Head and neck squamous cell carcinoma: better to be young.

Most head and neck squamous cell carcinoma patients are elderly, with few younger than 40 years. Controversy exists in the literature regarding outcomes for younger patients. The goal of this research project was to compare baseline features and outcomes for young patients (/=65 years). To investigate the relationship between age and important presenting features and outcomes, 1160 recently diagnosed patients first treated at Washington University between 1980 and 1991 were identified from an existing database. Full 5-year survival information was available for 1030 patients (89%). Overall, the 5-year survival rate was 46% (478/1030); young patients (65%, 26/40) had a significantly better survival rate than middle-aged (52%, 292/566) or old patients (38%, 160/424) (chi(2) = 24.5; P = 0. 001). Survival was also related to smoking, comorbidity, primary site, TNM stage, and nodal disease. Age remained a significant factor even after we controlled for these other factors. Young patients developed fewer recurrent and new primary tumors. We conclude that young patients have a much better overall prognosis than older patients. The reasons for this difference are unclear, but it appears that the impact of age goes beyond an actuarial effect.

Symptoms as an index of biologic behavior in head and neck cancer.

The TNM staging system for head and neck cancer is based on the morphologic description of the tumor and disregards the clinical condition of the patient. Cancer symptoms were evaluated as a biologic index of disease to improve survival estimates. The medical records of 1010 patients receiving initial cancer treatment between 1980 and 1991 were retrospectively reviewed. The mean survival duration was 62 months for the entire population. By use of SAS statistical software (SAS Institute, Cary, NC), 48 symptom variables were screened by univariate analysis, and 23 of these variables were selected for entry into a Cox proportional hazards model on the basis of survival duration. Dysphagia, otalgia, neck lump, and weight loss were identified as independent predictors of survival duration (P < 0.01). A composite symptom-severity staging system was created on the basis of the 4 symptoms. Mean survival duration (95% CI) by symptom-severity stage was as follows: none, 74 months (70 to 79 months); mild, 56 months (51 to 61 months); moderate, 40 months (33 to 47 months); and severe, 31 months (22 to 41 months) (chi 2 = 30.8, P = 0.0001). Survival duration by TNM stage was as follows: I, 89 months (82 to 95 months); II, 71 months (65 to 78 months); III, 53 months (47 to 59 months); and IV, 42 months (37 to 47 months) (chi 2 = 56.2, P = 0.0001). When symptom-severity stage was entered in a proportional-hazards model along with TNM stage, comorbidity, age, and alcohol use, all 5 variables were independently predictive of survival duration (risk ratio: symptom severity 1.28, TNM 1.33, comorbidity 1.80, age 1.47, alcohol use 1.09). Appropriately defined symptom variables contain important prognostic information, which is independent of the TNM system. Therefore symptoms provide an index of biologic behavior in head and neck cancer.

Clinical-severity staging system for oral cavity cancer: five-year survival rates.

The objective of this research is to improve the classification and survival estimates for patients with oral cavity cancer by combining cancer symptom severity and comorbidity with the current TNM staging system. The study design is a retrospective medical record review that uses explicit coding criteria. The medical records of 277 patients receiving initial treatment at the Washington University Medical Center between 1980 and 1989 were reviewed. Multivariate analysis identified patient factors that significantly affected 5-year survival. These patient factors, symptom severity and comorbidity, were combined with TNM to create a composite clinical-severity staging system. The overall 5-year survival rate was 46% (128/277). Survival rates by TNM stage were as follows: stage I, 72% (36/50); II, 54% (45/84); III, 37% (24/65); and IV, 29% (23/78) (chi2 = 25.27, P = 0.001). When patients were grouped according to the clinical-severity staging system, survival rates were as follows: stage I, 77% (33/43); II, 56% (45/80); III, 42% (43/103); and IV, 14% (7/51) (chi2 = 40.62, P = 0.001). Survival estimates can be improved by adding carefully studied and suitably defined patient variables to the TNM system. The current TNM staging system for oral cavity cancer is based solely on the morphologic description of the tumor and disregards the clinical condition of the patient. Patient factors, such as cancer symptom severity and comorbidity, have a significant impact on survival. Continued exclusion of patient factors leads to imprecision in prognostic estimates and hinders interpretation of clinical studies.

Clinical correlations with allelotype in supraglottic squamous cancer.

Frequent allelic loss at a genetically polymorphic locus in tumors is an established marker for the presence of a tumor suppressor gene in the neighboring chromosomal region. This technique can be used to identify novel tumor suppressor genes and to monitor their status before the cloning of the gene itself. We have used the polymerase chain reaction and microsatellite loci on all 39 nonacrocentric autosomal chromosomal arms to identify sites of frequent allelic loss in squamous cell carcinomas of the supraglottic larynx. Our allelotype identified seven chromosomal arms (3p, 5q, 8p, 9p, 9q, 13q, and 17p) likely to contain tumor suppressor genes frequently inactivated during squamous tumorigenesis in the larynx. We tested for associations between allelic losses on these chromosomal arms and the clinical and histopathologic features of these tumors. There were no correlations with either T or N classifications. Allelic loss on chromosomal arm 13q is significantly associated with a number of histopathologic features characteristic of poorly differentiated or histologically aggressive tumors. Allelic loss on this arm also exhibits statistical trends toward association with early tumor recurrence and poor survival. The association with survival was substantiated by a multivariate Cox proportional hazards model.

Clinical-severity staging system for oropharyngeal cancer: five-year survival rates.

OBJECTIVE: To improve the classification and survival estimates for patients with oropharyngeal cancer by combining cancer symptom severity and comorbidity with the current TNM cancer staging system. DESIGN: Retrospective medical record review using explicit coding criteria. SETTING: University medical center. PATIENTS AND METHODS: Two hundred ninety-six patients receiving initial treatment from January 1, 1980, to December 31, 1989. Multivariate analysis identified patient factors that had a significant impact on 5-year survival. These patient factors, symptom severity and comorbidity, were combined with cancer stage to create a composite clinical-severity staging system. MAIN OUTCOME MEASURE: Five-year survival. RESULTS: The overall 5-year survival rate was 38% (111/ 296). Survival by TNM cancer stage was 67% (18/27) for stage I, 46% (24/52) for stage II, 31% (26/85) for stage III, and 32% (43/132) for stage IV (chi2=10.84; P=.001). When patients were grouped according to the clinical-severity staging system, survival rates were 70% (16 of 23) for stage A, 47% (71 of 152) for stage B, 27% (18 of 67) for stage C, and 11% (6 of 54) for stage D (chi2=34.49; P=.001). CONCLUSIONS: Survival estimates can be improved by adding carefully studied and suitably defined patient variables to the TNM cancer stage. The current TNM cancer staging system for oropharyngeal cancer is based solely on the morphologic description of the tumor and disregards the clinical condition of the patient. Cancer symptom severity and comorbidity have a significant impact on survival. Continued exclusion of patient factors leads to imprecision in prognostic estimates and hinders interpretation of clinical studies.

Chromosome 8 allelic loss and the outcome of patients with squamous cell carcinoma of the supraglottic larynx.

BACKGROUND: Loss of genetic heterogeneity (allelic loss or loss of heterozygosity) on chromosome arm 8p is frequent in squamous cell carcinomas of the head and neck and has been associated with poor prognosis. We have previously demonstrated that there are three minimal regions of allelic loss on this chromosome arm. The location of each region is marked by a microsatellite locus: D8S264 (8p23), D8S552 (8p23-p22), and D8S133 (8p21). These findings imply the existence of at least three putative tumor suppressor genes on this chromosome arm that may become inactivated during the progression of squamous cell carcinoma. PURPOSE: We used allelic loss data from these three loci to determine if inactivation of these putative suppressors is associated with poor prognosis for patients with squamous cell carcinoma of the supraglottic larynx. We also used multivariate statistics to compare the prognostic power of allelic loss at these genetic markers with that of demographic, clinical, and histopathologic parameters. METHODS: We examined the D8S264, D8S552, and D8S133 microsatellites in tumors from a retrospective population of 59 patients. All patients had histologically confirmed squamous cell carcinoma of the supraglottic larynx and had been treated surgically. DNA was extracted from matched sets of normal and microdissected tumor tissue and used for polymerase chain reaction amplification of the microsatellite markers. Reaction products were separated by denaturing gel electrophoresis and visualized by autoradiography. Patient data were obtained from the original pathology report and from the tumor registry of the Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO. Histopathologic data were obtained by reviewing the portion of the resection specimen used for DNA extraction. Parameters whose association with reduced disease-free interval and reduced disease-specific survival was statistically significant were identified by use of the Kaplan-Meier method and the logrank statistic. Multivariate Cox proportional hazards models were used to identify independent predictors of poor prognosis. All statistical tests were two-sided. RESULTS: In this patient population, allelic loss at the D8S264 locus was associated with both shorter disease-free interval (logrank P = .028) and reduced disease-specific survival (logrank P = .004). Allelic loss at the next most centromeric locus, D8S552, had a statistically significant association with only reduced disease-specific survival (logrank P = .034), whereas allelic loss at the most centromeric region, D8S133, showed no statistically significant association with reductions in either interval. Multivariate Cox models suggested that D8S264 was the only 8p marker of the three microsatellites with a statistically significant and independent association with shortened disease-free interval (relative risk [RR] = 3.38; P = .0107) and reduced disease-specific survival (RR = 3.41; P = .0105). CONCLUSIONS: Allelic loss in the p23 region of chromosome 8 appears to be a statistically significant, independent predictor of poor prognosis in patients with supraglottic squamous cell carcinoma.