Cranio-orbital Resection Does Not Appear to Improve Survival of Patients With Lacrimal Gland Carcinoma.

PURPOSE: To ascertain long-term outcome of treatment for primary epithelial malignancies of the lacrimal gland and compare outcomes after cranio-orbital resection or after macroscopic tumor resection with radiotherapy. METHODS: Comparative case series of 79 patients (49 male; 62%) treated for primary epithelial malignancies of the lacrimal gland at Moorfields Eye Hospital between 1972 and 2014. Patients were identified from clinical and pathological databases and, where available, the clinical, pathological, and imaging records reviewed. The primary outcome measures were overall survival after diagnosis, disease-free survival, and final visual acuity for patients having cranio-orbital resection (exenteration plus local bone removal), compared with macroscopic tumor resection plus radiotherapy. RESULTS: The mean age at presentation was 48 years (median: 50 years; range: 13-84 years), with 53 (67%) having adenoid cystic carcinoma, 15 (19%), primary adenocarcinoma, and 11 (14%) carcinoma ex-pleomorphic adenoma (malignant mixed tumor). The overall survival probability of the cohort (79 patients) was 0.59 at 5 years and 0.52 at 10 years, with 36/79 (46%) patients suffering tumor-related deaths; 14 patients died from other causes, and 4 patients were lost to follow up after the minimum follow-up period. The probability of disease-free survival at 5 years for patients with adenoid cystic carcinoma, adenocarcinoma, and malignant mixed tumor was 0.52, 0.4, and 0.64, respectively, with the comparable figures at 10 years being 0.44, 0.40, and 0.64. Most importantly, the 9 patients undergoing cranio-orbital resection and the 44 having solely macroscopic tumor resection plus radiotherapy had similar overall survival (p = 0.59) and disease-free survival (p = 0.89). Subgroup analysis of the 2 treatment modalities for patients with adenoid cystic carcinoma (8 cranio-orbital resection and 32 debulking and radiotherapy) demonstrated similar results for disease-free survival (p = 0.87). Likewise, there were no significant differences between rates of recurrences between the 2 different treatments. For the 50 patients who had eye-preserving surgery and long-term visual acuity data, the final acuity was better or equal to 0.6 logMAR (6/24 Snellen) in 25 (50%). DISCUSSION: There is no difference in either survival or tumor recurrence for lacrimal gland carcinoma treated with cranio-orbital resection, or eye-preserving tumor excision and radiotherapy. The authors, therefore, continue to advocate local resection and radiotherapy for almost all patients with primary epithelial malignancies of the lacrimal gland-this treatment having lower morbidity, causing less disfigurement, and, importantly, preserving useful vision in most patients.

Long-term outcomes of children treated for Cushing's disease: a single center experience.

PURPOSE: Pediatric Cushing's disease (CD) is rare and there are limited data on the long-term outcomes. We assessed CD recurrence, body composition, pituitary function and psychiatric comorbidity in a cohort of pediatric CD patients. METHODS: Retrospective review of 21 CD patients, mean age at diagnosis 12.1 years (5.7-17.8), managed in our center between 1986 and 2010. Mean follow-up from definitive treatment was 10.6 years (2.9-27.2). RESULTS: Fifteen patients were in remission following transsphenoidal surgery (TSS) and 5 were in remission following TSS + external pituitary radiotherapy (RT). One patient underwent bilateral adrenalectomy (BA). CD recurrence occurred in 3 (14.3 %) patients: 2 at 2 and 6 years after TSS and 1 7.6 years post-RT. The BA patient developed Nelson's syndrome requiring pituitary RT 0.6 years post-surgery. Short-term growth hormone deficiency (GHD) was present in 14 patients (81 % patients tested) (11 following TSS and 3 after RT) and 4 (44 % of tested) had long-term GHD. Gonadotropin deficiency caused impaired pubertal development in 9 patients (43 %), 4 requiring sex steroid replacement post-puberty. Four patients (19 %) had more than one pituitary hormone deficiency, 3 after TSS and 1 post-RT. Five patients (24 %) had long-term psychiatric co-morbidities (cognitive dysfunction or mood disturbance). There were significant long-term improvements in growth, weight and bone density but not complete reversal to normal in all patients. CONCLUSIONS: The long-term consequences of the diagnosis and treatment of CD in children is broadly similar to that seen in adults, with recurrence of CD after successful treatment uncommon but still seen. Pituitary hormone deficiencies occurred in the majority of patients after remission, and assessment and appropriate treatment of GHD is essential. However, while many parameters improve, some children may still have mild but persistent defects.

Evaluation of CyberKnife® Fiducial Tracking Limitations to Assist Targeting Accuracy: A Phantom Study with Fiducial Displacement.

Introduction  The underlying assumptions of the CyberKnife® (Accuray, Sunnyvale, CA, US) fiducial tracking system are: i) fiducial positions are accurately detected; ii) inter-fiducial geometry remains consistent (rigid); iii) inter-fiducial geometric array changes are detected and either accommodated with corrections or treatment is interrupted. However: i) soft-tissue targets are deformable & fiducial migration is possible; ii) the accuracy of the tracking system has not previously been examined with fiducial displacement; iii) treatment interruptions may occur due to inter-fiducial geometric changes, but there is little information available to assist subsequent troubleshooting. The purpose of this study was to emulate a clinical target defined with a two, three, or four-fiducial array where one fiducial is displaced to mimic a target deformation or fiducial migration scenario. The objectives: evaluate the fiducial positioning accuracy, array interpretation, & corresponding corrections of the CyberKnife system, with the aim of assisting troubleshooting following fiducial displacement. Methods A novel solid-water phantom was constructed with three fixed fiducials (F1,F2,F3) & one moveable fiducial (F4), arranged as if placed to track an imaginary clinical target. Using either two fiducials (F1,F4), different combinations of three fiducials (F1,F2,F4; F1,F3,F4; F2,F3,F4) or four fiducials (F1,F2,F3,F4), repeat experiments were conducted where F4 was displaced inferiorly at 2-mm intervals from 0-16 mm. Data were acquired at each position of F4, including rigid body errors (RBE), fiducial x, y, & z coordinate displacements, six degrees of freedom (DOF) corrections, & robot center-of-mass (COM) translation corrections. Results Maximum positioning difference (mean±SD) between the reference and live x, y, & z coordinates for the three fixed fiducials was 0.08±0.30 mm, confirming good accuracy for fixed fiducial registration. For two fiducials (F1,F4), F4 registration was accurate to 14-mm displacement and the F4 x-axis coordinate change was 2.0±0.12 mm with each 2 mm inferior displacement validating the phantom for tracking evaluation. RBE was >5 mm (system threshold) at 6-14 mm F4 displacement: however, F1 was misidentified as the RBE main contributor. Further, F1/F4 false-lock occurred at 16 mm F4 displacement with corresponding RBE <3 mm & COM corrections >13 mm. For combinations of three fiducials, F4 registration was accurate to 10-mm displacement. RBE was >5 mm at 6-16 mm F4 displacement: however, F4 false-lock occurred at 12-16 mm with RBE 5-6 mm. For four fiducials, F4 registration was accurate to 4 mm displacement: however, F4 false-lock occurred at 6-16 mm displacement with concerning RBE <2 & <5 at 6 & 8-mm F4 displacement, respectively. False-locks were easily identified in the phantom but frequently uncorrectable. Conclusions Results indicate fiducial positioning accuracy and system output following fiducial displacement depends on the number of fiducials correlated, displacement distance, and clinical thresholds applied. Displacements ≤4 mm were accurately located, but some displacements 6-16 mm were misrepresented, either by erroneous main contributor (two-fiducial array only) or by false-locks and misleading RBE, which underestimated displacement. Operator vigilance and implementation of our practical guidelines based on the study findings may help reduce targeting error and assist troubleshooting in clinical situations.

Corneal complications after orbital radiotherapy for primary epithelial malignancies of the lacrimal gland.

PURPOSE: To review the long-term corneal complications after high-dose external beam orbital radiotherapy given to patients for lacrimal gland carcinomas. The impact of prophylactic measures to improve long-term ocular surface health is also assessed. DESIGN: Retrospective case series. PARTICIPANTS: Patients under the care of Moorfields Eye Hospital and receiving external beam radiotherapy for primary epithelial lacrimal gland carcinoma between 1975 and 2014. METHODS: Retrospective review of ophthalmic case notes at Moorfields Eye Hospital, and oncology and general physician records. MAIN OUTCOME MEASURES: The occurrence of corneal perforation, and time to perforation. RESULTS: Sixty-seven patients were included in this study, of whom nine (13%) developed corneal perforation at a median time of 10.4 months after radiotherapy (mean 35; range 3.2 months to 14.5 years); the majority (7/9; 78%) perforated within 36 months of radiotherapy. The mean follow-up interval of the whole cohort was 8.2 years (median 4.6; range, 2 months to 30.7 years). CONCLUSIONS: Although most patients with globe-sparing treatment of lacrimal gland carcinoma did not suffer corneal perforation, they usually require long-term therapy to maintain the ocular surface. The high-dose external beam radiotherapy needed for lacrimal gland carcinoma can produce significant ocular surface morbidity, and the 13% incidence of corneal perforation was greatest in the first 3 years after irradiation.