On Overall Survival Research Articles

The Impact of the COVID-19 Pandemic and Lockdown on the Outcome of Glioblastoma.

Rapid spread of the SARS-CoV-2 pandemic in 2020 led to an indirect effect on non-COVID patients. Since neuro-oncology cases are unique and brain tumors need a specific therapeutic protocol at proper doses and at the right times, the effects of the pandemic on health care services for patients with glioblastomas (GBs) and their impact on overall survival (OS) and quality of life are not yet known. We conducted a retrospective study of 142 GB patients who underwent surgery, radiation, and chemotherapy before and after the lockdown period, aiming to determine the differences in access to care, treatment modality, and adjuvant therapies, and how the lockdown changed the prognosis. The number of procedures performed for GB during the pandemic was comparable to that of the prepandemic period, and patients received standard care. There was a significant difference in the volume of lesions measured at diagnosis with a decreased number of "accidental" diagnoses and expression of a reduced use by the patient for a checkup or follow-up examinations. Patients expressed a significantly lower performance index in the lockdown period with longer progression-free survival (PFS) in the face of a comparable mean time to OS. Patients treated surgically for GB during the pandemic period had a more pronounced and earlier reduction in performance status than patients treated during the same period the year before. This appears to be primarily due to lower levels of care in the rehabilitation centers and more frequent discontinuation of adjuvant care.

The differences between pure and mixed invasive micropapillary breast cancer: the epithelial–mesenchymal transition molecules and prognosis

PurposeInvasive micropapillary carcinoma (IMPC) of the breast is known for its high metastatic potential, but the definition of pure and mixed IMPC remains unclear.This retrospective cohort study aims to investigate the prognostic significance of the micropapillary component ratio and the expression of critical molecules of epithelial–mesenchymal transition (EMT), including E-cadherin (E-cad), N-cadherin (N-cad), CD44s, and β-catenin (β-cat), in distinguishing between pure and mixed IMPCs.MethodsWe analyzed 100 cases of locally advanced IMPC between 2000 and 2018 and excluded patients who received neoadjuvant chemotherapy. Pure IMPC was defined as having a micropapillary component of over 90%. A comprehensive recording of prognostic parameters was conducted. The IMPC areas were analyzed using the immunohistochemical (IHC) staining method on the microarray set for pure and mixed IMPC patients. Pearson's chi-square, Fisher’s exact tests, Kaplan–Meier analysis, and Cox proportional hazards analysis were employed.ResultsThe comparative survival analysis of the entire group, based on overall survival (OS) and disease-free survival (DFS), revealed no significant difference between the pure and mixed groups (P = 0.480, HR = 1.474 [0.502–4.325] and P = 0.390, HR = 1.587 [0.550–4.640], respectively). However, in the pure IMPC group, certain factors were found to be associated with a higher risk of short survival. These factors included skin involvement (P = 0.050), pT3&4 category (P = 0.006), a ratio of intraductal component (> 5%) (P = 0.032), and high-level expression of N-cad (P = 0.020). Notably, none of the risk factors identified for short OS in pure IMPC cases were observed as significant risks in mixed cases and vice versa. Furthermore, N-cad was identified as a poor prognostic marker for OS in pure IMPCs (P = 0.002).ConclusionThe selection of a 90% ratio for classifying pure IMPCs revealed significant differences in certain molecular and prognostic parameters between pure and mixed groups. Notably, the involvement of N-cadherin in the epithelial–mesenchymal transition (EMT) process provided crucial insights for predicting OS and DFS while also distinguishing between the two groups. These findings strongly support the notion that the pure IMPC subgroup represents a distinct entity characterized by unique molecular characteristics and behavioral patterns.

Impact of sarcopenia and obesity on overall survival in patients with head and neck cancer receiving radiotherapy: A longitudinal study

PurposeTo analyze the impact of sarcopenia and obesity on overall survival (OS) in patients with head and neck cancer (HNC) receiving radiotherapy (RT). MethodsThis prospective longitudinal study recruited 494 patients using convenient sampling. Weight and body composition were assessed before RT (T1), and at the end of RT (T2) using bioelectrical impedance analysis (BIA). The appendicular skeletal mass index was used to define sarcopenia, while the body mass index and fat mass index were used to define obesity. Patient OS was followed and described using Kplan-Meier analysis. Cox proportional hazard regression was used to analyze influencing factors of OS. ResultsThe median follow-up time was 26.2 months (IQR: 18.4–34.4 months). Multivariable models indicated that sarcopenia/obesity type assessed at T1 was not significantly associated with OS. Multivariable models involving body composition at T2 showed that age (P < 0.001), tumor site (P = 0.003), tumor stage (P = 0.024), and sarcopenia/obesity type (P = 0.040) were significantly associated with OS, while sarcopenic patients without obesity at T2 had worse OS. ConclusionsPatients with sarcopenia and no obesity at the end of RT might have worse OS. Healthcare professionals should enhance HNC patients’ management during RT, helping them maintain a certain amount of muscle mass and fat mass to improve their survival.

Survival Prognostication in Patients with Differentiated Thyroid Cancer and Distant Metastases: A SEER Population-Based Study.

Background: For patients with thyroid cancer, distant metastasis is a significant predictor of poor outcome. Since distant metastasis occurs in less than 10% of patients with differentiated thyroid cancer, correlates of survival in this vulnerable patient population remain understudied. This study aimed to identify prognostic groups among patients with differentiated thyroid cancer and distant metastases and to determine the role of, and interactions between, patient and tumor characteristics in determining survival. Methods: We identified adult patients diagnosed with differentiated thyroid cancer with distant metastases from the U.S. SEER-17 cancer registry (2010-2019). Analyses were performed using Cox proportional hazards regression, survival trees, and random survival forest. Relative importance of patient and tumor factors important for disease-specific and overall survival was assessed based on the random survival forest analyses. Results: Cohort consisted of 2411 patients with differentiated thyroid cancer with distant metastases followed for a median of 62 months. Most common histopathologic subtype (86.0%) was papillary thyroid cancer, and the most common sites of distant metastasis were the lungs (33.7%) and bone (18.9%). Cox proportional hazards model illustrated significant associations between survival and the following: patient age (p < 0.001), tumor size (p < 0.01), and site of distant metastasis (p < 0.05). Survival tree analyses identified three distinct prognostic groups based on disease-specific survival (DSS) (5-year survival of the prognostic groups was 92%, 64%, and 41%; p < 0.001) and four distinct prognostic groups based on overall survival (OS) (5-year survival of the prognostic groups was 96%, 84%, 57%, and 31%; p < 0.001). The first split in the survival trees for DSS and OS was by age at diagnosis (≤57 years vs. ≥58 years) with subsequent splits based on presence/absence of lung metastases, tumor size (≤4 cm vs. >4 cm), and patient age. A total of 558 patients (23.1%) died from thyroid cancer, and 757 patients (31.4%) died from all causes during the study period. Conclusions: This study identifies distinct prognostic groups for patients with differentiated thyroid cancer with distant metastases and highlights the importance of patient age, lung metastases, and tumor size for determining both disease-specific and overall survival. These findings inform risk stratification and treatment decision-making in this understudied patient population.

Which Is More Suitable for First-Line Treatment of Extensive-Stage Small Cell Lung Cancer, PD-L1 Inhibitors Versus PD-1 Inhibitors? A Systematic Review and Network Meta-Analysis.

In this network meta-analysis (NMA), the efficiency and safety of PD-1 inhibitors + chemotherapy and PD-L1 inhibitors + chemotherapy were compared in the first-line therapy of patients with extensive-stage small cell lung cancer (ES-SCLC). We searched research databases, conference abstracts, and trial registries and subsequently chose relevant studies and extracted dates. The NMA was conducted to estimate the efficiency and safety of the PD-1 inhibitors + chemotherapy and PD-L1 inhibitors + chemotherapy on overall survival (OS), progression-free survival (PFS), overall remission rate (ORR), and adverse events (AEs). Studies were assessed for quality. Subgroup analyses were used to evaluate study heterogeneity. We included six randomized trials with a total of 3163 patients. Direct comparisons showed that patients who received either PD-1 inhibitors + chemotherapy (HR: 0.71, 95% CI: 0.57-0.87) or PD-L1 inhibitors + chemotherapy (HR: 0.74, 0.61-0.89) demonstrated significantly longer OS than those who received placebo + chemotherapy. The results of the NMA showed that no significant differences in OS (HR 0.96 95% CI: 0.72-1.3), PFS (HR 0.83, 95% CI: 0.51-1.4), and ORR (OR 1.3 95% CI: 0.66-2.5) were observed for PD-1 inhibitors + chemotherapy compared with PD-L1 inhibitors + chemotherapy, but the Bayesian ranking revealed that patients receiving PD-1 inhibitors + chemotherapy tended to have longer OS, PFS benefit, and better treatment response than patients receiving PD-L1 inhibitors + chemotherapy. In terms of safety, no significant difference was observed in their safety profiles. In comparison to placebo + chemotherapy, PD-L1 inhibitors + chemotherapy and PD-1 inhibitors + chemotherapy significantly improved survival for ES-SCLC. According to the available data, PD-L1 inhibitors + chemotherapy and PD-1 inhibitors + chemotherapy had equivalent efficacy and safety; however, the level of evidence of this type of comparison is limited.

Impact of surgical types on overall survival in patients with ductal carcinoma in situ: an analysis based on the SEER database.

Breast cancer, as one of the most common malignancies among women globally, presents a concerning incidence rate, underscoring the importance of addressing the treatment of its precursor lesion, ductal carcinoma in situ (DCIS). Treatment decisions for DCIS, involving the balance between breast-conserving surgery (BCS) and mastectomy, remain an area requiring further investigation. This study aimed to compare influence of different surgical types on overall survival (OS) of patients with DCIS and identify specific subgroups with improved OS to develop an effective survival nomogram for patients. Patient data from the Surveillance, Epidemiology, and End Results (SEER) database for DCIS cohort from 2010 to 2020 were retrieved. Kaplan-Meier (K-M) survival curves were utilized to compare prognostic OS of patients with different surgical methods. Cox regression analysis was employed to determine prognostic factors and establish a nomogram to predict 3-, 5-, and 10-year survival rates. The model was confirmed by Concordance Index (C-index), calibration curves, and receiver operating characteristic (ROC) curves. A total of 71,675 patients with DCIS were included. Patients who underwent subcutaneous mastectomy (SM) demonstrated the best OS compared to other surgical types. Additionally, adjuvant radiotherapy or chemotherapy in combination with surgery significantly improved OS compared to surgery alone. Among DCIS patients aged ≤74 years, those who underwent SM benefited the most in terms of OS, while in the age group of 63-74 years, patients who underwent BCS had significantly higher OS than those who underwent total (simple) mastectomy (TM)/modified radical mastectomy (MRM). Multiple factors were associated with improved OS in DCIS patients, and these factors were integrated into the nomogram to establish OS predictions. The C-index, calibration curves, and ROC curves indicated that the nomogram was suitable for assessing patient prognosis. This study demonstrated that SM treatment yielded the best survival rates for DCIS patients, providing important guidance for future surgical decision-making. Moreover, identifying multiple independent factors related to survival and establishing reliable survival nomograms can assist physicians in developing personalized treatment plans and prolonging patient survival.

The Impact of Local Control on Overall Survival after Y-90 Selective Internal Radiotherapy of Liver Metastases in Oligometastatic Cancer: A Retrospective Analysis.

Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients. A retrospective, single-institution study identified oligometastatic patients with ≤5 non-intracranial metastases receiving unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. The primary endpoint was OS defined from Y-90 SIRT completion to the date of death or last follow-up. Local failure was classified as a progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. With a median follow-up of 15.7 months, 33 patients were identified who had a total of 79 oligometastatic lesions treated with SIRT, with the majority histology of colorectal adenocarcinoma (n = 22). In total, 94% of patients completed the Y-90 lobectomy. Of the 79 individual lesions treated, 22 (27.8%) failed. Thirteen patients received salvage liver-directed therapy following intrahepatic failure; ten received repeat SIRT. Median OS (mOS) was 20.1 months, and 12-month OS was 68.2%. Intralesional failure was associated with worse 1 y OS (52.3% vs. 86.2%, p = 0.004). These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low-metastatic-burden patients.

Effect of concomitant medications on treatment response and survival in non-metastatic castrate resistant prostate cancer: Exploratory analysis of the SPARTAN trial

BackgroundWe performed an exploratory analysis of the SPARTAN trial to determine whether concomitant exposure to several classes of commonly prescribed medications influenced the effect of apalutamide on overall survival (OS) and metastasis-free survival (MFS) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Patients and methodsSPARTAN was a phase III randomized controlled trial in which nmCRPC patients were randomly assigned in a 2:1 ratio to receive androgen deprivation therapy with or without apalutamide. We focused on 5 commonly prescribed classes of medications: metformin, statins, angiotensin converting enzyme inhibitors (ACEI), acetylsalicylic acid (ASA), and proton pump inhibitors (PPI) based on a plausible biological and clinical rationale. To determine the potential effect modification, we applied multivariable Cox regression models for OS and MFS separately with additional interaction terms. To determine the independent association of concomitant medications with OS and MFS, we used IPTW-based log-rank test. A 2-sided p < 0.01 was considered statistically significant. ResultsWe did not find statistically significant differences in effect from apalutamide on OS across subgroups stratified by concomitant exposure to any of the medication classes. While there was some difference in the treatment effect from apalutamide on MFS between patients with concomitant statins (adjusted hazard ratio [aHR]: 0.20; 95 % CI: 0.15–0.28) versus without concomitant statins (aHR: 0.31 [0.24–0.39]), this did not reach the pre-specified threshold of statistical significance (p = 0.011). On IPTW-based analysis, patients treated concomitantly with metformin (median: not reached versus 31 months; p = 0.002), or ACEI (median: 37 versus 29 months, p = 0.006) had significantly improved MFS. ConclusionsIn this post-hoc exploratory analysis of SPARTAN, effects of apalutamide on MFS and OS were consistent across subgroups stratified by exposure to concomitant medications. Exposure to concomitant metformin and ACEI was independently associated with a significant improvement in MFS.

Impact of Tumor Size and Differentiation Grade on Survival After Lobectomy and Segmentectomy for Patients with Early-Stage Lung Adenocarcinoma.

The purpose of this study was to investigate the effect of tumor size and differentiation grade on long term survival in patients with early-stage lung adenocarcinoma (LUAD) after lobectomy and segmentectomy. Patients with stage T1-2N0M0 LUAD who underwent lobectomy and segmentectomy were identified from the Surveillance, Epidemiology, and End Results database. Patients were stratified as grade I (well differentiated), grade II (moderately differentiated), and grade III/IV (poorly differentiated/undifferentiated) carcinomas. The effect of tumor size on overall survival (OS) and lung cancer-specific survival (LCSS) was evaluated using the multivariate Cox regression model, including the interaction between tumor size, type of surgery, and tumor differentiation grade. The inverse probability of treatment weighting method was used to adjust for bias between the groups. A total of 19,857 patients were identified, including 18,759 (94.4%) who underwent lobectomy and 1098 (5.5%) who underwent segmentectomy. A three-way interaction among tumor size, differentiation grade, and type of surgery was observed in the overall cohort. After stratifying by differentiation grade, plots of interaction revealed that lobectomy was associated with improved survival compared with segmentectomy when the tumor size exceeded 23 mm for grade I LUAD and 14 mm for grade II LUAD. No interaction was observed between the studied factors in grade III/IV carcinomas. This study interpreted the interaction between tumor size and type of surgery on long-term survival in patients with early stage LUAD and established a tumor size threshold beyond which lobectomy provided survival benefits compared with segmentectomy.

Non-surgical pancreatic cancer: The role of radiotherapy in prolonging survival, A retrospective cohort study in the SEER database.

Limited research has compared external beam radiotherapy (RT) to non-RT in patients with non-surgical locally advanced pancreatic cancer (LAPC). Therefore, this study investigates the impact of RT on overall survival (OS) in patients with non-surgical LAPC in a real-world context. We conducted an analysis of patients with non-surgical LAPC using data from the Surveillance, Epidemiology, and End Results (SEER) database. This analysis involved the utilization of Kaplan-Meier survival curves and multivariable Cox regression analyses. A total of 5,413 individuals with non-surgical LAPC were included in this analysis. Among them, 2,320 (42.9%) received RT, while 3,093 (57.1%) underwent non-RT treatment. The median OS was 12.0 months for the RT group and 9.0 months for the non-RT group, with a statistically significant difference (P<0.001). Multivariate analysis revealed that RT had a statistically significant impact on OS (HR, 0.86; 95% CI, 0.81-0.91; P<0.001). Propensity score matching (PSM) analysis confirmed a statistically significant association of RT with improved OS (HR, 0.84, 95% CI, 0.79-0.90; P<0.001). These results remained consistent after conducting sensitivity analyses, subgroup analyses, and PSM. The study findings suggest that RT could be advantageous for patients with non-surgical LAPC. Further investigations are warranted to explore the relationship between RT and OS.

Impact of surgical compliance on survival prognosis of patients with ovarian cancer and associated influencing factors: A propensity score matching analysis of the SEER database

PurposeTo evaluate the impact of surgical compliance on overall survival (OS) and cancer-specific survival (CSS) in ovarian cancer patients and identify factors influencing surgical compliance. Materials and methodsData from patients with ovarian cancer in the SEER database (2004–2015) were analyzed to compare the characteristics of patients with high and low surgical compliance. Kaplan-Meier curves and Cox regression models were used to assess the impact of surgical compliance on survival outcomes. Nomograms incorporating surgical compliance and independent prognostic factors were constructed to predict OS and CSS and were validated using internal validation sets. Predictive accuracy was evaluated using Harrell's concordance index (C-index), decision curve analysis (DCA), receiver operating characteristic (ROC) curves, and calibration plots. Binary logistic regression analysis identified factors significantly affecting surgical compliance, and propensity score matching (PSM) was used to adjust for confounders. ResultsAmong the 41,859 patients, 783 (1.87 %) demonstrated poor surgical compliance, while 41,076 (98.13 %) exhibited good compliance. Surgical compliance has emerged as an independent prognostic indicator for ovarian cancer. Patients with high compliance had significantly better OS and CSS rates (P < 0.0001). The prognostic models were internally validated and showed strong discriminative and calibration capabilities. Factors affecting compliance included older age, advanced pathological stage, metastasis, elevated CA-125 levels, and lower income. After PSM, Kaplan-Meier analysis revealed significantly improved survival in patients with good compliance (P < 0.0001). ConclusionSurgical compliance is a pivotal and independent predictor of overall and cancer-specific survival in patients undergoing OC. Factors contributing to lower surgical compliance include advanced age, later tumor stage, metastatic spread, elevated CA-125 levels, and reduced family income.

Developing a prognostic model for skin melanoma based on the persistent tumor mutation burden and determining IL17REL as a therapeutic target

BackgroundOne popular and well-established marker for the immune checkpoint blockade (ICB) response is tumor mutation burden (TMB). Persistent TMB (pTMB), a subset of TMB, provides a better indicator to predict patient ICB therapy outcomes, as shown by some studies. Immune checkpoint drugs have significantly changed how melanoma is treated in recent years.MethodsIn this study, we integrated the TCGA-SKCM database and data of pTMB of TCGA from the paper that first mentioned pTMB and analyzed mutational and Immune characteristics associated with pTMB level in SKCM. Next, the predictive DEGs were identified the subgroups of pTMB by Cox regression and LASSO analyses to construct a pTMB-related signature. Finally, the expression and Biological functions of signature genes was detected, and further validated in vitro assay.ResultsIn the current research, we explored the mutational and immunological features related to the level of TMB in cutaneous melanoma (CM). The high-pTMB subgroup exhibited an increasing incidence of gene changes and higher levels of immune cell infiltration. Subsequently, we established a pTMB-related signature based on the predictive DEGs and found the biological features and immune-associated variables between two distinct risk groups. Lastly, the results of the clinical sample validation demonstrated that the expression of IL17REL was down-regulated in the collected samples of individuals with CM. The in vitro assay results indicated that IL17REL effectively suppressed the proliferation, clonality, and migration of CM cells.ConclusionIn conclusion, we have developed a prediction model associated with TMB and subsequently validated the potential influence of IL17REL on Overall Survival (OS) in patients diagnosed with melanoma.

SMARCA4 alterations in non-small cell lung cancer: a systematic review and meta-analysis

AimsA mutation in the SMARCA4 gene which encodes BRG1, a common catalytic subunit of switch/sucrose non-fermentable chromatin-remodelling complexes, plays a vital role in carcinogenesis. SMARCA4 mutations are present in approximately...

Identification of oxidative stress signatures of lung adenocarcinoma and prediction of patient prognosis or treatment response with single-cell RNA sequencing and bulk RNA sequencing data

Lung adenocarcinoma (LUAD), the most common subtype of lung cancer globally, has seen improved prognosis with advancements in diagnostic, surgical, radiotherapy, and molecular therapy techniques, while its 5-year survival rate remains low. Molecular biomarkers provide prognostic value. Oxidative stress factors, such as reactive nitrogen species and ROS, are crucial in various stages of tumor progression, influencing cell transformation, proliferation, angiogenesis, and metastasis. ROS demonstrate dual roles, affecting tumor cells, hypoxia sensitivity, and the microenvironment. Comprehensive analysis of oxidative stress in LUAD has not been conducted to date. Therefore, we systematically investigated the regulatory patterns of oxidative stress in LUAD based on oxidative stress-related genes and correlated these patterns with cellular infiltration characteristics of the tumor immune microenvironment. The model utilizes single-factor Cox analysis to screen key differential genes with prognostic value and employs least absolute shrinkage and selection operator (LASSO) penalized Cox regression analysis to construct a prognostic-related prediction model. Ten candidate genes were selected based on this model. The risk score was constructed using the coefficients and expression levels of these ten genes. Furthermore, the impact of this risk score on overall survival (OS) was determined. Two genes with the most significant differential expression, SFTPB and S100P, were selected through qRT-PCR. Cell experiments including CCK-8, Edu, transwell assays confirmed their effects on lung cancer cells growth, consistent with the results of bioinformatics analysis. These findings suggested that this model held potential clinical value for evaluating the prognosis of lung adenocarcinoma.

DIPG-52. CEREBROSPINAL FLUID DIVERSION DOES NOT PROLONG OVERALL SURVIVAL IN CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG): A REPORT FROM THE INTERNATIONAL DIPG REGISTRY

Abstract BACKGROUND The role of permanent cerebrospinal fluid (CSF) diversion in the management of patients with diffuse intrinsic pontine glioma (DIPG) is poorly elucidated. There are no standard practice guidelines regarding the role of these neurosurgical interventions in patients with DIPG or large studies regarding the impact of CSF diversion on overall survival (OS) or palliation in this disease. METHODS Data were extracted from subjects registered in the International DIPG registry (IDIPGR). Univariable analyses were performed using the Fisher’s exact test or Wilcoxon rank sum test. Survival was estimated using the Kaplan-Meier method. RESULTS Of n=1104 evaluable patients with DIPG registered in the IDIPGR, n=303 (27.4%) had permanent CSF diversion. Median time from diagnosis to CSF diversion was 1 month (range 0-4 months). There were no significant differences in age, gender or race in subjects with CSF diversion versus no CSF diversion. Patients with CSF diversion had a higher incidence of hydrocephalus at diagnosis (64.1% vs 11.3%, p&amp;lt;0.001). There was no significant difference in OS or post-progression survival (PPS) at 1,2 and 3 years between subjects with permanent CSF diversion compared to those without (p=0.5 and p=0.8, respectively). Median OS was 11 months in both. Median PPS was 7 months (no CSF diversion) and 6 months (CSF diversion). Patients reported less headache and vomiting after permanent CSF diversion compared to pre-diversion (p&amp;lt;0.0001), however steroid use was also significantly higher after CSF diversion (p&amp;lt;0.001). CONCLUSIONS In this, the largest reported international cohort of patients with DIPG with permanent CSF diversion, we show that permanent CSF diversion was not associated with an improvement in OS or PPS. CSF diversion improved headache and vomiting but was also associated with increased rates of steroid use. This highlights the need for consensus guidelines regarding the use of these diversion strategies in patients with DIPG.

Clinicopathological Characteristics and the First Mutational Analysis of Gastrointestinal Stromal Tumors From Mexico: A Single Institution Experience.

Background Gastrointestinal stromal tumors (GISTs) arise from Cajal's interstitial cell precursors and display a variety of genetic mutations, primarily in the KIT and PDGFRA genes. These mutations are linked to tumor location, prognosis, and response to treatment. This study delves into the mutational patterns of GISTs in a Mexican population and their impact on overall survival (OS) and disease-free survival (DFS). Methodology This retrospective study examined 42 GIST cases diagnosed at the Oncology Hospital of the National Medical Center XXI Century between January 2018 and December 2020. Clinical, histological, and immunohistochemical data were gathered, and mutational analysis of KIT and PDGFRA genes was conducted using second-generation sequencing. Results The study group consisted of 52.4% females and 47.6% males, with an average age of 62.6 years. The most common tumor site was the stomach (59.5%), followed by the small intestine (26.2%). KIT mutations were detected in 71.4% of cases, predominantly involving exon 11. PDGFRA mutations were observed in 7.1% of cases. Recurrence was noted in 9.5% of patients, all with high-risk tumors. No significant link was identified between specific mutations and OS or DFS. Conclusions This investigation sheds light on the genetic landscape of GISTs in the Mexican population. While no significant association was established between particular mutations and survival outcomes, the study emphasizes the importance of molecular profiling in treatment decision-making. Further studies with larger sample sizes and longer follow-up periods are necessary to validate these results and explore their clinical relevance.

EPEN-13. PRE-IRRADIATION CHEMOTHERAPY EXPERIENCE FOR PEDIATRIC EPENDYMOMA POLISH PROTOCOL

Abstract BACKGROUND Pediatric ependymomas are aggressive central nervous system malignancies arising from the ependymal linings of ventricles and spinal canal. Despite better understanding of tumor biology ependymomas remain therapeutic challenge in pediatric neurooncology. The role of chemotherapy remains controversial. Herein, we describe the outcomes of patients treated at the largest center in Poland who underwent surgery, pre-irradiation chemotherapy and irradiation regardless of extent of surgical resection. METHODS This retrospective review includes pediatric patients with ependymoma treated according to national protocol at the Children’s Memorial Health Institute. We reviewed histology, disease extent, treatment, and report on overall survival (OS) and progression free survival rates (PFS). Descriptive statistics were analyzed using SPSS software. RESULTS Forty-nine patients were included (median age: 84 months). Most patients (96%) had cranial ependymomas (43% supratentorial and 57% posterior fossa lesions). Disseminated disease was found in 16% of cases. Complete resection was achieved in 43%. All patients received pre-irradiation chemotherapy; 6.1% had progressive disease and 41% achieved complete response (CR). All patients, except one, underwent irradiation (67% focal, 2% focal/ventricular, 29% craniospinal, and 2% whole brain). Thirty-five percent of patients relapsed. Five-year PFS and OS were 69% and 80% respectively. Comparing posterior fossa to supratentorial lesions, there was no difference in response after surgery and pre-irradiation chemotherapy (CR 37% versus 50% (p=0.51)) or irradiation (CR 42% versus 55% (p=0.37)). However, relapse was more likely in posterior fossa ependymomas (OR 0.30 IQR (0.70, 1.29), p=0.03) with lower 5-year PFS (56% versus 85%, p=0.03) and 10-year PFS (52% versus 85%, p=0.02). The benefit of chemotherapy was marked in patients with Grade 3 (5-year OS 82% versus 69%) CONCLUSIONS We describe a large cohort of pediatric ependymoma patients who received pre-irradiation chemotherapy. This strategy did not negatively impact the incidence of progression before irradiation.

Should new organ involvement be included in Response Evaluation Criteria in PSMA Imaging?

The current study is intended to investigate the effect of new organ involvement on overall survival (OS) and modify the Response Evaluation Criteria in PSMA Imaging (RECIP) by including new organ involvement to RECIP 1.0. This retrospective study includes 114 patients diagnosed with metastatic castration-resistant prostate cancer (mCRPC) between September 2017 and June 2022 who had received docetaxel treatment and had baseline and post-treatment prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) images. The inclusion criteria were patients with pre- and post-treatment [18F]FDG PET/CT images and whose [18F]FDG PET images were negative. Those whose data were unavailable, who had additional malignancy, or who received abiraterone, enzalutamide, or Lutetium (Lu)-177 treatment were excluded. Age, Gleason score (GS), TPSA (total prostate-specific antigen) levels, surgical history, and OS information were recorded for each patient. The 114 patients herein had a median age of 72.5 (51-91) years and a median GS of 8 (7-10). New lesions were observed in 59 patients (51.7%) and new organ PSMA uptake was observed in 14 patients (12.2%). In the multivariate Cox regression analysis, volume-based treatment response (vTR)-total lesion PSMA (TLP), RECIP PSMA-VOL, modified RECIP (mRECIP) PSMA-VOL, and mRECIP TLP were independent prognostic factors for mortality (p < 0.001, p = 0.006, p = 0.003, and p = 0.003, respectively). The median OS of patients with new organ involvement and new lesion with PSMA uptake was 9.3months (95% CI 2.1-16.5months) and 11.8months (95% CI 7.4-16.2months), respectively. The study concluded that new organ involvement had a shorter OS than new lesion involvement. In the mRECIP that we developed, unlike RECIP, we demonstrated that both PSMA-VOL and TLP value were independent prognostic factors for mortality.

Hepatocellular carcinoma: An analysis of the expression status of stress granules and their prognostic value.

Hepatocellular carcinoma (HCC) is a global popular malignant tumor, which is difficult to cure, and the current treatment is limited. To analyze the impacts of stress granule (SG) genes on overall survival (OS), survival time, and prognosis in HCC. The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC), GSE25097, and GSE36376 datasets were utilized to obtain genetic and clinical information. Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach, and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression, respectively. The prognostic model's receiver operating characteristic (ROC) curve was produced and plotted utilizing the time ROC software package. Nomogram models were constructed to predict the outcomes at 1, 3, and 5-year OS prognostications with good prediction accuracy. We identified seven SG genes (DDX1, DKC1, BICC1, HNRNPUL1, CNOT6, DYRK3, CCDC124) having a prognostic significance and developed a risk score model. The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group (P < 0.001). The nomogram model's findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort. Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle, RNA editing, and other biological processes. Based on the impact of SG genes on HCC prognosis, in the future, it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.

Prevalence and survival implications of malnutrition and sarcopenia in metastatic breast cancer: A longitudinal analysis

BackgroundMalnutrition and sarcopenia are challenges for patients with metastatic breast cancer and have been proposed as independent prognostic factors. Very few studies have addressed the temporal evolution of these parameters and, notably, the separate and combined analysis of sarcopenia and malnutrition. This study aimed to i) determine the prevalence of malnutrition and sarcopenia, individually and combined, and their evolution over time, ii) identify risk factors for each condition, and iii) explore their impact on overall survival (OS). MethodsThis retrospective study was conducted on 111 patients treated for at least a third-line metastatic breast cancer at the Institut Curie between January 1st and March 31st, 2018.Solitary malnutrition was defined from weight loss and body mass index values while solitary sarcopenia was defined solely based on low muscle mass. We analyzed solitary malnutrition, solitary sarcopenia, and then malnutrition with or without sarcopenia, at three key stages (T1: diagnosis of metastasis, T2: initiation of third-line treatment, and T3: 3-month re-evaluation). Univariate and multivariate logistic regression analyses were conducted to investigate the risk factors. We performed Cox proportional hazards analyses for each variable. ResultsAt T1, the prevalence of solitary malnutrition, solitary sarcopenia and malnutrition with or without sarcopenia was 18.6%, 36.1% and 48.9% respectively, increasing to 27.7%, 45.5% and 56.6% at T2. At T2, in multivariate logistic regression analyses, patients aged over 60 years were at an elevated risk of experiencing solitary malnutrition as well as malnutrition with or without sarcopenia, but not solitary sarcopenia. In multivariate analyses, solitary malnutrition was significantly associated with poorer OS (HR 2.2 [95% CI 1.1-4.1], p=0.02), while solitary sarcopenia and malnutrition with or without sarcopenia showed no association. ConclusionSolitary malnutrition and sarcopenia were highly prevalent in patients with metastatic breast cancer, affecting around a quarter and half of patients respectively at third-line treatment initiation. Notably, solitary malnutrition emerged as a prognostic factor for overall survival, whereas no significant association was observed for solitary sarcopenia or malnutrition with or without sarcopenia. This highlights the critical need for early identification of patients at risk of malnutrition and the importance of timely intervention.