Petra Temming1,2,3, Marina Arendt4, Anja Viehmann4,5, Lewin Eisele4, Claudia H D Le Guin2,6, Michael M Schündeln1, Eva Biewald6, Kathy Astrahantseff7, Regina Wieland1, Norbert Bornfeld2,6, Wolfgang Sauerwein8, Angelika Eggert7, Karl-Heinz Jöckel3,4, Dietmar R Lohmann2,3,9. 1. Department of Pediatric Hematology and Oncology, University Hospital Essen, Essen, Germany. 2. Eye Oncogenetics Research Group, University Hospital Essen, Essen, Germany. 3. German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany. 4. Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany. 5. Institute of General Medicine, University Hospital Essen, Essen, Germany. 6. Department of Ophthalmology, University Hospital Essen, Essen, Germany. 7. Department of Pediatric Oncology, Hematology and BMT, Charité-Universitätsmedizin Berlin, Berlin, Germany. 8. Department of Radiotherapy, University Hospital Essen, Essen, Germany. 9. Institute of Human Genetics, University Hospital Essen, Essen, Germany.
Abstract
BACKGROUND: Survivors of heritable retinoblastoma carry a high risk to develop second cancers. Eye-preserving radiotherapy raises this risk, while the impact of chemotherapy remains less defined. PROCEDURE: This population-based study characterizes the impact of all treatment modalities on second cancers incidence and type after retinoblastoma treatment in Germany. Data on second cancer incidence in 648 patients with heritable retinoblastoma treated between 1940 and 2008 at the German national reference center for retinoblastoma were analyzed to identify associations with treatment. RESULTS: The cumulative incidence ratio (per 1,000 person years) of second cancers was 8.6 (95% confidence interval 7.0-10.4). Second cancer incidence was influenced by type of retinoblastoma treatment but not by the year of diagnosis or by sex. Radiotherapy and systemic chemotherapy increased the incidence of second cancers (by 3.0- and 1.8-fold, respectively). While radiotherapy was specifically associated with second cancers arising within the periorbital region in the previously irradiated field, chemotherapy was the strongest risk factor for second cancers in other localizations. Soft tissue sarcomas and osteosarcomas were the most prevalent second cancers (standardized incidence ratio 179.35 compared to the German population). CONCLUSIONS: Second cancers remain a major concern in heritable retinoblastoma survivors. Consistent with previous reports, radiotherapy increased second cancer incidence and influenced type and localization. However, chemotherapy was the strongest risk factor for second malignancies outside the periorbital region. Our results provide screening priorities during life-long oncological follow-up based on the curative therapy the patient has received and emphasize the need for less-detrimental therapies for children with heritable retinoblastoma.
BACKGROUND: Survivors of heritable retinoblastoma carry a high risk to develop second cancers. Eye-preserving radiotherapy raises this risk, while the impact of chemotherapy remains less defined. PROCEDURE: This population-based study characterizes the impact of all treatment modalities on second cancers incidence and type after retinoblastoma treatment in Germany. Data on second cancer incidence in 648 patients with heritable retinoblastoma treated between 1940 and 2008 at the German national reference center for retinoblastoma were analyzed to identify associations with treatment. RESULTS: The cumulative incidence ratio (per 1,000 person years) of second cancers was 8.6 (95% confidence interval 7.0-10.4). Second cancer incidence was influenced by type of retinoblastoma treatment but not by the year of diagnosis or by sex. Radiotherapy and systemic chemotherapy increased the incidence of second cancers (by 3.0- and 1.8-fold, respectively). While radiotherapy was specifically associated with second cancers arising within the periorbital region in the previously irradiated field, chemotherapy was the strongest risk factor for second cancers in other localizations. Soft tissue sarcomas and osteosarcomas were the most prevalent second cancers (standardized incidence ratio 179.35 compared to the German population). CONCLUSIONS: Second cancers remain a major concern in heritable retinoblastoma survivors. Consistent with previous reports, radiotherapy increased second cancer incidence and influenced type and localization. However, chemotherapy was the strongest risk factor for second malignancies outside the periorbital region. Our results provide screening priorities during life-long oncological follow-up based on the curative therapy the patient has received and emphasize the need for less-detrimental therapies for children with heritable retinoblastoma.
Authors: Emily S Tonorezos; Danielle Novetsky Friedman; Dana Barnea; Machteld I Bosscha; Guillermo Chantada; Charlotte J Dommering; Pim de Graaf; Ira J Dunkel; Armida W M Fabius; Jasmine H Francis; Mary-Louise C Greer; Ruth A Kleinerman; Wijnanda A Kors; Suzanne Laughlin; Annette C Moll; Lindsay M Morton; Petra Temming; Margaret A Tucker; Flora E van Leeuwen; Michael F Walsh; Kevin C Oeffinger; David H Abramson Journal: Ophthalmology Date: 2020-05-15 Impact factor: 12.079
Authors: Norbert Bornfeld; Eva Biewald; Sebastian Bauer; Petra Temming; Dietmar Lohmann; Michael Zeschnigk Journal: Dtsch Arztebl Int Date: 2018-02-16 Impact factor: 5.594
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