Targeted Radiotherapy Using Contact X-ray Brachytherapy 50 kV

Abstract

Rectal adenocarcinoma is a quite radioresistant tumor. In order to achieve non-operative management (NOM) radiotherapy plays a major role. Targeted radiotherapy aiming at high precision 3D radiotherapy uses stereotactic image-guided external beam radiotherapy machines. To further safely increase the tumor dose, endocavitary brachytherapy (ECB) is an original approach. There are two different ways to perform such an ECB: contact X-ray brachytherapy (CXB) using a 50 kV X-ray generator with an X-ray tube positioned under eye guidance into the rectal cavity and high-dose-rate brachytherapy (HDRB) using iridium-192 sources positioned into the rectal cavity under image guidance. This study focused on CXB. CXB uses a small mobile generator that produces 50 kV X-rays with limited penetration. This technique is well adapted to accessible tumors of limited size and especially needs a high dose rate (≥15 Gy/minutes) for rectal tumors. It is performed on an ambulatory basis. A total dose between 80–110 Gy is delivered in 3–4 fractions over 3 to 6 weeks into a small volume (5 cm3). CXB was pioneered in the 1970s by Papillon using the Philips RT 50TM. Since 2009, the Papillon P50TM has been used in 11 institutions in Europe. The OPERA Phase III trial tested the hypothesis that a CXB boost (90 Gy/3 fr) compared to an EBRT boost (9 Gy/5 fr) for T2–T3 ab < 5 cm and N0–N1 < 8 mm will increase the 3-year organ preservation (OP) rate when combined with 45 Gy/5 weeks with concomitant capecitabine. Out of more than 300 patients with tumors < 3 cm (1962–1992), Papillon reported a long-term local control close to 85%. Similar results were published in Europe and USA at that time. The Lyon R96-2 Phase III trial (2004) demonstrated that, when combined with preoperative EBRT, a CXB boost (90 Gy/3 fr) significantly increased the rate of clinical complete response (cCR) and sphincter preservation, with some patients having OP at 10 years. With more than 2000 patients treated in Europe (2010–2020) using the Papillon 50TM, organ preservation appears possible in close to 80% of cases in selected early T2–T3. The OPERA trial closed after 141 inclusions (2015–2020) after an independent data monitoring committee recommendation because of promising results. At the 2-year follow-up (blinded data), the rate of cCR and OP were 77% and 72%, respectively, for the 141 tumors, and for T < 3 cm (61 pts), they were 86% and 85%, respectively, with good bowel function. The final results should be available in 2022. Organ preservation using NOM appears to be a promising approach for rectal cancer. A CXB boost with chemoradiotherapy in selected early T2–T3 could become an attractive option to achieve a planned OP. This approach should be proposed to well-informed patients after discussion in an MDT.

Features on Endoscopy and MRI after Treatment with Contact X-ray Brachytherapy for Rectal Cancer: Explorative Results

“…Of the 36 patients treated with CXB following neoadjuvant (chemo)radiotherapy in the present study, 21 patients (51%) did not develop a cCR and had a residual tumor following CXB. In light of the recently published data of the OPERA trial [ 21 , 22 ], reporting a 3-year organ-preserving rate of 81%, the oncological results of the present study are modest. This difference can partly be explained by the difference in selection criteria for CXB.…”

“…However, higher complete response rates were observed with an increasing interval up to 16 weeks after neoadjuvant (chemo)radiotherapy [ 24 , 25 , 26 ]. As such, performing CXB according to the treatment schedule of the OPERA trial, irrespectively of the tumor response following a 2–3-week interval after neoadjuvant (chemo)radiotherapy, may result in overtreatment in a substantial number of patients who may continue on to a cCR following conventional (chemo)radiotherapy only [ 21 ]. Due to advancing insight and the results of the present study, the authors nowadays use more strict selection criteria for treatment with CXB aiming at organ preservation, where patients with a residual tumor of more than 3 cm and/or an interval of more than 3 months after (chemo)radiotherapy are generally no longer considered for CXB, in accordance with the ESTRO consensus recommendations for CXB [ 27 ].…”

Validated Pretreatment Prediction Models for Response to Neoadjuvant Therapy in Patients with Rectal Cancer: A Systematic Review and Critical Appraisal

“…Patients with a cCR can be offered a "watch and wait" (W&W) strategy to avoid major surgery. Some patients with a near-cCR (ncCR) can be treated with additional treatment to avoid TME, such as local excision or contact X-ray brachytherapy (Papillion) [10][11][12], followed by a W&W approach if a complete response is achieved. Accumulating evidence shows that a W&W strategy might be considered as a safe alternative to TME surgery [6,[13][14][15].…”