Locally advanced BC: radiation therapy
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1 Locally advanced BC: radiation therapy Philip Poortmans, MD, PhD 16 September 2016 Past-President Department of Radiation Oncology
2 Conflict of interest: none
3 Locally advanced breast cancer: radiation therapy 1. Introduction 2. Current evidence 3. A technical radiation oncology note 4. How to proceed 5. Conclusions
4 Radiation therapy for LABC: introduction Definition: Locally advanced breast cancer is a subset of breast cancer characterized by the most advanced breast tumours in the absence of distant metastasis. NCCN AJCC stage III Tumours more than 5 cm in size with regional lymphadenopathy (N1 3) Tumours of any size with direct extension to the chest wall or skin, or both (including ulcer or satellite nodules), regardless of regional lymphadenopathy Presence of regional lymphadenopathy (clinically fixed or matted axillary lymph nodes, or any of infraclavicular, supraclavicular, or internal mammary lymphadenopathy) regardless of tumour stage Locally advanced breast cancer is further divided into resectable or non-resectable based on the probability of achieving negative margins on histopathologic examination after an initial surgical approach that would provide long-term reduction in locoregional recurrence. Garg PK, Prakash G. Curr Oncol. 2015;22:e
5 Therapeutic approach: High rate of locoregional and systemic failure despite the best efforts of surgeons to remove locoregional spread of the tumour in its entirety. Multimodality treatment is required: Surgery Radiation therapy for LABC: introduction Systemic therapy: chemotherapy; endocrine and targeted therapy ( ER/PR/HER2) Radiation therapy Possibly: combinations: radiochemotherapy (APBI) Sequence of systemic and locoregional therapy makes no difference in survival. Primary systemic therapy (PST) can improve the chances of R0 resection often preferred! Garg PK, Prakash G. Curr Oncol. 2015;22:e
6 Radiation therapy for LABC: introduction Therapeutic approach: High rate of locoregional and systemic failure despite the best efforts of surgeons to remove locoregional spread of the tumour in its entirety. Multimodality treatment is required: Surgery Systemic therapy: chemotherapy; endocrine and targeted therapy ( ER/PR/HER2) Radiation therapy Possibly: combinations: radiochemotherapy (APBI) Sequence of systemic and locoregional therapy makes no difference in survival. Primary systemic therapy (PST) can improve the chances of R0 resection often preferred! Garg PK, Prakash G. Curr Oncol. 2015;22:e
7 Therapeutic approach: High rate of locoregional and systemic failure despite the best efforts of surgeons to remove locoregional spread of the tumour in its entirety. Multimodality treatment is required: Surgery Radiation therapy for LABC: introduction Systemic therapy: chemotherapy; endocrine and targeted therapy ( ER/PR/HER2) Radiation therapy Possibly: combinations: radiochemotherapy (APBI) Sequence of systemic and locoregional therapy makes no difference in survival. Preoperative (or primary) systemic therapy (PST) can improve the chances of R0 resection often preferred! Garg PK, Prakash G. Curr Oncol. 2015;22:e
8 Locally advanced breast cancer: radiation therapy 1. Introduction 2. Current evidence 3. A technical radiation oncology note 4. How to proceed 5. Conclusions
9 Radiation therapy for LABC: current evidence
10 Radiation therapy for LABC: current evidence 6 studies (713 pts) PST + surgery ± RT Huang EH, et al. J Clin Oncol. 2004;22:
11 Radiation therapy for LABC: current evidence 226 pts PST pcr + surgery ± RT McGuire SE, et al. Int J Radiat Oncol Biol Phys. 2007;68:
12 Radiation therapy for LABC: interpretation NC/PD PR CR Triple -/Her2 type Lum B type Lum A type Poortmans P. Lancet Jun 21;383(9935):
13 Radiation therapy for LABC: interpretation Lum A; minor R NC/PD PR CR Triple -/Her2 type Lum B type Lum A type Poortmans P. Lancet Jun 21;383(9935):
14 Radiation therapy for LABC: interpretation ---; ypcr NC/PD PR CR Triple -/Her2 type Lum B type Lum A type Poortmans P. Lancet Jun 21;383(9935):
15 Radiation therapy for LABC: interpretation NC/PD PR CR ---; NC Triple -/Her2 type Lum B type Lum A type Poortmans P. Lancet Jun 21;383(9935):
16 Locally advanced breast cancer: radiation therapy 1. Introduction 2. Current evidence 3. A technical radiation oncology note 4. How to proceed 5. Conclusions
17 Radiation therapy for LABC: technical RT note Planning-CT-scan before and after PST March 2013: patient age 49 Tumour central in left breast: Biopsy (histology): IDA G3; triple FNA axillary LN: + FNA supraclavicular LN: + Conclusion after staging: ct3n3m0 Treatment: PST Referred for evaluation by RO TAC x 6
18 Radiation therapy for LABC: technical RT note Planning-CT-scan before and after PST May 2013: Major tumour regression on MRI Treatment: Continue TAC July 2013 MRM: ypt0ypn0 PMRT + boost on non-removed nodes
19 Radiation therapy for LABC: technical RT note Planning-CT-scan before and after PST March 2013 September 2013?
20 Radiation therapy for LABC: technical RT note Planning-CT-scan before and after PST March 2013 September 2013?
21 Radiation therapy for LABC: technical RT note Planning-CT-scan before and after PST March 2013 September 2013??!?!
22 Radiation therapy for LABC: technical RT note Planning-CT-scan before and after PST March 2013 September 2013? OK +!
23 Radiation therapy for LABC: technical RT note Planning-CT-scan before and after PST March 2013 September 2013 OK +?!?!
24 Radiation therapy for LABC: technical RT note Planning-CT-scan before and after PST March 2013 September 2013 OK
25 Radiation therapy for LABC: technical RT note Value of PET-CT for TV delineation Courtesy of MC Valli and A Fozza
26 Locally advanced breast cancer: radiation therapy 1. Introduction 2. Current evidence 3. A technical radiation oncology note 4. How to proceed 5. Conclusions
27 Radiation therapy for LABC: how to proceed In patients treated with preoperative systemic therapy, indications for radiation therapy and treatment fields should be based on the maximum stage from the pre-therapy clinical stage, pathologic stage, and tumor characteristics.
28 Radiation therapy for LABC: how to proceed Current prospective studies ACOSOG A ct1-t3 cn1pst surgery including SLNB If N+: ALND vs. RT
29 Radiation therapy for LABC: how to proceed Current prospective studies ACTO (Russia): ct0-t3cn+ PST mastectomy If N-: PMRT vs. observation
30 Radiation therapy for LABC: how to proceed Current prospective studies
31 Radiation therapy for LABC: how to proceed Indication for local RT in patients with ct1-2n1( less than 4 suspicious nodes on imaging) breast cancer, treated with primary systemic chemotherapy followed by surgery Chemotherapy yct0-2ycn0 yct0-2ycn 1 Breast surgery and SN Breast surgery and ALND ypt0-2yc/pn0 ypt0-2yc/pn 1 After ablatio mammae No thoracic wall RT thoracic wall RT After BCS RT breast +/- boost
32 Radiation therapy for LABC: how to proceed Indication for nodal RT in patients with ct1-2n1( less than 4 suspicious nodes on imaging) breast cancer, treated with primary systemic chemotherapy followed by surgery Chemotherapy yct0-2ycn0 yct0-2ycn 1 Breast surgery and SN Breast surgery and ALND Pre/post chemotherapy SLNB: micrometastases in 3 sentinel nodes, and no RF Pre/post chemotherapy SLNB: micrometastases in 3 sentinel nodes AND 1 RF, OR Pre/post chemotherapy SLNB: Macrometastases in 2 sentinel nodes and no RF, OR Prechemotherapy :palpable nodes or positive nodes on imaging ( PA proven) Pre/post chemotherapy SLNB: 2 macrometastases and 1 RF Prechemotherapy SLNB: 3 macromets; OR: 2 macro and 1 micromets; OR 1 macro- and 2 micrometastases. ypt3-4, any yc/pn No axillary RT Axillary RT level 1 and 2 Axillary RT level 1 and 2 AND periclav * RF = Risk factors on prechemo data: Grade 3, tumorsize > 3 cm, angioinvasion Periclav RT ; axillary RT level 1 and 2 according to institutional guidelines RT of Internal Mammary Chain acc to inst. Guidelines, or in case of positive SN in the IMC
33 Radiation therapy for LABC: how to proceed Future prospective studies Bollet MA, et al. Radiother Oncol 2012;102:82-88.
34 Radiation therapy for LABC: how to proceed Future prospective studies Bollet MA, et al. Radiother Oncol 2012;102:82-88.
35 Radiation therapy for LABC: how to proceed Future prospective studies Bollet MA, et al. Radiother Oncol 2012;102:82-88.
36 Radiation therapy for LABC: how to proceed Future prospective studies
37 So in the meantime
38 So in the meantime consensus agreements
39 1.Mastectomy for ct1-4; cn0 (US); no PST Protocol Radboud umc, March 2016.
40 Protocol Radboud umc, March BCT for ct1-3; cn0 (US); no PST
41 Protocol Radboud umc, March PST; cn0 (US +/- FNA)
42 3.2. PST; cn+(1-3) (US +/- FNA); MARI advised Protocol Radboud umc, March 2016.
43 Locally advanced breast cancer: radiation therapy 1. Introduction 2. Current evidence 3. A technical radiation oncology note 4. How to proceed 5. Conclusions
44 Radiation therapy for LABC: conclusions Initial staging, especially the LN, should guide the decision SLNB pre-pst = more info but relevance depends on protocol T3-T4 N2-N3 RT T1-T2 with pn0 after PST doubts
45 Radiation therapy for LABC: conclusions Tools to individualise: Pre-PST stage incl histology; VI; molecular profile; Response to PST Age Pre-PST consult by radiation oncologist including T-scan!!!!
46 Radiation therapy for LABC: conclusions Interaction systemic and locoregional treatments RT & survival: X Competition/interaction with surgery and systemic treatment risk for death < M+ importance of LC earlier stage BC improved systemic therapy also when stage IV?
47 An individualised case Case NJO Born in 1976 Menarche 13; G1P1A0 (28); premenopausal Nurse (home care), never smoked, family - Medical history: congenital cardiac valve insufficiency; scoliosis; urethral valves; volume left breast was always > right breast
48 An individualised case Case NJO (born 1976) Age = 30: lump left breast upper inner quadrant GP mammography/ultrasound: not suspect Planned follow up after 3 months: progression on ultrasound! : not suspicious 12 x 5 mm : 20 x 8 mm To be repeated in 3 months biopsy!
49 An individualised case Case NJO (born 1976) Lumpectomy: 1.8 cm IDA; G3; triple negative; R1 Re-excision &SN: no residual tumour; SN 1/1 ALND: 2+/12 (total 3/13) 2 nd opinion RT first Breast + boost (refused YBT) Regional RT then not indicated (2006)
50 An individualised case Case NJO (born 1976) August 2006, end of RT: LN supraclavicular! Back to place of 2 nd opinion CT-scan; PET-scan: (only) N+: Supraclavicular; aortic arch; subcarinal; infraclavicular/top axilla Error in reporting ~ specific anatomy Everything left side except suspicious upper mediastinal LN
51 An individualised case
52 An individualised case Case NJO (born 1976) At place of 2 nd opinion Dose-dense chemotherapy (AC) Clinical complete remission after 3 cycles No 6th cycle ~ toxicity: leucopoenia; anal fissure; abscess sphenoid sinus
53 An individualised case Case NJO (born 1976) Referred from place of 2 nd opinion for Consolidating 3D-CRT Gy/25 sessions on all PET + spots
54 An individualised case Second radiotherapy
55 An individualised case Second radiotherapy
56 An individualised case Combined plan (first + second)
57 An individualised case Combined plan (first + second)
58 An individualised case Combined plan (first + second)
59 An individualised case Combined plan (first + second)
60 An individualised case Case NJO (born 1976) Alternating FU with place of 2 nd opinion
61 An individualised case Case NJO (born 1976) Alternating FU with place of 2 nd opinion 3 years later: NED Free fat transplants to fill volume defect in PTB Pregnant prosperous delivery of a son!
62 An individualised case Case NJO (born 1976) Alternating FU with place of 2 nd opinion 3 years later: NED Free fat transplants to fill volume defect in PTB Pregnant prosperous delivery of a son! > 9 years later: NED
63 Radiation therapy for LABC: acknowledgements Angel Montero Luis Meritxell Arenas Prat Harry Bartelink Paula Elkhuizen Yazid Belkacemi
64
Philip Poortmans, MD, PhD
Past President President Elect Philip Poortmans, MD, PhD 2 To treat or not IMN: Balancing Risks and Benefits 3 Conflict of interest: I am a radiation oncologist 4 To treat or not to treat the IMN 1. Introduction
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