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Introduction: Limited data exist on interphase fluorescent in situ hybridization (iFISH)-based survival outcomes in newly diagnosed multiple myeloma (NDMM) from India. Objectives: To study the demographics and iFISH-based survival outcomes in NDMM patients treated with proteasome inhibitors from a community-based cancer setup. Materials and Methods: We reviewed the records of 25 patients treated with proteasome inhibitors between June 2017 and April 2023 using five high-risk (HR) iFISH markers based on mSMART 3.0. Results: The median age was 60 years (range 34–87). HR iFISH was detected in 12 (48%) patients. With a median follow-up of 27 months, the overall response at the last follow-up was 80% (very good partial response - 52%, complete remission - 20%, and partial response - 8%), with 8 (32%) relapses. Twenty (80%) patients remain alive, with five deaths in HR (sepsis [ n = 3]). The 2.5-year overall survival in HR and standard risk was 55.6% ± 15.2% and 100% (P = 0.01), and event-free survival was 32.4% ± 16.5% and 77.8% ± 13.8% (P = 0.02), respectively. Conclusions: Using limited iFISH HR markers helps in the early and effective stratification of NDMM in the real world. Sepsis remains an important cause of mortality in an Indian setup. [ABSTRACT FROM AUTHOR]

Objectives: Laryngeal squamous cell carcinoma (LSCC) is a common squamous cell carcinoma of the head and neck with no reliable diagnostic biomarkers. However, recent studies have shown that inflammation plays an essential role in tumor development, and several inflammation-based biomarkers have been shown to have prognostic value. This study aimed to investigate the auxiliary value of fibrinogen (FIB), fibrinogen degradation products (FDP), and lymphocyte/monocyte ratio (LMR) in LSCC diagnosis and prognosis. Methods: Clinical data from 218 patients recently diagnosed with LSCC and 207 diagnosed with benign laryngeal lesions (BLLs) were retrospectively reviewed. Potential diagnostic biomarkers were evaluated using univariate and multivariate analyses; receiver operating characteristic (ROC) curve analysis was used to identify cut-off values and diagnostic efficiency. Least absolute shrinkage and selection operator (LASSO) Logistic regression analysis was used to screen for independent risk factors to construct a diagnostic nomogram. The chi-squared test and Kaplan–Meier method were performed to investigate the correlation of clinicopathological characteristics and 3-year overall survival (OS) with FIB, FDP, and LMR in patients with LSCC. Results: FIB, FDP, and LMR levels were significantly different between the LSCC and BLL groups (P <.001), and all were independent risk factors for LSCC. The area under the ROC curve of the diagnostic nomogram was.894. Additionally, FIB, FDP, and LMR were correlated with some invasive clinicopathological features, and LMR ≥4.29 was associated with reduced OS (P =.038). Conclusion: FIB, FDP, and LMR demonstrated potential as biomarkers for the diagnosis and prognosis of LSCC; however, further studies are needed to confirm their efficacy. [ABSTRACT FROM AUTHOR]

Background: Soft tissue sarcoma (STS) is a rare malignancy that affects soft tissues. It encompasses various subtypes and requires different treatment strategies. Doxorubicin is a commonly used anthracycline in the management of localized and metastatic STS. However, high doses of doxorubicin are associated with cardiotoxicity, which can significantly impact patients' long-term outcomes. This study aimed to evaluate doxorubicin's effect on cardiac function in patients with sarcoma and to correlate the frequency of cardiotoxicity with potential risk factors. Methods: A retrospective analysis was conducted on patients with sarcoma who were treated with doxorubicin between 2016 and 2022 at King Abdulaziz Medical City in Saudi Arabia. Patient demographic information, comorbidities, cardiac measurements, laboratory values, systemic therapy, and treatment outcomes were collected from electronic medical records. A statistical analysis was performed to assess the association between cardiotoxicity and various factors. Results: A total of 133 patients were included in the study, with a median age of 30 years. Cardiotoxicity was observed in 9% of the patients. Female patients had a significantly higher risk of developing cardiotoxicity. Patients with a higher Eastern Cooperative Oncology Group (ECOG) performance status and lower troponin I levels also had an increased risk of cardiotoxicity. However, there was no significant association between cardiotoxicity and the number of chemotherapy cycles, total cumulative dose of doxorubicin, or history of radiation. Furthermore, patients with cardiotoxicity had a higher risk of mortality. The overall survival of the patients was 18 months. Conclusion: Doxorubicin-associated cardiotoxicity is a concern for patients with sarcoma. Female patients and patients with a higher ECOG performance status are at an increased risk of developing cardiotoxicity. Careful monitoring and risk assessment are crucial for mitigating the adverse effects of doxorubicin treatment in patients with sarcoma. Future studies are warranted to validate these findings and explore preventive strategies for doxorubicin-induced cardiotoxicity in patients with sarcoma. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) patients have a poor prognosis after radio-frequency ablation (RFA), and investigating the risk factors affecting RFA and establishing predictive models are important for improving the prognosis of HCC patients. Methods: Patients with HCC undergoing RFA in Shenzhen People's Hospital between January 2011 and December 2021 were included in this study. Using the screened independent influences on recurrence and survival, predictive models were constructed and validated, and the predictive models were then used to classify patients into different risk categories and assess the prognosis of different categories. Results: Cox regression model indicated that cirrhosis (hazard ratio [HR] = 1.65), alpha-fetoprotein (AFP) ⩾400 ng/mL (HR = 2.03), tumor number (multiple) (HR = 2.11), tumor diameter ⩾20 mm (HR = 2.30), and platelets (PLT) ⩾ 244 (109/L) (HR = 2.37) were independent influences for recurrence of patients after RFA. On the contrary, AFP ⩾400 ng/mL (HR = 2.48), tumor number (multiple) (HR = 2.52), tumor diameter ⩾20 mm (HR = 2.25), PLT ⩾244 (109/L) (HR = 2.36), and hemoglobin (HGB) ⩾120 (g/L) (HR = 0.34) were regarded as independent influences for survival. The concordance index (C-index) of the nomograms for predicting disease-free survival (DFS) and overall survival (OS) was 0.727 (95% confidence interval [CI] = 0.770-0.684) and 0.770 (95% CI = 0.821-7.190), respectively. The prognostic performance of the nomograms was significantly better than other staging systems by analysis of the time-dependent C-index and decision curves. Each patient was scored using nomograms and influencing factors, and patients were categorized into low-, intermediate-, and high-risk groups based on their scores. In the Kaplan-Meier survival curve, DFS and OS were significantly better in the low-risk group than in the intermediate- and high-risk groups. Conclusions: The 2 prediction models created in this work can effectively predict the recurrence and survival rates of HCC patients following RFA. [ABSTRACT FROM AUTHOR]

Background: Induction chemotherapy (ICT) has become an initial treatment for head and neck squamous cell carcinoma (HNSCC). However, myelosuppression, an unavoidable side effect of ICT, significantly impacts follow-up treatment and prognosis. The main objective of this study is to identify the risk factors and predictors of myelosuppression and its different severity after ICT for ICT. Methods: We retrospectively reviewed medical records of 102 patients with hypopharyngeal cancer or oropharyngeal cancer who received initial ICT from 2013 to 2022. Univariate and multivariate logistic regression analyses were performed to identify risk factors for myelosuppression. Receiver-operating characteristic (ROC) curves were generated using the results of multiple logistic regression analysis to identify data with the highest sensitivity and lowest false-negative rate. Results: Pretreatment lymphocyte count (PLC) and the pretreatment platelet count (PPC) were identified as independent risk factors of myelosuppression (P <.05). Pretreatment hemoglobin count (PHC) was an independent risk factor for predicting myelosuppression in patients with grades III to IV disease. Patients with myelosuppression after ICT are more sensitive to chemotherapy. Conclusions: The PLC and PPC predicted myelosuppression in patients with HNSCC-administered ICT, and the PHC predicted grades III to IV myelosuppression. Myelosuppressed patients were more chemosensitive after ICT. [ABSTRACT FROM AUTHOR]

Background: The influence of the breast as the primary site on the outcome of diffuse large B-cell lymphoma (DLBCL) and further changes in therapeutic strategies remain unclear. We aimed to compare the outcomes between primary breast and non-breast DLBCL and analyze the genetic profiles of some of the study cohorts using next-generation sequencing. Methods: This matched-pair study reviewed the medical records of 19 patients with stage I and II primary breast DLBCL diagnosed between January 2005 and December 2021 on the basis of the Wiseman and Liao criteria, and we used 1:4 propensity score matching to identify patients with non-breast DLBCL as the control group. The overall response rate, progression-free survival (PFS), and overall survival (OS) were the outcome measures. Results: Patients with primary breast and non-breast DLBCL had a 5-year PFS of 72.6% and 86.9%, respectively (P =.206). These 2 groups also had comparable 5-year OS (86.9% vs 87.8%; P =.772). The breast as the primary site was not associated with inferior PFS (hazard ratio [HR]: 2.14; 95% CI: 0.66-6.96; P =.206) and OS (HR: 1.26; 95% CI: 0.27-5.93; P =.772). Conclusion: Patients with primary breast DLBCL and those with non-breast DLBCL had comparable PFS and OS under rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens. Further investigations of the mutation profile, its clinical impact, potential central nervous system relapse, and prognosis of primary breast DLBCL are required. [ABSTRACT FROM AUTHOR]

Background: The standard recommendation for neoadjuvant therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients is trastuzumab in combination with chemotherapy, but there is no current standard recommendation for appropriate chemotherapy regimens. This meta-analysis evaluated the efficacy and cardiac safety of the concurrent use of anti-HER2 targeted drugs and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancers. Methods: The pooled odds ratio (OR) rate for pathologic complete response (pCR), the pooled hazard ratio (HR) of overall survival (OS), and the left ventricular ejection fraction (LVEF) decline events were all calculated. Differences in efficacy, prognosis, and cardiac safety were compared between patients receiving an anthracycline-containing regimen (AB) and those treated with non-anthracycline-based (nAB) NAC. Results: A total of 1366 patients in 4 prospective and 3 retrospective studies were included in the meta-analysis. The pooled OR for pCR rate was 0.73 with a 95% confidence interval (CI) of 0.43 to 1.24 (P =.246). Subgroup analysis of low tumor burden cases showed no improvement in pCR rate for patients in the AB group compared with nAB, with the pooled OR rate being 0.73 with a 95% CI of 0.37 to 1.44 (P =.357). The 3-year OS rate was 95.63% and 95.54% in the AB and nAB groups, respectively, with no statistical difference (P =.157). There was a significant increase in the rate of LVEF decline of 19.07% in the AB group compared with 13.33% for the nAB group, with an HR of 1.62 and a 95% CI of 1.11 to 2.36 (P =.013). Conclusions: The addition of anthracyclines did not improve pCR rates and survival after neoadjuvant and the increased cardiotoxicity of anthracyclines further limited their application. This study showed that it was feasible to use anti-HER2 drugs without anthracyclines in neoadjuvant therapy for HER2-positive breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: Tribbles Homolog 3 (TRIB3) is a member of the pseudokinase family of tribbles and acts as an adaptor protein to regulate different cellular processes. Upregulation of TRIB3 expression was shown either as a favorable or an adverse prognostic factor in various adult malignancies. However, TRIB3 expression has not been examined in pediatric cancers. Neuroblastoma is the most common malignant solid tumor of childhood, which affects mostly children under 5 years old. Risk stratification of patients defined by International Neuroblastoma Risk Group was used to determine prognosis and treatment of the disease. This study aimed to examine the relationship between TRIB3 protein expression levels and clinicopathological features and survival of patients. Methods: TRIB3 protein expression was analyzed using immunohistochemical staining on formalin-fixed paraffin-embedded tissue samples of neuroblastoma patients (n = 56). Survival analyses were performed with Kaplan-Meier method and log-rank tests. Association between TRIB3 expression and clinicopathological characteristics were analyzed with Spearman's correlation. Results: Of the patients, 32.1% were in the low-risk group, 21.4% in the medium-risk group, and 46.4% in the high-risk group. Survival analysis was performed in the entire neuroblastoma patient group and sub-risk groups of neuroblastoma patients. In the entire patient group, there was no significant difference in overall survival (P =.202) and event-free survival (P =.172) between TRIB3-positive and -negative patients. However, when survival analyses were performed in each risk group, TRIB3 expression was significantly associated with higher overall survival (P =.034) and event-free survival (P =.032) in low-risk group neuroblastoma patients. Nevertheless, no association was found between TRIB3 expression and overall survival (P =.799) and event-free survival (P =.448) in high-risk neuroblastoma patients. Furthermore, a significant correlation was identified between 1p36 loss-of-heterozygosity and TRIB3 expression (P =.030). However, TRIB3 expression did not correlate with other clinicopathological features. Conclusion: TRIB3 expression is a potential predictive biomarker for low-risk neuroblastoma patients. [ABSTRACT FROM AUTHOR]

Objectives: The preoperative controlling nutritional status (pCONUT) score has been shown correlated with the prognosis of some cancerous diseases; however, little is known about the effect of pCONUT score on hypopharyngeal cancer (HPC). Therefore, the objective of our study was to demonstrate the relationship between the pCONUT score and the clinical outcome of patients with HPC. Patients and Methods: Ninety-four patients with HPC who underwent surgery between May 2012 and Dec 2020 were enrolled in this study. We evaluated retrospectively their pCONUT scores and calculated the cutoff value regarding the patients' overall survival using the X-tile software. Kaplan–Meier and Cox proportional hazard regression model were used to determine how the pCONUT score affected overall survival. Results: A cutoff level of 4 was determined to be optimal for the pCONUT score, by which the patients were grouped into high pCONUT score (≥4, n = 22, 23.4%) or low pCONUT score (<4, n = 72, 76.6%) groups. The univariate analysis showed that high pCONUT scores correlated with reduced overall survival (hazard ratio: 2.925, 95% confidence interval: 1.526-5.607, P =.001). Furthermore, the multivariate analysis also showed that high pCONUT scores increased the risk of overall death (hazard ratio: 2.639, 95% confidence interval: 1.365-5.101, P =.004). Conclusions: The pCONUT score is considered a useful prognostic factor in patients with HPC. [ABSTRACT FROM AUTHOR]

Background: Some epithelial tumors express the carbohydrate antigen 125 (Cancer antigen-125, CA-125) and CA 19-9, especially ovarian and pancreatic tumors. Patients with non-Hodgkin lymphoma (NHL) were reported to have a close association between serum CA-125 levels and adverse prognostic factors with worse survival. We aimed to investigate CA-125 and 19-9 expression in nodal diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) tissues using immunohistochemistry (IHC) and their relations to clinicopathological manifestations and patients' survival. Methods: 65 cases of DLBCL NOS were examined. A modified mechanical pencil tip was used to construct Manual Tissue Micro-array (TMA) blocks. Immunohistochemical staining for CA-125 and CA 19-9 was performed and scored semi-quantitatively. All relations were analyzed using established statistical methodologies. Results: Aberrant expression of CA 19-9 was detected in 12% of cases without any expression of CA-125. Moreover, 75% of the CA 19-9 positive cases were statistically significantly associated with anemia and performance status 1. Also, 75% of the CA 19-9 positive cases were females. Conclusions: CA 19-9 was aberrantly expressed in 12% of nodal DLBCL NOS cases and significantly related to anaemia and performance status but not to survival. In cases of DLBCL NOS, CA 19-9 expression cannot be considered an independent prognostic factor. CA-125 was not expressed in nodal DLBCL NOS tissues, necessitating re-evaluation studies. Therefore, it is advised to conduct more research to clarify the potential correlation between serum and tissue CA 19-9 levels and other clinic-pathological characteristics of nodal and extranodal DLBCL NOS patients. [ABSTRACT FROM AUTHOR]

Aims: To assess the impact of the molecular subtype (MS) on the total number of CK19 mRNA copies in all positive SLN (TTL) threshold, to predict non-SLN affectation, and to compare 5 years progression-free survival (PFS) according to the risk of recurrence (ROR) group by PAM50. Methods: Cohort with infiltrating breast cancer with intra-operative metastatic SLN detected by one-step nucleic acid amplification (OSNA) assay who underwent subsequent ALND. Logistic regression was used to assess a possible interaction between TTL and MS(Triple Negative, Her-2-Enriched, Luminal A, or Luminal B), or hormone receptors (HR: positive or negative) by immunohistochemistry (IMH). Cox regression was used to compare PFS and OS in the 3 ROR groups (high, medium, or low). Results: TTL was predictive of non-SLN affectation in both univariate (OR [95% CI]: 1.72 [1.43, 2.05], P <.001) and multivariate (1.55 [95% CI: 1.04, 2.32], P =.030) models, but MS-IMH or HR-IMH, and their interactions with TTL were not (best multivariate model: HR + main effect OR 1.16 [95% CI: 0.18, 7.64], P =.874; interaction OR: 1.04 [0.7, 1.55], P =.835; univariate model: HR + main effect OR: 1.44 [95% CI: 0.85, 2.44], P =.180). PFS was lower in the high-risk ROR group (81.1%) than in the low-risk group (93.9%) (HR: 3.68 [95 CI: 1.70, 7.94], P <.001). Conclusions: our results do not provide evidence to support the utilization of subtype-specific thresholds for TTL values to make therapeutic decisions on the axilla. The ROR group was predictive of 5 years-PFS. [ABSTRACT FROM AUTHOR]

Background: Assessing the prognosis preoperatively in patients with upper tract urothelial carcinoma (UTUC) remains a challenge for urologists. Gross hematuria (GH) and flank pain (FP) are the 2 most common and easily perceived symptoms of UTUC. Therefore, we aimed to investigate the prognostic values of GH and FP in patients with UTUC after undergoing radical nephroureterectomy (RNU). Methods: This article retrospectively analyzed 179 patients with UTUC who underwent RNU and examined the associations between the FP, GH, and long-term survival. After dividing patients into 4 subgroups (presenting as GH without FP, FP without GH, no FP and GH, FP with GH), we focused on the prognostic values of the 4 subgroups using univariate and multivariate analyses. We then proposed a risk stratification model for UTUC based on the independent prognostic factors for cancer-specific survival (CSS) with external validation (146 additional UTUC patients formed the validation cohort). Results: Patients with FP had worse oncological outcomes than those without FP (P <.05). After dividing the 179 patients into 4 subgroups, the "FP without GH" subgroup suffered the worst oncological outcomes (P <.001). The Cox multivariate regression analysis showed that "FP without GH" (P <.001), tumor multifocality (P =.005), and pathological stage (P =.004) were independent prognostic factors for CSS. Good performance of the risk stratification model was achieved in both the training and external validation cohorts. Conclusion: The presence of "flank pain without gross hematuria" was one of the independent risk factors of CSS and OS besides the pathological stage and tumor multifocality. To our knowledge, this is the first study that adding complaint to risk stratification model in UTUC. [ABSTRACT FROM AUTHOR]

BACKGROUND: The influence of the breast as the primary site on the outcome of diffuse large B-cell lymphoma (DLBCL) and further changes in therapeutic strategies remain unclear. We aimed to compare the outcomes between primary breast and non-breast DLBCL and analyze the genetic profiles of some of the study cohorts using next-generation sequencing. METHODS: This matched-pair study reviewed the medical records of 19 patients with stage I and II primary breast DLBCL diagnosed between January 2005 and December 2021 on the basis of the Wiseman and Liao criteria, and we used 1:4 propensity score matching to identify patients with non-breast DLBCL as the control group. The overall response rate, progression-free survival (PFS), and overall survival (OS) were the outcome measures. RESULTS: Patients with primary breast and non-breast DLBCL had a 5-year PFS of 72.6% and 86.9%, respectively (P = .206). These 2 groups also had comparable 5-year OS (86.9% vs 87.8%; P = .772). The breast as the primary site was not associated with inferior PFS (hazard ratio [HR]: 2.14; 95% CI: 0.66-6.96; P = .206) and OS (HR: 1.26; 95% CI: 0.27-5.93; P = .772). CONCLUSION: Patients with primary breast DLBCL and those with non-breast DLBCL had comparable PFS and OS under rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens. Further investigations of the mutation profile, its clinical impact, potential central nervous system relapse, and prognosis of primary breast DLBCL are required. [ABSTRACT FROM AUTHOR]

BACKGROUND: Risk stratification of patients with cervical cancer accompanied by positive lymph nodes (stage IIIC) (the 2018 International Federation of Gynecology and Obstetrics [FIGO] new staging system) yields a clinically heterogeneous group. In this study, we investigated the prognostic performance of the 2018 FIGO staging system for stage IIIC cervical cancer. METHODS: The study included patients with stage III cervical cancer based on the 2018 FIGO staging system, who visited Chongqing University Cancer Hospital between January 2011 and December 2014. Kaplan-Meier curves were generated to evaluate overall survival (OS), which was compared using the log-rank test. The Cox proportional hazard regression model was used for multivariable analysis. RESULTS: A total of 418 patients were eligible for analysis. The 5-year OS was 54.1% for stage IIIC1, 43.3% for stage IIIA, 40.6% for stage IIIB, and 23.1% for stage IIIC2 (P < .001). Multivariable analysis revealed that compared with stages IIIA (hazard ratio [HR] 1.432, 95% con- fidence interval [CI] 0.867-2.366, P = .161) and IIIB (HR 1.261, 95% CI 0.871-1.827, P = .219), stage IIIC1 cancer was not significantly associated with an increased mortality risk. Stage IIIC2 was independently associated with an increased mortality risk compared with stages IIIA (HR 2.958, 95% CI 1.757-4.983, P < .001) and IIIB (HR 2.606, 95% CI 1.752-3.877, P < .001). We stratified patients with stage IIIC1 based on the T stage. The 5-year OS was significantly longer in patients with stage IIIC1 (T1) than in those with stage IIIA (P = .004) or IIIB (P < .001). Analysis of multiple factors revealed that the mortality risk was 2.75-fold higher in patients with stage IIIC1pN>2 than in patients with stage IIIC1pN1-2 (HR 2.753, 95% CI 1.527-4.965, P = .001). CONCLUSIONS: Patients with stage IIIC1 cervical cancer showed heterogeneous clinical characteristics that reflected variable prognoses, depending on the T stage and the extent of pelvic lymph node metastases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nicotinamide N-methyltransferase (NNMT) and Dickkopf-1 (DKK1) play an important role in the development of breast cancer, and the purpose of this study was designed to examine the clinical and prognostic significance of NNMT and DKK1 in breast cancer. METHODS: The GEPIA2 database was used to evaluate the expression and survival of NNMT mRNA and DKK1 mRNA of breast cancer. Then an immunohistochemical study was carried out on 374 cases of breast tissue to identify the protein expression and significance of NNMT and DKK1. Next, the prognostic significance of DKK1 in breast cancer was explored by COX and Kaplan-Meier models. RESULTS: Protein NNMT expression was correlated with lymph node metastasis and histological grade (P < .05) while protein DKK1 expression was related to tumor size, pT stage, histological grade, and Ki-67 (P < .05). Protein DKK1 was related to disease-specific survival (DSS), and low DKK1 expression indicated a poor prognosis of breast cancer patients (P < .05). Combined expression of protein NNMT and protein DKK1 predicted different prognosis of DSS (P < .05). CONCLUSIONS: Nicotinamide N-methyltransferase and DKK1 were linked to breast cancer malignancy and invasion. Breast cancer patients with low DKK1 expression had a worse prognosis. Oncotypes of NNMT and DKK1 expression predicted patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Though the development of targeted cancer drugs continues to accelerate, doctors still lack reliable methods for predicting patient response to standard-of-care therapies for most cancers. DNA methylation has been implicated in tumor drug response and is a promising source of predictive biomarkers of drug efficacy, yet the relationship between drug efficacy and DNA methylation remains largely unexplored. Method: In this analysis, we performed log-rank survival analyses on patients grouped by cancer and drug exposure to find CpG sites where binary methylation status is associated with differential survival in patients treated with a specific drug but not in patients with the same cancer who were not exposed to that drug. We also clustered these drug-specific CpG sites based on co-methylation among patients to identify broader methylation patterns that may be related to drug efficacy, which we investigated for transcription factor binding site enrichment using gene set enrichment analysis. Results: We identified CpG sites that were drug-specific predictors of survival in 38 cancer-drug patient groups across 15 cancers and 20 drugs. These included 11 CpG sites with similar drug-specific survival effects in multiple cancers. We also identified 76 clusters of CpG sites with stronger associations with patient drug response, many of which contained CpG sites in gene promoters containing transcription factor binding sites. Conclusion: These findings are promising biomarkers of drug response for a variety of drugs and contribute to our understanding of drug-methylation interactions in cancer. Investigation and validation of these results could lead to the development of targeted co-therapies aimed at manipulating methylation in order to improve efficacy of commonly used therapies and could improve patient survival and quality of life by furthering the effort toward drug response prediction. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate cell and biochemical biomarkers and establish their prognostic value in patients with advanced laryngeal cancer. Material and Methods: A prospective study included 52 patients with advanced laryngeal carcinoma surgically treated at the tertiary referral center. Tumor tissue was immunohistochemically stained for T-cell markers (CD4 and CD8), and levels of cytokines (IL-6 and IL-8) and C-reactive protein were analyzed from blood samples. Results: Overall 3-year survival (OS) of patients included in the study was 69.2% and the disease specific survival (DSS) 72.5%. Higher expression of CD4+ and CD8+ were significant prognostic factors with positive impact on both OS and DSS in univariate analysis, but not in multivariate analysis. Levels of IL-8 were a significant predictor of 3-year OS and DSS survival in patients with advanced laryngeal cancer but not levels of IL-6 and CRP values. Conclusion: Though high expression of CD4 and CD8 were demonstrated in the tumor tissue, but their prognostic role was not established. Higher values of IL-8 proved to be significant negative predictor of DSS. This could further collaborate the inclusion of combination of biomarkers in assessment of favorable treatment choice in patients with advanced laryngeal carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Oral squamous cell carcinoma (OSCC) is one of the highest-ranking cancers among both genders in Pakistan. Obesity is linked to a much higher risk for developing multiple cancer types. Individuals with Diabetes mellitus (DM) face an increased risk for developing oral cancer. Hence, the objective of this study was to identify the effect of obesity and DM on the prognosis of OSCC patients. Methods: This retrospective cohort analysis was conducted on 386 patients diagnosed and treated for OSCC at The Aga Khan University Hospital, Karachi, Pakistan. Patient information was obtained from hospital medical records. Obesity was defined as having a body mass index (BMI) of ⩾25 kg/m2 according to the WHO Asian cut-offs for BMI. Patient BMI was correlated with diabetes status, clinicopathological features and overall survival. Kaplan-Meier survival analysis was performed, along with univariate and multivariate cox regression analysis to test the effect of obesity and diabetes on overall survival. Results: In a set of 386 patients, there were 296 males (76.7%) and 90 females (23.3%). The mean BMI was 24.4 (SD ± 5.25) and 42.7% of patients were found to be obese (⩾25 BMI). 64 patients (16.6%) were diabetic. The risk of death was significantly higher in underweight patients (P =.035) compared with normal weight individuals. Diabetics had a higher mean BMI compared with non-diabetics. However, DM was not a statistically valid predictor of survival. Conclusion: Underweight OSCC patients were at a higher risk of death compared with normal weight OSCC patients. [ABSTRACT FROM AUTHOR]

Background: Preoperative serum albumin (ALB) and carcinoembryonic antigen (CEA) were useful prognostic factors in colorectal cancer (CRC); however, the ALB to CEA ratio (ACR) and their individual prognostic efficacies have been less studied. Methods: A retrospective study with 156 CRC patients staged I to IV was performed. The prognostic efficacy of ACR was estimated and subsequently compared with ALB, CEA, and other systemic inflammation markers, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR). Differences in progression-free survival (PFS) and overall survival (OS) were determined by Kaplan–Meier (K-M) analysis, and the risk factors for survival were calculated by the Cox proportional hazards model. Results: A total of 31.41% (49 of 156) of patients presented with ACR-low disease, and these patients had tumors with advanced T stages, larger tumor diameters and distant metastases, and a lower LMR. When 5.98 was used as the cut-off point, it had a sensitivity of 58.50% and 61.50% and a specificity of 83.50% and 80.50% for PFS and OS, respectively. ACR displayed a superior prognostic efficacy than individual ALB, CEA and NLR, LMR, and PLR for both PFS and OS (except LMR). Patients in the ACR-low group displayed significantly worse PFS and OS than those in the ACR-high group. Finally, ACR was an independent prognostic factor for both PFS (HR = 0.31, 95% CI: 0.17−0.56, P <.01) and OS (HR = 0.33, 95% CI: 0.16−0.66, P <.01). Conclusions: ACR was a robust prognostic factor in CRC, and patients with a relatively low preoperative ACR would have significantly worse survival. [ABSTRACT FROM AUTHOR]

Worldwide breast cancer ranks first in mortality and incidence rates in women over 20 years old. Rather than one disease, breast cancer is a heterogeneous group of diseases that express distinct molecular profiles. Neoadjuvant chemotherapy is an important therapeutic strategy for breast cancer patients independently of their molecular subtype, with the drawback of resistance development. In addition, chemotherapy has adverse effects that combined with resistance could contribute to lower overall survival. Although great efforts have been made to find diagnostic and prognostic biomarkers for breast cancer and for response to targeted and immune therapy for this pathology, little has been explored regarding biomarkers of response to anthracyclines and taxanes based neoadjuvant chemotherapy. This work aimed to evaluate the molecular profile of patients who received neoadjuvant chemotherapy to identify differentially expressed genes (DEGs) that could be used as biomarkers of chemotherapy response and overall survival. Breast cancer patients who were candidates for neoadjuvant chemotherapy were enrolled in this study. After treatment and according to their pathological response, they were assigned as sensitive or resistant. To evaluate DEGs, Gene Ontology, Kyoto Encyclopedia Gene and Genome (KEGG), and protein–protein interactions, RNA-seq information from all patients was obtained by next-generation sequencing. A total of 1985 DEGs were found, and KEGG analysis indicated a great number of DEGs in metabolic pathways, pathways in cancer, cytokine–cytokine receptor interactions, and neuroactive ligand-receptor interactions. A selection of 73 DEGs was used further for an analysis of overall survival using the METABRIC study and the ductal carcinoma dataset of The Cancer Genome Atlas (TCGA) database. Nine DEGs correlated with overall survival, of which the subexpression of C1QTNF3, CTF1, OLFML3, PLA2R1, PODN, KRT15, HLA-A, and the overexpression of TUBB and TCP1 were found in resistant patients and related to patients with lower overall survival. [ABSTRACT FROM AUTHOR]

BACKGROUND: Assessing the prognosis preoperatively in patients with upper tract urothelial carcinoma (UTUC) remains a challenge for urologists. Gross hematuria (GH) and flank pain (FP) are the 2 most common and easily perceived symptoms of UTUC. Therefore, we aimed to investigate the prognostic values of GH and FP in patients with UTUC after undergoing radical nephroureterectomy (RNU). METHODS: This article retrospectively analyzed 179 patients with UTUC who underwent RNU and examined the associations between the FP, GH, and long-term survival. After dividing patients into 4 subgroups (presenting as GH without FP, FP without GH, no FP and GH, FP with GH), we focused on the prognostic values of the 4 subgroups using univariate and multivariate analyses. We then proposed a risk stratifica- tion model for UTUC based on the independent prognostic factors for cancer-specific survival (CSS) with external validation (146 additional UTUC patients formed the validation cohort). RESULTS: Patients with FP had worse oncological outcomes than those without FP (P < .05). After dividing the 179 patients into 4 sub- groups, the "FP without GH" subgroup suffered the worst oncological outcomes (P < .001). The Cox multivariate regression analysis showed that "FP without GH" (P < .001), tumor multifocality (P = .005), and pathological stage (P = .004) were independent prognostic factors for CSS. Good performance of the risk stratification model was achieved in both the training and external validation cohorts. CONCLUSION: The presence of "flank pain without gross hematuria" was one of the independent risk factors of CSS and OS besides the pathological stage and tumor multifocality. To our knowledge, this is the first study that adding complaint to risk stratification model in UTUC. [ABSTRACT FROM AUTHOR]

Context: The prevalence of venous thromboembolism (VTE) in patients with cancer is particularly high at disease progression and during relapse. Patients cared for in specialized palliative care units (SPCU) are rarely included in VTE studies. Objective: We sought to study the prevalence, clinical characteristics, and survival of individuals with VTE in an SPCU setting. Methods: We retrospectively included 2707 consecutive individuals with active cancer managed at a SPCU. Data were summarized using descriptive statistics and frequency for categorical variables. Overall survival was estimated by Kaplan-Meier and comparisons by log-rank test. Thrombotic events were confirmed by imaging. Results: We studied 1984(73.3%) women and 723 (26.7%) men. The overall prevalence of thrombosis was 22.2% with only 6.2% occurring after initiating SPCU care, and was higher in women (24.6% vs 15.8%), particularly with gynecological tumors (cervical: 30.5%, ovarian: 29.2%). Median survival was slightly longer for patients without VTE (80 days [IQR21-334] and 69 days [IQR 25-235]; p = 0.03). Conclusions: Prevalence of VTE was high and varied by tumor origin. VTE may impact survival. Though median survival is short, some patients are followed over months, suggesting that in the absence of high bleeding risk, treatment for thrombosis in an attempt to decrease the morbidity of re-thrombosis should be considered. On the other hand, few patients developed symptomatic VTE during SPCU care, making generalized primary prophylaxis probably unwarranted. Customizing anticoagulation for the risk of hemorrhage and physical performance is essential. [ABSTRACT FROM AUTHOR]

This study evaluates the prognostic role of carbohydrate antigen 19 to 9 (CA19-9) in predicting survival of pancreatic cancer patients. Literature search was conducted in electronic databases (Google Scholar, Ovid, PubMed, and Science Direct) and study selection was based on precise eligibility criteria. Random-effects meta-analyses were performed to achieve overall estimates of median survival and hazard ratios (HRs) of survival with cutoff defined lower and higher CA19-9 levels before and after surgery or chemotherapy (CT)/radiotherapy (RT) and the changes in CA19-9 levels after any treatment. A total of 41 studies (6519 patients; 42% females; age 63.3 years [95% confidence interval [CI]: 62.2, 64.4]) were included. A pooled HR of 1.79 with a narrow 95% CI (1.58, 2.01) showed that higher CA19-9 levels or less decrease in CA19-9 levels after treatment predicted shorter survival. Median survival in patients with lower and higher preoperative CA19-9 levels was 23.2 months [95% CI: 17.2, 29.2] and 14.0 months [95% CI: 10.9, 17.2], respectively, whereas median survival with lower and higher postoperative CA19-9 levels was 25.0 months [95% CI: 21.9, 28.0] and 13.0 months [95% CI: 10.9, 15.0] respectively. Median survival with lower and higher pre-CT/RT CA19-9 levels was 11.9 months [95% CI: 10.2, 13.6] and 7.7 months [95% CI: 6.2, 9.2], respectively, whereas median survival with lower and higher post-CT/RT CA19-9 levels was 15.1 months [95% CI: 13.2, 17.0] and 10.7 months [95% CI: 7.3, 14.0] respectively. A decrease in CA19-9 levels after treatment was also associated with longer survival. Thus, both pretreatment and posttreatment CA19-9 levels or their changes after treatment have good prognostic value in determining the survival of pancreatic cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Various adjuvant chemotherapies have been introduced for gastric cancer patients after gastrectomy with D2 lymph node dissection. Although the mainstream regimen of adjuvant chemotherapy in Korea includes S-1 monotherapy (TS-1) and capecitabine with oxaliplatin (XELOX), few studies have compared the long-term efficacies of these 2 regimens. Methods: Between January 2010 and June 2017, 2021 patients were diagnosed with gastric cancer and underwent curative resection with adjuvant chemotherapy at our institution. Of 1461 patients with stage IB-III gastric cancer, 825 received TS-1 and 636 received XELOX as adjuvant chemotherapy. We retrospectively reviewed their medical records and analyzed the postoperative 5-year overall survival (OS) and disease-free survival (DFS) of these 2 groups. Results: The patients in the XELOX group had more advanced stage of cancer than the TS-1 group (stages III and II: 56.6% and 43.1%, respectively, in XELOX and 35.3% and 57.0% in TS-1; P <.001). The DFS did not differ significantly between the 2 study groups at any pathologic stage. The OS differed significantly only at pathologic stages IIA (P =.024) and IIB (P =.015). In a multivariate analysis of stage II patients, type of regimen was an independent prognostic factor of OS (XELOX vs TS-1; hazard ratio: 0.47, 95% confidence interval: 0.25-0.89, P =.021). Conclusion: There were similar long-term efficacies between these 2 regimens in advanced gastric cancer patients who underwent curative surgery. However, the XELOX regimen might be favorable for OS of stage II patients. [ABSTRACT FROM AUTHOR]

Background: The systemic inflammation response index (SIRI), a novel and cost-effective serum biomarker, is associated with prognosis in patients with cancer. However, the prognostic value of the SIRI in cancer remains unclear. This study aimed to evaluate the potential role of the SIRI as a prognostic indicator in cancer. Methods: Reports in which the prognostic value of the SIRI in cancer was evaluated were retrieved from electronic databases. The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to evaluate the prognostic significance of the SIRI. The odds ratio (OR) was also calculated to explore the association between the SIRI and clinicopathological features. Results: This study included 30 retrospective studies with 38 cohorts and 10 754 cases. The meta-analysis indicated that a high SIRI was associated with short overall survival (OS) (HR = 2.04, 95% CI = 1.82–2.29, P <.001) and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS) (HR = 2.08, 95% CI = 1.84–2.34, P <.001). Subgroup analysis showed that the prognostic value of the SIRI was significant in all kinds of cancer included. Moreover, the SIRI was significantly correlated with sex, tumor size, T stage, N stage, TNM stage, and lymphovascular invasion. Conclusion: The pretreatment SIRI could be a promising universal prognostic indicator in cancer. [ABSTRACT FROM AUTHOR]

Background: The mortality and recurrence of patients with cancer is of high prevalence. SET-binding factor 2 (SBF2) antisense RNA1 (lncRNA-SBF2-AS1) is a promising long non-coding RNA. There is increasing evidence that SBF2-AS1 is abnormally expressed in various tumors and is associated with cancer prognosis. However, the identification of the effect of lncRNA SBF2-AS1 in tumors remains necessary. Materials and Methods: Up to November 2, 2020, electronic databases, including PubMed, Cochrane Library, EMBASE, Medline, and Web of Science, were searched. The results were evaluated by pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs). Results: A total of 11 literatures on cancer patients were included for the present meta-analysis. The combined results revealed that high expression of SBF2-AS1 was significantly associated with unfavorable overall survival (OS) (HR = 1.48, 95% CI: 1.34-1.62, P < 0.00001) in a variety of cancers. In additional, the increase in SBF2-AS1 expression was also correlated with tumor size ((larger vs. smaller) OR = 2.34, 95% CI: 1.47-3.70, P = 0.0003), advanced TNM stage ((III/IV vs. I/II) OR = 2.78, 95% CI: 1.75-4.41, P < 0.0001), lymph node metastasis ((Positive vs. Negative) OR = 3.06, 95% CI: 1.93-4.86, P < 0.00001), and histological grade ((poorly vs. well/moderately) OR = 2.58, 95% CI: 1.47-4.52, P = 0.001) in patients with cancer. Furthermore, The Cancer Genome Atlas (TCGA) dataset valuated that SBF2-AS1 was upregulated in a variety of tumors, and predicted the worse prognosis. Conclusions: Our results of this meta-analysis demonstrate that high SBF2-AS1 expression may become a potential target for predicting the prognosis of human cancers. [ABSTRACT FROM AUTHOR]