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Andrew E. H. Elia, Helen A. Shih and Jay S. Loeffler

✓Meningiomas are the second most common primary tumor of the brain. Gross-total resection remains the preferred treatment if achievable with minimal morbidity. For incompletely resected or inoperable benign meningiomas, 3D conformal external-beam radiation therapy can provide durable local tumor control in 90 to 95% of cases. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) are highly conformal techniques, using steep dose gradients and stereotactic patient immobilization. Stereotactic radiosurgery has been used as an alternative or adjuvant therapy to surgery for meningiomas in locations, such as the skull base, where operative manipulation may be particularly difficult. Stereotactic radiotherapy is useful for larger meningiomas (> 3–3.5 cm) and those closely approximating critical structures, such as the optic chiasm and brainstem. Although SRS has longer follow-up than SRT, both techniques have excellent 5-year tumor control rates of greater than 90% for benign meningiomas. Stereotactic radiotherapy has toxicity equivalent to that of radiosurgery, despite its biased use for larger meningiomas with more complicated volumes. Reported rates of imaging-documented regression are higher for radiosurgery, but neurological recovery is relatively good with both techniques. Stereotactic radiosurgery and fractionated SRT are complementary techniques appropriate for different clinical scenarios.

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Clark C. Chen, Paul Chapman, Joshua Petit and Jay Loeffler

Object

Photon energy deposition from gamma or photon sources follows the law of exponential decay. Consequently, energy is deposited over the entire path of the radiation beam, resulting in dose distribution before and after the target is reached. In contrast, the physical properties of protons are such that energy deposition occurs with no exit dose beyond the target volume. Therefore, relative to photons, proton beams represent a superior platform for the administration of radiosurgery.

Methods

In this review, the authors will discuss the fundamental principles underlying photon- and proton-based stereotactic radiosurgery (SRS). The clinical efficacy of proton-based SRS in the treatment of arteriovenous malformations, vestibular schwannomas, and pituitary adenomas is reviewed.

Results

Direct comparisons of clinical results attained using photon- and proton-based SRS are confounded by a bias toward reserving proton beams for the treatment of larger and more complex lesions. Despite this bias, the clinical outcomes for proton-based SRS have been excellent and have been at least comparable to those for photon-based treatments.

Conclusions

The physical properties of proton radiation offer superior conformality in dose distribution relative to photon irradiation. This advantage becomes more apparent as the lesion size increases and will probably be magnified with the development of intensity-modulated proton techniques.

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Douglas Kondziolka, L. Dade Lunsford, Jay S. Loeffler and William A. Friedman

Object. Radiosurgery and radiation therapy represent important but unique treatment paradigms for patients with certain neoplasms, vascular lesions, or functional disorders. The authors discuss their differences.

Methods. Reviewing the authors' experiences shows how the roles of these approaches vary just as their techniques differ. The distinct differences include the method of target localization (intraoperative compared with pretreatment) and irradiation (focused compared with wide-field), their radiobiology (effects of a single high-dose compared with multiple fractions), the physicians and other health personnel involved in the conduct of these procedures (surgical team compared with radiation team), and the expectations that follow treatment. During the last decade, considerable confusion has grown regarding nomenclature, requisite physician training, and the roles of the physician and surgeon. Ten years ago, two task forces on radiosurgery were created by national organizations in neurosurgery and radiation oncology to address these issues of procedural conduct and quality-assurance requirements. At the present time these guidelines are widely ignored. Currently, many patients, payers, and regulatory agencies are bewildered. What are the differences among stereotactic radiosurgery, fractionated radiation therapy, and stereotactic radiation therapy? Radiosurgery is to radiation therapy as microsurgery is to “microtherapy.”

Conclusions. In this report the authors discuss terminology, training, and physician roles in this expanding field.

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L. Dade Lunsford

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Michael Schulder, Jay S. Loeffler, Anthony E. Howes, Eben Alexander III and Peter McL. Black

✓ Harvey Cushing performed over 2000 operations on patients with brain tumors, including 832 for gliomas. He implanted radioactive radium needles, known as a “radium bomb,” in a small number of these patients. He was not impressed with the results and did not pursue this method of treatment in a serious way. The authors present here Cushing's little-known experience with brachytherapy and discuss the reasons for his lack of interest in this technique, despite his advocacy of radiotherapy for certain lesions. An interesting perspective is offered for contemporary neurosurgeons involved in the treatment of brain tumors with cranial irradiation.

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William T. Curry Jr., Garth Rees Cosgrove, Fred H. Hochberg, Jay Loeffler and Nicholas T. Zervas

Object. The Photon Radiosurgery System (PRS) is a miniature x-ray generator that can stereotactically irradiate intracranial tumors by using low-energy photons. Treatment with the PRS typically occurs in conjunction with stereotactic biopsy, thereby providing diagnosis and treatment in one procedure. The authors review the treatment of patients with brain metastases with the aid of the PRS and discuss the indications, advantages, and limitations of this technique.

Methods. Clinical characteristics, treatment parameters, neuroimaging-confirmed outcome, and survival were reviewed in all patients with histologically verified brain metastases who were treated with the PRS at the Massachusetts General Hospital between December 1992 and November 2000. Local control of lesions was defined as either stabilization or diminution in the size of the treated tumor as confirmed by Gd-enhanced magnetic resonance imaging.

Between December 1992 and November 2000, 72 intracranial metastatic lesions in 60 patients were treated with the PRS. Primary tumors included lung (33 patients), melanoma (15 patients), renal cell (five patients), breast (two patients), esophageal (two patients), colon (one patient), and Merkle cell (one patient) cancers, and malignant fibrous histiocytoma (one patient). Supratentorial metastases were distributed throughout the cerebrum, with only one cerebellar metastasis. The lesions ranged in diameter from 6 to 40 mm and were treated with a minimal peripheral dose of 16 Gy (range 10–20 Gy). At the last follow-up examination (median 6 months), local disease control had been achieved in 48 (81%) of 59 tumors. An actuarial analysis demonstrated that the survival rates at 6 and 12 months were 63 and 34%, respectively. Patients with a single brain metastasis survived a mean of 11 months. Complications included four patients with postoperative seizures, three with symptomatic cerebral edema, two with hemorrhagic events, and three with symptomatic radiation necrosis requiring surgery.

Conclusions. Stereotactic interstitial radiosurgery performed using the PRS can obtain local control of cerebral metastases at rates that are comparable to those achieved through open resection and external stereotactic radiosurgery. The major advantage of using the PRS is that effective treatment can be accomplished at the time of stereotactic biopsy.

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Paulo A. Carvalho, Richard B. Schwartz, Eben Alexander III, Basem M. Garada, Robert E. Zimmerman, Jay S. Loeffler and B. Leonard Holman

✓ Deteriorating clinical status after high-dose radiation therapy for high-grade gliomas may be due to radiation changes or may signal recurrent or residual tumor mass. The two conditions cannot be distinguished reliably by computerized tomography (CT) or magnetic resonance (MR) imaging. The authors assessed the ability of sequential thallium-201 chloride (201T1) and technetium-99m hexamethylpropylene amine oxime (99mTc HMPAO) single-photon emission CT (SPECT) to distinguish tumor recurrence from radiation changes after high-dose (≥ 600 cGy) radiation therapy for malignant gliomas. Preoperative tumor/nontumor uptake ratios were analyzed in 32 patients and correlated with the presence of gross tumor at the time of reoperation.

In 12 of 13 patients with 201T1 tumor/scalp ratios of 3.5 or greater, recurrent tumor was present. The authors found 99mTc HMPAO SPECT to be useful for identifying the absence of solid tumor recurrence in patients with low to moderate 201T1 uptake (ratio 1.1 to 3.4) and low perfusion to that site. In 11 of 12 patients with 99mTc HMPAO tumor/cerebellum ratios of 0.50 or less, no recurrent tumor mass was present. Three of seven patients with 201T1 ratios of 3.4 or less and 99mTc HMPAO ratios of 0.51 or more had recurrent tumor found at surgery; thus the test was not predictive in this group. It is concluded that the use of sequential 201T1 and 99mTc HMPAO SPECT accurately identifies the presence of tumor recurrence versus radiation changes in most patients with high-grade astrocytomas who have undergone tumor resection and high-dose radiation therapy.

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Jack P. Rock, Stephen Haines, Lawrence Recht, Mark Bernstein, Raymond Sawaya, Tom Mikkelsen and Jay Loeffler

Object

In January 1998 the Guidelines and Outcomes Committee of the American Association of Neurological Surgeons (AANS) issued a charge for the development of evidence-based practice parameters focusing on the treatment of patients with single metastasis to the brain. The charge was imposed in response to the significant controversy surrounding questions relating to the optimal management strategies for patients with single brain metastasis.

Methods

A team consisting of physicians from the AANS, the American Academy of Neurology, and the American Association of Therapeutic Radiation Oncology convened and the literature was reviewed. Methodically drawing from the best of Class I, II, and III levels of available evidence, authors sought to determine how the literature addressed and disposed of the question of the optimal management for an adult with a known history of cancer and a single meta-static brain lesion. Framing the question in this specific manner allowed researchers to focus directly on treatment issues, without having to consider diagnostic issues.

Conclusions

The results of the evidence-based analysis demonstrated that there was insufficient information to establish standards of care. Data from the literature does, however, support a guideline stating that surgical resection accompanied by whole brain radiation therapy is associated with the best survival rate. Additional lower-quality evidence supports an option for management with radiosurgery.

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Dennis C. Shrieve, Eben Alexander III, Peter McL. Black, Patrick Y. Wen, Howard A. Fine, Hanne M. Kooy and Jay S. Loeffler

Object. To assess the value of stereotactic radiosurgery (SRS) as adjunct therapy in patients suffering from glioblastoma multiforme (GBM), the authors analyzed their experience with 78 patients.

Methods. Between June 1988 and January 1995, 78 patients underwent SRS as part of their initial treatment for GBM. All patients had undergone initial surgery or biopsy confirming the diagnosis of GBM and received conventional external beam radiotherapy. Stereotactic radiosurgery was performed using a dedicated 6-MV stereotactic linear accelerator. Thirteen patients were alive at the time of analysis with a median follow-up period of 40.8 months. The median length of actuarial survival for all patients was 19.9 months. Twelve- and 24-month survival rates were 88.5% and 35.9%, respectively. Patient age and Radiation Therapy Oncology Group (RTOG) class were significant prognostic indicators according to univariate analysis (p < 0.05). Twenty-three patients aged younger than 40 years had a median survival time of 48.6 months compared with 55 older patients who had 18.2 months (p < 0.001). Patients in this series fell into RTOG Classes III (27 patients), IV (29 patients), or V (22 patients). Class III patients had a median survival time of 29.5 months following diagnosis; this was significantly longer than median survival times for Classes IV and V, which were 19.2 and 18.2 months, respectively (p = 0.001). Only patient age (< 40 years) was a significant prognostic factor according to multivariate analysis. Acute complications were unusual and limited to exacerbation of existing symptoms. There were no new neuropathies secondary to SRS. Thirty-nine patients (50%) underwent reoperation for symptomatic necrosis or recurrent tumor. The rate of reoperation at 24 months following SRS was 54.8%.

Conclusions. The addition of a radiosurgery boost appears to confer a survival advantage to selected patients.