Ingrid Glimelius

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.

Objective: Retroperitoneal lymph node dissection (RPLND) for testicular germ cell cancer is a complex procedure associated with postoperative complications and long-term morbidity, best performed by experienced surgeons at high-volume centers. This study evaluates surgical outcomes of RPLND in a centralized population-based cohort. Methods: This is a retrospective analysis of a prospective multicenter cohort of all RPLNDs in Sweden between 2018 and 2022. 217 patients (175 nonseminomas and 42 seminomas) underwent unilateral or bilateral primary RPLND or post-chemotherapy RPLND. Primary outcomes were complications, loss of ejaculation, and histopathology. Results: Intraoperative complications occurred in 8% of unilateral and 0% of bilateral templates in primary RPLND, and in 0 and 8% in post-chemotherapy RPLND, most commonly renal injury. Postoperative complications rate was significantly higher with bilateral templates in post-chemotherapy RPLND (49% vs 18%, p < 0.01). Clavien-Dindo ≥ IIIb complications occurred in 2 (primary) and 3% (post-chemotherapy), respectively. Loss of ejaculation was numerically more common after bilateral templates (primary: 60% vs 31%, p = 0.07; post-chemotherapy: 53% vs 38%, p = 0.09). Viable cancer was found in 95% of seminomas and 52% of nonseminomas for primary RPLND and in nonseminoma post-chemotherapy RPLND, 11% viable cancer, 50% teratoma, and 39% benign nodes. Robotic surgery did not increase complications or loss of ejaculation. Conclusions: RPLND demonstrated low complication rates and rare serious events. Bilateral templates were associated with increased loss of ejaculation. Robotic surgery was safe, and prior chemotherapy did not preclude laparoscopy. Post-chemotherapy RPLND showed more teratoma and viable cancer, and fewer benign findings than previously reported.

No universal gold standard chemotherapy exists for the treatment of older (≥60 years) patients with classical Hodgkin lymphoma (cHL). To evaluate the current curative treatment strategies used in the Nordic countries, we collected data from patients diagnosed in Sweden, Denmark and Norway during the years 2000 to 2021. We included 1569 patients: 704 (45%) Swedish, 671 (43%) Danish and 194 (12%) Norwegian. Of these, 671 (43%) received doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), 123 (8%) received doxorubicin, vinblastine, dacarbazine (AVD), 465 (31%) received cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and 212 (13%) received other chemotherapy (single agent or combination). Eighty-two patients (5%) lacked information on first line regimen. In multivariable analyses of overall survival (OS), treatment with AVD was associated with improved survival compared to ABVD, whereas there was a trend toward inferior survival among patients receiving CHOP or other regimens. For progression-free survival (PFS), multivariable analysis likewise demonstrated significantly improved outcome with AVD relative to ABVD, while outcomes for the CHOP group were comparable to ABVD. Outcome for patients receiving other regimens tended to be poorer. Collectively, outcome for AVD with respect to both OS and PFS was at least equal to ABVD and often superior to CHOP. By omitting bleomycin, treatment-related toxicity is known to be reduced in AVD compared to ABVD. Based on our findings, AVD is a preferable chemotherapy option in older cHL patients and should rightly be considered as backbone in treatment with novel drugs.

Second primary malignancies (SPMs) increasingly affect mantle cell lymphoma (MCL) survivors. In nationwide Danish and Swedish cohorts (2000-2020), we evaluated overall survival among MCL patients with SPMs versus matched non-lymphoma individuals with comparable malignancies and MCL patients without SPMs, respectively. Of 3094 MCL survivors, 19% in Denmark and 15% in Sweden developed an SPM, with a median of three years from MCL diagnosis to first SPM. MCL patients with SPMs had about double the mortality risk compared with non-lymphoma counterparts (pooled HR 2.1, 95% confidence interval (CI) 1.3-3.5), and worse survival than MCL patients without SPMs (pooled HR 1.6, 95% CI 1.4-1.9). In Swedish MCL patients with SPMs, deaths were attributed to subsequent hematologic malignancies (9%), solid cancers (14%), primary MCL (23%), non-cancer causes (11%), with 40% still alive. Development of SPMs in MCL is associated with substantially higher mortality, supporting long-term surveillance and proactive management of late complications.

Current epidemiological thinking is that classic Hodgkin lymphoma (cHL) comprises multiple aetiologically distinct disease entities that may in part be defined by either histological subtype or the presence of Epstein–Barr virus (EBV) in the malignant cells, or by both. This study aimed to advance our understanding of epidemiological differences between cHL subtypes, in particular EBV‐positive and EBV‐negative cHL. We retrospectively collected and EBV‐typed 1992 cHL primary tumour tissues from among all 2811 patients diagnosed with incident HL in Denmark in the period 1990 through 2010 ‘Hodgkin lymphoma in Denmark’ [HOLYDAN] project. Based on characteristics of retrieved samples combined with additional information from national registers, we projected nationwide age‐, sex‐, histology‐ and EBV‐specific cHL incidence rates. The analyses demonstrated age‐ and sex‐dependent variation in histology‐ and EBV‐tumour status‐specific cHL incidence rates, details of which yielded new aetiological clues. cHL incidence increased markedly around the age of puberty, irrespective of histological subtype and EBV status. The incidence of all subtypes of cHL increased with age after age 50 years, with the exception of EBV‐negative nodular sclerosis cHL in females, which therefore showed a single peak in incidence and was higher than in males among young adults. These results were obtained in a small homogeneous population and might, therefore, only apply to rich, industrialised, Western populations. Nevertheless, we propose that puberty creates an immunological host environment conducive to cHL development irrespective of EBV status and histology, and that age‐related decline in immune function facilitates the development of both EBV‐positive and EBV‐negative cHL.

Background: World-wide consensus is lacking regarding patient selection and timing of high-dose chemotherapy (HDCT) with autologous stem-cell support in males with germ cell cancer (GCC). However, within the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) guidelines are harmonised. Our aim was to evaluate survival and toxicity in HDCT-treated GCC-patients within SWENOTECA. Methods: In total, 7322 GCC patients were diagnosed between 2011–2021 in Sweden and Norway, among which 80 ( ~ 1.1%) patients were treated with HDCT. Indications for HDCT were: Delayed tumour-marker decline during primary/intensified primary treatment ( n = 45), progressive disease ( n = 29), or relapse ( n = 25). The HDCT-regimen consisted of two cycles of carboplatin/etoposide. Results: The 5-year overall survival (5-yr OS) and progression-free survival (5-yr PFS) after HDCT was 55% and 43%, respectively. Indication delayed tumour-marker decline: 5-yr OS:75%, 5-yr PFS:53%, indication progressive disease 5-yr OS:29%, 5-yr PFS:18%, indication relapse 5-yr OS:61%, 5-yr PFS:58%. Four (5%) died due to HDCT-related complications, none within the delayed tumour-marker decline group. Grade 3–4 infections were seen in n = 69, 86%. Conclusion: HDCT-treatment according to the SWENOTECA-programme was feasible and associated with promising OS. Early intensification to HDCT for patients with delayed tumour-marker decline during primary-treatment was safe and led to 5-yr OS of 75% with no toxic deaths.