scholarly journals Injectable diblock copolypeptide hydrogel provides platform to maintain high local concentrations of taxol and local tumor control

2019 ◽  
Author(s):  
Matthew C. Garrett ◽  
Timothy M. O’Shea ◽  
Alexander L. Wollenberg ◽  
Alexander M. Bernstein ◽  
Derek Hung ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Xenograft Model ◽  
Tumor Location ◽  
Local Tumor Control ◽  
Tumor Control ◽  
Local Concentration ◽  
Local Tumor ◽  
Immunodeficient Mice ◽  
Wide Range ◽  
Systemic Side Effects

AbstractIntroductionSurgical resection and systemic chemotherapy with temozolomide remain the mainstay for treatment of glioblastoma. However, many patients are not candidates for surgical resection given inaccessible tumor location or poor health status. Furthermore, despite being first line treatment, temozolomide has only limited efficacy.MethodsThe development of injectable hydrogel-based carrier systems allows for the delivery of a wide range of chemotherapeutics that can achieve high local concentrations, thus potentially avoiding systemic side effects and wide-spread neurotoxicity. To test this modality in a realistic environment, we developed a diblock copolypeptide hydrogel (DCH) capable of carrying and releasing paclitaxel, a compound that we found to be highly potent against primary gliomasphere cells.ResultsThe DCH produced minimal tissue reactivity and was well tolerated in the immune-competent mouse brain. Paclitaxel-loaded hydrogel induced less tissue damage, cellular inflammation and reactive astrocytes than cremaphor-taxol (typical taxol-carrier) or hydrogel alone. In a deep subcortical xenograft model, of glioblastoma in immunodeficient mice, injection of paclitaxel-loaded hydrogel led to a high local concentration of paclitaxel and led to local tumor control and improved survival. However, the tumor cells were highly migratory and were able to eventually escape the area of treatment.ConclusionsThese findings suggest this technology may be ultimately applicable to patients with deep-seated inoperable tumors, but as currently formulated, complete tumor eradication would be highly unlikely. Future studies should focus on targeting the migratory potential of surviving cells.

scholarly journals Injectable diblock copolypeptide hydrogel provides platform to maintain high local concentrations of taxol and local tumor control

2019 ◽  
Author(s):  
Matthew C. Garrett ◽  
Timothy M. O’Shea ◽  
Alexander L. Wollenberg ◽  
Alexander M. Bernstein ◽  
Derek Hung ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Xenograft Model ◽  
Tumor Location ◽  
Local Tumor Control ◽  
Tumor Control ◽  
Local Concentration ◽  
Local Tumor ◽  
Immunodeficient Mice ◽  
Wide Range ◽  
Systemic Side Effects

AbstractIntroductionSurgical resection and systemic chemotherapy with temozolomide remain the mainstay for treatment of glioblastoma. However, many patients are not candidates for surgical resection given inaccessible tumor location or poor health status. Furthermore, despite being first line treatment, temozolomide has only limited efficacy.MethodsThe development of injectable hydrogel-based carrier systems allows for the delivery of a wide range of chemotherapeutics that can achieve high local concentrations, thus potentially avoiding systemic side effects and wide-spread neurotoxicity. To test this modality in a realistic environment, we developed a diblock copolypeptide hydrogel (DCH) capable of carrying and releasing paclitaxel, a compound that we found to be highly potent against primary gliomasphere cells.ResultsThe DCH produced minimal tissue reactivity and was well tolerated in the immune-competent mouse brain. Paclitaxel-loaded hydrogel induced less tissue damage, cellular inflammation and reactive astrocytes than cremaphor-taxol (typical taxol-carrier) or hydrogel alone. In a deep subcortical xenograft model, of glioblastoma in immunodeficient mice, injection of paclitaxel-loaded hydrogel led to a high local concentration of paclitaxel and led to local tumor control and improved survival. However, the tumor cells were highly migratory and were able to eventually escape the area of treatment.ConclusionsThese findings suggest this technology may be ultimately applicable to patients with deep-seated inoperable tumors, but as currently formulated, complete tumor eradication would be highly unlikely. Future studies should focus on targeting the migratory potential of surviving cells.

Linear Accelerator Radiosurgery for Nonvestibular Schwannomas

Neurosurgery ◽  
2011 ◽  
Vol 68 (4) ◽  
pp. 974-984 ◽  
Author(s):  
Matthew M. Kimball ◽  
Kelly D. Foote ◽  
Frank J. Bova ◽  
Yueh-Yun Chi ◽  
William A. Friedman
Keyword(s):  
Surgical Resection ◽  
Cranial Nerve ◽  
Linear Accelerator ◽  
Jugular Foramen ◽  
Symptomatic Improvement ◽  
Local Tumor Control ◽  
Tumor Control ◽  
High Morbidity ◽  
Local Tumor

Abstract BACKGROUND: Nonvestibular schwannomas are uncommon tumors of the brain often treated by surgical resection. Surgery may be associated with high morbidity. OBJECTIVE: We present a series of nonvestibular schwannomas treated with linear accelerator radiosurgery during a 19-year period. METHODS: This is a retrospective analysis of patients who underwent treatment of nonvestibular schwannomas at the University of Florida with linear accelerator radiosurgery between August 1989 and February 2008. Forty-nine patients underwent treatment during the study period, and 6 were lost to follow up. The mean age was 51 years (range, 17-82 years), 39% had previous surgical resection, and 67% presented with preradiosurgery cranial nerve deficits. There were 25 trigeminal, 18 jugular foramen, 2 facial, 2 oculomotor, 1 hypoglossal, and 1 high cervical schwannomas. The median tumor volume was 5.3 mL (range, 0.3-24.5 mL), treated with a median dose of 1250 cGy (range, 1000-1500 cGy). Study endpoints were actuarial local tumor control and neurological outcome. RESULTS: Forty-three patients were available for a median follow-up of 37 months (range, 6-210 months). Actuarial local tumor control was 97% at 1 year, 91% at 4.5 years, and 83% at 5 years. There were 4 new cranial nerve deficits (9%) including facial numbness (2 patients), anesthesia dolorosa (1 patient), and facial weakness (1 patient). Thirty-nine percent had documented clinical and/or symptomatic improvement. There were no other morbidity and no mortality with treatment. CONCLUSION: Radiosurgery for nonvestibular schwannomas offers good actuarial local tumor control and has superior morbidity compared with surgical resection. This is the largest linear accelerator radiosurgical series, and the second largest radiosurgical series reported to date.

Gamma Knife surgery combined with resection for treatment of a single brain metastasis: preliminary results

2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 90-96 ◽  
Author(s):  
M. Yashar S. Kalani ◽  
Aristotelis S. Filippidis ◽  
Maziyar A. Kalani ◽  
Nader Sanai ◽  
David Brachman ◽  
...  
Keyword(s):  
Survival Data ◽  
Initial Treatment ◽  
Median Survival Time ◽  
Local Tumor Control ◽  
Survival Duration ◽  
Tumor Control ◽  
Local Tumor ◽  
Systemic Control ◽  
Cranial Metastasis

Object Resection and whole-brain radiation therapy (WBRT) have classically been the standard treatment for a single metastasis to the brain. The objective of this study was to evaluate the use of Gamma Knife surgery (GKS) as an alternative to WBRT in patients who had undergone resection and to evaluate patient survival and local tumor control. Methods The authors retrospectively reviewed the charts of 150 patients treated with a combination of stereotactic radiosurgery and resection of a cranial metastasis at their institution between April 1997 and September 2009. Patients who had multiple lesions or underwent both WBRT and GKS were excluded, as were patients for whom survival data beyond the initial treatment were not available. Clinical and imaging follow-up was assessed using notes from clinic visits and MR imaging studies when available. Follow-up data beyond the initial treatment and survival data were available for 68 patients. Results The study included 37 women (54.4%) and 31 men (45.6%) (mean age 60 years, range 28–89 years). In 45 patients (66.2%) there was systemic control of the primary tumor when the cranial metastasis was identified. The median duration between resection and radiosurgery was 15.5 days. The median volume of the treated cavity was 10.35 cm3 (range 0.9–45.4 cm3), and the median dose to the cavity margin was 15 Gy (range 14–30 Gy), delivered to the 50% isodose line (range 50%–76% isodose line). The patients' median preradiosurgery Karnofsky Performance Scale (KPS) score was 90 (range 40–100). During the follow-up period we identified 27 patients (39.7%) with recurrent tumor located either local or distant to the site of treatment. The median time from primary treatment of metastasis to recurrence was 10.6 months. The patients' median length of survival (interval between first treatment of cerebral metastasis and last follow-up) was 13.2 months. For the patient who died during follow-up, the median time from diagnosis of cerebral metastasis to death was 11.5 months. The median duration of survival from diagnosis of the primary cancer to last follow-up was 30.2 months. Patients with a pretreatment KPS score ≥ 90 had a median survival time of 23.2 months, and patients with a pretreatment KPS score < 90 had a median survival time of 10 months (p < 0.008). Systemic control of disease at the time of metastasis was not predictive of increased survival duration, although it did tend to improve survival. Conclusions Although the debate about the ideal form of radiation treatment after resection continues, these findings indicate that GKS combined with surgery offers comparable survival duration and local tumor control to WBRT for patients with a diagnosis of a single metastasis.

Petroclival meningiomas: long-term outcomes of multimodal treatments and management strategies based on 30 years of experience at a single institution

2020 ◽  
Vol 132 (6) ◽  
pp. 1675-1682 ◽  
Author(s):  
Jin Wook Kim ◽  
Hee-Won Jung ◽  
Yong Hwy Kim ◽  
Chul-Kee Park ◽  
Hyun-Tai Chung ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Management Strategies ◽  
Local Tumor Control ◽  
Tumor Control ◽  
Years Of Experience ◽  
Local Tumor ◽  
Long Term Outcomes ◽  
Single Institution ◽  
Petroclival Meningiomas

OBJECTIVEA thorough investigation of the long-term outcomes and chronological changes of multimodal treatments for petroclival meningiomas is required to establish optimal management strategies. The authors retrospectively reviewed the long-term clinical outcomes of patients with petroclival meningioma according to various treatments, including various surgical approaches, and they suggest treatment strategies based on 30 years of experience at a single institution.METHODSNinety-two patients with petroclival meningiomas were treated surgically at the authors’ institution from 1986 to 2015. Patient demographics, overall survival, local tumor control rates, and functional outcomes according to multimodal treatments, as well as chronological change in management strategies, were evaluated. The mean clinical and radiological follow-up periods were 121 months (range 1–368 months) and 105 months (range 1–348 months), respectively.RESULTSA posterior transpetrosal approach was most frequently selected and was followed in 44 patients (48%); a simple retrosigmoid approach, undertaken in 30 patients, was the second most common. The initial extent of resection and following adjuvant treatment modality were classified into 3 subgroups: gross-total resection (GTR) only in 13 patients; non-GTR treatment followed by adjuvant radiosurgery or radiation therapy (non-GTR+RS/RT) in 56 patients; and non-GTR without adjuvant treatment (non-GTR only) in 23 patients. The overall progression-free survival rate was 85.8% at 5 years and 81.2% at 10 years. Progression or recurrence rates according to each subgroup were 7.7%, 12.5%, and 30.4%, respectively.CONCLUSIONSThe authors’ preferred multimodal treatment strategy, that of planned incomplete resection and subsequent adjuvant radiosurgery, is a feasible option for the management of patients with large petroclival meningiomas, considering both local tumor control and postoperative quality of life.

Radiosurgery for Treatment of Recurrent Intracranial Hemangiopericytomas

Neurosurgery ◽  
2002 ◽  
Vol 51 (4) ◽  
pp. 905-911 ◽  
Author(s):  
Jason Sheehan ◽  
Douglas Kondziolka ◽  
John Flickinger ◽  
L. Dade Lunsford
Keyword(s):  
Stereotactic Radiosurgery ◽  
Survival Rates ◽  
Gamma Knife Radiosurgery ◽  
Residual Tumor ◽  
Local Tumor Control ◽  
Tumor Control ◽  
Local Tumor ◽  
University Of Pittsburgh ◽  
Kaplan Meier

Abstract 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.

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