Background: To determine the incidence and risk factors for central nervous system (CNS) relapse in patients with non-Hodgkin’s lymphoma (NHL). Patients and methods: Patient records were registered ...prospectively in successive patients with NHL admitted to the Norwegian Radium Hospital from 1980 to 1996. A total of 2514 patients had no CNS involvement at diagnosis and were treated according to standard protocols. The incidence and risk factors for CNS progression or relapse were examined retrospectively. Results: In low-grade (L)-NHL, the risk of CNS involvement was low (2.8%). In high-grade (H)-NHL, lymphoblastic and Burkitt’s NHL patients had a high risk of CNS recurrence (24.4%) at 5 years, and prophylaxis seemed to reduce this risk. For the other patients with H-NHL, the proportion with CNS involvement at 5 years was 5.2%. Multivariate analysis identified five independent risk factors, each present in >5% of patients: elevated serum lactate dehydrogenase, serum albumin <35 g/l, <60 years of age, retroperitoneal lymph node involvement and involvement of more than one extranodal site. If four or five of these risk factors were present, the risk of CNS recurrence was in excess of 25% at 5 years. Conclusions: The risk of CNS involvement in this study is comparable with the results from other large series. CNS prophylaxis is not recommended in any subgroup of L-NHL. The risk of CNS involvement among patients with either Burkitt’s or lymphoblastic lymphomas is considerable and these patients should therefore receive intensive chemotherapy including systemic and intrathecal methotrexate. Patients with other types of H-NHL should receive adequate CNS prophylaxis if at least four of the five risk factors identified are present.
Background This study examined employment patterns and associated factors in lymphoma survivors treated with high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT) from diagnosis ...to a follow-up survey at a mean of 10 years after HDT-ASCT. Patients and methods All lymphoma survivors aged ≥18 years at HDT-ASCT in Norway from 1987 to 2008, and alive at the end of 2011 were eligible for this cross-sectional study performed in 2012/2013. Participants completed a mailed questionnaire. Job status was dichotomized as either employed (paid work) or not-employed (disability and retirement pension, on economic support, home-makers, or students). Results The response rate was 78%, and the sample (N = 312) contained 60% men. Mean age at HDT-ASCT was 44.3 and at survey 54.0 years. At diagnosis 85% of survivors were employed, 77% before and 77% after HDT-ASCT, and 58% at follow-up. Forty seven percent of the survivors were employed at all time points. The not-employed group at survey was significantly older and included significantly more females than the employed group. No significant between-group differences were observed for lymphoma-related variables. Fatigue, mental distress and type D personality were significantly higher among those not-employed, while quality of life was significantly lower compared to the employed group. Older age at survey, being female, work ability and presence of type D personality remained significantly related to being not-employed at survey in the multivariable analysis. Conclusions Our findings show that not-employed long-term survivors after HDT-ASCT for lymphoma have more comorbidity, cognitive problems and higher levels of anxiety/depression than employed survivors. These factors should be checked and eventually treated in order to improve work ability.
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.
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.
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.
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.
One hundred and thirty‐four adults and 204 children were randomized in two prospective, parallel comparative multicentre trials to receive either conventional amphotericin B 1 mg/kg/d (c‐AMB), ...liposomal amphotericin B 1 mg/kg/d (L‐AMB1) or liposomal amphotericin B 3 mg/kg/d (L‐AMB3). Patients were entered if they had a pyrexia of unknown origin (PUO) defined as temperature of 38°C or more, not responding to 96 h of systemic broad‐spectrum antibiotic treatment, and neutropenia (< 0.5 × 109/l). The safety and toxicity of liposomal amphotericin B was compared with that of conventional amphotericin B. Efficacy of treatment was assessed, with success defined as resolution of fever for 3 consecutive days (< 38°C) without the development of any new fungal infection. Clinical and laboratory parameters were collected for safety analysis. In both the paediatric and adult populations, L‐AMB treated patients had a 2–6‐fold decrease in the incidence (P 0.01) of test‐drug‐related side‐effects, compared to c‐AMB. Severe trial‐drug‐related side‐effects were seen in 1% of L‐AMB treated patients, in contrast to 12% of patients on c‐AMB (P < 0.01). Nephrotoxicity, in the patient subset not receiving concomitant nephrotoxic agents, defined as a doubling from the patients baseline serum creatinine level, was not observed in the L‐AMB1 arm whereas the incidence was 3% in patients on L‐AMB3 and 23% in those on c‐AMB (P < 0.01). Moreover, time to develop nephrotoxicity was longer in both L‐AMB arms than c‐AMB (P < 0.01). Severe hypokalaemia was observed less frequently in both L‐AMB arms (P < 0.01).
Analysis was by intention‐to‐treat and included all patients randomized. Success was defined by a minimum of 3 consecutive days with fever (< 38°C) continuing to study end indicated by recovery of neutrophils to 0.5 × 109/l. Addition of systemic antifungal therapy or development of systemic fungal infection were failures as was persistent fever to study end. Efficacy assessments indicated success in 49% of the total group treated with c‐AMB. 58% of patients responded to L‐AMB1 and 64% to L‐AMB3. A statistically significant difference was found between c‐AMB and L‐AMB3 (P = 0.03) but a Kaplan‐Meier analysis of time to deffervescence of fever showed there was no significant difference between the arms.
It was concluded that liposomal amphotericin at either 1 or 3 mg/kg/d was significantly safer than conventional amphotericin B in children and adults. The main aim of this open‐label study was to compare safety between the three trial arms. However, we provide evidence for an equivalent or possibly superior efficacy of liposomal amphotericin with regard to resolution of fever of unknown origin. Subsequent trials should compare amphotericin preparations in defined fungal infections.
Background: To quantify the long-term risk of second cancers (SCs) up to 30 years after primary treatment for Hodgkin’s disease (HD) Material and methods In the period 1968 to 1985, an unselected ...population of 1024 patients started treatment for HD at the Norwegian Radium Hospital (NRH) and were followed for SC from 1969 through 1998 by The Norwegian Cancer Registry. The median age at diagnosis of HD was 40 years, and the median time at follow-up was 14 years. Results: Of 197 SCs, 14 were acute non-lymphocytic leukemia (ANLL), 31 non-Hodgkin’s lymphoma (NHL) and 152 solid cancers. The standardized incidence ratio (SIR) was significantly increased for SCs as a group, and for the subgroups ANLL, NHL, lung cancer, breast cancer, stomach cancer and melanoma. ANLL was related to heavy treatment with chemotherapy (CT) and combined CT and radiotherapy (RT), NHL was not treatment related, and solid tumors were related to radiotherapy only or combined RT and CT. The SIR of ANLL and NHL reached a peak between 5 and 10 years after treatment. Solid and non-solid tumors increased with young age at diagnosis of HD and solid tumors increased with follow-up time up to 28 years Conclusion: In a long-term follow-up study of HD patients of all ages, the SIR of solid tumors was high in patients treated at young age and decreased with increasing age. Most solid tumors had started within or at the edge of the irradiated field, and SIR of solid tumors increased even 20–30 years after diagnosis.
Background: Secondary central nervous system (CNS) involvement by aggressive lymphoma is a well-known and dreadful clinical complication. The incidence and risk factors for CNS manifestation were ...studied in a large cohort of elderly (>60 years) patients with aggressive lymphoma. Patients and methods: In all, 444 previously untreated patients were randomized to receive 3-weekly combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone or cyclophosphamide, mitoxantrone, vincristine and prednisone (CNOP) (doxorubicin substituted by mitoxantrone) chemotherapy with or without filgrastim. Prophylactic intrathecal methotrexate was given to patients with lymphoma involvement of bone marrow, testis and CNS near sites. Results: In all 29 of 444 (6.5%) developed CNS disease after a median observation time of 115 months. CNS was the only site of progression/relapse in 13 patients while part of a systemic disease manifestation in 16 patients. In univariate risk factor analysis, CNS occurrence was associated with extranodal involvement of testis (P = 0.002), advanced clinical stage (P = 0.005) and increased age-adjusted International Prognostic Index score (aaIPI; P = 0.035). In multivariate analysis, initial involvement of testis remained significant and clinical stage was of borderline significance. The median survival time was 2 months after presentation of CNS disease. Conclusion: A significant proportion of elderly patients with advanced aggressive lymphoma will develop CNS disease. CNS occurrence is related to testis involvement, advanced clinical stage and high aaIPI and the prognosis is dismal.
To determine whether a combination of high-dose therapy and autologous stem-cell transplantation (ASCT) is superior to conventional-dose consolidation and maintenance chemotherapy as postremission ...therapy in adults with lymphoblastic lymphoma.
One hundred nineteen patients were entered onto this prospective randomized trial from 37 centers. Patients received standard remission induction therapy, and responding patients were randomized either to continue with a conventional consolidation/maintenance protocol (CC) or to receive high-dose therapy and ASCT. In some centers, patients with HLA-identical sibling donors were registered on the trial but proceeded to allogeneic bone marrow transplantation (BMT) without randomization.
Of the 119 patients entered, 111 were assessable for response to induction therapy. The overall response rate was 82% (56% complete response, 26% partial response). Of the 98 patients eligible for randomization, 65 were randomized, 31 to ASCT and 34 to CC. Reasons for failure to randomize included patient refusal (12 patients), early progression or death on induction therapy (eight patients), excessive toxicity of induction regimen (six patients), and elective allogeneic BMT (12 patients). With a median follow-up of 37 months, the actuarial 3-year relapse-free survival rate is 24% for the CC arm and 55% for the ASCT arm (hazards ratio = 0.55 in favor of the ASCT arm; 95% confidence interval CI, 0.29 to 1.04; P =.065). The corresponding figures for overall survival are 45% and 56%, respectively (hazards ratio = 0.87 in favor of the ASCT arm; 95% CI, 0.42 to 1.81; P =.71).
The use of ASCT in adults with lymphoblastic lymphoma in first remission produced a trend for improved relapse-free survival but did not improve overall survival compared with conventional-dose therapy in this small randomized trial.
We examined retrospectively the outcome of patients with non-Hodgkin's lymphoma (NHL) with systemic involvement of the central nervous system (CNS) registered at The Norwegian Radium Hospital (NRH) ...from 1980 to 1996, in order to evaluate our treatment strategy for these patients. 170 of 2561 patients (6.6%) had CNS involvement, 140 (5.5%) systemic CNS lymphoma (SCNSL) and 30 (1.2%) primary CNS lymphoma (PCNSL). Description of the patients, time of SCNSL diagnosis, symptoms at CNS diagnosis, treatment and survival were registered. The overall median survival for the 140 patients with SCNSL was 2.6 months (95% confidence interval (CI) 2.1–3.2), only 12 patients are alive in complete remission (CR). Patients with CNS involvement at diagnosis, relapse or progression during treatment for NHL had a median survival of 5.4 months (95% CI: 0.3–10.6), 3.8 months (95% CI: 0.0–9.1), and 1.8 months (95% CI: 1.0–2.7), respectively (
P=0.001). 5 of the 8 patients consolidated with high-dose therapy (HDT) are in CR. Paresis was the only symptom that predicted survival for SCNSL. Patients above 60 years of age with CNS involvement at progression or relapse and those with paresis at the time of CNS diagnosis have a dismal prognosis. For these patients supportive therapy only should be considered. For patients under 60 years of age with chemosensitive disease, the trend was toward better prospects, and they should be offered intensive chemo-radiotherapy including HDT with autologous stem cell support.
Abstract Aims Spinal metastatic disease (SMD) is a serious complication of cancer. To our knowledge, only one population-based study of metastatic spinal cord compression (MSCC) has been carried out. ...The purpose of the present study was to describe population-based incidences of SMD that required local treatment, such as radiotherapy, surgery or vertebroplasty, including patients with or without cord compression, and to characterise the neurological status of these patients. Materials and methods During 18 months, all patients with SMD who received local treatment in the South-Eastern Health Region of Norway (population 2.6 million inhabitants) were identified and their medical records were reviewed. Results In total, 1002 patients were included; 83% had multiple lesions in the spine; 39% had SMD at the time of the primary cancer diagnosis. At the start of local treatment, 31% had MSCC and 11% were not able to walk. The prevalence of MSCC at the time of cancer diagnosis was 0.36%. The annual incidences per 100 000 inhabitants were 26.0 for SMD and 8.1 for MSCC. Conclusion Population-based incidences of SMD requiring local treatment have been reported for the first time. The prevalence of MSCC at the time of cancer diagnosis was higher than previously reported. A more precise definition of MSCC and more population-based studies are needed to reduce selection bias when comparing different studies.
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