Worse 5-year Cancer-specific Survival Research Articles

The Expression of Alamandine Receptor MrgD in Clear Cell Renal Cell Carcinoma Is Associated with a Worse Prognosis and Unfavorable Response to Antiangiogenic Therapy.

Renal cell carcinoma (RCC) ranks among the most prevalent malignancies in Western countries, marked by its notable heterogeneity, which contributes to an unpredictable clinical trajectory. The insufficiency of dependable biomarkers adds complexity to assessing this tumor progression. Imbalances of several components of the intrarenal renin-angiotensin system (iRAS) significantly impact patient prognoses and responses to first-line immunotherapies. In this study, we analyzed the immunohistochemical expression of the Mas-related G-protein-coupled receptor D (MrgD), which recognizes the novel RAS peptide alamandine (ALA), in a series of 87 clear cell renal cell (CCRCCs), 19 papillary (PRCC), 7 chromophobe (ChRCC) renal cell carcinomas, and 11 renal oncocytomas (RO). MrgD was expressed in all the renal tumor subtypes, with a higher mean staining intensity in the PRCCs, ChRCCs, and ROs. A high expression of MrgD at the tumor center and at the infiltrative front of CCRCC tissues was significantly associated with a high histological grade, large tumor diameter, local invasion, and locoregional node and distant metastasis. Patients with worse 5-year cancer-specific survival and a poorer response to antiangiogenic tyrosine-kinase inhibitors (TKIs) showed higher MrgD expression at the center of their primary tumors. These findings suggest a possible role of MrgD in renal carcinogenetic processes. Further studies are necessary to unveil its potential as a novel biomarker for CCRCC prognosis and response to frontline therapies.

Hypomagnesemia and Survival in Patients with Cervical Cancer Treated with Definitive Chemoradiotherapy

Hypomagnesemia is a common side effect of platinum-based chemotherapy regimens. Although there are data reporting that hypomagnesemia is associated with worse survival in patients receiving platinum-based chemotherapy or chemoradiotherapy (CRT), this has not been documented in patients with cervical cancer treated with definitive CRT. We hypothesized that in patients with cervical cancer undergoing definitive CRT, on-treatment hypomagnesemia would be associated with longer treatment duration and worse cancer-specific survival (CSS). Patients with cervical cancer treated with definitive CRT from 1999 to 2015 were identified from a single cancer center's clinicopathologic database. Lowest on-treatment magnesium value was recorded and categorized as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grading (grade 1: <0.7 - 0.5 mmol/L, grade 2: <0.5 - 0.4 mmol/L, grade 3: <0.4-0.3 mmol/L, and grade 4 <0.3 mmol/L). Grade 0 was defined as ≥ 0.7 mmol/L. Treatment duration was defined as the number of days between the first day of radiotherapy until the last day of pelvic treatment (either brachytherapy or pelvic external beam radiotherapy boost). Prolonged treatment was considered as any treatment duration greater than 63 days. CSS for patients with either grade 0-1 or grade ≥ 2 CTCAE v5.0 magnesium toxicity was estimated using the Kaplan-Meier method, and the Peto & Peto modification to the generalized Gehan-Wilcoxon was used to determine statistical significance between groups. Associations with prolonged treatment duration was explored using logistic regression. P-values of <0.05 were considered statistically significant. A total of 186 patients were identified; median follow-up was 7 (IQR 2-11) years. 125 (67%) had stage I-II disease and 61 (33%) stage III-IV. Median treatment duration was 51 (IQR 48-57) days. All patients received concurrent weekly cisplatin-based chemotherapy with RT: the majority (n = 133; 72%) received 5 or 6 cycles. 147 (79%) patients received routine IV magnesium infusion with their chemotherapy and 173 (93%) received routine IV mannitol. During treatment the highest CTCAE v5.0 magnesium toxicity score was grade 0-1 in 158 (85%) and grade ≥ 2 in 28 (15%). Magnesium grade ≥ 2 was associated with worse 5-year CSS [grade 0-1: 5yr CSS 67.2%, (95% CI 60.1-75.1); grade ≥ 2: 5yr CSS 50%, (95% CI 34.5-72.4); p = 0.039]. Magnesium status was not associated with an increase in treatment duration [OR 1.465 (95% CI 0.3177 - 6.753); p = 0.625]. On-treatment hypomagnesemia ≥ grade 2 (CTCAE v5.0) was associated with worse CSS but did not predict longer treatment duration. This is the first study that shows a detrimental survival impact of on-treatment hypomagnesemia in this patient population. These findings highlight the need to ensure adequate monitoring, support and correction of magnesium during definitive CRT.

The use of the second thoracic vertebral landmark for skeletal muscle assessment and computed tomography-defined sarcopenia evaluation in patients with head and neck cancer.

The cross-sectional area (CSA) of skeletal muscle (SM) at the third lumbar vertebra (L3) is used to determine computed tomography (CT)-defined sarcopenia. We investigated the feasibility of SM assessment at the second thoracic vertebra (T2) in patients with head and neck cancer (HNC). Diagnostic PET-CT scans were used to develop a prediction model for L3-CSA using T2-CSA. Effectiveness of the model and cancer-specific survival (CSS) were investigated. Scans of 111 patients (85% male) were evaluated. The predictive formula: L3-CSA (cm2 )=174.15 + [0.212 × T2-CSA (cm2 )] - [40.032 × sex] - [0.928 × age (years)] + [0.285 × weight (kg)] had good correlation r= 0.796, ICC=0.882 (p< 0.001). SM index (SMI) mean difference (bias) was -3.6% (SD 10.2, 95% CI -8.7% to 1.3%). Sensitivity (82.8%), specificity (78.2%), with moderate agreement (ƙ= 0.540, p< 0.001). Worse 5-year CSS with lower quartile T2-SMI (51%, p= 0.003). SM at T2 can be effectively used for CT-defined sarcopenia evaluation in HNC.

Prognostic value of the sarcomatoid component in bladder cancer: A propensity score matching study.

Sarcomatoid carcinoma of the bladder is rare, and little is known about the prognostic impact of the proportion of sarcomatoid components of the bladder. The present study aimed to assess the prognostic value of the proportion of sarcomatoid components with regard to death and recurrence rates in patients with bladder cancer (BC), and to validate the worse survival results of sarcomatoid carcinomas of the bladder using propensity score matching. Patients with sarcomatoid carcinoma of the bladder who were treated at the Affiliated Hospital of Qingdao University between August 2010 and May 2021 were included in the study. A 1:2 propensity score matching system based on age, sex and pathological T stage was used for sarcomatoid and non-sarcomatoid carcinoma matching. Finally, 114 patients with BC were included. Patients with sarcomatoid carcinoma had worse 5-year cancer-specific survival (CSS) (69.1 vs. 86.9%; log-rank P=0.008) and recurrence-free survival (RFS) (64.1 vs. 83.6%; log-rank P=0.001) rates compared with patients with non-sarcomatoid carcinoma, as had the subgroup with muscle invasion. Multivariate analysis revealed sarcomatoid carcinoma as an independent prognostic factor. Patients with a low proportion of sarcomatoid components (1-50%) had a better prognosis than patients with a high proportion (>50%), and no significant difference was found compared with the non-sarcomatoid group. Overall, a proportion of sarcomatoid components >50% was a predictor of CSS and RFS. Sarcomatoid components markedly increased the risk of death and recurrence in muscle-invasive BC, but not in non-muscle-invasive BC. A higher proportion of sarcomatoid components was significantly associated with poorer survival.

Altered Tissue and Plasma Levels of Fibroblast Activation Protein-α (FAP) in Renal Tumours.

Simple SummaryMalignant epithelial tumour’s behaviour in the kidney has traditionally been analysed attending to different prognostic parameters focussed on the proliferating neoplastic cell. This is the case of renal cell carcinoma (RCC), in which a large tumour diameter, high histological grade, and the presence of necrosis, among other factors, have been related with a high risk of distant metastasis and, therefore, worse survival. Recently, several elements of the tumour microenviroment, such as cancer-associated fibroblasts (CAFs), are being studied in order to develop more accurate diagnostic and therapeutic approaches. We present data that support that the fibroblast activation protein-α (FAP), a CAF biomarker, provides interesting information both in tumour tissues and in plasma from patients with RCC. (1) Background: Renal cell carcinoma (RCC) is a heterogeneous and complex disease with only partial response to therapy, high incidence of metastasis and recurrences, and scarce reliable biomarkers indicative of progression and survival. Cancer-associated fibroblasts (CAFs) play an important role supporting and promoting renal cancer progression. (2) Methods: In this study, we analysed fibroblast activation protein-α (FAP) immunohistochemical expression and its soluble isoform (sFAP) in tumour tissues and plasma from 128 patients with renal tumours. (3) Results: FAP is expressed in the cell surface of CAFs of the tumour centre and infiltrating front from clear cell renal cell carcinomas (CCRCC, n = 89), papillary renal cell carcinomas (PRCC, n = 21), and chromophobe renal cell carcinomas (ChRCC, n = 8), but not in the benign tumour renal oncocytoma (RO, n = 10). A high expression of FAP and low levels sFAP are significantly associated with high tumour diameter, high grade, and high pT stage, lymph node invasion, development of early metastases, and worse 5-year cancer specific survival of CCRCC patients. (4) Conclusions: These findings corroborate the potential usefulness of FAP immunohistochemistry and plasma sFAP as a biomarker of CCRCC progression and point to CAF-related proteins as promising immunohistochemical biomarkers for the differential diagnosis of ChRCC and RO.

Enlarged Mediastinal Lymph Nodes in Computed Tomography are a Valuable Prognostic Factor in Non-Small Cell Lung Cancer Patients with Pathologically Negative Lymph Nodes.

BackgroundMost non-small cell lung cancer patients with enlarged mediastinal lymph nodes (LN) in preoperative computer tomography (CT) images are diagnosed with N0 in the pathological examination after surgery. However, these patients seem to have worse survival than those without enlarged mediastinal LN in our clinical practice. This study aimed to investigate whether the size of mediastinal LN is correlated with the prognosis in pathological N0 patients, which could help us to predict the prognoses further.MethodsThe retrospective cohort study involved 758 N0 patients with a thin layer CT scan. We have measured the size of mediastinal LN, including long diameter, short diameter, and volume on CT image, and classified patients by X-tile. Next, we explored the risk factors of enlarged LN by univariate and multivariate logistic analysis. Then, we have compared the 5-year cancer-specific survival by Kaplan–Meier and log-rank method. Multivariate Cox analysis was utilized to further survival analysis. Finally, we have constructed the prediction model by nomogram.ResultsA total of 150 N0 patients (19.8%) had mediastinal LN enlargement in our study. After multivariate logistic analysis, we found the LN enlargement was significantly correlated with age (p=0.001), pathology (p < 0.001) and tumor recurrence (p < 0.001). The patients with LN enlargement had a worse 5-year cancer-specific survival (75.3% vs 92.8%, p < 0.001) after Kaplan–Meier analysis. Patients with a larger volume had increased risk of tumor-associated death when compared with the normal group (p < 0.001) by multivariate Cox analyses.ConclusionN0 patients with larger mediastinal LN had a worse 5-year cancer-specific survival and a higher risk of recurrence. The volume of LN was the most valuable prognostic factor in N0 patients.

Preoperative squamous cell carcinoma antigen and albumin serum levels predict the survival of patients with stage T1-3N0M0 esophageal squamous cell carcinoma: a retrospective observational study

BackgroundThis study aimed to explore the significance of preoperative levels of squamous cell carcinoma antigen (SCC-Ag) and albumin on the cancer-specific survival (CSS) of patients with stage T1-3N0M0 in esophageal squamous cell cancer (ESCC).MethodsThe data of 308 patients who underwent esophagectomy between 1996 and 2011 were analyzed. SCC-Ag and albumin levels were measure 1 week before surgery. The optimal cutoff levels of SCC-Ag and albumin were determined using the X-Tile software, which were 1.0 μg/L and 39.8 g/L, respectively. The associations between SCC-Ag and albumin levels and clinicopathological characteristics were assessed using the χ2 test, Student’s t-test and Fisher’s exact test. Cox univariable and multivariable analyses were computed to identify SCC-Ag and albumin levels as independent prognostic factors related to the CSS of patients with ESCC. We used the Kaplan-Meier survival curve to determine the significance of SCC-Ag and albumin level on ESCC in the long-term follow-up.ResultsThe 5-year CSS rate for the entire cohort was 65.0%. There was a significant difference in CSS between the low and high SCC-Ag level groups (hazard ratio [HR], 1.828, 95% confidence interval [CI], 1.203–2.778; P = 0.005). Patients with ESCC with low albumin level had a worse CSS than those with high albumin level (HR, 0.540; 95% CI, 0.348–0.838; P = 0.006). Patients with both high SCC-Ag and low albumin levels had worse 5-year CSS than patients with low SCC-Ag and high albumin levels (P < 0.05).ConclusionsPreoperative serum SCC-Ag and albumin levels can predict survival in patients ESCC with stage T1-3N0M0. Patients with ESCC with high SCC-Ag and low albumin levels may have a poor survival outcome.

Tumour infiltrating lymphocyte expression of PD-1 as a favourable prognostic factor in patients with mismatch repair competent colorectal cancer.

631 Background: Immune checkpoint activation is recognised in mismatch repair (MMR) deficient colorectal cancer (CRC), and Programmed Cell Death Protein-1 (PD-1) inhibitors have been shown to have therapeutic benefit in this patient group. However, the role of PD-1 and PD Ligand-1 (PDL-1) in patients with MMR competent CRC remains unclear. The present study examined the relationship between tumor infiltrating lymphocyte (TIL) PD-1 and tumour PDL-1 expression, tumour microenvironment (TME) characteristics and cancer-specific survival (CSS) of patients with MMR competent CRC. Methods: The presence of TIL PD-1 and tumour cell PDL-1 expression was examined in patients who had undergone resection of TNM I-III CRC using a tissue microarray. Relationship with clinicopathological characteristics and the TME (Klintrup-Makinen (KM) grade, Immunoscore, tumour stroma percentage (TSP) and Glasgow Microenvironment Score (GMS)) and CSS was examined. Results: 189 patients were included; 64% were older than 65 and 52% were male. PDL-1 expression was not associated with clinicopathological or TME characteristics. Lymphocyte PD-1 expression was not associated with clinicopathological characteristics, but was associated with a high KM grade ( P&lt; 0.001), high Immunoscore ( P&lt; 0.001), low TSP ( P= 0.068) and a low GMS ( P&lt; 0.001). On multivariate survival analysis, high TIL PD-1 expression was associated with improved CSS (HR 0.60, P= 0.016) independent of Immunoscore (HR 0.74, P= 0.03) and TSP (HR 1.91, P= 0.027). PDL1 expression was not associated with CSS on univariate or multivariate analysis. Pre-operative aspirin use was known for 131 patients. Aspirin use showed a trend towards improved 5-year CSS in patients with low PDL-1 expression (100% vs. 77%, P= 0.103) but worse 5-year CSS in those with high expression (55% vs. 82%, P= 0.045). Conclusions: The presence of PD-1 expressing TILs is a favourable prognostic factor in MMR competent CRC independent of other TME characteristics. Furthermore, the relationship between aspirin and CSS may be dependent on PDL-1 expression. Both PD-1 and PDL-1 may be potential prognostic and predictive markers in patients with MMR competent CRC.

Behavior of breast cancer in young women: A Surveillance Epidemiology and End Results (SEER) database review.

6 Background: Advanced age is a major risk factor for breast cancer in women. Small sized studies have reported variable outcome of breast cancer in young women. Our study was done to evaluate tumor characteristic and cancer specific survival among young women. Methods: The 1973-2009 SEER database was reviewed for women with breast cancer diagnosed between 2004 and 2009. Patients were grouped by age into: A (≤35 years), B (36-50 years) and C (&gt;50 years). Age, ethnicity, staging, lymph nodes status, micrometastasis in negative lymph nodes, tumor size, tumor grade, hormone receptor status were extracted. Data and survival were analyzed using chi square, Kaplan-Meier, Life table, and Cox proportional hazard model. The primary outcome was 5-year cancer-specific survival. Results: A total of 248,280 patients were included in the study, group A, B and C making 2.8%, 25.5% and 71.7% of study subjects respectively. The median tumor size was 2.4, 1.9, and 1.6 cm in groups A, B and C respectively (p=0.0001). Positive lymph nodes were seen in 52.5%, 43% and 34% in groups A, B and C respectively (p=0.0001). Regional disease was seen in 47.5%, 39.5% and 29.9% in groups A, B and C respectively (p=0.0001). Higher Grade histology was seen in 63.5%, 44.3% and 33.8% in groups A, B and C respectively (p=0.0001). ER-PR negative were found in 42.1%,26.4%, 22.6% of Groups A, B and C respectively (p=0.0001). Five year cancer specific survival was 82%, 89%, 86% in groups A, B and C respectively (p=0.0001). Independent prognostic factors are given in the table. Conclusions: Breast cancer is uncommon among young women (age &lt;35). Compared to other age groups, breast cancer in young women presents with bigger tumor, higher nodal positivity, an advanced stage, higher tumor grade, higher hormone receptor negativity, and worse 5-year cancer-specific survival. [Table: see text]