esophagus carcinoma management updated NCCN

on ca pancrease

1. Management of esophageal carcinoma Presented By: DR M Umair Radiation Oncology .

2. Four regions of the esophagus: Cervical C6-T2 Cricoid cartilage to thoracic inlet (15–18 cm from the incisor). Thoracic T3-T11 Upper thoracic = thoracic inlet to lower border of the azygos vein (18–24 cm). Midthoracic = lower border of the azygos vein to inferior pulmonary veins (24–32 cm). Lower thoracic/GEJ = ge junction (32–40 cm). Abdominal=ge to 2 cm below GEJ .

3. Keep in mind, Suclear notes are M1 for GE junction tumor and vice versa

4. Histologically 4 layers: Mucosa Submucosa Muscular Fibrous layer No serosa .

5. Pattern of spread No serosal covering , direct invasion of contiguous structures occurs early. Usually locally advanced at presentation. Commonly spread by lymphatics (70%) Lymph node involvement increases with T stage. T1a / T1b / T2 of 7→ 20→ 40% 25% - 30% hematogenous metastases at time of presentation. Most common site of metastases are lung, liver, pleura, bone, kidney & adrenal gland Median survival with distant metastases – 6 to 12 months . ‘’ Crocodiles have serosa “ Apparently they don’t get cancer

6. Siewert et al TYPE I Up to 5 cm above GEJ TYPE II 1cm above /2cm below GEJ TYPEIII >2cm below GEJ .

7. Epidemiology 6 th most common cause of cancer related death Most common in China, Iran, South Africa, India and the former Soviet Union. Globally 70% cases are squamous cell carcinoma The incidence rises steadily with age, reaching a peak in the 6 th to 7 th decade of life. Male : Female =4: 1 lifetime risk 0.5% .

8. Types of Esophageal Cancer Squamous cell carcinoma Upper and middle thirds of the thoracic esophagus adenocarcinoma Distal esophagus. .

9. DIFFERENCE B/W SCC AND ADENOCA Decreasing in USA Tobacco alcohol Epithelial dysplasia 10 years earlier High perioperative mortality locoregionally recurrence Poorer Higher Increasing GERD intestinal metaplasia/ BMI later Lower than Distant Better prognosis than SCC lower prevalence of lymphatic spread .

10. Risk Factors : Squamous Cell Carcinoma Smoking and alcohol (80% - 90%) Dietary factors N-nitros compounds (animal carcinogens) Pickled vegetables and other food-products Toxin-producing fungi Betel nut chewing Ingestion of very hot foods and beverages (such as tea) Underlying esophageal disease PVS(UPPER1/3 RD ) ACHALASIA TYLOSIS PALMARIS COELIAC DISEASE .

11. Risk Factors: Adenocarcinoma Associated with Barretts’s esophagus, GERD & hiatal hernia. Obesity (3 to 4 fold risk) Smoking (2 to 3 fold risk) Increased esophageal acid exposure such as Zollinger-Ellison syndrome. Fig. Barretts’s esophagus Barrett’s esophagus is a metaplasia of the esophageal epithelial lining. The squamous epithelium is replaced by columnar epithelium,with 0.5% annual rate of neoplastic transformation. .

12. Prevention A recent large prevention study, AspECT, evaluated this question for patients with Barrett esophagus # 1 cm and no HGD or esophageal adenocarcinoma.38 A total of 2,563 patients were randomly assigned to high-dosage (40 mg twice daily) or low-dosage (20 mg once daily) esomeprazole proton-pump inhibitor acid suppression, alone or combined with 300 mg of aspirin per day. primary composite end point was time to all-cause mortality, esophageal adenocarcinoma, or HGD. The use of a high-dose proton pump inhibitor, especially in combination with aspirin, substantially improved outcomes for patients with Barrett esophagus

13. Diagnostic Workup Upper GI endoscopy + biopsy: allow direct visualization and biopsy, measure proximal & distal distance of tumor from incisor, presence of Barrett’s esophagus. Best modality for T staging ; better than CT and PET Best also for nodal staging as CT and PET have lower sensitivity Early, superficial cancer Circumferential ulceration esophageal cancer Malignant stricture of esophagus .

14. Esophageal luminal diameter of <= 13 mm results in dysphagia. Scenario Preferred Option Imminent obstruction Stent Life expectancy <3 mo Stent Life expectancy >3 mo RT (EBRT or brachytherapy) Proximal tumor RT (avoid stent near trachea) Recurrent dysphagia post-RT Stent Key Studies SEMS vs. RT: Stents provide faster relief but higher complications (Javed et al., Gastrointest Endosc 2012). Brachytherapy has better long-term dysphagia control (Rosenblatt et al., Int J Radiat Oncol 2010). Dutch SIREC Trial: Stents had more complications than brachytherapy (Homs et al., Gastroenterology 2004). CT SCAN

15. Scenario Preferred Option Imminent obstruction Stent Life expectancy <3 mo Stent Life expectancy >3 mo RT (EBRT or brachytherapy) Proximal tumor RT (avoid stent near trachea) Recurrent dysphagia post-RT Stent Key Studies SEMS vs. RT: Stents provide faster relief but higher complications (Javed et al., Gastrointest Endosc 2012). Brachytherapy has better long-term dysphagia control (Rosenblatt et al., Int J Radiat Oncol 2010). Dutch SIREC Trial: Stents had more complications than brachytherapy (Homs et al., Gastroenterology 2004).

16. Compare sensitivity of EUS with CT and PET

17. Patterns of Failures No survival Difference- SCC vs Adeno Occult Mets invariably present- 30% skip mets DISTANT FAILURE – Major Issue Lung, Liver, Bone mets predicted by DOI +ve LN dissemination Upper, middle – local recurrence Distal- distant failure prominent Pattern of failure – should improve systemic treatment . 5Yr OS 40% confined to primary 20% LN+ 4% mets

18. Major issue in esphageal carcinoma management No serosa → Esophageal cancer is more aggressive (no natural barrier). Adventitia → Anchors the esophagus but doesn’t stop tumors. Result: Higher local recurrence rates, challenging surgeries, and need for multimodal therapy.

19. EC limited to the mucosa (HGD or tumors invading the lamina propria or muscularis mucosae; T1a may be managed with endoscopic resection (endoscopic mucosal resection or endoscopic submucosal dissection) because there is a relatively low risk (2%) of occult regional LN metastasis. For lesions that have penetrated the submucosa without LN involvement on staging studies (tumor invading the submucosa; T1b), surgical resection with lymphadenectomy is recommended because of the approximately 15% to 40% risk of occult LN involvement Basic paradigm

20. For any lesions at least T3 (tumor invading the muscularis propria; T3) and/or node-positive disease amenable to surgical resection, multimodal management with chemotherapy or chemotherapy with concurrent radiation therapy, before and/or after surgery, has become the standard, given the high risk of micrometastastic dissemination It is controversial whether all patients with T2N0 GEC (ie, tumor invading the muscularis propria; T2 should receive perioperative or neoadjuvant therapy and surgery versus surgery alone, because some studies have included such patients as eligible and other studies have not, and some reports have suggested a lack of benefit in the setting of adequate surgery.Currently, a discussion of potential risks and benefits of perioperative therapy and surgery versus surgery alone with the patient and family is prudent, and a personalized approach for patients with T2N0 disease is recommended, including enrollment in a clinical trial if available.

21. Criticism of ESOPEC; CROSS arm results don’t match results from CROSS study So it is implicated that maybe protocol was not followed

22. FFCD & Stahl both for 60- 66 GY CROC also has 60 GY.. while SANO has lesser dose

23. KEYNOTE 975 Concept; as per cross trial we can see that mostly local control is very good with CCRT and mostly there are distant metastsis at failure. Additional treatment is needed to combat this for which trial was designed. Presented last year and shows OS benefit Hazard Ratio (HR): The hazard ratio for death was 0.72 (95% CI, 0.59-0.89); p=0.002). This means there was a 28% reduction in the risk of death with the pembrolizumab regimen. Median Overall Survival: The median OS was not reached in the pembrolizumab group vs. 16.9 months in the placebo group. Progression-Free Survival (PFS): Also significantly improved, with a HR of 0.73 (95% CI, 0.59-0.90).

24. KEYNOTE 585 & MATTERHORN

25. Treatment Groups Early Tis ( HGD ) / T1a /superficial T1b(<2cm ,no LVI)(AC) Localized disease T1b-T2 Node negative(<3cm GdI) Locally advanced disease (T1bN1-T4a Any N) Locally advanced unresectabale Cervical esophagus Metastatic .

26. Pre-malignant ( HGD )/ T1a .

27. Early Tis ( HGD ) / T1a /superficial T1b(<2cm ,no LVI)(AC) Endoscopic therapy ER If completely excised ER followed by ablation Residual dysplasia Ablation Exclusively for Barrets/Tis Surveillance Serial endoscopy 6 weeks later Multiple 4 quadrants biopsy at 1-2 cm interval T1b CTC/A/P annually for 3 years . 3 MONTHLY YEAR1 6 MONTHLY YEAR2 ANNUALLY INDEFINITELY Diagnosed on ER specimen

28. Localized disease T1bNO .

29. Localized disease T1b- T2 Node –ve ,<3cm Gd1 UPFRONT ESOPHAGECTOMY Adjuvant Rx: See Histology type SqCCa: R0 (irrespective of Nodal Status) 🡪 Observation Margin +ve 🡪 CCRT Adeno Ca: CCRT N+ Margin +ve No Rx N0 .

30. FOLLOWUP Pts who underwent esophagectomy surveillance H & PE CTC/A annually for 3 years ENDOSCOPY based on symptoms and radiographic findings Pts who underwent esophagectomy 🡪CCRT H & PE CTC/A q6monthly for 2 yrs .

31. Locally advanced Disease T1bN1-T4a Any N PreOp CCRT Surgery Def CCRT(Only for patients who decline surgery) .

32. Locally advanced Disease Pre Op CCRT Carbo/Taxol x weekly for 5 cycles + RT 41.4Gy/23Fx Carbo AUCx2 day 1 Taxol 50mg/m2 day 1 RESPONSE ASSESMENT PET CT SURGERY RESPONSE ASSESMENT OF CCRT ON SURGICAL SPECIMEN ADJUVANT RO/R1/R2- OBSERVATION ypT+N+🡪 Nivolumab .

33. FOLLOWUP FOR TRIMODALITY H & PE CTC/A q6monthly for 2 yrs .

34. Locally advanced Disease UNRESECTABLE –T4B DEF CCRT RT 50-50.4Gy/28Fx Carbo AUC 2+pacli 50mg/m2 weekly for 5 weeks🡪 Adeno Cisplatin 100mg/m2 Day 1 +5FU1000mg/m2 Day1-4 at week 1,5,8,11🡪 SCC 2 cycle with RT ,2 cycle without RT CHEMO ALONE Involvement of trachea,heart,great vessel Transtuzumab+chemo Transtuzumab 8mg/m2 D1C1 then 6mg/m2 D1-28 Day cycle Cisplatin 100mg/m2 Day 1 +5FU1000mg/m2 .

35. Cervical Esophagus Standard of care - Definitive CCRT Carbo/Taxol RT 50-50.4Gy/28Fx In some cases treated like Head n Neck Ca- Dose For pure cervical Ca Increased RT dose – at least 54 Gy Higher doses up to 60- 66Gy may be considered .

36. Followup for CCRT(Bimodality) Endoscopy Every 3 monthly for 2 years 6 monthly for 3 rd yr Then as clinically indicated CTC/A every 6 monthly for 2 years. .

37. Metastatic .

38. Metastatic/recurrent/locally advance unresectable for chemo alone Pts ECOG ≤ 2 Consider MSI /MMR,PDL1 & HER2(Adenocarcinoma) Chemotherapy If Her 2 +ve cis+5fu/capecitabine+transtuzumab- first line ( category 1) If Her 2 –ve Cis+5Fu/capecitabine +pembrolizumab(MSI-H.Dmmr,PDL1>10) Pts ECOG > 2 Best supportive care .

39. CONTRAINDICATIONS TO SURGERY Distant mets T4b Bulky multistation LN Med comorbidity .

40. CHEMOTHERAPY Regimen chosen in the context of PS,Comorbidities and toxicity profile . .

41. Metastatic .

42. RADIOTHERAPY .

43. RT Techniques .

44. EBRT TECHNIQUES PATIENT POSITIONING: CERVICAL ESOPHAGUS: Supine with arms by the side and thermoplastic mask MID AND LOWER THIRD: SUPINE if AP – PA portals are being planned with arms up IMMOBILISATION : Perspex cast Vertebral column should be as parallel to couch as possible. CT slices 3–5mm .

45. SIM: NPO ×3 hours. Supine, arms up if tumor below carina (arms down if tumor above carina), immobilization device, iso at carina; scan from the mandible through stomach and celiac axis. Consider oral contrast to delineate tumor and head and neck mask for cervical primaries. 4DCT for GEJ tumors to account for movement

46. EBRT - DOSES Pre-Op CCRT : 41.4 Gy- 50.4 Gy in 23-28 # at 1.8 Gy per Post Op CCRT : 45 Gy-50.4Gy Definitive : 50-50.4 Gy OARS: TD 5/5 Lung( Normal Lung 2 cm outside PTV, NOT more than 40Gy ) V 20 : 20Gy to 20% V 40 : 40Gy to <10% Spinal Cord: <45 Gy ( @ 2Gy/ Fx- 10cm length) Heart Mean <30 Gy V 30 < 30% (20% preferred) Bowel <45Gy Liver 30Gy to <20% Kidney 1/3 rd <18 Gy (Single Kidney) .

47. Final consensus on the delineation guidelines .

48. CTVp 1.0 cm radially + 3.0 cm cranio-caudally 2.0 cm distal 🡪lower oesophagus and GEJ Crop (muscles, bones, large vessels and OARs) CTVn 1.0 cm It includes the lymph nodes stations along the CTVp CTVtotal CTVp and CTVn Potential gaps <3cm always include iCTV Can include muscles, large vessels and OARs. 0.5cm margin if 4DCT not available. .

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50. cT3N1M0 SCC middle esophagus .

51. Lower esophagus .

52. GEJ T3N1 .

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54. SUPPORTIVE TREATMENT .

55. DYSPHAGIA GRADING : Grade 0: able to eat solids irrespective of bite size Grade1 : able to eat solids cut into small pieces Grade 2: able to swallow semi solid ( baby food consistency ) Grade 3 : unable to swallow liquid only Grade 4: unable to swallow liquid or saliva Stenting preferred if curative surgery is not in treatment plan Second option is jejunostomy for enteral feeding if curative surgery is in plan .

56. OBSTRUCTION COMPLETE ESOPHAGEAL OBSTRUCTION Endoscopic lumen restoration via simultaneous retrograde and antegrade endoscopy Jejunostomy EBRT/brachytherapy Dilatation Stenting MODERATE ESOPHAGEAL OBSTRUCTION ( EATING SEMI SOLID) .

57. Scenario Preferred Option Imminent obstruction Stent Life expectancy <3 mo Stent Life expectancy >3 mo RT (EBRT or brachytherapy) Proximal tumor RT (avoid stent near trachea) Recurrent dysphagia post-RT Stent Key Studies SEMS vs. RT: Stents provide faster relief but higher complications (Javed et al., Gastrointest Endosc 2012). Brachytherapy has better long-term dysphagia control (Rosenblatt et al., Int J Radiat Oncol 2010). Dutch SIREC Trial: Stents had more complications than brachytherapy (Homs et al., Gastroenterology 2004).

58. Scenario Preferred Option Imminent obstruction Stent Life expectancy <3 mo Stent Life expectancy >3 mo RT (EBRT or brachytherapy) Proximal tumor RT (avoid stent near trachea) Recurrent dysphagia post-RT Stent Key Studies SEMS vs. RT: Stents provide faster relief but higher complications (Javed et al., Gastrointest Endosc 2012). Brachytherapy has better long-term dysphagia control (Rosenblatt et al., Int J Radiat Oncol 2010). Dutch SIREC Trial: Stents had more complications than brachytherapy (Homs et al., Gastroenterology 2004).

59. BLEEDING Acute – Endoscopic Evaluation And Coagulation Chronic – EBRT VOMITING : rule out obstruction via endoscopy .

60. THANKYOU .