Accelerated partial breast irradiation


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APBI selection criteria,methods,results

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  • There is no data available that demonstrate that radiation therapy needs to be delivered to the whole breast. The only contemporary studies available applied extensive microscopic evaluation of both mastectomy and quadrantectomy specimens and all three of these studies focused on the distance of DCIS beyond the primary lesion. One looked at DCIS extension beyond the primary IDC and one study from primary DCIS lesions. All presented evidence suggesting that the extension of malignant cells is limited to less than 1cm from the primary lesions, except for younger patients.

    For correct delivery of a boost, precise demarcation of the excision cavity is mandatory; it has been estimated that the externally delivered boost misses the target volume in 24-88% of cases.

  • At 5 years, APBI patients continued to experience a higher proportion of adverse cosmesis (32.8% v 13.4%; absolute difference, 19.4%; 95%
    CI, 10.4 to 27.9; P.001).
  • Accelerated partial breast irradiation

    2. 2. OUTLINE 1. Rationale 2. Selection criteria 3.Techniques  Brachytherapy  EXRT  IORT  Novel methods 4. Technological aspects
    3. 3. 5.Review of literature  Outcomes and patterns of failure  Toxicities and challenges  Comparison of different techniques 6. Ongoing trials 7. Pre-op APBI !!!!
    4. 4. Based on 6 RCT & meta-analyses it was shown that RT is an integral component of breast conservation therapy and is the std. of care in early breast cancer BUT 15% to 30% of patients who undergo lumpectomy do not receive radiation therapy Hershman Dlet al. J Natl Cancer Inst 2008;100:199–206. Pawlik Tmet al. J Am Coll Surg 2004;199:479–92.
    5. 5. WHY…  Commitment to the 6- 7 week course of adjuvant conventional RT  Cost  Distance from the radiation therapy facility  Lack of transportation  Lack of social support structure  Poor ambulatory status of the patient  Physician bias  Patient age  Fear of radiation treatment
    6. 6. SO THE QUESTION ARISES THAT ‘ can similar rates of local control be achieved with radiation therapy delivered only to the area at highest risk for recurrence?’If so, radiation could be delivered in a significantly shortened period
    7. 7. RATIONALE
    8. 8. 8 Veronesi U, et al. NEJM 2002;347:1227–32 Majority of local recurrences (LRs) occur in proximity to the tumour bed  Less than 20% of LRs appear ‘‘elsewhere” in the breast the absolute number of such failures is very low. < 1% per yr . & similar to the recurrence of contra-lateral second primary breast cancer.
    10. 10. WHY GUIDELINES  30,000 pts have been treated outside the clinical trial in past few years despite encouraged use of APBI in clinical trial only.  Ongoing RCT will be published in next 3-5 yrs.  Give recommendations on patient selection criteria for the use of APBI outside the context of prospective clinical trials
    11. 11. CLINICAL RESULTS OF APBI USING SUBOPTIMAL PATIENT SELECTION Results were poor, with high LR rates exceeding 1% per year Polgar et al,Radiotherapy and Oncology 94 (2010) 264–273
    12. 12. OPTIMAL SELECTION All invasive carcinomas + DCIS ER negative tumors also included Shah et al. Brachytherapy 12(2013) 267-77
    13. 13. TECHNIQUES OF APBI  Interstitial Brachytherapy  Intracavitory Brachytherapy  EXRT  IORT  Permanent seeds  Accu boost
    15. 15. METHOD Open procedure  Direct visualization of the lumpectomy cavity/clips  Free hand method  After catheter placement , wound closure and position secured
    16. 16. Closed cavity implant After the final pathology information to guide appropriate patient selection. Local anaesthesia given 15-30 min before the implantation. Virtual planning Simulator /CT based  Appropriate number of catheters  Number of catheter planes  Optimal direction of placement.
    17. 17. Target volume  Lumpectomy cavity plus a 2-cm margin  Near chest wall and skin -1 to 1.5 cm Dose  HDR-34 Gy/10# bid in 5 days  LDR- 45 Gy @ 50 cGy/hr over 4.5 days Arthur et al. IJROBP 2003 vol 56, 681-9
    18. 18. Catheters implantation  Free hand technique  Template to ensure even needle spacing Under image guidance using  Ultrasound  Fluoroscopy  CT  Combination of modalities
    19. 19. DESIGN OF THE IMPLANT GEOMETRY  Needles are implanted parallel and equidistance from each other (Paris system).  In most cases inserted in a mediolateral direction.  In very medially or laterally located tumor sites, needles should be implanted in a craniocaudal direction to enable separate target area from skin points.  In some rare cases, the upper outer quadrant has to be implanted with needles orientated in a 45° angle to avoid overlap of source positions and skin
    20. 20.  2 planes of needles are usually needed to cover the PTV.  Single plane< 12 mm.  Three planes are required in a large breast where the targeted breast tissue between pectoral fascia and skin is thicker than 30 mm.  Five to nine needles spaced 15–20 mm are usually required.
    21. 21. REDUCTION IN SKIN DOSE Skin to source measuring bridge is used.  If the superficial needles are too close to the skin, the templates are moved towards each other so that the overlying skin moves up and away from the needles.  If this is not sufficient, templates with a smaller spacing between the needles are used, resulting in compression of the breast tissue and upward movement of the skin  Some gauze is disposed between the templates and the skin of the thoracic wall at both sides of the implant to avoid skin necrosis secondary to continuous pressure of templates.
    22. 22. ADVANTAGES  Longest follow-up.  Better control and tailoring of radiation-dose delivery to variations in lumpectomy cavity, shape, or location within the breast.  Limits toxicity to healthy tissue while delivering the maximum dose to at-risk tissue.  Critical structures can be avoided by differential loading of the catheters
    23. 23. LIMITATIONS  Considerable training and experience  Appearance and patient acceptance of multiple catheter implants in the breast  high skin dose: great care is required to ensure adequate source-to-skin distance in patients treated with brachytherapy Therefore, may not be a viable treatment option for patients with superficial tumors or small breasts
    24. 24. RESULTS Njeh et al. Radiation Oncology 2010, 5:90
    25. 25.  n=258  pT1 pN0 grade 1–2,  Age>40 WBI 130 PBI 7.2 Gy in 5 #
    26. 26. ONGOING TRIAL (INTERSTITIAL BT) GEC- ESTRO n=1233 WBI (50 Gy/ 25#) +/- boost Interstitial brachytherapy 32 Gy in 8 fractions HDR, 30 Gy in 7 fractions HDR, 50 Gy PDR >40 years, Stages 0-II (T 3 cm), DCIS or invasive adenocarcinoma Node negative or with micro- metastasis Margin 2 mm Accrual completed, Results awaited
    28. 28. Balloon based brachytherapy include:  Mammosite  Axxent electronic brachytherapy  Contura
    30. 30. STRUCTURE  Silicone balloon  Double-lumen catheter (15 cm length and 6 mm in diameter)  Inflation channel:- saline solution mixed with a small amount of contrast material to aid visualization.  Source channel:- for passage of an Ir-192 high dose rate (HDR) brachytherapy source.  Source channel runs centrally through the length of the balloon.
    31. 31.  after lumpectomy, the catheter is placed in the breast cavity either during the lumpectomy procedure or later through a closed technique  balloon is inflated with 35 to 70 mL of saline mixed with a small amount of contrast material, depending on the size of the lumpectomy cavity  CT imaging to assess the adequate placement of the device  An Ir-192 radioactive source, connected to a computer-controlled HDR remote after-loader, is inserted through the catheter into the balloon to deliver the prescription radiation dose
    32. 32. QUALITY OF THE IMPLANT  Ballon Conformance: assessed by quantifying the volume of the PTV that is filled by air or seroma fluid.  Less than 10% of the PTV should be composed of fluid or air. Too much air Large seroma
    33. 33.  Minimum balloon-to-skin distance: for good cosmesis 5-7 mm is required Close to the skin
    34. 34.  Symmetry Essential for adequate dosimetry. A non-symmetrical implant can result in dose inhomogeneity in the surrounding tissues since the MSB device contains a single, central source channel that does not allow for shaping of the radiation isodose curves in the direction perpendicular to the central channel Asymmetrical
    35. 35. DOSE  34 Gy over 10 fractions (3.4 Gy per fraction, twice daily )  Prescription point is 1 cm from the balloon surface  Minimum 6 hours gap  D 90> 90%  V150< 50cc  V200< 20 cc  HI >0.75  Skin dose Max <145%
    36. 36. Limitations  Not suitable in patients with small breast .  Tumors located in the upper-inner quadrant.  Irregular cavity . (Requirement for skin-to-cavity distances:- not met) Advantages  More user-friendly technique for brachytherapy  Easily reproducible
    37. 37. MammoSite Multi-lumen (4 lumen) device
    38. 38. RESULTS OF MAMMOSITE Njeh et al. Radiation Oncology 2010, 5:90
    39. 39. Balloon based brachytherapy include:  Mammosite  Axxent electronic brachytherapy  Contura
    40. 40. AXXENT ELECTRONIC BRACHYTHERAPY Ballon is radiolucent :- No need of contrast Holes in the ballon Third port for drainage of seroma fluid or air surrounding the cavity.
    41. 41. Miniature X-ray source
    42. 42. eB controller •Portable unit •Digital touch-screen for the Physician and Physicist to input treatment data and monitor treatment progress.
    43. 43. ADVANTAGES  Specifically shielded radiation room or an HDR afterloader unit are not required.  This reduces costs and allows for portability of the system, which can lead to greater access for patients particularly in more remote or rural locations.  Can be used intraoperatively
    44. 44. CONTURA
    45. 45.  In addition to a central lumen, the Contura balloon has four surrounding channels to accommodate the HDR source.  Additional source positions allows increased dose flexibility compared with a single-catheter approach.  Vacuum port to remove fluid or air around the lumpectomy cavity.  Reduce the dose to normal tissues (chest wall and skin) better protection of organs at risk such as the heart and lungs.  Possible to account for asymmetric balloon implant with respect to the central channel.
    46. 46. HYBRID BRACHYTHERAPY DEVICES Struts Adjusted Volume Implant (SAVI)  ClearPath
    49. 49.  Consists of a central strut  Sorrounded by 6,8 or 10 peripheral struts  Can be differentially loaded with HDR source  Insertion done in collapsed form through an incision (LA ;USG guided)  Then expanded to fit the cavity  CT aquired (verification and planning)
    50. 50. CLEARPATH
    51. 51.  Contains six outer expandable plastic tubes to displace the tissue  Central catheter surrounded by six additional catheters that allow the passage of an HDR iridium-192 source  The radiation source is not in direct contact with the breast tissue
    53. 53. ADVANTAGES  Non-invasive (complications of surgery like seroma and infection can be avoided)  Widespread availability  Technically less demanding  Treatment results with external beam may be more uniform between radiation oncologists  Greater dose homogeneity
    54. 54. 3.85 Gy twice daily (separated by at least 6 hours) to a total dose of 38.5 Gy delivered within 1 week
    55. 55. RAPID TRIAL-RANDOMIZED TRIAL OF ACCELERATED PARTIAL BREAST IRRADIATION (2006) 2128 patients Hypofrationated WBI (42.5 Gy/ 16#/22 days) 38.5 Gy/10#/5-8 days APBI Large breasted patient :- 50 Gy/25# Boost allowed :- 10 Gy/5# (21%) Chemotherapy, if used, was completed before RT (15%)  >40 years, T < 3 cm, DCIS or invasive carcinoma, Node negative, Margin negative, No BRCA1 or 2
    56. 56. Patient Characteristics 8/4/2015 60
    57. 57. PLANNING  CTV – tumor bed on CT , including surgical clips plus 1 cm margin inside breast tissue  PTV- CTV + 1 cm margin  Prescribed dose 38.5 Gy in 10 # bid over 5-8 days/ minimum interfraction interval 6 hours  The breast volume planning goals  0% to receive>107%  <25% (up to 35% acceptable) to receive>95%,  <50% (up to 60% acceptable) to receive >50% of the prescription dose  Treated with 3-5 noncoplaner conformal fields 61
    58. 58. 8/4/2015 62
    59. 59. COSMETIC ANALYSIS By EORTC Cosmetic Rating System. At baseline, assessed by a trained nurse. Patient questionnaire Assessed by two panels of three radiation oncologists using the digital photographs on follow-up. The treated breast was compared with size and shape, location of the areola and nipple, appearance of the surgical scar, presence of telangiectasia, and global cosmetic score 63
    60. 60. COSMETIC OUTCOME 8/4/201564 Median follow-up- 36 months
    62. 62. NSABP B-39 TRIAL
    63. 63. EXRT (IMRT)
    64. 64. 5Y European Journal of Cancer (2015) 51, 451– 463  >40 years  T < 2.5cm  LVI not excluded  DCIS not excluded  ALN positive status not excluded 520 patients 2005-2013 n=1233 Conventional WBI (260) (50 Gy/ 25#/Boost 10 Gy ) APBI(260) 30 Gy/5# Nonconsecutive days 5year follow -up
    65. 65. No difference in local recurrence The APBI group presented significantly better results considering acute (p = 0.0001), late (p = 0.004), and cosmetic outcome (p = 0.045).
    67. 67. IORT
    68. 68. ADVANTAGES  Accurate dose delivery Direct visualization of the tumor bed  Better protection of healthy tissues by moving them away from the path of the radiation beam.  Eliminates the risk of geographical miss  Oxygen effect :-Rich vascularization in tissues with aerobic metabolism, which makes them more sensitive to the action of the radiation .  Single intraoperative application eliminates the risk of patients not completing the prescribed course of breast radiotherapy.  Does not require a specially designed operating room
    69. 69. TARGIT
    70. 70. Lancet 2010; 376: 91–102
    71. 71. P= 0.41(NS) N0 difference in local recurrence Radiotherapy toxicity was lower in the targeted intraoperative radiotherapy group (six patients [0·5%]) than in the external beam radiotherapy group (23 patients [2·1%]; p=0·002).
    72. 72. The 5-year risk for LR was 3·3% (95% CI 2·1– 5·1) for TARGIT versus 1·3% (0·7–2·5) for EBRT (p=0·042).
    73. 73. MOBETRON (ELECTRONS) • Control console which operates the accelerator during radiation treatment delivery • Modulator houses the electronic systems of the accelerator and energizes the accelerator to produce the electron • Therapy module houses the accelerator guide and control systems that generate and deliver radiation • 4 MeV, 6 MeV, 9 MeV and 12 MeV with therapeutic ranges up to 4 cm
    74. 74. NOVAC-7 (ELECTRONS) • Delivers electrons with the use of a mobile dedicated linear accelerator • Radiating head can be moved by an articulated arm that can work in an existing operating room • It delivers electron beams at four different nominal energies (3, 5, 7 and 9 Mev) • Beam are collimated by means of a hard docking system, consisting of cylindrical perspex applicators available in different diameters (4 to 10 cm) and angles of the head (perpendicular or oblique 15° to 45°)
    75. 75. Lancet Oncol 2013; 14: 1269–77 Age > 48- 75 yrs Tumor <2.5 cm 2000-2007  n=1305 N=654 50 Gy/25# plus boost N=651 IOERT 21 Gy single #
    76. 76. Follow-up= 5.8 years The 5-year event rate for IBRT was 4.4% in the IOERT group and 0.4% in the EXRT group.
    77. 77.  Significant difference in favor of WBI for different follow-up  times was also found. No differences in nodal recurrence, systemic recurrence, overall survival and  mortality rates were observed. Conclusions: APBI is associated with higher local recurrence compared  to WBI without compromising other clinical outcomes. Conclusions: APBI is associated with higher local recurrence compared to WBI without compromising other clinical outcomes. No differences in nodal recurrence, systemic recurrence, overall survival and mortality rates were observed
    78. 78. CURRENT STATUS
    79. 79.  Low risk - APBI outside the context of a clinical trial is an acceptable treatment option  High-risk group- APBI is considered C/I  Intermediate risk group- APBI is considered acceptable only in the context of prospective clinical trials.
    80. 80. THANK YOU
    81. 81. NOVEL METHODS
    82. 82. PERMANENT BREAST SEED IMPLANT  Percutaneous insertion of radioactive seeds (palladium-103 ) under US guidance  Use of LDR sources has the potential for improving the therapeutic ratio  A preplan is generated with optimal seed position and spacing to deliver the prescribed dose of 90 Gy to cover the lumpectomy cavity with a 1.5-cm margin.  Using a grid template 103Pd seeds are placed according to the preplan needle and seed distribution.
    83. 83. NONINVASIVE IMAGE-GUIDED BREAST BRACHYTHERAPY (ACCUBOOST) Breast immobilization Moderate compression between two mammography paddles. This technique achieved stable position of the breast and lumpectomy cavity for imaging and treatment.  Imaging is then performed using 30-kVp X-rays, similar to mammography, in the immobilized position and in the treatment plane. Imaged-guided target delineation  The lumpectomy cavity is delineated, usually with the assistance of radiopaque clips placed at the time of lumpectomy.  Using a target localization grid, the appropriate applicator size and position are selected to cover the lumpectomy cavity with an appropriately margin.  The selected tungsten alloy applicators are mounted on the mammography paddles centered on the target.
    84. 84. Treatment with collimated photon emission using 192 Ir HDR brachytherapy  Treatment is then delivered using directed photons in a parallel-opposed fashion from an 192Ir HDR source.  The process is then repeated along a second intersecting orthogonal axis in a sequential manner.  The orthogonal axes are usually oriented in craniocaudal and mediolateral directions so that presurgical mammography can be used to further assist and ensure appropriate target coverage
    85. 85.  In about 5-8 years, the ongoing studies will hopefully answer the questions related to patient selection, long-term outcome, and toxicity of the different techniques.  A modest reduction in initial treatment efficacy cannot be justified in patients with early breast cancer, who have an excellent prognosis with standard BCT including WBI.  For the coming years, patients should be carefully selected for APBI and closely followed with accurate documentation of any occurring events.
    86. 86. THANK YOU