IGABT of gynaecological cancer is based on individualization of dose distribution to the 3D changes of tumour and organs at risk (OAR) over the fourth dimension - time, and fifth dimension of risk-continuum. The risk-continuum refers to the antagonistic probabilities of tumour recurrence and side effects as a function of tissue volume, exposed to dose. In this context, IGABT capitalizes on the regression of the primary tumour during treatment to maximize the ratio between cure and complication probabilities.
These principles are reflected in excellent results of gynaecological IGABT with major improvement of cure rates without increased morbidity when compared with the conventional results of point A - based BT. As more patients enter long-term survivorship, systematic recording and treatment of IGABT-related side effects becomes increasingly important. In this regard, the proactive approach, aiming to minimize the probability of late complications, cannot be overemphad. Central to this concept are good application technique, quality assurance, and evidence-based planning aims and dose constraints.
Several publications, particularly the retro-EMBRACE and EMBRACE 1 studies provide clinical evidence to establish dose-volume-effect relationships for various OAR and endpoints. The level of reliability for these relationships ranges among OAR from high (bladder, rectum, bowel, vagina) to intermediate (ureters) and low (sigmoid colon, anal canal). Relationships between dose exposure and non-specific endpoints including fatigue/insomnia and risk factors for lymph oedema have been established as well. In summary, the accumulated evidence supports the use of selected treatment planning principles and dose constraints for the OAR in clinical practice and future research.
For a better insight regarding the burden of late side effects among cervix cancer survivors, crude prevalence of organ-associated morbidity should be considered as well. The rates of crude prevalence for EMBRACE I study were approximately 3 times lower than the actuarial incidence. Furthermore, some patients with side effects do not suffer the symptoms persistently over time, due to their inherent fluctuation or successful treatment. Therefore, a longitudinal method for assessment of Late Persistent Substantial treatment-related symptoms (LAPERS) has been developed to identify the rates of clinically relevant chronic symptoms. The evidence suggests that the proportion of patients with LAPERS events is lower than crude prevalence rates. Finally, the subjective experience of objectively similar events may vary among survivors. The patient’s private and professional characteristics, spiritual orientations, general beliefs, value systems, socioeconomic situation, psychologic profile, and other factors all play into the individual experience of side effects and their assessment as the “cost” of long-term cure. In this context, the importance of patient participation during dose-volume-risk assessment and the use of patient-reported outcome measures (PROMs) to monitor post-treatment side effects in clinical practice and studies cannot be overemphad.
In patients with LAPERS events after radiotherapy, treatment options vary depending on the OAR and symptoms, severity of complaints, medical situation, and patient preference. I will offer an overview of the preventative and therapeutic strategies to address this increasingly important aspect of care for the long-term survivors after IGABT of gynecologic malignancies.