Kristin Redmond

Quantification of Tumor Volume Changes During Radiotherapy for Non–Small-Cell Lung Cancer

PURPOSEnDose escalation for lung cancer is limited by normal tissue toxicity. We evaluated sequential computed tomography (CT) scans to assess the possibility of adaptively reducing treatment volumes by quantifying the tumor volume reduction occurring during a course of radiotherapy (RT).nnnMETHODS AND MATERIALSnA total of 22 patients underwent RT for Stage I-III non-small-cell lung cancer with conventional fractionation; 15 received concurrent chemotherapy. Two repeat CT scans were performed at a nominal dose of 30 Gy and 50 Gy. Respiration-correlated four-dimensional CT scans were used for evaluation of respiratory effects in 17 patients. The gross tumor volume (GTV) was delineated on simulation and all individual phases of the repeat CT scans. Parenchymal tumor was evaluated unless the nodal volume was larger or was the primary. Subsequent image sets were spatially co-registered with the simulation data for evaluation.nnnRESULTSnThe median GTV reduction was 24.7% (range, -0.3% to 61.7%; p < 0.001, two-tailed t test) at the first repeat scan and 44.3% (range, 0.2-81.6%, p < 0.001) at the second repeat scan. The volume reduction was not significantly different between patients receiving chemoradiotherapy vs. RT alone, a GTV >100 cm(3) vs. <100 cm(3), and hilar and/or mediastinal involvement vs. purely parenchymal or pleural lesions. A tendency toward a greater volume reduction with increasing dose was seen, although this did not reach statistical significance.nnnCONCLUSIONnThe results of this study have demonstrated significant alterations in the GTV seen on repeat CT scans during RT. These observations raise the possibility of using an adaptive approach toward RT of non-small-cell lung cancer to minimize the dose to normal structures and more safely increase the dose directed at the target tissues.

Respiratory Motion Changes of Lung Tumors Over the Course of Radiation Therapy Based on Respiration-Correlated Four-Dimensional Computed Tomography Scans

PURPOSEnTo determine whether lung tumor respiratory excursion at simulation is predictive of excursion during radiation and whether phase offsets between tumor and surrogate markers are constant throughout treatment.nnnMETHODS AND MATERIALSnRespiration-correlated CT scans and two rescans (using a Brilliance Big Bore spiral CT simulator; Philips, Inc.) were obtained from 20 patients at simulation. Gross tumor volume (GTV) was contoured on 10 phases of the respiratory cycle, and excursions were calculated. Diaphragm and xyphoid motion were quantified. Phase offsets, DeltaPhi, were calculated for patients with a GTV motion of >3 mm. Interfraction differences in excursions between simulation and rescans and magnitudes of variation in phase offset between fractions were evaluated.nnnRESULTSnMean GTV excursions at simulation in superior-inferior, anterior-posterior, and medial-lateral directions were 0.67, 0.29, and 0.21 cm, respectively. The magnitude of superior-inferior GTV excursion correlated with tumor location (upper vs. lower lobe, p = 0.011). GTV excursions between simulation and rescan 1 (p = 0.115) and between simulation and rescan 2 (p = 0.071) were stable. Fourteen patients were analyzed for variations in phase offsets. GTV-xyphoid phase offset changed significantly between simulation and rescan 1 (p = 0.007) and simulation and rescan 2 (p = 0.008), with mean DeltaPhi values of 13.2% (rescan 1) and 14.3% (rescan 2). Xyphoid-diaphragm offset changed between simulation and rescan 1 (p = 0.004) and between simulation and rescan 2 (p = 0.012), with mean DeltaPhi values of 14.5% (rescan 1) and 7.6% (rescan 2).nnnCONCLUSIONSnInterfraction consistency in tumor excursion suggests tumor excursion at simulation may direct therapy. Significant variations in phase lag between GTV and other anatomic structures throughout treatment have important implications for techniques that rely on surrogate structures to predict tumor motion.

Postradiation imaging changes in the CNS: how can we differentiate between treatment effect and disease progression?

A familiar challenge for neuroradiologists and neuro-oncologists is differentiating between radiation treatment effect and disease progression in the CNS. Both entities are characterized by an increase in contrast enhancement on MRI and present with similar clinical signs and symptoms that may occur either in close temporal proximity to the treatment or later in the disease course. When radiation-related imaging changes or clinical deterioration are mistaken for disease progression, patients may be subject to unnecessary surgery and/or a change from otherwise effective therapy. Similarly, when disease progression is mistaken for treatment effect, a potentially ineffective therapy may be continued in the face of progressive disease. Here we describe the three types of radiation injury to the brain based on the time to development of signs and symptoms--acute, subacute and late--and then review specific imaging changes after intensity-modulated radiation therapy, stereotactic radiosurgery and brachytherapy. We provide an overview of these phenomena in the treatment of a wide range of malignant and benign CNS illnesses. Finally, we review the published data regarding imaging techniques under investigation to address this well-known problem.

Invasive adenoma and pituitary carcinoma: a SEER database analysis

Invasive pituitary adenomas and pituitary carcinomas are clinically indistinguishable until identification of metastases. Optimal management and survival outcomes for both are not clearly defined. The purpose of this study is to use the Surveillance, Epidemiology, and End Results (SEER) database to report patterns of care and compare survival outcomes in a large series of patients with invasive adenomas or pituitary carcinomas. One hundred seventeen patients diagnosed between 1973 and 2008 with pituitary adenomas/adenocarcinomas were included. Eighty-three invasive adenomas and seven pituitary carcinomas were analyzed for survival outcomes. Analyzed prognostic factors included age, sex, race, histology, tumor extent, and treatment. A significant decrease in survival was observed among carcinomas compared to invasive adenomas at 1, 2, and 5xa0years (pu2009=u20090.047, 0.001, and 0.009). Only non-white race, male gender, and age ≥65 were significant negative prognostic factors for invasive adenomas (pu2009=u20090.013, 0.033, and <0.001, respectively). There was no survival advantage to radiation therapy in treating adenomas at 5, 10, 20, or 30xa0years (pu2009=u20090.778, 0.960, 0.236, and 0.971). In conclusion, pituitary carcinoma patients exhibit worse overall survival than invasive adenoma patients. This highlights the need for improved diagnostic methods for the sellar phase to allow for potentially more aggressive treatment approaches.

A radiotherapy technique to limit dose to neural progenitor cell niches without compromising tumor coverage

Radiation therapy (RT) for brain tumors is associated with neurocognitive toxicity which may be a result of damage to neural progenitor cells (NPCs). We present a novel technique to limit the radiation dose to NPC without compromising tumor coverage. A study was performed in mice to examine the rationale and another was conducted in humans to determine its feasibility. C57BL/6 mice received localized radiation using a dedicated animal irradiation system with on-board CT imaging with either: (1) Radiation which spared NPC containing regions; (2) Radiation which did not spare these niches; or (3) Sham irradiation. Mice were sacrificed 24xa0h later and the brains were processed for immunohistochemical Ki-67 staining. For the human component of the study, 33 patients with primary brain tumors were evaluated. Two intensity modulated radiotherapy (IMRT) plans were retrospectively compared: a standard clinical plan and a plan which spares NPC regions while maintaining the same dose coverage of the tumor. The change in radiation dose to the contralateral NPC-containing regions was recorded. In the mouse model, non-NPC-sparing radiation treatment resulted in a significant decrease in the number of Ki67+ cells in dentate gyrus (DG) (Pxa0=xa00.008) and subventricular zone (SVZ) (Pxa0=xa00.005) compared to NPC-sparing radiation treatment. In NPC-sparing clinical plans, NPC regions received significantly lower radiation dose with no clinically relevant changes in tumor coverage. This novel radiation technique should significantly reduce radiation doses to NPC containing regions of the brain which may reduce neurocognitive deficits following RT for brain tumors.

Thoracic Irradiation in the Elderly

This article has reviewed radiation treatment of thoracic malignancies in elderly patients. In general the literature suggests that thoracic irradiation is equally efficacious in elderly patients as in younger patients and is associated with increased but acceptable toxicity. Technical advances are allowing a further reduction in morbidity with preliminary results suggestive of stable outcomes. Prospective data from elderly specific trials are needed to determine the optimal treatment of lung cancer and to compare innovative radiation technology with standard therapies.

A Patient with HIV Treated with Ipilimumab and Stereotactic Radiosurgery for Melanoma Metastases to the Brain

Cancers, such as melanoma, that are associated with immune deficiencies are a major cause of morbidity and mortality in HIV-infected patients. Once patients develop melanoma metastases to the brain, treatment is often limited to palliative surgery and/or radiation. Ipilimumab, a CTLA-4 antagonist, has been shown to improve the median survival of patients with metastatic melanoma. However, available data regarding the safety and efficacy of ipilimumab in HIV-infected patients who develop intracranial melanoma metastases is limited. Here we report our experience administering ipilimumab to a patient with HIV-AIDS who developed multiple intracranial melanoma metastases. Following treatment, our patient showed improvement in systemic tumor control without any apparent interference with antiretroviral treatment.

Progressive Low-Grade Glioma: Assessment of Prognostic Importance of Histologic Reassessment and MRI Findings

BACKGROUNDnIn patients with progressive low-grade glioma (LGG), the presence of new magnetic resonance imaging (MRI) enhancement is commonly used as an indicator of malignant degeneration, but its accuracy in this setting is uncertain.nnnOBJECTIVEnWe characterize the ability of new MRI enhancement to serve as a surrogate for histologic grade in patients with progressive LGG, and to explore the prognostic value of new MRI enhancement, pathologic grade, and extent of resection.nnnMETHODSnPatients at our institution with World Health Organization grade II glioma diagnosed between 1994 and 2010 and who underwent repeat biopsy or resection at progression were retrospectively reviewed (nxa0= 108). The positive predictive value, negative predictive value, sensitivity, and specificity of new MRI enhancement were characterized. A multivariable proportional hazards model was used to test associations with overall survival (OS), and Kaplan-Meier curves were constructed to compare OS between patient subsets.nnnRESULTSnThe positive predictive value, negative predictive value, sensitivity, and specificity of new MRI enhancement were 82%, 77%, 92%, and 57%, respectively. In patients without malignant degeneration, new MRI enhancement was associated with inferior median OS (92.5 months vs. not reached; Pxa0= 0.03). In patients with malignant degeneration, gross or near total resection was associated with improved median OS (58.8 vs. 28.8 months; Pxa0= 0.02).nnnCONCLUSIONnIn patients with progressive LGG, new MRI enhancement and pathologic grade were discordant in greater than 20% of cases. Pathologic confirmation of grade should therefore be attempted, when safe, to dictate management. Beyond functioning as a surrogate for pathologic grade, new MRI enhancement may predict for worse outcomes, a concept that merits prospective investigation.

A prospective study of cerebral, frontal lobe, and temporal lobe volumes and neuropsychological performance in children with primary brain tumors treated with cranial radiation

Cranial radiation therapy (RT) is an important component in the treatment of pediatric brain tumors. However, it can result in long‐term effects on the developing brain. This prospective study assessed the effects of cranial RT on cerebral, frontal lobe, and temporal lobe volumes and their correlation with higher cognitive functioning.

Antiangiogenic Therapies and Extracranial Metastasis in Glioblastoma: A Case Report and Review of the Literature

We present a case report of a patient with glioblastoma multiforme (GBM) complicated by extracranial metastasis (ECM) whose survival of nearly four years surpassed the anticipated life expectancy given numerous negative prognostic factors including EGFRvIII-mutation, unmethylated MGMT promoter status, and ECM. Interestingly, while this patient suffered from locally aggressive disease with multiple intracranial recurrences, the proximal cause of death was progressive extracranial disease and complications related to pulmonary metastases. Herein, we review potential mechanisms of ECM with an emphasis upon glioblastoma molecular and genetic profiles and the potential implications of targeted agents such as bevacizumab.