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Targeted cancer therapy (TCT) is gaining increased interest because it reduces the risks of adverse side effects by specifically treating tumor cells. TCT testing has traditionally been performed using two-dimensional (2D) cell culture and animal studies. Organ-on-a-chip (OoC) platforms have been developed to recapitulate cancer in vitro, as cancer-on-a-chip (CoC), and used for chemotherapeutics development and testing. This review explores the use of CoCs to both develop and test TCTs, with a focus on three main aspects, the use of CoCs to identify target biomarkers for TCT development, the use of CoCs to test free, un-encapsulated TCTs, and the use of CoCs to test encapsulated TCTs. Despite current challenges such as system scaling, and testing externally triggered TCTs, TCToC shows a promising future to serve as a supportive, pre-clinical platform to expedite TCT development and bench-to-bedside translation., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Purpose: To establish thresholds in the Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference, physical function, fatigue, and depression scores on the basis of their association with subsequent use of the emergency department (ED) or urgent care by people diagnosed with cancer., Methods: Retrospective data from 952 people seen at Henry Ford Cancer and insured through the Health Alliance Plan were analyzed using generalized linear mixed-effects models. The log odds of ED or urgent care use during 14 or 30 days after each patient-reported outcome (PRO) assessment were related to PRO scores, while adjusting for comorbidity, sociodemographic, and tumor characteristics., Results: Pain interference and physical function were associated with subsequent ED or urgent care visits, but fatigue and depression were not, and the results for 14- and 30-day visits were similar. Thresholds anchored in the likelihood of these visits differed according to cancer stage. For people with advanced cancer, a pain interference score of 60 or higher (odds ratio [OR] 3.75, [95% CI, 1.53 to 7.87]) and a physical function score lower than 40 (OR 2.94, [95% CI, 1.22 to 7.06]) produced the largest ORs with narrowest CIs for 30-day visits. For people with nonadvanced cancer, the thresholds of 65 for pain interference (OR 2.64, [95% CI, 1.40 to 5.01]) and 35 for physical function (OR 1.87, [95% CI, 1.01 to 3.45]) produced largest ORs with narrowest CIs for 30-day visits., Conclusion: These anchor-based thresholds in PROMIS scores can inform clinicians' actions with the goal of preventing ED or urgent care visits.

MAPK has been reported as a key oncogenic pathway for canine histiocytic sarcoma, which can be pharmacologically targeted with trametinib, a small inhibitor of MEK1/2. Preliminary data showed promising antitumor activity in in vitro and in vivo models and represented a proof of concept to translate the findings from bench to bedside. In this phase I, dose escalating study using a 3 + 3 cohort design, trametinib was evaluated in 18 dogs with cancer. Adverse events were graded according to VCOG-CTCAE v2. Blood samples and tumour biopsies were collected for pharmacokinetic and pharmacodynamic assessment. Trametinib was well tolerated with a maximum tolerated dose of 0.5 mg/m 2 /day, PO. Dose-limiting toxicities included systemic hypertension, proteinuria, lethargy and elevated ALP, and were all Grade 3. The drug exposures increased more than linearly with dose since the elimination of trametinib was saturable. At a dose of 500 μg Q24h (0.5 mg/m 2 /day in a 30 kg dog), approximately 70% of dogs had an average steady-state concentration of 10 ng/mL, achieved after approximately 2 weeks. This threshold was associated with clinical efficacy in humans. Target engagement was not observed in biospecimens collected on Days 0 and 7. In conclusion, trametinib was considered safe in dogs with cancer, and the dose of 0.5 mg/m 2 /day was the recommended dose for phase II studies., (© 2024 The Author(s). Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

We evaluate deconvolution methods, which infer levels of immune infiltration from bulk expression of tumor samples, through a community-wide DREAM Challenge. We assess six published and 22 community-contributed methods using in vitro and in silico transcriptional profiles of admixed cancer and healthy immune cells. Several published methods predict most cell types well, though they either were not trained to evaluate all functional CD8+ T cell states or do so with low accuracy. Several community-contributed methods address this gap, including a deep learning-based approach, whose strong performance establishes the applicability of this paradigm to deconvolution. Despite being developed largely using immune cells from healthy tissues, deconvolution methods predict levels of tumor-derived immune cells well. Our admixed and purified transcriptional profiles will be a valuable resource for developing deconvolution methods, including in response to common challenges we observe across methods, such as sensitive identification of functional CD4+ T cell states., (© 2024. The Author(s).)

Introduction: The number of older adults who are cancer survivors is rapidly growing. Evidence is needed to inform interventions to support successful aging among older adults (including older adult cancer survivors). Active engagement with life, that is, spending time with family and/or close friends, may be related to health outcomes, but this concept remains understudied., Methods: We used survey data to assess active engagement among older adults (ages 50 + years) from seven mid-Atlantic US states (n = 2,914), and geocoded their residence to collect collected measures of community availability of social interaction. Outcomes were physical and mental health-related quality of life (HRQoL), assessed with the SF-12. We used multivariable, multilevel linear regression to evaluate relationships between social interactions (i.e., "active engagement with life," or visiting with family and/or friends at least once per week and having at least three close friends, and community-level availability, measured with census tract-level park land and walkability and with county-level availability of social associations) and HRQoL. Finally, we explored differences in these relationships by recent cancer survivorship., Results: Overall, 1,518 (52.3%) participants were actively engaged. Active engagement was associated with higher physical HRQoL (estimate = 0.94, standard error [SE] = 0.46, p = .04) and mental HRQoL (estimate = 2.10, SE = 0.46, p < .001). The relationship between active engagement and physical HRQoL was stronger for recent cancer survivors (estimate = 4.95, SE = 1.84, p < .01) than for the general population (estimate = 1.10, SE = 0.43, p = .01). Community-level availability of social interaction was not associated with HRQoL., Conclusion: Our analysis demonstrated promising associations between active engagement with life and HRQoL among older adults, with large benefits for older cancer survivors. Additional research is needed on how active engagement is associated with better HRQoL, which can inform future policies and programs to optimize the aging process in the US., (© 2024. The Author(s).)

The burgeoning field of cancer theranostics has witnessed advancements through the development of targeted molecular agents, particularly peptides. These agents exploit the overexpression or mutations of specific receptors, such as the Epidermal Growth Factor receptor (EGFR) and α V β 3 integrin, which are pivotal in tumor growth, angiogenesis, and metastasis. Despite the extensive research into and promising outcomes associated with antibody-based therapies, peptides offer a compelling alternative due to their smaller size, ease of modification, and rapid bioavailability, factors which potentially enhance tumor penetration and reduce systemic toxicity. However, the application of peptides in clinical settings has challenges. Their lower binding affinity and rapid clearance from the bloodstream compared to antibodies often limit their therapeutic efficacy and diagnostic accuracy. This overview sets the stage for a comprehensive review of the current research landscape as it relates to EGFR- and integrin α V β 3 -targeting peptides. We aim to delve into their synthesis, radiolabeling techniques, and preclinical and clinical evaluations, highlighting their potential and limitations in cancer theranostics. This review not only synthesizes the extant literature to outline the advancements in peptide-based agents targeting EGFR and integrin α V β 3 but also identifies critical gaps that could inform future research directions. By addressing these gaps, we contribute to the broader discourse on enhancing the diagnostic precision and therapeutic outcomes of cancer treatments.

Background: Tunneled central venous catheters (CVCs) are the cornerstone of modern oncologic practice. Establishing best practices for catheter management in children with cancer is essential to optimize care, but few guidelines exist to guide placement and management., Objectives: To address four questions: 1) Does catheter composition influence the incidence of complications; 2) Is there a platelet count below which catheter placement poses an increased risk of complications; 3) Is there an absolute neutrophil count (ANC) below which catheter placement poses an increased risk of complications; and 4) Are there best practices for the management of a central line associated bloodstream infection (CLABSI)?, Methods: Data Sources: English language articles in Ovid Medline, PubMed, Embase, Web of Science, and Cochrane Databases., Study Selection: Independently performed by 2 reviewers, disagreements resolved by a third reviewer., Data Extraction: Performed by 4 reviewers on forms designed by consensus, quality assessed by GRADE methodology., Results: Data were extracted from 110 manuscripts. There was no significant difference in fracture rate, venous thrombosis, catheter occlusion or infection by catheter composition. Thrombocytopenia with minimum thresholds of 30,000-50,000 platelets/mcl was not associated with major hematoma. Limited evidence suggests a platelet count <30,000/mcL was associated with small increased risk of hematoma. While few studies found a significant increase in CLABSI in CVCs placed in neutropenic patients with ANC<500Kcells/dl, meta-analysis suggests a small increase in this population. Catheter removal remains recommended in complicated or persistent infections. Limited evidence supports antibiotic, ethanol, or hydrochloric lock therapy in definitive catheter salvage. No high-quality data were available to answer any of the proposed questions., Conclusions: Although over 15,000 tunneled catheters are placed annually in North America into children with cancer, there is a paucity of evidence to guide practice, suggesting multiple opportunities to improve care., Level of Evidence: III. This study was registered as PROSPERO 2019 CRD42019124077., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cancer peer support groups are crucial in improving quality of life outcomes and extending cancer survival. Using the Health Belief Model (HBM) and Theory of Planned Behavior (TPB) as guiding frameworks, this study examined perceptions of telehealth-based cancer support groups among individuals treated for cancer at a rural oncology program. We distributed online surveys to 34 survivors or individuals undergoing cancer treatment who actively participated in virtual cancer support groups, achieving a 79.4% response rate (27 participants). The survey, blending quantitative and qualitative methodologies, assessed demographic characteristics, overall telehealth satisfaction, satisfaction with telehealth-based peer support, and perceived social support. Quantitative data were analyzed using descriptive statistics, while qualitative responses were examined through template analysis, focusing on the HBM and TPB constructs. Participants expressed general satisfaction with telehealth and indicated a willingness to use telehealth services again. Participants cited ease of use and broader access to cancer support groups with telehealth approaches. Barriers to telehealth included the lack of interpersonal connection, internet access, and technical difficulties. The findings underscore the nuanced perceptions of telehealth-based cancer support groups in a rural oncology setting. Despite acknowledging telehealth's limitations, participants appreciated its role in facilitating access to support. The findings provide valuable insights for optimizing digital health interventions, emphasizing the need for a balanced approach that considers both the potential and the challenges of telehealth in cancer care. This study offers critical guidance in optimizing digital health interventions and ensuring accessible, effective support for cancer patients in rural areas., (© 2024. The Author(s) under exclusive licence to American Association for Cancer Education.)

Postoperative delirium (POD) after cancer surgeries can be a result of chemo brain, anesthesia, surgery duration, and preoperative cognitive impairment. Although older age and preoperative cognitive dysfunction were reported to increase the risk of POD in noncardiac surgery, the role of preoperative cognitive function and age in the development of POD after all types of cancer surgeries is not clear. This study aimed to determine the relationship between preoperative cognitive function and likelihood of POD after cancer surgeries. This study used three main online databases and followed PRISMA guidelines. English language original articles that examined preoperative cognitive function before solid tumor cancer surgery and assessed patients for postoperative delirium were included. We employed the random effect meta-analysis method. The overall incidence of POD ranged from 8.7% to 50.9%. The confusion assessment method was the most common tool used to assess delirium. Mini-mental state evaluation (MMSE), Mini-cog, and Montreal cognitive assessment were the most common tools to assess cognitive function. The pooled (total observation = 4676) random effects SMD was estimated at -0.84 (95% confidence interval [CI]: -1.30 to -0.31), indicating that lower MMSE scores before surgery are associated with a higher risk of POD. The pooled (total observation = 2668) random effects OR was estimated at 5.17 (95% CI: 2.51 to -10.63), indicating preoperative cognitive dysfunction can significantly predict the occurrence of POD after cancer surgeries. In conclusion, preoperative cognitive function is an independent and significant predictor of POD after solid tumor cancer surgeries., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Gene expression profiling of new or modified cell lines becomes routine today; however, obtaining comprehensive molecular characterization and cellular responses for a variety of cell lines, including those derived from underrepresented groups, is not trivial when resources are minimal. Using gene expression to predict other measurements has been actively explored; however, systematic investigation of its predictive power in various measurements has not been well studied. Here, we evaluated commonly used machine learning methods and presented TransCell, a two-step deep transfer learning framework that utilized the knowledge derived from pan-cancer tumor samples to predict molecular features and responses. Among these models, TransCell had the best performance in predicting metabolite, gene effect score (or genetic dependency), and drug sensitivity, and had comparable performance in predicting mutation, copy number variation, and protein expression. Notably, TransCell improved the performance by over 50% in drug sensitivity prediction and achieved a correlation of 0.7 in gene effect score prediction. Furthermore, predicted drug sensitivities revealed potential repurposing candidates for new 100 pediatric cancer cell lines, and predicted gene effect scores reflected BRAF resistance in melanoma cell lines. Together, we investigated the predictive power of gene expression in six molecular measurement types and developed a web portal (http://apps.octad.org/transcell/) that enables the prediction of 352,000 genomic and cellular response features solely from gene expression profiles., (© The Author(s) 2024. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.)

Telomere length (TL) is an important indicator of cellular aging. Shorter TL is associated with several age-related diseases including coronary heart disease, heart failure, diabetes, osteoporosis, and cancer. Recently, a DNA methylation-based TL (DNAmTL) estimator has been developed as an alternative method for directly measuring TL. In this study, we examined the association of DNAmTL with cancer prevalence and mortality risk among people with and without HIV in the Veterans Aging Cohort Study Biomarker Cohort (VACS, N = 1917) and Women's Interagency HIV Study Cohort (WIHS, N = 481). We profiled DNAm in whole blood (VACS) or in peripheral blood mononuclear cells (WIHS) using an array-based method. Cancer prevalence was estimated from electronic medical records and cancer registry data. The VACS Index was used as a measure of physiologic frailty. Models were adjusted for self-reported race and ethnicity, batch, smoking status, alcohol consumption, and five cell types (CD4, CD8, NK, B cell, and monocyte). We found that people with HIV had shorter average DNAmTL than those without HIV infection [beta = -0.25, 95% confidence interval (-0.32, -0.18), p = 1.48E-12]. Greater value of VACS Index [beta = -0.002 (-0.003, -0.001), p = 2.82E-05] and higher cancer prevalence [beta = -0.07 (-0.10, -0.03), p = 1.37E-04 without adjusting age] were associated with shortened DNAmTL. In addition, one kilobase decrease in DNAmTL was associated with a 40% increase in mortality risk [hazard ratio: 0.60 (0.44, 0.82), p = 1.42E-03]. In summary, HIV infection, physiologic frailty, and cancer are associated with shortening DNAmTL, contributing to an increased risk of all-cause mortality., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Objective: To evaluate social drivers of health and how they impact pediatric oncology patients' clinical outcomes during pediatric intensive care unit (PICU) admission via correlation with patient ZIP codes., Methods: Demographic, clinical, and outcome variables from Virtual Pediatric Systems®, LLC for oncology patients (2009-2021) in California PICUs (excluding postoperative) using 3-digit ZIP Codes with social drivers of health variables linguistic isolation, poverty, race/ethnicity, and education abstracted from American Community Survey data for 3-digit ZIP Codes using the Environmental Protection Agency's EJScreen tool. Outcomes of length of stay (LOS), mortality, acuity scores, were compared with social variables., Results: Positive correlation between mortality and minority racial groups (Hispanic/Latino) across ZIP Codes (correlation coefficients of 0.45 (95% CI: 0.22-0.64, p < 0.001) in 2017, 0.50 (95% CI: 0.27-0.68, p < 0.001) in 2018, 0.33 (95% CI: 0.07-0.54, p = 0.013) in 2020, and 0.32 (95% CI: 0.06-0.53, p = 0.018) in 2021). Median PICU length of stay significantly correlated with linguistic isolation (coefficient of 0.42 (95% CI: 0.18-0.61, p = 0.001) in 2021 versus -0.41 (95% CI: -0.61 to -0.16, p = 0.002) in 2019), which included PRISMIII (n = 7417). Mixed effects logistic regression model for other constant variables (PRISMIII, cancer type, race/ethnicity, year), random effect of patient, linguistic isolation (percentage as a continuous value) was significantly associated (95% CI: 1.01-1.06; p = 0.02) with mortality; (OR = 1.03)., Conclusions: Linguistic isolation was correlated with LOS and mortality, however variable year to year., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Although radiotherapy continues to evolve as a mainstay of the oncological armamentarium, research and innovation in radiotherapy in low-income and middle-income countries (LMICs) faces challenges. This third Series paper examines the current state of LMIC radiotherapy research and provides new data from a 2022 survey undertaken by the International Atomic Energy Agency and new data on funding. In the context of LMIC-related challenges and impediments, we explore several developments and advances-such as deep phenotyping, real-time targeting, and artificial intelligence-to flag specific opportunities with applicability and relevance for resource-constrained settings. Given the pressing nature of cancer in LMICs, we also highlight some best practices and address the broader need to develop the research workforce of the future. This Series paper thereby serves as a resource for radiation professionals., Competing Interests: Declaration of interests RK reports receiving support from the University of Utah Huntsman Cancer Institute for attending meetings and for travel. PGSP declares support from the National Cancer Institute's Radiation Research Program for contributions to this Series paper and for attending meetings and conferences. MM reports receiving grants from the Australian National Health and Medical Research Council for clinical trials paid to his institution; a grant for an investigator-initiated clinical trial that Varian has agreed to, but the payment of this grant is pending; travel support from Varian to deliver a presentation at a national research meeting; and honoraria for lectures from Varian that have been donated to his institution. PK is a recipient of grants from the Australian Government National Health and Medical Research Council and the Cancer Institute NSW Translational Program; has US patents on MRI-LINAC radiotherapy and x-ray-guided radiotherapy; and has stock in SeeTreat. NAM is a recipient of payment for expert testimony as a consultant in a medical legal case whose subject matter was unrelated to the field of research in this manuscript; and has served in a leadership role on the committee of the Radiosurgery Society: the Clinical Working Group of the GRID, LATTICE, Microbeam, and FLASH Working Group. BAJ-F is a recipient of institutional grants from Accuray, the Italian Association for Cancer Research, and the Fondazione Instituto Europeo di Oncologia-Centro Cardiologico Monzino for her institution; has received honoraria from the European Society for Radiotherapy and Oncology for lectures and presentations, from the European School of Oncology and the American Society of Clinical Oncology for lectures and masterclasses, and from Roche, Bayer, Janssen, Carl Zeiss, Accuray, Astellas, Elekta, IBA, Technologie Avanzate, and ACCMED for lectures; and has participated on advisory boards for Janssen, AstraZeneca, and Bayer, and on a steering committee for Seagen. AA reports receiving an Advanced Fellowship from the National Institute for Health Research. F-MSK has received research grants from Varian Medical, Merck, and Shenzhen Science and Technology Commission Programme (KQTD20180411185028798); she has also received a speaker's honorarium from AstreZeneca. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Treatment for childhood solid tumors may lead to an increased risk for gonadal dysfunction/infertility. Discussion of risk should occur at diagnosis, any changes in therapy, and during survivorship. Gonadotoxic therapies were abstracted from 32 Children's Oncology Group (COG) phase III, frontline solid tumor protocols, in use from 2000 to 2022. Risk for gonadal dysfunction/infertility was assessed based on gonadotoxic therapies, sex, and pubertal status and assigned as minimal, significant, and high following the Oncofertility Consortium Pediatric Initiative Network (PIN) risk stratification. Most protocols (65.6%, 21/32) contained at least one therapeutic arm with a high level of increased risk. Solid tumor therapies present challenges in risk stratification due to response-adjusted therapy and the need to account for radiation field in the risk assessment. This guide hopes to serve as a tool to assist in standardizing gonadotoxic risk assessments across disciplines and improve referral for fertility services and reproductive health counseling for patients receiving COG-based solid tumor therapy. Internationally, many solid tumor therapies follow similar paradigms to COG studies, and risk stratifications may be generalizable to similar styles of therapy. In addition, this model may be applied to other international groups with the goal of standardizing fertility assessments., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Cancer is the result of genetic abnormalities that cause normal cells to grow into neoplastic cells. Cancer is characterized by several distinct features, such as uncontrolled cell growth, extensive spreading to other parts of the body, and the ability to resist treatment. The scientists have stressed the development of nanostructures as novel therapeutic options in suppressing cancer, in response to the emergence of resistance to standard medicines. One of the specific mechanisms with dysregulation during cancer is autophagy. Nanomaterials have the ability to specifically carry medications and genes, and they can also enhance the responsiveness of tumor cells to standard therapy while promoting drug sensitivity. The primary mechanism in this process relies on autophagosomes and their fusion with lysosomes to break down the components of the cytoplasm. While autophagy was initially described as a form of cellular demise, it has been demonstrated to play a crucial role in controlling metastasis, proliferation, and treatment resistance in human malignancies. The pharmacokinetic profile of autophagy modulators is poor, despite their development for use in cancer therapy. Consequently, nanoparticles have been developed for the purpose of delivering medications and autophagy modulators selectively and specifically to the cancer process. Furthermore, several categories of nanoparticles have demonstrated the ability to regulate autophagy, which plays a crucial role in defining the biological characteristics and response to therapy of tumor cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Introduction: Socio-psychological factors such as fear of recurrence and presence of social support may affect quality of life (QOL) of cancer patients. Identifying mediating factors that impact QOL are crucial for targeting vulnerability in patients undergoing cancer treatments. The study purpose was therefore to determine relationships between presence of fear of cancer recurrence and QOL of patients, with the mediating role of social support., Methods: A predictive correlational design was used to conduct the study with 300 patients with cancer who were undergoing chemotherapy, radiotherapy, or surgery at two medical centers in Tehran. Measures included a demographic information form, the Fear of Cancer Recurrence Inventory (FCRI), the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), and the Multidimensional Scale of Perceived Social Support (MSPSS). Data analyses included descriptives, and path analysis analyses., Results: Higher fear of cancer recurrence predicted lower QOL (β = -0.60, p < 0.001). Moreover, individuals with lower fear of cancer recurrence also perceived higher social support (β = 0.32, p < 0.001). Additionally, individuals with higher perceived social support also reported better QOL (β = 0.30, p < 0.001)., Conclusion: Perceived social support plays a significant mediating role in the relationship between the fear of cancer recurrence and QOL in patients undergoing active cancer treatment. Enhancing social support among cancer patients may contribute to enhanced QOL, and as does reducing fears associated with disease recurrence.

Background: Cancer is a heterogeneous disease driven by complex molecular alterations. Cancer subtypes determined from multi-omics data can provide novel insight into personalised precision treatment. It is recognised that incorporating prior weight knowledge into multi-omics data integration can improve disease subtyping., Methods: We develop a weighted method, termed weight-boosted Multi-Kernel Learning (wMKL) which incorporates heterogeneous data types as well as flexible weight functions, to boost subtype identification. Given a series of weight functions, we propose an omnibus combination strategy to integrate different weight-related P-values to improve subtyping precision., Results: wMKL models each data type with multiple kernel choices, thus alleviating the sensitivity and robustness issue due to selecting kernel parameters. Furthermore, wMKL integrates different data types by learning weights of different kernels derived from each data type, recognising the heterogeneous contribution of different data types to the final subtyping performance. The proposed wMKL outperforms existing weighted and non-weighted methods. The utility and advantage of wMKL are illustrated through extensive simulations and applications to two TCGA datasets. Novel subtypes are identified followed by extensive downstream bioinformatics analysis to understand the molecular mechanisms differentiating different subtypes., Conclusions: The proposed wMKL method provides a novel strategy for disease subtyping. The wMKL is freely available at https://github.com/biostatcao/wMKL ., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Context: Late or residual symptoms diminish quality of life for many cancer survivors after completion of treatment., Objectives: Examine risk factors associated with persisting symptom burden after chemotherapy and the lack of symptom improvement over time., Methods: Survivors who completed curative-intent chemotherapy within two years for solid tumors were enrolled into a symptom management trial. There were 375 survivors with two or more comorbid conditions or one comorbid condition and elevated depressive symptoms (pre-defined risk factors in the trial design) who received interventions and 71 survivors without these risk factors who did not receive interventions. For all survivors, symptoms were assessed at intake, 4, and 13 weeks and categorized as mild, moderate, or severe based on the interference with daily life. The probabilities of moderate or severe symptoms and symptom improvement were analyzed using generalized mixed-effects models in relation to comorbidity, depressive symptoms, age, sex, race/ethnicity, employment, time since chemotherapy completion, and physical function. Multiple symptoms were treated as nested within the survivor., Results: Moderate or severe symptoms at baseline and the lack of improvement over time were associated with younger age and lower physical function over and above a greater number of comorbidities and elevated severity of depressive symptoms., Conclusion: Risk factors identified in this research (younger age, lower physical function, greater comorbidity, and higher depressive symptoms) can be used to allocate resources for post-treatment symptom management for cancer survivors in order to relieve symptoms that do not necessarily resolve with time., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Cancer has remained a formidable challenge in medicine and has claimed an enormous number of lives worldwide. Theranostics, combining diagnostic methods with personalized therapeutic approaches, shows huge potential to advance the battle against cancer. This review aims to provide an overview of theranostics in oncology: exploring its history, current advances, challenges, and prospects. We present the fundamental evolution of theranostics from radiotherapeutics, cellular therapeutics, and nanotherapeutics, showcasing critical milestones in the last decade. From the early concept of targeted drug delivery to the emergence of personalized medicine, theranostics has benefited from advances in imaging technologies, molecular biology, and nanomedicine. Furthermore, we emphasize pertinent illustrations showcasing that revolutionary strategies in cancer management enhance diagnostic accuracy and provide targeted therapies customized for individual patients, thereby facilitating the implementation of personalized medicine. Finally, we describe future perspectives on current challenges, emerging topics, and advances in the field., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: A cancer diagnosis can be psychologically challenging to individuals due to perceptions that the disease is potentially incurable truncating life expectancy. The purpose of the study was to examine the relationships among religious well-being, existential well-being, fear of progression and quality of life in Iranian patients with cancer and to evaluate the potential mediating role of hope on these relationships., Methods: This study with predictive cross-sectional design was done in 2023. Data was gathered from 398 patients with cancer that was selected with accessible sampling method from cancer center of Mazandaran university of medical sciences (Sari, Iran). Study constructs included the religious and existential wellbeing, cancer fear of progression, Snyder Hope, and quality of life. Analysis of a Moment Structures (AMOS) software (v27) was utilized for all study analyses. Covariance based-structural equation modeling (SEM) was used to assess the mediating role of hope., Results: The mean age of patients with cancer was 49.14 (SD = 16.16). The results of the direct effect showed a significant positive relationship between religious well-being and hope (B = 0.164, p < .001), and between hope and quality of life (B = 0.212, p < 0.001). Also, significant negative relationship between fear of progression and hope (B = -0.147, p < 0.05) was founded., Conclusion: A significant positive relationship between hope and quality of life, as well as religious well-being and hope, suggests the influential effects of hope and religious well-being on improving quality of life in patients with cancer. Negative relationships between fear of progression and hope conclude that managing fear of progression may be an important factor in increasing hope and improving quality of life in patients with cancer.

Background: Postoperative inpatients experience increased stress due to pain and poor restorative sleep than non-surgical inpatients., Objectives and Methods: A total of 101 patients, undergoing major oncologic surgery, were randomized to a postoperative sleep protocol (n = 50) or standard postoperative care (n = 51), between August 2020 and November 2021. The primary endpoint of the study was postoperative sleep time after major oncologic surgery. Sleep time and steps were measured using a Fitbit Charge 4®., Results: There was no statistically significant difference found in postoperative sleep time between the sleep protocol and standard group (median sleep time of 427 min vs. 402 min; p = 0.852, respectively). Major complication rates were similar in both groups (7.4% vs. 8.9%). Multivariate analysis found sex and Charlson Comorbidity Index to be significant factors affecting postoperative sleep time and step count. Postoperative delirium was only observed in the standard group, although this did not reach statistical significance. There were no in hospital mortalities., Conclusion: The use of a sleep protocol was found to be safe in our study population. There was no statistical difference in postoperative sleep time or major complications. Institution of a more humane sleep protocol for postoperative inpatients should be considered., (© 2023 Wiley Periodicals LLC.)

There is great enthusiasm toward the development of novel immunotherapies for the treatment of cancer, and given their roles in immune system regulation, chemokines stand out as promising candidates for use in new cancer therapies. Many previous studies have shown how chemokine signaling pathways could be targeted to halt cancer progression. We and others have revealed that the chemokine CXCL14 promotes antitumor immune responses, suggesting that CXCL14 may be effective for cancer immunotherapy. However, it is still unknown what mechanism governs CXCL14-mediated antitumor activity, how to deliver CXCL14, what dose to apply, and what combinations with existing therapy may boost antitumor immune responses in cancer patients. Here, we provide updates on the role of CXCL14 in cancer progression and discuss the potential development and application of CXCL14 as an immunotherapeutic agent.

Purpose: This study examines providers' and clinic staff's perspectives on patient-reported outcomes (PROs) implementation at an academic medical center., Methods: An anonymous and voluntary survey was administered to Henry Ford Cancer providers and clinic staff 18 months after PROs program implementation in September 2020, to obtain their feedback on perceived barriers, impact on workflows, and PROs administration frequency in routine cancer care., Results: A total of 180 providers and 40 clinic staff were invited to complete the survey; 31% and 63% completed the survey, respectively. Approximately 68% of providers reported that electronically integrated PROs scores were either beneficial or somewhat beneficial to their patients, while only 28% of the clinic staff reported that PROs were beneficial or somewhat beneficial to patients. According to the clinic staff, the most common barriers to PROs completion included lack of patients' awareness of the utility of the program with respect to their care, patients' health status at check-in, and PROs being offered too frequently., Conclusion: There is favorable acceptance of the PROs program by providers, but clinic staff found it less favorable. Interventions to address barriers and improve program engagement are needed to ensure broad adoption of PROs in oncology practice., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Dose heterogeneity within a tumor target is likely responsible for the biologic effects and local tumor control from spatially fractionated radiation therapy (SFRT). This study used a commercially available GRID-pattern dose mudulated nonuniform radiation therapy (GRID) collimator to assess the interplan variability of heterogeneity dose metrics in patients with various bulky tumor sizes and depths., Methods and Materials: The 3-dimensional heterogeneity metrics of 14 bulky tumors, ranging from 155 to 2161 cm 3 in volume, 6 to 23 cm in equivalent diameter, and 3 to 13 cm in depth, and treated with GRID collimator-based SFRT were studied. A prescription dose of 15 Gy was given at the tumor center with 6 MV photons. The dose-volume histogram indices, dose heterogeneity parameters, and peak/valley dose ratios were derived; the equivalent uniform doses of cancer cells with various radiosensitivities in each plan were estimated. To account for the spatial fractionation, high dose core number density of the tumor target was defined and calculated., Results: Among 14 plans, the dose-volume histogram indices D5, D10, D50, D90, and D95 (doses covering 5%, 10%, 50%, 90%, and 95% of the target volume) were found within 10% variation. The dose ratio of D10/D90 also showed a moderate consistency (range, 3.9-5.0; mean, 4.4). The equivalent uniform doses were consistent, ranging from 4.3 to 5.5 Gy, mean 4.6 Gy, for radiosensitive cancer cells and from 5.8 to 6.9 Gy, mean 6.2 Gy, for radioresistant cancer cells. The high dose core number density was within 20% among all plans., Conclusions: GRID collimator-based SFRT delivers a consistent heterogeneity dose distribution and high dose core density across bulky tumor plans. The interplan reproducibility and simplicity of GRID therapy may be useful for certain clinical indications and interinstitutional clinical trial design, and its heterogeneity metrics may help guide multileaf-collimator-based SFRT planning to achieve similar or further optimized dose distributions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The acidic pH of tumor tissue has been used to trigger drug release from nanoparticles. However, dynamic interactions between tumor pH and vascularity present challenges to optimize therapy to particular microenvironment conditions. Despite recent development of pH-sensitive nanomaterials that can accurately quantify drug release from nanoparticles, tailoring release to maximize tumor response remains elusive. This study hypothesizes that a computational modeling-based platform that simulates the heterogeneously vascularized tumor microenvironment can enable evaluation of the complex intra-tumoral dynamics involving nanoparticle transport and pH-dependent drug release, and predict optimal nanoparticle parameters to maximize the response. To this end, SPNCD nanoparticles comprising superparamagnetic cores of iron oxide (Fe 3 O 4 ) and a poly(lactide- co -glycolide acid) shell loaded with doxorubicin (DOX) were fabricated. Drug release was measured in vitro as a function of pH. A 2D model of vascularized tumor growth was calibrated to experimental data and used to evaluate SPNCD effect as a function of drug release rate and tissue vascular heterogeneity. Simulations show that pH-dependent drug release from SPNCD delays tumor regrowth more than DOX alone across all levels of vascular heterogeneity, and that SPNCD significantly inhibit tumor radius over time compared to systemic DOX. The minimum tumor radius forecast by the model was comparable to previous in vivo SPNCD inhibition data. Sensitivity analyses of the SPNCD pH-dependent drug release rate indicate that slower rates are more inhibitory than faster rates. We conclude that an integrated computational and experimental approach enables tailoring drug release by pH-responsive nanomaterials to maximize the tumor response.

Competing Interests: Competing interests: None declared.

Objective: This study compared three ethnic/racial groups of informal cancer caregivers on social determinants of health and tested social determinants of health as predictors of psychological distress and caregiver burden., Methods: This study was a secondary analysis of baseline data of a sequential multiple assignment randomized trial (SMART) testing symptom management interventions with caregiver-survivor dyads. Caregivers completed baseline measures of social determinants of health (SDoH), functional limitations, psychological distress, and caregiver burden. Hispanic, non-Hispanic White, and non-Hispanic other races caregivers were compared on these variables. Multivariate tests of associations between SDoH and caregiver burden and psychological distress were conducted in structural equation modeling with caregiver burden and psychological distress as latent variables., Results: Hispanic caregivers reported significantly higher caregiver burden, specifically for finances, family, and schedules. Caregiver burden was significantly predicted by having income barely or not meeting needs, being female, socially isolated, married, Hispanic, and having poor physical functioning. Significant predictors of caregivers' psychological distress: being female, being socially isolated, and having poor physical functioning., Conclusion: Hispanic caregivers experience significant challenges associated with caregiver burden, especially if they are female, socially isolated, and have poor physical functioning. Assessment of these SDoH is important in caregiver health to provide supportive care during caregiving., Clinical Trial Registration Number: NCT03743415 www.clinicaltrials.gov.

Invariant natural killer T cells (iNKTs) are innate-type T lymphocytes that directly kill tumor cells or tumor-growth promoting immunosuppressive cells such astumor-associated macrophages. Additionally, iNKTs robustly transactivate the antitumor functions of T, B, natural killer, and dendritic cells as well as reinvigorate exhausted immune cells in the tumor microenvironment. As such, iNKTs make excellent candidates for inclusion in anti-cancer cellular therapies. However, to capitalize on the potential benefits of iNKT cell-based approaches, it is imperative that we develop new and clinically viable strategies to enhance their antitumor function. To that end, two novel monoclonal antibodies (mAbs) that selectively bind to the human (NKTT320) or murine (NKT14m) invariant T cell receptor have been recently developed and characterized. Studies using purified human iNKTs (in vitro) and a model of non-human primate (in vivo) reveal that NKTT320 promotes swift, vigorous and sustained iNKT cell activation that is accompanied by robust production of inflammatory mediators and bystander immune cell activation. Furthermore, NKTT320 augments expression of cytotoxic markers and human iNKT cell degranulation. Similarly, NKT14m prompts dramatic murine iNKT cell activation and functional response both in vitro and in vivo. However, antitumor efficacy of a single dose of NKT14m injection in tumor-bearing mice is limited and tumor-model dependent. In contrast, combination treatment of NKT14m with either low dose interleukin (IL)-12 or the chemotherapeutic agent, cyclophosphamide results in a superior antitumor response in vivo. This is evident by activation of both iNKTs and other immune cells, prolonged survival of the tumor-challenged mice, and long-lasting immunity. Collectively, these recent studies justify further development of anti-iTCR mAbs that can be used alone or in conjunction with immunomodulatory agents to enhance iNKT cell antitumor immunity against various cancers.

Telomerase is a complex ribonucleoprotein scaffolded by the telomerase RNA (TR). Telomere lengthening by telomerase is essential to maintain the proliferative potential of stem cells and germ cells, and telomerase is inappropriately activated in the majority of cancers. Assembly of TR with its 12 protein co-factors and the maturation of the 5'- and 3'-ends of TR have been the focus of intense research efforts over the past two decades. High-resolution Cryo-EM structures of human telomerase, high-throughput sequencing of the 3' end of TR, and live cell imaging of various telomerase components have significantly advanced our understanding of the molecular mechanisms that govern telomerase biogenesis, yet many important questions remain unaddressed. In this review, we will summarize these recent advances and highlight the remaining key questions with the ultimate goal of targeting telomerase assembly to suppress telomere maintenance in cancer cells or to promote telomerase activity in patients affected by telomere shortening disorders., (© 2023 The Author(s).)

Upon heterodimerizing with other nuclear receptors, retinoid X receptors (RXR) act as ligand-dependent transcription factors, regulating transcription of critical signaling pathways that impact numerous hallmarks of cancer. By controlling both inflammation and immune responses, ligands that activate RXR can modulate the tumor microenvironment. Several small molecule agonists of these essential receptors have been synthesized. Historically, RXR agonists were tested for inhibition of growth in cancer cells, but more recent drug discovery programs screen new molecules for inhibition of inflammation or activation of immune cells. Bexarotene is the first successful example of an effective therapeutic that molecularly targets RXR; this drug was approved to treat cutaneous T cell lymphoma and is still used as a standard of care treatment for this disease. No additional RXR agonists have yet achieved FDA approval, but several promising novel compounds are being developed. In this review, we provide an overview of the multiple mechanisms by which RXR signaling regulates inflammation and tumor immunity. We also discuss the potential of RXR-dependent immune cell modulation for the treatment or prevention of cancer and concomitant challenges and opportunities., Competing Interests: Declaration of Competing Interest KL & AL are named inventors on patent applications filed on RXR agonists owned by MSU and are founding scientists of Akeila Bio. Other authors have no potential conflicts to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Recently, direct communication with children about cancer seems to have shifted, but little is known about communication regarding discussions of future infertility risk due to cancer therapy. This study conducted cross-cultural comparisons between Japan and the United States to clarify communication patterns about cancer notification and develop appropriate information about fertility issues. Methods: An online survey was distributed to members of the Japanese Society of Pediatric Hematology/Oncology in July 2019 and the American Society of Pediatric Hematology/Oncology in July 2020. Based on the results from the survey, we developed three types of educational videos: a prepubertal version A, B, and a pubertal version. Next, we conducted a survey to assess whether these were appropriate for clinical practice. Results: We analyzed 325 physicians in Japan and 46 in the United States. In Japan, 80.5%, 91.7%, and 92.1% of the physicians notified patients aged 7-9, 10-14, and 15-17 years of their cancer diagnosis directly, respectively, compared within the United States, where the rate was 100%, regardless of age. Further, 9% and 45% of physicians in Japan and the United States, respectively, discuss fertility issues directly with patients aged 7-9 years. In the survey to assess the educational videos, 85% of the physicians preferred to use the educational videos in clinical practice. Conclusion: This is the first step in bringing concordance to communication patters for emerging cancer care around the globe and that this study and its intervention arm provide guidance in ways that ensure global equity in care.

Sialyl Lewis a (sLe a ), also known as cancer antigen 19-9 (CA19-9), is a tumor-associated carbohydrate antigen. The overexpression of sLe a on the surface of a variety of cancer cells makes it an attractive target for anticancer immunotherapy. However, sLe a -based anticancer vaccines have been under-explored. To develop a new vaccine, efficient stereoselective synthesis of sLe a with an amine-bearing linker was achieved, which was subsequently conjugated with a powerful carrier bacteriophage, Qβ. Mouse immunization with the Qβ-sLe a conjugate generated strong and long-lasting anti-sLe a IgG antibody responses, which were superior to those induced by the corresponding conjugate of sLe a with the benchmark carrier keyhole limpet hemocyanin. Antibodies elicited by Qβ-sLe a were highly selective toward the sLe a structure, could bind strongly with sLe a -expressing cancer cells and human pancreatic cancer tissues, and kill tumor cells through complement-mediated cytotoxicity. Furthermore, vaccination with Qβ-sLe a significantly reduced tumor development in a metastatic cancer model in mice, demonstrating tumor protection for the first time by a sLe a -based vaccine, thus highlighting the significant potential of sLe a as a promising cancer antigen., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Abstract: Cancer continues to be the second most common cause of death in the United States. Racially and ethnically minoritized populations continue to experience disparities in cancer prevention compared with majority populations. Multilevel interventions-from policy, communities, health care institutions, clinical teams, families, and individuals-may be uniquely suited to reducing health disparities through behavioral risk factor modification in these populations. The aim of this article is to provide a brief overview of the evidence for primary prevention among racially and ethnically minoritized subpopulations in the United States. We focus on the epidemiology of tobacco use, obesity, diet and physical activity, alcohol use, sun exposure, and smoking, as well as increasing uptake of the Human Papillomavirus Vaccine (HPV), as mutable behavioral risk factors. We describe interventions at the policy level, including raising excise taxes on tobacco products; within communities and with community partners, for safe greenways and parks, and local healthful food; health care institutions, with reminder systems for HPV vaccinations; among clinicians, by screening for alcohol use and providing tailored weight reduction approaches; families, with HPV education; and among individuals, routinely using sun protection. A multilevel approach to primary prevention of cancer can modify many of the risk factors in racially and ethnically minoritized populations for whom cancer is already a burden., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To establish a consensus for initial evaluation and follow-up of patients on active surveillance (AS) for T1 renal masses (T1RM)., Methods: A modified Delphi method was used to gather information about AS of T1RM, with a focus on patient selection, timing/type of imaging modality, and triggers for intervention. A consensus panel of Michigan Urological Surgery Improvement Collaborative-affiliated urologists who routinely manage renal masses was formed. Areas of consensus (defined >80% agreement) about T1RM AS were established iteratively via 3 rounds of online questionnaires., Results: Twenty-six Michigan Urological Surgery Improvement Collaborative urologists formed the panel. Consensus was achieved for 321/587 scenarios (54.7%) administered through 124 questions. Life expectancy, age, comorbidity, and renal function were most important for patient selection, with life expectancy ranking first. All tumors <3 cm and all patients with life expectancy <1 year were considered appropriate for AS. Appropriateness also increased with elevated perioperative risk, increasing tumor complexity, and/or declining renal function. Consensus was for multiphasic axial imaging initially (contrast CT for GFR >60 or MRI for GFR >30) with first repeat imaging at 3-6 months and subsequent imaging timing determined by tumor size. Consensus was for chest imaging for tumors >3 cm initially and >5 cm at follow up. Renal biopsy was not felt to be a requirement for entering AS, but useful in several scenarios. Consensus indicated rapid tumor growth as an appropriate trigger for intervention., Conclusion: Our consensus panel was able to achieve areas of consensus to help define a clinically useful and specific roadmap for AS of T1RM and areas for further discussion where consensus was not achieved., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Women face multiple barriers to fertility preservation after cancer diagnosis, but few studies have examined disparities in use of these services., Methods: Women aged 15-39 years diagnosed with cancer during 2004-2015 were identified from the North Carolina Central Cancer Registry and linked to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Women who cryopreserved oocytes or embryos for fertility preservation (n = 96) were compared to women who received gonadotoxic treatment but did not use fertility preservation (n = 7964). Conditional logistic and log-binomial regression were used to estimate odds ratios (ORs) or prevalence ratios (PRs) and 95% confidence intervals (CIs)., Results: Few adolescent and young adult women with cancer in our study (1.2%) used fertility preservation. In multivariable regression, women less likely to use fertility preservation were older at diagnosis (ages 25-29 vs. 35-39: OR = 6.27, 95% CI: 3.35, 11.73); non-Hispanic Black (vs. non-Hispanic White: PR = 0.44, 95% CI: 0.24, 0.79); and parous at diagnosis (vs. nulliparous: PR = 0.24, 95% CI: 0.13, 0.45); or lived in census tracts that were non-urban (vs. urban: PR = 0.12, 95% CI: 0.04, 0.37) or of lower socioeconomic status (quintiles 1-3 vs. quintiles 4 and 5: PR = 0.39, 95% CI: 0.25, 0.61)., Conclusions: Women with cancer who were older, non-Hispanic Black, parous, or living in areas that were non-urban or of lower socioeconomic position were less likely to use fertility preservation., Implications for Cancer Survivors: Clinical and policy interventions are needed to ensure equitable access to fertility services among women facing cancer treatment-related infertility., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Metabolic fitness of T cells is essential for their vitality, which is largely dependent on the behavior of the mitochondria. The nature of mitochondrial behavior in tumor-infiltrating T cells remains poorly understood. In this study, we show that mitofusin-2 (MFN2) expression is positively correlated with the prognosis of multiple cancers. Genetic ablation of Mfn2 in CD8 + T cells dampens mitochondrial metabolism and function and promotes tumor progression. In tumor-infiltrating CD8 + T cells, MFN2 enhances mitochondria-endoplasmic reticulum (ER) contact by interacting with ER-embedded Ca 2+ -ATPase SERCA2, facilitating the mitochondrial Ca 2+ influx required for efficient mitochondrial metabolism. MFN2 stimulates the ER Ca 2+ retrieval activity of SERCA2, thereby preventing excessive mitochondrial Ca 2+ accumulation and apoptosis. Elevating mitochondria-ER contact by increasing MFN2 in CD8 + T cells improves the efficacy of cancer immunotherapy. Thus, we reveal a tethering-and-buffering mechanism of organelle cross-talk that regulates the metabolic fitness of tumor-infiltrating CD8 + T cells and highlights the therapeutic potential of enhancing MFN2 expression to optimize T cell function.

Background: Primary care physicians not only coordinate referrals to oncology services but can play a crucial role in successful fertility preservation referrals in cancer-diagnosed patients. Hence, it is important to assess their knowledge and attitudes towards fertility preservation., Methods: An eighteen-item oncofertility survey was administered to primary care physicians between May 2019 to September 2020.  Results: A total of forty-six responses were received and analysed. About 60% of primary care physicians did not have adequate knowledge about available fertility preservation options and only 26-32% were aware of international guidelines recommending fertility preservation in cancer patients.  Conclusions: Imparting awareness and knowledge of fertility preservation and its options to primary care physicians could enable an integrated cancer care model while also facilitating successful oncofertility referrals in countries like India., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Tholeti P et al.)

Friends and family members of patients with cancer are increasingly relied on to perform critical multifaceted roles in home-based care, such as appointment scheduling and transportation. The demands associated with this ongo.

Camptothecin (CPT) is an attractive natural drug for cancer chemotherapy. However, the poor water solubility, non-targeting feature, and adverse side effects of CPT are significant obstacles to developing an effective anticancer drug. Here, for the first time, 9-thiol-sialic acid (9-SH-Sia) is coupled to CPT by forming a disulfide releasable carbonate linkage, resulting in a novel CPT prodrug (CPT-ss-Sia) that self-assembles into nanostructures in an aqueous solution. Strikingly, CPT-ss-Sia exhibited excellent in vitro properties, including enhanced water solubility, glutathione (GSH)-triggered CPT release, and increased E-lactone ring stability. Furthermore, CPT-ss-Sia had good cancer cell-killing ability comparable to CPT. Intravenous administration of CPT-ss-Sia significantly inhibited the growth of multiple types of tumors. Histological analysis showed that CPT-ss-Sia treatment significantly reduced lesions in tumor-bearing mice compared to CPT treatment. Notably, CPT-ss-Sia treatment did not adversely affect the body weight of the mice. This is the first report of the 9-SH-Sia conjugate-based prodrug. Overall, CPT-ss-Sia has broad clinical application prospects.

Objective: Researchers sought patient feedback on a proposed randomized controlled trial (RCT) in which gynecological cancer patients would modify their diets with intermittent fasting to gain insight into patients' perspectives, receptivity, and potential obstacles. A convenience sample of 47 patients who met the inclusion criteria of the proposed RCT provided their feedback on the feasibility and protocols of the RCT using a multi-method approach consisting of focus groups (n = 8 patients) and surveys (n = 36 patients)., Results: Patients were generally receptive to the concept of intermittent fasting, and many expressed an interest in attempting it themselves. Patients agreed that the study design was feasible in terms of study assessments, clinic visits, and biospecimen collection. Feedback on what could facilitate adherence included convenient appointment scheduling times and the availability of the research team to answer questions. Regarding recruitment, patients offered suggestions for study advertisements, with the majority concurring that a medical professional approaching them would increase their likelihood of participation., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Phosphatidylserine (PS) is a negatively charged phospholipid normally localized to the inner leaflet of the plasma membrane of cells but is externalized onto the cell surface during apoptosis as well as in malignant and infected cells. Consequently, PS may comprise an important molecular target in diagnostics, imaging, and targeted delivery of therapeutic agents. While an array of PS-binding molecules exist, their utility has been limited by their inability to internalize diagnostic or therapeutic payloads. We describe the generation, isolation, characterization, and utility of a PS-binding motif comprised of a carboxylated glutamic acid (GLA) residue domain that both recognizes and binds cell surface-exposed PS, and then unlike other PS-binding molecules is internalized into these cells. Internalization is independent of the traditional endosomal-lysosomal pathway, directly entering the cytosol of the target cell rapidly. We demonstrate that this PS recognition extends to stem cells and that GLA-domain-conjugated probes can be detected upon intravenous administration in animal models of infectious disease and cancer. GLA domain binding and internalization offer new opportunities for specifically targeting cells with surface-exposed PS for imaging and delivery of therapeutics., (© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Certain chemotherapy agents, radiation, and surgery can all negatively impact future fertility. Consults regarding treatment-related risk for infertility and gonadal late effects of these agents should occur at the time of diagnosis as well as during survivorship. Counseling on fertility risk has traditionally varied significantly across providers and institutions. We aim to provide a guide to standardize the assignment of gonadotoxic risk, which can be used in counseling patients both at the time of diagnosis and in survivorship. Gonadotoxic therapies were abstracted from 26 frontline Children's Oncology Group (COG) phase III protocols for leukemia/lymphoma, in use from 2000-2022. A stratification system based on gonadotoxic therapies, sex, and pubertal status was used to assign treatments into minimal, significant, and high level of increased risk for gonadal dysfunction/infertility. Risk levels were assigned to protocols and different treatment arms to aid oncologists and survivor care providers in counseling patients regarding treatment-related gonadotoxicity. Males were most commonly at high risk, with at least one high-risk arm in 14/26 protocols (54%), followed by pubertal females (23% of protocols) and prepubertal females (15% of protocols). All patients who received direct gonadal radiation or hematopoietic stem cell transplant (HSCT) were considered at high risk. Partnering with patients and their oncology/survivorship team is imperative for effective fertility counseling both prior to and post treatment, and this comprehensive guide can be used as a tool to standardize and improve reproductive health counseling in patients undergoing COG-based leukemia/lymphoma care., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Objective: To investigate the association between infertility and the incidence of invasive cancer., Design: Prospective cohort study (1989-2015)., Setting: Not applicable., Patient(s): A total of 103,080 women aged 25-42 years in the Nurses' Health Study II who were cancer-free at baseline (1989)., Intervention(s): The infertility status (failure to conceive after 1 year of regular, unprotected sex) and causes of infertility were self-reported at baseline and biennial follow-up questionnaires., Main Outcome Measure(s): Cancer diagnosis was confirmed through medical record review and classified as obesity-related (colorectal, gallbladder, kidney, multiple myeloma, thyroid, pancreatic, esophageal, gastric, liver, endometrial, ovarian, and postmenopausal breast) or non-obesity-related (all other cancers). We fit the Cox proportional-hazards models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between infertility and cancer incidence., Result(s): During 2,149,385 person-years of follow-up, 26,208 women reported a history of infertility, and we documented 6,925 incident invasive cancer cases. After adjusting for body mass index and other risk factors, women who reported infertility had a higher risk of developing cancer than gravid women without a history of infertility (HR, 1.07; 95% CI, 1.02-1.13). This association was stronger among obesity-related cancers (HR, 1.13; 95% CI, 1.05-1.22; vs. non-obesity-related cancers, HR, 0.98; 95% CI, 0.91-1.06) and, in particular, obesity-related reproductive cancers (postmenopausal breast, endometrial, and ovarian cancers; HR, 1.17; 95% CI, 1.06-1.29) and was stronger among women who first reported infertility earlier in life (≤25 years, HR, 1.19; 95% CI, 1.07-1.33; 26-30 years, HR, 1.11; 95% CI, 0.99-1.25; >30 years, HR, 1.07; 95% CI, 0.94-1.22; P trend < .001)., Conclusion(s): A history of infertility may be associated with the risk of developing obesity-related reproductive cancers; further study is needed to elucidate the underlying mechanisms., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To update the American Society of Clinical Oncology guideline on the management of anxiety and depression in adult cancer survivors., Methods: A multidisciplinary expert panel convened to update the guideline. A systematic review of evidence published from 2013-2021 was conducted., Results: The evidence base consisted of 17 systematic reviews ± meta analyses (nine for psychosocial interventions, four for physical exercise, three for mindfulness-based stress reduction [MBSR], and one for pharmacologic interventions), and an additional 44 randomized controlled trials. Psychological, educational, and psychosocial interventions led to improvements in depression and anxiety. Evidence for pharmacologic management of depression and anxiety in cancer survivors was inconsistent. The lack of inclusion of survivors from minoritized groups was noted and identified as an important consideration to provide high-quality care for ethnic minority populations., Recommendations: It is recommended to use a stepped-care model, that is, provide the most effective and least resource-intensive intervention based on symptom severity. All oncology patients should be offered education regarding depression and anxiety. For patients with moderate symptoms of depression, clinicians should offer cognitive behavior therapy (CBT), behavioral activation (BA), MBSR, structured physical activity, or empirically supported psychosocial interventions. For patients with moderate symptoms of anxiety, clinicians should offer CBT, BA, structured physical activity, acceptance and commitment therapy, or psychosocial interventions. For patients with severe symptoms of depression or anxiety, clinicians should offer cognitive therapy, BA, CBT, MBSR, or interpersonal therapy. Treating clinicians may offer a pharmacologic regimen for depression or anxiety for patients who do not have access to first-line treatment, prefer pharmacotherapy, have previously responded well to pharmacotherapy, or have not improved following first-line psychological or behavioral management.Additional information is available at www.asco.org/survivorship-guidelines.

Background: Premenopausal women diagnosed with breast cancer often face aggressive chemotherapy resulting in infertility. Tamoxifen (TAM) is a selective estrogen receptor modulator that was previously suggested as a protective agent against chemotherapy-induced ovarian failure. In the current study, we examined mechanisms of the protective action of TAM in the ovaries of tumor-bearing rats treated with the chemotherapy drug cyclophosphamide (CPA)., Results: TAM prevented CPA-induced loss of ovarian follicular reserves. The protective TAM effect in the rat ovary partially resulted from decreased apoptosis. In addition, transcriptomic and proteomic screening also implicated the importance of DNA repair pathways as well as cell adhesion and extracellular matrix remodeling in the protective ovarian actions of TAM., Conclusions: Tamoxifen shielded the ovary from the side effects of chemotherapy without lessening the tumoricidal actions of mammary cancer treatment., (© 2023. The Author(s).)

Context: Many cancer survivors experience a lingering symptom burden after chemotherapy., Objectives: In this sequential multiple assignment randomized trial, we tested optimal sequencing of two evidence-based interventions for symptom management., Methods: Survivors of solid tumors (N = 451) were interviewed at baseline and stratified as high or low need for symptom management based on comorbidity and depressive symptoms. High need survivors were randomized initially to the 12-week Symptom Management and Survivorship Handbook (SMSH, N = 282) or 12-week SMSH with eight weeks of Telephone Interpersonal Counseling (TIPC, N = 93) added during weeks one to eight. After four weeks of the SMSH alone, non-responders on depression were re-randomized to continue with SMSH alone (N = 30) or add TIPC (N = 31). Severity of depression and summed severity index of 17 other symptoms over weeks one to13 were compared between randomized groups and among three dynamic treatment regimes (DTRs): 1) SMSH for 12 weeks; 2) SMSH for 12 weeks with eight weeks of TIPC from week one; 3) SMSH for four weeks followed by SMSH+TIPC for eight weeks if no response to the SMSH alone on depression at week four., Results: There were no main effects for randomized arms or DTRs, but there was a significant interaction of trial arm with baseline depression favoring SMSH alone during weeks one to four in the first randomization and SMSH+TIPC in the second randomization., Conclusion: The SMSH may represent a simple effective option for symptom management, adding TIPC only when there is no response to SMSH alone for people with elevated depression and multiple co-morbidities., (Copyright © 2023 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

The foodborne pathogen Listeria monocytogenes generally infects immunocompromised individuals, such as cancer patients, more frequently and with higher morbidity and mortality than the general population. Because of the anticipated risk associated with L. monocytogenes and other pathogens in produce, immunocompromised individuals are often placed on neutropenic diets that exclude fresh produce, though these risks have not been quantified. Therefore, this study developed a data-driven risk model for listeriosis in cancer patients who consume ready-to-eat (RTE) salads, consisting of leafy greens, cucumbers, and tomatoes, as influenced by kitchen-scale treatments and storage practices. Monte Carlo simulations were used to model the risk of invasive listeriosis during one chemotherapy cycle. Refrigerating all salad components decreased the median risk by approximately one-half log. For refrigerated salads with no treatment, the predicted median risk was ≤ 4.3 × 10 -08 . When salad ingredients were surface blanched with greens rinsed, the predicted risk decreased to 5.4 × 10 -10 . Predicted risk was lowest (1.4 × 10 -13 ) for a blanched "salad" consisting of solely cucumbers and tomatoes. Interestingly, rinsing, as recommended by FDA, only decreased the median risk by 1 log. A sensitivity analysis revealed that the highly variable dose-response parameter k strongly influenced risk, indicating that reducing uncertainty in this variable may improve model accuracy. Overall, this study demonstrates that kitchen-scale pathogen reduction approaches have high risk reduction efficacy and could be considered as an alternative to diets that exclude produce when making risk management decisions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The human topoisomerase IB (hTopoIB) enzyme is a monomeric protein that relaxes the supercoils on double-stranded DNA by forming a covalent DNA/hTopoIB complex by introducing a nick on the DNA strand. Inhibition of hTopoIB results in cell death, which makes this protein a strong target for the treatment of various cancer types, including small-cell lung cancers and ovarian cancers. Camptothecin (CPT) and indenoisoquinoline (IQN) classes of compounds inhibit the hTopoIB activity by intercalating to nicked DNA pairs; however, these inhibitors show different preferences towards DNA bases when bound to the DNA/hTopoIB complex. Here, we investigated the affinities of CPT and one IQN derivative towards different DNA base pairs. The two inhibitors showed different stacking behaviors in the intercalation site and interaction pattern with binding pocket residues, indicating that they have different inhibition mechanisms in the binding pocket that affects the base-pair selectivity. The results obtained from this study are expected to guide researchers in designing gene-specific and more potent compounds to fight cancer through hTopoIB poisoning.