Borger J H, Kemperman H, Smitt H S, Hart A, van Dongen J, Lebesque J, Bartelink H
Department of Radiotherapy, Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis, Amsterdam.
Int J Radiat Oncol Biol Phys. 1994 Dec 1;30(5):1073-81. doi: 10.1016/0360-3016(94)90312-3.
To analyze factors involved in the development of fibrosis in the boost area after breast conservation therapy (BCT) in patients treated with continuous low dose rate iridium implants following 50 Gy whole breast irradiation.
Fibrosis was estimated by palpation in 404 patients by four physicians. The median follow-up (FUP) duration was 70 months (range 30-133 months). Original implant data were used for reconstruction and dose-volume calculations. The total dose of the external whole breast irradiation and iridium implants was expressed in Normalized Total Dose (NTD): the total dose given in fractions of 2 Gy, which is biologically equivalent to the actual dose given according to the linear-quadratic model, using an alpha/beta value of 2 Gy, and 1.5 h for the recovery half-life of sublethal damage repair. To identify predictors of fibrosis we used a proportional odds model in a polychotomous logistic regression analysis.
Seven independent factors were identified that were related to the severity of fibrosis: age, duration of FUP, clinical T-size, photon beam energy, NTD level, implant volume, and adjuvant chemotherapy. From the proportional odds model, a volume exponent could be estimated (0.16 +/- 0.04) that enabled us to determine dose-effect relations for different volumes. A 10-fold higher risk of fibrosis was seen when the total dose was above 79 Gy as compared with doses lower than 70 Gy. A fourfold increase in risk of fibrosis was seen for each 100 cm3 increase in irradiated boost volume. The use of adjuvant chemotherapy resulted in a twofold increase in the risk of fibrosis (dose modifying factor approximately 1.08). The application of Co-60 beams had a similar effect. The relative odds for the other factors were smaller (1.4 for each 10 years of older age, and 1.2 for clinical T-size over 20 mm). The FUP-period had a nonlinear effect: relative odds 2.2 at 6 years, 3.6 at 7-8 years, and 2.8 at 9-11 years. The dose rate (mean 0.57, range 0.26-0.89 Gy/h) had no influence on the development of fibrosis and there was no correlation between dose rate and irradiated volume.
To optimize cosmetic results after BCT, both the total dose and the irradiated volume should be kept as low as possible. Minimum effective dose levels still have to be established. The boost volume can be minimized by more conformal brachytherapy techniques and optimal localization. It may be worthwhile to take adjuvant chemotherapy into account in decisions on boost dose levels.
分析在全乳照射50 Gy后接受连续低剂量率铱植入治疗的保乳治疗（BCT）患者中，瘤床区域纤维化发生的相关因素。
由四位医生通过触诊对404例患者的纤维化情况进行评估。中位随访时间为70个月（范围30 - 133个月）。利用原始植入数据进行重建和剂量 - 体积计算。全乳外照射和铱植入的总剂量以归一化总剂量（NTD）表示：以2 Gy分次给予的总剂量，根据线性 - 二次模型，使用α/β值2 Gy以及亚致死性损伤修复的恢复半衰期1.5小时，该剂量在生物学上等同于实际给予的剂量。为了确定纤维化的预测因素，我们在多分类逻辑回归分析中使用了比例优势模型。
确定了七个与纤维化严重程度相关的独立因素：年龄、随访时间、临床T分期、光子束能量、NTD水平、植入体积和辅助化疗。从比例优势模型中，可以估计出一个体积指数（0.16±0.04），这使我们能够确定不同体积的剂量 - 效应关系。与低于70 Gy的剂量相比，总剂量高于79 Gy时，纤维化风险高出10倍。照射瘤床体积每增加100 cm³，纤维化风险增加四倍。辅助化疗的使用使纤维化风险增加两倍（剂量修正因子约为1.08）。钴 - 60束的应用有类似效果。其他因素的相对优势较小（每增加10岁为1.4，临床T分期大于20 mm为1.2）。随访期有非线性效应：6年时相对优势为2.2，7 - 8年时为3.6，9 - 11年时为2.8。剂量率（平均0.57，范围0.26 - 0.89 Gy/h）对纤维化的发生没有影响，且剂量率与照射体积之间没有相关性。
为了优化保乳治疗后的美容效果，总剂量和照射体积都应尽可能保持低水平。仍需确定最小有效剂量水平。可以通过更适形的近距离放疗技术和最佳定位将瘤床体积最小化。在决定瘤床剂量水平时考虑辅助化疗可能是值得的。
