Clinical Tumor Research Articles

Successful Management of Incompletely Resected Transitional Cell Carcinoma with Sorafenib Tosylate in a Dog.

Most urinary bladder (UB) tumors are malignant, and transitional cell carcinoma (TCC) is the most common neoplasm affecting the UB in dogs. Sorafenib may be a potential therapeutic agent for canine TCC. A 12 yr old spayed female Maltese dog weighing 3.6 kg and with a history of hematuria was referred for a suspected UB tumor. Abdominal ultrasonography revealed a UB mass attached to the cranioventral wall. The remaining abdominal examinations, including that of the lymph nodes, were unremarkable. Ultrasound-guided traumatic catheterization of the UB mass was performed, and the cytological evaluation of the UB mass indicated TCC. Excision was performed by partial cystectomy, and histopathology confirmed TCC, although the tumor had infiltrated the surgical margins. A chemosensitivity assay was conducted using tissue from the excised tumor. Sorafenib tosylate, a tyrosine kinase inhibitor, showed the greatest effect in the chemosensitivity assay. Therefore, adjuvant chemotherapy with sorafenib tosylate and piroxicam was administered postoperatively. The dog lived without any clinical signs, including hematuria or tumor relapse, for more than 2 yr after the surgery. This is the first report of successful long-term management of TCC with sorafenib tosylate in a dog.

Natural diterpene carrier-free hydrogel enhances antigen presentation and intensifies T cell activation for tumor immunotherapy

Although immunotherapy has revolutionized cancer treatment, the low immunogenicity, insufficient T cells intratumoral infiltration and defective antigen presentation in the “cold” tumor microenvironment limit its clinical application. To address this challenge, enlightened by the clinical combined application of antitumor herb medicines, we developed a carrier-free hydrogel KEEM by integrating multiple natural active lipophilic components with manganese ions into a natural co-assembled ternary system. The KEEM hydrogel induced the formation of hydroxyl radicals by Fenton-like reactions, leading to apoptosis, while simultaneously inducing tumor cell ferroptosis through the system xc−-GSH-GPX4 axis. Subsequent release of damage-associated molecular patterns (DAMPs) proved the emergence of immunogenic cell death (ICD). Additionally, manganese ions could directly activate the cGAS-STING pathway, further amplifying the immunostimulatory effects. This synergistic effect promoted dendritic cell maturation thus enhancing antigen presentation, and mediating the change of tumor microenvironment (TME) from “cold” to “hot”. In hepatoma ascites and melanoma models, KEEM combined with immune checkpoint blockade and adoptive T cell therapy respectively demonstrated promising anti-tumor effects in vivo, meanwhile showing excellent biocompatibility and biosafety. Thus, the combination of this multi-diterpenoids carrier-free hydrogel with immunotherapy offers a new strategy for clinical immune-refractory tumor treatment.

Development of a web-based tool for estimating individualized survival curves in glioblastoma using clinical, mRNA, and tumor microenvironment features with fusion techniques.

Glioblastoma (GBM), one of the most common brain tumors, is known for its low survival rates and poor treatment responses. This study aims to create a robust predictive model that integrates multiple feature types, including clinical data, RNA expression, and tumor microenvironment data, using fusion techniques to enhance model performance. We obtained data from the SEER database to assess the impact of nine demographic and clinical features on the survival of 58,495 GBM patients and built predictive machine learning models. Additionally, mRNA expression data from 600 GBM patients from TCGA, CGGA, and GEO were analyzed. We used Cox regression and LASSO to create a gene signature, which was compared against 13 published signatures for accuracy. Twenty-one machine learning models were applied to predict survival at multiple time points. Finally, we integrated multiple feature types using fusion techniques and developed a Shiny app to provide survival predictions for GBM patients. Using the SEER database, we constructed machine learning models based on nine clinical variables: age, gender, marital status, race, tumor site, laterality, surgery, chemotherapy, and radiation therapy. The best-performing model achieved AUC values of 0.775, 0.728, 0.692, and 0.683 for predicting survival at 6, 12, 18, and 24months in the testing cohort. In the merged TCGA, CGGA, and GEO cohorts, we identified 11 genes to develop predictive models. These 11 genes outperformed 13 other published gene signatures in predicting the prognosis of GBM. When incorporating mRNA features, tumor microenvironment features, and clinical variables into the fusion models, the AUC values for predicting survival at 6, 12, 18, and 24months were 0.641, 0.624, 0.655, and 0.637, respectively. A user-friendly tool for predicting the survival curve of individual GBM patients is available at https://zzubioinfo.shinyapps.io/mlGBM/ . Our study provides a web-based tool that includes two modules: one for predicting survival curves using only clinical variables, and another that integrates multiple feature types for more comprehensive predictions.

Alginate/chitosan-based hemostatic microspheres loaded with doxorubicin liposomes for postoperative local drug delivery in solid tumor.

In clinical solid tumor treatment, intraoperative bleeding, compromised postoperative recovery, and increased non-specific toxicity from chemotherapy are always challenges. To address these limitations, we developed and well characterized novel alginate/chitosan-based hemostatic microspheres loaded with doxorubicin liposomes. The multifunctional microspheres exhibited optimal drug loading capacity and excellent drug encapsulation efficiency. Remarkably, this unique structural composition enhanced the hemostatic performance by improving their swelling and adhesion properties, surpassing those of commercial hemostatic microspheres CELOX® in both rat tail amputation and hepatic injury models. In a tumor recurrence model, SCs-lip microspheres, designed with a multi-release in situ drug delivery system, achieved sustained release of doxorubicin over an extended period, effectively reducing its toxic side effects while enhancing therapeutic efficacy. Biocompatibility experiments further validated the safety profile of this multifunctional materials. The development of this drug delivery system presents a promising opportunity to bridge the "treatment gap" between solid tumor resection surgery and chemotherapy, offering a potentially transformative approach for the application of anti-tumor drugs.

PEGylated BODIPY Photosensitizer for Type I Dominant Photodynamic Therapy and Afterglow Imaging.

Type I photodynamic therapy (PDT) exhibits outstanding therapeutic effects in hypoxic environments in tumors, but the design of type I photosensitizers (PSs), especially those with simple structures but dramatic properties, remains a challenge. Herein, we report a design strategy for developing type I PSs in one molecule with afterglow luminescence. As a proof concept, a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) PS (BIP) bearing water-soluble poly(ethylene glycol) (mPEG550) chains is synthesized, and BIP can self-assemble into nanoparticles (BIPNs). Interestingly, BIPNs exhibit an O2•--triggered afterglow luminescence, which is scarce, especially for BODIPY derivatives. BIPNs demonstrate outstanding type I dominant PDT at an ultralow dose under both hypoxic and normoxic environments, which can significantly inhibit tumor growth under irradiation. This work highlights a high-performance PS with afterglow luminescence and excellent PDT effects, underscoring the significant potential of versatile PSs in clinical tumor theranostics.

Can Ki-67 serve as a suitable marker to indicate the necessity of staging diagnostics in cases of low-risk breast cancer?

For many years, staging tests have not been routinely employed for low-risk early breast cancer (EBC). However, the role of Ki-67 in determining the need for staging tests in low-risk EBC remains unclear. Our study aimed to assess the number and types of staging diagnostics, additional imaging, false-positive results, and rate of distant metastases in low-risk EBC with low and high Ki-67 (< / ≥ 25%). This is a retrospective, single institution cohort study. All patients with newly diagnosed low-risk breast cancer at the University Medical Center in Freiburg in 2017 and 2021 were included. Low-risk was defined as clinical tumor stage T1/2, node negative (N0), hormone receptor positive, HER2 negative, asymptomatic EBC. Information on demographics, clinical and pathological characteristics, as well as number and type of performed staging diagnostics was obtained. Rate and type of additional imaging or follow-up diagnostics due to suspicious findings was analyzed. The patients were divided into two groups (Ki-67 < and ≥ 25%) and rates of distant metastases, performed staging diagnostics and false positive rates were compared. A total of 189 patients with low-risk EBC were identified, with 54% (n = 102) having Ki-67 < 25% and 46% (n = 87) having Ki-67 ≥ 25%. Risk for distant metastases was 0% in Ki-67 < 25% and 1.1% in patients with Ki-67 ≥ 25% (p = 0.46). Due to suspicious findings in the initial staging diagnostic, additional imaging was required for 11.8% (n = 12) of patients with Ki-67 < 25% compared to 19.5% (n = 17) of patients with Ki-67 ≥ 25% (p = 0.16). False positive rates did not differ significantly between the two groups (7.6% in Ki-67 < 25% vs. 9.8% in Ki-67 ≥ 25%; p = 0.55). Distant metastases are rare in low-risk EBC. All in all, staging diagnostics should not be routinely employed in this patient population. Only patients with high Ki-67 developed distant metastases. In these cases, staging diagnostics may be discussed with the patient.

A dosimetric and robustness analysis of proton arc therapy with early energy layer and spot assignment for lung cancer versus conventional intensity modulated proton therapy.

Intensity Modulated Proton Therapy (IMPT) faces challenges in lung cancer treatment, like maintaining plan robustness for moving tumors against setup, range errors, and interplay effects. Proton Arc Therapy (PAT) is an alternative to maintain target coverage, potentially improving organ at risk (OAR) sparing, reducing beam delivery time (BDT), and enhancing patient experience. We aim to perform a systematic plan comparison study between IMPT and energy layer (EL) and spot assignment algorithm - Proton Arc Therapy (ELSA-PAT) to assess its potential for lung cancer treatment. A total of 14 Lung ELSA-PAT plans were compared retrospectively with IMPT plans. 4D worst-case minimax robust optimization was performed, including 84 scenarios (3%, 3 mm). Dosimetry assessment included target (clinical tumor volume [CTV]) and important OARs, on nominal and worst-case scenarios. Most relevant normal tissue complication probabilities (NTCP), target coverage robustness against interplay effect, and BDT were evaluated. CTV D95% and D98% showed no significant difference in comparison. PAT demonstrated better conformality by 66% (p = 0.00012) but delivered a higher heart mean dose (HMD, 23%). There was a 2% increase in NTCP 2-year mortality risk with PAT. Total BDT was comparable among techniques. IMPT was more robust than PAT against interplay effect, considering both D1% (1.0 ± 0.8 Gy vs 1.1 ± 1.4 Gy) and D98% bandwidths (0.9 ± 0.9 Gy vs 1.1 ± 1.3 Gy). Both techniques provide a similar level of dose coverage to the target volume. Although PAT improved dose conformality, higher HMD translated into increased heart toxicity, presumably due to chosen planning methodology and OAR proximity to target. Increased ELs and spots raised PAT BDT, although it could improve daily treatment workflow.

Nomogram for the Pathological Complete Response After Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer Patients.

No validated instrument currently exists to predict neoadjuvant chemotherapy (NAC) response in muscle-invasive bladder cancer (MIBC) patients. We aim to develop and validate a nomogram based on clinicopathological factors for predicting who would benefit most from NAC. Between January 2016 and April 2023, 361 consecutive MIBC patients treated with NAC were enrolled in the study. Two hundred sixty patients at the Hu Nan institution comprised the development cohort. The validation cohort (91 patients) was from the Xiang Hua center. Patient clinicopathologic information was documented. Using regression coefficients, a predictive model was constructed using multivariate logistic regression. The likelihood ratio test with Akaike's information criterion was then used as the ending rule for backward stepwise selection. This predictive model's efficacy was evaluated for discrimination, calibration, and clinical utility. Predictors of this model included the origin of MIBC, pathological tumor type, clinical tumor stage, and tumor size. In the validation cohort, the model demonstrated good discrimination with an AUROC of 0.7221 (P < 0.001) and calibration (Unreliability test, P = 0.580). In addition, decision curve analysis revealed that the model was clinically beneficial. This study indicated that primary MIBC, pure UC pathological type, lower clinical tumor stage, and maximum tumor diameter <3 cm were significant predictors of ypCR in MIBC patients after NAC. This nomogram may contribute to the preciousadministration of NAC and the avoidance of chemotherapy toxicity and delayed RC.

Clinical and Pathological Characteristics of Bladder Cancer in Patients Aged 18–45 Undergoing Transurethral Resection of Bladder Tumor

Background and Objectives: Bladder cancer in patients under 45 is poorly characterized and rarely described, with variabilities in clinical outcomes and tumor properties. Our study aimed to elucidate the clinical and pathological features and outcomes of bladder cancer in this younger demographic to better inform management strategies. Materials and Methods: We conducted a retrospective analysis at the Urology Department of “Pius Brînzeu” County Emergency Clinical Hospital in Timișoara, Romania, on 60 patients aged 18–45 who underwent transurethral resection of bladder tumor (TURBT) during a 9-year period. Results: The cohort had a mean age of 38.5 ± 5.6 years with a male predominance (70%). Most tumors were non-muscle-invasive (NMIBC; 80%), with 16.7% being papillary urothelial neoplasms of low malignant potential (PUNLMP), 50% stage pTa, and 30% stage pT1. High-grade tumors were present in 43.3% of the patients. Recurrence occurred in 40% of the patients, while progression was observed in 16.7%. The 3-year overall survival rate was 93.3%, and the progression-free survival rate was 83.3%. Patients with high-grade tumors had a significantly higher recurrence rate (61.5% vs. 23.5%, p = 0.003) and lower survival rates compared to those with low-grade tumors. Conclusions: Young patients predominantly present with low-to-intermediate-stage tumors, yet a significant portion exhibit high-grade tumors associated with poorer outcomes. These findings suggest that while bladder cancer in younger patients tends to be less invasive, aggressive follow-up and treatment are crucial in those with high-grade tumors.

A novel scoring system proposal to guide surgical treatment indications for high grade gliomas in elderly patients: DAK-75.

High-grade gliomas are the most prevalent neurooncological desease in adults, their incidence increases with age, peaking in the seventh decade. This paper aims to address how to select patients for surgical resection by identifying pre-surgical predictors of 12-month mortality in newly diagnosed HGG patients aged ≥ 75years. A prognostic score will be proposed to guide surgical decisions based on expected survival. Retrospective observational single-center cohort study was carried out at the "Città della Salute e della Scienza-Molinette" University Hospital in Turin, Italy. All consecutive patients aged ≥ 75years newly diagnosed with HGG were included, regardless of whether they underwent surgical resection. Clinical, radiological, histological and molecular data were collected.Variables potentially available at the time of diagnosis were considered to develop a multivariable logistic regression predictive model, with 12-months overall survival as the dependent variable. 102 patients aged 75years or older received a new diagnosis of high-grade glioma, of whom 68 underwent surgical resection. Patients undergoing surgery were slightly younger (76.9 vs 79.0years, p = 0.007) and had better performance status (median KPS 80 vs 70). Most tumors undergoing surgery were localized in cortical or subcortical non-motor areas (p < 0.001) and less frequently deep-seated (p = 0.023) or multifocal (p < 0.001). A predictive model, the DAK-75 score, was developed: the AUROC of the final model was 0.822 (95% CI 0.741-0.902). The score includes clinical presentation, tumor location, and KPS, ranging from 0 to 20, categorizing risk scores into low-risk and high-risk groups (< or > 8). Higher scores corresponded to fewer surgical patients and higher one-year mortality rates (92.2% vs 47.1%, p < 0.001). DAK-75 score may represent a valuable tool in the decision-making process for neurosurgical intervention in elderly patients diagnosed with HGG. Further studies are needed to externally and prospectively validate the scoring system.

Nanomaterials for enhanced X‐ray‐triggered cancer therapy: Progress and prospects

AbstractX‐rays, a form of ionizing radiation with high energy and significant penetration capability, are commonly used in clinical tumor treatment through radiotherapy. Despite their widespread use, optimizing X‐ray efficacy remains a critical challenge due to issues such as radiation resistance and damage to surrounding health tissues. Recent advancements in nanotechnology have introduced new opportunities and challenges in cancer diagnosis and treatment. This review summarizes the latest progress in nanomaterials for X‐ray‐triggered cancer therapy, highlighting their various advantages such as targeted delivery, reduced side effects, and enhanced therapeutic efficacy. We examine how nanomaterials, including metals, metal oxides, metal sulfides, metal fluorides, rare earth oxides, cluster compounds, metal‐organic frameworks, and nanohybrids, enhance the effectiveness of X‐ray‐triggered treatments. Furthermore, we address the current challenges and future prospects of efficient X‐ray‐triggered cancer therapy, aiming to provide a comprehensive overview for researchers and clinicians in the field.

A Tumor-Homing Nanoframework for Synergistic Microwave Tumor Ablation and Provoking Strong Anticancer Immunity Against Metastasis.

Microwave thermotherapy (MT) is a clinical local tumor ablation modality, but its applications are limited by its therapeutic efficacy and safety. Therefore, developing sensitizers to optimize the outcomes of MT is in demand in clinical practice. Herein, we engineered a special nanoframework (i.e., FdMI) based on a fucoidan-decorated zirconium metal-organic framework incorporating manganese ions and liquid physisorption for microwave tumor ablation. The monodisperse nanoframework exhibited both microwave thermal effects and microwave dynamic effects, which could effectively kill cancer cells by efficient intracellular drug delivery. Through fucoidan-mediated targeting of P-selectin in the tumor microenvironment (TME), the FdMI effectively accumulated in tumor regions, leading to significant eradication of orthotropic triple-negative breast cancer (TNBC) and aggressive Hepa1-6 liver tumors by the synergistic effects of microwave thermotherapy/dynamic therapy (MT/MDT). The eradication of primary tumors could activate systemic immune responses, which effectively inhibited distant TNBC tumors and lung metastasis of Hepa1-6 liver tumors, respectively. This work not only engineered nanoparticle sensitizers for tumor-targeted synergistic MT/MDT but also demonstrated that nanocarrier-based microwave tumor ablation could stimulate antitumor immunity to effectively inhibit distant and metastatic tumors, demonstrating the high potential for effectively managing advanced malignant tumors.

A single-center case study series assessing the effect of selumetinib use in patients with neurofibromatosis-related plexiform neurofibromas

Abstract Background Neurofibromatosis type 1 (NF1) is a common genetic disorder of phenotypic variability with age-dependent penetrance. This study describes the diagnosis, clinical characterization, management, and outcomes of a large patient cohort with plexiform neurofibroma (PN) treated with selumetinib in a real-world clinical setting. Methods This single-center observational study consecutively enrolled patients with NF1-PN treated with selumetinib from April 2018 to April 2023. Data on clinical features, tumor types and locations, and results from genetic tests were recorded at baseline; details of disease management with selumetinib and surgical intervention and disease evolution including imaging data and evaluations of pain and function were documented. Results Overall, 54 patients with a median age (range) of 16.4 (4.5–58.0) years were enrolled. Most had cutaneous manifestations (88.9%), including cutaneous neurofibromas and PN. Patients underwent [18F]fluorodeoxyglucose (FDG)-PET/CT imaging before treatment to rule out malignant lesions. Initial evaluations included directed MRI, which facilitated future comparisons and allowed for the assessment of PN resectability. Pharmacological treatment with selumetinib (with surgery, without surgery) resulted in the following proportion of patients achieving stable disease (58.8%, 54.3%), partial response (29.4%, 28.6%), and improved pain (58.8%, 37.1%), deformity (17.6%, 20.0%), and functional (17.6%, 20.0%) outcomes, respectively. Conclusions Results from this study demonstrate that NF1-PN can be managed effectively with selumetinib with surgical intervention in some patients. Most patients achieved tumor stability and improved symptom control, and the majority of patients continue under treatment. Effective diagnosis and management were achieved through individualized utility of FDG-PET/CT and MRI imaging and targeted resource allocation.

Circulating miR-18a and miR-532 Levels in Extrahepatic Cholangiocarcinoma.

Background: Cholangiocarcinoma (CCA) is a highly aggressive cancer of the bile ducts with a poor prognosis and limited diagnostic markers. This study aims to investigate the potential of miR-18a and miR-532 as biomarkers for CCA by exploring their correlations with clinical parameters and traditional tumor markers such as CA19.9, CEA, and AFP. Methods: This study involved a cohort of patients diagnosed with CCA. Serum levels of miR-18a and miR-532 were measured and analyzed in relation to various clinical parameters, including age, tumor markers, and histological features. Results: Serum levels of miR-18a and miR-532 were upregulated in patients with extrahepatic cholangiocarcinoma (eCCA) compared to healthy controls (p < 0.05). MiR-18a and miR-532 levels were correlated with each other (p = 0.011, Spearman's rho = 0.482) but showed no significant correlation with age or traditional tumor markers (CA19.9, CEA, AFP). No significant differences in miR-18a and miR-532 levels were observed concerning tumor localization or histological grading. For predicting tumor resectability, miR-532 at a cut-off point of 2.12 showed a sensitivity of 72.73%, specificity of 81.25%, and an AUC of 71.3%, while miR-18a, at a cut-off of 1.83, had a sensitivity of 63.64%, specificity of 75%, and an AUC of 59.7%. ROC curve analysis suggested moderate diagnostic potential for miR-18a and miR-532, with AUC values of 0.64 and 0.689, respectively. Conclusions: Although miR-18a and miR-532 showed significant upregulation in eCCA patients compared to healthy controls, they did not demonstrate significant associations with key clinical parameters, limiting their effectiveness as standalone diagnostic biomarkers. Further research involving larger, multi-center cohorts and additional molecular markers is necessary to validate these findings and explore the broader diagnostic potential of miRNAs in CCA.

Nationwide questionnaire survey on pediatric pancreatic tumors in Japan.

Pediatric pancreatic tumors are rare and account for < 0.1% of all childhood cancers. The primary treatment for pancreatic tumors is surgical resection. However, because of the lack of knowledge regarding pediatric pancreatic tumors, no comprehensive treatment plans for pediatric pancreatic tumors have been developed. To compared the clinical features, treatment methods, and prognosis of pediatric pancreatic tumors in Japan with those in other countries. Questionnaires were sent to 213 pediatric surgical units in Japan. Pancreatic tumors that were not surgically treated were excluded from the survey. The primary survey investigated the number of patients aged 0-18 years who underwent pancreatic tumor surgery and the type of tumors managed during the 22-year study period (from January 1, 2000 to December 31, 2021) by post card. The secondary survey assessed the clinical images, treatment methods, and tumor outcomes via email. The primary survey enrolled 228 patients. In the secondary survey, 213 patients were eventually enrolled. The most common type of pancreatic tumor was solid pseudopapillary neoplasm (SPN) [n = 164 (77.0%)], followed by pancreatoblastoma [n = 16 (7.5%)], pancreatic endocrine tumor [n = 14 (6.6%)], non-epithelial tumor [n = 9 (4.2%)], pancreatic tumor [n = 7 (3.3%)], and metastatic pancreatic tumor [n = 3 (1.4%)]. Overall, 123 (57.7%) patients underwent distal pancreatectomy, of whom 49 underwent laparoscopic surgery. Forty-four (20.7%) patients underwent enucleation, of whom eight underwent laparoscopic surgery. Thirty-two (15.0%) patients underwent pancreaticoduodenectomy, of whom one underwent laparoscopic surgery. All patients with SPN, including those with distant metastases and recurrent disease, survived. SPN was more common in Japan than in other countries. Regardless of the histological type, resection is the most effective treatment for pediatric pancreatic tumors.

Research progress of tumor-associated macrophages in immune checkpoint inhibitor tolerance in colorectal cancer.

The relevant mechanism of tumor-associated macrophages (TAMs) in the treatment of colorectal cancer patients with immune checkpoint inhibitors (ICIs) is discussed, and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies. As a class of drugs widely used in clinical tumor immunotherapy, ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system. The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly. The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs. ICIs can regulate the phenotypic function of TAMs, and TAMs can also affect the tolerance of colorectal cancer to ICI therapy. TAMs play an important role in ICI resistance, and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.

ELAVL1 regulates glycolysis in nasopharyngeal carcinoma cells through the HMGB3/β-catenin axis

BackgroundThe role of ELAVL1 in the progression of various tumors has been demonstrated. Our research aims to investigate how ELAVL1 controls the glycolytic process in nasopharyngeal carcinoma cells through the HMGB3/β-catenin pathway.MethodsThe expression of ELAVL1 was detected in clinical tumor samples and nasopharyngeal carcinoma cell lines. A subcutaneous tumor model was established in nude mice to investigate the role of ELAVL1 in tumor progression. The relationship between HMGB3 and ELAVL1 was validated by RNA pull down and RIP assays. TOPFlash/FOPFlash reporter assay was used to detect β-catenin activity. Assay kits were utilized to measure glucose consumption, lactate production, and G6PD activity in nasopharyngeal carcinoma cells. Western blot was conducted to detect the expression of glycolysis-related proteins. The glycolytic capacity was analyzed through extracellular acidification rate (ECAR).ResultsIn both clinical samples and nasopharyngeal carcinoma cell lines, the expression levels of ELAVL1 mRNA and protein were found to be upregulated. Knockdown of ELAVL1 significantly inhibited the in vivo proliferation of nasopharyngeal carcinoma and suppressed the glycolytic capacity of nasopharyngeal carcinoma cells. ELAVL1 interacts with HMGB3, leading to an increase in the stability of HMGB3 mRNA. Overexpression of HMGB3 elevated the reduced β-catenin activity caused by sh-ELAVL1 and reversed the inhibitory effect of sh-ELAVL1 on cellular glycolytic capacity. Treatment with β-catenin inhibitor (FH535) effectively suppressed the promotion of glycolytic capacity induced by HMGB3 overexpression.ConclusionsELAVL1 promotes glycolysis in nasopharyngeal carcinoma cells by interacting with HMGB3 to stabilize HMGB3 mRNA, thereby activating β-catenin pathway. Therefore, targeting the ELAVL1-HMGB3-β-catenin axis has the potential to be a novel approach for treating nasopharyngeal carcinoma.

[18F]FDG whole-body PET-MR including an integrated breast MR protocol for locoregional and distant staging in breast cancer patients—a feasibility study

PurposeTo investigate in a feasibility study the combination of [18F]FDG whole-body (WB) positron emission tomography-magnetic resonance (PET-MR), including an integrated breast MR within a single protocol for locoregional and distant staging in breast cancer patients.MethodsConsecutive patients with breast cancer diagnoses according to conventional imaging modalities (full-field digital mammography (FFDM) and ultrasound (US)) were prospectively included. All patients underwent [18F]FDG WB PET-MR, including an integrated dedicated breast MR (prone position) and WB PET-MR (supine position) protocol. Results of [18F]FDG WB PET-MR, including integrated breast MR, versus conventional imaging modalities were compared.ResultsFrom April 2021–April 2022, 28 patients were included. On conventional imaging, cT1-2 breast cancer was present in 22 (FFDM) and 23 (US) out of 28 patients. With regard to clinical nodal status, eight patients were considered cN0, eighteen cN1 (1-3 suspicious lymph nodes), and two patients were cN2 (four suspicious axillary lymph nodes/internal mammary lymph node metastasis). [18F]FDG WB PET-MR, including an integrated breast MR protocol, upstaged clinical tumor status in two patients and clinical nodal status in nine patients according to both [18F]FDG WB PET-MR and breast MR findings. In addition, distant metastases were detected in three patients (liver/bone), and another patient was diagnosed with a synchronous primary tumor (lung cancer).Conclusion[18F]FDG WB PET-MR, including an integrated breast MR within a single protocol in breast cancer patients, is feasible and provides a promising new approach in breast cancer patients with regard to locoregional and distant staging.Critical relevance statement[18F]FDG whole-body PET-MR, including an integrated breast MR protocol, is feasible and allows locoregional and distant staging within a single imaging exam in breast cancer patients.Key Points[18F]FDG PET-MR allows the combination of breast MR and whole-body staging.Therefore, a single protocol of whole-body [18F]FDG PET-MR, including an integrated breast MRI, is investigated.[18F]FDG PET-MR, including an integrated breast MR is feasible and can be considered in daily clinical practice.Graphical

A retrospective comparison of induction chemoimmunotherapy versus chemotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy in stage III non-small cell lung cancer.

Patients with locally advanced non-small cell lung cancer (LA-NSCLC) usually bear high tumor burden and are not tolerated well to concurrent chemoradiation therapy (CRT) followed by consolidation immunotherapy. We investigated the feasibility of chemoimmunotherapy as induction therapy before CRT for LA-NSCLC. We retrospectively analyzed data from 91 patients with unresectable stage III NSCLC treated with either induction chemoimmunotherapy or chemotherapy before CRT. Tumor responses, survival statistics, and toxic effects were compared. The dosimetric parameters of the RT protocol were evaluated. The primary endpoint was progression-free survival (PFS). The overall response (ORR), the depth of response (DpR) were accessed at the end of CRT (ORRinduc+CRT, DpRinduc+CRT) and induction therapy (ORRinduc, DpRinduc). The median PFS (mPFS) were significantly longer in the chemoimmunotherapy induction group (13.5 months vs. 11.2 months; HR, 0.56; 95% CI, 0.32-0.97; p=0.036). The ORRinduc+CRT, median DpRinduc+CRT (mDpRinduc+CRT) and mDpRinduc were significantly higher in the chemoimmunotherapy induction group (ORRinduc+CRT, 84.0% vs. 65.9%, p=0.044; mDpRinduc+CRT, 49.5% vs. 39.0%, p = 0.012; mDpRinduc, 38.5% vs. 28.0%, p=0.044). Incidence of treatment-related adverse events (AE) was similar between groups, with myelosuppression being the most common grade ≥ 3 AE. Regarding radiotherapy, adopting a mapping strategy with a 5-8 mm margin for clinical tumor volume resulted in decreased radiation doses to critical organs in the chemoimmunotherapy induction group. Chemoimmunotherapy induction therapy before CRT improves efficacy with comparable incidence of AEs compared to chemotherapy induction in LA-NSCLC patients. Further studies are warranted to validate these findings.

8789 Unraveling Von Hippel Lindau Syndrome: A Comprehensive Analysis of Clinical Manifestations, Age-Related Variations, and Tumor Prevalence in a Specialized Endocrine Center

Abstract Disclosure: K.K. Pasam: None. Y. Gupta: None. A. Goyal: None. N. Tandon: None. Introduction: This study presents a thorough examination of Von Hippel Lindau (VHL) syndromes, focusing on the clinical spectrum and genetic mutations in our population. Methods: The study, conducted at the Department of Endocrinology and Metabolism from 2016 to 2022. Objectives included studying the spectrum of diseases in index patients and asymptomatic family members. Results: In our study, we identified 19 index cases and 12 asymptomatic cases identified on screening. The analysis of 31 VHL patients revealed a mean age of presentation of 24.2±11.1 years. Pancreatic cysts were the most common manifestation in 61% followed by pheochromocytoma in 54%, cerebellar hemangioblastomas in 45%, retinal angiomas in 39% and renal cell carcinoma in 35%. 16% of patients presented with nonfunctioning pancreatic neuroendocrine tumors, and one case featured an endolymphatic sac tumor.Pheochromocytomas in VHL syndrome presented at a remarkably young age, with an average of 23.1±11.4 years. Bilateral pheochromocytomas were observed in 14 (82%) and hormonal evaluation revealed urinary noradrenaline, normetanephrines, and plasma normetanephrine elevations of 5, 6, and 7-fold, respectively.The median size of pheochromocytomas in VHL syndrome was 5.4 cm. Metastatic pheochromocytoma was observed in one patient. Genetic analysis was available for 9 patients with most common mutation in exon 3 of chromosome 3. Discussion:The average age of VHL syndrome presentation in our cohort is younger than in other Indian studies. Males in our study were 45%, deviating from the absence of gender preponderance associated with VHL. Disparities in age of diagnosis and tumor prevalence compared with other international cohorts highlight potential regional and ethnic variations. Multiple pancreatic cysts in our study, with a prevalence of 61%, lower than the South Indian study's 71%. Literature comparisons indicate pancreatic cyst prevalence ranging from 42% to 51.6%. Cerebellar hemangioblastomas and retinal angiomas, typical VHL lesions, displayed prevalence rates of 45% and 39%, respectively.Pheochromocytoma, the second most common tumor in our cohort (54%), exhibited variations in prevalence compared to international studies. Higher rates reported by Fagundes et al. and Dwivedi et al. from Brazil might be attributed to recruitment biases from endocrine centers.The average age of VHL-associated pheochromocytoma presentation in our study contrasts with MEN2, emphasizing the unique features of VHL. Our study, reporting a 16% prevalence of PNETs, aligns with Binderup et al. The mean age of presentation for VHL-associated PNETs (20.8 ± 3.63 years) contrasts with Western literature, suggesting potential ethnic differences. Conclusion: Our study contributes to a nuanced understanding of VHL syndrome, shedding light on age-related variations, gender distribution, and tumor prevalence. Presentation: 6/2/2024