Support Care Cancer (2015) 23:177–183 DOI 10.1007/s00520-014-2355-4

ORIGINAL ARTICLE

Physicians’ attitude toward recurrent hypercalcemia in terminally ill cancer patients Akira Shimada & Ichiro Mori & Isseki Maeda & Hidekazu Watanabe & Nobutaka Kikuchi & Hansheng Ding & Tatsuya Morita

Received: 3 February 2014 / Accepted: 14 July 2014 / Published online: 22 July 2014 # Springer-Verlag Berlin Heidelberg 2014

Abstract Background There is no consensus regarding whether cancerinduced hypercalcemia should be treated up until the patient’s death. The primary aim of this study was to clarify physicians’ attitude toward treating recurrent hypercalcemia in terminally ill cancer patients and associated factors.

A. Shimada Tohoku University Hospital Palliative Care Center, Seiryo-cho 1-1, Aoba, Sendai, Miyagi 980-8575, Japan e-mail: [email protected] I. Mori Gratia Hospital Hospice, 6-14-1 Aomadaninishi, Mino, Osaka 562-8567, Japan e-mail: [email protected] I. Maeda Department of Palliative Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan e-mail: [email protected] H. Watanabe : N. Kikuchi Division of Palliative Medicine, Tohoku University Graduate School of Medicine, Seiryo-cho 2-1, Aoba, Sendai, Miyagi 980-8575, Japan H. Watanabe e-mail: [email protected] N. Kikuchi e-mail: [email protected] H. Ding Department of Health Administration and Policy, Tohoku University Graduate School of Medicine, Seiryo-cho 2-1, Aoba, Sendai, Miyagi 980-8575, Japan e-mail: [email protected] T. Morita (*) Department of Palliative and Supportive Care, Palliative Care Team, and Seirei Hospice, Seirei Mikatahara General Hospital, 3453 Mikatahara-cho, Kita-ku, Hamamatsu, Shizuoka 433-8558, Japan e-mail: [email protected]

Methods A nationwide, cross-sectional survey was performed involving 757 physicians of the Japanese Society for Palliative Medicine. Physicians’ attitude toward treating hypercalcemia in terminally ill patients was assessed based on the response to the question: do you agree that you provide medical treatment for recurrent hypercalcemia up until a patient’s death? As the potential determinants of physicians’ attitudes, we examined their characteristics, beliefs about hypercalcemia, and beliefs about a good death. Results We obtained a total of 380 (50.2 %) analyzable responses. A total of 163 physicians (43 %) agreed that hypercalcemia should be treated up until the patient’s death, while the remaining 217 physicians (57 %) disagreed. The independent determinants of the attitude included the following: physicians’ specialty, belief that hypercalcemia treatment improves pain, belief that hypercalcemia treatment improves nausea, belief that hypercalcemia treatment improves quality of life, belief that hypercalcemia treatment prolongs life, belief that the effect of hypercalcemia treatment reduces gradually, belief that death with hypercalcemia is less distressing, and the perception that being mentally clear is important for a good death. Conclusion Japanese physicians had different attitudes toward treating hypercalcemia in terminally ill patients. Physicians’ beliefs about the efficacy of medical treatment for hypercalcemia markedly influenced their attitudes. Clarifying evidence on the effect of hypercalcemia treatment on patients’ symptoms and prognoses is strongly encouraged. Keywords Hypercalcemia . Attitude . Physician . Survey . Palliative care

Introduction The incidence of malignant hypercalcemia varied between 10 and 20 % in advanced cancer [1–4]. It is most commonly seen

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in patients with breast, lung, and kidney cancers and in multiple myeloma. Many patients respond to bisphosphonate treatment, while the most typical side effects of bisphosphonates are fever and flu-like symptoms. Time to relapse is approximately 2– 4 weeks, however, when the treatment should be repeated and the subsequent episodes of hypercalcemia seem to become increasingly difficult to treat. Hypercalcemia causes a variety of distressing symptoms, such as fatigue, nausea and vomiting, constipation, delirium, dehydration, and renal failure, and thus should be treated if possible. For example, some empirical studies identified hypercalcemia as a one of the reversible causes of delirium in advanced cancer patients [5, 6]. Initial response to medical treatment is 70 % or more, resulting in a decreased level of serum calcium values and improved patient quality of life [1–4]. However, hypercalcemia usually relapses after the initial remission, and the main issue of hypercalcemia in terminally ill cancer patients is not the initial treatment but how physicians manage hypercalcemia when the patient develops hypercalcemia again [7–12]. Some anecdotal reviews state that a physician usually can treat hypercalcemia as a medical disorder, but, in some cases, an untreated condition may allow a terminally ill patient to die without pain and distressing symptoms; physician may use the first episode of hypercalcemia as an opportunity to talk to the patient and family about the prognosis and end-of-life options [7–12]. To date, there has been no international consensus about whether or not physicians should manage recurrent hypercalcemia in terminally ill cancer patients. Clarifying physicians’ attitude toward recurrent hypercalcemia in terminally ill cancer patients and their associated factors is of value to help understand the current situation and develop guidelines to minimize the risks of overtreatment and undertreatment. Many studies confirmed that physicians’ specialty, clinical experience, and their own value markedly influence their endof-life practices [13–16]. Nonetheless, no empirical studies have been performed on how to treat hypercalcemia in terminally ill patients. Therefore, the primary aim of this study was to clarify physicians’ attitudes toward recurrent hypercalcemia in terminally ill cancer patients and associated factors.

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Subjects Potential participants were recruited from the member list of the Japanese Society for Palliative Medicine. The Japanese Society for Palliative Medicine is a multidisciplinary association, consisting of palliative medicine specialists, oncologists, internists, and surgeons with an interest in palliative care. A total of 757 physicians, whose specialty involved treating hypercalcemia in daily practice (i.e., internal medicine, surgery, oncology, and palliative medicine), were requested to complete and return the questionnaire. Physicians whose specialty was thought to involve treating hypercalcemia rarely (such as emergency medicine, psychiatry, pathology, and public health) were excluded. Questionnaire Due to a lack of validated instruments, we developed the questionnaire through discussions and reviewing literature with reference to our previous similar studies [7–12, 15, 16]. Face validity was confirmed in a pilot test. As a primary endpoint, we used one question: do you agree that you provide medical treatment for hypercalcemia up until a patient’s death, which was assessed on a six-point Likert-type scale [1 (strongly disagree) to 6 (strongly agree)]. Physicians who (dis)agreed were defined as those who chose any of “slightly (dis)agree,” “(dis)agree,” or “strongly (dis)agree.” As the potential determinants of physicians’ attitudes, we examined three categories: (1) physicians’ characteristics, (2) physicians’ beliefs about hypercalcemia, and (3) physicians’ beliefs about a good death. Their characteristics included sex, years of clinical practice, specialty, experience of anticancer treatment, and practice settings. The respondents were asked to rate the degree of agreement with 12 brief statements about hypercalcemia treatment on a six-point Likert-type scale from 1 (strongly disagree) to 6 (strongly agree), such as “hypercalcemia treatment improves pain” and “death in hypercalcemia is less distressing” (Table 2). Moreover, they were required to rate the degree of agreement with “no distress,” “being mentally clear,” “hope is maintained,” and “natural death and minimum medical interventions” being important for a patient’s good death [17, 18]. These items were selected from the previous good death studies [17, 18] and examined on a sixpoint Likert-type scale from 1 (not important at all) to 6 (vital).

Subjects and methods

Statistical analyses

This study was designed as a nationwide, cross-sectional survey, in which a self-reported questionnaire was mailed to eligible physicians in 2004. The second questionnaire was mailed to physicians who had not returned the first one. Scientific and ethical validity was approved by the Institutional Review Board of Tohoku University.

We defined physicians who had a positive attitude toward treating hypercalcemia in terminally ill patients as those who responded slightly agree, agree, or strongly agree to the statement “(the respondent) provides medical treatment for hypercalcemia until a patient’s death.” The physicians who responded slightly disagree, disagree, or strongly disagree to

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that statement were defined as those who had a negative attitude. To explore the differences between physicians with positive and negative attitudes, the physicians’ background (sex, years of clinical practice, specialty, and experience of anticancer treatment), 12 belief statements, and perceptions on the four good death items were compared using the χ2 test or Student’s t test, where appropriate. The P value for significance was defined as 0.002 (0.05/23) using Bonferroni correction. For multivariate analyses, factors significantly different between groups were entered into a logistic regression model using physicians with negative attitude as independent variables. To explore the physicians’ attitudes according to specialty, we additionally compared the main outcome, i.e., the response to “do you agree that you provide medical treatment for hypercalcemia up until a patient’s death on a six-point Likert-type scale, among different specialties using ANOVA. For analyses, specialties were grouped into four categories: palliative medicine (palliative care, home hospice practice, or pain medicine), surgery (general surgery, thoracic surgery, urology, gynecology, orthopedics, or otorhinolaryngology), internal medicine (general internal medicine, gastroenterology, respiratory medicine, or neurology), and oncology (medical oncology, radiation oncology, hematology, and breast medicine). Post hoc tests were performed using Scheffe’s test. For this exploratory analysis, the P value necessary for significance was defined as 0.05. All analyses were performed using the Statistical Package for the Social Sciences version 13.

Results We obtained a total of 380 (50.2 %) analyzable responses from 757 physicians. Background characteristics are summarized in Table 1. Physicians had an experience of treating hypercalcemia with a mean of a total of 21 patients during their experience as a physician (median, 10; range, 1 to 250); palliative care specialists and oncologists experienced significantly more patients than internal medicine and surgeons (median, 20 vs. 20 vs. 10 vs. 5, respectively). In the most recent year, the responding physicians treated an average of 3.9 patients with hypercalcemia (median, 2; range, 0 to 100); palliative care specialists experienced significantly more patients than oncologists, internal medicine, and surgeons (median, 4 vs. 2 vs. 1.5 vs. 1, respectively). Attitudes toward recurrent hypercalcemia in terminally ill cancer patients Overall, 163 physicians (43 %) slightly agreed, agreed, or strongly agreed with “treating hypercalcemia up until a

179 Table 1 Background of respondents (n=380) No. Sex (male) Mean clinical experience (years, standard deviation) Specialty Palliative medicine Surgery Internal medicine Oncology Experience of anticancer treatments Yes No Practice settings General hospitals Palliative care units/inpatient hospices Cancer centers Medical clinics

Percent

343 90 21 (8.3) 143 96 74 65

38 25 20 17

350 28

95 7.4

169 91 85 29

45 24 22 7.6

patients’ death,” while the remaining 217 physicians (57 %) slightly disagreed, disagreed, or strongly disagreed. There was a significant difference in the main outcome score among specialties (Fig. 1, P=0.048). Surgeons and oncologists showed a significantly more positive attitude toward treating hypercalcemia. Determinants of physicians’ attitude toward recurrent hypercalcemia in terminally ill cancer patients As shown in Table 2, physicians with a positive attitude toward treating hypercalcemia in terminally ill patients were significantly more likely to believe that hypercalcemia treatment improves pain, improves fatigue, improves the quality of life, and prolongs life and that being mentally clear is

Fig. 1 Difference in the attitude toward treating hypercalcemia in terminally ill patients among specialties. Mean score with 95 % confidence intervals for the response to the question: do you agree that you provide medical treatment for hypercalcemia up until a patient’s death, on a sixpoint Likert-type scale from 1 (strongly disagree) to 6 (strongly agree)

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Table 2 Determinants of physicians’ attitude toward treating hypercalcemia in terminally ill patients Factors Characteristics Sex (male) Clinical experience (years, standard deviation) Specialty Palliative medicine Surgery Internal medicine Oncology Experience of anticancer treatment Beliefsa Belief that hypercalcemia treatment improves pain Belief that hypercalcemia treatment improves nausea Belief that hypercalcemia treatment improves constipation Belief that hypercalcemia treatment improves consciousness Belief that hypercalcemia treatment improves delirium Belief that hypercalcemia treatment improves fatigue Belief that hypercalcemia treatment improves quality of life Belief that hypercalcemia treatment prolongs life Belief that effect of hypercalcemia treatment reduces gradually Belief that effect of hypercalcemia treatment is unpredictable Belief that death with hypercalcemia is less distressing Belief that bisphosphonate is expensive Perceived importance for good deathb No distress Being mentally clear Hope maintained Natural death and minimum medical interventions

Number (%)

Positive (n=163)

Negative (n=217)

P

149 (91 %) 22 (7.9)

194 (90 %) 21 (8.7)

0.60 0.41

43 (26 %) 51 (31 %) 32 (20 %) 35 (22 %) 151 (93 %)

100 (46 %) 45 (21 %) 42 (19 %) 30 (14 %) 199 (92 %)

0.001

299 (79) 298 (78) 190 (50) 342 (90) 317 (83) 288 (76) 346 (91)

4.4 (1.0) 4.5 (0.9) 3.7 (0.9) 4.9 (0.9) 4.6 (0.9) 4.3 (0.9) 4.7 (0.8)

4.1 (0.9) 4.2 (0.9) 3.6 (0.9) 4.7 (0.8) 4.4 (0.9) 4.1 (0.8) 4.3 (0.8)

0.001 0.010 0.15 0.070 0.085 0.002

Physicians' attitude toward recurrent hypercalcemia in terminally ill cancer patients.

There is no consensus regarding whether cancer-induced hypercalcemia should be treated up until the patient's death. The primary aim of this study was...
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