The impact of CHOP versus bendamustine on bone mineral density in patients with indolent lymphoma enrolled in the GALLIUM study.

Standard CHOP treatment includes a high cumulative dose of prednisone, and studies have shown increased fracture risk following CHOP. It is unclear whether reductions in bone mineral density (BMD) are caused by glucocorticoids or by the combination with chemotherapy. Our objective was to determine the effect of obinutuzumab (G)/rituximab (R)-bendamustine versus G/R-CHOP on BMD in follicular lymphoma patients. Patients in this GALLIUM post hoc study were ≥60 years old and in complete remission at induction treatment completion (ITC), following treatment with G or R in combination with bendamustine or CHOP. To assess BMD, Hounsfield units (HU) were measured in lumbar vertebra L1 on annual computed tomography. Furthermore, vertebral compression fractures were recorded. Of 173 patients included, 59 (34%) received CHOP and 114 (66%) received bendamustine. At baseline, there was no difference in HU between groups. The mean HU decrease from baseline to ITC was 27.8 after CHOP and 17.3 after bendamustine, corresponding to a difference of 10.4 (95% CI: 3.2-17.6). Vertebral fractures were recorded in 5/59 patients receiving CHOP and in 2/114 receiving bendamustine. CHOP was associated with a significant greater decrease in BMD and more frequent fractures. These results suggest that prophylaxis against BMD loss should be considered.

High-Dose Methotrexate as CNS Prophylaxis in High-Risk Aggressive B-Cell Lymphoma.

PURPOSE: CNS progression or relapse is an uncommon but devastating complication of aggressive B-cell lymphoma. There is no consensus regarding the optimal approach to CNS prophylaxis. This study was designed to determine whether high-dose methotrexate (HD-MTX) is effective at preventing CNS progression in patients at high risk of this complication. PATIENTS AND METHODS: Patients age 18-80 years with aggressive B-cell lymphoma and high risk of CNS progression, treated with curative-intent anti-CD20-based chemoimmunotherapy, were included in this international, retrospective, observational study. Cause-specific hazard ratios (HRs) and cumulative risks of CNS progression were calculated according to use of HD-MTX, with time to CNS progression calculated from diagnosis for all patients (all-pts) and from completion of frontline systemic lymphoma induction therapy, for patients in complete response at completion of chemoimmunotherapy (CR-pts). RESULTS: Two thousand four hundred eighteen all-pts (HD-MTX; n = 425) and 1,616 CR-pts (HD-MTX; n = 356) were included. CNS International Prognostic Index was 4-6 in 83.4% all-pts. Patients treated with HD-MTX had a lower risk of CNS progression (adjusted HR, 0.59 [95% CI, 0.38 to 0.90]; P = .014), but significance was not retained when confined to CR-pts (adjusted HR, 0.74 [95% CI, 0.42 to 1.30]; P = .29), with 5-year adjusted risk difference of 1.6% (95% CI, -1.5 to 4.4; all-pts) and 1.4% (95% CI, -1.5 to 4.1; CR-pts). Subgroups were underpowered to draw definitive conclusions regarding the efficacy of HD-MTX in individual high-risk clinical scenarios; however, there was no clear reduction in CNS progression risk with HD-MTX in any high-risk subgroup. CONCLUSION: In this large study, high-risk patients receiving HD-MTX had a 7.2% 2-year risk of CNS progression, consistent with the progression risk in previously reported high-risk cohorts. Use of HD-MTX was not associated with a clinically meaningful reduction in risk of CNS progression.

Reproduction patterns among non-Hodgkin lymphoma survivors by subtype in Sweden, Denmark and Norway: A population-based matched cohort study.

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.

Reproduction patterns among classical Hodgkin lymphoma survivors treated with BEACOPP and ABVD in Sweden, Denmark and Norway-A population-based matched cohort study.

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.

An International Comparison of Presentation, Outcomes and CORONET Predictive Score Performance in Patients with Cancer Presenting with COVID-19 across Different Pandemic Waves.

Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants.

Establishment of CORONET, COVID-19 Risk in Oncology Evaluation Tool, to Identify Patients With Cancer at Low Versus High Risk of Severe Complications of COVID-19 Disease On Presentation to Hospital.

PURPOSE: Patients with cancer are at increased risk of severe COVID-19 disease, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction, and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 disease in patients with cancer predicting severe disease and build a decision support online tool, COVID-19 Risk in Oncology Evaluation Tool (CORONET). METHODS: Patients with active cancer (stage I-IV) and laboratory-confirmed COVID-19 disease presenting to hospitals worldwide were included. Discharge (within 24 hours), admission (≥ 24 hours inpatient), oxygen (O2) requirement, and death were combined in a 0-3 point severity scale. Association of features with outcomes were investigated using Lasso regression and Random Forest combined with Shapley Additive Explanations. The CORONET model was then examined in the entire cohort to build an online CORONET decision support tool. Admission and severe disease thresholds were established through pragmatically defined cost functions. Finally, the CORONET model was validated on an external cohort. RESULTS: The model development data set comprised 920 patients, with median age 70 (range 5-99) years, 56% males, 44% females, and 81% solid versus 19% hematologic cancers. In derivation, Random Forest demonstrated superior performance over Lasso with lower mean squared error (0.801 v 0.807) and was selected for development. During validation (n = 282 patients), the performance of CORONET varied depending on the country cohort. CORONET cutoffs for admission and mortality of 1.0 and 2.3 were established. The CORONET decision support tool recommended admission for 95% of patients eventually requiring oxygen and 97% of those who died (94% and 98% in validation, respectively). The specificity for mortality prediction was 92% and 83% in derivation and validation, respectively. Shapley Additive Explanations revealed that National Early Warning Score 2, C-reactive protein, and albumin were the most important features contributing to COVID-19 severity prediction in patients with cancer at time of hospital presentation. CONCLUSION: CORONET, a decision support tool validated in health care systems worldwide, can aid admission decisions and predict COVID-19 severity in patients with cancer.

Multiplex proteomics as risk predictor of infection in patients treated with hemodialysis-A prospective multicenter study.

INTRODUCTION: Severe infection is a major problem in hemodialysis patients. Multiplex proteomics might reveal novel insights into disease mechanisms increasing the risk of infection and might also be used as a risk prediction tool. The aims of this study were (1) to evaluate associations between 92 proteins assessed by a proximity extension assay and the development of severe infection in patients on hemodialysis and (2) to develop a risk prediction model for severe infection using prespecified clinical variables and proteomics. METHODS: Prospective, observational multicenter cohort study with 5-year follow-up. Patients receiving in-center hemodialysis in five facilities in Denmark were included. The primary composite endpoint was death caused by infection, bacteremia, and infections requiring hospitalization of at least 2 days or prolonging a hospital stay. FINDINGS: Of 331 patients included 210 patients reached the primary endpoint during follow-up. In adjusted Cox regression analyses, 14 plasma proteins were associated with severe infection. Correcting for multiple testing revealed only cathepsin-L1 and interleukin-6 significantly associated with the primary outcome. Cathepsin-L1-hazard ratio: 1.64 (95% confidence interval [CI] 1.24-2.17) and interleukin-6-hazard ratio: 1.16 (95% CI 1.05-1.29). Apparent C-statistics of the risk prediction model using clinical variables was 0.605, addition of cathepsin-L1 and interleukin-6 to the model improved discrimination slightly: C = 0.625. DISCUSSION: Proteomic profiling identified cathepsin-L1 and interleukin-6 as markers for infectious risk in hemodialysis patients. Further studies are needed to replicate the results and to examine possible causality. The developed risk prediction models need considerable improvement before implementation in clinical practice is meaningful.

Parenthood Rates and Use of Assisted Reproductive Techniques in Younger Hodgkin Lymphoma Survivors: A Danish Population-Based Study.

PURPOSE: The majority of young adults with Hodgkin lymphoma (HL) are cured, but chemotherapy-induced infertility can have profound psychosocial consequences. Providing data on parenthood rates and use of assisted reproductive techniques (ARTs) after contemporary HL treatment is important for patient counseling and survivorship care. MATERIALS AND METHODS: All Danish patients with HL diagnosed during 2000-2015 at the ages 18-40 years who achieved remission after first-line therapy were included and matched on age, sex, and parenthood status to five random persons from the general population. Parenthood rates were defined as the rate of first live birth per 1,000 person years, starting 9 months after HL diagnosis. Nationwide birth and patient registers were used to capture parenthood outcomes and ARTs use. RESULTS: A total of 793 HL survivors and 3,965 comparators were included (median follow-up 8.7 years). Similar parenthood rates were observed for male and female HL survivors when compared with matched comparators (56.2 v 57.1; P = .871 for males and 63.8 v 61.2; P = .672 for females). For male HL survivors, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) therapy was associated with lower parenthood rates as compared to the matched comparators (28.1 v 60.8; P = .020). Live birth after ARTs were more common for HL survivors than for comparators (males 21.6% v 6.3%; P < .001; females 13.6% v 5.5%; P = .001). There were no differences in gestational age, Apgar score, or newborn measurements between HL survivors and matched comparators. CONCLUSION: The parenthood rates for HL survivors who have not experienced relapse were generally similar to the general population. However, ARTs were used more often before the first live birth in HL survivors, which is relevant information when discussing possible long-term side effects and fertility-preserving treatment options.

Relapsed/Refractory International Prognostic Index (R/R-IPI): An international prognostic calculator for relapsed/refractory diffuse large B-cell lymphoma.

Disease progression after frontline therapy for Diffuse large B-cell lymphoma (DLBCL) is a clinically significant event. Patients who experience early progression or have refractory disease have especially poor outcomes. Simple, clinically applicable prognostic tools are needed for selecting patients for consideration for novel therapies and prognostication in the relapsed/refractory (R/R) setting. Model building was performed in patients from the Surrogate endpoints in aggressive lymphoma (SEAL) consortium with disease progression after frontline immunochemotherapy. The primary endpoint was overall survival (OS) measured from date of progression. Validation was performed in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) and Danish National Lymphoma Register (LYFO) cohorts. Model performance was assessed using time-dependent concordance indices (c-statistic) and calibration with metrics evaluated at 2 years from progression. Note, 1234 of 5112 patients treated with frontline immunochemotherapy in the SEAL consortium developed progressive disease. Time to progression on immunochemotherapy and age at progression were strongly associated with post-progression OS (both p < 0.001). A prognostic model was developed incorporating spline fit for both variables. The model had good concordance in the discovery (0.67) and validation sets (LYFO c = 0.64, MER c = 0.68) with generally good calibration. Time to progression on frontline therapy is strongly associated with post-progression OS in DLBCL. We developed and validated a simple to apply clinical prognostic tool in the R/R setting. The useful prediction of expected outcomes in R/R DLBCL and can inform treatment decisions such as considerations for CAR-T therapy as well as trial designs. The model is available in smartphone-based point of care applications.

Burkitt Lymphoma International Prognostic Index.

PURPOSE: Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches. METHODS: We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019. RESULTS: In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase > 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively. CONCLUSION: The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.

SARS-CoV-2 infection among patients with haematological disorders: Severity and one-month outcome in 66 Danish patients in a nationwide cohort study.

OBJECTIVES: Patients with haematological disorders may be particularly vulnerable to respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, this is unknown. METHODS: We conducted a prospective, nationwide study including 66 patients in follow-up at Danish haematology departments with a malignant or non-malignant haematological disorder and with verified SARS-CoV-2 infection. Outcomes were intensive care unit (ICU) admission and one-month survival rate. RESULTS: Mean age was 66.7 years, 60.6% were males, 90.9% had comorbidity, and 13.6% had a BMI ≥ 30. The most frequent diagnoses were chronic lymphocytic leukaemia/lymphoma (47.0%), multiple myeloma (16.7%) and acute leukaemia/myelodysplastic syndrome (AL/MDS) (12.1%). Treatment for the haematological disease was ongoing in 59.1% of cases. Neutropenia was present in 6.5%, lymphopenia in 46.6% and hypogammaglobulinaemia in 26.3%. The SARS-CoV-2 infection was mild in 50.0%, severe in 36.4% and critical in 13.6%. After one month, 21.2% had been admitted to ICU, and 24.2% died. Mortality was highest in older patients, patients with severe/critical SARS-CoV-2 infection, high comorbidity score or high performance status score, purine analogue treatment and with AL/MDS. Although older patients and patients with comorbidities had the highest mortality rates, mortality was considerable among all haematological patients. CONCLUSION: Haematological patients with SARS-CoV-2 infection has a severe clinical course.

Depression and anxiety in Hodgkin lymphoma patients: A Danish nationwide cohort study of 945 patients.

Cancer-related psychological distress may lead to depression and anxiety among survivors. The vast majority of patients with Hodgkin lymphoma (HL) become long-term survivors, but the risk of mental health problems after HL is not well-characterized. Using national population-based registries, we investigated the cumulative incidence of psychotropic drug (antidepressants, antipsychotics, and anxiolytics) use (proxies for depression and anxiety) in HL patients as well as if an increased risk would normalize over time for patients in remission. The study included 945 HL patients aged 18-92 years and 4725 matched persons. In total, 215 HL patients (22.8%) received a prescription of any psychotropic drug (PD) at some point after date of diagnosis compared to 545 persons (11.5%) in the matched cohort. Cumulative incidences with death/relapse as competing risk confirmed that HL patients were at higher risk of receiving psychotropic drug prescriptions, but the increased risk was transient and normalized to the matched population 5 years into survivorship. Increased age, Eastern Cooperative Oncology Group performance status, and disease stage were associated with higher risk of psychotropic drug prescriptions. Given the increased rate of psychotropic drug prescriptions after HL diagnosis, screening for symptoms of depression and anxiety is warranted after HL diagnosis and first years into survivorship.

On estimating the time to statistical cure.

BACKGROUND: The mortality risk among cancer patients measured from the time of diagnosis is often elevated in comparison to the general population. However, for some cancer types, the patient mortality risk will over time reach the same level as the general population mortality risk. The time point at which the mortality risk reaches the same level as the general population is called the cure point and is of great interest to patients, clinicians, and health care planners. In previous studies, estimation of the cure point has been handled in an ad hoc fashion, often without considerations about margins of clinical relevance. METHODS: We review existing methods for estimating the cure point and discuss new clinically relevant measures for quantifying the mortality difference between cancer patients and the general population, which can be used for cure point estimation. The performance of the methods is assessed in a simulation study and the methods are illustrated on survival data from Danish colon cancer patients. RESULTS: The simulations revealed that the bias of the estimated cure point depends on the measure chosen for quantifying the excess mortality, the chosen margin of clinical relevance, and the applied estimation procedure. These choices are interdependent as the choice of mortality measure depends both on the ability to define a margin of clinical relevance and the ability to accurately compute the mortality measure. The analysis of cancer survival data demonstrates the importance of considering the confidence interval of the estimated cure point, as these may be wide in some scenarios limiting the applicability of the estimated cure point. CONCLUSIONS: Although cure points are appealing in a clinical context and has widespread applicability, estimation remains a difficult task. The estimation relies on a number of choices, each associated with pitfalls that the practitioner should be aware of.

Minimal relapse risk and early normalization of survival for patients with Burkitt lymphoma treated with intensive immunochemotherapy: an international study of 264 real-world patients.

Non-endemic Burkitt lymphoma (BL) is a rare germinal centre B-cell-derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunochemotherapy, retrospective clinic-based and population-based lymphoma registries from six countries were used to identify 264 real-world patients. The median age was 47 years and the majority had advanced-stage disease and elevated LDH. Treatment protocols were R-CODOX-M/IVAC (47%), R-hyper-CVAD (16%), DA-EPOCH-R (11%), R-BFM/GMALL (25%) and other (2%) leading to an overall response rate of 89%. The two-year overall survival and event-free survival were 84% and 80% respectively. For patients in complete remission/unconfirmed, the two-year relapse risk was 6% but diminished to 0·6% for patients reaching 12 months of post-remission event-free survival (pEFS12). The loss of lifetime for pEFS12 patients was 0·4 (95% CI: -0·7 to 2) months. In conclusion, real-world outcomes of adult BL are excellent following intensive immunochemotherapy. For pEFS12 patients, the relapse risk was low and life expectancy similar to that of a general population, which is important information for developing meaningful follow-up strategies with increased focus on survivorship and less focus on routine disease surveillance.

Risk of death, relapse or progression, and loss of life expectancy at different progression-free survival milestones in primary central nervous system lymphoma.

In this study, we analyzed the evolution of the prognosis of primary central nervous system lymphoma (PCNSL) patients as they reach selected progression-free survival (PFS) milestones after high-dose methotrexate (HD-MTX)-based therapy. In total, 258 and 146 patients were included from Denmark and British Columbia, respectively. All patients were diagnosed during 2000-2017. The 5-year PFS was 27% (95% CI 23; 32); however, for patients reaching 5 years of PFS, this increased to 71% (95% CI 57; 86). Within the first 5 years after diagnosis, patients lost 2.0 years (95% CI 1.8; 2.2) when compared to a similar background population. This reduced to 0.5 years (95% CI 0.2; 0.9) for patients reaching 5 years of PFS. Treatment with rituximab was associated with improved outcomes. The prognosis of patients with PCNSL treated with HD-MTX-based regimens in this cohort is poor, although it improves as patients survive without progression/relapse. However, survival does not conclusively normalize to that of a similar background population.

Estimating the loss of lifetime function using flexible parametric relative survival models.

BACKGROUND: Within cancer care, dynamic evaluations of the loss in expectation of life provides useful information to patients as well as physicians. The loss of lifetime function yields the conditional loss in expectation of life given survival up to a specific time point. Due to the inevitable censoring in time-to-event data, loss of lifetime estimation requires extrapolation of both the patient and general population survival function. In this context, the accuracy of different extrapolation approaches has not previously been evaluated. METHODS: The loss of lifetime function was computed by decomposing the all-cause survival function using the relative and general population survival function. To allow extrapolation, the relative survival function was fitted using existing parametric relative survival models. In addition, we introduced a novel mixture cure model suitable for extrapolation. The accuracy of the estimated loss of lifetime function using various extrapolation approaches was assessed in a simulation study and by data from the Danish Cancer Registry where complete follow-up was available. In addition, we illustrated the proposed methodology by analyzing recent data from the Danish Lymphoma Registry. RESULTS: No uniformly superior extrapolation method was found, but flexible parametric mixture cure models and flexible parametric relative survival models seemed to be suitable in various scenarios. CONCLUSION: Using extrapolation to estimate the loss of lifetime function requires careful consideration of the relative survival function outside the available follow-up period. We propose extensive sensitivity analyses when estimating the loss of lifetime function.

Bilirubin isomer distribution in jaundiced neonates during phototherapy with LED light centered at 497 nm (turquoise) vs. 459 nm (blue).

BACKGROUND: Phototherapy using blue light is the treatment of choice worldwide for neonatal hyperbilirubinemia. However, treatment with turquoise light may be a desirable alternative. Therefore, the aim of this randomized, controlled study was to compare the bilirubin isomer distribution in serum of jaundiced neonates after 24 h of therapy with narrow-band (LED) light centered at 497 nm (turquoise) vs. 459 nm (blue), of essentially equal irradiance. MATERIALS: Eighty-three neonates (≥33 wk gestational age) with uncomplicated hyperbilirubinemia were included in the study. Forty neonates were exposed to light centered at 497 nm and 43 infants with light centered at 459 nm. Irradiances were 5.2 × 10(15) and 5.1 × 10(15) photons/cm(2)/s, respectively. RESULTS: After 24 h of treatment no significant differences in serum concentrations of total bilirubin isomers and Z,Z-bilirubin were observed between the 2 groups. Interestingly, concentrations of Z,E-bilirubin, and thus also total bilirubin isomers formed during therapy, were highest for infants receiving light centered at 459 nm, while the concentration of E,Z-bilirubin was highest for those receiving light centered at 497 nm. No significant difference was found between concentrations of E,Z-lumirubin. CONCLUSION: Therapy with LED light centered at 497 nm vs. 459 nm, applied with equal irradiance on the infants, resulted in a different distribution of bilirubin isomers in serum.

No survival benefit associated with routine surveillance imaging for Hodgkin lymphoma in first remission: a Danish-Swedish population-based observational study.

The use of routine imaging for patients with classical Hodgkin lymphoma (HL) in complete remission (CR) is controversial. In a population-based study, we examined the post-remission survival of Danish and Swedish HL patients for whom follow-up practices were different. Follow-up in Denmark included routine imaging, usually for a minimum of 2 years, whereas clinical follow-up without routine imaging was standard in Sweden. A total of 317 Danish and 454 Swedish comparable HL patients aged 18-65 years, diagnosed in the period 2007-2012 and having achieved CR following ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)/BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) therapy, were included in the study. The cumulative progression rates in the first 2 years were 4% (95% confidence interval [CI] 1-7) for patients with stage I-II disease vs. 12% (95% CI 6-18) for patients with stage III-IV disease. An imaging-based follow-up practice was not associated with a better post-remission survival in general (P = 0·2) or in stage-specific subgroups (P = 0·5 for I-II and P = 0·4 for III-IV). Age ≥45 years was the only independent adverse prognostic factor for survival. In conclusion, relapse of HL patients with CR is infrequent and systematic use of routine imaging in these patients does not improve post-remission survival. The present study supports clinical follow-up without routine imaging, as encouraged by the recent Lugano classification.