Independent Prognostic Factor For Disease-free Survival Research Articles

Clear cell hepatocellular carcinoma: Gd-EOB-DTPA-enhanced MR imaging features and prognosis.

To investigate imaging findings on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) and prognosis of clear cell hepatocellular carcinoma (CCHCC) comparing with non-otherwise specified hepatocellular carcinoma (NOS-HCC). The clinical, pathological and MR imaging features of 42 patients with CCHCC and 84 age-matched patients with NOS-HCC were retrospectively analyzed from January 2015 to October 2021. Univariate and multivariate logistic regression and Cox regression analyses were performed to identify independent diagnostic and prognostic factors for CCHCC. Disease-free survival (DFS) and overall survival (OS) were determined by Kaplan-Meier analysis. CCHCC showed fat content more frequently (P < 0.001) and relatively higher Edmondson tumor grade (P = 0.001) compared with NOS-HCC. The lesion-to-muscle ratio (LMR) and lesion-to-liver ratio (LLR) of CCHCC on pre-enhancement T1-weighted imaging (pre-T1WI) (P = 0.001, P = 0.003) and hepatobiliary phase (HBP) (P = 0.007, P = 0.048) were significantly higher than those of NOS-HCC. The area under the curve (AUC) for fat content, LLR on pre-T1WI and their combination with better diagnostic performance in predicting CCHCC were 0.678, 0.666, and 0.750, respectively. There was no statistically significant difference in clinical outcomes between CCHCC and NOS-HCC. Multivariate Cox analysis confirmed that tumor size > 2cm and enhancing capsule were independent prognostic factors for DFS and OS among CCHCC patients. Fat content and adjusted lesion signal intensity on pre-T1WI and HBP could be used to differentiate CCHCC from NOS-HCC. CCHCC had similar prognosis with NOS-HCC.

The Effect of Age on Pancreaticoduodenectomy; Comorbidities, Short-term Outcomes, and Survival.

To evaluate the complications, mortality, and survival rates of patients aged >70 years undergoing pancreaticoduodenectomy, and to determine associated risk factors. Descriptive study. Place and Duration of the Study: General Surgery Clinic of Eskişehir Osmangazi University Medical Faculty Hospital, Eskişehir, Turkiye, from January 2014 to September 2020. A retrospective scrutiny of 94 patients who had undergone pancreaticodueodenectomy, was carried out. The patients were separated into two age groups of younger and older than 70 years, and were compared in respect of clinicopathological characteristics, comorbidities, perioperative characteristics, and complications. Independent risk factors for the endpoints of perioperative mortality and survival were investigated. No significant difference was determined between the groups in respect of biochemical values, and perioperative and histochemical characteristics. Comorbidities were present at a higher rate in the older patients (77.8% vs. 38.8%, p<0.001). The postoperative complication rates were similar (33.3% vs. 32.7%, p=0.944). Perioperative mortality (first 30 days) was determined at a significantly higher rate in the older age group (20.0% vs. 4.1%, p=0.016). The age of patients >70 years increased the risk of mortality 4.851-fold but was not an independent predictive factor (p=0.086). The groups were similar in respect of disease-free survival (DFS) and overall survival (OS, Log-rank p=0.780, p=0.386). Age [Hazard Ratio (HR): 1.029, p=0.048] and pancreas adenocarcinoma (HR: 1.846, p=0.028) were determined to be independent prognostic factors for DFS, and pancreas adenocarcinoma (HR 1.940, p=0.023) for OS. Older age was not seen to change survival in patients undergoing pancreaticoduodenectomy, but mortality within the first 30 days was affected. Age is not accepted as an absolute contraindication. It is recommended that pancreaticoduodenectomy is performed on patients aged >70 years with careful patient selection, prudent preoperative preparation, a meticulous surgical technique, and close multidisciplinary postoperative support. Pancreaticoduodenectomy, Elderly, Comorbidity, Complication, Mortality, Survival.

Platinum-based neoadjuvant chemotherapy upregulates STING/IFN pathway expression and promotes TILs infiltration in NSCLC.

To evaluate the effects of platinum-based neoadjuvant chemotherapy (NACT) on the STING/IFN pathway and tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC), as well as clinicopathological factors affecting patient survival. A total of 68 patients aged 34-77 years with NSCLC who received neoadjuvant chemotherapy and surgical treatment from March 2012 to February 2019 were reviewed, and the clinical pathological data and paired tissue specimens before and after NACT were collected. Immunohistochemistry and immunofluorescence were used to detect the protein levels of STING, PD-L1 and IFN-β, and the infiltration density of CD3+ TILs and CD8+TILs. The correlation between the expression of STING, PD-L1, IFN-β and the infiltration density of CD3+ TILs and CD8+ TILs as well as the clinicopathological characteristics before and after NACT was analyzed. The relationship between the related indexes, clinicopathological features and prognosis was also discussed. NACT increased the expression of STING, IFN-β and PD-L1 in tumor cells, and the infiltration of CD3+ and CD8+ TILs. In addition, ypTNM stage, ypN stage, changes in CD3+ TILs and in PD-L1 were associated with DFS (disease-free survival). CD3+ TILs changes and ypN stage were associated with OS (overall survival). Notably, ypN stage and CD3+ TILs changes were independent prognostic factors for DFS and OS. NACT stimulates STING/IFN-β pathway, promotes infiltration of CD3+ and CD8+ TILs, triggers innate and adaptive immunity, and also upregulates PD-L1, which complemented the rationale for neoadjuvant chemotherapy in combination with immunotherapy. In addition, DFS was longer in patients with ypTNM I, ypN0-1, and elevated CD3+TILs after NACT. Patients with ypN0 and elevated CD3+ TILs after NACT had better OS benefits.

Treatment patterns and clinical outcomes of patients with resectable non–small cell lung cancer receiving neoadjuvant immunochemotherapy: A large-scale, multicenter, real-world study (NeoR-World)

BackgroundNeoadjuvant immunotherapy has ushered in a new era of perioperative treatment for resectable non–small cell lung cancer (NSCLC). However, large-scale data for verifying the efficacy and optimizing the therapeutic strategies of neoadjuvant immunochemotherapy in routine clinical practice are scarce. MethodsNeoR-World (NCT05974007) was a multicenter, retrospective cohort study involving patients who received neoadjuvant immunotherapy plus chemotherapy or chemotherapy alone in routine clinical practice from 11 medical centers in China between January 2010 and March 2022. Propensity score matching was performed to address indication bias. ResultsA total of 408 patients receiving neoadjuvant immunochemotherapy and 684 patients receiving neoadjuvant chemotherapy were included. The pathologic complete response (pCR) and major pathologic response (MPR) rates of the real-world neoadjuvant immunochemotherapy cohort were 32.8% and 58.1%, respectively. Notably, patients with squamous cell carcinoma exhibited significantly higher pCR and MPR rates than those with adenocarcinoma (pCR, 39.2% vs 16.5% [P < .001]; MPR, 66.6% vs 36.5% [P < .001]), whereas pCR and MPR rates were comparable among patients receiving different neoadjuvant cycles. In addition, the 2-year rates of disease-free survival (DFS) and overall survival (OS) rate were 82.0% and 93.1%, respectively. Multivariate analyses identified adjuvant therapy as an independent prognostic factor for DFS (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.89; P = .018) and OS (HR, 0.28; 95% CI, 0.13-0.58; P < .001). A significantly longer DFS with adjuvant therapy was observed in patients with non-pCR or 2 neoadjuvant cycles. We observed significant benefits in pCR rate (32.4% vs 6.4%; P < .001), DFS (HR, 0.50; 95% CI, 0.38-0.68; P < .001) and OS (HR, 0.61; 95% CI, 0.40-0.94; P = .024) with immunotherapy plus chemotherapy compared to chemotherapy alone both in the primary propensity-matched cohort and across most key subgroups. ConclusionsThe study validates the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy alone for NSCLC. Adjuvant therapy could prolong DFS in patients receiving neoadjuvant immunochemotherapy, and patients with non-pCR or those who underwent 2 neoadjuvant cycles were identified as potential beneficiaries of adjuvant therapy.

The impact of neo/adjuvant treatment choices on prognosis for surgically treated small-cell neuroendocrine carcinoma of the cervix.

Small-cell neuroendocrine carcinoma of the cervix (SCNCC) is a rare and aggressive tumor with a poor prognosis. Surgical resection followed by adjuvant therapy is the standard treatment for early-stage disease but the influence of different neo/adjuvant treatment approaches remains unclear. Retrospectively, we collected patients' characteristics and treatments in two medical centers. Disease status and survival outcomes were renewed through follow-up. Statistics analysis mainly included Kaplan-Meier methods for survival curve estimation, log-rank test for survival curve comparison, and Cox proportional hazards models for independent prognostic factors prediction. Finally, 51 patients treated by radical surgery between January 2010 and April 2020 were enrolled with a median age of 50 years (range: 32-68). 12 (23.5%) patients were at stage IIIC1 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging systems and the rest were at the early stage. The mean tumor size was 3.6±1.3 cm. Pathological examination found 24 cases with pure SCNCC and 27 cases with admixed SCCC. 29 (56.9%) patients had deep stromal infiltration and 19 (37.3%) patients had lymphovascular space invasion. 34 (66.7%) patients received neo/adjuvant chemotherapy and pelvic radiation was conducted in 41 (80.39%) patients with a median dose of 46 Gy (range: 40-50.4 Gy). The median follow-up time was 25.0 months. The median disease-free survival (DFS) time was 23.0 months. 27 (52.9%) patients developed distant metastasis and 14 (27.5%) experienced local failure. The median overall survival (OS) was 32.0 months. Univariate and multivariate analysis showed neoadjuvant chemotherapy as negative (HR=2.081, 95% CI 1.030-4.203, p=0.041) and adjuvant chemotherapy (HR=0.409, 95% CI 0.213-0.784, p=0.020) as positive independent prognostic factor for DFS. For OS, only lymph node metastasis was confirmed as an independent prognostic factor in both univariate analysis (HR=1.528, 95% CI 1.011-2.308, p=0.044) and multivariate analysis (HR=1.697, 95% CI 1.041-2.768, p=0.034). In conclusion, for surgically treated SCNCC, adjuvant chemotherapy showed a positive influence on DFS while neoadjuvant chemotherapy harmed DFS. OS was unaffected by either treatment choice.

The role of insulinoma-associated protein 1 in predicting the progression and prognosis of human olfactory neuroblastoma in China

ObjectiveRecent studies have suggested that insulinoma-associated protein 1 (INSM1) is a useful marker for pathological diagnosis of neuroendocrine tumors. In the present study, we investigated the association between INSM1 expression and prognosis in patients with olfactory neuroblastoma (ONB) and assessed the usefulness of INSM1 as a prognostic biomarker in these patients. MethodImmunohistochemistry was performed on 109 ONB patients who underwent endoscopic surgery at Beijing Tong Ren Hospital (Beijing, China) between June 2006 and November 2021 Patient age at the time of surgery ranged from 10 months to 72 years (mean age, 43.55 ± 13.47 years). In total, 63 (57.8%) and 46 (42.2%) tumors occurred in male and female patients, respectively. The percentages of grade I–IV cases were 13.8% (15/109), 36.7% (40/109), 29.4% (32/109) and 20.2% (22/109), respectively. ResultsThe expression rate (moderately/strongly positive) of INSM1 was significantly higher in high-grade (Ⅲ/Ⅳ; 83%; 45/54) than low-grade (Ⅰ/Ⅱ; 27%; 15/55) ONB cases. High expression levels of INSM1 were significantly positively associated with high pathological stage (p < 0.001), local recurrence, and death. Kaplan‑Meier analysis revealed that patients with high INSM1 expression had significantly shorter disease‑free survival (DFS) and mean survival (75.01 ± 10.71 vs. 158.56 ± 10.32) times, and shorter overall survival (OS). Multivariate Cox regression analysis revealed that INSM1 was an independent prognostic factor for DFS (HR: 4.963, 95%CI [2.11–10.84] p < 0.001) and OS (HR: 4.791, 95%CI [2.117–10.485], p < 0.001) after adjusting for sex, age, and tumor grade. In addition, INSM1 was an independent prognostic factor for DFS in patients treated with surgery (HR: 3.714, 95%CI [1.267–10.889], p = 0.017) and chemotherapy (HR: 5.574, 95%CI [1.584–19.612], p = 0.007). ConclusionINSM1 expression had a positive association with the prognosis of patients with ONB and could serve as a prognostic biomarker in these patients.

Clinical value of folate receptor-positive circulating tumor cells in patients with esophageal squamous cell carcinomas: a retrospective study

BackgroundThe aim of the study is to explore the role of preoperative folate receptor-positive circulating tumor cell (FR+CTC) levels in predicting disease-free survival (DFS) and overall survival (OS) in patients with esophageal squamous cell carcinomas (ESCC).MethodsThree ml blood samples were prospectively drawn from ESCC patients, and ligand-targeted polymerase chain reaction (LT-PCR) was used for the quantification of FR+CTCs. Other serum indicators were measured by traditional methods. Clinicopathological characteristics were obtained from the hospital medical record system, DFS and OS data were obtained by follow-up. The correlation between clinico-pathological characteristics, DFS, and OS and FR+CTCs were analyzed, respectively. Risk factors potentially affecting DFS and OS were explored by Cox regression analysis.Resultsthere were no significant correlations between FR+CTCs and patient age, sex, albumin, pre-albumin, C-reactive protein (CRP), ferritin and CRP/Albumin ratio, tumor size, grade of differentiation, lymph node metastasis, TNM stage, perineural invasion/vessel invasion (all P > 0.05). Nevertheless, preoperative FR+CTCs were an independent prognostic factor for DFS (HR 2.7; 95% CI 1.31-, P = 0.007) and OS (HR 3.37; 95% CI 1.06-, P = 0.04). DFS was significantly shorter for patients with post-operative FR+CTCs ≥ 17.42 FU/3ml compared with patients < 17.42 FU/3ml (P = 0.0012). For OS, it was shorter for patients with FR+CTCs ≥ 17.42 FU/3ml compared with patients < 17.42 FU/3ml, however, the difference did not reach statistical significance (P = 0.51).ConclusionsESCC patients with high FR+CTCs tend to have a worse prognosis. FR+CTCs may monitor the recurrence of cancers in time, accurately assess patient prognosis, and guide clinical decision-making.Trial registrationThe study was approved by the Sichuan Cancer Hospital & Institute Ethics Committee (No. SCCHEC-02-2022-050).

The prognostic role of the change in albumin-derived neutrophil-to-lymphocyte ratio during neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.

The prognosis of patients with locally advanced rectal cancer (LARC) has improved with the adoption of a multidisciplinary treatment approach combining neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME). Developing real-time, sensitive biomarkers to monitor systemic changes during nCRT is of paramount importance. Although the association between albumin-derived neutrophil-to-lymphocyte ratio (Alb-dNLR) and prognosis in various cancers is established, its prognostic value in LARC patients undergoing nCRT is not well-studied. This study enrolled a cohort of 618 LARC patients, stratifying them into two groups according to their change in Alb-dNLR (∆Alb-dNLR) values, using an optimal cut-off point: a low ∆Alb-dNLR group (≤ 0.90) and a high ∆Alb-dNLR group (> 0.90). The prognostic significance of ∆Alb-dNLR was evaluated using a Cox proportional hazards model. The 5-year overall survival (OS) rates were 75.2% in the low ∆Alb-dNLR group (≤ 0.90) and 85.9% in the high ∆Alb-dNLR group (> 90) (P < 0.001). The 5-year disease-free survival (DFS) rates were 71.2% and 80.6%, respectively (P = 0.016). Multivariate analyses demonstrated that both ∆Alb-dNLR and pre-Alb-dNLR were independent prognostic factors for OS (P ≤ 0.001), while ∆Alb-dNLR was demonstrated as an independent prognostic factor for DFS (P = 0.016). A predictive nomogram, incorporating the ∆Alb-dNLR subgroup, demonstrated enhanced performance (concordance index [C-index] of 0.720 for OS and 0.690 for DFS) compared to the pre-treatment Alb-dNLR subgroup (C-index of 0.700 for OS and of 0.680 for DFS). Therefore, ∆Alb-dNLR shows significant potential as a usable and prognostic biomarker for predicting OS and DFS in LARC patients undergoing nCRT.

Novel predictive nomograms based on aspartate aminotransferase‑to‑platelet ratio index for hepatocellular carcinoma with post‑operative adjuvant transarterial chemoembolization.

The clinical significance of systemic inflammation assessed with laboratory analysis of blood samples has been validated in a variety of cancers. The present study was conducted to investigate prognostic significance of preoperative aspartate aminotransferase-to-platelet ratio index (APRI) for the outcome of hepatocellular carcinoma (HCC) patients receiving post-operative adjuvant transarterial chemoembolization (PATACE). A total of 201 patients who underwent PATACE were retrospectively analyzed. A nomogram for HCC was developed using predictors based on multivariate Cox models, and bootstrapping was performed for validation. According to the ROC curve, which was used to divide patients into two cohorts: High APRI group (APRI>1.02) and Low APRI group (APRI≤1.02). In subgroup survival analysis, patients with a relatively low APRI had significantly longer disease-free survival (DFS) and overall survival (OS) than patients with a relatively high APRI, regardless of Barcelona Clinic Liver Cancer (BCLC) stages (BCLC 0/A or BCLC B/C, both P<0.05); while in China liver cancer staging I/II and TNM I/II stage patients, relatively low APRI was associated with improved DFS and OS (both P<0.05). Multivariate Cox models demonstrated that APRI and BCLC stages were independent prognostic factors of DFS and OS (both P<0.05). Nomograms for DFS and OS were constructed, respectively. Calibration curve analysis showed that the standard curve fitted well with the predicted curve. Time-receiver operating characteristic curve analysis revealed that the nomogram had high efficiency. Decision curve analysis demonstrated the high clinical value of the nomogram. APRI is an independent prognostic factor of DFS and OS in HCC patients receiving PATACE, and the combination of APRI with the HCC staging system can refine risk stratification to provide a more accurate prognostic assessment for the outcome of patients receiving PATACE.

Prognostic factors in patients with high-risk stage II colon cancer after curative resection: a post hoc analysis of the JFMC46-1201 trial

PurposeThe goal of the current study was to identify prognostic factors for disease-free survival (DFS) and overall survival (OS) in high-risk stage II colon cancer.MethodsThe subjects were patients with histologically confirmed stage II colon cancer undergoing R0 resection who met at least one of the following criteria: T4, perforation/penetration, poorly differentiated adenocarcinoma, mucinous carcinoma, and < 12 examined lymph nodes. Patients self-selected surgery alone or a 6-month oral uracil and tegafur plus leucovorin (UFT/LV) regimen. Serum CEA mRNA at ≥ 24 h after surgery and < 2 weeks after registration was also examined as a potential prognostic factor for stage II colon cancer. This study is registered with UMIN-CTR (protocol ID: UMIN000007783).Results1880 were included in the analysis to identify prognostic factors for DFS and OS in patients with high-risk stage II colon cancer. In multivariate analyses, gender, depth of tumor invasion, extent of lymph node dissection, number of examined lymph nodes, and postoperative adjuvant chemotherapy (POAC) emerged as significant independent prognostic factors for DFS. Similarly, multivariate analysis showed that age, gender, depth of tumor invasion, perforation/penetration, extent of lymph node dissection, number of examined lymph nodes, and POAC were significant independent prognostic factors for OS. Univariate analyses showed no significant difference in DFS or OS for CEA mRNA-positive and mRNA-negative cases.ConclusionThis study showed that gender, depth of tumor invasion, extent of lymph node dissection, number of examined lymph nodes, and lack of use of POAC were significant independent prognostic factors in stage II colon cancer.

Predictive value of platelet-to-lymphocyte ratio combined with CA199 levels in postoperative survival of patients with gastric cancer: A retrospective study

ObjectiveTo develop a new scoring system based on platelet-to-lymphocyte ratio (PLR) and CA199 to predict the prognosis of gastric cancer. MethodsPLR-CA199 was identified in a retrospective study that was conducted in a training cohort of 990 gastric cancer patients who underwent curable resection from 2012 to 2014 and validated in a validation cohort of 625 patients between 2015 and 2016. ResultsIn the training cohort, PLR-CA199 was related to gender (P = 0.041), age (P = 0.014), tumor location (P = 0.015), tumor size (P < 0.001), Bormann type (P < 0.001), vascular invasion (P < 0.001), perineural invasion (P < 0.001), and TNM staging (P < 0.001). In the validation cohort, PLR-CA199 was related to tumor size (P < 0.001), Bormann type (P = 0.007), vascular invasion (P < 0.001), perineural invasion (P < 0.001), and TNM staging (P < 0.001). Survival analysis showed that in the training cohort the mean disease-free survival (DFS) was 70.699 months for patients PLR-CA199 = 0, 51.223 months for patients PLR-CA199 = 1, and 32.152 months for patients PLR-CA199 = 2 (P < 0.001). The correlation between PLR-CA199 and DFS was further confirmed in the validation cohort (50.640 vs. 41.842 vs. 22.382, P < 0.001). Survival analysis showed that the mean disease special survival (DSS) was 76.668 months for patients PLR-CA199 = 0, 61.218 months for patients PLR-CA199 = 1, and 44.665 months for patients PLR-CA199 = 2 in the training cohort (P < 0.001). The correlation between PLR-CA199 and DSS was further confirmed in the validation cohort (53.858 vs. 46.385 vs. 44.665, P < 0.001). Furthermore, univariate and multivariate analyses showed that PLR-CA199 was an independent prognostic factor for DFS and DSS. ConclusionsPreoperative PLR-CA199 may be a useful prognostic indicator, and is a promising tool for predicting the prognosis for gastric cancer.

The Effect of Clinical (Anatomical) and Prognostic Stage Groups on Survival in Patients Diagnosed with Breast Cancer: MULTI-Center Study Results, TROD Breast Cancer Study Group

The American Joint Committee on Cancer (AJCC) anatomic stage groups have arguably been the most powerful method in predicting breast cancer outcomes. In the present study, we aimed to determine the differences between anatomical stage and clinical prognostic stage groups, which were obtained by adding biological markers such as histologic tumor grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 status to patients diagnosed with breast cancer, the rate of change in stage, and the effect of stage change on survival. The study protocol was sent to all radiation oncology centers in Türkiye. Four centers enrolled their patients to the study. A total of 1470 stage I-III breast cancer patients with complete information on biological markers (histologic tumor grade, hormone receptor, and c-erb B2 receptor status), haven't been treated with neoadjuvant therapy were included to the study and evaluated retrospectively. The 8th edition of AJCC consolidated biological markers in to clinical prognostic stage groups. Kaplan-Meier curves were used to estimate survival. The log-rank test was used to compare the difference between groups. The Cox proportional-hazards regression model was used to determine the association between anatomic-prognostic stage, disease-free survival (DFS), and overall survival (OS). The median follow-up time was 82 (6-237) months. Median age of the patients was 52 years (20-88) and 865 cases (58.8%) were in the postmenopausal period. The axillary lymph node status was negative (N0) in 765 patients (52.1%). Tumor grade was grade I in 200 patients (13.6%), grade II in 812 patients (55.2%) and grade III in 452 patients (30.7%). Estrogen receptor status was positive in 1247 patients (84.8%), PR status was positive in 1178 patients and Her2-neu status was positive in 207 patients (14.1%). A stage change has been identified in a total of 777 patients (52.9%). Compared with the anatomic stage groups, application of the clinical prognostic stage groups assigned 46.4% cases lower and 6.5% cases higher stage. Five- and ten-year OS and DFS rates of the patients are 73.7%, 44.3% and 91.9%, 86.3% respectively. Age (p<0.001), tumor grade (p<0.001), ER status (p<0.001), PR status (p<0.001), cerbB2 receptor status (p = 0.025) were found to be statistically significant variables in multivariable analysis for OS. For DFS, multivariable analysis showed that age (p = 0.027), tumor grade (p = 0.005), anatomical stage (p<0.001) and assigned to higher stage (p = .001) were statistically significant variables. Hormone receptors and c-erb B2 receptor status are independent variables which impact OS and DFS in our patient group which is mostly consisted of early-stage cases according to anatomical stage. In prognostic staging, upstaging stands out as an independent prognostic factor for DFS. The 8th edition of AJCC prognostic stage groups determines the prognosis much better in our patient cohort.

Prognostic Role and Time Varying Failure Hazard of Neoadjuvant Rectal (NAR) Scores in the Stellar Randomized Phase 3 Trial

This study examined the prognostic role of the neoadjuvant rectal (NAR) score on disease-free survival (DFS) in the STELLAR phase III trial and assessed time-varying failure hazard. The study included patients from the STELLAR trial who underwent total mesorecta excision and had calculable NAR scores. Chi-square tests were used to analyze the distribution of demographic information, treatment information, and NAR scores. Kaplan-Meier and Cox regression analyses assessed DFS, while smoothed hazard plots evaluated hazard variations. Of 461 patients, 231 received total neoadjuvant therapy (TNT) and 229 received concurrent chemoradiotherapy (CRT). With a median follow-up of 37 months, 3-year DFS rates for low, intermediate, and high NAR scores were 86.2%, 72.671.8%, and 53.153.6%, respectively (P <0.001). In the TNT group, rates for the corresponding NAR score groups were 87.3%, 67.6%, and 52.4% while in the CRT group, rates were 84.7%, 76.0%, and 53.4% (both P <0.001). Multivariate analysis showed NAR scores as independent prognostic factors for DFS (intermediate vs. low, hazard ratio (HR) = 2.452.55, 95% confidence interval (CI): 1.347 - 4.4675, P <0.003; high vs. low, HR = 4.2668, 95% CI: 2.5133 - 8.727.79, P <0.001). The DFS hazardrisk rates for different NAR score groups initially increased and then decreased, peaking in the second year with rates of 5.04.6%, 11.62%, and 21.52% for low, intermediate, and high NAR scores, respectively. After the fourth year, the high NAR score still had a higher failure hazardrisk (12.5%), while the intermediate and low NAR score had a lower relapse hazardrisk (<3%). The NAR score was a strong prognostic factor for DFS in the STELLAR trial, irrespective of TNT or CRT modalities. Hazard variations at different NAR score levels offer insights for personalized monitoring and warrant further investigation in clinical trials using NAR scores as endpoints. (NCT02533271).

Effect of extracapsular lymph node involvement on the prognosis of patients with esophageal squamous cell carcinoma.

According to the eighth edition of the tumor node metastasis (TNM) staging system for esophageal cancer, it is recommended that extracapsular lymph node involvement (EC-LNI) is included as a registered independent variable for the disease. However, its role in the prognosis has not been clearly explained. To study the value of EC-LNI in the prognosis of esophageal cancer and attempt to explore its molecular mechanism via an enrichment analysis. A retrospective analysis was performed on 544 patients with esophageal squamous cell carcinoma (ESCC) who underwent radical surgery in the department of thoracic surgery of our hospital, focusing on the relationship between EC-LNI and clinicopathological characteristics and its effect on prognosis. Additionally, the mechanism of EC-LNI in esophageal cancer was explored. Among the 271 patients with lymph node metastasis, 125 were EC-LNI (+). The degrees of tumor differentiation, location, TNM stage, vascular tumor thrombus, and nerve invasion were related to the occurrence of EC-LNI. The stage of TNM was considered an independent risk factor for the development of EC-LNI. A significant difference was found in terms of overall survival (OS) and disease-free survival (DFS) between the EC-LNI (+) and EC-LNI (-) groups. A univariate analysis showed that the degrees of tumor differentiation, T stage, N stage, TNM stage, EC-LNI, EC-LNI number, and EC-LNI distance were significantly correlated with prognosis. A multivariate survival analysis showed that tumor differentiation, TNM stage, and EC-LNI were independent prognostic factors for OS, while TNM stage and EC-LNI were independent prognostic factors for DFS. The enrichment analysis identified the molecular targets and signaling pathways that can regulate cell proliferation, differentiation, and apoptosis. Extracapsular LNI has a high prognostic value in patients with esophageal cancer and is closely related to the stage of tumors. Our preliminary molecular mechanism research indicated that the molecular targets of EC-LNI are expected to become a new direction for the treatment of esophageal cancer.

Is HER2 ultra-low breast cancer different from HER2 null or HER2 low breast cancer? A study of 1363 patients.

This study aims to analyze whether there are any differences in clinicopathological features and prognosis between HER2 ultra-low, HER2-null, and HER2-low expression in Chinese breast cancer (BC) patients. The clinicopathological data of 1363 HER2-negative BC patients were retrospectively collected (from January 2018 to December 2019). HER2 status was further classified into HER2-null, HER2 ultra-low, and HER2-low. HER2-null expression is defined as infiltrating cancer cells completely free of staining. HER2 ultra-low expression is defined as ≤10% of infiltrating cancer cells showing incomplete and faint/weak membrane staining. HER2-low expression is defined as HER2 immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization (ISH) assay. Of 1363 patients, there were 86 (6.3%) HER2-null patients, 395 (29.0%) HER2 ultra-low patients, and 882 (64.7%) HER2-low patients. HER2 ultra-low patients were different from HER2-low patients in terms of N stage, hormone receptor (HR) status, Ki-67 expression, and type of surgery. There were also significant differences in histologic type and postoperative endocrine therapy between HER2 ultra-low and HER2-null patients. HR+ (81.0%) tumors was more common than HR- (19.0%) in HER2 ultra-low patients. In addition, there was a significant difference in HR status between HER2 ultra-low and HER2-low patients (P = 0.001). The survival analysis showed that HER2 status had no effect on disease-free survival (DFS) in HER2-negative patients (all P>0.05). However, regardless of HER2 status, HR+ patients had better DFS than HR- patients (P = 0.003). Cox multivariate analysis revealed that age (HR [95% CI] = 0.950 [0.928, 0.972], P < 0.001), HR status (HR [95% CI] = 3.342 [1.658, 6.736], P = 0.001), and postoperative endocrine therapy (HR [95% CI] = 0.048 [0.048, 0.023], P < 0.001) were important influencing factors of DFS in HER2-negative BC patients. HER2 ultra-low BC patients demonstrated distinct clinicopathological features from HER2-null and HER2-low tumors; while, HER2 status (null, ultra-low, or low) had no prognostic value in these HER2-negative BC population. Consistent with the published literature, HR status was an independent prognostic factor for DFS in HER2-negative BC patients.

The crucial value of serum ferritin in assessing high-risk factors and prognosis for patients with endometrial carcinoma

BackgroundEndometrial carcinoma is a common malignant tumor in female reproductive system. At present, there is no effective and economic prognostic index. This study aimed to investigate the effect of serum ferritin levels on the prognosis of endometrial carcinoma.MethodsData of 367 patients who diagnosed with endometrial carcinoma at the First Affiliated Hospital of Chongqing Medical University between January 2012 and August 2018 was retrospectively analyzed. The prediction accuracy was evaluated by receiver operating characteristics curves and Youden's J statistics. Hosmer–lemeshow test was used to confirm the goodness of fit of the model. The prognostic value of serum ferritin on disease free survival (DFS) and overall survival (OS) of endometrial carcinoma was evaluated by univariate log-rank tests and multivariate cox regression models.ResultsPreoperative high serum ferritin was correlated with older age, high grade, specific histological subtypes and recurrence of endometrial carcinoma (P < 0.05). The DFS and OS of 198 patients with elevated serum ferritin levels were significantly lower than those with low serum ferritin levels (P = 0.001 and P = 0.002, respectively). In multivariate analysis, serum ferritin was an independent prognostic factor for DFS and OS in endometrial carcinoma (P = 0.012, P = 0.028).ConclusionThrough our research, we found that the high expression of serum ferritin level was not only related to low DFS and OS in patients with endometrial carcinoma, but also related to the high-risk factors of endometrial carcinoma recurrence. So serum ferritin levels may be used to predict the poor prognosis of patients with endometrial carcinoma.

Combining perineural invasion with staging improve the prognostic accuracy in colorectal cancer: a retrospective cohort study

BackgroundCurrent guidelines only propose the importance of perineural invasion(PNI) on prognosis in stage II colon cancer. However, the prognostic value of PNI in other stages of colorectal cancer (CRC) is ambiguous.MethodsThis single-center retrospective cohort study included 3485 CRC patients who underwent primary colorectal resection between January 2013 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University. Associations of PNI with overall survival (OS) and disease-free survival (DFS) were evaluated using multivariable Cox proportional hazards regression models. In addition, interaction analyses were performed to explore the prognostic effects of PNI in different clinical subgroups.ResultsAfter median follow-up of 61.9 months, we found PNI was associated with poorer OS (adjusted hazard ratio [aHR], 1.290; 95% CI, 1.087–1.531) and DFS (aHR, 1.397; 95% CI, 1.207–1.617), irrespective of tumor stage. Interestingly, the weight of PNI was found second only to incomplete resection in the nomogram for risk factors of OS and DFS in stage II CRC patients. Moreover, OS and DFS were insignificantly different between stage II patients with PNI and stage III patients (both P > 0.05). PNI was found to be an independent prognostic factor of DFS in stage III CRC (aHR: 1.514; 95% CI, 1.211–1.892) as well. Finally, the adverse effect of PNI on OS was more significant in female, early-onset, and diabetes-negative patients than in their counterparts (interaction P = 0.0213, 0.0280, and 0.0186, respectively).ConclusionPNI was an important prognostic factor in CRC, more than in stage II. The survival of patients with stage II combined with perineural invasion is similar with those with stage III. PNI in stage III CRC also suggests a worse survival.

Clinicopathological characteristics and prognosis of triple-negative breast cancer invasive ductal carcinoma with ductal carcinoma in situ.

The purpose of this study is to compare and analyze the clinicopathological characteristics and prognosis of patients with invasive ductal carcinoma coexisting with ductal carcinoma in situ (IDC-DCIS) and invasive ductal carcinoma (IDC) in triple-negative breast cancer (TNBC), and to explore the factors affecting the prognosis, so as to provide new ideas for clinical diagnosis and treatment of these patients. The patients with TNBC underwent surgery in the Department of Breast Surgery of Harbin Medical University Cancer Hospital from October 2012 to December 2018 were retrospectively analyzed and divided into IDC-DCIS group and IDC group. The clinicopathological characteristics and prognosis of the two groups were compared. P < 0.05 was considered statistically significant. A total of 358 patients were enrolled. There were significant differences in age (P = 0.002), family history (P = 0.016), menopausal status (P = 0.003), KI-67% (P < 0.001), lymphovascular invasion (P = 0.010), histologic grade of IDC (P < 0.001) and multifocal (P < 0.001) between the two groups. The disease-free survival (DFS) of the IDC-DCIS group was better than that of the IDC group (the 5-year DFS was 87.9% vs. 82.6%, P = 0.045), but the overall survival (OS) of the two groups was not statistically significant (the 5-year OS was 96.2% vs. 96.0%, P = 0.573). In addition, the coexistence of DCIS (P = 0.030), lymph node pathologic stage (P = 0.001), tumor location (P = 0.011), and adjuvant chemotherapy (P < 0.001) were independent prognostic factors for DFS. In TNBC, the IDC-DCIS group had less invasive biological characteristics. The DFS of the IDC-DCIS group was better than that of the IDC group, but there was no statistical difference in OS between the two groups. In addition, the coexistence of DCIS, lymph node stage, tumor location and adjuvant chemotherapy may be independent prognostic factors for DFS.

Mutational spectrum for guiding the decision of adjuvant treatment in patients with resected biliary tract carcinoma.

Systemic chemotherapy or chemoradiation therapy has proven to be effective in treating advanced biliary tract carcinoma (BTC). However, its efficacy in the adjuvant setting remains controversial. Therefore, this study aimed to determine the prognostic significance of genomic biomarkers in resected BTC and their potential role in stratifying patients for adjuvant treatment. We retrospectively reviewed 113 BTC patients who underwent curative-intent surgery and had available tumor sequencing data. Disease-free survival (DFS) was the primary outcome examined and univariate analysis was used to identify gene mutations with prognostic value. Favorable and unfavoratble gene subsets were distinguished from the selected genes through grouping, respectively. Multivariate Cox regression was used to identify independent prognostic factors of DFS. Our results indicated that mutations in ACVR1B, AR, CTNNB1, ERBB3, and LRP2 were favorable mutations, while mutations in ARID1A, CDKN2A, FGFR2, NF1, NF2, PBRM1, PIK3CA, and TGFBR1 were unfavorable mutations. In addition to age, sex, and node positive, favorable genes (HR = 0.15, 95% CI = 0.04-0.48, p = 0.001) and unfavorable genes (HR = 2.86, 95% CI = 1.51-5.29, p = 0.001) were identified as independent prognostic factors for DFS. Out of the 113 patients, only 35 received adjuvant treatment whereas the majority (78) did not. For patients with both favorable and unfavorable mutations undetected, adjuvant treatment showed negative effect on DFS (median DFS: S441 vs. 956 days, p = 0.010), but there was no significant difference in DFS among those in other mutational subgroups. Genomic testing might be useful in guiding the decisions regarding adjuvant treatment in BTC.

The relationship between the change with neoadjuvant chemotherapy in the tumor-infiltrating lymphocyte (TIL) expressions and pathological response in breast cancer patients.

3114 Background: Many prognostic biomarkers for survival have been studied in the neoadjuvant setting for locally advanced breast cancer (LABC). Our study assessed the correlation between the change in tumour-infiltrating lymphocytes (TIL) before and after neoadjuvant chemotherapy (NAC) in breast tissue and its impact on survival in patients with LABC. Methods: Eighty-four LACB patients were retrospectively analysed in this study. TIL was assessed by means of immunohystochemistry (Eclipse Ni, Nikon, Japan) in paraffin-embedded blocks obtained by core-needle biopsy or surgical specimen with respect to the 'TIL working group' criteria. Results: TIL scores were grouped as 0%, &lt;10%, 10-50%, and &gt;50%, the median TIL percentage was 17.5% before NAC and 5% after NAC, and the difference was statistically significant (p&lt;0.001). Postop-Ki-67 (p=0.005), molecular subtype (p=0.027), pre-NAC TIL score (p=0.006), post-NAC TIL score (p&lt;0.001), postop-Ki-67 (p=0.005) and preoperative residual cancer burden tumour-infiltrating lymphocyte (RCB-TIL) (p&lt;0.001) were significantly correlated with pCR. Higher TIL scores were significantly associated with higher PCR rates. Univariate analysis for disease-free survival (DFS) and overall survival (OS) revealed that postop-Ki-67 level and presence of pCR and postoperative ki-67 score (p=0.031) were significant prognostic factors, respectively. The independent prognostic factor for DFS were postop-Ki-67 score (p=0.012, RR: 6.16, 95% CI: 1.48-9.12), post-NAC TIL score (p=0.041, RR: 0.42, 95% CI: 0.16-1.06) and the presence of pCR (p=0.038, RR: 0.10, 95% CI: 0.01-0.87). Logistic regression analysis showed that a preoperative ki-67 score greater than 14% (p=0.001, OR: 4.55; 95% CI: 0.11-1.49), a postoperative ki-67 score equal to or lower than 14% (p=0.011, OR: 1.10; 95% CI: 0.42-2.29), preop-grade 3 (p=0.01, OR: 2.65; 95% CI: 0.85-3.14), low postop-TIL score (p&lt;0.001, OR: 3.14; 95% CI: 0.79-4.11) were significant predictive factors for pCR. Conclusions: Our study confirms the hypothesis that TIL expressions may be therapeutic targets, especially in specific molecular breast cancer subtypes.