Biomedical subjects
Publications and source records attributed to Ashok R Shaha.
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OBJECTIVE: To identify the impact of referral guidelines for head and neck cancer on the economics and effectiveness of the delivery of care. METHODS: A retrospective review of the literature was performed to examine the current referral guidelines and referral models that have impacted the delivery of care. RESULTS: Advances in technology and changes in the diagnostic work up of head and neck cancer require that common symptoms and presentations of head and neck cancer are made available to primary care physicians to improve the expeditious referral of head and neck cancer patients. CONCLUSION: Physician awareness and symptom guidelines may prove effective in expediting the care of patients with head and neck cancer.
PURPOSE: Intensity-modulated radiation therapy (IMRT) enables highly conformal treatment for thyroid cancer (TC). In this study, we review outcomes/toxicity in a series of TC patients treated with IMRT. METHODS AND MATERIALS: Between July 2001 and January 2004, 20 nonanaplastic TC patients underwent IMRT. Mean age was 55. There were 3 T2 and 17 T4 patients. Sixteen patients had N1 disease. Seven patients had metastases before RT. Fifteen underwent surgery before RT. Radioactive iodine (RAI) and chemotherapy were used in 70% and 40%, respectively. Median total RT dose was 63 Gy. RESULTS: With two local failures, 2-year local progression-free rate was 85%. There were six deaths, with a 2-year overall survival rate of 60%. For patients with M0 disease, the 2-year distant metastases-free rate was 46%. The worst acute mucositis and pharyngitis was Grade 3 (n = 7 and 3, respectively). Two patients had Grade 3 acute skin toxicity and 2 had Grade 3 acute laryngeal toxicity. No significant radiation-related late effects were reported. CONCLUSIONS: IMRT for TC is feasible and effective in appropriately selected cases. Acute toxicity is manageable with proactive clinical care. Ideal planning target volume doses have yet to be determined. Additional patients and long-term follow-up are needed to confirm these preliminary findings and to clarify late toxicities.
For patients with squamous cell carcinoma of the upper aerodigestive tract, appropriate management of the regional lymph nodes is an important and often controversial issue that has significant influence on survival. Over the years radical treatment either by surgery or radiotherapy contributed to improvement in prognosis. Recently, a more conservative approach has achieved a similar level of cancer control with less morbidity. This review considers the issues of selection of patients for treatment of the neck, choice of modality and extent of therapy, treatment of the contralateral neck, management of recurrence and influence of the site and status of the primary lesion.
Selective neck dissection is a modification of the more comprehensive modified radical or radical neck dissection that is designed to remove only those nodal levels considered to be at risk for harboring nodal metastases. The role of selective neck dissection continues to evolve: while initially designed as a staging and diagnostic procedure for patients without clinical evidence of nodal disease, a growing body of literature suggests that selective neck dissection has a therapeutic role in patients with clinical and histologic evidence of nodal metastases. The rationale behind selective neck dissection, its application in the clinically negative but histologically node-positive neck and the extended application of selective neck dissection in patients with clinical evidence of nodal disease are discussed.
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There has been a great deal of controversy regarding the appropriate method of management of oral cavity and oropharyngeal tumors that invade the mandible. The inability to acquire intraoperative bone margins can make the decision process complex. Preoperative imaging offers several advantages, however, there is no single modality that has proven accurate. Intraoperative assessment has been suggested as a method of evaluation, however, this approach does not allow for preoperative planning. The following is a review of the current literature regarding mandibular invasion and the indications for a marginal mandibulectomy.
Initial cancer evaluation includes assessment of histologic appearance, tumor grading, assessment of lymph node status, and presence of metastasis. However, traditional diagnostic methods such as histopathology and radiology are not sensitive enough to detect small numbers of cancer cells and are limited in their ability to predict response to treatment. Recently, there has been considerable progress in molecular diagnostics in these areas. Using molecular-based technologies, it is now possible to detect cancer early in asymptomatic individuals, identify minimal residual disease at histopathologic normal surgical margins, more precisely assess tumor burden in cancer patients, and more accurately assess the prognosis of the patients. Examples of these applications in the evaluation of head and neck cancer are reviewed here. However, despite the great promise of these new molecular approaches for cancer detection, much of the current technology limits their implementation into routine clinical use.
BACKGROUND: We aimed to identify patterns and predictors of second primary malignancy (SPM) of the aerodigestive tract (SPMADT) in patients with squamous cell carcinoma of the oral cavity (SCCOC) and larynx (SCCL). METHODS: One thousand two hundred fifty-seven patients from two existing databases were studied: 595 with SCCOC (1986-1995) and 662 with SCCL (1984-1998). The primary endpoint of interest was development of SPMADT, defined as a second primary neoplasm of the head and neck, esophagus, or lung. RESULTS: The 5-year SPMADT rate was 8% in the SCCL versus 10% in the SCCOC subgroup. Lung SPM was more common in the SCCL group; head and neck SPM was more common in the SCCOC group. Smokers had a fivefold increased risk, whereas alcohol use was associated with a twofold increased risk of SPMADT. CONCLUSIONS: The rates of SPMADT after treatment of SCCOC and SCCL are comparable, but the patterns are different. Smoking and alcohol use are independent predictors of SPMADT development.
BACKGROUND: We recently identified MUC1 as a target driving selection for 1q21 amplification and validated it as an independent marker of aggressive behavior in thyroid cancer (TC). The aims of this study were to determine whether TC cell lines retain MUC1 expression patterns that are seen in primary tumors, assess the role of MUC1 in tumor maintenance, and develop a virally delivered anti-MUC1 RNA interference (RNAi) that is effective in decreasing MUC1 expression in vitro. METHODS: Fifteen TC cell lines were screened for MUC1 protein expression. Cell lines with varying MUC1 protein levels were treated with anti-MUC1 monoclonal antibody to assess cell viability. A recombinant retroviral short hairpin RNAi delivery system against MUC1 was developed. Efficacy and optimal dosing of short hairpin RNA against MUC1 was determined. RESULTS: MUC1 expression patterns in TC cell lines were found to be similar to that seen in primary tumors. Treatment with anti-MUC1 antibody resulted in a significant decrease in cell viability in MUC1 over-expressing cell lines. MUC1-779 RNAi construct showed excellent infection efficiency and reproducible silencing. CONCLUSION: These data offer functional evidence that implicates MUC1 over-expression as a key molecular event in the pathogenesis of aggressive TC. Retrovirally delivered anti-MUC1 RNAi is effective in silencing MUC1 and merits further investigation to establish therapeutic efficacy and safety in anticipation of potential clinical application.
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Malignant melanomas are found in a variety of locations, ranging from sun-exposed skin to the nasal cavity and paranasal sinuses. Melanomas arising in the head and neck region comprise some 20% of all melanomas; of these, 7-15% occur in the vicinity of the external ear (most often on the helix). Auricular melanomas, like those arising elsewhere, are rare in childhood and are most often first diagnosed in men in their 50s. Melanomas of the external ear may present as flat pigmented lesions or as raised mass lesions; amelanotic (non-pigmented) variants exist as well. Auricular melanomas are frequently recognized pathologically as either superficial spreading melanomas or nodular melanomas. These tumors are aggressive, with a propensity for spreading to both regional lymph nodes and distant sites. Key pathologic prognostic features of auricular melanomas include the histological subtype, tumor thickness, level of invasion and presence of ulceration. Therapy includes both aggressive surgical attempts at excision in combination with sentinel node sampling in some instances and perhaps, adjuvant therapy as well. This is a tumor which is often overlooked until late in its course, with tragic consequences; vigilance and aggressive attempts at identifying these tumors at earlier stages are strongly advocated.
PURPOSE OF REVIEW: The purpose of this review is to summarize existing literature with respect to locally advanced thyroid cancer and define the intricacies of preoperative evaluation, surgical management of involved sites and postoperative treatment. RECENT FINDINGS: Locally invasive thyroid cancer is an uncommon disease process, which carries significant morbidity and mortality. Current treatment modalities include appropriate surgery, radioactive iodine treatment and external beam radiation therapy. Proper evaluation of the extent of disease, with complete gross tumor removal, is paramount in managing this difficult problem. Surgical treatment is still the mainstay for locally advanced thyroid cancer. SUMMARY: Little progress has been made in advancing the treatment of locally advanced thyroid cancer. Patient identification, evaluation and proper surgical management with adjuvant therapy, still remain the most effective course of treatment. Aggressive surgical treatment including removal of all gross tumor and still preserving vital structures along with adjuvant therapy is likely to offer the best results. There is a very high incidence of locoregional and distant failure in this group of patients. The understanding and recognition of histopathological variations, such as poorly differentiated thyroid cancer is also important. New molecular markers are needed to help identify and predict aggressive tumor behavior.
As life expectancy increases, surgeons can expect an increasing number of geriatric patients. In turn, the number of elderly patients presenting with head and neck cancer is likely to increase. Management of this subpopulation has become a source of debate because there is a paucity of randomized data regarding the effect of age on treatment response and morbidity associated with the treatment of head and neck cancer. The management of head and neck cancer in the elderly depends on the patient's age and general condition, the stage of disease, the effects of treatment on quality of life (such as speech and swallowing), patient and family wishes, and active physician participation in continued care. Elderly patient's comorbid conditions need appropriate attention especially if surgery is to be undertaken. The aim of this review is to examine the current literature in an attempt to develop an approach to the treatment of the elderly patient with head and neck cancer and to define the pertinent issues that require further study.
PURPOSE: The goal of this study was to identify chromosomal aberrations associated with poor outcome in patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: We assessed the global genomic composition of 82 HNSCCs from previously untreated patients with comparative genomic hybridization (CGH). The CGH data were subcategorized into individual cytogenetic bands. Only genomic aberrations occurring in more than 5% of cases were analyzed, and redundancies were eliminated. Each aberration was submitted to univariate analysis to assess its relationship with disease-specific survival (DSS). We used Monte Carlo simulations (MCS) to adjust P values for the log-rank approximate chi(2) statistics for each abnormality and further applied the Hochberg-Benjamini procedure to adjust the P values for multiple testing of the large number of abnormalities. We then submitted abnormalities whose univariate tests resulted in an adjusted P value of less than.15 together with significant demographic/clinical variables to stepwise Cox proportional hazards regression. We again verified and adjusted P values for the chi(2) approximation of the final model by MCS. RESULTS: CGH analysis revealed a recurrent pattern of chromosomal aberrations typical for HNSCC. Univariate analysis revealed 38 abnormalities that were correlated with DSS. After controlling for multiple comparisons and confounding effects of stage, five chromosomal aberrations were significantly associated with outcome, including amplification at 11q13, gain of 12q24, and losses at 5q11, 6q14, and 21q11 (MCS adjusted P =.0009 to P =.01). CONCLUSION: HNSCC contains a complex pattern of chromosomal aberrations. A sequential approach to control for multiple comparisons and effect of confounding variables allows the identification of clinically relevant aberrations. The significance of each individual abnormality merits further consideration.
Clinicopathological variables used at present for prognostication and treatment selection for papillary thyroid carcinomas (PTCs) do not uniformly predict tumor behavior, necessitating identification of novel prognostic markers. Complicating the assessment is the long natural history of PTC and our rudimentary knowledge of its genetic composition. In this study we took advantage of differences in clinical behavior of two distinct variants of PTC, the aggressive tall-cell variant (TCV) and indolent conventional PTC (cPTC), to identify molecular prognosticators of outcome using complementary genome wide analyses. Comparative genome hybridization (CGH) and cDNA microarray (17,840 genes) analyses were used to detect changes in DNA copy number and gene expression in pathological cPTC and TCV. The findings from CGH and cDNA microarray analyses were correlated and validated by real-time PCR and immunohistochemical analyses on a series of 100 cases of cPTC and TCV. Genes identified by this approach were evaluated as prognostic markers in cPTC by immunohistochemistry on tissue arrays. CGH identified significant differences in the presence (76 versus 27%; P = 0.001) and type of DNA copy number aberrations in TCV compared with cPTC. Recurrent gains of 1p34-36, 1q21, 6p21-22, 9q34, 11q13, 17q25, 19, and 22 and losses of 2q21-31, 4, 5p14-q21, 6q11-22, 8q11-22, 9q11-32, and 13q21-31 were unique to TCV. Hierarchical clustering of gene expression profiles revealed significant overlap between TCV and cPTC, but further analysis identified 82 dysregulated genes differentially expressed among the PTC variants. Of these, MUC1 was of particular interest because amplification of 1q by CGH correlated with MUC1 amplification by real-time PCR analysis and protein overexpression by immunohistochemistry in TCV (P = 0.005). Multivariate analysis revealed a significant association between MUC1 overexpression and treatment outcome, independent of histopathological categorization (P = 0.03). Analysis of a validation series containing a matched group of aggressive and indolent cPTCs confirmed the association between MUC1 overexpression and survival (relative risk, 2.3; 95% confidence interval, 1.1-5.5; P = 0.03). Our data suggest that MUC1 dysregulation is associated with aggressive behavior of PTC and may serve as a prognostic marker and potential therapeutic target in this disease.
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OBJECTIVE: To report the role of selective use of preoperative fine-needle aspiration biopsy (FNAB) in patients with major salivary gland lesions at a tertiary care cancer center. DESIGN: Retrospective review of FNAB results compared with final histologic diagnosis as the criterion standard. SETTING: An academic tertiary care cancer center. PATIENTS: A consecutive series of 258 patients who underwent FNAB of major salivary gland lesions between 1996 and 2000, of whom 169 had surgical resection. MAIN OUTCOME MEASURES: Predictive value, sensitivity, specificity, and accuracy. RESULTS: FNAB was performed in 169 (37%) of 463 salivary gland lesions undergoing surgical procedures. A total of 126 lesions were in the parotid gland and 44 in the submandibular gland. Seventy-nine lesions (46%) were malignant. There were 150 FNAB specimens (89%) that were satisfactory for evaluation. The FNAB diagnosis of malignant or suspicious lesion had positive and negative predictive values of 84% and 77%, respectively. Ten of 20 false-negative FNAB results were low-grade lymphoma on final histologic assessment. Fine-needle aspiration biopsy diagnosis of a benign neoplasm had positive and negative predictive values of 83% and 88%, respectively. A cytopathologic diagnosis of a nonneoplastic lesion was predictive in only 47% of cases. Fifteen (47%) of 32 lymphocyte-predominant FNAB specimens were lymphoma on final histologic assessment. Ten (20%) of 49 patients with history of a solid, non-head and neck malignancy had evidence of distant metastasis to the salivary gland by histologic and/or cytopathologic assessment. CONCLUSIONS: An FNAB diagnosis of malignant or neoplastic major salivary gland disease is generally predictive of final histologic diagnosis. The predictive value of a negative FNAB finding is low, and should not supersede clinical suspicion. Cytologic findings of a lymphocyte-predominant lesion should prompt further workup to rule out lymphoma.