美国圣约瑟慈善医院Frank A Vicini研究团队宣布他们探索了早期乳腺癌保乳术后加速部分乳房照射的长期结局。该项研究成果在线发表在2019年12月5日的《柳叶刀》上。
早期乳腺癌保乳术后全乳照射可降低同侧乳腺肿瘤复发率（IBTR），效果与乳腺切除术相当。目前尚不清楚部分乳腺加速照射（APBI）是否同样有效，该方案可缩短治疗时间。
2005年3月21日至2013年4月16日，研究组在美国、加拿大、爱尔兰和以色列的154个临床中心进行了一项随机、临床3期的等效性试验。共招募了4216名早期乳腺癌的成年女性，有肿块切除阴性手术边缘。根据疾病分期、绝经状态、激素受体状态和化疗意向等将这些患者分层，并按1：1随机分组，其中2109名接受全乳腺照射，2107名接受APBI。
中位随访10.2年后，APBI组2089名女性中有90名（4%）发生IBTR，全乳照射组2036名中有71名（3%）。APBI组10年累积IBTR的发生率为4.6%，全乳照射组为3.9%。两组中均有2%的患者死于复发性乳腺癌，且均未发生与治疗相关的死亡。
两组间二次肿瘤和治疗相关毒性的发生率相差不大。全乳照射组和APBI组中分别发生2020例和2089例不良事件。APBI组中发生1级毒性事件845例（40%）、2级921例（44%）、3级201例（10%）；全乳照射组中发生1级626例（31%）、2级1193例（59%）、3级143例（7%）。
结果表明，APBI不符合全乳照射在保乳治疗中控制IBTR等效性的标准。对于早期乳腺癌患者，研究组支持肿瘤切除术后进行全乳腺照射。但由于APBI的10年IBTR累积发病率略低于全乳照射，APBI亦不失为一种可接受的替代方案。
附：英文原文
Title: Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial
Author: Frank A Vicini, Reena S Cecchini, Julia R White, Douglas W Arthur, Thomas B Julian, Rachel A Rabinovitch, Robert R Kuske, Patricia A Ganz, David S Parda, Michael F Scheier, Kathryn A Winter, Soonmyung Paik, Henry M Kuerer, Laura A Vallow, Lori J Pierce, Eleftherios P Mamounas, Beryl McCormick, Joseph P Costantino, Harry D Bear, Isabelle Germain, Gregory Gustafson, Linda Grossheim, Ivy A Petersen, Richard S Hudes, Walter J Curran, John L Bryant, Norman Wolmark
Issue&Volume: December 05, 2019
Abstract:
Background
Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation.
Methods
We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intention-to-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and 1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov, NCT00103181.
Findings
Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10·2 years (IQR 7·5–11·5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1·22, 90% CI 0·94–1·58). The 10-year cumulative incidence of IBTR was 4·6% (95% CI 3·7–5·7) in the APBI group versus 3·9% (3·1–5·0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group.
Interpretation
APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women.
DOI: 10.1016/S0140-6736(19)32514-0
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32514-0/fulltext
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