K. Kelly Gallagher

Matted nodes: Poor prognostic marker in oropharyngeal squamous cell carcinoma independent of HPV and EGFR status

Despite better prognosis, there is a group of oropharyngeal squamous cell carcinoma (SCC) human papillomavirus (HPV)+ patients who experience treatment failure and succumb to distant metastasis.

Raman spectroscopy demonstrates Amifostine induced preservation of bone mineralization patterns in the irradiated murine mandible

PURPOSE Adjuvant radiotherapy in the management of head and neck cancer remains severely debilitating. Fortunately, newly developed agents aimed at decreasing radiation-induced damage have shown great promise. Amifostine (AMF) is a compound, which confers radio-protection to the exposed normal tissues, such as bone. Our intent is to utilize Raman spectroscopy to demonstrate how AMF preserves the mineral composition of the murine mandible following human equivalent radiation. METHODS Sprague Dawley rats were randomized into 3 experimental groups: control (n=5), XRT (n=5), and AMF-XRT (n=5). Both XRT and AMF groups underwent bioequivalent radiation of 70Gy in 5 fractions to the left hemimandible. AMF-XRT received Amifostine prior to radiation. Fifty-six days post-radiation, the hemimandibles were harvested, and Raman spectra were taken in the region of interest spanning 2mm behind the last molar. Bone mineral and matrix-specific Raman bands were analyzed using one-way ANOVA, with statistical significance at p<0.05. RESULTS The full-width at half-maximum of the primary phosphate band (FWHM) and the ratio of carbonate/phosphate intensities demonstrated significant differences between AMF-XRT versus XRT (p<0.01) and XRT versus control (p<0.01). There was no difference between AMF-XRT and control (p>0.05) in both Raman metrics. Computer-aided spectral subtraction further confirmed these results where AMF-XRT was spectrally similar to the control. Interestingly, the collagen cross-link ratio did not differ between XRT and AMF-XRT (p<0.01) but was significantly different from the control (p<0.01). CONCLUSION Our novel findings demonstrate that AMF prophylaxis maintains and protects bone mineral quality in the setting of radiation. Raman spectroscopy is an emerging and exceptionally attractive clinical translational technology to investigate and monitor both the destructive effects of radiation and the therapeutic remediation of AMF on the structural, physical and chemical qualities of bone.

Patterns of Nodal Metastasis and Prognosis in Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma

The current American Joint Committee on Cancer (AJCC) staging system may not accurately reflect survival in patients with human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (SCC). The purpose of this study was to develop a system that more precisely predicts survival.

Amifostine Remediates the Degenerative Effects of Radiation on the Mineralization Capacity of the Murine Mandible

Background: Radiotherapy, a cornerstone of head and neck cancer treatment, causes substantial morbidity to normal adjoining bone. The authors assessed the radioprotective effect of amifostine therapy on the mineralization of the mandible using micro–computed tomography. They hypothesized that amifostine would safeguard the mandible from radiation-induced disruption of the mineralization process and the associated failure of new bone creation. Methods: Male Sprague-Dawley rats were randomized into three groups: control (n = 8), radiation therapy (n = 5), and amifostine (n = 8). Animals in the radiation therapy and amifostine groups underwent human bioequivalent radiation of 70 Gy in five fractions to the left hemimandible. Fifty-six days after irradiation, the hemimandibles were harvested for radiomorphometric analyses. Results: Amifostine-treated animals exhibited less alopecia, mucositis, and weight loss in addition to increased cortical density in comparison with those treated with radiation therapy. Bone and tissue mineral densities showed statistically significant improvement in amifostine versus radiation therapy, and no difference was observed between amifostine and control groups. Detailed micro–computed tomographic analysis further demonstrated significant differences in the mineralization profile when comparing radiation therapy and amifostine. Amifostine maintained regions of lower mineralization consistent with the preservation of normal remodeling. Conclusions: The authors have successfully demonstrated the ability of amifostine pretreatment to protect the natural mineralization profile of bone. This reflects the capacity of amifostine prophylaxis to safeguard the normal surrounding mandible from the impediments of collateral damage imposed by irradiation. Further study can correlate these findings with the potential use of amifostine to prevent the devastating associated morbidities of radiotherapy such as pathologic fractures and osteoradionecrosis.

Matted nodes as a predictor of distant metastasis in advanced-stage III/IV oropharyngeal squamous cell carcinoma

We recently described the imaging characteristics of multiple confluent regional metastases (matted nodes) and found that this characteristic was associated with distant metastasis in patients with oropharyngeal squamous cell carcinoma (SCC). The purpose of this study was to determine if matted nodes are a predictive marker for distant metastasis.

Esthesioneuroblastoma: Updating Histologic Grading as It Relates to Prognosis

OBJECTIVE The Hyams grading system has been extensively used to predict prognosis in patients with esthesioneuroblastoma (ENB). However, most studies showing prognostic correlation group grading into I/II versus III/IV, essentially comparing low versus high grade. In addition, these studies include patients with variable treatment regimens, including some that were treated with chemoradiation alone. We aimed to determine whether additional histologic variables correlate with outcome with regard to disease free and overall survival in a series of patients universally treated with anterior skull base resection and +/- adjuvant chemoradiation. STUDY DESIGN A retrospective review of 27 patients with ENB was performed. METHODS The sections of tumor from these 27 patients were studied and reviewed with attention to percentage lobularity, degree of pleomorphism, degree of neurofibrillary matrix, and degree of apoptosis. In addition, the presence or absence of rosettes, necrosis, calcification, spindle cells, gland hyperplasia, and bone invasion were noted. Finally, the number of mitoses per high power field and the nature of chromatin (fine vs coarse) were recorded. The histopathologic features of these 27 ENBs were reviewed and correlated with clinical outcome. RESULTS There were 11 patients with recurrence (40.7% recurrence). There were 5 deaths (81.5% survival). The study cohorts mean overall survival was 158 months and the mean disease-free survival was 70.6 months. In terms of overall survival, necrosis and mitosis (#/10hpf) were significant but not when multivariate analysis was performed, these were not individually significant. In terms of disease-free survival, mitosis (#/10hpf) was significant but not on multivariate analysis. Gland hyperplasia was found to be a positive prognostic variable, associated with longer overall and disease-free survival, but only in combination with no spindle features and without necrosis. CONCLUSIONS An updated histologic grading system may provide more valuable prognostic information in patients with esthesioneuroblastoma treated with a standardized treatment paradigm.Objective: The Hyams grading system has been extensively used to predict prognosis in patients with esthesioneuroblastoma (ENB). However, most studies showing prognostic correlation group grading into I/II versus III/IV, essentially comparing low versus high grade. In addition, these studies include patients with variable treatment regimens, including some that were treated with chemoradiation alone. We aimed to determine whether additional histologic variables correlate with outcome with regard to disease free and overall survival in a series of patients universally treated with anterior skull base resection and +/– adjuvant chemoradiation. Study Design: A retrospective review of 27 patients with ENB was performed. Methods: The sections of tumor from these 27 patients were studied and reviewed with attention to percentage lobularity, degree of pleomorphism, degree of neurofibrillary matrix, and degree of apoptosis. In addition, the presence or absence of rosettes, necrosis, calcification, spindle cells, gland hyperplasia, and bone invasion were noted. Finally, the number of mitoses per high power field and the nature of chromatin (fine vs coarse) were recorded. The histopathologic features of these 27 ENBs were reviewed and correlated with clinical outcome. Results: There were 11 patients with recurrence (40.7% recurrence). There were 5 deaths (81.5% survival). The study cohort’s mean overall survival was 158 months and the mean disease-free survival was 70.6 months. In terms of overall survival, necrosis and mitosis (#/10hpf) were significant but not when multivariate analysis was performed, these were not individually significant. In terms of disease-free survival, mitosis (#/10hpf) was significant but not on multivariate analysis. Gland hyperplasia was found to be a positive prognostic variable, associated with longer overall and disease-free survival, but only in combination with no spindle features and without necrosis. Conclusions: An updated histologic grading system may provide more valuable prognostic information in patients with esthesioneuroblastoma treated with a standardized treatment paradigm.

Role of parathyroid hormone therapy in reversing radiation‐induced nonunion and normalization of radiomorphometrics in a murine mandibular model of distraction osteogenesis

The use of mandibular distraction osteogenesis (MDO) for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis has been described but, in fact, has seen limited clinical utility. Previous laboratory work has shown that radiation (XRT) causes decreased union formation, decreased cellularity, and decreased mineral density in an animal model of MDO. Our global hypothesis is that radiation‐induced bone damage is partly driven by the pathologic depletion of both the number and function of osteogenic cells. Parathyroid hormone (PTH) is a U.S. Food and Drug Administration–approved anabolic hormonal therapy that has demonstrated efficacy for increasing bone mineral density for the treatment of osteoporosis. We postulate that intermittent systemic administration of PTH will serve as an anabolic stimulant to cellular function that will act to reverse radiation‐induced damage and enhance bone regeneration in a murine mandibular model of DO.

Correlation of radiographic and pathologic findings of dermal lymphatic invasion in head and neck squamous cell carcinoma

SUMMARY: HNSCC that involves the skin is able to invade the dermal lymphatic system. Currently there is no way to identify patients with dermal lymphatic invasion preoperatively. The purpose of this study is to determine whether CT can predict dermal lymphatic invasion. Medical records, CT scans, and corresponding histopathologic slides were reviewed of HNSCC patients with skin resected as part of their treatment. Dermal lymphatic invasion was defined radiographically as linear reticulations of the dermis and subcutaneous fat adjacent to the tumor. Twelve patients were identified with imaging suggestive of dermal lymphatic invasion. The corresponding pathology slides showed only 1 of the 12 patients had dermal lymphatic invasion, whereas the other 11 specimens showed peritumoral inflammation without evidence of tumor invasion. This study demonstrates that the linear areas of reticulation are most commonly caused by peritumoral inflammation and are not due to dermal lymphatic invasion.

Correlation of Radiographic and Pathologic Findings of Dermal Lymphatic Invasion in Head and Neck Squamous Cell Carcinoma

SUMMARY: HNSCC that involves the skin is able to invade the dermal lymphatic system. Currently there is no way to identify patients with dermal lymphatic invasion preoperatively. The purpose of this study is to determine whether CT can predict dermal lymphatic invasion. Medical records, CT scans, and corresponding histopathologic slides were reviewed of HNSCC patients with skin resected as part of their treatment. Dermal lymphatic invasion was defined radiographically as linear reticulations of the dermis and subcutaneous fat adjacent to the tumor. Twelve patients were identified with imaging suggestive of dermal lymphatic invasion. The corresponding pathology slides showed only 1 of the 12 patients had dermal lymphatic invasion, whereas the other 11 specimens showed peritumoral inflammation without evidence of tumor invasion. This study demonstrates that the linear areas of reticulation are most commonly caused by peritumoral inflammation and are not due to dermal lymphatic invasion. ABBREVIATION: HNSCC head and neck squamous cell carcinoma