Image-Guided Brachytherapy for Salvage Reirradiation: A Systematic Review

Abstract

Background: Local recurrence in gynecological malignancies occurring in a previously irradiated field is a challenging clinical issue. The most frequent curative-intent treatment is salvage surgery. Reirradiation, using three-dimensional image-guided brachytherapy (3D-IGBT), might be a suitable alternative. We reviewed recent literature concerning 3D-IGBT for reirradiation in the context of local recurrences from gynecological malignancies.

Methods: We conducted a large-scale literature research, and 15 original studies, responding to our research criteria, were finally selected.

Results: Local control rates ranged from 44% to 71.4% at 2-5 years, and overall survival rates ranged from 39.5% to 78% at 2-5 years. Grade ≥3 toxicities ranged from 1.7% to 50%, with only one study reporting a grade 5 event. Results in terms of outcome and toxicities were highly variable depending on studies. Several studies suggested that local control could be improved with 2 Gy equivalent doses >40 Gy.

Conclusion: IGBT appears to be a feasible alternative to salvage surgery in inoperable patients or patients refusing surgery, with an acceptable outcome for patients who have no other curative therapeutic options, however at a high cost of long-term grade ≥3 toxicities in some studies. We recommend that patients with local recurrence from gynecologic neoplasm occurring in previously irradiated fields should be referred to highly experienced expert centers. Centralization of data and large-scale multicentric international prospective trials are warranted. Efforts should be made to improve local control while limiting the risk of toxicities.

Keywords: brachytherapy; cervical cancer; endometrial cancer; gynecologic cancer; radiotherapy; reirradiation; vaginal cancer; vulvar cancer.

Figure 1

Data selection process: Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) flow diagram.

Figure 2

Example of MRI-guided PDR BT reirradiation for vulvo vaginal recurrence. (A) MRI-guided PDR BT reirradiation implant to a 6 cm vulvo-vaginal recurrence of cervical epidermoid carcinoma, initially treated in another center with pelvic EBRT (45 Gy in 25 fractions) followed by HDR BT (25 Gy in 5 fractions of 5 Gy). Because of the size (>3 cm) of the vaginal recurrence, the patient was treated first by pelvic EBRT (39.6 Gy in 22 fractions of 1.8 Gy in the tumor, and 45 Gy in 25 fractions of 1.8 Gy in inguinal lymph nodes), followed by an MRI-guided PDR BT with vaginal mold associated with free-hand needles, at the dose of 20.10 Gy in 67 pulses of 0.30 Gy. The EQD2 reirradiation doses (EBRT + BT) were the following: HR-CTV D₉₀ = 67.42 Gy, bladder D2cc = 42.73 Gy, rectum D2cc = 60.57 Gy, sigmoid D2cc = 39.47 Gy, and small bowel D2cc = 39.11 Gy. (B) Pelvic MRI showing the vulvo-vaginal recurrence before re-RT (left), and a complete response 8 weeks after MRI-guided PDT BT (right).

Figure 3

Example of MRI-guided PDR BT reirradiation for vaginal recurrence. MRI-guided PDR BT reirradiation implant to a bi-focal recurrence of endometrial adenocarcinoma to the lower third of the vagina, initially treated by total hysterectomy, followed by pelvic EBRT (45 Gy in 25 fractions) and by HDR BT of vaginal cuff (10 Gy in 2 weekly fractions of 5 Gy). Because of the bi-focality of the vaginal recurrence, the patient was treated first by vaginal EBRT (30.6 Gy in 17 fractions of 1.8 Gy), followed by MRI-guided PDR BT with vaginal mold associated with free-hand needles, at the dose of 30 Gy in 100 pulses of 0.30 Gy. The EQD2 reirradiation doses (EBRT + BT) were the following: HR-CTV D₉₀ = 73.19 Gy, bladder D2cc = 39.76 Gy, rectum D2cc = 43.85 Gy, sigmoid D2cc = 32.98 Gy, and small bowel D2cc = 31.97 Gy.