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Chemotherapy is one of the most effective treatments for cancer, but the efficacy of standard chemotherapy regimens is often limited by toxicities and the individual heterogeneity of cancers. Precise dosing is an important tool to improve efficacy and reduce significant differences in toxicity. However, most of the existing studies on chemotherapy optimization fail to fully consider the toxic side effects, drug resistance, and drug combinations, and thus the chemotherapy regimens obtained may face difficulty in achieving the expected efficacy and also affect the subsequent treatment. Therefore, this paper establishes a tumor growth model for the combination chemotherapy of cell cycle-specific and non-cycle-specific drugs and includes the factors of acquired drug resistance and toxic side effects, proposing an improved multi-objective Squirrel Search Algorithm, the TA-MOSSA, to solve the problem of accurate chemotherapy drug optimization. In this paper, experiments were conducted to analyze the efficacy of chemotherapy dosing regimens obtained by the TA-MOSSA based on the tumor growth model, and the results show that the TA-MOSSA can provide effective chemotherapy regimens for patients who take different treatment approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent advancements in cancer research have proven immunotherapies to be a promising strategy for the treatment of hematological malignancies. The bispecific antibody (BsAb) format was developed to overcome the issues of monoclonal antibody-based therapies. T-cell engagers (TCEs) are BsAbs, which directly activate T-cells and their anti-tumor features, ultimately resulting in the lysis of the targeted tumor cells. In 2014, the FDA approved blinatumomab for treatment of acute lymphoblastic leukemia. As of November 2023, seven clinically approved TCE therapies are on the market. In this paper, we summarized the technical basis of the TCE technology, its application in hematology, and its current issues and prospects. Recent advancements in cancer immunotherapy have made directing the cellular immune response onto cancer cells a promising strategy for the treatment of hematological malignancies. The introduction of monoclonal antibody-based (mAbs) targeted therapy has significantly improved the prognosis for hematological patients. Facing the issues of mAb-based therapies, a novel bispecific antibody (BsAb) format was developed. T-cell engagers (TCEs) are BsAbs, which simultaneously target tumor-associated antigens on tumor cells and CD3 molecules present on T-cells. This mechanism allows for the direct activation of T-cells and their anti-tumor features, ultimately resulting in the lysis of tumor cells. In 2014, the FDA approved blinatumomab, a TCE directed to CD3 and CD19 for treatment of acute lymphoblastic leukemia. Since then, numerous TCEs have been developed, allowing for treating different hematological malignancies such as acute myeloid leukemia, multiple myeloma, and non-Hodgkin lymphoma and Hodgkin lymphoma. As of November 2023, seven clinically approved TCE therapies are on the market. TCE-based therapies still have their limitations; however, improving the properties of TCEs, as well as combining TCE-based therapies with other forms of treatment, give hope to find the cures for currently terminal diseases. In this paper, we summarized the technical basis of the TCE technology, its application in hematology, and its current issues and prospects. [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancer is a common disease in urological patients. The approach to treatment depends on the severity of the tumor; in this article, we focus on tumors that do not invade the muscle layer of the bladder. Those tumors are resected during an endoscopic procedure (TURBT), but often reoccur. Treating bladder cancer with drugs instead of surgical removal of the bladder (radical cystectomy) is paramount for patients quality of life and overall well-being. The aim of this paper is to review methods of conservative treatment of tumors unresponsive to the typical treatment of choice (BCG instillations). Bladder cancer is the 10th most popular cancer in the world, and non-muscle-invasive bladder cancer (NMIBC) is diagnosed in ~80% of all cases. Treatments for NMIBC include transurethral resection of the bladder tumor (TURBT) and intravesical instillations of Bacillus Calmette-Guérin (BCG). Treatment of BCG-unresponsive tumors is scarce and usually leads to Radical Cystectomy. In this paper, we review recent advancements in conservative treatment of BCG-unresponsive tumors. The main focus of the paper is FDA-approved medications: Pembrolizumab and Nadofaragene Firadenovec (Adstiladrin). Other, less researched therapeutic possibilities are also included, namely: N-803 immunotherapy, TAR-200 and TAR-210 intravesical delivery systems and combined Cabazitaxel, Gemcitabine and Cisplatin chemotherapy. Conservative treatment and delaying radical cystectomy would greatly benefit patients' quality of life; it is undoubtedly the future of BCG-unresponsive NMIBC. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment options for patients with advanced renal cancer are limited, as one of the main methods, chemotherapy, is prone to drug resistance in the course of treatment. There have been numerous studies confirming that ferroptosis is involved in the development of renal cancer and drug resistance during treatment. In this review, we provide new insights into the resistance of classical chemotherapy drugs sorafenib and sunitinib in renal cancer and explore the mechanism of different types of ferroptosis-related drugs to treat renal cancer, such as herb extract medicine, ferroptosis inducers, natural compounds, nanomaterials, etc. We have also conducted an in-depth discussion on the application of ferroptosis-related drugs in the clinical treatment of renal cancer. Renal cancer is a common and serious malignant tumor of the urinary system. While surgery effectively treats early-stage renal cancer, advanced cases pose a significant challenge due to poor treatment outcomes and chemotherapy resistance. Therefore, there is an urgent need to develop alternative therapeutic strategies. Ferroptosis is a newly defined form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which plays a critical role in tumor progression and drug resistance. Recent studies have shown that ferroptosis is involved in the occurrence and development of renal cancer, and ferroptosis-related genes can induce cell apoptosis and can be used as potential biomarkers for early diagnosis of renal cancer and participate in drug resistance of renal cancer chemotherapy. With the continuous improvement of the mechanism of ferroptosis, drugs targeting ferroptosis for the treatment of renal cancer are emerging in an endless stream. Based on the theoretical basis of the occurrence of ferroptosis, this paper reviewed drug-induced ferroptosis in renal cancer cells from the aspects of herbal medicine, natural compounds, drug resistance mechanisms, and nanomaterials, and delves into the clinical application potential of ferroptosis-related drugs in the treatment of renal cancer. [ABSTRACT FROM AUTHOR]

Despite the introduction of targeted vaccines and screening protocols, locally advanced cervical cancer represents a median proportion of 37% among all cervical carcinomas. Compared to early stages, it presents significantly lower cure rates, with a 5-year disease-free survival rate of 68% and a 5-year overall survival rate of 74%. According to current guidelines, definitive radiotherapy with concomitant chemotherapy represents the gold standard for locally advanced cervical cancer treatment. However, a significant number of patients relapse and die from metastatic disease. The aim of this narrative review is to examine the recent advancements in treating locally advanced cervical cancer, exploring new frontiers in therapeutic approaches. The PubMed database and clinical trial registries were searched to identify relevant articles published on locally advanced cervical cancer treatment up to March 2024, mainly focusing on papers published in the last decade. Abstracts presented at major international congresses that bring relevant evidence were included. Progress achieved in refining radiotherapy techniques, recent evidence regarding neoadjuvant treatment preceding surgery or concurrent chemoradiotherapy, and key findings concerning adjuvant treatment are thoroughly explored. Furthermore, a comprehensive review of prominent phase II and phase III trials examining the integration of immune checkpoint inhibitors is conducted, analyzing the various contexts in which they are applied. In light of the new evidence that has emerged in recent years and is discussed in this article, the appropriate selection of the most suitable therapeutic approach for each patient remains a complex but crucial issue. [ABSTRACT FROM AUTHOR]

Interindividual variation in drug efficacy and toxicity is a significant problem, potentially leading to adverse clinical and economic public health outcomes. While pharmacogenetics and pharmacogenomics have long been considered the primary causes of such heterogeneous responses, pharmacomicrobiomics has recently gained attention. The microbiome, a community of microorganisms living in or on the human body, is a critical determinant of drug response and toxicity. Factors such as diet, lifestyle, exposure to xenobiotics, antibiotics use, illness, and genetics can influence the composition of the microbiota. Changes in the intestinal microbiota are particularly influential in drug responsiveness, especially in cancer chemotherapy. The microbiota can modulate an individual's response to a drug, affecting its bioavailability, clinical effect, and toxicity, affecting treatment outcomes and patient quality of life. For instance, the microbiota can convert drugs into active or toxic metabolites, influencing their efficacy and side effects. Alternatively, chemotherapy can also alter the microbiota, creating a bidirectional interplay. Probiotics have shown promise in modulating the microbiome and ameliorating chemotherapy side effects, highlighting the potential for microbiota-targeted interventions in improving cancer treatment outcomes. This opinion paper addresses how environmental factors and chemotherapy-induced dysbiosis impact cancer chemotherapy gastrointestinal toxicity. [ABSTRACT FROM AUTHOR]

The scientific literature was reviewed with the aim of analysing the state of the art on the role of nursing in the management of chemotherapy extravasation, recognising the possible risk factors and identifying effective training programmes for nurses. WOS, Scopus, and PubMed databases were used to perform the searches. Papers that met the inclusion criteria and that had been published in the last 9 years were selected. The Effective Public Health Practice Project (EPHPP) instrument was applied to the selected studies. In addition, this research was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (ID: 512480). Out of the 23 initially selected articles, a total of 9 articles were eventually included, since they met the eligibility criteria that were established after a more exhaustive analysis, which included reading their abstracts and full texts. The results show that the management of chemotherapy extravasation is closely related to factors that largely depend on the nursing staff. Among the most relevant findings are factors including the identification of the nursing role in the management of extravasation due to chemotherapy; risk factors; and effective training programmes for nursing. Nurses play a crucial role throughout the entire process of treatment, prevention, and health education in chemotherapy treatment. Training programmes for nurses are fundamental, as they increase their professional competence and improve the safety of the patient. Adequate knowledge of chemotherapy treatment and the risk factors of extravasation are basic elements for the prevention of this type of injury, as well as for the improvement of the quality of life of patients under this kind of intravenous therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Though chemotherapy is generally known to be effective in the fight against cancer, its application is associated with a number of side effects, including toxic impacts on the ovaries. The most ovotoxic cytostatic chemotherapeutics are the classical alkylating compounds, particularly cyclophosphamide. Thus, it is of utmost importance to find effective means to protect ovaries against the negative influence of chemotherapeutic agents. This review paper presents the results of the current research work on the hitherto proposed agents potentially protecting the functions and state of ovaries exposed to chemotherapy. A large body of promising results have been reported, but as presented, it is necessary to undertake thorough and comprehensive studies aimed at providing an explicit evaluation of the efficacy of selected ovoprotecting agents and their possible clinical use in the future. Chemotherapy is one of the leading cancer treatments. Unfortunately, its use can contribute to several side effects, including gynotoxic effects in women. Ovarian reserve suppression and estrogen deficiency result in reduced quality of life for cancer patients and are frequently the cause of infertility and early menopause. Classic alkylating cytostatics are among the most toxic chemotherapeutics in this regard. They cause DNA damage in ovarian follicles and the cells they contain, and they can also induce oxidative stress or affect numerous signaling pathways. In vitro tests, animal models, and a few studies among women have investigated the effects of various agents on the protection of the ovarian reserve during classic chemotherapy. In this review article, we focused on the possible beneficial effects of selected hormones (anti-Müllerian hormone, ghrelin, luteinizing hormone, melatonin), agents affecting the activity of apoptotic pathways and modulating gene expression (C1P, S1P, microRNA), and several natural (quercetin, rapamycin, resveratrol) and synthetic compounds (bortezomib, dexrazoxane, goserelin, gonadoliberin analogs, imatinib, metformin, tamoxifen) in preventing gynotoxic effects induced by commonly used cytostatics. The presented line of research appears to provide a promising strategy for protecting and/or improving the ovarian reserve in the studied group of cancer patients. However, well-designed clinical trials are needed to unequivocally assess the effects of these agents on improving hormonal function and fertility in women treated with ovotoxic anticancer drugs. [ABSTRACT FROM AUTHOR]

Every year, over 600,000 new cases of esophageal cancer are registered worldwide. Treatment depends on the stage of the disease. In the early stages, surgical treatment is the basis (T1–T2 lesion < 3 cm, N0M0), while in more advanced stages, surgical treatment is preceded by radiochemotherapy or only radiochemotherapy is used. In the case of generalized disease, the main treatments used are systemic treatments of chemotherapy, immunotherapy and palliative teleradiotherapy or brachytherapy. Brachytherapy can be used at virtually any stage of disease, both as a radical treatment and as a palliative treatment. This paper presents the possibilities of using brachytherapy at various stages of esophageal cancer treatment. Particular attention was paid to the role of combining brachytherapy and immunotherapy and the possibility of an abscopal effect. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is an aggressive brain cancer. Despite progress made in cancer research, patients diagnosed with glioblastomas continue to have a poor rate of survival. Lipidomics is a field of study that seeks to comprehend the structure and function of lipids, otherwise known as fats. Glioblastomas have demonstrated imbalance in lipids, and, therefore, lipidomics shows promise as an avenue to better understand glioblastomas. This paper reviews the literature on lipidomics in glioblastomas and suggests future directions for lipidomic research into the diagnosis, prognosis, and treatment of glioblastomas. Glioblastoma is the most aggressive primary brain malignancy in adults, and has a survival duration of approximately 15 months. First line treatment involves surgical resection, chemotherapy, and radiation, but despite the multi-pronged approach and advances in cancer research, glioblastoma remains devastating with a high mortality rate. Lipidomics is an emerging discipline that studies lipid pathways and characteristics, and is a promising field to understand biochemical mechanisms. In glioblastoma, disrupted lipid homeostasis has been reported in the literature. A thorough understanding of serum lipidomics may offer ways to better understand glioblastoma biomarkers, prognosis, and treatment options. Here, we review the literature, offering future directions for lipidomics research in glioblastomas. [ABSTRACT FROM AUTHOR]

Simple Summary: This article summarises the international Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial for patients with rhabdomyosarcoma. The trial has multiple research questions relating to chemotherapy and radiotherapy and biological and imaging studies as well as to the introduction of novel drugs for patients with very high-risk disease. The rationale, background, and international collaboration of the trial are explained, and how the data will be used to inform future studies is outlined. The Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial is an overarching, multinational study for children and adults with rhabdomyosarcoma (RMS). The trial, developed by the European Soft Tissue Sarcoma Study Group (EpSSG), incorporates multiple different research questions within a multistage design with a focus on (i) novel regimens for poor prognostic subgroups, (ii) optimal duration of maintenance chemotherapy, and (iii) optimal use of radiotherapy for local control and widespread metastatic disease. Additional sub-studies focusing on biological risk stratification, use of imaging modalities, including [18F]FDG PET-CT and diffusion-weighted MRI imaging (DWI) as prognostic markers, and impact of therapy on quality of life are described. This paper forms part of a Special Issue on rhabdomyosarcoma and outlines the study background, rationale for randomisations and sub-studies, design, and plans for utilisation and dissemination of results. [ABSTRACT FROM AUTHOR]

Simple Summary: Undifferentiated embryonal sarcoma of the liver is a rare pediatric tumor with a traditionally poor prognosis. Dual treatment with a combination of surgery and chemotherapy has produced much improved outcomes. The sharing and consolidation of various case series and clinical experiences allow for the prompt design of appropriate treatment advice. Even in the event of unresectable or recurrent diseases, other treatment modalities such as orthotopic liver transplantation and radiotherapy can be offered. This review of treatment recommendations for rare undifferentiated embryonal sarcoma of the liver has important clinical use. Undifferentiated embryonal sarcoma of the liver is a rare mesenchymal tumor with a highly malignant potential. It occurs almost exclusively in the pediatric population and typically has a poor outcome. Although previous studies have reported dismal prognoses, recent advances in combined treatment modalities, e.g., surgery and chemotherapy, have given cause for optimism. Even in those diseases not amenable to complete surgical resection or refractory diseases, other treatment modalities, such as liver transplant, have yielded promising results. This paper provides a review of the current treatment modalities for hepatic undifferentiated embryonal sarcoma in children. [ABSTRACT FROM AUTHOR]

Simple Summary: Cholangiocarcinoma (CCA) manifests as a complex interplay of genetic and environmental factors, necessitating personalized approaches. This review covers the various causes, risk factors, and molecular aspects of CCA in oncology. It explores current diagnostic methods and treatments, such as targeted therapies and immunotherapy. Additionally, it addresses emerging strategies like microbiota modulation and the use of natural compounds. This review paper provides a comprehensive understanding of CCA, offering insights into current and evolving approaches for effective interventions in oncological care. Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the advances in medicine, the 5-year survival rate for pancreatic ductal adenocarcinoma (PDAC) is still dismal and has not improved. New treatment options are required. Some data have been promising for endoscopic ultrasound-guided phosphorus-32 (32P) microparticle implantation. Given the role of poor vascularisation in the poor response of pancreatic cancer to standard therapy, such as chemotherapy, we hypothesised that EUS-guided 32P microparticle implantation improves chemotherapy delivery to and effects on the primary tumour. No treatment option has been shown to consistently improve tumour vascularity in PDAC, but a treatment that is able to improve vascularity may work synergistically with chemotherapy to improve outcomes in PDAC. Background: Poor intra-tumoural vascularity contributes to a lack of response to chemotherapy in pancreatic cancers. Preliminary data suggest that the addition of endoscopic ultrasound (EUS)-guided intra-tumoural injection of phosphorus-32 (32P) microparticles to standard chemotherapy is potentially beneficial in locally advanced pancreatic cancer (LAPC). We aimed to assess changes in pancreatic tumour vascularity following 32P implantation, using contrast-enhanced EUS (CE-EUS). Methods: This was a prospective single-centre trial from January 2022 to 2024 of patients with unresectable, non-metastatic LAPC undergoing standard FOLFIRINOX chemotherapy and 32P implantation. We performed CE-EUS pre-implantation after two chemotherapy cycles and 4 and 12 weeks after implantation. Time–intensity curves were analysed for 90 s after IV contrast bolus to ascertain peak intensity and intensity gain. Results: A total of 20 patients underwent 32P implantation, with 15 completing 12-week follow-up. The technical success of 32P implantation was 100%. The median primary tumour size reduced from 32 mm (IQR 27.5–38.75) pre-implantation to 24 mm (IQR 16–26) 12 weeks post-implantation (p < 0.001). Five patients (25%) had tumour downstaging, and four underwent resections. The baseline (pre-implantation, post-chemotherapy) median intensity gain of contrast enhancement within the tumour was 32.15 (IQR 18.08–54.35). This increased to 46.85 (IQR 35.05–76.6; p = 0.007) and 66.3 (IQR 54.7–76.3; p = 0.001) at 4 weeks and 12 weeks post-implantation, respectively. Over a median follow-up of 11.2 months (IQR 7.8–12.8), 15/20 (75%) of patients remained alive, with 3/20 (15%) demonstrating local disease progression. Overall survival was not significantly different between patients with or without an increased intensity of 10 a.u. or more at 12 weeks post-implantation. Conclusion: This is the first clinical study to demonstrate treatment-induced increased vascularity within pancreatic primary tumours, which followed 32P implantation and FOLFIRINOX chemotherapy. Larger comparative trials are warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Nodal peripheral T-cell lymphomas (PTCLs) are among the most aggressive lymphomas and in the majority of cases are considered incurable. Therefore, there is a cogent need for novel therapies. In this review, the authors analyzed the biological rationale, the experimental experience, and the real-world data concerning the use of histone deacetylase inhibitors (HDACis) to treat PTCLs. Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphomas (PTCLs), a heterogeneous group of aggressive malignancies with an unfavorable prognosis. Recent evidence has shown that HDACis are effective in treating PTCL, especially in cases where the disease has relapsed or is resistant to conventional treatments. Several clinical trials have demonstrated that HDACis, such as romidepsin and belinostat, can elicit long-lasting positive outcomes in individuals with PTCLs, either when used alone or in conjunction with conventional chemotherapy. They exert their anti-tumor effects by regulating gene expression through the inhibition of histone deacetylases, which leads to cell cycle arrest, induction of programmed cell death, and,the transformation of cancerous T cells, as demonstrated by gene expression profile studies. Importantly, besides clinical trials, real-world evidence indicated that the utilization of HDACis presents a significant and beneficial treatment choice for PTCLs. However, although HDACis showed potential effectiveness, they could not cure most patients. Therefore, new combinations with conventional drugs as well as new targeted agents are under investigation. [ABSTRACT FROM AUTHOR]

Fifty-two years have passed since President Nixon launched the "War on Cancer". Despite unparalleled efforts and funds allocated worldwide, the outlined goals were not achieved because cancer treatment approaches such as chemotherapy, radiation therapy, hormonal and targeted therapies have not fully met the expectations. Based on the recent literature, a new direction in cancer therapy can be proposed which targets connections between cancer cells and their microenvironment by chemical means. Cancer–stromal synapses such as immunological synapses between cancer and immune cells provide an attractive target for this approach. Such synapses form ligand–receptor clusters on the interface of the interacting cells. They share a common property of involving intercellular clusters of spatially proximate and cooperatively acting proteins. Synapses provide the space for the focused intercellular signaling molecules exchange. Thus, the disassembly of cancer–stromal synapses may potentially cause the collapse of various tumors. Additionally, the clustered arrangement of synapse components offers opportunities to enhance treatment safety and precision by using targeted crosslinking chemical agents which may inactivate cancer synapses even in reduced concentrations. Furthermore, attaching a cleavable cell-permeable toxic agent(s) to a crosslinker may further enhance the anti-cancer effect of such therapeutics. The highlighted approach promises to be universal, relatively simple and cost-efficient. We also hope that, unlike chemotherapeutic and immune drugs that interact with a single target, by using supramolecular large clusters that include many different components as a target, the emergence of a resistance characteristic of chemo- and immunotherapy is extremely unlikely. [ABSTRACT FROM AUTHOR]

Background: Less than 25% of gastric cancers (GC) are discovered early, leading to limited treatment options and poor outcomes (27.8% mortality, 3.7% 5-year survival). Screening programs have improved cure rates, yet post-diagnosis treatment guidelines remain unclear (systemic chemotherapy versus surgery). The optimal type of palliative surgery (palliative gastrectomy (PG), surgical bypass (SB), endoscopic stenting (ES)) for long-term outcomes is also debated. Methods: A literature review was conducted using PubMed, MEDLINE, and EMBASE databases along with Google Scholar with the search terms "gastric cancer" and "palliative surgery" for studies post-1985. From the initial 1018 articles, multiple screenings narrowed it to 92 articles meeting criteria such as "metastatic, stage IV GC", and intervention (surgery or chemotherapy). Data regarding survival and other long-term outcomes were recorded. Results: Overall, there was significant variation between studies but there were similarities of the conclusions reached. ES provided quick symptom relief, while PG showed improved overall survival (OS) only with adjuvant chemotherapy in a selective population. PG had higher mortality rates compared to SB, with ES having a reported 0% mortality, but OS improved with chemotherapy across both SB and PG. Conclusions: Less frail patients may experience an improvement in OS with palliative resection under limited circumstances. However, operative intervention without systemic chemotherapy is unlikely to demonstrate a survival benefit. Further research is needed to explore any correlations. [ABSTRACT FROM AUTHOR]

Simple Summary: The primary treatment for operable pancreatic cancer involves surgery followed by adjuvant therapy, with an increasing use of perioperative or neoadjuvant chemotherapy. We performed a network meta-analysis to assess the comparative efficacy of various treatment approaches for resectable pancreatic cancer. A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone. Excluding Asian studies, the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen. The findings endorse the utilization of perioperative and multi-agent chemotherapy as the favored intervention for operable PC in Western nations. The primary treatment for operable pancreatic cancer (PC) involves surgery followed by adjuvant therapy. Nevertheless, perioperative or neoadjuvant chemotherapy (CT) may be used to mitigate the likelihood of recurrence and mortality. This network meta-analysis (NMA) assesses the comparative efficacy of various treatment approaches for resectable PC. A thorough search was carried out on January 31, 2023, encompassing PubMed/MEDLINE, Cochrane Library, and Embase databases. We incorporated randomized clinical trials (RCTs) that compared surgical interventions with or without (neo)adjuvant or perioperative therapies for operable PC. We conducted a fixed-effects Bayesian NMA. We presented the effect sizes in terms of hazard ratios (HRs) for overall survival (OS) along with 95% credible intervals (95% CrIs). The treatment was deemed statistically superior when the 95% credible interval (CrI) did not encompass a null value (hazard ratio < 1). Treatment rankings were established based on the surface under the cumulative ranking curve (SUCRA). A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone, with HRs ranging from 0.38 for perioperative treatments to 0.73 for adjuvant 5-fluorouracil. After the exclusion of studies conducted in Asia, it was found that the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen (SUCRA, p = 0.99). The findings endorse the utilization of perioperative CT, especially multi-agent CT, as the favored intervention for operable PC in Western nations. [ABSTRACT FROM AUTHOR]

Simple Summary: In the era of precision medicine and immunotherapy, the isolation and characterization of exosomes from the peripheral blood mononuclear cells (PBMC-EXs) of SCLC patients may represent a new tool to define responder (BR) from non-responder (NR) patients undergoing chemoimmunotherapy treatment. In this proof-of-concept study, we isolated PBMC-EXs from the peripheral blood of SCLC patients and investigated the potential role of such extracellular vesicles (EVs) in monitoring tumor response to drug stimuli. Interestingly, we found increased exosome levels of c-Myc and Snail along with reduced levels of the immune markers MAVS and STING in NR patients. Also, we showed that PBMC-EXs from BR patients induced an increase in apoptosis and a reduction in the cell viability of SCLC cells compared to PBMC-EXs from NR SCLC patients. Thus, we suggest that PBMC-EXs may represent an innovative strategy to be further explored for the therapy and selection of immune-responsive SCLC patients. Small cell lung cancer (SCLC) is a highly invasive and rapidly proliferating lung tumor subtype. Most patients respond well to a combination of platinum-based chemotherapy and PD-1/PDL-1 inhibitors. Unfortunately, not all patients benefit from this treatment regimen, and few alternative therapies are available. In this scenario, the identification of new biomarkers and differential therapeutic strategies to improve tumor response becomes urgent. Here, we investigated the role of exosomes (EXs) released from the peripheral blood mononuclear cells (PBMCs) of SCLC patients in mediating the functional crosstalk between the immune system and tumors in response to treatments. In this study, we showed that PBMC-EXs from SCLC patients with different responses to chemoimmunotherapy showed different levels of immune (STING and MAVS) and EMT (Snail and c-Myc) markers. We demonstrated that PBMC-EXs derived from best responder (BR) patients were able to induce a significant increase in apoptosis in SCLC cell lines in vitro compared to PBMC-EXs derived from non-responder (NR) SCLC patients. PBMC-EXs were able to affect cell viability and modulate apoptotic markers, DNA damage and the replication stress pathway, as well as the occurrence of EMT. Our work provides proof of concept that PBMC-EXs can be used as a tool to study the crosstalk between cancer cells and immune cells and that PBMC-EXs exhibit an in vitro ability to promote cancer cell death and reduce tumor aggressiveness. [ABSTRACT FROM AUTHOR]

Simple Summary: When we consider nutrition in patients with head and neck cancer (HNC), we mostly focus on the type of nutrition; studies on the type of nutrition at different time points are sparse. This retrospective study analyzed patients with HNC according to their nutritional status and association with percutaneous endoscopic gastrostomy (PEG) from admission to six months after treatment at a tertiary hospital in Germany from 2017 to 2019. Results showed that 14.9% required PEG before starting therapy. The need for PEG increased to 22.7% at six weeks after therapy and remained stable at 23% six months later. PEG placement was more frequently required for alcohol or nicotine use, oropharyngeal and hypopharyngeal carcinoma, squamous cell carcinoma, cancer stage III/IV, chemotherapy and impaired feeding. There has been an increase in the percentage of PEG over the observation period. This retrospective monocentric cohort study analyzed patients with head and neck cancer according their nutritional status and association of percutaneous endoscopic gastrostomy (PEG) from admission to six months after treatment at a tertiary hospital in Germany from 2017 to 2019. A total of 289 patients (76.5% men; median age 62 years; 63.3% stage IV) were included. Univariate analyses and ANOVAs with repeated measures were performed to analyze differences over time. The percentage of patients requiring PEG was 14.9% (43 of 289 patients) before start of treatment (Z0), 14% (40 of 286 patients alive) after one week (Z1), 22.7% (58 of 255 patients) after six weeks (Z2) and 23% (53 of 230 patients) after six months (Z3) from the end of treatment. PEG placement was associated with alcohol or nicotine consumption, in oropharyngeal and hypopharyngeal carcinoma, squamous cell carcinoma, cancer stage III/IV, chemotherapy and impairment of food intake (all p < 0.05). Weight loss between Z1 and Z3 with PEG did not differ from patients without PEG at Z0 (p = 0.074), although patients with PEG at Z0 had a lower mean weight at the beginning. PEG was important for a quarter of the patients alive at Z3 and helped to prevent weight loss. [ABSTRACT FROM AUTHOR]

Simple Summary: Conventional cancer treatments, based on chemotherapy and radiotherapy, are often effective but suffer from serious side effects and a potential risk of resistance. Dual therapies, combining DNA alkylating agents and antimicrobial peptides, are generating great interest. Within chemotherapies, a frequently used mechanism is DNA alkylation, inducing DNA damage and subsequent cell death. Antimicrobial peptides, in turn, have demonstrated their efficacy as anticancer agents due to their ability to selectively alter cancer cell membranes. In this review, our aim has been to explore the synergistic potential of these two therapeutic modalities when used together. Cancer remains one of the most difficult diseases to treat, requiring continuous research into innovative therapeutic strategies. Conventional treatments such as chemotherapy and radiotherapy are effective to a certain extent but often have significant side effects and carry the risk of resistance. In recent years, the concept of dual-acting therapeutics has attracted considerable attention, particularly the combination of DNA alkylating agents and antimicrobial peptides. DNA alkylation, a well-known mechanism in cancer therapy, involves the attachment of alkyl groups to DNA, leading to DNA damage and subsequent cell death. Antimicrobial peptides, on the other hand, have been shown to be effective anticancer agents due to their ability to selectively disrupt cancer cell membranes and modulate immune responses. This review aims to explore the synergistic potential of these two therapeutic modalities. It examines their mechanisms of action, current research findings, and the promise they offer to improve the efficacy and specificity of cancer treatments. By combining the cytotoxic power of DNA alkylation with the unique properties of antimicrobial peptides, dual-action therapeutics may offer a new and more effective approach to fighting cancer. [ABSTRACT FROM AUTHOR]

Background: Check-Mate 274 has demonstrated the disease-free survival (DFS) benefit of adjuvant nivolumab in surgically treated muscle-invasive bladder cancer (MIBC). Since immunotherapy represents an expensive treatment with potential side effects, a better understanding of patient-specific risks of disease progression might be useful for clinicians when weighing the indication for adjuvant nivolumab. Objective: To identify the criteria for risk stratification of disease progression among MIBC patients eligible for adjuvant nivolumab. Materials and methods: A single-institution, prospectively maintained database was queried to identify patients eligible for adjuvant nivolumab according to Check-Mate 274 criteria. To account for immortal bias, patients who died or were lost to follow-up within 3 months of undergoing a radical cystectomy (RC) were excluded. Kaplan–Meier and Cox regression analyses addressed DFS, defined as the time frame from diagnosis to the first documented recurrence or death from any cause, whichever occurred first. Regression tree analysis was implemented to identify criteria for risk stratification. Results: Between 2011 and 2022, 304 patients were identified, with a median follow-up of 50 (IQR 24–72) months. After multivariable adjustment, including NAC as a potential confounder, higher CCI (HR 1.56, 95%CI 1.10–2.21, p = 0.013), T stage (HR 2.06, 95%CI 1.01–4.17, p = 0.046), N stage (HR 1.73, 95%CI 1.26–2.38, p = 0.001) and presence of LVI (HR 1.52, 95%CI 1.07–2.15, p = 0.019) increased the risk of disease recurrence or death. Finally, a two-tier classification was developed. Here, five-year DFS rates were 56.1% vs. 18.1 for low vs. high risk (HR: 2.54, 95%CI 1.79–3.62, p < 0.001). Conclusions: The current risk classification, if externally validated on larger samples, may be useful when weighing the risk and benefit of adjuvant nivolumab treatment and making patients more aware about their disease and about the need for additional treatment after RC. [ABSTRACT FROM AUTHOR]

Background: Despite advancements in cancer treatment, chemotherapy side effects significantly impact patients both physically and emotionally. While pharmacological treatments can mitigate these side effects, they may trigger additional side effects, exacerbating the overall discomfort experienced by patients; moreover, psychological factors influencing physical symptoms are beyond the reach of pharmacological interventions. Nonpharmacological interventions, however, offer the potential for complementary or alternative solutions. Objectives: This review aims to offer a comprehensive analysis of the literature on the effectiveness of nonpharmacological interventions in managing the physical side effects of chemotherapy. Methods: This review, based on a search of PubMed, PsycINFO, and Web of Science databases, identified 46 relevant studies. It categorizes interventions and evaluates their effectiveness in managing common chemotherapy side effects (fatigue, nausea, pain, diarrhea, and constipation). Results: Guided imagery, tailored exercises, and Qigong show promise in reducing fatigue, while interventions like yoga and cognitive-behavioral approaches address nausea and vomiting. Pain benefits result from guided imagery and educational interventions. Limited evidence exists for diarrhea and constipation interventions, necessitating further research. Conclusions: This review offers provisional conclusions, emphasizing the potential of integrating evidence-based nonpharmacological approaches alongside pharmacological interventions to enhance patient outcomes and reduce chemotherapy-induced side effects, considering factors such as accessibility, safety, customization, and adaptability in clinical settings. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third leading cause of cancer-related deaths, and the five-year survival rate of the metastatic disease is less than 15%. Treatment approaches include surgery, systemic chemotherapy and radiotherapy. The aggressive nature and low five-year survival rate of metastatic colorectal cancer indicate a need for new treatment options to help combat this disease. Ursolic acid is a pentacyclic triterpenoid naturally occurring in many plants, with high concentrations found in cranberries. This review summarizes evidence from the last ten years of the effects of ursolic acid on colorectal cancer. Overall, the available studies indicate that the treatment of colon cancer cells with ursolic acid results in a significant inhibition of proliferation and induction of apoptosis. In addition, the limited in vivo studies indicate a significant reduction in tumor volume and tumor angiogenesis in animal models of colorectal cancer administered ursolic acid. More in vivo animal studies are required to better understand the potential anticancer properties of ursolic acid and to form the basis for human clinical trials. [ABSTRACT FROM AUTHOR]

Ovarian cancer is one of the most frequent malignancies in women. The treatment landscape underwent significant changes as new agents were introduced in ovarian cancer management over the last decade. We present two cases of long responses to Olaparib in BRCA (BReast CAncer gene) mutant ovarian cancer patients. The first case belongs to a 42-year-old female diagnosed with advanced ovarian carcinoma with a rare germinal mutation (BRCA1 c.68_69delAG, commonly found in descendants of Ashkenazi Jewish populations, but also Arabic and Asian ones) and a significant family history of ovarian and breast cancers. After poorly tolerated neoadjuvant chemotherapy, the patient underwent total hysterectomy, bilateral adnexectomy, and intraperitoneal hyperthermic chemotherapy. After eight months, the disease progressed, and first-line platinum chemotherapy was administered. Although not well-tolerated (grade 3 anemia, allergic reactions), chemotherapy resulted in a partial response, and given the patient's characteristics, maintenance with Olaparib was recommended. Treatment is ongoing (total current duration 69 months) and tolerated well (grade 1 side effects). This case illustrates the long-term benefits that novel therapies like Olaparib may offer in patients with platinum-sensitive relapsed ovarian cancer harboring a rare BRCA mutation. The second case highlights a 55-year-old postmenopausal woman diagnosed with ovarian cancer, FIGO stage IVA. Initial treatment included six cycles of chemotherapy, which led to a partial response, followed by interval debulking surgery and another four cycles of chemotherapy. Subsequent Olaparib maintenance therapy post BRCA1 mutation identification contributed to a significant progression-free survival of 65 months until disease recurrence and secondary cytoreductive surgery, showcasing the effectiveness of PARP inhibitors in personalized oncology treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: In-transit metastases (ITM) are a challenging aspect of advanced melanoma, traditionally treated with surgery. However, recent advances in systemic therapies, such as immune checkpoint inhibitors and targeted treatments, have significantly improved patient outcomes. These modern therapies are now often preferred over surgery alone. This article reviews the benefits of combining systemic and locoregional treatments, highlighting their potential to enhance survival and quality of life for patients with ITM. By integrating these approaches, we aim to provide a comprehensive strategy for optimizing melanoma treatment outcomes. In-transit metastases (ITM) in melanoma present a significant therapeutic challenge due to their advanced stage and complex clinical nature. From traditional management with surgical resection, ITM treatment has evolved with the advent of systemic therapies such as immune checkpoint inhibitors and targeted therapies, which have markedly improved survival outcomes. This study aims to review and highlight the efficacy of both systemic and locoregional treatment approaches for ITM. Methods include a comprehensive review of clinical studies examining the impact of treatments like immune checkpoint inhibitors, targeted therapies, Isolated Limb Perfusion, and electrochemotherapy. The results indicate that combining systemic therapies with locoregional treatments enhances both local disease control and overall survival rates. The introduction of modern immunotherapies has not diminished the effectiveness of locoregional therapies but rather improved patient outcomes when used in conjunction. The conclusions emphasize that a multidisciplinary approach integrating systemic and locoregional therapies offers a promising strategy for optimizing the management of ITM in melanoma patients. This integrated treatment model not only improves survival rates but also enhances the quality of life for patients, suggesting a shift in standard care practices toward more comprehensive therapeutic regimens. [ABSTRACT FROM AUTHOR]

Introduction: Current guidelines endorse the use of perioperative chemotherapy (POC) in muscle-invasive bladder cancer (MIBC) to enhance the long-term overall survival (OS) compared to radical cystectomy (RC) alone. This study aims to assess the impact of POC on the OS in frail and morbid (F-M) patients undergoing RC. Methods: A retrospective multicenter study of 291 patients who underwent RC between 2015 and 2019 was performed. Patients with both a Charlson comorbidity index ≥ 4 and Modified Frailty Index ≥ 2 were classified as the F-M cohort. We compared the clinical and pathological characteristics and outcomes of the F-M patients who received POC to those who underwent RC alone. Univariable and multivariable analyses were performed to identify the predictors of the OS. Results: The F-M cohort included 102 patients. POC was administered to 44% of these patients: neoadjuvant (NAC) to 31%, adjuvant (AC) to 19%, and both to 6 (6%). The OS was significantly lower in the F-M cohort compared to in the healthier patients (median OS 42 months, p = 0.02). The F-M patients who received POC were younger, less morbid and had better renal function. Although POC was marginally associated with improved OS in the univariable analysis (p = 0.06), this was not significant in the multivariable analysis (p = 0.50). NAC was associated with improved OS in the univariable analysis (p = 0.004) but not after adjustment for competing factors (p = 1.00). AC was not associated with the OS. Conclusions: POC does not improve the OS in F-M patients undergoing RC. Personalized treatment strategies and further prospective studies are needed to optimize care in this unique vulnerable population. [ABSTRACT FROM AUTHOR]

Background/Objectives: Wilms tumor (WT) is the most common form of pediatric renal tumor, accounting for over 90% of cases followed by hypernephroma. Some pediatric patients with WT (10%) experience relapse or metastasis and have poor survival rates. PD-L1 assists cancer cells in escaping damage from the immune system. P53 mutations are found in relapsed WT tumor samples. We hypothesized that testing circulating PD-1 and PD-L1 and P53 expression levels could offer a simple method to predict patient relapse and explore novel treatments for pediatric WTs and hypernephroma. Methods: Flow cytometric detection of cPD-1, cPD-L1, and P53 expression in relapsed and in-remission WT and hypernephroma before and after one year of chemotherapy was performed. Results: Our data shows increased levels of cPD-L1 in relapsed pediatric patients with WT or hypernephroma before and after chemotherapy. There were also slight and significant increases in cPD-1 levels in relapsed groups before chemotherapy. Additionally, we observed significant decreases in P53 expression after one year of chemotherapy in relapsed pediatric patients. Conclusions: Our study found that circulating PD-L1 can be used as a predictor marker for WT and hypernephroma relapse. In conclusion, these circulating markers can assist in monitoring relapse in WT and hypernephroma patients without the need for several biopsies. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms that primarily affect adults, with pediatric cases constituting only 0.5–2.7% of the total. Pediatric GISTs present unique clinical, genetic, and pathological features that distinguish them from adult cases. This literature review aims to elucidate these differences, emphasizing diagnostic and therapeutic challenges. We discuss the resistance of pediatric GISTs to conventional chemotherapy and highlight the importance of surgical intervention, especially in emergency situations involving intra-abdominal bleeding. The review also explores the molecular characteristics of pediatric GISTs, including rare mutations such as quadruple-negative wild-type GIST with an FGF3 gene gain mutation. To illustrate these points, we conclude with a case from our clinic involving a 15-year-old female with multiple CD117-positive gastric GISTs and a quadruple-negative wild-type genetic profile who required urgent surgical intervention following a failed tumor embolization. This case underscores the critical need for early diagnosis and individualized therapeutic strategies combining oncologic and surgical care to improve outcomes in pediatric GIST patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Canine inflammatory mammary carcinoma is an aggressive and painful type of mammary gland cancer in dogs, often leading to poor quality of life and short survival times. This study investigated the effectiveness of a treatment combining two drugs, toceranib and carprofen, as a first-line therapy for 15 dogs diagnosed with this condition. The aim was to evaluate both the cancer's response to the treatment and any improvements in the dogs' quality of life. The results showed that while no measurable responses were observed, 60% of the dogs experienced stabilization of the disease. Importantly, there were significant improvements in the dogs' overall well-being, including reduced pain and better mobility, appetite, and happiness. The median progression-free survival and the overall survival time were of 76 and 90 days, respectively, which is a notable outcome for such a severe condition. These findings suggest that this drug combination can provide meaningful relief and extend life for dogs suffering from inflammatory mammary carcinoma, offering hope and better management options for pet owners and veterinarians dealing with this challenging disease. Canine inflammatory mammary carcinoma (IMC) is an aggressive and rare type of mammary gland cancer in dogs where vascular endothelial growth factor and cyclooxigenase-2 overexpression usually occur, which contribute to its invasive and angiogenic nature. This study aimed to evaluate the efficacy and safety of a combined treatment regimen of toceranib phosphate and carprofen in dogs with measurable IMC. Fifteen female dogs with histopathologically confirmed IMC were included, undergoing a regimen of toceranib (2.4–2.75 mg/kg PO, three times weekly) and carprofen (4.4 mg/kg/24 h PO). Initial evaluations included physical exams, tumor measurements, complete blood count, biochemistry, urinalysis, three view thoracic radiographs, and abdominal ultrasound. Follow-up assessments of physical condition and quality of life (QOL) were conducted bi-weekly, with tumor response evaluations monthly, using RECIST v1.0 criteria. While no complete or partial responses were observed, 60% of the dogs maintained stable disease, with a median progression-free survival of 76 days and an overall survival of 90 days. Notably, 60% of the dogs showed clinical benefit through improved QOL and disease stabilization. The treatment was well-tolerated, with only grade I/II toxicities reported. Despite limited biological activity against the cancer, this protocol may enhance QOL in dogs with IMC, offering a valuable palliative option. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate atrial involvement by comparing pre- and post-chemotherapy left atrial mechanical and electromechanical parameters in patients treated with cardiotoxic chemotherapeutic agents. Methods: We designed our study as a prospective cohort study. Sixty-eight female patients between the ages of 18 and 50, scheduled for treatment with cardiotoxic chemotherapeutic agents, were included in our study. Atrial mechanical functions and electromechanical parameters were examined and compared with basic echocardiographic parameters before and after chemotherapy. Results: The mean age of the patients was 41.6 ± 7.9 years. After chemotherapy, lateral PA, septal PA, and tricuspid PA durations showed a significant increase (p < 0.001), but there were no statistically significant changes in the left intra-atrial electromechanical delay, the right intra-atrial electromechanical delay, or the interatrial electromechanical delay values. Following treatment, LAVmax, LAVmin, and LApreA significantly increased (p < 0.001). Additionally, the left atrial passive and active emptying volumes increased (p < 0.001), while the reservoir and pump (active emptying) functions decreased (with p-values of 0.03 and 0.01, respectively). The passive emptying function, however, showed no significant change (p = 0.65). Decreases in LVEF were observed, while LVEDD, LVESD, IVS, PW, and LA diameters increased (p-value of 0.02 for IVS and <0.001 for the others). Conclusions: Significant impairment of atrial mechanical functions and electromechanical parameters was observed after treatment with cardiotoxic chemotherapeutic agents. This suggests an elevated likelihood of atrial arrhythmia linked to the use of cardiotoxic chemotherapeutic agents. [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]

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: 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]

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]

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]

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]

Simple Summary: This systematic review of the medical literature concerning the overlap between adnexal and gastrointestinal stromal tumors (GISTs) was designed to provide the overall number of previous observed cases and to calculate outcome prognosis, specifically the disease-free survival and overall survival. The impact of immunostaining and new chemotherapeutic medication such as Imatinib are also discussed. Background: Gastrointestinal stromal tumors (GISTs) are a rare neoplasm, sometimes mimicking primary ovarian tumors (OTs) and/or metastasizing to the ovaries (M-OT). We performed a systematic literature review (SLR) of OTs and M-OTs, investigating differences in recurrence-free and overall survival. Methods: Our SLR was performed according to PRISMA guidelines, searching in Pubmed, Scopus, and Web of Science databases from inception until 21 April 2024. Results: Overall, 59 OTs (Group 1) and 21 M-OTs (Group 2) were retrieved. The absence of residual disease after surgery was achieved significantly in a higher percentage of patients with Group 1 GISTs (91.5%) compared with Group 2 GISTs (57.1%). Chemotherapy was more frequently administered to Group 2 patients (33% vs. 0%). Recurrence and deaths for disease were significantly more frequent in Group 2 than Group 1 cases (54.5% vs. 6.8%, and 37.5% vs. 9.8%, respectively). Conclusions: GISTs can rarely mimic primary ovarian cancers or even more rarely metastasize to the ovaries. Group 1 GISTs occurred in younger women, were not associated with elevated tumor markers, and had a better prognosis. In contrast, Group 2 GISTs occurred in older women, may exhibit elevated tumor markers, and presented a worse prognosis. However, no significant statistical difference for survival between the two studied groups was detected. Computed tomography scans can define the size of GISTs, which correlate to stage and prognostic risk classes. The gold standard treatment is complete surgical resection, which was achieved in almost all cases of Group 1 GISTs and in half of Group 2. Histopathology and immunohistochemistry are essential for the final diagnosis and guide chemotherapy treatment. [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]

Thrombotic microangiopathy (TMA) is an anatomopathological lesion mediated by endothelial dysfunction and characterized by the creation of microthrombi in small vessels. In patients with cancer, it may be due to toxicity secondary to chemotherapy, tumor embolization, or hematopoietic progenitor transplantation. Cancer-associated TMA is an underestimated entity that generally appears in the final stages of the disease, although it may also be the initial manifestation of an underlying cancer. Support treatment is necessary in all cases and, depending on the cause, different targeted therapies may be used. The prognosis is very poor. In this article we present a comprehensive review of the existing literature on the physiological mechanisms of cancer-associated TMA. Afterwards, five clinical cases will be presented of patients who developed TMA and were diagnosed in our Department in 2023. We present a discussion of the different causes that triggered the condition, the possible reasons behind the underestimation of this pathology, and the measures that may be adopted. [ABSTRACT FROM AUTHOR]