Pancreatic Cancer

Background

Clinical KeyMore than 45,000 new cases of pancreatic cancer are expected to be diagnosed each year, and the rate has increased over the past decade. Pancreatic cancer is difficult to detect at early stages, in part because the pancreas is a deep organ, physicians do not feel early tumors, and blood tests are not available for early detection.

Thus, more than 80% of the time pancreatic cancer is diagnosed, it has already spread to be unresectable. It has the third-highest fatality rate of all cancers, and the 5 year survival rate is only 8%.

What causes pancreatic cancer is not known. However, the risk for pancreatic cancer is higher among older individuals, African Americans, and men. Smoking, obesity, and diabetes also appear to increase the risk for pancreatic cancer. Chronic pancreatitis, cirrhosis of the liver, diet, and occupational exposures have also been cited as potential risk factors.

Current Treatment

Therapeutic options for pancreatic cancer include surgery, radiation, chemotherapy, ablative techniques, and embolization. The precise treatment regimen depends on location and stage of the cancer. By American Cancer Society estimates, survival rates following conventional therapies are 12% to 14% for earlier-stage cancers and 1% to 5% for later stages.

Surgery
Surgery is the only potentially curative treatment for pancreatic cancer. However, it is one of the most difficult operations, both for the surgeon and the patient, so it is performed primarily when imaging suggests that the entire tumor can be removed. One type of surgery is the Whipple procedure, which removes the head and sometimes the body of the pancreas, along with the gall bladder, nearby lymph nodes, and parts of the small intestine, common bile duct, and stomach. Another type of surgery is distal pancreatectomy, which removes only the tail and part of the body of the pancreas.

In many cases, surgeons begin the operation with the intent to cure but discover that it is not possible. In those cases, the surgeon may continue the procedure to relieve symptoms and prevent complications such as blockages in the bile duct or intestinal tract.

Patients treated with surgery tend to survive longer than those who are not. However, only one in six patients with pancreatic cancer receive surgery.

Radiation
Radiation therapy involves focusing an external beam of high-energy X-rays or particles to kill cancer cells. Radiation therapy does contains risks for secondary malignancies and for those with poor wound healing. It is also still under evaluation in clinical trials for pancreatic cancer.

Chemotherapy
Chemotherapeutic drugs, which kill cancer cells, are given by mouth or by injection. For resectable cancers, chemotherapy may delay recurrence for as long as six months. For advanced pancreatic cancer, chemotherapy with gemcitabine has been the standard treatment. In general, chemotherapy does not work well for pancreatic cancer.

Ablative Techniques
Ablative techniques can be used for local tissue destruction. With these techniques, a probe or needle can be inserted into the tumor to thermally destroy tissue around the needle tip and reduce tumor symptoms. Radiofrequency waves or microwaves are passed through the probe to heat and destroy the tissue. Alternatively, liquid nitrogen or liquid carbon dioxide can be passed through the probe to freeze and destroy it.

Embolization
Embolization kills the tumor by blocking its blood supply. A catheter is inserted, usually through an artery in the groin area, and threaded into the artery feeding the tumor. Plain or radioactive beads are injected to block the artery. Sometimes, chemotherapy is injected before the beads.

Focused Ultrasound Treatment

Focused ultrasound has the potential to offer a non-invasive ablative technique for palliation in patients with pancreatic cancer. Guided by ultrasound or magnetic resonance imaging, the physician directs a focused beam of acoustic energy toward the cancer. This beam heats and destroys the cancerous tissue without damaging nearby tissues or structures.

As a potentially non-invasive technique that does not rely on ionizing radiation, focused ultrasound may offer benefits including:

  • shorter recovery time
  • more precise targeting of tumor and metastases, resulting in lower risk for complications
  • the procedure can be done repeatedly

However, not all patients will be suitable for focused ultrasound treatment, as in some cases where the bowel blocks pathway of the beam. There is also potential for damage to non-targeted tissue, such as the skin.

Pre-clinical Research

Pre-clinical research with focused ultrasound can enable a better understanding of pathologic process and yield improved treatments of the underlying disease by delivering therapeutic agents, enhancing agent affinity, or augmenting the immune response.

Studies include work at University of Utah looking at the best method of drug delivery, including mechanical, thermal and ultrasound activated perfluorocarbon nanoemulsions as options.

Work at the University of Washington found that in mice with pancreatic cancer, an increased amount of doxorubicin uptake occurred in the setting of focused ultrasound generated hyperthermia compared to controls.

The Institute of Cancer Research in London is comparing several aspects of immunotherapy in pre-clinical studies of pancreatic cancer. They are comparing the tumor volume, survival, and levels of cytotoxic T cells from mice treated with focused ultrasound, focused ultrasound plus immune checkpoint inhibitors, or focused ultrasound degradation of the tumor microenvironment in an effort to identify the optimal approach.

Clinical Trials

There has been anecdotal evidence that use of focused ultrasound inside the main tumor has resulted in stimulation of the immune system, resulting in significant reduction in lymph nodes outside of the treatment region. This benefit has been seen frequently enough to ensure that it is a valid observation, yet efforts to demonstrate it consistently have been elusive. There is considerable work aimed at taking this beneficial effect and making it a more reliable part of the treatment plan.

Additional focused ultrasound impacts may produce results in patients with pancreatic cancer. The mechanical effect of hyperthermia may help with chemotherapy binding, and sonodynamic therapy may also assist in the local impact of chemotherapeutic agents. Focused ultrasound can also be very helpful in reduction in the pain from pancreatic cancer, either as part of an overall plan for tumor control or as tool used exclusively for pain control. These approaches are encouraging, but still very early in adoption, so ongoing work continues to identify the optimal use of these techniques.

A clinical trial at the University of Roma La Sapienza in Italy has expanded access to treatment in a study exploring the feasibility and clinical performance of focused ultrasound in pain palliation and tumor control. More information about this trial can be found at http://clinicaltrials.gov/show/NCT01786850.

University of Roma La Sapienza
Rome, Italy
Department of Radiological Sciences
MRgFUS & Cardiovascular Imaging Unit
Alessandro Napoli, MD, PhD

+390649974540

The Focused Ultrasound Foundation is working with leading sites to implement a registry to capture data from pancreatic cancer patients to help guide future decisions about optimal clinical care, safety and regulatory factors, and reimbursement concerns. The goal of this registry is to capture early data to expedite the availability of focused ultrasound improvements for patient care as soon as possible.

Regulatory Approval and Reimbursement

The Model JC system manufactured by Chongqing Haifu has been approved in Europe for palliative treatment in patients with pancreatic cancer.

Focused ultrasound treatment for patients with pancreatic cancer is not universally reimbursed by medical insurers.

 

Notable Papers

Yu MH, Lee JY, Kim HR, Kim BR, Park EJ, Kim HS, Han JK, Choi BI. Therapeutic Effects of Microbubbles Added to Combined High-Intensity Focused Ultrasoundand Chemotherapy in a Pancreatic Cancer Xenograft Model. Korean J Radiol. 2016 Sep-Oct;17(5):779-88. doi: 10.3348/kjr.2016.17.5.779.

Payen T, Palermo CF, Sastra SA, Chen H, Han Y, Olive KP, Konofagou EE. Elasticity mapping of murine abdominal organs in vivo using harmonic motion imaging (HMI). Phys Med Biol. 2016 Aug 7;61(15):5741-54. doi: 10.1088/0031-9155/61/15/5741.

Diana M, Schiraldi L, Liu YY, Memeo R, Mutter D, Pessaux P, Marescaux J. High intensity focused ultrasound (HIFU) applied to hepato-bilio-pancreatic and the digestive system-current state of the art and future perspectives. Hepatobiliary Surg Nutr. 2016 Aug;5(4):329-44. doi: 10.21037/hbsn.2015.11.03.

Marinova M, Strunk HM, Rauch M, Henseler J, Clarens T, Brüx L, Dolscheid-Pommerich R, Conrad R, Cuhls H, Radbruch L, Schild HH, Mücke M. [High-intensity focused ultrasound (HIFU) for tumor pain relief in inoperable pancreatic cancer : Evaluation with the pain sensation scale (SES)]. Schmerz. 2016 Jul 11. German.

Strunk HM, Henseler J, Rauch M, Mücke M, Kukuk G, Cuhls H, Radbruch L, Zhang L, Schild HH, Marinova M. Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer. Rofo. 2016 Jul;188(7):662-70. doi: 10.1055/s-0042-105517.

Ning ZY, Cheng CS, Xie J, Chen QW, Xu LT, Zhuang LP, Zhang CY, Song LB, Shi WD, Zhu XY, Wang P, Wang K, Meng ZQ. A retrospective analysis of survival factors of high intensity focused ultrasound (HIFU) treatment for unresectable pancreatic cancer. Discov Med. 2016 Jun;21(118):435-45.

Petrou A, Moris D, Paul Tabet P, David Wensley Richards B, Kourounis G. Ablation of the locally advanced pancreatic cancer: An introduction and brief summary of techniques. J BUON. 2016 May-Jun;21(3):650-8.

Lv W1, Yan T1, Wang G1, Zhao W1, Zhang T1, Zhou D1. High-intensity focused ultrasound therapy in combination with gemcitabine for unresectable pancreatic carcinoma. Ther Clin Risk Manag. 2016 May 2;12:687-91. doi: 10.2147/TCRM.S90567.

Linecker M, Pfammatter T, Kambakamba P, DeOliveira ML. Ablation Strategies for Locally Advanced Pancreatic Cancer. Dig Surg. 2016;33(4):351-9. doi: 10.1159/000445021.

Click here for additional references from PubMed. 

     

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