrences) from S2 formed the independent validation cohort. Samples were digitized at 20x. Computerized algorithms automatically identified 2 types of nuclei (TILs and non-TILs) and built clusters for each nuclei type based on cell proximity. The spatial arrangement of these clusters was then quantified using network graph metrics. The top 5 features, determined by least absolute shrinkage and selection operator, were used to train a Cox regression model that assigned a risk of death and recurrence to each patient on the training set. The percentile 33 risk score was used as a threshold for stratifying pts on the validation set as either low or high risk. For comparison, we also employed a model based on TIL density alone. Survival analysis was used to evaluate the performance of both approaches on disease-free survival (DFS) and overall survival (OS). Results: Pts in S2 (n=47) identified as “high risk” by the model based on spatial architecture of residual TILs had a significantly shorter survival time. The median OS for pts at high risk was 25 months vs. 55 months for low-risk pts. The median DFS for pts at high risk was 32 months vs 51 months for low-risk pts. Univariable analysis showed this model was prognostic for both OS (Hazard Ratio (HR) = 2.57, 95% Confidence Interval (CI): 1.07-6.16, p=0.03) and DFS (HR=2.38, CI: 1.01-5.62, p=0.04). In contrast, the model based on TIL density was not prognostic for OS (HR=1.24, CI: 0.33-4.63, p=0.73) nor DFS (HR=1.19, CI: 0.32-4.34, p=0.78). Conclusions: A computerized image analysis model based on measurements of spatial arrangement of residual TILs and surrounding cells was found to be prognostic in TNBC pts who received NACT. This method appears to be more prognostic than TIL density alone. Additional multisite validation and multivariable analysis is needed to further establish the independent prognostic utility of TIL based image biomarkers in the post-NACT TNBC.
e16080 Background: Role of tumor-infiltrating lymphocytes (TIL) over clinicopathological features including Mismatch Repair (MMR), HER2 status, Epstein Barr Virus (EBV) and Helicobacter pylori (HP) infection is not well understood in gastric cancer (GC). Methods: TIL level and HP infection was also evaluated in H&E from 503 Peruvian GC patients who underwent surgery. Density of CD3+ T cells, CD8+ cytotoxic T cells, CD163 M2 macrophages, as well as MMR and HER2 status were determined by immunohistochemistry. HP and EBV infection was also detected by qPCR in a 234 cases subset. Results: Median age was 62 years and 50.1% were female, most tumors were grade 3 (59.1%), intestinal subtype (44.8%) and stage III (59.8%). MMR loss was found in 29.4% and HER2+ in 4.7%. HP+ was detected by H&E in 55.7% and by qPCR in 63.7%. EBV+ by qPCR was found in 20.5% and co-infection along with HP in 9.4% (22/234). Stage (p < 0.001), intestinal histology (IH) (p = 0.019), grade (p = 0.006) and lymphovascular invasion (p < 0.001) were associated with longer survival. Median TIL was higher in invasive border (IB) and stromal (ST) than intratumoral (IT) compartment but there were significantly correlated (p < 0.001). High IT TIL was associated with absence of HP H&E (p = 0.009). High ST TIL was associated with older age (p < 0.001), IH (p < 0.001), grade 1 (p = 0.009), lower stage (p = 002), MMR loss (p = 0.019) and EBV+ (p = 0.001). Density of CD3 and CD8 were significantly correlated in IT and ST compartments (p < 0.001). High CD3 density in IT compartment was associated with grade 3 (p = 0.001) and HP- (p = 0.02), and in ST was associated with IH (p = 0.005), grade 1- 2 (p = 0.002) and MMR loss (p = 0.04). High IT CD8 was associated with HER2- (p = 0.016), HP- (p = 0.014) and EBV+ (p = 0.012). High ST CD8/CD3 ratio was associated with diffuse histology (p = 0.034), grade 3 (p = 0.013), more advanced stage (p = 0.022) and recurrence (p = 0.014). High ratio of IT CD8/CD3 was associated with MMR loss (p = 0.007). High ST TIL was associated with longer DFS (p = 0.007). Lower ratio of CD8/CD3 was associated with longer OS (p = 0.024) and DFS (p = 0.02). Conclusions: TIL levels and infiltrating immune subpopulations differs by clinicopathological features in GC including MMR loss, HER2 expression EBV and HP infection. ST CD8/CD3 was associated with recurrence and shorter DFS.
e18849 Background: Malignant melanoma in Latin American (LATAM) population has aggressive features as higher rates of Acral lentiginous (ALM) subtype and shorter survival. Immunotherapy has improved prognosis among patients with cutaneous melanoma; however, there is scarce reports of the effectiveness in LATAM population. We describe our experience with management and survival of Peruvian patients with advanced melanoma treated whit nivolumab. Methods: A retrospective study based on cases review evaluated the efficacy of nivolumab. Eligible patients were metastatic, recurrent or unresectable malignant melanoma undergoing treatment with nivolumab as first-line for at least 3 consecutive months between 2020 and February 2021 in two institutions (Instituto Nacional de Enfermedades Neoplasicas, Oncosalud). Clinical pathologic features and immune inflammatory blood markers (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic nutritional index (PNI)) were evaluated. Efficacy was measured as progression-free survival (PFS), objective response rate (ORR), Clinical benefit rate (CBR) and overall survival (OS). A p < 0.05 value (SPSS) will be considered for a significant difference. Results: 57 patients were analyzed; median age was 63 yo (range 34-83); 59.6% were female. 77.2% had a Zubrod 0-1. Regarding histology, 37% (n = 21) had acral subtype, 38% (n = 22) non-acral, 17% (n = 10) mucosal and 8% (n = 4) unknown primary (UP). 81.1% had negative BRAF mutation status, and the median lactate dehydrogenase (LDH) level was 257 U/L (130-1281). 63.2% had visceral metastasis, the most common site being lung (42%) and liver (9%). Central nervous system (CNS) metastases was reported in 5%. After a median follow-up was 25 months, the median OS reported was 51.43 months (95% CI, 14.23-88.62). Median OS was 28.93 for acral melanoma (95% CI, 14.66-43.19) and not reached for other subtypes. Median PFS was 7.93 months (95% CI, 2.49-13.36); 4.93, 14.73 and 5.26 months in patients with acral, non-acral and mucosal melanoma, respectively. A significant difference was founded in OS (p = 0.024) and PFS (p = 0.001) between acral and non-acral melanoma. ORR was reached in 28.1% of patients; 19%, 31.8% and 20% in acral, non-acral and mucosal subtype, respectively. However, global CBR was 64.9%, with the higher and lower rate for non-acral (81.82%) and mucosal melanoma (50%). The overall incidence of immune related adverse effects (irAEs) was 69.5%, the most common were skin reactions (14%), followed by asthenia (12%); not grade 3-4 AEs were reported. Regarding immune inflammatory blood markers, no association between PFS with NLR (p = 0.49), PLR (p = 0.3) and PNI (p = 0.71) were founded. Conclusions: Nivolumab showed efficacy in improving OS for patients with advanced melanoma, however ALM had shorter OS and PFS. No prognostic immune blood markers were reported. New biomarkers are necessary, especially in acral melanoma.
BACKGROUND: Gastric cancer (GC) is the second most common cancer and first leading cause of cancer-related deaths in Peru. Infection by Helicobacter pylori (HP) and Epstein-Barr virus (EBV) are accepted carcinogenic and infection is widely spread in the Peruvian population. The aims of this study were to evaluate HP and EBV-associated GC (EBVaCG), to assess the prevalence rate and to define the characteristics of Peruvian patients. METHODS: GC samples were prospectively collected from patients who underwent gastroscopy or surgical resection with no preoperative treatment at INEN between 2015 and 2017. Tumor tissue (T), proximal healthy tissue (P) and distal healthy tissue (D) samples were assessed for HP and EBV by quantitative PCR (qPCR) using specific primers. HP and EBV status were analyzed along with clinicopathologic parameters of the tumor. Kaplan-Meier estimation curves overall survival (OS) was applied. Comparison between qPCR detection and current standard methods of detection was also performed. All tests were two sided, and a p≤0.05 was considered statistically significant. RESULTS: A total of 150 patients were studied with a mean age 65 years and predominance of males (51.3%). Intestinal-mixed histological subtype rate was 72.5% in cases. Most frequent clinical stage was III-IV (74.6%). HP+ patients were determinate with at least one ureA/hspA gene result and EBV+ patients were divided in high viral load (>100copy/μl) and low viral load (<100copy/μl) groups. Results found HP in 87.3% (n=131/150) and EBV in 10% (n=15/150) of the population. Cases and HP concentration were higher in D (ureA: 62.8%, [703.58±245.47pg]; hspA: 73.8%, [42.77±10.17pg]) than P (ureA: 59.0%, [539.69±121.32pg]; hspA: 71.0%, [31.90±8.64pg]) and T (ureA: 49.7%, [296.32±164.98pg]; hspA: 70.5%, [4.6±1.33pg]) (p<.001). High viral load EBV was found in 40% (n=6/15) of cases. Co-infection detection rate was 7.3% (n=11/150). Correlation between qPCR and H&E evaluation of HP was found in only 72.9% (n=19/57) of cases without evidence of HP (p<.001) and no detectable expression of EBV was found by EBER in qPCR positive cases (n= 15). Cases were defined in 4 groups: HP+EBV+ (n=9), HP+EBV- (n=98), HP-EBV+ (n=6), and HP-EBV- (n=37). Results showed median age (67, 66, 67 and 66), most frequent III-IV clinical stage (75%, 69.5%, 72.7% and 62.1%), histologic grade found was GII (50%, 28.8%, 50% and 43.3%) and intestinal-mixed histological subtype (66.6%, 56.6%, 100% and 62.1%) in four groups respectively. EBVaGC was associated to OS (38.3% vs 72.3%) at 1 year, p=0.033). Based on a mean follow-up of 24 months, the 1-year survival was lower in EBV+ [45.5% (HP+ EBV+) and 25% (HP- EBV+)] than in EBV- [73.1% (HP+ EBV-) and 61.5% (HP- EBV-)] groups. CONCLUSION: HP infection is frequent in Peruvian CG patients. Presence of HP and EBV infection evaluated by qPCR define 4 groups with different features and survival. Study supported by CIENCIACTIVA-CONCYTEC, under the contract #196-2015-FONDECYT. Citation Format: Carolina Belmar López, Miluska Castillo Garcia, Carlos A. Castañeda Altamirano, Luis F. Barreda Bolaños, Daniel Valdivia Leonardo, Eduardo Payet Meza, Valeria Villegas Bernaola, Jais Nieves Prado, Joselyn R. Sanchez Sifuentes, Luis A. Bernabé Monsalve, Manuel A. Chumpitaz La Rosa Sanchez, Omar Mejía Dionisio, Ivan Chavez Passiuri. HP and EBVaGC in Peruvian patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4210.
e12654 Background: The response after neoadjuvant chemotherapy (NAC) is the main prognostic factor in breast cancer (BC), likewise, malnutrition, anemia and systemic inflammation have also been associated to prognosis in breast cancer. We evaluated the association between pathological response (PR) and tumor infiltrating lymphocytes (TILs) post NAC with nutritional predictors as body mass index (BMI), prognostic nutritional index (PNI), anemia and neutrophil/lymphocyte index (N/L). Methods: This is a retrospective analysis of women diagnosed with BC between 2006 to 2017 at Instituto Nacional de Enfermedades (INEN) who received NAC. Pathological response was classified through residual cancer burden (RCB) and TILs post NAC which were prospectively evaluated by a pathologist. Clinical and pathological features as well as survival status were obtained from patient files. Results: We identified 439 women with BC who received NAC. Median age was 49 years, histological grade 3 was found in 245 patients (55.8%) and stage IIIB was the most frequent at diagnosis with 257 patients (58.5%). Luminal B subtype was the most frequent (43.7%). Rate of pCR was 10.5% and median TILs post NAC was 20%. About nutritional predictors, we use the median as a cutoff to discriminate between high and low values, for BMI was 27.5, for PNI was 56, for hemoglobin was 13.2 and for NLR was 1.84. There was no association for TILs post NAC with BMI (p = 0.38), PNI (p = 0.057) and hemoglobin (p = 0.43). We found a positive association between ILN and TILs post NAC (p = 0.001). On the other hand, we don’t found association for RCB with BMI (p = 0.45), PNI (p = 0.641), ILN (p = 0.2) and hemoglobin (p = 0.15). In the multivariate analysis, only RCB was an independent predictor for DFS (95 % CI, 87-100.5; p = 0.00001) and OS (95 % CI, 101.8-114.1; p = 0.00001). There was no association between BMI, PNI, ILN and anemia with OS and DFS. For the TILs post NAC there was a tendency to association with DFS (p = 0.07) and OS (p = 0.07). Conclusions: There are association between neutrophil/lymphocyte index with TILs after NAC. There was no association between nutritional and systemic predictors with long-term outcomes. The pathologic response is a biomarker for predicting the long-term outcomes of breast cancer patients.
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