1. Management of carcinoma
esophagus
DR BHARTI DEVNANI
MODERATOR:- DR ANJALI K. PAHUJA

2. Localised disease Metastasis
Definitive therapy Palliative therapy
Diagnostic workup
.
At the time of diagnosis, approximately 80% patients
have locally advanced or distant disease

3. EVOLUTION OF TREATMENT
Non surgical treatment
 Radiation therapy alone
 Combined modality therapy(CT+RT)
 Intensification of the radiation dose
Surgical treatment
Sx alone
Sx+adjuvant
Preop CT + Sx

4. RT ALONE

5. 6
RADIATION ALONE
AUTHOR NO OF PTS DOSE 2 YRS
SURVIVAL
5 YRS
SURVIVAL
Pearson 208 50Gy/4Wks NA 17%
Beatty et al 344 >40Gy to
> 50Gy
21% 0%
Schuchman
n et al
127 <45Gy
>45 Gy
0%
0%
Newaishy
et al
444 50-55Gy/4
Wks
19% 9%
Okawa et al 96 NR 9%(I-20%,II-
10%,III-3%,IV-
0%)
Lederman
et al
263 11%(yrs) 7%

6. COMBINED MODALITY TREATMENT
(CT+RT V/S RT ALONE)

7. RTOG 85-01 TRIAL(RT ALONE V/S CMT)
R
A
N
D
O
M
I
S
E
Wk 1
50Gy/25 fractions
Wk 5 Wk 11
CDDP 75mg/m2 Day 1 and 5-FU 1gm/m2 C.I. day 1- 4
CT+RT
RT
Wk 8
64Gy/32 fractions

8. RESULTS OF RTOG 85-01 TRIAL
Comp-
liance
Gr III
toxicity
Gr IV Gr V Local
failure
Dist
failure
Median
and 5yr
survival
CT+RT
(n=61)
54% 44% 20% 3% 43% 22% 12.5 mo,
27%
RT
(n=60)
83% 25% 3% 0 64% 38% 8.9 mo,
0%
P-value Sig Sig Sig Sig Sig Sig
p<0.0001
All patients who received RT alone were dead of disease by 3 years.
Established chemoradiation as the conventional nonsurgical treatment
for esophageal cancer
Herskovic A et al. NEJM 1992;326:1593-1598

9. 10
CONCURRENT CT+RT- META ANALYSIS OF 11RCT
Cochrane Database of Systematic Reviews

10. RESULTS OF METANALYSIS
 Concomitant RTCT provided significant reduction in
mortality with a HR of 0.73.
 The absolute survival benefit for RTCT at 1yr and 2 yr
was 9%and 4% respectively.
 There was an absolute reduction of local recurrence
rate of 12%

11. INTENSIFICATION OF RADIATION DOSE
(BY BRACHYTHERAPY BOOST)

13.  The cumulative incidence of fistula was 18%/year
and the crude incidence was 14%.
 Esophageal fistulas were treatment-related rather
than tumor-related of the six treatment-related
fistulas, three were fatal .
 Occurred in the region of the brachytherapy.
 Five of the six patients developing fistulas received
15 Gy brachytherapy dose. (median-3.9 months)
 The other patient received just one fraction of 5 Gy
and developed a fistula within 0.5 months.

14. HIGH DOSE V/S STANDARD RADIATION
DOSE

16. 17
R
A
N
D
O
M
I
S
E
Wk 1
50.4Gy/28 fractions
Wk 5 Wk 13
CDDP 75mg/m2 Day 1 and 5-FU 1gm/m2 C.I. day 1- 4
Standard
CT+RT
CT +
High dose RT
Wk 9
64.8Gy/36 fractions
Wk 1 Wk 5 Wk 11 Wk 15
Minsky BD et al. JCO 2002;20:1167-1174

17. No significant difference in
survival(p=NS)
MS-18 v/s 13 months
2 yr survival—40% v/s 31%
No significant difference in time to first
failure(52% v/s 56%)
(local /regional failure or locoregional
persistance of cancer)
This trial demonstrated that for patients who receive concurrent chemotherapy
with radiation, higher doses of radiation therapy do not offer a
local/regional control or survival advantage.

18. PREOPERATIVE CHEMORADIATION
THERAPY

19. 20
PRE OP.CT+RT+S VS S
AUTHOR MEDI
AN
FOLL
OW
UP
REGIMEN NO
OF
PTS
Ro
resection/
Dist Met
PATH CR LOCOREG
FAILURE
3-Yr
Surviv
al
SURVIVAL
DIFF
Urba et al 8.2 5fu+cddp+Vbl+R
T+S
S
50
50
90 60%
90 65%
28
-
19%
42%
P=0.02
30
16
p=0.15
Boset et
al
4.6 Cddp+RT+S
S
143
138
81
69
26
---
34
36
NS
Walsh et
al
1.5 5fu+cddp+RT+S
S
58
58
NR
NR
25 32
6
P+0.01
Burmeiste
r et al
5.4 5fu+cddp+RT+S
S
128
128
80
59
16
---
35
30
NS
Tepper et
al
6.0 5fu+cddp+RT+S
S
30
26
NR
NR
33 13
15
39
16
P=0.008

20.  9 RCT
 1116 patients

21. Three-year survival (odds ratio 0.66,
95% confidence interval 0.47
to 0.92; P 0.016).
Rate of complete resection (odds
ratio 0.53, 95% confidence
interval
0.33 to 0.84; P 0.007).

22. Compared with surgery alone, neoadjuvant
chemoradiation and surgery
 Improved 3-year survival
 Reduced local-regional cancer recurrence.
 Higher rate of complete (R0) resection.
 Pathological complete response in 21% patients
 Survival benefit was most pronounced when CT+RT
were given concurrently instead of sequentially

24. Lancet Oncol 2011; 12: 681–92

26. Provides strong evidence for a survival benefit of neoadjuvant
chemoradiotherapy or chemotherapy over surgery alone in patients with
oesophageal carcinoma. clear advantage of
neoadjuvant chemoradiotherapy over neoadjuvant chemotherapy has not
been established.

27. CAN SURGERY BE AVOIDED

28. 46 Gy
20 Gy

29.  In patients with locally advanced thoracic esophageal
cancers, especially epidermoid, who respond to
chemoradiation, there is no benefit for the addition of
surgery after chemoradiation compared with the
continuation of additional chemoradiation.
 chemoradiation alone entailed fewer early deaths and a
shorter hospital stay
 More locoregional relapses.
 Because clinical prognostic factors donot help in
choosing between both strategies, further studies
comparing surgery and chemoradiation should search
for newpredictive factors and evaluate new tools to
detect early responders.
 PET scan was reported to discriminate responders from
nonresponders as early as 14 days after starting
chemoradiation and should be re-evaluated in future
studies.

30. The study suggests that there is no difference in clinical toxicity profiles or
survival outcomes with either definitive chemoradiotherapy or chemoradiation
followed by surgery in management of locally advanced esophageal cancer.

31.  Future studies are necessary to investigate dose
escalation of chemoradiotherapy, thereby reducing
the risk of treatment failures in patients treated
without surgery.

35. RADIATION

36. The design and delivery of radiation therapy for
esophageal cancer requires a knowledge of the –
 Natural history of the disease
 Patterns of failure
 Anatomy,
 Radiobiologic principles.
 Use of proper equipment
 Implementation of methods to decrease treatment-
related toxicity
 Close collaboration with the physics and technology
staff are essential.
 As radiation oncology is both an art and a science.

37. RADIOTHERAPY
Curative
Dose-50.4 Gy/28#
 Conventional
 Conformal
 3 D CRT
 IMRT
 IGRT
 Arc
 Respiratory gating
 Proton
Palliative
EBRT
Dose-30 Gy/10#
Brachytherapy
12 Gy/#
18 Gy/3#

38. TECHNIQUES OF RADIATION THERAPY
 External beam radiotherapy
 Important considerations for RT
 Nearby vital structures: spinal cord. lungs, heart
 Movement in target tissue and vital structures: lungs,
heart
 Variable density of tissues: lungs

39. TECHNIQUES OF RADIATION THERAPY

40. SIMULATION
 Extent of the disease should be known based on imaging
 Barium swallow,
 CT,
 PET
 Endoscopy.
 During simulation, the patient is positioned, straightened, and
immobilized on the simulation table.
 Arms are generally placed overhead.
 Palpable neck disease should be marked with a radio-
opaque wire
 Administration of oral contrast to delineate the esophagus is
used.
 Some authors recommend placing the patient in the prone
position for treatment to displace the esophagus away from
the spinal cord

41. Conventional technique
TREATMENT PORTALS
Parallel opposed AP-PA fields
EBRT TECHNIQUES
Initial phase (39.6-41.4 Gy)
- 5cm prox and distal margins
- 2 cm lateral margins

42. Off cord Boost: After 40-44Gy
3 field technique -- one direct anterior and two lateral/ posterior oblique
Advantages
- Homogeneous dose distribution
- Tumor better covered
- Critical organs are out of the field

43. ‘T’ shaped AP-PA field:
Upper cervical esophagus lesion
- Treated from laryngopharynx to carina
- Supraclavicular and upper mediastinal LN s irradiated electively
AP-PA fields with lung shielding
BORDERS:
Superior: Thyroid notch
Lateral : Junction of medial 2/3rd and lateral 1/3rd clavicle
Lower: Adequate margins from lesion (include upper mediastinal LNs)
Shielding: 5 HVL lead shield from 1cm below the
Clavicles
Lung correction factor
-Co60 - dose decreased by 4%/cm
- For 4 MV - 3% /cm
- 10 MV -2 %/cm of lung

44. NORMAL TISSUE TOLERANCE
Organ TD5/5 Gy TD50/5 Gy Field size
Spinal cord 47
50
-
70
20cm
5-10cm
Heart 40
60
50
70
Whole
1/3rd
Lung 17.5
45
24.5
65
Whole
1/3rd

45. APPROPRIATE TARGET VOLUME AND
NEED OF ELECTIVE NODAL
IRRADIATION IN CONFORMAL
THERAPIES

46. •In patients treated with 3D-CRT for esophageal SCC, the omission of elective
nodal irradiation was not associated with a significant amount of failure in
lymph node regions not included in the planning target volume.
•Local failure and distant metastases remained the predominant problems.
•A longitudinal margin of 3 cm from the GTV to the CTV1 is probably enough

47. BASIS OF OMITTING ENI
Recurrence was with in GTV

48. 1. Recurrene pattern(in-field)
Predominant failure pattern in with esophageal SCC was local
in-field or distant failures. Regional nodal recurrence (out-of-
field) was infrequent (8%) in the absence of elective node
irradiation.
2. Biological behavior of the disease
Esophageal cancer is characterized by a high rate of nodal
involvement and its spread pattern is not always predictable.
Also, skip node metastases are frequently observed. Thus the
biological behavior of this disease makes it difficult to define in
advance the extent of coverage of elective nodal irradiation.
3. Toxicities
If distant lymph node areas were irradiated prophylactically,
patients would then experience more severe radiation
complications and have a poorer treatment tolerance.

49. In CRT for esophageal SqCC, ENI was effective for preventing regional nodal
failure. TheUPPER THORACIC esophageal carcinomas had significantly more local
recurrences than the middle or lower thoracic sites.

50. No global consensus on whether or not
ENI should be performed.

51. POST-OPERATIVE MANAGEMENT IN
CASES OF UPFRONT SURGERY

52. WHEN NO PRE –OP RT+CCT RECIEVEED

53. RECEIVED PRE-OP RT+CCT

54. TARGATED THERAPIES

55. TRASTUZUMAB + CHEMOTHERAPY IN
ADVANCED HER2+ GASTRIC CANCER: TOGA
STUDY
 Rationale: a subpopulation of gastric cancers overexpress HER2
*
(n = 584)
R
Patients with
advanced
gastric
adenocancer
screened for
HER2 status
(N = 3803)
Stratified by ECOG PS,
advanced vs metastatic, gastric vs GEJ,
measurable disease, capecitabine vs 5-FU
Patients with
HER2+
advanced
gastric cancer
(n = 810; 22% of
successful
screenings)
5-FU or Capecitabine* +
Cisplatin 80 mg/m2 q3w x 6 +
Trastuzumab 6 mg/kg q3w until PD
(8 mg/kg loading dose)
(n = 294)
5-FU or Capecitabine* +
Cisplatin 80 mg/m2 q3w x 6
(n = 290)
Bang YJ, et al. Lancet. 2010;376:687-697.

56. Outcome Chemotherap
y +
Trastuzumab
(n = 294)
Chemotherap
y Alone
(n = 290)
HR (95% CI) P Value
Median OS,
mos
13.8 11.1 0.74 (0.60-
0.91)
.0046
Median PFS,
mos
6.7 5.5 0.71 (0.59-
0.85)
.0002
Established transtuzumab and chemotherapy is a new standard of
care for Her-2 neu expressing advanced gastric and EGJ
adenocarcinoma.
Significant OS benefit
Safety profile were similar

57. PALLIATIVE CARE

58. IMPORTANCE OF PALLIATIVE CARE IN CA
ESOPHAGUS
Majority of the patients diagnosed with advanced
disease(80%) therefore palliation is an important
goal.

59. 1.Dysphagia
2.Obstruction
EBRT
BT
EBRT+CCT
Surgery
Endoscopic lumen restoration
Stenting
3.Pain(WHO pain ladder)
4. Nausea and vomitting (Antiemetics)
5.Bleeding
Acute bleeding
Chronic bleeding
6.Tracheo-oesophageal fistula

60. Fractionated BT is the best modality of palliation in comparison to all other
modalities.for advanced esophageal cancers. It offers best palliation both in
terms of survival(6.2) as well as symptom free duration
40% pts were free of dysphagia for one yr.
16Gy/2# or 18 Gy/3#

61. Versus

62.  Dysphagia improved more rapidly after stent placement than
after brachytherapy, but longterm relief of dysphagia was better
after brachytherapy.
 Stent placement had more complications than brachytherapy
which was mainly due to an increased incidence of late
haemorrhage .
 No difference for median survival (p=0·23).
 Quality-of-life scores were in favour of brachytherapy compared
with stent placement.
 Total medical costs were also much the same for stent
placement (€8215) and brachytherapy (€8135).
Due to better long-term relief of dysphagia with fewer
complications brachytherapy is recommended as the primary
treatment for palliation of dysphagia from oesophageal cancer.

63. BRACHYTHERAPY
Procedure
• After placing the patient in left lateral position, a fibre-optic endoscope is
passed.
• The esophagus will be evaluated for extent of residual tumor, presence of
ulcer and stricture.
• If suitable for brachytherapy, a stainless steel guide wire will be passed
through the biopsy channel of the endoscope and passed beyond the
tumor site
• Depending upon the site of lesion, the length of selectron boogie will be
adjusted by altering position of the mouth piece, so that lower end of the
boogie is 2cm beyond the lower limit of initial lesion.
• The boogie will be threaded over the guide wire, which is then withdrawn

64. BRACHYTHERAPY
Prescription
1 cm from the mid-source / mid-dwell position without
optimization

65. BRACHYTHERAPY ON TREATMENT

66. SURGICAL APPROCHES FOR
ESOPHAGOGASTRECTOMY
 Transthoracic approach
 Transhiatal approch

67. TRANSTHORACIC APPROACH
Right thoracotomy & laparotomy
 Ivor lewis
 Mckeown
(with cervical anastomosis)

68. APPROACHES TTE
IVOR LEWIS

69. APPROACHES TTE
MCKEOWN

70. •Transient myelosuppression (30%)
• Esophagitis
• Dysphagia
• Pneumonitis
• Perforation with fistula or
hemorrhage
• Skin changes: hair loss, redness
• Pericarditis
• Nausea/ vomiting
• LOW/LOA
• Stenosis/ stricture
Occurs in 60 % of cases
Stricture requiring dilatation-15-
20 %
• Pneumonitis/ pulmonary fibrosis
• Esophagotracheobronchial fistulae
• Aortic rupture and hemorrhage
• Pericarditis with pericardial
constriction
• Transverse myeiltis
• Myocardial damage
• Radionecrosis of bone
COMPLICATIONS OF CRT

71. PROBLEMS WITH TRIMODALITY
 Haematological toxicity – 30 %
 Mucositis Gr 3,4
 Oesophagitis
 Pulm complications (ARDS) 14 %
 Surgical complications -
 anastomotic leak 6 %
 Local recurrence 6 %
 Operative deaths 6 %
TOXICITY
TUMOUR CONTROL

72. MANAGING COMPLICATIONS
 Smoking cessation
 Nutrition maintenance:
- Assess radiation tolerability before starting radiation
- Plenty of fluids, frequent sips of cool liquids
- Disprin and local anesthetic gargles
- Avoid hot spicy, dry food
- Ryles tube insertion: Grade 3-4 dysphagia/ <1500kcal/day
 Respiratory physiotherapy: to improve pulmonary function
 During radiation, check patient status at least once a week
 Antiemetics, Antacids, soothening agents be prescribed when needed
Treatment interruptions or dose reductions for manageable acute
toxicities should be avoided.

73. THANK U

74. PHOTODYNAMIC THERAPY
PRINCIPLE:
- Uses photosensitiser (Hematoporphyrin) and red (WL=630nm) LASER
- Resultant free radicals destroy DNA of rapidly dividing cells.
INDICATIONS:
 Barrets esophagus
 Early esophageal cancer
 Persistant or recurrent esophageal cancer post RT, CCT, Sx
ADVERSE EFFECTS:
Local swelling and inflammation
Photosensitivity: shield skin and eyes for 4 hours

75. SURGERY

76. Resection should include
Lower esophagus to
a point above azygos
vein
Celiac lymph nodes
Left gastric lymph
nodes
Division of left gastric
artery
Proximal part of
stomach
Pyloroplasty