Fatigue in cancer treatment - assessment, course and etiology

Aims. The major aims of the present work were to increase the understanding of cancer related fatigue with respect to assessment methodology, frequency and possible etiology. The validity of two fatigue instruments was evaluated and compared in order to enable an evaluation of the fatigue assessments in different patient cohorts. Secondly, the frequency and course of fatigue during curative cancer treatment, as well as the frequency of fatigue in cancer survivors were investigated in order to demonstrate the symptom burden during treatment and after ending curative treatment. The tertiary aim was to explore possible etiologic factors that may explain fatigue in cancer survivors. Background: The long term survival of cancer patients has risen dramatically during the last decades. Several follow-up studies have shown that the long term side effects of curative treatment are more pronounced than first expected. During the last years much more attention have been given to the need for systematic follow up and assessment of long term effects on objective and subjective health after curative treatment. Fatigue is reported to be one of the most frequent and disturbing symptom in cancer patients in general, and is experienced by cancer patients at all stages of their disease. Fatigue is also observed as a subjective late effect in cancer survivors. The prevalence of chronic fatigue (elevated fatigue levels > 6 months) is 2-3 times higher in Hodgkin´s Disease Survivors (HDS) than in the general population. Despite the high prevalence of fatigue, the etiology and causes of the symptom is not clear. Most studies of fatigue in cancer patients are cross sectional and of limited value when exploring the frequency and contributing factors to the etiology. Since fatigue is a subjective phenomenon, it is agreed that it should be measured by patients self assessment. Several instruments are developed for fatigue measurement, both uni - and multi -dimensional. As in research in general, the validity of the subjective outcomes are of crucial importance. Methods: Five different studies were conducted in order to meet the major aims. Two aspects of the validity of the fatigue scale in the health related quality of life (HRQoL) questionnaire EORTC QLQ-C30 were addressed, the dimensionality of the fatigue scale (FA) and the sensitivity of the FA. The instruments were evaluated in two different patient cohorts, a palliative patients cohort and a cohort of hematooncological malignancy patients after curative treatment. A longitudinal follow up study of HRQoL and fatigue in lymphoma and leukaemia patient before, during and until three to five years post treatment with high dose chemotherapy and stem cell support was conducted in order to evaluate the trajectory of fatigue and HRQoL during and after treatment, and to compare symptom and function levels between the cohorts. The relationship between fatigue and late effects of pulmonary, cardiac and endocrine function as well as brain MRI abnormalities were investigated in order to explore possible etiologic factors of fatigue in lymphoma survivors after transplant therapy and in HDS after standard treatment. Findings: The EORTC QLQ-C30 fatigue scale is one - dimensional measuring physical fatigue. A floor/ceiling effect illustrated a poor sensitivity of the scale in patients with lowest respectively highest fatigue level. According to the longitudinal study lymphoma patients report more fatigue, poorer functioning and poorer quality of life as compared to leukaemia patients three to five years after post transplant and as compared to the general population. This pattern was also observed at baseline before transplant. Pulmonary dysfunction was associated with fatigue in HDS whereas cardiac and thyroid dysfunction as late effects after curative treatment did not explain high levels of fatigue in HDS. A questionable association between fatigue and thyroid and gonadal dysfunction were observed. Neither cytokines nor brain white matter lesions were associated with fatigue in HDS. Conclusion: The fatigue subscale, FA, of the EORTC QLQ C30 is measuring physical fatigue. The ability of FA to discriminate between patients with different levels of fatigue is poorer as compared to a fatigue specific instrument (Fatigue Questionnaire). The validation of instruments in different cohorts with differences in frequency and intensity of symptoms is important. As illustrated in earlier studies, fatigue is a prevalent symptom in lymphoma patients before and after treatment indicating that fatigue may be related to the lymphoma disease. Pulmonary late effects was predictor of fatigue in HDS, and the explanatory value of cardiac and endocrine late effects need further investigation. Follow-up program that extend 15-20 years post treatment should be considered in order to explore the effect of clinical relevant medical late effects on subjective health including fatigue

Improving assessment quality in professional higher education: Could external peer review be the answer?

Summative assessment in professional higher education is important for student learning and making sound decisions about advancement and certification. Despite rigorous pre-test quality assurance procedures, problematic assessment items are always discovered post-test. This article examines the implementation of external peer review of items by clinicians in a six-year undergraduate medical programme. The purpose of the article is to identify to what extent clinicians consider multiple choice items to be acceptable for use in examinations, and what comments they provide on items they believe should be revised or not be used at all. 170 clinicians were recruited and reviewed 1353 multiple choice questions. Results showed that one out of five items reviewed were not approved. There were three main reasons for not approving items: (i) relevance of item content, (ii) accuracy of item content and (iii) technical item writing flaws. The article provides insight into a promising quality assurance procedure suitable for in-house examinations in professional higher education

Adjuvant chemotherapy and postoperative radiotherapy in high-risk soft tissue sarcoma patients defined by biological risk factors—A Scandinavian Sarcoma Group study (SSG XX)

Purpose: To investigate the outcome following adjuvant doxorubicin and ifosfamide in a prospective non-randomised study based on a soft tissue sarcoma (STS) patient subgroup defined by specific morphological characteristics previously shown to be at a high-risk of metastatic relapse. The expected 5-year cumulative incidence of metastases in patients with this risk profile has previously been reported to be about 50% without adjuvant chemotherapy. Methods: High-risk STS was defined as high-grade morphology (according to the Fédération Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade II–III) and either vascular invasion or at least two of the following criteria: tumour size ≥8.0 cm, infiltrative growth and necrosis. Six cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2) were given. Postoperative accelerated radiotherapy was applied and scheduled between cycles 3 and 4. Results: For the 150 eligible patients, median follow-up time for metastases-free survival was 3.9 years (range 0.2–8.7). Five-year metastases-free survival (MFS) was 70.4% (95% confidence interval [CI]: 63.1–78.4) with a local recurrence rate of 14.0% (95% CI: 7.8–20.2). For overall survival (OS), the median follow-up time was 4.4 years (range: 0.2–8.7). The five-year OS was 76.1% (95% CI: 68.8–84.2). Tumour size, deep location and reduced dose intensity (<80%) had a negative impact on survival. Toxicity was moderate with no treatment-related death. Conclusions: A benefit of adjuvant chemotherapy, compared to similar historical control groups, was demonstrated in STS patients with defined poor prognostic factors. Vascular invasion, tumour size, growth pattern and necrosis may identify patients in need of adjuvant chemotherapy

Detection of recurrent prostate cancer with 18F-Fluciclovine PET/MRI

Objective: Simultaneous PET/MRI combines soft-tissue contrast of MRI with high molecular sensitivity of PET in one session. The aim of this prospective study was to evaluate detection rates of recurrent prostate cancer by 18F-fluciclovine PET/MRI. Methods: Patients with biochemical recurrence (BCR) or persistently detectable prostate specific antigen (PSA), were examined with simultaneous 18F-fluciclovine PET/MRI. Multiparametric MRI (mpMRI) and PET/MRI were scored on a 3-point scale (1-negative, 2-equivocal, 3-recurrence/metastasis) and detection rates (number of patients with suspicious findings divided by total number of patients) were reported. Detection rates were further stratified based on PSA level, PSA doubling time (PSAdt), primary treatment and inclusion criteria (PSA persistence, European Association of Urology (EAU) Low-Risk BCR and EAU High-Risk BCR). A detailed investigation of lesions with discrepancy between mpMRI and PET/MRI scores was performed to evaluate the incremental value of PET/MRI to mpMRI. The impact of the added PET acquisition on further follow-up and treatment was evaluated retrospectively. Results: Among patients eligible for analysis (n=84), 54 lesions were detected in 38 patients by either mpMRI or PET/MRI. Detection rates were 41.7% for mpMRI and 39.3% for PET/MRI (score 2 and 3 considered positive). There were no significant differences in detection rates for mpMRI versus PET/MRI. Disease detection rates were higher in patients with PSA≥1ng/mL than in patients with lower PSA levels but did not differ between patients with PSAdt above versus below 6 months. Detection rates in patients with primary radiation therapy were higher than in patients with primary surgery. Patients categorized as EAU Low-Risk BCR had a detection rate of 0% both for mpMRI and PET/MRI. For 15 lesions (27.8% of all lesions) there was a discrepancy between mpMRI score and PET/MRI score. Of these, 10 lesions scored as 2-equivocal by mpMRI were changed to a more definite score (n=4 score 1 and n=6 score 3) based on the added PET acquisition. Furthermore, for 4 of 10 patients with discrepancy between mpMRI and PET/MRI scores, the added PET acquisition had affected the treatment choice. Conclusion: Combined 18F-fluciclovine PET/MRI can detect lesions suspicious for recurrent prostate cancer in patients with a range of PSA levels. Combined PET/MRI may be useful to select patients for appropriate treatment, but is of limited use at low PSA values or in patients classified as EAU Low-Risk BCR, and the clinical value of 18F-fluciclovine PET/MRI in this study was too low to justify routine clinical use

Using clinical research networks to assess severity of an emerging influenza pandemic

BACKGROUND: Early clinical severity assessments during the 2009 influenza A H1N1 pandemic (pH1N1) overestimated clinical severity due to selection bias and other factors. We retrospectively investigated how to use data from the International Network for Strategic Initiatives in Global HIV Trials, a global clinical influenza research network, to make more accurate case fatality ratio (CFR) estimates early in a future pandemic, an essential part of pandemic response. METHODS: We estimated the CFR of medically attended influenza (CFRMA) as the product of probability of hospitalization given confirmed outpatient influenza and the probability of death given hospitalization with confirmed influenza for the pandemic (2009-2011) and post-pandemic (2012-2015) periods. We used literature survey results on health-seeking behavior to convert that estimate to CFR among all infected persons (CFRAR). RESULTS: During the pandemic period, 5.0% (3.1%-6.9%) of 561 pH1N1-positive outpatients were hospitalized. Of 282 pH1N1-positive inpatients, 8.5% (5.7%-12.6%) died. CFRMA for pH1N1 was 0.4% (0.2%-0.6%) in the pandemic period 2009-2011 but declined 5-fold in young adults during the post-pandemic period compared to the level of seasonal influenza in the post-pandemic period 2012-2015. CFR for influenza-negative patients did not change over time. We estimated the 2009 pandemic CFRAR to be 0.025%, 16-fold lower than CFRMA. CONCLUSIONS: Data from a clinical research network yielded accurate pandemic severity estimates, including increased severity among younger people. Going forward, clinical research networks with a global presence and standardized protocols would substantially aid rapid assessment of clinical severity