Prognostic Factor For Worse Survival Research Articles

Association of low adherence to weekly cisplatin with outcomes in patients with head and neck squamous cell carcinoma: a retrospective cohort study

BackgroundThe National Comprehensive Cancer Network (NCCN) guideline recommends consideration of weekly cisplatin as an alternative option for patients with head and neck cancer undergoing definitive chemoradiation. However, in a recent phase III trial (ConCERT), 20% of patients treated with weekly cisplatin could not receive a total of 200 mg/m2, and the association of low adherence to weekly cisplatin and cancer control outcomes remains unclear. To fill this knowledge gap, we performed an observational cohort study of patients with head and neck cancer undergoing definitive chemoradiation with weekly cisplatin.MethodsOur institutional database was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation with weekly cisplatin (40 mg/m2) between November 2007 and April 2023. Adherence to weekly cisplatin was defined as receiving at least 5 cycles with a total cumulative dose of 200 mg/m2. Survival outcomes were evaluated using Kaplan–Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Logistic MVA was performed to identify variables associated with low adherence to weekly cisplatin. Fine-Gray MVA was performed to analyze failure outcomes with death as a competing event.ResultsAmong 119 patients who met our criteria, 51 patients (42.9%) had low adherence to weekly cisplatin. Median follow up was 19.8 months (interquartile range 8.8–65.6). Low adherence to weekly cisplatin was associated with worse overall survival (adjusted hazards ratio [aHR] 2.94, 95% confidence interval [CI] 1.58–5.47, p < 0.001) and progression-free survival (aHR 2.32, 95% CI 1.29–4.17, p = 0.005). It was also associated with worse distant failure (aHR 4.55, 95% CI 1.19–17.3, p = 0.03), but not locoregional failure (aHR 1.61, 95% CI 0.46–5.58, p = 0.46). KPS < 90 was the only variable associated with low adherence to weekly cisplatin (adjusted odds ratio [aOR] 2.67, 95% CI 1.10–6.65, p = 0.03).ConclusionOur study suggested that over 40% of patients underwent fewer than 5 weekly cisplatin cycles and that low adherence to weekly cisplatin was an independent, adverse prognostic factor for worse survival and distant failure outcomes. Those with reduced adherence to weekly cisplatin were more likely to have poor performance status. Further studies are warranted to improve the adherence to chemotherapy and outcomes.

The Prognostic Role of Perineural Invasion for Survival in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

The aim of this study was to conduct a comprehensive review of the predictive significance of PNI in HNSCC survival outcomes. A systematic search was conducted across multiple databases, and all studies published in the last decade were screened (Research Registry ID: reviewregistry1853). The included studies were assessed using the Quality in Prognosis Studies tool. Survival outcome data were extracted, combined, and presented as hazard ratios (HR) with a 95% confidence interval (CI). Totally, 74 studies encompassing 27,559 patients were analyzed and revealed a cumulative occurrent rate of 30% for PNI in HNSCC. PNI+ HNSCC patients had a worse overall survival (HR: 1.91, 95% CI: 1.71-2.13), disease-specific survival (HR: 1.79, 95% CI: 1.55-2.07), disease-free survival (HR: 1.82, 95% CI: 1.69-1.96), local recurrence (HR: 2.54, 95% CI: 1.93-3.33), locoregional recurrence (HR: 2.27, 95% CI: 1.82-2.82), locoregional relapse free survival (HR: 1.77, 95% CI: 1.28-2.45), distant metastasis (HR: 1.82, 95% CI: 1.34-2.48), and distant metastasis-free survival (HR: 2.97, 95% CI: 1.82-4.85) compared to those PNI- patients. The available evidence unequivocally establishes PNI as a critical prognostic factor for worse survival in HNSCC patients.

Prognostic model for resected borderline and locally advanced pancreatic cancer after neoadjuvant chemotherapy.

The current AJCC 8th has been reported to have a poor ability to predict the prognosis in patients with resected borderline resectable pancreatic cancer and locally advanced pancreatic cancer following neoadjuvant chemotherapy. This study was aimed to develop an improved prognostic model by incorporating pathology and parameters of biologic response (BR). A retrospective cohort study was conducted including patients who underwent curative-intent surgery following chemotherapy. We developed a modified ypT staging system and incorporated the BR, involving normalization of carbohydrate antigen 19-9 and reduction in the maximum standardized uptake value simultaneously after chemotherapy. The prognostic performance of the current pathologic system, modified pathologic system, and newly developed system incorporating pathology and BR were compared. In this study, 171 patients underwent surgery following chemotherapy. The modified T stage, which unified ypT2 and ypT3, demonstrated improved prognostic performance than the current staging system (area under the curve: 0.706 vs. 0.661). Biologic unresponsiveness was an independent prognostic factor for worse survival (hazard ratio 2.31, 95% confidence interval 1.50-3.55, P<0.001). The modified pathology with BR system demonstrated the highest discriminative ability in predicting 5-year overall survival than the current pathologic system (area under the curve: 0.785 vs. 0.661, P=0.010) and modified pathologic staging system (area under the curve: 0.785 vs. 0.706, P=0.002). The prognostic model, incorporating modified ypT staging and elevated carbohydrate antigen 19-9 levels and maximum standardized uptake value simultaneously, demonstrated improved results in predicting oncologic outcomes for patients who underwent surgery following neoadjuvant chemotherapy.

Metabolic tumor burden as a prognostic indicator after neoadjuvant chemotherapy in pancreatic cancer.

There is no standardized assessment for evaluating response although neoadjuvant chemotherapy (NAT) is widely accepted for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). This study was aimed to evaluate NAT response using positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose ( 18 F-FDG-PET/CT) parameters alongside carbohydrate antigen (CA) 19-9 levels. Patients who underwent surgery after NAT for BRPC and LAPC between 2017 and 2021 were identified. The study assessed the prognostic value of PET-derived parameters after NAT, determining cutoff values using the K-adaptive partitioning method. It created four groups based on the elevation or normalization of PET parameters and CA19-9 levels, comparing survival between these groups. Of 200 eligible patients, FOLFIRINOX and gemcitabine-based NAT were administered in 167 and 34 patients, respectively (mean NAT cycles, 8.3). In a multivariate analysis, metabolic tumor volume (MTV) demonstrated the most robust performance in assessing response (HR 3.11, 95% CI 1.73-5.58, P <0.001) based on cut-off value of 2.4. Patients with decreased MTV had significantly better survival than those with elevated MTV among individuals with CA19-9 levels <37IU/L (median survival; 35.5 vs. 20.9mo, P <0.001) and CA19-9 levels ≥37IU/L (median survival; 34.3 vs. 17.8mo, P =0.03). In patients suspected to be Lewis antigen negative, predictive performance of MTV was found to be limited ( P =0.84). Elevated MTV is an influential prognostic factor for worse survival, regardless of post-NAT CA19-9 levels. These results could be helpful in identifying patients with a poor prognosis despite normalization of CA19-9 levels after NAT.

Association of absolute neutrophil count with outcomes in patients with head and neck cancer treated with chemoradiation.

e18055 Background: Systematic inflammation plays an integral role in tumor development and metastasis. High neutrophil counts, among various peripheral blood biomarkers, have been shown to be associated with worse survival outcomes in multiple cancer types. To evaluate the absolute neutrophil count (ANC) as a prognostic biomarker in head and neck cancer, we performed an observational cohort study of patients undergoing definitive chemoradiation. Methods: Our institutional database at the Roswell Park Comprehensive Cancer Center was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation between June 2007 and April 2023. ANC was analyzed as a continuous variable. Survival outcomes were assessed using Kaplan-Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Fine-Gray MVA was used to analyze failure outcomes with death as a competing event. To reduce selection bias, propensity score matching was performed using ANC as a dichotomous variable with its median value as a cutoff. Subgroup analyses were performed among p16-negative and p16-positive cohorts. Results: A total of 668 patients who met our criteria. Median follow up was 30.3 months (interquartile range 9.9-60.7). Elevated ANC as a continuous variable was associated with worse overall survival (OS; adjusted hazards ratio [aHR] 1.02, 95% confidence interval [CI] 1.01-1.04, p=0.003), progression free survival (PFS; aHR 1.03, 95% CI 1.01-1.04, p&lt;0.001), and distant failure (DF; aHR 1.03, 95% CI 1.01-1.05, p=0.007), but not locoregional failure (LRF; aHR 1.02, 95% CI 1.00-1.05, p=0.10). Similar findings were noted among 278 matched pairs (OS: hazards ratio [HR] 1.66, 95% CI 1.23-2.26, p=0.001; PFS: HR 1.74, 95% CI 1.31-2.29, p&lt;0.001; LRF: HR 1.66, 95% CI 0.98-2.80, p=0.06; DF: HR 1.64, 95% CI 1.03-2.60, p=0.04). On subgroup analysis, among 118 patients with p16-negative tumors, elevated ANC as a continuous variable was not associated with OS (aHR 1.00, 95% CI 0.90-1.11, p=0.97) and PFS (aHR 0.97, 95% CI 0.87-1.08, p=0.54). The number of LRF (n=21) and DF (n=17) were too few to analyze in this subgroup. However, among 344 patients with p16-positive tumors, high ANC was associated with worse OS (aHR 1.03, 95% CI 1.00-1.06, p=0.046), PFS (aHR 1.05, 95% CI 1.02-1.07, p&lt;0.001), LRF (aHR 1.08, 95% CI 1.05-1.12, p&lt;0.001), and DF (aHR 1.04, 95% CI 1.01-1.08, p=0.02). Conclusions: Our study suggested that elevated ANC was an independent, adverse prognostic factor for worse survival and distant metastasis outcomes. Similar findings were also observed among patients with p16-positive tumors, with high ANC also associated with worse locoregional failure. Further studies are warranted to tailor interventions based on such biomarkers.

Association of low adherence to weekly cisplatin with outcomes in patients with head and neck cancer treated with chemoradiation.

e18053 Background: The National Comprehensive Cancer Network (NCCN) guideline recommends consideration of weekly cisplatin as an alternative option for patients with head and neck cancer undergoing definitive chemoradiation. However, in a recent phase III trial (ConCERT), 20% of patients treated with weekly cisplatin could not receive a total of 200 mg/m2, and the association of low adherence to weekly cisplatin and cancer control outcomes remains unclear. To fill this knowledge gap, we performed an observational cohort study of patients with head and neck cancer undergoing definitive chemoradiation with weekly cisplatin. Methods: Our institutional database at the Roswell Park Comprehensive Cancer Center was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation with weekly cisplatin (40 mg/m2) between November 2007 and April 2023. Adherence to weekly cisplatin was defined as receiving at least 5 cycles with a total cumulative dose of 200 mg/m2. Survival outcomes were evaluated using Kaplan-Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Logistic MVA was performed to identify variables associated with low adherence to weekly cisplatin. Fine-Gray MVA was performed to analyze failure outcomes with death as a competing event. Results: Among 119 patients who met our criteria, 51 patients (42.9%) had low adherence to weekly cisplatin. Median follow up was 19.8 months (interquartile range 8.8-65.6). Low adherence to weekly cisplatin was associated with worse overall survival (adjusted hazards ratio [aHR] 2.94, 95% confidence interval [CI] 1.58-5.47, p&lt;0.001) and progression-free survival (aHR 2.32, 95% CI 1.29-4.17, p=0.005). It was also associated with worse distant failure (aHR 4.55, 95% CI 1.19-17.3, p=0.03), but not locoregional failure (aHR 1.61, 95% CI 0.46-5.58, p=0.46). KPS &lt;90 was the only variable associated with low adherence to weekly cisplatin (adjusted odds ratio [aOR] 2.67, 95% CI 1.10-6.65, p=0.03). Conclusions: Our study suggested that over 40% of patients underwent fewer than 5 weekly cisplatin cycles and that low adherence to weekly cisplatin was an independent, adverse prognostic factor for worse survival and distant failure outcomes. Those with reduced adherence to weekly cisplatin were more likely to have poor performance status. Further studies are warranted to improve the adherence to chemotherapy and outcomes.

Prognostic impact of preoperative atrial fibrillation in patients undergoing heart surgery in cardiogenic shock

Surgical intervention in the setting of cardiogenic shock (CS) is burdened with high mortality. Due to acute condition, detailed diagnoses and risk assessment is often precluded. Atrial fibrillation (AF) is a risk factor for perioperative complications and worse survival but little is known about AF patients operated in CS. Current analysis aimed to determine prognostic impact of preoperative AF in patients undergoing heart surgery in CS. We analyzed data from the Polish National Registry of Cardiac Surgery (KROK) Procedures. Between 2012 and 2021, 332,109 patients underwent cardiac surgery in 37 centers; 4852 (1.5%) patients presented with CS. Of those 624 (13%) patients had AF history. Cox proportional hazards models were used for computations. Propensity score (nearest neighbor) matching for the comparison of patients with and without AF was performed. Median follow-up was 4.6 years (max.10.0), mean age was 62 (± 15) years and 68% patients were men. Thirty-day mortality was 36% (1728 patients). The origin of CS included acute myocardial infarction (1751 patients, 36%), acute aortic dissection (1075 patients, 22%) and valvular dysfunction (610 patients, 13%). In an unadjusted analysis, patients with underlying AF had almost 20% higher mortality risk (HR 1.19, 95% CIs 1.06–1.34; P = 0.004). Propensity score matching returned 597 pairs with similar baseline characteristics; AF remained a significant prognostic factor for worse survival (HR 1.19, 95% CI 1.00–1.40; P = 0.045). Among patients with CS referred for cardiac surgery, history of AF was a significant risk factor for mortality. Role of concomitant AF ablation and/or left atrial appendage occlusion or more aggressive perioperative circulatory support should be addressed in the future.

P11.28.ATERT C228T: A NOVEL MOLECULAR INDEPENDENT PROGNOSTIC FACTOR IN PATIENTS WITH GLIOBLASTOMA IDH WILD TYPE

Abstract BACKGROUND TERT promoter (TERTp) variants regulate TERT expression and are the most frequent mutations in glioblastoma (GB), specifically c. -124C&amp;gt;T and c.-146C&amp;gt;T, known as C228T and C250T respectively. The role on prognosis of TERTp mutation is unclear and its clinical impact remains unknown. We assess the association of the status of TERTp considering the mutation subtype (C228T vs C250T vs TERTp wild type (WT)) with outcomes in patients (pts) with GB IDH-WT. MATERIAL AND METHODS We expanded a retrospective multicenter study to include pts with GB treated between 2010-2022 with standard treatment (radiotherapy with concomitant and adjuvant temozolomide). Clinical, molecular, and histological data were collected from medical reports. C228T and C250T TERTp mutations were assesed by PCR/Sanger sequencing (93%) or NGS (7%). MGMTp methylation and IDH mutation were tested by MS-PCR and immunohistochemistry/sequencing, respectively. Median overall survival (mOS) was estimated using the Kaplan-Meier method and compared between strata through the log-rank test. Multivariate Cox regression models were performed to adjust the effect of C228T mutation by MGMTp methylation, age, Karnofsky (KPS) and type of surgery and to assess the potential role of the interaction of both molecular factors RESULTS A total of 255 pts have been enrolled with a median follow up of 14.2 months; 63% were male, 35% older than 65 years old, 70% had a Karnofsky Index &amp;gt;80%, 40% had gross total resection and 51% had MGMTp methylation. A total of 86 pts (34%) were treated with bevacizumab in latter lines.The presence of TERTp mutation C228T was observed in 54.7% (N=140), C250T in 22.7% (N=58) and the rest (N=57) were TERTp WT. The median OS was 16.4 months (95% CI 14.7 - 18). The C250T mutation was significantly associated with better OS 21.7 months (95% CI 16.1 - 32; p=0.041). Multivariate analysis confirmed that C228T TERTp mutation confers worse prognosis independently of methylation status, age, KPS and type of surgery (HR 1.55; 1.07-2.24 p=0.02). In a further multivariate analysis to assess the potential role of the interaction between both molecular factors, pts with GB unmethylated MGMTp/C228T TERTp mutation had the worse prognoses (HR = 2.83, 95% CI: 1.59-5.03, p &amp;lt; 0.001), followed by the unmethylated MGMTp/C250T (HR = 2.06, 95% CI: 1.08 - 3.94, p = 0.028), and methylated MGMTp/C228T TERTp (HR = 1.80, 95% CI: 1.01 - 3.17, p = 0.041). CONCLUSION We report that TERTp C228T mutation is an independent prognostic factor of worse survival regardless of MGMT methylation status, age, KPS and type of surgery, in pts with GB IDH-WT treated homogeneously with standard treatment. We purpose to consider it as an important new prognostic molecular factor in the design of new clinical trials.

Splicing factor TRA2A contributes to esophageal cancer progression via a noncanonical role in lncRNA m6 A methylation.

Transformer 2 alpha homolog (TRA2A), a member of the serine/arginine-rich splicing factor family, has been shown to control mRNA splicing in development and cancers. However, it remains unclear whether TRA2A is involved in lncRNA regulation. In the present study, we found that TRA2A was upregulated and correlated with poor prognosis in esophageal cancer. Downregulation of TRA2A suppressed the tumor growth in xenograft nude mice. Epitranscriptomic microarray showed that depletion of TRA2A affected global lncRNA methylation similarly to the key m6 A methyltransferase, METTL3, by silencing. MeRIP-qPCR, RNA pull-down, CLIP analyses, and stability assays indicated that ablation of TRA2A reduced m6 A-modification of the oncogenic lncRNA MALAT1, thus inducing structural alterations and reduced stability. Furthermore, Co-IP experiments showed TRA2A directly interacted with METTL3 and RBMX, which also affected the writer KIAA1429 expression. Knockdown of TRA2A inhibited cell proliferation in a manner restored by RBMX/KIAA1429 overexpression. Clinically, MALAT1, RBMX, and KIAA1429 were prognostic factors of worse survival in ESCA patients. Structural similarity-based virtual screening in FDA-approved drugs repurposed nebivolol, a β1 -adrenergic receptor antagonist, as a potent compound to suppress the proliferation of esophageal cancer cells. Cellular thermal shift and RIP assay indicated that nebivolol may compete with MALAT1 to bind TRA2A. In conclusion, our study revealed the noncanonical function of TRA2A, which coordinates with multiple methylation proteins to promote oncogenic MALAT1 during ESCA carcinogenesis.

Overexpression of AKR1B10 Predicts Poor Prognosis in Gastric Cancer Patients Undergoing Surgical Resection.

Aldo-keto reductase family 1 member B10 (AKR1B10) is associated with several cancers, but the prognostic role in gastric cancer (GC) remains unclear. We enrolled 359 GC patients who underwent a gastrectomy with D2 lymph node dissection. AKR1B10 expression was scored using an immunoreactive scoring system based on immunohistochemistry. Adjuvant chemotherapy with S-1 or oxaliplatin plus capecitabine was administered to pathological stage II or III disease patients. There were 117 (32.6%) and 242 (67.4%) patients with AKR1B10 overexpression and low expression, respectively. Patients overexpressing AKR1B10 had worse 5-year disease-free survival (DFS) and overall survival (OS) rates than those with low expression of AKR1B10. Pathological T3-T4 stage, pathological stage III, lymph node ratio ≥25%, and AKR1B10 overexpression were independent prognostic factors for worse DFS and OS in univariate and multivariate analyses. For 162 stage II or III patients who received adjuvant chemotherapy after surgical resection and 59 patients with signet ring cell carcinoma histology, AKR1B10 overexpression was also associated with inferior DFS and OS. AKR1B10 was not associated with clinical survival in stage I GC patients. In conclusion, AKR1B10 overexpression may be an independent prognostic factor for worse survival in GC patients who underwent gastrectomy with D2 lymph node dissection.

Significant muscle loss after stereotactic body radiotherapy predicts worse survival in patients with hepatocellular carcinoma

The relationship between sarcopenia and treatment outcomes, especially in patients with hepatocellular carcinoma (HCC) undergoing stereotactic body radiotherapy (SBRT) has not been well-explored. This study aimed to investigate the effects of sarcopenia on the survival and toxicity after SBRT in patients with HCC. We included 137 patients with HCC treated with SBRT between 2008 and 2018. Sarcopenia was defined as a skeletal muscle index (SMI) of < 49 cm2/m2 for men and < 31 cm2/m2 for women using computed tomography images at the mid-level of the third lumbar vertebra. The SMI change was presented as the change per 90 days. The Kaplan–Meier method was used for survival estimation, and the Cox regression was used to determine prognosticators. Sarcopenia was present in 67 of 137 eligible patients. With the median follow-up of 14.1 months and 32.7 months in the entire cohort and in those alive, respectively, patients with pre-SBRT sarcopenia or SMI loss ≥ 7% after SBRT had worse overall survival than their counterparts. Significant survival predictors on multivariate analysis were SMI loss ≥ 7% after SBRT [hazard ratio (HR): 1.96, p = 0.013], presence of extrahepatic metastasis (HR: 3.47, p < 0.001), neutrophil-to-lymphocyte ratio (HR: 1.79, p = 0.027), and multiple tumors (HR: 2.19, p = 0.003). Separate Cox models according to the absence and presence of pre-SBRT sarcopenia showed that SMI loss ≥ 7% remained a significant survival predictor in patients with sarcopenia (HR: 3.06, p = 0.017) compared with those without sarcopenia. SMI loss ≥ 7% is also a predictor of the Child–Pugh score increase by ≥ 2 points after SBRT. SMI loss ≥ 7% after SBRT is a significant prognostic factor for worse survival and is associated with liver toxicity compared with pre-SBRT sarcopenia.

Prognostic significance of YAP1 expression and its association with neuroendocrine markers in resected pulmonary large cell neuroendocrine carcinoma (LCNEC)

BackgroundYAP1 (Yes-associated protein 1), an important effector of the Hippo pathway, acts as an oncogene and is overexpressed in various malignant tumors. However, the function and expression pattern of YAP1 in pulmonary large cell neuroendocrine carcinoma (LCNEC) have not been systematically established. This study aimed to explore the relationship between YAP1 expression and neuroendocrine differentiation markers and their prognostic significance in LCNEC. Materials and methodsYAP1 protein and neuroendocrine markers (INSM1, NeuroD1 and DLL3) expression were examined by immunohistochemical (IHC) staining in 80 resected pulmonary LCNEC cases. The possible association between these markers and clinicopathological features was evaluated and survival analyses were performed. ResultsYAP1 was highly expressed in 25% LCNECs (20/80) , especially at a relatively higher T stage (p = 0.015). YAP1 expression was negatively correlated with INSM1 (χ2=11.53, p = 0.001) and DLL3(χ2=8.55, p = 0.004), but not with NeuroD1 (p = 0.482). For survival analyses, YAP1 expression was associated with worse disease-free survival (DFS) and overall survival (OS) (median DFS: 13 months vs. not reached (NR), p = 0.0096; median OS: not reached, NR vs. NR, p = 0.038), and was an unfavorable prognostic factor for DFS (HR:3.285; 95%CI: 1.526-7.071, p = 0.002) and OS (HR: 2.864, 95% CI: 0.932-8.796, p = 0.066). ConclusionsYAP1 was found to be conversely correlated with neuroendocrine markers and a prognostic factor for worse survival in resected LCNEC patients, and mechanisms need to be further investigated.

Defining the optimal threshold and prognostic utility of pre-treatment hemoglobin level as a biomarker for survival outcomes in head and neck cancer patients receiving chemoradiation

ObjectivesWe sought to define the optimal threshold for anemia in North American head and neck cancer patients and evaluate its role as a prognostic biomarker. Materials and MethodsA single-institution database was queried for patients with head and neck cancer who underwent chemoradiation from January 2005 to April 2021. An optimal threshold of hemoglobin (Hgb) level was defined based on maximum log-rank test statistic. Cox multivariable analysis (MVA), Kaplan-Meier, and propensity score matching were performed to evaluate treatment outcomes. ResultsA total of 496 patients were identified. Threshold for Hgb was determined to be 11.4 for both overall survival (OS) and progression-free survival (PFS). Low Hgb was associated with worse OS (adjusted hazards ratio [aHR] 2.41, 95 % confidence interval [CI] 1.53–3.80, p < 0.001) and PFS (aHR 2.01, 95 % CI 1.30–3.11, p = 0.002). Similar findings were observed among 39 matched pairs for OS (5-year OS 22.3 % vs 49.0 %; HR 2.22, 95 % CI 1.23–4.03, p = 0.008) and PFS (5-year PFS 24.3 % vs 39.1 %; HR 1.78, 95 % CI 1.02–3.12, p = 0.04). Among those with HPV-negative tumors, low Hgb was associated with worse OS (aHR 13.90, 95 % CI 4.66–41.44, p < 0.001) and PFS (aHR 5.24, 95 % CI 2.09–13.18, p < 0.001). However, among those with HPV-positive tumors, low Hgb was not associated with both OS (aHR 1.75, 95 % CI 0.60–5.09, p = 0.31) and PFS (aHR 1.13, 95 % CI 0.41–3.14, p = 0.82). Conclusion and relevanceLow Hgb below 11.4 was an independent adverse prognostic factor for worse survival. It was also prognostic among patients with HPV-negative tumors, but not for HPV-positive tumors.

Survival Estimation, Prognostic Factors Evaluation, and Prognostic Prediction Nomogram Construction of Breast Cancer Patients with Bone Metastasis in the Department of Bone and Soft Tissue Tumor: A Single Center Experience of 8 Years in Tianjin, China.

Purpose Bone metastasis in breast cancer remains globally concerned. Accurate survival estimation would be beneficial for clinical decision-making, especially for the patients with potential indications of surgery. Based on a retrospective cohort from China, the study aimed to construct a prognostic prediction nomogram for breast cancer patients with bone metastasis. Methods Breast cancer patients with bone metastasis diagnosed between 2009 and 2017 in our department were retrospectively selected. The total cohort was divided into construction and validation cohorts (ratio 7 : 3). A nomogram was constructed to predict the probability of survival, and the performance of model was validated. Results A total of 343 patients were enrolled with 243 and 100 patients in construction and validation cohorts, respectively. The median overall survival for the total cohort was 63.2 (95% CI: 52.4–74.0) months. Elevated ALP (HR = 1.71, 95% CI: 1.16–2.51; P=0.006), no surgery for breast cancer (HR = 2.19, 95% CI: 1.30–3.70; P=0.003), synchronous bone metastasis (HR = 1.98, 95% CI: 1.22–3.22; P=0.006), and liver metastasis (HR = 1.68, 95% CI: 1.20–2.37; P=0.003) were independent prognostic factors for worse survival. The independent predictors and other five factors (including age at diagnosis, ER status, PR status, Her-2 status, and the performance of bisphosphonate) were incorporated to construct the nomogram. The C-index was 0.714 (95% CI: 0.636–0.792) and 0.705 (95% CI: 0.705) in the construction cohort and validation cohort, respectively. All the calibration curves were close to the 45-degree line, which indicated satisfactory calibration. Conclusion A retrospective study aiming at prognostic estimation of breast cancer patients with bone metastasis was designed. Four independent prognostic factors were identified and a prognostic nomogram was constructed with satisfactory discrimination and calibration. The model could be used in survival estimation and individualized treatment planning.

Activation of YAP1 by N6-Methyladenosine-Modified circCPSF6 Drives Malignancy in Hepatocellular Carcinoma.

This study advances the understanding of the interplay between m6A methylation and circRNAs in hepatocellular carcinoma, highlighting the potential of circCPSF6 as a therapeutic target.

High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy

PurposeTumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer.Materials and methodsTMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel.ResultsThe study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy.ConclusionThese data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy.Secondary abstractThis retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy.

Adrenocortical Carcinoma: The Value of Lymphadenectomy

Adrenocortical carcinoma (ACC) staging does not account for the number of positive nodes. The prognostic value of quantitative metastatic nodal burden is unknown. The National Cancer Database was retrospectively queried from 2004-2016 to identify patients with Stage I-III ACC undergoing adrenalectomy. Patients who underwent lymphadenectomy (LAD) were further studied. Demographics, TNM staging, tumor characteristics, and surgical approach were analyzed. 386 LADs were identified. The median number of nodes examined was 2 (IQR 2-6), with no difference by surgical approach '[laparoscopic, 3 (1-3); robotic, 1.5 (1-4.5); open, 2 (1-7), p = 0.493]. In LADs with cN0 disease, positive nodes were seen in 17.5% of patients; an average of 6 (1-12) nodes were examined in patients who upstaged to pN1 disease compared with an average of 2 (1-6) nodes in those who remained pN0. Median survival was incrementally worse for patients with more positive nodes (62.8 vs. 21.9 vs. 13.7 vs. 11.3 vs. 10.7 months for 0, 1, 2, 3, and ≥4 positive nodes, respectively, p < 0.01). On multivariate analysis, significant prognostic factors for poor survival included older age, ≥2 comorbidities, pT3, and pT4. The strongest prognostic factor for poor survival was the number of positive nodes (1 node, hazards ratio [HR] 2.3, 95% confidence interval [CI] 1.5-3.6; 2 nodes, HR 1.3, 95% CI 0.6-3.0; 3 nodes, HR 3.0, 95% CI 1.1-8.0; ≥4 nodes, HR 4.0, 95% CI 2.5-6.2). Lymphadenectomy was associated with improved survival (HR 0.82, 95% CI 0.67-0.99). Higher quantitative metastatic nodal burden is a robust prognostic factor for worse survival in ACC.

Sarcopenia diagnosis using different criteria as a predictor of early mortality in patients undergoing hemodialysis

ObjectivesChronic kidney disease (CKD) is a public health problem, causing secondary sarcopenia. The aim of this study was to evaluate sarcopenia using the definitions proposed by European Working Group on Sarcopenia in Older People in 2010 (EWGSOP2010) and 2019 (EWGSOP2019) as an independent prognostic factor for worse survival in patients with CKD undergoing hemodialysis. MethodsMuscle mass, muscle strength, and physical performance were assessed in a cohort of patients with CKD on hemodialysis. The sample consisted of 127 patients (40% >60 y of age) and 36 patients (28.3%) died after a median follow-up length of 23.5 mo (interquartile range= 14.9 – 29). The EWGSOP2010 and EWGSOP2019 definitions were used for diagnosing sarcopenia. Sarcopenia association with mortality by both definitions was investigated using Kaplan–Meier curves and Cox proportional hazard models. The area under the curve, sensitivity, specificity, positive, and negative predictive values for both definitions were also compared. ResultsPatients diagnosed with sarcopenia by both criteria had almost three times higher risk for mortality (95% confidence interval,1.45–6.06 and 1.44–6.13, respectively). Patients classified with severe sarcopenia by both definitions had a significantly lower survival, even after the adjusted analysis. The areas under the curve for EWGSOP2010 and EWGSOP2019 did not significantly differ. The sensitivity/specificity analysis was considered similar for both criteria, and around 70% of the patients was correctly classified. ConclusionSarcopenia, notably severe sarcopenia, diagnosed by EWGSOP2010 or EWGSOP2019 criteria, is an independent prognostic factor for worse survival in this population. Early detection with effective interventions may decrease the higher mortality risk among patients with sarcopenia and CKD.

Prognostic Significance of Preoperative Prognostic Nutritional Index for Overall Survival and Postoperative Complications in Esophageal Cancer Patients.

BackgroundPrognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are the most common factors to estimate nutritional and inflammatory status. The aim of this study is to systematically evaluate the prognostic significance of above nutritional and inflammatory indexes for overall survival (OS) and surgical complications in esophageal cancer patients.MethodsEsophageal cancer patients who underwent esophagectomy were retrospectively collected. PNI, NLR, PLR, and SII were introduced to evaluate the baseline nutritional and inflammatory status.ResultsA total of 407 patients were included in the present study. Kaplan–Meier survival analysis revealed that PNI-low group, NLR-high group and PLR-high group, all showed a significantly shorter OS (34.38% vs 49.46%, P < 0.001; 36.13% vs 48.26%, P = 0.026 and 33.33% vs 48.52%, P = 0.001 respectively), while no significant difference was found in SII groups (42.33% vs 46.31%, P = 0.067). Multivariable analyses identified PNI (P = 0.002) was an independent prognostic factor for OS, but NLR (P = 0.672) and PLR (P = 0.186) were not. Postoperative complications occurred significantly more frequently in the low-PNI group (29.69% vs 13.26%, P < 0.001). However, no significant differences were found in the postoperative complication rates between different NLR (16.67% vs 22.69%, P = 0.124), PLR (18.03% vs 19.61%, P = 0.867) and SII (15.34% vs 20.49%, P = 0.326) groups. Multivariate logistic regression analysis showed only PNI (P = 0.008) was an independent prognostic factor for postoperative complications.ConclusionPreoperative low PNI was not only an independent prognostic factor for worse survival in esophageal cancer patients but also associated with high incidence of postoperative complications.

1582P Thromboembolic disease in COVID-19 cancer patients: Impact on overall survival and prognostic factors

Background: An increased risk of thromboembolic events (TE) is associated with COVID-19 infection. However, information available about thrombosis risk in COVID-19 cancer patients (Ca-P) is still scarce. Methods: We retrospectively evaluated 219 Ca-P who were diagnosed of COVID-19 infection in our institution during the first pandemic wave. The study population was monitored for 12 months, and TE were recorded. A descriptive analysis of baseline and follow-up clinical characteristics was performed. Potential prognostic factors for developing TE and overall survival (OS) were analysed using logistic and cox proportional regression models. Results: Overall TE rate was 13%. TE were reported during COVID-19 hospitalization (52%) and during follow-up (48%), the median time from COVID-19 diagnosis to TE was 12 weeks (w). Reported TE included pulmonary embolism (68%), deep vein thrombosis (16%), and other arterial thrombosis (16%). Pooled mortality rate among patients with TE was 52%, and 41% among patients without TE. Univariate analysis revealed haemoglobin 3000 ng/mL, PCR >5 ng/mL, LDH >190 UI/L and ferritin > 296 ng/mL during follow-up as significant prognostic factors for TE. Only ferritin > 296 ng/mL remained significant after multivariate analysis. Neither being on any specific oncological treatment nor prior anticoagulant therapy influenced TE risk. No differences in OS were found between patients who developed TE and those who did not. Though, diagnosis of TE during COVID-19 hospitalization conferred poorer survival (12 vs 52 w, p=0.02). Also, being hospitalized for COVID-19 infection was a prognostic factor for worse survival (27 vs 52 w, p=0.03). On multivariate analysis, only acute respiratory distress syndrome, metastatic disease, poor performance status, and history of TE before COVID-19 diagnosis remained significant predictors for poorer survival, and thromboprophylaxis during COVID-19 hospitalization as a predictor for better survival outcomes. Conclusions: TE in COVID-19 Ca-P can lead to fatal outcomes. Thrombotic risk may persist after acute infection;therefore, routine active surveillance should be considered. Larger studies are needed for developing a risk prediction tool for TE in COVID-19 Ca-P. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.