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Cervical cancer brachytherapy in Canada: A focus on interstitial brachytherapy utilization
Brachytherapy
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(2016)
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Cervical cancer brachytherapy in Canada: A focus on interstitial brachytherapy utilization Amandeep S. Taggar1, Tien Phan2, Laurel Traptow2, Robyn Banerjee2, Corinne M. Doll2,* 2
1 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY Department of Oncology, Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada
ABSTRACT
PURPOSE: Brachytherapy (BT) techniques for cervical cancer in Canada have changed over the last decade, with evolution to high-dose-rate and image-guided BT. However, there are currently no national data on the use of interstitial BT (IBT). The purpose of this study was to document IBT utilization in Canadian centers, as well as update details of cervical cancer BT practices. METHODS AND MATERIALS: All Canadian centers with gynecologic BT services (n 5 33) were identified, and one gynecology radiation oncologist per center was sent a 33-item e-mail questionnaire regarding their center’s practice for cervical cancer BT in 2015. Responses were reported and compared with practice patterns identified in a 2012 Canadian survey. RESULTS: The response rate was 85% (28/33 centers). The majority (93%) of respondents used high-dose-rate BT, similar to the 2012 survey; 96% of centers had transitioned to three-dimensional (MRI/CT)ebased planning in 2015 vs. 75% in 2012 ( p 5 0.03); 57% centers incorporated MRI for treatment planning in 2015 compared to 38% in 2012 ( p 5 0.15); the majority (13/16) using a combination of MRI and CT; 50% (14/28 centers) had the capacity to perform IBT, whereas 71% of those that did not referred patients to other centers. Of centers performing IBT, the majority (11/ 14) used template-based techniques with a median of 6 (range 2e20) needles/catheters and an average of 4 (range 1e5) fractions. Catheters were placed using: strategy based on pre-op imaging (21%), intra-op ultrasound (50%), intra-op MRI (7%), and intra-op CT (21%). The most common dose/fractionation schedules were 6 Gy 5 fractions (40%), 8 Gy 3 fractions (19%), and 7 Gy 4 fractions (15%). CONCLUSIONS: In Canada, treatment of cervical cancer continues to evolve. IBT has been adopted by half of the responding centers. As more centers move to MRI-based image-guided treatment planning, IBT will become an even more integral part of cervical cancer treatment. Ó 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Keywords:
Cervical cancer; Interstitial brachytherapy; Utilization; Practice pattern
Introduction Brachytherapy (BT) is an essential component of cervical cancer treatment. A surveillance, epidemiology and end results database report found that the cause-specific survival and overall survival were higher for women whose treatment included BT compared to matched cohorts who did not (1). Received 28 August 2016; received in revised form 17 October 2016; accepted 31 October 2016. Financial disclosure: None. Conflicts of interest: None. * Corresponding author. Department of Oncology, Tom Baker Cancer Center, University of Calgary, 1331 29th Street NW, Calgary, AB T2N 4N2, Canada. Tel.: 1-403-521-3095; fax: 1-403-283-1651. E-mail address: [email protected] (C.M. Doll).
Cervical cancer BT practice in Canada has rapidly changed over the last decade. Three-dimensional (3D) image-guided BT (IGBT) has been widely adopted after the publication of the joint American Brachytherapy Society (ABS) and Groupe Europeen de Curietherapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO) recommendations (2e4). MRI-based planning for at least part of the BT treatment has become common. High dose rate (HDR) had largely replaced low-dose-rate BT. These changes were documented in previous patterns-ofpractice surveys from Canada (5, 6) and the United States (7e9). The use of interstitial BT (IBT) for cervical cancer in Canadian practice has not been assessed. IGBT improves dose delivery in cervical cancer and improves sparing of organs at risk (10). In 2012, ABS issued
1538-4721/$ - see front matter Ó 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.brachy.2016.10.009
A.S. Taggar et al. / Brachytherapy
guidelines recommending the use of interstitial needles for cervical cancer (11). The GEC-ESTRO also published similar recommendations and numerous reports on use of interstitial needles (12, 13). There are currently no national data on the use of IBT in the management of patients with cervical cancer. The purpose of this survey was to document IBT utilization in Canadian centers, as well as to update details of cervical cancer BT practices. The hypothesis was that the majority of Canadian cancer centers have adopted IBT for cervical cancer.
Methods and materials All Canadian cancer centers with gynecologic BT services (n 5 33) were identified from the website of Canadian Association of Radiation Oncology (www.caro-acro.org), personal communication with the Canadian Brachytherapy Group president, and individual phone calls. A 33-item questionnaire, designed using SurveyMonkey (www. surveymonkey.com Palo Alto, CA) was sent to one representative radiation oncologist per center who performed BT for gynecologic cancers. A reminder e-mail was sent 2 weeks later to all invitees if they had not responded. Questions were focused on radical, curative-intent treatment of the intact cervix using external beam radiotherapy and BT. Results were tabulated and compared to 2012 survey using SurveyMonkey and Microsoft (Seattle, WA) Excel software. Responses were compared using chi-square proportional analysis and p-values reported where appropriate. Results were analyzed in aggregate, although the respondents were not anonymized. All data were collected in accordance with the Health Information Act of Alberta after ethical review using the Alberta Research Ethics Community Consensus Initiative method (14).
Results The survey was conducted between December 2015 and January 2016. Twenty-eight out of 33 invitees completed the survey (response rate 85%). Twenty-seven out of 28 centers were using HDR and one center used pulsed-dose-rate BT. Imaging modality for insertion, volume delineation, and planning Fourteen of 28 (50%) centers were using in-suite imaging for BT compared to 10 of 24 (42%) centers in 2012 ( p 5 0.40). The number of centers moving patients to a diagnostic imaging department for imaging was similar, 7/28 (25%) in 2015 vs. 7/24 (29%) in 2012. Two centers had a dedicated magnetic resonance imaging unit within the BT suite in 2015, compared to none in 2012. Twenty-one (75%) centers used ultrasound (US) as image guidance for insertion of the BT applicators. Most
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centers used a transpelvic/abdominal technique; two centers (7%) used a transrectal US. The proportion of centers that were using 3D planning increased to 96% (27/28) in 2015 compared to 75% (18/24) in 2012 ( p 5 0.03), and the number of centers utilizing two-dimensional imaging (x-rays/orthogonal films) for planning decreased (1/28 centers) Fig. 1. The number of centers that obtain MRI for at least the first fraction, with applicator in place, for treatment planning continues to increase; 57% (16/28) in 2015 compared to 38% (9/24) in 2012 ( p 5 0.15). Four out of 16 centers that used MRI for volume delineation used it for all the fractions, whereas all centers (16/16) used it for at least the first insertion and the remainder of the fractions were delivered using CT guidance. The number of centers that contoured high-risk clinical target volume (HR CTV) increased from 15/24 (63%) in 2012 to 21/28 (75%) in 2015 ( p 5 0.33). Interstitial BT Table 1 summarizes the use of IBT in Canada in 2015. Fourteen of 28 responding centers had the ability to treat patients with cervical cancer with IBT. Ten out of 14 (71%) centers that did not have the ability to perform IBT referred their patients to other centers, if deemed eligible for IBT by the treating physician. Although the data presented are in aggregate form, examination of individual responses revealed that majority of the centers performing IBT were larger centers directly affiliated with academic institutions. The ability to perform IBT in a center was related to MRI-based planning capability; 10 of the 14 (71%) IBT-capable centers also used MRI-based planning; 50% (7/14) of respondents with IBT at their center used it for more than 25% of patients. Eleven (79%) respondents performing IBT determined its utility based on disease extent at the time of BT as well as imaging studies performed at the time of diagnosis and just before BT. In terms of IBT technique, 9 of 14 (64%) respondents performing IBT used a free-hand, template-based technique only, whereas two (14%) centers the have capability of 1
2012 (N=24)
0.9 Proportion of responding centers
2
2015 (N=28)
0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 X-rays
Cone beam CT
CT imaging
MR imaging
Ultrasound
Fig. 1. Imaging used for cervix cancer brachytherapy planning in 2012 (n 5 24) and 2015 (n 5 28) across Canada.
A.S. Taggar et al. / Brachytherapy
50 71
21
Proportion of responding centers
% Respondents (total n 5 28)
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3
0.5 0.4 0.3 0.2 0.1
0 36 7 14 21 21 14 65 21 50 7 21
BT 5 brachytherapy. a The numbers add to 99% due to rounding.
performing either free-hand template-based IBT or using hybrid applicators such as Vienna or Utrecht types (Elekta Instruments AB Stockholm, Sweden). Only three (21%) centers solely used hybrid applicators. Intra-op US (8/14, 57%) was most the commonly used imaging modality for guiding needle placement; other imaging modalities included intra-op MRI (1/14) and intra-op CT (3/14), whereas 3 out of 14 centers did not use any real-time image guidance. The median (range) number of needles used for IBT was 6 (2e20). For treatment planning, 11 out of 14 (79%) respondents used inverse treatment planning system (TPS), two respondents do not have inverse TPS, and one respondent was unaware of the TPS used at their center. Seven of 14 (50%) respondents performed IBT as an outpatient procedure and used separate insertions for each fraction; three (21%) respondents admitted patients for treatment and delivered multiple fractions with a single insertion; four (29%) respondents treated patients as inpatients but used separate insertions for each fraction (Fig. 2). Five out of 14 respondents (36%) use four fractions for interstitial implants, whereas other common fractionation schemes were as follows: 5 (29%), 3 (21%), and 6 (7%). One of the respondents (7%) used single fraction pulsed dose rate for IBT.
0 As an in-patient, single As an in-patient, multiple insertion insertions
As an out-patient, multiple insertions
Fig. 2. Interstitial brachytherapy delivery across Canadian centers.
between 2012 and 2015. In 2012, 6 of 24 (25%) of centers did not contour any of the volumes (gross tumor volume, HR CTV, intermediate risk, bladder, rectum, or sigmoid colon) compared to just 1 of 28 (4%) centers in 2015 ( p 5 0.02). The proportion of centers that prescribed to HR CTV also increased from 12.5% (3/24) in 2012 to 50% (14/28) in 2015 ( p 5 0.004, Fig. 3). The proportion of centers that reported dose to the gross tumor volume, HR CTV, or both also increased from 83% in 2012 to 96% in 2015 ( p 5 0.12). There were a variety of dose and fractionation schedules used for cervical cancer BT in 2015. These are summarized in Table 2. The most common dose and fractionation regimen for both early and advanced stage cervical cancer was 6 Gy 5 fractions.
Discussion BT is the most effective way to deliver a high dose of conformal radiation therapy and is recommended for all cases of localized cervical cancer after external beam radiation. The objective of the current survey was to document patterns of care for cervical cancer BT in Canadian cancer centers in 2015 and assess changes in practice compared to 1 Proportion of responding centers
Number of Canadian centers in 2015 using IBT (n 5 14) Number of centers that did not use IBT but referred patients to another center for IBT (n 5 10 out 14) Selection of patients for IBT (n 5 14) Based on disease extent/imaging at the time of diagnosis Based on disease extent/imaging before BT Based on disease extent/imaging at the time of BT Based on disease extent/imaging at diagnosis and before BT Based on disease extent/imaging before BT and at the time of BT Based on all three criteria IBT technique available at responding centers (n 5 14) Hybrid applicator (Vienna or Utrecht type) only Hybrid applicator or free-hand template-based needle insertion Free-hand template-based only Guidance used for needle placement (n 5 14)a Strategy based on pre-op imaging alone Intra-op ultrasound Intra-op MR Intra-op CT
(2016)
0.6
Table 1 Interstitial brachytherapy (IBT) practice across Canada IBT Practice Details
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0.9
2012 (N=24)
0.8
2015 (N=28)
0.7 0.6
*
0.5 0.4 0.3 0.2 0.1 0
Volumes, dose, and fractionation Across Canada, there was a notable increase in the proportion of centers that performed volume-based BT
HR CTV
HR CTV, but using Point A as a reference
Point A
Fig. 3. Dose prescription practices across various centers in Canada. *p 5 0.004, chi-square. HR CTV 5 high-risk clinical target volume.
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A.S. Taggar et al. / Brachytherapy
Table 2 Dose and fractionation for cervix cancer HDR brachytherapy in Canada in 2015 Dose and fractionation by stage category Early stage (IBeIIA)a 6 Gy 5 8 Gy 3 7 Gy 4 5.5 Gy 5 6.5 Gy 5 5 Gy 5 6.75 Gy 4 PDR Advanced stage (IIBeIII)b 6 Gy 5 8 Gy 3 7 Gy 4 5.5 Gy 5 7.5 Gy 3 PDR
Crude total dose (Gy)
Total dose (2 Gy Eq, a/b 5 10)
% Respondents
30 24 28 27.5 26 25 27 35
40.0 36.0 39.7 35.5 35.8 31.3 37.7 35.0
37 19 15 11 7 4 4 4
30 24 28 27.5 22.5 40e45
40.0 36.0 39.7 35.5 32.8 40e45
52 19 15 7 4 4
PDR 5 pulsed dose rate; HDR 5 high dose rate; EBRT 5 external beam radiotherapy. a 96% of respondents combine above HDR regimen with 45 Gy/25 fractions EBRT and 4% combine it with 46 Gy/23 fractions. b 52% of respondents combine above HDR regimens with 45 Gy/25 fractions EBRT, 22% combine with 50.4 Gy/28 fractions, 15% combine it with range of 45e50 Gy/25 fractions, and 11% combine it with 50 Gy/25 fractions.
prior surveys conducted in 2012. Prior surveys documented the shift from low-dose-rate to HDR BT and the transition from two-dimensional to 3D planning and treatment delivery within Canadian centers (5, 6). The current survey added questions to assess the use of IBT practice across Canada. This survey affirms that a majority of the responding centers use HDR BT. At the time of this survey, 3D image guidance has become standard for BT within Canadian centers as 27 out of 28 respondents reported using either CT, MRI, or a combination of both CT and MRI for applicator insertion, treatment planning, and delivery. Many studies have reported an improvement in dosimetry and clinical outcomes with MRI-based treatment planning (13, 15, 16). Only 1 out of 28 centers continue to use orthogonal x-rays as the primary modality for BT. This finding is similar to that observed in the United States by Grover et al. (7). We postulate that this overall shift may translate into an improvement in cervical cancer outcomes on a national basis in Canada. An increase in availability of in-suite imaging was observed in the current survey compared to the 2012 survey. There is an increase in the number of centers in the United States and worldwide that have adopted in-suite imaging techniques, such as US, cone-beam CT, CT on rails and MRI to assist with applicator insertion, interstitial needle placement, volume delineation, and treatment planning (9, 17, 18). This is also reflected in the ABS practice pattern
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survey conducted in 2014 (7). Precision in applicator and needle placement not only improves clinical outcomes, but also decreases the rate of acute complications (19). IBT is crucial for providing adequate dose to large tumors that cannot be encompassed with standard intracavitary applicators to ensure good clinical outcome (20e29) while keeping the dose to normal organs low (30). No previous data are available on implementation and utilization of IBT in Canada. Patterns of care analyses have shown a decline in the use of IBT in the United States (31). These studies were performed before the widespread commercial availability of hybrid interstitial applicators. It is likely that the availability of these applicators combined with increased use of 3D image-guided planning will reverse this trend. This survey shows that, in Canada, hybrid applicators are being increasingly used (5/28 centers), and there remains a strong tradition in the use of interstitial templatebased BT as well (11/28 centers). These techniques are complementary. Hybrid applicators can typically extend the HR CTV coverage by up to 1 cm laterally without compromising organs at risk dose compared to standard intracavitary applicators (24). Where extensive lateral or vaginal disease remains after external beam radiation, interstitial template-based treatment is preferred. MRI guidance is essential in performing IBT, as described by GECESTRO and ABS guidelines (3, 32). This survey confirms that in Canada, centers that have improved access to MRI planning (using either in-suite or the local diagnostic imaging department) are performing IBT. Improvement in BT techniques and increased availability of image guidance as well as interstitial techniques have renewed interest in BT. One, however, must be cautious in recommending BT to be universally available at all centers treating gynecologic cancer, especially IBT. Compton et al. (33) published a survey of Accreditation Council for Graduation Medical Education recognized radiation oncology programs in the United States in 2013 and reported a significant decline in the resident experience with IBT. A 2015 Canadian national survey of practicing radiation oncologists, residents, and fellows concluded that there is a need for development of BT-specific curriculum and a credentialing process (34). That survey asked residents and fellows about their satisfaction regarding training in cervical cancer intracavitary BT and IBT; 70% respondents were satisfied with intracavitary BT teaching, whereas less than 10% felt satisfied with IBT teaching/training. More than 90% of respondents were either dissatisfied or neutral in regards to IBT teaching, and more than 70% of respondents had no competency or exposure to IBT for cervix cancer. Ultimately, this deficiency in training and exposure results in lack of confidence in offering or performing BT by the radiation oncologists after they finish training. The current survey found that 50% of the Canadian centers performing BT for patients with cervical cancer provided IBT and most of those centers were directly affiliated with academic institutions. This may be an
A.S. Taggar et al. / Brachytherapy
appropriate balance in Canada at this time, with additional centers introducing IBT program in the coming years as they develop expertise and resources to perform these procedures. A multidisciplinary team including radiation oncologists, medical physicists and dosimetrists with specialty training in BT, gynecology oncologists, body radiologists, MRI treatment planning capability and appropriate operating room, in-patient, and nursing support services are essential in order for a center to effectively perform IBT procedures. Limitations This is a retrospective audit of BT practices within Canadian centers. Nonetheless, it provides important information that can help guide future national/international guidelines and clinical trials. Furthermore, the response rate, though excellent, was not complete. Conclusions In Canada, treatment of cervical cancer continues to evolve. IBT has been adopted by half of the responding centers. As more centers move to MRI-based image-guided treatment planning, IBT will become an even more integral part of cervical cancer treatment.
Acknowledgments The authors thank Dr. Marc Gaudet, Dr. Boris Bahoric, and the Canadian Brachytherapy Group for their assistance and support of this survey. References [1] 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. [2] Nag S, Cardenes H, Chang S, et al. Proposed guidelines for imagebased intracavitary brachytherapy for cervical carcinoma: Report from Image-Guided Brachytherapy Working Group. Int J Radiat Oncol Biol Phys 2004;60:1160e1172. [3] P€ otter R, Haie-Meder C, Van Limbergen E, et al. Recommendations from gynaecological (GYN) GEC ESTRO working group (II): Concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology. Radiother Oncol 2006;78:67e77. [4] Haie-Meder C, P€ otter R, Van Limbergen E, et al. Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): Concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005;74:235e245. [5] Phan T, Mula-Hussain L, Pavamani S, et al. The changing landscape of brachytherapy for cervical cancer: A Canadian practice survey. Curr Oncol 2015;22:356e360. [6] Pearce A, Craighead P, Kay I, et al. Brachytherapy for carcinoma of the cervix: A Canadian survey of practice patterns in a changing era. Radiother Oncol 2009;91:194e196.
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[7] Grover S, Harkenrider MM, Cho LP, et al. Image guided cervical brachytherapy: 2014 survey of the American Brachytherapy Society. Int J Radiat Oncol Biol Phys 2016;94:598e604. [8] Viswanathan AN, Creutzberg CL, Craighead P, et al. International brachytherapy practice patterns: A survey of the Gynecologic Cancer Intergroup (GCIG). Int J Radiat Oncol Biol Phys 2012;82:250e255. [9] Viswanathan AN, Erickson BA. Three-dimensional imaging in gynecologic brachytherapy: A survey of the American Brachytherapy Society. Int J Radiat Oncol Biol Phys 2010;76:104e109. [10] Kirisits C, Lang S, Dimopoulos J, et al. The Vienna applicator for combined intracavitary and interstitial brachytherapy of cervical cancer: Design, application, treatment planning, and dosimetric results. Int J Radiat Oncol Biol Phys 2006;65:624e630. [11] 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. [12] Fokdal L, Tanderup K, Hokland SB, et al. Clinical feasibility of combined intracavitary/interstitial brachytherapy in locally advanced cervical cancer employing MRI with a tandem/ring applicator in situ and virtual preplanning of the interstitial component. Radiother Oncol 2013;107:63e68. [13] Rijkmans EC, Nout RA, Rutten IHH, et al. Improved survival of patients with cervical cancer treated with image-guided brachytherapy compared with conventional brachytherapy. Gynecol Oncol 2014; 135:231e238. [14] Hagen B, O’Beirne M, Desai S, et al. Innovations in the ethical review of health-related quality improvement and Research: The Alberta Research Ethics community consensus initiative (ARECCI). Healthc Policy 2007;2:e164ee177. [15] Lindegaard JC, Tanderup K, Nielsen SKK, et al. MRI-guided 3D optimization significantly improves DVH parameters of pulseddose-rate brachytherapy in locally advanced cervical cancer. Int J Radiat Oncol Biol Phys 2008;71:756e764. [16] Tanderup K, Nielsen SKK, Nyvang G-BB, et al. From point A to the sculpted pear: MR image guidance significantly improves tumour dose and sparing of organs at risk in brachytherapy of cervical cancer. Radiother Oncol 2010;94:173e180. [17] Orcutt KP, Libby B, Handsfield LL, et al. CT-on-rails-guided HDR brachytherapy: Single-room, rapid-workflow treatment delivery with integrated image guidance. Future Oncol 2014;10:569e575. [18] Kapur T, Egger J, Damato A, et al. 3-T MR-guided brachytherapy for gynecologic malignancies. Magn Reson Imaging 2012;30:1279e1290. [19] Banerjee R, Kamrava M. Brachytherapy in the treatment of cervical cancer: A review. Int J Women’s Health 2014;6:555. [20] Mahantshetty U, Shrivastava S, Kalyani N, et al. Template-based high-dose-rate interstitial brachytherapy in gynecologic cancers: A single institutional experience. Brachytherapy 2014;13:337e342. [21] Beriwal S, Bhatnagar A, Heron DE, et al. High-dose-rate interstitial brachytherapy for gynecologic malignancies. Brachytherapy 2006;5: 218e222. [22] Syed AM, Puthawala AA, Abdelaziz NN, et al. Long-term results of low-dose-rate interstitial-intracavitary brachytherapy in the treatment of carcinoma of the cervix. Int J Radiat Oncol Biol Phys 2002;54:67e78. [23] Pinn-Bingham M, Puthawala AA, Syed AM, et al. Outcomes of highdose-rate interstitial brachytherapy in the treatment of locally advanced cervical cancer: Long-term results. Int J Radiat Oncol Biol Phys 2013;85:714e720. [24] Dimopoulos JC, Kirisits C, Petric P, et al. The Vienna applicator for combined intracavitary and interstitial brachytherapy of cervical cancer: Clinical feasibility and preliminary results. Int J Radiat Oncol Biol Phys 2006;66:83e90. [25] P€otter R, Georg P, Dimopoulos JC, et al. Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer. Radiother Oncol 2011;100: 116e123.
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[26] Beriwal S, Kannan N, Kim H, et al. Three-dimensional high dose rate intracavitary image-guided brachytherapy for the treatment of cervical cancer using a hybrid magnetic resonance imaging/computed tomography approach: Feasibility and early results. Clin Oncol (R Coll Radiol) 2011;23:685e690. [27] Nomden CN, de Leeuw AA, Roesink JM, et al. Clinical outcome and dosimetric parameters of chemo-radiation including MRI guided adaptive brachytherapy with tandem-ovoid applicators for cervical cancer patients: A single institution experience. Radiother Oncol 2013;107:69e74. [28] Yoshida K, Yamazaki H, Takenaka T, et al. Preliminary results of MRI-assisted high-dose-rate interstitial brachytherapy for uterine cervical cancer. Brachytherapy 2015;14:1e8. [29] Mesko S, Swamy U, Park S-JJ, et al. Early clinical outcomes of ultrasound-guided CT-planned high-dose-rate interstitial brachytherapy for primary locally advanced cervical cancer. Brachytherapy 2015;14:626e632.
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[30] Bansal AK, Semwal MK, Sharma DN, et al. A patient-based dosimetric study of intracavitary and interstitial brachytherapy in advanced stage carcinoma of the cervix. J Appl Clin Med Phys 2014;15:4509. [31] Eifel P, Ho A, Khalid N, et al. Patterns of radiation therapy practice for patients treated for intact cervical Cancer in 2005 to 2007: A quality research in radiation oncology study. Int J Radiat Oncol Biol Phys 2014;89:249e256. [32] Lee L, Das I, Higgins S, et al. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part III: Low-dose-rate and pulsed-dose-rate brachytherapy. Brachytherapy 2012;11:53e57. [33] Compton JJ, Gaspar LE, Shrieve DC, et al. Resident-reported brachytherapy experience in ACGME-accredited radiation oncology training programs. Brachytherapy 2013;12:622e627. [34] Gaudet M, Jaswal J, Keyes M. Current state of brachytherapy teaching in Canada: A national survey of radiation oncologists, residents, and fellows. Brachytherapy 2015;14:197e201.
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Cervical cancer brachytherapy in Canada: A focus on interstitial brachytherapy utilization Amandeep S. Taggar1, Tien Phan2, Laurel Traptow2, Robyn Banerjee2, Corinne M. Doll2,* 2
1 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY Department of Oncology, Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada
ABSTRACT
PURPOSE: Brachytherapy (BT) techniques for cervical cancer in Canada have changed over the last decade, with evolution to high-dose-rate and image-guided BT. However, there are currently no national data on the use of interstitial BT (IBT). The purpose of this study was to document IBT utilization in Canadian centers, as well as update details of cervical cancer BT practices. METHODS AND MATERIALS: All Canadian centers with gynecologic BT services (n 5 33) were identified, and one gynecology radiation oncologist per center was sent a 33-item e-mail questionnaire regarding their center’s practice for cervical cancer BT in 2015. Responses were reported and compared with practice patterns identified in a 2012 Canadian survey. RESULTS: The response rate was 85% (28/33 centers). The majority (93%) of respondents used high-dose-rate BT, similar to the 2012 survey; 96% of centers had transitioned to three-dimensional (MRI/CT)ebased planning in 2015 vs. 75% in 2012 ( p 5 0.03); 57% centers incorporated MRI for treatment planning in 2015 compared to 38% in 2012 ( p 5 0.15); the majority (13/16) using a combination of MRI and CT; 50% (14/28 centers) had the capacity to perform IBT, whereas 71% of those that did not referred patients to other centers. Of centers performing IBT, the majority (11/ 14) used template-based techniques with a median of 6 (range 2e20) needles/catheters and an average of 4 (range 1e5) fractions. Catheters were placed using: strategy based on pre-op imaging (21%), intra-op ultrasound (50%), intra-op MRI (7%), and intra-op CT (21%). The most common dose/fractionation schedules were 6 Gy 5 fractions (40%), 8 Gy 3 fractions (19%), and 7 Gy 4 fractions (15%). CONCLUSIONS: In Canada, treatment of cervical cancer continues to evolve. IBT has been adopted by half of the responding centers. As more centers move to MRI-based image-guided treatment planning, IBT will become an even more integral part of cervical cancer treatment. Ó 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Keywords:
Cervical cancer; Interstitial brachytherapy; Utilization; Practice pattern
Introduction Brachytherapy (BT) is an essential component of cervical cancer treatment. A surveillance, epidemiology and end results database report found that the cause-specific survival and overall survival were higher for women whose treatment included BT compared to matched cohorts who did not (1). Received 28 August 2016; received in revised form 17 October 2016; accepted 31 October 2016. Financial disclosure: None. Conflicts of interest: None. * Corresponding author. Department of Oncology, Tom Baker Cancer Center, University of Calgary, 1331 29th Street NW, Calgary, AB T2N 4N2, Canada. Tel.: 1-403-521-3095; fax: 1-403-283-1651. E-mail address: [email protected] (C.M. Doll).
Cervical cancer BT practice in Canada has rapidly changed over the last decade. Three-dimensional (3D) image-guided BT (IGBT) has been widely adopted after the publication of the joint American Brachytherapy Society (ABS) and Groupe Europeen de Curietherapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO) recommendations (2e4). MRI-based planning for at least part of the BT treatment has become common. High dose rate (HDR) had largely replaced low-dose-rate BT. These changes were documented in previous patterns-ofpractice surveys from Canada (5, 6) and the United States (7e9). The use of interstitial BT (IBT) for cervical cancer in Canadian practice has not been assessed. IGBT improves dose delivery in cervical cancer and improves sparing of organs at risk (10). In 2012, ABS issued
1538-4721/$ - see front matter Ó 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.brachy.2016.10.009
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guidelines recommending the use of interstitial needles for cervical cancer (11). The GEC-ESTRO also published similar recommendations and numerous reports on use of interstitial needles (12, 13). There are currently no national data on the use of IBT in the management of patients with cervical cancer. The purpose of this survey was to document IBT utilization in Canadian centers, as well as to update details of cervical cancer BT practices. The hypothesis was that the majority of Canadian cancer centers have adopted IBT for cervical cancer.
Methods and materials All Canadian cancer centers with gynecologic BT services (n 5 33) were identified from the website of Canadian Association of Radiation Oncology (www.caro-acro.org), personal communication with the Canadian Brachytherapy Group president, and individual phone calls. A 33-item questionnaire, designed using SurveyMonkey (www. surveymonkey.com Palo Alto, CA) was sent to one representative radiation oncologist per center who performed BT for gynecologic cancers. A reminder e-mail was sent 2 weeks later to all invitees if they had not responded. Questions were focused on radical, curative-intent treatment of the intact cervix using external beam radiotherapy and BT. Results were tabulated and compared to 2012 survey using SurveyMonkey and Microsoft (Seattle, WA) Excel software. Responses were compared using chi-square proportional analysis and p-values reported where appropriate. Results were analyzed in aggregate, although the respondents were not anonymized. All data were collected in accordance with the Health Information Act of Alberta after ethical review using the Alberta Research Ethics Community Consensus Initiative method (14).
Results The survey was conducted between December 2015 and January 2016. Twenty-eight out of 33 invitees completed the survey (response rate 85%). Twenty-seven out of 28 centers were using HDR and one center used pulsed-dose-rate BT. Imaging modality for insertion, volume delineation, and planning Fourteen of 28 (50%) centers were using in-suite imaging for BT compared to 10 of 24 (42%) centers in 2012 ( p 5 0.40). The number of centers moving patients to a diagnostic imaging department for imaging was similar, 7/28 (25%) in 2015 vs. 7/24 (29%) in 2012. Two centers had a dedicated magnetic resonance imaging unit within the BT suite in 2015, compared to none in 2012. Twenty-one (75%) centers used ultrasound (US) as image guidance for insertion of the BT applicators. Most
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centers used a transpelvic/abdominal technique; two centers (7%) used a transrectal US. The proportion of centers that were using 3D planning increased to 96% (27/28) in 2015 compared to 75% (18/24) in 2012 ( p 5 0.03), and the number of centers utilizing two-dimensional imaging (x-rays/orthogonal films) for planning decreased (1/28 centers) Fig. 1. The number of centers that obtain MRI for at least the first fraction, with applicator in place, for treatment planning continues to increase; 57% (16/28) in 2015 compared to 38% (9/24) in 2012 ( p 5 0.15). Four out of 16 centers that used MRI for volume delineation used it for all the fractions, whereas all centers (16/16) used it for at least the first insertion and the remainder of the fractions were delivered using CT guidance. The number of centers that contoured high-risk clinical target volume (HR CTV) increased from 15/24 (63%) in 2012 to 21/28 (75%) in 2015 ( p 5 0.33). Interstitial BT Table 1 summarizes the use of IBT in Canada in 2015. Fourteen of 28 responding centers had the ability to treat patients with cervical cancer with IBT. Ten out of 14 (71%) centers that did not have the ability to perform IBT referred their patients to other centers, if deemed eligible for IBT by the treating physician. Although the data presented are in aggregate form, examination of individual responses revealed that majority of the centers performing IBT were larger centers directly affiliated with academic institutions. The ability to perform IBT in a center was related to MRI-based planning capability; 10 of the 14 (71%) IBT-capable centers also used MRI-based planning; 50% (7/14) of respondents with IBT at their center used it for more than 25% of patients. Eleven (79%) respondents performing IBT determined its utility based on disease extent at the time of BT as well as imaging studies performed at the time of diagnosis and just before BT. In terms of IBT technique, 9 of 14 (64%) respondents performing IBT used a free-hand, template-based technique only, whereas two (14%) centers the have capability of 1
2012 (N=24)
0.9 Proportion of responding centers
2
2015 (N=28)
0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 X-rays
Cone beam CT
CT imaging
MR imaging
Ultrasound
Fig. 1. Imaging used for cervix cancer brachytherapy planning in 2012 (n 5 24) and 2015 (n 5 28) across Canada.
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50 71
21
Proportion of responding centers
% Respondents (total n 5 28)
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3
0.5 0.4 0.3 0.2 0.1
0 36 7 14 21 21 14 65 21 50 7 21
BT 5 brachytherapy. a The numbers add to 99% due to rounding.
performing either free-hand template-based IBT or using hybrid applicators such as Vienna or Utrecht types (Elekta Instruments AB Stockholm, Sweden). Only three (21%) centers solely used hybrid applicators. Intra-op US (8/14, 57%) was most the commonly used imaging modality for guiding needle placement; other imaging modalities included intra-op MRI (1/14) and intra-op CT (3/14), whereas 3 out of 14 centers did not use any real-time image guidance. The median (range) number of needles used for IBT was 6 (2e20). For treatment planning, 11 out of 14 (79%) respondents used inverse treatment planning system (TPS), two respondents do not have inverse TPS, and one respondent was unaware of the TPS used at their center. Seven of 14 (50%) respondents performed IBT as an outpatient procedure and used separate insertions for each fraction; three (21%) respondents admitted patients for treatment and delivered multiple fractions with a single insertion; four (29%) respondents treated patients as inpatients but used separate insertions for each fraction (Fig. 2). Five out of 14 respondents (36%) use four fractions for interstitial implants, whereas other common fractionation schemes were as follows: 5 (29%), 3 (21%), and 6 (7%). One of the respondents (7%) used single fraction pulsed dose rate for IBT.
0 As an in-patient, single As an in-patient, multiple insertion insertions
As an out-patient, multiple insertions
Fig. 2. Interstitial brachytherapy delivery across Canadian centers.
between 2012 and 2015. In 2012, 6 of 24 (25%) of centers did not contour any of the volumes (gross tumor volume, HR CTV, intermediate risk, bladder, rectum, or sigmoid colon) compared to just 1 of 28 (4%) centers in 2015 ( p 5 0.02). The proportion of centers that prescribed to HR CTV also increased from 12.5% (3/24) in 2012 to 50% (14/28) in 2015 ( p 5 0.004, Fig. 3). The proportion of centers that reported dose to the gross tumor volume, HR CTV, or both also increased from 83% in 2012 to 96% in 2015 ( p 5 0.12). There were a variety of dose and fractionation schedules used for cervical cancer BT in 2015. These are summarized in Table 2. The most common dose and fractionation regimen for both early and advanced stage cervical cancer was 6 Gy 5 fractions.
Discussion BT is the most effective way to deliver a high dose of conformal radiation therapy and is recommended for all cases of localized cervical cancer after external beam radiation. The objective of the current survey was to document patterns of care for cervical cancer BT in Canadian cancer centers in 2015 and assess changes in practice compared to 1 Proportion of responding centers
Number of Canadian centers in 2015 using IBT (n 5 14) Number of centers that did not use IBT but referred patients to another center for IBT (n 5 10 out 14) Selection of patients for IBT (n 5 14) Based on disease extent/imaging at the time of diagnosis Based on disease extent/imaging before BT Based on disease extent/imaging at the time of BT Based on disease extent/imaging at diagnosis and before BT Based on disease extent/imaging before BT and at the time of BT Based on all three criteria IBT technique available at responding centers (n 5 14) Hybrid applicator (Vienna or Utrecht type) only Hybrid applicator or free-hand template-based needle insertion Free-hand template-based only Guidance used for needle placement (n 5 14)a Strategy based on pre-op imaging alone Intra-op ultrasound Intra-op MR Intra-op CT
(2016)
0.6
Table 1 Interstitial brachytherapy (IBT) practice across Canada IBT Practice Details
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0.9
2012 (N=24)
0.8
2015 (N=28)
0.7 0.6
*
0.5 0.4 0.3 0.2 0.1 0
Volumes, dose, and fractionation Across Canada, there was a notable increase in the proportion of centers that performed volume-based BT
HR CTV
HR CTV, but using Point A as a reference
Point A
Fig. 3. Dose prescription practices across various centers in Canada. *p 5 0.004, chi-square. HR CTV 5 high-risk clinical target volume.
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Table 2 Dose and fractionation for cervix cancer HDR brachytherapy in Canada in 2015 Dose and fractionation by stage category Early stage (IBeIIA)a 6 Gy 5 8 Gy 3 7 Gy 4 5.5 Gy 5 6.5 Gy 5 5 Gy 5 6.75 Gy 4 PDR Advanced stage (IIBeIII)b 6 Gy 5 8 Gy 3 7 Gy 4 5.5 Gy 5 7.5 Gy 3 PDR
Crude total dose (Gy)
Total dose (2 Gy Eq, a/b 5 10)
% Respondents
30 24 28 27.5 26 25 27 35
40.0 36.0 39.7 35.5 35.8 31.3 37.7 35.0
37 19 15 11 7 4 4 4
30 24 28 27.5 22.5 40e45
40.0 36.0 39.7 35.5 32.8 40e45
52 19 15 7 4 4
PDR 5 pulsed dose rate; HDR 5 high dose rate; EBRT 5 external beam radiotherapy. a 96% of respondents combine above HDR regimen with 45 Gy/25 fractions EBRT and 4% combine it with 46 Gy/23 fractions. b 52% of respondents combine above HDR regimens with 45 Gy/25 fractions EBRT, 22% combine with 50.4 Gy/28 fractions, 15% combine it with range of 45e50 Gy/25 fractions, and 11% combine it with 50 Gy/25 fractions.
prior surveys conducted in 2012. Prior surveys documented the shift from low-dose-rate to HDR BT and the transition from two-dimensional to 3D planning and treatment delivery within Canadian centers (5, 6). The current survey added questions to assess the use of IBT practice across Canada. This survey affirms that a majority of the responding centers use HDR BT. At the time of this survey, 3D image guidance has become standard for BT within Canadian centers as 27 out of 28 respondents reported using either CT, MRI, or a combination of both CT and MRI for applicator insertion, treatment planning, and delivery. Many studies have reported an improvement in dosimetry and clinical outcomes with MRI-based treatment planning (13, 15, 16). Only 1 out of 28 centers continue to use orthogonal x-rays as the primary modality for BT. This finding is similar to that observed in the United States by Grover et al. (7). We postulate that this overall shift may translate into an improvement in cervical cancer outcomes on a national basis in Canada. An increase in availability of in-suite imaging was observed in the current survey compared to the 2012 survey. There is an increase in the number of centers in the United States and worldwide that have adopted in-suite imaging techniques, such as US, cone-beam CT, CT on rails and MRI to assist with applicator insertion, interstitial needle placement, volume delineation, and treatment planning (9, 17, 18). This is also reflected in the ABS practice pattern
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survey conducted in 2014 (7). Precision in applicator and needle placement not only improves clinical outcomes, but also decreases the rate of acute complications (19). IBT is crucial for providing adequate dose to large tumors that cannot be encompassed with standard intracavitary applicators to ensure good clinical outcome (20e29) while keeping the dose to normal organs low (30). No previous data are available on implementation and utilization of IBT in Canada. Patterns of care analyses have shown a decline in the use of IBT in the United States (31). These studies were performed before the widespread commercial availability of hybrid interstitial applicators. It is likely that the availability of these applicators combined with increased use of 3D image-guided planning will reverse this trend. This survey shows that, in Canada, hybrid applicators are being increasingly used (5/28 centers), and there remains a strong tradition in the use of interstitial templatebased BT as well (11/28 centers). These techniques are complementary. Hybrid applicators can typically extend the HR CTV coverage by up to 1 cm laterally without compromising organs at risk dose compared to standard intracavitary applicators (24). Where extensive lateral or vaginal disease remains after external beam radiation, interstitial template-based treatment is preferred. MRI guidance is essential in performing IBT, as described by GECESTRO and ABS guidelines (3, 32). This survey confirms that in Canada, centers that have improved access to MRI planning (using either in-suite or the local diagnostic imaging department) are performing IBT. Improvement in BT techniques and increased availability of image guidance as well as interstitial techniques have renewed interest in BT. One, however, must be cautious in recommending BT to be universally available at all centers treating gynecologic cancer, especially IBT. Compton et al. (33) published a survey of Accreditation Council for Graduation Medical Education recognized radiation oncology programs in the United States in 2013 and reported a significant decline in the resident experience with IBT. A 2015 Canadian national survey of practicing radiation oncologists, residents, and fellows concluded that there is a need for development of BT-specific curriculum and a credentialing process (34). That survey asked residents and fellows about their satisfaction regarding training in cervical cancer intracavitary BT and IBT; 70% respondents were satisfied with intracavitary BT teaching, whereas less than 10% felt satisfied with IBT teaching/training. More than 90% of respondents were either dissatisfied or neutral in regards to IBT teaching, and more than 70% of respondents had no competency or exposure to IBT for cervix cancer. Ultimately, this deficiency in training and exposure results in lack of confidence in offering or performing BT by the radiation oncologists after they finish training. The current survey found that 50% of the Canadian centers performing BT for patients with cervical cancer provided IBT and most of those centers were directly affiliated with academic institutions. This may be an
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appropriate balance in Canada at this time, with additional centers introducing IBT program in the coming years as they develop expertise and resources to perform these procedures. A multidisciplinary team including radiation oncologists, medical physicists and dosimetrists with specialty training in BT, gynecology oncologists, body radiologists, MRI treatment planning capability and appropriate operating room, in-patient, and nursing support services are essential in order for a center to effectively perform IBT procedures. Limitations This is a retrospective audit of BT practices within Canadian centers. Nonetheless, it provides important information that can help guide future national/international guidelines and clinical trials. Furthermore, the response rate, though excellent, was not complete. Conclusions In Canada, treatment of cervical cancer continues to evolve. IBT has been adopted by half of the responding centers. As more centers move to MRI-based image-guided treatment planning, IBT will become an even more integral part of cervical cancer treatment.
Acknowledgments The authors thank Dr. Marc Gaudet, Dr. Boris Bahoric, and the Canadian Brachytherapy Group for their assistance and support of this survey. References [1] 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. [2] Nag S, Cardenes H, Chang S, et al. Proposed guidelines for imagebased intracavitary brachytherapy for cervical carcinoma: Report from Image-Guided Brachytherapy Working Group. Int J Radiat Oncol Biol Phys 2004;60:1160e1172. [3] P€ otter R, Haie-Meder C, Van Limbergen E, et al. Recommendations from gynaecological (GYN) GEC ESTRO working group (II): Concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology. Radiother Oncol 2006;78:67e77. [4] Haie-Meder C, P€ otter R, Van Limbergen E, et al. Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): Concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005;74:235e245. [5] Phan T, Mula-Hussain L, Pavamani S, et al. The changing landscape of brachytherapy for cervical cancer: A Canadian practice survey. Curr Oncol 2015;22:356e360. [6] Pearce A, Craighead P, Kay I, et al. Brachytherapy for carcinoma of the cervix: A Canadian survey of practice patterns in a changing era. Radiother Oncol 2009;91:194e196.
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[26] Beriwal S, Kannan N, Kim H, et al. Three-dimensional high dose rate intracavitary image-guided brachytherapy for the treatment of cervical cancer using a hybrid magnetic resonance imaging/computed tomography approach: Feasibility and early results. Clin Oncol (R Coll Radiol) 2011;23:685e690. [27] Nomden CN, de Leeuw AA, Roesink JM, et al. Clinical outcome and dosimetric parameters of chemo-radiation including MRI guided adaptive brachytherapy with tandem-ovoid applicators for cervical cancer patients: A single institution experience. Radiother Oncol 2013;107:69e74. [28] Yoshida K, Yamazaki H, Takenaka T, et al. Preliminary results of MRI-assisted high-dose-rate interstitial brachytherapy for uterine cervical cancer. Brachytherapy 2015;14:1e8. [29] Mesko S, Swamy U, Park S-JJ, et al. Early clinical outcomes of ultrasound-guided CT-planned high-dose-rate interstitial brachytherapy for primary locally advanced cervical cancer. Brachytherapy 2015;14:626e632.
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[30] Bansal AK, Semwal MK, Sharma DN, et al. A patient-based dosimetric study of intracavitary and interstitial brachytherapy in advanced stage carcinoma of the cervix. J Appl Clin Med Phys 2014;15:4509. [31] Eifel P, Ho A, Khalid N, et al. Patterns of radiation therapy practice for patients treated for intact cervical Cancer in 2005 to 2007: A quality research in radiation oncology study. Int J Radiat Oncol Biol Phys 2014;89:249e256. [32] Lee L, Das I, Higgins S, et al. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part III: Low-dose-rate and pulsed-dose-rate brachytherapy. Brachytherapy 2012;11:53e57. [33] Compton JJ, Gaspar LE, Shrieve DC, et al. Resident-reported brachytherapy experience in ACGME-accredited radiation oncology training programs. Brachytherapy 2013;12:622e627. [34] Gaudet M, Jaswal J, Keyes M. Current state of brachytherapy teaching in Canada: A national survey of radiation oncologists, residents, and fellows. Brachytherapy 2015;14:197e201.