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L Dade Lunsford

Publications and source records attributed to L Dade Lunsford.

At least 55 records · Page 3Linked to original sources

Stereotactic radiosurgery for brain metastases from gastrointestinal tract cancer.

BACKGROUND: Outcomes in patients with brain metastases from gastrointestinal tract cancers are not well defined. In this study we used precise, single-session, focal tumor irradiation (radiosurgery) in patients with brain metastases and evaluated the results. METHODS: Thirty-nine patients had brain metastases from gastrointestinal tract cancer and were treated with radiosurgery. Thirty-two also had whole brain radiotherapy. Primary lesions included colorectal cancer (n = 25), esophageal cancer (n = 11), cholangiocarcinoma (n = 1), duodenal cancer (n = 1), and jejunal cancer (n = 1). Seventy-two tumors were treated. RESULTS: The overall median survival was 9 months after diagnosis of metastatic brain disease and 5 months after radiosurgery. The 1-year survival rate after radiosurgery was 19%. The last imaging study of 49 tumors showed complete remission (CR) in 3 tumors (6.1%), partial remission (PR) in 27 tumors (55.1%), no change (NC) in 11 tumors (22.4%), and progression in 8 tumors (16.3%). The local tumor control rate (CR, PR, NC) was 84%. Two patients (5.1%) had a new or worsening neurologic deficit after radiosurgery. CONCLUSIONS: Stereotactic radiosurgery provides reasonable local control of brain metastases from gastrointestinal tract cancer with few side effects. However, it should be used judiciously in patients with active extracranial cancers since the expected survival may be limited.

Adult↗

Treatment of rat gliosarcoma brain tumors by HSV-based multigene therapy combined with radiosurgery.

Our laboratory has employed replication-defective herpes simplex virus type 1 gene transfer vectors for treatment of animal models of human malignant glioblastoma. The base vectors were defective for the immediate early (IE) genes ICP4, ICP27, and ICP22 but expressed the IE gene ICP0, which can arrest tumor cell division, and an IE thymidine kinase (alpha-tk) gene construct that mediates suicide gene therapy (SGT) in the presence of ganciclovir (GCV). Previously, we reported that SGT using ICP0/alpha-tk vectors in nude mouse models of glioblastoma was improved by coexpression of the gap-junction-forming protein connexin43 (Cx43) or human tumor necrosis factor alpha (TNF alpha). We also showed that further gains in therapeutic outcome could be achieved by combining TNF alpha-enhanced SGT with gamma-knife radiosurgery (GKR). To expand these observations, we have first repeated these studies in immunocompetent rats with brain tumors derived from implanted 9L gliosarcoma cells and second compared the most efficient vector from this study with a new recombinant vector, NUREL-C2, which expressed both TNF alpha and Cx43 along with ICP0 and alpha-tk. Results from the first part indicated that our ICP0/alpha-tk/TNF alpha vector in combination with GKR provides an effective therapy although this treatment was not statistically better than GKR combined with the ICP0/alpha-tk/Cx43 vector. Our observations in the second part suggested that NUREL-C2 may be more effective than the ICP0/alpha-tk/TNF alpha vector in combination treatments with GCV (P = 0.08) or GCV plus GKR (P = 0.10). GKR significantly enhanced the efficacy of NUREL-C2/GCV treatment (P = 0.02) as well as other virus/GCV treatments (P < or = 0.05). Conversely, the efficacy of GKR was significantly improved by both the ICP0/alpha-tk/TNF alpha vector and NUREL-C2 in combination with GCV (P = 0.02 and P < 0.01, respectively). Together these results indicate that NUREL-C2 may be an attractive candidate for Phase I gene-therapy safety studies in patients with recurrent malignant glioblastoma.

Animals↗

Long-term results after radiosurgery for benign intracranial tumors.

BACKGROUND: Stereotactic radiosurgery is the principal therapeutic alternative to resecting benign intracranial tumors. The goals of radiosurgery are the long-term prevention of tumor growth, the maintenance of patient function, and the prevention of new neurological deficits or adverse radiation effects. Evaluation of long-term outcomes more than 10 years after radiosurgery is needed. METHODS: We evaluated 285 consecutive patients who underwent radiosurgery for benign intracranial tumors between 1987 and 1992. Serial imaging studies were obtained, and clinical evaluations were performed. Our series included 157 patients with vestibular schwannomas, 85 patients with meningiomas, 28 patients with pituitary adenomas, 10 patients with other cranial nerve schwannomas, and 5 patients with craniopharyngiomas. Prior surgical resection had been performed in 44% of these patients, and prior radiotherapy had been administered in 5%. The median follow-up period was 10 years. RESULTS: Overall, 95% of the 285 patients in this series had imaging-defined local tumor control (63% had tumor regression, and 32% had no further tumor growth). The actuarial tumor control rate at 15 years was 93.7%. In 5% of the patients, delayed tumor growth was identified. Resection was performed after radiosurgery in 13 patients (5%). No patient developed a radiation-induced tumor. Eighty-one percent of the patients were still alive at the time of this analysis. Normal facial nerve function was maintained in 95% of patients who had normal function before undergoing treatment for acoustic neuromas. CONCLUSION: Stereotactic radiosurgery provided high rates of tumor growth control, often with tumor regression, and low morbidity rates in patients with benign intracranial tumors when evaluated over the long term. This study supports radiosurgery as a reliable alternative to surgical resection for selected patients with benign intracranial tumors.

Adolescent↗

Stereotactic radiosurgery for CNS nongerminomatous germ cell tumors. Report of four cases.

In this study, we evaluated the results in four patients with nongerminomatous germ cell tumors (NGGCT) of the pineal region. All underwent radiosurgery in conjunction with surgical resection, fractionated radiotherapy or chemotherapy. Four male patients with pineal region NGGCT were treated with radiosurgery. The mean age was 16.5 years. Three patients had histological confirmation by stereotactic biopsy or craniotomy prior to radiosurgery. One patient was diagnosed by serum and CSF tumor markers. The mean tumor volume was 10.5 cm(3). Radiosurgery was performed with mean maximum and marginal doses of 28 and 14 Gy, respectively. At last follow-up, three patients were alive and one was dead. The mean follow-up after diagnosis and after radiosurgery was 34 and 25 months, respectively. At last follow-up, two tumors had regressed, one was unchanged and one had progressed. No patient had complications after radiosurgery. Radiosurgery can play an important adjuvant role for NGGCT patients who also undergo multimodal management. In the case of prepubertal patients, radiosurgery may play an important role by reducing the radiation dose to the surrounding normal brain.

Adolescent↗

Radiobiological analysis of tissue responses following radiosurgery.

Stereotactic radiosurgery provided clinicians the ability to administer high single-doses of radiation to intracranial targets with relative safety. Analysis of clinical outcome from radiosurgery calls into question some of the radiobiological principles that have guided conventional fractionated radiotherapy in the past. The response of the tumor or target tissue being irradiated, as well as the response of the surrounding normal tissue, seems predominantly determined by the tumor or target vasculature. Injury to the tumor or target vasculature appears to contribute to the probability of developing normal tissue complications. Estimations of alpha/beta values from radiosurgical dose-response data consistently yield values that conflict with values from fractionated radiotherapy and with linear-quadratic theory. This indicates that projections from high-dose single-fractions to fractionated dose-equivalents made using the linear-quadratic formula are unreliable. Radiobiological analysis of clinical data from radiosurgery provides models for guiding treatment to achieve desired effects and provide reliable estimates of complications.

Dose Fractionation, Radiation↗

Brain metastases treated with radiosurgery alone: an alternative to whole brain radiotherapy?

OBJECTIVE: Whole brain radiotherapy (WBRT) provides benefit for patients with brain metastases but may result in neurological toxicity for patients with extended survival times. Stereotactic radiosurgery in combination with WBRT has become an important approach, but the value of WBRT has been questioned. As an alternative to WBRT, we managed patients with stereotactic radiosurgery alone, evaluated patients' outcomes, and assessed prognostic factors for survival and tumor control. METHODS: One hundred seventy-two patients with brain metastases were managed with radiosurgery alone. One hundred twenty-one patients were evaluable with follow-up imaging after radiosurgery. The median patient age was 60.5 years (age range, 16-86 yr). The mean marginal tumor dose and volume were 18.5 Gy (range, 11-22 Gy) and 4.4 ml (range, 0.1-24.9 ml). Eighty percent of patients had solitary tumors. RESULTS: The overall median survival time was 8 months. The median survival time in patients with no evidence of primary tumor disease or stable disease was 13 and 11 months. The local tumor control rate was 87%. At 2 years, the rate of local control, remote brain control, and total intracranial control were 75, 41, and 27%, respectively. In multivariate analysis, advanced primary tumor status (P = 0.0003), older age (P = 0.008), lower Karnofsky Performance Scale score (P = 0.01), and malignant melanoma (P = 0.005) were significant for poorer survival. The median survival time was 28 months for patients younger than 60 years of age, with Karnofsky Performance Scale score of at least 90, and whose primary tumor status showed either no evidence of disease or stable disease. Tumor volume (P = 0.02) alone was significant for local tumor control, whereas no factor affected remote or intracranial tumor control. Eleven patients developed complications, six of which were persistent. Nineteen (16.5%) of 116 patients in whom the cause of death was obtained died as a result of causes related to brain metastasis. CONCLUSION: Brain metastases were controlled well with radiosurgery alone as initial therapy. We advocate that WBRT should not be part of the initial treatment protocol for selected patients with one or two tumors with good control of their primary cancer, better Karnofsky Performance Scale score, and younger age, all of which are predictors of longer survival.

Adolescent↗

Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control.

OBJECT: Renal cell carcinoma is a leading cause of death from cancer and its incidence is increasing. In many patients with renal cell cancer, metastasis to the brain develops at some time during the course of the disease. Corticosteroid therapy, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, the median survival in patients with renal cell carcinoma metastasis is approximately 3 to 6 months. In this study the authors examined the efficacy of gamma knife surgery in treating renal cell carcinoma metastases to the brain and evaluated factors affecting long-term survival. METHODS: The authors conducted a retrospective review of 69 patients undergoing stereotactic radiosurgery for a total of 146 renal cell cancer metastases. Clinical and radiographic data encompassing a 14-year treatment interval were collected. Multivariate analyses were used to determine significant prognostic factors influencing survival. The overall median length of survival was 15 months (range 1-65 months) from the diagnosis of brain metastasis. After radiosurgery, the median survival was 13 months in patients without and 5 months in those with active extracranial disease. In a multivariate analysis, factors significantly affecting the rate of survival included the following: 1) younger patient age (p = 0.0076); 2) preoperative Karnofsky Performance Scale score (p = 0.0012); 3) time from initial cancer diagnosis to brain metastasis diagnosis (p = 0.0017); 4) treatment dose to the tumor margin (p = 0.0252); 5) maximal treatment dose (p = 0.0127); and 6) treatment isodose (p = 0.0354). Prior tumor resection, chemotherapy, immunotherapy, or whole-brain radiation therapy did not correlate with extended survival. Postradiosurgical imaging of the brain demonstrated that 63% of the metastases had decreased, 33% remained stable, and 4% eventually increased in size. Two patients (2.9%) later underwent a craniotomy and resection for a tumor refractory to radiosurgery or a new symptomatic metastasis. Eighty-three percent of patients died of progression of extracranial disease. CONCLUSIONS: Stereotactic radiosurgery for treatment of renal cell carcinoma metastases to the brain provides effective local tumor control in approximately 96% of patients and a median length of survival of 15 months. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can offer patients an extended survival.

Adult↗

Acoustic tumors: operation versus radiation--making sense of opposing viewpoints. Part II. Acoustic neuromas: sorting out management options.

Patients with acoustic neuromas have several options available to them. Large tumors with significant brain stem compression usually require surgical resection. For patients with small or medium-sized tumors, radiosurgery has become a common treatment, with excellent long-term results being reported. Patients must be comfortable with the concept of tumor control rather than tumor removal. Most seem to be satisfied with this concept if it allows them to avoid brain surgery. Surgeons should strive to educate their patients with information from the peer-reviewed literature. Confusion exists among patients, because the information from Internet sources, newsletters, support groups, and physicians has not always been validated and supported by outcomes data. Although we are asked to provide our opinions, our comments should not be based on myth, conjecture, training bias, or socioeconomic concerns.

Decision Making↗

Analysis of repeat stereotactic radiosurgery for progressive primary and metastatic CNS tumors.

PURPOSE: To identify and evaluate the pretreatment and patient factors that would predict for complications after repeat radiosurgery. METHODS AND MATERIALS: The data from 26 patients who underwent re-irradiation with Gamma Knife surgery after a previous procedure in the same or subjacent location were available for evaluation. The range of follow-up was 1-45 months (mean 10). The mean minimal and maximal initial dose and volume for all 26 patients was 16.2 Gy (range 12-22), 31.0 Gy (range 22.2-40.0), and 12.4 cm(3) (range 1.20-70.84), respectively. The mean marginal and maximal repeated radiosurgery dose and volume for all 26 patients was 14.9 Gy (range 12-22.5), 29.7 Gy (range 18.0-45.0) and 12.8 cm(3) (range 1.10-39.20), respectively. RESULTS: Tumor control was significantly better statistically (p = 0.0129) for benign tumors (6 of 6, 100% actuarial rate at 4 years) compared with malignant tumors (7 of 20, 35% actuarial rate at 3 years, 3 of 4 metastatic tumors and 2 of 10 primary malignant gliomas). The retreatment volume for radiosurgery correlated significantly with the probability of neurologic decline (any cause) (p = 0.0181). CONCLUSION: Repeat radiosurgery can be performed for recurrent tumors with minimal central nervous system toxicity, especially for benign tumors, with reasonable tumor control.

Adolescent↗

An analysis of the dose-response for arteriovenous malformation radiosurgery and other factors affecting obliteration.

PURPOSE: The aim of this study was to better understand arteriovenous malformation (AVM) obliteration rates after radiosurgery. METHODS AND MATERIALS: We studied obliteration after Gamma knife radiosurgery in 351 AVM patients with 3-11 years of follow-up imaging. The median marginal dose was 20 Gy (range: 12-30) and median treatment volume was 5.7 cm(3) (range: 0.26-24). Stereotactic targeting was with angiography alone in 250 AVMs, and additional magnetic resonance (MR) imaging in 101 AVMs. RESULTS: We documented obliteration by angiography in 193/264 (73%) AVM, and by MR alone in 75/87 (86%) AVM for a 75% corrected obliteration rate. We identified persistent out-of-field nidus in 18% of embolized vs. 5% of non-embolized patients, (P = 0.006). Multivariate analysis correlated in-field obliteration with marginal dose (P < 0.0001) and sex (P < or = 0.026, but not for overall obliteration P = 0.19). A mathematical dose-response model for overall obliteration was constructed to generate a dose-response curve for AVM obliteration with a maximum overall obliteration rate of 88% and minimal improvement above 25 Gy. We could not define the value of alpha/beta for AVM obliteration to a level of statistical significance. CONCLUSION: The rate of AVM obliteration from radiosurgery depends on the marginal dose administered with a dose-response curve that reaches a maximum of approximately 88%. The dose-response plateau reflects problems with target definition which is made more difficult by prior embolization.

Adolescent↗

Repeat radiosurgery for refractory trigeminal neuralgia.

OBJECTIVE: Stereotactic radiosurgery has become an important and minimally invasive alternative for patients with refractory trigeminal neuralgia. When a second procedure is necessary, the outcomes are unknown. The degree of pain relief and morbidity after repeat radiosurgery were studied. METHODS: Thirty-one patients underwent a second gamma knife radiosurgery procedure because of unsatisfactory or unsustained relief of pain after the first procedure. Twenty-seven patients were assessable at median follow-up periods of 42.7 and 20.4 months after the first and second procedures, respectively. Most patients had undergone multiple previous operations of other types (microvascular decompression, radiofrequency rhizotomy, glycerol rhizotomy, balloon compression). The median target doses of the first and second radiosurgeries were 75 and 64 Gy, respectively. All patients were evaluated by a physician who did not participate in patient treatment. RESULTS: After the first radiosurgical procedure, 13 patients had an excellent response initially (complete relief without any medication), 3 had a good response (complete relief with some medication), 7 had a fair response (>50% relief), and 4 had a poor response (<50% pain relief or treatment failure). Repeat radiosurgery was performed in patients with recurrent or residual pain. After the second radiosurgical procedure, 5 patients had an excellent response, 8 had a good response, 10 had a fair response, and 4 had a poor response. Thirteen patients (48%) achieved complete pain relief (with or without medication). Two patients (7.4%) experienced new sensory symptoms after the first radiosurgical procedure, and three (12.7%, actuarial) experienced new sensory symptoms after the second procedure. CONCLUSION: Repeat radiosurgery provided a similar rate of pain relief as the first procedure, despite a modest dose reduction. The risk of new sensory symptoms was increased, but no other morbidity was identified. For patients who experience recurrent pain and choose to undergo a second procedure, our current procedure is to deliver a maximum dose of 50 to 60 Gy to a trigeminal target anterior to the root entry zone near the entrance of the nerve beneath the petrous dura.

Adult↗

Long-term results after stereotactic radiosurgery for patients with cavernous malformations.

OBJECTIVE: Stereotactic radiosurgery has been used for patients with high-risk cavernous malformations of the brain. We performed radiosurgery for patients with symptomatic, imaging-confirmed hemorrhages for which resection was believed to be associated with high risk. This study examines the long-term hemorrhage rate after radiosurgery. METHODS: We reviewed data obtained before and after gamma knife radiosurgery on 82 patients treated between 1987 and 2000. Most patients had multiple hemorrhages from brainstem or diencephalic cavernous malformations. Follow-up data were examined to identify hemorrhages, and an overall hemorrhage rate was calculated. RESULTS: Observation before treatment averaged 4.33 years (range, 0.17-18 yr) for a total of 354 patient-years. During this period, 202 hemorrhages were observed, for an annual hemorrhage rate of 33.9%, excluding the first hemorrhage. Temporal clustering of hemorrhages was not significant. After radiosurgery, patient follow-up averaged 5 years (range, 0.42-12.08 yr), for a total of 401 patient-years. During this period, 19 hemorrhages were identified, 17 in the first 2 years posttreatment and 2 after 2 years. The annual hemorrhage rate was 12.3% per year for the first 2 years after radiosurgery, followed by 0.76% per year from Years 2 to 12. Eleven patients had new neurological symptoms without hemorrhage after radiosurgery (13.4%). The symptoms were minor in six of these patients and temporary in five. CONCLUSION: Radiosurgery confers a reduction in the risk of hemorrhage for high-risk cavernous malformations. Risk reduction, although in evidence during initial follow-up, is most pronounced after 2 years. Given the difficulty of identifying high-risk patients, treatment after one major hemorrhage should be considered in selected younger patients. Such a strategy warrants further investigation.

Cerebral Hemorrhage↗

The role of radiosurgery for the treatment of pineal parenchymal tumors.

OBJECTIVE: Radiosurgery is an appealing alternative management strategy for selected patients with biopsy-proved pineal parenchymal tumors. The purpose of this report was to clarify its role in conjunction with other surgical, radiation, and medical approaches. METHODS: We retrospectively evaluated 16 patients who had undergone radiosurgery as the primary or adjuvant treatment for pineal parenchymal tumors. Ten patients (62.5%) had pineocytomas, two (12.5%) had mixed pineocytoma and pineoblastoma, and four (25%) had pineoblastomas. The mean marginal dose was 15 Gy, and the mean tumor volume was 5.0 cm(3). The mean follow-up periods from the time of diagnosis or the time of radiosurgery were 61 and 52 months, respectively. RESULTS: The overall actuarial 2- and 5-year survival rates after diagnosis were 75.0 and 66.7%, respectively. In 14 patients who were evaluated with imaging, 4 (29%) demonstrated complete remission, 8 (57%) had partial remission, 2 (14%) had no change, and no patient had local progression. The local tumor control rate (complete remission, partial remission, or no change) was 100%. Five patients died during follow-up. One patient with a pineocytoma and three patients with pineoblastomas died secondary to leptomeningeal or extracranial spread tumor. No cause of death was established for one patient. Two patients developed adverse radiation effects after radiosurgery. CONCLUSION: Our initial experience suggests that stereotactic radiosurgery is a valuable primary management modality for patients with pineocytomas. As adjuvant therapy, radiosurgery may be used to boost local tumor dose during multimodality management of malignant pineal parenchymal tumors.

Adolescent↗

Radiosurgery for treatment of recurrent intracranial hemangiopericytomas.

OBJECTIVE: Hemangiopericytomas are highly aggressive meningeal tumors with tendencies for recurrence and metastasis. The purpose of this retrospective, single-institution review was to evaluate the efficacy and role of stereotactic radiosurgery in the management of recurrent hemangiopericytomas. METHODS: We reviewed data for patients who underwent stereotactic radiosurgery at the University of Pittsburgh between 1987 and 2001. Fourteen patients underwent radiosurgery for 15 discrete tumors. Prior treatments included transsphenoidal resection (n = 1), craniotomy and resection (n = 27), embolization (n = 1), and conventional radiotherapy (n = 7). Clinical and radiological responses were evaluated. Follow-up periods varied from 5 to 76 months (mean, 31.3 mo; median, 21 mo). The mean radiation dose to the tumor margin was 15 Gy. RESULTS: Seventy-nine percent of patients (11 of 14 patients) with recurrent hemangiopericytomas demonstrated local tumor control after radiosurgery. Twelve of 15 tumors (i.e., 80%) dramatically decreased in size on follow-up imaging scans. Regional intracranial recurrences were retreated with radiosurgery for two patients (i.e., 15%); neither of those two patients experienced long-term tumor control. Local recurrences occurred 12 to 75 months (median, 21 mo) after radiosurgery. Local tumor control and survival rates at 5 years after radiosurgery were 76 and 100%, respectively (Kaplan-Meier method). We could not correlate prior irradiation or tumor size with tumor control. Twenty-nine percent of the patients (4 of 14 patients) developed remote metastases. Radiosurgery did not seem to offer protection against the development of intra- or extracranial metastases. CONCLUSION: Gamma knife radiosurgery provided local tumor control for 80% of recurrent hemangiopericytomas. When residual tumor is identified after resection or radiotherapy, early radiosurgery should be considered as a feasible treatment modality. Despite local tumor control, patients are still at risk for distant metastasis. Diligent clinical and radiological follow-up monitoring is necessary.

Adolescent↗

Misinterpretation of parahippocampal herniation for a posterior fossa tumor: imaging and intraoperative findings.

Tumors of the hippocampal and parahippocampal gyrus are not uncommon, nor are lesions of the cerebellopontine and ambient cisterns. Lesions in these areas include astrocytomas, meningiomas, gangliogliomas, hamartomas, neurilemomas, epidermoids, and dermoids. Preoperative imaging is an important tool that can help distinguish lesions, making surgical therapy more targeted and appropriate. The authors report a case of a 41-year-old man with right-sided atypical trigeminal neuralgia and a left ambient cistern abnormality that was radiologically interpreted as a mesial temporal lobe or extramedullary ambient cistern mass lesion. Surgical exploration for biopsy revealed an abnormal posterior fossa anatomy and a parahippocampal herniation into the perimesencephalic cistern. Biopsy confirmed the finding of normal brain.

Adult↗