Monthly Archives: September 2004

Matched-Pair Analysis of Survival of Never Smokers and Ever Smokers With Squamous Cell Carcinoma of the Head and Neck

  • 9/30/2004
  • Kristen B. Pytynia et al.
  • Journal of Clinical Oncology, Vol 22, No 19, 2004: pp. 3981-3988

PURPOSE
To compare survival rates between patients with squamous cell carcinoma of the head and neck (SCCHN) without a history of smoking (never smokers) and those with a current or previous history of smoking (ever smokers).

PATIENTS AND METHODS
Fifty never smokers with newly diagnosed SCCHN were matched to 50 ever smokers according to sex, age, tumor site, overall stage, nodal stage, and treatment. Survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model.

RESULTS
The never smokers had a greater overall survival (P = .020), disease-specific survival (P = .022), and recurrence-free survival (P = .016). Furthermore, matched-pair analysis demonstrated smoking was associated with a significant increase in risk of overall death (relative risk [RR] = 3.50; 95% CI, 1.14 to 10.77; P = .029), risk of death owing to disease (RR = 3.98; 95% CI, 1.11 to 14.33; P = .034), and risk of disease recurrence (RR = 3.29; 95% CI, 1.18 to 9.14; P = .023). Smoking was associated with three-fold increases in risk for overall death, death owing to disease, and recurrence after adjustment for cancer-associated symptom severity and alcohol use, but the 95% CI for these adjusted risk estimates each included the null.

CONCLUSION
Survival differed significantly between never smokers and ever smokers with SCCHN. These results are not substantively explained by differences in cancer-associated symptoms or alcohol use, but the CIs are wide and some imprecision remains. Regardless, possible fundamental differences in SCCHN between ever smokers and never smokers may exist, and further molecular characterization of these tumors is needed to determine whether biologic differences needing targeted therapies exist.

Kristen B. Pytynia, Jonathan R. Grant, Carol J. Etzel, Dianna B. Roberts, Qingyi Wei, Erich M. Sturgis
From The University of Texas M.D. Anderson Cancer Center, Houston, TX

September, 2004|Archive|

Positron Emission Tomography in Combination With Sentinel Node Biopsy Reduces the Rate of Elective Neck Dissections in the Treatment of Oral and Oropharyngeal Cancer

  • 9/30/2004
  • Adorján F. Kovács, Natascha Döbert, Jochen Gaa, Christian Menzel, Klaus Bitter
  • Journal of Clinical Oncology, Vol 22, No 19 , 2004: pp. 3973-3980

PURPOSE
To assess the impact of a diagnostic ladder including [18F]fluorodeoxyglucose positron emission tomography (PET) and lymphoscintigraphy guided sentinel node biopsy (LS/SNB) on neck treatment in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC).

PATIENTS AND METHODS
Prospectively, 62 patients with resectable T1-3 OOSCC underwent computed tomography (CT) and PET. Patients without neck uptake in PET were defined as cN0 and were accrued for LS/SNB. Results were correlated with histopathology. The traditional guidelines according to CT findings were compared to the actual regimen and the outcome.

RESULTS
Sensitivity, specificity, validity, and positive and negative predictive value of PET versus CT were 72% v 89%, 82% v 77%, 79% v 80.5%, 62% v 61.5%, and 88% v 94.5% (not significant). Thirty-eight PET negative patients underwent LS/SNB. Sentinel lymph nodes were found in all 38 patients. Five patients had positive nodes (PET false-negatives) and underwent neck dissection (ND). Fifty-one neck sides in 36 patients who were CT-negative would have been treated with selective ND according to the guidelines, and at least 45 neck sides would have had to undergo extensive ND because of positive CT findings (96 of 124 neck sides). In contrast, PET in combination with LS/SNB spared 59 neck sides, and 41 of 124 neck sides actually underwent ND as a result of PET staging, LS/SNB, and intraoperative decision. After a median follow-up of 35 months, two patients (both cN+ve and pN+ve) suffered from neck relapses.

CONCLUSION
Diagnostics using PET in combination with LS/SNB considerably reduced the number of extensive ND in OOSCC as compared to CT without locoregional hazard.

Adorján F. Kovács, Natascha Döbert, Jochen Gaa, Christian Menzel, Klaus Bitter
From the Departments of Maxillofacial Plastic Surgery, Nuclear Medicine, and Neuroradiology, Johann Wolfgang Goethe-University Medical School, Frankfurt am Main, Germany

September, 2004|Archive|

Cigarette smoke causes breaks in DNA and defects to a cell’s chromosomes

  • 9/30/2004
  • PITTSBURGH, PA
  • William S. Saunders et al.
  • University of Pittsburgh Medical Center

The amount of smoke in just one or two puffs of a cigarette can cause breaks in DNA and defects to a cell’s chromosomes, leading to irreversible changes in genetic information being passed to a newly divided cell, according to University of Pittsburgh researchers. Their findings, to be reported Tuesday, Oct. 5 at the 35th Annual Meeting of the Environmental Mutagen Society, are the first to show that cigarette smoke causes chromosome instability.

While most research has focused on the changes in DNA sequence caused by cigarette smoke, little attention has been given to how smoke affects genomic stability of cells. In laboratory studies using human fibroblasts, common cells found in connective tissue, William S. Saunders, Ph.D., and colleagues discovered that exposure to even a small amount of cigarette smoke condensate – equal to about 1/25 of a cigarette – caused breaks to both strands of DNA and compromised the integrity of the cell’s chromosomes.

Cigarette smoke contains some 5,000 organic compounds, including chemicals known to cause cancers. While the researchers did not expose cells to actual puffs of smoke, the cigarette smoke condensate they used was derived from burning real cigarettes and obtained from the R.J. Reynolds Tobacco Company. Containing mostly particulates, the extracted smoke was liquefied as part of a solvent mixture before it was exposed to the cells.

“Double-stranded breaks are considered the most mutagenic type of DNA damage because the broken ends can fuse to other chromosomes in the cell. Chromosome fusion is detrimental to normal chromosome segregation, which in turn leads to genetic imbalances,” explained Dr. Saunders, associate professor of biological sciences, University of Pittsburgh School of Arts and Sciences, and a researcher with the Oral Cancer Center of Discovery at the University of Pittsburgh Cancer Institute.

Before a cell undergoes division, its DNA is replicated and compressed into identical copies of each chromosome inside the cell nucleus. The chromosomes are then segregated during cell division, so that each daughter nucleus receives a complete copy of the genetic material. The stage when chromosomes are segregated and become separated is called anaphase. Normally, each set of chromosomes is pulled with equal force in opposite directions so that each daughter cell receives the same number of chromosomes.

But when the researchers exposed cells in culture to cigarette smoke, they found that the fused chromosomes were being pulled simultaneously from both directions much like a piece of taffy, forming so-called anaphase bridges between its two ends. Eventually, these chromosomes either tear apart, leaving two broken pieces, or if they don’t break apart, the abnormal, elongated chromosomes may persist after anaphase is completed. Either way, a major change in the structure of the chromosomes is the end result.

“Others have found the presence of anaphase bridges is correlated with chromosome instability in cancer cells. Because cigarette smoking is linked to oral, larynx, lung, bladder and esophageal cancers, our results showing that cigarette smoke can produce anaphase bridges and destabilize a cell’s chromosomes have added significance,” said Dr. Saunders.

“The failure of the cell to accurately repair the cigarette smoke condensate-induced double-stranded breaks probably leads to anaphase bridge formation and chromosomal instability,” added Li Z. Luo, Ph.D., a graduate student in the department of biological sciences, who will present the data.

According to their results, which also are detailed in an upcoming article in the journal Mutation Research, the development of anaphase bridges and chromosome instability is most likely due to reactive oxygen species that form as the cell is exposed to the various chemicals in smoke. Treating the smoke-exposed cells with different antioxidants, agents that block formation of reactive oxygen species, prevented most occurrences of anaphase bridge formation and significantly reduced genomic imbalances.

“Unfortunately, no amount of scientific evidence arguing against smoking will get everyone to stop or not begin to smoke in the first place. So, perhaps one long-term goal should be to develop cigarettes that somehow prevent what we’ve seen happen to the cells in our lab,” remarked Dr. Saunders.

In addition to Drs. Luo and Saunders, other authors of the abstract and paper are Kristen M. Werner, Ph.D., a former undergraduate student in the department of biological sciences; and Susanne M. Gollin, Ph.D., professor of human genetics at the University of Pittsburgh Graduate School of Public Health and co-investigator at the Oral Cancer Center of Discovery at the University of Pittsburgh Cancer Institute.

September, 2004|Archive|

Cigarette smoke combined with healthy saliva hastens cancer

  • 9/29/2004
  • Chicago, IL
  • no attribution
  • Journal of the American Dental Association

The Journal of the American Dental Association reported in its August edition that cigarette smoke combined with healthy saliva creates a mixture that can accelerate oropharyngeal cancer, according to researchers in the July 5 issue of British Journal of Cancer.

The report outlined that saliva contains antioxidants molecules that fight and neutralize harmful substances and help protect the body against cancer. Researchers examined its role in the development of oral cancer by recreating the effects of cigarette smoke on cancerous cells of the mouth. They exposed one-half of cancerous cell samples to cigarette smoke alone and the other one-half to a saliva and cigarette smoke mixture. They used cancerous cells in their study to assess quickly whether the saliva and smoke mixture would speed the cancer development.

Researchers found that cigarette smoke destroyed the antioxidants in the saliva and turned the saliva into a chemical mixture that could accelerate the development of mouth cancer. The longer the cancerous cells were exposed to the contaminated saliva, the more the cells were damaged.

“Most people will find it very shocking that the mixture of saliva and smoke is actually more lethal to cells in the mouth than cigarette smoke alone”, said study co-author Dr. Rafi Nagler. “Our study shows that once exposed to cigarette smoke, our normally healthy saliva not only loses its beneficial qualities but it turns traitor and actually aids in destroying the cells of the mouth and oral cavity. Cigarette smoke is not only damaging on its own, it can turn the body against itself.”

September, 2004|Archive|

Tumor Volume in Pharyngolaryngeal Squamous Cell Carcinoma: Comparison at CT, MR Imaging, and FDG PET and Validation with Surgical Specimen1

  • 9/29/2004
  • Jean-François Daisne, MD, Thierry Duprez et al
  • Radiology 2004;233:93-100

Purpose
To compare computed tomography (CT), magnetic resonance (MR) imaging, and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for delineation of gross tumor volume (GTV) in pharyngolaryngeal squamous cell carcinoma and to validate results with the macroscopic surgical specimen when available.

MATERIALS AND METHODS
Twenty-nine patients with stages II–IV squamous cell carcinoma treated with radiation therapy or chemotherapy and radiation therapy (n = 20) or with total laryngectomy (n = 9) were enrolled. Ten patients had oropharyngeal, 13 had laryngeal, and six had hypopharyngeal tumors. CT, MR imaging, and PET were performed with patients immobilized in a customized thermoplastic mask, and images were coregistered. GTVs obtained with the three modalities were compared quantitatively and qualitatively. If patients underwent total laryngectomy, images were validated with the surgical specimen after three-dimensional coregistration. The effect of each modality was estimated with linear mixed-effects models. Adjustments for multiple comparisons were made with the Bonferonni or Sidak method.

RESULTS
For oropharyngeal tumors and for laryngeal or hypopharyngeal tumors, no significant difference (P > .99) was observed between average GTVs delineated at CT (32.0 and 21.4 cm3, respectively) or MR imaging (27.9 and 21.4 cm3, respectively), whereas average GTVs at PET were smaller (20.3 [P .10] and 16.4 cm3 [P .01], respectively). GTVs from surgical specimens were significantly smaller (12.6 cm3, P .06). In nine patients for whom a surgical specimen was available, no modality adequately depicted superficial tumor extension; this was due to limitations in spatial resolution. In addition, false-positive results were seen for cartilage, extralaryngeal, and preepiglottic extensions.

CONCLUSION
Compared with GTVs at CT and MR imaging, GTVs at FDG PET were smaller. In nine patients for whom a surgical specimen was available, PET was found to be the most accurate modality. However, no modality managed to depict superficial tumor extension.

Jean-François Daisne, MD, Thierry Duprez, MD, Birgit Weynand, MD, Max Lonneux, MD, PhD, Marc Hamoir, MD, Hervé Reychler, MD, DDS and Vincent Grégoire, MD, PhD
From the Head and Neck Oncology Program, St-Luc University Hospital, Université Catholique de Louvain, 10 Ave Hippocrate, 1200 Brussels, Belgium

September, 2004|Archive|

Wine, beer and spirits and risk of oral and pharyngeal cancer: a case-control study from Italy and Switzerland

  • 9/28/2004
  • A Altieri, C Bosetti, et al
  • OralOncol, October 1, 2004; 40(9): 904-9

We examined the relation between consumption of different types of alcoholic beverages and the risk of oral and pharyngeal cancer, using data from a case-control study conducted in Italy and Switzerland between 1992 and 1997. This included a total of 749 cases of oral and pharyngeal cancer and 1,772 hospital controls, admitted for acute, non-neoplastic conditions, unrelated to alcohol and smoking consumption.

Significant trends in risk were found with increasing total alcohol intake, with multivariate odds ratios (OR) of 2.1 for drinkers of 3-4 drinks/day, as compared to abstainers or light drinkers (#10877;2 drinks/day), 5.0 for 5-7, 12.2 for 8-11 and 21.1 for #10878;12 drinks/day. Similar increased risks for subsequent levels of consumption were found for wine drinkers. After allowance for wine intake, the ORs for beer drinkers were 1.2 for 1-2 drinks/day, and 2.3 for #10878;3 drinks/day. Corresponding values for spirit drinkers were 1.0 and 1.9. Patterns of risk for wine drinkers were similar for wine only drinkers and drinkers of wine, plus beer and spirits. Our study indicates that in populations with frequent wine consumption, wine per se can strongly increase the risk of cancer of the oral cavity and pharynx, and confirms that the most prevalent alcoholic beverage in each population tends to be the one with the highest risk.

September, 2004|Archive|

Smokeless tobacco use is associated with a substantial risk of oral cancers in India

  • 9/28/2004
  • Gail Topping & JA Critchley, B Unal.
  • Evidence-Based Dentistry, 2004, Volume 5, Number 3, Pages 79-79

Data sources
Medline, Embase, CINAHL and Dissertation Abstracts were searched, supplemented by screening reference lists, smoking-related websites, and contacting experts.

Study selection
Analytical observational studies of use of smokeless tobacco (ST; cohorts, case-control, cross-sectional studies) with a sample size of 500 were included if they reported on one or more of the following outcomes: mortality from any cause, oral and pharyngeal cancers, other cancers, cardiovascular diseases, dental diseases, pregnancy outcomes or surgical outcomes.

Data extraction and synthesis
Data extraction covered control of confounding, selection of cases and controls, sample size, clear definitions and measurements of the health outcome, and ST use. Selection, extraction and quality assessments were carried out by one or two independent reviewers.

Results
Many of the studies lacked sufficient power to estimate precise risks, mainly because of the small number of ST users. Studies were often not designed to investigate ST use, and many also had major methodological limitations including poor control for cigarette smoking and imprecise measurements of exposure. Studies in India showed a substantial risk of oral or oropharyngeal cancers associated with chewing betel quid and tobacco. Studies from other regions and of other cancer types were not consistent. Few studies have adequately considered the non-cancer health effects of ST use.

Conclusions
Chewing betel quid and tobacco is associated with a substantial risk of oral cancers in India. Most recent studies from the US and Scandinavia are not statistically significant, but moderate positive associations cannot be ruled out due to lack of power. Further rigorous studies with adequate sample sizes are required, especially for cardiovascular disease.

Dr J Critchley, Department of Public Health, University of Liverpool, Liverpool

Gail Topping, Dental Health Services Research Unit, University of Dundee, Dundee, Scotland, UK

Reference:
JA Critchley, B Unal. Health effects associated with smokeless tobacco: a systematic review. Thorax 2003; 58:435-443

September, 2004|Archive|

Beating Tongue Cancer

  • 9/27/2004
  • TAMPA, FL
  • Ivanhoe Broadcast News
  • HealthCentral.com

Combining radiation and chemotherapy to kill cancer cells is often very difficult on patients because of the side effects, but new research shows the results may be worth it.

Days like this with her family make it all worthwhile for Ruth Toseland. Three years ago, she was diagnosed with tongue cancer. A portion of her tongue was removed, but the cancer came back. After two more surgeries, she opted for an extreme treatment — radiation combined with chemotherapy.

Oncologist Julie A. Kish, M.D., of Moffitt Cancer Center in Tampa, Fla., was involved in a national study that may change the treatment of choice for patients at high risk for recurrence. “At two years, the recurrence rate was lower in patients that had the combined treatment as opposed to radiation alone,” she tells Ivanhoe.

But the treatment is very hard on the patient. Researchers say four of the 228 patients in the study died as a result of the combined therapy. Still, Dr. Kish says, for some, the tough approach is worth it. “If you can prolong the time until the cancer comes back, which potentially, at some point in time, it may not come back, which we never say because we can’t predict that, it’s worth going through it.”

Ruth finished her treatment two and half years ago. So far, the cancer has not returned. Her husband, Michael, says, “We’ve got a lot to be thankful for. It was touch and go for a long time.” Ruth’s case was unusual in the sense that she had no risk factors for head and neck cancer. This type of cancer usually happens to men over age 50 that smoke and/or drink. Dr. Kish says the longer the patient goes without recurrence, the less likely it is that the cancer will come back. The first two years are the most risky.

September, 2004|Archive|

Smokeless Tobacco and Cardiovascular Risk

  • 9/27/2004
  • Ritesh Gupta, MD, MPH; Hitinder Gurm, MD; John R. Bartholomew, MD
  • Archives of Internal Medicine, 2004;164:1845-1849

This article discusses the evolution of smokeless tobacco in the United States and interprets the available data on cardiovascular risk factors and cardiovascular mortality associated with its use. There has been a resurgence of smokeless tobacco use since 1970. Smokeless tobacco consistently produces levels of nicotine higher than those seen with smoking and causes similar sympathetic neural stimulation and acute cardiovascular effects. However, there is conflicting evidence from prospective and case-control studies about cardiovascular mortality or myocardial infarction caused by smokeless tobacco use. Smokeless tobacco use is also associated with oral cancers and high-risk behavior in adolescents. Although the evidence is not conclusive, the adverse cardiovascular effects of smokeless tobacco use are less than those caused by smoking but are more than those found in nonusers. It is advisable to counsel all current users of smokeless tobacco to quit. Behavioral counseling, sustained-release bupropion hydrochloride therapy, and nicotine replacement therapy may be safe therapeutic modalities for treatment of smokeless tobacco use.

From the Departments of Internal Medicine (Dr Gupta) and Cardiovascular Medicine (Drs Gurm and Bartholomew) and the Section of Vascular Medicine (Dr Bartholomew), The Cleveland Clinic Foundation, Cleveland, Ohio.

September, 2004|Archive|

History of smoking significantly reduces survival in head and neck cancer patients

  • 9/30/2004
  • Houston, TX
  • Journal of Clinical Oncology

A new study shows that a history of smoking affects survival in patients with cancer of the head and neck. Patients who had smoked fewer than 100 cigarettes in their lifetime were three times more likely to have better overall survival, disease-specific survival, and recurrence-free survival compared with patients who had a current or previous history of regular smoking.

There are approximately 38,000 new cases of head and neck cancer cases in the U.S. each year, the vast majority of which occur in smokers.
The study, to be published October 1 in the Journal of Clinical Oncology, is the first to compare survival in pairs of head and neck cancer patients who differ in smoking status but are matched for other factors. The study provides a more accurate assessment of the link between smoking status and survival by limiting other factors that could affect observed disease outcome. “These findings support previous studies indicating that molecular differences exist between the tumors of smokers and non-smokers and may actually reflect two separate types of head and neck cancer,” said Erich M. Sturgis, MD, MPH, in the Department of Head and Neck Surgery at the University of Texas M. D. Anderson Cancer Center and senior author of the study. “Our study suggests that the changes that occur in smokers may lead to a more aggressive form of the disease that results in poorer survival.”

Although the relative risk of developing head and neck cancer is three to 12 times higher for smokers than for non-smokers, the impact of smoking on disease outcome is unclear. Past studies have had difficulty measuring the effect of smoking status on survival because non-smokers who develop the disease generally differ demographically than patients with a previous or current history of smoking.

In the current study, researchers used a database of more than 500 patients with newly diagnosed, previously untreated head and neck cancer, including 83 non-smokers. Each non-smoker was paired with a smoker with similar age, sex, tumor location, disease stage, lymph node status, and treatment history. Applying these matching criteria yielded 50 pairs of head and neck cancer patients for further study. Several other factors, including alcohol use, additional medical conditions, and cancer-associated symptoms such as weight loss, earache, and difficulty swallowing were not included as matching criteria, but were statistically evaluated to assess their impact on survival.
Researchers found that the risk of death, death due to the disease, and disease recurrence was more than three times higher for people with a history of smoking.

Researchers underscored the importance of aggressively promoting tobacco cessation and moderation of alcohol use, as well as managing disease symptoms and other medical conditions in order to improve the quality of life and survival of people living with head and neck cancer.

“Matched-Pair Analysis of Survival of Never-Smokers and Ever-Smokers with Squamous Cell Carcinoma of the Head and Neck.” Kristen B. Pytynia et al, The University of Texas M. D. Anderson Cancer Center. The Journal of Clinical Oncology is the semi-monthly peer-reviewed journal of the American Society of Clinical Oncology (ASCO), the world’s leading professional society representing physicians who treat people with cancer.

September, 2004|Archive|