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Radiation Therapy in Breast Cancer
DR ANKITA PATEL
MD RADIATION ONCOLOGY
CONSULTANT
DEPARTMENT OF RADIATION ONCOLOGY
APEX ...
INTRODUCTION
• Radiation plays an important role in the
management of breast cancer at all stages
including ductal carcino...
RATIONALE
• Most common site of recurrence is the local site
• Preventing recurrence also improves the quality
of life and...
INDICATIONS OF ADJUVANT
RADIOTHERAPY
• Tumour size >5cm
• Node positive
• All cases of BCS
• Positive or Close margin
Can be considered in high risk cases(not proved in
prospective randomised trials)
• High grade
• Young
• LVSI
• Inadequate...
RATIONALE
RADIATION THERAPY IS
BENEFICIAL AFTER BCS: EBCTCG –
2011 META-ANALYSIS:
• Lancet. Nov 12, 2011; 378(9804): 1707–1716.
• 17...
RADIATION THERAPY IS BENEFICIAL
AFTER BCS: EBCTCG – 2011 META-
ANALYSIS:
Lancet. Nov 12, 2011; 378(9804): 1707–1716.
FRACTION SIZE, FRACTIONATION AND
OAP:
FRACTION SIZE, FRACTIONATION AND
OAP:
HYPOFRACTIONATION POST MRM
LESSONS LEARNED OVER YEARS:
WHOLE BREAST RADIATION THERAPY
• CONVENTIONAL: 50.4Gy/28( Fractions50GY/25#) to PTV –
Delivered under DIBH for left breast...
TECHNIQUE FOR RADIOTHERAPY
• Positioning
• Immobilization
• Simulation
• Target Volume
• Treatment Planning
• Dose & Fract...
RTP SCAN AND TARGET CONTOURING
TARGET VOLUME
• AFTER BCS –
Whole breast radiotherapy + Regional nodes +lumpectomy
boost
• ...
3D PLANNING
• CT based imaging gives us
the ability to define regions
at risk of harboring disease
and organs we wish to a...
RTOG VOLUME COVERAGE
• With use of standard fields – For prescription of 50 Gy,
• 45 Gy covered
• – 74% of chest wall
• – ...
LEVEL 1 & 2 COVERAGE
3 FIELD SINGLE ISOCENTER TECHNIQUE
• 1 isocenter is used for both
tangents and supraclavicular
fields
• Tangents are ½ bea...
SINGLE ISO (CONTINUED)
3 FIELD DOUBLE ISOCENTER TECHNIQUE
• 1 iso for breast tangents,
separate iso for
supraclavicular field (needed
for tall pa...
• Tangent collimator is rotated to match slope of chest wall
• MLC leaves are used in tangent fields to form match line
• ...
DOUBLE ISO (CONTINUED)
SCV/PAB
RADIATION INDUCED TOXICITY
• Acute toxicity : skin discoloration
• Pneumonitis – 1% at 2 to 3 months post RT
• Lymphedema ...
CARDIAC TOXICITY
• 4456 women follow up post RT (median follow up 28 years)
• Treated between 1954 and 1984
• 1.76 fold in...
LAD AND MAJOR VESSELS
• Left sided breast RT–mid and distal LAD Right sided
breast RT with IMN -RCA
LEFT MAIN CORONARY AND LAD
• Consider RCA for right sided breast cancer when treating IMN
LAD MAY BE HARD TO SPARE
CLINICAL SOLUTIONS TO REDUCE
CARDIAC TOXICITY:
• Prone positions
• Breath hold techniques
Voluntary BH
Controlled BH
CLINICAL SOLUTIONS TO REDUCE
CARDIAC TOXICITY:PRONE POSITIONS
• PROS – Target position more
reproducible – Simple patient
...
CLINICAL SOLUTIONS TO REDUCE
CARDIAC TOXICITY: BREATH HOLD
• Displaces heart inferior and posterior to improve therapeutic...
• Real-time 3-Dimensional surface tracking consists of
three ceiling mounted stereo camera pods, two of
the pods are locat...
CEILING MOUNTED REAL
TIME IMAGING CAMERAS
Anatomy and isodose comparisons for a left
breast (Free-Breathing and Breathhold). The
separation between the heart and ch...
ACCELERATED PARTIAL BREAST
IRRADIATION
DESPITE BENEFITS OF RT….
• Standard radiation is inconvenient and expensive
• Not all patients will receive for these reas...
RATIONALE
• Vast majority of recurrences (80-90%) occur in the tumor
bed
• More convenient
• May allow more patients to un...
ARGUMENTS AGAINST PBI
• Why risk changing something that works? – No
expectation that PBI will improve upon local control
...
• Not all studies report low rate of recurrence outside of
the tumor bed
• MRI has been shown to reveal multifocal or mult...
PATIENT SELECTION CRITERIA FOR
APBI
APBI CONSENSUS STATEMENT FROM
THE ASTRO
“CAUTIONARY” GROUP ( ANY OF THESE
CRITERIA SHOULD INVOKE CAUTION AND
CONCERN WHEN CONSIDERING APBI)
METHODS OF DELIVERY
INTERSTITIAL BRACHYTHERAPY
• One of the first techniques utilized for the
administration of APBI
• For delivery of this tr...
BREAST TEMPLAT
INTERSTITIAL IMPLANTS (HDR AND LDR)
ADVANTAGE
• - Experience and long
follow up
• - Conformal
• - 4 -5 days
• - Well-toler...
PUBLISHED APBI RESULTS - CATHETER
BASED BRACHYTHERAPY
MAMMOSITE ™ BALLOON CATHETER
• Applicator can be placed into the lumpectomy
cavity at the time of surgery or in a separate...
MAMMOSITE PLACEMENT
• The balloon is inflated with saline solution mixed with a small
amount of contrast material to aid v...
INTRACAVITARY IMPLANTS
ADVANTAGE
• - Experience and studies with
long follow up
• - Conformal
• - 4 -5 days
• - Well-toler...
PUBLISHED APBI RESULTS - MAMMOSITE
INTRAOPERATIVE RADIATION
INTRA-OPERATIVE RT
ADVANTAGE
• Conformal
• - One treatment
• - Decreased interval from
surgery to RT
• - Phase I/II trials...
EXTERNAL BEAM RADIATION
ADVANTAGES OF EBRT
• The technique is non-invasive and the patient is not
subjected to a second invasive surgical procedur...
DISADVANTAGES OF EBRT APBI
• Breathing motion- The target may move during breathing and
the patient may be positioned diff...
3-D CONFORMAL EXTERNAL RT
ADVANTAGE
• - Non-invasive
• - Knowledge of final
pathology
• - 4 - 5 days
• - Homogeneous dose
...
3D CONFORMAL TECHNIQUES
• Vicini technique
• William-Beaumont Hospital, MI
• Formentitechnique
• New York University, NY
•...
VICINI TECHNIQUE
Multiple photon fields 3.85 Gy X 10 fractions BID / 1 weeks RTOG/NSABP
fractionation scheme
FORMENTI/PRONE TECHNIQUE
• Photon technique (usually 2 fields)
• 6.0 Gy X 5 fractions 2 weeks
TAGHIAN/MGH TECHNIQUE
• 2 mini-tangents and en face electrons 4.0 Gy X 8-10 fractions BID / 4
days
GUIDELINES TAGHIAN/MGH TECHNIQUE
• Seroma should have 4-6 clips
• Margins: 1.5 to 2 cm
• Ratio PTV/breast volume <20%
• No...
PUBLISHED APBI RESULTS - 3D
CONFORMAL EXTERNAL BEAM RT
TARGET DEFINITION
• Surgical clips useful for tumor bed definition
PHASE III TRIALS
VMAT FOR BREAST TREATMENT
• Useful for high risk patients,
better target coverage
• Multifield and higher mean
heart dose,...
PROTONS THERAPY
PROTONS MAY BE USEFUL FOR..
• Advanced disease
• IMN involvement (R or L sided)
• Cardiotoxic chemo
• Young age
• Permanen...
PRAGMATIC RANDOMIZED TRIAL OF PROTON VS.
PHOTON THERAPY FOR PATIENTS WITH NON-
METASTATIC BREAST CANCER RECEIVING
COMPREHE...
FLASH RADIOTHERAPY: THE NEXT TECHNOLOGICAL
ADVANCE IN RADIATION THERAPY?
• FLASH radiotherapy involves the ultra-fast deli...
• One mechanism is the prevention of cytokine activation, such
as the release of transforming growth factor-beta, which is...
• Deliver ultra-high dose rates is a modified ELEKTA Precise
machine developed by investigators from the University
Hospit...
ESTABLISHING THE ROLE OF STEREOTACTIC ABLATIVE
BODY RADIOTHERAPY IN EARLY-STAGE BREAST
CANCER
• Various trials are ongoing...
RADIOTHERAPY IN CARCINOMA BREAST (EARLY AND LOCALLY ADVANCED)
RADIOTHERAPY IN CARCINOMA BREAST (EARLY AND LOCALLY ADVANCED)
RADIOTHERAPY IN CARCINOMA BREAST (EARLY AND LOCALLY ADVANCED)
RADIOTHERAPY IN CARCINOMA BREAST (EARLY AND LOCALLY ADVANCED)
RADIOTHERAPY IN CARCINOMA BREAST (EARLY AND LOCALLY ADVANCED)
RADIOTHERAPY IN CARCINOMA BREAST (EARLY AND LOCALLY ADVANCED)
RADIOTHERAPY IN CARCINOMA BREAST (EARLY AND LOCALLY ADVANCED)
RADIOTHERAPY IN CARCINOMA BREAST (EARLY AND LOCALLY ADVANCED)
RADIOTHERAPY IN CARCINOMA BREAST (EARLY AND LOCALLY ADVANCED)
RADIOTHERAPY IN CARCINOMA BREAST (EARLY AND LOCALLY ADVANCED)
RADIOTHERAPY IN CARCINOMA BREAST (EARLY AND LOCALLY ADVANCED)
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RADIOTHERAPY IN CARCINOMA BREAST (EARLY AND LOCALLY ADVANCED)

  1. 1. Radiation Therapy in Breast Cancer DR ANKITA PATEL MD RADIATION ONCOLOGY CONSULTANT DEPARTMENT OF RADIATION ONCOLOGY APEX HOSPITAL
  2. 2. INTRODUCTION • Radiation plays an important role in the management of breast cancer at all stages including ductal carcinoma in situ, early-stage disease (as a component of breast conservation), and locally advanced disease (as an adjuvant treatment after mastectomy). • Radiation is also a highly effective palliative modality.
  3. 3. RATIONALE • Most common site of recurrence is the local site • Preventing recurrence also improves the quality of life and overall survival • Not all recurrences are salvageable
  4. 4. INDICATIONS OF ADJUVANT RADIOTHERAPY • Tumour size >5cm • Node positive • All cases of BCS • Positive or Close margin
  5. 5. Can be considered in high risk cases(not proved in prospective randomised trials) • High grade • Young • LVSI • Inadequate nodal dissection • Triple negative receptor status • Her-2 positive tumours • Skin,nipple or pectoralis muscle invasion
  6. 6. RATIONALE
  7. 7. RADIATION THERAPY IS BENEFICIAL AFTER BCS: EBCTCG – 2011 META-ANALYSIS: • Lancet. Nov 12, 2011; 378(9804): 1707–1716. • 17 Randomized Trials N +ve & N –ve = 10801 Patients • 1 death due to breast cancer can be avoided for every 4 recurrences prevented.
  8. 8. RADIATION THERAPY IS BENEFICIAL AFTER BCS: EBCTCG – 2011 META- ANALYSIS: Lancet. Nov 12, 2011; 378(9804): 1707–1716.
  9. 9. FRACTION SIZE, FRACTIONATION AND OAP:
  10. 10. FRACTION SIZE, FRACTIONATION AND OAP:
  11. 11. HYPOFRACTIONATION POST MRM
  12. 12. LESSONS LEARNED OVER YEARS:
  13. 13. WHOLE BREAST RADIATION THERAPY • CONVENTIONAL: 50.4Gy/28( Fractions50GY/25#) to PTV – Delivered under DIBH for left breast. • HYPOFRACTIONATION: 42.6Gy/16 fractions to PTV – Delivered under DIBH for left breast. • 10-16Gy boost to lumpectomy cavity for all patients.FB • Achieve uniform whole breast coverage using opposing tangential fields with field-in-field and/or wedge technique.
  14. 14. TECHNIQUE FOR RADIOTHERAPY • Positioning • Immobilization • Simulation • Target Volume • Treatment Planning • Dose & Fractionation • Set Up Verification and treatment delivery
  15. 15. RTP SCAN AND TARGET CONTOURING TARGET VOLUME • AFTER BCS – Whole breast radiotherapy + Regional nodes +lumpectomy boost • AFTER MASTECTOMY chest wall – mastectomy scar – regional nodes
  16. 16. 3D PLANNING • CT based imaging gives us the ability to define regions at risk of harboring disease and organs we wish to avoid based on 3D anatomy • Contours required for some modalities (IMRT, Protons)
  17. 17. RTOG VOLUME COVERAGE • With use of standard fields – For prescription of 50 Gy, • 45 Gy covered • – 74% of chest wall • – 84% of Level 1 LN • – 88% of Level 2 LN • – 93% of Level 3 LN • – 84% of SCV LN • – 80% of IMN • Important to remember that outcomes have been very good with this coverage, but perhaps we can do better with defined contours while keeping in mind normal tissue toxicity • Fontanilla, et al Practical Radiation Oncology 2012
  18. 18. LEVEL 1 & 2 COVERAGE
  19. 19. 3 FIELD SINGLE ISOCENTER TECHNIQUE • 1 isocenter is used for both tangents and supraclavicular fields • Tangents are ½ beam blocked superiorly, sclav is ½ beam blocked inferiorly to avoid overlap of fields • Collimator for tangent fields typically set to 0, MLC leaves are drawn in to block lung
  20. 20. SINGLE ISO (CONTINUED)
  21. 21. 3 FIELD DOUBLE ISOCENTER TECHNIQUE • 1 iso for breast tangents, separate iso for supraclavicular field (needed for tall patients or patients that need high SCV field) • In order to match superior border of tangents to inferior border of s’clav, couch kicks are needed for tangents to account for beam divergence
  22. 22. • Tangent collimator is rotated to match slope of chest wall • MLC leaves are used in tangent fields to form match line • Sclavfield is ½ beam blocked inferiorly
  23. 23. DOUBLE ISO (CONTINUED)
  24. 24. SCV/PAB
  25. 25. RADIATION INDUCED TOXICITY • Acute toxicity : skin discoloration • Pneumonitis – 1% at 2 to 3 months post RT • Lymphedema – Fluid buildup due to damage to lymphatic drainage – Weeks to years post RT • Cardiac toxicity
  26. 26. CARDIAC TOXICITY • 4456 women follow up post RT (median follow up 28 years) • Treated between 1954 and 1984 • 1.76 fold increase with surgery + RT compared to surgery alone • 1.56 fold increase for left versus right breast RT • Rates of major coronary events increased linearly with mean dose to heart by 7.4%/Gy (95% confidence interval) with no apparent threshold
  27. 27. LAD AND MAJOR VESSELS • Left sided breast RT–mid and distal LAD Right sided breast RT with IMN -RCA
  28. 28. LEFT MAIN CORONARY AND LAD • Consider RCA for right sided breast cancer when treating IMN
  29. 29. LAD MAY BE HARD TO SPARE
  30. 30. CLINICAL SOLUTIONS TO REDUCE CARDIAC TOXICITY: • Prone positions • Breath hold techniques Voluntary BH Controlled BH
  31. 31. CLINICAL SOLUTIONS TO REDUCE CARDIAC TOXICITY:PRONE POSITIONS • PROS – Target position more reproducible – Simple patient setup – Reducing the contact between breast tissue and chest walls (large breast patients) • CONS: – Patient comfort – Variability in contralateral breast – Less advantage for small breast patients •
  32. 32. CLINICAL SOLUTIONS TO REDUCE CARDIAC TOXICITY: BREATH HOLD • Displaces heart inferior and posterior to improve therapeutic ratio for many patients • Requires verification of position
  33. 33. • Real-time 3-Dimensional surface tracking consists of three ceiling mounted stereo camera pods, two of the pods are located laterally to the treatment couch and the other is one is located centrally at the foot of the treatment couch. • The real-time surface image can be registered with the planned surface contour and provides the patient’s real-time positioning offsets. The real time offsets is utilized to align patients initially before treatment and monitor the patient during treatment.
  34. 34. CEILING MOUNTED REAL TIME IMAGING CAMERAS
  35. 35. Anatomy and isodose comparisons for a left breast (Free-Breathing and Breathhold). The separation between the heart and chest wall from 4.15 cm to 7.66 cm.
  36. 36. ACCELERATED PARTIAL BREAST IRRADIATION
  37. 37. DESPITE BENEFITS OF RT…. • Standard radiation is inconvenient and expensive • Not all patients will receive for these reasons and “Financial Toxicity” to patients is becoming an increasing concern • APBI offers a short treatment (1 day to 2 weeks) and may allow more patients to receive RT and some regimens are less expensive; patients at a distance need only a short hotel stay to receive treatment
  38. 38. RATIONALE • Vast majority of recurrences (80-90%) occur in the tumor bed • More convenient • May allow more patients to undergo BCT • Decreased exposure of normal tissues • Whole breast volume was chosen in an era of aggressive surgical treatment and skepticism that BCT would prove a feasible option • Improvements in imaging allow for better visualization of tumor bed Veronesi et al. 2002; Clark RM, et al.; Athos 2002
  39. 39. ARGUMENTS AGAINST PBI • Why risk changing something that works? – No expectation that PBI will improve upon local control • EBCTG meta-analysis demonstrated OS benefit for WBI – Could be more to lose than LC • Shorter WBI courses are another alternative – With Phase III RTC and longer follow up • EBCTG 2005; Whelan et al. 2010; Dewer et al. 2007
  40. 40. • Not all studies report low rate of recurrence outside of the tumor bed • MRI has been shown to reveal multifocal or multicentric disease, but this imaging may not be available for all patients receiving PBI & MRI is costly • Even with more extensive surgery, RT is of benefit (quadrantectomy) • Bartelink et al. 2001; Al-Hallaq, et al. 2006; Veronisi, 2002
  41. 41. PATIENT SELECTION CRITERIA FOR APBI
  42. 42. APBI CONSENSUS STATEMENT FROM THE ASTRO
  43. 43. “CAUTIONARY” GROUP ( ANY OF THESE CRITERIA SHOULD INVOKE CAUTION AND CONCERN WHEN CONSIDERING APBI)
  44. 44. METHODS OF DELIVERY
  45. 45. INTERSTITIAL BRACHYTHERAPY • One of the first techniques utilized for the administration of APBI • For delivery of this treatment, interstitial catheters are placed at the time of surgery or at a separate surgical procedure • Advantage of placing catheters at the time of resection is sparing an additional surgical procedure but no final pathology evaluation prior to RT • # of catheters and planes depends on the target volume • Implants are planned to cover the tumor bed + 1-3 cm margin. Can be delivered with LDR or HDR.
  46. 46. BREAST TEMPLAT
  47. 47. INTERSTITIAL IMPLANTS (HDR AND LDR) ADVANTAGE • - Experience and long follow up • - Conformal • - 4 -5 days • - Well-tolerated DISADVANTAGE • - Invasive procedure • - Infection, hematoma risks • - Formal training • - Operator dependent • - Requires hospital stay (LDR) or multiple visits with catheters in place (HDR
  48. 48. PUBLISHED APBI RESULTS - CATHETER BASED BRACHYTHERAPY
  49. 49. MAMMOSITE ™ BALLOON CATHETER • Applicator can be placed into the lumpectomy cavity at the time of surgery or in a separate procedure after surgery(USG guided). • Dose: 34 Gy over 10 fractions (3.4 Gy per fraction, BID). The prescription point is 1 cm from the balloon surface with a minimum of 6 hours between fractions on the same day.
  50. 50. MAMMOSITE PLACEMENT • The balloon is inflated with saline solution mixed with a small amount of contrast material to aid visualization. The balloon is inflated to a size that would completely fill the lumpectomy cavity. • 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.
  51. 51. INTRACAVITARY IMPLANTS ADVANTAGE • - Experience and studies with long follow up • - Conformal • - 4 -5 days • - Well-tolerated • - Relative ease of use (compared to interstitial brachytherapy) DISADVANTAGE • - Invasive procedure • - Infection, hematoma risks • - Formal training • - Steep learning curve • - Limitations if close to skin
  52. 52. PUBLISHED APBI RESULTS - MAMMOSITE
  53. 53. INTRAOPERATIVE RADIATION
  54. 54. INTRA-OPERATIVE RT ADVANTAGE • Conformal • - One treatment • - Decreased interval from surgery to RT • - Phase I/II trials promising • - Phase III with early results DISADVANTAGE • Invasive procedure - RT delivered at time of surgery for all patients before the availability of final path - Late effect of a large single dose - Dose distribution - Biological impact - Availability
  55. 55. EXTERNAL BEAM RADIATION
  56. 56. ADVANTAGES OF EBRT • The technique is non-invasive and the patient is not subjected to a second invasive surgical procedure or anesthesia, thereby reducing the potential risk of complications. • The technique has potential for widespread availability since most radiation therapy centers already perform 3D-CRT for other cancers. • • Treatment results with external beam may be more uniform between radiation oncologists .
  57. 57. DISADVANTAGES OF EBRT APBI • Breathing motion- The target may move during breathing and the patient may be positioned differently for different fractions. • To avoid missing the planned target,a large treatment volume is used which delivers higher doses to normal breast tissue since the PTV around the lumpectomy cavity is increased to account for breathing and setup errors. • The identification and contouring of the lumpectomy cavity is another issue. the GTV and CTV are generally defined as the contouring of a seroma within the lumpectomy cavity. However, the delineation of the seroma could vary among different observers and even among experienced ones.
  58. 58. 3-D CONFORMAL EXTERNAL RT ADVANTAGE • - Non-invasive • - Knowledge of final pathology • - 4 - 5 days • - Homogeneous dose distribution • - Widely available • - Less costly • - Requires less specialized training DISADVANTAGE • - Optimal doses? • - Optimal fractionation? • - Patient set up • - Tolerance of non-target tissues to RT • - Long term cosmesis • - Greater dose to uninvolved breast tissue • - Shorter follow up
  59. 59. 3D CONFORMAL TECHNIQUES • Vicini technique • William-Beaumont Hospital, MI • Formentitechnique • New York University, NY • MGH technique • Boston, MA • Others, IMRT, protons, etc
  60. 60. VICINI TECHNIQUE Multiple photon fields 3.85 Gy X 10 fractions BID / 1 weeks RTOG/NSABP fractionation scheme
  61. 61. FORMENTI/PRONE TECHNIQUE • Photon technique (usually 2 fields) • 6.0 Gy X 5 fractions 2 weeks
  62. 62. TAGHIAN/MGH TECHNIQUE • 2 mini-tangents and en face electrons 4.0 Gy X 8-10 fractions BID / 4 days
  63. 63. GUIDELINES TAGHIAN/MGH TECHNIQUE • Seroma should have 4-6 clips • Margins: 1.5 to 2 cm • Ratio PTV/breast volume <20% • Non-target breast volume receiving 50% of dose <50% • 95% isodose line covers 95% of the PTV • Use IGRT (VisionRT) for accurate set-up • Lung volume: ILV-20Gy: <3% ILV-10Gy: <10% ILV-5Gy: <20% Recht, JCO 2013
  64. 64. PUBLISHED APBI RESULTS - 3D CONFORMAL EXTERNAL BEAM RT
  65. 65. TARGET DEFINITION • Surgical clips useful for tumor bed definition
  66. 66. PHASE III TRIALS
  67. 67. VMAT FOR BREAST TREATMENT • Useful for high risk patients, better target coverage • Multifield and higher mean heart dose, lung V5 • Lower lung V20 • Large arcs, avoid entering through contralateral breast • Daily CBCT • IMRT can be used without multiple arcs to provide some benefit without low dose spread
  68. 68. PROTONS THERAPY
  69. 69. PROTONS MAY BE USEFUL FOR.. • Advanced disease • IMN involvement (R or L sided) • Cardiotoxic chemo • Young age • Permanent implants • Poor cardiac anatomy • Left medial tumors • Pre-existing cardiac disease • Decreased arm mobility • Predisposition for additional cancers (P53 mutations)
  70. 70. PRAGMATIC RANDOMIZED TRIAL OF PROTON VS. PHOTON THERAPY FOR PATIENTS WITH NON- METASTATIC BREAST CANCER RECEIVING COMPREHENSIVE NODAL RADIATION
  71. 71. FLASH RADIOTHERAPY: THE NEXT TECHNOLOGICAL ADVANCE IN RADIATION THERAPY? • FLASH radiotherapy involves the ultra-fast delivery of radiation treatment at dose rates several orders of magnitude greater than those currently in routine clinical practice. • Experimental data from a variety of in vitro cell and tissue culture models, supplemented more recently by animal studies, show that ultra-fast delivery of radiotherapy (in excess of 40 Gy/s) leads to sparing of normal tissues when compared with normal dose rates (about 0.03 Gy/s).
  72. 72. • One mechanism is the prevention of cytokine activation, such as the release of transforming growth factor-beta, which is not initiated in normal lung following FLASH irradiation. • Another, and more likely mechanism, concerns the role of oxygen. FLASH radiation consumes all available oxygen and liberates significantly more electrons, resulting in many more ionisation events than at conventional dose rates. This maximises the differences in redox metabolism (reduction oxidation reaction) and free radical chemistry between cancers and normal tissue. • FLASH radiotherapy seems more effective in killing hypoxic cancerous cells than standard dose rate radiotherapy with the added advantage of sparing normal tissue.
  73. 73. • Deliver ultra-high dose rates is a modified ELEKTA Precise machine developed by investigators from the University Hospitals of Skane and Lund in Sweden . Fine tuning is still required to reduce variation in dose delivery and beam flatness, but it is estimated that the machine may be ready to treat humans in 35 years .
  74. 74. ESTABLISHING THE ROLE OF STEREOTACTIC ABLATIVE BODY RADIOTHERAPY IN EARLY-STAGE BREAST CANCER • Various trials are ongoing to explore the technique of SABR further, especially in early-stage elderly breast cancer patients and, in addition, to address the many radiobiological, technical, and toxicity issues that may arise through its use to deliver safe, quality assured, evidence-based radiotherapy
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RADIOTHERAPY IN CARCINOMA BREAST EARLY AND ADVANCED STAGE

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