We compared PROs using LASA and PRO-CTCAE measures for breast cancer patients receiving radiation treatment in a prospective institutional registry. Our overall QOL LASA scores are consistent with other reports [11, 14]. This study supports the use of single item PROs, like LASA, for breast patients receiving radiation therapy. Patients who reported a PRO-CTCAE grade ≥ 3 (‘severe’ or worse) experienced statistically significant and clinically meaningful deterioration in overall QOL based on LASA scale. Additionally, BMI and hypofractionation impact overall QOL.
Our study supports the assertion that single item measures of QOL, like LASA, are useful in breast cancer and correlate well with PRO-CTCAE. Patients who reported grade ≥ 3 (‘severe’ or worse) PRO-CTCAE were found to have a 10-point drop in their overall QOL LASA score (p < 0.0001). As noted, a potential disadvantage of single-item measures, like LASA, is the lack of detail of the factors contributing to a decrease in quality of life [6]. The additional information provided from PRO-CTCAE can help clinicians identify the contributing factors of the decrease QOL that would not be available if LASA was used by itself. This also indicates that LASA may be useful as a screening tool. For example, all patients could be asked overall QOL LASA before each visit and if it indicates a worsening QOL then additional PRO measures like PRO-CTCAE could be used to better define the cause of the worsening QOL. This would help minimize the burden of long PRO questionnaires to patients while at the same time remaining useful for clinicians to improve patient care. Another concern is the potential for non-normal distribution of QOL using LASA including floor and ceiling effects. However, research has shown that the utilization of normal distribution theory is acceptable for Likert scale PROs even with floor/ceiling effects [15].
Hypofractionation has become a standard option for breast radiation therapy based on the results of several large randomized trials [16,17,18]. These trials have demonstrated less toxicity with hypofractionation compared to conventional fractionation [16, 17]. Additionally, hypofractionation is more cost effective compared to conventional fractionation [19]. As a result, the utilization of hypofractionation has become a standard and its use is increasing [20]. In keeping with this, the majority of patients in this study were treated with hypofractionation and were more likely to have better quality of life compared to women treated with conventional fractionation. This is similar to an analysis by Arsenault et al. who reported acute toxicity and PROs in a large randomized trial of conventional radiation versus hypofractionation following breast-conserving surgery for breast cancer [21]. A Breast Cancer Questionnaire, which is a validated instrument measuring quality of life in breast cancer patients, at baseline and 4 weeks after radiation was utilized. Patients randomized to hypofractionation had improved overall quality of life and quality of life attributed to less skin side effects, breast side effects, and improved attractiveness (all p < 0.01). Additionally, hypofractionated patients experienced less acute toxicity. Improved quality of life with hypofractionation in this study and ours furthers supports its use in the setting of breast cancer.
In the current study, higher BMI predicted for worse quality of life. Higher BMI has been shown to be associated with worse quality of life in other cancers [22, 23]. Similarly, higher BMI has also been shown to correlate to worse physician reported adverse events [24, 25]. In a study of breast cancer survivors, Anbari et al. used the validated 36-Item Short Form Health Survey to compare quality of life to changes in BMI which showed that a BMI change corresponded to 5 of the 8 domains [26]. However, increasing BMI corresponded to worsening quality of life in only 3 domains including physical functioning (p = 0.0052), role limitations related to emotional problems (p = 0.0216), and energy/fatigue (p = 0.0045). Interestingly, 2 domains, role limitations related to physical functioning and social functioning improved as BMI increased (p = 0.0052 and p = 0.0014, respectively). These studies suggest the relationship between a patient’s BMI and quality of life is complex and impacts quality of life during treatment and in survivorship. Additional research is needed to better define and explain the interaction.
Other studies have showed that single-item measures correlate well with multi-item measures [10, 27]. For example, Locke et al. investigated single-item LASA versus multi-item in patients with high grade gliomas [10]. Patients were assessed with LASA, the Functional Assessment of Cancer Therapy-Brain (FACT-Br), Profile of Mood States-Short form (POMS-SF), and Symptoms Distress Scale (SDS). They showed that LASA strongly correlated with each of the multi-item instruments and concluded that it might be useful as a screening measure with a general view of quality of life is needed. Similarly, Hubbard et al. performed a survey of providers after implementation of single-item LASA measures for fatigue, pain, and overall quality of life in clinical oncology practices [28]. The majority of providers in the study reported that the single-item measures enhanced their practice and did not change the length of clinic visits. The authors concluded that the study showed that single-item PROs measures can be used in oncology clinics with positive implications for patients and physicians.
This study has several limitations. First, although the LASA and PRO-CTCAE questionnaires were collected prospectively in an institutional registry, there was decreasing questionnaire responses over time. Part of this is likely due to patients being lost to follow-up and due to the extra burden of filling our questionnaires. Furthermore, additional follow-up is needed to evaluate how PROs evolve over time. The study is also subject to selection bias as to which patient filled out the questionnaires in follow up. It is possible that patients were more likely to fill out the questionnaires if they experienced worse outcomes. Lastly, this study was performed at a single academic institution, thus limiting its applicability to other practices.
In conclusion, in patients treated with curative intent radiation for breast cancer, the single-item LASA scale correlated well with PRO-CTCAE and supports the assertion that single-item overall QOL LASA could be used as a screening tool for PROs. Patients who reported a worsening PRO-CTCAE item to ‘severe’ or worse experienced statistically significant and clinically meaningful deterioration in overall QOL based on LASA. Hypofractionation appears to improve overall QOL while higher BMI predicted for worse QOL. These results contribute to the understanding of PRO-CTCAE for breast cancer patients and promote the value of integration of PRO-CTCAE items into future clinical trials.