Research conducted in the Kanzius/Curley Lab at The University of Texas M.D. Anderson Cancer Center for the first time demonstrates that radiofrequency fields can treat pancreatic andenocarcinomas[1]. The researchers found that noninvasive radiofrequency (RF) fields were effective in controlling relatively large pancreatic cancer cells without any injury to surrounding tissue or changes in subject behavior.
Despite many decades of research pancreatic carcinomas remain one of the deadliest cancers with few effective treatments. In the United States an estimated about 43,000 individuals will be diagnosed annually with this condition, and 37,000 will die from the disease. [2,3] The prognosis is poor, the disease rarely curable and the overall survival (OS) rate of less than 4%. Complete remission is still rare. [3,4,5,6]
According to the National Cancer Institute, the highest cure rate occurs in patients with a tumor which is truly localized to the pancreas. However, this stage of the disease accounts for fewer than 20% of all cases. In patients with localized disease and small cancers (<2 cm) with no lymph node metastases and no extension beyond the capsule of the pancreas, complete surgical resection can yield actuarial 5-year survival rates of 18% to 24%.[7]
Increased incidence
During the past several decades a pancreatic carcinoma has had a markedly increased incidence. The disease has become the fourth leading cause of cancer death in the United States. Despite the high mortality rate associated with pancreatic cancer, its etiology is poorly understood. [7]
Pancreatic cancer is not a single disease. In fact, there are as many as twenty different tumors lumped together under the general term ?cancer of the pancreas.? The majority of pancreatic carcinomas, about 95%, are exocrine adenocarcinomas, because they begin in the exocrine cells that produce enzymes to aid in digestion. Adenocarcinomas usually originate in the glandular cells lining the pancreatic duct and generally occur in the head of the pancreas which is nearest the first segment of the duodenum or small intestine [5]
The remaining 5% include adenosquamous carcinomas, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with osteoclast-like giant cells. [8]
Pancreatic endocrine tumors, also called neuroendocrine or islet cell tumors, arise from the types of pancreatic cells that produce hormones such as insulin, glucagon and somatostatin. Endocrine tumors, categorized as functional (producing hormones) or nonfunctional (not producing hormones), may be benign or malignant and tend to be slower growing than exocrine tumors. While the majority of functional endocrine tumors are benign, more than 90% of nonfunctional endocrine tumors are malignant.[8]
DiagnosisBecause in the earlier stages pancreatic carcinoma is often asymptomatic, and the later symptoms are usually nonspecific and varied [9] the disease is often not diagnosed until it is advanced. Physical examination and blood test results are often normal.[5] Commonly used tests used in diagnosing pancreatic cancer include ultrasound scans, endoscopic retrograde cholangiopancreatography. However, the most accurate diagnostic test is computed tomography (CT).[5]
Treatment
Depending on the type and stage of the cancer, treatment options include surgical resection, radiation therapy and chemotherapy. Surgical resection, which is performed on the 10 to 20% of people in whom it is believed that the cancer has not spread, involves the removal of the pancreas alone or the pancreas and the duodenum together. In most instances surgical resection is followed by adjuvant chemotherapy and radiation therapy. Since resection may lead to long-term survival and provides effective palliation, surgical resection remains, when feasible, the primary treatment option.[10, 11,12]. On the other hand, because data from randomized clinical trials is statistically underpowered and provide conflicting results, the role of postoperative therapy remains controversial.
Targeted therapy against antigens overexpressed in pancreatic cancer, such as epidermal growth factor receptor (EGFR-1), has only been minimally successful despite its use in other antigen overexpressing cancers [13]
Clinical Trials: Valid Treatment Options
Because, in general, the survival rate of patients with any stage of pancreatic exocrine adenocarcinomas is poor, clinical trials are appropriate alternatives for treatment of these patients and should be considered prior to selecting palliative approaches.[14]
Ongoing research
In the study in the Kanzius/Curley Lab at The University of Texas M.D. Anderson Cancer Center subjects were exposed to 10 minutes of nonionizing radiofrequency (RF) radiation followed by 36 hours of treatment using targeted gold nanoparticles (AuNP).
Gold nanoparticles (AuNP) are potentially therapeutic because of the safety demonstrated thus far and their physiochemical characteristics. The researchers used the astounding heating rates of AuNPs in nonionizing radiofrequency (RF) radiation to investigate human pancreatic xenograft destruction in a murine model. The design showed that the Kanzius RF machine alongside these particular nanoparticles create an effective formula for controlling pancreatic cancer cells.
Commenting on the trial results, Steven Curley, Chief of Gastrointestinal Tumor Surgery and Program Director of Multidisciplinary Gastrointestinal Cancer Care at The University of Texas M. D. Anderson Cancer Center said: ?These experiments demonstrate that the Kanzius RF device controls pancreatic cancer cells without any damage to nearby cells, or normal tissues and organs. We still have a lot of work to do but this is an important proof of principle.?
Relevance
Gold colloids have a long history of minimal adverse effects, whereas nonionizing radiation is known to be safe. Therefore the researchers believe that nanoparticle-mediated hyperthermic therapy offers a treatment that may have a more direct action on pancreatic cancer cells and have less adverse effects than systemic chemotherapy.
Mark Neidig, Executive Director of Kanzius Cancer Research Foundation noted: ?These recent findings bring us one step closer to our goal of producing an effective, noninvasive cancer treatment that doesn?t have the side effects associated with current treatments like chemotherapy and radiation.? Future studies include the development of an orthotopic model as well as the investigations of micrometastatic disease.
References:
[1] Glazer ES, Zhu C, Massey KL, Thompson CS, Kaluarachchi WD, Hamir AN, Curley SA. Noninvasive Radiofrequency Field Destruction of Pancreatic Andenocarcinoma Xenografts Treated with Targeted Gold Nanoparticles. Clin Cancer Res. 2010 Dec 1;16(23):5712-21. [Full Article]
[2] National Cancer Institute, U.S. National Institutes of Health – Pancreatic Cancer (Last accessed on January 12, 2011)
[3] – National Cancer Insti
tute, U.S. National Institutes of Health – Pancreatic Cancer Types (Last accessed on January 12, 2011)
[4] Ghaneh P, Costello E, Neoptolemos JP (August 2007). Biology and management of pancreatic cancer. Gut 56 (8): 1134?52. doi:10.1136/gut.2006.103333. PMID
[5] Merck Manual. Pancreatic Cancer. (Last accessed on January 12, 2011)
[6] Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin. 2000 Jan-Feb;50(1):7-33.
[7] National Cancer Institute General Information about Pancreatic Cancer Pancreatic treatment(Last accessed on January 12, 2011)
[8] Pancreatic Cancer Action Network. Learn About Pancreatic Cancer. Types of Pancreatic Cancer (Last accessed on January 12, 2011)
[9] National Cancer Institute What you need to know about?. Cancer of the Pancreas. (Last accessed on January 12, 2011)
[10] Yeo CJ, Cameron JL, Lillemoe KD, et al.: Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg 221 (6): 721-31; discussion 731-3, 1995.
[11]Conlon KC, Klimstra DS, Brennan MF: Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg 223 (3): 273-9, 1996
[12] Yeo CJ, Abrams RA, Grochow LB, et al.: Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 225 (5): 621-33; discussion 633-6, 1997.
[13] Tabernero J, Van Cutsem E, D?az-Rubio E, Cervantes A, Humblet Y, Andr? T, Van Laethem JL, Souli? P, Casado E, Verslype C, Valera JS, Tortora G, Ciardiello F, Kisker O, de Gramont A. Phase II trial of cetuximab in combination with fluorouracil, leucovorin, and oxaliplatin in the first-line treatment of m etastatic colorectal cancer. J Clin Oncol. 2007 Nov 20;25(33):5225-32. [Full Article]
[14] National Cancer Institute Pancreatic Cancer Treatment Treatment Option Overview (Last accessed on January 12, 2011)
Photo ? Copyright 2011: PRNewsFoto/Kanzius Cancer Research Foundation.
Illustration courtesy of the American Society of Clinical Oncology (ASCO)
