This document discusses esophageal cancer. Some key points: - Squamous cell carcinoma and adenocarcinoma are the most common histologies. Risk factors include smoking, alcohol, obesity, and Barrett's esophagus. - Staging uses the TNM system. Treatment depends on stage but may include surgery, chemotherapy, radiation therapy, or a combination. - For locally advanced stages, neoadjuvant chemoradiation can improve resectability and survival compared to surgery alone. The MAGIC trial showed improved survival with perioperative chemotherapy compared to surgery alone. - Prognosis remains poor with 5-year survival rates of 15-20%, though outcomes have improved with multimod

1. Dr Sneha George

2.  7th most common carcinoma worldwide
 MC histology – Squamous cell carcinoma
 Adenocarcinoma is on the rise in developed
countries
 5 year survival – 15 to 20%
 Peak age of incidence – 6th -7th decade
 Risk factors
SCC – Alcohol , smoking , diet, achalasia
Adenocarcinoma – Obesity, Barretts esophagus
 Adenocarcinoma – lower 1/3rd (65% of lesions)

3. Staging System, T and N for
Esophagus Cancer
Tis T1
intramucosal
T1
submucosal
aorta
T4T3
T2
N0
N1
1-2
nodes
Mucosa
N2
3-6 nodes
N3
7+nodes
Muscularis
propria
Submucos
a

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

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

7. T1
T2
T3
TNM Staging By CT
T4

9.  Surgery
 Chemotherapy
 Radiation therapy
 Combined modality

10. Locoregional cancer
Stages (I-III, IVA)
Ca esophagus
Metastatic disease(IVB)
Palliative therapy
Medically fit for Sx,
Resectable.
Unresectable T4, IVA
or Medically unfit for Sx,
able to tolerate CRT
Medically unfit for
SX and CRT
Cervical Lesions: CRT Thoracic disease:
Surgery+/– RT/CRT
depending on HPR & LN
Location of lesion
R0 LN-ve SCC= observe. R0 LN-ve Aca = >T2---CRT. R0 LN +ve SCC= CRT
R0 LN +ve Aca=CRT R1,R2= CRT/ palliation if poor GC
RT/ CRT

11.  Tis – Endoscopic resection or ablation
- Esophagectomy
 T1a – Endoscopic resection or ablation
- Esophagectomy
 T1bNO – Esophagectomy
If superficial T1b – Endoscopic resection

12.  T1bN+ or T2-T4a – Preop chemoradiation
-> Surgery
- Chemoradiation
- Esophagectomy (low risk)
 T4b - ChemoRT
- Chemotherapy alone or radiation alone
- Palliative care

13.  T1-T2 tumour with dysphagia of grade 1
and 2
 Lesion <5 cm
 Disease confined to the thoracic and lower
esophagus
 Good GC
 No co-morbid illnesses

14. Esophagectomy
SURGERY IN CA ESOPHAGUS
Endoscopic mucosal resection(EMR)
Transthoracic approach Transhiatal approach
(Lower esophageal lesions)
Right (IVOR LEWIS)
thoracotomy
Left thoracotomy
(Mid esophageal lesions) (GE junction lesions)
Ind: Tumours<2 cm; WD to MD SCC/adenoca without
invasion beyond mucosal layer OR Ulceration OR LVI)

15.  ROLE - Radical ( early stage)
- Palliative ( advanced stage)
 MODALITIES
- Radiotherapy alone
- Combined with surgery – Pre op RT
- Post op RT
 TECHNIQUES
- EBRT
- Brachytherapy

16.  Carcinoma of upper 1/3 and middle 1/3 of
esophagus
 Tumour < 5 cm in length
 Stage I,II
 No mediastinal spread
 No distant metastasis
 Good general condition
CONTRAINDICATION:
Infiltration of the tracheobronchial tree and
aorta

17.  PATIENT POSITIONING:
◦ CERVICAL ESOPHAGUS: Supine with arms by the side
◦ MID AND LOWER THIRD:
 SUPINE if AP – PA portals are being planned
 PRONE if posterior obliques are being included
 IMMOBILISATION :
◦ Perspex cast
◦ Vertebral column should be as parallel to couch as
possible.
 Barium swallow contrast to delineate the
esophageal lumen and stomach.

18.  AP – PA foll. by opposed oblique pair.
 2 anterior obliques and 1 posterior field.
 2 anterior obliques and 1 anterior field
 4 field box with soft tissue compensators followed
by obliques
 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
photon field if required.

19.  AP – PA followed by 1 Ant and 2 Post oblique pair
( coning down )
 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:
◦ MID 1/3RD – AT GE jn. As visualised by Barium swallow
◦ LOWER 1/3RD - Coeliac plexus ( L 1 ) to be included.

20.  ENERGY – 6-10MV LINAC or Co-60
 CHEMORADIATION :
50.4Gy/28F/5.3 weeks @ 1.8Gy/F
Boost to 60-66Gy for residual disease
 RADICAL RT
45 Gy/ 25 F/5 weeks @ 1.8Gy/F
Boost with 2 cm margin to a total dose of 60 Gy
 PALLIATIVE RT
35Gy/15F/3 weeks
30Gy/10F/2 weeks

21.  Spinal cord Dmax : 45 Gy @ 1.8Gy/F
 Lung : V70 < 20 Gy
 Heart : V50 < 25 Gy

22.  CT simulation
 Positioned and immobilised
 Arms are placed overhead and knee support under
the legs
 Palpable neck disease – radiopaque wire
 Oral contrast to delineate the esophagus
 Arterial phase IV contrast to delineate mediastinal
and abdominal vascular nodal basins including celiac
axis
 Tumour and vital structures are outlined on each slice
of CT
 3D treatment plan is generated

23.  Better tumour dose distribution with an increase in
normal tissue toxicity
 GTV : CT – radial and regional extent
UGIE – longitudinal extent
EUS – longitudinal and radial extent
 CTV - 3-4 cm longitudinal margin (additional 1 cm for PTV )
- Radial expansion 1.5-2 cm.
Location wise specifications in CTV :
Middle 1/3rd : include subcarinal LN
Upper 1/3rd : include Paratracheal and SCF LN
Lower 1/3rd : Celiac nodes

24.  Thoracic hilar and Ant mediastinal nodes not included
unless grossly involved.
 GEJ involvement: Pericardial LN+, celiac LN +, nodal tissue
in porta hepatis, gastrohepatic ligament, left gastric artery,
splenic artery, and splenic hilum included

25.  Boost after EBRT
 Palliative setting
 ABS guidelines:
Patient selection criteria
- Primary tumour length </= 10 cm
- Tumour comfined to esophageal wall
- Thoracic esophagus
- No nodal/systemic metastasis

26.  CONTRAINDICATIONS
- Tracheo-esophageal fistula
- Cervical esophagus
- Stenosis that cant be bypassed
EBRT 45-50 Gy in 1.8-2 Gy/F in 5 weeks
2-3 weeks later
HDR : 5Gy x 2F one week apart
LDR : 20 Gy single fraction at 0.4-1 Gy/hour

27.  External diameter of applicator : 6-10
mm
 Active length : Visible tumour by UGIE +
1-2 cm proximal and distal margin
 Dose is prescribed 1 cm from mid source
or mid dwell position

28. PRE OP RT
To increase local control by
- Reduced bulk of tumor and local infiltration
- Increased resectability of tumor
- Reducing dissemination at the time of surgery
-Treating micro metastasis in regional LN and lymphatics
RESULTS:-

29. Dose= 30-40Gy
Higher doses: poor Surgical factor, increased friability.
CONCLUSION:
No significant difference in survival, local failures and
resectability rates between those receiving preop RT and those
receiving Sx alone.

30. POST OP RT
INDICATIONS:-
- Residual disease
R1/R2 RESECTION
R0 RESECTION with T2,3 AdenoCa
- Adjacent visceral invasion
- Lymph node metastasis
ADVANTAGES
- Patients with pathological T1N0 or metastatic disease may be spared
RT
- Knowledge of pathological staging for appropriate Adj Rx selection
- Allows to treat areas at risk for recurrence while sparing other wise
normal radiosensitive structures and decreasing toxicity
DISADVANTAGES
Limited tolerance of tissue after gastric pull-up or intestinal
interposition

31. Dose: 40 Gy -50 Gy/4 -5 wk
LTS:
French trial (n=221): No significant survival difference was seen
in patients receiving post op RT versus Sx alone.
- However, in patients without LN involvement, LRR was
significantly lower in post op RT gp (90% vs 65%)
Xiao et al (n=549): Local control and survival were improved in
patients receiving post op RT.
Fok et al (n=130): No difference in local control and median
survival for post op RT group
- No difference in median survival with post op RT

32. CONCLUSION:
- Postop RT may decrease local recurrence,
particularly in the setting of involved margins
- The impact on OS remains less clear.

33. Minsky BD, Pajak T, Ginsberg RJ, et al: INT 0123 (RTOG 94-05) phase III trial of combined modality therapy for esophageal cancer: high dose
(64.8 Gy) vs. standard dose (50.4 Gy) radiation therapy. J Clin Oncol 2002; 20:1167-1174

34.  Results:
(1) For the 218 eligible patients, there was no
significant difference in median survival, 2-year
survival (31% v 40%), or local/regional failure
and local/regional persistence of disease (56% v
52%) between the high-dose and standard-
dose arms.
(2) 11 treatment-related deaths occurred in the
high-dose arm compared with two in the
standard-dose arm, seven of the 11 deaths
occurred in patients who had received 50.4 Gy
or less.
The higher radiation dose did not increase survival or
local/regional control. Although there was a higher treatment-
related mortality rate in the patients assigned to the high-dose
radiation arm, it did not seem to be related to the higher radiation
dose. The standard radiation dose for patients treated with
concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy

35.  No data proving that chemotherapy alone
provides improved survival or palliation. Partial
response, not long-term remission, is the rule
 Indications
◦ Used in combination with radiation for locally
advanced cancers (to improve resectability and to
control occult disease)
◦ Used as single treatment modality in stage IV
disease

36.  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)

37. NEOADJUVANT CCT
Kelson et al( n= 440)
CDDP(100mg/m2) + 5FU(1000mg/m2) X 3wkly; 3 cycles+ Sx Vs Sx
No improvement in survival( 3yr OS 23%vs 26%), local failure( 32% vs 31%) and
distant metastases development( 41% 50%).
Medical research Council trial(n=802)
CDDP(80mg/m2 D1 and D22) + 5FU(1000mg/m2 D1-4, D22-25) +Sx
Pateints receiving NACT had a statistically improved 2yr survival
(43% vs 34%).

38. MAGIC TRIAL 503 patients
Pre and post operative Epirubicin, cisplatin, 5-FU (250 ptns )
Vs
Surgery alone (253 patients )
Median survival 24 months Vs 20 months
Five-year OS was improved by 13% (36% vs 23%; P < .001) in the
chemotherapy group.
There was no improvement in the rate of curative resection with
preoperative chemotherapy
No pathologic complete responses were observed.

39. COMBINED MODALITY THERAPY (CCT +RT)
Rationale
- Improving local control by overcoming radioresistance
- Eradicating micrometastasis to decrease systemic failure rate
- Increased tumor resectability
Advantages
- Independent action of each modality
- Additive antitumour activity
-To achieve histopathologically negative disease which correlates with
better survival

40. Short term complications
•Transient myelosuppression
(30%)
• Esophagitis
• Dysphagia
• Pneumonitis
• Perforation with fistula or
hemorrhage
• Skin changes: hair loss,
redness
• Pericarditis
• Nausea/ vomiting
• LOW/LOA
Long term complications
• Stenosis/ stricture
• Pneumonitis/ pulmonary
fibrosis
• Esophagotracheobronchial
fistulae
• Aortic rupture and hemorrhage
• Pericarditis with pericardial
constriction
• Transverse myeiltis
• Myocardial damage
• Radionecrosis of bone
COMPLICATIONS OF CRT

41. Cooper JS, Guo MD, Herskovic A, et al: Chemoradiotherapy of locally advanced esophageal cancer. Long-term follow-up of a
prospective randomized trial (RTOG 85-01). JAMA 1999; 281:1623-1627

42.  The incidence of local failure as the first site of failure
(defined as local persistence plus recurrence) was also
lower in the CMT arm (47% versus 65%)
Cooper JS, Guo MD, Herskovic A, et al: Chemoradiotherapy of locally advanced esophageal cancer. Long-term follow-up of a
prospective randomized trial (RTOG 85-01). JAMA 1999; 281:1623-1627

43.  75 patients with squamous cell cancers (92%) or
adenocarcinomas (8%) of the thoracic esophagus
 RTOG 85-01 CMT regimen (5-FU/cisplatin/50 Gy) 
boost during cycle 3 of chemotherapy HDR
intraluminal brachytherapy.
 High dose rate brachytherapy was delivered in
weekly fractions of 5 Gy during weeks 8, 9, and 10,
Following the development of several fistulas, the
fraction delivered at week 10 was discontinued

44.  The complete response rate was 73% with a
median follow-up of only 11 months, local
failure as the first site of failure was 27%.
 Acute toxicity included 58% grade 3, 26%
grade 4, and 8% grade 5 (treatment-related
death)
 The cumulative incidence of fistula was
18%/year and the crude incidence was 14%.
Of the six treatment-related fistulas, three
were fatal.

45.  The chemotherapy and radiation doses delivered in
the combined-modality therapy arm of RTOG 85-
01 were intensified.
 The regimen was modified as follows:
(1) 5-FU continuous infusion was increased from 4
to 5 days;
(2) total number of chemotherapy cycles was
increased from four to five
(3) three cycles of full-dose neoadjuvant 5-FU and
cisplatin were delivered before the start of
combined-modality therapy
(4) radiation dose was increased from 50 to 64.8 Gy.
Minsky BD, Neuberg D, Kelsen DP, et al: Final report of intergroup trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of
neoadjuvant chemotherapy plus concurrent chemotherapy and highdose radiation for squamous cell carcinoma of the esophagus. Int
J Radiat Oncol Biol Phys 43:517-523, 1999.

46.  The response, local/regional control, and survival
rates for INT 0122 were similar to those reported in
the combined modality arm of RTOG 85-01.
However, the incidence of treatment-related
mortality was higher (9% v 2%).
Minsky BD, Neuberg D, Kelsen DP, et al: Final report of intergroup trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of
neoadjuvant chemotherapy plus concurrent chemotherapy and highdose radiation for squamous cell carcinoma of the esophagus. Int
J Radiat Oncol Biol Phys 43:517-523, 1999.

47.  366 patients with resectable Sq. cell and
Adenocarcinoma of esophagus and GEJ,
 T2-3 N+M0
 Randomized arms inculde
(1) surgery alone
(2) Pre-operative RT 41.4 Gy/ 23 Fr +
Carboplatin (AUC 2) and paclitaxel (50
mg/m2) weekly + Surgery.
Van Hagen P et al., properative chemoradiation for esophogeal or junctional cancer. NEJM 2012 May 31,
366:2074

48.  More patients in combined modality arm had
– ve margin R0 resection (92 Vs 69 %)
 pCR was achieved in 29% in CMT arm
 Median OS was higher in CMT than surgery
alone ( 49.9 Vs 24 months)
 5 years OS was higher in CMT ( 47 Vs 34%)
Van Hagen P et al., properative chemoradiation for esophogeal or junctional cancer. NEJM 2012 May 31,
366:2074

49. CRT vs Surgery alone
No randomized trials comparing the two modalities
easons for selection bias against non surgical therapy
Patients having medical contraindications for Sx, unresectable primary and
metastatic disease are selected for non surgical therapy
 Surgical series report results based on pathological staging whereas non
surgical series report results based on clinically staging
 The intensity of Chemotherapy and doses of radiation have been suboptimal
in most historic series.
RT alone Sx alone ChemoRT
5 year survival 0% 20-24% 30%
Local recurrence 59% 32-45% 45%
Distant mets 40% 31-40% 12%

50. TRIAL REGIMEN PATH CR
(%)
3 YR SURVIVAL
Urba et al n=133 5 FU- CDDP-V/45Gy Sx 28 CMT:30%; Sx alone:16%
Bosset et al (EORTC) n=23 CDDP/37Gy Sx 20 CMT:33%; Sx alone:36%
Walsh et al n=139 5 FU-CDDP/40Gy Sx 22 CMT:32%; Sx alone:6%
Bumeister et al n=27 5 FU-CDDP/40Gy Sx 16 CMT:35%; Sx alone:31%
Tepper et al n=128 5 FU-CDDP/50Gy Sx 40 CMT:39%; Sx alone:16%
CHEMORADIATION FOLLOWED BY SURGERY
RATIONALE:
Improved resectability
Eradicates micromets
Non responders to induction CRT may benefit by Sx
CONCLUSION: significantly Improved LC and OS
DOSE: Cisplatin 30 mg / m2 D1- D4 + 5 FU 325 mg / m2 D1 – D4 infusion
EXRT 30 Gy / 10 # / 2 wks
Sx after 3-4 wks

51.  Better tumour response
 Improved local control and distant disease
control
 Incorporated with concurrent chemo radiation
schedules
 Egs :
- Cetuximab
- Trastuzumab
- Celecoxib

52.  For symptomatic relief mainly dysphagia
 METHODS
- Surgical palliation – resection and reconstruction
- increased morbidity
 Endoscopic dilatation – 15 mm is required
- Repeat dilatation is needed
- Esophageal plastic or
metallic stents

53.  To control primary disease and distant
metastasis
 Dose : 30 Gy in 10 F
7 Gy x 3
- Laser ablation with or without intraluminal
brachytherapy

54. THANK YOU