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Retinoblastoma (RB) is the most common ocular neoplasm in children, whose development depends on two mutational events that occur in both alleles of the retinoblastoma susceptibility gene (RB1). Regarding the nature of these mutational events, RB can be classified as hereditary if the first event is a germline mutation and the second one is a somatic mutation in retina cells or nonhereditary if both mutational events occur in somatic cells. Although the rate of survival of RB is significantly elevated, the incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the main cause of death in these patients. Furthermore, evidence confirms that hereditary RB survivors are at a higher risk for SMNs than nonhereditary RB survivors. This risk seems to increase with the use of ionizing radiation in some therapeutic approaches commonly used in the treatment of RB.
Authors | Sample Size | Treatment (# Patients) |
Type of SMNs | Treatment Related to SMNs (# Patients) a |
SMNs Location (# SMNs) b |
---|---|---|---|---|---|
Mohney et al. (1998) [11] | 180 patients:
|
Hereditary: RT (60); ChT (15); Unknown (7) Nonhereditary: Not disclosed |
Hereditary: 16 (6 soft tissue tumors, 4 bone tumors, 3 melanomas, 3 carcinomas—1 breast, 1 pancreas, and 1 thyroid) Nonhereditary: 3 (1 benign soft tissue tumor and 2 carcinomas—cervical and breast) |
Hereditary: EBRT (6); EBRT + CT (4); RA (3); EBRT + BT + RA (1); ChT (1); Unknown (1) Nonhereditary: RA (1); Unknown (2) |
Hereditary: In-field of irradiation (4); outside field of irradiation (10) Nonhereditary: In-field of irradiation (1) |
Kleinerman et al. (2005) [12] | 1601 patients:
|
Hereditary: Surgery (94); ChT (16); RT (466); RT + ChT (383); Unknown (4) Nonhereditary: Surgery (480); ChT (40); RT (67); RT + ChT (47); Unknown (4) |
Hereditary: 260 (75 bone, 34 connective and soft tissue, 32 nasal cavities, 29 cutaneous melanomas, 17 eye and orbit, 10 brain, 10 female breast…) Nonhereditary: 17 (7 female breast, 2 brain, 2 thyroid, 1 Hodgkin’s lymphoma, 1 leukemia…) |
Hereditary: RT (241); No RT (19) Nonhereditary: Not disclosed |
Not disclosed |
Marees et al. (2008) [13] | 668 patients:
|
Hereditary: Surgery (70); ChT (16): RT (152); RT + ChT (58); Unknown (2) Nonhereditary: Surgery (322); ChT (8): RT (22); RT + ChT (8); Unknown (10) |
Hereditary: 62 (20 soft tissue, 16 bone tumors, 13 melanomas, 11 epithelial—4 bladder, 3 lung, 2 breast, and 2 non-Hodgkin lymphomas) Nonhereditary: 12 (5 solid cancers, 3 soft tissue, 2 lung, and 2 leukemia) |
Hereditary: EBRT (38); EBRT + ChT (17); Surgery (3); Laser coagulation (3); Unknown (1) Nonhereditary: Surgery (12) |
Hereditary: In-field of irradiation (22); outside field of irradiation (33) Nonhereditary: In-field of irradiation (0); outside field of irradiation (0) |
MacCarthy et al. (2013) [14] | 1927 patients:
|
Not disclosed | Hereditary: 146 (33 leiomyosarcoma, 33 osteosarcomas, 14 melanomas, 15 brain/CNS, 9 female breast, 9 meningiomas, 8 bladder…) c Nonhereditary: 23 (3 osteosarcomas, 4 brain/CNS, 3 meningioma, 2 female breast, 2 melanomas…) c |
Not disclosed | Hereditary: In-field of irradiation (45); outside field of irradiation (70) Nonhereditary: In-field of irradiation (6); outside field of irradiation (14) |
Gregersen et al. (2020) [15] | 323 patients
|
Hereditary: RT (31); RT + ChT (6); RT + ChT + enucleation (13); RT + enucleation (93); ChT (2); ChT + enucleation (7); enucleation (171) Nonhereditary: RT (25); RT + ChT (6); RT + ChT + enucleation (11); RT + enucleation (75); ChT (2); ChT + enucleation (2); enucleation (12) |
Hereditary: 25 (14 sarcomas, 6 melanomas, 3 carcinomas—2 breast and 1 ovarian cancer—and 2 CNS) Nonhereditary: 13 (5 carcinomas—2 lung, 1 breast, 1 cervical cancer, and 1 thyroid cancer—4 sarcomas, 3 melanomas, and 1 CNS) |
Hereditary: EBRT (13); No EBRT (12) Nonhereditary: EBRT (0); No EBRT (13) |
Hereditary: In-field of irradiation (6); outside field of irradiation (7) Nonhereditary: In-field of irradiation (0); outside field of irradiation (0) |
Schonfeld et al. (2021) [16] | 2052 patients:
|
Hereditary: RT (550); RT + ChT (435); ChT (39); Surgery (90); Unknown (14) Nonhereditary: RT (101); RT + ChT (86); ChT (61); Surgery (636); Unknown (40) |
Hereditary: 265 (89 soft tissue sarcomas, 80 bone tumors, 28 melanomas, 12 breast, 11 nasal cavity, 8 pineoblastoma, 6 CNS…) d Nonhereditary: 27 (8 breast, 3 melanomas, 3 gastrointestinal, 2 thyroid, 2 lung…) d |
Not disclosed | Not disclosed |
Zhao et al. (2021) [17] |
62 patients
|
RT (35); Chemotherapy (17); Surgery (16); Unknown (5) e | Hereditary: 40 (37 sarcomas, 4 breast cancers, 3 adenocarcinoma, 2 meningiomas, 2 thyroid carcinoma...) Nonhereditary: 17 (11 sarcomas, 4 carcinomas...) |
Hereditary: RT (27); No RT (10) Nonhereditary: RT (7); No RT (10) |
Not disclosed |
Sethi et al. (2013) [18] |
86 patients | Proton therapy (55) Photon therapy (31) |
Proton therapy: 1 (osteosarcoma) Photon therapy: 4 (3 sarcomas—orbital, maxillary, temporal bone—and 1 glioblastoma multiforme) |
Proton therapy: In-field of irradiation (0); outside field of irradiation (1) Photon therapy: In-field of irradiation (4); outside field of irradiation (0) |
|
Mouw et al. (2014) [19] |
60 tumors f | PRT (60) g | Hereditary: 1 (osteosarcoma of the femur) Nonhereditary: 0 |
Hereditary: In-field of irradiation (0); outside field of irradiation (1) Nonhereditary: In-field of irradiation (0); outside field of irradiation (0) |