Genetic heterogeneity in saliva from patients with oral squamous carcinomas: implications in molecular diagnosis and screening.

We performed microsatellite analysis at chromosomal regions frequently altered in head and neck squamous carcinoma on matched saliva and tumor samples from 37 patients who had oral squamous carcinoma. The results were correlated with the cytologic findings and traditional clinicopathologic factors to assess the diagnostic and biological potential of these markers. Our data showed that 18 (49%) of the saliva samples and 32 (86%) of the tumors had loss of heterozygosity (LOH) in at least one of the 25 markers studied. In saliva, the combination of markers D3S1234, D9S156, and D17S799 identified 13 (72.2%) of the 18 patients with LOH in saliva (P < 0.001). For tumors, markers D3S1234, D8S254, and D9S171 together identified 27 (84.3%) of the 32 tumors with LOH at any of the loci tested (P < 0.001). Eleven (55%) of the 20 saliva samples with cytologic atypia and seven (35%) of the 17 specimens without atypia had LOH. Significant correlation between LOH in tumor at certain markers and smoking and alcohol use was found. Our results indicate that: 1) epithelial cells in saliva from patients with head and neck squamous tumorigenesis provide suitable material for genetic analysis; 2) combined application of certain markers improves the detection of genetic alteration in these patients; 3) clonal heterogeneity between saliva and matching tumor supports genetic instability of the mucosal field in some of these patients; and 4) LOH at certain chromosomal loci appears to be associated with smoking and alcohol consumption.

Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer.

PURPOSE: A multi-institutional, prospective, randomized trial was undertaken in patients with advanced head-and-neck squamous cell carcinoma to address (1) the validity of using pathologic risk features, established from a previous study, to determine the need for, and dose of, postoperative radiotherapy (PORT); (2) the impact of accelerating PORT using a concomitant boost schedule; and (3) the importance of the overall combined treatment duration on the treatment outcome. METHODS AND MATERIALS: Of 288 consecutive patients with advanced disease registered preoperatively, 213 fulfilled the trial criteria and went on to receive therapy predicated on a set of pathologic risk features: no PORT for the low-risk group (n = 31); 57.6 Gy during 6.5 weeks for the intermediate-risk group (n = 31); and, by random assignment, 63 Gy during 5 weeks (n = 76) or 7 weeks (n = 75) for the high-risk group. Patients were irradiated with standard techniques appropriate to the site of disease and likely areas of spread. The study end points were locoregional control (LRC), survival, and morbidity. RESULTS: Patients with low or intermediate risks had significantly higher LRC and survival rates than those with high-risk features (p = 0.003 and p = 0.0001, respectively), despite receiving no PORT or lower dose PORT, respectively. For high-risk patients, a trend toward higher LRC and survival rates was noted when PORT was delivered in 5 rather than 7 weeks. A prolonged interval between surgery and PORT in the 7-week schedule was associated with significantly lower LRC (p = 0.03) and survival (p = 0.01) rates. Consequently, the cumulative duration of combined therapy had a significant impact on the LRC (p = 0.005) and survival (p = 0.03) rates. A 2-week reduction in the PORT duration by using the concomitant boost technique did not increase the late treatment toxicity. CONCLUSIONS: This Phase III trial established the power of risk assessment using pathologic features in determining the need for, and dose of, PORT in patients with advanced head-and-neck squamous cell cancer in a prospective, multi-institutional setting. It also revealed the impact of the overall treatment time in the combination of surgery and PORT on the outcome in high-risk patients and showed that PORT acceleration without a reduction in dose by a concomitant boost regimen did not increase the late complication rate. These findings emphasize the importance of coordinated interdisciplinary care in the delivery of combined surgery and RT.

The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial.

Second primary tumors (SPTs) develop at an annual rate of 3-7% in patients with head and neck squamous cell cancer (HNSCC). In a previous Phase III study, we observed that high doses of 13-cis-retinoic acid reduced the SPT rate in this disease. In 1991, we launched an intergroup, placebo-controlled, double-blind study to evaluate the efficacy of low-dose 13-cis-retinoic acid in the prevention of SPTs in patients with stage I or II squamous cell carcinoma of the larynx, oral cavity, or pharynx who had been previously successfully treated with surgery, radiotherapy, or both, and whose diagnoses had been established within 36 months of study entry. As of September 16, 1999, the Retinoid Head and Neck Second Primary (HNSP) Trial had completed accrual with 1384 registered patients and 1191 patients randomized and eligible. All of the patients were followed for survival, SPT development, and index cancer recurrence. Smoking status was assessed at study entry and during study. Smoking cessation was confirmed biochemically by measurement of serum cotinine levels. The annual rate of SPT development was analyzed in terms of smoking status and tumor stage. As of May 1, 2000, SPTs have developed in 172 patients. Of these, 121 (70.3%) were tobacco-related SPTs, including 113 in the aerodigestive tract (57 lung SPTs, 50 HNSCC SPTs, and 6 esophageal SPTs) and 8 bladder SPTs. The remaining 51 cases included 23 prostate adenocarcinomas, 8 gastrointestinal malignancies, 6 breast cancers, 3 melanomas, and 11 other cancers. The annual rate of SPT development observed in our study has been 5.1%. SPT development related to smoking status was marginally significant (active versus never, 5.7% versus 3.5%; P = 0.053). Significantly different smoking-related SPT development rates were observed in current, former, and never smokers (annual rate = 4.2%, 3.2%, and 1.9%, respectively, overall P = 0.034; current versus never smokers, P = 0.018). Stage II HNSCC had a higher overall annual rate of SPT development (6.4%) than did stage I disease (4.3%; P = 0.004). When evaluating the development of smoking-related SPTs, stage was also highly significant (4.8% for stage II versus 2.7% for stage I; P = 0.001). Smoking-related SPT incidence was significant for site as well (larynx versus oral cavity, P = 0.015; larynx versus pharynx, P = 0.011). Primary tumors recurred at an annual rate of 2.8% in a total of 97 patients. The rate of recurrence was higher in patients with stage II disease (4.1% versus 2.2%, P = 0.004) as well as oral cavity site when compared with larynx (P = 0.002). This is the first large-scale prospective chemoprevention study evaluating smoking status and its impact on SPT development and recurrence rate in HNSCC. The results indicate significantly higher SPT rates in active smokers versus never smokers and significantly higher smoking-related SPT rates in active smokers versus never smokers, with intermediate rates for former smokers.

The development and validation of a dysphagia-specific quality-of-life questionnaire for patients with head and neck cancer: the M. D. Anderson dysphagia inventory.

OBJECTIVE: To design a reliable and validated self-administered questionnaire whose purpose is to assess dysphagia's effects on the quality of life (QOL) of patients with head and neck cancer. DESIGN: Cross-sectional survey study. METHODS: Focus groups were convened for questionnaire development and design. The M. D. Anderson Dysphagia Inventory (MDADI) included global, emotional, functional, and physical subscales. One hundred consecutive adult patients with a neoplasm of the upper aerodigestive tract who underwent evaluation by our Speech Pathology team completed the MDADI and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Speech pathologists completed the Performance Status Scale for each patient. Validity and reliability properties were calculated. Analysis of variance was used to assess how well the MDADI discriminated between groups of patients. RESULTS: The internal consistency reliability of the MDADI was calculated using the Cronbach alpha coefficient. The Cronbach alpha coefficients of the MDADI subscales ranged from 0.85 to 0.93. Test-retest reliability coefficients of the subscales ranged from 0.69 to 0.88. Spearman correlation coefficients between the MDADI subscales and the SF-36 subscales demonstrated construct validity. Patients with primary tumors of the oral cavity and oropharynx had significantly greater swallowing disability with an adverse impact on their QOL compared with patients with primary tumors of the larynx and hypopharynx (P<.001). Patients with a malignant lesion also had significantly greater disability than patients with a benign lesion (P<.001). CONCLUSIONS: The MDADI is the first validated and reliable self-administered questionnaire designed specifically for evaluating the impact of dysphagia on the QOL of patients with head and neck cancer. Standardized questionnaires that measure patients' QOL offer a means for demonstrating treatment impact and improving medical care. The development and validation of the MDADI and its use in prospective clinical trials allow for better understanding of the impact of treatment of head and neck cancer on swallowing and of swallowing difficulty on patients' QOL.

The development of breast carcinoma in women with thyroid carcinoma.

BACKGROUND: Breast carcinoma and thyroid carcinoma are two malignancies that occur most commonly in women. An association between the incidence rates of thyroid and breast carcinoma in women after a diagnosis of the other malignancy has been suggested in a retrospective analysis of a single institution's tumor registry. In that study, an increased incidence of breast carcinoma in premenopausal women previously treated for thyroid carcinoma was observed. METHODS: The purpose of this study was to investigate further this relation utilizing a large database, the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database. The SEER database is maintained by the National Cancer Institute, and it represents 11 population-based cancer registries covering approximately 14% of the United States population. The study was a population-based retrospective cohort analysis using external comparisons. From 1973 to 1994, 365 women in the SEER database were identified as having both thyroid and breast carcinomas. The SEER database from 1973 to 1994 was utilized to calculate age specific and calendar year specific incidence rates for each year for thyroid and breast carcinomas. The expected number of second cancers for each age group, calendar year, and follow-up period were determined by multiplying these incidence rates by the age specific and calendar year specific number of person-years at risk. The risk ratio (RR) was calculated by dividing the observed by the expected number of second cancers. Statistical significance was determined by the Poisson test. RESULTS: A total of 1,333,115 person-years were available for analysis. One hundred thirteen thyroid carcinoma cases were diagnosed after breast carcinoma cases (RR, 0.99; P = 0.576). Two hundred fifty-two breast carcinoma cases were diagnosed after thyroid carcinoma cases (RR, 1.18; P = 0.007). Premenopausal women (age 20-49 years) with an index thyroid carcinoma have a significantly increased risk of developing subsequent breast carcinoma (RR, 1.42; P = 0.001). Black premenopausal women with an index thyroid carcinoma do not have an increased risk of developing breast carcinoma, but the statistical power is lower due to low numbers. No women with index breast carcinoma have an increased risk of developing thyroid carcinoma. CONCLUSIONS: Women with a history of thyroid carcinoma have a greater than expected risk of developing breast carcinoma. This risk is most pronounced in premenopausal white women. The implications of this observation with respect to breast carcinoma screening guidelines and thyroid carcinoma treatment guidelines deserve further investigation.

The significance of comorbidity in advanced laryngeal cancer.

INTRODUCTION: Cancer patients often have concurrent diseases and conditions known as comorbidities. The aim of this project is to demonstrate the significance of comorbidity in the treatment and outcomes of advanced laryngeal carcinoma. METHODS: A retrospective medical record review of 182 patients with previously untreated T3 or T4 squamous carcinomas of the larynx treated at M. D. Anderson between 1990 and 1995 was performed. Demographic, patient-specific, tumor-specific, and outcome measures information were collected. Comorbidity was coded using the Modified Medical Comorbidity Index. Univariate and multivariate analysis with the use of life survival analysis techniques and logistic regression were performed. RESULTS: The median age at diagnosis was 59.5 years. Most patients were men (69.2%) and Caucasian (73.1%). Laryngeal preservation was performed in 90 patients, and surgical resection was performed in 92 patients. Patients in the two treatment groups had similar comorbidity, locoregional control (65%), and 5-year survival (37.3%). Patients with either moderate or severe comorbidity had significantly worse overall survival (p = .00014) and worse 5-year survival than those with no or mild comorbidity (21.8% vs 46.3%, p = .003). CONCLUSIONS: This study demonstrates that comorbidity is significantly associated with survival in a group of patients with identical histology, site, and stage. Comorbid status should be incorporated into the assessment of prognosis and outcome to improve and optimize the management of head and neck cancer patients.

Combined interferon-alfa, 13-cis-retinoic acid, and alpha-tocopherol in locally advanced head and neck squamous cell carcinoma: novel bioadjuvant phase II trial.

PURPOSE: Retinoids and interferons (IFNs) have single-agent and synergistic combined effects in modulating cell proliferation, differentiation, and apoptosis in vitro and clinical activity in vivo in the head and neck and other sites. Alpha-tocopherol has chemopreventive activity in the head and neck and may decrease 13-cis-retinoic acid (13-cRA) toxicity. We designed the present phase II adjuvant trial to prevent recurrence or second primary tumors (SPTs) using 13-cRA, IFN-alpha, and alpha-tocopherol in locally advanced-stage head and neck cancer. PATIENTS AND METHODS: After definitive local treatment with surgery, radiotherapy, or both, patients with locally advanced SCCHN were treated with 13-cRA (50 mg/m(2)/d, orally, daily), IFN-alpha (3 x 10(6) IU/m(2), subcutaneous injection, three times a week), and alpha-tocopherol (1,200 IU/d, orally, daily) for 12 months, with a dose modification. Screening for recurrence or SPTs was performed every 3 months. RESULTS: Tumors of 11 (24%) of the 45 treated patients were stage III, and 34 (76%) were stage IV. Thirty-eight (86%) of 44 patients completed the full 12-month treatment (doses modified as needed). Toxicity generally was consistent with previous IFN and 13-cRA reports and included mild to moderate mucocutaneous and flu-like symptoms; occasional significant fatigue (grade 3 in 7% of patients), mild to moderate hypertriglyceridemia in 30% of patients who continued treatment along with antilipid therapy, and mild hematologic side effects. Six patients did not complete the planned treatment because of intolerable toxicity or social problems. At a median 24-months of follow-up, our clinical end point rates were 9% for local/regional recurrence (four patients), 5% for local/regional recurrence and distant metastases (two patients), and 2% for SPT (one patient), which was acute promyelocytic leukemia (ie, not of the upper aerodigestive tract). Median 1- and 2-year rates of overall survival were 98% and 91%, respectively, and of disease-free survival were 91% and 84%, respectively. CONCLUSION: The novel biologic agent combination of IFN-alpha, 13-cRA, and alpha-tocopherol was generally well tolerated and promising as adjuvant therapy for locally advanced squamous cell carcinoma of the head and neck. We are currently conducting a phase III randomized study of this combination (v no treatment) to confirm these phase II study results.

Merkel cell carcinoma of the head and neck: effect of surgical excision and radiation on recurrence and survival.

BACKGROUND: Merkel cell carcinoma is a rare malignant neoplasm of the skin that most often arises in the head and neck region. Despite the innocuous appearance of the primary lesion, Merkel cell carcinoma often has an aggressive clinical course with frequent locoregional recurrences and distant metastases. We evaluated the association of the width of surgical margins and the use of postoperative radiation therapy with locoregional control and survival rates. METHODS: The medical records of 66 patients with head and neck Merkel cell carcinoma seen between 1945 and 1995 were retrospectively reviewed. The Fisher exact test was used to compare outcomes. Kaplan-Meier survival curves were constructed. RESULTS: Eighteen patients for whom there was adequate information were divided into the following groups according to the width of their surgical margins: smaller than 1 cm, 1 to 2 cm, and larger than 2 cm. No statistical difference in locoregional control or survival was found among these groups owing to the small patient population. In contrast, a comparison of the patients who did (n = 26) and did not (n = 34) receive postoperative radiation therapy revealed a significant difference in local (3 [12%] vs 15 [44%], respectively; P<.01) and regional (7 [27%] vs 29 [85%], respectively; P<.01) recurrence rates. There was, however, no significant difference in the disease-specific survival between these groups (P = .30). Distant disease developed in 36% of all patients regardless of therapy. CONCLUSIONS: Any effect of the width of surgical margins on outcome was not detectable in the small number of patients analyzed. The use of postoperative radiation therapy was associated with a significant improvement in locoregional control. There was no detectable influence of the type of initial therapy on the rates of distant metastases or on survival. Future therapeutic innovations should be directed toward controlling the development of distant metastases in patients with Merkel cell carcinoma.

Squamous cell carcinoma with perineural invasion presenting as a Tolosa-Hunt-like syndrome: a potential pitfall in diagnosis.

PURPOSE: To describe a case of perineural invasion resulting from squamous cell carcinoma of forehead. METHODS: Case report. RESULTS: Perineural invasion resulting from squamous cell carcinoma of the periocular skin can present as a Tolosa-Hunt-like syndrome with lack of radiologic findings on magnetic resonance imaging (MRI) in its early stages. CONCLUSION: A high level of suspicion for perineural invasion is required when assessing multiple cranial nerve palsies in patients with a history of cutaneous malignancy, despite negative sequential MRI. Perineural invasion must be ruled out by a biopsy of the involved nerves, whenever possible, before empiric therapy with systemic steroids is contemplated.

Loss of imprinting and genetic alterations of the cyclin-dependent kinase inhibitor p57KIP2 gene in head and neck squamous cell carcinoma.

The p57KIP2 is a maternally expressed and paternally imprinted cyclin-dependent kinase inhibitor located on chromosome 11p15.5. Because of its location, biochemical functions, and imprinting status, p57KIP2 has been considered a candidate tumor suppressor gene. To determine, for the first time, the involvement of this gene in the development of head and neck squamous carcinoma (HNSC), we analyzed the imprinting and expression status and loss of heterozygosity (LOH) within the p57KIP2 gene flanking loci on the 11p15.5 region in 64 primary untreated tumors. Of the 30 (47%) informative cases for this gene, loss of imprinting and LOH were noted in 4 (13%) and 10 tumors (33%), respectively. Analysis of the microsatellite markers flanking the p57KIP2 gene on chromosome 11p showed infrequent alterations at these loci. p57KIP2 was expressed in all tumors with LOH within and around the gene. Quantitative reverse transcription-PCR analysis showed elevated p57 mRNA expression in tumor with loss of imprinting. Sequencing analysis of exons 1 and 2 of the p57KIP gene failed to detect any mutations. Our data indicate: (a) infrequent genomic abnormalities at the p57KIP2 gene in HNSC; (b) leaky or incomplete imprinting of the paternal allele is associated with increased expression of this gene in a subset of tumors; and (c) minimal evidence for suppressor function for this gene in HNSC.

Prognostic factors for survival in malignant melanoma of the eyelid skin.

PURPOSE: This study aimed to determine the prognostic factors for survival and disease-free interval for malignant melanoma of the eyelid skin. METHODS: This was a retrospective, nonrandomized, clinical review. Twenty-four patients with eyelid skin melanoma were identified through a search of the tumor registry at M. D. Anderson Cancer Center. Patients were treated between 1953 and 1994. The follow-up ranged from 3 to 18 years (mean = 9.6 years). Primary treatment in all cases entailed wide local excision of the tumor. Patients in whom regional lymph node metastasis developed underwent parotidectomy or neck dissection, with or without adjuvant chemotherapy or external beam radiation. Descriptive statistics were used to characterize the patients. Survival analysis in terms of disease-free survival and recurrence-free survival was performed using age, sex, location of tumor (upper lid, lower lid, or both), histologic type of melanoma, Breslow thickness, and Clark's level as independent variables for survival. RESULTS: Age, sex, location, and the histologic type of tumor were not significant prognostic indicators for survival in this cohort. Clark's level > or = IV by itself was a statistically significant predictor of decreased survival. In addition, tumors with either Clark's level > or = IV or Breslow thickness > or = 1.5 mm were associated with increased mortality. CONCLUSION: Clark's level > or = IV or Breslow thickness > or = 1.5 mm are poor prognostic indicators for malignant melanomas of the eyelid skin. Clinicians should have a high level of suspicion for occult regional lymph node metastasis when treating patients with these tumor features.

Extent of surgery for intermediate-risk well-differentiated thyroid cancer.

BACKGROUND: Methods of assigning patients with papillary or follicular thyroid cancer (well-differentiated thyroid cancer) to risk groups for the purpose of determining appropriate therapy have been developed. Despite these efforts, the optimal extent of surgery for intermediate-risk patients remains controversial. METHODS: A retrospective study was conducted of 208 patients with well-differentiated thyroid cancer (DTC) from two institutions. Univariate and multivariate analysis of patient- and tumor-related variables was performed. A regression model was obtained, three risk groups (low, intermediate, and high) were defined, and survival curves were generated. RESULTS: Prognostic variables were age (P <0.001), distant metastases (P <0.001), tumor size (P <0.001) and an aggressive growth pattern (P = 0.03) by univariate analysis and age (P <0.001) and distant metastases (P <0.001) by multivariate analysis. Tumor size (P = 0.07) was included in the regression model. Total thyroidectomy appeared to provide a survival advantage for intermediate risk patients. High-risk patients treated by lobectomy had a poorer prognosis. CONCLUSIONS: Total thyroidectomy may provide a survival advantage for intermediate-risk patients with DTC. A prospective randomized trial with 200 such patients is required to confirm this finding.

The impact of clinical pathways on the practice of head and neck oncologic surgery: the University of Texas M. D. Anderson Cancer Center Experience.

OBJECTIVE: To assess the impact of clinical pathways on the practice of head and neck oncologic surgery in an academic center. DESIGN: Cross-sectional study. SETTING: Cancer treatment center. PATIENTS: The study population consisted of 3 groups of patients who underwent unilateral neck dissection and were treated in the Department of Head and Neck Surgery of the University of Texas M. D. Anderson Cancer Center, Houston. Additional procedures which may have been performed were direct laryngoscopy, rigid esophagoscopy, and/or dental extractions. Ninety-six patients treated during 1993-1994 prior to the implementation of the clinical pathway (historical control group) were compared with 94 patients treated during 1996-1998, 64 who were not (contemporaneous nonpathway group) and 30 who were managed on the clinical pathway (pathway group). Patients from 1995 were excluded since the pathway was in the planning stages then. MAIN OUTCOME MEASURES: Median length of stay; median total costs of care. RESULTS: The median length of hospital stay of the historical control, contemporaneous nonpathway, and pathway groups decreased from 4.0 to 2.0 days (P<.001). The total median costs of care were less in the pathway group as compared with the historical control group ($6,227 and $8,459, respectively, P<.001) and also less in the contemporaneous nonpathway group compared with the historical control group (S6885 and $8,459, respectively, P<.001). Mean and median length of hospital stay and costs were lower in the pathway group as compared with the nonpathway group but not significantly (P = .11 and P = .07, respectively) The contemporaneous nonpathway and pathway groups did not differ in complications or readmissions. CONCLUSIONS: Development and implementation of this clinical pathway played a statistically significant role in decreasing length of hospital stay and total costs of care associated with neck dissection between nonpathway and pathway patients. Thus, a more cost-effective practice environment has resulted for all of our patients.

Frequent loss of imprinting at the IGF2 and H19 genes in head and neck squamous carcinoma.

Genomic imprinting is an inherited epigenetic phenomenon that results in parental-origin-specific gene expression in somatic cells. Relaxation or loss of this feature in certain genes has been demonstrated in several pediatric and adult neoplasms, suggesting an association with tumorigenesis. We analysed 64 primary untreated head and neck squamous carcinoma for the loss of imprinting in the IGF2 and H19 genes to determine the implications of this alteration in the development and progression of these tumors. Forty-nine (77%) of the 64 tumors were informative for imprinting analyses of these genes. IGF2 and H19 were imprinted in all normal squamous epithelium examined. Twelve (37.5%) of 32 tumors informative for H19 and 11 (40.7%) of 27 tumors informative for IGF2 manifested loss of imprinting. Ten tumors were informative for both genes, of which four maintained the constitutional imprinting and six showed loss of imprinting at either H19 or IGF2. These data suggest that loss of imprinting at the IGF2 and H19 loci play a role in the oncogenesis of head and neck carcinoma.

Phase I/II trial of radiation with chemotherapy "boost" for advanced squamous cell carcinomas of the head and neck: toxicities and responses.

PURPOSE: Extrapolating from our experience delivering a "boost" field of radiation concurrently with fields treating both gross and subclinical disease at the end of a course of radiation therapy, we developed a regimen to deliver concurrent chemotherapy during the last 2 weeks of a conventionally fractionated course of radiation. PATIENTS AND METHODS: Patients had stage III or IV biopsy-proven squamous cell carcinoma originating from a head and neck mucosal site. The regimen was 70 Gy delivered over 7 weeks with concurrent fluorouracil (5-FU) and cisplatin given daily with each radiation dose during the last 2 weeks. A phase I study was performed to determine the maximum-tolerated dose (MTD) before a phase II study was conducted. RESULTS: The MTD was 400 mg/m(2) per day for 5-FU and 10 mg/m(2) per day for cisplatin. Mucositis persisting more than 6 weeks after therapy was the dose-limiting toxicity. A total of 60 patients were treated on the two phases of the study. Eighteen patients (35%) treated at the MTD developed prolonged mucositis. There were two cases of neutropenic sepsis, including one fatality. The actuarial 2-year rates for overall survival, freedom from relapse, and local control were 62%, 59%, and 80%, respectively. CONCLUSION: Preliminary locoregional control rates seem to be higher than those reported for treatment with radiation alone. Toxicity was also greater than that seen with radiation alone, but the regimen was designed to deliver an intense treatment schedule, which could be completed without significant interruptions, and to obtain high control rates above the clavicles. These end points were achieved.

Biochemoprevention for dysplastic lesions of the upper aerodigestive tract.

OBJECTIVES: To evaluate the efficacy and secondarily the toxic effects of biochemopreventive therapy (high-dose isotretinoin [13-cis-retinoic acid], alpha-tocopherol, and interferon alfa) in the reversal of advanced premalignant lesions of the upper aerodigestive tract and to correlate the therapeutic events with modulation of biomarkers. DESIGN: Prospective, nonrandomized chemoprevention trial. SETTING: Tertiary cancer care referral center and ambulatory care. PARTICIPANTS: Thirty-six patients with advanced premalignant lesions of the upper aerodigestive tract, without cancer during the 2 years before the intervention, with evaluable lesions, and without retinoid therapy for 3 months before the trial. INTERVENTION: Administration of oral isotretinoin (100 mg/m2 per day), oral alpha-tocopherol (1200 IU/d), and subcutaneous interferon alfa (3 megaunits per square meter twice weekly) for 12 months, with serial biopsies and clinical examination at 0, 6, 12, and 18 months from study start. MAIN OUTCOME MEASURES: Clinical and histologic responses to the intervention. RESULTS: Of the 36 patients, evaluation was possible in 30 for response at 6 months and in 21 at 12 months. At 6 months, there were 10 pathologic complete responses and 7 partial responses; at 12 months, 7 complete and 3 partial responses. A striking difference in response was observed in favor of laryngeal lesions (9/19 [47%] complete response rate at 6 months and 7/14 [50%] at 12 months vs 1/11 [9%] and 0/7 [0%], respectively, for oral lesions). Toxic effects were acceptable and did not exceed grade 3. CONCLUSION: Biochemoprevention is a promising biologic approach for laryngeal dysplasia and needs to be investigated further.

Selective neck dissections for squamous carcinoma of the upper aerodigestive tract: patterns of regional failure.

BACKGROUND: Surgeons have been using selective neck dissections in the treatment of squamous carcinoma of the upper aerodigestive tract for over 20 years. To date, no data is available that can answer the question "What are the patterns of failure in the neck following a selective neck dissection and is a selective neck dissection a reliable procedure for metastatic disease?" METHODS: To answer this question, the medical records of all patients with squamous carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx treated at The University of Texas M. D. Anderson Cancer Center from January 1, 1985-December 31, 1990, with a selective neck dissection were reviewed. Five hundred seventeen neck dissections were analyzed: suprahyoid (41), supraomohyoid (284), and anterolateral (192). The end point of the study was regional failure and survival. RESULTS: Regional recurrence in patients treated with a suprahyoid dissection was 43% with pathologically positive nodes. The regional recurrence in the patients treated with a supraomohyoid neck dissection was 1.9% with pathologically negative nodes, 35.7% with path N1 without postoperative radiation therapy, and 5.6% with postoperative radiation therapy. The neck staged pathologically N2B failed with and without postoperative radiation, 8.3% and 14%, respectively. Thirteen percent of the anterior/lateral neck dissections failed regionally. If multiple pathologically positive nodes (N2B) were present, the regional failure with postoperative radiation was 30% and 33.3% without postoperative radiation. CONCLUSION: The results of this retrospective study suggest that a selective neck dissection is a satisfactory staging procedure and is a definitive operation if all the nodes are pathologically negative. However, if a node is found to be invaded with cancer, the use of postoperative radiation is advisable.