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Purpose: The ultimate goal of stereotactic radiotherapy (SRT) of brain metastases (BM) is to avoid or postpone whole brain radiotherapy (WBRT). A nomogram based on multi-institutional data was developed by Gorovets, et al. to estimate the 6 and 12-months WBRT-free survival (WFS). The aim of the current retrospective study was to validate the nomogram in a cohort of postoperative BM patients treated with adjuvant SRT., Material and Methods: We reviewed the data of 68 patients treated between 2008-2017 with postoperative SRT for BM. The primary endpoint was the WFS. The receiver operating characteristic curve and area under the curve (AUC) were calculated for both 6- and 12-months time points., Results: After a median follow-up of 64 months, the 1-year cumulative incidence of local and distant brain relapse rates were 15% [95% CI=8-26%] and 34% [95% CI=24-48%], respectively. At recurrence, repeated SRT or salvage WBRT were applied in 33% and 57% cases, respectively. The WFS rates at 6 and 12 months were 88% [95% CI=81-97%] and 67% [95% CI=56-81%], respectively. Using the Gorovets nomogram, the 6 months rates were overestimated while they were accurate at 12 months. AUC values were 0.47 and 0.62 for the 6- and 12-months respectively. Overall, Harrell's concordance index was 0.54., Conclusion: This nomogram-predicted well the 12 months WFS but its discriminative power was quite low. This underlines the limits of this kind of predictive tool and leads us to consider the use of big data analysis in the future., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Objective: Management of symptomatic brain metastases often includes surgical resection with postoperative radiotherapy. Postoperative whole-brain radiotherapy (WBRT) improves intracranial control but detrimentally impacts quality of life and neurocognition. We sought to characterize the use in the United States of postoperative stereotactic radiosurgery (SRS), an evolving standard-of-care associated with reduced cognitive effects., Methods: With the MarketScan Commercial Claims and Encounters Database from 2007 to 2015, we identified patients aged 18-65 years treated with resection of a brain metastasis followed by SRS or WBRT within 60 days of surgery. Logistic regression estimated associations between co-variables (treatment year, age, sex, geographic region, place of service, insurance type, disease histology, comorbidity score, and median area household income and educational attainment) and SRS receipt., Results: Of 4007 patients included, 1506 (37.6%) received SRS and 2501 (62.4%) received WBRT. Postoperative SRS increased from 16.5% (2007-2008) to 56.8% (2014-2015). Patients residing in areas with a median household income or an educational attainment below 50th percentile were significantly less likely to receive SRS after controlling for treatment year and other demographic characteristics (P < 0.01). Factors associated with greater odds of receiving SRS included younger age, female sex, melanoma histology, Western region location, hospital-based facility, and high-deductible health plan enrollment (P < 0.05 for each)., Conclusions: Postoperative SRS for brain metastases has increased from 2007 to 2015, with the majority of patients now receiving SRS over WBRT. Patients in areas of lower socioeconomic class were less likely to receive SRS, warranting further investigation of barriers to SRS adoption., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To retrospectively analyze the outcomes of stereotactic radiotherapy (SRT) targeted at surgical bed of brain metastases (BM) and identify patterns of local/distant brain relapses (LR/DBR)., Patients/methods: Seventy patients were treated with SRT between 2008-2017. Marginal dose prescription on the 70% isodose line depended on the maximal diameter of the target volume and range between 15-18Gy for single fraction radiosurgery and 23.1-26Gy in 3-5 fractions for fractionated SRT., Results: At 12 months, the overall survival (OS) was 69% [CI 95% =59%-81%]. At 6 and 12 months, the cumulative incidence functions (CIF) of local relapse were 4% [1%-13%] and 15% [8%-26%], respectively. According to univariate analysis, factors associated with LR were an initial volume larger than 7cc (hazard ratio: 4.6 [1.0-20.8], P=0.046) and a positive resection margin [hazard ratio: 3.6 [1.1-12.0], P=0.037. DBR occurred in 54.3% of patients with a median time of 8 months. None of the variables tested (histology, location or number of lesions) were found correlated with the DBR. Leptomeningeal disease occurred in 12.9% of cases. Salvage whole brain radiotherapy (WBRT) was required in 45.7% of patients and delayed by a median time of 9.6 months. Symptomatic radionecrosis (RN) occurred in 7.1%., Conclusions: Adjuvant SRT was an effective and well-tolerated treatment to control the postoperative risk of recurrence of BM without compromising OS. Positive resection margins and large volumes were predictors factor of local relapse., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: Prophylactic cranial irradiation (PCI) reduces the risk of overt brain metastases in patients with small-cell lung cancer (SCLC) and is currently recommended in guidelines for both limited and extensive disease. Given the concerns about the greater frequency of neurologic side effects in elderly patients, we studied the association among age, PCI usage, and survival for SCLC patients in the Netherlands., Patients and Methods: Data from the Netherlands Cancer Registry for patients diagnosed with SCLC from 2009 to 2013 were queried. Separate analyses were performed for patients with stage I to III, treated with chemoradiotherapy (n = 1684) and patients with stage IV, treated with chemotherapy or chemoradiotherapy (n = 3481). Patients with brain metastasis at diagnosis were excluded., Results: For patients with stage I to III, the overall PCI usage rate was 74%, and the rate decreased with age, from 78% for patients aged 18 to 59 years to 66% for patients aged ≥ 80 years. For patients with stage IV, the overall PCI usage rate was 41% and decreased with age, from 46% for patients aged 18 to 59 years to 23% for patients aged ≥ 80 years. Gender and socioeconomic status did not affect the PCI rates. For patients aged < 70 years and treated with PCI, the median survival was 45, 24, and 12 months for stage I and II, III, and IV, respectively. For patients aged ≥ 70 years treated with PCI, the corresponding survival duration was 33, 17, and 10 months., Conclusion: In the Dutch population, PCI usage rates were fairly high but were significantly lower for elderly patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Patients with single brain metastasis (SBM) have better outcomes after stereotactic radiosurgery (SRS). We analyzed our SRS database to evaluate possible prognostic factors in patients with SBM., Methods: A total of 584 patients with SBM were treated with SRS at our institution (2000-2012). Study end points were overall survival (OS), and distant and local intracranial progression-free survival (DPFS and LPFS, respectively). Multivariable analysis was performed to develop prognostic models., Results: Median OS was 10.8 months. A total of 196 patients (36.7%) had distant progression and 102 patients (19.2%) had local progression. New SBM prognostic indices (SPIs) were devised for OS, DPFS, and LPFS. Graded prognostic assessment, neurologic symptoms (P = 0.01), and tumor volume (P = 0.02) were independently associated with OS. The SPI for OS was defined: unfavorable (OS, 7.3 months), intermediate (OS, 10.6 months), and favorable (OS, 19.8 months). For DPFS, age (P = 0.0029), tumor volume (P = 0.0002), and previous whole-brain radiotherapy (P = 0.027) were prognostic and were used to define SPI for DPFS: favorable (6-month cumulative incidence failure [CIF], 10.9%), intermediate (6-month CIF, 16.7%), and unfavorable (6-month CIF, 26.0%) (P < 0.001). For LPFS, graded prognostic assessment (P = 0.0012) and tumor volume (P = 0.0004) were significant, and defined 2 groups in the LPFS SPI: unfavorable (6-month CIF, 12.3%) and favorable (6-month CIF, 6%) (P < 0.001)., Conclusions: This is the largest series of patients with SBM treated with SRS analyzed for OS, LPFS, and DPFS. SPI was devised for end points. Tumor volume had a significant association with all 3 end points. Neurologic symptoms, age, and previous whole-brain radiotherapy were also found to be prognostic., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Prophylactic cranial irradiation (PCI) was reported to offer survival benefits in patients with limited stage small-cell lung cancer (LS-SCLC). However, earlier studies did not routinely use positron emission tomography (PET) as part of the initial evaluation, thereby reducing the accuracy of tumor staging. We examined the effect of more accurate staging with PET on the role of PCI in patients with LS-SCLC., Patients and Methods: We retrospectively collected data from 280 patients with LS-SCLC who had objective responses after combined chemoradiotherapy between 2001 and 2013. The outcomes of PCI were analyzed after stratifying the patients according to whether or not the initial staging included PET imaging., Results: The risk of brain metastasis as the first site of relapse was lower in patients who received PCI than in those who did not, only in patients without initial PET imaging (13.3% vs. 37.0%; P = .020), but not in patients with initial PET imaging (34.3% vs. 41.1%; P = .243). There was no survival difference between subgroups who received PCI or not (5-year survival rates, 34.8% vs. 34.1%; P = .938). Patients who had initial staging evaluation with PET achieved long-term survival even without PCI (5-year survival rates, 38.3% with PCI, 38.6% without PCI)., Conclusion: The role of PCI needs to be critically reassessed in LS-SCLC patients whose initial staging evaluation included PET because the benefit of PCI was not apparent for them., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Stereotactic radiosurgery (SRS) is widely used to treat brain metastases in place of whole brain radiation therapy (WBRT), with the goal of reducing treatment toxicity balanced against the risk of developing new metastases. We evaluated outcomes of repeated courses of SRS in the management of new brain metastases as an alternative to salvage WBRT., Methods and Materials: We conducted a single-institution retrospective review of 239 patients treated with SRS without WBRT for brain metastases from 2004 to 2014. Eighty-six patients received at least 2 courses of SRS for new brain metastases. Outcome metrics included survival, development of symptomatic new brain metastases, neurologic symptoms at death or last follow-up, and ultimate WBRT., Results: Eighty-six patients (median age, 59 years) underwent a median of 2 courses of SRS (range, 2-6), with a median of 2 lesions treated initially and on retreatment. The median interval between SRS treatments was 5.8 months (range, 1.2-69.1). New brain metastases after initial radiosurgery were detected by routine imaging in 87% of cases. Median overall survival from repeat SRS was 13.0 months (range, 0.3-64.5) and from initial brain metastasis diagnosis 25.0 months (range, 2.0-68.1). On multivariate analysis, Eastern Cooperative Oncology Group performance status 0-1 (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.15-0.90; P=.029), controlled extracranial disease (HR, 0.35; 95% CI, 0.13-0.94; P=.038), and interval between initial and second SRS >6 months (HR, 0.49; 95% CI, 0.25-0.96; P=.037) correlated with improved overall survival from brain metastasis diagnosis. A total of 24.7% of patients had symptomatic intracranial metastatic disease at death or last follow-up, and 26.7% ultimately received WBRT., Conclusion: Repeated SRS is a reasonable option for patients with new brain metastases, as our results suggest favorable survival outcomes with this approach. New lesions infrequently caused neurologic symptoms before routine imaging detection, and a minority of patients had symptomatic intracranial disease at death or last follow-up., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Acromegaly is a chronic rare disease associated with negative pathological effects on multiple systems and organs. We designed a new informatics tool to study data from patients with acromegaly, the Liege Acromegaly Survey (LAS). This relational database permits the inclusion of anonymous historical and prospective data on patients and includes pathophysiology, clinical features, responses to therapy and long term outcomes of acromegaly. We deployed the LAS in a validation study at a single center in order to study the characteristics of patients with acromegaly diagnosed at our center from 1970-2011. A total of 290 patients with acromegaly were included (147 males and 143 females). There was a linear relationship between age at diagnosis and the date of diagnosis, indicating that older patients are being diagnosed with acromegaly more frequently. A majority presented with macroadenomas (77.5%) and the median diameter was 14 mm. Patients with macroadenomas were significantly younger than patients with microadenomas (P=0.01). GH values at diagnosis decreased with the age of the patients (P=0.01) and there was a correlation between GH values and tumor size at diagnosis (P=0.02). No correlation existed between insulin-like growth factor 1 (IGF-1) levels and tumor characteristics. The prevalence of diabetes was 21.4% in this population and 41.0% had hypertension. The presence of hypertension and diabetes were significantly associated with one another (P<0.001). There was a linear relation between initial GH and IGF-1 levels at diagnosis and those obtained during SSA analog treatment and the lowest GH and IGF-1 values following SSA therapy were obtained in older patients (GH: P<0.001; IGF-1: P<0.001). The LAS is a new relational database that is feasible to use in the clinical research setting and permits ready pooling of anonymous patient data from multiple study sites to undertake robust statistical analyses of clinical and therapeutic characteristics., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the oral health status of patients with nasopharyngeal carcinoma (NPC) after completion of radiotherapy., Methods: Thirty-three NPC patients (mean age 53 +/- 10 years) who had completed head and neck radiotherapy (3.6 +/- 3.1 years post-operation) were examined. Dental caries, periodontal status and oral mucosal lesions were recorded. Stimulated whole saliva (SWS) flow rate, pH, buffer capacity and carriage rate of carcinogenic micro-organisms were assessed. Jaw opening was measured., Results: Xerostomia was present in all patients, while 42% had candidiasis and 21% had limited jaw opening. The mean number of teeth present was 22, mean DMFT was 8.0, mean number of untreated root caries lesions was 1.4. Both saliva pH and buffering capacity were low while Streptococcus mutans and Lactobacillus spp. carriage were high. 52% of the patients had no dental care following radiotherapy. Although few patients expressed direct dissatisfaction, perceived level of information and of post-operative dental care was insufficient., Conclusions: Post-irradiated NPC patients constitute a high-risk group for dental root caries and oral candidiasis. The carriage rate of Streptococcus mutans and Lactobacillus spp. in this NPC patient group was the highest among findings of other similar studies. This may be related to the inadequacy of dental care after radiotherapy. Head and neck radiotherapy was not associated with periodontal disease.

In a cohort of 593 long-term survivors of acute lymphocytic leukemia identified through the Children's Cancer Group (CCG), treatment abstracts were obtained and compared to protocol information on radiation therapy and intravenous chemotherapy. This was done in order to evaluate the actual compliance to protocol-specified treatment, and assess if protocol-specified doses can be used in studies of late effects of treatment. The compliance to protocol-specified type of treatment ranged between 95.3% (intrathecal methotrexate) and 98.6% (adriamycin) for chemotherapy, and between 94.1% (cranial radiation) and 97.0% (extended field radiation) for radiation. Concordance with the protocol-specified chemotherapy dose (+/- 25%) was 57.5% for adriamycin, 91.3% for daunomycin, and 48.5% for cyclophosphamide. When concordance was low, most patients received doses that were lower than expected. Concordance with chemotherapy was significantly lower for high-dose regimens than for low-dose regimens. Concordance with protocol-specified radiation dose (+/- 10%) was 87.4% for cranial radiation, 87.8% for spinal radiation, and 85.7% for extended field radiation. Concordance with treatment did not differ by gender, relapse status, or age at diagnosis. In this cohort of leukemia survivors, the validity of type of treatment was greater than the validity of dosage. Great care should be used when drawing conclusions about effects of treatment dosage. Although costly and time consuming, it appears that chart reviews are the most appropriate way to collect information about dose-related effects of therapy.