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Long-term outcomes of definitive radiotherapy-based comprehensive treatment for inoperable stage I-III non-metastatic pancreatic cancer
Cao Biyang1,2, Liu Xiaoliang2, Zhang Letian1,2, Wu Chenchen1,2, Yang Wei2, Wang Qianqian2, Tong Fang2, Wang Jing2
1Chinese PLA Medical School, Beijing 100853, China; 2Department of Radiation Oncology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
AbstractObjective To analyze long-term outcomes of inoperable non-metastatic pancreatic cancer patients treated with definitive radiotherapy-based comprehensive treatment. Methods Clinical data of 168 patients with medically unfit, refusal to surgery or inoperable non-metastatic pancreatic cancer treated with radiotherapy-based comprehensive treatment in PLA General Hospital between January 2016 and December 2020 were retrospectively analyzed. Survival outcomes,prognostic factors and patterns of treatment failure were analyzed in the radiotherapy (n=95) and combined chemoradiotherapy (n=73) groups. The survival analysis was conducted by Kaplan-Meier method. The survival curve was compared by log-rank test. Independent prognostic factors were identified by Cox proportional harzard model. Results With a median follow-up of 20.2 months in the entire group, the median overall survival (OS) and median progression-free survival (PFS) were 18.0 and 12.3 months. The corresponding median OS and median PFS after receiving radiotherapy were 14.3 and 7.7 months. The 1-, 2-and 3-year OS rates were 72.1%, 36.6% and 21.5%, and the 1- and 2-year local control rates were 82.6% and 64.3%, respectively. The median OS for stage Ⅰ, stage Ⅱ and stage III were 27.1, 18.0 and 17.0 months, respectively. There was no significant difference in the median OS of patients with localized disease (stage Ⅰ-Ⅱ) between the radiotherapy and combined chemoradiotherapy groups (21.1 vs. 20.4 months, P=0.470). In patients with locally advanced disease (stage Ⅲ), combined chemoradiotherapy group showed better median OS compared with radiotherapy group (19.2 vs. 13.8 months, P=0.004). Clinical stage, CA19-9 before radiotherapy, comprehensive treatment and biological effective dose (BED10) were identified as the independent prognostic factors for OS (P=0.032, 0.011, 0.003 and 0.014). The cumulative 1- and 2-year actuarial rates of treatment failure, local-regional recurrence and distant metastasis were 48% and 74.4%, 15.0% and 27.4%, 23.6% and 33.1%, respectively. Liver metastasis (16.1%, 27/168) and local recurrence (11.9%, 20/168) were the primary patterns of treatment failure. Conclusions Definitive radiotherapy-based comprehensive treatment effectively prolongs long-term survival in patients with inoperable non-metastatic pancreatic cancer. Definitive radiotherapy can be an alternative treatment option with curative intent for patients with localized pancreatic cancer who are medically unfit or refuse to undergo surgery. The combination of radiotherapy and chemotherapy remains an effective treatment choice for locally advanced unresectable pancreatic cancer.
Fund:National Key Research and Development Program (2017YFC0112104)
Corresponding Authors:
Wang Jing, Email: wangjingmd@hotmail.com
Cite this article:
Cao Biyang,Liu Xiaoliang,Zhang Letian et al. Long-term outcomes of definitive radiotherapy-based comprehensive treatment for inoperable stage I-III non-metastatic pancreatic cancer[J]. Chinese Journal of Radiation Oncology, 2023, 32(5): 407-414.
Cao Biyang,Liu Xiaoliang,Zhang Letian et al. Long-term outcomes of definitive radiotherapy-based comprehensive treatment for inoperable stage I-III non-metastatic pancreatic cancer[J]. Chinese Journal of Radiation Oncology, 2023, 32(5): 407-414.
[1] Chen X, Yi B, Liu Z, et al.Global, regional and national burden of pancreatic cancer, 1990 to 2017: results from the global burden of disease study 2017[J]. Pancreatology, 2020,20(3):462-469. DOI: 10.1016/j.pan.2020.02.011. [2] Mizrahi JD, Surana R, Valle JW, et al.Pancreatic cancer[J]. Lancet, 2020,395(10242):2008-2020. DOI: 10.1016/S0140-6736(20)30974-0. [3] National Cancer Institude.Cancer stat facts: pancreatic cancer[EB/OL].[2022-02-26].https://seer.cancer.gov/statfacts/html/pancreas.html. [4] Grossberg AJ, Chu LC, Deig CR, et al.Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma[J]. CA Cancer J Clin, 2020,70(5):375-403. DOI: 10.3322/caac.21626. [5] de Geus S, Eskander MF, Kasumova GG, et al. Stereotactic body radiotherapy for unresected pancreatic cancer: a nationwide review[J]. Cancer, 2017,123(21):4158-4167. DOI: 10.1002/cncr.30856. [6] Chin V, Nagrial A, Sjoquist K, et al. Chemotherapy and radiotherapy for advanced pancreatic cancer[J]. Cochrane Database Syst Rev, 2018,3(3):CD011044. DOI: 10.1002/14651858.CD011044.pub2. [7] Schizas D, Charalampakis N, Kole C, et al.Immunotherapy for pancreatic cancer: a 2020 update[J]. Cancer Treat Rev, 2020,86:102016. DOI: 10.1016/j.ctrv.2020.102016. [8] National Comprehensive Cancer Network. Pancreatic adenocarcinoma (version 2. 2021)[EB/OL].[2022-02- 26]. http://www.nccn.org/professionals/physician_gls/default.aspx. [9] Timmerman R.A story of hypofractionation and the table on the wall[J]. Int J Radiat Oncol Biol Phys, 2022,112(1):4-21. DOI: 10.1016/j.ijrobp.2021.09.027. [10] Cox JD, Stetz J, Pajak TF.Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC)[J]. Int J Radiat Oncol Biol Phys, 1995,31(5):1341-1346. DOI: 10.1016/0360-3016(95)00060-C. [11] Wang J, Xia T, Wang Y, et al. Long-term results of gamma ray-based stereotactic body radiation therapy in treatment of medically unfit or inoperable nonmetastatic pancreatic adenocarcinoma[J]. Int J Radiat Oncol Biol Phys, 2012, 84 (3): S815-S816. DOI: 10.1016/j.ijrobp.2012.07.2182. [12] 常冬姝, 夏廷毅, 李平, 等. 全身γ刀治疗局限期胰腺癌临床结果分析[J].中华放射肿瘤学杂志,2009,18(6):470-473. DOI: 10.3760/cma.j.issn.1004-4221.2009.06.470. Chang DS, Xia TY, Li P, et al.Clinical outcome of whole body γ-knife for limited pancreatic carcinoma[J]. Chin J Radiat Oncol, 2009,18(6):470-473. DOI: 10.3760/cma.j.issn.1004-4221.2009.06.470. [13] 李光, 于洋洋, 韩冲, 等. 81例胰腺癌后程加量三维适形放疗的疗效分析[J].中国医科大学学报,2012,41(12):1134-1137,1143. DOI: 10.3969/j.issn.0258-4646.2012.12.022. Li G, Yu YY, Han C, et al.Efficacy analysis of three-dimensional conformal radiotherapy with increasing dose in late course in 81 cases of pancreatic cancer patients[J]. Journal of China Medical University, 2012,41(12):1134-1137,1143. DOI: 10.3969/j.issn.0258-4646.2012.12.022. [14] Kamarajah SK, Burns WR, Frankel TL, et al.Validation of the American Joint Commission on Cancer (AJCC) 8th edition staging system for patients with pancreatic adenocarcinoma: a surveillance, epidemiology and end results (SEER) analysis[J]. Ann Surg Oncol, 2017,24(7):2023-2030. DOI: 10.1245/s10434-017-5810-x. [15] Park W, Chawla A, O'Reilly EM. Pancreatic cancer: a review[J]. JAMA, 2021,326(9):851-862. DOI: 10.1001/jama.2021.13027. [16] Gemenetzis G, Groot VP, Blair AB, et al.Survival in locally advanced pancreatic cancer after neoadjuvant therapy and surgical resection[J]. Ann Surg, 2019,270(2):340-347. DOI: 10.1097/SLA.0000000000002753. [17] 中华医学会外科学分会胰腺外科学组. 中国胰腺癌诊治指南(2021)[J].中华外科杂志,2021,59(7):561-577. DOI: 10.3760/cma.j.cn112139-20210416-00171. Pancreatic Surgery Group of Chinese Medical Association. Guidelines for the diagnosis and treatment of pancreatic cancer in China(2021)[J].Chinese Journal of Surgery,2021,59(7):561-577. DOI: 10.3760/cma.j.cn112139-20210416-00171. [18] Palta M, Godfrey D, Goodman KA, et al.Radiation therapy for pancreatic cancer: executive summary of an ASTRO clinical practice guideline[J]. Pract Radiat Oncol, 2019,9(5):322-332. DOI: 10.1016/j.prro.2019.06.016. [19] Huguet F, André T, Hammel P, et al.Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies[J]. J Clin Oncol, 2007,25(3):326-331. DOI: 10.1200/JCO.2006.07.5663. [20] Sr LPJ, Feng Y, Cardenes H, et al.Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial[J]. J Clin Oncol, 2011,29(31):4105-4112. DOI: 10.1200/JCO.2011.34.8904. [21] Hammel P, Huguet F, van Laethem JL, et al. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 randomized clinical trial[J]. JAMA, 2016,315(17):1844-1853. DOI: 10.1001/jama.2016.4324. [22] Chauffert B, Mornex F, Bonnetain F, et al.Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study[J]. Ann Oncol, 2008,19(9):1592-1599. DOI: 10.1093/annonc/mdn281. [23] Suker M, Beumer BR, Sadot E, et al.FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis[J]. Lancet Oncol, 2016,17(6):801-810. DOI: 10.1016/S1470-2045(16)00172-8. [24] Stein SM, James ES, Deng Y, et al.Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer[J]. Br J Cancer, 2016,114(7):737-743. DOI: 10.1038/bjc.2016.45. [25] Kunzmann V, Siveke JT, Algül H, et al.Nab-paclitaxel plus gemcitabine versus nab-paclitaxel plus gemcitabine followed by FOLFIRINOX induction chemotherapy in locally advanced pancreatic cancer (NEOLAP-AIO-PAK- 0113): a multicentre, randomised, phase 2 trial[J]. Lancet Gastroenterol Hepatol, 2021,6(2):128-138. DOI: 10.1016/S2468-1253(20)30330-7. [26] Hussung S, Akhoundova D, Hipp J, et al.Longitudinal analysis of cell-free mutated KRAS and CA 19-9 predicts survival following curative resection of pancreatic cancer[J]. BMC Cancer, 2021,21(1):49. DOI: 10.1186/s12885-020-07736-x. [27] Kondo N, Murakami Y, Uemura K, et al.Prognostic impact of perioperative serum CA 19-9 levels in patients with resectable pancreatic cancer[J]. Ann Surg Oncol, 2010,17(9):2321-2329. DOI: 10.1245/s10434-010-1033-0. [28] Krishnan S, Chadha AS, 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.
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