Thomas B. Daniels

Validation of EORTC Prognostic Factors for Adults With Low-Grade Glioma: A Report Using Intergroup 86-72-51

PURPOSE A prognostic index for survival was constructed and validated from patient data from two European Organisation for Research and Treatment of Cancer (EORTC) radiation trials for low-grade glioma (LGG). We sought to independently validate this prognostic index with a separate prospectively collected data set (Intergroup 86-72-51). METHODS AND MATERIALS Two hundred three patients were treated in a North Central Cancer Treatment Group-led trial that randomized patients with supratentorial LGG to 50.4 or 64.8 Gy. Risk factors from the EORTC prognostic index were analyzed for prognostic value: histology, tumor size, neurologic deficit, age, and tumor crossing the midline. The high-risk group was defined as patients with more than two risk factors. In addition, the Mini Mental Status Examination (MMSE) score, extent of surgical resection, and 1p19q status were also analyzed for prognostic value. RESULTS On univariate analysis, the following were statistically significant (p<0.05) detrimental factors for both progression-free survival (PFS) and overall survival (OS): astrocytoma histology, tumor size, and less than total resection. A Mini Mental Status Examination score of more than 26 was a favorable prognostic factor. Multivariate analysis showed that tumor size and MMSE score were significant predictors of OS whereas tumor size, astrocytoma histology, and MMSE score were significant predictors of PFS. Analyzing by the EORTC risk groups, we found that the low-risk group had significantly better median OS (10.8 years vs. 3.9 years, p<0.0001) and PFS (6.2 years vs. 1.9 years, p<0.0001) than the high-risk group. The 1p19q status was available in 66 patients. Co-deletion of 1p19q was a favorable prognostic factor for OS vs. one or no deletion (median OS, 12.6 years vs. 7.2 years; p=0.03). CONCLUSIONS Although the low-risk group as defined by EORTC criteria had a superior PFS and OS to the high-risk group, this is primarily because of the influence of histology and tumor size. Co-deletion of 1p19q is a prognostic factor. Future studies are needed to develop a more refined prognostic system that combines clinical prognostic features with more robust molecular and genetic data.

Radiation-induced optic neuritis after pituitary adenoma radiosurgery in a patient with multiple sclerosis: case report

Objective and Importance To describe a rare case of optic neuritis onset after Gamma Knife stereotactic radiosurgery. Clinical Presentation Nine years after transsphenoidal subtotal resection of a pituitary adenoma, this 43-year-old woman had elevated serum prolactin levels and headaches. Intervention Gamma Knife stereotactic radiosurgery to residual pituitary tumor. Conclusion To our knowledge, this is the first report of radiation-induced optic neuritis after radiosurgery in a patient with multiple sclerosis.

Prophylactic Cranial Irradiation for Extensive Small-Cell Lung Cancer

Small-cell lung cancer (SCLC) has a high predilection for metastasizing to the brain after chemotherapy. This has been blamed on the blood-brain barrier, which prevents chemotherapy from penetrating into the brain, thus creating a sanctuary site. It has been estimated that up to three quarters of patients with SCLC will eventually develop brain metastases. This led investigators to administer prophylactic cranial irradiation (PCI) to decrease this risk. Several trials were performed in patients with SCLC after initial therapy (chemotherapy with or without thoracic radiotherapy) that compared the outcomes of PCI versus no PCI. Early trials generally found that PCI significantly decreased the risk of brain metastases but did not significantly improve survival. These trials were re-evaluated in two larger meta-analyses that included patients with either limited-stage SCLC or extensive-stage SCLC (ESCLC). Both meta-analyses reported that PCI significantly decreased brain metastases and improved survival in patients who had a complete response following initial therapy. These studies were performed before the advent of modern imaging with computed tomography or magnetic resonance imaging (MRI). There have been two modern trials of PCI versus no PCI in patients with ESCLC and both found that PCI decreases brain metastases. The first did not include brain MRI before registration and found that PCI improved survival, whereas the second study did include MRI before registration and at frequent intervals thereafter. That trial found that PCI did not confer a survival advantage. This review will examine the evidence and provide recommendations regarding the role of PCI for patients with ESCLC.

Factors Associated With Survival Following Radium-223 Treatment for Metastatic Castration-resistant Prostate Cancer

Micro‐Abstract The outcomes of 64 patients with metastatic castration‐resistant prostate cancer after treatment with radium‐223 were analyzed. Four factors were identified to be associated with survival in multivariate analysis. Future studies to evaluate earlier use of this radiopharmaceutical in newly diagnosed metastatic prostate cancer when the disease is sensitive to androgen deprivation therapy would be warranted. Background: Radium‐223 (223Ra) improves survival in patients with metastatic castration‐resistant prostate cancer (mCRPC). This retrospective analysis was performed to better understand its efficacy in routine clinical practice and identify factors associated with survival. Materials and Methods: Sixty‐four patients with mCRPC who received 223Ra between 2013 and 2015 were the basis of this retrospective study. Clinical outcomes and patient characteristics were obtained. Potential prognostic factors for survival were evaluated by univariate analysis using the log‐rank test and multivariate analysis using the Cox proportional hazard method. Results: The median survival was 12.9 months. Twenty‐one patients (33%) developed a skeletal event, and the median time to the first skeletal event was 4.4 months. In univariate analysis, factors significantly associated with survival included: no prior chemotherapy, ≤ 5 bone metastases, baseline prostate‐specific antigen (PSA) ≤ 36 ng/mL, baseline alkaline phosphatase (ALP) < 115 U/L, baseline hemoglobin > 12 g/dL, ALP response after 223Ra treatment, PSA decrease during 223Ra treatment, and absence of > 25% PSA increase during 223Ra treatment. In multivariate analysis, 4 factors remained significant: no prior chemotherapy, ≤ 5 bone metastases, baseline ALP < 115 U/L, and ALP response after 223Ra treatment. Conclusion: When 223Ra is administered in routine clinical practice, clinical outcomes can be more variable than those reported in the randomized study owing to patient heterogeneity. Four factors were identified to be significantly associated with survival after 223Ra treatment. These pretreatment factors may be used as stratification factors in future studies to investigate whether 223Ra would be more effective for patients with newly diagnosed metastatic disease that is sensitive to androgen deprivation therapy.

Proton therapy for sarcomas.

AbstractSarcomas are a heterogeneous group of tumors that can occur in a wide array of anatomic sites and age ranges with varying histologies. Proton beam therapy, as compared with advanced x-ray radiation therapy techniques, can substantially lower dose to nontarget tissues. This dosimetric advantage can potentially allow for improvement of the therapeutic ratio in the treatment of many of the sarcomas by either increasing the local control, via increased dose to the target, or by decreasing the normal tissue complications, via lowered dose to the avoidance structures. This article reviews the key dosimetric studies and clinical outcomes published to date documenting the potential role proton beam therapy may play in the treatment of sarcomas.

Pediatric Metastatic Odontogenic Ghost Cell Carcinoma: A Multimodal Treatment Approach.

Odontogenic ghost cell carcinoma (OGCC) is a rare and aggressive tumor wherein optimal treatment remains uncertain. We report the first pediatric metastatic OGCC case treated with multimodal therapy: surgery, adjuvant chemoradiation, and adjuvant immunotherapy. Adjuvant therapy was utilized due to locally advanced disease with pathologic features indicative of high recurrence risk. This multimodal approach was modeled after management of primary head and neck cancer, where adjuvant chemoradiation and immunotherapy are associated with improved outcomes. Our patient is alive and disease free at 14 months indicating a potentially positive role for multimodal therapy in the management of OGCC.

Conformal Radiation Therapy for Pediatric CNS Tumors

3D conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) are both commonly utilized for pediatric brain tumors. 3DCRT has been available for a longer period. There is protracted follow-up on patients treated with 3DCRT. IMRT is a newer technology that developed in parallel with advances in other radiation delivery such as image guidance. Similar tumor coverage can be either 3DCRT or IMRT. They differ in the ability to achieve conformity around irregularly volumes. IMRT can achieve highly conformal plans although intense modulation can impact dose homogeneity. VMAT is a form of IMRT rotational. The addition of static or rotational beams can expose nontarget tissue to lose dose radiation. The balance of tumor coverage and dose homogeneity against the impact of collateral radiation to nontarget tissues impacting neurocognitive functioning for cranial radiation or anticipated renal and cardiopulmonary function in craniospinal radiation is the main factor in deciding what the optimal photon radiation treatment is for pediatric CNS tumors.

Stereotactic body radiotherapy for early-stage non-small cell lung cancer has low post-treatment mortality

Stereotactic body radiotherapy (SBRT) is increasingly used to treat stage I non-small cell lung cancer (NSCLC). In 2004, less than 0.5% of these cases were managed with SBRT. By 2011, SBRT accounted for 8.7% of cases (1).

Small-spot intensity-modulated proton therapy and volumetric-modulated arc therapies for patients with locally advanced non-small-cell lung cancer: A dosimetric comparative study

Abstract Purpose To compare dosimetric performance of volumetric‐modulated arc therapy (VMAT) and small‐spot intensity‐modulated proton therapy for stage III non‐small‐cell lung cancer (NSCLC). Methods and Materials A total of 24 NSCLC patients were retrospectively reviewed; 12 patients received intensity‐modulated proton therapy (IMPT) and the remaining 12 received VMAT. Both plans were generated by delivering prescription doses to clinical target volumes (CTV) on averaged 4D‐CTs. The dose‐volume‐histograms (DVH) band method was used to quantify plan robustness. Software was developed to evaluate interplay effects with randomized starting phases of each field per fraction. DVH indices were compared using Wilcoxon rank sum test. Results Compared with VMAT, IMPT delivered significantly lower cord Dmax, heart Dmean, and lung V5 Gy[ RBE ] with comparable CTV dose homogeneity, and protection of other OARs. In terms of plan robustness, the IMPT plans were statistically better than VMAT plans in heart Dmean, but were statistically worse in CTV dose coverage, cord Dmax, lung Dmean, and V5 Gy[ RBE ]. Other DVH indices were comparable. The IMPT plans still met the standard clinical requirements with interplay effects considered. Conclusions Small‐spot IMPT improves cord, heart, and lung sparing compared to VMAT and achieves clinically acceptable plan robustness at least for the patients included in this study with motion amplitude less than 11 mm. Our study supports the usage of IMPT to treat some lung cancer patients.

Radiation and the heart: systematic review of dosimetry and cardiac endpoints

ABSTRACT Introduction: Recent trials in radiotherapy have associated heart dose and survival, inadequately explained by the existing literature for radiation-related late cardiac effects. Authors aimed to review the recent literature on cardiac dosimetry and survival/cardiac endpoints. Areas covered: Systematic review of the literature in the past 10 years (2008–2017) was performed to identify manuscripts reporting both cardiac dosimetry and survival/cardiac endpoints. Authors identified 64 manuscripts for inclusion, covering pediatrics, breast cancer, lung cancer, gastrointestinal diseases (primarily esophageal cancer), and adult lymphoma. Expert commentary: In the first years after radiotherapy, high doses (>40 Gy) to small volumes of the heart are associated with decreased survival from an unknown cause. In the long-term, mean heart dose is associated with a small increased absolute risk of cardiac death. For coronary disease, relative risk increases roughly 10% per Gy mean heart dose, augmented by age and cardiac risk factors. For valvular disease and heart failure, doses >15 Gy substantially increase risk, augmented by anthracyclines. Arrhythmias after radiotherapy are poorly described but may account for the association between upper heart dose and survival. Symptomatic pericardial effusion typically occurs with doses >40 Gy. Close follow-up and mitigation of cardiovascular risk factors are necessary after thoracic radiotherapy.