Treatment Modality For Cancer Research Articles

Bioinspired micro- and nanostructured systems for cancer therapy.

Numerous organisms in nature have demonstrated enhanced biocompatibility, precise tumor targeting capabilities, and efficient tissue traversal within the human body. Drawing inspiration from these organisms, researchers have employed bioengineering, bioconjugation, and micro- or nanotechnology to fabricate bioinspired micro- and nanostructured systems. These systems play a crucial role in addressing the limitations of conventional anticancer drugs and nanomaterials concerning biocompatibility, effective penetration of physiological barriers, as well as selective tumor targeting, thereby leading to improved therapeutic efficacy while minimizing nonspecific adverse effects on healthy cells. Consequently, extensive exploration of these bioinspired micro- and nanostructured systems has been undertaken across various cancer treatment modalities with some progressing into preclinical or clinical stages. However, our understanding of this field remains limited which may impede research progress, clinical translation efforts, and practical applications. Therefore, this study presents a systematic classification of bioinspired micro- and nanostructured systems for cancer therapy that comprehensively elucidates their sources of inspiration and design principles. Furthermore, it extensively discusses the current status of clinical translation efforts while identifying prevailing challenges and exploring future prospects. This work will establish a robust theoretical framework and serve as a valuable reference to facilitate advancements in research and clinical application within this field.

PSMA Radiotheranostics in Prostate Cancer: Principles, Practice, and Future Prospects.

Prostate cancer is a leading cause of cancer-related mortality in men, with metastatic castration-resistant prostate cancer presenting a substantial treatment challenge. The authors focuse on prostate-specific membrane antigen (PSMA) radiotheranostics, particularly lutetium 177 (177Lu)-PSMA radioligand therapy, as an emerging treatment modality for metastatic castration-resistant prostate cancer. The U.S. Food and Drug Administration approval of 177Lu-PSMA-617 marked a substantial advancement in the treatment paradigm of metastatic castration-resistant prostate cancer, based on the VISION trial that showed improved overall survival and quality of life compared with those for standard care. PSMA expression, assessed via PSMA PET, is crucial for patient selection and assessment of treatment eligibility. The authors discuss current practices, including therapy administration, dosing, and side effects, with a particular focus on eligibility criteria and the added value of posttherapy imaging. Response assessment criteria using PSMA PET are discussed, although these require further validation. The discussion of future directions highlights ongoing trials investigating PSMA targeting agents, the extension of radioligand therapy to earlier stages of prostate cancer, and combination therapies. This review underscores the role of PSMA radioligand therapy in the evolving landscape of prostate cancer treatment and its promise for improving patient outcomes. ©RSNA, 2024 Supplemental material is available for this article.

In-field prostate cancer recurrence following radical prostatectomy and salvage radiation.

To define the natural history, patterns of recurrence and treatment modalities for local prostate cancer (PCa) recurrence following radical prostatectomy (RP) and radiation therapy (RT), and to investigate factors that could predict metastasis-free survival (MFS) in this unique patient population. We queried a prospectively maintained PCa registry to identify men developing in-field recurrence (IFR) following RP and RT from 2008 to 2021 at a single institution. IFR was defined as biopsy-proven recurrent PCa or the presence of persistent positron emission tomography-avid lesions in the prior radiation field without evidence of metastasis. Cox regression was conducted to determine predictors of MFS. Kaplan-Meier methods were used to calculate MFS, cancer-specific survival (CSS) and overall survival (OS) for patients in three primary therapy categories: cryoablation, androgen deprivation therapy (ADT) alone, and surveillance. Of 4575 patients from our registry, 108 (2.3%) with IFR were identified. The median (interquartile range [IQR]) time to IFR from salvage treatment was 78 (50-126) months. A total of 29 patients (26%) were managed with cryoablation, 23 (21%) with ADT, and 28 (25%) with surveillance. The median (IQR) follow-up was 76 (48-100) months. There were no statistically significant differences in MFS (P = 0.67) or OS (P = 0.07) among the three primary treatment cohorts. Patients treated with ADT or cryoablation had longer CSS compared to patients managed with surveillance (P = 0.047). We found that IFR may present years after completion of primary treatment for PCa. While curative management strategies may be attempted, local and distant metastatic recurrence is common and often requires systemic therapy.

Impact of the Coronavirus disease pandemic on early breast cancer

ObjectiveTo assess the impact of the COVID-19 pandemic on the presentation, treatment, and survival of patients with early breast cancer (Stage I–III).MethodsThis study utilized data from the Surveillance, Epidemiology, and End Results database from January 1, 2018, to December 31, 2020. Patients diagnosed with primary breast cancer in 2020 were compared to those diagnosed in 2018 or 2019. The primary outcomes were stage distribution and changes in the treatment modalities for early breast cancer. The secondary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS).ResultsWe analyzed 142,038 patients. There has been a decrease in breast cancer diagnoses in 2020, as well as the smaller number of surgeries. The distribution of breast cancer stages among patients exhibited a notable shift in 2020, with a decrease in the proportion of Stage 0-I and an increase in advanced-stage. Additionally, there was a significant decrease in the proportion of breast-conserving surgery (BCS) performed in 2020. The proportion of patients undergoing radiation decreased, while that of chemotherapy cases increased significantly in 2020. Patients showed a shorter treatment delay in 2020 than in 2018 or 2019 (2018: hazard ratio [HR] = 0.969, 95% confidence interval [CI] = 0.956–0.982, p < 0.001; 2019: HR=0.959, 95% CI = 0.946–0.972, p < 0.001). Diagnosis in 2020 showed a significant correlation with worse OS than diagnosis in 2018 (HR = 0.861, 95% CI = 0.743-0.996, p = 0.045).ConclusionWe observed a shift to advanced-stage and a change of treatment modalities of early breast cancer in 2020. The OS of patients with breast cancer was worse during the pandemic than before the pandemic. The findings could provide empirical basis for optimizing cancer prevention and control strategies in future public health emergencies.

Potential predictive biomarkers in antitumor immunotherapy: navigating the future of antitumor treatment and immune checkpoint inhibitor efficacy

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment modality, offering promising outcomes for various malignancies. However, the efficacy of ICIs varies among patients, highlighting the essential need of accurate predictive biomarkers. This review synthesizes the current understanding of biomarkers for ICI therapy, and discusses the clinical utility and limitations of these biomarkers in predicting treatment outcomes. It discusses three US Food and Drug Administration (FDA)-approved biomarkers, programmed cell death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), and microsatellite instability (MSI), and explores other potential biomarkers, including tumor immune microenvironment (TIME)-related signatures, human leukocyte antigen (HLA) diversity, non-invasive biomarkers such as circulating tumor DNA (ctDNA), and combination biomarker strategies. The review also addresses multivariable predictive models integrating multiple features of patients, tumors, and TIME, which could be a promising approach to enhance predictive accuracy. The existing challenges are also pointed out, such as the tumor heterogeneity, the inconstant nature of TIME, nonuniformed thresholds and standardization approaches. The review concludes by emphasizing the importance of biomarker research in realizing the potential of personalized immunotherapy, with the goal of improving patient selection, treatment strategies, and overall outcomes in cancer treatment.

Effects of non-contact electric fields on kidney and liver histology in tumour-induced rats

Background A novel modality of cancer treatment based on exposure to non-contact electric fields has been developed to reduce cancer incidence. However, the safety of the electric field exposure was not fully investigated. Therefore, This study aimed to observe the safety of electric field exposure on kidney and liver structures. Methods Female Sprague-Dawley rats were divided into one control group and three treatment groups. Animals were treated with 7,12-dimethylbenz[a]anthracene for mammary tumour induction and exposed to non-contact electric fields individually for 10 hours a day for three weeks. Fresh samples of the kidney and liver were collected for observation of structural damage in both organs. Both organs were prepared for histopathological cross-sectioning using the paraffin method and Hematoxylin and Eosin staining followed by histological scoring using the post-examination masking method. Results Damages found in the kidney were as follows: thickening of the Bowman capsule, karyolysis, karyorrhexis, pyknosis, cloudy swelling, epithelial sloughing, inflammation, haemorrhage, and congestion. In addition, the number of inflammation and haemorrhage in the kidney structure of healthy rats that were exposed to electric fields was significantly lower than that in the control group. All damages to the kidneys were also found in the liver, but each showed a different degree of damage. Exposure to this electric field can cause haemorrhagic damage to the livers of healthy rats, but not to rats with breast cancer. Conclusions Exposure to non-contact electric fields can cause haemorrhagic damage to the livers of healthy rats, however, in other liver tissues and the kidneys, exposure to this electric field was safe. It can even decrease the number of inflammations and haemorrhages in the kidneys.

Efficacy of radiotherapy for bone metastasis in breast cancer patients treated with cyclin-dependent kinase 4/6 inhibitors

BackgroundIn patients diagnosed withestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, bone metastasesemerge as theprimary siteofsignificant tumor burden. Cyclin-dependent kinase 4/6 (CDK4/6i) inhibitorsare thegold standard in this clinical scenario, while radiotherapy (RT) represents a valuable addition. However, data on the efficacy of this combination remain scarce. We aimed to evaluate efficacy of RT in bone metastatic breast cancer patients treated with CDK4/6 inhibitors. Materials and methods398 patients (pts) with ER-positive HER2-negative breast cancer with bone metastases treated with CDK4/6i between 2018–2024 were analyzed. A total of 114 pts received 177 bone RT concurrently with CDK4/6i or within 6 months before CDK4/6i initiation, including 34 courses of stereotactic-body RT and 143 courses of conventional RT. ResultsThe median progression-free survival (PFS) in pts who received bone RT was 31.0 months, compared to 26.3 months in pts without bone RT. The 2-y PFS for pts with bone RT was 57.1 % [95 % CI: 46.3–66.6 %] vs. 53.2 % [95 % CI: 46.3–59.6 %] for patients without bone RT (p = 0.51). The median overall survival (OS) for pts who received bone RT was 49.1 months, compared to 40.5 months for pts without bone RT. The 3-y OS for pts with bone RT was 63.7 % [95 % CI: 51.5–73.5 %] vs. 55.0 % [95 % CI 46.6–62.6 %] for pts without bone RT (p = 0.50). The 3-y local control for irradiated patients was 86.9 % [95 % CI 72.2–94.1 %]. ConclusionsIn this study, we present the largest cohort published to date of breast cancer patients who received CDK4/6i alongside bone-directed RT. Although the observed differences in survival were not statistically significant, RT remains a viable treatment modality in metastatic breast cancer in some patients.

Two-Year Experience of a Center of Excellence for the Comprehensive Management of Non-Small Cell Lung Cancer at a Fourth-Level Hospital in Bogota, Colombia: Observational Case Series Study and Retrospective Analysis.

Background: This study aimed to provide a comprehensive analysis of 56 patients admitted to the Lung Cancer Clinical Care Center (C3) at Fundación Santa Fe de Bogotá (FSFB) between 2 May 2022 and 22 April 2024. The focus was on demographic characteristics, smoking history, comorbidities, lung cancer types, TNM classification, treatment modalities, and outcomes. Methods: This observational case series study reviewed medical records and included patients over 18 years with a confirmed diagnosis of non-small cell lung cancer (NSCLC). Data were collected and analyzed for demographics, comorbidities, treatment types, biomolecular profiling, and survival rates. Ethical approval was obtained, and data were anonymized. Results: The mean age was 71.8 years with a female predominance (53.6%). A history of smoking was present in 71.4% of patients. Adenocarcinoma was the most common type (75.0%), followed by squamous cell carcinoma (19.6%). At admission, the most frequent TNM stages were IA2 (17.9%) and IVA (16.1%). One-year survival was 68.8%, and 94.3% of stage I-IIIA patients underwent PET scans. Biomolecular profiling revealed 69.2% non-mutated EGFR, 90.4% ALK-negative, and various PDL-1 expression levels. Immunotherapy was received by 91.4% of patients, with Alectinib and Osimertinib being common. Grade III-IV pneumonitis occurred in 5.4% of patients. Conclusions: The study's findings align with existing literature, highlighting significant smoking history, common adenocarcinoma, and substantial use of immunotherapy. Limitations include the observational design, small sample size, and short follow-up period, impacting the generalizability and long-term outcome assessment. Future research should address these limitations and explore longitudinal outcomes and emerging therapies.

Abstract 4144555: Atrial Fibrillation Catheter Ablation among Patients with Mediastinal Radiation; Insight from The National Inpatient Database (2015-2020)

Introduction/Background: Radiation therapy (RT) is one of the most common treatment modalities for mediastinal cancers. RT has multiple adverse cardiovascular effects and it has been identified as an independent risk factor for atrial fibrillation (AF). The efficacy of catheter ablation in AF is well established, however there is limited data on procedural safety and outcomes in patients with mediastinal cancers and history of radiation Methods: The National Inpatient Sample (NIS) was analyzed from 2015-2020 to identify admissions for AF catheter ablation among patients with previous history of mediastinal radiation exposure using the 10-PCS (International Classification of Diseases, procedure coding system) codes. Baseline characteristics were compared between the two groups and multivariate logistic regression was used to analyze hospitalization outcomes. Results: We identified 257,240 admissions for AF catheter ablation of which 1720 patients (0.67%) had a history of mediastinal radiation exposure. In the adjusted analysis, the odds of in-hospital mortality (aOR 0.639, 95% CI 0.34-1.20, p 0.1637), major complications (aOR 0.876, 95% CI 0.73-1.05, p 0.1443), any gastrointestinal or hematological complication (aOR 0.853, 95% CI 0.63-1.15, p 0.3017), renal complications (aOR 1.017, 95% CI 0.88-1.18, p 0.0509) were similar in both cohorts. The odds of any cardiovascular complication (aOR 0.825, 95% CI 0.70-0.97, p 0.0208) was lower and odds of any pulmonary complication (aOR 1.433, 95% CI 1.27-1.62, p<.001) was higher in the mediastinal radiation cohort. Conclusion: AF catheter ablation in patients with history of mediastinal radiation is a safe treatment modality. It is not associated with higher in-hospital mortality or cardiac complications in a nationwide registry.

TMOD-09. NEWLY DESIGNED TUMOR TREATING FIELDS (TTFIELDS) ARRAYS FOR THE MOUSE HEAD DEMONSTRATE EFFICACY FOR TREATMENT OF GLIOBLASTOMA

Abstract Tumor Treating Fields (TTFields) therapy is a cancer treatment modality based on continuous, non-invasive delivery of electric fields. TTFields therapy is approved for treatment of glioblastoma (GBM), delivered to the patient’s brain by two array pairs placed on the scalp. Further research in animals to expand the knowledge regarding TTFields treatment of GBM is limited, as this is mainly performed in mouse models and arrays for application of TTFields to the mouse head are lacking. The small dimensions and specific geometries of the mouse head make the development of such arrays challenging. The aim of this study was to design arrays that will allow efficient and stable delivery of TTFields to the mouse head. To overcome the small head size, we developed a layout with two arrays situated on the head of the mouse, each divided into two smaller disks, and positioned opposite two arrays on the torso. We identified a thin and transparent adhesive tape (facilitating correct array positioning) with good tackiness and easy removal (without leaving residual adhesive on the skin). The arrays met the minimum treatment requirements: current ≥ 50 mA, usage ≥ 75%, field intensity ≥ 1 V/cm RMS. We then conducted an efficacy study with the new arrays, using GL-261 GBM cells intracranially injected into C57BL/6 mice. Treatment with sham-heat (control) or TTFields was initiated 11 days following tumor inoculation and maintained continuously for 12 days. Efficacy was measured via magnetic resonance imaging (MRI) of tumor volume, showing a decrease of 31% at treatment end in TTFields-treated mice versus the control. Overall, the new arrays are flexible, strongly adherent, deliver TTFields at a sufficient intensity, and showed efficacy for treating GBM in mice.

Enhancing Proton Therapy Efficacy Through Nanoparticle-Mediated Radiosensitization.

Proton therapy, characterized by its unique Bragg peak, offers the potential to optimize the destruction of cancer cells while sparing healthy tissues, positioning it as one of the most advanced cancer treatment modalities currently available. However, in comparison to heavy ions, protons exhibit a relatively lower relative biological effectiveness (RBE), which limits the efficacy of proton therapy. The incorporation of nanoparticles for radiosensitization presents a novel approach to enhance the RBE of protons. This review provides a comprehensive discussion of the recent advancements in augmenting the biological effects of proton therapy through the use of nanoparticles. It examines the various types of nanoparticles that have been the focus of extensive research, elucidates their mechanisms of radiation sensitization, and evaluates the factors influencing the efficiency of this sensitization process. Furthermore, this review discusses the latest synergistic therapeutic strategies that integrate nanoparticle-mediated radiosensitization and outlines prospective directions for the future application of nanoparticles in conjunction with proton therapy.

Short- and long-term outcomes of robotic and laparoscopic surgery in rectal cancer: a propensity score-matched analysis.

The relative benefits of robotic surgery and laparoscopic surgery are controversial in rectal cancer. This study compared the short- and long-term outcomes of robotic surgery with those of laparoscopic surgery in patients with rectal cancer using propensity score analysis. This study analyzed consecutive patients who underwent minimally invasive surgery for stage I-III rectal cancer between April 2014 and October 2020. After propensity score matching (PSM), short-term outcomes, relapse-free survival, and overall survival were compared between the robotic surgery (RS) group and the laparoscopic surgery (LS) group. During the study period, 251 patients underwent laparoscopic surgery and 193 underwent robotic surgery. PSM resulted in 160 matched pairs (After PSM, the percentages of patients with stage I, II, and III disease were respectively 56%, 19%, and 24% in the LS group and 49%, 23%, and 28% in the RS group (P = 0.462). Median operation time was 239min in the LS group and 284min in the RS group (P = 0.001). The C-reactive protein level on postoperative day 3 was significantly lower in the RS group (4.63mg/mL vs. 5.86mg/mL, P = 0.013). Postoperative complications, including ileus and Clavien-Dindo grade II or higher complications, were 6% vs. 1% (P = 0.006) and 21% vs. 12% (P = 0.024) in the LS and RS groups, respectively. The 5-year relapse-free survival rate was 88.5% in the LS group and 90.5% in the RS group (P = 0.525); the respective 5-year overall survival rates were 97.3 and 93.8% (P = 0.283). The 5-year cumulative local and distant recurrence rates were 3.3% vs. 3.3% (P = 0.665) and 9.7% vs. 7.7% (P = 0.464) in the LS and RS groups, respectively CONCLUSION: Robotic surgery can be a feasible treatment modality for rectal cancer, with lower frequencies of postoperative ileus and Clavien-Dindo grade II or higher complications than laparoscopic surgery and no difference in long-term outcomes.

Brainstem Toxicity Following Proton Beam Radiation Therapy in Pediatric Brain Tumors: A Systematic Review and Meta-Analysis.

Background: Proton beam radiation therapy (PBRT) is an advanced cancer treatment modality that utilizes the distinctive physical properties of protons to precisely deliver radiation to tumor targets while sparing healthy tissue. This cannot be obtained with photon radiation. In this systematic review and meta-analysis, we aimed to comprehensively assess the risk of brainstem toxicity in pediatric brain tumor patients undergoing PBRT. Methods: With adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a predetermined search strategy was used to identify eligible articles from PubMed, Web of Science, Scopus, and Cochrane Library through July 2024. Results: The current study included a total of 11 eligible articles. The pooled prevalence of patients who suffered from brainstem toxicity was 1.8% (95% CI: 1%, 2.6%). The pooled prevalences of patients with Grade 1 to Grade 5 brainstem toxicity were found to be 10.6% (95% CI: 8.8%, 30%), 1.5% (95% CI: 0.6%, 2.5%), 0.7% (95% CI: 0.3%, 1.1%), 0.4% (95% CI: 0.1%, 0.7%), and 0.4% (95% CI: 0.1%, 0.8%), respectively, with an overall pooled prevalence of 0.7% (95% CI: 0.4%, 1%). Conclusions: This study revealed a relatively low incidence of symptomatic brainstem toxicity and its related mortality in the pediatric population undergoing PBRT. However, further research is encouraged to study the broader effects of PBRT and to explore various factors that may influence the risk of brainstem toxicity in patients treated with PBRT.

New Treatment Modalities for Colorectal Cancer Through Simultaneous Suppression of FSP1 and GPX4.

Ferroptosis is a nonapoptotic type of cell death that is dependent on iron and involves the accumulation of reactive oxygen species. Ferroptosis suppressor protein 1 (FSP1) and glutathione peroxidase 4 (GPX4) are ferroptosis regulators that inhibit ferroptosis through independent pathways. This study assessed the prognostic value of GPX4 and FSP1 expression in colorectal cancer (CRC). We also examined the effects of FSP1 and GPX4 inhibition on cell survival of CRC cells. This study included 206 surgical specimens from Stage II or III CRC patients. FSP1 and GPX4 expression was analyzed immunohistochemically, and the association of their expression levels with clinical outcome was evaluated. We also examined the effects of FSP1 and GPX4 inhibitors on the cell proliferative capacity of CRC cell lines. Overall survival and recurrence-free survival were reduced in patients with high expression of FSP1 or GPX4, and those with both GPX4 and FSP1 expression showed worse prognosis. Positivity of both FSP1 and GPX4 was an independent poor prognostic factor for CRC patients. In CRC cells, the combination of GPX4 and FSP1 inhibitors led to more effective cell death than either inhibitor alone. High expression of both GPX4 and FSP1 is a significant poor prognostic factor for CRC. Simultaneous inhibition of GPX4 and FSP1 to induce ferroptosis may be a novel therapeutic strategy in CRC.

Neoadjuvant chemoradiation for down staging of locally-advanced rectal cancer, and assessment of clinical response with digital rectal examination, magnetic resonance imaging and colonoscopy

Background: In this era of total neoadjuvant treatment (TNT) followed by rectal preservation non-operative management (NOM) or wait and watch (WW) approach for non-metastatic locally-advanced rectal cancer (LARC), reliable and reproducible response evaluation to neoadjuvant therapies forms the cornerstone. Through this study, we try to evaluate clinical response of locally-advanced rectal cancer to neoadjuvant chemoradiation (CRT) in terms of downstaging and total mesorectal excision (TME), and the accuracy of digital rectal examination (DRE), magnetic resonance imaging (MRI) and colonoscopy in the assessment of clinical response to neoadjuvant CRT. Methods: Histologically proven locally advanced rectal adenocarcinoma patients, after pretreatment evaluation, were considered for neoadjuvant chemoradiation, i.e., intensity-modulated radiation therapy (IMRT) with 5-fluorouracil (5-FU) and leucovorin-based concurrent chemotherapy. Patients were evaluated 6-8 weeks after completion of CRT and clinical response assessed by means of DRE, colonoscopy and MRI of pelvis. Following surgery, pathological response was assessed on the final histopathological examination (HPE). Results: Twenty-two patients were accrued for this protocol, of which, 15 (68.2%) were male and 7 (31.8%) were female. Downstaging and TME was achieved in 90.9% of the patients. The sensitivity of DRE, colonoscopy and MRI to detect a complete response was 66.67% and specificity was 94.74%. There were no severe toxicities or deaths reported. Conclusions: Neoadjuvant concurrent chemoradiotherapy with bolus 5-FU and leucovorin is an accepted modality of treatment for locoregionally-advanced rectal cancer, which offers higher rates of downstaging and TME. Digital rectal examination, colonoscopy and MRI together can be reliably used to assess response following neoadjuvant CRT.

Supramolecular Assemblies via Host-Guest Interactions for Tumor Immunotherapy.

Cancer immunotherapy has emerged as one of the most promising modalities for cancer treatment providing hopes of cancer patients with the significant advantages over traditional antitumor therapy methods. Supramolecular assemblies based on host-guest interactions have been widely explored in the field of cancer immunotherapy as the delivery systems. A variety of supramolecular materials show unique features for efficient drug encapsulation, targeting delivery and release, which are favorable to activate antitumor immune responses especially through combination of different treatment strategies. In this review article, we summarize the research progresses of supramolecular assemblies via host-guest interactions for tumor immunotherapy. The construction of various drug delivery systems including hydrogels, liposomes, and polymeric nanoparticles, the drug encapsulation and delivery, as well as advantages and disadvantages are discussed. The perspectives related to future developments in this field are also described.

Evaluation of the robustness of randomized controlled trials for the treatment modalities of esophageal cancer using the fragility index - a systematic review.

Esophageal cancer remains a significant global health challenge. Several treatment modalities were explored in randomized controlled trials (RCTs) in recent decades. This study evaluates the robustness of RCTs focusing on esophageal cancer treatment using the fragility index (FI) and reverse fragility index (RFI). A systematic review of RCTs studying different treatment modalities for esophageal cancer from 2000 to 2023 was conducted. The FI and RFI were utilized to gauge the robustness of statistically significant and non-significant outcomes, respectively. The FI represents the minimal number of patient outcomes that would need to alter to overturn a trial's statistical significance, while RFI indicates the minimal changes required to achieve significance in non-significant results. Out of 4028 studies retrieved, 21 RCTs were included for final analysis. The studies spanned 2001 to 2023 with a mean followup of 66 months (range, 29-108 months) and median number of patients of 194 (range, 45-802). The most common treatment modalities examined in these studies were neoadjuvant chemoradiotherapy (n = 7, 33.3%), neoadjuvant chemotherapy (n = 4, 19.0%), and neoadjuvant immunotherapy (n = 2, 9.5%). Only 5 studies (23.8%) had a statistically significant primary outcome result with a median FI of 6 (IQR, 2.5-8.5). Non-significant primary outcomes were seen in 16 studies (76.2%) with a median RFI of 4 (IQR 1-11) and lost to followup of 0 (IQR 0-4). In the study with the highest FI (10), the FI was lower than the number of patients lost to followup (13). Our findings demonstrate that most RCTs on esophageal cancer treatments did not report significant primary outcomes. The few studies that reported significant results had a low fragility index, suggesting a vulnerability in their findings.

Copper-Consuming Nanoplatform for Alleviating Hypoxia and Overcoming Resistance to Sonodynamic Therapy of Breast Cancer.

Sonodynamic therapy (SDT) is a promising treatment modality for breast cancer; however, its effectiveness is often impeded by the hypoxic tumor microenvironment owing to an insufficient oxygen supply in the solid tumors. To overcome this challenge, we elaborately developed a 4T1 tumor-targeted multifunctional nanoagent by integrating both dendrimer-structured copper chelating agents and organic sonosensitizers (IR820) into a biotin-modified nanoliposome via a microfluidic-assisted self-assembly. In particular, the aforementioned copper chelating agent was constructed by introducing multiple xanthate groups into a dendrimer polymer, which showed a significant selectivity for the consumption of the intracellular copper levels. Based on this, the nanoliposome-based therapeutic not only disrupted the activity of the mitochondrial complex IV to directly inhibit the tumor cell proliferation but also suppressed the resistance to the SDT via inhibition of the oxygen consumption for cellular respiration. Both in vitro and in vivo studies confirmed that the designed nanoagents exhibit a synergistic tumor inhibition effect of copper consumption and IR820-mediated SDT. Taken together, this approach establishes a proof-of-concept for the construction of a copper-ion-modulated nanomedicine to significantly enhance the efficiency of oxygen-dependent cancer treatments.

The dyslipidemic effect of cytostatics in the treatment of early breast cancer as a serious risk factor of cardiovascular diseases.

The development of highly effective anti-cancer therapies over the past several decades has dramatically changed the situation of patients with malignant tumor disease, who currently achieve a high rate of cure in the early stages of the disease. Despite tremendous progress, chemotherapy remains the primary treatment modality for early breast cancer. However, chemotherapy-related complications have a major impact on cardiovascular morbidity and mortality in this group of patients. Almost 80% of women diagnosed with breast cancer are over 50 years of age and already have risk factors for cardiovascular disease, such as age, family history, hypertension, elevated cholesterol, smoking, diabetes, and elevated body mass index. Most breast cancer patients do not die and, in line with the general population, cardiovascular disease remains the most common cause of death. Clinical research, extensive retrospective analyzes and prospective works describe the dyslipidemic effect of cytostatics, which may predispose to the development of atherosclerotic cardiovascular diseases. The administration of neoadjuvant or adjuvant chemotherapy based on anthracyclines and taxanes can lead to an increase in total cholesterol, triacylglycerides, LDL cholesterol and a decrease in HDL cholesterol. Abnormally high concentrations of lipids in the blood represent one of the main risk factors for the development and progression of cardiovascular diseases. The works also indicate a correlation between serum lipid levels and the rate of achieving pathological complete remission after the administration of neoadjuvant chemotherapy. Dyslipidemia is associated with a worse prognosis in breast cancer patients treated with neoadjuvant chemotherapy. The aim of the thesis is to point out the dyslipidemic effects of cytostatics and the risks of atherosclerotic cardiovascular diseases in breast cancer patients who have undergone adjuvant or neoadjuvant chemotherapy for early breast cancer. The identification of cardiovascular risk factors at the beginning of oncological treatment, the monitoring of the lipid spectrum during the treatment and the timely intervention of dyslipidemia treatment escape attention at present.

Boron Agent Delivery Platforms Based on Natural Products for Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) is one of the most promising modalities for cancer treatment due to its minimal invasiveness. Although two types of boron agents are clinically used, several issues persist in their delivery, including poor water solubility, instability in aqueous media, selectivity toward cancer cells, accumulation in cancer cells, retention time in tumor tissue, and efficiency in achieving the boron neutron capture reaction. Addressing these challenges, numerous groups have explored various boron agents to enhance the therapeutic benefits of BNCT. This review summarizes delivery platforms based on natural products for BNCT.