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This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Authors. The authors have independently identified an error in the formula that was utilized to calculate the Quality Adjusted Life Years which invalidates the data and the conclusion of the paper. The authors have contacted the journal requesting to retract the article. Apologies are offered to the readers of the journal for any confusion or inconvenience that may have resulted from the publication of this article. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To recognise that assessing the competence of nurses delivering systemic anticancer therapy (SACT) is essential to ensure high-quality patient care • To learn about the development of a digital SACT competency passport that aims to improve learning experience and accessibility for users • To contribute towards revalidation as part of your 35 hours of CPD (UK readers) • To contribute towards your professional development and local registration renewal requirements (non-UK readers). Robust competency assessment of systemic anticancer therapy (SACT) nurses ensures high-quality care is delivered to patients. The UK Oncology Nursing Society (UKONS) developed the SACT competency passport to support training and assessment of SACT nurses. Used throughout the UK and the Republic of Ireland, the passport benefits staff, patients and employers. Limitations in terms of its accessibility and interactivity prompted UKONS to commission the creation of a digital version in the form of an app. This article introduces the app and discusses the features aiding the passport’s use. It also explains how to complete and mark the passport, how to assess others with it and how to provide feedback. Finally, the authors provide information about the implementation of the app and future developments. [ABSTRACT FROM AUTHOR]

Twelve (N^N^N)platinum pyridyl complexes, (N^N^N)Pt(pyF), were synthesised and investigated for their singlet oxygen generation and potential biological activities. They exhibited 1IL and 1MLCT absorption transitions at approximately 325 and 360 nm, identified through TD-DFT calculations. Luminescence was observed only in the L1-derived compounds in solution, with a dual emission with the main contribution of phosphorescence under deaerated conditions. Room temperature phosphorescence was detected in all solid-state cases. Electron-withdrawing substituents at specific positions (R1 and X) and the number of fluorine atoms in R2 were found to enhance the photosensitizing capabilities of these compounds. Biological assessments, including cytotoxicity and photocytotoxicity, were conducted to evaluate their potential as chemotherapeutic agents and photosensitizers. Complexes with chloro substitution in the N^N^N tridentate ligand of the central pyridine ring exhibited promising chemotherapeutic properties. Ancillary pyridine ring substitution became significant under irradiation conditions, with fluoromethylated substituents enhancing cytotoxicity. Complex 2-CF3 was the most efficient singlet oxygen producer and a highly effective photosensitizer. CHF2-substituted complexes also showed improved photosensitizing activity. DNA binding studies indicated moderate interactions with DNA, offering insights into potential biological applications. [ABSTRACT FROM AUTHOR]

Microtubule polymerization inhibitors (MPIs) have long been used as anticancer agents because they inhibit mitosis. Microtubules are thought to play an important role in the migration of tumor cells and the formation of tumor blood vessels, and new MPIs are being developed. Many clinical trials of novel MPIs have been conducted in humans, while some clinical studies in dogs have also been reported. More attempts to apply MPIs not only in humans but also in the veterinary field are expected to be made in the future. Meanwhile, MPIs have a risk of cardiotoxicity. In this paper, we review findings on the pharmacological effects and cardiotoxicity of MPIs, as well as the mechanisms of their cardiotoxicity. Cardiotoxicity of MPIs involves not only the direct effects of MPIs on cardiomyocytes but also their effects on vascular function. For example, hypertension induced by impaired vascular function also contributes to the exacerbation of myocardial damage, and blood pressure control may be useful in reducing cardiotoxicity. By combined administration of MPIs and other anticancer agents, MPI efficacy may be enhanced, thereby potentially allowing to keep MPI dosage low. Measurement of myocardial injury markers in blood and echocardiography may be useful for monitoring cardiotoxicity. In particular, two‐dimensional speckle tracking may have high sensitivity for the early detection of MPI‐induced cardiac dysfunction. The exploration of the potential of new MPIs while understanding their toxicity and how to deal with them will lead to the further development of cancer chemotherapy. Microtubule polymerization inhibitors (MPIs) inhibit tumor cell mitosis, migration, and tumor angiogenesis. Clinical trials in humans and dogs have been conducted. However, MPIs have cardiotoxicity. Monitoring myocardial injury markers and echocardiography, particularly two‐dimensional speckle tracking, is recommended. Non‐clinical studies have reported that blood pressure control or combination with other anticancer drugs reduces cardiotoxicity. The exploration of the potential of new MPIs while understanding their toxicity and how to deal with them will lead to the further development of cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction: The leading causes of mortality and morbidity in developed countries worldwide are malignant and cardiovascular diseases. This paper focuses on cardiovascular complications associated with the therapy of malignant diseases. These adverse effects can develop during or immediately after treatment, as well as several years after the cessation of chemotherapy. Cardiotoxic chemotherapy is a type of cancer treatment that can affect all organs, but the heart is particularly sensitive due to its metabolism. These drugs work by damaging rapidly dividing cancer cells. However, they can also harm healthy cells, leading to side effects such as reduced cardiac function, cardiac arrhythmias, myocardial infarction, and heart failure. There are several ways to reduce the risk of cardiotoxic effects of chemotherapy, including using low doses of cytostatic drugs, using heart-protective medications, and regularly monitoring the heart’s condition.1-4 Case report: An elderly female patient was referred to the Outpatient Clinic following a confirmed diagnosis of breast cancer. She was mobile, afebrile, without neck masses, skin induration, or redness of the areola. She had a history of bilateral adnexectomy and uterine fibroids. After obtaining consent and inserting an IV cannula, the patient began the AC chemotherapy protocol. Throughout the chemotherapy cycle, the patient was closely monitored. A nurse tracked vital signs (blood pressure, respiration) and watched for any undesirable cardiac arrhythmias. The patient received 3 cycles of chemotherapy without any cardiac side effects. One week after hospitalization, the patient visited the Cardiology Department due to chest pain and radiating pain in her left arm and was admitted to the Coronary Care Unit. Based on 12-lead ECG and laboratory findings, it was evident that she had suffered a myocardial infarction. A nurse conducted monitoring, administered prescribed therapy, and on the third day of treatment, the patient was discharged with instructions for further therapy and lifestyle changes. She continued to receive follow-up care through the outpatient oncology clinic. Conclusion: The occurrence of cardiovascular disease during cancer treatment affects the disease outcome, as well as the quality of life after the cessation of chemotherapy. To provide the best care for patients undergoing chemotherapy, regular cardiological monitoring before, during, and after treatment is essential. [ABSTRACT FROM AUTHOR]

In this paper, a series of cyclometalated bismuth(III) complexes bearing C,O -bidentate ligands were synthesized and characterized by techniques such as UV–vis, NMR, HRMS, and single crystal X-ray diffraction. Meanwhile, their cytotoxicities against various human cell lines, including colon cancer cells (HCT-116), breast cancer cells (MDA-MB-231), lung cancer cells (A549), gastric cancer cells (SGC-7901), and normal embryonic kidney cells (HEK-293) were assessed in vitro. Compared with the clinical cisplatin, most of the synthesized complexes possessed significantly higher degrees of anticancer activity and selectivity, giving a selectivity index of up to 71.3. The structure-activity relationship study revealed that the anticancer performance of these bismuth(III) species depends on the factors of coordination environment surrounding the metal center, such as coordination number, coordination bonding strength, lone 6s2 electron pair stereoactivity. The Annexin V-FITC/PI double staining assay results suggested that the coordination environment-dependent cytotoxicity is ascribable to apoptosis. Western blot analysis confirmed the proposal, as evidenced by the down-regulating level of Bcl-2 and the activation of caspase-3. Furthermore, the representative complexes Bi1 , Bi4 , Bi6 , and Bi8 exhibited relatively lower inhibitory efficiency on human ovarian cancer cells (A2780) than on its cisplatin-resistant daughter cells (A2780/cis), thus demonstrating that such compounds are capable of circumventing the cisplatin-induced resistance. This investigation elucidated the excellent anticancer performance of C,O -coordinated bismuth(III) complexes and established the correlation between cytotoxic activity and coordination chemistry, which provides a practical basis for in-depth designing and developing bismuth-based chemotherapeutics. The relationship between coordination environment and anticancer activity of cyclometalated bismuth(III) complexes with C,O -chelating ligands against various human solid tumor cell lines was elucidated. [Display omitted] • Nine C,O -coordinated bismuth(III) complexes were synthesized as anticancer agents. • The cytotoxicity depended on the coordination environment surrounding the metal center. • Most of the synthesized complexes exhibited high tumor cell selectivity. • The coordination number-environment cytotoxicity was ascribable to cell apoptosis. • These bimuth(III) complexes could circumvent the cisplatin-induced resistance. [ABSTRACT FROM AUTHOR]

Introduction: Hepatic visceral crisis (VC), characterized by a rapid total bilirubin increase with disease progression, poses a life-threatening risk in advanced breast cancer (ABC). International consensus guidelines define VC and touch on impending VC (IVC). Limited data exist on systemic treatments for hepatic VC/IVC. This study explores the safety and efficacy of cisplatin monotherapy in patients with Human Epidermal Growth Factor Receptor 2- negative breast cancer (BC) and hepatic IVC/VC. Methods: In this retrospective single-center cohort study data of patients treated with cisplatin monotherapy (60–80 mg/m2, every 3–4 weeks) between 2016 and 2023 at a reference Cancer Centre in Southern Poland were analyzed. Results: 33 female patients (24/33 hormonal-positive) with the mean age 53.84 years were included. Participants progressed on median 2 prior palliative systemic treatment lines. In 10/23 patients hepatic VC and in 23/33 IVC (rapid, symptomatic liver progression; extensive liver involvement; alanine or aspartate aminotransferase > 2 × normal limit; significant increases in lactate dehydrogenase, alkaline phosphatase, or gamma-glutamyl transferase) were identified. Median progression-free survival was 1.87 months and median overall survival 2.67 months. 33% of the patients presented stable disease or partial response. Eight patients experienced adverse events grade ≥ 3: in five the dose of cisplatin was reduced; two stopped the treatment. Conclusion: Due to the hepatotoxicity of BC-active drugs, specific recommendations for systemic treatment are scarce. Our study explored cisplatin's potential use, finding it to be a viable option in patients with performance status 0 or 1 experiencing hepatic IVC/VC, irrespective of liver function parameters and other factors. [ABSTRACT FROM AUTHOR]

Gynecologic cancer is a critical concern in the field of women's health, and traditional treatment methods have demonstrated limited efficacy for certain advanced and recurrent gynecologic cancers. In recent years, antibody–drug conjugate (ADC) therapy, as an emerging targeted approach, has gained increasing attention as a research hotspot. This review aims to elucidate the structure and mechanism of ADC drugs and explore their application and clinical research progress in gynecologic cancers such as ovarian cancer, cervical cancer, and endometrial cancer. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to provide a review of the clinical evidence for use of ramucirumab (RAM) plus folinic acid (leucovorin), fluorouracil (5-FU), and irinotecan (FOLFIRI) or irinotecan as second-line treatment in gastroesophageal adenocarcinoma (GEA). Methods: A systematic and comprehensive search of PubMed was performed to identify phase 2 clinical trials or retrospective studies using RAM plus FOLFIRI or irinotecan in GEA, including abstracts from major congresses, in addition to published manuscripts. An aggregated review and meta-analysis was performed to assess the effectiveness (overall response rate [ORR] as primary outcome) and safety data of RAM plus FOLFIRI or irinotecan. ORR for each study was calculated with 95% confidence interval estimated from normal approximation. To generate the combined ORR with 95% confidence interval, random-effects meta-analysis was conducted to synthesize response data from available studies. Results: Six studies were identified with non-overlapping populations, 3 phase 2 clinical trials and 3 retrospective studies. Across these studies the ORR ranged from 22% to 38%, and pooled ORR was 25.4%. Two of the 3 studies reported better ORR in patients pretreated with taxanes followed by RAM plus FOLFIRI. Treatment with RAM plus FOLFIRI or irinotecan was well tolerated. Neutropenia and diarrhea were the most common adverse events reported across studies. Conclusion: The studies examined in this review suggest that RAM plus FOLFIRI or irinotecan have activity in previously treated GEA irrespective of prior-taxane use. Overall, RAM plus FOLFIRI or irinotecan was well tolerated with no new safety concerns identified beyond established profiles for these regimens. [ABSTRACT FROM AUTHOR]

Targeting the poly (ADP-ribose) polymerase (PARP) protein has shown therapeutic efficacy in cancers with homologous recombination (HR) deficiency due to BRCA mutations. Only small fraction of acute myeloid leukemia (AML) cells carry BRCA mutations, hence the antitumor efficacy of PARP inhibitors (PARPi) against this malignancy is predicted to be limited; however, recent preclinical studies have demonstrated that PARPi monotherapy has modest efficacy in AML, while in combination with cytotoxic chemotherapy it has remarkable synergistic antitumor effects. Immunotherapy has revolutionized therapeutics in cancer treatment, and PARPi creates an ideal microenvironment for combination therapy with immunomodulatory agents by promoting tumor mutation burden. In this review, we summarize the role of PARP proteins in DNA damage response (DDR) pathways, and discuss recent preclinical studies using synthetic lethal modalities to treat AML. We also review the immunomodulatory effects of PARPi in AML preclinical models and propose future directions for therapy in AML, including combined targeting of the DDR and tumor immune microenvironment; such combination regimens will likely benefit patients with AML undergoing PARPi-mediated cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Brain metastasis (BrM) is prevalent among patients with NSCLC, and surgical resection of BrM constitutes a promising treatment strategy for local management and histopathological diagnosis, although it is offered for a select group of patients. Limited information exists concerning the improvement in performance status (PS) following BrM resection or the outcomes stratified by subsequent systemic therapy. Methods: We conducted a retrospective single-center cohort study including NSCLC patients with surgically resected BrM and focused on the improvement in PS and subsequent therapy after BrM resection. Results: 71 patients were included, and the median overall survival was 18.3 months (95% confidence interval [95% CI]: 8.7, not reached). Patients with NSCLC who underwent surgical resection of BrM showed significant improvement in PS (18% and 39% showed ECOG PS of 0–1, before and after BrM resection, respectively [p = 0.006]), and patients with PS improvement were younger than those with PS unimprovement (median, 62 years versus 66 years; p = 0.041). Regarding subsequent systemic therapy after BrM resection, 21 patients (30%) received cytotoxic chemotherapy, 14 patients (20%) received tyrosine kinase inhibitors (TKIs), 3 patients (4%) received immune checkpoint inhibitors (ICIs), and 21 patients (30%) received no subsequent therapy. The survival outcomes of patients stratified by subsequent systemic treatments suggested the tendency that those who received TKI or ICI showed better survival outcomes, although a small number of patients hindered statistical comparisons. Conclusions: We describe the outcomes of patients with NSCLC who underwent surgical resection of BrM, revealing that younger patients were more likely to anticipate improvement in PS, and patients who received TKI or ICI after BrM resection tended to exhibit a more preferable prognosis. [ABSTRACT FROM AUTHOR]

Background: The previous effects of acupuncture-related interventions in improving chemotherapy-induced peripheral neuropathy (CIPN) symptoms and quality of life (QoL) remain unclear in terms of pairwise comparisons. Aims: This systematic review and network meta-analysis aimed to determine the hierarchical effects of acupuncture-related interventions on symptoms, pain, and QoL associated with CIPN in cancer patients undergoing chemotherapy. Methods: Nine electronic databases were searched, including PubMed, Embase, Cochrane Library, EBSCO, Medline Ovid, Airiti Library, China National Knowledge Infrastructure (CNKI), China Journal full-text database (CJFD), and Wanfang. Medical subject heading terms and text words were used to search for eligible randomized controlled trials published from database inception to May 2023. Results: A total of 33 studies involving 2,027 participants were included. Pairwise meta-analysis revealed that acupuncture-related interventions were superior to usual care, medication, or dietary supplements in improving CIPN symptoms, CIPN pain, and QoL. Furthermore, network meta-analysis indicated that acupuncture plus electrical stimulation (acupuncture-E) had the greatest overall effect among the various interventions. The surface under the cumulative ranking curve (SUCRA) revealed that acupuncture-E ranked the highest in improving CINP symptoms. Acupuncture alone was most effective in reducing CIPN pain, and acupuncture plus moxibustion (acupuncture-M) ranked highest in enhancing QoL. Conclusion: This finding suggests that acupuncture-related interventions can provide patients with benefits in improving CIPN symptoms, pain, and QoL. In particular, acupuncture-E could be the most effective approach in which the provided evidence offers diverse options for cancer patients and healthcare professionals. Implication for the profession and/or patient care: These findings provide valuable insights into the potential benefits of acupuncture-related interventions for managing symptoms, pain, and QoL associated with CIPN in patients undergoing chemotherapy. Among the various interventions studied, overall, acupuncture-E had the most significant impact and was effective for a minimum duration of 3 weeks. On the other hand, transcutaneous electrical acupoint/nerve stimulation (TEAS) was identified as a noninvasive and feasible alternative for patients who had concerns about needles or the risk of bleeding. It is recommended that TEAS interventions should be carried out for a longer period, preferably lasting 4 weeks, to achieve optimal outcomes. Trial registration: The study protocol was registered in the International Prospective Register of Systematic Reviews. Registration Number: CRD42022319871. [ABSTRACT FROM AUTHOR]

Dental abnormalities are often detected in childhood and are reported to occur with high prevalence in patients who have undergone cancer treatment or chemotherapy. We performed a literature search of PubMed from 2004 to 2024 using the terms "dental anomaly" and "panoramic examination", and 298 potentially relevant articles were found. Thirty-one articles about dental abnormalities matched the eligibility criteria and were extracted for this review. Although the prevalence of tooth agenesis and microdontia in the general population was reported to be approximately 10% and 3%, respectively, the prevalence in patients who had undergone cancer treatment or chemotherapy was higher in all surveys, suggesting that the treatment is related to the occurrence of dental abnormalities. It is important to continue long-term follow-up with patients not only during treatment but also after the completion of treatment. Dental professionals should provide information about dental abnormalities to patients, their guardians, and medical professionals, which may lead to improvement in the quality of life of patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This study evaluated the ability of Large Language Models (LLMs) to classify subjective toxicities from chemotherapy by comparing them with expert oncologists. Using fictitious cases, it was demonstrated that LLMs can achieve accuracy similar to that of oncologists in general toxicity categories, although they need improvement in specific categories. LLMs show great potential for enhancing patient monitoring and reducing the workload of doctors. Future research should focus on training LLMs specifically for medical tasks and validating these findings with real patients, always ensuring accuracy and ethical data management. Introduction: Large Language Models (LLMs), such as the GPT model family from OpenAI, have demonstrated transformative potential across various fields, especially in medicine. These models can understand and generate contextual text, adapting to new tasks without specific training. This versatility can revolutionize clinical practices by enhancing documentation, patient interaction, and decision-making processes. In oncology, LLMs offer the potential to significantly improve patient care through the continuous monitoring of chemotherapy-induced toxicities, which is a task that is often unmanageable for human resources alone. However, existing research has not sufficiently explored the accuracy of LLMs in identifying and assessing subjective toxicities based on patient descriptions. This study aims to fill this gap by evaluating the ability of LLMs to accurately classify these toxicities, facilitating personalized and continuous patient care. Methods: This comparative pilot study assessed the ability of an LLM to classify subjective toxicities from chemotherapy. Thirteen oncologists evaluated 30 fictitious cases created using expert knowledge and OpenAI's GPT-4. These evaluations, based on the CTCAE v.5 criteria, were compared to those of a contextualized LLM model. Metrics such as mode and mean of responses were used to gauge consensus. The accuracy of the LLM was analyzed in both general and specific toxicity categories, considering types of errors and false alarms. The study's results are intended to justify further research involving real patients. Results: The study revealed significant variability in oncologists' evaluations due to the lack of interaction with fictitious patients. The LLM model achieved an accuracy of 85.7% in general categories and 64.6% in specific categories using mean evaluations with mild errors at 96.4% and severe errors at 3.6%. False alarms occurred in 3% of cases. When comparing the LLM's performance to that of expert oncologists, individual accuracy ranged from 66.7% to 89.2% for general categories and 57.0% to 76.0% for specific categories. The 95% confidence intervals for the median accuracy of oncologists were 81.9% to 86.9% for general categories and 67.6% to 75.6% for specific categories. These benchmarks highlight the LLM's potential to achieve expert-level performance in classifying chemotherapy-induced toxicities. Discussion: The findings demonstrate that LLMs can classify subjective toxicities from chemotherapy with accuracy comparable to expert oncologists. The LLM achieved 85.7% accuracy in general categories and 64.6% in specific categories. While the model's general category performance falls within expert ranges, specific category accuracy requires improvement. The study's limitations include the use of fictitious cases, lack of patient interaction, and reliance on audio transcriptions. Nevertheless, LLMs show significant potential for enhancing patient monitoring and reducing oncologists' workload. Future research should focus on the specific training of LLMs for medical tasks, conducting studies with real patients, implementing interactive evaluations, expanding sample sizes, and ensuring robustness and generalization in diverse clinical settings. Conclusions: This study concludes that LLMs can classify subjective toxicities from chemotherapy with accuracy comparable to expert oncologists. The LLM's performance in general toxicity categories is within the expert range, but there is room for improvement in specific categories. LLMs have the potential to enhance patient monitoring, enable early interventions, and reduce severe complications, improving care quality and efficiency. Future research should involve specific training of LLMs, validation with real patients, and the incorporation of interactive capabilities for real-time patient interactions. Ethical considerations, including data accuracy, transparency, and privacy, are crucial for the safe integration of LLMs into clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Elderly cancer patients represent a population particularly susceptible to nutritional alterations, which can have an impact on overall survival and chemotherapy tolerance. The effects of nutritional interventions in this frail population have not been adequately examined in previous review studies. We conducted a systematic review of the existing literature on the effects of oral nutritional supplements (ONSs) and dietary counseling during chemotherapy in older oncology patients. Various types of ONS were investigated, including multimodal intervention with tailored nutritional counseling, whey protein supplements, amino acids supplements (including immune nutrition supplements), and fish oil omega-3-enriched supplements. ONSs showed promise in reducing chemotherapy side-effects and improving nutritional status in older cancer patients, but further studies are needed to explore their efficacy on chemotherapy adherence and overall survival. Further studies are needed to investigate the effects of ONS considering chronological age and frailty criteria, different dietary habits, and specific nutritional assessment like Bioelectrical Impedance Analysis. This study aims to review existing literature on the effect of oral nutritional supplements (ONSs) during chemotherapy in older cancer patients. Electronic databases were searched for relevant studies up to March 2024. The risk of bias in the included studies was evaluated using the Cochrane tool. Eligible studies included randomized, prospective, and retrospective studies evaluating the effect of ONSs in elderly (median age > 65 years) cancer patients during chemotherapy. Data regarding chemotherapy adherence, toxicity, overall survival, and nutritional status were extracted. A total of ten studies, involving 1123 patients, were included. A meta-analysis of the results was not conducted due to the scarcity and heterogeneity of results. Some ONSs were associated with reduced incidence of chemotherapy side-effects, particularly oral mucositis, and improved nutritional status. There was limited or no evidence regarding the impact of ONSs on chemotherapy adherence or overall survival. Various types of ONS were investigated, including multimodal intervention with tailored nutritional counseling, whey protein supplements, amino acids supplements (including immune nutrition supplements), and fish oil omega-3-enriched supplements. ONSs showed promise in reducing chemotherapy side-effects and improving nutritional status in older cancer patients, but further studies are needed to explore their efficacy on chemotherapy adherence and overall survival. Future research should consider both chronological age and frailty criteria, account for dietary habits, and use specific nutritional assessment like Bioelectrical Impedance Analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: This research investigates the effectiveness and safety of totally implantable vascular access devices (TIVADs) used for delivering treatments such as chemotherapy. Over a five-year period, 70 patients received TIVADs through a standardized surgical method under local anesthesia. The study found very low complication rates, with only two notable incidents: one device needed adjustment due to a flipped catheter, and one infection occurred after over three years of use. The procedural success rate was 100%, with devices typically lasting around 22 months, and some even up to five years. These findings suggest that TIVADs are a reliable and safe option for long-term venous access, significantly benefiting routine clinical practices. Background: Daily clinical practice requires repeated and prolonged venous access for delivering chemotherapy, antibiotics, antivirals, parenteral nutrition, or blood transfusions. This study aimed to investigate the performance and the safety of totally implantable vascular access devices (TIVADs) over a 5-year follow-up period through a standardized well-trained surgical technique and patient management under local anesthesia. Methods: In a retrospective, observational, and monocentric study, 70 patients receiving POLYSITE® TIVADs for chemotherapy were included. The safety endpoints focused on the rate of perioperative, short-term, and long-term complications. The performance endpoints included vein identification for device insertion and procedural success rate. Results: The study demonstrated no perioperative or short-term complications related to the TIVADs. One (1.4%) complication related to device manipulation was identified as catheter flipping, which led to catheter adjustment 56 days post-placement. Moreover, one (1.4%) infection due to usage conditions was observed, leading to TIVAD removal 3 years and 4 months post-surgery. Catheter placement occurred in cephalic veins (71.4%), subclavian veins (20%), and internal jugular veins (8.6%). The procedural success rate was 100%. Overall, the implantable ports typically remained in place for an average of 22.4 months. Conclusions: This study confirmed the TIVADs' performance and safety, underscored by low complication rates compared to published data, thereby emphasizing its potential and compelling significance for enhancing routine clinical practice using a standardized well-trained surgical technique and patient management. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small-cell lung cancer is characterized by high morbidity and mortality. Currently, the precision medicine approach in the adenocarcinoma subtype of non-small-cell lung cancer aims to identify genomic alterations that can be targeted in individual patients and offer them appropriate treatment. Several biomarker-guided therapies have been approved, targeting genes frequently altered in adenocarcinoma, such as EGFR, BRAF, MET, ALK, ROS1, RET and NTRK. To overcome the emergence of resistance and increase the efficacy of these targeted therapies, the combination of chemotherapy and targeted therapy has been studied and validated in adenocarcinoma patients with EGFR mutations. This study proposes to examine whether this type of combined approach, which is difficult to study in clinical trials, could be more widely used by targeting other genetic alterations in the MAPK/PI3K pathways or against alterations in the CDNK2A gene in adenocarcinomas but also in squamous-cell carcinomas. The combination of chemotherapy and targeted therapy has been validated in non-small-cell lung cancer (NSCLC) patients with EGFR mutations. We therefore investigated whether this type of combined approach could be more widely used by targeting other genetic alterations present in NSCLC. PDXs were generated from patients with NSCLC adenocarcinomas (ADCs) and squamous-cell carcinomas (SCCs). Targeted NGS analyses identified various molecular abnormalities in the MAPK and PI3K pathways and in the cell cycle process in our PDX panel. The antitumor efficacy of targeted therapies alone or in combination with chemotherapy was then tested in vivo. We observed that trametinib, BKM120, AZD2014 and palbociclib increased the efficacy of each chemotherapy in SCC PDXs, in contrast to a non-insignificant or slight improvement in ADCs. Furthermore, we observed high efficacy of trametinib in KRAS-, HRAS- and NRAS-mutated tumors (ADCs and SCCs), suggesting that the MEK inhibitor may be useful in a wider population of NSCLC patients, not just those with KRAS-mutated ADCs. Our results suggest that the detection of pathogenic variants by NGS should be performed in all NSCLCs, and particularly in SCCs, to offer patients a more effective combination of chemotherapy and targeted therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite recent advances in treatment options, such as chemotherapy, cancer continues to be the second-leading cause of death worldwide. Significant hurdles in the success of chemotherapy regimens include severe adverse effects, as well as drug resistance. As such, there is a strong requirement for novel pharmacological interventions in the treatment of cancer. Natural products, such as monosaccharides, are a promising potential treatment option for cancer due to their low toxicity, high solubility, and high specificity for tumour cells. Several naturally occurring and synthetically modified sugars have displayed toxicity in a variety of cancer and tumour cells. A major hallmark of cancer is the reprogramming of cellular metabolism from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon known as the Warburg effect. To sustain high rates of glycolysis, cancer cells overexpress GLUT transporters and glycolytic enzymes, allowing for the enhanced uptake and consumption of glucose. The Warburg effect may be exploited in the treatment of cancer; certain epimers and derivatives of glucose can enter cancer cells and inhibit glycolytic enzymes, stunting metabolism and causing cell death. These include common dietary monosaccharides (ᴅ-mannose, ᴅ-galactose, ᴅ-glucosamine, ʟ-fucose), as well as some rare monosaccharides (xylitol, ᴅ-allose, ʟ-sorbose, ʟ-rhamnose). This article reviews the literature on these sugars in in vitro and in vivo models of cancer, discussing their mechanisms of cytotoxicity. In addition to this, the anticancer potential of some synthetically modified monosaccharides, such as 2-deoxy-ᴅ-glucose and its acetylated and halogenated derivatives, is reviewed. Further, this article reviews how certain monosaccharides can be used in combination with anticancer drugs to potentiate conventional chemotherapies and to help overcome chemoresistance. Finally, the limitations of administering two separate agents, a sugar and a chemotherapeutic drug, are discussed. The potential of the glycoconjugation of classical or repurposed chemotherapy drugs as a solution to these limitations is reviewed. [ABSTRACT FROM AUTHOR]

To examine the potential correlation between chemotherapy and the risk of individual of second primary endometrial cancer (SEC) in patients with rectal cancer (RC) and assess survival outcomes. The study employed the Surveillance, Epidemiology, and End Results database (SEER) as the primary data source, it encompasses a substantial cohort of patients diagnosed with RC between 1975 and 2018. This study involved a total of 30,847 individuals diagnosed with RC, of whom 168 individuals (5.45‰) experienced SEC. Among them, 107 patients (3.47‰) received chemotherapy treatment, while 61 patients (1.98‰) did not receive chemotherapy. The analysis of the overall occurrence of SEC revealed a significant association between SEC and chemotherapy treatment. Univariate and multivariate analyses confirmed a significant association between chemotherapy treatment and an increased risk of developing SEC in RC patients. Upon implementation of a dynamic analysis on the variables of relative risk and standardized incidence ratios, the results revealed that the likelihood of SEC escalated in tandem with advancing age. The examination of patients who developed SEC after receiving and not receiving chemotherapy revealed no substantial disparities in the 10-year overall survival (OS) and (cancer-specific survival) CSS rates. The results were the same after propensity score matching. Nevertheless, a notable discrepancy emerged when comparing the OS and CSS rates at 10 years between patients afflicted with SEC subsequent to chemotherapy and those afflicted with primary endometrial cancer, and the result was the same situation in the no-chemotherapy group. The use of chemotherapy in RC patients has been associated with an increased probability of developing specific SEC. Therefore, it is imperative to prioritize efforts aimed at reducing chemotherapy-related SEC occurrences and improving the prognosis of affected individuals. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer (EOC) is an often‐fatal malignancy marked by the development of resistance to platinum‐based chemotherapy. Thus, accurate prediction of platinum drug efficacy is crucial for strategically selecting postoperative interventions to mitigate the risks associated with suboptimal therapeutic outcomes and adverse effects. Tissue‐derived extracellular vesicles (tsEVs), in contrast to their plasma counterparts, have emerged as a powerful tool for examining distinctive attributes of EOC tissues. In this study, 4D data‐independent acquisition (DIA) proteomic sequencing was performed on tsEVs obtained from 58 platinum‐sensitive and 30 platinum‐resistant patients with EOC. The analysis revealed a notable enrichment of differentially expressed proteins that were predominantly associated with immune‐related pathways. Moreover, pivotal immune‐related proteins (IRPs) were identified by LASSO regression. These factors, combined with clinical parameters selected through univariate logistic regression, were used for the construction of a model employing multivariate logistic regression. This model integrated three tsEV IRPs, CCR1, IGHV_35 and CD72, with one clinical parameter, the presence of postoperative residual lesions. Thus, this model could predict the efficacy of initial platinum‐based chemotherapy in patients with EOC post‐surgery, providing prognostic insights even before the initiation of chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is the most common and aggressive brain tumor in adults. Despite surgery, radiation, and chemotherapy, survival rates remain low, which emphasizes the urgent need for improved therapies. Current preclinical models use untreated tumors, which do not reflect the clinical scenario where patients already receive initial treatments. This review examines the effects of current treatments on the properties of recurrent tumors and evaluates preclinical models that incorporate these standard treatments to better mimic real patient conditions. Improving these models could help to identify more effective treatments, potentially leading to better outcomes for glioblastoma patients. Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated a benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. In this review, we discuss the impact of treatment—surgery, radiation, and chemotherapy—on GBM. We also provide a summary of treatments used in preclinical models, advocating for their integration to enhance the translation of novel strategies to improve therapeutic outcomes in GBM. [ABSTRACT FROM AUTHOR]

Background and Objective: Olanzapine (OLZ) containing regimens are approved in adults for chemotherapy-induced nausea and vomiting (CINV) receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC), and the same has not been approved in the pediatric population. In order to generate data regarding the efficacy and safety of OLZ as an adjunct to the standard of care (SoC) for CINV in pediatric patients receiving HEC/MEC, the review authors performed this systematic review and meta-analysis. Methods: A systematic literature search was performed through the databases Cochrane Library, Pub Med, and clinicaltrials.gov, from inception to September 2023, using keywords: "chemotherapy" and "olanzapine," "nausea" and "vomiting." Randomized clinical trials published in English that analyzed the efficacy and safety of olanzapine as an adjunct to SoC were included. The essential outcomes included in this study were the proportion of patients with no emesis in the acute and delayed phase, patients with no nausea in the acute and delayed phase, the proportion of patients requiring rescue medication, and the proportion of patients with reduced CNS arousal. Results: In the OLZ group, a greater number of patients had no emesis both in the acute and delayed phase (RR = 1.22; 95% CI = 1.09-1.37; P =.0004); and (RR = 1.23; 95% CI = 0.92-1.63; P =.16) respectively. Similarly, a higher number of patients showed no nausea both in the acute and delayed phase (RR = 1.08; 95% CI = 0.78-1.48; P =.66) and (RR = 1.12; 95% CI = 0.79-1.61; P =.52) respectively. The use of rescue medication was significantly less in the OLZ group (RR = 0.62; 95% CI = 0.42-0.91; P =.01). More patients experienced reduced CNS arousal in the OLZ group (RR = 2.97; 95% CI = 2.02-4.38; P <.0001). Conclusions: Olanzapine as an adjunct to the SoC may be effective in acute emesis, which may also reduce the use of rescue medication. Reduced CNS alertness was the significant adverse effect observed. For other endpoints, more studies are required to substantiate its role in CINV. [ABSTRACT FROM AUTHOR]

The addition of intravenous (i.v.) chemotherapy to i.v. immunotherapy for patients with lung cancer results in improved overall survival but is limited by synergistic side effects and an unknown, highly variable final cytotoxic dose within the tumor. The synergy between i.v. chemo- and immunotherapies is hypothesized to occur as a result of cell injury caused by chemotherapy, a mechanism demonstrated to drive antigen presentation within the tumor microenvironment. Intratumoral delivery of chemotherapy may thus be optimized to maximize tumor cell injury. To assess the balance between the damage versus the death of tumor cells, we developed a computational model of intratumoral dynamics within a lung cancer tumor for three different chemotherapy agents following direct injection as a function of location and number of injection sites. We based the model on the morphology of a lung tumor obtained from a thoracic CT scan. We found no meaningful difference in the extent of tumor cell damage between a centrally injected versus peripherally injected agent, but there were significant differences between a single injection versus when the total dose was apportioned between multiple injection sites. Importantly, we also found that the standard chemotherapeutic concentrations used for intravenous administration were effective at causing cell death but were too high to generate significant cell injury. This suggests that to induce maximal tumor cell injury, the optimal concentration should be several orders of magnitude lower than those typically used for intravenous therapy. [ABSTRACT FROM AUTHOR]

Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better efficacy profile without compromising efficacy. [ABSTRACT FROM AUTHOR]

The pharmacological treatment of cancer has evolved from cytotoxic to molecular targeted therapy. The median survival gains of 124 drugs approved by the FDA from 2003 to 2021 is 2.8 months. Targeted therapy is based on the somatic mutation theory, which has some paradoxes and limitations. While efforts of targeted therapy must continue, we must study newer approaches that could advance therapy and affordability for patients. This work briefly overviews how cancer therapy has evolved from cytotoxic chemotherapy to current molecular-targeted therapy. The limitations of the one-target, one-drug approach considering cancer as a robust system and the basis for multitargeting approach with polypharmacotherapy using repurposing drugs. Multitargeted polypharmacotherapy for cancer with repurposed drugs should be systematically investigated in preclinical and clinical studies. Remarkably, most of these proposed drugs already have a long history in the clinical setting, and their safety is known. In principle, the risk of their simultaneous administration should not be greater than that of a first-in-human phase I study as long as the protocol is developed with strict vigilance to detect early possible side effects from their potential interactions. Research on cancer therapy should go beyond the prevailing paradigm targeted therapy. [ABSTRACT FROM AUTHOR]

Primary bone lymphoma of the spine (PBL) is a rare entity that may be misdiagnosed due to its atypical location and clinical and imaging features mimicking certain pathologies as infectious processes, which complicates and delays diagnosis. Our case reports a patient in her sixties who had been suffering from chronic low back pain for a year, and had gradually started to develop cruralgia. She underwent a blood sample, magnetic resonance imaging (MRI), and positron emission tomography (18F-FDG-PET/CT) which revealed inflammatory syndrome, and an image of spondylodiscitis of the lumbar spine associated with a morphological and metabolical widespread invasion posteriorly suggesting epiduritis. No other lesions were found on the rest of the body. Neurosurgical management was performed and a biopsy was made. Histological results showed aggressive and diffuse large B-cell lymphoma, suggesting a diagnosis of PBL. This case highlights the first case of spondylodiscitis mimicking PBL in the lumbar spine, the intricacies of the diagnostic work-up, and the complexity of discriminating with an infectious process in the spine, as both have a similar, non-specific clinical presentation, while morphological and metabolic findings can be alike. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the clinical efficacy and safety of anlotinib as maintenance therapy in patients with advanced cholangiocarcinoma following first-line chemotherapy. Methods: This retrospective study enrolled 154 patients with advanced biliary tract cancer admitted to the hospital between January 2020 and December 2022. All patients received first-line intravenous chemotherapy with gemcitabine combined with cisplatin, oxaliplatin, or tegafur. Among the 106 patients who achieved disease control, 47 received oral anlotinib hydrochloride (12 mg daily, 2 weeks on/1 week off) as maintenance therapy. Clinical efficacy, including ORR, DCR, DOR, PFS, and OS, was compared between the anlotinib maintenance and non-maintenance groups. Subgroup analysis based on NLR levels was also performed. Results: Among the 47 anlotinib maintenance patients, the ORR was 21.28% and the DCR was 51.06%. The median DOR was 36 weeks, and the median PFS was 43 weeks in the anlotinib group, versus 28 weeks and 38 weeks in the non-maintenance group, respectively. The median OS was not reached in the anlotinib group but was 48 weeks in the non-maintenance group. Patients receiving anlotinib maintenance had significantly longer DOR, PFS, and OS (all p < 0.05). Patients with low NLR levels had better survival benefits from anlotinib. Conclusion: Maintenance therapy with anlotinib demonstrates potential efficacy and a reliable safety profile in patients with advanced cholangiocarcinoma following first-line treatment. The efficacy of anlotinib therapy appears to be influenced by NLR levels. Further validation with larger sample sizes is warranted to strengthen the robustness and reliability of the results. [ABSTRACT FROM AUTHOR]

Objective: To determine the cost-effectiveness of imported immune checkpoint inhibitors (ICIs) such as atezolizumab and durvalumab, and domestic ICIs like serplulimab and adebrelimab, in combination with chemotherapy for extensivestage small cell lung cancer (ES-SCLC) in China. Methods: Using a 21-day cycle length and a 20-year time horizon, a Markov model was established to compare the clinical and economic outcomes of five first-line ICIs plus chemotherapy versus chemotherapy alone, as well as against each other, from the perspective of the Chinese healthcare system. Transition probabilities were estimated by combining the results of the CAPSTONE-1 trial and a published network meta-analysis. Cost and health state utilities were collected from multiple sources. Both cost and effectiveness outcomes were discounted at a rate of 5% annually. The primary model output was incremental cost-effectiveness ratios (ICERs). A series of sensitivity analyses were preformed to assess the robustness of the model. Results: In the base-case analysis, the addition of first-line ICIs to chemotherapy resulted in the ICERs ranged from $80,425.31/QALY to $812,415.46/QALY, which exceeded the willing-to-pay threshold set for the model. When comparing these first-line immunochemotherapy strategies, serplulimab plus chemotherapy had the highest QALYs of 1.51286 and the second lowest costs of $60,519.52, making it is the most cost-effective strategy. Our subgroup-level analysis yielded results that are consistent with the base-case analysis. The sensitivity analysis results confirmed the validity and reliability of the model. Conclusion: In China, the combination of fist-line ICIs plus chemotherapy were not considered cost-effective when compared to chemotherapy alone. However, when these fist-line immunochemotherapy strategies were compared with each other, first-line serplulimab plus chemotherapy consistently demonstrated superiority in terms of cost-effectiveness. Reducing the cost of serplulimab per 4.5 mg/kg would be a realistic step towards making first-line serplulimab plus chemotherapy more accessible and cost-effective. [ABSTRACT FROM AUTHOR]

Simple Summary: Secondary cytoreductive surgery is a treatment option for patients with relapsed platinum-sensitive epithelial ovarian cancer, yet the precise indications and criteria for patient selection remain to be outlined. Furthermore, the impact on progression-free and overall survival remains unclear. The objective of this systematic review was to determine the precise indications for secondary cytoreductive surgery and to elucidate the factors contributing to favorable outcomes associated with the intervention compared to conventional treatment modalities like standard-of-care chemotherapy. Our review confirmed that secondary cytoreductive surgery maintains morbidity, mortality, and quality of life standards for patients. While the trials included utilized different selection criteria for the procedure, our findings underscore the importance of careful patient selection to improve survival in conjunction with conventional chemotherapy. Secondary cytoreductive surgery is a treatment option for relapsed platinum-sensitive epithelial ovarian cancer, but no clear indications are defined for the procedure. This systematic review aims to establish clear indications and compare outcomes versus standard-of-care chemotherapy. We conducted an electronic literature search across three databases and identified 2033 articles, including three phase 3 randomized controlled trials (RCT). The review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (no. CRD42022379817). Despite varying patient selection methods, surgery plus chemotherapy demonstrated significantly prolonged progression-free survival compared to chemotherapy alone. However, overall survival outcomes were inconsistent: while GOG-0213 did not show extended overall survival, recent studies with stricter defined criteria for surgery (SOC-1 and DESKTOP-III) reported improved overall survival with the addition of surgery. Morbidity and mortality rates were low, with no difference in quality of life between the surgery and no-surgery groups. In conclusion, cytoreductive surgery presents a promising option for recurrent epithelial ovarian cancer treatment. Nonetheless, well-defined selection criteria appear crucial for achieving increased overall survival compared to conventional treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Chemotoxicity in colorectal cancer (CRC) patients impacts treatment compliance, survival, and quality of life. While clinician-reported chemotoxicity predicts rehospitalization and survival, a comprehensive understanding is lacking. This systematic review and meta-analysis studied chemotoxicity in CRC patients. The study found that 45.7% of patients experienced overall moderate-to-severe toxicities, with gastrointestinal toxicity (22.9%) and neuropathy or neutropenia (17.9%) being the most common. Risk factors included malnutrition, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low quality of life. Age was linked to neutropenia and gastrointestinal toxicity. Older adults had higher overall and gastrointestinal toxicities but lower neutropenia than younger adults. The study underscores the need for close monitoring and management of chemotoxicity in CRC patients. Community contributions have been instrumental in raising awareness about these issues, advocating for patient support, and future research to improve treatment toxicities in CRC. Background: Colorectal cancer (CRC) patients experience multiple types of chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine chemotoxicity's prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: −1.44) and GI toxicity (β:1.85) (p-values < 0.01). Older adults (>65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (p-values < 0.05). Conclusions. Our findings highlight the importance of closely monitoring and managing chemotoxicity in CRC patients receiving chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastomas (GBMs) are considered the most lethal cancer in the central nervous system (CNS), whose malignant phenotypes are majorly attributed to glioma stem cells (GSCs). Despite combined surgical radiotherapy with temozolomide chemotherapy and tumor-treating fields (TTFs), the tumor almost always recurs near the resection site. Besides the contribution of GSCs, the tumor microenvironment (TME) also plays an important role in glioma recurrence. Our work has demonstrated that GSC-derived exosomes carry lncRNA NEAT1 to promote the M2 polarization of glioma-associated macrophages (GAMs). Further mechanism exploration indicated that NEAT1 represses the expression of miR-125a in GAMs significantly. The decrease in miR-125a induces the elevation of target gene STAT3, which is required for macrophage M2 polarization. The development of M2-like GAMs contributes to the immunosuppressive microenvironment and glioma progression. Our findings elucidate the functions and mechanisms of the crosstalk between GSCs and GAMs via exosomes, providing new therapeutic targets and strategies for glioma. Glioblastoma (GBM), as the most common primary brain tumor, usually results in an extremely poor prognosis, in which glioma stem cells (GSCs) and their immunosuppressive microenvironment prominently intervene in the resistance to radiotherapy and chemotherapy that directly leads to tumor recurrence and shortened survival time. The specific mechanism through which exosomes generated from GSCs support the creation of an immunosuppressive microenvironment remains unknown, while it is acknowledged to be engaged in intercellular communication and the regulation of the glioma immunosuppressive microenvironment. The elevated expression of LncRNA-NEAT1 was found in glioma cells after radiotherapy, chemotherapy, and DNA damage stimulation, and NEAT1 could promote the malignant biological activities of GSCs. Emerging evidence suggests that lncRNAs may reply to external stimuli or DNA damage by playing a role in modulating different aspects of tumor biology. Our study demonstrated a promotive role of the carried NEAT1 by GSC-derived exosomes in the polarization of M2-like macrophages. Further experiments demonstrated the mediative role of miR-125a and its target gene STAT3 in NEAT1-induced polarization of M2-like macrophages that promote glioma progression. Our findings elucidate the mechanism by which GSCs influence the polarization of M2-like macrophages through exosomes, which may contribute to the formation of immunosuppressive microenvironments. Taken together, our study reveals the miR-125a-STAT3 pathway through which exosomal NEAT1 from treatment-resistant GSCs contributes to M2-like macrophage polarization, indicating the potential of exosomal NEAT1 for treating glioma. [ABSTRACT FROM AUTHOR]

Simple Summary: Taste and smell alterations (TSAs) are a distressing yet underdiagnosed side effect in cancer patients undergoing chemotherapy. However, long-term investigations using both questionnaires and chemosensory tests are scarce. We examined the prevalence of quantitative and qualitative TSAs, as well as their connection with clinical characteristics such as age, sex, anorexia, and neuropathy. We also compared patients receiving perpetual or temporary chemotherapy. All patients were examined up to five times within 12 to 24 months, commencing before the beginning of chemotherapy. We found TSAs in approximately 4 out of 5 patients during chemotherapy. The highest prevalence was documented among patients above 60 years of age as well as among those reporting anorexia or presenting signs of neuropathy. Post-therapy, taste and smell function recovered; however, scores did not reach baseline levels within 6 to 12 months. Future investigations will assess potential interventions to prevent or reduce TSAs. Previous data regarding chemotherapy-induced olfactory and gustatory dysfunction (CIOGD) are heterogeneous due to inconsistent study designs and small numbers of patients. To provide consistent, reliable data, we conducted a cohort study using standardized testing. Patients diagnosed with lymphoma, leukemia, or gastrointestinal malignancies were examined up to five times (T1 to T5), beginning prior to chemotherapy. We examined patients receiving temporary treatment up to 12 months post-therapy. Clinical assessment included extensive questionnaires, psychophysical tests of olfactory and gustatory function, and measurement of peripheral neuropathy. Statistical analysis included non-parametric tests to evaluate the longitudinal development of CIOGD. Our data (n = 108) showed a significant decline in olfactory and gustatory testing during chemotherapy (p-values < 0.001). CIOGD appeared stronger among patients above 60 years, while sex did not matter significantly. However, we identified distinct associations between CIOGD and reported anorexia as well as with higher neuropathy scores. Self-assessment appeared less sensitive to chemosensory dysfunction than psychophysical testing. Post-therapy, olfactory and gustatory function regenerated, though baseline levels were not attained within 6 to 12 months. In conclusion, our data highlight the wide prevalence and slow recovery of CIOGD. Understanding CIOGD as a potential neurotoxic effect may disclose new therapeutic prospects. [ABSTRACT FROM AUTHOR]

Background: Medicinal plant-mediated combinational therapies have gained importance globally due to minimal side effects and enhanced treatment outcomes compared to single-drug modalities. We aimed to analyze the cytotoxic potential of each conventional treatment i.e., photodynamic therapy (PDT), chemotherapy (doxorubicin hydrochloride; Dox-HCl) with or without various concentrations of medicinal plant extracts (PE) on soft tissue cancer Rhabdomyosarcoma (RD) cell line. Methods: The Rhabdomyosarcoma (RD) cell line was cultured and treated with Photosensitizer (Photosense (AlPc4)), Chemo (Dox-HCl), and their combinations with different concentrations of each plant extract i.e., Thuja occidentalis, Moringa oleifera, Solanum surattense. For the source of illumination, a Diode laser (λ = 630 nm ± 1 nm, Pmax = 1.5 mW) was used. Photosensitizer uptake time (∼ 45 min) was optimized through spectrophotometric measurements (absorption spectroscopy). Drug response of each treatment arm was assessed post 24 h of administration using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5- 5-diphenyl-2 H- tetrazolium bromide (MTT) assay. Results: PE-mediated Chemo-Photodynamic therapy (PDT) exhibited synergistic effects (CI < 1). Moreover, Rhabdomyosarcoma culture pretreated with various plant extracts for 24 h exhibited significant inhibition of cell viability however most effective outcomes were shown by low and high doses of Moringa oleifera compared to other plant extracts. Post low doses treated culture with all plant extracts followed by PDT came up with more effectiveness when compared to all di-therapy treatments. Conclusion: The general outcome of this work shows that the ethanolic plant extracts (higher doses) promote the death of cancerous cells in a dose-dependent way and combining Dox-HCl and photo-mediated photodynamic therapy can yield better therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer ranks 10th in the incidence rate of malignant tumors in male, and 12th in female. Pancreatic cancer is the sixth leading cause of tumor-related deaths in China. It is a devastating malignancy with poor prognosis. Methods: Driven by the concept of "integrated medicine", the China Anti-Cancer Association Committee of Pancreatic Cancer organized relevant experts to complete this guideline. Results: This guideline aims to guide the integrated treatment and rehabilitation management of pancreatic cancer in an all-round way based on "Preventing, Screening, Diagnosing, Treating, and Rehabilitating". Conclusions: We hope that this guideline will provide effective references for clinicians, so as to achieve the best treatment effects for pancreatic cancer patients in China. [ABSTRACT FROM AUTHOR]

Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resistance to chemotherapeutic drugs by regulating cell apoptosis, cell cycle, drug transport and metabolism, DNA damage repair, EMT, autophagy, cancer stem cell characteristics, and metabolic reprogramming. This indicates that NEAT1 may be an important target to overcome chemotherapy resistance and is expected to be a potential biomarker to predict the effect of chemotherapy. This article summarizes the expression characteristics and clinical characteristics of NEAT1 in different cancers, and deeply discusses the regulatory role of NEAT1 in cancer chemotherapy resistance and related molecular mechanisms, aiming to clarify NEAT1 as a new target to overcome cancer chemotherapy resistance and the feasibility of chemotherapy sensitizers, with a view to providing a potential therapeutic direction for overcoming the dilemma of cancer resistance in the future. [ABSTRACT FROM AUTHOR]

Uncovering acquired drug resistance mechanisms has garnered considerable attention as drug resistance leads to treatment failure and death in patients with cancer. Although several bioinformatics studies developed various computational methodologies to uncover the drug resistance mechanisms in cancer chemotherapy, most studies were based on individual or differential gene expression analysis. However the single gene-based analysis is not enough, because perturbations in complex molecular networks are involved in anti-cancer drug resistance mechanisms. The main goal of this study is to reveal crucial molecular interplay that plays key roles in mechanism underlying acquired gastric cancer drug resistance. To uncover the mechanism and molecular characteristics of drug resistance, we propose a novel computational strategy that identified the differentially regulated gene networks. Our method measures dissimilarity of networks based on the eigenvalues of the Laplacian matrix. Especially, our strategy determined the networks' eigenstructure based on sparse eigen loadings, thus, the only crucial features to describe the graph structure are involved in the eigenanalysis without noise disturbance. We incorporated the network biology knowledge into eigenanalysis based on the network-constrained regularization. Therefore, we can achieve a biologically reliable interpretation of the differentially regulated gene network identification. Monte Carlo simulations show the outstanding performances of the proposed methodology for differentially regulated gene network identification. We applied our strategy to gastric cancer drug-resistant-specific molecular interplays and related markers. The identified drug resistance markers are verified through the literature. Our results suggest that the suppression and/or induction of COL4A1, PXDN and TGFBI and their molecular interplays enriched in the Extracellular-related pathways may provide crucial clues to enhance the chemosensitivity of gastric cancer. The developed strategy will be a useful tool to identify phenotype-specific molecular characteristics that can provide essential clues to uncover the complex cancer mechanism. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is one of the most aggressive gastrointestinal malignancies, characterized by rapid progression and early onset of metastasis, leading to a dismal prognosis for patients. In the recent past, substantial progress has been conducted recently in managing PC, encompassing various treatment modalities such as chemotherapy, neoadjuvant therapy, targeted therapy, and immunotherapy. Particularly in 2023, several noteworthy studies have contributed to optimizing neoadjuvant treatment regimens and exploring novel approaches that involve targeted therapies and immunotherapies for PC. These advancements hold promise for improving overall survival outcomes and enhancing quality of life for patients with pancreatic cancer. This commentary summarizes the new advances in systemic therapy for pancreatic cancer in 2023. [ABSTRACT FROM AUTHOR]

Poly(ADP-ribose) polymerase (PARP) inhibitors are targeted therapies that accumulate DNA damage by interfering with DNA repair mechanisms and are approved for treating several cancers with BRCA1/2 mutations. In this study, we utilized CRISPR-dCas9 interference screening to identify genes regulating sensitivity to PARP inhibitors in breast cancer cell lines. Our findings indicated that the interferon (IFN) signaling gene IRF9 was critically involved in modulating sensitivity to these inhibitors. We revealed that the loss of IRF9 leads to increased resistance to the PARP inhibitor in MDA-MB-468 cells, and a similar desensitization was observed in another breast cancer cell line, MDA-MB-231. Further analysis indicated that while the basal expression of IRF9 did not correlate with the response to the PARP inhibitor olaparib, its transcriptional induction was significantly associated with increased sensitivity to the DNA-damaging agent cisplatin in the NCI-60 cell line panel. This finding suggests a mechanistic link between IRF9 induction and cellular responses to DNA damage. Additionally, data from the METABRIC patient tissue study revealed a complex network of IFN-responsive gene expressions postchemotherapy, with seven upregulated genes, including IRF9, and three downregulated genes. These findings underscore the intricate role of IFN signaling in the cellular response to chemotherapy. Collectively, our CRISPR screening data and subsequent bioinformatic analyses suggest that IRF9 is a novel biomarker for sensitivity to DNA-damaging agents, such as olaparib and platinum-based chemotherapeutic agents. Our findings for IRF9 not only enhance our understanding of the genetic basis of drug sensitivity, but also elucidate the role of IRF9 as a critical effector within IFN signaling pathways, potentially influencing the association between the host immune system and chemotherapeutic efficacy. [ABSTRACT FROM AUTHOR]

Decision-making regarding adjuvant chemotherapy for older adults with breast cancer is a challenge because older adult patients often have poor physical health, frailty, and age-related comorbidities, which can compromise treatment outcome. Due to these considerations, doctors tend to use less chemotherapy for breast cancer in older adults. However, older patients in good general health could still benefit from chemotherapy. Careful benefit-risk assessment is essential to provide best care for each older adult patient. Due to a rapidly aging population, breast cancer in older adults is becoming a serious public health issue in China. In this mini review, we discuss the need, means, and tools to assess the benefits and risks of adjuvant chemotherapy in older adults with breast cancer. The contents of this review may drive decision-making with regard to the use and selection of adjuvant chemotherapy for older adult patients in China who are fit for the treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: We evaluated the repurposing of a class of non-cancer drugs, phosphodiesterase inhibitors, to increase the potency of an anti-folate chemotherapy drug against non-small-cell lung cancer. We showed that this approach represents a double-edged strategy. While the use of phosphodiesterase inhibitors potentiated the killing of lung cancer cells by combination low-dose anti-folate chemotherapy, in half of the tumors evaluated, the benefit was lost when using higher doses of chemotherapy. Phosphosidesterases (PDEs) are key regulators of cyclic nucleotide signaling, controlling many hallmarks of cancer and playing a role in resistance to chemotherapy in non-small-cell lung cancer (NSCLC). We evaluated the anti-tumor activity of the anti-folate agent pemetrexed (PMX), alone or combined with biochemical inhibitors of PDE5, 8, 9, or 10, against squamous and non-squamous NCSLC cells. Genomic alterations to PDE genes (PDEmut) or PDE biochemical inhibition (PDEi) can sensitize NSCLC to PMX in vitro (observed in 50% NSCLC evaluated). The synergistic activity of PDEi with PMX required microdosing of the anti-folate drug. As single agents, none of the PDEis evaluated have anti-tumor activity. PDE biochemical inhibitors, targeting either cAMP or cGMP signaling (or both), resulted in significant cross-modulation of downstream pathways. The use of PDEi may present a new strategy to overcome PMX resistance of PDEwt NSCLC tumors but comes with important caveats, including the use of subtherapeutic PMX doses. [ABSTRACT FROM AUTHOR]

Simple Summary: Neoadjuvant chemotherapy in breast cancer facilitates breast and axillary surgery and offers significant prognostic value. We present a retrospective cohort of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans, plus antiHER2 in HER2-positive cases. The 10-year estimated disease free survival was 77.3% (95%CI 73.3–81.4%) and the Breast cancer specific survival 83.7% (95%CI 80.3–87.2%). The statistically independent factors related to patient survival were pathology subtype (lobular cancers HR, 4); molecular surrogate subtype (triple negative HR, 4); type of surgery (mastectomy HR, 2), response to chemotherapy (the risk incremented according to the residual cancer burden in 2.2, 4.4 and 8.0 times in I, II and III, respectively) and vascular invasion (HR, 2.4). BRCA carriers presented a longer survival, with an estimated 10 years DDFS of 89.6% vs. 77.2% for non-carriers, p = 0.054. Long-term outcomes after neoadjuvant chemotherapy can help patients and clinicians make well-informed decisions. Introduction: Neoadjuvant chemotherapy in breast cancer offers the possibility to facilitate breast and axillary surgery; it is a test of chemosensibility in vivo with significant prognostic value and may be used to tailor adjuvant treatment according to the response. Material and Methods: A retrospective single-institution cohort of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans, plus antiHEr2 in Her2-positive cases, was studied. Survival was calculated at 5 and 10 years. Kaplan–Meier curves with a log-rank test were calculated for differences according to age, BRCA status, menopausal status, TNM, pathological and molecular surrogate subtype, 20% TIL cut-off, surgical procedure, response to chemotherapy and the presence of vascular invasion. Results: The pCR rate was 25.3% and was greater in HER2 (51.3%) and TNBC (31.7%) and in BRCA carriers (41.9%). The factors independently related to patient survival were pathology and molecular surrogate subtype, type of surgery, response to NACT and vascular invasion. BRCA status was a protective prognostic factor without reaching statistical significance, with an HR 0.5 (95%CI 0.1–1.4). Mastectomy presented a double risk of distant recurrence compared to breast-conservative surgery (BCS), supporting BCS as a safe option after NACT. After a mean follow-up of 126 (SD 43) months, luminal tumors presented a substantial difference in survival rates calculated at 5 or 10 years (81.2% compared to 74.7%), whereas that for TNBC was 75.3 and 73.5, respectively. The greatest difference was seen according to the response in patients with pCR, who exhibited a 10 years DDFS of 95.5% vs. 72.4% for those patients without pCR, p < 0001. This difference was especially meaningful in TNBC: the 10 years DDFS according to an RCB of 0 to 3 was 100%, 80.6%, 69% and 49.2%, respectively, p < 0001. Patients with a particularly poor prognosis were those with lobular carcinomas, with a 10 years DDFS of 42.9% vs. 79.7% for ductal carcinomas, p = 0.001, and patients with vascular invasion at the surgical specimen, with a 10 years DDFS of 59.2% vs. 83.6% for those patients without vascular invasion, p < 0.001. Remarkably, BRCA carriers presented a longer survival, with an estimated 10 years DDFS of 89.6% vs. 77.2% for non-carriers, p = 0.054. Conclusions: Long-term outcomes after neoadjuvant chemotherapy can help patients and clinicians make well-informed decisions. [ABSTRACT FROM AUTHOR]

Simple Summary: Sacrectomy represents a radical indication for bone sarcomas (e.g., osteosarcoma or chondrosarcoma) and chordomas, as well as selected carcinomas with invasion of the sacrum. Extralesional en bloc excision is surgically demanding and associated with resection-induced neurologic deficits and risks. Due to the low incidence of bone sarcomas, the rare localization in the sacrum and the complexity of the surgical procedure, studies reporting on the oncological outcome and corresponding complications in larger patient numbers are rare. The aim was to describe the oncosurgical management and the complication profile and to analyze our own treatment results after partial/total sacrectomy, with attention paid to a possible benefit by using intraoperative 3D navigation. There was a significant difference in progression-free and metastasis-free survival between sarcoma, chordoma and carcinoma patients. Complications were common, but no independently influencing causative factors could be identified. Although there was a subjective impression of improved intraoperative 3D orientation and easier identification of resection planes, the use of navigation did not significantly influence resection status or oncological patient outcome. Introduction: Bone sarcoma or direct pelvic carcinoma invasion of the sacrum represent indications for partial or total sacrectomy. The aim was to describe the oncosurgical management and complication profile and to analyze our own outcome results following sacrectomy. Methods: In a retrospective analysis, 27 patients (n = 8/10/9 sarcoma/chordoma/locally recurrent rectal cancer (LRRC)) were included. There was total sacrectomy in 9 (incl. combined L5 en bloc spondylectomy in 2), partial in 10 and hemisacrectomy in 8 patients. In 12 patients, resection was navigation-assisted. For reconstruction, an omentoplasty, VRAM-flap or spinopelvic fixation was performed in 20, 10 and 13 patients, respectively. Results: With a median follow-up (FU) of 15 months, the FU rate was 93%. R0-resection was seen in 81.5% (no significant difference using navigation), and 81.5% of patients suffered from one or more minor-to-moderate complications (especially wound-healing disorders/infection). The median overall survival was 70 months. Local recurrence occurred in 20%, while 44% developed metastases and five patients died of disease. Conclusions: Resection of sacral tumors is challenging and associated with a high complication profile. Interdisciplinary cooperation with visceral/vascular and plastic surgery is essential. In chordoma patients, systemic tumor control is favorable compared to LRRC and sarcomas. Navigation offers gain in intraoperative orientation, even if there currently seems to be no oncological benefit. Complete surgical resection offers long-term survival to patients undergoing sacrectomy for a variety of complex diseases. [ABSTRACT FROM AUTHOR]