Mundt A J, Sibley G S, Williams S, Rubin S J, Heimann R, Halpern H, Weichselbaum R R
Department of Radiation and Cellular Oncology, Michael Reese/University of Chicago Center for Radiation Therapy, IL 60637.
Int J Radiat Oncol Biol Phys. 1994 Aug 30;30(1):151-60. doi: 10.1016/0360-3016(94)90530-4.
To determine the pattern of failure and outcome of patients achieving a complete response following high-dose chemotherapy and autologous bone marrow transplantation for metastatic breast cancer, and to evaluate the use of involved field radiation therapy in this setting.
Thirty-one patients with metastatic breast cancer treated on three successive high-dose chemotherapy and autologous bone marrow transplantation trials between January 1987 and March 1992 who achieved a complete response were evaluated. Twenty-three patients (74.2%) had initially Stage I-II disease. Initial therapy consisted of mastectomy in 19 (74.2%), adjuvant chemotherapy in 19 (61.3%), and adjuvant radiation therapy in 11 (35.5%). All patients underwent induction chemotherapy prior to high-dose intensification. High-dose chemotherapy consisted of cytoxan, thiotepa +/- carmustine. Fourteen patients received radiation therapy prior to (7) or following the high-dose chemotherapy (7) with either the intent to palliate a symptomatic disease site (4) or to attain/maintain a complete response (10). The four palliatively treated sites received 30 Gy in 3.0 Gy fractions, the sites treated definitively received a mean dose of 43.9 Gy (range, 18-64.8 Gy) in 1.5-2.0 Gy fractions. Seventy-two disease sites were present in the 31 patients. The most common sites involved were nodal (23), bone (14), and chest wall/breast (11). Nineteen sites were bulky (> 2 cm in size). Twenty-three sites were irradiated (19 definitively, 4 palliatively). Median follow-up was 18 months (range, 2-49 months).
Twenty (64.5%) of the 31 patients relapsed. Eleven of the 17 patients not receiving radiation failed. Seven (63.6%) failed first solely in sites of previous disease involvement and four (36.4%) failed in new sites. This failure pattern was reversed in the patients receiving radiation therapy. Nine of the 14 (64.3%) patients relapsed. Two (22.2%) failed solely in old sites and six (66.7%) solely in new sites. One patient (11.1%) failed simultaneously in both old and new sites. Patients receiving radiation therapy had a similar 2-year actuarial disease-free survival compared to those not treated with radiation (28.3% vs. 32.1%) (p = 0.14). However, patients with less than three sites of disease had a better disease-free survival at 2 years with the addition of radiation therapy (30.0% vs. 17.6%) (p = 0.03). Patients with locoregional disease only had a lower rate of local failure (one out of four vs. three out of five) and a longer mean time to any failure (4.0 months vs. 17.5 months) with the addition of radiation therapy. Of the 72 sites identified, 59 (81.9%) were amenable to radiation therapy either prior to or following the transplant. The use of radiation therapy resulted in a borderline significant improvement in 2-year actuarial control of all sites (82.4% vs. 64.3%) (p = 0.09) as well as of bulky sites (80.0% vs. 51.4%) (p = 0.08). Excluding the four sites treated with palliative intent only, the 2-year actuarial local control of the irradiated sites was 92.8%. None of the 14 treated patients experienced untoward sequelae.
The predominant site of initial failure in patients with metastatic breast cancer achieving a complete response following high-dose chemotherapy and autologous bone marrow transplantation is in sites of previous disease involvement. Radiation therapy given in conjunction with the high-dose chemotherapy is capable of improving the control of these sites, the majority of which are amenable to treatment with radiation therapy. Our data suggests that patients with less than three sites of disease, bulky disease, and locoregional disease only should be considered for radiation therapy in addition to high-dose chemotherapy.
确定转移性乳腺癌患者在接受大剂量化疗和自体骨髓移植后获得完全缓解的失败模式和预后，并评估在此情况下使用受累野放射治疗的效果。
对1987年1月至1992年3月期间在三项连续的大剂量化疗和自体骨髓移植试验中接受治疗且获得完全缓解的31例转移性乳腺癌患者进行评估。23例（74.2%）患者最初为I-II期疾病。初始治疗包括19例（74.2%）接受乳房切除术，19例（61.3%）接受辅助化疗，11例（35.5%）接受辅助放射治疗。所有患者在大剂量强化治疗前均接受诱导化疗。大剂量化疗包括环磷酰胺、噻替哌+/-卡莫司汀。14例患者在大剂量化疗前（7例）或后（7例）接受放射治疗，目的是缓解有症状的疾病部位（4例）或达到/维持完全缓解（10例）。4个接受姑息性治疗的部位以3.0 Gy的分次剂量给予30 Gy，明确治疗的部位以1.5 - 2.0 Gy的分次剂量给予平均43.9 Gy（范围18 - 64.8 Gy）。31例患者共有72个疾病部位。最常受累的部位是淋巴结（23个）、骨（14个）和胸壁/乳房（11个）。19个部位体积较大（>2 cm）。23个部位接受了放射治疗（19个为明确治疗，4个为姑息性治疗）。中位随访时间为18个月（范围2 - 49个月）。
31例患者中有20例（64.5%）复发。17例未接受放射治疗的患者中有11例失败。17例患者中有7例（63.6%）仅在先前疾病受累部位首次失败，4例（36.4%）在新部位失败。接受放射治疗的患者的这种失败模式则相反。14例患者中有9例（64.3%）复发。2例（22.2%）仅在旧部位失败，6例（66.7%）仅在新部位失败。1例患者（11.1%）在新旧部位同时失败。接受放射治疗的患者与未接受放射治疗的患者相比，2年无病生存率相似（28.3%对32.1%）（p = 0.14）。然而，疾病部位少于三个的患者在接受放射治疗后2年的无病生存率更高（30.0%对17.6%）（p = 0.03）。仅患有局部区域疾病的患者在接受放射治疗后局部失败率较低（四分之一对五分之三），至任何失败的平均时间更长（4.0个月对17.5个月）。在确定的72个部位中，59个（81.9%）在移植前或后适合接受放射治疗。放射治疗的使用使所有部位的2年精算控制率有临界显著改善（82.4%对64.3%）（p = 0.09），体积较大部位的控制率也有改善（80.0%对51.4%）（p = 0.08）。排除仅接受姑息性治疗的4个部位，接受放射治疗部位的2年精算局部控制率为92.8%。14例接受治疗的患者均未出现不良后遗症。
转移性乳腺癌患者在接受大剂量化疗和自体骨髓移植后获得完全缓解，其初始失败的主要部位是先前疾病受累部位。与大剂量化疗联合使用的放射治疗能够改善对这些部位的控制，其中大多数部位适合接受放射治疗。我们的数据表明，除大剂量化疗外，疾病部位少于三个、有体积较大疾病以及仅患有局部区域疾病的患者应考虑接受放射治疗。
