Prognostic Factor For 5-year Disease-free Survival Research Articles

HPV status and immunohistochemical analysis of p16, p53 and PD‑L1 expression as prognostic biomarkers in patients with squamous cell anal cancer receiving definitive radiotherapy/chemoradiotherapy.

Anal squamous cell carcinoma (SCC) treated with definitive radiotherapy (RT)/chemoradiotherapy (CRT) has shown high success rates, yet challenges such as treatment resistance and recurrence persist. The present study aimed to investigate the associations between immunohistochemical (IHC) evaluation, treatment response and prognosis in anal SCC. A retrospective cohort analysis included 42 patients with anal SCC treated at a single institution between 2006 and 2022. Human papillomavirus (HPV) status was determined, and the IHC analysis of p16, p53 and PD-L1 expression was conducted using formalin-fixed, paraffin-embedded biopsies. A complete response to RT/CRT was observed in 71.4% of patients. Recurrence occurred in 38.1% of cases, of which 7.1% had local-regional recurrence (LRR), 14.3% had distant recurrence (DR), and 16.7% had both LRR and DR. HPV positivity (71.4%) was significantly associated with p16 positivity. Lack of complete response was associated with HPV-negative status, p16-negative status, increased recurrence and DR. In addition, recurrence was significantly associated with p53-positive status, and p53 positivity was significantly associated with increased LRR. PD-L1 positivity, defined as a combined positive score (CPS) ≥1% was found in 73.8% of the patients, and exhibited significant associations with HPV positivity and p16 positivity. PD-L1 CPS ≥ 1% was also associated with an increased LRR. Univariate analysis revealed that age <65 years, a complete response and HPV positivity were associated with increased 5-year overall survival (OS), while a complete response, HPV positivity and p53-negative status were associated with increased 5-year disease-free survival (DFS). Multivariate analysis identified that age <65 years and HPV positivity are independent prognostic factors for 5-year OS, and a complete response and p53-negative status are independent prognostic factors for 5-year DFS. In conclusion, these findings suggust that the identification of HPV status and poor prognostic biomarkers at diagnosis may be used to guide personalized treatment strategies, with the combination of immunotherapy with standard CRT potentially providing improved outcomes.

Prognostic value of tumor necrosis based on the evaluation of frequency in invasive breast cancer

BackgroundTumor necrosis (TN) was associated with poor prognosis. However, the traditional classification of TN ignored spatial intratumor heterogeneity, which may be associated with important prognosis. The purpose of this study was to propose a new method to reveal the hidden prognostic value of spatial heterogeneity of TN in invasive breast cancer (IBC).MethodsMultiphoton microscopy (MPM) was used to obtain multiphoton images from 471 patients. According to the relative spatial positions of TN, tumor cells, collagen fibers and myoepithelium, four spatial heterogeneities of TN (TN1-4) were defined. Based on the frequency of individual TN, TN-score was obtained to investigate the prognostic value of TN.ResultsPatients with high-risk TN had worse 5-year disease-free survival (DFS) than patients with no necrosis (32.5% vs. 64.7%; P < 0.0001 in training set; 45.8% vs. 70.8%; P = 0.017 in validation set), while patients with low-risk TN had a 5-year DFS comparable to patients with no necrosis (60.0% vs. 64.7%; P = 0.497 in training set; 59.8% vs. 70.8%; P = 0.121 in validation set). Furthermore, high-risk TN “up-staged” the patients with IBC. Patients with high-risk TN and stage I tumors had a 5-year DFS comparable to patients with stage II tumors (55.6% vs. 62.0%; P = 0.565 in training set; 62.5% vs. 66.3%; P = 0.856 in validation set), as well as patients with high-risk TN and stage II tumors had a 5-year DFS comparable to patients with stage III tumors (33.3% vs. 24.6%; P = 0.271 in training set; 44.4% vs. 39.3%; P = 0.519 in validation set).ConclusionsTN-score was an independent prognostic factor for 5-year DFS. Only high-risk TN was associated with poor prognosis. High-risk TN “up-staged” the patients with IBC. Incorporating TN-score into staging category could improve its performance to stratify patients.

Effect of modified no-touch laparoscopic radical hysterectomy on outcomes of early stage cervical cancer: A retrospective cohort study.

ObjectivesWe aimed to compare the prognosis of modified no‐touch laparoscopic radical hysterectomy (MLRH) and laparoscopic radical hysterectomy (LRH) on survival in patients with early stage cervical cancer.Materials and MethodsThe clinicopathological data of patients with stage IB1 and IIA1 cervical cancer, who underwent radical surgery between 2014 and 2019, were retrospectively reviewed. The 5‐year disease‐free survival (DFS) and overall survival (OS) were compared between the MLRH and LRH groups using the Kaplan–Meier method. Independent prognostic factors for 5‐year DFS and OS were identified using multivariate, forward, stepwise Cox proportional hazards regression models.ResultsA total of 223 patients with stage IB1 and IIA1 cervical cancer were included. Kaplan–Meier analysis revealed that the 5‐year DFS and OS rates in the MLRH (n = 81) group were significantly higher than those in the LRH group (n = 142) (DFS, 94.5% vs. 78.8%, p = 0.007; OS, 96.7% vs. 87.6%, p = 0.033). No significant differences were identified between the two groups in terms of operative time, blood loss, transfusion requirement, and intraoperative or postoperative complications. MLRH was an independent prognostic factor associated with increased 5‐year DFS (adjusted hazard ratio [HR], 0.202; 95% confidence interval [CI], 0.069–0.594; p = 0.004) and 5‐year OS (adjusted HR, 0.163; 95% CI, 0.035–0.748; p = 0.020).ConclusionThe oncologic outcomes were superior with MLRH than with LRH in patients with stage IB1 and IIA1 cervical cancer. Contact of cervical tumor cells with the pelvic cavity likely explains the worse prognosis associated with LRH.

Survival outcomes of women with grade 3 endometrioid endometrial cancer: the impact of adjuvant treatment strategies

This multicenter investigation was performed to evaluate the adjuvant treatment options, prognostic factors, and patterns of recurrence in patients with grade 3 endometrioid endometrial cancer (G3-EEC). The medical reports of patients undergoing at least total hysterectomy and salpingo-oophorectomy for G3-EEC between 1996 and 2018 at 11 gynecological oncology centers were analyzed. Optimal surgery was defined as removal of all disease except for residual nodules with a maximum diameter ≤ 1cm, as determined at completion of the primary operation. Adequate systematic lymphadenectomy was defined as the removal of at least 15 pelvic and at least 5 paraaortic LNs. The study population consists of 465 women with G3-EEC. The 5-year disease-free survival (DFS) and overall survival (OS) rates of the entire cohort are 50.3% and 57.6%, respectively. Adequate systematic lymphadenectomy was achieved in 429 (92.2%) patients. Optimal surgery was achieved in 135 (75.0%) patients in advanced stage. Inadequate lymphadenectomy (DFS; HR 3.4, 95% CI 3.0-5.6; P = 0.016-OS; HR 3.2, 95% CI 1.6-6.5; P = 0.019) was independent prognostic factors for 5-year DFS and OS. Inadequate lymphadenectomy and LVSI were independent prognostic factors for worse DFS and OS in women with stage I-II G3-EEC. Adequate lymphadenectomy and optimal surgery were independent prognostic factors for better DFS and OS in women with stage III-IV G3-EEC.

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.

Preoperative Anemia as a Prognostic Factor in Endometrioid-Type Endometrial Carcinoma.

This study sought to determine the frequency of preoperative anemia (hemoglobin level <12 g/dL) and its prognostic significance for clinicopathological factors and survival outcomes in Saudi patients with endometrioid-type endometrial carcinoma (EC). A retrospective cross-sectional study was conducted at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. A total of 148 patients who underwent staging surgery for primary EC were retrospectively analyzed for perioperative details regarding clinicopathological factors and survival. The frequency of preoperative anemia was 27.7% (n = 41). Patients with advanced FIGO disease (stages III-IV), unfavourable endometrioid tumour grade II-III, ≥50% myometrial invasion, positive lymphovascular space invasion, and tumour recurrence had statistically significant lower mean preoperative hemoglobin levels (two-tailed Mann-Whitney U test; P < 0.05). Patients with preoperative anemia had statistically significant higher rates of advanced FIGO stage III-IV (P = 0.0000), unfavourable grades II-III endometrioid histology (P = 0.0005), ≥50% myometrial invasion (P = 0.0016), positive lymphovascular space invasion (P = 0.0019), and tumour recurrence (P = 0.0064) than patients without preoperative anemia (two-tailed chi-square test). In a univariate analysis, patients with preoperative anemia had statistically lower significant mean 5-year disease-free survival (DFS) and overall survival (OS) rates than patients without preoperative anemia (log-rank test; P < 0.0001 and P < 0.0003, respectively). In a multivariate analysis, preoperative anemia was shown to be an independent prognostic factor for 5-year DFS (P = 0.0303), but not OS (P = 0.2588). In patients with endometrioid-type EC, the preoperative anemia is fairly common. Moreover, preoperative anemia is correlated with a number of unfavourable clinicopathological factors, as well as poor survival (in terms of DFS and OS) in the univariate analysis.

CXCR4, CXCL12 and the relative CXCL12-CXCR4 expression as prognostic factors in colon cancer.

The CXCL12-CXCR4 axis is proposed to mediate metastasis formation. In this study, we examined CXCL12, CXCR4 and the relative CXCL12-CXCR4 expression as prognostic factors in two cohorts of colon cancer patients. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to study CXCR4, CXCL12 and relative CXCL12-CXCR4 expression in tissue microarrays. Our study included totally 596 patients, 290 in cohort 1 and 306 in cohort 2. For tumour, node, metastasis (TNM) stage III, low nuclear expression of CXCR4 was a positive prognostic factor for 5-year disease-free survival (DFS) in cohort 1 (P = 0.007) and cohort 2 (P = 0.023). In multivariate analysis for stage III, nuclear expression of CXCR4 in cohort 1 was confirmed as a prognostic factor for DFS (hazard ratio (HR), 0.27; 95% CI, 0.09 to 0.77). For TNM stage III, high cytoplasmic expression of CXCL12 was associated with better 5-year DFS in both cohorts (P = 0.006 and P = 0.006, respectively). We further validated the positive prognostic value of CXCL12 expression for 5-year DFS in stage III with ISH (P = 0.022). For TNM stage III, the relative CXCL12-CXCR4 expression (CXCL12 > CXCR4 vs CXCL12 = CXCR4 vs CXCL12 < CXCR4) was a prognostic factor for 5-year DFS in cohort 1 (92% vs 46% vs 31%, respectively; P < 0.001) and cohort 2 (92% vs 66% vs 30%, respectively; P = 0.006). In conclusion, CXCL12 and relative CXCL12-CXCR4 expression are independent prognostic factors for 5-year DFS in TNM stage III colon cancer.

Expression of Human Epidermal Growth Factor Receptor-2 in Resected Rectal Cancer

The addition of trastuzumab to chemotherapy was demonstrated to be beneficial for advanced human epidermal growth factor receptor-2 (HER-2) positive gastric cancer. However, the HER-2 status of rectal cancer remains uncertain. This study aimed to determine the HER-2 expression in a large multicenter cohort of rectal cancer patients. The clinical and pathological features of 717 patients were retrospectively reviewed. All the patients were diagnosed with primary rectal adenocarcinoma without distant metastasis and took surgery directly without any preoperative anticancer treatment. HER-2 status was assessed on resected samples. A total of 99 cases with IHC3+ and 16 cases with IHC 2+ plus gene amplification were determined as HER-2 positive. 22.6% of HER-2 positive patients had local recurrence, whereas 16.9% of HER-2 negative patients did (P = 0.146). HER-2 positive tumors were more likely to have distant metastasis (P = 0.007). Univariate analysis revealed that pathological tumor stage, pathological node stage, positive margin, and lymphovascular invasion were significantly correlated with 5-year disease-free survival (DFS) and 5-year overall survival (OS). The patients with >10 dissected lymph nodes showed significantly longer OS (P = 0.045) but not DFS (P = 0.054). HER-2 negative patients had significantly better 5-year DFS (P < 0.001) and 5-year OS (P = 0.013) than those of the HER-2 positive patients. In the subgroup analysis for the early rectal cancer and locally advanced rectal cancer, HER-2 was also a poor predictor for survival. Multivariate analysis revealed that HER-2 was an independent prognostic factor for 5-year DFS (hazard ratio [HR] = 1.919, 95% confidence interval [CI] 1.415–2.605, P < 0.001) and for 5-year OS (HR = 1.549, 95% CI 1.097–2.186, P = 0.013). When the treatment was included in the analysis for locally advanced patients, HER-2 was a prognostic factor for 5-year DFS (P = 0.001) but not for 5-year OS (P = 0.106). This study confirmed that HER-2 was expressed in a part of patients with rectal cancers and might be used as a negative predictor. The results may support the trials to assess the efficacy of trastuzumab in treating HER-2 positive rectal cancer patients.

Lymph node ratio as an independent prognostic indicator in stage III colorectal cancer: especially for fewer than 12 lymph nodes examined.

Although nodal invasion represents one of the most powerful prognostic indicators in colorectal cancer (CRC), marked heterogeneity exists within stage III patients. Lymph node ratio (LNR) may offer more precise prognostication in stage III CRC. The aim of this study is to investigate the prognostic impact of LNR on survival in stage III CRC patients. We retrospectively reviewed the data of 288 consecutive patients who underwent radical resection for stage III CRC between January 2000 and December 2008 in the Gastrointestinal Surgery Department, Peking University People's Hospital. The patients were divided into three groups according to LNR quartiles: LNR < 0.167 (n=72), 0.167 ≤ LNR < 0.562 (n = 140), and LNR ≥ 0.562 (n=76). The association between overall survival (OS) and disease-free survival (DFS) and 11 variables including age, gender, tumor location, size, grade, histology, tumor (T) stage, number of metastatic LNs, and LNR was analyzed by multivariate analysis. Survival curves were plotted by the Kaplan-Meier method. Both LNR and the number of metastatic LNs were significant prognostic factors for 5-year DFS and OS in stage III CRC patients. LNR was an independent prognostic factor for 5-year OS. LNR remained an independent prognostic factor in patients with fewer than 12 lymph nodes examined. LNR was a potent independent prognostic predictor for OS and DFS in stage III CRC patients, especially for patients with fewer than 12 lymph nodes examined.

Efficacy of preoperative concurrent chemoradiotherapy in treatment of locally advanced middle-low rectal cancer

Objective To evaluate the efficacy and tolerance of preoperative concurrent chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer.Methods From June 2007 to June 2013,51 untreated patients with histopathologically proven rectal cancer (T3/T4 or N (+))were included in this study.Three-dimensional radiotherapy was delivered to the whole pelvic cavity at 45.0-50.4 Gy/25-28 fractions.Two cycles of chemotherapy with FOLFOX4 or XELOX were given concurrently at weeks 1 and 4 of radiotherapy.Surgery was performed at 4-8 weeks after chemoradiotherapy.Adjuvant chemotherapy with FOLFOX4 or XELOX was given within one month after surgery.The Kaplan-Meier method was used to calculate survival rates,and the log-rank test was used for univariate analysis;the Cox regression model was used for multivariate prognostic analysis.Results Fortynine patients completed the preoperative chemoradiotherapy and surgery.The median follow-up was 2.9 years.The overall sphincter preservation rate was 65％;the overall downstaging rate was 59％.Ten (20.4％) of all patients achieved a pathologic complete response (pCR).Grade ≥3 toxicities occurred in 25％ of all patients,and the overall postoperative complication rate was 31％.The 3-and 5-year sample sizes were 24,12,respectively.The 3-and 5-year overall survival rates were 81％ and 69％,respectively;the 3-and 5-year disease-free survival (DFS) rates were 76％ and 60％,respectively;the 3-and 5-year local recurrence-free survival (LRFS) rates were 78％ and 70％,respectively;the distant metastasis-free survival rates were 82％ and 74％,respectively.The multivariate analysis showed that tumor downstaging was an independent prognostic factor for 5-year DFS and LRFS.Conclusions For locally advanced middle-low rectal cancer,preoperative radiotherapy with concurrent FOLFOX4/XELOX chemotherapy can increase pathologic downstaging rate,pCR rate,and sphincter preservation rate.Patients with tumor downstaging may have a better survival advantage. Key words: Rectal neoplasms/radiochemotherapy ; Radiochemotherapy, concurrent ; Rectal neoplasms/surgery ; Downstaging; Prognosis

Expressions of key molecules affiliated cytoskeleton in laryngeal squamous cell carcinoma and their implications for prognosis

To study the expressions of key assemblies of cytoskeleton, Fascin-1, Ezrin and Paxillin, in laryngeal squamous cell carcinoma (LSCC) and their correlation with clinicopathologic characteristics, cancer recurrence and survival of patients with LSCC. The expressions of Fascin-1, Ezrin and Paxillin proteins were detected by immunohistochemistry in 199 cases of LSCC. Unconditional Logistic regression model or Cox proportional hazards model was used for the analyses of recurrent risks and prognostic factors. Significantly increased expression of Fascin-1, Ezrin or Paxillin expression was showed in the LSCC with poorly differentiated, positively cervical lymph nodal metastasis, and clinical stage III + IV respectively (P < 0.05). The expressions of three kinds of proteins in the recurrent cases were higher than those in non-recurrent cases respectively (χ(2) were 42.479, 43.673 and 22.261, P < 0.05). The highest recurrence rate (69.1%) was observed in group of cases with the highly co-expression of the three kinds of proteins (P < 0.05). The expression of Fascin-1 (OR = 7.89, 95%CI 2.26 - 27.53, P = 0.001), or Ezrin (OR = 2.51, 95%CI 1.18 - 5.32, P < 0.001) was independent risk for recurrence. Five-year disease-free survival rates of patients with high expression of Fascin-1, Ezrin or Paxillin were lower than those of patients with negative or low expressions for the proteins (P < 0.05). Patients with highly co-expression of three kinds of proteins showed the poorest survival prognosis, with a 5-year disease free survival (DFS) of only 26.4% (P < 0.05), and expressions of three proteins were independent prognostic factors for 5-year DFS (P < 0.05). Fascin-1, Ezrin, and Paxillin were correlative with LSCC progression and might be potential predictors for cancer recurrence and survival of patients with LSCC, as well as therapeutic targets for LSCC.