Treatment Of Carcinoma Research Articles

Tumor-intrinsic chemosensitivity assessed by KELIM and prognosis by BRCA status in patients with advanced ovarian carcinomas.

Treatment of high-grade serous ovarian carcinomas relies on surgery and chemotherapy, potentially followed by bevacizumab and/or poly (ADP-ribose) polymerase inhibitors (PARPi). The modeled CA-125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor primary chemosensitivity. Although it is well established that BRCA mutations are associated with platinum sensitivity, the relationship between BRCA status and KELIM score has yet to be elucidated. This study aimed to evaluate the interactions between BRCA and KELIM, and their respective prognostic values. We retrospectively collected data from 743 patients with high-grade serous ovarian carcinomas included in a French nationwide registry (NCT03275298) treated with neoadjuvant platinum-based chemotherapy followed by surgery. We analyzed the interactions between BRCA and KELIM, and their impacts on progression-free survival and overall survival. BRCA-mutated (BRCAm) patients had higher standardized KELIM than BRCA-wild type (BRCAwt) tumors (median 1.16 vs 1.06, respectively; p=0.001). The prognostic value of the KELIM score was independent of BRCA in multivariate analyses. KELIM score and BRCA could be combined to define three prognostic groups: (1) an unfavorable prognostic group with both BRCAwt and unfavorable KELIM (median progression-free survival 12.0 months); (2) an intermediate prognostic group with either BRCAm and unfavorable KELIM, or BRCAwt and favorable KELIM (median progression-free survival of 16.0 and 18.8 months, respectively; HR 0.64 compared with the unfavorable group, p<0.001); and (3) a favorable prognostic group with both BRCAm and favorable KELIM (median progression-free survival 28.8 months; HR 0.37 compared with the unfavorable group, p<0.001). The KELIM score provides complementary prognostic information with respect to BRCA, and discriminates different prognoses within BRCAm or BRCAwt patients. Patients with both BRCAwt/unfavorable KELIM have a poor prognosis, underscoring the urgent need for novel therapeutic strategies.

Prognostic and therapeutic potential of gene profiles related to tertiary lymphoid structures in colorectal cancer.

The role of tertiary lymphoid structures (TLS) in oncology is gaining interest, particularly in colorectal carcinoma, yet a thorough analysis remains elusive. This study pioneered a novel TLS quantification system for prognostic and therapeutic response prediction in colorectal carcinoma, alongside a comprehensive depiction of the TLS landscape. Utilizing single-cell sequencing, we established a TLS score within the Tumor Immune Microenvironment (TIME). Analysis of tertiary lymphoid structure-related genes (TLSRGs) in 1,184 patients with colon adenocarcinoma/rectum adenocarcinoma (COADREAD) from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases led to the identification of two distinct molecular subtypes. Differentially expressed genes (DEGs) further segregated these patients into gene subtypes. A TLS score was formulated using gene set variation analysis (GSVA) and its efficacy in predicting immunotherapy outcomes was validated in two independent cohorts. High-scoring patients exhibited a 'hot' immune phenotype, correlating with enhanced immunotherapy efficacy. Key genes in our model, including C5AR1, APOE, CYR1P1, and SPP1, were implicated in COADREAD cell proliferation, invasion, and PD-L1 expression. These insights offer a novel approach to colorectal carcinoma treatment, emphasizing TLS targeting as a potential anti-tumor strategy.

Deformable dose prediction network based on hybrid 2D and 3D convolution for nasopharyngeal carcinoma radiotherapy.

Radiotherapy is recognized as the primary treatment for nasopharyngeal carcinoma (NPC). Rapid and accurate dose prediction is crucial for enhancing the quality and efficiency of radiotherapy planning. However, the current dose prediction model based on 2D architecture cannot effectively learn the spatial information among slices. Although some studies have explored the incorporation of interslice features through 3D architecture, the resolution properties of medical image anisotropy significantly limit the predictive performance. To address the issues, we propose a novel deformable dose prediction network based on hybrid 2D and 3D convolution for NPC radiotherapy. Specifically, the proposed model innovatively incorporates a 2.5D architecture based on hybrid 2D and 3D convolution, and effectively utilizes the directional information within anisotropic resolutions to achieve cross-scale feature extraction. Additionally, deformable convolution is introduced into the model to enhance the receptive field and effectively handle multi-scale spatial transformations. To improve channel correlation and reduce redundant features, we design a Residual Deformable Squeeze-and-Excitation Module. We conduct extensive experiments on an internal dataset, and the results show that the proposed model outperforms other existing methods in most dosimetric criteria. The proposed model has superior dose prediction performance in NPC radiotherapy, and has important clinical significance for assisting physicists to optimize the treatment plan and improve standardization of radiotherapy planning. The source code is available at https://github.com/CDUTJ102/2.5D-Deformable-UNet .

Upper tract urothelial carcinoma: conservative management - intraluminal adjuvant therapy, and surveillance.

In recent years, intraluminal therapies have become a valid alternative for low grade upper tract urothelial carcinoma (UTUC) patients, as overall survival and cancer-specific survival rates were shown to be comparable to those achieved with radical nephroureterectomy for selected cases. Nonetheless, endoscopic treatment has its limitations. As technology progresses and the demand for endoscopic treatments increases, intraluminal chemotherapy and immunotherapy instillations within the upper tract have increasingly become the subject areas of research. The main intraluminal therapies and relevant instillation approaches are reviewed in this study, including recent publications and their main outcomes. The recurrence rates demonstrated in the literature strengthen the notion that patients with UTUC following current intraluminal treatments have a better prognosis than in the past. Updated relevant guidelines regarding surveillance among this population are also reviewed and summarized. The treatment of upper tract urothelial carcinoma is clinically challenging. Developments in recent years show promising results in this field and ongoing research with new developments is emerging. Further studies are required to better understand the contribution of intraluminal therapies to the management of this disease.

Mixed adenoneuroendocrine carcinomas of the appendix: Is there a survival advantage to right hemicolectomy over appendectomy?

Backgroundthe surgical treatment and prognostic characteristics of mixed adenoneuroendocrine carcinomas (MANEC) of the appendix are not yet available. In this study, we sought to figure out the choice of surgical approach (right hemicolectomy versus appendectomy), and explore the effect of chemotherapy on appendiceal MANEC. Methodspatients with appendiceal MANEC from the Surveillance, Epidemiology, and End Results database (2000–2020) were stratified by gender, race, age group, tumor grade, and TNM stage. Logistic regression and Kaplan-Meier analyses relating TNM stage, grade, and receipt of right hemicolectomy (abbreviated as colectomy) to overall and cancer-specific survival were performed. Results455 patients with appendiceal MANEC were included, of whom 146(32 %) underwent appendectomy and 309(68 %) underwent colectomy. Patients who underwent colectomy had better cancer-specific survival (HR = 0.68, 95%CI (0.47–0.98), P = 0.041) and overall survival (HR = 0.67, 95%CI (0.48–0.93), P = 0.015) than those who underwent appendectomy alone. However, colectomy did not confer any survival advantage over appendectomy in subgroup analyses, including low-grade or high-grade tumors, T1-2N0M0 group, T3-4N0M0 group, node-positive non-metastatic tumors, and metastatic tumors. On multivariate analysis, lack of chemotherapy and high-stage (node-positive or metastatic) were associated with poorer overall survival; high-grade (grade 3–4) and high-stage were primary predictors of cancer-specific mortality. Furthermore, there was no significant association between colectomy and better survival, either overall survival or cancer specific survival, when accounting for tumor stage and grade. ConclusionsOur study found that colectomy did not provide a survival benefit compared to appendectomy alone. Moreover, tumor stage and grade were independent determinants of cancer specific survival; chemotherapy and tumor stage were independent determinants of overall survival.

Molecular Targets and Nano-Technological Approaches in the Treatment of Hepatic Carcinoma.

Liver cancer is a leading cause of cancer-related mortality, with about one million people losing their lives each year. The disease becomes even more dangerous when tumors cannot be removed through surgery. Globally, hepatocellular carcinoma (HCC) ranks third in terms of fatality rates among liver cancers. It is also the most frequent type of liver cancer. Due to the high mortality rate associated with this malignancy, it is a hotspot for researchers looking to improve treatment methods. Nanotechnology plays an important part in these at-tempts. Various types of nanoparticles (NPs) have been investigated for their ability to fight liver cancer. NPs are a vast class of materials. The article details the efforts made to include inorganic NPs, such as silver, gold, metal oxide, platinum, calcium, selenium, and other un-common materials into drug delivery systems (DDS) for therapeutic, carrier, or imaging pur-poses. This review discusses the function of carbon-based NPs in DDS for the treatment of liver cancer, including polymeric, polysaccharide, lipid, and carbon dot NPs, all of which have been extensively researched for this purpose. The purpose of this review is to provide a con-cise overview of recent developments in the field of HCC based on current research and clini-cal diagnosis and treatment guidelines. Further goals include elucidating the current state of nanomaterials research, its limitations, and the potential for future advancements in the field, as well as the use of nanotechnology in the detection and treatment of HCC.

Ferric‐Tannic Nanoparticles Inhibit Early‐Stage Hepatocarcinogenesis by Activating Tumor Immune Responses in Rats

AbstractEarly diagnosis and treatment of hepatocellular carcinoma (HCC) remain major challenges. Significant efforts have been made to find new approaches to address these issues. Ferric‐tannic nanoparticles (FTs) have emerged as promising tools for targeting the early phase of hepatocarcinogenesis due to their preferential accumulation in preneoplastic liver lesions. In this study, the therapeutic potential of FTs is demonstrated in early‐stage hepatocarcinogenesis in rats. FTs inhibit the progression of early hepatocarcinogenesis, reducing hepatic nodules, preneoplastic foci (glutathione S‐transferase placental (GST‐P) form‐positive foci), and HCC cell proliferation. The therapeutic effects of FTs appear to be mediated by inhibiting cell proliferation through the activation of immune responses. FTs show promise as novel immunomodulators or therapeutic agents for the treatment of early‐stage HCC.

Treatment Modalities and Risks of Complication for Patients With Localized Renal Cell Carcinoma Aged 75 and Older.

Partial (PN)/radical (RN) nephrectomy is the standard treatment for localized renal-cell carcinoma (RCC). The potential risks of these procedures are concerns for the elderly. We evaluated perioperative outcomes/survival for patients aged ≥ 75 years with localized RCC who underwent PN, RN, or thermal ablation (TA). Localized RCC patients undergoing PN/RN/TA (2000-2023) were retrospectively reviewed. Logistic-regression assessed factors associated with major complications. Kaplan-Meier estimated survival. A total of 278 patients (≥ 75 years) with RCC who received intervention (107RN, 101PN, and 70TA) were identified. Median age was 78 years. PN patients were younger than other cohorts (77 vs. 79, p = 0.006). Patients with cancer comorbidities underwent TA than PN/RN (93% vs. 88%/76%, respectively). Median tumor size was 4.0, 3.0, and 2.6 cm in RN, PN, and TA cohorts, respectively. RN patients had more complex masses compared to other cohorts (9 vs. 7, p < 0.001). Postoperative complications were significantly greater among PN patients (p = 0.03), but there was no significant difference in Clavien ≥ 3 complications. Peripheral vascular disease (PVD) was associated with Clavien ≥ 3 complications on multivariable analysis (p = 0.03). RN was performed at a stable rate while PN decreased in favor of TA. There was no significant difference in RCC-/non-RCC-specific survival among treatment modalities. It is important to make informed decisions about treating RCC in the elderly to reduce morbidity/mortality. PVD could be a determining factor favoring TA for amenable tumors.

Cardiovascular adverse events and immune-related adverse events associated with PD-1/PD-L1 inhibitors for head and neck squamous cell carcinoma (HNSCC)

While some literature has provided limited information about the potential cardiovascular risk and immune-related adverse events (irAEs) risk associated with PD-1/PD-L1 inhibitors in the treatment of Head and Neck Squamous Cell Carcinoma (HNSCC), the exact relevance is still uncertain. To assess the pharmacovigilance (PV), constituent ratio, severity, and reaction outcomes of major adverse cardiovascular events (MACE) and immune-related adverse events (irAEs) related to PD-1/PD-L1 inhibitors for HNSCC reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed reports of cardiovascular adverse events and irAEs associated with drug therapy for HNSCC submitted to FAERS from the 1st quarter 2015 to the 3rd quarter of 2023. Three PD-1/PD-L1 inhibitors were identified: nivolumab, pembrolizumab and durvalumab. Our primary composite endpoint was the PV of MACE and irAEs related to PD-1/PD-L1 inhibitors in the treatment of HNSCC, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP. 19,372 suspected drug-adverse event reports related to drug treatment in patients with HNSCC were identified, of which 916 reports were cardiovascular events, including 555 reports of MACE and 361 reports of other cardiovascular events. The PV signal regarding MACE was detected in durvalumab (PRR = 2.12, 95% CI: 1.24–3.61; χ2 = 7.71; ROR = 2.19, 95% CI: 1.24–3.86; IC = 1.01; IC025 = 0.07) but not in nivolumab and pembrolizumab. The constituent ratio of MACE in all adverse events caused by nivolumab (OR = 0.38, 95% CI: 0.19–0.73) and pembrolizumab (OR = 0.48, 95% CI: 0.23–0.99) was significantly decreased, compared with durvalumab. A PV signal about other cardiovascular events was detected in durvalumab (PRR = 3.04, 95% CI: 1.73–5.31; χ2 = 16.13; ROR = 3.15, 95% CI: 1.74–5.70; IC = 1.46; IC025 = 0.48), but it was not detected in nivolumab or pembrolizumab. The constituent ratio of other cardiovascular events in all adverse events caused by nivolumab (OR = 0.25, 95% CI: 0.13–0.48) and pembrolizumab (OR = 0.40, 95% CI: 0.20–0.80) was significantly decreased, compared with durvalumab. The constituent ratio of other cardiovascular events in all adverse events caused by nivolumab (OR = 0.61, 95% CI: 0.38–0.99) was significantly decreased, compared with pembrolizumab. There were 40 cases of hypertension. A PV signal about hypertension was detected in pembrolizumab (PRR = 3.72, 95% CI: 1.87–7.43; χ2 = 15.99; ROR = 3.75, 95% CI: 1.87–7.51; IC = 1.53, IC025 = 0.45), but it was not detected in nivolumab. The constituent ratio of hypertension in all adverse events caused by nivolumab (OR = 0.09, 95% CI: 0.09–0.39) was significantly decreased, compared with pembrolizumab. There were 737 cases of irAEs. A PV signal about irAEs was detected in nivolumab (PPR = 1.27, 95% CI: 1.05–1.53; χ2 = 6.38; ROR = 1.28, 95% CI: 1.06–1.56; IC = 0.29, IC025 = −0.00) and pembrolizumab (PPR = 2.20, 95% CI: 1.79–2.71; χ2 = 56.55; ROR = 2.31, 95% CI: 1.84–2.88; IC = 1.03; IC025 = 0.68), but it was not detected in durvalumab. The constituent ratio of irAEs in all adverse events caused by nivolumab (OR = 0.58, 95% CI: 0.44–0.76) significantly decreased, compared with pembrolizumab. By comparing the PV signals, constituent ratio, severity, and reaction outcome of the three drugs, we suppose that nivolumab can be used as the safest PD-1/PD-L1 inhibitor for HNSCC.

Transforming Lung Cancer Care: The Role of Transferosomes in Modern Drug Delivery.

Cancer stands as one of the leading causes of death worldwide, and lung cancer represents its most aggressive and persistent form. Traditional strategies for addressing lung cancer involve various medical therapies such as radiotherapy, chemotherapy, and surgical excision. Despite their prevalence, these conventional methods lack precision and inadvert-ently cause collateral damage to neighboring healthy cells. Recently, nanotechnology has emerged as a potential strategy for the treatment and management of lung carcinomas, bring-ing about a transformative shift in existing approaches. The primary focus of this shift is on minimizing harmful effects and improving the bioavailability of chemotherapy drugs specif-ically targeted at tumour cells. Currently, transferosome nanocarrier systems are widely em-ployed to overcome the obstacles presented by lung cancer. The utilization of transferosome-loaded therapeutic medication administration technology holds tremendous potential in reg-ulating tumour cell growth and treating lung cancer. The purpose of this study is to provide an overview and analysis of current advancements in transferosome-based drug delivery sys-tems, employing inhalational nanoparticle strategies for precise drug targeting in lung cancer management.

The Effect of Statin Usage on Survival in Metastatic Colorectal Cancer Patients Receiving Regorafenib.

Regorafenib is an oral multikinase inhibitor used in later lines for metastatic colorectal carcinoma (mCRC) treatment, but its efficacy and tolerability are low. To improve the response rates and ameliorate adverse effects, different strategies have been implemented. In our study, we examined the effect of statin usage in patients with mCRC treated with regorafenib. This single-center retrospective study included patients with mCRC who were treated with regorafenib between January 2015 and December 2023. The primary outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were adverse effects and the tolerability of regorafenib. The data of 105 patients were collected retrospectively. The median age of the patients was 66 years, and 60 patients were male. Seventeen patients (16.1%) were receiving statins. Statin-using patients were significantly older than non-users (72 years vs. 66.5 years, p=0.05). Comorbid diseases were more common in patients using statins. The median PFS was 1.9 months for statin users and 4.2 months for statin non-users (p<0.001), and the median OS was 4.7 vs. 6.7 months (p=0.01). Cox regression revealed that statin usage was significantly associated with a higher hazard ratio (HR) for PFS (2.53) and OS (2.06) (both p<0.01 and p=0.02, respectively). Statins are associated with decreased survival and response rates in patients with mCRC treated with regorafenib. However, further studies are needed to confirm these results.

Survival benefit added by adjuvant chemotherapy in adenoid cystic carcinoma of salivary gland

The aim of this study was to investigate the potential survival advantages associated with chemoradiotherapy (CRT) compared to radiotherapy (RT) as standalone modalities in the treatment of adenoid cystic carcinoma (ACC) of the salivary glands. Patients diagnosed with resected salivary gland ACC were retrospectively enrolled and categorized into two groups based on the type of adjuvant therapy received. The overall survival outcomes between the CRT and RT cohorts were evaluated using a multivariable Cox model. Post propensity score-matching, a total of 114 patients (57 in each treatment group) were included in the analysis. In the general patient population, CRT did not confer an additional survival benefit compared to RT alone. High-grade tumors, positive surgical margins, and the presence of five or more positive lymph nodes were identified as independent prognostic factors associated with poorer overall survival. Specifically, for patients with positive surgical margins, CRT was significantly associated with improved overall survival relative to RT, displaying a hazard ratio of 0.93 (95% CI: 0.81–0.99). Furthermore, in patients with more than four metastatic lymph nodes, CRT significantly reduced the risk of mortality by 6% (95% CI: 1-24%) when compared to RT alone. Conversely, in patients with high-grade tumors, the addition of adjuvant chemotherapy to RT did not yield significant alterations in survival outcomes compared to RT alone (p = 0.437, HR: 0.95, 95% CI: 0.75–2.07). CRT may offer an overall survival benefit for patients with salivary gland ACC, particularly those characterized by positive margin or the presence of five or more metastatic lymph nodes.

Prognostic Indicators for Precision Treatment of Non-Small Cell Lung Carcinoma.

Non-small cell lung cancer (NSCLC) has established predictive biomarkers that enable decisions on treatment regimens for many patients. However, resistance to therapy is widespread. It is therefore essential to have a panel of molecular biomarkers that may help overcome therapy resistance and prevent adverse effects of treatment. We performed in silico analysis of NSCLC prognostic indicators, separately for adenocarcinomas and squamous carcinomas, by using The Cancer Genome Atlas (TCGA) and non-TCGA data sources in cBioPortal as well as UALCAN. This review describes lung cancer biology, elaborating on the key genetic alterations and specific genes responsible for resistance to conventional treatments. Importantly, we examined the mechanisms associated with resistance to immune checkpoint inhibitors. Our analysis indicated that a robust prognostic biomarker was lacking for NSCLC, especially for squamous cell carcinomas. In this work, our screening uncovered previously unidentified prognostic gene expression indicators, namely, MYO1E, FAM83 homologs, and DKK1 for adenocarcinoma, and FGA and TRIB1 for squamous cell carcinoma. It was further observed that overexpression of these genes was associated with poor prognosis. Additionally, FAM83 homolog and TRIB1 unexpectedly harbored copy number amplifications. In conclusion, this study elucidated novel prognostic indicators for NSCLC that may serve as targets to overcome therapy resistance toward improved patient outcomes.

First-line sunitinib treatment modification in patients with mRCC: nationwide analysis of the Swedish population.

Aim: Assess first-line sunitinib dosing for treatment of metastatic renal cell carcinoma in Swedish clinical practice (2006-2019).Materials & methods: Retrospective analysis of three sunitinib dosing regimens: 2-weeks on, 1-week off (2:1 Start); standard 4-weeks on, 2-weeks off (4:2) and 4:2 start with switch to 2:1 (2:1 Switch).Results: Time-to-treatment discontinuation (95% CI) differed significantly (p<0.001): 6.2 (5.6-7.2), 13.9 (8.1-20.6)and 4.6 (4.3-5.6) months for 2:1 Start (n=320), 2:1 Switch (n=71)and 4:2 (n=704), respectively. Overall survival (95% CI) differed significantly (p<0.001): 21.8 (18.1-26.1), 32.2 (25.1-48.3)and 13.5 (12.3-15.8) months for 2:1 Start (n=320), 2:1 Switch (n=71)and 4:2 (n=704), respectively.Conclusion: Alternative dosing does not compromise clinical efficacy and may provide advantages in terms of improved treatment outcomes. However, due to the changing treatment patterns during this long-term study, and the absence of patient risk category data, caution is required when interpreting the main outcomes.

Ultrasound-guided ablation for T1N0M0 papillary thyroid carcinoma adjacent and non-adjacent danger triangle area: a retrospective comparative study

Objectives To compare the safety and efficacy of ultrasound-guided radiofrequency ablation (RFA) in the treatment of T1N0M0 papillary thyroid carcinoma (PTC) with adjacent and non-adjacent danger triangle area (DTA). Materials and methods This retrospective study involved collecting clinical data of all T1N0M0 PTC patients who underwent RFA between January 2018 and December 2020 at the hospital. A total of 211 patients were enrolled in the study (mean age 43.25 ± 12.30 years, male-to-female ratio = 1:3). Among them, 91 had adjacent DTA involvement, while 120 had non-adjacent DTA involvement. Comparisons were made between the two groups patients regarding tumor volume changes, technical success rates, tumor disappearance, disease progression, complications. Results In both groups, the technical success rate was 100%, with a median follow-up period of 30 months. The rates of complete tumor disappearance were 78% (71/91) and 74.2% (89/120) for the adjacent and non-adjacent DTA(p = .517). Disease progression rates were 2.2% (2/91) and 1.7% (2/120) (p > .99), Complication rates were 3.3%(3/91) in the adjacent DTA group and 1.7% (2/120) in the non-adjacent DTA group (p = .654). At 6th month after ablation, the volume reduction rate (VRR) in the non-adjacent DTA group (42.3%) was higher than in the adjacent DTA group (37.3%) (p = .002). However, no significant differences were observed in VRR between the two groups at 1, 3, 12, 18, 24, 30, and 36 months (p > .05). Conclusion In the treatment of T1N0M0 PTC, the complication rates and short-term efficacy of RFA in adjacent to the DTA did not differ from those of non-adjacent DTA.

Antibody-drug Conjugates in The Management of Advanced Urothelial Carcinoma

For decades, the cornerstone for treatment of advanced urothelial carcinoma (aUC) has consisted of platinum-based chemotherapy regimens, such as GC (gemcitabine plus cisplatin/carboplatin) or MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin). Thereafter, immune checkpoint inhibitors (ICI) were incorporated into the standard of care, initially as monotherapy in subsequent-line settings and more recently as maintenance treatment with chemotherapy in the first-line setting. Recently, the development of antibody-drug conjugates (ADCs) has dramatically shifted the treatment landscape for aUC. ADCs are engineered to function as a biologic “honing missile”, with the aim of delivering its cytotoxic payload to the target cancer cell while remaining stable in circulation and minimizing off-target toxicity. Enfortumab vedotin was the first to demonstrate efficacy in urothelial carcinoma (UC), initially as monotherapy and later in combination with ICI, surpassing the decades-old standard of first-line chemotherapy. The aim of this review is to discuss the evolving field of ADCs in aUC, highlighting the main targets, clinical data, toxicities, and future opportunities. ADCs are engineered to function as a biologic “honing missile”, with the aim of delivering its cytotoxic payload to the target cancer cell while remaining stable in circulation and minimizing off-target toxicity. Enfortumab vedotin was the first to demonstrate efficacy in urothelial carcinoma (UC), initially as monotherapy and later in combination with ICI, surpassing the decades-old standard of first-line chemotherapy. The aim of this review is to discuss the evolving field of ADCs in aUC, highlighting the main targets, clinical data, toxicities, and future opportunities.

Feasibility analysis of using patient-derived tumour organoids for treatment decision guidance in locally advanced head and neck squamous cell carcinoma

BackgroundCurrent treatment for head and neck squamous cell carcinoma (HNSCC) involves surgery, radiotherapy, and chemotherapy. Despite aggressive multimodal approaches, tumour recurrence occurs in 40–60 % of cases, leading to poor survival outcomes. HNSCC lacks common genetic drivers for tailored therapies, and reliable biomarkers for treatment selection are scarce. We investigated the procedural requirements for incorporating drug- and radiosensitivity screens in patient-derived organoids (PDOs) within a clinical trial framework. Patients and methodsFresh tumour samples (N = 198) from 186 HNSCC patients were included. Success rates of organoid establishment were correlated with clinical and procedural parameters. Timelines for establishment of PDO cultures were determined, and their long-term growth potential assessed by serial passaging. Additionally, we conducted whole exome sequencing on matched tumour-organoid pairs. Three PDO models were employed to establish radiosensitivity assays. ResultsIn total, PDO models displaying histomorphological features and genomic alterations of parental tumours were successfully established for 35 % of patient tumours. Success rates rose to 77 % for samples with a tumour cell content of 30 % or higher. Advanced patient age, prior radiotherapy, and delays in tissue processing were identified as negative predictors for engraftment. The estimated time interval needed for screens was compatible with PDO-guided selection of curative-intent radiotherapy regimens. ConclusionsOur findings suggest that with high-quality samples and efficient tissue processing, PDO screens can be successfully performed in 77 % of HNSCC patients. Given the procedural challenges involved, future clinical trials aiming to the utility of PDOs for guiding treatment decisions should consider implementing centralised PDO screening.

Survival improvement over time in renal cell carcinoma treated with nephrectomy: A longitudinal propensity score-matched study.

Surgical treatment for renal cell carcinoma (RCC) has drastically evolved for the past 30 years. However, survival outcomes of RCC according to times have not been fully elucidated, especially in the real-world setting. This study aimed to assess the survival improvement over time in RCC treated with nephrectomy by analyzing a longitudinal cohort using propensity score matching (PSM). We retrospectively reviewed 960 patients with RCC who underwent radical or partial nephrectomy between 1981 and 2018. Patients were divided into two groups according to the time of surgery (1981-1999 vs. 2000-2018). Using PSM, overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were compared between the two groups. Overall, 255 and 705 patients underwent surgery in the earlier (1981-1999) and recent (2000-2018) eras, and PSM derived a matched cohort of 466 patients (233 patients per each group). All patients in the earlier era cohort received open surgeries, whereas about a half (47.4%) of patients in the recent era cohort received minimally-invasive (laparoscopic/robotic) surgeries. After PSM, 137 (29.4%) patients developed recurrence, 105 (22.5%) died of RCC, and 113 (24.2%) died from other causes, with a median follow-up period of 90 months. The recent era cohort had significantly longer OS, CSS, and RFS than the earlier era cohort. Patients with RCC treated in the recent era (2000-2018) showed significantly longer survival than those treated in the earlier era (1981-1999). The improved survival might be attributable to the prevalence of minimally-invasive (laparoscopic/robotic) surgeries.

Carvacrol potentiates immunity and sorafenib anti-cancer efficacy by targeting HIF-1α/STAT3/ FGL1 pathway: in silico and in vivo study.

Hypoxia and tumor cell immunological escape greatly hinder the hepatocellular carcinoma (HCC) treatment efficiency. This study is designed to investigate the capability of carvacrol (CVR) to enhance sorafenib (SOR) anti-cancer efficacy and modulate anti-HCC immunity. CVR target and biological activities were predicted using Swiss Target Prediction website and PASS web server. UALCAN and LinkedOmics databases were used to examine hypoxia-inducible factor 1-alpha (HIF-1α) expression and the relationship between studied genes and tumor clinical features. Kaplan-Meier plotter (KM plotter) and TISIDB databases were used to illustrate correlation of HIF-1α with HCC prognosis and immune infiltration. The binding affinities of CVR to p300, KAT2B, CREBBP, and Hsp90 were demonstrated by molecular docking. In vivo analysis was performed in male Sprague-Dawley rats. The STAT3, JAK2, and fibrinogen-like protein 1 (FGL1) expressions were assessed by qRT-PCR. FGL1 was determined by ELISA. CD8+ T cell number was counted by flow cytometry. HIF-1α was determined by immunohistochemistry. CVR showed an HIF-1α inhibitory potential, which is highly expressed in HCC tissues. Also, elevated HIF-1α expression has been found to be correlated with clinicopathological characteristics, poor survival in HCC patients, and tumor immune cell infiltration. CVR/SOR enhanced liver functions and decreased AFP level. CVR/SOR hindered HCC progression by downregulating STAT3, JAK2, and FGL1. CVR/SOR induced tumor immunity via increasing CD8+ T cells. CVR/SOR is a powerful combination for tumor repression and enhancing SOR efficiency in HCC by modulating FGL1. Moreover, CVR/SOR might exert the aforementioned effects through HIF-1α/STAT3/FGL1 pathway.

The international expert consensus on management of external auditory canal carcinoma.

The objective of this consensus is to provide otolaryngologists with appropriate strategies in the management of external auditory canal (EAC) carcinoma. In the absence of randomized controlled trials, the consensus is based on expert opinions utilizing the Rand/UCLA appropriateness method [Fitch and Aguilar in The RAND/UCLA appropriateness method user's manual, RAND Corporation, Santa Monica, CA, 2001], drawing from existing literature and clinical experience. The management recommendations are structured around 12 key areas, including: definition and pathology, pathogenesis, clinical manifestations, work-up, tumor staging system, surgical management of primary tumor, surgical management of the parotid gland and the temporomandibular joint, lymph node metastasis, radiotherapy, chemotherapy, reconstruction, and follow-up. Management strategies for EAC carcinoma rely on tumor extension and histopathological features. Surgical removal with free surgical margins or combination with radiotherapy, chemotherapy are most often the best options. Given the rarity of the disease, prospective, randomized, multi-institutional clinical trials should be designed to enable reliable comparisons of the outcomes of EAC carcinoma treatments, thereby providing evidence-based clinical data to establish widely accepted guidelines. It emphasizes the need for a multidisciplinary team to be involved in the management of EAC carcinoma, and regular follow-up should be implemented postoperatively.