Cancer Clinical Outcomes Research Articles

Low albumin-to-creatinine ratios (ACR) are associated with poor outcomes in cancer patients

BackgroundThe albumin-to-creatinine ratio (ACR) is known to predict prognosis in liposarcoma patients, but its role in other tumors remains unclear. This study aimed to evaluate the prognostic relationship between ACR and common solid tumors.MethodsData from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) between 2013 and 2022 were used to analyze patients under 65 years old with solid tumors. Patients were divided into a training cohort (n = 12,027) and a validation cohort (n = 7,985) using simple random sampling. Correlation analysis, Kaplan–Meier method, and restricted cubic spline analysis were conducted to explore ACR's relationship with overall survival (OS). Multivariable logistic regression assessed associations between ACR and Patient—Generated Subjective Global Assessment (PG-SGA), Length of Stay (LOS), and Karnofsky Performance Status (KPS).ResultsIn Cox regression, higher ACR levels were associated with better OS in solid tumor patients. Specifically, when using the cutoff value with low ACR as the reference, higher ACR levels were significantly associated with improved OS. For nasopharyngeal carcinoma (HR = 0.49, 95% CI: 0.35–0.67, P < 0.001), gastrointestinal tract tumors (HR = 0.84, 95% CI: 0.74–0.95, P = 0.007), and urogenital neoplasms (HR = 0.55, 95% CI: 0.43–0.71, P < 0.001), higher ACR levels were linked to better OS. When ACR was categorized into tertiles, the results were consistent with those observed using the cutoff value. In gastrointestinal tract tumor patients, higher ACR levels were linked to lower PG-SGA scores and improved KPS scores (P < 0.05). In urogenital neoplasm patients, higher ACR levels were associated with improved KPS scores (P < 0.05).ConclusionElevated ACR levels were significantly associated with improved OS in cancer patients, particularly in nasopharyngeal carcinoma, gastrointestinal tract tumors, and urogenital neoplasms. ACR was also linked to better nutritional and functional status, suggesting its potential as a prognostic biomarker.

Different PD-L1 Assays Reveal Distinct Immunobiology and Clinical Outcomes in Urothelial Cancer.

Testing for PD-L1 expression by immunohistochemistry (IHC) is used to predict immune checkpoint blockade (ICB) benefit but has performed inconsistently in urothelial cancer (UC) clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on UC samples using the SP142 and 22C3 assays from the phase 3 IMvigor130 trial and found discordant findings summarized by four phenotypes: PD-L1 positive by both assays (PD-L1 double positive; PD-L1DP), PD-L1 positive by the SP142 assay only (SP142 single positive; SP142SP), PD-L1 positive by the 22C3 assay only (22C3 single positive; 22C3SP), and PD-L1 negative by both assays double negative (PD-L1 double negative; PD-L1DN). PD-L1DP and SP142SP UCs were associated with more favorable ICB outcomes and increased dendritic-cell (DC) infiltration. SP142 PD-L1 staining co-localized with DC-LAMP, a DC marker, while 22C3 staining was more diffuse. 22C3SP UCs, associated with worse outcomes, were enriched in tumor cell-dominant PD-L1 expression. Multiplex IHC in an independent ICB-treated cohort confirmed that tumor cell-dominant PD-L1 expression was associated with shorter survival. Using different PD-L1 assays, we uncovered that SP142 may preferentially stain PD-L1-expressing DCs, key to orchestrating antitumor immunity, while tumor cell-dominant PD-L1 expression, which underlies a subset of "PD-L1 positive" specimens, is associated with poor ICB outcomes.

Impact of time to treatment initiation on the development of cachexia and clinical outcomes in lung cancer.

Pre-cancer onset of cachexia raises uncertainties regarding the optimal timing for early intervention in lung cancer patients. We aimed to examine changes in physical function, nutritional status, and cachexia incidence in patients with lung cancer from the initial visit to treatment initiation and determine the effect of these changes on lung cancer treatment. This single-center retrospective cohort study enrolled patients suspected of having advanced lung cancer who visited Kansai Medical University Hospital between January and February 2023 and were definitely diagnosed with the disease. Patients were categorized into three groups based on their cachexia status: those with cachexia at initial diagnosis (group C), those who developed cachexia between the initial visit and treatment initiation (group OC), and those without cachexia (group NC). Out of 61 patients, 21 had cachexia at their first outpatient visit (group C). The time between the first visit and treatment initiation was 42.5days. The rate of cachexia in patients with stage IV lung cancer in group OC was significantly higher than that in patients with other stages (P=0.008). Of the 33 patients with advanced lung cancer, 11 received supportive care only. The first-line treatment induction rate for the OC group was low. Half of the patients declined chemotherapy and received the best supportive care; their disease control rate (37.5%) was significantly worse than that of the other groups (P=0.007). Cachexia negatively impacts the effectiveness of initial cancer treatment, necessitating early anti-cachexia interventions at the first clinical visit.

IL-1β in Neoplastic Disease and the Role of Its Tumor-Derived Form in the Progression and Treatment of Metastatic Prostate Cancer.

Since its discovery, IL-1β has taken center stage as a key mediator of a very broad spectrum of diseases revolving around immuno-mediated and inflammatory events. Predictably, the pleiotropic nature of this cytokine in human pathology has led to the development of targeted therapeutics with multiple treatment indications in the clinic. Following the accumulated findings of IL-1β's central modulatory role in the immune system and the implication of inflammatory pathways in cancer, the use of IL-1β antagonists was first proposed and then also pursued for oncology disorders. However, this approach has consistently relied on the perceived need of interfering with IL-1β synthesized and secreted by immune cells. Herein, we discuss the importance of IL-1β derived from cancer cells which impacts primary tumors, particularly metastatic lesions, separately from and in addition to its more recognized role in immune-mediated inflammatory events. To this end, we focus on the instrumental contribution of IL-1β in the establishment and progression of advanced prostate adenocarcinoma. Special emphasis is placed on the potential role that the standard-of-care treatment strategies for prostate cancer patients have in unleashing IL-1β expression and production at metastatic sites. We conclude by reviewing the therapeutics currently used for blocking IL-1β signaling and propose a rationale for their concomitant use with standard-of-care treatments to improve the clinical outcomes of advanced prostate cancer.

CD4+FOXP3Exon2+ regulatory T cell frequency predicts breast cancer prognosis and survival.

CD4+FOXP3+ regulatory T cells (Tregs) suppress immune responses to tumors, and their accumulation in the tumor microenvironment (TME) correlates with poor clinical outcome in several cancers, including breast cancer (BC). However, the properties of intratumoral Tregs remain largely unknown. Here, we found that a functionally distinct subpopulation of Tregs, expressing the FOXP3 Exon2 splicing variants, is prominent in patients with hormone receptor-positive BC with poor prognosis. Notably, a comprehensive examination of the TCGA validated FOXP3E2 as an independent prognostic marker in all other BC subtypes. We found that FOXP3E2 expression underlies BCs with defective mismatch repair and a stem-like signature and highlights pathways involved in tumor survival. Last, we found that the TME induces FOXP3E2 through the CXCL12/CXCR4 axis and confirmed the higher immunosuppressive capacity of FOXP3E2+ Tregs derived from patients with BC. Our study suggests that FOXP3E2+ Tregs might be used as an independent biomarker to predict BC prognosis and survival and to develop super-targeted immunotherapies.

IBI310 plus sintilimab vs. placebo plus sintilimab in recurrent/metastatic cervical cancer: A double-blind, randomized controlled trial.

It remains unclear whether adding CTLA-4 blockade to PD-1/PD-L1 blockade improves clinical outcomes in cervical cancer (CC). In this randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov: NCT04590599), patients with recurrent/metastatic CC (R/M CC) who experienced disease progression after or during platinum-based chemotherapy were enrolled from 37 centers across China and randomly assigned (1:1), stratified by PD-L1 expression and prior treatment lines, to receive either IBI310 plus sintilimab or placebo plus sintilimab intravenously every 3weeks for 12weeks, followed by sintilimab alone. The primary endpoint was the objective response rate (ORR). Pivotal secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. 205 patients were randomized to receive IBI310-sintilimab (n= 103) or placebo-sintilimab (n= 102). The ORR difference between the IBI310-sintilimab arm (32.3%, 95% confidence interval [CI]: 23.3%-42.5%) and the placebo-sintilimab arm (23.5%, 95% CI: 15.5%-33.1%) was not significant (p= 0.17). IBI310-sintilimab and placebo-sintilimab exhibited median PFS values of 3.6 (95% CI: 2.7-6.3) and 4.2months (95% CI: 2.8-6.2), respectively (hazard ratio [HR]= 0.91, 95% CI: 0.65-1.27; p= 0.58). The median OSs were 13.9months (95% CI: 11.5-25.6) in the IBI310-sintilimab arm and 17.2months (95% CI: 13.7-25.9) in the placebo-sintilimab arm (HR= 1.12, 95% CI: 0.79-1.58; p= 0.54). Adding IBI310 to sintilimab increased the incidence of grade ≥3 treatment-related adverse events (55% versus 19%). Compared to single-agent PD-1/PD-L1 blockade, dual blockade of CTLA-4 and PD-1/PD-L1 did not significantly improve clinical outcomes in R/M CC. This work was funded by Innovent Biologics (Suzhou).

Clinical Characteristics of and Treatment Pattern for EGFR-Amplified Colorectal Cancer.

To compare clinicopathologic features and clinical outcomes of metastatic colorectal cancer (mCRC) based on EGFR amplification status. Patients with mCRC who underwent next-generation sequencing using a targeted 244-gene panel from 2016 to 2021 were identified and screened for EGFR copy numbers. Cases with at least 5 copies were reviewed for tumor purity adjustment, and those with an adjusted copy number of ≥6 were defined as EGFR-amplified (EGFR amp+). Their clinical characteristics were compared with those without EGFR amplification (EGFR amp-). Among 2,421 patients, 35 (1.4%) were EGFR amp+. Clinical characteristics did not significantly differ according to EGFR amplification status, but EGFR amp+ cases had fewer instances of peritoneal seeding (8.6% vs. 21.8%). Overall survival (OS) tended to be better in EGFR amp+ patients compared with EGFR amp- patients (median OS 76 vs. 37 months, p=0.15). Among 572 patients who received anti-EGFR antibody-based chemotherapy (anti-EGFR CTx) during disease course, mOS tended to be better in 16 EGFR amp+ patients (79 months) compared with 556 EGFR amp- patients (39 months, p=0.048). Seven out of 35 EGFR amp+ patients were treated with front-line anti-EGFR CTx, and their progression-free survival did not differ from that of EGFR amp- patients treated with front-line anti-EGFR CTx (20 vs. 14 months, p=0.344). This study may suggest a favorable predictive impact of EGFR amplification in patients treated with anti-EGFR CTx. However, the benefit of front-line anti-EGFR antibody treatment in this group was not notable.

GTF2I acts as a novel tumor suppressor transcription factor and shows Favorable prognosis in renal cancer.

The role of GTF2I (General Transcription Factor2I) alteration has already been reported in thymic cancer as a valuable biomarker. However, the association of GTF2I mutation with renal cancer for prognosis of immunotherapy is not yet examined. The biologic and oncologic significance of GTF2I in renal cancer was examined at multiomics level such as mutation, copy number alteration, structural variants. The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA) were used to retrieve the omics data. The expression of GTF2I mRNA was quite significant in case of renal caner. Correlation among the GTF2I mRNA, mutation, CNA and structural variants was also studied. Interactome of GTF2I was also constructed using STRING database. Gain, amplification, and missense mutation exhibited a positive correlation between GTF2I mRNA expression and non-structural variants. Similarly, GTF2I mRNA expression and copy number alterations from GISTIC were positively correlated. High expression of GTF2I was associated with better overall survival indicating the less aggressive clinical features. Insight Box Investigating GTF2I's complex function as a tumor suppressor transcription factor in renal carcinoma provides fresh insights into its biologic and oncologic importance, especially when considering the prognosis of immunotherapy. Little is known about its possible use as a biomarker for renal cancer. Using a multiomics approach and utilizing information from the Human Protein Atlas (HPA) and The Cancer Genome Atlas (TCGA), our study clarifies the intricate relationship between mRNA expression, GTF2I changes, and clinical outcomes in renal cancer. Our results indicate that GTF2I expression may be used as a prognostic indicator because it is positively correlated with favorable survival outcomes. Furthermore, the molecular interactions behind GTF2I's functional significance in renal cancer are revealed by interactome analysis utilizing the STRING database, providing important information for further study and treatment approaches.

Proximity Labeling: Precise Proteomics Technology for Mapping Receptor Protein Neighborhoods at the Cancer Cell Surface.

Cell surface receptors are pivotal to cancer cell transformation, disease progression, metastasis, early detection, targeted therapy, drug responses, and clinical outcomes. Since they coordinate complex signaling communication networks in the tumor microenvironment, mapping the physical interaction partners of cell surface receptors in vivo is vital for understanding their roles, functional states, and suitability as therapeutic targets. Yet traditional methods like immunoprecipitation and affinity purification-mass spectrometry often fail to detect key but weak or transient receptor-protein interactions. Proximity labeling, a cutting-edge proteomics technology, addresses these technical challenges by enabling precise mapping of protein neighborhoods around a receptor target on the cell surface of cancer cells. This technique has been successfully applied in vitro and in vivo for proteomic mapping across various model systems. This review explores the fundamental principles, technologies, advantages, limitations, and applications of proximity labeling in cancer biology, focusing on mapping receptor microenvironments. By advancing mechanistic insights into cancer cell receptor signaling mechanisms, proximity labeling is poised to transform cancer research, improve targeted therapies, and illuminate avenues to overcome drug resistance.

Sex Differences in Clinical Features and Survival Outcomes of Esophageal Cancer: A Comparative Study in the Korean Population.

Esophageal cancer is a predominantly male disease. However, the sex differences associated with esophageal cancer have not been thoroughly investigated. This study aimed to evaluate the differences between esophageal cancer in males and females in the Korean population. We assessed patients diagnosed with esophageal cancer between 2005 and 2015 at a tertiary referral center. The clinical features of patients, histopathologic characteristics of tumors, and treatment and survival outcomes were compared between male and female patients. We enrolled 2,068 patients, comprising 1,924 (93.0%) males and 144 (7.0%) females. The median age at diagnosis was younger for females than males (65 vs. 63 years, p=0.004). Squamous cell carcinoma was the predominant pathological type (99.0% in males and 93.1% in females); however, the proportion of adenocarcinoma cases was higher in females than males (0.8% vs. 5.6%, p<0.001). Multivariate analysis indicated favorable overall survival for female patients (hazard ratio [HR], 0.685; 95% confidence interval [CI], 0.548-0.857) and patients with high body mass index (≥25 kg/m², HR, 0.432; 95% CI, 0.355-0.526), and in early tumor stage (Stage 4, HR, 12.684; 95% CI, 7.451-21.591). The 5-year overall survival (44.8% vs. 53.5%, p=0.016) and recurrence-free survival rates (74.0% vs. 84.3%, p=0.036) were higher in females than in males. We found significant sex differences in esophageal cancer among the Korean population, with female patients demonstrating distinct clinical characteristics and more favorable survival outcomes compared to male patients. These findings underscore the importance of considering sex-specific factors in the management and prognosis of esophageal cancer.

Association between C-reactive protein-albumin-lymphocyte index and overall survival in patients with esophageal cancer.

Esophageal cancer is an aggressive malignant tumor with poor prognosis, making early detection and treatment crucial. C-reactive protein-albumin-lymphocyte (CALLY) index is a comprehensive indicator which is involved in the process of metabolism, inflammation and immune reaction, and has been addressed to correlate with clinical outcomes in cancer patients. However, However, the evidence in esophageal cancer remains unclear. This study aims to investigate the association between CALLY index and overall survival of patients with esophageal cancer. This study includes the clinical characteristics of 518 patients with esophageal cancer from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) project, and evaluates the correlation between CALLY index and overall survival by COX regression analysis. Time-patient survival trends are verified using Kaplan-Meier method, and cubic spline function. Based on the results of multivariate Cox analysis, a nomogram showing 1, 2, 3, and 5-year survival rates is constructed. Calibration curve and decision curve analysis are used to evaluate the prediction accuracy and practical value of nomogram survival prediction. TNM staging of patients with esophageal cancer is determined according to the pathological examination results of the tumor and surrounding tissues, including the size and depth of the tumor (T), the involvement of lymph nodes (N), and the distant metastasis (M). Multivariate Cox regression analysis demonstrates that CALLY index (HR:0.967, 0.937-0.997, P<0.05), smoking (HR: 1.592, 1.064-2.380, P<0.05), TNM staging (HR: 1.595, 1.120-2.270, P<0.05) are independent prognostic factors for survival of patients with esophageal cancer. Patients with high CALLY index has the lower risk of death than those with low CALLY index (HR: 0.54, 0.36-0.80, P<0.05). The nomogram model including CALLY index shows better prediction ability than traditional TNM staging system. CALLY index is independently positive associated with overall survival in patients with esophageal cancer and nomogram model displays superiority over TMN staging in predicting overall survival.

A hypoxia-targeting and hypoxia-responsive nano-probe for tumor detection and early diagnosis.

Accurate imaging of tumor hypoxia in vivo is critical for early cancer diagnosis and clinical outcomes, highlighting the great need for its detection specificity and sensitivity. In this report, we propose a probe (HTRNP) that simultaneously has hypoxia-targeting and hypoxia-responsive capabilities to enhance the tumor hypoxia imaging efficiency. HTRNP was successfully prepared through the encapsulation of Pt(II)-tetrakis(pentafluorophenyl)porphyrin (PtPFPP), which exhibits hypoxia-dependent phosphorescence, within the amphiphilic block copolymer OPDMA-PF, which has hypoxia-targeting tertiary amine N-oxide moieties and hydrophobic perfluorobenzene ring structures, which highly improved the loading content and water solubility of PtPFPP. By combining targeting and response abilities toward hypoxic conditions, the HTRNP micelles efficiently accumulate in the tumor tissues and emit intense phosphorescence, thus enabling ultrasensitive detection of various tumor models, even of hundreds of cancer cells, indicating its promising potential for early cancer detection and phenotypic characterization.

Treatment initiation and completion among head and neck squamous cell carcinoma patients in Tanzania

Abstract Objective Few studies characterizing clinical outcomes of head and neck cancer (HNC) patients in sub-Saharan Africa report the proportion of patients who initiate and complete treatment, information integral to contextualizing survival outcomes. This retrospective cohort study describes HNC patients who presented to Muhimbili National Hospital and Ocean Road Cancer Institute in 2018, the highest-volume oncology tertiary referral centers in Tanzania. Logistic regression was applied to assess predictors of treatment initiation and completion. Results Among the 176 head and neck squamous cell carcinoma (HNSCC) patients, 34% (59) had no treatment documented, 34%(59) had documentation of treatment initiation but not completion, and 33%(58) had documentation of treatment completion based on the modalities started. Univariate logistic regression showed that late-stage disease was associated with increased odds of initiating treatment (OR 8.24, 95% CI 2.05–33.11, p = 0.003) and trends toward completing treatment (OR 7.41, 95% CI 0.90–60.99, p = 0.063). At last visit, 36.9%(65) were alive with a median follow up of 5.6 months (IQR 1.64—12.5 months). A large proportion of HNC patients who presented to MNH and ORCI did not initiate or complete treatment. These metrics are critical to contextualize care outcomes of HNC patients in resource-constrained health systems and develop interventions.

Circulating tumor DNA dynamics and clinical outcome in metastatic colorectal cancer patients undergoing front-line chemotherapy.

we tested whether ctDNA changes may be used to assess early response and clinical outcome in metastatic colorectal cancer (mCRC) patients undergoing front-line systemic anti-cancer therapy (SACT). 862 plasma samples were collected 4-weekly from baseline (BL) until disease progression in mCRC patients receiving front line SACT. ctDNA normalization was defined as ≥99% clearance after 1 month of therapy (Mo1) in the 3 variants with the highest allele frequency in BL ctDNA. 83 paired samples from 75 patients were available for analysis. 12 pairs (14.4%) showed no variants in either BL or Mo1. In the remaining 71 comparisons (65 patients), 37 (52.1%) showed ctDNA normalization at Mo1. Patients that cleared ctDNA had significantly longer overall (45.6 months) and progression-free survival (13.9 months) compared to non-normalized patients [OS= 22.6 months (Log-rank p = 0.01) and PFS= 10.7 months (Log-rank p = 0.036) respectively]. In addition, higher response rate was observed in patients with ctDNA clearance (72.9%) compared to non-normalized cases (38.2%). Longitudinal sequencing of at least four timepoints in pts with a PFS>10 months showed emerging variants in 47.8% of cases; in all these patients the trajectory of these new "outlier" variants appeared in stark contrast with the clinical-radiological course of disease and the trend in other mutations. ctDNA clearance represents an early indicator of benefit from SACT in mCRC patients; serial tracking of multiple variants is warranted to improve specificity and to avoid misleading information due to the emergence of mutations of unknown clinical significance.

The Effect of Pre-Biopsy Prostate MRI on the Congruency and Upgrading of Gleason Grade Groups Between Prostate Biopsy and Radical Prostatectomy

Introduction: Prostate biopsy results form the mainstay of patient care. However, there is often significant discordance between the biopsied histology and the ‘true’ histology shown on a radical prostatectomy (RP). Discordance in pathology can lead to the mismanagement of patients, potentially missing clinically significant cancer and delaying treatment. There have been many advancements to improve the concordance of pathology and more accurately counsel patients; most notably, the induction of pre-biopsy mpMRIs has become a gold standard to aid in triaging and identifying clinically significant cancers, and also to facilitate ‘targeted’ biopsies. Although there have been multiple reviews on MRI-targeted biopsies, upgrading remains an ongoing phenomenon. Aim: To assess the rates of prostate cancer upgrading and the clinical implication of upgrading on NCCN stratification. Methods: We conducted a retrospective audit of 2994 men with non-metastatic prostate cancer diagnosed between 2010 and 2019 who progressed to a radical prostatectomy within 1 year of diagnosis without alternative cancer treatment from the multi-institutional South Australia Prostate Cancer Clinical Outcomes Collaborative registry. The study compared the histological grading between the biopsies and radical prostatectomies of men with prostate cancer and the varying rates of upgrading and downgrading for patients with and without a pre-biopsy MRI. Data were also obtain on suspected confounding variables; age, PSA, time to RP, T-stage at diagnosis and RP, number of cores, number of positive cores, prostate size, tumour volume and procedure type. The results were assessed through cross tabulation and uni- and multi-variate logistic regression while adjusting for confounders. Results: Upgrading occurred in (926) 30.9% of patients and downgrading in (458) 15.3% of patients. In total, 71% (410/579) of grade group 1 and 24.9% (289/1159) of grade group 2 were upgraded following a radical prostatectomy. By contrast, 33.4% (373/1118) of patients without prebiopsy MRI were upgraded at RP compared to 29.5% (553/1876) of the patients who received a pre-biopsy MRI. When analysed on a uni-variate level, the inclusion of a pre-biopsy MRI demonstrated a statically significant decrease in upgrading of the patient’s pathology and NCCN risk stratification (p = 0.026, OR 0.83, CI 0.71–0.98) (p = 0.049, OR 0.82, CI 0.64–1.01). However, when adjusted for confounders, the use of an MRI did not maintain a statistically significance. Conclusions: When considering the multiple variables associated with tumour upgrading, a pre-biopsy MRI did not show a statistically significant impact. However, upgrading of Gleason Grade Group following a prostatectomy is an ongoing phenomenon which can carry significant treatment implications and should remain a consideration with patients and clinicians when making decisions around treatment pathways. More research is still required to understand and improve biopsy grading to prevent further upgrading from affecting treatment choices.

Clinical Characteristics, Management and Outcomes of Colitis-associated Colorectal Cancer and the Comparison to Sporadic Colorectal Cancer in Taiwan.

We explored the clinical characteristics, treatment, and outcomes of colitis-associated colorectal cancer and compared with sporadic colorectal cancer in Taiwan. In this retrospective study spanning 1987-2022, colitis-associated colorectal cancers diagnosed according to endoscopic and pathological reports from 14 tertiary centers were reported to our cohort. Clinical demographics, endoscopic findings, histological results, treatment modalities, and outcomes were analyzed. Sporadic colorectal cancer data were retrieved from the Cancer Registry Annual Report, Ministry of Health and Welfare, Taiwan. We enrolled 65 colitis-associated colorectal cancer patients (median age: 56 years; male: 66.2%). Distal colon was the most common tumor location (41.5%). Of ulcerative colitis patients, 77.2% had extensive colitis and 76.5% had Mayo endoscopic subscores of ≥2. Moreover, 50% of lesions were nonpolypoid with indistinct borders in 66.7%. Signet-ring cell subtype consisted 12.3%. Surveillance colonoscopy adherence was 78.4%, yet 51.3% interval cancers occurred. Disease stage 0-4 distribution was 15%, 20%, 13.3%, 20%, and 31.7%, respectively. Endoscopic resection was feasible for 14%, while 67.7% required surgery. During follow-up (median: 21.5 months), we recorded 23.2% recurrence and 34.5% mortality. Lesions with indistinct borders were associated with adverse outcomes (adjusted odds ratio = 11.5 [1.35-98.16]). Colitis-associated rectal cancers, diagnosed later (p < 0.001), had worse outcomes than sporadic rectal cancers. This is the largest Asian colitis-associated colorectal cancer cohort study, emphasizing the need for stringent disease control, improving detection and reducing interval cancers. Signet-ring cell subtype was prevalent. Rectal colitis-associated cancers were diagnosed later with poorer outcomes then sporadic rectal cancers.

Associations between MRI radiomic phenotypes and clinical outcomes in endometrial cancer: Implications for preoperative risk stratification.

This study aimed to investigate the correlation between imaging phenotypes of endometrial cancer (EC) and clinical, pathologic, and molecular characteristics, as well as disease-free survival (DFS). The clinical, pathologic, and molecular characteristics, along with MRI radiomics features, of 356 patients with EC were collected retrospectively. The patients were divided into 2 groups based on radiomics features using unsupervised machine learning. The obtained characteristics and DFS of patients were compared between the various imaging phenotypes. The lesions with deep myometrial invasion (DMI), lymphovascular space invasion (LVSI), cervical stromal invasion (CSI), lymph node metastasis, aggressive histologic type, advanced postoperative International Federation of Gynecology and Obstetrics (FIGO) stage, overexpression of p53, and absent expression of estrogen receptor or progesterone receptor were associated with poor DFS. Two clusters were identified and defined as imaging phenotype 1 and 2, respectively. Compared with phenotype 2, phenotype 1 exhibited a higher correlation with DMI (33.7% vs 13.0%), LVSI (23.8% vs 9.2%), CSI (16.3% vs 3.8%), aggressive histologic type (36.0% vs 17.4%), and advanced FIGO stage (IB or higher, 43.6% vs 22.3%) (p<0.001). The incidence of p53 overexpression was higher in phenotype 1 than in phenotype 2 (20.2% vs 8.5%, p=0.022). Survival analysis exhibited a higher risk of poor DFS in phenotype 1 than in phenotype 2 (log-rank p=0.002). EC imaging phenotypes identified through MRI radiomics features were associated with pathologic, molecular characteristics, and DFS, suggesting potential for preoperative risk stratification.

Post-prostatectomy Magnetic Resonance-guided Radiotherapy on a 1.5 Tesla Magnetic Resonance Integrated Linear Accelerator: Feasibility, Toxicity, and Preliminary Clinical Outcomes.

This study aimed to prospectively investigate magnetic resonance (MR)-guided radiotherapy (MRgRT) for post-prostatectomy prostate cancer and report preliminary clinical outcomes. All included patients underwent salvage or adjuvant adaptive MRgRT on a 1.5T MR integrated linear accelerator (MR-LINAC). Gastrointestinal and genitourinary toxicities were assessed. The primary endpoint was the progression-free survival (PFS) rate estimated by Kaplan-Meier (KM) survival analysis. A progression event was defined as the first occurrence of biochemical failure, radiological progression, or death. Secondary endpoints were biochemical failure-free survival (bFFS) rate, radiological PFS (rPFS) rate, and ≥G2 adverse events. Thirty post-prostatectomy patients were enrolled and followed (median follow-up: 32.0 months; 3.0-48.1 months). Three patients had biochemical failure during follow-up. One patient developed pelvic node metastases. All patients were alive. The estimated PFS rates were 96.4% (95% confidence interval [95%CI]: 89.8%-100.0%) at 2 years and 78.8% (95%CI: 61.3%-100%) at 3 years. The estimated bFFS rates were 96.4% (95%CI: 89.8%-100%) /86.6%(95%CI: 73.4%-100%) at 2/3 years, respectively. The corresponding rPFS rates were 100% at 2 years and 92.3% (95%CI: 78.9%-100%) at 3 years, respectively. There was only one acute G2 GI adverse event (1/30, 3.33%) of abdominal pain occurred. Two late G2 events (one rectal bleeding and one urinary frequency) were scored (2/30, 6.67%). No ≥G3 events were observed. Our findings suggest the feasibility, excellent patient tolerance, and encouraging efficacy of post-prostatectomy MRgRT, extending our knowledge of the clinical outcomes of MRgRT and serving as a benchmark for future investigation.

Innovative approaches in stem cell therapy: revolutionizing cancer treatment and advancing neurobiology - a comprehensive review.

Stem cell therapy represents a transformative frontier in medical science, offering promising avenues for revolutionizing cancer treatment and advancing our understanding of neurobiology. This review explores innovative approaches in stem cell therapy that have the potential to reshape clinical practices and therapeutic outcomes in cancer and neurodegenerative diseases. In this dynamic and intriguing realm of cancer research, recent years witnessed a surge in attention toward understanding the intricate role of mesenchymal stem cells (MSCs). These cells, capable of either suppressing or promoting tumors across diverse experimental models, have been a focal point in the exploration of exosome-based therapies. Exosomes released by MSCs have played a pivotal role, in unraveling the nuances of paracrine signaling and its profound impact on cancer development. Recent studies have revealed the complex nature of MSC-derived exosomes, showcasing both protumor and antitumor effects. Despite their multifaceted involvement in tumor growth, these exosomes show significant promise in influencing both tumor development and chemosensitivity, acting as a pivotal factor that increases stem cells' potential for medicinal use. Endogenous MSCs, primarily originating from the bone marrow, exhibited a unique migratory response to damaged tissue sites. The genetic modification of stem cells, including MSCs, opened avenues for the precise delivery of therapeutic payloads in the milieu around the tumor (TME). Stem cell therapy offers groundbreaking potential for treating neurodegenerative and autoimmune disorders by regenerating damaged tissues and modulating immune responses. This approach aims to restore lost function and promote healing through targeted cellular interventions. In this review, we explored the molecular complexities of cancer and the potential for breakthroughs in personalized and targeted therapies. This analysis offers hope for transformative advancements in both cancer treatment and neurodegenerative disorders, highlighting the promise of precision medicine in addressing these challenging conditions.

Increased Early-Mortality in Children With Solid Tumors During the COVID-19 Pandemic in a Middle-Income Country.

Measures to control COVID-19 transmission disrupted childhood cancer care. Data on the effects of the COVID-19 pandemic on childhood cancer mortality are lacking. This study describes the impact of the pandemic on childhood cancer early-mortality (≤ 24 months). A multicenter prospective cohort was conducted in 10 Colombian cities. Children with newly diagnosed cancer registered in the Childhood Cancer Clinical Outcomes Surveillance System (VIGICANCER) were included. Our primary outcome was cumulative mortality at 3, 6, 12, and 24 months. The exposed cohort (EC = March 25, 2020-December 31, 2021) was compared with a historic cohort (HC = January 1, 2017-March 24, 2020). Covariates included sociodemographics, place of residence, health insurance type, and tumor classification. The cohort included 4124 children, comprised of 1627 children in the EC and 2497 children in the HC. Hematolymphoid, central nervous system, and extracranial solid tumors represented 57%, 15%, and 28% of patients, respectively. Participants' median age was 6.7 years (IQR, 3.2-11.3), 54% were male, 7% were Afro-descendant, and 47% had public insurance. In the EC, the 6-month and 24-month mortality adjusted hazard ratio (aHR) in children with solid tumors was 1.7 (95% CI, 1.1-2.7) and 1.3 (95% CI, 1.0-1.7), respectively, and in children with bone tumors 4.0 (95% CI, 1.2-13.0) and 2.1 (95% CI, 1.2-3.6), respectively. These associations persisted after accounting for metastatic disease. Six-month mortality aHRs for retinoblastoma, bone tumors, and soft tissue sarcomas due to progressive disease were 4.3 (95% CI, 1.3-14.5), 4.0 (95% CI, 1.4-11.3), and 5.4 (95% CI, 2.2-13.5), respectively. In the EC, the adjusted odds ratio (aOR) for metastatic solid tumors vs. nonmetastatic was 1.4 (95% CI, 1.0-1.8) and in children with retinoblastoma and public insurance the 24-month mortality aHR was 4.9 (95% CI, 1.1-21.7). We observed increased early-mortality for solid tumors, particularly bone tumors and retinoblastoma, likely attributed to more advanced-stage presentation and loss of treatment effectiveness due to healthcare disruptions. Early-mortality was higher in patients with public insurance, a vulnerable population that warrants attention.