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[Á¦5Â÷ »ï¼º¼­¿ïº´¿ø ½Äµµ¾Ï ½ÉÆ÷Áö¾ö] - ðû

ÀϽÃ: 2016³â 10¿ù 15ÀÏ (Åä)

Àå¼Ò: »ï¼º¼­¿ïº´¿ø ¾Ïº´¿ø ÁöÇÏ2Ãþ Áß°­´ç


1. Neoadjuvant chemotherapy for locally advanced esophageal cancer: the Japanese strategy and its rationale - Harushi Udagawa (Toranomon Hospital, Tokyo)

¿¬ÀÚ´Â ÀϺ»ÀÇ °¥¶óÆÄ°í½º Çö»óÀ» ¾ð±ÞÇÏ¿´½À´Ï´Ù. ´Ù¸¥ ¸ðµç ³ª¶ó¿Í ÀϺ»ÀÌ ´Ù¸£´Ù´Â °ÍÀÔ´Ï´Ù. ½½¶óÀ̵åÀÇ Á¦¸ñÀÌ "Why is Japanese treatment strategy of esophageal cancer different from rest of the world?"¿´½À´Ï´Ù.

1) ChemoRT vs chemotherapy

¼­¾ç¿¡¼­´Â neoadjuvant chemoRT °¡ neoadjuvant chemotherapyº¸´Ù ¿ì¿ùÇÏ´Ù°í º¸´Â °ÍÀÌ ÀϹÝÀûÀÔ´Ï´Ù. ±×·¯³ª ÀϺ»¿¡¼­´Â neoadjuvant chemotherapy aloneÀÌ »ç¿ëµË´Ï´Ù. ¿¬ÀÚ´Â ±×¿¡ ´ëÇÑ ¿ª»çÀû ¹è°æ°ú µ¥ÀÌŸ¸¦ ¼³¸íÇÏ¿´½À´Ï´Ù. ÇѸ¶µð·Î "¼ö¼ú ¹üÀ§°¡ ³ÐÀ¸¸é neoadjuvant chemotherapy aloneÀÌ ÃæºÐÇÏ´Ù. ¼­¾çÀº ÀÛÀº ¼ö¼úÀ» Çϱ⠶§¹®¿¡ neoadjuvant chemoRT°¡ ÇÊ¿äÇÏ´Ù"´Â ¼³¸íÀÔ´Ï´Ù.

"Long before the introduction of TFD (three-field lymph node dissection), Japanese surgeons first applied preoperative radiotherapy to advanced esophageal cancer in the pursuit of better survival. It was related to late diagnosis of the disease in general at that time. This strategy was denied by JCOG8201. Since then, we have concentrated our interest in postoperative chemotherapy. As a backgroud, adjuvant chemotherapy was easier to adopt in the treatment strategy including extended lymphadenectomy. JCOG9204 showed better disease free survival in 'surgery + adjuvant chemotherapy' group over 'surgery alone' group. As the concept of 'neoadjuvant threatment' was introduced and became popular, and as the safety of TFD was improved on the other hand, neoadjuvant chemotherapy became our next target. JCOG9907 clearly showed that 'neoadjuvant chemotherapy + surgery' realized better survival than 'surgery + adjuvant chemotherapy'."

2) ¼ö¼úÀÇ ¹üÀ§

Two field lymph node dissection¿¡¼­ Three-field lymph node dissection (TFD)À¸·Î ¼ö¼ú ¹üÀ§°¡ ³Ð¾îÁ³½À´Ï´Ù. Áï upper mediastinal lymph nodes¿Í cervical lymph nodes±îÁö ±¤¹üÀ§ÇÏ°Ô dissection ÇÏ´Â °ÍÀ¸·Î, ÇöÀúÇÑ »ýÁ¸±â°£ÀÇ Çâ»óÀÌ ÀÖ¾ú½À´Ï´Ù. ÀϺ»¿¡¼­ ±¤¹üÀ§ÇÑ lymph node dissectionÀÇ ¸ñÀû(ÀϺ»¿¡¼­ three-field lymph node sissection ¼ö¼ú¿¡¼­ ÀýÁ¦µÈ ¸²ÇÁÀýÀº 100°³ ÀÌ»ó)À» ´ç¿¬È÷ therapeuticÀ¸·Î º¸´Âµ¥ ¹ÝÇÏ¿©, ¼­¾ç»ç¶÷µéÀº À̸¦ ÀÌÇØÇÏÁö ¸øÇÏ°í ÀÖ´Â ½ÇÁ¤ÀÔ´Ï´Ù.

¸µÅ©

Udagawa ¼±»ý´ÔÀº "We should find out the way to survive, ourselves!"¶ó´Â ÀλóÀûÀÎ ¹®±¸·Î °­ÀǸ¦ ¸¶ÃƽÀ´Ï´Ù.

* ¼­¿ï´ëÇб³ Á¶¼®±â ¼±»ý´Ô comment: (1) Extensive surgery ÈÄ¿¡´Â ȸº¹ÀÌ ´Ê±â ¸¶·ÃÀ̹ǷΠȯÀÚ ¸¸Á·µµ°¡ ¶³¾îÁú ¼ö ÀÖ½À´Ï´Ù. ´ëÇѹα¹ Á¤ºÎ¿¡¼­´Â hospital length¸¦ ÁÙÀÌ·Á´Â ³ë·ÂÀ» ÇÏ°í ÀÖ½À´Ï´Ù. (2) ¼­¿ï´ëÇб³¿¡¼­µµ chemoRTÀÇ Ãʱ⠼ºÀûÀÌ ÁÁÁö ¾Ê¾Ò½À´Ï´Ù. ÀÌÈÄ °æÇèÀÌ ½×À̸鼭 ¼ºÀûÀÌ ÁÁ¾ÆÁ³½À´Ï´Ù. ÀϺ»°ú ¼­¾çÀÇ Á¢±Ù¹ýÀ» ºñ±³ÇÒ ¶§ ÀÌ·¯ÇÑ Á¡ÀÌ °í·ÁµÇ¾î¾ß ÇÒ °Í °°½À´Ï´Ù.

* Christopher Hayden Crane ¼±»ý´Ô (Memorial Sloan Kettering Cancer Cancer)comment: ¼­¾çÀÇ Àӻ󿬱¸¿¡¼­ surgical specimenÀÇ margin positive rate 40%, local recurrence 30%ÀÔ´Ï´Ù. ÀϺ»Àº ¾î¶²°¡¿ä?

→ Udagawa ¼±»ý´Ô ´äº¯: ÀϺ»¿¡¼­ margin positive rate´Â 5%ÀÔ´Ï´Ù. Radial margin positive´Â preoperative diagnosis°¡ À߸øµÈ °ÍÀÌÁö¿ä.


2. Indication of neoadjuvant treatment (¼­¿ï¾Æ»êº´¿ø Á¾¾ç³»°ú ¹Ú¼÷·Ã)

½Äµµ¾ÏÀº ¿©ÀüÈ÷ Ä¡¸íÀûÀÎ Áúº´ÀÔ´Ï´Ù. 2011³â ¿ì¸®³ª¶ó ÀÚ·á¿¡ ÀÇÇÏ¸é »õ·Î ¹ß»ýÇÑ È¯ÀÚ ´ëºñ »ç¸ÁÀÚ ºñÀ²Àº 67%ÀÔ´Ï´Ù.

Neoadjuvant chemoRTÀÇ È¿°ú: º¸´Ù advanced stage ȯÀÚ¸¦ ´ë»óÀ¸·Î ÇÑ CROSS ¿¬±¸´Â neoadjuvant stage¿¡ ´ëÇÑ positive result¸¦ º¸¿´½À´Ï´Ù (van Hagen P. NEJM 2012). »ó´ëÀûÀ¸·Î less advanced stage ȯÀÚ¸¦ ´ë»óÀ¸·Î ÇÑ FFCD 9901 ¿¬±¸ (Mariette. JCO 2014)´Â negative result¸¦ º¸¿´½À´Ï´Ù.

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NCCN guideline 2016¿¡´Â cT1bN+M0 ¶Ç´Â cT2-T4aN0N+M0¿¡¼­ preoperative chemoRT¸¦ ±ÇÇÏ°í ÀÖ½À´Ï´Ù. Áï submucosal cancer¿¡¼­ LN¾ç¼ºÀÎ °æ¿ì¿Í LN¿Í ¹«°üÇÏ°Ô ½É´Þµµ°¡ proper muscle ÀÌ»óÀÎ °æ¿ì´Â preoperative chemoRT¸¦ ±ÇÇÑ´Ù´Â °ÍÀÔ´Ï´Ù.

±×·¯³ª cT2N0M0¿¡ ´ëÇÑ Ä¡·á ¹æħÀº NCCN guideline°ú ´Ù¸£°Ô Á¢±ÙµÇ´Â °æ¿ì°¡ ¸¹½À´Ï´Ù. cT2N0M0ÀÇ clinical stagingÀÌ ±×¸® Á¤È®ÇÏÁö ¾Ê´Ù´Â Á¡µµ ¹®Á¦ÀÔ´Ï´Ù. Understaging µÈ ȯÀÚ¸¦ Àß °í¸¦ ¼ö ÀÖ¾î¾ß ÁÁÀº °á°ú¸¦ ³¾ ¼ö ÀÖ½À´Ï´Ù.

While some sudies have advocated for the use of preoperative therapy due to a high incidence of nodal dieases detected after resection (Zhang JQ. Ann Thorac Surg 2012), other studies have questioned whether preoperative therapy improves survival (Speicher PJ. J Thorac Oncol 2014). cT2N0M0ÀÇ preoperative chemoRTÀÇ toxicity¸¦ °í·ÁÇÒ ¶§, cT2N0M0´Â preoperative chemoRT ¾øÀÌ ¹Ù·Î ¼ö¼úÀ» ½ÃÇàÇÒ ¼ö ÀÖ´Ù°í »ý°¢µË´Ï´Ù.

GE junction cancer¸¦ ½Äµµ¾Ïó·³ Ä¡·áÇÒ °ÍÀΰ¡, À§¾Ïó·³ Ä¡·áÇÒ °ÍÀÎÁö ³í¶õÀÔ´Ï´Ù. µ¿¼­¾çÀÇ Á¶Á÷Çü Â÷ÀÌ°¡ Å®´Ï´Ù.


3. Pre-treatment and post-treatment staging of esophageal cancer (»ï¼º¼­¿ïº´¿ø ¿µ»óÀÇÇÐÈ­ ±èÅÂÁ¤)

Æó¾ÏÀº ³»³âºÎÅÍ 8ÆÇÀÌ »ç¿ëµÉ ¿¹Á¤Àε¥ ½Äµµ¾ÏÀº ¾ðÁ¦ 8ÆÇÀÌ ³ª¿ÃÁö ¸ð¸¨´Ï´Ù. µû¶ó¼­ ½Äµµ¾Ï¿¡¼­´Â ´çºÐ°£ 7ÆÇÀÌ »ç¿ëµÉ °ÍÀÔ´Ï´Ù. 7ÆÇÀÇ Æ¯Â¡Àº histologic gradingÀÌ T staging¿¡ ¿µÇâÀ» Áشٴ Á¡ÀÔ´Ï´Ù. N staging´Â °¹¼ö·Î ´Ü¼øÇØÁ³´Âµ¥, 1-2°³¸é N1, 3-4°³´Â N2ÀÔ´Ï´Ù.


4. Esophagectomy after neoadjuvant chemoRT (¼­¿ï¾Æ»êº´¿ø ÈäºÎ¿Ü°ú ±è¿ëÈñ)

¾Æ»êº´¿ø¿¡¼­´Â cT1-2N0´Â ¼ö¼ú, cT3/4N+´Â neoadjuvant chemoRTÀ» ÇÏ°í ÀÖ½À´Ï´Ù.

CCRT¿¡ ¹ÝÀÀÀÌ ÁÁÀ¸¸é ¼ö¼úÀ» ´õÇÏÁö ¾Ê°í CCRT¸¦ °è¼ÓÇÏ´Â °ÍÀÌ ÁÁ´Ù´Â ¿¬±¸°¡ ÀÖ½À´Ï´Ù¸¸, ¾Æ»êº´¿øÀÇ ÀÚ·á¿¡ ÀÇÇϸé CCRT ÈÄ ¼ö¼úÇÑ È¯ÀÚ°¡ CCRT ´Üµ¶º¸´Ù survivalÀÌ ÁÁ¾Ò½À´Ï´Ù.

Time interval of esophagectomy/CCRT: The operation is usually performed 4 to 8 weeks after CCRT when the patient has fully recoverd. Longer waiting may increase the rate of pathologic complete reponses and may improve survival.

ÀÌÁØÇà Áú¹®. Clinically T2N0 ·Î Æò°¡µÇ¾î initially surgery¸¦ Çß´ø ȯÀÚÀÇ postop lymph node stagingÀº ¾î¶°ÇÏ¿´´ÂÁö¿ä?


5. Neoadjuvant therapy followed by surgery in locally advanced resectable esophageal cancer (»ï¼º¼­¿ïº´¿ø ¿Àµ¿·Ä)

CROSS trialÀÇ longterm data°¡ 2015³â ¹ßÇ¥µÇ¾ú´Âµ¥ °ú°Å ÀڷḦ È®ÀÎÇÏ´Â ¼öÁØÀ̾ú½À´Ï´Ù (Shapiro. Lancet oncology 2015).

¾Æ·¡´Â neoadjuvant chemoRT ¹ÞÀº »ï¼º¼­¿ïº´¿ø ȯÀÚÀÇ ÃÖ±Ù °á°úÀÔ´Ï´Ù (Cho WK. Oncotarget 2016). ´ç¿¬ÇÑ À̾߱â°ÚÁö¸¸ ¼ö¼ú¹ÞÀº ȯÀÚÀÇ »ýÁ¸À²ÀÌ ´õ ÁÁ¾Ò½À´Ï´Ù. ¹°·Ð ¼ö¼ú¹ÞÁö ¾ÊÀº ȯÀÚ¿¡¼­µµ ÀÏÁ¤ ºÎºÐ longterm survival ¿¹°¡ ÀÖ½À´Ï´Ù.

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¾ÆÁ÷±îÁö´Â neoadjuvant chemotherapy ÈÄ CRÀÌ ¿Ô´õ¶óµµ ¼ö¼úÀ» ÇÏ´Â °ÍÀÌ Ç¥ÁØÀ̶ó°í »ý°¢µË´Ï´Ù.


5. PD-1/PD-L1 inhibitor therapy for locally advanced esophageal cancer. (»ï¼º¼­¿ïº´¿ø Ç÷¾×Á¾¾ç³»°ú ¼±Á¾¹«. 2000³â ¼­¿ïÀÇ´ë Á¹¾÷)

Pembrolizumab (PD-1 inhibitor) »ç¿ë ÈÄ ÇöÀúÈ÷ È£ÀüµÈ Æó¾Ï (adenocarcinoma) Áõ·Ê¸¦ º¸¿©ÁÖ¾ú½À´Ï´Ù. ¸Å¿ì Á¶¿ëÇÑ Ä¡·á¶ó°í Çϼ̽À´Ï´Ù. ºÎÀÛ¿ëÀÌ °ÅÀÇ ¾ø±â ¶§¹®ÀÔ´Ï´Ù.

Melanoma¿¡¼­ PD-L1 immunohistochemistry ¾ç¼ºÀ̸é response rate°¡ 67%ÀÎ ¹Ý¸é À½¼º¿¡¼­µµ response rate°¡ 19%À̹ǷΠ°ú¿¬ À̸¦ predictive marker¶ó°í ÇÒ ¼ö ÀÖÀ»Áö ¾ÆÁ÷ ³í¶õÀÔ´Ï´Ù.


7. Neoadjuvant CCRT for locally advanced esophageal cancer. Christopher Haydon Crane (Memorial SLoan Kettering Cancer Center)

ChemoRT´Â margin negative resection rate¸¦ ¿Ã¸³´Ï´Ù.

º´¼Ò À§Ä¡¿¡ µû¶ó margin positive rate¿¡ Â÷ÀÌ°¡ ÀÖ½À´Ï´Ù. »óºÎ½Äµµ¿¡¼­´Â margin positive rate°¡ ³ô½À´Ï´Ù.

Cardiopulmonary complicationÀ» ÁÙÀ̱â À§ÇÏ¿© dose delivery°¡ ÁÁ¾Æ¾ß ÇÕ´Ï´Ù.

* Udagawa ¼±»ý´Ô Áú¹®¿¡ ´ëÇÑ ¿¬ÀÚÀÇ ´äº¯: ¹Ì±¹ÀÇ R0 resection rate°¡ ³·Àº ÀÌÀ¯¿¡ ´ëÇÏ¿© ¿¬ÀÚ´Â (1) ¹Ì±¹¿¡´Â Çѱ¹, ÀϺ», Áß±¹°ú °°Àº high volume center°¡ ¾ø´Ù´Â Á¡, (2) ¹Ì±¹ ȯÀÚµéÀº obesity°¡ ¸¹´Ù´Â Á¡À» µé¾ú½À´Ï´Ù. → ÀÌ¿¡ ´ëÇÏ¿© ÁÂÀå ¾È¿ëÂù ¼±»ý´ÔÀº (3) ÀϺ» surgeonÀÌ ¸Å¿ì aggressiveÇÏ´Ù´Â Á¡ÀÌ Å« Â÷À̸¦ ¸¸µç´Ù°í comment ÇÏ¿´½À´Ï´Ù.

* FloorÀÇ ÇÑ ¼±»ý´Ô comment: CROSS trialÀº ȯÀÚ°¡ Àþ°í °Ç°­ÇÑ ÆíÀ̾ú½À´Ï´Ù. ¿ì¸® ȯÀÚµé°ú »ó´çÈ÷ ´Ù¸¨´Ï´Ù.


8. Esophageal cancer in Korea

¿ì¸®³ª¶ó¿¡¼­ ½Äµµ¾ÏÀº ¸ðµç ¾ÏÀÇ 1% Á¤µµ¸¦ Â÷ÁöÇÏ°í ÀÖ½À´Ï´Ù. ¸Å³â 1,400¸íÀÌ ½Äµµ¾ÏÀ¸·Î »ç¸ÁÇÕ´Ï´Ù. ½Äµµ¾Ï ¼ö¼ú¿¹´Â 2014³âÀÇ °æ¿ì Àü±¹ÀûÀ¸·Î 414¸íÀ̾ú½À´Ï´Ù (ÀÌ Áß 62.8%ÀÎ 260¸íÀÌ »ï¼º¼­¿ïº´¿ø¿¡¼­ ¼ö¼úÀ» ¹Þ¾ÒÀ½).

1994³âºÎÅÍ 2014³â±îÁö »ï¼º¼­¿ïº´¿ø¿¡¼­ ½Äµµ¾Ï ¼ö¼úÀº 1,538¿¹°¡ ÀÖ¾ú½À´Ï´Ù. Mean age´Â 63.3¼¼, ³²ÀÚ 93%, 2-FLND 85% & 3-FLND 10%, Median hospital stay 12ÀÏ, 30 day mortality 0.8%¿´½À´Ï´Ù. Squamous cell carcinoma, primary surgery, R0 resectionÀÇ °æ¿ì 5³â »ýÁ¸À²Àº 64.7%¿´½À´Ï´Ù (1±â 82.7%, 2±â 63.5%, 3±â 41.2%, 4±â 46.9%).


[References]

1) EndoTODAY ½Äµµ¾ÏÀÇ Ä¡·á

2) 2014³â »ï¼º¼­¿ïº´¿ø ½Äµµ¾Ï ½ÉÆ÷Áö¾ö

© ÀÏ¿ø³»½Ã°æ±³½Ç ¹Ù¸¥³»½Ã°æ¿¬±¸¼Ò ÀÌÁØÇà. EndoTODAY Endoscopy Learning Center. Lee Jun Haeng.