CARCINOMA OF THE UTERINE CERVIX .1. IMPACT OF PROLONGATION OF OVERALL TREATMENT TIME AND TIMING OF BRACHYTHERAPY ON OUTCOME OF RADIATION-THERAPY
CARCINOMA OF THE UTERINE CERVIX .1. IMPACT OF PROLONGATION OF OVERALL TREATMENT TIME AND TIMING OF BRACHYTHERAPY ON OUTCOME OF RADIATION-THERAPY
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DOI：
10.1016/0360-3016(95)00220-s
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发表时间：
1995-07-30
影响因子：
7
通讯作者：
LOCKETT, MA
中科院分区：
文献类型：
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作者：
PEREZ, CA;GRIGSBY, PW;LOCKETT, MA
目的：一些研究已经描述了当确定性照射过程中的总时间延长时，宫颈浸润癌的盆腔肿瘤控制和存活率降低。我们试图证实或否认这些观察结果，并评估近距离放射治疗的时间对结果的影响。我们还探讨了一个假设，即更广泛的肿瘤在技术上需要延长照射过程;因此，这些患者的肿瘤控制和生存率下降可能不一定是时间/剂量因素的结果。方法和材料：1224名患者的记录（IB至III期）接受确定性辐照治疗（结合外部射束和两次腔内插入，以向A点输送70至90戈伊的剂量）进行了审查。97%的患者获得随访（中位时间：12年;最短时间：3年;最长时间：28年）。结果和总体治疗时间和腔内插入时间之间的关系进行了分析，在每个阶段，并根据肿瘤的大小/extension.Results：有很强的相关性之间的总体治疗时间（OTT）和肿瘤分期（小于或等于7周：81%的阶段IB; 74%的阶段IIA; 52%的阶段IIB;和47%的阶段III）。25-30%的患者发生治疗中断导致治疗时间延长，最常见的原因是假期和周末以及治疗副作用。总体治疗时间对IB、IIA和IIB期盆腔肿瘤控制有重大影响;在IB期，10年精算盆腔失败率为7%，OTT ≤ 7周，7.1 - 9周为22%，>9周为36%（p ≤ 0.01）。IIA期的相应值分别为14%、27%和36%（p=0.08），IIB期的骨盆衰竭率分别为20%、28%和34%（p=0.09）。在III期，骨盆衰竭分别为30%、40%和50%（p = 0.08）。OTT与10年病因特异性生存期（CSS）之间也存在强相关性;在IB期，OTT ≤ 7周的发生率为86%，7.1 - 9周的发生率为78%，≥ 9周的发生率为55%（p=0.01）。III期疾病患者在9周或更短时间内接受治疗时的10年CSS为45%，在更长时间内接受治疗时为36%（p = 0.16）。在IB和IIA期患者的多变量分析中，OTT和临床分期是盆腔肿瘤控制、无病生存和CSS的最重要预后因素。肿瘤大小是CSS的预后因素。在IIB和III期，OTT、临床分期、单侧或双侧宫旁浸润和A点剂量是盆腔肿瘤控制、无病生存和CSS的重要预后因素。无论肿瘤大小如何，时间延长对盆腔肿瘤控制和CSS有显著影响，但小于或等于3 cm的IB期肿瘤除外。回归分析证实了之前的报告，即OTT延长导致所有患者的盆腔肿瘤控制率每天下降0.85%，IB和IIA期患者每天下降0.37%，IIB期患者每天下降0.68%，III期患者A点接受大于或等于85戈伊治疗时下降0.54%。在某些患者组中，在开始放射治疗后4.5周内进行所有腔内插入可降低骨盆衰竭率（IB期和IIA期肿瘤小于或等于4 cm时分别为8.8%和18%，IIB期分别为12.3%和35%）结论：延长IB、IIA、IIB和III期宫颈癌患者的治疗时间对盆腔肿瘤控制和CSS有显著影响。除了小于或等于3 cm的IB期肿瘤外，无论肿瘤大小如何，OTT的作用都存在。这可能与生物学因素有关，如治疗中断导致的细胞再增殖和增殖增加，以及初始克隆形成细胞负荷。宫颈浸润癌患者的放疗应在尽可能短的总时间内进行。
Purpose: Some studies have described decreased pelvic tumor control and survival rates in invasive carcinoma of uterine cervix when the overall time in a course of definitive irradiation is prolonged. We attempt to confirm or deny these observations and evaluate the impact of timing of brachytherapy on outcome. We also explore the hypothesis that more extensive tumors technically require prolongation of the course of irradiation; thus, decreased tumor control and survival in these patients may not necessarily be the result of time/dose factor.Methods and Materials: Records of 1224 patients (Stage IB to III) treated with definitive irradiation (combination of external beam and two intracavitary insertions to deliver doses of 70 to 90 Gy to point A) were reviewed. Follow-up was obtained in 97% of the patients (median, 12 years; minimum, 3 years; maximum, 28 years). The relationship between outcome and overall treatment time and time of intracavitary insertions was analyzed in each stage and according to tumor size/extent.Results: There was strong correlation between overall treatment time (OTT) and tumor stage (less than or equal to 7 weeks: 81% for Stage IB; 74% for Stage IIA; 52% for Stage IIB; and 47% for Stage III). Interruptions of therapy accounting for prolongation of treatment time occurred in 25-30% of patients, most frequently because of holidays and weekends and side effects of therapy. Overall treatment time had a major impact on pelvic tumor control in Stages IB, IIA, and IIB; in Stage IB 10-year actuarial pelvic failure rates were 7% with OTT less than or equal to 7 weeks, 22% with 7.1 to 9 weeks, and 36% with >9 weeks (p less than or equal to 0.01). For Stage IIA the corresponding values were 14%, 27%, and 36% (p=0.08), and in Stage IIB pelvic failure rates were 20%, 28%, and 34%, respectively (p=0.09). In Stage III, pelvic failure was 30%, 40%, and 50%, respectively (p = 0.08). There was also a strong correlation between OTT and 10-year cause-specific survival (CSS); in Stage IB rates were 86% with OTT of less than or equal to 7 weeks, 78% for 7.1 to 9 weeks, and 55% for greater than or equal to 9 weeks (p9 weeks (p=0.01). Patients with Stage III disease had 45% 10-year CSS when treatment was delivered in 9 weeks or less and 36% for longer overall times (p = 0.16). In multivariate analysis of patients with Stage IB and IIA, OTT and clinical stage were the most important prognostic factors for pelvic tumor control, disease-free survival, and CSS. Tumor size was a prognostic factor for CSS. In Stages IIB and III, OTT, clinical stage, unilateral or bilateral parametrial invasion, and dose to point A were significant prognostic factors for pelvic tumor control, disease-free survival, and CSS. Prolongation of time had a significant impact on pelvic tumor control and CSS regardless of tumor size, except in Stage IB tumors less than or equal to 3 cm. Regression analysis confirms previous reports that prolongation of OTT results in decreased pelvic tumor control rate of 0.85% per day for all patients, 0.37% per day in Stages IB and IIA, 0.68% per day in Stage IIB, and 0.54% for Stage III patients treated with greater than or equal to 85 Gy to point A. Performance of all intracavitary insertions within 4.5 weeks from initiation of irradiation yielded decreased pelvic failure rates in some groups of patients (8.8 vs. 18% in Stage IB and IIA tumors less than or equal to 4 cm and 12.3 vs. 35% in Stage IIB) (p less than or equal to 0.01).Conclusions: Prolongation of treatment time in patients with Stage IB, IIA, IIB, and III carcinoma of the uterine cervix has a significant impact on pelvic tumor control and CSS. The effect of OTT was present regardless of tumor size except in Stage IB tumors less than or equal to 3 cm. This may be related to biologic factors such as cell repopulation and increased proliferation resulting from treatment interruptions, in addition to initial clonogenic cell burden. Irradiation for patients with invasive carcinoma of the cervix should be delivered in the shortest possible overall time.