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Original article
A retrospective analysis of the factors associated with hypercalcaemia in patients with advanced cancer C.-Y. WU, MD, Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung, C.-J. HUANG, MD, PHD, Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Y.-W. CHIU, MD, MS, Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, C.-T. HUANG, MD, Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung, & H.-Y. CHUANG, MD, MPH, SCD, Department of Community Medicine, Kaohsiung Medical University Hospital, Kaohsiung, and Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan WU C.-Y., HUANG C.-J., CHIU Y.-W., HUANG C.-T. & CHUANG H.-Y. (2014) European Journal of Cancer Care 23, 695–700 A retrospective analysis of the factors associated with hypercalcaemia in patients with advanced cancer Hypercalcaemia, a common complication of advanced cancer, causes multiple clinical symptoms, deteriorates patients’ quality of life, and is associated with poor prognoses. This study aimed to identify the factors that may be associated with hypercalcaemia in advanced cancer by retrospectively reviewing the medical records of patients (n = 404) admitted to the palliative ward of the Kaohsiung Medical University Hospital, Taiwan, from 2006 to 2008. Patients’ demographics, clinical data and symptoms were recorded. Seventy-nine of 404 patients had hypercalcaemia (19.6%), predominant in cases of head-and-neck cancer and haematological malignancies (P < 0.05), but not in those of bone metastases. Hypercalcaemia was associated with consciousness disturbances and leucocytosis (P < 0.05). We recommend that ionised (corrected) calcium levels be monitored clinically in patients with advanced cancer especially when consciousness disturbances are noted, or when head-and-neck or haematological malignancies are present. Testing of free calcium levels is also recommended in patients with leucocytosis.
Keywords: hypercalcaemia, advanced cancer, head-and-neck cancer, leucocytosis.
INTRODUCTION Hypercalcaemia is a common complication of advanced cancer (Muggia 1990; Theriault 1993; Stewart 2005) such that up to 30% of patients with advanced cancer are diagnosed with hypercalcaemia (Lamy et al. 2001; Stewart 2005; Shibata 2008; Chapireau et al. 2010). Hypercalcaemia leads to poor prognoses and is often life-threatening.
Correspondence address: Hung-Yi Chuang, MD, MPH, ScD, Department of Community Medicine, Kaohsiung Medical University Hospital and Department of Public Health, Kaohsiung Medical University 100 ShihChuan 1st Road, Kaohsiung 80708, Taiwan (e-mail: [email protected]).
Accepted 11 November 2013 DOI: 10.1111/ecc.12161 European Journal of Cancer Care, 2014, 23, 695–700
© 2013 John Wiley & Sons Ltd
Survival times range from 1 to 6 months in hypercalcaemic cancer patients (Ralston et al. 1990; Penel et al. 2005; Alsirafy et al. 2009). It has been reported that patients with breast cancer, multiple myeloma, lymphoma, and lung cancer are likely to develop hypercalcaemia (Burt & Brennan 1980; Muggia 1990). Hypercalcaemia-associated clinical symptoms include polyuria, polydipsia, dehydration, anorexia, nausea, constipation, weakness, confusion and delirium (Ralston et al. 1990; Lamy et al. 2001; Iwase et al. 2003; Inzucchi 2004). The higher the serum levels of ionised (corrected) calcium, the more intense the symptoms (Inzucchi 2004; Bradley & Hoskin 2006). These symptoms lead to poor quality of life in patients with advanced cancer. Management of hypercalcaemia, especially with bisphosphonate administration, can relieve patients’ symptoms and
WU ET AL.
improve their quality of life (Ralston et al. 1990; Lamy et al. 2001; Saunders et al. 2004). Paraneoplastic syndrome is a disease manifesting with a collection of symptoms that result from the presence of cancer(s) in some patients and leads to high morbidity and possibly mortality. Among paraneoplastic syndromes, hypercalcaemia–leucocytosis syndrome occurs less frequently than hypercalcaemia or leucocytosis alone, and if present, confers poor prognosis (Yoneda et al. 1991; Hiraki et al. 2004; Chapireau et al. 2010). However, the relationship between advanced cancer and paraneoplastic syndrome has not been well-studied. Therefore, we investigated the prevalence of hypercalcaemia in patients with advanced cancer and assessed associated clinical conditions, which may cause poor quality of life. The treatment strategy is to detect and manage hypercalcaemia as early as possible and to provide high-quality care for patients with advanced cancer.
represents functional calcium levels in vivo than does total serum calcium (Saunders et al. 2004).
PATIENTS AND METHODS
RESULTS
Patients and data collection
Of the 404 patients, 79 (19.6%) had hypercalcaemia. Demographic characteristics of the two patient groups are shown in Table 1. The difference in average patient age between the two groups was not statistically significant (61.9 ± 13.1 and 58.9 ± 13.4 years respectively). Further, 41.5% and 26.6% of patients were female in the nonhypercalcaemic and hypercalcaemic groups respectively. The primary cancer diagnoses of terminal cancer patients are shown in Table 1. The prevalence of headand-neck cancer and haematology malignancy cases were significantly different between the two groups. Head-andneck cancers predominanted in the hypercalcaemic group (P < 0.001). The two groups had similar matastatic conditions; however, the number of bone and brain metastases were higher in the non-hypercalcaemic group than in the hypercalcaemic group (P < 0.05). Paraneoplastic symptoms in the terminal patients are presented in Table 2. Most of the symptoms were not significantly different between the two groups. Abdominal fullness occurred more frequently in the nonhypercalcaemic group (P < 0.05). In contrast, the proportion of cases with consciousness disturbances (or unconsciousness) and fungating tumour wounds were significantly higher in the hypercalcaemic group (P < 0.05). Patients’ laboratory results were mostly similar between the two groups (Table 3). However, alanine transaminase was higher in the non-hypercalcaemic group (P = 0.021), whereas white blood cell counts and haemoglobin were significantly higher in the hypercalcaemic group (P < 0.001).
We reviewed retrospectively the medical records of patients with advanced cancer admitted to the palliativecare ward of the Kaohsiung Medical University Hospital, Taiwan, from January 2006 to December 2008. Our study was approved by our institutional review board. Age, sex, primary cancer diagnosis and metastatic conditions diagnosed by computed tomography, bone scan, sonography and magnetic resonance imaging, were documented. Paraneoplastic symptoms, including lethargy, anorexia, abdominal fullness, oedema, infection, breakthrough pain, ascites, consciousness disturbances (or unconsciousness), fungating tumour wounds, fever, bleeding, severe cough, insomnia and dizziness, were documented. The laboratory data at patient admittance included white blood cell counts, platelet counts, C-reactive protein, haemoglobin, aspartate transaminase, alanine transaminase, creatinine, sodium, potassium, ammonia, ionised (corrected) calcium, prothrombin time (normalised international ratio) and albumin.
Patients’ grouping Patients were classified into two groups according to presence or absence of hypercalcaemia. We used an ionised (corrected) calcium level of >5.5 mg/dL to indicate hypercalcaemia according to laboratory criteria (4.0–5.5 mg/dL or 1.0–1.3 mmol/L) established in the Kaohsiung Medical University Hospital. Ionised (corrected) calcium better 696
Statistical analysis Descriptive analyses were used to assess the differences between the demographic characteristics, paraneoplastic symptoms and blood parameters in the hypercalcaemic or non-hypercalcaemic group. Logistic regression analysis was used to assess associations between the clinical factors and hypercalcaemia. We used 14 variables, which differed significantly by the univariate analyses for the full analysis. Subsequently, a stepwise method was used to reduce the number of variables. Finally, in addition to the stepwise model, we included age, sex and bone metastases to perform our final analysis. The SPSS statistical package was used. A P-value of
Original article
A retrospective analysis of the factors associated with hypercalcaemia in patients with advanced cancer C.-Y. WU, MD, Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung, C.-J. HUANG, MD, PHD, Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Y.-W. CHIU, MD, MS, Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, C.-T. HUANG, MD, Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung, & H.-Y. CHUANG, MD, MPH, SCD, Department of Community Medicine, Kaohsiung Medical University Hospital, Kaohsiung, and Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan WU C.-Y., HUANG C.-J., CHIU Y.-W., HUANG C.-T. & CHUANG H.-Y. (2014) European Journal of Cancer Care 23, 695–700 A retrospective analysis of the factors associated with hypercalcaemia in patients with advanced cancer Hypercalcaemia, a common complication of advanced cancer, causes multiple clinical symptoms, deteriorates patients’ quality of life, and is associated with poor prognoses. This study aimed to identify the factors that may be associated with hypercalcaemia in advanced cancer by retrospectively reviewing the medical records of patients (n = 404) admitted to the palliative ward of the Kaohsiung Medical University Hospital, Taiwan, from 2006 to 2008. Patients’ demographics, clinical data and symptoms were recorded. Seventy-nine of 404 patients had hypercalcaemia (19.6%), predominant in cases of head-and-neck cancer and haematological malignancies (P < 0.05), but not in those of bone metastases. Hypercalcaemia was associated with consciousness disturbances and leucocytosis (P < 0.05). We recommend that ionised (corrected) calcium levels be monitored clinically in patients with advanced cancer especially when consciousness disturbances are noted, or when head-and-neck or haematological malignancies are present. Testing of free calcium levels is also recommended in patients with leucocytosis.
Keywords: hypercalcaemia, advanced cancer, head-and-neck cancer, leucocytosis.
INTRODUCTION Hypercalcaemia is a common complication of advanced cancer (Muggia 1990; Theriault 1993; Stewart 2005) such that up to 30% of patients with advanced cancer are diagnosed with hypercalcaemia (Lamy et al. 2001; Stewart 2005; Shibata 2008; Chapireau et al. 2010). Hypercalcaemia leads to poor prognoses and is often life-threatening.
Correspondence address: Hung-Yi Chuang, MD, MPH, ScD, Department of Community Medicine, Kaohsiung Medical University Hospital and Department of Public Health, Kaohsiung Medical University 100 ShihChuan 1st Road, Kaohsiung 80708, Taiwan (e-mail: [email protected]).
Accepted 11 November 2013 DOI: 10.1111/ecc.12161 European Journal of Cancer Care, 2014, 23, 695–700
© 2013 John Wiley & Sons Ltd
Survival times range from 1 to 6 months in hypercalcaemic cancer patients (Ralston et al. 1990; Penel et al. 2005; Alsirafy et al. 2009). It has been reported that patients with breast cancer, multiple myeloma, lymphoma, and lung cancer are likely to develop hypercalcaemia (Burt & Brennan 1980; Muggia 1990). Hypercalcaemia-associated clinical symptoms include polyuria, polydipsia, dehydration, anorexia, nausea, constipation, weakness, confusion and delirium (Ralston et al. 1990; Lamy et al. 2001; Iwase et al. 2003; Inzucchi 2004). The higher the serum levels of ionised (corrected) calcium, the more intense the symptoms (Inzucchi 2004; Bradley & Hoskin 2006). These symptoms lead to poor quality of life in patients with advanced cancer. Management of hypercalcaemia, especially with bisphosphonate administration, can relieve patients’ symptoms and
WU ET AL.
improve their quality of life (Ralston et al. 1990; Lamy et al. 2001; Saunders et al. 2004). Paraneoplastic syndrome is a disease manifesting with a collection of symptoms that result from the presence of cancer(s) in some patients and leads to high morbidity and possibly mortality. Among paraneoplastic syndromes, hypercalcaemia–leucocytosis syndrome occurs less frequently than hypercalcaemia or leucocytosis alone, and if present, confers poor prognosis (Yoneda et al. 1991; Hiraki et al. 2004; Chapireau et al. 2010). However, the relationship between advanced cancer and paraneoplastic syndrome has not been well-studied. Therefore, we investigated the prevalence of hypercalcaemia in patients with advanced cancer and assessed associated clinical conditions, which may cause poor quality of life. The treatment strategy is to detect and manage hypercalcaemia as early as possible and to provide high-quality care for patients with advanced cancer.
represents functional calcium levels in vivo than does total serum calcium (Saunders et al. 2004).
PATIENTS AND METHODS
RESULTS
Patients and data collection
Of the 404 patients, 79 (19.6%) had hypercalcaemia. Demographic characteristics of the two patient groups are shown in Table 1. The difference in average patient age between the two groups was not statistically significant (61.9 ± 13.1 and 58.9 ± 13.4 years respectively). Further, 41.5% and 26.6% of patients were female in the nonhypercalcaemic and hypercalcaemic groups respectively. The primary cancer diagnoses of terminal cancer patients are shown in Table 1. The prevalence of headand-neck cancer and haematology malignancy cases were significantly different between the two groups. Head-andneck cancers predominanted in the hypercalcaemic group (P < 0.001). The two groups had similar matastatic conditions; however, the number of bone and brain metastases were higher in the non-hypercalcaemic group than in the hypercalcaemic group (P < 0.05). Paraneoplastic symptoms in the terminal patients are presented in Table 2. Most of the symptoms were not significantly different between the two groups. Abdominal fullness occurred more frequently in the nonhypercalcaemic group (P < 0.05). In contrast, the proportion of cases with consciousness disturbances (or unconsciousness) and fungating tumour wounds were significantly higher in the hypercalcaemic group (P < 0.05). Patients’ laboratory results were mostly similar between the two groups (Table 3). However, alanine transaminase was higher in the non-hypercalcaemic group (P = 0.021), whereas white blood cell counts and haemoglobin were significantly higher in the hypercalcaemic group (P < 0.001).
We reviewed retrospectively the medical records of patients with advanced cancer admitted to the palliativecare ward of the Kaohsiung Medical University Hospital, Taiwan, from January 2006 to December 2008. Our study was approved by our institutional review board. Age, sex, primary cancer diagnosis and metastatic conditions diagnosed by computed tomography, bone scan, sonography and magnetic resonance imaging, were documented. Paraneoplastic symptoms, including lethargy, anorexia, abdominal fullness, oedema, infection, breakthrough pain, ascites, consciousness disturbances (or unconsciousness), fungating tumour wounds, fever, bleeding, severe cough, insomnia and dizziness, were documented. The laboratory data at patient admittance included white blood cell counts, platelet counts, C-reactive protein, haemoglobin, aspartate transaminase, alanine transaminase, creatinine, sodium, potassium, ammonia, ionised (corrected) calcium, prothrombin time (normalised international ratio) and albumin.
Patients’ grouping Patients were classified into two groups according to presence or absence of hypercalcaemia. We used an ionised (corrected) calcium level of >5.5 mg/dL to indicate hypercalcaemia according to laboratory criteria (4.0–5.5 mg/dL or 1.0–1.3 mmol/L) established in the Kaohsiung Medical University Hospital. Ionised (corrected) calcium better 696
Statistical analysis Descriptive analyses were used to assess the differences between the demographic characteristics, paraneoplastic symptoms and blood parameters in the hypercalcaemic or non-hypercalcaemic group. Logistic regression analysis was used to assess associations between the clinical factors and hypercalcaemia. We used 14 variables, which differed significantly by the univariate analyses for the full analysis. Subsequently, a stepwise method was used to reduce the number of variables. Finally, in addition to the stepwise model, we included age, sex and bone metastases to perform our final analysis. The SPSS statistical package was used. A P-value of
