Citations

The authors compared the relative dosimetric merits of Gamma Knife (GK) and CyberKnife (CK) in 15 patients with 26 brain metastases. All patients were initially treated with the Leksell GK 4C. The same patients were used to generate comparative CK treatment plans. The tissue volume receiving more than 12 Gy (V12), the difference between V12 and tumor volume (V12net), homogeneity index (HI), and gradient indices (GI25, GI50) were calculated. Peripheral dose falloff and three conformity indices were compared. The median tumor volume was 2.50 cm3 (range, 0. 044‐19.9). A median dose of 18 Gy (range, 15‐22) was prescribed. In GK and CK plans, doses were prescribed to the 40‐50% and 77‐92% isodose lines, respectively. Comparing GK to CK, the respective parametric values were: minimum dose ( vs. , ); mean dose ( vs., ); maximum dose ( vs., ); and HI ( vs. , ). The median dosimetric indices (GK vs. CK, with range) were: RTOG_CI, 1.76 (1.12‐4.14) vs. 1.53 (1.16‐2.12), ; CI, 1.76 (1.15‐4.14) vs. 1.55 (1.18‐2.21), ; nCI, 1.76 (1.59‐4.14) vs. 1.57 (1.20‐2.30), ; GI50, 2.91 (2.48‐3.67) vs. 4.90 (3.42‐11.68), ; GI25, 6.58 (4.18‐10.20) vs. 14.85 (8.80‐48.37), . Average volume ratio (AVR) differences favored GK at multiple normalized isodose levels . We concluded that in patients with brain metastases, CK and GK resulted in dosimetrically comparable plans that were nearly equivalent in several metrics, including target coverage and minimum dose within the target. Compared to GK, CK produced more homogenous plans with significantly lower mean and maximum doses, and achieved more conformal plans by RTOG_CI criteria. By GI and AVR analyses, GK plans had sharper peripheral dose falloff in most cases.PACS number: 89.20.‐a

300 Background: The National Radiation Oncology Registry (NROR) is developing an IT infrastructure to support the efficient collection, aggregation, and analysis of data concerning cancer patients treated with radiotherapy across the United States. Methods: Detailed requirements were developed to emphasize the following distinguishing goals for the system: 1) streamline the process of data collection by minimizing manual data entry; 2) support the collection of patient-reported outcomes (PROs) and their linkage with clinician-observed outcomes; 3) facilitate data integration within the NROR and between the NROR and other registries; 4) allow for evolution of the system in response to new learning; and 5) promote sustainability and ongoing improvement through an open standard of interoperability. Results: An innovative technical architecture has been designed to meet the goals described. The system maximizes efficiency through automated extraction and electronic transfer of data from radiation oncology information systems. PROs are collected directly from patients via a web-based portal and linked to data submitted from participating institutions. A data dictionary has been developed based on national standards and controlled vocabularies to facilitate data integration. Contemporary forms-based database technology is used in combination with traditional relational technology to permit both flexible evolution of the system and efficient data analysis. A unique “gateway” architecture and open transmission standard makes it possible for commercial products to interoperate with the registry in the future. Conclusions: The NROR prototype system will be launched later this year to collect data for a pilot registry of prostate cancer patients. Its performance and usability will be important factors in the success of the pilot. If effective, the platform will support the expansion of the NROR to benefit patients, clinicians, researchers, payors, device manufacturers, and policy-makers by capturing reliable, population-based information on radiation treatment delivery and health outcomes.

Abstract Rationale Granulomatous-lymphocytic interstitial lung disease (GLILD) has emerged as a major cause of morbidity in patients with common variable immunodeficiency (CVID). While GLILD is among the most serious noninfectious pulmonary complications of CVID, risk factors for this condition have not been reported. Objectives To identify clinical, physiologic, and serologic risk factors for GLILD in adults with CVID. Methods Of 345 consecutive adult patients with CVID, we identified 34 in the National Jewish Health research database who had a radiographic-pathologic diagnosis of GLILD evaluated between 2002 and 2014. Each case was age and sex matched to 52 CVID control subjects. We used logistic regression to determine independent predictors of GLILD. A mixed effects model was used to estimate the longitudinal change in percent predicted FVC. Measurements and Main Results: The mean time from CVID diagnosis to GLILD detection was 7.8 years. Compared with matched control subjects, cases were more likely to have a history of autoimmune cytopenia, hypersplenism, polyarthritis, lower marginal zone and switched memory B cells, and restrictive lung function. Multivariate analysis revealed that hypersplenism (odds ratio [OR], 24; 95% confidence interval [CI], 4.5–179.1), polyarthritis (OR, 19; 95% CI, 2.3–206.8), and percent predicted FVC (OR, 0.93; 95% CI, 0.87–0.98) were independently associated with the development of GLILD. The rate of change of percent predicted FVC (slope, P = 0.48) did not vary significantly in patients with GLILD over a mean follow-up of 7 years after diagnosis. Conclusions Hypersplenism and polyarthritis are strong risk factors for GLILD in patients with CVID. Percent predicted FVC remained stable over time in patients with GLILD.

Abstract Background Pilocytic astrocytoma is a rare tumor in adults. This report is of a prospective clinical trial with long-term follow-up. Methods Between 1986 and 1994, 20 eligible adults with supratentorial pilocytic astrocytomas were enrolled in a prospective intergroup trial of radiotherapy (RT) after biopsy (3 patients) or observation after gross (11 patients) or subtotal (6 patients) resection. Results At the time of analysis (median follow-up, 20.8 years), 2 patients (10%) have died and 18 patients (90%) are alive. Neurologic and cognitive function were stable or improved over time for the majority of patients. No toxic effects of treatment or malignant transformations have been recorded at last follow-up. For the entire cohort the 20-year time to progression and overall survival rates are 95% and 90% respectively. The cause of death (2.2 and 16.1 years after enrollment) in both patients was unrelated to tumor although both were biopsy-only patients. One subtotally resected tumor progressed 1 month after enrollment requiring P32 injection into an enlarging cyst. Because of further progression this patient required RT 18 months later. This patient is alive without evidence of progression 18 years after RT. Conclusion The long-term follow-up results of this prospective trial confirm that adults with pilocytic astrocytomas have a favorable prognosis with regard to survival and neurologic function. Close observation is recommended for adults with pilocytic astrocytomas, reserving RT for salvage, as the majority remain stable after gross or subtotal resection and no adjuvant therapy.

Purpose Liver injury is a serious adverse event leading to permanent discontinuation of lapatinib in affected patients. This study aimed to validate previously associated major histocompatibility complex (MHC) variants as predictors of risk of liver injury by using a large, randomized, placebo-controlled trial of lapatinib in human epidermal growth factor receptor 2–positive, early-stage breast cancer (Tykerb Evaluation After Chemotherapy [TEACH]: Lapatinib Versus Placebo In Women With Early-Stage Breast Cancer). Patients and Methods The frequency of ALT elevation cases was compared among four MHC variants in 1,194 patients randomly assigned to lapatinib. Cumulative ALT elevation time courses during treatment were also compared between carriers and noncarriers of specified MHC variants. Results In lapatinib-treated patients, there was a significant difference in ALT case incidence between HLA carriers and noncarriers. The highly correlated alleles HLA-DRB1*07:01 and HLA-DQA1*02:01 (study frequency, 22.4%) were associated with ALT elevation (odds ratio, 14) between cases (n = 37) and controls (n = 1,071). These associations strengthened at higher ALT elevation thresholds and in Hy's Law cases. In lapatinib-treated patients, the overall risk for National Cancer Institute-Common Terminology Criteria for Adverse Events grade 3 ALT elevation (> 5× upper limit of normal) was 2.1%; HLA allele carriers had an increased risk of 7.7%; in noncarriers, risk was reduced to 0.5%, comparable to ALT elevation for all patients receiving placebo. The increase in ALT case incidence in the lapatinib arm showed no evidence of plateau during 1 year of lapatinib treatment. Conclusion These results validate HLA-DRB1*07:01 allele carriage as a predictor of increased risk of lapatinib-induced liver injury and implicate an immune pathology. The HLA association could support clinical management of patients experiencing hepatotoxicity during lapatinib treatment.

Background: Because both daptomycin and statins may increase creatine phosphokinase (CPK) levels, the manufacturer of daptomycin suggests considering holding statins during daptomycin therapy. Published evidence suggests potential detrimental effects of withdrawing statin therapy. Objectives: The objectives of this study were to determine the impact of concurrent statin therapy on peak CPK values, incidence of CPK elevation in patients receiving daptomycin therapy, and clinical factors associated with increased risk of developing CPK elevation. Methods: This was a single-center, retrospective cohort study of patients ≥18 years of age who received daptomycin for ≥72 hours and had ≥1 follow-up CPK during a 5-year period. A Kaplan-Meier curve was used to evaluate time to CPK elevation. Cox regression analyses were used to compare the risk of developing elevated CPK between 3 study groups: those receiving daptomycin alone, daptomycin with concurrent statin therapy, and statin therapy held while on daptomycin. Results: 498 patients were included in the study—384 received daptomycin alone, 63 received daptomycin concurrent with statin, and 51 with statin held during daptomycin therapy. Cumulative incidence of CPK elevation was 5.1% and 12% at 7 and 14 days. Those on daptomycin and statin concurrent therapy demonstrated an approximately 2-fold risk of CPK elevation compared with those having their statin therapy held, but the overall group effect was not statistically significant ( P = .17). Conclusions: Our findings suggest that holding statin during daptomycin therapy may not be necessary, but may indicate need for increased frequency of CPK monitoring when these medications are used concurrently.