Showing papers in "Lancet Oncology in 2001"

Global cancer statistics in the year 2000

Abstract: Summary Estimation of the burden of cancer in terms of incidence, mortality, and prevalence is a first step to appreciating appropriate control measures in a global context. The latest results of such an exercise, based on the most recent available international data, show that there were 10 million new cases, 6 million deaths, and 22 million people living with cancer in 2000. The most common cancers in terms of new cases were lung (1.2 million), breast (1.05 million), colorectal (945 000), stomach (876 000), and liver (564 000). The profile varies greatly in different populations, and the evidence suggests that this variation is mainly a consequence of different lifestyle and environmental factors, which should be amenable to preventive interventions. World population growth and ageing imply a progressive increase in the cancer burden – 15 million new cases and 10 million new deaths are expected in 2020, even if current rates remain unchanged.

Epidemiology of breast cancer.

Abstract: Summary Breast cancer is the commonest cause of cancer death in women worldwide. Rates vary about five-fold around the world, but they are increasing in regions that until recently had low rates of the disease. Many of the established risk factors are linked to oestrogens. Risk is increased by early menarche, late menopause, and obesity in postmenopausal women, and prospective studies have shown that high concentrations of endogenous oestradiol are associated with an increase in risk. Childbearing reduces risk, with greater protection for early first birth and a larger number of births; breastfeeding probably has a protective effect. Both oral contraceptives and hormonal therapy for menopause cause a small increase in breast-cancer risk, which appears to diminish once use stops. Alcohol increases risk, whereas physical activity is probably protective. Mutations in certain genes greatly increase breastcancer risk, but these account for a minority of cases.

Role of nitric oxide in carcinogenesis and tumour progression

Abstract: Summary Nitric oxide(NO) is a short-lived molecule required for many physiological functions, produced from Larginine by NO synthases (NOS). It is a free radical, producing many reactive intermediates that account for its bioactivity. Sustained induction of the inducible form of NOS (iNOS) in chronic inflammation may be mutagenic, through NO-mediated DNA damage or hindrance to DNA repair, and thus potentially carcinogenic. Expression of iNOS is positively associated with P53 mutation in tumours of the colon, lung, and oropharynx. Progression of a large majority of human and experimental tumours seems to be stimulated by NO resulting from activation of iNOS or constitutive NOS, whereas inhibition is documented in others. This discrepancy is largely explained by differential sensitivity of tumour cells to NO-mediated cytostasis or apoptosis and clonal evolution of NO resistant and NO-dependent cells. P53 mutation or loss is one of many events linked with NO resistance and dependence. NO can stimulate tumour growth and metastasis by promoting migratory, invasive, and angiogenic abilities of tumour cells, which may also be triggered by activation of cyclo-oxygenase (COX)-2. Thus, selective inhibitors of NOS, COX, or both may have a therapeutic role in certain cancers.

Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer.

Abstract: Summary Understanding the mechanisms underlying carcinogenesis provides insights that are necessary for the development of therapeutic strategies to prevent cancer. Chemoprevention – the use of drugs or natural substances to inhibit carcinogenesis – is an important and rapidly evolving aspect of cancer research. We discuss evidence that cyclooxygenase 2 (COX 2), an inducible form of the enzyme, is a potential pharmacological target to prevent cancer. Key data implicating a causal relation between increased activity of COX 2 and carcinogenesis and possible mechanisms of action of COX 2 in this context are covered. Importantly, selective COX 2 inhibitors appear to be safe enough in human beings to allow large-scale clinical testing in healthy people. Several chemoprevention trials using selective COX 2 inhibitors are underway.

Esthesioneuroblastoma: a meta-analysis and review

Abstract: Our objective was to review recent developments in diagnosis, staging, and treatment of esthesioneuroblastoma (ENB). A meta-analysis of publications between 1990 and 2000 was carried out, and studies were classified according to their main subject: origin/aetiology of ENB, histopathological diagnosis, and treatment. Data so far point to the basal progenitor cells of the olfactory epithelium as the origin of ENB. Histopathological diagnosis remains difficult and is based on results of antigen expression detected through a panel of antibodies by immunohistochemistry. RT-PCR of HASH expression could be a specific marker of ENB. Overall and disease-free survival at 5 years averaged 45% (SD 22) and 41% (SD 21) in the studies included in the meta-analysis. Survival in Hyams' grades I-II was 56% (SD 20) compared with 25% (SD 20) in grades III-IV (odds ratio 6.2). In patients with metastases in cervical lymph nodes (on average 5% of the total) survival was 29%, compared with 64% for patients with N0 disease (odds ratio 5.1). Survival according to treatment modalities was 65% for surgery plus radiotherapy, 51% for radiotherapy and chemotherapy, 48% for surgery, 47% for surgery plus radiotherapy and chemotherapy, and 37% for radiotherapy alone. The histopathological grading according to Hyams and the presence of cervical lymph-node metastases emerged as prognostic factors. A combination of surgery and radiotherapy seems to be the optimum approach to treatment. The exact role of chemotherapy in treatment protocols is still unclear. The role of elective neck dissection is unclear.

Trends in biomarker research for cancer detection.

Abstract: A key challenge in cancer control and prevention is detection of the disease as early as possible, enabling effective interventions and therapies to contribute to reduction in mortality and morbidity. Biomarkers are important as molecular signposts of the physiological state of a cell at a specific time. Active genes, their respective protein products, and other organic chemicals made by the cell create these signposts. As a normal cell progresses through the complex process of transformation to a cancerous state, biomarkers could prove vital for the identification of early cancer and people at risk of developing cancer. We discuss current research into the genetic and molecular signatures of cells, including microsatellite instability, hypermethylation and single-nucleotide polymorphisms. The use of genomic and proteomic high-throughput technology platforms to facilitate detection of early cancer by means of biomarkers, and issues on the analysis, validation, and predictive value of biomarkers based on these technologies are also discussed. We report on recent advances in identifying sources of biomarkers that can be accessed by noninvasive techniques, such as buccal-cell isolates, as well as traditional sources such as serum or plasma. We also focus on the work of the Early Detection Research Network at the National Cancer Institute, harnessing expertise from leading national and international institutions, to identify and validate biomarkers for the detection of precancerous and cancerous cells in assessing risk of cancer. The network also has a role in linking discovery to process development, resulting in early detection tests and clinical assessment.

Repair of DNA interstrand crosslinks: molecular mechanisms and clinical relevance

Abstract: Summary Drugs that produce DNA interstrand crosslinks (ICLs), between the two complementary strands of the double helix, have an important role in chemotherapy regimens for cancer. Novel crosslinking agents, and targeting strategies involving DNA crosslinking agents, continue to be developed. The ability of cells to repair DNA ICLs is a critical determinant of sensitivity, and recent clinical studies indicate that DNA repair capacity is strongly implicated in both inherent tumour sensitivity and acquired drug resistance. A detailed understanding of the cellular mechanisms that act to eliminate these critical DNA lesions is clearly important. DNA ICLs present a complex challenge to DNA repair mechanisms because of the involvement of both DNA strands. It is now clear that cells from bacteria and yeast to mammals eliminate interstrand ICLs through the coordinated action of several DNA repair pathways. Recently, a model of ICL repair has been proposed, in which mammalian cells use novel excision repair reactions (requiring the XPF and ERCC1 proteins) to uncouple the crosslink. This is followed by a homologous recombination step to provide the genetic information needed to complete repair. This new knowledge may permit the development of screens for tumour response to crosslinking agents, and should also aid the design of more effective crosslinking agents that evade DNA repair. In addition, the proteins mediating the repair reactions represent potential targets for therapeutic intervention.

Dermoscopy of pigmented skin lesions--a valuable tool for early diagnosis of melanoma.

Abstract: Summary The clinical use of dermoscopy has uncovered a new and fascinating morphological dimension of pigmented skin lesions. Dermoscopy is a noninvasive diagnostic technique that links clinical dermatology and dermatopathology by enabling the visualisation of morphological features not seen by the naked eye. Close examination of pigmented skin lesions in this way increases the effectiveness of clinical diagnostic tools by providing new morphological criteria for distinguishing melanoma from other melanocytic and non-melanocytic pigmented skin lesions.

Clinical role of positron emission tomography in oncology.

Abstract: Summary Positron emission tomography (PET) is now in routine use in oncology, through the success of metabolic imaging, mainly with fluorodeoxyglucose (FDG). Clear benefit is obtained with FDG PET in the assessment of patients with recurrent or residual disease, especially colorectal cancer and lymphoma. Preoperative staging of non-small-cell lung cancer with FDG PET is of proven benefit. Staging and restaging of patients with melanoma of stage II or greater is useful, and FDG PET has also been successfully used to investigate single pulmonary nodules. Tumour grading has been assessed, especially in the brain, but an important and emerging indication is the evaluation of tumour response with PET. Rapid decline of FDG uptake has been observed in responsive cancers. Further advances are being made with other fluorine-18-labelled and generatorbased PET tracers, the only ones that can be used in units without dedicated cyclotrons.

Marine organisms as a source of new anticancer agents.

Abstract: Various active anticancer agents are derived from plants and terrestrial microorganisms. The isolation of C-nucleosides from the Caribbean sponge, Cryptotheca crypta, four decades ago, provided the basis for the synthesis of cytarabine, the first marinederived anticancer agent to be developed for clinical use. Cytarabine is currently used in the routine treatment of patients with leukaemia and lymphoma. Gemcitabine, one of its fluorinated derivatives, has also been approved for use in patients with pancreatic, breast, bladder, and non-small-cell lung cancer. Over the past decade, several new experimental anticancer agents derived from marine sources have entered preclinical and clinical trials. This field has expanded significantly as a result of improvements in the technology of deep-sea collection, extraction, and large-scale production through aquaculture and synthesis. In this paper, examples of marine-derived experimental agents that are currently undergoing preclinical and early clinical evaluation are briefly discussed. A summary of the available information on the results of phase I and II trials of agents such as aplidine, ecteinascidin-734 (ET-734), dolastatin 10 and bryostatin 1 is also presented.

Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications

Abstract: Summary Since the discovery that cancer development requires the growth of new blood vessels, many investigations have revealed the key molecules in the regulation of new vessel formation. One of the most important of these molecules is vascular endothelial growth factor (VEGF) – an endothelial-cell-specific mitogen and survival factor. VEGF also causes increased vascular permeability and recruits progenitor endothelial cells from the bone marrow. Clinical observations have confirmed that VEGF status is closely associated with the extent of neovascularisation and prognosis in many solid tumours. VEGF status is predictive of resistance to various treatments, including radiotherapy, chemotherapy, and endocrine therapy. Preliminary results also indicate that anti-VEGF treatment suppresses cancer progression without serious toxic effects. Various approaches for the control of cancers involving inhibition of the activity of VEGF are currently being investigated. This review considers the clinical implications of VEGF, particularly its prognostic, predictive, and therapeutic value.

Childhood acute lymphoblastic leukaemia – current status and future perspectives

Abstract: The current cure rate of 80% in childhood acute lymphoblastic leukaemia attests to the effectiveness of risk-directed therapy developed through well-designed clinical trials. In the past decade there have been remarkable advances in the definition of the molecular abnormalities involved in leukaemogenesis and drug resistance. These advances have led to the development of promising new therapeutic strategies, including agents targeted to the molecular lesions that cause leukaemia. The importance of host pharmacogenetics has also been recognised. Thus, genetic polymorphisms of certain enzymes have been linked with host susceptibility to the development of de novo leukaemia or therapy-related second cancers. Furthermore, recognition of inherited differences in the metabolism of antileukaemic agents has provided rational selection criteria for optimal drug dosages and scheduling. Treatment response assessed by measurements of submicroscopic leukaemia (minimal residual disease) has emerged as a powerful and independent prognostic indicator for gauging the intensity of therapy. Ultimately, treatment based on biological features of leukaemic cells, host genetics, and the amount of residual disease should improve cure rates further.

Pattern of malignant disorders in individuals with Down's syndrome

Abstract: The pattern of occurrence of malignant disorders in people with Down's syndrome (DS) is unique and may serve as a model in the search for leukaemogenic genes and tumour suppressor genes on chromosome 21, since the risk of leukaemia is higher in individuals with DS than in non-DS individuals. Acute lymphoblastic leukaemia in DS shares many of the clinical characteristics of the same malignancy in other patients, and with current intensive therapy the long-term survival is similar. Myelodysplastic syndrome and acute myeloid leukaemia have unique clinical characteristics in these patients and are best described as a single disorder, termed myeloid leukaemia of DS. When these patients are treated intensively, they show better survival rates than patients without DS. This may be related to increased expression of genes on chromosome 21 contributing to increased chemosensitivity. Chronic myeloid leukaemia and chronic lymphocytic leukaemia occur less often than expected. With the exception of an increased risk of retinoblastoma, germ-cell tumours, and perhaps lymphomas, the risk of developing solid tumours is lower in both children and adults. Breast cancer is almost absent, and the risk of a second malignant disease after treatment for leukaemia also appears to be decreased. Increased susceptibility to apoptosis in DS may result in cell death rather than malignant transformation after major cell injuries. This hypothesis would explain the decreased risk of both solid tumours and secondary cancers.

Metronomic scheduling: the future of chemotherapy?

Abstract: Summary Tumour endothelium is a new target for anticancer treatments. Proliferating endothelial cells from the tumour, even if qualitatively different from those of blood vessels in the normal tissue of origin, remain putatively normal and genetically stable cells. The results of recent experimental studies have suggested that frequent administration of certain cytotoxic agents at low doses (a tenth to a third of the maximum tolerated dose), known as ‘metronomic' chemotherapy, increases the antiangiogenic activity of the drugs. The effects of these metronomic schedules of cytotoxic agents may be further enhanced by concurrent administration of novel, selective, treatments that inhibit, at a molecular level, the processes of tumour formation and growth eg angiogenesis, growth factor pathways, and other signal transduction cascades. The need to treat patients for long periods also supports the use of metronomic scheduling for chemotherapy, to minimise toxicity and to target both proliferating tumour cells and endothelial cells. This review describes the experimental studies involving metronomic schedules of chemotherapy, alone and in combination with angiogenesis inhibitors, and suggests a new therapeutic anticancer paradigm for controlling cancer by long-term therapy, based on the development of combinations of metronomic cytotoxic agents with individually tailored compounds designed to target specific molecules.

Panax ginseng--a non-organ-specific cancer preventive?

Abstract: For the past 50 years, the main weapons in the war against cancer have been early detection and surgical removal, radiotherapy, chemotherapy, and attempts to develop gene therapy. However, the results so far are less than ideal. One strategy now is to switch from therapeutic approaches to prevention of cancer by improving lifestyle and by identifying effective natural products as chemopreventive agents. One promising candidate with cancer-preventive effects that are not specific to any organ is Panax ginseng C A Meyer, a herb with a long medicinal history. Its protective influence against cancer has been shown by extensive preclinical and epidemiological studies, but these effects need to be carefully investigated by scientific clinical trials focusing on the major cancer killers stomach, lung, liver, and colorectal cancer.

Angiogenesis: pathological, prognostic, and growth-factor pathways and their link to trial design and anticancer drugs.

Abstract: Summary Angiogenesis is essential for tumour growth, invasion, and metastasis. Tumour blood vessels show many differences from normal vessels and are not genetically unstable, so they form a potentially key area for therapy of all types of cancer including leukaemias. Here we review current knowledge on the multiple pathways controlling tumour angiogenesis and assess which are the most clinically relevant. We also review the clinical evidence that angiogenesis affects the behaviour of cancer. Retrospective studies on intratumoral vascularisation suggest that it is an independent prognostic factor that merits prospective validation. Also, the presence of vascular endothelial growth factor in high concentrations in primary cancers is associated with poor prognosis. Key targets for drug development, current clinical trials, and the problems of developing drugs that do not have direct cytotoxic effects are reviewed. Recommendations are made on organising and monitoring antiangiogenic trials.

Depression in cancer patients.

Abstract: Clinical depression is a relatively common, and yet frequently overlooked, source of suffering among patients with cancer. All patients who face a life-threatening diagnosis such as cancer experience a normal albeit painful emotional reaction, but a substantial minority will become clinically depressed. This article reviews some basic information that oncology practitioners may find helpful in identifying patients at risk of experiencing a major depression. A brief overview of the epidemiology, diagnostic criteria, screening approaches, and special issues, such as depression in the elderly, high-risk populations, and suicide is also provided.

Current and future developments in the use of temozolomide for the treatment of brain tumours

Abstract: Brain tumours comprise only 2% of all adult cancers, but they are among the most debilitating malignant diseases. Temozolomide, an alkylating agent that can be administered orally, has been approved for the treatment of recurrent malignant glioma on a daily schedule for 5-day cycles. Continuous administration schedules with a higher dose intensity are being explored, but an improvement in efficiency remains to be shown. The benefit from temozolomide given as a single agent in recurrent disease will be several weeks at best. This drug is therefore now undergoing clinical testing as neoadjuvant chemotherapy or with concomitant radiotherapy in patients with newly diagnosed glioma. Several phase I trials are investigating the combination of temozolomide with other agents active against brain tumours. This review briefly summarises the pharmacological background and clinical development of temozolomide and focuses on current and future clinical exploration of this drug for the treatment of brain tumours.

Minimal residual disease in leukaemia patients

Abstract: Because of developments in diagnosis of haemopoietic malignant diseases during the past two decades, routine and reliable identification of very low numbers of malignant cells, known as minimal residual disease (MRD), is now possible. Several large-scale studies have shown that monitoring of MRD in haemopoietic malignant disease predicts clinical outcome. In acute lymphoblastic leukaemia, MRD detection is useful for evaluating early response to treatment and consequently for improving stratification, including treatment reduction. In acute promyelocytic leukaemia and chronic myeloid leukaemia, MRD information at specific time points enables effective early treatment intervention. MRD monitoring is also possible in other leukaemia subtypes, but in these disorders the clinical value of MRD detection is not yet known.

Circadian chronotherapy for human cancers.

Abstract: Cell physiology is regulated by a 24-hour clock, consisting of interconnected molecular loops, involving at least nine genes. The cellular clock is coordinated by the suprachiasmatic nucleus, a hypothalamic pacemaker which also helps the organism to adjust to environmental cycles. This circadian organisation brings about predictable changes in the body's tolerance and tumour responsiveness to anticancer agents, and possibly also for cancer promotion or growth. The clinical relevance of the chronotherapy principle, ie treatment regimens based upon circadian rhythms, has been demonstrated in randomised, multicentre trials. Chronotherapeutic schedules have been used to document the safety and activity of oxaliplatin against metastatic colorectal cancer and have formed the basis for a new approach to the medicosurgical management of this disease, which achieved unprecedented long-term survival. The chronotherapy concept offers further promise for improving current cancer-treatment options, as well as for optimising the development of new anticancer or supportive agents.

Targeting tumour vasculature: the development of combretastatin A4

Abstract: Summary The requirement for neovascularisation to permit the development of solid tumours beyond a threshold size, has focused attention on the therapeutic potential of agents that prevent angiogenesis. The multistep nature of angiogenesis presents several targets for intervention, including the inhibition of the endothelial-cell migration or proliferation normally associated with developing vessels. Compounds that damage established tumour vasculature are also of potential clinical use. We review the development of one such antivascular drug, combretastatin A4. This tubulin-binding agent was originally isolated from an African shrub, Combretum caffrum . The disodium combretastatin A4 phosphate prodrug is currently undergoing phase I clinical trials in the UK and USA. This review assesses the in vitro and in vivo data for combretastatin and the prodrug, and the preliminary data that have emerged from the phase I clinical trials.

Positron emission tomography in the diagnosis and staging of lung cancer: a systematic, quantitative review

Abstract: Summary Lung cancer is the cause of 32% of all male cancer deaths and 25% of all female cancer deaths. Because the prognosis depends on early diagnosis and staging, continuous evaluation of the diagnostic tools available is important. The aim of this study was to assess the diagnostic value of dedicated positron emission tomography (PET) and gamma-camera PET in the diagnostic investigation of non-small-cell lung cancer (NSCLC). A systematic literature search was carried out in the MEDLINE and EMBASE databases and the Cochrane Controlled Trials Register. We identified 55 original works on the diagnostic performance of PET with fluorodeoxyglucose in the investigation of NSCLC. For diagnosis of NSCLC, the mean sensitivities and specificities were, respectively, 0·96 (SE 0·01) and 0·78 (0·03) for dedicated PET, and 0·92 (0·04) and 0·86 (0·04) for gamma-camera PET. In the mediastinal staging of NSCLC, the results were 0·83 (0·02) and 0·96 (0·01) for dedicated PET and 0·81 (0·04) and 0·95 (0·02) for gamma-camera PET. We conclude that dedicated PET could be a valuable tool in the diagnosis and staging of NSCLC. However, studies of populations with a lower prevalence of NSCLC are recommended.

Women and lung cancer: does oestrogen play a role?

Abstract: Summary Smoking-related disease remains a major public-health problem. Large numbers of women continue to smoke, and new smokers are almost as likely to be female as male. Lung cancer is still a largely incurable disease; annual lung-cancer mortality in women exceeds that of breast cancer, and lung cancer now accounts for 12% of all new female cancer cases. The results of several studies suggest that women are more susceptible than men to lung cancer and to conditions that predispose to this cancer, such as chronic obstructive pulmonary disease. There is still much controversy about whether there is an increased lung-cancer risk in women across all populations. Many epidemiological studies have been negative or equivocal when comparing male and female lung-cancer risk. This article is not intended to be a comprehensive review of all epidemiological studies, or of all possible lung-cancer risk factors. Lung-cancer incidence and risk in women are discussed, and evidence for possible mechanisms of increased female risk are presented, including the role of oestrogen in the development of lung cancer.

Apoptosis: implications of basic research for clinical oncology

Abstract: Recent studies have indicated a role for apoptosis in a variety of human diseases. Suppression of apoptosis contributes to carcinogenesis by several mechanisms, including facilitating the accumulation of gene mutations, permitting growth-factor-independent cell survival, promoting resistance to immune-based cytotoxicity, and allowing bypassing of cell-cycle checkpoints, which would normally induce apoptosis. Defects in apoptotic mechanisms also play an important part in resistance to chemotherapy and radiation. The core machinery of the cell death pathway can be reduced to a few critical types of proteins, which are well conserved across animal evolution. This review gives an update on the key players involved in apoptosis as well as an overview of the involvement of apoptosis in disease, and novel diagnostic and therapeutic options derived from the extensive basic research on this topic carried out over the last decade.

Cancer chemoprevention by dietary constituents: a tale of failure and promise.

Abstract: Although the results of clinical intervention trials of beta-carotene to prevent lung cancer, and of dietary augmentation with fibre or fruit and vegetables to reduce the occurrence of colonic polyps have so far been negative, a structured path for the development of diet-derived constituents as cancer chemopreventive agents is emerging. Putative agents are identified on the basis of epidemiological and preclinical mechanistic studies. Some examples of promising diet-derived chemopreventive agents are folate, curcumin, genistein, and tea catechins. Long-term supplementation of the diet with folate seems to lower the risk of colorectal cancer. Curcumin in the spice turmeric, genistein in soya, and catechins in tea have tumour-suppressing properties in rodent models of carcinogenesis, and they interfere with cellular processes involved in tumour promotion and progression. Kinases, telomerase, cyclooxygenase-2, triggers of apoptosis, and transcription factors AP1 and nuclear factor kappaB are among the cellular targets. The investigation of dietary constituents should follow a structured design, incorporating parallel preclinical studies of the food source and the isolated agent in terms of efficacy, toxicity, biological mechanisms, and pharmacokinetics. Either the food source or the isolated agent should be selected for further development on the basis of dose-efficacy and toxicity data. Pilot clinical trials on the pharmacokinetics and mechanism-based markers of efficacy of the selected intervention should precede phase I-III development in suitable populations.

Farnesyl transferase inhibitors: a novel targeted therapy for cancer

Abstract: Activating oncogenic mutations of the RAS gene are common in cancer, occurring in 30% of solid tumours in adults. Inhibitors of the enzyme farnesyl protein transferase prevent a key step in the post-translational processing of the RAS protein, and were developed initially as a therapeutic strategy to inhibit cell signalling in RAS-transformed cells. As more has been learnt about the biological effects of farnesyl transferase inhibitors on cancer cells, it has become increasingly clear that tumours without oncogenic RAS mutations may also be targets for farnesyl transferase inhibitor therapy. Encouraging results from phase I and II clinical trials have emerged, creating both enthusiasm and new challenges for the optimum clinical development of this important new class of anticancer drug.

Unconventional therapies for cancer and cancer-related symptoms

Abstract: Summary A significant proportion of cancer patients try unconventional therapies and many use ‘complementary' therapies, as adjuncts to mainstream care, for management of symptoms and to improve quality of life. A smaller proportion use ‘alternative' therapies, which are typically invasive, biologically active, and commonly promoted as replacements for, rather than adjuncts to, mainstream therapy. Many alternative therapies, including high-dose vitamin C, the Di Bella regimen, and laetrile have been shown not to be effective. For others, such as metabolic therapy, evidence is extremely limited. Conversely, most complementary therapies are well studied and of proven benefit. There is evidence from randomised trials supporting the value of hypnosis for cancer pain and nausea; relaxation therapy, music therapy, and massage for anxiety; and acupuncture for nausea. Such complementary therapies are increasingly provided at mainstream cancer centres.

Dealing with stress, burnout, and grief in the practice of oncology

Abstract: Summary There is a substantial amount of published work describing how to help patients and families deal with stress, grief, and loss, but there is much less advice available for clinicians dealing with similar issues. Working as an oncologist is inherently difficult, and racked by emotional and psychological traumas. However, it can also be tremendously rewarding. In this review, I discuss the extent of stress and burnout in the practice of oncology, its causes and manifestations, and strategies for overcoming it.

The role of the coagulation system in tumour angiogenesis

Abstract: Summary The coagulation system, which is activated in most cancer patients, has an important role in tumour biology. It may make a substantial contribution to tumour angiogenesis, which represents an imbalance in the normal mechanisms that allow organised healing after injury. The recently recognised, but steadily growing, knowledge of the relationship between the coagulation and angiogenesis pathways has research and clinical implications. Manipulation of these systems may minimise both the neoangiogenesis essential for tumour growth and associated thromboembolic complications. However, since surgery is the primary treatment for most cancers, the angiogenesis of wound healing and haemostatic competence must be maintained. In this article, we summarise the complex interactions between the coagulation system and the angiogenic process that occur in cancer growth. We focus upon the contributions of the vascular endothelium, platelets, and coagulation factors to the angiogenic process and explore the coagulation system as a therapeutic target.