Roy Ma

A Comparison of Volumetric Modulated Arc Therapy and Conventional Intensity-Modulated Radiotherapy for Frontal and Temporal High-Grade Gliomas

PURPOSE Volumetric modulated arc therapy (VMAT), the predecessor to Varians RapidArc, is a novel extension of intensity-modulated radiotherapy (IMRT) wherein the dose is delivered in a single gantry rotation while the multileaf collimator leaves are in motion. Leaf positions and the weights of field samples along the arc are directly optimized, and a variable dose rate is used. This planning study compared seven-field coplanar IMRT (cIMRT) with VMAT for high-grade gliomas that had planning target volumes (PTVs) overlapping organs at risk (OARs). METHODS AND MATERIALS 10 previously treated patients were replanned to 60 Gy in 30 fractions with cIMRT and VMAT using the following planning objectives: 98% of PTV covered by 95% isodose without violating OAR and hotspot dose constraints. Mean OAR doses were maximally decreased without reducing PTV coverage or violating hotspot constraints. We compared dose-volume histogram data, monitor units, and treatment times. RESULTS There was equivalent PTV coverage, homogeneity, and conformality. VMAT significantly reduced maximum and mean retinal, lens, and contralateral optic nerve doses compared with IMRT (p < 0.05). Brainstem, chiasm, and ipsilateral optic nerve doses were similar. For 2-Gy fractions, mean monitor units were as follows: cIMRT = 789 +/- 112 and VMAT = 363 +/- 45 (relative reduction 54%, p = 0.002), and mean treatment times (min) were as follows: cIMRT = 5.1 +/- 0.4 and VMAT = 1.8 +/- 0.1 (relative reduction 65%, p = 0.002). CONCLUSIONS Compared with cIMRT, VMAT achieved equal or better PTV coverage and OAR sparing while using fewer monitor units and less time to treat high-grade gliomas.

Meningiomas in 2009: controversies and future challenges.

Meningiomas are the most common intracranial primary neoplasm in adults. Over recent years, interest in this clinically diverse group of tumors has intensified, bringing new questions and challenges to the fore, particularly in the fields of epidemiology, radiology, pathology, genetics, and treatment. Interest in modern meningioma research has been stimulated by the high tumor prevalence and the advances in technology. The incidence of meningiomas is climbing, and may indicate increased exposure to environmental risk factors or more sensitive diagnostic modalities. Technological advances have dramatically improved radiologic imaging and radiotherapy treatments, and further refinements are under investigation. Furthermore, the current era of tumor genetics and molecular biology is challenging translational researchers to discover new, targeted, therapeutic agents. This review is an update on the recent advances in the understanding of meningiomas and their management, and highlights pertinent research questions to be addressed in the future.

Hearing preservation following fractionated stereotactic radiotherapy for vestibular schwannomas: prognostic implications of cochlear dose

OBJECT The goal in this study was to evaluate hearing preservation rates and to determine prognostic factors for this outcome following fractionated stereotactic radiotherapy (FSRT) of vestibular schwannoma. METHODS Thirty-four consecutive patients with serviceable hearing who received FSRT between May 1998 and December 2003 were identified. Clinical and audiometry data were collected prospectively. The prescription dose was 45 Gy in 25 fractions prescribed to the 90% isodose line. The median follow-up duration was 36.5 months (range 12-85 months). The actuarial 2- and 4-year local control rates were 100 and 95.7%, respectively. Permanent trigeminal and facial nerve complications were 0 and 6%, respectively. The actuarial 2- and 3-year serviceable hearing preservation rates were both 63%. The median loss in speech reception threshold was 15 dB (range--10 to 65 dB). The radiotherapy dose to the cochlea was the only significant prognostic factor for hearing deterioration. Radiotherapy dose to the cochlear nucleus, patient age, sex, pre-FSRT hearing grade, tumor volume, and intracanalicular tumor volume failed to show any significance as prognostic factors. RESULTS Five cases were replanned with four different radiotherapy techniques (namely arcs, dynamic arcs, static conformal fields, and intensity-modulated radiotherapy), with the cochlea defined as an organ at risk. In all cases, replanning resulted in statistically significant reduction in radiation to the cochlea (p = 0.001); however, no single replanning technique was found to be superior. CONCLUSIONS The radiation dose to the cochlea is strongly predictive for subsequent hearing deterioration. It is essential for the cochlea to be outlined as an organ at risk, and for radiation techniques to be optimized, to improve long-term hearing preservation.

Stereotactic fractionated radiotherapy for cavernous venous malformations (hemangioma) of the orbit.

Purpose: To determine the safety and efficacy of the multiple postoperative applications of mitomycin-C (MMC) after endocanalicular laser dacryocystorhinostomy. Methods: Prospective interventional case series of 125 endocanalicular laser dacryocystorhinostomies using the diode laser. Mitomycin-C was placed intra-operatively in all cases. Application of MMC was also done postoperatively at 1 week, 2 weeks, and 3 weeks. The main outcome measure for success was resolution or improvement of epiphora, the patency of the osteum and the presence or absence of complications from the MMC application. Patients were followed up for at least 12 months. Results: A total of 125 consecutive endocanalicular laser dacryocystorhinostomies on 114 patients (102 women, 12 men, mean age 60 years) were done from January 2002 to January 2005. The success rate at 12 months postoperatively was 92.8%. All failures were due to cicatricial closure of the osteum. No significant intra-operative and postoperative nasal complications from the MMC were recorded. Conclusion: Multiple postoperative applications of MMC appears to be a safe and effective adjunctive modality after endocanalicular laser dacryocystorhinostomy in primary acquired nasolacrimal duct obstruction.PURPOSE Cavernous malformations (hemangioma) of the orbit, when symptomatic, can often be treated successfully with complete surgical excision. However, when they involve local structures in their capsule, are situated in the orbital apex, or extend through the superior orbital fissure, the risks of surgery increase significantly. In such cases, alternative treatment modalities can be explored. In this study, the authors report on the use of fractionated stereotactic radiotherapy (SFRT) for the treatment of surgically complicated cavernous malformations. METHODS In this retrospective cohort study, the authors reviewed the clinical and radiologic records of 5 patients treated with SFRT over the past 5 years. RESULTS Patients ranged in age from 30 to 65 years, and 3 out of 5 were female. Two cases involved the cavernous sinus, one involved the ophthalmic artery, one involved the posterior ciliary artery, and the last traversed the superior orbital fissure. Four had significant visual field defects. Each was treated with SFRT. A total dose of 4000 cGy divided into 20,200 cGy fractions was applied for 3 cases, while 2 other cases were treated with total doses of 4563 and 4959 cGy divided into 28 × 162 cGy and 29 × 171 cGy fractions, respectively. Rapid resolution of visual field defect was noted by 3 months, and overall tumor shrinkage was on average 60% (range: 32-79%). Follow-up was on average 23.4 months (range: 5-50 months). No complications of treatment were noted. CONCLUSIONS For symptomatic cavernous malformations demonstrating anatomical position that may increase risk of surgical excision, SFRT is an effective and safe method to control lesion size and improve visual function.

Long-Term Outcomes of Fractionated Stereotactic Radiation Therapy for Pituitary Adenomas at the BC Cancer Agency

PURPOSE To assess the long-term disease control and toxicity outcomes of fractionated stereotactic radiation therapy (FSRT) in patients with pituitary adenomas treated at the BC Cancer Agency. METHODS AND MATERIALS To ensure a minimum of 5 years of clinical follow-up, this study identified a cohort of 76 patients treated consecutively with FSRT between 1998 and 2007 for pituitary adenomas: 71% (54/76) had nonfunctioning and 29% (22/76) had functioning adenomas (15 adrenocorticotrophic hormone-secreting, 5 growth hormone-secreting, and 2 prolactin-secreting). Surgery was used before FSRT in 96% (73/76) of patients. A median isocenter dose of 50.4 Gy was delivered in 28 fractions, with 100% of the planning target volume covered by the 90% isodose. Patients were followed up clinically by endocrinologists, ophthalmologists, and radiation oncologists. Serial magnetic resonance imaging was used to assess tumor response. RESULTS With a median follow-up time of 6.8 years (range, 0.6 - 13.1 years), the 7-year progression-free survival was 97.1% and disease-specific survival was 100%. Of the 2 patients with tumor progression, both had disease control after salvage surgery. Of the 22 patients with functioning adenomas, 50% (11/22) had complete and 9% (2/22) had partial responses after FSRT. Of the patients with normal pituitary function at baseline, 48% (14/29) experienced 1 or more hormone deficiencies after FSRT. Although 79% (60/76) of optic chiasms were at least partially within the planning target volumes, no patient experienced radiation-induced optic neuropathy. No patient experienced radionecrosis. No secondary malignancy occurred during follow-up. CONCLUSION In this study of long-term follow-up of patients treated for pituitary adenomas, FSRT was safe and effective.

Reduced Risk of Compressive Optic Neuropathy Using Orbital Radiotherapy in Patients With Active Thyroid Eye Disease

PURPOSE To compare the risk of developing compressive optic neuropathy in patients with active thyroid eye disease (TED) treated with corticosteroids with or without orbital radiotherapy. DESIGN Retrospective single-center case-control study. METHODS The clinical charts of 351 patients with active TED who received corticosteroids with or without orbital radiotherapy between 1999 and 2010 were reviewed. Patients with compressive optic neuropathy at the time of presentation were excluded. Group 1 received corticosteroids only and Group 2 received corticosteroids as well as orbital radiotherapy. The primary outcome measure was the development of compressive optic neuropathy. Secondary outcome measures were changes in other parameters indicating the activity of TED, including soft tissue inflammation, diplopia, ocular motility restriction, and appearance. RESULTS There were 144 cases in Group 1 and 105 in Group 2. Both groups were matched for age, sex, and stability of thyroid function. The 2 groups differed only in the modality of treatment for active TED. The main indication for treatment in both groups was soft tissue inflammation. Corticosteroids were initiated an average of 2.6 months following symptom onset in Group 1 and 2.5 months in Group 2. Group 2 received orbital radiotherapy on average 4.2 months following the initiation of corticosteroid therapy and 8% (9/105) were intolerant to corticosteroids. At an average of 3.2 years follow-up, compressive optic neuropathy had developed in 17% (25/144) of Group 1 and 0% of Group 2 (P < .0001), on average 5.5 months following the initiation of corticosteroid therapy. Although both groups experienced a significant reduction in periocular inflammation, the radiotherapy-treated group demonstrated a significantly greater improvement in ocular motility. CONCLUSION The rate of compressive optic neuropathy was significantly lower and improvement in ocular motility greater in patients receiving orbital radiotherapy in addition to corticosteroids. Patients with active TED appear to have an effective and sustained response to orbital radiotherapy combined with corticosteroids that is protective against disease progression and the development of compressive optic neuropathy.

Outcomes of Proton Radiation Therapy for Peripapillary Choroidal Melanoma at the BC Cancer Agency

PURPOSE To report toxicity, local control, enucleation, and survival rates for patients with peripapillary choroidal melanoma treated with proton therapy in Canada. METHODS AND MATERIALS We performed a retrospective analysis of patients with peripapillary choroidal melanoma (≤ 2 mm from optic disc) treated between 1995 and 2007 at the only Canadian proton therapy facility. A prospective database was updated for follow-up information from a chart review. Descriptive and actuarial data are presented. RESULTS In total, 59 patients were treated. The median age was 59 years. According to the 2010 American Joint Committee on Cancer TNM classification, there were 20 T1 tumors (34%), 28 T2 tumors (48%), and 11 T3 tumors (19%). The median tumor diameter was 11.4 mm, and the median thickness was 3.5 mm. Median follow-up was 63 months. Nineteen patients received 54 cobalt gray equivalents (CGE) and forty patients received 60 CGE, each in 4 fractions. The 5-year actuarial local control rate was 91% (T1, 100%; T2, 93%; and T3, 59%) (p = 0.038). There was a suggestive relationship between local control and dose. The local control rate was 97% with 60 CGE and 83% with 54 CGE (p = 0.106). The metastasis-free survival rate was 82% and related to T stage (T1, 94%; T2, 84%; and T3, 47%) (p < 0.001). Twelve patients died, including eleven with metastases. The 5-year actuarial rate of neovascular glaucoma was 31% (23% for T1-T2 and 68% for T3, p < 0.001), and that of enucleation was 0% for T1, 14% for T2, and 72% for T3 (p < 0.001). Radiation retinopathy (74%) and optic neuropathy (64%) were common within-field effects. CONCLUSIONS Proton therapy provides excellent local control with acceptable toxicity while conserving the globe in 80% of cases. These results are consistent with other single-institution series using proton radiotherapy, and toxicity rates were acceptable. T3 tumors carry a higher rate of both local recurrence and metastasis.

The treatment of choroidal melanoma with 198Au plaque brachytherapy

BACKGROUND Seventy-nine consecutive patients with primary choroidal melanoma were treated with 198 Au plaque brachytherapy at the British Columbia Cancer Agency (BCCA) between 1992 and 1998 with perioperative ultrasound to confirm plaque placement. Seventy-seven of the 79 patients were analyzable for this study. RESULTS Five year actuarial disease specific survival, enucleation free survival, and local control are 95, 94, and 98%, respectively. There were four melanoma related deaths, all secondary to liver metastases. CONCLUSIONS The BCCA experience in selected patients with choroidal melanomas treated with 198Au plaque brachytherapy has resulted in excellent survival and local control with minimal significant toxicity while preserving the globe. Our results using 198 Au seeds are comparable to other series using 125I, 60Co, and 106Ru at other centers.

Optimization of Stereotactic Radiotherapy Treatment Delivery Technique for Base-Of-Skull Meningiomas

This study compares static conformal field (CF), intensity modulated radiotherapy (IMRT), and dynamic arcs (DA) for the stereotactic radiotherapy of base-of-skull meningiomas. Twenty-one cases of base-of-skull meningioma (median planning target volume [PTV] = 21.3 cm3) previously treated with stereotactic radiotherapy were replanned with each technique. The plans were compared for Radiation Therapy Oncology Group conformity index (CI) and homogeneity index (HI), and doses to normal structures at 6 dose values from 50.4 Gy to 5.6 Gy. The mean CI was 1.75 (CF), 1.75 (DA), and 1.66 (IMRT) (p < 0.05 when comparing IMRT to either CF or DA plans). The CI (IMRT) was inversely proportional to the size of the PTV (Spearmans rho = -0.53, p = 0.01) and at PTV sizes above 25 cm3, the CI (IMRT) was always superior to CI (DA) and CI (CF). At PTV sizes below 25 cm3, there was no significant difference in CI between each technique. There was no significant difference in HI between plans. The total volume of normal tissue receiving 50.4, 44.8, and 5.6 Gy was significantly lower when comparing IMRT to CF and DA plans (p < 0.05). There was significantly improved dose sparing for the brain stem and ipsilateral temporal lobe with IMRT but no significant difference for the optic chiasm or pituitary gland. These results demonstrate that stereotactic IMRT should be considered to treat base-of-skull meningiomas with a PTV larger than 25 cm3, due to improved conformity and normal tissue sparing, in particular for the brain stem and ipsilateral temporal lobe.

Chromosomal alterations in oligodendroglial tumours over multiple surgeries: is tumour progression associated with change in 1p/19q status?

Background Oligodendroglial neoplasms have morphologic and genotypic heterogeneity. Loss of heterozygosity (LOH) of 1p and/or 19q is associated with increased treatment responsiveness and overall survival. However, the pathogenesis of treatment-resistance is unknown. We sought to determine if tumour progression is due to a proliferating sub-population of tumour cells with intact 1p, or if recurrent tumours retain 1p/19q LOH. Methods 24 patients with oligodendroglial neoplasms, possessing biopsy samples taken at diagnosis and at progression, were identified. 53 tumour specimens were available for LOH analysis of 1p and 19q, using PCR amplification of multiple microsatellite markers. 40 were also tested for 9p and 10q. Results At diagnosis, the median age was 34 (24–66) years, 14 were male. 19 tumours were WHO Grade II, and 5 were high grade. The most common genomic status was 19q LOH (70%). 13 (54%) tumours were 1p LOH at diagnosis: of these, 12 were 19q LOH, and 1 was 19q uninformative. All 12 patients with 1p/19q LOH primary tumours had persistent co-deletion at progression. 9 (38%) tumours were 1p intact at diagnosis, and 8 remained 1p intact in the progressed tumours. There was little heterogeneity of 9p and 10q between tumours at diagnosis and progression. Conclusion 100% of oligodendroglial tumours with 1p/19q LOH, demonstrated persistent 1p/19q LOH in the progressed tumour. Therefore, progression of these tumours is not due to a proliferating sub-population of treatment-resistant, 1p intact tumour cells. We propose that additional mutations contribute to this aggressive phenotype, however, 9p LOH or 10q LOH are unlikely to be involved.