Discussion
endometrial cancer, tumor, gastrointestinal symptoms, fatigue, gynecologic cancer, toxicity, cancer, impaired functioning, diarrhea, pain, constipation, gynecological malignancies, gynecological cancers, lymphedema, tumors, gynecological cancer
DISEASE PROGRESSION, ENDOMETRIAL CANCER, TUMOR, SENSORY NEUROPATHY, GYNECOLOGIC CANCER, CANCER, CERVICAL CANCER, LYMPHEDEMA, TUMORS
As oncologic outcomes for patients with cervical and endometrial cancer improve with the use of new diagnosis tools and advancements in imaging and therapeutics, the long-term side effects and quality of life for long-term survivors become all the more important. The prospective phase II APROVE trial analyzed the use of postoperative proton beam therapy for women with endometrial and cervical cancer in the adjuvant setting, aiming to establish a less toxic treatment method. Our study presented encouraging general and gynecologic-specific HRQOL, with improvements in patients’ perception of global quality of life and the maintenance of functioning performance 2 years after treatment.Multiple components of patient, tumor, treatment, social, psychological and physical characteristics contribute to changes in the quality of life of women with gynecologic cancer at diagnosis and during the course of interdisciplinary treatment. Our results in respect of the comparison of baseline values identified a high degree of impairment in several dimensions of HRQOL for our cancer cohort compared to the norm population. Our mean patient global health status at baseline was 58.0 and thus lower than those reported in cervical and endometrial cancer patients in previous studies, which ranged from 60.3 to 70.6 and partly declined during RT [The findings of prior studies on the post treatment changes of the remaining functional scales are also partly controversial. A prospective study of female gynecologic patients using photon RT by Greimel et al. [Two years after treatment, except for symptoms of fatigue, patients had not recovered from significant changes in impairments of pain, gastrointestinal symptoms and lymphedema, which diminished quality of life, even though patient-reported outcome assessments by physicians only determined low-grade toxicity. Previously reported studies of disease-free patients have observed impaired functioning after photon RT with a larger number of subscales, including higher rates of constipation, diarrhea and menopausal symptoms, which did not significantly lead to impaired quality of life after radiotherapy in our study [With respect to patient and treatment characteristics, the factors of age, the extent of surgical procedures, tumor stages and other potential factors did not significantly influence HQROL in our study. Contrary to this, intensified treatment concepts with the addition of photon chemoradiation have been shown to have a markedly negative impact on long-term HRQOL and sensory neuropathy in patients with endometrial cancer [Concerning sexual issues, the endometrial subgroup showed improved acute and long-term body image scores and a higher rate of sexual activity at the end of RT, which was not persistent after 24 months for the latter. Contrasting results which showed deterioration during and after the course of treatment have previously been described in women with cervical cancer, when radiotherapy was added to upfront surgery compared to surgery alone [However, the comparisons and conclusions made are mostly focused on the results of wide-spread photon therapy for the treatment of gynecologic cancers, while in the modern era, RT techniques are constantly improving, and the number of more cost-intense proton beam therapy facilities is increasing. In this context, RT techniques were previously reported to have a significant effect on overall quality of life in gynecological cancer patients as well as on functional and symptom scores changes after treatment completion, supporting the benefits of new image-guided intensity-modulated RT compared to 3D-conformal RT [The beneficial advantage of this theoretical proton dose escalation was reported in planning studies within tumors and extended fields with para-aortic lymph nodes [In clinical practice, only a few women (n = 7–11) with gynecological malignancies were reported to be treated with proton beam therapy, but the dosimetric results of statistically significant lower doses to the bowel, bladder and bone marrow are promising, and feasibility studies showed robust beam delivery [In this study, major limitations were caused by the small sample size and the study’s research design with the lack of a control group. Associations of the outcome after proton beam therapy must therefore be interpreted cautiously and further research with a photon radiotherapy control group is needed. Moreover, a partially limited questionnaire response rates might have restricted accurate assessment, especially in terms of sexual issues. Furthermore, patients with cervical and endometrial cancer were observed in one cohort. Even though they followed similar contouring guidelines and consecutively similar resulting planning target volumes, patients’ characteristics and biological responses may have differed. Subgroup analyses must be interpreted cautiously. Further, normative data for the German population is only available for the EORTC QLQ-C30 scales and missing for EN24 and CX24 questionnaires; thus, an age-matched comparison to assess the clinical impact for the latter does not exist and can only be estimated. Psychological effects caused by the application of a new, cost-intense RT method of proton beam therapy, which is not available to all patients, compared to the feeling of receiving standard-of-care photon therapy, can also not be completely ruled out. Concerning geometry-based treated volumes, the conventional CTV to PTV approach, as used in photon therapy, might not be completely applicable for proton beam therapy, in both treatment planning as well as plan evaluation, due to protons range uncertainties. Limitations of statistics include the risk of false-positive conclusion resulting from multiple testing in a small sample size without the use of conservative correction methods, which were not applied to avoid that any interesting correlation, that would be interesting to analyze in a larger phase III trial, may be disregarded. Further, the study protocol chose to censor participants at the time of disease progression instead of 3 months before as well as multiple institutional and standardized CTCAE version 4 symptom scoring systems, which might have led to misleading results.Nevertheless, proton beam therapy is increasingly implemented in the treatment of women with gynecological cancers and has great potential in administering lower doses to organs at risk and enhanced health recovery during follow-up. Our prospective study represents one of the first cohorts that highlight the impact of postoperative proton radiotherapy on the HRQOL of women with gynecological malignancies and suggests novel, promising results regarding the maintenance of overall quality of life and the impact of only low-grade toxicity. However, to provide adequate health information and patient selection, and for a better understanding of the impact, characterization and treatment of impairments of HRQOL, larger and randomized trials are needed to further confirm the translation of the benefits of proton beam therapy into clinical effects.