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Study of volume change and radioherapy timing in patients with stage Ⅳ non-small cell lung cancer by targeted therapy
Zhang Xia1,3, Zhang Yi2, Ouyang Weiwei2, Ma Zhu2, Li Qingsong2, Hu Yinxiang2, Geng Yichao2, Chen Xiaxia2, Li Xiaoyang2, Su Shengfa2, Lu Bing2
1 Department of Oncology, Guizhou Medical University, Guiyang 550025, China; 2 Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China; 3 Guihang Guiyang Hospital, Guiyang 550006, China
AbstractObjective To investigate the primary tumor volume change and timing of radiotherapy for patients with stage Ⅳ non-small cell lung cancer with EGFR mutation during molecular targeted therapy. Methods Simulated CT scanning measurement and analysis were performed to observe the volume changes of primary tumors before and after treatment with a time interval of 10 days in this prospective study. Positioning and volume measurement were terminated when the volume change was 5% or less between two time points before and after treatment or 90 days after treatment. Primary tumor radiation therapy was then performed, acute radiation-induced injury was recorded, and the implementation and simulation of related parameters of radiotherapy plans were compared. Results Twenty-nine of 30 cases were included in the analysis (1 case dropped off). After EGFR-TKIs treatment, the volume of all primary tumors was decreased, but the shrinking rate was inconsistent with the speed. Until the last simulated CT scanning, the maximum and minimum shrinking rates were 90% and 28%, respectively. There was no case of termination within 30 days of treatment, and the average tumor volume was significantly decreased within 40 days and the average tumor volume significantly differed every 10 days (P<0.001). After 40 days, the volume shrinking rate of primary tumors ≤5% gradually appeared, and one patient presented with a volume shrinking rate of >5% on 90 days. During this time, the average volume shrinking rate slowed down and became stable, ranging from 49.15% to 54.77%. Moreover, the average volume continued to gradually shrink after slight increase at 70 days. There was no significant difference in the average volume every 10 days (P>0.05). After the termination of simulated CT scanning, the dose of primary tumor was (69±7) Gy for patients receiving radiotherapy. Two patients had grade 2 acute radiation-induced pneumonitis and 3 patients had grade 3 acute radiation-induced pneumonitis. In addition, 1 patient had grade 2 radiation-induced esophagitis. According to the technology and dose parameters of radiotherapy plan, simulated radiotherapy plans before and 40 days after EGFR-TKIs treatment were designed. The timing of implementation plan was significantly better than that before EGFR-TKIs treatment (all P<0.05), whereas it was similar to that at 40 days after EGFR-TKI treatment (P>0.05). Conclusions The primary tumor shrinking rate is gradually slowed down over time after EGFR-TKIs treatment in patients with stage Ⅳ non-small cell lung cancer. The average tumor volume is significantly decreased within 40 days and then the shrinking rate becomes slow. The tumor shrinking rate of each case is inconsistent. Radiotherapy at 40 days after treatment is probably the optimal timing to obtain high dose and control radiation-induced injury.
Fund:Guizhou Science and Technology Plan Support Project [Qian Sci Co-support (2019) 2795]
Corresponding Authors:
Lu Bing, Email:lbgymaaaa@163.com
Cite this article:
Zhang Xia,Zhang Yi,Ouyang Weiwei et al. Study of volume change and radioherapy timing in patients with stage Ⅳ non-small cell lung cancer by targeted therapy[J]. Chinese Journal of Radiation Oncology, 2020, 29(8): 633-638.
Zhang Xia,Zhang Yi,Ouyang Weiwei et al. Study of volume change and radioherapy timing in patients with stage Ⅳ non-small cell lung cancer by targeted therapy[J]. Chinese Journal of Radiation Oncology, 2020, 29(8): 633-638.
[1] National Comprehensive Cancer Network. NCCN clinical practice guidelines in Oncology-Non-small cell lung cancer[DB/OL][2020-05-04].https://www.scienceopen.com/document?vid=a2e2292d-dacb-43c1-944f-d962cf61e7bb.
[2] Okamoto I, Mitsudomi T, Nakagawa K, et al. The emerging role of epidermal growth factor receptor (EGFR) inhibitors in first-line treatment for patients with advanced non-small cell lung cancer positive for EGFR mutations[J]. Ther Adv Med Oncol, 2010,2:301-307. DOI:10.1177/1758834010370698.
[3] Shaw AT, Yeap BY, Solomon BJ, et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement:a retrospective analysis[J]. Lancet Oncol, 2011, 12(11):1004-1012. DOI:10.1016/S1470-2045(11)70232-7.
[4] Mok TS, Wu Y, Ahn M, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer[J]. N Engl J Med, 2017, 376(7):629-640. DOI:10.1056/NEJMoa1612674.
[5] Hida T, Nokihara H, Kondo M, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX):an open-label, randomised phase 3 trial[J]. Lancet (ISO), 2017, 390(10089):29-39. DOI:10.1016/S0140-6736(17)30565-2.
[6] Shaw AT, Ou SI, Bang Y, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer[J]. N Engl J Med, 2014, 371(21):1963-1971. DOI:10.1056/NEJMoa1406766.
[7] Su SF, Hu YX, Ouyang WW, et al. Overall survival and toxicities regarding thoracic three-dimensional radiotherapy with concurrent chemotherapy for stage Ⅳ non-small cell lung cancer:results of a prospective single-center study[J]. BMC Cancer, 2013, 13:474. DOI:10.1186/1471-2407-13-474.
[8] Gray JE, Villegas A, Daniel D, et al. Three-year overall survival with durvalumab after chemoradiotherapy in stage Ⅲ NSCLC-Update from PACIFIC[J]. J Thorac Oncol, 2020, 15(2):288-293. DOI:10.1016/j.jtho.2019.10.002.
[9] Wang C, Lu X, Lyu Z, et al. Comparison of up-front radiotherapy and TKI with TKI alone for NSCLC with brain metastases and EGFR mutation:a meta-analysis[J]. Lung Cancer, 2018, 122(1):94-99. DOI:10.1016/j.1ungcan.2018.05.014.
[10] Lopez-Guerra JL, Gomez D, Zhuang Y, et al. Prognostic impact of radiation therapy to the primary tumor in patients with non-small cell lung cancer and oligometastasis at diagnosis[J]. Int J Radiat Oncol Biol Phys, 2012, 84(1):e61-e67. DOI:10.1016/j.ijrobp.2012.02.054.
[11] Ma JT, Zheng JH, Han CB, et al. Meta-analysis comparing higher and lower dose radiotherapy for palliation in locally advanced lung cancer[J]. Cancer Sci, 2014, 105(8):1015-1022. DOI:10.1111/cas.12466.
[12] Su S, Li T, Lu B, et al. Three-dimensional radiation therapy to the primary tumor with concurrent chemotherapy in patients with stage Ⅳ non-small cell lung cancer:results of a multicenter phase 2 study from PPRA-RTOG, China[J]. Int J Radiat Oncol Biol Phys, 2015, 93(4):769-777. DOI:10.1016/j.ijrobp.2015.08.012.
[13] Ouyang W, Su S, Hu Y, et al. Radiation dose and survival of patients with stage Ⅳ non-small cell lung cancer undergoing concurrent chemotherapy and thoracic three-dimensional radiotherapy:reanalysis of the findings of a single-center prospective study[J]. BMC Cancer, 2014, 14:491. DOI:10.1186/1471-2407-14-491.
[14] Gomez DR, Blumenschein GR, Lee JJ, et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy:a multicentre, randomised, controlled, phase 2 study[J]. Lancet Oncol, 2016, 17(12):1672-1682. DOI:10.1016/S1470-2045(16)30532-0.
[15] Uhlig J, Case MD, Blasberg JD, et al. Comparison of survival rates after a combination of local treatment and systemic therapy vs. systemic therapy alone for treatment of stage Ⅳ non-small cell lung cancer[J]. JAMA Network Open, 2019, 2(8):e199702. DOI:10.1001/jamanetworkopen.2019.9702.
[16] Koshy M, Malik R, Mahmood U, et al. Comparative effectiveness of aggressive thoracic radiation therapy and concurrent chemoradiation therapy in metastatic lung cancer[J]. Pract Radiat Oncol, 2015, 5(6):374-382. DOI:10.1016/j.prro.2015.07.009.
[17] Mok TS, Cheng Y, Zhou X, et al. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and egfr-activating mutations[J]. J Clin Oncol, 2018, 36(22):2244-2250. DOI:10.1200/JCO.2018.78.7994.
[18] Xia B, Wang J, Liu Q, et al. Quantitative analysis of tumor shrinkage due to chemotherapy and its implication for radiation treatment planning in limited-stage small-cell lung cancer[J]. Radiat Oncol, 2013, 8(1):216. DOI:10.1186/1748-717X-8-216.
[19] Gomez DR, Tang C, Zhang J, et al. Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer:long-term results of a multi-institutional, phase Ⅱ, randomized study[J]. J Clin Oncol, 2019, 37(18):1558-1565. DOI:10.1016/S1470-2045(16)30532-0.
[20] Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma[J]. N Engl J Med, 2009, 361(10):947-957. DOI:10.1200/JCO.2018.78.7994.
[21] Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC):a multicentre, open-label, randomised phase 3 trial[J]. Lancet Oncol, 2012, 13(3):239-246. DOI:10.1016/S1470-2045(11)70393-X.
[22] Oya Y, Yoshida T, Kuroda H, et al. Association between EGFR T790M status and progression patterns during initial EGFR-TKI treatment in patients harboring EGFR mutation[J]. Clin Lung Cancer, 2017, 18(6):698-705. DOI:10.1016/j.cllc.2017.05.004.
[23] Park DI, Kim SY, Kim JO, et al. The prognostic value of the tumor shrinkage rate for progression-free survival in patients with non-small cell lung cancer receiving gefitinib[J]. Tuberc Respir Dis (Seoul), 2015, 78(4):315-320. DOI:10.4046/trd.2015.78.4.315.
[24] 胡银祥,卢冰,周华宁,等. 非小细胞肺癌三维适形后程加速超分割放疗中肺剂量体积变化规律及临床意义探讨[J]. 中华放射肿瘤学杂志,2009,18(1):57-60.
Hu YX, Lu B, Zhou HN, et al. Changes of lung dose volume and its clinical significance in three-dimensional conformal late course accelerated hyperfractionation radiotherapy for non-small cell lung cancer[J]. Chin J Radiat Oncol,2009,18(1):57-60.
[25] Palma DA, Senan S, Tsujino K, et al. Predicting radiation pneumonitis after chemoradiation therapy for lung cancer:an international individual patient data meta-analysis[J]. Int J Radiat Oncol Biol Phys, 2013, 85(2):444-450. DOI:10.1016/j.ijrobp.2012.04.043.
[26] Marks LB, Yorke ED, Jackson A, et al. Use of normal tissue complication probability models in the clinic[J]. Int J Radiat Oncol Biol Phys, 2010, 76(3):S10-S19. DOI:10.1016/j.ijrobp.2009.07.1754.
[27] Liang J, Bi N, Wu S, et al. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage Ⅲ non-small cell lung cancer:a multicenter randomized phase Ⅲ trial[J]. Ann Oncol, 2017, 28(4):777-783. DOI:10.1093/annonc/mdx009.