Internal Mammary Lymph Node Radiation: Pros and...
Transcript of Internal Mammary Lymph Node Radiation: Pros and...
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Internal Mammary Lymph Node Radiation: Pros and Cons of Inclusion In Radiation Fields
Jean Wright, MD
Johns Hopkins University
Department of Radiation Oncology
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NCIC MA.20
• Randomized trial of 1832 woman with node-positive breast cancer or “high risk” node-negative breast cancer – High risk = T>5 cm or – High risk – T2-5 cm, fewer than 10 nodes removed, and
either LVI, ER-, or grade 3
• Randomization: – Whole breast irradiation (WBI) vs – Whole breast irradiation plus regional nodal irradiation
(WBI + RNI)
• Followup: 9.5 years; primary endpoint: overall survival
Whelan et al, NEJM July 2015
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Survival Endpoints
Whelan et al, NEJM July 2015
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EORTC 22922
• Randomized trial of 4004 woman with node-positive breast cancer or node-negative breast cancer with medially located tumors
• Randomization:
– Whole breast (or chest wall) irradiation (WBI) vs
– Whole breast irradiation plus regional nodal irradiation (WBI + RNI)
• Followup: 10.9 years; Primary endpoint: overall survival
Poortmans et al, NEJM July 2015
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EORTC 22922 + MA.20
• Both studies suggest:
– Addition of RNI improved DFS and locoregional recurrence-free survival in a group of patients with primarily 1-3 positive nodes OR medially located tumors without positive nodes
• RNI in both studies specifically targets internal mammary nodes
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EORTC 22922 + MA.20: IM Coverage
MA.20
1st-3rd intercostal spaces
EORTC 22922
1st-5th intercostal spaces
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Hypotheses
• The addition of RNI impacts distant recurrence by treating microscopic nodal disease that may seed distant metastases, but never develop into clinically apparent regional recurrences
– This explains why treatment of the internal mammary nodes in medially located tumors impacts DFS even in axillary node-negative tumors
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So why not treat the internal mammary nodes?
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University of Michigan: Mean heart dose with internal mammary nodal radiation by treatment era
Mean Heart Dose (Left) “Early” 1997-2007
3D-CRT cohort
“Contemporary” 2014-2016
3D-CRT cohort
P-value
IMN RT 4.8 Gy 1.8 Gy <0.001
No IMN RT 2.6 Gy 1.1 Gy <0.001
Dess et al. Int J Radiat Oncol Biol Phys 2017
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Mean heart dose with internal mammary nodal radiation by treatment era
Mean Heart Dose “Early” 1997-2007
cohort
“Contemporary” 2014-2016
cohort
P-value
IMN RT 4.8 Gy 1.8 Gy <0.001
No IMN RT 2.6 Gy 1.1 Gy <0.001
Dess et al. Int J Radiat Oncol Biol Phys 2017
Coverage of internal mammary nodes increases
mean cardiac dose
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Radiation Impact On Cardiac Events is Dose Dependent
– Case-control study of 2168 women treated for breast cancer in Sweden and Denmark 1958-2001
• 963 with major coronary events (MCE)
• 1205 controls
– Radiation doses estimated based on “standard anatomy” as CT-based planning not done during this period
• Risk of MCE increases with cardiac dose
• No apparent threshold dose
Darby, NEJM 2013
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• While differences in mortality are detected late, coronary events may begin to occur earlier- providing an endpoint that is easier to study
Darby, NEJM 2013
Impact of Radiation Dose on Coronary Events
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Risk: 16.5% per Gy (almost identical to Darby et al within same
follow-up time)
Van den Bogaard J Clin Oncol 2017
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No cardiac risk
factors
Diabetes
Hypertension Prior ischemic
cardiac event
Excess risk of an acute coronary event (ACE) depends on mean V5 of the LV
Van den Bogaard J Clin Oncol 2017
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Why Not Treat IM?
• Benefit is likely to be small in most patients
• Generally confers increased cardiac exposure
• Must consider:
– Clinical benefit on case by case basis
– Ability to cover IM nodes while sparing the heart
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Impact of Respiratory Motion on Heart
Jagsi et al IJROBP 2007
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Deep Inspiration Breath Hold- Optimizing Anatomy
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Matched Electron-Photon Field for IM Coverage-
Using Modality to Optimize Dosimetry
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Partially Wide Photon Tangents for IM Coverage
Using Blocking to Shape Photon Field
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Protons for IM Coverage: Using Modality to Optimize Dosimetry
• RADCOMP: ongoing randomized trial of photons vs protons
• Primary Endpoint: Major Coronary Events
• Protons generally recommended on protocol, use off protocol may be increasing
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VMAT IMRT for Challenging Cardiac Anatomy
• The VMAT Trade-Off: – Improved dose
homogeneity
– Reduced high-dose volume outside contoured target
– At the cost of…
– Larger low-dose bath to heart and lung
• Offers dosimetric benefit in some challenging cases but not recommended routinely
Ho Radiat Oncol 2018
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FDG-avid on PET-CT
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Dose Constraints RTOG 1301
• Internal Mammary Nodes:
– Contour first 3 intercostal spaces, expand 5 mm in all dimensions except anterior and posterior
– 90% of the contoured IM should receive 45 Gy
• Heart (left sided)
– 20 Gy to <5% of the contoured heart
– 10 Gy to <30% of the contoured heart
– Mean dose <4 Gy
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Real- World Target Coverage of RTOG Volumes
• 20 actual cases re-planned with RTOG contours
• The mean V45 values for the RTOG consensus volumes: – CW 74% (SD 9%) – Ax3 96% (7%) – SCV 85% (10%) – IM 80% (21%) – Ax1 84% (19%) – Ax2 88% (17%)
Fontanilla PRO 2011
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Dosimetry
• Internal mammary node coverage goals on current protocols are higher than what has traditionally been achieved in the pre-contouring era
• Mean heart doses when the IM nodes are covered are often high enough to be clinically relevant
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Conclusions
• Benefit of IM radiation likely varies with individual characteristics, and may be very low in some node-positive patients
• Cardiotoxicity is an important consideration in selection of patients for regional nodal radiation
–Cardiac risk factors and anatomy should be considered for each patient individually
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Conclusions
• Judicious use of IM radiation in patients with established risk factors for recurrence with attention to cardiac risk may provide the best balance to reduce toxicity and improve disease-free survival outcomes
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Thank you!