# Radiation Oncology/Esophagus/Overview

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Esophageal Cancer Overview

## Epidemiology

* Esophageal Cancer
* 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) PMID 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: PMID 11525305, PMID 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 PMID 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) PMID 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