Efficacy and safety of anti-PD-1/PD-L1-based dual immunotherapies versus PD-1/PD-L1 inhibitor alone in patients with advanced solid tumor: a systematic review and meta-analysis.

INTRODUCTION: Numerous randomized controlled trials (RCTs) have investigated PD-1/PD-L1 inhibitor-based combination therapies. The debate surrounding the potential additive clinical benefits of combination of two immune-oncology (IO) therapies for cancer patients persists. METHODS: Both published and grey sources of randomized clinical trials that compared anti-PD-1/PD-L1-based immunotherapy combinations with monotherapy in patients with advanced or metastatic solid tumors were encompassed. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs). RESULTS: Our analysis encompassed 31 studies comprising 10,341 patients, which covered 12 distinct immune-oncology combination regimens. Across all patients, the immunotherapy combinations exhibited the capability to enhance the ORR (OR = 1.23 [95% CI 1.13-1.34]) and extend PFS (HR = 0.91 [95% CI 0.87-0.95]). However, the observed enhancement in OS (HR = 0.96 [95% CI 0.91-1.01]) was of no significance. Greater benefits in terms of PFS (HR = 0.82 [95% CI 0.72 to 0.93]) and OS (HR = 0.85 [95% CI 0.73 to 0.99]) may be particularly pronounced in cases where PD-L1 expression is negative. Notably, despite a heightened risk of any-grade TRAEs (OR = 1.72 [95% CI 1.40-2.11]) and grade greater than or equal to 3 TRAEs (OR = 2.01 [95% CI 1.67-2.43]), toxicity was generally manageable. CONCLUSIONS: This study suggests that incorporating an additional immunotherapy agent with PD-1/PD-L1 inhibitors can elevate the response rate and reduce the risk of disease progression, all while maintaining manageable toxicity. However, there remains a challenge in translating these primary clinical benefits into extended overall survival.

Targeted Molecular Imaging and Therapy Based on Nuclear and Optical Technologies.

Both nuclear and optical imaging are used for in vivo molecular imaging. Nuclear imaging displays superior quantitativity, and it permits imaging in deep tissues. Thus, this method is widely used clinically. Conversely, because of the low permeability of visible to near-IR light in living animals, it is difficult to visualize deep tissues via optical imaging. However, the light at these wavelengths has no ionizing effect, and it can be used without any restrictions in terms of location. Furthermore, optical signals can be controlled in vivo to accomplish target-specific imaging. Nuclear medicine and phototherapy have also evolved to permit targeted-specific imaging. In targeted nuclear therapy, beta emitters are conventionally used, but alpha emitters have received significant attention recently. Concerning phototherapy, photoimmunotherapy with near-IR light was approved in Japan in 2020. In this article, target-specific imaging and molecular targeted therapy utilizing nuclear medicine and optical technologies are discussed.

"Being ill was the easy part": exploring cancer survivors' reactions to perceived challenges in engaging with primary healthcare.

PURPOSE: Cancer survivors experience barriers to primary healthcare (PHC) services. The aim was to explore reactions to and opinions about perceived challenges associated with PHC access and quality among cancer survivors in Sweden, including how they have acted to adapt to challenges. METHODS: Five semi-structured focus group interviews were conducted with cancer survivors (n = 20) from Skåne, Sweden, diagnosed with breast, prostate, lung, or colorectal cancer or malignant melanoma. Focus groups were mixed in regard to diagnosis. Data were analysed using a descriptive template analysis approach. RESULTS: In light of perceived challenges associated with access to adequate PHC, participants experienced that they had been forced to work hard to achieve functioning PHC contacts. The demands for self-sufficiency were associated with negative feelings such as loneliness and worry. Participants believed that cancer survivors who lack the ability to express themselves, or sufficient drive, risk missing out on necessary care due to the necessity of being an active patient. CONCLUSIONS: The findings highlight negative patient experiences. They have implications for the organization of care for cancer survivors as they indicate a need for more efficient post-treatment coordination between cancer specialist care and PHC providers, as well as increased support for patients leaving primary cancer treatment.

Recent progress of iron-based nanomaterials in gene delivery and tumor gene therapy.

Gene therapy aims to modify or manipulate gene expression and change the biological characteristics of living cells to achieve the purpose of treating diseases. The safe, efficient, and stable expression of exogenous genes in cells is crucial for the success of gene therapy, which is closely related to the vectors used in gene therapy. Currently, gene therapy vectors are mainly divided into two categories: viral vectors and non-viral vectors. Viral vectors are widely used due to the advantages of persistent and stable expression, high transfection efficiency, but they also have certain issues such as infectivity, high immunological rejection, randomness of insertion mutation, carcinogenicity, and limited vector capacity. Non-viral vectors have the advantages of non-infectivity, controllable chemical structure, and unlimited vector capacity, but the transfection efficiency is low. With the rapid development of nanotechnology, the unique physicochemical properties of nanomaterials have attracted increasing attention in the field of drug and gene delivery. Among many nanomaterials, iron-based nanomaterials have attracted much attention due to their superior physicochemical properties, such as Fenton reaction, magnetic resonance imaging, magnetothermal therapy, photothermal therapy, gene delivery, magnetically-assisted drug delivery, cell and tissue targeting, and so on. In this paper, the research progress of iron-based nanomaterials in gene delivery and tumor gene therapy is reviewed, and the future application direction of iron-based nanomaterials is further prospected.

Adjuvants for cancer mRNA vaccines in the era of nanotechnology: strategies, applications, and future directions.

Research into mRNA vaccines is advancing rapidly, with proven efficacy against coronavirus disease 2019 and promising therapeutic potential against a variety of solid tumors. Adjuvants, critical components of mRNA vaccines, significantly enhance vaccine effectiveness and are integral to numerous mRNA vaccine formulations. However, the development and selection of adjuvant platforms are still in their nascent stages, and the mechanisms of many adjuvants remain poorly understood. Additionally, the immunostimulatory capabilities of certain novel drug delivery systems (DDS) challenge the traditional definition of adjuvants, suggesting that a revision of this concept is necessary. This review offers a comprehensive exploration of the mechanisms and applications of adjuvants and self-adjuvant DDS. It thoroughly addresses existing issues mentioned above and details three main challenges of immune-related adverse event, unclear mechanisms, and unsatisfactory outcomes in old age group in the design and practical application of cancer mRNA vaccine adjuvants. Ultimately, this review proposes three optimization strategies which consists of exploring the mechanisms of adjuvant, optimizing DDS, and improving route of administration to improve effectiveness and application of adjuvants and self-adjuvant DDS.

The BTLA-HVEM axis restricts CAR T cell efficacy in cancer.

The efficacy of T cell-based immunotherapies is limited by immunosuppressive pressures in the tumor microenvironment. Here we show a predominant role for the interaction between BTLA on effector T cells and HVEM (TNFRSF14) on immunosuppressive tumor microenvironment cells, namely regulatory T cells. High BTLA expression in chimeric antigen receptor (CAR) T cells correlated with poor clinical response to treatment. Therefore, we deleted BTLA in CAR T cells and show improved tumor control and persistence in models of lymphoma and solid malignancies. Mechanistically, BTLA inhibits CAR T cells via recruitment of tyrosine phosphatases SHP-1 and SHP-2, upon trans engagement with HVEM. BTLA knockout thus promotes CAR signaling and subsequently enhances effector function. Overall, these data indicate that the BTLA-HVEM axis is a crucial immune checkpoint in CAR T cell immunotherapy and warrants the use of strategies to overcome this barrier.

Commentary: importance of considering sex and gender when designing cancer care programs.

Due to perceived methodological complications, scientific studies have often excluded females. As a result, male-based findings have been generalized to females, despite physiological and biological differences between sexes. Gender has been even less considered in the literature, with little exploration specifically beyond traditional man/woman representation. This practice is compounded by a lack of what sex and gender encompass, including their erroneous use as synonyms. Sex- and gender-based differences, which are not clearly defined and recognized in scientific literature, are disregarded in health care delivery and, specifically relevant to the focus of this commentary, the development of cancer care programs. Conversely, accounting for sex- and gender in anti-cancer treatments and pathways can help create effective and personalized programming which could lead to an increased likelihood of adoption and adherence to treatment protocols. Although sex- and gender-specific programming may not be necessary in all situations, awareness of the concepts and possible impact on cancer care programs is paramount as more inclusive and personalized methodologies take shape. The goals of this commentary are to (a) clarify the terms sex and gender and (b) raise awareness of their applications and considerations for cancer care program design.

Implementation science and psycho-oncology: Advancing the translation of evidence into practice.

OBJECTIVES: This Special issue of Psycho-Oncology highlights examples of the application of implementation science to research in psycho-oncology. The aim is to demonstrate the different ways that implementation science is being used to generate evidence that can more readily translate evidence into changes in clinical practice. We hope this issue fosters greater interest in using the tools of implementation science to improve the lives of people affected by cancer. METHODS: The papers in the issue were selected from among those that responded to a call for submissions on the application of implementation science frameworks and methods to issues in psycho-oncology. The focus included but was not limited to research on: understanding barriers and facilitators of intervention/practice adoption; assessing implementation outcomes, evaluating implementation strategies, and improving behavioural and/or clinical outcomes. RESULTS: The 11 papers in this issue were grouped for presentation purposes into four common topics: barriers and facilitators to implementation; feasibility as a key implementation outcome; the design, selection and adaptation of implementation strategies; and building the foundation for psycho-oncology research translation via systematic reviews that focus on implementation strategy design. CONCLUSION: These papers demonstrate the breadth of current applications of implementation science to research in psycho-oncology. Alongside the studies featured in this issue, including cost-effectiveness analyses, tests of nationally-focused strategies and proactive planning for adaptation, we look forward to other innovations that will promote further growth of both disciplines to improve the integration of psycho-oncology interventions across healthcare systems.

Current evidence of integrative oncology modalities for managing adverse effects and survivorship issues among adolescents and young adult (AYA) cancer patients and survivors.

PURPOSE OF REVIEW: Symptom burden of cancer diagnosis and treatment has led adolescents and young adult cancer patients (AYAC) and survivors to seek different self-management strategies including integrative oncology (IO) modalities. IO holds great promise to improve survivorship issues in adolescents and young adult (AYA) cancer survivors. This review aims to encompass the current evidence of IO modalities and to analyze the efficacy of IO for managing survivorship issues among AYA cancer patients and survivors. RECENT FINDINGS: Nineteen randomized controlled trials included in this review evaluated mind and body modalities including both physical and psychological (74%) and psychological only (26%) modalities. Most assessed IO modalities were physical activity (PA) (37%) and structured exercise (10%). Most effective IO modalities found were PA, massage, mindfulness-based stress reduction (MBSR) and light therapy for treating AYA symptom burden. The Cochrane risk of bias (RoB-2) concluded 21% studies had high risk, 58% possessed some concerns and 21% had low risk. SUMMARY: Although evidence has shown that a number of IO modalities may improve survivorship among AYA cancer survivors, more rigorous study designs are needed in order for these modalities to be routinely recommended for use in clinical practice.

Supportive cancer care: is integrative oncology the future?

PURPOSE OF REVIEW: Nearly half of cancer patients use complementary therapies alongside the conventional cancer treatment. This clinical reality is a challenge for the medical team mainly to guarantee patient's safety. The evolution from Supportive Care to Integrative oncology is taking shape. RECENT FINDINGS: Integrative oncology, a new field in cancer care, combines conventional supportive care and validated complementary approaches. The first part of this review is to highlight the process of validation of one of the most popular complementary medicines among European cancer patients: homeopathy. It seems to be a well tolerated and useful complementary approach in integrative cancer care. The second part shows through the example of stage IV lung cancer the transition from conventional supportive care to integrative oncology with a benefit for their quality of life and survival. SUMMARY: The future of supportive cancer care seems to lead towards a move from coexistence of conventional care and complementary approaches to a combination of both in integrative oncology. This would require new skills among caregivers, specific academic training and adapted studies. Further research is needed to highlight the benefits in the specific field of integrative cancer care.

The role of specialist palliative care in individuals "living beyond cancer": a narrative review of the literature.

PURPOSE: Many patients living beyond cancer experience significant unmet needs, although few of these patients are currently reviewed by specialist palliative care teams (SPCTs). The aim of this narrative review was to explore the current and potential role of SPCTs in this cohort of patients. METHODS: A search strategy was developed for Medline, and adapted for Embase, CINAHL, and PsycInfo. Additionally, websites of leading oncology, cancer survivorship, and specialist palliative care organisations were examined. The focus of the search was on individuals living beyond cancer rather than other groups of cancer survivors. RESULTS: 111 articles were retrieved from the search for full text review, and 101 other sources of information were identified after hand searching the reference lists of the full text articles, and the aforesaid websites. The themes of the review encompass the definition of palliative care/specialist palliative care, current models of specialist palliative care, core activities of SPCTs, relevant expertise of SPCTs, and potential barriers to change in relation to extending their support and expertise to individuals living beyond cancer. The review identified a paucity of evidence to support the role of SPCTs in the management of patients living beyond cancer. CONCLUSIONS: Individuals living beyond cancer have many unmet needs, and specific services are required to manage these problems. Currently, there is limited evidence to support the role of specialist palliative care teams in the management of this cohort of people, and several potential barriers to greater involvement, including limited resources, and lack of relevant expertise.

Educating patients in a French cancer treatment center: How to ensure therapy safety while reckoning patients' knowledge and power to act.

In this article, we analyse how health professionals educate cancer patients to care for their condition and keep strict control over therapy safety. We study how much room for negotiation is left to patients during medical consultations so resources can still be exchanged. We pay particular attention to the trade of knowledge and powers between patients and doctors (power to act and to express oneself in an imbalanced relationship where knowledge is unequally shared). We opted for a qualitative approach with 41 interviews and several ethnological observations, first of consultations in haematology, then of pre-planned phone calls made to patients during the course of a cancer therapy follow-up scheme. The declared ambition of turning cancer patients into self-responsible patients actually re-enacts well-known procedures of control and knowledge acquisition aimed at narrowing their margin of manoeuvre for the sake of therapy safety. Even if some freedom is conceded, patients remain under the control of their medical hierarchy. Health professionals privilege two methods to keep control over patients and teach them therapy safety procedures. Which method is chosen, and how it is used, is dictated by the relationship between socially-diverse patients and health professionals. In the end, what the patient learns and the amount of control the doctor keeps over this process will depend on the distribution of power and knowledge among them, but asymmetry will always remain.

Reassessing granzyme B: unveiling perforin-independent versatility in immune responses and therapeutic potentials.

The pivotal role of Granzyme B (GzmB) in immune responses, initially tied to cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, has extended across diverse cell types and disease models. A number of studies have challenged conventional notions, revealing GzmB activity beyond apoptosis, impacting autoimmune diseases, inflammatory disorders, cancer, and neurotoxicity. Notably, the diverse functions of GzmB unfold through Perforin-dependent and Perforin-independent mechanisms, offering clinical implications and therapeutic insights. This review underscores the multifaceted roles of GzmB, spanning immunological and pathological contexts, which call for further investigations to pave the way for innovative targeted therapies.

Healthcare professional perspectives following implementation of an infection management care pathway for pediatric patients with cancer: a qualitative study.

PURPOSE: The Pediatric Oncology Group of Ontario (POGO) supported an effort to implement infection management care pathways based on clinical practice guidelines, to improve the consistency of infection management in pediatric cancer patients. The objective of this qualitative study was to describe the perspective of healthcare professionals (HCPs) following implementation. METHODS: Four tertiary pediatric oncology centers in Ontario, Canada, implemented the pathways. We randomly identified three HCPs per group (clinical pharmacists; nurse case managers, educators or practitioners and physician assistants; pediatric oncology fellows; or pediatric oncology staff physicians) per site and invited them to participate in a qualitative interview. One-on-one interviews were conducted remotely, followed by thematic analysis of interview transcripts. RESULTS: A total of 66 invitations were extended and 42 HCPs participated. Identified themes were: (1) implementation approach, (2) access and navigation, (3) engagement, (4) concerns, (5) workplace benefits, (6) reception, and (7) provincial harmonization. HCPs preferred in-person implementation strategies over e-mail communication. They identified teaching/educational utility and benefits to non-oncology departments and non-tertiary centers participating in shared care of patients. Other positive aspects related to evidence-based practice, safety, supporting oncology HCPs, and benefits to patients and families. Concerns included need to ensure users applied clinical judgement and loss of autonomy. Provincial harmonization of practice was viewed positively, although potential logistical and institutional cultural barriers were raised. CONCLUSIONS: Following infection management care pathway implementation, HCPs described educational utility and benefits to non-oncology departments, oncology HCPs, patients, and families. Our findings may facilitate future infection management care pathway provincial harmonization.

Aerobic glycolysis of vascular endothelial cells: a novel perspective in cancer therapy.

Vascular endothelial cells (ECs) are monolayers of cells arranged in the inner walls of blood vessels. Under normal physiological conditions, ECs play an essential role in angiogenesis, homeostasis and immune response. Emerging evidence suggests that abnormalities in EC metabolism, especially aerobic glycolysis, are associated with the initiation and progression of various diseases, including multiple cancers. In this review, we discuss the differences in aerobic glycolysis of vascular ECs under normal and pathological conditions, focusing on the recent research progress of aerobic glycolysis in tumor vascular ECs and potential strategies for cancer therapy.

Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets.

Metastasis remains the principal cause of cancer-related lethality despite advancements in cancer treatment. Dysfunctional epigenetic alterations are crucial in the metastatic cascade. Among these, super-enhancers (SEs), emerging as new epigenetic regulators, consist of large clusters of regulatory elements that drive the high-level expression of genes essential for the oncogenic process, upon which cancer cells develop a profound dependency. These SE-driven oncogenes play an important role in regulating various facets of metastasis, including the promotion of tumor proliferation in primary and distal metastatic organs, facilitating cellular migration and invasion into the vasculature, triggering epithelial-mesenchymal transition, enhancing cancer stem cell-like properties, circumventing immune detection, and adapting to the heterogeneity of metastatic niches. This heavy reliance on SE-mediated transcription delineates a vulnerable target for therapeutic intervention in cancer cells. In this article, we review current insights into the characteristics, identification methodologies, formation, and activation mechanisms of SEs. We also elaborate the oncogenic roles and regulatory functions of SEs in the context of cancer metastasis. Ultimately, we discuss the potential of SEs as novel therapeutic targets and their implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.

Cancer stigma: the need for policy and programmatic action.

Cancer is a stigmatized disease in many countries that impacts the quality of life and mental health of people affected by cancer. This commentary examines some dimensions of cancer stigma and has been developed based on insights from participants in a Union for International Cancer Control program dedicated to cancer patient organizations in low- and middle-income countries. Aimed at program managers and policy makers, this commentary highlights the importance of developing strategies to reduce cancer stigma in cancer control programs in different contexts, working closely with community-based civil society organizations and those with lived experience of cancer to understand, evaluate, and take action regarding the impact of cancer stigma on health-seeking behavior and patients' quality of life.