Sperm Quality in 1252 Adolescents and Young Adults (AYAs) Undergoing Fertility Preservation Due to Cancer or Nonmalignant Diseases.

Purpose: To investigate the quality of emergency-collected semen samples aimed at sperm cryopreservation provided by adolescents and young adults (AYAs) presenting with cancer or nonmalignant diseases. Methods: This is a prospective cohort study of postpubertal males referred for sperm cryopreservation who provided at least one semen sample for fertility preservation at the Reproductive Medicine Clinic of Karolinska University Hospital, Stockholm, Sweden, between January 2009 and January 2020. Sperm quality was assessed by total sperm count, concentration, and motility. Sperm quality by disease groups was compared with the reference population data of fertile men defined by the World Health Organization (WHO). Results: Among the 1252 patients who provided samples for cryopreservation, 1063 had cancer and 189 had nonmalignant diseases. The most common malignant indications included testicular cancers (n = 501) and Hodgkin lymphoma (n = 102). Among those with nonmalignant disease, 35% (n = 66) had testicular disease. Sperm quality was significantly lower in all groups of patients with cancer compared with the reference population. In total, azoospermia was found in 8% of the patients with cancer, in 9% of those with nonmalignant testicular disease, and in 3% of the remaining men with nonmalignant disease. Conclusion: Sperm quality in adult patients with cancer was significantly impaired compared with the WHO reference population standards for fertile men. For adolescent patients, standard reference values are lacking. AYAs wishing to preserve fertility should receive individualized counseling regarding sperm quality at the time of cryopreservation, and in selected cases, banking of additional samples should be recommended depending on the sperm quality parameters.

Obstetric and perinatal outcomes in women with previous breast cancer: a nationwide study of singleton births 1973-2017.

STUDY QUESTION: What are the obstetric and perinatal outcomes in births to breast cancer survivors compared to women without previous breast cancer? SUMMARY ANSWER: Women who conceived during the first 2 years following a breast cancer diagnosis had a higher risk for preterm birth, induced delivery, and cesarean section, while no increased risks were observed in births conceived later than 2 years after a breast cancer diagnosis. WHAT IS KNOWN ALREADY: A recent meta-analysis found higher risks of cesarean section, preterm birth, low birthweight, and small for gestational age in pregnancies among breast cancer survivors. Less is known about rarer outcomes such as pre-eclampsia or congenital malformations. STUDY DESIGN SIZE DURATION: We conducted a population-based matched cohort study including all breast cancer survivors who gave birth to singletons 1973-2017 in Sweden, identified through linkage between the Swedish Cancer Register, the Medical Birth Register, and the National Quality Register for Breast Cancer. PARTICIPANTS/MATERIALS SETTINGS METHODS: Each birth following breast cancer (n = 926) was matched by maternal age at delivery, parity, and calendar year at delivery to 100 births in a comparator cohort of women (n = 92 490). Conditional logistic and multinomial regression models estimated relative risks (RR) with 95% CI. Subgroup analyses by time since diagnosis and type of treatment were performed. MAIN RESULTS AND THE ROLE OF CHANCE: Previous breast cancer was associated with higher risks of induced delivery (RR; 1.3, 1.0-1.6), very preterm birth (RR; 1.8, 1.1-3.0), and planned preterm birth (RR; 1.6, 1.0-2.4). Women who conceived within 1 year after breast cancer diagnosis had higher risks of cesarean section (RR; 1.7, 1.0-2.7), very preterm birth (RR; 5.3, 1.9-14.8), and low birthweight (RR; 2.7, 1.4-5.2), while the risks of induced delivery (RR; 1.8, 1.1-2.9), moderately preterm birth (RR; 2.1, 1.2-3.7), and planned preterm birth (RR; 2.5, 1.1-5.7) were higher in women who conceived during the second year after diagnosis. Women who conceived later than 2 years after breast cancer diagnosis had similar obstetric risks to their comparators. LIMITATIONS REASONS FOR CAUTION: As information on the end date of treatment was unavailable, the time between the date of diagnosis and conception was used as a proxy, which does not fully capture the effect of time since end of treatment. In addition, treatments and clinical recommendations have changed over the long study period, which may impact childbearing patterns in breast cancer survivors. WIDER IMPLICATIONS OF THE FINDINGS: Risks of adverse obstetric outcomes in breast cancer survivors were confined to births conceived within 2 years of diagnosis. As family building holds significance for numerous young breast cancer patients, these findings are particularly important to inform both breast cancer survivors and clinicians about future reproductive outcomes. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Swedish Cancer Society (grant number 22-2044 Pj A.L.V.J.), Karolinska Institutet Foundations (grant number: 2022-01696 F.E.L., 2022-01559 A.L.V.J.), and the Swedish Research Council (grant number: 2021-01657 A.L.V.J.). K.A.R.-W. is supported by grants from the Swedish Cancer Society (20 0170 F) and the Radiumhemmets Research Foundations for clinical researchers 2020-2026. The authors declare that they have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

TNM stage in the Nordic Cancer Registries 2004-2016: Registration and availability.

BACKGROUND AND PURPOSE: Stage at cancer diagnosis is an important predictor of cancer survival. TNM stage is constructed for anatomic solid cancer diagnoses from tumor size (T), nodal spread (N) and distant metastasis (M) and categorized in groups 0-I, II, II and IV. TNM stage is imperative in cancer diagnosis, management and control, and of high value in cancer surveillance, for example, monitoring of stage distributions. This study yields an overview of TNM availability and trends in stage distribution in the Nordic countries for future use in monitoring and epidemiologic studies. MATERIAL AND METHODS: TNM information was acquired from the cancer registries in Denmark, Norway, Sweden, and Iceland during 2004-2016 for 26 cancer sites in the three former countries and four in Iceland. We studied availability, comparability, and distribution of TNM stage in three periods: 2004-2008, 2009-2013, and 2014-2016, applying a previously validated algorithm of 'N0M0 for NXMX'. For cancers of colon, rectum, lung, breast, and kidney, we examined TNM stage-specific 1-year relative survival to evaluate the quality in registration of TNM between countries. RESULTS: Denmark, Sweden, and Iceland exhibited available TNM stage proportions of 75-95% while proportions were lower in Norway. Proportions increased in Sweden over time but decreased in Denmark. One-year relative survival differed substantially more between TNM stages than between countries emphasizing that TNM stage is an important predictor for survival and that stage recording is performed similarly in the Nordic countries. INTERPRETATION: Assessment and registration of TNM stage is an imperative tool in evaluations of trends in cancer survival between the Nordic countries.

Trends in lung cancer survival in the Nordic countries 1990-2016: The NORDCAN survival studies.

OBJECTIVES: The aim of this study was to evaluate if the previously reported improvements in lung cancer survival were consistent across age at diagnosis and by lung cancer subtypes. MATERIALS AND METHODS: Data on lung cancers diagnosed between 1990 and 2016 in Denmark, Finland, Iceland, Norway and Sweden were obtained from the NORDCAN database. Flexible parametric models were used to estimate age-standardized and age-specific relative survival by sex, as well as reference-adjusted crude probabilities of death and life-years lost. Age-standardised survival was also estimated by the three major subtypes; adenocarcincoma, squamous cell and small-cell carcinoma. RESULTS: Both 1- and 5-year relative survival improved continuously in all countries. The pattern of improvement was similar across age groups and by subtype. The largest improvements in survival were seen in Denmark, while improvements were comparatively smaller in Finland. In the most recent period, age-standardised estimates of 5-year relative survival ranged from 13% to 26% and the 5-year crude probability of death due to lung cancer ranged from 73% to 85%. Across all Nordic countries, survival decreased with age, and was lower in men and for small-cell carcinoma. CONCLUSION: Lung cancer survival has improved substantially since 1990, in both women and men and across age. The improvements were seen in all major subtypes. However, lung cancer survival remains poor, with three out of four patients dying from their lung cancer within five years of diagnosis.

Have the recent advancements in cancer therapy and survival benefitted patients of all age groups across the Nordic countries? NORDCAN survival analyses 2002-2021.

BACKGROUND: Since the early 2000s, overall and site-specific cancer survival have improved substantially in the Nordic countries. We evaluated whether the improvements have been similar across countries, major cancer types, and age groups. MATERIAL AND METHODS: Using population-based data from the five Nordic cancer registries recorded in the NORDCAN database, we included a cohort of 1,525,854 men and 1,378,470 women diagnosed with cancer (except non-melanoma skin cancer) during 2002-2021, and followed for death until 2021. We estimated 5-year relative survival (RS) in 5-year calendar periods, and percentage points (pp) differences in 5-year RS from 2002-2006 until 2017-2021. Separate analyses were performed for eight cancer sites (i.e. colorectum, pancreas, lung, breast, cervix uteri, kidney, prostate, and melanoma of skin). RESULTS: Five-year RS improved across nearly all cancer sites in all countries (except Iceland), with absolute differences across age groups ranging from 1 to 21 pp (all cancer sites), 2 to 20 pp (colorectum), -1 to 36 pp (pancreas), 2 to 28 pp (lung), 0 to 9 pp (breast), -11 to 26 pp (cervix uteri), 2 to 44 pp (kidney), -2 to 23 pp (prostate) and -3 to 30 pp (skin melanoma). The oldest patients (80-89 years) exhibited lower survival across all countries and sites, although with varying improvements over time. INTERPRETATION: Nordic cancer patients have generally experienced substantial improvements in cancer survival during the last two decades, including major cancer sites and age groups. Although survival has improved over time, older patients remain at a lower cancer survival compared to younger patients.

Survival trends for patients diagnosed with cutaneous malignant melanoma in the Nordic countries 1990-2016: The NORDCAN survival studies.

BACKGROUND: The survival in patients diagnosed with cutaneous malignant melanoma (CMM) has improved in the Nordic countries in the last decades. It is of interest to know if these improvements are observed in all ages and for both women and men. METHODS: Patients diagnosed with CMM in the Nordic countries in 1990-2016 were identified in the NORDCAN database. Flexible parametric relative survival models were fitted, except for Iceland where a non-parametric Pohar-Perme approach was used. A range of survival metrics were estimated by sex, both age-standardised and age-specific. RESULTS: The 5-year relative survival improved in all countries, in both women and men and across age. While the improvement was more pronounced in men, women still had a higher survival at the end of the study period. The survival was generally high, with age-standardised estimates of 5-year relative survival towards the end of the study period ranging from 85% in Icelandic men to 95% in Danish women. The age-standardised and reference-adjusted 5-year crude probability of death due to CMM ranged from 5% in Danish and Swedish women to 13% in Icelandic men. CONCLUSION: Although survival following CMM was relatively high in the Nordic countries in 1990, continued improvements in survival were observed throughout the study period in both women and men and across age.

Childbirth rates in women with myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPN) are associated with inferior pregnancy outcome, however, little is known about fertility and childbearing potential in women with MPN. In this study we aimed to describe reproductive patterns, as well as to quantify risk of miscarriage and stillbirth. Women aged 15-44 years with an MPN diagnosis 1973-2018, were identified in Swedish health care registers, and age-matched 1:4 to population controls. We identified 1141 women with MPN and 4564 controls. Women with MPN had a lower rate of childbirth (hazard ratio [HR] with 95% confidence interval was 0.78 (0.68-0.90)). Subgroup analysis showed that the rate was not significantly reduced in essential thrombocythemia, HR 1.02 (0.86-1.22) while the HR was 0.50 (0.33-0.76) in PV and 0.45 (0.28-0.74) in PMF. The risk of miscarriage was not significantly increased before MPN diagnosis, the HR during follow-up after diagnosis was 1.25 (0.89-1.76). Women with MPN were more likely to have had a previous stillbirth. Women with MPN had fewer children at diagnosis, and fewer children in total. In conclusion, the childbirth rate was lower among women with MPN than controls, but not among women with essential thrombocythemia.

Gonadotropin Releasing Hormone agonist (GnRHa) during chemotherapy and post-cancer childbirths - a Nationwide population-based cohort study of 24,922 women diagnosed with cancer in Sweden.

Background: Worldwide, an increasing number of women with cancer are receiving Gonadotropin Releasing Hormone agonist (GnRHa) co-treatment during chemotherapy aiming at ovarian protection. There is divergence among guidelines, and some have recommended GnRHa co-treatment for women with breast cancer, however, the effect of GnRHa on future fertility is uncertain. Methods: In this population-based cohort study we included all women diagnosed with cancer at ages 15-45 between July 2005 and March 2017 in Sweden, identified in the Swedish Cancer Register. Exposure to GnRHa co-treatment was captured using the Prescribed Drug Register. Post-cancer childbirth, extracted from the Medical Birth Register, was the main outcome. Secondary outcomes included childbirths achieved through natural conception (NC), infertility diagnosis and cancer mortality. For each outcome, adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were estimated using delayed-entry Cox models, stratified by age and cancer site. Findings: Among 24,922 women diagnosed with cancer, 1.5% had GnRHa co-treatment. Breast cancer diagnoses were found in 80.2% of GnRHa exposed women and the GnRHa exposure was not associated with higher rates of childbirth (aHR 1.23, 95% CI 0.80-1.89), or NC childbirth (aHR 1.02, 95% CI 0.62-1.67), whereas the rate of infertility was significantly higher (aHR 2.42, 95% CI 1.44-4.08). In women with lymphoma and other cancers, GnRHa exposure was not associated with higher rates of childbirth, NC childbirth or infertility. GnRHa exposure was not associated with higher cancer mortality for any cancer type. Interpretation: We did not find evidence of improved or maintained fertility, estimated as childbirth rates post-cancer, in women who received GnRHa during cancer treatment. Funding: This study was financed by research grants from The Swedish Cancer Society (CAN 2017/704; 190249Pj, 200170F), The Swedish Research Council (Dnr 2019-00446), the Nordic Cancer Union NCU (Grant 2017), The Swedish Childhood Cancer Fund (KP2016-0031), Radiumhemmets Forskningsfonder (Dnr: 201313), Stockholm County Council (FoUI-953912) and Karolinska Institutet (Dnr 2020-01963).

Risk factors for the increasing incidence of pregnancy-associated cancer in Sweden - a population-based study.

INTRODUCTION: The incidence of cancer during pregnancy and within first year post-delivery, ie pregnancy-associated cancer (PAC), is increasing in many countries, but little is known about risk factors for these trends. This study quantified incidence of PAC by trimesters and post-delivery periods, and assessed the role of maternal age, parity, immigrant status, education, smoking and body mass index for the risk and incidence trends of PAC. MATERIAL AND METHODS: We used data from the national birth and cancer registers in Sweden during 1973-2017 to define a register-based cohort of women aged 15-44 years. Incidence rates of PAC during pregnancy and up to 1 year post-delivery were calculated per 100 000 deliveries per year. Poisson regression with multiple imputation estimated incidence rate ratios with 95% confidence intervals adjusted by year, age, previous parity, immigrant status, education, smoking and BMI during 1990-2017, when information on risk factors was available. RESULTS: Among 4 557 284 deliveries, a total of 1274 (during pregnancy) and 3355 (within 1 year post-delivery) cases of PAC were diagnosed, with around 50 cases/year diagnosed during pregnancy and 110 cases/year during the first year post-delivery in the latest period 2015-2017. The most common cancer types during pregnancy were malignant melanoma, breast and cervical cancer, together accounting for 57% of cases during pregnancy and 53% during the first year post-delivery. The numbers of PAC were lower during pregnancy than during post-delivery for all tumor types with lowest numbers during first trimester. The PAC incidence rates increased over calendar time. High maternal age at diagnosis, smoking, nulliparity and non-immigrant background were associated with significantly higher risks of PAC. The increasing PAC incidence was in part explained by higher maternal age over time, but not by the other factors. CONCLUSIONS: High maternal age is the strongest risk factor for PAC. We show for the first time that smoking, nulliparity and non-immigrant background are also contributing risk factors for PAC. However, only high maternal age contributed significantly to the increasing incidence. Further studies on other potential risk factors for PAC are warranted, since our results indicate that age on its own does not fully explain the increase.

Risk of obstetric and perinatal complications in women presenting with breast cancer during pregnancy and the first year postpartum in Sweden 1973-2017: A population-based matched study.

INTRODUCTION: For women presenting with breast cancer during pregnancy, treatment guidelines were historically restricted to only surgical treatment. Over the past decades, chemotherapy administered during pregnancy has been gradually introduced. Although breast cancer treatments during ongoing pregnancy have been deemed safe, detailed information on potential obstetric risks is lacking. We aimed to assess the risk of adverse obstetric and perinatal outcomes of breast cancer in pregnancy and within 1 year postpartum and in relation to trimester at breast cancer diagnosis, tumor stage, and cancer treatment during pregnancy. MATERIAL AND METHODS: Population-based matched study. Women diagnosed with breast cancer during pregnancy in 1973-2017 were identified in the Swedish Cancer Register and the Medical Birth Register, with additional information from the National Quality Register for Breast Cancer. Each birth with maternal breast cancer (n = 208 pregnant, n = 672 postpartum) was matched by age, calendar year, and birth order to 10 unexposed births from cancer-free women in the population (n = 2080 and n = 6720). Adjusted conditional logistic and multinomial regression models were used to estimate odds ratios and relative risk ratios, commonly denoted relative risks (RR) with 95% confidence intervals (CI), of adverse obstetric and perinatal outcomes. RESULTS: Breast cancer during pregnancy was associated with higher risks of preterm birth, both planned (RR 67.1, 95% CI 33.2-135.6) and spontaneous preterm birth (RR 3.8, 95% CI 2.0-7.5), and low birthweight (<2500 g: RR 7.5, 95% CI 4.9-11.3). The associated risks were higher if the breast cancer was diagnosed in the second trimester, and of similar magnitude irrespective of stage and treatment groups. There was a higher risk of low birthweight for gestational age (<25th centile) if breast cancer was diagnosed in the first trimester (RR 2.8, 95% CI 1.1-7.3). Risks of other pregnancy complications were similar to those of unexposed women, as were risks of neonatal mortality and malformations. Postpartum breast cancer was only associated with bleeding during pregnancy (RR 1.6, 95% CI 1.0-2.8). CONCLUSIONS: Preterm birth and related adverse outcomes were more common in women diagnosed with breast cancer during pregnancy. Reassuringly, breast cancer was not associated with other maternal pregnancy complications or adverse outcomes in children.

Association between cumulative psychosocial adversity in the family and ADHD and autism: a family-based cohort study.

Cumulative exposure to psychosocial adversity at an early age has been shown to be a risk factor for attention-deficit hyperactivity disorder (ADHD) and autism that often co-occur. However, it is not clear if this association reflects a causal effect or familial confounding. We aimed to assess whether cumulative psychosocial adversity in the family increases the risk for ADHD and autism in offspring while accounting for unmeasured familial confounding. We used a population-based cohort of 1,877,901 individuals born in Sweden between 1990 and 2009. Participants were followed from the age of 3 until 2013, with a median follow up time of 13.8 years. We created a cumulative index based on 7 psychosocial adversity factors. We used Cox regression to estimate the hazard ratios (HRs) relating neurodevelopmental conditions to cumulative psychosocial adversity. To address familial confounding, the analyses were repeated in groups of relatives of different kinship: siblings and half-siblings and cousins. A dose-response relationship was observed between cumulative exposure to psychosocial adversity and ADHD at a general population level (covariate adjusted HRs (aHRs) with 95% confidence intervals ranged from 1.55 [one adversity; 1.53-1.58] to 2.65 [ ≥ 4 adversities; 1.98-3.54]). No clear dose-response relation was seen for autism (aHRs ranged from 1.04 [.59-1.84] to 1.37 [1.30-1.45]). HRs of ADHD and autism decreased with increasing level of kinship in the analysis of relatives. Cumulative exposure to psychosocial adversity was associated with both ADHD and autism in the general population, these associations were partly explained by unmeasured familial confounding between relatives. This highlights the need for using family-based designs in studies of psychosocial adversity and ADHD and autism.

Trends and outcomes of fertility preservation for girls, adolescents and young adults with Turner syndrome: A prospective cohort study.

Background: In Scandinavian countries, programs for fertility preservation (FP) are offered free of charge at tertiary-care university hospitals to all patients facing infertility risks due to malignant diagnoses or benign conditions. In this prospective study we aimed to investigate trends and outcomes of FP indicated by a diagnosis of Turner syndrome. Methods: Prospective cohort study of patients with Turner karyotype receiving fertility preservation counselling at the Karolinska University Hospital between 1 January 1999 and 31 December 2021. Results: The cohort included 100 women and girls that received counselling, whereof 27% were prepubertal girls, 59% were adolescents and 14% of adult age. Before 2006 all patients were referred for fertility counselling at the time of Turner diagnosis. Based on updated guidelines, mainly patients who showed signs of puberty were referred after 2006. As a result, spontaneous menarche was more common in the later period. In total, 39% of the cohort had monosomal karyotype (45X), 20% had 45X/46XX or 45X/47XXX mosaicisms and 36% had an X-chromosomal structural anomaly. Ovarian tissue cryopreservation was planned for 73% of all patients, and oocyte cryopreservation following gonadotropin stimulation was planned for 10% of the patients. Follicles were present in 25% of all biopsies analyzed. Adolescents were more likely to have follicles present (30%) than prepubertal girls (16%) or adult women (17%). The ten patients that underwent gonadotropin stimulation for oocyte cryopreservation underwent a total of 15 cycles and eight patients successfully preserved oocytes. In total, 26% of the cohort has undergone fertility treatment or expressed further interest in fertility preservation. Six women have given birth using donated oocytes and three following spontaneous conception. Two women have undergone re-transplantation of cryopreserved ovarian tissue, without regaining ovarian function, and none of the women that have cryopreserved oocytes has returned to use them. Conclusion: Fertility counselling for girls with Turner syndrome should ideally be offered at onset of spontaneous puberty to improve the chances of fertility preservation. Since the girls and women in this cohort are still young, the return rate and utilization of the preserved tissue and oocytes is expected to increase with time. Clinical Trial Registration: ClinicalTrials.gov, identifier NTC04602962.

Influence of various assumptions for the individual TNM components on the TNM stage using Nordic cancer registry data.

BACKGROUND: The stage at diagnosis is one of the most important predictors for cancer survival. TNM stage is constructed from T (tumor size), N (nodal spread), and M (distant metastasis) components. In many notifications to cancer registries, TNM information is incomplete with unknown N and/or M. We aimed to evaluate the influence of various assumptions for recoding missing N (NX) and M (MX) as N0 and M0 on the proportion with available TNM stage, stage-distribution, and stage-specific relative survival. MATERIAL AND METHODS: We identified 140,201 patients diagnosed with incident cancer of the colon, rectum, lung, breast, or kidney during 2014-2016 in Denmark, Norway, Sweden, or Iceland. Information on TNM were obtained from cancer registry records used for an update of the Nordic cancer statistics database NORDCAN. Patients were followed for death or emigration through 2017. We calculated proportions of available TNM stage, stage distribution, and stage-specific relative survival under different approaches for each cancer site and country. RESULTS: Application of the assumptions yielded higher numbers of cases with available TNM stage for stages 0-I, II, and III. We observed only minor differences in stage-specific one-year relative survival when applying N0M0 for missing N and M, especially for high completeness of TNM registrations, whereas relative survival for remaining cases with missing TNM stage declined substantially. CONCLUSION: We found no major changes in stage-specific one-year relative survival applying N0M0 for NXMX. We conclude that complete TNM information is preferable to making assumptions, but it seems reasonable to consider assuming N0M0 for missing N and M in future studies based on the Nordic cancer registries. An automatic algorithm, though, is not recommended without considering potential area-specific reasons for frequent use of NX and MX. Clinicians should be urged to report complete TNM information to improve surveillance of the TNM stage.

Age-specific survival trends and life-years lost in women with breast cancer 1990-2016: the NORDCAN survival studies.

BACKGROUND: A recent overview of cancer survival trends 1990-2016 in the Nordic countries reported continued improvements in age-standardized breast cancer survival among women. The aim was to estimate age-specific survival trends over calendar time, including life-years lost, to evaluate if improvements have benefited patients across all ages in the Nordic countries. METHODS: Data on breast cancers diagnosed 1990-2016 in Denmark, Finland, Iceland, Norway, and Sweden were obtained from the NORDCAN database. Age-standardized and age-specific relative survival (RS) was estimated using flexible parametric models, as was reference-adjusted crude probabilities of death and life-years lost. RESULTS: Age-standardized period estimates of 5-year RS in women diagnosed with breast cancer ranged from 87% to 90% and 10-year RS from 74% to 85%. Ten-year RS increased with 15-18 percentage points from 1990 to 2016, except in Sweden (+9 percentage points) which had the highest survival in 1990. The largest improvements were observed in Denmark, where a previous survival disadvantage diminished. Most recent 5-year crude probabilities of cancer death ranged from 9% (Finland, Sweden) to 12% (Denmark, Iceland), and life-years lost from 3.3 years (Finland) to 4.6 years (Denmark). Although survival improvements were consistent across different ages, women aged ≥70 years had the lowest RS in all countries. Period estimates of 5-year RS were 94-95% in age 55 years and 84-89% in age 75 years, while 10-year RS were 88-91% in age 55 years and 69-84% in age 75 years. Women aged 40 years lost on average 11.0-13.8 years, while women lost 3.8-6.0 years if aged 55 and 1.9-3.5 years if aged 75 years. CONCLUSIONS: Survival for Nordic women with breast cancer improved from 1990 to 2016 in all age groups, albeit with larger country variation among older women where survival was also lower. Women over 70 years of age have not had the same survival improvement as women of younger age.

Pregnancy and childbirth outcomes in women with myeloproliferative neoplasms-a nationwide population-based study of 342 pregnancies in Sweden.

Pregnancy and childbirth in women with myeloproliferative neoplasms (MPN) are reported to be associated with maternal thrombosis, hemorrhage, and placental dysfunction. To assess the risks of adverse events in pregnancy in women with MPN, we performed a large population-based study using Swedish health care registers, and included all pregnancies that had reached gestational week 22 (prior to 2008, week 28) during the years 1973-2017 in women with MPN. Control pregnancies were matched 1:1 for age, calendar year, and parity. We identified 342 pregnancies in 229 women with MPN. Preterm birth was significantly increased in pregnancies in MPN, 14% compared to 4% of pregnancies in controls (p < 0.001). Correspondingly, low birth weight (<2500 g) was also significantly increased in MPN pregnancies (p = 0.042). Stillbirth was rare, with two events (0.6%) in MPN, none in controls. Maternal thrombotic complications occurred in three (1%) of the pregnancies in MPN patients, compared to none in controls. Pregnancy-related bleeding affected 14% of pregnancies in MPN and 9% in controls (p < 0.110). Cesarean section was significantly more common in pregnancies in MPN. Incidence was 12.2 per 100.000 pregnancies. In summary, preterm birth was an important complication in MPN pregnancies, while maternal complications were less common than previously reported.

Relapse Rates and Disease-Specific Mortality Following Procedures for Fertility Preservation at Time of Breast Cancer Diagnosis.

Importance: Breast cancer (BC) is the most common indication for fertility preservation (FP) in women of reproductive age. Procedures for FP often include hormonal stimulation, but current data are scarce regarding whether using hormonal stimulation for FP is associated with any deterioration in BC prognosis. Objective: To investigate the risk of disease-specific mortality and relapse in women who underwent FP with or without hormonal stimulation compared with women who did not at time of BC diagnosis. Design, Setting, and Participants: This Swedish nationwide prospective cohort study was conducted to assess the safety of hormonal and nonhormonal FP procedures indicated by BC in Sweden from January 1, 1994, through June 30, 2017. Women were identified from any of the regional FP programs located at Swedish university hospitals. A total of 425 women were found to have undergone FP, and 850 population comparators who had not undergone FP were sampled from regional BC registers and matched on age, calendar period of diagnosis, and region. Relapse-free survival was assessed in a subcohort of 241 women who underwent FP and 482 women who had not, with complete data. Nationwide demographic and health care registers provided data on outcome, disease- and treatment-related variables, and socioeconomic characteristics. Data analyses were performed between November 2021 and March 2022 and completed in June 2022. Main Outcomes and Measures: Relapse and disease-specific mortality after a diagnosis of BC. Results: The final study population included 1275 women (mean [SD] age, 32.9 [3.8] years) at the time of BC diagnosis. After stratification by the matching variables age, calendar period, and region, and adjustment for country of birth, education, parity at diagnosis, tumor size, number of lymph node metastases, and estrogen receptor status, disease-specific mortality was similar in women who underwent hormonal FP (adjusted hazard ratio [aHR], 0.59; 95% CI, 0.32-1.09), women who underwent nonhormonal FP (aHR, 0.51; 95% CI, 0.20-1.29), and women who were not exposed to FP (reference). In a subcohort with detailed data on relapse, adjusted rate of disease-specific mortality and relapse were also similar among the groups who underwent hormonal FP (aHR, 0.81; 95% CI, 0.49-1.37), underwent nonhormonal FP (aHR, 0.75; 95% CI, 0.35-1.62), and were not exposed to FP (reference). Conclusions and Relevance: In this cohort study, FP with or without hormonal stimulation was not associated with any increased risk of relapse or disease-specific mortality in women with BC. Results of this study provide much needed additional evidence on the safety of FP procedures in women with BC and may influence current health care practice to the benefit of young women with BC who wish to preserve their fertility.

Survival trends in patients diagnosed with colon and rectal cancer in the nordic countries 1990-2016: The NORDCAN survival studies.

BACKGROUND: Survival of patients with colon and rectal cancer has improved in all Nordic countries during the past decades. The aim of this study was to further assess survival trends in patients with colon and rectal cancer in the Nordic countries by age at diagnosis and to present additional survival measures. METHODS: Data on colon and rectal cancer cases diagnosed in the Nordic countries between 1990 and 2016 were obtained from the NORDCAN database. Relative survival was estimated using flexible parametric models. Both age-standardized and age-specific measures for women and men were estimated from the models, as well as reference-adjusted crude probabilities of death and life-years lost. RESULTS: The five-year age-standardized relative survival of colon and rectal cancer patients continued to improve for women and men in all Nordic countries, from around 50% in 1990 to about 70% at the end of the study period. In general, survival was similar across age and sex. The largest improvement was seen for Danish men and women with rectal cancer, from 41% to 69% and from 43% to 71%, respectively. The age-standardized and reference-adjusted five-year crude probability of death in colon cancer ranged from 30% to 36% across countries, and for rectal cancer from 20% to 33%. The average number of age-standardized and reference-adjusted life-years lost ranged between six and nine years. CONCLUSION: There were substantial improvements in colon and rectal cancer survival in all Nordic countries 1990-2016. Of special note is that the previously observed survival disadvantage in Denmark is no longer present.

Cancer survival in women diagnosed with pregnancy-associated cancer: An overview using nationwide registry data in Sweden 1970-2018.

BACKGROUND: Pregnancy-associated cancer (PAC) is increasing over time in many countries. We provide a comprehensive, population-based overview of cancer survival in women with PAC across five decades. METHODS: We performed a nationwide cohort study of 121,382 women diagnosed with cancer at age 15-49 between 1970 and 2018 using birth and cancer registers in Sweden. Pregnancy-associated cancer was defined as diagnosed during pregnancy and within one year of delivery, while non-PAC was outside this window. Cox regression estimated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) comparing cancer mortality for PAC versus non-PAC. RESULTS: In total, 5079 women had a diagnosis of PAC. Cutaneous malignant melanoma, breast, cervical, thyroid and central nervous system (CNS) were the most common sites of PAC. A higher cancer mortality was observed in PAC versus non-PAC for breast (HR = 1.72, 95% CI 1.54-1.93) and uterine cancer (myometrium/unspecified) (8.62, 2.80-26.53), in which all PAC deaths were uterine sarcomas. Increased mortality was also observed in upper digestive tract cancer diagnosed during pregnancy and colon cancer diagnosed during first year after delivery. Contrary, the HR for CNS tumours was significantly decreased (0.71, 0.55-0.91). Survival after PAC improved for most sites over time, with survival after breast cancer during pregnancy in recent years being similar to that of non-pregnancy associated breast cancer. CONCLUSION: For the majority of sites, PAC was not associated with poorer prognosis compared to non-PAC, a finding which was stable over time. The main exceptions were breast cancer and rarer cancers, such as uterine sarcoma.

A Prospective Study on Fertility Preservation in Prepubertal and Adolescent Girls Undergoing Hematological Stem Cell Transplantation.

BACKGROUND: Hematological stem cell transplantation (HSCT) is an established method which has markedly increased the survival rate of hematologic malignancies since its introduction in the 1980's. The conditioning for HSCT has known gonadotoxic effects and often leads to premature loss of fertility. In this study we have prospectively followed a cohort of girls undergoing HSCT and studied the outcomes of fertility preservation treatments performed before or after HSCT, as well as the long-term reproductive outcome. METHODS: In this one-center prospective study, 39 girls counselled for fertility preservation prior to or after conditioning for HSCT for malignant or benign diseases at childhood or adolescence between 1990 and 2017 were included. The patients were presented with the option to undergo cryopreservation of ovarian tissue or oocytes depending on their age and the time available. Follicle counts of the ovarian tissue and number of oocytes collected before or after HSCT were compared between patients treated for benign and malignant diseases. Hormone measurements post HSCT treatment, including FSH and AMH, reproductive outcomes and overall survival until January 2021 were investigated. RESULTS: In total, 34 girls and adolescents underwent fertility preservation before or after HSCT. Before HSCT, ovarian tissue was cryopreserved in 15 patients and two patients had oocytes preserved. Thirteen patients cryopreserved ovarian tissue after HSCT and seven patients returned to cryopreserve oocytes. Follicles were present in all tissue samples collected prior to HSCT, and in more than half of the samples collected post-HSCT. Half of the patients had spontaneous menarche or resumed menstruation post HSCT. Overall, 35 patients had survived at end of follow up and 7 patients had achieved parenthood. CONCLUSIONS: Since fertility loss is common following HSCT, fertility preservation should be offered to all patients. Fertility preservation treatments can be performed both before and after HSCT. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/show/NCT04602962, identifier NTC04602962.