Neoadjuvant Therapy in Pancreatic Cancer

What Is Pancreatic Cancer?

Cancer that occurs in the tissues of the pancreas, an organ that lies in the lower part of the stomach, is pancreatic cancer. The pancreas plays a crucial role in releasing hormones and enzymes that help in digestion and produce hormones that help in the management of blood sugar levels. Several tumor growths occur in the pancreas, cancerous and non-cancerous. The most common type of pancreatic cancer begins in cells that line the duct, which carries digestive enzymes out of the pancreas, known as pancreatic ductal adenocarcinoma. These types are detected seldom at the early stages and the time when it is most curable. They are often asymptomatic until they spread to other organs.

What Are the Causes of Pancreatic Cancer?

The causes of pancreatic cancer are unclear. Some factors have been identified that increase the risk like smoking and certain gene mutations that are inherited. Pancreatic cancer occurs when cells develop changes in their DNA. These mutations tell cells to grow uncontrollably and continue living after normal cells die, these types of cells accumulate and form tumors. If left untreated, these pancreatic cells spread to other body parts.

The risk factors leading to these conditions are:

• Diabetes.

• Pancreatitis (chronic inflammation of the pancreas).

• Smoking.

• Obesity (a complex condition that involves excessive amounts of body fat).

• Old age mostly affects individuals after age 65 years.

• Family history of pancreatic cancer.

• Family history of genetic syndromes like BRCA2 gene mutation, FAMMM syndrome (familial atypical mole malignant melanoma), and Lynch syndrome (hereditary non-polyposis colorectal cancer).

What Are the Signs and Symptoms of Pancreatic Cancer?

The signs and symptoms of pancreatic cancer include:

• Light-colored stools.

• Loss of appetite.

• Unintended weight loss.

• Abdominal pain radiates to the back regions of the abdomen.

• Jaundice (yellowing of mucous membranes of skin, whites of eye).

• Itchy skin.

• Blood clots.

• Fatigue.

• New diabetes diagnosis or worsening uncontrollable present diabetic condition.

What Is the Treatment Provided for Pancreatic Cancer?

Treatment of pancreatic cancer depends on its stage and location and overall health, and personal preferences. The main goal of pancreatic cancer is to eliminate cancer and the treatment includes radiation, surgery, chemotherapy, and a combination of these. In advance cases, the healthcare provider focuses on symptom relief as comfortably as possible.

The surgeries include:

• Surgery for tumors in the pancreatic head.

• Surgery to remove entire pancreas.

• Surgery for tumors in the pancreatic body and tail.

• Surgery for tumors affecting nearby blood vessels.

Along with the above palliative care is given that focuses on providing relief from pain and symptoms of the condition. This is often accompanied with aggressive treatments like chemotherapy, surgery and radiation therapy.

What Is the Role of Neoadjuvant Therapy for Pancreatic Cancer?

Neoadjuvant therapy for resectable pancreatic cancer is an evolving paradigm shift. The adenocarcinoma that is non-metastatic is associated with a high rate of lethality and reoccurrence. Less than half of the affected individuals are able to complete systemic therapy after a successful curative-intent pancreatectomy. Individuals after neoadjuvant therapy have an overall survival rate of 96 %. Adjuvant and neoadjuvant chemotherapy lasts for 3 to 6 months depending on the combination of drugs used and stages of metastatic cancer.

The role of neoadjuvant treatment in pancreatic adenocarcinoma is still a debate in a relative lack of robust data compared with gastrointestinal cancers. Esophageal cancer neoadjuvant chemoradiotherapy is the standard of care for the resectable disease. This treatment is given as a first step to shrink the tumor before the main treatment, which is surgery. The treatment options included in neoadjuvant therapy are radiation therapy, chemotherapy, and hormone therapy.

The newer approach is a procedure called a pancreaticoduodenectomy, this procedure treats tumors of the head and neck and pancreas, then reconnects all structures so the gastrointestinal tract works more effectively.

Using medication like Gemcitabine for treating metastatic pancreatic cancer is most widely used. Other drugs like erlotinib with Gemcitabine, Cisplatin with Gemcitabine, Nab-Paclitaxel with Gemcitabine, and Capecitabine with Gemcitabine combinations are used.

Which Therapies Are Used in Combination with Neoadjuvant Therapy for Pancreatic Cancer?

Pancreatic adenocarcinoma is the third most common cancer that causes death. Surgical resection is the only cure for this condition. But chances of recurrence and survival rates are at a high rate. Neoadjuvant therapy aims to improve long-term cures. The resectable disease is a tumor with no arterial contact and venous tumor contact with the superior mesenteric vein or the portal vein.

• Survival benefits are shown in adjuvant chemoradiation in pancreatic cancer. ESPAC- 1 showed benefits in addition to chemotherapy for individuals with resection using Fluorouracil for 6 months.

• Neoadjuvant therapy has multiple potential benefits including early treatment of the occult condition, micrometastatic disease, and improved compliance with chemotherapy.

• Preliminary results from PREOPANC- 1 have shown good results with resectable and borderline pancreatic cancer. The Gemcitabine-based therapy is given along with neoadjuvant and adjuvant settings.

• Multiagent chemotherapy regimens like 5- FU, Irinotecan (Folfirinox), Oxaliplatin, and Nab-Paclitaxel plus Gemcitabine are used.

• The combination of Gemcitabine and Nab-Paclitaxel had gained more popularity in treating the condition.

• Neoadjuvant Folfirinox has shown decreased nodal positivity, increased OS, and increased margin-negative resection rates.

• Neoadjuvant therapy is performed in cycles and administered in rounds of chemotherapy treatments followed by a resting cycle. These chemotherapy sessions are given via I.V or orally. The number of cycles varies from patient to patient

What Are the Main Advantages of Neoadjuvant Therapy in Pancreatic Cancer?

The main advantages of neoadjuvant chemotherapy are :

• Overall survival and reduced recurrence rate, same as post-chemotherapy.

• Serves as in vivo and sensitivity test.

• Increases rate of breast-conserving therapy.

• Facilitates cancer biology study.

Conclusion

Neoadjuvant therapy plays an important role in multimodal treatment in individuals with borderline resectable pancreatic cancer. It has a key role in individuals with locally advanced tumors and allows surgical resection in relevant proportions. Still, evaluation of many trials continues to determine the potential benefit of neoadjuvant therapy in pancreatic cancer along with chemotherapy and radiation approaches. Advances in this field will surely lead to more sophisticated techniques in treating, assessing, and individualizing methods to guide better treatment.