Risk Factor For Poor Survival Research Articles

Analysis of multiple factors influencing the survival of patients with advanced gastric cancer.

The aim of this study was to investigate the main factors influencing the survival of patients with advanced gastric cancer. The clinicopathological data of 120 patients with advanced gastric cancer were analyzed retrospectively, and clinical and pathological data were collected. Tumor tissue staging and grading were re-evaluated, and 5-year overall survival was followed up. The classified data were described by percentages, and the continuous data were described by standard deviations or medians. Univariate analysis was performed using the χ2 test or rank-sum test, followed by Kaplan-Meier survival analysis to calculate the median survival time and 5-year cumulative survival. A multivariate Cox regression model was used to evaluate the independent risk factors affecting survival. The test level was α = 0.05. Patients were followed up for 0 to 60 months, the 5-year overall survival rate was 36.2%, and the median survival time was 53.0 ± 1.461 months. K-M and log-rank test results revealed that tumor location, degree of differentiation, depth of invasion, regional lymph node involvement, and postoperative tumor stage were correlated with a decreased 5-year survival rate (P < 0.05). A multivariate Cox risk regression model was used to analyze the degree of histological differentiation (HR = 1.441; 95% CI = 1.049-1.979; P = 0.024), regional lymph node (HR = 1.626; 95% CI = 1.160-2.279; P = 0.005), and pTNM stage (HR = 2.266; 95% CI = 1.335-3.847; P = 0.002), which are independent risk factors for poor survival. Tumor location (P = 0.191), invasion depth (P = 0.579) and tumor size (P = 0.324) were not found to be independent risk factors. The degree of tumor differentiation, regional lymph node metastasis and postoperative pathological stage were found to be independent risk factors for 5-year overall survival in patients with advanced gastric cancer. Standardized and reasonable lymph node dissection and accurate postoperative pathological staging were very important.

Incidence, Risk Factors, and Outcomes of De Novo Malignancy following Kidney Transplantation.

Introduction: Post-transplant malignancy is a significant cause of morbidity and mortality following kidney transplantation often emerging after medium- to long-term follow-up. To understand the risk factors for the development of de novo post-transplant malignancy (DPTM), this study aimed to assess the incidence, risk factors, and outcomes of DPTM at a single nephrology centre over two decades. Methods: This retrospective cohort study included 963 kidney transplant recipients who underwent kidney transplantation between January 2000 and December 2020 and followed up over a median follow-up of 7.1 years (IQR 3.9-11.4). Cox regression models were used to identify the significant risk factors of DPTM development, the association of DPTM with graft survival, and mortality with a functioning graft. Results: In total, 8.1% of transplant recipients developed DPTM, and the DPTM incidence rate was 14.7 per 100 patient-years. There was a higher mean age observed in the DPTM group (53 vs. 47 years, p < 0.001). The most affected organ systems were genitourinary (32.1%), gastrointestinal (24.4%), and lymphoproliferative (20.5%). Multivariate Cox analysis identified older age at transplant (aHR 9.51, 95%CI: 2.60-34.87, p < 0.001) and pre-existing glomerulonephritis (aHR 3.27, 95%CI: 1.10-9.77, p = 0.03) as significant risk factors for DPTM. Older age was significantly associated with poorer graft survival (aHR 8.71, 95%CI: 3.77-20.20, p < 0.001). When age was excluded from the multivariate Cox model, DPTM emerged as a significant risk factor for poor survival (aHR 1.76, 95%CI: 1.17-2.63, p = 0.006). Conclusion: These findings underscore the need for tailored screening, prevention, and management strategies to address DPTM in an aging and immunosuppressed kidney transplant population.

Efficacy of airway stenting and nasogastric tube insertion in airway-esophageal fistula patients with airways compromised by advanced malignancy.

Whether airway-compromised airway-esophageal fistula (AEF) patients should undergo combined airway and esophageal stenting is controversial. This study was designed to evaluate the survival prognosis and poststent interventions in AEF patients with airways compromised by advanced malignancy with or without airway stents. A retrospective analysis of the medical records, survival times, and poststent interventions of 17 patients with or without airway stents was performed. The causes of AEF were esophageal cancer (11/17, 64.7%), lung cancer (6/17, 29.4%), and thyroid cancer (1/17, 5.9%). All patients received a nasogastric tube (n = 12) or underwent gastrostomy (n = 5) to resume enteral nutrition. Thirteen patients underwent airway stent insertion (13/17, 76.5%), whereas four patients did not. Four patients with a high risk of stent migration received external stent fixation to the trachea. Three of the patients with stents suffered severe granulation tissue formation and needed repeated bronchoscopy interventions. In the stented group, none of the patients developed stent migration, and the overall median survival time was 9months, compared with 1.25 months in the nonstented group (P = 0.04). Cox proportional hazards regression revealed that stent insertion, nasogastric tube insertion, and transcatheter bronchial artery chemoembolization were protective factors against death, whereas surgery-related fistula, fistula larger than 2cm, continued chemotherapy, and age were risk factors for poor survival (P < 0.05). In airway-compromised AEF patients, airway stents and nasogastric tubes are probably the preferred treatments. Airway stenting is tolerable, and routine weekly poststent bronchoscopy is needed in the first month and depending on respiratory symptoms thereafter.

Type 2 Diabetes Mellitus and Non-Metastatic Colorectal Cancer: A Retrospective Study on Survival and Toxicity Profiles.

Being one of the most common cancers accounting for approximately 185 million cases globally, colorectal cancer (CRC) is one of the leading derivers of cancer-related mortalities. A high prevalence of Type 2 diabetes mellitus and CRC was noted, together with a causal link between diabetes and CRC development. Thereby, the goal of this study was to properly evaluate type 2 Diabetes mellitus in non-metastatic colorectal cancer patients, and to highlight its impacts on patient's outcome. Patients with non-metastatic colorectal cancer diagnosed between January 2016 and December 2020 were studied retrospectively. Patients were divided into two groups based on whether or not they had type II diabetes. The clinico-pathological, laboratory, treatment and survival data were gathered. A total of 318 patients were included in this study. The toxicity of the drugs used in CRC patients receiving the treatment protocols (169 in non-T2DM group and 39 in T2DM group), both groups reported close percentage of side effects and a similar frequency of drug toxicity occurrence as well as grade of toxicity, with the exception of neuropathy, which was more common in the T2DM group (33.3% vs 11.2%). As for prognosis, non-T2DM and T2DM patients had a mean progression free survival of (71.4 and 60.83 months, respectively) (p = 0.019). Overall survival was 73.1% for T2DM and 85.3% for non T2DM cases. The median overall survival was not reached for both groups in terms of overall survival. T2DM is considered a risk factor for poor survival among CRC patients. Treatment related toxicity is not affected by the presence or absence of diabetes, yet neuropathy needs further studies for diabetic patients receiving oxaliplatin.

Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).

Prostate cancer among Saudis: a registry review.

Policy makers in Saudi Arabia greatly rely on published studies to make major public health decisions. Prostate cancer (PCa) studies in Saudi Arabia are either outdated or limited to local regions. The authors aim to analyze the Saudi Cancer Registry to determine the incidence of PCa across all regions of the Kingdom and the risk factors of poor prognosis in the population. Patients diagnosed with primary PCa from 1 January 2008 to 31 December 2017 were included in the study from the Saudi Cancer Registry. Incidence rates and risk factors for poor survival were calculated. A total of 3607 PCa patients were retrieved. PCa incidence rates ranged from 0.2 to 1.4 per 100000. Most of the patients were aged 60 and older (86.5%; n=3120), married (97%; n=3497) and lived in the central region (38.1%; n=1375). The mean age at diagnosis was 71.1 (10.8) years. Over half of all tumors were poorly differentiated (64.2%; n=2317), and localized (60.4%; n=2180). The all-time metastasis rate reached 31.4% (n=1131). The lowest mean survival was in those with distant metastasis (P=0.039). Age groups, marital status, tumor morphology, place of residency, and grade were not proven to significantly influence survival. The high metastasis rate and evidence of a greater incidence of newly diagnosed metastatic PCa indicate that the idea of select screening for certain high-risk populations is not farfetched. The authors encourage the promotion of awareness regarding PCa risk factors and screening to optimize prognosis and minimize late presentations and high metastasis rates.

Impact of Tumor Size on Survival Outcome in Esophageal Squamous Cell Carcinoma After Esophagectomy Following Neoadjuvant Chemotherapy.

Large tumor size is a prognostic factor in esophageal squamous cell carcinoma (ESCC). However, the effect of tumor size on outcomes following neoadjuvant chemotherapy (NAC) has not been evaluated. This study aimed to assess the influence of tumor size on prognosis of patients undergoing esophagectomy after NAC. This study was made up of 272 patients who underwent esophagectomy after NAC at Kobe University Hospital. We evaluated the pathological tumor size and determined the cutoff level for tumor size using receiver operating characteristics analysis to the survival status. Cox proportional hazards regression analyses were performed to identify prognostic factors. The patients were categorized into two groups: patients with tumor sizes ≥ 36 mm and < 36 mm. Deep pathological tumor invasion and worse histological response to NAC were associated with tumor size ≥ 36 mm. In patients with pT0-1, pT2, and pT4 ESCC, no significant differences in overall survival (OS) rates were observed between the two groups. In patients with pT3, OS of the tumor size ≥ 36 mm group was significantly worse than that of the tumor size < 36 mm group (p < 0.0001). Multivariate analysis in pT3 patients revealed tumor size ≥ 36 mm was an independent risk factor for OS. The 5-year OS rate was 10% in patients with tumor size ≥ 36 mm pT3 ESCC with pathological lymph node metastasis (p < 0.0001). Tumor size ≥ 36 mm is an independent risk factor for poorer survival in pT3 patients. Furthermore, tumor size ≥ 36 mm with pathological lymph node metastasis in pT3 patients was associated with very poor survival.

The prognostic index PRIMA-PI combined with Ki67 as a better predictor of progression of disease within 24 months in follicular lymphoma.

Progression of disease within 24 months (POD24) is a risk factor for poor survival in follicular lymphoma (FL), and there is currently no optimal prognostic model to accurately predict patients with early disease progression. How to combine traditional prognostic models with new indicators to establish a new prediction system, to predict the early progression of FL patients more accurately is a future research direction. This study retrospectively analyzed patients with newly diagnosed FL patients in Shanxi Provincial Cancer Hospital from January 2015 to December 2020. Data from patients undergoing immunohistochemical detection (IHC) were analyzed using χ2 test and multivariate Logistic regression. Also, we built a nomogram model based on the results of LASSO regression analysis of POD24, which was validated in both the training set and validation set, and additional external validation was performed using a dataset (n = 74) from another center, Tianjin Cancer Hospital. The multivariate Logistic regression results suggest that high-risk PRIMA-PI group, Ki-67 high expression represent risk factors for POD24 (P<0.05). Next, PRIMA-PI and Ki67 were combined to build a new model, namely, PRIMA-PIC to reclassify high and low-risk groups. The result showed that the new clinical prediction model constructed by PRIMA-PI with ki67 has a high sensitivity to the prediction of POD24. Compared to PRIMA-PI, PRIMA-PIC also has better discrimination in predicting patient's progression-free survival (PFS) and overall survival (OS). In addition, we built nomogram models based on the results of LASSO regression (histological grading, NK cell percentage, PRIMA-PIC risk group) in the training set, which were validated using internal validation set and external validation set, we found that C-index and calibration curve showed good performance. As such, the new predictive model-based nomogram established by PRIMA-PI and Ki67 could well predict the risk of POD24 in FL patients, which boasts clinical practical value.

Distinct histological and clinical features associated with pure uterine serous carcinoma: A single institution experience

AimTo ascertain the clinicopathological features, survival, and prognostic factors of pure uterine serous carcinoma (pUSC) and compare its clinicopathological characteristics with those of serous-like grade-3 endometrioid endometrial carcinoma (G3-EEC). MethodConsecutive patients with pUSC and p53 abnormal (p53abn) G3-EEC were retrospectively selected between 2014 and 2022. Histological and immunohistochemical features were reviewed, clinical information was collected, and survival analyses were performed. ResultsEighty-five pUSC patients (mean age: 61.6 years) were included. Histologically, pUSC showed a predominantly glandular growth pattern (80.0 %) with high-grade nuclear atypia and obvious nucleoli and 53 cases showed admixtures of architectural patterns. The p53 aberrant expression rate was 98.8 %. 41.5 %, 53.7 %, and 67.5 % of cases were classified as negative for ER, PR, and WT1, respectively. Six (12.3 %) of 49 cases had a HER2 score of 3+ by immunohistochemistry (IHC). The overall survival and progression-free survival rates were 72.9 % and 63.5 %, respectively. Advanced stage, no adjuvant therapy, and lymph node metastasis were independent risk factors for poor survival in pUSC. Twenty-five p53abn G3-EEC patients were assessed. Women with p53abn G3-EEC were on average, younger than those with pUSC (53.4 vs. 61.6 years, P < 0.001). Papillary structures were observed more commonly in pUSC (16 % vs. 36.5 %, P = 0.042). Positive PR expression was significantly associated with p53abn G3-EEC (P = 0.009). Survival did not differ significantly between the subgroups in univariate and multivariate analyses. ConclusionIn this contemporary series, we affirm the suboptimal prognosis associated with pUSC, and that the survival associated with pUSC and p53abn G3-EEC are not significantly different. pUSC and p53abn G3-EEC have distinct morphological and immunohistochemical characteristics.

Prognosis of incidental pulmonary embolism vs. symptomatic pulmonary embolism in cancer patients: a single-center retrospective cohort study in China

BackgroundThe incidence of incidental pulmonary embolism (IPE) has greatly increased, but its clinical characteristics and outcomes are still controversial. This study aimed to compare the clinical characteristics and outcomes between cancer patients with IPE and patients with symptomatic pulmonary embolism (SPE).Patients/MethodsClinical data of 180 consecutive patients with cancer complicated with pulmonary embolism admitted to Beijing Cancer Hospital from July 2011 to December 2019 were retrospectively collected and analysed. General characteristics, diagnosis time of pulmonary embolism (PE), location of PE, concurrent deep venous thrombosis, anticoagulant treatment, impact of PE on anti-tumor treatment, recurrent venous thromboembolism, rate of bleeding after anticoagulation therapy, survival and risk factors of IPE were compared with SPE.ResultsOf 180 patients, 88 (49%) had IPEs and 92 (51%) had SPEs. Patients with IPE and SPE did not differ in age, sex, tumor type, or tumor stage. Median diagnosis times of IPE and SPE after cancer were 108 (45, 432) days and 90 (7, 383) days, respectively. Compared to SPE, IPE tended to be central (44% versus 26%; P < 0.001), isolated (31.8% versus 0.0%; P < 0.001), and unilateral (67.1% versus 12.8%; P < 0.00). The rate of bleeding after anticoagulation therapy did not differ between IPE and SPE. Patients with IPE had a better prognosis than patients with SPE in terms of 30-, and 90-day mortality, as well as overall survival after diagnosis of PE (median: 314.5 vs. 192.0 days, log-rank P = 0.004) and cancer (median: 630.0 vs. 450.5 days, log-rank P = 0.018). SPE (compared to IPE) was an independent risk factor for poor survival after diagnosis of PE in multivariate analysis (hazard ratio [HR] = 1.564, 95% confidence interval [CI]: 1.008–2.425, p = 0.046).ConclusionsIPE accounts for nearly one half of PE cases among Chinese cancer patients. With active anticoagulation treatment, IPE is expected to achieve better survival rates than SPE.

Oncological impact of unexpected horizontal tumor spread in gastric cancer that requires total gastrectomy.

Gastric cancer often exhibits discrepancies between the gross and pathological tumor boundaries, and the degree of discrepancy may be a tumor characteristic. However, whether these discrepancies influence oncological outcomes remains unclear. The data of patients who underwent total gastrectomy for gastric cancer from 2005 to 2018 were collected. A new parameter, ΔPM, which corresponds to the length of the discrepancy between the gross and pathological proximal boundaries, was calculated and the patients were divided into two groups: patients with long ΔPM and those with short ΔPM. Oncological outcomes were compared between the two groups. A length of 8mm was determined as the cutoff value for long or short ΔPM. Tumor size, growth pattern, pathological type, depth, and esophageal invasion were associated with ΔPM > 8mm. Overall survival of the ΔPM > 8mm group was significantly worse than that of the ΔPM ≤ 8mm group (5-year overall survival: 58% vs 78%; p < 0.0001). Multivariate analysis revealed that ΔPM > 8mm was an independent risk factor for poor survival and peritoneal metastasis. The likelihood ratio test revealed a significant interaction between pT status and ΔPM (p = 0.0007). Circumferential involvement and gross esophageal invasion were poorer survival factors in the ΔPM > 8mm group. ΔPM > 8mm is related to several clinicopathological characteristics and is an independent risk factor for poorer survival and peritoneal metastasis but not local recurrence. ΔPM > 8mm combined with circumferential involvement or esophageal invasion is associated with relatively poor survival outcomes.

Prognostic impact of the loss of E-cadherin and de novo expression of N-cadherin at the invasive front of primary and recurrent oral squamous cell carcinoma.

The epithelial-mesenchymal transition (EMT) is a biological mechanism in multiple pathophysiological diseases. Related alterations in cadherin expression play a crucial role in carcinogenesis, progression, angiogenesis, and immune response. EMT cells exhibit a transition from an epithelial to a mesenchymal phenotype (cadherin-switch). This process is characterized by the de novo development of N-cadherin (N-CAD), which replaces E-cadherin (E-CAD) and signifies an increased migratory capacity and malignant transformation. The cadherin switch is a hallmark of EMT and has been studied in various cancer entities. We predicted that the cadherin switch in the primary and recurrent oral squamous cell carcinoma (re-OSCC) tissues is an inherent characteristic of the tumor, affects the biologic behavior, and further reflects the post-recurrence survival outcome of these patients. Survival outcome was analyzed by calculating the post-recurrence survival of the high-risk group and correlating the standardized h-score-based IHC expression of both cadherin types with the clinical follow-up. 94 patients with re-OSCC were observed within the cohort. Tissue samples from both primary and recurring tumors were collected. There was a significant association between loss of E-CAD expression and both oral cancer-specific and overall survival, (HR=2.72, CI:1.50-4.95, p=0.001) and (HR=3.84, CI:1.93-7.63, p=0.001), respectively, for expression loss higher than 60%. There was no statistically significant correlation between N-CAD de novo expression and Overall, oral cancer-specific and disease-free post-recurrence survival. The current study clearly shows that cadherin-switch, identified as E-CAD loss and N-CAD de novo expression in the invasion front of a re-OSCC, appears to be an inherent histological hallmark that does not change from primary manifestation to recurrence within the same tumor, regardless of the form of adjuvant therapy used for the primary tumor. The loss of E-CAD expression in re-OSCC is an independent risk factor for poor survival, and may be used to stratify therapy and de/escalate the multimodal treatment.

Comparison of survival rates as predicted by total tumor volume or tumor burden score in patients with hepatocellular carcinoma concurrent with fatty liver disease and hepatitis B virus

Objectives To analyze prognostic value of total tumor volume (TTV) and tumor burden score (TBS) in surgically treated patients with hepatocellular carcinoma and concurrent fatty liver disease and hepatitis B virus (FLD-HCC) Methods FLD-HCC patients who treated with hepatectomy from 2010 to 2018 were analyzed. Prognostic performance of TTV and TBS were determined by ROC analysis. Patients were stratified into low and high tumor burden by optimal cutoff value of 113.4 cm3for TTV or 6.3 points for TBS. Survival rates were compared between subgroups and independent risk factors were identified by Cox regression. Correlation between TTV and TBS was evaluated. Results This study enrolled 342 FLD-HCC patients. Survival was significantly higher among patients with low Tumor burden than among those with high Tumor burden (p < 0.001).High TTV and TBS were independent risk factors for poor survival of FLD-HCC (HR: 3.27 (2.17-4.93) and 3.48 (2.31-5.26), respectively, all p < 0.001). ROC analyses revealed that TTV and TBS had comparable discriminative ability in stratifying overall and recurrence-free survival of FLD-HCC. Correlation analysis revealed a strong correlation between TTV and TBS. Conclusions Both TTV and TBS have comparable prognostic value and high TTV/TBS predicts poor survival of patients with FLD-HCC.

Temporal Changes in SARS-CoV-2 Infection Pattern in Patients Admitted with Hematological Diseases—A Single Center Experience from North India

Previous studies have shown the vulnerability of hematological patients with the Coronavirus disease of 2019 (COVID-19). We aimed to compare the outcomes and risk factors for poor survival in patients with hematological conditions hospitalized with COVID-19 infection. Single centre, retrospective, cohort study included all patients with a hematological condition admitted to Rajiv Gandhi Cancer Institute &amp; Research Centre, New Delhi, India between 1 April 2020 and 31 May 2021. Of a total of 154 patients, 81 were in the pre-delta group and 73 were in the delta group out of which 21 (25.97%) in the pre-delta group and 24 (33.88%) patients in the delta group died. Haematological characteristics—age &gt; 60 years, progressive hematological cancer, more than two lines of anti-cancer therapy, and active chemo-immunotherapy or targeted therapy were associated with higher mortality in the delta group. COVID-19 characteristics associated with higher mortality during the delta wave were severity of COVID infection, higher oxygen requirements, and COVID plasma therapy There were no deaths in individuals (n = 15) within the delta group who received COVID-19 vaccination. This study adds to the evidence that patients with hematological diseases are a particularly vulnerable group and the delta variant of the virus is associated with higher mortality. We could identify patient characteristics and features related to COVID-19 infection and underlying hematological conditions that were associated with poor outcomes in the delta sub-group. Vaccination was found to be an effective strategy for overcoming mortality and morbidity in these patients.

KRAS, NRAS, BRAF, and PIK3CA mutation rates, clinicopathological association, and their prognostic value in Iranian colorectal cancer patients

Mutations in KRAS, NRAS, BRAF, and PIK3CA genes are critical factors in clinical evaluation of colorectal cancer (CRC) development and progression. In Iran, however, the data regarding genetic profile of CRC patients is limited except for KRAS exon2 and BRAF V600F mutations. This study aimed to investigate the mutational spectrum and prognostic effects of these genes and explore the relationship between these mutations and clinicopathological features of CRC. To achieve these objectives, mutations in KRAS (exons 2, 3, and 4), NRAS (exons 2, 3, and 4), PIK3CA (exons 9 and 20), and BRAF (exon 15) was determined using PCR and pyrosequencing in a total of 151 patients with colorectal cancer. KRAS, BRAF, NRAS, and PIK3CA mutations were identified in 41%, 5.96%, 3.97%, and 13.24% of the cases, respectively. There were some significant correlations between clinicopathological features and KRAS, PIK3CA, BRAF, and NRAS mutations. Mutations in KRAS and PIK3CA were shown to be independent risk factors for poor survival of the patients at stage I-IV (p <0.0001 and p =0.001, respectively). No significant impact on prognosis was observed in patients with BRAF mutations. Our study revealed the prevalence of CRC biomarkers mutations in Iranian patients and emphasized the role of KRAS and PIK3CA on shorter overall survival rates in this population.

Abstract P2-03-20: Clinical profiling and comprehensive analysis of candidate genes related to breast cancer estrogen receptor intratumour heterogeneity

Abstract 1. Background and Aim Breast cancer has the highest incidence among the world’s population. One third of patients diagnosed with early breast cancer progressed into metastatic outcomes due to the inherent heterogeneity and evolutionary features of tumors. The main clinical manifestation is the discordance of receptor expression in metastases. ESR1 the estrogen receptor (ER) encoding gene, has been proved affected ER expression. Nevertheless, the correlation between ER transformation and the somatic mutation profiles in breast cancer metastatic lesions remains unclear. Availability of advanced high-throughput technologies, and the development of bioinformatics tools has greatly accelerated our cognition of the molecular basis of cancer. In this study, we aimed to evaluate the frequency, clinical characteristics and prognostic value of ER receptor conversion between primary and first metastatic lesions in 115 patients whose primary ER status are positive. We also compared the results of NGS of 42 patients and explored latent genes related to ER discordance in expression. 2. Method Qualified metastatic tumor tissue sequencing information was available for 42 patients. Samples were accessed using the FoundationOne CDx assay (Foundation Medicine, Cambridge, MA, USA) panel including 733 tumor related genes. High frequency mutant genes were defined as the genes count more than 4 times in each group. All data were analyzed using SPSS 25.0 software (Chicago, IL, USA). Pearson’s chi-squared (χ2) test, Fisher’s exact test, were used to test the associations between different variables. The Cox proportional hazard models was used to evaluate the relationship between KMT2C mutation and Disease free survival (DFS) in the patients cohorts. The results with p &amp;lt; 0.05 were considered statistically significant. 3. Results and Conclusions All 115 patients (primary ER status is positive) were divided into two groups, 70(60.87%) patients ER status remained positive while 45(39.14%) patients ER status transformed into negative. The histological type (p=0.008) and DFS (p=0.004) were significantly different in two subgroups. There were no significant correlations between the age at the time of diagnosis, BMI classification, menopausal status, surgery, histological grade, tumor size, lymph node status, metastasis, Ki67, adjuvant radiotherapy, neoadjuvant, metastasis site before second biopsy, first treatment after recurrent and first PFS after rebiopsy. Univariable analysis of DFS proved metastasis to be distinct risk factor for poor survival (hazard ratio [HR] &amp;gt; 1, p = 0.001). By contrast, neoadjuvant proved to be protective factor for better survival (hazard ratio [HR] &amp;lt; 1, p &amp;lt; 0.001). The surgery, histological type, histological grade, tumorsize, metastasis, neoadjuvant, first treatment after recurrent, first PFS after rebiopsy were subsequently analyzed with the multivariable Cox analysis. Metastasis (HR&amp;gt;1, p=0.007) and neoadjuvant (HR&amp;lt;1, p&amp;lt;0.001) remained independent prognostic factors of DFS. We compared the differentially mutated genes in the ER differential expression BC patient groups. Mutations in TP53 (n=24) and PIK3CA (n=19) occurred most frequently in both groups and account for 57.14% and 49.23% separately. Notably, mutations in KMT2C (n=6) was detected in ER+ to – subgroup and accounted for 37.5%. According to the results of NGS, the distribution of KMT2C mutations was different among the two cohorts. We identified the mutation in codon 321 was the hot spot of KMT2C in our patient cohort. Next, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to analyze the enriched pathways of KMT2C. KEGG pathway analysis revealed that patients with KMT2C mutations harbored significantly more mutations in genes involved in the Ubiquitin mediated proteolysis and Lysine degradation signaling pathway. Table 1. Patients’ basic clinicopathological characteristics among two groups Table 2. Univariate and Multivariate Analysis Between Clinicopathological Characteristics and DFS of 115 BC patients Table 3. Mutated Genes Rank and patients number Citation Format: Xi Wang, Yongmei Yin, Ziyi Fu. Clinical profiling and comprehensive analysis of candidate genes related to breast cancer estrogen receptor intratumour heterogeneity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-20.

Adjuvant chemotherapy compared with observation in patients with T2aN0 stage IB lung adenocarcinoma.

For patients with T2aN0 stage IB lung adenocarcinoma, benefits of adjuvant chemotherapy remain controversial. Here, we aimed to evaluate such benefits. This retrospective cohort study was conducted on the database of the National Taiwan Cancer Registry. We analyzed patients with T2aN0 stage IB lung adenocarcinoma (re-classified by AJCC 8th edition) diagnosed during the period from January 2011 to December 2017. They were divided into two groups: (1) group 1: tumor <=3 cm with visceral pleural invasion (VPI); (2) group 2: tumor >3 cm, but <=4 cm. Overall survival (OS) and cancer specific survival (CSS) were evaluated. Risk factors for survival were determined. A total of 2,100 patients with T2aN0 stage IB lung adenocarcinoma (1,265 in group 1 and 835 in group 2) were enrolled for study. The proportions of patients receiving adjuvant chemotherapy in group 1 and 2 were 39.1% and 68.6%, respectively. Amongst group 1 patients, adjuvant chemotherapy was not an independent risk factor for OS and CSS. Amongst group 2 patients, high-grade histologic findings and receiving sublobar resection were two risk factors for poorer survival. Adjuvant chemotherapy was also associated with an OS (adjusted hazard ratio (aHR), 0.52; 95% confidence interval (CI), 0.38-0.72; P<0.001) and CSS (aHR, 0.54; 95% CI, 0.37-0.78; p=0.001) benefit regardless of the presence or absence of risk factors. For patients with T2aN0 stage IB lung adenocarcinoma, adjuvant chemotherapy improved OS and CSS in those with tumors >3 cm, but <=4 cm.For patients with tumors <=3 cm with VPI, adjuvant chemotherapy had no survival benefit.

Older liver grafts from donation after circulatory death are associated with impaired survival and higher incidence of biliary non-anastomotic stricture

BackgroundGrafts from older donors after circulatory death were associated with inferior outcome in liver transplants in the past. But it has seemed to remain controversial in the last decade, as a result of modified clinical protocols, selected recipients, and advanced technology of organ perfusion and preservation. The present study aimed to examine the impact of older donor age on complications and survival of liver transplant using grafts from donation after circulatory death (DCD). MethodsA total of 944 patients who received DCD liver transplantation from 2015 to 2020 were included and divided into two groups: using graft from older donor (aged ≥ 65 years, n = 87) and younger donor (age < 65 years, n = 857). Propensity score matching (PSM) was applied to eliminate selection bias. ResultsA progressively increased proportion of liver transplants with grafts from older donors was observed from 1.68% to 15.44% during the study period. The well-balanced older donor (n = 79) and younger donor (n = 79) were 1:1 matched. There were significantly more episodes of biliary non-anastomotic stricture (NAS) in the older donor group than the younger donor group [15/79 (19.0%) vs. 6/79 (7.6%); P = 0.017]. The difference did not reach statistical significance regarding early allograft dysfunction (EAD) and primary non-function (PNF). Older livers had a trend toward inferior 1-, 2-, 3-year graft and overall survival compared with younger livers, but these differences were not statistically significant (63.1%, 57.6%, 57.6% vs. 76.9%, 70.2%, 67.7%, P = 0.112; 64.4%, 58.6%, 58.6% vs. 76.9%, 72.2%, 72.2%, P = 0.064). The only risk factor for poor survival was ABO incompatible transplant (P = 0.008) in the older donor group. In the subgroup of ABO incompatible cases, it demonstrated a significant difference in the rate of NAS between the older donor group and the younger donor group [6/8 (75.0%) vs. 3/14 (21.4%); P = 0.014]. ConclusionsTransplants with grafts from older donors (aged ≥ 65 years) after circulatory death are more frequently associated with inferior outcome compared to those from younger donors. Older grafts from DCD are more likely to develop NAS, especially in ABO incompatible cases.

Exploring optimal therapeutic management of STAGE IA PDAC in the era of neoadjuvant chemotherapy.

712 Background: Neoadjuvant chemotherapy (NAT) is currently recommended for non-metastatic pancreatic ductal adenocarcinoma (PDAC). Data on the optimal NAT duration and the proper post-surgical chemotherapy (PSC) are lacking, especially for patients (pts) who yielded a pathological stage IA. Methods: We retrospectively analyzed the outcome of PDAC pts resected between 2015 and 2020 at our institution after NAT yielding a pathologic stage of PDAC ypT1N0. Pts were analyzed basing on NAT duration (aim 1) and PSC indication (yes/no) and type (aim 2). The primary endpoint was median event-free survival (EFS) for aim 1 and median disease free-survival (DFS) for aim 2. As per secondary endpoints, overall survival (OS) and the prognostic role of clinical and pathological variables was assessed (baseline CA19.9 level; pre-operative Ca19.9 level, basal vascular involvement, grading, perineural invasion, R1 resection). Results: During the study period a total of 756 pts were resected, 363 (48%) after NAT. Of them, 72 pts (20%) achieved a pathological ypT1N0 (ypIA). Among this group 16 pts (22%) showed a T1a-T1b, 62 pts (86%) had a G1/G2 tumor, 60 pts (83%) had a R0, 36 pts (50%) had a perineural invasion and 33 (46%) had a tumor regression grade marked or completed. For aim 1 we compared 34 pts (47%) treated with NAT for not more than 4 months (Group A1) and 38 pts (53%) treated for at least 4 months (Group B1). Baseline, biochemical and radiological variables were similar between the 2 groups. No statistical difference was found in EFS (Group A1: median 46 months/ Group B1: median not reached). For aim 2 we compared 10 pts (14%) who received the same chemotherapy regimen in NAT and PSC (Group A2), 35 pts (49%) who received a different chemotherapy regimen in NAT and PSC (Group B2) and 27 (14%) pts who did not receive any PSC (Group C2). PSC were gemcitabine/nab-paclitaxel (10%) and mFOLFIRINOX (90%) in group A2, whereas gemcitabine/nab-paclitaxel (17%), mFOLFIRINOX (3%), gemcitabine (51.5%), capecitabine (17%), gemcitabine/capecitabine (8.5%), PEXG (3%) in group B2. DFS were 24 months for group B2, whereas median was not reached for group A2 e C2 (p=0.006). No statistical difference was found in OS among the groups. At multivariate analysis only grading (G3) emerged as independent factor for poor prognosis. Conclusions: In ypIA pts NAT duration and or type seem to be unrelated to the outcome. PSC performed with alternative and depotentiated chemotherapy as compared to NAT, seem to be related to a higher rate of disease recurrence. Poor differentiated/G3 tumors is confirmed as independent risk factor for poor survival in this population.

Contemporary outcomes of surgical resection for chest wall chondrosarcoma

ObjectiveChondrosarcoma is the most common primary malignant chest wall tumor and is historically associated with poor prognosis. Recommendations regarding surgical excision are on the basis of small, single-institution studies. We used a large national database to assess outcomes of surgery for chest wall chondrosarcoma (CWC) hypothesizing that surgical excision remains standard of care. MethodsThe National Cancer Databases for bone and soft tissue were merged to identify patients with chondrosarcoma from 2004 to 2018. Clinical and demographic characteristics of CWC were compared with chondrosarcoma from other sites. The primary outcome was overall survival described using Kaplan–Meier estimate. Univariable and multivariable Cox analysis was used to determine risk factors for poor survival among CWC patients who underwent surgery. Multivariable analysis of predictors of margin status was performed because of worse prognosis associated with positive margins. ResultsAmong 11,925 patients with chondrosarcoma, 1934 (16.2%) had a CWC. Relative to other sites, CWC was associated with older age, male sex, White race, surgical resection, and care at a nonacademic institution. CWC was associated with 1-, 3-, 5-, and 10-year survival of 91.5%, 82.0%, 75.5%, and 62.7%, respectively. In univariable analysis, survival was associated with surgery (hazard ratio, 0.02; P < .001) and adversely affected by positive margins (hazard ratio, 2.66; P < .001). Multivariable analysis showed larger tumor size was independently associated with increased risk for positive margins (odds ratio, 1.04; 95% CI, 1.011-1.075). ConclusionsCWC represents a different cohort of patients relative to chondrosarcoma from other sites. Surgical excision remains the optimal treatment, and positive margins are associated with poor prognosis.