Barbara-Ann Millar

Fractionated stereotactic radiotherapy for acoustic neuroma: single-institution experience at The Princess Margaret Hospital.

The clinical outcome and toxicity of fractionated stereotactic radiotherapy (FSRT) was assessed for acoustic neuroma in 60 patients treated in a single institution.

Localized Orbital Mucosa-Associated Lymphoma Tissue Lymphoma Managed With Primary Radiation Therapy: Efficacy and Toxicity

PURPOSE To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). METHODS AND MATERIALS From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients. RESULTS The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade ≥2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). CONCLUSIONS POML responds favorably to moderate doses of RT but results in significant late morbidity. The majority of late effects were successfully managed. Lens shielding reduced the risk of cataracts and other late sequelae.

Impact of Immobilization on Intrafraction Motion for Spine Stereotactic Body Radiotherapy Using Cone Beam Computed Tomography

PURPOSE Spine stereotactic body radiotherapy (SBRT) involves tight planning margins and steep dose gradients to the surrounding organs at risk (OAR). This study aimed to assess intrafraction motion using cone beam computed tomography (CBCT) for spine SBRT patients treated using three immobilization devices. METHODS AND MATERIALS Setup accuracy using CBCT was retrospectively analyzed for 102 treated spinal metastases in 84 patients. Thoracic and lumbar spine patients were immobilized with either an evacuated cushion (EC, n = 24) or a semirigid vacuum body fixation (BF, n = 60). For cases treated at cervical/upper thoracic (thoracic [T]1-T3) vertebrae, a thermoplastic S-frame (SF) mask (n = 18) was used. Patient setup was corrected by using bony anatomy image registration and couch translations only (no rotation corrections) with shifts confirmed on verification CBCTs. Repeat imaging was performed mid- and post-treatment. Patient translational and rotational positioning data were recorded to calculate means, standard deviations (SD), and corresponding margins ± 2 SD for residual setup errors and intrafraction motion. RESULTS A total of 355 localizations, 333 verifications, and 248 mid- and 280 post-treatment CBCTs were analyzed. Residual translations and rotations after couch corrections (verification scans) were similar for all immobilization systems, with SDs of 0.6 to 0.9 mm in any direction and 0.9° to 1.6°, respectively. Margins to encompass residual setup errors after couch corrections were within 2 mm. Including intrafraction motion, as measured on post-treatment CBCTs, SDs for total setup error in the left-right, cranial-caudal, and anterior-posterior directions were 1.3, 1.2, and 1.0 mm for EC; 0.9, 0.7, and 0.9 mm for BF; and 1.3, 0.9, and 1.1 mm for SF, respectively. The calculated margins required to encompass total setup error increased to 3 mm for EC and SF and remained within 2 mm for BF. CONCLUSION Following image guidance, residual setup errors for spine SBRT were similar across three immobilization systems. The BF device resulted in the least amount of intrafraction motion, and based on this device, we justify a 2-mm margin for the planning OAR and target volume.

Long-term neurocognitive outcomes in young adult survivors of childhood acute lymphoblastic leukemia.

Five-year survival rates of childhood acute lymphoblastic leukemia (ALL) exceed 80% due to central nervous system-directed treatment including cranial radiation (CRT) and chemotherapy. However, these treatments are associated with neurocognitive compromise, the extent of which is correlated with higher dose and younger age at treatment. The aims of this study were to explore long-term neurocognitive outcomes in adult survivors of childhood ALL, and to identify measures sensitive to neurotoxicity in long-term survivors. We examined 24 adults who received 18 Gy CRT and chemotherapy for treatment of ALL between ages 2 and 15 years (median, 5.5). Time since diagnosis ranged from 6 to 26 years (median, 16.6). Younger age at diagnosis and longer time since diagnosis were associated with lower scores on a computerized battery that requires speed and accuracy across a number of domains (MicroCog), and other standardized neurocognitive tests. When compared with population norms, MicroCog indices were below average in survivors diagnosed with ALL before age 5, but only the reasoning/calculation index was below average in survivors diagnosed with ALL after age 5. In contrast, intelligence quotient (IQ) scores were average. In addition to confirming earlier studies showing that younger children are more vulnerable to treatment-related neurotoxicity, here we show that deficits exist many years post treatment even with a relatively lower dose of CRT, and that these deficits are especially evident on tasks involving rapid processing of information.

Image-guided, intensity-modulated radiation therapy (IG-IMRT) for skull base chordoma and chondrosarcoma: preliminary outcomes

BACKGROUND We report our preliminary outcomes following high-dose image-guided intensity modulated radiotherapy (IG-IMRT) for skull base chordoma and chondrosarcoma. METHODS Forty-two consecutive IG-IMRT patients, with either skull base chordoma (n = 24) or chondrosarcoma (n = 18) treated between August 2001 and December 2012 were reviewed. The median follow-up was 36 months (range, 3-90 mo) in the chordoma cohort, and 67 months (range, 15-125) in the chondrosarcoma cohort. Initial surgery included biopsy (7% of patients), subtotal resection (57% of patients), and gross total resection (36% of patients). The median IG-IMRT total doses in the chondrosarcoma and chordoma cohorts were 70 Gy and 76 Gy, respectively, delivered with 2 Gy/fraction. RESULTS For the chordoma and chondrosarcoma cohorts, the 5-year overall survival and local control rates were 85.6% and 65.3%, and 87.8% and 88.1%, respectively. In total, 10 patients progressed locally: 8 were chordoma patients and 2 chondrosarcoma patients. Both chondrosarcoma failures were in higher-grade tumors (grades 2 and 3). None of the 8 patients with grade 1 chondrosarcoma failed, with a median follow-up of 77 months (range, 34-125). There were 8 radiation-induced late effects-the most significant was a radiation-induced secondary malignancy occurring 6.7 years following IG-IMRT. Gross total resection and age were predictors of local control in the chordoma and chondrosarcoma patients, respectively. CONCLUSIONS We report favorable survival, local control and adverse event rates following high dose IG-IMRT. Further follow-up is needed to confirm long-term efficacy.

Predicting nonauditory adverse radiation effects following radiosurgery for vestibular schwannoma: a volume and dosimetric analysis.

PURPOSE To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. METHODS We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; and trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. RESULTS Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. CONCLUSIONS Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.

Salvage radiosurgery for brain metastases: Prognostic factors to consider in patient selection

PURPOSE Stereotactic radiosurgery (SRS) is offered to patients for recurrent brain metastases after prior brain radiation therapy (RT), but few studies have evaluated the efficacy of salvage SRS or factors to consider in selecting patients for this treatment. This study reports overall survival (OS), intracranial progression-free survival (PFS), and local control (LC) after salvage SRS, and factors associated with outcomes. METHODS AND MATERIALS This is a retrospective review of patients treated from 2009 to 2011 with salvage SRS after prior brain RT for brain metastases. Survival from salvage SRS and from initial brain metastases diagnosis (IBMD) was calculated. Univariate and multivariable (MVA) analyses included age, performance status, recursive partitioning analysis (RPA) class, extracranial disease control, and time from initial RT to salvage SRS. RESULTS There were 106 patients included in the analysis with a median age of 56.9 years (range 32.5-82 years). A median of 2 metastases were treated per patient (range, 1-12) with a median dose of 21 Gy (range, 12-24) prescribed to the 50% isodose. With a median follow-up of 10.5 months (range, 0.1-68.2), LC was 82.8%, 60.1%, and 46.8% at 6 months, 1 year, and 3 years, respectively. Median PFS was 6.2 months (95% confidence interval [CI]=4.9-7.6). Median OS was 11.7 months (95% CI=8.1-13) from salvage SRS, and 22.1 months from IBMD (95% CI=18.4-26.8). On MVA, age (P=.01; hazard ratio [HR]=1.04; 95% CI=1.01-1.07), extracranial disease control (P=.004; HR=0.46; 95% CI=0.27-0.78), and interval from initial RT to salvage SRS of at least 265 days (P=.001; HR=2.46; 95% CI=1.47-4.09) were predictive of OS. CONCLUSIONS This study demonstrates that patients can have durable local control and survival after salvage SRS for recurrent brain metastases. In particular, younger patients with controlled extracranial disease and a durable response to initial brain RT are likely to benefit from salvage SRS.

Volume specific response criteria for brain metastases following salvage stereotactic radiosurgery and associated predictors of response

Abstract Background. We aimed to derive three-dimensional volume-based (V3D) 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). Material and methods. 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 V3D using ITK-SNAP image segmentation software. Results. The median tumour diameter was 1.2 cm (range, 0.2–4.5 cm) and V3D was 0.73 cm3 (range, 0.01–22.7 cm3). The V3D 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 V3D >6.0 cm3 (p =0.043) predicted for local failure, and a baseline cumulative V3D of >3.0 cm3 (p =0.02) was adversely prognostic for survival. Conclusions. We define 3D volume specific criteria to base response upon for brain metastases treated with salvage SRS. Tumours with a V3D of greater than 6 cm3 are at a higher risk of local failure.

Breast cancer detection among young survivors of pediatric Hodgkin lymphoma with screening magnetic resonance imaging

Female survivors of pediatric Hodgkin lymphoma (HL) who have received chest radiotherapy are at increased risk of breast cancer. Guidelines for early breast cancer screening among these survivors are based on little data regarding clinical outcomes. This study reports outcomes of breast cancer screening with MRI and mammography (MMG) after childhood HL.

Upfront observation versus radiation for adult pilocytic astrocytoma

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.