Statin as a therapeutic agent in gastroenterological cancer

Statins inhibit 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, and are widely used as an effective and safe approach handle hypercholesterolemia. The mevalonate pathway is a vital metabolic pathway that uses acetyl-CoA to generate isoprenoids and sterols that are crucial to tumor growth and progression. Multiple studies have indicated that statins improve patient prognosis in various carcinomas. Basic research on the mechanisms underlying the antitumor effects of statins is underway. The development of new anti-cancer drugs is progressing, but increasing medical costs from drug development have become a major obstacle. Readily available, inexpensive and well-tolerated drugs like statins have not yet been successfully repurposed for cancer treatment. Identifying the cancer patients that may benefit from statins is key to improved patient treatment. This review summarizes recent advances in statin research in cancer and suggests important considerations for the clinical use of statins to improve outcomes for cancer patients.     

Statistical controversies in clinical research: basket trials,umbrella trials,and other master protocols: a review and examples

In recent years, cancers once viewed as relatively homogeneous in terms of organ location and treatment strategy are now better understood to be increasingly heterogeneous across biomarker and genetically defined patient subgroups. This has produced a shift toward development of biomarker-targeted agents during a time when funding for cancer research has been limited; as a result, the need for improved operational efficiency in studying many agent-and-target combinations in parallel has emerged. Platform trials, basket trials, and umbrella trials are new approaches to clinical research driven by this need for enhanced efficiency in the modern era of increasingly specific cancer subpopulations and decreased resources to study treatments for individual cancer subtypes in a traditional way. In this review, we provide an overview of these new types of clinical trial designs, including discussions of motivation for their use, recommended terminology, examples, and challenges encountered in their application.     

Psycho-oncology: where have we been? Where are we going?

This article reviews the development of the subspeciality of psycho-oncology and its contributions to patient care, encouraging more attention to and research into the care of the total patient: the physical, psychological, social and spiritual aspects of care. The result is enhanced quality of life as the patient is studied in the domains of living that are important, extending across the continuum of care from diagnosis to palliative care. In addition, cancer prevention and early detection depends largely on changing attitudes and behaviours that put people at greater risk. This is an important area of research for psycho-oncologists. In the past two decades, research has contributed to our understanding of the psychological responses that accompany a cancer diagnosis. Oncologists better recognise psychological distress and psychiatric disorders such as anxiety, depression and delirium (in hospitalised patients) as frequent comorbid disorders. The development of valid assessment tools for the patients' self-report has been important. Increasingly, outcome measures in controlled trials of new therapies include quality of life, and no longer look at survival alone. The future will continue to bring new challenges to psycho-oncology as patients face new challenges in treatment. A major aim of the next century will be to bring this integrated approach to all patients in an affordable manner.     

Prehabilitation and Rehabilitation for Patients with Lung Cancer: A Review of Where we are Today

Lung cancer is the third most common type of cancer in the UK, with nearly 50 000 new cases diagnosed a year. Treatments for lung cancer have improved in recent years with the advent of new surgical and radiotherapy techniques and the increased use of immunotherapies. These advances have resulted in increasing numbers of patients surviving beyond the completion of their treatment. Lung cancer patients are now not dying from their cancer diagnosis, but from other co-existing pathologies. Lung cancer patients commonly present with multiple comorbidities. Mitigating the effects of poor lifestyles and changing behaviours may improve the efficacy of treatments, reduce side-effects and improve the quality of life for lung cancer patients. Published evidence supports the use of interventions to manage behavioural habits, to optimise the health of patients. There is no consensus as to what, when or how to embed these into the patient pathway. Supporting patients before, during and after their cancer treatments to increase activity, eat well and stop smoking have been seen to decrease side-effects and improve patient outcomes and wellbeing. The challenge is to provide a package of interventions that is acceptable to patients and fits within the patient pathway so as not to conflict with diagnostic and therapeutic activities. This article reviews where we are today with providing behavioural support to optimise the health of lung cancer patients undergoing treatment.     

Behavior and cancer prevention.

This paper reviews research on the effects of behavioral risk factors on cancer incidence, as well as behavioral interventions for cancer prevention. Risk factors discussed here--tobacco use, diet, physical activity, and obesity/energy balance--are all linked with cancer etiology, and effective behavioral interventions have been developed in all of these areas. The most effective interventions appear to incorporate various components; for example, including individual as well as family activities, and involving multiple community organizations in behavior-changing activities. Behavioral theories have guided the design of these interventions, providing support that certain influences on behavior, such as self-efficacy, problem-solving skills, and social support, are important regardless of the specific behavioral target. As illustrated by the recent lowered lung cancer incidence and mortality rates for men and women, behavior change is possible and effective in cancer prevention. Clinical guidelines have been established for behavioral aspects of treatments for smoking cessation, dietary guideline compliance, physical activity, and obesity reduction, and new tools for dissemination of effective intervention materials will be helpful in increasing their use. Documenting the cost-effectiveness of behavioral interventions, using new technology interventions, and building on translational research to tailor interventions to individuals offer considerable promise for the future.     

Internet health resources and the cancer patient

The last decade has witnessed an explosion of online information regarding cancer and healthcare. Accompanying this has been a large body of research analyzing the quality of this information, how patients perceive these data and how this affects the doctor-patient relationship. This report reviews this literature, summarizing the current state of internet health resources available to the cancer patient and identifying areas for future research. Studies indicate that there are considerable internet resources available to cancer patients and that patients are using these resources as secondary information sources. Specifically, studies indicate that 16-64% of patients are using the internet to obtain health information. For the most part, patients perceive the online information to be reliable but maintain a healthy degree of skepticism. Studies objectively evaluating cancer information on the internet indicate that there is reasonable quality, although the language level of many sites is higher than that of the average American, which may limit the utility of the websites. Finally, while there is widespread internet use by physicians, healthcare providers are skeptical of their patients' ability to use the internet and may even be somewhat threatened by it. In summary, while there is a fairly large literature on internet resources available to the cancer patient, more research is needed. Specifically, it is important to better understand how patients access health information online and their associated preferences so that we can improve cancer patient's access to high quality health information on the internet to facilitate decision-making and health outcomes.     

Clinical oncology—A new era

Rapid growth in biomedical research coupled with dramatic advancement in biotechnology has significantly improved our understanding of the molecular basis involving cancer development and progression. This improvement has led to the discovery of new molecular markers for cancer diagnosis and prognosis as well as new molecular targets for cancer treatment and intervention. Continuous emergence of some new developing area in molecular profiling, new therapeutic agents, tissue microenvironment and systems biology have made significant progress in clinical oncology. Clinical research and investigation that focus on these new developments have begun to show exciting results that indicate future promises in improving patient management and survival.     

Clinical Oncology- A New Era

Rapid growth in biomedical research coupled with dramatic advancement in biotechnology has signi fi cantly improved our understanding of the molecular basis involving cancer development and progression. This improvement has led to the discovery of new molecular markers for cancer diagnosis and prognosis as well as new molecular targets for cancer treatment and intervention. Continuous emergence of some new developing area in molecular profi ling, new therapeutic agents, tissue microenvironment and systems biology have made signifi cant progress in clinical oncology. Clinical research and investi-gation that focus on these new developments have begun to show exciting results that indicate future promises in improving patient management and survival.     

EGFR inhibitors in non-small cell lung cancer (NSCLC): the emerging role of the dual irreversible EGFR/HER2 inhibitor BIBW 2992

Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer and is associated with significant mortality and morbidity worldwide. Despite improvements in conventional treatment for NSCLC, survival remains poor and improvements in patient outcome are warranted. Over recent years, basic scientific research has dramatically increased our knowledge of the pathogenesis of lung cancer and allowed us to uncover and understand the cellular pathways involved in this process. This has led to the development of therapies to selectively target these pathways. Among these, the epidermal growth factor receptor (EGFR) tyrosine kinase family and related downstream pathways play a critical role in cancer development and over recent years have become a validated target in NSCLC. The development of monoclonal antibodies and first-generation tyrosine kinase inhibitors (TKIs) targeted towards EGFR has had a considerable impact on patient outcomes. However, despite dramatic and sustained responses and the discovery of specific patient subgroups that may derive clinical benefit, resistance to first-generation EGFR TKIs inevitably develops. A new generation of agents have been developed to provide superior potency of target inhibition and further individualize the treatment of NSCLC. This article reviews EGFR-targeted therapies currently available for use and undergoing clinical development for the treatment of NSCLC, specifically focusing on next generation agents including BIBW 2992, an irreversible dual inhibitor of EGFR and HER2 kinases.     

Dose intensity as a therapeutic strategy in breast cancer

The results of systemic treatment for primary and metastatic breast cancer have plateaued in the past decade. The majority of oncologists continue to use the same chemotherapy regimens and endocrine therapies that were available in the mid 1970s. In metastatic breast cancer, still only 60–70% of patients can be expected to achieve a remission, with only 10–20% of these being a complete remission, which is usually of short duration. Metastatic breast cancer remains incurable today. Obviously, new treatment strategies are needed. The development of new active drugs, or the development of innovative ways of giving old drugs, has been disappointing in breast cancer. Similarly, combining hormones with chemotherapy, or the use of various biologic response modifiers, has not resulted in a major advance. One strategy that is currently undergoing active research is increased dose intensity of chemotherapy. This can be achieved by delivering extremely high doses of cytotoxic chemotherapy followed by hematopoietic support. A second approach involves delivering lower doses, but on a more frequent schedule than conventional programs. Preliminary results from phase II evaluation of these programs demonstrate high complete response rates, relatively short response durations, and considerable toxicity. However, 10–20% of patients treated with these regimens remain in complete remission several years after treatment, providing optimism that this approach may be effective in some patients. Advances in hematopoietic support, including autologous bone marrow transplantation (ABMT), peripheral stem cell administration, and the use of hematopoietic growth factors, have reduced toxicity. This strategy is now ready for phase III randomized trials in metastatic breast cancer as well as in the high-risk adjuvant patient to determine if high-dose therapy offers a worthwhile advantage in patients with breast cancer.     

Cancer vaccines: moving beyond current paradigms.

The field of cancer vaccines is currently in an active state of preclinical and clinical investigations. Although no therapeutic cancer vaccine has to date been approved by the Food and Drug Administration, several new paradigms are emerging from recent clinical findings both in the use of combination therapy approaches and, perhaps more importantly, in clinical trial design and end point analyses. This article will review recent clinical trials involving several different cancer vaccines from which data are emerging contrasting classic "tumor response" (Response Evaluation Criteria in Solid Tumors) criteria with "patient response" in the manifestation of increased patient survival post-vaccine therapy. Also described are several strategies in which cancer vaccines can be exploited in combination with other agents and therapeutic modalities that are quite unique when compared with "conventional" combination therapies. This is most likely due to the phenomena that (a) cancer vaccines initiate a dynamic immune process that can be exploited in subsequent therapies and (b) both radiation and certain chemotherapeutic agents have been shown to alter the phenotype of tumor cells as to render them more susceptible to T-cell--mediated killing. Consequently, evidence is emerging from several studies in which patient cohorts who first receive a cancer vaccine (as contrasted with control cohorts) benefit clinically from subsequent therapies.     

Inaugural lecture. Nursing and the counter culture for cancer

The discourse surrounding cancer is that of warfare and of a militaristic endeavour aimed at helping those with the disease survive. The consequences of such a discourse have not previously been explored in detail; in particular the culture of the 'cancer clinic' has not been examined for how a battle mentality might effect the nature of care and treatment. This paper explores how the biomedical response to cancer and its treatment has established approaches which neglect the more day to day experiences of people living with the disease, and the suffering, disability and distress that it causes. A radical reconstruction of the culture surrounding cancer is called for, so that a new environment of care might be offered. This should be more participatory, collaborative and empowering of people with cancer and their families. It should also shift the dominant theme in cancer management from 'survival' to the here and now, and to the needs and problems people have. An argument is made for the contribution that nursing might make to such a reconstruction through developing new approaches to symptom and problem management, reorganising cancer services so that they are more supportive and patient focused, and through nursing research studies aimed at radically changing the process of research itself.     

Who Is a Cancer Survivor? A Systematic Review of Published Definitions

The term “cancer survivor” is commonly used by different persons, clinical institutions, academic bodies, and political organizations although it lacks of a unanimous and detailed definition. The objective of the study is to make a systematic review of published and proposed definitions of “cancer survivor.” Utilizing a systematic search strategy with different strings of “cancer survivor,” we searched the following databases: Medline (June 1975–June 2015), Scopus (all the years), Web of Science (all the years), Google Scholar (all the years), ERIC (all the years). This review suggests that there is not a unique definition of who is a “cancer survivor” and what is “cancer survivorship.” However, the most widely used definition sees cancer survivorship as a process that begins at the moment of diagnosis and continues through the balance of life. This definition highlights psychological and legal patient’s needs—as well as medical ones—to receive care and assistance from the beginning and, at the same time, it establishes valid criteria for making scientific and statistical sampling research. The extensive use of the term “cancer survivor” indicates that it is a significant term. This review has been written to outline the state of the art and it invites to reflect on a shared definition that could satisfy both clinical and research aspects. Implication for cancer survivors: this compendium of proposed definitions may improve communication among the many patients and patient organizations that use and work with this term.     

Providing psycho-social support by telephone: what is its potential in cancer patients?

This paper provides an overview of the use of supportive telephone interventions in cancer patients. The small number of studies that have been reported to date have demonstrated that such approaches are feasible and well accepted. Current telephone counselling programmes for cancer patients have utilized both one-to-one and group approaches. Given the promise of telephone interventions to provide assistance to patients who may not otherwise receive psycho-social care because of factors such as geographical isolation, physical limitations, or lack of comfort with face-to-face approaches, further development and evaluation of programmes in this area is critically needed. We identify priorities for future research, including determining the most effective ways to deliver telephone interventions, identifying patient groups in which they are most successful, and evaluating cost-effectiveness.     

Nutrition during and after cancer treatment: a guide for informed choices by cancer survivors

Many studies have been conducted about dietary interventions aimed at preventing cancer. The American Cancer Society has published guidelines on diet, nutrition and cancer prevention, which are updated periodically as new evidence emerges, and other groups, too, have issued statements or guidelines about nutritional strategies to prevent cancer. Much less is known, however, about optimal nutrition for cancer survivors. This report looks at the different phases of cancer survivorship, from active treatment to advanced disease, and presents existing evidence from which informed decisions can be made regarding dietary choices. Popular complementary and alternative methods related to dietary intervention are reviewed. Nutrition information is also provided according to common cancer sites. As this is an area that requires survivors and health care providers to communicate effectively, a special section on "frequently asked questions" is provided for use as a patient education handout.     

Lung cancer: New biological insights and recent therapeutic advances

Approximately 1.6 million new cases of lung cancer are diagnosed each year throughout the world. In many countries, the mortality related to lung cancer continues to rise. The outcomes for patients with all stages of lung cancer have improved in recent years. The use of systemic therapy in conjunction with local therapy has led to improved cure rates in both resectable and unresectable patient groups. For patients with advanced stage disease, modest but real improvements in overall survival and quality of life have been achieved with systemic chemotherapy. A major focus of research has been the development of molecularly targeted agents and the identification of biomarkers for patient selection. Patients with non-small cell lung cancer with mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain achieve response rates of greater than 70% and superior progression-free survival when treated with an EGFR tyrosine kinase inhibitor compared with standard chemotherapy. This has now emerged as the preferred therapeutic approach for the subset of patients with a mutation in exons 19 or 21 of the EGFR. Another promising targeted approach involves the use of an anaplastic lymphoma kinase (ALK) inhibitor in patients with a translocation involving the echinoderm microtubule-associated protein-like 4 (EML4) and -ALK genes. Finally, a paradigm shift in favor of maintenance therapy for patients with advanced stage disease has gained strength from recent data. All of these advances have been made possible by developing a greater understanding of the biology, the discovery of novel anticancer agents, and improved supportive care measures. This article reviews the major strides made in the treatment of lung cancer in the recent past.     

Quantitative prognostic indicators of peritoneal surface malignancy: carcinomatosis, sarcomatosis, and peritoneal mesothelioma

Quantitative prognostic indicators for carcinomatosis and sarcomatosis are essential in the management of peritoneal surface malignancy. This need is greatly accentuated as a new comprehensive therapeutic approach emerges. The assessment of tumor histopathology, prior surgical score, lesion size, and distribution (Gilly classification and peritoneal cancer index) and the completeness of cytoreduction scores are the tools that are currently in use. Although current assessments have greatly facilitated clinical research, more precise comparisons demand improved quantitation and greater precision. Preoperative and intraoperative assessment of peritoneal surface malignancy will improve patient selection. Now more than ever, postoperative distribution and volume assessments using noninvasive modalities are needed for follow-up.