Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects.
Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects.
复制标题
DOI：
10.1038/sj.bjc.6602301
复制
发表时间：
2005-02-14
影响因子：
8.8
通讯作者：
Horwich, A
中科院分区：
文献类型：
--
作者：
Dearnaley, DP;Hall, E;Lawrence, D;Huddart, RA;Eeles, R;Nutting, CM;Gadd, J;Warrington, A;Bidmead, M;Horwich, A
根治性放射治疗是治疗局限性前列腺癌的标准形式。适形治疗计划可以保护邻近的正常组织，减少与治疗相关的副作用，并可能允许安全的剂量递增。我们测试了增加放疗剂量对肿瘤控制的影响和副作用，并研究了适当的靶体积裕度。经过最初 3-6 个月的雄激素抑制期后，126 名男性被随机分配并采用 2 × 2 析因试验设计接受放射治疗。初始放疗肿瘤靶区包括前列腺和精囊基底 (SV) 或完整 SV，具体取决于 SV 受累风险。治疗随机分配为 64Gy 剂量，肿瘤体积周围有 1.0 或 1.5cm 边缘（1.0 和 1.5cm 边缘组），也可以单独对前列腺进行 10Gy 或不增加 10Gy 剂量，没有额外边缘（64 和 74Gy 组）。通过前列腺特异性抗原（PSA）测试和临床检查以及适当的额外测试来监测肿瘤控制。使用放射治疗和肿瘤组 (RTOG) 和 LENT SOM 系统测量治疗的急性和晚期副作用。结果显示，74Gy 组的 PSA 失败率高于 64Gy 组，但这并未达到传统的统计显着水平，74Gy 组的 5 年精算控制率为 71%（95% CI 58-81%），而 64Gy 组为 59%（95% CI 45-70%）。 74Gy 组有 23 例失败，64Gy 组有 33 例失败（风险比 0.64，95% CI 0.38-1.10，P=0.10）。 1.0厘米和1.5厘米边缘组之间的疾病控制没有差异（5年精算控制率67%，95% CI 53-77% vs 63%，95% CI 50-74%），每组有28个事件（风险比0.97，95% CI 0.50-1.86，P=0.94）。急性副作用一般较轻微，治疗 18 周后，126 名男性中只有 4 名和 5 名分别出现持续性 1 级肠道或膀胱副作用。接受 74 Gy 治疗的男性治疗后，急性膀胱副作用显着增加（P=0.006），而 1.5cm 切缘组的男性在治疗期间急性肠道副作用（P=0.05）和急性膀胱后遗症（P=0.002）均有所增加。虽然统计上显着，但这些差异持续时间较短，临床重要性值得怀疑。随机分组后的前 2 年，晚期肠道副作用 (RTOG⩾2) 在 74Gy 和 1.5cm 边缘组中更为常见（分别为 P=0.02 和 P=0.05）。使用 LENT SOM 评估也发现了类似的结果。使用 RTOG 评分系统，随机分组之间的晚期膀胱副作用没有显着差异。使用 LENT SOM 仪器，74Gy 组中接受治疗的男性在 6 个月和 12 个月时出现⩾3 级尿频的比例较高。与基线评分相比，所有组的膀胱症状在 6 个月或更长时间的随访后均得到改善。治疗后性功能恶化，报告有性功能障碍（1 级）的男性人数从基线时的 38% 增加到 6 个月和 1 年时的 66%，到第 5 年时增加到 81%。然而，随机组之间没有发现一致的差异。总之，使用适形放疗将剂量从 64 Gy 增加到 74 Gy 可能会改善长期 PSA 控制，但 1.5 cm 的治疗裕度是不必要的，并且会增加急性肠道和膀胱反应以及更多的晚期直肠副作用。这项随机试点研究的数据通知了医学研究委员会 RT 01 试验的数据监测委员会，两项研究将在随后的荟萃分析中合并。
Radical radiotherapy is a standard form of management of localised prostate cancer. Conformal treatment planning spares adjacent normal tissues reducing treatment-related side effects and may permit safe dose escalation. We have tested the effects on tumour control and side effects of escalating radiotherapy dose and investigated the appropriate target volume margin. After an initial 3–6 month period of androgen suppression, 126 men were randomised and treated with radiotherapy using a 2 by 2 factorial trial design. The initial radiotherapy tumour target volume included the prostate and base of seminal vesicles (SV) or complete SV depending on SV involvement risk. Treatments were randomised to deliver a dose of 64 Gy with either a 1.0 or 1.5 cm margin around the tumour volume (1.0 and 1.5 cm margin groups) and also to treat either with or without a 10 Gy boost to the prostate alone with no additional margin (64 and 74 Gy groups). Tumour control was monitored by prostate-specific antigen (PSA) testing and clinical examination with additional tests as appropriate. Acute and late side effects of treatment were measured using the Radiation Treatment and Oncology Groups (RTOG) and LENT SOM systems. The results showed that freedom from PSA failure was higher in the 74 Gy group compared to the 64 Gy group, but this did not reach conventional levels of statistical significance with 5-year actuarial control rates of 71% (95% CI 58–81%) in the 74 Gy group vs 59% (95% CI 45–70%) in the 64 Gy group. There were 23 failures in the 74Gy group and 33 in the 64 Gy group (Hazard ratio 0.64, 95% CI 0.38–1.10, P=0.10). No difference in disease control was seen between the 1.0 and 1.5 cm margin groups (5-year actuarial control rates 67%, 95% CI 53–77% vs 63%, 95% CI 50–74%) with 28 events in each group (Hazard ratio 0.97, 95% CI 0.50–1.86, P=0.94). Acute side effects were generally mild and 18 weeks after treatment, only four and five of the 126 men had persistent ⩾Grade 1 bowel or bladder side effects, respectively. Statistically significant increases in acute bladder side effects were seen after treatment in the men receiving 74 Gy (P=0.006), and increases in both acute bowel side effects during treatment (P=0.05) and acute bladder sequelae (P=0.002) were recorded for men in the 1.5 cm margin group. While statistically significant, these differences were of short duration and of doubtful clinical importance. Late bowel side effects (RTOG⩾2) were seen more commonly in the 74 Gy and 1.5 cm margin groups (P=0.02 and P=0.05, respectively) in the first 2 years after randomisation. Similar results were found using the LENT SOM assessments. No significant differences in late bladder side effects were seen between the randomised groups using the RTOG scoring system. Using the LENT SOM instrument, a higher proportion of men treated in the 74 Gy group had Grade ⩾3 urinary frequency at 6 and 12 months. Compared to baseline scores, bladder symptoms improved after 6 months or more follow-up in all groups. Sexual function deteriorated after treatment with the number of men reporting some sexual dysfunction (Grade⩾1) increasing from 38% at baseline to 66% at 6 months and 1 year and 81% by year 5. However, no consistent differences were seen between the randomised groups. In conclusion, dose escalation from 64 to 74 Gy using conformal radiotherapy may improve long-term PSA control, but a treatment margin of 1.5 cm is unnecessary and is associated with increased acute bowel and bladder reactions and more late rectal side effects. Data from this randomised pilot study informed the Data Monitoring Committee of the Medical Research Council RT 01 Trial and the two studies will be combined in subsequent meta-analysis.
登录
查看更多内容
DOI：
10.1016/s0360-3016(02)02940-1
发表时间：
2002-10-01
影响因子：
7
作者：
D'Amico, AV;Chen, MH;Richie, JP
通讯作者：
Richie, JP
影响因子：
6.6
作者：
Laverdière, J;Nabid, A;Harel, F
通讯作者：
Harel, F
DOI：
10.1016/s0360-3016(00)00441-7
发表时间：
2000-05-01
影响因子：
7
作者：
Fiveash, JB;Hanks, G;Sandler, HM
通讯作者：
Sandler, HM
影响因子：
5.7
作者：
Khoo, VS;Bedford, JL;Dearnaley, DP
通讯作者：
Dearnaley, DP
DOI：
10.1016/s0360-3016(96)00513-5
发表时间：
1997-01-15
影响因子：
7
作者：
Laverdiere, J;Gomez, JL;Labrie, F
通讯作者：
Labrie, F