Late effects of cancer at a young age: Registry-based studies of the health of cancer patients and their off-spring

Modern cancer therapy has resulted in increased survival among patients diagnosed with cancer at a young age. These improvements have led to the investigation of late morbidity and mortality associated with cancer and its treatments. The aim of this study was to evaluate late effects of cancer treated at a young age on the health of patients and their offspring. Utilising the nationwide population-based registries in Finland, we evaluated the risk of hypothyroidism and the probability of parenthood in cancer survivors as well as preterm birth, neonatal outcomes, and the risk of cancer among offspring of patients. The survivor cohort, identified from the Finnish Cancer Registry, consisted of 25,784 cancer patients diag-nosed between ages 0 and 34 in 1953–2004. By linkage to the population register, siblings of these patients were identified for comparison. The prevalence of hypothyroidism was higher among former childhood cancer (aged 0–16) patients than in the general population. The probability of parenthood following early onset cancer was overall significantly reduced compared to siblings. Offspring of female cancer survivors were at an increased risk of preterm birth, this risk being highest among patients diagnosed in childhood and early adulthood (aged 20–34 years). The offspring were not, however, at a significantly increased risk of neonatal death or stillbirth, though they were more likely to need monitoring or intensive care in the neonatal period. The risk of sporadic cancer among offspring of male and female cancer survivors was not elevated in comparison to the general population. The study showed that former cancer patients are at risk of certain adverse endocrine and reproductive health outcomes and should be followed for timely intervention. The offspring of cancer survivors do not appear to be at risk for adverse health outcomes.Siirretty Doriast

Lapsuusiän syöpää sairastaneiden naisten lisääntymisterveys

Vertaisarvioitu.Viime vuosikymmenien aikana tapahtuneen kehityksen myötä yli 80 % lapsena syövän sairastaneista on elossa viiden vuoden kuluttua syövän toteamisesta. Syöpähoidot saattavat kuitenkin vaurioittaa tytön munasarjoja pysyvästi. Tutkimusten mukaan lapsuusiän syövästä toipuneet saavatkin lapsia harvemmin kuin terveet väestöverrokit. Vaikka taustalla on usein tahaton lapsettomuus, myös tiedonpuute hoitojen riskeistä ja vaikutuksesta hedelmällisyyteen, seksuaalisuuteen ja raskauksiin voi olla osatekijä. Asiantunteva neuvonta syöpähoitojen vaikutuksesta lisääntymisterveyteen on ensiarvoisen tärkeää. Lapsuusiän syövästä toipuneiden naisten koeputkihedelmöityshoitojen määrä on viime vuosina selvästi lisääntynyt. Jos hoidot johtavat raskauteen, siihen liittyvät riskit ovat yleensä pieniä, ja lapsuudessa syöpää sairastaneet naiset voivat yleensä synnyttää lapsensa turvallisesti. .Peer reviewe

Completeness of Pediatric Cancer Registration in the Finnish Cancer Registry

Johdanto Suomen Syöpärekisteri ylläpitää rekisteriä kaikista Suomessa todetuista syöpätapauksista. Väestöpohjainen syöpätapausten rekisteröinti tarjoaa kattavan ja luotettavan tietokannan syöpätutkimuksessa käytettäväksi. Rekisteröinnin kattavuuden ja rekisteröidyn tiedon oikeellisuuden puutteilla voi kuitenkin olla suuri vaikutus erityisesti harvinaisten sairauksien insidenssi- prevalenssi- ja elossaoloarvioihin. Tutkimuksessamme pyrimme tarkentamaan aiempaa arviota lapsuussyövän rekisteröinnin kattavuudesta Suomen Syöpärekisterissä (Leinonen ym. 2017). Materiaalit ja menetelmät Poimimme Syöpärekisteristä sekä Hoitoilmoitusrekisteristä kaikki 0–14-vuotiaiden syöpätapaukset vuosina 2009–2013. Tarkastimme jokaisen Syöpärekisteristä puuttuneen tapauksen syöpädiagnoosin oikeellisuuden joko lähettämällä potilasta hoitaneeseen sairaalaan täytettävä lomake tai tarkastamalla potilastiedot potilastietoarkistoista. Laskimme Syöpärekisterin rekisteröinnin kattavuusarviot 95 %:n luottamusvälein tauti- sekä ikäryhmittäin. Tulokset Vuosina 2009–2013 Syöpärekisteriin oli rekisteröity 741 uutta lapsisyöpätapausta. Hoitoilmoitusrekisteriin syöpätapauksia oli rekisteröity 1072. Virheellisten syöpädiagnoosien karsimisen jälkeen vahvistimme 49:n syöpätapauksen puuttuvan Syöpärekisteristä. Syöpärekisterin kattavuudeksi arvioimme 94% (95% luottamusväli 91.9¬–95.4); 92% (95% luottamusväli 89.1–94.2) kiinteiden ja 97% (95% luottamusväli 94.1–98.4) ei-kiinteiden kasvainten osalta. Retinoblastooman rekisteröinnin kattavuus oli huomattavan matala, 54% (95% luottamusväli 36.4–71.9). Myös luusto- ja keskushermostosyöpien kattavuusarviot olivat matalat. Lymfoomien ja munuaissyöpien rekisteröinnin kattavuusarvio sen sijaan oli 100%. Diskussio Suomen Syöpärekisteri tuottaa korkealaatuista tietoa lapsuusajan syövistä. Ei-kiinteiden syöpien rekisteröinti on kattavampaa kuin kiinteiden syöpien. Syöpäilmoituksia Syöpärekisterille on puuttunut erityisesti potilaista, joiden tautia ei aina varmenneta histologisesti, kuten silmä- ja keskushermostosyöpäpotilaista

Maternal Thyroid Disease and the Risk of Childhood Cancer in the Offspring

Maternal thyroid disease, especially hypothyroidism, affects pregnancy and its outcome. In-utero exposure to autoimmune thyroid disease has been reported to associate with childhood ALL in the offspring. We evaluated the risk of childhood cancer in the offspring following exposure to maternal thyroid disease in a case-control setting using registry data. All patients with their first cancer diagnosis below the age of 20 years were identified from the Finnish Cancer Registry (n = 2037) and matched for sex and birth year at a 1:5 ratio to population controls identified from the Medical Birth Registry (n = 10,185). We collected national information on maternal thyroid disease from the Medical Birth Registry, Care Register for Health Care, Register for Reimbursed Drug Purchases and Register of Special Reimbursements. We used conditional logistic regression to analyze childhood cancer risk in the offspring. The adjusted OR for any childhood cancer was 1.41 (95%, CI 1.00–2.00) comparing the offspring of mothers with hypothyroidism and those with normal thyroid function. The risk of lymphomas was increased (adjusted OR for maternal hypothyroidism 3.66, 95%, CI 1.29–10.38). The results remained stable when mothers with cancer history were excluded from the analyses. Maternal hypothyroidism appears to be associated with an increased risk for childhood lymphoma in the offspring. The association exists even after excluding possible familial cancers

Maternal Thyroid Disease and the Risk of Childhood Cancer in the Offspring

Maternal thyroid disease, especially hypothyroidism, affects pregnancy and its outcome. In-utero exposure to autoimmune thyroid disease has been reported to associate with childhood ALL in the offspring. We evaluated the risk of childhood cancer in the offspring following exposure to maternal thyroid disease in a case-control setting using registry data. All patients with their first cancer diagnosis below the age of 20 years were identified from the Finnish Cancer Registry (n = 2037) and matched for sex and birth year at a 1:5 ratio to population controls identified from the Medical Birth Registry (n = 10,185). We collected national information on maternal thyroid disease from the Medical Birth Registry, Care Register for Health Care, Register for Reimbursed Drug Purchases and Register of Special Reimbursements. We used conditional logistic regression to analyze childhood cancer risk in the offspring. The adjusted OR for any childhood cancer was 1.41 (95%, CI 1.00–2.00) comparing the offspring of mothers with hypothyroidism and those with normal thyroid function. The risk of lymphomas was increased (adjusted OR for maternal hypothyroidism 3.66, 95%, CI 1.29–10.38). The results remained stable when mothers with cancer history were excluded from the analyses. Maternal hypothyroidism appears to be associated with an increased risk for childhood lymphoma in the offspring. The association exists even after excluding possible familial cancers

Preterm birth, neonatal therapies and the risk of childhood cancer

Our aim was to study the impact of preterm birth and neonatal therapies on the risk of childhood cancer using a nationwide, registry-based, case-control design. Combining population-based data from Finnish Medical Birth Registry (MBR) and Finnish Cancer Registry, we identified a total of 2029 patients diagnosed with cancer under the age of 20 years and 10 103 age- and sex-matched controls over the years 1996 to 2014. Information on the prenatal and perinatal conditions was obtained from the MBR. Gestational age was categorized into early (= 37 weeks). Cancer risk among the preterm compared to term neonates was evaluated using conditional logistic regression. We identified 141 cancers among the preterm (20.8% of 678) vs 1888 cancers in the term children (16.5% of 11 454). The risk of any cancer was increased for the preterm (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.06-1.57), especially for the early preterm (OR 1.84, 95% CI 1.16-2.92). The risk of acute myeloid leukemia (AML; OR 2.33, 95% CI 1.25-4.37), retinoblastoma (OR 3.21, 95% CI 1.22-8.41) and germ cell tumors (OR 5.89, 95% CI 2.29-15.18) was increased among the preterm compared to term. Germ cell tumors were diagnosed at a significantly younger age among the preterm. Neonatal therapies, for example, mechanical ventilation, were associated with an increased risk of childhood cancer independent of gestational age. Preterm, especially early preterm birth, is associated with an increased risk of childhood cancer, especially germ cell tumors and AML. Respiratory distress requiring neonatal intervention also appears to be associated with an increased risk.Peer reviewe

Risk factors for preterm delivery among early onset cancer survivors: A Finnish register-based study

Previous studies have shown an elevated risk for preterm delivery among early onset cancer survivors. Whether the preterm delivery starts spontaneously, due to possible uterine damage because of cancer treatment, or is induced due to maternal conditions is unclear. Our aim was to assess pregnancy related conditions in female cancer survivors possibly underlying the elevated risk for preterm labor. Nationwide cancer and birth registries were merged to identify 1,753 first deliveries of cancer survivors (diagnosed below 40 years of age) and 5,123 first deliveries of matched female comparison subjects between January 1991 and December 2013. Conditional logistic regression models were used to estimate the risk for pregnancy related conditions adjusting for maternal age, gestational age and smoking. We found an overall increased risk for hospitalization during pregnancy (OR 1.45, 95% CI 1.25-1.68), intrahepatic cholestasis (OR 2.86, 95% CI 1.09-7.49), fear of childbirth (OR 2.25, 95% CI 1.31-3.85) and mental disorders and diseases of the nervous system complicating pregnancy and labor (OR 5.89, 95% CI 2.31-15.00). Among survivors, 129 (7.4%) delivered preterm compared to 268 (5.2%) comparisons subjects (p = 0.004). We found a statistically significant increased risk for preterm delivery among cancer survivors with vaginal bleeding (OR 1.35, 95% CI 1.07-1.71) and pre-eclampsia (1.35, 95% CI 1.06-1.72) compared to comparison subjects with the same condition. Health professionals treating these women should be aware of these risks. In general, however, our results are reassuring when it comes to pregnancies among cancer survivors.Peer reviewe

Maternal autoimmune disease is not associated with cancer in the offspring

Aim Autoimmune disease and its medication are associated with increased cancer risk in adults, but it is unknown whether maternal autoimmune disease and/or medication use in pregnancy are associated with increased cancer risk in offspring. Methods In this case-control study, we identified all patients under 20 years of age with their first cancer diagnosis in 1996-2014 from the Finnish Cancer Registry (n = 2029) and 1:5 population-based controls (n = 10,103) from the Medical Birth Register. We obtained information on maternal autoimmune disease and its medication from the relevant Finnish registries and used conditional logistic regression to analyse the risk of offspring cancer after maternal autoimmune disease exposure. Results The odds ratio (OR) for cancer in offspring following maternal autoimmune exposure was 0.76 (95% confidence interval [CI] 0.47-1.23). Individual ORs for inflammatory bowel and connective tissue diseases were 1.08 (95% CI 0.56-2.01) and 0.50 (95% CI 0.23-1.08), respectively. The OR for maternal autoimmune medication was 0.95 (95% CI 0.80-1.14) overall and similar by drug subtype. There was an increased risk with medication in late pregnancy but the ORs were unstable owing to small numbers. Conclusion Our study does not support an increased cancer risk among offspring of women with autoimmune disease or its medication during pregnancy.Peer reviewe