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JOURNAL CLUB
Dr Bharti DevnaniModerator- Dr KP Haresh Date: 09-04-2016
Semin RadiatOncol26:51-58 2016
PMRT IN UPFRONT SETTING- EVIDENCE
Perez and Brady, Textbook of Radiation Oncology
PMRT IMPROVES OS - EBCTCG META-ANALYSIS
EBCTCG meta-analysis. Lancet 2005
PMRT IN NODE POSITIVE PATIENT
EBCTCG Meta-analysis Lancet 2014
PMRT IN NODE NEGATIVE PATIENT
EBCTCG Meta-analysis Lancet 2014
INDICATIONS OF PMRT ARE EXPANDING…..
Isolated local recurrence
Breast cancer mortality
Radiation is an important treatment post MRM
Standard indications of PMRT T4 Node positive disease Margin positive T3N0 with high risk features
No benefit in pN0 disease
Decision of PMRT is mainly based on histo-pathological findings
ROLE OF NACT
Targeting systemic and locoregional disease
Downstaging of disease
Breast conservation
In vivo assessment of sensitivity of chemotherapy
To tailor and limit subsequent locoregional treatment
Increasing pCR 10-15 % with anthracyclines 25-30% with anthracyclines/Taxane 40-50 % with chemo + transtuzumab in Her-
2+ 50-60% with chemo and 2 anti Her-2 agents
Decrease in rates of axillary positivity 30 % with anthracyclines Upto 40% with anthracyclines/Taxane > 50% with chemo and 2 anti Her-2 agents
NACT- ASSOCIATION OF PCR WITH EFS & OS
Cortazer et al. Lancet 2014; 384: 164–72
NACT COMPLICATES DECISION MAKING OF PMRT
Jungle of risk factors
Response to
systemic treatment
Biological features
pT0/pN0pN0/residual
BrpT+/pN+
CLINICALAge
T sizeN stageStage
How to tailor the treatment decision of
LRRT based on above risk factors ??
Semin RadiatOncol26:51-58 C 2016 Semin RadiatOncol26:51-58 2016
Department of Radiation Oncology, The Ohio State University, Columbus, OH.
OUTLINEPublished literature from MDACC Risk factors of LRF Impact of PMRT on std risk features post
NACT
Grey areaso Young ageo Stage II diseaseo pCR- ypN0
Ongoing trials and future perspectives
RETROSPECTIVE DATA FROM MDACC
MDACC PATIENTS POOL
Huang et al. IJROBP 2005;62:351-7
CLINICO-PATHOLOGICAL FACTORS PREDICTIVE OF LRF & IMPACT OF PMRT
Huang et al. IJROBP 2005;62:351-7
No RT group
RT group
T3-T4 56% 84%N2-N3 20% 43%N+ 52% 72%
Patient characteristics
LRR rate RT v/s no RT
22% vs 11%
SUBSET ANALYSISLRR who initially had stage III or IV & achieved pCR
33% vs 3%
Huang et al. IJROBP 2005;62:351-7
CAUSE SPECIFIC SURVIVALCSS for stage III and
IVCSS for > 4 nodes
positive
RISK FACTORS OF LRR
n =106
10years LRR irradiated v/s non irradiated --5% v/s 10%
McGuire et al. IJROBP 2007;68:1004-9
IMPORTANCE OF CLINICAL STAGE: PATIENTS WITH PCR
Not just the residual disease but the clinical extent of disease before treatment is also important
No RT-0/20 RT-0/10
No LRR events
Clinical Stage II disease Clinical Stage III disease
93 %
67 %
S
IMPORTANCE OF AGE <35 YEARS
Garg et al. IJROBP 2007;68:1478-83
Nagar et al. IJROBP 2011;81:782-7
4% vs 24% p<0.001
Nagar et al. IJROBP 2011;81:782-7
ypN+ ypN0
p <0.001 2% vs 14%p <0.06
RECOMMENDATION BASED ON MDACC STUDIESo Stage III diseaseo cN2-N3 involvemento Residual pathologically involved nodes(ypN
+)o CT3N0 pN+ disease post NACT
Role of PMRT for cT3N0 who remain yPN0 post NACT remains unclear
LIMITATIONS OF MDACC STUDIES Retrospective
Single institutional data
Non-randomised (Bias)
Follow up is relatively modest
PMRT IN WOMEN WITH PATHOLOGICAL NEGATIVE LYMPH NODE
NSABP B-18/B-27- COMBINED ANALYSIS
10 YR CUMULATIVE LRR RATES IN POST MRM PATIENTS <5 CM
Mamouns et al. J Clin Oncol 2012; 30:3960-3966
10 YR CUMULATIVE LRR RATES IN POST MRM PATIENTS >5 CM
NOMOGRAM FOR PREDICTION OF 10 YRS RATE OF LRR- POST MRM
10-year LRR-FS, 96.2% vs 86.8% p=0.18
n=13478 & 56
10-year OS, 77.2% vs 87.7% p=0.15
Scodan et al. IJROBP 2012;82:1-7
Omission of PMRT was notdetrimental in Stage II ,IIIpatients with negative lymph nodes after NAC and mastectomy
Shim et al . IJROBP 2013;88:65-72
Annals of Oncology 00: 1–10, 2016
Benefit of PMRT in cN1 patients irrespective of thepathologic lymph node response to NAC
NSABP B-51 TRIALn=1636
ALLIANCE TRIAL Can RT alone provide sufficient regional
control for patients with ypN + disease after NAC
Prognostic value is greatest in
aggressive tumor subtype
Triple Neg
HR neg Her-2 +
Cortazer et al. Lancet 2014; 384: 164–72
Yang et al. Ann Surg Oncol 2015 22:495–501
Poor responders to NAC with TN breast cancer represent a populationat high risk for LRR, and maximal locoregional therapy should be considered for these patients
Fowble et al. IJROBP 2012;83: 494-503
CONCLUSION PMRT after NACT is debatable. Based on retrospective data PMRT –post
NACT should be given in Clinical stage III (especially N2-N3) Residual disease (++ if yp+) High risk factors like young age, triple
negative Stage II and T3 N0……still grey area…
personalized decision Prospective randomized trials are required
IRCH PROTOCOL All patients planned for NACT (Clinical stage
decided by combined team and documented in file clearly)
All BCS patients to receive WBRT+Boost.
Decision for Adjuvant therapy based on initial clinical staging and decision
Pathological CR not to guide radiation therapy!!!
FUTURE PERSPECTIVESIntensification of treatment in poor respondersConcurrent chemotherapyAltered fractionationRadiosensitizers like PARP inhibitors (SWOG
1509)
Need of comprehensive nodal irradiation (in TN & Her 2 +)
S1509, “A Phase II Study of Veliparib Administered Concurrently with Radiotherapy for Inflammatory or High-Risk Triple-Negative Breast Cancer to A Phase II Randomized, Double-Blinded, Placebo-Controlled Trial of Veliparib Administered Concurrently with Radiotherapy for Inflammatory or High-Risk Triple-Negative Breast Cancer.” Dr. Jagsi.