Second malignancies in children with head and neck primary tumors.
Authors: Kebudi Rejin , Bay Buyukkapu Sema , Gorgun Omer , Iribas Ayca , Yaman Agaoglu Fulya , Kebudi Abut , Tuncer Samuray , Altun Musa 
Published: June 2021

e22014 Background: Children with primaries in the head and neck region, especially those who recieve radiotherapy (RT) are at increased risk for second malignancies (SM). This study aims to assess the incidence and outcome of SM in children with head and neck primary tumors. Methods: During 1990-2017, 3214 children with cancer were treated in theIstanbul University, Oncology Institute. The primary tumor was in the head and neck region in 1414 (651 brain tumors,289 retinoblastoma,474 other). Survivors followed up for at least 3 years from diagnosis were evaluated for second malignancies. Results: 30 SM were identified in 28 survivors (18 male,10 female) at a median of 12 years (2-26) from diagnosis. The primary diagnosis was nasopharyngeal carcinoma (NPC) in 8, bilateral retinoblastoma (RBS) in 7, embryonal brain tumors (CNST) in 8, Hodgkin lymphoma (HD) in 3, rhabdomyosarcoma(RMS) in 2. Two RBS patients who did not recieve radiotherapy developed pilocytic astrocytoma (at 2 years) and osteosarcoma of the extremity (at 4 years) each, both are alive with no evidence of disease (NED) for 3.5 and 10 years. 26 patients recieved RT: one with CNST developed MDS (at 8 years) and died due to complications after stem cell transplantation (SCT). One with NPC developed PNET of the bladder (at 5 years) and died of disease (DOD). One with relapse HD developed Langerhans cell histiocytosis 2 years after SCTand is with NED for 10 years. The other 23 developed SM in the/proximity of the RT field. These SM were 7 sarcomas (in 4 retinoblastoma,2 NPC, 1 RMS), 6 thyroid cancer (in 2 CNST, 1 RMS, 1 HD, 1 NPC), 3 meningiomas (in 2 CNST, 1 RBS), 5 carcinomas (in 4 NPC, 1 RBS), 1 basal cell carcinoma (in a recurrent re-irradiated CNST, is with NED), 1 peripheral nerve sheath tumor (in 1 HD, DOD), glioblastoma multiforme and non Hodgkin's lymphoma (in the same CNST case, DOD at 6 months). One of the NPC case developed both sarcoma (at 18 years) and carcinoma (at 25 years, NED). The RT dose (20-70 Gy) differed according to diagnosis. All survivors of thyroid cancer are with NED except one who died in an accident; of 3 meningiomas, the one with retinoblastoma who developed malignant meningioma died. Of five carciinomas as SM, two with NPC who developed carcinomas died. Of sarcomas as SM, two with fibrosarcomas are with NED at 10 years each (1NPC, 1 RMS). All patients survived for a median of 3 (0.5-16) years after SM; 16/28 (57%) are with NED at a median of 8 (1-16) years; 12 died at a median of 1.8 (0.5-4.75) years after SM. (1 CNST due to accident, 1 NPC due to infectious complications after a reconstructive surgery, 10 DOD). All SM were detected early during regular surveillance. Conclusions: Children with head and neck primaries are at risk for SM which may occur many years later, especially in RT sites. RT should be avoided when possible such as currently in RBS. Patients need regular surveillance lifelong, for early detection of SM. SM should be treated with curative intent, to achieve long term survival.