Carcinoma oesophagus

Carcinoma Esophagus

Presented By:
Dr. Vandana
Dept. of Radiation Oncology
CSMMU, Lucknow

Clinical Anatomy
„ Hollow muscular tube 25 cm in
length which spans from the
cricopharyngeus at the cricoid
cartilage to gastroesophageal
junction (Extends from C7-T10).

„ Has 4 constrictions-
ƒ At starting(cricophyrangeal
junction)
ƒ crossed by aortic arch(9’inch)
ƒ crossed by left bronchus(11’inch)
ƒ Pierces the diaphragm(15’inch)

„ Histologically 4 layers:
mucosa, submucosa, muscular &
fibrous layer.
FIGURE Anatomy of the esophagus

Contd…
Four regions of the esophagus:
„ Cervical = cricoid cartilage to
thoracic inlet (15–18 cm from
the incisor).
„ Upper thoracic = thoracic inlet
to tracheal bifurcation (18–24
cm).
„ Midthoracic = tracheal
bifurcation to just above the GE
junction (24–32 cm).
„ Lower thoracic = GE junction
(32–40 cm).
Figure Anatomy of the esophagus with
landmarks and recorded distance from the
incisors used to divide the esophagus into
topographic compartments. GE,
gastroesophageal.

Lymphatic Drainage
„ Rich mucosal and submucosal
lymphatic system.

„ The submucosal lymphatics may
extend long distances (proximal and
distal margins used for RTP have
traditionally been a minimum of 5
cm).

„ The submucosal plexus drains into the
regional lymph nodes in the cervical,
mediastinal, paraesophageal, left
gastric, and celiac axis regions

Figure Lymphatic drainage of the esophagus
with anatomically defined lymph node basins

Epidemiology
„ Esophageal cancer is the 7th leading cause of cancer deaths.

„ accounts for 1% of all malignancy & 6% of all GI malignancy.

„ Most common in China, Iran, South Africa, India and the former Soviet
Union.

„ The incidence rises steadily with age, reaching a peak in the 6th to 7th
decade of life.

„ Male : Female = 3.5 : 1

„ African-American males : White males = 5:1

Contd…

„ Worldwide SCC responsible for most of the cases.

„ Adenocarcinoma now accounts for over 50% of esophageal cancer
in the USA, due to association with GERD , Barretts’s esophagus &
obesity.

„ SCC usually occurs in the middle 3rd of the esophagus (the ratio of
upper : middle : lower is 15 : 50 : 35).

„ Adenocarcinoma is most common in the lower 3rd of the esophagus,
accounting for over 65% of cases.

Risk Factors : Squamous Cell Carcinoma

„ Smoking and alcohol (80% - 90%)
„ Dietary factors
ƒ N-nitroso compounds (animal carcinogens)
ƒ Pickled vegetables and other food-products
ƒ Toxin-producing fungi
ƒ Betel nut chewing
ƒ Ingestion of very hot foods and beverages (such as tea)

„ Underlying esophageal disease (such as achalasia and
caustic strictures, Tylosis)

„ Genetic abnormalities:
ƒ p53 mutation, loss of 3p and 9q alleli, amp. Cyclin D1 & amp.
EGFR

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.

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.

Fig. Barretts’s esophagus

Pattern of spread
„ No serosal covering, direct invasion of contiguous structures occurs early.

„ Commonly spread by lymphatics (70%)

„ Lymph node involvement increases with T stage.
ƒ T1 – 14 to 21%
ƒ T2 – 38 to 60%

„ 25% - 30% hematogenous metastases at time of presentation.

„ Most common site of metastases are
ƒ lung, liver, pleura, bone, kidney & adrenal gland

„ Median survival with distant metastases – 6 to 12 months

Pathological Classification

95%

Clinical Features
„ It is commonly associated with the
symptoms of dysphagia, wt. loss, pain,
anorexia, and vomiting

„ Symptoms often start 3 to 4 months
before diagnosis

„ Dysphagia - in more than 90% pt.
Odynophagia - in 50% of pt.

„ Wt. loss – more than 5 % of total body
wt. in 40 – 70% pt. associated with
worst prognosis.

Contd…
Complications:
„ Cachexia, Malnutrition, dehydration, anaemia,.
„ Aspiration pneumonia.
„ Distant metastasis.
„ Invasion of near by structures: e.g.
ƒ Recurrent laryngeal nerve → Hoarseness of voice
ƒ Trachea → Stridor & TOF→ cough, choking &
cyanosis
ƒ Perforation into the pleural cavity → Empyema
ƒ back pain in celiac axis node involvement

AJCC TNM classification

„ a: Includes nodes
previously labeled as
“M1a”
„ b : “M1a” designation is
no longer recognized in
the 7th edn. of the AJCC
system

Staging : Squamous cell carcinoma

Staging : Adenocarcinoma
Group T N M Grade
0 Tis (HGD) 1, X
IA T1 1-2, X
IB T1 3
N0
T2 1-2, X
IIA T2 3
IIB T3
T1-2 N1
M0
IIIA T1-2 N2
T3 N1
T4a N0
Any
IIIB T3 N2
IIIC T4a N1-2
T4b Any
Any N3
IV Any Any M1

Diagnostic Workup
„ Detailed history & Physical examination: Dysphagia,
odynophagia, hoarseness, wt. loss, use of tobacco, nitrosamines,
history of GERD. Examine for cervical or supraclavicular adenopathy.
„ Confirmation of diagnosis:
ƒ EGD: allow direct visualization and biopsy, measure proximal & distal distance of
tumor from incisor, presence of Barrett’s esophagus.

Early, superficial Circumferential ulceration Malignant stricture
cancer esophageal cancer of esophagus

„ Staging:
ƒ CT chest and abdomen: Essential for staging because it can identify extension
beyond the esophageal wall, enlarged lymph nodes and visceral metastases.

Figure Esophageal cancer with aortic invasion. An Figure Esophageal cancer with tracheal invasion. CT
arc (bent arrow) of the contact between the scan shows circumferential wall thickening of the
esophageal cancer (arrows) and the aorta proximal esophagus (arrowheads), which shows
(arrowheads) is more than 90 degrees, indicating irregular interface with the posterior wall of the trachea
aortic invasion. (arrows), indicating direct extension into the lumen

Endoscopic Ultrasonography
„ EUS:
ƒ assess the depth of penetration and LN involvement. Limited by the degree of
obstruction.
ƒ Compared with EUS, CT is not a reliable tool for evaluation of the extent of
tumor in the esophageal wall.

Fig. —55-year-old man with T2 esophageal tumor (m)
shown on endoscopic sonogram. Note alternating
hyperechoic and hypoechoic layers (arrowheads) of normal
esophageal wall as seen on sonography. Innermost layer is
hyperechoic and corresponds to superficial mucosa. Second
layer is hypoechoic and corresponds to deep mucosa and
muscularis mucosae. Third layer is again hyperechoic and
corresponds to submucosa and its interface with muscularis
propria. Fourth layer is hypoechoic and corresponds to
muscularis propria, and outer fifth layer is hyperechoic and
corresponds to adventitia.

PET Scan
„ most recently, proven to be valuable staging tool
„ can detect up to 15–20% of metastases not seen on CT and EUS
„ low accuracy in detecting local nodal disease compared to CT / EUS
„ Value in evaluating response to Chemo Therapy & Radio Therapy
„ addition of PET to CT can improve specificity and accuracy of non-
invasive staging

Figure Distant lymph node metastases of esophageal cancer detected by integrated CT PET. A, Integrated CT
PET demonstrates para-aortic lymph node metastases showing increased FDG uptake (arrowheads). B,
Corresponding CT image shows lymph nodes (arrowheads) measuring 5 to 8 mm in diameter. Based on size
criteria, these lymph nodes may be considered benign on CT scan

„ Barium swallow:
ƒ can delineate proximal and distal margins as well as TEF
ƒ Helpful for correlation with simulation film.
„ Bronchoscopy: rule-out fistula in midesophageal lesions.
„ Routine Investigations: CBC, chemistries, LFTs.

Cancer lower 1/3 Apple core appearance
Rat tail appearance Filling defect (ulcerative type)

Management depends upon:

„ Site of disease
„ Extent of disease involvement
„ Co-morbid conditions
„ Patient preference.

Surgery
„ Prerequisite for surgery
ƒ disease should be 5 cm beyond cricophyrangeus.

„ Surgery indications
ƒ Lower 1/3 rd oesophageal ds involving GE junction.
ƒ Tumor size <5 cm .
ƒ palliative surgery

„ 5-Year OS for surgery alone is 20–25% (no significant difference
between surgical techniques according to results of 2 meta-analyses)
„ Local failure rate around 19–57% when used alone

„ surgical morbidity/mortality related to experience of the surgeons.

Types of Surgery
„ Transhiatal esophagectomy: for tumors anywhere in esophagus or
gastric cardia. No thoracotomy. Blunt dissection of the thoracic esophagus.
Left with cervical anastomosis. Limitations are lack of exposure of
midesophagus and direct visualization and dissection of the subcarinal LN
cannot be performed.

„ Right thoracotomy (Ivor-Lewis procedure): good for exposure of mid
to upper esophageal lesions. Left with thoracic or cervical anastomosis.

„ Left thoracotomy: appropriate for lower third of esophagus and gastric
cardia. Left with low-to-midthoracic anastomosis.

„ Radical (en block) resection: for tumor anywhere in esophagus or
gastric cardia. Left with cervical or thoracic anastomosis. Benefit is more
extensive lymphadenectomy and potentially better survival, but increased
operative risk.

Chemotherapy
„ No data proving that chemotherapy alone provides improved
survival or palliation. Partial response, not long-term remission, is
the rule

„ Indication
ƒ Used in combination with radiation for locally advanced cancers
ƒ Used as single treatment modality in stage IV disease
ƒ Combination chemotherapy has been used preoperatively in a combined
modality approach to esophageal Ca in hopes of controlling occult metastatic
disease and improving the resectability rate.

„ Platinum doublet is preferred over single agents
„ Cisplatin plus 5-FU or docetaxel are commonly used combinations

Regimens:
„ Paclitaxel and carboplatin
„ Cisplatin and 5-FU or capecitabine
„ Oxaliplatin and 5-FU or capecitabine
„ Paclitaxel or docetaxel and cisplatin
„ Carboplatin and 5-FU
„ Irinotecan and cisplatin
„ Oxaliplatin, docetaxel and capecitabine
„ Epirubicin, cisplatin and 5-FU (Only for adenocarcinoma)

Radiotherapy
„ Curative
ƒ Radical RT
ƒ Pre-Op RT
ƒ Post Op RT
ƒ Concurrent chemo-radiation
„ Palliative
„ EBRT
„ Brachytherapy

EBRT Techniques
„ Patient Positioning:
ƒ CERVICAL ESOPHAGUS: Supine with arms by the side
ƒ MID AND LOWER THIRD:
‚ SUPINE With arms above their head if AP – PA portals are being planned
‚ PRONE if posterior obliques are being included.
• Esophagus is pulled anteriorly and spinal cord can be spared.

„ IMMOBILISATION :
ƒ Perspex cast
ƒ Vertebral column should be as parallel to couch as possible.
„ Barium swallow contrast to delineate the esophageal lumen and
stomach.

EBRT – Cervical Esophagus
Field Portals:
„ AP – PA foll. by opposed oblique pair.
„ 2 anterior obliques and 1 posterior field.
„ 2 posterior obliques and 1 anterior field
„ 4 field box with soft tissue compensators foll by obliques ( Univ of
Florida tech )

„ SUPERIOR BORDER: At C 7
„ INFERIOR BORDER : At T 4 ( carina )
„ 2 cm lateral margins.
„ SC nodes irradiated electively.
„ SC nodes will be underdosed if oblique portals are used to treat
primary; can be boosted by a separate field if required.

EBRT – Mid & Lower1/3rd

 AP – PA followed by 1 Ant and 2 Post oblique pair
 4 FIELD : AP-PA & opposed laterals – for mid 1/3rd lesions with
patient in prone position.
 AP-PA upto 43 Gy foll by 2 Post obliques upto 50 Gy ( gross disease
boosted to 60 Gy )

„ SUPERIOR BORDER: 5 cm proximal to superior extent of disease.
„ INFERIOR BORDER:
ƒ MID 1/3RD – AT GE jn. As visualised by Barium swallow
ƒ LOWER 1/3RD - Coeliac plexus ( L 1 ) to be included.

Radiotherapy for
CA esophagus

EBRT - DOSES
„ Energy
ƒ 6 – 10 MV linac or Co60

„ Chemoradiation:
ƒ 50.4 Gy in 28 # at 1.8 Gy per #
ƒ Boost to 60 – 66 Gy for residual disease

„ Radical RT:
ƒ 45 Gy / 25 # / 1.8 Gy per #
ƒ boost with 2 cm margin to total dose of 60Gy

„ Dose limitations
ƒ Spinal cord Dmax:45 Gy at 1.8 Gy/fx
ƒ Lung: Limit 70% of both lungs <20 Gy
ƒ Heart: Limit 50% of ventricles <25 Gy

Brachytherapy (Intraluminal)

„ As a boost after EBRT or as a palliative measure
„ Local control of 25% - 35 in palliative setting
„ In curative setting, addition of brachytherapy does not improve
results compared to Chemoradiation.
„ Limit dose to critical structure
„ Dose escalation to primary
„ Relief bleeding, pain and improves swallowing status in palliative
setting.

American Brachytherapy Society Guidelines

Patient selection:
ƒ Primary tumor length ≤ 10 cm length
ƒ Tumor confined to esophageal wall
ƒ Thoracic esophagus location
ƒ No nodal / systemic metastasis.

Contraindications:
ƒ T E fistula
ƒ Cervical esophagous location
ƒ Stenosis which cannot be bypassed

Contd…

„ EBRT 45 – 50 Gy in 1.8-2.0Gy /#,5#/wk
‚ HDR – 5 Gy x two # one week apart , 2 – 3weeks after EBRT.
‚ LDR – single 20 Gy # @ 0.4 – 1.0 Gy per hr, 2 -3 weeks after EBRT.
„ Never concurrently with chemotherapy
„ Ext diameter of applicator must be 6 – 10 mm.
„ Active length : visible tumor by UGI scopy plus 1 – 2 cm proximal &
distal margin.
„ Dose is prescribed 1 cm from mid source or mid dwell position.

Trials – RT alone
„ No randomized trials of RT Vs Sx
„ 5 yr survival with conventional RT : < 10%
„ Tumors < 5 cm , 5 yr survival : 20%
„ Stage wise 5 yr survival:
ƒ Stage I – 20%
ƒ Stage II – 10%
ƒ Stage III – 3 %
ƒ Stage IV – 0%

Contd…

„ For cervical esophagus, cure rates were similar with Radical RT or
Sx alone.

„ RT or Sx alone DOES NOT alter the natural history of the disease.

„ RTOG 8501: RT Vs Chemo RT
ƒ Better LRC and improved OS with ChemoRT

 RT alone should be used for palliation or in medically unfit patients.

Trials– PreOP RT
„ Principle:

ƒ ↑ resectability, ↓ likelihood of tumor dissemination during Sx ,
↑ radioresponsiveness due to unaltered blood supply
ƒ 5 randomised trials ,shows no apparent clinical benefit to use
of preop rt alone except,
ƒ Only one trial ( Huang et al ) showed survival advantage of
46% Vs 25% with 40 Gy RT
ƒ Recent meta analysis Oesophageal Cancer Collaborative Group
study showed no clear survival advantage.

 No difference in resectability rates, LRC or survival with pre-op RT

Trials– PostOP RT
„ Advantages:
ƒ Treat areas at risk for recurrences while minimizing
dose to OAR.
ƒ Patients with node negative , completely resected T1
/ T2 tumors can be excluded.

„ Disadvantage:
ƒ Tolerance of stomach or bowel used for
interpositioning.

Contd…

„ 2 randomised trials:
ƒ Peniere et al :-
‚ 221 pts, mid / low 1/3rd growth
‚ RT : 45- 55 Gy @ 1.8 Gy per #
‚ 3 yrs -  local failure rate ( from 35% to 10%)
- no significant disease free survival.
ƒ Fok et al :-
‚ 130 pts , RT – 49 Gy @ 3.5 Gy per #
‚ Local failure rate  in patients who had palliative resection
( from 46% to 20% )
‚ No difference for completely resected patients

 Post op RT improves local control, but does not confer any survival
advantage.

Trials– Chemoradiation

ChemoRT Vs RT Alone
„ RTOG 8501 INTERGROUP TRIAL:
ƒ 121 pts: 60 pts RT alone – 64 Gy @ 2 Gy per #
61 pts chemoRT – 50 Gy RT +
5 FU + CDDP – on 1 , 5 , 8 & 11 weeks
ƒ Median survival : 8.9 Vs 12.5 months
ƒ 5 yr survival : 0% Vs 30 %
ƒ Distant mets @ 5 yrs: 40% Vs 12 %
ƒ Acute toxicity : 25% Vs 44 %
„  Median & overall survival, LRR and Acute toxicity in Chemo RT
arm.

 Chemoradiation is a standard Non-surgical Tx.

Contd…

RT dose escalation in Chemo RT
„ Intergroup 0123 TRIAL – 218 pts
ƒ Chemoradiation - either 50.4 Gy or 64.8 Gy
ƒ No significant difference in median survival, 2 yr survival or loco-
regional failure.

 Intensification of RT dose beyond 50.4 Gy(in combination with
chemotherapy ) does not improve results.

Contd…

PRE OP CHEMO RT Vs Sx ALONE
„ 44 Randomised trials
„ 2 studies showed  in local recurrence
ƒ Urba et al – 19 % Vs 42 %
ƒ Bosset et al ( EORTC ) – 28% Vs 40%

„ One study showed significant survival benefit at 3 yrs (in pts who had
a pathologic CR )
ƒ Urba et al – 64% Vs 19%

„ One study (Walsh et al) showed benefit in median (16 Vs 11 months )
and overall survival at 3 yrs ( 32 Vs 6%)

 Results support TRIMODALITY approach.

Pre-operative Chemotherapy

The role of preoperative
chemotherapy alone is
controversial, according to
mixed results from clinical
trials.

Stage Recommended treatment
Stage I–III and IVA definitive chemo-RT (preferred for cervical esophagus)
resectable
medically-fit
Or, Pre-op chemo-RT → surgery. Surgery preferred for adenocarcinoma
regardless of response to chemo-RT.
Or, surgery. (noncervical T1N0 and young T2N0 patients with primaries
of lower esophagus or gastroesophageal junction.
Indications for post-op chemo-RT include: unfavorable T2N0, T3/4,
LN+, and/or close/+ margin.
Stage I–III inoperable Definitive chemo-RT
Stage IV palliative Concurrent chemo-RT (5-FU + cisplatin, 50 Gy) or RT alone (e.g., 2.5
Gy × 14 fx) or chemo alone or best supportive care.
Pain: medications ± RT
Bleeding: endoscopic therapy, surgery, or RT

Current approach

„ EBRT using 3D-CRT to a total dose of 50.4 Gy (1.8 Gy per daily fraction) is
standard.
„ IMRT is often utilized to minimize exposure to adjacent structures.
„ Proton beam in combination with chemotherapy is being explored.
„ Targeted biologic agents added to standard cytotoxic chemotherapy is
being explored

Conclusion
„ Esophageal cancer is the 7th leading cause of cancer deaths.

„ Adenocarcinoma now accounts for over 50% of esophageal cancer in the
USA, due to association with GERD & obesity.

„ Dysphagia and weight loss are the two most common presentations in
patients with esophageal cancer.

„ Endoscopic ultrasound (EUS) is necessary to accompany a complete workup
for proper staging and diagnosis of esophageal cancer.

„ Surgery is the standard of care for early-stage esophageal cancer.

„ Preoperative chemotherapy and radiation is the standard option for locally
advanced esophageal cancer in surgically eligible patients.

ChemoRT followed Sx Vs.ChemoRT

„ Patient undergoing surgery
have worse quality of life.

„ Surgery following combined
CRT appears to improve
local control, its impact on
ultimate survival remains
controversial.

Figure: A proposed treatment
algorithm for esophageal cancer.

Carcinoma oesophagus

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