Adverse events from systemic treatment of cancer and patient-reported quality of life

Discussion

The findings in this study show that impact on QoL imagined by members of the general public is higher than that declared by cancer patients who have experienced the AEs. It is worth noting that that result was observed for all 10 toxic events, thus confirming the investigational hypothesis of the study. However, the graph shows a strong parallel between the 2 groups, which means that both populations similarly perceive upward and downward variations in the impact resulting from the different toxic events (Figure).

Three previous studies have addressed the comparison of the impact of different AEs in these 2 populations and findings from all 3 showed the same systematic difference between patients and the general public participants. The first, Calhoun and colleagues used time to trade-off (TTO, a measure of the QoL a person or groups is experiencing) to compare therapies for ovarian cancer in patients and the general population (n = 39 for each group). The results showed that cancer patients valued more the health status associated with toxicity than did the general public participants.¹³ The design of the second study, by Havrilesky and colleagues, was similar to that of the present study, and they compared toxic events one by one, using VAS and TTO in 13 ovarian cancer patients and 37 women of the general public.¹⁴ The investigators found the same results as we did on the parallel of the 2 groups and also a very similar order of the toxic events. Indeed, alopecia was the less bothersome, whereas both motor neuropathy and severe vomiting were among the worst toxic events. Therefore, our results correlate perfectly with theirs. Best and colleagues found that health states values associated with oxaliplatin-related peripheral neuropathy were lower in the general public population compared with those of cancer patients.¹⁵ Besides adaptive behavior of the patients, all these results may be explained by an established awareness cancer patients have of the dual outcome of cancer treatments (AEs and benefits from the treatment).⁹ This awareness is absent in the general public participants, who can only envision the negative outcomes and who do not realize the importance of the benefits.⁹ Findings from previous studies conducted in several tumor types such as breast cancer^16-18 non–small-cell lung cancer,¹⁹ thyroid cancer,²⁰ and renal cancer²¹ have shown that patients are willing to trade-off AEs for treatment benefits.

Alopecia has been considered as one of the most distressing and troublesome AEs of cancer therapy.²² However, in the present study, alopecia was rated inside the range of mild toxic events as it is in the study by Havrilesky and colleagues.¹⁴ Our results show that alopecia was placed as the first less damaging toxic event when assessed with the EQ-5D-5L, the second less damaging when assessed with a rank-order system, and the third less damaging when assessed the VAS. This could be related to current fashion trends that promote shaving one’s hair, which minimizes the social stigma of alopecia and its association with cancer treatment.

The other esthetic event we analyzed was acneiform rash associated with anti-EGFR agents. Our results show that severe rash was rated as clearly worse than alopecia by the 2 populations, irrespective of the measuring instrument (VAS, EQ-5D-5L, or ordinal assessment). To our knowledge, the present study is the first to demonstrate the relative impact of total alopecia and severe rash on patient QoL. This result is even more significant considering that we included grade 2 acneiform rash inside the Severe Rash toxic event. Our results show that the worst AEs for both populations were severe vomiting and neurotoxicity with functional impairment. The high impact of severe vomiting, the quintessentially chemotherapy-induced AE, was to be expected because it is strongly supported by a number of previous reports,^14,23 as is also true for peripheral motor neuropathy.^14,15,24

EQ-5D is a powerful instrument for measuring health status²⁵ and is widely used to describe and evaluate patient health.²⁶ Our results from the 5 dimensions represented by a single score were well correlated with the results of the VAS. However, whereas median VAS scores were evenly distributed in the 0-100 range of the VAS, median EQ-5D-5L scores were distributed mainly in the 0.5-1.0 range (full range, -0.654-1.000, for Spanish population).

The final single score of the original EQ-5D is based on responses from the general public, and we have shown that its use is a valid option when the objective is the evaluation of AEs in patients with cancer. Management of AEs is of the utmost importance in this era of personalized cancer medicine. Basch and colleagues recently reported that an intensive web-based follow-up of AEs during chemotherapy improved overall survival compared with standard follow-up.²⁷ The results of our study show that patients have strongly defined preferences regarding AEs. Therefore, therapeutic strategies with a personalized approach in managing AEs would be associated with increased effectiveness.

There are some limitations in the present study. First, we modified slightly the EQ-5D-5L questionnaire by asking patients to recall and rate the days they experienced the adverse event instead of asking for “today’s feelings.” It is not known how this modification affects internal validity of this study. Second, we asked patients to isolate the toxic event to rate it independently from the other toxic events. We believe that this request may have been difficult for some patients to do because they might have experienced more than 1 toxic event concurrently. Third, using VAS to assess health status may be a weakness because it has been considered to be too straightforward an instrument. Likewise, there are some strengths of the study: it was performed in a face-to-face manner; it displayed cardinal and ordinal results for participants in the public group; and the results are the same as those in a previous study.¹⁴

In conclusion, patients with cancer who have experienced AEs perceive a lower impact on their QoL compared with that envisioned by participants from the general public. The EQ-5D-5L is a useful tool for evaluating cancer-therapy–related AEs. The impact of alopecia on QoL was notably low and even lower than that of severe rash. Further investigation on this issue should focus on patients’ and oncologists’ shared choices, which increasingly will be driven by patient preferences.