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  • Dec 20, 2019
    APBI non-inferior to whole breast irradiation -- late toxicity and poor cosmesis more likely after APBI

    This paper reports on a randomized controlled trial of women >40 years old with DCIS or N0 breast cancer treated with lumpectomy and randomized to external beam APBI (38.5Gy/10fx BID) or whole breast RT (WBI)(45.4/16fx or 50Gy/25fx). Primary outcomes were ipsilateral breast tumor recurrence (IBTR). 2135 women enrolled with median follow-up of 8.6 years. 8-year cumulative rates of IBTR were 3.0% with APBI and 2.8% with WBI, not significantly different. Acute >grade 2 toxicity occurred in 28% in APBI and 45% in WBI (p<0.0001). Late >grade 2 toxicity was 32% in APBI and 13% in WBI (p<0.0001). Adverse cosmesis was more common after APBI at 3 years (absolute difference 11.3%), 5 years (16.5%) and 7 years (17.7%). Overall, APBI had non-inferior IBTR compared to WBI. Although there was less acute toxicity with APBI, there was increased late toxicity as well as adverse cosmesis (potentially related to the BID fractionation schedule). 

    Reference (PubMed Link): Whelan TJ, Julian JA, Berrang TS, et al. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (rapid): A randomised controlled trial. Lancet 2019;394:2165-2172.

    Key Institution: Multi-Institution (Canada, Australia, NZ)
    Keywords: Breast cancer, APBI, whole breast irradiation

  • Dec 14, 2019
    10-year follow-up of post-lumpectomy APBI vs whole-breast radiotherapy: NSABP B-39/RTOG 0413

    Breast-conserving surgery (lumpectomy) is a surgical oncologic resection where a localized, early stage, breast cancer is removed with a limited amount of surrounding tissue. This technique requires the supplementation of post-operative whole-breast radiation to reduce the risk of local recurrence. This was previously established to be equivalent to a modified radical mastectomy from a recurrence standpoint but spares the extensive morbidity and aesthetic changes associated with the surgery. Recently, efforts have been made to reduce both the quantity of normal breast exposed to radiation as well as the duration of the course in the adjuvant setting. Now resulting are the outcomes from a phase III randomized trial comparing whole-breast irradiation (WBI) to accelerated partial breast irradiation (APBI). Eligible patients were adult women with early stage (up to 3 positive lymph nodes) breast cancer who underwent lumpectomy with negative surgical margins. WBI was delivered to 50 Gy in 25 daily fractions with a supplemental tumor bed boost as decided by the treating clinicians. APBI was administered with either external-beam radiation to 38.5 Gy in 10 fractions over 5 treatment days or with brachytherapy to 34 Gy. Randomization stratification occurred according to stage, menopausal and hormone-receptor status as well as intention to receive chemotherapy. The primary outcome of in-breast tumor recurrence was analyzed in the intention-to-treat population. With a total of 4216 women enrolled across both arms, it was found that APBI did not meet the statistical criteria for equivalence to WBI with respect to the primary outcome of local recurrence. However, the weight of the clinical relevance of this result is controversial given it constituted an absolute difference of less than 1% in the 10-year cumulative incidence of local recurrence between the groups. Therefore, although strictly speaking APBI has a statistically significant increase in local recurrence, the value of this increase is minimal (< 1%) and may clinically permit its use in some women as an acceptable and more convenient regimen with similar toxicity profile per this trial. 

    Reference (PubMed Link): Vicini FA, Cecchini RS, White JR, et al. Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: A randomised, phase 3, equivalence trial. Lancet 2019;394:2155-2164.

    Key Institution: NRG Oncology
    Keywords: accelerated partial breast irradiation (APBI), whole-breast RT, early-stage breast cancer, breast conserving surgery 

  • Nov 20, 2019
    Lumpectomy plus partial breast reirradiation may be good alternative to mastectomy for recurrent breast cancer

    This multicenter, single-arm, prospective phase 2 trial assessed the effectiveness and safety of partial breast reirradiation after a second lumpectomy, to determine if it is an acceptable alternative to mastectomy. A total of 65 patients with ipsilateral recurrence after a second lumpectomy were enrolled, with the treatment of 3-dimentional conformal external beam partial breast reirradiation. Median follow-up was 5.5 years. The radiation dose was 1.5 Gy twice daily for 30 fractions. 58 patients were evaluable for the study, and 4 patients had breast cancer recurrence with 5-year cumulative incidence of 5%. Both distant-metastasis-free survival and overall survival rates were 95%. 4 patients (7%) had grade 3 toxicity and none had grade 4 toxicity. This study concluded that second breast conservation is an effective alternative to mastectomy.   

    Reference (PubMed Link): Arthur DW, Winter KA, Kuerer HM, et al. Effectiveness of breast-conserving surgery and 3-dimensional conformal partial breast reirradiation for recurrence of breast cancer in the ipsilateral breast: The nrg oncology/rtog 1014 phase 2 clinical trial. JAMA Oncol 2019.

    Key Institution:  Multi-Institutional (USA)
    Keywords: Partial breast reirradiation, breast cancer, recurrence, second lumpectomy 

  • Nov 20, 2019
    15-fraction radiation of chest wall and nodes not inferior to 25-fraction treatment

    This study addressed an important question of the efficacy of hypofractionated radiotherapy in postmastectomy patients. 820 patients with primary T3-4 disease or at least 4 positive axillary LNs were randomized to receive 50 Gy in 25 fractions over 5 weeks or 43.5 Gy in 15 fractions over 3 weeks. The primary endpoint was 5-year locoregional recurrence, and 5% margin was used to establish non-inferiority design. The median follow-up was 58.5 months. The 5-year cumulative incidence of locoregional recurrence was 8.3% (hypofractionation) vs 8.1% (conventional fractionation), with p < 0.0001 for non-inferiority. Patients receiving hypofractionated radiotherapy had higher chance of grade 3 acute skin toxicity (8%) than those receiving conventional radiotherapy. This study concluded that postmastectomy hypofractionated radiotherapy was non-inferior to conventional fractionated radiotherapy with similar toxicity profile.

    Reference (PubMed Link): Wang SL, Fang H, Song YW, et al. Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: A randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol 2019;20:352-360.

    Key Institution: Chinese Academy of Medical Sciences and Peking Union Medical College
    Keywords: Postmastectomy radiotherapy, hypofractionation, high-risk breast cancer, locoregional recurrence 

  • Oct 20, 2019
    Low long-term toxicity for proton RT for breast plus nodes treatment

    Regional nodal irradiation (RNI) is often recommended for patients following surgery for breast cancer who have risk factors for regional relapse. RNI often includes the internal mammary nodes (IMNs). However, treating the IMNs with radiotherapy increases the dose to the heart and lungs and may increase the long-term risk of toxicity. Proton beam radiation therapy may be able to spare cardiopulmonary radiation exposure although previously there had been no prospective studies showing a benefit.

    In the present study, 70 patients completed proton beam radiation including RNI coverage between 2011 and 2016. 91% of these patients had left-sided breast cancers and 94% had stage II or stage III disease. 99% received chemotherapy. On assessment of radiation delivery, the authors found that the median dose to the chest wall/breast was 49.7 Gy and 48.8 Gy to the IMNs. For the 62 surviving patients, the 5-year rates for locoregional relapse and overall survival were 1.5% and 91%, respectively. Only one patient developed grade 2 radiation pneumonitis and no patients developed grade 3 or higher pneumonitis. No grade 4 or higher toxicities occurred. There was no evidence of changes in echocardiograms or cardiac biomarkers.

    In conclusion, proton beam radiation therapy for breast cancer including RNI coverage was associated with low toxicity and comparable survival outcomes compared to what would be expected in terms of historical data.

    Randomized studies are needed to directly compare protons vs photons, but these are encouraging preliminary findings.

    Reference (PubMed Link): Jimenez RB, Hickey S, DePauw N, et al. Phase ii study of proton beam radiation therapy for patients with breast cancer requiring regional nodal irradiation. J Clin Oncol 2019;37:2778-2785.

    Key Institution: Massachusetts General Hospital
    Keywords: Proton therapy, breast cancer, regional nodal irradiation