ESMO 2017-RAI USE IN THYROID CANCER AND RISK OF SECOND CANCER

Acute myeloid leukaemia (AML) is more likely to occur in patients treated with surgery plus radioactive iodine (RAI) as opposed to patients receiving just surgery for well-differentiated thyroid cancer (WDTC). Furthermore, patients developing AML after successful RAI therapy for WDTC had a far poorer prognosis than patients treated for WDTC that did not develop AML, and also compared to patients with de novo AML, with no prior history of cancer or anti-cancer treatment.

Findings from a population-based study were presented during the ESMO 2017, the Annual Congress of the European Society for Medical Oncology in Madrid, Spain.

Although it was known that the risk of developing leukaemia is increased following radiation and RAI treatment for WDTC, the risk of AML following RAI treatment in WDTC survivors had not been fully characterised, according to Remco J. Molenaar, Medical Oncology, Academic Medical Centre (AMC) in Amsterdam, Netherlands.

Dr. Molenaar and colleagues reviewed all 18 registries contained in the Surveillance Epidemiology and End Results (SEER) database for WDTC cases treated solely with surgery or by surgery followed by RAI for this population-based study. The risk dynamics of developing AML in WDTC patients and the association of AML to RAI was also assessed. Case-control studies were used to investigate the clinical outcome of AML occurring de novo or following WDTC diagnoses and treatment.

Increased risk of AML in patients treated with RAI for thyroid cancer

The researchers identified 148,215 patients who were diagnosed with WDTC from 1973 to 2014, of whom 55% were treated with surgery alone and 45% received surgery plus RAI for WDTC.

A median follow-up of 4.3 person years (interquartile range 1.9 to 7.4 years) disclosed that AML occurred in 44 patients after surgery compared to 56 patients receiving surgery plus RAI.

A further comparison to the background rates in the general population showed that patients receiving surgery plus RAI had an increased risk of developing AML (relative risk [RR] 5.6, 95% confidence interval [CI] 3.8, 8.1; p< 0.0001) compared with the background population after correcting for age, sex and year of WDTC diagnosis. This risk peaked within the first three years following RAI and subsequently regressed to baseline rates.

In multivariate analysis that corrected for sex and the WDTC tumour size, 3 variables including RAI emerged as independent prognostic factors for AML development. Increased risk of AML associated with patient age HR 1.03; 95% CI 1.02, 1.05 (p< 0.001), WDTC tumour stage, HR 1.36; 95% CI 1.04, 1.79 (p = 0.03), and receiving RAI treatment for WDTC as compared with thyroidectomy alone, HR 1.38; 95% CI 1.09, 1.75 (p = 0.007).

Prognosis is significantly poorer both in WDTC patients who develop AML following RAI compared to those who do not, and compared to patients with spontaneous AML development

Case-control analyses revealed that WDTC patients developing AML after surgery plus RAI survived one-third as long as matched control patients that were successfully treated for WDTC but did not develop AML; median overall survival (OS) was 7.4 years versus24.4 years, respectively (p< 0.0001).

In addition, patients that were diagnosed with AML after RAI treatment for WDTC had a significantly worse prognosis and demonstrated median OS of just 1.2 years compared to 3.5 years in patients with AML that occurred spontaneously (p= 0.004).

Conclusions

The investigators concluded that the rates of AML in WDTC survivors are likely to continue to rise, due to the increasing incidence of WDTC, the young ages at which most WDTC diagnosis are made and the otherwise excellent survival of patients with WDTC.

Furthermore, they found that RAI treatment associated with an increased risk of developing AML and patients with RAI-related AML had a poorer prognosis for survival that was similar to survival seen in patients developing therapy-related AML (t-AML) that occurs following radiotherapy or chemotherapy.

Tim Somervaille of the Cancer Research UK Manchester Institute, Manchester, UK who discussed the study results said that it is well established that prior chemotherapy or radiotherapy increases risk of secondary AML. Relative risk increases according to the type and dose of therapy (e.g. 2-6-fold in various breast cancer studies). Risk is greater with larger doses of chemotherapy, larger portal of radiation encompassing active bone marrow, stem cell stress after autologous transplant, use of G-CSF. Current study from Molenaar and colleagues provides more information with a systematic approach using registry data: therapy related AML after RAI is rare (1/1000) but there is 1.8-fold increase in relative risk. The study will enable better counselling of patients and redaction in numbers of patients having unnecessary RAI for well differentiated thyroid cancer.