ANDREWES'S CHRISTMAS FAIRY TALE: ATYPICAL THINKING ABOUT CANCER AETIOLOGY IN 1935.

This paper uses a short 'Christmas fairy-story for oncologists' sent by Christopher Andrewes with a 1935 letter to Peyton Rous as the centrepiece of a reflection on the state of knowledge and speculation about the viral aetiology of cancer in the 1930s. Although explicitly not intended for public circulation at the time, the fairy-story merits publication for its significance in the history of ideas about viruses, which are taken for granted today. Andrewes and Rous were prominent members of the international medical research community and yet faced strong resistance to their theory that viruses could cause such tumours as chicken sarcomas and rabbit papillomas. By looking at exchanges between these men among themselves and other proponents of their theories and with their oncologist detractors, we highlight an episode in the behind-the-scenes workings of medical science and show how informal correspondence helped keep alive a vital but then heterodox idea about the role of viruses in causing cancer.

Otolaryngology and the American presidency: a medical legacy.

The various medical histories of eminent members of state have been well documented and explored. Such accounts provide interesting insights into advances in treatment and management of disease. Moreover, historical cases serve as a timely reminder of how the central tenets of good medical practice do not change with time. Two American presidents, Ulysses S. Grant and Grover Cleveland, were afflicted with diseases of the head and neck, and one would subsequently die from his illness. Here we examine their diagnosis, treatment and their disease in the context of modern management.

Pesticides, soft-tissue sarcoma and non-Hodgkin lymphoma--historical aspects on the precautionary principle in cancer prevention.

BACKGROUND: After the 2(nd) World War a long range of chemical agents have been introduced on the market, both in Sweden and most other countries. From the 1950's several pesticides gained increasing use in agriculture and forestry. In the 1970's public concern increased in Sweden especially regarding use of phenoxy herbicides to combat deciduous wood, although statements from different authorities were reassuring of the safety. MATERIALS AND METHODS: At the end of the 1970's the author and his colleagues published the first scientific evidence of an association between exposure to phenoxyacetic acids, chlorophenols and certain malignant tumours, i.e., soft-tissue sarcoma and malignant lymphoma. The study subjects were also exposed to contaminating dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Later studies showed also an association between certain persistent organic pollutants such as polychlorinated biphenyls and non-Hodgkin lymphoma (NHL) with an interaction with titers of antibodies to Epstein-Barr virus early antigen. These results have been corroborated in other studies. DISCUSSION: Over the years industry and its allied experts have attacked our studies, but in 1997 IARC classified TCDD as a human carcinogen, Group I. The increasing incidence of NHL in Sweden levelled off about 1990. The author postulated that the regulation or ban of the use of chlorophenols, certain phenoxy herbicides and some persistent organic pollutants in Sweden back in the 1970s has contributed to the now decreasing incidence of NHL. Unfounded criticism from industry experts may prohibit the precautionary principle and early warnings of cancer risk can be ignored. Cancer risks by certain chlorinated phenols may serve as a model of how the precautionary principle should be used by taking early warnings seriously.

Coley's toxins, tumor necrosis factor and cancer research: a historical perspective.

As far back as the 1700s, it was recorded that certain infectious disease processes could exert a beneficial therapeutic effect upon malignancy. Most prominent among the numerous deliberate efforts made to take advantage of these observations was that of a pioneering New York surgeon, William B. Coley, active career 1891-1936. Using a bacterial vaccine to treat primarily inoperable sarcoma. Coley accomplished a cure rate of better than 10%. This review examines the history of these efforts and presents a discussion of their corresponding relevance to present day immunotherapy.

The Evolution of Pediatric Soft Tissue Sarcoma Classification in the Last 50 Years.

This review discusses the history of the classification of soft tissue sarcomas in children and adolescents, the current transition toward integration of morphology and molecular genetics as new entities emerge, and future perspectives.

Scrotal malignancies: the University of Iowa experience and a review of the literature.

Cancer of the scrotum is of special interest, despite its relative infrequency, because of its surprising virulence and also by virtue of its historical importance. This was the first known occupational cancer and showed the need for research involving potential environmental carcinogens. No one individual has sufficient experience to randomize patients to different methods of treatment, and the disease is becoming even less common. Therefore, recommendations are often based on compilations from the literature, many reports being fifty to one hundred fifty years old. This report reviews the clinical features of scrotal malignancies and the forty-five-year experience with this disease at the University of Iowa.

When viruses were not in style: parallels in the histories of chicken sarcoma viruses and bacteriophages.

The discovery that cancer may be caused by viruses occurred in the early twentieth century, a time when the very concept of viruses as we understand it today was in a considerable state of flux. Although certain features were agreed upon, viruses, more commonly referred to as 'filterable viruses' were not considered much different from other microbes such as bacteria except for their extremely small size, which rendered them ultramicroscopic and filterable. For a long time, in fact, viruses were defined rather by what they were not and what they could not do, rather than any known properties that set them apart from other microbes. Consequently when Peyton Rous suggested in 1912 that the causative agent of a transmissible sarcoma tumor of chickens was a virus, the medical research community was reluctant to accept his assessment on the grounds that cancer was not infectious and was caused by a physiological change within the cells. This difference in the bacteriological and physiological styles of thinking appears to have been prevalent in the wider research community, for when in 1917 Felix d'Herelle suggested that a transmissible lysis in bacteria, which he called bacteriophagy, was caused by a virus, his ideas were also opposed on similar grounds. It was not until the 1950s when when André Lwoff explained the phenomenon of lysogeny through his prophage hypothesis that the viral identities of the sarcoma-inducing agent and the bacteriophages were accepted. This paper examines the trajectories of the curiously parallel histories of the cancer viruses and highlights the similarities and differences between the ways in which prevailing ideas about the nature of viruses, heredity and infection drove researchers from disparate disciplines and geographic locations to develop their ideas and achieve some consensus about the nature of cancer viruses and bacteriophages.

Radiotherapy for soft tissue sarcoma: 50 years of change and improvement.

Radiotherapy for soft tissue sarcoma (STS) has advanced significantly over the past 50 years. This review focuses briefly on the period from 1964 to 1999 and more substantially on the changes of the past 15 years, such as IMRT and image-guided radiotherapy (IG-RT), especially when brought together (IG-IMRT) in the same planning and delivery process to treat localized STS. In particular, the introduction of IG-RT, target volume definitions for IG-RT, and review of recent clinical trials using IG-RT to treat localized STS in extremity will be reviewed. Finally, potential investigational agents combined with IG-RT to improve outcomes in patients with localized STS are discussed.

Surgical advances in bone and soft tissue sarcoma: 50 years of progress.

As the American Society of Clinical Oncology celebrates its 50th anniversary, physicians can appreciate the significant advances made in the treatment of patients with sarcoma. Historically, these rare tumors have garnered great interest in the medical profession, due to their ability to reach extraordinary size, resulting in substantial deformities and disabilities. Fortunately, advances in surgical management, which have occurred concurrently with advances in imaging, diagnostic techniques, and both local and systemic adjuvant treatments, offer patients diagnosed with sarcoma significant hope for successful treatment and the expectation of a meaningful quality of life.

Fifty years of advances in sarcoma treatment: moving the needle from conventional chemotherapy to targeted therapy.

Much of the progress in systemic therapy for sarcomas was accomplished in the first half of the last 5 decades. Various chemotherapeutic agents were tested in the 70s through the 80s and became part of the standard of care for this patient population. During the decade of the 90s, dose intensification became feasible as a result of improved supportive care and the availability of growth factors, thus maximizing the therapeutic potential of this class of agents. However, response rates and survival plateaued and it became obvious that newer and mechanistically different agents were needed to improve the therapeutic index and gain further enhancement of outcomes. Since early 2000, primarily inspired by the experience with imatinib in gastrointestinal stromal tumors (GISTs), several targeted therapies have been tested in sarcomas with modest success. The major limitations encountered include the lack of drivers and actionable targets for bone and soft tissue sarcomas with complex genomic profiles. Continued investigations and sequencing of larger numbers of these rare and heterogeneous malignancies could shed some light on a path toward improved outcomes.