· I-Response Solution Used in Prostate Cancer Study
· Treating What the Surgeon Cannot
· PET Imaging Identifies Aggressive Kidney Cancers Requiring Surgery

I-Response Solution Used in Prostate Cancer Study

A study published in the April 15 issue of the journal Cancer Research, entitled “An Imaging Biomarker of Early Treatment Response in Prostate Cancer That Has Metastasized to the Bone,” used a technique called functional diffusion mapping (fDM) to visualize cancer that had spread from the prostate to the bone by measuring the movement of water within tumors. The study tracked the diffusion of water through cells over the course of treatment; as tumor cells die, water diffusion increases because tumor cells slow the movement of water.

In use over the course of the study was the I-Response imaging workstation solution from Cedara Software Corp, Mississauga, Ontario. The researchers at the University of Michigan Comprehensive Cancer Center, Ann Arbor, who authored the Cancer Research study are also aiding Cedara in its development of the system. Study author Brian D. Ross, PhD, professor of radiology and biological chemistry at U-M, noted that there is currently no way to detect bone tumor response to therapy; the functional diffusion map made possible by combining MRI scans with the I-Response workstation could serve as an early biomarker indicating that a cancer is responding to treatment.

“Because water within tumor cells is in a restricted environment relative to extracellular water, loss of cell membrane integrity and cellular density during therapy will be detected by fDM as an increase in diffusion,” the study’s authors wrote. “Regions of significantly increased diffusion values were detected early using fDM in docetaxel- treated versus untreated metastatic prostate bone tumors at 7 days post-treatment initiation, indicating loss of tumor cell viability. Validation of fDM results was accomplished by histologic analysis of excised tissue. Results from this study show the capability of fDM as a biomarker for detection of bone cancer treatment efficacy, thus warranting clinical evaluation.”

Cedara Software plans to soon make the I-Response solution available to OEMs to incorporate into their product offerings.

?C. Vasko

Treating What the Surgeon Cannot

Intraoperative radiation therapy moves into the OR

Sometimes, a tumor cannot be completely removed through surgery. It is attached to healthy tissue or too small to see. But intraoperative radiation therapy (IORT) can be used to treat what the surgeon can’t. Today’s electron beam technology is able to deliver a fairly straight shot of radiation?the equivalent of 2 to 3 weeks of conventional radiation therapy?directly onto the remaining organ or tissue to attack microscopic residual tumors. And more recent advances make that possible right in the operating room.

According to IntraOp Medical Corp, Sunnyvale, Calif, IORT was first introduced in 1906. Throughout its early development, the technique took too long, produced inconsistent results, and was subsequently abandoned. The advent of electron beam technology in the 1960s eliminated some of these initial problems, limiting penetration and increasing dose speed. However, the machines were very heavy and required 100 tons of shielding as well as a multimillion-dollar investment, according to Donald Goer, PhD, president and CEO of IntraOp Medical. Patients, therefore, had to be brought to the radiation facility.

The transportation of patients from surgery to the radiation facility and back to surgery created new problems, involving time, resources, and safety issues. “It can add somewhere between 1 and 2 hours to the procedure, making it difficult to justify,” Goer said. Bringing the technique into the operating room could be expected to eliminate these challenges, potentially broadening IORT’s applications.

With this goal, IntraOp Medical developed Mobetron, a mobile intraoperative radiation therapy device that weighs 2,700 pounds (“one eighth of a conventional machine,” Goer noted) and does not require shielding. Its use of proprietary 9,000 MHz X-band technology rather than 3,000 MHz S-band to generate the electron beams means the components weigh much less. The elimination of bending magnets reduces the amount of stray radiation. First introduced in 1997 and granted FDA 510(k) clearance in 1998, the machine has been used on more than 30,000 patients.

At the Mayo Clinic, Rochester, Minn, recurrent rectal cancer is the most common disease treated with IORT.1 Recent studies at the institution found improved survival rates in patients with recurrent colon or rectal cancer who underwent IORT compared to those who did not: 19% compared to 7%.1

Other procedures performed at the Mayo Clinic with IORT include recurrent gynecologic cancer, genitourinary cancer, gastrointestinal cancer, soft tissue sarcomas, recurring cancers in lymph nodes, and primary locally advanced cancers with a low likelihood of cure with surgery alone.1 Its value can be seen in recent studies, according to Goer. He cites a pooled analysis under way by the International Society of Intraoperative Radiation Therapy (ISIORT). Results to be released later this year show that 649 European cancer patients, who had undergone IOERT (intraoperative electron radiation therapy) for locally advanced rectal cancer, exhibited 90% 5- and 10-year local control rates. “The conventional approach has resulted in less than 50%,” Goer said.

He suggests more studies may lead to even more applications, and notes ongoing research on IORT’s effect in menopausal women with node-negative small breast cancer tumors, lung cancer patients, and high-risk prostate cancer. Goer describes a study to be released later this year, which examines the use of IOERT during breast lumpectomy. The analysis of 1,100 women?of which 60% or more exhibited adverse factors, such as G3 or higher grade cancer?found that of the women treated with IOERT, only five had a breast cancer recurrence within 4 years (about 0.45%), Goer said.

IORT can also be used to treat skin cancer, although surgery is often not required. The new device’s mobility means it can be moved from the OR to another room to treat skin cancer patients, increasing its justification in smaller facilities. With more studies to prove that IORT can treat what the surgeon can’t, the justification may not be necessary.

?R. DiIulio


  1. Intraoperative radiation therapy at Mayo Clinic. Mayo Clinic. Available at: www.mayoclinic.org/intraoperative-radiation. Accessed May 18, 2007.

PET Imaging Identifies Aggressive Kidney Cancers Requiring Surgery

A study in the April 2007 issue of The Lancet Oncology demonstrates that PET imaging with a radio-labeled antibody accurately identifies whether a patient has clear renal cell carcinoma, the most common and aggressive type of renal tumor. Researchers from Memorial Sloan-Kettering Cancer Center (MSKCC), New York, used the radiolabeled monoclonal antibody G250, which was originally developed as a potential therapeutic agent by one of the study’s authors, Lloyd J. Old, MD, director of the New York branch of the Ludwig Institute for Cancer Research (LICR) and an investigator at MSKCC.

“This work represents the first prospective clinical trial to determine whether PET using a radiolabeled antibody is sensitive and specific enough to permit identification of clear cell renal carcinoma,” said lead author Chaitanya Divgi, MD, chief of nuclear medicine and clinical molecular imaging at the University of Pennsylvania. There were an estimated 38,890 new cases of renal carcinoma in the United States in 2006, and an estimated 12,840 deaths from the disease. Of patients who present with or develop metastatic renal cancer, approximately 90% of tumors have the most common clear cell histological subtype.

G250 has been shown to target and bind to clear cell renal carcinoma and to react against an enzyme that is present in 94% of cancers of this type; renal carcinoma also has the highest recorded tumor uptake for G250 of any solid tumor. In the study, 15 out of 16 clear cell renal carcinomas were correctly identified using G250 PET?for a sensitivity of 94%. The nine patients with non-clear cell renal masses were negative on the PET scan.

Senior author Paul Russo, MD, a urologic cancer surgeon at MSKCC, said, “Anti-body PET could end up changing the standard of care for patients with kidney cancer. The excellent sensitivity and specificity of this tool support the utility of G250 PET imaging in the work-up and management strategies for clinically localized renal masses and as an alternative to biopsy for distinguishing renal lesions.”

The study’s authors believe G250 PET could also be used to measure the therapeutic effects of a particular treatment and to predict the likelihood of recurrence. “The promising results of this trial have stimulated interest in a larger, prospective multi-center trial to confirm our findings, and ultimately greatly improve the clinical management of patients with kidney tumors,” Divgi said.

?C. Vasko