A multi-centre analysis of adjuvant contact X-ray brachytherapy (CXB) in rectal cancer patients treated with local excision - Preliminary results of the CONTEM1 study.

Early rectal cancers are increasingly diagnosed through screening programmes and are often treated using local excision (LE). In the case of adverse pathological features completion total mesorectal excision surgery (TME) is the standard recommendation. The morbidity and mortality risks of TME have stimulated the use of adjunctive treatments following LE to achieve organ preservation. Patients treated with adjuvant CXB following local excision between 2004 and 2017 in three centres were identified (Clatterbridge, Hull, Nice). All patients had adverse pathological features including: lymphovacular invasion, Sm2-3 Kikuchi level, tumour budding, pT2, positive resection margins (R1). CXB was performed with the Papillon50 tm machine to a dose of 40-60 Gy in 2 or 3 fractions over 2-4 weeks preceding/following external beam chemo/radiotherapy. Kaplan Meier survival estimates were used for outcomes measures. 194 patients were identified. Median age was 70 years. pT staging was: pT1:143, pT2:45, pT3:6. CXB alone was given in 24 pts and combined with EBRT in 170. Median follow-up time was 77 months (range 7-122 months). Local relapse rate was 8% and distant metastases 9%. Organ preservation was achieved in 95%. 6 year local recurrence free and overall survival was 91% and 81% respectively. Cancer specific survival was 97%. No treatment related mortality was seen. This large multi-centre cohort study using adjuvant CXB following local excision suggests excellent oncological outcomes for these patients without completion TME. This treatment approach can be considered as an alternative for selective patients compliant with long term follow up.

Dhadda A ，Sun Myint A ，Thamphya B ，Hunter I ，Hershman M ，Gerard JP ... -  《-》

Organ or sphincter preservation for rectal cancer. The role of contact X-ray brachytherapy in a monocentric series of 112 patients.

Contact X-ray brachytherapy (CXB) has been used at Centre Antoine Lacassagne since 2002 to increase the chance of conservative treatment (organ or sphincter preservation) in rectal cancer. A consecutive series of 112 patients (pts) is reported. Three protocols were used in selected rectal adenocarcinomas. Group 1: T1 N0 treated with local excision (LE) followed by adjuvant CXB. Group 2: T2 or 'early' T3 N0 treated with CXB combined with chemoradiotherapy (CRT) followed by surveillance or LE. Group 3: distal 'locally advanced' T3 N0-2 treated with CXB and CRT before total proctectomy. Group 1: 27 pt (pTis: 3; pT1: 21; pT2: 3). After LE with CXB alone (20 pt) or CXB + CRT (7 pt) one local recurrence occurred. Organ preservation was achieved in 26 pt (96%). Group 2: 45 pt (T1: 2; T2: 23; T3: 20) treated with CXB alone (4 pt) or CXB + CRT or external beam radiotherapy (EBRT) (41 pt). A clinical complete response (cCR) was observed in 43/45 (96%) and 3 pt developed a local recurrence (11% at 5 years). The specific survival was 76% at 5 years and the rate of organ preservation was 89% (40/45 pt) with good bowel function in 36 pt. Group 3: 40 pt, anterior resection (with sphincter preservation) was possible in 35 pt (86%) with a 3-year local recurrence of 6%. CXB usually combined as a boost with CRT or EBRT may safely increase the chance of a conservative treatment (organ or sphincter preservation) for selected rectal cancers.

Frin AC ，Evesque L ，Gal J ，Benezery K ，François E ，Gugenheim J ，Benizri E ，Château Y ，Marcié S ，Doyen J ，Gérard JP ... -  《-》

The safety and efficacy of total mesorectal excision (TME) surgery following dose-escalation: Surgical outcomes from the organ preservation in early rectal adenocarcinoma (OPERA) trial, a European multicentre phase 3 randomised trial (NCT02505750).

Nonsurgical treatment with chemoradiotherapy for rectal cancer is gaining interest as it avoids total mesorectal excision (TME) surgery and stoma. The OPERA trial aims to evaluate whether dose escalation with contact X-ray brachytherapy (CXB) boost improves organ preservation compared to external beam radiotherapy (EBRT) boost. It has been suggested that dose escalation adversely affects surgical outcomes and therefore we report outcomes following TME in OPERA at 36 months. OPERA is a European multicentre phase 3 trial (NCT02505750) which randomises patients with cT2-3a-b, cN0-1, M0 to EBCRT (45 Gy in 25 fractions over 5 weeks with oral capecitabine 825 mg/m2 ) followed by EBRT boost (9 Gy in 5 fractions over 5 days) versus EBCRT followed by CXB boost (90 Gy in 3 fractions over 4 weeks). Patients were assessed at 14, 20 and 24 weeks from the start of treatment. Watch and wait management was adopted for patients who achieved a clinical complete response (cCR) at 24 weeks following treatment. Either local excision (LE) or TME surgery was offered for residual disease or local regrowth, according to patient and surgeon preference. Surgical morbidity and mortality were recorded prospectively. Between July 2015 and June 2020, 148 patients were randomised of which 141 were evaluable in March 2022. At median follow-up of 38.2 months (range: 34.2-42.5), surgery was performed for 66 (47%) patients. A total of 27 (20%) patients had local excision and 39 (29%) had TME surgery, 22/39 (56%) underwent anterior resection and 17/39 (44%) underwent abdominoperineal excision of the rectum. The R0 resection rate was 87%. There were no deaths, and six patients (15%) had Clavien-Dindo IIIb complications. Whilst there was a statistically significant decrease in the TME rate following CXB boost (HR 0.38, 95% CI: 0.19-0.74, p = 0.00419) there was no difference in surgical outcomes between patients who received EBRT and CXB boost. Dose escalation can facilitate nonsurgical treatment for cT2-3 rectal cancer patients who are fit but wish to avoid TME surgery and stoma. If TME surgery is required, then it can be performed safely and effectively.

Sun Myint A ，Rao C ，Barbet N ，Thamphya B ，Pace-Loscos T ，Schiappa R ，Magné N ，Martel-Lafay I ，Mineur L ，Deberne M ，Zilli T ，Dhadda A ，Gerard JP ... -  《-》

Survival analysis of local excision vs total mesorectal excision for middle and low rectal cancer in pT1/pT2 stage and intermediate pathological risk.

Lai IL ，You JF ，Chern YJ ，Tsai WS ，Chiang JM ，Hsieh PS ，Hung HY ，Yeh CY ，Chiang SF ，Lai CC ，Tang RP ，Chen JS ，Hsu YJ ... -  《World Journal of Surgical Oncology》

Dose Escalation Using Contact X-ray Brachytherapy After External Beam Radiotherapy as Nonsurgical Treatment Option for Rectal Cancer: Outcomes From a Single-Center Experience.

To review the outcomes of rectal cancer patients treated with a nonsurgical approach using contact x-ray brachytherapy (CXB) when suspicious residual disease (≤3 cm) was present after external beam chemoradiation therapy/radiation therapy (EBCRT/EBRT). Outcome data for rectal cancer patients referred to our institution from 2003 to 2012 were retrieved from an institutional database. These patients were referred after initial local multidisciplinary team discussion because they were not suitable for, or had refused, surgery. All selected patients received a CXB boost after EBCRT/EBRT. Most patients received a total of 90 Gy of CXB delivered in 3 fractions over 4 weeks. The median follow-up period was 2.5 years (range 1.2-8.3). Of 345 consecutive patients with rectal cancer referred to us, 83 with suspicious residual disease (≤3 cm) after EBCRT/EBRT were identified for a CXB boost. Their median age was 72 years (range 36-87), and 58 (69.9%) were men. The initial tumor stages were cT2 (n = 28) and cT3 (n = 55), and 54.2% were node positive. A clinical complete response (cCR) was achieved in 53 patients (63.8%) after the CXB boost that followed EBCRT/EBRT. Of these 53 patients, 7 (13.2%) developed a relapse after achieving a cCR, and the 6 patients (11.6%) with nonmetastatic regrowth underwent salvage surgery (100%). At the end of the study period, 69 of 83 patients (83.1%) were cancer free. Our data suggest that a CXB boost for selected patients with suspicious residual disease (≤3 cm) after EBCRT/EBRT can be offered as an alternative to radical surgery. In our series, patients with a sustained cCR had a low rate of local regrowth, and those with nonmetastatic regrowth could be salvaged successfully. This approach could provide an alternative treatment option for elderly or comorbid patients who are not suitable for surgery and those with rectal cancer who wish to avoid surgery.

Sun Myint A ，Smith FM ，Gollins S ，Wong H ，Rao C ，Whitmarsh K ，Sripadam R ，Rooney P ，Hershman M ，Pritchard DM ... -  《-》