ﮐﺎرﺑﺮد ﻣﺪل ﺑﯿﻤﺎري - ﻣﺮگ ﺑﺮاي ﻣﺨﺎﻃﺮات ﻧﯿﻤﻪ رﻗﺎﺑﺘﯽ در ﺗﺤﻠﯿﻞ داده ﻫﺎي ﺳﺮﻃﺎن ﻣﻌﺪه

Application of Illness-Death Model for Semi-Competing Risks in Analysis Gastric Cancer Data

زﻣﯿﻨﻪ و ﻫﺪف: در ﻣﻄﺎﻟﻌﺎت ﺳﺮﻃﺎن، ﮔﺎﻫﯽ ﭘﯿﺸﺎﻣﺪﻫﺎ ﻧﯿﻤﻪ رﻗﺎﺑﺘﯽ ﻫﺴﺘﻨﺪ. در اﯾﻦ ﺣﺎﻟﺖ، ﻫﺮ ﺑﯿﻤﺎر ﺑﯿﺶ از ﯾﮏ ﭘﯿﺸﺎﻣﺪ را ﺗﺠﺮﺑﻪ ﻣﯽ ﮐﻨﺪ و ﺗﻨﻬﺎ ﯾﮑﯽ از آن ﭘﯿﺸﺎﻣﺪﻫﺎ ﺑﺮاي وي ﭘﯿﺸﺎﻣﺪ ﭘﺎﯾﺎﻧﯽ اﺳﺖ )ﺑﺮاي ﻣﺜﺎل، ﻣﺮگ( و ﺑﺎ رﺧﺪاد ﺳﺎﯾﺮ ﭘﯿﺸﺎﻣﺪﻫﺎي ﻏﯿﺮﭘﺎﯾﺎﻧﯽ ﺑﺮاي ﻣﺜﺎل، ﻋﻮد ﺑﯿﻤﺎري( رﻗﺎﺑﺖ ﻣﯽ ﮐﻨﺪ. اﯾﻦ ﻣﻄﺎﻟﻌﻪ ﺑﺎ ﻫﺪف ﺗﻌﯿﯿﻦ اﺛﺮ ﻋﻮاﻣﻞ ﺧﻄﺮ روي زﻣﺎن ﻋﻮد، زﻣﺎن ﻣﺮگ ﺑﺪون ﻋﻮد و زﻣﺎن ﻣﺮگ ﭘﺲ از ﻋﻮد ﺑﯿﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﺳﺮﻃﺎن ﻣﻌﺪه ﺑﺎ اﺳﺘﻔﺎده از ﻣﺪل ﺑﯿﻤﺎري - ﻣﺮگ اﻧﺠﺎم ﺷﺪه اﺳﺖ. ﻣﻮاد و روش ﻫﺎ: اﯾﻦ ﻣﻄﺎﻟﻌﻪ ﯾﮏ ﻣﻄﺎﻟﻌﻪ ﻫﻢﮔﺮوه ﺗﺎرﯾﺨﯽ ﺑﻮد ﮐﻪ در آن از دادهﻫﺎي 200 ﺑﯿﻤﺎر ﻣﺒﺘﻼ ﺑﻪ ﺳﺮﻃﺎن ﻣﻌﺪه، ﻣﺮاﺟﻌﻪ ﮐﻨﻨﺪه ﺑﻪ ﺑﯿﻤﺎرﺳﺘﺎن اﻣﺎم ﺧﻤﯿﻨﯽ ﻃﯽ ﺳﺎلﻫﺎي 1382 ﺗﺎ 1386، اﺳﺘﻔﺎده ﺷﺪ ﮐﻪ ﺗﺎ ﺳﺎل 1388 ﭘﯿﮕﯿﺮي ﺷﺪﻧﺪ. ﺑﺮاي ﺗﺤﻠﯿﻞ دادهﻫﺎ از ﻣﺪل ﺑﯿﻤﺎري - ﻣﺮگ، ﺑﺎ و ﺑﺪون ﺷﮑﻨﻨﺪﮔﯽ ﻣﺸﺘﺮك و ﺑﺎ ﻓﺮض ﻧﯿﻤﻪ ﻣﺎرﮐﻒ، اﺳﺘﻔﺎده ﮔﺮدﯾﺪ. آﻧﺎﻟﯿﺰ داده ﻫﺎ ﺑﺎ اﺳﺘﻔﺎده از ﻧﺮم اﻓﺰار 3 -4-3 R اﻧﺠﺎم ﺷﺪ. ﯾﺎﻓﺘﻪ ﻫﺎ: 61 ﻧﻔﺮ )30/5 درﺻﺪ( از اﻓﺮاد ﻣﻮرد ﻣﻄﺎﻟﻌﻪ داراي ﻋﻮد، 71 ﻧﻔﺮ )35/5 درﺻﺪ( ﻣﺮگ، 27 ﻧﻔﺮ )13 درﺻﺪ( ﻋﻮد و ﻣﺮگ، 34 ﻧﻔﺮ )17 درﺻﺪ( ﻋﻮد ﺑﺪون ﻣﺮگ و 44 ﻧﻔﺮ )22 درﺻﺪ( ﻣﺮگ ﺑﺪون ﻋﻮد داﺷﺘﻨﺪ. در ﺗﺤﻠﯿﻞ ﭼﻨﺪ ﻣﺘﻐﯿﺮه، ﻓﺎﺻﻠﻪ ﻫﺎي اﻃﻤﯿﻨﺎن ﺑﻪ دﺳﺖ آﻣﺪه ﻧﺸﺎن دادﻧﺪ ﮐﻪ ﻣﺘﻐﯿﺮ ﺗﻌﺪاد ﻏﺪد ﻟﻨﻔﺎوي روي زﻣﺎن ﻋﻮد، ﻣﺘﺎﺳﺘﺎز روي زﻣﺎن ﻣﺮگ ﺑﺪون ﻋﻮد و ﻣﺮﺣﻠﻪ ﺑﯿﻤﺎري روي زﻣﺎن ﻣﺮگ ﭘﺲ از ﻋﻮد اﺛﺮ ﻣﻌﻨﯽ دار داﺷﺘﻨﺪ. ﻧﺘﯿﺠﻪ ﮔﯿـﺮي: ﺑﺮآورد اﺛﺮ ﻣﺘﻐﯿﺮﻫﺎ در ﻣﺮاﺣﻞ ﻣﺨﺘﻠﻒ ﻣﺘﻔﺎوت ﺑﺪﺳﺖ آﻣﺪ. ﺑﻪ ﻋﺒﺎرﺗﯽ، اﺛﺮ ﻋﻮاﻣﻞ ﺧﻄﺮ روي زﻣﺎن ﻣﺮگ ﺑﯿﻤﺎران ﻗﺒﻞ و ﺑﻌﺪ از ﭘﯿﺸﺎﻣﺪ ﻋﻮد ﻣﺘﻔﺎوت ﺑﻮد. ﺑﻨﺎﺑﺮاﯾﻦ ﭘﯿﺸﺎﻣﺪ ﻋﻮد ﺑﻪ ﻋﻨﻮان ﯾﮏ ﭘﯿﺸﺎﻣﺪ ﻣﯿﺎﻧﯽ ﻣﻬﻢ ﺗﻠﻘﯽ ﺷﺪه و ﺑﺎﯾﺪ ﻣﻮرد ﺗﻮﺟﻪ درﻣﺎن ﮔﺮان ﻗﺮار ﮔﯿﺮد.

Introduction & Objective: In cancer studies, sometimes events are semi-competing. In this case, each patient experiences more than one event, and only one of those is a terminal event (for example, death), and others are non-terminal events (for example, relapse of the disease after treatment) where the risk of death competes with the risk of a non-terminal event of relapse but not vice versa. The aim of this study was to determine the effect of risk factors on relapse time, death time without relapse, and death time after relapse in gastric cancer patients using an illness-death model. Materials & Methods: In this historical cohort study, 200 patients with gastric cancer were studied. These patients had referred to Imam Khomeini hospital 2003 - 2007 and were followed up to October 2009. The data was analyzed by illness-death model, with and without frailty by considering semi-Markov assumption in R 3.4.3 software. Results: Of the patients, 61 (30.5%) had relapses, 71 (35.5%) deaths, 27 (13%) relapsed and death, 34 (17%) relapsed without death and 44 (22%) was died without relapsed. In multivariate analysis, based on confidence intervals, the lymph nodes had a significant effect on the relapse time; metastasis had a significant effect on the time of death without relapse and stage of disease had a significant effect on the death time after relapse. Conclusions: Estimates of the effect of variables were different at the stages in the model. In other words, the effect of risk factors on the time of death was different before and after of relapse occurrence. Therefore, the relapse event as an intermediate event is very important and should be considered by therapists.