Secondary Logo

Journal Logo

ARTICLES

Methodology Aspects of Nausea Measuring During Pelvic Radiotherapy

Daily Nausea Measuring Is Successful to Identify Patients Experiencing Nausea

Enblom, Anna E. PhD, MSP; Steineck, Gunnar MD, PhD; Börjeson, Sussanne PhD, RN

Author Information
doi: 10.1097/NCC.0000000000000684
  • Free

Abstract

In patients with risk of nausea during radiotherapy, we do not know if results from a 5-week recall measurement of nausea at the end of the therapy period are in concordance with accumulated results from daily nausea measurement during the therapy period; nor do we know if use of a method to measure nausea affects the magnitude of the potential difference in quality of life (QoL) between nauseated patients and patients free from nausea. During both chemotherapy1 and radiotherapy,2 patients are at risk of experiencing nausea as an adverse effect. However, to the best of our knowledge, methodology studies regarding nausea measuring during specifically radiotherapy have not previously been published.

Nausea Measuring

There are a number of valid instruments for chemotherapy-induced emesis that will say nausea and vomiting, while far fewer instruments have been developed that are satisfactory or applicable for measuring radiotherapy-induced nausea.3,4 If the patient experiences nausea but does not vomit, cancer nursing professionals tend to not register that the patient experiences emesis and thus underestimates the nausea symptom experience. In 41,933 individuals with a variety of cancer diagnoses receiving a variety of cancer therapies, professionals accordingly identified only half of the patients who actually were nauseated.5 Cancer care professionals tend to consider it more important to control vomiting than nausea, while the patients find that it is just as important to control nausea as it is to control vomiting.6 Thus, patient-reported measures, distinguishing nausea from vomiting, seem to be preferable.5,6 Most instruments, however, measure summarized emesis experience. They do not distinguish nausea from vomiting,3,4 although nausea and vomiting are 2 different kinds of symptoms.

Most nausea-measuring methods are developed for chemotherapy-induced nausea. They often cover daily nausea measuring during, for example, 5 to 10 days (the day for chemotherapy and the 4 to 9 following days).3,4 Measuring nausea daily during radiotherapy may induce considerably larger patient burden; fractioned radiotherapy is often given for several weeks.2,7 Potentially, cancer nursing professionals thus tend to avoid repeatedly conducted nausea measuring6 and instead prefer measurement using longer recall periods. However, it is not known if results from a longer recall period, covering the entire radiotherapy period, would be found to be comparable with results from accumulated daily nausea measurements, repeated during the radiotherapy period.

Pathology and Prevalence of Radiotherapy-Induced Nausea

Radiotherapy to abdominal or pelvic fields induces cellular damages in the gastrointestinal tract, which leads to release of serotonin. The serotonin activates serotonin receptors on closely associated vagal afferents fibers resulting in transmitter release at the level of the dorsal vagal complex, also known as the vomiting center. The activity in the vomiting center, located in the medulla of the brain stem close to the area postrema, causes the sensation of nausea. If the activity is strong enough, vomiting occurs.8

Nausea was experienced by 28%9 to 39%10 of patients during radiotherapy, irradiated over a large variety of fields, and is common during both the curative and palliative phases.11 Fifty percent,12 60%10,13 or 70%14,15 of patients receiving pelvic-abdominal radiotherapy experienced nausea. A small study (n = 58) indicated even higher occurrence of nausea in patients irradiated specifically to abdominal fields; more than 80% experienced at least 1 episode of nausea within the radiotherapy period, according to accumulated daily measurements.16 Research regarding radiotherapy-induced nausea, especially longitudinal research, is, however, highly underrepresented compared with research on chemotherapy-induced emesis; more observational studies would be welcomed.17 There are several indications that radiotherapy-induced nausea, in particular, is still underestimated5 and undertreated2 and even undermeasured.6 A potential reason for this may be that cancer nursing professionals find it difficult to identify patients experiencing nausea during radiotherapy. In a study of professionals (n = 561) and patients (n = 368) during radiotherapy and chemotherapy, a third of the professionals and half of the patients stated that there was no patient assessment of emesis during the treatment period. The main reason for not measuring emesis was that two-thirds of the professionals and half of the patients believed that emesis simply has to be tolerated.6 In a previous study, we found that one-third of patients with radiotherapy-induced nausea asked for more treatment for nausea.10

Nausea in Relation to QoL

A potential reason for undertreating radiotherapy-induced nausea may be that the negative impact of nausea has not been sufficiently investigated. Nausea reduces QoL during chemotherapy18 and also during radiotherapy according to a few previous studies.10,16,19 Quality of life often varies depending on health or disease status; some researchers thus define aspects of QoL that are related to health and disease status as “health related QoL.”20 However, only 11 of 152 studies of pelvic radiotherapy measured QoL, according to a review.21 Many clinicians and researchers suggest it is no meaning to measure QoL in patients with risk of nausea during radiotherapy, simply because of the fact that patients often perceive mild intensity of radiotherapy-induced nausea. Accordingly, the relation between radiotherapy-induced nausea and QoL seems to be sparely investigated.10,16,19

Nausea Experience Measuring According to the Theory of Unpleasant Symptoms

In this study, we study the application of the middle-range theory of unpleasant symptoms22 in a routine radiotherapy care setting. The middle-range theory enables cancer nursing professionals to combine clinical practice and theory and to study the science of nursing and its respective theories for improved quality of care. This theory, introduced in 1995, presents 3 factors influencing symptom experience: physiological factors, psychological factors, and situational factors, which cause individuals to experience the same symptoms in different ways. Symptom experience has 3 main components: the symptoms the individual is experiencing (eg, occurrence and intensity of nausea), the factors that influence symptoms (eg, the situation and timing of nausea measurement), and the consequences of this experience (eg, worsened QoL). Although symptoms differ from each other, they accordingly share some dimensions, such as intensity, timing, and degree of perceived symptom burden. The theory of unpleasant symptoms thus provides understanding of patients' symptom experience, for example, nausea experience. The theory guides nursing practice for symptom assessment and management for various populations with different symptom experiences, for example, patients experiencing distressing nausea. For example, the theory suggests that perceived occurrence and intensity of a symptom may vary depending on the situation and timing of the symptom measuring.22 It would be interesting to study if the timing of measurement, in terms of different recall periods, affects reported nausea in a routine radiotherapy setting. For the measurement of nausea,3,4 several types of scales exist for grading intensity of nausea, for example, category scale (4–5 categories) and visual analog scale (VAS),23,24 which are both well-established scales used during cancer care in general.3,4,23,24 Further, the nausea item with the established multi-item QoL instrument Functional Assessment of Cancer Therapy–General (FACT-G) may be used for nausea measuring, graded on a 5-grade numeric rating scale.25 It is not known if one of the scales is more suitable than the other during fractioned radiotherapy, with regard to patient compliance. Also, knowledge is needed regarding how the timing for measuring nausea affects the reported nausea. The symptom assessment aims, according to the theory of unpleasant symptoms,22 to identify and manage symptoms in order to prevent negative consequences of the symptom in daily life.

Objective

The objective of this study was to investigate if a 5-week recall measure of nausea covering the entire radiotherapy period was comparable with accumulated daily nausea measures. We also investigated if category scales produced results regarding patient compliance and nausea intensity comparable with results from using nausea VAS and the nausea numeric rating nausea scale within the FACT-G. Furthermore, we wanted to determine if use of either method to measure nausea, 5-week recall or daily measurement, affected the magnitude of the potential difference in QoL between nauseated patients and patients free from nausea.

Methods

This longitudinal study was approved by the regional ethics committee (02-420, M167-04). It included 200 patients undergoing radiotherapy. These patients also participated in a study regarding the effect of antiemetic acupuncture compared with sham acupuncture, reported previously.15 The study criteria and size of the studied cohort were designed primarily for that study. The study included patients at 2 Swedish university hospitals.

Inclusion and Exclusion Criteria

Inclusion Criteria. Patients (Figure 1) who were at least 18 years of age and had gynecologic, anal, rectal, colon, stomach, pancreatic, or testicular cancer tumors were included if they were planned for irradiation over an abdominal or pelvic field of at least 800-cm3 volume and 25-Gy dose and if they had the physical, mental, and linguistic capacity to give informed consent. Only patients delivering at least 1 week of nausea measures were included in this analysis.

Figure 1
Figure 1:
The numbers of patients screened, included, and participating in the QoL measurement and the daily and the 5-week recall nausea measurements. The numbers of patients decreased with time over the radiotherapy weeks because of the individual length of the radiotherapy period (median, 5 weeks). Abbreviations: FACT-G, Functional Assessment of Cancer Therapy–General; QoL, quality of life.

Exclusion Criteria. Those with antiemetic treatment or persistent emesis within 24 hours before start of radiotherapy or acupuncture treatment during the past year for any indication, or ever for emesis, were excluded.

Of the 522 screened patients, 169 did not meet the study criteria, 138 did not want to participate (not interested, n = 54; had no time, n = 37; felt too tired/ill, n = 37; gave no reason, n = 10), whereas 215 were originally included. Of these 215, 15 did not participate in the study (patient died, n = 2; radiotherapy was cancelled, n = 2; patient dropped out from the study within the first week, n = 9; patient did not deliver any data at all; reason unknown, n = 2). Therefore, 200 patients participated in this study. Of the 200 patients, 157 patients (79%) delivered data at the end of the radiotherapy period (Figure 1).

Setting and Treatment

The patients received radiotherapy for a median time of 5 weeks, 1 fraction a day (Monday through Friday), with or without concomitant chemotherapy. Oncologists prescribed rescue pharmacological treatment for emesis7 according to ordinary clinical routines specified for various dose levels in the Swedish Medicine Information Engine (http://www.fass.se). All patients received penetrating or nonpenetrating acupuncture 2 to 3 times per week for emesis, according to previously described standardized routines.15

Data Collection

The patients provided the patient-reported data to the study evaluator, who was independent from the radiotherapy, by postal mail (prepaid envelopes) or by use of answering boxes at the radiotherapy department of the oncology clinics. The patients delivered no questionnaires directly to the radiotherapy professionals or to the study coordinator.

DESCRIPTIVE VARIABLES

The patients answered written sociodemographic descriptive questions the day before start of radiotherapy, and a study coordinator collected data regarding details of the radiotherapy from medical records. The descriptive variables are shown in Table 1.

Table 1
Table 1:
Descriptive Variables of the Patients

NAUSEA ASSESSMENT

Preceding the study, we satisfactorily secured face-to-face validity regarding the clarity of the 3 different nausea scales used in this study, through individual patient interviews with patients undergoing radiotherapy (n = 9). To measure nausea, we used the 5-grade nausea category scale and the 100-mm nausea VAS described in Table 2, originally developed by Börjeson et al26 for patients during chemotherapy. The nausea category scale covers phrases representing each category, without using numbers representing the categories. The original nausea category scale26 covered the categories “No nausea,” mild nausea,” “moderate nausea,” and “severe nausea.” We added the fifth category, “very severe nausea,” to increase sensitivity to detect changes. We secured the accuracy for the target population of patients undergoing radiotherapy according to the previously used10 methodology described by Steineck and coworkers,27 which complies with the clinimetric methodology. Clinimetrics covers feasibility (in terms of patient compliance, sensitivity, and specificity), validity, and reliability of single-item scales and other expressions that are used to describe or measure symptoms, physical signs, and other distinctly clinical phenomena.28 The nausea category scale has been previously applied in patients undergoing radiotherapy.10,29 Preceding the current study, we observed that the nausea category scale, divided into 2 parts (“no nausea” vs “mild nausea” to “very severe nausea”), completely correlated (r = 1.0) to a nominal category question (“yes” or “no”) regarding occurrence of nausea, indicating satisfactorily content validity. This pilot methodology testing covered 456 nausea registrations made by 10 patients during pelvic-abdominal radiotherapy. Further, we tested test-retest reliability of the nausea VAS and the nausea category scale in 36 patients, answering the nausea questions 2 times (r = 0.98 for VAS and r = 1.0 for category scale).29 Nausea was defined in the questionnaire: “An unpleasant nauseating sensation in the gastrointestinal tract that may or may not lead to vomiting when the sensation increases.”24 The patients completed the daily nausea measurements in writing, on their own without assistance, every morning (Mondays through Sundays) during the entire radiotherapy treatment, 14 days afterward, and at a follow-up 4 weeks after the end of radiotherapy and sent their report to the evaluator every seventh day. The day after the last radiotherapy fraction, the patients performed a 5-week recall nausea measurement covering nausea within the entire radiotherapy period (Table 2). Besides measuring nausea using the nausea category scale and the nausea VAS, we measured nausea occurring within the past week using the nausea numeric rating scale within FACT-G25 (Table 2), at the start and at the day after the last radiotherapy fraction. The different kinds of nausea measurements within the study were conducted independently from the routine radiotherapy care.

Table 2
Table 2:
Measures of Nausea Daily and Using a 5-Week Recall

QOL ASSESSMENT

During the day before the start of radiotherapy and during the day after the end of radiotherapy, the patients graded their QoL using the Swedish version30 of the extensively used31 FACT-G, version 4.25 The higher the FACT-G score, the better the QoL. It is divided into 4 subscales: physical well-being (7 items, eg, “I have nausea”), functional well-being (7 items, eg, “I am content with the quality of my life right now”), social/family well-being (7 items, eg, “I get emotional support from my family”), and emotional well-being (6 items, eg, “I worry that my condition will get worse”). Every item is answered on a 5-grade numeric rating scale, ranging from “0 = not at all” to “4 = very much.” Functional Assessment of Cancer Therapy–General is reliable and valid.32,33

Statistical Analyses

We calculated correlations between the daily nausea category scales and the nausea VAS measurements, using Spearman correlation coefficient, Sr. For each step on the nausea category scale, we calculated the patients' variation (interquartile range) in nausea VAS intensity grading. We selected the nausea category scale registrations that covered the same recall period that the nausea numeric rating scale from FACT-G covered (n = 200 registrations at the start and n = 157 registrations at the end of the radiotherapy period, summed n = 357 registrations) and calculated Sr between these 2 types of nausea intensity scales.

We categorized patients into the groups, “experienced nausea” (patients experiencing nausea at least 1 episode) and “not experiencing nausea” (patients who were free from nausea during the entire radiotherapy period), based on (a) on the daily category scales and (b) the 5-week recall. A χ2 test compared the proportion of patients reporting nausea occurrence according to the daily nausea measurements, and the proportion of patients reporting nausea according to the 5-week recall nausea measurement, presented as relative risk (RR) for nausea with 95% confidence intervals (CIs). Mann-Whitney U test compared patients experiencing and not experiencing nausea, regarding QoL in terms of the FACT-G subscores. These analyses were made separately for the daily and the 5-week recall nausea measurement. The Statistical Package for the Social Sciences for Windows version 23.0 (IBM Corp, United States) was used, the analyses included no imputation of data, and the significance level was 5%.

Results

Patient Characteristics

Most patients were retired women, receiving radiotherapy over the pelvis for a gynecological tumor. Forty percent consumed any type of antiemetic agent during the radiotherapy period, and a little more than a quarter received concomitant chemotherapy (Table 1). Figure 1 presents the number of patients delivering data during the radiotherapy period for the median time 5 weeks and at the start and end of therapy.

Patient Compliance Using Different Scales for Measuring Nausea Intensity

Of the total sum of 10219 days of daily nausea registrations offered to the 200 patients, both the nausea category scale and the nausea VAS were answered on 8601 days (84%). Nausea VAS was not answered on 1610 days (15%), whereas the nausea category scale was not answered on 8 days (0%). Of the 357 nausea registrations offered using both the nausea numeric rating scale within FACT-G regarding nausea within the past week and the accumulated daily nausea category scale, both scales were answered during 313 registrations. One single patient missed answering both scales once, while the nausea numeric rating scale within FACT-G was not answered during 32 registrations (9%), and the nausea category scale was not answered during 11 of the registrations (3%).

Concordance Between Different Scales for Measuring Nausea Intensity

For each category of the 8601 nausea category scale registrations, the nausea VAS (median, interquartile range) in millimeters were as follows: no nausea: 0, 0 to 0; a little nausea: 17, 11 to 24; moderate nausea: 38, 29 to 48; much nausea: 68, 58 to 77; and very much nausea: 86, 78 to 94. The correlation between the nausea category scale and the nausea VAS was 0.622 (significant at .01 level). The correlation was 0.315 (significant at .001 level) between the accumulated daily nausea category scale and the nausea numeric rating scale within FACT-G, regarding nausea within the past week. In 265 ratings of nausea on the nausea category scale, the patients registered “no nausea.” However, in 31 of these nausea measurements (12%), the patients answered that they were nauseated when using the nausea numeric rating scale within the FACT-G (range, 1 [a little bit] to 4 [very much]). Also, of the total of 262 registrations of “0 = not at all” on the nausea numeric rating scale within FACT-G nausea item, 28 patients (11%) reported that they actually were nauseated in their answers in the accumulated daily nausea category scale registrations (range, mild to very severe nausea) (Figure 2).

Figure 2
Figure 2:
Concordance between a nausea category scale (ranged from “no” to “very severe” nausea) and a nausea numeric rating scale within Functional Assessment of Cancer Therapy–General (ranged “not at all” to “very much” nausea) to measure intensity of nausea. Numbers of answers within the answering alternatives are presented for the 313 registrations with both types of nausea scales.

Concordance Between Results From the 5-Week Recall and the Daily Nausea Measurement

According to the 5-week recall nausea category scale measurement, 57 of the 157 patients (36%) who answered had experienced nausea during the radiotherapy period. However, according to the accumulated daily nausea category scale measurements, 94 of the 157 patients (60%) actually experienced nausea during the radiotherapy period; that will say the probability to register nausea occurrence was higher according to the daily measurement than according to the 5-week recall (RR, 1.65; CI, 1.29–2.10). Of the 94 patients who according to the accumulated daily nausea category scale measurements experienced nausea, 39 (42%) stated that they had not experienced nausea according to the 5-week recall nausea category scale measurement (Figure 3). These 39 patients experienced a median 2 days of nausea according to the accumulated daily category scale nausea measurements (interquartile range, 1–4 days; range, 1–26 days). Of the 57 patients who according to the 5-week recall nausea category scale measurement experienced nausea within the radiotherapy period, 2 patients did not register any nausea episodes at all according to the accumulated daily category scale nausea measures (Figure 3).

Figure 3
Figure 3:
Concordance between accumulated daily nausea measurements and a 5-week recall nausea measurement regarding occurrence of nausea. Numbers of patients answering the alternatives are presented for the 157 patients who provided both types of nausea measurements.

Differences in QoL Between Patients Experiencing or Not Experiencing Nausea

According to both the 5-week recall nausea category scale measurement and the accumulated daily category scale measurements, the patients who experienced nausea during the radiotherapy period reported lower QoL at the end of the radiotherapy than did the patients who were free from nausea. This relation was seen according to the physical (P < .001 based on 5-week recall measurement/P < .001 based on accumulated daily measurements) and the functional (P = .049/P = .013) FACT-G subscales. Regarding the social (P = .241/P = .444) and the emotional (P = .071/P = .119) subscales, there were no statistically significant differences between patients with nausea and patients free from nausea, irrespective of the timing of measuring nausea (5-week recall or accumulated daily measurements) (Figure 4).

Figure 4
Figure 4:
Quality of life (n = 157): median scores on the subscores of Functional Assessment of Cancer Therapy–General (FACT-G) at the end of radiotherapy in patients who experienced nausea and in patients who were free from nausea, according to 5-week recall nausea measurement at the end of the radiotherapy period (left) and according to accumulated daily nausea measures (right). Statistically significant differences are presented. Abbreviation: NS, statistically significant difference.

Discussion

In this study, we found that the reported prevalence of nausea varied greatly, depending on the timing of the nausea measuring; almost half, 42%, of the patients who experienced nausea according to the accumulated daily nausea measurement method did not report that they had experienced nausea using the 5-week recall measurement method. According to both the 5-week recall and the accumulated daily measurement, the patients who experienced nausea during the radiotherapy period reported worse physical and functional aspects of QoL than patients who were free from nausea within the entire radiotherapy period. There was a high concordance between results from the nausea category scale and the nausea VAS regarding patient compliance and nausea intensity during radiotherapy, whereas the patient compliance and concordance were lower using the nausea numeric rating scale within the FACT-G.

We applied the theory of unpleasant symptoms22 to study how the nausea varied depending on the situation and timing for the measurement. That almost half, 42%, of the patients who experienced nausea according to daily nausea measurements did not report nausea using a 5-week recall measurement should be interpreted as indicating either that the patients had forgotten their nausea at the end of the therapy or that they had underestimated the nausea. Being in the new situation22 of having ended the radiotherapy might bring them to marginalize the nausea that they experienced during the radiotherapy period. For example, if patients experienced nausea for only a couple of days, perhaps at the end of the therapy they may have thought that their experiences were comparable with “no nausea.” When patients experience a change in their health state, they may change their internal standards (ie, recalibration), values (ie, reprioritization), or meaning (ie, reconceptualization) of the phenomenon that healthcare professionals or researchers are asking them to self-report.34 For example, patients who may experience a severity of nausea during cancer therapy greater than they had ever before experienced prior to the development of the cancer and the resulting therapy may recalibrate what nausea means to them. They may no longer think that the nausea they experienced before beginning radiotherapy should have been defined as nausea. This so-called response-shift tendency34 over time makes it difficult to compare results from daily nausea measurements, measurements that include the very first days of daily nausea measurements, with a 5-week recall at the at the end of the cancer therapy. Because the situation and timing of the nausea measurement clearly affected nausea symptom experience, this verified the applicability of the middle-range theory of unpleasant symptoms in a routine radiotherapy setting. Accordingly, it is impossible to correctly interpret results from studies that do not present details regarding the time frame for measurement. For example, Hafiz et al35 reported an approximately 50% lower proportion of nauseated patients than we did according to the daily nausea measurements; that study reported that only 39% of 99 patients irradiated over the pelvis for gynecological tumors experienced nausea (our study, 60%/their study, 39% = 1.53). However, they provided no details about the timing of measurements during the radiotherapy period.

The middle-range theory of unpleasant provides clinically relevant understanding of patients' symptom experience. The theory guides nursing practice for symptom assessment and management for various populations with different symptom experiences, for example, patients with distressing nausea during radiotherapy. The symptom assessment and management aim to prevent negative consequences of the symptom in daily life.22 The patients who experienced nausea during the radiotherapy period graded worse physical and functional QoL at the end of the radiotherapy period than did patients who were free from nausea within the entire radiotherapy period, according to both the 5-week recall nausea measurement and the daily accumulated measurements. This was in line with the theory of unpleasant symptoms, regarding the consequences of symptoms.22 It was also in line with previous findings regarding impact on QoL of chemotherapy-induced18,36 and radiotherapy-induced10,16,19 nausea. One review37 reports that QoL, measured using a variety of methods, decreased during radiotherapy. The worsening in QoL was probably related to a variety of adverse effects; nausea was one of these adverse effects among others, and the relation between nausea and QoL was not specifically investigated. In a study of 367 patients receiving radiotherapy over a large variety of radiotherapy fields, grading of both QoL using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core Questionnaire and severity of nausea and other adverse effects were worse at the end of radiotherapy compared with at the start of therapy.38 Similar worsening of adverse effects and QoL with time was seen by others (n = 41).39 In a small study of 48 patients receiving radiotherapy over abdominal fields, higher nausea severity was related to worsened physical, role, and social functioning measured using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core Questionnaire.16 In our previous study of 368 patients receiving radiotherapy over a variety of fields,10 we found that nauseated patients experienced worsened QoL measured with single-item questions40 than patients who did not experience nausea. Our current study indicates that even during modern radiotherapy nauseated patients experience worse QoL compared with patients with complete control of nausea. In our study, the patients who did not experience nausea experienced even better QoL, in terms of higher scores regarding physical, social/family, and emotional subscores, than normative FACT-G data from a reference group of 2236 adult patients with cancer in general.31 This underscores the importance of symptom managing, in line with the theory of unpleasant symptoms.22 In clinimetrics, unlike psychometrics, homogeneity of multi-items is not requested, and what matters is the single-item scale's capacity to discriminate between different subgroups of patients or to reflect changes over time.28 Our QoL results confirmed that the methods for nausea measuring that have been studied were able to discriminate between subgroups of patients.

According to the theory of unpleasant symptoms,22 unpleasant symptoms share the dimension symptom intensity, which we measured in different ways in this study. The correlation between the registered intensity on nausea VAS and the nausea category scale may be interpreted as high correlation.41 Patients not experiencing nausea graded 0 on the nausea VAS as expected. In the nauseated patients, the category scale divided the nausea VAS into 4 nearly equally large parts of approximately 24 mm per part. This was in line with findings from our previous study regarding chemotherapy-induced nausea.26 The mean values for the verbal categories in that study as compared with the median values for the verbal categories in the current study were as follows: no nausea = 0.7 mm compared with 0 mm, mild nausea = 24.8 mm compared with 17 mm, moderate nausea = 48.3 mm compared with 38 mm, and severe nausea = 75.1 mm compared with 68 mm. For very severe nausea, which was a category that did not exist in the previous study,26 the median value in our study was 86 mm. Patient compliance was high using both types of scales but was even higher for the category scale. This indicates that the daily nausea measurements did not induce too much patient burden, in line with other data collections applying the clinimetric27,28 methodology10,15,26,27,42 for patient validation and feasibility testing.27 A high correlation between results from 2 types of scales is often interpreted as indicating that the 2 scales measure the same factor. However, a high correlation does not indicate similar sensitivity.28 The nausea VAS would be preferable if the sensitivity of the scale is the most important factor, while the nausea category scale would be preferable if maximal patient compliance is the most important factor. The registrations using the nausea numeric rating scale within the FACT-G reached lower patient compliance, and the results did not satisfactorily correlate with the results from the nausea category scale. A valid scale should measure the phenomena that the scale intends to measure.27,28 When the patients were to register nausea using the nausea category scale and the nausea VAS, the patients were provided with a definition of nausea24 to secure the validity, because symptom experiences are individual, according to the theory of unpleasant symptoms.22 This definition was similar to how patients defined nausea during our previous face-to-face validity interviews. To use a definition minimizes the noise in the measurement and helps the observer to understand the meaning of the patient's answers on the scales. The nausea numeric rating scale within the FACT-G does not include any nausea definition; it is plausible that this affected the patients' answers and thus may explain the rather low concordance between the nausea category scale and the nausea numeric rating scale within the FACT-G. This indicates that, to evaluate patients' nausea, specific nausea intensity scales are warranted even if patients answer FACT-G and thus within the framework of that instrument do report nausea. Thus, cancer nursing professionals may apply the nausea category scale or the nausea VAS to measure nausea in routine radiotherapy practice (Figure 5).

Figure 5
Figure 5:
The nausea category scale (left) and the nausea visual analog scale (VAS; right). The nausea VAS is 100 mm.

Because 60% of the patients experienced nausea according to the accumulated daily nausea measuring, and the nauseated patients experienced worse QoL than did the patients not experiencing nausea, cancer nursing professionals should measure and adequately treat radiotherapy-induced nausea. According to evidence-based antiemetic recommendations,7,43 patients receiving radiotherapy to pelvic fields should receive prophylaxis or rescue with dexamethasone, a dopamine receptor antagonist, or a 5-HT3-receptor antagonist. If abdomen is irradiated, prophylaxis with a 5-HT3 receptor antagonist and optional dexamethasone should be offered. Our study was conducted within routine radiotherapy care, and only 40% of the patients received any antiemetic agent, in contrast to the 60% who experienced nausea. However, according to the 5-week recall, 36% reported that they had experienced nausea, which was a more similar proportion to the proportion of 40% consuming antiemetics. This observation indicates the clinical value of repeatedly conducted nausea measurements during the radiotherapy period. Our previous study regarding radiotherapy-induced nausea presented that one-third of the nauseated patients asked for more treatment of nausea, whereas 41% had chosen not to consume antiemetics.10 In the current study, we did not collect data regarding whether the nauseated patients were not offered any antiemetics or if they were offered but rejected antiemetics. To be able to identify patients experiencing nausea and to evaluate emesis control during antiemetic treatment procedures, nausea should be measured repeatedly.

Strengths of our study are the nursing theory-guided research objectives, the longitudinal design, and the high answering rates in the daily nausea measuring and in the baseline measuring. We studied the application of 3 main components of the middle-range theory of unpleasant symptoms22 in routine radiotherapy care: the symptoms the individual is experiencing (ie, radiotherapy-induced nausea experience), the factors that influence symptoms (ie, the situation/timing of measurement), and the consequences of this symptom experience (ie, the relation to QoL). Although patient-reported measuring may induce an extra burden on the patients, the patients often perceive the measuring per se as beneficial. Dunberger et al42 reported that of 1068 patients with cancer who participated in questionnaire studies applying clinimetric methodology 95% considered that the data collection was valuable and 54% felt that their participation per se had positively affected them. Through collecting data using several scales in our study, we provided detailed information regarding nausea and symptom distress in terms of worsening QoL during radiotherapy. A weakness of our study may be the lower participation rate in the 5-week recall nausea measuring. The lower participation rate may be a result per se; it seems easier to receive a high response rate during the time the patients have frequent contact with the radiotherapy healthcare professionals. Gradual onset of nausea will be identified only if a baseline is established, and patients are routinely screened for patient-reported clinically meaningful changes of toxicities throughout the trajectory of treatment. Our daily nausea measuring enabled such screening. However, if goals differ from those we set, then prolonged recall periods longer than 24 hours may be suitable, whereas a 5-week recall period seems too long for many intentions. In a previous study, we feasibly measured nausea using 1-week recall,10 similar to the weekly recalls applied in Patient-Reported Outcome Measures Information System.44 Weekly recalls may potentially be an alternative if daily measuring is not possible or feasible to conduct in frail patients. In this study, we used a traditional patient diary that included the daily nausea measurements, answered in writing. However, future studies may have to take into consideration the possibility of repeatedly screening of symptoms using new technology, a mobile-phone based system (an “app”), and may replace traditional methods. A pilot study of the use of mobile-phone reporting has found this approach to be promising, also in patients with cancer. The patients were comfortable with the technology and were aware that their answers were monitored in real time and were being taken into account when planning further treatment; this was suggested to reinforce the patients' feeling of involvement in their own care.45 Our observation that the nauseated patients experienced lower QoL, using well-established methods for measuring QoL,25,30–33 indicates that the nausea measurements detected clinically meaningful toxicities irrespective of the length of the recall period.

Cancer nursing professionals may apply either nausea category scales or nausea VAS to measure nausea in routine radiotherapy care, but the category scale might be easier for patients to understand, while the VAS is more sensitive to detect changes. If clinicians or researchers want to detect nausea with high validity and sensitivity, daily measuring of nausea is preferable to retrospective recalls of several weeks. Our study implicates that cancer nursing professionals should measure nausea repeatedly during the radiotherapy period in order to identify patients at risk of nausea and worsened QoL, to be able to deliver evidence-based antiemetic treatment strategies. Cancer nursing practice care would welcome studies exploring the caring needs in patients who experience distressing nausea but who reject pharmacological antiemetic treatment, to be able to deliver patient-preferred care.

ACKNOWLEDGMENTS

The authors thank the participating patients; Boel Lindberg and Ingrid Tillgren for coordinating; Anna Johnsson, Marianne Frid, Annica Tomasson, Clary Skoglund, Eva Ahlner, and Lotta Robert for acupuncture treatments; and the health care professionals at the radiotherapy departments for cooperation. The authors also thank Prof Mats Hammar for valuable methodological contributions, Erik Onelöv for statistical contributions, and Mr Lawrence Lundgren for linguistic editing.

References

1. Navari RM, Aapro M. Antiemetic prophylaxis for chemotherapy-induced nausea and vomiting. N Engl J Med. 2014;374:1356–1367.
2. Feyer P, Jahn F, Jordan K. Radiation induced nausea and vomiting. Eur J Pharmacol. 2014;722:165–171.
3. Martin CG, Rubenstein EB, Elting LS, et al. Measuring chemotherapy-induced nausea and emesis. Cancer. 2003;98:645–655.
4. Brearley SG, Clements CV, Molassiotis A. A review of patient self-report tools for chemotherapy-induced nausea and vomiting. Support Care Cancer. 2008;16:1213–1229.
5. Laugsand EA, Sprangers MA, Bjordal K, Skorpen F, Kaasa S, Klepstad P. Health care providers underestimate symptom intensities of cancer patients: a multicenter European study. Health Qual Life Outcomes. 2010;8:104.
6. Vidall C, Fernández-Ortega P, Cortinovis D, et al. Impact and management of chemotherapy/radiotherapy-induced nausea and vomiting and the perceptual gap between oncologists/oncology nurses and patients: a cross-sectional multinational survey. Support Care Cancer. 2015;23:3297–3305.
7. Ruhlmann CH, Jahn F, Jordan K, et al. 2016 updated MASCC/ESMO consensus recommendations: prevention of radiotherapy-induced nausea and vomiting. Support Care Cancer. 2017;25:309–316.
8. Abdelsayed GG. Management of radiation-induced nausea and vomiting. Exp Hematol. 2007;35(suppl 1):34–36.
9. Maranzano E, De Angelis V, Pergolizzi S, et al. Italian Group for Antiemetic Research in Radiotherapy–IGARR. A prospective observational trial on emesis in radiotherapy: analysis of 1020 patients recruited in 45 Italian radiation oncology centres. Radiother Oncol. 2010;94:36–41.
10. Enblom A, Bergius Axelsson B, Steineck G, et al. One third of patients with radiotherapy-induced nausea consider their antiemetic treatment insufficient. Support Care Cancer. 2009;17:23–32.
11. Chiu N, Chiu L, Popovic M, et al. Latest advances in the management of radiation-induced pain flare, nausea and vomiting. Ann Palliat Med. 2016;5:50–57.
12. Ruhlmann CH, Christensen TB, Dohn LH, et al. Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): a multinational, randomised, placebo-controlled, double-blind, phase 3 trial. Lancet Oncol. 2016;17:509–518.
13. Mystakidou K, Katsouda E, Linou A, et al. Prophylactic tropisetron versus rescue tropisetron in fractionated radiotherapy to moderate or high emetogenic areas: a prospective randomized open label study in cancer patients. Med Oncol. 2006;23:251–262.
14. IGARR (the Italian Group for Antiemetic Research in Radiotherapy). Int J Radiat Oncol Biol Phys. 1999;44:619–625.
15. Enblom A, Johnsson A, Hammar M, et al. Acupuncture compared with placebo acupuncture in radiotherapy-induced nausea—a randomized controlled study. Ann Oncol. 2012;23:1353–1361.
16. Poon M, Dennis K, DeAngelis C, et al. A prospective study of gastrointestinal radiation therapy-induced nausea and vomiting. Support Care Cancer. 2014;22:1493–1507.
17. Dennis K, Poon M, Chow E. Nausea and vomiting induced by gastrointestinal radiation therapy: current status and future directions. Curr Opin Support Palliat Care. 2015;9:182–188.
18. Sommariva S, Pongiglione B, Tarricone R. Impact of chemotherapy-induced nausea and vomiting on health-related quality of life and resource utilization: a systematic review. Crit Rev Oncol Hematol. 2016;99:13–36.
19. Yee C, Drost L, Zhang L, et al. Impact of radiation-induced nausea and vomiting on quality of life [published online ahead of print May 28, 2018]. Support Care Cancer 2018.
20. Bakas T, McLennon SM, Carpenter JS, et al. Systematic review of health-related quality of life models. Health Qual Life Outcomes. 2012;10:134.
21. Sodergren SC, Vassiliou V, Dennis K, et al. EORTC Quality of Life Group. Systematic review of the quality of life issues associated with anal cancer and its treatment with radiochemotherapy. Support Care Cancer. 2015;23:3613–3623.
22. Lee SE, Vincent C, Finnegan L. An analysis and evaluation of the theory of unpleasant symptoms. ANS Adv Nurs Sci. 2017;40:E16–E39.
23. Rhodes VA, McDaniel RW. Nausea, vomiting, and retching: complex problems in palliative care. CA Cancer J Clin. 2001;51:232–248; quiz 249–252.
24. Rhodes VA, Watson PM, Johnson MH. Development of reliable and valid measures of nausea and vomiting. Cancer Nurs. 1984;7:33–41.
25. Cella D, Tulsky D, Gray G, et al. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol. 1993;11:570–579.
26. Börjeson S, Hursti TJ, Peterson C, et al. Similarities and differences in assessing nausea on a verbal category scale and a visual analogue scale. Cancer Nurs. 1997;20:260–266.
27. Steineck G, Bergmark K, Henningsohn L, al-Abany M, Dickman PW, Helgason A. Symptom documentation in cancer survivors as a basis for therapy modifications. Acta Oncol. 2002;41:244–252.
28. Fava GA, Tomba E, Sonino N. Clinimetrics: the science of clinical measurements. Int J Clin Pract. 2012;66:11–15.
29. Enblom A, Tomasson A, Hammar M, et al. Pilot testing of methods for evaluation of acupuncture for emesis during radiotherapy: a randomised single subject experimental design. Acupunct Med. 2011;29:94–102.
30. Bonomi AE, Cella DF, Hahn EA, et al. Multilingual translation of the Functional Assessment of Cancer Therapy (FACT) quality of life measurement system. Qual Life Res. 1996;5:309–320.
31. Brucker PS, Yost K, Cashy J, Webster K, Cella D. General population and cancer patient norms for the Functional Assessment of Cancer Therapy–General (FACT-G). Eval Health Prof. 2005;28:192–211.
32. Ashing-Giwa K, Rosales M. A cross-cultural validation of patient-reported outcomes measures: a study of breast cancers survivors. Qual Life Res. 2013;22:295–308.
33. Holzner B, Kemmler G, Sperner-Unterweger B, et al. Quality of life measurement in oncology—a matter of the assessment instrument? E J Cancer. 2001;37:2349–2356.
34. Schwartz CE. Applications of response shift theory and methods to participation measurement: a brief history of a young field. Arch Phys Med Rehabil. 2010;91(9 suppl):S38–S43.
35. Hafiz A, Abbasi AN, Ali N, et al. Frequency and severity of acute toxicity of pelvic radiotherapy for gynecological cancer. J Coll Physicians Surg Pak. 2015;25:802–806.
36. Ballatori E, Roila F. Impact of nausea and vomiting on quality of life in cancer patients during chemotherapy. Health Qual Life Outcomes. 2003;1:46.
37. O'Gorman C, Denieffe S, Gooney M. Literature review: preoperative radiotherapy and rectal cancer - impact on acute symptom presentation and quality of life. J Clin Nurs. 2014;23:333–351.
38. Yucel B, Akkaş EA, Okur Y, et al. The impact of radiotherapy on quality of life for cancer patients: a longitudinal study. Support Care Cancer. 2014;22:2479–2487.
39. Fang P, Tan KS, Grover S, et al. Psychosocial encounters correlates with higher patient-reported functional quality of life in gynecological cancer patients receiving radiotherapy. Radiat Oncol. 2015;10:34.
40. Wiklund I, Tibblin G, Dimenäs G. Quality of life and hypertension. Where do we stand? New methods, new possibilities. Definitions and measurements of quality of life from a medical perspective. Scand J Prim Health Care. 1990;8:1–97.
41. Bruton A, Conway JH, Holgate ST. Reliability: what is it, and how is it measured? Physiotherapy. 2000;2:94–99.
42. Dunberger G, Thulin H, Waldenström AC, et al. Cancer survivors' perception of participation in a long-term follow-up study. J Med Ethics. 2013;39:41–45.
43. Roila F, Molassiotis A, Herrstedt J, et al. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol. 2016;27(suppl 5):v119–v133.
44. Kaat AJ, Schalet BD, Rutsohn J, et al. Physical function metric over measure: an illustration with the Patient-Reported Outcomes Measurement Information System (PROMIS) and the Functional Assessment of Cancer Therapy (FACT). Cancer. 2018;124:153–160.
45. Drott J, Vilhelmsson M, Kjellgren K, et al. Experiences with a self-reported mobile phone-based system among patients with colorectal cancer: a qualitative study. JMIR Mhealth Uhealth. 2016;4(2):e66.
Keywords:

Cancer care; Emesis; Methodology; Nausea questionnaire; Nursing theory; Oncology care; Patient-reported outcomes; Quality of life; Symptom documentation

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved