When Expectations Predict Experience: The Influence of Psychological Factors on Chemotherapy Toxicities

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1 1036 Journal of Pain and Symptom Management Vol. 43 No. 6 June 2012 Original Article When Expectations Predict Experience: The Influence of Psychological Factors on Chemotherapy Toxicities Hayley S. Whitford, PhD, and Ian N. Olver, MD, PhD, FRACP Cancer Council Australia (H.S.W., I.N.O.), Sydney, New South Wales, and School of Psychology (H.S.W.), The University of Adelaide, Adelaide, South Australia, Australia Abstract Context. Patients with cancer undergoing similar treatments experience variable severity and frequency of side effects not adequately explained by pharmacological mechanisms, suggesting psychological influence. Objectives. First, this study aimed to further examine the relationship between patients expectations of multiple chemotherapy-related toxicities and experiences. Second, this study aimed to explore the impact of anxiety and cancer coping styles to aid in informing interventions to lessen such expectations. Methods. A total of 59 eligible, consenting patients with cancer rated their expectations of 20 chemotherapy toxicities on 100-point linear analogue selfassessment indicators before treatment and completed the Spielberger State Anxiety Inventory and the Mental Adjustment to Cancer scale. Patients then rated their experience of side effects after one chemotherapy session. Results. Regressions controlling primary treating nurse influence and patient performance status showed toxicity experience was significantly predicted by patient expectations of mood changes, bleeding, skin itchiness, hair loss, feeling tired, and sleep disturbance (b ¼ 0.30e0.55). Anxiety was significantly related to expectations of nervousness and mood changes; the coping style Fighting Spirit showed no significant associations, whereas conversely, Anxious Preoccupation showed some degree of association with all 20 toxicities (r ¼ 0.11e0.34). Conclusion. Findings support the growing contention that patient expectations influence experience, negatively impacting quality of life. As it is unethical to withhold treatment information, research into screening for at-risk patients and offering brief interventions to minimize Anxious Preoccupation could be one way to reduce overall side effect burden, perhaps in the case of many medical interventions. J Pain Symptom Manage 2012;43:1036e1050. Ó 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Address correspondence to: Hayley S. Whitford, PhD, Cancer Council Australia, c/o School of Psychology, The University of Adelaide, North Terrace, Ó 2012 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All rights reserved. Adelaide, South Australia 5005, Australia. hayley.whitford@cancer.org.au Accepted for publication: June 28, /$ - see front matter doi: /j.jpainsymman

2 Vol. 43 No. 6 June 2012 Expectations Predict Experience 1037 Key Words Cancer, oncology, chemotherapy, toxicities, expectations, anxiety, coping styles Introduction Individual patients with mixed cancer diagnoses who undergo chemotherapy experience varying frequency and severity of side effects that cannot be adequately explained by pharmacological differences alone. Thus, research has examined the role of psychological determinants, specifically patient expectations, and how they may impact an individual s experience of chemotherapy-related toxicities. Perhaps the most relevant theory of expectations applicable to medical intervention outcomes is Kirsch s 1 response expectancy theory. Response expectancies, unlike other expectancies described in various learning theories, refer to automatic nonvolitional responses that can impact experience, behavior, and physiological function. In essence, Kirsch 1 suggested that what one experiences depends partly on what one expects to experience, a process suggested to underpin the placebo effect, hypnosis, fear reduction, and pharmacological agents. Kirsch 1 hypothesized that response expectancies are not mediated by other constructs (i.e., psychological variables) and are sufficient to cause such nonvolitional outcomes while being self-confirming (although automatic). 2 A recent meta-analysis of 14 studies including 1445 patients aimed to determine whether patient expectations contributed to the experience of side effects as a consequence of cancer treatments, 3 including assessments of multiple side effects and various interventions. Findings suggested that, on average, associations between expectations and experience were indeed significant, showing a moderate association (r ¼ 0.36, P < 0.001). Comparisons between the toxicities of pain, fatigue, nausea, and vomiting found similar magnitudes of association. Only pain appeared to show a significantly stronger association between expectation and experience compared with vomiting. The authors concluded that results supported the contribution of patient expectations to cancer treatment-related side effects and future research should be aimed at altering such expectations to improve patient quality of life. We previously investigated the association between 87 chemotherapy-naive patients expectations and their experience of 20 common side effects. 4 This study was an attempt to extend on previous work by Cassileth et al. 5 by exploring a greater number of toxicities using more sensitive assessments. Results indicated that, even after controlling other influences (primary treating nurse expectations and patient performance status), most patient expectations of side effects were shown to significantly influence experience to some degree, especially for the more subjective or ambiguous toxicities. Thus, we concluded that the emphasis on personal autonomy (such as obtaining fully informed consent before treatment) may in some cases aid in setting up negative expectations that may translate into adverse experiences to the detriment of the patient. The present study aimed to further examine the relationship between patients expectations and their experience of chemotherapyrelated toxicities using the same successful methods as previously used. Furthermore, we aimed to add to our knowledge by investigating the influence of other psychological factors on expectations, as previous research showed mixed evidence regarding the impact of anxiety, 5e7 and no other studies to our knowledge had investigated the impact of multiple coping styles of patients. As Montgomery and Bovbjerg 8 discovered in their assessment of 80 breast cancer patients receiving adjuvant chemotherapy, although trait anxiety appeared to be a stronger predictor of pretreatment expectations than a measure of distress, neither contributed to multivariate models. Thus, the search for such predictors needs to be wider. Understanding adjustment to cancer may aid in explaining the placebo side effect (when optimistic styles lead to a negative outcome) and the nocebo effect (when negative or pessimistic expectations lead to positive or unexpected outcomes). 4,9

3 1038 Whitford and Olver Vol. 43 No. 6 June 2012 Methods Participants Chemotherapy-naive patients with appointments in the medical oncology department at the Royal Adelaide Hospital (RAH) Cancer Center, Australia, were approached by treating clinicians or data managers between November 2006 and July 2007, for trial participation. Eligibility criteria included having a cancer diagnosis, being chemotherapy naive, being 18 years or older, the ability to read English, a prognosis of more than six months, and the ability to consent. Patients with psychiatric or neurological illness, dementia, head injury, or substance abuse were excluded. Finally, patients were further checked to make sure they were not participating in other trials in the cancer center that could have interfered with the present study. This study was approved by the Ethics Committee of the RAH. A total of 59 participants were eligible and agreed to participate during this period. Of these 59 patients, 11 did not complete necessary items on questionnaires to run main regression analyses (one provided no Eastern Cooperative Oncology Group [ECOG] data and did not provide expectations data; three did not provide expectations data; seven did not provide experiences data at Time 2). Similarly, for three patients, primary treating nurses did not provide expectations data necessary for regression analyses. Thus, for main analyses, 45 cases provided some follow-up data, although not all 45 provided 100% data. For example, the lowest sample size for a regression model was n ¼ 39 for assessing problems with sex. Data Collection Eligible patients who provided written informed consent to the study were asked to fill in a short battery of self-report questionnaires before they commenced their initial chemotherapy session; this occurred after they had received all treatment information including the hospital s standard written information sheet describing their specific chemotherapy regimen and its unique combination of side effects, reflecting real procedure. Patients were later asked to complete one additional questionnaire about their experience of having side effects before they commenced their second chemotherapy session. This time frame was chosen in an attempt to rule out the influence of anticipatory side effects such as nausea and vomiting. State Anxiety. The Spielberger State Anxiety Inventory (SAI) forms part of the larger State-Trait Anxiety Inventory (STAI). 10 It is a 20-item, self-report questionnaire that aims to measure an individual s level of anxiety at the time of assessment. Participants rate the intensity of their feelings on a four-point frequency rating scale ranging from (1) not at all to (4) very much so. Higher scores indicate more intense, more frequent anxiety, and scores greater than 40 are suggestive of clinical levels of anxiety. 11 State anxiety is known to be highly correlated with an individual s trait (or dispositional) anxiety. For the present study, the reliability of the SAI was high (Cronbach s a ¼ 0.91). Cancer Coping Styles. The Mental Adjustment to Cancer (MAC) scale is used to assess current reactions to having cancer by asking patients to rate 40 short statements using four-point scales ranging from (1) definitely does not apply to me to (4) definitely applies to me. Scoring keys are provided with the scale to calculate subscale scores for five coping styles. 12 Reliability coefficients (Cronbach s as) calculated for the subscales in the present study were as follows: Fighting Spirit, 0.82; Helpless/Hopeless, 0.81; Anxious Preoccupation, 0.68; and Fatalistic, Internal reliability cannot be calculated for the subscale of Avoidance as it is one single item. Patient Expectations and Experience Questionnaires. Study-specific questionnaires assessing patient side effect expectations were administered prechemotherapy along with the SAI, MAC scale, and demographic questions. Using a list of 20 common chemotherapy-related toxicities, patients were asked to rate the expected severity of each toxicity on linear analogue selfassessment (LASA) indicators ranging from 0 (do not expect the side effect at all) to 100 (expect the worst possible severity of the side effect). These LASA scales for expectations were first published by Olver et al., 4 initially based on and extending the 16 side effects assessed by Cassileth et al. 5 in similar research.

4 Vol. 43 No. 6 June 2012 Expectations Predict Experience 1039 Patients experiences of the same 20 toxicities were assessed in the same manner before patients commenced their second course of treatment; this was approximately three to four weeks since their first day of chemotherapy. Demographic and Disease Characteristics. Some demographic, disease, and treatment information was collected from patients; other information was collected or verified through hospital records, including age, gender, marital status, educational level, usual occupation, nationality, English as a second language, time since diagnosis, type of cancer, ECOG performance status, 13 treatment and performance expectations, and perceptions of treatment information received. Nurse Expectations Questionnaire. The principal nurse involved in treating the patient was asked to rate the likelihood of toxicity experience for each patient based on previous knowledge and experience of specific chemotherapy regimens. Nurses did this by filling in an identical questionnaire as described for assessing patient expectations; specifically, they rated 20 common side effects on 100-point LASA scales, indicating the severity of the side effects they expected to see in patients given their individual treatment regimens, ranging from 0 (do not expect the side effect at all) to 100 (expect the worst possible severity of the side effect). Statistical Analysis Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 17.0 (SPSS, Inc., Chicago, IL). Descriptive statistics and frequencies were used to characterize the sample. Independent samples t-tests were used to explore differences between those that provided/did not provide followup (attrition). To assess the first research question, a series of hierarchical multiple regression analyses were used to determine which patient expectations of side effects predicted experience, controlling for patient performance status and primary treating nurses expectations. To assess the second research question, separate Pearson product-moment correlations were used to explore the associations between patient expectations, state anxiety, and cancer coping rather than adding these variables to regressions, as these explorations were new (not hypothesized) and would have further compromised the power of regression models. As the sample size compromised power for some analyses, in addition to reporting exact P-values, effect sizes are reported and discussed rather than simply relying on null hypothesis significance testing. Specifically, standardized regression coefficients (b) are reported for regression analyses. Correlation coefficients of 0.10, 0.30, and 0.50 represent small, moderate, and large effects, respectively. 14 Although multiple analyses can inflate Type 1 error, Perneger 15 suggests that Bonferroni adjustments are not essential when all analyses are hypothesized or predetermined. Data were collected until follow-up data collection was achieved for approximately 45 patients, using the ratio 1:15, representing one independent variable to 15 cases for primary (regression) analyses. 16 Results Data Screening Data were screened for missing values, normality, and outliers, and tested for additional assumptions related to multiple regression analyses (including multicollinearity and homoscadesticity of residuals). 10 There were 11 cases with less than three missing items for the SAI; therefore, according to manual specifications, these data were replaced with mean item scores to give as many total scores as possible. 10 Variables were not heavily skewed and transformations did not improve scores enough to warrant changing from raw scores that were easier to interpret. Attrition Analyses Attrition analyses were performed to determine whether there were any significant differences between those patients that provided follow-up data and those eight patients that dropped out of the study (on demographics, expectations, state anxiety, and cancer coping styles). Two moderate, significant differences were found between the two groups including expectations of hair loss, t(51) ¼ 2.15, P ¼ 0.04, 4 ¼ 0.29, where those that dropped out of the study (M ¼ 75.7, standard deviation

5 1040 Whitford and Olver Vol. 43 No. 6 June 2012 [SD] ¼ 21.5) showed higher expectations than those that provided follow-up data (M ¼ 45.7, SD ¼ 35.8); and expectations of mood changes, t(51) ¼ 2.19, P ¼ 0.03, 4 ¼ 0.29, where those that dropped out (M ¼ 51.4, SD ¼ 22.7) showed higher expectations than those that provided follow-up data (M ¼ 29.8, SD ¼ 24.6). Some other expectation scores were approaching significance and showed small-to-moderate differences between the groups, but all were in the same direction, showing that those who dropped out of the study had higher expectations of experiencing side effects during treatment, thus showing a degree of bias to caution when interpreting results. Participant Characteristics Table 1 outlines the demographic characteristics of the sample. In summary, the average age of patients was about 55 years, although ages ranged from 22 to 79 years as would be expected in a patient population receiving anticancer chemotherapy. Just over half of the participants were female, and more than half were married or in a de facto relationship Table 1 Demographic Characteristics of the Sample Characteristic N/n n (%) Age, years (mean, SD) (13.7); range 22e79 Gender (% female) (54.2) Marital status Married/de facto (58.6) Never married/single 11 (19.0) Separated/divorced 9 (15.5) Widowed 4 (6.9) Educational level Primary 57 6 (10.5) Secondary 37 (64.9) Tertiary 14 (24.6) Usual occupation Home duties (27.3) Blue collar/ 11 (20.0) tradesperson Professional 11 (20.0) Unskilled 5 (9.1) White collar 4 (7.3) Retired/pensioner 1 (1.8) Other 8 (14.5) Nationality Australian (71.4) British/European 14 (25.0) Asian 2 (3.6) English first language (% no) 58 3 (5.2) (living together). A quarter reported having a tertiary education, and usual occupations were mixed, but the highest single proportion reported home duties as their main occupation. Over 70% classified themselves as Australian, with about 5% reporting English as their second language. Table 2 reports the disease characteristics of the sample. Patients were, on average, close to one year since diagnosis, but the range of time since diagnosis was high. Diagnoses were mixed, with a majority reporting to have breast cancer, followed by gynecological cancers. A large majority of patients suggested they were either capable of normal activity or only showed some evidence of symptoms according to ECOG scores. About half expected a cure from their treatment and less than a quarter expected to maintain normal activity over the course of chemotherapy. Fifteen patients (28.3%) reported that they learned about new side effects that could be expected during chemotherapy after reading the consent form, with two patients suggesting Table 2 Disease Characteristics of the Sample Characteristic N/n n (%) Weeks since diagnosis (mean, SD) (134.4); range 0e780 Type of cancer Breast (20.3) Gynecological 8 (13.6) Lung 7 (11.9) Leukemia/lymphoma 7 (11.9) Colorectal 6 (10.2) Head and neck 6 (10.2) Hepatobiliary 4 (6.8) Urogenital 3 (5.1) Upper gastrointestinal 2 (3.4) Other/unknown primary 4 (6.8) ECOG Performance Status a (49.1) 1 22 (40.0) 2 4 (7.3) 3 2 (3.6) 4 0 (0.0) Expectation of treatment results Cure (50.0) Control 25 (46.3) Do not know 2 (3.7) Expect to maintain normal activity? Yes 100% (20.0) As much as possible 40 (72.7) No 4 (7.3) a ECOG is the Eastern Cooperative Oncology Group s standardized measure of a patient s performance status; 0 represents normal, 4 represents more than 50% waking time spent in bed. 7

6 Vol. 43 No. 6 June 2012 Expectations Predict Experience 1041 all of the toxicities or most of them were new to them. However, by the beginning of their second chemotherapy session, no patients reported experiencing any additional toxicities not already reported on the consent form. As can be seen in Table 3, a large majority of patients felt they had received the right amount of information, although a small group suggested they would have preferred more information. When patients were asked where they obtained most of their information about treatment, most said they had received it from their doctors, about half said it came from nurses, and almost a third mentioned books, magazines, and pamphlets. Less than 4% mentioned that most of their treatment information had come from the information sheet and consent form. These results are similar to those reported in other Australian studies. 17,18 Expectations vs. Experience of Chemotherapy Toxicities To test the degree that expectations of individual side effects contributed to the experience of those same toxicities, a series of hierarchical multiple regression analyses were conducted. In an attempt to control possible confounding influences, in the first step of each analysis, two variables were added, including patients ECOG performance scores and the primary treating nurse expectation of the patient having the side effect. Once these were controlled, the patients expectations were added to the model to predict the patients experience of each toxicity (Table 4). Table 3 Patient Perception of Treatment Information Received Information Questions N/n n (%) Amount of information received Too much 55 0 (0.0) Just right 46 (83.6) Too little 9 (16.4) Obtained most information from a Doctors (85.5) Nurses (52.7) Books/magazine/pamphlets (29.1) Internet (18.2) Family/friends 55 4 (6.8) Information sheet and consent form 55 2 (3.6) Television 55 1 (1.8) Videos 55 0 (0.0) a Multiple responses allowed. Results indicated that seven models were significant, suggesting that the three variables added to each of these models (ECOG scores, nurse expectations, and patient expectations) predicted a significant amount of variance on experience of these seven side effects, ranging from contributions of 15%e34% of the variance. These included, in order of predictive strength (lowest to highest): mood changes, diarrhea, bleeding, skin itchiness/scaling, hair loss, feeling tired, and sleep disturbance. In six of these cases, patient expectations were significant individual predictors, suggesting that, after controlling for performance status and nurse influence, expectations of having these side effects significantly influenced the patients experience of having these toxicities after the first course of chemotherapy. The only toxicity that did not uniquely contribute significant prediction to the overall model was diarrhea. The standardized regression coefficient (b) suggested the size of this contribution was small to moderate (0.18), a result that could have been significant perhaps if power was increased. Other models of note, where expectation contributions were verging on significance and beta values were moderate (suggesting moderate influence in the models), were for the side effects of changes in taste/appetite, problems with concentration, and problems with sex. In reference to the possible confounding variables added to all regression analyses, patient ECOG performance status scores significantly contributed only to the model for tiredness (b ¼ 0.35, P ¼ 0.01), whereas nurse expectations significantly contributed to four models, suggesting primary treating nurses had greater influence on patient expectations. These models included nausea (b ¼ 0.32, P ¼ 0.04), hair loss (b ¼ 0.35, P ¼ 0.03), diarrhea (b ¼ 0.38, P ¼ 0.02), and pain related to treatment (b ¼ 0.39, P ¼ 0.01). All of these contributions were moderate; thus, perhaps with increased power, more small-to-moderate associations also would have been evident. Anxiety and Coping Styles Table 5 shows the means and SDs for the standardized psychological measures assessed, including their comparison to normative data obtained from the literature. Overall, of the

7 1042 Whitford and Olver Vol. 43 No. 6 June 2012 Table 4 The Unique Contribution of Patients Expected Chemotherapy Toxicities on Experience of Those Toxicities Common Side Effects of Chemotherapy Full Model Contribution of Expectations n Adjusted R 2 F P R 2 change F change P b Feeling tired Change in taste/appetite Weight loss Nausea Vomiting Nervousness Constipation Diarrhea Sleep disturbance Skin itchiness/scaling Weakness Chills/fever Pain related to drug treatment Hair loss Nail changes Mood changes Sore mouth Bleeding Problems with concentration Problems with sex Adjusted R 2 ¼ variance accounted for by all independent variables (patients Eastern Cooperative Oncology Group scores, nurse expectations, and patient expectations); R 2 change ¼ unique variance contributed to the model by patient expectations of the specified toxicity; b ¼ standardized regression coefficient (beta). 58 patients who completed the SAI, a total of 27 patients (46.6%) could be classified as falling within the range of clinical anxiety (having scores > 40). The mean state anxiety score for the current sample was higher than the general population norm reported by Forsberg and Bj orvell, 19 which showed a similar norm to those reported for working adults for males (M ¼ 34.5, SD ¼ 10.3, n ¼ 382) and females (M ¼ 32.2, SD ¼ 8.7, n ¼ 382) in the STAI manual. 10 According to the MAC scale, scores for the coping style of Helpless/Hopeless were low, showing good adjustment. Scores for Anxious Preoccupation, Fatalistic, and Avoidance were moderate. Scores for the coping style of Fighting Spirit also were high, suggesting good adjustment. Overall, scores on the MAC were very similar to another sample of 999 newly diagnosed patients with mixed cancer diagnoses from the same cancer center (no more than 0.50 differences in mean scores); the largest discrepancy appeared to be that for the coping style Fatalism, where the current sample showed an increase (worsening) of 1.3 in the mean score. 20 Associations Between Expectations and Psychological Factors Table 6 shows further explorations into possible psychological influences on expectations by providing correlations with state anxiety and the five cancer coping styles assessed by Table 5 Means and SDs for State Anxiety and Cancer Coping Styles Anxiety and Coping Styles N/n Actual Range Current Sample, M (SD) Norms, a M (SD) State anxiety b 58 20e (10.9) 33.2 (9.6) Cancer coping styles c Fighting Spirit 52 26e (6.7) 51.7 (6.9) Helpless/Hopeless 54 6e (3.1) 9.5 (3.0) Anxious Preoccupation 54 9e (4.4) 22.0 (4.1) Fatalistic 50 8e (3.2) 18.4 (3.6) Avoidance 59 1e4 2.0 (1.0) 1.8 (0.9) a Norms for the State Anxiety Inventory (SAI) based on randomly selected sample of 180 (50% male) from the general Swedish population; 13 norms for the Mental Adjustment to Cancer (MAC) scale based on 999 patients newly diagnosed cancer patients with mixed diagnoses from the same cancer center (RAH). 14 b State anxiety as measured by the SAI. 4 c Cancer coping styles as measured by the MAC scale. 6

8 Vol. 43 No. 6 June 2012 Expectations Predict Experience 1043 Table 6 Correlations Among Patient Expectations of Chemotherapy Toxicities Before Treatment, State Anxiety, and Five Cancer Coping Styles Common Side Effects of Chemotherapy State Anxiety r (P) Fighting Spirit r (P) Helpless/ Hopeless r (P) Anxious Preoccupation r (P) Fatalistic r (P) Avoidance r (P) Feeling tired 0.05 (0.74) 0.16 (0.28) 0.11 (0.43) 0.33 (0.02) 0.23 (0.12) 0.18 (0.18) Change in taste/ 0.11 (0.45) 0.13 (0.38) 0.06 (0.67) 0.29 (0.05) 0.03 (0.87) 0.15 (0.26) appetite Weight loss 0.01 (0.97) 0.12 (0.43) 0.08 (0.60) 0.28 (0.05) 0.10 (0.50) 0.01 (0.96) Nausea 0.01 (0.96) 0.17 (0.25) 0.11 (0.46) 0.27 (0.05) 0.11 (0.47) 0.11 (0.43) Vomiting 0.01 (0.96) 0.10 (0.52) 0.16 (0.26) 0.30 (0.04) 0.09 (0.53) 0.16 (0.24) Nervousness 0.41 (0.002) 0.17 (0.26) 0.24 (0.09) 0.30 (0.04) 0.03 (0.84) 0.03 (0.84) Constipation 0.08 (0.57) 0.07 (0.62) 0.02 (0.87) 0.28 (0.05) 0.05 (0.76) 0.10 (0.46) Diarrhea 0.05 (0.74) 0.08 (0.60) 0.04 (0.79) 0.19 (0.20) 0.06 (0.68) 0.21 (0.12) Sleep disturbance 0.20 (0.14) 0.03 (0.82) 0.16 (0.28) 0.28 (0.05) 0.03 (0.83) 0.05 (0.73) Skin itchiness/scaling 0.12 (0.38) 0.13 (0.39) 0.07 (0.61) 0.30 (0.04) 0.11 (0.47) 0.20 (0.14) Weakness 0.02 (0.89) 0.10 (0.49) 0.02 (0.91) 0.32 (0.03) (0.99) 0.02 (0.91) Chills/fever 0.18 (0.21) 0.07 (0.64) 0.19 (0.20) 0.34 (0.02) 0.07 (0.64) 0.14 (0.30) Pain related to drug 0.12 (0.41) 0.09 (0.55) 0.05 (0.73) 0.11 (0.45) 0.05 (0.73) 0.20 (0.16) treatment Hair loss 0.00 (0.99) 0.03 (0.86) 0.11 (0.44) 0.21 (0.16) 0.17 (0.26) 0.06 (0.70) Nail changes 0.10 (0.48) 0.03 (0.82) 0.12 (0.43) 0.11 (0.44) 0.07 (0.67) 0.05 (0.74) Mood changes 0.29 (0.04) 0.07 (0.66) 0.07 (0.61) 0.37 (0.01) 0.02 (0.89) 0.07 (0.63) Sore mouth 0.01 (0.97) 0.13 (0.39) 0.14 (0.35) 0.13 (0.37) 0.21 (0.16) 0.07 (0.61) Bleeding 0.15 (0.30) 0.10 (0.50) 0.36 (0.01) 0.23 (0.12) 0.22 (0.14) 0.12 (0.38) Problems with 0.13 (0.37) 0.04 (0.81) 0.24 (0.11) 0.33 (0.02) 0.02 (0.87) 0.07 (0.60) concentration Problems with sex 0.23 (0.11) 0.09 (0.55) 0.28 (0.05) 0.18 (0.22) 0.15 (0.33) 0.07 (0.63) the MAC scale. Results indicated that state anxiety was significantly associated with expectations of mood changes (moderate effect) and nervousness (large effect), both traits commonly associated with anxiety. Nonsignificant, small-to-moderate associations were also evident with expectations of sleep disturbance and problems with sex, which, again, are not uncommon traits associated with having anxiety. 21 The coping style of Anxious Preoccupation was associated, to some degree, with expectations of all 20 side effects assessed, the lowest being a small, negative association with nail changes and the highest being a moderate correlation with chills/fever. Eight of these correlations were significant, with a further seven relationships being above a small-to-moderate r value of Alternatively, there were no outstanding associations between the coping style Fighting Spirit and expectations, with the highest association being r ¼ 0.17 (nonsignificant) between this style and nausea, and also nervousness. Helpless/Hopeless (a negative, depressive coping style) showed small-to-moderate associations with three expectations (problems with sex, problems with concentration, and nervousness) and was significantly, moderately associated with the expectation of bleeding. Having a Fatalistic coping style showed no significant associations, but three correlations were r > 0.20 (a small-to-moderate association). Specifically, the more fatalistic the patients, the more they thought they would experience bleeding but the less the patients thought they would experience tiredness and a sore mouth. Similarly, the coping style of Avoidance showed no significant relationships but did show small-to-moderate negative associations with expectations of pain, skin itchiness/scaling, and diarrhea. Discussion The present study aimed to further examine the associations between patients expectations of chemotherapy-related side effects and their experiences, in individuals naive to such treatment, using the same successful methods previously used. 4 This research further aimed to contribute to the study of patient expectations by investigating the impact of psychological factors, such as anxiety and common cancer coping styles, to aid in suggesting the best interventions for future implementation.

9 1044 Whitford and Olver Vol. 43 No. 6 June 2012 Taken together, although the strength of the associations between certain expectations and experiences differed between the present study and our previous research, 4 in general, the same patterns were seen. Specifically, in most cases, the more subjective, ambiguous side effects (such as sleep disturbance, tiredness, itchiness, mood impact) showed more prominent relationships than the objective ones (such as vomiting, fever, and constipation). Other models of note, where expectation contributions were verging on significance and beta values were moderate (suggesting moderate influence in the models), were for the side effects of problems with sex, problems with concentration, and changes in taste/ appetite. Furthermore, when overall model significance is put aside in an attempt to overcome possible Type II error because of compromised power (low sample size), a total of 14 of the 20 side effects showed contributions to models above b ¼ 0.20, suggesting small-tomoderate prediction. It seems common sense that the experience of ambiguous, subjective, or vague sensations could be influenced by our expectations. However, in a few cases, objective side effects were significant predictors in the current research. In our previous study, we found that two objective expectations predicted experience, specifically, hair loss and diarrhea. In the present study, hair loss was equally found to be a strong influence. As previously argued, 4 hair loss as a result of chemotherapy is perhaps the most highly known and feared consequence of treatment for cancer. Therefore, it is not unlikely that patients would 1) have strong expectations that hair loss will occur and 2) in terms of experience, most chemotherapy regimens covered in the current research would have caused such an effect. However, elements of subjectivity cannot be ruled out, even for seemingly objective effects. As Barsky et al. 22 have outlined, negative beliefs about medical treatment can prompt patients to attribute vague, ambiguous, or pre-existing sensations in an unfavorable light following treatment initiation. Cassileth et al. 5 have suggested that this is a self-fulfilling prophecy. In the case of such phenomenological assessments of hair loss in these kinds of studies, patients may notice differences in hair consistency or some loss of hair during daily combing that may not have been obvious pretreatment. Thus, a combination of such factors may explain why some objective toxicities are influenced by expectations. Similarly, in the present study, for the seemingly objective side effect of bleeding, patient expectations significantly predicted the experience of this toxicity. Again, from a phenomenological assessment viewpoint, various patient interpretations of what bleeding constitutes need to be considered. For instance, bleeding can occur as a consequence of chemotherapy treatment because of the insertion of needles or because of nosebleeds, among others, commonly the result of low blood platelets caused by the chemotherapy. Alternatively, the idea of bleeding may be at the forefront of patients minds pretreatment because of recent surgery and current wound healing. Thus, patients may be misinterpreting the questionnaire that asks What side effects do you believe you will experience as a consequence of chemotherapy? There is a history of evidence of our subconscious ability to influence whether we bleed or not. It has long been recognized as a test in hypnotherapy practice that, when a hypnotized individual is encouraged to stop, start, or regulate bleeding after the insertion of needles in the body, many have the ability to do so very accurately. For example, regulating blood flow through a hypnotic procedure is commonly applied following dentistry procedures, such as tooth extraction, in aiding those with periodontal disease 23 to prevent blood loss during and after maxillofacial surgery, 24 and in reducing the need for transfusions in hemophilia. 25 Thus, it is probable that some of the variance found between the association of expectations and experience of bleeding during chemotherapy is influenced by the will or mindset of the patient. As an example, the expectation of bleeding was most prominent for those with high levels of negative coping styles (Helpless/Hopeless, Fatalistic, and Anxious Preoccupation). Interestingly, the possible confounding variables added to all regression analyses showed different patterns of influence. Specifically, patients ECOG performance status scores only significantly contributed to the model for tiredness, whereas nurse expectations significantly contributed to four models, including (from lowest to highest contributions) nausea,

10 Vol. 43 No. 6 June 2012 Expectations Predict Experience 1045 hair loss, diarrhea, and pain related to treatment. These findings suggest that the influence of the primary treating nurses was evident and a valuable addition to this research. All of these contributions were moderate, so perhaps with increased power, more small-to-moderate associations also would have been evident. We suggest future research in this area should collect such data to control. Psychological Influences on Expectations Close to half of the current sample evidenced clinical levels of anxiety at the time their expectations of chemotherapy-related side effects were assessed. Therefore, almost 50% of this sample would have been screened as needing psychological intervention at this stage of their treatment. The average level of state anxiety in the present study was higher (worse) than the average level from a general population study of 180 men and women in Sweden, 19 similar norms to those reported in the STAI manual for adult working men and women separately. 10 Few associations were found between patient expectations and patient levels of anxiety. As state anxiety is highly associated with one s trait or dispositional anxiety, it is possible that the associations we did find (i.e., with nervousness, mood changes, problems with sex, and sleep disturbance) were already common complaints for those with high levels of anxiety and not situation specific. However, when the five cancer coping styles assessed by the MAC scale were correlated with patient expectations of side effects, although findings were mixed, with different toxicities being associated with various adjustment styles, two specific patterns of relationships were of great interest. First, the coping style of Fighting Spirit showed no significant associations with patient expectations of toxicities, the largest value being r ¼ 0.17 (a small correlation), with 13 of the 20 associations being equal or less than r ¼ 0.10, a value considered less than small. 14 These overall results may suggest that patients with good levels of Fighting Spirit did not expect to experience the many common side effects of chemotherapy, thus perhaps providing protection or a degree of resilience. Fighting Spirit comprises items that show generally positive aspects of coping such as viewing the cancer as a challenge, fighting the cancer, making future plans, believing one will get better, believing that positivity will benefit one s health, and keeping a sense of humor. There are also some positive growth (existential) aspects, including seeing the preciousness of life and counting one s blessings. The last groups of items highlight an individual s ability to not dwell on their illness, for example, going about life as if nothing has changed, suggesting other people are more worried than oneself, and keeping busy so as not to think about the illness. 12 Depending on the prognosis of the individual in question, that is, if a patient is indeed terminal, then, interestingly, many of these items may be construed as avoidance or denial. Second, the coping style of Anxious Preoccupation showed a very different pattern. This style was associated, to some degree, with expectations of all 20 side effects, the highest being a moderate correlation with chills/fever, the lowest being a small, negative association with nail changes. Eight of these correlations were significant, with a further seven relationships above a small-to-moderate r value of 0.20, and no correlation below r ¼ On careful examination of the individual items comprising this subscale, both negative and positive aspects of coping appear to be assessed. The problematic or negative aspects of this style include a fear of cancer recurrence (or worsening of the disease), suffering great anxiety and/or anger about one s illness, feelings that the cancer prevents future planning, and even difficulty accepting that the cancer has occurred. Alternatively, what may be construed as positive aspects include engaging in behaviors that one believes will improve one s health (e.g., improving diet, exercising), trying to find as much information as possible about cancer, and wanting to be in contact with others with the same disease (perhaps such as seeking support groups). 12 These findings suggest that those with high Fighting Spirit who were positive about their cancer, those that did not dwell on their illness (as opposed to being preoccupied), did not see themselves as experiencing negative toxicities during their chemotherapy treatment. Conversely, when patients evidenced high levels of Anxious Preoccupation, there was cognitive and emotional turmoil, and behavior such as seeking information and support.

11 1046 Whitford and Olver Vol. 43 No. 6 June 2012 Although some of these aspects may seem helpful (that is, active coping strategies), the present study did not investigate which of the smaller items of the Anxious Preoccupation subscale may have been associated with expectations. However, according to research in related areas, it may be likely that any kind of preoccupation centered on oneself, whether negative or positive, may become harmful. Different terms based on alternative theories have been studied, with similar negative outcomes. For instance, in her examination of the construct of self-compassion, Neff 26 discusses the negative impact of overidentification or singular preoccupation with one s circumstances. Self-compassion is regarded as an emotionally positive self-attitude 26(p. 85) comprising three components including self-kindness, common humanity, and mindfulness. As part of the current Third Wave of psychological therapies that concentrate heavily on existentialism, mindfulness is a significant concept often taught through various meditation exercises and other Eastern methods of observing. 27 It refers to purposefully paying attention to both internal and external experiences and sensations in the present, in a nonjudgmental way (p. 85) Neff describes mindfulness as being able to hold painful thoughts and feelings in balanced awareness rather than overidentifying with them. Such overidentification is discussed as a kind of self-pity where a person becomes absorbed or immersed in their issues, perceiving them to be unique from others experiences, hence increasing a sense of isolation. Therefore, in relation to the items that comprise the measure of Anxious Preoccupation, it is obvious that fear, anxiety, and anger are detrimental to one s well-being. A lack of acceptance, inability to plan one s future, and even seeking too much information about one s diagnosis also may be harmful. The only two behaviors that may be helpful are improving one s lifestyle and seeking to meet others with cancer diagnoses, but these kinds of activities must be balanced to encourage mindfulness rather than overidentification or self-pity. Similarly, in the area of mindfulness, Baer et al. s 29 investigation of the construct validity of the Five Facet Mindfulness Questionnaire discovered that although being mindful has generally been found to be a positive state of awareness, one of the five facets of observing ( noticing or attending to internal and external experiences, such as sensations, cognitions, 29(p. 330) emotions, sights, sounds, and smells ) was associated with poor psychological wellbeing in individuals not trained in meditation. It is thought that the unbiased observing style practiced in meditation allows trained individuals to attend to both external and internal stimuli, allowing them to pass through awareness without judgment, rather than focusing attention on threatening or negative experiences (which nonmeditating individuals may do). Baer et al. 29 suggested their finding was supportive of the concept of self-focused attention and its relationship with negative emotions and various psychological disorders. Specifically, this concept has been described as a cognitive process by which attention is heavily selfdirected to form an enhanced, often absorbed awareness of oneself. This type of focus has been identified as a common component in various clinical disorders and dysfunctional states including depression, anxiety, schizophrenia, psychopathy, and alcohol abuse. 30 Mor and Winquist 31 found, through meta-analysis, that although self-focused attention was often associated with depression, anxiety, and/or negative mood, different factors moderated relationships. For instance, ruminative self-focus showed stronger associations with negative states than nonruminative self-focus (where the focus is less on emotion and more on global aspects such as one s appearance, etc.). Ruminative thinking is commonly associated with clinical depression. Once again, Mathew et al. 32 have shown that the meta-cognitive processes of mindfulness are at odds with this type of focus on oneself (rumination) in those with recurrent depression. These authors have suggested that this emotional type of preoccupation is a cognitive vulnerability to psychological distress. Thus, in addition to possible depression and other dysfunctional states, such styles of adjustment may indeed lead to situational issues, as seen in this study, where side effect experience is increased during the treatment of cancer. Limitations As outlined above, one major limitation of the present study was the compromised power (low sample size) to find some significant relationships where small or moderate effects were seen. Thus, a degree of Type II error was

12 Vol. 43 No. 6 June 2012 Expectations Predict Experience 1047 probable, highlighting that future studies with larger samples are needed to more reliably replicate the current findings. The internal reliability of some of the MAC subscales assessing cancer coping styles were low, highlighting that some of the assessments were not reliable representations of the constructs of interest. Specifically, Anxious Preoccupation and Fatalistic subscales showed Cronbach s alphas below Therefore, results including these measures need to be viewed with a degree of caution. As discussed above, perhaps on further exploration of the individual items of the Anxious Preoccupation subscale, some of the conflicting items (positive vs. negative behaviors) require separation. Attrition analyses also showed a degree of bias in the current sample suggesting that those who went on to provide follow-up data were more positive in some of their expectations of side effects occurring (i.e., hair loss and mood changes). Greater well-being, better adjustment, or higher positivity in those who continue on with health studies is not an uncommon finding, but it does continue to pose a problem for psychosocial health research outcomes. How to improve follow-up in such patient groups is very problematic, so, at the very least, attrition analyses should always be reported. Although this study only permitted new patients naive to chemotherapy treatment to participate, a high range of time since initial cancer diagnosis was found. This is likely because chemotherapy is only available in the initial phase of treatment for a few tumors, so some of the sample was probably being treated for relapse. Thus, many of the patients may have known quite a lot (theoretically) about chemotherapy or other treatments (or may have already had other treatments such as surgery and radiotherapy), although they were specifically naive to the experience of chemotherapy for the purpose of this study. Of central importance, the present study aimed to replicate previous findings by the same authors 4 but, although general results were similar (more subjective side effects showed higher associations between expectations and experience), the specific results were sometimes different (some side effects showed different magnitudes of associations between studies). Apart from limitations already mentioned, a few other methodological or sample differences could have contributed to these variations. Specifically, ECOG performance scores in the previous study were dichotomized into active vs. limited activity, whereas in the present study, we used the raw, continuous scores in regression analyses, as the skewness of such distributions was acceptable. As a result of skewness, 13 of the side effects in the previous study were transformed to help meet assumptions of normality for regression analyses, whereas data were less skewed in the present study and transformations did not improve distributions. These differences could have impacted the outcomes. When compared with 40% of the previous sample being breast cancer patients, the present study showed a greater mix of diagnoses, with around only 20% having breast cancer diagnoses; and more patients also reported having some degree of symptoms, suggesting that the current group were slightly more ill. This is further supported by the fact that only 50% expected a cure compared with 68% of the last study, thus showing either greater illness or less optimism in the current sample. Finally, more patients in the present study suggested they did not get enough information about their treatment (almost 17% compared with 6% last study). 4 Future Research Recommendations The limitations outlined above point to a need for future studies to use larger samples, more reliable assessments, and to research more homogeneous patient groups to better replicate findings and provide more reliable outcomes. As discussed in relation to the side effect of bleeding, by using phenomenological assessments of experience, it is impossible to tell whether objective or measurable effects are indeed occurring as a consequence of the treatment. According to Sohl et al., 3 even rephrasing questions (i.e., those used to assess expectations and experience) may benefit from including a reference to the specific time that the side effect will occur. This may improve (strengthen) the relationships between expectations and experience in future studies. Of particular interest, based on the novel contributions of this research, further detailed investigation into breaking down which