Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, Jan 22, 2016
A large proportion of patients with non-small cell lung cancer (NSCLC) will develop brain metasta... more A large proportion of patients with non-small cell lung cancer (NSCLC) will develop brain metastases (BM) throughout the course of their disease. Among NSCLC patients with oncogenic drivers, mainly epidermal growth-factor activating mutations and anaplastic lymphoma kinase rearrangements, the presence of BM is a common secondary localisation of disease both at the time of diagnosis and relapse. Due to a limited penetration of a wide range of drugs across the blood-brain barrier, radiotherapy is considered the cornerstone of treatment of BM. However, evidence of dramatic intracranial response rates have been reported in recent years with targeted therapies such as tyrosine kinase inhibitors (TKIs), supported by new insights in pharmacokinetics to increase TKIs cerebrospinal fluid penetration rates. In this context, the combination of brain radiotherapy and targeted therapies seems relevant, and there is a strong radiobiological rationale to harness the radiosentizing effect of the dr...
Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. ... more Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. As systemic therapies improve, patients with lung cancer live longer and thus are at increased risk for brain metastases. Understanding how prognosis varies across this heterogeneous patient population is essential to individualize care and design future clinical trials. To update the current Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with non-small-cell lung cancer (NSCLC) and brain metastases. The DS-GPA is based on data from patients diagnosed between 1985 and 2005, and we set out to update it by incorporating more recently reported gene and molecular alteration data for patients with NSCLC and brain metastases. This new index is called the Lung-molGPA. This is a multi-institutional retrospective database analysis of 2186 patients diagnosed between 2006 and 2014 with NSCLC and newly diagnosed brain metastases. The multivariable analyses took place between De...
CNS metastases are the most common cause of malignant brain tumours in adults. Historically, pati... more CNS metastases are the most common cause of malignant brain tumours in adults. Historically, patients with brain metastases have been excluded from most clinical trials, but their inclusion is now becoming more common. The medical literature is difficult to interpret because of substantial variation in the response and progression criteria used across clinical trials. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group is an international, multidisciplinary effort to develop standard response and progression criteria for use in clinical trials of treatment for brain metastases. Previous efforts have focused on aspects of trial design, such as patient population, variations in existing response and progression criteria, and challenges when incorporating neurological, neuro-cognitive, and quality-of-life endpoints into trials of patients with brain metastases. Here, we present our recommendations for standard response and progression criteria for the assessment of brain metastases in clinical trials. The proposed criteria will hopefully facilitate the development of novel approaches to this difficult problem by providing more uniformity in the assessment of CNS metastases across trials.
International journal of radiation oncology, biology, physics, Jan 25, 2015
A new form of functional imaging has been proposed in the form of 4-dimensional computed tomograp... more A new form of functional imaging has been proposed in the form of 4-dimensional computed tomography (4DCT) ventilation. Because 4DCTs are acquired as part of routine care for lung cancer patients, calculating ventilation maps from 4DCTs provides spatial lung function information without added dosimetric or monetary cost to the patient. Before 4DCT-ventilation is implemented it needs to be clinically validated. Pulmonary function tests (PFTs) provide a clinically established way of evaluating lung function. The purpose of our work was to perform a clinical validation by comparing 4DCT-ventilation metrics with PFT data. Ninety-eight lung cancer patients with pretreatment 4DCT and PFT data were included in the study. Pulmonary function test metrics used to diagnose obstructive lung disease were recorded: forced expiratory volume in 1Â second (FEV1) and FEV1/forced vital capacity. Four-dimensional CT data sets and spatial registration were used to compute 4DCT-ventilation images using a ...
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014
Patients with stage IV non-small-cell lung cancer (NSCLC) who progress through first-line therapy... more Patients with stage IV non-small-cell lung cancer (NSCLC) who progress through first-line therapy have poor progression-free survival (PFS) and overall survival (OS), most commonly failing in original sites of gross disease. Cytoreduction with stereotactic body radiation therapy (SBRT) may help systemic agents delay relapse. Patients in our single arm phase II study had stage IV NSCLC with no more than six sites of extracranial disease who failed early systemic chemotherapy and were able to receive SBRT and concurrent erlotinib until disease progression. After erlotinib commencement, SBRT with equipotent fractionation was delivered to all sites of disease. PFS, OS, and other end points were evaluated. Twenty-four patients (13 men and 11 women) with a median age of 67 years (range, 56-86 years) were enrolled with median follow-up of 11.6 months. All patients had progressed through platinum-based chemotherapy. A total of 52 sites were treated with 16 of 24 patients receiving SBRT to m...
This study evaluates prognostic factors influencing survival outcomes for 50 patients with perman... more This study evaluates prognostic factors influencing survival outcomes for 50 patients with permanent125 iodine-125 implants in the primary treatment of non-GBM high-grade gliomas. Stereotactic treatment planning aimed to encompass the contrast-enhancing rim of the tumor visualized by CT, with an initial dose rate of 0.05 Gy/hour with 125I, delivering 100 Gy at 1 year and 103.68 Gy at infinity. Survival
The aim of this trial was to determine feasibility of incorporating bevacizumab (B) into concurre... more The aim of this trial was to determine feasibility of incorporating bevacizumab (B) into concurrent chemoradiotherapy (CRT) for locally advanced non-small-cell lung cancer (NSCLC). Patients with unresectable stage III NSCLC, performance status of 0 to 1, and adequate organ function were accrued in 2 strata, low- and high-risk (squamous histology, hemoptysis, tumor with cavitation and/or adjacent to a major vessel). Cohort 1 patients received cisplatin 50 mg/m(2) days (d) 1 and 8, etoposide 50 mg/m(2) (d 1-5) for 2 cycles concurrent with radiotherapy (64.8 Gy) followed by docetaxel (D) 75 mg/m(2) and B 15 mg/kg for 3 cycles. If safety was established, then accrual would continue to cohort 2 (B, d 15, 36, 57) and then subsequently to cohort 3 (B, d 1, 22, 43). Twenty-nine patients (17 low- and 12 high-risk) registered to cohort 1. Twenty-six patients (including 4 squamous, 1 adenosquamous) were assessable. Twenty-five completed CRT. Grade 3/4 toxicities during CRT included acceptable ...
To systematically review the evidence for the radiotherapeutic and surgical management of patient... more To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation). Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3). Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3). Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3). It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone).
International Journal of Radiation Oncology*Biology*Physics, 2014
To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gli... more To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology. The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT. The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overall survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of significance were observed for cause-specific survival and OS across analyses. In this large population-based cohort, glioma histology represented a significant predictor for the survival impact of RT. Adjuvant RT was associated with improved survival for AAs, with benefits comparable to those observed for GBMs over the same 10-year interval. No survival advantage was observed with adjuvant RT for AOs.
From January 1992 to November 1996, 17 patients with the diagnosis of intracranial meningioma und... more From January 1992 to November 1996, 17 patients with the diagnosis of intracranial meningioma underwent radiosurgical treatment. Of these, 7 patients were treated using a Linac-based system (group 1), and 10 using the Leksell Gamma Knife unit (group 2). The follow-up ranged between 12 and 48 (median 33) months for group 1 and between 1 and 11 (median 5) months for group 2, consisting of clinical and MRI assessments every 3 months during the first year, and every 6 months thereafter. There were 14 women and 3 men. The mean age was 42 years. Prior to radiosurgery, 15 patients underwent surgical procedures. Histological diagnosis was consistent with benign meningioma, except in 2 patients (malignant meningioma). In 15 patients with benign meningiomas there was no evidence of tumor growth as demonstrated by clinical and radiological evaluation, in 2 patients with a malignant histological type there was tumor progression.
Radiation-induced optic neuropathy is a rare but devastating side effect after radiation treatmen... more Radiation-induced optic neuropathy is a rare but devastating side effect after radiation treatment. The treatment options for radiation-induced optic neuropathy have been limited and largely unsuccessful. A review of the literature was conducted to summarize the rationale and possible benefits of various treatments for radiation-induced optic neuropathy.
Bevacizumab blocks the effects of VEGF and may allow for more aggressive radiotherapy schedules. ... more Bevacizumab blocks the effects of VEGF and may allow for more aggressive radiotherapy schedules. We evaluated the efficacy and toxicity of hypofractionated intensity-modulated radiation therapy with concurrent and adjuvant temozolomide and bevacizumab in patients with newly diagnosed glioblastoma. Patients with newly diagnosed glioblastoma were treated with hypofractionated intensity modulated radiation therapy to the surgical cavity and residual tumor with a 1Â cm margin (PTV1) to 60Â Gy and to the T2 abnormality with a 1Â cm margin (PTV2) to 30Â Gy in 10 daily fractions over 2Â weeks. Concurrent temozolomide (75Â mg/m(2) daily) and bevacizumab (10Â mg/kg) was administered followed by adjuvant temozolomide (200Â mg/m(2)) on a standard 5/28Â day cycle and bevacizumab (10Â mg/kg) every 2Â weeks for 6Â months. Thirty newly diagnosed patients were treated on study. Median PTV1 volume was 131.1Â cm(3) and the median PTV2 volume was 342.6Â cm(3). Six-month progression-free survival (PFS) was 90Â %, wit...
To better define patterns of practice for patients with non-small cell lung cancer (NSCLC) in the... more To better define patterns of practice for patients with non-small cell lung cancer (NSCLC) in the United States. A survey of 36 questions was designed to collect information regarding practice patterns of radiation oncologists for the management of patients with NSCLC. All American Society for Radiation Oncology members were invited to respond. Four hundred twenty-four responses from radiation oncologists in the United States were received. The response rate for the survey was approximately 20%. Substantial discrepancies were seen in the use of stereotactic body radiation therapy (SBRT) for patients with peripherally and centrally located early-stage tumors and in the recommended SBRT dose. There was a near consensus opinion regarding the use of concurrent chemotherapy and the radiation dose for patients with inoperable stage II and III NSCLC with a good performance status; however, in patients with a poor performance status or in patients with stage IV disease treatment recommendat...
Over the past two decades, studies of the Southwest Oncology Group have consistently reported sta... more Over the past two decades, studies of the Southwest Oncology Group have consistently reported stable esophagitis rates despite changing scales with concurrent chest radiotherapy and cisplatin/etoposide regimens. Patient selection has perhaps contributed to increased survival over this period. The Southwest Oncology Group has incorporated surgical questions and advanced the field with a steady use of consistent therapies (ie, cisplatin/etoposide plus radiotherapy of 45 Gy [induction therapy] and cisplatin/etoposide plus at least 61 Gy) in potentially operable or unresectable disease. Further studies examining the addition of either docetaxel or novel agents to such regimens are underway.
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, Jan 22, 2016
A large proportion of patients with non-small cell lung cancer (NSCLC) will develop brain metasta... more A large proportion of patients with non-small cell lung cancer (NSCLC) will develop brain metastases (BM) throughout the course of their disease. Among NSCLC patients with oncogenic drivers, mainly epidermal growth-factor activating mutations and anaplastic lymphoma kinase rearrangements, the presence of BM is a common secondary localisation of disease both at the time of diagnosis and relapse. Due to a limited penetration of a wide range of drugs across the blood-brain barrier, radiotherapy is considered the cornerstone of treatment of BM. However, evidence of dramatic intracranial response rates have been reported in recent years with targeted therapies such as tyrosine kinase inhibitors (TKIs), supported by new insights in pharmacokinetics to increase TKIs cerebrospinal fluid penetration rates. In this context, the combination of brain radiotherapy and targeted therapies seems relevant, and there is a strong radiobiological rationale to harness the radiosentizing effect of the dr...
Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. ... more Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. As systemic therapies improve, patients with lung cancer live longer and thus are at increased risk for brain metastases. Understanding how prognosis varies across this heterogeneous patient population is essential to individualize care and design future clinical trials. To update the current Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with non-small-cell lung cancer (NSCLC) and brain metastases. The DS-GPA is based on data from patients diagnosed between 1985 and 2005, and we set out to update it by incorporating more recently reported gene and molecular alteration data for patients with NSCLC and brain metastases. This new index is called the Lung-molGPA. This is a multi-institutional retrospective database analysis of 2186 patients diagnosed between 2006 and 2014 with NSCLC and newly diagnosed brain metastases. The multivariable analyses took place between De...
CNS metastases are the most common cause of malignant brain tumours in adults. Historically, pati... more CNS metastases are the most common cause of malignant brain tumours in adults. Historically, patients with brain metastases have been excluded from most clinical trials, but their inclusion is now becoming more common. The medical literature is difficult to interpret because of substantial variation in the response and progression criteria used across clinical trials. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group is an international, multidisciplinary effort to develop standard response and progression criteria for use in clinical trials of treatment for brain metastases. Previous efforts have focused on aspects of trial design, such as patient population, variations in existing response and progression criteria, and challenges when incorporating neurological, neuro-cognitive, and quality-of-life endpoints into trials of patients with brain metastases. Here, we present our recommendations for standard response and progression criteria for the assessment of brain metastases in clinical trials. The proposed criteria will hopefully facilitate the development of novel approaches to this difficult problem by providing more uniformity in the assessment of CNS metastases across trials.
International journal of radiation oncology, biology, physics, Jan 25, 2015
A new form of functional imaging has been proposed in the form of 4-dimensional computed tomograp... more A new form of functional imaging has been proposed in the form of 4-dimensional computed tomography (4DCT) ventilation. Because 4DCTs are acquired as part of routine care for lung cancer patients, calculating ventilation maps from 4DCTs provides spatial lung function information without added dosimetric or monetary cost to the patient. Before 4DCT-ventilation is implemented it needs to be clinically validated. Pulmonary function tests (PFTs) provide a clinically established way of evaluating lung function. The purpose of our work was to perform a clinical validation by comparing 4DCT-ventilation metrics with PFT data. Ninety-eight lung cancer patients with pretreatment 4DCT and PFT data were included in the study. Pulmonary function test metrics used to diagnose obstructive lung disease were recorded: forced expiratory volume in 1Â second (FEV1) and FEV1/forced vital capacity. Four-dimensional CT data sets and spatial registration were used to compute 4DCT-ventilation images using a ...
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014
Patients with stage IV non-small-cell lung cancer (NSCLC) who progress through first-line therapy... more Patients with stage IV non-small-cell lung cancer (NSCLC) who progress through first-line therapy have poor progression-free survival (PFS) and overall survival (OS), most commonly failing in original sites of gross disease. Cytoreduction with stereotactic body radiation therapy (SBRT) may help systemic agents delay relapse. Patients in our single arm phase II study had stage IV NSCLC with no more than six sites of extracranial disease who failed early systemic chemotherapy and were able to receive SBRT and concurrent erlotinib until disease progression. After erlotinib commencement, SBRT with equipotent fractionation was delivered to all sites of disease. PFS, OS, and other end points were evaluated. Twenty-four patients (13 men and 11 women) with a median age of 67 years (range, 56-86 years) were enrolled with median follow-up of 11.6 months. All patients had progressed through platinum-based chemotherapy. A total of 52 sites were treated with 16 of 24 patients receiving SBRT to m...
This study evaluates prognostic factors influencing survival outcomes for 50 patients with perman... more This study evaluates prognostic factors influencing survival outcomes for 50 patients with permanent125 iodine-125 implants in the primary treatment of non-GBM high-grade gliomas. Stereotactic treatment planning aimed to encompass the contrast-enhancing rim of the tumor visualized by CT, with an initial dose rate of 0.05 Gy/hour with 125I, delivering 100 Gy at 1 year and 103.68 Gy at infinity. Survival
The aim of this trial was to determine feasibility of incorporating bevacizumab (B) into concurre... more The aim of this trial was to determine feasibility of incorporating bevacizumab (B) into concurrent chemoradiotherapy (CRT) for locally advanced non-small-cell lung cancer (NSCLC). Patients with unresectable stage III NSCLC, performance status of 0 to 1, and adequate organ function were accrued in 2 strata, low- and high-risk (squamous histology, hemoptysis, tumor with cavitation and/or adjacent to a major vessel). Cohort 1 patients received cisplatin 50 mg/m(2) days (d) 1 and 8, etoposide 50 mg/m(2) (d 1-5) for 2 cycles concurrent with radiotherapy (64.8 Gy) followed by docetaxel (D) 75 mg/m(2) and B 15 mg/kg for 3 cycles. If safety was established, then accrual would continue to cohort 2 (B, d 15, 36, 57) and then subsequently to cohort 3 (B, d 1, 22, 43). Twenty-nine patients (17 low- and 12 high-risk) registered to cohort 1. Twenty-six patients (including 4 squamous, 1 adenosquamous) were assessable. Twenty-five completed CRT. Grade 3/4 toxicities during CRT included acceptable ...
To systematically review the evidence for the radiotherapeutic and surgical management of patient... more To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation). Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3). Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3). Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3). It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone).
International Journal of Radiation Oncology*Biology*Physics, 2014
To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gli... more To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology. The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT. The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overall survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of significance were observed for cause-specific survival and OS across analyses. In this large population-based cohort, glioma histology represented a significant predictor for the survival impact of RT. Adjuvant RT was associated with improved survival for AAs, with benefits comparable to those observed for GBMs over the same 10-year interval. No survival advantage was observed with adjuvant RT for AOs.
From January 1992 to November 1996, 17 patients with the diagnosis of intracranial meningioma und... more From January 1992 to November 1996, 17 patients with the diagnosis of intracranial meningioma underwent radiosurgical treatment. Of these, 7 patients were treated using a Linac-based system (group 1), and 10 using the Leksell Gamma Knife unit (group 2). The follow-up ranged between 12 and 48 (median 33) months for group 1 and between 1 and 11 (median 5) months for group 2, consisting of clinical and MRI assessments every 3 months during the first year, and every 6 months thereafter. There were 14 women and 3 men. The mean age was 42 years. Prior to radiosurgery, 15 patients underwent surgical procedures. Histological diagnosis was consistent with benign meningioma, except in 2 patients (malignant meningioma). In 15 patients with benign meningiomas there was no evidence of tumor growth as demonstrated by clinical and radiological evaluation, in 2 patients with a malignant histological type there was tumor progression.
Radiation-induced optic neuropathy is a rare but devastating side effect after radiation treatmen... more Radiation-induced optic neuropathy is a rare but devastating side effect after radiation treatment. The treatment options for radiation-induced optic neuropathy have been limited and largely unsuccessful. A review of the literature was conducted to summarize the rationale and possible benefits of various treatments for radiation-induced optic neuropathy.
Bevacizumab blocks the effects of VEGF and may allow for more aggressive radiotherapy schedules. ... more Bevacizumab blocks the effects of VEGF and may allow for more aggressive radiotherapy schedules. We evaluated the efficacy and toxicity of hypofractionated intensity-modulated radiation therapy with concurrent and adjuvant temozolomide and bevacizumab in patients with newly diagnosed glioblastoma. Patients with newly diagnosed glioblastoma were treated with hypofractionated intensity modulated radiation therapy to the surgical cavity and residual tumor with a 1Â cm margin (PTV1) to 60Â Gy and to the T2 abnormality with a 1Â cm margin (PTV2) to 30Â Gy in 10 daily fractions over 2Â weeks. Concurrent temozolomide (75Â mg/m(2) daily) and bevacizumab (10Â mg/kg) was administered followed by adjuvant temozolomide (200Â mg/m(2)) on a standard 5/28Â day cycle and bevacizumab (10Â mg/kg) every 2Â weeks for 6Â months. Thirty newly diagnosed patients were treated on study. Median PTV1 volume was 131.1Â cm(3) and the median PTV2 volume was 342.6Â cm(3). Six-month progression-free survival (PFS) was 90Â %, wit...
To better define patterns of practice for patients with non-small cell lung cancer (NSCLC) in the... more To better define patterns of practice for patients with non-small cell lung cancer (NSCLC) in the United States. A survey of 36 questions was designed to collect information regarding practice patterns of radiation oncologists for the management of patients with NSCLC. All American Society for Radiation Oncology members were invited to respond. Four hundred twenty-four responses from radiation oncologists in the United States were received. The response rate for the survey was approximately 20%. Substantial discrepancies were seen in the use of stereotactic body radiation therapy (SBRT) for patients with peripherally and centrally located early-stage tumors and in the recommended SBRT dose. There was a near consensus opinion regarding the use of concurrent chemotherapy and the radiation dose for patients with inoperable stage II and III NSCLC with a good performance status; however, in patients with a poor performance status or in patients with stage IV disease treatment recommendat...
Over the past two decades, studies of the Southwest Oncology Group have consistently reported sta... more Over the past two decades, studies of the Southwest Oncology Group have consistently reported stable esophagitis rates despite changing scales with concurrent chest radiotherapy and cisplatin/etoposide regimens. Patient selection has perhaps contributed to increased survival over this period. The Southwest Oncology Group has incorporated surgical questions and advanced the field with a steady use of consistent therapies (ie, cisplatin/etoposide plus radiotherapy of 45 Gy [induction therapy] and cisplatin/etoposide plus at least 61 Gy) in potentially operable or unresectable disease. Further studies examining the addition of either docetaxel or novel agents to such regimens are underway.
Uploads
Papers by Laurie Gaspar