Risk of subsequent primary lymphoma in a cohort of 69,460 five-year survivors of childhood and adolescent cancer in Europe: The PanCareSurFup study.

BACKGROUND Survivors of Hodgkin lymphoma (HL) are at risk of developing non-Hodgkin lymphoma (NHL) after treatment; however, the risks of developing subsequent primary lymphomas (SPLs), including HL and NHL, after different types of childhood cancer are unknown. The authors quantified the risk of SPLs using the largest cohort of childhood cancer survivors worldwide. METHODS The Pan-European Network for Care of Survivors After Childhood and Adolescent Cancer (PanCare) Survivor Care and Follow-Up Studies (PanCareSurFup) cohort includes 69,460 five-year survivors of childhood cancer, diagnosed during 1940 through 2008, from 12 European countries. Risks of SPLs were quantified by standardized incidence ratios (SIRs) and relative risks (RRs) using multivariable Poisson regression. RESULTS Overall, 140 SPLs, including 104 NHLs and 36 HLs, were identified. Survivors were at 60% increased risk of an SPL compared with the general population (SIR, 1.6; 95% confidence interval [CI], 1.4-1.9). Survivors were twice as likely to develop NHL (SIR, 2.3; 95% CI, 1.9-2.8), with the greatest risks among survivors of HL (SIR, 7.1; 95% CI, 5.1-10.0), Wilms tumor (SIR, 3.1; 95% CI, 1.7-5.7), leukemia (SIR, 2.8; 95% CI, 1.8-4.4), and bone sarcoma (SIR, 2.7; 95% CI, 1.4-5.4). Treatment with chemotherapy for any cancer doubled the RR of NHL (RR, 2.1; 95% CI, 1.2-3.9), but treatment with radiotherapy did not (RR, 1.2; 95% CI, 0.7-2.0). Survivors were at similar risk of developing a subsequent HL as the general population (SIR, 1.1; 95% CI, 0.8-1.5). CONCLUSIONS In addition to HL, the authors show here for the first time that survivors of Wilms tumor, leukemia, and bone sarcoma are at risk of NHL. Survivors and health care professionals should be aware of the risk of NHL in these survivors and in any survivors treated with chemotherapy

Risk of subsequent gliomas and meningiomas among 69,460 5-year survivors of childhood and adolescent cancer in Europe:the PanCareSurFup study

BACKGROUND: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort.METHODS: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940-2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated.RESULTS: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50.DISCUSSION: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms.</p

Trends in treatment of childhood cancer and subsequent malignant neoplasm risk

Namen dela: Z raziskavo smo želeli oceniti stopnjo tveganja in vrsto sekundarnih malignih neoplazem (SMN) pri osebah, zdravljenih zaradi raka v otroštvu ter povezavo s spremembami v zdravljenju. Preiskovanci in metode dela: V populacijsko raziskavo smo vključili 3271 oseb, ki so bile zdravljene zaradi raka v otroštvu do vključno 18. leta starosti v Sloveniji med letoma 1961 in 2013. Standardizirana incidenčna stopnja (SIR), absolutno presežno tveganje (AER) in kumulativna incidenca so glavni statistični kazalci, s katerimi smo opisali rezultate raziskave. Rezultati: V povprečnem času opazovanja 23.2 let je 230 oseb razvilo 273 sekundarnih neoplazem (SN), od tega 183 SMN, 34 meningeom in 56 ne-melanomski rak kože. Ti bolniki so bili v 10.5% zdravljeni z radioterapijo, v 31% s kemoterapijo, v 26.9% s kombinacijo kemoterapije in radioterapije in v 16.1% z operacijo. Tveganje za SMN je bilo skoraj 3-krat večje kot v splošni populaciji (SIR 2.995%CI 2.5-3.3) in je ostalo 2-krat večje tudi po dopolnjenem 50. letu starosti (SIR 2.095%CI 1.3-3.1). Kumulativna incidenca SMN 30 let po diagnozi raka v otroštvu je nižja za bolnike zdravljene pred letom 1970 (Pheterogenost<0.001). Kumulativna incidenca SMN je 40 let po diagnozi raka v otroštvu najnižja za bolnike zdravljene le z operacijo. Kljub manjši obremenitvi z obsevanjem po letu 1995, ni razlike v kumulativni incidenci SMN 15 let po diagnozi raka v otroštvu med obema skupinama bolnikov (Pepe Morijev test, p=0.11). Po dopolnjenem 40. letu starosti 80% vseh presežnih primerov SMN predstavljajo karcinomi ščitnice, dojke, tumorji osrednjega živčevja, karcinomi sečil in spolovil ter dihal. Tveganje za sekundarno levkemijo (SL) je v naši raziskavi 6-krat večje kot v splošni populaciji. Tveganje za SL je izenačeno, ne glede na čas diagnoze otroškega raka. Dve tretjini bolnikov je zbolelo za SL v prvih petih letih po diagnozi raka v otroštvu. Zaključki: Tveganje za SMN je pri osebah, zdravljenih zaradi raka v otroštvu, primerljivo s tistim v drugih populacijskih raziskavah. Presežno tveganje je po dopolnjenem 40. letu manjše zaradi naraščanja števila malignih neoplazem v splošni populaciji in dejstva, da je bil znaten del bolnikov v tej skupini zdravljen le z operacijo ali manj intenzivno kemoterapijo in radioterapijo. Kljub manjšemu deležu obsevanih otrok po letu 1995, ni razlike v kumulativni incidenci SMN 15 let po diagnozi otroškega raka v primerjavi z obdobjem pred letom 1995. Z daljšim časom opazovanja in naraščajočo starostjo oseb v kohorti narašča delež bolnikov s sekundarnimi karcinomi. Tveganje za SL je večje kot v ostalih raziskavah, saj smo vključili vse primere SL in je izenačeno ne glede na čas diagnoze otroškega raka.Objective: The aim of the study was to investigate long-term risk and spectrum of subsequent neoplasm (SN) in childhood cancer survivors and to identify how trends in therapy influenced cumulative incidence of SN. Materials and methods: The population-based cohort comprises 3271 childhood cancer patients diagnosed in Slovenia aged ⡤ 18 years between 1st January 1961 and 31st December 2013 with a follow-up through 31st December 2018. Main outcome measures are standardized incidence ratios (SIRs), absolute excess risks (AERs), and cumulative incidence of SN. Results: After median follow-up time of 23.2 years, 230 patients experienced 273 SN, including 183 subsequent malignant neoplasm (SMN), 34 meningiomas and 56 nonmelanoma skin cancers. 10.5% patients received radiotherapy only, 31% chemotherapy only, 26.9% a combination of chemotherapy and radiotherapy and 16.1% surgery only. The overall risk for SMN was almost 3 times more than expected (SIR 2.995%CI 2.5-3.3), with survivors still at 2-fold increased risk after attained age 50 years. The observed cumulative incidence of SMN at 30-years after diagnosis was lower for those diagnosed in 1960s, compared with the 1970s and the 1980s (Pheterogeneity<0.001). The observed cumulative incidence of SMN at 40-years after diagnosis was significantly lower for those treated with surgery only compared to chemotherapy and/or radiotherapy (Pheterogeneity<0.001). Despite reduced use of radiotherapy over time, there was no difference in cumulative incidence of SMN 15 years after diagnosis of childhood cancer for patients treated before or after 1995 (Pepe Mori\u27s test, p = 0.11). After attained 40 years of age thyroid, genitourinary, breast, CNS and respiratory tumors were responsible for 80% of the total AER. Compared to general population, childhood cancer survivors had a 6-fold overall increased risk of secondary leukemia (SL). No difference in risk of SL was observed regarding time of diagnosis of childhood cancer. Two thirds of patients developed SL within first 5 years of childhood cancer diagnosis. Conclusions: Our study reports almost 3-fold increase in SMN among survivors of childhood cancer compared with general population. The SIRs reported by attained age are like other population-based studies. SIR is decreasing with attained age because of a fact that survivors treated long time ago received treatments with minimal carcinogenic potential. With longer follow up time proportion of patients diagnosed with subsequent carcinomas increases. Despite reduced use of radiotherapy after 1995 no difference in cumulative incidence of SMN 15 years after diagnosis of childhood cancer was observed. Risk for SL was greater in our cohort than in other published series due to inclusion of all cases of SL. Risk for SL was not different regardless of time of diagnosis of childhood cancer

Risk of subsequent primary lymphoma in a cohort of 69,460 five-year survivors of childhood and adolescent cancer in Europe: The PanCareSurFup study

Background: Survivors of Hodgkin lymphoma (HL) are at risk of developing non-Hodgkin lymphoma (NHL) after treatment; however, the risks of developing subsequent primary lymphomas (SPLs), including HL and NHL, after different types of childhood cancer are unknown. The authors quantified the risk of SPLs using the largest cohort of childhood cancer survivors worldwide. Methods: The Pan-European Network for Care of Survivors After Childhood and Adolescent Cancer (PanCare) Survivor Care and Follow-Up Studies (PanCareSurFup) cohort includes 69,460 five-year survivors of childhood cancer, diagnosed during 1940 through 2008, from 12 European countries. Risks of SPLs were quantified by standardized incidence ratios (SIRs) and relative risks (RRs) using multivariable Poisson regression. Results: Overall, 140 SPLs, including 104 NHLs and 36 HLs, were identified. Survivors were at 60% increased risk of an SPL compared with the general population (SIR, 1.6; 95% confidence interval [CI], 1.4–1.9). Survivors were twice as likely to develop NHL (SIR, 2.3; 95% CI, 1.9–2.8), with the greatest risks among survivors of HL (SIR, 7.1; 95% CI, 5.1–10.0), Wilms tumor (SIR, 3.1; 95% CI, 1.7–5.7), leukemia (SIR, 2.8; 95% CI, 1.8–4.4), and bone sarcoma (SIR, 2.7; 95% CI, 1.4–5.4). Treatment with chemotherapy for any cancer doubled the RR of NHL (RR, 2.1; 95% CI, 1.2–3.9), but treatment with radiotherapy did not (RR, 1.2; 95% CI, 0.7–2.0). Survivors were at similar risk of developing a subsequent HL as the general population (SIR, 1.1; 95% CI, 0.8–1.5). Conclusions: In addition to HL, the authors show here for the first time that survivors of Wilms tumor, leukemia, and bone sarcoma are at risk of NHL. Survivors and health care professionals should be aware of the risk of NHL in these survivors and in any survivors treated with chemotherapy

Risk of subsequent primary oral cancer in a cohort of 69,460 5-year survivors of childhood and adolescent cancer in Europe:the PanCareSurFup study

BACKGROUND Survivors of childhood cancer are at risk of subsequent primary malignant neoplasms (SPNs), but the risk for rarer types of SPNs, such as oral cancer, is uncertain. Previous studies included few oral SPNs, hence large-scale cohorts are required to identify groups at risks. METHODS The PanCareSurFup cohort includes 69,460 5-year survivors of childhood cancer across Europe. Risks of oral SPNs were defined by standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence. RESULTS One hundred and forty-five oral SPNs (64 salivary gland, 38 tongue, 20 pharynx, 2 lip, and 21 other) were ascertained among 143 survivors. Survivors were at 5-fold risk of an oral SPN (95% CI: 4.4-5.6). Survivors of leukaemia were at greatest risk (SIR = 19.2; 95% CI: 14.6-25.2) followed by bone sarcoma (SIR = 6.4, 95% CI: 3.7-11.0), Hodgkin lymphoma (SIR = 6.2, 95% CI: 3.9-9.9) and soft-tissue sarcoma (SIR = 5.0, 95% CI: 3.0-8.5). Survivors treated with radiotherapy were at 33-fold risk of salivary gland SPNs (95% CI: 25.3-44.5), particularly Hodgkin lymphoma (SIR = 66.2, 95% CI: 43.6-100.5) and leukaemia (SIR = 50.5, 95% CI: 36.1-70.7) survivors. Survivors treated with chemotherapy had a substantially increased risk of a tongue SPN (SIR = 15.9, 95% CI: 10.6-23.7). CONCLUSIONS Previous radiotherapy increases the risk of salivary gland SPNs considerably, while chemotherapy increases the risk of tongue SPNs substantially. Awareness of these risks among both health-care professionals and survivors could play a crucial role in detecting oral SPNs early