ESMO SUMMIT MIDDLE EAST 2018

Transcription

1 ESMO SUMMIT MIDDLE EAST 2018 Clinical 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

2 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

3 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

4 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

5 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

6 ROLE OF TUMOR MARKERS? S. CA 19.9 : units S. CEA: units

7 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

8 NEXT MODE OF EVALUATION? A. Contrast enhanced CT scan B. MRI C. PET

9 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

10 ROLE OF PET SCAN?

11 Enhancing mass lesion in relation to GB fossa LOF plane with duodenum and colon Peripherally Enhancing lesion Central necrosis

12 PET CT ( ) 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

13 ROLE OF STAGING LAPAROSCOPY? A. YES B. NO

14 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

15 STAGING LAPAROSCOPY ( ) No evidence of peritoneal / omental liver metastases Hepatic flexure of colon and duodenum adherent to GB; no frank infiltration

16 MANAGEMENT PLAN? A. Radical Curative Surgery B. Neoadjuvant chemotherapy and reassess for Surgery C. Neoadjuvant chemoradiotherapy and reassess for Surgery D. Palliative treatment options

17 DO WE NEED A BIOPSY? USG guided GB mass ( ) Moderately differentiated adenocarcinoma

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19 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?

20 ON-GOING TRIAL AT TATA MEMORIAL In POLCA-GB trial - CTRT arm (NCT ) 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 , , , and

21 Received 2# Gem - Cis (LD ) CT Abdomen ( ) Residual lesion in GB fossa with liver infiltration- SD Episode of hematemesis on 9th March at home UGI Endoscopy ( ) Acute ulcer in the bulb of duodenum

22 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

23 FURTHER PLAN? A. Continue chemotherapy B. Assess for Surgery

24 Started on ATT (April 2017) After 1 month of ATT posted for Surgery Plan: Radical Cholecystectomy with Distal Gastrectomy

25 Underwent Radical Cholecystectomy with Distal Gastrectomy, D1 resection with ante-colic Gastro-jejunostomy on 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

26 HISTOPATHOLOGY No residual viable tumor Cystic duct margin: free of tumor Gastric and duodenal margin: free of tumor Lymph nodes: 6 negative nodes

27 ADJUVANT TREATMENT 3# Gemcitabin + Cisplatin

28 ABC 02 TRIAL

29 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.

30 FOLLOW UP Asymptomatic at last follow up Normal tumor markers USG A+P: No e/o disease

31 Future Oncology 2015

32 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.

33 TATA MEMORIAL HOSPITAL CRITERIA FOR BR / LA GBC TUMOUR NODE (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 (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)

34 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

35 INVESTIGATIONS Liver Function Tests Bilirubin 0.8 mg% Albumin 4.4 mg% AST/ALT 14 / 15 Hb: 14.6 gm% USG abdomen: Pancreatic mass

36 ROLE OF TUMOR MARKERS IN PANCREATIC CANCER CEA: 7.5 units CA 19-9: 911 units

37 NEXT MODE OF EVALUATION A. Contrast enhanced CT scan (CECT) B. MRI C. PET D. EUS

38 MDCT PANCREATIC PROTOCOL, NCCN (2016)

39 Hypodense mass at pancreatic neck

40 SMV-SV confluence involved Hypodense mass at neck of pancreas Collaterals at SMV-SV junction Distal SMV stump available for reconstruction

41 MDCT ( ) 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

42 ROLE OF STAGING LAPAROSCOPY? A. Yes B. No Indications CA 19-9 > 1000 Pancreatic body mass > 4 cm

43 ROLE OF BIOPSY EUS guided biopsy? USG guided FNAC Adenocarcinoma

44 WITH THIS INFORMATION. Is it, A. Resectable? B. BRPC? C. LAPC?

45 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

46 BRPC: MANAGEMENT PLAN? A. Upfront Surgery B. NACT and reassess for Surgery C. NACT/RT and reassess for Surgery

47 BORDERLINE RESECTABLE: NACT VS NACT/RT, RESULT OF 3 META-ANALYSIS

48 Neoadjuvant Therapy in BRPC: Systematic Review and Meta-Analysis 63% pts resected 87% R0 Median OS 25.9 months (resected) Resection rate FOLFIRINOX (n=64) Gem-based 72% 67% R0 60% 58% G3 /4 Toxicity 53% 30% Tang K. Pancreatology 2016;16: 28-37

49 Toxicity Grade 3 & 4 toxicity 37.3% Tang K. Pancreatology 2016;16: 28-37

50 Plan: NACT and reassess Received 4# FOLFIRINOX

51 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

52 Disease at neck with SMV SV junction involved

53 S. CA units S. CEA 6.75 units PLAN : Pylorus preserving / Classical pancreaticosplenectomy with portal vein confluence resection with SOS PTFE Graft reconstruction ( )

54 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.

55 PANCREATIC HEAD, NECK AND BODY WAS INVOLVED SMV looped

56 RADICAL TOTAL PANCREATECTOMY SPECIMEN

57 ISGPS, TYPE III PORTAL VEIN RESECTION

58 POSTOPERATIVE TUMOR BED

59 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

60 Post op period: Uneventful recovery Received 6# single agent Gemcitabine

61 FOLLOW UP Developed B/L multiple liver metastases recently

62 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

63 Median OS 27 months; in pcr group median OS was not yet met at 60 months; patients without a pcr 26 months In 44% of pcr patients, no recurrence or death was observed. pcr, a negative lymph node status and neodjuvant FOLFIRINOX independent predictors of OS He J, et al. Ann Surg 2018

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