Prognostic Factor For Relapse-free Survival Research Articles

Presurgical anemia as a predictor of relapse and survival in bladder carcinoma treated with cystectomy.

382 Background: Bladder carcinoma is the fifth most common neoplasm in developed countries. When muscle-invasive disease is diagnosed in a localized stage, radical cystectomy is the standard treatment, with or without perioperative chemotherapy. In this retrospective study we aim to identify presurgical factors that correlate with relapse risk and survival in patients being treated with radical cystectomy without neoadjuvant chemotherapy. Methods: Patients with a history of radical cystectomy for non-metastatic muscle-invasive bladder carcinoma from 1995 to 2010 were included. They had to have an appropriate follow-up, and tissue available for further correlative studies. Demographic baseline features and therapy outcomes were collected in a retrospective fashion. Results: A total of 158 patients were included, with a median overall survival (OS) for the entire cohort of 51 months (95% IC: 17.1–84.9 months). Median relapse free survival (RFS) is 39 months (95% IC: 3.8–74.1 months). In univariate analysis, the following features were prognostic factors for RFS: ECOG performance status (0 vs ³1; 72 vs 20 months, p=0.014), hemoglobin levels (normal vs low; 144 vs 21 months, p=0.001), free surgical margins (yes vs no; 39 vs 11 months, p=0.004), lymph node status (pN0 vs pN+; 119 vs 18 months, p<0.001) and pT stage (pT2 vs pT3-4; 167 vs 20 months, p< 0.001). Other previously described factors, such as neutrophil-lymphocite ratio, thrombocytosis, creatinine clearance or the presence of hydronephrosis, were not significant in our group of patients. In the multivariate analysis, only ECOG (HR 2.32), lymph node status (HR 2.0) and hemoglobin levels (HR 1.71) were independent predictors for RFS. Conclusions: In our group of patients, apart from ECOG performance status and lymph node status, the presence of presurgical anemia could be an indicator of poorer outcomes after cystectomy. These patients should be monitored closely and maybe considered for further therapeutic procedures, such as adjuvant systemic therapy.

Clinical significance of cancer specific methylation of the CDO1 gene in small bowel cancer.

Although small bowel cancer (SBC) is extremely rare, its prognosis is poor, and molecular mechanism of the SBC development remains unclear. The aim of our study is to elucidate whether DNA methylation of the promoter region of the cancer-specific methylation gene, cysteine dioxygenase 1 (CDO1), contributes to the carcinogenic process in SBC. The study group comprised patients with 53 patients with SBC, 107 colorectal cancer (CRC), and other rare tumors of the small intestine such as 4 malignant lymphomas, 2 leiomyosarcomas, and 9 gastrointestinal stromal tumors. We analyzed the extent of methylation in each tissue using quantitative TaqMan methylation-specific PCR for CDO1. Significantly higher CDO1 methylation was observed in cancer tissues compared with non-cancerous mucosa of the small intestine (ROC = 0.96). Among the various clinicopathological factors, positive correlation of CDO1 methylation with tumor diameter was observed (R = 0.31, p = 0.03), and the CDO1 methylation level was a possible prognostic factor for relapse-free survival (p = 0.09). Compared with CRC, SBC had a significantly poorer prognosis (p = 0.007) and displayed a significantly higher CDO1 methylation level (p < 0.0001). Intriguingly, especially in pStage I/II, there were robust prognostic difference between SBC and CRC (p = 0.08 / p < 0.0001), which may reflect CDO1 methylation status (p = 0.02 / p = 0.001). Among small bowel tumors, CDO1 methylation in SBC was higher in order of malignant lymphoma, cancer, and leiomyosarcoma/GIST (p = 0.002) by ANOVA. The CDO1 gene shows extremely cancer-specific hypermethylation, and it can be a prognostic marker in SBC.

Immune cell infiltration as a biomarker for the diagnosis and prognosis of stage I\u2013III colon cancer

Tumour-infiltrating immune cells are a source of important prognostic information for patients with resectable colon cancer. We developed a novel immune model based on systematic assessments of the immune landscape inferred from bulk tumor transcriptomes of stage I–III colon cancer patients. The “Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT)” algorithm was used to estimate the fraction of 22 immune cell types from six microarray public datasets. The random forest method and least absolute shrinkage and selection operator model were then used to establish immunoscores for diagnosis and prognosis. By comparing immune cell compositions in samples of 870 colon cancer patients and 70 normal controls, we constructed a diagnostic model, designated the diagnostic immune risk score (dIRS), that showed high specificity and sensitivity in both the training [area under the curve (AUC) = 0.98, p < 0.001] and validation (AUC 0.96, p < 0.001) sets. We also established a prognostic immune risk score (pIRS) that was found to be an independent prognostic factor for relapse-free survival in every series (training: HR 2.23; validation: HR 1.65; entire: HR 2.01; p < 0.001 for all), which showed better prognostic value than TNM stage. In addition, integration of the pIRS with clinical characteristics in a composite nomogram showed improved accuracy of relapse risk prediction, providing a higher net benefit than TNM stage, with well-fitted calibration curves. The proposed dIRS and pIRS models represent promising novel signatures for the diagnosis and prognosis prediction of colon cancer.

Impact of the epidermal growth factor receptor mutation status on the prognosis of recurrent adenocarcinoma of the lung after curative surgery

BackgroundThe prognosis of patients with epidermal growth factor receptor (EGFR) mutant adenocarcinoma of the lung (Mt) and EGFR wild-type adenocarcinoma (Wt) after complete resection of the lung differ; however, the mechanisms responsible for these differences remain unclear. The present study examined the post-operative prognosis of recurrent pulmonary adenocarcinoma patients to evaluate the clinicopathological nature of Mt and contribution of EGFR - tyrosine kinase inhibitors (TKI) to the prognosis of patients.MethodsThe subjects were 237 patients with recurrent pulmonary adenocarcinoma who underwent EGFR mutation analysis, and consisted of 108 patients with recurrent Mt and 129 with recurrent Wt. Multivariate analyses were performed to investigate whether the EGFR status is a prognostic factor for relapse-free survival (RFS) and post-relapse survival (PRS).ResultsRFS was significantly better in Mt than in Wt patients; median RFS were 20.2 and 13.3 months, respectively (p < 0.001). The multivariate analysis identified EGFR mutation as an independent prognostic factor for a favorable RFS (hazard ratio = 0.68; 95% confidence interval, 0.52–0.89). Although, no significant differences were observed in PRS between Mt and Wt patients (median PRS were 33.9 and 28.2 months, respectively; p = 0.360), PRS was significantly better in Mt with EGFR - TKI than in Wt and Mt patients without EGFR - TKI (p = 0.008 and p < 0.001, respectively). PRS was also significantly better in Wt than in Mt patients without EGFR - TKI (p < 0.001). The multivariate analysis identified the administration of EGFR - TKI as an independent prognostic factor for PRS (hazard ratio = 0.60; 95% confidence interval, 0.40–0.89).ConclusionsEGFR mutation tumors were associated with a significantly better RFS for recurrent pulmonary adenocarcinoma after curative resection of the lung, which represented the less aggressive nature of Mt tumors. However, patients with Mt did not have a favorable prognosis after recurrence unless they received EGFR - TKI.

Lipoprotein (a): a promising prognostic biomarker in patients with hepatocellular carcinoma after curative resection.

PurposeThis study aimed to explore serum lipoprotein (a) (Lp(a)) levels and investigate their prognostic value in hepatocellular carcinoma (HCC) patients after curative resection.Materials and methodsOne cohort of 102 healthy individuals, one cohort of 172 HCC patients, and one cohort of 171 HCC patients undergoing curative resection were studied to evaluate serum Lp(a) levels and their prognostic significance, using Kaplan–Meier curves and log-rank tests.ResultsThe Lp(a) levels in HCC patients were significantly lower than those in healthy individuals. Furthermore, the levels in HCC patients were significantly associated with recurrence. HCC patients were stratified into high Lp(a) (>20 mg/L) and low Lp(a) (≤20 mg/L) groups, using an optimal cutoff point for the Lp(a) of 20 mg/L. Low Lp(a) levels significantly correlated with tumor recurrence and survival time; HCC patients with low Lp(a) levels had higher recurrence rates and shorter survival time than those with high Lp(a) levels; Lp(a) was an independent prognostic factor for relapse-free survival and overall survival, and retained its prognostic value for α-fetoprotein ≤400 ng/mL and tumor size ≤5 cm subgroups in the training and validation cohorts.ConclusionLp(a) was a promising and useful marker for assessing and monitoring recurrence and prognosis of patients with HCC, and improving Lp(a) levels may be a promising therapeutic strategy in HCC patients.

Role of P-53 Gene in Preventing Breast Cancer

Breast cancer affects more than one million patients annually in the world and is a leading cause of mortality. Histological type, grade, tumor size, lymph node involvement, and estrogen receptor and HER-2 receptor status, all influence prognosis and the probability of response to systemic therapies. P53 gene is mutated in about 30% of breast cancers/.The possible links between alterations of p53 and clinical or pathological features of breast tumors have been widely investigated. The first study to examine gene-expression patterns of breast cancer suggested that at least four major molecular classes of breast cancer exist: luminal-like, basal-like, normal like, and HER-2 positive. Basal-like breast cancer account for 15% of breast cancers and are often described as triple negative breast cancers (TNBCs). In fact, TNBCs, defined by lack of expression of estrogen receptor, progesterone receptor, and HER2, probably include both basal-like breast cancers and some poorly differentiated luminal breast cancers. They are also associated with a younger age and a poor prognosis. TNBCs also have an increased frequency of TP53 mutations. Recently, it was shown that mutant p53 status was a strongly unfavorable prognostic factor for relapse-free survival and overall survival only in a triple negative group in patients treated with adjuvant anthracycline-containing chemotherapy. Inflammatory breast cancer (IBC) is a clinical diagnosis known as the T4d category in the TNM classification. It is a distinct clinical subtype of locally advanced breast cancer (LABC), with a particularly aggressive behavior and poor prognosis. TP53 mutations are more frequent in inflammatory breast cancer (50%) than in non-inflammatory breast cancer (20–30%). The results from these studies served as the justification for attempts to vaccinate patients using p53-derived peptides, and a number of clinical trials are in progress. The most advanced work used a long synthetic peptide mixture derived from p53 (p53-SLP; Netherlands).The vaccine is delivered in the adjuvant setting and induces T helper type I response in the majority of patients. However, the response may not be potent enough to result in clinical benefit as a mono-therapy because most patients had T-helper cells that failed to produce key cytokines, indicating that this treatment should also be associated with another type of conventional or immunotherapy therapy.

5-years RFS and prognostic factors study in HR-positive HER2-negative breast cancer patients treated with neoadjuvant endocrine therapy : Pooled analysis of two phase II trials

Background Few data are available on survival of breast cancer (BC) patients (pts) treated with neoadjuvant endocrine therapy (NET). Understanding how tumor response to NET is related to relapse risk would help clinicians make decisions about additional treatments for these pts. Methods The primary objective was to assess 5-years relapse-free survival (RFS) in previously published two sister phase II studies evaluating anastrozole and fulvestrant as NET in post-menopausal HR-positive/HER2-negative BC pts (CARMINA02 NCT00629616 ; HORGEN NCT00871858 ). Prognostic factors of RFS were explored by pooling the two databases : age ( 70), tumor and node staging, histological type and grade, clinical response, pathological response according to the Sataloff classification, baseline and surgical ER Allred score and Ki-67 expression, treatment arm, preoperative endocrine prognostic index (PEPI) score, adjuvant chemotherapy. The factor study (Horgen vs. Carmina02) was also introduced in the model as covariate. Univariate and multivariate Cox regression analysis (covariates from univariate model with P-value Results Intention-to-treat analysis is available for 217 of 236 pts included in the two trials. Post-menopausal pts with T2–T4, N0–N1, M0, HR-positive/HER2-negative BC were randomized to receive anastrozole (PO, 1 mg daily) or fulvestrant (IM, 500 mg on D1, D15 and D29 and then every 4 weeks) for 4 to 6 months before surgery. Mean age at diagnosis was 71.2 years. Baseline tumor characteristics were : 73.7 % T2, mean tumor size 44.3 mm, 66.4 % N0, 19.4 % SBR grade 1, 98.6 % ER Allred score 6-8, mean Ki67 score 17.5 % with Ki67 > 20 % in 29.5 % of cases. A clinical response (complete or partial) was observed in 50.2 % of pts and pathological response rate defined as TA or TB and NA or NB was 15.7 %. Mean Ki67 at surgery was 8.8 % (11.4 % of cases > 20 %). Among the pts, 12.4 % were classified in PEPI risk group I (risk score 0), 35.5 % in group II (score 1–3) and 30.4 % in group III (score > 4) (PEPI not available for 21.7 % of pts) ; 21.7 % of pts received adjuvant chemotherapy. Median follow-up is 65.2 months. RFS and overall survival at 5 years are 83.7 % [95 % CI : 77.9–88 %] and 92.7 [95 % CI : 88.2–95.6 %] respectively. On univariate analysis, tumor staging (T3–4 versus T2, P = 0.0001) and PEPI score (I + II versus III, P = 0.0004) are associated with RFS. So far, no relapses/death have been observed in pts with pathological response (n = 34, 15.7 %). Multivariate analysis (T, baseline Ki67, ER Allred score at surgery, PEPI and study) shows that PEPI group III is associated with significantly worse RFS (P = 0.0014, HR : 3.9 [95 % CI : 1.7–9.0]). Conclusion Post-menopausal HR-positive/HER2-negative BC pts receiving NET have a very favorable outcome. Within this population eligible for NET, the PEPI score identifies a subset of pts of poorer prognosis who are candidate for further additional treatment like chemo/or targeted therapies. The PEPI may be a tool routinely used for individualization of adjuvant treatment in NET setting. According to recent published studies, further analysis will be performed with Ki67 > 10 % and PEPI risk (group I versus groups II–III).

P-53 Gene As Marker in Breast Cancer

Purpose: Aim of this current review is to emphasis a possible links between alterations of P-53 gene together with its protein in pathological features of breast cancer. Design: The study examines the gene-expression patterns of breast cancer suggested that at least four major molecular classes of breast cancer exist: luminal-like, basal-like, normal like, and HER-2 positive. Basal-like breast cancer account for 15% of breast cancers and are often described as triple negative breast cancers (TNBCs). In fact, TNBCs, defined by lack of expression of estrogen receptor, progesterone receptor, and HER2, probably include both basal-like breast cancers and some poorly differentiated luminal breast cancers. They are also associated with a younger age and a poor prognosis. TNBCs also have an increased frequency of TP53 mutations. Inflammatory breast cancer (IBC) is a clinical diagnosis known as the T4d category in the TNM classification. It is a distinct clinical subtype of locally advanced breast cancer (LABC), with a particularly aggressive behavior and poor prognosis. Results: TP53 mutations are more frequent in inflammatory breast cancer (50%) than in non-inflammatory breast cancer (20-30%). Histological type, grade, tumor size, lymph node involvement, and estrogen receptor and HER-2 receptor status, all influence prognosis and the probability of response to systemic therapies. P53 gene is mutated in about 30% of breast cancers. Conclusion: Recently studies shown that mutant P-53 gene status was a strongly unfavorable prognostic factor for relapse-free survival and overall survival only in a triple negative group in patients treated with adjuvant anthracycline-containing chemotherapy. The results from these studies served as the justification for attempts to vaccinate patients using p53-derived peptides, and a number of clinical trials are in progress.

Mina53 nuclear localization is an important indicator of prognosis in patients with colorectal cancer after adjuvant chemotherapy.

The aim of this study was to investigate the status of the c‑Myc‑related molecule Mina53 and the clinical impact of Mina53 nuclear localization in patients with stageII andIII colorectal cancer (CRC). Patients (n=250) who underwent complete resection of CRC at our department were enrolled in this study, and tissue microarray samples were constructed from resected specimens. Mina53 expression in the nuclei of tumor cells was analyzed using immunohistochemistry (IHC). Patients were classified into Mina53 nuclear localization‑-positive and ‑negative groups, and statistical correlations with clinicopathological factors were investigated. Relapse‑free survival (RFS) was compared using the Kaplan‑Meier method and the Cox proportional hazard model. Tumor recurrence was significantly higher in the Mina53‑positive group than in the Mina53‑negative group. Moreover, in RFS analysis, patients in the Mina53‑positive group exhibited significantly poorer prognosis than patients in the Mina53‑negative group. In the univariate analysis, histological type, adjuvant chemotherapy status, carcinoembryonic antigen (CEA) status, and Mina53 status were prognostic factors for RFS. Furthermore, in the subgroup analysis, patients in the Mina53‑positive group with stageIII disease treated with adjuvant chemotherapy exhibited significantly poorer prognosis in RFS than patients in the Mina53‑negative group. In the univariate and multivariate analyses, histological type and Mina53 status were significantly associated with RFS. Thus, our findings revealed that Mina53 was an important indicator of prognosis in patients with stageIII CRC treated with adjuvant chemotherapy.

Impact of the 21-gene recurrence score assay in clinical treatment and prognosis analysis for patients with hormone receptor positive early-stage breast cancer

Objective: To explore the association between the 21-gene recurrence score (RS) and clinicopathologic characteristics as well as prognosis in patients with axillary lymph node negative, hormone receptor (HR) positive breast cancer. Methods: The clinicopathologic data of 439 early breast cancer patients who underwent 21 gene RS testing was retrospectively analyzed. According to the 21 gene RS, the patients were divided into low risk (295 cases), intermediate risk (111 cases) and high-risk (33 cases) group. The relationship between the 21 gene RS and clinicopathological characteristics, treatment, recurrence and metastasis was analyzed. Univariate and multivariate statistical analyses were used to analyze the risk factors for relapse free survival (RFS). Results: Tumor grade, estrogen receptor (ER), progesterone receptor (PR) and Ki-67 index were significantly different among the 3 risk cohorts (P<0.001 for all). After a median follow-up of 32 months, the recurrence rate in low risk group (3.7%) was significantly lower than that in the intermediate-high risk group (9.0%), the locoregional recurrence (LRR) rate of low, intermediate and high risk group was 2.4%, 6.3% and 9.1%; and the distant metastasis (DM) rate in low risk group was 1.4% and 2.1% in the intermediate-high risk group. Univariate analysis showed RS, ER status and endocrine therapy were prognostic factors for RFS (P<0.05 for all). Multivariate analysis showed that RS was an independent significant predictor for RFS (P=0.04). Conclusions: The 21-gene RS is related to tumor grade, ER, PR and Ki-67 index. RS is an independent risk factor for RFS in patients with hormone receptor positive early-stage breast cancer.

Therapeutic effect and prognostic factors of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Objective To explore the outcome and prognostic factors of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Methods Forty-nine newly diagnosed adult patients with Ph+ ALL were analyzed retrospectively, and the treatment effect and the impact of different factors on prognosis were explored. Results In 49 patients, there were 24 males and 25 females; the median age was 38 years (range 15-77 years). Hematologic complete remission (CR), major molecular response (MMR) and complete molecular remission (CMR) rate in patients received tyrosine kinase inhibitors (TKI) plus chemotherapy were higher than those in patients received chemotherapy only (96.8% vs. 72.2%, χ2 = 4.308, P = 0.038; 64.5% vs. 16.7%, χ 2 = 10.468, P = 0.001; 25.8% vs. 11.1%, χ 2 = 4.250, P = 0.039). With a median overall survival (OS) of 24 months (3-70 months), the 3-year OS and relapse-free survival (RFS) rates were 32.7% and 21.4%, respectively. The 3-year OS rate and 1-year RFS rate in TKI plus chemotherapy group were 40.3% and 67.8% respectively, which were higher than those in chemotherapy group (11.1% and 11.1%) (χ 2 = 12.725, χ 2 = 17.401, both P < 0.001). The 3-year OS and RFS rates in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group were higher than those in the group without allo-HSCT (62.5% vs. 25.7%, χ2 = 6.196, P = 0.013; 41.7% vs. 15.0%, χ2 = 8.032, P = 0.005). The 3-year OS and RFS rates in patients achieved MMR after 2 circles treatment were higher than those in the others (45.1% vs. 17.6%, χ2 = 5.446, P = 0.020; 28.9% vs. 11.7%, χ2 = 6.484, P = 0.011). Multivariate analysis showed that received TKI (HR = 0.227, 95% CI 0.094-0.550, P = 0.001) was an independent prognostic factor for OS; received TKI (HR = 0.225, 95% CI 0.082-0.618, P = 0.004) and allo-HSCT (HR = 0.275, 95% CI 0.077-0.983, P = 0.047) were independent prognostic factors for RFS. Conclusions TKI can increase CR, MMR and CMR rates, improve outcome, and give more chance to receive HSCT. In TKI era, allo-HSCT is still the important treatment for Ph+ ALL, especially for patients without MMR. Key words: Leukemia, acute; Philadelphia chromosome; Prognosis; Hematopoietic stem cell transplantation; Imatinib

Association of five-factor score with the mortality in Japanese patients with polyarteritis nodosa

Aim: To determine mortality and its predictive factors in Japanese patients with polyarteritis nodosa (PAN).Methods: This retrospective single-center study determined the mortality of 18 patients with PAN who were admitted to Juntendo University Hospital from 1994 to 2016. The variables at baseline, including patient demographics, clinical characteristics, and treatment, were analyzed for their association with mortality.Results: The median age of onset was 57.0 years. The 1-year survival rate was 100% (16/16) and the 5-year survival rate was 80.0% (8/10). The relationship between mortality, as defined by the survival rate and each variable was evaluated by Cox univariate analysis. A higher 2009 five-factor score (FFS) was associated with increased mortality, with a hazard ratio of 2.34 (p = .04). Analysis of the secondary outcome of relapse-free survival time revealed an association with rapid progressive renal failure, Birmingham Vasculitis Activity Score (BVAS), the 1996 FFS, and the 2009 FFS, with hazard ratios of 7.28 (p = .048), 1.26 (p = .02), 2.32 (p = .03), and 1.82 (p = .04), respectively.Conclusion: We investigated mortality, relapse-free survival, and their predictive factors in Japanese patients with PAN. The BVAS and the 1996 FFS at diagnosis may be prognostic factors for relapse-free survival, and the 2009 FFS at diagnosis may be a prognostic factor for both mortality and relapse-free survival.

Adjuvant chemotherapy for elderly patients with non-small-cell lung cancer.

Background Adjuvant chemotherapy after complete surgical resection is currently the standard of care for patients with stage IB, II, or IIIA non-small-cell lung cancer. However, the generalizability of this treatment to elderly patients is controversial. We investigated the effects of adjuvant chemotherapy in patients aged over 75 years with stage IB-IIIA non-small-cell lung cancer. Methods We retrospectively analyzed 246 consecutive patients aged over 75 years with stage IB-IIIA non-small-cell lung cancer who underwent standard lung cancer surgery between January 2001 and December 2015. They were divided into 102 who had adjuvant chemotherapy and 144 who had none (control group). The outcomes were compared between the two groups, and prognostic factors were evaluated. Results Relapse-free survival and overall survival were significantly shorter in the control group than the chemotherapy group ( p = 0.006 and p = 0.008, respectively). In multivariable analyses, adjuvant chemotherapy was found to be an independent prognostic factor for relapse-free survival and overall survival (hazard ratio = 0.594, 95% confidence interval: 0.396-0.893, p = 0.012; and hazard ratio = 0.616, 95% confidence interval: 0.397-0.957, p = 0.031, respectively). After inverse-probability-of-treatment weighting adjustment using the propensity score for baseline characteristics, chemotherapy almost improved relapse-free survival and overall survival (hazard ratio = 0.652, 95% confidence interval: 0.433-0.981, p = 0.040; and hazard ratio = 0.657, 95% confidence interval: 0.429-1.004, p = 0.052, respectively). Conclusions Adjuvant chemotherapy improved the prognosis after standard lung cancer surgery in patients aged over 75 years with stage IB-IIIA non-small-cell lung cancer.

Multivariate analysis of prognostic factors among 706 mucosal melanoma patients.

9569 Background: Mucosal melanoma is rare and associated with extremely poor prognosis. Little is known about its outcome and prognostic analysis. In this study, we evaluated prognostic factors among mucosal melanomas. Methods: The survival rates, Relapse Free Survival (RFS), Overall Survival (OS) and prognostic factors were compared for 706 mucosal melanomas at different anatomical sites. Results: Mucosal melanoma from nasal pharyngeal and oral (268 pts), upper and lower gastrointestinal (GI) (221 pts), gynecological and urological (196 pts) had a similar survival with a 1-y survival rate (88%, 83%, 86%), 2-y survival rate (66%, 57%, 61%), 5-y survival rate (27%, 16%, 20%), respectively. Multivariate analysis revealed that Depth of Invasion (p &lt; 0.001), Lymph node metastases (p &lt; 0.001), Distant metastases (p &lt; 0.001) were three independent prognostic factors for OS among 706 pts. Anatomical site (p = 0.031), Depth of Invasion (p &lt; 0.001), Lymph node metastases (p &lt; 0.001) were three independent prognostic factors for RFS among 543 pts. KPS status, Depth of Invasion, Lymph node metastases, Distant metastases were independent factors for OS among nasal pharyngeal and oral pts. Depth of Invasion, Lymph node metastases, CKIT Mutation were independent factors for RFS among nasal pharyngeal and oral pts. Gender, Lymph node metastases, Distant metastases were independent factors for OS among GI pts. Gender, Depth of Invasion, Lymph node metastases were independent factors for RFS among GI pts. Lymph node metastases, Distant metastases were independent factors for OS among Gynecological and Urological pts. Depth of Invasion, Lymph node metastases were independent factors for RFS among Gynecological and Urological pts. Conclusions: This is the first prognostic analysis for mucosal melanoma with the largest sample size for the first time. with few exceptions, It revealed that Depth of Invasion, Lymph node metastases, Distant metastases were independent prognostic factors for OS, Depth of Invasion and Lymph node metastases were independent prognostic factors for RFS. These results should be incorporated into the establishment of stage system and design of future clinical trials involving patients with mucosal melanoma.

Clinicopathological Characteristics of Hepatocellular Carcinoma with Microscopic Portal Venous Invasion and the Role of Anatomical Liver Resection in These Cases.

The aims of this study were to investigate predictive factors for microscopic portal venous invasion (mPVI) in hepatocellular carcinoma (HCC) and whether anatomical liver resection (ALR) was useful in such cases. We analyzed 852 patients with HCC without macroscopic portal venous invasion who were treated at our hospital between January 1990 and May 2014. These patients were stratified into a microscopic portal venous invasion group (mPVI group; n=153) and non-microscopic portal venous invasion group (NmPVI group; n=699). PIVKA-II ≥100mAU/ml, a tumor size ≥5cm, a confluent lesion, and poor differentiation were found to be independent risk factors for mPVI. Among the mPVI group who had single HCC under 5cm, serum albumin level <4.0g/dl, PIVKA-II ≥100mAU/ml, a positive surgical margin, and non-ALR (NALR) were independent unfavorable prognostic factors for overall survival (OS). PIVKA-II ≥100mAU/ml, a positive surgical margin and NALR were independent unfavorable prognostic factors for relapse-free survival (RFS). ALR was significantly favorable factor for both OS and RFS of the mPVI group who had single HCC under 5cm. Even if no portal venous invasion is detectable in HCC patients preoperatively, a PIVKA-II ≥100mAU/ml, tumor size ≥5cm, and a confluent lesion indicate a high risk of mPVI. ALR should be considered for the patients with these characteristics because it is a favorable prognostic factor in these cases with mPVI.

Clinical Outcomes of Perioperative Chemotherapy in Patients With Locally Advanced Penile Squamous-Cell Carcinoma: Results of a Multicenter Analysis

The prognosis of patients with locally advanced penile squamous-cell carcinoma is primarily related to the extent of lymph node metastases. Surgery alone yields suboptimal results, and there is a paucity of data on these patients' outcomes. This retrospective study evaluated patients who received neoadjuvant or adjuvant chemotherapy from 1990 onward at 12 centers. Cox models were used to investigate prognostic factors for relapse-free survival and overall survival (OS). Among the 201 included patients, 39 (19.4%) had disease of T3-4 and N0 clinical stage; the remaining patients had clinical lymph node involvement (cN+). Ninety-four patients received neoadjuvant chemotherapy (group 1), 78 received adjuvant chemotherapy (group 2), and 21 received both (group 3). Eight patients for whom the timing of perioperative chemotherapy administration was unavailable were included in the Cox analyses. Forty-three patients (21.4%) received chemoradiation. Multivariate analysis for OS (n=172) revealed bilateral disease (P= .035) as a negative prognostic factor, while pelvic cN+ tended to be nonsignificantly associated with decreased OS (P= .076). One-year relapse-free survival was 35.6%, 60.6%, and 45.1% in the 3 groups, respectively. One-year OS was 61.3%, 82.2%, and 75%, respectively. No significant differences were seen on univariable analyses for OS between the groups (P= .45). Platinum type of chemotherapy and chemoradiation were not significantly associated with any outcome analyzed. Benchmark survival estimates for patients receiving perioperative chemotherapy for locally advanced penile squamous-cell carcinoma have been provided, with no substantial differences observed between neoadjuvant and adjuvant administration. This analysis may result in improved patient information, although prospective studies are warranted.

Abstract P2-05-27: Baseline serum CA15-3 levels are associated with prognosis for breast cancer patients with non-complete pathological response to neoadjuvant chemotherapy

Abstract Background: It has been well demonstrated that patients who achieved pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) had a favorable prognosis compared with patients who did not (non-pCR). Even though pCR was not attained, reduction in tumor volume after chemotherapy may be associated with improved prognosis for a certain number of patients. However, the association between residual tumor volume and prognosis is not necessarily consistent. In order to identify substitute markers for breast cancer patients with non-pCR after NAC, we investigated the impact of serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA15-3) at baseline as well as post-NAC. Patients and Methods: Ninety-six breast cancer patients treated with NAC and operated on at the Hyogo College of Medicine were recruited for this study. Serum CEA and CA15-3 were measured prior to chemotherapy as well as at completion of pre-operative treatment. The optimal cutoff points for CEA (1.55ng/m, normal range: &amp;lt;5.0ng/ml) and CA15-3 (13.25U/ml, normal range: &amp;lt;28.0U/ml) for relapse-free survival (RFS) were determined by analyzing the area under receiver operating characteristic curves in another study involving 613 breast cancer patients. Expression levels of Ki67 in samples obtained at pre- and post-NAC were also determined by means of immunohistochemical staining. Pathological complete response was classified as the absence of residual invasive cancer in the breast and lymph nodes. During a 2.13 years median follow-up period, 15 patients suffered relapse. Results: pCR and non-pCR was attained by 21 and 75 patients, respectively. For the non-pCR patients, serum CEA levels at baseline were classified into high (n=35) and low (n=38) and serum CA15-3 levels at baseline into high (n=31) and low (n=43). RFS of non-pCR patients with high serum CA15-3 levels was significantly worse than of those with low levels (3-year RFS: 0.47 vs 0.93; p=0.0009). RFS for patients with high and low serum levels of CA15-3 after NAC was also significantly different (p=0.037). As for CEA, no significant association with RFS was observed either at baseline or post-NAC. Univariate analysis demonstrated that tumor size and baseline CA15-3 were significant prognostic factors for RFS. Multivariate analysis showed that both tumor size (hazard ratio (HR): 3.88, 95% confidence interval (CI): 1.21-12.35, p=0.023) and baseline CA15-3 (HR: 13.51, 95% CI: 1.74-105.08, p=0.013) were significant and independent risk factors for relapse. As for lymph node metastasis, tumor grade, residual tumor size and pre- and post-NAC Ki67 expression levels of patients with non-pCR showed no significant association with RFS. Conclusion and discussion: High levels of serum CA15-3 at baseline constituted a significantly worse prognosis for breast cancer patients with non-pCR. Tumor size at baseline but not residual size and baseline CA15-3 seems to suitable as a substitute for prediction of outcome for patients with non-pCR. Our findings suggest that these markers may be useful for identifying patients with poor prognosis who may be candidates for additional adjuvant treatment. Citation Format: Fujimoto Y, Imamura M, Higuchi T, Nishimukai A, Yanai A, Miyagawa Y, Murase K, Takatsuka Y, Miyoshi Y. Baseline serum CA15-3 levels are associated with prognosis for breast cancer patients with non-complete pathological response to neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-27.

Prognostic significance of the preoperative lymphocyte-to-monocyte ratio in patients with colorectal cancer.

A correlation between the lymphocyte-to-monocyte ratio (LMR) and the survival of patients with hematological malignancies has been reported previously. However, there have been few studies investigating the prognostic significance of LMR in patients with solid tumors. The aim of the present study was to evaluate the prognostic significance of preoperative LMR in patients with colorectal cancer (CRC). A total of 189 patients undergoing potentially curative surgery for CRC were enrolled. The LMR was calculated from preoperative blood samples by dividing absolute lymphocyte count by absolute monocyte count. A cut-off value of 4.8 was set based on the receiver operating characteristic curve; 116 patients were classified as high-LMR, and 73 patients classified as low-LMR. The high-LMR group exhibited significantly better relapse-free survival (P=0.0018) and overall survival (P=0.0127) rates than the low-LMR group. According to the multivariate analysis of survival, preoperative LMR was identified as an independent prognostic factor for relapse-free survival (P=0.041) and overall survival (P=0.031). Therefore, preoperative LMR is a useful prognostic marker in patients with CRC.

Evaluation of diagnostic and prognostic significance of Ki-67 index in pulmonary carcinoid tumours.

Pulmonary carcinoid (PC) tumours are classified as either typical (TC) or atypical (AC) according to mitotic index (MI) and presence of necrosis. The aim of this study was to analyse the diagnostic and prognostic values of the Ki-67 index in PC. Between January 2001 and March 2015, we evaluated 94 consecutive patients with a confirmed diagnosis of TC (n=75) or AC (n=19) at our institution. Diagnostic histology was centrally reviewed by a local expert neuroendocrine pathologist, with assessment of Ki-67, MI, and necrosis. Median patient follow-up was 35months. Eighty-four patients who underwent curative surgical resection were included in the survival analysis for identification of prognostic factors. Ki-67 index showed high diagnostic accuracy to predict histological subtype when assessed by receiver operator characteristic curves with an area under the curve of 0.923 (95% CI0.852-0.995, p<0.001). Multivariate analysis showed that MI, Ki-67 index, and the presence or absence of necrosis were independent prognostic factors for relapse-free survival. Combination of MI, Ki-67, and necrosis led to the classification of patients into four different prognostic groups (very low, low, intermediate, and high risks of relapse). The current study proposes the incorporation of Ki-67 index in the prognostic classification of PC tumours. Due to the limited number of patients and length of follow-up, the current model needs validation by larger cohort studies. Nevertheless, our results suggest that Ki-67 index and MI have continuous effect on prognosis. Prognostic models incorporating multiple cutoffs of Ki-67 and MI might better predict outcome and inform clinical decisions.

Abstract 3924: AIRE is expressed and associated with good prognosis in breast cancer

Abstract The transcription factor Autoimmune Regulator (AIRE) gene plays a fundamental role in tolerance process by promoting the ectopic expression of thousands of genes encoding for tissue-specific antigens (TSAs) in medullary thymic epithelial cells (mTECs). Beside the high expression of AIRE in mTECs, there are few evidences of AIRE expression in other lymphoid organs and very recently, AIRE was described to be expressed in human and mouse keratinocytes and in tumors originating in stratified and pseudostratified epithelia. Therefore, we evaluated the hypothesis that AIRE could be expressed by epithelial tumors and we focused on breast cancer, for which large public datasets are available. Our analysis on the TCGA, the largest public breast cancer RNA-seq dataset, revealed that AIRE is expressed in 33% of the cases, and Aire protein expression was confirmed in 26% of 115 human primary breast cancer specimens by immunohistochemistry analysis. AIRE expression was revealed associated to a better relapse-free survival in the TCGA patients and also in two public gene expression microarray-based dataset developed on Agilent and Illumina platform (NKI-295 and KM-plotter). In all the datasets analyzed, AIRE expression resulted an independent strong prognostic factor for relapse-free survival, particularly in ER-positive tumors. Ingenuity Pathway Analysis (IPA) showed that AIRE-expressing tumors were enriched in translation-related pathways, accordingly with AIRE's described function in mTECs. Moreover, in breast cancer luminal cell lines MCF-7 and MDA-MB-361 transfected with AIRE-expressing vector, a significant increase of cell in G1 phase and activation of caspases cascade were observed, supporting the hypothesis that genotoxic stress, induced by AIRE-mediated proteins over-translation, leads to cycle arrest and apoptosis. These data highlight for the first time AIRE expression in breast cancer and an association with a better prognosis was revealed. Imbalance of cellular homeostasis, caused by AIRE transcriptional function, is a new unusual mechanisms to trigger apoptosis in breast cancer cells. Citation Format: Francesca Bianchi, Loris De Cecco, Tiziana Triulzi, Sandra Romero-Cordoba, Michele Sommariva, Chiara Storti, Piera Aiello, Elda Tagliabue, Andrea Balsari, Lucia Sfondrini. AIRE is expressed and associated with good prognosis in breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3924.