Overall Survival Outcomes In Patients Research Articles

Nomogram for radiation-induced lymphopenia in patients receiving intensity-modulated radiotherapy based-chemoradiation therapy for newly diagnosed glioblastoma: A multi-institutional study

PurposeSevere lymphopenia (SLP) has emerged as a significant prognostic factor in glioblastoma. Intensity-modulated radiation therapy (IMRT)-based radiation therapy (RT) is suggested to minimize the risk of SLP. This study aimed to evaluate SLP incidence based on multi-institutional database in patients with GBM treated with IMRT and develop a predictive nomogram. Patients and methodsThis retrospective study reviewed data from 348 patients treated with IMRT-based concurrent chemoradiation therapy (CCRT) at two major hospitals from 2016 to 2021. After multivariate regression analysis, a nomogram was developed and internally validated to predict SLP risk. ResultsDuring treatment course, 21.0% of patients developed SLP and SLP was associated with poor overall survival outcomes in patients with GBM. A newly developed nomogram, incorporating gender, pre-CCRT absolute lymphocyte count, and brain mean dose, demonstrated fair predictive accuracy (AUC 0.723). ConclusionsThis study provides the first nomogram for predicting SLP in patients with GBM treated with IMRT-based CCRT, with acceptable predictive accuracy. The findings underscore the need for dose optimization and radiation planning to minimize SLP risk. Further external validation is crucial for adopting this nomogram in clinical practice.

DNMT3A Cooperates with YAP/TAZ to Drive Gallbladder Cancer Metastasis.

Gallbladder cancer (GBC) is an extremely lethal malignancy with aggressive behaviors, including liver or distant metastasis; however, the underlying mechanisms driving the metastasis of GBC remain poorly understood. In this study, it is found that DNA methyltransferase DNMT3A is highly expressed in GBC tumor tissues compared to matched adjacent normal tissues. Clinicopathological analysis shows that DNMT3A is positively correlated with liver metastasis and poor overall survival outcomes in patients with GBC. Functional analysis confirms that DNMT3A promotes the metastasis of GBC cells in a manner dependent on its DNA methyltransferase activity. Mechanistically, DNMT3A interacts with and is recruited by YAP/TAZ to recognize and access the CpG island within the CDH1 promoter and generates hypermethylation of the CDH1 promoter, which leads to transcriptional silencing of CDH1 and accelerated epithelial-to-mesenchymal transition. Using tissue microarrays, the association between the expression of DNMT3A, YAP/TAZ, and CDH1 is confirmed, which affects the metastatic ability of GBC. These results reveal a novel mechanism through which DNMT3A recruitment by YAP/TAZ guides DNA methylation to drive GBC metastasis and provide insights into the treatment of GBC metastasis by targeting the functional connection between DNMT3A and YAP/TAZ.

Analysis of demographics and the impact of adjuvant radiotherapy on a nationwide cohort of patients with high-grade spinal meningiomas.

Although typically benign, 5% of spinal meningiomas (SMs) present with higher-grade features (World Health Organization grades 2 and 3). High-grade SMs are poorly studied and the role of adjuvant radiotherapy in their management remains controversial. We hence aimed to study the demographic characteristics of this rare tumor and investigate the outcomes associated with the use of surgery with adjuvant therapy in contrast to surgery alone. The National Cancer Database was queried for patients with SMs from 2004 to 2017. Basic statistics were used to identify differences between low- and high-grade tumors in terms of baseline characteristics. Surgery with and without adjuvant radiotherapy were compared after (1:1) propensity-score matching. Kaplan-Meier survival analysis was conducted to study overall survival. All analyses were performed on R. A total of 13184 patients diagnosed with SMs were included, of whom only 5% (n = 669) had high-grade SMs. Patients with high-grade SMs presented at a younger median age (57 years [IQR: 44-68] versus 65 years [54-75]; P < .001) and were more commonly males (33% vs 20%; P < .001). After propensity-score matching, survival analysis revealed similar overall survival outcomes in patients with high-grade SM undergoing both surgery and radiotherapy as compared to those only receiving surgery (P = .19). This study reveals major demographic differences between high- and low-grade SMs. There were no benefits associated with the use of adjuvant radiotherapy. However, due to confounding, overall survival outcomes between patients receiving surgery alone and those receiving surgery with adjuvant radiotherapy are not causally interpretable.

Survival Disparities By Frontline Clinical Trial Enrollment Status for Treatment of Pediatric Acute Myeloid Leukemia

Introduction: Studies have suggested superior outcomes for patients enrolled on clinical trials for their cancer treatment. While sociodemographic disparities in trial enrollment are well established in adults, the literature in children is mixed and limited. A deeper understanding of disparities in pediatric clinical trial enrollment and potential survival differences is critical to ensure the generalizability of trial results and equitable outcomes. In a cohort of children with AML, we sought to examine (1) differences in sociodemographic and clinical characteristics by trial enrollment status, (2) the impact of trial enrollment on survival, and (3) the potential drivers of survival differences. Methods: A retrospective cohort including all pediatric (age &amp;lt;19 years) patients with AML treated at 10 institutions in the United States from 2011-2018 was established and is being actively expanded to include diagnoses through 2023. Chart abstraction by trained study personnel collected detailed demographic and clinical information. Resource utilization data from the Pediatric Health Information System was merged to ascertain patient acuity. Higher acuity was defined as requiring ICU-level resources for 2 or more organ systems within 72 hours of diagnosis. Only patients who had a frontline therapeutic trial option available at their treating institution were included. This was operationalized as a center-level restriction to patients initiating therapy while any frontline trial was enrolling at the center. We additionally included only patients with complete data for all covariates in this analysis. Statistical Analysis: Demographic and clinical characteristics by trial enrollment status were compared using t-test or Fisher's exact test as appropriate. Cox proportional hazards regression estimated hazard ratios (HR) with a doubly robust estimator (adjusted models only) of 4-year OS and EFS by trial enrollment status. A stepwise propensity score (PS) approach assessed the impact of potential drivers of the associations between trial enrollment and overall survival (OS) and event-free survival (EFS). PS were computed by logistic regression and generated stabilized inverse probability weights used for adjustment. First, a Base PS model including a predefined set of potential confounders (age, sex, weight category, preferred language, risk classification, mean annual hospital AML volume) was created. Additional variables of interest were then sequentially added to the PS. The change in adjusted HR relative to the unadjusted comparison was used to quantify the proportion of the association explained at each step. Results: 342 pediatric patients diagnosed with AML with representation from three distinct frontline clinical trials (AAML1031, AML08, and AML16) were included. Patients who were Black (11% vs. 24%), Hispanic (24% vs. 28%), publicly insured (44% vs. 55%), higher acuity (3% vs. 8%), and high-risk classification (29% vs. 34%) were underrepresented in the trial enrollment group compared to non-trial enrolled (Table 1). In unadjusted analyses, trial enrollment was significantly associated with superior OS (HR=0.69, 95% CI 0.47-0.99, p=0.04); there was no significant difference in EFS (HR=0.95, 95% CI 0.69-1.31, p=0.75). Adjustment for the Base PS accounted for 23% of the observed association between trial enrollment and OS (Figure 1). Acuity explained an additional 7% of the association. Inclusion of race/ethnicity and insurance did not result in further adjustment. In fully adjusted analysis, the association was substantially attenuated (HR=0.93, 95% CI 0.59-1.46, p=0.76). Conclusions: Significant sociodemographic and clinical differences exist in frontline trial enrollment for pediatric AML, which may contribute to worse overall survival outcomes for patients not enrolled on trials. Acuity at diagnosis may be a potential modifiable driver of survival differences. These findings support the need to evaluate enrollment patterns across pediatric clinical trials, including how enrollment disparities impact generalizability of clinical trial results, as well as a critical need for interventions designed to improve equity in healthcare access.

Correlation of SUV on Early Interim PET with Recurrence-Free Survival and Overall Survival in Primary Operable HER2-Positive Breast Cancer (the TBCRC026 Trial).

Predictive biomarkers of response to human epidermal growth factor receptor 2 (HER2)-directed therapy are essential to inform treatment decisions. The TBCRC026 trial reported that early declines in tumor SUVs corrected for lean body mass (SULmax) on 18F-FDG PET/CT predicted a pathologic complete response (pCR) to HER2 therapy with neoadjuvant trastuzumab and pertuzumab (HP) without chemotherapy in estrogen receptor (ER)-negative, HER2-positive breast cancer. We hypothesized that 18F-FDG PET/CT SULmax parameters would predict recurrence-free survival (RFS) and overall survival (OS). Methods: Patients with stage II/III ER-negative, HER2-positive breast cancer received neoadjuvant HP (n = 88). pCR after HP alone was 22% (18/83), additional nonstudy neoadjuvant therapy was administered in 28% (25/88), and the majority received adjuvant therapy per physician discretion. 18F-FDG PET/CT was performed at baseline and at cycle 1, day 15 (C1D15). RFS and OS were summarized using the Kaplan-Meier method and compared between subgroups using logrank tests. Associations between 18F-FDG PET/CT (≥40% decline in SULmax between baseline and C1D15, or C1D15 SULmax ≤ 3) and pCR were evaluated using Cox regressions, where likelihood ratio CIs were reported because of the small numbers of events. Results: Median follow-up was 53.7 mo (83/88 evaluable), with 6 deaths and 14 RFS events. Estimated RFS and OS at 3 y was 84% (95% CI, 76%-92%) and 92% (95% CI, 87%-98%), respectively. A C1D15 SULmax of 3 or less was associated with improved RFS (hazard ratio [HR], 0.36; 95% CI, 0.11-1.05; P = 0.06) and OS (HR, 0.14; 95% CI, 0.01-0.85; P = 0.03), the latter statistically significant. The association of an SULmax decline of at least 40% (achieved in 59%) with RFS and OS did not reach statistical significance. pCR was associated with improved RFS (HR, 0.25; 95% CI, 0.01-1.24; P = 0.10) but did not reach statistical significance. Conclusion: For the first time, we report a potential association between a C1D15 SULmax of 3 or less on 18F-FDG PET/CT and RFS and OS outcomes in patients with ER-negative, HER2-positive breast cancer receiving neoadjuvant HP alone. If confirmed in future studies, this imaging-based biomarker may facilitate early individualization of therapy.

Renal Medullary Carcinoma: A Surveillance, Epidemiology, and End Results (SEER) Analysis

IntroductionRenal medullary carcinoma (RMC) is an aggressive and rare renal malignancy that predominantly affects Black patients but is also found in individuals of other ethnicities. To date, only a few hundred cases have been reported in the urologic literature. Due to this extreme rarity, the exact pathophysiology and optimal treatment have yet to be well described. This study aims to determine the predictors of mortality and overall survival outcomes in patients with RMC. MethodsWe utilized the Surveillance, Epidemiology, and End Results Program (SEER) database 18 registries to retrieve demographic and clinical information on patients with RMC between 1996 and 2018. A multivariate analysis was performed to determine predictors of mortality in the study population. Kaplan–Meier survival curves were then created to display the differences in overall survival of Black versus non-Black patients diagnosed with renal medullary carcinoma during the study period. ResultsWe identified 100 patients diagnosed with renal medullary carcinoma using the SEER Database in the study period. The mean age was 28.0 ± 12.0 (95% confidence interval [CI] 25.7-30.4). Among the patients, 76% were male and 24% were female. Most RMC patients were Black (83%) with only 17% identifying as White. The mean survival in months was 13.8 ± 3.0 (95% CI 7.9-19.7). The majority (70%) of patients in this study presented with distant, metastatic disease at the time of diagnosis. Black patients with RMC were less likely to receive surgery and five times more likely to die in comparison to their White counterparts OR = 5.4 (95% CI 1.09-26.9, P = 0.04). Not only did Black patients have a lower survival rate at 12 mo compared to White patients, but they also continued to experience a sharp decline in survival to 10.2% at 24 mo (P < 0.05) and 7.6% at 48 mo (P < 0.05) following diagnosis of renal medullary carcinoma. ConclusionsThese data confirm that RMC is a rare disease that disproportionately affects Black patients. The prognosis appears to be substantially worse for Black subjects diagnosed with this cancer than non-Black patients. The worse outcomes seen in Black subjects are of an unclear etiology and are yet to be investigated.

A demographic and socioeconomic analysis of risk factors in meningeal melanomatosis.

e14019 Background: Meningeal melanomatosis (MM) is a rare and aggressive central nervous system neoplasm that normally occurs in the leptomeningeal melanocytes. Meningeal melanomatosis represents only 0.06% to 0.1% of all primary brain tumors, but it is accompanied with a very poor prognosis with data showing a mean survival of 10 weeks after diagnosis. Despite intrathecal chemotherapy treatment, only a modest positive effect on survival was observed. Limited research has been done. In this study, demographic factors in patients diagnosed with MM from the National Cancer Database (NCDB) were analyzed to elucidate potentially valuable insights regarding its epidemiology. Methods: A retrospective cohort study using data collected between 2004–2020 from the NCDB included 137 patients with a histologically confirmed diagnosis of MN. The descriptive analysis included an examination of demographic factors such as sex, age, race, Hispanic status, insurance coverage, type of medical facility, and Charleson-Deyo score. Primary site was also analyzed. Results: A total of 137 patients were identified with a diagnosis of MM between 2004 – 2020. The most common primary sites of MM were the meninges, not otherwise specified (NOS) (43.8%), spinal meninges (29.2%) and cerebral meninges (19.0%). In the dataset, 50.4% of diagnosed patients were male. The average age of diagnosis was 51.4 years (SD = 21.5, range = 0 – 90 years). The majority of the individuals (73.7%) had a Charlson-Deyo comorbidity score of 0. Most of the individuals diagnosed with MM were non-Hispanic (83.9%) and 87.6% of patients with diagnosed MM were White. Among the 115 patients with available data for median household income, 37.4% were in the top income quartile. A greater proportion of patients, 54.7%, had private insurance compared to those without insurance or those insured through Medicare or Medicaid. The majority of patients resided in metropolitan counties with a population exceeding 250,000 (71.8%) For patients with documented treatment facility type (N = 99), 56.6% of patients were treated in an academic/research program. Conclusions: This first NCDB analysis fills a crucial void in the existing knowledge on MM. MM affected males and females equally, contrary to published literature which suggested a slight predominance in males. The most common primary sites of diagnosis were the meninges NOS, spinal meninges and cerebral meninges, which supports findings in the literature. This is a novel description of the socioeconomic factors of MM patients in the literature, showing that these patients tend to have higher incomes and reside in densely populated metropolitan areas, and are more likely to receive treatment in an academic medical facility. Additional research is imperative to elucidate the influence of demographic and socioeconomic factors on the diagnosis, treatment options, and overall survival outcomes for patients with MM.

17P Impact of adjuvant chemoradiotherapy on survival outcome compared to other treatment modalities for cervical cancer stage IIIc

Cervical cancer is very common among females. Surgery, chemotherapy and radiotherapy are different treatment options for cervical cancer. In 2018, the FIGO staging system has implemented lymph node status in the staging criteria but didn’t consider the number of positive lymph nodes. The current guidelines recommends primary chemoradiotherapy to treat the advanced stages but combined treatment regimens for node positive cervical cancer remains controversial, so this study aims to evaluate the survival outcome of different treatment modalities with further stratification by the positive lymph node number. We used Surveillance, Epidemiology, and End Results (SEER) database to extract the data of 3146 patients with node positive cervical cancer diagnosed from 2000 to 2018, they were treated with different approaches: adjuvant chemoradiotherapy, adjuvant radiotherapy, surgery without systemic treatment, adjuvant chemotherapy and primary chemoradiotherapy. We divided patients into four groups according to the number of involved lymph nodes: one node, two to three nodes, four to 10 nodes, more than 10 nodes. We used SPSS for data analysis. The overall 5-year survival outcome was higher for adjuvant chemoradiotherapy compared to adjuvant radiotherapy, surgery, primary chemoradiotherapy and adjuvant chemotherapy (68.7%, 63.4%, 59.1%, 47.5%, 40.7% ; P-value >0.00). Out of adjuvant chemoradiotherapy showed better 5-year overall survival outcome in patients with one lymph node involvement 73.1% and in patients with 2-3 positive lymph nodes 63.9%. These results highlighted adjuvant chemo-radiotherapy as the treatment of choice for node cervical cancer stage IIIc, surgery and adjuvant chemoradiotherapy has have qiuet similar survival outcome. We also recommend the number of positive lymph nodes to be implemented in the upcoming FIGO system as a predictor for survival outcome and a factor for the treatment plan. Further evaluation is necessary to weigh the benefit versus side effects of the best regimen for each patient.

Five years follow up of patient receiving prolonged mechanical ventilation: Data for a single center in Taiwan.

The National Association for Medical Direction of Respiratory Care recommended tracking 1-year survival rates (the most relevant outcome) in patients treated with prolonged mechanical ventilation. However, patients treated with prolonged mechanical ventilation had higher mortality rates within the first 2 years after weaning. More knowledge regarding long-term mortality would help patients, families, and clinicians choose appropriate interventions and make end-of-life decisions. In this investigation, we attempted to determine the rates of long-term mortality for all patients treated with prolonged mechanical ventilation over a period of 10 years. The purpose of this investigation was to enhance the overall survival outcomes for patients receiving prolonged mechanical ventilation by identifying the factors affecting the 5-year mortality rates for these patients. Retrospective observational study. In this retrospective study, we explored the influential factors related to the overall survival outcomes of all patients treated with prolonged mechanical ventilation. We enrolled every individual admitted to the weaning unit between January 1, 2012, and December 31, 2016. The length of survival for each patient was estimated from admission to the weaning unit until death or December 31, 2021, whichever came first. We analyzed the data to investigate the survival time, mortality rates, and survival curves in these patients. Long-term follow-up information was gathered for 296 patients who received prolonged mechanical ventilation. There was better mean survival times in patients treated with prolonged mechanical ventilation with the following characteristics (in order): no comorbidities, tracheostomies, and intracranial hemorrhage. Successful weaning, receipt of tracheostomy, an age less than 75 years, and no comorbidities were associated with better long-term overall survival outcomes. Prolonged mechanical ventilation patients had abysmal overall survival outcomes. Even though prolonged mechanical ventilation patients' long-term survival outcomes are tragic, medical professionals should never give up on the dream of enhancing long-term outcomes.

Treatment and Overall Survival Outcomes of Patients with B-Cell Prolymphocytic Leukemia

Background B-cell prolymphocytic leukemia (B-PLL) is a rare hematologic malignancy, accounting for <1% of all chronic B-cell leukemia cases, and is generally associated with aggressive features and poor clinical outcomes. Given its low incidence, there is limited data available regarding practice patterns and treatment outcomes in this population. We aimed to evaluate, on a national scale, the trends and overall survival outcomes of patients with B-PLL. Methods The National Cancer Database was used to identify patients with B-cell PLL from 2004-2019. For patients receiving treatment, the use of single or multiagent therapy and upfront transplant was compared, with the utilization of immunotherapy identified for patients diagnosed 2013 or later, corresponding to the recoding of rituximab and alemtuzumab. Kaplan-Meier and Cox regression analysis was used to compare overall survival (OS) for all B-PLL pts. Survival was compared by year of diagnosis, with diagnosis in 2004-2014 considered to be prior to the availability novel therapies, 2015 and later associated with the introduction of BTK and PI3K inhibitors and 2017 as considered having access to venetoclax. Multivariate analysis was performed adjusting for age, co-morbidity score, facility type, and insurance status. Results Of the 950 B-PLL patients identified, the median age of diagnosis was 72 years (interquartile range 62-80) with 42% of patients being ≥75 years old. The majority (88%) identified as White and were male gender (62%). For those with treatment data available (68%; N=646), the majority of patients (72%) received frontline systemic therapy at diagnosis, whereas 14% were managed with active surveillance, and 14% did not receive any form of treatment. Of the 467 patients receiving upfront treatment, 45% of these patients were treated with single agent therapy, 41% received multiagent chemotherapy, and 14% had an unspecified therapy. For those with transplant and immunotherapy data available, 186 patients received immunotherapy and 39 patients were treated with transplant in the front-line. B-PLL patients were more likely to receive treatment if managed at an academic center (OR 2.34; 95% CI 1.45-3.80, p<0.001), and less likely to receive treatment with each increased year of age (OR 0.95; 95% CI 0.94-0.97, p<0.001) or with increased comorbidity burden (OR 0.52 for Charlson-Deyo comorbidity score ≥2, 95% CI 0.28-0.98, p<0.001). With a median follow-up of 1.5 years, B-PLL patients had a median OS of 2.8 years (95% CI 2.3-3.3), with a 1-, 5-, and 10- year survival of 67%, 39%, and 26%, respectively. Patients managed with upfront active surveillance had a median OS of 7.8 years (95% CI 6.7-9.0 years, p<0.001), and patients who underwent upfront treatment had a median OS of 2.1 years (95% CI 1.5-2.7, p<0.033), with a 1-,5-, and 10- year OS of 65%, 36%, and 29%, respectively (all p<0.03). Patients who did not receive disease directed therapy due to death, hospice care, or contraindication, had a median OS of 1.3 years (95% CI 0.3-2.3). For patients treated with immunotherapy and diagnosed 2013 or later (N=166), median OS was 2.9 years (95% CI 1.8-3.9). On multivariate analysis, factors associated with increased risk of death included increased age (Hazard Ratio [HR] 1.04, 95% CI 1.03-1.05) and higher comorbidity score (HR 1.40, 95% CI 1.27-1.54) (all p<0.001). When examining survival trends by year of diagnosis, patients diagnosed prior to BTK and PI3K inhibitor availability (N=646) had no statistically significant difference in OS compared to those diagnosed 2015 or after (N=149) with a median OS of 2.7 years vs. 3.4 years (p=0.432). Additionally, patients diagnosed 2017-2019, with availability of venetoclax (N=175), also had no significant improvement in median OS (2.6 years; 95% CI 1.7-3.5, p=0.885) referenced to diagnosis from 2004-2014. Conclusions These data comprise the largest study to date evaluating patient outcomes with B-PLL. We found that this disease primarily affects elderly patients with a higher incidence in males compared to females. Though the incorporation of novel therapies in recent years has increased therapy options in B-PLL, these data show no significant improvement in overall survival. The continued poor outcomes of this aggressive disease suggests that there is still a high need for clinical research and novel therapeutic options for these patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Population-Based Analysis of Treatment, Survival, and Demographics in Otologic Malignancies

Introduction: Otologic (external ear, middle ear, and temporal bone) malignancies are relatively uncommon tumors. Their location adjacent to vital structures such as the carotid artery, jugular vein, otic capsule, and temporal lobe makes treatment potentially challenging. Objective: The purpose of this study was to examine overall survival outcomes in patients with otologic malignancies obtained via a population-based cancer database. Methods: A search of the Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients treated for external ear, middle ear, and temporal bone malignancies from 1973-2018. Demographic and overall survival data were compiled and analyzed using Kaplan-Meier and logistic regression analysis. Results: The SEER database identified 9317 patients with otologic malignancies. Multivariate analysis of the SEER data showed that age, race, sex, subsite, histopathological type, overall stage, T, N, and M stage, and treatment type significantly affected overall survival. Conclusion: This study examined data on demographics, treatment, and survival of patients with otologic malignancies utilizing the population-based SEER database. Overall stage and T, N, and M stages, patient age, sex, race, treatment type, and histopathological type all appear to significantly impact overall survival. Patients treated with surgery as part of their treatment regimen appeared to have higher 5-year overall survival than patients treated nonsurgically.

Inflammatory landscape in Xeroderma pigmentosum patients with cutaneous melanoma

Xeroderma pigmentosum (XP) is a DNA repair disease that predisposes to early skin cancers as cutaneous melanoma. Melanoma microenvironment contains inflammatory mediators, which would be interesting biomarkers for the prognosis or for the identification of novel therapeutic targets. We used a PCR array to evaluate the transcriptional pattern of 84 inflammatory genes in melanoma tumors obtained from XP patients (XP-Mel) and in sporadic melanoma (SP-Mel) compared to healthy skin. Commonly expressed inflammatory genes were further explored via GTEx and GEPIA databases. The differentially expressed inflammatory genes in XP were compared to their expression in skin exposed to UVs, and evaluated on the basis of the overall survival outcomes of patients with melanoma. Monocyte subsets of patients with SP-Mel, XP and healthy donors were also assessed. PCR array data revealed that 34 inflammatory genes were under-expressed in XP-Mel compared to SP-Mel. Differentially expressed genes that were common in XP-Mel and SP-Mel were correlated with the transcriptomic datasets from GEPIA and GTEx and highlighted the implication of KLK1 and IL8 in the tumorigenesis. We showed also that in XP-Mel tumors, there was an overexpression of KLK6 and KLK10 genes, which seems to be associated with a bad survival rate. As for the innate immunity, we observed a decrease of intermediate monocytes in patients with SP-Mel and in XP. We highlight an alteration in the immune response in XP patients. We identified candidate biomarkers involved in the tumorigenesis, and in the survival of patients with melanoma. Intermediate monocyte’s in patients at risk could be a prognostic biomarker for melanoma outcome.

Prognostic Implications of Skin Invasion in Locally Advanced Oral Cavity Squamous Cell Carcinoma.

To evaluate the effect of histopathologic skin invasion on 2- and 5-year disease-free survival (DFS) and overall survival (OS) in patients treated with primary surgery for locally advanced oral cavity squamous cell carcinoma (OCSCC). A retrospective case-control study was performed comparing previously untreated patients with pT4a OCSCC with and without skin invasion. Academic medical center. Propensity score-matched cohorts were derived by age, sex, surgical margins, pathologic N classification, adjuvant treatment, and primary tumor site. The Kaplan-Meier method was used to evaluate 2- and 5-year OS and DFS, which were compared between cohorts via the log rank (Mantel-Cox) test statistic. Overall 25 patients were identified to have pathologic skin invasion, and 50 were selected for the matched control group. OS was significantly lower for patients with skin invasion as compared with controls at 2 years (30.8% vs 53.3%, P = .018) and 5 years (16.6% vs 42.2%, P = .01). DFS was significantly lower for patients with skin invasion vs controls at 2 years (23.7% vs 47.7, P = .037) and 5 years (15.8% vs 41.4%, P = .024). Histopathologic skin invasion in OCSCC is associated with dismal prognosis in patients who underwent primary surgical treatment. OS outcomes for patients with skin invasion are comparable to survival of patients with recurrent/metastatic disease and T4N2 disease.

Prospective role and immunotherapeutic targets of sideroflexin protein family in lung adenocarcinoma: evidence from bioinformatics validation.

As lung cancer remains the leading cause of cancer deaths globally, characterizing the tumor molecular profiles is crucial to tailoring treatments for individuals at advanced stages. Cancer cells exhibit strong dependence on iron for their proliferation, and several iron-regulatory proteins have been proposed as either oncogenes or tumor suppressive genes. This study aims to evaluate the prospective therapeutic and prognostic values of the sideroflexin (SFXN) gene family, whose functions involve mitochondrial iron metabolism, in lung adenocarcinoma (LUAD). Differential expression analysis using TIMER and UALCAN tools was first employed to compare SFXNs expression levels between normal and LUAD tissues. Next, SFXNs' prognostic values, biological significance, and potential as immunotherapy candidates were examined from GEPIA, cBioPortal, MetaCore, Cytoscape, and TIMER databases. It was found that all members of SFXN family, except SFXN3, were differentially expressed in LUAD compared to normal samples and within different stages of LUAD. Survival analysis then revealed SFXN1 to be related to worse overall survival outcome in patients with LUAD. Furthermore, several correlations between expression of SFXN1 and immune infiltration cells were discovered. To conclude, our study provides evidence of SFXN family gene's relevance to the prognosis and immunotherapeutic targets of LUAD.

The 21-Gene Recurrence Score in Clinically High-Risk Lobular and Ductal Breast Cancer: A National Cancer Database Study

ObjectiveThe aim of this study was to evaluate whether patients with invasive lobular carcinoma (ILC) are more likely to have discordant clinical and genomic risk than those with invasive ductal carcinoma (IDC) when using the 21-gene recurrence score (RS), and to assess overall survival outcomes of patients with 1–3 positive nodes and RS ≤25 with and without chemotherapy, stratified by histology.MethodsWe performed a cohort study using the National Cancer Database and included patients with hormone receptor-positive, HER2-negative, stage I–III invasive breast cancer who underwent 21-gene RS testing. Our primary outcome was rate of discordant clinical and genomic risk status by histologic subtype. Propensity score matching was used to compare 60-month overall survival in individuals with 1–3 positive nodes and RS ≤25 who did and did not receive chemotherapy.ResultsOverall, 186,867 patients were included in our analysis, including 37,685 (20.2%) patients with ILC. There was a significantly higher rate of discordant clinical and genomic risk in patients with ILC compared with IDC. Among patients with 1–3 positive nodes and RS ≤25, there was no significant difference in survival between those who did and did not receive chemotherapy in the IDC or ILC cohorts. Unadjusted exploratory analyses of patients under age 50 years with 1–3 positive nodes and RS ≤25 showed improved overall survival in IDC patients who received chemotherapy, but not among those with ILC.ConclusionOur findings highlight the importance of lobular-specific tools for stratifying clinical and genomic risk, as well as the need for histologic subtype-specific analyses in randomized trials.

Transarterial chemoembolization combined with lenvatinib versus transarterial chemoembolization combined with sorafenib for unresectable hepatocellular carcinoma: Acomparative retrospective study.

Tyrosine kinase inhibitors target transarterial chemoembolization (TACE)-mediated vascular endothelial growth factor to inhibit tumor revascularization and to slow tumor progression. The present study aimed to compare the clinical outcomes of TACE combined with lenvatinib (TACE-lenvatinib) and TACE combined with sorafenib (TACE-sorafenib) in patients with unresectable hepatocellular carcinoma (HCC). The clinical data of patients diagnosed with unresectable HCC who received TACE-lenvatinib or TACE-sorafenib between January 2018 and April 2021 were retrospectively reviewed. The tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups. A total of 112 patients were enrolled and classified into the TACE-lenvatinib group (n=53) and the TACE-sorafenib group (n=59). The objective response rates of patients in the TACE-lenvatinib and TACE-sorafenib groups were 54.7% and 44.1%, respectively (p=0.260), and the disease control rates (DCRs) were 81.1% and 61.0% (p=0.020). The median PFS time was significantly longer in the TACE-lenvatinib group than in the TACE-sorafenib group (10.7 vs. 6.0months; p=0.002). The median OS time between the TACE-lenvatinib and TACE-sorafenib groups also showed a significant difference (30.5 vs. 20.5months, p=0.018). All treatment-related AEs and grade 3/4 AEs were comparable between the two groups (p>0.05). Compared to TACE-sorafenib, TACE-lenvatinib was associated with better DCR, PFS and OS outcomes in patients with unresectable HCC. In subgroups of Barcelona Clinic Liver Cancer B stage or TACE-refractory patients, TACE-lenvatinib also showed a trend of superiority.

MSR68 Mixture-Cure Modelling of the Overall Survival Outcomes of Patients with Advanced Non-Small Cell Lung Cancer (ANSCLC) Receiving Nivolumab + Ipilimumab in CheckMate-227

This study explores the potential for mixture-cure models (MCM) to capture heterogeneity in life expectancy with nivolumab plus ipilimumab (N+I), given the novel mechanism of action and durable, deep survival response, using the CheckMate-227 (CM227) Part 1 trial of advanced non-small cell lung cancer (aNSCLC).

Does Lymph Node Dissection Impact Adjuvant Treatment or Survival Outcomes in High-Risk Endometrial Cancers?

ObjectivesLymphadenectomy does not improve overall survival outcomes in patients with low-risk endometrial cancers. Sentinel node mapping has a high detection rate and accuracy; however, its prognostic implications have not been well explored. We evaluated the overall survival and therapies received by patients undergoing varied lymph node dissection approaches for high-risk endometrial cancers.MethodsRetrospective review of grade 3 endometrioid and high-grade non-endometrioid cancers at one institution over ten years. Patients who received neoadjuvant therapy and/or debulking of only grossly abnormal lymph nodes were excluded. Data was abstracted from electronic medical records. Chi-squared tests and survival analyses were used to compare groups.ResultsOne hundred and fifty-three patients with grade 3 endometrioid, serous, clear cell, carcinosarcoma, or mixed high-grade on final pathology were identified; 16 had no lymph node dissection, 26 had sentinel lymph nodes, and 111 had complete lymph node dissection. Patients with open surgery were more likely to have complete nodes than sentinel nodes when compared to a minimally invasive approach (p<0.001). Sentinel nodal dissection significantly impacted the utilization of, or modality choice, in adjuvant therapy (p=0.051). Recurrence-free survival and cancer-specific overall survival were not significantly different across the three nodal-assessment groups.Conclusions Sentinel lymph node dissection in high-risk endometrial cancers led to no significant differences in recurrence-free survival or cancer-specific overall survival. While limited by sample size and its retrospective nature, results from this single-institution study are hypothesis-generating and prompt consideration of non-inferiority trials. Performing the least invasive surgery possibly can lead to fewer complications while maintaining overall survival outcomes.

Does lymph node dissection impact adjuvant treatment or survival outcomes in high-risk endometrial cancers?

Studies have shown that lymphadenectomy does not improve overall survival outcomes in patients with type I, low risk endometrial cancers. There is good data supporting that sentinel node mapping has a high detection rate and accuracy in high-risk uterine cancers, however its prognostic and adjuvant treatment implications have not been well explored. We aimed to evaluate the overall survival and adjuvant therapies received by patients undergoing complete versus sentinel lymph node dissection for a diagnosis of grade 3 endometrioid or high-grade non-endometrioid endometrial cancer.

Identifying and characterizing lincRNA genomic clusters reveals its cooperative functions in human cancer

BackgroundEmerging evidence has revealed that some long intergenic non-coding RNAs (lincRNAs) are likely to form clusters on the same chromosome, and lincRNA genomic clusters might play critical roles in the pathophysiological mechanism. However, the comprehensive investigation of lincRNA clustering is rarely studied, particularly the characterization of their functional significance across different cancer types.MethodsIn this study, we firstly constructed a computational method basing a sliding window approach for systematically identifying lincRNA genomic clusters. We then dissected these lincRNA genomic clusters to identify common characteristics in cooperative expression, conservation among divergent species, targeted miRNAs, and CNV frequency. Next, we performed comprehensive analyses in differentially-expressed patterns and overall survival outcomes for patients from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) across multiple cancer types. Finally, we explored the underlying mechanisms of lincRNA genomic clusters by functional enrichment analysis, pathway analysis, and drug-target interaction.ResultsWe identified lincRNA genomic clusters according to the algorithm. Clustering lincRNAs tended to be co-expressed, highly conserved, targeted by more miRNAs, and with similar deletion and duplication frequency, suggesting that lincRNA genomic clusters may exert their effects by acting in combination. We further systematically explored conserved and cancer-specific lincRNA genomic clusters, indicating they were involved in some important mechanisms of disease occurrence through diverse approaches. Furthermore, lincRNA genomic clusters can serve as biomarkers with potential clinical significance and involve in specific pathological processes in the development of cancer. Moreover, a lincRNA genomic cluster named Cluster127 in DLK1-DIO3 imprinted locus was discovered, which contained MEG3, MEG8, MEG9, MIR381HG, LINC02285, AL132709.5, and AL132709.1. Further analysis indicated that Cluster127 may have the potential for predicting prognosis in cancer and could play their roles by participating in the regulation of PI3K-AKT signaling pathway.ConclusionsClarification of the lincRNA genomic clusters specific roles in human cancers could be beneficial for understanding the molecular pathogenesis of different cancer types.