局部晚期胰腺癌75 Gy同步加量放射治疗的剂量可行性研究

doi:10.19401/j.cnki.1007-3639.2023.01.006

摘要/Abstract

摘要：

背景与目的：近年来，胰腺癌的发病率逐年上升，调强放射治疗（intensity-modulated radiotherapy，IMRT）已被广泛应用于胰腺癌的治疗，但多数胰腺癌IMRT的剂量学研究的处方剂量都小于60 Gy。本研究旨在探究局部晚期胰腺癌（locally advanced pancreatic cancer，LAPC）患者75 Gy同步加量放射治疗的剂量可行性并比较共面IMRT（coplanar IMRT，CO-IMRT）与非共面IMRT（non-coplanar IMRT，NC-IMRT）技术的剂量学差异。方法：纳入复旦大学附属肿瘤医院2018年1月—2021年12月收治的符合入组标准的10例接受同步加量放射治疗的LAPC患者，处方剂量为50 Gy的计划靶区（planning target volume，PTV），记为PTV_{50 Gy}，处方剂量为75 Gy同步加量的PTV，记为PTV_{75 Gy}，靶区照射分次均为25次。为每例患者分别设计CO-IMRT和NC-IMRT计划。同1例患者两种计划的射野数、处方剂量和危及器官（organs at risk，OAR）的优化条件完全相同。统计CO-IMRT和NC-IMRT计划的靶区剂量分布、适形性指数（conformity index，CI）、均匀性指数（homogeneity index，HI）、OAR剂量学结果、出束时间和机器跳数（monitor units，MU）。评估靶区是否满足临床要求以及OAR剂量限值是否符合临床正常组织效应定量分析（quantitative analysis of normal tissue effects in the clinic，QUANTEC）要求，并比较CO-IMRT计划与NC-IMRT计划之间的剂量学差异。结果：CO-IMRT和NC-IMRT均可达到靶区剂量覆盖要求并满足QUANTEC的剂量限值要求。两种PTV的CI、HI、出束时间和MU之间的差异无统计学意义（P>0.05）。在左侧肾D_mean[（10.15±1.53）Gy vs（9.29±1.78）Gy，P<0.05]、左侧肾V₁₂[（32.74±7.45）% vs（26.03±8.97）%，P<0.05]、右侧肾D_mean[（7.37±2.41）Gy vs（6.62±2.37）Gy，P<0.05]、右侧肾V₁₂[（22.27±10.30）% vs（14.94±8.62）%，P<0.05]、肝V₃₀[（6.37±4.05）% vs（5.47±3.70）%，P<0.05]、小肠V₃₀[（9.96±6.66）% vs（8.73±6.19）%，P<0.05]、小肠V₄₅[（1.15±0.71）% vs（0.96±0.61）%，P<0.05]、胃V₄₅[（5.37±3.96）% vs（4.52±3.32）%，P<0.05]、大肠V₃₀[（13.18±4.95）% vs（9.19±4.94）%，P<0.05]指标上，NC-IMRT显著优于CO-IMRT，差异有统计学意义（P<0.05）。在脊髓D_max、肝D_mean、双侧肾V₂₀、双侧肾V₂₈、小肠D_max、胃D_max和十二指肠V_55（mL）指标上，CO-IMRT与NC-IMRT之间差异无统计学意义（P>0.05）。结论：基于75 Gy同步加量放射治疗治疗LAPC时，CO-IMRT和NC-IMRT均能达到靶区剂量覆盖要求并满足OAR剂量限值。在不影响靶区剂量覆盖质量的前提下，NC-IMRT在双肾、肝和胃肠道的剂量分布上更有优势，能够更好地保护OAR，降低放射治疗对胃肠道、肝和肾的毒性。

关键词: 局部晚期胰腺癌, 调强放射治疗, 剂量学

Abstract:

Background and purpose: The incidence of pancreatic cancer has increased annually. Intensity-modulated radiotherapy (IMRT) has been widely used in the treatment of pancreatic cancer, however most dosimetric studies for pancreatic cancer have prescribed doses less than 60 Gy. The purpose of this study was to investigate the feasibility and dosimetric differences between coplanar IMRT (CO-IMRT) and non-coplanar IMRT (NC-IMRT) when using 75 Gy simultaneous integrated boost for patients with locally advanced pancreatic cancer (LAPC). Methods: Ten patients with LAPC treated with simultaneous integrated boost at Fudan University Shanghai Cancer Center from January 2018 to December 2021 were included. The prescribed dose for the planning target volume (PTV)_{50 Gy} was 50 Gy in 25 fractions, and 75 Gy in 25 fractions for the simultaneous integrated boost PTV_{75 Gy}. CO-IMRT and NC-IMRT plans were designed for each patient separately, with identical number of fields, prescription doses and OAR constrains for the same patient. The PTV dose distribution, conformability index (CI), homogeneity index (HI), indices to organs at risk (OAR) for multiple end points, beam-on time and monitor units (MU) were analyzed. We evaluated whether the PTV met clinical requirements and quantitative analysis of normal tissue effects in the clinic (QUANTEC) limits, and compared dosimetric differences between the two plans. Results: Both CO-IMRT and NC-IMRT could achieve the required dose coverage of PTV and meet the QUANTEC dose limits for OAR. The differences in CI, HI, beam-on time and MU between the two plans were not statistically significant (P>0.05). NC-IMRT was significantly decreased left kidney D_mean[(10.15±1.53) Gy vs (9.29±1.78) Gy, P<0.05], left kidney V₁₂[(32.74±7.45)% vs (26.03±8.97)%, P<0.05], right kidney D_mean[(7.37±2.41) Gy vs (6.62±2.37)Gy, P<0.05], right kidney V₁₂[(22.27±10.30)% vs (14.94±8.62)%, P<0.05], liver V₃₀[(6.37±4.05)% vs (5.47±3.70)%, P<0.05], small intestine V₃₀[(9.96±6.66)% vs (8.73±6.19)%, P<0.05], small intestine V₄₅[(1.15±0.71)% vs (0.96±0.61)%, P<0.05], stomach V₄₅[(5.37±3.96)% vs (4.52±3.32)%, P<0.05] and large bowel V₃₀[(13.18±4.95)% vs (9.19±4.94)%, P<0.05]. There was no significant difference between CO-IMRT and NC-IMRT in spinal cord D_max, liver D_mean, bilateral renal V₂₀, bilateral renal V₂₈, small intestinal D_max, gastric D_max and duodenal V_55(mL) (P >0.05). Conclusion: In the treatment of LAPC using 75 Gy simultaneous integrated boost, both CO-IMRT and NC-IMRT can achieve excellent PTV coverage and meet the OAR constraints in all patients. Without affecting the quality of PTV coverage, NC-IMRT has more advantages in the dose distribution of OAR, which can better protect the OAR and reduce the toxicity to the gastrointestinal tract, liver and kidneys.

Key words: Locally advanced pancreatic cancer, Intensity-modulated radiotherapy, Dosimetry

中图分类号:

R735.9

庄晗, 凌池芳, 王佳舟, 韩序, 姜睿, 胡伟刚. 局部晚期胰腺癌75 Gy同步加量放射治疗的剂量可行性研究[J]. 中国癌症杂志, 2023, 33(1): 54-60.

ZHUANG Han, LING Chifang, WANG Jiazhou, HAN Xu, JIANG Rui, HU Weigang. Radiation therapy in locally advanced pancreatic cancer with 75 Gy simultaneous integrated boost: a dosimetric feasibility study[J]. China Oncology, 2023, 33(1): 54-60.

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参考文献 17

[1]	SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2018[J]. CA A Cancer J Clin, 2018, 68(1): 7-30. doi: 10.3322/caac.21442
[2]	RAMESH H. Management of pancreatic cancer: current status and future directions[J]. Indian J Surg, 2010, 72(4): 285-289. doi: 10.1007/s12262-010-0123-3 pmid: 21938189
[3]	REYNGOLD M, O’REILLY E M, VARGHESE A M, et al. Association of ablative radiation therapy with survival among patients with inoperable pancreatic cancer[J]. JAMA Oncol, 2021, 7(5): 735-738. doi: 10.1001/jamaoncol.2021.0057 pmid: 33704353
[4]	REYNGOLD M, PARIKH P, CRANE C H. Ablative radiation therapy for locally advanced pancreatic cancer: techniques and results[J]. Radiat Oncol, 2019, 14(1): 95. doi: 10.1186/s13014-019-1309-x pmid: 31171025
[5]	MARKS L B, YORKE E D, JACKSON A, et al. Use of normal tissue complication probability models in the clinic[J]. Int J Radiat Oncol Biol Phys, 2010, 76(3 Suppl): S10-S19. doi: 10.1016/j.ijrobp.2009.07.1754
[6]	HODAPP N. The ICRU Report 83: prescribing, recording and reporting photon-beam intensity-modulated radiation therapy (IMRT)[J]. Al, 2012, 188(1): 97-99.
[7]	IACOBUZIO-DONAHUE C A, FU B J, YACHIDA S, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer[J]. J Clin Oncol, 2009, 27(11): 1806-1813. doi: 10.1200/JCO.2008.17.7188
[8]	CRANE C H, VARADHACHARY G R, YORDY J S, et al. Phase Ⅱ trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4 (Dpc4) immunostaining with pattern of disease progression[J]. J Clin Oncol, 2011, 29(22): 3037-3043. doi: 10.1200/JCO.2010.33.8038
[9]	GUTT R, LIAUW S L, WEICHSELBAUM R R. The role of radiotherapy in locally advanced pancreatic carcinoma[J]. Nat Rev Gastroenterol Hepatol, 2010, 7(8): 437-447. doi: 10.1038/nrgastro.2010.98 pmid: 20628346
[10]	RUDRA S, JIANG N M, ROSENBERG S A, et al. Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer[J]. Cancer Med, 2019, 8(5): 2123-2132. doi: 10.1002/cam4.2100
[11]	KRISHNAN S, CHADHA A S, SUH Y, et al. Focal radiation therapy dose escalation improves overall survival in locally advanced pancreatic cancer patients receiving induction chemotherapy and consolidative chemoradiation[J]. Int J Radiat Oncol Biol Phys, 2016, 94(4): 755-765. doi: 10.1016/j.ijrobp.2015.12.003
[12]	SMYTH G, EVANS P M, BAMBER J C, et al. Recent developments in non-coplanar radiotherapy[J]. Br J Radiol, 2019, 92(1097): 20180908. doi: 10.1259/bjr.20180908
[13]	STEFANOWICZ S, STÜTZER K, ZSCHAECK S, et al. Comparison of different treatment planning approaches for intensity-modulated proton therapy with simultaneous integrated boost for pancreatic cancer[J]. Radiat Oncol, 2018, 13(1): 228. doi: 10.1186/s13014-018-1165-0 pmid: 30466468
[14]	DONG P, LEE P, RUAN D, et al. 4π non-coplanar liver SBRT: a novel delivery technique[J]. Int J Radiat Oncol Biol Phys, 2013, 85(5): 1360-1366. doi: 10.1016/j.ijrobp.2012.09.028
[15]	SOYFER V, CORN B W, MELAMUD A, et al. Three-dimensional non-coplanar conformal radiotherapy yields better results than traditional beam arrangements for adjuvant treatment of gastric cancer[J]. Int J Radiat Oncol Biol Phys, 2007, 69(2): 364-369. doi: 10.1016/j.ijrobp.2007.03.032
[16]	CHU J C, SOLIN L J, HWANG C C, et al. Three-dimensional dosimetric comparison of radiation therapy treatment planning of the pancreas[J]. Med Dosim, 1992, 17(4): 199-203. pmid: 1485907
[17]	DIAZ L, UREFIA A, CASTRO I, et al. 2062 POSTER comparative study between coplanar and non-coplanar techniques in radiotherapy of abdominal tumours[J]. Eur J Cancer, 2011, 47: S206-S207.

Structure	Requirement
PTV_{50 Gy}	The dose of 50 Gy includes at least 95% PTV_{50 Gy}
PTV_{75 Gy}	The dose of 75 Gy includes at least 95% PTV_{75 Gy}
Spinal cord	D_max<45 Gy
Liver	D_mean<18 Gy; V₃₀<50%
Kidney	D_mean<15 Gy; V₁₂<55%; V₂₀<32%; V₂₈<20%
Small intestine	D_max<54 Gy; V₃₀<25%; V₄₅<15%
Stomach	D_max<60 Gy; V₄₅<15%
Duodenum	V_55(mL)<1 cm³
Large bowel	V₃₀<50%

Item	CO-IMRT	NC-IMRT	P value
PTV_{50 Gy} CI	0.824±0.031	0.832±0.033	0.406
PTV_{75 Gy} CI	0.914±0.016	0.915±0.012	0.672
PTV_{75 Gy} HI	0.039±0.008	0.038±0.007	0.722

Structure	CO-IMRT	NC-IMRT	P value	Structure	CO-IMRT	NC-IMRT	P value
Spinal cord				V₂₀ /%	4.52±4.34	3.50±4.37	0.093
D_max /Gy	34.88±2.87	34.76±4.75	0.959	V₂₈ /%	1.05±1.53	1.42±2.28	0.463
Liver				Small intestine
D_mean /Gy	9.66±3.04	9.64±2.84	0.878	D_max /Gy	52.66±4.78	52.00±5.88	0.333
V₃₀ /%	6.37±4.05	5.47±3.70	0.013	V₃₀ /%	9.96±6.66	8.73±6.19	0.028
Left kidney				V₄₅ /%	1.15±0.71	0.96±0.61	0.024
D_mean /Gy	10.15±1.53	9.29±1.78	0.005	Stomach
V₁₂ /%	32.74±7.45	26.03±8.97	0.005	D_max /Gy	57.28±2.90	56.84.55±3.22	0.074
V₂₀ /%	11.14±6.65	10.19±5.12	0.575	V₄₅ /%	5.37±3.96	4.52±3.32	0.009
V₂₈ /%	4.18±3.15	4.91±3.21	0.059	Duodenum
Right kidney				V₅₅/mL	0.02±0.06	0.02±0.06	0.317
D_mean /Gy	7.37±2.41	6.62±2.37	0.005	Large bowel
V₁₂ /%	22.27±10.30	14.94±8.62	0.005	V₃₀ /%	13.18±4.95	9.19±4.94	0.005

Item	CO-IMRT	NC-IMRT	P value
Beam on time/min	2.55±0.45	2.56±0.38	0.799
MU	1529±270	1531±219	0.721