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Background and Purpose: Despite the excellent clinical outcomes from brachytherapy treatments compared with other modalities and the low associated costs, there have been reports of a decline in utilization of brachytherapy. The aim of this study was to investigate in detail the trend in utilization of brachytherapy in the province of Québec, Canada, from 2011 to 2019., Materials and Methods: All radiotherapy clinics in the province of Quebec, and among these the clinics that provide brachytherapy treatments, were identified. This observational retrospective cohort study involved analysis of data compiled by the Ministère de la Santé et des Services Sociaux du Québec for the period of 2011 to end of 2019 on all brachytherapy procedures performed in the province of Quebec. Time series graphs were used to describe the number of high dose rate (HDR) and low dose rate (LDR) brachytherapy treatments during the studied time period. Statistical analysis was conducted using R statistical software., Results: Between 2011 and 2019, 12 hospitals in the province of Québec provided radiotherapy treatments, and all of them offered brachytherapy services. The median annual number of brachytherapy sessions was 4413 (range 3930-4829). HDR brachytherapy represented over 90% of all brachytherapy treatments throughout the study period. Significant changes over time were observed in the number of treatments: at least 5% change was seen only for the two most common subtypes of brachytherapy, HDR interstitial and HDR intracavitary, with an increase of 9.6% and a decrease of 9.2%, respectively. The use of other subtypes of brachytherapy (HDR-plesiotherapy, LDR-interstitial, LDR-intracavitary, LDR-eye plaque) was stable between 2011 and 2019, with ≤ 2.5% variation., Conclusion: This study demonstrates an overall steady use of brachytherapy between 2011 and 2019 in Quebec. Brachytherapy offers numerous advantages for the treatment of diverse cancer sites. Although more sophisticated external beam radiotherapy treatments have emerged in the last decades, the precision and cost-effectiveness of brachytherapy remain unbeaten. To ensure the continued use and availability of brachytherapy, governments must put in place policies and regulations to that effect. Training and exposure of future health care professionals to brachytherapy within Quebec and Canada is essential to provide all patients the same access to this life saving modality., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: We describe methods to improve dose delivery for patients with rectal cancer receiving boost brachytherapy after external beam radiotherapy., Methods and Materials: Patients with rectal cancer who were ineligible or refusing surgery are treated with external beam radiotherapy and subsequently with three weekly image-guided volume-adapted high-dose-rate brachytherapy boosts of 10 Gy to the residual clinical target volume, for a total of 30 Gy in three fractions. Tungsten shielding placed at the center of intracavitary mold applicator and double-balloon technique was used to improve dose conformity to the target., Results: Our results show that the use of tungsten shield and double balloon reduces the dose gradient within the target volume to receive the prescription boost dose of 10 Gy from maximum dose of 60 Gy down to 20 Gy., Conclusions: We outlined two methods for achieving higher high-dose-rate brachytherapy dose conformity using the tungsten shielding rods (to spare contralateral healthy tissues) and double-balloon technique (to decrease dose gradient within the target to minimize dose to the proximal mucosa)., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Endorectal brachytherapy is an attractive option in the neoadjuvant setting for locally advanced rectal cancer, but it is not considered standard of care., Objective: This study aimed to compare pathologic outcomes of patients with clinical T3 rectal cancer who underwent high-dose-rate endorectal brachytherapy with those who underwent conventional external beam radiotherapy., Design: This study is a retrospective chart review., Settings: This study was conducted in a single large tertiary academic colorectal surgery practice in Canada., Patients: Adult patients with MRI-staged T3 rectal adenocarcinoma treated with neoadjuvant radiotherapy followed by total mesorectal excision from 2007 to 2016 were included., Interventions: Neoadjuvant radiotherapy was delivered by high-dose-rate endorectal brachytherapy or conventional external beam radiotherapy., Main Outcome Measures: Primary outcome was pathologic complete response, defined as ypT0N0. Secondary outcomes included tumor (T stage) and lymph node (N stage) downstaging and tumor regression grade., Results: Ninety-nine patients were identified as having clinical T3 rectal cancer based on blinded pretreatment MRI review. Mean age was 66.2 years (± 6.2) and 59 patients (59.6%) were male. Thirty-three patients were clinically node negative (33.3%), 45 had c-N1 disease (45.5%), and 21 had c-N2 disease (21.2%). Sixty-four patients (64.6%) underwent high-dose-rate endorectal brachytherapy and 35 (35.4%) underwent external beam radiotherapy. The high-dose-rate endorectal brachytherapy group had a lower median mesorectal depth of invasion (4 mm vs 5 mm, p = 0.010); all other preoperative tumor characteristics were similar in both groups. Eighteen patients (18.2%) achieved pathologic complete response: 12 in the high-dose-rate endorectal brachytherapy group and 6 in the conventional external beam radiotherapy group (18.8% vs 17.1%, p = 0.84). High-dose-rate endorectal brachytherapy was superior to conventional radiotherapy for tumor (T stage) downstaging (59.4% vs 28.6%, p = 0.0030) but not for lymph node (N stage) downstaging (35.9% vs 51.4%, p = 0.14)., Limitations: This study was limited by its retrospective nature and modest sample size., Conclusions: Neoadjuvant treatment of T3 rectal cancer with high-dose-rate endorectal brachytherapy appears to achieve equivalent rates of pathologic complete response and superior T-stage downstaging compared with conventional external beam radiotherapy. See Video Abstract at http://links.lww.com/DCR/A905.

Purpose: The Papillon technique using 50-kVp soft X-rays to treat rectal adenocarcinomas was developed and clinically implemented in the 1960s. We describe differences between accurate dosimetry and clinical implementation of this technique that is extending from its very inception to date., Methods and Materials: A renaissance of the Papillon technique occurred with two recently introduced 50-kVp systems: Papillon+ by Ariane and a custom-made rectal applicator (consisting of a surface applicator inserted into a proctoscope) by iCAD's Xoft Axxent Electronic Brachytherapy (eBT) System (iCad, Inc., Sunnyvale, CA). In contrast to the initial design, we investigated the impact of introducing a plastic lid, which would provide more reproducible and more accurate dose delivery across the rectal adenocarcinoma patient population. We use both parallel-plate chamber and radiochromic film dosimeters to determine differences in basic dosimetry characteristics (beam half-value layers, outputs, percent depth doses, and profiles) between the Xoft Electronic Brachytherapy rectal applicator system with and without the plastic lid in place., Results: Compared to the open-cone applicator, the proposed applicator with the plastic lid produces a slightly harder (more penetrating) beam quality (half-value layer of 1.4 vs. 1.3-mm Al), but with reduced output (by 33%), and a slightly broader beam with flatness not worse than 3% and symmetry not worse than 2%., Conclusions: In addition to characterizing beam properties modified by the possible introduction of the plastic cap, we also pointed out and addressed misconceptions in the use of radiochromic films for dose measurements at low-energy photon beams., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this work was to design a novel high-dose rate (HDR) ((192)Ir) brachytherapy applicator for treatment of rectal carcinomas that uses tungsten shielding for possibly improved dosimetric results over commercial brachytherapy applicator(s)., Methods: A set of 15 single-depth applicators and one dual-depth applicator were designed and simulated using Monte Carlo (MCNPX). All applicators simulated were high-density tungsten alloy cylinders, 16-mm in diameter, and 60-mm long, with longitudinal grooves within which an (192)Ir source can be placed. The single-depth designs varied regarding the number and depth of these grooves, ranging from 8 to 16 and 1-mm to 3-mm, respectively. The dual-depth design had ten channels, each of which had two depths at which the source could be placed. Optimized treatment plans were generated for each design on data from 13 treated patients (36 fractions) with asymmetrical clinical target volumes (CTVs). All results were compared against the clinically treated plans which used intracavitary mold applicator (ICMA), as well as a recently designed, highly automated, and collimated intensity modulation device named dynamic modulated brachytherapy (DMBT) device., Results: All applicator designs outperformed the ICMA in every calculated dosimetric criteria, except the total dwell times (∼30% increase). There were clear, but relative, tradeoffs regarding both the number of channels and the depth of each channel. Overall, the 12-channel, 1-mm depth, and 14-channel 2-mm depth designs had the best results of the simpler designs, sparing the healthy rectal tissues the most while achieving comparable CTV coverage with the dose heterogeneity index and lateral spill doses improving by over 10% and the contralateral healthy rectum dose dropping over 30% compared to ICMA. The ten-channel dual-depth design outperformed each single-depth design, yielding the best coverage and sparing., Conclusions: New grooved tungsten HDR-brachytherapy devices have been designed and simulated. The results of this work attest to the capability of these new, highly anisotropic, intelligently shielded applicators to limit dose to healthy tissues while maintaining a conformal prescription dose to the CTV.

Purpose: All forms of past and current high-dose-rate brachytherapy utilize immobile applicators during treatment delivery. The only moving part is the source itself. This paradigm misses an important degree of freedom that, if explored, can in some instances produce previously unachievable dose conformality; that is, the dynamic motion of the applicator itself during treatment delivery. Monte Carlo and treatment planning simulations were used to illustrate the potential benefits of moving applicators for rectal cancer applications in particular. This concept is termed dynamic modulated brachytherapy (DMBT)., Methods: The DMBT system uses a high-density, 18.0 g∕cm(3), 45 mm long tungsten alloy shield, cylindrical in shape, with a small window on one side to encapsulate a (192)Ir source, to create collimation that results in a highly directional beam profile. This shield can be dynamically translated and rotated, using an attached robotic arm, during treatment to create a volumetric modulated arc therapy-type delivery, but from inside the rectal cavity. Monte Carlo simulations and planning optimization algorithms were developed inhouse to evaluate the effectiveness of this new approach using 36 clinical treatment plans comprised of 13 patients each treated using the intracavitary mold applicator (ICMA, Nucletron, The Netherlands) to quantify the potential clinical benefit. The prescription dose was 10 Gy∕fx and the group had an average clinical target volume of 9.0 ± 3.5 cm(3). Ideal phantom geometries were used to evaluate the impact of various shield dimensions and designs on the resulting plan quality., Results: Simulations of ideal phantom geometries found that shields as small as 10 mm in diameter can produce high quality plans. For the clinical patient cases, compared to the ICMA, for equal prescription tumor coverage, the DMBT plans provided >30% decrease in D(5) (high dose volume) resulting in a ∼40% decrease in dose heterogeneity index. In addition, mean dose and D(98) showed a reduction (typically 40%-60%) on all critical structures evaluated. However, for a 10 Gy prescribed dose there was an increase in total treatment time on average from 7.6 to 20.8 min for a source with an air-kerma strength of 40.25 kU (10 Ci)., Conclusions: Dosimetric properties of a novel DMBT system have been described and evaluated. Comparison with the ICMA commercial applicator has shown it to be a prospective step forward in high-dose-rate brachytherapy (192)Ir technology. Dynamic motion of an applicator during treatment, for any applicator and site in general, can provide additional degrees of freedom that, if properly considered, can potentially increase the plan quality significantly.

Purpose: Acute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT)., Methods and Materials: Fifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receive the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT., Results: At the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078)., Conclusions: This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Colorectal cancer patients are treated at our hospital with 192Ir high dose rate (HDR) brachytherapy using an applicator that allows the introduction of a lead or tungsten shielding rod to reduce the dose to healthy tissue. The clinical dose planning calculations are, however, currently performed without taking the shielding into account. To study the dose distributions in shielded cases, three techniques were employed. The first technique was to adapt a shielding algorithm which is part of the Nucletron PLATO HDR treatment planning system. The isodose pattern exhibited unexpected features but was found to be a reasonable approximation. The second technique employed a ray tracing algorithm that assigns a constant dose ratio with/without shielding behind the shielding along a radial line originating from the source. The dose calculation results were similar to the results from the first technique but with improved accuracy. The third and most accurate technique used a dose-matrix-superposition algorithm, based on Monte Carlo calculations. The results from the latter technique showed quantitatively that the dose to healthy tissue is reduced significantly in the presence of shielding. However, it was also found that the dose to the tumor may be affected by the presence of shielding; for about a quarter of the patients treated the volume covered by the 100% isodose lines was reduced by more than 5%, leading to potential tumor cold spots. Use of any of the three shielding algorithms results in improved dose estimates to healthy tissue and the tumor.

Background: The objective of this study was to assess the value of apoptosis protease-activating factor 1 (APAF-1) as a predictive marker of response in rectal tumors treated with preoperative, high-dose-rate endorectal brachytherapy., Methods: Immunohistochemistry for APAF-1 was performed on 94 rectal tumor biopsy specimens from patients who were treated on a preoperative, high-dose-rate brachytherapy protocol. Tumors were considered positive when > 10% of tumor cells were immunoreactive. The association between APAF-1 expression and tumor response was made using the chi-square test., Results: Forty-four tumors (43%) were positive for APAF-1. Thirty tumors had complete pathologic tumor regression after preoperative radiotherapy. Of these, 18 tumors were positive for APAF-1. A partial response occurred in 35 tumors. Eighteen tumors (51%) were positive for the protein. Only 8 of 29 nonresponsive tumors (28%) were immunoreactive for APAF-1. A significant association was found between complete tumor regression and positive APAF-1 status (P = 0.018). APAF-1 expression in partially responsive tumors was significantly greater than in nonresponsive tumors (P = 0.03)., Conclusions: APAF-1 expression in pretreatment rectal tumor biopsy specimens may be useful as a predictive marker of response to preoperative radiotherapy in patients with rectal carcinoma.

Simple Summary: This prospective phase II–III randomized trial explores the value of modern technology for prudent radiation dose escalation in the curative management of patients with rectal cancer. It includes 40 operable patients with locally advanced operable rectal cancer. This manuscript illustrates the planned interim analysis, which was intended to confirm safety, including the absence of unexpected toxicities and the inability to perform salvage surgery. The treatment approach involves pelvic chemoradiotherapy followed by either an additional external beam radiation boost or three weekly boosts of brachytherapy, which are adapted in real-time to tumor response. This proof-of-principle study shows that careful radiotherapy dose escalation leads to high proportions of sustained complete clinical response in patients with rectal cancer with acceptable toxicity. Ongoing accrual to the phase III component of the trial is in progress. Background: We explored image-guided adaptive endorectal brachytherapy patients electing non-operative management for rectal cancer. We present the first pre-planned interim analysis. Methods: In this open-label phase II–III randomized study, patients with operable cT2-3ab N0 M0 rectal cancer received 45 Gy in 25 fractions of pelvic external beam radiotherapy (EBRT) with 5-FU/Capecitabine. They were randomized 1:1 to receive either an EBRT boost of 9 Gy in 5 fractions (Arm A) or three weekly adaptive brachytherapy (IGAEBT) boosts totaling 30 Gy (Arm B). Patient characteristics and toxicity are presented using descriptive analyses; TME-free survival between arms with the intention to treat the population is explored using the Kaplan–Meier method. Results: A total of 40 patients were in this analysis. Baseline characteristics were balanced; acute toxicities were similar. Complete clinical response (cCR) was 50% (n = 10/20) in Arm A and 90% in Arm B (n = 18/20). Median follow-up was 1.3 years; 2-year TME-free survival was 38.6% (95% CI: 16.5–60.6%) in the EBRT arm and 76.6% (95% CI: 56.1–97.1%) in the IGAEBT arm. Conclusions: Radiation intensification with IGAEBT is feasible. This interim analysis suggests an improvement in TME-free survival when comparing IGAEBT with EBRT, pending confirmation upon completion of this trial. [ABSTRACT FROM AUTHOR]

Simple Summary: Organ preservation is becoming a topic of great interest for rectal cancer. Radiotherapy, often in association with chemotherapy, is playing a major role in achieving tumor sterilization and long-term local control. In order to achieve this goal, a high dose (>70 Gy) of radiotherapy is necessary. To avoid radiation toxicity of such a high dose, an endocavitary approach using contact X-ray 50 kV brachytherapy (CXB) is an attractive method. Historical series and two randomized trials in Europe give good evidence of the merit of CXB. The selection of early tumors is a key prognostic factor to achieve good results. A planned organ preservation treatment using CXB followed by chemoradiotherapy can be proposed to patients with T2–T3 a–b < 3 cm in diameter. At 3 years, the chance of local control should be close to 90% with good bowel function. 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. [ABSTRACT FROM AUTHOR]