Pathological complete response in pancreatic adenocarcinoma with FOLFIRINOX

Abstract

The report describes a patient who presented to our centre with abdominal pain and significant weight loss due to adenocarcinoma of the tail of the pancreas. The cancer was deemed as ‘resectable disease associated with morbid surgical outcomes’ due to the local involvement of the vessels and adjacent organs. Given the patient’s excellent performance status, the patient underwent neoadjuvant chemotherapy with folinic acid, fluorouracil, irinotecan and oxaliplatin to downstage the tumour for less morbid surgical resection. The patient underwent 12 cycles of chemotherapy with serial imaging which demonstrated positive response to treatment and surgical resection was performed. Surgical pathology revealed no residual tumour and imaging was negative for any extrapancreatic tumour metastasis. This is an unusual case as pancreatic malignancy is usually lethal with poor survival outcomes.

Background

Pancreatic cancer accounts for 3.2% of all new cancer diagnosis in the USA with an estimated 53 670 cases reported in 2017.¹ This cancer carries a poor prognosis given its insidious onset and progression. The overall 5-year survival rate in victims of such cancer is reportedly around 8.2% with approximately 50% of the patients diagnosed as metastatic disease on initial presentation. Only 15%–20% of pancreatic cancers are potentially resectable at the time of diagnosis.²

The current guidelines of American Society of Clinical Oncology suggest primary surgical resection in patients with: (1) No evident metastases, (2) Higher Eastern Cooperative Oncology Group (ECOG) status appropriate for major abdominal surgery, (3) CA 19–9 level in acceptable range suggestive of localised disease and (4) No localised invasion of the primary tumour and mesenteric vasculature as evident on imaging.³ Neoadjuvant therapy is not required for patients with surgically resectable disease, however, it is recommended for patients with borderline resectable disease for downstaging to increase success during surgery and render negative margins. The current National Comprehensive Cancer Network (NCCN) guidelines are being updated to consider neoadjuvant chemotherapy in patients with resectable disease as it helps determine the biology of cancer before the surgery. If the tumour progresses on chemotherapy, then surgery is appropriately abandoned. If the tumour responds, then chemotherapy is continued even after surgery.^{4 5} Previous studies have shown that 50% of the patients are able to undergo resection after receiving neoadjuvant therapy.⁶ The other advantage of neoadjuvant chemotherapy is to treat micrometastatic disease.^{7 8} Although not clearly established, folinic acid, fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine plus nanoparticle albumin bound paclitaxel have been supported by recent guidelines.^{9 10}

This case highlights a patient with resectable adenocarcinoma of tail of pancreas with morbid surgical outcome if attempted at resection upfront, who achieved pathological complete response (pCR) with neoadjuvant FOLFIRINOX regimen and downstaged the tumour to enable surgical resection with less morbidity.

Case presentation

A 58-year-old Caucasian man presented to his primary care physician complaining of chronic left upper quadrant abdominal pain and significant weight loss of 23 pounds in 6 months. He endorsed smoking in the remote past and only consumed alcohol socially. Family history was significant for ovarian cancer in mother, breast cancer in maternal aunt and maternal half-sister, and oesophageal cancer in his maternal aunt.

Investigations

An initial ultrasound (US) of abdomen revealed a large hypodense, non-enhancing collection measuring about 9 cm in the tail of the pancreas. A follow-up CT scan of abdomen showed a 9.2×6.7×7.6 cm lesion in the central body and tail of the pancreas with prominent peripancreatic lymph nodes. No pancreatic ductal dilation was evident on scan (figure 1). A chest CT scan revealed no thoracic metastatic disease. Endoscopic US revealed a 41×49 mm hypoechoic lesion with areas of cystic degeneration in the body and tail of the pancreas without coeliac axis involvement. The width of the pancreatic duct and common bile duct was respectively measured as 1.8 mm and 3.7 mm. Fine-needle aspiration cytology demonstrated adenocarcinoma of the pancreas.

Figure 1.

CT abdomen obtained before treatment demonstrating pancreatic tail mass measuring at 9.2×6.7×7.6 cm encasing the splenic artery and occluding the splenic vein 151×120 mm.

Treatment

The patient was evaluated to be ECOG grade 0 given his active physical life with no restriction from his underlying cancer otherwise noted. His radiological staging at the time of diagnosis was T3NXM0 due to gastric wall involvement and splenic blood vessel encasement. Total gastrectomy, pancreatectomy and splenectomy would be a very morbid surgery. The patient was given the option of: (1) Undergoing surgery before chemotherapy and (2) Undergoing neoadjuvant chemotherapy to try and downstage the tumour and then pursue surgery. Given the patient’s preference, he was started on FOLFIRINOX regimen (irinotecan 180 mg/ m²; 5-fluorouracil 400 mg/m², oxaliplatin 85 mg/m² and folinic acid 400 mg/m²) for a total of 12 cycles with imaging performed at regular intervals. His CA 19–9 count was 1297 U/mL prior to initiation of therapy.

A reduction in tumour size (3.4×2.6 cm) was evidently displayed on a repeat CT scan obtained after the 12th cycle without any metastatic disease (figure 2). Also, a declining trend in CA 19–9 was observed throughout the course of illness (figure 3). The patient underwent distal pancreatectomy, splenectomy and partial gastrectomy following chemotherapy. No local tumour invasion was observed during the surgery. The hospital course was complicated with postoperative atelectasis and pneumonia, however, the patient responded to antibiotics and was discharged to home in stable condition. Surgical pathology of the specimen showed no residual tumour in the pancreas and in the resected lymph node (pCR) (ypT0). The patient received adjuvant chemotherapy with gemcitabine and capecitabine for 9 months after surgery.

Figure 2.

Preoperative CT scan after 12 cycles of FOLFIRINOX. Notice the decrease in size of the tumour compared with figure 1.202×172 mm. FOLFIRINOX, folinic acid, fluorouracil, irinotecan and oxaliplatin.

Figure 3.

Trend of the patient’s CA 19–9 levels throughout the course of disease. Notice the decreasing levels immediately after cycle one with normal level prior to surgery. 192×82 mm (300×300 DPI).

Outcome and follow-up

CA 19–9 normalised following surgery. CT scans after 3 months and 9 months after surgery and CA 19–9 level is within normal limits and does not reveal any evidence of recurrent cancer. The patient remains cancer free at 9 months after surgery and continues on surveillance.

Discussion

We describe here a case of a successfully treated resectable adenocarcinoma of pancreas with neoadjuvant chemotherapy with FOLFIRINOX regimen followed by surgical resection. The case highlights the importance of imaging and radiological staging of the disease prior to initiating treatment to achieve the best possible outcome for the patient.

The NCCN guideline divides the disease into three distinct categories based on radiological findings: resectable, borderline resectable and unresectable/metastatic disease.¹¹ This classification is important as it assists in selecting the treatment modality and also predicts the outcome following treatment. Borderline resectable disease is described as:

1. For tumours of the head and uncinate process, at least one of the following criteria should be fulfilled: (1) the tumour encases the Superior Mesenteric Vein with contour irregularity or vein thrombosis of the vein, but is with suitable vessel proximal and distal to the site of involvement (2) any tumour contact with the inferior vena cava (3) tumour contact with common hepatic artery without extension to the celiac axis or hepatic artery bifurcation (4) abutment of the superior mesenteric artery (5) tumour contact with variable anatomy (accessory arteries) that may affect surgical planning.

2. For tumour of the body and tail of tail of pancreas, at least one of the following should be present: (1) abutment of the coeliac axis (2) encasement of the coeliac axis without the involvement of the aorta and with an intact and uninvolved gastroduodenal artery.¹¹

In our case, pancreatic cancer showed gastric wall involvement and splenic blood vessel encasement. Although, the patient was classified as having ‘resectable disease’, however, total gastrectomy, pancreatectomy and splenectomy would be a very morbid surgery.

Currently, no definite neoadjuvant chemotherapy regimen has been proposed for managing these resectable pancreatic cancers. Recently, Katz et al concluded a trial and showed that 68% of patients with borderline pancreatic cancer who underwent therapy with modified FOLFIRINOX regimen followed by capecitabine-based chemoradiation underwent successful surgical resection. The median survival for these patients were 21.7 months (95% CI 15.7 to not reached).¹² Similarly, Rombouts et al reported pCR in 7% of resected specimen after the patients were initially diagnosed with locally advanced pancreatic cancer and underwent therapy with either FOLFIRINOX alone, modified FOLFIRINOX or in combination with radiation therapy.¹³

We reviewed the literature and found a handful of case reports that exhibited complete pathological response after FOLFIRINOX therapy alone. Palmarocchi et al reported a case of borderline resectable pancreatic cancer of the head treated with full dose of FOLFIRINOX for six cycles. The patient underwent duodenopancreatectomy and displayed pCR on final pathology. The patient refused adjuvant therapy and unfortunately had recurrence after 4 months from the surgery.¹⁴ A similar case was reported by Pozza et al of a patient who achieved pCR following pancreatectomy after five cycles of FOLFIRINOX, but later developed multiple brain metastasis.¹⁵ Two cases reported by Gostimir et al and Valeri et al, respectively, remained disease free after 14 months who were initially diagnosed with pancreatic cancer of the head. One of the patients received 13 cycles of chemotherapy and underwent pancreatectomy while the other received eight cycles of chemotherapy and underwent pancreaticoduodenectomy.^{16 17} Our patient received a total of 12 cycles of chemotherapy with FOLFIRINOX and underwent pancreatectomy, splenectomy and partial gastrectomy and remains disease free to date (12 months).

In conclusion, it is extremely paramount to radiologically and surgically categorise pancreatic cancer to guide the most optimum therapy to increase survival outcomes. This case highlights the importance of early induction chemotherapy with FOLFIRINOX regimen followed by surgical resection for pancreatic cancer to achieve the best possible outcome for the patient by downstaging and facilitating a less morbid surgery. Additionally, in this case FOLFIRINOX contributed to long-term disease-free outcome and possibly even cure.

Patient’s perspective.

When I was first diagnosed I felt devastated, more so for my family. When every doctor that I came in contact with asked me how I knew there was a problem it made me realise just how advanced and serious my condition actually was. The final blow was when I was turned down for the clinical trial because they didn’t feel that it would be an accurate or fair representation of their trial because of my advanced condition. I felt at this point my choices were to do nothing and live out what time I had left or take the most aggressive treatment available and possibly extend the amount of time I had to spend with my family. After choosing the course of treatment my family and I also researched other options that might help with my condition and treatment. I changed my diet by taking out all processed food and eliminating tap water. I started taking hemp oil twice daily, and other supplements that had positive feedback for the treatment of cancer and the side effects of chemotherapy treatments.

Learning points.

• Pancreatic cancer needs to be radiologically and surgically categorised to guide the most optimum therapy to increase survival outcomes.

• Consideration should be given to neoadjuvant chemotherapy even for surgically resectable disease to downstage tumour and convert a more morbid surgery to a less morbid surgery.

• Though rare, achieving pathological complete response with aggressive chemotherapy is possible in pancreatic cancer. This may serve as a biomarker for long-term disease-free and overall survival.