Second Malignant Neoplasms
Second malignant neoplasms (SMN) are nonmetastatic malignancies occurring in patients previously diagnosed with another malignant neoplasm. This clinical entity is becoming increasingly more frequent with the aging of the overall population and better diagnosis and treatment of cancers. Although a reasonable percentage of cases may be explained by genetic, iatrogenic, and/or shared environmental exposure, it is estimated that the majority of cases are sporadic. Recognizing the possibility of SMNs is essential for appropriate and timely diagnosis and treatment, but even more important for the development of preventive strategies.
Key words: oncology, second malignant neoplasms, ophthalmology, eye tumours.
A second malignant neoplasm (SMN) may be defined as a nonmetastatic malignancy that was diagnosed after another malignant neoplasm. This definition includes new primary cancers with one or more of the following features: located in a different organ, located in a different site of the same organ with a different histological type, or affecting the second of paired organs (e.g., lungs, breasts, kidneys, ovaries, testicles, or eyes).
SMNs have become increasingly important because they now represent one of the most common malignancies. In fact, SMNs rank sixth among the most frequent malignant neoplasias behind skin, prostate, breast, lung, and colorectal cancer. Data from the U.S. National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program in 1995 revealed that SMNs constitute 13.1% of cancers in men and 13.7% of cancers in women. Moreover, these frequencies had doubled over the previous 20 years.1,2 The increased incidence of SMNs in the past few decades can be attributed to some basic factors (Table 1).
The risk factors for SMNs fall into three major categories: shared environmental exposures, genetic predisposition, and iatrogenic.2
Environmental exposures may be chemical, physical, or biological. Sunlight, smoking, alcohol, and dietary habits, to name a few, are all important risk factors for the development of a number of cancers, such as those of the skin, lungs, head and neck, and gastrointestinal tract. Primary cancer survivors may still be exposed to and influenced by the same risk factors. Alternatively, they may even be subject to new environmental hazards. This increases the risk for SMN. Moreover, even if the patient is no longer exposed to a certain factor, its carcinogenic consequences may still be in effect and are manifested by a higher than normal risk of multiple cancers. For instance, cessation of smoking decreases the risk of lung cancer; however, the lifetime risk for lung cancer is still higher than that observed in nonsmokers.5-7 Additionally, smoking is also a shared risk factor for head and neck, esophageal, bladder, and renal cancer (among others).8
Genetic abnormalities, such as those related to oncogenes, tumour-suppressor genes, and DNA repair mechanisms, may cause multiple cancer syndromes. Over 40 genes implicated in the development of these syndromes have been described. Patients with genetic multiple cancer syndromes must be regularly screened for new cancers. Conversely, patients newly diagnosed with certain cancer types should be assessed for the presence of genetic abnormalities. The presence of a defined inheritance pattern aids the screening of family members and genetic counselling.
Radiation therapy and chemotherapy employed in the treatment of primary cancers may lead to a number of iatrogenic complications, including SMNs. The first observations were made in the pediatric cancer survivor population.9 As more potent treatment regimens are introduced, the number of cancer survivors in both the adult and pediatric