title: Current knowledge and future research directions in treatment-related second primary malignancies.
abstract: Currently, 17-19% of all new primary malignancies occur in survivors of cancer, causing substantial morbidity and mortality. Research has shown that cancer treatments are important contributors to second malignant neoplasm (SMN) risk. In this paper we summarise current knowledge with regard to treatment-related SMNs and provide recommendations for future research. We address the risks associated with radiotherapy and systemic treatments, modifying factors of treatment-related risks (genetic susceptibility, lifestyle) and the potential benefits of screening and interventions. Research priorities were identified during a workshop at the 2014 Cancer Survivorship Summit organised by the European Organisation for Research and Treatment of Cancer. Recently, both systemic cancer treatments and radiotherapy approaches have evolved rapidly, with the carcinogenic potential of new treatments being unknown. Also, little knowledge is available about modifying factors of treatment-associated risk, such as genetic variants and lifestyle. Therefore, large prospective studies with biobanking, high quality treatment data (radiation dose-volume, cumulative drug doses), and data on other cancer risk factors are needed. International collaboration will be essential to have adequate statistical power for such investigations. While screening for SMNs is included in several follow-up guidelines for cancer survivors, its effectiveness in this special population has not been demonstrated. Research into the pathogenesis, tumour characteristics and survival of SMNs is essential, as well as the development of interventions to reduce SMN-related morbidity and mortality. Prediction models for SMN risk are needed to inform initial treatment decisions, balancing chances of cure and SMNs and to identify high-risk subgroups of survivors eligible for screening.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Morton
authors.affiliation: The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Swerdlow
authors.affiliation: Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Schaapveld
authors.affiliation: European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
authors.forename: Safaa
authors.initials: S
authors.lastname: Ramadan
authors.affiliation: Radiation Medicine Program, Princess Margaret Hospital, University Health Network, and Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David C
authors.initials: DC
authors.lastname: Hodgson
authors.affiliation: The University of Manchester and The Christie National Health Service Foundation Trust, Manchester, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Radford
authors.affiliation: Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
keywords: Chemotherapy; Multiple primary malignancies or multiple primary neoplasms; Radiotherapy; Treatment-induced