Treatment Of Carcinoma Research Articles

Red herrings and zebras and TB, oh my! Unexpected bone marrow presentation of Mycobacterium tuberculosis

Abstract Introduction/Objective Epithelioid granulomas are uncommon and non-specific findings in bone marrow samples, and should prompt additional testing for appropriate diagnosis and treatment, especially in the immunocompromised patient. The differential diagnosis for bone marrow granulomas includes infections, neoplasia, autoimmune disease, sarcoidosis, and drug/therapy reaction. Although bone marrow workup to delineate the cause of granulomas should include staining to rule out both infection and lymphoma, morphologic review is often inconclusive. Final diagnosis requires clinical consultation and additional testing. Methods/Case Report A 76-year-old male was admitted to the hospital from the emergency department for a level 2 trauma after being found on the ground ~3 hours after a fall. The patient reported a recent increasing frequency of falls with associated weakness, as well as an almost 30 lb weight loss over the last 3.5 months and low grade fevers over several weeks. His past medical history was significant for treatment for urothelial carcinoma with transurethral resection and BCG therapy, hypertension, coronary artery disease, and peripheral vascular disease. Imaging showed hepatosplenomgaly, suspicious for early cirrhosis, and mild peripancreatic lymphadenopathy. Initial laboratory abnormalities demonstrated mild anemia, low albumin, and mild increase in ALT, AST, and alkaline phosphotase. Initial Infectious Diseases workup was negative for causative etiology (blood cultures, tick-borne parasites, and respiratory pathogens). Patient symptoms did not improve and cytopenias worsened. A bone marrow biopsy showed multiple non-necrotizing epithelioid granulomas. Despite low clinical concern for infectious etiology, mycobacteria blood culture isolated Mycobacterium tuberculosis complex. Final results were available 112 days after specimen collection. Results (if a Case Study enter NA) NA Conclusion Although tuberculosis is commonly associated with granulomatous pathology, infection is very uncommon in North American patients who have not traveled and alternative diagnoses might initially be favored. A high suspicion for mycobacterial infections is essential for diagnosis even in low-incidence populations with no known exposure or risk factor(s).

Advanced Human Papillomavirus–Negative Head and Neck Squamous Cell Carcinoma: Unmet Need and Emerging Therapies

Abstract Despite notable progress in the treatment of advanced head and neck squamous cell carcinoma (HNSCC), survival remains poor in patients with recurrent and/or metastatic (R/M) human papillomavirus (HPV)–negative HNSCC. Worse outcomes in patients who are HPV-negative may be partly related to loss of cell-cycle regulators and tumor suppressors as well as a noninflamed and hypoxic tumor microenvironment, both of which contribute to treatment resistance and disease progression. Anti–programmed cell death protein 1–based regimens as current standard-of-care treatment for R/M HNSCC are associated with durable responses in a limited number of patients. The anti-EGFR mAb, cetuximab, has antitumor activity in this treatment setting, but responses are short-lived and inevitably curtailed due to treatment resistance. Crosstalk between the EGFR and hepatocyte growth factor–dependent mesenchymal–epithelial transition (c-MET) receptor tyrosine kinase pathway is a known mechanism of resistance to cetuximab. Dual targeting of EGFR and c-MET pathways may overcome resistance to cetuximab in patients with HPV-negative HNSCC. Here, we review clinical data of treatments evaluated in patients with R/M HPV-negative HNSCC and highlight the potential role of combining hepatocyte growth factor/c-MET and EGFR pathway inhibitors to overcome cetuximab resistance in this population.

Accelerated radiotherapy in the treatment of anal squamous cell carcinoma – a single institution retrospective evaluation

Accelerated radiotherapy in the treatment of anal squamous cell carcinoma – a single institution retrospective evaluation

Review of Current and Future Medical Treatments in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a complex cancer requiring a multidisciplinary approach. For patients with locally or regionally advanced disease, surgery and/or radiation are the cornerstones of definitive treatment. Medical therapy plays an important adjunct role in this setting, typically consisting of a platinum-based regimen given as induction, concurrent, or adjuvant treatment. While relapsed/metastatic HNSCC has historically been a difficult-to-treat disease with poor outcomes, options have considerably improved with the incorporation of biologics and immune checkpoint inhibitors. Clinical trials are ongoing to investigate novel approaches, including new and combination immunotherapies, targeted therapies, therapeutic vaccines, antibody-drug conjugates, and cellular therapies. The results thus far have been mixed, highlighting the knowledge gaps that continue to challenge the medical oncologist treating HNSCC. Here, we present the most updated and broad review of the current treatment landscape in both locoregional and metastatic HNSCC and discuss the expansive future medical therapies under investigation.

Long-Term Laryngeal Function and Quality of Life Following Treatment of Early Glottic Cancer: A Meta-Analysis.

To review the literature concerning long-term functional outcomes and quality of life (QoL) in patients undergoing transoral laser microsurgery (TLM) versus radiotherapy (RT) for early glottic cancer. A systematic search was conducted across PubMed, Scopus, and Cochrane Library from inception until April 2024. Articles considered were primary studies directly comparing the 2 treatment modalities in a population of T1 and T2 glottic cancer. Interest outcomes were patient report outcome measures (PROMs) of vocal function and QoL, clinician-reported measures, and acoustic analyses parameters. There was no significant difference between TLM and RT in grade, roughness, breathiness, asthenia, strain (relative risk, 1.11; 95% confidence interval [CI], 0.60-2.07; I2 = 90.96; P < .001), Voice Handicap Inventory-30 scores (standardized mean difference [SME] 0.51; 95% CI, -0.04-1.07; I2 = 89.72; P < .001), or fundamental frequency (SME 0.56; 95% CI, -0.14-1.25; I2 = 91.12; P < .001). The TLM group had significantly better performance with regards to jitter (SME 0.54; 95% CI, 0.08-1.00; I2 = 79.42; P < .001) and shimmer (SME 0.53; 95% CI, 0.11-0.95; I2 = 74.94; P < .001). The risk of bias was assessed to be serious. The findings suggest comparable long-term PROMs between TLM and RT in the treatment of early glottic carcinoma, with TLM showing better acoustic analysis outcomes. However, the available evidence remains scarce, of high heterogeneity, and at risk of bias. A direct comparison between TLM and RT through large randomized controlled trials is needed to provide more substantial evidence to determine the optimum treatment.

Histologic Patterns of Ribociclib-induced Liver Injury

Abstract Introduction/Objective Ribociclib, a cyclin dependent kinase (CDK) 4/6 inhibitor, used in the treatment of advanced breast carcinomas, can cause liver injury, often manifesting as elevated liver enzymes. However, the histologic patterns of liver injury caused by Ribociclib have not been well-documented. Our study aims to explore these patterns in patients undergoing Ribociclib treatment. Methods/Case Report Five female patients receiving Ribociclib treatment for breast carcinomas and undergoing liver biopsy post-transaminitis in the past seven years (2017-2024) were identified using our institution’s electronic medical record. Clinical information was collected, and liver biopsies were reviewed for histologic injury patterns. Results (if a Case Study enter NA) The mean age of the patients was 47 years (range 38-68). All patients had liver enzyme abnormalities after starting with Ribociclib: mean time to peak of ALT and AST was 75 days (range 36-125). Mean peak enzyme levels (IU/L) for ALT and AST were 685 and 420, respectively. Liver biopsy showed an acute hepatitis pattern of injury in all five patients: centrizonal confluent necrosis (n=3) and lobular spotty necrosis (n=2). Other findings included: mild cholestasis (n=1), interface hepatitis (n=2), focal bile duct injury (n=2), and mild macrovesicular steatosis without steatohepatitis (n=1). Portal inflammation was mild to moderate, comprising a mixed lymphoplasmacytic infiltrate. One patient had moderate periportal fibrosis without bridging. Ribociclib was withdrawn in all patients; three patients received prednisolone treatment. Three patients were rechallenged with Abemaciclib and two with Palbociclib. All patients had resolution of liver function tests after cessation of Ribociclib therapy. Mean time to normalization of ALT and AST was 46 days (range 30-72) and 62 days (range 30-96), respectively, after holding Ribociclib. Conclusion Ribociclib predominantly causes an acute hepatitis pattern of liver injury and of varying severity. Drug cessation, with or without steroid therapy, and switching to a less hepatotoxic CDK 4/6 inhibitor can be sufficient to restore normal liver function. Screening for liver dysfunction with baseline enzyme tests prior to Ribociclib treatment, as well as serial testing to trend enzyme levels, may help prevent severe liver injury.

Hepatocellular Carcinoma Immunotherapy: Predictors of Response, Issues, and Challenges

Immune checkpoint inhibitors (ICIs), such as durvalumab, tremelimumab, and atezolizumab, have emerged as a significant therapeutic option for the treatment of hepatocellular carcinoma (HCC). In fact, the efficacy of ICIs as single agents or as part of combination therapies has been demonstrated in practice-changing phase III clinical trials. However, ICIs confront several difficulties, including the lack of predictive biomarkers, primary and secondary drug resistance, and treatment-related side effects. Herein, we provide an overview of current issues and future challenges in this setting.

A new potential strategy for cutaneous squamous cell carcinoma treatment by generating serum-based antibodies from tumor-exposed mice.

Current cancer treatment strategies continue to face significant challenges, primarily due to tumor relapse, drug resistance, and low treatment efficiency. These issues arise because certain tumor cells adapt to the host immune microenvironment and evade the immune system. This study presents a new cancer immunotherapy strategy using serum-based antibodies from mice exposed to mouse cutaneous squamous cell carcinoma (mCSCC). The experiment was conducted in three stages. In the first stage, mCSCC cells were isolated and expanded cultured from DMBA/TPA-induced mCSCC. In the second stage, these expanded tumor cells were injected into healthy mice to stimulate the production of anti-tumor antibodies. In the final stage, therapeutic serum was extracted from these healthy mice and reintroduced into the tumor-bearing mice. An ELISA assay was utilized to analyze the levels of p53, Bcl-xL, NF-κB, and Bax. The results showed that the serum treatment not only reduced tumor volume but also reversed changes in p53, Bcl-xL, NF-κB, and Bax. In conclusion, this study developed a new immunotherapeutic strategy for treating mCSCC. However, further research is needed to fully comprehend the mechanism of this serum treatment.

A new potential strategy for cutaneous squamous cell carcinoma treatment by generating serum-based antibodies from tumor-exposed mice

Current cancer treatment strategies continue to face significant challenges, primarily due to tumor relapse, drug resistance, and low treatment efficiency. These issues arise because certain tumor cells adapt to the host immune microenvironment and evade the immune system. This study presents a new cancer immunotherapy strategy using serum-based antibodies from mice exposed to mouse cutaneous squamous cell carcinoma (mCSCC). The experiment was conducted in three stages. In the first stage, mCSCC cells were isolated and expanded cultured from DMBA/TPA-induced mCSCC. In the second stage, these expanded tumor cells were injected into healthy mice to stimulate the production of anti-tumor antibodies. In the final stage, therapeutic serum was extracted from these healthy mice and reintroduced into the tumor-bearing mice. An ELISA assay was utilized to analyze the levels of p53, Bcl-xL, NF-κB, and Bax. The results showed that the serum treatment not only reduced tumor volume but also reversed changes in p53, Bcl-xL, NF-κB, and Bax. In conclusion, this study developed a new immunotherapeutic strategy for treating mCSCC. However, further research is needed to fully comprehend the mechanism of this serum treatment.

Histidine phosphatase-ferroptosis crosstalk modulation for efficient hepatocellular carcinoma treatment

Altering the mechanisms of tumor cell death and overcoming the limitations of traditional chemotherapy is pivotal to contemporary tumor treatment. Inducing ferroptosis, while circumventing safety concerns associated with ferrous vectors, through nonferrous ferroptosis is a promising but underexplored frontier in cancer therapy. Histidine phosphatase (LHPP) has emerged as a novel therapeutic target in treating hepatocellular carcinoma (HCC), but the precise mechanism of LHPP against HCC remains unclear. Herein, we explore the effects of upregulating LHPP expression on ferroptosis and tumor immunogenicity induction by simply delivering a miRNA-363-5p inhibitor (miR-363-5pi) via a previously optimized gemcitabine-oleic acid (GOA) prodrug. Efficient miRNA encapsulation was achieved through hydrogen bonding at an optimized GOA/miRNA molar feed ratio of 250:1, affording spherical nanoparticles with a uniform hydrodynamic size of 147.1 nm and a negative potential of -21.5 mV. The mechanism of this LHPP-ferroptosis crosstalk is disclosed to be an inhibited phosphorylation of the PI3K/Akt pathway, leading to a remarkable tumor inhibition rate of 88.2% in nude mice bearing Bel-7402 tumor xenografts via a combination of LHPP-triggered nonferrous ferroptosis and GOA-induced chemotherapy. The biocompatibility of GOA/miR-363-5pi is strongly supported by their non-hematologic toxicity and insignificant organ damage. In addition, the tumor immunogenic activation potential of GOA/miR-363-5pi was finally explored. Overall, this study is the first work that elucidates the precise mechanism of LHPP for treating HCC via ferroptosis induction and achieves the transformation of chemotherapy and gene therapy into ferroptosis activation with tumor cell immunogenicity, which lays a new therapeutic foundation for the clinical treatment of HCC.Graphical

Alleviation of Tumor Invasion by the Development of Natural Polymerbased Low-risk Chemotherapeutic Systems - review on the Malignant Carcinoma Treatments.

The spread of tumors (48% in men and 51% in women), as well as the protection of malignant tumors by stromal cells and complex blood vessels, pose significant challenges to drug delivery to tumors. Modern chemotherapy, on the other hand, addresses tumor growth suppression by at least 60% through versatile formulation systems and numerous modifications to drug delivery systems. The renewable and naturally occurring polymers present invariably in all living cells form the fundamental foundation for most anticancer drug development. The review aims to discuss in detail the preparations of polysaccharide, lipid, and protein-based drug-loading vehicles for the targeted delivery of prominent anticancer drugs. It also provides an explanation of drug distribution in blood (cumulative releases of nearly 80% drug) and drug accumulation at tumor sites (1-5 mg/kg) due to enhanced permeability and retention (EPR). Specific delivery examples for treating colorectal and breast carcinomas have been presented to distinguish the varied drug administration, bioavailability, and tumor internalization mechanisms between sugar, fatty acid, and amino acid polymers. Current therapy possibilities based on cutting-edge literature are provided, along with drug delivery systems tailored to tumor location and invasive properties. The unique combinations of the three natural polymers provide unparalleled solutions to minimize the toxicity (<20% drug release) of the chemotherapeutic drugs on normal tissues. Moreover, the development of a consolidated drug delivery system has contributed to a substantial reduction (dose reduction from 10.43 μM to 1.9 μM) in the undesirable consequences of higher dosages of chemotherapeutic drugs. The review extensively covers safe chemotherapeutic systems with significant advantages (tumor volume shrinkage of 4T1 cells from 1000 mm3 to 200 mm3) in clinical applications of carcinoma treatments using natural polymers.

Fatal Case of Immune-Related Myocarditis and Myositis Due to Treatment with Immune Checkpoint and Tyrosine Kinase Inhibitors.

Immune checkpoint inhibitor and tyrosine kinase inhibitor combinations have become the new standard of care in the first-line treatment of metastatic clear cell renal cell carcinoma. However, there is a growing concern regarding severe immune-related adverse events. A 78-year-old man with metastatic clear cell renal cell carcinoma, treated with pembrolizumab and axitinib, was admitted to the emergency department 30 days after initiating treatment due to rapidly progressive myositis. Myocarditis with severe ventricular dysfunction was identified. Muscular biopsy findings were compatible with inflammatory myopathy associated with immune checkpoint inhibitors. Initial treatment with high-dose corticosteroids showed an insufficient response. Therapeutic escalation on the third day with methylprednisolone, immunoglobulin, and abatacept resulted in clinical improvement. On the eleventh day, a sudden malignant arrhythmia occurred, followed by cardiac arrest. This represents one of the first case reports describing myocarditis and myositis during treatment with pembrolizumab-axitinib. While immune checkpoint inhibitor may play a major role, it is also possible that the tyrosine kinase inhibitor, while attempting to promote immune modulation, also increases severe toxicities.

Exosomal circPTPRK promotes angiogenesis after radiofrequency ablation in hepatocellular carcinoma.

Radiofrequency ablation (RFA) is an effective treatment for hepatocellular carcinoma (HCC), but the recurrence rate remains high due to angiogenesis in residual cancer cells. We used thermal stimulation to simulate the post-RFA microenvironment. The expression profile of circRNAs between normal control HCC cell-derived exosomes and exosomes after heat stimulation were analyzed by RNA sequencing. Quantitative real-time PCR was applied to evaluate the expression of circPTPRK in exosomes and human umbilical vein endothelial cells (HUVECs). Then, the functions of heat-stimulated HCC cell-derived exosomes and exosomal circPTPRK on HUVECs were unveiled. Transcriptome sequencing was utilized to determine targeted genes of circPTPRK. Heat-stimulated HCC cell-derived exosomes augmented cell proliferation, migration, and angiogenesis of HUVECs. In total, 229 differentially expressed circRNAs were obtained, including 211 upregulated circRNAs and 18 downregulated circRNAs in heat-stimulated HCC cell-derived exosomes. The expression of circPTPRK was remarkably increased in heat-stimulated HCC cell-derived exosomes and the HUVECs incubated with them. Heat-stimulated HCC cell-derived exosomes with circPTPRK knockdown significantly inhibited cell proliferation, migration, and angiogenesis of HUVECs. Mechanistic studies indicated that PLA2G4E is a downstream target of circPTPRK, and PLA2G4E overexpression reversed the inhibitory effect of circPTPRK knockdown on HUVEC angiogenesis. Our results indicated that exosomal circPTPRK activated HUVEC angiogenesis by upregulating PLA2G4E expression.

Exploring the Mechanism of Centipeda minima in Treating Nasopharyngeal Carcinoma Based on Network Pharmacology.

Centipeda minima (CM) is a traditional Chinese herbal medicine used for the treatment of sinusitis and rhinitis, and it possesses anti-cancer properties. However, the mechanism of CM in the treatment of nasopharyngeal carcinoma (NPC) remains unclear. This study aimed to explore the mechanism of CM in the treatment of NPC using a network pharmacology approach. The active components and targets of CM and NPC were screened using TCMSP, SwissTarget, and GeneCards database. The association between CM components and NPC targets or pathways was analyzed using String, Cytoscape 3.9.1, David 6.7, and AutoDock Vina. The Sangerbox platform was used to conduct differential expression and Kaplan-Meier survival analysis of core genes. We identified 17 active compounds of CM and 146 corresponding targeted proteins in NPC. These targets may modulate pathways in cancer, PI3K-Akt, apoptosis, prolactin, relaxin, and TNF signaling. The top 5 core genes of the PPI network were found to be AKT1, STAT3, CASP3, EGFR, and SRC, which may be the main targets of CM in treating NPC. Molecular docking confirmed the binding energies of quercetin with CASP3, 8-Hydroxy-9,10-diisobutyryloxythymol with AKT1, and plenolin with AKT1, which were particularly low, suggesting robust and stable interactions. The expression levels of AKT1, CASP3, EGFR, SRC, MMP9, CCND1, and PTGS2 were significantly higher in head and neck squamous cell carcinoma (HNSC) samples compared to normal samples. In addition, the hub genes could predict the prognosis of HNSC as the Kaplan-Meier survival curve showed that patients with lower expressions of AKT1, STAT3, CASP3, EGFR, MMP9, ESR1, PTGS2, and PPARG had better overall survival. By conducting a network pharmacology approach, we revealed the main ingredients, key targets, and regulatory pathways of Centipeda minima in the treatment of NPC.

Enteritis of the ileal conduit as an adverse event related to immune checkpoint inhibitor use

IntroductionGastroenterocolitis is one of the adverse events related to immune checkpoint inhibitors. However, inflammation of the intestinal lesion used for urinary diversion is not well known as an adverse event related to their use.Case presentationA patient with metastatic bladder cancer was administered pembrolizumab as second‐line treatment. After 12 days of administration, he felt abdominal distention. Computed tomography demonstrated thickening of the ileal conduit wall and bilateral hydronephrosis. Biopsy of the ileal conduit revealed inflammatory granulation tissue. Biopsy of the sigmoid colon also revealed colitis. Therefore, we diagnosed enterocolitis including the ileal conduit related to pembrolizumab. We then started to administer 30 mg prednisolone. After this treatment, we confirmed improvement of the clinical symptoms and healing of the ileal conduit mucosa.ConclusionInflammation of an ileal conduit can occur as an immune‐related adverse event caused by metastatic urothelial carcinoma treatment with pembrolizumab.

High levels of autotaxin and lysophosphatidic acid predict poor outcome in treatment of resectable gastric carcinoma

BackgroundAlthough early-stage gastric cancer is a candidate for curative surgical resection, the absence of specific early symptoms results in a late diagnosis and consequently most patients present advanced or metastatic disease. Identifying noveland tumor-specific biomarkers is needed to increase early detection and match patients to the appropriate treatment. The present study focused on the possible prognostic role of Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (ENPP2)/Autotaxin (ATX) and lysophosphatidic acid (LPA) in Gastro-Esophageal Adenocarcinoma (GEA). High levels of ATX/LPA are associated with several malignancies including gastrointestinal tumors. MethodsUsing a bioinformatics analysis, the incidence of ENPP2 mutations together with its expression in the tumor tissues and the correlation between the presence of mutations and the survival rate were examined in databases of GEA patients. Furthermore, circulating levels of ATX and LPA were studied retrospectively and longitudinally both in patients receiving frontal surgery and in patients receiving preoperative chemotherapy. ResultsOverall findings suggested that although ENPP2 mutations occur at low incidence, their presence was associated with a particular poor Overall Survival (OS). Furthermore, removal of the tumour by surgery resulted in a decrease in serum ATX and LPA levels within five days, regardless of any previous chemotherapy. Basal circulating ATX were associated with the aggressive diffuse GEA and could be considered of negative prognostic value, mainly in combination models with circulating Carcino-Embryonic Antigen (CEA). ConclusionsBased on these observations, clinical trials with ATX-targeted drugs and standard chemotherapy regimens may benefit from selecting GEA patients based on their levels of ATX, LPA and CEA.

Choosing the optimal therapy for metastatic renal cell carcinoma: Insights from a real-world comparative study.

The evolution of combination therapies integrating immune checkpoint inhibitors has revolutionized the first-line treatment of metastatic renal cell carcinoma (mRCC). Although these therapies are clinically approved, direct comparisons between dual immune checkpoint inhibitors (IOIO) and immune checkpoint inhibitors combined with tyrosine kinase inhibitors (IOTKI) in clinical trials are lacking. This gap creates uncertainties in selecting the most appropriate treatment based on patient-specific factors. This study employed the inverse probability of treatment weighting (IPTW) method to analyze progression-free survival (PFS) and overall survival (OS) for patients with mRCC receiving IOIO or IOTKI treatment regimens. A total of 171 patients were analyzed after applying inclusion criteria and propensity scoring. The study found no significant differences in PFS and OS between the two treatment modalities in the IPTW cohort. However, subgroup analyses revealed that IOTKI therapy was associated with better PFS and OS for patients without bone metastases and better OS for patients with a body mass index (BMI) over 25. IOIO therapy showed better OS for patients with a BMI below 18.5. Both IOIO and IOTKI therapies were effective. Therapy selection could be better tailored to patient characteristics by including factors such as the presence of bone metastases and BMI. This study enhances understanding of how patient-specific factors interact with different treatment modalities, potentially guiding more personalized treatment decisions in clinical practice for mRCC.

Integrative multi-omic and machine learning approach for prognostic stratification and therapeutic targeting in lung squamous cell carcinoma.

The proliferation, metastasis, and drug resistance of cancer cells pose significant challenges to the treatment of lung squamous cell carcinoma (LUSC). However, there is a lack of optimal predictive models that can accurately forecast patient prognosis and guide the selection of targeted therapies. The extensive multi-omic data obtained from multi-level molecular biology provides a unique perspective for understanding the underlying biological characteristics of cancer, offering potential prognostic indicators and drug sensitivity biomarkers for LUSC patients. We integrated diverse datasets encompassing gene expression, DNA methylation, genomic mutations, and clinical data from LUSC patients to achieve consensus clustering using a suite of 10 multi-omics integration algorithms. Subsequently, we employed 10 commonly used machine learning algorithms, combining them into 101 unique configurations to design an optimal performing model. We then explored the characteristics of high- and low-risk LUSC patient groups in terms of the tumor microenvironment and response to immunotherapy, ultimately validating the functional roles of the model genes through in vitro experiments. Through the application of 10 clustering algorithms, we identified two prognostically relevant subtypes, with CS1 exhibiting a more favorable prognosis. We then constructed a subtype-specific machine learning model, LUSC multi-omics signature (LMS) based on seven key hub genes. Compared to previously published LUSC biomarkers, our LMS score demonstrated superior predictive performance. Patients with lower LMS scores had higher overall survival rates and better responses to immunotherapy. Notably, the high LMS group was more inclined toward "cold" tumors, characterized by immune suppression and exclusion, but drugs like dasatinib may represent promising therapeutic options for these patients. Notably, we also validated the model gene SERPINB13 through cell experiments, confirming its role as a potential oncogene influencing the progression of LUSC and as a promising therapeutic target. Our research provides new insights into refining the molecular classification of LUSC and further optimizing immunotherapy strategies.

Clinical pathological features and radiotherapy treatment for adenoid cystic carcinoma of the head and neck

Clinical pathological features and radiotherapy treatment for adenoid cystic carcinoma of the head and neck

Impact of immune-related adverse events on survival among patients with head-and-neck squamous cell carcinoma.

Aim: Immune-checkpoint inhibitors (ICIs) have revolutionized treatment of metastatic head and neck squamous cell carcinomas (HNSCCs). Our goal was to assess for an association between immune-related adverse events (irAEs) and clinical outcomes for patients on ICIs.Methods: We analyzed a cohort of 110 HNSCC patients who received ICI therapy at the University of Virginia.Results: On review, 48% of our patients experienced an irAE with the most common events being hypothyroidism (30%), dermatitis (14%) and hepatitis (11%). Women were more likely to experience irAEs. Treatment interruption/discontinuation occurred in 43% patients with irAEs. Development of irAEs was associated with superior objective response rate (68 vs. 39%, p=0.009), with a greater rate of CR (17 vs. 5%) and PR (32vs. 16%). Twelve patients underwent ICI re-treatment following irAE, with 17% attaining a complete disease response, 25% attaining a partial response, 33% achieving stable disease and 25% experiencing disease progression with ICI resumption.Conclusion: Development of irAE was associated with superior objective response rate, with a greater rate of CR and PR. ICI re-treatment following irAE was feasible in a significant proportion of patients and can be attempted in carefully selected patients, given the dearth of second-line therapies for these patients.