Walter J. Curran

Final report of a phase I/II trial of hyperfractionated and accelerated hyperfractionated radiation therapy with carmustine for adults with supratentorial malignant gliomas: Radiation therapy oncology group study 83-02

Efforts to improve local control and survival by increasing the dose of once‐daily radiation therapy beyond 70 Gray (Gy) for patients with malignant gliomas have as yet been unsuccessful. Hyperfractionated radiation therapy (HF) should allow for delivery of a higher total dose without increasing normal tissue late effects, whereas accelerated hyperfractionated radiation therapy (AHF) may minimize tumor repopulation by shortening overall treatment time. The Radiation Therapy Oncology Group (RTOG) conducted a randomized Phase I/II study of escalating doses of HF and AHF with carmustine (bis‐chloroethyl nitrosourea [BCNU]) for adults with supratentorial glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA). Primary study endpoints were overall survival and acute and chronic treatment‐related toxicity.

Preservation of Cranial Nerve Function after Treatment of Acoustic Neurinomas with Fractionated Stereotactic Radiotherapy

Twenty-seven acoustic tumors in 26 patients were treated with multiple fractionated linear-accelerator-based stereotactic radiotherapy (SRT). All patients with intact pretreatment facial nerve function with either small or large tumor volumes have thus far experienced no treatment-related facial neuropathy, including 9 patients with a mean follow-up of 22.4 +/- 1.6 months. The incidence of evaluable trigeminal neuropathy was 13%, and in 5 of 7 patients with serviceable pretreatment hearing, audiometry was unchanged in the immediate posttreatment period. Longer follow-up will be necessary to evaluate hearing preservation after SRT. Tumor response with central necrosis was seen in all assessable patients. SRT can be performed for cerebellopontine angle tumors with accuracy and reproducibility. It achieves a biological response similar to single fraction radiosurgery and may lower the incidence of facial and trigeminal neuropathies.

Multiple Fractionated Stereotactic Radiotherapy of Residual Pituitary Macroadenomas: Initial Experience

OBJECTIVE We describe our initial experience with fractionated stereotactic radiotherapy (SRT) for the treatment of 19 patients with secretory and nonsecretory pituitary macroadenomas. The primary endpoints of local control and the documentation of any MRI T2-weighted changes in contiguous brain tissues are discussed. METHODS Between 1/95 and 1/97, 19 patients were planned with the X-Knife 3-D planning system (Radionics, Burlington, Mass., USA) and received a median dose of 46 Gy in daily 2.0-Gy fractions. Treatments were delivered stereotactically with a dedicated 600SR linear accelerator (Varian Corporation, Palo Alto, Calif., USA). Immobilization was achieved with the Gill-Thomas-Cosman relocatable frame. The mean tumor size was 2.24 cm. The mean prescription isodose was 87%. The mean age was 53 years (10 male, 9 female). The mean follow-up time was 10 months (range 1-24 months). The mean optic chiasm and brain stem doses were calculated at 38 and 13 Gy, respectively. All patients were evaluated with pre- and postgadolinum-enhanced MRI scans and Humphrey visual field tests. RESULTS In the posttreatment period, local control (absence of tumor progression) has been achieved in all of the patients. The treatment was well tolerated in all patients. No acute complications, no visual changes and no T2-weighted MRI or proton density changes were documented in any of the 19 patients. CONCLUSION These preliminary results suggest that SRT compares favorably with conventional radiotherapy in achieving local control. The doses to the brainstem and the temporal lobes are significantly decreased and at early follow-up no white matter changes are seen on MRI after SRT. The true frequency of grade 1-4 changes are likely underestimated as similar changes often occur in association with tumor edema or after surgery. Given the uncertain neurocognitive significance of the white matter changes associated with treating these benign tumors by conventional radiotherapy, we are currently treating all pituitary adenomas with fractionated SRT to reduce the potential sequelae.

Stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of nonacoustic cranial nerve schwannomas.

OBJECTIVETo review outcomes after fractionated stereotactic radiotherapy (FSR) and stereotactic radiosurgery (SRS) for nonacoustic cranial nerve schwannomas. METHODSWe reviewed medical records of 39 patients who received FSR or SRS for nonacoustic cranial nerve schwannomas at our institution during the period from 1996 to 2007. RESULTSTumors involved Cranial Nerves V (n = 19), III (n = 2), VI (n = 3), VII (n = 5), IX (n = 2), X (n = 5), and XII (n = 2) and the cavernous sinus (n = 1). Irradiation was performed after partial resection, biopsy, or no previous surgery in 16, 2, and 21 patients, respectively. Twenty-four patients received FSR, delivered in 1.8- to 2.0-Gy fractions to a median dose of 50.4 Gy (range, 45.0–54.0 Gy). Fifteen patients received SRS to a median dose of 12.0 Gy (range, 12–15 Gy). Mild acute toxicity occurred in 23% of the patients. The 2-year actuarial tumor control rate after FSR and SRS was 95%. The median follow-up period was 24 months. Changes in cranial nerve deficits after stereotactic irradiation were analyzed for patients with follow-up periods greater than 12 months (n = 26); cranial nerve deficits improved in 50%, were stable in 46%, and worsened in 4% of the patients. No significant difference was observed for FSR compared with SRS with regard to local control or to improvement of cranial nerve-related symptoms (P = 0.17). CONCLUSIONSRS and FSR are both well-tolerated treatments for nonacoustic cranial nerve schwannomas, providing excellent tumor control and a high likelihood of symptomatic improvement.

A generalized film technique for the verification of vertex fields used in the treatment of brain tumors

With the availability of commercial three-dimensional (3D)-treatment planning systems, more and more treatment plans call for the use of noncoplanar conformal beams for the treatment of brain tumors. However, techniques for the verification of many noncoplaner beams, such as vertex fields which involve any combination of gantry, collimator, and table angles, do not exist. The purpose of this work is to report on the results of an algorithm and a technique that have been developed for the verification of noncoplanar vertex fields used in the treatment of brain tumors. This technique is applicable to any geometric orientation of the beam, i.e., a beam orientation that consists of any combination of gantry, table, and collimator rotations. The method consists of superimposing a central plane image of a correctly magnified vertex field on a lateral or oblique field port film. To achieve this, the 3D coordinates of the projection of the isocenter onto the film for lateral (or oblique) as well as the vertex fields are determined and then appropriately matched. Coordinate transformation equations have been developed that enable this matching precisely. A film holder has been designed such that a film cassette can be secured rigidly along the side rails of the treatment table. The technique for taking a patient treatment setup verification film consists of two steps. In the first step, the gantry, table, and collimator angles for the lateral (or oblique) field are set and the usual double exposures are made; the first exposure corresponds to that of the treatment portal with the isocenter clearly identified and the second one a larger radiation field so that the peripheral anatomy is visible on the film. In the next step, the gantry, table, and collimator angles are positioned for the vertex field and the table is moved laterally and vertically and the film longitudinally to a position that will enable precise matching of the isocenter on the film. A third exposure is then taken with the vertex portal. What is seen on the film is a superposition of a central plane image of the vertex field onto the image of the lateral or oblique field. This technique has been used on 60 patients treated with noncoplanar fields for brain tumors. In all of these cases, the coincidence of the projection of the isocenter for the lateral (or oblique) and the vertex fields was found to be within 3 mm.

40 Pretreatment hemoglobin level influences local control and survival of T1-T2 squamous cell carcinomas of the glottic larynx

PURPOSE A number of reports have documented the relationship between pretreatment hemoglobin level and local control and/or survival in the treatment of cervix, bladder, and advanced head and neck tumors. Consideration of correcting anemia before initiation of radiation therapy may prove increasingly important as clinical trials use intensive induction chemotherapy in the treatment of head and neck carcinomas. Neoadjuvant chemotherapy may produce anemia, which in turn may reduce the effectiveness of subsequent irradiation. MATERIALS AND METHODS One hundred nine patients with T1-2N0 squamous cell carcinoma of the glottic larynx were treated with definitive radiotherapy at the Fox Chase Cancer Center between June 1980 and November 1990. Follow-up times ranged from 26 to 165 months (median, 82). RESULTS The 2-year local control rate for patients who presented with a hemoglobin level < or = 13 g/dL was 66%, compared with 95% for patients with a hemoglobin level more than 13 g/dL (P = .0018). The 2-year survival rate for patients with a hemoglobin level < or = 13 g/dL was 46%, compared with 88% for patients with a hemoglobin level more than 13 g/dL (P < .001). Cox proportional hazards regression analysis showed that hemoglobin level (P = .0016) was the only variable that significantly influenced local control (P = .0016) and survival (P < .0001). CONCLUSION Patients who presented with hemoglobin levels more than 13 g/dL had significantly higher local control and survival rates. The strong apparent correlation between hemoglobin level, local control, and survival supports consideration of correcting anemia before initiation of radiation therapy.

Does size matter? Investigating the optimal planning target volume margin for postoperative stereotactic radiosurgery to resected brain metastases

OBJECTIVEThe optimal margin size in postoperative stereotactic radiosurgery (SRS) for brain metastases is unknown. Herein, the authors investigated the effect of SRS planning target volume (PTV) margin on local recurrence and symptomatic radiation necrosis postoperatively.METHODSRecords of patients who received postoperative LINAC-based SRS for brain metastases between 2006 and 2016 were reviewed and stratified based on PTV margin size (1.0 or > 1.0 mm). Patients were treated using frameless and framed SRS techniques, and both single-fraction and hypofractionated dosing were used based on lesion size. Kaplan-Meier and cumulative incidence models were used to estimate survival and intracranial outcomes, respectively. Multivariate analyses were also performed.RESULTSA total of 133 patients with 139 cavities were identified; 36 patients (27.1%) and 35 lesions (25.2%) were in the 1.0-mm group, and 97 patients (72.9%) and 104 lesions (74.8%) were in the > 1.0-mm group. Patient characteristics were balanced, except the 1.0-mm cohort had a better Eastern Cooperative Group Performance Status (grade 0: 36.1% vs 19.6%), higher mean number of brain metastases (1.75 vs 1.31), lower prescription isodose line (80% vs 95%), and lower median single fraction-equivalent dose (15.0 vs 17.5 Gy) (all p < 0.05). The median survival and follow-up for all patients were 15.6 months and 17.7 months, respectively. No significant difference in local recurrence was noted between the cohorts. An increased 1-year rate of symptomatic radionecrosis was seen in the larger margin group (20.9% vs 6.0%, p = 0.028). On multivariate analyses, margin size > 1.0 mm was associated with an increased risk for symptomatic radionecrosis (HR 3.07, 95% CI 1.13-8.34; p = 0.028), while multifraction SRS emerged as a protective factor for symptomatic radionecrosis (HR 0.13, 95% CI 0.02-0.76; p = 0.023).CONCLUSIONSExpanding the PTV margin beyond 1.0 mm is not associated with improved local recurrence but appears to increase the risk of symptomatic radionecrosis after postoperative SRS.