Arcangeli G, Giovinazzo G, Saracino B, D'Angelo L, Giannarelli D, Arcangeli G, Micheli A
Radiation Therapy Center, S. Maria Goretti Hospital, Latina, Italy.
Int J Radiat Oncol Biol Phys. 1998 Dec 1;42(5):1119-26. doi: 10.1016/s0360-3016(98)00264-8.
In order to better define variables and factors that may influence the pain response to radiation, and to look for a radiation regimen that can assure the highest percentage and the longest duration of pain relief, we performed a prospective, although not randomized, study on patients with bone metastases from various primary sites.
From December 1988 to March 1994, 205 patients with a total of 255 solitary or multiple bone metastases from several primary tumors were treated in our radiotherapy center with palliative intent. Irradiation fields were treated with three main fractionation schedules: (1) Conventional fractionation: 40-46 Gy/20-23 fractions in 5-5.5 weeks; (2) Short course: 30-36 Gy/10-12 fractions in 2-2.3 weeks; (3) Fast course: 8-28 Gy/1-4 consecutive fractions. Pain intensity was self-assessed by patients using a visual analogic scale graduated from 0 (no pain) to 10 (the strongest pain one can experience). Analgesic requirement was assessed by using a five-point scale, scoring both analgesic strength and frequency (0 = no drug or occasional nonopioids; 1 = Nonopioids once daily; 2 = Nonopioids more than once daily; 3 = Mild opioids (oral codeine, pentazocine, etc.), once daily; 4 = Mild opioids more than once daily; 5 = Strong opioids (morphine, meperidine, etc.). Complete pain relief meant the achievement of a score < or = 2 in the pain scale or 0 in the analgesic requirement scale. Partial pain relief indicated a score of 3 to 4 or of 1 to 2 on the former and latter scale, respectively.
Total pain relief (complete + partial) was observed in 195 (76%) sites, in 158 of which (62%) a complete response was obtained. Metastases from NSC lung tumors appeared to be the least responsive among all primary tumors, with 46% complete pain relief in comparison to 65% and 83% complete relief in breast (p = 0.04) and in prostate metastases (p = 0.002), respectively. A significant difference in pain relief was detected among the several ranges of total dose delivered to the painful metastases, with 81%, 65%, and 46% complete relief rates in the 40-46 Gy, 30-36 Gy (p = 0.03), and 8-28 Gy (p = 0.0001) dose ranges respectively. A straight correlation between total dose and complete pain relief was confirmed by the curve calculated by the logistic model which shows that doses of 30 Gy or more are necessary to achieve complete pain relief in 70% or more of bone metastases. This correlation holds also for the duration of pain control, as shown by the actuarial analysis of time to pain progression. Multivariate analyses, with complete pain relief and time to pain progression as endpoints show a highly significant effect of radiation dose (p = 0.0007) and performance status (p = 0.003), with lower rates of complete pain relief and shorter time to pain progression observed after smaller radiation total doses or higher Eastern Cooperative Oncology Group (ECOG) scores.
Although single-dose or short course irradiation is an attractive treatment in reducing the number of multiple visits to radiotherapy departments for patients with painful bone metastases, it is nevertheless clear that aggressive protracted treatments seem to offer significant advantages especially for patients in whom the expected life span is not short.
为了更好地界定可能影响放射治疗疼痛反应的变量和因素，并寻找一种能确保最高疼痛缓解率和最长缓解持续时间的放疗方案，我们对来自不同原发部位的骨转移患者进行了一项前瞻性研究（尽管未随机分组）。
1988年12月至1994年3月，我们放疗中心对205例患者共255处单发或多发骨转移灶进行了姑息性治疗，这些骨转移灶来自多种原发肿瘤。照射野采用三种主要的分割方案进行治疗：（1）常规分割：40 - 46 Gy/20 - 23次分割，在5 - 5.5周内完成；（2）短程分割：30 - 36 Gy/10 - 12次分割，在2 - 2.3周内完成；（3）快速分割：8 - 28 Gy/1 - 4次连续分割。患者使用从0（无疼痛）到10（所能体验到的最强烈疼痛）的视觉模拟评分法进行自我疼痛强度评估。使用五点量表评估镇痛药物需求，对镇痛药物的强度和使用频率进行评分（0 = 未用药或偶尔使用非阿片类药物；1 = 每日使用一次非阿片类药物；2 = 每日使用非阿片类药物超过一次；3 = 轻度阿片类药物（口服可待因、喷他佐辛等），每日一次；4 = 轻度阿片类药物每日使用超过一次；5 = 强效阿片类药物（吗啡、哌替啶等））。完全疼痛缓解意味着疼痛量表评分≤2或镇痛药物需求量表评分为0。部分疼痛缓解分别指在前一量表上评分为3至4分，或在后一量表上评分为1至2分。
在195处（76%）观察到完全疼痛缓解（完全缓解 + 部分缓解），其中158处（62%）获得完全缓解。在所有原发肿瘤中，非小细胞肺癌转移灶的反应似乎最差，完全疼痛缓解率为46%，而乳腺癌转移灶和前列腺癌转移灶的完全缓解率分别为65%和83%（p = 0.04）（p = 0.002）。在给予疼痛转移灶的不同总剂量范围内，疼痛缓解存在显著差异，40 - 46 Gy、30 - 36 Gy（p = 0.03）和8 - 28 Gy（p = 0.0001）剂量范围内的完全缓解率分别为81%、65%和46%。逻辑模型计算的曲线证实了总剂量与完全疼痛缓解之间的直接相关性，该曲线表明，要使70%或更多的骨转移灶实现完全疼痛缓解，需要30 Gy或更高的剂量。正如疼痛进展时间的精算分析所示，这种相关性在疼痛控制持续时间方面也成立。以完全疼痛缓解和疼痛进展时间为终点的多变量分析显示，放射剂量（p = 0.0007）和体能状态（p = 0.003）具有高度显著影响，放射总剂量较小或东部肿瘤协作组（ECOG）评分较高时，完全疼痛缓解率较低，疼痛进展时间较短。
尽管单剂量或短程照射对于减少疼痛性骨转移患者到放疗科就诊的次数是一种有吸引力的治疗方法，但很明显，积极的延长疗程治疗似乎具有显著优势，特别是对于预期寿命不短的患者。
