波士頓——美國放射腫瘤學會(ASTRO)年會上報告的一項隨機臨床試驗表明，與接受全乳腺照射(WBI)的女性相比，接受加速部分乳腺照射(APBI)者3年後的美容結果明顯更差。

　　加拿大Juravinski癌症中心的Whelan博士報告稱，根據護士的評價結果，在接受3D適形技術APBI治療的女性中，近1/3(32%)的美容結果為“一般”或“差”；而在接受WBI治療的女性中，僅有19%被評為“一般”或“差”。

　　同時，APBI比WBI伴隨更多的1級或2級毒性。兩組中3級毒性均少見，均未見4級毒性。“APBI組之所以毒性更大，可能與以下因素有關：3D適形技術的適形性有限，較短的照射間隔時間可能不合理(APBI單日照射2次，間隔6 h)，以及部分乳腺照射固有的不均勻性。”

　　便利換來毒性？

　　APBI僅對手術空洞進行外粒子束照射，每次照射采用較大劑量，從而得以在1周內完成治療，便利性大大優於需要數周時間的多次分割放療。然而，目前仍不清楚APBI是否要以更差的結局為代價來換取便利性。

　　為此，Whelan博士與來自加拿大、澳大利亞和新西蘭的合作者開展了RAPID試驗(3D適形外粒子束加速部分乳腺照射放療的隨機試驗)，比較了這兩種療法對40歲以上侵襲性或非侵襲性乳腺癌(＜3 cm)女性患者的療效和安全性。

　　研究者招募了2,135例患者，將其隨機分組，一組給予WBI(n=1,065)，25次、50 Gy或16次、42.5 Gy，每日1次，進行或不進行增強照射；另一組給予3D適形APBI(n=1,070)，10次、38.5 Gy，每日2次。由經過培訓的護士，采用歐洲癌症研究與治療組織(EORTC)乳腺癌美容評分係統評價美容結果，采用國立癌症研究所不良事件常用術語標準3.0評價毒性。

　　放療剛結束時，兩組的美容結果相似，WBI組和APBI組分別有17%和19%的患者被評價為“一般”或“差”(P=0.35)。然而，針對850例可評估患者的3年(中位隨訪2.3年)中期分析顯示，APBI組美容結果“一般”或“差”的患者比例比WBI組高出13%。

　　眾說紛紜

　　新澤西癌症研究所放射腫瘤科主管Bruce Haffty博士評論指出：“RAPID試驗的結果進一步揭示了加速部分乳腺照射的特性，凸顯了進一步研究分割方案和將其與全乳腺照射進行比較的必要性。”

　　Whelan博士指出，5年時的組間差異與3年時相似，但並未提供具體數據。“支持部分乳腺照射的證據仍然不夠充分，我們不僅一直缺乏有關其有效性的證據，而且現在又得到了有關其潛在毒性的證據。”

　　RAPID試驗獲得了加拿大健康研究所和加拿大乳腺癌研究聯盟的支持。Whelan博士接受了阿斯利康和諾華提供的酬金。Haffty博士無利益衝突披露。

　　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.