Practice Update: Oncology

EDITOR’S PICKS 6

Noninferiority of Partial-Breast and Reduced-Dose Radiotherapy After Breast Conservation Surgery for Patients With Early Breast Cancer The Lancet

Abstract BACKGROUND Local cancer relapse risk after breast conservation surgery fol- lowed by radiotherapy has fallen sharply in many countries, and is influenced by patient age and clinicopathological fac- tors. We hypothesise that partial-breast radiotherapy restricted to the vicinity of the original tumour in women at lower than average risk of local relapse will improve the balance of beneficial versus adverse effects compared with whole-breast radiotherapy. METHODS IMPORT LOW is a multicentre, ran- domised, controlled, phase 3, non-inferiority trial done in 30 radiotherapy centres in the UK. Women aged 50 years or older who had under- gone breast-conserving surgery for unifocal invasive ductal adenocarcinoma of grade 1-3, with a tumour size of 3 cm or less (pT1-2), none to three positive axillary nodes (pN0-1), and min- imum microscopic margins of non-cancerous margins, mostly hormone-positive (receiv- ing endocrine therapy) and node-negative (although the protocol allowed for N1 dis- ease, very few patients were enrolled). Although this study alone, with only 5 years of follow-up, may not convince radiation oncologists to change their current practice away from treating the whole breast in this population, it does offer supportive evidence that it is safe to block the medial left breast (when the tumor bed is not in that location) to avoid the heart. Additionally, although not directly addressed in this study, the low recurrence rate may also lend evidence to avoid boosting the lumpectomy cavity (as is common practice in the US) in this patient population.

Take-home message • This phase III noninferiority trial enrolled 2016 women who had undergone breast-conserving surgery for grade 1–3 unifocal invasive ductal adenocarcinoma. They were randomized 1:1:1 to receive 40 Gy whole-breast radiotherapy (control; n = 674), 36 Gy whole-breast radiotherapy and 40 Gy restricted to the vicinity of the original tumor (reduced-dose group; n = 673), or 40 Gy restricted to the vicinity of the original tumor only (partial-breast group; n = 669) to evaluate the balance of beneficial versus adverse effects among treatment groups. Compared with the control group, estimated 5-year differences in local relapse were −0.73% and −0.38% in the reduced-dose and partial-breast groups, respectively. Both the reduced-dose group and the partial-breast group exhibited noninferiority. Similar adverse events were reported among treatment groups, with significantly fewer reports of change in breast appearance (partial-breast group) and breast harder or firmer (partial-breast and reduced-dose groups). • These data demonstrate the noninferiority of reduced-dose and partial-breast radiotherapy compared with standard radiotherapy, approaches that can be imple- mented globally.

COMMENT By Noam VanderWalde MD

I n their impressive, phase III noninferi- ority trial, Coles et al randomized very early-stage breast cancer patients to one of three different techniques for adjuvant radiotherapy: 1) whole-breast radiotherapy using a hypofractionated technique (40 Gy in 15 fractions); 2) reduced dose of 36 Gy to the whole breast and an additional 40 Gy to the lumpec- tomy cavity (reduced-dose group); 3) 40 Gy in 15 fractions to the lumpectomy cav- ity (partial-breast group). All three groups were treated with forward planning field- in-field tangents, which is standard in most radiotherapy clinics. With 5 years of median follow-up, there were very few local recurrences (1.1% in the whole-breast group, 0.2% in the reduced-dose group, and 0.5% in the partial-breast group), and noninferiority for local recurrence was demonstrated among the three groups. Additionally, the results showed a statis- tically significantly lower patient-reported firmness of the breast in the reduced- dose and partial-breast groups, but no difference among the groups in any of the other adverse events. Many of late

adverse events, including heart, lung, and secondary cancers, occur so rarely that differences cannot realistically be demon- strated in a single study. This study is the first in what will likely be a number of studies to publish results comparing partial-breast radiotherapy to whole-breast radiotherapy (NSABP/RTOG, RAPID, SHARE, IRMA, etc), and the com- pilation of evidence will hopefully allow clinicians to make evidence-based deci- sions. What is unique about this study is that, as opposed to other partial-breast techniques that entail acceleration of tim- ing and other techniques of delivering radiotherapy (from one-dose intraoper- ative radiotherapy [IORT] to accelerated partial-breast irradiation [APBI] given over 1–2 weeks), this study only compared a change in one variable (ie, the volume of tissue being irradiated). The extremely low recurrence rate in all three groups and noninferiority demonstrate that it is at least safe to reduce the volume of tis- sue irradiated in this patient population (specifically very low-risk patients with unifocal non-lobular histology, >2 mm

Dr. VanderWalde is Assistant Professor,

Department of Radiation Oncology, University of Tennessee West Cancer Clinic.

PRACTICEUPDATE ONCOLOGY