Risk Of Second Cancers Greatest In Younger Patients Treated For Non-Hodgkins Lymphoma

For survivors of non-Hodgkin's lymphoma the risk of developing subsequent secondary cancers is greater the younger the patient's age at diagnosis, concludes a study published in the Journal of Clinical Oncology. The study also showed that the toll of subsequent solid tumors was largest 21 to 30 years after diagnosis.

Non-Hodgkin's lymphoma (NHL) is a cancer affecting the lymphocytes (white blood cells in the lymphatic system), which are important components of the immune system. Lymphomas are divided into two distinct types - Hodgkin's lymphoma and non Hodgkin's lymphoma, which can be distinguishable under the microscope according to the shape of the cancerous cells. In NHL lymph nodes in many different parts of the body can be involved, including the stomach, small bowel, bones, brain, testicles and skin. In Western Europe NHL affects around 11 people per 100,000 of the population and represents the seventh most common type of cancer. For reasons that are not entirely clear, the incidence of NHL has gradually increased over the last 40 to 50 years.

Initially patients with NHL were treated with radiotherapy, then in the 1970s multi drug chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) was introduced. This was followed in the 1980s by innovations in autologous bone marrow transplantation with very high-dose chemotherapy (often with cyclophosphamide or other alkylating agents) for patients with relapsing high-grade NHL. A number of different studies have suggested that patients treated for NHL have a higher risk of developing secondary tumors in a range of different sites than the general population.

Kari Hemminki and colleagues, from the German Cancer Research Center (Heidelberg, Germany), together with investigators from the Karolinska Institute and Norrlands University Hospital (Umea, Sweden), used the Swedish Cancer Registry to identify patients diagnosed with NHL. In the study 28,131 patients who were recorded as having primary NHL were followed until December 31, 2004 to see if they went on to develop a second primary cancer.

In the current paper, Hemminki and colleagues compared the incidence of second malignancies among NHL patients with the incidence of these malignancies in the general Swedish population, who had not suffered from NHL. From this investigators calculated the standardized incidence ratio (SIR) for each cancer, which gives a measure of incidence compared with the general population. In addition, separate analysis were undertaken according to age of patients at NHL diagnosis and the time elapse since NHL diagnosis that the malignancy took to develop.

The novel aspects of the study (which focused on solid tumors as opposed to lymphohematopoietic neoplasms) is that in addition to the large sample size from a single country they were able to include a wide age range at NHL diagnosis.

Results show that the overall SIR for solid tumors after NHL in the study was 1.65 - i.e. people who have had NHL are 1.65 times more likely to develop other cancers than the general population who have never had NHL.

Among the 25 most common solid tumors the incidence among patients with NHL compared with the normal population increased in 16 different tumor types. The only decreased risk was observed for endometrial cancer, which was shown to be half that of the general population. (SIR=0.52). The highest risk observed was for spinal meningioma (40.8), followed by cancers in the nervous system excluding the brain (18.1), with other common sites including the thyroid (6.49), and nose (5,96).

A separate analysis showed that the overall SIRs for solid tumors declined with increasing age at diagnosis. It was 4.52 (i.e. 4.52 times that of the normal population) for people diagnosed with NHL below the age of 20, compared to 3.03 for patients diagnosed between 20 to 39, 1.59 for those between 40 and 49, 1.55 for those between 50 and 59, 1.48 for those between 60 and 69, and finally 1.12 for those aged 70 plus. An additional finding was that the development of solid tumors was greatest 21 to 30 years after diagnosis.

The results, say Hemminki and colleagues, provide valuable insights into the carcinogenic process. "The initially high relative risks in young patients probably reflect sensitivity of the growing organism to an aggressive and potentially carcinogenic therapy," they write, adding that the castrating effects of NHL therapy may offer an explanation for reductions in endometrial cancer, a hormone sensitive tumor.

The fact that tumor toll is largest 21 to 30 years after diagnosis has important implications for the timing of medical surveillance schemes for patients with NHL. "Longer follow-up periods of patients will be needed to fully characterize the long-term effects of NHL therapy," they write, adding the individual solid tumors are likely to show variable responses.

Limitations of the study, write the authors, include lack of data about treatments, short follow-up times, small number of subjects after the subdivisions of the initially large study population, and the large increases in the incidence of NHL during the study period.

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