Snehal G. Patel

Primary mucosal malignant melanoma of the head and neck

The relative rarity of mucosal melanomas of the head and neck (MMHN) has made analysis of treatment approaches difficult. Advances in diagnostic techniques and treatment interventions have had obvious impact on outcomes in cutaneous melanoma, but the effects on outcome in MMHN remain undefined. This study aims to assess the outcome and identify clinical and histologic prognostic indicators in a recent cohort of patients with MMHN treated at a single institution.

Diagnostic and Prognostic Value of [18F]Fluorodeoxyglucose Positron Emission Tomography for Recurrent Head and Neck Squamous Cell Carcinoma

PURPOSE: Patients with recurrent head and neck squamous cell carcinoma (HNSCC) present a diagnostic and therapeutic challenge. We evaluated the diagnostic accuracy and prognostic value of [18F]fluorodeoxyglucose positron emission tomography (PET) in this patient population. PATIENTS AND METHODS: We performed a retrospective review of 143 patients with previously treated HNSCC who underwent 181 PET scans at our institution from May 1996 through April 2001 to detect recurrent disease. Disease recurrence within 6 months was used as the gold standard for assessing true disease status at PET. RESULTS: With equivocal sites considered positive, the sensitivity and specificity of PET for detecting recurrence overall were 96% and 72%, respectively. PET was highly sensitive and specific at regional and distant sites. At local sites, sensitivity was high, but specificity was lower because of false-positive findings. One fifth of all false-positive PET scans occurred at sites of known inflammation or infection. The a...

TNM Staging of Cancers of the Head and Neck: Striving for Uniformity Among Diversity†

The sixth edition of the tumor‐node‐metastasis staging system for head and neck cancers incorporates some significant shifts in philosophy. As treatment paradigms shift and data from ongoing clinical and basic research become available, further revisions may be expected in the future. The purpose of this review is to highlight the complexities involved in developing a user‐friendly staging system and to report the major changes in the new version. The authors also discuss some areas of current interest that may have the potential to lead to future modifications.

COMPLICATIONS OF CRANIOFACIAL RESECTION FOR MALIGNANT TUMORS OF THE SKULL BASE: REPORT OF AN INTERNATIONAL COLLABORATIVE STUDY

Advances in imaging, surgical technique, and perioperative care have made craniofacial resection (CFR) an effective and safe option for treating malignant tumors involving the skull base. The procedure does, however, have complications. Because of the relative rarity of these tumors, most existing data on postoperative complications come from individual reports of relatively small series of patients. This international collaborative report examines a large cohort of patients accumulated from multiple institutions with the aim of identifying patient‐related and tumor‐related predictors of postoperative morbidity and mortality and set a benchmark for future studies.

Clinical Utility of 18F-FDG PET/CT in Assessing the Neck After Concurrent Chemoradiotherapy for Locoregional Advanced Head and Neck Cancer

For patients with locoregional advanced head and neck squamous cell carcinoma (HNSCC), concurrent chemoradiotherapy is a widely accepted treatment, but the need for subsequent neck dissection remains controversial. We investigated the clinical utility of 18F-FDG PET/CT in this setting. Methods: In this Institutional Review Board (IRB)–approved and Health Insurance Portability and Accountability Act (HIPPA)–compliant retrospective study, we reviewed the records of patients with HNSCC who were treated by concurrent chemoradiation therapy between March 2002 and December 2004. Patients with lymph node metastases who underwent 18F-FDG PET/CT ≥ 8 wk after the end of therapy were included. 18F-FDG PET/CT findings were validated by biopsy, histopathology of neck dissection specimens (n = 18), or clinical and imaging follow-up (median, 37 mo). Results: Sixty-five patients with a total of 84 heminecks could be evaluated. 18F-FDG PET/CT (visual analysis) detected residual nodal disease with a sensitivity of 71%, a specificity of 89%, a positive predictive value (PPV) of 38%, a negative predictive value (NPV) of 97%, and an accuracy of 88%. Twenty-nine heminecks contained residual enlarged lymph nodes (diameter, ≥1.0 cm), but viable tumor was found in only 5 of them. 18F-FDG PET/CT was true-positive in 4 and false-positive in 6 heminecks, but the NPV was high at 94%. Fifty-five heminecks contained no residual enlarged nodes, and PET/CT was true-negative in 50 of these, yielding a specificity of 96% and an NPV of 98%. Lack of residual lymphadenopathy on CT had an NPV of 96%. Finally, normal 18F-FDG PET/CT excluded residual disease at the primary site with a specificity of 95%, an NPV of 97%, and an accuracy of 92%. Conclusion: In patients with HNSCC, normal 18F-FDG PET/CT after chemoradiotherapy has a high NPV and specificity for excluding residual locoregional disease. In patients without residual lymphadenopathy, neck dissection may be withheld safely. In patients with residual lymphadenopathy, a lack of abnormal 18F-FDG uptake in these nodes also excludes viable tumor with high certainty, but confirmation of these data in a prospective study may be necessary before negative 18F-FDG PET/CT may become the only, or at least most-decisive, criterion in the management of the neck after chemoradiotherapy.

Craniofacial resection for malignant paranasal sinus tumors: Report of an international collaborative study

Malignant tumors of the superior sinonasal vault are rare, and, because of this and the varied histologic findings, most outcomes data reflect the experience of small patient cohorts. This International Collaborative study examines a large cohort of patients accumulated from multiple institutions experienced in craniofacial surgery, with the aim of reporting benchmark figures for outcomes and identifying patient‐related and tumor‐related predictors of prognosis after craniofacial resection (CFR).

Second Primary Cancers After an Index Head and Neck Cancer: Subsite-Specific Trends in the Era of Human Papillomavirus–Associated Oropharyngeal Cancer

PURPOSE Patients with head and neck squamous cell carcinoma (HNSCC) are at elevated risk of second primary malignancies (SPM), most commonly of the head and neck (HN), lung, and esophagus. Our objectives were to identify HNSCC subsite-specific differences in SPM risk and distribution and to describe trends in risk over 3 decades, before and during the era of human papillomavirus (HPV) -associated oropharyngeal SCC. METHODS Population-based cohort study of 75,087 patients with HNSCC in the Surveillance, Epidemiology, and End Results (SEER) program. SPM risk was quantified by using standardized incidence ratios (SIRs), excess absolute risk (EAR) per 10,000 person-years at risk (PYR), and number needed to observe. Trends in SPM risk were analyzed by using joinpoint log-linear regression. RESULTS In patients with HNSCC, the SIR of second primary solid tumor was 2.2 (95% CI, 2.1 to 2.2), and the EAR was 167.7 cancers per 10,000 PYR. The risk of SPM was highest for hypopharyngeal SCC (SIR, 3.5; EAR, 307.1 per 10,000 PYR) and lowest for laryngeal SCC (SIR, 1.9; EAR, 147.8 per 10,000 PYR). The most common SPM site for patients with oral cavity and oropharynx SCC was HN; for patients with laryngeal and hypopharyngeal cancer, it was the lung. Since 1991, SPM risk has decreased significantly among patients with oropharyngeal SCC (annual percentage change in EAR, -4.6%; P = .03). CONCLUSION In patients with HNSCC, the risk and distribution of SPM differ significantly according to subsite of the index cancer. Before the 1990s, hypopharynx and oropharynx cancers carried the highest excess risk of SPM. Since then, during the HPV era, SPM risk associated with oropharyngeal SCC has declined to the lowest risk level of any subsite.

Genome-wide appraisal of thyroid cancer progression.

Several lines of evidence suggest that follicular cell-derived thyroid cancers represent a continuum of disease that progresses from the highly curable well-differentiated thyroid cancers to the universally fatal anaplastic cancers. However, the genetic mechanisms underlying thyroid cancer progression remain ill defined. We compared the molecular-cytogenetic profiles derived from comparative genomic hybridization (CGH) analysis of major histological variants of thyroid cancer to define genetic variables associated with progression. Overall, a sequential increase in chromosomal complexity was observed from well-differentiated papillary thyroid cancer to poorly differentiated and anaplastic carcinomas, both in terms of the presence of CGH detectable abnormalities (P = 0.003) and the median number of abnormalities per case (P < 0.001). The presence of multiple abnormalities common to all thyroid cancer variants, including gains of 5p15, 5q11-13, 19p, and 19q and loss of 8p, suggests that these tumors are derived from a common genetic pathway. Gains of 1p34-36, 6p21, 9q34, 17q25, and 20q and losses of 1p11-p31, 2q32-33, 4q11-13, 6q21, and 13q21-31 may represent secondary events in progression, as they were only detected in poorly differentiated and anaplastic carcinomas. Finally, recurrent gains at 3p13-14 and 11q13, and loss of 5q11-31 were unique to anaplastic carcinomas, suggesting they may be markers for anaplastic transformation. Our data suggests that the development of chromosomal instability underlies the progression to more aggressive phenotypes of thyroid cancer and sheds light on the possible genomic aberrations that may be selected for during this process.

Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual.

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Genome-wide profiling of papillary thyroid cancer identifies MUC1 as an independent prognostic marker.

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.