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Original Research |

Screening and Surveillance for Second Malignant Neoplasms in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Paul Craig Nathan, MD, MSc; Kirsten Kimberlie Ness, PT, PhD; Martin Christopher Mahoney, MD, PhD; Zhenghong Li, MSc; Melissa Maria Hudson, MD; Jennifer Sylene Ford, PhD; Wendy Landier, RN, MSN, CPNP; Marilyn Stovall, PhD; Gregory Thomas Armstrong, MD, MSCE; Tara Olive Henderson, MD, MPH; Leslie L. Robison, PhD; and Kevin Charles Oeffinger, MD
[+] Article and Author Information

From the Hospital for Sick Children, Toronto, Ontario, Canada; St. Jude Children's Research Hospital, Memphis, Tennessee; Roswell Park Cancer Institute, Buffalo, and Memorial Sloan-Kettering Cancer Center, New York, New York; City of Hope, Duarte, California; The University of Texas M.D. Anderson Cancer Center, Houston, Texas; and University of Chicago Comer Children's Hospital, Chicago, Illinois.


Acknowledgment: The CCSS is a collaborative, multi-institutional project, funded as a resource by the National Cancer Institute. The cohort was assembled through the efforts of 26 participating clinical research centers in the United States and Canada. Information on how to access and use the CCSS resource is available at http://ccss.stjude.org.

Grant Support: By the National Cancer Institute, National Institutes of Health (grant U24-CA-55727) to Dr. Robison and by the American Lebanese Syrian Associated Charities.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-0953.

Reproducible Research Statement:Study protocol and statistical code: Available from Dr. Nathan (e-mail, paul.nathan@sickkids.ca). Data set: Available from Dr. Nathan. See www.stjude.org/ccss for description of data utilization procedures.

Requests for Single Reprints: Paul Craig Nathan, MD, MSc, The Hospital for Sick Children, Division of Haematology/Oncology, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada; e-mail, paul.nathan@sickkids.ca.

Current Author Addresses: Dr. Nathan: The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.

Drs. Ness, Hudson, Armstrong, and Robison and Mr. Li: St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105.

Dr. Mahoney: Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263.

Drs. Ford and Oeffinger: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065.

Ms. Landier: City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010.

Dr. Stovall: The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Dr. Henderson: Comer Children's Hospital at the University of Chicago, 5721 South Maryland Avenue, Chicago, IL 60637.

Author Contributions: Conception and design: P.C. Nathan, K.K. Ness, M.M. Hudson, W. Landier, G.T. Armstrong, L.L. Robison, K.C. Oeffinger.

Analysis and interpretation of the data: P.C. Nathan, K.K. Ness, M.C. Mahoney, Z. Li, J.S. Ford, W. Landier, M. Stovall, T.O. Henderson, L.L. Robison, K.C. Oeffinger.

Drafting of the article: P.C. Nathan, K.K. Ness, J.S. Ford, M. Stovall, G.T. Armstrong, T.O. Henderson, L.L. Robison, K.C. Oeffinger.

Critical revision of the article for important intellectual content: P.C. Nathan, K.K. Ness, M.C. Mahoney, M.M. Hudson, J.S. Ford, W. Landier, T.O. Henderson, L.L. Robison, K.C. Oeffinger.

Final approval of the article: P.C. Nathan, K.K. Ness, M.C. Mahoney, M.M. Hudson, J.S. Ford, W. Landier, M. Stovall, G.T. Armstrong, T.O. Henderson, L.L. Robison, K.C. Oeffinger.

Provision of study materials or patients: M.M. Hudson, G.T. Armstrong, L.L. Robison.

Statistical expertise: K.K. Ness, Z. Li, M. Stovall, L.L. Robison.

Obtaining of funding: L.L. Robison.

Administrative, technical, or logistic support: L.L. Robison.

Collection and assembly of data: M. Stovall, G.T. Armstrong, T.O. Henderson, L.L. Robison.


Ann Intern Med. 2010;153(7):442-451. doi:10.7326/0003-4819-153-7-201010050-00007
Text Size: A A A

Background: Survivors of childhood cancer may develop a second malignant neoplasm during adulthood and therefore require regular surveillance.

Objective: To examine adherence to population cancer screening guidelines by survivors at average risk for a second malignant neoplasm and adherence to cancer surveillance guidelines by survivors at high risk for a second malignant neoplasm.

Design: Retrospective cohort study.

Setting: The Childhood Cancer Survivor Study (CCSS), a 26-center study of long-term survivors of childhood cancer that was diagnosed between 1970 and 1986.

Patients: 4329 male and 4018 female survivors of childhood cancer who completed a CCSS questionnaire assessing screening and surveillance for new cases of cancer.

Measurements: Patient-reported receipt and timing of mammography, Papanicolaou smear, colonoscopy, or skin examination was categorized as adherent to the U.S. Preventive Services Task Force guidelines for survivors at average risk for breast or cervical cancer or the Children's Oncology Group guidelines for survivors at high risk for breast, colorectal, or skin cancer as a result of cancer therapy.

Results: In average-risk female survivors, 2743 of 3392 (80.9%) reported having a Papanicolaou smear within the recommended period, and 140 of 209 (67.0%) reported mammography within the recommended period. In high-risk survivors, rates of recommended mammography among women were only 241 of 522 (46.2%) and the rates of colonoscopy and complete skin examinations among both sexes were 91 of 794 (11.5%) and 1290 of 4850 (26.6%), respectively.

Limitations: Data were self-reported. Participants in the CCSS are a selected group of survivors, and their adherence may not be representative of all survivors of childhood cancer.

Conclusion: Female survivors at average risk for a second malignant neoplasm show reasonable rates of screening for cervical and breast cancer. However, surveillance for new cases of cancer is very low in survivors at the highest risk for colon, breast, or skin cancer, suggesting that survivors and their physicians need education about their risks and recommended surveillance.

Primary Funding Source: The National Cancer Institute, National Institutes of Health, and the American Lebanese Syrian Associated Charities.

Figures

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Figure.
Adherence to screening guidelines for mammography and Papanicolaou smear by female survivors at average risk for breast or cervical cancer, and to surveillance guidelines for mammography (women only) and colonoscopy (both sexes) by survivors at increased risk for breast or colorectal cancer.
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Screening for Thyroid Carcinoma in Adult Survivors of Childhood Cancer
Posted on October 18, 2010
Enrico Brignardello
No Affiliation
Conflict of Interest: None Declared

TO THE EDITOR: in their interesting paper, Nathan and colleagues focus on the very poor adherence to recommended surveillance found in childhood cancer survivors at the highest risk for colon, breast or skin cancer. We completely agree with the Authors' conclusion, suggesting that survivors and their physicians need education about their risks and proper follow-up. Survivors have also an increased risk for other second malignancies, such as thyroid cancer, for which the screening in general population is not recommended. We are aware that ultrasound screening for thyroid cancer in general population is not cost-effective and may lead to unnecessary surgery. Nevertheless, guidelines for diagnosis and management of thyroid nodules suggest to screen by ultrasound patients at high risk for the development of thyroid malignancies (1). According to this indication, in the setting of a long-term follow-up unit for childhood cancer survivors, we routinely perform thyroid ultrasound in all the patients who previously received radiotherapy to head, neck or upper thorax (2). By doing so, among the 172 survivors (males = 88; females = 84) previously treated by radiotherapy involving thyroid gland we diagnosed 10 thyroid carcinomas (F=3 ; M=7), a much higher number than expected (3). Median elapsed time between radiation therapy and thyroid cancer diagnosis was 20.7 years (range 14.1- 27.9). In all cases the histological diagnosis was papillary carcinoma. Five of these thyroid carcinomas were not palpable and they were detected only by ultrasound. However, the histological examination showed nodal metastases in eight of them, one of them even with lung metastases. Currently available guidelines for long term follow-up of childhood cancer survivors recommend only an annual physical examination of the thyroid gland in patients at high risk for thyroid cancer (4). It is because thyroid carcinomas usually progress very slowly, so that the clinical relevance of an earlier diagnosis is thought to be little. Nevertheless, radiation-induced thyroid carcinoma has been suspected to be more aggressive and an early detection could improve the outcome in this specific subset of young patients (5). Thus we believe that, in survivors treated with radiation therapy involving the thyroid, ultrasound screening for thyroid carcinoma would be worthwhile. Our findings also suggest that the prevalence of radiation-induced thyroid cancer in childhood cancer survivors might be much higher than that measured by epidemiological studies based on patients self-report.

References

1. Gharib H, Papini E, Paschke R, Duick DS, Valcalvi R, Hegedus L et al; AACE, AME, ETA Medical Guidelines for Clinical Practice for the Diagnosis and Menagement of thyroid nodules. J Endocrinol Invest 2010; 33: 1-50.

2. Brignardello E, Corrias A, Isolato G, Palestini N, Cordero di Montezemolo L, Fagioli F et al; Ultrasound Screening for Thyroid Carcinoma in Childhood Cancer Survivors: a case series. J Clin Endocrinol Metab 2008; 93: 4840-4843.

3. Bhatti , Veiga LH, Ronckers CX, Sigurdson AJ, Stovall M, Smith SA et al; Risk of Second Primary Thyroid Cancer after Radiotherapy for a Childhood Cancer in a Large Cohort Study: An Update from the Childhood Cancer Survivor Study. Radiat Res 2010; [in press]

4. Children's Oncology Group; Long Term Follow-up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers. Accessed at www.survivorshipguidelines.org on october 2010.

5. Bucci A, Shore-Freedman E, Gierlowsky T, Mihailescu D, Ron E, Schneider AB; Behaviour of small thyroid cancers found by screening radiation-exposed individuals. J Clin Endocrinol Metab 2001; 86:3711-3716.

Conflict of Interest:

None declared

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Summary for Patients

Cancer Screening Among Adults Who Have Survived Childhood Cancer

The summary below is from the full report titled “Screening and Surveillance for Second Malignant Neoplasms in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.” It is in the 5 October 2010 issue of Annals of Internal Medicine (volume 153, pages 442-451). The authors are P.C. Nathan, K.K. Ness, M.C. Mahoney, Z. Li, M.M. Hudson, J.S. Ford, W. Landier, M. Stovall, G.T. Armstrong, T.O. Henderson, L.L. Robison, and K.C. Oeffinger.

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