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Background: Altered body composition has been attributed to major health problems globally, particularly in patients with cancer. To date, there have not been sufficient indices for body compositions in predicting the survival of locally advanced breast cancer (LABC). Purpose: To assess the association between body composition and overall survival (OS) as well as disease-free survival (DFS) in patients with LABC. Material and Methods: A retrospective study was conducted of patients with LABC diagnosed between 2010 and 2018. Body composition parameters, including skeletal muscle and adiposity parameters, were measured using computed tomography at the L3 vertebra using in-house software developed by MATLAB and freeware Python 3.6.13. The association between body composition and OS and DFS were analyzed using a log-rank test and multivariate Cox-proportional hazard regression. Results: Of 199 patients, 72 (36%) died during the follow-up period (range = 3.8–150.7 months). Median survival was 101 months. Low visceral-to-subcutaneous ratio ≤0.3 (adjusted hazard ratio [aHR] = 2.57, 95% confidence interval [CI] = 1.51−4.37; aHR = 2.46, 95% CI = 1.33−4.56), and high composite fat (aHR = 3.26, 95% CI = 1.69−6.29; aHR = 2.19, 95% CI = 1.11−4.3) were associated with lower OS and DFS. Positive lymph nodes ≥3, progesterone receptor negative, and total radiation dose >5000 cGy significantly decreased both OS and DFS. A history of previous treatment before body composition assessment and surgery had a protective effect on OS and DFS. No association of sarcopenia, body mass index, and adiposity areas with survival outcomes was observed. Conclusion: Low visceral-to-subcutaneous ratio and high composite fat were independent prognostic factors for OS and DFS in patients with LABC. However, other body composition parameters showed no effect on survival. [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: Intrathecal Drug Delivery Systems (IDDS) are underused in the management of cancer-related pain despite evidence of both efficacy and survival benefit. There is currently limited evidence to indicate which patients might benefit most from IDDS. Aim: The aim of the study was to describe the baseline characteristics and survival outcomes of patients who accepted IDDS, patients who declined IDDS and patients who wished to go ahead with IDDS but whose condition deteriorated before they could do so. Design/participants: The survival data for 75 consecutive patients who had been offered intrathecal drug delivery were examined as part of a retrospective cohort study. Survival data was compared between three groups: those who accepted intrathecal drug delivery and went on to receive it (n = 41), those who accepted it but whose condition deteriorated before it commenced (n = 17) and those who declined this treatment modality (n = 17). Results: Patients who received IDDS survived significantly longer after assessment compared to those who declined IDDS (hazard ratio (HR) for the IDDS group relative to the declined group 0.29 (95% CI 0.16 to 0.53), and 0.23 (95% CI 0.12 to 0.44) after adjustment for gender and baseline functional status. In patients who accepted IDDS but who were unable to commence treatment, survival after assessment was not significantly different from those who declined the IDDS (HR for the deteriorated group relative to the declined group 1.28 (95% CI 0.65 to 2.53), and 0.80 (95% CI 0.65 to 2.53) after adjustment for gender and baseline functional status). Conclusion: In this retrospective analysis, an improvement in survival may be associated with patients who accept ongoing pain management with an implanted intrathecal drug delivery system compared to those patients who either declined intrathecal drug delivery or deteriorated before it could be commenced. [ABSTRACT FROM AUTHOR]

Objective: Multiple myeloma cells resist standard therapies due to overexpression of the transport protein, exportin 1. Selinexor is a novel drug that targets the Exportin 1 protein in these cells. Data source: A comprehensive search was done, and data showing the efficacy and safety of selinexor in relapsed/refractory multiple myeloma was collected using PubMed, Google Scholar, and clincialtrials.gov. Data summary: Results from the clinical trials STORM, BOSTON, and STOMP were included. Parts I and II of the STORM trial revealed a progression-free survival (PFS) of 4.7 and 3.7 months, a median duration of response of 6.2 and 4.4 months, and an overall survival of 7.3 and 8.4 months, respectively. BOSTON trial's SVd arm (selinexor, bortezomib, and dexamethasone) had a median follow-up period of 13.2 months and an mPFS of 13.93 months. The Vd arm (bortezomib and dexamethasone) had a median follow-up duration of 16.5 months and an mPFS of 9.46 months. The STOMP trial is still active and has limited data available. The SKd arm (selinexor, carfilzomib, and dexamethasone) reported an overall response rate of 66.7% in patients with triple refractory multiple myeloma, and 82% in patients with high-risk cytogenetics. The SPd arm (selinexor, pomalidomide, and dexamethasone) shows an overall response rate of 54.30% in pomalidomide naïve-nonrefractory, 35.70% in pomalidomide refractory and 60% in those dosed at RP2D. SRd arm (selinexor, lenalidomide, and dexamethasone) shows an overall response rate of 91.7% in lenalidomide naïve and 12.5% in lenalidomide refractory patients. SVd (selinexor, bortezomib, and dexamethasone) arm reported an overall response rate of 63% in all patients while the SDd arm (selinexor, daratumumab, and dexamethasone) showed an overall response rate of 73%. Conclusion: To improve the outcome of patients with relapsed/refractory multiple myeloma, it is critical to develop new therapies, assess potential therapeutic synergies, and overcome drug resistance by determining the efficacy of multiple myeloma therapies across multiple disease subgroups. [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: The impact of postoperative complications (POCs) classified by the Clavien-Dindo (C-D) system on long-term survival after radical resection in patients with advanced gastric cancer (AGC) is not yet clear. Methods: This study analyzed 531 patients with AGC who underwent radical resection in an institution between January 2015 and December 2017. Patients were divided into 2 groups according to the occurrence of POCs and recorded according to C-D classifications. The long-term survival outcomes of the entire cohort after propensity score matching (PSM) were compared. Results: After PSM, there was no significant difference in baseline data between the complications (C) group (n = 92) and the non-complications (NC) group (n = 92). Survival analysis showed that the 5-year overall survival (OS) and relapse-free survival (RFS) were lower in the C group (48.9% vs 62.0%, P =.040; 38.5% vs 54.9%, P =.005; respectively). Subgroup analysis showed that severe complications (C-D grade > II) were associated with a decrease in 5-year OS and RFS compared with the matched NC group (40.0% vs 62.0%, P =.008; 29.4% vs 54.9%, P =.001; respectively). Multivariate analysis confirmed adjuvant chemotherapy, tumor size, and complications were independent risk factors for poor survival outcomes. Further multivariate analysis showed that older age, combined excision, and comorbidities were independent risk factors for POCs. Conclusions: Severe complications reduced the survival outcome of patients. More attention should be paid to perioperative management of patients with high risk factors for complications. [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 management of locally advanced recurrent nasopharyngeal carcinoma (rNPC) is challenging. The objective of our study was to compare salvage endoscopic nasopharyngectomy (ENPG) with intensity-modulated radiotherapy (IMRT) in clinical outcomes and complications of locally advanced rNPC. Methods: Patients with histologically confirmed rNPC in rT3-4N0-3M0 stages were retrospectively enrolled between January 2013 and December 2019 in this multicenter, case-matched study. The baseline clinicopathological characteristics of patients were balanced by propensity score matching between the ENPG and IMRT groups. ENPG was performed in patients with easily or potentially resectable tumors. The oncological outcomes as well as treatment-related complications were compared between two groups. Results: A total of 176 patients were enrolled and 106 patients were matched. The ENPG group (n = 53) and the IMRT group (n = 53) showed comparable outcomes in the 3-year overall survival rate (68.4% vs. 65.4%, P = 0.401), cancer-specific survival rate (80.9% vs. 74.4%, P = 0.076), locoregional failure-free survival rate (36.6% vs. 45.3%, P = 0.076), and progression-free survival rate (27.5% vs. 32.3%, P = 0.216). The incidence of severe treatment-related complications of patients in the ENPG group was lower than that in the IMRT group (37.7% vs. 67.9%, P = 0.002). The most common complications were post perioperative hemorrhage (13.2%) in ENPG group and temporal lobe necrosis (47.2%) in IMRT group, respectively. Conclusion: Salvage ENPG exhibits comparable efficacy but less toxicities than IMRT in carefully screened patients with locally advanced rNPC, which may be a new choice of local treatment. [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]

Introduction: Retrospective studies have suggested that patients with poor performance status treated with immune checkpoint inhibitors have shorter overall survival and poorer response rates. This study was undertaken to investigate the possible relationships between inpatient immune checkpoint inhibitor use and clinical outcomes. Methods: This was a retrospective chart review of cancer patients who received an immune checkpoint inhibitor while hospitalized from 1 January 2016 to 30 December 2020. The primary outcome was 90-day mortality or admission to hospice rate. Secondary outcomes included overall survival, time to death or discharge to hospice, and descriptive summarization of patient characteristics. Results: A total of 52 patients were analyzed. At 90 days, 68.2% of subjects were expired or admitted to hospice (95% CI: 54.7–81%). 90-day overall survival was 47.1%; median survival time was 81 days (95% CI: 28–242 days). The median time to death or hospice was 35 days (95% CI: 24–72 days). The time to death or hospice was shorter for immune checkpoint inhibitor-naive patients compared to those who received immune checkpoint inhibitors prior to admission (29 days, 95% CI: 12–43 days vs. 242 days, 95% CI: 36–1288 days, respectively; HR: 2.74, 95% CI: 1.2–6.25; p = 0.0121). No differences were found when comparing other baseline characteristics. Conclusion: A majority of patients who received an immune checkpoint inhibitor while hospitalized were either discharged to hospice or expired by 90 days. An increased rate of death or discharge to hospice was observed for patients who were immune checkpoint inhibitor-naive prior to their admission. [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]

Objectives: Hypopharyngeal and laryngeal cancers are aggressive and usually diagnosed at advanced stage with esophagus invasion. Total pharyngolaryngoesophagectomy with gastric pull-up reconstruction has been a common surgery for these cancers but long-term outcomes are still questionable. This study aimed to investigate short-term and long-term outcomes of patients who underwent this surgery. Methods: Patients with hypopharyngeal or laryngeal cancer invading cervical esophagus who underwent total pharyngolaryngoesphagectomy with gastric pull-up between 2012 and 2016 was included and followed up until 2021. Short-term outcomes were complications and long-term outcomes were overall survival (OS) and disease-free survival (DFS). Results: Fifty patients were included with a mean age of 60.3 years and 94% were male. Pyriform fossa was the most common primary site of tumor (50%), followed by posterior hypopharyngeal wall (18%) and postcricoid region (18%). Mean operating time, postoperative oral intake and hospital stay was 363.1 ± 43.6 minutes, 8.8 ± 3.6 days and 14.2 ± 3.0 days respectively. Complications occurred in 15 patients (30%) without any in-hospital death. During the follow-up period, 17 patients had recurrence and 35 patients died. Median (95% confidence interval [CI]) OS and DFS time were 30 (21-37) and 30 (19-36) months. Five-year OS and DFS probability (95% CI) were 22.6% (12.8-39.7) and 22.7% (12.9-39.8). Conclusions: Total pharyngolaryngoesophagectomy with gastric pull-up is feasible and safe. However, even with curative surgery and multimodal treatment, advanced pharyngeal or laryngeal cancer with cervical esophagus invasion still has poor survival outcome. [ABSTRACT FROM AUTHOR]

Daratumumab is the first anti-CD38 targeting monoclonal antibody approved as monotherapy in multiply relapsed myeloma patients who progressed following prior treatment with proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). We present real world data on the efficacy of single agent daratumumab in a cohort of 55 multiply relapsed patients treated in the UK. The median age was 72 years, the majority (96%) received ≥ 3 previous lines of treatment; 54.5% were PI-refractory, 76.4% were IMiD-refractory and 47.2% were double refractory; 20% of patients had high-risk (HR) disease. The overall response rate was 49%. After a median follow up of 9.2 months, the median progression-free survival (PFS) for the total cohort was 5.1 months. Patients who achieved a partial response or better (≥PR) demonstrated a significantly longer PFS compared to those with

Purpose: No large-scale prospective randomized study with a long-term follow-up period has evaluated the survival outcomes of preconcurrent chemoradiotherapy (CCRT) 18-fluorodeoxyglucose positron emission tomography–computed tomography (18FDG PET–CT) in patients with non–human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Patients and Methods: We included patients with stage I–IVA p16-negative OPSCC receiving definitive CCRT and categorized them into two groups according to pre-CCRT 18FDG PET–CT and compared their outcomes: the case group consisted of patients who underwent pre-CCRT 18FDG PET–CT, whereas the comparison group consisted of patients who did not receive pre-CCRT 18FDG PET–CT. Results: The final cohort consisted of 3942 patients (1663 and 2279 in the case and comparison groups, respectively). According to multivariable Cox regression analysis, pre-CCRT 18FDG PET–CT was not a significant prognostic factor for overall survival in patients with stages I–II of p16-negative OPSCC receiving standard CCRT. The adjusted hazard ratio (95% confidence interval) of all-cause death for the patients with advanced stages (III–IVA) of p16-negative OPSCC receiving pre-CCRT 18FDG PET–CT was 0.75 (0.87–0.94, P = 0.0236). Conclusions: Routine use of pre-CCRT 18FDG PET–CT is not necessary for each patient with p16-negative OPSCC. Pre-CCRT 18FDG PET–CT is associated with improved survival in patients with stage III–IVA p16-negative OSCC, but might be not in those with stage I–II p16-negative OPSCC. No large-scale prospective randomized study with a long-term follow-up period has evaluated the survival outcomes of preconcurrent chemoradiotherapy (CCRT) 18-fluorodeoxyglucose positron emission tomography–computed tomography (18FDG PET–CT) in patients with p16-negative oropharyngeal squamous cell carcinoma (OPSCC). Our study is the first, largest, homogenous modality study on PET–CT including a long-term follow-up cohort to examine the survival outcomes of pre-CCRT 18FDG PET–CT or non-pre-CCRT PET–CT for patients with p16-negative OPSCC receiving standard CCRT stratified by different clinical stages. Routine use of pre-CCRT 18FDG PET–CT is not necessary for each patient with p16-negative OPSCC. Pre-CCRT 18FDG PET–CT is associated with improved survival in patients with stage III–IVA p16-negative OPSCC, but might be not in those with stage I–II p16-negative OPSCC. [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]

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: 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: 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]

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]

Background: Complete resection is the only potentially curative treatment in patients with pancreatic ductal adenocarcinoma (PDA) and is associated with a longer overall survival (OS) than incomplete resection of tumor. Hence, prediction of the resection status after surgery would help predict the prognosis of patients with PDA. Purpose: To predict residual tumor (R) classification and OS in patients who underwent first-line surgery for PDA using preoperative magnetic resonance imaging (MRI). Material and Methods: In this study, 210 patients with PDA who underwent MRI and first-line surgery were randomly categorized into a test group (n=150) and a validation group (n=60). The R classification was divided into R0 (no residual tumor) and R1/R2 (microscopic/macroscopic residual tumor). Preoperative MRI findings associated with R classification and OS were assessed by using logistic regression and Cox proportional hazard models. In addition, the prediction models for the R classification and OS were validated using calibration plots and C statistics. Results: On preoperative MRI, portal vein encasement (odds ratio 4.755) was an independent predictor for R1/R2 resection (P =0.040). Tumor size measured on MRI (hazard ratio [HR] per centimeter 1.539) was a predictor of OS, along with pathologic N1 and N2 stage (HR 1.944 and 3.243, respectively), R1/R2 resection (HR 3.273), and adjuvant chemoradiation therapy (HR 0.250) (P <0.050). Calibration plots demonstrated satisfactory predictive performance. Conclusion: Preoperative MRI was valuable for predicting R1/R2 resection using portal vein encasement. Tumor size measured on MRI was useful for the prediction of OS after first-line surgery for PDA. [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: 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]

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 RESULTScould 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]

Background: Genetic polymorphism within the P1 isoenzyme of the Glutathione-S-Transferase (GST) family is found to modulate and alter the enzyme activity of GSTP1 protein and thus may result in a change of sensitivity to platinum-based chemotherapy. We investigated the relationship between GSTP1 Ile 105 Val polymorphisms and overall survival, treatment response, and for both hematological and non-hematological toxicity of advanced North Indian lung cancer patients undergoing platinum-based double chemotherapy. Methods: The polymorphism of GSTP1 Ile 105 Val in North Indian lung cancer patients was assessed by polymerase chain reaction-restriction fragment length polymorphism. A total of 682 lung cancer patients were enrolled in the study, and it was observed that patients who were carrying both the mutant alleles (Val/Val) for the GSTP1 polymorphism showed a higher trend of median survival time (MST) as compared to the patients bearing the wild type of genotype (Ile/Ile) (MST = 8.30 vs. 7.47, p = 0.56). Based on toxicity profiling, we observed that lung cancer patients with the mutant genotype of GSTP1 (Val/Val) had an increased risk of leukopenia (OR = 2.41; 95% CI = 1.39-4.18, p = 0.001) as compared to subjects carrying both copies of the wild alleles (Ile/Ile). Our data suggested that patients with heterozygous genotype (Ile/Val) had a 2.14-fold increased risk of developing severe anemia (OR = 2.14, 95% CI = 0.97-4.62, p = 0.03). Our data also showed that in small cell lung carcinoma (SCLC) patients' polymorphism of GSTP1 was associated with thrombocytopenia (χ2 test = 7.32, p = 0.02). Conclusions: Our results suggest that GSTP1 Ile105Val polymorphism could be a predictive biomarker for hematological toxicity, like leukopenia and anemia, but not thrombocytopenia or neutropenia [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]

Objective: Cytokines have been the mainstay of treatment in metastatic renal cell cancer (mRCC) for decades before the introduction of tyrosine kinase inhibitors (TKIs), which dramatically changed the therapeutic landscape in these patients. This observational study was designed to evaluate use of TKIs in the treatment of cytokine-intolerant mRCC patients. Methods: A total of 151 cytokine-intolerant mRCC patients who were treated with TKIs (sunitinib, pazopanib and sorafenib) were enrolled in this prospective, non-interventional, multi-center observational study at 16 oncology centers across Turkey. Mean (SD) age was 61.3 (11.1) years and 74.8% were males. Data on duration of TKI treatment was the primary outcome measure. Additionally, overall response rate (ORR), progression free survival (PFS), overall survival (OS) and safety data were recorded. Results: Median duration of treatment was 8.2 months at a median follow up of 17.9 months. ORR and disease control rate were 12.5% and 70.8%, respectively. Median PFS and OS were 7.5 months (95%CI: 6.4–10.4) and 27.3 months (95%CI: 17.6–27.3) with no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS. The most common adverse events excluding progression-which was the protocol requirement were diarrhea (13.6%), asthenia (13.6%) and hand-foot syndrome (12.6%). Dose modifications were required in 30.5% of the patients and 15% discontinued TKIs because of toxicity. Conclusions: Our findings confirm the efficacy and safety profile of TKIs in the first-line treatment of mRCC patients intolerant to cytokine treatment. There was no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS. Trial registration: TURCOS ClinicalTrials.gov Identifier: NCT01585974. Registered April 25, 2012. [ABSTRACT FROM AUTHOR]