Chapter 53 Esophageal Cancer Flashcards
What percentage of esophageal cancer diagnosed are curable?
Less than 15%
What percentage of esophageal cancer diagnoses are presented with unresectable or metastatic disease?
approximately half of patients
Length of oesophagus
25 cm
Lining of esophagus
Stratified keratinized squamous epithelium, extending from the cricopharyngeus muscle at the level of the cricoid cartilage superiorly to the gastroesophageal junction inferiorly. The lower one-third (5 to 10 cm) of the esophagus may contain glandular elements.
What is Barrett’s esophagus?
Replacement of the stratified squamous epithelium with columnar epithelium is referred to as Barrett’s esophagus, often occurring in the lower one-third.
What is Z-line in esophagus?
Endoscopically visible junction of the squamous and glandular epithelium
Describe layers of esophageal wall
3 layers: mucosa, submucosa,muscularis propria mucosal layer epithelium(M1), lamina propria(M2), muscularis mucosae(M3) submucosal layer inner (SM1), middle (SM2), and outer (SM3) musclaris propria circular inner layer and longitudinal outer layer The adventitia (periesophageal connective tissue) lies directly on the muscularis propria No serosa is present, facilitating extraesophageal spread of disease.
Describe 4 regions of esophagus(AJCC)
cervical upper thoracic midthoracic lower thoracic
Extension of cervical esophagus
begins at the cricopharyngeus muscle (approx. C7 level or 15 cm from the incisors) extends to the thoracic inlet (approx. T3 level or at approx. 20 cm from the incisors, at the level of the suprasternal notch), and therefore lies within the neck
Extension of thoracic esophagus
extends from approx. level of T3 (beginning at about 20 cm) to T10 or T11
Extension of upper thoracic esophagus
superiorly by the thoracic inlet and inferiorly by the lower border of the azygos vein extending from approx. 20 to 25 cm
Extension of middle thoracic esophagus
extends from the lower border of the azygos vein to the inferior pulmonary veins extending from approx. 25 to 30 cm
Extension of lower thoracic esophagus
extends from the inferior pulmonary veins and to the stomach and is inclusive of the gastroesophageal junction, typically extending from approximately 30 to 40 cm.
Define GE junction
Endoscopically, defined as the point where the first gastric fold is encountered, although this may be a “theoretical” landmark. Location of the GE junction can be accurately defined histologically as the squamocolumnar junction.
Recent AJCC staging system, subsites staged as an adenocarcinoma of the esophagus vs stomach cancer
epicenter in the lower thoracic esophagus gastroesophageal junction within the proximal 5 cm of the stomach (i.e., cardia) and extending up to the GE junction or esophagus vs epicenter is >5 cm distal to the gastroesophageal junction or within 5 cm of the gastroesophageal junction but does not extend to the junction/esophagus
Useful landmarks in reference to endoscopy Carina GE junction
Carina ∼25 cm from the incisors GE junction ∼40 cm from the incisors
Siewert et al. tumor characterization involving GE junction according to location of tumor
Type I adenocarcinoma of the distal esophagus : located >1 cm up to 5 cm above GE junction (Z-line) Type II : within 1 cm cephalad to 2 cm caudad to the GE junction, it is classified as type II. Type III : >2 cm below the GE junction However, locally advanced/ bulky tumors can make it difficult to accurately distinguish where tumors originated in relationship to the GE junction
Lymphatic drainage of esophagus
1.Longitudinal interconnecting system of lymphatics. 2.Lymphatic network is primarily located within the submucosa; however channels are also present within the lamina propria, facilitating spread of even superficial cancers of the esophagus involving the mucosa. 3.Intramural lymphatics may traverse the muscularis propria, facilitating tumor spread to regional lymphatic channels and paraesophageal nodes. 4.Autopsy series have demonstrated a relatively high incidence of directly draining channels extending from the submucosa lymphatics into the thoracic duct facilitating systemic spread. 5.Lymph can travel the entire length of the esophagus before draining into lymph nodes and thus the entire esophagus is at potential risk for lymphatic involvement 6.Up to 8 cm or more of ‘normal’ tissue can exist between gross tumor and micrometastases “skip areas” secondary to this extensive lymphatic network. 7.As many as 71% of frozen tissue sections scored as margin negative by conventional histopathology show involvement by lymphatic micrometastases with immunohistochemistry. 8.Lymphatics of the esophagus drain into nodes that usually follow arteries, including the inferior thyroid artery, the bronchial and esophageal arteries, and the left gastric artery (celiac axis)
What percentage of esophageal carcinoma accounts for GI malignancy?
6%
Ratio M:F esophageal cancer
4:1
Which countries have highest incidence of Esophageal carcinoma?
Linxian, China, Russia, and the Caspian region of Iran
Major risk factors of esophageal cancer
1.Alcohol and Tobacco 2.Diets of scant amounts of fruits, vegetables, and animal products 3.Plummer-Vinson (Paterson-Kelly) syndrome characterized by iron-deficiency anemia and low riboflavin levels 4.Nitrate rich foods 5.Achalasia and tylosis 6.Barrett’s esophagus 7.Obesity
Amount of consumption of alcohol and tobacco leading to RR of 155:1 esophageal cancer
>30 g/day of tobacco along with 121 g/day of alcohol
Which cancers are at an increased risk with Plummer-Vinson (Paterson-Kelly) syndrome?
oral cavity hypopharyngeal esophageal cancer
What percentage of incidence of SCC is associated with Achalasia and tylosis(long duration 25 years)?
5%
Patients with tylosis (hyperkeratosis of the palms and soles and papilloma of the esophagus) have what percentage of a reported risk in developing esophageal cancer at a mean age of 45 years.
38%
Name some nitrate compounds and nitrate rich foods
1.nitrosamines, nitrosamides, and N-nitroso compounds 2.nitrate-rich foods include pickled vegetables, alcoholic bever-ages, cured meats, and fish
What is the cause of Barrett’s Oesophagus?
Severe and long-standing gastroesophageal reflux
Barrett’s Oesophagus has which-fold increased risk of having Adenocarcinoma?
44-fold
Smokers have what-fold increased risk of having Adenocarcinoma Oesophagus than non-smokers?
2-3 folds
How long does relative risk of esophageal adenocarcinoma persists in contrast to a significant decline in similar patients with squamous cell carcinoma?
3 decades
What fold risk of Oesophageal adenocarcinoma is related with Obesity? Why?
3-4 folds Due to increased risk of reflux
What percentage of middle-aged patient with Barrett’s esophagus has a risk of developing esophageal adenocarcinoma during his or her lifetime?
10-15%
Genetic abnormalities involved in the genesis of SCCA esophageal cancer
-p53 mutations -multiple allelic losses at 3p and 9q, with amplification of cyclin D1 and epidermal growth factor receptor(EGFR)
Genetic abnormalities involved in the genesis of Adenocarcinoma esophageal cancer
-overexpression of p53 -multiple allelic losses at 17p, 5q, and 13q -amplification and overexpression of EGFR and human epidermal growth factor receptor 2 (HER-2)
Squamous cell carcinoma is characterized by extensive local growth and proclivity to lymph node metastases. Because the esophagus has no covering serosa, direct invasion of contigu-ous structures may occur early. Lesions in the upper esopha-gus can impinge on or invade the recurrent laryngeal nerves, carotid arteries, and trachea. If extraesophageal extension occurs in the mediastinum, tracheoesophageal or broncho-esophageal fistula may occur. Tumors in the lower one-third of the esophagus can invade the aorta or pericardium, resulting in mediastinitis, massive hemorrhage, or empyema.
A
Incidence of lymph node metastases with depth of penetration in Oesophageal cancer
18% of patients with spread to the submucosa had lymph node involvement
Percentage of nodal involvement in T1/T2 oesophageal cancer
T1 - 14% to 21% T2 - 38% to 60% At autopsy, lymph node metastases are found in approximately 70% of patients Distant metastasis can occur at almost any site
Factors significantly associated with nodal metastasis in oesophageal cancer
T stage tumoral length degree of differentiation
Skip metastasis (distant lymph node metastases without regional lymph node metastasis) occurred, usually in oesophageal cancer patients with?
poorly differentiated, large and deeply invasive tumors.
Anderson LL, autopsy findings SCCA Oesophagus what are the sites of distant metastasis?
Any sites (Lymph nodes,Lung,Liver,Adrenals,Diaphragm,Bronchus,Pleura, Stomach,Bone,Kidneys,Trachea,Pericardium,Pancreas)
Lower esophageal and gastroesophageal junctional ade-nocarcinomas, what percentage of patients will have nodal metastases at presentation. Factors influencing such metastasis?
70% 1.tumoral depth of penetration 2.all T3 and T4 lesions
Pathologic resection data demonstrated rates of lymphatic involvement for lower esophageal and GE junctional tumors of T2, T3, and T4 tumors
45%, 85%, and 100%
Primary direction for lymphatic flow for the lower esophagus?
The primary direction is toward the abdomen Involvement of both mediastinal and abdominal lymph nodes is common
Classification by Siewert, nodal metastases according to oesophageal tumors type I/II/III
Type I - mediastinum and abdomen Type II - preferentially spreading inferiorly and less frequently into the mediastinum Type III- almost exclusively inferiorly, toward the celiac axis
Japanese Gastric Cancer Association Classification Describe tumor stratification of esophagogastric junction carcinoma undergoing primary resection by Erlangen
AEG Type I (distal esophagus) Type II (gastric cardia) Type III (subcardia)
Japanese Gastric Cancer Association Classification Describe incidence of nodal metastasis by T-stage in esophagogastric junction carcinoma undergoing primary resection by Erlangen
Overall incidence of LN mets : 71% T1 - 17% T2 - 78% T3 - 86% T4 - 90%
University of Pennsylvania Fox Chase Cancer Center Adenocarcinoma of the esophagus and GE junction treated with surgery alone Percentage of LRR rate?
77%
Contemporary randomized trials, Esophageal cancer local failure rates with surgery alone?
32% to 45%
Recent randomized trials of esophageal cancer using “definitive” chemoradiation local failure?
Approx 50%
Clinical features of Esophageal cancer
1.Dysphagia >90% 2.Odynophagia 50% 3.Weight loss 40% to 70% of patients report loss of >5% of total body weight 4.Vague chest pain 5.Hoarseness 6.Cough 7.Glossopharyngeal neuralgia 8.Hematemesis, hemoptysis, melena 9.Dyspnea, and persistent cough secondary to tra-cheoesophageal or bronchoesophageal fistula 10.Compression or invasion of the left recurrent laryngeal nerve or the phrenic nerves can cause dysphonia or hemidiaphragm paralysis 11.SVC syndrome and Horner’s syndrome 12.Pleural effusion and exsanguination resulting from aortic communication may also be seen 13.Abdominal and back pain may occur with celiac axis nodal involvement with lower esophageal tumors
When does symptoms of esophageal cancer start?
3 to 4 months before diagnosis
Which is the best tool to diagnose and define the extent of the esophageal lesion?
Endoscopy
Advantages of endoscopy in esophageal cancer
1.Biopsies and brushings of primary site and suspicious areas harboring satellites or submucosal spread 2.RT treatment planning - accurate endoscopic measurement and characterization of tumor and gastroesophageal junction in relation to the incisors 3.Panendoscopy of the oral cavity, pharynx, larynx, and tracheo-bronchial tree in patients with squamous cell carcinomas, given the high incidence of second tumors in the head and neck and upper airways
Indication of bronchoscopy in esophageal cancer
Proximal malignancies to evaluate for the presence of tracheal or carinal invasion, patients with tumors abutting these structures on CT
Indication of CT thorax and abdomen in esophageal cancer
Identify metastases to the liver, upper abdominal nodes, or adrenals
Limitations of diagnostic CT in esophageal cancer
1.CT may not adequately assess periesophageal lymph node involvement or accurately define the true extent of the primary tumor 2.Accurately determine resectability in only 65% to 85% of cases 3.Accurately predicts T stage in approx. 70% of cases and 4.Nodal involvement in only 50% to 70% of cases
What is the diagnostic modality of choice to accurately assess periesophageal and celiac lymph node involvement and transmural extent of disease?
EUS Endoscopic Ultrasound
What is the accuracy of EUS for T and N stage in esophageal cancer?
When matched to surgical pathology 85-90% for tumor invasion (T stage) 75-80% for lymph node metastases
Accuracy of endoscopic ultrasound following neoadjuvant therapy in esophageal cancer
27-48% for T staging 38-71% for N staging This is possibly due to the failure to discriminate tumor from postradiation inflammation and fibrosis
What are the surgical staging procedure for additional staging information in esophageal cancer?
Thoracoscopy Mediastinoscopy Laparoscopy
What is the indication of feeding tube in esophageal cancer?
Significant esophageal obstruction with inability to maintain weight
The addition of PET to standard staging studies such as CT can improve the accuracy of detecting stage III and stage IV disease by what percentage?
23% and 18%
What percentage of patients will PET detect distant metastatic disease who are considered to have local regional disease only by CT?
20%
Histologic subtypes of esophageal cancer
SCC and Adenocarcinoma 95% Pseudosarcoma Verrucous carcinoma Adenoacanthoma Adenocarcinoma with squamous cell metaplasia Adenoid cystic carcinoma Mucoepidermoid tumors(adenosquamous carcinoma) Small cell carcinoma Leiomyosarcoma Kaposi’s sarcoma Malignant melanoma Lymphoma
Define T-stage esophageal cancer
T1a mucosa(lamina propria, muscularis mucosa) T1b sub mucosa T2 muscularis propria T3 adventitia T4a Resectable tumor(pleura, pericardium, diaphragm) T4b Unresectable tumor(Arota, vertebral body, trachea)
Define N-stage esophageal cancer
N1 regional 1-2 nodal mets N2 regional 3-6 nodal mets N3 regional >= 7 nodal mets
Define Tis stage in esophageal cancer
High grade dysplasia
Stage IA SCCA esophagus Adenocarcinoma
T1 G1 T1 G1-2
Stage IB SCCA esophagus Adenocarcinoma
T1 G2-3 T2-3 G1 Lower anatomic location T1G3 T2 G1-2
Stage IIA SCCA esophagus Adenocarcinoma
T2-3 G1 Upper/Middle anatomic location T2-3 G2-3 Lower anatomic location T2G3
Stage IIB SCCA esophagus Adenocarcinoma
T2-3 G2-3 Upper/Middle anatomic location T1-2 N1 T3 T1-2N1
Stage IIIA SCCA esophagus Adenocarcinoma
T1-2 N2 T3N1 T4a T1-2N2 T3N1 T4a
Stage IIIB SCCA esophagus Adenocarcinoma
T3N2 T3N2
Stage IIIC SCCA esophagus Adenocarcinoma
T4a N1-2 T4b N3 T4aN1-2 T4b N3
Stage IV SCCA esophagus Adenocarcinoma
M1 M1
Tumoral length as prognostic factor in esophageal carcinoma 5 year survival rate in tumor lengths of 1, 2, 3,>3 cm
77%, 48%, 38%, 23%
Mayo Clinic, clinicopathologic factors that affected prognosis in esophageal cancer
T and N status tumor grade age >76 years extracapsular lymph node extension absence of chemotherapy or radiotherapy weight loss and low overall performance status Deep ulceration of the tumor sinus tract formation fistula formation
Intergroup study evaluating chemotherapy preceding and following esophagectomy, what was the outcome?
Disease free survival was similar with R1/R2 resection Disease free survival was long only with R0 resection
What percentage of esophageal cancer patient present with initial and advanced stage?
Initial stage 20%(localized to esophagus) Locally advanced/distant stage 80%
Techniques used in esophagectomy
- Transhiatal esophagectomy 2. Right thoracotomy with laparotomy with intrathoracic anastomosis (Ivor-Lewis esophagogastrectomy) 3. Right thoracotomy with laparotomy with cervical anastomosis (McKeown esophagogastrectomy) 4. Left thoracotomy 5. Radical esophagectomy via open or laparoscopic approaches
Transthoracic resection esophageal cancer, patients undergoing margin-negative resection had a 5-year survival rate of ?
29%
Which esophageal lesion can be exposed in Ivor-Lewis procedure?
mid-esophageal lesions
Which esophageal lesion can be exposed in left thoracotomy?
gastroesophageal junction
Which esophageal lesion can be exposed in transhiatal esophagectomy?
lower esophageal lesions direct visualization and dissection of varying mediastinal lymph nodes cannot be achieved
Randomized trial comparing transhiatal versus transthoracic approaches in patients with Adenocarcinoma. What was the outcome?
No significant survival advantage Perioperative mortality was also increased with the transthoracic approach
What is the most widely used reconstruction surgery after esophagectomy?
esophagogastrostomy - stomach as a conduit to replace the esophagus
What is the management of lesions in thoracic esophagus(lesions of the middle to lower one-third of the thoracic esophagus and gastroesophageal junction)?
Subtotal or total esophagectomy Patients with stage I to III are often considered for potentially curative resection; however, aortic, tracheal, heart, or great vessel invasion may preclude resection.
What is the management of SCCA cervical esophagus?
Proximal esophageal tumors <5 cm from the cricopharyngeus are generally treated with definitive chemoradiotherapy.
Management of SCCA cervical esophagus ChemoRad vs Surgery?
Extensive surgery with radical neck dis-section needed. ChemoRad- survival probability is similar, without the major functional impairments, morbidity, and mortality associated with surgery.
What are the palliative treatment modalities of esophageal cancer with dysphagia as palliative symptom?
Surgical palliation Endoscopic dilation Palliative irradiation
Describe endoscopic dilatation as palliative treatment modality of dysphagia in esophageal cancer?
When the lumen of the esophagus is dilated to 15 mm, dysphagia is often no longer experienced. Repeat dilatation is often required. Esophageal stenting with either conventional plastic stents or metallic self-expanding stents can also be used to maintain patency
Describe palliative irradiation treatment modality of dysphagia in esophageal cancer?
Resolution of symptoms 80% Palliative treatment regimens -30 Gy over 2 weeks to 50 Gy over 5 weeks Laser ablation with or without intraluminal brachytherapy -7 Gy x 3 fnx improve the stenosis free interval and prevent obstruction
Describe treatment simulation in esophageal cancer
CT 3-5mm cut Palpable node marked with radio opaque wire Oral contrast Arterial phase intravenous contrast is generally used to delineate mediastinal and abdominal vas-cular nodal basin 4D CT, Resp gating or Breath hold tech. for target motion Repeat CT planning if patients lose >10% of their body weight during therapy
Define GTV in esophageal cancer
GTV is based on multiple studies: -EGD and EUS -The proximal and distal aspects of the tumor should be based on distance from the incisors, as well as relationship to varying landmarks as mea-sured from the incisors (e.g., the GE junction)
Fox Chase Cancer Center, what was the finding of PET/CT correlation with endoscopic findings in terms of mean GTV esophageal cancer?
Closely correlates PET/CT and endoscopic findings
SUV value of esophageal gross tumor in PET
>2 - 2.5
Prospective study Proximal and distal margin on primary tumor with percentage of coverage?
Squamous cell carcinoma 3-cm margin proximal/distal cover microscopic disease extension in 94% GE junctional carcinomas 3-cm proximal margin cover 100% and 5 cm distally covered 94% of subclinical spread
Describe field design for esophageal cancer Conventional field design
Upper cervical or postcricoid lesion -Laryngopharynx to the carina -Supraclavicular and superior mediastinal nodes are irradiated electively -Lateral parallel opposed or oblique portals and single anterior field for the supraclavicular and superior mediastinal nodes are irradiated electively Four-field box approach -wax bolus to build up the lack of tissue above the shoulders, acting as a compensator -high-energy beam (>15 MV) is used, and both sides of the neck are treated prophylactically. lesions at the thoracic inlet -140-degree arc rotations, anterior wedged pairs, and three- or four-field techniques using posterior oblique portals combined with a single anterior portal or anteroposterior–posteroanterior (AP/PA) fields 3D technique -primary tumor and lymph nodes -AP/PA approach to 39.6-41.4 Gy at 1.8 Gy per fraction, followed by a left or right opposed oblique pair to bring the total dose to 50.4 Gy, thereby limiting the spinal cord dose. -separate electron field is often added, treating to a depth of 2 to 3 cm, depending upon individual anatomy IMRT - preferred method
Nodal basin for cervical and upper thoracic SCCA esophagus
Superior -lower cervical and supraclavicular region Inferior -subcarinal lymph node basin, inclusive of the upper paraesophageal lymph nodes
Nodal basin for lower esophageal SCCA
Superior -subcarinal region Inferior -left gastric and common hepatic artery/celiac lymph
Nodal basins for middle esophageal cancer
paraesophageal mediastinal lymph nodes, particularly in patients with a good performance status
What is the sensitivity of FGD PET and EUS in detecting nodal metastasis in esophageal cancer?
FGD PET 67% EUS 75%
Describe the design of radiation field for the treatment of adenocarcinoma of the esophagus?
similar to that of lower thoracic squamous cell carcinomas
Involvement of lymph node in esophageal carcinoma is associated with ?
depth of tumor penetration (T stage)
Proximal extension of tumors (particularly beyond the Z-line into the distal esophagus for type II and III tumors) predicts an increasing incidence of which nodal involvement?
paraesophageal lymph node involvement
What nodal basins should be included in the CTV based on estimated nodal incidence cutoff of 20% in esophageal cancer?
lower paraesophageal, paracardial, lesser curvature, and left gastric artery nodes
Presence of lymph vascular invasion predicts a nodal positivity rate of >20% in which group of lymph nodes in esophageal cancer?
the left and right gastroepiploic, greater curvature, celiac trunk, and splenic hilar regions
In T3/4 disease, which group of lymph nodes should be included in esophageal cancer?
the gastroepiploic, greater curvature, celiac trunk, splenic hilar, splenic artery, and common hepatic artery
In high grade tumors, which group of lymph nodes should be included in esophageal cancer?
left gastroepiploic, greater curvature, and celiac trunk nodes should also be included
+
the gastroepiploic, greater curvature, celiac trunk, splenic hilar, splenic artery, and common hepatic artery
What group of lymph nodes should also be included in larger and more deeply penetrating tumors in esophageal cancer?
splenic artery and splenic hilar nodes, nodes along the greater curvature
+
left gastroepiploic, greater curvature, and celiac trunk nodes should also be included
+
the gastroepiploic, greater curvature, celiac trunk, splenic hilar, splenic artery, and common hepatic artery
Tumors extending above the diaphragm and those extending >1.5 cm beyond the Z-line, what group of lymph nodes should be included?
mid paraesophageal nodes, treating up to the carina.
How will you treat significant involvement of the distal esophagus by GE junctional tumors (>1.5 cm beyond the Z-line)?
inclusion of not only lower, but also middle paraesophageal nodes based on patterns of spread
treating these more extensive fields must be weighed against potential side effects of increased normal-tissue irradiation
what group of patient with esophageal cancer should treat middle and lower paraesophageal nodes?
T2-T4 type I
T2-T4 type II tumors extending >1.5 cm above the Z-line and T3-T4 type II patients.
Describe Potential beam orientations for the treatment of thoracic esophageal and gastroesophageal junction tumors.
- epicenter within 5 cm proximal or distal to the GE junction
- AP/PA-alone approach
- Initial AP/PA approach followed by AP/right posterior oblique (RPO)/left posterior oblique (LPO) fields with or without boost
- Initial APPA approach followed by RAO/LPO fields with or without boost
- 3-field technique (AP/PA with left lateral or oblique field). -One of our preferred approaches in lesions of the thoracic esophagus or GE junction is to use an initial AP/ PA/RAO/LPO fields, with boost fields using laterally oriented beams.
- The inferior margin of the initial fields includes the gastroesophageal junction and, for lower or middle one-third lesions, the celiac axis nodal basins (generally located at the level of T12 and identifiable on CT), as well as gastrohepatic ligament.
Initial fields are treated to a dose of 45 Gy, taking care to avoid as much of the heart as reasonably possible while continuing to minimize the kidney volume in the radia- tion field, inclusive of the above nodal basins.
Reduced fields encompassing gross disease with an approximate 2-cm margin through oblique or lateral fields may then be used for an additional 5.4 Gy. Doses usually do not exceed 50 Gy
Describe margin recommended to cover subclinical submucosal/nodal disease
5 cm above and below the GTV
approximate 2.0- to 2.5-cm radial margin, although individual margins are case dependent.
additional margin must be added to a clinical target volume, particularly to the more mobile distal esophagus to account for daily setup uncertainty as well as physiologic internal organ motion (secondary to respiration,peristalsis, cardiac motion, etc.).
ITV has been used to account for physiologic motion of the target volume, which is included in the PTV.
Describe reports analyzing esophageal motion
average AP motion ranges from 0.1 to 4 mm
lateral motion from 0.3 to 4.2 mm
superior-to-inferior motion from 3.7 to 10 mm.
interfraction esophageal motion
average right–left motion of 1.8 ± 5.1 mm (favoring leftward movement)
average AP motion of 0.6 ± 4.8 mm (favoring posterior movement)
average absolute motion of 4.2 mm or less in the right–left and AP directions.
authors concluded that 12-mm left, 10-mm posterior, and 9-mm anterior margins are appropriate.
Some authors have recom- mended defining 1-cm radial, 1.5-cm distal, and 1-cm proxi- mal margins from CTV to ITV if target motion data are not available.
Image-guided radiation therapy, including cone beam CT, may also be useful in localizing tumor and establishing physiologic variability between daily treatments.
what are the potential disadvantages of IMRT in esophageal cancer planning?
-the possibility of delivering low doses of radiation therapy to nor- mal tissue areas that might not normally be irradiated using 2D or 3D techniques.
possible dose inhomogeneity, leading to potential hot spots in normal organs
Dose constraint for spinal cord
45 Gy using 1.8-Gy fractions
Dose constraint for heart
off-heart approach using oblique orientations (including right anterior and left posterior
one-third, two-thirds, and total heart volumes of <45, 40, and 30 Gy, respectively. Recommended heart constraints include keeping <30% of the cardiac volume to a total dose of 40 Gy and <50% receiving 25 Gy, minimizing dose to the left ventri- cle. In the setting of potentially significant volumes of heart in the radiation field, consideration of 4D CT and/or breath-hold techniques can be made.
Dose constraint for lung
lung V20 of <20%, limiting >2,300 cc of normal lung tissue to <5 Gy, and using mean lung dose of <18 Gy. Similarly, a V10 of ≤60% has been proposed to reduce the incidence of postoperative pulmonary complications
volume of irradiated lung can be minimized using a simple AP/PA approach. However, this sometimes results in significant cardiac dose, particularly in lower esophagus and gastroesophageal junction tumors. Therefore, oblique orientations are sometimes used, resulting in increased volumes of normal lung being irradiated. When giving concurrent chemotherapy, we generally limit these fields to 13 to 15 Gy.
Dose constraint for kidney
For lower esophageal and gastro- esophageal cancers, it is recommended that at least 70% of one physiologically functioning kidney receive a total dose of <20 Gy, and that, collectively, no more than 50% of the com- bined functional renal volume should receive >20 Gy
Dose constraint for liver
70% of the liver paren- chyma should be kept to a dose of <30 Gy. Many of these con- straints can be achieved through the use of three-dimensional planning with appropriate and careful design of shielding blocks/multileaf collimation and dose-volume histogram analy- sis, with the use of IMRT in select cases
Minsky et al.
randomized trial,236 patients with clinical stage T1-4, N0/1, M0 squamous cell or adenocarcinoma of the esophagus were selected for nonsurgical therapy.
cervical, mid, or distal esophageal cancer were eligible, with the exception of those with tumors within 2 cm of the gastroesophageal junction, with approximately 85% of patients with squamous cell histology.
What was the randomized dose?
What was the conclusion of the study?
64.8 versus 50.4 Gy, both with concurrent 5-fluorouracil and cisplatin chemotherapy
interim analysis showed no probability of superiority in the high-dose arm.
median survival (13 vs. 18.1 months)
2-year survival (31% vs. 40%)
local- regional failure/persistence of disease (56% vs. 52%)
Based on these data, standard dose of radiation therapy for esophageal cancer is usually 50 to 50.4 Gy at 1.8 to 2 Gy per fraction, including delivery of similar doses in the both the definitive, adjuvant (45 to 50 Gy) or neoadjuvant (45 to 50 Gy) settings.
Dose prescription in Brachytherapy Esophagus
Doses of 5 to 20 Gy are usually delivered to a depth of 1 cm from the center of the catheter
Review of the Princess Margaret Hospital data, What is the most important factor influencing survival
significant correlation between T stage and response to treatment:
T1 lesions 100% response rate
T2 and T3 lesions 68% and 58%, respectively.
20% of patients with stage I disease were alive at 3.5 years
11% of stage II patients were alive after the same interval
all patients with stage III died of disease by approximately 1.5 years following therapy.
A trial from the Netherlands randomized 220 patients with esophageal adenocarcinoma to transhiatal esophagectomy alone or transthoracic esophagectomy with extended lymph node dissection.
Describe the outcome and conclusion
Transhiatal resection
- significantly fewer pulmonary complications and chylous leaks
- significantly reduced ventilator dependence and intensive care unit and hospital stays.
At a median 4.7-year follow-up, no significant difference in local-regional recurrence was seen between the two groups (32% transhiatal vs. 31% transthoracic)
No significant differences were seen in median disease-free survival (1.4 vs. 1.7 years; p = .15) or median overall survival (1.8 vs. 2.0 years; p = .38)
The authors concluded that a transhiatal approach was associated with less morbidity relative to transthoracic surgery, with no apparent survival advantage with either technique, although a trend toward improved survival with longer follow-up was seen.
In summary, none of the surgical approaches to localized esophageal cancer has clearly been shown to be superior with regard to complications or outcomes, and no one standard surgical approach exists for esophageal cancer resection.
Prospective, randomized trials using surgery alone in the treatment of esophageal cancer have reported 3-year survival rates
6% to 48% with more favorable rates likely reflecting inclusion of patients with earlier-stage disease
When Radiation therapy alone has been usually delivered in Esophageal cancer?
lesions are deemed inoperable because of tumor extent
medical contraindications
palliative treatment
Patients receiving radiation as a sole treatment modality have a median survival of
6 to 12 months
5-year survival of <10%
A large review analyzing 49 series involving >8,400 patients treated primarily with radiation therapy alone found overall survival rates
1, 2, and 5 years to be 18%, 8%, and 6%, respectively.
Hancock and Glatstein reviewed 9,511 patients
5 years survival rate
found only 5.8% were alive at 5 years.
Okawa et al. reported 5-year survival rates by stage.
stage I disease 20%
stage II 10%
stage III, 3%
stage IV, 0%
Overall, the 5-year survival rate was 9%.
For cervical esophageal lesions treated with radiation alone, the cure rates are comparable with those in patients treated with surgery alone.
Lederman treated 263 patients with radiation therapy alone and reported 3- and 5-year survival rates
11% and 7%, respectively
In a more contemporary series, an Intergroup randomized study comparing combined chemotherapy with 5-FU and cisplatin with radiotherapy (50 Gy) versus radiotherapy only (64 Gy) showed that 3-year survival with radiotherapy alone
0%
These and other data suggest that treatment with radiation therapy alone for esophageal cancer patients is palliative in the vast majority of patients.
Comparison of surgical studies in randomized trials
Use of preoperative radiation therapy in Esoohageal cancer
increased resectability of tumors
increased tumor radioresponsiveness secondary to improved tumor oxygenation
a theoretical decreased likelihood of dissemination at the time of surgery
avoidance of surgery in patients with rapidly progressive disease.
historical randomized studies comparing preoperative irradiation followed by surgery with surgery alone. These studies demonstrate no clinical benefit to the use of preoperative radiation therapy alone
Launois et al. Esophageal cancer reported delivering 40 Gy over 8 to 12 days with surgery 8 days later versus surgery alone. What was the outcome?
Resection rates were similar—70% and 58% for preoperative irradiation and for surgery alone, respectively.
The 5-year survival rate after resection was 11.5% with surgery alone, compared with 9.5% with irradiation and surgery.
European Organisation for Research and Treatment of Cancer (EORTC), used 33 Gy over 12 days, preoperative irradiation vs surgery alone Esophageal cancer. what was the outcome?
There was no significant difference in survival
Arnott et al. reported on 176 patients, 86 of whom were treated with esophagectomy alone versus 90 who were treated with preoperative radiation therapy. Preoperative radiation therapy was delivered with 4-MV photons using opposed fields, delivering 20 Gy at 2 Gy per fraction. Resectability and local failure were not reported. What was the outcome?
Patients receiving low-dose radiation therapy did not demonstrate a benefit in 5-year overall survival rates (17% vs. 9% for surgery and preoperative radiation, respectively; p = .4).
Wang et al. Esophageal cancer randomized 206 patients to surgery alone versus 40 Gy in 2-Gy fractions delivered preoperatively. what was the outcome?
No significant survival advantage was seen for patients receiving radiation therapy (35% vs. 30%; p > .05).
A meta-analysis from the Oeosophageal Cancer Collaborative Group updated data from five randomized trials of >1,100 patients comparing preoperative radiotherapy alone versus surgery alone. The majority of patients had squamous cell carcinoma. At a median follow-up of 9 years, what was the outcome?
HR 0.89, suggestive of an overall reduction in the risk of death of 11% and absolute survival benefit of 4% at 5 years with the use of preoperative radiotherapy. However, this was not statistically significant (p = .06).
The authors concluded that there was no clear evidence that preoperative radiotherapy improves survival of patients with potentially resectable esophageal cancer.
French trial, 221 patients with squamous cell carcinoma of the mid-lower esophagus undergoing esophagectomy were randomized to postoperative radiation therapy or no further treatment. Patients were stratified by extent of nodal involvement.
Total dose was 45 to 55 Gy at 1.8 Gy per fraction
beginning within 3 months of surgery.
What was the outcome?
Five-year survival in node-negative patients was 38% versus 7% with involved nodes.
No significant survival difference was seen in patients receiving postoperative radiation versus surgery alone.
radiation therapy did not improve survival after resection for squamous cell carcinoma
University of Hong Kong
randomized trial of 130 patients treated with post- operative radiation therapy versus surgery alone.
Patients who underwent either curative or palliative resections were included in this trial.
Radiation therapy was delivered to a total dose of 49 Gy (curative patients) or 52.5 Gy (palliative patients) using 3.5-Gy fractions.
Most patients had squamous cell histology.
What was the outcome?
Local recurrence 15% of patients receiving radiation and 31% of patients with surgery only (p = .06).
squamous cell carcinoma, the local recurrence rate was 15% with radiation therapy versus 36% with surgery alone (p = .02).
Median survival in patients was worse in patients receiving postoperative radiotherapy versus control patients (8.7 vs. 15.2 months; p = .02).
Ten patients undergoing surgery alone had tracheal bronchial recurrence resulting in death versus 3 patients receiving adjuvant radiation therapy (p = .07).
The authors concluded that postoperative radiation therapy was associated with increased morbidity and death caused by irradiation injury, as well as with the early appearance of metastatic disease and a reduced overall survival, although patients receiving radiation therapy were less likely to have a tracheobronchial recurrence. However, it should be noted the high rate of complications associated with radiation therapy in this study may possibly be related to the high dose per fraction and large total dose delivered.
Xiao et al.
randomized 549 patients to radical resection versus radical resection followed by radiation therapy.
All patients had squamous cell carcinoma.
The radiation dose delivered was 60 Gy in 6 weeks. Patients were classified into three groups:
group 1, no lymph node involvement;
group 2, one to two lymph nodes involved;
group 3, three or more lymph nodes involved.
What was the outcome?
Results showed T stage, stage group, and the number of lymph nodes involved by tumor were highly predictive of survival.
The 5-year survival for groups 1, 2, and 3 were 58.1%, 30.6%, and 14.4%, respectively.
Local control and survival were improved in patients receiving postoperative irradiation.
For patients with involved lymph nodes, 5-year survival for resection-only patients versus patients receiving resection and radiation therapy were 17.6% and 34.1%, respectively (p = .04).
French trial, University of Hongkong report, Xiao et al.
SCCA Esophageal cancer
what was the conclusion of trials?
In summary, postoperative radiation therapy may decrease local recurrence, particularly in the setting of involved mar- gins, although the impact of this adjuvant treatment on overall survival remains less clear.
