Second malignancies after treatment for laparotomy staged IA-IIIB Hodgkin's disease: long-term analysis of risk factors and outcome

Abstract

The survival of patients with Hodgkin's disease has dramatically improved over the past 30 years because of advances in treatment. However, concern for the risk of long-term complications has resulted in a number of trials to evaluate reduction of therapy. The consequences of these trials on recurrence, development of long-term complications, and survival remain unknown. One major consequence of successful treatment of Hodgkin's disease is the development of second malignant neoplasms. We sought to determine the factors most important for development of second tumors in pathologically staged and treated Hodgkin's disease patients followed for long intervals to provide background information for future clinical trials and guidelines for routine patient follow-up. Between April 1969 and December 1988, 794 patients with laparotomy staged (PS) IA-IIIB Hodgkin's disease were treated with radiation therapy (RT) alone or combined radiation therapy and chemotherapy (CT). There were 8,500 person-years of follow-up (average of 10.7 person-years per patient). Age and gender-specific incidence rates were multiplied by corresponding person-years of observation to obtain expected numbers of events. Observed to expected results were calculated by type of treatment, age at treatment, sex, and time after Hodgkin's disease. Absolute (excess) risk was expressed as number of excess cases per 10,000 person-years. Seventy-two patients have developed a second malignant neoplasm. Eight patients developed acute leukemia, 10 had non-Hodgkin's lymphoma (NHL), and 53 patients developed solid tumors at a median time of 5 years, 7.25 years, and 12.2 years, respectively, after Hodgkin's disease. One patient developed multiple myeloma 16.5 years after Hodgkin7s disease. The relative risk (RR) of developing a second malignancy was 5.6. The absolute excess risk per 10,000 person-years (AR) of developing a second malignancy was 69.6 (7.0% excess risk per person per decade of follow-up). The highest RR occurred for the development of leukemia (RR = 66.2), however because of the low expected risk, the AR was only 9.3. The RR of solid tumors after Hodgkin's disease was lower (4.7); however, the AR was greater (49) than for acute leukemia. Among the solid tumors, breast, gastrointestinal, lung, and soft tissue cancers had the highest absolute excess risks. The risk for developing breast cancer after Hodgkin's disease was greatest in women who were under the age of 25 at treatment. The most significant risk factor for the development of both leukemia and solid tumors was the combined use of radiation therapy and chemotherapy. The RR following RT alone was 4.1 (AR = 51.1); for RT + CT (initially or at relapse) the RR was 9.75 (P < 0.05, nonoverlapping confidence limits, AR = 123.9). Survival following development of a second malignancy was poor in patients with leukemia, gastrointestinal tumors, lung cancer, and sarcoma. Survival from other malignancies including NHL and breast cancer was more encouraging. Second malignant neoplasms are a major cause of late morbidity and mortality following treatment for Hodgkin's disease. The most significant risk factor for the development of second tumors is the extent of treatment for Hodgkin's disease. Recommendations are presented for both prevention and early detection of these tumors.

Myelodysplastic syndrome and acute myeloid leukemia after receipt of granulocyte colony‐stimulating factors in older patients with non‐Hodgkin lymphoma

“…Our study was focused on a population of Medicare‐aged patients with NHL; however, the risk of treatment‐related MDS/AML is greater among younger patients with cancer. An age‐dependent, radiation‐related risk of leukemia has been demonstrated, with higher rates of secondary MDS or AML observed in younger patients with Hodgkin lymphoma and breast cancer when combined with multiple chemotherapy. With more potential survival years beyond NHL diagnosis, aggressive and dose‐intensive treatment strategies in younger patients are accompanied by a greater lifetime risk of myeloid leukemia.…”

Second primary head and neck cancer after Hodgkin lymphoma: A population‐based study of 44,879 survivors of Hodgkin lymphoma

“…There have been several reports describing the incidence of second primary HNC after HL based on a relatively small number (<10) of patients with HNC after HL. [11][12][13][14][15][16] Moreover, it has been previously reported, based on SEER data from 1973 through 2003, that survivors of HL who received radiotherapy for HL were 16.9 times more likely to develop salivary gland cancers (SGCs) compared with a matched control population. 17 In the current study, we examined population characteristics among patients with HL who later developed HNC and assessed the effect of a history of HL on survival after second primary HNC by comparing these patients with patients with a first primary HNC.…”

Time interval to the development of breast carcinoma after treatment for Hodgkin disease

“…Through the use of comprehensive radiotherapy and combination chemotherapy regimens, the prognosis for patients with Hodgkin disease (HD) has improved dramatically in the last several decades. Radiotherapy and alkylating chemotherapy agents are themselves carcinogenic and, unfortunately, the dramatic gains in survival for patients with HD have been accompanied by a significant increase in the risk of secondary malignancies 1–22. The leading cause of death among 15‐year survivors of HD is second cancers 23–25.…”