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Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003.

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Holland-Frei Cancer Medicine. 6th edition.

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Chapter 159Secondary Cancers: Incidence, Risk Factors, and Management

, MD, , MD, PhD, and , MD.

Second primary cancers have become an increasingly important concern in oncology during the last two decades, as they now comprise the sixth most common group of malignancies after skin, prostate, breast, lung, and colorectal cancers.1,2 This chapter discusses the prevalence and the etiologic factors responsible for second malignant neoplasms (SMNs). Methods of long-term surveillance for individuals at high risk of developing multiple malignant neoplasms are also suggested.

What was formerly a problem primarily in pediatric cancer survivors and for the survivors of the more curable adult cancers has become a more universal problem in the present-day practice of oncology. Survivors of all cancers are living for longer periods, partly because of the more frequent use of effective therapy.3 The formerly unacceptable toxicities of therapy are more readily controlled with better supportive care,4 and more patients are receiving treatment and benefiting from it. Other reasons for an increase in multiple cancers include fewer competing causes of mortality and consequently more naturally occurring cancers in an increasingly aging population.

When reviewing data on SMNs, consideration must be given to the definition. One can readily appreciate a “second cancer” as such when the second neoplasm differs histologically, or molecularly, from the primary neoplasm. But when considering incidence, how should one regard a second, histologically identical, cancer in a paired organ? Reports and analyses of data have emphasized the importance of ruling out metastatic disease when a new tumor arises, but traditionally many registries consider tumors of the same histologic type in the second of paired organs to be “second cancers.” Reports of multiple primaries should clearly state whether second cancers include or exclude non-metastatic neoplasms in paired organs.

The frequency of SMNs may be expressed as an actuarial risk within a given cohort, as a relative risk when compared with a standard population, or as an attributable risk, with the latter reflecting the additional cases associated with a specific exposure or other etiology. Each of these methods has inherent limitations when attempting to ascribe causation, especially when several factors are implicated.

In discussing causation, we first deal with the role of shared environmental risk factors. Lifestyle factors, such as smoking, alcohol, exercise, sun exposure, and diet, clearly play individual roles in a long list of cancers, such as those of the head and neck, lung, bladder, skin and gastrointestinal tract, which are often seen as secondary cancers following treatment for a primary neoplasm. Environmental risk factors continue to raise the probability for a new cancer after the diagnosis and treatment of an initial malignancy. Although cancer survivors often reduce their exposures, the effects of earlier exposure can continue to influence their risks for years.

Individuals with a genetic predisposition to multiple neoplasms are another group at risk. More than 40 genes have been cloned whose mutations are known to increase cancer susceptibility.5 The first of these, retinoblastoma, was described many years before the mutated gene was cloned, but others, including the phakomatoses, multiple endocrine neoplasias, and the deoxyribonucleic acid (DNA) repair disorders, such as hereditary nonpolyposis colorectal cancer (HNPCC), are also associated with multiple neoplasms. Studies of these mutations and their resultant disruption of cellular signaling pathways have provided insight into tumorigenesis, both in its hereditary and sporadic forms.

Polymorphisms for metabolizing enzymes are another potentially critical category of etiologic factors that cannot yet be evaluated. For example, cytochrome P450 and glutathione S-transferase variants may be important determinants of whether or not exposure to a specific environmental agent, radiation, or to chemotherapy is associated with an increased likelihood of developing a second malignant neoplasm.

SMNs are known to result from the radiation therapy and chemotherapy used to treat a primary cancer. Studies of pediatric cancer survivors have provided much information concerning the relationship of therapy to SMNs because of the young age at diagnosis and the high cure rates following successful therapy.6,7 As therapy becomes more intensive for adults as well as children, and as cure rates increase, we may expect a resultant increase in toxicity, including SMN. It should be emphasized, however, that most instances of multiple cancers in cancer survivors are random events, and, therefore, are a sign of improved survival following the first cancer diagnosis. Fear of a second primary should not outweigh considerations about or contemplation of curative therapy for the first cancer.

Registries that record information about patients with SMNs, including therapy received and family history, are valuable resources for the analysis of risk factors and for providing genetic material to laboratory scientists. As knowledge concerning risk factors for SMN increases, it will be possible to provide more focused surveillance in the follow-up of long-term survivors. Such knowledge is also useful for planning clinical trials with the objective of reducing long-term morbidity while concomitantly maintaining similar cure rates.

Contents

  • Incidence of Secondary Cancer
  • Clinical Characteristics
  • Shared Environmental Risk Factors
  • Genetic Risk Factors
  • Therapy-Related Secondary Cancers
  • Conclusion
  • References

By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 2003, BC Decker Inc.
Bookshelf ID: NBK12712

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