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食管癌术前诱导放疗剂量应该多大?

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食管癌术前诱导放疗剂量应该多大?
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目前术前诱导放射治疗食管癌的剂量差异很大,CROSS 研究为41.1Gy,CALGB 9781研究剂量50.4Gy, 中国的研究NEOCRTEC5010,该项研究采用的也是40Gy的照射剂量。 还有好多研究的剂量在35-45Gy,所以术前诱导剂量差异较大,那么什么才是最佳的剂量,最近Ann Thorac Surg和 J Gastrointest Surg 各发表一篇关于食管癌的诱导放射治疗:剂量是否会影响预后结果的文章。

Ann Thorac Surg : Induction Radiation Therapy for Esophageal Cancer: Does Dose Affect Outcomes?

BACKGROUND:
Wide variation is seen in the dosage of preoperative induction radiation therapy for esophageal cancer. We investigated associations between outcomes after esophagectomy and dosage of induction radiation therapy.
METHODS:
Patients undergoing induction radiation therapy (30 to 70 Gy), followed by esophagectomy, were identified from the National Cancer Database and classified as low (<40 Gy), standard (40 to 50.4 Gy), and high dose (>50.4 Gy). Perioperative outcomes and overall survival were compared. Subgroup analysis compared two common dosages: 45 Gy and 50.4 Gy.
RESULTS:
From 2004 to 2014, 10,738 patients (84.7%) received standard-dose radiation, increasing from 69.7% in 2004 to 93.6% in 2014 (p < 0.001), 1,329 (10.5%) received low-dose radiation, and 608 (4.8%) received high-dose radiation. Higher rates of pathologic complete response (pCR; low: 11.7%, standard: 16.2%, high: 21.0%; p < 0.001) and downstaging (low: 52.0%, standard: 56.4%, high: 63.1%, p = 0.001) were observed as the dosage increased. On multivariable analysis, compared with standard-dose, high-dose radiation was associated with higher 30-day mortality (odds ratio [OR], 2.11; p < 0.001) without a higher likelihood of downstaging or pCR. Low-dose radiation was associated with lower likelihood of downstaging (OR, 0.85; p = 0.04) and pCR (OR, 0.67; p < 0.001) without lowering the risk of 30-day mortality. The dose of 50.4 Gy was associated with higher likelihood of pCR (OR, 1.12; p = 0.04), without affecting 30-day mortality, compared with 45 Gy.
CONCLUSIONS:
High-dose induction radiation (>50.4 Gy) is associated with increased perioperative death after esophagectomy, without a significant improvement in tumor response. Low-dose radiation (<30 Gy) is associated with worse tumor response without a lower risk of perioperative death. Within standard dosages, 50.4 Gy is associated with higher likelihood of pCR without adversely affecting perioperative mortality compared with 45 Gy.

方法:

数据来源国家数据库,选取接受诱导放射治疗(30至70Gy),然后进行食管切除术的患者,并将其分类:低剂量(<40Gy),标准剂量(40至50.4Gy)和高剂量(> 50.4Gy)。然后比较围手术期结果和总体生存率。并亚组分析比较了两种常用剂量:40-45 Gy和45.1-50.4 Gy。

结果:

从2004年到2014年,10738名患者(84.7%)接受标准剂量辐射,从2004年的69.7%增加到2014年的93.6%(p <0.001),1,329(10.5%)接受低剂量辐射,608(4.8%) )接受高剂量辐射。

随着照射剂量的增强,可见病理完全缓解率升高(pCR;低:11.7%,标准:16.2%,高:21.0%; p <0.001)和病理分期下调明显(低:52.0%,标准:56.4%,高:63.1%,p = 0.001)。

在多变量分析中,与标准剂量相比,高剂量放疗与较高的30天死亡率相关,却没有表现出更好的分期下调或pCR的可能性。低剂量辐射降低了分期下调和PCR的可能性,同时也不降低30天死亡率的风险。与45Gy相比,50.4Gy的剂量与较高的pCR可能性(OR,1.12; p = 0.04)相关,却不影响30天的死亡率。

结论:

高剂量诱导照射(> 50.4 Gy)与食管切除术后围手术期死亡增加有关,肿瘤放疗反应无明显改善。低剂量辐射(<30Gy)肿瘤放疗反应较差,但围手术期死亡的风险较低。在标准剂量范围内,与45Gy相比,50.4Gy与更高的pCR可能性相关,而不会对围手术期死亡率产生不利影响。

看似作者好像更新倾向50.4Gy的照射剂量。

J Gastrointest Surg :Influence of Neoadjuvant Radiation Dose on Patients Undergoing Esophagectomy and Survival in Locally Advanced Esophageal Cancer.

Abstract
BACKGROUND:
Neoadjuvant chemoradiotherapy followed by resection is standard of care for patients with locally advanced esophageal cancer, however, a significant portion of these patients do not undergo surgical intervention. This study evaluates radiation dose and other factors associated with undergoing esophageal resection and their impact on outcomes including survival.
METHODS:
Patients diagnosed with esophageal cancer between 2010 and 15 were queried from the National Cancer Database and stratified into low-dose radiation (41.4 Gy) (LDR) or high-dose radiation (50.0 or 50.4 Gy) (HDR) groups. Multivariable Logistic and Cox Regression analyses were performed to investigate the effect of multiple variables on the likelihood of undergoing esophagectomy and overall survival, respectively. Propensity score matching was performed to reduce bias between groups.
RESULTS:
A total of 3633 patients met study criteria with 3005 (82.7%) undergoing esophagectomy. A greater proportion received HDR (3163 (87.1%)) than LDR (470 (12.9%)). The use of LDR increased from 4.7% (n = 22) in 2010 to 20.7% (n = 154) in 2015. Factors associated with undergoing esophagectomy included LDR, adenocarcinoma histology, and younger age. Radiation dosage did not impact overall survival, but undergoing esophagectomy was associated with improved survival. After propensity matching, a greater portion of the LDR group underwent esophagectomy (87.0 vs 81.1%, p = 0.013). There was no difference in R0 3 resection (93.2 vs 92.4%, p = 0.678) or complete pathologic response (19.3 vs 21.5%, p = 0.442) between LDR and HDR groups.
CONCLUSION:
The use of LDR is increasing but still underutilized. LDR is associated with increased rates of esophagectomy without negatively impacting overall survival, R0 resection, or complete pathologic response.

方法

从国家癌症数据库查询2010年至2015年间被诊断患有食道癌的患者,并将其分为低剂量辐射(41.4Gy)(LDR)或高剂量辐射(50.0或50.4Gy)(HDR)组。进行多变量Logistic和Cox回归分析以分别研究多个变量对进行食管切除术和总体存活的可能性的影响。

结果

共有3633名患者符合研究标准,其中3005名(82.7%)接受了食管切除术。接收HDR的比例(3163(87.1%))高于LDR(470(12.9%))。LDR的使用从 2010年的4.7%(n = 22)增加到 2015 年的20.7%(n = 154)。食管切除术相关的因素包括LDR,腺癌和年龄。照射剂量不影响总体存活率,但行食管切除术可提高存活率。在倾向匹配后,大部分LDR组接受了食管切除术(87.0对81.1%,p  = 0.013)。R0切除率(93.2 vs 92.4%,p  = 0.678)或完全病理反应CPR(19.3 vs 21.5%,p = 0.442)在LDR和HDR组之间无明显差别。

结论

LDR的使用正在增加,但仍未得到充分利用。LDR与食管切除率增加有关,而不会对总体存活率,R0切除或完全病理反应产生负面影响。

这里作者更倾向于41.4Gy的低剂量组。

所以在具体照射剂量上目前尚无具体的定论,但从两篇文章看来,主要还是倾向于一个标准照射剂量:40-50.4Gy之间,具体实施可能存在差异。

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