Incidence of second primary cancers among survivors of childhood cancer: A population‐based study, Osaka, Japan, 1975–2015

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Abstract

Second primary cancer (SPC) is one of the most life‐threatening late effects of childhood cancers. We investigated the incidence and survival outcomes of SPC in childhood cancer patients in Japan. Data were obtained from the population‐based Osaka Cancer Registry. Individuals diagnosed with cancer at age 0–14 years during 1975–2014 and survived 2 months or longer were followed through December 2015. The risk of developing SPC was assessed with standardized incidence ratio (SIR), excess absolute risk (EAR, per 100,000 person‐years), and cumulative incidence. Multivariable Poisson regression analysis was carried out to assess relative risks of SPC by treatment method. Survival analysis was undertaken using the Kaplan–Meier method. Of 7229 childhood cancer survivors, 101 (1.4%) developed SPC after a median of 11.6 years. Overall SIR was 5.0, which corresponded with 84.3 EAR. The cumulative incidence was 0.9%, 2.1%, and 3.4% at 10, 20, and 30 years, respectively. Among all SPCs, the type that contributed most to the overall burden was cancers in the central nervous system (EAR = 28.0) followed by digestive system (EAR = 15.1), thyroid (EAR = 8.3), and bones and joints (EAR = 7.8); median latency ranged from 2.0 years (lymphomas) to 26.6 years (skin cancers). Patients treated with radiotherapy alone were at a 2.58‐fold increased risk of developing SPC compared to those who received neither chemotherapy nor radiotherapy. Among patients who developed SPCs, 5‐year and 10‐year survival probabilities after SPC diagnosis were 61.7% and 52.0%, respectively. Risk‐based long‐term follow‐up planning is essential to inform survivorship care and help reduce the burden of SPCs in childhood cancer survivors.

Abstract

We investigated the incidence and survival outcomes of SPC in childhood cancer patients in Japan using the population‐based Osaka Cancer Registry. During 1975‐2015, childhood cancer patients who survived ≥2 months were at a five‐fold increased risk of developing a new cancer relative to the general population of Osaka with a median of 11.6 years of latency. Risk‐based long‐term follow‐up planning is essential to inform survivorship care and help reduce the burden of SPCs in childhood cancer survivors.

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International incidence of childhood cancer, 2001–10: a population-based registry study

Eva Steliarova-Foucher, Murielle Colombet, Lynn A. G. Ries … (2017)

Summary Background Cancer is a major cause of death in children worldwide, and the recorded incidence tends to increase with time. Internationally comparable data on childhood cancer incidence in the past two decades are scarce. This study aimed to provide internationally comparable local data on the incidence of childhood cancer to promote research of causes and implementation of childhood cancer control. Methods This population-based registry study, devised by the International Agency for Research on Cancer in collaboration with the International Association of Cancer Registries, collected data on all malignancies and non-malignant neoplasms of the CNS diagnosed before age 20 years in populations covered by high-quality cancer registries with complete data for 2001–10. Incidence rates per million person-years for the 0–14 years and 0–19 years age groups were age-adjusted using the world standard population to provide age-standardised incidence rates (WSRs), using the age-specific incidence rates (ASR) for individual age groups (0–4 years, 5–9 years, 10–14 years, and 15–19 years). All rates were reported for 19 geographical areas or ethnicities by sex, age group, and cancer type. The regional WSRs for children aged 0–14 years were compared with comparable data obtained in the 1980s. Findings Of 532 invited cancer registries, 153 registries from 62 countries, departments, and territories met quality standards, and contributed data for the entire decade of 2001–10. 385 509 incident cases in children aged 0–19 years occurring in 2·64 billion person-years were included. The overall WSR was 140·6 per million person-years in children aged 0–14 years (based on 284 649 cases), and the most common cancers were leukaemia (WSR 46·4), followed by CNS tumours (WSR 28·2), and lymphomas (WSR 15·2). In children aged 15–19 years (based on 100 860 cases), the ASR was 185·3 per million person-years, the most common being lymphomas (ASR 41·8) and the group of epithelial tumours and melanoma (ASR 39·5). Incidence varied considerably between and within the described regions, and by cancer type, sex, age, and racial and ethnic group. Since the 1980s, the global WSR of registered cancers in children aged 0–14 years has increased from 124·0 (95% CI 123·3–124·7) to 140·6 (140·1–141·1) per million person-years. Interpretation This unique global source of childhood cancer incidence will be used for aetiological research and to inform public health policy, potentially contributing towards attaining several targets of the Sustainable Development Goals. The observed geographical, racial and ethnic, age, sex, and temporal variations require constant monitoring and research. Funding International Agency for Research on Cancer and the Union for International Cancer Control.

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Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study.

Wendy Leisenring, Sue Hammond, Michaela S. Donaldson … (2010)

The occurrence of subsequent neoplasms has direct impact on the quantity and quality of life in cancer survivors. We have expanded our analysis of these events in the Childhood Cancer Survivor Study (CCSS) to better understand the occurrence of these events as the survivor population ages. The incidence of and risk for subsequent neoplasms occurring 5 years or more after the childhood cancer diagnosis were determined among 14,359 5-year survivors in the CCSS who were treated from 1970 through 1986 and who were at a median age of 30 years (range = 5-56 years) for this analysis. At 30 years after childhood cancer diagnosis, we calculated cumulative incidence at 30 years of subsequent neoplasms and calculated standardized incidence ratios (SIRs), excess absolute risks (EARs) for invasive second malignant neoplasms, and relative risks for subsequent neoplasms by use of multivariable Poisson regression. Among 14,359 5-year survivors, 1402 subsequently developed 2703 neoplasms. Cumulative incidence at 30 years after the childhood cancer diagnosis was 20.5% (95% confidence interval [CI] = 19.1% to 21.8%) for all subsequent neoplasms, 7.9% (95% CI = 7.2% to 8.5%) for second malignant neoplasms (excluding nonmelanoma skin cancer), 9.1% (95% CI = 8.1% to 10.1%) for nonmelanoma skin cancer, and 3.1% (95% CI = 2.5% to 3.8%) for meningioma. Excess risk was evident for all primary diagnoses (EAR = 2.6 per 1000 person-years, 95% CI = 2.4 to 2.9 per 1000 person-years; SIR = 6.0, 95% CI = 5.5 to 6.4), with the highest being for Hodgkin lymphoma (SIR = 8.7, 95% CI = 7.7 to 9.8) and Ewing sarcoma (SIR = 8.5, 95% CI = 6.2 to 11.7). In the Poisson multivariable analysis, female sex, older age at diagnosis, earlier treatment era, diagnosis of Hodgkin lymphoma, and treatment with radiation therapy were associated with increased risk of subsequent neoplasm. As childhood cancer survivors progress through adulthood, risk of subsequent neoplasms increases. Patients surviving Hodgkin lymphoma are at greatest risk. There is no evidence of risk reduction with increasing duration of follow-up.

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Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis

Satoshi Watanabe, Junta Tanaka, Takeshi Ota … (2011)

Background Gefitinib was the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Few treatment options are available for NSCLC patients who have responded to gefitinib treatment and demonstrated tumor progression. The present study was conducted to evaluate the efficacy and toxicity of the 2nd EGFR-TKI administration. Methods We retrospectively analyzed 11 patients who had obtained a partial response (PR) or stable disease (SD) with gefitinib treatment and were re-treated with EGFR-TKI after failure of the initial gefitinib treatment. Results Three patients (27%) were treated with gefitinib as the 2nd EGFR-TKI, and 8 patients (73%) received erlotinib. Only one patient (9%) showed PR, 7 (64%) achieved SD, and 3 (27%) had progressive disease. The disease control rate was 73% (95% CI, 43% - 91%) and the median progression-free survival was 3.4 months (95% CI, 2 - 5.2). The median overall survival from the beginning of the 2nd EGFR-TKI and from diagnosis were 7.3 months (95% CI, 2.7 - 13) and 36.7 months (95% CI, 23.6 - 43.9), respectively. No statistical differences in PFS or OS were observed between gefitinib and erlotinib as the 2nd EGFR-TKI (PFS, P = 0.23 and OS, P = 0.052). The toxicities associated with the 2nd EGFR-TKI were generally acceptable and comparable to those observed for the initial gefitinib therapy. Conclusions Our results indicate that a 2nd EGFR-TKI treatment can be an effective treatment option for gefitinib responders.

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Author and article information

Contributors

Satomi Odani:

ORCID: https://orcid.org/0000-0002-6263-4952

satomi.odani@oici.jp

Journal

Journal ID (nlm-ta): Cancer Sci

Journal ID (iso-abbrev): Cancer Sci

Journal ID (doi): 10.1111/(ISSN)1349-7006

Journal ID (publisher-id): CAS

Title: Cancer Science

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 1347-9032

ISSN (Electronic): 1349-7006

Publication date (Electronic): 23 November 2022

Publication date Collection: March 2023

Volume: 114

Issue: 3 ( doiID: 10.1111/cas.v114.3 )

Pages: 1142-1153

Affiliations

[ ¹ ] Cancer Control Center Osaka International Cancer Institute Osaka Japan

[ ² ] Graduate School of Medicine Osaka University Osaka Japan

[ ³ ] Department of Hematology/Oncology Osaka Women's and Children's Hospital Osaka Japan

[ ⁴ ] Department of Pediatrics Osaka International Cancer Institute Osaka Japan

[ ⁵ ] Department of Pediatric Hematology and Oncology Osaka City General Hospital Osaka Japan

Author notes

[*] [* ] Correspondence

Satomi Odani, Cancer Control Center, Osaka International Cancer Institute, 3‐1‐69 Chuoku Otemae, Osaka 541‐8567, Japan.

Email: satomi.odani@ 123456oici.jp

Author information

Satomi Odani https://orcid.org/0000-0002-6263-4952

Kayo Nakata https://orcid.org/0000-0001-9782-8637

Toshitaka Morishima https://orcid.org/0000-0002-0747-3287

Junich Hara https://orcid.org/0000-0002-6798-1558

Article

Publisher ID: CAS15640 Other ID: CAS-OA-1333-2022.R2

DOI: 10.1111/cas.15640

PMC ID: 9986077

PubMed ID: 36345911

SO-VID: 52df675a-ee52-4f8f-9991-fa97534f421f

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

History

Date revision received : 20 October 2022

Date received : 21 June 2022

Date accepted : 27 October 2022

Page count

Figures: 3, Tables: 4, Pages: 12, Words: 6944

Funding

Funded by: Japan Society for the Promotion of Science , doi 10.13039/501100001691;

Award ID: JP20K18952

Award ID: JP22K10548

Funded by: Ministry of Health, Labour and Welfare , doi 10.13039/501100003478;

Award ID: 20EA1026

Award ID: H30‐Gantaisaku‐Ippan‐009

Custom metadata

source-schema-version-number 2.0

cover-date March 2023

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.5 mode:remove_FC converted:05.03.2023

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cancer registry,childhood cancer,population‐based analysis,second primary cancer

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cancer registry, childhood cancer, population‐based analysis, second primary cancer

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Incidence of second primary cancers among survivors of childhood cancer: A population‐based study, Osaka, Japan, 1975–2015

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Most cited references 53

International incidence of childhood cancer, 2001–10: a population-based registry study

Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study.

Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis

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