Hypofractionated Radiotherapy in Gynecologic Malignancies-A Peek into the Upcoming Evidence

Abstract

Radiotherapy (RT) has a fundamental role in the treatment of gynecologic malignancies, including cervical and uterine cancers. Hypofractionated RT has gained popularity in many cancer sites, boosted by technological advances in treatment delivery and image verification. Hypofractionated RT uptake was intensified during the COVID-19 pandemic and has the potential to improve universal access to radiotherapy worldwide, especially in low-resource settings. This review summarizes the rationale, the current challenges and investigation efforts, together with the recent developments associated with hypofractionated RT in gynecologic malignancies. A comprehensive search was undertaken using multiple databases and ongoing trial registries. In the definitive radiotherapy setting for cervical cancers, there are several ongoing clinical trials from Canada, Mexico, Iran, the Philippines and Thailand investigating the role of a moderate hypofractionated external beam RT regimen in the low-risk locally advanced population. Likewise, there are ongoing ultra and moderate hypofractionated RT trials in the uterine cancer setting. One Canadian prospective trial of stereotactic hypofractionated adjuvant RT for uterine cancer patients suggested a good tolerance to this treatment strategy in the acute setting, with a follow-up trial currently randomizing patients between conventional fractionation and the hypofractionated dose regimen delivered in the former trial. Although not yet ready for prime-time use, hypofractionated RT could be a potential solution to several challenges that limit access to and the utilization of radiotherapy for gynecologic cancer patients worldwide.

Keywords: cervical cancer; gynecologic malignancies; hypofractionated radiotherapy; universal access to radiotherapy; uterine cancer.

Figure 1

Schema of a typical external beam radiotherapy (EBRT) course using conventional fractionation in gynecologic malignancies with 25 fractions delivered daily over 5 weeks (top, in black). This fractionation is typically seen in radical EBRT treatments of locally advanced cervical cancers or in the adjuvant setting of endometrial cancer, post-hysterectomy. The role of a moderately hypofractionated course with 15 daily fractions is under investigation in randomized phase 2 trials involving cervical cancer patients (middle, in blue). The role of ultrafractionated regimes with five fractions delivered every other day is currently being investigated in a phase 2 randomized trial in the adjuvant endometrial cancer setting (bottom, in green).

Figure 2

Axial and sagittal images of a hypofractionated treatment plan delivered to a patient enrolled in the HEROICC clinical trial. Note the simultaneous integrated boost (SIB) to the right external iliac enlarged lymph node with a prescription dose of 46 Gy outlined in red (red arrow) while the remaining pelvis is covered by the 95% prescription isodose line (relative to 40 Gy) outlined in green (green arrow). The prescription dose of 40 Gy runs tightly around CTVs (orange arrow).

Figure 3

Axial and sagittal images of an SBRT treatment plan delivered to a patient enrolled in the SPARTACUS clinical trial. Note the conformality of the 95% prescription isodose line (yellow arrow) outlined in yellow around PTV volumes (in dark blue) and the homogenous dose distribution within treated volumes with absence of pockets of 105% isodose lines (blue arrow).