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MANAGEMENT OF ESOPHAGEAL CANCER

Elshami Elamin, MD Medical Oncologist Central Care Cancer Center www.cccancer.com Newton, KS - USA. MANAGEMENT OF ESOPHAGEAL CANCER. ESOPHAGEAL CANCER. Risk factors Alcohol / Tobacco Head / neck cancer High fat, low protein & calories Barrett’s Tylosis

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MANAGEMENT OF ESOPHAGEAL CANCER

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  1. Elshami Elamin, MD Medical Oncologist Central Care Cancer Center www.cccancer.com Newton, KS - USA MANAGEMENT OF ESOPHAGEAL CANCER

  2. ESOPHAGEAL CANCER • Risk factors • Alcohol / Tobacco • Head / neck cancer • High fat, low protein & calories • Barrett’s • Tylosis • Plummer Vinson syndrome (Paterson-Brown-kelly Synd) • Achalasia

  3. Symptoms & Signs • Dysphagia • Wt. Loss • Cough • Pain • Hoarseness • Malig pleural effusion, Ascites • Hypercalcemia

  4. Work-Up H&P EGD CBC, CMP CT chest/abd No Mets: Bronchoscopy *Tumor at or above Carina EUS Laparoscopy (GEJ) PET/CT Locoregional I-III/IVA IVB

  5. INTRODUCTION • Surgery has been the raditional management of patients with localised esophageal cancer • Survival is poor, and many pts develop mets or locoregional recurrence soon after surgery

  6. Treatment modalities • Esophagectomy: • Resectable esophageal cancer: • >5 cm from cricopharyngeus • Cervical and cervicothoracic cancer i.e <5 cm from cricopharyngeus should be treated with definitive chemoradiation. • R.T. • Chemotherapy • BSC

  7. Medically Fit • Resectable (>5cm from cricopharyngeus) • Multidisiplinary Eval • Nutritional Assessment (NGT, J-Tube, PEG not recommended) Locoregional I-III/IVA IVB Salvage Therapy • Inresectable: T4 • Medically unfit

  8. GEJ: Celiac nodal involvement may not exclude combined modality therapy • Resectable stage IVA: • Distal esophageal cancer with resectable celiac node • No involvement of aorta or other organ • No involvement of celiac artery • ReseInvctable T4: • Involvement of • Pericardium • Pleura • Diaphragm

  9. Medically Fit • Resectable disease

  10. Endoscopic mucosal resection OR • Esophagectomy Tis, T1a • Medically Fit • Resectable • Esophagectomy (preferred for noncervical) T1b,N0-1 T1b, N1 T2-4, N0-1,Nx M1a (IVA)

  11. Preop Chemo for adeno of distal Esoph or GEJ (ECF) T1b, N1 T2-4, N0-1,Nx M1a (IVA) Definitive ChemoRT PreopChemoRT RT 50-50.4 Gy

  12. Preop Chemo for adeno of distal Esoph or GEJ See Surgical outcome Esophagectomy Salvage esophagectomy for local residual disease PET-CT/CT *EGD Definitive ChemoRT PreopChemoRT RT 50-50.4 Gy PET-CT/CT *EGD *EGD > 5 wks with biopsy or brushings

  13. NED Esophagectomy (preferred) Observe See Surgical outcome PreopChemoRT RT 50-50.4 Gy • Esophagectomy (preferred) • paliative/ (chemo) PET-CT/CT *EGD Persistent local dis unresectable Mets *EGD > 5 wks with biopsy or brushings

  14. Surgical outcomes Tis, T1, N0: observe adeno T2,N0: observe or chemoRT*ECF if given preop (categ 1) N - T3,N0: chemoRT *ECF if given preop (categ 1) Squamous R0 Observe Adenoprox or mid N+ Observe or chemoRT Adeno distal or GEJ chemoRT *ECF if given preop (categ 1) R1 chemoRT R2 chemoRT or palliative

  15. Medically Unfit • Unresectable dis.

  16. Endoscopic mucosal resection OR • ChemoRT Tis, T1a • Medically unfit • unresectable • ChemoRT • Chemo • RT • BSC • Medically unfit • Chemo is tolerable • Unresectable: T4/IVA • Medically unfit • Chemo is not tolerable Palliative RT BSC

  17. ANY SCEINTIFIC EVIDENCE TO SUPPORT THE USE OF CHEMOTHERAPY/R.T. IN LOCALLY ADVANCED OPERABLE ESOPHAGEAL/GASTRIC CANCER?

  18. LITRETURE REVIEW

  19. ADJUVANT THERAPY • Adj RT, chemo, or chemoRT • Mixed results and disappointing • Because trials were small and lacked statistical power • Adj treatment based on 2 or 3-year survival rates • chemoRT and chemo have similar benefits

  20. NEOADJUVANT THERAPY • Due to sig postop complication rate, focus has turned to neoadj treatment. • Currently, there is no evidence to support the use of neoadj RT alone

  21. Any role for Chemo/RT • <30% of locally advanced Gastric/GEJ adeno could be cure with surgery alone • Previous adj chemo failed to show clinical benefit

  22. INT-0116 (SWOG 9008) Adj Option • Randomized lll Trial: • Resectable adeno of stomach • GEJ (lB-IVA) • 5-FU/LVx5d--> RT+5-FU/LV during first 4d and last 3d of RT --> 2cycles of 5-FU/LVx5d • postop CT/RT improve DFS&OS in R0 (resected locally advanced) • [standard of care] • Macdonald et al; N Engl J Med. 2001 Sep 6;345(10):725-30.

  23. The MAGIC TrialThe Medical Research Council Adjuvant Gastric Infusional Chemotherapy • Operable adeno of the stomach, the lower third of the esophagus, and the GEJ ( 74% of pts had tumors in the stomach) • ECFx3->surg->ECFx3 (250 pts) vs Surgery alone (253 pts): • 5Y survival: 36% vs 23% • Chemo sig. improves resectability, PFS and OS Periop. option • D. Cunningham, et al ; N Engl J Med. 2006 Jul 6;355(1):11-20.

  24. Preoperative Chemotherapy vs Surgery Alone FNLCC ACCORD 07-FFCD 9703, multicenter, randomized trial indicated benefit of preoperative chemotherapy vs surgery alone for resectable adenocarcinoma of stomach and lower esophagus[1] Higher rate of R0 resection (87% vs 74%; P = .04) Higher 5-yr OS (38% vs 24%; P = .021) No increase in postoperative morbidity or mortality Boige V, et al. ASCO 2007; Abstract 4510.

  25. Preoperative Chemotherapy vs Surgery Alone Meta-analysis also demonstrated benefit for preoperative chemotherapy in resectable esophageal cancer[2] 5-yr OS benefit of 4.3% (P = .003) 5-yr DFS benefit of 4.4% (P = .0001) Thirion P, et al. ASCO 2007. Abstract 4512.

  26. CALGB 9781 • Only 56 pt with stage I-III • Preop-chemo/RT vs surgery alone • MS 4.5y vs 1.8y • Trimodality imroves survival

  27. Survival benefits from neoadjuvantchemoradiotherapy orchemotherapy in oesophageal carcinoma(meta-analysis)Val Gebski, Bryan Burmeister, B Mark Smithers, KerwynFoo, John Zalcberg, John Simes, for the Australasian Gastro-Intestinal Trials Group Lancet Oncol 2007; 8: 226–34

  28. Meta-analysis • MEDLINE, Cancerlit, and EMBASE databases from major scientific meetings (1980-2006) • Pts with local operable esophageal ca • 10 randomised trials of neoadjuvant chemoRT vs surgery (n=1209) • SCC = 6, adeno =1, both = 3 • 8 of neoradjuvant chemo vs surgery (n=1724) with comparisons • SCC = 7, both = 2

  29. Meta-analysisFindings • The hazard ratio for all-cause mortality with neoadj chemoRT vr surgery • 0·81 (95% CI 0·70–0·93; p=0·002) • corresponding to a 13% absolute difference in survival at 2 years • 0·84 (0·71–0·99; p=0·04) for SCC • 0·75 (0·59–0·95; p=0·02) for adeno • The hazard ratio for neoadj chemo was 0·90 (0·81–1·00;p=0·05) • 2-year absolute survival benefit of 7% • No sig effect on all-cause mortality of chemo for SCC (hazard ratio 0·88 [0·75–1·03]; p=0·12) • Sig benefit for adeno (0·78 [0·64–0·95]; p=0·014)

  30. NEOADJ CHEMO • For SCC, neoadj chemo did not have a survival benefit • hazard ratio for mortality 0・88 [0・75–1・03] • p = 0・12 • For adeno, neoadj chemo showed sig survival benefit (UK Medical Research Council MRC trial) • hazard ratio for mortality 0・78 [0・64–0・95] • P = 0・014

  31. Long term results of the MRC OEO2 randomized trial of surgery with or without preoperative chemotherapy in resectable esophageal cancer • Conclusions: Long term follow-up confirms that preoperative chemotherapy improves survival in operable esophageal cancer and should be considered as a standard of care. • 2002 (Lancet 2002; 359: 1727-33)

  32. NEOADJUVANTCHEMO/RT • Neoadj chemoRT vs surgery • sign benefit over surgery for both histological types • 0・84 (0・71–0・99); p = 0・04 for SCC • 0・75 (0・59–0・95); p = 0・02 for adeno

  33. Sequential vs Concurrent chemoRT • No survival benefit of sequential chemoRT in SCC • hazard ratio for mortality 0・90 [0・72–1・03]; p=0・18) • similar to SCC treated with neoadj chemo • Concurrent chemoRT had sig benefit for both histological types • hazard ratios 0・76 and 0・75 for SCC and adeno, respectively

  34. Meta-analysisInterpretation • A signifi cant survival benefi t was evident for preoperative chemoradiotherapy and, to a lesser extent, for chemotherapy in patients with adenocarcinoma of the oesophagus.

  35. MDACC study: Salvage Resection for Esophageal Carcinoma: OS • No difference in OS between salvage and planned resection • 5-year survival 46% for salvage vs 42% for planned resection OS 1.0 Planned surgery 0.8 Salvage 0.6 Cumulative Survival Probability 0.4 P = .125 0.2 0.0 60 0 30 50 10 40 20 Months Median follow-up: 24 months Hofstetter WL, et al. GI Cancers Symposium 2009. Abstract 7.

  36. THANKS

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