Lung Cancer Patients' Response To Chemotherapy Clearly Predicted By FDG-PET Imaging
Main Category: Lung CancerAlso Included In: MRI / PET / Ultrasound
Article Date: 15 May 2007 - 19:00 PDT
An earlier indication of whether chemotherapy benefits non-small cell lung cancer patients - provided by positron emission tomography (PET) imaging - can guide doctors in offering them better care, according to researchers in the May Journal of Nuclear Medicine.
"Our study demonstrates that patients who respond to chemotherapy can be identified early in the course of their treatment, and these patients will generally exhibit prolonged overall survival," explained Claude Nahmias, professor of radiology and medicine at the University of Tennessee Medical Center in Knoxville. "Although we studied a relatively small number of patients - and our results should be interpreted with caution - it is clear that a repeat PET study with the radiotracer fluorodeoxyglucose (FDG) at the end of the first cycle of chemotherapy would allow the identification of those patients for whom the therapy was futile," he said. "The ability to provide an early indication of therapeutic response has the potential to improve patient care by identifying those patients who do not benefit from their current treatment," explained Nahmias. "Patients would benefit from either having chemotherapy and its associated toxic side effects stopped or going on to a different, and hopefully more adequate, therapeutic approach," added the co-author of "Time Course of Early Response to Chemotherapy in Non-Small Cell Lung Cancer Patients With 18F-FDG PET/CT."
Non-small cell lung cancer is the most common type of lung cancer, usually growing and spreading more slowly than small cell lung cancer. Lung cancer is the second most common cancer and the most common cause of cancer-related death in both men and women in the United States. In 2007, about 213,380 new cases of lung cancer (both small cell and non-small cell) are expected in the United States, and about 160,390 people will die of this disease. For most patients with non-small cell lung cancer, current treatments do not cure the cancer.
"With non-small cell lung cancer - since the relatively modest increase in survival must be balanced against the toxicity of the chemotherapeutic treatment - the case for monitoring therapeutic response is especially compelling," said Nahmias. "To assess the response to chemotherapy in patients with advanced non-small cell lung cancer, all of the studies published thus far have evaluated the patients at one, or at most two, time points after the initiation of chemotherapy," said Nahmias. "In our study, we evaluated 15 patients weekly - for seven weeks - as they started their chemotherapy regiment. In spite of the persuasive findings of several studies investigating PET for monitoring response to cancer therapy, until now no published reports have clearly demonstrated that PET results were used to alter treatment," he noted.
PET is a powerful molecular imaging procedure that noninvasively demonstrates the function of organs and other tissues. When PET is used to image cancer, a radiopharmaceutical (such as FDG, which includes both a sugar and a radionuclide) is injected into a patient. Cancer cells metabolize sugar at higher rates than normal cells, and the radiopharmaceutical is drawn in higher amounts to cancerous areas. PET scans show where FDG is by tracking the gamma rays given off by the radionuclide tagging the drug and producing three-dimensional images of their distribution within the body. PET scanning provides information about the body's chemistry, metabolic activity and body function.
"Our result - that PET studies one and three weeks after initiation of cancer therapy can predict success or failure of the therapy - should be validated in a larger study in which patients are enrolled with the intention of applying it in patient management," said Nahmias. He added, "I am forever grateful to all the patients who came back week after week to undergo our PET scans."
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"Time Course of Early Response to Chemotherapy in Non-Small Cell Lung Cancer Patients With 18F-FDG PET/CT" appears in the May issue of the Journal of Nuclear Medicine, which is published by SNM, the world's largest molecular imaging and nuclear medicine society. Other co-authors are Wahid T. Hanna, Misty J. Long, Karl F. Hubner and David W. Townsend, departments of Medicine and Radiology, University of Tennessee, Knoxville, and Lindi M. Wahl, Department of Applied Mathematics, University of Western Ontario, London, Canada.
About SNM - Advancing Molecular Imaging and Therapy SNM is an international scientific and professional organization of more than 16,000 members dedicated to promoting the science, technology and practical applications of molecular and nuclear imaging to diagnose, manage and treat diseases in women, men and children. Founded more than 50 years ago, SNM continues to provide essential resources for health care practitioners and patients; publish the most prominent peer-reviewed journal in the field (the Journal of Nuclear Medicine); host the premier annual meeting for medical imaging; sponsor research grants, fellowships and awards; and train physicians, technologists, scientists, physicists, chemists and radiopharmacists in state-of-the-art imaging procedures and advances. SNM members have introduced - and continue to explore - biological and technological innovations in medicine that noninvasively investigate the molecular basis of diseases, benefiting countless generations of patients. SNM is based in Reston, Va.; additional information can be found online at http://www.snm.org/.
Contact: Maryann Verrillo
Society of Nuclear Medicine
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Pet Imaging Vs. Cell Culture Assay
posted by Gregory D. Pawelski on 18 May 2007 at 10:53 pmPossible indications of whether chemotherapy benefits NSCLC patients could be provided by PET imaging. PET scans during cancer treatment can show whether chemotherapy is working, allowing doctors to adjust dosages or to halt ineffective chemotherapy, which has highly unpleasant toxic side effects.
However, the biggest problem with that method is you give the patient potentially toxic and ineffective drugs and wait six to eight weeks and then make tumor measurements. And then give more potentially toxic and ineffective drugs and wait another six to eight weeks and repeat measurements (drastically adding to costs).
You still have the patient getting potentially toxic and ineffective treatment and then you still have to wait weeks until you could try Plan B. You measure the drug effects on tumors in the patient (one treatment at a time), rather than in the laboratory (a less costly method) where as many as twenty treatments can be done to see which one works best.
The mutagenic effects of the wrong chemo from the start can begin the chain of metastatic events. A chemo-induced gene mutation can happen when the original chemo received does not work. The cancer comes back. When it does this, the tumor comes back more aggressively. The mutagenic effects of chemotherapy on a genetically-unstable tumor, drives the tumor into a state of more aggressive behavior. You might kill off a whole lot of cancer, only to cause a mutation in the remaining cancer, such that the remaining cancer behaves in a more aggressive fashion.
Cell culture assay results of "fresh" tumor (not passaged) specimens have shown that tumor cell clusters treated with a drug sometimes take up copious amounts and sometimes have taken up little or none. With a cell culture assay, it is possible to see which cells have taken it up and which haven't.
Drug resistance/response is multifactorial. It matters not that a particular intracellular molecular target is present, if the drug can't even get into the cell to interact with that target or if it gets in but is metabolized or actively extruded out of the cell (a common mechanism of drug resistance). What is measured with the EGFRx Assay is the net result of everything.
It is not known why a drug either works or doesn't work. The advantage of the EGFRx Assay is that there is a good idea of what will happen. The disadvantage is that it is not known why the drug worked or why it didn't work, only that it worked. The EGFRx Assay uses a combination of the morphologic endpoint (DISC) and one or more of the metabolic endpoints (MTT, ATP, resazurin) to test the targeted molecular drugs.
Something more elemental can be going on with the "individual" patient. Does the drug even enter the cell? Once entered, does it immediately get metabolized or pumped out, or does it accumulate? Some clones of tumor cells don't accumulate these drugs. These cells won't get killed by it. The assay measures the net effect of everything which goes on - Whole Cell Profiling. The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. Are the cells ultimately killed, or aren't they?
Each of the new targeted drugs are not for everybody. According to the National Cancer Institute, those who benefit substantially from "targeted" drugs is approximately 10% to 20%. What if you are one of those few? This kind of technique exists today and might be very valuable, especially when active chemoagents are limited in a particular disease, giving more credence to testing the tumor first (rather than by trial-an-error).
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