7/24/2005 Raleigh, NC staff Cancer Wire (July 2005 Edition) John, age eight, was diagnosed with an Anaplastic Astrocytoma (AA) which is an aggressive and often fatal brain tumor. He underwent brain surgery followed by high-dose chemotherapy and radiation therapy (equivalent to about 50,000 dental x-rays). These treatments are highly toxic to the developing brain of a child and, if he were to survive, his IQ and cognitive abilities would be seriously compromised. The family moved to a different state and took John to the local children’s hospital for follow-up care. There, the doctors reviewed John’s pathology slides. They discovered that John’s tumor was not an AA, but was benign. This diagnosis was subsequently confirmed by two other hospitals. John never needed chemotherapy or radiation therapy. Today, John’s IQ decreases at a rate of about 6 points a year as he suffers from the side-effects of a treatment he never needed. Pathology is the medical specialty that deals with the examination of tissues and cells under the microscope in order to arrive at a diagnosis. When it comes to cancer, a pathological diagnosis is the gold standard that indicates the presence or absence of cancer, the type of cancer, and its classification. Because therapeutic decisions are based on the presumed reliability of the pathology diagnosis, a misdiagnosis can result in unnecessary, harmful and aggressive therapy (like John’s story) or inadequate treatment. Unfortunately, medical studies over the last two decades have demonstrated that this gold standard is not consistently reliable. In fact, [...]

7/20/2005 South Bend, IN Patty Levine South Bend Tribune (www.southbendtribune.com) At your next periodic dental checkup and cleaning, your dentist might take a few extra minutes to examine your tongue, gums, the roof and floor of your mouth. This thorough mouth exam probes for oral cancer, a disease which will strike 30, 000 Americans this year and kill 8,000. But within two years, you may be able to go for your regular dental visit, spit in a cup and, before the appointment is over, find out from an analysis of your saliva whether you're at risk for oral cancer. In a small study reported last year, at the American Association for Cancer Research in Anaheim, Calif., researchers from the UCLA School of Dentistry found that genetic "biomarkers" isolated in saliva predicted oral cancer in about nine out of 10 cases. According to this team of scientists, out of about 3,000 distinct bits of genetic material called messenger RNA in saliva, the appearance of four particular "biomarkers" may signal the presence of cancer of the mouth, tongue, larynx or pharynx -- even before any symptoms appear. Although it is not yet clear whether these four RNA particles are detectable because their corresponding genes are activated, or whether their presence indicates the body's inflammatory response to the cancer, the use of saliva for predicting cancer is significant. And in a study reported this past April from Johns Hopkins Medical Institutions, scientists found that an increase of another type of genetic material found [...]

7/19/2005 Isabelle Bairati et al. Journal of Clinical Oncology, 10.1200/JCO.2005.05.514 This Article Purpose: Many cancer patients take antioxidant vitamin supplements with the hope of improving the outcome of conventional therapies and of reducing the adverse effects of these treatments. A randomized trial was conducted to determine whether supplementation with antioxidant vitamins could reduce the occurrence and severity of acute adverse effects of radiation therapy and improve quality of life without compromising treatment efficacy. Patients and Methods: We conducted a randomized, double-blind, placebo-controlled trial among 540 head and neck cancer patients treated with radiation therapy. Patients were randomly assigned into two arms. The supplementation with -tocopherol (400 IU/d) and -carotene (30 mg/d) or placebos was administered during radiation therapy and for 3 years thereafter. During the course of the trial, supplementation with -carotene was discontinued because of ethical concerns. Results: Patients randomly assigned in the supplement arm tended to have less severe acute adverse effects during radiation therapy (odds ratio [OR], 0.72; 95% CI, 0.52 to 1.02). The reduction was statistically significant when the supplementation combined -tocopherol and -carotene for adverse effects to the larynx (OR, 0.38; 95% CI, 0.21 to 0.71) and overall at any site (OR, 0.38; 95% CI, 0.20 to 0.74). Quality of life was not improved by the supplementation. The rate of local recurrence of the head and neck tumor tended to be higher in the supplement arm of the trial (hazard ratio, 1.37; 95% CI, 0.93 to 2.02). Conclusion: Supplementation with high doses of -tocopherol and [...]

7/19/2005 Ann Arbor, MI press release EurekAlert (www.eurekalert.org) University of Michigan researchers have figured out one more component in cancer cells' aggressive growth---and hope that knowledge can help kill the cells. In the July issue of Cancer Cell, the scientists explain how cancer tumor cells attach themselves to a protein on the surface of cells lining blood vessel walls. When this attachment happens, it tells the cancer cell to grow and develop blood vessels, which feed the cell. Cun-Yu Wang, senior author on the paper, said this discovery could help in the fight against cancer. "The blood supply is key for tumor growth and tumor development," said Wang, the Richard H. Kingery Endowed Collegiate Professor at the U-M School of Dentistry. "If you cut off the blood supply, you stop cancer development." Wang collaborated with researchers Qinghua Zeng, Shenglin Li, Douglas B. Chepeha, Jong Li, Honglai Zhang, Peter J. Polverini, Jacques Nor and Jan Kitajewski on the paper. Scientists have heavily studied cancer cells' secretion of proteins to form blood vessels. But Wang said when researchers tried to turn off that process, some tumors responded and some did not, which left him curious about how to develop a better treatment. Rather than simply looking for a better way to interrupt the protein secretion, Wang and colleagues looked for other ways that tumor cells might develop their blood supply, a process called angiogenesis. Wang's team has studied hepatocyte growth factor, known as HGF, to better understand its function in the formation [...]

7/19/2005 Ann Arbor, MI press release EurekAlert (www.eurekalert.org) A compound derived from cottonseed could help improve the effectiveness of chemotherapy at treating head and neck cancer, researchers at the University of Michigan Comprehensive Cancer Center have found. The findings, which appear in the July issue of the journal Molecular Cancer Therapeutics, could lead to a treatment that provides an effective option to surgically removing the cancer, helping patients preserve vital organs involved in speech and swallowing. While new treatments in head and neck cancer have allowed some patients to undergo chemotherapy and radiation therapy instead of surgery, this form of cancer is often resistant to chemotherapy. When the cancer does not respond to these powerful drugs, patients must resort to surgery. "Patients really benefit long-term by avoiding surgery because the side effects of surgery for head and neck cancer can be particularly difficult for patients. It affects how you talk, how you swallow and how you breathe," says study author Carol Bradford, M.D., professor of otolaryngology at the U-M Medical School and co-director of the Head and Neck Oncology Program at the U-M Comprehensive Cancer Center. The compound, (-)-gossypol, works to regulate a protein called Bcl-xL that's overexpressed in cancer cells and makes these cells survive when they shouldn't. Shaomeng Wang, Ph.D., co-director of the Molecular Therapeutics Program at the U-M Comprehensive Cancer Center, discovered (-)-gossypol, a compound derived from a component of Chinese medicine. Gossypol comes from cottonseed and was once used in China as a male contraceptive. More [...]

7/19/2005 Chicago, IL Marina Boruk, MD et al. Arch Otolaryngol Head Neck Surg. 2005;131:605-609 Objective: To determine if age alone is a prognostic indicator of surgical outcomes for major head and neck procedures. Design: Retrospective cohort study over a 4-year period. Setting: Academic referral center, institutional practice, hospitalized care. Patients: Included in this study were patients who had undergone ablative, reconstructive, and other major surgical procedures of the head and neck, including neck dissection, laryngectomy, maxillectomy, thyroidectomy with lymphadenectomy, and composite resection of the oral cavity with reconstruction, for both malignant and benign disease. Main Outcome Measures: Patient data and intraoperative and postoperative course factors were recorded. Comorbidity was graded using an Adult Comorbidity Evaluation 27 test, Charlson Comorbidity Index, and American Society of Anesthesiology score. Postoperative complications were dichotomized, and multiple logistic regression was used for data analysis. Results: Medical chart review identified 157 cases. Analysis of data revealed that time under general anesthesia was the only factor consistently related to complications (P<.006), and it was the only factor consistently related to length of stay (P<.001). Analysis of major complications (6% incidence) as an outcome using univariate analysis resulted in a strong positive correlation with both comorbidity indexes: Adult Comorbidity Evaluation 27 (P = .002) and Charlson Comorbidity Index (P = .005). Multiple logistic regression showed no significant relationship between age 70 years or older (20% of patients) and either complications or hospital length of stay. Conclusions: Patient’s age alone is not a prognostic indicator of surgical outcome for [...]

7/19/2005 Chicago, IL Frank R. Miller, MD et al. Arch Otolaryngol Head Neck Surg. 2005;131:626-629 Objective: To assess the role of positron emission tomography (PET) in the management of unknown primary carcinoma of the head and neck region. Design and Setting: Prospective case series at an academic medical center. Patients: Twenty-six patients with an open excisional biopsy or a fine-needle aspiration biopsy finding that confirmed squamous cell carcinoma of the cervical lymph nodes and no visible primary tumor (as determined by results of a comprehensive physical examination and computed tomography and/or magnetic resonance imaging) underwent PET. The standard evaluation consisted of a comprehensive head and neck examination that included fiberoptic laryngoscopy/nasopharyngoscopy, computed tomography and/or magnetic resonance imaging, and PET followed by panendoscopy with selected biopsies and tonsillectomy. Main Outcome Measures: Sensitivity, specificity, and positive and negative predictive values of PET to detect an occult primary tumor. Results: The PET detected 8 occult primary tumors in 26 patients (detection rate, 30.8%). Four occult primary tumors (2 at the base of the tongue and 2 in the tonsil) were detected during routine panendoscopy with negative PET findings. The sensitivity of PET was 66.0%, with a specificity of 92.9%. The positive predictive value was 88.8%, and the negative predictive value was 76.5%. Conclusions: Positron emission tomography can be a valuable tool to identify a subset of patients with an occult primary tumor in the head and neck region. In addition, it can be used to screen for primary tumors below the clavicle. Early [...]

7/19/2005 Bethesda, MD Lisa M. McShane, Douglas G. Altman, Willi Sauerbrei Journal of the National Cancer Institute, Vol. 97, No. 14, 1023-1025, July 20, 2005 The number of cancer prognostic markers that have been validated as clinically useful is pitifully small, despite decades of effort and money invested in marker research (1–3). For nearly all markers, the product has been a collection of studies that are difficult to interpret because of inconsistencies in conclusions or a lack of comparability. Small, underpowered studies; poor study design; varying and sometimes inappropriate statistical analyses; and differences in assay methods or endpoint definitions are but a few of the explanations that have been offered for this disappointing state of affairs (4–11). Researchers attempting to conduct meta-analyses of prognostic marker studies encounter many difficulties (12–14). In this issue of the Journal, a meta-analysis by Kyzas et al. (15) of the tumor suppressor protein TP53 as a prognostic factor in head and neck cancer provides compelling empirical evidence that selective reporting biases are a major impediment to conducting meaningful meta-analyses of prognostic marker studies. These biases have serious implications, not only for meta-analyses but also for interpretation of the cancer prognostic literature as a whole. Kyzas et al. demonstrate bias in the estimated association between TP53 status and mortality relating to a number of factors. The prognostic importance of TP53 decreased as the pool of included studies increased from published and indexed studies to any published studies, and then to the full set of all published [...]

7/19/2005 Bethesda, MD Elana Hayasaka Journal of the National Cancer Institute, Vol. 97, No. 14, 1019, July 20, 2005 Selective reporting biases may taint many published studies of so-called prognostic factors—biologic or genetic markers that may predict how a patient may fare during or after treatment, according to a new study in the July 20 issue of the Journal of the National Cancer Institute. In recent years, researchers have raced to discover and publish papers on prognostic factors for cancer and other diseases. For example, at least 116 published studies alone have focused on a single tumor suppressor protein (TP53) that may predict the outcome of a patient with head and neck cancer. As researchers attempt to make sense of the growing mountains of information, some are beginning to question the validity and possible biases in many of the studies. To examine the question of selective reporting bias, Panayiotis A. Kyzas and colleagues from the University of Ioannina in Greece analyzed information from studies that investigated the association between TP53 and mortality or survival rates. They collected three levels of information about the studies. The first level included studies that were indexed in the scientific databases MEDLINE and EMBASE using the key words "mortality" or "survival." The other two levels of collected information include published studies not indexed under "mortality" or "survival", and unpublished data retrieved from researchers. The authors found that the association between TP53 status and head and neck cancer mortality weakened as they expanded their analyses from [...]

7/19/2005 Bethesda, MD Panayiotis A. Kyzas, Konstantinos T. Loizou, John P. A. Ioannidis Journal of the National Cancer Institute, Vol. 97, No. 14, 1043-1055, July 20, 2005 Background: Nonreported and selectively reported information and the use of different definitions may introduce biases in the literature of prognostic factors. We probed these biases in a meta-analysis of a prognostic factor for head and neck squamous cell cancer (HNSCC) mortality that has drawn wide attention—the status of the tumor suppressor protein TP53. Methods: We compared results of meta-analyses that included published data plus unpublished data retrieved from investigators; published data; and only published data indexed with "survival" or "mortality" in MEDLINE/EMBASE, with or without standardized definitions. We also evaluated whether previously published meta-analyses on mortality predictors for various malignancies addressed issues of retrieval and standardized information. All statistical tests were two-sided. Results: For the 18 studies with 1364 patients that included published and indexed data, we obtained a highly statistically significant association between TP53 status and mortality. When we used the definitions preferred by each publication, the association was stronger (risk ratio [RR] = 1.38, 95% confidence interval [CI] = 1.13 to 1.67; P = .001) than when we standardized definitions (RR = 1.27, 95% CI = 1.06 to 1.53; P = .011). The addition of 13 studies with 1028 subjects that included published but not indexed data reduced the observed association (RR = 1.23, 95% CI = 1.03 to 1.47; P = .02). Finally, when we obtained data from investigators (11 [...]