Tor Ekman

Population Impact of Heart Failure and the Most Common Forms of Cancer A Study of 1 162 309 Hospital Cases in Sweden (1988 to 2004)

Background—The contemporary impact of heart failure (HF) versus the most common forms of cancer as reflected by related first-ever hospitalizations and subsequent case-fatality rates is unknown. Methods and Results—Using a national registry in Sweden, we compared the rate of first-ever hospitalization and associated short- and long-term survival for HF, acute myocardial infarction (AMI), and the most common forms of cancer on an age and sex-specific basis during 1988 to 2004 in 949 733 Swedish patients (1 162 309 hospital admissions in total). Annual incidence of first-ever hospitalization for HF, AMI, and cancer in Sweden were 484, 424, and 373 (lung, colorectal, prostate, and bladder cancer combined) per 100 000 men and 470, 280, and 350 (lung, colorectal, bladder, breast, and ovarian cancer combined) per 100 000 women age >20 years. The ratio of individual cases of HF to cancer was 1.37:1 (465 998 versus 340 738). Despite improvements in 30-day and 5-year survival (adjusted 7% and 6% increase per calendar year for men and women, respectively), HF was associated with unadjusted case-fatality rate of 59% within 5 years and 196 400 deaths versus 58% and 131 000 deaths in patients with cancer. During 10-year follow-up, HF was associated with 66 318 versus 55 364 premature life-years lost than all common forms of cancer in men. In women, the equivalent figures were 59 535 versus 64 533 premature life-years lost. Conclusions—These data confirm that, like most common forms of cancer combined, HF exerts a major health burden in respect to age-adjusted rates of first hospitalization, poor overall survival, and premature life-years lost.

Assessment and management of cancer-related fatigue in adults

Fatigue is one of the most prevalent and distressing symptoms of cancer, and is a common side-effect of many of the treatments available for the management of malignant disease. We critically assess the evidence for cancer-related fatigue and its treatment in adults. Little is known about the cause and mechanisms of fatigue, and research into methods of alleviating the condition has focused on treatment for anaemia and behavioural interventions, such as exercise, both of which are effective in reducing fatigue. Although research into the condition has increased considerably in the past decade, important gaps in knowledge remain.

Testicular lymphoma--a retrospective, population-based, clinical and immunohistochemical study.

From a population-based registry, 35 patients with histologically verified testicular lymphomas were identified: diffuse large B-cell lymphomas (DLBCL) in 33 and peripheral T-cell lymphomas in two cases. Twenty-two patients had localized disease (Pe stage I and II). Twenty-eight patients received systemic chemotherapy, 17 of whom also received intrathecal prophylaxis, and 12 out of these 17 also received radiotherapy to the contralateral testis. In the Pe stage I/II group, 7 out of 21 patients in complete remission (CR) relapsed. In 5 of them the CNS was involved (isolated CNS relapse in three). Remarkably late relapses occurred (up to 127 months). Intrathecal prophylaxis seemed to reduce the frequency of relapses involving the CNS, but the relatively short follow-up (median 45 months, range 34–88, for censored patients) prevents firm conclusions regarding efficacy. The outcome for the stage IV patients was poor, with only 1 out of 11 patients in continuous CR. Immunohistochemical analysis of the DLBCL tumours revealed that 31% had the germinal centre B-cell-like phenotype. CD44 was expressed in all the tumours of stage IV patients but in less than half of the Pe stage I/II patients. A high intratumoural microvessel density was correlated with a high degree of Ki-67 positive tumour cells and an inferior overall survival.

A population-based study of 135 lymphomas after solid organ transplantation: The role of Epstein-Barr virus, hepatitis C and diffuse large B-cell lymphoma subtype in clinical presentation and survival.

Abstract Background. Epstein-Barr virus (EBV) plays a major role in the development of post-transplant lymphoproliferative disorder (PTLD), but there is an increasing awareness of EBV-negative PTLD. The clinical presentation of EBV-negative PTLD has not been as well characterised as EBV-positive cases. Further, there is limited knowledge on the clinical importance of diffuse large B-cell lymphoma (DLBCL) cell of origin subtype post-transplant. Materials and methods. We studied the role of EBV, hepatitis C (HCV) and DLBCL subtype in clinical presentation and survival in 135 post-transplant lymphomas diagnosed 1980–2006 in a population-based cohort of 10 010 Swedish solid organ transplant recipients. The lymphomas were re-evaluated according to WHO 2008, examined for EBV, and clinical data were collected from medical records. Results. Lymphoma incidence rate was 159/100 000 person-years and is also reported by lymphoma subtype. EBV-negative lymphomas constituted 48% and were associated with HCV infection (p = 0.02), bone marrow involvement (p < 0.001), and T-cell phenotype (p = 0.002). Among DLBCL, 78% were of non-germinal centre subtype, which was associated with EBV-positivity (69%, p = 0.001), early occurrence (p = 0.03), heart/liver/lung/pancreas recipients (p = 0.02), anti-T-cell globulin (p = 0.001), and tacrolimus treatment (p = 0.02). DLBCL subtypes had similar overall survival. Five-year overall survival was 42% in all treated patients. Independent poor prognostic factors were older age, B symptoms, ECOG 2-4, kidney/pancreas/heart recipients, T-cell lymphoma, and HCV-infection. Conclusions. With long follow-up, a large part of PTLD is EBV-negative, due to a high proportion of T-cell lymphomas and low of polymorphic PTLD. EBV-negative PTLD have a different clinical presentation. HCV may play an aetiological role in late-onset PTLD and was revealed as a new prognostic factor for inferior survival that needs to be confirmed in larger studies. The heavier immunosuppression in non-kidney transplantations seems to play a role in the development of non-germinal centre DLBCL. DLBCL cell of origin subtype lacks prognostic importance in the transplant setting.

Gut Toxicity During Hemopoietic Stem Cell Transplantation May Predict Acute Graft-Versus-Host Disease Severity in Patients

Graft-versus-host disease (GVHD) is the primary complication of allogeneic, hemopoietic, stem cell transplantation (HSCT). Murine models suggest that gut toxicity, induced by the intensive chemotherapy preceding hematopoietic stem cell infusion, aggravates systemic GVHD. In HSCT patients gut toxicity correlates with chemotherapy intensity. The present study investigates acute GVHD severity and intestinal toxicity in patients undergoing allogeneic HSCT. In 38 patients intestinal permeability was assessed before and after chemotherapy (on days −1, +4, +7 and +14 as related to the stem cell infusion). Cumulative acute GVHD (days 0–100) and clinical intestinal toxicity (days 0–14) were evaluated in parallel. Patients with mild, acute GVHD (grades 0–I) had better-preserved intestinal barrier function (P=0.04) and less pronounced cumulative clinical intestinal toxicity (P=0.02) compared with patients with more severe acute GVHD (grades II–IV). Gut toxicity predicts acute GVHD severity. Therefore, gut protective strategies may diminish GVHD severity in allogeneic HSCT patients.

Treatment outcome in patients younger than 60 years with advanced stages (IIB-IV) of Hodgkin's disease : the Swedish National Health Care Programme experience.

Abstract: Background –Despite improved treatment results achieved in Hodgkins disease (HD), only about 70% of patients with advanced stages are cured. The primary aim of this study was to evaluate the outcome of advanced stages (IIB–IVB) of HD in younger patients in an unselected population‐based group of patients. The patients were recommended individualized treatment with respect to number of chemotherapy (CT) courses and post‐CT radiotherapy (RT) based on pretreatment characteristics and tumour response. Secondly, we investigated if variables of prognostic importance could be detected. Patients and methods –Between 1985–92, 307 patients between 17–59 yr of age (median 36) were diagnosed with HD in stages IIB–IVB in 5/6 health care regions in Sweden. Median follow‐up time was 7.8 yr (1.3–13). Retrospectively, laboratory parameters were collected. Results –In total, 267 (87%) patients had a complete response (CR). The overall and disease‐free 10‐yr survivals in the whole cohort were 76% and 67%, respectively. There was no difference in survival between the groups of patients who received 6 or 8 cycles of CT. Survival was not higher for patients in CR after CT when RT was added. For those in PR after CT, additional RT raised the frequencies of CR. A selected group of pathologically staged patients was successfully treated with a short course (2 cycles) of CT+RT. In univariate analyses survival was affected by age, stage IVB, bone‐marrow involvement, B‐symptoms, S‐LDH, S‐Alb and reaching CR or not after 2, 4 and 6 cycles of CT. In a multivariate analysis, age and reaching CR after 6 cycles of CT remained statistically significant. Conclusions –The lack of difference in survival between the groups of patients who received 6 versus 8 cycles of CT indicates a successful selection of patients for the shorter treatment. Reaching a rapid CR significantly affected outcome. Whether some patients need less CT than the generally recommended 8 courses can properly only be evaluated in a randomised study. Additional RT may play a role in successful outcome, particularly if residual tumours are present, but its precise role can also only be defined in prospectively randomised studies. Reaching CR after CT was the most important variable affecting survival besides age.

Anal carcinoma - Survival and recurrence in a large cohort of patients treated according to Nordic guidelines

OBJECTIVE To evaluate treatment outcome in a large population-based cohort of patients with anal cancer treated according to Nordic guidelines. MATERIAL Clinical data were collected on 1266 patients with anal squamous cell carcinoma diagnosed from 2000 to 2007 in Sweden, Norway and Denmark. 886 of the patients received radiotherapy 54-64Gy with or without chemotherapy (5-fluorouracil plus cisplatin or mitomycin) according to different protocols, stratified by tumor stage. RESULTS High age, male gender, large primary tumor, lymph node metastases, distant metastases, poor performance status, and non-inclusion into a protocol were all independent factors associated with worse outcome. Among patients treated according to any of the protocols, the 3-year recurrence-free survival ranged from 63% to 76%, with locoregional recurrences in 17% and distant metastases in 11% of patients. The highest rate of inguinal recurrence (11%) was seen in patients with small primary tumors, treated without inguinal irradiation. CONCLUSIONS Good treatment efficacy was obtained with Nordic, widely implemented, guidelines for treatment of anal cancer. Inguinal prophylactic irradiation should be recommended also for small primary tumors.

A population-based study of the outcome for patients with first relapse of Hodgkin's lymphoma

Abstract: Background : Our aims were to evaluate the response to salvage treatment in relation to initial treatment and to evaluate prognostic factors at the time of relapse in an unselected population of relapsing patients with Hodgkins lymphoma (HL). Patients and methods : In total, 124 patients younger than 60 yr of age with initial diagnosis of HL in Sweden relapsed between 1985 and 1995. Results : Fifty‐eight patients relapsed after initial treatment with radiotherapy (RT) only, 62 after combination chemotherapy (CT), of whom 30 had received additional involved‐field RT, and four after a short course of CT followed by extended‐field RT. For 37 patients among the 58 relapsers after initial RT treated according to the recommendations of the National guidelines, the 5‐yr Hodgkin‐specific survival (HLS) was 85%, overall survival (OS) 73% and event‐free survival (EFS) 62%, which is not inferior to survival in patients with primarily advanced stages. It was poorer in the 21 patients who initially had received RT only, even though they had been recommended for more extensive treatment. For patients initially treated with a full course (6–8 cycles) of CT the 5‐yr HLS was 60%, OS 58% and EFS 22%. Bulky disease and age at diagnosis strongly affected survival in a multivariate analysis. Conclusions : Patients initially treated with RT who relapse have a favourable outcome, provided they have been treated according to the recommendations of the guidelines at the time of diagnosis. Initially bulky disease and, as a consequence, additional RT as part of the initial treatment negatively affect survival at relapse in patients initially treated with a full course of CT.

Early and intermediate stage Hodgkin's lymphoma - report from the Swedish National Care Programme

Abstract: In Sweden a National Care Programme provides treatment principles for Hodgkins lymphoma (HL) since 1985, for early and intermediate stages often less extensive than international recommendations. The purpose is to evaluate long‐term results of these principles. A total of 308 patients (167 men and 141 women), 17–59 yr old (median 31), diagnosed during 1985–92, pathological stage (PS) I‐III1A and I‐IIB and clinical stage (CS) I‐IIA, mean follow‐up 8.8 yr, were studied. Staging laparotomy was recommended in CS IIA. Recommended treatment was mantle or mini‐mantle radiotherapy (RT) alone in CS IA, and PS I‐IIA and subtotal nodal irradiation in PS III1A if the disease was not bulky. Patients in PS I‐IIA and III1A with bulky disease, and PS I‐IIB received one cycle of mechlorethamine, vincristine, prednisone, procarbazine/doxorubicin, bleomycin, vinblastine, lacarbazine (MOPP/ABVD) before irradiation. The remaining patients received three to four cycles of MOPP/ABVD with RT to bulky disease. Relapse‐free (RFS), Hodgkin specific (HLS), and overall survival (OS) at 10 yr were 74%, 92% and 85%. In the individual stages, RFS ranged from 53% (PSIII1A) to 90% (PS IA). RFS (P  = 0.006), HLS, and OS were significantly better in patients treated with chemotherapy compared with those treated with RT alone, especially in patients with bulky disease (P = 0.0005). The international prognostic score did not provide any prognostic information. The OS rates are in agreement with results from international centres during that time. The recommended treatment was sufficient to produce the desired results of <20–30% recurrences, except in PS III1A. Most relapses could be salvaged. Patients with risk factors treated with one MOPP/ABVD and RT had an excellent outcome, superior to those without risk factors treated with RT alone. These results favour the trend to treat early and intermediate stages with a short course of chemotherapy followed by limited RT.

Exploring a Link Between Fatigue and Intestinal Injury During Pelvic Radiotherapy

BACKGROUND The association between cancer-related fatigue and pathological processes in the body is largely unknown. This study was designed to investigate a possible linkage between fatigue and intestinal injury during pelvic radiotherapy. METHODS Twenty-nine women undergoing pelvic radiotherapy for anal or uterine cancer were prospectively followed. Fatigue and diarrhea were assessed using patient self-reported questionnaires. Plasma citrulline concentration, as a sign of intestinal injury, and C-reactive protein, orosomucoid, albumin, α(1)-antitrypsin, and haptoglobin, as signs of systemic inflammation, were analyzed. RESULTS Fatigue increased significantly (p < .001) and citrulline decreased significantly (p < .001) during treatment. A significant negative correlation (r = -0.40; p < .05) was found between fatigue and epithelial atrophy in the intestine (as assessed by plasma citrulline) after 3 weeks of treatment and a significant positive correlation (r = 0.75; p < .001) was found between fatigue and diarrhea. Signs of systemic inflammation were evident, with significant increases in serum orosomucoid, serum haptoglobin (p < .05) and serum α(1)-antitrypsin (p < .001) and a significant decrease in serum albumin (p < .001). CONCLUSION The present study indicates a link between fatigue and intestinal injury during pelvic radiotherapy. This observation should be considered as a preliminary finding because of the small sample size but may serve as a rationale for therapeutic interventions aimed at alleviating both fatigue and gastrointestinal symptoms during pelvic radiotherapy.