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ABSTRACT: PURPOSE: To compare the dose distributions and late radiation toxicities for (125)I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma. METHODS: Ninety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean doses at predetermined intraocular points were calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the log-rank test compared the estimates. RESULTS: The median follow-up was 46 months in both cohorts. The 2 cohorts were balanced with respect to pretreatment clinical and tumor characteristics. Comparisons of radiation toxicity rates between the IBT and SRT cohorts yielded actuarial rates at 50 months for cataracts of 62% and 75% (P=.1), for neovascular glaucoma 8% and 47% (P=.002), for radiation retinopathy 59% and 89% (P=.0001), and for radiation papillopathy 39% and 74% (P=.003), respectively. Dosimetric comparisons between the IBT and SRT cohorts yielded mean doses of 12.8 and 14.1 Gy (P=.56) for the lens center, 17.6 and 19.7 Gy (P=.44) for the lens posterior pole, 13.9 and 10.8 Gy (P=.30) for the ciliary body, 61.9 and 69.7 Gy (P=.03) for optic disc center, and 48.9 and 60.1 Gy (P<.0001) for retina at 5-mm distance from tumor margin, respectively. CONCLUSIONS: Late radiation-induced toxicities were greater with SRT, which is secondary to the high-dose exposure inherent to the technique as compared with IBT. When technically feasible, IBT is preferred to treat juxtapapillary choroidal melanoma.
International journal of radiation oncology, biology, physics 03/2013; · 4.59 Impact Factor
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ABSTRACT: AIMS: To compare the treatment efficacy and radiation complications between (125)Iodine brachytherapy and stereotactic radiotherapy in the management of juxtapapillary choroidal melanoma. METHODS: Consecutive juxtapapillary melanoma patients treated with radiotherapy were included. Patients were divided into two cohorts: patients treated with (125)Iodine brachytherapy and patients with stereotactic radiotherapy. Comparison included the rates postradiotherapy local recurrence, secondary enucleation, metastasis and radiotherapy complications. Kaplan-Meier estimates were used to determine the actuarial rates, and logrank test to compare between the estimates. RESULTS: We included 94 patients with juxtapapillary melanoma treated with radiotherapy. The brachytherapy cohort included 30 patients and stereotactic radiotherapy was 64. The median follow-up was 46 months in both cohorts. No statistically significant differences existed between the two cohorts on comparing pretreatment clinical data and tumour characteristics. On comparing treatment efficacy, the actuarial rates at 50 months for tumour recurrence were 11% and 7% (p=0.61), secondary enucleation was 11% and 21% (p=0.30) and for metastasis were 4% and 16% (p=0.11), respectively. On comparing treatment complications, the actuarial rates at 50 months for cataracts were 62% and 75% (p=0.1), for neovascular glaucoma 8% and 47% (p=0.002), for radiation retinopathy 59% and 89% (p=0.0001), and for radiation papillopathy 39% and 74% (p=0.003), respectively. CONCLUSIONS: Both (125)Iodine brachytherapy and stereotactic radiotherapy demonstrate comparable efficacy in the management of juxtapapillary choroidal melanoma. However, stereotactic radiotherapy shows statistically significant higher radiation-induced ocular morbidities at 4 years postradiotherapy.
The British journal of ophthalmology 01/2013; · 2.92 Impact Factor
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ABSTRACT: BACKGROUND: The loss of tumor suppressor gene (TSG) function is a critical step in the pathogenesis of human lung cancer. RBM5 (RNA-binding motif protein 5, also named H37/LUCA-15) gene from chromosome 3p21.3 demonstrated tumor suppressor activity. However, the role of RBM5 played in the occurrence and development of lung cancer is still not well understood. METHOD: Paired non-tumor and tumor tissues were obtained from 30 adenocarcinomas. The expression of RBM5 mRNA and protein was examined by RT-PCR and Western blot. A549 cell line was used to determine the apoptotic function of RBM5 in vitro. A549 cells were transiently transfected with pcDNA3.1-RBM5. AnnexinV analysis was performed by flow cytometry. Expression of Bcl-2, cleaved caspase-3, caspase-9 and PAPP proteins in A549 lung cancer cells and the A549 xenograft BALB/c nude mice model was determined by Western blot. Tumor suppressor activity of RBM5 was also examined in the A549 xenograft model treated with pcDNA3.1-RBM5 plasmid carried by attenuated Salmonella typhi Ty21a. Result The expression of RBM5 mRNA and protein was decreased significantly in adenocarcinoma tissues compared to that in the non-tumor tissues. In addition, as compared to the vector control, a significant growth inhibition of A549 lung cancer cells was observed when transfected with pcDNA3.1-RBM5 as determined by cell proliferation assay. We also found that overexpression of RBM5 induced both early and late apoptosis in A549 cells using AnnexinV/PI staining as determined by flow cytometry. Furthermore, the expression of Bcl-2 protein was decreased, whereas the expression of cleaved caspase-3, caspase-9 and PARP proteins was significantly increased in the RBM5 transfected cells; similarly, expression of decreased Bcl-2 and increased cleaved caspase-3 proteins was also examined in the A549 xenograft model. More importantly, we showed that accumulative and stable overexpression of RBM5 in the A549 xenograft BALB/c nude mice model significantly inhibited the tumor growth rate in vivo as compared to that in the control. CONCLUSION: Our study demonstrates that RBM5 can inhibit the growth of lung cancer cells and induce apoptosis both in vitro and in vivo, which suggests that RBM5 might be used as a potential biomarker or target for lung cancer diagnosis and chemotherapy. Moreover, we propose a novel animal model set up in BALB/c nude mice treated with attenuated Salmonella as a vector carrying plasmids to determine RBM5 function in vivo.
World Journal of Surgical Oncology 08/2012; 10(1):160. · 1.12 Impact Factor
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ABSTRACT: We aimed to derive three-dimensional volume-based (V(3D)) response criteria that approximate those based on Response Evaluation Criteria in Solid Tumours (RECIST) in patients with brain metastases (BM) treated with salvage stereotactic radiosurgery (SRS).
Seventy patients with 178 BM were treated with SRS. Each BM was characterised at baseline and at each follow-up MRI according to its widest diameter and V(3D) using ITK-SNAP image segmentation software.
The median tumour diameter was 1.2 cm (range, 0.2-4.5 cm) and V(3D) was 0.73 cm(3) (range, 0.01-22.7 cm(3)). The V(3D) percent changes that best matched RECIST response criteria were: an increase of ≥71.5% for progressive disease, a ≥58.5% decrease for partial response and a <58.5% decrease or increase of <71.5% for stable disease (k =0.85). A baseline diameter >3.0 cm (p =0.006) and a V(3D) >6.0 cm(3) (p =0.043) predicted for local failure, and a baseline cumulative V(3D) of >3.0 cm(3) (p =0.02) was adversely prognostic for survival.
We define 3D volume specific criteria to base response upon for brain metastases treated with salvage SRS. Tumours with a V(3D) of greater than 6 cm(3) are at a higher risk of local failure.
Acta oncologica (Stockholm, Sweden) 04/2012; 51(5):629-35. · 2.27 Impact Factor
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ABSTRACT: RNA binding motif 5 (RBM5) is a tumor suppressor gene that modulates apoptosis through the regulation of alternative splicing of apoptosis-related genes. This study aimed to detect RBM5 expression in non-small cell lung cancer (NSCLC) and to associate RBM5 expression with clinicopathological data from NSCLC patients and EGFR and KRAS expression to better understand the potential role of RBM5 in NSCLC.
Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to detect expression of mRNA and protein, respectively, of RBM5, EGFR and KRAS in 120 paired non-tumor and tumor samples of NSCLC.
The data showed that expression of RBM5 mRNA and protein was significantly reduced in NSCLC compared to normal tissues, whereas expression of both EGFR and KRAS genes was increased in NSCLC compared to normal tissues. Furthermore, the reduced RBM5 protein expression correlated with smoking status, tumor stage and lymph node metastasis of NSCLC, while overexpression of EGFR and KRAS proteins correlated with tumor stage and lymph node metastasis of NSCLC. Overexpression of KRAS protein was more frequent in smokers with NSCLC. In addition, expression of RBM5 mRNA and protein was negatively correlated with expression of EGFR and KRAS mRNA and protein in NSCLC tissues.
This study suggests further evaluation of RBM5 expression is warranted for use of RBM5 as a biomarker for NSCLC patients.
Journal of Experimental & Clinical Cancer Research 04/2012; 31:36. · 2.15 Impact Factor
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Elena S Koltun,
Amy Lew Tsuhako,
David S Brown,
Naing Aay,
Arlyn Arcalas,
Vicky Chan,
Hongwang Du,
Stefan Engst,
Kim Ferguson,
Maurizio Franzini, [......],
Gordon Stott,
Thomas J Stout,
Jenny Young,
Peiwen Yu,
Cristiana A Zaharia,
Wentao Zhang,
Peiwen Zhou,
John M Nuss, Wei Xu,
Patrick C Kearney
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ABSTRACT: CDC7 is a serine/threonine kinase that has been shown to be required for the initiation and maintenance of DNA replication. Up-regulation of CDC7 is detected in multiple tumor cell lines, with inhibition of CDC7 resulting in cell cycle arrest. In this paper, we disclose the discovery of a potent and selective CDC7 inhibitor, XL413 (14), which was advanced into Phase 1 clinical trials. Starting from advanced lead 3, described in a preceding communication, we optimized the CDC7 potency and selectivity to demonstrate in vitro CDC7 dependent cell cycle arrest and in vivo tumor growth inhibition in a Colo-205 xenograft model.
Bioorganic & medicinal chemistry letters 04/2012; 22(11):3727-31. · 2.65 Impact Factor
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Amy Lew Tsuhako,
David S Brown,
Elena S Koltun,
Naing Aay,
Arlyn Arcalas,
Vicky Chan,
Hongwang Du,
Stefan Engst,
Maurizio Franzini,
Adam Galan, [......],
Michael Pack,
Gordon Stott,
Thomas J Stout,
Peiwen Yu,
Cristiana Zaharia,
Wentao Zhang,
Peiwen Zhou,
John M Nuss,
Patrick C Kearney, Wei Xu
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ABSTRACT: A series of substituted benzofuropyrimidinones with pan-PIM activities and excellent selectivity against a panel of diverse kinases is described. Initial exploration identified aryl benzofuropyrimidinones that were potent, but had cell permeability limitation. Using X-ray crystal structures of the bound PIM-1 complexes with 3, 5m, and 6d, we were able to guide the SAR and identify the alkyl benzofuropyrimidinone (6l) with good PIM potencies, permeability, and oral exposure.
Bioorganic & medicinal chemistry letters 04/2012; 22(11):3732-8. · 2.65 Impact Factor
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ABSTRACT: Brain metastases represent a significant healthcare problem. It is estimated that 20% to 40% of patients with cancer will develop metastatic cancer to the brain during the course of their illness. The burden of brain metastases impacts on quality and length of survival. Presenting symptoms include headache (49%), focal weakness (30%), mental disturbances (32%), gait ataxia (21%), seizures (18%), speech difficulty (12%), visual disturbance (6%), sensory disturbance (6%) and limb ataxia (6%).Brain metastases may spread from any primary site. The most common primary site is the lung, followed by the breast then gastrointestinal sites. Eighty-five per cent of brain metastases are found in the cerebral hemispheres, 10% to 15% in the cerebellum and 1% to 3% in the brainstem. Brain radiotherapy is used to treat cancer participants who have brain metastases from various primary malignancies.This is an update to the original review published in Issue 3, 2006.
To assess the effectiveness and adverse effects of whole brain radiotherapy (WBRT) in adult participants with multiple metastases to the brain.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2011), MEDLINE and EMBASE to July 2011.
Randomized controlled trials (RCTs) comparing WBRT either alone or with other treatments in adults with newly diagnosed multiple metastases to the brain from any primary cancer. Trials of prophylactic WBRT were excluded as well as trials that dealt with surgery or WBRT, or both, for the treatment of single brain metastasis.
Two review authors independently assessed trial quality and abstracted information. Adverse effects information was also collected from the trials.
Nine RCTs involving 1420 participants were added in this updated review. This updated review now includes a total of 39 trials involving 10,835 participants.Eight published reports (nine RCTs) showed no benefit of altered dose-fractionation schedules as compared to the control fractionation (3000 cGy in 10 fractions daily) of WBRT for overall survival. These studies also showed no improvement in symptom control nor neurologic improvement among the different dose-fractionation schemes as compared to 3000 cGy in 10 daily fractions of WBRT. This updated review includes two trials comparing 4000 cGy in 20 fractions given twice daily versus 2000 cGy in 4 or 5 daily fractions. Overall, there was no survival advantage (hazard ratio (HR) 1.18, 95% confidence interval (CI) 0.89 to 1.56, P = 0.25) with the use of 4000 cGy in 20 fractions given twice daily compared to 2000 cGy in 4 or 5 daily fractions.The addition of radiosensitizers in six RCTs did not confer additional benefit to WBRT in either the overall survival times (HR 1.08, 95% CI 0.98 to 1.18, P = 0.11) or brain tumour response rates (HR 0.87, 95% CI 0.60 to 1.26, P = 0.46).Two RCTs found no benefit in overall survival (HR 0.61, 95% CI 0.27 to 1.39, P = 0.24) with the use of WBRT and radiosurgery boost as compared to WBRT alone for selected participants with multiple brain metastases (up to four brain metastases). Overall, there was a statistically significant improvement in local brain control (HR 0.35, 95% CI 0.20 to 0.61, P = 0.0003) favouring the WBRT and radiosurgery boost arm. Only one trial of radiosurgery boost with WBRT reported an improved Karnofsky performance score outcome and improved ability to reduce the dexamethasone dose.In this updated review, a total of three RCTs reported on selected patients (with up to three or four brain metastases) treated with radiosurgery alone versus WBRT and radiosurgery. Based on two trials, there was no difference in overall survival (HR 0.98, 95% CI 0.71 to 1.35, P = 0.88). The addition of WBRT when added to radiosurgery significantly improved locally treated brain metasatases control (HR 2.61, 95% CI 1.68 to 4.06, P < 0.0001) and distant brain control (HR 2.15, 95% CI 1.55 to 2.99, P < 0.00001). On the other hand, one trial concluded that patients treated with WBRT and radiosurgery boost were significantly more likely to show a decline in learning and memory function as compared to those treated with radiosurgery alone.One RCT examined the use of WBRT and prednisone versus prednisone alone and produced inconclusive results.
None of the RCTs with altered WBRT dose-fractionation schemes as compared to standard (3000 cGy in 10 daily fractions or 2000 cGy in 4 or 5 daily fractions) found a benefit in terms of overall survival, neurologic function, or symptom control.The use of radiosensitizers or chemotherapy in conjunction with WBRT remains experimental.Radiosurgery boost with WBRT may improve local disease control in selected participants as compared to WBRT alone, although survival remains unchanged for participants with multiple brain metastases.This updated review now includes a total of three RCTs examining the use of radiosurgery alone versus WBRT and radiosurgery. The addition of WBRT to radiosurgery improves local and distant brain control but there is no difference in overall survival. Patients treated with radiosurgery alone were found to have better neurocognitive outcomes in one trial as compared to patients treated with WBRT and radiosurgery.The benefit of WBRT as compared to supportive care alone has not been studied in RCTs. It may be that supportive care alone, without WBRT, is appropriate for some participants, particularly those with advanced disease and poor performance status.
Cochrane database of systematic reviews (Online) 01/2012; 4:CD003869. · 5.72 Impact Factor
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ABSTRACT: To perform a meta-analysis on newly diagnosed brain metastases patients treated with whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) boost versus WBRT alone, or in patients treated with SRS alone versus WBRT and SRS boost.
The meta-analysis primary outcomes were overall survival (OS), local control (LC), and distant brain control (DBC). Secondary outcomes were neurocognition, quality of life (QOL), and toxicity. Using published Kaplan-Meier curves, results were pooled using hazard ratios (HR).
Two RCTs reported on WBRT and SRS boost versus WBRT alone. For multiple brain metastases (2-4 tumors) we conclude no difference in OS, and LC significantly favored WBRT plus SRS boost. Three RCTs reported on SRS alone versus WBRT plus SRS boost (1-4 tumors). There was no difference in OS despite both LC and DBC significantly favoring WBRT plus SRS boost. Although secondary endpoints could not be pooled for meta-analysis, those RCTs evaluating SRS alone conclude better neurocognition using the validated Hopkins Verbal Learning Test, no adverse risk in deteriorating Mini-Mental Status Exam scores or in maintaining performance status, and fewer late toxicities. We conclude insufficient data for QOL outcomes.
For selected patients, we conclude no OS benefit for WBRT plus SRS boost compared with SRS alone. Although additional WBRT improves DBC and LC, SRS alone should be considered a routine treatment option due to favorable neurocognitive outcomes, less risk of late side effects, and does not adversely affect the patients performance status.
Cancer 09/2011; 118(9):2486-93. · 4.77 Impact Factor
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MD Adrian Ishkanian MSc,
Normand J. Laperriere MD,
Wei Xu PhD,
Barbara-Ann Millar MD,
David Payne MD,
Warren Mason MD,
Arjun Sahgal MD,
Adrian Ishkanian,
Normand J. Laperriere, Wei Xu,
Barbara‐Ann Millar,
David Payne,
Warren Mason,
Arjun Sahgal
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ABSTRACT: BACKGROUND:Although pilocytic astrocytoma accounts for up to 40% of all childhood brain tumors, it is a rare disease in adults. Consequently, there are few mature data on the impact of up-front treatment options after surgery that include observation or adjuvant radiotherapy.METHODS:Ten women and 20 men were identified who were diagnosed with pilocytic astrocytoma from 1971 to 2007 and were retrospectively reviewed. The median patient age was 30 years (range, 18-64 years), and the median follow-up was 87 months (range, 16-420 months). Initial surgery included biopsy (10% of patients), subtotal resection (57% of patients), or gross-total resection (33% of patients). Nineteen patients were observed postoperatively, whereas 11 patients received up-front postoperative adjuvant radiotherapy (50 grays in 25 fractions). No patient received adjuvant or concurrent chemotherapy. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Differences between survival curves were analyzed with the log-rank test.RESULTS:For the entire cohort, the 5-year and 10-year OS rates were 95% and 85%, respectively, and the 5-year and 10-year PFS rates were 63% and 35%, respectively. The median PFS was 8.4 years. Initial radiation, compared with observation, did not have an impact on OS but significantly improved PFS. The 5-year PFS rate for patients who were observed versus those who received radiation was 42% versus 91%, respectively; and, at 10 years, the PFS rate was 17% versus 60%, respectively (P = .005). Patients who progressed after observation (11 of 19 patients) received various salvage therapies, resulting in a 2-year PFS rate of 68% compared with 33% for patients who progressed after initial radiation (3 of 11 patients) and were salvaged with either chemotherapy or surgery (P = .1).CONCLUSIONS:Adjuvant radiotherapy for pilocytic astrocytoma significantly prolonged PFS at both 5 years and 10 years compared with observation. However, equivalent OS was observed, which reflected the efficacy of salvage therapies. Cancer 2011;. © 2011 American Cancer Society.
Cancer 08/2011; 117(17):4070 - 4079. · 4.77 Impact Factor
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Bruno F Fernandes,
Daniel Weisbrod,
Yeni H Yücel,
Matthew Follwell,
Hatem Krema,
Mostafa Heydarian, Wei Xu,
David Payne,
Hugh McGowan,
Ernest R Simpson,
Normand Laperriere,
Arjun Sahgal
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ABSTRACT: Enucleation after stereotactic radiotherapy (SRT) for juxtapapillary choroidal melanoma may be required because of tumor progression (TP) or the development of intractable radiation-induced neovascular glaucoma (NVG). We compare pathologic changes and dosimetric findings in those eyes enucleated secondary to NVG as opposed to TP to better understand potential mechanisms.
Patients with juxtapapillary choroidal melanoma treated with SRT (70 Gy in 5 fractions, alternate days over a total of 10 days) at the Princess Margaret Hospital, Toronto, Ontario, Canada, who underwent enucleation between 1998 and 2006 were selected. We correlated dosimetric data based on the patient's original SRT treatment plan with histopathologic findings in the retina, optic nerve head, and anterior chamber. A dedicated ocular pathologist reviewed each case in a blinded fashion.
Ten eyes in ten patients were enucleated after SRT. Six were enucleated secondary to NVG and four secondary to because of TP. Aggressive tumor features such as invasion of the sclera and epithelioid cell type were observed predominantly in the TP group. Retinal damage was more predominant in the NVG group, as were findings of radiation-related retinal vascular changes of fibrinoid necrosis and hyalinization. No conclusive radiation-related effects were found in the anterior chamber. The maximum point dose and dose to 0.1 cc were lower for the anterior chamber as compared with the dose to the tumor, retina, and optic nerve head. The mean 0.1-cc doses to the retina were 69.4 Gy and 73.5 Gy and to the anterior chamber were 4.9 Gy and 17.3 Gy for the NVG group and tumor progression group, respectively.
Our findings suggest that NVG is due to radiation damage to the posterior chamber of the eye rather than primary radiation damage to the anterior segment.
International journal of radiation oncology, biology, physics 06/2011; 80(2):377-84. · 4.59 Impact Factor
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ABSTRACT: To report the host, tumour, and radiation-related predictive factors for developing radiation retinopathy post (125)Iodine brachytherapy for uveal melanoma.
A retrospective clinical case series.
Three hundred consecutive patients with uveal melanoma treated with (125)Iodine brachytherapy.
Electronic chart review of demographic, clinical, treatment, and follow-up data. Proliferative and (or) nonproliferative radiation retinopathy patients were included. Cumulative incidence rates were calculated using Kaplan-Meier estimates. Univariate and multivariate statistical regression analyses were performed to identify factors predictive of radiation retinopathy.
The mean follow-up period was 48 months. Radiation retinopathy occurred in 107 patients (36%). Actuarial incidence of radiation retinopathy was 30% (CI 24%-36%) at 24 months post-treatment. In the multivariate model, the predictive factors were a younger age (hazard ratio [HR] 0.98, p < 0.03), diabetes (HR 2.17, p < 0.007), and hypertension (HR 2.17, p < 0.004). Tumour-related factors were proximity to optic disc (HR 0.95, p < 0.02) and proximity to foveola (HR 0.96, p < 0.02). Pretreatment tumour dimensions, other tumour characteristics, and total radiation dose did not demonstrate statistically significant risks for developing radiation retinopathy.
Radiation retinopathy affects 30% of patients 2 years following (125)Iodine brachytherapy for uveal melanoma. The predictive factors for radiation retinopathy are a younger age, comorbidity with diabetes or hypertension, and proximity of the tumour margin to the optic disc or foveola. Identifying the predictive factors for developing radiation retinopathy can modify follow-up for patients at risk, which may permit earlier management of the developing radiation-induced ischemic retinal changes.
Canadian Journal of Ophthalmology 04/2011; 46(2):158-63. · 1.47 Impact Factor
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ABSTRACT: Although pilocytic astrocytoma accounts for up to 40% of all childhood brain tumors, it is a rare disease in adults. Consequently, there are few mature data on the impact of up-front treatment options after surgery that include observation or adjuvant radiotherapy.
Ten women and 20 men were identified who were diagnosed with pilocytic astrocytoma from 1971 to 2007 and were retrospectively reviewed. The median patient age was 30 years (range, 18-64 years), and the median follow-up was 87 months (range, 16-420 months). Initial surgery included biopsy (10% of patients), subtotal resection (57% of patients), or gross-total resection (33% of patients). Nineteen patients were observed postoperatively, whereas 11 patients received up-front postoperative adjuvant radiotherapy (50 grays in 25 fractions). No patient received adjuvant or concurrent chemotherapy. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Differences between survival curves were analyzed with the log-rank test.
For the entire cohort, the 5-year and 10-year OS rates were 95% and 85%, respectively, and the 5-year and 10-year PFS rates were 63% and 35%, respectively. The median PFS was 8.4 years. Initial radiation, compared with observation, did not have an impact on OS but significantly improved PFS. The 5-year PFS rate for patients who were observed versus those who received radiation was 42% versus 91%, respectively; and, at 10 years, the PFS rate was 17% versus 60%, respectively (P = .005). Patients who progressed after observation (11 of 19 patients) received various salvage therapies, resulting in a 2-year PFS rate of 68% compared with 33% for patients who progressed after initial radiation (3 of 11 patients) and were salvaged with either chemotherapy or surgery (P = .1).
Adjuvant radiotherapy for pilocytic astrocytoma significantly prolonged PFS at both 5 years and 10 years compared with observation. However, equivalent OS was observed, which reflected the efficacy of salvage therapies.
Cancer 03/2011; 117(17):4070-9. · 4.77 Impact Factor
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ABSTRACT: To establish the growth behavior of small ciliary body tumors in a relatively large cohort of patients over an extended period.
Retrospective, noncomparative case series.
Ciliary body tumors less than 4 mm in size within the penetration power of ultrasound biomicroscopy (UBM) were included. Tumor height was assessed by ultrasound biomicroscopy. Tumor growth was defined as an increase in height of at least 20% from baseline, as measured on 2 consecutive UBM readings. The data were collected longitudinally, and a statistical analysis was performed.
Forty-two patients were included in the study with a median follow-up of 9.0 years (range, 1.0 to 17.2 years). The median age was 59 years (range, 17 to 82 years). Median initial tumor height was 2.05 mm (range, 1.11 to 3.80 mm). The overall average rate of growth was 0.0014 mm per year (P = .68). The 5- and 10-year accumulative tumor growth rates were 12% and 29%, respectively. In the first 3 years after diagnosis, the growth rate of ciliary body lesions with an initial tumor thickness less than or equal to 2 mm was 0.054 mm per year (P = 0.0001); thereafter, tumor size appeared to stabilize. Tumors with an initial thickness greater than 2 mm showed a small but significant rate of regression of 0.0125 mm per year (P = 0.04).
Most small tumors of the ciliary body show little growth over an extended period and can be managed conservatively without invasive diagnostic interventions. However, long-term follow-up is required. Indications for treatment include growth in height or lateral extension, extrascleral extension or the need for cataract surgery.
American journal of ophthalmology 04/2010; 149(4):616-22. · 3.83 Impact Factor
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ABSTRACT: To report the treatment outcomes and complication rates of stereotactic radiotherapy in the management of patients with juxtapapillary choroidal melanoma.
A retrospective review of 64 consecutive patients with juxtapapillary choroidal melanoma, located within 2 mm of the optic disc, treated with stereotactic radiotherapy at Princess Margaret Hospital between October 1998 and January 2006.
The median age was 63 years. The median tumour height was 4.2 mm, and median largest basal diameter was 9.8 mm. The prescribed radiation dose was 70 Gy in five fractions over 10 days, and the median follow-up was 37 months. Post-treatment, the actuarial rates of local tumour control, metastases and survival at 37 months were 94%, 15% and 90%, respectively. Actuarial rates of radiation-induced complications at 37 months were neovascular glaucoma 42%, cataract 53%, retinopathy 81% and optic neuropathy 64%. Secondary enucleation was necessary for 10 patients (16%), in four patients for tumour recurrence and in six for painful neovascular glaucoma.
Stereotactic radiotherapy offers a non-invasive alternative to enucleation and brachytherapy in the management of juxtapapillary choroidal melanoma with a high tumour control rate, however, at the expense of a significant rate of long-term ocular complications.
The British journal of ophthalmology 06/2009; 93(9):1172-6. · 2.92 Impact Factor
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ABSTRACT: To evaluate the efficacy and complications of stereotactic radiotherapy in the management of patients with juxtapapillary choroidal melanoma.
Retrospective review.Participants: 64 patients with juxtapapillary choroidal melanoma.
Consecutive patients with juxtapapillary choroidal melanomas located within 2 mm of the optic nerve, treated with stereotactic radiotherapy at Princess Margaret Hospital from October 1998 to January 2006, were reviewed for treatment effect and complication rates.
Median age was 63 years. Median tumor height was 4.2 mm, and median maximum tumor diameter was 9.8 mm. The prescribed radiation dose was 70 Gy in 5 fractions over 10 days, and the median follow-up was 26 months. After treatment, there was local tumor recurrence in 3 patients, and in 8 patients there was systemic progression. Actuarial rates of local tumor control, metastases, and survival at 26 months were 94%, 12%, and 94%, respectively. Rates of radiation-induced neovascular glaucoma, cataract, retinopathy, and optic neuropathy at 26 months were 28%, 45%, 80%, and 52%, respectively. Enucleation was necessary for 7 patients.
Stereotactic radiotherapy offers a noninvasive alternative with acceptable ocular toxicity rates to enucleation and brachytherapy in the management of juxtapapillary choroidal melanoma.
Canadian Journal of Ophthalmology 03/2009; 44(1):61-5. · 1.47 Impact Factor
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Arjun Sahgal,
Christopher Ames,
Dean Chou,
Lijun Ma,
Kim Huang, Wei Xu,
Cynthia Chin,
Vivan Weinberg,
Cynthia Chuang,
Phillip Weinstein,
David A Larson
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ABSTRACT: To provide actuarial outcomes and dosimetric data for spinal/paraspinal metastases, with and without prior radiation, treated with stereotactic body radiotherapy (SBRT).
A total of 39 consecutive patients (60 metastases) were treated with SBRT between April 2003 and August 2006 and retrospectively reviewed. In all, 23 of 60 tumors had no previous radiation (unirradiated) and 37/60 tumors had previous irradiation (reirradiated). Of 37 reirradiated tumors, 31 were treated for "salvage" given image-based tumor progression. Local failure was defined as progression by imaging and/or clinically.
At last follow-up, 19 patients were deceased. Median patient survival time measured was 21 months (95% CI = 8-27 months), and the 2-year survival probability was 45%. The median total dose prescribed was 24 Gy in three fractions prescribed to the 67% and 60% isodose for the unirradiated and reirradiated cohorts, respectively. The median tumor follow-up for the unirradiated and reirradiated group was 9 months (range, 1-26) and 7 months (range, 1-48) respectively. Eight of 60 tumors have progressed, and the 1- and 2-year progression-free probability (PFP) was 85% and 69%, respectively. For the salvage group the 1 year PFP was 96%. There was no significant difference in overall survival or PFP between the salvage reirradiated vs. all other tumors treated (p = 0.08 and p = 0.31, respectively). In six of eight failures the minimum distance from the tumor to the thecal sac was <or=1 mm. Of 60 tumors treated, 39 have >or=6 months follow-up and no radiation-induced myelopathy or radiculopathy has occurred.
Spine SBRT has shown preliminary efficacy and safety in patients with image-based progression of previously irradiated metastases.
International journal of radiation oncology, biology, physics 01/2009; 74(3):723-31. · 4.59 Impact Factor
