Poor 5-year Disease-free Survival Research Articles

A systematic review and meta-analysis of neoadjuvant imatinib use in locally advanced and metastatic gastrointestinal stromal tumors.

Several doubts remain regarding the optimal use of neoadjuvant imatinib in gastrointestinal stromal tumors (GISTs), such as ideal treatment duration, patient selection, and long-term survival outcomes. This manuscript provides a comprehensive review on neoadjuvant imatinib treatment outcomes and facilitate evidence-based decision-making for the use of imatinib therapy in GISTs. Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to September 9, 2023. Meta-analyses of proportions were performed for the outcomes of R0 resection, disease responses, and 1-year, 3-year, and 5-year overall survival (OS) as well as 1-year, 3-year, and 5-year disease free survival (DFS). Sensitivity analyses in the form of leave-one-out analyses, meta-regression, and subgroup analyses were performed for outcomes with substantial statistical heterogeneity. The search yielded 1254 articles, and 36 studies were included in our analysis. Meta-analysis of proportions revealed that 1-year, 3-year, and 5-year OS was 100%, 94%, and 88%, while 1-year, 3-year and 5-year DFS was 99%, 89%, and 79%, respectively. An R0 resection rate of 89% and a disease response rate of 67% was achieved after a mean duration of treatment of 8.41±0.367months. KIT exon 9 mutation was significantly associated with poorer 5-year DFS. This study quantified key outcomes for neoadjuvant imatinib in locally advanced and metastatic or recurrent GIST. Patients with gastric and rectal tumous stand to benefit from neoadjuvant imatinib with an optimal treatment duration of 8months. Furthermore, the potential utility of mutational analysis in guiding treatment with neoadjuvant imatinib was demonstrated.

Spatial immunophenotypes orchestrate prognosis in triple-negative breast cancer with Miller-Payne grade 4 following neoadjuvant chemotherapy

Some triple-negative breast cancer (TNBC) patients evaluated as Miller-Payne 4 with ypN0 after neoadjuvant chemotherapy (NACT) who have better prognoses should avoid escalation of therapy. We aim to identify these patients by evaluating pretherapeutic spatial distributions of immunophenotypes. Our retrospective study in patients with TNBC assessed as Miller-Payne grade 4/5 with ypN0 showed that Miller-Payne 4 with ypN0 group had poorer 5-year disease-free survival (DFS, 63.8% vs. 83.0%, p = 0.003) and the 5-year overall survival (OS, 71.0% vs. 85.5%, p = 0.007) than Miller-Payne 5 with ypN0 group. High TILs were significantly associated with better DFS and OS in patients with Miller-Payne 4 and ypN0 (both p = 0.016). Spatially, detected by multiplexed ion beam imaging by the time of flight combined with proteomics, tumors assessed as Miller-Payne 4 and ypN0 with good prognosis exhibited an inflamed phenotype, with dominant CD8+ T cells on tumor center, few scattered CD68+ myeloid-derived cells far away from T cells, and deposit of increased activated molecules of lymphocyte. While those with poor prognoses presented excluded phenotypes, with few CD8+ T cells restricted to invasive margins and a high density of CD14+CD68+CD11c+ myeloid cells. A good classifier model based on 29 spatial immunophenotypes was established by the random forest algorithm (AUC = 0.975), for identifying patients with Miller-Payne 4 and ypN0 who had favorable prognoses. We also observed similar signatures in patients with Miller-Payne 5 and ypN0. Taken together, spatial immunophenotypes may assess the prognosis in TNBC patients with Miller-Payne 4 and ypN0 after NACT.

Impact of glucocorticoids on the efficacy of neoadjuvant chemoradiotherapy and survival of patients with locally advanced rectal cancer: a retrospective study

sBackgroundPreclinical studies suggest that glucocorticoids (GCs) promote the proliferation and development of colorectal cancer. Because GCs are broadly prescribed for treatment-related adverse events in patients with locally advanced rectal cancer (LARC) receiving neoadjuvant chemoradiotherapy (NCRT), it’s essential to assess the effect of GCs on clinical outcomes.MethodsLARC cases treated with NCRT followed by surgery were assessed retrospectively. Evaluation of the relationship between GCs use (GCs vs. non-GCs) and neoadjuvant rectal (NAR) score (as a three-level categorical dependent variable) was performed using multivariable multinomial logistic regression (MLR). We also examined the relationship between the accumulated dose of GCs and NAR using multivariate MLR. Survival analysis of disease-free survival (DFS) and overall survival (OS) was performed using the Kaplan–Meier method. Multivariate Cox regression was used to assess confounding factors that could influence OS and DFS.ResultsThis retrospective cohort study included 790 patients with newly diagnosed non-metastatic LARC (T3-4/N + M0) who received NCRT followed by surgery between January 2012 and April 2017. The end of the follow-up period was May 11, 2022. Among the 790 patients with LARC, 342 (43.2%) received GCs treatment and 448 (56.8%) did not during the NCRT-to-surgery period. GCs medication was significantly different between mid-NAR (8–16) and low-NAR (< 8) (odds ratio [OR], 0.615; 95% CI, 0.420–0.901; P = 0.013), and the high-NAR (> 16) and low-NAR (0.563; 0.352–0.900; 0.016). Patients exposed to GCs, had a decreased 5-year OS (GCs vs. non-GCs = 80.01% (95% CI, 75.87%–84.37%) vs. 85.30% (82.06%–88.67%), P = 0.023) and poorer 5-year DFS (73.99% (69.45%–78.82%) vs. 78.7% (75.14%–82.78%), P = 0.045). The accumulated dose of GCs was an independent risk factor for OS (hazard ratio [HR], 1.007 [1.001–1.014], 0.036) and DFS (1.010 [1.004–1.017], 0.001).Conclusions and relevanceOur study revealed that GCs were associated with reduced efficacy of NCRT and worse clinical outcomes in patients with LARC during the NCRT-to-surgery period.

Diastole/Body Mass Index Ratio Can Predict Post-Thoracoscopic Surgery Metastasis in Stage I Lung Adenocarcinoma.

According to recent animal models for lung adenocarcinoma metastasis, cardiac function may be related to the clinical outcome. The aim of this study is to identify a predictable index for postoperative metastasis (POM) that is associated with cardiac function. Two hundred and seven consecutive patients who underwent thoracoscopic resection for stage I lung adenocarcinoma were included. Disease-free survival (DFS), overall survival (OS), and patients' clinical and pathological characteristics were analyzed. Among the 207 patients, 17 cases demonstrated metastasis, 110 cases received a preoperative echocardiogram, and six cases had POM. Mitral valve peak A velocity, which is one of the left ventricular diastolic function parameters affected by BMI (MVPABMI), was associated with a negative factor for POM (hazard ratio (HR): 2.139, p = 0.019) and a poor 5-year DFS in the above median (100% vs. 87%, p = 0.014). The predictable rate increased from 30.7% to 75% when the MVPABMI was above the median = 3.15 in the solid subtype). MVPABMI is a novel index for POM prediction in early-stage lung adenocarcinoma. This is a pilot study and the first attempt at research to verify that the diastole and the BMI may be associated with POM in early-stage lung adenocarcinoma.

Inflammatory and Nutritional Status Influences Outcomes of Minimally Invasive Esophagectomy.

The potential association between severe postoperative complications (SPC) and the oncological outcomes of esophageal squamous cell carcinoma (ESCC) patients according to the different Naples Prognostic Score (NPS) of the inflammatory nutritional status after minimally invasive esophagectomy (MIE) is unclear. Kaplan-Meier survival analysis was used to evaluate overall survival (OS) and disease-free survival (DFS) between with or without SPC (Clavien-Dindo grade ≥ III) in low NPS status (NPS = 0 or 1) and high NPS status (NPS = 2 or 3 or 4) patients. Cox multivariable analysis was carried out to analyze the various independent factors of OS and DFS, and a nomogram based on SPC was established. A total of 20.7% (125/604) ESCC patients developed SPC after MIE. Patients with SPC exhibited poor 5-year OS and DFS compared to those without SPC (all P < 0.001). Further analysis revealed that SPC significantly reduced OS and DFS in patients with high NPS status (all P < 0.001) but had little effect on the prognosis of patients with low NPS status (all P > 0.05). Multivariable Cox analysis revealed that SPC could be an independent influence indicator for OS and DFS in patients with high NPS status. Therefore, a novel nomogram combining SPC and tumor-node-metastasis (TNM) staging has been developed, which was found to be relatively more accurate in predicting OS and DFS than TNM staging alone. Severe complications can adversely affect the long-term oncological outcome of ESCC patients with high systemic inflammatory response and malnutrition after MIE.

Perineural Invasion Predicts Local Recurrence and Poor Survival in Laryngeal Cancer.

(1) Background: Perineural invasion (PNI) in head and neck cancer is associated with a poor prognosis; however, the effect of PNI on the prognosis of laryngeal cancer remains under debate. This retrospective study aimed to investigate the effect of PNI in fresh or salvaged larynges on survival in patients who had undergone laryngectomy for squamous cell carcinoma. (2) Methods: This study enrolled 240 patients diagnosed with laryngeal cancer who had undergone open surgery at Seoul St. Mary's Hospital, Korea. The effects of PNI, other histopathologic factors, and treatment history on survival and recurrence patterns were assessed. (3) Results: PNI was observed in 30 of 240 patients (12.5%). PNI (HR: 3.05; 95% CI: 1.90-4.88; p = 0.01) was a significant predictor of poor 5-year disease-free survival. In fresh cases, preepiglottic invasion (HR: 2.37; 95% CI: 1.45-3.88; p = 0.01) and PNI (HR: 2.96; 95% CI: 1.62-2.96; p = 0.01) were negative prognostic factors for 5-year disease-free survival. In the salvage group, however, only PNI (HR: 2.74; 95% CI: 1.26-5.92; p = 0.01) was a significant predictor of disease-free survival. Further, PNI significantly influenced high local recurrence (HR: 5.02, 95% CI: 1.28-9.66; p = 0.02). (4) Conclusions: Independent of treatment history, PNI is a prognostic factor for poor survival and local recurrence in laryngeal cancer.

The feasibility of proteomics sequencing based immune-related prognostic signature for predicting clinical outcomes of bladder cancer patients

BackgroundBladder cancer (BCa) shows its potential immunogenity in current immune-checkpoint inhibitor related immunotherapies. However, its therapeutic effects are improvable and could be affected by tumor immune microenvironment. Hence it is interesting to find some more prognostic indicators for BCa patients concerning immunotherapies.MethodsIn the present study, we retrospect 129 muscle-invasive BCa (MIBC) patients with radical cystectomy in Shanghai General Hospital during 2007 to 2018. Based on the results of proteomics sequencing from 9 pairs of MIBC tissue from Shanghai General Hospital, we focused on 13 immune-related differential expression proteins and their related genes. An immune-related prognostic signature (IRPS) was constructed according to Cancer Genome Atlas (TCGA) dataset. The IRPS was verified in ArrayExpress (E-MTAB-4321) cohort and Shanghai General Hospital (General) cohort, separately. A total of 1010 BCa patients were involved in the study, including 405 BCa patients in TCGA cohort, 476 BCa patients in E-MTAB-4321 cohort and 129 MIBC patients in General cohort.ResultIt can be indicated that high IRPS score was related to poor 5-year overall survival and disease-free survival. The IRPS score was also evaluated its immune infiltration. We found that the IRPS score was adversely associated with GZMB, IFN-γ, PD-1, PD-L1. Additionally, higher IRPS score was significantly associated with more M2 macrophage and resting mast cell infiltration.ConclusionThe study revealed a novel BCa prognostic signature based on IRPS score, which may be useful for BCa immunotherapies.

Albumin/fibrinogen ratio, a predictor of chemotherapy resistance and prognostic factor for advanced gastric cancer patients following radical gastrectomy

BackgroundThe objective of this study was to investigate potential predictors of chemotherapy resistance in patients with advanced gastric cancer (GC) following radical gastrectomy.MethodsEligible stage II/III GC patients with adjuvant chemotherapy after radical gastrectomy were enrolled in this study. A receiver operating characteristic (ROC) curve analysis was performed to assess the predictive and optimal cut-off values of continuous variables for chemotherapy resistance. Potential risk factors for chemotherapy resistance were determined with binary univariate and multivariate analyses. Potential prognostic factors for overall survival (OS) were determined by COX regression analysis. The association between survival and AFR level was examined using the Kaplan–Meier curve analysis.ResultsA total of 160 patients were included in the data analysis, and 41 patients achieved chemotherapeutic resistance with an incidence of 25.6%. Pretreatment albumin/fibrinogen ratio (AFR) (cut-off value: 10.85, AUC: 0.713, P < 0.001) was a predictor for chemotherapeutic resistance by ROC curve analysis. Low AFR (< 10.85) was an independent risk factor of chemotherapeutic resistance as determined by the univariate and multivariate logistic regression analyses (OR: 2.55, 95%CI: 1.21–4.95, P = 0.005). Multivariate COX regression analyses indicated low AFR as a prognostic factor for 5-year OS (HR: 0.36, 95%CI: 0.15–0.73, P = 0.011). Low AFR was associated with poorer 5-year disease-free survival and overall survival.ConclusionsThis study indicated that a low level of pretreatment AFR could serve as an independent predictor of chemotherapy resistance and postoperative prognosis in GC patients following radical gastrectomy.

The Safety and Feasibility of Laparoscopic Surgery for Very Low Rectal Cancer: A Retrospective Analysis Based on a Single Center’s Experience

In this work we intend to validate the long-term oncologic outcomes for very low rectal cancer over the past 20 years and to determine whether laparoscopic procedures are useful options for very low rectal cancer. A total of 327 patients, who electively underwent laparoscopic rectal cancer surgery for a lesion within 5 cm from the anal verge, were enrolled in this study and their long-term outcomes were reviewed retrospectively. Of 327 patients, 70 patients underwent laparoscopic low anterior resection (LAR), 164 underwent laparoscopic abdominal transanal proctosigmoidocolectomy with coloanal anastomosis (LATA), and 93 underwent laparoscopic abdominoperineal resection (APR). The conversion rate was 1.22% (4/327). The overall postoperative morbidity rate was 26.30% (86/327). The 5-year disease free survival (DFS), 5-year overall survival (OS), and 3-year local recurrence (LR) were 64.3%, 79.7%, and 9.2%, respectively. The CRM involvement was a significant independent factor for DFS (p = 0.018) and OS (p = 0.042) in multivariate analysis. Laparoscopic APR showed poorer 5-year DFS (47.8%), 5-year OS (64.0%), and 3-year LR (17.6%) than laparoscopic LAR (74.1%, 86.4%, 1.9%) and laparoscopic LATA (69.2%, 83.6%, 9.2%). Laparoscopic procedures for very low rectal cancer including LAR, LATA, and APR could be good surgical options in selective patients with very low rectal cancer.

The mechanism of miR-410-3p and miR-34c in nasopharyngeal carcinoma development and progression.

To investigate the relationship between miR-410-3p, miR-34c and nasopharyngeal carcinoma development, we detected the expression of miR-410-3p and miR-34c in nasopharyngeal carcinoma tissues and evaluate its clinical value as a molecular marker for predicting the prognosis in patients with nasopharyngeal carcinoma through clinical case study. To identify the role and mechanism of miR-410-3p and miR-34c in nasopharyngeal carcinoma development and progression. The expression of miR-410-3p and miR-34cin 300 cases of nasopharyngeal carcinoma tissues and 30 cases of paired adjacent normal breast tissues was detected by RT-qPCR. The paired t-test was used to compare the differences of miR-410-3pand miR-34c levels between the nasopharyngeal carcinoma and normal groups. The Chi-square test was used to compare the differences between miR-410-3p and miR-34c expression and clinicopathological factors. The Kaplan-Meier survival curve was used to analyze the relationship between miR-410-3p and miR-34c expression and 5-year overall survival (OS). The Cox proportional hazards regression model was used to evaluate the prognostic value. The results were validated by TCGA database. The expression of miR-410-3p was down-regulated in nasopharyngeal carcinoma tissues compared with that of paired normal tissues (P<0.001). The patients with lower miR-410-3p expression have a higher ratio of positive lymph node status (P=0.039) and a poorer 5-year disease-free survival (P=0.001) and 5-year overall survival (P = 0.002). The expression of mi R-34c was down-regulated in nasopharyngeal carcinoma tissues compared with that of paired normal tissues (P<0.001). Up-regulation of the miR-34c inhibited the viability of paired normal tissues (P<0. 01), but there was no significant change in migration of the paired normal tissues. Downregulation of mi R-34c promoted the viability and migration of paired normal tissues (P<0. 05). The expression of miR-410-3p and miR-34c levels are predictors for the OS in patients with nasopharyngeal carcinoma. The expression of miR-410-3p and miR-34c are molecular markers of early nasopharyngeal carcinoma metastasis and an independent prognostic biomarker for patients with nasopharyngeal carcinoma.

Association of sarcopenia and expression of interleukin-23 in colorectal cancer survival

The relationship between sarcopenia and interleukin-23 (IL-23) has not been reported. We designed this study to investigate this relationship and the association of sarcopenia and interleukin-23 with poor prognosis of colorectal cancer. We used the %FINDCUT SAS macro to determine the cutpoints of the skeletal muscle index (SMI) to define sarcopenia in colorectal cancer patients. Immunohistochemical staining was performed to detect high and low IL-23 expression in cancer samples. Clinicopathological features were also recorded. The prognosis of the 5-year disease-free survival and overall survival were analyzed using univariate and multivariate methods. A total of 114 patients with colorectal cancer were enrolled. The mean age was 63.2 years. Forty-six (40%) patients were female. Sarcopenia was defined as less than 50cm2/m2 for men and 32cm2/m2 for women and 52(46%) patients were defined as having sarcopenia. Sarcopenia was significantly associated with poor 5-year disease-free survival and overall survival (p=0.003 and p=0.001, respectively). Multivariate adjustment demonstrated that sarcopenia was an independent predictor of the 5-year disease-free survival (hazard ratio=1.827, p=0.024) and overall survival (hazard ratio=3.669, p<0.001). A lower SMI was detected in patients with high IL-23 expression (p=0.045). After grouping the patients with sarcopenia and IL-23 expression, the patients with sarcopenia and high IL-23 expression had the worst disease-free survival (p=0.013) and overall survival (p=0.007). This is the first study to explore the significant association between IL-23 expression and sarcopenia in colorectal cancer. Sarcopenia combined with IL-23, as an inflammatory marker, significantly predicted poor survival.

The Genomic Landscape of Radioactive Iodine Refractory and Avid Papillary Thyroid Carcinomas

Background: Although, standard treatment of Papillary Thyroid Carcinoma (PTC), involving surgery followed by radioactive iodine (RAI) therapy, is curative for most patients, 5-20% of patients develop RAI refractory disease. The repertoire of genomic events enabling RAI refractory disease in PTC needs elucidating. Methods: Whole-exome sequencing was performed on 100 primary PTC tumours, consisting of 47 RAI refractory and 53 RAI avid tumours, with matched germline. The resulting somatic variants were analysed to compare the genomic landscape, driver events and clinically actionable events between RAI refractory and avid PTC. Results: RAI refractory primary tumours were significantly associated with later stage, positive involvement of surgical margins, presence of extrathyroidal extension, lymph node metastases and poorer 5-year disease-free survival. Mutational burden was significantly higher, with additional subclonal mutations in RAI refractory compared to avid PTC patients. RAI refractory primary tumours showed significantly stronger PD-L1 expression. Mutations and PD-L1 expression in RAI Refractory PTC tumours significantly correlated with mutational signatures related to defective DNA base and nucleotide excision repair pathways. Driver mutations were acquired earlier in RAI refractory than in avid primary tumours. Conclusions: We conclude that RAI refractoriness is gained early in PTC, and is significantly associated with a higher mutational burden, PD-L1 expression, and mutational signatures, which may serve as important prognostic factors and indicate suitability for treatment with immune checkpoint inhibitors.

MACC1 Is Associated With Epithelial-Mesenchymal Transition and Can Predict Poor Prognosis in Nasopharyngeal Carcinoma.

BackgroundGiven the reported correlation between the oncogene metastasis-associated in colon cancer 1 (MACC1) and nasopharyngeal carcinoma (NPC), as well as between MACC1 and epithelial–mesenchymal transition (EMT), we speculated that EMT is a likely causative link between MACC1 expression and poor NPC prognosis. Thus, we aim to clarify the relationship between MACC1 and EMT in NPC prognosis.Material and MethodsWe performed immunohistochemical examination of tissue sections from 128 NPC patients that were divided into six groups corresponding to high and low protein expression of MACC1 and two EMT-related proteins, vimentin and E-cadherin, and Kaplan–Meier (KM) survival analyses were performed.ResultsKM survival analysis showed that upregulation of MACC1 and vimentin and downregulation of E-cadherin were significantly associated with reduced survival in NPC. Short hairpin RNA (shRNA) interference and immunoblotting in the NPC cell line HNE-1 led to increased E-cadherin but decreased vimentin levels. MACC1 overexpression was significantly correlated with poor 5-year overall survival, metastasis-free survival, and disease-free survival (P<0.05) but not with poor relapse-free survival (P>0.05). Univariate analyses revealed that MACC1, E-cadherin, and vimentin levels along with T and N tumor classifications and cancer staging are significant prognostic factors of NPC (P<0.05).ConclusionOur findings showed the association between MACC1 and EMT in NPC malignancy and support the role of MACC1 as a prognostic biomarker and molecular target for NPC treatment.

ATAD3A stabilizes GRP78 to suppress ER stress for acquired chemoresistance in colorectal cancer.

AAA domain containing 3A (ATAD3A) is a nucleus-encoded mitochondrial protein with vital function in communication between endoplasmic reticulum (ER) and mitochondria which is participated in cancer metastasis. Here we show that elevated ATAD3A expression is clinically associated with poor 5-year disease-free survival in patients with colorectal cancer (CRC), especially high-risk CRC patients who received adjuvant chemotherapy. Our results indicated ATAD3A is significantly upregulated to reduce chemotherapy-induced cancer cell death. We found that knockdown of ATAD3A leads to dysregulation in protein processing for inducing ER stress by RNA sequencing (RNA-seq). In response to chemotherapy-induced ER stress, ATAD3A interacts with elevated GRP78 protein to assist protein folding and alleviate ER stress for cancer cell survival. This reduction of ER stress leads to reduce the surface exposure of calreticulin, which is the initiator of immunogenic cell death and antitumor immunity. However, silencing of ATAD3A enhances cell death, triggers the feasibility of chemotherapy-induced ER stress for antitumor immunity, increases infiltration of T lymphocytes and delays tumor regrowth in vitro and in vivo. Clinically, CRC patients with less ATAD3A have high density of CD45+ intratumoral infiltrating lymphocytes (TILs) and memory CD45RO+ TILs. Taken together, our results suggest that pharmacologic targeting to ATAD3A might be a potential therapeutic strategy to enhance antitumor immunity for CRC patients who received adjuvant chemotherapy.

Cigarette smoking promotes keratinocyte malignancy via generation of cancer stem-like cells.

Objectives: Cigarette smoking is involved in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). However, the underlying molecular mechanisms of cigarette smoking-induced HNSCC carcinogenesis are unclear and may involve cancer stem-like cell generation. We examined the effects of cigarette smoke condensate (CSC) on the formation of cancer stem-like cells, which are rich in octamer-binding transcription factor (OCT)-4, inhibitor of differentiation 1 (ID1), nuclear factor (NF)-κB, and B lymphoma Mo-MLV insertion region 1 homolog (BMI-1).Materials and Methods: We used in vitro, in vivo, and archival human HNSCC tissue analysis to evaluate the effects of CSC on cancer stem-like cell formation.Results: We found that CSC regulated OCT-4 expression, which subsequently regulated ID1 and NF-κB, at the promoter, mRNA, and protein levels in vitro. Furthermore, OCT-4 knockdown with siRNA reduced ID1 expression. ID1 and NF-κB synergistically increased the expression of BMI-1 and stimulated keratinocyte sphere generation. In vivo, ID1 and NF-κB acted together to generate malignant xenograft tumors, which were aggressive locally and systemically metastatic. Clinical data confirmed that ID1- and NF-κB-positive patients had poor clinical outcomes and 5-year disease-free survival.Conclusion: Our data suggest that smoking cigarettes promoted cancer stem-like cell generation in the head and neck area via the OCT-4/ID1/NF-κB/BMI-1 signaling pathway.

Clinical significance of pretreatment prognostic nutritional index and lymphocyte-to-monocyte ratio in patients with advanced p16-negative oropharyngeal cancer-a retrospective study.

BackgroundSystemic inflammation and nutritional status both play roles in the survival of cancer patients. Therefore, it is important to understand the effects of prognostic nutritional index (PNI) and lymphocyte-to-monocyte ratio (LMR) on the survival of patients with advanced p16-negative oropharyngeal cancer.MethodsA total of 142 patients diagnosed with advanced p16-negative oropharyngeal cancer between 2008 and 2015 were enrolled in this study. All patients received primary treatment with definite concurrent chemoradiotherapy (CCRT). Optimal cutoff values for PNI and LMR were determined using receiver operating characteristic curves for survival prediction. Survival rates for different level of PNI and LMR were estimated and compared using Kaplan–Meier method and log-rank test to see if there were significant effects on these end points, including 5-year overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) rates. The effects of PNI and LMR on survival were assessed using Cox regression model adjusted for other prognostic factors.ResultsThe results showed the optimal cutoff values for PNI and LMR were 50.5 and 4.45, respectively. A high PNI (≧50.5) was significantly improved the 5-year OS. A low LMR (<4.45) was significantly associated with a poor 5-year DFS, DSS, and OS. In multivariate analysis, both PNI and LMR were independent prognosticators for 5-year OS.ConclusionsElevated pretreatment PNI and LMR are both favorable prognosticators in advanced p16-negative oropharyngeal cancer patients undergoing CCRT.

Pretreatment Albumin-to-Fibrinogen Ratio Independently Predicts Chemotherapy Response and Prognosis in Patients with Locally Advanced Rectal Cancer Undergoing Total Mesorectal Excision After Neoadjuvant Chemoradiotherapy.

BackgroundNeoadjuvant chemoradiotherapy (nCRT) followed by surgery of total mesorectal excision (TME) is currently accepted as the standard treatment for locally advanced rectal cancer (LARC). This study aimed to investigate the potential prognostic factors, including the albumin-to-fibrinogen ratio (AFR) for LARC patients.MethodsWe retrospectively recruited LARC patients (cT3-4 and/or cN1-2) who underwent nCRT followed by TME between January 2011 and January 2015. The cut-off value of pretreatment AFR for overall survival (OS) was determined by the receiver operating characteristic (ROC) curve. The potential predictive factors for prognosis in the LARC patients were assessed by the univariate and multivariate Cox’s proportional hazard regression and Kaplan–Meier curve analyses.ResultsAFR was a significant predictor for OS with a cut-off value of 8.65 and an AUC of 0.882 (P<0.001). The pretreatment AFR level was the only independent risk factor for pathologic response to nCRT (HR: 2.44, 95% CI: 1.43–4.17, P=0.003), 5-year OS (HR: 3.31, 95% CI: 1.51–6.77, P=0.005) and disease-free survival (DFS) (HR: 2.73, 95% CI: 1.34–5.47, P=0.007) in LARC patients. A low pretreatment AFR level was significantly associated with a poor 5-year OS and DFS by the Log rank test (P=0.003 and 0.006, respectively).ConclusionPretreatment AFR level was an independent prognostic factor in LARC patients undergoing TME after nCRT.

Comparative study on the oncological prognosis of laparoscopy and laparotomy for stage IIA1 cervical squamous cell carcinoma

ObjectiveTo compare the 5-year overall survival (OS) and disease-free survival (DFS) rate of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for stage IIA1 cervical squamous cell carcinoma. MethodsBased on a large database containing information on the clinical diagnosis and treatment of cervical cancer in China, the oncological outcomes of the two surgical approaches for stage IIA1 cervical squamous cell carcinoma were compared after 1:2 propensity score matching (PSM). ResultsAfter 1:2 propensity score matching (PSM), 510 patients were included in the LRH group, and 999 patients were included in the ARH group. LRH showed a similar 5-year OS but a lower DFS rate (81.3% vs. 87.4%, P = 0.018) than ARH. In the multivariate analysis, LRH was identified as an independent risk factor for worse 5-year DFS (HR = 1.569, 95% CI: 1.131–2.176, P = 0.007). Among patients with a tumour size <2 cm, the LRH and ARH groups showed similar OS and DFS rates after 1:2 PSM, and multivariate analysis showed that the surgical approach was not an independent risk factor affecting the OS or DFS rate. Among patients with a tumour size ≥2 cm and <4 cm, there was no difference in OS between the LRH and ARH groups after matching, but the DFS in the LRH group was significantly lower than that in the ARH group (81.1% vs 86.2%, P = 0.034). In the multivariate analysis, the laparoscopic approach was not associated with OS but was independently associated with worse DFS (HR = 1.546, 95% CI: 1.094–2.185, P = 0.014). ConclusionsLRH was associated with poorer 5-year DFS than ARH in patients with stage IIA1 cervical squamous cell carcinoma. However, LRH showed 5-year OS and DFS rates similar to those of ARH among patients with a tumour size <2 cm. For patients with a tumour size ≥2 cm and <4 cm, LRH showed a lower DFS rate than ARH.

Prognostic value of pretreatment systemic inflammatory markers in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy

The aim of this study was to explore the most powerful systemic inflammation marker of survival in locally advanced rectal cancer (LARC) patients and construct prognostic nomograms. A total of 472 LARC patients undergoing neoadjuvant chemoradiotherapy (NCRT) and radical surgery from 2011 to 2015 were included. The optimal cutoff points for the systemic immune-inflammation index (SII); and neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and monocyte-to-lymphocyte (MLR) ratios were calculated and determined by using the X-tile program. The cut-off values were 797.6. 2.3, 169.5, and 0.4, respectively. Cox regression analysis demonstrated that higher pathological TNM stage, the AJCC tumor regression grade, and the NLR level were significantly associated with increased overall survival and disease-free survival. High NLR level (≥ 2.3) was associated with higher pre-NCRT CA19–9 levels, lower hemoglobin, larger tumor size, and more lymph nodes retrieved (p = 0.012, p = 0.024, and p < 0.001; p < 0.001, respectively). High NRL scores were associated with poorer 5-year disease-free survival and overall survival (p < 0.001, and p < 0.001, respectively). Predictive nomograms and time-independent receiver operating characteristic (ROC) curve that included the NLR score group were superior to those without NLR scores. Higher NLR scores (≥2 0.3) were associated with poorer DFS and OS in LARC patients. In addition, NLR was identified as the most effective marker for systemic inflammation, and the prognostic value was further confirmed by time-dependent ROC analysis. More intense adjuvant treatment could be considered for higher NLR score patients with LARC following NCRT.

Clinicopathological Characteristics and Clinical Outcome in Egyptian Female Breast Cancer Patients With and Without BRCA1/2 Mutations

Introduction: Germline mutations in BRCA1 and BRCA2 genes confer high risk of developing breast cancer. We sought to examine whether the clinicopathological characteristics and the clinical outcome differ in patients with and without BRCA mutations. Patients and Methods: A series of 103 Egyptian female patients were recruited from Breast Cancer Unit, Clinical Oncology Department, Ain Shams University, Egypt. The enrolled patients, unselected for age of onset or family history, were tested for BRCA1/2 mutations using HRM analysis and direct sequencing. The clinical and pathological features of the patients were retrospectively assessed and comparisons were made using Chi-square. Disease free survival (DFS) was estimated by Kaplan–Meier method and compared in the two groups with log-rank. Results: The overall rate of BRCA1/2 mutations was 44%. Novel deleterious mutations were detected and submitted to NCBI Clinvar database. Deleterious mutations were identified in 29 cases and unclassified variants in 32 cases, 15 of which had a co-occuring deleterious mutation. Patients with BRCA mutations tended to have early onset breast cancer compared to non-carriers ( P=0.002), more often premenopausal ( P=0.006), with a familial history of breast cancer as well as other cancers ( P=0.005). BRCA-related breast cancers were more likely to have T3-T4 stage than wild type (41% versus 28%, P=0.02), positive lymph node involvement (78 versus 53%, P=0.007) and develop bilateral breast cancers (24% versus 9%, P =0.007). The incidence of ER negative and PR negative tumors was higher in BRCA carriers, but not statistically significant ( P=0.17 and 0.15, respectively). No difference in HER-2/ neu status was observed ( P=0.25). Early age at onset, positive lymph node involvement, family history of any cancer were independent predictive factors for occurrence of BRCA1/2 mutations. The median follow-up time for the cohort was 5.53 years. Patients with BRCA mutations had poorer 5-year DFS compared to non-carriers (47.7% versus 67.4%, P=0.041); but Cox regression analysis failed to demonstrate a significant independent influence of BRCA mutation status on DFS. Conclusion: This study shows that BRCA-related breast cancers in the Egyptian population have distinctive clinical and tumor features as well as outcome. This data has important health implications for guiding cancer control policies.