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Clinical Notes

doi: 10.1097/01.COT.0000346861.92488.d0
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ASTRO Changes Name to American Society for Radiation Oncology

The American Society for Therapeutic Radiology and Oncology has changed its name to the American Society for Radiation Oncology. The new logo keeps the acronym ASTRO by having the “T” represent the new tagline of “Targeting Cancer Care.”

This is the fourth time the Society has changed its name since it was established in 1958 as the American Club of Therapeutic Radiologists.



“Today, most departments and practices use the term ‘radiation oncology’ to represent the hard work they do using radiation therapy to treat and cure patients with cancer,” ASTRO CEO Laura I. Thevenot, said in a news release.

“Over the past few decades the term ‘therapeutic radiology’ has become outdated and confusing as radiation oncology has evolved into a specialty very separate from its origins in diagnostic radiology. ASTRO's new name will better correlate with the term that our members are using in their own practices to communicate with patients and better reflect who we are as a specialty.”

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Mucin Found as Barrier to Pancreatic Cancer Drugs

The thick layer of mucin covering pancreatic cancer cells acts as a barrier to chemotherapeutic drugs, like fluorouracil (5-FU), a study from Northeastern University has shown.

Robert B. Campbell, PhD, and his PhD student Ashish V. Kalra have found not only that reducing the mucin on the tumor cell's surface increases the effect of the drug significantly, but that it may also contribute to a decrease in the amount of drug needed to get the same therapeutic result.

“We are beating down the barrier that stands in the way of effective cancer treatment,” said Dr. Campbell, Assistant Professor of Pharmaceutical Sciences at Northeastern's Bouvé College of Health Sciences. “Our goal is to help improve the efficacy of drugs and limit the amount of these toxic drugs needed for treatment.”

This is the second phase of the two researchers' study of the biological attributes of pancreatic tumor cells and the role cellular barriers play in limiting the effectiveness of drugs. It was found in Phase I that extracellular-bound mucin impedes the cytotoxic effect of 5-FU against the growth of pancreatic cancer cells in vitro.

Now in Phase II of the study, published in the January issue of the European Journal of Cancer, the researchers confirmed that the mucin glycation mesh produced during the normal development of pancreatic tumors limits the overall effectiveness of 5-FU in vivo. It was also shown that the concentration of 5-FU taken up by the target cell was five times greater when the formation of the glycation mesh was inhibited, further supporting the barrier effect of mucin.



“We knew from the first study that the ability of pancreatic cancer cells to respond to 5-FU treatment in vitro can be enhanced by inhibiting mucin o-glycosylation,” Dr. Campbell said. “This time, we found that the overall tumor response to 5-FU in mice that received intratumoral injections of the mucin O-glycosylation inhibitor was greater than the saline control group.”

The team also confirmed that the exposure to mucin inhibitors did not harm the viability and morphology of the pancreatic cancer cells.

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NHL: After CHOP-14-R, Radiotherapy to Bulky Disease Found to Benefit Some Patients

Combined data from two prospective studies by the German High-Grade Non-Hodgkin-Lymphoma Study Group (DSHNHL) of elderly patients receiving six cycles of CHOP-14 plus rituximab found that adding radiotherapy for bulky disease offers no benefit to patients who achieved a complete response after completion of immunochemotherapy. But for patients with bulky disease who achieved only a partial response after immunochemotherapy, additional radiotherapy did improve outcomes.

Michael Pfreundschuh, MD, PhD, Director of Internal Medicine Clinic I in Homburg-Saar, Germany, presented data at the ASH Annual Meeting from the RICOVER60 trial and from a follow-up trial.

The RICOVER60 trial showed that six cycles of CHOP-14 with rituximab (R-CHOP-14) was superior to eight cycles of R-CHOP-14, to six cycles of CHOP-14, and to eight cycles of CHOP-14, in elderly patients with CD20-positive aggressive lymphoma (Pfreundschuh M: Lancet Oncol 2008;9:105–116).

The prospective follow-up trial studied the effects of six cycles of R-CHOP-14 without radiotherapy in 166 elderly patients, compared with 306 patients from RICOVER60 who received six cycles of R-CHOP-14 plus radiotherapy to bulky disease.

A total of 164 of the patients were evaluable, with a median observation time of 17 months. The median age in the without-radiotherapy study arm was older than in the with-radiotherapy arm (age 71 vs 69). The without-radiotherapy group also had more patients whose disease was in advanced stages (60% vs 50%), and more with extranodal involvement (63% vs 53%).

But bulky disease was more frequent in the patients receiving the added radiotherapy (38% vs 29%).



Dr. Pfreundschuh said adherence to the immunochemotherapy protocol was excellent in both studies, with median relative rituximab and cytotoxic drug doses of 99%.

The overall response rate to therapy was similar in the two studies: The complete and unconfirmed complete response rate was 76% without radiotherapy vs 78% with radiotherapy; disease progression was 5.5% vs 6.5%; relapses after the responses were 8% vs 10%; and therapy-associated deaths were 7% vs 6%.

However, patients who received additional radiotherapy to bulky disease had a 25% better 18-month event-free survival rate (68% vs 43%), 10% better progression-free survival (77% vs 67%), and 4% better overall survival (80% vs 76%) compared with patients who received R-CHOP-14 but no radiotherapy.

He noted that the lower event-free survival rate in the without-radiotherapy arm was due to patients with bulky disease not achieving a complete or unconfirmed complete response after six cycles of R-CHOP-14. But patients in complete or unconfirmed complete response after R-CHOP-14 who had bulky disease fared equally well whether they did or did not receive additional radiotherapy—the event-free survival rates at 18 months were 84% vs 86%.

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New Understanding of How Anthracyclines Block Blood Vessel Growth, Slow Cancer Spread

Researchers at Johns Hopkins University School of Medicine have discovered how anthracyclines can block angiogenesis. The findings, reported in Proceedings of the National Academy of Sciences, suggest that there might be a subgroup of cancer patients particularly sensitive to anthracyclines.

The standard method of administration of doxorubicin, daunorubicin, epirubicin, and idarubicin has been to use the highest tolerable dose every few weeks to kill all rapidly growing cells by preventing them from accurately copying their genetic material.

“But the late Judah Folkman discovered in 2000 that so-called metronomic treatment, giving patients lower doses of these drugs more frequently, can keep cancer growth at bay by blocking blood vessel formation, but the exact mechanism by which this occurred wasn't known,” Gregg L. Semenza, MD, PhD, Director of the Vascular Program at Johns Hopkins' Institute for Cell Engineering and a member of the McKusick-Nathans Institute of Genetic Medicine, noted in a news release.

“Now we've shown how it happens and what players are involved, which could help shape future clinical trials for patients with certain types of cancers.”

Dr. Semenza and his team have long studied how the hypoxia-inducible factor (HIF-1), protein helps cells survive under low-oxygen conditions. HIF-1 turns on genes that enhance angiogenesis to help oxygen-starved cells, like those found in fast-growing solid tumors, survive.

To look for drugs that can prevent new blood vessel growth, the team tested more than 3,000 already FDA-approved drugs in the Johns Hopkins Drug Library for their ability to stop HIF-1 activity. Using modified liver cancer cells growing in low oxygen, the team treated cells with each of the drugs in the library and examined whether the drug could stop HIF-1 from turning on genes.

Daunorubicin was found to reduce HIF-1's gene-activating ability by more than 99%. Since to turn on genes, HIF-1 has to bind to DNA, the researchers looked at drug-treated and untreated cells and compared regions of DNA known to be bound by HIF-1.



The sites that are bound by HIF-1 in untreated cells were unbound in anthracycline treated cells. “We know that this class of drug prefers to bind to DNA sequences that are similar to the DNA sequence bound by HIF-1, but this is the first direct evidence that anthracyclines prevent HIF-1 from binding to and turning on target genes,” Dr. Semenza said.

To see if the interference with HIF-1 binding to DNA affects cancer growth, the team grew tumors in mice from human prostate cancer cells, treating the mice with daunorubicin, doxorubicin, or saline once a day for five days. Tumors in the saline-treated mice nearly doubled in size in that time, whereas tumors in the drug-treated mice stayed the same or became smaller.

When tumors from drug-treated mice were examined, the number of blood vessels was dramatically reduced compared with those in mice treated with saline. Additional tests showed that the genes that HIF-1 turns on to drive blood vessel formation were turned off in tumors from the drug-treated mice.

“What this means, we hope, is that patients with a prostate cancer that has high HIF-1 levels—which puts them at greater risk of relapse following surgery or radiation therapy—might benefit from treatment with these drugs,” Dr. Semenza said. “However, clinical trials are necessary to determine whether this approach will help keep cancer patients alive.”

The research was funded by the Flight Attendant Medical Research Institute and Johns Hopkins Institute for Cell Engineering.

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Scattered Light Rapidly Detects Tumor Response to Chemotherapy

New technology developed by Duke University can help clinicians more precisely detect whether specific cancer drugs are working, and should give basic researchers a new tool to better understand the underlying mechanisms of cancer development.

By interpreting how beams of light scatter off of tumor cell samples, researchers can determine if cancer cells are responding to chemotherapeutic agents within a matter of hours.

“The new technology allowed us to detect the tell-tale signs of apoptosis in human breast cancer cells in as little as 90 minutes,” said the senior researcher of the study published in the February issue of Cancer Research, Adam Wax, PhD, Associate Professor of Biomedical Engineering. “Currently, it can take between six and eight weeks to detect these changes clinically. It appears that this approach has the potential to be helpful in both clinical and laboratory settings.”

The light-scattering technology is known as angle-resolved low coherence interferometry (a/LCI). As explained in a news release, light is shined into a cell sample and sensors capture and analyze the light as it is scattered back. The technique is able to provide representations of sub-cellular structure without disrupting the cells, and can be used to scan a large number of cells in a short time.

“Now, oncologists typically judge if a chemotherapeutic agent is working by looking for shrinkage in the tumor using imaging techniques, such as MRI or PET, or pathological response at time of surgery” said Julie Ostrander, PhD, a molecular cancer biologist at Duke, who along with Duke bioengineer Kevin Chalut were the paper's first authors. The research was supported by the National Science Foundation, National Institutes of Health, and Department of Defense.

“If we had a way to detect early on in the apoptotic process whether or not a drug was working, patients would not have to wait weeks to months to find out,” Dr. Ostrander said. “The idea that you could shine a light at a tumor and use the light-scattering pattern to measure the success of drugs is a big step forward.”

In the laboratory study, human breast cancer cells were exposed to doxorubicin and paclitaxel, and using the a/LCI technology, the researchers looked for specific patterns, which indicate that structural changes have occurred.

Figure. Ce

Figure. Ce

When compared with control cells, the paclitaxel-treated cells began showing significant increases in a pattern called fractal dimension within 90 minutes. Doxorubicin-treated cells exhibited the same increases within three hours. Interestingly, Dr. Wax said, the fractal dimensions began decreasing at six hours, only to increase again within 12 hours of treatment.

“The fact that the changes in structure appear over two distinct time scales suggests that multiple mechanisms are involved in these early events in apoptosis. Further analysis showed the early changes we observed were taking place in the mitochondria, while the changes in the structure of the nucleus were responsible for the later ones.”

Dr. Wax and colleagues at the University of North Carolina at Chapel Hill are now conducting a pilot clinical trial in humans using a similar technology for early detection of Barrett's esophagus.

© 2009 Lippincott Williams & Wilkins, Inc.
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