Disclosure. Objectives 03/19/2019. Current Issues in Management of DCIS Radiation Oncology Considerations

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1 Current Issues in Management of DCIS Radiation Oncology Considerations Fariba Asrari, M.D. Director. Johns Hopkins Breast Center at Green Spring Station Department of Radiation Oncology & Molecular Sciences Johns Hopkins University School of Medicine Disclosure Objectives Clinical factors for Rad onc decision making Management & Literature Review Radiation Regimen Biological/Genomic factors Ongoing Trials, Future Direction 1

2 In-situ Breast Cancer 2017: 63,000 women in USA (>80% DCIS) 20-50% ( Significant uncertainty) will develop Invasive cancer 2018 AJCC 8 th edition LCIS classified as a benign entity & removed from TNM staging Is DCIS a precursor to Invasive ca? Half of DCIS recurrences are invasive. Similarities in morphology and genetic profiles between invasive & in situ cancers which indicates DCIS is a precursor to invasive ca 2

3 Current DCIS Management Lumpectomy + Radiation 40% Lumpectomy alone 30% Mastectomy 30% Jackson,et al Amer J Surg 2008 Ibrahim,et al JCO 2007 Smith,et al Int J Radiat Oncol, 2006 Is SLN Bx needed for DCIS? Should be done when mastectomy is chosen Maybe considered with significant risk of upstaging when pt wishes to avoid another surgery: - Large DCIS - Palpable mass Surgical Margins for DCIS Consensus For women undergoing Lumpectomy & Radiation, a negative margin width of at least 2 mm, as compared to a narrower negative margin, minimizes risk of local Recurrence Morrow,et al JCO

4 Factors to consider Important factors to be analyzed when determining whether or not to offer post lumpectomy radiation and/or hormonal therapy Comedo necrosis Margins (Ideally to be 2mm or more) Age Size of lesion Grade? ( not significant in NSABP trials, but significant in ECOG Trial) Does Age matter? Young age (<40 years) is associated with a higher risk of recurrence, especially invasive recurrence, following BCS. Older age (>80 years) is associated with a lower risk of any recurrence. Management Post-lumpectomy Radiation reduces the risk of local recurrence for DCIS by half. Endocrine therapy reduces the risk of local recurrence after Lumpectomy & Radiation by one third DCIS treatment should be individualized based on clinical, pathological features, patient preference & possibly Molecular profile No clear consensus for whom to omit radiation 4

5 Do all DCIS patients need Radiation?? No clear definition. Low Risk DCIS Ongoing COMET trial: low & intermediategrade without comedo necrosis, ER+or PR+, HER2-negative (if tested) Molecular profiles to be considered in any discussion of low-risk disease Breast cancer Mortality After DCIS diagnosis SEER data on pts with stage 0 : 108,196 pts Evaluated impact of second primary breast cancer on 20 year mortality 20 yr BC Specific Mortality: 3.3 % overall 7.8% vs 3.2% for women <35yo vs >35yo. Narod,et al,jama

6 Breast cancer specific mortality Risk factors for death from breast cancer - Age at diagnosis - Black ethnicity. The risk of death increases after a diagnosis of an ipsilateral second primary invasive breast cancer, but prevention of these recurrences by radiotherapy does not diminish breast cancer mortality at 10 years. Randomized Trials of Excision+/- RT NSABP B-17 EORTC SweDCIS UK/ANZ Lower Local Recurrence in Modern era Local recurrence rates following BCS have declined over time, likely because of improvements in radiologic detection, pathologic assessment and systemic treatment. 6

7 EORTC pts, DCIS 5 cm or less, Neg marg, Mostly mammo detected Median F/U: 15 y Randomized to Lumpectomy +/- 50Gy RT, No Boost Local Recurr 31% vs 18% in favor of RT No DFS, OS difference Julien,et al Lancet 2000 EBCTCG Meta-analysis 3729 pts in 4 randomized trials Local Recurr Rate: - Lumpectomy 28.1% - Lumpectomy +RT 12.9% Effective regardless of the age, extent of BCS, use of tamoxifen, method of DCIS detection, margin status, focality, grade, comedonecrosis or tumor size. Ommision of Radiation for DCIS tested: RTOG 9804 ECOG

8 RTOG 9804 for Good Risk DCIS Good risk DCIS: G1, G2, Margins 3mm or more 636 pts accrued of planned 1790 Median F/U : 7 Years Local Recurrence: Lumpectomy: 7% Lumpectomy+RT: 1% Statistically Significant benefit but small McCormick, et al JCO 2015 ECOG 5194 Prospective single arm study for lumpectomy without RT for DCIS, all with 3mm or more margin Median F/U: 12.3 y Cohorts Pts# LR(all) LR IDC G1-2, 2.5 cm or less 561 pts 14.4% 7.5% G3, 1cm or less: 104 pts 24.6% 13.4% Solin,et al JCO 2015 Is Hypofractionation for DCIS appropriate? Data Mainly Extrapolated from Invasive BC studies Published Small series with excellent local control for DCIS TROG 07.01: Ongoing Randomized trial for Conventional vs Hypofractionation & Boost vs No Boost for Non-low risk DCIS 8

9 Is Boost needed for DCIS? Boost for DCIS Is PBI appropriate for DCIS? Low Risk DCIS per 2016 ASTRO Guidelines is suitable if all following criteria is met: Screen detected DCIS G1-G2 Size 2.5 cm or less Surgical Margin of 3 mm or more 9

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11 DCISionRT Provides recurrence risk & predicts radiotherapy benefit for DCIS pts following Lumpectomy Bremer, et al clin cancer res 2018 A New Biologic Profile for DCIS Assesses critical pathways Integrates clinicopathologic factors Hormone Receptor HER2 Proliferation Stress Response Cell Cycle Clinicopathologic Factors PR HER2 Ki-67 COX-2 p16 AGE PALPABLE FOXA1 SIAH2 LESION EXTENT MARGIN STATUS 33 11

12 DCISionRT Changing Treatment Paradigm for DCIS Is Active Surveillance Appropriate for DCIS? Ongoing Trials LORD in Europe: Randomized, Multicenter, Noninferiority Trial, Between Standard Therapy Approach Versus Active Surveillance for Low Risk DCIS) LORIS in Europe : Phase III Trial of Surgery versus Active Surveillance for Low Risk DCIS COMET in USA: looking at the risks and benefits of active surveillance compared to guideline concordant care 12

13 Thank you for your attention 13