Technique adaptation, strategic replanning, and team ... - Brachytherapy

Brachytherapy 17 (2018) 86e93

Treatment Delivery Verification in Brachytherapy

Technique adaptation, strategic replanning, and team learning during implementation of MR-guided brachytherapy for cervical cancer Julia Skliarenko1,2, Marco Carlone1,2, Kari Tanderup3, Kathy Han1,2, Akbar Beiki-Ardakani1, Jette Borg1,2, Kitty Chan1,2, Jennifer Croke1,2, Alexandra Rink1,2, Anna Simeonov1,2, Reem Ujaimi1,2, Jason Xie1, Anthony Fyles1,2, Michael Milosevic1,2,* 1

Radiation Medicine Program, University Health Network and Princess Margaret Cancer Centre, Toronto, Canada 2 Department of Radiation Oncology, University of Toronto, Toronto, Canada 3 Department of Oncology, Aarhus University Hospital, Aarhus, Denmark

ABSTRACT

PURPOSE: MR-guided brachytherapy (MRgBT) with interstitial needles is associated with improved outcomes in cervical cancer patients. However, there are implementation barriers, including magnetic resonance (MR) access, practitioner familiarity/comfort, and efficiency. This study explores a graded MRgBT implementation strategy that included the adaptive use of needles, strategic use of MR imaging/planning, and team learning. METHODS AND MATERIALS: Twenty patients with cervical cancer were treated with highdose-rate MRgBT (28 Gy in four fractions, two insertions, daily MR imaging/planning). A tandem/ring applicator alone was used for the first insertion in most patients. Needles were added for the second insertion based on evaluation of the initial dosimetry. An interdisciplinary expert team reviewed and discussed the MR images and treatment plans. RESULTS: Dosimetry-trigger technique adaptation with the addition of needles for the second insertion improved target coverage in all patients with suboptimal dosimetry initially without compromising organ-at-risk (OAR) sparing. Target and OAR planning objectives were achieved in most patients. There were small or no systematic differences in tumor or OAR dosimetry between imaging/planning once per insertion vs. daily and only small random variations. Peer review and discussion of images, contours, and plans promoted learning and process development. CONCLUSIONS: Technique adaptation based on the initial dosimetry is an efficient approach to implementing MRgBT while gaining comfort with the use of needles. MR imaging and planning once per insertion is safe in most patients as long as applicator shifts, and large anatomical changes are excluded. Team learning is essential to building individual and programmatic competencies. Ó 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Keywords:

Cervical cancer; Magnetic resonance imaging; Radiotherapy; Interstitial brachytherapy; Adaptive planning

Introduction Despite the availability of screening and, more recently, human papillomavirus vaccination programs, cervical cancer remains a major global health problem (1). A significant proportion of patients with cervical cancer present with locally advanced and/or node positive disease, which Received 4 February 2017; received in revised form 17 November 2017; accepted 20 November 2017. Financial disclosure: The Giovanni and Concetta Guglietti Family Cancer Fund supported this work. * Corresponding author. University Health Network and Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9. Tel.: þ1-416-946-2932; fax: þ1-416-946-2227. E-mail address: [email protected] (M. Milosevic).

cannot be cured surgically. The standard of care for these patients is external beam radiotherapy (EBRT) and concurrent weekly cisplatin followed by brachytherapy. Historically, 50e60% of advanced stage cervical cancer patients were cured with this approach (2). Population-based studies have demonstrated that brachytherapy is an essential element of radiation therapy for cervical cancer resulting in improved cause-specific survival and overall survival rates (3). Traditionally, brachytherapy has been delivered using an intracavitary applicator and two-dimensional (2D) treatment planning with orthogonal radiographs and point-based dose prescriptions. This approach, however, offers little flexibility in tailoring treatment plans to each patient’s unique tumor

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J. Skliarenko et al. / Brachytherapy 17 (2018) 86e93

and normal organ characteristics. Parameters such as tumor size, extent of local invasion, and location of organs at risk (OARs) are not taken into account with this approach. As a result, patients receiving 2D brachytherapy are at risk of having less optimal clinical outcomes from incomplete tumor coverage and also higher treatment complications from excess doses delivered to OARs. Magnetic resonance (MR) imaging is known to provide superior soft tissue resolution within the pelvis, thereby facilitating identification of cervical tumor extent and delineation of normal organs (4e7). MR guidance facilitates more complex treatment geometries with both intracavitary and interstitial needles and three-dimensional volumetric treatment planning with dynamic plan adaptation to compensate for tumor and OAR changes over time. MR-guided brachytherapy (MRgBT) has been shown to enable safe tumor dose escalation while simultaneously limiting normal tissue doses, thereby expanding the therapeutic ratio (8, 9). Several single- and multi-institutional clinical studies have suggested improved local control with MRgBT in patients with cervical cancer compared to historical 2D treatment approaches (10e17). The most promising results have come from institutions that used interstitial needles in a high proportion of patients to improve tumor coverage, OAR sparing, or both (12, 14). While the clinical benefits of MRI-guided cervical brachytherapy with interstitial needles when necessary have been demonstrated, translation of this approach to routine practice is lagging in North America. Although it is believed that MRgBT will be the standard of care within 5 years (18), many centers in Canada and the United States with active cervical cancer brachytherapy programs continue to use traditional 2D treatment techniques (19, 20). MRgBT is considerably more demanding of resources, and optimized, efficient, and safe processes are of paramount importance in assuring widespread availability. Barriers to implementation include the availability of MR for each brachytherapy fraction, practitioner familiarity, and comfort with the technique, including the use of interstitial needles, contouring and treatment planning, and the added time necessary for treatment (18). Our program transitioned from pulse-dose-rate brachytherapy to high-dose-rate (HDR) MRgBT with interstitial needles in 2014. This study follows the learning trajectory from a simple MR-guided pulse-dose-rate technique to a more complex HDR technique with a tandem/ring applicator plus needles and two insertions per patient. The specific aims were to: (1) explore the feasibility of a dosimetry-triggered technique adaptation strategy to gain comfort with the use of interstitial needles and better understand the benefits and risks; a standard tandem/ring applicator alone was used for the first insertion with the addition of needles for the second insertion if needed based on the Fraction 1 predicted target coverage, (2) determine the need for MR imaging and planning prior to each brachytherapy fraction compared to a less intensive

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approach with imaging and planning once per insertion, as a means of reducing resource demands and improving efficiency, and (3) evaluate the importance of team learning as a driver of process change.

Methods and materials Patient characteristics Twenty patients with biopsy-proven International Federation of Gynecology and Obstetrics stage IB-IIIB carcinoma of the cervix undergoing radical radiotherapy and concurrent cisplatin chemotherapy were accrued to this study in 2014 during a period of programmatic transition and rapid learning about MRgBT. The median age was 49 years (range, 27e72). Most patients had squamous cell carcinoma (n 5 15), with the remaining having adenocarcinoma (n 5 2), adenosquamous carcinoma (n 5 2), or carcinosarcoma (n 5 1). The characteristics of these patients are summarized in Table 1. The hospital ethics review board approved the study. Treatment of cervical cancer All patients received EBRT and concurrent cisplatin chemotherapy followed by MRgBT. Pelvic EBRT was delivered using a conformal four-field technique and 18 MV photons to a prescribed dose of 45e50.4 Gy in 1.8e2 Gy daily fractions. Cisplatin 40 mg/m2 was administered weekly during external beam treatment.

Table 1 Patient and tumor characteristics Characteristic Eligible patients Age (years) Histology Squamous cell carcinoma Adenocarcinoma Adenosquamous carcinoma Carcinosarcoma FIGO stage IB/IIA IIB IIIB/IVA Max primary tumor size at diagnosis (cm) Primary tumor volume at BT (cm3) Pelvic lymphadenopathy Yes No External beam dose 45 Gy in 25 fractions 50 Gy in 25 fractions 50.4 Gy in 28 fractions

Median

Range

49

27e72

Total (%) 20

15 2 2 1

(75) (10) (10) (5)

11 (55) 8 (40) 1 (5) 4.6 42

2.1e9.5 19e94

11 (55) 9 (45) 8 (40) 4 (20) 8 (40)

BT 5 brachytherapy; FIGO 5 International Federation of Gynecology and Obstetrics.

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MR-guided HDR brachytherapy was initiated usually within 1 week of completing EBRT using an MRcompatible tandem/ring applicator with or without blunt, plastic interstitial needles (Elekta Canada). Two applicator insertions were performed under general anesthesia approximately 1 week apart. Two 7 Gy HDR fractions were delivered per insertion separated by 18e24 h; patients remained in hospital between fractions with the applicator and a urinary catheter in situ. The total prescribed brachytherapy dose was 28 Gy in four fractions. The use of interstitial needles evolved during the study as the treatment team became more familiar with the indications and dosimetric advantages. In the early phases, an intracavitary applicator alone was used for the first insertion. The treatment technique was then adapted at the second insertion to include needles if necessary to achieve optimal target coverage and/or OAR sparing. By the end of the study, needles were also being used for the first insertion if prebrachytherapy MR imaging suggested a benefit. MR imaging and brachytherapy planning with the intracavitary applicator and needles (if used) in situ were performed four times, once immediately prior to each fraction. Axial, fast spin echo T2-weighted MR images were obtained using a 3 T dedicated MR simulator (Siemens, Verio) from approximately the midsacrum to the bottom of the ischial tuberosities (TE/TR 102/4500 ms, slice/gap thickness 3/0 mm, matrix 320 256, FOV 20 cm). Three-dimensional SPACE (TE/TR 133/1500 ms, slice/gap thickness 8/0 mm, matrix 320 256, FOV 24 cm) and VIBE (TE/TR 2.38/5.03 ms, slice/gap thickness 1.5/0 mm, matrix 320 256, FOV 24 cm) sequences were also acquired, the latter to facilitate needle localization and reconstruction. An 8-channel phased array torso coil was used for all scans. Targets and OARs were contoured as per the EMBRACE study protocol (21) and named using the International Commission of Radiation Units and Measures Report No. 89 revised terminology (22). The residual gross tumor volume at brachytherapy was defined by high T2 signal. The high-risk clinical target volume (CTV) (CTVHR) was taken to be the union of the residual gross tumor volume with the whole cervix and any parametrial ‘‘gray zones.’’ The bladder, rectum, and sigmoid were contoured as hollow organs. Optimized treatment planning prior to each brachytherapy fraction was done using the Oncentra planning system (Elekta Canada) in an adaptive, iterative manner incorporating all available anatomical and dosimetric information to that point in time. It was assumed that the CTVHR and relevant bladder and rectal volumes received the full, prescribed EBRT dose. The following planning objectives were used (21, 22): minimum combined EBRT and brachytherapy biological effective dose normalized to 2 Gy fractions using an a/b of 10 (equivalent 2 Gy dose, EQD210) of 85 Gye90% of the CTVHR (CTVHR D90%); and combined biological effective doses normalized to 2 Gy fractions using an a/b of 3 (EQD23) to the maximally irradiated (not necessary contiguous) 2 cm3 volumes (D2cm3) of bladder, rectum, and sigmoid of 90, 75, and 75 Gy, respectively. In general,

the CTVHR D90% was maximized consistent with the constraints imposed by the OAR D2cm3 planning objectives, at the discretion of the responsible radiation oncologist. All images, contours, and treatment plans were reviewed by an interdisciplinary team of experts in gynecologic radiation oncology during routine peer-review rounds, a provincewide initiative to improve quality of care among patients undergoing radiation treatment (23). Analysis For the 20 patients in this study, there were 40 applicator insertions, 80 planning MRs, 80 contoured data sets, and 80 HDR treatment plans. To evaluate the impact of treatment adaptation and daily planning on overall tumor and OAR dosimetry, 5 MR imaging/planning scenarios were considered: 1. F1 projected: Fraction 1 plan projected over the course of treatment, assuming the same Day 1 target and OAR anatomy throughout. The Fraction 1 CTVHR D90% and OAR D2cm3 doses were multiplied by a factor of four to calculate projected doses over the entire course of treatment. 2. F1 anatomically corrected: Fraction 1 plan applied to the Day 2, 3, and 4 target and OAR anatomy without plan reoptimization. 3. F1þF3 imaging/planning: Fraction 1 plan projected to Fraction 2 and Fraction 3 plan projected to Fraction 4, assuming the same target and OAR anatomy on Days 1 and 2 and on Days 3 and 4. This reflects MR imaging and planning once for reach insertion. 4. F1þF3 anatomically corrected: Fraction 1 plan applied to the Day 2 anatomy without replanning, and the Fraction 3 plan applied to the Day 4 target and OAR anatomy without plan reoptimization on Days 2 and 4. 5. F1-4 optimal: MR imaging and adaptive replanning prior to each brachytherapy fraction, incorporating daily changes in target and OAR anatomy. This ‘‘gold standard’’ approach, while demanding of resources, accounts for all prior and present anatomical and dosimetric information at each planning time point. The patients in this study were treated in this manner. CTVHR D90% and OAR D2cm3 values were expressed as means SDs, rounded to two significant digits. Dosimetric correlations between two imaging/planning scenarios were evaluated using Pearson’s correlation coefficient. Systematic and random differences between two imaging/planning scenarios were evaluated using the paired samples t test and expressed as means SDs.

Results A tandem/ring applicator alone was used for the first insertion in 17 patients (85%). A tandem/ring applicator with interstitial needles was used in 3 patients (15%)


toward the end of the yearlong study as the interdisciplinary team of oncologists, physicists, and radiation therapists became more comfortable with the technique. As shown in Table 2, the mean CTVHR and OAR doses were similar among the 5 MR imaging/planning scenarios. The CTVHR D90% planning objective of 85 Gy was achieved in 60%, 60%, 90%, 85%, and 90% of patients with the F1 projected, F1 anatomically corrected, F1þF3 projected, F1þF3 anatomically corrected, and F1-4 optimal imaging/planning scenarios, respectively. The dosimetric reporting uncertainty for the F1 projected and F1þ3 projected scenarios due to changes in applicator geometry and/or target and OAR anatomy from fraction to fraction are also shown in Table 2. The systematic and random CTVHR D90% and OAR D2cm3 uncertainties were represented by the means and SDs, respectively, of the patient-specific dose differences between the anatomically corrected and projected scenarios. The CTVHR D90% systematic reporting uncertainty was !2% of the CTVHR D90% 85 Gy planning objective for both the F1 projected and F1þF3 projected strategies. The OAR D2cm3 systematic uncertainties were similarly small and generally !1.5% of the planning objectives. There was a trend toward higher random uncertainty with the F1 strategy than with the F1þF3 strategy. There were differences of O5% of the 85 Gy planning objective between the anatomically corrected CTVHR D90% and projected CTVHR D90% in 6 patients with the F1 strategy but in none of the patients with the F1þF3 strategy. The results were similar for the OARs, with rectal D2cm3 differences O5% in 8 vs. 1 patient(s), sigmoid D2cm3 differencesO5% in 6 vs. 3 patients, and bladder D2cm3 differencesO5% in 4 vs. 1 patient(s). With the F1þF3 strategy, the CTVHR D90% random uncertainty was !2.5% of the planning objective and the rectum, sigmoid, and bladder D2cm3 random uncertainties were !6.5%, !4.5%, and !3% of the planning objectives, respectively. F1 dosimetry-triggered treatment technique adaptation The need for interstitial needles to optimize target coverage and OAR sparing can be difficult to anticipate based on MR imaging prior to applicator insertion, particularly for those inexperienced with the technique. The first

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objective of the study was to determine the feasibility of using a simple ring/tandem applicator that is familiar to most radiation oncologists, physicists, and therapists who treat cervical cancer for the first insertion, with the introduction of needles for the second insertion if needed based on the projected F1 CTVHR D90% over the entire course of treatment and preplanning using the F1 geometry. The mean F1 projected CTVHR D90% was 87 9.3 Gy. In 8 patients, the F1 projected CTVHR D90% was between 0.8 and 13.5 Gy below the planning objective of 85 Gy, as shown in Fig. 1. The treatment plan geometry was adapted at the second insertion in 7 of the 8 patients with suboptimal F1 projected CTVHR D90% and in three others where interdisciplinary peer review identified opportunities for improved OAR sparing. Interstitial needles were added in eight cases where a tandem/ring applicator alone was used for the first insertion. Additional needles were added in two cases where the requirement for needles was anticipated prior to the first insertion. In 1 patient (arrow in Fig. 1), peer review on Day 1 identified ways to improve the plan without adapting the treatment geometry. Comparing the F1 projected CTVHR D90% (preadaptation) to the F3 projected CTVHR D90% (postadaptation) within individual patients (Fig. 1), there was a 16.3 5.8 Gy ( p ! 0.0001, paired t test) increase in the 10 who underwent plan adaptation and, as expected, no difference (2.0 6.6 Gy) in the 10 without adaptation. The F1þF3 projected CTVHR D90% was intermediate between the F1 projected and F3 projected doses, with an 8.3 3.7 Gy ( p ! 0.0001) increase relative to the F1 projected CTVHR D90% in patients who underwent adaptation (data not shown). This difference (mean improvement of 16.3 Gy with needles for four fractions vs. 8.3 Gy with needles for only the last two fractions) provides an indication of the ‘‘dosimetric cost’’ of using this F1 triggered technique adaptation strategy compared to optimal treatment geometry for all four fractions. Adjusting for the effect of internal target and OAR anatomy between fractions to more accurately reflect the doses actually delivered to these structures (Fig. 2), there was a 7.0 7.6 Gy ( p ! 0.018) increase in the F1þF3 anatomically corrected CTVHR D90% compared to the F1 anatomically corrected CTVHR D90% with adaptation and, again, no difference

Table 2 Summary of target and OAR dosimetry for the five planning scenarios Scenario

CTVHR D90%

F1 projected (mean SD) F1 anatomically corrected (mean SD) F1þF3 projected (mean SD) F1þF3 anatomically corrected (mean SD) F1-4 optimal (mean SD) F1 dosimetric uncertaintya (mean SD) F1þF3 dosimetric uncertaintyb (mean SD)

87 87 91 90 92 0.4 1.1

9.3 6.5 6.1 5.3 5.8 6.7 2.0

OAR 5 organ at risk. a F1 anatomically corrected dosedF1 projected dose. b F1þF3 anatomically corrected dosedF1þF3 projected dose.

Gy Gy Gy Gy Gy Gy Gy

Rectum D2cm3 66 68 66 66 67 2.1 0.14

7.2 7.7 6.3 7.4 7.2 4.3 4.8


Sigmoid D2cm3 65 65 64 65 65 0.08 0.78

9.7 8.4 9.3 8.8 8.6 4.8 3.1


Bladder D2cm3 83 84 82 82 83 0.48 0.26

9.8 9.8 9.8 8.9 8.2 3.9 2.7


90


Fig. 1. F3 projected CTVHR D90% vs. F1 projected CTVHR D90%. The closed symbols indicate patients in whom needles were added for the second insertion. The arrow indicates a patient where peer review on Day 1 identified ways to improve the plan without adapting the treatment geometry. The dark lines represent the EQD210 CTVHR D90% planning objective of 85 Gy. The dotted lines represent the line of unity.

(0.47 2.9 Gy) without adaptation. The CTVHR D90% planning objective was achieved in 85% of patients using the triggered technique adaptation strategy, and as shown in Fig. S1, the OAR planning objectives were achieved in 80% of patients. Daily MR imaging and planning It is assumed that MR imaging and planning is required immediately after each insertion (Fractions 1 and 3) to account for treatment technique adaptation and changes in tumor and OAR anatomy. The need for a second set of images with Fractions 2 and 4 to assure accurate estimation of dose to the target and OARs was evaluated by comparing the F1þF3 projected doses to the F1þF3 anatomically corrected doses. The F1þF3 projected CTVHR D90% and

Fig. 2. F1þF3 anatomically corrected CTVHR D90% vs. F1 anatomically corrected CTVHR D90%. The closed symbols indicate patients in whom needles were added for the second insertion. The dark lines represent the EQD210 CTVHR D90% planning objective of 85 Gy. The dotted lines represent the line of unity.

F1þF3 anatomically corrected CTVHR D90% were strongly correlated (r 5 0.95) as shown in Fig. 3, although the former systematically overestimated the latter by 1.1 2.0 Gy ( p 5 0.02). There were also moderate to strong correlations between the F1þF3 projected and F1þF3 anatomically corrected OAR D2cm3 values (rectum r 5 0.77, sigmoid r 5 0.94, bladder r 5 0.96) as shown in Fig. S2, and no systematic differences (rectum 0.14 4.8 Gy, [p 5 0.9], sigmoid 0.78 3.1 Gy [p 5 0.3], bladder 0.26 2.7 Gy [p 5 0.7]). There was 80% agreement between the two metrics in the identification of patients with optimal ($85 Gy) or suboptimal target dosimetry and 80%, 80%, and 100% agreement with respect to optimal/suboptimal rectum, sigmoid, and bladder dosimetry, respectively. The added benefit of plan reoptimization with Fractions 2 and 4 was evaluated by comparing the F1þF3 anatomically corrected dosimetry to the F1-4 optimal dosimetry (imaging and plan optimization before each fraction) (Fig. 4 and Fig. S3). The CTVHR D90% and OAR D2cm3 values were all very strong correlated (CTVHR r 5 0.95, rectum r 5 0.99, sigmoid r 5 0.99, bladder r 5 0.96), and there were no or very small systematic differences (CTVHR 1.5 1.8 Gy [p 5 0.001], rectum 0.31 1.1 Gy [p 5 0.2], sigmoid 0.42 1.2 Gy [p 5 0.1], bladder 0.57 2.5 Gy [p 5 0.3]). In none of the cases did plan reoptimization on Days 2 and 4 improve the target or OAR dosimetry sufficiently to shift from a suboptimal condition (below or above the planning objectives respective) to an optimal condition. Team learning MR images, contours, and treatment plans were reviewed during routine weekly peer-review quality assurance rounds (23) by an interdisciplinary team of experts

Fig. 3. F1þF3 anatomically corrected CTVHR D90% vs. F1þF3 projected CTVHR D90%. The closed symbols indicate patients in whom needles were added for the second insertion. The dark lines represent the EQD210 CTVHR D90% planning objective of 85 Gy. The dotted lines represent the line of unity and 5% of the CTVHR D90% planning objective.


Fig. 4. F1-4 optimal CTVHR D90% vs. F1þF3 anatomically corrected CTVHR D90%. The closed symbols indicate patients in whom needles were added for the second insertion. The dark lines represent the EQD210 CTVHR D90% planning objective of 85 Gy. The dotted lines represent the line of unity and 5% of the CTVHR D90% planning objective.

in gynecologic radiation oncology. There were at least two radiation oncologists and one medical physicist present each week, as well as radiation therapists, dosimetrists, and trainees. Most patients had images and/or plans reviewed at least four times during treatment: (1) EBRT contours and plan prior to the start of treatment, (2) MR images toward the end of EBRT (no applicator) to evaluate tumor response prior to brachytherapy and decide on applicator geometry for the first insertion, (3) Fractions 1 and 2 (Insertion 1) brachytherapy images, contours, and plans, and (4) Fractions 3 and 4 (Insertion 2) brachytherapy images, contours, and plans. Discussion focused on challenges during applicator insertion, contouring or planning, the appropriateness of the applicator geometry for the first insertion, the need to adapt the technique for the second insertion, and programmatic process changes to improve overall efficiency.

Discussion Despite growing evidence of improved pelvic control and survival as well as reduced toxicity with MRgBT (10e17), implementation can be challenging and uptake has been slow in a significant proportion of North American centers (19, 20). MRgBT represents a paradigm shift in the treatment of cervical cancer, often requiring retraining of radiation oncologists, medical physicists, and radiation therapists and the allocation of new or additional resources. Practitioner comfort and familiarity with the technique, access to MR prior to each fraction and overall process efficiency, have been cited as some of the challenges with implementing MRgBT at the programmatic level (18). Educational offering by the American Brachytherapy Society, the European Society for Radiation and Oncology, and others are important in translating knowledge to practice. However, at the programmatic level in many parts of North

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America (18e20), there is an ongoing need for guidance and tools to facilitate team learning in the context of efficient and safe transition from traditional brachytherapy practice to MRgBT. This study describes the learning process undertaken by our program during implementation of MRgBT for cervical cancer, including the adaptive use of interstitial needles, the strategic use of MR imaging and treatment planning, and team learning as a forum for change management. During early days of our MRgBT cervical cancer program, questions arose about the optimal use of interstitial needles, including: (1) which patients most benefit from needles with respect to tumor coverage and/or OAR sparing, (2) where should needles optimally be positioned and at what depths in relation to the intracavitary applicator and tumor/OAR anatomy, and (3) when is reimaging and replanning needed, balancing tumor coverage, and OAR sparing with process efficiency. To address these questions, the program adopted a graded implementation approach with a tandem/ring applicator only for the first insertion and technique adaptation with the addition of needles for the second insertion if necessary based on review of the initial dosimetry. This dosimetry triggered adaptive strategy resulted in large improvement in tumor dosimetry relative to intracavitary treatment alone in some patients without significantly compromising OAR sparing (Figs. 1 and 2), while allowed the team to build expertise and become comfortable with the benefits and optimal use of needles. It is acknowledged that, among patients requiring needles, the dosimetric advantages are greatest if they are used throughout treatment (all four brachytherapy fractions). It is also acknowledged that it may be more difficult to achieve the more rigorous EMBRACE II tumor and OAR planning objectives (24) without the use of interstitial needles throughout treatment. Nevertheless, this triggered, adaptive strategy allowed out team to gain valuable experience with the use of needles and develop a shared level of comfort with their use. Our practice evolved over the course of the study toward increased use of needles with the first insertion based on prospective review of MR images near the end of EBRT. This has continued and in 2016, 91% of our cervical cancer patients were treated with an intracavitary applicator and interstitial needles from the first fraction to optimize tumor coverage, OAR sparing, or both. The availability of MR imaging for radiation treatment planning is limited in many centers and a barrier to implementing cervical cancer MRgBT (18). MR imaging and planning prior to each brachytherapy fraction is demanding of other resources as well, including expert personnel, and can add considerably to the time required to deliver treatment (25). To evaluate the benefit vs. programmatic cost of more frequent MR imaging and planning, we compared three strategies: (1) imaging and planning only once per insertion (F1þF3 projected), (2) planning only once per insertion with daily imaging and dose accumulation to

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account for changes in target and OAR anatomy (F1þF3 anatomically adjusted), and (3) imaging and plan reoptimization prior to each fraction (F1-4 optimal). In general, the F1þF3 anatomically adjusted strategy improved the target and OAR dose reporting accuracy compared to the F1þF3 projected scenario, although the differences were small in most patients. There was little added benefit of daily plan reoptimization. Our findings are generally consistent with those previously reported (26, 27), showing strong dosimetric correlations among these approaches with small systematic and random differences. We conclude that MR imaging and planning once per insertion is a safe and efficient practice in most patients with little risk of compromising tumor coverage or OAR sparing. However, some form of volumetric imaging with MR, CT of ultrasound should be done immediately prior to each fraction to assure applicator placement stability and the absence of large interfraction changes in tumor or OAR anatomy. Cervical cancer MRgBT requires the interdisciplinary involvement of experienced radiation oncologists, medical physicists, and radiation therapists. As with the introduction of any new medical treatment, a coordinated approach that promotes learning is essential to optimize results and maintain patient safety. This can be achieved in different ways depending on program size and organization, staff commitment, and available learning resources. In our program, interdisciplinary peer review of all radical radiotherapy plans prior to the start of treatment is a priority activity intended to improve quality of care and prevent errors (23). We capitalized on our weekly gynecologic radiation oncology peer-review rounds to build individual and team competencies in cervical cancer MRgBT. For each patient, MR images and treatment plans were discussed in a collegial and nonthreatening manner with respect to challenges during applicator insertion or planning and the need for technique adaptation or process modification. The entire team benefited from our collective programmatic experience rather than from personal experience alone, an important consideration when dealing with a relatively uncommon disease like cervical cancer. We continue to review all cervical cancer patients as a team several times during treatment to assure best-practice management and continued process improvement. In addition, we are engaged in ‘‘communities of practice’’ in the province of Ontario and across Canada to enable large-scale learning about cervical cancer MRgBT and promote its widespread availability.

Conclusion MRgBT for cervical cancer represents a paradigm shift in the treatment of cervical cancer with the potential to substantially improve clinical outcomes. However, it is demanding of resources and associated with a steep

learning curve affecting all members of the treatment team. A graded implementation strategy with embedded learning and process improvement over time is one approach to achieving optimal results while maintaining patient safety. Technique adaptation based on the initial dosimetry is an efficient and safe approach to implementing MRgBT while gaining comfort with the use of needles. MR imaging and planning once per insertion is safe in most patients as long as applicator shifts, and large anatomical changes are excluded. Team learning through peer review, communities of practice, or other interactive forums is essential to building individual and programmatic competency.

Acknowledgments The authors thank the present and past members of the interdisciplinary Radiation Medicine gynecologic site group for their contributions to this work and their efforts to develop MR-guided intracavitary and interstitial brachytherapy for patients with cervical cancer.

Supplementary data Supplementary data related to this article can be found at https://doi.org/10.1016/j.brachy.2017.11.010. References [1] Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359eE386. [2] Hanna TP, Shafiq J, Delaney GP, et al. The population benefit of radiotherapy for cervical cancer: Local control and survival estimates for optimally utilized radiotherapy and chemoradiation. Radiother Oncol 2015;114:389e394. [3] Han K, Milosevic M, Fyles A, et al. Trends in the utilization of brachytherapy in cervical cancer in the United States. Int J Radiat Oncol Biol Phys 2013;87:111e119. [4] Hellebust TP, Kirisits C, Berger D, et al. Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group: Considerations and pitfalls in commissioning and applicator reconstruction in 3D image-based treatment planning of cervix cancer brachytherapy. Radiother Oncol 2010;96:153e160. [5] Petric P, Dimopoulos J, Kirisits C, et al. Inter- and intraobserver variation in HR-CTV contouring: Intercomparison of transverse and paratransverse image orientation in 3D-MRI assisted cervix cancer brachytherapy. Radiother Oncol 2008;89:164e171. [6] Viswanathan AN, Beriwal S, De Los Santos JF, et al. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part II: High-dose-rate brachytherapy. Brachytherapy 2012;11:47e52. [7] Viswanathan AN, Dimopoulos J, Kirisits C, et al. Computed tomography versus magnetic resonance imaging-based contouring in cervical cancer brachytherapy: Results of a prospective trial and preliminary guidelines for standardized contours. Int J Radiat Oncol Biol Phys 2007;68:491e498. [8] Tanderup K, Georg D, Potter R, et al. Adaptive management of cervical cancer radiotherapy. Semin Radiat Oncol 2010;20:121e129. [9] Tanderup K, Nielsen SK, Nyvang GB, et al. From point A to the sculpted pear: MR image guidance significantly improves tumour


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