Table 1.
The burden of subsequent malignant neoplasms (SMNs) among adolescent and young adult cancer survivors by tumor group (n = 23).
| Reference | Cancer Type | Number of AYA Participants | Outcome Ascertainment |
Results |
|---|---|---|---|---|
| Mixed-Cancer Cohort | ||||
| Aben, 2012 [21] | Any primary malignancy except basal carcinomas of the skin | 23,161 | Netherlands Cancer Registry | At median follow-up time, 1.8% of AYAs developed subsequent cancers. |
| Henderson, 2012 [22] | First primary malignancy: leukemia, CNS malignancy, HL, NHL, neuroblastoma, soft-tissue sarcoma, kidney cancer or bone cancer. SMN: Sarcoma | 2487 | Self- or proxy-report questionnaire, and by searches of National Death Index data for US participants | 17 out of 2487 (0.7%) AYAs 15–20 developed a gastrointestinal SMN. |
| Zhang, 2012 [18] | Any primary malignancy | 1248 | Cohort linked to the population-based Netherlands Cancer Registry (post 1989) or the Dutch Pathology Registry (pre 1989), as well as hospital medical records | 62 SMNs were observed. Compared to the general population, SIR for the overall cohort was 3.0 (95% CI 2.3–3.8) with an associated AER of 1.9 per 1000 person-years. SIR for experiencing any type of SMN was 3.6 (95% CI 2.3–5.3) for males and 2.7 (95% CI 1.9–3.7) for females, with associated AERs of 1.9 and 2.0 per 1000 person-years, respectively. |
| Lee, 2016 [17] | First Primary: leukemia, lymphoma, germ cell tumors (testicular, ovarian), melanoma, thyroid, breast, sarcomas (soft tissue or bone). SMNs: Any cancer with malignant behavior excluding basal cell and cutaneous squamous cell carcinomas | 148,558 | British Columbia Cancer Registry | 7384 patients developed SMN after their original diagnosis. Compared to age- and gender-specific rates, the overall risk of an SMN was 1.6 (95% CI 1.55–1.62) times higher for AYAs (lower than for children, higher than for older adults). AER was 22.9 per 10,000 person-years for AYAs, which was higher than for children or older adults. |
| Teepen, 2017 [19] | Any primary malignancy | 401 | SEER | 9.6% of those 15-17 years at diagnosis developed a SMN (SIR: 3.3, 95% CI 2.2–4.9; Excess absolute risk [EAR] 25.9 per 10,000 person-years). The SIR for all solid tumors and hematologic malignancies were 3.7 (95% CI 2.4–5.5; EAR 25.9) and 4.1 (95% CI 2.1–7.4; EAR 2.4), respectively, compared to the general population. |
| Hayek, 2018 [23] | Any primary malignancy | 1765 | Cohort linked to the Israel National Cancer Registry | 75 SPNs were reported in the AYA age group, corresponding with a HR of 1.83 (95% CI 1.21, 2.75). |
| Bright, 2019 [24] | Breast, cervical, testicular, HL, NHL, melanoma, CNS (intracranial), colorectal, thyroid, soft–tissue sarcoma, ovarian, bladder, other female genital cancers, leukemia, and head and neck | 197,827 | Office for National Statistics (England) and Welsh Cancer Intelligence and Surveillance Unit, Public Health Wales | 12,321 subsequent primary neoplasms were diagnosed in 11,565 survivors, most of whom were survivors of breast cancer, cervical cancer, testicular cancer, and HL. |
| Chao, 2019 [25] | Any primary malignancy | 10,574 | Kaiser Permanente Southern California’s SEER-affiliated cancer registry and the California Cancer Registry | 622 AYA cancer survivors developed SMN (6.7 per 1000 person-years). Survivors faced 2.6-fold higher risk of developing SMN relative to a comparison cohort. |
| Fidler, 2018 [26] | First primary malignancy: All cancers. SMN: bone cancers. | 11,472 | (Varied by country) Population-based cancer registries, late effect clinics, questionnaires, medical records and hospital data, national mortality records, and health insurance registries, validated by pathology or diagnostic reports | Of 11,472 AYA survivors, 10 subsequent primary bone cancers were diagnosed during follow-up time, whereas 1.1 were expected. AYA survivors had an SIR of 9.0 (95% CI 4.3, 16.5) for developing subsequent bone cancers than expected in their age group. |
| Zakaria, 2019 [20] | Any primary malignancy except epithelial, basal, and squamous skin cancer | 7460 | Death-linked Canadian Cancer Registry | Among the 15–19 age group, 135 SMNs were observed. Compared to the general population, AYA cancer survivors were 4.3 times as likely (SIR) to experience an SMN (95% CI 3.6–5.1), corresponding with an AER of 15.9 per 10,000 person-years (95% CI 12.1–19.8). |
| Reulen, 2020 [27] | Any primary malignancy except myelodysplastic syndrome, Langerhans cell histiocytosis, chronic myeloproliferative or lymphoproliferative disorder, or an immunoproliferative disease | 21,402 | Linkage with population-based national cancer registries, follow-up clinics, questionnaires, available medical records, linkage with national mortality registries and linkage with health insurance registries | Among those diagnosed at age 15–19 years of age, the risk of SPN was: for any digestive (SIR:2.5, 95% CI: 2.1–2.9; AER: 26, 95% CI: 20–34); for colorectal (SIR:1.9, 95% CI: 1.5–2.5; AER: 9, 95% CI: 6–15); for colon only (SIR:2.0, 95% CI: 1.5–2.8; AER:6, 95% CI: 3–11); and for rectum only (SIR:1.8, 95% CI: 1.2–2.6; AER: 3, 95% CI: 1–8); liver (SIR:5.7, 95%, 95% CI: 3.6–8.9; AER: 5, 95% CI: 3–8); stomach (SIR:3.3, 95%, 95% CI: 2.2–4.8; AER: 6, 95% CI: 3–10); and pancreas (SIR:2.3, 95%, 95% CI: 1.4–3.8; AER: 3, 95% CI: 1–6) |
| Hodgkin lymphoma cohort | ||||
| Swerdlow, 2011 [28] | HL | 2291 | Medical databases, cancer registry information, clinical contact | SMNs developed in 459 of 5798 cohort members. |
| Swerdlow, 2012 [29] | First Primary: HL. SPN: Breast Cancer | 4767 | Review of medical records, by responses to questionnaires sent to general practitioners and record linkage with the Netherlands Cancer Registry | Breast cancer or ducta carcinoma in situ developed in 347 AYA cancer survivors. SIR and AERs per 10,000 person-years were elevated in all 5-year age groups. |
| Schaapveld, 2015 [30] | HL | 2736 | Case notes, cancer registries, reports from clinicians, screening clinics, and patient reports | For individuals who were aged 15–24 at the time of treatment for first HL, the SIR for experiencing any type of SMN was 8.4 (95% CI 7.5–9.5), with an associated AER of 111 per 10,000 person-years, compared to the general population. For individuals who were aged 25–34 at the time of treatment for first HL, the SIR for experiencing SMN was 5.0 (95% CI 4.4–5.6), with an associated AER of 118 per 10,000 person-years. |
| Xavier, 2015 [31] | HL | 5156 | SEER | SMN developed in 122 of 5156 people. At 150 months, the cumulative risk of SMN was 3.3% and 3.0% for people who had and had not received radiation therapy, respectively. |
| Bhuller, 2016 [32] | First Primary: HL. SPN: All cancers | 442 | British Columbia Cancer Registry | SIR for developing any SMN: 7.8 (95% CI 5.57–10.52); AER: 5.07 per 1000 person-years. Forty-one survivors (9%) developed SMN; 61% of whom were female. The most frequently developed SMN was breast cancer (n = 14). The risk of developing breast, lung, and thyroid cancer increased the most among cancer survivors. |
| van Eggermond, 2017 [33] | First primary malignancy: HL. SMN: colorectal cancer | 1009 | Cohort linkage with a nationwide network and registry of histo- and cytopathology and the Netherlands Cancer Registry | Sixteen cases of colorectal cancer were observed. HL survivors aged 25–34 had an increased risk of developing colorectal cancer compared to the general population (SIR:2.3, 95% CI 1.3–3.7; AER:4.9, 95% CI 1.2–10.3) |
| Other tumor-specific cohorts | ||||
| Goldfarb, 2014 [34] | Thyroid cancer | 41,062 | National Cancer Database | Among 41,062 cases of thyroid cancer, 1349 (3.3%) had experienced a prior malignancy. |
| Lee, 2014 [35] | First Primary: osteosarcoma. SMN: all cancers except osteosarcoma | 609 | SEER | 89 participants developed SMN, of whom 16.9% were aged 21–30. |
| Sultan, 2019 [36] | First primary malignancy: Ewing sarcoma. SMN: All cancers excluding in situ tumors | 324 | SEER | Of 1131 participants total, 324 were between 20–39 years of age. Of the 324, 9 developed SMN, of whom 8 were aged 20–29 and 1 was aged 30–39. |
| Abrahao, 2020 [37] | NHL | 4392 HIV-uninfected and 425 HIV-infected | California Cancer Registry | Ten-year cumulative incidence of second primary malignancy among HIV-uninfected patients (2·6%, 95% CI 2.0–3.1%) was lower compared to HIV-infected patients (8·1%, 95% CI 5.4–11.4%). |
| Gingrich, 2020 [38] | Cutaneous melanoma | 8259 | California Cancer Registry | At 10 years post-diagnosis, 6.4% AYAs developed subsequent cancers. The most common SPN were: melanoma (56.4%), breast (11.8%), thyroid (6.7%), and prostate (2.3%). |
| Muffly, 2020 [39] | ALL | 1069 | California Cancer Registry | The 5- and 10-year cumulative incidence of second cancer was 0.4 (95% CI 0.1–1.0) and 1.4 (95% CI 0.7–2.4), respectively. |
Abbreviations: AER, absolute excess risk; ALL, acute lymphoblastic leukemia; AYA, adolescent and young adult; CI, confidence interval; CNS, central nervous system; HL, Hodgkin lymphoma; HR, hazard ratio; NHL, non-Hodgkin lymphoma; SEER, National Cancer Institute’s Surveillance, Epidemiology and End Results Program; SIR, standardized incidence ratio; SMN, subsequent malignant neoplasm; SPN, second primary neoplasm.