Socio-economic disparities influence likelihood of post-operative radiation to resection cavities of metastatic brain tumors.

PURPOSE: Irradiating the surgical bed of resected brain metastases improves local and distant disease control. Over time, stereotactic radiosurgery (SRS) has replaced whole brain radiotherapy (WBRT) as the treatment standard of care because it minimizes long-term damage to neuro-cognition. Despite this data and growing adoption, socio-economic disparities in clinical access can result in sub-standard care for some patient populations. We aimed to analyze the clinical and socio-economic characteristics of patients who did not receive radiation after surgical resection of brain metastasis. METHODS: Our sample was obtained from Clinformatics® Data Mart Database and included all patients from 2004 to 2021 who did or did not receive radiation treatment within sixty days after resection of tumors metastatic to the brain. Regression analysis was done to identify factors responsible for loss to adjuvant radiation treatment. RESULTS: Of 8362 patients identified who had undergone craniotomy for resection of metastatic brain tumors, 3430 (41%) patients did not receive any radiation treatment. Compared to patients who did receive some form of radiation treatment (SRS or WBRT), patients who did not get any form of radiation were more likely to be older (p = 0.0189) and non-white (p = 0.008). Patients with Elixhauser Comorbidity Index ≥3 were less likely to receive radiation treatment (p < 0.01). Fewer patients with household income ≥ $75,000 did not receive radiation treatment (p < 0.01). CONCLUSION: Age, race, household income, and comorbidity status were associated with differential likelihood to receive post-operative radiation treatment.

Socio-economic outcomes among long-term childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC CLG studies: Results of the 58LAE study.

OBJECTIVE: The objective of this study is to evaluate the socio-economic outcomes of survivors of childhood acute lymphoblastic leukaemia (ALL). METHODS: Childhood ALL adult survivors, enrolled in EORTC trials between 1971 and 1998 in France and Belgium, were invited to fill out a questionnaire with information about their socio-economic situation (living with a partner, having a university degree, having a job, working part time and history of having a paid job). The outcomes were compared with two matched control populations. RESULTS: Among 1418 eligible patients, 507 (35.8%) participated, including 39 (8%) and 61 (12%) patients who received a haematopoietic stem cell transplantation (HSCT) and a cranial radiotherapy (CRT), respectively. The median time to follow-up was 20 years, and median age was 25 years. Survivors showed a socio-economic level at least as good as controls. HCST and CRT were associated with a higher probability of not obtaining a bachelor degree (respectively OR = 3.49, 95% CI: 1.46-8.35 and OR = 2.31, 95% CI: 1.04-5.15), HSCT was associated with unemployment (OR = 2.89, 95% CI: 1.09-7.65) and having a relapse was associated with a higher probability of not having a partner (OR = 1.88, 95% CI: 1.01-3.51) adjusting for confounders. CONCLUSION: Childhood ALL survivors showed a high level of socio-economic participation. HCST and CRT were associated with poorer functioning.

Impact of socio-economic factors on radiation treatment after resection of metastatic brain tumors: trends from a private insurance database.

BACKGROUND: Stereotactic radiosurgery (SRS) to the surgical bed of resected brain metastases is now considered the standard of care due to its advantages over whole brain radiation therapy (WBRT). Despite the upward trend in SRS adoption since the 2000s, disparities have been reported suggesting that socio-economic factors can influence SRS utilization. OBJECTIVE: To analyze recent trends in SRS use and identify factors that influence treatment. METHODS: We conducted a retrospective cohort study with the Optum Commercial Claims and Encounters Database and included all patients from 2004 to 2021 who received SRS or WBRT within 60 days after resection of tumors metastatic to the brain. RESULTS: A total of 3495 patients met the inclusion and exclusion criteria. There were 1998 patients in the SRS group and 1497 patients in the WBRT group. SRS use now supersedes WBRT by a wide margin. Lung, breast and colon were the most common sites of primary tumor. Although we found no significant differences based on race among the treatment groups, patients with annual household income greater than $75,000 and those with some college or higher education are significantly more likely to receive SRS (OR 1.44 and 1.30; 95% CI 1.18-1.76 and 1.08-1.56; P = 0.001 and 0.005, respective). Patients with Elixhauser Comorbidity Index of three or more were significantly more likely to receive SRS treatment. CONCLUSION: The use of post-surgical SRS for brain metastasis has increased significantly over time, however education and income were associated with differential SRS utilization.

Preventive Effect of Hippocampal Sparing on Cognitive Dysfunction of Patients Undergoing Whole-Brain Radiotherapy and Imaging Assessment of Hippocampal Volume Changes.

Objective: Preventive effect of hippocampal sparing on cognitive dysfunction of patients undergoing whole-brain radiotherapy and imaging assessment of hippocampal volume changes. Methods: Forty patients with brain metastases who attended Liaoning Cancer Hospital from January 2018 to December 2019 were identified as research subjects and were randomly divided into a control group and an experimental group, with 20 cases in each group. The control group was treated with whole-brain radiotherapy (WBRT), and the experimental group was treated with hippocampal sparing-WBRT (HS-WBRT). The Montreal Cognitive Assessment (MoCA) score, Eastern Cooperative Oncology Group (ECOG) score, cancer quality-of-life questionnaire (QLQ-C3O) score, hippocampal volume changes, and prognosis of the two groups were compared. Results: The MoCA scores decreased in both groups at 3, 6, and 12 months after radiotherapy, with significantly higher scores in the experimental group than in the control group (P < 0.05). After radiotherapy, both groups had lower ECOG scores, with those in the experimental group being significantly lower than those in the control group (P < 0.05). After radiotherapy, the QLQ-C30 score was elevated in both groups, and that of the experimental group was significantly higher than that of the control group (P < 0.05). The experimental group outperformed the control group in terms of the prognosis (P < 0.05). The hippocampal volume of the control group was significantly smaller than that of the experimental group (P < 0.05). Conclusion: The application of hippocampal sparing in patients receiving whole-brain radiotherapy is effective in preventing cognitive dysfunction, improving the quality of life and prognosis of patients, and avoiding shrinkage of hippocampal volume.

Cost-effectiveness of prophylactic cranial irradiation in stage III non-small cell lung cancer.

INTRODUCTION: In stage III non-small cell lung cancer (NSCLC), prophylactic cranial irradiation (PCI) reduces the brain metastases incidence and prolongs the progression-free survival without improving overall survival. PCI increases the risk of toxicity and is currently not adopted in routine care. Our objective was to assess the cost-effectiveness of PCI compared with no PCI in stage III NSCLC from a Dutch societal perspective. METHODS: A cohort partitioned survival model was developed based on individual patient data from three randomized phase III trials (N = 670). Quality-adjusted life years (QALYs) and costs were estimated over a lifetime time horizon. A willingness-to-pay (WTP) threshold of €80,000 per QALY was adopted. Sensitivity and scenario analyses were performed to address parameter uncertainty and to explore what parameters had the greatest impact on the cost-effectiveness results. RESULTS: PCI was more effective and costly (0.443 QALYs, €10,123) than no PCI, resulting in an incremental cost-effectiveness ratio (ICER) of €22,843 per QALY gained. The probability of PCI being cost-effective at a WTP threshold of €80,000 per QALY was 93%. The probability of PCI gaining three and six additional months of life were 76% and 56%. The scenario analysis adding durvalumab increased the ICER to €35,159 per QALY gained. Using alternative survival distributions had little impact on the ICER. Assuming fewer PCI fractions and excluding indirect costs decreased the ICER to €18,263 and €5554 per QALY gained. CONCLUSION: PCI is cost-effective compared to no PCI in stage III NSCLC, and could therefore, from a cost-effectiveness perspective, be considered in routine care.

Assessment of cellular and molecular changes in the rat brain after gamma radiation and radioprotection by anisomycin.

The objective of the study was to describe cellular and molecular markers of radioprotection by anisomycin, focusing on the changes in rat brain tissue. Two-month-old Wistar rats were exposed to a 60Co radiation source at a dose of 6 Gy, with or without radioprotection with anisomycin (150 mg/kg) administered subcutaneously 30 min before or 3 or 6 h after irradiation. Survivors were analyzed 30 days after treatment. Astroglial and microglial responses were investigated based on the expression of glial markers assessed with immunohistochemistry, and quantitative changes in brain biomolecules were investigated by Raman microspectroscopy. In addition, blood plasma levels of pro-inflammatory (interleukin 6 and tumor necrosis factor α) and anti-inflammatory (interleukin 10) cytokines were assessed. We found that application of anisomycin either before or after irradiation significantly decreased the expression of the microglial marker Iba-1. We also found an increased intensity of Raman spectral bands related to nucleic acids, as well as an increased level of cytokines when anisomycin was applied after irradiation. This suggests that the radioprotective effects of anisomycin are by decreasing Iba-1 expression and stabilizing genetic material by increasing the level of nucleic acids.

Cost-Effectiveness of Prophylactic Cranial Irradiation Versus MRI Surveillance for Extensive-Stage Small Cell Lung Cancer.

PURPOSE: Owing to conflicting prospective data, controversy exists regarding prophylactic cranial irradiation (PCI) in extensive-stage small cell lung cancer (ES-SCLC). We evaluated the cost-effectiveness of PCI versus magnetic resonance imaging (MRI) surveillance for patients with ES-SCLC based on currently available evidence and in the context of the proposed Centers for Medicare & Medicaid Services alternative payment model. METHODS AND MATERIALS: A Markov state transition model was constructed to perform a cost-effectiveness analysis comparing MRI surveillance alone with PCI for ES-SCLC. Clinical parameters were obtained from clinical trial data, and cost data were based on 2019 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with effectiveness in quality-adjusted life years (QALYs) and evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. One-way and probabilistic sensitivity analyses were performed to consider model uncertainty. RESULTS: In the base-case scenario, PCI was not cost-effective in this model, with an ICER of $168,456 per QALY gained compared with MRI surveillance alone, assuming that overall survival was 10 months for MRI surveillance alone and 12.5 months for PCI. One-way sensitivity analysis showed that results were most sensitive to the variation of overall survival and cognitive decline rates between the 2 groups. In a scenario analysis in which all patients received hippocampal-avoidance PCI, the model results became nearly cost-effective with PCI. CONCLUSIONS: PCI was not found to be cost-effective within this model compared with MRI surveillance alone, owing to the neurocognition decline effect of PCI based on available evidence. Hippocampal-avoidance PCI may be a potential cost-effective strategy for ES-SCLC, with confirmation expected after an ongoing prospective clinical trial (The Southwest Oncolology Group MRI Brain Surveillance Alone Versus MRI Surveillance And Prophylactic Cranial Irradiation [MAVERICK]), which includes assessments of cognitive function.

Cost-effectiveness of icotinib versus whole-brain irradiation with or without chemotherapy in EGFR-mutant NSCLC patients with brain metastases.

PURPOSE: Nonsmall cell lung cancer (NSCLC) patients with brain metastases (BM) have a poor prognosis. Despite the traditional methods including radiotherapy and chemotherapy, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) might benefit patients on survival and quality of life. We investigated the cost-effectiveness of icotinib compared with whole-brain irradiation (WBI) with or without chemotherapy for NSCLC patients with BM. MATERIALS AND METHODS: A Markov model was conducted based on the data of BRAIN trial. We compared the economic benefit between icotinib and the combination of WBI and WBI plus chemotherapy group. We considered disease progression as intracranial progression and overall progression separately. Sensitivity analyses were performed to observe the stability of the model. The willingness-to-pay (WTP) was set as 3× per capita gross domestic product ($25929/quality-adjusted life year [QALY]) from the Chinese healthcare perspective. RESULTS: When considering progression as intracranial progression and overall progression, respectively, the incremental cost-effectiveness ratio was $14 882.64/QALY and $13 484.21/QALY between icotinib and WBI/WBI-chemotherapy. Besides, both of the average cost-effective ratio (ACER) and net benefit showed advantage of icotinib (ACER: $34 521.42/QALY for intracranial progression and $36 562.63/QALY for overall progression; net benefit: -$8407.36 for intracranial progression and -$9836.41 for overall progression). One-way sensitivity analyses demonstrated that no thresholds were encountered. The probabilistic sensitivity analyses showed even at a WTP under $18 000/QALY, icotinib could be cost-effective. CONCLUSION: Icotinib was cost-effective compared with WBI with or without chemotherapy.

Assessment and Treatment Outcomes of Persistent Radiation-Induced Alopecia in Patients With Cancer.

Importance: Persistent radiation-induced alopecia (pRIA) and its management have not been systematically described. Objective: To characterize pRIA in patients with primary central nervous system (CNS) tumors or head and neck sarcoma. Design, Setting, and Participants: A retrospective cohort study of patients from January 1, 2011, to January 30, 2019, was conducted at 2 large tertiary care hospitals and comprehensive cancer centers. Seventy-one children and adults diagnosed with primary CNS tumors or head and neck sarcomas were evaluated for pRIA. Main Outcomes and Measures: The clinical and trichoscopic features, scalp radiation dose-response relationship, and response to topical minoxidil were assessed using standardized clinical photographs of the scalp, trichoscopic images, and radiotherapy treatment plans. Results: Of the 71 patients included (median [range] age, 27 [4-75] years; 51 female [72%]), 64 (90%) had a CNS tumor and 7 (10%) had head and neck sarcoma. Alopecia severity was grade 1 in 40 of 70 patients (56%), with localized (29 of 54 [54%]), diffuse (13 of 54 [24%]), or mixed (12 of 54 [22%]) patterns. The median (range) estimated scalp radiation dose was 39.6 (15.1-50.0) Gy; higher dose (odds ratio [OR], 1.15; 95% CI, 1.04-1.28) and proton irradiation (OR, 5.7; 95% CI, 1.05-30.8) were associated with greater alopecia severity (P < .001), and the dose at which 50% of patients were estimated to have severe (grade 2) alopecia was 36.1 Gy (95% CI, 33.7-39.6 Gy). Predominant trichoscopic features included white patches (16 of 28 [57%]); in 15 patients, hair-shaft caliber negatively correlated with scalp dose (correlation coefficient, -0.624; P = .01). The association between hair density and scalp radiation dose was not statistically significant (-0.381; P = .16). Twenty-eight of 34 patients (82%) responded to topical minoxidil, 5% (median follow-up, 61 [interquartile range, 21-105] weeks); 4 of 25 (16%) topical minoxidil recipients with clinical images improved in severity grade. Two patients responded to hair transplantation and 1 patient responded to plastic surgical reconstruction. Conclusions and Relevance: Persistent radiation-induced alopecia among patients with primary CNS tumors or head and neck sarcomas represents a dose-dependent phenomenon that has distinctive clinical and trichoscopic features. The findings of this study suggest that topical minoxidil and procedural interventions may have benefit in the treatment of pRIA.

Survival outcomes in an older US population with advanced melanoma and central nervous system metastases: SEER-Medicare analysis.

BACKGROUND: Central nervous system (CNS) metastasis is common in advanced melanoma patients. New treatment options have improved overall prognosis, but information is lacking for patients with CNS metastases. We investigated treatment patterns and survival outcomes in older melanoma patients with and without CNS metastases. METHODS: A retrospective analysis of SEER-Medicare, a population-based linked database, was undertaken in patients aged > 65 years with advanced melanoma diagnosed from 2004 to 2011 and followed until 2013. RESULTS: A total of 2522 patients were included. CNS metastases were present in 24.8% of patients at initial metastatic diagnosis; 16.5% developed CNS metastases during follow-up. Chemotherapy was the most common treatment regardless of CNS metastases. Overall survival (OS) was better for patients without CNS metastases (median, 9.5 months; 95% confidence interval [CI], 8.8-10.2) vs patients with CNS metastases (3.63 months; 95% CI, 3.4-3.9). Among patients with CNS metastases, median OS for targeted therapy, immunotherapy, and chemotherapy was 6 (95% CI, 2.5-9.6), 5.5 (95% CI, 3.8-7.5), and 4.5 (95% CI, 3.8-5.4) months, respectively, vs 2.4 (95% CI, 2.1-2.7) and 2.1 (95% CI, 1.8-2.7) months for local radiotherapy and no treatment, respectively. Stereotactic radiosurgery demonstrated higher OS vs whole-brain radiation therapy (median, 4.98 [95% CI, 3.5-7.5] vs 2.4 [95% CI, 2.1-2.7] months). CONCLUSION: Patients with CNS metastases from melanoma remain a population with high unmet medical need despite recent advances in treatment. Systemic treatments (eg, BRAF-targeted therapy and immunotherapy) and stereotactic radiosurgery demonstrated meaningful but modest improvements in OS. Further explorations of combinations of radiotherapy, BRAF-targeted therapies, and immunotherapies are needed.

Brain Metastases From Gynecologic Malignancies: Prevalence and Management.

OBJECTIVE: The objective of this study was to investigate the prevalence, clinicopathologic characteristics, management, and outcomes of patients with brain metastasis (BM) from gynecologic malignancies in a large hospital-based database. MATERIALS AND METHODS: The National Cancer Database (NCDB) was accessed and patients with ovarian, uterine, or cervical cancer and BM were identified. We identified those who received radiation therapy (RT) as whole-brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Kaplan-Meier curves were generated to determine median overall survival (OS) and compared with the log-rank test. RESULTS: A total of 853 patients with BM were identified. The rate of BMs upon diagnosis was 0.4% (211/57,160) for patients with cervical cancer, 0.2% (498/243,785) for patients with uterine, and 0.2% (144/92,301) for ovarian malignancies. Only 30.4% had isolated BM, while 52.2% had lung metastasis. Approximately half of the patients (50.1%) received chemotherapy, while brain RT was administered to 324 (38%) patients. Among patients who received brain RT, only 60 (18.5%) had SRS, while 264 (81.5%) had WBRT. Patients who underwent SRS had a better survival (n=47, median OS=9 mo) than those who received WBRT (n=201, median OS=4.73 mo, P=0.018), or those who did not receive any brain RT (n=370, median OS=4.01 mo, P=0.007). CONCLUSIONS: The incidence of BM among patients with gynecologic malignancies is rare and associated with poor survival. For select patients, SRS may be associated with prolonged survival.

Among Individuals Irradiated for Benign Conditions in Childhood, Developing Thyroid Cancer Does Not Affect All-Cause Survival.

Background: Whether radiation-induced thyroid cancer affects survival rates has not been clearly elucidated. Survival could be affected by the thyroid cancer itself, its treatment, or by being a sign of susceptibility to other cancers. The objective of the current study was to determine if the development of thyroid cancer is associated with a differential survival in radiation-exposed individuals. Methods: We conducted a matched prospective cohort mortality follow-up study based on data from a cohort of 4296 individuals who were irradiated predominantly for enlarged tonsils during their childhood (between 1939 and 1962) and were prospectively followed since 1974. The study matched an irradiated subject who developed (was exposed to) thyroid cancer (a "case") and two irradiated subjects, who had not developed (were not exposed to) thyroid cancer ("controls") by the time of case incidence. The two controls were randomly matched to cases by sex, year of birth, age at radiation treatment, and radiation dose. Then, using a stratified Cox analysis, we compared survival time from the date of thyroid cancer diagnosis or time of selection to either date of death or the end of the observation period (December 31, 2016). Vital status and causes of death were determined using the National Death Index (1979-2016), the Social Security Death Index (1974-1979), and study files. Cause of death was categorized as cardiovascular, malignancy, or other. Results: A total of 1008 subjects were included in the analysis, including 353 thyroid cancer cases. At the end of the study period, 162 of 655 (24.7%) of individuals without thyroid cancer had died compared with 100 of 353 (28.3%) of the subjects with thyroid cancer. The hazard ratio (HR) for all-cause mortality, comparing the thyroid cancer cases to controls, was close to unity (HR = 1.01 [0.77-1.33]). HRs remained insignificant after eliminating matched sets with microcarcinomas, defined as tumor size <10 mm (HR = 1.39 [0.96-2.03]). Distribution of the causes of death taking into account age and the time of observation differed between cases and controls (p < 0.05). Neither increased cardiovascular-related nor malignancy-related mortality was associated with radiation-induced thyroid cancer. Conclusions: Among individuals irradiated for benign conditions in childhood, development of thyroid cancer was not associated with decreased all-cause survival.

Whole-brain radiotherapy plus sequential or simultaneous integrated boost for the treatment of a limited number of brain metastases in non-small cell lung cancer: A single-institution study.

BACKGROUND: To compare the survival outcomes and neurocognitive dysfunction in non-small cell lung cancer (NSCLC) patients with brain metastases (BM ≤10) treated by whole-brain radiotherapy (WBRT) with sequential integrated boost (SEB) or simultaneous integrated boost (SIB). MATERIALS: Fifty-two NSCLC patients with a limited number of BMs were retrospectively analyzed. Twenty cases received WBRT+SEB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*3 fractions; SEB group), and 32 cases received WBRT+SIB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*10 fractions; SIB group). The survival and mini-mental state examination (MMSE) scores were compared between the groups. RESULTS: The cumulative 1-, 2-, and 3-year survival rates in the SEB vs SIB groups were 60.0% vs 47.8%, 41.1% vs 19.1%, and 27.4% vs 0%, respectively. The median survival times in the SEB and SIB groups were 15 and 10 months, respectively. The difference in survival rate was significant (P = .046). Subgroup analysis revealed that 1-, 2-, and 3-year survival rates and median survival time in the SEB group were significantly superior to those of the SIB group, especially for male patients (age <60 years) with 1-2 BMs (P < .05). The MMSE score of the SEB group at 3 months after radiation was higher than that of the SIB group (P < .05). Nevertheless, WBRT+SEB required a longer treatment time and greater cost (P < .005). CONCLUSIONS: WBRT + SEB results in better survival outcomes than WBRT+SIB, especially for male patients (age <60 years) with 1-2 BMs. WBRT+SEB also appeared to induce less neurocognitive impairment than WBRT+SIB.

Longitudinal cognitive assessment in patients with primary CNS lymphoma treated with induction chemotherapy followed by reduced-dose whole-brain radiotherapy or autologous stem cell transplantation.

INTRODUCTION: The standard treatment for primary central nervous system lymphoma (PCNSL) involves induction methotrexate-based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). As WBRT carries a substantial risk for cognitive impairment, alternative consolidation treatments have been used to reduce neurotoxicity, including reduced-dose WBRT (rdWBRT) or high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT). In this study, we characterized cognitive functions in PCNSL patients achieving long-term remission following rdWBRT or HDC-ASCT. METHODS: PCNSL patients completed cognitive evaluations at diagnosis, post-induction chemotherapy, and yearly up to 5 years following rdWBRT or HDC-ASCT. Quality of life (QoL), white matter (WM) disease, and cortical atrophy (CA) on MRI were assessed at similar intervals. RESULTS: Performance was impaired on most cognitive tests at diagnosis. Linear mixed model analyses in each group showed statistically significant improvement from baseline up to year 3 in attention/executive functions, graphomotor speed, and memory; however, there was a decline in attention/executive functions and memory after year 3 in both groups. WM abnormalities increased over time in both groups, but more patients treated with rdWBRT developed CA and WM changes. There were no significant longitudinal group differences in cognitive performance or QoL. CONCLUSIONS: Results indicated improvement in cognitive function up to 3 years post-treatment, but a decline at later time points and an increase in brain structure abnormalities in both groups. The findings suggest that rdWBRT and HDC-ASCT may be associated with delayed neurotoxicity in progression-free patients and underscore the need for long-term follow-up to characterize cognitive dysfunction in PCNSL patients.

Comparing survival predicted by the diagnosis-specific Graded Prognostic Assessment (DS-GPA) to actual survival in patients with 1-10 brain metastases treated with stereotactic radiosurgery.

BACKGROUND AND PURPOSE: Multiple prognostic models for predicting survival after treatment for brain metastases have been developed. One of them, the diagnosis-specific Graded Prognostic Assessment (DS-GPA), has been developed to predict the median survival for brain metastases from the most frequent primary sites: lung carcinoma, breast cancer, melanoma, renal cell cancer and gastrointestinal tumours. In this study we aim to compare the survival predicted by the DS-GPA to actual survival, and to assess this models performance on both population and individual levels. METHODS: We identified a consecutive cohort of patients treated with SRS for brain metastases in our institute. DS-GPA scores were calculated for each patient, and the median survival for each DS-GPA group was calculated. Differences in survival between DS-GPA groups were tested with Wilcoxon Signed Rank tests and log-rank tests. RESULTS: In total 367 patients were included in the analysis. Median survival in our cohort is largely comparable to corresponding DS-GPA cohorts, but some notable differences are present. There was a significantly shorter median survival (15.4 months, compared to 26.5 months) in the adenocarcinoma NSCLC subgroup with a GPA score of 2.3-3. We confirmed the significant differences in survival time for most cancer-specific subgroups. CONCLUSION: DS-GPA seems to be a reliable tool to classify patients with brain metastases treated with SRS into prognostic subgroups. However, we found some aberrations from predicted median survival times, which may be due to specific characteristics of the populations of patients treated with SRS versus other patients.

Prospective Assessment of Patient-Reported Dry Eye Syndrome After Whole Brain Radiation.

PURPOSE: Dry eye is not typically considered a toxicity of whole brain radiation therapy (WBRT). We analyzed dry eye syndrome as part of a prospective study of patient-reported outcomes after WBRT. METHODS AND MATERIALS: Patients receiving WBRT to 25 to 40 Gy were enrolled on a study with dry mouth as the primary endpoint and dry eye syndrome as a secondary endpoint. Patients received 3-dimensional WBRT using opposed lateral fields. Per standard practice, lacrimal glands were not prospectively delineated. Patients completed the Subjective Evaluation of Symptom of Dryness (SESoD, scored 0-4, with higher scores representing worse dry eye symptoms) at baseline, immediately after WBRT (EndRT), and at 1 month (1M), 3 months, and 6 months. Patients with baseline SESoD ≥3 (moderate dry eye) were excluded. The endpoints analyzed were ≥1-point and ≥2-point increase in SESoD score at 1M. Lacrimal glands were retrospectively delineated with fused magnetic resonance imaging scans. RESULTS: One hundred patients were enrolled, 70 were eligible for analysis, and 54 were evaluable at 1M. Median bilateral lacrimal V20Gy was 79%. At 1M, 17 patients (32%) had a ≥1-point increase in SESoD score, and 13 (24%) a ≥2-point increase. Lacrimal doses appeared to be associated with an increase in SESoD score of both ≥1 point (V10Gy: P = .042, odds ratio [OR] 1.09/%; V20Gy: P = .071, OR 1.03/%) and ≥2 points (V10Gy: P = .038, OR 1.15/%; V20Gy: P = .063, OR 1.04/%). The proportion with increase in dry eye symptoms at 1M for lacrimal V20Gy ≥79% versus <79% was 46% versus 15%, respectively, for ≥1 point SESoD increase (P = .02) and 36% versus 12%, respectively, for ≥2 point SESoD increase (P = .056). CONCLUSIONS: Dry eye appears to be a relatively common, dose/volume-dependent acute toxicity of WBRT. Minimization of lacrimal gland dose may reduce this toxicity, and patients should be counseled regarding the existence of this potential side effect and treatments for dry eye.

Efficacy and toxicity of particle radiotherapy in WHO grade II and grade III meningiomas: a systematic review.

OBJECTIVEAdjuvant radiotherapy has become a common addition to the management of high-grade meningiomas, as immediate treatment with radiation following resection has been associated with significantly improved outcomes. Recent investigations into particle therapy have expanded into the management of high-risk meningiomas. Here, the authors systematically review studies on the efficacy and utility of particle-based radiotherapy in the management of high-grade meningioma.METHODSA literature search was developed by first defining the population, intervention, comparison, outcomes, and study design (PICOS). A search strategy was designed for each of three electronic databases: PubMed, Embase, and Scopus. Data extraction was conducted in accordance with the PRISMA guidelines. Outcomes of interest included local disease control, overall survival, and toxicity, which were compared with historical data on photon-based therapies.RESULTSEleven retrospective studies including 240 patients with atypical (WHO grade II) and anaplastic (WHO grade III) meningioma undergoing particle radiation therapy were identified. Five of the 11 studies included in this systematic review focused specifically on WHO grade II and III meningiomas; the others also included WHO grade I meningioma. Across all of the studies, the median follow-up ranged from 6 to 145 months. Local control rates for high-grade meningiomas ranged from 46.7% to 86% by the last follow-up or at 5 years. Overall survival rates ranged from 0% to 100% with better prognoses for atypical than for malignant meningiomas. Radiation necrosis was the most common adverse effect of treatment, occurring in 3.9% of specified cases.CONCLUSIONSDespite the lack of randomized prospective trials, this review of existing retrospective studies suggests that particle therapy, whether an adjuvant or a stand-alone treatment, confers survival benefit with a relatively low risk for severe treatment-derived toxicity compared to standard photon-based therapy. However, additional controlled studies are needed.

Determining the role of adjuvant radiotherapy in the management of meningioma: a Surveillance, Epidemiology, and End Results analysis.

OBJECTIVEThe aim of this study was to illustrate the demographic characteristics of meningioma patients and observe the effect of adjuvant radiation therapy on survival by using the Surveillance, Epidemiology, and End Results (SEER) database. More specifically, the authors aimed to answer the question of whether adjuvant radiotherapy following resection of atypical meningioma confers a cause-specific survival benefit. Additionally, they attempted to add to previous characterizations of the epidemiology of primary meningiomas and assess the effectiveness of the standard of care for benign and anaplastic meningiomas. They also sought to characterize the efficacy of various treatment options in atypical and anaplastic meningiomas separately since nearly all other analyses have grouped these two together despite varying treatment regimens for these behavior categories.METHODSSEER data from 1973 to 2015 were queried using appropriate ICD-O-3 codes for benign, atypical, and anaplastic meningiomas. Patient demographics, tumor characteristics, and treatment choices were analyzed. The effects of treatment were examined using a multivariate Cox proportional hazards model and Kaplan-Meier survival analysis.RESULTSA total of 57,998 patients were included in the analysis of demographic, meningioma, and treatment characteristics. Among this population, cases of unspecified WHO tumor grade were excluded in the multivariate analysis, leaving a total of 12,931 patients to examine outcomes among treatment paradigms. In benign meningiomas, gross-total resection (HR 0.289, p = 0.013) imparted a significant cause-specific survival benefit over no treatment. In anaplastic meningioma cases, adjuvant radiotherapy imparted a significant survival benefit following both subtotal (HR 0.089, p = 0.018) and gross-total (HR 0.162, p = 0.002) resection as compared to gross-total resection alone. In atypical tumors, gross-total resection plus radiotherapy did not significantly change the hazard risk (HR 1.353, p = 0.628) compared to gross-total resection alone. Similarly, it was found that adjuvant radiation did not significantly benefit survival after a subtotal resection (HR 1.440, p = 0.644).CONCLUSIONSThe results of this study demonstrate that the role of adjuvant radiotherapy, especially after the resection of atypical meningioma, remains somewhat unclear. Thus, given these results, prospective randomized clinical studies are warranted to provide clear information on the effects of adjuvant radiation in meningioma treatment.

Effect of photobiomodulation on the severity of oral mucositis and molecular changes in head and neck cancer patients undergoing radiotherapy: a study protocol for a cost-effectiveness randomized clinical trial.

BACKGROUND: Oral mucositis (OM) is the most frequent and debilitating acute side effect associated with head and neck cancer (HNC) treatment. When present, severe OM negatively impacts the quality of life of patients undergoing HNC treatment. Photobiomodulation is a well-consolidated and effective therapy for the treatment and prevention of severe OM, and is associated with a cost reduction of the cancer treatment. Although an increase in the quality of life and a reduction in the severity of OM are well described, there is no study on cost-effectiveness for this approach considering the quality of life as a primary outcome. In addition, little is known about the photobiomodulation effects on salivary inflammatory mediators. Thus, this study aimed to assess the cost-effectiveness of the photobiomodulation therapy for the prevention and control of severe OM and its influence on the salivary inflammatory mediators. METHODS/DESIGN: This randomized, double-blind clinical trial will include 50 HNC patients undergoing radiotherapy or chemoradiotherapy. The participants will be randomized into two groups: intervention group (photobiomodulation) and control group (preventive oral care protocol). OM (clinical assessment), saliva (assessment of collected samples) and quality of life (Oral Health Impact Profile-14 and Patient-Reported Oral Mucositis Symptoms questionnaires) will be assessed at the 1st, 7th, 14th, 21st and 30th radiotherapy sessions. Oxidative stress and inflammatory cytokine levels will be measured in the saliva samples of all participants. The costs are identified, measured and evaluated considering the radiotherapy time interval. The incremental cost-effectiveness ratio will be estimated. The study will be conducted according to the Brazilian public health system perspective. DISCUSSION: Photobiomodulation is an effective therapy that reduces the cost associated with OM treatment. However, little is known about its cost-effectiveness, mainly when quality of life is the effectiveness measure. Additionally, this therapy is not supported by the Brazilian public health system. Therefore, this study widens the knowledge about the safety of and strengthens evidence for the use of photobiomodulation therapy, providing information for public policy-makers and also for dental care professionals. This study is strongly encouraged due to its clinical relevance and the possibility of incorporating new technology into public health systems. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials-ReBEC, RBR-5h4y4n . Registered on 13 June 2017.