TCNCYH Phu truong 80 (3D) - 2012
Dl£U TR! UNG THU' DAI TRANG GIAI DOAN III BANG HOA C H A T B6 TRO SAU P H A U THUAT
N g u y l n Thi T h u H u ' d n g \ L6 VSn Q u a n g \ N g u y l n T u y l t M a l ^ Hoang Manh T h l n g ^ 'Truryng D$i hpc Y Hd Ndi; 'Khoa Ndi B$nh vi$n K Hd N(ii
Nghiin cuv duxyc thuc hi$n nhim dinh gid kit qui diiu tri phin IhuH kit hep hoi chit ung thu- dai tring giai doan III Kit qui cho thiy ty 10 s6ng thim toin bd (OS) 69,4%, sSng thdm khdng binh (DFS) 5 nim 50.0% Sdng mm toin bd 5 nim giai doan III a. b, c tu^ng tmg Ii 85,7%. 75,8%. 40.6% (p < 0,05) S6ng Ihdm 5 nSm giai doan llla.b.c tuvng ung 72.9%. 50,9%. 32,7% (p < 0.01) S6 luvng hach di cin. ndng dd CEA tni-dc m6, Ihi md b^nh hpc Ii nhung yiu t6 bin luvng cd gii tq Idi kit qui diiu In Oiiu trj hda chit bd lr<y phic dd F0LF0X4 cho ly h OS •^i DFS 5 nim cao hon phic d6 FUFA (85,6% so vdi 62,5%, 55,9% so vdi 47.4%) Kit qui nghidn cuv cho phip rut ra mdt s6 kit luin Ii s6 liiung hach di cSn. ndng dd CEA tnj-dc md, thi md binh hqc. phic dd lids chit hd trw Ii nhOng yiu td Ii6n quan din kit qui sdng thim
Tu kh6a Ung thu d^l t r i n g . giai do^n III, hda c h i t b l trg- sau p h i u thu^t
I. DAT VAN
B £Tai Viet Nam. ung t h u dai trdng (UTDT) d&ng thu 4 v l ty te m l c d ca 2 gidi Nguy c o t u vong cua bdnh lien quan tryc tiep tdi cac y l u td nguy c o dl can, trong dd bach h u y l t id con dudng di can chu y l u vdi ty id 37% Di can hach ludn la mdt yeu to tien luong x l u anh hudng k i t qua d i l u trj
Mac du UTDT da dl can hach nhung n h i l u truong hpp d i l u tn v i n cho k i t qua kha quan P h i u thuat la phuong phap d i l u tn can ban trong dd vai trd vet hach la h i t sue quan trpng Hda chat bo tro n h l m tieu didt nh&ng d di can vi the vd lam giam cac y l u to nguy c o tai phat, d u o c ch&ng minh lam tang thdi gian s i n g Nhieu phdc dd hda c h i t dang dup'c ap dyng nhung v i n de la phae do nao mang lai hidu qua toi u u n h i t v i n dang dupe nghien cuu, R i t n h i l u nghien c u u idn tren the gidi da ch&ng minh vai trd hda c h i t bo trp' vdi UTDT di can hach Trong khi dd tai Vidt Nam chua cd nghidn cuu ndo danh gia cac dac d i l m , k i t qua d i l u tn va lam n i l bat dup'c vai trd cua hda c h i t k i t hp'p phau thuat tren mpt nhdm d i i tup'ng neng biet dd la UTDT dl can hach, Myc tieu cua nghien c&u ndy n h l m danh gia k i t qua d i l u tn b l n g hda c h i t sau p h i u thuat UTDT giai doan III va mdt so y l u t l anh hudng k i t qua d i l u tn
II. D 6 | TU'ONG VA PHU'ONG PHAP
1 . D d i t y o n g
Benh nhan dup'c l u a chpn phai dup'c p h i u
thuat tridt can va md bdnh hpc sau md khing d|nh ung t h u b i l u m d dai trang di can hach (giai doan III) T h i trang loan than trong gidi han cho phep (chl s6 toan trang t u 0 den 1) Bdnh nhan cd b l n g ch&ng di can xa, t i l n s u m l c benh man tinh, tim mach nang, suy than, bat t h u d n g v l tinh than bl loai khdl nghien c u u Sau p h i u thuat tndt can, bdnh nhan phai dup'c dieu tn hoa c h i t t)d trp- trong 6 thang vdi mdt trong 2 phac d d FUFA (MayoClinc 5-FU/Leucovonne) hoac F0LF0X4 (Oxaliplatin + FU/Leucovonne)
2. T h i l t k l n g h i e n c & u ; nghien c&u hdi cuu trdn 90 b$nh nhan ung t h u b i l u m d dai trdng giai dogn III tai bdnh vi$n K t& 2005 d i n 2010.
3. P h a n t i c h s d i i e u
Oanh gia k i t qua d i l u tn d y a vao thdi gian song toan bd, thdi gian sdng khdng b i n h .
Thdi gian s i n g toan bd (OS) dup'c xac dinh la khcang thdi gian sau p h i u thuat tndt can tdi ngay banh nhan c h i t do bat c& nguydn nhan gi. Thdi gian sdng khdng bdnh (DFS) d u o c xdc dinh la khoang thdi gian t u sau p h i u thuat tridt can d i n thdi d i l m tai phat hoac di can (theo tidu chuin RECIST) Danh gia k i t qua d i l u tri theo mdt so y l u nhu: t u i i , gidi, tinh trang thieu mau, vi tri va kich thudc u, ndng dd CEA trude p h i u thuat, m&c dd u xdm l l n thanh dai trang, m&c d d di can hach, t h i md benh hpc, phac d d dieu tri hda c h i t . Sd lidu
TCNCYH Phu truong 80 (3D) - 2012
d u o c x u ly b l n g p h i n mem SPSS 16 0, ddnh gia thdi gian sdng va thdi gian tai phat di can b l n g phuong trlnh Kaplan - Meier vdi k i l m djnh
III. K£T QUA
Log-rank, So sanh, k i l m d|nh s y khac biet gi&a cac b i l n dinh tinh gi&a 2 nhdm b l n g test x^. cac so sanh c6 y nghTa thong kd khi p < 0,05,
1. T h d i gian s d n g toan b d va k h d n g benh
B a n g 1 . T h d i g i a n s d n g t o a n bp va k h d n g b e n h t h e o t i r n g n a m
1 nam 2 nam 3 n§m 4 nam 5 nam
Sd benh nhdn T P - D C
10 23 23 24 26
Sd benh nhan khdng TP- DC
80 67 67 66 64
Sd b^nh nhan c d n s i n g
85 74 71 71 71
DFS % 87,1 66,4 66,4 64,0 50.0
0 S % 93,4 76.0 69,4 69,4 69,4 Thdi gian song trung binh 5 nam:'55,8 ± 3.2,
Survival Function
V
Survival Functioi
B i e u d o 1 . T h d i g i a n s d n g t o a n b d u n g tnlp B i l u d d 2. T h d i g i a n s d n g k h d n g b e n h dai t r a n g g i a i d o a n III ung t h u ' d a i t r a n g g i a i d o a n III Ty le t u vong xay ra chu y l u trong 3 nam d i u . sau 1 nam ty id song (a 93,4%, sau 2 nam la 76,0%, sau 3, 4, 5 nam la 69,4%, ty le song toan bd va song khdng benh 5 nam tuong &ng la 69,4%, thdi-gian s i n g trung binh 55,8 thang
2. Lien quan k i t qua d i l u trj v d i mpt s d y l u t d
Ndng dp CEA trude md, muc dp u xam l l n da day, m&c dd di can hach, giai doan b^nh va t h i md benh hoc la y l u td tidn lupng cd y nghTa anh hudng d i n k i t qua ngudi benh vdi (p < 0,05). Thdi gian song toan bd va sdng khdng bdnh d nhdm benh nhan dieu tri F 0 L F 0 X 4 cao hon FUFA, tuy nhien s y khac bidt chua cd y nghTa t h i n g ke.
TCNCYH Phu truvng 80 (3D) - 2012
B d n g 2. Ode d i i m b $ n h n h d n vi s y l i i n q u a n k i t q u d d i i u t r i v d i m d t s i y i u t d
T u i i
S i b i n h nhSn (%) DFS 5 nSm (%) OS 5 n j m (%) Nam
NO
48(53,3)
p = 0,66
58,1
42(46,7)
16(17.8) 74 (82,2)
45,2 p = 0.554
39,2 69,2
83.5 p = 0.017
53.6 736
p = 0,39Khdng
OTT OT Sigma
54 (60) 36 (40)
41 (45,6) 5 (6,7) 20 (22,2) 22 (24,5)
50,7 56,4 p = 0,25
43,3
p = 0,538
78,4 56.8 p = 0.16
71
p = 0.878 23(25,e
67 (74.4)
38.6 52,5 p = 0.423
73,7 p > 0 . 0 5
CEA t r y d c mo
<10 ng/ml 110 ng/ml
64(71,1) 26(18,9)
60.5 32.8
75.8 54.4 p = 0.049 T2
T3-4
8 (8.9)
82(91,1) 49,1
p = 0,89
85,7 67,7 p = 0.0457 N1
N2
70 (77,8) 20 (22,2)
51.1
p = 0,000
76,9
8 (8.9) 62 (66,9)
20 (22,2) 32,7
p = 0.002
85.7
p = 0.024
TCNCYH Phu truong 80 (3D) - 2012
Sd b?nh nhan (%) DFS 5 nam (%) OS 5 nSm (%)
Md benh hoc
UTBMT BH thip UTBMT BH vira UTBMT BH cao UTBMT nhdy
3 (3,3) 55(61,1) 14(15.6) 17(18,9)
50,0 56,5 76,4 0
50,0 73 73.3 69,1
Khdng BH 1(1,1)
Phac d d hoa chat
44 (48,9)
46(51,1) 85.9
IV. BAN LUAN
P h i u thuat la phuong phap d i l u tn co ban vdi UTDT dl can hach, hda c h i t bo trp' n h l m tidu diet not nhung t l bdo ung thu cdn sdt lai vd giam nguy CO tai phat Nghien c&u NSABP C-07 cho ty Id OS 4 nam d nhdm bdnh nhan giai doan 111 p h i u thuat tnet can la 71,8%, nghien cuu MOSAIC (a t u 76%
d i n 78,5% tuy vao phac do hda c h i t bo tro [3]
T r i n T h i n g (2010) cho t h i y OS d nhdm d i l u tn bd tro vdi FUFA Id 65,9% [1]. Trong nghien c&u cua Chung tdi, ty Id ndy la 69,4%, thdi gian sdng trung binh 55.8 ± 3,2 thdng Hda c h i t bo trp dd lam tang dang ke thdi gian sdng cho benh nhan. Khi so sanh vdi mdt sd nghien c&u trude ddy tai Viet Nam tren ddi tuong p h i u thudt don t h u i n hoac khdng phai tat ca d u o c d i l u tn hda chat bo tro ty id OS 5 nam r I t thap chf t& 33.3% d i n 45,9% [2]
Tai phat di can la dac tinh cua bpnh ung thu, vdi UTDT khoang 1/2 benh nhan cd di can hach se ddi dien vdi nguy c o tai phat Dogan (2010) cho r i n g ty le tai phat c h i l m tdi 4 2 % [4J Tac gia Nguyen Dai Binh cho r i n g sau thdi d i l m 3 nam h l u h i t benh nhan on dinh it tai phat di can [2], Trong nghien cuu cua chCing tdi, tai phat di can xay ra chu y l u frong 3 nam d i u , ty le tai phat 5 nam la 28,9%, vdi ty le DFS 5 nam la 50%, trong dd nam th& 1 ed 10/90 bdnh nhan tai phat ty I? DFS la 87,1%, sau nam t h u 2 va th& 3 cd 23/90 benh nhan fai phat, ty le DFS la 66,4% Sau nam thu 4 va th& 5 ty le DFS t u o n g &ng la 64% va 50%
Mpt s d y l u t d tien lup'ng
Mu'c dd u xdm l l n thanh dai trang dupe coi la y l u to tidn luong benh Trong nghien c&u nay, ty le DFS, OS 5 nam d nhdm T1-2 cao hon T3-4, tuy nhien s u khdc bidt khdng cd-y nghTa On Suzuki (2006) cung cho k i t qua tuong t y [5] Mdt sd tdc gia cho r i n g m&c do di can hach phg thudc m&c dd u xam l l n , t u dd anh hudng tdi k i t qua d i l u trj Hach dai trang d u o c coi la hang rao bao ve dau tidn giup CO t h i chdng lai s y lan tran benh M&c dd di can hach la y l u to tien luong quan trong anh hudng k i t qua d i l u tn Nghien c&u cua Alfred trdn 306 bdnh nhdn ung thu dai trang p h i u thuat tnet can don t h u I n cho t h i y OS 5 nam giam d i n theo sd luong hach di can, OS cua nhdm 1, 2, 3, 4, 5, ^- 6 hach di can tuong &ng Id 69%, 6 1 % , 63%, 56%, 42%, 27% [6] Tang ch&ng minh r i n g ty Id OS 5 nam d nhdm N1 (£ 3 hach di can) cao hon cd y nghTa so vdi N2 (tren 3 hach di can) (67% vs 36%, tuong &ng) [7], Trong nghidn c&u nay OS 5 ndm cua N1 cao hon ed y nghTa so vdi N2 (76,9% so vdi 40,6%, p = 0.007),
OS 5 nam UTDT giai doan Ilia Id 85,7% cao hon giai doan lllb la 75,8%i. va giam g i n 1 nua d giai doan lllc vdi 40,6%, s y khac biet cd y nghTa thong ke vdi p < 0,05, Cung tuong t u , ty le DFS d Ilia la 72,9%, lllb la 50,9%, va giam h i n d giai doan lllc la 32,7%, s u khac bidt cd y nghTa thong ke vdi p = 0,02. Mac du giai doan benh d u o c danh gia dua tren 2 y l u td muc dd u xdm lan va m&c dd di can hach, song di can hach la y l u t l quan trpng n h i t anh hudng k i t qua d i l u th.
TCNCYH Phu truong 80 (3D) -2012
CEA trude m l la y l u td tidn lup'ng ed gia trj vdi ung thu b i l u md t u y i n dgi trang, DFS va OS d nhdm cd CEA d u d i lOng/ml d i u cao hon cd y nghTa so vdi nhdm trdn 10 ng/ml (DFS 60,5% so vdi 32,8%, p = 0,035, OS 75,8% so vdi 54,4%, p = 0,049) thdi gian s i n g them trung binh tuong ung la 59,5 thang so vdi 45,1 thang Theo Park (2009) DFS t h i p d nh&ng benh nhan cd n i n g dd CEA tru'dc md cao (p < 0,0001) [8] Bannura cho r i n g CEA tru'dc m l Id y l u t l tidn lup-ng ddc lap vdi ung thu b i l u md l u y i n dai tryc trdng va m&c cao cua nd gp'i y bdnh t i l n triln [9]
Logi md bdnh hpc K i t qua r I t x l u d nhdm ung thu bieu md khdng bidt hda vdi OS 5 ndm la 0%, t i t c^ d i u tai phat trong 2 nam d i u Trong nhdm ung thu b i l u md t u y I n ty le DFS vd OS cOng tang d i n theo muc dd biet hda cua t l bao, ty Id DFS tuong &ng d dd bidt hda t h i p , v&a, cao la 50,0%.
56.5%, 76,4% (p = 0,781), ty H OS tuong ung d cac dd bidt hda t h i p , vua, cao Id 70,0%, 73,0%, 73,3% (p = 0,896) Cdn ddi vdi ung thu b i l u md c h l nhay, ty Id OS 5 nam la 6 9 , 1 % thap hon so vdi ung thu b i l u md tuyen Nghidn cu'u cua Kanemitsu tren 2,678 cho t h i y OS 5 ndm vdi ung thu b i l u md C h l nhdy t h i p hon so vdi ung thu bieu md khdng c h l nhay (54,0% so vdi 73,3%, p = 0,002) [11]
Thdi gian song d nhdm tuoi d u d i 40 t h i p hon so vdi nhdm tudi tren 40 (OS 5 ndm- 38,6% vdi 51,9%, DFS 52,5% vs 73,7%, p > 0,05) Gidi nam tidn luong xau hon gidi n& (OS 5 nam 5 8 , 1 % vd 83,5%, song trung binh d nam 49,3 thang so vdi d n& la 50,7 thang, p = 0,017), Andrew da nhan d|nh tuoi va gidi anh hudng dang k l tdi ,0S trdn benh nhan UTDT cd di can, n u gidi tre t u l i (< 45tu6i) cd thdi gian song ddi hon nam gidi (17 thang so vdi 14 thang, p < 0.0001). Ngup'c lai phg n& trdn 55 tuoi cd OS x l u hon rd ret so vdi nam gidi (7 thang so vdi 9 thang, p < 0,0001) [12], Khi danh gia m l i quan hd cua tinh trang t h i l u mau vdi k i t qua d i l u tn Chung tdi khdng t h i y s y khac bidt cd y nghTa
Vai t r d cua phac d d hda c h i t b d tro' Vdi thdi gian theo ddi trung binh 33.28 thang k i t qua d i l u tri cho t h i y ca thdi gian DFS va OS d nhdm benh- nhan dieu tn F 0 L F 0 X 4 cao hon d nhdm dieu tr( 5-FU/LV (DFS - 55,9% so vdi 47,4%;
OS 85,6% so vdi 62.5%, p > 0,05).
Nghien c&u MOSAIC danh gia hieu qua cua
vide p h l i hp'p oxaliplatin vdi 5-FU/LV trong d i l u tri bd trqr UTDT so vdi 5FU/LV don t h u I n Ty le DFS 3 nam cho t h i y cao hon h I n d nhdm d i l u tn FOLFOX so vdi 5FU/LV (78,2% va 72.9%, p = 0,002) va giam dup'c 23%. nguy c o tai phat [13] NSABP C-07 tuy khdng so sanh tryc t i l p phac d l F 0 L F 0 X 4 vdi FUFA nhung cOng danh gia vai trd ciia Oxaliplatin p h l i hp'p 5FU/LV K i t q u i cho t h i y ty 11 DFS 5 nam cao hon d nhdm p h l i hop Oxaliplatin so vdi 5FU/LV d o n t h u I n (76,1%
so vdi 71.8%, p = 0,0034} Tai bfinh vien K trong vdng 2 nam g i n day. F 0 L F 0 X 4 g i n nhu thay t h i FUFA Irong d i l u In b l tre Vdi thdi gian theo ddi phac d i F 0 L F 0 X 4 trong khoang 2 nam, s6 lupng benh nhan theo dOi cdn khifim t i n cd le chua du d l danh gia hi$u qua cua nd
V. KfeT LUAN
Qua nghidn c&u chiing tdi rut ra ket luan la s i lup'ng hach di can, n i n g dd CEA trude mo, t h i md b$nh hpc, phdc dd hda c h i t bd trpr la nh&ng yeu to lidn quan d i n k i t qua sdng thdm.
TAI LIEU THAM K H A O
1. T r i n T h i n g , Pham Duy H i l n , Od H u y i n Nga va c p n g SIF (2010). Nghidn c&u ap dung hda tn lidu bd tro phac dd FUFA sau p h i u thuat ung thu b i l u md t u y I n dai trang Tap chl ung thu hpc Viet Nam, Hdi thao qudc gia phdng chdng ung thu l l n thu XV, 373-383
2. N g u y l n Dai B i n h , T d Quang Huy, Bui Di^u va c d n g s y (2010). Danh gia thdi gian sdng th6m sau d i l u tri ung t h u dai tryc trang Dukes A-B-C tai khoa ngoai Tam Hiep b$nh vidn K. Tap chi ung thu hpc Viet Nam. Hdi thao qudc gia phdng chdng ung thu l l n thu XV, 367-372.
3. L o m b a r d i L. Morelli M, Cinieri S, et al (2010). Adjuvant colon cancer chemotherapy, where we are and where we'll go, Cancer treat- ment reviews 3683 (2010), 3 4 - 4 1 .
4. Dogan L, K a r a m a n N (2010). Characteristics and nsk factors for colorectal cancer recurrence. J BUON-2010-15(1). 61-67
5. On S, Y o s h i a k i S, T u n e o S (2006). Number of lymph node metastases is better predictior of prognosis than level of lymph node metastasis in patients with node-positive colon cancer J Ameri-
TCNCYH Phu truong 80 (3D) -2012
can College of Surgeons, 732-736 10. Lindmark G, Bergstrom R, Pahlman L 6. Alfred M.C, Salvatore T, Frank C (1991). (1995). The association of preoperative serum Prognosis of node-positive colon cancer. Cancer, tumour markers with Dukes' stage and survival in 1 8 5 9 - 1 8 6 1 colorectal cancer Br J Cancer 1995 May, 71(5),
7. Tang R, Wang J, Chen J (1995). Sun/ival ''090-1094
impact of lympnode metastasis in TNM stage 111 1 1 . Kanemitsu Y, Kato T, Hirai T (2003). Sur- careinoma of the colon and rectum J Am Coll Surg vival after curative resection for mucinous adeno- 1 9 9 5 , 1 8 0 , 7 0 5 - 7 1 2 carcinoma of the colorectum, Dis Colon rectum
8. Park IJ, Choi GS, Lim KH (2009). Serum 2003 Feb, 160-7
carcinoembryonic antigen monitonng after curative - ^ « j •• r. „ ^ .- •. . , - , „ „ „ , ' 12. Andrew H, Dongyun Y, Felicitas L (2009).
resection for colorectal cancer clinical significance o ^ " ^ i » . . i i i , . , . , .__ „ „ , Gender disparities in metastatic colorectal cancer
survival Clin Cancer Res 2009, 15(20), 6391-6397 of the preoperative level Ann Surg Oncol 2009
Nov, 3087-3093
9. Bannura G., CumsNIe M.A, Contreras J et '^^- Catherine L.K, Kahn, John .., Adams al (2004). CEA as an independent pronostic factor (2010). Adjuvant chemotherapy use and adverse in colorectal carcinoma Rev Med Chil, 132(6), events among older patients with stage III colon 691-700 cancer. Jama, 1037-1045
Summary
THE OUTCOME OF STAGE III COLON CANCER TREATED WITH RADICAL SURGERY AND ADJUVANT CHEMOTHERAPY
The study was to evaluate the outcome of stage 111 colon cancer was treated With radical surgery and adjuvant chemotherapy The results showed that median survival was 55 8 months, the overall survival 5-years rate was 69 4 % and DFS 5 years rate was 50% Significant OS and DFS with stage Ilia, lllb, lllc (OS 5 years rate of stage Ilia, lllb, lllc was 85 7%, 75 8%, 40 6%, respectively, p = 0 024, DFS-5 years rate of stage Ilia. lllb. lllc was 72 9%, 50 9%, 32 7%, respectively, p = 0,002). The number of lymph node metastasis, preoperative CEA. and pathology were the significant prognostic factors depend on the treat- ment outcome. Adjuvant chemotherapy with F 0 L F 0 X 4 regimen have survival higher than FUFA regimen (OS 5 years rate: 85.6% vs 62 5%; DFS rate: 55,9% vs 47 5%, p = 0 072)
Key words: colon cancer, stage III, adjuvant chemotherapy
DAC DIEM CQN HEN P H ^ QUAN KHb"! PHAT DO RHINOVIRUS Cf TRg EM
Nguyln Thj Dieu Thuy TrifOng Dai hoc Y Ha N6i Nhiim virus dudng hd hap, nhit Ii Rhinovirus (RV) duvc coi Ii yiu to chu yeu gay khdi phat can hen cap d ca ngimi Idn vi tre em Nghien cuv du-QC tien hinh nhim xac dinh ty le-nhiem Rhinovirus trong con hen cap a tre em va danh gii mpt sd dac <Sim cua can hen dp khdi phit do Rhinovirus Nghien cuu tiin cuv md ta d tre dudi 15 tudi, trong can hen cip Kit qua nghien cuv cho thay trong 146 tre du tieu chuan tham gia nghien cuv, 72,6% tre nhiim Rhinovirus So sanh can hen cap giO-a nhdm tre cd nhiim RV vi nhdm tri khong nhiem RV cho thiy nhdm tre nhiem RV cd nguy ca mic can hen cip nang han (OR = 5,1, 95% CI: 1,69 - 15,44), tri$u chung khd khe thuxmg gap nhiiu han. Tyli ting bach cau trong miu d nhdm nhiim RV la 68,5% so vdi nhdm khdng nhiim RV Ii 45% (p < 0,05) Ty 1$
tang bach cau ii toan d nhdm cd nhiim RV Ii 34,9% so vdi 15% a nhdm khdng nhiim RV. Nhiim Rhinovirus Ii nguyen nhin thudng gap giy khdi phit can hen cap d tri em vi lim ting nguy can hen cip nang.
Tu khoa: hen phi quan, rhinovirus
