Regional management of breast cancer - A Radiation Oncologist's perspective

1. Regional Management of Breast cancer
A Radiation Oncologist’s Perspective
DR. Ananda selvakumar Pandy. MD.DNB.FIPM.,
Senior Consultant
Department of Radiation Oncology & Clinical Research
Meenakshi Mission hospital & Research centre
Madurai

2. • Evolution & Evidence - RNI
• Consensus and Controversies
• Indications of RNI
• Techniques and Toxicities
• Take home messages to ur clinic !!
Overview

4. Evolution
• For years ALND was the standard of care
• In past decade, SLNB alone, SLNB + RT, Neoadjuvant
therapy have made it more difficult for radiation
oncologists to make decisions regarding management of
the axilla

5. Clinically node negative
disease
SLNB and what to do if the SLN is positive
In past, + SLN meant ALND but now there are other options for most
patients
For patients with 2 or fewer SLN+, studies exit for whole breast RT alone
(Z-11) or RNI (AMAROS)
Studies supporting RNI (MA20, EORTC 22922) shortly after Z-11 made RT
decisions difficult

6. Clinically node positive
disease
• These patients should undergo biopsy of positive LN to
confirm cancer involvement
• The only way to avoid ALND is with the use of
neoadjuvant chemotherapy

7. ALND Vs NO ALND

8. ACOSOG Z- 11

9. Warnings !!
• 46% of + SN were micromets
• Only 27% of patients undergoing ALND had additional LN
Many patients may have received “high tangents” (50%) and
19% had separate nodal field
• Radiation fields were not centrally reviewed
• Remember this is for BCT patients only
ACOSOG Z- 11

10. Confusing as this study comes out at the same time
others studies supporting regional nodal radiation.
Jagsi et al. 2014, JCO
ACOSOG Z- 11

11. Radiotherapy or surgery after a positive sentinel lymph
node with radiotherapy on this trial including the regional
lymphatics (at least axillary)

12. RT can be used in lieu of ALND with lower rates of
lymphedema
AMAROS

15. NCIC MA-20
RNI Improves outcome

17. • DMFS 75% no nodal RT v 78% nodal RT (p=0.02)
• DFS 69.1% no nodal RT v 72.1% nodal RT (p=0.04)
• OS 80.7% no nodal RT v 82.3% nodal RT (p=0.056)
• Comprehensive nodal RT improves outcomes

19. NO BENEFIT IN TZT ERA ??

20. • Recent data supports RNI for high risk patients with small benefits in
outcomes
• MA 20 and EORTC included SCV and IMN indicating that inclusion of
these nodes should be considered - Pre Transtuzumab era
• AMAROS indicates RT can be used in place of ALND with less
lymphedema
• Z-11 reported good outcomes for N+ patients undergoing BCT with WB
RT which includes some level 1/2 lymph nodes but not SCV or IMN. For this
study, a somewhat more favorable cohort & appropriate for more favorable
patients
Summary

21. PMRT/RNI after
Neo-adjuvant chemo

22. • Our recommendations are based on RCT based on
pathological information and absence of similar evidence for
these patients makes RT controversial
• Recent marked increased use of neoadjuvant chemotherapy
for patients with advanced disease, especially for Her-2-neu +
disease and Triple negative disease
• For radiation oncologists, this means loss of upfront
pathological evaluation to assist in determining the need for
PMRT or RNI

23. • For surgeons- axillary management ? Is SLN after chemo
enough? For clinical N0 pre- chemo? For clinical N+pre-chemo?
• For radiation oncologists ? Should we recommend PMRT
for SLN – after neoadjuvant chemo? For clinical N0 pre- chemo?
For clinical N+ pre-chemo?
• These remain challenging cases and at present off study
best to base on perceived stage at time of diagnosis using all
available information (CT chest, MRI, PET/CT, US)

24. Evaluation of axilla prior to
chemo ??
• In past, we would obtain SLN prior to neoadjuvant
chemotherapy
• At present, for clinically LN – patients we require
thorough clinical evaluation but do not require SLN upfront
for majority of patients & there is no consistency in the use
of pre-neoadjuvant chemo use of axillary US

25. NSABP B18 & B27
• This combined analysis looked at prognostic factors for LRR
• Preop AC from B18 and preop AC+/-T B27
• SLNB after chemotherapy
• pCR associated with lower rates of LRR
• Age, tumor size, clinical node status and conversion to pCR

26. • The overall 10-year LRR rate following NAC and mastectomy is
relatively low in the absence of PMRT, and have led some to suggest
omission of PMRT in patients with clinical stage II disease who
achieve a pCR.
• Patients enrolled in NSABP-18 and 27 were generally at far lower
risk of LRR overall than those in the retrospective studies
55% had cT1–2N0
20% had cT1–2N1
16% had cT3N0
and only 9% had cT3N1 disease.
Caution

27. Current trials

28. Hypo-fractionation in RNI

29. Axillary nodal irradiation
• No further axillary treatment is required after breast conservation surgery or
mastectomy if sentinel node shows isolated tumour cells or micrometastases.
• If the SN(s) shows macrometastases, further axillary treatment is no longer
mandatory for breast conservation patients receiving whole breast radiotherapy for
T1, Grade 1 or 2, ER+, HER2 negative and post-menopausal.
• If the SN(s) shows macrometastases, further axillary treatment should be
recommended for patients undergoing mastectomy or with tumours with one of the
following features: T3, Grade 3, ER- or HER2positive.

30. Axillary nodal irradiation
• For SN positive patients with macrometastases ( AMAROS eligible) ,axillary
radiotherapy is a reasonable alternative to further axillary surgery
• Radiotherapy can offered to patients where there is macroscopic disease
extending to the margins of axillary resection
• Axillary radiotherapy may also be considered in addition to surgery where
there are multiple positive nodes with extra capsular spread, or where there has
been sharp dissection of large nodes

31. Axillary nodal irradiation
• Radiotherapy to the axilla is not recommended in patients in whom a complete
microscopic clearance of the axillary nodes has been achieved.
• This is due to the increased risk of treatment associated morbidity with
radiotherapy over that seen with surgery

32. Internal mammary chain
irradiation
• Following analysis of EBCTCG meta-analysis of outcomes in women treated
with/without post-mastectomy loco regional radiotherapy including the
supraclavicular fossa, axilla and IMC ( 8% reduction on breast cancer mortality at
20 years in patients with 1-3 positive lymph nodes)
• MA20 and EORTC internal mammary- medial supraclavicular trials -disease free
survival benefit
• Danish internal mammary node study ( 3.7% overall survival benefit with increased
benefit in N2 disease, and N1 disease with central/medial tumour location.

33. Internal mammary chain
irradiation
• Internal mammary chain nodal radiotherapy can be considered in patients at high
risk of locoregional recurrence ( i.e. T4 and /or 4 or more axillary lymph node
macrometastases
• In patients with 1-3 axillary macrometastases, who have been recommended
locoregional irradiation, based on risk factors, inclusion of IMC in the target volume
should be considered if tumour location is central/medial
• Clinically Positive IMN nodes ( CT/MR/PET )
( Centres treating IMC should have breath- hold techniques. Wide tangents in
breath-hold or rotational therapies are capable of meeting constraints in the
majority of patients )

34. Supraclavicular irradiation
• Radiotherapy to the supraclavicular fossa is recommended in patients who have had
primary surgical treatment and are found to have ≥4 metastatic axillary lymph
nodes at pathological staging.
• With one to three positive lymph nodes in addition to other poor prognostic factors
e.g. T3 and/or histological grade 3 tumours, radiotherapy can be offered in patients
with good performance (as per NICE guidance)

35. Supraclavicular irradiation
After neo-adjuvant chemotherapy or hormone therapy:
• If axillary nodes are negative at presentation, and the nodal status is ypN-
after neo-adjuvant treatment, supraclavicular fossa radiotherapy is not
recommended.
• If axillary nodes are cytologically positive and/or clinically or radiologically
suspiciously enlarged at presentation, and if the nodal status is ypN- after neo-
adjuvant treatment, supraclavicular fossa radiotherapy should be considered.
• If the nodal status is ypN+ after neo-adjuvant treatment, supraclavicular fossa
radiotherapy is recommended.

36. • 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)
RTOG Volume coverage

37. MONO ISO TECHNIQUES

38. DIFFERENT ISO TECHNIQUES
Couch kick towards gantry

39. IMRT & VMAT
• • 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 spillage

42. • 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)
PROTONS

43. • 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)
PROTONS
More costly and not widely available !!

45. Shrinking Targets !!

46. RTOG Vs ESTRO Consensus on RT VOLUMES

47. Pre chemo & Pre surgery volumes !!