Identification of FDGavid- neoplasms may be obscured by high-uptake normal tissues, thus limiting... more Identification of FDGavid- neoplasms may be obscured by high-uptake normal tissues, thus limiting inferences about the natural history of disease. We introduce a FDG-PET radiomics tissue classifier for differentiating FDGavid- normal tissues from tumor. Thirty-three scans from 15 patients with Hodgkin lymphoma and 68 scans from 23 patients with Ewing sarcoma treated on two prospective clinical trials were retrospectively analyzed. Disease volumes were manually segmented on FDG-PET and CT scans. Brain, heart, kidneys and bladder and tumor volumes were automatically segmented on PET images. Standard-uptake-value (SUV) derived shape and first order radiomics features were computed to build a random forest classifier. Manually segmented volumes were compared to automatically segmented tumor volumes. Classifier accuracy for normal tissues was 90%. Classifier performance was varied across normal tissue types (brain, left kidney and bladder, hear and right kidney were 100%, 96%, 97%, 83% a...
To evaluate clinical and dosimetric predictors of trigeminal nerve dysfunction (TND) following st... more To evaluate clinical and dosimetric predictors of trigeminal nerve dysfunction (TND) following stereotactic radiosurgery (SRS) for Trigeminal Neuralgia (TN). We retrospectively reviewed our cohort of 446 patients with TN who underwent SRS between 1999-2008. Median follow-up was 25.1 and 17.4 months (mo) in those with and without TND respectively. Dosimetric and anatomic measurements and clinical features including Burchiel subtype, pain quality, prior procedures, comorbidities, and medications were evaluated for their influence on the TND using univariate and multivariate logistic regression modeling. TND was observed in 44.6% of patients and was similar across facial pain types. Those with TND had prolonged time to pain relapse [(TND, 68.48 mo) vs. (No TND, 29.37 mo)]. Multivariate analysis identified sharp pain at diagnosis (OR 0.594; 95%CI 0.38-0.91), and dorsal root entry zone (DREZ) maximum dose (OR 1.022; 95%CI 1.00-1.04) as predictors of TND. The presence of sharp pain and in...
We investigate clinical, pathologic, and treatment paradigm-related factors affecting local contr... more We investigate clinical, pathologic, and treatment paradigm-related factors affecting local control of brain metastases after stereotactic radiosurgery (SRS) with or without whole brain radiotherapy (WBRT). Patients with brain metastases treated with SRS alone, before or after WBRT were considered to determine predictors of local failure (LF), time to failure and survival. Among 137 patients, 411 brain metastases were analyzed. 23% of patients received SRS alone, 51% received WBRT prior to SRS, and 26% received SRS followed by WBRT. LF occurred in 125 metastases: 63% after SRS alone, 20% after WBRT then SRS, and 22% after SRS then WBRT. Median time to local failure was significantly less after SRS alone compared to WBRT then SRS (12.1 v. 22.7 months, p=0.003). Tumor volume was significantly associated with LF (HR:5.2, p<0.001, 95% CI:3.4-7.8). WBRT+SRS results in reduced LF. Local control was not significantly different after SRS as salvage therapy versus upfront SRS.
Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can ... more Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can avoid WBRT toxicities, but with risk of subsequent distant brain failure (DBF). Sole use of number of metastases to triage patients may be an unrefined method. Data on 1354 patients treated with SRS monotherapy from 2000 to 2013 for new brain metastases was collected across eight academic centers. The cohort was divided into training and validation datasets and a prognostic model was developed for time to DBF. We then evaluated the discrimination and calibration of the model within the validation dataset, and confirmed its performance with an independent contemporary cohort. Number of metastases (≥8, HR 3.53 p = 0.0001), minimum margin dose (HR 1.07 p = 0.0033), and melanoma histology (HR 1.45, p = 0.0187) were associated with DBF. A prognostic index derived from the training dataset exhibited ability to discriminate patients' DBF risk within the validation dataset (c-index = 0.631) ...
A 4-year-old male presented with rapid-onset cranial nerve palsy and ataxia. Brain magnetic reson... more A 4-year-old male presented with rapid-onset cranial nerve palsy and ataxia. Brain magnetic resonance imaging (MRI) revealed a pontine mass lesion with discordant conventional and advanced imaging. A stereotactic core biopsy revealed glioblastoma with immunostaining suggestive of histone H3K27M and TP53 mutation, consistent with diffuse intrinsic pontine glioma. MRI 3 months after radiotherapy revealed extensive new leptomeningeal metastatic disease involving both the supra- and infratentorial brain, as well as the imaged portion of the spine. Tissue procured at the time of needle biopsy has undergone striking in vivo expansion as an orthotopic xenograft.
International Journal of Radiation Oncology*Biology*Physics, 2014
analyses the independent prognostic factors according to the histology of the primary tumor are a... more analyses the independent prognostic factors according to the histology of the primary tumor are as follows: Breast e KPS < 70% (HR Z 1.84); no PTC (HR Z 1.47), no chemotherapy [CT] (HR Z 1.49); no RS (HR Z 2.34). Lung e KPS < 70% (HR Z 1.80); no PTC (HR Z 2.10); no FT (HR Z 2.90 for RS and 1.72 for SG, respectively). Melanoma e no FT (HR Z 4.38 for RS and 2.28 for SG, respectively). GI e no SG (HR Z 4.19). All tumors e KPS < 70% (HR Z 1.70); no PTC (HR Z 1.42); no CT (HR Z 1.42), no FT (HR Z 2.48 for RS and 2.11 for SG, respectively); ECM (HR Z 1.48). *All p value < 0.05. Conclusions: Comparing our data to DS-GPA we observe differences in prognostic factors for breast cancer (PTC, CT and FT), lung cancer (PTC and FT), melanoma (FT) and GI (FT). ECM was just significant when it was analyzed all tumor types together and the number of BM was not an independent factor in this study. The FT was correlated with improved survival in all tumor histology. The inclusion of new prognostic factors could further refine DS-GPA. Author Disclosure: M.G. Silva: None. D.F.G. Neves: None. F.L.C. Faustino: None. D.F. Ferreira: None. A.C.A. Pellizon: None. R.C. Fogaroli: None. D.G. Castro: None. M.J. Chen: None.
The population of adult survivors of childhood cancer continues to grow as survival rates improve... more The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient-specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment-related toxicity and possible targets for intervention in this population. Furthermore, although current long-term follow-up guidelines comprehensively address specific therapy-related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment-re...
Stereotactic radiosurgery for the treatment of brain metastases is commonly delivered without reg... more Stereotactic radiosurgery for the treatment of brain metastases is commonly delivered without regard to primary cancer histology. This study sought to determine if the primary site of origin for brain metastases affected the propensity for local failure. A total of 83 patients with 200 brain metastases were examined retrospectively for predictors of infield failure. Tumor, patient, and treatment characteristics were analyzed including primary tumor histology, radiosurgical dose and age. Cox proportional hazards models, univariate and multivariate analyses were used to identify predictors of local failure. Freedom from local failure for the entire population was 83% and 65% at 6 and 12 months, respectively. Multivariate analysis revealed that breast cancer brain metastases have a significantly lower risk of local failure than melanoma (HR = 0.31, p< 0.001). Additionally, multivariate analysis revealed that increasing dose lowered risk for local failure (HR = 0.87, p<0.001). Mel...
Identification of FDGavid- neoplasms may be obscured by high-uptake normal tissues, thus limiting... more Identification of FDGavid- neoplasms may be obscured by high-uptake normal tissues, thus limiting inferences about the natural history of disease. We introduce a FDG-PET radiomics tissue classifier for differentiating FDGavid- normal tissues from tumor. Thirty-three scans from 15 patients with Hodgkin lymphoma and 68 scans from 23 patients with Ewing sarcoma treated on two prospective clinical trials were retrospectively analyzed. Disease volumes were manually segmented on FDG-PET and CT scans. Brain, heart, kidneys and bladder and tumor volumes were automatically segmented on PET images. Standard-uptake-value (SUV) derived shape and first order radiomics features were computed to build a random forest classifier. Manually segmented volumes were compared to automatically segmented tumor volumes. Classifier accuracy for normal tissues was 90%. Classifier performance was varied across normal tissue types (brain, left kidney and bladder, hear and right kidney were 100%, 96%, 97%, 83% a...
To evaluate clinical and dosimetric predictors of trigeminal nerve dysfunction (TND) following st... more To evaluate clinical and dosimetric predictors of trigeminal nerve dysfunction (TND) following stereotactic radiosurgery (SRS) for Trigeminal Neuralgia (TN). We retrospectively reviewed our cohort of 446 patients with TN who underwent SRS between 1999-2008. Median follow-up was 25.1 and 17.4 months (mo) in those with and without TND respectively. Dosimetric and anatomic measurements and clinical features including Burchiel subtype, pain quality, prior procedures, comorbidities, and medications were evaluated for their influence on the TND using univariate and multivariate logistic regression modeling. TND was observed in 44.6% of patients and was similar across facial pain types. Those with TND had prolonged time to pain relapse [(TND, 68.48 mo) vs. (No TND, 29.37 mo)]. Multivariate analysis identified sharp pain at diagnosis (OR 0.594; 95%CI 0.38-0.91), and dorsal root entry zone (DREZ) maximum dose (OR 1.022; 95%CI 1.00-1.04) as predictors of TND. The presence of sharp pain and in...
We investigate clinical, pathologic, and treatment paradigm-related factors affecting local contr... more We investigate clinical, pathologic, and treatment paradigm-related factors affecting local control of brain metastases after stereotactic radiosurgery (SRS) with or without whole brain radiotherapy (WBRT). Patients with brain metastases treated with SRS alone, before or after WBRT were considered to determine predictors of local failure (LF), time to failure and survival. Among 137 patients, 411 brain metastases were analyzed. 23% of patients received SRS alone, 51% received WBRT prior to SRS, and 26% received SRS followed by WBRT. LF occurred in 125 metastases: 63% after SRS alone, 20% after WBRT then SRS, and 22% after SRS then WBRT. Median time to local failure was significantly less after SRS alone compared to WBRT then SRS (12.1 v. 22.7 months, p=0.003). Tumor volume was significantly associated with LF (HR:5.2, p<0.001, 95% CI:3.4-7.8). WBRT+SRS results in reduced LF. Local control was not significantly different after SRS as salvage therapy versus upfront SRS.
Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can ... more Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can avoid WBRT toxicities, but with risk of subsequent distant brain failure (DBF). Sole use of number of metastases to triage patients may be an unrefined method. Data on 1354 patients treated with SRS monotherapy from 2000 to 2013 for new brain metastases was collected across eight academic centers. The cohort was divided into training and validation datasets and a prognostic model was developed for time to DBF. We then evaluated the discrimination and calibration of the model within the validation dataset, and confirmed its performance with an independent contemporary cohort. Number of metastases (≥8, HR 3.53 p = 0.0001), minimum margin dose (HR 1.07 p = 0.0033), and melanoma histology (HR 1.45, p = 0.0187) were associated with DBF. A prognostic index derived from the training dataset exhibited ability to discriminate patients' DBF risk within the validation dataset (c-index = 0.631) ...
A 4-year-old male presented with rapid-onset cranial nerve palsy and ataxia. Brain magnetic reson... more A 4-year-old male presented with rapid-onset cranial nerve palsy and ataxia. Brain magnetic resonance imaging (MRI) revealed a pontine mass lesion with discordant conventional and advanced imaging. A stereotactic core biopsy revealed glioblastoma with immunostaining suggestive of histone H3K27M and TP53 mutation, consistent with diffuse intrinsic pontine glioma. MRI 3 months after radiotherapy revealed extensive new leptomeningeal metastatic disease involving both the supra- and infratentorial brain, as well as the imaged portion of the spine. Tissue procured at the time of needle biopsy has undergone striking in vivo expansion as an orthotopic xenograft.
International Journal of Radiation Oncology*Biology*Physics, 2014
analyses the independent prognostic factors according to the histology of the primary tumor are a... more analyses the independent prognostic factors according to the histology of the primary tumor are as follows: Breast e KPS < 70% (HR Z 1.84); no PTC (HR Z 1.47), no chemotherapy [CT] (HR Z 1.49); no RS (HR Z 2.34). Lung e KPS < 70% (HR Z 1.80); no PTC (HR Z 2.10); no FT (HR Z 2.90 for RS and 1.72 for SG, respectively). Melanoma e no FT (HR Z 4.38 for RS and 2.28 for SG, respectively). GI e no SG (HR Z 4.19). All tumors e KPS < 70% (HR Z 1.70); no PTC (HR Z 1.42); no CT (HR Z 1.42), no FT (HR Z 2.48 for RS and 2.11 for SG, respectively); ECM (HR Z 1.48). *All p value < 0.05. Conclusions: Comparing our data to DS-GPA we observe differences in prognostic factors for breast cancer (PTC, CT and FT), lung cancer (PTC and FT), melanoma (FT) and GI (FT). ECM was just significant when it was analyzed all tumor types together and the number of BM was not an independent factor in this study. The FT was correlated with improved survival in all tumor histology. The inclusion of new prognostic factors could further refine DS-GPA. Author Disclosure: M.G. Silva: None. D.F.G. Neves: None. F.L.C. Faustino: None. D.F. Ferreira: None. A.C.A. Pellizon: None. R.C. Fogaroli: None. D.G. Castro: None. M.J. Chen: None.
The population of adult survivors of childhood cancer continues to grow as survival rates improve... more The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient-specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment-related toxicity and possible targets for intervention in this population. Furthermore, although current long-term follow-up guidelines comprehensively address specific therapy-related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment-re...
Stereotactic radiosurgery for the treatment of brain metastases is commonly delivered without reg... more Stereotactic radiosurgery for the treatment of brain metastases is commonly delivered without regard to primary cancer histology. This study sought to determine if the primary site of origin for brain metastases affected the propensity for local failure. A total of 83 patients with 200 brain metastases were examined retrospectively for predictors of infield failure. Tumor, patient, and treatment characteristics were analyzed including primary tumor histology, radiosurgical dose and age. Cox proportional hazards models, univariate and multivariate analyses were used to identify predictors of local failure. Freedom from local failure for the entire population was 83% and 65% at 6 and 12 months, respectively. Multivariate analysis revealed that breast cancer brain metastases have a significantly lower risk of local failure than melanoma (HR = 0.31, p< 0.001). Additionally, multivariate analysis revealed that increasing dose lowered risk for local failure (HR = 0.87, p<0.001). Mel...
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Papers by John Lucas