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C7L, .. ;852   '   / ( ! !, !,% $"        & #' "  Yu.A.Barsukov, S.I.Tkachev, V.I.Knysh, N.D.Oltarzhevskaya, M.A.Korovina, S.P.Yarmonenko, A.A.Vainson, A.V.Nikolaev, A.T.Gradyushko, O.A.Vlasov, A.G.Malikhov, D.V.Kuzmichev, V.M.Kulushev, D.A.Oskirko, V.A.Aliev Kombined Treatment of Rectal Cancer with Preoperative Irradiation and One or Two Radiomodificators ;NG52K5 A;>20: @0: ?@O9 :8H:8, :>20==>5 ;5G5=85, @048>48D8:0B>@K, ?>;8@048>48D8:0F8O Keywords: rectal cancer, combined treatment, radimodulators, polyradiomodification # & 8E8=0  3. >A:20 Russian Cancer Research Center, Moscow $ " &5;L: >2KA8BL MDD5:B82=>ABL ?@54>?5@0F8>==>9 ;CG52>9 B5@0?88 =0 >A=>25 8A?>;L7>20=8O =5A:>;L:8E @048>48D8:0B>@>2 2 :>20==>< ;5G5=88 @0:0 ?@O9 :8H:8. 0B5@80; 8 4K:  >A=>2C @01>BK ?>;>65= 0=0;87 @57C;LB0B>2 E8@C@38G5A:>3> 8 :>20==>3> ;5G5=8O 961 1>;L=KE, 2:;NG5==KE 2 B@8 ?@>B>:>;0 ?@>A?5:B82=KE @0=4>20==KE 8AA;54>20=89 1>;55 G54 =01;N45=8O 2 # & 8E8=0 . # 276 87 =8E ?@>2545=0 ?@54>?5@0F8>==0O ;CG520O B5@0?8O (5 @ 2 B5G5=85 5 4=59 4> ! 25 @59), C 395 2K?>;=5=> B>;L:> >?5@0B82=>5 2. @54>?5@0F8>==0O B5@;CG520O B5@0?8O (G0AB>B0 M;5:B@>;510=89 460 F ?@8 2=CB@8@5:B0;L=>3@520=88) ?@>2545=0 C 224 1>;L=KE. @>3@0<A?>;L7>20=85A5=A818;870B>@>2 (;>:0;L=>9 !'-38?5@B@5@=>0:F5?B>@=>3> A>548=5=8O =8407>;0, 22>483> 2=CB@8@5:B0;L=>) ?@>2545=0 C 66 ?0F85=B>2 (?0B5=B >AA89A:>9 $545@0F88 ! 2234318 >B 2004 3.). 57C;LB0BK: OB8;5B=85 @57C;LB0BK :>20==>3> 40 ;5G5=8O A 8A?>;L7>20=854=>9 ?@54>?5@0F8>==>9 ;CG52>9 B5@0?88 C;CGH5=K (=0 13.9%) 70 AG5B A=865=8O G0AB>BK ;>:>@538>=0@=KE @5F8482>2 @0:0 (A 19,8% 2 E8@C@38G5A:>9 3@C??5 4> 8,7% ?@8 :>20==>< ;5G5=88). @8 ?@8?5@0F8>==>3> B5@;CG52>3> :>=5=B0 G0AB>B0 ;>:>@538>=0@=KE @5F8482>2 4>AB>25@=> C 4,7% ?> A@02=5=8N A 11,1% ?@8 8A?>;L7>20=88 >4=>9 ?@54>?5@0F8>==>9 ;CG52>9 B5@0?88 8 20,0% 2 E8@C@38G5A:>9 3@C??5.  @57C;LB0B5 ?>:070B5;L 157@5F8482=>9 2K68205AB8 A 8A?>;L7>20=85< B5@;CG52>3> :>=5=B0 ?>2KA8;AO 4> 64,9% ?> A@02=5=8N A 55,0% ?@8 >4=>9 ?@54>?5@0F8>==>9 ;CG52>9 B5@0?88 8 44.3% 2 E8@C@38G5A:>9 3@C??5. 7 66 1>;L=KE, 2:;NG5==KE 2 ?@>3@0<;8@048>48D8:0F88, ?@8 B@5E;5B=5:5 =01;N45=8O =5 2KO2;5=> =8 >4=>3> @5F84820 @0:0, 8 ;8HL C >4=>3> ?0F85=B0 (1,5%) 4803=>AB8@>20=K 4K: >20==K9 4 A 8A?>;L7>20=85?5@0F8>==>9 ;CG52>9 B5@0?859 4>;65= 1KBL 4>@0 2 ;5G5=88 1>;L=KE @0:>< ?@O9 :8H:8. @8:0;L=>9 !'-38?5@B5@2KH05B :>;8G5AB2> 1>;L=KE A III AB5?5=LN ;CG52>3> ?0B>@D>70, ?> A@02=5=8N A 8A?>;L7>20=854=>9 ?@54>?5@0F8>==>9 ;CG52>9 B5@0?859. 0;L=59H85 ?5@A?5:B82K 2 C;CGH5=88 @57C;LB0B>2 :>20==>3> 40 ;5G5=8O @0:0 ?@O9 :8H:8 A2O70=K A @50;870F859 ?@>3@0<;8@048>48D8:0F88 A 2:;NG5=85 2 AE5?5@0F8>==>9 ;CG52>9 B5@0?88 =5A:>;L:8E @07=>=0?@02;5==KE @048>48D8:0B>@>2. ABSTRACT Purpose: To enhance the efficiency of preoperative radiotherapy based on application of several radiomodifiers in combined treatment of rectal cancer. Materials and methods: Were analyzed results of surgery and combined treatment of 961 patients included into 3 prospective randomized trials during more 28 years follow-up in Russian Cancer Research Center. 276 patients were treated preoperative radiotherapy (5-Gy fractions daily during 5 days up to total dose 25 Gy, with subsequent surgery for 3-5 days), and 395 was performed only surgery alone. The second protocol enrolled 224 patients (with preoperative termoradiotherapy). Since 2004 for further enhancement of preoperative radiotherapy efficiency was originated program of combined treatment included two radiosensitinogens of tumor cell hypoxic fraction local microwave hyperthermia and electronoacceptor compound of Metronidazolum /M3/, intrarectally, in the form of radiosensitizing intermixture (the patent of the Russian Federation !2234318/2004). The inlet of Metronidazolum was accomplished on the 3-rd, the 4-th and the 5-th sessions before irradiation followed by local microwave hyperthermia. Results: The 5-year outcomes of combined treatment with use preoperative radiotherapy alone were improved at 13,9% due to reduction of locoregional recurrence frequency (from 19,8% in surgery group to 8,7% in combined treatment group). Application of preoperative thermoradiotherapy in patients with distal rectal cancer (middle and lower ampullar parts) reliably decreased the locoregional recurrence frequency up to 4,7% as compared with 11,1% for use preoperative radiotherapy alone and 20,0% in surgery group. As a result recurrence-free survival rate in group of thermoradiotherapy has raised up to 64,9% as compared with 55,0% in preoperative radiotherapy alone and 44,3% in surgery groups. From 66 patients included in the program of polyradiosensitivisation during 2-year follow up was revealed no cancer relapse and for one patient were diagnosed only metastases in the liver. Conclusion: Combined treatment with use of preoperative radiotherapy should to be a method of choice in the treatment of patients with rectal cancer. Application of local microwave hyperthermia enhances amount of patients with the 3-rd grade of radiation pathomorphism as compared with application of preoperative radiotherapy alone, that leads to reduction of locoregional recurrence rate (from 11,1% to 4,7%). 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