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Risk of Subsequent Malignant Neoplasms Is Low in Children With Hodgkin Lymphoma
A study published in Blood suggests that children and adolescents with intermediate-risk Hodgkin lymphoma have a relatively low cumulative risk of developing subsequent malignant neoplasms ( SMNs ), but radiation therapy appears to increase the risk of SMNs in these patients . The findings were published by Lisa Giulino-Roth , MD , of the Weill Cornell Medical College in New York , and colleagues from the Children ’ s Oncology Group .
In this analysis , researchers studied a group of 1,734 children , adolescents , and young adults who received a new diagnosis of intermediate-risk Hodgkin lymphoma between 2002 and 2009 who participated in the Children ’ s Oncology Group phase III study AHOD0031 . participants were treated with response-based therapy consisting of four cycles of a chemotherapy backbone comprising doxorubicin , bleomycin , vincristine , etoposide , prednisone , and cyclophosphamide ( ABVE-PC ). Treatment was administered with or without field radiation therapy .
Patients who were determined to have a rapid early response after two cycles of ABVE-PC and a complete response following four cycles were randomized to receive 21 Gy involved field radiation therapy ( IFRT ) or no further therapy . In contrast , patients with a slow early response to two cycles of ABVE-PC received a total of four cycles of ABVE-PC , with or without an additional two cycles of dexamethasone , etoposide , cisplatin , event-free survival ( EFS ) and overall survival ( OS ).
At time of diagnosis , the mean age of the overall cohort was 14.5 ± 3.4 years . The estimated 10- year EFS was 81.5 % and the 10-year OS was 96.1 %.
A total of 17 patients developed an SMN during follow-up ( 1 %), while the remaining 1,694 patients had no SMN . Across the entire cohort , the 10-year cumulative incidence of SMN was 1.3 %. SMNs included :
• acute myeloid leukemia ( AML ; n = 3 )
• solid tumors ( n = 11 )
• non-Hodgkin lymphoma ( n = 3 )
There were no differences in baseline clinical or demographic characteristics between patients with or without subsequent malignant neoplasms ( SMN ), but radiation therapy , non-white race , and B symptoms were associated with a higher SMN risk .
There were no differences between patients with versus without SMN at baseline in terms of clinical or demographic characteristics , the authors noted . “ Of note , none of the patients with therapy-related AML in our cohort received DECA , which is relevant as excess risk for leukemia has been reported following treatment with etoposide and cisplatin ,” they added .
As seen in the TABLE , the standardized incidence ratio for any SMN was 9.5 , with a corresponding absolute excess risk of 1.2 per 1,000 person-years .
Researchers reported that the cumulative incidence of SMNs was significantly higher in patients who were treated with radiation therapy ( p = 0.037 ).
Other factors associated with SMN risk in a multivariate analysis included :
This trial evaluated a response-adapted therapeutic approach designed to mitigate long-term toxicities in Hodgkin lymphoma , while ensuring the maintenance of high cure rates . All eligible cytarabine ( DECA ). All patients with a slow early response received IFRT .
The researchers performed an assessment of SMNs at a median follow up of 7.3 years , as well as
• race ( Asian vs . white : hazard ratio [ HR ] = 7.8 ; Black vs . white : HR = 0.8 ; p = 0.028 )
• B symptoms ( HR = 3.1 ; p = 0.027 )
TABLE . Standardized Incidence Ratio and Absolute Excess Risk of Subsequent Malignant Neoplasms
Cancer Diagnosis
Observed Cases
Expected Cases
Standardized Incidence Ratio
95 % CI
Absolute Excess Risk
Any subsequent malignant neoplasm |
17 |
1.79 |
9.5 |
4.5-15.2 |
1.2 |
Solid tumor within radiotherapy field |
10 |
0.1 |
105.1 |
83.2-193.4 |
0.8 |
Myelodysplastic syndromes / acute myeloid leukemia |
3 |
0.012 |
249.9 |
195.7-730.3 |
0.2 |
Non-Hodgkin lymphoma |
2 |
0.02 |
94.4 |
63.7-340.9 |
0.2 |
Osteosarcoma |
1 |
0.0668 |
14.7 |
5.5-81.9 |
0.1 |
Embryonal carcinoma |
1 |
0.027 |
37.4 |
17.9-207.8 |
0.1 |
Papillary thyroid carcinoma |
6 |
0.06 |
100.1 |
76.9-217.8 |
0.5 |
Mucoepidermoid carcinoma |
1 |
0.008 |
119.4 |
68.1-664.5 |
0.1 |
Renal cell carcinoma |
1 |
0.005 |
207.4 |
124.5-1153.7 |
0.1 |
Breast cancer |
1 |
0 |
Not available |
Not available |
0.1 |
• receipt of radiation therapy ( HR = 8.6 ; p = 0.040 )
“ The reasons for these associations , other than treatment with radiation therapy , remain unclear and these associations have not previously been noted ,” the authors concluded , adding that the relatively short follow-up period was a limitation of this study . “ Further follow-up with this cohort and in other cohorts is required to further evaluate these associations .”
Study authors report no relevant conflicts of interest .
Reference Giulino-Roth L , Pei Q , Buxton A , et al . Subsequent malignant neoplasms among children with Hodgkin lymphoma : A report from the Children ’ s Oncology Group . Blood . 2020 December 11 . [ Epub ahead of print ]
30 ASH Clinical News March 2021