Ravi Shridhar, MD-PhD

1
Advanced Management of Esophageal Cancers A
Practical Approach
Radiation Oncology

• Ravi Shridhar, MD-PhD
• GI Radiation Oncology
• Moffitt Cancer Center
• Tampa, Florida

2
Topics For Discussion

• Workup
• Nutritional Support
• Multidisciplinary Treatment
• Radiation Dose/Technique
• Chemotherapy Regimen
• Surgery
• Adjuvant Treatment

3
Case

• 50 year old male with dysphagia that has
  progressed to solids and has experienced 30 pound
  weight loss in 3 months
• Patient goes to his local ER where endoscopy is
  performed revealing a partially obstructive mass
  at 35-40 cm from incisors in the background of
  Barretts
• Biopsies are taken and reveal moderate to poorly
  differentiated adenocarcinoma

Radiation Oncology
4
Question 1What is involved in the diagnostic
workup?
Radiation Oncology

1. CT chest, abdomen, pelvis
2. PET-CT
3. Endoscopic ultrasound (EUS) staging
4. Tissue for HER-2 status
5. A, B, and C
6. All of the above

5
Case

• EUS reveals a partially obstructive mass
  requiring a pediatric scope to bypass the
  stricture
• There is tumor invasion into the pleura
• 2 peritumoral lymph nodes (1 celiac node and 1
  esophageal node) are identified that are round
  and hypoechoic
• Self-expanding metal stent is placed but the
  patient is unable to tolerate secondary to pain

Radiation Oncology
6
Case

• CT chest-abdomen-pelvis reveal distal esophageal
  thickening and 3-4 cm celiac lymph node with no
  metastatic disease
• PET-CT scan reveal hypermetabolic mass (SUV 20)
  in the distal esophagus with 3 cm hypermetabolic
  celiac lymph node (SUV 9) with no evidence of
  metastatic disease
• HER-2 testing was positive (IHC 3)

Radiation Oncology
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Radiation Oncology
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Question 2Patient has 30 pound weight loss in 3
months and can only swallow liquids. Stent
placed but patient couldnt tolerate and was
removed. How would you manage?
Radiation Oncology

1. G-Tube
2. PEG Tube
3. Feeding Jejunostomy
4. Dophoff Tube
5. TPN

9
Case

• After discussion with the dietician, patient, and
  surgeon, patient underwent feeding jejunostomy
• Patients weight had stabilized.

Radiation Oncology
10
Question 3Final staging is T4N1M1a (6th ed) and
T4N2M0 (7th ed). What are your treatment
recommendations?
Radiation Oncology

1. Surgery /- adjuvant therapy
2. Preoperative chemotherapy
3. Preoperative radiotherapy
4. Preoperative chemoradiation
5. Definitive chemoradiation
6. Induction chemotherapy followed by preoperative
   chemoradiation

11
Case

• After discussion with the patient, medical
  oncologist, radiation oncologist, and surgeon, it
  was decided to proceed with preoperative
  chemoradiotherapy

Radiation Oncology
12
Question 4What chemotherapy regimen concurrent
with radiation should be used?
Radiation Oncology

1. 5-FU alone
2. Cisplatin and 5-FU
3. Oxaliplatin and 5-FU
4. Carboplatin and Taxol
5. Chemotherapy with Herceptin

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Question 5What radiation technique and dose
should be prescribed?
Radiation Oncology

1. 50 Gy using fluoroscopic barium esophagram
2. 41.4 Gy with 3D conformal (CT-based)
3. 41.4 Gy with IMRT (intensity modulated radiation
   therapy)
4. 50.4 Gy with 3D conformal
5. 50.4 Gy with IMRT
6. 50.4/56 Gy with dose-painting IMRT to regional
   lymphatics and tumor, respectively
7. 64.8 Gy with 3D conformal
8. 64.8 Gy with IMRT

14
Case

• Patient was treated with cisplatin (75 mg/m2 week
  1 and 5) and protracted venous infusion 5-FU (225
  mg/m2) days 1-5, 8-12, 15-19, 22-26, 29-33
• Radiation was delivered with dose-painting IMRT
  (50.4/56 Gy) using volumetric arc therapy (VMAT)
  and abdominal compression to reduce respiratory
  motion of the tumor
• Patient was seen weekly along with the dietician
  to monitor his nutritional status

Radiation Oncology
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Question 6When should the patient be restaged?
Radiation Oncology

1. 4 weeks
2. 6 weeks
3. 8 weeks
4. 10 weeks
5. 12 weeks

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Question 7What tests should be ordered?
Radiation Oncology

1. PET-CT, CT chest-abdomen
2. PET-CT
3. CT chest-abdomen
4. CT chest-abdomen and endoscopy
5. PET-CT, CT chest-abdomen, and endoscopy

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Case

• Patient underwent PET-CT and CT chest-abdomen 6
  weeks post-CRT
• Patient had a complete response on PET-CT
• CT TAP
• 1. Significant interval decrease in size of
  celiac axis lymph node, now 1 cm in short axis
  diameter.
• 2. Left lower lobe infectious or inflammatory
  infiltrate

Radiation Oncology
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Post CRT
Pre CRT
Radiation Oncology
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Case

• Endoscopy was not ordered
• But for the sake of argument, endoscopy was
  performed and biopsies were performed on the
  residual ulcer in the distal esophagus
• Biopsies were negative for malignancy

Radiation Oncology
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Question 8What would you recommend next?
Radiation Oncology

1. Observation with salvage surgery for local
   recurrence
2. Adjuvant chemotherapy
3. Endoscopic brachytherapy
4. Surgery

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Esophageal PET Response

• When comparing post-CRT PET with final pathology,
  PET could not consistently differentiate a path
  CR from pts who still had persistent disease
• Pts with a complete PET response after
  neoadjuvant therapy
• Sensitivity 61.8
• Specificity 43.8
• Positive predictive value 70
• Negative predictive value 35
• Accuracy 35

McLoughlin et al. J Am Coll Surg, 2008, 206(5)
879-886
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Esophageal EGD Response

• MSK study of 156 pt
• Negative endoscopic biopsy predicted for path CR
  in 31 of 118 pts
• Positive endoscopic biopsy predicted for
  pathologic residual disease in 95 38 pt

Sarkaria et al. Ann Surg, 2009, 249(5) 764-767
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Esophageal EGD Response

• 83 pts who completed CRT were evaluated with
  serial EGDs and biopsies
• Mean time to CR at the primary site was 97 days
  (range, 52-201 days)
• 4 pts, initial biopsy specimens found viable
  cancer cells within 75 days, subsequent
  examination found no such evidence, and the
  patients were thus designated as CR

Zenda et al. Dig Endosc. 2009 Oct21(4)245-51
24
Case

• Patient saw the surgeon and surgery was
  recommended
• Patient underwent pulmonary and cardiac clearance
  and then was scheduled for surgery

Radiation Oncology
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Question 9Who should not get surgery?

• A. BMI lt 18
• B. BMI 20
• C. BMI 25
• D. BMI 30
• E. BMI gt30

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Question 9Where should you refer the patient for
surgery?
Radiation Oncology

1. General surgeon at a hospital that performs lt10
   esophagectomies per year
2. Thoracic surgeon at a hospital that performs lt10
   esophagectomies per year
3. Thoracic surgeon at a hospital that performs gt30
   esophagectomies per year
4. Surgical oncologist at a hospital that performs
   gt30 esophagectomies per year

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Question 10Patient undergoes surgical resection.
What surgical technique should be recommended?
Radiation Oncology

1. Open transhiatal
2. Open transthoracic
3. Laparoscopic transhiatal
4. Laparoscopic transthoracic
5. 3-field approach
6. Robotic or minimally invasive transthoracic

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Case

• The following procedures were performed
• 1. Diagnostic laparoscopy.
• 2. Laparoscopic gastric mobilization.
• 3. Laparoscopic feeding jejunostomy.
• 4. Laparoscopic celiac lymphadenectomy.
• 5. Laparoscopic injection of the pylorus with
  Botox.
• 6. VATS.
• 7. A robotic-assisted Ivor Lewis
  esophagogastrectomy.
• 8. Periaortic lymphadenectomy.
• 9. Omental pedicle flap.
• Lysis of pleural adhesions.
• Patient had an episode of Afib
• Patient was discharged 10 days later

Radiation Oncology
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Case

• Final pathology
• 1 cm residual primary tumor
• 1/14 LN positive
• No LVSI or PNI
• All margins negative
• Final path was pT3N1M0
• Tumor regression score 1 (0 is a complete
  response)

Radiation Oncology
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Question 11How many lymph nodes should be
removed to be considered an adequate
lymphadenectomy?
Radiation Oncology

1. 8
2. 10
3. 12
4. 15
5. gt20

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Question 12What would you recommend for
adjuvant treatment?
Radiation Oncology

1. Herceptin for 1 year
2. Herceptin for 3 months
3. Chemotherapy with Herceptin
4. Herceptin and lapatinib
5. Chemotherapy for 3 months
6. Observation

32
Case

• Our team recommended observation
• Patient underwent serial restaging scans at 3
  months, 6 months, and 1 year
• 1 year restaging scans documented liver and lung
  nodules
• Biopsy was performed on a liver nodules and was
  positive for adenocarcinoma

Radiation Oncology
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Question 13Should you recheck HER-2 status
Radiation Oncology

1. Yes
2. No

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Question 14What chemotherapy regimen would you
recommend?
Radiation Oncology

1. ECF and Herceptin
2. DCF and Herceptin
3. Carbo-Taxol and Herceptin
4. Herceptin alone
5. Herceptin and lapatinib

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CaseSame patient only this time he is 80
without health issuesWould you offer surgery?
Radiation Oncology

1. Yes
2. No

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CaseSame patient (50 y old) only this time
patient refuses surgeryWhat would you recommend
after chemoradiation?
Radiation Oncology

1. 2 cycles of addition chemotherapy
2. 3 months of Herceptin
3. Restaging CT scan at 6 weeks, PET-CT and
   endoscopy at 12 weeks
4. Restaging CT scan and PET-CT at 6 weeks
5. PET-CT and endoscopy at 6 weeks

37
Case

• CT chest abdomen at 6 weeks was negative for
  metastatic disease
• PET-CT at 12 weeks showed no evidence of
  hypermetabolic activity
• Endoscopy at 12 weeks revealed an ulcer.
  Biopsies were taken and revealed residual
  adenocarcinoma

Radiation Oncology
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CaseHow would you manage residual cancer?
Radiation Oncology

1. More chemotherapy
2. Surgery
3. EMR
4. More chemoradiation
5. Endoscopic brachytherapy

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Variable Levels No Surgery () Surgery () P value
Median Age (y) (range) 69.5 (40.1 93.1) 63.4 (29.6 81.5) lt0.0001
Gender Female 6 (9.0) 9 (9.6) 1.000
Gender Male 61 (91.0) 85 (90.4) 1.000
T-Stage (6th ed) 1 15 (22.7) 5 (5.3) 0.0016
T-Stage (6th ed) 2 10 (15.2) 11 (11.7) 0.0016
T-Stage (6th ed) 3 28 (42.4) 64 (68.1) 0.0016
T-Stage (6th ed) 4 13 (19.7) 14 (14.9) 0.0016
N-Stage (6th ed) 0 10 (15.2) 14 (14.9) 1.000
N-Stage (6th ed) 1 56 (84.8) 80 (85.1) 1.000
M-Stage (6th ed) 0 58 (86.6) 73 (77.7) 0.2176
M-Stage (6th ed) 1a 9 (13.4) 21 (22.3) 0.2176
AJCC Stage (6th ed) I 4 (6.0) 0 (0.0) 0.0093
AJCC Stage (6th ed) IIA 6 (9.0) 12 (12.8) 0.0093
AJCC Stage (6th ed) IIB 18 (26.9) 12 (12.8) 0.0093
AJCC Stage (6th ed) III 30 (44.8) 49 (52.1) 0.0093
AJCC Stage (6th ed) IVA 9 (13.4) 21 (22.3) 0.0093
Tumor Length lt5 cm 47 (70.1) 63 (67.0) 0.7346
Tumor Length gt5 cm 20 (29.9) 31 (33.0) 0.7346
RT Technique 3DCRT 25 (37.3) 34 (36.2) 1.000
RT Technique IMRT 42 (62.7) 60 (63.8) 1.000
RT Dose (Gy) lt50.4 39 (58.2) 65 (69.1) 0.1771
RT Dose (Gy) gt50.4 28 (41.8) 29 (30.9) 0.1771
Tumor Location Upper 1 (1.5) 0 (0.0) 0.3129
Tumor Location Middle 1 (1.5) 4 (4.3) 0.3129
Tumor Location Distal 38 (56.7) 45 (47.9) 0.3129
Tumor Location GEJ 27 (40.3) 45 (47.9) 0.3129
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(No Transcript)
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Overall Survival Overall Survival Overall Survival Overall Survival
Variable Hazard Ratio 95 CI p-value
Age 1.020 0.999 1.042 0.0612
Gender (vs. Male) 2.329 1.084 5.007 0.0303
Stage (vs. III/IVA) 0.384 0.205 0.718 0.0028
Tumor Length (vs. lt5 cm) 0.487 0.294 0.807 0.0053
RT Dose (vs. lt50.4 Gy) 0.927 0.552 1.558 0.7752
RT Technique (vs. 3DCRT) 0.782 0.456 1.341 0.3708
Surgery (vs. No) 0.417 0.251 0.693 0.0007
Tumor Location (vs. Distal) Middle GEJ 0.128 0.937 0.014 1.143 0.569 1.543 0.0657 0.7989
Induction Chemo (vs. No) 0.718 0.343 1.502 0.3791
42
CaseIf biopsies were negative would you
recommend surveillance and treatment for the
Barretts esophagus
Radiation Oncology

1. Yes
2. No

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CRT and Barretts Esophagus

• 43 pts treated with CRT for esoph AC with
  Barretts (BE)
• BE persisted after CRT in 93 (40/43)
• 27 pts were resected. BE was detected in all
  surgical specimens (100)
• In 59 (16/27) cases, there was path CR in the
  tumor

Barthel JS et al. Gastrointest Endos, 2010,
71(2)235-240
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CRT and Barretts Esophagus

• Persistent BE was identified in 88 (14/16) of
  cases not resected
• The mean length of BE before and after CRT was
  6.6 cm and 5.8 cm, (P 0.38)
• Conclusion
• If no surgery planned, then patient must have BE
  ablated (EMR, RFA, Cryo) and continue routine
  surveillance
• BE after CRT is still prone to cancer
  transformation

Barthel JS et al. Gastrointest Endos, 2010,
71(2)235-240