Knut Bjøro Smeland

Concerns about treatment‐related fertility impairment are common among young adult lymphoma survivors. Evidence on the impact of treatment for aggressive non‐Hodgkin lymphoma (NHL) on future childbearing is limited, although many individuals of reproductive age are affected. This matched cohort study identified male (18–52 years) and female (18–40 years) patients with aggressive NHL between 2007 and 2018 in Sweden and the south‐east health‐care region in Norway, and matched lymphoma‐free comparators. Adjusted hazard ratios (aHRs) comparing childbirth rates in patients treated with primary intensive chemoimmunotherapy (CIT) (e.g., R‐CHOEP and R‐DA‐EPOCH) to standard‐of‐care (R‐CHOP), and to comparators, were estimated using Cox regression. Among 1037 young survivors of aggressive NHL, childbirth rates did not differ significantly by treatment intensity (intensive vs. standard CIT) in females (aHR: 0.61, 95% CI: 0.32–1.13) or males (aHR: 1.20, 95% CI: 0.68–2.09), overall or when stratified by time since diagnosis (< 3 and 3–10 years). However, females treated with intensive CIT had lower childbirth rates than comparators during the first 3 years after diagnosis (aHR: 0.52, 95% CI: 0.30–0.88), but not thereafter (aHR: 1.06, 95% CI: 0.57–1.96). A similar pattern was not seen in males. In Sweden, eight children (three with support from assisted reproductive techniques) were born after stem cell transplantation. In conclusion, childbirth rates did not differ by CIT intensity among survivors of aggressive NHL. Although rates were temporarily reduced in females during the treatment and recovery period after diagnosis, subsequent rates were similar to comparators. These findings provide reassurance, while highlighting the importance of early and ongoing fertility counseling.

Molecular tumor boards are supported by clinical decision support system (CDSS) tools for the interpretation of complex molecular data towards personalized treatments. Current CDSS tools are genomics-focused and characterized by tight couplings between data ingestion, guideline-based reasoning logic and curated knowledgebases. Next-generation CDSS solutions should integrate multimodal data and learn from outcomes in an interoperable ecosystem, leveraging explainable, trustworthy output from AI models through rigorous clinical validation processes.

Hodgkin lymphoma survivors (HLSs) are at risk of developing late effects (LEs), and their knowledge is crucial for prevention and treatment. We explored HLSs' knowledge and experience with LEs, their needs for information about LEs, lifestyle and rehabilitation, their needs for long-term follow-up, and factors associated with these needs. HLSs, treated from 1997 to 2006, aged < 49 years at diagnosis, were invited to this Norwegian cross-sectional questionnaire-based study performed in 2018/19. Medical records provided information on histology, stage, and treatment. Descriptive statistics and logistic regression analyses were employed. In total, 304 responded (59% response rate), median age at diagnosis was 29 years (range 8-49), median age at survey was 46 (21-70), and 48% were females. Ninety percent had classical HL, 62% stage I-IIA disease, 94% received chemotherapy, and 77% radiotherapy. Thirty-two percent had experienced 1-2 LEs, and 40% ≥ 3 LEs. Information about lifestyle and/or rehabilitation was requested by 64%, and 58% wanted follow-up for LEs. In the multivariable analysis, lower education (OR 2.3, 95% CI 1.3-4.0), chronic fatigue (CF) (OR 2.3, 1.3-4.3), and physical inactivity (OR 2.1, 1.2-3.7) were associated with need for information on lifestyle and/or rehabilitation. CF (OR 2.4, 1.3-4.2) and received radiotherapy (OR 2.8, 1.5-5.3) were associated with the need for follow-up. A high proportion of HLSs report LEs, and about 60% report a need for information and follow-up. Our findings contribute to the ongoing discussion on how to best organize cancer survivorship care. CF is associated with both information needs and follow-up, indicating that these survivors could benefit from a structured follow-up programme.

Background and purpose: There are few studies of personality traits in long-term Hodgkin lymphoma survivors (HLSs) treated according to contemporary stage-and risk-adapted approaches. The Distressed Personality (DP) Scale covers negative affectivity and social inhibition. We examined differences in self-reported late adverse effects (LAEs) between HLSs with and without DP and other explanatory variables. Material and methods: This cross-sectional questionnaire-based study included a population-based cohort of HLSs treated from 1997 to 2006, aged 8–49 years at diagnosis, and alive in 2016. Among 518 eligible HLSs, 303 responded (58%), and 294 completed the DP scale. DP was defined by scores above cut-off on both the negative affectivity and social inhibition subscales. LAEs studied were major depression, posttraumatic stress disorder, sleep problems, obesity, neuropathy, fatigue, memory problems, and general health. DP and 10 other explanatory variables were tested against LAEs as dependent variables in multivariable regression analyses. Results: The mean age at survey was 45.9 years (standard deviation [SD] 4.6), mean follow-up time 16.7 years (SD 3.0), and 48% were females. Eighty-two HLSs had DP (28%, 95% confidence interval 23% – 33%). All LAEs except obesity were significantly more common/had higher mean score in HLSs with DP. In multivariable analyses, presence of DP was significantly associated with all LAEs except obesity. Interpretation: The presence of DP is common among HLSs. The presence of DP was associated with most self-report LAEs examined. Including assessment of personality traits in the survivorship care plans of HLSs should be considered. Prospective studies assessing the influence of pretreatment DP on LAEs are warranted.

PURPOSE: Patients diagnosed with advanced-stage Hodgkin lymphoma (aHL) have historically been risk-stratified using the International Prognostic Score (IPS). This study investigated if a machine learning (ML) approach could outperform existing models when it comes to predicting overall survival (OS) and progression-free survival (PFS). PATIENTS AND METHODS: This study used patient data from the Danish National Lymphoma Register for model development (development cohort). The ML model was developed using stacking, which combines several predictive survival models (Cox proportional hazard, flexible parametric model, IPS, principal component, penalized regression) into a single model, and was compared with two versions of IPS (IPS-3 and IPS-7) and the newly developed aHL international prognostic index (A-HIPI). Internal model validation was performed using nested cross-validation, and external validation was performed using patient data from the Swedish Lymphoma Register and Cancer Registry of Norway (validation cohort). RESULTS: In total, 707 and 760 patients with aHL were included in the development and validation cohorts, respectively. Examining model performance for OS in the development cohort, the concordance index (C-index) for the ML model, IPS-7, IPS-3, and A-HIPI was found to be 0.789, 0.608, 0.650, and 0.768, respectively. The corresponding estimates in the validation cohort were 0.749, 0.700, 0.663, and 0.741. For PFS, the ML model achieved the highest C-index in both cohorts (0.665 in the development cohort and 0.691 in the validation cohort). The time-varying AUCs for both the ML model and the A-HIPI were consistently higher in both cohorts compared with the IPS models within the first 5 years after diagnosis. CONCLUSION: The new prognostic model for aHL on the basis of ML techniques demonstrated a substantial improvement compared with the IPS models, but yielded a limited improvement in predictive performance compared with the A-HIPI.

High-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT) is the preferred treatment option in relapsed or refractory Hodgkin lymphoma (HL). We analyzed the association between treatment intensity and health-related quality of life (HRQoL), depressive symptoms, and chronic fatigue (CF) in long-term survivors of HL (HLS), identified in two population-based national cross-sectional studies on late adverse effects. We included 375 HLS treated between 1987 and 2006, 264 with conventional therapy only, and 111 with HDT-ASCT. Despite similar differences to the matched general population, when controlling for other imbalances between the groups, use of HDT-ASCT was not associated with poorer outcome in multivariable analysis. However, work participation, family income, comorbidities, and lifestyle factors had stronger associations with aspects of HRQoL, depressive symptoms, and CF. Our data suggest that better rehabilitation to work participation and adequate income as well as follow-up for comorbidities may reduce differences in long-term outcome after treatment for HL.

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.