Independent Predictor Of DFS Research Articles

Prognostic relevance of preoperative CA 19-9 values in stage III rectal adenocarcinoma: retrospective analysis and clinical implications

<p><strong>Aim</strong> <br />To investigate prognostic significance of preoperative levels of the Carbohydrate anti-gen 19-9 (CA 19-9) in patients with stage III rectal adenocarcinoma who underwent a treatment at the Clinical Centre of the University of Sarajevo.<br /><strong>Methods</strong> <br />A retrospective cohort study included 84 patients who underwent radical anterior rectal resection due to grade III rectal adenocarcinoma, followed by adjuvant chemotherapy according to the FOLFOX protocol (Oxaliplatin, Leucovorin, 5-Fluorouracil (5-FU)). The patients were divided into two groups according to CA 19-9 values (≥27 U/mL and <27 U/mL, respectively). <br /><strong>Results</strong> <br />High pre-operative CA 19-9 values predicted an increased probability of postoperative metastases, especially liver, lung and abdominopelvic metastases, as well as three-year disease-free survival (3Y-DFS) and three-year overall survival (3Y-OS). The 3Y-DFS rate for patients with high CA 19-9 was 64.5%, while for those with low CA 19-9 it was 87.2%. The 3Y-OS rate for patients with high CA 19-9 was 89.8%, while for those with low CA 19-9 it was 65.7%. Univariate and multivariate regression analysis confirmed that a high level of CA 19-9 is an independent predictor for DFS and OS shorter than three years.<br /><strong>Conclusion</strong> Pre-operatively elevated values of CA 19-9 in rectal adenocarcinoma have a significant role in predicting the outcome in patients with stage III rectal adenocarcinoma.</p>

Relevance of shrinkage versus fragmented response patterns in rectal cancer.

Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome. The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three-step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II-IV, 78% versus 35%; P < 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19-3.50, P = 0.008) and disease-free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23-5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS. The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response.

Artificial intelligence-based reticulin proportionate area - anovel histological outcome predictor in hepatocellular carcinoma.

Reticulin stain is used routinely in the histological evaluation of hepatocellular carcinoma (HCC). The goal of this study was to assess whether the histological reticulin proportionate area (RPA) in HCCs predicts tumour-related outcomes. We developed and validated a supervised artificial intelligence (AI) model that utilises a cloud-based, deep-learning AI platform (Aiforia Technologies, Helsinki, Finland) to specifically recognise and quantify the reticulin framework in normal livers and HCCs using routine reticulin staining. We applied this reticulin AI model to a cohort of consecutive HCC cases from patients undergoing curative resection between 2005 and 2015. A total of 101 HCC resections were included (median age = 68 years, 64 males, median follow-up time = 49.9 months). AI model RPA reduction of > 50% (compared to normal liver tissue) was predictive of metastasis [hazard ratio (HR) = 3.76, P = 0.004, disease-free survival (DFS, HR = 2.48, P < 0.001) and overall survival (OS), HR = 2.80, P = 0.001]. In a Cox regression model, which included clinical and pathological variables, RPA decrease was an independent predictor of DFS and OS and the only independent predictor of metastasis. Similar results were found in the moderately differentiated HCC subgroup (WHO grade 2), in which reticulin quantitative analysis was an independent predictor of metastasis, DFS and OS. Our data indicate that decreased RPA is a strong predictor of various HCC-related outcomes, including within the moderately differentiated subgroup. Reticulin, therefore, may represent a novel and important prognostic HCC marker, to be further explored and validated.

Abstract P4-06-06: Neoadjuvant B27 protocol in Triple-Negative Breast Cancer: Evaluation response rate, pathological complete response rates,toxicity,and the prognosis of Adolescent and Young Adult (AYA) age group compared to older population

Abstract Background: Neoadjuvant chemotherapy (NACT) is the standard early-stage triple-negative breast cancer (TNBC) treatment. Achieving pathological complete response (pCR) is considered an essential prognostic factor with favorable long-term outcomes. Younger patients have with poorer prognosis in breast cancer. To date, few studies are comparing the prognosis of AYA and older women (≥40) with breast cancer subtypes, specifically Triple-negative breast cancer (TNBC), as AYAs had higher proportions of this subtype. Method: Retrospective review was performed on female patients who received NACT at a King Hussien Cancer Center from January 2014 to June 2020. Data were collected from patients’ electronic medical records. TNBC was histopathologically confirmed. Logistic regression analysis of predictors of pathologic complete response (pCR). Survival curves were estimated with the Kaplan-Meier method. Multivariate analysis for EFS was performed using Cox’s proportional hazards regression model, covariates included age at diagnosis (AYA vs. ≥40), tumor size, nodal status LVI and pCR Result: We analyzed 211 women with stage I-III TNBC, including 62 (29.4%) women aged 18 to 39 years (AYA) and 149 (70.6%) ≥40 years. 138 (68.3%) were node positive, and 71 (34.8%) were T3/4 disease. Median follow-up was 28.1 months, median number of ER visit during NAC is 1 (0-11), 23 (10.9 %) patients had admission during neoadjuvant chemotherapy, most commonly due to febrile neutropenia 13 (56.9%). 37 (17.5%) patients did not complete NAC, due to disease progression in 22 (10.4%), and toxicity in 15 (7.1%) patients. 195 (92.4%) patients had surgery, including 75 (35.5%) had breast-conserving surgery (BCS). 166 (76.3%) patients had objective response, and 64 (30.3%) had pCR. 170 (80.6%) received adjuvant radiotherapy, and 38 (18%) received adjuvant capecitabine. No significant differences between the AYA and the ≥40 group in terms of clinicopathological, toxicity, pCR rate, and the rate of BCS. In univariate analysis, the LVI, nodal status, pCR, and age group were significant predictors of DFS. In multivariate analysis, only PCR and age are the only independent predictor of DFS. The median DFS was worse in the AYA population 47.8 (31.21-64.39) months vs. NR in ≥40 (p-value 0.013). In patients who achieved pCR, the estimated 5-years DFS for the AYA group was 56.1% versus 86.8% for the ≥40 group, (p-value 0.71). In patients with residual disease, PFS for AYA was 34.2 (95%CI 11.5-57) months vs. 59.5 months in the ≥40 group, (p 0.009). Conclusion: Although there is no difference in pCR between the AYA age group patient treated with NACT for TNBC and the older age group, the DFS is significantly worse in the AYA than the ≥40 age group in patients with residual disease. As well, DFS is numerically worse in the AYA age vs. the ≥40 age group in patients who achieved pCR. Citation Format: Faris Tamimi, Baha’ Sharaf, Suhaib Khater, Suhaib Al-Sawajneh, Malek Horani, Khalid M. Elrabii, Anas Zayed, Hikmat Abdel-Razeq. Neoadjuvant B27 protocol in Triple-Negative Breast Cancer: Evaluation response rate, pathological complete response rates,toxicity,and the prognosis of Adolescent and Young Adult (AYA) age group compared to older population [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-06.

Plasma CXCL14 as a Candidate Biomarker for the Diagnosis of Lung Cancer.

BackgroundEffective biomarkers for early diagnosis of lung cancer are needed. Previous studies have indicated positive associations between abnormal circulating cytokines and the etiology of lung cancer.MethodsBlood samples were obtained from 286 patients with pretreatment lung cancer and 80 healthy volunteers. Circulating cytokine levels were detected with a Luminex assay and enzyme-linked immunosorbent assay (ELISA). Urine samples were obtained from 284 patients and 122 healthy volunteers. CXC chemokine ligand 14 (CXCL14) expression in tumors and nontumor regions of lung tissues from 133 lung cancer cases was detected by immunohistochemical (IHC) staining and immunofluorescence (IF) staining of formalin fixed paraffin-embedded (FFPE) tissues.ResultsCompared with healthy volunteers, a 65.7-fold increase was observed in the level of CXCL14 in the plasma of lung cancer patients, and a 1.7-fold increase was observed in the level of CXCL14 in the urine of lung cancer patients, achieving a 0.9464 AUC (area under the curve) value and a 0.6476 AUC value for differentiating between lung cancer patients and healthy volunteers, respectively. Stromal CXCL14 expression was significantly associated with advanced pathologic stage (P<0.001), pathologic N stage (P<0.001), and recurrence and metastasis (P=0.014). Moreover, multivariate analysis suggested stromal CXCL14 expression as an independent predictor of DFS and OS.ConclusionsOur study demonstrates that CXCL14 might serve as a potential diagnostic and prognostic biomarker in patients with lung cancer.ImpactCXCL14 might serve as a potential diagnostic and prognostic biomarker in patients with lung cancer.

Preoperative combination score of neutrophils, monocytes, and lymphocytes as a predictor for locally advanced rectal cancer.

The aim of this study was to investigate the prognostic value of baseline peripheral blood neutrophils, monocytes, and lymphocytes on locally advanced rectal cancer (LARC) patients. Clinicopathologic data of 317 LARC patients during July 2010 and October 2016 were retrospectively gathered. X-tile software was used to acquire the optimal cutoff values of neutrophils, monocytes, and lymphocytes. Peripheral blood immune score (PBIS) system was proposed and built based on neutrophils, monocytes, and lymphocytes. The Cox model was used to analyze the associations between clinicopathological characteristics and potential outcomes. C-index was used to assess model performance. A nomogram was constructed to predict prognosis, and a calibration plot was used to verify the accuracy of the nomogram prediction model. Cutoff values of neutrophils, lymphocytes, and monocytes were 4.46 (× 109/L), 1.66 (× 109/L), and 0.39 (× 109/L), respectively. PBIS was related to sex (P < 0.001), tumor length (P = 0.003), and tumor thickness (P = 0.014). Multivariate Cox regression analysis revealed that PBIS (HR = 0.707, 95% CI: 0.549-0.912, P = 0.008) was an independent predictor of DFS. High PBIS (HR = 0.697, 95% CI: 0.492-0.988, P = 0.043) and high lymphocyte count (HR = 0.511, 95%CI: 0.273-0.958, P = 0.036) were favorable factors of OS. Both C-index (0.74, 95% CI: 0.549-0.912) and the calibration plot showed good prediction ability of the nomogram for DFS. PBIS, composed of baseline peripheral blood neutrophils, monocytes, and lymphocytes, is an independent predictor of the prognosis of LARC. Combination of PBIS and ypTNM stage may be a promising marker to guide adjuvant therapy after the operation.

It is the lymph node ratio that determines survival and recurrence patterns in resected distal cholangiocarcinoma. A multicenter international study

BackgroundDistal cholangiocarcinoma (dCC) is still associated with a poor overall survival (OS). This study aims to investigate the impact of novel prognostic scores in comparison with more traditional ones. MethodsMulticentric retrospective analysis of patients who underwent a pancreatoduodenectomy (PD) for dCC. An unadjusted analysis was used to identify predictors of decreased survival. Significant variables were introduced in a multivariable model that assessed OS, recurrence-free survival (RFS), early recurrence (defined as a recurrence within the first 12 months from the PD), local and distant recurrence. Prognostic scores evaluated included the TNM staging system, the lymph-node ratio (LNR), the platelet-lymphocyte ratio (PLR), the neutrophil-lymphocyte ratio (NLR) and the systemic inflammation index (SII). ResultsThe study included 232 patients with resected dCC. The optimal cut-off value for LNR was 15% (LNR15). On the unadjusted analysis T stage (p = 0.012), N stage (p < 0.001), LNR15 (p < 0.001), grade (p < 0.001), perineural invasion (p < 0.001) and the R1 status of resection margin (p = 0.001) accounted for the decreased OS. No significant association between survival and PLR, NLR and SII were found.On the multivariable analysis only LNR15, perineural invasion and R1 were independent predictors of decreased RFS (p = 0.003, p = 0.021 and p = 0.009, respectively) and OS (p = 0.001, p = 0.016 and p = 0.013, respectively). Additionally, LNR15 was an independent predictor of early recurrence (p = 0.003) and both LNR15 and R1 were associated with increased local (p < 0.001 and p = 0.010) and distant recurrence (p < 0.001 and p = 0.003). ConclusionsLNR15 is an independent predictor of DFS, OS, early, local and distal recurrence, combined with the status of the resection margin and perineural invasion.

Identification of proteins associated with treatment response of neoadjuvant chemoradiotherapy in rectal mucinous adenocarcinoma by co-expression network analysis based on proteomic analysis

For rectal mucinous adenocarcinoma (MAC), identifying biomarkers of neoadjuvant chemoradiotherapy (NCRT) response has become imperative. This study applied label-free mass spectrometry and weighted gene co-expression network analysis to identify hub proteins in association with the NCRT response in 20 rectal MAC patients. We identified 131 differentially abundant proteins and 7 candidate proteins associated with the NCRT response. The immunostaining expressions of six proteins (ENOA, ILEU, MDHM, RM11, PTGDS, and RL3) were significantly associated with the NCRT response. Logistic regression analysis revealed that ENOA (OR = 6.275, P = 0.006) was independent risk hub protein for the NCRT response. Tow hub proteins (ENOA and PTGDS) were identified as significant risk factors by Cox regression analysis. A prognostic risk score system was constructed: risk score = (0.910 × EXPENOA) + (−1.519 × EXPPTGDS), and found to be an independent predictor of DFS in rectal MAC patients (HR = 10.308, P < 0.001). Our study suggested that ENOA may be a novel biomarker for the NCRT response and prognosis in rectal MAC patients. A two-hub-protein-based risk score system might be used for predicting tumor recurrence in rectal MAC patients. SignificanceNCRT resistance is a major problem in the treatment of rectal MAC patients. Identifying robust predictive biomarkers for NCRT resistance is beneficial to the stratified treatment of rectal MAC patients. In this study, label-free mass spectrometry and weighted gene co-expression network analysis identified ENOA as a potential novel biomarker for the NCRT response and prognosis. ENOA may be involved in the process of the NCRT resistance and tumor recurrence through the carbon metabolism pathway.

Clinicopathological correlation of stem cell markers expression in oral squamous cell carcinoma; relation to patients` outcome

ABSTRACT Background: Squamous cell carcinoma (OSCC) is the commonest oral malignancy.The overall 5 year survival of OSCC has remained at 50%, largely unchanged for 40 years. CSCs are important within the development, invasion, drug resistance, and prediction of carcinomas treatment outcome. ALDH1 and CD44 are commonly used epithelial tumors cancer stem-like cells surface markers. Materials: Our study aimed to judge CD44 and ALDH1 immunohistochemical expressions in 44 cases of OSCC and relates the expression to patients’ survival. Results: High CD44 & ALDH1 expressions were significantly expressed in variable histologic grades of OSCCs, large sized carcinomas, presence lymph vascular invasion, presence of nodal and distant metastasis, advanced TNM clinical stage, recurrence and death during follow up period (P ≤ 0.05). Reduced DFS and three years overall survival were significantly recorded in cases with high CD44 expression, and high ALDH1 expression (p < 0.05). CD44 & ALDH1 expressions, histologic grade, tumor size were the independent predictors of DFS and three years OS. Conclusion: CD44 and ALDH1 expressions are valuable prognostic factors in OSCC and could be well considered predictors for patients’ 3 years OS and DFS.

Construction of the Prediction Model for Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy Based on Pretreatment Tumor-Infiltrating Macrophage-Associated Biomarkers.

PurposeTo assess the value of macrophage-related biomarkers (CD163, CD68, MCSF, and CCL2) for predicting the response to neo-chemoradiotherapy (NCRT) and the prognosis of locally advanced rectal cancer (LARC).MethodsWe enrolled 191 patients who underwent neoadjuvant chemoradiotherapy and radical resection between 2011 and 2015. Tumor tissues were collected before NCRT with a colonoscope and post-surgery and were subjected to immunohistochemical analysis.ResultsThe expression levels of macrophage-related biomarkers (CD163, CD68, MCSF, and CCL2) were lower in the pathological complete response (pCR) group when compared with the non-pCR group (all P<0.05). Based on X-tile plots, we divided the tumors in two groups and found that lower pre-NCRT/post-surgical CD163, CD68, MCSF, CCL2 scores correlated with improved DFS. Cox regression analysis demonstrated that pre-NCRT CD163 (HR=1.008, 95% CI 1.003–1.013, P=0.003) and MCSF (HR=2.187, 95% CI 1.343–3.564, P=0.002) scores were independent predictors of DFS. Based on Cox multivariate analysis, we constructed a risk score model with a powerful ability to predict pCR in LARC patients. Moreover, COX regression analysis was performed to explore the role of the risk score in LARC patients. The results demonstrated that tumor size (HR=1.291, P=0.041), worse pathological TNM stage (HR=1.789, P=0.005, and higher risk score (HR=1.084, P<0.001) were significantly associated with impaired disease-free survival. Based on the above results, a nomogram and decision curve analysis were generated.ConclusionThe expression levels of macrophage-related biomarkers CD163, CD68, MCSF, and CCL2 were associated with chemoradiotherapy resistance and prognosis in LARC patients following NCRT. A risk score model was constructed which could be used to predict LARC outcome.

High Pretreatment LDH Predicts Poor Prognosis in Hypopharyngeal Cancer.

BackgroundElevated pretreatment lactate dehydrogenase (LDH) has been associated with poor prognosis in various malignancies; however, its prognostic role in hypopharyngeal cancer remains elusive. In this study, we aimed to assess the association between pretreatment LDH and clinical outcome of hypopharyngeal cancer.MethodsWe retrospectively collected 198 hypopharyngeal cancer patients treated with surgery in our institution between 2004 and 2018. The prognostic role of pretreatment LDH was explored by using univariate and multivariate analyses. Besides, subgroup analysis was performed based on T stage.ResultsThree-year and Five-year of disease-free survival (DFS, 67.0 vs. 57.4%, 65.8 vs. 39.8%, p = 0.007) and overall survival (OS, 74.8 vs. 68.9%, 66.8 vs. 50.8%, p = 0.006) exhibited significant differences between low LDH level and high LDH level groups. Univariate analysis showed that pretreatment elevated serum LDH served as an unfavorable determinant with regard to DFS and OS. Further multivariate analysis also confirmed that LDH was an independent predictor for DFS and OS. Additionally, N status and age were also found to be significantly associated with both DFS and OS.ConclusionPretreatment elevated serum LDH is an inferior prognostic factor for patients with hypopharyngeal cancer. These results should be validated by more multicenter and prospective studies.

It is Not the N Status but the Lymph Node Ratio to Determine Survival and Recurrence Patterns in Resected Distal Cholangiocarcinoma

Background: Distal cholangiocarcinoma (dCC) is still associated with poor overall 5-year survival. This study aims to investigate the impact of novel prognostic scores in comparison with the more traditional TNM staging system. Methods: Multicentric retrospective analysis of patients who underwent pancreatoduodenectomy (PD) for dCC. A biraviable analysis was used to identify predictors of decreased survival. Significant variables were introduced in a multivariable model that assessed, overall survival (OS), recurrence free survival (RFS), early recurrence (defined as a recurrence within the first 12 months from the PD), local and distant recurrence. Prognostic scores evaluated included the lymph-node ratio (LNR), the platelet-lymphocyte ratio (PLR), the neutrophil-lymphocyte ratio (NLR) and the systemic inflammation index (SII). Results: The study included 132 subjects with resected dCC. On the bivariable analysis T stage (p=0.001), N stage (p=0.001) LNR (p<0.001), grade (p<0.001), microvascular invasion (p=0.003) and the R1 status of resection margin (p=0.007) accounted for decreased OS. No significant association between survival and PLR, NLR and SII were found. The optimal cut-off value for LNR was 15% (LNR15) (AUC 0.720). On the mutivariable analysis T stage, LNR15 and R1 resulted independent predictors of decreased RFS (p=0.022, p=0.006 and p=0.004) and OS (p=0.013, p=0.004 and p=0.002). Additionally, LNR15 and R1 resulted independent predictors of early recurrence (p=0.019 and p<0.001), local recurrence (p=0.001 and p=0.013) and distant recurrence (p=0.012 and p=0.007). Conclusions: LNR 15, but not the N status is an independent predictor of DFS, OS, early, local and distal recurrence, together with the status of resection margin.

Circulating Tumor-Cell-Associated White Blood Cell Clusters in Peripheral Blood Indicate Poor Prognosis in Patients With Hepatocellular Carcinoma

Aim: Circulating tumor cells (CTC) are a precursor to metastasis in several types of cancer and are occasionally found in the bloodstream in association with immune cells, such as white blood cells (WBCs). CTC-associated WBC (CTC-WBC) clusters can promote CTC appreciation and metastasis, suggesting that patients with CTC-WBC clusters found in the peripheral blood may have a worse prognosis. However, it is unclear whether CTC-WBC clusters are present in the peripheral blood of patients with hepatocellular carcinoma (HCC) and suggest a poor prognosis for HCC.Methods: We collected peripheral blood from 214 patients with HCC from January 2014 to December 2016. CanPatrol™ CTC analysis technology was used to isolate and count CTCs and CTC-WBC clusters in the patients' peripheral blood. Chi-squared analysis was used to calculate the correlation between the CTC-WBC clusters and clinicopathological characteristics. Kaplan–Meier survival analysis and Cox regression analysis were used to assess patient prognosis.Results: We used CanPatrol™ CTC analysis technology to count different types of CTCs and CTC-WBC clusters. The results showed that CTC-WBC clusters and tumor size (P = 0.001), tumor number (P = 0.005), portal vein tumor thrombus (P = 0.026), BCLC stage (P < 0.001), AFP level (P = 0.002), and total number of CTCs (P < 0.001) were statistically related. Cox regression analysis revealed that CTC-WBC clusters are an independent prognostic indicator of DFS (HR = 1.951, 95%CI:1.348–2.824, P < 0.001) and OS (HR = 3.026, 95%CI:1.906–4.802, P < 0.001) in HCC patients. Using Kaplan–Meier analysis, we found that positive CTC-WBC cluster patients had significantly shorter DFS and OS than patients with negative CTC-WBC (P < 0.001 and P < 0.001, respectively).Conclusions: CTC-WBC clusters in the peripheral blood are an independent predictor of DFS and OS, and their presence indicates poor prognosis in patients with HCC.

Implications of Perineural Invasion on Disease Recurrence and Survival After Pancreatectomy for Pancreatic Head Ductal Adenocarcinoma.

To describe PNI and to evaluate its impact on disease-free (DFS) and overall survival (OS) in patients with resected pancreatic ductal adenocarcinoma (PDAC). Although PNI is a prognostic factor for survival in many GI cancers, there is limited knowledge regarding its impact on tumor recurrence, especially in ''early stage disease'' (PDAC ≤20 mm, R0/ N0 PDAC). This multicenter retrospective study included patients undergoing PDAC resection between 2009 and 2014. The association of PNI with DFS and OS was analyzed using Cox proportional-hazards models. PNI was found in 87% of 778 patients included in the study, with lower rates in PDAC ≤20 mm (78.7%) and in R0/N0 tumors (70.6%). PNI rate did not differ between patients who underwent neoadjuvant therapy and upfront surgery (88% vs 84%, P = 0.08). Although not significant at multivariate analysis ( P = 0.07), patients with PNI had worse DFS at univariate analysis (median DFS: 20 vs 15 months, P < 0.01). PNI was the only independent predictor of DFS in R0/N0 tumors (hazard ratio [HR]: 2.2) and in PDAC ≤ 20 mm (HR: 1.8). PNI was an independent predictor of OS in the entire cohort (27 vs 50 months, P = 0.01), together with G3 tumors, pN1 status, carbohydrate antigen (CA) 19.9 >37 and pain. PNI represents a major determinant of tumor recurrence and patients' survival in pancreatic cancer. The role of PNI is particularly relevant in early stages, supporting the hypothesis that invasion of nerves by cancer cells has a driving role in pancreatic cancer progression.

Prognostic Impact of Smoking Period in Patients with Surgically Resected Non-small Cell Lung Cancer.

The pack-year index, which is calculated by multiplying a smoking period by the number of cigarette packs smoked per day, is frequently used to investigate the risk of developing lung cancer. Notably, however, whether the smoking period or the number of packs per day is more predictive of postoperative prognosis remains unclear in non-small cell lung cancer (NSCLC) patients who receive curative lung resection. Initial screening included 2055 consecutive lung cancer patients who had underwent curative lung resection between 2000 and 2016 at a single center in Japan. Data from 1134 NSCLC patients with smoking history were ultimately analyzed. Time-dependent areas under the curve (AUCs) were used to compare diagnostic accuracy. On univariate analysis, the number of packs smoked per day was not a significant predictor of disease-free survival (DFS; p = 0.2387) or overall survival (OS; p = 0.1357). On multivariable analysis, smoking period was an independent predictor of DFS and OS (both p < 0.0001). Time-dependent smoking period AUCs were superior to those of number of packs smoked per day. On subgroup analyses, patients with a smoking period ≥ 40years had significantly shorter DFS and OS than those with a smoking period of < 40years, independent of sex, clinical stage, and histological type. Smoking period was a significant prognostic indicator in NSCLC patients who underwent curative lung resection, which should be validated in further prospective and/or multicenter studies with large sample sizes.

Impact of malnutrition and anemia at diagnosis in both: Pathological response and tumor-infiltrating-lymphocytes post neoadjuvant chemotherapy.

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.

Results of video-assisted thoracic surgery versus thoracotomy in surgical resection of pN2 non-small cell lung cancer in a Chinese high-volume Center.

To investigate the short-term outcomes and long-term oncological efficacy of video-assisted thoracic surgery (VATS) for surgical treatment of pN2 non-small cell lung cancer (NSCLC) compared with open thoracotomy (OT). We retrospectively collected data from 1034 patients who underwent pulmonary resection and systemic lymph node dissection for pathological N2 NSCLC from September 2005 to December 2017 (536 patients in VATS group and 498 patients in OT group). Propensity score matching was applied to reduce the confounding effects. Factors affecting survival were assessed by Kaplan-Meier estimates and Cox regression analysis. The VATS procedure was associated with shorter operative time compared with the OT procedure (147.96 ± 58.91min vs. 165.34 ± 58.91min, P < 0.001). No significant difference was identified between the two groups in the number of dissected mediastinal lymph nodes (MLNs) and number of dissected MLNs stations. More patients after VATS procedure received postoperative adjuvant therapy (83.4% vs. 75.5%, P = 0.002). At a median follow-up of 36 (range 4-150) months, comparing VATS procedure and OT procedure, no significant differences were noted in 5-year DFS (20.7% vs. 22.5%, P = 0.89) and 5-year OS (30.7% vs. 34.5%, P = 0.821). The VATS procedure was not found to be an independent predictor of DFS (hazard ratio, 0.986; 95% CI, 0.809 to 1.202) or OS (hazard ratio, 0.977; 95% CI 0.802 to 1.191). In this large propensity-matched comparison, the VATS procedure offered comparable short-term outcomes and long-term oncological efficacy for patients with pN2 NSCLC when compared with OT procedure.

Clinical outcomes for nasopharyngeal cancer with intracranial extension after taxane-based induction chemotherapy and concurrent chemo-radiotherapy in the modern era.

ObjectiveTo evaluate the survival outcomes for a cohort of nasopharyngeal cancer with intracranial extension (ICE) treated with induction chemotherapy (ICT) followed by chemo-intensity-modulated radiotherapy (CTRT) at a tertiary cancer center.MethodsWe retrospectively analyzed 45 patients with histologically proven, non-metastatic NPC with ICE treated at our institute between October 2008 and October 2016. Patients were classified as minor ICE or major ICE, based on the extent of ICE. All the patients received 2–3 cycles of a taxane-based ICT regimen followed by CTRT. Radiotherapy was delivered with “risk-adapted” intensity-modulated radiotherapy (IMRT) technique in all patients.ResultsAfter a median follow up of 45 months (range: 8–113 months), the estimated 5-year DFS, LRFS, DMFS, and OS of the entire cohort was 58%, 82%, 67% and 74% respectively. On multivariate analysis, histological subtype was an independent predictor of LRFS, and age was an independent predictor of DFS. The extent of ICE showed only a trend towards worse DFS (P = 0.06). None of the factors significantly predicted for DMFS or OS. Gender, N-stage, and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 22% of patients and grade 2 or worse xerostomia was seen in 24% of patients at last follow up. Thirty-three percent of the patients developed clinical hypothyroidism at last follow up. None of the patients experienced any neurological or vascular complications.ConclusionsTaxane-based induction chemotherapy followed by chemo-intensity modulated radiotherapy resulted in excellent locoregional control and survival with acceptable toxicities in patients of nasopharyngeal cancer with intracranial extension. Distant metastasis continues to be the predominant problem in these patients.

Survival after surgical treatment for resectable perihilar cholangiocarcinoma

Background. Surgical resection of perihilar cholangiocarcinoma (pCCA) offers the only chance for long-term survival, but it is associated with high morbidity and mortality rates. The aim of this monocentric retrospective cohort study was to analyze clinical and oncological outcomes after curative resection of pCCA and to determine prognostic factors. Methods. Ninety consecutive patients (F/M ratio 36/54; median (range) age 64 (30-80) years) with pCCA underwent surgical resection with curative intent between 1998-2017. An R0-resection was obtained in 76 (84%) patients. Systemic chemotherapy was given in 4 patients before and in 14 patients after surgery. The impact of 23 prognostic factors on survival was evaluated using univariable and multivariable Cox regression models. Patients were followed up until death or until the date of study closure on December 2018, with a median follow-up time of 23,6 (0–236) months. Results. Postoperative complications occurred in 74 (82%) patients. Severe complications (TOSGS grade >3a) were observed in 42 (47%) patients, including 8 (9%) deaths. Median OS time was 31 (23–44) months and DFS 29 (20-52) months. OS and DFS rates at 5 and 10 years after surgery were 32.7% and 19.2%, and 36.3% and 29.8%, respectively. Independent predictors of OS were intraoperative blood transfusion (HR 2.218, CI 1.151-4.342, p=0.017), depth of tumor wall penetration (pT; HR 2.573, CI 1.168-5.215, p=0.021) ), locoregional lymph node metastasis (pN; HR 1.877, CI 1.043-3.427, p=0.035), and tumor differentiation grade (pG; 2 vs1: HR 3.601, CI 1.428-10.085, p=0.006; pG 3 vs1: HR 3.124, CI 1.163-9.096, p=0.023). Independent predictors of DFS were portal vein resection (HR 2.723, CI 1.258-5.871, p=0.011) and locoregional lymph node metastasis (pN; HR 2.198, CI 1.017-4.700, p=0.045). Conclusion. Curative surgery for perihilar cholangiocarcinoma is a high-risk procedure with poor long-term survival. Tumor characteristics (pT, pN, pG) and intra-operative blood transfusion determine overall survival.

300P - Outcome of triple negative inflammatory breast cancers (TNIBC) treated with dose dense neoadjuvant epirubicin cyclophosphmide, prognostic impact of pre and post neoadjuvant chemotherapy (NAC) tumour infiltrating lymphocytes (TIL) and post NAC lymphovascular invasion

BackgroundInflammatory breast cancers (IBC) particularly triple negative (TN) subtype have poor prognosis. MethodsBetween January 2010 and December 2016, all patients with TNIBC seen at breast cancer disease center, St Louis hospital, Paris, France, were treated with neoadjuvant dose dense Cyclophophamide (1.2g/m2 d1) - Epirubicin (75mg/m2 d1) q2w (SIM regimen) followed with 12 injections of paclitaxel (80mg/m2) qw or 4 injections of docetaxel (100mg/m2) q3w. All patients have histologically proven TN tumors and no evidence of metastases. Mastectomy and axillary clearance was performed after chemotherapy. pCR was defined as no residual invasive tumor in breast and lymph nodes. TIL and lymphovascular invasion were evaluated pre and post NAC by 2 independent anatomopathologists dedicated to breast cancer. Delta TIL was defined as the difference between post chemotherapy and pre chemotherapy TIL. ResultsThirty TNIBC patients were treated, 28 underwent surgery and 2 progressed during chemotherapy. Median follow-up was 45 months (8 – 103). 9/30 patients (30%) achieved pCR. Median disease free survival was not reached. Median TIL infiltration at diagnosis was 11% (0-60) and dropped to 1% after chemotherapy (0 – 80). On univariate analysis, LVI after chemotherapy (HR=2.1 [95% CI, 1.1–3.6], p=0.02), TIL on mastectomy (HR=1.8 [95% CI, 1.1–3.1], p=0.03), delta TIL (HR=2.2 [95% CI, 1.4–3.5], p=0,001) were associated with DFS but no pCR (p=0,051). On multivariate analysis, only delta TIL remainedstatistically significant (HR=1.9 [95% CI, 1.1–3.4], p=0.03). ConclusionsWe showed in this retrospective series of 30 TNIBC that dose dense dose intense chemotherapy is efficient in this population. Delta TIL is a strong prognostic factor associated with DFS. We show that a positive Delta TILis, among others, a strong and independent predictor of DFS: in TNIBC contrary to the results obtained in TN non inflammatory breast cancers, an increase in TIL after chemotherapy is associated with a decrease in DFS.The exact impact of LVI must be further investigated. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.