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Simple Summary: Patients with breast cancer frequently complaint from insomnia difficulties that can affect quality of life and cancer progression. Such difficulties may result from rest-activity (i.e., 24 h alternation of sleep and wake) rhythm alterations consistently reported in this pathology. Currently proposed approaches to counter insomnia difficulties in patients with breast cancer have positive effects only on sleep complaints and well-being. Moreover, such approaches may be difficult to implement shortly after chemotherapy. Innovatively, vestibular stimulation would be particularly suited to tackling insomnia symptoms in patients with breast cancer. Indeed, recent reports have shown that vestibular stimulation could improve rest-activity rhythm and sleep in healthy volunteers. This perspective paper aims to support the evidence of using vestibular stimulation to improve rest-activity rhythms and reduce insomnia symptoms in patients with BC, with beneficial effects on quality of life and, potentially, survival. Insomnia symptoms are common among patients with breast cancer (BC; 20–70%) and are predictors of cancer progression and quality of life. Studies have highlighted sleep structure modifications, including increased awakenings and reduced sleep efficiency and total sleep time. Such modifications may result from circadian rhythm alterations consistently reported in this pathology and known as carcinogenic factors, including lower melatonin levels, a flattened diurnal cortisol pattern, and lower rest-activity rhythm amplitude and robustness. Cognitive behavioral therapy and physical activity are the most commonly used non-pharmacological interventions to counter insomnia difficulties in patients with BC. However, their effects on sleep structure remain unclear. Moreover, such approaches may be difficult to implement shortly after chemotherapy. Innovatively, vestibular stimulation would be particularly suited to tackling insomnia symptoms. Indeed, recent reports have shown that vestibular stimulation could resynchronize circadian rhythms and improve deep sleep in healthy volunteers. Moreover, vestibular dysfunction has been reported following chemotherapy. This perspective paper aims to support the evidence of using galvanic vestibular stimulation to resynchronize circadian rhythms and reduce insomnia symptoms in patients with BC, with beneficial effects on quality of life and, potentially, survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Canine lymphoma is a common cancer of one of the white blood cells that is commonly treated with chemotherapy. Many papers have been published about this disease and treatment, but few comprehensive reviews of the outcomes reported after chemotherapy, and the prognostic factors that influence the outcomes, have been published. Knowledge of the potential outcomes for this disease is important for veterinarians as they guide dog owners in the decision making about treatment options. This review evaluated the papers published on this topic and found that there is a wide variation in outcomes reported, as well as the factors that influence the outlook. Additionally, while individual papers have shown a much better survival, over the last 40 years, the overall improvement in outcome has been modest at best. The use of uniform reporting in the studies is needed, and novel approaches are likely needed to significantly improve the outlook for dogs with this disease. While canine lymphoma is a relatively common and important disease seen by veterinarians, there are limited comprehensive reviews of the literature regarding the remission and survival times following chemotherapy, and the associated prognostic factors. This comprehensive thematic review covers the available veterinary literature covering treatment outcomes and identified prognostic factors. A lack of standardised approaches to evaluate and report the outcomes was identified, including factors that would alter the duration of responses by weeks, or occasionally months. After publication of the suggested reporting criteria, this has improved but is still not uniformly applied. The prognostic factors included for evaluation varied from as few as three to seventeen, with over 50 studies using only univariate analysis. Individual papers reported much longer outcomes than others, but assessing the outcomes overall, there has been minimal change over the last 40 years. This supports the belief that novel approaches for lymphoma therapy will be required to substantively improve outcomes. [ABSTRACT FROM AUTHOR]

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]

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]

Simple Summary: The updated results of the RMS2005 randomized study confirm that patients with non-metastatic high risk rhabdomyosarcoma have an improved survival when maintenance chemotherapy (MC) with vinorelbine and low dose cyclophosphamide is added to the standard multidisciplinary treatment. A more recent randomized study adopted the same strategy, but different drugs were used in the MC phase (trofosfamide, idarubicin and etoposide). No survival improvement was evident in the MC group, suggesting that not all types of MC are equally effective. A revision of the literature demonstrates that the role of MC in patients with metastatic or relapsed RMS may be a promising approach but need more investigations. Maintenance chemotherapy (MC) defines the administration of prolonged relatively low-intensity chemotherapy with the aim of "maintaining" tumor complete remission. This paper aims to report an update of the RMS2005 trial, which demonstrated better survival for patients with high-risk localized rhabdomyosarcoma (RMS) when MC with vinorelbine and low-dose cyclophosphamide was added to standard chemotherapy, and to discuss the published experience on MC in RMS. In the RMS2005 study, the outcome for patients receiving MC vs. those who stopped the treatment remains superior, with a 5-year disease-free survival of 78.1% vs. 70.1% (p = 0.056) and overall survival of 85.0% vs. 72.4% (p = 0.008), respectively. We found seven papers describing MC in RMS, but only one randomized trial that did not demonstrate any advantage when MC with eight courses of trofosfamide/idarubicine alternating with trofosfamide/etoposide has been employed in high-risk RMS. The use of MC showed better results in comparison to high-dose chemotherapy in non-randomized studies, including metastatic patients, and demonstrated feasibility and tolerability in relapsed RMS. Many aspects of MC in RMS need to be investigated, including the best drug combination and the optimal duration. The ongoing EpSSG trial will try to answer some of these questions. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancers (NSCLCs) can be treated with chemotherapy, radiotherapy, immunotherapy, or a combination before undergoing surgical resection. However, uncertainty remains regarding the overall outcomes of patients undergoing minimally invasive surgical (MIS) resection of the lung, following systemic treatment. As such, we studied the existing data on outcomes of this patient population via a comprehensive dive into the literature and performed a meta-analysis. Our findings indicate that MIS can be safely performed following systemic treatment in patients with NSCLC. Notably, MIS resection offers added benefits including significantly higher lymph node yield compared to open surgery. We also address the various complication rates of both open and MIS surgical approaches, underscoring the importance of surgeon preparedness to convert MIS approaches to open surgeries in precarious circumstances. Overall, this study provides valuable insights into the safety and efficacy of MIS resection post-systemic treatment for patients with NSCLC, offering potential improvements in patient outcomes and guidance to surgical decision making. Background: Minimally invasive surgeries for non-small cell lung cancers (NSCLCs) such as video-assisted thoracoscopic surgeries (VATSs) and robotic-assisted thoracoscopic surgeries (RATSs) have become standard of care for patients needing surgical resection in early stages. The role for neoadjuvant systemic therapy has increased with patients receiving neoadjuvant systemic chemotherapy and immunotherapy. However, there has been some equipoise over the intraoperative and overall outcomes for these patients. Here, we review the current data regarding outcomes of patients undergoing minimally invasive thoracic surgical resection after systemic chemotherapy, immunotherapy, or both. Methods: A systematic literature review of randomized controlled trials and observational studies presenting data on patients with NSCLC that underwent neoadjuvant systemic therapy followed by minimally invasive surgery was performed assessing complications, conversion rates, and lymph node yield. Results: Our search strategy and review of references resulted in 239 publications to screen with 88 full texts assessed and 21 studies included in our final review. VATS had a statistically significant higher lymph node yield in five studies. The reported conversion rates ranged from 0 to 54%. Dense adhesions, bleeding, and difficult anatomy were the most common reported reasons for conversion to open surgeries. The most common complications between both groups were prolonged air leak, arrhythmia, and pneumonia. VATS was found to have significantly fewer complications in three papers. Conclusions: The current literature supports VATS as safe and feasible for patients with NSCLC after neoadjuvant systemic treatment. Surgeons should remain prepared to convert to open surgeries in those patients with dense adhesions and bleeding risk. [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: Hyperthermic intraperitoneal chemotherapy (HIPEC) is used to target microscopic peritoneal disease which can remain after visible disease has been surgically removed. It is used in the management of multiple adult cancer types, yet its use in the pediatric population is limited. This review paper provides an overview of the use of this modality in pediatrics in order to identify chemotherapy choice, document reported post-operative morbidity and mortality, and evaluate impact on overall survival. The use of HIPEC, most commonly with cisplatin, is generally tolerable with short-term post-operative complications and no reported post-operative mortality, yet the impact on overall survival versus systemic chemotherapy and debulking surgery is uncertain due to lack of clinical trials and small sample size. Continued gathering of outcome data of pediatric patients treated with HIPEC will aid the rational and safe application of HIPEC to pediatric peritoneal malignancies. Hyperthermic intraperitoneal chemotherapy (HIPEC) can directly target microscopic peritoneal disease, has achieved regular consideration in the treatment of several adult cancer types, and is more recently being studied in pediatrics. This review paper provides an overview of the use of this modality in pediatrics in order to identify medication choice, discuss post-operative morbidity and mortality, and evaluate impact on overall survival. Four databases were searched including Scopus, PubMed, Embase, and CINAHL and ultimately 37 papers documenting the use of this modality comprising 264 pediatric patients were included. Malignancies treated include desmoplastic small round cell tumor, rhabdomyosarcoma, angiosarcoma, colorectal carcinoma, and mesothelioma, with several rarer tumor types. Cisplatin was the most commonly used drug for HIPEC at varying concentrations for 30–90 min in duration at temperatures of approximately 41–42 °C. Reported toxicities were generally self-limited and there was no post-operative mortality. The impact on overall survival versus systemic chemotherapy and debulking surgery is uncertain due to lack of clinical trials and very small sample size across tumor subsets and the overall pediatric population. The relationship between degree of tumor burden and extent of surgical debulking needs to be further clarified. Future directions include prospective clinical trials, establishment of patient databases to facilitate standardization of HIPEC in pediatric patients, and additional approaches to optimize HIPEC. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a feasible method of intraperitoneal drug administration in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method of low-dose chemotherapy as a pressurized aerosol in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. Methods: A systematic literature search was performed using Medline and Web of Science databases from 1 January 2011, to inception, to 31 December 2021. Data were independently extracted by two authors. The Newcastle-Ottawa Scale was used to assess the quality and risk of bias of studies. Meta-analysis was performed for pathological response, radiological response, PCI variation along treatment, and for patients undergoing three or more PIPAC. Pooled analyses were performed using the Freeman–Tukey double arcsine transformation, and 95% CIs were calculated using Clopper–Pearson exact CIs in all instances. Results: A total of 414 papers on PIPAC were identified, and 53 studies considering 4719 PIPAC procedure in 1990 patients were included for analysis. The non-access rate or inability to perform PIPAC pooled rate was 4% of the procedures performed. The overall proportion of patients who completed 3 or more cycles of PIPAC was 39%. Severe toxicities considering CTCAE 3–4 were 4% (0% to 38.5%). In total, 50 studies evaluated deaths within the first 30 postoperative days. In the included 1936 patients were registered 26 deaths (1.3%). The pooled analysis of all the studies reporting a pathological response was 68% (95% CI 0.61–0.73), with an acceptable heterogeneity (I2 28.41%, p = 0.09). In total, 10 papers reported data regarding the radiological response, with high heterogeneity and a weighted means of 15% (0% to 77.8%). PCI variation along PIPAC cycles were reported in 14 studies. PCI diminished, increased, or remained stable in eight, one and five studies, respectively, with high heterogeneity at pooled analysis. Regarding survival, there was high heterogeneity. The 12-month estimated survival from first PIPAC for colorectal cancer, gastric cancer, gynecological cancer and hepatobiliary/pancreatic cancer were, respectively, 53%, 25%, 59% and 37%. Conclusions: PIPAC may be a useful treatment option for selected patients with PM, with acceptable grade 3 and 4 toxicity and promising survival benefit. Meta-analysis showed high heterogeneity of data among up-to-date available studies. In a subset analysis per primary tumor origin, pathological tumor regression was documented in 68% of the studies with acceptable heterogeneity. Pathological regression seems, therefore, a reliable outcome for PIPAC activity and a potential surrogate endpoint of treatment response. We recommend uniform selection criteria for patients entering a PIPAC program and highlight the urgent need to standardize items for PIPAC reports and datasets. [ABSTRACT FROM AUTHOR]

The application of chemotherapy drugs in tumor treatment has a long history, but the lack of selectivity of drugs often leads to serious side effects during chemotherapy. The natural anti-tumor ingredients derived from Chinese herbal medicine are attracting increased attention due to their diverse anti-tumor effects, abundant resources, and minimal side effects. An effective anti-tumor strategy may lie in the combination of these naturally derived anti-tumor ingredients with conventional chemotherapy drugs. This approach could potentially inhibit tumor growth and the development of drug resistance in tumor cells while reducing the adverse effects of chemotherapy drugs. This review provides a comprehensive overview of the combined therapy strategies integrating natural anti-tumor components from Chinese herbal medicine with chemotherapy drugs in current research. We primarily summarize various compounds in Chinese herbal medicine exhibiting natural anti-tumor activities and the relevant mechanisms in synergistic anti-tumor combination therapy. The focus of this paper is on underlining that this integrative approach, combining natural anti-tumor components of Chinese herbal medicine with chemotherapy drugs, presents a novel cancer treatment methodology, thereby providing new insights for future oncological research. [ABSTRACT FROM AUTHOR]

Simple Summary: As a first-line chemotherapeutic for colorectal cancer (CRC), FOLFOX, XELOX, and similar regimens are recommended as adjuvant therapies following CRC surgery, according to the NCCN guidelines. In stage IV patients, targeted therapies like cetuximab and bevacizumab are used in combination. The decision to add either irinotecan-based regimens or oxaliplatin-based regimens, FOLFIRI is typically based on a physician's subjective judgment due to the lack of clear selection criteria. Therefore, having the ability to precisely predict the therapeutic response to these two drugs could help prioritize the use of the most effective drug in stage IV patients. Previous research efforts aimed to predict therapeutic responses to these two drugs using organoids. While irinotecan showed promising predictability, predicting the response to oxaliplatin remained challenging. In this study, new drug screening conditions were identified to address this issue. Through additional research using CRC organoids, this paper contributes to the prediction of drug responses in CRC patients. Colorectal cancer is the third most common cancer in the world, with an annual incidence of 2 million cases. The success of first-line chemotherapy plays a crucial role in determining the disease outcome. Therefore, there is an increasing demand for precision medicine to predict drug responses and optimize chemotherapy in order to increase patient survival and reduce the related side effects. Patient-derived organoids have become a popular in vitro screening model for drug-response prediction for precision medicine. However, there is no established correlation between oxaliplatin and drug-response prediction. Here, we suggest that organoid culture conditions can increase resistance to oxaliplatin during drug screening, and we developed a modified medium condition to address this issue. Notably, while previous studies have shown that survivin is a mechanism for drug resistance, our study observed consistent survivin expression irrespective of the culture conditions and oxaliplatin treatment. However, clusterin induced apoptosis inhibition and cell survival, demonstrating a significant correlation with drug resistance. This study's findings are expected to contribute to increasing the accuracy of drug-response prediction in patient-derived APC mutant colorectal cancer organoids, thereby providing reliable precision medicine and improving patient survival rates. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the multidrug nature of anticancer treatment, attempts are still being made to determine the relationship between the duration of chemotherapy, the dose of individual drugs, and the occurrence of dental developmental abnormalities. There are relatively few papers devoted to this issue, and all of them are based on the study groups composed of individuals receiving various treatment regimens. The current study includes a group of acute lymphoblastic leukemia survivors who underwent chemotherapy according to the ALL IC-BFM 2002 protocol. Contrary to the observations of some authors, the results of the current research suggest that the age at the start of chemotherapy is likely to be the strongest risk factor for toxic injury during tooth development. A small study cohort is a major limitation, but an evaluation of similar relationships at larger research centers would be helpful in better understanding the problem. The multidrug nature of anticancer treatment and different treatment protocols used in the studies are likely to be a major limitation in establishing real risk factors determining the occurrence of dental abnormalities. The authors aimed to establish a relationship between the duration and the dose of chemotherapy and the number of tooth adverse effects in the group receiving the same treatment. Of the 40 anticancer therapy recipients who attended the outpatient dental clinic, 7 leukemia survivors receiving the treatment according to the ALL IC-BFM 2002 protocol were selected. The study group consisted of four females and three males aged 92 to 207 months at the time of dental examination and 29 to 91 months at leukemia diagnosis. As a result of the clinical and radiological examination, dental abnormalities such as agenesis, tooth size reduction, root abnormalities, and taurodontia were identified, and the medical records of all survivors were reviewed in terms of drugs administered, their doses, and treatment schedules. No correlation was observed between the treatment duration of an intensive therapy, the entire therapy, and the number of tooth abnormalities. No relationship was also found between the number of dental abnormalities and the cumulative dose of vincristine, L-asparaginase, methotrexate, cyclophosphamide, cytarabine, and 6-mercaptopurine. The age at the onset of antineoplastic therapy is likely to be the strongest risk factor for toxic injury during tooth development. [ABSTRACT FROM AUTHOR]

Simple Summary: The tumor microenvironment (TME) is defined as the environment surrounding a tumor. There is a close, dynamic relation and interaction between the tumor and its neighboring microenvironment. There are some particularities of the thymus itself and of the TME of thymic epithelial tumors that hinder the routine use of targeted therapies, including immune checkpoint inhibitors. The understanding of the unique characteristics of the TME of thymic epithelial tumors could possibly result in the development of novel promising therapies. The tumor microenvironment (TME) is a complex and constantly changing entity. The TME consists of stromal cells, fibroblasts, endothelial cells, and innate and adaptive immune cells. Cancer development and progression occurs through this interplay between the tumor and the adjacent stroma. Cancer cells are capable of modifying their microenvironment by secreting various message-carrying molecules, such as cytokines, chemokines, and other factors. This action causes a reprogramming of the neighboring cells, which are enabled to play a crucial role in tumor survival and progression. The study of TME has many clinical implications in terms of cancer therapeutics because many new drugs, such as antibodies, kinase inhibitors, and liposome formulations that can encapsulate anti-cancer drugs, can be developed. Although chemotherapy is considered the standard of treatment for advanced disease, recent research has brought to light immunotherapy as a possible systemic alternative. However, the complex structure and function of the thymus hinders its routine use in clinical practice. The aim of this review paper is to discuss the recent advances in the investigation of the unique characteristics of the TME of thymic epithelial tumors that could possibly lead to the development of novel promising therapies. [ABSTRACT FROM AUTHOR]

Incorporating scientific research into clinical practice via clinical informatics, which includes genomics, proteomics, bioinformatics, and biostatistics, improves patients' treatment. Computational pathology is a growing subspecialty with the potential to integrate whole slide images, multi-omics data, and health informatics. Pathology and laboratory medicine are critical to diagnosing cancer. This work will review existing computational and digital pathology methods for breast cancer diagnosis with a special focus on deep learning. The paper starts by reviewing public datasets related to breast cancer diagnosis. Additionally, existing deep learning methods for breast cancer diagnosis are reviewed. The publicly available code repositories are introduced as well. The paper is closed by highlighting challenges and future works for deep learning-based diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Adrenocortical cancer (ACC) is a rare malignancy with a poor prognosis and few treatment options. Surgery is the only curative option, but many patients present after the disease has become metastatic or recurs after surgery. There have been few advances in treatment since mitotane's discovery in the 1960s, and it remains the only FDA-approved ACC treatment. This paper reviews the current treatment approaches, what we have recently learned about the disease, and the next steps needed to advance research and improve therapeutic options for this disease. Adrenocortical cancer (ACC) typically presents in advanced stages of disease and has a dismal prognosis. One of the foremost reasons for this is the lack of available systemic therapies, with mitotane remaining the backbone of treatment since its discovery in the 1960s, despite underwhelming efficacy. Surgery remains the only potentially curative option, but about half of patients will recur post-operatively, often with metastatic disease. Other local treatment options have been attempted but are only used practically on a case-by-case basis. Over the past few decades there have been significant advances in understanding the molecular background of ACC, but this has not yet translated to better treatment options. Attempts at novel treatment strategies have not provided significant clinical benefit. This paper reviews our current treatment options and molecular understanding of ACC and the reasons why a successful treatment has remained elusive. Additionally, we discuss the knowledge gaps that need to be overcome to bring us closer to successful treatment and ways to bridge them. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is basically a tough condition on a patient's body where cell grows uncontrollably. Normal cells are affected, which destroys the health of the patient. The main problem in cancer is spreading from one part to another. Therefore, the mathematical modeling of cancerous tumors integrates to check overall stability. A novel approach is introduced such as Bernstein polynomial with combination of genetic algorithm, sliding mode controller, and synergetic control. The proposed solution has easily eliminated cancerous cells within five days using synergetic control. In addition, five cases are incorporated to evaluate error function. In addition, a brief comparative study is added to contrast the simulation results with theoretical modeling. Cancerous tumor cells divide uncontrollably, which results in either tumor or harm to the immune system of the body. Due to the destructive effects of chemotherapy, optimal medications are needed. Therefore, possible treatment methods should be controlled to maintain the constant/continuous dose for affecting the spreading of cancerous tumor cells. Rapid growth of cells is classified into primary and secondary types. In giving a proper response, the immune system plays an important role. This is considered a natural process while fighting against tumors. In recent days, achieving a better method to treat tumors is the prime focus of researchers. Mathematical modeling of tumors uses combined immune, vaccine, and chemotherapies to check performance stability. In this research paper, mathematical modeling is utilized with reference to cancerous tumor growth, the immune system, and normal cells, which are directly affected by the process of chemotherapy. This paper presents novel techniques, which include Bernstein polynomial (BSP) with genetic algorithm (GA), sliding mode controller (SMC), and synergetic control (SC), for giving a possible solution to the cancerous tumor cells (CCs) model. Through GA, random population is generated to evaluate fitness. SMC is used for the continuous exponential dose of chemotherapy to reduce CCs in about forty-five days. In addition, error function consists of five cases that include normal cells (NCs), immune cells (ICs), CCs, and chemotherapy. Furthermore, the drug control process is explained in all the cases. In simulation results, utilizing SC has completely eliminated CCs in nearly five days. The proposed approach reduces CCs as early as possible. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of our study is to provide a wide perspective on the available literature data on the immune landscape of breast cancers, focusing on TILs and PD-L1 expression across different breast cancer subtypes. Moreover, treatment options such as immunotherapy and chemotherapy in adjuvant and neoadjuvant settings are discussed, along with the most relevant cut-offs and scores for TILs and PD-L1 pathological assessment. With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature concerning the immunogenicity of breast cancer has been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune response in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ subtypes, where increased TIL levels have been linked to a better response to neoadjuvant chemotherapy and improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes, and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes. Briefly, TNBC shows the highest percentage of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0–10% of cases) in hormone-receptor-positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points, and scoring systems have been utilized across published studies. In the present paper, an extensive review of the current knowledge of the immune landscape of BC is provided. TILS and PD-L1 expression across different BC subtypes are discussed, providing a guide for their pathological assessment and reporting. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is the most common malignant brain tumor associated with a poor prognosis, with a median survival of 14 months. Despite initial treatment with surgery, radiotherapy, and chemotherapy, recurrence is the usual situation. Controversy remains over the best treatment strategy for recurrent disease, and there is no standard of treatment in this situation. Different forms of treatment have been addressed, including a surgical procedure or radiotherapy, systemic treatment with chemotherapy or targeted drugs, and different immunotherapy strategies. Knowledge of the data from these studies allows for improved decision-making in this clinical situation. Glioblastoma is a disease with a poor prognosis. Multiple efforts have been made to improve the long-term outcome, but the 5-year survival rate is still 5–10%. Recurrence of the disease is the usual way of progression. In this situation, there is no standard treatment. Different treatment options can be considered. Among them would be reoperation or reirradiation. There are different studies that have assessed the impact on survival and the selection of patients who may benefit most from these strategies. Chemotherapy treatments have also been considered in several studies, mainly with alkylating agents, with data mostly from phase II studies. On the other hand, multiple studies have been carried out with target-directed treatments. Bevacizumab, a monoclonal antibody with anti-angiogenic activity, has demonstrated activity in several studies, and the FDA has approved it for this indication. Several other TKI drugs have been evaluated in this setting, but no clear benefit has been demonstrated. Immunotherapy treatments have been shown to be effective in other types of tumors, and several studies have evaluated their efficacy in this disease, both immune checkpoint inhibitors, oncolytic viruses, and vaccines. This paper reviews data from different studies that have evaluated the efficacy of different forms of relapsed glioblastoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, responsible for the majority of cases and ranking seventh as a leading cause of cancer-related deaths. It is difficult to treat because is it often detected at advanced stages, there are no effective screening tests available, and patients can develop resistance to standard treatments like chemotherapy and radiation. Recent interest has involved immunotherapy, which stimulate the immune system to recognise and attack cancer cells. Therefore, our paper aims to summarise the findings of studies investigating immunotherapies in PDAC and we discuss the limitations of such therapies and avenues of future research. In a bid to address the outcomes associated with the disease. Pancreatic ductal adenocarcinoma (PDAC) accounts for up to 95% of all pancreatic cancer cases and is the seventh-leading cause of cancer death. Poor prognosis is a result of late presentation, a lack of screening tests and the fact some patients develop resistance to chemotherapy and radiotherapy. Novel therapies like immunotherapeutics have been of recent interest in pancreatic cancer. However, this field remains in its infancy with much to unravel. Immunotherapy and other targeted therapies have yet to yield significant progress in treating PDAC, primarily due to our limited understanding of the disease immune mechanisms and its intricate interactions with the tumour microenvironment (TME). In this review we provide an overview of current novel immunotherapies which have been studied in the field of pancreatic cancer. We discuss their mechanisms, evidence available in pancreatic cancer as well as the limitations of such therapies. We showcase the potential role of combining novel therapies in PDAC, postulate their potential clinical implications and the hurdles associated with their use in PDAC. Therapies discussed with include programmed death checkpoint inhibitors, Cytotoxic T-lymphocyte-associated protein 4, Chimeric Antigen Receptor-T cell therapy, oncolytic viral therapy and vaccine therapies including KRAS vaccines, Telomerase vaccines, Gastrin Vaccines, Survivin-targeting vaccines, Heat-shock protein (HSP) peptide complex-based vaccines, MUC-1 targeting vaccines, Listeria based vaccines and Dendritic cell-based vaccines. [ABSTRACT FROM AUTHOR]

Simple Summary: Chemotherapy is one of the common methods for the treatment of malignant tumors of the biliary pancreatic system, but chemoresistance reduces treatment effectiveness. In recent years, studies have found that intestinal flora imbalance is closely related to chemotherapy resistance. Targeted regulation of intestinal flora can improve chemotherapy resistance. The purpose of this review is to explore the role of intestinal flora in the chemoresistance of malignant tumors of the biliary pancreatic system and to target the regulation of intestinal flora with antibiotics and probiotics so as to seek potential treatment directions. Biliary pancreatic malignancy has an occultic onset, a high degree of malignancy, and a poor prognosis. Most clinical patients miss the opportunity for surgical resection of the tumor. Systemic chemotherapy is still one of the important methods for the treatment of biliary pancreatic malignancies. Many chemotherapy regimens are available, but their efficacy is not satisfactory, and the occurrence of chemotherapy resistance is a major reason leading to poor prognosis. With the advancement of studies on intestinal flora, it has been found that intestinal flora is correlated with and plays an important role in chemotherapy resistance. The application of probiotics and other ways to regulate intestinal flora can improve this problem. This paper aims to review and analyze the research progress of intestinal flora in the chemotherapy resistance of biliary pancreatic malignancies to provide new ideas for treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: We present eight core attributes of cancer growth that we must address for a more effective treatment than we currently have. To do this we outline why a regimen simultaneously using many different drugs will be needed. At our current state of knowledge, even adding two or three drugs will not counter all the growth attributes of a currently incurable cancer. We show in this paper, the details of how an example six drug regimen, when added alongside of current traditional treatments, might inhibit enough of the eight core growth driving elements to allow those standard treatments to be more effective. We further show how medicines from general medical practice used to treat pain, fungal infections, psychosis, leprosy and other non-cancer related illnesses can be repurposed to block cancer cells' survival pathways and growth drives. In part one of this two-part paper, we present eight principles that we believe must be considered for more effective treatment of the currently incurable cancers. These are addressed by multidrug adjunctive cancer treatment (MDACT), which uses multiple repurposed non-oncology drugs, not primarily to kill malignant cells, but rather to reduce the malignant cells' growth drives. Previous multidrug regimens have used MDACT principles, e.g., the CUSP9v3 glioblastoma treatment. MDACT is an amalgam of (1) the principle that to be effective in stopping a chain of events leading to an undesired outcome, one must break more than one link; (2) the principle of Palmer et al. of achieving fractional cancer cell killing via multiple drugs with independent mechanisms of action; (3) the principle of shaping versus decisive operations, both being required for successful cancer treatment; (4) an idea adapted from Chow et al., of using multiple cytotoxic medicines at low doses; (5) the idea behind CUSP9v3, using many non-oncology CNS-penetrant drugs from general medical practice, repurposed to block tumor survival paths; (6) the concept from chess that every move creates weaknesses and strengths; (7) the principle of mass—by adding force to a given effort, the chances of achieving the goal increase; and (8) the principle of blocking parallel signaling pathways. Part two gives an example MDACT regimen, gMDACT, which uses six repurposed drugs—celecoxib, dapsone, disulfiram, itraconazole, pyrimethamine, and telmisartan—to interfere with growth-driving elements common to cholangiocarcinoma, colon adenocarcinoma, glioblastoma, and non-small-cell lung cancer. gMDACT is another example of—not a replacement for—previous multidrug regimens already in clinical use, such as CUSP9v3. MDACT regimens are designed as adjuvants to be used with cytotoxic drugs. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a group of tumors with different clinical manifestations, various localizations in the human body, and a particularly wide range of histological types, grades and severities. Their diagnosis and therapeutic management are complex. Current standards are not always effective, and sometimes require modifications. Thus, knowledge about GEP-NENs and approaches for the treatment of these patients in Europe and all over the world are constantly evolving. The aim of this review is to highlight the progress in diagnostics and treatment of GEP-NENs. Special attention is given to GEP-NETs as the most widely reported in the literature. Neuroendocrine neoplasms (NENs) are an increasingly common cause of neoplastic diseases. One of the largest groups of NENs are neoplasms localized to the gastroenteropancreatic system, which are known as gastroenteropancreatic NENs (GEP-NENs). Because of nonspecific clinical symptoms, GEP-NEN patient diagnosis and, consequently, their treatment, might be difficult and delayed. This situation has forced researchers all over the world to continue progress in the diagnosis and treatment of patients with GEP-NENs. Our review is designed to present the latest reports on the laboratory diagnostic techniques, imaging tests and surgical and nonsurgical treatment strategies used for patients with these rare neoplasms. We paid particular attention to the nuclear approach, the use of which has been applied to GEP-NEN patient diagnosis, and to nonsurgical and radionuclide treatment strategies. Recent publications were reviewed in search of reports on new strategies for effective disease management. Attention was also paid to those studies still in progress, but with successful results. A total of 248 papers were analyzed, from which 141 papers most relevant to the aim of the study were selected. Using these papers, we highlight the progress in the development of diagnostic and treatment strategies for patients with GEP-NENs. [ABSTRACT FROM AUTHOR]

To prevent local tumor recurrence caused by possible residual cancer cells after surgery, avoid toxicity of systemic chemotherapy and protect the fragile immune system of postsurgical patients, an increasing amount of attention has been paid to local anti–cancer drug delivery systems. In this paper, golden buckwheat was first applied to prevent post–operative tumor recurrence, which is a Chinese herb and possesses anti–tumor activity. Golden buckwheat extract–loaded gellan gum injectable hydrogels were fabricated via Ca2+ crosslinking for localized chemotherapy. Blank and/or drug–loaded hydrogels were characterized via FT–IR, TG, SEM, density functional theory, drug release and rheology studies to explore the interaction among gellan gum, Ca2+ and golden buckwheat extract (GBE). Blank hydrogels were non–toxic to NIH3T3 cells. Of significance, GBE and GBE–loaded hydrogel inhibited the proliferation of tumor cells (up to 90% inhibition rate in HepG2 cells). In vitro hemolysis assay showed that blank hydrogel and GBE–loaded hydrogel had good blood compatibility. When GBE–loaded hydrogel was applied to the incompletely resected tumor of mice bearing B16 tumor xenografts, it showed inhibition of tumor growth in vivo and induced the apoptosis of tumor cells. Taken together, gellan gum injectable hydrogel containing GBE is a potential local anticancer drug delivery system for the prevention of postsurgical tumor recurrence. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy has relevant implications for cancer patients' physical, social, and psychological health. Foot health has gained relevance in recent years due to its importance to independence and wellbeing, especially in chronic conditions. This study aims to explore the scope of the literature regarding foot health problems in people with cancer undergoing chemotherapy. Methods: scoping review following the PRISMA-ScR, Arksey and O'Malley, and the Joanna Briggs Institute guidelines. Different databases were used (Cochrane Plus, Scopus, Web of Science, and Pubmed). A total of 4911 articles were identified. Finally, 11 papers were included. Results: Foot problems are relevant and deteriorate wellbeing. The prevalence of some podiatric pathologies is controversial. The main literature deals with hand–foot syndrome and peripheral neuropathy. Focused instruments on foot health were not thoroughly used. Conclusion: There is insufficient evidence on foot health problems and their influence on the quality of life of people with cancer undergoing chemotherapy. Even though a significant percentage of this population has a foot problem, its care and importance are neglected. More studies are needed to contribute to the care of people with cancer through foot health. [ABSTRACT FROM AUTHOR]

Relapsed and/or refractory (R/R) acute myeloid leukemia (AML) is hallmarked by dramatic prognosis. Treatment remains challenging, with allogeneic hematopoietic stem cell transplantation (HSCT) as the only curative option. The BCL-2 inhibitor venetoclax (VEN) has proven to be a promising therapy for AML and is currently the standard of care in combination with hypomethylating agents (HMAs) for newly diagnosed AML patients ineligible for induction chemotherapy. Given its satisfactory safety profile, VEN-based combinations are increasingly being investigated as a part of the therapeutic strategy for R/R AML. The current paper aims to provide a comprehensive review of the main evidence regarding VEN in the setting of R/R AML, with a specific focus on combinational strategies, including HMAs and cytotoxic chemotherapy, as well as different clinical settings, especially in view of the crucial role of HSCT. A discussion of what is known about drug resistance mechanisms and future combinational strategies is also provided. Overall, VEN-based regimes (mainly VEN + HMA) have provided unprecedented salvage treatment opportunities in patients with R/R AML, with low extra-hematological toxicity. On the other hand, the issue of overcoming resistance is one of the most important fields to be addressed in upcoming clinical research. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma multiforme is one of the hardest-to-treat brain tumors, often resistant to conventional treatments such as chemotherapy and radiation therapy. Despite advances in cancer research and treatment, the survival rate for glioblastoma patients remains low, with most patients only surviving for a few months to a year after diagnosis. This is due in part to the nature of glioblastoma tumors, which contain cells that are highly resistant to traditional cancer treatments. These cancer cells can evade the effects of chemotherapy and radiation therapy, making it difficult to achieve lasting remissions or cures. This work aims to summarize recent findings about this tumor and the progress in developing new treatment options. The highest focus of this paper is on the mechanisms of glioblastoma multiforme resistance and the possibility to reverse it using nanocarriers. Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer that is difficult to treat due to its resistance to both radiation and chemotherapy. This resistance is largely due to the unique biology of GBM cells, which can evade the effects of conventional treatments through mechanisms such as increased resistance to cell death and rapid regeneration of cancerous cells. Additionally, the blood–brain barrier makes it difficult for chemotherapy drugs to reach GBM cells, leading to reduced effectiveness. Despite these challenges, there are several treatment options available for GBM. The standard of care for newly diagnosed GBM patients involves surgical resection followed by concurrent chemoradiotherapy and adjuvant chemotherapy. Emerging treatments include immunotherapy, such as checkpoint inhibitors, and targeted therapies, such as bevacizumab, that attempt to attack specific vulnerabilities in GBM cells. Another promising approach is the use of tumor-treating fields, a type of electric field therapy that has been shown to slow the growth of GBM cells. Clinical trials are ongoing to evaluate the safety and efficacy of these and other innovative treatments for GBM, intending to improve with outcomes for patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer antigen 125 (CA-125) is a protein found at a high concentration in the blood of patients with specific types of cancer, mainly ovarian cancer. In 2004, the Gynecologic Cancer Intergroup (GCIG) proposed criteria defining response to treatment, as well as disease progression, based on the CA-125 concentration. Ever since, for the follow-up of ovarian cancer patients, the CA-125 concentration and/or CT-scans are used. This paper aims to compare different summaries of CA-125 evolution in the 3 to 6 months following treatment initiation in newly diagnosed advanced ovarian cancer and explore their prognostic capacity to predict overall survival. Based on individual patient data from the GCIG meta-analysis, we propose the most appropriate timeframe between follow-up and the prediction horizon in order to obtain robust, dynamic, individual predictions. (1) Background: Cancer antigen 125 (CA-125) is a protein produced by ovarian cancer cells that is used for patients' monitoring. However, the best ways to analyze its decline and prognostic role are poorly quantified. (2) Methods: We leveraged individual patient data from the Gynecologic Cancer Intergroup (GCIG) meta-analysis (N = 5573) to compare different approaches summarizing the early trajectory of CA-125 before the prediction time (called the landmark time) at 3 or 6 months after treatment initiation in order to predict overall survival. These summaries included observed and estimated measures obtained by a linear mixed model (LMM). Their performances were evaluated by 10-fold cross-validation with the Brier score and the area under the ROC (AUC). (3) Results: The estimated value and the last observed value at 3 months were the best measures used to predict overall survival, with an AUC of 0.75 CI 95% [0.70; 0.80] at 24 and 36 months and 0.74 [0.69; 0.80] and 0.75 [0.69; 0.80] at 48 months, respectively, considering that CA-125 over 6 months did not improve the AUC, with 0.74 [0.68; 0.78] at 24 months and 0.71 [0.65; 0.76] at 36 and 48 months. (4) Conclusions: A 3-month surveillance provided reliable individual information on overall survival until 48 months for patients receiving first-line chemotherapy. [ABSTRACT FROM AUTHOR]

While Luria and Delbrück's seminal work has found its way to some college biology textbooks, it is now largely absent from those in mathematics. This is a significant omission, and we consider it a missed opportunity to present a celebrated conceptual model that provides an authentic and, in many ways, intuitive example of the quantifiable nature of stochasticity. We argue that it is an important topic that could enrich the educational literature in mathematics, from the introductory to advanced levels, opening many doors to undergraduate research. The paper has two main parts. First, we present in detail the mathematical theory behind the Luria–Delbrück model and make suggestions for further readings from the literature. We also give ideas for inclusion in various mathematics courses and for projects that can be used in regular courses, independent projects, or as starting points for student research. Second, we briefly review available hands-on activities as pedagogical ways to facilitate problem posing, problem-based learning, and investigative case-based learning and to expose students to experiments leading to Poisson distributions. These help students with even limited mathematics backgrounds understand the significance of Luria–Delbrück's work for determining mutation rates and its impact on many fields, including cancer chemotherapy, antibiotic resistance, radiation, and environmental screening for mutagens and teratogens. [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, the main reason for the ineffectiveness of systemic chemotherapy is the formation of cancer cells with the phenotype of multiple drug resistance (MDR), which are able to survive at high doses of chemotherapy drugs. One of the MDR mechanisms involves the overproduction of proteins of the ABC transporter family, including P-glycoprotein, which are responsible for the transport of a wide range of drugs from the cell. This paper focuses on a new derivative of the natural triterpenoid betulin, oleanane aldehyde-β-enone (OA), having low toxicity toward normal cells and cytotoxicity toward cancer cells and their doxorubicin-resistant variants. The calculations and experimental methods revealed that this compound is not released from cells like most known drugs. The analysis of molecular cellular targets showed that the mechanism of OA toxic action is associated with the activation of the external and/or internal pathways of the apoptotic death of cancer cells and their drug-resistant variants. Thus, OA, as a highly cytotoxic compound toward doxorubicin-resistant cancer cells, can be a promising candidate for drug development. Oleanane aldehyde-β-enone (OA), being the semi-synthetic derivative of the triterpenoid betulin, effectively inhibits the proliferation of HBL-100 and K562 cancer cells (IC50 0.47–0.53 µM), as well as the proliferation of their resistant subclones with high P-gp expression HBL-100/Dox, K562/i-S9 and K562/i-S9_Dox (IC50 0.45−1.24 µM). A molecular docking study, rhodamine efflux test, synergistic test with Dox, and ABC transporter gene expression were used to investigate the ability of OA to act as a P-gp substrate or inhibitor against Dox-resistant cells. We noted a trend toward a decrease in ABCB1, ABCC1 and ABCG2 expression in HBL-100 cells treated with OA. The in silico and in vitro methods suggested that OA is neither a direct inhibitor nor a competitive substrate of P-gp in overexpressing P-gp cancer cells. Thus, OA is able to overcome cellular resistance and can accumulate in Dox-resistant cells to realize toxic effects. The set of experiments suggested that OA toxic action can be attributed to activating intrinsic/extrinsic or only intrinsic apoptosis pathways in Dox-sensitive and Dox-resistant cancer cells, respectively. The cytotoxicity of OA in resistant cells is likely mediated by a mitochondrial cell death pathway, as demonstrated by positive staining with Annexin V–FITC, an increasing number of cells in the subG0/G1 phase, reactive oxygen species generation, mitochondrial dysfunction, cytochrome c migration and caspases-9,-6 activation. [ABSTRACT FROM AUTHOR]

Anal cancer is a rare cancer that accounts for about 2% of all gastrointestinal tract malignancies. Among anal cancer, squamous cell cancer is the most common malignancy. The incidence of all stages of anal squamous cell cancer has been increasing. Human papillomavirus infection and immunosuppression are major risk factors for anal cancer. The management of anal cancer has evolved over the past several decades and continues to do so. Chemoradiation therapy remains the mainstay for treatment for most patients with early-stage disease, whereas systemic therapy is the primary treatment for patients with metastatic disease. Patients with persistent disease or recurrence following chemoradiation therapy are treated with salvage surgery. Access to novel cytotoxic combinations and immunotherapy has improved the outcomes of patients with advanced disease. This review provides an overview of advances in the management of anal cancer over the past two decades. This paper reviews the epidemiology, risk factors, pathology, diagnosis, and management of localized and advanced anal squamous cell cancer, highlights current knowledge gaps in the management of anal cancer, and discusses future directions. [ABSTRACT FROM AUTHOR]

Simple Summary: The importance of identifying and targeting in treating familial breast cancers is becoming increasingly recognized, in particular with increased availability of PARPi-based therapies. This review paper focuses on recognized and emerging prognostic and predictive tumour biomarkers, both recognized and emerging, specifically within familial breast cancer. In particular, these familial breast cancers appear to be different to sporadic lesions, with different interactions and clinical relevance of well-described cancer networks. More so, pre-clinical studies and in vitro models also demonstrate potentially relevant clinical biomarkers, as yet not studied in these groups. Currently, the wider literature has largely focused on prognostic and predictive factors in all breast cancers in general, or biomarkers for genetic susceptibility. This review is novel as there are none currently reviewing biomarkers only within familial breast cancers. Large numbers of breast cancers arise within a familial context, either with known inherited germline mutations largely within DNA repair genes, or with a strong family history of breast and/or ovarian cancer, with unknown genetic underlying mechanisms. These cancers appear to be different to sporadic cases, with earlier age of onset, increased multifocality and with association with specific breast cancer histological and phenotypic subtypes. Furthermore, tumours showing homologous recombination deficiency, due to loss of BRCA1, BRCA2, PALB2 and CHEK2 function, have been shown to be especially sensitive to platinum-based chemotherapeutics and PARP inhibition. While there is extensive research and data accrued on risk stratification and genetic predisposition, there are few data pertaining to relevant prognostic and predictive biomarkers within this breast cancer subgroup. The following is a review of such biomarkers in male and female familial breast cancer, although the data for the former are particularly sparse. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review paper, we focused on the discussion of various important aspects of hormone receptor (HR)-positive breast cancer, including HR structure and signaling, genetics (epigenetics and gene mutations), gene expression-based assays, traditional and new drugs for treatment, and new technological uses in diagnosis and treatment. Particularly, we summarized the commonly mutated genes and abnormally methylated genes in HR-positive breast cancer and compared the common gene expression-based assays that are used in breast cancer as prognostic and/or predictive tools in detail. All of these topic discussions have not been fully described and summarized within other research or review articles. The current molecular classification divides breast cancer into four major subtypes, including luminal A, luminal B, HER2-positive, and basal-like, based on receptor gene expression profiling. Luminal A and luminal B are hormone receptor (HR, estrogen, and/or progesterone receptor)-positive and are the most common subtypes, accounting for around 50–60% and 15–20% of the total breast cancer cases, respectively. The drug treatment for HR-positive breast cancer includes endocrine therapy, HER2-targeted therapy (depending on the HER2 status), and chemotherapy (depending on the risk of recurrence). In this review, in addition to classification, we focused on discussing the important aspects of HR-positive breast cancer, including HR structure and signaling, genetics, including epigenetics and gene mutations, gene expression-based assays, the traditional and new drugs for treatment, and novel or new uses of technology in diagnosis and treatment. Particularly, we have summarized the commonly mutated genes and abnormally methylated genes in HR-positive breast cancer and compared four common gene expression-based assays that are used in breast cancer as prognostic and/or predictive tools in detail, including their clinical use, the factors being evaluated, patient demographics, and the scoring systems. All these topic discussions have not been fully described and summarized within other research or review articles. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we report that the combination of existing therapeutic agents and hemagglutinating virus of Japan envelope (HVJ-E), a virus-inactivating agent, may be a more effective treatment agent for pleural mesothelioma, a refractory cancer for which no effective treatment has been established. We have already reported that HVJ-E, which activates antitumor immunity and induces apoptosis in cancer, can provide a different mechanism for effective treatment. In this report, the antitumor effect of HVJ-E in combination with chemotherapy or immune checkpoint inhibitors (ICIs) activated antitumor immunity in a mouse model of malignant pleural mesothelioma-bearing tumor and significantly enhanced antitumor efficacy compared to single-agent therapy. We report that the use of HVJ-E in combination with chemotherapy or ICIs, which are already used in clinical practice, may be more effective than single-agent therapy. However, further clinical studies are needed before the combination therapy can be used in clinical practice. Malignant pleural mesothelioma (MPM) is a refractory tumor because most of the lesions are already disseminated at diagnosis. Previously, the main treatment for MPM was combination chemotherapy. However, recently, immune checkpoint inhibitors (ICIs) are also used. For better efficacy of MPM treatment, we focused on hemagglutinating virus of Japan envelope (HVJ-E), which activates antitumor immunity and induces tumor-specific cell death. In this paper, we aimed to determine whether HVJ-E as a single agent therapy or in combination with chemotherapy or ICIs is effective in MPM bearing mouse. We confirmed its antitumor efficacy in MPM-bearing mouse. HVJ-E significantly prolonged the survival of human MPM-bearing mouse compared to that of control mouse and when combined with CDDP. This efficacy was lost in NOD-SCID mouse, suggesting that activation of innate immunity by HVJ-E was related to the survival rate. HVJ-E also showed antitumor efficacy in murine MPM-bearing mouse. The combination of chemotherapy and HVJ-E caused a significant increase in cytotoxic T cells (CTLs) compared to chemotherapy alone, suggesting that not only innate immunity activated by HVJ-E but also the increase in CTLs contributed to improved survival. The combination of anti-PD-1 antibody and HVJ-E significantly prolonged the survival rate of murine MPM-bearing mouse. Further, HVJ-E might have exhibited antitumor effects by maintaining immunogenicity against tumors. We believe that HVJ-E may be a beneficial therapy to improve MPM treatment in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is one of the most common malignant tumors in women. Its incidence rate accounts for 7–10% of all kinds of malignant tumors in the whole body, second only to uterine cancer in women, and has become the main cancer threatening women's health. Fortunately, it has been proved that combination therapy of immunotherapy with radiotherapy, targeted technology, and even nanotechnology is active and effective in treating breast cancer, which provides a broader way of studying the treatment of breast cancer. Therefore, the purpose of our review is to study the value of immunotherapy in breast cancer treatment. Moreover, because the treatment of triple-negative breast cancer (TNBC) is difficult, we will discuss this in more detail in this article. Breast cancer (BC) is a representative malignant tumor that affects women across the world, and it is the main cause of cancer-related deaths in women. Although a large number of treatment methods have been developed for BC in recent years, the results are sometimes unsatisfying. In recent years, treatments of BC have been expanded with immunotherapy. In our article, we list some tumor markers related to immunotherapy for BC. Moreover, we introduce the existing relatively mature immunotherapy and the markers' pathogenesis are involved. The combination of immunotherapy and other therapies for BC are introduced in detail, including the combination of immunotherapy and chemotherapy, the combined use of immunosuppressants and chemotherapy drugs, immunotherapy and molecular targeted therapy. We summarize the clinical effects of these methods. In addition, this paper also makes a preliminary exploration of the combination of immunotherapy, radiotherapy, and nanotechnology for BC. [ABSTRACT FROM AUTHOR]

Cancer is a fatal disease with a complex pathophysiology. Lack of specificity and cytotoxicity, as well as the multidrug resistance of traditional cancer chemotherapy, are the most common limitations that often cause treatment failure. Thus, in recent years, significant efforts have concentrated on the development of a modernistic field called nano-oncology, which provides the possibility of using nanoparticles (NPs) with the aim to detect, target, and treat cancer diseases. In comparison with conventional anticancer strategies, NPs provide a targeted approach, preventing undesirable side effects. What is more, nanoparticle-based drug delivery systems have shown good pharmacokinetics and precise targeting, as well as reduced multidrug resistance. It has been documented that, in cancer cells, NPs promote reactive oxygen species (ROS) production, induce cell cycle arrest and apoptosis, activate ER (endoplasmic reticulum) stress, modulate various signaling pathways, etc. Furthermore, their ability to inhibit tumor growth in vivo has also been documented. In this paper, we have reviewed the role of silver NPs (AgNPs) in cancer nanomedicine, discussing numerous mechanisms by which they render anticancer properties under both in vitro and in vivo conditions, as well as their potential in the diagnosis of cancer. [ABSTRACT FROM AUTHOR]

Cancer is dangerous and one of the major diseases affecting normal human life. In this paper, a fractional-order cancer model with stem cells and chemotherapy is analyzed to check the effects of infection in individuals. The model is investigated by the Sumudu transform and a very effective numerical method. The positivity of solutions with the ABC operator of the proposed technique is verified. Fixed point theory is used to derive the existence and uniqueness of the solutions for the fractional order cancer system. Our derived solutions analyze the actual behavior and effect of cancer disease in the human body using different fractional values. Modern mathematical control with the fractional operator has many applications including the complex and crucial study of systems with symmetry. Symmetry analysis is a powerful tool that enables the user to construct numerical solutions of a given fractional differential equation in a fairly systematic way. Such an analysis will provide a better understanding to control the of cancer disease in the human body. [ABSTRACT FROM AUTHOR]

A key challenge for drug dosing schedules is the ability to learn an optimal control policy even when there is a paucity of accurate information about the systems. Artificial intelligence has great potential for shaping a smart control policy for the dosage of drugs for any treatment. Motivated by this issue, in the present research paper a Caputo–Fabrizio fractional-order model of cancer chemotherapy treatment was elaborated and analyzed. A fix-point theorem and an iterative method were implemented to prove the existence and uniqueness of the solutions of the proposed model. Afterward, in order to control cancer through chemotherapy treatment, a fuzzy-reinforcement learning-based control method that uses the State-Action-Reward-State-Action (SARSA) algorithm was proposed. Finally, so as to assess the performance of the proposed control method, the simulations were conducted for young and elderly patients and for ten simulated patients with different parameters. Then, the results of the proposed control method were compared with Watkins's Q-learning control method for cancer chemotherapy drug dosing. The results of the simulations demonstrate the superiority of the proposed control method in terms of mean squared error, mean variance of the error, and the mean squared of the control action—in other words, in terms of the eradication of tumor cells, keeping normal cells, and the amount of usage of the drug during chemotherapy treatment. [ABSTRACT FROM AUTHOR]

The rise of primary topical monotherapy with chemotherapeutic drugs and immunomodulatory agents represents an increasing recognition of the medical management of ocular surface squamous neoplasia (OSSN), which may replace surgery as the standard of care in the future. Currently, there is no consensus regarding the best way to manage OSSN with no existing guidelines to date. This paper seeks to evaluate evidence surrounding available treatment modalities and proposes an approach to management. The approach will guide ophthalmologists in selecting the most appropriate treatment regime based on patient and disease factors to minimize treatment related morbidity and improve OSSN control. Further work can be done to validate this algorithm and to develop formal guidelines to direct the management of OSSN. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver metastases occur in almost half of patients with colorectal cancer, either at the time of presentation (synchronous) or eventually as a metachronous recurrence of the disease. Approximately one quarter of patients with metastasis to the liver receive surgical resection with curative intent but recurrence is frequent and related to tumor biology. Understanding cancer biology is crucial to improve outcomes. In an attempt at unveiling novel targets for treatment, this paper investigates and summarizes current knowledge of the distinct growth patterns of tumor cells at the interface with normal liver tissue, defined as the histopathological growth pattern, and their interaction with immune cells in the microenvironment. Almost half of all patients with colorectal cancer present with or eventually develop metastasis, most frequently in the liver. Understanding the histopathological growth patterns and tumor immune microenvironment of colorectal liver metastases may help determine treatment strategies and assess prognosis. A literature search was conducted to gather information on cancer biology, histopathological growth patterns, and the tumor immune microenvironment in colorectal liver metastases, including their mechanisms and their impact on clinical outcomes. A first consensus on histopathological growth patterns emerged in 2017, identifying five growth patterns. Later studies found benefits from a two-tier system, desmoplastic and non-desmoplastic, incorporated into the updated 2022 consensus. Furthermore, the tumor immune microenvironment shows additional characteristic features with relevance to cancer biology. This includes density of T-cells (CD8+), expression of claudin-2, presence of vessel co-option versus angiogenesis, as well as several other factors. The relation between histopathological growth patterns and the tumor immune microenvironment delineates distinct subtypes of cancer biology. The distinct subtypes are found to correlate with risk of metastasis or relapse, and hence to clinical outcome and long-term survival in each patient. In order to optimize personalized and precision therapy for patients with colorectal liver metastases, further investigation into the mechanisms of cancer biology and their translational aspects to novel treatment targets is warranted. [ABSTRACT FROM AUTHOR]