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Θεραπευτική αντιμετώπιση καρκίνου μαστού – Ακτινοθεραπεία            Τεχνική & Πρόοδος,[object Object], ΕΛΛΗΝΙΚΗ ΣΧΟΛΗ ΜΑΣΤΟΛΟΓΙΑΣ:,[object Object], Β' ΚΥΚΛΟΣ ΣΠΟΥΔΩΝ - 4η ΣΕΙΡΑ ΑΘΗΜΑΤΩΝ,   16-17 ΣΕΠΤΕΜΒΡΙΟΥ 2011, ,[object Object],         ΑΙΓΛΗ ΖΑΠΠΕΙΟΥ,[object Object],ΒΑΚΑΛΗΣ ΞΕΝΟΦΩΝ,[object Object],ΑΚΤΙΝΟΘΕΡΑΠΕΥΤΗΣ ΟΓΚΟΛΟΓΟΣ,[object Object],ΙΑΤΡΙΚΟ ΚΕΝΤΡΟ ΑΘΗΝΩΝ,[object Object],&,[object Object],401 ΣΤΡΑΤΙΩΤΙΚΟ ΝΟΣ. ΑΘΗΝΩΝ,[object Object]
Historical Perspective,[object Object],Interstitial Radium Brachytherapy for Breast Cancer, 1917,[object Object],Radiotherapy for Breast Cancer, London Hospital,  c. 1917,[object Object]
Prospective Randomized Trials of Lumpectomy +/- Radiotherapy,[object Object]
42 000 women,[object Object],in 78 randomized trials,[object Object],Mastectomy node-pos,[object Object],↓LR: 17%,[object Object],↓DSM: 5.4%,[object Object],BCS node-neg,[object Object],BCS node-pos,[object Object],↓LR: 16%,[object Object],↓DSM: 5%,[object Object],↓LR: 30%,[object Object],↓DSM: 7%,[object Object],Lancet 2005; 366: 2087,[object Object]
Lancet 2005; 366: 2087,[object Object]
Radiation Therapy for Early Stage Breast Cancer Following Lumpectomy,[object Object],Whole Breast Irradiation,[object Object],Rationale: Addition of whole breast irradiation following lumpectomy yields local control rates comparable to mastectomy,[object Object],Treatment: Whole breast irradiation,[object Object],[object Object]
 60 Gy to the lumpectomy cavity + margin
1.8 – 2 Gy fraction given 5 days/ week
5 – 7 week total treatment duration,[object Object]
Vakalis new techniques in breast radiotherapy
Vakalis new techniques in breast radiotherapy
Image-based Conformal Radiation Therapy: ,[object Object],60 Gy,[object Object],62 Gy,[object Object],50 Gy,[object Object],20 Gy,[object Object],45 Gy,[object Object],axial,[object Object],sagittal,[object Object],Left Breast,[object Object]
Example of guidelines for PMRT,[object Object],RT is recommended to patients scoring ≥ 3 (Cambridge, UK),[object Object]
Vakalis new techniques in breast radiotherapy
Accelerated Whole Breast Irradiation:Reducing the burden of care,[object Object],Canadian Phase III Randomized Trial:,[object Object],42.5 Gy – 16 fractions – 22 days   vs.,[object Object],		50 Gy – 25 fractions – 35 days,[object Object],1,234 patients          	-  T1 – T2, N 0  (80% T1)-  ER positive - 71% 	-  Median F/U:  69 months,[object Object]
Randomized Boost Trials,[object Object]
Vakalis new techniques in breast radiotherapy
Accelerated Whole Breast Irradiation:A Phase II clinical trial of a 4 week course of RT for breast cancer using hypo fractionated IMRT with a concomitant boost.,[object Object],4 week course – 20 treatments,[object Object], 45 Gy whole breast dose,[object Object], 56 Gy boost dose,[object Object],Results:,[object Object],  16 patients treated,[object Object],  Acute toxicity: Grade I 57%, Grade II 43%,[object Object]
Vakalis new techniques in breast radiotherapy
     Regional Nodal RTAwaiting results of two large trials (France and EORTC),[object Object]
Vakalis new techniques in breast radiotherapy
Vakalis new techniques in breast radiotherapy
Full SCLV Field,[object Object]
IM Nodal Radiation Technique,[object Object]
Vakalis new techniques in breast radiotherapy
Cured from,[object Object],Breast Cancer,[object Object],Died of Cardiac,[object Object],Toxicity ,[object Object],Adapted from Larry Marks, Duke,[object Object]
Overall survival: radical mastectomy + / - RT,[object Object],First 10 years,[object Object],Next 25 years,[object Object],Cuzick et al: Recent Results Cancer Research 111:108-129, 1988,[object Object]
XRT worse,[object Object],XRT better,[object Object],XRT better,[object Object],XRT worse,[object Object],XRT better,[object Object],XRT worse,[object Object],Overall Survival,[object Object],Cardiac Mortality,[object Object],Breast Ca  Mortality,[object Object],Cuzick JCO 12:452, 1994,[object Object]
Vakalis new techniques in breast radiotherapy
Vakalis new techniques in breast radiotherapy
The shape of the breast and the position of the heart in relation to the chest wall can vary enormously,[object Object]
Vakalis new techniques in breast radiotherapy
Decrease cardiac Exposure to RT,[object Object],Partial Breast Irradiation,[object Object],Decubitus or Prone positions,[object Object],Breath Hold Technique,[object Object],Respiratory gating technique,[object Object],Proton therapy,[object Object]
Patient’s Position,[object Object],Prone and IMRT,[object Object],Lateral Decubitus,[object Object],Campana et al 2005,[object Object],DeWyngaert et al 2007,[object Object]
Vakalis new techniques in breast radiotherapy
Prone Breast RT,[object Object]
Goodman,[object Object],Figure 1a. Customized prone breast board with adjustable aperture and wedge for contralateral breast.Figure 1b. Ipsilateral breast and anterior chest wall hang in a dependent fashion away from the thorax while the ipsilateral arm is placed above the head,[object Object]
Goodman,[object Object],Figure 6.  Left breast irradiation using prone breast IMRT technique can spare left ventricle and coronary arteries.,[object Object]
3-DCRT for left prone breast radiation:,[object Object],Improved targeting and avoidance of lung,[object Object],Sagittal,[object Object],45 Gy,[object Object],60 Gy,[object Object],Lumpectomy,[object Object],50 Gy,[object Object],PTV,[object Object],Transaxial,[object Object]
Intensity Modulated Radiotherapy (IMRT),[object Object], … + Image Guidance (IGRT),[object Object],Breast is a moving target !,[object Object]
Double Trouble !,[object Object],Heart,[object Object]
Solution = Gated Radiotherapy,[object Object],Heart,[object Object]
Varian RPM respiratory management system,[object Object]
Deep Inspiration Breath-Hold (DIBH),[object Object],Rosenzweig  Int. J. Radiation Oncology Biol. Phys. 2000,[object Object]
Increase spatial separation between target and organs at risk,[object Object]
     Cardiac Sparing,[object Object],V5 Volume receiving 5% of the dose,[object Object]
Pattern of In-Breast Cancer Recurrences Following  Breast Conserving Therapy,[object Object],The majority of cancer recurrences in the treated breast occur at the lumpectomy site,[object Object]
Potential Benefits of Partial Breast Irradiation,[object Object],Reduce time and inconvenience of BCT,[object Object],Improve documented underutilization of breast conserving therapy (BCT)?,[object Object],Potentially reduce acute and chronic toxicity,[object Object],Reduce burden of care for patients,[object Object],Eliminate scheduling problems with systemic chemotherapy,[object Object]
Rationale for Partial Breast Irradiation	(PBI),[object Object],10%-40% of those who are candidates for breast conservation therapy actually do not receive it.,[object Object],Why?,[object Object],Patient’s choice,[object Object],Complex and prolonged treatment course can be inconvenient for those with poor access to a radiation facility, the elderly and working women,[object Object],Physician bias,[object Object]
Techniques for PBI,[object Object],Interstitial brachytherapy  with HDR or LDR,[object Object],Intracavitarybrachytherapy with Mammosite,[object Object],Intraoperative electron beam therapy,[object Object],3D conformal radiation therapy,[object Object],Proton beam,[object Object]
Partial breast irradiation techniques,[object Object]
Three Established Methods For PBI,[object Object],Mammosite®,[object Object],Multi Catheter,[object Object],3-D Conformal,[object Object]
Accelerated Partial Breast Irradiation,[object Object],Treatments delivered twice daily (with treatments separated by six hours) for 10 treatments delivered in 5 treatment days.,[object Object],Delivery of radiation limited to lumpectomy site with a margin of normal tissue.,[object Object],Each treatment takes approximately 10 minutes to deliver.,[object Object]
Target definition,[object Object]
Accelerated Partial Breast Irradiation,[object Object],Benefits:,[object Object],Limited radiation exposure to normal tissue,[object Object],Treatments completed in one week instead of six weeks,[object Object]
Accelerated Partial Breast Irradiation,[object Object],Limitations:,[object Object],May require additional surgical procedure ,[object Object],Requires twice daily treatment,[object Object],Newer modality with far fewer patients treated and much shorter follow-up,[object Object],As of now, no direct comparison with standard radiation,[object Object]
Vakalis new techniques in breast radiotherapy
Who is eligible for PBI?	(Off study),[object Object],Tumors < 3 cm,[object Object],Negative margins (> 2mm),[object Object],Node negative,[object Object],Invasive ductal carcinoma or DCIS,[object Object],Older women (>45 yrs),[object Object],Revised Consensus Statement for Accelerated Partial Breast Irradiation, 12/8/05,[object Object]
Interstitial brachytherapy,[object Object],Catheters are placed intraoperatively or later; usually 2 planes,[object Object],Typical doses with HDR = 30-36 Gy and LDR = 45-60 Gy,[object Object],Treatment delivered over one week.,[object Object]
Breast Brachytherapy,[object Object]
Multi-Catheter Brachytherapy,[object Object]
Dose Distribution of MultiCatheter PBI,[object Object],PTV,[object Object],100% isodose,[object Object]
Breast Appearance Following Multi-catheter Brachytherapy,[object Object],5 years post treatment,[object Object]
Patient Selection for Breast Brachytherapy,[object Object],Patients older than 45,[object Object],Tumors less than 2 cm. in size,[object Object],>2mm. Margins,[object Object],Preferably Infiltrating Ductal or loclized low grade DCIS.  No Lobular CA,[object Object],There must be at least 7mm. of tissue between the catheter surface and the skin of the breast.,[object Object]
Advantages of Breast Brachytherapy vs. External Beam RT,[object Object],6 weeks (30 fractions),[object Object],Homogeneous dose,[object Object],Logistical problem for patients,[object Object],Difficult for frail, elderly, or chronically ill patients,[object Object],Interferes with schedule of working women,[object Object],Some BCT candidates will opt for mastectomy,[object Object],5 days (10 fractions),[object Object],Dose is higher to tissue at greatest risk for sub-clinical malignant cells,[object Object],Reduction in skin, cardiac and lung dose,[object Object],Ideal for patients who live far from RT Center,[object Object],Convenient,[object Object],May increase number of women treated with BCT,[object Object]
Disadvantages of Breast Brachytherapy vs. External Beam RT,[object Object],Noninvasive,[object Object],Can cover nodal regions,[object Object],Treats multi-centric carcinoma,[object Object],Low complication rate,[object Object],Linear accelerators widely available,[object Object],Most radiation oncologists experienced	,[object Object],Invasive,[object Object],Not useful for treatment of nodal basins,[object Object],May miss tumor foci in other quadrants,[object Object],Low, but definite risk of infection and/or fat necrosis,[object Object],Requires special skills for performing; in placing catheters and dosimetry,[object Object]
MultiCatheter PBI:HDR/ LDR,[object Object],61 mo.,[object Object],5%,[object Object],89%,[object Object],61 y,[object Object],1.4 cm,[object Object],17.5%,[object Object],Average:,[object Object]
Breast Brachytherapy,[object Object],There has got to be a better way than all of those needles.,[object Object],Mammosite device from Proxima Therapeutics may be the answer.,[object Object],FDA approved the device in May 2002,[object Object]
MammoSite PBI,[object Object],Mammosite® Breast Brachytherapy Applicator,[object Object],[object Object]
Dual lumen single catheter 		with expandable balloon at 		end
  	Balloon expands to fill the 	lumpectomy cavity
  	Radiation dose prescribed to 1 	cm beyond balloon surface
    Uses 192Ir (HDR) as the source
 	FDA approval May 2002,[object Object]
5th Int. Meeting ISIORT Madrid, June 2008,[object Object],GTV,[object Object],PTV,[object Object],Skin,[object Object],Volume Definition,[object Object],PTV:	GTV + 1.5 – 2.0 (clinical margin) + 0.5 (setup margin),[object Object], 	excluding skin and chest wall,[object Object],Skin:	5 mm depth below skin surface,[object Object]
Difficulties with Mammosite,[object Object],Balloon must conform to cavity shape without air gaps. Device explanted in ~ 10-15% of pts.,[object Object],Ideal is to have 7 mm b/w balloon and skin to decrease risk of erythema.,[object Object],Very dependent on surgical placement.,[object Object]
CT Planning for MammositeBrachytherapy,[object Object],Isodose Lines,[object Object],50%,[object Object],80%,[object Object],100%,[object Object],120%,[object Object],140%,[object Object],200%,[object Object],Mammosite® balloon,[object Object]
Prescription Dose,[object Object],[object Object]
10 fractions over 5 -7days3-Dimensional rendering of applicator surface and prescription dose cloud.,[object Object]
Day 2 on treatment,[object Object]
 Day 2 on treatment,[object Object]
2 weeks post treatment,[object Object]
4 months after PBI,[object Object]
Breast Appearance after MammoSite®,[object Object],3 years post treatment,[object Object]
MammoSite PBI,[object Object],Average:,[object Object],4%,[object Object],0%,[object Object],83%,[object Object],64 y,[object Object],26 mo,[object Object],1 cm,[object Object]
Toxicities of Mammosite,[object Object],Seroma formation:  Risk is increased with open technique for placement.  In Beaumont series, found 60% risk with open cavity vs. 30% in closed cavity; overall rate of 45%, with 10% symptomatic.,[object Object],Fat necrosis: Risk may be slightly lower than with HDR and no difference with placement technique.,[object Object]
Conclusion,[object Object],The MammoSite RTS is the most commonly used PBI technique,[object Object],MammoSite is minimally invasive, offers acceptable cosmetic results, and induces mild side effects,[object Object],The duration of treatment is only five days making it more convenient for patients ,[object Object],The MammoSite RTS has criteria which prevent some patients from eligibility,[object Object],New devices such as SAVI, ClearPath, and Contura are overcoming those limitations,[object Object]
… and Mammosite begat ….,[object Object],Contura,[object Object],ClearPath™,[object Object],SAVI,[object Object],5th Int. Meeting ISIORT Madrid, June 2008,[object Object]
PBI:  3D-CRT Target definition,[object Object]
PBI:  3D-CRT Beam Arrangement,[object Object],3.85 Gy BID x 10 fractions,[object Object]
PBI:  3D-CRT Isodose Distribution,[object Object],3850 3752 3655 3557 3460,[object Object],axial,[object Object],sagittal,[object Object],coronal,[object Object]
3-DCRT PBI,[object Object],Summary:,[object Object],273,[object Object],63,[object Object],21,[object Object],0.9,[object Object],< 1,[object Object],0,[object Object]
Accelerated Partial Breast Irradiation:Summary,[object Object],Accelerated partial breast irradiation allows patients to complete a course of treatment in one week as opposed to the standard six weeks.,[object Object],Treatment limited to part of the breast may be associated with less morbidity of treatment and better cosmetic outcome.,[object Object],Hopefully, the randomized, prospective NSABP trial will answer the question of equivalence of partial and standard breast irradiation.,[object Object]
Stage 0, I-II breast cancer treated by lumpectomy,[object Object],Randomization,[object Object],WBI,[object Object],[object Object],Fractions to the whole breast ,[object Object],followed by boost to 60 -66.6 Gy,[object Object],PBI,[object Object],[object Object],Mammosite® or ,[object Object],Multicatheter brachytherapy ,[object Object],OR,[object Object],[object Object],3D-CRT,[object Object],NSABP B-39/RTOG 0413 TrialPhase III,[object Object]
Endpoints,[object Object],[object Object]
 Secondary:Distant disease-free survival,[object Object],Overall survival,[object Object],QOL: Cosmesis, fatigue, symptoms, burden of care,[object Object]
5th Int. Meeting ISIORT Madrid, June 2008,[object Object],ZeissIntrabeam®,[object Object],[object Object]
Spherical applicators with diameters of 15-50 mm in steps of 5 mm
Dose rate of about 2 Gy/min at 1 cm in water,[object Object]
The pliable breast tissue is wrapped around the applicator. Subcutaneous stitches aid conformation, while ensuring that the skin is at least 1cm from the applicator surface.,[object Object]
Vakalis new techniques in breast radiotherapy
Vakalis new techniques in breast radiotherapy
Intraoperative Radiation Therapy (IORT) for PBI,[object Object],TARGIT trial is comparing whole breast irradiation to IORT delivering a single dose of 20 Gy. Primary accrual is in Europe.,[object Object],Using the Intrabeam Photon Radiosurgery System, 50 kV x-rays.,[object Object],Trial has enrolled 900 patients with target of 2200 patients. ,[object Object]
Trials of partial breast RT,[object Object]
What about IMRT?,[object Object]
Γιατί χρειαζόμαστε την IMRT ; ,[object Object],[object Object],   της δόσης ενδεχομένως συνοδεύεται από μικρότερη οξεία και χρόνια,[object Object],   τοξικότητα (δέρμα, μαζικό παρέγχυμα),[object Object],[object Object],  αριστερού μαστού) και του ετερόπλευρου μαστού που λαμβάνουν ,[object Object],  υψηλές δόσεις.,[object Object],[object Object]
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