Radiotherapy after neo-adjuvant chemotherapy Lustrumcongres Moeilijke Mamma s 31 januari 2014 dr Paula Elkhuizen Radiotherapeut-oncoloog
Indications for neoadjuvant chemotherapy (NAC) - Patients with inflammatory breast cancer - Patients who might become eligible for BCT after NAC - Patients treated in trials investigating the effect of NAC Before start neo-adjuvant chemotherapy; consult radiotherapy
Pre-NAC consult; locally advanced; in all cases RT indication Infra/supraclaviculair; RT doses Huid betrokkenheid; RT opheffen huidsparing; bolus Uitbreiding huidlaesies; Aanpassing RT veld
Radiotherapy after neo-adjuvant chemotherapy RT indication (Patient factors) Pathological T stage pathological N stage Histological factors (lymfangio-invasion, grade etc) Which patients need RT?? After neo-adj CT (partly) unknown..
Indications for post-operative radiotherapy after neoadjuvant chemotherapy First serie 2002, IJRBOP Buchholz et al: MD Anderson 2 prospective trials (neo) adj CT and mastectomy 150 pts NAC and surgery NO RT based on yptnm 5 yr LRR 27% compared to 1031 pts surgery and adjuvant chemotherapy NO RT based on ptnm 5 yr LRR 15% p = 0.001
2002, IJRBOP Buchholz et al: MD Anderson For all path T size; LRR NEO was higher than LRR ADJ All ct3-t4 patients but 1, experienced a LRR > 4 nodes involved; Not only yptnm but also ctnm stage prior to chemotherapy is important!! higher LRR in NEO group (54% vs 23%) Subgroup (y)pt2n1-3 nodes positive: Higher LRR in NEO group 32% vs 8% in ADJ group
McGuire et al IJROBP 2007, n= 106 Patients with pcr after NAC and surgery Retrospective serie, RT (n= 72) and no RT (n=34) Clinical Stage I-II; RT no influence (10 yrs LRR 0%) Clin Stage III (T1-3N2-3) RT improves LRR 7.3% vs 33.3 % RT improves DFS and OS
Radiotherapy after NAC Indications RT: ct3-4; cn2-3 ypt3-4; ypn2-3 Also in case of complete response!! Problem: intermediate groep ct1-2n1 ypt1-2 N0-1
Radiotherapy after NAC -intermediate group- scarse literature NAC and LRR Conflicting results Most databases no NAC in case of operable breast carcinoma More recent NAC series; role of RT in case of N+ was known; (LR and OS) RT according to physician NSABP rule untill late 90 s: no regional lymphnode RT, no PMRT
N= 3088 Neo-adjuvant chemotherapy trials All patients NO radiotherapy >10 yrs Follow up ct1-3n0-1
Manoumas et al. 1e prospective serie N=3088 pt NSABP B-18; 1988-1993; n= 1523 ; med FU 15.4 yrs NSABP-27; 1995-2000; n= 2411; med FU 11.75 yrs Neo-adjuvant chemotherapy Disadvantage; cn clinically without ultrasound + cytology
Manoumas et al. 1e prospective serie N=3088 pt 10 yrs LRR after mastectomy 12.3%, 10 yrs LRR after BCT 10.3 % Risk factors for LRR BCT: age and cn; ypt and ypn mastectomy: ct and cn; ypt and ypn age not sign
ct <= 5 cm 10 yrs LRR after Mastectomy- no RT Most LRR in case of ypn+; especially when cn+ Especially when T3 ct > 5cm
>= 50 yrs < 50 yrs 10 yrs LRR after BCT with RT breast Most LRR in case of ypn+; especially when cn+ and Age <50 yrs
In the mean time: Rapchem RAdiotherapy after Primary CHEMo therapy Onduidelijkheid; veel onder- en overbehandeling Gerandomiseerde trial niet mogelijk binnen NL Registratie studie met behandel richtlijn; Uniformiteit binnen NL Registreren van gegevens
RAPCHEM (treatment guidelines) according to ypn status Group I: ypt1-2n0: LR risk < 10%» after MRM: no RT. Group II: ypt1-2n1: LRR risk 10-35%» after MRM: RT thoracic wall. Group III: ypt1-2n 2: high LRR risk» after MRM: RT thoracic wall and supraclavicular nodes. (RT axilla and IMS optional)
Rapchem Patients with ct1-2cn1 All radiotherapy institutes conform to these guidelines Started January 2011 N= 720
Rapchem Patients with ct1-2cn1 N1 status - cytologie/histologie - positieve SN Indien > 3 pathologische klieren axillair op echo/ MRI/ PET cn2 (4+); RT indicatie ongeacht respons Indien N1: ook echo periclav pre-chemo: klieren infra/supraclav + cn3; RT indicatie ongeacht respons
N1: Echo periclav? Pre-NAC consult; ct1-2n0-1 N+; aantal klieren ivm RAPCHEM; indien >= 3 klieren; cn2(4+); RT indicatie ongeacht respons Kans post-operatieve RT; evt reconstructie
RAPCHEM (treatment guidelines) according to ypn status Group I: ypt1-2n0: T2N0 met graad III of LVI T3N0» after MRM: no RT. Group II: ypt1-2n1: Neo Supremo no RT vs thoracic wall RT» after MRM: RT thoracic wall. Group III: ypt1-2n 2:» after MRM: RT thoracic wall and supraclavicular nodes. (RT axilla and IMS optional)
Low intermediate high / 19 Low-intermediate risk pts are upstaged to cn2(4+) and N3 (22%) ypn0; indication RT missed (9%) ypn1; regional lymph node area missed (6%) ypn2-3; RT given (PET upstage no influence) (7%) High Risk patients RT field adaption in 15 %
Radiotherapy after neo-adjuvant chemotherapy- conclusions Classical factors (ct, cn, grade, LVI) after NAC (partly) unknown RT indication ct3-4; cn2-3 RT indication ypt3-4; ypn2-3 also in case of pcr Before start neo-adjuvant chemotherapy; Intermediate group (ct1-2n1; ypt1-2 N0-1) RAPCHEM consult radiotherapy PET scan; changes local treatment in 15% of the pts
RAPCHEM RAdiotherapy after Primary CHEMo therapy Writing committee Radiotherapie: LJ Boersma, PHM Elkhuizen, P Poortmans Chirurgie T van Dalen Medische oncologie S Linn Pathologie J Wesseling Statistiek/methodologie A Voogd, R Houben
5 years LRR according to (y)pn stage Matched group 1 NEO with 2 ADJ No differences in age, ER, PR