Lower 5-year Disease-free Survival Research Articles

Preoperative Vertebral Fracture: A Prognostic Factor in Stage I-III Colorectal Cancer.

This study evaluated the prognostic impact of vertebral fractures (VFs) on the survival of patients with colorectal cancer (CRC). We included 299 patients with stage I-III CRC who had undergone elective surgery. The patients were divided into the VF group (n=94) and non-VF group (n=205). VFs were assessed using sagittal computed tomography image reconstruction (Th11-L5) performed preoperatively. Disease-free survival (DFS) and overall survival (OS) rates were analyzed. The VF group had lower 5-year DFS and OS rates compared to the non-VF group (both, p<0.001). The independent predictors of DFS were carbohydrate antigen 19-9 (CA19-9) ≥37.0 ng/ml, T3/T4 disease, stage III CRC, osteopenia, and VF; for OS, CA19-9 ≥37.0 ng/ml, stage III, osteopenia, and VF. VF, compared with osteopenia, was a more significant prognostic factor for DFS and OS in patients with stage I+ II CRC (both, p<0.001). Preoperative VF was associated with worse DFS and OS following CRC resection.

Prognostic significance of the neutrophil to lymphocyte ratio in locally advanced breast cancer.

The present study aimed to clarify the prognostic role of the pre-treatment neutrophil-to-lymphocyte ratio (NLR) for the response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC). Due to conflicting results in currently available data, the specific focus of the present study was on evaluating the associations between the pre-treatment NLR and the rate of achieving a pathological complete response (pCR) and survival outcomes. For the present study, data from a cohort of 465 consecutive patients with LABC who underwent NAC at King Feisal Specialist Hospital and Research Center (Riyadh, Saudi Arabia) between 2005 and 2014 were obtained from a prospective BC database and analyzed. Patients were stratified into two groups based on an optimal NLR cut-off determined using the receiver operating characteristic curve. Logistic regression analyses were conducted to assess variables associated with pCR, and Cox regression analyses were used to assess variables associated with survival outcomes. The low pre-treatment NLR group (≤2.2) was found to exhibit a higher likelihood of achieving a pCR (odds ratio, 2.59; 95% CI, 1.52-4.38; P<0.001), along with higher 5-year disease-free survival (DFS) [75.8 vs. 64.9%; hazard ratio (HR), 0.69; 95% CI, 0.50-0.94; P=0.02] and 5-year overall survival (OS; 90.3 vs. 81.9; HR, 0.62; 95% CI, 0.39-0.98; P=0.04) rates compared with those in the high NLR group (>2.2). Sub-group analysis revealed that the observed significance in survival outcomes was driven by the triple-negative BC (TNBC) subgroup. Patients with residual TNBC disease and a high pre-treatment NLR were observed to have lower 5-year DFS (44.4 vs. 75.0%; P=0.02) and 5-year OS (55.9 vs. 84.5%; P=0.055) rates compared with those with residual TNBC disease and a low NLR. To conclude, data from the present study suggest that the pre-treatment NLR can serve as a viable independent prognostic factor for pCR following NAC in patients with LABC and for survival outcomes, particularly for patients with TNBC.

Preoperative neutrophil/lymphocyte ratio as prognostic factor in epithelial ovarian cancer

To determine if there is an association between the neutrophil to lymphocyte ratio (NLR) and prognosis in patients with epithelial ovarian cancer (EOC) diagnosed and treated in a Spanish population. Retrospective cohort of patients with epithelial ovarian cancer who had neutrophil and lymphocyte values in complete blood count before the histopathological diagnosis and survival of at least three months, in an intermediate complexity hospital. Convenience sampling. Measured variables included age, menopausal stage, parity, International Federation of Gynecology and Obstetrics (FIGO) stage, treatment type, residual tumor, lymph node involvement, presence of ascites, cytology, histologic type, differentiation grade, and CA-125 values. Additionally, outcomes, overall survival, disease/progression-free survival were also measured. Bivariate inferential and Cox regression analyses were performed. Out of 78 candidates, 60 women with EOC were included. Of them, 24 (40%) had a low NLR (≤ 2,9) while 36 (60%) had a high NLR (> 2,9). An association was found between high NLR levels and suboptimal cytoreductive surgery. High NLR ratios were associated with lower overall survival (Hazard ratio (HR): 4.1; 95% CI: 1.4-11.8) and lower 5-year disease-free survival (HR: 2.6; 95% CI: 1.2-5.7). A plasma neutrophil to lymphocyte ratio of more than 2.9 was associated with poor prognosis in patients with epithelial ovarian cancer in our setting. There is a need to establish the optimal cut-off point and conduct prospective studies with larger patient numbers in order to support this information.

The Clinical Behavior and Recurrence Patterns of Oral Cavity Cancer in Oral Lichen Planus Patients.

Oral lichen planus (OLP) is a chronic inflammatory disorder involving epithelia with squamous differentiation. Although described as a potential malignant precursor, the characteristics of malignancies arising among these patients are not widely described. Our goal was to describe the patterns of disease recurrence of patients with oral cavity squamous cell carcinoma (OSCC) arising on the background of OLP. A retrospective analysis of all surgically treated patients with OSCC at a university-affiliated tertiary care center between 2000 and 2020. Two hundred seventy-nine patients with OSCC treated surgically were included. Forty (14.3%) had OLP. The mean age of patients with OLP was 70.9 years compared with 64.3 years for non-OLP patients (p = 0.03). OLP patients had a significantly higher rate of disease recurrence, persistence, or multiple primary disease (70% vs. 33.9%, p < 0.001). The mean number of sequential oncologic events for each patient with recurrence was also significantly higher among OLP patients (1.86 vs. 1.36, p = 0.03), a difference explained by a higher rate of multiple primary presentations (0.71 vs. 0.28, p = 0.008). A significant difference in disease-free survival (DFS) was demonstrated between the groups as patients with OLP had a lower 5-year DFS (34.7% vs. 61.3%, log-rank p value <0.001). On multivariate analysis, OLP was significantly associated with multiple primary events (p < 0.001, Odds ratio = 7.42, 95% confidence interval 2.9-19). OSCC patients with OLP background demand close clinical follow-up, as multiple primary disease is significantly more common and the DFS is significantly lower among these patients. A thorough clinical evaluation for all oral cavity subsites is mandatory. 3 Laryngoscope, 134:3146-3151, 2024.

Preoperative tracheostomy is associated with thyroid gland invasion and poorer prognosis in laryngectomized patients.

Patients with laryngeal cancer may necessitate tracheostomy placement to alleviate compromised airways. However, the impact of tracheostomy on thyroid gland invasion and its implications for prognosis in individuals who further undergo total laryngectomy remains unclear. This study aimed to assess thyroid gland invasion rates and explore the 5-years disease-free and overall survival in laryngectomized patients stratified by preoperative tracheostomy. All patients who underwent total laryngectomy for laryngeal cancer between 2003 and 2023 at a tertiary referral center were retrospectively reviewed. Logistic univariable and multivariable regressions were performed to identify factors associated with thyroid gland invasion. Survival analyses were performed using the Kaplan-Meier estimator. A total of 119 laryngectomized patients were included (mean age: 63 ± 10 years, range 35-89, 110 [92.4%] males); 27 (22.7%) underwent preoperative tracheostomy. In 16 (13.4%) patients, tumor cells were found within the thyroid gland. In a multivariable analysis, thyroid gland invasion was independently associated with preoperative tracheostomy (odds ratio [OR] 3.13, 95% confidence interval [CI] 2.45-6.19), pN2 + (OR 2.13, 95% CI 1.8-5.14), positive margins (OR 1.36, 95% CI 1.01-1.77), lower 5-year disease-free survival (38% vs. 57%, p = 0.01), and lower 5-year overall survival (40% vs. 56%, p = 0.03). Preoperative tracheostomy is an independent predictive factor for thyroid gland invasion and has adverse oncological outcomes in laryngectomized patients. Conversely, the rates of thyroid gland invasion are low when tracheostomy was not performed beforehand.

Nodular type predominance of head and neck cutaneous malignant melanoma in Asian populations leads to poor outcome and low survival.

Cutaneous malignant melanomas of the head and neck (HNM) are proposed to have notable histological and clinical differences from those at other sites (other melanoma); however, HNMs among Asians have remained poorly understood. This study aimed to investigate the clinicopathological features and prognostic factors of HNM in Asians. Asian melanoma patients who underwent surgical treatment from January 2003 to December 2020 were retrospectively reviewed. The clinicopathological features and risk factors for local recurrence, lymph node metastasis, and distant metastasis were analyzed. Among 230 patients, 28 (12.2%) were diagnosed with HNM, and 202 (87.8%) with other melanoma. The histologic subtype significantly differed as the nodular type was predominant in HNM whereas the acral lentiginous type was predominant in other melanoma ( P < 0.001). HNM was significantly associated with higher local recurrence ( P = 0.045), lymph node metastasis ( P = 0.048), distant metastasis ( P = 0.023), and lower 5-year disease-free survival ( P = 0.022) than other melanoma. Ulceration was the risk factor for lymph node metastasis based on multivariable analysis ( P = 0.013). A high proportion of HNM present as the nodular subtype in Asians, leading to poor outcomes and low survival. Therefore, more cautious surveillance, evaluation, and aggressive treatment are required.

A novel tool to predict nodal metastasis in small pancreatic neuroendocrine tumors: A multicenter study

BackgroundNonfunctional pancreatic neuroendocrine tumors display a wide range of biological behavior, and nodal disease is associated with metastatic disease and poorer survival. The aim of this study was to develop a tool to predict nodal disease in patients with small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors. MethodsA multicenter retrospective study was performed on patients undergoing resection for small nonfunctional pancreatic neuroendocrine tumors. Patients with genetic syndromes, metastatic disease at diagnosis, neoadjuvant therapy, or positive resection margin were excluded. Factors associated with nodal disease were identified to develop a predictive model. Internal validation was performed using bootstrap with 1,000 resamples. ResultsNodal disease was observed in 39 (11.1%) of the 353 patients included. Presence of nodal disease was significantly associated with lower 5-year disease-free survival (71.6% vs 96.2%, P < .001). Two predictors were strongly associated with nodal disease: G2 grade (odds ratio: 3.51, 95% confidence interval: 1.71–7.22, P = .001) and tumor size (per mm increase, odds ratio: 1.14, 95% confidence interval: 1.03–1.25, P = .009). Adequate discrimination was observed with an area under the curve of 0.71 (95% confidence interval: 0.63–0.80). Based on risk distribution, 3 risk groups of nodal disease were identified; low (<5%), intermediate (≥5% to <20%), and high (≥20%) risk. The observed mean risk of nodal disease was 3.7% in the low-risk patients, 9.6% in the intermediate-risk patients, and 30.4% in the high-risk patients (P < .001). The 10-year disease-free survival in the low, intermediate, and high-risk groups was 100%, 88.8%, and 50.1%, respectively. ConclusionOur model using tumor grade and size can predict nodal disease in small nonfunctional pancreatic neuroendocrine tumors. Integration of this tool into clinical practice could help guide management of these patients.

Predictive modelling for high-risk stage II colon cancer using auto-artificial intelligence.

Recently, stratification of high-risk stage II colon cancer (CC) and the need for adjuvant chemotherapy have been the focus of attention. The aim of this retrospective study was to define high-risk factors for recurrent stage II CC using Prediction One auto-artificial intelligence (AI) software and develop a new predictive model for high-risk stage II CC. The study included 259 consecutive pathological stage II CC patients undergoing curative resection at our institution between January 2000 and December 2016. Prediction One software with five-fold cross-validation was used to create a predictive model and receiver operating characteristic (ROC) curve. Predictive accuracy of AI was evaluated using the area under the ROC curve (AUC). We also evaluated the importance of variables (IOV) using a method based on permutation feature importance (IOV > 0.01 defined high-risk factors) to evaluate disease-free survival (DFS). The median observation period was 6.1 (range = 0.3-15.8) years. Thirty-seven patients had recurrence (14.3%); the AUC of the AI model was 0.775. Preoperative carcinoembryonic antigen > 5.0ng/mL (IOV = 0.047), venous invasion (IOV = 0.014), and obstruction (IOV = 0.012) were high-risk factors contributing to cancer recurrence. Patients with 2-3 high-risk factors had lower 5-year DFS than those with 0-1 factor (87.4% vs 62.7%, p < 0.001). We developed a new predictive model that could predict recurrent high-risk stage II CC with high probability using auto-AI Prediction One software. Patients with ≥ 2 of the aforementioned factors are considered to have high risks for recurrent stage II CC and may benefit from adjuvant chemotherapy.

Comparison of the Oncological Outcomes Between Robot-Assisted and Abdominal Radical Hysterectomy for Cervical Cancer Based on the New FIGO 2018 Staging System: A Multicentre Retrospective Study.

ObjectiveTo compare the 3-year oncological outcomes of robot-assisted radical hysterectomy (RRH) and abdominal radical hysterectomy (ARH) for cervical cancer.MethodsBased on the clinical diagnosis and treatment for cervical cancer in the China database, patients with FIGO 2018 stage IA with lymphovascular space invasion (LVSI)-IB2 cervical cancer disease who underwent RRH and ARH from 2004 to 2018 were included. Kaplan–Meier survival analysis was used to compare the 3-year overall survival (OS) and disease-free survival (DFS) rate between patients receiving RRH and those receiving ARH. The Cox proportional hazards model and propensity score matching were used to estimate the surgical approach-specific survival.ResultsA total of 1,137 patients with cervical cancer were enrolled in this study, including the RRH group (n = 468) and the ARH group (n = 669). The median follow-up time was 45 months (RRH group vs. ARH group: 24 vs. 60 months). Among the overall study population, there was no significant difference in 3-year OS and DFS between the RRH group and the ARH group (OS: 95.8% vs. 97.6% p = 0.244). The Cox proportional hazards analysis showed that RRH was not an independent risk factor for 3-year OS (HR: 1.394, 95% CI: 0.552–3.523, p = 0.482). However, RRH was an independent risk factor for 3-year DFS (HR: 1.985, 95% CI: 1.078–3.655 p = 0.028). After 1:1 propensity score matching, there was no significant difference in 3-year OS between the RRH group and the ARH group (96.6% vs. 98.0%, p = 0.470); however, the 3-year DFS of the RRH group was lower than that of the ARH group (91.0% vs. 96.1%, p = 0.025). The Cox proportional hazards analysis revealed that RRH was not an independent risk factor for 3-year OS (HR: 1.622, 95% CI: 0.449–5.860 p = 0.461), but RRH was an independent risk factor for 3-year DFS (HR: 2.498, 95% CI: 1.123–5.557 p = 0.025).ConclusionAmong patients with stage I A1 (LVSI +)-I B2 cervical cancer based on the FIGO 2018 staging system, RRH has a lower 3-year DFS than ARH, suggesting that RRH may not be suitable for early cervical cancer patients.

PB2135: BURKITT LYMPHOMA INTERNATIONAL PROGNOSTIC INDEX (BL-IPI): IS IT EFFICIENT ENOUGH IN ADULT BURKITT LYMPHOMA PATIENTS?

Background: Burkitt lymphoma is a rare but clinically severe subtype of non-Hodgkin lymphoma. An ideal risk scoring system specific to Burkitt lymphoma had not been available for many years, however Burkitt Lymphoma International Prognostic Index (BL-IPI) has been recently proposed by Olszewski et al. BL-IPI is consisted of following risk factors; age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase (LDH) ≥ 3X upper limit of normal (ULN), and central nervous system (CNS) involvement. Accordingly, patients are grouped as low risk (zero risk factor) disease, intermediate risk (one risk factor) and high risk (≥2 risk factors). Aims: Our aims were to examine the basic characteristics and survival rates of Burkitt lymphoma patients that are being treated in our institution, to determine the prognostic factors which affect survival and to evaluate the efficacy of BL-IPI and other risk scoring systems in our patient population. Methods: Patients who were 18 years or older and diagnosed with Burkitt lymphoma between 2000-2021 at Hacettepe University Hospital were included in our study. Patient, disease and treatment characteristics were reviewed through hospital electronic health records. Disease free survival (DFS) and overall survival (OS) were determined as the primary endpoints. Variables that have prognostic impact were identified through univariate and multivariate analyses. Finally, the efficacy of BL-IPI was tested in our patient population. Statistical analyses were conducted using SPSS version 25. Results: A total of 71 patients whose median age of diagnosis was 40 (IQR: 29-55) and median follow-up time was 11,4 months (minimum 0,33, maximum 243,67 months) were included in our study. 1 year OS was estimated as 58%, 3 year OS as 53% and 3 year DFS as 64%. Factors affecting survival were examined and in univariate analyses; performance status ≥ 2, stage 4 disease, bone marrow involvement, CNS involvement, serum LDH > ULN, hypoalbuminemia, anemia and thrombocytopenia were associated with lower 3-year OS (p<0,05); while stage 4 disease, bone marrow involvement, anemia and thrombocytopenia were associated with lower 3-year DFS (p<0,05). In multivariate analysis, only performance status ≥ 2, stage 4 disease, bone marrow involvement and thrombocytopenia caused a statististically significant increase in death rate (p<0,05). CNS involvement caused a near significant increase (p=0,067). 25,4% of the patients had low risk, 31% of the patients had intermediate risk and 34,6% of the patients had high risk disease according to BL-IPI. 3-year OS rates were 82%, 65% and 27% respectively, and 3-year PFS rates were 81%, 71% and 36% respectively. Image:Summary/Conclusion: Our study supports the fact that BL-IPI predicts survival efficiently, however taking our aforementioned results into consideration, we propose that instead of “CNS involvement”, “CNS involvement and bone marrow involvement” or “stage 4 disease” could be added to the score as a risk factor. In the study conducted by Olszewski et al., 58% of the patients in the low risk group had advanced stage disease, however only 12% had bone marrow involvement, which is a relatively low ratio compared to literature. Studies involving larger cohorts who have higher bone marrow involvement ratios consistent with the literature are undoubtedly needed to support this proposition.

Using a 31-Gene Expression Profile Test to Stratify Patients with Stage I-II Cutaneous Melanoma According to Recurrence Risk: Update to a Prospective, Multicenter Study.

Simple SummaryMany people with skin cancer will have their cancer come back. The 31-gene expression profile (31-GEP) test can help predict if a cancer has a low (Class 1) or high (Class 2) chance of returning. This study looked at 86 patients with early skin cancer to see how well the 31-GEP test predicted if their cancer would return. None of the patients with a Class 1 GEP result had their cancer return within 3 years, but one-fourth of patients with a Class 2 result did. This study showed that the 31-GEP test can help predict if a patient’s skin cancer will return. Accurate risk prediction can help doctors make better treatment plans for patients with skin cancer.Background: Fifteen to forty percent of patients with localized cutaneous melanoma (CM) (stages I–II) will experience disease relapse. The 31-gene expression profile (31-GEP) uses gene expression data from the primary tumor in conjunction with clinicopathologic features to refine patient prognosis. The study’s objective was to evaluate 31-GEP risk stratification for disease-free survival (DFS) in a previously published cohort with longer follow-up. Methods: Patients with stage IB–II CM (n = 86) were prospectively tested with the 31-GEP. Follow-up time increased from 2.2 to 3.9 years. Patient outcomes were compared using Kaplan-Meier and Cox regression analysis. Results: A Class 2B result was a significant predictor of 3-year DFS (hazard ratio (HR) 8.4, p = 0.008) in univariate analysis. The 31-GEP significantly stratified patients by risk of relapse (p = 0.005). A Class 2B result was associated with a lower 3-year DFS (75.0%) than a Class 1A result (100%). The 31-GEP had a high sensitivity (77.8%) and negative predictive value (95.0%). Conclusions: The 31-GEP is a significant predictor of disease relapse in patients with stage IB–II melanoma and accurately stratified patients by risk of relapse.

Potential evidence of peritoneal recurrence in Stage-II colon cancer from the control arm of CALGB9581

BackgroundRelapse of early-stage colon cancer (CC) after curative-intent resection occurs. We hypothesized that known risk factors for peritoneal metastases (PM) can define a high-risk state (HRS) that predicts recurrence and mortality. MethodsCALGB9581 trial patients receiving no adjuvant treatment after stage-II CC resection were included. Positive radial margins, T4 invasion, obstruction/perforation or lymphovascular invasion defined the HRS. Cox proportional hazard models determined association with overall (OS) and disease-free survival (DFS). ResultsMedian follow-up in 873 included patients was 8.1 years. Five-year OS was 85.8%. HRS+ patients had lower 5-year DFS (68.7 vs. 82.4%, P = 0.003) and OS (75.5 vs. 87.8%, P = 0.001). HRS+ was independently predictive of worse DFS and OS (HR 1.52 and 1.64, P < 0.01). Among recurrences, HRS+ patients showed shorter median OS (3.3 vs. 5.3 years, P = 0.01). ConclusionsHRS criteria identify a cohort of CC patients at high-risk of recurrence and death. Studies of novel surveillance techniques in such patients are warranted.

Prevalence of nodal involvement in rectal cancer after chemoradiotherapy.

The purpose of this study was to investigate the prevalence of ypN+ status according to ypT category in patients with locally advanced rectal cancer treated with chemoradiotherapy and total mesorectal excision, and to assess the impact of ypN+ on disease recurrence and survival by pooled analysis of individual-patient data. Individual-patient data from 10 studies of chemoradiotherapy for rectal cancer were included. Pooled rates of ypN+ disease were calculated with 95 per cent confidence interval for each ypT category. Kaplan-Meier and Cox regression analyses were undertaken to assess influence of ypN status on 5-year disease-free survival (DFS) and overall survival (OS). Data on 1898 patients were included in the study. Median follow-up was 50 (range 0-219) months. The pooled rate of ypN+ disease was 7 per cent for ypT0, 12 per cent for ypT1, 17 per cent for ypT2, 40 per cent for ypT3, and 46 per cent for ypT4 tumours. Patients with ypN+ disease had lower 5-year DFS and OS (46.2 and 63.4 per cent respectively) than patients with ypN0 tumours (74.5 and 83.2 per cent) (P < 0.001). Cox regression analyses showed ypN+ status to be an independent predictor of recurrence and death. Risk of nodal metastases (ypN+) after chemoradiotherapy increases with advancing ypT category and needs to be considered if an organ-preserving strategy is contemplated.

Association of expression and genotypes of thymidylate synthase in non-small cell lung cancer patients with different clinicopathological characteristics

Abstract Objective To explore the expression and genotypes of thymidylate synthase (TS) in patients of non-small cell lung cancer (NSCLC) with different clinicopathological characteristics. Methods The expression profiles of TS were examined by immunohistochemical staining and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in 160 patients with NSCLC. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect TS-5′UTR tandem repeats, G/C nucleotide polymorphisms, and 3′UTR 6 bp deletion/insertion polymorphisms. The relationships between clinicopathological characteristics and TS expression or genotypes were investigated through χ 2 test. Kaplan–Meier survival analysis was used to analyze the association between TS expression and overall survival (OS) and disease-free survival (DFS) of NSCLC patients. Results The expression levels of TS protein and TS gene in NSCLC tissues were significantly higher than that in paracancerous tissues (P &lt; 0.05). Furthermore, high expression of TS protein and 5′UTR polymorphism of TS gene showed significant correlation with differentiation, TNM stage, and lymph node metastases. The frequency of −6 bp/−6 bp genotypes in patients with NSCLC was 43.13% (69/160), which was higher than others. In addition, the rate of TS protein overexpression in NSCLC patients with 3R/3R was 79.79%, which was higher than others. Interestingly, high expression of TS protein predicted shorter DFS and OS and lower 3-year DFS rate and 3-year OS rate. Conclusions The expression levels of TS in NSCLC were significantly increased and may help to predict the prognosis of NSCLC, and high expression of TS protein and 5′UTR polymorphism of TS gene were significantly related to differentiation, TNM stage, and lymph node metastases.

Wilms\u2019 tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation

BackgroundSequential monitoring of Wilms’ tumor gene 1 (WT1) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict relapse in adult acute myeloid leukemia (AML). However, the prognostic role of WT1 in pediatric AML after allo-HSCT is unclear. Thus, we determined to see whether sequential monitoring of WT1 after allo-HSCT could predict relapse in AML children.MethodsPediatric AML patients receiving allo-HSCT from January 21, 2012 to December 20, 2018 at the Peking University Institute of Hematology were included in this study. WT1 expression level was determined by TaqMan-based reverse transcription-polymerase chain reaction. WT1 sequential monitoring was performed 1, 2, 3, 4.5, 6, 9, and 12 months post-transplantation and at 6-month intervals thereafter. The primary end point was relapse. The secondary end points included disease-free survival (DFS), overall survival (OS), and non-relapse mortality (NRM). Kaplan–Meier analysis was used for DFS and OS estimates, while competing risk analysis was used for estimating relapse and NRM.ResultsOf the 151 consecutive patients included, the median age was 10 years (range, 1–17). The optimal cutoff value of WT1 within 1 year after allo-HSCT to predict relapse was 0.8% (80 WT1 copies/104 ABL copies), with a sensitivity of 60% and specificity of 79%. Compared with WT1 expression < 0.8%, WT1 expression ≥0.8% indicated significantly higher 5-year cumulative incidence of relapse (CIR, 35.1% vs. 11.3%; P = 0.001), lower 5-year disease-free survival (DFS, 60.4% vs. 80.8%; P = 0.009), and lower 5-year overall survival (OS, 64.9% vs. 81.6%; P = 0.038) rates. Multivariate analyses showed that WT1 was an independent risk factor for relapse (HR 2.89; 95% confidence interval (CI), 1.25–6.71; P = 0.014). Both the CIR (5-year CIR: 8.3% vs. 11.3%; P = 0.513) and DFS (5-year DFS: 91.7% vs. 80.8%; P = 0.208) were comparable between patients achieving minimal residual disease (MRD) negativity after preemptive interferon-α (IFN-α) treatment and those without MRD after allo-HSCT, which were better than those of MRD-positive patients without preemptive therapies.ConclusionsSequential monitoring of WT1 could predict relapse in pediatric AML after allo-HSCT. WT1-directed immunotherapy may have the potential to prevent relapse and improve survival.

Lymph-Vascular Space Invasion in Patients with Stages IA2-IIA2 Cervical Cancer Treated with Laparoscopic versus Open Radical Hysterectomy.

ObjectiveTo explore the relationship between laparoscopic radical hysterectomy (LRH) and cervical cancer lymph-vascular space invasion (LVSI) by comparing the prevalence of LVSI in cervical cancer patients who underwent LRH versus open radical hysterectomy (ORH).MethodsThe study participants were 1087 cervical cancer patients (FIGO 2009 stages IA2-IIA2) with pathologically confirmed with or without LVSI who underwent radical hysterectomy at Shengjing Hospital of China Medical University from 2013 through 2018. The patients were divided according to the type of surgical procedure into an LRH group (n=148) and an ORH group (n=939).ResultsIn the LRH group, 31.76% of patients (47/148) had LVSI-positive tumors compared to 33.23% of patients (312/939) in the ORH group; the difference was not significant (p=0.724). No between-group differences in LVSI prevalence according to lymph node metastasis, interstitial infiltration depth, differentiation degree, and parametrial infiltration were found. However, the number of LVSI-positive patients whose cervical cancer lesions >4 cm (stage I B2 and II A2) was significantly higher in the LRH group than in the ORH group (Odds Ratio [OR] 0.333, 95% confidence interval [CI] 0.157–0.706, p=0.005). The 3-Year disease-free survival (DFS) in the LRH group is lower than that in the ORH group (94.75% vs 97.27%), but there was no significance (P=0.187). Furthermore, the percentage of LVSI-positive tumors in patients with lymph node metastases was significantly higher than those without lymph node metastases (OR 2.897, 95% CI 2.129–3.942, p=0.000). The 3-Year DFS were 98.22% in the LVSI negative patients and 93.78% in the LVSI positive patients, the difference was significant (P=0.002).ConclusionA higher risk of lymph node metastasis and a lower 3-Year DFS was found in the LVSI-positive patients. In case of LVSI, it would be dangerous to treat patient in laparoscopy, especially in case of cervical cancer lesions >4cm.

Prognostic significance of the primary tumor site and immune indexes in patients with estrogen receptor-positive, human epidermal growth factor receptor-2-negative breast cancer.

The ability to predict high risk factors for recurrence after neoadjuvant chemotherapy (NAC) is controversial. The purpose of the present study was to investigate the prognostic significance of tumor location, tumor-infiltrating lymphocyte (TIL) level, and pretreatment lymphocyte-to-monocyte ratio (LMR) in determining the survival of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer after treatment with NAC. The clinical data of 285 ER-positive, HER2-negative patients with clinical stage II-III breast cancer were analyzed from January 2009 to January 2015. To explore the prognostic factors for ER-positive, HER2-negative patients, we combined the conventional clinicopathological prognostic factors with tumor location, pretreatment LMR, and TIL. In addition, samples from 79 patients, who did not achieve pathological complete response (pCR) testing after NAC, were selected for hematoxylin-eosin (HE) staining to analyze the effect of TIL on prognosis. An LMR >5.2 was correlated with better 5-year disease-free survival (DFS) and overall survival (OS; P<0.001 and P<0.001, respectively). Patients with lower-inner/central quadrant tumors had lower 5-year DFS and OS than patients with tumors in the other quadrants (P=0.012 and P=0.048). Patients with a lower TIL level (≤10%) had better 5-year DFS than patients with a higher TIL level (P=0.010). According to the results of the multivariate analyses, tumor location was an independent prognostic factor for 5-year DFS (P=0.021). Pretreatment LMR was associated with both 5-year DFS and OS (P<0.001 and P<0.001, respectively). In the subgroup analysis stratified by TIL level, the TIL level and the initial clinical stage were associated with 5-year DFS (P=0.027 and P<0.001, respectively). We explored the prognostic significance of the tumor site, TIL level, and pretreatment LMR level for ER-positive, HER2-negative patients. We concluded that the lower-inner/central quadrant tumors, TIL >10%, and pretreatment LMR level ≤5.2 were correlated with a poor prognosis. More aggressive NAC and/or endocrine therapy with internal mammary node radiotherapy (IMN-RT) should be administered to address the relatively poor prognosis of patients with breast carcinoma presenting the aforementioned adverse factors.

Long-term oncological outcomes of laparoscopic versus abdominal surgery in stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer patients with different tumor size: a big database in China

Objective: To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 （lymph-vascular space invasion-positive, LVSI+）- Ⅰb1 cervical cancer patients with different tumor sizes. Methods: Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results: (1) A total of 4 891 patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.367, 95%CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups （94.1% vs 95.4%, P=0.151）. While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS (HR=1.420, 95%CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS (P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups (P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.705, 95%CI: 1.088-2.674, P=0.020). Conclusions: For patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

Hazard Ratio Analysis of Laparoscopic Radical Hysterectomy for IA1 With LVSI-IIA2 Cervical Cancer: Identifying the Possible Contraindications of Laparoscopic Surgery for Cervical Cancer.

Objectives: This study aimed to compare the 5-year disease-free survival (DFS) and overall survival (OS) of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for IA1 with lymphovascular space invasion (LVSI)-IIA2 cervical cancer and to analyze the Cox proportional hazard ratio (HR) of LRH among the total study population and different subgroups.Methods: This was a multicenter retrospective cohort study. The oncological outcomes of LRH (n = 4,236) and ARH (n = 9,177) were compared. The HRs and 95% confidence intervals for the effect of LRH on 5-year OS and DFS were estimated by Cox proportional hazards models.Results: Overall, there was no difference in DFS between LRH and ARH in the unadjusted analysis (HR 1.11, 95% CI: 0.99–1.25, p = 0.075). The risk-adjusted analysis revealed that LRH was independently associated with inferior DFS (HR 1.25, 95% CI: 1.11–1.40, p < 0.001). There was no difference in OS between the two groups in the unadjusted analysis (HR 1.00, 95% CI: 0.85–1.17, p = 0.997) or risk-adjusted analysis (HR 1.15, 95% CI: 0.98–1.35, p = 0.091). For patients with FIGO stage IB1 and tumor size <2 cm, LRH was not associated with lower DFS or OS (p = 0.637 or p = 0.107, respectively) in risk-adjusted analysis. For patients with FIGO stage IB1 and tumor size ≥2 cm, LRH was associated with lower 5-year DFS (HR 1.42, 95% CI: 1.19–1.69, p < 0.001) in risk-adjusted analysis, but it was not associated with lower 5-year OS (p = 0.107). For patients with FIGO stage IIA1 and tumor size <2 cm, LRH was not associated with lower 5-year DFS or OS (p = 0.954 or p = 0.873, respectively) in risk-adjusted analysis. For patients with FIGO stage IIA1 and tumor size ≥2 cm, LRH was associated with lower DFS (HR 1.48, 95% CI: 1.16–1.90, p = 0.002) and 5-year OS (HR 1.69, 95% CI: 1.22–2.33, p = 0.002) in risk-adjusted analysis.Conclusion: The 5-year DFS of LRH was worse than that of ARH for FIGO stage IA1 with LVSI-IIA2. LRH is not an appropriate option for FIGO stage IB1 or IIA1 and tumor size ≥ 2 cm compared with ARH.

Prognostic effect of incongruous lymph node status in early-stage non-small cell lung cancer

IntroductionTumor recurrence is an important issue for patients with stage I non-small cell lung cancer (NSCLC) and adjuvant therapy is considered of no benefit to a tumor less than 4 cm. The purpose of this study was to evaluate the impact of positron emission tomography/computed tomography (PET/CT) on tumor recurrence in patients with a completely resected pN0 NSCLC less than 4 cm. MethodsBetween January 2011 and December 2016, 211 consecutive patients with diagnoses of stage I NSCLC less than 4 cm after complete resection were included. The maximum of standard uptake value (SUVmax) of primary tumor and the presence of positive lymph nodes on PET/CT scans were documented. Disease-free survival was evaluated by the Kaplan-Meier method and recurrence risk factors were identified by univariable and multivariable analyses. ResultsPatients with positive lymph nodes on PET/CT had a lower 5-year disease-free survival (37.6% vs 72.7%, p < 0.001). Multivariable analysis demonstrated that the tumor SUVmax >2.93, the presence of positive lymph nodes on PET/CT, and poor differentiation were significant factors for tumor recurrence. Patients with the tumor SUVmax >2.93 and positive lymph nodes on PET/CT simultaneously had 5.33-fold increase in the risk of recurrence (p < 0.001). ConclusionThe presence of positive lymph nodes on PET/CT scans can be a good indicator in predicting patients with high risk of developing recurrence in pN0 NSCLC less than 4 cm. This result helps identify patients likely to benefit from adjuvant therapy.