Independent Prognostic Factor In Stage Research Articles

The depth of perineural invasion is an independent prognostic factor for stage II colorectal cancer.

Perineural invasion (PNI) is the invasion of nerves by cancer cells and is associated with poor survival in stage II colorectal cancer. However, PNI can be further subdivided according to the depth of invasion, and the depth of PNI has not been clearly linked to prognosis. This study aimed to assess the prognostic value of different depths of PNI in stage II colorectal cancer. We defined PNI in the submucosal plexus and myenteric plexus as superficial perineural invasion (sup-PNI) and PNI in the subserous plexus as deep perineural invasion (deep-PNI). Patients were divided into three groups based on the depth of PNI: sup-PNI, deep-PNI and non-PNI. Then, univariate and multivariate Cox regression analyses were conducted to evaluate the role of PNI in the prognosis of stage II colorectal cancer. This study enrolled 3508 patients with stage II colorectal cancer who underwent resection for primary colorectal lesions between January 2013 and September 2019. Clinicopathological features, including elevated carcinoembryonic antigen (CEA) levels, T4 stage, poor differentiation, deficient DNA mismatch repair (dMMR), and vascular invasion, were correlated with deep-PNI. Multivariate analyses revealed that deep-PNI was associated with worse overall survival (OS; hazard ratio [HR], 3.546; 95% confidence interval [CI], 2.307-5.449; P < 0.001) and disease-free survival (DFS; HR, 2.921; 95% CI, 2.032-4.198; P < 0.001), compared with non-PNI. Conversely, no significant difference in OS or DFS was observed between the sup-PNI and non-PNI groups in multivariate analyses. The study demonstrated that the depth of PNI was an independent prognostic factor for patients with stage II colorectal cancer, and patients with deep PNI had a worse prognosis. Thus, patients with PNI require further subdivision according to the depth of invasion.

Stem-like CD8 T cells in stage I lung adenocarcinoma as a prognostic biomarker: A preliminary study.

This study aimed to investigate the presence of stem-like CD8 T (CD8 TSL) cells in lung adenocarcinoma (LUAD) and explore their relationships with the clinical outcomes. Multiplex immunofluorescence (mIF) was performed to identify CD8 TSL and antigen-presenting cells (APC) in 76 LUAD patients. Differences in the number of CD8 TSL cells based on tumor stage and the spatial relationships between CD8 TSL cells and APC niches were determined. The optimal cutoff value of CD8 TSL cells for predicting survival in patients with stage I LUAD was calculated. CD8 TSL cells were present in all tumors, and their numbers were significantly higher in stage I patients than in stage III patients (P = 0.010); CD8 TSL cells located in the APC niches accounted for 69.7% (53/76) of the hotspot fields. The optimal cutoff value for the number of CD8 TSL cells required to predict the overall survival (OS) in patients with stage I LUAD was 2.5 per 10000 μm2. The median OS and progression-free survival (PFS) in the high-level group (>2.5) were significantly (P < 0.001) longer than those in the low-level group (≤2.5). The number of CD8 TSL cells was an independent prognostic factor for stage I LUAD. Patients with more CD8 TSL cells had a lower risk of death and disease progression than those with less CD8 TSL cells. CD8 TSL cells were observed in patients with stages I-III LUAD and might serve as prognostic biomarkers for stage I LUAD.

Prognostic value of KRAS G12V mutation in lung adenocarcinoma stratified by stages and radiological features

ObjectiveKRAS G12V is one of the most common KRAS mutation variants in lung adenocarcinoma (LUAD), and yet its prognostic value is still unrevealed. In this study, we investigated the clinicopathologic characteristics and prognostic value of the KRAS G12V mutation in LUAD. MethodsData of 3829 patients who underwent LUAD resection between 2008 and 2020 were collected. Mutations were classified as wild-type, G12V, or non-G12V. The clinicopathologic characteristics, postoperative outcomes, and recurrence pattern were analyzed among groups. ResultsIn total, 3554 patients were wild-type and 275 patients harbored a KRAS mutation: 60 patients with G12V (22.2%) and 215 patients with non-G12V (77.8%). The KRAS G12V mutation was more frequent in male patients, older patients (≥60 years), former/current smokers, those patients with radiologic solid nodules, and those with highly invasive histologic subtypes. Tumors carrying KRAS G12V mutation exhibited elevated programmed death-ligand 1 expression in comparison with wild-type tumors. KRAS G12V was more prevalent in older patients and had less lymphovascular invasion compared with other mutation types. FGF3, RET, and KDR co-mutations occurred more frequently in the KRAS G12V group. Multivariate analysis demonstrated that the KRAS G12V mutation was an independent prognostic factor in stage Ⅰ tumors, whereas the KRAS non-G12V mutation was not. KRAS G12V was associated with early recurrence and locoregional recurrence. ConclusionsThe KRAS G12V mutation was associated with aggressive clinical-pathologic phenotype and early recurrence. To note, this mutation exhibited a significantly worse prognosis in patients with part-solid and stage Ⅰ lung adenocarcinoma. Meanwhile, the prognostic significance of KRAS G12C and G12V variants was comparable.

Siglec10 Expression on Tumor-associated Macrophages Is an Independent Prognostic Factor in Stage I Lung Adenocarcinoma.

Prognostic indicators for postoperative lung adenocarcinoma are elusive. The interaction between CD24 on tumor cells and sialic-acid-binding Ig-like lectin 10 (Siglec10) on tumor-associated macrophages (TAMs) is implicated in immune evasion in distinct tumors. However, the therapeutic significance of phagocytic checkpoints in lung adenocarcinoma remains unknown. We aimed to investigate the clinical relevance and prognostic significance of phagocytosis checkpoints mediated by Siglec10 in TAMs of patients with lung adenocarcinoma who underwent curative resection. In this single-center retrospective study, we analyzed the data of 423 patients with stage I lung adenocarcinoma resected between 1999 and 2016. Tissue microarrays were constructed, and CD24, CD68, and Siglec10 immunohistochemistry was performed. Additionally, we assessed the clinical significance and prognostic associations of these markers. CD24 expression was higher in the Siglec10-high expression group than that in the -low expression group. Multivariate analysis showed that combined high Siglec10 and CD24 expression was an independent predictor of recurrence-free probability. The combined high Siglec10 and CD68 expression was a significant independent predictor of overall survival. Univariate analysis demonstrated that the 5-year probability of post-recurrence survival of patients with combined high Siglec10 and CD68 expression was lower than that of the other patients. High TAM Siglec10 expression and tumor CD24 expression are correlated, and the high Siglec10+CD24 combination is a major risk factor for recurrence. CD68+Siglec10 TAMs are important prognostic factors. Siglec10 expression on TAMs is essential for tumor microenvironment immunoregulation and offers a promising new immunotherapeutic approach for lung adenocarcinoma.

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

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

Lymphovascular invasion and p16 expression are independent prognostic factors in stage I vulvar squamous cell carcinoma

The objective of this study was to identify clinicopathologic parameters associated with disease outcome in FIGO stage I vulvar squamous cell carcinoma (vSqCC). The cohort consisted of 126 patients diagnosed with vSqCC in the period 2006–2016 who underwent primary vulvar surgery and evaluation of groin lymph node status. Tumors were reviewed by an experienced gynecologic pathologist. p16 and p53 protein expression by immunohistochemistry and HPV status were analyzed in 116 tumors. Clinicopathologic parameters, protein expression and HPV status were analyzed for association with progression-free and overall survival (PFS, OS). p16 expression and aberrant p53 were found in 49 (42%) and 61 (53%) tumors, respectively. Sixty-six tumors were HPV-associated (57%). Relapse was diagnosed in 35/126 (28%) of patients, and 23 (18%) died of disease. Tumor diameter > 4 cm (p = 0.013), lymphovascular space invasion (LVSI; p < 0.001), the presence of lichen sclerosus (p = 0.019), p16 expression (p = 0.007), p53 expression (p = 0.012), HPV status (p = 0.021), lymph node metastasis (p < 0.001) and post-operative radiotherapy (p < 0.001) were significantly related to OS in univariate analysis. Tumor diameter > 4 cm (p = 0.038), LVSI (p = 0.003), the presence of lichen sclerosus (p = 0.004), p16 expression (p = 0.004), HPV status (p = 0.039), lymph node metastasis (p < 0.001) and post-operative treatment (p < 0.001), were significantly related to PFS in univariate analysis. Age, BMI and surgical resection involvement were not significantly associated with OS or PFS. In multivariate Cox analysis, LVSI and p16 expression were independent prognosticators of OS (p < 0.001 and p = 0.02, respectively) and PFS (p = 0.018, p = 0.037). In conclusion, LVSI and p16 expression are independent prognostic factors in stage I vSqCC.

Lymphovascular invasion and p16 expression are independent prognostic factors in stage I vulvar squamous cell carcinoma (1129)

Lymphovascular invasion and p16 expression are independent prognostic factors in stage I vulvar squamous cell carcinoma (1129)

Prognosis analysis of radical or modified radical hysterectomy and simple hysterectomy in patients with stage Ⅱ endometrial cancer

Objective: To compare the prognosis and perioperative situation of patients with stage Ⅱ endometrial cancer (EC) between radical hysterectomy/modified radical hysterectomy (RH/mRH) and simple hysterectomy (SH). Methods: A total of 47 patients diagnosed EC with stage Ⅱ [International Federation of Gynecology and Obstetrics (FIGO) 2009] by postoperative pathology, from January 2006 to January 2021 in Peking University People's Hospital, were analyzed retrospectively. The patients were (54.4±10.7) years old, and the median follow-up time was 65 months (ranged 9-138 months). They were divided into RH/mRH group (n=14) and SH group (n=33) according to the scope of operation. Then the prognosis of patients between the groups were compared, and the independent prognostic factors of stage Ⅱ EC were explored. Results: (1) The proportions of patients with hypertension in RH/mRH group and SH group were 2/14 and 45% (15/33), the amounts of intraoperative blood loss were (702±392) and (438±298) ml, and the incidence of postoperative complications were 7/14 and 15% (5/33), respectively. There were significant differences (all P<0.05). (2) The median follow-up time of RH/mRH group and SH group were 72 vs 62 months, respectively (P=0.515). According to Kaplan-Meier analysis and log-rank method, the results showed that there were no significant difference in 5-year progression-free survival (PFS) rate (94.3% vs 84.0%; P=0.501), and 5-year overall survival rate (92.3% vs 92.9%; P=0.957) between the two groups. Cox survival analysis indicated that age, pathological type, serum cancer antigen 125 (CA125), and estrogen receptor (ER) status were associated with 5-year PFS rate (all P<0.05). But the scope of hysterectomy (RH/mRH and SH) did not affect the 5-year PFS rate of stage Ⅱ EC patients (P=0.508). And level of serum CA125 and ER status were independent prognostic factors for 5-year PFS rate (all P<0.05). Conclusions: This study could not find any survival benefit from RH/mRH for stage Ⅱ EC, but increases the incidence of postoperative complications. Therefore, the necessity of extending the scope of hysterectomy is questionable.

Prognostic value of KRAS G12C mutation in lung adenocarcinoma stratified by stages and radiological features

ObjectivesThe role of KRAS G12C is of particular interest given the promising clinical activity of KRAS G12C-specific inhibitors. This study comprehensively investigated the clinicopathological characteristics and prognostic value of KRAS G12C mutation in patients with surgically resected lung adenocarcinoma. MethodsData were collected on 3828 patients with completely resected primary lung adenocarcinomas who underwent KRAS mutation analysis between 2008 and 2020. The association between KRAS G12C and clinicopathologic characteristics, molecular profiles, recurrence patterns, and postoperative outcome were explored. ResultsTwo hundred seventy-five patients (7.2%) were confirmed to harbor a KRAS mutation, of whom 83 (30.2%) had the G12C subtype. KRAS G12C was more frequent in men, former/current smokers, radiologic solid nodules, invasive mucinous adenocarcinoma, and solid predominant tumors. KRAS G12C tumors had more lymphovascular invasion and higher programmed death-ligand 1 expression than KRAS wild-type tumors. TP53 (36.8%), STK11 (26.3%), and RET (18.4%) mutations were the 3 most frequent in the KRAS G12C group. Logistic regression analysis showed patients with KRAS G12C mutation were prone to experience early recurrence and locoregional recurrence. KRAS G12C mutation was found to be significantly associated with poor survival after propensity score matching. Stratified analysis showed that the KRAS G12C was an independent prognostic factor in stage I tumors and part-solid lesions, respectively. ConclusionsThe KRAS G12C mutation had a significant prognostic value in stage I lung adenocarcinomas as well as in part-solid tumors. Furthermore, it exhibited a potentially aggressive phenotype associated with early and locoregional recurrence. These findings might be relevant as better KRAS treatments are developed for clinical application.

Clinical Analysis and Prognostic Prediction Model for Patients with Uterine Leiomyosarcoma at FIGO Stage I.

To reveal the clinical status and construct a predictive prognostic model for patients with uterine leiomyosarcoma (uLMS) at International Federation of Gynecology and Obstetrics (FIGO) stage I. The medical records of patients with stage I uLMS during the study period were retrospectively reviewed. Multiple imputation, Martingale residuals and restricted cubic spline were used for data processing. Univariate and multivariate analyses were used to determine independent prognostic factors. The Schoenfeld individual test was used to verify the proportional hazards (PH) assumption. The predictive ability of the nomogram was validated internally. Ultimately, 102 patients were included. The median age at diagnosis was 51 years old. During the medium follow-up time of 68 months, 55 (53.9%) patients developed recurrence. The median recurrence interval was 32 months. The most common metastatic site was the lung (27 cases). Eventually, 38 (37.3%) patients died of uLMS. The 3-year and 5-year overall survival rates were 66.0% and 52.0%, respectively. Age at diagnosis >49 years, larger tumor size, MI>10/10HPF, presence of LVSI and Ki-67 labeling index (LI) >25% (P=0.0467, 0.0077, 0.0475, 0.0294, and 0.0427, respectively) were independent prognostic factors. The PH assumption remained inviolate. The concordance index was 0.847, the area under the time-dependent receiver operating characteristic curve surpassed 0.7, and the calibration curve showed gratifying consistency. Age at diagnosis, tumor size, MI, LVSI, and Ki-67 LI were identified as independent prognostic factors for stage I uLMS. This prognostic nomogram would provide personalized assessment with superior predictive performance.

A Novel Systematic Oxidative Stress Score Predicts the Survival of Patients with Early-Stage Lung Adenocarcinoma

This study aimed to construct an effective nomogram based on the clinical and oxidative stress-related characteristics to predict the prognosis of stage I lung adenocarcinoma (LUAD). A retrospective study was performed on 955 eligible patients with stage I LUAD after surgery at our hospital. The relationship between systematic-oxidative-stress biomarkers and the prognosis was analyzed. The systematic oxidative stress score (SOS) was established based on three biochemical indicators, including serum creatinine (CRE), lactate dehydrogenase (LDH), and uric acid (UA). SOS was an independent prognostic factor for stage I LUADs, and the nomogram based on SOS and clinical characteristics could accurately predict the prognosis of these patients. The nomogram had a high concordance index (C-index) (0.684, 95% CI, 0.656-0.712), and the calibration curves for recurrence-free survival (RFS) probabilities showed a strong agreement between the nomogram prediction and actual observation. Additionally, the patients were divided into two groups according to the cut-off value of risk points based on the nomogram, and a significant difference in RFS was observed between the high-risk and low-risk groups (p < 0.0001). SOS is an independent prognostic indicator for stage I LUAD. These things considered, the constructed nomogram based on SOS could accurately predict the survival of those patients.

A High-Quality Nomogram for Predicting Lung Metastasis in Newly Diagnosed Stage IV Thyroid Cancer: A Population-Based Study.

Introduction: Lung metastasis (LM) implies a very dismal event in patients with thyroid cancer. We aimed to construct a nomogram to predict LM for newly diagnosed stage IV thyroid cancer. Methods: A total of 1407 stage IV thyroid cancer patients were gathered from the surveillance, epidemiology, and end results (SEER) database. Pearson's Chi-squared test or Fisher's exact test was used to identify LM-related factors, and logistic regression analysis was employed to identify independent risk parameters of LM, which were included to establish a nomogram model by R software. The discriminative ability and predictive accuracy of the nomogram were assessed using the area under the curve (AUC) and calibration plots. Cox regression analysis and Kaplan-Meier analysis were applied to evaluate the clinical utility of this model. A simulation trial was conducted to verify the health economic value of this nomogram in predicting TCLM. Results: Five variables were found to be independent risk predictors of LM, including grade, histology, N stage, bone metastasis, and liver metastasis. The results of the AUC and calibration curves demonstrated that the nomogram exhibited outstanding performance for predicting the risk of LM patients both internally and externally. The LM prediction risk was an independent prognostic factor for stage IV thyroid cancer patients [P = .009, hazard ratio (HR): 1.812, 95% CI: 1.163-2.824]. Conclusion: We successfully developed a predictive model for stage IV thyroid cancer, which provides important information for identifying patients at high risk of LM and implementing early preventive interventions to improve their outcomes.

A novel prognostic model to predict OS and DFS of stage II/III gastric adenocarcinoma patients in China

BackgroundThe prognosis of advanced gastric adenocarcinoma (GAC) after radical gastrectomy varies greatly. We aimed to build and validate a novel individualized nomogram based on inflammation index and tumor markers for patients with stage II/III GAC. MethodsA total of 755 individuals with stage II/III GAC who had undergone radical gastrectomy at the First Affiliated Hospital of Zhengzhou University between 2012 and 2017 were included in this retrospective study. The patients were randomly divided into a training cohort (n ​= ​503) and a validation cohort (n ​= ​252). Univariate and multivariate analyses were used to determine independent prognostic factors of overall survival (OS) and disease-free survival (DFS). A nomogram was developed based on these independent factors. The concordance index (C-index) and calibration curves were used to evaluate the predictive accuracy of the nomogram. ResultsUnivariate and multivariate analyses demonstrated that older age, poor differentiation, advanced stage, elevated neutrophil-to-lymphocyte ratio (NLR), lower hemoglobin, and high carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were significantly associated with lower OS and DFS and were independent prognostic factors in stage II/III GAC. The nomogram developed based on these factors in the training cohort showed excellent calibration and discrimination (OS: C-index ​= ​0.739, 95% CI ​= ​0.706–0.772; DFS: C-index ​= ​0.735, 95% CI ​= ​0.702–0.769). In the internal validation cohort, the nomogram was also well-calibrated for the prediction of OS and DFS; it was superior to the 8th edition UICC/AJCC TNM staging system (for OS: C-index ​= ​0.746 vs. 0.679, respectively; for DFS: C-index ​= ​0.736 vs. 0.675, respectively; P ​< ​0.001). ConclusionThe nomogram model could reliably predict OS and DFS in stage II/III gastric cancer patients with radical gastrectomy. It may help physicians make better treatment decisions.

GYNECOLOGICAL MALIGNANCIES

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)

Preoperative CRP(-)/CEA(-)/CA19-9(-)/non-T4 in Stage III Colorectal Cancer Is Favorable Risk for Recurrence.

We evaluated the prognostic impact of a novel C-reactive protein (CRP) cut-off value (0.6 mg/dl) and carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9) in stage II/III colorectal cancer. Four hundred ninety-eight patients with stage II (n = 275) or stage III (n = 223) colorectal cancer, surgically treated between January 2010 and December 2016, were analyzed. The optimal CRP cut-off value was fixed at 0.6 mg/dl to predict recurrence based on the receiver operating characteristic curve. Prognostic factors, including CRP/CEA/CA19-9 status, for relapse-free survival (RFS) were evaluated by multivariate analysis. Recurrent rates were 15% and 32% in stages II and III, respectively. In stage II, CRP, CEA, and CA19-9 were not significant prognostic factors for RFS. In stage III, the RFS of the low CRP group was significantly better than that of the high CRP group (p = 0.002). In stage III, the RFS of CRP(-)/CEA(-) or CRP(-)/CA19-9(-) was significantly better than the other group, as opposed to the RFS of the CEA(-)/CA19-9(-) group that was not. The CRP(-)/CEA(-)/CA19-9(-) group recurrence rate in stage III was significantly better than the CRP(+)/CEA(-)/CA19-9(-) group (20% vs. 50%, p = 0.006). Multivariate analysis revealed that CRP(-)/CEA(-)/CA19-9(-) (p = 0.04) and non-T4 (p < 0.001) were good independent prognostic factors in stage III. The CRP(-)/CEA(-)/CA19-9(-)/non-T4 group recurrence rate in stage III was 11% (8 out of 73). In stage III, the CRP(-)/CEA(-)/CA19-9(-)/non-T4 group is favorable risk for recurrence.

Clinical predictors of survival in real world practice in stage IV melanoma.

While studies continually identify new clinical prognostic factors in stage IV melanoma, the introduction of targeted and immunotherapies have revolutionised the prognosis of advanced melanoma since 2011. The study aims to investigate the prognostic significance of past and newly identified clinical factors in a contemporary cohort. A retrospective analysis of The Canberra Hospital melanoma database identified 161 patients with Stage IV melanoma between 2011 and 2017. Survival was analysed by demographics and clinical factors with chi-square tests to determine significance. Logistic binary regression was performed to test the independence of the clinical factors on predicting the survival outcome. Overall, the 3-month, 6-month, 9-month, and 12-month stage IV melanoma survival rate of our cohort was 79%, 67%, 55%, and 45%, respectively. Age, sex, and BRAF mutation status were found to have no impact on survival, whereas M1d category of the American Joint Committee on Cancer (AJCC) staging (8th edition), neutrophil-lymphocyte ratio (NLR) >3, elevated serum LDH, more than three metastatic sites, brain metastases, poorer Eastern cooperative oncology group (ECOG) status were associated with poorer survival. Binary logistic regression test identified AJCC staging, NLR (cutoff score 3), LDH, and brain metastases as independent prognostic factors. Most clinical factors investigated in this study were found to have a statistically significant impact on survival, with AJCC (8th edition) staging M1a-M1d, NLR (cutoff score 3), LDH, and brain metastases identified as independent prognostic factors in stage IV melanoma from a contemporary cohort treated with targeted therapies and immunotherapies.

CILP, a Putative Gene Associated With Immune Infiltration in Breast Cancer Brain Metastases.

Breast cancer (BC) is the second leading cause of brain metastases (BM), with high morbidity and mortality. The aim of our study was to explore the effect of the cartilage intermediate layer protein (CILP) on breast cancer brain metastases (BCBM). Using a weighted gene coexpression network analysis (WGCNA) in GSE100534 and GSE125989 datasets, we found that the yellow module was closely related to the occurrence of BCBM, and CILP was a hub gene in the yellow module. Low CILP expression was associated with a poor prognosis, and it was an independent prognostic factor for stage III–IV BC determined using Cox regression analysis. A nomogram model including CILP expression was established to predict the 5-, 7-, and 10-year overall survival (OS) probabilities of stage III–IV BC patients. We found that CILP mRNA expression was downregulated in BCBM through GSE100534, GSE125989, and GSE43837 datasets. In addition, we found that CILP mRNA expression was negatively correlated with vascular endothelial growth factor A (VEGFA), which is involved in regulating the development of BM. UALCAN analysis showed that CILP expression was downregulated in HER2-positive (HER2+) and triple-negative breast cancer (TNBC), which are more prone to BM. The vitro experiments demonstrated that CILP significantly inhibited BC cell proliferation and metastasis. Western blot (WB) results further showed that the mesenchymal protein marker vimentin was significantly downregulated following CILP overexpression, suggesting that CILP could participate in migration through epithelial–mesenchymal transition (EMT). A comparison of CILP expression using immunohistochemistry in BC and BCBM showed that CILP was significantly downregulated in BCBM. In addition, gene set variation analysis (GSVA) revealed that CILP was associated with the T-cell receptor signaling pathway in BCBM and BC, indicating that CILP may be involved in BCBM through immune effects. BCBM showed lower immune infiltration than BC. Moreover, CILP expression was positively correlated with HLA-II, T helper cells (CD4+ T cells), and Type II IFN Response in BCBM. Collectively, our study indicates that CILP is associated with immune infiltration and may be a putative gene involved in BCBM. CILP offers new insights into the pathogenesis of BCBM, which will facilitate the development of novel targets for BCBM patients.

Tumor Size Is an Independent Prognostic Factor for Stage I Ovarian Clear Cell Carcinoma: A Large Retrospective Cohort Study of 1,000 Patients.

ObjectiveThe aim of this study was to investigate the prognostic value and stratification cutoff point for tumor size in stage I ovarian clear cell carcinoma (OCCC).MethodsThis was a retrospective cohort study using the Surveillance, Epidemiology, and End Results database (version: SEER 8.3.9). Patients diagnosed with stage I OCCC from 1988 to 2018 were included for further analysis. X-Tile software was used to identify the potential cutoff point for tumor size. Stratification analysis, propensity score matching, and inverse probability weighting analysis were used to balance the potential confounding factors.ResultsA total of 1,000 stage I OCCC patients were included. Of these 1,000 patients, median follow-up was 106 months (95% confidence interval [CI]: 89–112 months). Multivariate analysis showed that tumor size, age at diagnosis, and stage IC were significantly associated with stage I OCCC patients. Eight centimeters is a promising cutoff point that can divide stage I OCCC patients into a good or a poor prognosis group. After controlling potential confounding factors with propensity score matching and inverse probability weighting, we demonstrated that stage I OCCC patients with tumor size ≤ 8 cm enjoyed a significantly better 5-year overall survival (OS, 89.8% vs. 81%, p < 0.0001). Tumor size ≤ 8 cm was an independent prognostic factor of stage I OCCC patients (hazard ratio [HR] 0.5608, 95% CI: 0.4126–0.7622, p = 0.0002).ConclusionsTumor size is an independent prognostic factor for stage I OCCC, and 8 cm is a promising cutoff point for tumor size for risk stratification. However, using tumor size in the stratification management of stage I OCCC patients warrants further investigation.

Cyclin D1 Serves as a Poor Prognostic Biomarker in Stage I Gastric Cancer.

TNM stage still serves as the best prognostic marker in gastric cancer (GC). The next step is to find prognostic biomarkers that detect subgroups with different prognoses in the same TNM stage. In this study, the expression levels of epidermal growth factor receptor (EGFR) and cyclin D1 were assessed in 96 tissue samples, including non-tumorous tissue, adenoma, and carcinoma. Then, the prognostic impact of EGFR and cyclin D1 was retrospectively investigated in 316 patients who underwent R0 resection for GC. EGFR positivity increased as gastric tissue became malignant, and cyclin D1 positivity was increased in all the tumorous tissues. However, there was no survival difference caused by the EGFR positivity, while the cyclin D1-postive group had worse overall survival (OS) than the cyclin D1-negative group in stage I GC (10-year survival rate (10-YSR): 62.8% vs. 86.5%, p = 0.010). In subgroup analyses for the propensity score-matched (PSM) cohort, there were also significant differences in the OS according to the cyclin D1 positivity in stage I GC but not in stage II and III GC. Upon multivariate analysis, cyclin D1 positivity was an independent prognostic factor in stage I GC. In conclusion, cyclin D1 may be a useful biomarker for predicting prognosis in stage I GC.

Tumor budding is an independent prognostic factor in stage III colon cancer patients: a post-hoc analysis of the IDEA-France phase III trial (PRODIGE-GERCOR)

Histological characteristics at the invasive front may reflect tumor aggressiveness; specifically, tumor budding (Bd) is an emerging prognostic biomarker in colon cancer (CC). We explored further the significance of Bd for risk stratification by evaluating survival of stage III CC patients included in the IDEA-France phase III trial.This post-hoc study was conducted on tissue slides from 1048 stage III CC patients. Bd was scored by central review by the Bd criteria of the 2016 International Tumor Budding Consensus Conference (ITBCC 2016) and classified as Bd1 (0-4 buds/0.785 mm2), Bd2 (5-9 buds), and Bd3 (≥10 buds) categories. Disease-free survival (DFS) and overall survival (OS) were analyzed by the log-rank test. Clinicopathological features and Immunoscore® were correlated with Bd.Overall, Bd1, Bd2, and Bd3 were observed in 39%, 28%, and 33% of CC, respectively. Bd2 and Bd3 were associated with vascular (P = 0.002) and perineural invasions (P = 0.0009). The 3-year DFS and the 5-year OS rates for Bd (1 versus 2-3) were 79.4% versus 67.2% (P = 0.001) and 89.2% versus 80.8% (P = 0.001), respectively. This was confirmed after adjustment for relevant clinicopathological features for DFS [hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.12-1.77, P = 0.003] and OS (HR 1.65, 95% CI 1.22-2.22, P = 0.001). When combined with pTN stage and Immunoscore® subgroups, Bd significantly improved disease prognostication.Bd demonstrated its independent prognostic value for DFS and OS. Given these findings, Bd as per the ITBCC 2016 should be mandatory in every pathology report in stage III CC patients. Bd and Immunoscore® could play a complementary role in personalized health care in this setting.