原发肿瘤体积对鼻咽癌调强放疗预后的影响
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摘要
研究目的:探讨调强放射治疗条件下鼻咽癌原发肿瘤体积对患者预后的影响。
研究方法:我院自2004年1月至2006年12月共有330例UICC I-IVB期鼻咽癌初治患者接受调强放射治疗,入组本研究。所有患者治疗前均行CT增强扫描,扫描图像资料输人三维治疗计划系统进行肿瘤轮廓勾画,勾画完成后系统自动进行三维重建和肿瘤体积计算。我们在研究中用受试者工作特征曲线( receive operating characteristic curve, ROC曲线)确定原发肿瘤体积的临床应用截点,用Kaplan-Meier生存分析和COX比例风险回归模型分析原发肿瘤体积与患者预后的关系。
研究结果:330例鼻咽癌患者所测平均原发肿瘤体积是34.2ml(0.4-153.7)。对于T1、T2、T3和T4患者,平均原发肿瘤体积分别是10.4ml(0.4-40.6)、21.9ml(3.6-75.3)、34.0ml(4.6-102.1)和68.2ml(18.9-153.7)。在2002UICC鼻咽癌T分期框架内,所有入组患者被分为4组,分组的截点是由ROC曲线确定的,分别是10ml、25ml、50ml。建立在原发肿瘤体积分组基础上,三年总生存率对于四组患者分别是88.6%, 90.0%, 91.2%和74.2% (p=0.005)。前三组累积生存率曲线非常贴近,但与第四组曲线分离明显。对于第四组患者即原发肿瘤体积超过50ml的患者,生存率较前三组明显下降。多因素分析中亦证实原发肿瘤体积同N分期一样,是影响患者生存的一个独立预后因素。
结论:鼻咽癌原发肿瘤体积是影响患者生存的一个极其重要的预后因素。临床使用UICC分期评估患者预后和治疗方案时,应该充分考虑到患者原发肿瘤体积对预后的影响。我们基于该研究基础上建议考虑将原发肿瘤体积作为一个新的分期指标,补充和完善现行的鼻咽癌分期。
Background: The prognostic factors are quite complex for patients with nasopharyngeal carcinoma (NPC), and more important factors include tumour stage and radical treatment. According to the current staging system, NPC is T-staged by local anatomic location, and no quantitative criteria of tumor volume are taken into account. The theory is the foundation upon which the longer the tumor grows, the wider the range the local anatomic location involved, and the more poor the treatment effect. Intensity-modulated radiation therapy (IMRT) , which is considered as a landmark development in radiation therapy, has gradually become standard technique for NPC. The purpose of this study was to explore the effect of primary tumor volume on treatment outcomes in patients with NPC who were treated with IMRT.
Objective: The purpose of this study was to conduct an institutional review analyzing the correlation between primary tumor volume (PTV) and prognosis of NPC treated with IMRT.
Methods: 330 patients from January 2004 to December 2006 with UICC I-IVB NPC treated by IMRT were included. PTV was measured from pretreatment computerized tomography scans. Image data were input into 3D treatment-planning system. which can automatically reconstruct 3D image and calculate primary tumor volume. Receiver operating characteristics (ROC) curve was used to determine the cut-off point of PTV. Kaplan - Meier survival analysis and COX proportion risk regression model were used to analysis the correlation between PTV and prognosis of NPC treated with IMRT.
Results: The mean PTV for all NPC patients was 34.2(ml)±27.1 (SD) with the range of 0.4–153.7ml. The mean PTV for T1, T2, T3 and T4 were 10.4m(l0.4-40.6)、21.9ml(3.6-75.3)、34.0m(l4.6-102.1)and 68.2m(l18.9-153.7). The ROC curve was used to determine the cut-off point of PTV. Within the framework of UICC T stage,we divided all the patients into four groups (V1 <10ml, V2 10-25ml, V3 25-50ml, and V4 >50ml). In accordance with the volume-based groups mentioned above, the 3-year OS for V1, V2, V3 and V4 stage were 88.6%,90.0%,91.2% and 74.2%, respectively (p=0.005). The cumulative survival curves for V1, V2 and V3 are very close, but clearly separated from V4. Survival analysis demonstrated a significant difference in overall survival with larger PTV (>50ml). Multivariate analysis revealed that primary tumor volume was a adverse prognostic factors for overall survival.
Conclusions: Our study demonstrated primary tumor volume had significantly impacted on the prognosis of patients with NPC. Within the framework of UICC TNM staging system,we should consider the effect of primary tumor volume on prognosis. We proposed that primary tumor volume should be considered as an additional stage indicator in the new revision of clinical stage of NPC.
研究方法:我院自2004年1月至2006年12月共有330例UICC I-IVB期鼻咽癌初治患者接受调强放射治疗,入组本研究。所有患者治疗前均行CT增强扫描,扫描图像资料输人三维治疗计划系统进行肿瘤轮廓勾画,勾画完成后系统自动进行三维重建和肿瘤体积计算。我们在研究中用受试者工作特征曲线( receive operating characteristic curve, ROC曲线)确定原发肿瘤体积的临床应用截点,用Kaplan-Meier生存分析和COX比例风险回归模型分析原发肿瘤体积与患者预后的关系。
研究结果:330例鼻咽癌患者所测平均原发肿瘤体积是34.2ml(0.4-153.7)。对于T1、T2、T3和T4患者,平均原发肿瘤体积分别是10.4ml(0.4-40.6)、21.9ml(3.6-75.3)、34.0ml(4.6-102.1)和68.2ml(18.9-153.7)。在2002UICC鼻咽癌T分期框架内,所有入组患者被分为4组,分组的截点是由ROC曲线确定的,分别是10ml、25ml、50ml。建立在原发肿瘤体积分组基础上,三年总生存率对于四组患者分别是88.6%, 90.0%, 91.2%和74.2% (p=0.005)。前三组累积生存率曲线非常贴近,但与第四组曲线分离明显。对于第四组患者即原发肿瘤体积超过50ml的患者,生存率较前三组明显下降。多因素分析中亦证实原发肿瘤体积同N分期一样,是影响患者生存的一个独立预后因素。
结论:鼻咽癌原发肿瘤体积是影响患者生存的一个极其重要的预后因素。临床使用UICC分期评估患者预后和治疗方案时,应该充分考虑到患者原发肿瘤体积对预后的影响。我们基于该研究基础上建议考虑将原发肿瘤体积作为一个新的分期指标,补充和完善现行的鼻咽癌分期。
Background: The prognostic factors are quite complex for patients with nasopharyngeal carcinoma (NPC), and more important factors include tumour stage and radical treatment. According to the current staging system, NPC is T-staged by local anatomic location, and no quantitative criteria of tumor volume are taken into account. The theory is the foundation upon which the longer the tumor grows, the wider the range the local anatomic location involved, and the more poor the treatment effect. Intensity-modulated radiation therapy (IMRT) , which is considered as a landmark development in radiation therapy, has gradually become standard technique for NPC. The purpose of this study was to explore the effect of primary tumor volume on treatment outcomes in patients with NPC who were treated with IMRT.
Objective: The purpose of this study was to conduct an institutional review analyzing the correlation between primary tumor volume (PTV) and prognosis of NPC treated with IMRT.
Methods: 330 patients from January 2004 to December 2006 with UICC I-IVB NPC treated by IMRT were included. PTV was measured from pretreatment computerized tomography scans. Image data were input into 3D treatment-planning system. which can automatically reconstruct 3D image and calculate primary tumor volume. Receiver operating characteristics (ROC) curve was used to determine the cut-off point of PTV. Kaplan - Meier survival analysis and COX proportion risk regression model were used to analysis the correlation between PTV and prognosis of NPC treated with IMRT.
Results: The mean PTV for all NPC patients was 34.2(ml)±27.1 (SD) with the range of 0.4–153.7ml. The mean PTV for T1, T2, T3 and T4 were 10.4m(l0.4-40.6)、21.9ml(3.6-75.3)、34.0m(l4.6-102.1)and 68.2m(l18.9-153.7). The ROC curve was used to determine the cut-off point of PTV. Within the framework of UICC T stage,we divided all the patients into four groups (V1 <10ml, V2 10-25ml, V3 25-50ml, and V4 >50ml). In accordance with the volume-based groups mentioned above, the 3-year OS for V1, V2, V3 and V4 stage were 88.6%,90.0%,91.2% and 74.2%, respectively (p=0.005). The cumulative survival curves for V1, V2 and V3 are very close, but clearly separated from V4. Survival analysis demonstrated a significant difference in overall survival with larger PTV (>50ml). Multivariate analysis revealed that primary tumor volume was a adverse prognostic factors for overall survival.
Conclusions: Our study demonstrated primary tumor volume had significantly impacted on the prognosis of patients with NPC. Within the framework of UICC TNM staging system,we should consider the effect of primary tumor volume on prognosis. We proposed that primary tumor volume should be considered as an additional stage indicator in the new revision of clinical stage of NPC.
引文
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[2] Cheng SH, Tsai SY, Yen KC, et al.Improvement of local control of T3 and T4 nasopharyngeal carcinoma by hyperfractionat- ed radiotherapy and concomitant chemotherapy. Int J Radiat Oncol Biol Phys. 2002;53(2):344-52.
[3] Wolden SL, Zelefsky MJ, Kraus DH, et al. Accelerated concomitant boost radiotherapy and chemotherapy for advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2006;64(1):57-62.
[4] Lu JJ, Kong L, Shakespeare TP, et al.Prospective phase II trial of concomitant boost radiotherapy for stage II nasopharyngeal carcinoma. Oral Oncol. 2008;44(7):703-9.
[5] Lee AW, Lau WH, Tung SY, et al.Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group. J Clin Oncol. 2005;23(28): 6966-75.
[6] Chen Y, Liu MZ, Liang SB, et al. Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china. Int J Radiat Oncol Biol Phys. 2008;71(5):1356-64.
[7] Kam MK,Chan RM, Suen J,et a1. Intensity-modulated radiotherapy in nasopharyngeal carcinoma: dosimetric advantage over conventional plans and feasibility of dose escalation.Int J Radiat Oncol Biol Phys. 2003;56:145-157.
[8] Tee PM, Ma BB, Chan AT. Radiotherapy for nasopharyngeal carcinoma-transltion from two-dimensional to three—dimensional methnds.Radiother Oncol.2004;73:163-172.
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