Do Children With Spinal Deformity Who Have Metal Implants and Frequent Exposure to X-Rays Increase Their Risk of Cancer?

Peter J. Cundy, MBBS, FRACS; Kamalesh Venugopal, PhD, BSc; Georgia Antoniou, BSc (Hons); Francis Brooks, MBChB, FRCS; Brian J. C. Freeman, MB, BCh, BAO, DM, FRCS, FRACS, FAOrthA; Katina D'Onise, MBBS, MPH, PhD, FAFPHM

Disclosures

Spine. 2020;45(17):1200-1207. 

In This Article

Abstract and Introduction

Abstract

Study Design: Spinal surgery cohort.

Objective: The authors assess the risk of cancer in children who have undergone frequent radiographs and have metal implants for the treatment of spinal deformity.

Summary of Background Data: Concerns have been raised regarding the cancer risk to children exposed to repeated radiological examinations as part of routine surveillance to monitor progression of spinal deformity. Additionally, there are reports of increased cancer risk in adults having joint replacement with metal implants causing raised metal ion levels in the blood.

Methods: A large number of consecutive children undergoing instrumented spinal surgery since 1979 were examined for their development of malignancy. High quality data on all invasive cancers from the South Australian Cancer Registry and deaths were linked to the spinal surgery cohort with the calculation of standardized incidence ratios (SIRs) using the Quinquinquennium method.

Results: The study cohort was formed by 865 children. The average follow-up time from date of surgery to either death or censoring date was 18 years with a maximum of 36 years. A total of 15,921 person years were examined. There was no increased rate of cancer in these patients. For the total cohort, the SIR was 1.00 (95% confidence interval [CI] 0.50–1.79). For females the SIR was 0.83 (95% CI 0.33–1.70) and for males the SIR was 1.33 (95% CI 0.36–3.40). The male SIR reflected an expected cancer incidence of three cases, when four cases were observed, and was not statistically significant.

Conclusion: This study has found that radiation exposure and possible exposure to circulating metal ions as a result of routine instrumented spine surgery in children since 1979 is not associated with an increased risk of cancer in up to 36 years of follow up.

Level of Evidence: 2

Introduction

Surgery for children with scoliosis has occurred since the 1950s and is commonly accepted as a safe and effective treatment. Invariably it requires frequent radiation exposure (preoperative imaging for several years, intraoperative and postoperative radiographs for many years of follow-up) with retention of the metal implants (rods, hooks, and screws) remaining in-situ for the remainder of the patient's life. Both radiation exposure and metal implants have been cited as increasing the risk of cancer. The effects of radiation are well known, with published evidence suggesting an increased risk of cancer secondary to radiation exposure in the pediatric spinal deformity age group. Nash et al[1] found an increase of 7.5% for carcinogenic risk overall, with a 110% increased risk of breast cancer in 13 female patients with adolescent idiopathic scoliosis (AIS). A large study of 5573 female patients diagnosed with scoliosis in the years 1912 to 1965 in the USA, concluded an increased risk of breast cancer from iatrogenic radiation exposure, but emphasized potential confounding factors of radiation dose and severity of disease.[2] A recent non-controlled study from Denmark suggested a five times increased overall cancer rate in 215 AIS patients with an estimate of the radiation dose received.[3] Hoffman et al[4] reported from a study of patients treated between 1935 and 1965 with an average period of 26 years of observation, 11 cases of breast cancer compared with 6 expected (standardized incidence ratios [SIR] = 1.82, 90% CI = 1.0–3.0) and reported increased risk with time and radiation dose. There are also studies that have examined radiation exposure in children independent of scoliosis surgery. Mathews et al[5] found that the exposure in childhood to radiation by computed tomography (CT) scanning was associated with an increased risk of cancer incidence by 9.38 per 100,000. This group found that there was an increased risk in solid organ and lymphoid cancers, myelodysplasia and leukaemia, with an excess of 608 (0.9%) cases in 680,211 study patients.

There is some evidence of an association between metal implants used in Total Joint Replacements (TJR) and an increased cancer risk.[6–9] It is thought to be due to exposure of circulating metal ions however some series indicate no increased risk. Concern has been raised in relation to cancer risk, cardiac function and neurological effects after total hip replacement using metal-on-metal bearing surfaces with measurement of high blood levels of cobalt and chromium. The reported metal ion levels in metal-on-metal hip replacements are commonly in the order of 100 times the levels compared with scoliosis implant surgery where two to four parts per billion (ppb) are seen. Studies in various large metal-on-metal hip arthroplasty populations have suggested that there may be an increased risk of malignancies, in particular hematological and renal but other studies of total joint arthroplasty suggest otherwise.[10,11] Pediatric spinal instrumentation traditionally used medical grade stainless steel (316L) and more recently utilizes other metals such as titanium and cobalt–chrome alloys. Some of the authors in this current study have published their results on metal ion levels after pediatric spine surgery.[12–14] Factors contributing to degradation have been considered including applied stress, fretting, micro-motion, and chemical dissolution. Macroscopic evidence of degradation in explanted posterior stainless steel spinal implants has been reported in over 50% of cases.[15] These findings are potentially important for cancer risk given the evidence that inhaled chromium has been associated with an increased risk of lung cancer, in particular for people who work with chromium.[16] Further, titanium has been identified as a Group 2B human carcinogen, suggesting that it may pose a cancer risk in children who have titanium spinal implants.[17] A recent study summarized the potential effects of heavy metals on the human genome particularly on the transposable elements (TE) of genes. These areas were once thought to be "junk DNA" regions. However, changes in TE sequences are thought to affect genetic stability in germ-lines and somatic cells such that the behaviors of cancer are altered. This concept provides a necessary link for environmental causes of cancer, such as smoking and excess alcohol. Various heavy metals are implicated in affecting TE sequences, notably nickel and cadmium. Cadmium has been cited as a risk for breast cancer due to an oestrogen-like effect on receptor cells (metallo-oestrogen).[18]

The long-term consequences of retained metal implants in young patients are unclear. This study was designed to specifically assess the risk of cancer in patients who had exposure to both radiation and spinal implants during childhood.

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