What's On News September 2017 Pancreatic Cancer Case Study

News

Pancreatic Cancer Case Study

Thursday 9 February 2017

This case study has been written by Dr Andrew Barbour who is a general surgeon specialising in upper gastrointestinal, pancreatic, melanoma and sarcoma surgery.

Mr W initially presented with mild abdominal discomfort. He was investigated with a CT of the abdomen that showed a 3.5 cm hypodense lesion in the body/neck of the pancreas. The scan showed it was localised with no invasion of the splenic artery but the plane with the splenic vein was not clear. Most importantly, there was no evidence of metastatic disease.

Mr W then underwent an endoscopic ultrasound which permitted a needle biopsy to be performed to obtain a tissue diagnosis. This confirmed the lesion to be a pancreatic ductal adenocarcinoma (PDAC). EUS-guided FNA of the pancreas is able to confirm the diagnosis more than 90 per cent of the time and is recommended before the final treatment plan is formulated.

Due to the aggressive nature of pancreas cancer, Mr W underwent a laparoscopy to complete his staging. At the laparoscopy he was found to have a nodule that had developed at his umbilicus in the two weeks after his initial presentation. The laparoscopy showed no other evidence of peritoneal metastatic disease. The umbilical nodule was excised and pathology showed metastatic pancreatic ductal adenocarcinoma in the nodule. This was in keeping with the serum CA 19.9 of 3000.

As a result of the investigations Mr W was diagnosed with stage four pancreas cancer and it was determined that the best course of action would be for him to receive palliative chemotherapy.  In the context of stage four pancreatic cancer, it was felt a resection of the primary disease would not be beneficial.  

Mr W was treated with Gemcitabine and Nab-Paclitaxel (Abraxane). This is a newer, well tolerated regimen with superior outcomes for PDAC compared with gemcitabine alone, the previous standard of care for PDAC.

He was treated with chemotherapy for nine months and had an excellent response in his serum CA 19.9. Essentially, his CA 19.9 normalised to 20 (upper limit of normal being <37). However towards the end of his treatment his CA 19.9 rose to 320. Mr W’s CT PET scan at that time, after nine months of treatment, showed no evidence of metastatic disease. The primary lesion was now a little larger at 3 cm in size with a 1.7 cm area of FDG uptake in the centre of it. It was still technically resectable.

This was a very unusual situation: no evidence of systemic progression but the primary disease remaining in situ. After discussion among the multidisciplinary team and careful consultation with Mr W, it was collectively decided to go forward with radical resection of the primary tumour which involved subtotal distal pancreatectomy and splenectomy en-bloc. Histopathology showed viable adenocarcinoma with clear margins.

Mr W is now four years disease free since his surgery. He has not had further chemotherapy and his CA 19.9 remains within normal limits.

Mr W’s case is very instructive for a number of reasons. Pancreas cancer is one of the most lethal tumour types with a five year survival typically of just five per cent. Each year over 2500 Australians are diagnosed with pancreas cancer, making it a significant health problem and there is clearly a pressing need to find alternative approaches to treatment. Only 20 per cent of patients are able to undergo surgical removal of their primary tumour (in the absence of metastatic disease) and among these patients the five year survival rate is still only 20 per cent.

In recent years, Mater has contributed to the application of next generation sequencing through the Australian Pancreatic Genome Initiative (APGI) which has revealed the complex genomec landscape for pancreatic cancer. The NHMRC funded project has uncovered the mutational processes that occur during the development and progression of pancreatic cancer and identified some new or repurposed existing therapeutic opportunities for pancreatic cancer patients.

Due to the large degree of genomic heterogeneity identified in pancreatic cancer, a personalised approach to treatment seems particularly warranted. The work of the APGI has identified frequently mutated genes in KRAS signalling, cell cycle and the TGF beta/Notch signalling pathways. It has also shown abnormalities within chromatin modification and in particular DNA repair pathways of particular interest. These include abnormalities in genes such as BRCA1 and BRCA2 which are known to predispose to breast cancer. Abnormalities in the DNA repair pathway have made this sub group of pancreatic cancers highly susceptible to chemotherapies involving Platinum-based agents in particular. Indeed it has been shown that patients with impaired DNA repair pathways have shown extremely good responses and improved survival with chemotherapy.

This data suggests patients like Mr W, who can be considered an extreme responder, are likely to have defects in their DNA repair pathway. Further research is needed to provide markers that we can use in the clinic and this is an area of active research. 

This case study also illustrates the benefit of chemotherapy for pancreatic cancer, in particular its role prior to surgery. The vast majority of patients are usually able to tolerate chemotherapy before surgery while only 50 to 60 per cent might be able to tolerate chemotherapy afterwards. Chemotherapy also can identify patients whose tumours are extremely aggressive where surgery may not provide an improvement in survival. This concept of preoperative treatment has been explored in the recently completed GAP trial (sponsored by the Australasian Gastrointestinal Trials group and led by myself as the principal investigator) that explored the use of pre and post-operative chemotherapy. This approach was safe and feasible. Further study will be required to determine whether this provides better outcomes compared with the standard approach of post-operative chemotherapy.

There has been much progress in pancreatic cancer within the past few years. Mr W’s case illustrates that good outcomes are possible with newer chemotherapeutic agents. As we further unlock the molecular biology that underpins pancreatic cancer development and progression, we will see further progress. We can seek to apply more precise treatments: the right treatment to the right patient, at the right time.