- Email: [email protected]
Does persistent fatigue in survivors relate to cancer?
Comment
80–90% of patients with Hodgkin’s lymphoma are cured of their disease, and the ratio of long-term survivors to annual incidence cases has reached almost 20:1 in high-income countries. Three-quarters of new cases are diagnosed before the age of 60 years, and most, if not all, survivors return to normal life, including personal, social, and professional activities. Treatment-related complications first gained attention in the early 1970s with findings of the growth of second cancers followed by a large number of reports as soon as quantification was available on various side-effects. Besides second cancers, the most commonly reported complications are cardiovascular diseases, thyroid and pulmonary insufficiency, and impaired fertility. As concerns mounted about health-related quality of life, more attention was given to patients’ complaints about limitations of their daily life, including persistent fatigue. Prevalence of persistent fatigue has been estimated to be 2·5–3·0 times higher in survivors of Hodgkin’s lymphoma than in the general population.1 In The Lancet Oncology, Stefanie Kreissl and colleagues2 report the results of a 5-year longitudinal study of cancer-related fatigue in patients with Hodgkin’s lymphoma enrolled in three prospective randomised controlled clinical trials conducted by the German Hodgkin Study Group from 2003 to 2009. The trials enrolled patients with either early-stage favourable, early-stage unfavourable, or advancedstage disease. Fatigue assessment was done with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 self-administered questionnaire (one-dimension fatigue scale) at diagnosis (baseline), during chemotherapy, at end of treatment (after involved-field irradiation), and every year thereafter for 5 years. Patients aged 18–60 years were eligible for the study. Individual fatigue scores (range 0–100) were compared with age-specific and sex-specific general German population data and individual absolute differences used. Overall, 4215 patients participated and 3392 provided a baseline assessment. Kreissl and colleagues2 show that mean fatigue scores at baseline were significantly increased by 18·6 (SD 28·6) in HD13, 28·8 (29·9) in HD14, and 37·2 www.thelancet.com/oncology Vol 17 October 2016
(30·6) in HD15, compared with general population data. Fatigue scores increased during treatment to reach the same level irrespective of trial and the amount of chemotherapy given, returned to a level corresponding to the baseline scores of patients with early-stage favourable disease 1 year after the end of treatment, and remained constant afterwards. No clinical characteristics or treatment types affected the fatigue level beyond the first year after the end of treatment except initial fatigue level and age. With prospective data available from before patients started treatment, the researchers confirm the result of previous similar prospective studies within clinical trials, although these were limited to early-stage disease.3,4 They also confirm the level of persistent fatigue measured with the same quality-of-life instrument used by Joly and colleagues5 in a general population cancer registry-based case-control study done in a rural area in France, in which the survivors’ characteristics were very similar to those of the German cohort. Kreissl and colleagues2 applied the growth mixture model, a model initially proposed “to map the developmental course of symptoms and assess heterogeneity in response to clinical interventions”,6 and noted that three to four fatigue trajectories can be distinguished using fatigue data from the best experimental group of each trial. The analyses confirm that: the higher the level of baseline fatigue, the higher the level of persistent fatigue; 36–46% of patients spontaneously return to a fatigue level not different from that of the general population; one-third have their fatigue level improved but still higher than the general population; and 20–27% (ie, those with the highest baseline fatigue score) show no change. The limit of the method is that it cannot provide any information about which patients will belong to which category because it is based on a posteriori data. Other limitations of the study by Kreissl and colleagues2 are the use of a one-dimensional method to assess fatigue, which is a multidimension entity; and the use of clinical trials data only for understanding the pathogenesis of persistent fatigue because potential relevant information is missing. In-depth investigations of the causes and contributing factors
Photo Researchers/Science Photo Library
Does persistent fatigue in survivors relate to cancer?
Published Online September 6, 2016 http://dx.doi.org/10.1016/ S1470-2045(16)30156-5 See Articles page 1453
1351
Comment
of persistent fatigue in long-term cancer survivors are scarce and fewer than 20 reports have focused on lymphoma survivors, including limited cross-sectional descriptive studies.7 No medical explanation exists for why fatigue develops or persists in some patients, and the findings of Kreissl and colleagues2 suggest that persistent fatigue is not related to disease or treatment. Therefore, psychological factors (eg, susceptibility to anxiety or depression) or biological factors such as immunocompetence8 or heritable genetic variations (eg, chemotherapy drug metabolism genetic polymorphisms9) might be playing a part. Before tertiary prevention interventions are undertaken to manage or prevent the development of persistent fatigue, among which exercise-programmes10 and cognitive behavioural therapy7 have been proposed, there is a need to understand the mechanisms by which individuals who develop a cancer are also susceptible to develop abnormal fatigue.
We declare no competing interests. RB is recipient of a fellowship from the Ligue Nationale Contre le Cancer, École Doctorale SIMEM, University of Caen-Normandie, France.
*Michel Henry-Amar, Raphaël Busson
10
Centre de Traitement des Données du Cancéropôle Nord-Ouest, Centre François Baclesse, 14076 Caen cedex 05, France [email protected]
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2
3
4
5
6 7
8
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Hjermstad MJ, Oldervoll L, Fosså SD, et al. Quality of life in long-term Hodgkin’s disease survivors with chronic fatigue. Eur J Cancer 2006; 42: 327–33. Kreissl S, Mueller H, Goergen H, et al. Cancer-related fatigue in patients with and survivors of Hodgkin’s lymphoma: a longitudinal study of the German Hodgkin Study Group. Lancet Oncol 2016; published online Sept 6. http://dx.doi.org/10.1016/S1470-2045(16)30093-6. Ganz PA, Moinpour CM, Pauler DK, et al. Health status and quality of life in patients with early-stage Hodgkin’s disease treated on Southwest Oncology Group Study 9133. J Clin Oncol 2003; 21: 3512–19. Heutte N, Flechtner HH, Mounier N, et al. Quality of life after successful treatment of early-stage Hodgkin’s lymphoma: 10-year follow-up of the EORTC-GELA H8 randomised controlled trial. Lancet Oncol 2009; 10: 1160–70. Joly F, Henry-Amar M, Arveux P, et al. Late psycho-social sequelae in Hodgkin’s disease survivors: A French population-based case-control study. J Clin Oncol 1996; 14: 2444–53. Nagin DS, Odgers CL. Group-based trajectory modeling in clinical research. Annu Rev Clin Psychol 2010; 6: 109–38. Gielissen MFM, Verhagen S, Bleijenberg G. Cognitive behaviour therapy for fatigued cancer survivors: long term follow-up. Br J Cancer 2007; 97: 612–18. Björkholm M, Holm G, Mellstedt H. Immunocompetence in patients with Hodgkin’s disease. In: Lacher MJ, Redman JR (eds): Hodgkin’s disease: The consequences of survival. Philadelphia, PA: Lea & Febiger. 1990. 112–50. Sloan JA, de Andrade M, Decker P, et al. Genetic variations and patient-reported quality of life among patients with lung cancer. J Clin Oncol 2012; 30: 1699–704. Oldervoll LM, Kaasa S, Knobel H, et al. Exercise reduces fatigue in chronic fatigued Hodgkins disease survivors—results from a pilot study. Eur J Cancer 2003; 39: 57–63.
Melanoma screening by non-health-care professionals
Caia Image/Science Photo Library
In Bristol, UK, a local tattoo artist observed a suspicious mole on the lower back of a client, which, because of its position, had evolved without notice. The suggestion from the tattoo artist for the client to seek a medical opinion initiated a rapid review and the successful excision of a malignant melanoma and these sequence of events prompted an idea about augmenting the surveillance of skin cancer. Evidence has accumulated that screening for melanoma by clinicians and patients can have benefits in terms of early diagnosis and mortality.1 Could the education of non-health-care professionals who regularly observe the skin enhance surveillance further? There have been precedents—a Brazilian group had pioneered this approach for tattoo artists with a national scheme that chronicled numerous individual success stories.2 Their approach entailed face-to-face teaching in a dedicated training session. On the basis of this evidence, we commenced 1352
an hour-long educational programme for our local tattoo artists who were selected by a comprehensive mail appeal to all identified high-street providers within the greater Avon area, in Bristol, UK, which has been met with enthusiasm.3 It has focused on skin structure and function; photocarcinogenesis; preventative strategies such as use of sunscreen; standard markers of malignant change within moles; and, importantly, how to broach a topic which would otherwise be tangential to a conventional visit. There are many theoretical advantages to screening for melanoma by non-health-care professionals. They constitute a diverse group of specialities with the fundamental theme that they observe the skin of their customers at close quarters and, often, for more extended periods of time than medical or allied health professionals. Further, dependent upon each group, there is an inherent inspection of sites www.thelancet.com/oncology Vol 17 October 2016
80–90% of patients with Hodgkin’s lymphoma are cured of their disease, and the ratio of long-term survivors to annual incidence cases has reached almost 20:1 in high-income countries. Three-quarters of new cases are diagnosed before the age of 60 years, and most, if not all, survivors return to normal life, including personal, social, and professional activities. Treatment-related complications first gained attention in the early 1970s with findings of the growth of second cancers followed by a large number of reports as soon as quantification was available on various side-effects. Besides second cancers, the most commonly reported complications are cardiovascular diseases, thyroid and pulmonary insufficiency, and impaired fertility. As concerns mounted about health-related quality of life, more attention was given to patients’ complaints about limitations of their daily life, including persistent fatigue. Prevalence of persistent fatigue has been estimated to be 2·5–3·0 times higher in survivors of Hodgkin’s lymphoma than in the general population.1 In The Lancet Oncology, Stefanie Kreissl and colleagues2 report the results of a 5-year longitudinal study of cancer-related fatigue in patients with Hodgkin’s lymphoma enrolled in three prospective randomised controlled clinical trials conducted by the German Hodgkin Study Group from 2003 to 2009. The trials enrolled patients with either early-stage favourable, early-stage unfavourable, or advancedstage disease. Fatigue assessment was done with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 self-administered questionnaire (one-dimension fatigue scale) at diagnosis (baseline), during chemotherapy, at end of treatment (after involved-field irradiation), and every year thereafter for 5 years. Patients aged 18–60 years were eligible for the study. Individual fatigue scores (range 0–100) were compared with age-specific and sex-specific general German population data and individual absolute differences used. Overall, 4215 patients participated and 3392 provided a baseline assessment. Kreissl and colleagues2 show that mean fatigue scores at baseline were significantly increased by 18·6 (SD 28·6) in HD13, 28·8 (29·9) in HD14, and 37·2 www.thelancet.com/oncology Vol 17 October 2016
(30·6) in HD15, compared with general population data. Fatigue scores increased during treatment to reach the same level irrespective of trial and the amount of chemotherapy given, returned to a level corresponding to the baseline scores of patients with early-stage favourable disease 1 year after the end of treatment, and remained constant afterwards. No clinical characteristics or treatment types affected the fatigue level beyond the first year after the end of treatment except initial fatigue level and age. With prospective data available from before patients started treatment, the researchers confirm the result of previous similar prospective studies within clinical trials, although these were limited to early-stage disease.3,4 They also confirm the level of persistent fatigue measured with the same quality-of-life instrument used by Joly and colleagues5 in a general population cancer registry-based case-control study done in a rural area in France, in which the survivors’ characteristics were very similar to those of the German cohort. Kreissl and colleagues2 applied the growth mixture model, a model initially proposed “to map the developmental course of symptoms and assess heterogeneity in response to clinical interventions”,6 and noted that three to four fatigue trajectories can be distinguished using fatigue data from the best experimental group of each trial. The analyses confirm that: the higher the level of baseline fatigue, the higher the level of persistent fatigue; 36–46% of patients spontaneously return to a fatigue level not different from that of the general population; one-third have their fatigue level improved but still higher than the general population; and 20–27% (ie, those with the highest baseline fatigue score) show no change. The limit of the method is that it cannot provide any information about which patients will belong to which category because it is based on a posteriori data. Other limitations of the study by Kreissl and colleagues2 are the use of a one-dimensional method to assess fatigue, which is a multidimension entity; and the use of clinical trials data only for understanding the pathogenesis of persistent fatigue because potential relevant information is missing. In-depth investigations of the causes and contributing factors
Photo Researchers/Science Photo Library
Does persistent fatigue in survivors relate to cancer?
Published Online September 6, 2016 http://dx.doi.org/10.1016/ S1470-2045(16)30156-5 See Articles page 1453
1351
Comment
of persistent fatigue in long-term cancer survivors are scarce and fewer than 20 reports have focused on lymphoma survivors, including limited cross-sectional descriptive studies.7 No medical explanation exists for why fatigue develops or persists in some patients, and the findings of Kreissl and colleagues2 suggest that persistent fatigue is not related to disease or treatment. Therefore, psychological factors (eg, susceptibility to anxiety or depression) or biological factors such as immunocompetence8 or heritable genetic variations (eg, chemotherapy drug metabolism genetic polymorphisms9) might be playing a part. Before tertiary prevention interventions are undertaken to manage or prevent the development of persistent fatigue, among which exercise-programmes10 and cognitive behavioural therapy7 have been proposed, there is a need to understand the mechanisms by which individuals who develop a cancer are also susceptible to develop abnormal fatigue.
We declare no competing interests. RB is recipient of a fellowship from the Ligue Nationale Contre le Cancer, École Doctorale SIMEM, University of Caen-Normandie, France.
*Michel Henry-Amar, Raphaël Busson
10
Centre de Traitement des Données du Cancéropôle Nord-Ouest, Centre François Baclesse, 14076 Caen cedex 05, France [email protected]
1
2
3
4
5
6 7
8
9
Hjermstad MJ, Oldervoll L, Fosså SD, et al. Quality of life in long-term Hodgkin’s disease survivors with chronic fatigue. Eur J Cancer 2006; 42: 327–33. Kreissl S, Mueller H, Goergen H, et al. Cancer-related fatigue in patients with and survivors of Hodgkin’s lymphoma: a longitudinal study of the German Hodgkin Study Group. Lancet Oncol 2016; published online Sept 6. http://dx.doi.org/10.1016/S1470-2045(16)30093-6. Ganz PA, Moinpour CM, Pauler DK, et al. Health status and quality of life in patients with early-stage Hodgkin’s disease treated on Southwest Oncology Group Study 9133. J Clin Oncol 2003; 21: 3512–19. Heutte N, Flechtner HH, Mounier N, et al. Quality of life after successful treatment of early-stage Hodgkin’s lymphoma: 10-year follow-up of the EORTC-GELA H8 randomised controlled trial. Lancet Oncol 2009; 10: 1160–70. Joly F, Henry-Amar M, Arveux P, et al. Late psycho-social sequelae in Hodgkin’s disease survivors: A French population-based case-control study. J Clin Oncol 1996; 14: 2444–53. Nagin DS, Odgers CL. Group-based trajectory modeling in clinical research. Annu Rev Clin Psychol 2010; 6: 109–38. Gielissen MFM, Verhagen S, Bleijenberg G. Cognitive behaviour therapy for fatigued cancer survivors: long term follow-up. Br J Cancer 2007; 97: 612–18. Björkholm M, Holm G, Mellstedt H. Immunocompetence in patients with Hodgkin’s disease. In: Lacher MJ, Redman JR (eds): Hodgkin’s disease: The consequences of survival. Philadelphia, PA: Lea & Febiger. 1990. 112–50. Sloan JA, de Andrade M, Decker P, et al. Genetic variations and patient-reported quality of life among patients with lung cancer. J Clin Oncol 2012; 30: 1699–704. Oldervoll LM, Kaasa S, Knobel H, et al. Exercise reduces fatigue in chronic fatigued Hodgkins disease survivors—results from a pilot study. Eur J Cancer 2003; 39: 57–63.
Melanoma screening by non-health-care professionals
Caia Image/Science Photo Library
In Bristol, UK, a local tattoo artist observed a suspicious mole on the lower back of a client, which, because of its position, had evolved without notice. The suggestion from the tattoo artist for the client to seek a medical opinion initiated a rapid review and the successful excision of a malignant melanoma and these sequence of events prompted an idea about augmenting the surveillance of skin cancer. Evidence has accumulated that screening for melanoma by clinicians and patients can have benefits in terms of early diagnosis and mortality.1 Could the education of non-health-care professionals who regularly observe the skin enhance surveillance further? There have been precedents—a Brazilian group had pioneered this approach for tattoo artists with a national scheme that chronicled numerous individual success stories.2 Their approach entailed face-to-face teaching in a dedicated training session. On the basis of this evidence, we commenced 1352
an hour-long educational programme for our local tattoo artists who were selected by a comprehensive mail appeal to all identified high-street providers within the greater Avon area, in Bristol, UK, which has been met with enthusiasm.3 It has focused on skin structure and function; photocarcinogenesis; preventative strategies such as use of sunscreen; standard markers of malignant change within moles; and, importantly, how to broach a topic which would otherwise be tangential to a conventional visit. There are many theoretical advantages to screening for melanoma by non-health-care professionals. They constitute a diverse group of specialities with the fundamental theme that they observe the skin of their customers at close quarters and, often, for more extended periods of time than medical or allied health professionals. Further, dependent upon each group, there is an inherent inspection of sites www.thelancet.com/oncology Vol 17 October 2016