Omission of Axillary Lymph Node Dissection is Associated with Inferior Survival in Breast Cancer Patients with Residual N1 Nodal Disease Following Neoadjuvant Chemotherapy.

BACKGROUND: The appropriateness of substituting sentinel lymph node dissection (SLND) and regional nodal irradiation (RNI) for axillary lymph node dissection (ALND) in patients with residual lymph node (LN) disease following neoadjuvant chemotherapy (NAC) is unknown. We used the National Cancer Database (NCDB) to compare survival following SLND and ALND in breast cancer patients with residual LN disease. METHODS: We analyzed NCDB patients, treated between 2006 and 2014, with cT1-3, cN1, cM0 breast cancer and residual disease in 1-3 axillary LNs (ypN1) following NAC. Patients were grouped into those who received SLND (defined as removal of ≤ 4 LNs) and RNI, or ALND and RNI. Patients were matched for all patient, tumor, and treatment characteristics. RESULTS: We identified 1313 eligible patients in the ALND group and 304 patients in the SLND group. For the matched cohorts, SLND was associated with significantly lower survival in both univariate and doubly robust multivariable analyses (MVA) (HR 1.7, 95% CI 1.3-2.2, P < 0.001 for MVA), with estimated 5-year OS of 71%, compared with 77% in the ALND group (P = 0.01). Exploratory subgroup analyses showed that SLND was comparable with ALND in patients with luminal A or B tumors with a single metastatic LN (HR 1.03, 95% CI 0.59-1.8, (P = 0.91). CONCLUSIONS: Our analysis suggests that, while an ALND may not be needed for patients with limited residual nodal burden and biologically favorable tumors, SLND should not be routinely substituted for ALND in patients with ypN1 disease following NAC until its efficacy is confirmed by prospective trials.

Trimodality therapy for atypical teratoid/rhabdoid tumor is associated with improved overall survival: A surveillance, epidemiology, and end results analysis.

BACKGROUND: Atypical teratoid/rhabdoid tumors (AT/RTs) are rare aggressive central nervous system tumors. The use of radiation therapy (RT) remains controversial, especially for patients younger than three years of age. The purpose of the current investigation is to robustly analyze the impact of RT among pediatric AT/RT patients using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: SEER 18 Custom Data registries were queried for AT/RT (ICD-0-3 9508/3). A total of 190 pediatric AT/RT patients were identified, of whom 102 underwent surgery + chemotherapy and 88 underwent trimodality therapy. Univariate and multivariable analyses using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting was performed to account for indication bias. The landmark method was used to account for immortal time bias. RESULTS: The majority of patients were <3 years old (75.8%). Patients <3 were more likely to be treated without RT as compared with older patients (62% vs 38%). Doubly robust MVA identified distant disease as a negative prognostic factor (HR 2.1, P = 0.003), whereas trimodality therapy was strongly protective (HR 0.39, P < 0.001). Infants (<1), toddlers (1-2), and older children (3+) all benefited from trimodality therapy, with largest benefit for infants (HR 0.34, P = 0.02) and toddlers (HR 0.31, P < 0.001). CONCLUSION: The current study provides further evidence that trimodality therapy improves clinical outcomes among patients with AT/RT. This finding was most pronounced for younger patients; therefore, further studies are needed to confirm this finding in this vulnerable population.

The role of betel-quid chewing in smoking cessation among workers in Taiwan.

BACKGROUND: Current smokers exhibit a higher rate of betel-quid chewing than non-smokers. However, little is known regarding the extent to which betel-quid chewing may affect attempts to quit smoking and smoking cessation. The aim of the present study is to examine the association between betel-quid chewing and patterns of quitting smoking. Specifically, we explore whether betel-quid chewing is associated with (1) current smokers who have never attempted to quit versus those who have attempted to quit and have failed, those who are in the process of quitting, and successful cessation smokers, and (2) current smokers who have attempted to quit and have failed versus those who have successfully quit smoking. METHODS: A telephone survey of 7,215 workers was conducted and obtained an 88.6% response rate. In the survey, the respondents' smoking and betel-quid chewing statuses were recorded and a list of covariates was assessed. RESULTS: After controlling for the effect of the covariates, betel-quid chewing was found to be more highly associated with current smokers who have never attempted to quit, compared to current smokers who are in the process of quitting (OR = 12.72; 95% CI = 1.05-154.26), successful cessation smokers (OR = 3.62; 95% CI = 2.32-5.65), and smokers who have attempted to quit and have failed (OR = 1.37; 95% CI = 1.06-1.77), respectively. In addition, betel-quid chewing is more highly associated with a failure to quit smoking than with successfully quitting smoking (OR = 3.46; 95% CI = 2.17-5.51). CONCLUSION: The findings support four plausible reasons why betel-quid chewing may dissuade smokers from quitting. These reasons highlight additional avenues for potentially reducing the smoking population in workplaces, such as considering work contexts and social norms, and product sales in smoking-cessation campaigns.

The potential role of meaning in life in the relationship between bullying victimization and suicidal ideation.

Adolescent bullying is a common problem in schools across America. The consequences of bullying are significant, and can include severe psychological trauma and suicide. A better understanding of the mechanisms that link bullying and suicidal ideation is needed in order to develop effective prevention and intervention initiatives. Meaning in life is a potential mechanism that has not been studied in this context. It was hypothesized that meaning in life could serve as both a mediator and a moderator of the relationship between bullying victimization and suicidal ideation. As a mediator, meaning in life is considered to explain why bullying victimization leads to suicidal ideation. As a moderator, meaning in life is considered to buffer the ill effect of bullying victimization on suicidal ideation. Data collected from an ethnically diverse sample of 2,936 (50% female), 6th-12th grade students from one urban school district in the Northeastern US were used to examine the hypotheses. The model for girls was consistent with mediation (i.e., meaning in life may explain how victimization leads to suicidal ideation). The model for boys was consistent with moderation (i.e., the ill effect of victimization on suicidal ideation was attenuated as meaning in life increased). Implications for prevention are discussed.

Breast Irradiation Is Well Tolerated in Carriers of a Pathogenic ATM Variant.

PURPOSE: There are mixed and limited data regarding radiation therapy (RT) tolerance in carriers of a germline pathogenic or likely pathogenic (P/LP) ATM variant. We investigated RT-related toxic effects in carriers of an ATM variant who received treatment for breast cancer. METHODS AND MATERIALS: We identified 71 patients treated with adjuvant RT for breast cancer who were carriers of a variant in ATM: 15 were classified as P/LP and 56 classified as variants of unknown significance (VUS). We additionally identified 205 consecutively treated patients during a similar timeframe who were either confirmed ATM wild type or had no prior genetic testing. RT plans were reviewed. Acute and chronic toxic effects were evaluated using Common Terminology Criteria for Adverse Events version 4.0 criteria. Fisher's exact tests for count data were performed to compare toxic effects between the cohorts (P/LP vs VUS vs control). Wilcoxon rank-sum testing was performed to assess for differences in patient characteristics. RESULTS: The median toxicity follow-up was 19.4 months; median follow-up for the subcohorts was 13.3 months (P/LP), 12.6 months (VUS), and 23.3 months (control). There were no significant differences in radiation plan heterogeneity, receipt of a boost, or size of breast/chest wall planning target volume. There was greater use of hypofractionated RT in the control cohort (P = .023). After accounting for patient- and treatment-related factors that may affect toxic effects, we found no significant differences with respect to acute dermatitis, hyperpigmentation, moist desquamation, breast/chest wall pain, or breast edema. Additionally, we found no significant differences with respect to chronic breast/chest wall pain, induration, telangiectasia, or cosmetic outcome. CONCLUSIONS: RT as part of the management of breast cancer was well tolerated in carriers of a P/LP ATM variant, with toxic effect profiles that were similar to those seen in patients without known ATM mutations. High rates of excellent or good cosmesis were observed in carriers of a P/LP ATM variant who underwent breast conservation.

Clinical Outcomes of Breast-Conserving Surgery with Synchronous 50-kV X-ray Intraoperative Partial Breast Irradiation in Patients Aged 64 Years or Older with Low-Risk Breast Cancer.

Background: Breast-conserving surgery with synchronous 50-kV X-ray intraoperative radiation therapy (TARGIT-IORT) is a convenient form of partial breast irradiation; however, the existing literature supports a wide range of local control rates. Objectives: We investigated the treatment effectiveness and toxic effects of TARGIT-IORT in a patient cohort aged 64 years or older with low-risk breast cancer. Design: Retrospective analysis. Methods: Patients who received breast-conserving surgery with synchronous TARGIT-IORT at a single institution from 2016 to 2019 were reviewed. Additional whole breast irradiation was recommended at the discretion of the treating radiation oncologist. Baseline patient demographics and treatment details were recorded. Acute and chronic toxicities, measured using the Common Terminology Criteria for Adverse Events version 3.0 or 4.0 and breast cosmetic outcomes, using the Harvard Cosmesis score, were recorded. Locoregional recurrence, distant metastasis, and overall survival were recorded, and 5-year rates were estimated using the Kaplan-Meier method. Results: 61 patients were included with a median follow-up of 3.5 years and median age of 72 years. Eight (13%) patients received additional whole breast irradiation, and fifty-four (89%) received adjuvant hormone therapy. There were no local, regional, or distance recurrences. One patient died of complications from COVID-19 infection. Grade 2 + acute and chronic toxicities were observed in 6 (12%) and 7 (14%) patients, respectively. One patient experienced a grade 3 acute toxicity. Cosmetic outcome was "excellent" or "good" in 45 (92%) patients. Conclusions: Breast TARGIT-IORT was well tolerated and conferred excellent disease control in this cohort of patients with low-risk breast cancer. While continued follow-up is required, TARGIT-IORT may be an appropriate treatment option for this population.

Long-term impact of young age at diagnosis on treatment outcome and patterns of failure in patients with ductal carcinoma in situ treated with breast-conserving therapy.

We reviewed our institution's long-term experience treating patients diagnosed with ductal carcinoma in situ (DCIS) of the breast with breast-conserving therapy (BCT) to determine the impact of patient age on outcome over time. All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics (including age <45) and pathologic factors were analyzed for effect on outcomes including ipsilateral breast tumor recurrence (IBTR) and survival. BCT included limited surgery (excisional biopsy or lumpectomy) followed by radiotherapy to the whole breast (median whole-breast dose: 50 Gy, median tumor bed dose: 60.4 Gy). One hundred and forty-five cases were evaluated; the median follow-up was 19.3 years. Twenty-five patients developed an IBTR, for 5-, 10-, 15-, and 20-year actuarial rates of 9.9%, 12.2%, 13.7%, and 17.5%, respectively. The 10-year ipsilateral rate of recurrence was 23.3% (<45 years) versus 9.1% (≥ 45 years) (p = 0.05). Younger patients more frequently developed invasive recurrences (20-year actuarial rates: 20.4% versus 12.8%, p = 0.22) and true recurrences/marginal misses of the index lesion (23.3% versus 9.7%, p = 0.04) with lower rates of contralateral breast cancer (0.0% and 0.0% versus 12.0% and 20.5%, p = < 0.01, at 10 and 20 years, respectively). Young women under the age of 45 diagnosed with DCIS have a greater risk of local recurrence with different patterns of failure following BCT, which is most notable within 10 years of diagnosis.

Construction workers' reasons for not reporting work-related injuries: an exploratory study.

Although under-reporting of work-related injuries by workers is recognized as a significant problem in construction and other industries, little is known about the specific reasons for such occurrences. Qualitative and quantitative methods were used in this study to (a) identify reasons why construction workers may choose not to report work-related injuries, and (b) to investigate the frequency of the identified reasons. Twenty-seven percent of a sample of construction workers (N = 135) indicated that they had failed to report a work-related injury. The most frequent reasons given were related to perceptions of injuries as "small" and "part of the job" as well as fear of negative consequences, which may follow injury reporting. These findings are discussed in terms of practical implications. Strategies to overcome these reasons are suggested to decrease the under-reporting of injuries in the construction industry.

Near-Surface Dose Correlates With Moist Desquamation and Unplanned Reconstructive Surgery in Patients With Implant-Based Reconstruction Receiving Postmastectomy Radiation Therapy.

Purpose: Postmastectomy radiation therapy (PMRT) reduces disease recurrence in appropriately selected patients but may compromise implant-based reconstruction. We investigated whether near-surface dose correlates with radiation-related toxic effects in these patients. Methods and Materials: Patients receiving PMRT at a single institution from 2016 to 2019 were retrospectively reviewed. Patient demographics and treatment information were collected. Three near-surface structures were retrospectively generated, bound by the chest wall tangent beam as well as the skin surface and the skin-3 mm contour (SR3), skin surface and skin-5 mm contour (SR5), or skin-5 and skin-10 mm contours. Dosimetric analysis of these near-surface contours was performed in 2 Gy intervals. Univariate and multivariate analyses were used to identify predictors of moist desquamation, grade 2+ chest wall pain, use of opiate pain medication, unplanned reconstructive surgery, and implant failure. Logistic regression for each outcome and near-surface contour was performed for receiver-operator area under the curve (AUC) analysis and the Youden J Statistic was used to determine the optimal threshold for each dosimetric parameter. Results: Of 126 patients reviewed, 109 met the study's eligibility criteria. Median follow-up was 2.3 years. Twenty-five patients (23%) underwent unplanned reconstructive surgery, and 10 (9.2%) experienced implant failure. Among clinical variables, low body mass index and history of smoking predicted unplanned surgery on univariate and multivariate analyses, and moist desquamation predicted grade 2+ chest wall pain. The top dosimetric parameters by AUC for moist desquamation, grade 2+ chest wall pain, use of opiates, unplanned reconstructive surgery, and implant failure were SR5 D10 cc (AUC = 0.701, optimal threshold 57.8 Gy, P < .001), SR3 D10 cc (AUC = 0.600, optimal threshold 56.8 Gy, P = .079), SR5 D10 cc (AUC = 0.642, optimal threshold 57.3 Gy, P = .041), SR3 V44 Gy (AUC = 0.711, optimal threshold 81%, P = .001), and SR3 V44 Gy (AUC = 0.688, optimal threshold 82%, P = .052), respectively. Conclusions: Near-surface dose correlates with moist desquamation and unplanned reconstructive surgery after PMRT. Further evaluation of prospective optimization of dosimetric parameters related to SR3 and SR5 should be considered.

Twenty-year outcomes after breast-conserving surgery and definitive radiotherapy for mammographically detected ductal carcinoma in situ.

BACKGROUND: Management of mammographically detected ductal carcinoma in situ (DCIS) at a single institution was reviewed to determine long-term clinical outcomes after treatment with breast-conserving therapy (BCT). METHODS: Data from all patient-cases with DCIS who received BCT between 1980 and 1993 were reviewed. Patient demographics and pathologic factors were analyzed for their effect on outcomes, including ipsilateral breast tumor recurrence (IBTR) and survival. BCT included breast-conserving surgery followed by external-beam radiotherapy to the whole breast, with 86 % of patients receiving a lumpectomy cavity boost. The median dose to the whole breast was 50 Gy and 60.4 Gy to the lumpectomy cavity. RESULTS: A total of 129 cases were evaluated; the median follow-up was 19.3 years. Twenty-one patients developed an ipsilateral breast tumor recurrence (IBTR), 76.2 % of which were invasive (n = 16). Fourteen recurrences (66 %) were within the same breast quadrant (true recurrence), while an additional 7 cases developed an IBTR elsewhere in the breast. True recurrences were more prevalent in women <45 years of age (20 %/24 % vs. 5.1 %/8 %) at 10 and 20 years (p = 0.02). The 5-, 10-, 15-, and 20-year actuarial rates of IBTR for this cohort were 8.7, 10.4, 12.1, and 16.3 % (IBTR), while overall survival at 5, 10, and 20 years was 97.6, 96.8, and 96.8 %, respectively. CONCLUSIONS: Mammographically detected DCIS remains a clinically distinct subset of noninvasive breast cancer. With 20 year follow-up, local control and overall survival are excellent after BCT.

Development and Validation of an Integrated Healthy Workplace Management Model in Taiwan.

Background: Impacts of exposure are generally monitored and recorded after injuries or illness occur. Yet, absence of conventional after-the-effect impacts (i.e., lagging indicators), tend to focus on physical health and injuries, and fail to inform if workers are not exposed to safety and health hazards. In contrast to lagging indicators, leading indicators are proactive, preventive, and predictive indexes that offer insights how effective safety and health. The present study is to validate an extended Voluntary Protection Programs (VPP) that consists of six leading indicators. Methods: Questionnaires were distributed to 13 organizations (response rate = 93.1%, 1,439 responses) in Taiwan. Cronbach α, multiple linear regression and canonical correlation were used to test the reliability of the extended Voluntary Protection Programs (VPP) which consists of six leading indicators (safe climate, transformational leadership, organizational justice, organizational support, hazard prevention and control, and training). Criteria-related validation strategy was applied to examine relationships of six leading indicators with six criteria (perceived health, burnout, depression, job satisfaction, job performance, and life satisfaction). Results: The results showed that the Cronbach's α of six leading indicators ranged from 0.87 to 0.92. The canonical correlation analysis indicated a positive correlation between the six leading indicators and criteria (1st canonical function: correlation = 0.647, square correlation = 0.419, p < 0.001). Conclusions: The present study validates the extended VPP framework that focuses on promoting safety and physical and mental health. Results further provides applications of the extended VPP framework to promote workers' safety and health.

Workplace bullying as an organizational problem: Spotlight on people management practices.

Though workplace bullying is conceptualized as an organizational problem, there remains a gap in understanding the contexts in which bullying manifests-knowledge vital for addressing bullying in practice. In three studies, we leverage the rich content contained within workplace bullying complaint records to explore this issue then, based on our discoveries, investigate people management practices linked to bullying. First, through content analysis of 342 official complaints lodged with a state health and safety regulator (over 5,500 pages), we discovered that the risk of bullying primarily arises from ineffective people management in 11 different contexts (e.g., managing underperformance, coordinating working hours, and entitlements). Next, we developed a behaviorally anchored rating scale to measure people management practices within a refined set of nine risk contexts. Effective and ineffective behavioral indicators were identified through content analysis of the complaints data and data from 44 critical incident interviews with subject matter experts; indicators were then sorted and rated by two independent samples to form a risk audit tool. Finally, data from a multilevel multisource study of 145 clinical healthcare staff nested in 25 hospital wards showed that the effectiveness of people management practices predicts concurrent exposure to workplace bullying at individual level beyond established organizational antecedents, and at the team level beyond leading indicator psychosocial safety climate. Overall, our findings highlight where the greatest risk of bullying lies within organizational systems and identifies effective ways of managing people within those contexts to reduce the risk, opening new avenues for bullying intervention research and practice. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Dose to the Left Anterior Descending Artery Correlates With Cardiac Events After Irradiation for Breast Cancer.

PURPOSE: Although global heart dose has been associated with late cardiac toxic effects in patients who received radiation therapy for breast cancer, data detailing the clinical significance of cardiac substructure dosimetry are limited. We investigated whether dose to the left anterior descending artery (LAD) correlates with adverse cardiac events. METHODS AND MATERIALS: We identified 375 consecutively treated female patients from 2012 to 2018 who received left-sided breast or chest wall irradiation (with or without regional nodal irradiation). Medical records were queried to identify cardiac events after radiation therapy. Mean and maximum LAD and heart doses (LAD Dmean, LAD Dmax, heart Dmean, and heart Dmax) were calculated and converted to 2-Gy equivalent doses (EQD2). Univariate and multivariable Cox regression analyses were performed to determine association with cardiac toxic effects. Potential dose thresholds for each of the 4 dose parameters were identified by receiver operating characteristic (ROC) curve analysis, after which Kaplan-Meier analysis was performed to compare cardiac event-free survival based on these constraints. RESULTS: Median follow-up time was 48 months. Thirty-six patients experienced a cardiac event, and 23 patients experienced a major cardiac event. On univariate and multivariable analyses, increased LAD Dmean, LAD Dmax, and heart Dmean were associated with increased risk of any cardiac event and a major cardiac event. ROC curve analysis identified a threshold LAD Dmean EQD2 of 2.8 Gy (area under the ROC curve, 0.69), above which the risk for any cardiac event was higher (P = .001). Similar results were seen when stratifying by LAD Dmax EQD2 of 6.7 Gy (P = .005) and heart Dmean EQD2 of 0.8 Gy (P = .01). CONCLUSIONS: Dose to the LAD correlated with adverse cardiac events in this cohort. Contouring and minimizing dose to the LAD should be considered for patients receiving radiation therapy for left-sided breast cancer.

Clinical Outcomes of Hypofractionated Whole Breast Irradiation in Early Stage, Biologically High-Risk Breast Cancer.

PURPOSE: Adoption of hypofractionated whole breast irradiation (HWBI) for patients with early-stage, biologically high-risk breast cancer remains relatively low. We compared clinical outcomes of conventionally fractionated whole breast irradiation (CWBI) versus moderate HWBI in this patient population. METHODS AND MATERIALS: We queried a prospectively maintained database for patients with early-stage (T1-2, N0, M0) breast cancer who received whole breast irradiation with either CWBI or moderate HWBI at a single institution. We included only patients with biologically high-risk tumors (defined as either estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, human epidermal growth factor receptor 2 amplified, and/or patients with a high-risk multigene assay) who received systemic chemotherapy. Inverse probability of treatment weighting was used to compare treatment cohorts and to estimate 5-year time to event endpoints. Hazard ratios (HR) and 95% confidence interval (CI) were determined based on Cox proportional hazards model. RESULTS: We identified 300 patients, of whom 171 received CWBI and 129 received HWBI. There was a statistically significant difference in median age at diagnosis, 59 years for CWBI versus 63 years for HWBI (P = .004), and in median follow-up time, 97 months for CWBI versus 55 months for HWBI (P < .001). After accounting for differences in patient and tumor characteristics with inverse probability of treatment weighting, we found similar 5-year freedom from local recurrence (HR, 0.76; 95% CI, 0.14-4.1), freedom from regional recurrence (HR, 3.395% CI 0.15-69), freedom from distant metastasis (HR 3.9, 95% CI 0.86-17), and disease-free survival (HR 0.84; 95% CI, 0.3-2.4), between those treated with CWBI and those treated with HWBI. Results were similar among each of the 3 high-risk subtypes. CONCLUSIONS: Our data support the use of moderate HWBI in patients with early-stage, biologically high-risk breast cancer.

Left anterior descending artery avoidance in patients receiving breast irradiation.

PURPOSE: Dose to the left anterior descending artery (LAD) may be significant in patients receiving left-sided irradiation for breast cancer. We investigated if prospective contouring and avoidance of the LAD during treatment planning were associated with lower LAD dose. METHODS AND MATERIALS: We reviewed dosimetric plans for 323 patients who received left whole breast or chest wall irradiation with or without internal mammary node (IMLN) coverage between 1/2014 and 1/2019 at a single institution. The LAD was contoured prospectively for 155 cases, and techniques were utilized to minimize LAD dose. Dose-volume-histograms from these patients were compared to those of 168 patients for whom the LAD was contoured retrospectively after treatment completion. EQD2 was calculated to account for fractionation differences. RESULTS: Compared to cases where the LAD was contoured retrospectively (n = 126), prospective LAD contouring (n = 124) was associated with lower unadjusted median max and mean LAD doses for 250 patients receiving whole-breast irradiation (WBI) without IMLN coverage: 8.5 Gy vs 5.2 Gy (p < 0.0001) and 3.6 Gy vs 2.7 Gy (p < 0.0001), respectively. EQD2 median max and mean LAD doses were also lower with prospective LAD contouring: 5.2 Gy vs 3.0 Gy (p < 0.0001) and 1.9 Gy vs 1.5 Gy (p < 0.0001), respectively. Compared to cases where the LAD was contoured retrospectively (n = 42), prospective LAD contouring (n = 31) was associated with lower max LAD doses for 73 patients with IMLN coverage: 20.4 Gy vs 14.3 Gy (p = 0.042). There was a nonsignificant reduction in median mean LAD dose: 6.2 Gy vs 6.1 Gy (p = 0.33). LAD doses were reduced while maintaining IMLN coverage (mean V90%Rx >90%). CONCLUSIONS: Prospective contouring and avoidance of the LAD were associated with lower max and mean LAD doses in patients receiving WBI and with lower max LAD doses in patients receiving IMLN treatment. Further reduction in LAD dose may require stricter optimization weighting or compromise in IMLN coverage.

A Protective Cap: Fundal Fluid Cap Facilitates a Reduction in Inner Ear Radiation Dose in the Radiosurgical Treatment of Vestibular Schwannoma.

OBJECTIVE: Assess inner ear radiation dose magnitude as it relates to fundal cap length and hearing outcomes in the radiosurgical treatment of vestibular schwannoma. STUDY DESIGN: Retrospective case series. SETTING: Tertiary neurotology referral center. PATIENTS: Patients treated with Gamma Knife radiosurgery for vestibular schwannoma between March 2007 and March 2017 were considered for this study. Exclusion criteria included pretreatment pure-tone average (PTA) >90 dB, neurofibromatosis type II, history of previous surgical resection, and follow-up less than 1 year. MAIN OUTCOME MEASURE: (s): Hearing function was assessed by maintenance of class A/B hearing level and maintenance of baseline hearing (≤20 dB change in PTA following Gamma Knife radiosurgery). RESULTS: Lower radiation doses delivered to the inner ear were associated with longer fundal cap lengths: mean cochlear dose (r = -0.130; p = 0.184), mean labyrinth dose (r = -0.406; p < 0.001), max cochlear dose (r = -0.326; p = 0.001), and max labyrinth dose (r = -0.360; p < 0.001). Kaplan-Meier analysis with log-rank testing revealed that patients with a mean labyrinth dose < 3 Gy achieved higher rates of preserving baseline hearing (≤20 dB change in PTA) following radiosurgery, compared to patients with a mean labyrinth dose ≥3 Gy (p < 0.001). A fundal fluid cap length of 2.5 mm was associated with the 3 Gy mean labyrinth dose threshold. CONCLUSIONS: We report that fundal cap presence facilitated the creation of treatment plans with a lower dose delivered to the labyrinth. By affording this dose reduction, a fundal cap may be associated with a slight improvement in hearing outcomes.

Pre-existing Vestibular Symptoms Are Associated With Acute Vestibular Symptoms After Gamma Knife Therapy for Vestibular Schwannoma.

OBJECTIVE: To identify pretreatment variables associated with the development of acute vestibular symptoms after Gamma Knife (GK) treatment for Vestibular Schwannoma (VS). STUDY DESIGN: Retrospective case series. SETTING: Tertiary neurotology referral center. PATIENTS: Patients treated with GK radiosurgery for VS between March 2007 and March 2017 were considered for this study. Patients with neurofibromatosis type II, previous VS surgery, follow-up less than 6 months, or the lack of T2 magnetic resonance imaging (MRI) sequences from the day of treatment were excluded. MAIN OUTCOME MEASURES: The presence of acute vestibular symptoms arising within 6 months after GK was the main outcome variable. Tumor, patient, and treatment characteristics were gathered from the medical record. RESULTS: In total, 98 patients met inclusion criteria. The incidence of acute vestibular symptoms occurring within 6 months after GK treatment was 46.9%. Post-GK vestibular symptoms were reported at a significantly higher frequency among subjects who had reported vestibular symptoms before their treatment (p = 0.001). Tumor size was not associated with a propensity to develop acute vestibular symptoms (p = 0.397). The likelihood of receiving a referral to vestibular rehabilitation services was not significantly different among patients with larger versus smaller tumor size, as defined by 1.6 cm and 1.4 cm thresholds (p = 0.896, p = 0.654). CONCLUSIONS: Inquiries aimed at revealing a history of vestibular complaints may prove useful in counseling patients on the likelihood of experiencing acute vestibular symptoms after treatment of Vestibular Schwannoma with Gamma Knife therapy.

Fundal Fluid Cap Is Associated With Hearing Preservation in the Radiosurgical Treatment of Vestibular Schwannoma.

OBJECTIVE: To evaluate the relationship between fundal fluid and hearing outcomes after treatment of vestibular schwannoma (VS) with Gamma Knife radiosurgery (GKRS). STUDY DESIGN: Retrospective case series. SETTING: Tertiary neurotology referral center. PATIENTS: Patients treated with GKRS for vestibular schwannoma between March 2007 and March 2017 were considered for this study. Exclusion criteria included pretreatment pure-tone average (PTA) >90 dB, neurofibromatosis type II, history of previous surgical resection, and follow-up less than 1 year. MAIN OUTCOME MEASURE(S): Hearing function was assessed both by preservation of serviceable hearing and by preservation of baseline hearing (≤20 dB change in PTA) after GKRS. Hearing preservation comparisons were made between groups of patients with and without a fundal fluid cap. RESULTS: Patients with a fundal cap had significantly higher rates of baseline hearing preservation (≤20 dB change in PTA) according to Kaplan-Meier survival analysis of all 106 patients (p = 0.006). By the 3rd year posttreatment, 70.9% of patients with a fundal cap had maintained a ≤20 dB change in PTA, while only 43.6% of patients without a fundal fluid cap achieved this outcome (p = 0.004). CONCLUSIONS: Fundal fluid present on pretreatment magnetic resonance imaging is predictive of improved baseline hearing preservation rates in patients undergoing GKRS for vestibular schwannoma when considering all patients with PTA ≤90 dB. Fundal fluid cap presence may serve as a favorable prognostic indicator to help set hearing expectations and guide patient selection efforts.

Pulsed radiation therapy for the treatment of newly diagnosed glioblastoma.

BACKGROUND: Pulsed radiation therapy (PRT) has shown effective tumor control and superior normal-tissue sparing ability compared with standard radiotherapy (SRT) in preclinical models and retrospective clinical series. This is the first prospective trial to investigate PRT in the treatment of patients with newly diagnosed glioblastoma (GBM). METHODS: This is a single-arm, prospective study. Patients with newly diagnosed GBM underwent surgery, followed by 60 Gy of PRT with concurrent temozolomide (TMZ). Each day, a 2-Gy fraction was divided into ten 0.2-Gy pulses, separated by 3-minute intervals. Patients received maintenance TMZ. Neurocognitive function (NCF) and quality of life (QoL) were monitored for 2 years using the Hopkins Verbal Learning Test‒Revised and the European Organisation for Research and Treatment of Cancer QLQ-C30 QoL questionnaire. Change in NCF was evaluated based on a minimal clinically important difference (MCID) threshold of 0.5 standard deviation. RESULTS: Twenty patients were enrolled with a median follow-up of 21 months. Median age was 60 years. Forty percent underwent subtotal resection, and 60% underwent gross total resection. One patient had an isocitrate dehydrogenase (IDH)-mutated tumor. Median progression-free survival (PFS) and overall survival (OS) were 10.7 and 20.9 months, respectively. In a post-hoc comparison, median OS for the prospective cohort was longer, compared with a matched cohort receiving SRT (20.9 vs 14 mo, P = 0.042). There was no decline in QoL, and changes in NCF scores did not meet the threshold of an MCID. CONCLUSIONS: Treatment of newly diagnosed GBM with PRT is feasible and produces promising effectiveness while maintaining neurocognitive function and QoL. Validation of our results in a larger prospective trial warrants consideration.