Lung Cancer and Smoking Cessation

[gpawelski]

Since a substantial number of patients presenting with lung cancer either smoked in the recent past or continue to do so, it is important to make sure that the patient stops smoking as soon as possible to improve their treatment outcome. the emphasis should be on improvement of treatment outcome and future health improvement.

There are guidelines regarding smoking cessation techniques that have resulted from reviews of the world's literature and are very well accepted throughout the medical and psychological fields. However, the biggest problem remains in having healthcare providers implement them routinely. Most have emphasized the role of the primary healthcare provider in providing smoking cessaton advice to patients, whereas the specialists, such as medical oncologists, radiation oncologists, thoracic surgeons or pulmonary care specialists should be dealing with the health problems resulting from the smoking as the patient faces imminent interventions such as radiation therapy, chemotherapy or surgery.

Since ongoing smoking may significantly affect the outcome of subsequent surgery or therapy and negatively impact long-term survival, it is now the specialists' turn to provide the urgent smoking cessation treatment. Besides providing evaluation and management services, making referrels for diagnostic testing, radiation therapy, surgery and other procedures as necessary, and offer any other support needed to reduce patient morbidity and extend patient survival, I certainly hope they add smoking cessation guidance and support.

No pharmaceutical trial ever followed whether patients smoked during their clinical trials, despite dosing themselves daily with cigarettes with thousands of chemicals in them. The addition of nicotine inhibits the ability of a chemo drug (like etoposide) to induce apoptosis by 61%. If a drug like nicotine, which occurs in the highest concentration of any drug in a cigarette, inhibits the ability of a major chemotherapy drug by 61%, a medical oncologist should care if it was being ingested during treatment.

www.treatobacco.net is an evidence-based site containing information in 11 languages on tobacco dependence treatment relative to efficacy, safety, demographics and health effects, health economics, and policy.

www.cdc.gov/tobacco/ is a site to let you know everything you wanted to know about tobacco at the CDC.

www.guideline.gov/summary/summary.aspx?doc_id=2958&nbr=2184 is the National Guideline Clearinghouse web site for smoking cessaton.

Since a substantial number of patients presenting to a cardiothoracic surgery clinic either smoked in the recent past or continue to do so, it is important to make sure that patients stop smoking as soon as possible to improve their treatment outcome. The emphasis should be on improvement of treatment outcome and future health improvement. Reinforcing the guilt feelings the patient may already have is counterproductive, and is a significant concern of patient and patient advocacy groups at the present time.

www.ctsnet.org/sections/clinicalresources/thoracic/expert_tech-25.html

[gpawelski]

The new genomic test - Lung Metagene Predictor - is supposed to tell physicians which lung cancer patients will benefit from chemotherapy and which ones do not need to be unnecessarily exposed to toxic chemotherapy cocktails.

The test doesn't predict which patients will benefit from chemotherapy (i.e. which patients are chemosensitive). Rather, it's like the Oncotype Dx test, which identifies patients who are unlikely to have a recurrence if treated with surgery alone. If you aren't going to have a recurrence, you don't need chemotherapy.

The test doesn't do anything to indicate if chemotherapy would or would not be helpful for those patients at higher risk for recurrence, much less which chemotherapy would be most likely to be helpful. Also, the test has a 10% false reassurance rate (10% of the good prognosis patients none the less recurred).

A genomic test can help to find out if a cancer patient will benefit from chemotherapy or not, and if they do, Whole Cell Profiling can help see what treatments have the best opportunity of being successful. Other tests, such as those which identify DNA, or RNA sequences or expression of individual proteins often examine only one component of a much larger, interactive process.

Whole Cell Profiling (via Cell Function Analysis) measures the response of the tumor cells to drug exposure. Following this exposure, they measure both cell metabolism and cell morphology. 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. No matter which genes are being affected, Whole Cell Profiling is measuring them through the surrogate of measuring if the cell is alive or dead.

For example, the epidermal growth factor receptor (EGFR) is a protein on the surface of a cell. EGFR inhibiting drugs certainly do target specific genes, but even knowing what genes the drugs target doesn't tell you the whole story. Both Iressa and Tarceva target EGFR protein-tyrosine kinases. But all the EGFR mutation or amplificaton studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack.

It doesn't tell you if Iressa is better or worse than Tarceva or other drugs which may target this. There are differences. The drugs have to get inside the cells in order to target anything. So, in different tumors, either Iressa or Tarceva might get in better or worse than the other. And the drugs may also be inactivated at different rates, also contributing to sensitivity versus resistance.

One of the most promising new approaches that may deal with early detection of cancer is called Proteomics (Protein Expression Analysis), the study of proteins in the cells, tissues and body fluids. Even before a tumor can be felt, some researchers have found, the tumor begins secreting a distinctive pattern, or fingerprint of proteins. Here, you go beyond genes (DNA, the Genomic Analysis or structure of the human genome) and beyond Gene Expression (the measure of RNA content, like Her2/neu in breast cancer) to measure the actual proteins themselves.

Genomic Analysis is only important insofar as it influences Gene Expression Analysis, which is only important insofar as it influences Protein Expression Analysis (Proteonomics), which is only important insofar as it influences Protein Function Analysis (are proteins active or inactive), which is only important insofar as it influences Cell Function Analysis (cell culture testing), which is only important insofar as it influences Disease Analysis (doing something to treat the patient and then making a measurement on the patient with CT/PET scanning), in that order. There is an inverse hierachy between relevance and ease of measurement.

There are many pathways to altered cellular (forest) function (hence all the different "trees" which correlate in different situations). It serves to validate Whole Cell Profiling. The forest is looked at, and not the trees. Whole Cell Profiling measures what happens at the end (the effects on the forest), rather than the status of the individual trees. Cancer is a complex disease and needs to be attacked on many fronts. The best thing to do is to combine these different tests in ways which make the most sense. The future of cancer therapy will be personalized treatments for individual patients, and will require a combination of novel diagnostics and therapeutics.

Improving cancer patient diagnosis and treatment through a combination of cellular and gene-based testing will offer predictive insight into the nature of an individual's particular cancer and enable oncologists to prescribe treatment more in keeping with the heterogeneity of the disease. The biologies are very different and the response to given drugs is very different.