Base-of-tongue cancer: survival, function, and quality of life after external-beam irradiation and brachytherapy.

OBJECTIVE: Base-of-tongue cancer has traditionally been treated by surgical resection followed by radiation therapy. Primary radiation therapy with brachytherapy has recently been proposed as an alternative. In a prior analysis, we found that patients with advanced tongue-base cancer treated by total glossectomy and postoperative radiation therapy can be cured while potentially maintaining good quality of life. Therefore, we designed the current study to assess survival, function, and quality of life in our patients with tongue-base cancer who were treated with primary radiation therapy and brachytherapy with neck dissection as indicated. STUDY DESIGN: Consecutive case series. METHODS: Twenty patients were treated between 1993 and 1997 using the approach just named. The T stages were T1 (3), T2 (10), T3 (6), and T4 (1). The N stages were N0 (3), N1 (3), N2 (11), and N3 (3). At the time of brachytherapy catheter placement, neck dissections were performed in all 14 patients with N2 or N3 disease. Surviving patients completed a functional status survey and quality of life questionnaire. RESULTS: The 3- and 5-year Kaplan-Meier corrected actuarial survival rates were 57% and 38%, respectively. Eight patients remained alive at the time of this writing and completed the functional status survey and quality of life assessment. Function and quality of life were well maintained in patients treated with external-beam irradiation followed by brachytherapy and neck dissection. However, none of our patients with T3 disease had long-term survival. CONCLUSION: Although we do not endorse external-beam irradiation and brachytherapy for advanced tongue-base cancers, this treatment should be strongly considered for patients with T1 or T2 tumors in whom preservation of function and quality of life is a priority.

Clinical experience with HLA-B7 plasmid DNA/lipid complex in advanced squamous cell carcinoma of the head and neck.

OBJECTIVE: To investigate the safety and efficacy of alloantigen plasmid DNA therapy in patients with advanced head and neck squamous cell carcinoma using Allovectin-7 (Vical Inc, San Diego, Calif), a DNA/lipid complex designed to express the class I major histocompatibility complex antigen HLA-B7. DESIGN: Multi-institutional prospective trial. SETTING: Academic medical setting. PATIENTS: A total of 69 patients were enrolled in 3 sequential clinical trials: a single-center phase 1 trial and 2 multicenter phase 2 trials. Eligibility criteria included unresectable squamous cell carcinoma that failed conventional therapy, Karnofsky performance status score of 70 or greater, and no concurrent anticancer or immunosuppressive therapies. INTERVENTION: Patients received 2 biweekly intratumoral injections of 10 microg (phase 1 and first phase 2 trials) or 100 microg (second phase 2 trial) of Allovectin-7 followed by 4 weeks of observation. Patients with stable or responding disease after the observation period were given a second treatment cycle identical to the first. MAIN OUTCOME MEASURES: Patients were assessed for toxic effects, and tumor size was measured after cycles 1 (at 6 weeks) and 2 (at 16 weeks). RESULTS: Allovectin-7 treatment was well tolerated, with no grade 3 or 4 drug-related toxic effects. Of 69 patients treated, 23 (33%) had stable disease or a partial response after the first cycle of treatment and proceeded to the second cycle. After the second cycle, 6 patients had stable disease, 4 had a partial response, and 1 had a complete response. Responses persisted for 21 to 106 weeks. CONCLUSIONS: Intratumoral plasmid DNA immunotherapy for head and neck cancer with Allovectin-7 is safe, and further investigations are planned in patients with less advanced disease, where it could potentially improve patient survival and reduce the need for radical high-morbidity treatments.

African-American and white head and neck carcinoma patients in a university medical center setting. Are treatments provided and are outcomes similar or disparate?

Racial and ethnic disparities occur in many areas of the health care management system in the United States. These disparities include disease incidence, access to health and medical services, treatments provided, and disease outcomes. Health care delivery organizations have limited resources. Encounters between patients and providers in health care delivery organizations typically are cross-cultural. Access to care, quality of care, and equity may be affected by limited resources and cross-cultural encounters. This impacts the diagnosis, treatments provided, and outcomes, with African-American patients faring poorly compared with white patients. African Americans are 15% more likely to develop cancer than whites and are about 34% more likely to die of cancer than whites in the United States. The purpose of this study was to determine and compare the characteristics of African-American patients and white patients with carcinoma of the head and neck at the University of Cincinnati Medical Center, an equal-access facility, reporting similarities and disparities in disease stage at the time of diagnosis, treatment received, and patient outcomes.

Centrosome hyperamplification in head and neck squamous cell carcinoma: a potential phenotypic marker of tumor aggressiveness.

OBJECTIVES/HYPOTHESIS: There is currently no single histological or genotypic marker that reliably predicts the biological behavior of head and neck squamous cell carcinoma (HNSCC). While multiple genetic mutations have been investigated, no single genotypic alteration has consistently correlated with tumor aggressiveness. Phenotypic markers may prove more predictive, because they can represent many different genetic alterations. We investigated the frequency of centrosome hyperamplification in HNSCC and examined its usefulness as a marker for tumor recurrence. STUDY DESIGN: Analysis of archived paraffin blocks using immunohistochemistry. METHODS: Eighteen patients who underwent resection of oral cavity squamous cell carcinoma were reviewed. Ten patients had cancers that recurred locally within 1 year of resection, and 8 patients were tumor free at 5 years. The amount of centrosome hyperamplification in the cancer specimens and all surgical margins was graded as follows: 0, none; 1+, rare hyperamplification; 2+, greater than 10% of cells per high-powered field; and 3 +, greater than 20% of cells per high-powered field. RESULTS: Centrosome hyperamplification was found in 17 of 18 tumors (94%). Grade 2+ or 3+ hyperamplification was found more in cancers that recurred (9 of 10) than in those that did not (3 of 8) and was more prevalent in the histologically normal margins of patients with recurrence (8 of 10) than in those without recurrent cancer (3 of 8). CONCLUSIONS: Our results demonstrate the extremely frequent occurrence of centrosome hyperamplification in HNSCC. Centrosome hyperamplification is a phenotypic marker for HNSCC and can reflect multiple genotypic changes. Its presence in histologically normal margins suggests that it may be useful for analysis of primary tumors and tumor margins.

Hyalinizing spindle cell tumor with giant rosettes--a soft tissue tumor with mesenchymal and neuroendocrine features. An immunohistochemical, ultrastructural, and cytogenetic analysis.

CONTEXT: Hyalinizing spindle cell tumor with giant rosettes is a recently described biphasic neoplasm of soft tissues that shares mesenchymal and neuroendocrine features. Its morphologic structure is distinctive, with the presence of hyalinized paucicellular foci that are termed rosettes. The cells around the latter display positive immunoreactivity for neuroendocrine markers. The small number of cases described to date indicates that they tend to be localized in the extremities. OBJECTIVE: To describe the clinicopathologic features of 2 unusual cases of hyalinizing spindle cell tumor with giant rosettes. METHODS AND RESULTS: One tumor was located in the prestyloid parapharyngeal space and the second in the left thigh. Both tumors were well circumscribed and surrounded by a thin capsule-like fibrous band without infiltrating projections. The rosettes were embedded in a spindle cell proliferation. Immunohistochemical stains showed positive results for S100 protein, synaptophysin, CD57, protein gene product 9.5, and neuron-specific enolase exclusively in the cells palisading the rosettes. These markers were negative in the spindle cell portions of the tumor. The latter were immunoreactive for factor XIIIa, vimentin, HAM56, collagen IV, and CD68. Vimentin was the only marker shared by the rosette-forming cells and the spindle cells. Ultrastructurally, the rosette-forming cells contained neurosecretory granules. This study describes the first cytogenetic analysis in this type of tumor revealing 2 cell lines, both containing a balanced translocation between chromosomes 7 and 16. Follow-up of the patients at 16 and 8 months did not disclose evidence of recurrence. CONCLUSIONS: These 2 new cases increase the awareness of hyalinizing spindle cell tumor with giant rosettes and demonstrate that it is a spindle cell neoplasm of unique cytogenetic rearrangements composed of dendritic, histiocytic, and fibroblastic cells admixed with cells that have neuroendocrine differentiation.

Esthesioneuroblastoma and sinonasal undifferentiated carcinoma: impact of histological grading and clinical staging on survival and prognosis.

OBJECTIVES: Hyams proposed a histological grading system for esthesioneuroblastoma in which grade I tumors have an excellent prognosis and grade IV tumors are uniformly fatal. The Hyams grading system predated advanced craniofacial techniques, extensive use of immunohistochemistry, and the recognition of sinonasal undifferentiated carcinoma (SNUC) as a distinct entity. Therefore we aimed to determine whether Hyams classification is useful in predicting outcome for esthesioneuroblastoma and SNUC. STUDY DESIGN: A retrospective review of cases from 1970 to 1999. METHODS: Twenty-six patients (12 with esthesioneuroblastoma and 14 with SNUC) were reviewed. The Kadish clinical stage was determined, and histopathological slides were reviewed and graded using the Hyams system. RESULTS: Kadish staging was available for 26 patients (2 patients with stage A tumors; 7 with stage B; and 17 with stage C). Of the 8 evaluable patients with Kadish stage A or B tumors, 6 remained disease free for more than 2 years compared with only 5 of the 17 Kadish stage C tumors. Slides were available for Hyams grading in 21 patients (2 patients with grade I tumors; 4 with grade II; 4 with grade III; and 11 with grade IV). Of the 6 patients with Hyams grade I or II tumors, 4 remained disease free for more than 2 years compared with only 4 of the 15 patients with Hyams grade III or IV tumors. Of note, three patients with Kadish stage C tumors (two with esthesioneuroblastoma, one with SNUC) and two patients with Hyams grade IV tumors (one with esthesioneuroblastoma and one with SNUC) survived for more than 5 years. CONCLUSIONS: Both the Hyams grading system and the Kadish staging system can be used as independent predictors of outcome. Although limited by small numbers, the results of this study demonstrate that patients with either advanced clinical stage or pathological grade of esthesioneuroblastoma or SNUC have poor prognosis, but that long-term survival is possible in these patients if aggressive treatment is used.

PRK, a cell cycle gene localized to 8p21, is downregulated in head and neck cancer.

The human PRK gene encodes a protein serine/threonine kinase of the polo family and plays an essential role in regulating meiosis and mitosis. We have previously shown that PRK expression is downregulated in a significant fraction of lung carcinomas. Our current studies reveal that PRK mRNA expression is downregulated in a majority (26 out of 35 patients) of primary head and neck squamous-cell carcinomas (HNSCC) compared with adjacent uninvolved tissues from the same patients, regardless of stage. In addition, PRK transcripts were undetectable in one of the two HNSCC cell lines analyzed. Ectopic expression of PRK, but not a PRK deletion construct, in transformed A549 fibroblast cells suppresses their proliferation. Furthermore, fluorescence in situ hybridization analyses show that the PRK gene localizes to chromosome band 8p21, a region that exhibits a high frequency of loss of heterozygosity in a variety of human cancers, including head and neck cancers, and that is proposed to contain two putative tumor suppressor genes. Considering that PRK plays an important role in the regulation of the G2/M transition and cell cycle progression, our current studies suggest that deregulated expression of PRK may contribute to tumor development. Genes Chromosomes Cancer 27:332-336, 2000.

MMP and TIMP gene expression in head and neck squamous cell carcinomas and adjacent tissues.

OBJECTIVE: To compare the frequency of gene expression of matrix metalloproteinases (MMP) stromelysins -1, -2 and -3 (MMP-3, -10, and -11), matrilysin (MMP-7), MTI-MMP (MMP-14), and of TIMPs (Tissue Inhibitors of MMPs) -1, -2, -3 and -4 in head and neck squamous cell carcinomas with those of matched adjacent normal tissues. MATERIALS AND METHODS: The present study included 20 surgically removed head and neck squamous cell carcinomas, seven of which were accompanied by matched adjacent oral mucosa excised from the border of the specimens outside the tumor area. RNA isolated from tumors and control samples was subjected to RT-PCR using primers specific for MMP-3, -7, -10, -11 and -14 and for TIMPs -1, -2, -3, and -4. RESULTS: Our findings demonstrate that each of the five MMP genes studied were expressed in essentially all the tumors, while the adjacent marginal tissue samples showed a more varied picture: while stromelysin-3 was located to a majority of the marginal samples, matrilysin was expressed in four of seven adjacent samples, stromelysin-1 and MTI-MMP genes were each expressed in three of these samples, and stromelysin-2 transcript was only expressed in two marginal tissue samples. Whereas TIMP-1 and TIMP-2 transcripts were identified in all tumor and adjacent tissue samples studied, TIMP-3 was expressed, albeit often at low levels, in 17 of 20 tumor samples but only in three of seven adjacent tissues. The novel TIMP-4 gene was not expressed at all. CONCLUSIONS: Specific MMP (MMP-3, -7, -10, -14) and TIMP-3 transcripts observed in head and neck squamous cell carcinomas compared to their frequency in specimens of matching tissues provide important information about expression of extracellular matrix degrading enzymes and their tissue inhibitors in head and neck carcinomas.

Surgical management of hard palate malignancies.

OBJECTIVE: A variety of surgical procedures can be used to treat malignancies of the hard palate and inferior maxilla. This study was designed to evaluate the efficacy of alveolectomy, palatectomy, and infrastructure maxillectomy in the treatment of cancers in these areas. METHODS AND MATERIAL: A retrospective review of 50 patients who underwent alveolectomy, palatectomy, or infrastructure maxillectomy from 1971 to 1997 was performed. The pathology of these lesions included squamous cell carcinoma (25), adenoid cystic carcinoma (11), adenocarcinoma (6), and others (8). RESULTS: The 5-year survival rate by Kaplan-Meier analysis for all lesions was 85%. The 5-year survival rate for squamous cell carcinoma was 76%, and that for adenoid cystic carcinoma was 90%. The 10-year survival rate for adenoid cystic carcinoma was 75%. There was minimal morbidity associated with these procedures. DISCUSSION: Alveolectomy, palatectomy, and infrastructure maxillectomy are the procedures of choice for lesions in the region of the hard palate. The differences between these surgical techniques are presented, and indications, contraindications, and results for each technique are discussed.

Management implications of evaluating the N2 and N3 neck after organ preservation therapy.

OBJECTIVES/HYPOTHESIS: To determine if metastatic squamous cell carcinoma with proliferative potential persists in N2 and N3 necks after conventional radiation. STUDY DESIGN: Retrospective case series. MATERIALS AND METHODS: We identified 17 patients from our head and neck tumor database who underwent organ-preserving radiotherapy for primary aerodigestive squamous cell cancer and N2-3 regional metastasis. Archival tissue from these 17 neck specimens was evaluated for routine histopathologic evidence of tumor, as well as immunohistochemically for cytokeratin and Ki-67 activity. An assay for apoptosis was also performed on 10 of the specimens. RESULTS: Routine H&E evaluation suggested metastatic cancer in 11 of 17 irradiated neck specimens. Cytokeratin immunostaining confirmed squamous cell carcinoma in these 11 necks as well as 1 additional specimen that had tested H&E negative. Ki-67 staining demonstrated proliferating tumor in 3 of 17 necks. The apoptosis assay confirmed regions of apoptosis in all of the specimens analyzed. CONCLUSIONS: The discovery of proliferating cancer cells in 3 of 17 irradiated specimens (18%) supports the practice of planned neck dissection after primary radiotherapy for patients with pretherapeutic N2+ metastatic disease.

Variable genetic alterations and survival in head and neck cancer.

OBJECTIVE: To evaluate multiple genetic loci in patients with head and neck cancer to determine if, as in colorectal carcinoma, there is an orderly occurrence of genetic alterations, and if an accumulation of alterations affects patient survival. DESIGN: Cohort study of patients with head and neck cancer in which fresh tissue was retrieved. SETTING: Academic medical center. PATIENTS: Forty-three patients treated surgically for squamous cell carcinoma of the head and neck from 1991 to 1994. MAIN OUTCOME MEASURES: The DNA from tumor and healthy tissue was evaluated for loss of heterozygosity at p53, retinoblastoma, and chromosome 16q and for amplification of cyclin D1. The respective RNA was probed for levels of p53, p 16, p21, and p27 messenger RNA. These findings were compared with tumor stage and patient survival. RESULTS: DNA analysis showed that loss of heterozygosity occurred at p53 in 21% of tumors, at retinoblastoma in 35%, and at 16q in 21%, and that cyclin D1 was amplified in 42%. Messenger RNA levels of the assessed proteins were variably increased and decreased compared with healthy tissues obtained from the same patients with no discernable pattern. There was no correlation between any one of these genetic alterations and overall survival. When patients were analyzed for loss of heterozygosity at p53, retinoblastoma, 16q, or altered cyclin D1 in combination, 19 patients had no detectable alterations, 13 had 1, 6 had 2, and 5 had 3. Single genetic alterations did not affect survival; however, there was a trend toward decreased survival with multiple alterations. The 2-year Kaplan-Meier survival in patients with less than 1 genetic loss was 78% vs 58% in patients with 2 or more losses. CONCLUSIONS: The lack of a pattern of genetic alterations in head and neck cancer demonstrates that its progression can be mediated by a multitude of pathways, complicating its genetic evaluation. Single genetic alterations do not appear to affect survival; however, when multiple alterations are detected-regardless of combination-survival is affected. This observation lends credence to the theory that multiple genetic alterations contribute to cancer progression; however, the lack of a pattern of this genetic change is a significant obstacle to applying genetic findings to routine cancer therapy.

[Tumor biologic prognostic parameters in T1N0M0 squamous cell carcinoma of the oral cavity]. / Tumorbiologische Prognoseparameter beim T1N0M0-Plattenepithelkarzinom der Mundhöhle.

BACKGROUND: Conventional prognostic factors in squamous cell carcinomas are tumor stage, tumor size, evidence of lymph node metastases, extracapsular spread of lymph node metastases, and Broder's grading. Unfortunately these parameters are only of limited value in predicting the biological behavior and ultimately the prognosis of a particular tumor. The present study was conducted for determining objective prognostic factors based on tumor biologic examinations in patients with squamous cell carcinomas of the oral cavity. These parameters were compared to the conventional prognostic factors. PATIENTS AND METHODS: Operative specimens of fourty-two patients who underwent surgery for a squamous cell carcinoma of the oral cavity with clinical TNM stage T1N0M0 were examined. All tumors were radically excised with histologic clear margins, which were confirmed by serial sections. The examinations included morphologic multifactorial tumor front grading, quantitative DNA analysis, and immunohistochemical assessment of proliferation markers (i.e. proliferating cell nuclear antigen [PCNA] and MIB1) and of oncogene products (i.e. p53; nm23). Prognostic significance of particular parameters was evaluated by univariate and multivariate Cox regression models. RESULTS: In clinical follow-up of 70 months on average, 6 patients developed local recurrences and 5 patients lymph node metastases. Three patients died of disease. Tumors which recurred had increased values for 2 c Deviation Index, 5 c Exceeding Rate along with high tumor front grading scores and proliferation scores. Using multivariate Cox regression analysis, parameters which were highly significant for prognosis were 5 c Exceeding Rate, tumor front grading score and PCNA score. None of the clinical parameters achieved statistical significance in the multivariate model. Tumors which recurred had also increased expression rates for p53 and nm23. Nevertheless this was statistically not significant. CONCLUSIONS: Tumor biologic examinations provide important informations about the clinical aggressiveness and ultimately about the prognosis of a particular tumor. Tumors with aggressive behavior can already be identified during initial diagnosis, which has consequences for the therapeutic management of the patients.

Cervical metastases of head and neck squamous cell carcinoma correlate with loss of heterozygosity on chromosome 16q.

To assess the potential involvement of putative tumor suppressors or metastasis suppressors on chromosome 16q in head and neck squamous cell carcinoma (HNSCC), we have examined 42 primary HNSCCs for loss of heterozygosity (LOH) at 16q and correlated these findings with the occurrence of cervical nodal metastases and other clinical parameters. Seven of the 42 (17%) HNSCCs examined displayed LOH at chromosome 16q24. Three of the seven HNSCCs showed LOH at all of the informative loci analyzed along the chromosome arm, whereas the other four showed only loss of a subset of markers. When LOH at 16q was correlated with clinical parameters, there was no significant correlation with age, sex, clinical stage, T stage, N stage or survival. However, there was a correlation between LOH at chromosome 16q24 and involvement of cervical lymph nodes. Of the seven HNSCCs that had lost heterozygosity at 16q24, six had local metastases to lymph nodes indicating that LOH at 16q24 may have predictive value for the metastatic potential of HNSCCs.

Effects of hemimandibulectomy on quality of life.

OBJECTIVE: To assess the quality of life and functional status of patients who have undergone hemimandibulectomy based on the type of reconstructive procedure performed. STUDY DESIGN: Survey, retrospective. METHODS: Twenty-one patients who had undergone hemimandibulectomy and had similar defects were divided into two groups based on the reconstructive technique utilized. Eleven patients were placed in the soft tissue reconstruction group. Ten patients were placed in the mandible reconstruction group. All patients were assessed for: function, utilizing the Performance Status Scale, and quality of life, using a general cancer questionnaire (FACT-G) and a series of questions specific for head and neck cancer patients. RESULTS: Mandible reconstruction produced a perceived better physical appearance (P = .02), better eating ability (P = .04), and a better overall quality of life (P = .002). The mandible reconstruction cohort consistently outscored the soft tissue cohort on all questionnaires. CONCLUSION: Restoration of mandibular continuity after hemimandibulectomy leads to improved function and a superior quality of life in appropriately selected patients.

Alloantigen gene therapy for squamous cell carcinoma of the head and neck: results of a phase-1 trial.

OBJECTIVE: To determine the safety and efficacy of an immunogenic gene therapy using a drug designed to produce expression of a foreign class I major histocompatibility complex protein in patients with head and neck cancer. DESIGN: Phase 1 prospective clinical trial. SETTING: Academic medical setting. PATIENTS: Nine patients with advanced head and neck squamous cell carcinoma who had failed conventional therapy and did not express HLA-B7, a class I major histocompatibility complex protein. INTERVENTION: Patients were treated with Allovectin-7 (Vical Inc, San Diego, Calif) by direct intratumoral injection. Allovectin-7 contains a plasmid complementary DNA complexed with a cationic lipid, which results in expression of HLA-B7. MAIN OUTCOME MEASURES: Patients were assessed for any toxic effects and for any change in tumor volume. Biopsy specimens obtained before and after therapy were evaluated by immunohistochemistry to detect HLA-B7 expression and with the terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay to detect any induction of apoptosis. RESULTS: There were no toxic effects of the gene therapy. In 4 of these 9 patients there was a partial response to treatment, evidenced by a gradual reduction in tumor size. One patient has remained alive for more than 17 months since commencing treatment, with no clinical evidence of disease but with persistent histological evidence of cancer. Analysis of the biopsy specimens from 2 of the patients who responded to therapy demonstrated HLA-B7 expression. The TUNEL assay demonstrated extensive apoptosis in both of these patients, suggesting that this may be the mechanism of tumor reduction. CONCLUSIONS: These data demonstrate the potential efficacy and lack of toxicity of this form of alloantigen gene therapy. A multi-institutional study has been initiated to expand on these findings.

Tracheal chondrosarcoma: a case report.

BACKGROUND: Tracheal neoplasms are extremely rare, representing only 0.2% of malignancies of the respiratory tract. A case of tracheal chondrosarcoma, with airway obstruction, seen in the Department of Otolaryngology Head and Neck Surgery at the University of Cincinnati is presented. Review of the literature was undertaken, revealing 10 previously described cases. Clinical presentation and treatment options are described. METHODS: A literature review of all reports of tracheal chondrosarcoma was undertaken. RESULTS: From this review, we identified only 10 single case reports. The majority of patients were elderly men, with lesions in the mid to distal trachea. Treatment predominantly consisted of tracheal resection. Recurrence was associated with failure to achieve complete resection. CONCLUSIONS: We conclude that tracheal chondrosarcoma is an exceedingly rare upper airway neoplasm. Treatment should be aimed at complete surgical removal.

Angiogenic inhibition for the treatment of head and neck cancer.

Tumor angiogenesis is a fundamental step in tumor growth and proliferation. Fumagillin is an anti-angiogenic agent which is secreted by Aspergillus, but is also toxic. A fumagillin analogue, TNP-470, has been developed which is a potent angiogenic inhibitor with few side effects. TNP-470 has inhibited tumor growth in Lewis lung cancer and melanoma in animal models. This study was designed to test this proven anti-angiogenic agent's effects on head and neck cancer growth. Fort,v Harlan nude mice were injected subcutaneously with cancer cells from a human oral squamous cell carcinoma. After 3 weeks of tumor growth 25 mice were injected with TNP-470 subcutaneously at a distant site every other day for 30 days while 10 control mice received saline injections. Five mice began TNP-470 injections at the time of tumor injection to determine if TNP-470 can prevent tumor development. The tumor growth and development was unaffected by TNP-470 as compared to the control group. Therefore, the use of an angiogenic inhibitor had no effect on oral cancer growth. Analysis of the cell line utilized found abnormal mRNA expression, which included high p53 expression and low cyclin Dl expression. These results suggest that oral cancers are less dependent on angiogenesis than other tumor types. The genetic abnormalities may explain the angiogenesis independence that was demonstrated. Results found in other tumor types with angiogenic inhibitors cannot be extrapolated to oral cancer since genetic mutations may allow oral tumors to grow without neovascularization.

Surgical management of early-stage hypopharyngeal carcinoma.

There is little consensus regarding the extent of surgical ablation that is needed to attain cure in early-stage hypopharyngeal carcinoma (HPC). To determine effective surgical management of early-stage HPC, we retrospectively reviewed all cases of stage I or stage II HPC treated at our institution between 1970 and 1992. Of 305 patients identified with HPC, 50 (16%) had stage I (N = 13) or stage II (N = 37) cancer at diagnosis. Thirty-seven of the 50 (74%) underwent surgery alone or combined with preoperative or postoperative radiotherapy (RT). Patients were divided into three surgical groups. Group 1 underwent partial pharyngectomy (N = 9), group 2 underwent total laryngectomy and partial pharyngectomy (N = 17), and group 3 underwent total laryngopharyngectomy with cervical esophagectomy and reconstruction (N = 11). Overall and disease-specific survivals were determined from Kaplan-Meier survival analysis. Disease-free 5-year survival in stage I and II HPCs was 40.1%. Univariate analysis showed a statistically significant decrease in survival for patients undergoing partial pharyngectomy when compared with those undergoing more extensive procedures (p < .03). This was confirmed with multivariate loglogistic regression analysis (p < .03) correcting for confounding variables of site and RT. These data suggest that wide resection improves disease-free survival in patients with early-stage HPC.