Reddy Jay P, Lei Xiudong, Bloom Elizabeth S, Reed Valerie K, Schlembach Pamela J, Arzu Isidora, Mayo Lauren, Chun Stephen G, Ahmad Neelofur R, Stauder Michael C, Gopal Ramesh, Kaiser Kels, Fang Penny, Smith Benjamin D
Departments of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
Departments of Health Services Research, University of Texas MD Anderson Cancer Center, Houston, Texas.
Int J Radiat Oncol Biol Phys. 2023 Mar 1;115(3):629-644. doi: 10.1016/j.ijrobp.2022.09.083. Epub 2022 Oct 8.
Evidence supports use of partial-breast irradiation (PBI) in the management of early breast cancer, but the optimal dose-fractionation remains unsettled.
We conducted a phase 2 clinical trial (OPAL trial) to evaluate a novel PBI dosing schedule of 35 Gy in 10 daily fractions. Patients with close (<2 mm) margins also received a boost of 9 Gy in 3 fractions. Eligible patients underwent margin-negative lumpectomy for ductal carcinoma in situ or estrogen receptor-positive invasive breast cancer, up to 3 cm, pTis-T2 N0. The primary outcome was any grade ≥2 toxic effect occurring from the start of radiation through 6 months of follow-up. Secondary outcomes included patient-reported cosmesis, breast pain, and functional status, measured using the Breast Cancer Treatment Outcomes Scale, and physician-reported cosmesis, measured using the Radiation Therapy and Oncology Group scale. The Cochran-Armitage trend test and multivariable mixed-effects longitudinal growth curve models compared outcomes for the OPAL study population with those for a control group of similar patients treated with whole-breast irradiation (WBI) plus boost.
All 149 patients enrolled on the OPAL trial received the prescribed dose, and 17.4% received boost. The median age was 64 years; 83.2% were White, and 73.8% were overweight or obese. With median follow-up of 2.0 years, 1 patient (0.7%) experienced in-breast recurrence. Prevalence of the primary toxicity outcome was 17.4% (26 of 149 patients) in the OPAL trial compared with 72.7% (128 of 176 patients) in the control WBI-plus-boost cohort (P < .001). In longitudinal multivariable analysis, treatment on the OPAL trial was associated with improved patient-reported cosmesis (P < .001), functional status (P = .004), breast pain (P = .004), and physician-reported cosmesis (P < .001).
Treatment with daily PBI was associated with substantial reduction in early toxicity and improved patient- and physician-reported outcomes compared with WBI plus boost. Daily external-beam partial-breast irradiation with 13 or fewer fractions merits further prospective evaluation.
有证据支持在早期乳腺癌治疗中使用部分乳腺照射（PBI），但最佳剂量分割方案仍未确定。
我们开展了一项2期临床试验（OPAL试验），以评估一种新的PBI给药方案，即10次每日分割照射共35 Gy。切缘接近（<2 mm）的患者还接受了3次分割照射共9 Gy的追加剂量照射。符合条件的患者接受了切缘阴性的肿块切除术，用于原位导管癌或雌激素受体阳性浸润性乳腺癌，肿瘤大小达3 cm，pTis-T2 N0。主要结局是从放疗开始至随访6个月期间出现的任何≥2级毒性效应。次要结局包括患者报告的美容效果、乳房疼痛和功能状态（使用乳腺癌治疗结局量表进行测量），以及医生报告的美容效果（使用放射治疗肿瘤学组量表进行测量）。 Cochr an-Armitage趋势检验和多变量混合效应纵向生长曲线模型将OPAL研究人群的结局与接受全乳照射（WBI）加追加剂量照射的类似患者对照组的结局进行了比较。
OPAL试验纳入的所有149例患者均接受了规定剂量的照射，17.4%的患者接受了追加剂量照射。中位年龄为64岁；83.2%为白人，73.8%超重或肥胖。中位随访2.0年，1例患者（0.7%）出现乳腺内复发。OPAL试验中主要毒性结局的发生率为17.4%（149例患者中的26例），而对照组WBI加追加剂量照射队列中的发生率为72.7%（176例患者中的128例）（P <.001）。在纵向多变量分析中，OPAL试验治疗与患者报告的美容效果改善（P <.001）、功能状态改善（P =.004）、乳房疼痛改善（P =.004）和医生报告的美容效果改善（P <.001）相关。
与WBI加追加剂量照射相比，每日PBI治疗可显著降低早期毒性，并改善患者和医生报告的结局。每日13次或更少分割的外照射部分乳腺照射值得进一步进行前瞻性评估。
