David Collingridge

Protocols, probity, and publication

992 www.thelancet.com Vol 373 March 21, 2009 2 French Food Safety Agency. Report on salt: evaluation and recommendations. 2002. http://www.afssa.fr/Documents/NUT-Ra-Sel.pdf (accessed Aug 7, 2008). 3 National Academy of Medicine. Report on salt intake and blood pressure. 2004. http://www.academie-medecine.fr/Upload/anciens/rapports_165_ fi chier_lie.rtf (accessed Aug 7, 2008). 4 Fondation Sciences Citoyennes. Notes on the libel action brought against Pierre Meneton (PM) by the CSF. Feb 5, 2008. http://sciencescitoyennes. org/spip.php?article1669 (accessed Aug 7, 2008). 5 Alderman MH, Madhavan S, Cohen H, Sealey JE, Laragh JH. Low urinary sodium is associated with greater risk of mycardial infarction among treated hypertensive men. Hypertension 1995; 25: 1144–52. 6 de Wardener HE. Salt reduction and cardiovascular risk: the anatomy of a myth. J Hum Hypertens 1999; 13: 1–4. 7 Anon. Don’t be naive about the salt industry. Salt Skip News 2006; 140: 4. http://www.saltmatters.org/newsletters/N_L_140.pdf (accessed Aug 6, 2008).

Primary care and cancer: integration is key.

In high-income countries, years of systematic investment into health-care systems have fi nally begun to yield dividends. Populations of these countries are living longer, healthier lives. Cancer is, in many ways, one of the big success stories in terms of survivorship. Thanks to eff ective public awareness campaigns, interventionist screening policies, and improved treatments, diseases that were once stigmatised as a certain death sentence can now be cured, prevented, or managed as chronic conditions. But an increasing number of cancer survivors, an ageing population, and increasing prevalence of cancer and other non-communicable diseases bring their own challenges to health-care systems. Initiatives to tackle cancer are frequently specialist ones, with resources and recognition being given to secondary and tertiary care both for cure and for care of patients. However, this is to neglect the vital role of the primary care physician (PCP)—and there is now a growing appreciation for the importance of the PCP in all aspects of cancer care at the population level. This changing attitude can be seen in microcosm in the UK. In 2013, as part of clinical commissioning groups, groups of general practitioners (GPs) were given the power to buy services to fulfi l their local health-care needs. Thus, GPs in England now have the power to plan and buy cancer services for the areas that they serve. Further to this, the National Institute for Health and Care Excellence (NICE) recently issued updated GP referral guidelines for suspected cancers. In the introduction to their recommendations, NICE highlighted the importance of early diagnosis in treating or curing cancer. As the fi rst entry point in many health-care systems for about half of all diagnosed cancers, accurate and early diagnosis by PCPs can improve survival outcomes. PCPs do not just improve the outcomes of patients with cancer through early diagnosis. Given their unique position within the health-care system, they can provide holistic medical care, taking into account the needs of patients and their families. They are also integral to care of the increasing numbers of cancer survivors; after being discharged from specialist care, it is the PCP that survivors turn to with new symptoms for palliative care, or for mental health services. Further, it is the PCP who often coordinates end-of-life care. Thus, at every point in the journey that a patient with cancer must endure, the PCP is an integral part of the support, helping to navigate an otherwise complex and confusing system. This backdrop forms the basis of the Commission we publish today. To capitalise on the unique strengths of primary care, there needs to be better integration of health-care systems between primary, secondary, and tertiary care. Integration of PCPs into secondary care will improve continuity of care that is currently poor—and to create a health-care system that truly serves the patient’s immersive needs rather than forcing patients to adapt to a system. The Commission is deliberately focused on countries with universal health-care systems, because it is these countries that are most amenable for integration. Nonetheless, the Commission’s fi ndings have implications for health-care systems worldwide, as detailed in the accompanying linked Comments. PCPs have a unique and diffi cult job—it is not easy to be a specialised generalist, and to pick out malignant symptoms, which are perhaps only seen a few times a year in an average primary care practice, from the many conditions seen every day. Through supporting and acknowledging the work that they do, PCPs can continue to provide crucial early diagnosis and the care that patients with cancer, and those who survive it, need. The NICE guidelines came with calls for further research into primary care and cancer, to which we fully agree: more high-level, practice-changing evidence of how health-care systems can better integrate between all levels is essential to ensure we create health-care systems that better serve patients’ needs in a more eff ective and coordinated way.

Three countries—half of the global cancer burden

Cancer control is a deceptively simple phrase. Just two words. But, its meaning yields entire textbooks of prose. Over the past 3 years, The Lancet Oncology has been investigating the drivers of cancer control via a series of Commissions. The fi rst in 2011, 1 addressed how the provision of adequate cancer care is aff ected by the cost of service delivery and considered the unsustainability of current models. The second, in 2013, 2 covered the broader issues that aff ect disease prevalence and containment— including political, social, and biological determinants— within the context of Latin America and, in particular, the powerhouse BRIC nation of Brazil. In this issue, we present the third instalment in this series of Commissions, 3 which builds on the issues raised in the previous reports and extends the debate to the other BRIC nations—namely Russia, India, and China. Collectively, these countries cover about 40% of the world’s population, experience 46% of all new cancers worldwide, and account for 52% of cancer deaths globally; but on the basis of national wealth, the World Bank ranks them just 45th, 127th, and, 92nd, respectively, indicating a sizable gap between disease burden and ability to aff ord eff ective control measures. Additionally, these countries face considerable and unique sociopolitical, cultural, and environmental factors that add extra layers of complexity to the challenges that lie ahead and to their ability to enact change.

The intersection of global health with cancer control.

Despite major advances in care, global cancer mortality is rising steadily, and disproportionately in low-income and middle-income countries. Through past Commissions and Series, The Lancet Oncology has steadily charted this worrying trend and issued multiple calls for action. Our concern is not limited simply to the human cost of cancer: rising cancer incidence carries a very real economic price, both in terms of costs sunk into health care and, given the increasing emergence in patients of working age, in terms of widening inequalities and reducing countries’ economic output. We are by no means alone in highlighting what rising incidence of cancer means for the world. Indeed, in 2011, the UN issued a resolution explicitly stating that the rising burden of non-communicable disease “constitutes one of the major challenges for development in the twentyfi rst century, which undermines social and economic development throughout the world and threatens the achievement of internationally agreed development goals”. Unfortunately, the world appears unprepared to meet the challenge. Only this year, for example, did WHO add basic chemotherapy drugs to its list of essential medicines. Radiotherapy is uniquely placed to deliver highly eff ective curative and palliative care for patients with cancer, often in a way in which other modalities cannot. Moreover, radiotherapy is more scalable and multifunctional than any other treatment modality. Yet, the world’s capacity for radiotherapy is unacceptably low in view of the high burden of disease, and insuffi ciency exists even in very-high-income countries. The invest ment need, from a health-care perspective, is clear. However, we do not live in a perfect world where all costs and needs are created equally, and competing demands and politics create uneven pressures on fi nite budgets. Although it has been previously assumed that radiotherapy is the most cost-eff ective treatment for cancer treatment, hard evidence has been lacking. The Commission published in this issue now presents convincingly the economic case. In 2013, the Union for International Cancer Control (UICC) created the Global Task Force on Radiotherapy for Cancer Control (GTFRCC) to address the central role of radiotherapy in cancer treatment. In one of the linked Comments, the leaders of the GTFRCC explain in greater detail the rationale for taskforce’s inception. With more than 100 members from 30 countries, more than 2 years of work have now quantifi ed the need, cost, and economic benefi t of worldwide investment in radiotherapy. Given the scale of ambition outlined in the Commission and the associated time horizon, it is imperative that the work begun by the Commissioners continues to reverberate throughout future generations. To that end, the GTFRCC also set up a Young Leaders Programme that includes young radiotherapists, oncologists, and other medical professionals at the beginning of their careers who are dedicated to global health and continuing the work of advocating accessible radiotherapy worldwide. Too often, calls for the rising tide of cancer incidence to be checked are made with earnest intentions but soft hearts. The evidence presented in this Commission from a global body of experts provides a rational economic case to begin radiotherapy investment worldwide. The time for circular discussion and argument is over; the time for action is now.

Multidisciplinary Head and Neck Cancer Symposium

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Neuro-oncology: a call for papers

Despite considerable research and the introduction of new therapies, long-term positive outcomes for patients with brain tumours are rare, and most patients experience a recurrence or progression of their cancer irrespective of the intervention. Consequently, mortality is high and many patients have neurological morbidity during the course of their disease. The Lancet Neurology and The Lancet Oncology are therefore issuing a joint call for papers that address cancers of the CNS. We are specifi cally interested in the results of randomised controlled trials and other original clinical studies that will have a profound eff ect on clinical practice, or on the fundamental understanding of tumour or CNS biology, or on the management of neurological sequelae. Accepted papers will be published in either The Lancet Neurology or The Lancet Oncology, and publication will coincide with the quadrennial meeting of the World Federation of Neuro-oncology and 6th meeting of the Asian Society for Neuro-oncology (WFNO/ASNO), to be held in Yokohama, Japan, on May 11–14, 2009. We are especially interested in research that will be presented at this conference, but we will also consider other suitable articles. If your submission describes, in part or wholly, a study accepted for presentation at the WFNO/ASNO meeting, please let us know the precise details of the type of presentation (such as poster or oral presentation), including dates and times, so that publication can be scheduled to comply with WFNO/ ASNO embargo policies. Articles can be submitted via either The Lancet Neurology’s or The Lancet Oncology’s online submission services, but all authors must clearly state in the covering letter that their submission is in response to the TLN/TLO call for papers. The closing date for this call for papers is March 13, 2009.

World Cancer Declaration: a need for partnership

In the September issue of The Lancet Oncology, Franco Cavalli outlined the revised World Cancer Declaration. This declaration—a central objective of the International Union Against Cancer (UICC)—outlines 11 targets that must be tackled if the global cancer burden is to be decreased substantially. Cancer health-care providers and advocates have long-forewarned of an impending cancer epidemic. This message has often fallen on deaf ears outside of health communities; indeed, it has often been under-appreciated even in other health specialties. This apocalyptic vision of the future, however, is not an exercise in melodramatics; the stark truth is cancer kills more people than tuberculosis, malaria, and AIDs combined, and over two-thirds of all deaths occur in low-to-middle income countries where resources are scant or non-existent. Depressingly, most of these deaths are needless: if the knowledge and options available today were exploited to their maximum eff ect, most cancers could be avoided or cured. If the World Cancer Declaration is to have demonstrable eff ects, the UICC can not be expected to work in isolation. The declaration needs to be adopted by governments, health authorities, non-governmental organisations, philanthropic organisations, and other involved parties worldwide. The WHO, in particular, has a large part to play and must reverse the silence that has come out of its departments for far too long on cancer control. The World Cancer Declaration is an ambitious affi rmation that needs to resonate with an intensity far greater than that achieved with the Framework Convention on Tobacco Control—the only notable success story up to now in implementing a global public-health policy with potential to decrease the cancer burden. The eff ect of cancer diff uses across all aspects of humanity. The consequences of this disease are not restricted to just the acute treatment needs within a health-care system. Governments need to provide a unifi ed strategy that shapes policies, not just in health, but also in economics; trade and industry; innovation; education; employment; transportation; food and the environment; communities and local government; culture, media, and sports; international aff airs; and justice. The compartmentalised debates that permeate politics about how resources and infrastructure are allocated need to end, and wide-ranging positive actions taken. We can no longer aff ord to sit on our hands and watch people die needlessly. We all have a personal and common responsibility to help overcome this global challenge and I encourage you to read the World Cancer Declaration, endorse the policy via the UICC website, and think carefully about what changes you can do, however small, in your private and professional lives to bring about change, before we live to regret this moment in history.

Treating head and neck cancer: for better or for worse?

Head and neck cancer is a heterogenous group of diseases arising from a range of anatomical sites with distinct histopathologies and an unpredictable presentation. Over half a million new cases are diagnosed globally each year, with the majority being of squamous cell origin arising from the mucosal lining of the oral cavity, oropharynx, larynx, and hypopharynx, and often related to tobacco and alcohol misuse. Although surgery and chemoradiotherapy remain the mainstay of treatment, these treatments can substantially impede quality of life by having detrimental functional and cosmetic outcomes. Recent research has therefore focused on trying to ameliorate treatment-induced toxic effects and improving morphological results. Such advances include new targeted approaches such as immunotherapy, stereo tactic radiotherapy, and intensity-modulated radiotherapy. Despite improvements, considerations such as functional outcomes, ability to tolerate treatment, organ preservation, and the influence of comorbidity, are a major challenge to the management of this disease. Any improvements, therefore, need to adequately translate into outcomes that are both clinically meaningful and do not decrease quality of life further (either functionally or psychologically). In this issue of The Lancet Oncology, we publish a Series of four papers focused on pertinent issues related to the management and treatment of patients with head and neck cancer. Sandro Porceddu and colleagues discuss the unique challenges present in the management of elderly patients with locoregionally defined head and neck cancer, and emphasise the importance of life expectancy, comorbidities, performance and functional status, social support, and patient preference. Nancy Lee and colleagues discuss the benefits of radiotherapy with protons rather than photons by showing how de-intensification and treatment personalisation can decrease morbidity, but at increased financial cost. Louis Harrison and colleagues discuss how the future of personalised radiotherapy treatment might be the use of genomic-adjusted radiation doses, which could reduce radiotherapy intensity to vital structures and better preserve voice and speech articulation, swallowing, vision, hearing, and salivation. Finally, Jonas Johnson and colleagues discuss palliative care options for patients with recurrent head and neck cancer, arguing that the use of aggressive, curative intent chemotherapy and radiotherapy is not always in line with patients’ end-of-life wants and needs. By shedding light on recent advances in the treatment and management of this disease, we hope that this Series will raise awareness on innovative and tailored approaches that will help broaden options for those patients who suffer from a disease in which, uniquely, well-intentioned medical interventions can often mutilate. In a future Series, we will examine other important considerations in this setting related to surgical advances, biomarker research, drug resistance, and novel drug development.

Cancer in Peru: a detailed examination

1300 www.thelancet.com/oncology Vol 18 October 2017 everolimus than among those receiving placebo. Pavel and colleagues reported that patients were more bothered by side-effects of everolimus than by those of placebo (mean score for this question was twice as high at week 8 and 5·7 times higher at week 48 in individuals assigned everolimus vs those allocated placebo). Thus, everolimus caused more side-effects, although this comparison should be interpreted according to the duration of treatment (twice as long with everolimus than with placebo). Thus, does this finding mean that, despite side-effects, the reason that no difference was noted in HRQOL was because everolimus is effective, but not sufficiently so to improve it? The second hypothesis is that we do not have good methods to assess small differences in HRQOL between treatments for NETs. Indeed, significant improvements of HRQOL have been reported when a treatment has a large effect by comparison with the control and in diseases with rapid clinical deterioration (eg, metastatic pancreatic adenocarcinoma). By contrast, it is much more difficult to show such an improvement in NETs, which usually have a more indolent natural history with fewer patients having symptoms at study inclusion. Indeed, we cannot expect improvement in HRQOL during everolimus treatment, particularly among patients with asymptomatic NETs who have excellent HRQOL without treatment and who, therefore, might be less willing to accept side-effects, even those of grade 1–2, after initiation of a long-term antitumour drug. It is of note that Pavel and colleagues used the FACT-G questionnaire, and in the sunitinib study, the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire was used, both of which were developed for cancer patients in general, and the HRQOL endpoint was assessed up until the time of drug discontinuation or shortly after. Questionnaires specifically developed for NETs—eg, the Norfolk quality of life tool or the EORTC QLQ-G.I.NET21— are available but are adapted for functional tumours. Therefore, new simple methods to assess HRQOL, which take into account the specificities of this disease, are needed, but in the meantime a longer term assessment of HRQOL of patients with NETs might provide some important insight into the effectiveness of treatment.

Cancer control in Latin America and the Caribbean: a bold ambition?

1The story in low-to-middle-income countries is even more stark. Cancer control is often a low priority when compared with the overriding need to tackle socioeconomic deprivation, war, crime, infectious disease, sanitation, housing, and education. And intertwined with these issues are cultural, religious, and philosophical attitudes towards society and medicine that infl uence the eff ectiveness of many initiatives. But despite this, eff orts must be made: 80% of the world’s burden of cancer is to be found in low-to-middle-income countries, and yet just 5% of the world’s fi nancial capacity is available to deal with the attendant problems. To reach the WHO target of reducing preventable deaths from noncommunicable diseases by 25% by 2025, far-reaching commitments are needed. The publication of the Stop Cancer Now! appeal, for example, highlights ten steps 2 that governments and policy makers can take to confront this challenge head-on. In this special issue of The Lancet Oncology, we publish