Longitudinal Risk Analysis of Second Primary Cancer after Curative Treatment in Patients with Rectal Cancer.

Predicting and improving the response of rectal cancer to second primary cancers (SPCs) remains an active and challenging field of clinical research. Identifying predictive risk factors for SPCs will help guide more personalized treatment strategies. In this study, we propose that experience data be used as evidence to support patient-oriented decision-making. The proposed model consists of two main components: a pipeline for extraction and classification and a clinical risk assessment. The study includes 4402 patient datasets, including 395 SPC patients, collected from three cancer registry databases at three medical centers; based on literature reviews and discussion with clinical experts, 10 predictive variables were considered risk factors for SPCs. The proposed extraction and classification pipelines that classified patients according to importance were age at diagnosis, chemotherapy, smoking behavior, combined stage group, and sex, as has been proven in previous studies. The C5 method had the highest predicted AUC (84.88%). In addition, the proposed model was associated with a classification pipeline that showed an acceptable testing accuracy of 80.85%, a recall of 79.97%, a specificity of 88.12%, a precision of 85.79%, and an F1 score of 79.88%. Our results indicate that chemotherapy is the most important prognostic risk factor for SPCs in rectal cancer survivors. Furthermore, our decision tree for clinical risk assessment illuminates the possibility of assessing the effectiveness of a combination of these risk factors. This proposed model may provide an essential evaluation and longitudinal change for personalized treatment of rectal cancer survivors in the future.

Predictive value of FCGBP expression for treatment response and survival in rectal cancer patients undergoing chemoradiotherapy.

Despite neoadjuvant chemoradiotherapy (CRT) being the established standard for treating advanced rectal cancer, clinical outcomes remain suboptimal, necessitating the identification of predictive biomarkers for improved treatment decisions. Previous studies have hinted at the oncogenic properties of the Fc fragment of IgG binding protein (FCGBP) in various cancers; however, its clinical significance in rectal cancer remains unclear. In this study, we first conducted an analysis of a public transcriptome comprising 46 rectal cancer patients. Focusing on cell adhesion during data mining, we identified FCGBP as the most upregulated gene associated with CRT resistance. Subsequently, we assessed FCGBP immunointensity using immunohistochemical staining on 343 rectal cancer tissue blocks. Elevated FCGBP immunointensity correlated with lymph node involvement before treatment (p = 0.001), tumor invasion, and lymph node involvement after treatment (both p < 0.001), vascular invasion (p = 0.001), perineural invasion (p = 0.041), and reduced tumor regression (p < 0.001). Univariate analysis revealed a significant association between high FCGBP immunoexpression and inferior disease-specific survival, local recurrence-free survival, and metastasis-free survival (all p ≤ 0.0002). Furthermore, high FCGBP immunoexpression independently emerged as an unfavorable prognostic factor for all three survival outcomes in the multivariate analysis (all p ≤ 0.025). Enriched pathway analysis substantiated the role of FCGBP in conferring resistance to radiation. In summary, our findings suggest that elevated FCGBP immunoexpression in rectal cancer significantly correlates with a poor response to CRT and diminished patient survival. FCGBP holds promise as a valuable prognostic biomarker for rectal cancer patients undergoing CRT.

Comparative survival analysis of bladder preservation therapy versus radical cystectomy in muscle-invasive bladder cancer.

BACKGROUND: Bladder preservation therapy is an alternative to radical cystectomy in patients with muscle-invasive bladder cancer (MIBC). The purpose of this study is to compare survival outcomes between bladder preservation therapy and radical cystectomy in MIBC patients using an Asian nationwide cancer registry database. METHODS: From the Taiwan Cancer Registry database and the Taiwan National Health Insurance Research Database, we identified bladder cancer patients from 2008 to 2018. The patients with urothelial carcinoma and clinical stage T2-T4aN0-1 M0 were included. Propensity score matching by age, gender, clinical stage, cT classification, and Charlson Comorbidity Index score was used between those receiving bladder preservation therapy or radical cystectomy. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were compared using the Kaplan-Meier method. Multivariate Cox regression models were used to determine the predictive factors of OS, CSS, and DFS. RESULTS: Following the propensity score matching, 393 MIBC patients were analyzed, 131 (33.3%) receiving bladder preservation therapy and 262 (66.7%) receiving radical cystectomy. After 5 years of the follow-up period the overall duration was with a median of 15.6 months. The treatment groups did not differ significantly in OS, CSS, and DFS (p = 0.2681, 0.7208, and 0.3616, respectively). In multivariable Cox regression models, bladder preservation therapy remained non-inferior to radical cystectomy in OS (adjusted hazard ratio [aHR] 1.08; 95% confidence interval [CI], 0.77-1.50; p = 0.6689), CSS (aHR, 1.06; 95% CI, 0.72-1.57; p = 0.7728), and DFS (aHR, 0.76; 95% CI, 0.46-1.27; p = 0.2929). Additionally, among patients ≥80 years, the use of bladder preservation therapy compared with radical cystectomy resulted in an equivalent OS, CSS and DSS. CONCLUSION: In Asian populations, bladder preservation therapy yielded similar survival outcomes as radical cystectomy in MIBC patients. Based on the results, it is evident that a multidisciplinary approach and shared decision-making are recommended for bladder cancer treatment.

REG3A overexpression functions as a negative predictive and prognostic biomarker in rectal cancer patients receiving CCRT.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is suggested before resection surgery in the control of rectal cancer. Unfortunately, treatment outcomes are widely variable and highly patient-specific. Notably, rectal cancer patients with distant metastasis generally have a much lower survival rate. Accordingly, a better understanding of the genetic background of patient cohorts can aid in predicting CCRT efficacy and clinical outcomes for rectal cancer before distant metastasis. METHODS: A published transcriptome dataset (GSE35452) (n=46) was utilized to distinguish prospective genes concerning the response to CCRT. We recruited 172 rectal cancer patients, and the samples were collected during surgical resection after CCRT. Immunohistochemical (IHC) staining was performed to evaluate the expression level of regenerating family member 3 alpha (REG3A). Pearson's chi-squared test appraised the relevance of REG3A protein expression to clinicopathological parameters. The Kaplan-Meier method was utilized to generate survival curves, and the log-rank test was performed to compare the survival distributions between two given groups. RESULTS: Employing a transcriptome dataset (GSE35452) and focusing on the inflammatory response (GO: 0006954), we recognized that REG3A is the most significantly upregulated gene among CCRT nonresponders (log2 ratio=1.2472, p=0.0079). Following IHC validation, high immunoexpression of REG3A was considerably linked to advanced post-CCRT tumor status (p<0.001), post-CCRT lymph node metastasis (p=0.042), vascular invasion (p=0.028), and low-grade tumor regression (p=0.009). In the multivariate analysis, high immunoexpression of REG3A was independently correlated with poor disease-specific survival (DSS) (p=0.004) and metastasis-free survival (MeFS) (p=0.045). The results of the bioinformatic analysis also supported the idea that REG3A overexpression is implicated in rectal carcinogenesis. CONCLUSION: In the current study, we demonstrated that REG3A overexpression is correlated with poor CCRT effectiveness and inferior patient survival in rectal cancer. The predictive and prognostic utility of REG3A expression may direct patient stratification and decision-making more accurately for those patients.

Downregulation of TAZ elicits a mitochondrial redox imbalance and ferroptosis in lung epithelial cells exposed to diesel exhaust particles.

Mitochondrial dysfunction was reported to be involved in the development of lung diseases including chronic obstructive pulmonary disease (COPD). However, molecular regulation underlying metabolic disorders in the airway epithelia exposed to air pollution remains unclear. In the present study, lung bronchial epithelial BEAS-2B and alveolar epithelial A549 cells were treated with diesel exhaust particles (DEPs), the primary representative of ambient particle matter. This treatment elicited cell death accompanied by induction of lipid reactive oxygen species (ROS) production and ferroptosis. Lipidomics analyses revealed that DEPs increased glycerophospholipid contents. Accordingly, DEPs upregulated expression of the electron transport chain (ETC) complex and induced mitochondrial ROS production. Mechanistically, DEP exposure downregulated the Hippo transducer transcriptional co-activator with PDZ-binding motif (TAZ), which was further identified to be crucial for the ferroptosis-associated antioxidant system, including glutathione peroxidase 4 (GPX4), the glutamate-cysteine ligase catalytic subunit (GCLC), and glutathione-disulfide reductase (GSR). Moreover, immunohistochemistry confirmed downregulation of GPX4 and upregulation of lipid peroxidation in the bronchial epithelium of COPD patients and Sprague-Dawley rats exposed to air pollution. Finally, proteomics analyses confirmed alterations of ETC-related proteins in bronchoalveolar lavage from COPD patients compared to healthy subjects. Together, our study discovered that involvement of mitochondrial redox dysregulation plays a vital role in pulmonary epithelial cell destruction after exposure to air pollution.

SYNPO2 upregulation is an unfavorable prognostic factor for nasopharyngeal carcinoma patients.

Nasopharyngeal carcinoma (NPC) is the most common malignant neoplasm of the nasopharynx. Despite improvements in the clinical treatment strategies for NPC, NPC patients usually have poor survival rates because of late diagnosis, tumor metastasis, and recurrence. Therefore, the identification of potential diagnostic and prognostic markers for NPC is imperative. We investigated the differential expression of cell adhesion-related genes (gene ontology:0003779) and tumorigenesis-related genes (GSE12452) in patients with NPC. The correlations between synaptopodin-2 (SYNPO2) immune expression and clinicopathological features were analyzed using Pearson chi-square test. Multivariate analysis was performed using Cox proportional hazards model. SYNPO2 expression was significantly higher in NPC tumor tissues than in nontumor tissues. High SYNPO2 expression was significantly associated with the advanced disease stage (P = .006). Univariate analysis showed that high expression of SYNPO2 was associated with poor disease-specific survival, distal metastasis-free survival, and local recurrence-free survival in patients with NPC. Notably, our multivariate analysis demonstrated that high SYNPO2 expression was substantially correlated with inferior disease-specific survival (hazard ratio = 1.968, P = .012) and local recurrence-free survival (hazard ratio = 3.386, P = .001). Overall, our findings reveal that SYNPO2 may aid in the development of potential prognostic biomarkers for NPC patients.

Obesity-mediated upregulation of the YAP/IL33 signaling axis promotes aggressiveness and induces an immunosuppressive tumor microenvironment in breast cancer.

Obesity is a well-known risk factor for breast cancer formation and is associated with elevated mortality and a poor prognosis. An obesity-mediated inflammatory microenvironment is conducive to the malignant progression of tumors. However, the detailed molecular mechanism is still needed to be clarified. Herein, we identified that breast cancer cells from mice with diet-induced obesity exhibited increased growth, invasiveness, and stemness capacities. A transcriptome analysis revealed that expressions of interleukin 33 (IL33) signaling pathway-related genes were elevated in obesity-associated breast cancer cells. Importantly, IL33 expression was significantly associated with the yes-associated protein (YAP) signature, and IL33 was transcriptionally regulated by YAP. Suppression of IL33 reduced tumor migration and invasion, while the addition of IL33 activated nuclear factor (NF)-κB signaling and revived tumor mobility in YAP-silenced cells. Furthermore, suppression of YAP attenuated IL33 expression which was accompanied by relief of obesity-mediated immunosuppression. Clinical analyses showed that IL33 expression was markedly associated with macrophage and regulatory T cell infiltration. These findings reveal a crucial role of the YAP/IL33 axis in promoting aggressiveness and immunosuppression of obesity-associated breast cancer progression.

No survival benefit from adding chemotherapy to adjuvant radiation in advanced major salivary gland cancer.

This study aimed to compare survival of patients with advanced major salivary gland cancers treated with adjuvant chemoradiation therapy (CRT) versus radiotherapy (RT) alone, after surgical resection. The Taiwan Cancer Registry database was used to identify patients (2009-2017) with advanced (T3-4 or nodal positivity) major salivary gland cancers, treated post-surgically with adjuvant CRT or RT alone. Overall survival (OS) and disease-specific survival (DSS) evaluated using Kaplan-Meier. Stratified analyses conducted on clinicopathological features. A total of 395 patients were analyzed: 178 (45.1%) received adjuvant CRT; 217 (54.9%) received adjuvant RT alone. Median radiation dose was 66 Gy in 33 fractions. Cisplatin was most common chemotherapy regimen. After a median follow-up of 3.37 years, there was no significant difference in OS or DSS (p = 0.1354 and 0.3361, respectively) between groups. Adding chemotherapy to adjuvant RT was not significantly associated with improved OS (adjusted hazard ratio [aHR] 0.94; 95% CI 0.72-1.23) and DSS (aHR 0.96; 95% CI 0.72-1.28). Stratified analysis of clinicopathological features found no significant advantages for improved OS or DSS from adding chemotherapy to adjuvant RT. Thus, in this population database, the use of chemotherapy provided limited survival benefits in advanced major salivary gland cancers after surgical resection.

High Expression of Folate Receptor Alpha (FOLR1) is Associated With Aggressive Tumor Behavior, Poor Response to Chemoradiotherapy, and Worse Survival in Rectal Cancer.

Objectives: Recently, molecular medicine targeting Folate Receptor Alpha (FOLR1), which mediates intracellular folate uptake and tumor cell proliferation, has been identified in several malignancies. However, the association between FOLR1 expression and rectal cancer remains unclear. Methods: Immunostaining of FOLR1 was performed on biopsy specimens from 172 rectal cancer patients undergoing preoperative chemoradiotherapy (CRT). FOLR1 expression was measured and divided into low (0+-2+) or high (3+-4+) level. Correlations between FOLR1 status and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival, and metastasis-free survival (MeFS) were analyzed, retrospectively. Results: High FOLR1 expression was significantly associated with advanced post-treatment tumor and nodal status (T3-4; N1-2, P = .001), vascular invasion (P = .042), perineural invasion (P = .012), and poor regression change after CRT (P = .001). In uni- and multi-variable survival analysis, FOLR1 overexpression remained a significant predictor of lower DSS (hazard ratio [HR], 2.328; 95% confidence interval [CI], 1.014-5.344; P = .046) and MeFS (HR, 2.177; 95% CI, 1.000-1.1286; P = .050). Conclusion: These results indicate that high FOLR1 status is associated with aggressive tumor behavior, poor response to CRT, and worse survival. Therefore, FOLR1 expression at initial biopsy may be useful in predicting outcomes and also be a target for the exploration of FOLR1-based therapeutic agents.

Upregulated Ubiquitin D is a Favorable Prognostic Indicator for Rectal Cancer Patients Undergoing Preoperative Concurrent Chemoradiotherapy.

Purpose: For locally advanced rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) allows tumor downstaging and makes curative radical proctectomy possible. However, we lack a genetic biomarker to predict cancer prognosis or treatment response. We investigated the association between ubiquitin D (UBD) expression and clinical outcomes in rectal cancer patients receiving CCRT. Patients and Methods: We analyzed the genes associated with the protein modification process (GO:0036211) and identified the UBD gene as the most relevant among the top 7 differentially expressed genes associated with CCRT resistance. We collected tissue specimens from 172 rectal cancer patients who had received CCRT followed by a curative proctectomy. We examine the relationship between UBD expression and patient characteristics, pathological findings, and patient survival, such as metastasis-free survival (MeFS) and disease-specific survival. Results: Upregulated UBD expression was associated with lower pre-CCRT tumor T stage (P = 0.009), lower post-CCRT tumor T stage (P < 0.001), lower post-CCRT nodal stage (P < 0.001), less vascular invasion (P = 0.015), and better tumor regression (P < 0.001). Using univariate analysis, we found that high UBD expression was correlated with better disease-free survival (DFS) (P < 0.0001), local recurrence-free survival (LRFS) (P < 0.0001) and MeFS (P < 0.0001). Moreover, multivariate analysis demonstrated that high UBD expression was associated with superior DFS (P < 0.001), LRFS (P = 0.01), and MeFS (P = 0.004). Conclusion: UBD upregulation was linked to better clinical prognosis, favorable pathological features, and good treatment response in rectal cancer patients undergoing CCRT. These results suggest UBD is a biomarker for rectal cancer.

Overexpression of Dehydrogenase/Reductase 9 Predicts Poor Response to Concurrent Chemoradiotherapy and Poor Prognosis in Rectal Cancer Patients.

Objective: To reduce the risk of locoregional recurrence, the addition of neoadjuvant concurrent chemoradiotherapy (CCRT) is recommended before surgical management for rectal cancer patients. However, despite identical tumor histology, individual patient response to neoadjuvant CCRT varies greatly. Accordingly, a comprehensive molecular characterization that is used to predict CCRT efficacy is instantly needed. Methods: Pearson's chi-squared test was utilized to correlate dehydrogenase/reductase 9 (DHRS9) expression with clinicopathological features. Survival curves were created applying the Kaplan-Meier method, and the log-rank test was conducted to compare prognostic utility between high and low DHRS9 expression groups. Multivariate Cox proportional hazards regression analysis was applied to identify independent prognostic biomarkers based on variables with prognostic utility at the univariate level. Results: Utilizing a public transcriptome dataset, we identified that the DHRS9 gene is the most considerably upregulated gene related to epithelial cell differentiation (GO: 0030855) among rectal cancer patients with CCRT resistance. Employing immunohistochemical staining, we also demonstrated that high DHRS9 immunoexpression is considerably associated with an aggressive clinical course and CCRT resistance in our rectal cancer cohort. Among all variables with prognostic utility at the univariate level, only high DHRS9 immunoexpression was independently unfavorably prognostic of all three endpoints (all p ≤ 0.048) in the multivariate analysis. In addition, applying bioinformatic analysis, we also linked DHRS9 with unrevealed functions, such as keratan sulfate and mucin synthesis which may be implicated in CCRT resistance. Conclusion: Altogether, DHRS9 expression may serve as a helpful predictive and prognostic biomarker and assist decision-making for rectal cancer patients who underwent neoadjuvant CCRT.

The effect of adjuvant radiotherapy on clinical outcomes in early major salivary gland cancer.

BACKGROUND: This study investigated the effects of adjuvant radiotherapy on outcomes in early-stage major salivary gland cancers. METHODS: A total of 655 patients were identified, including 355 (54.2%) received adjuvant radiotherapy and 300 (45.8%) had surgery alone. The effect of adjuvant radiotherapy on 5-year locoregional recurrence and disease-specific survival (DSS) was calculated using the Kaplan-Meier method, Wilcoxon rank sum test, and Cox proportional hazards model. RESULTS: There were no significant differences in locoregional recurrence and DSS between patients receiving adjuvant radiotherapy and those not in both univariate and multivariable analysis. Although patients with positive margin status had a higher locoregional recurrence and those with moderate/poor differentiation had a worse DSS, stratified analysis still indicated there were no protective effects from the use of adjuvant radiotherapy. CONCLUSIONS: The use of adjuvant radiation therapy was not associated with improved locoregional recurrence and DSS, even for those with high-risk histopathological factors.

Roundabout Guidance Receptor 1 Is an Emerging Prognostic Biomarker for Nasopharyngeal Carcinoma.

Background: Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the nasopharynx with high morbidity and mortality in Southeast Asia and south of China. Roundabout guidance receptor 1 (ROBO1) can regulate axonogenesis (axon-like protrusion), which may play an important role in migration. However, the roles of ROBO1 in NPC have not been clarified. Methods: A comparative analysis employing the NPC transcriptome (GSE12452) and the axonogenesis-related genes (GO: 0050772) was performed. In total, 124 tissue blocks from patients primarily diagnosed as NPC (1993-2002) were examined using immunohistochemical staining. The connections between clinicopathological variables and protein immunoexpression were analyzed by Pearson's chi-square test. The Kaplan-Meier method with a log-rank test was employed to plot survival curves. Multivariate analysis was performed using the Cox proportional hazards model to identify independent prognostic biomarker. Results: According to transcriptome analysis, we found that ROBO1 is significantly highly expressed in NPC tissues compared with normal tissues. The immunohistochemistry (IHC) staining showed that high expression of ROBO1 was significantly related to primary tumor (T1T2 and T3T4) (P = .024), nodal metastasis status (N0N1 and N2N3) (P = .030), stage (I-II and III-IV) (P = .019), and histological grade (keratinizing, non-keratinizing, and undifferentiated) (P = .065). Importantly, NPC patients with high ROBO1 expression had poorer disease-specific survival (DSS) (P = .0001), distal metastasis-free survival (DMeFS) (P < .0001), and local recurrence-free survival (LRFS) (P = .0001) compared with NPC patients with low ROBO1 expression through the uni-/multivariate and the Kaplan-Meier survival analyses. Conclusion: Our report indicates that ROBO1 might be a potential prognostic biomarker for NPC.

Formin-Like 2 Is a Potential Biomarker of Poor Prognosis in Nasopharyngeal Carcinoma.

Introduction: Nasopharyngeal carcinoma (NPC) is the most common malignant tumor in southern China and Southeast Asia. Although substantial research on NPC has been conducted, the resulting improvement in clinical outcomes remains very disappointing. NPC treatment typically involves radiation therapy and chemotherapy, but the high incidence of metastasis and recurrence in NPC patients result in poor survival. Therefore, identifying potential biomarkers and discovering therapeutic targets are necessary to design tailored treatments based on the genetic profiles of NPC patients. Methods: Correlations of protein immunostaining with clinicopathological features were analyzed by Pearson's χ2 test. The Kaplan-Meier method with a log-rank test was used to generate survival curves. Multivariate analysis was performed using the Cox proportional hazards model. Results: In this study, we comparatively analyzed cytoskeletal organization and biogenesis (GO:0007010) and tumorigenesis in the NPC transcriptome (GSE12452) and found that formin-like 2 (FMNL2) expression was significantly upregulated in NPC tumor tissues. Moreover, high FMNL2 expression was significantly correlated with primary tumor stage (p = 0.001), lymph node status (p = 0.004), cancer stage (p = 0.006), and histological grade (p = 0.040). More importantly, high FMNL2 expression was significantly correlated with poor survival in NPC patients according to univariate analysis and multivariate analysis. Conclusion: This study reveals that FMNL2 may be an important potential biomarker for evaluating the prognosis of NPC patients.

Adjuvant chemotherapy and survival outcomes in rectal cancer patients with good response (ypT0-2N0) after neoadjuvant chemoradiotherapy and surgery: A retrospective nationwide analysis.

Background: For rectal cancer, it remains unclear how to incorporate tumor response to neoadjuvant chemoradiotherapy (nCRT) when deciding whether to give adjuvant chemotherapy. In this study, we aim to determinate the survival benefit of adjuvant chemotherapy for rectal cancer patients with good response (ypT0-2N0) after nCRT and surgery. Methods: The study cohort included 720 rectal cancer patients who had good response (ypT0-2N0) after nCRT and surgery, who did or did not receive adjuvant chemotherapy between January 2007 and December 2017, from the Taiwan Cancer Registry and National Health Insurance Research database. The Kaplan-Meier method, log-rank tests, and Cox regression analysis were performed to investigate the effect of adjuvant chemotherapy on 5-year overall survival (OS) and disease-free survival (DFS). Results: Of 720 patients, 368 (51.1%) received adjuvant chemotherapy and 352 (48.9%) did not. Patients who received adjuvant chemotherapy were more likely to be female, younger (≤ 65), with advanced clinical T (3-4)/N (1-2) classification and ypT2 classification. No significant difference in 5-year OS (p=0.681) or DFS (p=0.942) were observed by receipt of adjuvant chemotherapy or not. Multivariable analysis revealed adjuvant chemotherapy was not associated with better OS (adjusted hazard ratio [aHR], 1.03; 95% Confidence Interval [CI], 0.88-1.21) or DFS (aHR, 1.05; 95% CI, 0.89-1.24). Stratified analysis for OS and DFS found no significant protective effect in the use of adjuvant chemotherapy, even for those with advanced clinical T or N classification. Conclusion: Adjuvant chemotherapy may be omitted in rectal cancer patients with good response (ypT0-2N0) after nCRT and surgery.

Optimal Lymph Node Yield for Survival Prediction in Rectal Cancer Patients After Neoadjuvant Therapy.

PURPOSE: A lymph node (LN) yield ≥12 is required to for accurate determination of nodal status for colorectal cancer but cannot always be achieved after neoadjuvant therapy. This study aims to determine the difference in LN yield from rectal cancer patients treated with and without neoadjuvant therapy and the effects of specific LN yields on survival. PATIENTS AND METHODS: The study cohort included a total of 4344 rectal cancer patients treated between January 2007 and December 2015, 2260 (52.03%) of whom received neoadjuvant therapy. Data were retrieved from the Taiwan nationwide cancer registry database. The minimum acceptable LN yield below 12 was investigated using the maximum area under the ROC curve. RESULTS: The median LN yield was 12 (8-17) for patients who received neoadjuvant therapy and 17 (13-24) for those who did not. The recommended LN yield ≥12 was achieved in 82.73% of patients without and 57.96% of those with neoadjuvant therapy (p < 0.0001). Patients with LN yield ≥12 had a higher OS probability than did those with LN <12 (OR, 1.33; 95% CI, 1.06-1.66; p = 0.0124). However, the predictive accuracy for survival was greater for LN yield ≥10 (AUC, 0.7767) than cut-offs of 12, 8, or 6, especially in patients with pathologically-negative nodes (AUC, 0.7660). CONCLUSION: Neoadjuvant therapy significantly reduces the LN yield in subsequent surgery. A lower yield (LN ≥ 10) may be adequate for nodal evaluation in rectal cancer patients after neoadjuvant therapy.

Overexpression of MLPH in Rectal Cancer Patients Correlates with a Poorer Response to Preoperative Chemoradiotherapy and Reduced Patient Survival.

Data mining of a public transcriptomic rectal cancer dataset (GSE35452) from the Gene Expression Omnibus, National Center for Biotechnology Information identified the melanophilin (MLPH) gene as the most significant intracellular protein transport-related gene (GO:0006886) associated with a poor response to preoperative chemoradiation. An MLPH immunostain was performed on biopsy specimens from 172 rectal cancer patients receiving preoperative chemoradiation; samples were divided into high- and low-expression groups by H-scores. Subsequently, the correlations between MLPH expression and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS) were analyzed. MLPH expression was significantly associated with CEA level (p = 0.001), pre-treatment tumor status (p = 0.022), post-treatment tumor status (p < 0.001), post-treatment nodal status (p < 0.001), vascular invasion (p = 0.028), and tumor regression grade (p < 0.001). After uni- and multi-variable analysis of five-year survival, MLPH expression was still associated with lower DSS (hazard ratio (HR), 10.110; 95% confidence interval (CI), 2.178-46.920; p = 0.003) and MeFS (HR, 5.621; 95% CI, 1.762-17.931; p = 0.004). In conclusion, identifying MLPH expression could help to predict the response to chemoradiation and survival, and aid in personal therapeutic modification.

The new SRS/FSRT technique HyperArc for benign brain lesions: a dosimetric analysis.

To evaluate the potential benefit of HyperArc (HA) fractionated stereotactic radiotherapy (FSRT) for the benign brain lesion. Sixteen patients with a single deep-seated, centrally located benign brain lesion treated by CyberKnife (CK, G4 cone-based model) were enrolled. Treatment plans for HA with two different optimization algorithms (SRS NTO and ALDO) and coplanar RapidArc (RA) were generated for each patient to meet the corresponding treatment plan criteria. These four FSRT treatment plans were divided into two groups-the homogeneous delivery group (HA-SRS NTO and coplanar RA) and the inhomogeneous delivery group (HA-ALDO and cone-based CK)-to compare for dosimetric outcomes. For homogeneous delivery, the brain V5, V12, and V24 and the mean brainstem dose were significantly lower with the HA-SRS NTO plans than with the coplanar RA plans. The conformity index, high and intermediate dose spillage, and gradient radius were significantly better with the HA-SRS NTO plans than with the coplanar RA plans. For inhomogeneous delivery, the HA-ALDO exhibited superior PTV coverage levels to the cone-based CK plans. Almost all the doses delivered to organs at risk and dose distribution metrics were significantly better with the HA-ALDO plans than with the cone-based CK plans. Good dosimetric distribution makes HA an attractive FSRT technique for the treatment of benign brain lesions.

High SPIN4 Expression Is Linked to Advanced Nodal Status and Inferior Prognosis in Nasopharyngeal Carcinoma Patients.

Nasopharyngeal carcinoma (NPC), characterized by the infiltration of lymphocytes, is a malignancy derived from the epithelium of the nasopharynx. Despite its sensitivity to radiation and chemotherapy, NPC has a high propensity for recurrence and metastasis. Although lymph node levels have been indicated as an independent prognostic factor for NPC, there has been no precise prognostic biomarker to predict clinical outcomes for NPC before advanced disease. In the present study, we surveyed differentially expressed genes in NPC via the next-generation sequencing (NGS)-based Oncomine database and identified the spindlin family member 4 (SPIN4) gene as the most relevant to advanced nodal status. We collected 124 tumor samples from NPC patients receiving biopsy, and the expression level of SPIN4 was evaluated by immunohistochemistry. The results showed that tumors with high SPIN4 expression were significantly correlated with advanced nodal status (p < 0.001) and advanced AJCC stages (p < 0.001). High SPIN4 expression in tumor samples was an unfavorable prognostic factor for all three endpoints at the univariate level: disease-specific survival (DSS), distal metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) (all p < 0.05). High SPIN4 expression remained independently prognostic of worse DMeFS (p = 0.049) at the multivariate level. Using bioinformatics analysis, we further found that high SPIN4 level may link tight junctions to cancer cell survival. Collectively, these results imply that high SPIN4 expression is linked to an aggressive clinical course, including advanced nodal status and poor survival in NPC patients, emphasizing the promising prognostic utility of SPIN4 expression.

Adjuvant Radiotherapy Significantly Increases Neck Control and Survival in Early Oral Cancer Patients with Solitary Nodal Involvement: A National Cancer Registry Database Analysis.

We assessed the role of adjuvant radiotherapy on neck control and survival in patients with early oral cancer with solitary nodal involvement. We identified pT1-2N1 oral cancer patients with or without adjuvant radiotherapy from the 2007-2015 Taiwan Cancer Registry database. The effect of adjuvant radiotherapy on 5-year neck control, overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method, log-rank tests, and Cox regression analysis. Of 701 patients identified, 505 (72.0%) received adjuvant radiotherapy and 196 (28.0%) had surgery alone. Patients receiving adjuvant radiotherapy were more likely to be aged <65 years, pT2 stage, poorly graded and without comorbid conditions (all, p < 0.05). The 5-year OS and DFS differed significantly by receipt of adjuvant radiotherapy. Multivariable analysis showed adjuvant radiotherapy significantly associated with better 5-year OS (adjusted hazard ratio (aHR), 0.72; 95% confidence interval (CI), 0.54-0.97; p = 0.0288) and DFS (aHR, 0.64; 95% CI, 0.48-0.84; p = 0.0016). Stratified analysis indicated the greatest survival advantage for both 5-year OS and DFS in those with pT2 classification (p = 0.0097; 0.0009), and non-tongue disease (p = 0.0195; 0.0158). Moreover, adjuvant radiotherapy significantly protected against neck recurrence (aHR, 0.30; 95% CI, 0.18-0.51; p < 0.0001). Thus, adjuvant radiotherapy is associated with improved neck control and survival in these early oral cancer patients.