Stimson P. Schantz

Prevention of Second Primary Tumors with Isotretinoin in Squamous-Cell Carcinoma of the Head and Neck

BACKGROUND Patients with head-and-neck cancers who are free of disease after local therapy remain at high risk for both recurrent and second primary tumors. Retinoids have proved efficacious in the treatment of premalignant oral lesions and are promising agents for the prevention of epithelial carcinogenesis. METHODS We prospectively studied 103 patients who were disease-free after primary treatment for squamous-cell cancers of the larynx, pharynx, or oral cavity. After completion of surgery or radiotherapy (or both), these patients were randomly assigned to receive either isotretinoin (13-cis-retinoic acid) (50 to 100 mg per square meter of body-surface area per day) or placebo, to be taken daily for 12 months. RESULTS There were no significant differences between the two groups in the number of local, regional, or distant recurrences of the primary cancers. However, the isotretinoin group had significantly fewer second primary tumors. After a median follow-up of 32 months, only 2 patients (4 percent) in the isotretinoin group had second primary tumors, as compared with 12 (24 percent) in the placebo group (P = 0.005). Multiple second primary tumors occurred in four patients, all of whom were in the placebo group. Of the 14 second cancers, 13 (93 percent) occurred in the head and neck, esophagus, or lung. CONCLUSIONS Daily treatment with high doses of isotretinoin is effective in preventing second primary tumors in patients who have been treated for squamous-cell carcinoma of the head and neck, although it does not prevent recurrences of the original tumor.

Genetic differences detected by comparative genomic hybridization in head and neck squamous cell carcinomas from different tumor sites: construction of oncogenetic trees for tumor progression

For a better understanding of genetic alterations in head and neck squamous cell carcinoma (HNSCC), we applied comparative genomic hybridization (CGH) in the analysis of 75 HNSCCs, comprised of 18 pharyngeal squamous cell carcinomas (PSCCs), 23 laryngeal squamous cell carcinomas (LSCCs), and 34 oral squamous cell carcinomas (OSCCs). The three subgroups of HNSCC showed significant differences in genetic alteration patterns. Overall, PSCC and LSCC had more copy number aberrations (CNAs) per tumor than did OSCC. Apparent differing patterns of high‐level amplification were also observed. The smallest recurrent chromosomal regions of high‐level amplification (≥15% of cases) were 7q22, 8q24.1, and 11q12–13 in PSCC and 3q26.1–29 in OSCC. According to single frequency and combined frequencies of CNAs, we concluded that the most important chromosomal events for progression of head and neck cancer were +3q, +5p, +8q, and −3p for all subgroups of HNSCC; additionally, +7q, +17q, −9p, and −13q for PSCC; +7p, +9q, +11q12–13, +14q, and +17q for LSCC; and +1p and +11q12–13 for OSCC. To identify further important genetic alterations and the relationships among the alterations, we constructed oncogenetic tree models for tumor progression of HNSCC from CGH data using branching and distance‐based tree models. The tree models predicted that: (1) +3q21–29 was the most important early chromosomal event, and −3p, which occurred after +3q21–29, was also an important chromosomal event for all subsites of HNSCC; (2) +8q is the second most important early chromosomal event; (3) there may be at least three subgroups of HNSCC: one characterized by −3p, −9p, +7p, and −13q; another by +5p, +9qter, and +17p; and the other by +8q and +18p. These results suggest that different chromosomal aberrations may play a role in the initiation and/or progression of different subgroups of HNSCC.

Second-harmonic tomography of tissues

A novel noninvasive second-harmonic-generation tomographic method of mapping the structure of animal tissues by use of 100-fs laser pulses at 625nm is described. Subsurface structures were measured with this approach, which is potentially a symmetry-sensitive tool for optical histological reconstruction.

Squamous cell carcinoma of the tongue in young patients: A matched-pair analysis

Tongue cancer is seen with increasing frequency in young individuals. There is controversy concerning the clinical course and outcome for oral tongue cancer in young patients.

Thyroid cancer incidence and survival in the national cancer institute surveillance, epidemiology, and end results race/ethnicity groups.

BACKGROUND Thyroid cancer incidence has continuously increased for decades and the causes of this increase are still controversial. The objective of this study was to examine if the increased trend is different among the different National Cancer Institute (NCI) Race/Ethnicity Groups (REGs) within the NCI surveillance epidemiology and end results database for the United States. METHODS Using recent 13-year surveillance epidemiology and end results data, we described the specific incidence trend of thyroid cancer for the REGs by tumor size, tested the statistical significance of the trend of incidence, and estimated the annual percentage change (APC) and 95% confidence interval. In addition, we compared the difference of 5-year survival rate among the REGs. RESULTS Papillary thyroid cancer incidence significantly increased over 13 years from 1992 to 2004 among the five major REGs. The estimated APC was 5.6% (95% confidence interval = 5.1%-6.1%, p < 0.01) for the non-Hispanic whites group, 4.3% (3.0-5.5, p < 0.01) for the Blacks group, 2.8% (1.5-4.2, p < 0.01) for the Hispanic whites group, 1.5% (0.5-2.5, p < 0.01) for the Asians group, and 1.1% (-2.2-4.6, p = 0.477) for the American Indians/Alaska Natives group, respectively. The APCs among the REGs were significantly different (Z = 7.89, p < 0.001). The upward incidence trend could be seen in all small or large tumors as well as in women or in men. The proportion of local staged thyroid cancer increased by 24% in the Blacks group, 14.4% in the Hispanic whites group, 14.3% in the non-Hispanic whites group, and only 4.0% in the Asians group between two periods of 1992-1996 and 2000-2004. Five-year survival rates of patients with papillary tumor were about 95%, but that of anaplastic tumor ranged from 5.6% to 11.4% among REGs. CONCLUSION The time trend of incidence of thyroid cancer is different among the different NCI REGs. Differences in diagnostic scrutiny may explain the differences in the REG-related trend, but this cannot easily explain the relatively small degree of increase in the trend in the Asian and the Indians/Alaska Natives groups nor can it explain the increase in the trend of large tumors that are likely to be discovered by self-palpation by patients.

Molecular support for field cancerization in the head and neck

Two competing concepts, field cancerization and micrometastatic lesions, have been postulated to account for the high frequency of second primary tumors and multicentric dysplasia in patients with head and neck carcinoma.

Planned Neck Dissection after Concomitant Radiochemotherapy for Advanced Head and Neck Cancer

Objectives/Hypothesis: Since 1998, at our academic, multidisciplinary head and neck cancer treatment center, it has been our policy to treat appropriate patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) with concomitant radiochemotherapy followed within 6 weeks by planned neck dissection(s). Our objective was to investigate the oncologic efficacy of planned neck dissection, to date, in this patient population with a focus on outcomes in the neck.

Metastatic Phenotype Is Regulated by Estrogen in Thyroid Cells

BACKGROUND Over 200 million people worldwide are affected by thyroid proliferative diseases, including cancer, adenoma, and goiter, annually. The incidences of thyroid malignancies are three to four times higher in women, suggesting the possible involvement of estrogen. Based on this observed sex bias, we hypothesize that estrogen modulates the growth and metastatic propensity of thyroid cancer cells. METHODS In this study, two thyroid cell lines (Nthy-ori 3-1 and BCPAP) were evaluated for the presence of estrogen receptor (ER) by Western blot analysis and estrogen responsiveness by using a cell proliferation assay. In addition, the effect of estradiol (E(2)) on modulation of metastatic phenotype was determined by using in vitro adhesion, migration, and invasion assays. RESULTS Thyroid cells expressed a functionally active ER-alpha and ER-beta as evidenced by 50-150% enhancement of proliferation in the presence of E(2). E(2) also enhanced adhesion, migration, and invasion of thyroid cells in an in vitro experimental model system that, based on our results, is modulated by beta-catenin. CONCLUSION Our data provide evidence that the higher incidence of thyroid cancer in women is potentially attributed to the presence of a functional ER that participates in cellular processes contributing to enhanced mitogenic, migratory, and invasive properties of thyroid cells. These findings will enable and foster the possible development of antiestrogenic therapy targeting invasion and migration, thus affecting metastatic propensity.

Five-Year Survival Rates and Time Trends of Laryngeal Cancer in the US Population

OBJECTIVES To provide comprehensive temporal trend analysis of 5-year relative survival rates of laryngeal cancer using the Surveillance, Epidemiology, and End Results database; and to expand on prior reports by including inclusion of laryngeal tumor location, stage, age at diagnosis, treatment strategy, and histologic grade. DESIGN Retrospective cohort analysis using the Surveillance, Epidemiology, and End Results database of the National Cancer Institute. The Surveillance, Epidemiology, and End Results data were used to design 5 cohorts of patients with laryngeal cancer: 1977-1978, 1983-1984, 1989-1990, 1995-1996, and 2001-2002. Five-year survival rates were analyzed according to tumor site, stage, and grade; age at diagnosis; and treatment strategy. The joinpoint regression model was used to assess survival trends and their statistical significance. RESULTS Among patients with supraglottic cancer, 5-year relative survival rates for distant disease worsened over time while rates for local and regional disease did not change (P = .01 and P > .05, respectively). For localized glottic cancer, survival remained stable from 1977-1978 to 2001-2002. However, patients with regional and distant glottic cancer demonstrated a significant decrease in survival in the past 3 decades (P < .001). This trend was independent of treatment strategy. Finally, the proportion of well-differentiated tumors in patients with regional laryngeal cancer decreased over time (P < .001 for supraglottic and P = .007 for glottic). CONCLUSIONS A decreasing 5-year survival trend was found among patients with glottic cancer who had regional disease and in all patients with distant disease. Histopathologic trends not previously reported in those with laryngeal cancer seem to parallel those seen in other tobacco-related cancers. These trends may reflect the effect of birth cohorts and implicate the relationship between carcinogenic exposure and host factors, rather than the influence of treatment.

Comparison of GSTM polymorphisms and risk for oral cancer between African-Americans and Caucasians.

Two members of the mu class of glutathione S-transferase (GST) genes, GSTM1 and GSTM3, have polymorphic alleles which have been associated with altered levels of GST mu protein expression and may be linked to increased risk for several tobacco-related cancers. Oral cancer is a tobacco-related disease that affects African-American men at a significantly higher incidence than Caucasian men. To examine the potential role of GSTM polymorphisms in risk for oral cancer in African-Americans and Caucasians, the prevalences of the GSTM1 null and GSTM3 intron 6 polymorphisms were examined in 63 African-American and 101 Caucasian patients with histologically confirmed primary oral cancer, as well as in 133 African-American and 213 Caucasian matched control subjects. In African-Americans, the odds ratio for oral cancer associated with the GSTM1 (0/0) genotype was 3.1 [95% confidence interval (CI) = 1.1-8.5], with the association between the GSTM1 (0/0) genotype and oral cancer risk strongest in heavy smokers [i.e. > 24 pack-years; odds ratio (OR) = 5.4, 95% CI = 1.2-24]. Using the potentially most protective GSTM1 [+]/GSTM3 (B/B) genotype as the reference group, increased risk for oral cancer was observed in African-Americans with the GSTM1 [+]/GSTM3 [(A/A) + (A/B)] (OR = 2.2, 95% CI = 0.82-6.0), GSTM1 (0/0)/GSTM3 (B/B) (OR = 4.3, 95% CI = 1.1-16), and GSTM1 (0/0)/GSTM3 [(A/A) + (A/B)] (OR = 6.6, 95% CI = 1.2-38) genotypes (P < 0.01, trend test). No significant associations were observed between GSTM genotype and oral cancer risk in Caucasians. These results suggest that the GSTM1 null and GSTM3 intron 6 polymorphisms play an important role in risk for oral cancer among African-Americans and implicates the mu class of GSTs as important tobacco carcinogen detoxifying enzymes in this population.