The incidence of second neoplasms following megavoltage radiation for pediatric tumors

Potish, Roger A.; Dehner, Louis P.; Haselow, Robert E.; Kim, Taewan H.; Levitt, Seymour H.; Nesbit, M. E.

doi:10.1002/1097-0142(19851001)56:7<1534::aid-cncr2820560711>3.0.co;2-o

Cited by 50 publications

(23 citation statements)

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“…One report (Potish et al, 1985) (Sawitsky et al, 1966), but even if this child is excluded our estimate gives an incidence of 6.7% second malignancies at 7 years. A comparable figure of 9.9% at 9 years was reported in adult Hodgkin's disease (Pedersen-Bjergaard & Larsen, 1982).…”

Section: Discussionmentioning

confidence: 65%

Second malignancies in children treated for non-Hodgkin's lymphoma and T-cell leukaemia with the UKCCSG regimens

Ingram¹,

Mott²,

Mann³

et al. 1987

Br J Cancer

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Summary Eight children treated between 1977 and 1983 with the UK Children's Cancer Study Group's nonHodgkin lymphoma (NHL) and T-cell protocols have developed second malignancies within 7 years of commencing treatment. Five developed acute non-lymphoblastic leukaemia and a sixth died from infection while pancytopenic with a pre-leukaemic marrow. The other malignancies were cerebral astrocytoma and an undifferentiated low grade sarcoma.These eight children were included among 261 children studied in the first UKCCSG NHL and T-cell trials giving an actuarial incidence of 7.8% second malignancy at 7 years. Six had received adjuvant radiotherapy which may have contributed to the high incidence of second malignancy.Children with non-Hodgkin's lymphoma (NHL) have been shown to respond to intensive combination chemotherapy based on schedules such as the LSA2-L2 protocol (Wollner et al., 1976). The UK Children's Cancer Study Group (UKCCSG) devised a similar protocol which was given to children presenting between July 1977 and July 1983 with NHL or T-cell leukaemia/lymphoma (Mott et al., 1984a, b). Failure free survival rates at 4 years of 65% for children without mediastinal disease and 37% for T-cell leukaemia/lymphoma were achieved.Recently three children treated with these protocols were reported to have developed acute myeloid leukaemia (Haworth et al., 1985;Rose et al., 1985;Darbyshire & Mott, 1986). We report 3 additional patients with acute leukaemia or pre-leukaemia and 2 other cases of second malignancy viz: cerebral astrocytoma and undifferentiated sarcoma. A Kaplan-Meier estimate of the risk of second malignancy is derived for these 8 patients. Patients, protocols and methodsThe protocols are shown in Figure 1. Remission was induced with two courses of cyclophosphamide, adriamycin, vincristine and prednisolone followed by cytosine and thioguanine. The remission was consolidated with intermediate dose intravenous methotrexate, with additional asparaginase, vincristine and prednisolone for the T-cell patients. Intrathecal methotrexate was given as prophylaxis for meningeal disease, together with cranial radiotherapy for T-cell disease and patients were allocated at random either to no further treatment or to low dose radiation (15Gy) to the initial sites of bulk disease. This was followed by maintenance chemotherapy including the alkylating agents cyclophosphamide and CCNU. Total treatment time from first diagnosis was 2 years.There were 261 patients registered in the UKCCSG studies, 166 treated with NHL, 95 with the T-cell protocol. The eight second malignancies reported here were among these 261 patients. Their case records and histological specimens have been reviewed. The staging system is that of Murphy and Hustu (1980). The three patients reported previously were case 4 (Haworth et al., 1985), case 5 (Darbyshire & Mott, 1986) and case 6 (Rose et al., 1985). originally diagnosed as NHL but as 56% of the marrow cells were lymphoblasts, he actually had leukaemia. This was not fully characterised; the blasts ...

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Section: Discussionmentioning

confidence: 65%

Second malignancies in children treated for non-Hodgkin's lymphoma and T-cell leukaemia with the UKCCSG regimens

Ingram¹,

Mott²,

Mann³

et al. 1987

Br J Cancer

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“…However, standardised incidence ratios by time periods after FPC diagnosis were not published. One hospital-based study of 330 children treated by radiotherapy observed a cumulative incidence of second cancer of 1.7%, 25 years after FPC (Potish et al, 1985). The standardised incidence ratio is not given, but one can infer from the cumulative incidence that it was probably smaller than 2.…”

Section: Discussionmentioning

confidence: 95%

“…Estimation of the 25 years cumulative incidence of second cancer after childhood cancer varies from 1.7% (Potish et al, 1985) to 12.1% (Tucker et al, 1984).…”

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confidence: 99%

Long-term risk of second malignant neoplasm after a cancer in childhood

Vathaire

Schweisguth²,

Rodary³

et al. 1989

Br J Cancer

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Summary The risk of subsequent second malignant neoplasm was studied in a cohort of 634 patients, treated for a childhood cancer at the Gustave Roussy Institute between 1942 and 1969, and in complete remission five years after diagnosis. The most frequent types of first primary cancers (FPC) were Wilms' tumours (28% of the children), neuroblastomas (16%), lymphomas (12%) and soft tissue sarcomas (11%). Median follow-up duration after FPC was 19 years. Thirty-two patients (obs=32) developed a total of 35 second cancers. Bone, thyroid, connective tissues and skin were the most frequent types of second cancer, with six patients for each type. The average annual incidence of second cancer was 0.36%. The average annual incidence for the periods 5-9, 10-14, 15-19, 20-24 and 25+ years after FPC was respectively 0.16%, 0.34%, 0.36%, 0.71% and 1.18%. The cumulative incidence of second cancer for the periods 5-20, 5-25 and 5-30 years after FPC was, respectively, 4.3% (95% Cl: 2.8-6.6%), 7.8% (95% Cl: 5.1-11.8%) and 13.0% (95% CI: 8.2-20.0%). The expected number of cancers in the cohort, computed from Danish cancer incidence data, was exp=2.2. When compared to this expected number, the average annual excess incidence of second cancer, defined as obs-exp divided by the number of person years of observation, was 0.33%. This rose from 0.15% for the period 5-9 years after FPC to 1.09% for the period beginning 25 years after FPC. The standardised incidence ratio of second cancer (i.e. obs/exp) was 15 (95% CI: 10-21), and was fairly constant in the period extending from 15 to 20 years after FPC diagnosis. Obs/exp was equal to 25 for the patients who had had chemotherapy and equal to 9 for those who had not. Cyclophosphamide seemed less carcinogenic than the other alkylating agents. Obs/exp was similar for the patients who had received radiotherapy and for those who had not. The risk of cancer increased with age in the reference population and increased faster in the cohort, because the standardised incidence ratio is constant over a long period.

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“…Although a genetic predisposition for cancer and previous chemotherapy may be contributing causes to the development of SNs, 5 various reports have highlighted the significant contribution of radiotherapy to the development of SNs in childhood cancer survivors. 3,[5][6][7][8][9][10][11][12][13][14][15][16][17][18] A radiation dose-effect relationship has been noted for some SNs such as bone sarcomas. 15 Children are particularly susceptible to the carcinogenic effects of radiation, possibly due to the increased rapidity of cell division in various tissues associated with the normal growth and development process.…”

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confidence: 80%

“…Earlier reports from the University of Minnesota have analyzed the incidence and nature of SNs in a cohort of children who received megavoltage radiation after 1954. 9,19 The current report updates these original studies, but with increased numbers of children in the cohort and a longer follow-up time.…”

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confidence: 99%

Second neoplasms after megavoltage radiation for pediatric tumors

Gold¹,

Neglia²,

Dusenbery³

2003

Cancer

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BACKGROUNDBecause ionizing radiation is a known carcinogen, diligent long‐term follow‐up in children exposed to therapeutic radiation is required. The authors updated an earlier study on the nature and risk of second neoplasms (SN) in patients treated with megavoltage radiotherapy as children.METHODSThe authors followed 446 children who were treated for a primary malignancy with megavoltage radiotherapy between January 16, 1954 and December 31, 1980. These children survived a minimum of 5 years. The nature and incidence of SNs were evaluated in this population. Patients with bilateral retinoblastoma or neurofibromatosis were excluded from the study due to their large genetically based predisposition for developing an SN.RESULTSThe Kaplan–Meier actuarial survival rate was 80% (95% confidence interval [CI] 74–85%) at 30 years for all patients. Thirty‐seven (8.3%) patients developed SNs, most of which occurred within the original radiation treatment field, 3.8–31.8 years (median, 15.5 years) after radiotherapy. The cumulative risk of developing an SN was 13% (95% CI 9–19%) at 30 years and the standardized incidence ratio for the development of any SN was 5.2 (95% CI 3.4–7.6%). The most common SNs were breast carcinoma (n = 8), skin carcinoma (five basal cell carcinomas, two malignant melanomas, and one dermatosarcoma), and meningiomas (n = 6). All eight breast carcinomas occurred after the treatment of childhood Hodgkin disease. Of the 37 patients with SNs, 12 died of either the SN (n = 10) or of recurrent disease (n = 2). Risk factors associated with developing a SN included initial diagnosis of Hodgkin disease (P = 0.0003), female gender (P = 0.008), and an initial diagnosis of acute lymphoblastic leukemia (P = 0.02).CONCLUSIONSPatients in the radiation‐treated cohort experienced increased mortality, were at an increased risk of developing an SN, and should undergo increased medical surveillance as adults. The cumulative probability of developing an SN has increased substantially at 30 years, largely due to an increase in follow‐up time. In addition, the cumulative probability curve does not show evidence of plateau after increased duration of follow‐up. Finally, the emergence of secondary breast carcinoma in the current study was not noted in the previous analysis. Cancer 2003;10:2588–96. © 2003 American Cancer Society.DOI 10.1002/cncr.11356

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The incidence of second neoplasms following megavoltage radiation for pediatric tumors

Cited by 50 publications

References 13 publications

Second malignancies in children treated for non-Hodgkin's lymphoma and T-cell leukaemia with the UKCCSG regimens

Second malignancies in children treated for non-Hodgkin's lymphoma and T-cell leukaemia with the UKCCSG regimens

Long-term risk of second malignant neoplasm after a cancer in childhood

Second neoplasms after megavoltage radiation for pediatric tumors

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