Radiation Oncology/Esophagus/Overview

Esophageal Cancer Overview Epidemiology Incidence: 15,600 cases in US (2007 Estimate) Incidence rate about 200-260 per 100,000 Higher incidence in men 4x (12.1k vs. 3.4k) Higher incidence in African Americans by 5x Deaths: 13,900 deaths in US (2007 Estimate) Percentage and overall incidence of adenocarcinomas is increasing; increasing number of cancers involving the distal esophagus. 1/3 of H&N cancer patients who develop a second primary tumor will have esophageal cancer. Barrett's esophagus risk for developing adenoCa is significantly higher (14-150x) over general population, and corresponds ~0.5% per year. Progression is more likely with development of dysplasia within the metaplastic area, occurring in ~20% patients Leeds; 2007 (UK) 17890521 -- "Risk of Mortality and Cancer Incidence in Barrett's Esophagus." (Cook MB, Cancer Epidemiol Biomarkers Prev. 2007 Oct;16(10):2090-6. Epub 2007 Sep 21.) Retrospective. 502 patients with BE. Standardized mortality ratios (SMR) and standardized incidence rates (SIR) estimated Outcome: Overall mortality elevated (SMR 1.21), even after excluding esophageal CA (1.16). Risk for esophageal CA mortality (SMR 7.3), digestive tract diseases (SMR 2.0) Esophageal CA incidence rates: overall esophageal CA SIR 8.7, esophageal adenoCA 14.3 Conclusion: Increased risk of esophageal CA incidence (9x; for adeno 14x) and mortality (7x) Risk Factors Tobacco Alcohol Fruits and vegetables - protective Socioeconomic status - low is worse, particularly in African American men Obesity - worse for adeno GERD - associated with development of Barrett's H. pylori - protective for adeno Barrett's esophagus - single most important risk factor for adeno Tylosis - autosomal dominant, tylosis esophageal cancer (TOC) gene, develop esophageal papillomas, and at extremely high risk of developing esophageal cancer Plummer-Vinson - approximately 10% develop hypopharynx or esophagus cancer Caustic injury Achalasia Prior aerodigestive tract malignancy Anatomy Length is about 25 cm. Esophageal lesion distance on EGD is typically given from incisors Clinically important distance is from incisors to GEJ, which is ~40 cm. Layers: Mucosa: epithelium, lamina propria, muscularis mucosa. Separated by basement membrane from rest of esophageal wall Submucosa: fibroelastic fibers, nervous plexuses, glands Muscularis propria: inner circular muscle layer, outer longitudinal muscle layer Adventitia: dense periesophageal connective tissue The serosa only lines the intra-abdominal esophagus AJCC divisions of the esophagus: (These are based on adjacent surgical landmarks) Cervical esophagus: Hypopharynx to the thoracic inlet, which is at the level of the sternal notch. By endoscopy, 15 to <20 cm from the incisors If thickening of the esophageal wall begins above the sternal notch, the location is cervical Upper thoracic esophagus: Thoracic inlet to lower border of the azygos vein By endoscopy, 20 to <25 cm Middle thoracic esophagus: Lower border of the azygos vein to the inferior pulmonary veins By endoscopy, 25 to <30 cm Lower thoracic esophagus and EG junction: Inferior pulmonary veins to the stomach; includes the intraabdominal portion of the esophagus By endoscopy, 30 to 40 cm For cancers arising near the EGJ, they are staged as esophageal/EGJ if the epicenter is in the lower thoracic esophagus, the EGJ, or within the proximal 5 cm of the stomach (cardia) and extend into the EGJ or esophagus Those with an epicenter in the stomach greater than 5 cm distal the EGJ, or those within 5 cm of the EGJ but that do not extend into the EGJ or esophagus, are staged as gastric Siewert classifaction is disregarded Historical divisions of the esophagus Cervical esophagus - begins at cricopharyngeal muscle, 18 cm from the incisors (C7 level), to the thoracic inlet, 20-24 cm from incisors (T3 level). Thoracic esophagus - from thoracic inlet, 24 cm from incisors (T3), to GE junction (usually T10 or T11). Upper thoracic - T3 to T4, 20 cm to 25 cm - thoracic inlet to carina Mid thoracic - T5 to T8, 25 cm to 35 cm - carina to inferior pulmonary vein Lower thoracic - T9 to T10, 35 to 40 cm - below pulmonary vein GE junction: (Classification by Siewert: 11525305, 9823902), center within 5 cm proximal/distal to GEJ Type I (distal esophagus) - arises from area with specialized intestinal metaplasia of the esophagus. Commonly, center of the tumor located 1 - 5 cm above the gastroesophageal junction Type II (cardia, considered gastric) - arises from the cardiac epithelium or short segments with intestinal metaplasia at the GEJ. Commonly, center of the tumor located 1 cm above to 2 cm distal to GEJ Type III (sub-cardia, considered gastric) - arises from subcardial location and infiltrates GEJ from below. Commonly, center of tumor >2 cm distal to GEJ Resectability often limited: Lack of fibrous serosa to prevent local spread Rich lymphatic network in submucosa and muscularis that allows longitudinal and circumferential drainage Frequent medical comorbidities Barrett's Esophagus Multi-Institutional -- RFA vs. Sham procedure Randomized, 2:1. 127 patients, dysplastic Barrett's esophagus. Arm 1) RFA vs. Arm 2) Sham procedure. Primary outcome 1-year rate of dysplasia/metaplasia 2009 19474425 -- "Radiofrequency ablation in Barrett's esophagus with dysplasia." (Shaheen NJ, N Engl J Med. 2009 May 28;360(22):2277-88.) Outcome: In low grade dysplasia patients: complete eradication RFA 90% vs. sham 23% (SS). In high grade dysplasia patients 81% vs. 19% (SS). Disease progression RFA 4% vs. sham 16% (SS), cancer development 1% vs. 9% (SS) Toxicity: More chest pain, 1 patient UGI bleeding, 6% esophageal stricture Conclusion: RFA associated with a high rate of complete eradication of dysplasia and intestinal metaplasia, and reduced risk of disease progression Presentation 50% present with local or locoregional disease. Fewer than 60% of pts with locoregional disease are operable. Patterns of spread LN involvement risk is 20% for cervical tumors, 50% for mid thoracic, 30% for distal. Extensive longitudinal interconnecting system of lymphatics. LN+ risk by location: Cervical esophagus - 69% peritracheal & periesophageal. Only 6% supraclav, 9% abdominal LN. Upper thoracic - 29% superior mediastinal nodes, 27% middle mediastinal nodes, 29% lower mediastinal nodes, 32% abdominal nodes Middle thoracic - 11% superior mediastinal, 21% middle mediastinal, 18% lower mediastinal, 40% abdominal nodes Lower thoracic - 10% superior mediastinal, 14% middle mediastinal, 27% lower mediastinal, 70% abdominal nodes LN+ risk by stage T1a - 7% T1b - 20% T2 - 40% Overall distant metastasis rate 50%. Most commonly to the lung and liver. Southern Tohoku, Japan; 2009 (1989-2008) 19042946 -- "Determination of the irradiation field for clinical T1-T3N0M0 thoracic/abdominal esophageal cancer based on the postoperative pathological results." (Nakamura T, Jpn J Clin Oncol. 2009 Feb;39(2):86-91. Epub 2008 Nov 28.) Retrospective. 95 patients, clinical T1-T3N0 thoracic/abdominal esophageal cancer. Squamous cell 85%, adeno 9%. Rate of pathologic LN involvement evaluated Outcome: Positive LN 42% (upper 37%, middle 32%, lower 46%, abdominal 70%). Radiation fields: Extent of irradiation fields for each subsite determined Conclusion: Lymph node mets seen often in cT1-T3; optimal fields designed Prognosis No treatment: 6 month OS 20%, 5-year OS 0% Surgery alone: 5-year OS 20-25% Stage I: 5-year OS 80-90% Stage IIA (T2-T3 N0): 50% Stage IIB (T1-T2 N1): 20% Stage III (T3-T4 N1): 10-15% Stage IVa (M1a): 10% Palliation of dysphagia with surgery - 80%. External Links MCQs on Esophagus