Dennis C. Shrieve

Comparison of Stereotactic Radiosurgery and Brachytherapy in the Treatment of Recurrent Glioblastoma Multiforme

ABSTRACTTHE PURPOSE OF this study was to compare the efficacy of stereotactic radiosurgery (SRS) and brachytherapy in the treatment of recurrent glioblastoma multiforme (GBM). The patients had either progressive GBM or pathologically proven GBM at recurrence after previous treatment for a lower grad

Initial clinical results of LINAC-based stereotactic radiosurgery and stereotactic radiotherapy for pituitary adenomas.

PURPOSEnTo retrospectively evaluate the initial clinical results of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) for pituitary adenomas with regard to tumor and hormonal control and adverse effects of the treatment.nnnSUBJECTS AND METHODSnForty-eight patients with pituitary adenoma who underwent SRS or SRT between September 1989 and September 1995 were analyzed. Of these, 18 received SRS and 30 received SRT. The median tumor volumes were 1.9 cm3 for SRS and 5.7 cm3 for SRT. Eleven of the SRS and 18 of the SRT patients were hormonally active at the time of the initial diagnosis. Four of the SRS and none of the SRT patients had a history of prior radiation therapy. Both SRS and SRT were performed using a dedicated stereotactic 6-MV linear accelerator (LINAC). The dose and normalization used for the SRS varied from 1000 cGy at 85% of the isodose line to 1500 cGy at 65% of the isodose line. For SRT patients, a total dose of 4500 cGy at 90% or 95% of the isodose line was delivered in 25 fractions of 180 cGy daily doses.nnnRESULTSnDisease control-The three year tumor control rate was 91.1% (100% for SRS and 85.3% for SRT). Normalization of the hormonal abnormality was achieved in 47% of the 48 patients (33% for SRS and 54% for SRT). The average time required for normalization was 8.5 months for SRS and 18 months for SRT. Adverse effects-The 3-year rate of freedom from central nervous system adverse effects was 89.7% (72.2% for SRS and 100% for SRT). Three patients who received SRS for a tumor in the cavernous sinus developed a ring enhancement in the temporal lobe as shown by follow-up magnetic resonance imaging. Two of these cases were irreversible and were considered to be radiation necrosis. None of the 48 patients developed new neurocognitive or visual disorders attributable to the irradiation. The incidence of endocrinological adverse effects were similar in the two groups, resulting in 3-year rates of freedom from newly initiated hormonal replacement of 78.4% (77.1% for SRS and 79.9% for SRT).nnnCONCLUSIONnConsidering the relatively high incidence of morbidity observed in the SRS group, we recommend SRT as the primary method of radiation therapy for pituitary tumors. When treating a lesion in the cavernous sinus with SRS, special attention should be paid to dose distribution in the adjacent brain parenchyma. Longer follow-up is necessary before drawing any conclusions about the advantages of these techniques over conventional external beam radiation therapy.

Fractionated stereotactic radiotherapy for the treatment of acoustic neuromas: preliminary results.

PURPOSEnTo evaluate the efficacy and toxicity of fractionated, stereotactic radiotherapy (SRT) for acoustic neuromas.nnnMETHODS AND MATERIALSnTwelve patients with acoustic neuroma were treated with SRT between June 1992 and October 1994. Follow-up ranged from 16-44 months. Patient age ranged from 27-70 (median: 45). Eight patients were treated with primary SRT and four patients were treated after primary surgical intervention for recurrent [3] or persistent [1] disease. Tumor volumes were 1.2-18.4 cm3 (median: 10.1 cm3). Collimator sizes ranged from 30-50 mm (median: 37.5). Tumors received 1.8 Gy/day normalized to the 95% isodose line. Patients received a minimum prescribed dose of 54 Gy in 27-30 fractions over a 6-week period.nnnRESULTSnAfter a median follow-up of 26.5 months, local control was obtained in 12 out of 12 lesions. Tumor regression was noted in three patients, and tumor stabilization was found in the remaining nine patients. No patient developed a new cranial nerve deficit. One patients developed worsening of preexisting Vth cranial neuropathy and another experienced a decrease in hearing. However, all nine patients with useful hearing prior to SRT maintained useful hearing at last follow-up.nnnCONCLUSIONSnStereotactic radiotherapy provided excellent local control without new cranial nerve deficits. These results must be viewed as tentative in nature because of the small number of patients and the short median follow-up period.

Radiosurgery for hemangioblastoma : Results of a multiinstitutional experience

PURPOSEnBetween June 1988 and June 1994. 38 hemangioblastomas were treated with stereotactic radiosurgery (SR) at three SR centers to evaluate the efficacy and potential toxicity of this therapeutic modality as an adjuvant or alternative treatment to surgical resection.nnnMETHODS AND MATERIALSnSR was performed using either a 201-cobalt source unit or a dedicated SR linear accelerator. Of the 18 primary tumors treated, 16 had no prior history of surgical resection and were treated definitively with SR and two primary lesions were subtotally resected and subsequently treated with SR. Twenty lesions were treated with SR after prior surgical failure (17 tumors) or failure after prior surgery and conventional radiotherapy (three tumors). Eight patients were treated with SR for multifocal disease (total, 24 known tumors). SR tumor volumes measured 0.05 to 12 cc (median: 0.97 cc). Minimum tumor doses ranged from 12 to 20 Gy (median: 15.5 Gy).nnnRESULTSnMedian follow-up from the time of SR was 24.5 months (range: 6-77 months). The 2-year actuarial over-all survival was 88 +/- 15% (95% confidence interval). Two-year actuarial freedom from progression was 86 +/- 12% (95% confidence interval). The median tumor volume of the lesions that failed to be controlled by SR was 7.85 cc (range: 3.20-10.53 cc) compared to 0.67 cc (range: 0.05-12 cc) for controlled lesions (p - 0.0023). The lesions that failed to be controlled by SR received a median minimum tumor dose of 14 Gy (range: 13-17 Gy) compared to 16 Gy (range: 12-20 Gy) for controlled lesions (p = 0.0239). Seventy-eight percent of the surviving patients remained neurologically stable or clinically improved. There were no significant permanent complications directly attributable to SR.nnnCONCLUSIONSnThis report documents the largest experience in the literature of the use of SR in the treatment of hemangioblastoma. We conclude that SR: (a) controls the majority of primary and recurrent hemangioblastomas; (b) offers the ability to treat multiple lesions in a single treatment session, which is particularly important for patients with Von Hippel-Lindau Syndrome; and that (c) better control rates are associated with higher doses and smaller tumor volumes.

Childhood optic chiasm gliomas: Radiographic response following radiotherapy and long-term clinical outcome

PURPOSEnIn children with chiasmal gliomas, radiation therapy can arrest progressive visual and neurologic impairment. We examined the radiographic response and clinical outcomes after irradiation.nnnMETHODS AND MATERIALSnForty-two children (median age at diagnosis, 6.6 years) with chiasmal gliomas were managed as follows: 11 asymptomatic patients with neurofibromatosis-1 (NF-1) were observed only; 2 patients, less than 3 years old, underwent surgery and chemotherapy to delay irradiation; and 29 patients with progressive disease received radiation with or without prior surgery or chemotherapy. Time to radiographic response, long-term tumor control and late sequelae were reviewed for the 29 irradiated patients.nnnRESULTSnThe probability of at least 50% radiographic response at 24 months after irradiation was 18.1% and increased to 38.2% by 48 months and 45.9% by 60 months. By actuarial analysis, the median time for such radiographic response was 62 months. For the 29 irradiated patients, the 10-year freedom from progression and overall survival rates were 100% and 89%, respectively (median follow-up for surviving patients, 108 months). Stabilization or improvement in vision occurred in 81% of 26 evaluable irradiated patients.nnnCONCLUSIONSnNotable radiographic response may be observed years after irradiation. Radiation therapy provides excellent long-term tumor control and vision preservation or improvement in the majority of patients with progressive chiasmal gliomas.

Results of Radiosurgery in the Management of Recurrent and Residual Medulloblastoma

Between June 1989 and January 1994, 14 patients with recurrent (n = 11) or posttreatment residual (n = 3) medulloblastoma were enrolled in a program to evaluate the efficacy and toxicity of stereotactic radiosurgery (SR). Initial treatment consisted of subtotal surgical resection in 12 patients and complete surgical resection in 2. Thirteen patients received systemic chemotherapy, and all had craniospinal irradiation prior to SR. SR was used as a technique for boosting sites of posttreatment residual disease in 3 patients (3 tumors) and as salvage therapy in 11 patients (14 tumors) with radiographically well-defined, discrete recurrent tumors. Patients underwent SR 1-97 (median 20) months after completing craniospinal irradiation. The median minimum peripheral tumor dose was 12 Gy. The median tumor volume at the time of SR was 6.9 cm3. With a median follow-up period from diagnosis of 27 (range 8-39) months, all patients treated with SR as a boost to sites of residual disease are alive without evidence of disease. In contrast, 6 of 11 patients who underwent SR for treatment of recurrent disease have died of progressive medulloblastoma. The median survival from the time of SR for patients treated for recurrent disease was 10 (range 5-59+) months. The predominant site of failure after SR was distant within the central nervous system, with 6 patients (43%) failing outside the posterior fossa. No patient failed locally within the radiosurgical target volume. Two patients (14%) developed marginal recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)

Permanent low-activity iodine-125 implants for cerebral metastases.

Beginning in 1987, selected patients with metastatic braintumors were treated with permanent implants of low-activityradioactive iodine-125 (125I) seeds. These patients underwent craniotomy,gross total resection of the metastatic lesion, andplacement of the seeds. In general, criteria fortreatment included the presence of a recurrent tumorwith a volume too large to permit radiosurgery,and a Karnofsky Performance Score of 70 orhigher. Thirteen patients underwent 14 implant procedures; allreceived external whole-brain radiotherapy. Implant dose ranged from43 Gy to 132 Gy, with a meanof 83 Gy. Survival after implantation ranged from2 weeks to almost 9 years, with amedian of 9 months. Clinical and radiographic localcontrol was obtained in 9 patients. Two patientsdied of acute, postoperative complications within a monthof implantation, so no information regarding tumor controlis available for them. Late complications included abone flap infection in one patient and aCSF leak in another; both were treated withoutfurther sequelae.These results demonstrate that permanent 125I implants canresult in good survival and quality of life,and occasionally can yield long-term survival. Potentially, itis a cost-effective treatment in that a separateprocedure for stereotactic implantation or radiosurgery is notneeded, as is the case with the useof temporary high-activity seeds. The permanent implantation itselfadds less than 10 minutes to the craniotomy,and the risk of symptomatic radiation necrosis islow. We recommend consideration of this procedure inpatients harboring large, recurrent metastatic tumors that requirefurther surgery.

Stereotactic Radiotherapy: A Technique for Dose Optimization and Escalation for Intracranial Tumors

Stereotactic radiosurgery offers the ability to treat relatively small volume intracranial lesions with single fraction, high dose radiotherapy while sparing surrounding tissue due to rapid fall off of dose outside of the treatment volume. Conventional radiotherapy takes advantage of the sparing effects of dose fractionation, but includes relatively large amounts of normal brain in the treatment volume the tolerance of which is dose-limiting. For some intracranial lesions it may not be optimal to treat with large single fractions due to tumor location or size. Conventional fractionated radiotherapy may not be optimum in all cases due to the necessary inclusion of normal structures. Through the development of relocatable head frames, the precision of stereotactic techniques and the biologic advantages of fractionation may be combined in stereotactic radiotherapy (SRT). We report on the treatment of 68 patients with intracranial lesions using a dedicated stereotactic linear accelerator to deliver SRT between June 1992 and June 1993. SRT was used either in order to optimize dose distribution and spare normal tissues in patients with excellent prognosis or in order to increase the dose to tumor while keeping doses to normal tissues below tolerance levels in patients with poorer prognosis (dose escalation). Histologies treated included meningioma, low grade astrocytoma, pituitary adenoma and acoustic neuroma. The most common treatment sites were the parasellar region and cavernous sinuses. Most patients (79%) had surgical debulking prior to SRT. 10-12 patients were treated daily. Patient positioning using relocatable stereotactic frames was highly precise. Acute and subacute side effects were minimal and radiographic responses have been similar to those expected with conventional radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Beam shaping for conformal fractionated stereotactic radiotherapy : A modeling study

PURPOSEnThe patient population treated with fractionated stereotactic radiotherapy (SRT) is significantly different than that treated with stereotactic radiosurgery (SRS). Generally, lesions treated with SRT are larger, less spherical, and located within critical regions of the central nervous system; hence, they offer new challenges to the treatment planner. Here a simple, cost effective, beam shaping system has been evaluated relative to both circular collimators and an ideal dynamically conforming system for effectiveness in providing conformal therapy for these lesions.nnnMETHODS AND MATERIALSnWe have modeled a simple system for conformal arc therapy using four independent jaws. The jaw positions and collimator angle are changed between arcs but held fixed for the duration of each arc. Eleven previously treated SRT cases have been replanned using this system. The rectangular jaw plans were then compared to the original treatment plans which used circular collimators. The plans were evaluated with respect to tissue sparing at 100%, 80%, 50%, and 20% of the prescription dose. A plan was also done for each tumor in which the beam aperture was continuously conformed to the beams eye view projection of the tumor. This was used as an ideal standard for conformal therapy in the absence of fluence modulation.nnnRESULTSnFor tumors with a maximum extent of over 3.5 cm the rectangular jaw plans reduced the mean volume of healthy tissue involved at the prescription dose by 57% relative to the circular collimator plans. The ideal conformal plans offered no significant further improvement at the prescription dose. The relative advantage of the rectangular jaw plans decreased at lower isodoses so that at 20% of the prescription dose tissue involvement for the rectangular jaw plans was equivalent to that for the circular collimator plans. At these isodoses the ideal conformal plans gave substantially better tissue sparing.nnnCONCLUSIONnA simple and economical field shaping device has been shown to provide all of the beam shaping advantage of a hypothetical ideal dynamically conforming system at the prescription level. This system may be immediately implemented in the clinic. It offers a substantial advantage over the currently used circular collimators in the high dose region with equivalent performance in the low dose region.

Further evidence for the absence of a hypoxic fraction in the 9L rat tumour multicellular spheroid system

The 9L gliosarcoma is an N-methylnitrosourea-induced rat brain tumour that has served as a predictive model for the efficacy of various chemotherapeutic agents against human brain tumours (Barker et al, 1973). Because it is one of two known animal tumour models that has no hypoxic fraction the 9L model is of questionable value for the study of the radiobiology of hypoxic cell sensitizers (Denekamp, 1980). Radiation survival curves of the intracerebral 9L (50 mg) and larger (30–2000 mg) subcutaneous 9L rat tumours do not have the “tail” that is normally associated with the presence of a hypoxic fraction (Leith et al, 1975; Wallen et al, 1980), and radiation survival curves of 9L multicellular spheroids that vary in size from small cell clusters to large spheroids, with diameters greater than 900 μm, show no tail (Deen et al, 1980). It may be that the hypoxic tail on the radiation survival curve found for other spheroid systems is, by itself, an unreliable index of the state of spheroid cell oxygenation (Du...