Evolution of asymmetric proptosis during the active phase of thyroid eye disease.

PURPOSE: To assess the evolution of proptosis asymmetry during the active phase of bilateral thyroid eye disease (TED). METHODS: A retrospective study was conducted on patients with bilateral, active TED. Patients were measured by a single observer, using Hertel exophthalmometry from the time of initial presentation, during the active phase of TED, to the stable phase, 24-months later. Asymmetric proptosis was defined as a >2 mm intra-orbital difference in Hertel measurements. RESULTS: Fifty-one patients were enrolled. Patients presented at a mean time of 1.1 ± 2.9 months following the onset of TED symptoms. Stability of TED was established at 15.7 ± 12.3 months. At initial presentation, 41% of patients demonstrated asymmetric proptosis. Upon reaching the stable phase, asymmetric proptosis persisted in only 22% of patients. A decline in the rate asymmetric proptosis was greatest within the first 3 months of the active phase. CONCLUSIONS: Asymmetric proptosis is common in the setting of early active TED and decreases by 50% when the stable phase is reached. Therefore, diagnostic imaging is not routinely required to exclude alternative pathology in the cases of asymmetric TED. Perhaps more importantly, this finding supports the surgical paradigm of stable phase, graded orbital decompression, performed when the ultimate globe positions are achieved to avoid late postoperative asymmetry, resulting from the unanticipated evolution of proptosis when surgery is performed during the active phase of TED.

A 27-YEAR-OLD FEMALE WITH MILD BLURRY VISION AND PROLONGED LIGHT ADJUSTMENT IN THE MORNING.

PURPOSE: The following case report highlights a rare presentation of chronic myeloid leukemia-associated hyper-viscosity syndrome and provides a brief review of expected findings and treatment outcomes. METHODS: An otherwise healthy 27-year-old woman presented to the ophthalmology clinic with mild bilateral blurriness (20/20 in both eyes) and prolonged light adaption in the morning for several months. Examination demonstrated severe bilateral venous stasis, white-centered hemorrhages, intraretinal hemorrhage, and peripheral ischemia with diffuse leakage. RESULTS: Same-day CBC demonstrated a leukocytosis of >600,000. Subsequent bone marrow biopsy confirmed the 9,22 translocation (Philadelphia chromosome). On further examination, the patient had an enlarged cardiac silhouette, cytopenia, and splenomegaly past the umbilicus, consistent with a severe and life-threatening leukostasis. CONCLUSION: Ocular involvement can occur in acute and chronic leukemia. Five to ten percentage of patients present to an eye physician first, without a known diagnosis. Prompt systemic treatment can result in near-complete reversal of any intraocular injury in most mild-to-moderate cases, as was the case here.

Macular Findings in Carriers of Ocular Albinism With a Novel GPR143 Mutation.

This case series details macular findings in three female siblings who were found to be carriers of a previously unreported splice mutation in GPR143 (X-linked ocular albinism [OA1]). Presumed lyonization is responsible for both the subtle and varied findings in OA1 carriers, even among siblings, and especially in patients with darker skin pigmentation. In this series, we used green-light autofluorescence to reveal subtle subfoveal involvement and used optical coherence tomography angiography to uncover previously unreported narrowing of the foveal avascular zone, consistent with foveal hypoplasia. [Ophthalmic Surg Lasers Imaging Retina 2022;53:460-463.].

A Case of Brainstem Anesthesia after Retrobulbar Block for Globe Rupture Repair.

PURPOSE: To present a rare case of brainstem anesthesia from retrobulbar block and discuss evidence-based methods for reducing the incidence of this complication. CASE: A 72-year-old female, was given a retrobulbar block of 5 mL of bupivacaine 0.5% for postoperative pain management, after a globe rupture repair under general anesthesia. Prior to injection, the patient was breathing spontaneously via the anesthesia machine circuit and had not received any additional narcotics/muscle relaxants for 2.5 hr (with full recovery of neuromuscular blocking agent after anesthetic reversal). Over 7 min, however, there was a steady increase in ETCO2 and the patient became apneic, consistent with brainstem anesthesia. She remained intubated and was transported to the postanesthesia care unit for prolonged monitoring, with eventual extubation. Discussion. Brainstem anesthesia is an important complication to recognize as it can lead to apnea and death. The judicious use of anesthetic volume, shorter needle tips, and mixed formulations can help reduce the chance of brainstem anesthesia. Observation of the contralateral eye 5-10 minutes after injection for pupillary dilation, and prior to surgical draping, can help identify early CNS involvement.

Tacrolimus induced optic neuropathy in post-lung transplant patients: A series of 3 patients.

PURPOSE: Tacrolimus is a commonly used immunosuppressant medication after lung transplantation. In rare cases, tacrolimus causes a medication-induced optic neuropathy (TON) that can lead to significant vision loss. OBSERVATIONS: In this series, we describe three cases of TON, 1-10 years after medication use. Two patients were young (22yr and 33yr) females with cystic fibrosis. The last case was a 65yr male with idiopathic pulmonary fibrosis. In 2/3 cases tacrolimus serum levels were normal. Visual acuity ranged from 20/20 to 20/300, and vision loss occurred acutely to sub-acutely, over a span of 2-3 months. CONCLUSIONS AND IMPORTANCE: As presented here, TON can be highly variable. MRI findings are often non-specific, from normal brain findings to extensive white matter changes. There remains an unclear association with graft-versus-host disease and reduced kidney function. Visual findings are often subtle, including color vision aberration and peripheral visual field deficits, both of which usually require an ophthalmologic evaluation. When diagnosed in a timely fashion, TON is at least partially reversible in up to half of all cases. While rare, the cases described here support post-lung transplant ophthalmologic evaluation in those taking high-risk medications.

The Challenge of Managing Bilateral Acute Angle-closure Glaucoma in the Presence of Active SARS-CoV-2 Infection.

PURPOSE: To report a case of bilateral acute angle-closure glaucoma associated with hyponatremia in the setting of chlorthalidone use and SARS-CoV-2 infection, and to demonstrate the challenges of managing this patient given her infectious status. METHODS: This was a case report. CASE: A 65-year-old woman taking chlorthalidone for hypertension presented to the emergency room with headache, pain, and blurry vision in both eyes and was found to be in bilateral acute angle closure. On laboratory investigation, she was severely hyponatremic and also tested positive for SARS-CoV-2. B-scan ultrasound demonstrated an apparent supraciliary effusion in the right eye. Following stabilization of her intraocular pressures with medical management, she ultimately underwent cataract extraction with iridectomies and goniosynechiolysis in both eyes. CONCLUSIONS: We report a rare case of bilateral acute angle-closure glaucoma associated with hyponatremia. Chlorthalidone use and perhaps SARS-CoV-2 infection may have contributed to this electrolyte abnormality and unique clinical presentation. In addition, we discuss the challenges of managing this complex patient with active SARS-CoV-2 infection during the pandemic.

Contour Variability in Thyroid Eye Disease with Compressive Optic Neuropathy Treated with Radiation Therapy.

PURPOSE: Few studies have evaluated the methodology by which radiation therapy (RT) for thyroid eye disease and compressive optic neuropathy is performed. The objective of this study was to retrospectively review our experience from a radiation planning standpoint and to determine whether current treatment methods provide adequate dose to target and collateral structures. METHODS: A retrospective review of 52 patients (104 orbits) with bilateral thyroid eye disease and compressive optic neuropathy treated with RT (20 Gy in 10 fractions) at our institution. RT plans were analyzed for target volumes and doses. Visual fields, color plates, and visual acuity were assessed pretreatment and at last available follow-up post RT. A standardized, anatomic contour of the retro-orbital space was applied to these retrospective plans to determine dose to the entire space, rather than the self-selected target structure. RESULTS: Compared with the anatomic retro-orbital space, the original contour overlapped by only 68%. Maximum and mean dose was 2134 cGy and 1910 cGy to the anatomic retro-orbital space. Consequently, 39.8% of the orbits had a mean dose <19 Gy (<17 Gy 16.4%, <18 Gy 27.6% <19 Gy 37.8%, <20 Gy 59.2%, 20-21 Gy 35.8%, >21 Gy 5%). There was no significant association of improvement in color plates (P = .07), visual fields (P = .77), and visual acuity (P = .62), based on these dose differences. When beam placement was retrospectively adjusted to include a space of 0.5 cm between the lens and the anterior beam edge, there was a 39.4% and 20.3% decrease in max and mean dose to the lens. CONCLUSIONS: Without a standardized protocol for contouring in thyroid eye disease, target delineation was found to be rather varied, even among the same practitioner. Differences in dose to the anatomic retro-orbital space did not affect outcomes in the follow-up period. Although precise contouring of the retro-orbital space may be of little clinical consequence overall, a >0.5 cm space from the lens may significantly reduce or delay cataractogenesis.

Natural history, clinical course and predictors of interval time from initial diagnosis to development of subsequent NSCLC brain metastases.

PURPOSE: Non-small cell lung cancer (NSCLC) brain metastases are associated with substantial morbidity and mortality. During recent years, accompanying dramatic improvements in systemic disease control, NSCLC brain metastases have emerged as an increasingly relevant clinical problem. However, optimal surveillance practices remain poorly defined. This purpose of this study was to further characterize the natural history, clinical course and risk factors associated with earlier development of subsequent NSCLC brain metastases to better inform clinical practice and help guide survivorship care. METHODS: We retrospectively reviewed all institutional NSCLC brain metastasis cases treated with radiotherapy between 1997 and 2015. Exclusion criteria included presence of brain metastases at initial NSCLC diagnosis and incomplete staging information. Interval time to brain metastases and subsequent survival were characterized using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: Among 105 patients within this cohort, median interval time to development of brain metastases was 16 months. Median interval times were 29, 19, 16 and 13 months for Stage I-IV patients, respectively (P = 0.016). Additional independent predictors for earlier development of NSCLC brain metastases included non-adenocarcinomatous histopathology (HR 3.036, P < 0.001), no prior surgical resection (HR 1.609, P = 0.036) and no prior systemic therapy (HR 3.560, P = 0.004). Median survival following intracranial progression was 16 months. Delayed development of brain metastases was associated with better prognosis (HR 0.970, P < 0.001) but not survival following intracranial disease onset. CONCLUSIONS: Collectively, our results provide valuable insights into the natural history of NSCLC brain metastases. NSCLC stage, histology, prior surgical resection and prior systemic therapy emerged as independent predictors for interval time to brain metastases.

OPHTHALMIC FINDINGS IN LATE STAGE SJOGREN-LARSSON SYNDROME.

PURPOSE: To report spectral domain optical coherence tomography and fundus autofluorescence documentation of late stage macular findings associated with Sjogren-Larsson Syndrome in three adult siblings. METHODS: Three adult siblings with Sjogren-Larsson Syndrome underwent ophthalmic examination and imaging. RESULTS: Crystalline maculopathy and subretinal deposits, presumably lipofuscin accumulation, with macular atrophy were present in varying degrees in all three adult siblings. DISCUSSION: In adults with Sjogren-Larsson Syndrome, crystalline retinopathy can progress to macular atrophy and the appearance of lipofuscin accumulation.

Eye-Drop Abstinence in Glaucoma Patients Admitted to the Hospital Service: A Single Institution Assessment.

PURPOSE: Anecdotally, many patients admitted to an inpatient general medicine service do not have their glaucoma eye drops started. The purpose of this study was to determine the extent of eye-drop abstinence after inpatient admission. DESIGN: Retrospective, cross-sectional, hospital-based study. PARTICIPANTS: Four hundred seventy-five patients admitted to the general medicine regional hospital service from January 2016 through February 2018 with a known past medical diagnosis of or active outpatient medications for glaucoma. METHODS: The combination of an administrative database and cross-referenced patient charts were reviewed for demographic data, past medical problems, inpatient orders, intake history and physical, length of stay, and admitting diagnosis. MAIN OUTCOME MEASURES: The effect of (1) outpatient glaucoma drops reconciliation and (2) recognition of glaucoma as a pertinent past medical problem in a patient's intake history and physical on inpatient eye-drop administration. The overall rate of eye-drop abstinence also was recorded. RESULTS: Of 475 patients, 46.3% were women, with an average age of 80.2 years (standard deviation, 11.1 years). Average length of stay was 4.61 days (standard deviation, 3.7 days). In total, 63.8% achieved successful administration of medication on the hospital floor, resulting in a 36.2% eye-drop abstinence rate during the hospital stay. Three hundred eighty-six of 475 patients (81.3%) achieved successful glaucoma medication reconciliation. Patients with successful reconciliation had a significantly different rate of eye-drop administration (73.3% vs. 21.0%; P ≤ 0.001). Recognition of glaucoma in the history and physical occurred in only 42.5% of patients. There was a significant difference in eye-drop administration when glaucoma was included in the history and physical (75.7% vs. 55.0%; P ≤ 0.001). CONCLUSIONS: Glaucoma treatment incurs a high rate of medication noncompliance, especially in the elderly. The present study demonstrates that more than one third of patients admitted to an academic medical center do not receive their glaucoma medications. Patients discharged to nursing homes, subacute rehabilitation, and assisted living facilities rely on appropriate discharge medication reconciliation, resulting in forced abstinence during transition of care. An emphasis on appropriate medical reconciliation and recognition of glaucoma as a pertinent past medical problem will improve rates of eye-drop discontinuation on inpatient admission significantly.

Age-Related Changes in the Clinical Phenotype of Compressive Optic Neuropathy in Thyroid Eye Disease.

PURPOSE: This study compares the age-related clinical features of thyroid eye disease-compressive optic neuropathy (TED-CON) to those with noncompressive disease (TED-NC). METHODS: A retrospective case series review of 165 orbits from 121 patients with TED-CON were compared with an age- and gender-matched cohort of 88 orbits from 44 patients with TED-NC with institutional review board approval. Clinical features including exophthalmos, dyschromatopsia, restricted ocular motility, visual acuity, and mean deviation on 24-2 Humphrey Visual Field were compared in 5 age groups. A previously validated formula, the Columbia TED-CON Diagnostic formula, used to mathematically predict the presence or absence of compressive optic neuropathy was applied, and the sensitivity and specificity of the formula was measured in each age group. RESULTS: Exophthalmos, dyschromatopsia, restricted ocular motility, and mean deviation on 24-2 Humphrey Visual Field vary significantly across age groups in patients with TED-CON. Conversely, only visual acuity and dyschromatopsia vary significantly across age groups in patients with TED-NC. There was a significant difference between the TED-CON and the TED-NC groups when comparing the 2 groups by decade. The Columbia TED-CON Diagnostic formula had high sensitivity and specificity (74-90%) in all age groups. CONCLUSIONS: This is the first study to date demonstrating the age-related variability of clinical characteristics in a large series of patients with either TED-CON or TED-NC. The clinical phenotype of TED-CON varies significantly by decade when examining exophthalmos, dyschromatopsia, ocular motility restriction, and mean deviation on 24-2 Humphrey Visual Field. These clinical characteristics are also significantly different when compared with a population of patients with TED-NC.

Greater Proptosis Is Not Associated With Improved Compressive Optic Neuropathy in Thyroid Eye Disease.

PURPOSE: Despite the paucity of supporting data, it has generally been held that proptosis in thyroid eye disease (TED) may provide relative protection from compressive optic neuropathy (CON) by producing spontaneous decompression. The objective of this study was to investigate this phenomenon in patients with bilateral TED-CON. METHODS: We retrospectively reviewed the charts of 67 patients (134 orbits) with bilateral TED-CON at Columbia-Presbyterian Medical Center. Significant asymmetric proptosis (Hertel) was defined as ≥ 2 mm. Significant asymmetric CON was defined first, as the presence of an relative afferent pupillary defect. Those without an relative afferent pupillary defect were evaluated according to the TED-CON formula y = -0.69 - 0.31 × (motility) - 0.2 × (mean deviation) - 0.02 × (color vision) as previously established for the diagnosis of TED-CON. A difference in the formula result ≥ 1.0 between eyes was considered significant. Patients were then divided into 4 groups. RESULTS: Forty-one of 67 patients demonstrated asymmetric CON (29 by relative afferent pupillary defect, 12 by formula). Twenty-one of 67 patients demonstrated asymmetric proptosis. Only 5 of 12 (41.6%) of the patients who had both asymmetric proptosis and asymmetric CON (group 1) showed greater proptosis in the eye with less CON. Twenty-nine patients (group 2) showed that asymmetric CON occurred despite symmetrical proptosis. Seventeen patients (group 3), showed the inverse, that asymmetric differences in proptosis occurred with symmetrical CON. CONCLUSION: Despite commonly held assumptions, our results suggest that greater proptosis is not associated with improved TED-CON. Combining groups 1 to 3-all of which demonstrated asymmetry of either proptosis, CON, or both-91.4% of patients did not show a relationship between greater proptosis and improved CON.

Local control and overall survival for adjuvant stereotactic radiosurgery in patients with residual or recurrent disease.

Prior studies of post-operative stereotactic radiosurgery (SRS) have not distinguished between Adjuvant SRS (ARS) versus Adjuvant SRS to residual/recurrent disease (ARD). In this study, we defined ARS and ARD and investigated local control (LC), overall survival (OS), distant development of brain metastases (DBF), and leptomeningeal disease (LMD). We retrospectively identified BM patients who received surgical resection and SRS for BM from an IRB approved database between Jan 2009-Aug 2015. Patients were stratified into two groups: ARS and ARD. LC was determined by follow-up MRI studies and OS was measured from the date of surgery. LC and OS were assessed using the Kaplan-Meier method. 70 cavities underwent surgical resection of BM and received SRS to the post-operative bed. 41 cavities were classified as ARS and 29 as ARD. There was no significant difference in 12-month LC between the ARS and ARD group (71.4 vs. 80.8%, respectively; p = 0.135) from the time point of SRS. The overall 1-year survival for ARS and ARD was 79.9 and 86.1%, respectively (p = 0.339). Mean time to progression was 6.45 and 8.0 months and median follow-up was 10 and 15 months for ARS and ARD, respectively. 11.8% of ARS patients and 15.4% of ARD patients developed LMD, p = 0.72. 29.4% of ARS and 48.0% of ARD patients developed DBF, p = 0.145. Our findings suggest that observation after surgical resection, with subsequent treatment with SRS after the development of local failure, may not compromise treatment efficacy. If validated, this would spare patients who do not recur post-surgically from additional treatment.

Risk of dry eye syndrome in patients treated with whole-brain radiotherapy.

With improvements in systemic therapy, patients with cancer treated with whole-brain radiotherapy (WBRT) are living long enough to develop late toxicities, including dry eye syndrome. In general practice, dose to the lacrimal gland (LG) is not constrained (maximum constraint <40 Gy) in WBRT. The purpose of this study was to measure dose to the LG in WBRT and determine methods for reducing radiation exposure. We conducted a retrospective review of 70 3-dimensional (3D) conformal plans; thirty-six plans with a radiation prescription of 30 Gy in 10 fractions and 34 plans with a prescription of 37.5 Gy in 15 fractions. LGs were contoured in accordance with Freedman and Sidani (2015). Biological effective dose (BED)3 maximum constraints were calculated from 40 Gy and 20 Gy to be 32.17 Gy (30 Gy) and 36.70 Gy (37.5 Gy). Both regimens demonstrated supraorbital blocking by 3 methods: T1, bordering the supraorbital ridge; T2, no contact with supraorbital ridge; and T3, coverage of the supraorbital ridge. Mean dose for the plans with a 30-Gy prescription and the plans with a 37.5-Gy prescription was 27.5 Gy and 35.2 Gy, respectively (p ≤ 0.0001). BED3 maximum constraint (Dmax) was violated 16 of 26 (61.5%) in T1 (average Dmax: 32.2 Gy), 13 of 28 (46.4%) in T2 (average Dmax: 32.1 Gy), and 5 of 18 (27.8%) in T3 (average Dmax: 31.8 Gy) for the 30-Gy prescription. Dmax was violated in 32 of 32 (100%) in T1 (average Dmax: 40.1 Gy), 22 of 22 (100%) in T2 (average Dmax: 40.3 Gy), and 14 of 14 (100%) in T3 (average Dmax: 39.4) for the 37.5 Gy prescription. Average Dmax for the 37.5-Gy prescription was highly significant in favor of T3 (p = 0.0098). Patients who receive WBRT may develop dry eye syndrome as a late toxicity. Constraints are commonly violated with a prescription of 37.5 Gy. Methods to reduce dose include T3 supraorbital blocking, an easily implementable change that may dramatically improve patient quality of life.

Ophthalmic Timolol Hallucinations: A Case Series and Review of the Literature.

PURPOSE: Systemic absorption and central nervous system (CNS) penetration of timolol drops are a well-studied phenomenon, resulting in common side effects such as bradycardia, bronchospasm, fatigue, and confusion. More serious CNS side effects, such as psychosis and depression, however, are rarely attributed to eye drops. We report a case series in which patients developed visual hallucinations secondary to topical ocular timolol use. METHODS: This study is a case series and review of the literature. RESULTS: Four patients with glaucoma developed visual hallucinations while using topical timolol. The patients were all elderly, caucasian females with associated CNS pathology. All patients had resolution of symptoms upon discontinuation and a positive retrial test to confirm the association. CONCLUSIONS: The rarity of this side effect and its anecdotal predilection for elderly, caucasian females with underlying neurological dysfunction, may involve a yet unknown predisposition or hypersensitivity to beta blocker action, such as blood brain barrier disruption leading to increased susceptibility to the medication. This case series highlights an important, although rare, side effect of this medication which clinicians should be aware of especially when using it in elderly patients who may have coexisting CNS pathology. It is important that this side effect be recognized and appropriately managed to prevent otherwise unnecessary investigations and treatment.

Breast cancer subtype as a predictor for outcomes and control in the setting of brain metastases treated with stereotactic radiosurgery.

We investigated effects of breast cancer subtype on overall survival (OS), local and distant control, and time from initial diagnosis to brain metastases (BM). We also investigated advances in graded prognostic assessment (GPA) scores. A cohort of 72 patients treated for BM from breast cancer with Gamma Knife stereotactic radiosurgery at our institution from 2000 to 2014 had subtyping available and were used for this study. Median follow up for OS was 12 months and for control was 6 months. OS for luminal, HER2, and triple negative subtypes were 26, 20, and 22 months. OS when stratified by Sperduto et al. (J Clin Oncol 30(4):419-425, 2012) and Subbiah et al. (J Clin Oncol 33(20):2239-2245, 2015) GPAs were similar (p = 0.087 and p = 0.063). KPS and treatment modality were significant for OS (p = 0.002; p = 0.034). On univariate analysis, triple negative subtype and >3 BM were trending and significant for decreased OS (p = 0.084; p = 0.047). On multivariable analysis HER2, triple negative, and >3 BM were significant for OS (p = 0.022; p = 0.040; p = 0.009). Subtype was significant for response on a per lesion basis (p = 0.007). Subtype was trending towards significance when analyzing time from initial diagnosis to BM treatment (p = 0.064). Breast cancer subtype is an important prognostic factor when stratifying breast cancer patients with BM. The addition of number of BM to the GPA is a useful addition and should be further investigated. Subtype has an effect on lesion response, and also on rate of development BM after initial diagnosis.

Control of brain metastases from radioresistant tumors treated by stereotactic radiosurgery.

Renal cell carcinoma, sarcoma, and melanoma are considered to be "radioresistant" tumor histologies. Brain metastases (BM) from these tumors are considered unlikely to be controlled using the relatively low doses used in whole brain radiotherapy (WBRT). Our objective was to analyze the efficacy of stereotactic radiosurgery (SRS) on local control and overall survival of BM from radioresistant primary tumors. We reviewed all patients who received Gamma Knife Radiosurgery (GKRS) for BM at Columbia University Medical Center between January 2009 and April 2014. All patients were treated using the Gamma Knife Perfexion System. Dosimetric data was collected from treatment plans and metastases were categorized as radioresistant or not. Response was assessed by reviewing follow-up brain imaging studies and classified according to RECIST. Local control and median overall survival were calculated using the Kaplan-Meier method. In total, 373 tumors were analyzed from 126 patients. Of these tumors, 49 (13.1 %) originated from radioresistant cancers. The overall local control rate in the radioresistant cohort was 89.8 and 90.1 % in the non-radioresistant cohort. Univariate and multivariate analyses demonstrated that radioresistance status of the primary tumor had no statistically significant effect on local control with hazard ratios of 1.0 (p = 1.0, 95 % CI 0.388-2.576) and 0.954 (p = 0.926, 95 % CI 0.349-2.603) respectively. Median overall survival for both radioresistant and non-radioresistant cohorts was 20.0 months, with a p value of 0.926. There was no significant difference in local control of BM from radioresistant and non-radioresistant primary tumors treated with GKRS. Both cohorts showed excellent response and local control, suggesting that SRS upfront or in addition to WBRT may be an appropriate strategy in the treatment of BM from radioresistant cancers. Median overall survival for both cohorts was equal, suggesting that improved local control may be associated with an improvement in long-term survival.