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.

Factors influencing access to palliative radiotherapy: a Norwegian population-based study.

BACKGROUND: Palliative radiotherapy (PRT) comprises half of all radiotherapy use and is an effective and important treatment modality for improving quality of life in incurable cancer patients. We have described the use of PRT in Norway and aimed to identify and quantify the impact of factors associated with PRT utilization. MATERIAL AND METHODS: Population-based data from the Cancer Registry of Norway identified 25,281 patients who died of cancer, 1 July 2009-31 December 2011. Additionally, individual-level data on socioeconomic status and community-level data on travel distance were collected. The proportion of patients who received PRT in the last two years of life (PRT2Y) was calculated, and multivariable logistic regression was used to determine factors that influenced the PRT2Y. Analyses of geographic variation in PRT use were also performed for the time period 2012-2016. RESULTS: PRT2Y for all cancer sites combined was 29.6% with wide geographic variations (standardized inter-county range; 21.8-36.6%). Female gender, increasing age at death, certain cancer sites, short survival time, and previous receipt of curative radiotherapy were associated with decreased odds of receiving PRT. Patients with low education, those living in certain counties, or with travel distances 100-499 km, were also less likely to receive PRT. Patients with low household income (adjusted odds ratio (OR) = 0.63; 95% confidence interval (CI) = 0.56-0.72) and those diagnosed in hospitals without radiotherapy facility (OR = 0.70; 95% CI = 0.64-0.77) had especially low likelihood of receiving PRT. Significant inter-county variation in use of PRT remained during the time period 2012-2016. CONCLUSIONS: Despite a publicly funded, universal healthcare system with equity as a stated health policy aim, utilization of PRT in Norway is significantly associated with factors such as household income and availability of radiotherapy facility at the diagnosing hospital. Even after adjustments for relevant factors, unexplained geographic variations in PRT utilization exist.

Obstructive and restrictive pulmonary dysfunction in long-term lymphoma survivors after high-dose therapy with autologous stem cell transplantation.

BACKGROUND: Obstructive and restrictive dysfunction in long-term lymphoma survivors (LSs) after high-dose therapy with autologous stem-cell transplantation (HDT-ASCT) has not been addressed systematically previously. MATERIAL AND METHODS: LSs treated in Norway 1987-2008 with HDT-ASCT who performed spirometry, measurement of static lung volumes and echocardiography 2012-2014 at either Oslo or St. Olavs University Hospitals was eligible. Smoking data were recorded by questionnaire. Treatment data were collected from medical records or hospital databases. Factors associated with obstructive and restrictive impairments (dichotomous outcomes) were examined by Poisson regression. Linear regression with the margins post-estimation command was used to derive adjusted mean values of forced expiratory volume in 1 s (FEV1). We used the normative reference data recommended by the European Respiratory Society for calculating percent predicted values. RESULTS: A total of 226 LSs were studied, of whom 11.5 and 5.8% had obstructive and restrictive impairment, respectively. For women and men, mean FEV1 was 2.31 and 3.34 l corresponding to 11.4%- and 11.1%-points below that predicted from norms, respectively. In multivariable regression analyses, cumulative doxorubicin dose (400-775 mg/m2) and current smoking were associated with increased risk of obstructive impairment, and chest RT (>13-66 Gy) was associated with increased risk of restrictive impairment. Currently smoking LSs within the highest doxorubicin category (400-775 mg/m2), had the lowest adjusted mean FEV1. CONCLUSIONS: Despite intensive cancer treatment, our analysis showed modest reductions in obstructive parameters among long-term LSs after HDT-ASCT compared to normative reference data. To limit obstructive impairments in LSs after HDT-ASCT, we suggest that targeted smoking-cessation advice is directed towards patients who have received high cumulative doses of doxorubicin.

Cardiorespiratory fitness in long-term lymphoma survivors after high-dose chemotherapy with autologous stem cell transplantation.

BACKGROUND: Cardiorespiratory fitness as measured by peak oxygen consumption (VO2peak) is a strong predictor of longevity and may be compromised by anticancer therapy, inactivity, and smoking. We compared VO2peak among lymphoma survivors (LSs) with reference data from healthy sedentary subjects, after a 10.2-year (mean) follow-up post high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT). We further examined the association between VO2peak and treatment, physical activity, smoking, pulmonary, and cardiac function. METHODS: Lymphoma survivors treated with HDT-ASCT in Norway 1987-2008 were eligible. VO2peak was assessed by cardiopulmonary exercise testing. Pulmonary function testing and echocardiography were also conducted. Data on treatment, physical activity, and smoking were collected from hospital records and questionnaires. VO2peak was compared with age-sex predicted reference data. Linear regression was used to associate clinical factors with VO2peak cross-sectionally. RESULTS: A total of 194 LSs without heart failure were studied. Mean VO2peak was 4.5% and 7.7% below norms in females and males, respectively. Twenty-two percent had impaired (<80% predicted) VO2peak. Decreasing VO2peak was associated with impaired diffusion capacity and current smoking, while physical activity level and VO2peak were positively associated. CONCLUSION: We suggest increased attention towards physical activity counseling and smoking cessation advice to preserve cardiorespiratory fitness in LSs after HDT-ASCT. Patients with impaired diffusion capacity may benefit from subsequent monitoring to detect pulmonary vascular diseases.

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.

Heart Failure and Asymptomatic Left Ventricular Systolic Dysfunction in Lymphoma Survivors Treated With Autologous Stem-Cell Transplantation: A National Cross-Sectional Study.

PURPOSE: We aimed to determine the prevalence of left ventricular systolic dysfunction (LVSD), including symptomatic (ie, heart failure [HF]) and asymptomatic LVSD in adult lymphoma survivors (LSs) after autologous hematopoietic stem-cell transplantation (auto-HCT) and to identify risk factors for LVSD in this population. PATIENTS AND METHODS: All LSs treated with auto-HCT as adults in Norway from 1987 to 2008 were eligible for this national cross-sectional study. Asymptomatic LVSD was defined as left ventricular ejection fraction less than 50% by echocardiography, and HF was defined according to current recommendations. The results in LSs were compared with those found in an age- and sex-matched (1:1) control group. RESULTS: We examined 274 LSs (69% of all eligible survivors); 62% were men, the mean (± standard deviation) age was 56 ± 12 years, and mean follow-up time from lymphoma diagnosis was 13 ± 6 years. The mean cumulative doxorubicin dose was 316 ± 111 mg/m(2), and 35% of LSs had received additional radiation therapy involving the heart. We found LVSD in 15.7% of the LSs, of whom 5.1% were asymptomatic. HF patients were symptomatically mildly affected, with 8.8% of all LSs classified as New York Heart Association class II, whereas more severe HF was rare (1.8%). Compared with controls, LSs had a substantially increased LVSD risk (odds ratio, 6.6; 95% CI, 2.5 to 17.6; P < .001). A doxorubicin dose ≥ 300 mg/m(2) and cardiac radiation therapy dose greater than 30 Gy were independent risk factors for LVSD. CONCLUSION: LVSD was frequent and HF more prevalent than previously reported in LSs after auto-HCT. Our results may help to identify LSs at increased LVSD risk and can serve as a basis for targeted surveillance strategies.

Utilization of radiation therapy in Norway after the implementation of the national cancer plan--a national, population-based study.

PURPOSE: To estimate actual utilization rates of radiation therapy (RT) in Norway, describe time trends (1997-2010), and compare these estimates with corresponding optimal RT rates. METHODS AND MATERIALS: Data from the population-based Cancer Registry of Norway was used to identify all patients diagnosed with cancer and/or treated by RT for cancer in 1997-2010. Radiation therapy utilization rates (RURs) were calculated as (1) the proportion of incident cancer cases who received RT at least once within 1 year of diagnosis (RUR1Y); and (2) the proportion who received RT within 5 years of diagnosis (RUR5Y). The number of RT treatment courses per incident cancer case (TCI) was also calculated for all cancer sites combined. The actual RURs were compared with corresponding Australian and Canadian epidemiologic- and evidence-based model estimates and criterion-based benchmark estimates of optimal RURs. The TCIs were compared with TCI estimates from the 1997 Norwegian/National Cancer Plan (NCP). Joinpoint regression was used to identify changes in trends and to estimate annual percentage change (APC) in actual RUR1Y and actual TCI. RESULTS: The actual RUR5Y (all sites) increased significantly to 29% in 2005 but still differed markedly from the Australian epidemiologic- and evidence-based model estimate of 48%. With the exception of RUR5Y for breast cancer and RUR1Y for lung cancers, all actual RURs were markedly lower than optimal RUR estimates. The actual TCI increased significantly during the study period, reaching 42.5% in 2010, but was still lower than the 54% recommended in the NCP. The trend for RUR1Y (all sites) and TCI changed significantly, with the annual percentage change being largest during the first part of the study period. CONCLUSIONS: Utilization rates of RT in Norway increased after the NCP was implemented and RT capacity was increased, but they still seem to be lower than optimal levels.

Atherosclerotic lesions in lymphoma survivors treated with radiotherapy.

BACKGROUND AND PURPOSE: Radiotherapy causes premature atherosclerosis in Hodgkin's lymphoma survivors (HLSs). We determined whether atherosclerosis within the radiation field was predicted by traditional risk factors independent of radiation and compared the extent of atherosclerosis in HLSs treated with mantle field radiotherapy with non-irradiated patients. MATERIAL AND METHODS: Forty-three HLSs (median age 50 years, range 38-63) treated with mantle field radiotherapy were included. Cardiovascular risk factors were registered at first follow-up (FU-1) 5-13 years after treatment. A second follow-up (FU-2) occurred 18-27 years after treatment. At FU-2, in-field atherosclerosis was assessed by computed tomography with calculation of coronary artery calcium volume score (CACS) and pre-cranial artery atherosclerosis score (PAS). Peripheral endothelial dysfunction was assessed by ante-brachial strain-gauge plethysmography. CT angiography of pre-cranial vessels was also performed in 43 non-irradiated patients. RESULTS: Multiple linear regression analyses showed that cholesterol at FU-1 was a predictor of CACS (ß 308 (95% CI 213-403), p < 0.001), PAS (ß 3.67 (95% CI 2.29-5.04), p < 0.001) and peripheral endothelial dysfunction (ß 2.74 (95% CI 0.47-5.01), p = 0.02). There were more atherosclerotic lesions in HLSs (n = 141) than in non-irradiated patients (n = 73, p = 0.001). CONCLUSION: Irradiated arteries are characterized by widespread atherosclerotic lesions aggravated by elevated levels of cholesterol.

Multimodal treatment with ALL-like chemotherapy, Auto-SCT and radiotherapy for lymphoblastic lymphoma.

BACKGROUND: Recommended treatment for lymphoblastic lymphomas, a highly aggressive, relatively rare lymphoma entity predominantly seen in teenagers and young adults, includes acute lymphoblastic leukemia (ALL)-like induction chemotherapy. Whether these patients should be consolidated with maintenance chemotherapy or autologous stem cell transplantation (Auto-SCT) and the use of radiotherapy are matters of debate. METHODS: We reviewed treatment and outcome for 25 consecutive patients above the age of 15 years with lymphoblastic lymphoma (T-lineage; T-LBL, n = 19; B-lineage; B-LBL, n = 6) seen at a single center during a 12-year period (1999-2011). Patients were given an ALL-like chemotherapy induction regimen, and responding patients were consolidated with Auto-SCT and local radiotherapy when applicable. RESULTS: Median age at diagnosis was 33 years (range 15-65). Seventeen of the T-LBL patients had a mediastinal mass, three patients had central nervous system (CNS) involvement. Chemotherapy with intensified CNS prophylaxis induced an overall response rate of 92% (CR 84%, PR 8%). In total 23/25 (92%) patients underwent Auto-SCT in first remission while 13 of 14 eligible patients with mediastinal involvement received local radiotherapy. Twenty percent of the patients had hepatotoxicity grade 3-4 and 32% thromboembolic events (TE). Two patients (8%) died of treatment-related toxicity. One patient had progressive disease and died of lymphoma. Three patients have relapsed, but two of these (both B-LBL) are currently alive in second CR after Allo-SCT. With a median follow-up of 98 months (range 1-163) the 5- and 8-year PFS and OS are 76% and 84%, respectively. CONCLUSIONS: Combined intensive ALL-like induction and early consolidation chemotherapy followed by Auto-SCT and local radiation therapy resulted in high sustained cure rates.

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.

High-dose therapy with autologous stem cell support for lymphoma--from experimental to standard treatment.

High-dose therapy with autologous stem cell support (HDT) has been a therapeutic option for lymphomas in Norway since as far back as 1987. By restoring bone marrow function through reinfusion of the patient's own stem cells, it is possible to administer cancer treatment in higher and otherwise lethal doses, and thereby achieve better treatment results. Originally stem cells were harvested from bone marrow and the high-dose therapy included total body irradiation, but since the mid 1990s stem cells have been harvested by apheresis and the high-dose therapy has consisted of chemotherapy alone (BEAM chemotherapy). In 1995 the treatment was regionalised and since then it has been performed in all health regions. The HDT procedure was introduced as an experimental treatment in clinical studies with international collaboration. The indications have changed over time, and this is now established treatment for a number of types of lymphoma.

The Norwegian experience with penicillin G plus an aminoglycoside as initial empiric therapy in febrile neutropenia; a review.

BACKGROUND: The occurrence of antibiotic resistance and the use of broad-spectrum antibiotics are relatively low in Norway. The national recommendation in febrile neutropenia (FN) is prompt initial therapy with penicillin G plus an aminoglycoside. We sought to evaluate the evidence behind this recommendation. METHODS: We did a literature search in Medline and EMBASE with search terms penicillin, aminoglycoside and febrile neutropenia. RESULTS: Seven Norwegian studies (six adult and one pediatric) conducted over the last 25 years were identified. They all conclude that penicillin G plus an aminoglycoside are effective and safe initial empiric antibiotic therapy in FN provided the regimen is modified if the clinical response is unsatisfactory. Overall 40-50% of the patients required only penicillin G and an aminoglycoside during their FN episode. The overall fatality rate was similar in the Norwegian and in international studies. CONCLUSION: Many countries use a broad-spectrum ß-lactam as initial therapy in FN. International experts are sceptic towards the Norwegian recommendations. We discuss the arguments for and against penicillin G plus an aminoglycoside in FN. The main arguments to continue the Norwegian treatment tradition are the satisfactory clinical results and the reason to believe that it contributes to the low levels of antibiotic resistance in Norway.

CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group.

BACKGROUND: The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen in young patients with good-prognosis diffuse large-B-cell lymphoma. Extended follow-up was needed to establish long-term effects. METHODS: In the randomised open-label MInT study, patients from 18 countries (aged 18-60 years with none or one risk factor according to the age-adjusted International Prognostic Index [IPI], stage II-IV disease or stage I disease with bulk) were randomly assigned to receive six cycles of a CHOP-like chemotherapy with or without rituximab. Bulky and extranodal sites received additional radiotherapy. Randomisation was done centrally with a computer-based tool and was stratified by centre, bulky disease, age-adjusted IPI, and chemotherapy regimen by use of a modified minimisation algorithm that incorporated a stochastic component. Patients and investigators were not masked to treatment allocation. The primary endpoint was event-free survival. Analyses were by intention to treat. This observational study is a follow-up of the MInT trial, which was stopped in 2003, and is registered at ClinicalTrials.gov, number NCT00400907. FINDINGS: The intention-to-treat population included 410 patients assigned to chemotherapy alone and 413 assigned to chemotherapy plus rituximab. After a median follow-up of 72 months (range 0·03-119), 6-year event-free survival was 55·8% (95% CI 50·4-60·9; 166 events) for patients assigned to chemotherapy alone and 74·3% (69·3-78·6; 98 events) for those assigned to chemotherapy plus rituximab (difference between groups 18·5%, 11·5-25·4, log-rank p<0·0001). Multivariable analyses showed that event-free survival was affected by treatment group, presence of bulky disease, and age-adjusted IPI and that overall survival was affected by treatment group and presence of bulky disease only. After chemotherapy and rituximab, a favourable subgroup (IPI=0, no bulk) could be defined from a less favourable subgroup (IPI=1 or bulk, or both; event-free survival 84·3% [95% CI 74·2-90·7] vs 71·0% [65·1-76·1], log-rank p=0·005). 18 (4·4%, 95% CI 2·6-6·9) second malignancies occurred in the chemotherapy-alone group and 16 (3·9%, 2·2-6·2) in the chemotherapy and rituximab group (Fisher's exact p=0·730). INTERPRETATION: Rituximab added to six cycles of CHOP-like chemotherapy improved long-term outcomes for young patients with good-prognosis diffuse large-B-cell lymphoma. The definition of two prognostic subgroups allows a more refined therapeutic approach to these patients than does assessment by IPI alone. FUNDING: Hoffmann-La Roche.

Effects of a computer-supported interactive tailored patient assessment tool on patient care, symptom distress, and patients' need for symptom management support: a randomized clinical trial.

OBJECTIVE: To examine the effects of a computer-assisted, interactive tailored patient assessment (ITPA) tool in oncology practice on: documented patient care, symptom distress, and patients' need for symptom management support during treatment and rehabilitation. DESIGN AND METHODS: For this repeated measures clinical trial at a university hospital in Norway, 145 patients starting treatment for leukemia or lymphoma were randomly assigned to either an intervention (n=75) or control group (n=70). Both groups used the ITPA for symptom assessments prior to inpatient and outpatient visits for up to one year. The assessment summary, which displayed patients' self-reported symptoms, problems, and distress in rank-order of the patient's need for support, was provided to physicians and nurses in the intervention group only but not in the control group. RESULTS: Significantly more symptoms were addressed in the intervention group patient charts versus those of the control group. Symptom distress in the intervention group decreased significantly over time in 11 (58%) of 19 symptom/problem categories versus 2 (10%) for the control group. Need for symptom management support over time also decreased significantly more for the intervention group than the control group in 13 (68%) symptom categories. CONCLUSION: This is the first study to show that an ITPA used in an interdisciplinary oncology practice can significantly improve patient-centered care and patient outcomes, including reduced symptom distress and reduced need for symptom management support.

[Use of radiotherapy in South-Eastern Norway Regional Health Authority]. / Bruk av stråleterapi i Helse Sør-Øst.

BACKGROUND: The National Cancer Plan (NCP) provided the incentives needed to establish a technical infrastructure adequate to meet the medical needs of radiotherapy in cancer care. The goal of this study is to evaluate the development of radiotherapy in South-Eastern Norway Regional Health Authority (S-E NRHA) and to compare it with the aims of NCP. MATERIAL AND METHODS: The material includes the 86,000 courses of radiotherapy performed in S-E NRHA in the period 1985-2008. The data were extracted from existing patient registries and include cancer diagnosis and patient demographic information. The number of treatment series is coupled with cancer incidence of each county and that in S-E NRHA. RESULTS: During the latter half of the 1980s, radiotherapy was only offered to 50 % (range 30-60 % in the various counties) of those who needed it. The situation had improved in 2007, when this figure was close to 80 %, but there was still a significant discrepancy between counties (67-91 %). With respect to the medical needs, 10 000 additional courses of radiotherapy should have been performed in S-E NRHA in the period 2003-2007. INTERPRETATION: The demonstrated insufficient use of radiotherapy and the geographical differences between counties are not acceptable. A prerequisite for optimal use of radiotherapy in cancer treatment is that the medical professions strengthen their oncological competence.

[Molecular diagnosis of malignant lymphomas]. / Molekylaer diagnostikk av maligne lymfomer.

BACKGROUND: Malignant lymphomas comprise a heterogeneous group of non-solid tumors originating in lymphocytes at different maturation stages. The diagnosis is based on a traditional histopathological diagnostic procedure supplemented with immunophenotyping, cytogenetics, molecular genetic analyses and clinical information. This article describes experimental molecular diagnostics, mainly based on microarray-based gene expression technology. MATERIAL AND METHODS: Results achieved through an international multicentre project (headed by the National Cancer Institute in the USA), in which the Norwegian Radium Hospital has taken part as the only Nordic institution, are summarized. The findings are discussed in light of other relevant studies identified through a non-systematic search in PubMed. RESULTS: New clinically relevant subgroups of malignant B-cell lymphomas have been characterized. Retrospective survival analyses have shown correlations between gene expression profiles and patient outcome and have provided important biological knowledge, which has led to new targeted treatments (currently being tested in clinical studies). INTERPRETATION: As a supplement to today's diagnostics, molecular diagnostics yields an improved diagnostic precision and opens up for new treatment possibilities for patients with malignant lymphomas.

[Penicillin and aminoglycoside in febrile neutropenia]. / Penicillin og aminoglykosid ved febril nøytropeni.

BACKGROUND: Fever in patients with neutropenia may indicate a serious/lethal underlying bacterial sepsis. In Norway, penicillin G in combination with an aminoglycoside is the therapy of choice for this indication. In most countries, empiric monotherapy starts with a broadspectrum betalactam antibiotic. MATERIAL AND METHODS: Review of the literature and expert opinion identified five Norwegian studies evaluating therapy with penicillin in combination with an aminoglycoside in febrile neutropenia. These studies are presented and assessed. RESULTS: Mortality in febrile neutropenia is approximately 5 % both in the Norwegian studies and in larger international trials. Therapy which starts with penicillin and an aminoglycoside needs to be modified more frequently(60 %) than when it starts with broadspectrum betalactam monotherapy (40 %). The Norwegian studies span 20 years. Clinical blood culture isolates from this group of patients show stable resistance patterns. INTERPRETATION: In spite of methodological weaknesses, all the studies have the same conclusion: penicillin G in combination with an aminoglycoside is an effective and safe initial empiric therapy provided it is modified when the clinical course is unsatisfactory.

[Courses for cancer patients--15 years' experience at The Montebello Centre in Norway]. / Kurs for kreftrammede--15 års erfaringer fra Montebello-senteret.

BACKGROUND: The Montebello Centre offers cancer patients and their relatives courses of 5-10 days duration aimed at improving their coping with their disease. MATERIAL AND METHODS: Data on all patients admitted to the Centre 1991-2004 were linked with data from the Norwegian Cancer Registry (n = 10,173). Patients and relatives who took courses in 2004 or 2005 were asked to fill in questionnaires concerning usefulness and satisfaction with the courses. RESULTS: Patients from all parts of Norway have signed up for the courses without substantial regional differences. In relation to the incidence of cancer, most patients came from northern Norway. Women with breast cancer constituted the largest group of patients. One third of the patients were men, and that proportion increased throughout the observation period. Most patients were admitted less than two years after their initial diagnosis. After the year 2000, 67% of the patients have been accompanied by someone. Starting with the first course the five year survival rates were 69% for females and 52% for males. More than 90% of patients and relatives stated that the courses had improved their knowledge of cancer, their coping skills and given new social contacts. INTERPRETATION: The Montebello Centre functions as a national centre. Men and accompanying persons are admitted in an increasing proportion. At the end of the course both patients and their relatives reported the courses to be highly useful, and displayed a high degree of satisfaction . There is a need to know more about the long-term effects of the courses.

Prognostic significance of maximum tumour (bulk) diameter in young patients with good-prognosis diffuse large-B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: an exploratory analysis of the MabThera International Trial Group (MInT) study.

BACKGROUND: The definition and role of bulky disease in young patients (ie, aged 18-60 years) with good-prognosis diffuse large-B-cell lymphoma (DLBCL), who have been treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-like chemotherapy with or without rituximab, remain controversial. We aimed to assess the effect of maximum tumour diameter (MTD) in these patients. METHODS: Patients from the MInT (Mabthera International Trial Group) study were eligible. We analysed event-free (EFS) and overall survival (OS) after CHOP-like chemotherapy with or without rituximab, according to MTD, by Martingale residual analyses and Cox regression models. Radiotherapy was given to sites of primary bulky disease according to national standards, and to primary extranodal disease at physician discretion. The primary endpoint was EFS and the secondary endpoint was OS. Analyses were by intention to treat. FINDINGS: Of the 824 patients enrolled in the MInT study, the informed-consent form of one patient was missing, leaving 823 patients evaluable for intention-to-treat analysis. Data on MTD of involved sites were available for 802 patients. Martingale residual analysis showed an adverse prognostic effect of MTD on EFS and OS, which increased linearly. In a multivariable analysis with MTD as a linear regression variable, the effect of MTD was significant after CHOP-like treatment alone for EFS (hazard ratio 1.090 [95% CI 1.051-1.130], p < 0.0001) and OS (1.119 [1.057-1.184], p = 0.0001), and after CHOP-like treatment and rituximab for OS (1.089 [1.003-1.183], p = 0.043), but not for EFS (1.044 [0.991-1.099], p=0.103). For CHOP-like treatment alone, 3-year EFS ranged from 78.2% (MTD < 5.0 cm, 95% CI 68.3-85.4) to 41.3% (MTD > or = 10.0 cm, 31.8-50.4). For CHOP-like treatment and rituximab, 3-year EFS ranged from 83.2% (MTD < 5.0 cm, 72.8-89.9) to 72.7% (MTD > or = 10.0 cm, 63.8-79.7). With CHOP-like treatment alone, 3-year OS decreased from 92.9% (MTD < 5.0 cm, 84.9-96.8) to 73.5% (MTD > or = 10.0 cm, 63.9-81.0); for CHOP-like treatment and rituximab, 3-year OS decreased from 98.0% (MTD < 5.0 cm, 92.2-99.5) to 85.2% (MTD > or = 10.0 cm, 77.0-90.6). For CHOP-like treatment, any cut-off point between 5.0 cm and 10.0 cm separated two populations with a significant EFS difference (p < 0.0001 for all log-rank tests) and OS difference (p < or = 0.003 for all log-rank tests). For CHOP-like treatment and rituximab, only a cut-off point of 10.0 cm separated two populations with a significant EFS difference (log-rank p = 0.047), but any cut-off point of 6.0 cm or more separated two populations with a significant OS difference (log-rank p values 0.0009-0.037). INTERPRETATION: Rituximab decreased, but did not eliminate the adverse prognostic effect of MTD in young patients with good-prognosis DLBCL. Due to the linear prognostic effect of MTD on outcome, arbitrary cut-off points for bulky disease can be set between 5.0 cm and 10.0 cm, depending on clinical considerations. Based on this study, a cut-off point of 10.0 cm might be a suitable margin in the rituximab era to delineate those patients with bulky disease.