VOLUME
33
䡠
NUMBER
13
䡠
MAY
1
2015
JOURNAL OF CLINICAL ONCOLOGY
C O R R E S P O N D E N C E
Reply to A. Molfino et al
Ørnulf Paulsen Telemark Hospital Trust, Skien; Norwegian University of Science and Technology, Trondheim, Norway
We thank Molfino et al1 for their thoughtful comments regarding our article.2 Anorexia is a burdensome symptom for patients with cancer, and is significantly associated with survival.3 Anorexia is associated with systemic inflammatory response in cancer.4 Therefore, loss of appetite was chosen as a secondary outcome in our trial assessing the effects of methylprednisolone for cancer pain. Our trial showed a significant improvement of appetite loss, which coincides with the findings of Yennurajalingam et al.5 They also found a significant improvement in anorexia using the Functional Assessment of Anorexia/Cachexia Therapy subscale of 4.89 points on day 15 (P ⫽ .013) in favor of the dexamethasone group as compared with the placebo group. As Molfino et al1 correctly point out, appetite is only one part of the symptom complex causing anorexia and reduced food intake. In addition to appetite, changes in taste and GI motility are important, together with secondary factors caused by the disease itself or the treatment, such as stomatitis, diarrhea, and constipation. Furthermore, food intake is an important item to measure separately, as it shows only a weak association with loss of appetite.6 Consequently, it is recommended to assess all these symptoms as well as food intake in cancer cachexia trials.7 Different assessment tools have been proposed to assess the anorexia symptom, including the Functional Assessment of Anorexia/ Cachexia Therapy, which rates the intensity of anorexia and cachexia and the related symptoms on a verbal rating scale 0 to 4. The abridged Patient-Generated Subjective Global Assessment assesses the symptoms on a yes or no basis together with nutritional and functional levels.8 Finally, loss of appetite can be quantitatively evaluated by a numeric rating scale like the Edmonton Symptom Assessment System, and the European Association for Palliative Care minimum data set,9 or health-related quality-of-life tools like the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). Loss of appetite can be measured by the EORTC QLQ-C30 in a reliable way.10 Indeed, the EORTC group is currently developing a lack of appetite item bank for computer-adaptive testing as a further development of this single item. Due to the risk of adverse effects in prolonged use, it is generally agreed that corticosteroids should be used to treat anorexia in the end-of-life setting.11 In patients with short life expectancy, the primary foci are symptom control and quality of life. Therefore, patientreported outcomes are recommended at this stage of disease, and only a minor improvement in appetite may be important to the patients. The risk of adverse effects from the use of high-dose corticosteroids is substantial. This needs to be assessed and may counterbalance the positive effects on appetite.
Nina Aass Oslo University Hospital; University of Oslo, Oslo, Norway
Pål Klepstad St Olavs Hospital, Trondheim University Hospital; Norwegian University of Science and Technology, Trondheim, Norway
Stein Kaasa Norwegian University of Science and Technology; St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
ACKNOWLEDGMENT
Supported by unrestricted grants from the Telemark Hospital Trust, and the South-Eastern Norway Regional Health Authority. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the authors are available with this article at www.jco.org. REFERENCES 1. Molfino A, Muscaritoli M, Rossi Fanelli F: Anorexia assessment in patients with cancer: A crucial issue to improve the outcome. J Clin Oncol 33:1513, 2015 2. Paulsen O, Klepstad P, Rosland JH, et al: Efficacy of methylprednisolone on pain, fatigue, and appetite loss in patients with advanced cancer using opioids: A randomized, placebo-controlled, double-blind trial. J Clin Oncol 32:3221-3228, 2014 3. Laird BJ, Kaasa S, McMillan DC, et al: Prognostic factors in patients with advanced cancer: A comparison of clinicopathological factors and the development of an inflammation-based prognostic system. Clin Cancer Res 19:5456-5464, 2013 4. Laird BJ, McMillan DC, Fayers P, et al: The systemic inflammatory response and its relationship to pain and other symptoms in advanced cancer. Oncologist 18:1050-1055, 2013 5. Yennurajalingam S, Frisbee-Hume S, Palmer JL, et al: Reduction of cancer-related fatigue with dexamethasone: A double-blind, randomized, placebo-controlled trial in patients with advanced cancer. J Clin Oncol 31:30763082, 2013 6. Solheim TS, Blum D, Fayers PM, et al: Weight loss, appetite loss and food intake in cancer patients with cancer cachexia: Three peas in a pod? Analysis from a multicenter cross sectional study. Acta Oncol 53:539-546, 2014 7. Fearon K, Strasser F, Anker SD, et al: Definition and classification of cancer cachexia: An international consensus. Lancet Oncol 12:489-495, 2011 8. Vigano AL, di Tomasso J, Kilgour RD, et al: The abridged Patient-Generated Subjective Global Assessment is a useful tool for early detection and characterization of cancer cachexia. J Acad Nutr Diet 114:1088-1098, 2014 9. Sigurdardottir KR, Kaasa S, Rosland JH, et al: The European Association for Palliative Care basic dataset to describe a palliative care cancer population: Results from an international Delphi process. Palliat Med 28:463-473, 2014 10. Kaasa S, Bjordal K, Aaronson N, et al: The EORTC core quality of life questionnaire (QLQ-C30): Validity and reliability when analysed with patients treated with palliative radiotherapy. Eur J Cancer 31A:2260-2263, 1995 11. Radbruch L, Elsner F, Trottenberg P, et al: Clinical Practice Guidelines on Cancer Cachexia in Advanced Cancer Patients. 2010. http://www.epcrc.org/ guidelines.php?p⫽cachexia
DOI: 10.1200/JCO.2014.60.6475; published online ahead of print at www.jco.org on March 9, 2015
■ ■ ■
Journal of Clinical Oncology, Vol 33, No 13 (May 1), 2015: pp 1513
© 2015 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on June 25, 2016. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
1513
Correspondence
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Reply to A. Molfino et al The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Ørnulf Paulsen No relationship to disclose
Pål Klepstad No relationship to disclose
Nina Aass No relationship to disclose
Stein Kaasa No relationship to disclose
© 2015 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Downloaded from jco.ascopubs.org on June 25, 2016. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
33
䡠
NUMBER
13
䡠
MAY
1
2015
JOURNAL OF CLINICAL ONCOLOGY
C O R R E S P O N D E N C E
Reply to A. Molfino et al
Ørnulf Paulsen Telemark Hospital Trust, Skien; Norwegian University of Science and Technology, Trondheim, Norway
We thank Molfino et al1 for their thoughtful comments regarding our article.2 Anorexia is a burdensome symptom for patients with cancer, and is significantly associated with survival.3 Anorexia is associated with systemic inflammatory response in cancer.4 Therefore, loss of appetite was chosen as a secondary outcome in our trial assessing the effects of methylprednisolone for cancer pain. Our trial showed a significant improvement of appetite loss, which coincides with the findings of Yennurajalingam et al.5 They also found a significant improvement in anorexia using the Functional Assessment of Anorexia/Cachexia Therapy subscale of 4.89 points on day 15 (P ⫽ .013) in favor of the dexamethasone group as compared with the placebo group. As Molfino et al1 correctly point out, appetite is only one part of the symptom complex causing anorexia and reduced food intake. In addition to appetite, changes in taste and GI motility are important, together with secondary factors caused by the disease itself or the treatment, such as stomatitis, diarrhea, and constipation. Furthermore, food intake is an important item to measure separately, as it shows only a weak association with loss of appetite.6 Consequently, it is recommended to assess all these symptoms as well as food intake in cancer cachexia trials.7 Different assessment tools have been proposed to assess the anorexia symptom, including the Functional Assessment of Anorexia/ Cachexia Therapy, which rates the intensity of anorexia and cachexia and the related symptoms on a verbal rating scale 0 to 4. The abridged Patient-Generated Subjective Global Assessment assesses the symptoms on a yes or no basis together with nutritional and functional levels.8 Finally, loss of appetite can be quantitatively evaluated by a numeric rating scale like the Edmonton Symptom Assessment System, and the European Association for Palliative Care minimum data set,9 or health-related quality-of-life tools like the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). Loss of appetite can be measured by the EORTC QLQ-C30 in a reliable way.10 Indeed, the EORTC group is currently developing a lack of appetite item bank for computer-adaptive testing as a further development of this single item. Due to the risk of adverse effects in prolonged use, it is generally agreed that corticosteroids should be used to treat anorexia in the end-of-life setting.11 In patients with short life expectancy, the primary foci are symptom control and quality of life. Therefore, patientreported outcomes are recommended at this stage of disease, and only a minor improvement in appetite may be important to the patients. The risk of adverse effects from the use of high-dose corticosteroids is substantial. This needs to be assessed and may counterbalance the positive effects on appetite.
Nina Aass Oslo University Hospital; University of Oslo, Oslo, Norway
Pål Klepstad St Olavs Hospital, Trondheim University Hospital; Norwegian University of Science and Technology, Trondheim, Norway
Stein Kaasa Norwegian University of Science and Technology; St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
ACKNOWLEDGMENT
Supported by unrestricted grants from the Telemark Hospital Trust, and the South-Eastern Norway Regional Health Authority. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the authors are available with this article at www.jco.org. REFERENCES 1. Molfino A, Muscaritoli M, Rossi Fanelli F: Anorexia assessment in patients with cancer: A crucial issue to improve the outcome. J Clin Oncol 33:1513, 2015 2. Paulsen O, Klepstad P, Rosland JH, et al: Efficacy of methylprednisolone on pain, fatigue, and appetite loss in patients with advanced cancer using opioids: A randomized, placebo-controlled, double-blind trial. J Clin Oncol 32:3221-3228, 2014 3. Laird BJ, Kaasa S, McMillan DC, et al: Prognostic factors in patients with advanced cancer: A comparison of clinicopathological factors and the development of an inflammation-based prognostic system. Clin Cancer Res 19:5456-5464, 2013 4. Laird BJ, McMillan DC, Fayers P, et al: The systemic inflammatory response and its relationship to pain and other symptoms in advanced cancer. Oncologist 18:1050-1055, 2013 5. Yennurajalingam S, Frisbee-Hume S, Palmer JL, et al: Reduction of cancer-related fatigue with dexamethasone: A double-blind, randomized, placebo-controlled trial in patients with advanced cancer. J Clin Oncol 31:30763082, 2013 6. Solheim TS, Blum D, Fayers PM, et al: Weight loss, appetite loss and food intake in cancer patients with cancer cachexia: Three peas in a pod? Analysis from a multicenter cross sectional study. Acta Oncol 53:539-546, 2014 7. Fearon K, Strasser F, Anker SD, et al: Definition and classification of cancer cachexia: An international consensus. Lancet Oncol 12:489-495, 2011 8. Vigano AL, di Tomasso J, Kilgour RD, et al: The abridged Patient-Generated Subjective Global Assessment is a useful tool for early detection and characterization of cancer cachexia. J Acad Nutr Diet 114:1088-1098, 2014 9. Sigurdardottir KR, Kaasa S, Rosland JH, et al: The European Association for Palliative Care basic dataset to describe a palliative care cancer population: Results from an international Delphi process. Palliat Med 28:463-473, 2014 10. Kaasa S, Bjordal K, Aaronson N, et al: The EORTC core quality of life questionnaire (QLQ-C30): Validity and reliability when analysed with patients treated with palliative radiotherapy. Eur J Cancer 31A:2260-2263, 1995 11. Radbruch L, Elsner F, Trottenberg P, et al: Clinical Practice Guidelines on Cancer Cachexia in Advanced Cancer Patients. 2010. http://www.epcrc.org/ guidelines.php?p⫽cachexia
DOI: 10.1200/JCO.2014.60.6475; published online ahead of print at www.jco.org on March 9, 2015
■ ■ ■
Journal of Clinical Oncology, Vol 33, No 13 (May 1), 2015: pp 1513
© 2015 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on June 25, 2016. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
1513
Correspondence
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Reply to A. Molfino et al The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Ørnulf Paulsen No relationship to disclose
Pål Klepstad No relationship to disclose
Nina Aass No relationship to disclose
Stein Kaasa No relationship to disclose
© 2015 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Downloaded from jco.ascopubs.org on June 25, 2016. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
