Citations

Background: Historical outcomes in anaplastic thyroid carcinoma (ATC) are poor, with a median survival of only 5 months and <20% of patients surviving 1 year from diagnosis. We hypothesized that survival in newly diagnosed patients with stages IVA and IVB locoregionally confined ATC might be improved by utilizing an aggressive therapeutic approach, prioritizing both the eradication of disease in the neck and preemptive treatment of occult metastatic disease. Methods: Between January 1, 2003, and December 31, 2007, 25 new ATC patients were evaluated at our institution. Of these 25 patients, 10 (40%) had metastatic disease at diagnosis and therefore underwent palliative treatment, whereas 5 (20%) had regionally confined disease and desired treatment at their local medical facilities. The remaining 10 consecutive patients (40%) had regionally confined ATC and elected aggressive therapy combining individualized surgery (where feasible), intensity-modulated radiation therapy (IMRT), and radiosensitizing + adjuvant chemotherapy intending four cycles of docetaxel + doxorubicin. Outcomes were assessed on an intention to treat basis. Results: There were no deaths from therapy, but hospitalization was required in two patients (20%) because of treatment-related adverse events. Five patients (50%) are alive and cancer-free, all having been followed >32 months (range: 32–89 months; median: 44 months) with a median overall Kaplan–Meier survival of 60 months. Overall survival at 1 and 2 years was 70% and 60%, respectively, compared to <20% historical survival at 1 year in analogous patients previously treated with surgery and conventional postoperative radiation at our and other institutions. Conclusions: Although based upon a small series of consecutively treated patients, an aggressive approach combining IMRT and radiosensitizing plus adjuvant chemotherapy appears to improve outcomes, including survival in stages IVA and IVB regionally confined ATC, but remains of uncertain benefit in patients with stage IVC (metastatic) disease. Also uncertain is the optimal chemotherapy regimen to use in conjunction with IMRT. Further multicenter randomized trials are required to define optimal therapy in this rare but deadly cancer.

Speech-language pathologists (SLPs) in the general medical hospital setting spend approximately half of their time providing swallowing services. Other professions, including occupational therapists (OTs) and dietitians, promote themselves as disciplines well suited to assist patients with dysphagia. Responses to a survey distributed by the American Speech-Language-Hearing-Association (ASHA) in 2007 indicated that 83% of SLPs working in hospitals believed encroachment and defining professional boundaries was a problem. The highest level of personal experience with encroachment was with occupational therapy. Effective 2009, the American Occupational Therapy Association (AOTA) began offering Specialty Certification in Feeding, Eating and Swallowing (SCFES) to OTs and OTAs who meet specific educational and clinical experience requirements. This article reviews the many reasons why SLPs are the professionals best suited for assisting patients with swallowing disorders. It provides specific strategies to assist SLPs in promoting our discipline as the providers of dysphagia services.

AbstractVorinostat, an oral histone deacetylase inhibitor with antitumor activity, is in clinical trials for hematologic and solid tumors that metastasize and compromise bone structure. Consequently, there is a requirement to establish the effects of vorinostat on tumor growth within bone. Breast (MDA-231) and prostate (PC3) cancer cells were injected into tibias of SCID/NCr mice and the effects of vorinostat on tumor growth and osteolytic disease were assessed by radiography, micro-computed tomography, and histologic and molecular analyses. Vorinostat-treated and control mice without tumors were also examined. Tumor growth in bone was reduced ∼33% by vorinostat with inhibited osteolysis in the first few weeks of the experiment. However, osteolysis became more severe in both the vehicle and vorinostat-treated groups. Vorinostat increased the expression of tumor-derived factors promoting bone resorption, including PTHrP, IL-8, and osteopontin. After 4 weeks of vorinostat therapy, the non–tumor-bearing contralateral femurs and limbs from vorinostat-treated tumor-free SCID mice showed significant bone loss (50% volume density of controls). Thus, our studies indicate that vorinostat effectively inhibits tumor growth in bone, but has a negative systemic effect reducing normal trabecular bone mass. Vorinostat treatment reduces tumor growth in bone and accompanying osteolytic disease as a result of decreased tumor burden in bone. However, vorinostat can promote osteopenia throughout the skeleton independent of tumor cell activity. Mol Cancer Ther; 9(12); 3210–20. ©2010 AACR.

Collateral circulation in intracranial atherosclerosis has never been systematically characterized. We investigated collaterals in a multicenter trial of symptomatic intracranial atherosclerotic disease. Baseline angiography was reviewed for information on collaterals in stenoses of the internal carotid, middle cerebral, vertebral, and basilar arteries. A battery of angiographic scales was utilized to evaluate lesion site, arterial patency, antegrade flow, downstream territorial perfusion, and collateral circulation, blinded to all other data. Collateral circulation was adequately available for analysis in 287/569 (50%) subjects with proximal arterial stenoses ranging from 50% to 99%. Extent of collaterals was absent or none in 69%, slow or minimal in 10%, more rapid, yet incomplete perfusion of territory in 7%, complete but delayed perfusion in 11%, and rapid, complete collateral perfusion in 4%. Extent of collateral flow correlated with percentage of stenosis ( P < 0.0001), with more severe stenoses exhibiting greater compensation via collaterals. Overall, collateral grade increased with diminished antegrade flow across the lesion (thrombolysis in myocardial ischemia) and resultant downstream perfusion (thrombolysis in cerebral infarction) (both P<0.001). Our findings provide the initial detailed description of collaterals across a variety of stenoses, suggesting that collateral perfusion is a pivotal component in pathophysiology of intracranial atherosclerosis and implicating the need for further evaluation in ongoing studies.