Continuous Decline in Second Malignancy Occurrence in Patients with Hodgkin Lymphoma; Analysis of 1670 Patients Over the Past 5 Decades

The treatment of Hodgkin's lymphoma has radically changed over time. The current treatment can achieve a high cure rate with less long-term side effects. We undertook this retrospective study from a single institution to determine how the rate of second malignancy (SM) has changed with the change in therapy and over the past five decades.

1670 patients diagnosed with Hodgkin's lymphoma between 1956 and 2009, were the subjects of this study. Characteristics examined included: age, gender, stage, B symptoms, bulk of the disease, type of chemotherapy, radiation (dose and field), type of radiation, relapse occurrence, treatment for relapse, type and date of occurrence of SM, status at last follow up.

We looked at the relation between patient's characteristics, type of treatment, and time frame in which the treatment was delivered and the risk of developing SM.

Pearson's χ² was used to analyze the difference in characteristics. Hazard ratios were calculated using logistic regression analysis for potential risk factors. Multivariate analysis was performed to determine the unique contribution of all significant variables in univariate analysis.

Second malignancy was significantly associated with time frame at diagnosis, type of chemotherapy delivered, radiation type, dose, and field used.

Out of 1670 patients 225 developed SM, 157 solid and 68 hematologic. Compared to patients treated after 1995, patients treated before 1985 had a statistically significant higher risk of developing SM (HR=6.2); same for those treated between 1985 and 1995 (HR=3.9), P< 0.0001. Patients who received MOPP therapy had a statistically higher risk of SM (HR=4.6) compared to patients treated with ABVD chemotherapy. Use of Cobalt radiation had a HR= 2.3 for developing SM (P<0.0001) compared to the use of linear accelerator. Radiation dose of > 36 Gy (HR=1.5; p=NS) the use of mantle field radiation in females (HR=2.9; p=0.004), and the use of subtotal nodal radiation (HR=1.9;p=0.03) were associated with a higher risk. Patients who developed cardiac disease had also a higher risk for SM (HR=3.2;p<0.0001).

Risk for death was statistically associated with male gender (HR =0.7 for female; P<0.0001), Age > 60 (HR=8.8; P<0.0001), stage (HR advanced =3.5; P<0.0001), B symptoms (HR=1.5; p=0.001), use of Cobalt (HR=4.3; p<0.0001), subtotal nodal radiation (HR=3.9; P<0.0001) with females having a higher risk for death compared to males (HR= 8 for females versus 2.6 for males), MOPP chemotherapy (HR=3.9;p<0.0001), relapse (HR=7.0; p<0.0001), and occurrence of second malignancy (HR=3.9 for hematological, and 2.4 for solid; P<0.0001 for both). The risk of death decreased significantly comparing patients treated before 1970 (used as a reference) to those treated between 1971–1985, 1986–1995, and 1996–2009 with a HR of 0.6, 0.1, and 0.1 respectively (p< 0.0001). Multivariate analysis showed that the two most important predictors for occurrence of SM are the time frame at diagnosis and relapse (HR 4.2; P=0.0008 and 4.5; p<00001,respectively).

Our data suggest that the improvement in HL cure rate using less toxic frontline regimens, and the use of modern radiation therapy techniques of smaller fields is associated with a continuous decrease in the rate of SM

No relevant conflicts of interest to declare.