Evaluation of radiation treatment volumes for unknown primaries of the head and neck in the era of FDG PET.

OBJECTIVES: Positron-emission tomography (PET) has improved identification of the primary tumor as well as occult nodal burden in cancer of the head and neck. Nevertheless, there are still patients where the primary tumor cannot be located. In these situations, the standard of care is comprehensive head and neck radiation therapy however it is unclear whether this is necessary. This study examines the effects of radiation treatment volume on outcomes among using data from two cancer centers in unknown primary carcinoma of the head and neck. METHODS: Patients received unilateral (n = 34), or bilateral radiation (n = 28). Patient factors such as age, gender, smoking history, and patterns of failure were compared using Mann Whitney U and Chi Square. Overall survival (OS) and disease free survival (DFS) trends were estimated using Kaplan-Meier survival curves. Effect of treatment volume on survival was examined using multivariate cox proportional hazard regression model. RESULTS: No significant differences were observed in the frequency of local (p = 0.32), regional (p = 0.50), or distant (p = 0.76) failures between unilateral and bilateral radiation therapy. By Kaplan-Meier estimates, OS (3-year OS bilateral = 71.67%, unilateral = 77.90%, p = 0.50) and DFS (3-year DFS bilateral = 77.92%, unilateral = 69.43%, p = 0.63) were similar between the two treatment approaches. Lastly, multivariate analysis did not demonstrate any significant differences in outcome by treatment volumes (OS: HR = 0.74, 95% CI: 0.31, 1.81, p = 0.51; DFS: HR: 0.68, 95% CI: 0.24, 1.93, p = 0.47). CONCLUSIONS: Unilateral radiation therapy compared with bilateral produced similar survival.

Primary Mucinous Adenocarcinoma of the Upper Eyelid in an African American Female: A Rare Clinical Entity. A Case Report and Literature Review.

Primary mucinous adenocarcinoma (PMA) of the eyelid is a rare eccrine gland cancer with an incidence of 0.07 per million person-years. We report a case of a 62-year-old African American female who presented with a tender lesion over her left upper eyelid which was gradually progressive over four years. It was initially presumed to be benign but histopathology after excision was suggestive of a mucinous colloid carcinoma with positive margins. She underwent repeat excision with wide margins and reconstruction and immunohistochemical studies were suggestive of PMA. Workup for metastatic disease and rare possibility of underlying occult malignancy was negative. PMA is uncommon, more so in the African American population and in females. Given the uncommon occurrence of this tumor and similarities in histopathology to colon and breast cancers, underlying occult malignancies need to be ruled out prior to confirming the diagnosis of PMA. The most effective treatment modalities are Mohs micrographic surgery or excision with frozen section control of margins with regular follow up over a prolonged period of time. However, there are no large clinical studies with regard to treatment and follow up. More literature on this tumor would therefore be beneficial to clinicians.

Radiation-induced epithelial-myoepithelial carcinoma in a patient previously treated with mantle-field radiation therapy for Hodgkin lymphoma.

BACKGROUND: Radiation-induced salivary gland tumors are well described in the literature, with mucoepidermoid cancer being the most common histologic entity. Epithelial-myoepithelial carcinoma is a rare tumor accounting for <1% of all tumors in the salivary glands. METHODS AND RESULTS: We describe the first case of radiation-induced epithelial-myoepithelial carcinoma in the English-language medical literature. A 48-year-old man presented with right-sided mandibular pain and trismus, 25 years after mantle-field radiation therapy (RT) for Hodgkin lymphoma. He underwent excision of a right submandibular mass, which revealed a diagnosis of epithelial-myoepithelial carcinoma. Although typically a low-grade tumor, the histology revealed extensive necrosis and high mitotic activity. The patient required multiple resections and adjuvant therapy after multiple recurrences over a 4-year period. CONCLUSION: Reports of epithelial-myoepithelial carcinoma are relatively rare and this case highlights the importance of long-term follow-up and increased awareness of the risks of salivary gland tumors in this population.

Professional attitudes in regard to hyperbaric oxygen therapy for dental extractions in irradiated patients: a comparison of two specialties.

OBJECTIVES: Mandibular osteoradionecrosis (ORN) is a serious complication of radiation therapy. The current use of hyperbaric oxygen therapy (HBO2) to prevent ORN when dental extractions are performed has been called into question. We sought to determine the current acceptability and confidence in this treatment by practitioners from two different specialties. METHODS: We surveyed both hyperbaric medicine physicians and radiation oncologists regarding their views on the use of HBO2 for the prevention of ORN. Separate web-based anonymous surveys were sent via email invitation. These two groups were compared, including statistical analysis using the chi-square test when appropriate. RESULTS: 175 radiation oncologists and 118 hyperbaric medicine physicians participated. Among those not recommending HBO2, lack of evidence was cited by 52% of radiation oncologists and 38% of hyperbaric medicine physicians (chi2 = 5.0, p = 0.03, 95%, CI 1.9% to 25.6%). A majority of radiation oncologists (79%) and hyperbaric medicine physicians (85%) believe it is important that a new randomized controlled trial (RCT) is conducted (chi2 = 1.3, p = NS). CONCLUSIONS: While HBO2 has been used for decades, recent tissue-sparing radiation techniques and advanced surgical techniques are now calling into question the continued use of HBO2 for ORN prevention. Our results demonstrate that there is overwhelming support among responding practitioners for a new RCT.

Stereotactic radiosurgery in two cases of presumed fourth cranial nerve schwannoma.

A 47-year-old woman and a 45-year-old man with gradually progressive fourth cranial nerve palsy underwent stereotactic radiosurgery for presumed fourth cranial nerve schwannomas with the gamma knife at a marginal tumor dose of 14 and 13 Gy, respectively. In one patient, the ocular misalignment disappeared; in the other patient, it stabilized. MRI showed shrinkage of the tumors. These patients represent the second and third reported cases of presumed fourth cranial nerve schwannoma treated with radiosurgery and the first cases with substantial follow-up information.

Gamma Knife surgery in the management of radioresistant brain metastases in high-risk patients with melanoma, renal cell carcinoma, and sarcoma.

OBJECT: The purpose of this study was to examine the results of using Gamma Knife surgery (GKS) for brain metastases from classically radioresistant malignancies. METHODS: The authors retrospectively reviewed the records of 76 patients with melanoma (50 patients), renal cell carcinoma (RCC; 23 patients), or sarcoma (3 patients) who underwent GKS between August 1998 and July 2007. Overall patient survival, intracranial progression, and local progression of individual lesions were analyzed. RESULTS: The median age of the patients was 57 years (range 18-85 years) and median Karnofsky Performance Scale (KPS) score was 80 (range 20-100). Sixty-two patients (81.6%) had uncontrolled extracranial disease. A total of 303 intracranial lesions (average 3.97 per patient, range 1-27 lesions) were treated using GKS. More than 3 lesions were treated in 30 patients (39.5%). Median GKS tumor margin dose was 18 Gy (range 8-30 Gy). Thirty-seven patients (48.7%) underwent whole brain radiation therapy. The actuarial 12-month rate for freedom from local progression for individual lesions was 77.7% and was significantly higher for RCC compared with melanoma (93.6 vs 63.0%; p = 0.001). The percentage of coverage of the prescribed dose to target volume was the only treatment-related variable associated with local control: 12-month actuarial rate of freedom from local progression was 71.4% for lesions receiving >or= 90% coverage versus 0.0% for lesions receiving < 90% (p = 0.00048). Median overall survival was 5.1 months after GKS and 8.4 months after the discovery of brain metastases. Univariate analysis revealed that KPS score (p = 0.000004), recursive partitioning analysis class (p = 0.00043), and single metastases (p = 0.028), but not more than 3 metastases, to be prognostic factors of overall survival. The KPS score remained significant after multivariate analysis. Overall survival for patients with a KPS score >or= 70 was 7.1 months compared with 1.3 months for a KPS score 3 metastases. Higher rates of local tumor control were achieved for RCC in comparison with melanoma, and this may have an effect on survival in some patients. Although outcomes generally remained poor in this study population, these results suggest that GKS can be considered as a treatment option for many patients with radioresistant brain metastases, even if these patients have multiple lesions.

Gamma knife surgery for trigeminal neuralgia: improved initial response with two isocenters and increasing dose.

OBJECT: The authors sought to evaluate the initial response of trigeminal neuralgia (TN) to gamma knife surgery (GKS) based on the number of shots delivered and radiation dose. METHODS: Between September 1998 and September 2003, some 63 patients with TN refractory to medical or surgical management underwent GKS at Upstate Medical University. Ten patients had multiple sclerosis and 25 patients had undergone prior invasive treatment. Gamma knife surgery was delivered to the trigeminal nerve root entry zone in one shot in 27 patients or two shots in 36 patients. The radiation dose was escalated to less than or equal to 80 Gy in 20 patients, 85 Gy in 21 patients, and greater than or equal to 90 Gy in 22 patients. Pain before and after GKS was assessed using the Barrow Neurological Institute Pain Scale and the improvement score was analyzed as a function of dose grouping and number of shots. Sixty patients were available for evaluation, with an initial overall and complete response rate of 90% and 27%, respectively. There was a greater improvement score for patients who were treated with two shots compared with one shot, mean 2.83 compared with 1.72 (p < 0.001). There was an increased improvement in score at each dose escalation level: less than or equal to 80 Gy (p = 0.017), 85 Gy (p < 0.001), and greater than or equal to 90 Gy (p < 0.001). Linear regression analysis also indicated that there was a greater response with an increased dose (p = 0.021). Patients treated with two shots were more likely to receive a higher dose (p < 0.001). There were no severe complications. Five patients developed mild facial numbness. CONCLUSIONS: Gamma knife surgery is an effective therapy for TN. Initial response rates appear to correlate with the number of shots and dose.

A dwell position verification method for high dose rate brachytherapy.

Misplacement of dwell positions is a potential source of misadministration in high dose rate brachytherapy. In this work we present a dwell position verification method using fluoroscopic images. A mobile C-arm fluoroscopic machine is used to take a snapshot of the treatment machine's check cable as it reaches the most distal dwell position. This fluoroscopic image is displayed side-by-side with a treatment planning image on a dual monitor relay station at the HDR treatment console. Any discrepancy between the check cable's position on the verification image and the intended dwell position on the planning image can be identified immediately, thus avoiding the possibility of treating the wrong target volume.

Radiotherapy for the clinically negative neck in supraglottic laryngeal cancer.

PURPOSE: The supraglottic larynx has rich lymphatic drainage, resulting in a high incidence of occult cervical metastases, and the optimal treatment of the clinically uninvolved neck in supraglottic laryngeal cancer remains controversial. Selected retrospective series report a greater than 20% regional failure after treatment by radiotherapy alone, and some investigators recommend routine prophylactic neck dissection. We report on our series of patients who received radiotherapy as sole treatment to the clinically negative neck, either to the bilateral neck for N0 disease or to the contralateral neck for ipsilateral lymphatic involvement. PATIENTS AND METHODS: Between 1971 and 1998, 150 patients with supraglottic laryngeal cancer received radiotherapy alone to the clinically negative neck. Fifty-two patients had ipsilateral lymph node metastases (N1 = 16, N2a = 12, N2b = 20, N3 = 4), and 98 patients had no clinical nodal involvement. The primary site (T1/T2 = 74, T3/T4 = 76) was treated with radiotherapy (N = 91) or laryngectomy plus radiotherapy (N = 59). Neck dissection was performed on the involved neck in 36/52 node-positive patients for either multiple involved nodes (N = 20) or size > 3 cm (N = 16). Radiotherapy was delivered in standard fractionation and field arrangement. The median dose to the clinically negative neck was 5000 cGy (range: 4860-6000 cGy). RESULTS: With a median follow-up of 48 months, the clinically negative neck was the first site of failure in 3.3% of patients. The contralateral neck remained disease free in all patients. Five failures occurred in the N0 neck, and the median time to recurrence was 12 months (range: 5-30 months). Salvage therapy was neck dissection for the N0 neck failures. The 5-year locoregional control, disease-specific survival, and overall survival were 69%, 74%, and 61%, respectively. DISCUSSION: Our data support the use of radiotherapy as a prophylactic treatment for the clinically negative neck. Tumor control in the clinically uninvolved cervical lymphatics is comparable to that in surgical series, suggesting that routine neck dissection may not be necessary. Prospective trials are necessary to further define the role of radiotherapy in this patient population.

On the use of C-arm fluoroscopy for treatment planning in high dose rate brachytherapy.

Treatment planning for brachytherapy requires the acquisition of geometrical information of the implant applicator and the patient anatomy. This is typically done using a simulator or a computed tomography scanner. In this study, we present a different method by which orthogonal images from a C-arm fluoroscopic machine is used for high dose rate brachytherapy treatment planning. A typical C-arm is not isocentric, and it does not have the mechanical accuracy of a simulator. One solution is to place a reconstruction box with fiducial markers around the patient. However, with the limited clearance of the C-arm this method is very cumbersome to use, and is not suitable for all patients and implant sites. A different approach is adopted in our study. First, the C-arm movements are limited to three directions only between the two orthogonal images: the C-orbital rotation, the vertical column, and the horizontal arm directions. The amounts of the two linear movements and the geometric parameters of the C-arm orbit are used to calculate the location of the crossing point of the two beams and thus the magnification factors of the two images. Second, the fluoroscopic images from the C-arm workstation are transferred in DICOM format to the planning computer through a local area network. Distortions in the fluoroscopic images, with its major component the "pincushion" effect, are numerically removed using a software program developed in house, which employs a seven-parameter polynomial filter. The overall reconstruction accuracy using this method is found to be 2 mm. This filmless process reduces the overall time needed for treatment planning, and greatly improves the workflow for high dose rate brachytherapy procedures. Since its commissioning nearly three years ago, this system has been used extensively at our institution for endobronchial, intracavitary, and interstitial brachytherapy planning with satisfactory results.

The linear-quadratic model and fractionated stereotactic radiotherapy.

PURPOSE: To determine the dose per fraction that could be used when gamma knife or linear accelerator-based stereotactic treatments are delivered in 2 or more fractions. METHODS AND MATERIALS: The linear-quadratic (LQ) model was used to calculate the dose per fraction for a multiple-fraction regimen which is biologically equivalent to a given single-fraction treatment. The results are summarized in lookup tables. RESULTS AND CONCLUSION: The tables can be used by practicing clinicians as a guide in planning fractionated treatment. For the large doses used in typical stereotactic treatments and for small fraction numbers, the model is not very sensitive to the value of the alpha/beta ratio in the LQ model. A simple rule of thumb is found that for two-fraction and three-fraction treatments the dose per fraction is roughly two-thirds and one-half of the single-fraction treatment dose, respectively.

Radiotherapy for moderate-to-severe Graves' ophthalmopathy: improved outcomes with early treatment.

PURPOSE: The purpose of this review is to quantify the response to radiotherapy delivered early in the active inflammatory phase of moderate-to-severe Graves' ophthalmopathy. MATERIALS AND METHODS: A retrospective review of radiotherapy delivered early in the active phase of Graves' ophthalmopathy was performed. All 47 cases had moderate-to-severe ophthalmopathy, and 30 cases had optic neuropathy. Variables examined included exophthalmos, color vision, and resistance to retropulsion. Statistical analyses comparing these variables at presentation and at 3 and 6 months after radiotherapy were performed. Subset analyses comparing responses of patients with symptoms lasting longer or less than 6 months were also performed. RESULTS: At 6 months after radiotherapy, there was improvement in exophthalmos in 74.5% of cases and improvement in retropulsion in 83.0%, and all cases of previous color deficiency improved. The mean improvement in exophthalmos was 1.38 mm, color vision was two plates, and retropulsion was 1 grade. On subset analyses, there was a trend toward greater improvement in patients treated earlier in the course of their symptoms. CONCLUSIONS: Radiotherapy may play an important role in the treatment of Graves' ophthalmopathy, especially for patients with optic neuropathy. Early intervention (symptoms < 6 months) with radiotherapy may be the optimal timing for this treatment.

Successful treatment of spindle cell sarcoma of the sella turcica. Case report.

A primary spindle cell sarcoma of the sella turcica in a patient without a history of radiation treatment is a very rare occurrence. Only one other case has been reported to date, with local recurrence 7 months after the patient underwent subtotal resection and stereotactic radiosurgery of the tumor. The authors present a case of spindle cell sarcoma of the sella turcica successfully treated by surgery, external-beam radiotherapy, and gamma knife radiosurgery. After 24 months of follow up, the patient continues to show no evidence of disease.