Anatomy to management Ca Esophagus and GE junction

2. Challenges !!!

9. Know the Expectations/interests/willingness to
learn…
and …

11. Background
• 6th most common cause of cancer deaths worldwide.
• The principal histologic types: are sq cell ca. & adenoca.
• Squamous cells line the entire esophagus, so SCC can occur in any
part of the esophagus, but it often arises in the upper half.
• Adenocarcinoma typically develops in specialized intestinal
metaplasia (Barrett metaplasia) that develops as a result of
gastroesophageal reflux disease (GERD); typically arises in the
lower half of the distal esophagus and often involves the
esophagogastric junction(GEJ).

12. GERD WITH BARRETT
METAPLASIA
Patients with Barrett
esophagus have a 30 to 60
times greater risk of
developing
adenocarcinoma of the
esophagus than the
general population!!!

15. Treatment history and controversy
• Surgery has traditionally been the treatment for esophageal
carcinoma.
• Current guidelines recommend – surgery ( resection or
esophagectomy), depending on the stage.
• Nonoperative therapy is usually reserved for patients who
are not candidates for surgery because of clinical conditions
or advanced disease.

16. Anatomy

17. • A long muscular tube connecting
the
pharynx to the stomach
• Extends from C6 to T11 vertebra
• Length: approximately 25 cm
• Diameter: approximately 2 cm
when relaxed

19. LAYERS OF ESOPHAGEAL WALL

20. • Esophageal branches of
inferior thyroid artery (upper
third)
• Esophageal branches of
thoracic part of
aorta (middle third)
• Esophageal branches of left
gastric artery (lower third)
Arterial
supply

21. • The cervical esophagus drains into the
internal jugular and upper tracheal
lymph node groups.
• The thoracic esophagus drains into the
superior, middle, lower mediastinal
lymph node groups, and into the
abdominal segment
• However, extensive communication
among the lymphatics results in a
varied and unpredictable nodal
involvement pattern
LYMPHATIC
DRAINAGE

22. Nodal Skip metastasis (NSM)

23. Mechanism of skip nodal metastasis
• When tumor cells penetrate the esophageal wall through
longitudinal drainage ducts and subsequently traverse
transverse drainage ducts, there is a higher possibility of
bypassing lymph nodes near the primary tumor and
metastasizing to more distant lymph nodes, promoting the
development of lymph node skip metastasis .
• Furthermore, a Japanese study found that lymphatic skip
metastasis in thoracic esophageal carcinoma was associated
with the absence of lymphatic vessels between the middle
mediastinum and supraclavicular muscles.

24. RISK FACTORS
• Smoking and alcohol use- Sq. cell ca
• Dietary associations- Foods products containing N-nitroso
compounds increase the risk of esophageal SCC.
• Red meat consumption increases the risk
• Low dietary folate intake is associated with an increased risk of
esophageal SCC.
• Higher intake of fruits and vegetables reduces the risk of esophageal
SCC.
• High body mass index,
• GERD, and resultant Barrett esophagus

25. Clinical presentation
• Dysphagia- the most common presenting symptom of esophageal cancer
(initially for solids but eventually progresses to include liquids).
• Weight loss
• Bleeding
• Pain
• Hoarseness - This is caused by invasion of the recurrent laryngeal nerve;
• Respiratory symptoms (persistent cough and recurrent pneumonia) – due
to aspiration/TOF

26. Differential Diagnoses of dysphagia

28. WORKUP

32. American Joint Committee on Cancer (AJCC)
TNM Staging Classification for Carcinoma of the
Esophagus and Esophagogastric Junction (8th ed.,
2017)
Squamous Cell Carcinoma and Adenocarcinoma

33. STOMACH CANCER OESOPHAGEAL CANCER

34. cTNM , pTNM , ypTNM
• cTNM: Newly diagnosed, not-yet-treated patients,
• pTNM: Patients undergoing resection without prior treatment,
• ypTNM: Patients receiving preoperative therapy),post neoadjuvant
pathologic staging

35. Mucosa
Esophagus lumen
Adventitia

36. •EUS(Endoscopic ultrasonogaphy) performed prior to any
treatment is important in the initial clinical staging of
neoplastic disease.
•Ultrasound images provides evidence of depth of tumor
invasion (T ), presence of abnormal or enlarged lymph
nodes (N)

38. TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis- High-grade dysplasia, defined as malignant cells confined to the
epithelium by the basement membrane
T1- Tumor invades the lamina propria, muscularis mucosae, or
submucosa
T1a Tumor invades the lamina propria or muscularis mucosae
T1b Tumor invades the submucosa
T2- Tumor invades the muscularis propria
T3- Tumor invades adventitia
T4- Tumor invades adjacent structures
T4a Tumor invades the pleura, pericardium, azygos vein, diaphragm,
or peritoneum
T4b Tumor invades other adjacent structures, such as the aorta,
vertebral body, or airway
T Primary Tumor

39. N (Regional Lymph Nodes)
NX- Regional lymph nodes cannot be assessed
N0- No regional lymph node metastasis
N1- Metastasis in one or two regional lymph nodes
N2- Metastasis in three to six regional lymph nodes
N3- Metastasis in seven or more regional lymph nodes

40. -Surgical pathology yields the most accurate staging
-EUS (Endoscopic ultrasound)
-CT SCAN , and
-FDG-PET/CT (18-fluorodeoxyglucose) have greatly
improved the accuracy of clinical staging.

41. Imaging Studies

42. • CT scan
• PET scan
• Endoscopic ultrasound (EUS)- Only method capable of
delineating the layers of the esophageal wall
• Bronchoscopy
• Barium swallow

43. Barium swallow
• Barium swallow is
performed as the initial test.
• The patient swallows barium
rapidly and the esophagus is
imaged using x-rays.
• A confirmatory finding of
esophageal cancer with
barium swallow includes:
• Tapering stricture known
as a “Rat's tail"

44. While contrast-enhanced CT is the most widely used
modality for detecting distant metastases in esophageal
cancer, FDG-PET/CT is more sensitive than CT alone for
staging cM disease.
The addition of FDG-PET improves the detection of distant
metastases that may remain occult on CT scan of the chest
and abdomen, there by allowing proper patient selection
for surgical resection

46. TREATMENT OPTIONS
Surgery
Radiotherapy
Chemotherapy

47. Resectable esophageal or GEJ cancer:
• T1a tumors: EMR + ablation
• T1b: Esophagectomy in tumors in the submucosa or deeper may be
treated with esophagectomy.
• T1–T3: Tumors are resectable even with regional nodal metastases
(N+), multi-station lymphatic involvement is a relative
contraindication to surgery,
• T4a: Tumors with involvement of pericardium, pleura, or diaphragm
are resectable.

48. ENDOSCOPIC MUCOSAL RESECTION ( EMR )

49. Siewert Classification
• Siewert tumor type should be assessed in-
All patients with
adenocarcinomas involving
the EGJ.
• Siewert Type I: Tumor Epicenter
located within 1 cm to 5 cm above
the anatomic EGJ.
• Siewert Type II: Tumor epicenter
within 1 cm above and 2 cm below
the EGJ.
• Siewert Type III: Tumor epicenter
between 2 cm and 5 cm below the
EGJ, which infiltrates the EGJ and
lower esophagus from below.

50. Siewert Classification for Adenocarcinomas involving the GEJ
[Based on anatomic location of epicentre of the tumor]

51. Unresectable esophageal cancer
• cT4b tumors
• Patients with EGJ with supraclavicular lymph node involvement
• Distant metastases

52. Acceptable operative approaches for resectable esophageal or EGJ
cancer
• Ivor Lewis esophagogastrectomy (laparotomy + right thoracotomy)
• McKeown esophagogastrectomy (right thoracotomy + laparotomy
+ cervical anastomosis)
• Transhiatal esophagogastrectomy (laparotomy + cervical
anastomosis)
• Robotic minimally invasive esophagogastrectomy

53. Ivor Lewis Esophagectomy OR (GASTRIC PULL UP)
MID/DISTA
L LESION
Acceptable
conduits:
Gastric (preferred)
Colon
Jejunum

55. •In patients undergoing esophagectomy without induction
chemoradiation, at least 15 lymph nodes should be
removed and assessed to achieve adequate nodal staging.
•The optimum number of nodes after preoperative
chemoradiation is unknown, although similar lymph node
resection is recommended

56. PRINCIPLES OF SYSTEMIC THERAPY

57. Systemic therapy regimens recommended for :
Advanced esophageal adenocarcinoma,
EGJ adenocarcinoma, and
Gastric adenocarcinoma
[may be used interchangeably]
(except as indicated)

58. PRINCIPLES OF SYSTEMIC THERAPY
Trastuzumab should be added to first-line
chemotherapy for advanced HER2 overexpression
positive adenocarcinoma.

59. PRINCIPLES OF RADIATION THERAPY

60. [Radiation therapy (preoperative, postoperative, or
palliative) can be an integral part of treatment for
esophageal and EGJ cancers]
• In general, Siewert I and II tumors should be managed with radiation therapy
guidelines applicable to esophageal and EGJ cancers.
• Siewert III tumors patients may receive perioperative chemotherapy or
preoperative chemoradiation depending on institutional preference, and are
generally more appropriately managed with radiation according to guidelines
applicable to gastric cancers.
• These recommendations may be modified depending on the location of the
bulk of the tumor

61. RT Dosing schedule
• Preoperative RT: 41.4–50.4 Gy
• Postoperative RT: 45–50.4 Gy
• Definitive RT: 50–50.4 Gy
• All RT doses should be delivered in fractions of 1.8 to 2 Gy per day.
• There is no evidence from randomized trials to support the
additional benefit of higher dose range
HIGHER DOSE ADVANTAGE ??

62. Decision making !!!
Multidisciplinary
Tumor board (MDT)

63. CROSS FLOT 4 MACDONALD
SANO
MAGIC POET

64. ChemoRadiotherapy for Oesophageal
cancer followed by Surgery Study
- CROSS TRIAL
Standard of care for patients with locally
advanced resectable esophageal or
esophgogastric junctional cancer.
?

66. METHODS
Randomly assigned patients with resectable tumors to
receive surgery alone or weekly administration of
Paclitaxel 50 mg/m2 IV over 1 hours followed by
Carboplatin AUC 5 IV over 30 minutes , for 5
weeks with concurrent radiotherapy
(41.4 Gy in 23 fractions, 5 days per week), followed by
surgery.

67. Conclusion
Preoperative chemoradiation is associated with improved OS,
DFS, and pCR compared with preoperative chemotherapy or
surgery alone in patients with locoregional esophageal cancer.
-The R0 resection rate was also higher in PREOP CHEMORT
- Preoperative chemoradiation significantly reduced locoregional
recurrence

68. MAGIC
FLOT 4
Perioperative
Chemotherapy

69. MAGIC TRIAL

70. ( 3 ECF SURGERY 3 ECF )
In resectable adenocarcinoma of the stomach, esophagogastric junction,
or lower esophagus to either perioperative chemotherapy and surgery or
surgery alone.
Chemotherapy consisted of three preoperative and three postoperative
cycles of intravenous
Epirubicin 50 mg/m2 and
Cisplatin 60 mg/m2 )on day 1, and a continuous intravenous infusion of
Fluorouracil (200 mg/m2 per day) for 21 days.
The primary end point was overall survival.

71. MAGIC (Medical Research Council Adjuvant Gastric
Infusional Chemotherapy)
CONCLUSIONS:
In patients with operable gastric or lower esophageal
adenocarcinomas, a perioperative regimen of ECF decreased tumor
size and stage and significantly improved progression-free and
overall survival

72. FLOT 4 ( IN GASTRIC AND EGJ ADENOCA)

74. 4 preoperative and 4 postoperative cycles of
Docetaxel 50 mg/m2,
Oxaliplatin 85 mg/m,2
Leucovorin 200 mg/m,2
Fluorouracil 2600 mg/m2 as 24-h infusion on day 1
q 2-weekly cycles

75. Conclusion
Periop FLOT improved outcome in patients with
resectable gastric and GEJ cancer compared to
periop ECF/ECX.

76. Macdonald

78. CONCLUSIONS
Postoperative chemoradiotherapy should be considered for
all patients at high risk for recurrence of adenocarcinoma of
the stomach or gastroesophageal junction who have
undergone curative resection.

79. PreOperative therapy in Esophagogastric
adenocarcinoma Trial (POET)
Patients and methods:
Patients with locally advanced
adenocarcinomas of the
oesophagogastric junction (Siewert
types I–III) were eligible.
Randomisation was done to
Group A: Induction
chemotherapy followed by surgery
and
Group B: chemoradiotherapy followed
by surgery.

80. Conclusion
Long-term follow-up data suggest a benefit in local
progression-free survival when radiotherapy was added
to preoperative chemotherapy in patients with locally
advanced adenocarcinoma of the oesophagogastric junction.
The POET was the first randomised controlled phase III study
to compare induction chemotherapy with induction
chemoradiotherapy (CRT) followed by surgery

81. SANO Trial …
• The Surgery As Needed for Oesophageal cancer (SANO) trial
compares active surveillance with standard oesophagectomy
for patients with a clinically complete response (cCR) to
neoadjuvant chemoradiotherapy.
• Organ preservation approch

83. Method
• A total of 300 patients with clinically complete response
(cCR, i.e. no local or disseminated disease proven by
histology) after nCRT will be randomised to show non-
inferiority of active surveillance to standard
oesophagectomy

84. Findings from the SANO trial also reported clinically
complete responses after neoadjuvant
chemoradiotherapy.
Active surveillance after neoadjuvant
chemoradiotherapy may be an alternative to surgery for
some patients with oesophageal cancer, as suggested
by encouraging data from the SANO trial presented at
the ESMO Congress 2023 (Madrid, 20–24 October)
(LBA75).

85. Definitive Chemoradiation Therapy

86. -Definitive chemoradiation is preferred for all T4b (unresectable)
tumors.
Resulted in superior OS, disease-specific survival,
locoregional control, and palliation in patients with
unresectable esophageal cancer.
Inj Paclitaxel 50 mg/m2 over 1 hour followed by
Inj Carboplatin AUC 2 IV over 30 minutes ,
repeat weekly for 5 weeks with radiation
( Definitive RT: 50Gy/25#)

87. PRINCIPLES OF SURGERY
• Cervical or cervicothoracic esophageal
carcinomas (<5 cm from the
cricopharyngeus) should be treated
with definitive chemoradiation
• Esophageal resection should be
considered for all patients who are
physiologically fit with resectable
esophageal cancer (>5 cm from
cricopharyngeus).

88. DEFINITIVE
CHEMORADIATION
SURGERY ALONE,
WITH RADIOTHERAPY
OR
WITH CHEMOTHERAPY
OR
CHEMO RT WITHOUT SURGERY
CRICOPHARYNGEAL
SPHINCTER

89. Preoperative chemoradiation is the preferred
approach for localized adenocarcinoma of the
thoracic esophagus or EGJ.
Perioperative systemic therapy is an alternative option for
distal esophagus and EGJ.

90. Postoperative Systemic Therapy
Preferred Regimen:
Nivolumab only after preoperative chemoradiation with
residual disease (category 1),
Day 1: Nivolumab 240mg IV over 30 minutes
Repeat cycle every 2 weeks for 8 cycles, followed by:
Day 1: Nivolumab 480mg IV over 30 minutes.
Repeat cycle every 4 weeks for 9 cycles or until maximum
duration of 1 year.

91. Systemic therapy for unresectable, locally
advanced, recurrent or metastatic disease
(where locally therapy is not indicated)

94. Trastuzumab- ToGA trial
• The ToGA trial was the first randomized prospective phase III
trial that evaluated the efficacy and safety of trastuzumab in
HER2 overexpression positive advanced gastric and EGJ
adenocarcinoma.
• This study established trastuzumab in combination with
cisplatin and a fluoropyrimidine as the standard treatment
for patients with HER2 overexpression positive advanced
gastroesophageal adenocarcinoma.

95. ROLE OF BRACHYTHERAPY IN CARCINOMA
ESOPHAGUS (ILRT )

96. Intraluminal brachytherapy ( ILRT )

99. Methods:
We undertook a review of the available literature and techniques
developed in the past three decades to emphasise the role of
brachytherapy in curative or palliative settings in the treatment of
oesophageal carcinoma.

100. Important point…
• Brachytherapy permits delivery of high tumouricidal doses to superficial
cancerous growth of the oesophagus
• Mostly given in combination with external beam radiation in patients with
poor performance scores not likely to tolerate an aggressive chemoradiation
regimen or as a boost to concurrent chemoradiotherapy.
• It is very effective in terms of local tumour control as well as in relieving
symptoms in advanced/recurrent disease.
• Despite the inherent radio sensitivity of oesophageal tumours, curative doses
are difficult to achieve because of close proximity of the target to vital
organs.

101. • It can be used in definitive, adjuvant or palliative settings.
Definitive indications of ILRT are superficial tumour (T1) with
curative intent where it can be used as the sole treatment modality.
In adjuvant settings, ILRT can be used in combination with EBRT to
boost the primary disease.
• If the tumour remission achieved by EBRT has not been sufficient
or in patients with the local recurrence, ILRT can be given with the
hope to increase the local effect.

102. ILRT in adjuvant settings
Good candidates:
-Unifocal primary tumour ≤ 10
cm in length,
-tumour confined to
oesophageal wall,
-mid-thoracic location and
- no evidence of intra-abdominal
or metastatic disease.
Poor candidates:
-extra oesophageal extension,
-tumour >10 cm in length,
-regional nodal involvement or
- tumour involving
gastrooesophageal junction or
cardia.

104. Majority of the patients suffer from acute oesophagitis, confirmed
by oesophagoscopy; however, perforation and bleeding are rare.
• Long-term side effects :(occur after radical combination treatment).
-chronic oesophagitis,
-ulceration(up to 30%),
-stenosis/stricture (5–30%) and
-fistula (5–10%)
• RTOG 9207 reported life-threatening toxicity or treatment-related deaths in
24 and 10% cases, respectively.
• Treatment-related oesophageal fistulas occurred in 12% of patients when
brachytherapy was used as a boost.

105. Less commonly used due to-
High expertise requirement,
Lack of established evidence,
Risk of life-threatening complications and
Lack of interest in brachytherapy.
But still it remains an attractive option due to superior
dosimetry which may result in high therapeutic ratio. It offers
quick and useful palliation for a prolonged period, along with
the good quality of life