WHAT IS THE FUTURE OF CANCER RESEARCH?

Françoise Meunier

What is the future of cancer research?
Clinical research challengesin Europe

Foreword by János Frühling

Académie royale de Belgique

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ISBN : 978-2-8031-0419-2

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Foreword

The work entitled ‘What is the future of cancer research? Clinical research challenges in Europe’ is perhaps, after taking a quick glance at the title, of interest to a wider audience than initially anticipated. This somewhat dense little volume full of important data with appropriate comments, is targeted to oncologists in the broad sense of the word, not just care givers, but also all those that are affected one way or another by this serious disease. In addition, one needs to also include economists and political decision makers at both the national and European levels without neglecting the pharmaceutical industry.

Historically, the EORTC, founded in 1962 by a group of European visionaries including Professors G. Mathé (France), H. Tagnon (Belgium), D. Van Bekkum (The Netherlands) and S. Garratini (Italy), has provided a unique platform for European cancer research. The initiative was initially based on several principles:

Bring Europe to an integration level similar to that of the United States for the treatment of cancer;

Obtain a critical mass of patients by gathering patients with cancer from several European countries with already well-established medical infrastructures so as to be able to draw valid conclusions concerning cancer treatments;

Attain a high level of scientific credibility for European cancer research with a special focus on excellent collaboration among institutions;

Be in a position to submit the research results to the scrutiny of a statistically valid analyses ‘of high resolution’ so as to assert the validity of the obtained results;

As an ultimate goal, to improve the management of cancer and related problems by increasing survival but also patient's quality of life;

Start significant fundraising to ensure the continuity of the EORTC so as to secure optimal treatments for both current as well as future patients.

When the organization was founded, research work was initially centralized in Belgium at the Bordet Institute. The Netherlands, Belgium, France and Germany were the first participating countries and formed the core of the EORTC. A data center managed by Dr. M. Stacquet was created to centralize data and manage the very first randomized studies. Professor Françoise Meunier, a Medical Doctor and PhD who received her degrees from the Université libre de Bruxelles, was ideally suited for the position of Director General thanks to her extensive experience in internal medicine and infectious diseases which affected patients with cancer. In addition, she had pursued research for two years in the United States at the Memorial Sloan Kettering Cancer Center, a very prestigious research institute, and with this exceptional background, she took charge of the EORTC in 1991.

Since then and during the last 23 years, the EORTC research facilities have evolved to keep pace with methodological advances and scientific requirements, and the size of the research staff has expanded with the increasing challenges of conducting high quality cancer clinical research.

From then on, the EORTC became more important, trials were conducted in additional European countries, and new scientific paths were opened that were of interest not only to the specific organ linked pathologies but also the therapeutic cancer disciplines included in the oncological activities. Scientific collaboration with the pharmaceutical industry increased facing the emergence of numerous potential new drugs that needed to be evaluated.

We live in a society facing tremendous economic changes, one where the position of healthcare and any medical activity must be constantly questioned so as to adapt to the reality of financial constraints that do not respect the borders of countries or continents. The solidarity concept leads to permanent changes endorsed by most of the medical communities.

However, in this context we are currently witnessing the emerging of a two-tier medicine even in western European countries and the current legal framework development of personalized medicine (whilst being extremely promising for cancer research) may in the long term generate unsolvable economic challenges if one has the aim to make everybody benefit from the best available treatments.

The European legal framework related to the regulation of applied clinical trials, not always the most welcome, has created a dangerous precedent that hopefully Europe will be able to overcome, and this, thanks to the ten years of relentless negotiations skillfully led by Professor Françoise Meunier among others, in order to reach harmonization among Member States.

Unfortunately a lot of challenges remain to be solved still at the level of oncological diseases treatments, notably all matters regarding the conduct of international clinical research and the establishment of biobanks, but also insurance coverage and relations with the pharmaceutical industry.

One must not forget that all EORTC clinical trial protocols are defined according to the strictest scientific conditions and that all results obtained and validated by a solid statistical methodology will bring practical and tangible results at patient level where the EORTC played a decisive role as catalyst and as an unique European scientific network with an independent clinical research infrastructure.

This book will guide each reader through this complex world of applied clinical cancer research whilst becoming familiar with the fabulous and successful saga of the founders of the EORTC.

Prof. J. Frühling

Honorary permanent Secretary of the Royal Belgian Academy of Medicine

Introduction

Epidemiological data

Cancer is an ancient disease. Contrary to what some people may think, it is not a disease that appeared in the 20th century! In fact, some tumors have been found on very ancient corpses, specifically mummies and prehistoric animals. Skulls identified and dated between 1800 and 1400 B.C. (the Bronze Age) have also exhibited bone tumors. In fact, Hippocrates (460 to 377 B.C.) described breast cancer quite well.

Today cancer is the second leading cause of mortality in Europe after cardio-vascular diseases. Approximately 3.500.000 new cases are diagnosed every year in Europe, and unfortunately 1.500.000 people will die of the disease on an annual basis. However, the chart below (Figure 1) describes the decrease in mortality per cancer in Europe (all types) and its evolution (based on 100.000 people) between 1970 and 2013.

Figure I

Source: Malvezzi M. et al., “European cancer mortality predictions for the year 2013”, Annals of oncology, 24 (3), 2013, p. 1-9.

On the basis of epidemiological data and incidence forecasts, Europe, including Belgium, must prepare to face the reality of more and more diagnoses of cancers. Incidence, which is to say the number of new cancer cases, will continue to increase due to a variety of reasons:

The incredible progress in early detection measures (mammograms, colonoscopy, PSA (Prostate Specific Antigen) testing, etc.);

Smoking, particularly in women (who started later than men);

Ageing of the population.

One should not underestimate the spectacular drop in childhood mortality (mainly due to infectious diseases) that occurred over the course of the 19th and 20th centuries, and there has been a significant decrease in adult death rates linked to causes other than cancer, such as traffic accidents, infectious diseases (pneumonia, tuberculosis, septicemia) as well as cardio vascular diseases and diabetes.

The called ‘Age Pyramid’ in Europe is changing, people are living longer, and the percentage of elderly people is increasing. Since 65% of new cancer cases are observed in patients of 65 years of age and above, the ageing of the population is largely responsible for an ever increasing number of new cancer cases. One should also bear in mind that the life expectancy nowadays has increased considerably from 55 years of age in 1900 to 80 years of age today. The late start of a smoking habit in women (after World War II) is linked to an increase of lung cancers in women when, paradoxically, the mortality linked to this type of cancer in men has steadily decreased following an earlier decrease in smoking in that gender.

Figure 2

Cancer incidence and mortality patterns in Europe (2012)

Source: J. Ferlay and al., “cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012”, European Journal of cancer, vol. 49, 2013, p. 1374-1403.

In Belgium, more than 64.000 persons are newly diagnosed with cancer every year. In 2009, cancer was responsible for 27.023 deaths. Figure 2 shown on the page overleaf illustrates cancer related mortality in Belgium with a breakdown by the different types of tumors.

Today in Belgium, life expectancy is an estimated 82 years for men and 87 years for women. These figures represent a great challenge in terms of forecasting healthcare management needs so that treatment costs can be covered. Current estimates show that 1 in 9 women will encounter breast cancer in their lifetimes, and that 1 in 6 men will be faced with prostate cancer at some point in their lives. Nevertheless, one should bear in mind that although 80% of prostate biopsies in men over 80 years of age show the presence of prostate cancer cells, the mortality rates from prostate cancer remain somewhat low (4%). Since the introduction in 1981 of the PSA (prostate specific antigen) test, 9500 patients are diagnosed with prostate cancer each year in Belgium. On the whole, however, this type of tumor is in many cases a “dormant disease”. Hence the difficulty for health specialists is to identify those patients who need more aggressive treatment.

Concerning data on Belgian children, the Belgian National Cancer Registry indicates that each year 320 children (between 0 and 14 years) are newly diagnosed with cancer, and the most frequently encountered types of cancer are leukemia and brain tumors. However, the survival rate of these children has improved dramatically in the past few years, and the 5 year survival rate is now 84% for boys and 86% for girls.

Figure 3

Number of new cancer diagnosed in Belgium in 2011

Source: Belgian National Cancer Registry

Cancer and immortality

The lifespan of each of our cell is divided in three stages: its creation, its division, and its programmed death in a process called apoptosis. A cancerous cell is one that has found the recipe for immortality. The malignant cell continues to reproduce, invades tissues, disseminates, and creates remote metastases.

Cancer can originate as a result of several factors: tobacco, alcohol, sun, asbestos, benzene, viruses (e.g. Epstein Barr, human papillomavirus (HPV) and hepatitis as well as many other factors that stimulate and affect...