Robert L. Foote

Enhanced Survival in Locoregionally Confined Anaplastic Thyroid Carcinoma: A Single-Institution Experience Using Aggressive Multimodal Therapy

BACKGROUNDnHistorical 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.nnnMETHODSnBetween 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 radiosensitizingu2009+u2009adjuvant chemotherapy intending four cycles of docetaxelu2009+u2009doxorubicin. Outcomes were assessed on an intention to treat basis.nnnRESULTSnThere 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.nnnCONCLUSIONSnAlthough 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.

Is interstitial implantation essential for successful radiotherapeutic treatment of base of tongue carcinoma

The role of interstitial implantation in the radiotherapeutic treatment of base of tongue carcinoma remains controversial. At the University of Florida, essentially all patients with base of tongue cancer have been managed initially by radiation therapy (with or without neck dissection) with operation reserved for radiation therapy failure. Eighty-four patients with invasive squamous cell carcinoma of the base of the tongue were treated with continuous-course external-beam irradiation without interstitial implantation between October 1964 and July 1986. Treatment was administered once-a-day in 59 patients and twice-a-day in 25 patients. The median follow-up was 99 months (range, 25-284 months). No patient was lost to follow-up. Local failure occurred in 1/9 patients (11%) with T1 lesions, 3/30 (10%) with T2, 6/31 (19%) with T3, and 9/14 (64%) with T4. If one excludes from the local control analysis those patients who died of intercurrent or metastatic disease within 2 years with their primary tumor continuously controlled, then the rates of local control are as follows: T1, 3/4; T2, 22/25 (88%); T3, 20/26 (77%); T4, 5/14 (36%). An improved local control rate for T4 tumors was noted with twice-a-day fractionation. Eighty-eight percent of N0-N1 necks and 79% of N2-N3 necks were treated successfully by irradiation with or without planned neck dissection. Five-year rates of continuous disease control above the clavicles were as follows: Stage I-II, 100%; Stage III, 72%; Stage IVA, 78%; Stage IVB, 44%. Five-year absolute and relapse-free survival rates for the entire group were 43% and 58%, respectively. The incidence of bone exposure was 6%, and that of soft-tissue necrosis was 19%. In all but one case, the complication was mild to moderate in severity and healed with conservative management. These results compare favorably with those recently published in the literature supporting moderate-dose external-beam irradiation combined with interstitial implantation. We conclude that interstitial implantation is not essential for the successful radiotherapeutic treatment of base of tongue carcinoma.

Results of repeated gamma knife radiosurgery for medically unresponsive trigeminal neuralgia

The purpose of this paper was to note a potential source of error in magnetic resonance (MR) imaging. Magnetic resonance images were acquired for stereotactic planning for GKS of a vestibular schwannoma in a female patient. The images were acquired using three-dimensional sequence, which has been shown to produce minimal distortion effects. The images were transferred to the planning workstation, but the coronal images were rejected. By examination of the raw data and reconstruction of sagittal images through the localizer side plate, it was clearly seen that the image of the square localizer system was grossly distorted. The patient was returned to the MR imager for further studies and a metal clasp on her brassiere was identified as the cause of the distortion.A-60-year-old man with medically intractable left-sided maxillary division trigeminal neuralgia had severe cardiac disease, was dependent on an internal defibrillator and could not undergo magnetic resonance imaging. The patient was successfully treated using computerized tomography (CT) cisternography and gamma knife radiosurgery. The patient was pain free 2 months after GKS. Contrast cisternography with CT scanning is an excellent alternative imaging modality for the treatment of patients with intractable trigeminal neuralgia who are unable to undergo MR imaging.The authors describe acute deterioration in facial and acoustic neuropathies following radiosurgery for acoustic neuromas. In May 1995, a 26-year-old man, who had no evidence of neurofibromatosis Type 2, was treated with gamma knife radiosurgery (GKS; maximum dose 20 Gy and margin dose 14 Gy) for a right-sided intracanalicular acoustic tumor. Two days after the treatment, he developed headache, vomiting, right-sided facial weakness, tinnitus, and right hearing loss. There was a deterioration of facial nerve function and hearing function from pretreatment values. The facial function worsened from House-Brackmann Grade 1 to 3. Hearing deteriorated from Grade 1 to 5. Magnetic resonance (MR) images, obtained at the same time revealed an obvious decrease in contrast enhancement of the tumor without any change in tumor size or peritumoral edema. Facial nerve function improved gradually and increased to House-Brackmann Grade 2 by 8 months post-GKS. The tumor has been unchanged in size for 5 years, and facial nerve function has also been maintained at Grade 2 with unchanged deafness. This is the first detailed report of immediate facial neuropathy after GKS for acoustic neuroma and MR imaging revealing early possibly toxic changes. Potential explanations for this phenomenon are presented.In clinical follow-up studies after radiosurgery, imaging modalities such as computerized tomography (CT) and magnetic resonance (MR) imaging are used. Accurate determination of the residual lesion volume is necessary for realistic assessment of the effects of treatment. Usually, the diameters rather than the volume of the lesion are measured. To determine the lesion volume without using stereotactically defined images, the software program VOLUMESERIES has been developed. VOLUMESERIES is a personal computer-based image analysis tool. Acquired DICOM CT scans and MR image series can be visualized. The region of interest is contoured with the help of the mouse, and then the system calculates the volume of the contoured region and the total volume is given in cubic centimeters. The defined volume is also displayed in reconstructed sagittal and coronal slices. In addition, distance measurements can be performed to measure tumor extent. The accuracy of VOLUMESERIES was checked against stereotactically defined images in the Leksell GammaPlan treatment planning program. A discrepancy in target volumes of approximately 8% was observed between the two methods. This discrepancy is of lesser interest because the method is used to determine the course of the target volume over time, rather than the absolute volume. Moreover, it could be shown that the method was more sensitive than the tumor diameter measurements currently in use. VOLUMESERIES appears to be a valuable tool for assessing residual lesion volume on follow-up images after gamma knife radiosurgery while avoiding the need for stereotactic definition.This study was conducted to evaluate the geometric distortion of angiographic images created from a commonly used digital x-ray imaging system and the performance of a commercially available distortion-correction computer program. A 12 x 12 x 12-cm wood phantom was constructed. Lead shots, 2 mm in diameter, were attached to the surfaces of the phantom. The phantom was then placed inside the angiographic localizer. Cut films (frontal and lateral analog films) of the phantom were obtained. The films were analyzed using GammaPlan target series 4.12. The same procedure was repeated with a digital x-ray imaging system equipped with a computer program to correct the geometric distortion. The distortion of the two sets of digital images was evaluated using the coordinates of the lead shots from the cut films as references. The coordinates of all lead shots obtained from digital images and corrected by the computer program coincided within 0.5 mm of those obtained from cut films. The average difference is 0.28 mm with a standard deviation of 0.01 mm. On the other hand, the coordinates obtained from digital images with and without correction can differ by as much as 3.4 mm. The average difference is 1.53 mm, with a standard deviation of 0.67 mm. The investigated computer program can reduce the geometric distortion of digital images from a commonly used x-ray imaging system to less than 0.5 mm. Therefore, they are suitable for the localization of arteriovenous malformations and other vascular targets in gamma knife radiosurgery.

Results of Radiotherapy for Chemodectomas

Between 1974 and 1988, 10 Mayo Clinic patients had unresectable, locally recurrent, or partially resected chemodectomas. Of these 10 tumors, 9 were confirmed pathologically, and 1 was diagnosed clinically. The chemodectoma was located in the jugular bulb in five patients, the middle ear in three, and the carotid body in two. The following symptoms were noted: tinnitus (in eight patients), loss of hearing (in six), hoarseness (in six), dysphagia (in four), pain (in three), and alteration of mental status (in one). Many patients had more than one symptom. Treatment was delivered with megavoltage photons and electrons; total doses ranged from 16.2 to 52 Gy (median, 46 Gy), and the daily doses ranged from 1.6 to 2.4 Gy. Follow-up among the nine survivors ranged from 3 1/2 to 16 years (median, 7 1/2 years). In one patient, the response could not be assessed because the patient died of renal failure 4 months after treatment. All nine assessable patients had decreased symptoms and objective control of the tumor (no evidence of progression of disease). Of the nine assessable patients, four had complete responses, one had a partial response, and four had stable disease. No patient experienced progression of disease after radiotherapy. We conclude that radiotherapy for chemodectomas yields successful results--namely, decreased symptoms and objective control of the tumor.

Long-term tumor control and cranial nerve outcomes following Gamma knife surgery for larger-volume vestibular schwannomas: Clinical article

OBJECTnγ knife surgery (GKS) for vestibular schwannoma (VS) is an accepted treatment for small- to medium-sized tumors, generally smaller than 2.5 cm in the maximum posterior fossa dimension. The purpose of this study was to evaluate the efficacy and toxicity of GKS for larger tumors.nnnMETHODSnProspectively collected data were analyzed for 22 patients who had undergone GKS for VSs larger than 2.5 cm in the posterior fossa diameter between 1997 and 2006. No patient had symptomatic brainstem compression at the time of GKS. The median treated tumor volume was 9.4 cm(3) (range 5.3-19.1 cm(3)). The median maximum posterior fossa diameter was 2.8 cm (range 2.5-3.8 cm). The median tumor margin dose was 12 Gy (range 12-14 Gy). Serial imaging, audiometry (10 patients with serviceable hearing pre-GKS), and clinical follow-up were available for a median of 66 months (range 26-121 months). Tumor control failure was defined as either a progressive increase in tumor diameter of at least 2 mm in any dimension or a later resection.nnnRESULTSnFour patients met the criteria for GKS failure, including 1 patient who demonstrated sarcomatous degeneration more than 7 years after GKS and died 3 months after microsurgical debulking. An enlarging cystic component was the surgical indication in 1 of the 2 patients who required resection, although 27% of tumors (6 lesions) were cystic before GKS. The 3-year actuarial rate of tumor control, freedom from new facial neuropathy, and preservation of functional hearing were 86%, 92%, and 47%, respectively. At 5 years post-GKS, these rates decreased to 82%, 85%, and 28%, respectively. At the most recent follow-up, 91% of tumors were smaller than at the time of GKS and the median maximum posterior fossa diameter reduction was 26%. On multivariate analysis, none of the following factors was associated with GKS failure, new facial weakness, new trigeminal neuropathy, or loss of serviceable hearing: patient age, tumor volume, tumor margin dose, and preoperative cranial nerve dysfunction.nnnCONCLUSIONSnSingle-session radiosurgery is a successful treatment for the majority of patients with larger VSs. Although tumor control rates are lower than those for smaller VSs managed with GKS, the cranial nerve morbidity of GKS is significantly lower than that typically achieved via resection of larger VSs.

Failure rate of contemporary low-dose radiosurgical technique for vestibular schwannoma Clinical article

OBJECTnThe decline in cranial nerve morbidity after radiosurgery for vestibular schwannoma (VS) correlates with dose reduction and other technical changes to this procedure. The effect these changes have had on tumor control has not been well documented.nnnMETHODSnThe authors performed a retrospective review of 293 patients with VSs who underwent radiosurgery between 1990 and 2004 and had a minimum of 24 months of imaging follow-up (90% of the entire series). The median radiation dose to the tumor margin was 13 Gy. Treatment failure was defined as progressive tumor enlargement noted on 2 or more imaging studies. The mean postradiosurgical follow-up was 60.9 +/- 32.5 months.nnnRESULTSnTumor growth was noted in 15 patients (5%) at a median of 32 months after radiosurgery. Radiographically demonstrated tumor control was 96% at 3 years and 94% at 7 years after radiosurgery. Univariate analysis revealed 2 factors that correlated with failed radiosurgery for VS: an increasing number of isocenters (p = 0.03) and tumor margin radiation doses <or= 13 Gy (p = 0.02). Multivariate analysis showed that only an increasing number of isocenters correlated with failed VS radiosurgery (hazard ratio 1.1, 95% CI 1.02-1.32, p < 0.05). The tumor margin radiation dose (p = 0.22) was not associated with tumor growth after radiosurgery.nnnCONCLUSIONSnDistortion of stereotactic MR imaging coupled with increased radiosurgical conformality and progressive dose reduction likely caused some VSs to receive less than the prescribed radiation dose to the entire tumor volume.

Long-Term Outcome of Esthesioneuroblastoma: Hyams Grade Predicts Patient Survival

Objectu2003Esthesioneuroblastoma (ENB) is a rare malignant neuroendocrine tumor originating from the olfactory neuroepithelium in the cribriform plate. Controversy still exists regarding the role of pathologic grading (Hyams grade) in prognostication. This study was undertaken to describe our experience with ENB and assess the role of pathologic grading in patient outcome. Methodsu2003This was a retrospective, single-institution experience, including 109 patients with ENB treated at our institution from 1962 to 2009. Multivariate analysis was performed utilizing Cox regression analysis models utilizing age, gender, modified Kadish stage, and Hyams grade. Resultsu2003Mean age was 49u2009±u200916 (median 50) years at presentation (range 12 to 90 years). Median follow up was 5.1 years. All-cause mortality was significantly influenced by Hyams grading in univariate (pu2009=u20090.04) and multivariate (pu2009=u20090.02) analysis, in addition to proven prognostic factors, Kadish staging, lymph node metastasis, and age. Median survival was 9.8 years compared with 6.9 years with low (grade 1 to 2) versus high (grade 3 to 4) Hyams grade. Median overall survival was 7.2u2009±u20090.7 years. Conclusionu2003ENB has a variable outcome, which is primarily prognosticated by the extent of involvement at presentation (Kadish stage and lymph node metastasis) and higher Hyams pathologic grade.

Second primary tumors following tobacco dependence treatments among head and neck cancer patients.

Objectives:To estimate the cumulative percentage of second primary tumors (SPTs) in head and neck (H&N) cancer patients and primary cancers in general Nicotine Dependence Center (NDC) population controls following tobacco dependence consultation seen between 1988 and 2001. Methods:A 1:1 matched pair design and a stratified Cox proportional hazard model were used. General NDC population controls were matched on age, gender, and NDC consult (type and date) to the H&N cancer patients. The study population included 101 H&N cancer patients (66 male, 35 female) with mean (SD) age of 58.7 (10.1) years. Results:Baseline demographics and length of follow-up were similar between groups. However, H&N cancer patients smoked more cigarettes per day than controls (P < 0.003). For H&N cancer patients, the median time from initial H&N cancer diagnosis to NDC consult was 7 months (range, 0–292 months). Following the NDC consult, 27 H&N cancer patients developed 32 SPTs; whereas among the controls, 12 patients developed 12 other cancers (P = 0.013). There was no difference in the development of non–tobacco-related cancers (P = 0.273). However, H&N cancer patients were more likely to develop tobacco-related cancers (P = 0.01). Furthermore, there was a trend where the H&N cancer patients who continued to use tobacco were more likely to develop tobacco-related cancers than those who remained abstinent (P = 0.10). Conclusions:These findings confirm that H&N cancer patients are more prone to the development of tobacco-related cancers. Further, these findings suggest that H&N cancer patients who stop using tobacco are able to decrease the development of tobacco-related SPTs.

Locally Recurrent Non-Small-Cell Lung Cancer After Complete Surgical Resection

Between Jan. 1, 1976, and Dec. 31, 1985, at our institution, 37 patients who had undergone prior complete surgical resection of non-small-cell lung cancer received definitive thoracic radiation therapy (TRT) for locally recurrent disease. Of the 37 recurrences, 33 were in the pulmonary parenchyma or the hilar, mediastinal, or supraclavicular lymph nodes; the other 4 were in the chest wall. The initial stage of disease was I in 43%, II in 35%, and IIIA in 19%, whereas at the time of local recurrence, the stage was I in 8%, II in 11%, IIIA in 57%, IIIB in 22%, and IV in 3% (this patient had multiple pulmonary nodules encompassible within a single TRT field). The locally recurrent lesions were squamous cell carcinoma in 30%, adenocarcinoma or large-cell carcinoma in 46%, mixed types in 5%, and unknown type in 19%. All patients received megavoltage TRT, most often 4,000 cGy in 10 fractions administered in a split-course schedule. In addition, 15 patients received multiagent chemotherapy, usually a combination of cyclophosphamide, doxorubicin hydrochloride, and cisplatin or a regimen that included these drugs. The 2-year and 5-year survivals were 30% and 4%, respectively, and the median duration of survival was 13.7 months. Survival was not improved by the addition of chemotherapy. Approximately half of the patients had radiographic and symptomatic responses after TRT. Of 33 patients assessable for post-TRT patterns of failure, 46% had local failure only, 18% had local plus systemic failure, and 32% had systemic failure only. Two-thirds of the patients died as a direct consequence of progressive chest disease, despite receiving TRT.(ABSTRACT TRUNCATED AT 250 WORDS)

Doxepin Rinse Versus Placebo in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Head and Neck Radiotherapy With or Without Chemotherapy: A Phase III, Randomized, Double-Blind Trial (NCCTG-N09C6 [Alliance])

PURPOSEnPainful oral mucositis (OM) is a significant toxicity during radiotherapy for head and neck cancers. The aim of this randomized, double-blind, placebo-controlled trial was to test the efficacy of doxepin hydrochloride in the reduction of radiotherapy-induced OM pain.nnnPATIENTS AND METHODSnIn all, 155 patients were randomly allocated to a doxepin oral rinse or a placebo for the treatment of radiotherapy-related OM pain. Patients received a single dose of doxepin or placebo on day 1 and then crossed over to receive the opposite agent on a subsequent day. Pain questionnaires were administered at baseline and at 5, 15, 30, 60, 120, and 240 minutes. Patients were then given the option to continue doxepin. The primary end point was pain reduction as measured by the area under the curve (AUC) of the pain scale using data from day 1.nnnRESULTSnPrimary end point analysis revealed that the AUC for mouth and throat pain reduction was greater for doxepin (-9.1) than for placebo (-4.7; P < .001). Crossover analysis of patients completing both phases confirmed that patients experienced greater mouth and throat pain reduction with doxepin (intrapatient changes of 4.1 for doxepin-placebo arm and -2.8 for placebo-doxepin arm; P < .001). Doxepin was associated with more stinging or burning, unpleasant taste, and greater drowsiness than the placebo rinse. More patients receiving doxepin expressed a desire to continue treatment than did patients with placebo after completion of each of the randomized phases of the study.nnnCONCLUSIONnA doxepin rinse diminishes OM pain. Further studies are warranted to determine its role in the management of OM.