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ESMO SUMMIT MIDDLE EAST 2018Clinical Case Presentation
Shailesh V. Shrikhande, MS, MD, FRCS (Hon)
Chief, GI and HPB Surgery
Professor & HOD Surgical Oncology
Tata Memorial Centre, Mumbai, India
6-7 April 2018, Dubai, UAE
CONFLICT OF INTEREST DISCLOSURE
Honorarium received by Tata Memorial Hospital
Covidien, IRCAD Meeting 2016, Taiwan
Johnson & Johnson, Gastric Advisory Council 2015, Seoul, Korea
Merck Serono, Asia Pacific mCRC Meeting 2015, Singapore
EXPERT PANEL
Josep Tabernero, Medical Oncologist
Marwan Ghosn, Medical Oncologist
Syed M. Hasnain, Radiation Oncologist
Mohsen Mokhtar, Medical Oncologist
Eric Van Cutsem, Medical Oncologist
Fortunato Ciardiello, Medical Oncologist
CASE 1: HISTORY (OCTOBER 2016)
50 year old gentleman
Diabetic on Rx – 5 yrs
Presented with abdominal pain – 1 month
H/o 10 kg LOW – over 3 months
Clinical examination
Vitals stable, no icterus
ECOG 1
PA - large palpable mass 8x6 cm in Right hypochondrium
PR - no growth
EVALUATION
USG abdomen and pelvis:
Large GB mass infiltrating liver
Hb: 16 gm%
Liver Functions:
Bilirubin 0.5 mg%
Albumin 4.3 mg%
Liver Enzymes - WNL
ROLE OF TUMOR MARKERS?
S. CA 19.9 : 44960.0 units
S. CEA: 169.71 units
TUMOR MARKERS
CEA: Specificity 90%; Sensitivity only 50% when used for screening
CA 19-9: Sensitivity and specificity 75%
Minimal clinical value compared with clinical awareness but useful for follow up
NEXT MODE OF EVALUATION?
A. Contrast enhanced CT scan
B. MRI
C. PET
INVESTIGATIONS
CECT abdomen (October 2016)
Large enhancing lesion involving GB & extending into liver seg IVa, IVb & V
Loss of fat plane with hepatic flexure of colon
Multiple portal & portocaval nodes largest 1.7 X 1.5cm
Solitary pulmonary millimetric nodule in right upper lobe ant seg - indeterminate
ROLE OF PET SCAN?
LOF plane with duodenum and
colon
Enhancing mass lesion in
relation to GB fossa
Peripherally Enhancing lesion Central necrosis
PET CT (25.11.2016)
Peripherally enhancing centrally necrotic bulky soft tissue mass measuring 6.9 x
6.1 x 7.3 cm is noted in the right lobe of liver
Loss of fat planes with hepatic flexure and duodenum with perilesional nodules
GB cannot be differentiated separately from the mass
Low grade FDG avid peripancreatic and portocaval nodes are noted measuring 9
mm with a max SUV of 6.52
ROLE OF STAGING LAPAROSCOPY?
A. YES
B. NO
STAGING LAPAROSCOPY
Most CA GB patients do not require palliative operations, and incidence of
occult metastatic disease is high and hence staging laparoscopy makes
sense
Yield is as high as 48% (Weber et al, 2002)
Even in patients who had prior simple cholecystectomy, yield is as high as
20% and is indicated
STAGING LAPAROSCOPY (16.11.2016)
No evidence of peritoneal / omental liver metastases
Hepatic flexure of colon and duodenum adherent to GB; no frank infiltration
MANAGEMENT PLAN ?
A. Radical Curative Surgery
B. Neoadjuvant chemotherapy and reassess for Surgery
C. Neoadjuvant chemoradiotherapy and reassess for Surgery
D. Palliative treatment options
DO WE NEED A BIOPSY?
USG guided GB mass (03.11.2016)
Moderately differentiated adenocarcinoma
ROLE OF CHEMOTHERAPY AND RADIOTHERAPY IN
GB CANCERS
Is there any strong evidence or recommendation ?
Should we routinely use neoadjuvant treatment in Ca GB ?
What are the indications for neoadjuvant treatment?
ON-GOING TRIAL AT TATA MEMORIAL
In POLCA-GB trial - CTRT arm (NCT02867865)
Received EBRT to GB tumor mass to a dose of 52Gy/25#/35 days - SIB technique
Remaining PTV 45gy/25# using 6MV photons with Intensity Modulated Arc technique from
6/12/16 to 9/1/17
Along with 5 cycles of concurrent Gemcitabine on 06-12-2016, 13-12-2016, 20-12-2016, 27-
12-2016 and 03-01-2017.
Received 2# Gem - Cis (LD 21.2.2017)
CT Abdomen (14.03.2017)
Residual lesion in GB fossa with liver infiltration- SD
Episode of hematemesis on 9th March at home
UGI Endoscopy (11.03.2017)
Acute ulcer in the bulb of duodenum
UGIE (07/04/17)
Diffuse erythema in antro-pyloric region
Small superficial ulcer 0.5 x 0.5 with clean base in pre-pyloric region
Duodenum: D1 and D1-D2 junction showed infiltrated mucosa and erythema.
D2-Normal. No active bleeding.
Response assessment PET (12/04/2017)
Significant decrease in the size and metabolic activity of the GB fossa mass and LN with
residual viable disease; Metabolic activity of Right SCF node
Right SCF FNAC
Necrotizing granulomatous inflammation, suggestive of tuberculosis.
Malignant cells not seen
FURTHER PLAN?
A. Continue chemotherapy
B. Assess for Surgery
Started on ATT (April 2017)
After 1 month of ATT posted for Surgery
Plan:
Radical Cholecystectomy with Distal Gastrectomy
Underwent Radical Cholecystectomy with Distal Gastrectomy, D1 resection with
ante-colic Gastro-jejunostomy on 12.05.17
Intraoperative findings
➢GB mass fistulized in D1
➢No colonic involvement
➢Peri-portal and porto-caval nodes
➢Inter-aortocaval nodes negative on FS
Recovered uneventfully except for serous discharge with prolonged drain for 2 weeks
HISTOPATHOLOGY
No residual viable tumor
Cystic duct margin: free of tumor
Gastric and duodenal margin: free of tumor
Lymph nodes: 6 negative nodes
ADJUVANT TREATMENT
3# Gemcitabin + Cisplatin
ABC 02 TRIAL
ADJUVANT CAPECITABINE FOR BILIARY TRACT CANCER:
THE BILCAP RANDOMIZED STUDY.
Conclusion:
Cape improves OS in BTC when used as adjuvant and should become standard of care.
FOLLOW UP
Asymptomatic at last follow up
Normal tumor markers
USG A+P: No e/o disease
Future Oncology 2015
HPB 2018 (ARTICLE IN PRESS)
CHAUDHARI V, SHRIKHANDE SV, GOEL M ET AL.
OUTCOME OF NEOADJUVANT CHEMOTHERAPY IN “LOCALLY ADVANCED/BORDERLINE
RESECTABLE” GALLBLADDER CANCER: THE NEED TO DEFINE INDICATIONS.
Proposes clinico-radiologic criteria to define borderline resectable / locally advanced GBC
160 consecutive patients (2010 to 2016)
Chemotherapy with neoadjuvant intent in locally advanced/borderline resectable GBC showed
good response rates (clinical benefit rate 70%)
Curative surgical resection or disease stabilisation in significant number of patients (66/160)
Definitive surgery after favourable response to NACT results in good survival.
TATA MEMORIAL HOSPITAL CRITERIA FOR BR / LA GBC • TUMOUR
• (T3-T4 tumours)
• Contiguous Liver involvement > 2cm
• Involvement of bile duct causing obstructive jaundice
• (Type I/II block on MRCP/ERCP/PTBD)
• Radiological / Endoscopic involvement of antropyloric region of stomach, duodenum, hepatic flexure of colon or small intestine
• NODE
• (N1 station)
• Radiological suspicion of lymph node involvement N1 - Hepatic artery (Station 8), Hepatoduodenal ligament (Station12), Retro
pancreatic / retroduodenal (Station 13)
• Size > 1cm in short axis, round in shape, and heterogenous enhancement on CT/PET scan.
• VASCULAR
• (T4 tumours)
• Impingement/ involvement (<180-degree angle) of one or more of the following blood vessels:
• Common Hepatic Artery and Right & Left Hepatic artery
• Main Portal vein and Right & Left Portal vein
• FOR INCIDENTAL GBC
• Residual/Recurrent mass in GB fossa /liver bed
• N1 nodes as per nodal criteria.
• Involvement of bile duct causing OJ (Type I/II Block)
CASE 2: HISTORY
62 year / Male / ECOG 1
Recently diagnosed diabetic
Presented with abdominal pain 2 months
O/E
GC: Good
No Pallor / Icterus / SCLN
PA: Soft, no mass
INVESTIGATIONS
Liver Function Tests
Bilirubin 0.8 mg%
Albumin 4.4 mg%
AST/ALT 14 / 15
Hb: 14.6 gm%
USG abdomen: Pancreatic mass
ROLE OF TUMOR MARKERS IN PANCREATIC CANCER
CEA: 7.5 units
CA 19-9: 911 units
NEXT MODE OF EVALUATION
A. Contrast enhanced CT scan (CECT)
B. MRI
C. PET
D. EUS
MDCT PANCREATIC PROTOCOL, NCCN (2016)
Hypodense mass at
pancreatic neck
Collaterals at
SMV-SV junction
SMV-SV
confluence
involved
Hypodense
mass at neck
of pancreas
Distal SMV stump
available for
reconstruction
MDCT (08.08.2016)
Hypodense mass 2.6 x 2.6 cm at pancreatic neck
Encasing distal most part of SMV and proximal 9 mm of PV near the confluence,
with significant luminal narrowing
Portal vein mildly dilated (15 mm at Porta), few dilated portosystemic collaterals,
Splenic vein not encased
The lesion abuts the common hepatic artery and SMA
No significant LN, no distant metastases
ROLE OF STAGING LAPAROSCOPY?
A. Yes
B. No
Indications
CA 19-9 > 1000
Pancreatic body mass > 4 cm
ROLE OF BIOPSY
EUS guided biopsy?
USG guided FNAC
Adenocarcinoma
WITH THIS INFORMATION….
Is it,
A. Resectable?
B. BRPC?
C. LAPC?
With regard to the porto-venous axis, any degree of
involvement falls into the category of borderline resectable
disease as long as the vein can be technically resected and
reconstructed
BRPC: MANAGEMENT PLAN?
A. Upfront Surgery
B. NACT and reassess for Surgery
C. NACT/RT and reassess for Surgery
BORDERLINE RESECTABLE:
NACT VS NACT/RT, RESULT OF 3 META-ANALYSIS
Neoadjuvant Therapy in BRPC: Systematic Review and Meta-Analysis
63% pts resected
87% R0
Median OS 25.9 months (resected)
FOLFIRINOX
(n=64)
Gem-based
Resection
rate
72% 67%
R0 60% 58%
G3 /4 Toxicity 53% 30%
Tang K. Pancreatology 2016;16: 28-37
Toxicity
Grade 3 & 4 toxicity 37.3%
Tang K. Pancreatology 2016;16: 28-37
Plan:
NACT and reassess
Received 4# FOLFIRINOX
POST NACT: REASSESSMENT
CECT Scan
• Partial Response
• SMV appears encased up to 2.3 cm near portal
confluence
• Splenic vein encased near confluence up to
length of 1.6 cm
• Main PV appears partially encased for 2 cm
Disease at neck
with SMV SV
junction involved
S. CA 19.9 611 units
S. CEA 6.75 units
PLAN : Pylorus preserving / Classical pancreaticosplenectomy with portal
vein confluence resection with SOS PTFE Graft reconstruction (28.12.16)
INTRAOPERATIVE FINDINGS
Tumor involving the head, neck and body of pancreas
Encasement of the PV, SMV and the SMV - PV junction
The SMA adventitia was involved and was resected from the SMA
No omental, peritoneal or liver deposits.
PANCREATIC HEAD, NECK AND BODY WAS INVOLVED
SMV looped
RADICAL TOTAL PANCREATECTOMY SPECIMEN
ISGPS, TYPE III PORTAL VEIN RESECTION
POSTOPERATIVE TUMOR BED
HPR: CAN YOU ELABORATE ON IMPORTANCE OF EACH AS
PROGNOSTICATION ?
WHAT IS ADEQUATE LYMPHADENECTOMY IN CA PANCREAS ?
ROLE OF EXTENDED RESECTIONS IN CA PANCREAS ?
IS THERE ANY ROLE OF ARTERIAL RESECTIONS ?
MDAC; ypT3N0
LVI +
PNI+
Retroperitoneal/SMA surface involved
0/24 Nodes
Post op period:
Uneventful recovery
Received 6# single agent Gemcitabine
FOLLOW UP
Developed B/L multiple liver metastases recently
• In the intention-to-treat analysis, the 1-YSR and 2-YSR in the neoadjuvant treatment group
(74% and 41%) were nearly twice as high as in the upfront surgery group (48% and 26%)
• In the PP1 and PP2 analysis, there was no difference in the 2-YSR between the groups
Jang J, et al. Ann Surg 2018
In 44% of pCR patients, no recurrence or death was observed.
Median OS 27 months; in pCR group median OS
was not yet met at 60 months; patients without a
pCR 26 months
pCR , a negative lymph node status
and neodjuvant FOLFIRINOX
independent predictors of OS
He J, et al. Ann Surg 2018