The present study examined primarily the impact of a patient-tailored IO program on adherence to palliative chemotherapy by patients with advanced gynecological cancer, as measured by RDI. It was shown that patients who were consistent in their attendance of the IO treatments were more likely to adhere (as reflected by an RDI of > 0.97) to the planned chemotherapy regimen than those who were non-consistent in IO care. However, this finding was specific for taxane and not for platinum-based regimens. The findings of the present study also suggest that in those cycles for which RDI was reduced (RDI < 0.97), adherence was better preserved with a percent decrease of 0.14 in group 1, compared to 0.23 in group 2.2 cycles.
The relationship between IO treatments and adherence to chemotherapy regimens may reflect the ability of the IO modalities to address QOL-related concerns, such as the reduction of taxane-induced peripheral neuropathy with acupuncture. The explanation for this relationship could be that by reducing adverse effects IO treatments would thereby increase the ability of patients to tolerate the agents being administered at the planned dose. Thus, these treatments would have less of an impact on RDI when the toxicity of the agent being administered is less QOL-related, as is the case for platinum-based regimens. The hypothesis that the impact of IO treatments on RDI is a direct result of their effectiveness in reducing symptoms and improving QOL, needs to be verified in future research of this setting.
The findings presented are similar to those of a previous study which also found a correlation between IO treatments and preserved RDI among patients with mixed breast and gynecological cancers undergoing adjuvant, neo-adjuvant, and palliative chemotherapy7. In contrast, the present study specifically examined only patients with advanced gynecological cancers undergoing palliative chemotherapy, and analyzed both 6-week chemotherapy cycles with or without concomitant IO treatments.
There are a number of limitations to the present study which need to be addressed before any conclusions can be reached from the findings. These include the pragmatic and non-randomized methodology, which in contrast to explanatory randomized controlled trials employed a preference-controlled design in which patients were able to choose whether or not they were to receive IO treatments during all of the chemotherapy cycles (i.e., Group 1); in some of these cycles (Group 2.1); or with no concomitant IO treatment in other cycles (Group 2.2). The study groups had different baseline oncology parameters, such as higher prevalence of ovarian cancer (vs. endometrial cancer) and metastatic disease in the non-consistent IO group. And while a preference bias may have been present, the data presented in Table 1 suggest that both study groups had, for the most part, similar baseline demographic and QOL-related parameter, as well as patient attitudes toward the role of complementary medicine.
Another significant study limitation is that the consistent IO group (group 1 in Table 2) may have had a less severe degree of disease, compared to the non-consistent group (group 2, Table 2). This was suggested by the higher rates of ovarian cancer in the latter group, though metastatic endometrial carcinoma has been shown to have lower 5-year survival rates than ovarian cancer (18% vs. 30%),. While the number of excluded patients due to disease progression/death was higher in the non-consistent group, as were the number of chemotherapy cycles analyzed, Table 1 shows that both groups shared similar QoL-related outcomes on EORTC and ESAS scales, as well as similar factors resulting in decreased RDI (Table 2).
It is possible, even likely, that the more severe degree of disease found in the non-consistent group may have negatively impacted the ability of patients to maintain total RDI, especially in Group 2.1 patients. Moreover, RDI within the two Group 2 subgroups (cycles with IO vs. cycles with no IO) was similar, requiring clarification through further research as to whether the IO-RDI association is specific to patients with highly advanced gynecological (i.e., stage IV ovarian) cancer. In addition, the present study did not assess QOL-related outcomes at the 6-week follow-up. Finally, the palliative care setting of the study is different from that of the neo-adjuvant/adjuvant chemotherapy setting. Here the patient's adherence to the planned chemotherapy protocol is most often determined by the disease progression and the use of additional oncology modalities (e.g., biological/immunological agents), together with or in lieu of chemotherapy drugs. In light of these limitations, the findings of the present study should be interpreted cautiously. Larger studies taking place in other oncology centers are needed to explore the generalizability and clinical significance of the present study's findings, this in real-world practice.
In conclusion, the present study suggests that a patient-tailored IO program for patients with advanced gynecological cancer may lead to a more preserved RDI effect at 6 weeks, specifically with taxane-based regimens. In contrast with the majority of IO-related research, which typically focuses on QoL-related outcomes, the present study suggests, despite its methodological limitations, that IO may also impact oncological parameters such as patients’ adherence to the planned chemotherapy protocol. Additional studies are needed to explore whether the association between adherence to IO and the oncology protocol is chemotherapy-specific, particularly in patients with advanced ovarian carcinoma. Further research should not only include randomized controlled trials but also qualitative research to explore patients’ and oncologists’ perspectives regarding the role of IO in increasing adherence to oncology treatment protocols.