Outcomes of Head and Neck Microvascular Free Tissue Transfer for Advanced Cutaneous Squamous Cell Carcinoma: A Comparison of Solid Organ Transplant Recipients to Nontransplant Patients.

BACKGROUND: Patients with solid organ transplant (SOT) are at increased risk of developing aggressive cutaneous malignancies due to their immunosuppression, particularly cutaneous squamous cell carcinoma (cSCC). PURPOSE: There is limited data regarding SOT patients with locally advanced cSCC requiring radical surgery and microvascular free tissue transfer (MVFTT). Our objectives were to characterize outcomes in SOT patients and compare them with a non-SOT cohort. STUDY DESIGN: This is a retrospective cohort study of patients undergoing MVFTT for advanced cSCC of the head and neck between January 2016 and May 2020 at a tertiary referral center. Patients who underwent MVFTT as part of curative intent surgery for advanced cSCC during the study were considered for inclusion. Exclusion criteria included distant metastasis, palliative intent treatment, age less than 18 years, and lip primaries. PREDICTOR: The predictor variable was SOT status. A cohort of non-SOT patients was matched to the SOT cohort based on age, smoking status, tumor stage, and defect size. MAIN OUTCOME VARIABLES: The primary reconstructive outcome was the major surgical complications and secondary outcome measures included major medical complications and minor surgical complications. The primary oncologic outcome was overall survival and the secondary outcome was disease-specific survival. The primary predictor was transplant status. COVARIATES: Covariates included patient comorbidities, prior treatment, tumor stage, type of reconstruction, pathologic findings, and adjuvant therapy. ANALYSIS: Continuous and categorical variables were compared using Student's T test and Fisher's exact test. Survival was calculated using the Kaplan-Meier method and differences in survival between groups were calculated using the log-rank test. Statistical significance was set a priori at P ≤ .05. RESULTS: Fourteen SOT and 14 matched non-SOT patients met inclusion criteria. There was not a statistically significant difference in the rate of major surgical complications (7 vs 7%, P = .74) between the SOT and non-SOT cohorts. Rates of minor (21 vs 43%, P = .26) wound complications and medical complications (0 vs 14%, P = .24) were also similar between the SOT and non-SOT cohorts. Locoregional recurrences and distant metastasis were more common for SOT patients, though this was not statistically significant. Overall survival was significantly worse for SOT patients (21.7 vs 31.0 months, P = .04), though there was not a significant difference in disease-free survival (9.8 vs 31.0 months, P = .17). CONCLUSIONS AND RELEVANCE: MVFTT in the management of SOT patients with locally advanced head and neck cSCC demonstrates similar complication rates with non-SOT patients. While survival and oncologic outcomes are worse in the SOT cohort, aggressive surgical intervention with MVFTT can be performed with comparable complication rates to patients without a history of SOT.

Myeloid sarcoma of the skull base: A case report and systematic literature review.

Background: Myeloid sarcoma (MS), or chloroma, is a rare extramedullary malignant tumor that consists of undifferentiated granulocytic cells, and it is most commonly associated with acute myeloid leukemia (AML). Intracranial MS accounts for 0.4% of MS cases, and involvement of the skull base and visual dysfunction is rarely reported. However, the optimal treatment and response to treatment of skull base MS in the presence of visual symptoms is unknown. Case Description: A 30-year-old male with a history of AML presented with rapidly progressive vision loss and a sellar and parasellar mass with bilateral cavernous sinus and optic nerve encasement. The patient underwent endoscopic endonasal transsphenoidal biopsy revealing intracranial MS. He was treated postoperatively with high-dose intravenous and intrathecal cytarabine and had complete restoration of his vision by postoperative day 11. A systematic review of the literature identified six cases of skull base MS, five of whom presenting with visual symptoms. All patients underwent systemic chemotherapy with cytarabine and/or cyclophosphamide, with infrequent use of intrathecal chemotherapy or radiation. Those with reported visual outcomes were diagnosed 4 months or longer after symptom onset and demonstrated no visual improvement with treatment. Conclusion: Skull base MS is a rare disease entity with a high prevalence of visual dysfunction. Our patient's complete disappearance of intracranial disease and resolution of visual symptoms with systemic and intrathecal chemotherapy highlight the importance of timely diagnosis and appropriate treatment without a need for direct surgical decompression.

Effects of Preoperative Embolization on Juvenile Nasopharyngeal Angiofibroma Surgical Outcomes: A Study of the Kids' Inpatient Database.

Objectives The aim of the study is to evaluate the effect of preoperative vascular embolization (PVE) on juvenile nasopharyngeal angiofibroma (JNA) surgical outcomes using a national pediatric hospitalization database. Methods The health care cost and utilization project Kids' Inpatient Database was queried for all cases of operative management of JNA between the years of 1997 and 2016. Cases were stratified based on whether the patient received PVE. A multiple linear regression was used to predict the effect of PVE on hospital length of stay (LOS) and total cost while controlling for patient demographic factors and comorbidities. The odds ratio (OR) of receiving a perioperative blood transfusion was computed using a binary logistic regression for PVE patients. Results A total of 473 patients who underwent JNA surgical resection in this time period were identified. The use of PVE has increased from 0% in 1997 to 66% of all cases by 2016. PVE was found to decrease LOS by 1 day ( p = 0.036) and decrease the odds of needing a perioperative blood transfusion (OR = 0.511, p = 0.041). Patients receiving PVE were charged an additional $35,600 ( p < 0.001), but recent data in 2016 indicate that hospital costs for PVE are decreasing. Conclusion PVE of JNA is becoming increasingly prevalent. Embolization results in decreased hospital LOS and lower odds of needing blood transfusions. While embolization increases the cost of management, this trend should be re-evaluated as this procedure is becoming more widespread.

Racial and Socioeconomic Disparities in Patients With Meningioma: A Retrospective Cohort Study.

BACKGROUND: Meningiomas are the most common intracranial neoplasms. Although genomic analysis has helped elucidate differences in survival, there is evidence that racial disparities may influence outcomes. African Americans have a higher incidence of meningiomas and poorer survival outcomes. The etiology of these disparities remains unclear, but may include a combination of pathophysiology and other factors. OBJECTIVE: To determine factors that contribute to different clinical outcomes in racial populations. METHODS: We retrospectively reviewed 305 patients who underwent resection for meningiomas at a single tertiary care facility. We used descriptive statistics and univariate, multivariable, and Kaplan-Meier analyses to study clinical, radiographical, and histopathological differences. RESULTS: Minority patients were more likely to present through the emergency department than an outpatient clinic (P < .0001). They were more likely to present with more advanced clinical symptoms with lower Karnofsky Performance scores, more frequently had peritumoral edema (P = .0031), and experienced longer postoperative stays in the hospital (P = .0053), and African-American patients had higher hospitalization costs (P = .046) and were more likely to be publicly insured. Extent of resection was an independent predictor of recurrence freedom (P = .039). Presentation in clinic setting trended toward an association with recurrence-free survival (P = .055). We observed no significant difference in gross total resection rates, postoperative recurrence, or recurrence-free survival. CONCLUSION: Minority patients are more likely to present with severe symptoms, require longer perioperative hospitalization, and generate higher hospitalization costs. This may be due to socioeconomic factors that affect access to health care. Targeting barriers to access, especially to subspecialty care, may facilitate more appropriate and timely diagnosis, thereby improving patient care and outcomes.

Outcomes in Pediatric Transsphenoidal Pituitary Surgery Stratified by the Use of Image Guidance: An Analysis of the Kids' Inpatient Database from 1997 to 2016.

Background To evaluate the utilization of image guidance technology for pediatric transsphenoidal pituitary resection (TSPR) and analyze the complication rates, length of stay (LOS), and total cost for such surgeries as function of time and utilization of image guidance. Methods The Healthcare Cost and Utilization Project Kids' Inpatient Database (KID) was queried for all cases of TSPR between 1997 and 2016. Factors extracted included patient demographics, use of image guidance, LOS, total cost, and complications, including panhypopituitarism, diabetes insipidus (DI), cerebrospinal fluid (CSF) rhinorrhea, and cranial nerve (CN) III, IV, and VI palsies. Multivariate logistic regression was utilized to determine the odds ratio of developing panhypopituitarism, DI, CSF rhinorrhea, and CN palsies for image-guided versus nonimage-guided cases. A generalized linear model was used to determine the effect of image guidance on inflation-adjusted total cost and LOS. Results A total of 1,297 cases of TSPR were included in the KID over this time period. The majority were female, Caucasian, and older than 15 years. Utilization of image guidance has rapidly increased since 2006. Complication rates were comparable, but when controlling for other factors, the use of image guidance showed a lower risk of postoperative DI ( p = 0.05). The use of image guidance also resulted in a shorter LOS by 2.84 days ( p < 0.001) with no associated increase in total cost ( p = 0.663). Conclusion The use of imaging guidance for pediatric TSPR has precipitously increased in recent years, as it is cost-effective, decreases LOS, and may lead to lower complication rates, such as DI.

Endoscopic endonasal transsphenoidal direct access and Onyx embolization of a dural arteriovenous fistula mimicking a carotid-cavernous fistula: case report.

The classic presentation of a carotid-cavernous fistula (CCF) is unilateral painful proptosis, chemosis, and vision loss. Just as the goal of treatment for a dural arteriovenous fistula (dAVF) is obliteration of the entire fistulous connection and the proximal draining vein, the modern treatment of CCF is endovascular occlusion of the cavernous sinus via a transvenous or transarterial route. Here, the authors present the case of a woman with a paracavernous dAVF mimicking the clinical and radiographic presentation of a CCF. Without any endovascular route available to access the fistulous connection and venous drainage, the authors devised a novel direct hybrid approach by performing an endoscopic endonasal transsphenoidal direct puncture and Onyx embolization of the fistula.

Juvenile Nasopharyngeal Angiofibroma Outcomes and Cost: Analysis of the Kids' Inpatient Database.

OBJECTIVE: To report trends in Juvenile Nasopharyngeal Angiofibroma (JNA) hospitalizations and identify key factors affecting treatment outcomes and cost of care in JNA patients. METHODS: The Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database was queried for all cases of JNA between the years of 1997 and 2016. Key factors extracted were patient demographics, geographic region, hospital size, teaching status, elective admissions, and number of diagnoses and procedures performed during the hospitalization. These elements were correlated to length of stay (LOS) and cost-per-day (CPD) using a multiple linear regression (MLR). Regional variation in JNA diagnosis and changes in LOS and CPD trends over time were also analyzed. RESULTS: A total of 614 JNA patients were hospitalized in this time period, with a majority of patients identifying as male (98%) and Caucasian/White (55%). The average LOS has decreased by 0.14 day per year since 1997 (P = .0034) whereas the CPD has steadily increased by $2 380 per year (P < .001). MLR analysis revealed that while holding all other factors constant, patients who stayed at teaching hospitals had an increased LOS of 1.7 days (P = .026), but paid $11 961 less per day (P = .05). Regional variation in CPD was found in the Northeast region, where hospitalizations were more expensive by $9 801 per day compared to the South (P = .017). CONCLUSION: These results indicate hospital characteristics, such as teaching status and geographic region, may predict differences in JNA outcomes and cost. Healthcare providers should be cognizant of these variations to ensure optimal patient outcomes and expenditures.

Infundibular Epidermoid Cyst: Case Report and Systematic Review.

BACKGROUND: Intracranial epidermoid cysts are benign, congenital, keratinizing, squamous epithelial-lined cysts filled with keratin. They are uncommon and often pose a surgical challenge owing to the adherence to surrounding structures. They are typically found at the cerebellopontine angle or in the parasellar region, where they are associated with abnormal development of the Rathke pouch; involvement of the pituitary stalk is rare. CASE DESCRIPTION: The patient's electronic health record was queried for relevant data. A systematic review of the literature using dedicated search terms for cases of infundibular epidermoid cysts was conducted. We present a unique case of a 55-year-old male who presented with vision changes and was found to have a parasellar epidermoid cyst confined to the pituitary stalk. The patient underwent endoscopic transsphenoidal resection, and gross total resection was achieved. The patient's postoperative course was significant for possible chemical meningitis and the development of panhypopituitarism. The patient's vision subjectively improved after surgery. CONCLUSIONS: Although 3 other cases of epidermoid cysts involving the pituitary stalk were identified, our patient's tumor was unique in that it was confined to the stalk. Our patient's case highlights a surgical approach to parasellar epidermoid cysts and the possible complications associated therewith.

Chronic invasive fungal sinusitis causing a pathologic Le Fort I fracture in an immunocompetent patient.

We describe the case of a 77-year-old immunocompetent woman with a history of chronic rhinosinusitis who presented with a pathologic Le Fort I fracture after a forceful sneeze. Imaging revealed diffuse sinus opacification and a Le Fort type I complex fracture involving the maxilla, pterygoid plates, clivus, and right nasal bridge. The patient underwent endoscopic debridement of her sinuses, which revealed mucosal dehiscence and otherwise normal healthy bleeding tissue. Anatomic pathology identified necrotic bone with invasive fungal hyphae. Cultures demonstrated Burkholderia cepacia, diphtheroid organisms, and Enterococcus and Serratia spp. The patient was administered an intravenous antibiotic and antifungal for several months, but interval imaging found no significant improvement in bone healing although the stability of her palate had improved on clinical examination. Chronic rhinosinusitis has been found to be a complication of soft-tissue, orbital, and intracranial infections but, to the best of our knowledge, a pathologic facial fracture secondary to chronic invasive fungal and bacterial rhinosinusitis has not been previously reported in the literature.

Exploration for an Algorithm for Deintensification to Exclude the Retropharyngeal Site From Advanced Oropharyngeal Squamous Cell Carcinoma Treatment.

IMPORTANCE: Understanding the drainage patterns to the retropharyngeal lymph nodes is an important consideration in oropharyngeal squamous cell carcinoma (OPSCC) because treatment of these nodes is related to increased morbidity. Prediction of these drainage patterns could not only help minimize treatment morbidity but also prevent failures in at-risk patients as deintensification trials are under way for this disease. OBJECTIVE: To evaluate the prevalence of pathologic retropharyngeal adenopathy (RPA) in OPSCC relative to involvement of the oropharyngeal subsite, number of metastatic neck nodes, T classification, and N classification. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review from January 1, 2003, through December 31, 2010, at an academic referral center of 205 previously untreated patients with pathologically confirmed, advanced-stage (III, IV) OPSCC. Data analysis was performed from January 1, 2013, through June 30, 2015. EXPOSURE: Concurrent chemoradiotherapy. MAIN OUTCOMES AND MEASURES: Radiologic evidence of pathologic RPA was tabulated and related to involvement of the oropharyngeal subsite, number of metastatic neck nodes, T classification, and N classification. RESULTS: Of the 205 previously untreated patients (183 men; mean age, 56.1 years), pathologic RPA was identified in 37 (18.0%) of the 205 patients. Pathologic retropharyngeal lymph nodes were found in 12 (13.5%) of 89 patients with base of tongue cancers, 24 (22.0%) of 109 patients with tonsil cancers, and 1 (14.3%) of 7 patients with other oropharyngeal subsite cancers. Increasing prevalence of RPA was positively correlated with closer proximity to the posterior tonsillar pillar. A multivariable logistic regression model using the oropharyngeal subsite, involvement of the posterior tonsillar pillar, number of metastatic neck nodes, T classification, and N classification revealed that the number of metastatic neck nodes was statistically significant (odds ratio, 1.44; 95% CI, 1.20-1.71; P < .001). CONCLUSIONS AND RELEVANCE: The prevalence of pathologic RPA in this cohort was 18.0%, and patients with multiple nodes had the highest risk of pathologic RPA, followed by involvement of the posterior tonsillar pillar. However, these data suggest that there is no clear algorithm that can be used for deintensification to exclude the retropharyngeal site from the treatment volume using extent of disease gathered from pretreatment imaging for patients with advanced-stage OPSCC.

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

BACKGROUND: 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. METHODS: Radiologic lymph node characteristics on 205 patients with untreated stage III/IV with oropharyngeal SCC of whom 192 had known human papillomavirus (HPV) status underwent weekly carboplatin and paclitaxel with concomitant intensity-modulated radiation therapy (IMRT) between 2003 and 2010 with a minimum of 2-year of follow-up. RESULTS: The 3-year disease-specific survival (DSS) for patients with matted nodes was 58% versus 97% with nonmatted nodes (p = .0001). The prevalence of matted nodes in the population was 20%. The positive predictive value of matted nodes for distant metastasis was 66%, and the negative predictive value was 99%. CONCLUSION: Matted nodes are a predictive marker for distant disease and can be used for planning new clinical interventions.

Association Between Multimodality Neck Treatment and Work and Leisure Impairment: A Disease-Specific Measure to Assess Both Impairment and Rehabilitation After Neck Dissection.

IMPORTANCE: This study describes the effect of adjuvant treatment on shoulder-related quality of life, leisure activities, and employment for patients undergoing neck dissection for head and neck cancer. OBJECTIVE: To explore the association between treatment outcome and shoulder-related on critical daily life functions such as employment and recreation. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of patients with head and neck cancer at a tertiary care hospital. EXPOSURES: Level V­sparing selective neck dissection or modified radical neck dissection sparing the accessory nerve, with or without radiation therapy and/or chemotherapy. MAIN OUTCOMES AND MEASURES: Patients completed the Neck Dissection Impairment Index (NDII), with scores ranging from 0 to 100 and higher scores indicating better shoulder functioning and shoulder-related quality of life, and underwent objective testing with the Constant-Murley Shoulder Function Test (Constant test) at least 12 months after the completion of all adjuvant treatment. Additional outcome measures related to physical therapy, pain medication use, leisure activity, and employment status. RESULTS: We evaluated 167 patients who underwent 121 selective neck dissections and 46 modified radical neck dissections. The median (range) NDII score was 90 (10-100). Patients with modified radical neck dissection reported lower scores than those with selective neck dissection (85 [10-100] vs. 92 [30-100]; P = .01). Multivariable analysis showed that advanced-stage disease (mean, 77 [range, 25-100] vs. 87 [18-100]; P = .006), radiation therapy (80 [10-100] vs. 88 [50-100]; P = .03), and chemotherapy (77 [30-100] vs. 83 [18-100]; P = .002) were associated with greater shoulder impairment. The NDII and Constant test were well correlated (0.64; P < .001). Change in leisure activity was correlated with greater impairment (median [range] NDII score, 90 [18-100] for patients with no change vs. 53 [10-100] for patients with change, P = .005; Constant score, 85 [12-100] vs. 68 [10-88], P = .004). Patients who remained employed or resumed working had higher median (range) NDII scores (94 [10-100] and 88 [75-100], respectively) than those who limited or stopped working (70 [10-100]), which also correlates with greater shoulder impairment (P < .001). CONCLUSIONS AND RELEVANCE: More aggressive treatment, either in the form of increased surgical dissection, radiation therapy, or chemotherapy, was associated with worse shoulder function and quality of life. The degree of impairment perceived by the patient and measured in objective testing was correlated with leisure activity and employment status. These findings may stimulate further investigation related to optimizing quality of life following neck dissection.

Patterns of nodal metastasis and prognosis in human papillomavirus-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: 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. METHODS: CT scans from 156 patients who underwent chemoradiation for advanced-stage oropharyngeal SCC with >2 years follow-up were reviewed. We modeled patterns of nodal metastasis associated with different survival rates. We defined HPV+ N1 as a single node <6 cm, ipsilaterally, contralaterally, or bilaterally. HPV+ N2 was defined as a single node ≥6 cm or ≥2 nodes ipsilaterally/contralaterally or ≥3 nodes bilaterally. HPV+ N3 was defined as matted nodes. RESULTS: There was no significant difference in disease-specific survival (DSS; p = .14) or overall survival (OS; p = .16) by AJCC classification. In patients grouped by HPV+ N1, HPV+ N2, and HPV+ N3 nodal classification, significant differences in DSS (100%, 92%, and 55%, respectively; p = .0001) and OS (100%, 96%, and 55%, respectively; p = .0001) were found. CONCLUSION: A staging system with reclassification of size, bilaterality, and matted nodes more accurately reflects survival differences in this cohort of patients. Review of the AJCC staging system with these criteria should be considered for HPV-positive oropharyngeal SCC.

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

BACKGROUND: 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. METHODS: A total of 20 isogenic male Lewis rats were randomly assigned into 3 groups. Group 1 (XRT-DO, n = 7) and group 2 (XRT-DO-PTH, n = 5) received a human bioequivalent dose of 70 Gy fractionated over 5 days. All groups including group 3 (DO, n = 8) underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Four days later, mandibular DO was performed at a rate of 0.3 mm every 12 hours to reach a maximum gap of 5.1 mm. Group 2 was injected PTH (60 µg/kg) subcutaneously daily for 3 weeks following the start of MDO. On postoperative day 41, all left hemimandibles were harvested. Micro-CT at 45-µm voxel size was performed and radiomorphometrics parameters of bone mineralization were generated. Union quality was evaluated on a 4-point qualitative grading scale. Radiomorphometric data were analyzed using 1-way ANOVA, and union quality assessment was analyzed via the Mann-Whitney test. Statistical significance was considered at p ≤ .05. RESULTS: Groups 1 and 2 appropriately demonstrated clinical signs of radiation-induced stress ranging from alopecia to mucositis. Union quality was significantly higher in PTH-treated XRT-DO animals, compared with XRT-DO group animals (p = .02). Mineralization metrics, including bone volume fraction (BVF) and bone mineral density (BMD), also showed statistically significant improvement. The groups that were treated with PTH showed no statistical differences in union or radiomorphometrics when compared with DO in nonradiated animals. CONCLUSION: We have successfully demonstrated the therapeutic efficacy of PTH to stimulate and enhance bone regeneration in our irradiated murine mandibular model of DO. Our investigation effectively resulted in statistically significant increases in BMD, BVF, and clinical unions in PTH-treated mandibles. PTH demonstrates immense potential to treat clinical pathologies where remediation of bone regeneration is essential.

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.

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: poor prognostic marker in oropharyngeal squamous cell carcinoma independent of HPV and EGFR status.

BACKGROUND: 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. METHODS: Seventy-eight previously untreated patients nested in a concurrent chemoradiation protocol were reviewed to correlate patterns of local-regional tumor extent to distant metastasis. Biomarker assessment was: HPV in situ hybridization and epidermal growth factor receptor (EGFR) immunointensity. RESULTS: The 3-year disease-specific survival (DSS) for patients presenting with and without matted nodes was 69% and 94%, respectively (p = .003). Matted nodes were a poor prognostic factor independent of T classification, HPV, EGFR, and smoking status. For patients who were HPV+, 7 of 11 died of distant metastasis and 6 of 7 with distant metastasis had matted nodes. CONCLUSION: Matted nodes are a novel marker of poor prognosis in oropharyngeal SCC independent of established prognostic factors. Matted nodes may identify patients at risk for the development of distant metastasis who could benefit from systemic therapy, whereas patients without matted nodes may be candidates for de-escalation of therapy.