RECENT ADVANCES IN PANCREATIC CANCER

Dr.E.Kaushik Kumar Department of General Surgery

Stanley Medical College Hospital,Chennai

• Molecular Genetics and Tumour Biology• Early Detection of Precursor Lesions• Investigation Modalities• Surgical Management• Adjuvant modalities

Molecular Genetics and Tumour Biology• Two eras

• Early Detection of Precursor Lesions– PanIN– IPMN– Mucinous Cystic Neoplasm

Investigation Modalities

• TAUS• EUS• IOUS• MD-CT• MRCP• Nuclear Imaging• Tumour Markers

ULTRASOUND

• Screening• 95.8% sensitive >3cm lesions• Newer machines- Tissue Harmonic Imaging• Colour Doppler • IV Contrast imaging-100% specific for vascular

involvement• PPV for unresectabilty-94%

EUS• <3cm tumours,ampullary lesions• Staging and resectability• Reassessment after NAC• EUS-FNA- 95% sensitivity,97% specificity,PPV

92%, 100% NPV• Therapeutic options

– Intra-tumoral therapy(activated lymphocytic cultures,viral vectors,oncolytic viruses)

– RFA/Cryotherapy– Celiac plexus neurolysis

Homogenous echoes

Hypoechoic,irregular borders

Cyst- anecohic

Endocrine tumours-iso-echoic

Improper vascular involvement, invasive,costly,operator dependent

Intra-operative US

• Depth of invasion

• Maximal longitudinal extent

• Vascular invasion

• Degree of resectability(20-35% will be unresectable)

• Liver mets

• Localise islet cell tumours

MDCT• Ill-defined, hypoattenuating focal mass with dilatation of

the upstream pancreatic and or biliary duct• Arterial,Pancreatic and portal phases• Very high spatial and temporal resolution• Pancreatic Protocol-1 to 3 mm slice collimation• challenging in the setting of

– pancreatitis forming mass effects– in the presence of loco-regional lymph node

involvement – small hepatic metastasis

• Vascular involvement include– Tumor involvement for one half of the vessel′s

circumference– Focal narrowing of the vessels – Dilatation of peripancreatic veins.

• Perfusion imaging– Angiogenesis in tumours– Predict response to CCRT

MRI-MRCP

• High soft tissue contrast resolution– Assessment of peripancreatic fat infiltration– Evaluation of vascular encasement– Peritoneal deposits and lymph nodal involvement

• MRS-differentiate CFP from pancreatic cancer– proton MRS, CP shows less lipid than pancreatic

carcinoma due to difference in fibrous tissue content in the two conditions

• Diffusion-weighted MRI differentiates the subtypes of pancreatic endocrine neoplasms – Tumor cellularity – Extracellular fibrosis – Various apparent diffusion coefficient (ADC)

values in these tumors

MRI vs MDCT

Sensitivity Specificity

Anderson et al 92% v 76% 85% v 69%

Hanninen et al 97% 81%

Park et el (GE-MRI) 83-85% v 83% 63% v 63-75%

Grenacher et el 82-94% v 100%

Bigat et al 84% v 91%

Nuclear Imaging

• Newly developed PET scanners can detect small PCs up to 7 mm in diameter

• Unsuspected Bone metastasis(40%)

• Inflammatory pathology

• Tumour viability

• Response to treatment

Optical coherence tomography

• Infrared light to produce high-resolution, cross-sectional, subsurface imaging of the microstructure.

• Recognize different patterns of

the duct wall structure in

neoplastic and non-neoplastic

conditions• High diagnostic accuracy,

better than brush cytology

Tumour MarkersMarker Sensitivity Specificity

CEA 45% 75%

CA 19-9 80% 43%

CA 242 60% 76%

CEA + CA 19-9 37% 84%

CEA + CA 242 34% 92%

• CA494• CEACAM1• PTHrP• TuM2-PK• CAM 17.1• Serum beta HCG

Surgical Management

• Resectability criteria– Resectable– Borderline Resectable– Unresectable

• Laparoscopy– Staging– Therapeutic– Safe and Better outcome

• Robotic Surgery– 3-Dimensional– Dexterity– Ergonomics

Adjuvant modalities

• FOLFIRINOX(5-fluorouracil, leucovorin, irinotecan, oxaliplatin)

– ACCORD trial -median overall (11.1 mo vs 6.8 mo)– Grade 3-4 toxicities

• Gemcitabine + nab-Paclitaxel (MPACT)– Improved median overall survival (8.5mo vs 6.7 mo) – Improved 1-year survival (35% vs 22%)– Improved 2-year survival (9% vs 4%)– Improved objective response rate

• Gemcitabine plus erlotinib– improved progression-free survival and

overall survival

– hNET1 expression Gemcitabine response

S-1

• An oral 5-fluorouracil (5-FU) prodrug– Tegafur (a prodrug of 5-FU)– Gimeracil [a potent dihydropyrimidine dehydrogenase

(DPD) inhibitor]– Oteracil(an inhibitor of phosphorylation of 5-FU in GIT)

• First-line Chemotherapy for Metastatic/Locally Advanced Pancreatic Cancer

• Second-line Therapy After Gemcitabine Failure• CRT For Locally Advanced Pancreatic Cancer• Adjuvant Chemotherapy For Resected Pancreatic Cancer• Improved ORR

• Neo-Adjuvant ChemoRadiotherapy– Chemotherapy provides control for a micro-

disseminated disease & also acts as a radiation sensitizer

– Radiotherapy(RT) may have a huge impact on the local control of the disease.

• Upfront chemotherapy followed by CRT– Early therapeutic approach may use not only

RT-sensitizing drugs and drugs that are more

effective against cancer such as 5-FU and Gemcitabine or Capecitabine

– Select patient who did not progress, thus avoiding the additional toxicity of unnecessary Radiotherapy (RT)

• End point – Resectability as per NCCN

• IORT– When followed after pre-operative

chemotherapy and surgery gives a 5-yr local control of 23.3%

Multidisciplinary

• Mortality and morbidity directly proportional to Institutional Volume of cases

• “A persistent nihilism of clinicians towards PC and pancreatectomy may be the most significant correctable factor that contributes to the current poor long-term outcomes of PC.”

• Birkmeyer et al,Bilimoria et al

• What have we understood?

• What has improved?

• Where do we stand?

• What needs to be done?

References• Blumgart textbook of HPB Diseases,5th edition• World Journal of Gastroenterology(2001-2014)

– Pancreatic cancer: Advances in treatment

– Recent advances in the surgical treatment of pancreatic cancer

– Selection criteria in resectable pancreatic cancer: A biological and morphological approach

– Imaging diagnosis of pancreatic cancer: A state-of-the-art review

– Diagnostic Imaging for Pancreatic Cancer Computed Tomography, Magnetic Resonance Imaging, and Positron Emission Tomography

– Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010

– S-1 in the treatment of pancreatic cancer Kentaro Sudo, Kazuyoshi Nakamura, Taketo Yamaguchi

– Recent standardization of treatment strategy for pancreatic neuroendocrine tumors Masayuki Imamura

– Neoadjuvant strategies for pancreatic cancer

Thank You