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Journal of Contemporary Brachytherapy
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Original paper

High-dose-rate interstitial brachytherapy for accelerated partial breast irradiation – trial results of Azerbaijan National Center of Oncology

Jamil A. Aliyev, Isa H. Isayev, Kamal S. Akbarov, Samir S. Qurbanov, Ruslan R. Huseynov, Nigar S. Aliyeva

J Contemp Brachytherapy 2017; 9, 2: 106–111
Online publish date: 2017/04/13
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Purpose

Recently, partial breast irradiation has become a standard adjuvant treatment modality for early stage breast cancer [1,2,3,4,5,6,7]. It could be done by different radiotherapy techniques like photon beams, electron beams, and brachytherapy [7,8,9,10,11,12]. In our view, accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy (BT) has the major advantages like more conformal and flexible dose distribution pattern, limitation of very high dose (particularly close around to applicators) in small volume (i.e., tumor bed), excellent protection of organs at risk (heart, skin, lung), advantageous cosmetic results, and very short treatment time [2,13,14,15]. In case of use of external beam radiotherapy (EBRT), some of above mentioned issues also could be overcome, but only due to rather complicated treatment techniques: respiratory gating (i.e., deep inspiration breath hold), breast immobilization, treatment in prone position etc., while others could not, even by implementation of the latest EBRT achievements [16,17,18]. Therefore, today interstitial multicatheter brachytherapy based APBI is probably the most appropriate method corresponding to requirements for partial breast radiotherapy [2,19,20,21].
There is a number of publications available about high-dose-rate interstitial APBI, but in the majority of them, different dose fractionation was used: from 10 to 7 fractions by 3.4 Gy to 5.2 Gy [19,21,22,23,24]. We started APBI as treatment option for early breast cancer in 2012, after institutional review board approved treatment protocol. The primary objective of presented trial was to compare early results of patients received APBI with different schedules of multicatheter brachytherapy.

Material and methods

Eligibility

We analyzed treatment results of 48 patients with early stage breast cancer who received adjuvant multicatheter interstitial APBI after breast conserving surgery at the National Center of Oncology, Baku from January 2012 to December 2014. Inclusion criteria, according to the Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO) recommendations on patient selection for APBI of low and intermediate risk groups were as follows: age ≥ 40 years, tumor size by final pathology ≤ 3 cm, negative axillary lymph nodes (sentinel or dissection), microscopically negative or close (≤ 2 mm) surgical margins, invasive ductal or lobular carcinoma, unicentric/unifocal tumors. Exclusion criteria consisted of younger age, tumors more than 3 cm in size, positive margins (presence of tumor tissue on surgical margins), axillary lymph nodes’ metastasis, presence of extensive intraductal component, multicentric/multifocal tumors [24,25,26,27,28]. All patients have signed informed consent before the treatment. Patient and tumor characteristics are given in Table 1.

Brachytherapy technique

Implantations usually were done 3-5 weeks after breast conserving surgery under general anesthesia [29,30]. We used plastic tube applicators of specialized interstitial breast catheter kits (Varian Medical Systems, Inc., Palo Alto, CA, USA). At the beginning, to keep both parallel orientation and equal distance between inserted needles, an advanced breast template system applicator (Varian Medical Systems, Inc., Palo Alto, CA, USA) was applied. Since 2015, we have practiced free hand needle insertion technique.
Tumor bed was defined based on pre-surgery mammograms, ultrasonography (US), and magnetic resonance imaging (MRI) investigations, and pre-implantation 2 mm slice thickness computed tomography (CT)scan without contrasting, which allowed visualization of scar, seroma, fibrosis area, clips, and projection of these structures on the skin. Additionally, the relation of needles to the clips was checked by X-rays (C-arm) during implantation procedure.
Needles were introduced in triangular setting with 15 mm distance, in amount sufficient enough to cover previously defined tumor bed with 1.5-2.0 cm margin. Seven to eighteen (median, 11) plastic catheters were used for adequate covering of the clinical target volume (CTV). The high-dose-rate brachytherapy (HDR-BT) was applied on an out-patient basis, two times daily with 4 to 6 hours interval. Twenty one patients received 8 fractions by 4 Gy (arm one), and 27 – 7 fractions by 5 Gy HDR-BT (arm two). Total treatment time including the day of implantation was four and five days, respectively. For skin care and infection prophylaxis, we used an aseptic bandages with povidoneiodine or octenidine applied to the areas of applicators enter-exit. Patients were advised against taking a shower for the duration of treatment. Routine administration of antibiotics was not done. Immediately after the last fraction, catheters were removed and patients were discharged.

Planning and treatment

High-dose-rate brachytherapy was done using 192Ir source of 370 GBq initial activity with GammaMed HDR Plus afterloading machine (Varian Medical Systems, Inc., Palo Alto, CA, USA). Target definition and delineation was done according GEC-ESTRO Breast Cancer Working Group recommendations [26]. Post implantation CT images were transferred to BrachyVision treatment planning system (Varian Medical Systems, Inc., Palo Alto, CA, USA), on which the target volume segmentation and planning was performed. After the tumor bed was identified, a margin of 1.5 cm was uniformly expanded while keeping a minimum distance of 5 mm from the skin surface to create a CTV. Posteriorly, the CTV did not expand to the chest wall muscles. Planning target volume (PTV) was the same as CTV. After catheters’ reconstruction, a geometrical optimization with subsequent manual modification of the dwell times and positions was done to achieve homogenous dose distribution among the CTV. The aimed dose constraints for the plan were: V100 for CTV > 90%, dose non-homogeneity ratio (DNR, relation of volume received 150% of prescribed dose to the volume received 100% of prescribed dose, V150/V100%) was ≤ 0,33, and the dose to the skin surface and chest wall ≤ 70% of prescribed dose. Twenty two patients received 8 times 4 Gy, and twenty six patients 7 times 5 Gy fractions.

Adjuvant systemic therapy

Adjuvant chemotherapy and endocrine therapy were done after APBI according to National Comprehensive Cancer Network (NCCN) guidelines: 29 (60.4%) patients received chemotherapy, and 41 (85.4%), endocrine therapy (see Table 2) [31].

Results

The mean DNR was 0.35 (SD: 0.05; range, 0.29-0.45). The mean for maximum skin surface dose per fraction was 2.1 Gy (range 1.8-3 Gy) in 8 fraction, and 2.6 Gy (range 2.1-3.7 Gy) in 7 fraction brachytherapy regimens. There were no significant differences in the main treatment indexes between two arms (Table 3). Analysis of dose distribution within the CTV by use of different partial breast irradiation techniques shows different pattern of dose delivery. Thus, the total dose of EBRT to tumor bed is 50-60 Gy (both for early and late effects), given by 2 Gy fractions, while the total dose of APBI in our study is 37.3 Gy and 44.8 Gy in arm one (8 APBI fraction), and 43.8 Gy and 56.0 Gy in arm two (7 APBI fraction) for early (/ = 10 Gy) and late (/ = 3 Gy) effects, respectively. As it can be seen from the above calculations, the tumor dose of APBI is significantly less than one’s of EBRT (37.3 Gy and 43.8 Gy dose equivalent to 2 Gy fractionation [EQD2] vs. 50-60 Gy). But these doses are the minimum doses at the periphery of CTV, and we should take into consideration that the dose distribution of interstitial APBI is highly non-homogenous in comparison with EBRT. The mean volume of CTV in our patients was 101.7 cc, while mean V150% was 37.8 cc. Therefore averagely, 37.2% of CTV (highest risk CTV, according to needle placement within the tumor bed) received 64 Gy (arm one) and 76.6 Gy (arm two), and higher EQD2 dose. On the other hand, APBI by multicatheter interstitial brachytherapy allows significant decrease of radiation exposure of organs at risk in comparison to whole breast EBRT three to four fold [32,33,35].
All patients were followed-up every three months during the first two years after treatment, and then every six month. Examination included mammography, ultrasound of breast and regional lymph nodes bilaterally, abdomen and pelvis, chest X-rays, blood test, echocardiography, gynecological examination. Mammograms were obtained every 12 months, or if any suspicion arise. In case of abnormal findings during mammography and ultrasound analysis, additional breast MRI and, if necessary, core-needle biopsy were performed to exclude local recurrence. The median follow-up was 37 months for all patients, 41 months for eight fractions APBI patients (arm one), and 33 months for seven fractions APBI patients (arm two). No loco-regional nor distant relapses were found during this period.
Cosmetic effects were evaluated using four grade score as excellent, good, moderate, and poor, according to Harvard criteria of Harris et al. E0: excellent aesthetic result, at first sight no visible therapy related sequalae, both breasts have a similar appearance; E1: good, minimal changes in pigmentation, a visible scar, localized telangiectasia; E2: moderate, marked sequalae with a clear deformation of the breast contour, nipple displacement, or marked skin changes, but yet “acceptable”; E3: bad, severe retraction or fibrosis, severe telangiectasia; E4: complications: skin necrosis [32,33]. Fat necrosis was evaluated according to Lovey et al. scoring system: grade 0 – no fat necrosis; grade 1 − asymptomatic fat necrosis (painless palpable mass, radiologic or cytological findings); grade 2 − symptomatic fat necrosis requiring non-narcotic analgesics; grade 3 − symptomatic fat necrosis requiring narcotic analgesics for more than 2 weeks; grade 4 − symptomatic fat necrosis requiring surgical intervention [33,34]. There were no significant differences according to cosmetic results between two arms of patients. Cosmetic results were excellent in 13 (27.1%) patients, good – in 34 (70.8%) patients, moderate in one patient (2.1%). Forty-three (89.6%) of 48 patients were free of fat necrosis during follow-up period. In total, five patients developed fat necrosis, of which four (8.3%) had grade 1 fat necrosis revealed as painless mass by palpation and proven by mammography. Only one patient developed grade 2 symptomatic fat necrosis with painful palpable breast mass requiring core-needle biopsy. She was treated by two week course of analgesic and steroid with good cosmetic result.

Discussion

There are several dose/fractionation regimens of interstitial multicatheter APBI have been reported in literature: from 10 times 3.4 Gy to 7 times 5.2 Gy [22]. Polgar et al. found although non-significant trend for higher local recurrence rate for those patients treated with a lower tumor bed dose (10-year local relapse rate with 30.3 and 36.4 Gy tumor bed dose: 28.6% vs. 5.6%; p = 0.073) [21]. In our study, we compared late side effects of two different APBI regimens after median follow-up of 3 years and did not find any significant differences between them. The rationale to change fractionation schedule were both logistical reasons and patients’ compliance. Lesser amount of radiotherapy fractions is more convenient for patients, particularly for those who travel for a long distance from radiotherapy center. Also, earlier removing of interstitial catheters could lead to decrease of secondary infection probability. On the other hand, shorter treatment time is more usable for department staff: less load of medical personnel (less treatment procedures, dressings etc.) and brachytherapy devices.
Increase of fraction size did not lead to higher probability of fat necrosis in our observation, but we still need longer follow-up for final conclusion. Thus, Budrukkar et al. investigating fat necrosis at 171 patients after interstitial APBI for early stage breast cancer with median follow up time 48 months revealed that median time to develop of a event was 24 months (range, 4-62 months; SD, 20), and the only significant factor impacting adversely on fat necrosis probability was volume of surgical excision [34]. In another study, Lövey et al. [36] found increased dependence of fat necrosis incidence from V150% of more than 70 cc and V200% of 20 cc, which could be avoided due to proper needle placement and dose optimization by 3D CT based planning (in our patients mean V150% was 37.8 cc and mean V200% was 10.4 cc). Therefore, according to recent data, there is no evidence of connection between the most frequent late complication as fat necrosis and APBI fraction size.

Conclusions

After 3 years follow-up, we did not find any differences between 32 Gy/8 fractions and 35 Gy/7 fractions APBI regimens in terms of disease free survival and early and late toxicity of the treatment. According to our findings, APBI was also feasible for intermediate-risk early breast cancer patients. Further researches with inclusion of low and intermediate risk group patients could substantiate new, shorter, and equally effective APBI regimens, which would be more convenient for patients, especially for those who travel long distances (taking into consideration that APBI technique is mostly available in dedicated radiotherapy centers). Shorter (2-3 days) APBI regimens also could improve radiotherapy workflow.

Acknowledgments

The authors would like to thank Prof. Vratislav Strnad, Head of Division Interventional Radiation Oncology, University Hospital Erlangen, Germany for his contribution.

Disclosure

Authors reports no conflict of interest.

References

1. Polgar C, Fodor J, Major T et al. Breast-conserving therapy with partial or whole breast irradiation: ten-year results of the Budapest randomized trial. Radiother Oncol 2013; 108: 197-202.
2. Strnad V, Ott OJ, Hildebrandt G et al.; Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomized, phase 3, non-inferiority trial. Lancet 2016; 387: 229-238.
3. Antonucci J, Wallace M, Goldstein N et al. Differences in patterns of failure in patients treated with accelerated partial breast irradiation versus whole breast irradiation: a matched-pair analysis with 10-year follow-up. Int J Radiat Oncol Biol Phys 2009; 74: 447-452.
4. Johansson B, Karlsson L, Liljegren G et al. Pulsed dose rate brachytherapy as the sole adjuvant radiotherapy after breast-conserving surgery of T1-T2 breast cancer: first long time results from a clinical study. Radiother Oncol 2009; 90: 30-35.
5. Polgar C, Strnad V, Major T. Brachytherapy for partial breast irradiation: the European experience. Semin Radiat Oncol 2005; 15: 116-122.
6. Polgar C, Major T, Fodor J et al. High-dose-rate brachytherapy alone versus whole breast radiotherapy with or without tumor bed boost after breast conserving surgery: seven-year results of a comparative study. Int J Radiat Oncol Biol Phys 2004; 60: 1173-1181.
7. Marta G, Macedo C, de Andrade Carvalho H et al. Accelerated partial irradiation for breast cancer: Systematic review and meta-analysis of 8653 women in eight randomized trials. Radiother Oncol 2015; 114: 42-49.
8. Vaidya J, Wenz F, Bulsara M et al. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomized trial. Lancet 2014; 383: 603-613.
9. Veronesi U, Orecchia R, Maisonneuve P et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomized controlled equivalence trial. Lancet Oncol 2013; 14: 1269-1277.
10. Vicini F, Winter K, Wong J et al. Initial efficacy results of RTOG 0319: three-dimensional conformal radiation therapy (3D-CRT) confined to the region of the lumpectomy cavity for stage I/II breast carcinoma. Int J Radiat Oncol Biol Phys 2010; 77: 1120-1127.
11. Kuske R, Winter K, Arthur D et al. Phase II trial of brachytherapy alone after lumpectomy for select breast cancer: toxicity analysis of RTOG 95-17. Int J Radiat Oncol Biol Phys 2006; 65: 45-51.
12. Strnad V, Hildebrandt G, Pötter R et al. Accelerated partial breast irradiation: 5-year results of the German-Austrian multicenter phase II trial using interstitial multicatheter brachytherapy alone after breast-conserving surgery. Int J Radiat Oncol Biol Phys 2011; 80: 17-24.
13. Bitter S, Heffron-Cartwright P, Wennerstrom C et al. WBRT vs. APBI: an interim report of patient satisfaction and outcomes. J Contemp Brachytherapy 2016; 8, 1: 17-22.
14. Vargo J, Verma V, Kim H et al. Extended (5-year) outcomes of accelerated partial breast irradiation using MammoSite balloon brachytherapy: patterns of failure, patient selection, and dosimetric correlates for late toxicity. Int J Radiat Oncol Biol Phys 2014; 88: 285-291.
15. Wazer D, Kaufman S, Cuttino L et al. Accelerated partial breast irradiation: an analysis of variables associated with late toxicity and long-term cosmetic outcome after high-dose-rate interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2006; 64: 489-495.
16. Shah C, Antonucci J, Wilkinson J et al. Twelve-year clinical outcomes and patterns of failure with accelerated partial breast irradiation versus whole-breast irradiation: results of a matched-pair analysis. Radiother Oncol 2011; 100: 210-214.
17. Latty D, Stuart K, Wang W, et al. Review of deep inspiration breath-hold techniques for the treatment of breast cancer. J Med Radiat Sci 2015; 62: 74-81.
18. Harat A, Harat M, Makarewicz R. Whole breast irradiation vs. APBI using multicatheter brachytherapy in early breast cancer – simulation of treatment costs based on phase 3 trial data. J Contemp Brachytherapy 2016; 8: 505-511.
19. Lyons J, Woods C, Galanopoulos N et al. Emerging Radiation Techniques for Early-stage Breast Cancer After Breast-conserving Surgery. Future Oncol 2011; 7: 915-925.
20. Lakosi F, Gulyban A, Simoni S et al. The influence of treatment position (prone vs. supine) on clip displacement, seroma, tumor bed and partial breast target volumes: comparative study. Pathol Oncol Res 2016; 22: 493-500.
21. Polgar C, Major T, Fodor J et al. Accelerated partial-breast irradiation using high-dose-rate interstitial brachytherapy: 12-year update of a prospective clinical study. Radiother Oncol 2010; 94: 274-279.
22. Budrukkar A, Gurram L, Upreti R et al. Clinical outcomes of prospectively treated 140 women with early stage breast cancer using accelerated partial breast irradiation with 3 dimensional computerized tomography based brachytherapy. Radiother Oncol 2015; 115: 349-354.
23. Offersen B, Overgaard M, Kroman N et al. Accelerated partial breast irradiation as part of breast conserving therapy of early breast carcinoma: A systematic review. Radiother Oncol 2009; 90: 1-13.
24. Aristei C, Palumbo I, Capezzali G et al. Outcome of a phase II prospective study on partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy. Radiother Oncol 2013; 108: 236-241.
25. Hattangadi J, Powell S, MacDonald S et al. Accelerated partial breast irradiation with low-dose-rate interstitial implant brachytherapy after wide local excision: 12-year outcomes from a prospective trial. Int J Radiat Oncol Biol Phys 2012; 83: 791-800.
26. Strnad V, Hannoun-Levi J, Guinot J et al. Recommendations from GEC ESTRO Breast Cancer Working Group (I): Target definition and target delineation for accelerated or boost Partial Breast Irradiation using multicatheter interstitial brachytherapy after breast conserving closed cavity surgery. Radiother Oncol 2015; 115: 342-348.
27. Polgar C, Van Limbergen E, Pötter R et al.; GEC-ESTRO breast cancer working group. Patient selection for accelerated partial-breast irradiation (APBI) after breast-conserving surgery: Recommendations of the GroupeEuropéen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) breast cancer working group based on clinical evidence (2009). Radiother Oncol 2010; 94: 264-273.
28. Gurram L, Wadasadawala T, Joshi K et al. Multi-catheter interstitial brachytherapy for partial breast irradiation: an audit of implant quality based on dosimetric evaluation comparing intra-operative versus post-operative placement. J Contemp Brachytherapy 2016; 8, 2: 116-121.
29. Shah C, Wobb J, Manyam B et al. Accelerated partial breast irradiation utilizing brachytherapy: patient selection and workflow. J Contemp Brachytherapy 2016; 8: 90-94.
30. Akhtari M, Abboud M, Szeja S et al. Clinical outcomes, toxicity, and cosmesis in breast cancer patients with close skin spacing treated with accelerated partial breast irradiation (APBI) using multi-lumen/catheter applicators. J Contemp Brachytherapy 2016; 86: 497-504.
31. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, Breast Cancer. Available at: https://www.nccn.org.
32. Van Limbergen E, Van der Schueren E, Van Tongelen K. Cosmetic evaluation of breast conserving treatment for mammary cancer. 1. Proposal of a quantitative scoring system. Radiother Oncol 1989; 16: 159-167.
33. Garsa AA, Ferraro DJ, De Wees T et al. Analysis of Fat Necrosis Following Adjuvant High-Dose-Rate Interstitial Brachytherapy for Early-Stage Breast Cancer. Brachytherapy 2013; 12: 99-106.
34. Budrukkar A, Jagtap V, Kembhavi S et al. Fat necrosis in women with early-stage breast cancer treated with accelerated partial breast irradiation (APBI) using interstitial brachytherapy. Radiother Oncol 2012; 103: 161-165.
35. Lettmaier S, Kreppner S, Lotter M et al. Radiation exposure of the heart, lung and skin by radiation therapy for breast cancer: A dosimetric comparison between partial breast irradiation using multicatheter brachytherapy and whole breast teletherapy. Radiother Oncol 2011; 100: 189-194.
36. Lövey K, Fodor J, Major T et al. Fat necrosis after partial-breast irradiation with brachytherapy or electron irradiation versus standard whole-breast radiotherapy-4-year results of a randomized trial. Int J Radiat Oncol Biol Phys 2007; 69: 724-731.
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