Cancer treatment and research最新文献

In Chap. 2 , we illustrated the application of the expected utility theory (EUT) to rational decision-making when no further diagnostic testing is available. In this chapter, we apply regret theory to the decision problems discussed in Chap. 2 .

As outlined in the Preface (and Chap. 1 and other chapters), this book espoused two fundamental views. The first view consists of the proposal that the threshold model represents a method to address the Sorites paradox, which is a consequence of a relationship between scientific evidence (that exists on a continuum of credibility) and decision-making (that is categorical, yes/no exercises).

The science of prognostication is emerging as a vital part of providing goal concordant patient care. Historically, modern medicine has tended to shy away from approaching prognostication as a core clinical skill, and prognosis as something to be shared directly with the patient. In recent years however, the medical field's shift towards a focus on patient autonomy and more openness in matters regarding end of life has propelled the study of prognostication into a more essential component of patient centered care. This calls for more emphasis on teaching the science of prognosis and the skill of prognostication as a core part of modern medical education. The following chapter aims to delve into the science of prognostication, explore the methods of formulating a prognosis, and discuss issues surrounding the communication of prognosis.

Nurses are the largest group of health and social care professionals globally and they are central to the provision of palliative care.

Cancer and cardiovascular disease are the two major causes of morbidity and mortality in worldwide. Discovering new therapeutic agents for the management of breast cancer (BC) has increased the numbers of cancer survivors but with the risk of cardiovascular adverse events (CV-AEs). All drugs can potentially damage the cardiovascular system, with different types of clinical manifestations from ischemic myocardial disease to vasculitis, thrombosis or pericarditis. An early detection of CV-AEs guarantees an earlier treatment, which is associated with better outcomes. Cardio-oncology field enlarged its studies to improve prevention, monitoring and treatment of all cardiotoxic manifestations related to old or modern oncological agents. A multidisciplinary approach with a close partnership between oncologists and cardiologists is essential for an optimal management and therapeutic decision-making. The aim of this chapter is to review all types of cardiotoxic manifestations related to novel and old agents approved for treatment of BC patients including chemotherapy, anti-HER2 agents, cyclin-dependent kinase 4/6 inhibitors, PolyADP-ribose polymerase (PARP) inhibitors, antiangiogenic drugs and immunotherapy. We also focused our discussion on prevention, monitoring, treatment, and management of CV-AEs.

Identification of tumours that have homologous recombination deficiency (HRD) has become of increasing interest following the licensing of PARP inhibitors. Potential methods to assess HRD status include; clinical selection for platinum sensitive disease, mutational/methylation status, genomic scars/signature and functional RAD51 assays. Homologous recombination (HR) is a dynamic process with the potential to evolve over a disease course, particularly in relation to previous treatment. This is one of the major drawbacks of genomic scars/signatures, as they only demonstrate historic HR status. Functional HR assays have the benefit of giving a real time HR status readout and therefore have the potential for clearer identification of patients who may benefit from PARP inhibitors at that specific time point. However, the development of RAD51 foci assays ready for clinical practice has been challenging. Pre-clinical considerations have included; controlling for variation in tumour proliferation, tissue type and whether DNA damage induction is required. Furthermore, the assays require correlation with clinical outcomes, an understanding of how they complement current testing modalities and validation of test performance in large cohorts. Despite these challenges, given the profound benefit from PARP inhibitors seen in those with an HRD phenotype to date, the ongoing development and validation of these functional HR assays remains of high clinical importance.

Polymerase theta (POLθ) is the critical multi-domain enzyme in microhomology-mediated end-joining DNA double-stranded break repair. POLθ is expressed at low levels in normal tissue but is often overexpressed in cancers, especially in DNA repair deficient cancers, such as homologous-recombination cancers, rendering them exquisitely sensitive to POLθ inhibition secondary to synthetic lethality. Development of POLθ inhibitors is an active area of investigation with inhibitors of the N-terminal helicase domain or the C-terminal polymerase domain currently in clinical trial. Here, we review POLθ-mediated microhomology-mediated end-joining, the development of POLθ inhibitors, and the potential clinical uses of POLθ inhibitors.

There is no denying that many revolutions took place in the fight against cancer during the last decades. However, cancers have always managed to find new ways to challenge humankinds. Variable genomic epidemiology, socio-economic differences and limitations of widespread screening are the major concerns in cancer diagnosis and early treatment. A multidisciplinary approach is essentially to manage a cancer patient efficiently. Thoracic malignancies including lung cancers and pleural mesothelioma are accountable for little more than 11.6% of the global cancer burden [4]. Mesothelioma is one of the rare cancers, but concern is the incidences are increasing globally. However, the good news is first-line chemotherapy with the combination of immune checkpoints inhibitors (ICIs) in non-small cell lung cancer (NSCLC) and mesothelioma has showed promising respond and improved overall survival (OS) in pivotal clinical trials [10]. ICIs are commonly referred as immunotherapy are antigens on the cancer cells, and inhibitors are the antibodies produce by the T cell defence system. By inhibiting immune checkpoints, the cancer cells become visible to be identified as abnormal cells and attack by the body's defence system [17]. The programmed death receptor-1 (PD-1) and programmed death receptor ligand-1 (PD-L1) inhibitors are commonly used immune checkpoint blockers for anti-cancer treatment. PD-1/PD-L1 are proteins produced by immune cells and mimic by cancer cells that are implicated in inhibiting T cell response to regulate our immune system, which results tumour cells escaping the defence mechanism to achieve immune surveillance. Therefore, inhibiting immune checkpoints as well as monoclonal antibodies can lead to effective apoptosis of tumour cells [17]. Mesothelioma is an industrial disease caused by significant asbestos exposure. It is the cancer of the mesothelial tissue which presents in the lining of the mediastinum of pleura, pericardium and peritoneum, most commonly affected sites are pleura of the lung or chest wall lining [9] as route of asbestos exposure is inhalation. Calretinin is a calcium binding protein, typically over exposed in malignant mesotheliomas and the most useful marker even while initial changes take place [5]. On the other hand, Wilm's tumour 1 (WT-1) gene expression on the tumour cells can be related to prognosis as it can elicit immune response, thereby inhibit cell apoptosis. A systematic review and meta-analysis study conducted by Qi et al. has suggested that expression of WT-1 in a solid tumour is fatal however, it gives the tumour cell a feature of immune sensitivity which then acts positively towards the treatment with immunotherapy. Clinical significance of WT-1 oncogene in treatment is still hugely debatable and needs further attention [21]. Recently, Japan has reinstated Nivolumab in patients with chemo-refractory mesothelioma. According to NCCN guidelines, the salvage therapies include Pembrolizumab in PD-L1 pos

This communication model attempts to reconcile the unknowingness of death, with a deeper inner knowingness that supports End of Life patients in an empowered way, through a mindset that models both oneness and presence with the death and dying experience. Through 23 years of experienced EOL care, I feel it seems necessary to rethink the very one-dimensional idea of dying and to create a space for a multidimensional experience. This model of communication and perspective-taking, offers my patients an opportunity for a secure connection to their own inner resources of knowing how to die. As our bodies are each equipped in our own unique way to do it perfectly, as the return of self, from the experience of being. This communication model also includes perspectives and narratives that attempt to make communication and care in the EOL experience more effortless and intuitive for the provider. Further, the model explains and illustrates why perspectives matter, as they impact connection in the relationship of the provider to the patient and includes a multidimensional perspective to question our own perceptions of death as providers. This model also includes the theory of balance and harmony. As it relates to the relativity of the experience of self, through the connection of communication and perspectives, as the exchange of information that occurs in the relationship between providers and patients. This information as a model represents a new awareness approach in the field of EOL care. It's based on 23 years of EOL experience and is supported through research and a fundamental theory of our reality, which intuitively and logically approaches relativity in our human connection to our patients as providers.

This chapter surveys the range of different orientations toward decision-making, common clinical scenarios, and considerations to bear in mind when caring for culturally diverse patients at the end of life. While this chapter draws on the cultural competency literature, its primary goal is to articulate an approach to end-of-life care that is rooted in cultural humility and structural competency. Medical providers, as representatives of the social institution of medicine, have their own cultural values that often come into conflict with patients' cultural values, especially when patients and providers have different unspoken visions of the "good death," or when patients wish to receive interventions that their providers deem futile. In the final section of the chapter, we seek to move away from this confrontational paradigm by analyzing two case studies of decision-making across cultures in order to empower providers to engage in value-based shared decision-making and thereby achieve goal-concordant care.