Image-guided high-dose-rate brachytherapy for rectal cancer: technical note and first clinical experience on an organ-preserving approach

Strahlenther Onkol https://doi.org/10.1007/s00066-022-01931-4 ORIGINAL ARTICLE Image-guided high-dose-rate brachytherapy for rectal cancer: technical note and first clinical experience on an organ-preserving approach Maximilian Fleischmann1 · Markus Diefenhardt1 · Martin Trommel1 · Christian Scherf1 · Ulla Ramm1 · Georgios Chatzikonstantinou1 · Emmanouil Fokas1,2,3,4 · Claus Rödel1,2,3,4 · Nikolaos Tselis1 Received: 3 January 2022 / Accepted: 10 March 2022 © The Author(s) 2022 Abstract Purpose As the population ages, the incidence of rectal cancer among elderly patients is rising. Due to the risk of perioperative morbidity and mortality, alternative nonoperative treatment options have been explored in elderly and frail patients who are clinically inoperable or refuse surgery. Methods Here we present technical considerations and first clinical experience after treating a cohort of six rectal cancer patients (T1-3, N0-1, M0; UICC stage I-IIIB) with definitive external-beam radiation therapy (EBRT) followed by image-guided, endorectal high-dose-rate brachytherapy (HDR-BT). Patients were treated with 10–13 × 3 Gy EBRT followed by HDR-BT delivering 12–18 Gy in two or three fractions. Tumor response was evaluated using endoscopy and magnetic resonance imaging of the pelvis. Results Median age was 84 years. All patients completed EBRT and HDR-BT without any high-grade toxicity (> grade 2). One patient experienced rectal bleeding (grade 2) after 10 weeks. Four patients (67%) demonstrated clinical complete response (cCR) or near cCR, there was one partial response, and one residual tumor and hepatic metastasis 8 weeks after HDR-BT. The median follow-up time for all six patients is 42 weeks (range 8–60 weeks). Sustained cCR without evidence of local regrowth has been achieved in all four patients with initial (n)cCR to date. Conclusion Primary EBRT combined with HDR-BT is feasible and well tolerated with promising response rates in elderly and frail rectal cancer patients. The concept could be an integral part of a highly individualized and selective nonoperative treatment offered to patients who are not suitable for or refuse surgery. Keywords Rectal cancer · Radiotherapy · Brachytherapy · Endoluminal · Endorectal · Nonoperative management · Organ preservation · Complete response Introduction Availability of data and material The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.  Maximilian Fleischmann 1 Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany 2 German Cancer Research Center (DKFZ), Heidelberg, Germany 3 Partner Site Frankfurt am Main, German Cancer Consortium (DKTK), Frankfurt, Germany 4 Frankfurt Cancer Institute, Frankfurt, Germany Multimodal treatment strategies have enabled selective organ preservation and resulted in a paradigm shift in the management of rectal cancer. In patients with locally advanced rectal cancer, total neoadjuvant therapy (TNT) has significantly improved pathological complete response (pCR) and disease-free survival (DFS) rates, as recently demonstrated by the phase III randomized RAPIDO and PRODIGE-23 trials [1–3]. Given the morbidity of radical surgery, such as temporary/permanent colostomy, stool incontinence, and urinary and sexual dysfunction, a selective nonoperative management (NOM) approach offers an opportunity to avoid a negative and profound long-term impact on quality of life in patients with clinical complete K Strahlenther Onkol response [4–6]. However, TNT concepts currently being investigated to improve functional outcomes and quality of life incorporate intensified chemotherapy regimens and are often not feasible in elderly and frail patients due to multiple comorbidities. Moreover, major surgery poses a high risk of perioperative complications and mortality in these patients [7–10]. Radiation therapy (RT) dose escalation is associated with increased tumor regression and improved response rates in rectal cancer. However, dose response analyses indicate that a biologically equivalent dose (EQD2) of 92 Gy is required to achieve pCR in approximately 50% of patients with locally advanced disease by RT alone [11, 12]. Emerging NOM and/or local excision (LE) approaches after RT alone have been reported for localized and early-stage disease [13, 14]. In this context, contact x-ray brachytherapy (CXB), usually performed with 50-kV x-rays, has shown local control rates up to 86% for selected T2-3 tumors less than 3 cm in diameter [15–19]. Alternatively, endorectal high-doserate brachytherapy (HDR-BT) delivers a highly conformal dose distribution with steep dose gradients, also covering higher volumes and locally advanced tumors. Previous data on definitive RT consisting of external-beam radiation therapy (EBRT) followed by an endorectal HDR-BT boost have demonstrated promising local control rates and tolerable toxicity rates [20–25]. We here report our first experience on definitive RT combining EBRT and image-guided endorectal HDR-BT in a cohort of six elderly and frail rectal cancer patients not suitable for or refusing radical surgery. Materials and methods Treatment The treatment regimen consisted of EBRT followed by a restaging assessment (RA) and sequential image-guided endorectal HDR-BT. EBRT was applied as intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) and, if feasible, in prone position using a belly board. Patients received 30 to 39 Gy in 10 or 13 daily fractions, respectively. Initially, a dose of 30 Gy in 10 fractions was prescribed to evaluate tolerability in this vulnerable patient cohort. After 10 × 3 Gy proved to be not associated with increased toxicity and did not affect the feasibility of this combined approach (EBRT + HDR-BT), we increased the EBRT dose to 13 × 3 Gy. Clinical target volumes (CTV) included the primary tumor with margins, the involved lymph nodes, as well as the mesorectum, presacral, and internal iliac lymph nodes up to S2-3 in low rectal tumors without suspected lymph node involvement, or the interspace, or L5-S1, respectively. The inferior border was at least 3 cm below the primary tumor. Bladder, small K intestines, and the femoral head were defined as organs at risk (OAR). Six weeks after EBRT and prior to the first HDR-BT, MRI of the pelvis and endoscopy were performed to evaluate treatment response and the residual extent of disease for target outlining. Patients were prepared for treatment with a whole-bowel irrigation to ensure clean intestines. During endoscopy, radiopaque CT markers were placed at the lateral, proximal, and distal margin of the residual tumor for target volume delineation and image guidance during treatment. A cylindrical intracavitary mold applicator (Elekta AB, Sweden) with eight radially shaped treatment catheters of 270 mm in length (...truncated)