Hanne Hamre

Gonadal function and parenthood 20 years after treatment for childhood lymphoma: A cross-sectional study†

Gonadal function decades after treatment for childhood lymphoma (CL) is not well described. This cross‐sectional study had two aims: (1) describe long‐term gonadal function and fertility in childhood lymphoma survivors (CLSs), and (2) explore anti‐Mullerian hormone (AMH) as a measure of ovarian function in CLSs.

Factors associated with poor quality of life in survivors of childhood acute lymphoblastic leukemia and lymphoma

Previous studies of health‐related quality of life (QoL) in childhood cancer survivors have hardly focused on factors associated with poor QoL. The aims of our study were: (1) to assess QoL in long‐term survivors (LTSs) of childhood acute lymphoblastic leukemia (ALL) and lymphomas compared to age‐matched controls from the general population (NORMs). (2) To investigate factors associated with poor QoL in LTSs.

Adult survivors of childhood malignant lymphoma are not aware of their risk of late effects

Abstract Purpose. Survivors after malignant lymphoma are at high risk of late effects. In order to take full responsibility for their own health they need knowledge about their diagnosis, treatment and risk of late effects. We assessed such knowledge in adult survivors of childhood malignant lymphoma. Material and methods. In 2007–2009 128 five-year survivors after childhood malignant lymphoma participated in a national cross-sectional questionnaire-based survey combined with clinical examination. [Males: 69, females: 59, treatment period 1970–2000, median age (range) at diagnosis: 14 years (0–18), at survey: 32 years (19–55), Hodgkin lymphoma (HL): 84, Non-Hodgkin lymphoma (NHL): 44]. Prior to the clinical examination a semi-structured interview on the survivors’ knowledge was conducted by a study nurse. The individual survivors’ responses were compared with his/her medical record. Results. One hundred and twenty one reported their diagnosis correctly, seven reported that they had cancer, but could not specify malignant lymphoma. Thirty-three could not differentiate between HL and NHL. One hundred and twenty three reported their treatment modalities correctly (radiotherapy vs. chemotherapy vs. combined). Eighty-five (66%) were not aware of any risks for late effects. The remaining 43 listed at least one of the following late effects; infertility, heart-problems, impaired dental status, hypothyroidism, breast cancer, reduced muscle growth, fatigue and reduced memory or concentration. Thirty-seven survivors who provided additional comments reported that they had received some information about risk of late effects from their therapists. Age at diagnosis or educational level were not associated with knowledge about possible late effects while treatment period was. Conclusions. Norwegian long-term survivors of childhood malignant lymphomas are showing improved level of knowledge of their diagnosis and treatment modalities during the last decade. Still, independent of age at diagnosis and level of education, they are insufficiently aware of their risk of late effects.

Chronic fatigue in long-term survivors of childhood Lymphomas and Leukemia: Persistence and associated clinical factors

Background: Chronic fatigue (CF) is an important late effect after childhood malignancies. Our aim was to assess CF persistence over time, concurrent comorbidities, and associations with clinical symptoms. Procedure: A total of 102 long-term survivors of childhood lymphomas and acute lymphoblastic leukemia, 53 and 49 reporting CF and no CF, respectively, at time point (TP)1, were evaluated for CF at a second TP after a median interval of 2.7 years. At TP2 a survey, including self-reported and objectively measured variables, assessed depressive symptoms, pain, and physical activity. Results: A total of 32 of the 53 reported CF cases at both TPs and 40/49 survivors had no CF at both TPs, whereas 30 had changed their fatigue status between first and second assessment (converters). Major somatic comorbidities were equally distributed among the groups. After exclusion of converters and survivors with major comorbidity/pregnancy, 27 persistent CF (PCF) cases and 35 controls were compared. PCF cases reported significantly more depression, sleeping problems, anxiety, pain, and reduced physical function. Further, they were less physically active than controls (steps/d; P=0.009). In a multiple regression analysis, depressive symptoms remained the only significant predictor of PCF. Conclusions: Long-term survivors of childhood cancer with PCF are characterized by more depressive symptoms, anxiety, pain, insomnia, and less physical activity.

Serum cytokines and chronic fatigue in adults surviving after childhood leukemia and lymphoma

INTRODUCTION Fatigue is a common and distressing symptom in all phases of the cancer trajectory. Chronic fatigue (CF) is defined as fatigue with duration ⩾6months. The etiology of CF in cancer survivors is poorly understood, but a link to inflammatory activity has been suggested. In the present study we explored the relation between CF and the levels of 17 cytokines among a national representative sample of 232 adult survivors after childhood lymphoma and acute lymphoblastic leukemia (ALL). METHODS Chalders fatigue questionnaire assessed CF. The sera of the survivors were analyzed for 27 cytokines, where of 17 were detectable. RESULTS Median age at survey and diagnosis was 29.7years (range 18.6-54.5years) and 9.6years (range 0.3-18.0years), respectively. Median follow-up time was 21.5years (range 7.1-40.0years). CF was not associated with increased levels of any of the 17 detectable cytokines when all three diagnostic groups were included in the analyses. In sub-analyses of the non-Hodgkin lymphoma survivors only, those with CF had significant higher levels of IL-9, FGF, PDGF and eotaxin compared to those without CF (p<0.05). Gender, age, diagnosis, obesity, or reduced heart function did not impact upon the results. Differences in cytokine levels between the diagnostic groups were observed irrespective of the presence/absence of CF. CONCLUSION This study could not confirm a relation between levels of cytokines and CF in adults who survived childhood lymphoma and ALL, except for among NHL survivors. Despite the broad spectrum of cytokines and relatively large sample, small aberrances may not have been traced.

Right ventricular function in long-term adult survivors of childhood lymphoma and acute lymphoblastic leukaemia

AIMS Little is known about right ventricular (RV) function in survivors of childhood cancer, although both anthracyclines and radiotherapy represent potentially cardiotoxic treatment. We hypothesized that adult survivors of childhood malignant lymphoma or acute lymphoblastic leukaemia would have impaired RV function. METHODS AND RESULTS We examined RV dimensions and function by echocardiography in 246 survivors, mean 21.7 years after diagnosis, and in 211 matched controls. Of the survivors, 84% had been exposed to anthracyclines, mediastinal radiotherapy, or both. Compared with controls, all mean measures of RV function were lower in the survivor group: fractional area change (44.5 vs. 48.6%, P < 0.001), tricuspid annular plane systolic excursion (2.24 vs. 2.49 cm, P < 0.001), peak systolic tricuspid annular velocity (12.1 vs. 13.0 cm/s, P < 0.001), and free wall strain (-26.5 vs. -28.4%, P < 0.001). In contrast, there were little differences in RV diastolic dimensions. Lower measures of RV function were found in all survivor subgroups having received cardiotoxic treatment, but not in the 16% of survivors unexposed to anthracyclines or mediastinal radiotherapy. Signs of RV systolic dysfunction were found in 30% of the survivors, and more than 3 times more often in survivors with left ventricular dysfunction. CONCLUSION Long-term survivors of childhood lymphoma or acute lymphoblastic leukaemia frequently have impaired RV function compared with controls. As this is associated with increased risk of heart failure and death in many other conditions, we recommend increased attention to RV function in childhood survivors. Whether RV dysfunction impairs prognosis in this patient group should be examined in longitudinal studies.

Chronic Fatigue in Adult Survivors of Childhood Cancer: Associated Symptoms, Neuroendocrine Markers, and Autonomic Cardiovascular Responses

BACKGROUND Chronic fatigue (CF) is a common late effect after childhood cancer. OBJECTIVE Based on findings among patients with the chronic fatigue syndrome (CFS), this study explored symptoms, neuroendocrine markers, and autonomic cardiovascular responses associated with CFS in childhood cancer survivors. METHODS Long-term survivors of childhood lymphoma and acute lymphoblastic leukemia reporting CF were compared with survivors without CF. Data included patient-reported outcomes, clinical examination, head-up tilt test, and neuroendocrine markers in the blood and the urine. RESULTS Of 102 included survivors, 15 were excluded from comparative analyses because of significant co-morbidity or pregnancy. Of the remaining 87 participants (median age 33.0 years, follow-up time 25.2 years), 35 had CF and 52 did not have CF. Compared with non-CF controls, CF cases reported a significantly (P < 0.01) higher frequency of symptoms typical of the CFS (muscle or joint pain or both and feeling confused/disoriented) and symptoms of autonomic dysfunction (palpitations, feeling intermittently heat and cold, and watery diarrhea). CF cases and controls did not differ regarding autonomic cardiovascular responses to orthostatic stress, but the CF group had lower levels of plasma adrenocorticotrophic hormone (P = 0.002) and higher levels of urine norepinephrine (P = 0.017). CONCLUSIONS Survivors with CF reported a high symptom-burden compared with controls. There were few differences between both the groups regarding biomarkers, but slight alterations of the hypothalamus-pituitary-adrenal axis and sympathetic nervous activity were detected. CF in cancer survivors has features in common with the CFS, but further efforts are required to clarify the pathophysiology.

“Natural course” of disease in patients with metastatic castrate-resistant prostate cancer: Survival and prognostic factors without life-prolonging treatment

Abstract Objective: The aim of this study was to determine survival and prognostic factors in unselected patients with metastatic castrate-resistant prostate cancer (mCRPC), who never received life-prolonging treatment. Materials and methods: The study was a retrospective analysis of a consecutive sample of patients with mCRPC seen at the urological unit of a local hospital from 2000 to 2005, their mCRPC diagnosis based on rising prostate-specific antigen (PSA) during androgen depletion treatment (ADT). Results: Median overall survival was 12.3 months (range 0.2–108 months), the 3 year survival was 16.9% (95% confidence interval 0.11–0.24) and two patients were alive at the end of follow-up. Compared to a PSA nadir of greater than 11 μg/l during ADT, a PSA nadir of less than 1 μg/l significantly decreased the risk of death by 71%. A PSA doubling time less than 1.6 months during the early phase of mCRCP almost tripled the risk of death compared to a PSA doubling time longer than 3 months. Alkaline phosphatase serum levels and hemoglobin levels within the normal range indicated a favorable prognosis. Conclusions: The “natural course” of mCRPC varies without life-prolonging treatment along with PSA nadir during ADT, PSA doubling time, alkaline phosphatase and hemoglobin level at mCRPC diagnosis. 3-year survival or longer is observed in 16.9% of patients. In clinical intervention trials among mCRPC patients, all known prognostic factors should be taken into account during the randomization process and during survival analyses.