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Purpose: Etoposide to standard R‐CHOP is used for high‐risk diffuse large B‐cell lymphoma (DLBCL) in some countries. Due to the lack of randomized trials, a real‐world data study using matching methods was used to test the potential effectiveness of R‐CHOEP over R‐CHOP. Patients and Methods: This study included patients from the Danish Lymphoma Register diagnosed between 2006 and 2020 at the age of 18–60 years with de novo DLBCL and age‐adjusted IPI ≥2. R‐CHOEP treated patients were matched 1:1 without replacement to R‐CHOP treated patients using a hybrid exact and genetic matching technique. Primary endpoints were progression‐free survival (PFS) and overall survival (OS). Results: In total, 396 patients were included; 213 received R‐CHOEP and 183 received R‐CHOP. Unadjusted 5‐year PFS and OS for R‐CHOEP were 69% (95% Confidence intervals [CI]; 63%–76%) and 79% (CI;73%–85%) versus 62% (CI;55%–70%) and 76% (CI;69%–82%) for R‐CHOP (log‐rank test, PFS p =.25 and OS p =.31). A total of 127 patients treated with R‐CHOEP were matched to 127 patients treated with R‐CHOP. Matching‐adjusted 5‐year PFS and OS were 65% (CI; 57%–74%) and 79% (CI; 72%–84%) for R‐CHOEP versus 63% (CI; 55%–73%) and 79% (CI;72%–87%) for R‐CHOP (log‐rank test, PFS p =.90 and OS p =.63). Conclusion: The present study did not confirm superiority of R‐CHOEP over R‐CHOP for young patients with high‐risk DLBCL. [ABSTRACT FROM AUTHOR]

Summary: Cardiovascular diseases, especially congestive heart failure (CHF), are known complications of anthracyclines, but the risk for patients undergoing high‐dose chemotherapy and autologous stem cell transplant (HDT‐ASCT) is not well established. With T‐cell therapies emerging as alternatives, studies of long‐term complications after HDT‐ASCT are warranted. Danish patients treated with HDT‐ASCT for aggressive lymphoma between 2001 and 2017 were matched 1:5 on sex, birth year and Charlson comorbidity score to the general population. Events were captured using nationwide registers. A total of 787 patients treated with HDT‐ASCT were identified. Median follow‐up was 7.6 years. The risk of CHF was significantly increased in the HDT‐ASCT population compared to matched comparators with an adjusted hazard ratio (HR) of 5.5 (3.8–8.1). The 10‐year cumulative incidence of CHF was 8.0% versus 2.0% (p < 0.001). Male sex, ≥2 lines of therapy, hypertension and cumulative anthracycline dose (≥300 mg/m2) were risk factors for CHF. In a separate cohort of 4089 lymphoma patients, HDT‐ASCT was also significantly associated with increased risk of CHF (adjusted HR of 2.6 [1.8–3.8]) when analysed as a time‐dependent exposure. HDT‐ASCT also increased the risk of other cardiac diseases. These findings are applicable for the benefit/risk assessment of HDT‐ASCT versus novel therapies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (HRfemale: 0.43, 95% CI: 0.31–0.59, HRmale: 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 (HRfemale: 0.71, 95% CI: 0.48–1.04, HRmale: 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. [ABSTRACT FROM AUTHOR]

The deployment of machine learning for tasks relevant to complementing standard of care and advancing tools for precision health has gained much attention in the clinical community, thus meriting further investigations into its broader use. In an introduction to predictive modelling using machine learning, we conducted a review of the recent literature that explains standard taxonomies, terminology and central concepts to a broad clinical readership. Articles aimed at readers with little or no prior experience of commonly used methods or typical workflows were summarised and key references are highlighted. Continual interdisciplinary developments in data science, biostatistics and epidemiology also motivated us to further discuss emerging topics in predictive and data‐driven (hypothesis‐less) analytics with machine learning. Through two methodological deep dives using examples from precision psychiatry and outcome prediction after lymphoma, we highlight how the use of, for example, natural language processing can outperform established clinical risk scores and aid dynamic prediction and adaptive care strategies. Such realistic and detailed examples allow for critical analysis of the importance of new technological advances in artificial intelligence for clinical decision‐making. New clinical decision support systems can assist in prevention and care by leveraging precision medicine. [ABSTRACT FROM AUTHOR]

Summary: Several recently published trials investigate novel therapies for relapsed/refractory diffuse large B‐cell lymphoma (R/R DLBCL). To estimate the benefit of these therapies in the real‐world setting, comprehensive data on patients treated in clinical routine are needed. We report outcomes for 736 R/R DLBCL patients identified among all curatively treated DLBCL patients in Sweden in the period 2007–2014. Survival and associations with disease characteristics, second‐line treatment and fulfilment of chimaeric antigen receptor (CAR) T‐cell trial criteria were assessed. Median overall survival (OS) was 6.6 months (≤70 years 9.6 months, >70 years 4.9 months). Early relapse (≤12 months) was strongly associated with selection of less intensive treatment and poor survival. Among patients of at most 70 years of age, 63% started intensive second‐line treatment and 34% received autologous stem cell transplantation (ASCT). Two‐year OS among transplanted patients was 56% (early relapse ≤12 months 40%, late relapse >12 months 66%). A minority of patients 76 years (n = 178/506, 35%) fitted CAR T trial criteria. Median progression‐free survival (PFS) for patients with early relapse fitting trial criteria was 4.8 months. In conclusion, most R/R DLBCL manifest early and are often ineligible for or cannot complete intensive regimens resulting in dismal survival. Real‐world patients eligible for CAR T trials also did poorly, providing a benchmark for efficacy of novel therapies. [ABSTRACT FROM AUTHOR]

Summary: Statin use has been associated with reduced mortality from several cancers but also suggested, in vitro, to diminish the effectiveness of lymphoma treatments including rituximab. The present study aimed to assess the association of statin use with mortality in patients with non‐Hodgkin lymphoma (NHL) and chronic lymphocytic leukaemia (CLL). We identified all incident NHLs and CLLs in Sweden from 2007 to 2013 with subtype information in the Swedish Lymphoma and Cancer Registers. Using Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of pre‐ or post‐diagnosis statin use (yes/no, intensity) with lymphoma‐specific, cardiovascular, or all‐cause mortality; and for follicular lymphoma (FL) by initial treatment strategy (active/watch‐and‐wait). Among 16 098 incident NHL/CLL patients, 20% used statins at diagnosis. Pre‐ and post‐diagnosis statin use, and statin intensity were not consistently associated with any mortality outcome in patients with NHL, overall or for any subtype. For actively treated patients with FL, statin use did not appear to increase lymphoma‐specific mortality (vs. non‐users, HR [95% CI]after diagnosis 0·87 [0·45–1·67]). For CLL, statin use was associated with all‐cause and cardiovascular but not consistently with lymphoma‐specific mortality. In conclusion, statin use was not associated with improved lymphoma survival but appears safe to use during lymphoma treatment. [ABSTRACT FROM AUTHOR]

As cancer patient survival improves, late effects from treatment are becoming the next clinical challenge. Chemotherapy and radiotherapy, for example, potentially increase the risk of both morbidity and mortality from second malignancies and cardiovascular disease. To provide clinically relevant population‐level measures of late effects, it is of importance to (1) simultaneously estimate the risks of both morbidity and mortality, (2) partition these risks into the component expected in the absence of cancer and the component due to the cancer and its treatment, and (3) incorporate the multiple time scales of attained age, calendar time, and time since diagnosis. Multistate models provide a framework for simultaneously studying morbidity and mortality, but do not solve the problem of partitioning the risks. However, this partitioning can be achieved by applying a relative survival framework, allowing us to directly quantify the excess risk. This article proposes a combination of these two frameworks, providing one approach to address (1) to (3). Using recently developed methods in multistate modeling, we incorporate estimation of excess hazards into a multistate model. Both intermediate and absorbing state risks can be partitioned and different transitions are allowed to have different and/or multiple time scales. We illustrate our approach using data on Hodgkin lymphoma patients and excess risk of diseases of the circulatory system, and provide user‐friendly Stata software with accompanying example code. [ABSTRACT FROM AUTHOR]

Summary: There is a lack of data regarding treatment and prognosis for the growing group of oldest old patients with lymphoma. Therefore, we studied 2347 patients aged ≥85 years from the Danish and Swedish lymphoma registers 2000–2016 (Denmark) and 2007–2013 (Sweden). Outcome was assessed using relative survival (RS). The 2‐year RS overall for patients with aggressive lymphomas was 38% [95% confidence interval (CI) 35–42%], of whom 845 (66%) patients received active treatment (chemotherapy, radiotherapy, immunotherapy, other). For aggressive lymphomas, not receiving active treatment was associated with an inferior 2‐year RS of 12% (95% CI 9–17%) compared to 49% (95% CI 45–53%) for patients who received active treatment (excess mortality rate ratio 2·84, 95% CI 2·3–3·5; P < 0·0001). For patients with indolent lymphoma, the 2‐year RS was 77% (95% CI 72–82%). Here, 383 (46%) patients received active treatment at diagnosis, but did not have better 2‐year RS (75%, 95% CI 67–81%) compared to those who did not receive active treatment (83%, 95% CI 74–89%). We conclude that outcomes for the oldest old patients with lymphoma are encouraging for several subtypes and that active treatment is associated with improved outcome amongst the oldest old patients with aggressive lymphomas, indicating that age itself should not be a contraindication to treatment. [ABSTRACT FROM AUTHOR]

Objectives: To investigate concordance in survival time among first‐degree relatives with lymphoid malignancies. Methods: By linkage of national Swedish registers, we identified 66 430 patients diagnosed with a lymphoid malignancy 1958‐2016 with information on first‐degree relationships and follow‐up until 2017. Among these, we identified pairs of first‐degree relatives with any (N = 3326) or a similar (N = 690) lymphoid malignancy subtype. We defined survival in the first‐degree relative as good, expected, or poor based on tertiles of deviance residuals from a multivariable Cox regression model. Next, we used Cox regression to estimate hazard ratios (HR) of death with 95% confidence intervals (CI) among patients, using the survival of their first‐degree relative as exposure and adjusting for confounders. Results: There was no concordance in survival among first‐degree relatives with any lymphoid malignancy (HRgood = 1.00 (reference), HRExpected = 1.02, 95% CI: 0.89‐1.17, HRPoor = 1.12, 95% CI: 0.98‐1.27, Ptrend =.08). Among first‐degree relatives with indolent lymphoma, including chronic lymphocytic leukemia, those with a first‐degree relative to an expected or poor survival had worse outcome compared to those with a first‐degree relative with good survival (HRExpected = 1.44, 95% CI: 0.82‐2.53, HRPoor = 1.79, 95% CI: 1.07‐3.00, Ptrend =.03). Conclusion: Our results support a role of inherited factors in the outcome of indolent lymphoma, including chronic lymphocytic leukemia. [ABSTRACT FROM AUTHOR]

Summary: Non‐Hodgkin lymphoma (NHL) prognosis has improved in recent years, yet the number of patients living with the diagnosis, i.e. the prevalence, has seldom been reported. The prevalence provides a measure of the burden of disease, useful for healthcare planning and to optimise resource allocation. We provide a systematic presentation of temporal trends in absolute numbers of prevalent patients by NHL subtypes, linking them to trends in incidence, survival and mortality. Patients diagnosed 2000–2016 were identified in the national Swedish lymphoma register. Incidence and mortality rates, relative survival and prevalence were estimated for NHL overall and for major clinical and morphological subtypes. Poisson regression was used to test for temporal trends. Increasing incidence and improved survival have led to a 47% increase in the five‐year prevalence of NHL overall in 2016 compared to 2004. An increasing prevalence was observed for all investigated subtypes during the study period, but most notably for diffuse large B cell lymphomas among aggressive subtypes (66%), and marginal zone lymphomas among indolent subtypes (135%). This dramatic increase in NHL prevalence underscores the need to develop and evaluate alternative follow‐up schemes to use resources efficiently and still ensure optimal care of lymphoma survivors. [ABSTRACT FROM AUTHOR]

Summary: The prognosis for mantle cell lymphoma (MCL) remains poor. Our aim was to assess the impact of comorbidities on survival and causes of death. For 1,385 MCL patients (1,009 males, 376 females) diagnosed in 2000–2014 (median age 71 years, range 22–96) comorbidities ≤ 10 years of diagnosis were classified according to the Charlson comorbidity index (CCI; 0, 1, 2+). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to compare lymphoma‐specific and all‐cause mortality rates. Model‐based predictions were used to obtain probabilities of death. Overall, 44% had any comorbidity (CCI 1+) and 28% severe comorbidity (CCI 2+). Over a median follow‐up of 3·7 years (range 0–16), 633 (46%) died, the majority (76%) from lymphoma. Severe comorbidity was independently associated with higher all‐cause [hazard ratio (HR) = 1·52; 95% CI: 1·24–1·85) and lymphoma‐specific mortality (HR = 1·31; 95% CI: 1·04–1·65). Particularly among patients with connective tissue, renal and psychiatric diseases, and dementia. Among females with any comorbidity, non‐lymphoma deaths represented a larger proportion of all deaths, compared to males with any comorbidity. In general, more efficient lymphoma treatments need to be considered also for patients with severe comorbidity. However, among females with any comorbidity, the likelihood of non‐lymphoma death was still considerable, perhaps favouring a more liberal use of a "wait and watch" approach. [ABSTRACT FROM AUTHOR]

Solid organ transplant recipients (OTRs) have an increased cancer risk but their survival once diagnosed with cancer has seldom been assessed. We therefore investigated cancer‐specific survival among OTRs with a wide range of cancer forms nationally in Sweden. The study included 2,143 OTRs with cancer, and 946,089 nontransplanted cancer patients diagnosed 1992–2013. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models adjusted for age, sex and calendar year. Median follow‐up was 3.1 (range 0–22) years. Overall, OTRs diagnosed with any cancer had a 35% higher rate of cancer death compared to nontransplanted cancer patients (HR: 1.35, 95% CI: 1.24–1.47). Specifically, higher rates of cancer‐specific death were observed among OTRs diagnosed with Hodgkin lymphoma (HR: 15.0, 95% CI: 5.56–40.6), high‐grade non‐Hodgkin lymphoma (HR: 2.68, 95% CI: 1.90–3.77), malignant melanoma (HR: 2.80, 95% CI: 1.74–4.52) and urothelial (HR: 2.56, 95% CI: 1.65–3.97), breast (HR: 2.12, 95% CI: 1.38–3.25), head/neck (HR: 1.55, 95% CI: 1.02–2.36) and colorectal (HR: 1.42, 95% CI: 1.07–1.88) cancer. The worse outcomes were not explained by differences in distribution of cancer stage or histologic subtypes. For other common cancer forms such as prostate, lung and kidney cancer, the prognosis was similar to that in nontransplanted cancer patients. In conclusion, several but not all types of posttransplantation cancer diagnoses are associated with worse outcomes than in the general population. Reasons for this should be further explored to optimize posttransplantation cancer management. What's new? While cancer risk increases significantly following solid organ transplant, little is known about cancer‐specific survival in transplant recipients. Here, analyses of survival among post‐transplant and non‐transplanted cancer patients in Sweden reveal significantly increased rates of death among transplant recipients diagnosed with certain cancer types, including Hodgkin lymphoma and melanoma and cancers of the breast and colorectal tract. Differences in stage or histologic subtype did not account for worse prognosis of these cancers. Common cancers, such as prostate and kidney cancer, had similar prognosis in the two groups. The findings could have implications for post‐transplantation cancer management and screening. [ABSTRACT FROM AUTHOR]

While Hodgkin lymphoma (HL) survival has improved, treatment‐related complications remain a concern. As a measure of treatment‐related diseases of the circulatory system (DCS) we report excess incidence of DCS and absolute risks among HL patients diagnosed in the modern treatment era. From the Swedish Cancer Register, we identified all HL patients diagnosed 1985 through 2013, at ages 18–80 years. Excess incidence rate ratios (EIRRs) with 95% confidence intervals (CIs) comparing excess DCS incidence between calendar periods were estimated overall, and at 5 and 10 years after diagnosis using flexible parametric models. Model‐based predictions were used to obtain probabilities of being diagnosed with DCS, in the presence of competing risks. During follow‐up, 726 (16%) of the 4,479 HL patients experienced DCS. Overall, the excess DCS incidence was lower during all calendar periods compared to the first (2009–2013 vs. 1985–1988: EIRR = 0.63, 95% CI: 0.42–0.95). The 5‐ and 10‐year excess incidence of DCS decreased between 1985 and 1994 for 25‐year‐olds (5‐year‐EIRR1994 = 0.32, 95% CI: 0.12–0.92) and 60‐year‐olds (5‐year‐EIRR1994 = 0.45, 95% CI: 0.24–0.88), but remained stable thereafter. No improvements were observed among 75‐year‐olds. The probability of excess DCS remained the same throughout the study period. In 2009, the percentage of patients aged 25, 60 and 75 experiencing excess DCS within 5 years was 3.4, 15.0 and 17.0% (males) and 2.3, 10.8 and 12.6% (females). Treatment‐related incidence of DCS has declined since the mid‐1980s, but more recent improvements are absent and an excess risk remains. Continued efforts towards less toxic treatments are warranted, alongside primary prevention strategies. What's new? Treatment for Hodgkin lymphoma saves lives, but also leads to additional, treatment‐related diseases. Here, the authors calculated the excess risk of diseases of the circulatory system (DCS) experienced by HL patients, compared with the risk expected for patients who have not had HL. Looking at patients diagnosed between 1985‐2013, they found that incidence of treatment‐related DCS decreased from 1985 through 1994, but leveled off after that. Patients treated since 2000 have elevated risk of a treatment‐related DCS for up to 10 years. Less toxic treatment, or better prevention strategies, would be worth pursuing. [ABSTRACT FROM AUTHOR]

The burden of late effects among Hodgkin lymphoma (HL) survivors treated according to contemporary protocols remains poorly characterized. We used nation‐wide registers to assess number of inpatient bed‐days and specialist outpatient visits among 1048 HL‐patients (<25 years, diagnosed 1990‐2010) and 5175 country‐, sex‐, and age‐matched comparators. We followed them for up to 24 years, with time‐dependent assessment of relapse status. International Classification of Diseases (ICD‐10) chapter‐specific hazard ratios (HRs) were assessed in Cox regression analyses, and nonparametric statistics described patterns of health‐care‐use. Relative to comparators, relapse‐free survivors were at increased risk of infections, diseases of the blood, endocrine, circulatory and respiratory systems, and unspecific symptoms, HRs ranging from 1.86 to 3.05. Relative to comparators, relapsed survivors had at statistically significantly increased risk of diseases reflecting practically all investigated disease‐chapters, HRs ranging from 1.60 to 18.7. Among relapse‐free survivors, 10% of the patients accounted for 80% of all hospital bed days, and 55% were never hospitalized during follow‐up. Among relapsed‐survivors, 10% of the patients accounted for 50% of the bed days, and only 24% were never hospitalized during follow‐up. In contrast, 10% of the comparators accounted for 90% of hospital bed days and 75% were never hospitalized. These findings challenge the impression of a uniformly distributed long‐term morbidity among all HL survivors and emphasize the need for early identification and attention to patients particularly susceptible to late effects, such as relapsed survivors. [ABSTRACT FROM AUTHOR]

The international prognostic index (IPI) and similar models form the cornerstone of clinical assessment in newly diagnosed diffuse large B- cell lymphoma (DLBCL). While being simple and convenient to use, their inadequate use of the available clinical data is a major weakness. In this study, we compared performance of the International Prognostic Index (IPI) and its variations (RIPI and NCCN-IPI) to a Cox proportional hazards (CPH) model using the same covariates in nondichotomized form. All models were tested in 4863 newly diagnosed DLBCL patients from population- based Nordic registers. The CPH model led to a substantial increase in predictive accuracy as compared to conventional prognostic scores when evaluated by the area under the curve and other relevant tests. Furthermore, the generation of patient- specific survival curves rather than assigning patients to one of few predefined risk groups is a relevant step toward personalized management and treatment. A test- version is available on lymphomapredictor.org. [ABSTRACT FROM AUTHOR]

Objectives This study aims to characterize the epidemiology of immunocompetent Primary central nervous system lymphoma ( PCNSL) diagnosed 2000-2013 in Sweden. Methods Cases were identified in the population-based Swedish Lymphoma Register. Incidence per 100 000 person-years and 95% confidence intervals ( CI) were calculated, and PCNSL-specific survival was estimated using relative survival. Tests for temporal trends were performed using Poisson regression. Population incidence of all brain tumors was retrieved for comparison. Results With 359 identified PCNSL cases (median age 66 years), overall incidence was 0.26 (95% CI: 0.24-0.29) and the average annual increase 4% ( P = .002). The increasing trend was primarily observed among elderly individuals (70+ years). Similarly, an increase in incidence of all brain tumors was noted only among the elderly. There was no significant improvement in relative survival across the study period although, among fit patients (with Eastern Cooperative Oncology Group, EGOC 0), survival plateaued 6 years after diagnosis. Conclusion The increasing PCNSL incidence in the elderly was consistent with an increasing incidence of brain tumors of any type and may in part be attributable to improved diagnostics and reporting in this group. New treatment options have not yet translated into general survival improvements in a population-based setting, although the presence of long-term survivors among fit patients is encouraging. [ABSTRACT FROM AUTHOR]

The prognostic value of detailed anatomic site and ultraviolet radiation (UVR) exposure patterns has not been fully determined in cutaneous melanoma. Thus, we reviewed medical records for detailed site in a population-based retrospective Swedish patient cohort diagnosed with primary invasive melanoma 1976-2003 ( n = 5,973). We followed the patients from date of diagnosis until death, emigration or December 31st 2013, and evaluated melanoma-specific survival by subsite in a multivariable regression model adjusting for established prognostic factors. We found that melanoma on chronic UVR exposure sites (face, dorsum of hands; adjusted HR 0.6; CI 0.4-0.7) and moderately intermittent UVR sites (lateral arms, lower legs, dorsum of feet; HR 0.7; CI 0.6-0.8) were associated with a favorable prognosis compared with highly intermittent sites (chest, back, neck, shoulders and thighs). Further, melanoma on poorly visible skin sites upon self-examination (scalp, retroauricular area, back, posterior upper arms and thighs, buttocks, pubic area; HR 1.3; CI 1.1-1.5) had a worse prognosis than those on easily visible sites (face, chest, abdomen, anterior upper arms and thighs, lower arms and legs, dorsum of hands and feet, palms). In conclusion, highly intermittent UVR exposure sites and poor skin visibility presumably correlate with reduced melanoma survival, independent of established tumor characteristics. A limitation of the study was the lack of information on actual individual UVR exposure. [ABSTRACT FROM AUTHOR]

In recent decades, the prognosis of Mantle Cell Lymphoma ( MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 11·4 years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 12·7 and 8·5 years, respectively. The MCL International Prognostic Index ( MIPI), biological MIPI, including Ki67 expression ( MIPI-B) and the MIPI-B including mIR-18b expression ( MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12 years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL. [ABSTRACT FROM AUTHOR]

Cancer incidence, survival and mortality are essential population-based indicators for public health and cancer control. Confusion and misunderstanding still surround the estimation and interpretation of these indicators. Recurring controversies over the use and misuse of population-based cancer statistics in health policy suggests the need for further clarification. In our article, we describe the concepts that underlie the measures of incidence, survival and mortality, and illustrate the synergy between these measures of the cancer burden. We demonstrate the relationships between trends in incidence, survival and mortality, using real data for cancers of the lung and breast from England and Sweden. Finally, we discuss the importance of using all three measures in combination when interpreting overall progress in cancer control, and we offer some recommendations for their use. [ABSTRACT FROM AUTHOR]

A useful summary measure for survival data is the expectation of life, which is calculated by obtaining the area under a survival curve. The loss in expectation of life due to a certain type of cancer is the difference between the expectation of life in the general population and the expectation of life among the cancer patients. This measure is used little in practice as its estimation generally requires extrapolation of both the expected and observed survival. A parametric distribution can be used for extrapolation of the observed survival, but it is difficult to find a distribution that captures the underlying shape of the survival function after the end of follow-up. In this paper, we base our extrapolation on relative survival, because it is more stable and reliable. Relative survival is defined as the observed survival divided by the expected survival, and the mortality analogue is excess mortality. Approaches have been suggested for extrapolation of relative survival within life-table data, by assuming that the excess mortality has reached zero (statistical cure) or has stabilized to a constant. We propose the use of flexible parametric survival models for relative survival, which enables estimating the loss in expectation of life on individual level data by making these assumptions or by extrapolating the estimated linear trend at the end of follow-up. We have evaluated the extrapolation from this model using data on four types of cancer, and the results agree well with observed data. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We aimed to investigate if characteristics of contralateral breast cancer (CBC) are influenced by adjuvant radiotherapy for the first breast cancer. Using information from population-based registers and medical records, we analyzed two cohorts comprising all women with CBC diagnosed >3 months after their first cancer (809 patients in Stockholm 1976-2005 and 750 patients in South Sweden 1977-2005). We used Poisson regression to calculate risk of distant metastasis after CBC, comparing patients treated and not treated with radiotherapy for the first cancer. Logistic regression was used to estimate odds ratio (OR) of more aggressive tumor characteristics in the second cancer, compared to the first. For patients with CBC in Stockholm with <5 years between the cancers radiotherapy for the first cancer conferred a nearly doubled risk of distant metastasis [incidence rate ratio (IRR) = 1.91; 95% confidence interval (CI): 1.27-2.88], compared to those not treated with radiotherapy. This was replicated in the South Swedish cohort [IRR = 2.12 (95% CI: 1.40-3.23)]. In Stockholm, we found an increased odds that, following radiotherapy, a second cancer was of more advanced TNM-stage [OR 2.16 (95% CI 1.13-4.11)] and higher histological grade [OR = 2.00 (95% CI 1.08-3.72)] compared to the first, for patients with CBC with <5 years between the cancers. No effect on any of the investigated outcomes was seen for patients diagnosed with CBC >5 years from the first cancer. In conclusion, patients diagnosed with CBC within 5 years had worse prognosis and more aggressive tumor characteristics of the second cancer, if they had received radiotherapy for their first cancer, compared to no radiotherapy. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPV) are established as a major cause of cervical carcinoma. However, causality inference is dependent on prospective evidence showing that exposure predicts risk for future disease. Such evidence is available for squamous cell carcinoma, but not for cervical adenocarcinoma. We followed a population-based cohort of 994,120 women who participated in cytological screening in Sweden for a median of 6.7 years. Baseline smears from women who developed adenocarcinoma during follow-up (118 women with in situ disease and 164 with invasive disease) and their individually matched controls (1,434 smears) were analyzed for HPV using PCR. Conditional logistic regression was used to estimate odds ratios (OR) of future adenocarcinoma with 95% confidence intervals (CI). Being positive for HPV 16 in the first cytologically normal smear was associated with increased risks for both future adenocarcinoma in situ (OR: 11.0, 95% CI: 2.6-46.8) and invasive adenocarcinoma (OR: 16.0, 95% CI: 3.8-66.7), compared to being negative for HPV 16. Similarly, an HPV 18 positive smear was associated with increased risks for adenocarcinoma in situ (OR: 26.0, 95% CI: 3.5-192) and invasive adenocarcinoma (OR: 28.0, 95% CI: 3.8-206), compared to an HPV 18 negative smear. Being positive for HPV 16/18 in 2 subsequent smears was associated with an infinite risk of both in situ and invasive adenocarcinoma. In conclusion, infections with HPV 16 and 18 are detectable up to at least 14 years before diagnosis of cervical adenocarcinoma. Our data provide prospective evidence that the association of HPV 16/18 with cervical adenocarcinoma is strong and causal. [ABSTRACT FROM AUTHOR]

BACKGROUND: Disquieting reports of increased complication and death rates after transfusions of red blood cells (RBCs) stored for more than 14 days prompted us to perform an observational retrospective cohort study of mortality in relation to storage time. STUDY DESIGN AND METHODS: We conducted a cohort study utilizing data on all recipients of at least one RBC transfusion in Sweden and Denmark between 1995 and 2002, as recorded in the Scandinavian Donations and Transfusions (SCANDAT) database. Relative risks of death in relation to storage time were estimated using Cox regression, adjusted for several possible confounding factors. RESULTS: After various exclusions, 404,959 transfusion episodes remained for analysis. The 7-day risk of death was similar in all exposure groups, but a tendency for a higher risk emerged among recipients of blood stored for 30 to 42 days (hazard ratio, 1.05; 95% confidence interval [CI], 0.97-1.12), compared to recipients of blood stored for 10 to 19 days. With 2-year follow-up, this excess remained at the same level (hazard ratio, 1.05; 95% CI, 1.02-1.08). No dose-response pattern was revealed and no differential effect was seen when the analyses were restricted to recipients of leukoreduced units only. CONCLUSION: Although a small excess mortality was noted in recipients of the oldest RBCs, the risk pattern was more consistent with weak confounding than with an effect of the momentary exposure to stored RBCs. It seems, thus, that any excess mortality conferred by older RBCs in the combined Swedish and Danish transfusion recipient population is likely less than 5%, which is considerably smaller than in the hitherto largest investigation. [ABSTRACT FROM AUTHOR]

Large age-dependant differences in temporal trends in 1- and 5-year relative survival have been observed in patients with acute myeloid leukaemia (AML) in Sweden. This investigation used an alternative approach to studying patient survival that simultaneously estimated the proportion of patients cured from their cancer and the survival of the ‘uncured’. We conducted a population-based study including 6439 AML patients aged 19–80 years in Sweden between 1973 and 2001. Mixture cure models were estimated, with age at diagnosis categorised (19–40, 41–60, 61–70 and 71–80) and year of diagnosis modelled using splines. In 1975 the cure proportion was ≤6% in all age groups and the median survival time for ‘uncured’ patients was <0·5 years. In 2000 the cure proportion was 68% (95% confidence interval 56–77%) in the youngest group, and 32% (25–39%), 8% (3–21%), and 4% (2–8%) in the other groups, respectively. The median survival times for ‘uncured’ were 0·74 (0·43–1·26), 0·71 (0·53–0·97), 0·69 (0·51–0·95) and 0·37 (0·31–0·44) years, respectively. A dramatic improvement in the cure proportion was seen in younger patients, whereas improvement in older ages was mainly within the survival of the ‘uncured’. This novel approach of analysing survival data could be a valuable tool for physicians, patients, health care planners and health economists. [ABSTRACT FROM AUTHOR]

Highlights from the article: We have read the commentary by Dr Acuna and Dr Dossa in response to our article published in the International Journal of Cancer.[1] We agree with the authors that competing risks analysis is indeed a topic that often leads to confusion and misinterpretation. The primary objective of the study in question was to investigate if organ transplant recipients (OTR) have a worse cancer-specific survival as compared to cancer patients without a history of organ transplantation. Studies that aim to estimate absolute risks of cancer death in the presence of competing risks among OTRs would, nevertheless, add an interesting extension to our study, as well as others who have arrived at similar conclusions regarding the net survival of these patients.[5].

The article presents a continuing medical education program (CME) activity in transfusion, for which the article "Duration of red blood cell storage and survival of transfused patients," published within the issue has been selected. The goal of the activity is to maintain current and practical knowledge of important clinical issues, discuss complications in blood transfusion and describe the standard of practice for blood donors.