Second primary malignancy risk in thyroid cancer and matched patients with and without radioiodine therapy analysis from the observational health data sciences and informatics

Kim, Seok; Bang, Ji-In; Boo, Dachung; Kim, Borham; Choi, In Young; Ko, SooJeong; Yoo, Ie Ryung; Kim, Kwangsoo; Kim, Junmo; Joo, Young-Hwan; Ryoo, Hyun Gee; Paeng, Jin Chul; Park, Sungha; Jang, Woncheol; Kim, Byungwon; Chung, Yangha; Yang, Dong-Yoon; Yoo, Sooyoung; Lee, Ho-Young

doi:10.1007/s00259-022-05779-9

Cited by 16 publications

(10 citation statements)

References 23 publications

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“…However, breast cancer risk remains controversial and the above results have not been confirmed in a large and focused metanalysis of 200247 DTC patients treated with or without radioiodine [ 159 ]. Similarly, Kim et al [ 160 ] performed a propensity-score analysis on a wide retrospective multicenter sample of 24318 patients, including RAI-treated and non-RAI-treated subjects, concluding that there was an absence of significant risk of the occurrence of second tumors.…”

Section: Side Effects Of Raimentioning

confidence: 99%

Strategies for Radioiodine Treatment: What’s New

Sparano

Moog

Hadoux

et al. 2022

Cancers

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Radioiodine treatment (RAI) represents the most widespread and effective therapy for differentiated thyroid cancer (DTC). RAI goals encompass ablative (destruction of thyroid remnants, to enhance thyroglobulin predictive value), adjuvant (destruction of microscopic disease to reduce recurrences), and therapeutic (in case of macroscopic iodine avid lesions) purposes, but its use has evolved over time. Randomized trial results have enabled the refinement of RAI indications, moving from a standardized practice to a tailored approach. In most cases, low-risk patients may safely avoid RAI, but where necessary, a simplified protocol, based on lower iodine activities and human recombinant TSH preparation, proved to be just as effective, reducing overtreatment or useless impairment of quality of life. In pediatric DTC, RAI treatments may allow tumor healing even at the advanced stages. Finally, new challenges have arisen with the advancement in redifferentiation protocols, through which RAI still represents a leading therapy, even in former iodine refractory cases. RAI therapy is usually well-tolerated at low activities rates, but some concerns exist concerning higher cumulative doses and long-term outcomes. Despite these achievements, several issues still need to be addressed in terms of RAI indications and protocols, heading toward the RAI strategy of the future.

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Section: Side Effects Of Raimentioning

confidence: 99%

Strategies for Radioiodine Treatment: What’s New

Sparano

Moog

Hadoux

et al. 2022

Cancers

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“…Discordant data regarding the development of SPM in patients treated with RAI have been reported [7][8][9][10][11][12][13][14][15][16][17][18][19][20]27]. Undeniably, the body of evidence provided by literature on this topic shows a wide heterogeneity in methods and results [7][8][9][10][11][12][13][14][15][16][17][18][19][20]27]. To date, the risk of developing SPM after an RAI cannot be excluded a priori, but it is expected to be low [10][11][12]17,18,20].…”

Section: Discussionmentioning

confidence: 99%

“…Undeniably, the body of evidence provided by literature on this topic shows a wide heterogeneity in methods and results [7][8][9][10][11][12][13][14][15][16][17][18][19][20]27]. To date, the risk of developing SPM after an RAI cannot be excluded a priori, but it is expected to be low [10][11][12]17,18,20].…”

Section: Discussionmentioning

confidence: 99%

“…Second primary malignancies (SPM), described as any primary, not synchronous, malignancy arising in a different anatomical district with confirmed histological diagnosis, is reported in patients with DTC [5]. Actually, different incidences of SPM have been previously reported, ranging from 0.5% to 22% [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Moreover, several factors can influence the incidence of SPM in patients with DTC.…”

Section: Introductionmentioning

confidence: 99%

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Second Primary Malignancies in Patients with Differentiated Thyroid Cancer after Radionuclide Therapy: A Retrospective Single-Centre Study

et al. 2022

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Second primary malignancies (SPM) are described as any primary, not synchronous, malignancy arising in a different anatomical district, with confirmed histological diagnosis. Age at diagnosis, previous non-thyroidal primary malignancy, and radioactive iodine (RAI) therapy have been proposed as independent risk factors for SPM. RAI therapy is a standard treatment for moderate-high risk differentiated thyroid cancer (DTC), and its effect on the development of SPM has become a critical topic in DTC treatment. The purpose of this retrospective single-center study was to investigate the occurrence and the possible association of non-thyroidal SPM diagnosed after DTC and RAI therapy in a cohort of 1326 consecutive DTC patients referred at our Institution for RAI treatment from 1993 to 2009. Eighty-nine patients with ages ≤ 18 years at the time of DTC diagnosis or with a follow-up of ≤12 months were excluded from the final analysis. All patients underwent a complete clinical and hematological follow-up every 6 months for a minimum of 12 months. During follow-up (mean 89 ± 73 months), 25 patients (2%) had an SPM diagnosis (mean 133 ± 73 months). The most common site of the second malignancy was the breast, accounting for 32% of all SPM, followed by colon-rectal cancer (16%), leukemia, and gynecological and kidney cancer (4%). At Cox univariable regression analysis, age at DTC diagnosis (p < 0.001), age ≥55 years (p < 0.001) and follow-up duration (p < 0.004) were associated with SPM onset, while no significant association was observed with the administered activity of radioiodine. In conclusion, our data suggest that the older a person gets, the more sharply the likelihood of developing additional diseases, such as PMS, increases. Similarly, for follow-up, the more a patient is followed up clinically over time, the higher the risk of new diagnoses increases.

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“…Our proposed model focuses on pediatric cancer patient survivors, to propose a causative link between acute thymic involution and defective cancer immunoediting mechanisms leading to SPMs. Nevertheless, SPM development also occurs in non-pediatric patients, and similar mechanisms could also be relevant in these populations (41,(213)(214)(215)(216)(217)(218)(219)(220)(221). The pediatric cancer survivor paradigm was easier to discuss in our model, first because there are long-term follow-up epidemiological data that can be used as a better proof-of-concept (222-224), and second, because thymic functions are relatively stronger in childhood, as compared to other ages (201).…”

Section: Criticisms Of the Proposed Model And Future Repercussionsmentioning

confidence: 99%

A Proposed Link Between Acute Thymic Involution and Late Adverse Effects of Chemotherapy

Lagou

Anastasiadou²,

Karagiannis³

2022

Front. Immunol.

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Epidemiologic data suggest that cancer survivors tend to develop a protuberant number of adverse late effects, including second primary malignancies (SPM), as a result of cytotoxic chemotherapy. Besides the genotoxic potential of these drugs that directly inflict mutational burden on genomic DNA, the precise mechanisms contributing to SPM development are poorly understood. Cancer is nowadays perceived as a complex process that goes beyond the concept of genetic disease and includes tumor cell interactions with complex stromal and immune cell microenvironments. The cancer immunoediting theory offers an explanation for the development of nascent neoplastic cells. Briefly, the theory suggests that newly emerging tumor cells are mostly eliminated by an effective tissue immunosurveillance, but certain tumor variants may occasionally escape innate and adaptive mechanisms of immunological destruction, entering an equilibrium phase, where immunologic tumor cell death “equals” new tumor cell birth. Subsequent microenvironmental pressures and accumulation of helpful mutations in certain variants may lead to escape from the equilibrium phase, and eventually cause an overt neoplasm. Cancer immunoediting functions as a dedicated sentinel under the auspice of a highly competent immune system. This perspective offers the fresh insight that chemotherapy-induced thymic involution, which is characterized by the extensive obliteration of the sensitive thymic epithelial cell (TEC) compartment, can cause long-term defects in thymopoiesis and in establishment of diverse T cell receptor repertoires and peripheral T cell pools of cancer survivors. Such delayed recovery of T cell adaptive immunity may result in prolonged hijacking of the cancer immunoediting mechanisms, and lead to development of persistent and mortal infections, inflammatory disorders, organ-specific autoimmunity lesions, and SPMs. Acknowledging that chemotherapy-induced thymic involution is a potential risk factor for the emergence of SPM demarcates new avenues for the rationalized development of pharmacologic interventions to promote thymic regeneration in patients receiving cytoreductive chemotherapies.

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Second primary malignancy risk in thyroid cancer and matched patients with and without radioiodine therapy analysis from the observational health data sciences and informatics

Cited by 16 publications

References 23 publications

Strategies for Radioiodine Treatment: What’s New

Strategies for Radioiodine Treatment: What’s New

Second Primary Malignancies in Patients with Differentiated Thyroid Cancer after Radionuclide Therapy: A Retrospective Single-Centre Study

A Proposed Link Between Acute Thymic Involution and Late Adverse Effects of Chemotherapy

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