1Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China; 2Department of Anesthesia, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China
AbstractObjective To evaluate the effect of different doses of thoracic radiotherapy (TRT) upon the clinical prognosis of patients with extensive-stage (stage Ⅳ) small cell lung cancer (ES-SCLC) and establish a Nomogram prediction model. Methods Clinical data of 144 patients pathologically diagnosed with ES-SCLC undergoing TRT in Tianjin Medical University Cancer Hospital from month,2010 to month,2016 were retrospectively analyzed. Clinical characteristics,treatment data and responses were evaluated. A Nomogram was established by using Cox’s proportional hazard regression model to predict the overall survival (OS).The prediction capability and accuracy were assessed by the concordance index (C-index) and a calibration curve between the model and verification groups. Results The median follow-up time was 31.9 months. The 2-year OS rate was 20.3%.The Nomogram model demonstrated that TRT dose,liver metastases,oligometastases/polymetastases,number of chemotherapy cycle and response to chemotherapy were significantly correlated with clinical prognosis. The calibration curve revealed that the predicted and actual OS were highly consistent. The C-index was calculated as 0.701.In the subgroup analyses,patients with high-dose TRT obtained significantly better OS than their counterparts with low-dose TRT. Conclusion The Nomogram prediction model based on different TRT doses can accurately predict the OS rate of ES-SCLC patients,which is an individualized model for predicting the survival probability.
Xu LiMing,Yuan Yajing,Luo Jing et al. Prognostic factors in patients with stage Ⅳ small cell lung cancer:A nomogram prediction model based on different doses of thoracic radiotherapy[J]. Chinese Journal of Radiation Oncology, 2019, 28(4): 268-273.
Xu LiMing,Yuan Yajing,Luo Jing et al. Prognostic factors in patients with stage Ⅳ small cell lung cancer:A nomogram prediction model based on different doses of thoracic radiotherapy[J]. Chinese Journal of Radiation Oncology, 2019, 28(4): 268-273.
[1] Chen W,Zheng R,Baade PD,et al. Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.DOI:10.3322/caac.21338. [2] Sheikh S,Shah A,Arshed A,et al. Histological pattern of primary malignant lung tumours diagnosed in a tertiary care hospital:10 year study[J].Asian Pac J Cancer Prev,2010,11(5):1341-1346. [3] Chen Y,Chen L,Zhong D.Comparing the adverse effects of platinum in combination with etoposide or irinotecan in previously untreated small-cell lung cancer patients with extensive disease:a network meta-analyses[J].Thorac Cancer,2017,8(3):170-180.DOI:10.1111/1759-7714.12420. [4] Siegel RL,Miller KD,Jemal A.Cancer statistics,2016[J].CA Cancer J Clin,2016,66(1):7-30.DOI:10.3322/caac.21332. [5] Zelen M.Keynote address on biostatistics and data retrieval[J].Cancer Chemother Rep,1973,4(2):31-42. [6] Woods NT,Monteiro AN,Thompson ZJ,et al. Interleukin polymorphisms associated with overall survival,disease-free survival,and recurrence in non-small cell lung cancer patients[J].Mol Carcinog,2015,54 Suppl 1:E172-184.DOI:10.1002/mc.22275. [7] Takahashi T,Yamanaka T,Seto T,et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer:a multicentre,randomised,open-label,phase 3 trial[J].Lancet Oncol,2017,18(5):663-671.DOI:10.1016/S1470-2045(17)30230-9. [8] Jeremic B,Shibamoto Y,Nikolic N,et al. Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer:a randomized study[J].J Clin Oncol,1999,17(7):2092-2099.DOI:10.1200/JCO.1999.17.7.2092. [9] Ou SH,Ziogas A,Zell JA.Prognostic factors for survival in extensive stage small cell lung cancer (ED-SCLC):the importance of smoking history,socioeconomic and marital statuses,and ethnicity[J].J Thorac Oncol,2009,4(1):37-43.DOI:10.1097/JTO.0b013e31819140fb. [10] Zhu H,Zhou Z,Wang Y,et al. Thoracic radiation therapy improves the overall survival of patients with extensive-stage small cell lung cancer with distant metastasis[J].Cancer,2011,117(23):5423-5431.DOI:10.1002/cncr.26206. [11] Zhang X,Yu J,Zhu H,et al. Consolidative thoracic radiotherapy for extensive stage small cell lung cancer[J].Oncotarget,2017,8(13):22251-22261.DOI:10.18632/ oncotarget.14759. [12] Mahmoud O,Kwon D,Greenfield B,et al. Intrathoracic extensive-stage small cell lung cancer:assessment of the benefit of thoracic and brain radiotherapy using the SEER database[J].Int J Clin Oncol,2016,21(6):1062-1070.DOI:10.1007/s10147-016-1011-z. [13] Palma DA,Warner A,Louie AV,et al. Thoracic radiotherapy for extensive stage small-cell lung cancer:a Meta-analysis[J].Clin Lung Cancer,2016,17(4):239-244.DOI:10.1016/j.cllc.2015.09.007. [14] Slotman BJ,van Tinteren H,Praag JO,et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer:a phase 3 randomised controlled trial[J].Lancet,2015,385(9962):36-42.DOI:10.1016/S0140-6736(14)61085-0. [15] Slotman BJ,van Tinteren H.Which patients with extensive stage small-cell lung cancer should and should not receive thoracic radiotherapy?[J].Transl Lung Cancer Res,2015,4(3):292-294.DOI:10.3978/j.issn.2218-6751.2015.04.07. [16] Liang W,Zhang L,Jiang G,et al. Development and validation of a nomogram for predicting survival in patients with resected non-small-cell lung cancer[J].J Clin Oncol,2015;33(8):86186-9.DOI:10.1200/JCO.2014.56.6661. [17] Xie D,Marks R,Zhang M,et al. Nomograms Predict Overall Survival for Patients with Small-Cell Lung Cancer Incorporating Pretreatment Peripheral Blood Markers[J].J Thorac Oncol,2015,10(8):1213-1220.DOI:10.1097/JTO.0000000000000585. [18] Zeng Q,Xue N,Dai D,et al. A Nomogram based on inflammatory factors C-ractive protein and fibrinogen to predict the prognostic value in patients with resected non-small cell lung cancer[J].J Cancer,2017,8(5):744-753.DOI:10.7150/jca.17423. [19] Yang Y,Zhang YJ,Zhu Y,et al. Prognostic nomogram for overall survival in previously untreated patients with extranodal NK/T-cell lymphoma,nasal-type:a multicenter study[J].Leukemia,2015,29(7):1571-1577.DOI:10.1038/leu.2015.44. [20] Yao JC,Hassan M,Phan A,et al. One hundred years after"carcinoid":epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States[J].J Clin Oncol,2008,26(18):3063-3072.DOI:10.1200/JCO.2007.15.4377. [21] Fowler JF.The linear-quadratic formula and progress in fractionated radiotherapy[J].Br J Radiol,1989,62(740):679-94.DOI:10.1259/0007-1285-62-740-679. [22] Hellman S,Weichselbaum RR.Oligometastases[J].J Clin Oncol,1995,13(1):8-10.DOI:10.1200/JCO.1995.13.1.8. [23] Eisenhauer EA,Therasse P,Bogaerts J,et al. New response evaluation criteria in solid tumours:revised RECIST guideline (version 1.1)[J].Eur J Cancer,2009,45(2):228-247.DOI:10.1016/j.ejca.2008.10.026. [24] Salgia R,Stille JR,Weaver RW,et al. A randomized phase Ⅱ study of LY2510924 and carboplatin/etoposide versus carboplatin/etoposide in extensive-disease small cell lung cancer[J].Lung Cancer,2017,105:7-13.DOI:10.1016/ j.lungcan.2016.12.020. [25] Sanborn RE,Patel JD,Masters GA,et al. A randomized,double-blind,phase 2 trial of platinum therapy plus etoposide with or without concurrent vandetanib (ZD6474) in patients with previously untreated extensive-stage small cell lung cancer:hoosier cancer research network LUN06-113[J].Cancer,2017,123(2):303-311.DOI:10.1002/ cncr.30287. [26] Pietanza MC,Litvak AM,Varghese AM,et al. A phase I trial of the Hedgehog inhibitor,sonidegib (LDE225),in combination with etoposide and cisplatin for the initial treatment of extensive stage small cell lung cancer[J].Lung Cancer,2016,99:23-30.DOI:10.1016/j.lungcan.2016.04.014. [27] Reck M,Luft A,Szczesna A,et al. Phase Ⅲ randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer[J].J Clin Oncol,2016,34(31):3740-3748.DOI:10.1200/JCO.2016.67.6601. [28] Belani CP,Dahlberg SE,Rudin CM,et al. Vismodegib or cixutumumab in combination with standard chemotherapy for patients with extensive-stage small cell lung cancer:a trial of the ECOG-ACRIN cancer research group (E1508)[J].Cancer,2016,122(15):2371-2378.DOI:10.1002/cncr.30062. [29] Fukui T,Itabashi M,Ishihara M,et al. Prognostic factors affecting the risk of thoracic progression in extensive-stage small cell lung cancer[J].BMC Cancer,2016,16:197.DOI:10.1186/s12885-016-2222-4. [30] Gore EM,Hu C,Sun AY,et al. Randomized phase Ⅱ study comparing prophylactic cranial irradiation alone to prophylactic cranial irradiation and consolidative extracranial irradiation for extensive-disease small cell lung cancer (ED SCLC):NRG 0ncology RTOG 0937[J].J Thorac Oncol,2017,12(10):1561-1570.DOI:10.1016/j.jtho.2017.06.015. [31] Kim YH.Prophylactic cranial irradiation for extensive-stage small cell lung cancer[J].J Thorac Oncol,2016,11(12):e151-e152.DOI:10.1016/j.jtho.2016.08.148. [32] Maestu I,Pastor M,Gómez-Codina J,et al. Pretreatment prognostic factors for survival in small-cell lung cancer:A new prognostic index and validation of three known prognostic indices on 341 patients[J].Ann Oncol,1997,8(6):547–553. [33] Cerny T,Blair V,Anderson H,et al. Pretreatment prognostic factors and scoring system in 407 small-cell lung cancer patients[J].Int J Cancer,1987,39(2):146-149. [34] Albain KS,Crowley JJ,LeBlanc M,et al. Determinants of improved outcome in small-cell lung cancer:an analysis of the 2,580-patient southwest oncology group data base[J].J Clin Oncol,1990,8(9):1563-1574.DOI:10.1200/JCO.1990.8.9.1563. [35] Albain KS,Crowley JJ,LeBlanc M,et al. Survival determinants in extensive-stage non-small-cell lung cancer:the Southwest Oncology Group experience[J].J Clin Oncol,1991,9(9):1618-1626.DOI:10.1200/JCO.1991.9.9.1618. [36] Slotman BJ,Faivre-Finn C,van Tinteren H,et al. Which patients with ES-SCLC are most likely to benefit from more aggressive radiotherapy:A secondary analysis of the Phase Ⅲ CREST trial[J].Lung Cancer,2017,108(1):150-153. [37] Giuliani ME,Lindsay PE,Sun A,et al. Locoregional failures following thoracic irradiation in patients with limited-stage small cell lung carcinoma[J].Radiother Oncol,2012,102(2):263-267.DOI:10.1016/j.lungcan.2017.03.007. [38] Wu C,Li F,Jiao SC.Prognostic factors for survival of patients with extensive stage small cell lung cancer—a retrospective single institution analysis[J].Asian Pac J Cancer Prev,2012,13(10):4959-4962. [39] Kang EJ,Lee SY,Kim HJ,et al. Prognostic factors and skeletal-related events in patients with small cell lung cancer with bone metastases at the time of diagnosis[J].Oncology,2016,90(2):103-111.DOI:10.1159/000442949. [40] Hong X,Xu Q,Yang Z,et al. The value of prognostic factors in Chinese patients with small cell lung cancer:a retrospective study of 999 patients[J].Clin Respir J,2016 July27.DOI:10.1111/crj.12534 Epub ahead of print. [41] Ren Y,Dai C,Zheng H,et al. Prognostic effect of liver metastasis in lung cancer patients with distant metastasis[J].Oncotarget,2016,16;7(33):53245-53253.DOI:10.18632/oncotarget.10644. [42] Ogino H,Hanibuchi M,Kakiuchi S,et al. Analysis of the prognostic factors of extensive disease small-cell lung cancer patients in tokushima university hospital[J].J Med Invest,2016,63(3-4):286-93.DOI:10.2152/jmi.63.286. [43] Brower JV,Amini A,Chen S,et al. Improved survival with dose-escalated radiotherapy in stage Ⅲ non-small-cell lung cancer:analysis of the national cancer database[J].Ann Oncol,2016,27(10):1887-94.DOI:10.1093/annonc/ mdw276. [44] Jingu K,Matsuo Y,Onishi H,et al. Dose escalation improves outcome in stereotactic body radiotherapy for pulmonary oligometastases from colorectal cancer[J].Anticancer Res,2017,37(5):2709-2713.DOI:10.21873/anticanres.11621. [45] Chung SY,Chang JS,Lee BM,et al. Dose escalation in locally advanced pancreatic cancer patients receiving chemoradiotherapy[J].Radiother Oncol,2017,123(3):438-445.DOI:10.1016/j.radonc.2017.04.010. [46] Raziee H,Moraes FY,Murgic J,et al. Improved outcomes with dose escalation in localized prostate cancer treated with precision image-guided radiotherapy[J].Radiother Oncol,2017,123(3):459-465.DOI:10.1016/j.radonc.2017.04.003. [47] Zatloukal P,Cardenal F,Szczesna A,et al. A multicenter international randomized phase Ⅲ study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease[J].Ann Oncol,2010,21(9):1810-1816.DOI:10.1093/annonc/mdq036. [48] Spigel DR,Townley PM,Waterhouse DM,et al. Randomized phase Ⅱ study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer:results from the SALUTE trial[J].J Clin Oncol,2011,29(16):2215-2222.DOI:10.1200/JCO.2010.29.3423. [49] Laurie SA,Logan D,Markman BR,et al. Practice guideline for the role of combination chemotherapy in the initial management of limited-stage small-cell lung cancer[J].Lung Cancer,2004,43(2):223-240. [50] Socinski MA,Smit EF,Lorigan P,et al. Phase Ⅲ study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer[J].J Clin Oncol,2009,27(28):4787-4792.DOI:10.1200/JCO.2009.23.1548. [51] Lara PN Jr,Moon J,Redman MW,et al. Disease control rate at 8 weeks predicts subsequent survival in platinum-treated extensive stage small-cell lung cancer:results from the southwest oncology group (SWOG) database[J].Clin Lung Cancer,2016,17(2):113-118.DOI:10.1016/j.cllc.2015.09.003. [52] Chua YJ,Steer C,Yip D.Recent advances in management of small-cell lung cancer[J].Cancer Treat Rev,2004,30(6):521-543.DOI:10.1016/j.ctrv.2004.06.003. [53] Paesmans M,Sculier JP,Lecomte J,et al. Prognostic factors for patients with small cell lung carcinoma:analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years[J].Cancer,2000,89(3):523-533.