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4๊ธฐ ์œ„์•”์—์„œ ์ˆ˜์ˆ ์  ์น˜๋ฃŒ์˜ ์—ญํ• 

Abstract

Surgery plays a key role in gastric cancer treatment without distant metastasis. However, once distant sites are involved, no optimal therapeutic strategy has been established. Because M1 gastric cancer is a heterogeneous disease entity according to the extent and site of metastasis, it is difficult to analyze and interpret the result of study subjected to relative small number of patients. In patients without symptoms, several studies have shown that reductive surgery might have a benefit in terms of survival and quality of life. A randomized controlled trial of reduction surgery plus chemotherapy versus chemotherapy alone for M1 gastric cancer is ongoing (REductive Gastrectomy for Advanced Tumor in Three Asian countries [REGATTA], JCOG0705/KGCA01), and the result would be reported in near future. Currently, as an initial treatment for M1 gastric cancer, chemotherapy is generally used in order to reduce tumor-related symptom and prolong survival. For patients responsive to chemotherapy, some retrospective studies reported that longer survival was observed in resection group after disappearing of distant metastasis. Recently, Japanese group reported that a multimodality treatment consisting of chemotherapy with S-1 and cisplatin followed by gastrectomy with D2+ para-aortic lymph node dissection was found to be promising for metastasis to the 16a1/b2 para-aortic lymph nodes.

์„œ ๋ก 

์œ„์•”์€ ์„ธ๊ณ„์—์„œ 5๋ฒˆ์งธ๋กœ ๋ฐœ์ƒ ๋นˆ๋„๊ฐ€ ๋†’์€ ์•”์ด๋ฉฐ 3๋ฒˆ์งธ๋กœ ์‚ฌ๋ง๋ฅ ์ด ๋†’์€ ์•”์ด๋‹ค[1]. ํ•œ๊ตญ์—์„œ๋Š” ํ˜„์žฌ ๊ฐ‘์ƒ์„ ์•”์— ์ด์–ด 2๋ฒˆ์งธ๋กœ ๋ฐœ์ƒ ๋นˆ๋„๊ฐ€ ๋†’์€ ์•”์ด๋ฉฐ, ๊ตญ๊ฐ€ ์กฐ๊ธฐ ๊ฑด๊ฐ• ๊ฒ€์ง„์— ํšจ๊ณผ๋กœ ์กฐ๊ธฐ์œ„์•”์˜ ๋นˆ๋„๊ฐ€ ์ ์  ๋Š˜์–ด๋‚˜๊ณ  ์žˆ์œผ๋‚˜, ์ง„๋‹จ ์‹œ ์›๊ฒฉ ์ „์ด๋ฅผ ๋™๋ฐ˜ํ•œ ๊ฒฝ์šฐ๋„ 6.3%โ€“9.0%์— ์ด๋ฅธ๋‹ค[2,3]. D1+ ๋˜๋Š” D2 ๊ตฌ์—ญ ๋ฆผํ”„์ ˆ ์ ˆ์ œ๋ฅผ ํฌํ•จํ•œ ๊ทผ์น˜์  ์ ˆ์ œ๊ฐ€ ์œ„์•” ์น˜๋ฃŒ์˜ ๊ทผ๊ฐ„์„ ์ด๋ฃจ๋‚˜, ์›๊ฒฉ ์ „์ด๋ฅผ ๋™๋ฐ˜ํ•œ M1 ์œ„์•”์˜ ๊ฒฝ์šฐ ์•„์ง ์›์น™์ ์ธ ์น˜๋ฃŒ ๋ฐฉ์นจ์ด ์ •ํ•ด์ ธ ์žˆ์ง€ ์•Š์€ ์ƒํƒœ์ด๋‹ค.
์ผ๋ฐ˜์ ์œผ๋กœ M1 ์œ„์•”์˜ ์ผ์ฐจ ์น˜๋ฃŒ๋กœ, ์•”์œผ๋กœ ์ธํ•œ ์ฆ์ƒ ์™„ํ™” ๋ฐ ์ƒ์กด ์—ฐ์žฅ์„ ๋ชฉ์ ์œผ๋กœ ํ•ญ์•”ํ™”ํ•™ ์š”๋ฒ•์„ ์‹œํ–‰ํ•˜๋Š”๋ฐ, 1990๋…„๋Œ€ 5-FU ๋‹จ์ผ ์š”๋ฒ•๊ณผ 5-FU๋ฅผ ๊ธฐ๋ณธ์œผ๋กœ ํ•˜๋Š” ๋ณ‘ํ•ฉ์š”๋ฒ•์— ๋Œ€ํ•œ ๋น„๊ต ์—ฐ๊ตฌ๊ฐ€ ์‹œํ–‰๋˜์—ˆ์œผ๋ฉฐ, 5-FU+cisplatin ๋ณ‘ํ•ฉ ๊ตฐ์—์„œ 7.2โ€“8.5๊ฐœ์›”์˜ ์ค‘์•™ ์ƒ์กด๊ธฐ๊ฐ„์ด ๊ด€์ฐฐ๋˜์—ˆ๋‹ค[4,5]. ์ดํ›„ 5-FU, cisplatin์— Docetaxel์„ ์ถ”๊ฐ€ํ•œ ์—ฐ๊ตฌ์—์„œ 9.2๊ฐœ์›”์˜ ์ค‘์•™ ์ƒ์กด๊ธฐ๊ฐ„์ด[6], JCOG9912 ์—ฐ๊ตฌ์—์„œ๋Š” S-1 ๋‹จ์ผ ์š”๋ฒ•์œผ๋กœ 11.4๊ฐœ์›”์˜ ์ค‘์•™ ์ƒ์กด๊ธฐ๊ฐ„์ด ๊ด€์ฐฐ ๋˜์—ˆ๋‹ค[7]. ์ตœ๊ทผ ์ „ํ†ต์ ์ธ ํ•ญ์•”์ œ์— ๋‹จํด๋ก  ํ•ญ์ฒด๋ฅผ ์ถ”๊ฐ€ํ•œ ํ‘œ์  ์น˜๋ฃŒ๋กœ ์ค‘์•™ ์ƒ์กด๊ธฐ๊ฐ„์€ 13.8๊ฐœ์›”๋กœ ์—ฐ์žฅ๋˜์—ˆ๋‹ค[8].
์›๊ฒฉ ์ „์ด๋ฅผ ๋™๋ฐ˜ํ•˜์ง€ ์•Š์€ ์œ„์•”์—์„œ, ๋ณ‘๊ธฐ๋ฅผ ๋‚ฎ์ถ”๊ณ , ๊ทผ์น˜์  ์ ˆ์ œ๋ฅผ ๊ฐ€๋Šฅํ•˜๊ฒŒ ํ•˜๊ธฐ ์œ„ํ•ด์„œ ์„ ํ–‰ํ™”ํ•™์š”๋ฒ•(neoadjuvant chemotherapy)๋ฅผ ์‹œํ–‰ํ•˜๊ธฐ๋„ ํ•˜๋ฉฐ, ์„ ํ–‰ ํ™”ํ•™ ์š”๋ฒ• ํ›„ ๊ทผ์น˜์  ์ ˆ์ œ๋ฅผ ์‹œํ–‰ํ•  ๊ฒฝ์šฐ ์ƒ์กด์œจ์˜ ํ–ฅ์ƒ ๋œ๋‹ค๋Š” ๋ณด๊ณ ๊ฐ€ ์žˆ๋‹ค[9,10]. ํ•˜์ง€๋งŒ M1 ์œ„์•”์—์„œ๋Š” ์ˆ˜์ˆ ์ด ์ƒ์กด์œจ์„ ํ–ฅ์ƒ์‹œํ‚ฌ ์ˆ˜ ์žˆ๋Š”์ง€์— ๋Œ€ํ•œ ์—ฐ๊ตฌ๊ฐ€ ๋งค์šฐ ํ•œ์ •์ ์ด๋‹ค. M1 ์œ„์•”์˜ ์น˜๋ฃŒ๋Š” NCCN ๊ฐ€์ด๋“œ๋ผ์ธ์—์„œ๋Š”, ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•, ์ž„์ƒ์—ฐ๊ตฌ, ๋˜๋Š” ์ตœ์„ ์˜ ์ง€์ง€์น˜๋ฃŒ(best supportive care)์ด๋ฉฐ, ์ผ๋ณธ์œ„์•”ํ•™ํšŒ์˜ ์น˜๋ฃŒ ๊ฐ€์ด๋“œ๋ผ์ธ์—์„œ๋Š”, ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•, ๋ฐฉ์‚ฌ์„ ์น˜๋ฃŒ, ๊ณ ์‹์  ์ˆ˜์ˆ  ๋˜๋Š” ์˜๋ฃŒํ–‰์œ„๋กœ ์ œ์‹œํ•˜๊ณ  ์žˆ๋‹ค[11,12].
M1 ์œ„์•”์ด ์ถœํ˜ˆ ๋ฐ ํ์ƒ‰์„ ๋™๋ฐ˜ํ•œ ๊ฒฝ์šฐ ์ฆ์ƒ ์™„ํ™”๋ฅผ ๋ชฉ์ ์œผ๋กœ, ๋‚ด์‹œ๊ฒฝ์  ์‹œ์ˆ , ๋ฐฉ์‚ฌ์„  ์ค‘์žฌ์‹œ์ˆ  ๋˜๋Š” ๊ณ ์‹์  ์ˆ˜์ˆ ์„ ์‹œํ–‰ํ•˜๊ฒŒ ๋˜๋Š”๋ฐ, ๊ณ ์‹์  ์ˆ˜์ˆ ์— ๋Œ€ํ•ด ์ด๋ฒˆ ์ข…์„ค์—์„œ๋Š” ๋…ผ์™ธ๋กœ ํ•˜๊ธฐ๋กœ ํ•œ๋‹ค. ์ด๋ฒˆ ์ข…์„ค์—์„œ๋Š” M1 ์œ„์•” ํ™˜์ž์—์„œ ์ƒ์กด์œจ ํ–ฅ์ƒ์„ ์œ„ํ•ด ์ˆ˜์ˆ ์  ์น˜๋ฃŒ๊ฐ€ ์–ด๋– ํ•œ ์—ญํ• ์„ ํ•  ์ˆ˜ ์žˆ๋Š”์ง€์— ๋Œ€ํ•ด ๋ฌธํ—Œ ๊ณ ์ฐฐ์„ ํ†ตํ•ด ์•Œ์•„๋ณด๊ณ ์ž ํ•œ๋‹ค.

๋ณธ ๋ก 

Reduction surgery

์ถœํ˜ˆ ๋˜๋Š” ํ์ƒ‰์˜ ์ฆ์ƒ์ด ์—†๋Š” M1 ์œ„์•”์—์„œ, ํ•ญ์•”์น˜๋ฃŒ ์ „์— ์•”์ข…์˜ ๋ถ€ํ”ผ๋ฅผ ์ค„์—ฌ ์ƒ์กด์œจ ํ–ฅ์ƒ์„ ๋„๋ชจํ•˜๋ ค๋Š” ์ˆ˜์ˆ ์„ reduction surgery๋ผ๊ณ  ํ•œ๋‹ค. ๋งŽ์€ ํ›„ํ–ฅ์  ์—ฐ๊ตฌ๊ฐ€ reduction surgery์„ ์‹œํ–‰ํ•˜๋Š” ๊ฒƒ์ด ์ƒ์กด์œจ ๋ฐ ์‚ถ์˜ ์งˆ์„ ํ–ฅ์ƒ์‹œํ‚ค๊ณ , ์ฆ์ƒ์„ ์™„ํ™”์‹œํ‚จ๋‹ค๊ณ  ๋ณด๊ณ ํ•˜๊ณ  ์žˆ๋‹ค[13-15]. Hartgrink ๋“ฑ[16]์€, 70์„ธ ๋ฏธ๋งŒ์˜ ํ™˜์ž์—์„œ ์ „์ด๊ฐ€ ํ•œ ๊ณณ์— ๊ตญํ•œ๋˜์–ด ์žˆ์„ ๊ฒฝ์šฐ, reduction surgery ์‹œํ–‰ ๊ตฐ์ด ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•๋งŒ ์‹œํ–‰ํ•œ ๊ตฐ์— ๋น„ํ•ด ๊ธด ์ค‘์•™ ์ƒ์กด๊ธฐ๊ฐ„(10.5๊ฐœ์›” vs. 6.7๊ฐœ์›”, P=0.034)์„ ๋ณด์ธ๋‹ค๊ณ  ๋ณด๊ณ ํ•˜์˜€๋‹ค. Chang ๋“ฑ[17]์€, ์ „์ด๊ฐ€ ํ•œ ๊ณณ์— ๊ตญํ•œ๋˜์–ด ์žˆ์„ ๊ฒฝ์šฐ, reduction surgery ์‹œํ–‰ ํ›„ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์„ ์‹œํ–‰ํ•œ ๊ตฐ์—์„œ ๊ธด ์ค‘์•™ ์ƒ์กด๊ธฐ๊ฐ„(14.0๊ฐœ์›” vs. 9.7๊ฐœ์›”, P=0.040)์„ ๋ณด์˜€์œผ๋ฉฐ, ๋‘ ๊ณณ ์ด์ƒ์— ์ „์ด๊ฐ€ ์ง„ํ–‰๋˜์—ˆ์„ ๊ฒฝ์šฐ ์ค‘์•™ ์ƒ์กด๊ธฐ๊ฐ„(10.2๊ฐœ์›” vs. 11.2๊ฐœ์›”, P=0.400)์— ์ฐจ์ด๊ฐ€ ์—†๋‹ค๊ณ  ๋ณด๊ณ ํ•˜์˜€๋‹ค. ๋งŽ์€ ์—ฐ๊ตฌ์—์„œ reduction surgery ํ›„ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์„ ์‹œํ–‰ํ•œ ๊ตฐ์ด ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•๋งŒ ์‹œํ–‰ํ•œ ๊ตฐ์— ๋น„ํ•ด ์ƒ์กด์œจ ํ–ฅ์ƒ์ด ๊ด€์ฐฐ๋˜๊ณ  ์žˆ์œผ๋‚˜ ์„ ํƒ ๋น„๋šค๋ฆผ(selection bias)์ด ์ž‘์šฉํ•  ์—ฌ์ง€๊ฐ€ ๋งŽ๋‹ค.
์ตœ๊ทผ ํ•œ ๊ฐœ์˜ ๋น„์น˜์œ  ์ธ์ž(๊ฐ„์ „์ด, ๋ณต๋ง‰์ „์ด, 16a1/b2 ๋Œ€๋™๋งฅ๋ฆผํ”„์ ˆ์ „์ด)๋ฅผ ๊ฐ€์ง„ M1 ์œ„์•”์—์„œ reduction surgery ํ›„ ์ƒ์กด์œจ์ด ํ–ฅ์ƒ๋˜๋Š”์ง€ ์•Œ์•„๋ณด๊ณ ์ž ํ•˜๋Š” REductive Gastrectomy for Advanced Tumor in Three Asian countries (REGATTA) ์—ฐ๊ตฌ(JCOG0705/KGCA01)๊ฐ€ ์‹œํ–‰๋˜์—ˆ๋‹ค(Fig. 1) [18]. ์•„์ง ์ตœ์ข… ๊ฒฐ๊ณผ๋Š” ๋‚˜์˜ค์ง€ ์•Š์€ ์ƒํƒœ์ด๋ฉฐ reduction surgery์˜ ํšจ์šฉ์— ๋Œ€ํ•ด ๋ช…ํ™•ํ•œ ๊ฒฐ๋ก ์„ ๋‚ด๋ ค์ค„ ์—ฐ๊ตฌ๋ผ ์ƒ๊ฐ๋œ๋‹ค.

Conversion surgery

Conversion surgery๋Š” M1 ์œ„์•”์—์„œ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ• ์‹œํ–‰์ค‘, ์ „์ด์•”์˜ ๊ด€ํ•ด๊ฐ€ ๋‚˜ํƒ€๋‚œ ํ›„ ์™„์ „ ์ ˆ์ œ๋ฅผ ๋ชฉ์ ์œผ๋กœ ์œ„์ ˆ์ œ๋ฅผ ์‹œํ–‰ํ•˜๋Š” ๊ฒƒ์„ ์˜๋ฏธํ•œ๋‹ค. Conversion surgery๋ฅผ ์‹œํ–‰ํ•˜๊ธฐ ์œ„ํ•ด์„œ๋Š” ์ „์ด์•”์ด ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์— ์˜ํ•ด ์™„์ „ ๊ด€ํ•ด๊ฐ€ ๋˜์—ˆ๋‹ค๋Š” ์ „์ œ๊ฐ€ ํ•„์š”ํ•˜๋ฉฐ, ๋”ฐ๋ผ์„œ ์ดˆ๊ธฐ์— ๋ฐœ๊ฒฌ๋˜์—ˆ๋˜ ๋ชจ๋“  ์•” ๋ณ‘์†Œ๋ฅผ ์ ˆ์ œํ•˜๋Š” ๊ฒƒ์€ ์•„๋‹ˆ๋‹ค.
Han ๋“ฑ[19]์€ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ• ํ›„ ์ „์ด์•”์˜ ๊ด€ํ•ด๋ฅผ ๋ณด์—ฌ ์™„์น˜๋ชฉ์ (curative intent)๋กœ ์ˆ˜์ˆ ์„ ์‹œํ–‰ํ•œ 34์˜ˆ๋ฅผ ๋Œ€์ƒ์œผ๋กœ ํ•œ ์—ฐ๊ตฌ๋ฅผ ๋ณด๊ณ ํ•˜์˜€๋‹ค. 76.5%์—์„œ R0 ์ ˆ์ œ๊ฐ€ ๊ฐ€๋Šฅํ•˜์˜€์œผ๋‚˜ R0 ์ ˆ์ œ ํ›„ 61.5%์—์˜ ์žฌ๋ฐœ๋ฅ ์„ ๋ณด์˜€์œผ๋ฉฐ, ์ถ”์ ๊ด€์ฐฐ๊ธฐ๊ฐ„ ๋™์•ˆ 38.5%์˜ ํ™˜์ž๊ฐ€ ๋ฌด๋ณ‘์ƒํƒœ์˜€๋‹ค. ํŠนํžˆ ๋ฌด๋ณ‘์ƒํƒœ์ธ ํ™˜์ž์˜ 90%๋Š” ํ•ญ์•”ํ™”ํ•™์š”๋ฒ• ์ „ ์ „์ด๊ฐ€ ํ•œ ๊ณณ์— ๊ตญํ•œ๋˜์–ด ์žˆ๋˜ ํ™˜์ž๋“ค์ด์—ˆ๋‹ค. Kitayama ๋“ฑ[20]์€ 64๋ช…์˜ ๋ณต๋ง‰์ „์ด ์œ„์•”์— ๋Œ€ํ•ด S1, paclitaxel ํ•ญ์•”ํ™”ํ•™์š”๋ฒ• ๋ฐ ๋ณต๊ฐ•๋‚ด paclitaxel ํˆฌ์—ฌ๋ฅผ ์‹œํ–‰ํ•˜์˜€๊ณ , 34๋ช…์˜ ํ™˜์ž์—์„œ ๋ณต๋ง‰์ „์ด์˜ ๊ด€ํ•ด๋ฅผ ๋ณด์—ฌ ์œ„์ ˆ์ œ๋ฅผ ์‹œํ–‰ํ•˜์˜€๋‹ค. ์œ„์ ˆ์ œ๋ฅผ ์‹œํ–‰ํ•œ ๊ตฐ์€ ์ค‘์•™ ์ƒ์กด๊ธฐ๊ฐ„ 26.4๊ฐœ์›”๋กœ ์‹œํ–‰ํ•˜์ง€ ์•Š์€ ๊ตฐ์˜ 12.1๊ฐœ์›”์— ๋น„ํ•ด ์œ ์˜ํ•œ ์ฐจ์ด๋ฅผ ๋ณด์˜€๋‹ค. Fukuchi ๋“ฑ[21]์€ S1+cisplatin ๋˜๋Š” paclitaxel ํ•ญ์•”์š”๋ฒ•ํ›„ conversion surgery๋ฅผ ์‹œํ–‰ํ•œ 40์˜ˆ๋ฅผ ๋ถ„์„ํ•˜์˜€์œผ๋ฉฐ, ์œ„์ ˆ์ œ๋ฅผ ์‹œํ–‰ํ•œ ๊ตฐ์—์„œ ๊ธด ์ค‘์•™ ์ƒ์กด๊ธฐ๊ฐ„(53๊ฐœ์›” vs. 14๊ฐœ์›”, P<0.01)์„ ๋ณด์˜€๋‹ค. Wang ๋“ฑ[22]์€ 16a2/b1 ๋Œ€๋™๋งฅ ๋ฆผํ”„์ ˆ ์ „์ด๊ฐ€ ์žˆ๋Š” 48๋ช…์˜ ํ™˜์ž๋ฅผ ๋Œ€์ƒ์œผ๋กœ XELOX ์š”๋ฒ• ํ›„ ๋Œ€๋™๋งฅ ๋ฆผํ”„์ ˆ์˜ ๊ด€ํ•ด๊ฐ€ ๋‚˜ํƒ€๋‚œ 28๋ช…์˜ ํ™˜์ž์—์„œ D2 ์œ„์ ˆ์ œ๋ฅผ ์‹œํ–‰ํ•˜์˜€์œผ๋ฉฐ ์ˆ˜์ˆ ๊ตฐ์—์„œ์˜ ๋†’์€ ์ƒ์กด์œจ์˜ ๋ณด๊ณ ํ•˜์˜€๋‹ค.
M1 ์œ„์•”์—์„œ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ• ์‹œํ–‰ ํ›„ ์ „์ด์•”์˜ ๊ด€ํ•ด๊ฐ€ ๋‚˜ํƒ€๋‚œ ํ›„ conversion surgery๋ฅผ ์‹œํ–‰ํ•  ๊ฒฝ์šฐ ์ƒ์กด๊ธฐ๊ฐ„์„ ์—ฐ์žฅํ•  ์ˆ˜ ์žˆ์Œ์ด ์—ฌ๋Ÿฌ ํ›„ํ–ฅ์  ์—ฐ๊ตฌ์—์„œ ๋ณด๊ณ ๋˜์—ˆ์œผ๋ฉฐ, ํŠนํžˆ ์ „์ด์•”์ด ํ•œ ๊ณณ์— ๊ตญํ•œ๋˜์–ด ์žˆ๋Š” ๊ฒฝ์šฐ ๋” ์ข‹์€ ์˜ˆํ›„๋ฅผ ๋ณด์˜€๋‹ค. ํ•˜์ง€๋งŒ ์ „์ด์•”์˜ ๊ด€ํ•ด๊ฐ€ ์ด๋ฃจ์–ด์ง„ ์ƒํƒœ์—์„œ ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์„ ์ง€์†ํ•˜๋Š” ๊ฒƒ๊ณผ conversion surgery๋ฅผ ์‹œํ–‰ํ•˜๋Š” ๊ฒƒ์— ๋Œ€ํ•œ ๋น„๊ต์—ฐ๊ตฌ๋Š” ์—†๋Š” ์ƒํƒœ์ด๋ฉฐ, ํ–ฅํ›„ ์ด ๋ถ€๋ถ„์— ๋Œ€ํ•œ ์—ฐ๊ตฌ๊ฐ€ ํ•„์š”ํ•˜๋‹ค๊ณ  ์ƒ๊ฐ๋œ๋‹ค.

D2+๋Œ€๋™๋งฅ๋ฆผํ”„์ ˆ ์ ˆ์ œ

Conversion surgery์™€๋Š” ๋‹ค๋ฅด๊ฒŒ D2+๋Œ€๋™๋งฅ๋ฆผํ”„์ ˆ ์ ˆ์ œ๋Š” ํ•ญ์•”ํ™”ํ•™ ์š”๋ฒ•์ด ์•”์„ธํฌ์˜ ๋ฏธ์†Œ์ „์ด(micrometastasis)๋Š” ์ค„์ผ ์ˆ˜ ์žˆ์–ด๋„ ์ „์ด์•” ์ž์ฒด(gross tumor)๋Š” ์น˜์œ ํ•˜์ง€ ๋ชปํ•จ์„, ๊ทธ๋ฆฌ๊ณ  16a2/b1 ๋Œ€๋™๋งฅ ๋ฆผํ”„์ ˆ์ด ์ ˆ์ œ ๊ฐ€๋Šฅํ•˜๋‹ค๋Š” ๊ฒƒ์„ ์ „์ œ๋กœ ํ•œ๋‹ค. ๋Œ€๋™๋งฅ๋ฆผํ”„์ ˆ ์ „์ด๊ฐ€ ์žˆ๋Š” ๊ฒฝ์šฐ, ์—ฌ๋Ÿฌ Japanese Clinical Oncology Group (JCOG) ์—ฐ๊ตฌ๊ฐ€ ํ•ญ์•” ์น˜๋ฃŒ ํ›„์—, D2+๋Œ€๋™๋งฅ๋ฆผํ”„์ ˆ์„ ๋™๋ฐ˜ํ•œ ์œ„์ ˆ์ œ์— ๋Œ€ํ•ด ๋ณด๊ณ ํ•˜์˜€๋‹ค. ์ด๋“ค์€ bulky N2/N3 ๋ฆผํ”„์ ˆ ์ „์ด๊ฐ€ ์žˆ๋Š” ์œ„์•”์„ ๋Œ€์ƒ์œผ๋กœ ํ•œ 2์ƒ ์—ฐ๊ตฌ์ด๋ฉฐ, bulky N2/N3์˜ ์ •์˜๋Š” ๋‹ค์Œ ์ค‘ ํ•˜๋‚˜์— ํ•ด๋‹นํ•˜๋Š” ๊ฒฝ์šฐ์ด๋‹ค: (1) 3 cm ์ด์ƒ ํฌ๊ธฐ์˜ ํ•œ ๊ฐœ ์ด์ƒ์˜ ๋ฆผํ”„์ ˆ(No. 7, 8, 9, 11), (2) 1 cm ์ด์ƒ ํฌ๊ธฐ์˜ ์ธ์ ‘ํ•œ 3๊ฐœ ์ด์ƒ์˜ ๋ฆผํ”„์ ˆ(No. 7, 8, 9, 11), (3) 1 cm ์ด์ƒ ํฌ๊ธฐ์˜ ๋Œ€๋™๋งฅ๋ฆผํ”„์ ˆ(No. 16a2/b1) [23]. JCOG0001 ์—ฐ๊ตฌ๋Š” bulky N2/N3 ์œ„์•”์„ ๋Œ€์ƒ์œผ๋กœ irinotecan๊ณผ cisplatin์„ ์‚ฌ์šฉํ•˜์˜€์œผ๋ฉฐ, R0 ์ ˆ์ œ์œจ์€ 65%์˜€๊ณ  3๋…„ ์ƒ์กด์œจ์€ 15% ์˜€๋‹ค[24]. JCOG0405 ์—ฐ๊ตฌ๋Š” S1+-cisplatin ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์„ ์‚ฌ์šฉํ•˜์˜€์œผ๋ฉฐ, 82%์˜ R0 ์ ˆ์ œ์œจ ๋ฐ 59%์˜ 3๋…„ ์ƒ์กด์œจ์„ ๋ณด์˜€๋‹ค[25]. ๋˜ํ•œ bulky N2/N3 ์œ„์•”์„ ๋Œ€์ƒ์œผ๋กœ S1+-cisplatin+docetaxel ํ•ญ์•”ํ™”ํ•™์š”๋ฒ• ํ›„ D2+๋Œ€๋™๋งฅ๋ฆผํ”„์ ˆ ์ ˆ์ œ๋ฅผ ์‹œํ–‰ํ•˜๋Š” JCOG1002 ์—ฐ๊ตฌ๊ฐ€ ์ง„ํ–‰ ์ค‘์— ์žˆ๋‹ค[26].
๋น„๋ก ์ˆ˜๊ฐ€ ํ•œ์ •๋˜์–ด ์žˆ๊ณ  ์„ ํƒ ๋น„๋šค๋ฆผ์ด ์ž‘์šฉํ•  ์—ฌ์ง€๊ฐ€ ์žˆ์ง€๋งŒ, ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์— ์ด์€ D2+๋Œ€๋™๋งฅ๋ฆผํ”„์ ˆ ์ ˆ์ œ๋กœ ์ƒ์กด์œจ์„ ํ–ฅ์ƒ์‹œํ‚ฌ ์ˆ˜ ์žˆ์Œ์ด ์—ฌ๋Ÿฌ 2์ƒ ์—ฐ๊ตฌ์—์„œ ๋ณด๊ณ ๋˜๊ณ  ์žˆ๋‹ค. ํ˜„์žฌ ๋‹ค๋ฅธ ์›๊ฒฉ์ „์ด๊ฐ€ ์—†๋Š” 16a2/b1 ๋Œ€๋™๋งฅ ๋ฆผํ”„์ ˆ ์ „์ด๋Š” ๊ฒฝ๊ณ„์„ฑ ์ ˆ์ œ๊ฐ€๋Šฅ ์•”(borderline resectable cancer)๋กœ ๊ฐ„์ฃผํ•  ์ˆ˜ ์žˆ์œผ๋ฉฐ, ์น˜๋ฃŒ๋ฐฉ์นจ์— ๋”ฐ๋ผ conversion surgery ๋˜๋Š” D2+๋Œ€๋™๋งฅ๋ฆผํ”„์ ˆ ์ ˆ์ œ๋ฅผ ์‹œํ–‰ํ•ด๋ณผ ์ˆ˜ ์žˆ๊ฒ ๋‹ค[27].

๊ฐ„์ „์ด์˜ ์ˆ˜์ˆ ์  ์ ˆ์ œ

์œ„์•”์˜ ๊ฐ„์ „์ด๋Š” ์ผ๋ฐ˜์ ์œผ๋กœ ๊ฐ„์˜ ์–‘์ธก์„ ์นจ๋ฒ”ํ•˜๋Š” ๋‹ค๋ฐœ์„ฑ ์ „์ด๋กœ ๋‚˜ํƒ€๋‚˜๊ณ  ๊ฐ„ ์™ธ ์ „์ด๋ฅผ ๋™๋ฐ˜ํ•˜๋Š” ๊ฒฝ์šฐ๊ฐ€ ๋งŽ๊ธฐ ๋•Œ๋ฌธ์— ์ˆ˜์ˆ ์˜ ์ ์‘์ฆ์ด ๋˜๋Š” ๊ฒฝ์šฐ๊ฐ€ ๊ทนํžˆ ๋“œ๋ฌผ๋‹ค. ํ•œ์ •๋œ ํ™˜์ž์ˆ˜๋กœ ์ธํ•ด ์ž„์ƒ ์—ฐ๊ตฌ๊ฐ€ ์ง„ํ–‰๋˜๊ธฐ ํž˜๋“ค๋ฉฐ ์ง€๊ธˆ๊นŒ์ง€ ์†Œ์ˆ˜์˜ ํ™˜์ž๋ฅผ ๋Œ€์ƒ์œผ๋กœ ํ•œ ํ›„ํ–ฅ์  ์—ฐ๊ตฌ๊ฐ€ ๋Œ€๋ถ€๋ถ„์ด๋‹ค. 5๋…„ ์ƒ์กด์œจ์€ 0%โ€“37%์ด๋ฉฐ, ์„ ํƒ๋œ ํ™˜์ž๊ตฐ์—์„œ ์žฅ๊ธฐ ์ƒ์กด์ž๊ฐ€ ๊ด€์ฐฐ๋˜๊ธฐ๋„ ํ•œ๋‹ค. 1๊ฐœ์˜ ๊ฐ„์ „์ด(solitary metastatic nodule)๊ฐ€ ๊ฐ€์žฅ ํ”ํžˆ ์–ธ๊ธ‰๋˜๋Š” ์˜ˆํ›„ ์ธ์ž์ด๋ฉฐ ์ˆ˜์ˆ  ํ›„ ๊ฐ„๋‚ด ํ˜น์€ ๊ฐ„์™ธ ์žฌ๋ฐœ์ด ํ”ํžˆ ๋‚˜ํƒ€๋‚˜๊ธฐ ๋•Œ๋ฌธ์— ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์ด ํ•„์ˆ˜์ ์ด๋‹ค[28-30].

๊ฒฐ ๋ก 

์ง€๊ธˆ๊นŒ์ง€์˜ ๋ฌธํ—Œ ๊ณ ์ฐฐ์„ ์ •๋ฆฌํ•ด ๋ณด๋ฉด, ์ฆ์ƒ์„ ๋™๋ฐ˜ํ•˜์ง€ ์•Š์€ M1 ์œ„์•”์˜ 1์ฐจ ์น˜๋ฃŒ๋Š” ํ•ญ์•”ํ™”ํ•™์š”๋ฒ•์ด๋ฉฐ ํ–ฅํ›„ ๋ฐœํ‘œ๋  REGATTA ์—ฐ๊ตฌ์˜ ๊ฒฐ๊ณผ์— ๋”ฐ๋ผ reduction surgery๋ฅผ ๊ณ ๋ คํ•ด ๋ณผ ์ˆ˜ ์žˆ๋‹ค. ์ผ์ฐจ์ ์œผ๋กœ ์›๊ฒฉ ์ „์ด ๋ณ‘์†Œ์˜ ์œ„์น˜๊ฐ€ ํ•œ ๊ณณ์— ๊ตญํ•œ๋˜์—ˆ์„ ๋•Œ, ์›๊ฒฉ ์ „์ด ๋ณ‘์†Œ์˜ ๊ด€ํ•ด๊ฐ€ ๋‚˜ํƒ€๋‚œ ๊ฒฝ์šฐ conversion surgery๋ฅผ ์‹œํ–‰ํ•  ์ˆ˜ ์žˆ์œผ๋ฉฐ, ๋Œ€๋™๋งฅ ๋ฆผํ”„์ ˆ 16a2/b1์—์„œ ๊ด€ํ•ด๊ฐ€ ๋‚˜ํƒ€๋‚œ ๊ฒฝ์šฐ D2๋ฆผํ”„์ ˆ ๋ฐ ๋Œ€๋™๋งฅ ๋ฆผํ”„์ ˆ ์ ˆ์ œ๋ฅผ ํฌํ•จํ•œ ์œ„์ ˆ์ œ๋ฅผ ์‹œํ–‰ํ•  ์ˆ˜ ์žˆ๋‹ค. ๋˜ํ•œ 1๊ฐœ์˜ ๊ฐ„์ „์ด๋ฅผ ๋™๋ฐ˜ํ•œ ์œ„์•”์˜ ๊ฒฝ์šฐ, ๊ฐ„์ ˆ์ œ๋ฅผ ๋™๋ฐ˜ํ•œ ์œ„์ ˆ์ œ๋ฅผ ์‹œํ–‰ํ•  ์ˆ˜ ์žˆ๋‹ค(Fig. 2). M1 ์œ„์•”์—์„œ์˜ ์ˆ˜์ˆ ์˜ ์—ญํ• ์€ ๋Œ€๋ถ€๋ถ„ ์†Œ๊ทœ๋ชจ์˜ ํ™˜์ž๋ฅผ ๋Œ€์ƒ์œผ๋กœ ํ•œ ํ›„ํ–ฅ์  ์—ฐ๊ตฌ๋กœ ๋ณด๊ณ ๋˜๊ณ  ์žˆ๋‹ค. ๋”ฐ๋ผ์„œ ํ–ฅํ›„ ๊ฐ ์ฃผ์ œ๋ณ„๋กœ REGATTA ์—ฐ๊ตฌ์™€ ๊ฐ™์€ ๋Œ€๊ทœ๋ชจ์˜ ๋‹ค๊ธฐ๊ด€ ๊ณต๋™ ์—ฐ๊ตฌ๊ฐ€ ํ•„์ˆ˜์ ์ด๋ผ ์ƒ๊ฐ๋œ๋‹ค.

Notes

No potential conflict of interest relevant to this article was reported.

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Fig.ย 1.
Summary of REductive Gastrectomy for Advanced Tumor in Three Asian countries (REGATTA) trial (JCOG0705/KGCA01).
EP, endpoint; H1, hepatic metastasis; P1, peritoneal metastasis; LN, lymph node; LND, lymph node dissection; R, randomization.
kjco-11-1-1f1.tif
Fig.ย 2.
The role of surgery in stage IV gastric cancer. Sx, symptom; REGATTA, REductive Gastrectomy for Advanced Tumor in Three Asian countries; P+, peritoneal metastasis; H+, hepatic metastasis; PAN, para-aortic lymph node.
kjco-11-1-1f2.tif
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