«Patterns of sore mouth in outpatients with cancer receiving chemotherapy. By: Carlton G. Brown, Susan L. Beck, Douglas E. Peterson, Deborah B. ...»
Identifying specific individual patterns. All graphs were examined to discover any commonalities and differences in the 21-day trajectories of a SM. The word intensity was used to refer to the degree of severity or distress reported. Seven patterns were identified: early Onset (between days 1 and 5); middle onset (between days 6 and 9); late onset (beginning on or after day 10); onset intensity (first response greater than a 5 on 1–10 scale); duration intensity (after day 15 and a SM score equal to or greater than a 5 on a 1–10 scale); late duration (continuing after day 15); and low intensity (no response greater than 4 on a 1–10 scale). Once the patterns were determined, the individual graphs were visually sorted into these seven pattern groups and labeled. It was possible for any single graph to be categorized into more than one pattern group.
Performing validation and verification. Members of the research team reviewed and independently verified coding of each graph. When differences occurred, they were discussed until a consensus was reached.
Data analysis Data analysis was performed using SPSS (version 11). Multiple analyses using cross-tabulations with chi-square tests were conducted to evaluate whether any differences in demographic or clinical characteristics existed among individuals categorized into each of the seven pattern groups. We collapsed categories to improve the power of the chi-square analyses as appropriate and meaningful, and cell sizes were adequate for the total number of cells included (i.e., at least five per cell). However, in some instances (e.g., type of chemotherapy), inclusion of specific categories was most meaningful even if there were less than five cases in some cells. We recognized that findings are not definitive but may inform future studies The three onset patterns were combined into a new variable called onset that consisted of three levels (early, middle, and late onset). The other pattern variables (onset intensity, duration intensity, late duration, and low intensity) consisted of two levels, either “yes” (for those assigned to the pattern) or “no” (for those not assigned to the pattern). Demographic variables were collapsed in order to have adequate cell sizes to conduct chi-square tests as follows: gender (male or female), marital status (married or non-married), educational level (high school or college), and income level (0–39,999or40,000 and above). Treatment variables included type of cancer (breast, non-Hodgkin’s lymphoma, or other cancers) and type of chemotherapy [doxorubicin and cyclophosphamide (AC); cyclophosphamide, methotrexate, and flurouracil (CMF); rituximab plus cyclophosphamide, oncovin, doxirubicin, and prednisone (R-CHOP); and other chemotherapies]. An independent-samples t test was conducted to evaluate whether there was a difference in age between those who were and who were not assigned to a certain onset pattern group. Since the variable of onset had three levels (early, middle, and late), analysis of variance (ANOVA) was used to determine differences in age.
Of the 223 study participants, 115 (51%) reported SM at any point in time. Of the 115 patients reporting SM, 51 participants reported three or more days of SM in either the second (n = 45) or third (n = 29) cycle of chemotherapy, yielding74 graphs for analysis. The demographic and clinical characteristics of participants with SM are presented in Table 2. The majority of the participants were female (n = 41, 82%) with a mean age of 53 years (SD = 8.35). Most were married (68%), with a diagnosis of breast cancer (68%), and receiving chemotherapy of AC (33.3%). Approximately 30% of the participants had some college or trade school education, and approximately 40% reported earning more than $70,000 per year.
Table 2 Characteristics of participants reporting SM (n = 51)
Aim 1 was to explore and categorize patterns in the development, duration, intensity, and resolution of SM severity and distress over two cycles of chemotherapy in cancer outpatients. By using VGA, plots were categorized into the seven patterns mentioned earlier: early onset (n = 17;
see Fig. 1); middle onset (n = 43; see Fig. 2); late onset (n = 14; see Fig. 3); onset intensity (n = 6;
Fig. 4); duration intensity (n = 13; see Fig. 5); late duration (n = 19; see Fig. 6); and low intensity (n = 36; see Fig. 7). As noted previously, every participant was sorted into one of the levels of onset (early, middle, and late) and then into any of the other pattern groups that appeared to apply to the data (onset intensity, duration intensity, late duration, or low intensity).
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A small group of patients (n = 14) presented a pattern of two episodes of SM severity occurring during one cycle of chemotherapy separated by at least 2 days of no SM (see Fig. 8). Because some of the patients reported SM at the onset of a cycle and then again at least 2 days later in the cycle, dates at the end of cycle 2 and the beginning of cycle 3 were verified to ensure that the two episodes were indeed in the same cycle.
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VGA analysis of SM distress revealed that in virtually every case, SM distress scores were very similar to those for SM severity (see Fig. 9). Equivalence was verified by computing a daily difference score between severity and distress. Interestingly, of the 1,007 daily difference scores, 97% of the severity and distress scores differed by one or less. Thus, patterns of distress and severity were judged as equivalent.
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Aim 2 was to describe and explore the relationship of demographic (age, gender, marital status, and educational level) and disease characteristics (type of cancer and type of chemotherapy) to specific SM patterns. Table 3 presents the statistical results (χ 2 and t) and the significance of relationships between participants’ characteristics and patterns of SM. Similar to the patients who reported SM, those patients who did not report SM were mostly female (78%) with a mean age of 57.8 years (SD = 12.18). The majority of them were Caucasian (92%), married (75%), with a diagnosis of breast cancer (33%), and received AC as treatment.
Table 3 Statistical results (χ 2 and t) and significance of relationships between participant characteristics and patterns of SM (n = 74)
Onset Table 4 presents the relationship between the significant variables (marital status and chemotherapy type) and the pattern of onset of SM. There was a significant association between marital status coded as married versus not married [single, divorced, or widowed; χ 2(2) = 7.08, p = 0.03]. The strength of the relationship between married and non-married was low (Φ = 0.32), although the nature of the association as indicated by adjusted residuals  suggested that nonmarried individuals tended to show early onset more often than married individuals. The results of the chi-square analysis indicated a statistically significant but weak association between those in the early, medium, and late onset and the chemotherapy type they received [χ 2(4) = 24.86, p = 0.002, Cramer’s V = 0.42]. An examination of standardized residuals  suggested that patients who received AC (3.7) were more likely to experience late onset SM. Patients who received CMF (2.6) experienced middle onset, and patients who received some of the “other” drugs (2.6) were more likely to experience early onset. There were no significant differences between these three groups (early, middle, and late onset) in gender, educational level, and type of cancer. Further, an ANOVA showed there was no significant difference in age [F(2,67) = 2.43, p = 0.10] between the three levels of onset.
Table 4 Percentages and adjusted residuals of marital status and chemotherapy type and pattern of onset of SM
a Significant adjusted residuals the absolute value of 2 Onset intensity Table 5 summarizes the relationships among cancer type, chemotherapy administered, and patterns of SM for onset intensity, duration intensity, late duration, and low intensity. There were no significant differences between those in the onset intensity group and those who were not in the group on marital status, gender, age, income, or educational level. However, a chi-square analysis revealed a statistically significant but weak association between those patients in the onset intensity group and those not in it in terms of cancer diagnosis [χ 2(2) = 9.48, p = 0.009, Cramer’s V = 0.37]. An examination of standardized residuals suggested that patients with nonHodgkin’s lymphoma (NHL, −3.1) were significantly less likely to be sorted into the onset intensity group. There was a significant association in these two onset intensity groups in terms of the chemotherapy they received [χ 2(2) = 16.00, p = 0.003, Cramer’s V = 0.48]. Those receiving R-CHOP seem to have a different pattern and may be more likely to have onset intensity than women with breast cancer. None of these R-CHOP patients were in the low intensity group. These results must be viewed as tentative because of the number of cells with less than five, which violates the assumption of the analysis.
Table 5 Percentages and adjusted residuals for cancer type and chemotherapy administered and patterns of SM
a Residual presented as absolute value b Significant adjusted residuals 2 Duration intensity There were no significant differences between those in the duration intensity group and those who were not on gender, age, marital status, educational level, or income level. There were statistically significant yet weak differences between these two groups in terms of cancer diagnosis [χ 2(2) = 9.10, p = 0.011, Cramer’s V = 0.36] and chemotherapy [χ 2(4) = 12.27, p = 0.015, Cramer’s V = 0.41]. Interestingly, patients with “other” cancers were never sorted into the group that experienced duration intensity. Patients who received R-CHOP (3.2) were significantly more likely to experience duration intensity, but not those patients who received AC (0.5).
There were no significant differences between those in the late duration group and those who were not on gender, age, marital status, educational level, income level, and type of chemotherapy administered. There was a statistically significant yet weak association between the late duration and the non-late-duration groups on the type of cancer diagnosis [χ 2(2) = 6.42, p = 0.040, Cramer’s V = 0.30]. Adjusted residuals showed that those patients in the “other” cancer group (2.3) were significantly less likely to experience late duration. In fact, only one patient who experienced late duration had an “other” cancer diagnosis.
Chi-square analysis revealed a statistically significant yet weak association between those patients in the low intensity group and those not in it in terms of cancer diagnosis [χ 2(2) = 7.57, p = 0.023, Cramer’s V = 0.33]. Examination of standardized residuals suggested that patients who were in the “other” cancer diagnosis group (2.6) were significantly more likely to experience low intensity SM. There were no significant differences between those in the low intensity group and those not in it on gender, age, marital status, educational level, income level, and type of chemotherapy administered.
In summary, there were statistically significant differences between the three onset groups by marital status, as non-married patients were more likely to report onset earlier than married patients. Concerning the type of cancer, patients with “other” cancers tended to experience a SM with lower intensity and without duration intensity and/or late duration. Patients with NHL did not experience a SM associated with onset intensity. Concerning the type of chemotherapy administered and patterns of a SM, the following associations between type of chemotherapy and
SM patterns were noted:
• AC was significantly associated with late onset, but not duration intensity.
• R-CHOP was significantly associated with duration intensity.
• CMF was significantly associated with middle onset.
• “Other” chemotherapy drugs (fluorouracil, cisplatin) were associated with early onset.
Sore mouth longitudinal daily mean scores Although mean scores may hide the individual patterns of sore mouth, these data are presented in Fig. 10. Very few studies have presented daily sore mouth severity scores in outpatient populations receiving chemotherapy.
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Discussion Results from this study demonstrated that cancer patients receiving outpatient chemotherapy experience several different patterns of SM severity and distress. A majority of patients (n = 43) experienced middle onset SM occurring sometime between days 6 and 9. This middle onset pattern is commonly witnessed in clinical practice, yet is later than the days 4 to 5 onset that is suggested in the clinical literature. Moreover, middle onset was not the only onset pattern. Some patients reported the early onset of SM within 1–3 days after receiving chemotherapy treatment.
Other patients reported a late onset of SM in which the first incidence of SM was not reported until day 10 or later. These findings of early and late onset challenge the usual clinical assumption and observations that most acute mucosal injuries induced by chemotherapy develop within 1 week of drug administration (usually by day 4 or 5) and peaks within 2 weeks . It is likely that these two patterns of onset would have been missed if intermittent measurements common in clinical practice (such as the beginning of chemotherapy and maybe the nadir) and traditional summary statistics were used to conduct the data analysis.