Adaptive 3D Image-Guided Brachytherapy: A Strong Argument in the Debate on Systematic Radical Hysterectomy for Locally Advanced Cervical Cancer

Abstract

Purpose. To evaluate the outcomes of patients with locally advanced cervical cancer treated with three-dimensional image-guided brachytherapy (IGABT) after concomitant chemoradiation (CCRT). Materials and Methods. Data from patients treated with CCRT followed by magnetic resonance imaging-guided or computed tomography-guided pulsed-dose-rate brachytherapy, performed according to the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology guidelines, were reviewed. At first, stage I or II patients systematically underwent radical hysterectomy or were offered a randomized study evaluating hysterectomy. Then, hysterectomy was limited to salvage treatment. Results. Of 163 patients identified, 27% had stage IB, 57% had stage II, 12% had stage III, and 3% had stage IVA disease. The mean dose delivered (in 2-Gy dose equivalents) to 90% of the high-risk clinical target volume was 78.1 Ϯ 9.6 Gy, whereas the doses delivered to organs at risk were maintained under the usual thresholds. Sixty-one patients underwent a hysterectomy. Macroscopic residual disease was found in 13 cases. With a median follow-up of 36 months (range, 5-79 months), 45 patients had relapsed. The 3-year overall survival rate was 76%. Local and pelvic control rates were 92% and 86%, respectively. According to the Common Toxicity Criteria 3.0, 7.4% of patients experienced late grade 3 or 4 toxicity. Most of those had undergone postradiation radical surgery (2.9% vs. 14.8; p ϭ .005). Conclusion. IGABT combined with CCRT provides excellent locoregional control rates with low treatment-related morbidity, justifying the elimination of hysterectomy in the absence of obvious residual disease. Distant metastasis remains an important first relapse and may warrant more aggressive systemic treatment. The Oncologist 2013;18:415-422 Implications for Practice: Over the past 20 years, technical advances have led to dramatic changes in brachytherapy planning permitting three-dimensional image guidance and volume-based prescribing. Image-guided adaptive brachytherapy is about to become a gold standard in the treatment of locally advanced cervical cancer, pending the results of prospective studies. This series reports excellent locoregional control in patients treated with pulsed-dose rate brachytherapy following concomitant chemoradiation. Treatment-related morbidity was low, except in patients who underwent postradiation hysterectomy, justifying the abandon of hysterectomy in the absence of obvious residual disease. INTRODUCTIONThe treatment of patients with locally advanced cervical cancer (LACC) relies on a combination of concomitant chemoradiation (CCRT) and brachytherapy [1]. CCRT became the standard of care in 1999 with the publication of five randomized studies comparing chemoradiation with exclusive radiation therapy. A recent meta-analysis showed a 6% higher

Adaptive radiotherapy strategies for pelvic tumors – a systematic review of clinical implementations

“…In addition, a decrease in complications has been reported by patients receiving BT with ART in comparison with the old method of treatment delivery [27,29,37,38]. These encouraging results from following the Gynecological GEC-ESTRO recommendations [42,43] has also led to patients previously appointed to hysterectomy now being considered for BT [30]. Regarding the Beaumont trial, outcome was favorable or similar to the large non-ART trials using similar prescription delivered with 3DCRT [16,108,109,110] or IMRT [16,111,110] but toxicity was generally higher in the Beaumont trial [16,111,110].…”

“…Mature clinical outcome on recurrence and toxicity was reported by the gynecological cancers treated with a combination of EBRT and BT [23,[25][26][27][28][29][30][32][33][34][35][36][37][38][39] as well as from the large prostate trial conducted at Beaumont [12,[14][15][16]. For the gynecological cancers and most pronounced for the advanced stages, the improved target coverage obtained through ART has improved local control [37].…”

“…For gynecological tumor sites ART implementations had been used since 1993 for treatment of in total of 1409 patients at 10 institutions and one multi-center study (Table 3) [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]. All but four studies focused on cervical cancer, most commonly staged as FIGO IIB.…”

“…The BT was adapted through online re-planning prescribing different dose levels to each adapted risk volume and allowing an individual dose escalation bounded by the recommended OAR doses [42][43][44]. Twelve studies have so far reported their experience and outcomes after clinical implementation according to these recommendations (Table 3) [29][30][31][32][33][34][35][36][37][38][39][40], 10 of which focused solely on cervical cancer [29][30][31][34][35][36][37][38][39][40]. The majority (674/871) of the cervical cancer patients underwent EBRT combined with 1-3 fractions of pulsed-dose-rate (PDR) BT, 151 patients received EBRT and high-dose-rate (HDR) BT and 46 patients EBRT in addition to a combination of PDR and HDR (Table 3) [29][30][31][34][35][36][37][38][39][40].…”

Intrafractional organs movement in three-dimensional image-guided adaptive pulsed-dose-rate cervical cancer brachytherapy: Assessment and dosimetric impact

“…The procedure has been reported in detail elsewhere (5). Briefly, for each patient, a customized vaginal mold was created from a vaginal impression, containing one intrauterine and two vaginal catheters (6).…”