Esophageal Caner       Ahmed Zeeneldin  Ass. Prof Medical Oncology           NCI-           NCI-Cairo             2009    ...
Case Scenarion   Malen   65 yearsn   CO: dysphagian   How will you proceed?                               2
n   What are the causes of dysphagia?                           dysphagia?n   What about male 65 y?                       ...
Esophageal AnatomyUpper Esophageal Sphincter (UES)        Esophageal Body        18 to 24 cm       (cervical & thoracic)Lo...
Tumor as seen via endoscope      endosonography                              5
Histology of esophagus                         6
7
Epidemiology                                   Worldwide    Worldwide estimates for 2000n   Eight most common cancer    wi...
Epidemiology                                       US    US estimates for 2005    • 14,520 new cases    - 11,220 male    -...
Incidence in Egypt                     year 2002n   0.8% of all cancersn   19th in males and 22nd in femalesn   Male to fe...
NCI Cairon   1.3 % of all cancersn   Male: female: 1.7:1n   Median age 60 y                           NCI report (2002, 20...
LNs along the esophagus                          12
Stagingn   T:    n    1:          n   1a: Lamina Propria or          n   1b: submucosa    n    2: Musclaris    n    3: Adv...
14
Stage grouping           T1         T2           T3         T4         M1                                                 ...
Prognostic factorsn   Definition:n   Stage: TNMn   Weight lossn   C-reactive protein* [Ikeda, Ann surg, 2003, 238: 179]   ...
Work-                         Work-upn   H&Pn   EGD (+Bx)          (+Bx)n   CT Chest and Abdomen e contrastn   CBCD and ch...
Treatmentn   Multidisciplinary evaluation:    n Surgeon    n Medical oncologist    n Radiation oncologist    n Radiologist...
Outcome of initial assessmentn   Metastatic (Stage IV B) = M1b                                M1n   Very early    (stage I...
Stage IVB (metastatic)n   Performance status:    n PS >2: BSC         >2    n PS 0-2: BSC +/- CTh                  +/-    ...
Metastatic EC                21
BSCn   Dysphagia:    Dysphagia:    n   Restore lumenal passage         n Endoscopic: dilatation, stent, Laser         n Ra...
Chemotherapyn   Primary :    n Metastatic setting, stage IVB    n Regimen: CFn   Pren   Postn   Peri (pre and post)       ...
Chemotherapy for metastatic diseasen   Compared to adenoCA,    n   SCC is more sensitive to chemo, radio, and chemoradiati...
Agentsn   Cisplatin: 20%    Cisplatin: 20% RRn   Older:    n   5FU           Doxo         MTX    n   Mitomycin     Bleomyc...
Combinations               cisplatin-               cisplatin-containingn   Cisplatin-    Cisplatin- 5FU (CF):            ...
Non-        Non-Cisplatin combinationsn   Irinotecan- FU-    Irinotecan-5FU-LV:       RR 29% in platinum                  ...
Phase III trialsn   German study groupn   Metastatic GE CAn                    FLO vs.        FLP:n   Overall:    n   Less...
Phase III trialsn   REAL-    REAL-2 trialn   1002 patients with advanced GE CA (30% E)                                    ...
Phase IIàIII trial                   IIàn   Inoperable E CAn                 FOLFOX4                  FOLFOX4 vs.  CFn   M...
Very early (stage I)                   T1 & N1/Nx & M0                        N1        M0n   Tis and T1a: Lamina propria ...
Post-     Post-esophagectomy therapyn   Depends on:    n R (residual): R0= no, R1 = microscopic, R2 =macro                ...
Post-        Post-esophagectomy therapyn   R2:    n   chemoradiation (fluoropyrimidine based) or    n   palliative therapy...
Stage II-IVA                                  II-    (Loco-    (Loco-regionally advanced, M1a, N1, T2-T4)                 ...
Some scenariosn   Irresectable:    Irresectable: chemoradiation then assess    resectabilityn   Unfit for surgery or Refus...
Stage II-VIA, resectable and fit      II-                                   36
Stage II-IVA                         II-    (Loco-    (Loco-regionally advanced, M1a, N1, T2-T4)                          ...
Surgeryn   Gold standardn   All patients should be assessed for respectabilityn   Considered for    n   ALL    n   FIT    ...
Surgeryn   Type of surgery:    n   Tumor location    n   Surgeon: experience and preference    n   Patient preferencen   I...
Limitations of surgeryn   Resection of tumor and nodesn   Margin: circuferential and longitudinaln   Anatomic locationn   ...
Radiotherapyn   Definitive and palliativen   Pre- post-    Pre- or post-operativen   Types:    n External beam (EB)    n B...
Combined modality treatment                              42
Peri-Peri-operative CT                    43
MAGIC trial              44
n   MRC (MAGIC trial)n   Resectable gastric (74%) , lower esophagus (14%),                       (74%)                   (...
Neoadjuvant chemotherapy                           46
Neoadjuvant chemotherapy                      Randomized TrialsStudy (year)       Patients    Chemotherapy       pCR (%)  ...
Preoperative CTn   RTOG 8911 (INT 0113)                     0113)n   Potentailly resctable E CAn            S vs CT (CF)àS...
Preoperative CTn   MRC OEO2 (INT 0113)         OEO2        0113)n   802 Potentially resctable E CAn                  S vs ...
Preoperative CTn   French study group (FFCD 9703)                               9703)n   244 Potentially resectable lower ...
Neoadjuvant chemotherapy                    Meta-                    Meta-analysisCochrane Database 2003n   11 Randomized ...
Neoadjuvant Chemoradiotherapy                                52
Non-               Non-Randomized Trialsn   46 trials from 1981 to 1999n   2704 patients – 69% SCC, 31% Adenocarcinoma    ...
Randomized TrialsStudy             Patients        Histology   Chemotherapy       Surgical        pCR (%)   Median        ...
Primary CRTn   RTOG 85-01          85-n   Esophageal squamous or adenocarcinoman   T1-3 N0-1 M0n   RT (64Gy 2x32): # 62   ...
n   RTOG 85-01 results           85-            CRT         RTn   5yOS       26       0     %n   Residual 26         37 %n...
INT 0123 trialn   Follow up of RTOG 85-01                      85-n   CF+    n LD RT: 50 Gy    n HD RT: 64 Gyn   No differ...
Preoperative CRTn   Resectable CA and fit patient:    n Most common    n Still investigationaln   Unresectable    n   May ...
Surgery vs. CRTà Surgery                      CRTà                CALGB 9781n   Stage I-III          I-n   # 56n          ...
Post-            Post-operative CRTn   Resectable adeno CA of stomach and GEJn   #556n                   S     vs S+CRT (F...
Neoadjuvant CRT Meta-analyses                             Meta- Urschel J, Am J Surg 2003; 185: 538-543                   ...
The Role of Surgery after Chemoradiotherapy                                                                     OSGOCSG St...
Initial management                     63
64
Conclusions              65
n   EC is a rare diseasen   Male predominancen   Old agen   Poor outcomen   Surgical constrains and secondary tumor effect...
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Esophageal caner ahmed md [compatibility mode]

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Comprehensive overview of esophageal carcinoma: diagnosis, staging and treatment

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Esophageal caner ahmed md [compatibility mode]

  1. 1. Esophageal Caner Ahmed Zeeneldin Ass. Prof Medical Oncology NCI- NCI-Cairo 2009 1
  2. 2. Case Scenarion Malen 65 yearsn CO: dysphagian How will you proceed? 2
  3. 3. n What are the causes of dysphagia? dysphagia?n What about male 65 y? 3
  4. 4. Esophageal AnatomyUpper Esophageal Sphincter (UES) Esophageal Body 18 to 24 cm (cervical & thoracic)Lower Esophageal Sphincter (LES) 4
  5. 5. Tumor as seen via endoscope endosonography 5
  6. 6. Histology of esophagus 6
  7. 7. 7
  8. 8. Epidemiology Worldwide Worldwide estimates for 2000n Eight most common cancer with 412,000 new cases 412,n Sixth most common cause of cancer death with 338,000 338, deathsn 2002 update 462, 462,000 new cases 386, 386,000 deathsParkin DM, Lancet Oncol 2001; 2: 533-543Parkin DM, CA Cancer J Clin. 2005;55:74-108 8
  9. 9. Epidemiology US US estimates for 2005 • 14,520 new cases - 11,220 male - 3,300 female • 13,570 deaths 9Jemal A CA Cancer J Clin. 2005;55:10-30
  10. 10. Incidence in Egypt year 2002n 0.8% of all cancersn 19th in males and 22nd in femalesn Male to female: 1.9:1n Median age 60 yearsn Site: U (10%), M (20%), L (61%), ? (10%), (20%), (61%),n Pathology: n SCC: 65% 65% n Adeno: 22% 22% GPCR (2007) (2007) 10
  11. 11. NCI Cairon 1.3 % of all cancersn Male: female: 1.7:1n Median age 60 y NCI report (2002, 2003) (2002, 2003) 11
  12. 12. LNs along the esophagus 12
  13. 13. Stagingn T: n 1: n 1a: Lamina Propria or n 1b: submucosa n 2: Musclaris n 3: Adventitia n 4: adjacentn N: n 1: regional LNn M: n 1a: cervical LN in upper thoracic esoph, esoph, celiac LN in lower thoracic eso n 1b: other distant sites 13
  14. 14. 14
  15. 15. Stage grouping T1 T2 T3 T4 M1 (a/b)N0 I IIA IIA III IV (a/b)N1 IIB IIB III III IV (a/b) IV (a/b) IV (a/b) IV (a/b) IV (a/b) IV (a/b)M1(a/b)5y OS 1: 80 2a: 40 3: 10 4a: <5 <5 2b: 20 4b: <1 <1 15
  16. 16. Prognostic factorsn Definition:n Stage: TNMn Weight lossn C-reactive protein* [Ikeda, Ann surg, 2003, 238: 179] 2003, 238: 179]n Others: n PS n Age n Comorbidities n Sex n others 16
  17. 17. Work- Work-upn H&Pn EGD (+Bx) (+Bx)n CT Chest and Abdomen e contrastn CBCD and chemistryn Barium swallow (optional)n If no M1: M1 n Bronchoscopy (T at/above carina) n EUS n Laparoscopy (T at EG junction) n PET n Biopsy of suspected M1 disease M1 17
  18. 18. Treatmentn Multidisciplinary evaluation: n Surgeon n Medical oncologist n Radiation oncologist n Radiologist n Gastroenterologist n pathologist 18
  19. 19. Outcome of initial assessmentn Metastatic (Stage IV B) = M1b M1n Very early (stage I): T1 & N0/Nx & M0 N0 M0n loco- loco-regionally advanced (Stage II, III,IVA) (Stage M1a or N1 or T2-T4) N1 T2Factors that govern decision • Tumor extent: resectable or not • Patient: • Choice • Fitness for radical surgery • Fitness for chemoradiation • Clinical setting: • Surgical expertise and facilities • Medical and radiation oncology expertise and facilities 19
  20. 20. Stage IVB (metastatic)n Performance status: n PS >2: BSC >2 n PS 0-2: BSC +/- CTh +/- 20
  21. 21. Metastatic EC 21
  22. 22. BSCn Dysphagia: Dysphagia: n Restore lumenal passage n Endoscopic: dilatation, stent, Laser n Radiotherapy: EBRT, Brachtherapy n Chemotherapy n Bypass the obstruction n Stoma: gastrostomy*, jejenostomy gastrostomy*, n Surgeryn Painn bleeding 22
  23. 23. Chemotherapyn Primary : n Metastatic setting, stage IVB n Regimen: CFn Pren Postn Peri (pre and post) 23
  24. 24. Chemotherapy for metastatic diseasen Compared to adenoCA, n SCC is more sensitive to chemo, radio, and chemoradiation n But the long term outcome is the samen Evolvingn No powered phase III trialsn No survival benefitn Improves QOLn No preference of any specific regimen 24
  25. 25. Agentsn Cisplatin: 20% Cisplatin: 20% RRn Older: n 5FU Doxo MTX n Mitomycin Bleomycinn Newer: n Docetaxel Paclitaxel Irinotecan n Oxaliplatin Capecitabinen Targeted: n Gefitinib Erlotinib Cetuximab 25
  26. 26. Combinations cisplatin- cisplatin-containingn Cisplatin- Cisplatin- 5FU (CF): RR 20-50% 20-50%n Paclitaxel- cisplatin- Paclitaxel- cisplatin- 5FU (PCF): SCC and Adenon Irinotecan-cisplatin: Irinotecan-cisplatin: SCCn Docetaxel-cisplatin-irinotecan: Docetaxel-cisplatin-irinotecan: RR 63% (ph II, #16) 63% #16)n Gemcitabie-cisplatin: Gemcitabie-cisplatin: RR 45% 45%n Mitomycin- cisplatin- Mitomycin- cisplatin- 5FU (MCF) equivalent to epirubicin-cisplatin- epirubicin-cisplatin- 5FU (ECF): EG CA, lower QOLn Capecitabine regimens (ECX) 26
  27. 27. Non- Non-Cisplatin combinationsn Irinotecan- FU- Irinotecan-5FU-LV: RR 29% in platinum 29% resistantn Paclitaxel- Paclitaxel- carboplatin: RR 43% (neutropenia 43% G3,4 52%) 52%)n Oxaliplatin regimens (EOX, EOP)n Capecitabine 27
  28. 28. Phase III trialsn German study groupn Metastatic GE CAn FLO vs. FLP:n Overall: n Less toxicity n PFS: 5.8 vs. 3.9 m* (trend) n OS: 10. 10.7 vs. 8.8 (NS)n Over 65 years: n RR: 41 vs 17% 17% n TTF: 5.4 vs 2.3 m n PFS: 6 vs 3m n OS: 14 vs 7m Al- Al-Batran JCO 26(9). 2008` 26( 2008` 28
  29. 29. Phase III trialsn REAL- REAL-2 trialn 1002 patients with advanced GE CA (30% E) (30%n Adeno, Adeno, SCC, or undifferentiatedn ECF, ECF, EOF, ECX, EOXn RR: 41 42 46 58 %n 1YOS: 38 40 41 47% 47%n EOX>>>ECFn Xeloda= Xeloda= 5FUn Oxali = Cisplatin Cuningham NEJM 358(1). 2008 358( 29
  30. 30. Phase IIàIII trial IIàn Inoperable E CAn FOLFOX4 FOLFOX4 vs. CFn Median OS 22.722. 14. 14.7 mn Median TTP 15 9.5 mn Median EFS 11.6 11. 7.8 M Conory ASCO 2007 # 4532 30
  31. 31. Very early (stage I) T1 & N1/Nx & M0 N1 M0n Tis and T1a: Lamina propria T1 n Endoscopic mucosal resection n Ablation n Esophagectomy n (non- (non-cervical, > 5 cm from cricopharyngeus muscle)n T1b : n Esophagectomy ( as above) 31
  32. 32. Post- Post-esophagectomy therapyn Depends on: n R (residual): R0= no, R1 = microscopic, R2 =macro R0 R1 R2 n Histology n LN status n Site n T stage 32
  33. 33. Post- Post-esophagectomy therapyn R2: n chemoradiation (fluoropyrimidine based) or n palliative therapyn R1: n chemoradiation (FPB)n R0: n Squamous (N+, N-): observe N- n Adenocarcinoma: Adenocarcinoma: n N+: n proximal or mid E: observe or chemoradiation n distal E or EGJ : chemoradiation or chemo (ECF if given preoperative) n N-: n Tis /T1: observe /T1 n T3/4: chemoradiation n T2: observe or chemoradiation 33
  34. 34. Stage II-IVA II- (Loco- (Loco-regionally advanced, M1a, N1, T2-T4) M1 N1 T2n Site and histology n Distal E/EG junction AND adenocarcinoma: adenocarcinoma: n Neo- Neo-adjuvant chemo therapy n ECF x 3 ->Surgery -> ECF x 3 n Other sites or squamous histology: n Neo- Neo-adjuvant or definitive Chemo-radiation Chemo- n Definitive: Definitive: followed by observation or palliative surgery n Neo-adjuvant: Neo-adjuvant: to be followed by radical surgery if CR or PR or palliative therapy/ BSC if SD or PD 34
  35. 35. Some scenariosn Irresectable: Irresectable: chemoradiation then assess resectabilityn Unfit for surgery or Refused surgery n Chemoradiation (FPB)n Unfit for chemoradiation: radiotherapy alone chemoradiation:n Unfit for radiotherapy: chemon Unfit for any thing: BSC 35
  36. 36. Stage II-VIA, resectable and fit II- 36
  37. 37. Stage II-IVA II- (Loco- (Loco-regionally advanced, M1a, N1, T2-T4) M1 N1 T2n Applicable to resectable: resectable: n T: Tis- T4 (some T4 are unresectable) Tis- T4 unresectable) n N: 0,1,X n M1a: cervial and celiac LN (some M1 celiac are M1 unresectable ) 37
  38. 38. Surgeryn Gold standardn All patients should be assessed for respectabilityn Considered for n ALL n FIT n RESECTABLE n Abdominal and thoracic (> 5 cm from cricopharyngyeus m) n NB: cervical and thoracic < 5cm CPM: definitive CRT 38
  39. 39. Surgeryn Type of surgery: n Tumor location n Surgeon: experience and preference n Patient preferencen Indications: n Tis T1a (mucosa): EMR, ablation, surgery n T1b, T2, T3: surgery T2 T3 n T4 (pericardium, pleura or diaphragm): resectable n NB: irresectable T4 (heart, great vessels, trachea, liver, spleen, pancreas, lung): : CRT n N1: resectable (LN#=15) (LN#=15) n M1a lower esophagus and resectable celiac LN n NB: M1b: systemic treatment M1 39
  40. 40. Limitations of surgeryn Resection of tumor and nodesn Margin: circuferential and longitudinaln Anatomic locationn Restoration of continuity 40
  41. 41. Radiotherapyn Definitive and palliativen Pre- post- Pre- or post-operativen Types: n External beam (EB) n Brachytherapy (BT): n Palliation n Not superior to EB 41
  42. 42. Combined modality treatment 42
  43. 43. Peri-Peri-operative CT 43
  44. 44. MAGIC trial 44
  45. 45. n MRC (MAGIC trial)n Resectable gastric (74%) , lower esophagus (14%), (74%) (14%), EGJ (11%) (11%)n S vs ECFx3àSàECFx3 ECFx3 ECFx3n # 253 250n 5y OS 23 36% 36%n PFS HR 0.66n Down- Down-stagingCunningham N Engl J M 355(1). 2006 355( 45
  46. 46. Neoadjuvant chemotherapy 46
  47. 47. Neoadjuvant chemotherapy Randomized TrialsStudy (year) Patients Chemotherapy pCR (%) Median 5-year P value Survival (mo) Survival (%)Roth (1988) (1988) C + S 19 Neo: C,Vin, Bleo NA 9 NA NS S 20 Adjuvant: C, Vin 9 NANygaard (1992) (1992) C + S 50 C, Bleo NA 8 3-y 3 NS S 41 8 9Ancona (2001) (2001) C + S 47 CF X 2 or 3 13% 13% 25 34 NS S 47 24 22Schlag (1992) (1992) C + S 22 CF X 3 NA 10 NA NS S 24 10INT 0113 (1998) 1998) C + S 213 Neo CF X 3 2.5% 14. 14.9 2 y 35 NS S 227 Adj CF X 2 16. 16.1 37MRC (2002) (2002) C + S 400 CF X 2 4% 16. 16.8 2 y 43 P = 0.004 S 402 13. 13.3 34 47
  48. 48. Preoperative CTn RTOG 8911 (INT 0113) 0113)n Potentailly resctable E CAn S vs CT (CF)àS (CF)àn OS samen R0 59 63 %n R1 15 4 % 48
  49. 49. Preoperative CTn MRC OEO2 (INT 0113) OEO2 0113)n 802 Potentially resctable E CAn S vs CT (CFx2 )àS (CFx2n Median OS 13.3 16.8 m 13. 16.n 6yOS 17 23 % 49
  50. 50. Preoperative CTn French study group (FFCD 9703) 9703)n 244 Potentially resectable lower E & G CAn S vs CT (CF )àS )àn 5y PFS 21 34 %n 5yOS 24 38 % 50
  51. 51. Neoadjuvant chemotherapy Meta- Meta-analysisCochrane Database 2003n 11 Randomized trials involving 2051 patientsn Clinical relevance based on median survival and 1 to 5 year survivaln When specific survival was not available, it was calculated from the published survival curves- Pooled response rate to chemotherapy was about 36% 36% with 3% pCR- No difference in survival at 1 and 2 years- Survival advantage starts at 3 years and reaches statistical significance at 5 yearsCochrane Database Syst Rev 2003; 4: CD001556 2003; CD001556 51
  52. 52. Neoadjuvant Chemoradiotherapy 52
  53. 53. Non- Non-Randomized Trialsn 46 trials from 1981 to 1999n 2704 patients – 69% SCC, 31% Adenocarcinoma 69% 31%n RT dose from 30 to 60 Gyn Majority of studies used 5-FU and cisplatinn Resection rate 74% 74%n Pathologic CR: 24% (32% surgical patients) 24% (32%n Patterns of recurrence after surgical resection - Locoregional 9% - Distant 31% 31% - Both 6%Geh JI, Br J Surg 2001; 88:338-356. 53
  54. 54. Randomized TrialsStudy Patients Histology Chemotherapy Surgical pCR (%) Median 3-year survival (%) P value RT mortality (%) Survival (mo)Nygaard (1992) (1992) S 41 S Cis + Bleo 13 NA 7.5 9 NS CS 47 35 Gy 24 7.5 17Le Prise (1994) (1994) S 45 S Cis + 5-FU 7 10 10 14 NS CS 41 20 Gy 8.5 10 19Apinop (1994) (1994) S 34 S Cis + 5-FU 15 7 20 NS CS 35 40 Gy 14 10 26Walsh (1996) (1996) S 55 A Cis + FU 4 22 11 6 P = 0.01 CS 58 40 Gy 8 16 32Law (1998) (1998) S 30 S Cis + 5-FU 0 25 27 NA NS CS 30 40 Gy 0 26 NABosset (1997) (1997) S 139 S Cis 4 26 19 37 NS CS 143 37 Gy 12. 12.3 19 39Urba (2001) (2001) S 50 S (25%) (25%) Cis + 5-Fu + Vin 2 28 18 16 NS CS 50 A (75%) (75%) 45 Gy 7 17 30Burmeister S 128 S (36%) (36%) Cis + 5-FU NA 15% 15% 22 NA NS(2002) 2002) CS 128 A (61%) (61%) 35 Gy 19 NA 54
  55. 55. Primary CRTn RTOG 85-01 85-n Esophageal squamous or adenocarcinoman T1-3 N0-1 M0n RT (64Gy 2x32): # 62 (64Gy 32):n CRT: # 134 RT (50 Gy 2x25)+ CF (Cd1 F d1-4 q 4w x 3) (50 25)+ (Cd1 d1 n Cis: Cis: 100 mg/m2/d2 (cis 50mg/m2 d1 and d8) mg/m2/d2 50mg/m2 d8 n FU: 800 mg/m2/d1-4 CI mg/m2/d1 n Q 4 or 3 wks n For 2-3 cycles 55
  56. 56. n RTOG 85-01 results 85- CRT RTn 5yOS 26 0 %n Residual 26 37 %n Life- Life-threatening toxicityn 10 2 %n acute tox High lown Late tox same same 56
  57. 57. INT 0123 trialn Follow up of RTOG 85-01 85-n CF+ n LD RT: 50 Gy n HD RT: 64 Gyn No difference in OS or treatment failure 57
  58. 58. Preoperative CRTn Resectable CA and fit patient: n Most common n Still investigationaln Unresectable n May facilitate resectionn Resectable but unfit: definitive CRT 58
  59. 59. Surgery vs. CRTà Surgery CRTà CALGB 9781n Stage I-III I-n # 56n CRTS Sn Median OS 4.5 1.8 yn 5yOS 39 16 % Tepper JCO 26(7). 2008 26( 59
  60. 60. Post- Post-operative CRTn Resectable adeno CA of stomach and GEJn #556n S vs S+CRT (FU/LV)n Median OS 27 36 mn 3yOS 41 50 %n 3yRFS 31 48 %n Significant in high recurrence risk 60
  61. 61. Neoadjuvant CRT Meta-analyses Meta- Urschel J, Am J Surg 2003; 185: 538-543 2003; 185: 538- - - Neoadjuvant chemoradiation improves 3-year survival, with more significant benefit in the concurrent studies (OR 0.45, 45, 95% 95% CI 0.26 to 0.79, p = 0.005) 79, 005) - - Decrease LR but not distant recurrences Fiorica F, Gut 2004;53: 925-930 2004;53: 925- - - Neoadjuvant chemoradiotherapy significantly reduces the 3- year mortality rate (OR 0.53, 95% CI 0.26 to 0.72, p = 0.03) 53, 95% 72, 03) - - Risk of postoperative mortality is higher in the neoadjuvant group ( OR 2.10, 95% CI 1.18-3.73, p = 0.01) 10, 95% 18- 73, 01) Greer SE, Surgery 2005; 137: 172-177 2005; 137: 172- - - Neoadjuvant chemoradiotherapy is associated with a small, non- non-statistically significant improvement in overall survival (RR of death in neoadjuvant group 0.86, 95% CI 0.74 to 1.01, p 86, 95% 01, = 0.07) 07) Malthaner RA, BMC Med 2004; 2: 35 2004; - A significant difference in the risk of mortality at 3-years favors neoadjuvant chemoradiation (RR 0.87, 95% CI 0.80-0.96, p 87, 95% 80- 96, =0.004) 004)*None of the meta-analysis included Burmeister’sstudy, which has been recently published (Lancet Oncol2005) and at that time was available only in abstractform 61
  62. 62. The Role of Surgery after Chemoradiotherapy OSGOCSG Stahl M, J Clin Oncol 2005; 23:: 2310--2317 2005; 23 2310FLEP X 3 → EP + 40 Gy → surgery (89 patients) (89FLEP X 3 → EP + > 66Gy 66Gy (88 patients) S CRT S CRT3-year OS 31. 31.3% 24. 24.4%Median survival 16. 16.4 m 14. 14.9 m FLRP- CRT resulted in equivalent survival with preserved esophagus- Surgery significantly increased local control S- Survival curves appear to spread after 3 years but without reaching statistical significance- Patients responding to induction therapy appear to have good CRT prognosis regardless of surgical intervention 62
  63. 63. Initial management 63
  64. 64. 64
  65. 65. Conclusions 65
  66. 66. n EC is a rare diseasen Male predominancen Old agen Poor outcomen Surgical constrains and secondary tumor effectsn CT in met disease has little survival benefit (CF, EOX, FOLFOX)n Multimodality therapy is very essentialn CCRT supersedes C and RT alone and can be used as definitive, preoperative or post operative modalityn BSC is important 66

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