Background
Accelerated partial breast irradiation (APBI)
ELIOT [18] | GEC-ESTRO [14] | Livi et al. [21] | ||||||
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Technique | kV-IORT (INTRABEAM) | IOERT | Interstitial multicatheter brachytherapy | Intensity-modulated radiotherapy | ||||
Fractionation | 40–56 Gy WBI + 10–16 Gy boost | 1 × 20 Gy (+ EBRT in 15.2% of patients) | 50 Gy WBI + 10 Gy Boost | 1 × 21 Gy | 50 Gy WBI + 10 Gy Boost | - 8 × 4 Gy in 4 days (HDR) - 7 × 4.3 Gy in 4 days (HDR) - 50 Gy in 3–4 days (PDR) | 50 Gy WBI + 10 Gy Boost | 6 × 5 Gy in 2 weeks |
Inclusion criteria | Unifocal IDC, ≥ 45 years | 48–75 years, tumor size ≤ 2.5 cm | DCIS or pT1-2a (<3 cm) pN0/mi, margins ≥ 2 mm (≥5 mm for DCIS and ILC), no lymph-/hemangiosis, ≥ 40 years | Unifocal, ≤ 2.5 cm, > 40 years | ||||
Number of patients | 3451 | 1305 | 1184 | 520 | ||||
Recruitment period | 2000–2012 | 2000–2007 | 2004–2009 | 2005–2013 | ||||
Median follow up | 2.4 years | 5.8 years | 6.6 years | 5 years | ||||
Local recurrence at 5 years | 1.3% | 3.3% | 0.4% | 4.4% | 0.9% | 1.4% | 1.4% | 1.5% |
p = 0.042 (n.s.) HR n.a. |
p = 0.0001 HR 9.3 (95% CI 3.3–26.3) |
p = 0.42 HR n.a. |
p = 0.86 HR 1.16 (95% CI 0.2–5.8) | |||||
Overall survival at 5 years | 94.7% | 95.1% | 96.8% | 96.9% | 95.6% | 97.3% | 96.6% | 99.4% |
p = 0.099 HR n.a. |
p = 0.59 HR 1.1 (95% CI 0.7–1.9) |
p = 0.11 HR n.a. |
p = 0.057 HR 0.17 (95% CI 0.02–1.36) |
Multicatheter brachytherapy
Intraoperative radiotherapy (IORT)
External-beam radiotherapy
Conclusions of the DEGRO expert panel
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APBI is feasible and provides excellent results regarding toxicity and local control in selected low risk-patients.
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Although non-inferiority was established in the TARGIT A- and ELIOT-trial, there are some methodologic issues in the design of those trials including the additional use of EBRT, different timing in the IORT application and the choice of the non-inferiority margin.
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APBI using EBRT should be applied with caution until the results of phase III trials such as NSABP B-39/RTOG 0413, RAPID and IMPORT LOW are published.
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Multicatheter brachytherapy remains the only modality for which 10-year data are available.
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A meta-analysis including 4.489 patients from several of the above mentioned trials demonstrated that overall mortality is not increased with APBI [23].
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Long term follow up is needed to determine the impact of APBI on survival, the risk of late recurrences, adverse events as well as cosmetic results.
Radiotherapy of the lymphatic pathways in early stage breast cancer
Sentinel lymph node metastases
Conclusions of the DEGRO expert panel
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There is no clear standard for the treatment of patients with 1–2 sentinel lymph node metastases. It remains uncertain in which patients ALND and RNI including the axilla can safely be omitted.
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Since radiotherapy to the axilla and the SCN yields similar regional recurrence rate and survival compared to axillary dissection while the associated morbidity is reduced, it should always be considered when treatment of the axilla seems indicated.
Recent results on radiotherapy of the lymphatic pathways
MA.20 [10] | EORTC 22922/10925 [9] | DBCG-IMN [35] | French trial [36] | |||||
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Study design | Phase III randomized controlled trial | Phase III randomized controlled trial | Prospective cohort study | Phase III randomized controlled trial | ||||
Treatment arms | WBI + boost | WBI + boost + SCV/IMN | WBI + Boost TWI | WBI + boost + SCV/IMN TWI + SCV/IMN | WBI + Boost + SCV (left sided tumor location) | WBI + Boost + SCV/IMN (right sided tumor location) | TWI + SCV | TWI + SCV/IMN |
Inclusion criteria | N+ or N0 high risk (T3 or T2 with < 10 lymph resected lymph nodes and additional risk factors present) | N+ or N0 (medial or central tumor location) | N+ | N+ or N0 (medial or central tumor location) | ||||
Number of patients | 1832 | 4004 | 3089 | 1334 | ||||
Recruitment period | 2000–2007 | 1996–2004 | 2003–2007 | 1991–1997 | ||||
Median follow up | 9.5 years | 10.9 years | 8.9 years | 8.6 years | ||||
Disease-free survival | 77.0% | 82.0% | 69.1% | 72.1% | n.s. | 49.9% | 53.2% | |
p = 0.01; HR 0.76 (95% CI 0.61–0.94) |
p = 0.04; HR 0.89 (95% CI 0.80–1.00) |
p = 0.35 | ||||||
Overall survival | 81.8% | 82.8% | 80.7% | 82.3% | 72.2% | 75.9% | 59.3% | 62.6% |
p = 0.38; HR 0.91 (95%-CI 0.72–1.13) |
p = 0.06; HR 0.87 (95%-CI 0.76–1.00) |
p = 0.005; HR 0.82 (95%–CI 0.72–0.94) |
p = 0.8 |
Conclusions of the DEGRO expert panel
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RNI improves the outcome of patients with early stage breast cancer with locoregional lymph node involvement.
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In patients with 1–3 involved lymph nodes, RNI should be strongly considered, especially in the presence of further risk factors such as negative estrogen or progesterone receptor, poorly differentiated tumors, medial tumor location and premenopausal status.
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In patients with >3 involved lymph nodes, RNI should be regarded as mandatory.
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Irradiation of the IMN should be strongly considered in all patients in whom RNI is performed.
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Currently, due to the differing inclusion criteria for node negative patients in the MA.20- and the EORTC-trials, the optimal selection criteria for RNI in this subgroup remain unclear. However, it can be discussed on a case by case-basis in patients with the above-mentioned risk factors.
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Additional toxicity associated with RNI was mild and none of the mentioned trials showed an increase in cardiac morbidity or mortality, although further follow-up is necessary regarding this endpoint.
Ductal carcinoma in situ (DCIS)
Conclusions of the DEGRO expert panel
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Clinical and pathological factors can help to select patients at lower risk of local recurrence, however there is no uniform definition of a low risk-phenotype.
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Local recurrence rates show no plateau after 10 years of follow up in patients not undergoing radiotherapy.
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Radiotherapy significantly lowers ipsilateral invasive and non-invasive recurrences of DCIS after breast-conserving surgery.
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Patients with high-risk DCIS derive the highest absolute benefit from adjuvant radiotherapy.
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Although both invasive and non-invasive recurrences are significantly reduced by radiotherapy, there is no survival benefit.
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Patients should be informed about the beneficial effects and low toxicity of radiotherapy with optimal local control even in screening-detected DCIS.
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The rate of contralateral invasive breast cancer is considerably lower than the rate of ipsilateral local failure after radiotherapy, suggesting that radiotherapy could prevent secondary tumors.
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The role of boost radiotherapy and hypofractionation is currently unclear, however results from two prospective randomized controlled trials are pending.
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In clinical practice, individual risk factors as well as patient preferences, comorbidities and potential side effects should be carefully weighed against each other in the decision-making process concerning adjuvant radiotherapy.