bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical Methods for the Analysis of Prognostic Factor Studies
Authors: McShane Lisa M. , Simon Richard 
Published: November 2003

AbstractPrognostic factor studies in cancer relate covariates describing clinical features and tumor characteristics to clinical endpoints such as therapy response, disease recurrence or progression, or survival. Examples of covariates in cancer prognostic factor studies include tumor size, nodal status, presence of metastases, and tumor‐specific measurements such as expression levels of certain proteins, presence of chromosomal aberrations, or gene mutations. Typically, the relationship between the covariates and the clinical endpoints is examined by development and testing of a prognostic model. The modeling approaches discussed in this chapter include logistic regression for binary endpoints, Cox proportional hazards regression for survival outcomes, and neural networks and recursive partitioning for both binary and survival outcomes. In the final section, techniques for model validation are discussed.
Evaluating Prognostic Factor Studies
Authors: Simon Richard 
Published: November 2003

Abstract
Most types of human cancer are heterogeneous with regard to clinical features, natural course, histologic, and molecular characteristics. Better diagnostic classification systems would improve the ability to select an appropriate treatment and facilitate the development of more effective regimens. For example, accurate classification of small breast tumors with regard to metastatic potential would permit many patients to avoid systemic therapy.
The medical literature is filled with reports of prognostic factor discoveries. There are numerous inconsistencies among reports, and for many types of cancer the literature can at best be called confusing. In contrast to clinical trials, there are no standards for prognostic factor studies, and hence it is easy to publish methodologically poor studies in reputable journals. Nearly all prognostic factor studies are “exploratory studies” rather than “confirmatory studies.” Because of problems of multiple significance testing, most conclusions of exploratory analyses will not be correct. The phenomenon of “publication bias” assures that the most positive and erroneous of these studies will be published in reputable journals and receive attention.
Technological developments are likely to make the confusion in the literature of prognostic factor studies much worse. Genomics is providing huge numbers of DNA polymorphisms that can be used as prognostic factors in future studies. DNA microarrays currently permit the expression profiling of tens of thousands of genes for each tumor sample, and these expression levels are potential prognostic factors. It is therefore important for clinical investigators and clinicians to have a better understanding of the flaws of many prognostic factor studies and to establish standards for the type of evidence about a prognostic factor that we should have before accepting the factor in clinical practice. These are the objectives of this chapter.
Psychosocial Factors in Prognosis
Authors: Edmonds Claire V.I. , Cunningham Alastair J. 
Published: November 2003

AbstractPhysicians often encounter patients' belief that psychological factors can predict survival from cancer. However, the research literature is filled with methodological shortcomings and results are often contradictory and problematic. The present brief review discusses psychosocial factors that have shown a relatively consistent relationship to survival in cancer patients.
The Role of Prognostic Factors in Cancer Research
Authors: Groome Patti A. , Mackillop William J. 
Published: November 2003

AbstractKnowledge about how the characteristics of the individual patients and their diseases will shape their future is useful when they are making decisions about their lives and when they and their doctors are making treatment decisions. When a patient's prognosis changes, new evaluation occurs that can affect further decisions about management. In all instances, knowledge about prognosis improves the quality of decisions by reducing uncertainty. In this chapter, we discuss the role of known prognostic factors in clinical research where the research products facilitate either direct or indirect improvement in the quality of clinical decision making.Figure 9.1 depicts the uses of the output of various types of clinical research and the role that prognostic factors play in that research. In research that focuses on outcome prediction, formal consideration of the combined role of known prognostic factors through the development of predictive tools can improve the clinician's ability to prognosticate. In research on treatment effectiveness, consideration of known prognostic factors allows the researcher to isolate the effect more efficiently through case selection or through the control of prognostic differences between the treatment and control groups. When subgroups defined by important prognostic factors are analyzed separately, the researcher is able to determine whether treatment is equally effective across the groups, enhancing the clinician's ability to apply research findings to different patients. In research about cancer progression and treatment resistance, identification of clinical prognostic factors can provide a starting point for better understanding of these mechanisms and possibly even disease causation, which may lead to the development of new interventions. Last, in health services research, consideration of the variations in the distributions of prognostic factors among populations of patients permits the study of health system effects.
Oral Cavity, Pharynx, and Larynx Cancer
Authors: Lefebvre Jean‐Louis , Lartigau Eric , Kara Ahmed , Sarini Jérôme 
Published: November 2003

Abstract
Cancers of the oral cavity, pharynx, and larynx occur with a yearly incidence of around 500,000 new cases. They are frequent in developed countries, about equally in North America and the European Community where they have a particularly high incidence in France. Most of these cancers are squamous‐cell carcinomas (SCCs) occurring in rather debilitated patients after a long history of tobacco consumption and alcohol abuse. The vast majority of patients are males aged around 50 years, but there is a tendency to an increasing incidence in females and young adults. In addition, the sociocultural profile of patients suffering from head and neck SCC is often poor. In general, SCCs of the head and neck often proliferate rapidly, are locally aggressive, and carry a high tendency to metastasize to cervical lymph nodes. In presentations with very large lymph nodes, or when lymph nodes are very numerous, the possibility of distant metastasis increases significantly. This natural history explains why that these SCCs are most often diagnosed at an advanced stage, requiring combined therapies. The outcome for this patient population is poor for several reasons: the risk of failure for the index tumor; the risk of developing subsequent SCCs along the upper aerodigestive tract, esophagus, and lung; and the frequency of intercurrent diseases. The risks from comorbity and second cancers arise almost exclusively from the common etiologic association with alcohol and tobacco abuse. SCCs of the oral cavity, pharynx, and larynx are a major public health problem. Apart from large campaigns against tobacco use and alcohol abuse and information that may encourage earlier diagnosis, efforts should be made to assess prognostic factors capable of predicting both outcome and the response to various treatments. In turn, this should help select appropriate therapeutic protocols.
Paranasal Sinus Cancer
Authors: Waldron John N. , Witterick Ian J. 
Published: November 2003

AbstractMalignant disease arising in the maxillary, ethmoid, frontal, or sphenoid sinuses, collectively known as the paranasal sinuses, is rare. Paranasal sinus cancer represents less than 5% of all head and neck malignancy, which in turn comprises less than 10% of malignancy overall. The majority of paranasal sinus cancers arise within the maxillary sinus (70–80%) followed by the ethmoid sinus (10–20%). Because of this, much of the literature (including the present chapter) focuses on data derived from description of tumors arising at these two sites. Cancers arising in the sphenoid or frontal sinuses are extremely rare. The outcome of patients presenting with paranasal sinus cancer is generally poor, with most centers reporting 5‐year survival rates in the range of 30–40%.As with any rare disease, the task of reliably identifying and validating independent prognostic factors for paranasal sinus cancer is complicated by the lack of prospectively collected data and the variability of data reported in the retrospective literature that spans many decades, with most series containing relatively small numbers of patients. Reports frequently describe patients with a wide range of tumor extent and histology treated with variable treatment approaches. Outcomes are often analyzed and reported with respect to different endpoints. Prognostication and empiric management recommendations are regularly based on conclusions drawn from the comparison of inhomogeneous treatment groups. In this chapter we attempt to identify prognostic factors that are supported by currently available data and, of equal importance, those that do not enjoy this support.
Nasopharyngeal Carcinoma
Authors: O'Sullivan Brian , Chong Vincent 
Published: November 2003

Abstract
Nasopharyngeal carcinoma (NPC) is unusual in several ways. Its epidemiology, associated with ethnicity, genetic predisposition, viral, and environmental dietary exposure, is unique in itself. In addition, the predilection for certain geographic areas, with relative sparing of adjacent regions is noteworthy. Unjustly perhaps, NPC poses a formidable public health hazard to countries that are relatively compromised in their ability to provide the technical diagnostic and therapeutic approaches considered to be necessary for optimal management today. However, what sets it apart from most diseases is the anatomic challenge it presents to the oncology team because of the proximity of the nasopharynx to critical anatomic structures and the high predilection for distant metastasis once the primary and regional lymph‐node areas are extensively involved, which is all too frequent.

In this chapter we discuss prognostic factors of importance in the management of NPC using the classification proposed earlier in this book. Factors will be considered by whether they relate to the
disease
itself, the patient (or
host
), or the
environment
which influences the opportunity for optimal treatment and diagnosis. The classification may not always apply since, in the case of NPC, there may be overlap among factors and arbitrary placement of factors may be necessary. We will also attempt to categorize the available evidence into factors which are essential to our ability to treat the disease (
essential
factors), those which add valuable information about the disease but do not affect treatment decisions (
additional
factors), and finally those that are being described and may provide important understanding of disease behavior and therapeutic approaches in future years. In the interest of relevance to the treatment of the disease, and for brevity, the discussion of the final group of factors (those termed
new and promising
), will be restricted to experience of patient outcome. Therefore, preclinical studies will not receive attention.

Special attention to the classification of stage of disease will be given. This is because for NPC anatomic features are so important that a relevant and reproducible system of classification merits attention above other prognostic factors. In fact, few diseases received the same level of attention in the preparation of the 5th edition (TNM) stage classification of the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC). A major revision of the NPC stage was accomplished by a substantial collaborative consultation among radiation oncologists in Southeast Asia, with support from diagnostic radiologists, pathologists, and surgeons there and elsewhere.
Cancer of the Esophagus
Authors: Stein Hubert J. , Feith Marcus 
Published: November 2003

Abstract
In contrast to other tumors of the gastrointestinal tract, independent prognostic factors have only recently been identified in patients with esophageal carcinoma. This is because most studies assessing the prognosis of patients with esophageal cancer were retrospective univariate analyses of small patient populations that were usually not treated according to standardized protocols. Due to interrelations between various patient‐ and tumor‐related factors and their alterations by therapeutic strategies, the independent prognostic effect of individual parameters cannot be deducted from these analyses. This can only be achieved by multiple stepwise regression analysis applied to a sufficiently large patient population that has undergone standardized treatment and has been followed for a sufficiently long period of time. Studies that meet these criteria have become available only during the past decade. The chapter critically reviews the currently available literature on prognostic factors in patients with esophageal cancer, which are classified into the three categories: (1) tumor‐ or disease‐related prognostic factors; (2) patient‐related factors; and (3) environment‐ or treatment‐related factors.
Malignant Thymoma
Authors: Payne David G. 
Published: November 2003

Abstract
The thymus gland, located in the anterior mediastinum, plays a crucial role in the development of immunological competence during fetal development and infancy. It is composed of both thymic epithelial cells and lymphoid cells, many originating in the bone marrow. During the development period, the complex system of T lymphocytes evolves, underpinning functions of foreign antigen processing and self‐recognition of the organism's histocompatibility complex. The gland undergoes significant involution in childhood, resulting in a twin‐lobed organ composed of fibrous, lymphatic, and epithelial elements. Its function in the adult is unknown; however, evidence for its immunologic role is seen in the involution associated with various disorders, including autoimmune diseases and AIDS, and conversely in the immunodeficiency associated with primary thymic aplasia. Tumors of the thymus are unusual, but account for about 15% of mediastinal tumors (or over 50% of masses in the anterior mediastinum). These neoplasms contain varying proportions of lymphocytes and of thymic epithelial cells, with a generally benign appearance. However, all thymomas are considered to be malignant tumors possessing differing degrees of aggressivity, or invasiveness. When frank cytologic features of malignancy are seen in epithelial cells, the tumor is regarded as a thymic carcinoma.
Clinical features typically relate to the size of the mass and proximity to other organs. The introduction of the Masaoka classification, based on the extent of local invasion by malignant cells, was an important advance in the addressing the need for comparative studies. However, the association of thymoma with various autoimmune disorders is distinctive and possibly prognostic. These conditions include myasthenia gravis, hypogammaglobulinemia, and red‐cell aplasia. Interestingly these syndromes are not associated with thymectomy in another context. A variety of other paraneoplastic syndromes are seen; about 40% of thymoma patients have one, and many suffer from multiple such disorders. For the purpose of this discussion these will be considered to be tumor‐related factors. Note that in accordance with the guidelines for this text, only factors that are required for clinical decision making are considered “essential.”
Skin Cancer
Authors: Poulsen Michael 
Published: November 2003

Abstract
The great majority of skin cancers will be cured and this has resulted in a certain degree of complacency in its management. Despite the overall favorable outlook there remains a subset of patients who remain at higher risk of relapse and indeed may even succumb to the disease. There are many prognostic factors known, but the relationships between these variables are complex and it is difficult to differentiate the independent variables from the dependent ones.
In contrast to the low recurrence rate, the risk of subsequent skin cancer elsewhere is about 50% at 5 years. The factors, which are prognostic for recurrence, are not the same as the factors, that predict for further skin cancer. Fair skin, male gender, high accumulation of solar exposure, and multiple previous basal cell carcinoma (BCC) or squamous cell carcinomas (SCCs) predict for further skin cancers.
The major types of nonmelanomatous skin cancer (NMSC) to be considered in this chapter are BCC, SCC and Merkel cell carcinoma (MCC).
Squamous‐cell Carcinoma of the Penis
Authors: Horenblas Simon 
Published: November 2003

Abstract
Squamous‐cell carcinoma (SCC) of the penis is a rare malignancy, accounting for less than 1% of urological cancers in males in Western countries. From all cancers affecting the penis more than 95% consists of SCC. Rare disorders like melanoma and soft tissue disease will not be considered in this summary. Most information regarding clinical course and prognostic factors has been based on relatively few series and case histories; there are no known prospective clinical trials in the field of penile cancer. Therefore bias, on the basis of referral pattern and institutional treatment preferences, cannot be ruled out. Moreover, there are only a few publications analyzing clinical data with multivariate prognostic factor analysis. For classification purposes, at least six classification systems of SCC of the penis have been proposed. Because the TNM system of the International Union Against Cancer (UICC) is considered the most universal used classification, the others will not be considered here.
Bladder Cancer
Authors: Bassi PierFrancesco , Pagano Francesco 
Published: November 2003

AbstractTransitional cell carcinoma of the bladder is the second most common malignancy of the genitourinary tract, and the second most common cause of death among all genitourinary tumors, the 11th most common cancer on a worldwide basis, accounting for 3–4% of all malignancies. Annually, about 220,000 new cases are being diagnosed; three‐fourths of these patients are men and a disproportional (two‐thirds) number of cases occur in developed countries.It's important to underline that a distinction between superficial bladder cancer (stages Ta, T1, Tis) and invasive bladder cancer (stages T2–T4) must be taken into account due to the different prognosis and treatment approaches. As a matter of fact, bladder cancer is a heterogeneous disease with considerable variations of its natural history with 5‐year survival rates ranging from 97% to 98% of a single, well‐differentiated, and small papillary tumor to less than 10% of an invasive bladder cancer extending throughout the bladder wall with distant metastases. Among superficial bladder cancer, tumor recurrence after initial therapy varies from 30% in patients with a solitary papillary tumor to more than 90% in patients with multiple tumors. Intense research efforts are being made to identify and characterize the different types of bladder cancer and their variable biological potential. The desire to predict which superficial bladder cancer will recur or progress to invasive cancer, and which invasive bladder cancer will metastatize has spurred the development of a variety of potential prognostic factors.In this chapter we provide a contemporary review of such prognostic factors with a particular emphasis to the reliable or potential use in the clinical practice.
Non‐
H
odgkin's Malignant Lymphoma
Authors: Crump Michael , Gospodarowicz Mary 
Published: November 2003

Abstract
The non‐Hodgkin's lymphomas (NHLs) are a diverse group of diseases with large variation in tumor biology and course of disease. The 1980s and 1990s brought a great increase in our knowledge of the biology of the immune system. Insights into the immunology and molecular genetics of NHL have led to the recognition of a number of new pathological entities, with unique natural histories. In addition, the clinical approach to patients with NHL has relied increasingly on aggregate assessment of prognostic factors, rather than single attributes such as disease stage, presence of extranodal involvement, presence of constitutional symptoms, or specific biochemical abnormalities. Furthermore, it is increasingly recognized that these biological attributes are surrogate measures of a tumor's growth and invasion potential, the host's response to the tumor, and the host's ability to tolerate treatment. A better understanding of the significance of molecular and immunological attributes of lymphoma will hopefully replace these clinical surrogates in refining NHL's prognosis and therapy more precisely in the future.
Pediatric Cancers
Authors: Marcus Karen J. , Hodgson David 
Published: November 2003

Abstract
Pediatric cancers include a broad spectrum of diseases. Cancer is diagnosed in only 8400 children in the United States less than 15 years of age annually, although death from cancer is the second major cause of mortality in developed countries. Childhood cancers differ from adult cancers in their origins and histologic subtypes, their etiologies, their response to treatment, and the outcomes. In the adult population, epithelial cancers are most common and many are related to environmental carcinogens. In contrast, pediatric malignancies more commonly arise in hematopoietic tissue or in the central nervous system (CNS).

The most common pediatric malignancies are acute leukemia, non‐Hodgkin's lymphoma, Hodgkin's disease, and primary CNS tumors. Neuroblastoma, Wilms' tumor, rhabdomyosarcoma, and retinoblastomas are the most common solid tumors occurring in children. The etiology of most childhood malignancies is unknown, although some solid tumors do occur in association with recognized genetic defects. Bilateral retinoblastoma, for instance, occurs in children with mutations in the retinoblastoma tumor suppressor gene
RB1
. Wilms' tumor occurs in association with mutations in the
WT1
gene in the Denys‐Drash Syndrome. Rhabdomyosarcomas are seen in children with the LiFraumeni syndrome with
p53
gene mutations.

Major advances in cancer genetics and the molecular biology of cancer have been gained through research in pediatric malignancies. Despite its rarity in comparison to adult malignancies, many of the most important discoveries about cancer biology and cancer genetics have come from research in pediatric cancers. In addition, the role of prognostic factors in determining treatment for an individual patient is best exemplified by neuroblastoma which is discussed in this chapter. At the present time, only a limited number of cancers in children have prognostic factors that have been prospectively evaluated and confirmed. In this chapter, we review those pediatric cancers that have clearly defined prognostic factors. The understanding of cancer genetics gained from the study of pediatric cancers, the identification of prognostic factors, their confirmation in clinical trials, and their widespread acceptance can be viewed as a paradigm for prognostic factors in cancer patient management.