Liao Z, Strom E A, Buzdar A U, Singletary S E, Hunt K, Allen P K, McNeese M D
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Int J Radiat Oncol Biol Phys. 2000 Jul 15;47(5):1191-200. doi: 10.1016/s0360-3016(00)00561-7.
To evaluate the effect of radiation dose escalation on locoregional control, overall survival, and long-term complication in patients with inflammatory breast cancer.
From September 1977 to December 1993, 115 patients with nonmetastatic inflammatory breast cancer were treated with curative intent at The University of Texas M. D. Anderson Cancer Center. The usual sequence of multimodal treatment consisted of induction FAC or FACVP chemotherapy, mastectomy (if the tumor was operable), further chemotherapy, and radiation therapy to the chest wall and draining lymphatics. Sixty-one patients treated from September 1977 to September 1985 received a maximal radiation dose of 60 Gy to the chest wall and 45-50 Gy to the regional lymph nodes, 22 treated once a day at 2 Gy per fraction, and 35 were treated b.i.d. (32 after mastectomy and all chemotherapy was completed, and 2 immediately after mastectomy; one patient had distant metastases discovered during b.i.d. irradiation, and treatment was stopped). Four additional patients received preoperative radiation with standard fractionation. Based on the analysis of the failure patterns of the patients, the dose was increased for the b.i.d. patients in the new series, with 51 Gy delivered to the chest wall and regional nodes, followed by a 15-Gy boost to the chest wall with electrons. From January 1986 to December 1993, 39 patients were treated b.i.d. to this higher dose after mastectomy and all the chemotherapy was completed; and 8 additional patients received preoperative irradiation with b.i.d. fractionation to 51 Gy. During this period, another 7 patients were treated using standard daily doses of 2 Gy per fraction to a total of 60 Gy, either because they had a complete response or minimal residual disease at mastectomy or because their work schedule did not permit the b.i.d. regimen. Comparison was made between the groups for locoregional control, disease-free and overall survival, and complication rates.
The median follow-up time was 5.7 years (range, 1.8-17.6 years). For the entire patient group, the 5- and 10-year local control rates were 73.2% and 67.1%, respectively. The 5- and 10-year disease-free survival rates were 32.0% and 28.8%, respectively, and the overall survival rates for the entire group were 40.5% and 31.3%, respectively. To evaluate the effectiveness of dose escalation, a specific comparison of patients who received b.i.d. radiation after mastectomy and completion of adjuvant chemotherapy was performed. There were 32 patients treated b.i.d. to 60 Gy in the old series versus 39 patients treated b.i.d. to 66 Gy in the new series. There was an significant improvement in the rate of locoregional control for the b.i.d. patients for the old vs. new series, from 57.8% to 84.3% and from 57.8% to 77.0% (p = 0.028) at 5 and 10 years, respectively. Chemotherapy regimens did not change significantly during this time period.Long-term complications of radiation, such as arm edema more than 3 cm (7 patients), rib fracture (10 patients), severe chest wall fibrosis (4 patients), and symptomatic pneumonitis (5 patients), were comparable in the two groups, indicating that the dose escalation did not result in increased morbidity. Significant differences in the rates of locoregional control (p = 0.03) and overall survival (p = 0.03), and a trend of better disease-free survival (p = 0.06) were also observed that favored the recently treated patients receiving the higher doses of irradiation.
Twice-daily postmastectomy radiation to a total of 66 Gy for patients with inflammatory breast cancer resulted in improved locoregional control, disease free survival, and overall survival, and was well tolerated.
评估增加放疗剂量对炎性乳腺癌患者局部区域控制、总生存期及长期并发症的影响。
1977年9月至1993年12月,115例非转移性炎性乳腺癌患者在德克萨斯大学MD安德森癌症中心接受了根治性治疗。多模式治疗的通常顺序包括诱导性FAC或FACVP化疗、乳房切除术(如果肿瘤可手术)、进一步化疗以及胸壁和引流淋巴结放疗。1977年9月至1985年9月治疗的61例患者,胸壁最大放疗剂量为60 Gy,区域淋巴结为45 - 50 Gy,22例每天照射一次,每次2 Gy,35例每天照射两次(32例在乳房切除术后且所有化疗完成后进行,2例在乳房切除术后立即进行;1例患者在每天两次照射期间发现远处转移,治疗停止)。另外4例患者接受了标准分割的术前放疗。基于对患者失败模式的分析,新系列中每天两次照射的患者剂量增加,胸壁和区域淋巴结给予51 Gy,随后用电子线对胸壁追加15 Gy照射。1986年1月至1993年12月,39例患者在乳房切除术后且所有化疗完成后接受每天两次的更高剂量照射;另外8例患者接受每天两次分割至51 Gy的术前照射。在此期间,另有7例患者因乳房切除术后完全缓解或残留病灶极少,或因工作安排不允许每天两次照射方案,而采用每天2 Gy的标准日剂量照射至总量60 Gy。对两组患者的局部区域控制、无病生存期和总生存期以及并发症发生率进行了比较。
中位随访时间为5.7年(范围1.8 - 17.6年)。对于整个患者组,5年和10年局部控制率分别为73.2%和67.1%。5年和10年无病生存率分别为32.0%和28.8%,整个组的总生存率分别为40.5%和31.3%。为评估增加剂量的有效性,对乳房切除术后且辅助化疗完成后接受每天两次放疗的患者进行了具体比较。旧系列中有32例患者每天两次照射至60 Gy,新系列中有39例患者每天两次照射至66 Gy。旧系列与新系列中每天两次照射的患者在5年和10年时局部区域控制率有显著提高,分别从57.8%提高到84.3%和从57.8%提高到77.0%(p = 0.028)。在此期间化疗方案无显著变化。放疗的长期并发症,如手臂水肿超过3 cm(7例)、肋骨骨折(10例)、严重胸壁纤维化(4例)和有症状的肺炎(5例),在两组中相当,表明增加剂量并未导致发病率增加。在局部区域控制率(p = 0.03)和总生存期(p = 0.03)方面也观察到显著差异,并且在无病生存期方面有更好的趋势(p = 0.06),有利于近期接受更高剂量照射的患者。
炎性乳腺癌患者乳房切除术后每天两次放疗至总量66 Gy可改善局部区域控制、无病生存期和总生存期,且耐受性良好。