Esophageal Cancers

Najam Uddin

FCPS-II (Radiotherapy) Resident

AEMC Karachi
Contents
 Overview and benign neoplasm
 Anatomy
 Incidence and prevalence
 Sign symtoms and diagnosis
 Surgical treatment
 Radiation treatment
 chemotherapy
Eso tumors:
 Malignant > common than benign.
 Unfortunately, esophageal cancer discovered late & overall
5 year prognosis is bad < 10%.
 Even for potentally resectable ca eso, 5 y survival is < 30%
Benign Neoplasms
 The most common is a gastrointestinal stromal tumour (GIST, another
name for leimymoma),usually asymptomatic but may cause bleeding or
dysphagia
 Uncommon, include fibrovascular polyps, leiomyomas, papillomas,
lipomas, neurofibromas, granular cell tumors.
 When large, can cause dysphagia or chest pain from obstruction or
stretch.
 Usually discovered incidentally.
LEIOMYOMA OF OESOPHAGUS
 Most common benign tumor of esophagus & small bowel but not common in
the colon
 Usually asymptomatic
 May produce dysphagia or hematemesis if large.
 Typically occurs in young males
 Found most often in distal third of esophagus.
 Usually solitary, but may be multiple (3%).
 Imaging findings:
 Smooth, sharply-marginated mass.
 Well-defined, intramural (wall) mass &may narrow the lumen.
 May have coarse calcifications (only calcifying esophageal tumor)
 Rarely ulcerates
LEIOMYOMA OF OESOPHAGUS: diagnosis

 Barium swallow.
 Endoscopy: smooth submucosal lesion.
Ca esophagus.
ETIOLOGY & PATHOGENESIS.
 Almost all are adenocarcinoma or squamous cancers.
 Small-cell cancer is a rare third type.
 Anatomy

 The esophagus is a fibromuscular tube,

approximately 25cm in length that transports food
from the pharynx to the stomach. It originates at
the inferior border of the cricoid cartilage, C6,
extending to the cardiac orifice of the stomach,
T11. Anatomically, the oesophagus can be divided
into two parts: thoracic and abdominal.
 Anatomical Location and Structure
 The abdominal part of oesophagus is approximately 2cm long – it
terminates by joining the cardiac orifice of the stomach at level of
T11.
Muscular layers

The oesophagus consists of an internal

circular and external longitudinal layer of muscle.
Furthermore, the external longitudinal layer is
comprised of different muscle types in each third of
the oesophagus:

•Superior third – voluntary striated muscle.

•Middle third – voluntary striated and smooth muscle.
•Inferior third – smooth muscle.

Food is transported through the oesophagus

by peristalsis – a rhythmic contractions of the
muscles, which propagates down the oesophagus.
Anatomical Relations
Oesophageal Sphincters
 Upper Oesophageal Sphincter
The upper sphincter is an anatomical, striated muscle sphincter
at the junction between the pharynx and oesophagus. It is
produced by the cricopharyngeus muscle. Normally, it is
constricted to prevent the entrance of air into the oesophagus.

Lower Oesophageal Sphincter

The lower oesophageal sphincter is a physiological sphincter
located in the gastro-oesophageal junction (junction
between the stomach and oesophagus). The gastro-oesophageal
junction is situated to the left of the T11 vertebra, and is
marked by the change from oesophageal to gastric mucosa.
 Vasculature

 Thoracic
The thoracic part of the oesophagus receives its arterial supply from
the branches of the thoracic aorta and the inferior thyroid
artery (a branch of the thyrocervical trunk).Venous drainage into
the systemic circulation occurs via branches of the azygous veins and
the inferior thyroid vein.

 Abdominal
The abdominal oesophagus is supplied by the left gastric artery(a
branch of the coeliac trunk) and left inferior phrenic artery. This part
of the oesophagus has a mixed venous drainage via two routes: To the
portal circulation via left gastric vein To the systemic circulation via
the azygous vein. These two routes form a porto-systemic
anastomosis, a connection between the portal and systemic venous
systems.
Incidence
 4% of GIT tumors
 Age >>>>> 45-60 years old.
 Sex >>>>> Male (5% of all carcinomas) except in cervical esophagus
may be more common in females.
 It has geographical distribution showing higher incidence in some
countries as China and Japan.
 Relatively common in Kurdistan.
 Should be considered in any case presenting with dysphagia
SCC.
 In West relatively rare (4 cases /100 000), in Iran, Iraq Africa , China,common
(200/100 000).
 Can arise in any part of the oesophagus from the post-cricoid region to the
cardia.
 Almost all tumours above the lower third of the oesophagus are squamous
cancers.
Adeno ca.
 Arises in the lower third of the oesophagus from Barrett's oesophagus or
from the cardia of the stomach.
 The incidence is increasing & now 5:100 000 in UK; possibly because of
the high prevalence of GERD/ Barrett's.
 Predisposing factor
 Chronic lrritation:
 Spicy food, smoking & spirits.
 Food contamination by fungi
 Nirosamine used in food preservation.
 Barrett's esophaqus which is lined by columnar epithelium in reflux )
adenocarcinoma.
 Achalasia of esophagus.
 Tylosis type A (characterized by hyperkeratosis of palm and sole, 100%
esophagus carcinoma at age of 40 years).
 Decrease beta carotene, selenium, vitamin E in diet.
 Plummer-vinson syndrome
 postcoroosive
 Scleroderma.
 Benign tumors: Papilloma or adenoma.
 Pathology
 Site
Upper 1/3: 20% Middle 1/3: 30% Lower1/3 : 50%
 Macroscopic
Proliferative. infiltrating. Ulcerative.
 Microscopic
• Squamous cell carcinoma (40% upper 2/3 "rare").
• Adenocarcinoma (60% lower 1/3): from;
 Lower 3 cm (lined by columnar epithelium)
 On top of Barrett's esophagus.
 Upward spread from gastric carcinoma
 Recently incidence of adenocarcinoma
• Anaplastic: the cells show malignant criteria
 Siewert Classification

Siewert tumor type should be assessed in all patients with

adenocarcinomas involving the esophagogastric junction (EGJ).
Siewert Type I: adenocarcinoma of the lower esophagus (often
associated with Barrett's esophagus) with the center located within1
cm to 5 cm above the anatomic EGJ.
Siewert Type II: true carcinoma of the cardia at the EGJ, with the
tumor center within 1 cm above and 2 cm below the EGJ.
Siewert Type III: subcardial carcinoma with the tumor center between
2 and 5 cm below EGJ, which infiltrates the EGJ and lower
esophagus from below.
• Siewert type III lesions are considered gastric cancers
 Spread

 Direct spread  Thoracic esophageal:

1. Spreads transversely then lonqitudinallv Trachea >> fistula
(extensive submucosal lymphatic spread, Aorta ) fatal hematemesis.
proximal line of resection should be '10 cm
proximal to the upper limit of the tumor). Left recurrent laryngeal nerve.
Lung.
2. Neighboring structures: . Thoracic vertebrae.
 Cervical esophaqus:  . Abdominal esophaqus:

Trachea >> fistula. Liver.

Recurrent laryngeal nerve ) vocal cord paralysis. Stomach.
Thyroid. Diaphragm.
 Lymphatic Spread (early)
. Cervical esophagus ) deep cervical LNs.
. Thoracic esophagus ) posterior mediastinal, tracheal &
tracheobronchial LNs
. Abdominal esophagus ) left gastric & celiac LNs.

 Blood Spread
. Rare & late.
. mainly to liver & Iungs.

 Tronscoelomic
in abdominal esophagus e.g. krukenburg tumour.
Clinical picture
 Symptoms Male > 50 years old with.
 Dysphagia : rapidly progressive to solids > fluids, but later the
patient cannot swallow his own saliva leading to continuous
driplling of saliva.
 Regurgitation (blood stained) leads to pulmonary symptoms.
 Excessive salivation.
 Loss of Appetite.
 Symptoms due to infiltration of adjacent structures e.g.
change of voice due to infiltration of RLN.
SYMPTOMS.
 The most common is progressive dysphagia over a several-month
period until only liquids can be taken.
 The obstruction does not occur until the cancer is far advanced.
 The dysphagia may be accompanied by a steady, boring pain, which
often signals mediastinal involvement & inoperability.
SYMPTOMS.
 Unexplained persistent chest pain should always be investigated by a
careful double-contrast Barium or endoscopy.

 More advanced; halitosis & weight loss.

 Coughing after drinking fluid may be caused either by nearly complete

esophageal lumen obstruction, with overspill into the larynx, or by the
development of a tracheoesophageal fistula.

 Hematemesis & Hoarseness from involvement of the recurrent laryngeal

nerve by tumor are unusual symptoms.
 Signs

 General>>>> Cachexia, dehydration & chest infection.

 Local>>>> Neck: for presence of lymph nodes or mass.
Abdominal for palpable hard nodular liver & ascites.
SIGNS:
 Weight loss.
 Nail bed clubbing can be seen with both benign & malignant tumors.
 Vricho’s node in left supracalvicular region.
 Early diagnosis affords the only chance for cure.
Complication
 Mediastinits: due to esophageal perforation.
 Fatal hematemesis: due to aortic invasion.
 Paralysis of diaphragm and vocal cords.
 Pulmonary complications: (pneumonia, lung abscess etc.) (cause
of death)
DIAGNOSIS: staging.
 Evaluation for local tumor spread, mediastinal nodal involvement & liver
metastases is essential for staging before a therapeutic decision is
reached by:
 Physical examination for lymphadenopathy
 Tests of liver enzymes
 Chest radiography.
 CT scan.
 For upper & mid-esophageal tumors, bronchoscopy is indicated to
evaluate for asymptomatic invasion of the tracheobronchial tree.
 Endoscopic ultrasound (EUS) is useful to detect the level of invasion &
presence of mediastinal lymph node abnormalities & is becoming the
favored test to determine if a lesion is resectable.
Investigation
 for-diagnosis:
 Esophagoscope "early endoscopy is the key for good result"
+ biopsy + cytology
 Barium swallow:
 Rat tail appearance: Narrow lumen at site of Lesion with
mild proximal dilatation due to short duration (unlike
achalasia)
 Shoulderings.
 lrregular filling defect in cauliflower mass.
 Prestaltic wave may be absent above the lesion due to
infiltration of the wall .
 for-staging,
- Endoluminal sonar: show extent of tumor(the most important
for local staging and assessing operability)
- Chest X-Ray: elevated copula of diaphragm due toaffection of
phrenic nerve, pleural effusion.
- U/S ) liver metastasis.
- CT scan.
- Bone Scan.
- Bronchoscope >>> before barium swallow
- indirect Laryngoscope ) invasion of recurrent laryngeal
nerve.
 For preoperative preparation
 CBC. anemia & leucocytosis in chest infection.
 LFTs: for metastasis.
 Serum electrolytes & serum protein
 - KFTs.
 Treatment
1. lnoperable Tumors ( 60% of the patients)
Siqns of lnoperabilitv:-
 Clinical:
 1. Distant secondary's.
 2. Enlarged LNs.
 3.Voice change )recurrent laryngeal nerve infiltration.
 Radiolosical
 1. Enlarged mediastinal LN s
 2. Diaphragmatic paralysis.
 3.Vertebral erosion.
 Bronchoscopy>>>> tracheal invasion
 Exploratory:
 1. Fixed tumor. 2. Aortic invasion. 3. Secondaries in liver.
 Curative treatment entails Tri-modality use (S+CCRT)
 Tis Tia and Tib No can be treated by ER ± Ablation or
Esophagectomy.
 Surgery possible: Preoperative CCRT followed by
surgery
 Surgery not possible but still can bear CCRT: definitive
CCRT followed by Surveillance or surgery (if become
resectable)
 Palliative patients
intubation
The idea is to insert a rigid tube through the stenosed segment to keep a
patent lumen.
The tube is inserted by :
o Gastrostomy (e.9. Celestin tube)
o Esophagoscopy (e.9. Souttar tube).
Laser photocoagulation
Dysphagia can be relieved by endoscopic laser therapy.
A core of tumor is vaporized, opening the lumen without perforating
the esophagus.
Treatment needs to be repeated every 6-8 weeks.
gastrotomy
Obsolete nowadays as the patient remains unable to swallow his saliva
aspiration pneumonia
 Preoperative Preparation
 Surgery:
1) Tumors below the carina (tracheal bifurcation):
lvor Lewis operation (2 phases) for middle 1/3 tumors.
1st phase: Laparotomy & mobilization of stomach.
2nd phase: Rt thoracotomy through the 5th intercostal space,
resection of the tumor, LNs and 1Ocm of the esophagus above the
tumor & GE anastomosis.

2) Tumors above the carina:

Mc Keown operation (3 phases)
1st phase: Laparotomy & mobilization of stomach.
2nd phase: Rt thoracotomy through the 5* intercostal space and
oesphageal mobilization.
3rd phase: Neck incision, the esophagus & stomach are delivered
to the neck where resection is done and anastomosis of the
stomach & cervical esophagus is carried out.
Surgical Treatment
3) Tumors below the diaphragm (1 phase) for lower
1/3 tumours
• Lt thracoabdominal incision, the stomach & lower
esophagus are removed with Roux-en-Y
esophagojujenostomy.
4) Nowadays many surgeons prefer to do:
TranshiataI totaI esophagectomy
Chemotherapy Can be effective with surgery
especially with squamous cell carcinoma
Barrett’s esophageal
 10% of cases of GERD.
 Metaplasia of the lower end of the esophageal mucosa into
columnar type.
 A precursor for ulcers, dysplasia, cancer in situ and
adenocarcinoma.
 Regular endoscopic monitoring with multiple biopsies is
essential
 Endoscopic mucosa resection (EMR) using photodynamic
therapy or argon beam coagulation may be used before
progression to cancer.
 The best line of TTT of it is large dose of PPls
Radiotherapy Planning for Esophageal
Cancers
Some Centre use
Cervical Esophagus =60 – 66 Gy
•Dose escalation has not shown improved survival in
definitive CRT for esophageal cancers (INT 0123)
 Radiation for Esophageal Cancers
 Post – Operative
◦ Rare; difficult to tolerate
◦ 45 Gy

 Palliative
◦ Dysphagia
◦ 30 – 35 Gy
 Treatment Planning
 Simulation
◦ Immobilization
 Vac Lok
◦ Isocenter set-up
 2D vs. 3D
 3D – Treatment planning CT
◦ Tattoos
 Daily Set-up
 Treatment Planning
2D Era – RTOG 8501
 RTOG 8501 compared CRT (50 Gy) to RT alone (64Gy)
 Mid/Lower Esophageal Cancers
◦ Initial Field was AP/PA to 30 Gy in CMT arm
◦ Extended from SCV region to GE junction
 Omitted SCV nodes in lower esophageal tumors
◦ Boost field was tumor + 5 cm sup/inf with a 3 field or opposed obliques
 Advantages
◦ AP/PA limited lung dose
◦ Replacing PA with oblique fields limited spinal cord dose
 Disadvantages
◦ For distal tumors, significant cardiac volume
◦ Entire extent of the esophagus treated
 Treatment Planning – 3D Era
 Target Delineation
◦ PET-CT fusion
◦ EUS findings
 Definitions
◦ GTV – Gross Tumor Volume ( Tumor + grossly enlarged LN)
◦ CTV – Clinical Target Volume – Includes microscopic disease
◦ PTV – Planning Target Volume – accounts for setup error and intra-fraction
motion
 Margins / Normal Tissue Tolerances
 Margins / PTV definitions
◦ Superior / Inferior – GTV + 5 cm
◦ Lateral – GTV + 2 cm
 Normal Tissue Tolerances – Organs @ Risk (OAR)
◦ Cord - max dose 45 -50 Gy
◦ Lung V 20 Gy - 20 -30%
◦ Liver V 30 Gy – 23- 30%
◦ Kidney
◦ Heart
 Radiation Toxicities
 Esophagitis
 Esophageal Stricture
 Radiation Pneumonitis
◦ V20 Gy < 20-40%;V30 Gy < 18%; Mean Lung Dose <20 Gy
 Post-operative Pulmonary complications
◦ MDACC study showed that the amount of Lung that is spared
from 5 Gy of radiation predictive
 Radiation Toxicities
 Pericarditis
 Cardiovascular disease
◦ V40 Gy < 30%
 Radiation Nephropathy
◦ Limit dose to atleast 2/3 of 1 Kidney
 Treatment Planning
 3D Treatment Planning (CT- based)
◦ Start AP/PA
 Treat to cord tolerance
 39.6 – 41.4 Gy
◦ Then off-cord
 2 field or 3 field
 AP/RAO/LAO for cervical/upper thoracic lesions
 AP/RPO/LPO for lower lesions
 RAO/LPO for distal esophagus lesions
 Treat to total 50.4 – 54 Gy
 Treatment Planning - Evaluation
 Dose Volume Histograms
◦ CT data allows to quantify dose received by tumor as well as
organs at risk
3D Planning
3D Planning
3D Planning
 Some Remarkable points about RT
• Systemic therapy regimens recommended for advanced esophageal and esophagogastric junction (EGJ)
adenocarcinoma, squamous cell carcinoma of the esophagus, and gastric adenocarcinoma may be used
interchangeably (except as indicated).

• Regimens should be chosen in the context of performance status (PS), comorbidities, and toxicity profile.

• For metastatic adenocarcinoma trastuzumab can be added to chemotherapy if tumor overexpresses HER2-neu.

• Two-drug cytotoxic regimens are preferred for patients with advanced disease because of lower toxicity. Three-drug
cytotoxic regimens should be reserved for medically fit patients with good PS and access to frequent toxicity evaluation.

• Infusional fluorouracil and capecitabine may be used interchangeably without compromising efficacy (except as
indicated). Infusional fluorouracil is preferred over bolus fluorouracil.

• Cisplatin and oxaliplatin may be used interchangeably depending on toxicity profile.

• Preoperative chemoradiation is the preferred approach for localized adenocarcinoma of the thoracic esophagus or EGJ.2
Perioperative chemotherapy is an alternative option.

• In the adjuvant setting, upon completion of chemotherapy or chemoradiation, patients should be monitored for any long-
term treatment related complications.
3D Planning - DVH
 IMRT
 Intensity Modulated Radiation Therapy
◦ Clinical Rationale
 Tumors arise from/within normal tissues
 Normal tissues often limit the radiation doses that can be safely prescribed and
delivered
 Organs at risk in close proximity may have limited radiation tolerance

◦ IMRT allows for the reduction of radiation dose delivered to normal tissue

◦ Ability to maintain a high dose to the tumor

 IMRT - Benefits
 Normal Tissue sparing
◦ Reduced late toxicities

 Dose escalation

 Dose painting
◦ Ability to increase dose to areas of higher tumor burden

 Re-irradiation
 IMRT - Basics
 Multiple static non-coplanar radiation fields
◦ Each field has a unique radiation intensity profile
◦ The fluency of radiation is altered during the delivery of the radiation field

 Multileaf collimator

 Planning CT scan (can be “fused” to an MRI or PET scan)

 The tumor/volumes and critical structures are drawn

 Prescription dose and dose constraints are programmed into the radiation-planning
software for generation of the radiation plan
 Requirements for IMRT
 LINAC

 Beam modulation device

◦ MLC (multi-leaf collimator)
◦ MlMiC (Peacock system)
◦ Compensators

 (Inverse) treatment planning software

 QA program
Chemotherapy regimes list and protocol