Distressed personality is associated with late adverse effects in long-term survivors of Hodgkin lymphoma.

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.

Overall survival and causes of death in elderly patients with Hodgkin lymphoma: a Norwegian population-based case-control study.

Elderly Hodgkin Lymphoma (HL) patients are poorly characterized and underrepresented in studies. In this national population-based study, we investigated cause-specific survival using competing-risk analysis in elderly HL patients compared to the normal population. Patients ≥ 60 years diagnosed between 2000-2015 were identified by Cancer Registry of Norway, records reviewed in detail and compared to data from Norwegian Cause of Death Registry for patients and cancer-free controls. Of 492 patients, 81 (17%) were ineligible for treatment directed specifically towards HL, mostly because of an underlying other lymphoma entity, whereas 74 (15%) and 337 (69%) were treated with palliative or curative intent, respectively. Median overall survival in patients ineligible for assessment of HLdirected therapies was 0.5 years (95% confidence interval [CI] 0.4-0.6), and for palliatively and curatively treated patients 0.8 (0.4-1.2) and 9.1 (7.5-10.7) years, respectively. After correction of discrepancies in registry data, with 359 deaths, 108 (30%) died of HL, the most common cause of death. In curatively treated patients, treatment-related mortality was 6.5% and the risk-difference of dying from HL compared to controls was 28% (95% CI 23-33%) after 10 years. These numbers indicate disease control in a majority of elderly patients eligible for curative treatment, compared to risk-differences for death from HL of 59% (48-71%) and 42% (31-53%) after 10 years in the palliative and ineligible groups, respectively. There was an increased risk of dying from hematological malignancies other than HL in all groups, but not from other competing causes of death, showing no excess mortality from long-term treatment complications.

Chronic fatigue in long-term survivors of Hodgkin's lymphoma after contemporary risk-adapted treatment.

BACKGROUND: Chronic fatigue (CF), substantial fatigue for ≥ six months, can manifest as a late effect (LE) after cancer treatment, and may affect several aspects of life. In a Norwegian cohort of Hodgkin's lymphoma survivors (HLS), more than a decade after contemporary risk-adapted treatment regimens with limited use of radiotherapy (RT), we assessed: (1) Prevalence of, (2) factors associated with (3) and implications of CF on socioeconomic status (SES) and work ability (WA). MATERIAL AND METHODS: HLS treated between 1997-2006, aged 8-49 years at diagnosis, were invited to participate in a population-based cross-sectional study on late effects in 2018-2019. In a mailed questionnaire, HLS responded to a fatigue questionnaire (FQ), work ability score (WAS) and short-form health survey (SF-36). Disease- and treatment data were extracted from hospital records. Factors associated with CF were identified by uni- and multivariate analysis. To study the implications of CF on SES and WA, a multinomial regression analysis was performed. RESULTS: Invitations were extended to 518 HLS and 298 (58%) responded to FQ, of whom 42% had CF with mean (standard deviation [SD]) physical- and mental fatigue scores of 10.2 (4.3) and 5.5 (2.1) respectively. Median age at survey was 45 years, 47% were females. In multivariate analysis female sex (p = 0.03), lower education (p = 0.03), body mass index ≥30 kg/m2 (p = 0.04), and an increasing number of comorbidities (p = 0.01) were associated with CF. No association with disease stage, chemotherapy or RT was found. CF was associated with poorer WAS scores at survey (p < 0.001), unemployment (p = 0.03), and receiving disability pension (p = 0.003). CONCLUSION: After risk-adapted treatment, CF is still a frequent LE among long-term HLS, without apparent association with disease or treatment-related parameters. CF is associated with reduced WA and SES. As no apparent risk reduction is seen with contemporary treatment, further studies should emphasize etiological factors of CF and treatment to alleviate this common LE.

Total late effect burden in long-term lymphoma survivors after high-dose therapy with autologous stem-cell transplant and its effect on health-related quality of life.

Lymphoma survivors after high-dose therapy with autologous stem-cell transplant (HDT-ASCT) are at risk of several late effects, which might impair their health-related quality of life (HRQoL). We assessed the total late effect burden in this population, and how it affects HRQoL. All lymphoma survivors treated with HDT-ASCT as adults in Norway between 1987 and 2008 were identified, and 271 (68%) attended both a comprehensive clinical assessment and completed a questionnaire. Severity of 45 conditions in 12 organ-system categories were graded as mild, moderate, severe or life-threatening, according to a modified version of CTCAEv4.03. At a median of 8 years after HDT-ASCT, 98% of survivors had at least one moderate or more severe late effect and 56% had severe or life-threatening late effects. Fourteen percent had low, 39% medium and 47% high late effect burden, defined as having moderate or more severe late effects in 0-1, 2-3 and >3 organsystems, respectively. Female sex, increasing age, B-symptoms at diagnosis and >1 treatment line prior to HDT-ASCT were independently associated with having high late effect burden. The survivors had significantly poorer physical and mental HRQoL assessed by the Short Form-36 compared to age- and sex-matched controls. The prevalence of poor physical and mental HRQoL increased with higher late effect burden (both P<0.001), and the low burden group had better physical HRQoL than controls (P<0.001). In conclusion, lymphoma survivors after HDT-ASCT have impaired HRQoL, seemingly driven by a high late effect burden. This highlights the importance of prevention, regular assessments for early detection and treatment of late effects and modifiable risk factors.

Prognostic value of combined MTV and ADC derived from baseline FDG PET/MRI in aggressive non-Hodgkins lymphoma.

PURPOSE: The aim of this prospective study was to investigate the prognostic value of metabolic tumor volume (MTV) and apparent diffusion coefficient (ADC) from baseline FDG PET/MRI compared to established clinical risk factors in terms of progression free survival (PFS) at 2 years in a cohort of diffuse large B-cell Lymphoma (DLBCL) and high-grade-B-cell lymphoma (HGBCL). METHODS: Thirty-three patients and their baseline PET/MRI examinations were included. Images were read by two pairs of nuclear medicine physicians and radiologists for defining lymphoma lesions. MTV was computed on PET, and up to six lymphoma target lesions with restricted diffusion was defined for each PET/MRI examination. Minimum ADC (ADCmin) and the corresponding mean ADC (ADCmean) from the target lesion with the lowest ADCmin were included in the analyses. For the combined PET/MRI parameters, the ratio between MTV and the target lesion with the lowest ADCmin (MTV/ADCmin) and the corresponding ADCmean (MTV/ADCmean) was calculated for each patient. Clinical, histological, and PET/MRI parameters were compared between the treatment failure and treatment response group, while survival analyses for each variable was performed by using univariate Cox regression. In case of significant variables in the Cox regression analyses, Kaplan-Meier survival analyses with log-rank test was used to study the effect of the variables on PFS. RESULTS: ECOC PS scale ≥2 (p = 0.05) and ADCmean (p = 0.05) were significantly different between the treatment failure group (n = 6) and those with treatment response (n = 27). Survival analyses showed that ADCmean was associated with PFS (p = 0.02, [HR 2.3 for 1 SD increase]), while combining MTV and ADC did not predict outcome. In addition, ECOG PS ≥2 (p = 0.01, [HR 13.3]) and histology of HGBCL (p = 0.02 [HR 7.6]) was significantly associated with PFS. CONCLUSIONS: ADCmean derived from baseline MRI could be a prognostic imaging biomarker for DLBCL and HGBCL. Baseline staging with PET/MRI could therefore give supplementary prognostic information compared to today's standard PET/CT.

A comparison of FDG PET/MR and PET/CT for staging, response assessment, and prognostic imaging biomarkers in lymphoma.

The aim of the current study was to investigate the diagnostic performance of FDG PET/MR compared to PET/CT in a patient cohort including Hodgkins lymphoma, diffuse large B-cell lymphoma, and high-grade B-cell lymphoma at baseline and response assessment. Sixty-one patients were examined with FDG PET/CT directly followed by PET/MR. Images were read by two pairs of nuclear medicine physicians and radiologists. Concordance for lymphoma involvement between PET/MR and the reference standard PET/CT was assessed at baseline and response assessment. Correlation of prognostic biomarkers Deauville score, criteria of response, SUVmax, SUVpeak, and MTV was performed between PET/MR and PET/CT. Baseline FDG PET/MR showed a sensitivity of 92.5% and a specificity 97.9% compared to the reference standard PET/CT (κ 0.91) for nodal sites. For extranodal sites, a sensitivity of 80.4% and a specificity of 99.5% were found (κ 0.84). Concordance in Ann Arbor was found in 57 of 61 patients (κ 0.92). Discrepancies were due to misclassification of region and not lesion detection. In response assessment, a sensitivity of 100% and a specificity 99.9% for all sites combined were found (κ 0.92). There was a perfect agreement on Deauville scores 4 and 5 and criteria of response between the two modalities. Intraclass correlation coefficient (ICC) for SUVmax, SUVpeak, and MTV values showed excellent reliability (ICC > 0.9). FDG PET/MR is a reliable alternative to PET/CT in this patient population, both in terms of lesion detection at baseline staging and response assessment, and for quantitative prognostic imaging biomarkers.

Post-treatment work patterns amongst survivors of lymphoma treated with high-dose chemotherapy with autologous stem-cell transplantation.

BACKGROUND: This study describes post-treatment work patterns in lymphoma survivors treated with high-dose chemotherapy with autologous stem-cell transplantation (HDT-ASCT). It aims to identify determinants for labour force participation and exclusion after HDT-ASCT. METHODS: All survivors treated with HDT-ASCT for lymphoma in Norway between 1995 and 2008, aged ≥18 years at HDT-ASCT and alive at survey in 2012-2013 were eligible. We divide survivors by current employment status (full-time, part-time and unemployed). Main outcomes are current employment status, work hours and work ability. Withdrawals are patients employed when diagnosed but not before HDT-ASCT. RESULTS: Of the 274 who completed the survey, 82% (N = 225) were included in the final analyses. Mean age at survey was 52 years, 39% were female, 85% were employed when diagnosed, 77% before HDT-ASCT and 69% at survey. Employment before HDT-ASCT corresponds with a higher probability of employment at survey for a given symptom burden. In the most extensive statistical model, it increases with 37.3 percentage points. Work hours amongst withdrawals plummet after HDT-ASCT while work ability shows a rebound effect. The potential economic gain from their re-enter into the work force equals 70% of the average annual wage in Norway in 2012. CONCLUSIONS: For a given symptom burden, staying employed throughout diagnosis and treatment is associated with a higher probability of future employment. These results favour policies for labour force inclusion past diagnosis and treatment increasing cancer survivors' probability of future employment. However, we need more research on withdrawal mechanisms, and on policy measures that promote inclusion.

Chemotherapy-induced peripheral neuropathy after modern treatment of Hodgkin's lymphoma; symptom burden and quality of life.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of Hodgkin's lymphoma (HL) treatment. We aimed to describe the prevalence of CIPN associated symptoms in long-term HL survivors compared to controls, and determine associated factors, including impact on health-related quality of life (HRQoL). MATERIAL AND METHODS: A questionnaire, including EORTC QLQ-CIPN-20 for CIPN related symptoms and SF-36 for HRQoL, was completed by 303 HL survivors at a median of 16 years after diagnosis. CIPN results were compared to a normative population (n = 606). CIPN associated factors were identified by linear regression analysis. RESULTS: Total CIPN score and subscores were significantly higher in HL survivors compared to controls. In multivariate analysis of HL survivors, a number of comorbidities (p < 0.001) and female gender (p = 0.05) were significantly associated with more CIPN. No association with disease or treatment factors was found. In a multivariate analysis including survivors and controls, the number of comorbidities (p < 0.001) and caseness (p < 0.001) were significantly associated with more CIPN. In HL survivors higher CIPN score was associated with reduced HRQoL (p < 0.001). CONCLUSION: HL survivors more than a decade after treatment report higher neuropathy-related symptom burden than controls, with a negative impact on HRQoL. Symptoms may be related to factors other than neurotoxic chemotherapy.

Using blood calprotectin as a measure of blood neutrophils.

Presently, bed-side or at home quantification of neutrophils in blood (b-neutrophils) is not practical, because cytometric methods are too expensive and technically demanding. We have explored whether calprotectin concentration in whole blood (b-calprotectin) might be a valid measure of b-neutrophils because this principle might be used in a simple and robust immunoassay device. We obtained heparin blood samples from 77 patients with possible neutropenia, most of them cancer patients treated with cytostatic drugs, and compared b-calprotectin with their b-neutrophils in a simultaneously taken EDTA-blood sample. The Spearman rank correlation coefficient between b-calprotectin and b-neutrophils was 0.986 (p < .0001). In a regression model of b-neutrophils as a function of age, gender, type of hematology instrument, total leukocyte count minus neutrophils, b-calprotectin, and plasma calprotectin (p-calprotectin), only b-calprotectin was a statistically significant predictor. B-neutrophils below 1 × 109/L was unlikely if b-calprotectin was above 50 mg/L. In conclusion, b-calprotectin, without adjusting for p-calprotectin, correlates closely with b-neutrophils and could be used to detect b-neutrophils below 1 × 109/L.

Lifestyle behavior among lymphoma survivors after high-dose therapy with autologous hematopoietic stem cell transplantation, assessed by patient-reported outcomes.

Introduction: High-dose therapy with autologous stem cell transplantation (HD-ASCT) is associated with an increased risk of late effects. Our aim was to assess lifestyle behavior and factors associated with unhealthy lifestyle among HD-ASCT-treated lymphoma survivors (HD-ASCT-LS). Materials and methods: We conducted a national cross-sectional study of HD-ASCT-LS treated during 1987-2008. Among 399 eligible participants, 312 (78%) completed patient-reported outcome measures (PROMs) on lifestyle behavior (physical activity, overweight, smoking and alcohol consumption), chronic fatigue (CF) and somatic and mental illness. We assessed lifestyle according to WHO recommendations. Multivariable logistic regression models were used to study associations between variables. A comparison to the general population was performed. Results: Mean age at survey was 54.6 years, 60% were men, 55% sedentary, 55% overweight, 18% smokers and 5% had unhealthy alcohol consumption. Being sedentary was positively associated with older age, low household income, CF and higher somatic burden (≥4 self-reported somatic conditions). Overweight was positively associated with male gender and negatively associated with increased number of chemotherapy regimens prior to HD-ASCT. Current smoking was positively associated with living alone and CF, and negatively associated with older age. Male gender, CF and higher somatic burden increased the risk of an unhealthier lifestyle whereas the increased number of chemotherapy regimens prior to HD-ASCT decreased the risk. HD-ASCT-LS were significantly less sedentary, less overweight, and had a lower likelihood of smoking than the controls. Discussion: Assessed by PROMs, unhealthy habits were frequent among HD-ASCT-LS and associated with comorbidity. Nevertheless, compared with controls significantly more HD-ASCT-LS met lifestyle recommendations. These results indicate that the HD-ASCT-LS may consist of two groups, the adhering group with less comorbidity and the non-adhering group with more comorbidity. Our findings illustrate the necessity of recommendations and support for improving health-related behavior in cancer survivorship plans in order to empower survivors in their life beyond cancer.

Survivors' knowledge of their diagnosis, treatment and possible late adverse effects after autologous stem cell transplantation for lymphoma.

Purpose: Lymphoma survivors after high dose therapy with autologous stem cell therapy (HD-ASCT) are at high risk for late adverse effects (AEs). Information patients receive and collect throughout their cancer trajectory about diagnosis, treatment schedule and risks of AEs may influence attitudes and health-related behavior in the years after treatment. The purpose of this study was to explore level of knowledge in lymphoma survivors after HD-ASCT at a median of 12 years after primary diagnosis. Material and methods: From a national study on the effects of HD-ASCT for lymphomas, 269 survivors met for an outpatient examination, including a structured interview addressing knowledge about diagnosis and treatment. Survivors were also asked whether they knew and/or had experienced certain common late AEs. Numbers of recognized and experienced late AEs were presented as sum scores. Factors associated with the level of knowledge of late AEs were analyzed by linear regression analysis. Results: Eighty-one percent of the survivors knew their diagnosis, 99% knew the components of HD-ASCT and 97% correctly recalled having had radiotherapy. Ninety percent reported awareness of late AEs, but the level of knowledge and personal experience with specified AEs varied. Thirty-five percent of survivors stated to have received follow-up for late AEs. In multivariable analysis younger age at diagnosis, having received mediastinal radiotherapy, higher mental health related quality of life, a higher number of self-experienced late AEs and having received follow-up care for late AEs were significantly associated with a higher level of knowledge of AEs. Conclusion: The majority of lymphoma survivors treated with HD-ASCT correctly recalled diagnosis and treatment, while knowledge of late AEs varied. Our findings point to information deficits in survivors at older age and with lower mental health related quality of life. They indicate benefit of follow-up to enhance education on late AEs in lymphoma survivors.

Molecular Monitoring after Autologous Stem Cell Transplantation and Preemptive Rituximab Treatment of Molecular Relapse; Results from the Nordic Mantle Cell Lymphoma Studies (MCL2 and MCL3) with Median Follow-Up of 8.5 Years.

The main objectives of the present study were to monitor minimal residual disease (MRD) in the bone marrow of patients with mantle cell lymphoma (MCL) to predict clinical relapse and guide preemptive treatment with rituximab. Among the patients enrolled in 2 prospective trials by the Nordic Lymphoma Group, 183 who had completed autologous stem cell transplantation (ASCT) and in whom an MRD marker had been obtained were included in our analysis. Fresh samples of bone marrow were analyzed for MRD by a combined standard nested and quantitative real-time PCR assay for Bcl-1/immunoglobulin heavy chain gene (IgH) and clonal IgH rearrangements. Significantly shorter progression-free survival (PFS) and overall survival (OS) was demonstrated for patients who were MRD positive pre-ASCT (54 patients) or in the first analysis post-ASCT (23 patients). The median PFS was only 20 months in those who were MRD-positive in the first sample post-ASCT, compared with 142 months in the MRD-negative group (P < .0001). OS was 75% at 10 years and median not reached in the MRD-negative group, compared with only 35 months in the MRD-positive group (P < .0001). Of the 86 patients (47%) who remained in continuous molecular remission, 73% were still in clinical remission after 10 years. For all patients, the median time from ASCT to first molecular relapse was 55 months, with a continuous occurrence of late molecular relapses. Fifty-eight patients who experienced MRD relapse received rituximab as preemptive treatment on 1 or more occasions, and in this group, the median time from first molecular relapse to clinical relapse was 55 months. In most cases, rituximab converted patients to MRD negativity (87%), but many patients became MRD-positive again later during follow-up (69%). By multivariate analysis, high-risk Mantle Cell Lymphoma International Prognostic Index score and positive MRD status pre-ASCT predicted early molecular relapse. In conclusion, preemptive rituximab treatment converts patients to MRD negativity and likely postpones clinical relapse. Molecular monitoring offers an opportunity to select some patients for therapeutic intervention and to avoid unnecessary treatment in others. MRD-positive patients in the first analysis post-ASCT have a dismal prognosis and thus are in need of novel strategies.

A national study on conditional survival, excess mortality and second cancer after high dose therapy with autologous stem cell transplantation for non-Hodgkin lymphoma.

This national population-based study aimed to investigate conditional survival and standardized mortality ratios (SMR) after high-dose therapy with autologous stem-cell transplantation (HDT-ASCT) for non-Hodgkin lymphoma (NHL), and to analyse cause of death, relapses and second malignancies. All patients ≥18 years treated with HDT-ASCT for NHL in Norway between 1987 and 2008 were included (n = 578). Information from the Cause of Death Registry and Cancer Registry of Norway were linked with clinical data. The 5-, 10- and 20-year overall survival was 61% (95% confidence interval [CI] 56-64%), 52% (95%CI 48-56%) and 45% (95%CI 40-50%), respectively. The 5-year survival conditional on having survived 2, 5 and 10 years after HDT-ASCT was 81%, 86% and 93%. SMRs were 12·3 (95%CI 11·0-13·9), 4·9 (95%CI 4·1-5·9), 2·4 (95%CI 1·8-3·2) and 1·0 (95%CI 0·6-1·8) for the entire cohort and for patients having survived 2, 5 and 10 years after HDT-ASCT respectively. Of the 281 deaths observed, 77% were relapse-related. Treatment-related mortality was 3·6%. The 10-year cumulative incidence of second malignancies was 7·9% and standardized incidence ratio was 2·0 (95%CI 1·5-2·6). NHL patients treated with HDT-ASCT were at increased risk of second cancer and premature death. The mortality was still elevated at 5 years, but after 10 years mortality equalled that of the general population.

Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma.

The main objective of the MCL3 study was to improve outcome for patients not in complete remission (CR) before transplant by adding (90)Y-ibritumomab-tiuxetan (Zevalin) to the high-dose regimen. One hundred sixty untreated, stage II-IV mantle cell lymphoma patients <66 years received rituximab (R)-maxi-CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) alternating with R-high-dose cytarabine (6 cycles total), followed by high-dose BEAM/C (bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan or cyclophosphamide) and autologous stem cell transplantation from 2005 to 2009. Zevalin (0.4 mCi/kg) was given to responders not in CR before transplant. Overall response rate pretransplant was 97%. The outcome did not differ from that of the historic control: the MCL2 trial with similar treatment except for Zevalin. Overall survival (OS), event-free survival (EFS), and progression-free survival (PFS) at 4 years were 78%, 62%, and 71%, respectively. For responding non-CR patients who received Zevalin, duration of response was shorter than for the CR group. Inferior PFS, EFS, and OS were predicted by positron emission tomography (PET) positivity pretransplant and detectable minimal residual disease (MRD) after transplant. In conclusion, positive PET and MRD were strong predictors of outcome. Intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant. This trial was registered at www.clinicaltrials.gov as #NCT00514475.

Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by the Nordic Lymphoma Group.

The Nordic Lymphoma Group has conducted a phase ll trial in newly diagnosed primary central nervous system lymphoma patients applying an age-adjusted multi-agent immunochemotherapy regimen, which in elderly patients included temozolomide maintenance treatment. Patients aged 18-75 years were eligible. Thirty-nine patients aged 18-65 years and 27 patients aged 66-75 years were enrolled. The median age of the two age groups was 55 and 70 years, respectively. The overall response rate was 73.8% for the entire cohort: 69.9% in the younger and 80.8% in the elderly subgroup. With a median follow up of 22 months, the 2-year overall survival probability was 60.7% in patients aged 65 years or under and 55.6% in patients aged over 65 years (P=0.40). The estimated progression-free survival at two years was 33.1% (95%CI: 19.1%-47.9%) in patients aged under 65 years and 44.4% (95%CI: 25.6%-61.8%) in the elderly subgroup (P=0.74). Median duration of response was ten months in the younger subgroup, and not reached in the elderly patient subgroup (P=0.33). Four patients aged 64-75 years (6%) died from treatment-related complications. Survival in the two age groups was similar despite a de-escalation of induction treatment in patients aged over 65 years. Duration of response in elderly patients receiving maintenance temozolomide was longer than in the younger age subgroup. While toxicity during induction is still of concern, especially in the elderly patients, we conclude from these data that de-escalation of induction therapy in elderly primary central nervous system lymphoma patients followed by maintenance treatment seems to be a promising treatment strategy. (clinicaltrials.gov identifier:01458730).

PET/MR brain imaging: evaluation of clinical UTE-based attenuation correction.

UNLABELLED: One of the greatest challenges in PET/MR imaging is that of accurate MR-based attenuation correction (AC) of the acquired PET data, which must be solved if the PET/MR modality is to reach its full potential. The aim of this study was to investigate the performance of Siemens' most recent version (VB20P) of MR-based AC of head PET data, by comparing it to CT-based AC. METHODS: (18)F-FDG PET data from seven lymphoma and twelve lung cancer patients examined with a Biograph mMR PET/MR system were reconstructed with both CT-based and MR-based AC, avoiding sources of error arising when comparing PET data from different systems. The resulting images were compared quantitatively by measuring changes in mean SUV in ten different brain regions in both hemispheres, as well as the brainstem. In addition, the attenuation maps (µ maps) were compared regarding volume and localization of cranial bone. RESULTS: The UTE µ maps clearly overestimate the amount of bone in the neck, while slightly underestimating the amount of bone in the cranium, and the localization of bone in the cranial region also differ from the CT µ maps. In air/tissue interfaces in the sinuses and ears, the MRAC method struggles to correctly classify the different tissues. The misclassification of tissue is most likely caused by a combination of artefacts and the insufficiency of the UTE method to accurately separate bone. Quantitatively, this results in a combination of overestimation (0.5-3.6 %) and underestimation (2.7-5.2 %) of PET activity throughout the brain, depending on the proximity to the inaccurate regions. CONCLUSIONS: Our results indicate that the performance of the UTE method as implemented in VB20P is close to the theoretical maximum of such an MRAC method in the brain, while it does not perform satisfactorily in the neck or face/nasal area. Further improvement of the UTE MRAC or other available methods for more accurate segmentation of bone should be incorporated.

18F-FACBC and 18F-FDG PET/MRI in the evaluation of 3 patients with primary central nervous system lymphoma: a pilot study.

BACKGROUND: This PET/MRI study compared contrast-enhanced MRI, 18F-FACBC-, and 18F-FDG-PET in the detection of primary central nervous system lymphomas (PCNSL) in patients before and after high-dose methotrexate chemotherapy. Three immunocompetent PCNSL patients with diffuse large B-cell lymphoma received dynamic 18F-FACBC- and 18F-FDG-PET/MRI at baseline and response assessment. Lesion detection was defined by clinical evaluation of contrast enhanced T1 MRI (ce-MRI) and visual PET tracer uptake. SUVs and tumor-to-background ratios (TBRs) (for 18F-FACBC and 18F-FDG) and time-activity curves (for 18F-FACBC) were assessed. RESULTS: At baseline, seven ce-MRI detected lesions were also detected with 18F-FACBC with high SUVs and TBRs (SUVmax:mean, 4.73, TBRmax: mean, 9.32, SUVpeak: mean, 3.21, TBRpeak:mean: 6.30). High TBR values of 18F-FACBC detected lesions were attributed to low SUVbackground. Baseline 18F-FDG detected six lesions with high SUVs (SUVmax: mean, 13.88). In response scans, two lesions were detected with ce-MRI, while only one was detected with 18F-FACBC. The lesion not detected with 18F-FACBC was a small atypical MRI detected lesion, which may indicate no residual disease, as this patient was still in complete remission 12 months after initial diagnosis. No lesions were detected with 18F-FDG in the response scans. CONCLUSIONS: 18F-FACBC provided high tumor contrast, outperforming 18F-FDG in lesion detection at both baseline and in response assessment. 18F-FACBC may be a useful supplement to ce-MRI in PCNSL detection and response assessment, but further studies are required to validate these findings. Trial registration ClinicalTrials.gov. Registered 15th of June 2017 (Identifier: NCT03188354, https://clinicaltrials.gov/study/NCT03188354 ).

High-dose therapy with autologous stem cell support for lymphoma in Norway 1987-2008.

BACKGROUND: High-dose therapy with autologous stem cell support (HDT) has been a treatment option for lymphomas in Norway for 25 years. The purpose of the article was to describe the use of the therapy for lymphomas for the country as a whole and by health region, and to reveal the overall survival rate. METHOD: All lymphoma patients ≥ 18 years who received HDT in Norway in the period 1987-2008 are included. Patients, diagnostics and treatment are identified for each hospital. Data for the population base have been retrieved from Statistics Norway. RESULTS: Altogether 726 lymphoma patients received HDT in Norway in the period 1987-2008, with an annual average of 0.72 per 100,000 inhabitants. The annual number of treatments increased until 2004 and has since been stable. The average number of treatments per 100,000 inhabitants per year was 0.94 for Northern Norway Health Region, 0.80 for South-Eastern Norway Health Region, 0.58 for Central Norway Health Region and 0.55 for Western Norway Health Region. Early mortality (death within 100 days) was 6%. Ten-year overall survival was 55% (95% CI 51-59%), and Hodgkin's lymphoma had the best survival of the lymphoma groups (p = 0.01). INTERPRETATION: The annual number of HDT increased gradually until 2004. The use of the treatment varied according to the patients' place of residence at the time of diagnosis, and was most frequently used for patients belonging to Northern Norway Health Region. More than half of the lymphoma patients are alive ten years after the treatment.