ALND. Dr. MJ Vrancken

ALND Dr. MJ Vrancken

ALND in primary surgery se1ng Axillary lymph node dissec8on (ALND) Very nice opera8on; dorsal approach 2

ALND in primary surgery se1ng Axillary lymph node dissec8on (ALND) Very nice opera8on; dorsal approach.. But, almost not performed anymore 3

Lymph nodes and breast cancer Provide for prognos8c informa8on to guide adjuvant systemic and regional treatment: surgery, radiotherapy, chemo/hormonal Rx Improved locoregional control Improved survival

Lymph nodes and breast cancer Provide for prognos8c informa8on to guide adjuvant systemic and regional treatment: surgery, radiotherapy, chemo/hormonal Rx Improved locoregional control Improved survival But..

Ques8on for you Lady, 45 yrs, self detected breast cancer lem breast, 1.5 cm, ER 90%, PgR 90%, Her2Neu neg, unifocal. Ultrasound axilla: normal nodes Who would advise breast conserva8on and SN procedure?

Ques8on for you Lady, 45 yrs, self detected breast cancer lem breast, 1.5 cm, ER 90%, PgR 90%, Her2Neu neg, unifocal. Ultrasound axilla: normal nodes Who would do intraopera8ve examina8on of the SN?

One more ques8on for you Histology: 16 mm gr 2 IDC, complete margins, Ki67 15%, SN meta 3 mm, 2nd node nega8ve Who would advice ALND?

One more ques8on for you Histology: 16 mm gr 2 IDC, complete margins, Ki67 15%, SN meta 3 mm, 2nd node nega8ve Who should advise radia8on treatment of the axilla?

One more ques8on for you Histology: 16 mm gr 2 IDC, complete margins, Ki67 15%, SN meta 3 mm, 2nd node nega8ve Who should advise wait and see?

ALND in primary surgery se1ng: NL BREAST CONSERVATION MASTECTOMY SLNB ALND SLNB ALND

Axillary staging Physical Examina8on Ultrasound ipsilateral axilla à FNA when suspect nodes Ultrasound periclavicular Nodes seen on mammography? Nodes seen on MRI? Addi8onal PET scan?

Management of the c N+ axilla Prof Maria Joao Cardoso

Management of the c N0 axilla SN procedure is standard of care The first lymph node on the direct drainage pathway from tumor 2nd tumor SN 3rd 2nd 3rd

Management of the c N0 axilla SN procedure is standard of care Pre-opera8ve injec8on with radioac8ve techne8um

Management of the c N0 axilla SN procedure is standard of care Peri-opera8ve patent blue

Management of the c N0 axilla : SN NSABP B32 trial; randomized phase III clinical trial No difference in OS, DFS or LRR in group of pa8ents that had SN alone compared to group of pa8ents that had SN + ALND cno pa:ents outcomes a@er 10 yr FU SLN + ALND n=1975 SLN only n=2011 Overall Survival (OS) 85.4 % 87.5 % Disease Free Survival (DFS) 77.0 % 76.4 % Local-regional recurrence 84 (4.3 %) 81 (4.0 %) Krag et al, Lancet 2010, Julian ASCO 2013

Management of the c N0 axilla : SN NSABP B32 trial; randomized phase III clinical trial Recurrences amer 10 yr FU cno pa:ents outcomes a@er 10 yr FU SLN + ALND n=1975 SLN only n=2011 Local recurrence 75 (3.8 % 66 (3.3 %) Axillary recurrence 3 (0.2 %) 9 (0.4%) Extra-axillary recurrence 6 (0.3 %) 6 (0.3 %) Weaver et al NEJM 2011, Julian ASCO 2013

Management of the c N0 axilla : neg SN Systemic review Iris vd Ploeg EJSO 2008 Studies 34 Pa8ents 14959 Occurrences (relaps) 67 à Risk 0.3 % Keep in mind =/- 7 % false posi8ve if backup ALND is done Recurrence amer ALND 0.8 2.35 % van der Ploeg IM, et al..eur J Surg Oncol. 2008.

Clinical Trials cn0 axilla : 1-2+ SLN TRIALS AMAROS (n=1425) OTOASAR (n=233) ACOSOG Z0011 (n=856) IBCSG 23-01 (n =933) AATRM (n=233) AxRT vs ALND 60 % macromets 68 % macromets observa:on vs ALND 50 % macromets micromets micromets Guiliano Ann Surg 2010, 2016; Donker M Lancet Oncol 2014; Galimber8 Lancet Oncol 2013; Sola Ann Surg Oncol 2013, Savolt EJSO 2017

Clinical Trials cn0 axilla 1-2+ SLN AMAROS AFTER MAPPING OF THE AXILLA: RADIOTHERAPY OF SURGERY 21

Clinical Trials cn0 axilla 1-2+ SLN cno à SN c ALND posi8ve Radia8on 22

Clinical Trials cn0 axilla 1-2+ SLN SN biopsy posi8ve AMAROS Donker et al, Lancet Oncol. 2014 nov; 1303 23

AMAROS : treatment compliance ALND (744 pts) AxRT (681 pts) Randomized treatment Both treatments Cross-over No axillary treatment 631 (84.8 %) 41 (5.5 %) 46 (6.2 %) 24 (3.2 %) 590 (86.6 %) 1 (0.1 %) 68 (10.0 %) 22 (3.2 %)

Clinical Trials cn0 axilla 1-2+ SLN AMAROS 25

AMAROS : results ALND (744 pts) Median number of all nodes removed (Q1-Q3) 15 (12-20) Number of addi8onal posi8ve nodes (besides SN) 0 1-3 4 67.1 % 25.0 % 7.8 %

AMAROS : results 5-years axillary recurrence rate: ALND 0.43% (4 / 744 events (0.54%)) AxRT 1.19% (7 / 681 events (1.03%)) << hypothesis (2%) Consequence: planned comparison is underpowered Donker et al, Lancet Oncol. 2014 nov; 1303 27

AMAROS : results Donker et al, Lancet Oncol. 2014 nov; 1303 28

AMAROS : lymphedema % 40 40.0% 29.8% 35 30 21.7% 28.0% 25 20 16.7% 13.6% ALND AxRT 15 10 5 P < 0.0001 P < 0.0001 P < 0.0001 0 1 3 5 Years amer randomiza8on 29

AMAROS : a liule sideway 3 groups of pa8ents: 1. no ultrasound of axilla performed 2. ultrasound performed; no suspect nodes 3. ultrasound performed; suspect nodes, FNA nega8ve

AMAROS : # pos SN per group

AMAROS : axillary recurrence per group

Conclusion of the AMAROS trial v Both ALND and ART provide excellent and comparable locoregional control in SN+ pa8ents v Significantly less lymphedema amer ART v ART can be considered standard or is a validated treatment for pa8ents with SN +ve

Clinical Trials cn0 axilla 1-2+ SLN SN biopsy posi8ve ACOSOG Z0011 34

Clinical Trials cn0 axilla 1-2+ SLN ACOSOG Z0011

Clinical Trials cn0 axilla 1-2+ SLN ACOSOG Z0011 Giuliano AE, et al. Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial. Ann Surg. 2016 Ø The cumulative incidence of nodal recurrences at 10 years: 0.5% in the ALND arm and 1.5% in the SLND alone arm (P = 0.28) Ø Ten-year cumulative locoregional recurrence was 6.2% with ALND and 5.3% with SLND alone (P = 0.36).

Clinical Trials cn0 axilla 1-2+ SLN Lancet Oncol. 2013 April ; 14(4): 297 305. doi:10.1016/s1470-2045(13)70035-4. IBCSG 23-01 IBCSG 23-01 randomised controlled trial comparing axillary dissection versus no axillary dissection in patients with sentinel node micrometastases Viviana Galimberti, MD 1, Bernard F. Cole, PhD 2,3, Stefano Zurrida, MD 4, Giuseppe Viale,

Clinical Trials cn0 axilla 1-2+ SLN Disease free survival IBCSG 23-01 No ALND ALND

Clinical Trials cn0 axilla 1-2+ SLN Addi:onal pos nodes in ALND Z0011 AMAROS OTOASOR IBCSG 23-01 AATRM 27.3 % 32.8 % 38. % 13 % 13 % Axillary recurrence; ALND 0.5 % 0.4 % 2 % 0.2 % 1.0 % other tx 1.1 % 1.2 % 1.7 % 1 % 1.7 % Median FU 9.25 yrs 6.1 yrs 8 yrs 5 yrs 5.1 yrs BCT 100 % 83 % 84 % 91 % 88 % v No difference in axillary recurrence rates between ALND and other treatment (observa8on or AxRT) and Guiliano Ann Surg 2010, 2016; Donker M Lancet Oncol 2014; Galimber8 Lancet Oncol 2013; Sola Ann Surg Oncol 2013, Savolt EJSO 2017

Clinical Trials cn0 axilla 1-2+ SLN Addi:onal pos nodes in ALND Z0011 AMAROS OTOASOR IBCSG 23-01 AATRM 27.3 % 32.8 % 38. % 13 % 13 % Axillary recurrence; ALND 0.5 % 0.4 % 2 % 0.2 % 1.0 % other tx 1.1 % 1.2 % 1.7 % 1 % 1.7 % Median FU 9.25 yrs 6.1 yrs 8 yrs 5 yrs 5.1 yrs BCT 100 % 83 % 84 % 91 % 88 % v No difference in axillary recurrence rates between ALND and other treatment (observa8on or AxRT) and v No difference in DFS or OS v Lower rates of lymphedema Guiliano Ann Surg 2010, 2016; Donker M Lancet Oncol 2014; Galimber8 Lancet Oncol 2013; Sola Ann Surg Oncol 2013, Savolt EJSO 2017

cn0 pa8ents that undergo BCT v Breast cancer pa8ents with cno disease and one or two tumor-posi8ve SLNs can be safely treated with breast conserving surgery and radiotherapy without performing ALND. à Therefore, intra-opera8ve assessment of SLNs should not be performed in these pa8ents.

cn0 pa8ents that undergo mastectomy EBCTCG overview sees advantage for post mastectomy RT in pa8ents with 1-3 posi8ve lymph nodes: beuer locoregional control and breast cancer related survival Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials EBCTCG (Early Breast Cancer Trialists Collaborative Group)* Summary EBCTCG, Lancet 2014 Jun 21

cn0 pa8ents that undergo mastectomy EBCTCG overview sees advantage for post mastectomy RT in pa8ents with 1-3 posi8ve lymph nodes: beuer locoregional control and breast cancer related survival A Locoregional recurrence first 100 1133 pn1 3 women with Mast+AD and systemic therapy 100 B Any first recurrence 100 C Breast cancer mortality Locoregional recurrence first (%) 90 80 70 60 50 40 30 20 log-rank 2p<0 00001 17 4 No RT 21 0% 10 3 2 RT 4 3% 0 0 5 10 15 20 Years Any first recurrence (%) 90 80 70 60 50 40 30 20 10 0 10-year gain 11 7% (SE 3 2) RR 0 67 (95% CI 0 55 0 82) log-rank 2p=0 00009 35 6 23 9 No RT 45 5% RT 33 8% 0 5 10 15 20 Years Breast cancer mortality (%) 90 80 70 60 50 40 30 20 10 0 20-year gain 7 9% (SE 3 3) RR 0 78 (95% CI 0 64 0 94) log-rank 2p=0 01 22 5 16 8 36 1 30 5 46 8 37 1 No RT 49 4% RT 41 5% 0 5 10 15 20 Years Figure 5: Effect of radiotherapy (RT) after mastectomy and axillary dissection (Mast+AD) on 10-year risks of locoregional and overall recurrence and on 20-year risk of breast cancer mortality in 1133 women with one to three pathologically positive nodes (pn1 3) in trials in which systemic therapy was given to both randomised treatment groups Analyses of locoregional recurrence first ignore distant recurrences, see appendix pp 8 9 for details. See appendix p 22 for analyses of both locoregional and distant recurrences, and appendix p 21 for analyses of overall mortality. RR=rate ratio. Vertical lines indicate 1 SE above or below the 5, 10, 15, and 20 year percentages. EBCTCG, Lancet 2014 Jun 21

cn0 pa8ents that undergo mastectomy Posi8ve SN & mastectomy in cn0 in NKI-AvL Ø First do mastectomy (incl. reconstruc8on if desired) and SN Ø then full pathology and discuss in MDM what to do: wait & see, PMRT ALND (+/- PMRT!) Ø The pa8ent has the opportunity of a shared decision

Axillary management cn0: where are we? NO axillary lymph node treatment: SN ve SN itc SN micrometa <2 mm if systemic adjuvant treatments is given SN macrometa, limited involvement, favourable tumor characteris8cs, incl. adj syst Rx & Whole Breast Irradia8on (Z-011 criteria)

Axillary management cn0: where are we? NO axillary lymph node treatment: SN ve SN itc SN micrometa <2 mm if systemic adjuvant treatments is given SN macrometa, limited involvement, favourable tumor characteris8cs, incl. adj syst Rx & Whole Breast Irradia8on (Z-011 criteria) Radiotherapy to the axilla (usually high tangents will do): SN macrometa high risk (mul8ple, larger primary)

Axillary management cn0: where are we? NO axillary lymph node treatment: SN ve SN itc SN micrometa <2 mm if systemic adjuvant treatments is given SN macrometa, limited involvement, favourable tumorcharacteris8cs, incl. adj syst Rx & Whole Breast Irradia8on (Z-011 criteria) Lymph node treatment (ALND): In some pts with residual macro metastases amer upfront therapy Pa8ents undergoing a mastectomy with SN involvement where there is no indica8on for post mastectomy RT

Axillary management cn0: where are we?

Axillary management cn0 ; SN + 77%

Axillary management cn0 ; SN + 86%

Axillary management cn0 ; SN + 84%

The fate of the ALND ; NKI-AvL data 100% ALND & BCT 90% 80% 70% 60% 50% 40% niet gedaan gedaan 30% 20% 10% 0% 1977 1980 1983 1986 1989 1992 1995 1998 2001 2004 2007 2010 2013 2016

The fate of the ALND ; NKI-AvL data 500 450 ALND & BCT: absolute nrs 400 350 300 250 200 gedaan niet gedaan 150 100 50 0 1977 1980 1983 1986 1989 1992 1995 1998 2001 2004 2007 2010 2013 2016

The fate of the ALND ; NKI-AvL data 100% ALND & mastectomy 90% 80% 70% 60% 50% 40% niet gedaan gedaan 30% 20% 10% 0% 1977 1980 1983 1986 1989 1992 1995 1998 2001 2004 2007 2010 2013 2016

The fate of the ALND ; NKI-AvL data 350 ALND & Mastectomy: absolute nrs 300 250 200 150 gedaan niet gedaan 100 50 0 1977 1980 1983 1986 1989 1992 1995 1998 2001 2004 2007 2010 2013 2016

Clinical Trials cn0 axilla : role SN BOOG 08 N=822 in both arms 56

Clinical Trials cn0 axilla : role SN Ongoing clinical trials: SLN biopsy vs axillary observation in patients with normal axillary US SOUND trial (NCT02167490): T<2cm BCT, planned 1560 pts INSEMA trial (NCT02466737): T<5cm, planned 5940 pts

Clinical Trials cn0 axilla : role SN

LANCET AUGUST 2017 If you want to read it all