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Karmanos Cancer Center Reports On Two Advances

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Scientists from the Barbara Ann Karmanos Cancer Institute and Wayne State University School of Medicine in Detroit are presenting two research studies that found the use of Fast Neutron Radiotherapy — a form of radiation that is about three times more powerful than typical photon radiotherapy — is highly effective and safe for patients who are dealing with non-small cell lung cancer.

The findings are being formally presented Monday, Nov. 1, at the American Society of Therapeutic Radiology and Oncology Annual Meeting.

Also Sunday, at the same meeting, Karmanos researchers will present data that suggests low levels of pre-treatment radiation mimicking the doses delivered by CT scans for image guidance pose no risk to the efficacy of radiotherapy in patients with prostate carcinoma and non-small cell lung carcinoma.

George G. Chen, M.D., chief resident of Radiation Oncology at Karmanos and the Wayne State school, is giving the poster presentations on the two research projects titled, “Salvage Fast Neutron Radiotherapy for Treatment of Refractory Non-Small Cell Lung Cancer” and “Fast Neutron Radiotherapy for Advanced Stage Non-Small Cell Lung Cancer.”

Fellow authors are fourth-year medical student Laura Koller, as well as members of Karmanos and WSU SOM’s Department of Radiation Oncology, including Peter Paximadis, M.D.; Professor Michael Joiner; Jay Burmeister, chief of physics; and Andre Konski, M.D., professor and chair of the Department of Radiology and clinical service chief of Radiation Therapy. Other authors from Karmanos are Shirish M. Gadgeel, M.D., leader, Thoracic Oncology Multidisciplinary Team; Antoinette Wozniak, M.D., member of the Thoracic Oncology Multidisciplinary Team; and Frank Baciewicz, M.D., professor of surgery.

Researchers analyzed results for non-small cell lung cancer patients that were treated at Karmanos from 1993 to 2006. Treatments included a combination of fast neutron and photon radiotherapy. 

“The main point of our research was to determine which patients could benefit from FNRT,” said Dr. Chen. “We found we could deliver FNRT safely at certain dose levels, which we had to translate from fast neutron radiation doses to photon radiation doses.”

Delivering FNRT takes great skill considering it comes with risks, Dr. Chen said, including potential for higher levels of toxicity. FNRT lost favor in the medical community in the past because in some cancer patient cases, delivering FNRT resulted in higher toxicities.

Researchers at Karmanos and Wayne State said that it’s critical to understand and use the most effective and safest doses to provide the best outcomes for patients who can benefit from both photon and neutron radiotherapies. While FNRT can help many cancers, it seems to work best on lung cancer, sarcomas, glioblastomas (brain cancers), prostate cancer and head and neck cancers.

In the FNRT study for salvage therapy, 20 patients with non-small cell lung cancer had failed primary treatment with chemotherapy or radiotherapy. The estimated clinical relative biological effectiveness for neutron radiotherapy was three times more effective than photon radiotherapy in the normal lung tissue and four times more effective for targeted tumors. In the study group, researchers found there were no grade three or four toxicities, which usually require significant medical intervention or hospitalization. All treatment related toxicities, such as radiation pneumonitis, esophagitis and radiation dermatitis were adequately treated in an outpatient basis.

Among the 12 patients who had longer than a one-month follow up, six patients had no evidence of local cancer progression. The median local control of the other six patients that did have cancer recurrence was three months. Nine out of the 14 symptomatic patients had successful palliation within a month after treatment was over. One year overall survival was 20 percent, and one year disease-free survival was 10 percent.

For the study of FNRT for advanced stage non-small cell lung cancer, Chen and his co-authors looked at the results of 23 patients who received a combination of FNRT and photon radiotherapy for non-small cell lung cancer between March 1993 and December 2006.

As for the study being presented Sunday, Iftekhar U. Ahmad, M.D., a former radiation oncology resident at Karmanos and the Wayne State University School of Medicine, is lead author of the study titled, “Effect of Pre-Treatment Imaging Dose on the Radiosensitivity of Tumor Cells” and will present the findings at ASTRO. Dr. Ahmad is now a staff radiation oncologist at OSF Saint Anthony Medical Center in Rockford, Ill.

Fellow authors from Karmanos and Wayne State include Vinita Singh-Gupta, member of the Department of Radiation Oncology; Christopher Yunker, research assistant with Karmanos; Jay Burmeister, chief of physics; Michael C. Joiner, professor and program leader of radiation oncology; and Gilda G. Hillman, associate professor in radiation oncology.

Ahmad said that imaging of patient anatomy using CT scans is routinely performed immediately prior to radiation therapy to provide information on soft tissue differentiation and to confirm localization of external beam radiation delivery to the tumor. Karmanos’ study built upon the findings of a recent University of Virginia study that suggested that such pre-treatment doses of radiation caused the cancer cells to have higher survival rates.

“Our question was, is this real?” he said. “The doses they used to mimic their CT scan doses were higher than image guided dose data published in the literature. Our dose was less than half of what they used. We felt this was more realistic as to what is delivered in routine clinical care of patients with prostate and lung cancer. The goal of this study was to determine whether these low doses of radiation used for image guidance prior to therapeutic doses affects radiation therapy efficacy for prostate carcinoma and non-small cell lung carcinoma cells and to determine the influence of the time gap between image guidance and treatment.”

Karmanos researchers used the PC-3 PCa and A549 NSCLC human tumor cell lines for the study, similar to cell lines used in University of Virginia’s study. All radiation was delivered using a Pantak orthovoltage unit. Karmanos researchers used a dose of two centigray units of absorbed radiation to mimic a CT scan and doses were administered at intervals of two, five and eight minutes.

After simulated CT doses were given, researchers then used increased levels of radiation therapy doses in the prostate and lung cancer cell lines.

Control groups included non-irradiated cells and cells irradiated only with radiation therapy doses between two and eight gray units. Treated cells were tested in triplicate. Plating efficiency — the measure of the number of colonies originating from single cells — was determined for each sample and the surviving fraction was calculated by normalizing each test PE and control PE for non-irradiated cells. Researchers also assessed damage to the cells on a molecular level.

Based on results, the study suggests that low doses of radiation for daily pre-treatment positioning prior to radiation therapy do not affect the human prostate carcinoma and non-small cell lung carcinoma cell lines.

“If we’re giving between 30-40 treatments to a patient and imaging them prior to treatment every day, we wanted to know how this is affecting how well we treat the cancer and how much extra radiation is being delivered to the patient,” said Dr. Ahmad. “Any time you irradiate at any dose, there is going to be some response by the cell.

“In this study, we didn’t see any changes in the cancer cell survival rate due to the administration of doses typical for pre-treatment imaging. We also didn’t see any changes whether you quickly treat the patient after the pre-treatment dose or if you wait, for example, eight minutes.”

The Karmanos Cancer Institute and Wayne State recently took delivery of three new top-of-the-line Varian linear accelerators, located at the Institute’s sites in Detroit, Rochester Hills and Farmington Hills. Andre Konski, M.D., chairman of the Department of Radiation Oncology, says that radiation technology is improving so rapidly that staff must remain highly trained to ensure accuracy.

“Doing research is only one part of establishing best practices when using sophisticated radiotherapy equipment,” said Dr. Konski. “It isn’t enough to have the most advanced technology at our disposal. Through these in-depth, retrospective studies, we are able to determine the safest and most effective methods in treating our patients.”

More at www.karmanos.org .    

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