The risk of second malignant tumors and its consequences for the overall survival of Hodgkin's disease patients and for the choice of their treatment at presentation: analysis of a series of 1524 cases consecutively treated at the Florence University Hospital.
OBJECTIVE
To quantify the incidence of second malignant tumors (SMT) as a whole and that of second "solid" tumors (SST) and leukemia (L) in a large series of 1524 Hodgkin's disease (HD) patients (pts) treated at the Florence University Hospital (UFH); to define the clinical and therapeutic features possibly related with SMT occurrence; to evaluate the consequences of SMT for the overall survival of the series studied and for the choice of the treatment of HD at presentation.


METHODS
From 1960 to 1991, 1524 pts with HD, Clinical Stage (CS) I--IV have been treated at the UFH. Overall treatment consisted of radiation alone (RT, 36%), chemotherapy alone (CHT, 21%), or both (RT + CHT, 43%). The cumulative probability (CP) of SMT, SST, and L was calculated for the whole series and for the different clinical and therapeutic subgroups, and the results compared with uni- and multivariate analysis ("internal" comparison, IC). Standardized incidence ratios (SIR) for different SMT types (estimated on the basis of gender, age, period specific incidence rates of the general population) have been also calculated ("external" comparison, EC). The impact of the SMT-related mortality on the survival of the entire series has been estimated.


RESULTS
A 14.9% 20-year CP of SMT was registered, along with a SIR of 2.04 (95% confidence interval [CI]: 1.2--2.5). Both IC and EC showed a statistically significant relationship between L incidence and treatment with CHT, alone or in combination with RT. A significant excess of breast cancers has been observed in RT-treated patients with longer follow-up (SIR, 2.9); an excess of other common SST (lung, non-Hodgkin's lymphomas) is evident in pts treated with either RT, RT + CHT, or CHT. The actuarial long-term survival of the series would have been better of about 3%, in absence of the SMT mortality possibly due to HD treatment, which is almost equally divided between patients treated with RT alone, CHT alone, and RT + CHT.


CONCLUSIONS
SMT represent an important late event in HD long-term survivors. The relationship between L and treatment with CHT seems to be the most clearly defined. The effect of SMT on the survival of the entire series, although not negligible, does not seem to justify by itself substantial alterations in the current standards for the treatment of HD at presentation.
Cellai
E
E
Department of Radiation Oncology, Florence University Hospital, Florence, Italy. e.cellai@dfc.unifi.it
Magrini
S M
SM
Masala
G
G
Alterini
R
R
Costantini
A S
AS
Rigacci
L
L
Olmastroni
L
L
Papi
M G
MG
Spediacci
M A
MA
Innocenti
F
F
Bellesi
G
G
Ferrini
P R
PR
Biti
G
G
D000328:Adult; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D016001:Confidence Intervals; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D015994:Incidence; D007938:Leukemia / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008466:Mechlorethamine / Q000008:administration & dosage; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D012307:Risk Factors; D012737:Sex Factors; D014750:Vincristine / Q000008:administration & dosage
D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D011241:Prednisone