Dennis H. Kraus

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...

Concurrent Cetuximab, Cisplatin, and Concomitant Boost Radiotherapy for Locoregionally Advanced, Squamous Cell Head and Neck Cancer: A Pilot Phase II Study of a New Combined-Modality Paradigm

PURPOSE Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor. Cetuximab has activity in squamous cell carcinoma and enhances both chemotherapy and radiotherapy. We conducted a pilot phase II study of a new combined-modality paradigm of targeted therapy (cetuximab) with chemoradiotherapy. PATIENTS AND METHODS Eligible patients had stage III or IV, M0, squamous cell head and neck cancer. Treatment included concomitant boost radiotherapy (1.8 Gy/d weeks 1 to 6; boost: 1.6 Gy 4 to 6 hours later weeks 5 to 6; 70 Gy total to gross disease), cisplatin (100 mg/m2 intravenously weeks 1 and 4), and cetuximab (400 mg/m2 intravenously week 1, followed by 250 mg/m2 weeks 2 to 10). RESULTS Twenty-two patients were enrolled (median age, 57 years; range, 41 to 72 years; median Karnofsky status, 90%; range, 70% to 90%; oropharynx primary tumor, 59% of patients; T4, 36%; N2/3, 77%; stage IV disease, 86%). One patient did not receive study treatment because of an ineligible diagnosis. The severity of expected, acute toxicities was typical of concurrent cisplatin and radiotherapy alone. Grade 3 or 4 cetuximab-related toxicities included acne-like rash (10%) and hypersensitivity (5%). However, the study was closed for significant adverse events, including two deaths (one pneumonia and one unknown cause), one myocardial infarction, one bacteremia, and one atrial fibrillation. With a median follow-up of 52 months, the 3-year overall survival rate is 76%, the 3-year progression-free survival rate is 56%, and the 3-year locoregional control rate is 71%. CONCLUSION This regimen is not currently recommended outside of the clinical trial setting. Further investigation of its safety profile is needed. However, preliminary efficacy is encouraging, and further development of this targeted combined-modality paradigm is warranted.

Detailed quality of life assessment in patients treated with primary radiotherapy for squamous cell cancer of the base of the tongue

This study was conducted to evaluate quality of life in patients treated with primary radiotherapy (RT) for cancer of the base of tongue.

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.

Prospective functional voice assessment in patients undergoing thyroid surgery.

ObjectiveTo analyze voice function before and after thyroidectomy for patients with normal preoperative voice using a standardized multidimensional voice assessment protocol. Summary Background DataThe natural history of post-thyroidectomy voice disturbances for patients with preserved laryngeal nerve function has not been systematically studied and characterized with the intent of using the data for postoperative voice rehabilitation. MethodsDuring a prospective single-arm study, patients with normal voice underwent functional voice testing using a standardized voice grading scale and a battery of acoustic, aerodynamic, glottographic, and videostroboscopic tests before, 1 week after, and 3 months after thyroidectomy. Differences in observed sample means were evaluated using analysis of covariance or t test; categorical data was analyzed using the Fisher exact or chi-square test. ResultsFifty-four patients were enrolled; 50 and 46 were evaluable at 1 week and 3 months, respectively. No patient developed recurrent laryngeal nerve injury; one had superior laryngeal nerve injury. Fifteen (30%) patients reported early subjective voice change and seven (14%) reported late (3-month) subjective voice change. Forty-two (84%) patients had significant objective change in at least one voice parameter. Six (12%) had significant alterations in more than three voice measures, of which four (67%) were symptomatic, whereas 25% with three or fewer objective changes had symptoms. Patients with persistent voice change at 3 months had an increased likelihood of multiple (more than three) early objective changes (43% vs. 7%). Early maximum phonational frequency range and vocal jitter changes from baseline were significantly associated with voice symptoms at 3 months. ConclusionsEarly vocal symptoms are common following thyroidectomy and persist in 14% of patients. Multiple (more than three) objective voice changes correlate with early and late postoperative symptoms. Alterations in maximum phonational frequency range and vocal jitter predict late perceived vocal changes. Factors other than laryngeal nerve injury appear to alter post-thyroidectomy voice. The variability of patient symptoms underscores the importance of understanding the physiology of dysphonia.

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).

PET Monitoring of Therapy Response in Head and Neck Squamous Cell Carcinoma

In the Western world, more than 90% of head and neck cancers are head and neck squamous cell carcinomas (HNSCCs). The most appropriate treatment approach for HNSCC varies with the disease stage and disease site in the head and neck. Concurrent chemoradiotherapy has become a widely used means for the definitive treatment of locoregionally advanced HNSCC. Although this multimodality treatment provides higher response rates than radiotherapy alone, the detection of residual viable tumor after the end of therapy remains an important issue and is one of the major applications of 18F-FDG PET. Studies have shown that negative 18F-FDG PET or PET/CT results after concurrent chemoradiotherapy have a high negative predictive value (>95%), whereas the positive predictive value is only about 50%. However, when applied properly, FDG PET/CT can exclude residual disease in most patients, particularly patients with residual enlarged lymph nodes who would otherwise undergo neck dissection. In contrast to other malignancies, data are limited on the utility of 18F-FDG PET for monitoring the response to induction chemotherapy in HNSCC or for assessing treatment response early during the course of definitive chemoradiotherapy. The proliferation marker 18F-3′-deoxy-3′fluorothymidine is currently under study for this purpose. Beyond standard chemotherapy, newer treatment regimens in HNSCC take advantage of our improved understanding of tumor biology. Two molecules important in the progression of HNSCC are the epidermal growth factor receptor and the vascular endothelial growth factor (VEGF) and its receptor VEGF-R. Drugs attacking these molecules are now under study for HNSCC. PET probes have been developed for imaging the presence of these molecules in HNSCC and their inhibition by specific drug interaction; the relevance of these probes for response assessment in HNSCC will be discussed. Hypoxia is a common phenomenon in HNSCC and renders cancers resistant to chemo- and radiotherapy. Imaging and quantification of hypoxia with PET probes is under study and may become a prerequisite for overcoming chemo- and radioresistance using radiosensitizing drugs or hypoxia-directed irradiation techniques and for monitoring the response to these techniques in selected groups of patients. Although 18F-FDG PET/CT will remain the major clinical tool for monitoring treatment in HNSCC, other PET probes may have a role in identifying patients who are likely to benefit from treatment strategies that include biologic agents such as epidermal growth factor receptor inhibitors or VEGF inhibitors.

Sensorineural hearing loss in combined modality treatment of nasopharyngeal carcinoma.

Combined modality therapy has become the standard of care for nasopharyngeal carcinoma, yet the combined ototoxic effects of radiation and cisplatin are poorly understood. The incidence and severity of sensorineural hearing loss (SNHL) with combined modality therapy was evaluated and the dose–response relation between radiation and hearing loss was investigated.