波士顿——美国放射肿瘤学会(ASTRO)年会上报告的一项随机临床试验表明，与接受全乳腺照射(WBI)的女性相比，接受加速部分乳腺照射(APBI)者3年后的美容结果明显更差。

　　加拿大Juravinski癌症中心的Whelan博士报告称，根据护士的评价结果，在接受3D适形技术APBI治疗的女性中，近1/3(32%)的美容结果为“一般”或“差”；而在接受WBI治疗的女性中，仅有19%被评为“一般”或“差”。

　　同时，APBI比WBI伴随更多的1级或2级毒性。两组中3级毒性均少见，均未见4级毒性。“APBI组之所以毒性更大，可能与以下因素有关：3D适形技术的适形性有限，较短的照射间隔时间可能不合理(APBI单日照射2次，间隔6 h)，以及部分乳腺照射固有的不均匀性。”

　　便利换来毒性？

　　APBI仅对手术空洞进行外粒子束照射，每次照射采用较大剂量，从而得以在1周内完成治疗，便利性大大优于需要数周时间的多次分割放疗。然而，目前仍不清楚APBI是否要以更差的结局为代价来换取便利性。

　　为此，Whelan博士与来自加拿大、澳大利亚和新西兰的合作者开展了RAPID试验(3D适形外粒子束加速部分乳腺照射放疗的随机试验)，比较了这两种疗法对40岁以上侵袭性或非侵袭性乳腺癌(＜3 cm)女性患者的疗效和安全性。

　　研究者招募了2,135例患者，将其随机分组，一组给予WBI(n=1,065)，25次、50 Gy或16次、42.5 Gy，每日1次，进行或不进行增强照射；另一组给予3D适形APBI(n=1,070)，10次、38.5 Gy，每日2次。由经过培训的护士，采用欧洲癌症研究与治疗组织(EORTC)乳腺癌美容评分系统评价美容结果，采用国立癌症研究所不良事件常用术语标准3.0评价毒性。

　　放疗刚结束时，两组的美容结果相似，WBI组和APBI组分别有17%和19%的患者被评价为“一般”或“差”(P=0.35)。然而，针对850例可评估患者的3年(中位随访2.3年)中期分析显示，APBI组美容结果“一般”或“差”的患者比例比WBI组高出13%。

　　众说纷纭

　　新泽西癌症研究所放射肿瘤科主管Bruce Haffty博士评论指出：“RAPID试验的结果进一步揭示了加速部分乳腺照射的特性，凸显了进一步研究分割方案和将其与全乳腺照射进行比较的必要性。”

　　Whelan博士指出，5年时的组间差异与3年时相似，但并未提供具体数据。“支持部分乳腺照射的证据仍然不够充分，我们不仅一直缺乏有关其有效性的证据，而且现在又得到了有关其潜在毒性的证据。”

　　RAPID试验获得了加拿大健康研究所和加拿大乳腺癌研究联盟的支持。Whelan博士接受了阿斯利康和诺华提供的酬金。Haffty博士无利益冲突披露。

　　By: NEIL OSTERWEIL, Oncology Practice

　　BOSTON – Cosmetic results were significantly worse after 3 years for women who had accelerated partial-breast irradiation than for women treated with whole-breast irradiation in a randomized clinical trial, investigators found.

　　Nearly a third (32%) of women who underwent accelerated partial breast irradiation (APBI) with a 3-D conformal technique had cosmetic results rated as fair or poor by a nurse, compared with 19% of women who had undergone whole-breast irradiation (WBI), Dr. Timothy J. Whelan reported at the annual meeting of the American Society for Radiation Oncology.

　　APBI was also associated with more grade 1 and 2 toxicities than WBI, but there were few grade 3 toxicities with either technique and no grade 4 toxicities, said Dr. Whelan, a radiation oncologist at the Juravinski Cancer Centre in Hamilton, Ont.

　　"This increase in toxicity may have resulted from limited conformality of the 3-D conformal approach, the short time between the fractions – radiation with APBI was given twice a day with 6 hours between the fractions, which may not have been adequate – and maybe due to the asymmetric nature of partial breast irradiation itself, given that it’s only given to part of the breast," he said at a press briefing.

　　Trading Convenience for Toxicity?

　　APBI – in which a large dose per fraction of external beam radiation is given only to the surgical cavity with an additional safety margin – allows radiation therapy to be delivered in 1 week or less, making it an attractive alternative to multifraction therapy that can stretch over many weeks.

　　But it is still not clear whether APBI trades poorer outcomes for convenience, Dr. Whelan said. He and colleagues in Canada, Australia, and New Zealand conducted the RAPID Trial (Randomized Trial of Accelerated Partial-Breast Irradiation Using 3-D Conformal External Beam Radiation Therapy) to find out. The study compared the efficacy and safety of the two modalities in women over 40 years of age with invasive or noninvasive breast cancers smaller than 3 cm.

　　Investigators enrolled 2,135 patients and randomized them to receive either WBI (1,065 patients) at 50 Gy in 25 fractions or 42.5 Gy in 16 fractions given once daily with or without boost irradiation or 3-D conformal APBI at 38.5 Gy in 10 fractions twice daily (1,070 patients). Cosmetic results were rated by a trained nurse on a global assessment using the European Organisation for Research and Treatment of Cancer (EORTC) Cosmetic Rating System for Breast Cancer, and for toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0. Radiologists blinded to treatment type also rated results on digital photographs.

　　Immediately after radiation, cosmetic results were similar between the groups, with nurse-assessed appearance rated as fair or poor in 17% of women who had WBI, and 19% who had APBI (P = .35). However, an interim toxicity analysis among 850 evaluable patients, showed that at 3 years (2.3 years median follow-up) 13% more of the patients who had undergone APBI had fair or poor cosmesis.

　　The Jury Is Out

　　Dr. Whelan noted that the between-group differences were about the same at 5 years, but did not provide data.

　　"The evidence for partial-breast irradiation is still not very clear. We don’t have very robust evidence about its efficacy, and we just now have recent evidence about its potential toxicities, he said.

　　Dr. Bruce Haffty, chair of radiation oncology at the Cancer Institute of New Jersey in New Brunswick, commented that "the results from the RAPID trial shed further light on the use of accelerated partial-breast irradiation, and emphasize the need to further investigate these fractionation schemes and sort out whether in fact the toxicity from partial-breast irradiation may be slightly worse than with whole-breast irradiation."

　　Dr. Haffty moderated a briefing where the data were presented, but was not involved in the RAPID trial.

　　The RAPID trial is supported by the Canadian Institutes of Health Research and Canadian Breast Cancer Research Alliance. Dr. Whelan has received honoraria from AstraZeneca and Novartis. Dr. Haffty reported no relevant disclosures.