Childbirth rates in classical Hodgkin lymphoma (cHL) survivors have historically been reduced compared to the general population. Understanding if contemporary treatment protocols are associated with reduced fertility is crucial as treatment guidelines shift toward more liberal use of intensive chemotherapy. We identified 2834 individuals aged 18‐40 years with cHL in Swedish and Danish lymphoma registers, and in the clinical database at Oslo University Hospital diagnosed 1995‐2018, who were linked to national medical birth registers. Cox regression adjusted for stage, performance status, year, and age at diagnosis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) contrasting time to first childbirth by treatment groups (ABVD, 2‐4 BEACOPP, 6‐8 BEACOPP) up to 10 years after diagnosis. Overall, 74.8% of patients were treated with ABVD, 3.1% with 2‐4 BEACOPP and 11.2% with 6‐8 BEACOPP. Adjusted HRs comparing childbirth rates in individuals treated with 6‐8 BEACOPP, and 2‐4 BEACOPP to ABVD were 0.53 (CI: 0.36‐0.77) and 0.33 (CI: 0.12‐0.91) for males, and 0.91 (CI: 0.61‐1.34) and 0.38 (CI: 0.12‐1.21) for females. Cumulative incidence of childbirths after 10 years was 19.8% (CI: 14.5%‐27.0%) for males and 34.3% (CI: 25.8%‐45.6%) for females treated with 6‐8 BEACOPP. Proportions of children born after assisted reproductive technique (ART) treatments were 77.4% (CI: 60.2‐88.6%) for males following 6‐8 BEACOPP, and <11% for females. Among ABVD treated patients the corresponding proportions were 12.2% (CI: 8.5%‐17.3%) and 10.6% (CI: 7.4%‐14.9%). BEACOPP treatment is associated with decreased childbirth rates compared to ABVD in male, but not female, cHL patients, despite widespread access to ART in the Nordics.

ObjectivesTo facilitate high-quality register-based research on colorectal cancer (CRC) in Sweden by constructing a database consisting of CRC patients, matched comparators, and relatives.Material and methodsPatients with adenocarcinoma in the colon and/or rectum were identified in the Swedish Colorectal Cancer Register, a nationwide quality-of-care register. For each patient, six comparators from the general population were matched on birth year, sex, year of CRC diagnosis, and county. Comparators were free from CRC at the time of matching, but could later become cases. For both patients and comparators, first-degree relatives (parents, siblings, and children) were identified. Information from nationwide population-based registers was retrieved and linked to each individual in the database using the personal identification number unique to all Swedish residents.ResultsA total of 76,831 CRC patients diagnosed between 1995 and 2016 were identified (51% colon, 49% rectal; before 2007 only rectal cancer patients were included). Among all patients, 37% were stage I-II, 22% stage III, and 22% stage IV. The median follow-up time was 11.9 years (inter-quartile range, IQR: 8.6-15.3). Together with comparators and relatives, the database contains 2,413,139 individuals with information on demographics, dates and causes of death, in- and outpatient healthcare records, cancer diagnoses, prescribed and dispensed drugs, childbirths (among women), and social security information (such as sick leave and early retirement).ConclusionThe Colorectal Cancer Database Sweden (CRCBaSe) is a large and unique register-based data research platform, which opens up for clinically important, large epidemiological studies with innovative design in the field of colorectal adenocarcinoma.

In this population-based study, we aimed to characterize and compare subgroups of therapy-related Myelodysplastic syndromes (t-MDS) and define the implications of type of previous treatment and primary disease. We combined data from MDS patients, diagnosed between 2009 and 2017 (n = 2705), in the nationwide Swedish MDS register, with several health registers. Furthermore, using matched population controls, we investigated the prevalence of antecedent malignancies in MDS patients in comparison with the general population. This first ever nationwide study on t-MDS confirms a shorter median survival for t-MDS compared to de novo MDS (15.8 months vs 31.1 months, p < 0.001). T-MDS patients previously treated with radiation only had disease characteristics with a striking resemblance to de novo-MDS, in sharp contrast to patients treated with chemotherapy who had a significantly higher risk profile. IPSS-R and the WHO classification differentiated t-MDS into different risk groups. As compared with controls, MDS patients had a six-fold increased prevalence of a previous hematological malignancy but only a 34% increased prevalence of a previous solid tumor. T-MDS patients with a previous hematological malignancy had a dismal prognosis, due both to mortality related to their primary disease and to high-risk MDS.

Background: In mantle cell lymphoma (MCL), time to relapse is a critical factor, and patients experiencing disease progression within 24 months from treatment start (POD24) have inferior survival. However, the cut-off at 24 months is arbitrary and potentially overly simplified. We aimed to quantify the impact of the timing of disease progression on overall survival, stratified by the most common first-line treatment concepts (Nordic-MCL, R-Bendamustin, and R-CHOP). Methods: Using the population-based Swedish lymphoma register, we identified all systemically treated MCL patients diagnosed between 2006 and 2018. We supplemented this with information on progression and relapse from medical chart reviews through 2022. Patients were categorized based on first-line treatment (Nordic MCL regimen, R-Bendamustin, R-CHOP, and others). POD was defined as a lack of response to primary therapy (progressive disease [PD]) or an initial response followed by a relapse. To assess the impact of POD timing on survival, we used an illness-death model with transition rates estimated using flexible parametric survival models to predict the five-year overall survival (OS) conditional on either being progression-free or experiencing POD as a smooth function of time since primary treatment. Results: A total of 1193 patients receiving systemic treatment were included. The median age at diagnosis was 70 years, and patients were followed for a median of 4 years (range 0–16 years, alive patients, six years). 33% of patients received R-Bendamustin (n = 387, median age 75 years), 30% received the Nordic MCL regimen (n = 351, median age 62 years), and 23% received R-CHOP (n = 276, median age 72 years). Almost half of the patients (48%, n = 571) experienced POD during follow-up. The five-year OS from treatment start was 47%, and progression-free survival was 32%. Among patients treated in the first line with either R-Bendamustin or the Nordic MCL protocol, those with a POD had substantially lower 5-year OS compared to patients who remained progression-free, also for POD occurring up to six years after primary treatment. For patients treated with R-CHOP, the impact of POD was largest if it occurred within 2–3 years after first-line therapy. Keyword: Aggressive B-cell non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Incidence of early-onset (<50 years) colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. In a nationwide nested case–control study, we included all EOCRC cases in Sweden diagnosed during 2007–2016, together with controls, matched for birth year, sex, and county. Information on exposure of autoimmune or metabolic disease was collected from the National Patient Register and Prescribed Drugs Registry. Hazard ratios (HR) as measures of the association between EOCRC and the exposures were estimated using conditional logistic regression. In total, 2626 EOCRC patients and 15,756 controls were included. A history of metabolic disease nearly doubled the incidence hazard of EOCRC (HR 1.82, 95% CI 1.66–1.99). A sixfold increased incidence hazard of EOCRC (HR 5.98, 95% CI 4.78–7.48) was seen in those with inflammatory bowel disease (IBD), but the risk increment decreased in presence of concomitant metabolic disease (HR 3.65, 95% CI 2.57–5.19). Non-IBD autoimmune disease was not statistically significantly associated with EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines.

BACKGROUND:Colorectal anastomotic leakage is consistently more common in men, regardless of tumour location. This fact is largely unexplained but might be a consequence of biological differences including hormonal exposure and not only related to anatomy.METHODS:This was a retrospective, nationwide registry-based observational study of post-menopausal women operated for colorectal cancer with an anastomosis between 2007 and 2016. Hormonal exposure before surgery, as defined by prescribed drugs affecting oestrogen levels, was related to postoperative anastomotic leakage, using mixed-effects logistic regression models with adjustment for confounding. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were derived. In addition, separate estimates according to tumour location were computed, and a sensitivity analysis excluding topical oestrogen hormone exposure was conducted.RESULTS:Some 16,535 post-menopausal women were included, of which 16.2% were exposed to drugs increasing oestrogen levels before surgery. In this exposed group compared to the unexposed, leak rates were 3.1 and 3.8%, respectively. After adjustment, a reduction of anastomotic leakage in the exposed group was detected (OR: 0.77; 95% CI: 0.59-0.99). This finding was largely attributed to the rectal cancer subgroup (OR: 0.55; 95% CI: 0.36-0.85), while the exclusion of topical oestrogen drugs further reduced the estimates of the main analysis (OR: 0.63; 95% CI: 0.38-1.02).CONCLUSIONS:Anastomotic leakage rates are lower in women exposed to hormone replacement therapy before surgery for colorectal cancer, which might explain some of the difference in leak rates between men and women, especially regarding rectal cancer.

In follicular lymphoma (FL), progression of disease ≤24 months (POD24) has emerged as an important prognostic marker for overall survival (OS). We aimed to investigate survival more broadly by timing of progression and treatment in a national population-based setting. We identified 948 stage II-IV indolent FL patients in the Swedish Lymphoma Register diagnosed 2007–2014 who received first-line systemic therapy, followed through 2020. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by first POD at any time during follow-up using Cox regression. OS was predicted by POD using an illness-death model. During a median follow-up of 6.1 years (IQR: 3.5–8.4), 414 patients experienced POD (44%), of which 270 (65%) occurred ≤24 months. POD was represented by a transformation in 15% of cases. Compared to progression-free patients, POD increased all-cause mortality across treatments, but less so among patients treated with rituximab(R)-single (HR = 4.54, 95% CI: 2.76-7.47) than R-chemotherapy (HR = 8.17, 95% CI: 6.09-10.94). The effect of POD was similar following R-CHOP (HR = 8.97, 95% CI: 6.14-13.10) and BR (HR = 10.29, 95% CI: 5.60-18.91). The negative impact of POD on survival remained for progressions up to 5 years after R-chemotherapy, but was restricted to 2 years after R-single. After R-chemotherapy, the 5-year OS conditional on POD occurring at 12, 24, and 60 months was 34%, 46%, and 57% respectively, versus 78%, 82%, and 83% if progression-free. To conclude, POD before but also beyond 24 months is associated with worse survival, illustrating the need for individualized management for optimal care of FL patients.

Studies on late effects in patients with mantle cell lymphoma (MCL) are becoming increasingly important as survival is improving, and novel targeted drugs are being introduced. However, knowledge about late effects is limited. The aim of this population-based study was to describe the magnitude and panorama of late effects among patients treated with or without high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT). The study cohort included all patients with MCL, recorded in the Swedish Lymphoma Register, aged 18 to 69 years, diagnosed between 2000 and 2014 (N = 620; treated with HD-ASCT, n = 247) and 1:10 matched healthy comparators. Patients and comparators were followed up via the National Patient Register and Cause of Death Register, from 12 months after diagnosis or matching to December 2017. Incidence rate ratios of the numbers of outpatient visits, hospitalizations, and bed days were estimated using negative binomial regression models. In relation to the matched comparators, the rate of specialist and hospital visits was significantly higher among patients with MCL. Patients with MCL had especially high relative risks of infectious, respiratory, and blood disorders. Within this observation period, no difference in the rate of these complications, including secondary neoplasms, was observed between patients treated with and without HD-ASCT. Most of the patients died from their lymphoma and not from another cause or treatment complication. Taken together, our results imply that most of the posttreatment health care needs are related to the lymphoma disease itself, thus, indicating the need for more efficient treatment options.

Colorectal anastomotic leakage is consistently more common in men, regardless of tumour location. This fact is largely unexplained but might be a consequence of biological differences including hormonal exposure and not only related to anatomy. This was a retrospective, nationwide registry-based observational study of post-menopausal women operated for colorectal cancer with an anastomosis between 2007 and 2016. Hormonal exposure before surgery, as defined by prescribed drugs affecting oestrogen levels, was related to postoperative anastomotic leakage, using mixed-effects logistic regression models with adjustment for confounding. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were derived. In addition, separate estimates according to tumour location were computed, and a sensitivity analysis excluding topical oestrogen hormone exposure was conducted. Some 16,535 post-menopausal women were included, of which 16.2% were exposed to drugs increasing oestrogen levels before surgery. In this exposed group compared to the unexposed, leak rates were 3.1 and 3.8%, respectively. After adjustment, a reduction of anastomotic leakage in the exposed group was detected (OR: 0.77; 95% CI: 0.59–0.99). This finding was largely attributed to the rectal cancer subgroup (OR: 0.55; 95% CI: 0.36–0.85), while the exclusion of topical oestrogen drugs further reduced the estimates of the main analysis (OR: 0.63; 95% CI: 0.38–1.02). Anastomotic leakage rates are lower in women exposed to hormone replacement therapy before surgery for colorectal cancer, which might explain some of the difference in leak rates between men and women, especially regarding rectal cancer.

Introduction: Ability to discuss emotions can significantly strengthen the patient–Health Care Professional (HCP) relationship and improve outcomes. Communication barriers impede this relationship and limit the ability of HCPs to provide patient-centered care. Emojis are a universal language that has the potential to overcome these issues and are particularly suited for describing emotions. Aim: This 3-phase feasibility study aimed to collate current opinions around the utility of emojis in patient–HCP communication. Methods: In phase 1, a survey was conducted between September and October 2021 among members of the War On Cancer digital platform community (patients, friends, family, and others interested in the study) to determine how they used emojis in their personal and healthcare communications. In phase 2 (February 2022), selected patients were individually interviewed via zoom (9 questions; 30–60 minutes) to evaluate their current use of emojis in text-based communications, situations where emojis might and might not help them express themselves to HCPs, and emotions represented by different emojis. In phase 3 (February 2022), invited HCPs were individually interviewed face-to-face or via Zoom (6 open-ended questions; 30–45 minutes) to evaluate their current use of digital communications and emojis with patients, insights on the findings from phases 1 and 2, and overall thoughts on using emojis in patient communications. Results: The phase 1 survey had 290 respondents aged 15–84 years from 22 countries. The majority used emojis to express emotions in personal conversations and were positive about using them in HCP communications. In phase 2, 8 patients aged 30–70 years from the UK, US, and Sweden were interviewed. All used emojis in personal communications and a minority had used emojis to communicate with their HCP. Most interpreted emojis similarly, yet participants had varying views on when and how they should be used with HCPs, mainly because of the potential ambiguous interpretation. Some noted a lack of healthcare–adapted emojis. Participants identified 4 situations where emojis could be useful in HCP communication: emotional preparation before a visit, follow-up after a visit, situations with a language barrier, and to replace numeric scales for strength of emotion. Emojis were considered less useful as a substitute for face-to-face meetings, in serious situations, and when expressing serious emotions. In phase 3, 5 HCP volunteers (2 clinicians, 3 nurses) aged 30–45 years from the US and Sweden were interviewed. All communicated digitally with patients through electronic medical records or other platforms, sometimes only one-way (HCP to patient). No HCPs had used emojis directly with patients, noting that some platforms prohibit it. HCPs agreed with the scenarios identified in phase 2, further suggesting emojis may be most helpful for patients with poor literacy or who have difficulty expressing emotions. Conclusions: The findings of this survey and interviews demonstrated that both patients and HCPs recognize potential advantages in using emojis within healthcare conversations. Further research is required to determine the optimal settings in which emojis can be used to improve communications between patients and HCPs, and the associated clinical value.

Summary Previous studies concerning reproductive patterns among non‐Hodgkin lymphoma (NHL) survivors are scarce and those available have reported conflicting results. Treatment regimens vary considerably between aggressive and indolent NHL and studies of reproductive patterns by subtypes are warranted. In this matched cohort study, we identified all NHL patients aged 18–40 years and diagnosed between 2000 and 2018 from the Swedish and Danish lymphoma registers, and the clinical database at Oslo University Hospital ( n = 2090). Population comparators were matched on sex, birth year and country ( n = 19 427). Hazard ratios (HRs) were estimated using Cox regression. Males and females diagnosed with aggressive lymphoma subtypes had lower childbirth rates (HR female : 0.43, 95% CI: 0.31–0.59, HR male : 0.61, 95% CI: 0.47–0.78) than comparators during the first 3 years after diagnosis. For indolent lymphomas, childbirth rates were not significantly different from comparators (HR female : 0.71, 95% CI: 0.48–1.04, HR male : 0.94, 95% CI: 0.70–1.27) during the same period. Childbirth rates reached those of comparators for all subtypes after 3 years but the cumulative incidence of childbirths was decreased throughout the 10‐year follow‐up for aggressive NHL. Children of NHL patients were more likely to be born following assisted reproductive technology than those of comparators, except for male indolent lymphoma patients. In conclusion, fertility counselling is particularly important for patients with aggressive NHL.

The outcome for patients with mantle cell lymphoma (MCL) has drastically improved with new treatments directed toward the tumor immune microenvironment, where macrophages play an important role. In MCL, the presence of M2 macrophages defined by CD163 expression in diagnostic biopsies has been associated with a worse prognosis. An alternative way to assess the abundance of M2 macrophages is by measuring the level of soluble CD163 in serum (sCD163). We aimed to investigate the prognostic value of sCD163 in 131 patients with MCL. We found that high sCD163 at diagnosis was associated with shorter progression-free survival (PFS) and shorter overall survival (OS) in 81 patients who were newly diagnosed and subsequently treated with chemoimmunotherapy. The same was seen in a cohort of 50 patients with relapsed MCL that were mainly treated within the phase 2 Philemon-trial with rituximab, ibrutinib, and lenalidomide. In patients who were newly diagnosed and had low levels of sCD163, 5-year survival was 97%. There was a moderate correlation between sCD163 and tissue CD163. The association with a poor prognosis was independent of MCL international prognostic index, Ki67, p53 status, and blastoid morphology, as assessed in a multivariable Cox proportional hazards model. In this study, high sCD163 was associated with both shorter PFS and shorter OS, showing that high levels of the M2 macrophage marker sCD163 is an independent negative prognostic factor in MCL, both in the chemoimmunotherapy and ibrutinib/lenalidomide era. In addition, low sCD163 levels identify patients with MCL with a very good prognosis.

Introduction Diseases of the circulatory system (DCS) are some of the most common late effects of Hodgkin lymphoma (HL), primarily due to mediastinal radiotherapy and/or anthracycline-containing chemotherapy (e.g., ABVD and BEACOPP). As DCS is very common in the general population, modelling DCS attributable to HL therapy versus that expected in the general population is relevant to understand the magnitude of DCS reduction that could be achieved with less cardiotoxic therapies. This real-world data study used multi-state modelling and relative survival to estimate treatment-related DCS risk in HL survivors. Material and methods All HL patients registered in the Swedish Lymphoma Register 2000-2018, aged 18-80 years at diagnosis, and treated with anthracycline-containing therapy were included. DCS events were identified in the Swedish National Inpatient Register (ICD-10 codes I00-I99) and defined as the first admission for DCS after HL diagnosis. Sex-, year-, and age-specific DCS incidence rates in the general population were retrieved from public records. Patients were followed from treatment initiation through a series of states: alive and DCS-free, alive and with (excess or expected) DCS, dead without DCS, and dead after DCS. Follow-up ended on date of death, emigration, or December 31st, 2019, whichever came first. All state transitions were modelled separately using flexible parametric survival models, yielding hazard ratios (HR) with 95% confidence intervals (CI). A relative survival model incorporating the expected DCS rates was fitted to allow for estimation of excess DCS, which was then interpreted as treatment-related. Transition probabilities (i.e., the likelihood of being in a state) were predicted for specific patient groups, by sex and low/high (≤200/>200 mg/m2) cumulative anthracycline dose. Results In a total of 1,929 HL patients, the mean age at diagnosis was 42 years, 54% were males, and 49% were treated with high dose anthracycline (Table 1). The distribution of treatments was 66% ABVD, 20% CHOP-like, and 14% BEACOPP. During a median follow-up of 7.6 years (IQR: 4.5-11.0), 145 (7.5%) died without DCS, 377 patients (20%) were diagnosed with DCS, and 87 (5%) died after DCS. Figure 1a shows the sex-specific transition probabilities for a patient with advanced stage disease, diagnosed in 2000, at age 50, and treated with a cumulative anthracycline dose of >200mg/m2 in a ABVD regimen. The probability of being in the treatment-related (excess) DCS state at 10 years after first line treatment was 0.35 (95% CI: 0.09-0.75) for males and 0.41 (95% CI: 0.10-0.81) for females in this patient group. Figure 1b shows the probabilities for limited stage male patients diagnosed in 2000 at age 50, treated with ABVD, by low/high anthracycline dose. Here, the probability of being in the treatment-related (excess) DCS state at 10 years was 0.44 (95% CI: 0.16-0.76) and 0.53 (95% CI: 0.25-0.80) for low and high dose anthracycline patients, respectively. There were no significant differences in treatment-related (excess) DCS incidence rates or post DCS all-cause mortality rates (Table 1). Females had a significantly lower non-DCS mortality rate than males (adj. HR=0.69, 95% CI: 0.49-0.97), as did patients treated with high compared to low anthracycline dose (adj. HR=0.28, 95% CI: 0.18-0.44). Conclusion After 10 years, females had higher risks of treatment-related (excess) DCS compared to males, although not statistically significant and likely due to superior survival. The same was seen for high compared to low cumulative doses of anthracycline. Female sex and high dose anthracycline reduced the non-DCS mortality rate, but not the excess DCS incidence rate. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Purpose: Diagnostic laparotomy and splenectomy (DLS) were introduced for Hodgkin lymphoma (HL) patients in Sweden in the late 1960s/early-70s. It was soon established that splenectomised and functional hyposplenic (following irradiation) HL patients carried an increased risk of overwhelming infections, Streptococcus pneumoniae being the major causative agent. Despite this, DLS remained as a staging procedure for more than two decades. The purpose of this study was to compare incidence and outcome of pneumococcal infections between splenectomised (spl+) and non-splenectomised (spl-) HL patients. Material and Methods: HL patients diagnosed 1973–1995 were identified in the Swedish Cancer Register. Information on splenectomies and severe pneumococcal infections was retrieved from the National Inpatient Register. Follow-up started a diagnosis and ended on date of infection, emigration, death, or December 31, 2010, whichever came first. Splenectomy was analysed as a time-varying covariate, i.e., patients were considered unexposed before the date of splenectomy and exposed after the date of splenectomy. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) comparing infection rates between spl+/spl- patients. Results: A total of 4,237 HL patients were included, among whom 735 (17%) underwent a splenectomy, with a median time from splenectomy to infection of 6.8 years (range 0.1–30.8 years). The number of patients experiencing a severe pneumococcal infection was 39 (3.2 per 1,000 person-years) among spl+ and 60 (1.7 per 1,000 person-years) among spl- patients. The relative rate of severe pneumococcal infection comparing spl+/spl- HL patients was 2.43 (95% CI: 1.55–3.81), adjusted for diagnosis year, diagnosis age, and sex. The 30-day post-infection mortality proportion was 9/39 (23%) among the spl+ and 18% (11/60) among the spl- patients. Broken down by calendar period of infection, the 30-day post-infection mortality proportion among splenectomised patients was 44% (1973–1985), 23% (1986–1998), and 0% (1999–2010). Conclusion: Severe pneumococcal disease is a serious event that is more likely to appear in splenectomised HL patients compared to non-splenectomised, possibly many years after diagnosis. However, the low proportion of deaths in later decades is reassuring, and likely a result of adequate pneumococcal vaccination together with patient and doctor education about the infection risk.

Background Studies concerning reproductive patterns among non-Hodgkin lymphoma (NHL) survivors are scarce and those available have reported conflicting results. Until today, no study has reported reproduction rates for different NHL subtypes despite that treatment regimens and disease activity vary considerably between aggressive and indolent NHL. Hence, research disentangling reproductive patterns of NHL patients by subtype are warranted. Methods In this matched cohort study we identified all NHL patients in Sweden, Denmark, and the south-east health region in Norway who were diagnosed in 2000-2019 and aged 18-40 years at diagnosis. Patients were identified from the Swedish and Danish lymphoma registers, and the clinical data base at Oslo University Hospital. NHLs were categorised according to clinical behaviour as aggressive or indolent, and by histological characteristic as diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), T-NK cell lymphoma and other B-cell lymphomas. Population comparators were matched to each patient on sex, birth year, and country in a 1:10 ratio in Sweden and Denmark, and a 1:5 ratio in Norway. Data on childbirths was obtained from national medical birth registers. Patients and comparators were followed from 9 months after index date (diagnosis or matching date) until date of first childbirth, death, or administrative censoring (December 2017, 2018, or 2019 for Norway, Sweden, and Denmark, respectively, or after 10 years of follow-up). Hazard ratios (HRs) contrasting clinical and histological NHL subtypes to comparators were estimated using Cox regression within time bands allowing for non-proportional hazards. Flexible parametric survival models were used to estimate cause-specific cumulative incidence (CIF) of childbirth, in the presence of death as a competing event, and differences thereof (ΔCIF). A comprehensive analysis plan has been pre-registered on the Open Science Framework (DOI: 10.17605/OSF.IO/A4U3D). Results We included 2,212 NHL patients and 20,709 comparators. Most patients were diagnosed with an aggressive lymphoma (67.9%). The most common histological subtypes were DLBCL (49.2%) and FL (19.4%). Among patients with aggressive and indolent lymphoma, 21.5% and 10.6% were aged between 18 and 25 years at diagnosis, respectively. Results stratified by clinical aggressiveness showed that males and females diagnosed with aggressive lymphoma subtypes had lower reproduction rates than comparators the first 3 years after diagnosis (HRfemale: 0.44, 95% CI:0.32; 0.61, HRmale :0.63, 95% CI: 0.49; 0.81), whereas reproduction patterns among survivors with indolent lymphomas were similar to comparators within the first 3 years after diagnosis among both males and females (HRfemale: 0.68, 95% CI:0.46; 1.00, HRmale: 0.91, 95% CI: 0.67; 1.23). When stratifying by histological subtypes both male and female DLBCL patients had lower reproduction rates the first 3 years after diagnosis (HRfemale: 0.44, 95% CI: 0.30; 0.63, HRmale: 0.63, 95% CI: 0.48; 0.85). Among females, those diagnosed with T-NK cell lymphoma and other B-cell lymphomas showed similar decreases (HRT-NK cell: 0.52, 95% CI: 0.28; 0.96; HROther B-cell: 0.50, 95% CI: 0.26; 0.98). After 3 years reproduction rates of NHL patients reached those of comparators, for both levels of aggressiveness and all histological subtypes. Nevertheless, when contrasted to comparators, the proportion of survivors who had at least one childbirth during follow-up was decreased up to 10 years after diagnosis among individuals with a previous aggressive lymphoma (ΔCIFfemale: -0.06, 95% CI: -0.10; -0.01; ΔCIFmale: -0.04, 95% CI -0.08; -0.00) and those with previous DLBCL (ΔCIFfemale: -0.07, 95% CI -0.11; -0.02; ΔCIFmale: -0.06, 95% CI -0.10; -0.02) (Figure 1). Conclusion Patients with indolent lymphomas have reproductive patterns similar to the general population. Patients with aggressive lymphomas showed decreased reproduction mainly the first years following diagnosis. Nevertheless, the reduced CIF indicates that patients with DLBCL do not reach the reproduction level of comparators even after 10 years. Fertility counselling is therefore particularly important for this patient group. Figure 1 Cause-specific CIF of childbirth across time since diagnosis in the presence of death as competing event among cases and comparators (bottom lines) and differences thereof (ΔCIF) (top line). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract Background Results from previous studies indicate that use of aspirin may improve colorectal cancer (CRC) survival. The aim of this study was to assess whether use of aspirin influences overall survival or CRC‐specific survival in an unselected cohort of patients diagnosed with CRC. Methods The study was performed using the Colorectal Cancer Data Base Sweden (CRCBaSe), a mega‐linkage originating from the Swedish Colorectal Cancer Register, with additional linkages to other national health care registers. All patients diagnosed with primary CRC stage I–III treated with curative surgery, aged 18–85 years at diagnosis, from 2007 through 2016 were identified. Information on low‐dose aspirin use was extracted from the Swedish Prescribed Drug Register. Exposure was defined as dispensed prescription for at least 6 months. Aspirin exposure was analyzed at the time of surgery (yes/no) and as a time‐varying exposure during follow‐up. Follow‐up was restricted to a maximum 6 years, to model 5‐year survival. Cox regression models were fitted to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Adjustments were performed for sex, age, year of diagnosis, Charlson comorbidity index, hypertension, and ASA score as potential confounders. Results A total of 32,195 patients diagnosed with CRC were included. 6764 (21%) were exposed to aspirin at the time of CRC surgery. The median time of follow‐up was 4.2 years. Aspirin use at the time of surgery was not associated with all‐cause (adjusted HR = 1.03, 95% CI: 0.97–1.08) nor CRC‐specific mortality (adjusted HR = 0.99, 95% CI: 0.91–1.07). Aspirin use during follow‐up was associated with increased all‐cause (adjusted HR = 1.09, 95% CI: 1.04–1.15) but not CRC‐specific mortality (adjusted HR = 0.98, 95% CI: 0.91–1.06). A CRC‐specific effect associated with aspirin was noted from approximately 3 years following surgery. Conclusions In this large nation‐wide cohort study there was no convincing association between aspirin use after CRC and OS or CRC‐specific survival.

Background: Early events are associated with inferior outcomes in follicular lymphoma (FL) and increased risk of death due to refractory FL. Risk prediction of early events prior to the start of therapy may enhance clinical management and research strategies. We report the FL International Prognostic Index model developed specifically to predict the risk of event within 24 months (EFS24) of starting first-line immunochemotherapy (IC) (FLIPI24). Methods: Modeling was performed using individual patient data from 10 observational cohorts from Europe, North America, and Australia. Eligible patients were diagnosed with grades 1-3A FL and initiated frontline R-CHOP, R-CVP, R-bendamustine (B-R), or like therapies. Event-free survival (EFS) was defined as time from start of IC to progression, retreatment, transformation, or death due to any cause. Model development utilized a truncated Cox model stratified on IC type and cohort with a time-dependent adjustment for maintenance therapy. Multiple imputation was implemented to address missing data. Functional forms of variables were assessed using splines. Model selection was based on model performance, clinical relevance, and parsimony. Gradient boosting machines were evaluated as a complementary approach and used to inform model selection. Model building was performed on an 80% split sample with 20% held for internal testing. External validation occurred in an independent cohort. FLIPI24 risk scores assumed B-R or R-CHOP based chemotherapy and 50% likelihood of maintenance. Results: 4485 patients initiating frontline IC between 2002 and 2018 were utilized in the analysis; 3577 patients were utilized for model building and 908 for internal model testing. Median age at diagnosis in the model build dataset was 61 years (IQR 53-69) and 51% were male. FLIPI was 21%, 32%, and 48% for low, intermediate, and high risk, respectively. IC type was 1874 R-CHOP or like (52%), 730 B-R or like (20%), and 973 R-CVP (27%); 2164 received CD20 antibody maintenance (61%). At median follow-up of 77 months (IQR 48-115), EFS24 estimate was 81% (95% CI: 79-82) and 835 patients (23%) died. 5-year survival after an early (non-death) event was 46% (95% CI: 42-50). The FLIPI24 model utilizes 5 continuous variables: age (linear 60-90 years with inflection at age 75), hemoglobin (linear 8-17 g/dL), white blood cell count (linear 4-11 109/L), normalized lactate dehydrogenase (linear 0.5-5), and beta-2-microglobulin (linear 1-10 mg/L). Linear variables and valid ranges were utilized based on close examination of functional forms across potential models. Continuous FLIPI24 risk scores were grouped for visualization in K-M curves as follows: very low risk (0-0.10), low risk (0.10-0.15), average risk (0.15-0.20), high risk (0.20-0.40), very high risk (>0.40), Figure 1. Internal validation was performed on the 20% holdout set (N=908). The FLIPI24 had superior concordance (c-stat) for EFS24 (c-stat=0.666) compared to FLIPI (c-stat=0.630) and PRIMA-PI (c-stat=0.590) models, Table 1. Importantly, FLIPI24 also improved prognostic ability for 10-year OS following IC (c-stat = 0.672) vs FLIPI (c-stat=0.629) or PRIMA-PI (c-stat=0.595). External validation was performed in a prospective cohort of 1438 newly diagnosed patients with FL (558 treated with IC) enrolled in the multicenter US LEO Cohort between 2015 and 2020. The FLIPI24 had superior c-stats compared to the FLIPI and PRIMA-PI for EFS24 (0.671 vs 0.600 vs 0.602) and OS (0.732 vs. 0.652 vs 0.635) in IC treated patients and for OS (0.785 vs 0.703 vs 0.662) when assessed in all patients. Conclusion: The FLIPI24 model provides an individual risk score at diagnosis for the likelihood of experiencing an event within 24 months from starting IC. The FLIPI24 was rigorously developed, tested, and externally validated using large harmonized and pooled international observational cohorts from the IC era. The FLIPI24 utilizes objective variables easily and reliably measured at diagnosis. A novel feature of the model is the significance of established blood-based measurements in the model, which appears to capture underlying tumor and host biology. Model performance for FLIPI24 was superior to standard clinical models for prediction of both EFS24 and OS in internal and external validation sets. Elevated FLIPI24 risk represents a patient population for further biologic studies and who should be considered for novel frontline therapies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Survival in mantle cell lymphoma after frontline treatment with R-bendamustine, R-CHOP and the Nordic MCL2 regimen -a real world study on

Figure 1: Aalen-Johansen estimates of the cause-specific cumulative incidence (CIF) of childbirth estimated in the presence of competing risks of death. Background: Reproduction in classical Hodgkin lymphoma (cHL) survivors has been shown to be reduced compared to the general population, likely due to multi-agent chemotherapy. Understanding if contemporary treatment protocols are associated with reduced reproduction is important as treatment guidelines shift towards more liberal use of more intensive chemotherapy. Methods: We identified 2,937 individuals aged 18–40 years with cHL in Swedish and Danish lymphoma registers, and in the clinical database at Oslo University Hospital (OUH) between 1995 and 2019, who were linked to national medical birth registers in each country. Cox regression adjusted for stage, performance status, year and age at diagnosis was used to estimate hazard ratios (HRs) contrasting time to first childbirth by treatment groups (ABVD, 2–4 BEACOPP, 6–8 BEACOPP) up to ten years after diagnosis. Cause-specific cumulative incidence (CIF) of childbirths was further estimated using flexible parametric survival models. All analyses included an interaction between cHL treatment and sex. Results: Overall, 71.4% of patients were treated with ABVD, 3.6% with 2–4 BEACOPP, and 10.3% with 6–8 BEACOPP. The reproduction rates (per 1,000 person-years) were 45.5 (males) and 48.2 (females) in the ABVD group, and 23.8 (males) and 39.9 (females) in the 6–8 BEACOPP group. The adjusted HR comparing reproduction rates in individuals treated with 6–8 BEACOPP to ABVD was 0.51 (95% CI 0.35–0.73) for males and 0.82 (95% CI 0.57–1.19) for females. The CIF after 10 years was 20.0% (CI: 14.7%–27.2%) for males and 33.0% (CI: 24.6%–44.3%) for females treated with 6–8 BEACOPP. Conclusion: We found that BEACOPP treatment is associated with decreased reproduction rates compared to ABVD in male cHL patients. Infertility counselling should be prioritized for this group. This abstract has been accepted and presented at the EHA 2022 congress.