Independent Prognostic Factor For Disease-free Survival Research Articles

Postoperative Adjuvant Transarterial Chemoembolization Plus Tyrosine Kinase Inhibitor for Hepatocellular Carcinoma: a Multicentre Retrospective Study.

PurposeThis study aimed to assess the efficacy and safety of adjuvant transarterial chemoembolization (TACE) plus tyrosine kinase inhibitor (TKI) treatment in patients with hepatocellular carcinoma (HCC) with a high risk of early recurrence after curative resection.Patients and MethodsPatients from multiple centres were divided into postoperative adjuvant TACE with (n=57) or without (n=142) TKI administration groups. The disease-free survival (DFS) curve was depicted by the Kaplan–Meier method, and the difference between the two groups was tested using the log rank test. Univariate and multivariate Cox analyses were performed to identify independent risk factors for DFS. Additionally, three propensity score analyses were performed to minimise the potential confounding factors to facilitate a more reliable conclusion. Adverse events (AEs) were assessed according to the Common Terminology Criteria for Adverse Events, version 4.0.ResultsThe 1-and 2-year DFS rates of the TACE plus TKI treatment group were 45.5% and 34.9%, respectively, which were significantly better than those of the TACE alone group (26.8% and 18.3%, respectively). Multivariate analysis identified adjuvant TACE plus TKI treatment as an independent prognostic factor for DFS (hazard ratio: 0.611, 95% confidence interval: 0.408–0.915, P=0.017). Further analysis based on the various propensity score methods yielded similar results. Subgroup analysis showed that patients with tumour diameter ≥5 cm, tumour number <3, absence of hepatic vein tumour thrombus and bile duct tumour thrombus, ruptured tumours, and stage IIIB could benefit more from TACE plus TKI treatment (all P<0.05). Some patients (33.33%) experienced grade ≥3 AEs in the TACE plus TKI group.ConclusionTACE plus TKI treatment can reduce the incidence of early recurrence with tolerable adverse events in HCC patients at high risk of recurrence after hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment.

Clinical significance and outcomes of bilateral and unilateral recurrent laryngeal nerve lymph node dissection in esophageal squamous cell carcinoma: A large-scale retrospective cohort study.

BackgroundThe survival benefits of recurrent laryngeal nerve lymph node dissection (RLNLD) in esophageal squamous cell carcinoma (ESCC) are still under debate, and the prognostic value of unilateral RLNLD has been rarely studied. Therefore, the aim of the present study was to investigate the clinical significance and outcomes of RLNLD in ESCC in a large‐scale cohort study, to shed light on the outcomes of unilateral RLNLD, and to identify the factors that affect the prognostic outcome of RLNLD.MethodsWe retrospectively reviewed 1153 patients with thoracic ESCC who underwent right thoracotomy with lymphadenectomy. The impact of RLNLD on disease‐free survival (DFS) and overall survival (OS) was estimated using the Kaplan–Meier method and Cox proportional hazard models. Inverse probability of treatment weighting (IPTW) was performed to adjust for differences in baseline variables in pairwise comparisons. Subgroup analysis of survival and postoperative complications was conducted for selective RLNLD.ResultsRLN lymph node (LN) metastasis was independently associated with tumor location and most other LN station metastases. RLNLD was an independent prognostic factor for DFS and OS. Both patients who underwent unilateral and bilateral RLNLD had significantly better DFS and OS than the non‐RLNLD patients. Furthermore, pairwise comparisons with IPTW confirmed these results, and we found that patients who underwent bilateral RLNLD had better survival than those who underwent unilateral RLNLD. However, subgroup analysis showed that there was no survival benefit and higher morbidity after bilateral RLNLD for patients with cancer in the lower thoracic esophagus, and elderly and female patients.ConclusionRLN LN metastasis is very frequent in ESCC, and both unilateral and bilateral RLNLD have considerable survival benefits. Selective RLNLD with better survival and lower morbidity was recommend for some defined subgroups.

The prognostic and predictive value of ESR1 fusion gene transcripts in primary breast cancer

BackgroundIn breast cancer (BC), recurrent fusion genes of estrogen receptor alpha (ESR1) and AKAP12, ARMT1 and CCDC170 have been reported. In these gene fusions the ligand binding domain of ESR1 has been replaced by the transactivation domain of the fusion partner constitutively activating the receptor. As a result, these gene fusions can drive tumor growth hormone independently as been shown in preclinical models, but the clinical value of these fusions have not been reported. Here, we studied the prognostic and predictive value of different frequently reported ESR1 fusion transcripts in primary BC.MethodsWe evaluated 732 patients with primary BC (131 ESR1-negative and 601 ESR1-positive cases), including two ER-positive BC patient cohorts: one cohort of 322 patients with advanced disease who received first-line endocrine therapy (ET) (predictive cohort), and a second cohort of 279 patients with lymph node negative disease (LNN) who received no adjuvant systemic treatment (prognostic cohort). Fusion gene transcript levels were measured by reverse transcriptase quantitative PCR. The presence of the different fusion transcripts was associated, in uni- and multivariable Cox regression analysis taking along current clinico-pathological characteristics, to progression free survival (PFS) during first-line endocrine therapy in the predictive cohort, and disease- free survival (DFS) and overall survival (OS) in the prognostic cohort.ResultsThe ESR1-CCDC170 fusion transcript was present in 27.6% of the ESR1-positive BC subjects and in 2.3% of the ESR1-negative cases. In the predictive cohort, none of the fusion transcripts were associated with response to first-line ET. In the prognostic cohort, the median DFS and OS were respectively 37 and 93 months for patients with an ESR1-CCDC170 exon 8 gene fusion transcript and respectively 91 and 212 months for patients without this fusion transcript. In a multivariable analysis, this ESR1-CCDC170 fusion transcript was an independent prognostic factor for DFS (HR) (95% confidence interval (CI): 1.8 (1.2–2.8), P = 0.005) and OS (HR (95% CI: 1.7 (1.1–2.7), P = 0.023).ConclusionsOur study shows that in primary BC only ESR1-CCDC170 exon 8 gene fusion transcript carries prognostic value. None of the ESR1 fusion transcripts, which are considered to have constitutive ER activity, was predictive for outcome in BC with advanced disease treated with endocrine treatment.

Retrospective literature review of primary neuroendocrine neoplasms of the breast (BNEN) in 209 Chinese patients: Treatment and prognostic factor analysis.

BackgroundThe prognostic factors and optimal choice of treatment for primary neuroendocrine neoplasms of the breast (BNEN) remain to be defined.MethodsPatients diagnosed with BNEN in China were retrospectively reviewed from the literature following the systematic search of China National Knowledge Infrastructure (CNKI), Chinese biomedical literature service system (sinomed), wanfang medical network, and Pubmed database. The clinical characteristics and different treatment modalities of patients with BNEN were evaluated.ResultsA total of 209 cases with BNEN were enrolled. There were 204 female and 5 male patients. The median age was 51 years old (range, 17–82). Out of 209 patients with BNEN, 208 (99.5%) patients were treated with surgery (SG), 44 patients (21.1%) had received radiotherapy (RT), 173 patients (82.8%) experienced chemotherapy (CT). A total of 158 patients with hormone receptor (HR) positive (87.8%, 158/180) were treated with endocrine treatment (ET). The median follow-up time was 52.4 months (range, 6–144). The 3-year overall survival (OS) rate and 3-year disease-free survival (DFS) rate for the whole group were 93.7% and 85.3%, respectively. In univariate analyses, Ki67 expression ≥20%, HR negative, neuroendocrine carcinomas (NECs) were associated with decreased OS and DFS (P < 0.05). Patients treated with anthracycline/taxane-containing CT regimens, or taxane-containing CT regimens had superior OS and DFS than patients without those (P < 0.05). Among 69 patients with stage I who received CT had no significant differences in OS or DFS compared to those without CT. Multivariate Cox regression analysis showed that gender, HR expression, pathologic subtype, and CT were independent prognostic factors for DFS but not OS (P > 0.05).ConclusionsThe best selection of patients to get the most benefit from different treatment modalities warrant further exploration. The clinicopathological parameters including gender, HR expression, ki67 expression, pathologic type, stage, tumor size, and lymph node status may serve as both indicators of diagnosis and prognosis, and guide treatment decisions for BNEN.

Use of the Advanced Lung Cancer Inflammation Index as a Prognostic Indicator for Patients With Cholangiocarcinoma.

BackgroundThis study aimed to assess the clinical utility of the advanced lung cancer inflammation index (ALI) as a prognostic indicator for patients with cholangiocarcinoma (CCA) and construct a prognostic nomogram based on ALI.MethodsA total of 97 CCA patients who received radical resection were included. The optimal cut-off point for ALI was identified by X-tile analysis. COX regression analysis were used to identify risk factors of overall survival (OS) and disease-free survival (DFS). A predictive nomogram for DFS was constructed.ResultsThe optimal cut-off value for preoperative ALI was 31.8. 35 (36.1%) patients were categorized into the low-ALI group and 62 (63.9%) patients into the high-ALI group. Low ALI was independently associated with hypoproteinemia and lower body mass index (BMI) (all P < 0.05). COX regression analysis revealed that preoperative ALI level (HR = 0.974, P = 0.037) and pathological TNM stage (HR = 7.331, P < 0.001) were independently correlated with OS for patients with CCA, and preoperative ALI level (HR = 0.978, P = 0.042) and pathological T stage (HR = 1.473, P = 0.035) remained to be independent prognostic factors for DFS in CCA patients. Using time-dependent ROC analysis, we found that ALI was better at predicting prognosis than other parameters, such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI) in terms of OS and DFS. A nomogram predicting DFS was built (C-index: 0.73 95%CI: 0.67–0.79).ConclusionsALI may be useful for prognosis assessment for patients with CCA.

Prognostic Significance of the Serosal Invasion in Hepatocellular Carcinoma

Background: The prognostic significance of serosal invasion (SI) was not clarified in patients with hepatocellular carcinoma (HCC). We investigated the impact of serosal invasion (SI) for the long-term outcome after curative surgical resection in patients with HCC. Methods: In total, 783 consecutive patients with HCC who underwent curative surgical resection without any preoperative treatment were histologically evaluated for SI. Patients with SI were classified into two groups: positive for SI (pSI; n=333) and negative for SI (nSI; n=450). Clinicopathologic features, disease-free survival (DFS), and overall survival (OS) were compared between patients with pSI and nSI. Results: The pSI group showed more aggressive tumor characteristics, such as higher tumor marker levels (alpha-fetoprotein, P=.023; protein induced by vitamin K absence-II, P=.016), larger tumor size (P<.001), higher prevalence of microvascular invasion (P=.002), and poorer differentiation (P=.002), than the nSI group. In survival analysis, 5-year DFS was 48.1%, 61.2% in the pSI, nSI, respectively (P<.001), while 5-year OS was 74.8%, 86.1%, respectively (P=.002). In multivariate analysis, SI was an independent prognostic factor for DFS (P=.043) and OS (P=.042). Conclusions: The SI was associated with more aggressive clinicopathologic characteristics and a higher risk of poor survival. Therefore, intensive careful follow-up is essential for patients with pSI after curative surgical resection in patients with HCC.

TRIM39 is a poor prognostic factor for patients with estrogen receptor-positive breast cancer and promotes cell cycle progression.

Tripartite motif (TRIM) family proteins are involved in various biological processes and the pathophysiology of cancers. However, the roles of TRIM39, a TRIM family member, in breast cancer is not well-understood. Here, we performed immunohistochemical study of TRIM39 protein in clinical estrogen receptor-positive (ER+ ) breast cancer tissues from 108 patients. TRIM39 immunoreactivity (IR) was positively correlated with advanced stage (p < 0.001), large invasive tumor size (p = 0.012), and positive lymph node status (p = 0.002). Positive TRIM39 IR was significantly correlated with short disease-free survival (DFS) (p = 0.001). Multivariate analysis revealed that the TRIM39 status is an independent prognostic factor in DFS (p = 0.049). Microarray analysis of MCF-7 breast cancer cells treated with siRNA revealed that TRIM39 knockdown downregulated the cell cycle- and cell division-related genes, including MLLT11, CDCA3, CDC25C, BIRC5, and ANP32E. Consistently, TRIM39 knockdown significantly suppressed proliferation and cell cycle transition to S phase in MCF-7 and 4-hydroxytamoxifen-resistant (OHTR) breast cancer cells. These results suggest that TRIM39 promotes ER+ breast cancer growth by promoting cell cycle progression.

Significance of preoperative blood tests in the prognosis of colorectal cancer: A prospective, multicenter study from Hungary.

BackgroundThe focus of this study was to analyze the prognostic value of different combinations of inflammatory and coagulation factors using preoperative blood and to appraise the clinical importance of these biomarkers in colorectal cancer patients.MethodsA prospective, multicenter study included patients undergoing radical colorectal surgery in three county hospitals. Inflammatory and coagulation markers were analyzed preoperatively.ResultsTwo hundred and one patients were included. We examined patients based on their tumor localization. Colon cancer group involved patients with the tumor localized in the colon (n = 105, 52.24%) and rectal cancer group the patients with the tumor in the rectum (n = 96, 47.76%). Examining coagulation factors, univariate Cox analysis of colon cancer patients showed that activated partial thromboplastin time (p = 0.020) was significantly associated with overall survival, but we could not prove it in multivariate analysis. In colon cancer patients, neutrophil‐to‐lymphocyte ratio (NLR, p < 0.001) was positively correlated with tumor size and had significant association (χ 2 = 5.48, p = 0.019, df = 1) with perineural invasion. Univariate and multivariate Cox analysis of colon cancer patients showed that NLR (p = 0.011 and p = 0.048) was significantly associated with disease‐free survival (DFS).ConclusionNLR was proved to be an independent prognostic factor for DFS in patients with non‐metastatic colon cancer. NLR might help to recognize the high‐risk patients between patients with the same tumor‐node‐metastasis stage and could help with the decision on adjuvant chemotherapy. Since the biomarkers in preoperative blood tests are habitually evaluated, NLR could be an inexpensive prognostic marker that can be easily assessed in clinical practice.

Impact of cumulative cisplatin dose in childhood nasopharyngeal carcinoma based on neoadjuvant chemotherapy response in the intensity-modulated radiotherapy era: a real-world study

BackgroundWe aimed to comprehensively investigate the optimal cumulative cisplatin dose during concurrent chemoradiotherapy (CC-CCD) for locoregionally advanced nasopharyngeal carcinoma (CA-LANPC) with different tumor responses after neoadjuvant chemotherapy (NAC).MethodsPatients with CA-LANPC who underwent NAC followed by cisplatin-based concurrent chemoradiotherapy were retrospectively analyzed. Evaluation of tumor response in patients was conducted by Response Evaluation Criteria for Solid Tumor (RECIST) 1.1 after two to four cycles NAC. Multivariate Cox proportional hazards models were used for prognosis. Recursive partitioning analysis (RPA) was conducted to classify participates and predict disease-free survival (DFS).ResultsOne hundred and thirty-two patients with favorable response after NAC were included. The median CC-CCD was 163 mg/m2 (IQR, 145–194 mg/m2), and 160 mg/m2 was selected as the cutoff point to group patients into low and high CC-CCD groups (< 160 vs. ≥ 160 mg/m2). There was significant improvement in 5-year DFS (91.2% vs. 72.6%; P = 0.003) for patients receiving high CC-CCD compared to those receiving low CC-CCD. Multivariate analysis revealed that CC-CCD, T stage, and Epstein–Barr virus (EBV) DNA were independent prognostic factors for DFS (P < 0.05 for all). Patients were further categorized into two prognostic groups by RPA: the low-risk group (T1-3 disease with regardless of EBV DNA, and T4 disease with EBV DNA < 4000 copy/mL), and the high-risk group (T4 disease with EBV DNA ≥ 4000 copy/mL). Significant 5-year DFS improvement was observed for the high-risk group (P = 0.004) with high CC-CCD. However, DFS improvement was relatively insignificant in the low-risk group (P = 0.073).ConclusionsCC-CCD was a positive prognostic factor for responders after NAC in CA-LANPC. Furthermore, CC-CCD ≥ 160 mg/m2 could significantly improve DFS in the high-risk group with CA-LANPC, but the benefit of high CC-CCD in the low-risk group needs further study.

Matrix metalloproteinase‑1 expression is regulated by HIF‑1‑dependent and epigenetic mechanisms and serves a tumor‑suppressive role in gastric cancer progression.

The matrix metalloproteinase (MMP) family is associated with degradation of the extracellular matrix and is known to promote cancer invasion. The present study aimed to investigate the biological role of MMP-1 in gastric cancer cells and analyze the association between MMP-1 expression and the clinical outcomes of gastric cancer patients. In the present study, hypoxia accelerated invasion, accompanied by elevated MMP-1 expression in the gastric cancer cell line 58As9. Additionally, hypoxia-inducible factor-1α (HIF-1α) knock- down in 58As9 cells reduced MMP-1 expression under hypoxic conditions. Treatment with 5-aza-2-deoxycytidine and trichostatin A restored MMP-1 expression in the MMP-1-deficient cell lines MKN45 and MKN74. These results indicated that MMP-1 expression was controlled by both HIF-1α-dependent and epigenetic mechanisms in gastric cancer cell lines. In addition, MMP-1 knockdown impaired the hypoxia-induced invasiveness of 58As9 cells, implicating MMP-1 in the elevated invasion. By contrast, knockdown enhanced the proliferative ability of 58As9 cells, whereby expression of cell cycle-related genes was subsequently altered. In nude mouse models, the knockdown accelerated the growth of xenograft tumor and the development of peritoneal dissemination. In an immunohistochemical study using 161 surgically resected cancer tissues, the Ki67 score was significantly higher in the group with low MMP-1 expression (P<0.001). Disease-free survival (DFS) and disease-specific survival (DSS) were both significantly reduced in patients with low MMP-1 expression (log-rank test; DFS: P=0.005; DSS: P=0.022). Multivariate analysis demonstrated that MMP-1 expression was an independent prognostic factor for DFS and DSS [DFS: HR=2.11 (1.22–3.92) P=0.005, DSS: HR=2.90 (1.23–8.50) P=0.012]. In conclusion, the present study indicated that MMP-1 may serve as a tumor-suppressive factor that inhibits gastric cancer progression, although it promoted invasion in vitro.

Radiomics Analysis of Fat Saturated T2-Weighted MRI Sequences for Prognostic Prediction to Soft-Tissue Sarcoma of the Extremities and Trunk Treated With Neoadjuvant Radiotherapy

Radiomics Analysis of Fat Saturated T2-Weighted MRI Sequences for Prognostic Prediction to Soft-Tissue Sarcoma of the Extremities and Trunk Treated With Neoadjuvant Radiotherapy

Tumor-Infiltrating Lymphocytes and Prognosis in Stage I-III Triple-Negative Breast Cancer: A Retrospective Analysis of 258 Patients Treated Without Neoadjuvant Therapy.

<h3>Purpose/Objective(s)</h3> To investigate the prognostic value of tumor-infiltrating lymphocytes (TIL) in patients with triple-negative breast cancer (TNBC). <h3>Materials/Methods</h3> The clinicopathologic data of 258 patients with I-III stage TNBC treated in one institution from 2010 to 2013 were collected. Two-hundred and twelve patients (82.2%) received mastectomy and 46 (17.8%) received breast-conserving surgery. Eighty-four patients (32.6%) had stage I, 138 (53.5%) had stage II and 36 (14.0%) had stage III disease. All had received adjuvant chemotherapy without neoadjuvant therapy, and 96 (37.2%) received postoperative radiotherapy. The density of TILs with its expression of stromal (s) and intratumoral (i) CD8, FOXP3 (sCD8, iCD8, sFOXP3, iFOXP3) were evaluated by hematoxylin and eosin and immunohistochemical (IHC) staining. An IHC staining for PD-1 and PD-L1 (22C3) were also conducted. Locoregional recurrence (LRR), distant metastasis (DM) and disease-free survival (DFS) and overall survival (OS) rates were calculated by using the Kaplan-Meier method and compared by log-rank test. The association of relapse and survival outcomes with TILs concentration was evaluated using multivariable proportional hazards regression. Optimum cutoff values for sCD8, iCD8, sFOXP3 and iFOXP3 were identified using the maxstat package in R. <h3>Results</h3> At a median follow-up of 80 months (range, 9-111 months), patients with lymphocyte-predominant breast cancer (sTIL ≥60%) had significantly lower 5-year LRR (3.6% vs 15.6%; <i>P</i> = 0.047) and higher DFS (96.4% vs 84.5%; <i>P</i> = 0.025) compared to those with < 60% sTIL. Patients with sCD8 > 10% had significantly lower 5-year LRR (4.2% vs 15.7%, <i>P</i> = 0.010) and DM (2.8% vs 14.6%; <i>P</i> = 006) and higher 5-year DFS (95.8% vs 83.9%, <i>P</i> = 0.015) and OS (97.1% vs 91.2%, <i>P</i> = 0.044) compared to patients with sCD8 ≤10%. Patients with iCD8 > 5% had significantly lower 5-year LRR (2.2% vs 14.8%, <i>P</i> = 0.013) and DM (13.4%, <i>P</i> = 0.021) and higher 5-year DFS (97.8% vs 84.8%, <i>P</i> = 0.008) and OS (97.7 vs 91.7%, <i>P</i> = 0.030) compared to patients with iCD8 ≤5%. Patients with sFOXP3 > 3/HPF also had significantly lower 5-year LRR (4.5% vs 15.0%, <i>P</i> = 0.012) and DM (5.9% vs 13.5%, <i>P</i> = 0.043) and higher 5-year DFS (92.7% vs 85.0%, <i>P</i> = 0.034) and OS (95.6% vs 91.5%, <i>P</i> = 0.047) compared to sFOXP3 ≤3/HPF. However, no survival benefits were found from patients with iFOXP3 > 14/HPF. Presence of PD-1-positive immune cells in TNBC were associated with a significantly better DFS (93.4% vs 83.5%, <i>P</i> = 0.044), while PD-L1 expression had no impact on patient outcomes. Multivariate analysis revealed that sTIL ≥60% (HR 0.23, 95% CI 0.05-0.99, <i>P</i> = 0.048) or PD-1 positivity (HR 0.40, 95% CI: 0.16-0.96, <i>P</i> = 0.041) were independent prognostic factors for DFS, in addition to stage (<i>P</i> < 0.001). No other subsets of TILs nor PD-L1 was independently associated with relapse or survival (all <i>P</i> > 0.05). <h3>Conclusion</h3> High density of stromal TIL and presence of PD-1-positive immune cells may have a positive prognostic value in TNBC. These findings need further validation.

A Nomogram to Predict Disease-Free Survival Following Neoadjuvant Chemotherapy for Triple Negative Breast Cancer.

BackgroundNeoadjuvant chemotherapy (NACT) is considered a standard treatment strategy for locally advanced triple negative breast cancer (TNBC). TNBC patients who achieve a pathologic complete response (pCR) are predicted to have a better prognosis while unfavorable chemo-sensitivity is still associated with a higher risk of disease relapse. The objective of this study was to construct a nomogram to predict disease-free survival (DFS) for TNBC patients following NACT.MethodsA total of 165 TNBC patients who underwent standard NACT and surgery were retrospectively reviewed, and data on their clinicopathological factors before and after NACT were collected. Independent prognostic factors for DFS were identified by Cox regression based on lower Akaike information criteria (AIC) and Bayesian information criterion (BIC). A nomogram to predict the 2-year and 5-year DFS following NACT for TNBC was constructed based on training cohort (n = 132) and validated by a validation cohort (n = 33).ResultsEither limited or full pCR (breast-only pCR, node-only pCR, or both-pCR) indicated significantly improved DFS and overall survival (OS) (p < 0.001). Lager residual tumor size (hazard ratio [HR] 1.175, p = 0.011) and the presence of lymphatic vessel invasion (LVI) (HR 3.168, p = 0.001) were identified as independent predictors of disease relapse in the training cohort. Five variables, including age, primary tumor size, histological grade, residual tumor size, and LVI were used to establish the nomogram. The C-index of the nomogram was 0.815, and calibration curves showed an acceptable consistency between the actual and nomogram-predicted 2-year and 5-year DFS. The proposed nomogram demonstrated superior predictive performance compared with Residual Cancer Burden (RCB) classification and the 8th American Joint Committee on Cancer Post Neoadjuvant Therapy Classification (AJCC ypTNM) staging system (area under the curve [AUC] for 2-year DFS: 0.870 vs. 0.758 vs. 0.711, respectively; AUC for 5-year DFS: 0.794 vs. 0.731 vs. 0.702, respectively) in the validation cohort.ConclusionsThe nomogram proposed in our study enabled to quantify the risk of disease relapse and demonstrated superior predictive performance than a survival predict instrument. It was an easy-to-use tool for clinicians to guide individualized surveillance of TNBC patients following standard NACT.

Preoperative ALBI grade predicts the outcomes in non-B non-C HCC patients undergoing primary curative resection

BackgroundThe albumin–bilirubin (ALBI) grade has been validated as a significant prognostic predictor for hepatocellular carcinoma (HCC). However, there is little information about the ALBI grade in patients with non-B non-C HCC (NBNC-HCC) receiving surgery.AimThis study aimed to evaluate the prognostic significance of the ALBI grade in patients with NBNC-HCC after primary curative resection.MethodFrom January 2010 to April 2016, 2137 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 168 NBNC-HCC patients who received primary curative resection were analyzed. The impacts of the ALBI grade on disease-free survival (DFS) and overall survival (OS) were analyzed by multivariate analysis.ResultsThere were 66 (39.3%), 98 (58.3%), and 4 (2.4%) patients with an ALBI grade of I, II, and III, respectively. Patients with an ALBI grade II/III were older (p = 0.002), more likely to have hypoalbuminemia (p < 0.001), and more commonly had Child–Pugh class B (p = 0.009) than patients with an ALBI grade I. After a median follow-up of 76 months, 74 (44%) patients experienced recurrence, and 72 (42.9%) patients died. Multivariate analysis revealed that alpha-fetoprotein (AFP) > 200 ng/mL (p = 0.021), number of tumors (p = 0.001), and tumor stage (p = 0.007) were independent prognostic factors for DFS. Additionally, AFP > 200 ng/mL (p = 0.002), ALBI grade II/III (p = 0.002), and tumor stage (p < 0.001) were independent risk factors for poor OS.ConclusionThe preoperative ALBI grade can be used to predict mortality in patients with NBNC-HCC after primary curative resection.

Oncologic safety of laparoscopic surgery for women with apparent early-stage uterine serous carcinoma: A multi-institutional retrospective cohort study.

To compare the long-term survival outcomes of patients with apparent early-stage uterine serous carcinoma (USC) who underwent laparoscopic staging surgery with those who underwent open surgical staging. A total of 295 patients from four Chinese teaching hospitals were included. Overall survival (OS) and disease-free survival (DFS) were estimated and compared using the Kaplan-Meier method and the log-rank test among patients after laparoscopic surgery or open surgery. The Cox proportional hazards regression model was applied to adjust for potential confounding factors. For patients with apparent early-stage USC, laparoscopic surgery was associated with deteriorated DFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.15-2.93, P=0.012), and there was no significant difference in OS between the two groups (HR 1.74, 95% CI 0.99-3.08, P=0.056). However, after adjusting for confounding factors, the surgical approach was not an independent prognostic factor for DFS (adjusted HR 1.16, 95% CI 0.63-2.12, P=0.636) and OS (adjusted HR 1.11, 95% CI 0.52-2.38, P=0.794) in apparent early-stage USC. For apparent early-stage USC, laparoscopic surgery is safe. This needs to be confirmed by future prospective clinical trials.

Clinical features and prognostic factors for early-stage external auditory canal carcinoma

Objective:To analyze the clinical features and the prognostic factors of early-stage external auditory canal carcinoma. Methods:Data from 36 patients with early-stage external auditory canal carcinoma（T1, T2） treated in Department of Otolaryngology, Xijing Hospital, Air Force Military Medical University from January 2008 to June 2020 were reviewed retrospectively, including clinical manifestations, surgical and treatment methods, pathological types and disease status. The relationship between survival rate and the prognostic factors was compared using Kaplan-Meier method, and the independent risk factors were analyzed by Cox proportional hazards model. Results:There were 36 patents with early-stage external auditory canal carcinoma. The common initial symptoms were otalgia（66.7%）, otorrhea（41.7%） and hearing loss（30.6%）. The most common histopathologic types were adenoid cystic carcinoma（50.0%） and squamous cell carcinoma（33.3%）. Among the patients, 21 patients（58.3%） were initially treated, 9 patients（25.0%） were treated with salvage therapy, and 6 patients（16.7%） were re-surgery after recurrence. The 5-year disease-specific survival（DSS）, disease-free survival（DFS） and relapse-free survival（RFS） were 82.3%, 64.0% and 73.0% respectively. Seven cases （19.4%） relapsed after surgery. For 5-year survival rate, the lateral temporal bone resection with superficial parotidectomy（DSS 91.7%, DFS 83.9%） is higher than the lateral temporal bone resection only（DSS 77.8%, DFS 55.6%） and sleeve resection（DSS 75.0%, DFS 56.0%）, but there was no significant difference（P>0.05）. In these patients, the postoperative radiotherapy and disease status had no significant impact on the survival rate. Additionally, there was no obvious correlation between recurrence and age, gender, stage, histopathologic types, operation methods and postoperative radiotherapy（P>0.05）. But there were significant differences between histopathologic types and DSS or DFS（P<0.05）. Multivariate regression analysis showed that histopathologic type was an independent prognostic factor for DFS. Conclusion:There are no specific clinical manifestations for early-stage external auditory canal carcinoma, such as otalgia and otorrhea. Histopathologic types have a direct impact on the patients'prognosis. Thus, individualized treatment should be applied based on pathologic findings to improve the survival rate.

243 PROGNOSTIC IMPACT OF CXCR7 AND CXCL12 EXPRESSION IN PATIENTS WITH ESOPHAGEAL ADENOCARCINOMA

Abstract Chemokines are major regulators of cell trafficking and adhesion. The chemokine CXCL12 and its receptors, CXCR4 and CXCR7, have recently been reported as biomarkers in various cancers, including esophageal squamous cell carcinoma; however, there are few studies of these chemokines in esophageal adenocarcinoma (EAC). In this study, we investigated the relationship between expression of CXCL12, CXCR4 and CXCR7, and prognosis in patients with EAC. Methods This study examined 55 patients with EAC who were treated in Toronto General Hospital from 2001 to 2010. Tissue microarray immunohistochemistry was used to evaluate the expression of CXCL12, CXCR4 and CXCR7. Evaluation of immunohistochemistry was performed by a pathologist without knowledge of patients’ information and scored based on a semiquantitative scoring system. The average score from multiple cancer tissues on the microarray was utilized and patients were divided into high or low expression groups using the median score as a cutoff point. These results were compared with the patients’ clinicopathological features and survival. Results The score of CXCR7 was positively correlated with that of CXCL12 (r = 0.3154). High CXCR7 expression was significantly associated with lymphatic invasion (present vs absent, P = 0.005), higher number of lymph node metastases (pN0–1 vs pN2–3, P = 0.0014) and TNM stage (Stage I-II vs III-IV, P = 0.0168). Patients with high CXCR7 (n = 23) expression was associated with worse overall (OS) and disease-free survival (DFS) (P = 0.0221, 0.0090, respectively), and patients with high CXCL12 (n = 24) tended to have worse OS and DFS (P = 0.1091, 0.1477, respectively). High expression of both CXCR7 and CXCL12 was an independent prognostic factor for DFS on multivariable analysis (HR0.3, 95%CI: 0.1–0.8, P = 0.0115). Conclusion High CXCR7 expression was associated with poor prognosis in patients with EAC, and high expression of CXCR7 and its ligand CXCL12, had a stronger association on prognosis. Further study of this potential biomarker using whole tissue samples and larger sample size is warranted.

Prognostic Value of NLRP3 Inflammasome and TLR4 Expression in Breast Cancer Patients.

Inflammasome complexes play a pivotal role in different cancer types. NOD-like receptor protein 3 (NLRP3) inflammasome is one of the most well-studied inflammasomes. Activation of the NLRP3 inflammasome induces abnormal secretion of soluble cytokines, generating advantageous inflammatory surroundings that support tumor growth. The expression levels of the NLRP3, PYCARD and TLR4 were determined by immunohistochemistry in a cohort of primary invasive breast carcinomas (BCs). We observed different NLRP3 and PYCARD expressions in non-tumor vs tumor areas (p<0.0001). All the proteins were associated to more aggressive clinicopathological characteristics (tumor size, grade, tumor proliferative activity etc.). Univariate analyses were carried out and related Kaplan-Meier curves plotted for NLRP3, PYCARD and TLR4 expression. Patients with higher NLRP3 and TLR4 expression had worse 5-year disease-free survival (DFS) compared to patients with lower NLRP3 and TLR4 expression (p =0.021 and p = 0.009, respectively). In multivariate analysis, TLR4 was confirmed as independent prognostic factors for DFS (HR = 2.03, 95% CI 1.16–3.57, p = 0.014), and high NLRP3 expression showed a slight association with DFS (HR = 1.75, 95% CI 0.98–3.15, p = 0.06). In conclusion, we showed TLR4 expression as independent prognostic factors and we highlighted for the first time that high expression of NLRP3 is linked to a poor prognosis in BC patients. These results suggest that NLRP3 and TLR4 could be two new good prognostic factor for BC patients.

Prognostic Role of Lymphovascular Invasion in Patients with Early Breast Cancer.

In this study, our aim was to evaluate the role of lymphovascular invasion (LVI) in the prognosis of patients with early stage breast cancer. The medical records of more than 7000 patients who suffered from invasive breast cancer and had undergone surgical treatment since December 1994 till December 2019, retrospectively. Patient's history, physical examination and the clinicopathological features, histopathology characteristics, immunohistochemical findings, adjuvant systemic therapy, recurrence rate, metastasis-free survival (MFS), disease-free survival (DFS), and overall survival (OS) were reviewed. A total of 5425 eligible patients were categorized into two groups based on the presence of LVI; 3031 (55.9%) patients had no LVI (group 1) and LVI was present in 2394 (44.1%) patients (group 2), then divided into LN-positive and -negative groups. Presence of LVI was significantly associated with patient age ≤ 40years (p = 0.048), high histological grade (grades II and III, p < 0.001), tumor size between 2-5cm and > 5cm (p < 0.001), number of involved LN ≥ 4 (p < 0.001), and negative ER (p = 0.042) tumors. Five-year OS, MFS, and DFS were 93%, 88.9%, and 76.1% and 85.2%, 84.7%, and 73.6 in groups 1 and 2, respectively (P < 0.001). On multivariate analysis, LVI was an independent prognostic factor for DFS in all patients. Furthermore, histological grade II, histological grade III, and a higher number of involved LNs (≥ 4) were independent predictors in all patients. Thus, the presence of LVI can be considered as an independent prognostic factor for patients with operable breast cancer, irrespective of the LN status.

The Prognostic Role of PORT and EGFR Mutation Status in Completely Resected Stage IIIA/N2 Non-Small Cell Lung Cancer Patients with Postoperative Chemotherapy.

Background: The treatment choice for completely resected stage IIIA/N2 non-small cell lung cancer (NSCLC) patients is still controversial now. Our study aims to identify potential prognostic factors in stage IIIA/N2 NSCLC patients with complete surgical resection and postoperative chemotherapy.Methods: In this study, we screened the stage IIIA/N2 NSCLC patients diagnosed in the Affiliated Cancer Hospital of Zhengzhou University from 2015 to 2019. Completely resected patients with postoperative chemotherapy (PCT) were enrolled. The univariate and multivariate COX proportional hazards regression analyses were used to identify the prognostic factors. The Kaplan-Meier survival curve was used to compare the disease-free survival (DFS) and overall survival (OS) in the subgroup analyses.Results: 180 patients were collected, including 142 patients with PCT treatment alone and 38 patients with postoperative radiotherapy (PORT) treatment. The median DFS was 17.8 months (95% CI: 16.5–19.1 months) and the median OS was 50.6 months (47.4–53.9 months) in all the patients. The median DFS of the PORT group was significantly longer than the PCT group (38.7 vs 16.7 months, p < 0.001). Epidermal growth factor receptor (EGFR) mutation-positive patients had a worse DFS compared with EGFR mutation-negative patients (16.8 vs 18.0 months, p = 0.032). Possible prognostic factors were evaluated through univariate COX regression analysis. The further multivariate COX regression analysis showed that patients with PORT (HR: 0.318, 95% CI: 0.185–0.547, p < 0.001), EGFR mutation-negative (HR: 0.678, 95% CI: 0.492–0.990, p = 0.044), T1 (HR: 0.661, 95% CI: 0.472–0.925, p = 0.016), and lobectomy (HR: 0.423, 95% CI: 0.191–0.935, p = 0.034), had better DFS. The only independent prognostic factor of OS was the type of surgery (p = 0.013).Conclusion: PORT might improve the DFS of stage IIIA/N2 NSCLC patients with complete surgical resection and PCT, but it cannot increase OS. Besides, EGFR mutation status, T stage, and type of surgery are possible independent prognostic factors for DFS, and type of surgery is associated with OS. These factors remain to be clarified in further studies.