Bilirubin Elevation Caused by Naproxen Overdose: A Case Report Highlighting Laboratory Interference.

BACKGROUND Overdoses on over-the-counter (OTC) drugs are increasing in the United States, which includes widely available non-steroidal anti-inflammatory drugs (NSAIDs) like naproxen. Symptoms of NSAID toxicity are well known and nonspecific, including nausea, vomiting, abdominal pain, and headaches. Extreme cases can present with confusion, seizures, and renal failure. CASE REPORT We present the case of 63-year-old man with a history of hyperthyroidism and polysubstance use who had an elevated total bilirubin level after attempting suicide via ingestion of 16 tablets of naproxen. The patient presented with vague abdominal pain and nausea in the setting of 2 weeks of worsening psychiatric symptoms, including suicidal ideation. Vital signs, physical examination, and review of systems revealed no significant findings. Medical workup was notable only for an elevated total bilirubin level; workup for hemolysis, biliary stasis, hepatic dysfunction was all within normal limits. Direct bilirubin was not elevated. The patient received intravenous fluids and antiemetic medications, and indirect hyperbilirubinemia resolved by the following day. After ruling out other causes of hyperbilirubinemia, it was determined that his elevated bilirubin was due a naproxen metabolite, O-desmethylnaproxen (ODMN), that has been shown to interfere with certain bilirubin assays when naproxen is ingested over the therapeutic dose. CONCLUSIONS Supratherapeutic naproxen ingestion can lead to laboratory findings of elevated total bilirubin in some assays due to ODMN interference. With the rise in suicide attempts in the United States with OTCs, clinicians should consider laboratory error in such clinical circumstances where the clinical data does not fit the history and physical examination.

Race and Gender Shift among Academic Glaucoma Specialists in the Last 5 Decades.

Purpose: To evaluate the demographic composition of academic glaucoma specialists currently practicing in the United States. Design: Retrospective and observational study. Subjects: Academic glaucoma specialists identified from ophthalmology residency programs listed on the Doximity database. Methods: The American Board of Ophthalmology (ABO) membership directory, Doximity database, publicly available data, and direct communications were used to identify academic glaucoma specialists and their demographics. Information collected included-name, gender, race/ethnicity, geographic location, board certification date, academic affiliation, and academic rank. Ophthalmic age was defined as the number of years since ophthalmology board certification. Underrepresented minority (URM) groups were defined as Hispanics, Black or African Americans, Latinos, American Indians, or Alaskan Natives as defined by San Francisco match. In addition, the temporal, geographic, and academic rank distributions among females and URMs were explored. Main outcome measures: Women and URMs representations among academic glaucoma specialists across academic ranks, geographic regions, as well as ophthalmic age. Results: There were 457 active academic glaucoma specialists identified from 110 institutions in 38 states. Among them, 185 (40.5%) were women and 42 (9.2%) were URM. The proportion of women glaucoma specialists in academia had increased significantly with a rate of 1.049 in odds ratio (OR) per year (p < 0.001). However, there were no significant changes in the proportion of URMs over time. The earliest year of certification was 1,964 for males and 1,974 for females. When controlled for ophthalmic age, there were no significant differences in the distribution of women or URMs between the different academic ranks (p = 0.572 and p = 0.762, respectively). Among assistant professors, women had a significantly higher ophthalmic age compared to men (p < 0.001), but there was no significant difference in ophthalmic age in both the associate and full professor groups. There were no significant differences in the geographic distribution of gender (p = 0.516) and URM across United States regions (p = 0.238). Conclusion: The proportion of women among academic glaucoma specialists has significantly increased over the past 5 decades; however, the proportion of URMs has been stagnant in the same period. Enhancing URM representation among academic glaucoma specialists deserves to be a future priority. How to cite this article: Afzali K, Fujimoto DK, Mohammadi SO, et al. Race and Gender Shift among Academic Glaucoma Specialists in the Last 5 Decades. J Curr Glaucoma Pract 2023;17(2):98-103.

Patterns of Progression in Patients With Newly Diagnosed Glioblastoma Treated With 5-mm Margins in a Phase 1/2 Trial of 5-Fraction Stereotactic Radiosurgery With Concurrent and Adjuvant Temozolomide.

PURPOSE: In patients with newly diagnosed glioblastoma (GBM), tumor margins of at least 20 mm are the standard of care. We sought to determine the pattern of tumor progression in patients treated with 5-fraction stereotactic radiosurgery with 5-mm margins. METHODS AND MATERIALS: Thirty adult patients with newly diagnosed GBM were treated with 5-fraction stereotactic radiosurgery in escalated doses from 25 to 40 Gy with a 5-mm total treatment margin. Progression was scored as "in-field" if the recurrent tumor was within or contiguous with the 5-mm margin, "marginal" if between 5 and 20 mm, and "distant" if entirely occurring greater than 20 mm. As geometric patterns of progression do not reflect the biologic dose received, we calculated the minimum equi-effective dose in 2 Gy (EQD2) per day at the site of tumor recurrence. Progression was "dosimetrically in-field" if covered by a minimum EQD2 per day of 48 Gy10. RESULTS: From 2010 to 2016, 27 patients had progressed. Progression was in-field in 17 (63%), marginal in 3 (11%), and distant in 7 (26%) patients. In the 3 patients with marginal progression, the minimum EQD2 to recurrent tumor were 48 Gy10, 56 Gy10 (both considered dosimetrically in-field), and 7 Gy10 (ie, dosimetrically out-of-field). Median overall survival was 12.1 months for in-field (95% confidence interval [CI], 8.9-17.6), 15.1 months (95% CI, 10.1 to not achieved) for marginal, and 21.4 months (95% CI, 11.2-33.5) for distant progression. Patients with radiation necrosis were less likely to have in-field progression (1 of 7; 14%) compared with those without radiation necrosis (16 of 20; 80%; P = .003); those with necrosis had a median overall survival of 27.2 months (95% CI, 11.2-48.3) compared with 11.7 months (95% CI, 8.9-17.6) for patients with no necrosis (P = .077). CONCLUSIONS: In patients with newly diagnosed GBM treated with a 5-mm clinical target volume margin, 3 patients (11%) had marginal progression within 5 to 20 mm; only 1 patient (4%) may have dosimetrically benefitted from conventional 20-mm margins. Radiation necrosis was associated with in-field tumor control.

Controversies in Lung Cancer: Heterogeneity in Treatment Recommendations for Stage III NSCLC According to Disease Burden and Oncogenic Driver Alterations.

INTRODUCTION: Therapeutic options for stage III non-small-cell lung cancer (NSCLC) consist of definitive chemoradiation, surgery combined with neoadjuvant/adjuvant chemotherapy, and trimodality therapy. More recently, biologically driven systemic therapy options, including immunotherapy and targeted therapy, have become increasingly available. METHODS: A customized, case-based survey was designed and distributed to members of the International Association for the Study of Lung Cancer (IASLC) to determine practice habits and preferences for NSCLC patients with stage III disease and N2 to N3 nodal involvement. RESULTS: Data were compiled from 87 respondents from 31 countries, including medical oncologists (49%), surgical oncologists (24%), and radiation oncologists (21%). Definitive chemoradiation was more likely to be recommended for stage IIIC (98.2%) or stage IIIB (75.8%) scenarios compared with stage IIIA (59.6%) without actionable driver alterations (P < .0001 and .0003, respectively); and chemoradiation was more likely for stage IIIB (57.7%) compared to stage IIIA (39.9%) with actionable EGFR/ALK alterations (P = .008). Surgery was more likely to be recommended in the presence of an actionable alteration (38.7% vs. 19%, P < .0001). Surgeons were more likely than medical oncologists to recommend surgical approaches in scenarios without actionable alterations (25.6% vs. 11.2%, P < .0001) or with actionable alterations (57.5% vs. 31.1%, P = .0001). DISCUSSION: The dominant recommended strategy for stage III NSCLC was chemoradiation, although respondents were more likely to recommend surgical approaches in the presence of actionable alterations. Despite the lack of reported clinical trial data, many IASLC lung cancer experts favored targeted therapy when actionable driver alterations were present.

Phase I/II Dose-Escalation Trial of 3-Fraction Stereotactic Radiosurgery for Resection Cavities From Large Brain Metastases: Health-related Quality of Life Outcomes.

OBJECTIVES: We investigated differences in quality of life (QoL) in patients enrolled on a phase I/II dose-escalation study of 3-fraction resection cavity stereotactic radiosurgery (SRS) for large brain metastases. METHODS: Eligible patients had 1 to 4 brain metastases, one of which was a resection cavity 4.2 to 33.5 cm3. European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaires core-30 (QLQ-30) and brain cancer specific module (QLQ-BN20) were obtained before SRS and at each follow-up. Nine scales were analyzed (global health status; physical, social, and emotional functioning; motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty). QoL was assessed with mixed effects models. Differences ≥10 points with q-value (adjusted P-value to account for multiplicity of testing) <0.10 were considered significant. RESULTS: Between 2009 and 2014, 50 enrolled patients completed 277 QoL questionnaires. Median questionnaire follow-up was 11.8 months. After SRS, insomnia demonstrated significant improvement (q=0.032, -17.7 points at 15 mo post-SRS), and future uncertainty demonstrated significant worsening (q=0.018, +9.9 points at 15 mo post-SRS). Following intracranial progression and salvage SRS, there were no significant QoL changes. The impact of salvage whole brain radiotherapy could not be assessed because of limited data (n=4 patients). In the 28% of patients that had adverse radiation effect, QoL had significant worsening in 3 metrics (physical functioning, q=0.024, emotional functioning q=0.001, and future uncertainty, q=0.004). CONCLUSIONS: For patients treated with 3-fraction SRS for large brain metastasis cavities, 8 of 9 QoL metrics were unchanged or improved after initial SRS. Intracranial tumor progression and salvage SRS did not impact QoL. Adverse radiation effect may be associated with at least short-term QoL impairments, but requires further investigation.

Outcomes of Artificial Intelligence Volumetric Assessment of Kidneys and Renal Tumors for Preoperative Assessment of Nephron-Sparing Interventions.

Background: Renal-cell carcinoma is the most common kidney cancer and the 13th most common cause of cancer death worldwide. Partial nephrectomy and percutaneous ablation, increasingly utilized to treat small renal masses and preserve renal parenchyma, require precise preoperative imaging interpretation. We sought to develop and evaluate a convolutional neural network (CNN), a type of deep learning (DL) artificial intelligence (AI), to act as a surgical planning aid by determining renal tumor and kidney volumes through segmentation on single-phase CT. Materials and Methods: After Institutional Review Board approval, the CT images of 319 patients were retrospectively analyzed. Two distinct CNNs were developed for (1) bounding cube localization of the right and left hemiabdomen and (2) segmentation of the renal parenchyma and tumor within each bounding cube. Training was performed on a randomly selected cohort of 269 patients. CNN performance was evaluated on a separate cohort of 50 patients using Sorensen-Dice coefficients (which measures the spatial overlap between the manually segmented and neural network-derived segmentations) and Pearson correlation coefficients. Experiments were run on a graphics processing unit-optimized workstation with a single NVIDIA GeForce GTX Titan X (12GB, Maxwell Architecture). Results: Median Dice coefficients for kidney and tumor segmentation were 0.970 and 0.816, respectively; Pearson correlation coefficients between CNN-generated and human-annotated estimates for kidney and tumor volume were 0.998 and 0.993 (p < 0.001), respectively. End-to-end trained CNNs were able to perform renal parenchyma and tumor segmentation on a new test case in an average of 5.6 seconds. Conclusions: Initial experience with automated DL AI demonstrates that it is capable of rapidly and accurately segmenting kidneys and renal tumors on single-phase contrast-enhanced CT scans and calculating tumor and renal volumes.

Prospective randomized trial of email and/or telephone reminders to enhance vaginal dilator compliance in patients undergoing brachytherapy for gynecologic malignancies.

PURPOSE: To evaluate whether email survey +/- telephone reminder versus no intervention would facilitate compliance with vaginal dilator use in women undergoing brachytherapy for gynecologic malignancies and to assess changes in vaginal canal (VC) length between the groups. METHODS AND MATERIALS: A 72 patients were enrolled onto a three-arm single-institution randomized prospective clinical trial and stratified by whether they received external beam radiation treatment in addition to brachytherapy and by total radiation dose to the VC. Patients were subsequently randomized to one of three groups: email survey alone, email survey + telephone reminder, or no intervention. Change in VC length over time was measured for each patient. RESULTS: The median follow-up time was 17.3 months. There were no differences in patient-reported compliance between the 3 groups. Vaginal dilator compliance fell over the course of the study period and was 33% at 24 months. Baseline VC length and radiation dose were found to be the most important predictors of VC shortening over time. When accounting for baseline length, radiation dose, and follow-up time, type of intervention did not impact changes in VC length from baseline (p = 0.20). CONCLUSIONS: Our study is the first to show the importance of baseline VC length as it relates to VC shortening following brachytherapy for gynecologic cancers and highlights the difficulties in improving VC compliance among this patient population. Further study is required to improve the incidence of late effects in this group.

Phase II trial evaluating efficacy of a Fitbit program for improving the health of endometrial cancer survivors.

BACKGROUND: Despite the favorable prognosis of early stage endometrial cancer, mortality from cardiovascular disease is high. We aimed to evaluate the efficacy of a Fitbit program to improve physical activity in endometrial cancer survivors. METHODS: Eligible patients were diagnosed with stage IA-IIIA endometrial adenocarcinoma, ≥3 months out from treatment. Participants received a Fitbit Alta and were randomized to receive communication via telephone or electronic methods (email/text). Communication was every two weeks for two months, then once during months four and five. Average daily steps were assessed weekly for nine months. RESULTS: The 46 analyzable patients demonstrated a baseline of 5641 median daily average steps. Average steps increased by 22% at 6 months but decreased to baseline by nine months. Baseline activity level (daily steps and walks per week) was the greatest predictor of activity level. Only the telephone intervention participants demonstrated increased activity level at several timepoints, although not maintained by nine months. BMI was unchanged. There was mild improvement in physical and social well-being in those with low baseline well-being (p = 0.009 and 0.014, respectively), regardless of intervention group. Emotional well-being correlated with step count (p = 0.005). CONCLUSIONS: Activity level was low and mildly improved on the Fitbit program with the telephone intervention, but effects did not persist by study completion. The program had the greatest impact on a select group of telephone intervention patients with high baseline walking frequency and low baseline step count. Others may require more intense intervention to promote more robust/persistent lifestyle changes.

Recurrence risk factors in stage IA grade 1 endometrial cancer.

OBJECTIVES: Patients with early-stage endometrial cancers (EC) with disease recurrences have worse survival outcomes. The purpose of this study was to identify clinical and pathologic factors that predict for all recurrences in stage IA grade 1 (IAG1) EC. METHODS: Records from patients diagnosed with EC were retrospectively reviewed. Baseline characteristics of 222 patients with IAG1 EC who underwent surgical resection were analyzed. Cox proportional hazard analysis was used to identify univariate and multivariate risk factors that predict for recurrence. RESULTS: Seventeen (7.65%) patients had recurrences. The 3-year cumulative incidence of recurrence were significantly higher for patients with time from biopsy to surgery ≥6 months (54% vs. 8%, p=0.003), simple hysterectomy with ovarian preservation vs. total hysterectomy and bilateral salpingo-oophorectomy (31% vs. 9%, p=0.032), any myometrial invasion vs. no invasion (18% vs. 2%, p=0.004), and tumor size ≥2 cm (15% vs. 2%, p=0.021). On, multivariate analysis, any myometrial invasion, increasing time from biopsy to surgery, and larger tumor size were independent predictors of any recurrence. Patients with recurrences had worse outcomes than those without (5-year overall survival [OS]=60%; 95% confidence interval [CI]=16%-86% vs. 5-year OS=95%; 95% CI=87%-99%, respectively, p=0.003). CONCLUSION: Time from biopsy to surgery, larger tumors, and myometrial invasion are the most important predictors of recurrence. Though the recurrence rates are generally low in IAG1 EC, the survival rate for the patients with recurrences was worse than those without. Identification of additional recurrence risk factors can help select patients who may benefit from adjuvant treatment.

A phase I/II trial of 5-fraction stereotactic radiosurgery with 5-mm margins with concurrent temozolomide in newly diagnosed glioblastoma: primary outcomes.

BACKGROUND: We sought to determine the maximum tolerated dose (MTD) of 5-fraction stereotactic radiosurgery (SRS) with 5-mm margins delivered with concurrent temozolomide in newly diagnosed glioblastoma (GBM). METHODS: We enrolled adult patients with newly diagnosed glioblastoma to 5 days of SRS in a 3 + 3 design on 4 escalating dose levels: 25, 30, 35, and 40 Gy. Dose limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events grades 3-5 acute or late CNS toxicity, including adverse radiation effect (ARE), the imaging correlate of radiation necrosis. RESULTS: From 2010 to 2015, thirty patients were enrolled. The median age was 66 years (range, 51-86 y). The median target volume was 60 cm3 (range, 14.7-137.3 cm3). DLT occurred in 2 patients: one for posttreatment cerebral edema and progressive disease at 3 weeks (grade 4, dose 40 Gy); another patient died 1.5 weeks following SRS from postoperative complications (grade 5, dose 40 Gy). Late grades 1-2 ARE occurred in 8 patients at a median of 7.6 months (range 3.2-12.6 mo). No grades 3-5 ARE occurred. With a median follow-up of 13.8 months (range 1.7-64.4 mo), the median survival times were: progression-free survival, 8.2 months (95% CI: 4.6-10.5); overall survival, 14.8 months (95% CI: 10.9-19.9); O6-methylguanine-DNA methyltransferase hypermethylated, 19.9 months (95% CI: 10.5-33.5) versus 11.3 months (95% CI: 8.9-17.6) for no/unknown hypermethylation (P = 0.03), and 27.2 months (95% CI: 11.2-48.3) if late ARE occurred versus 11.7 months (95% CI: 8.9-17.6) for no ARE (P = 0.08). CONCLUSIONS: The per-protocol MTD of 5-fraction SRS with 5-mm margins with concurrent temozolomide was 40 Gy in 5 fractions. ARE was limited to grades 1-2 and did not statistically impact survival.

Improving gynecologic brachytherapy patient experience by optimizing MRI, anesthesia, and scheduling to decrease the length of time tandem and ovoid applicators are in place.

PURPOSE: Brachytherapy requires multiple different steps and plays a critical role in treatment for gynecological cancer. In an effort to improve gynecologic patient experience, we investigated how different aspects of the procedure influence how long the patient has the brachytherapy applicator in place. METHODS AND MATERIALS: We prospectively recorded 145 consecutive tandem and ovoid treatments for 33 patients and determined how anesthesia vs. conscious sedation, MRI or not, and the number of procedures in the day impact applicator in time. The data were analyzed in a mixed effects linear regression model to account for the within-patient correlation. RESULTS: We found average applicator in place time was 179 minutes (range: 87-311 minutes). Patients who received anesthesia had a significant increase in length of applicator in patient time by an average of 42 minutes compared with those who received conscious sedation. Undergoing an MRI increased length of applicator in time by an average of 66 minutes, although the actual MRI performed generally took less than 30 minutes. Having three or more procedures scheduled for 1 day increased the length of time the tandem and ovoid was inserted by an average of 35 minutes. CONCLUSION: The use of anesthesia vs. conscious sedation, MRI scans for treatment planning, and number of procedures scheduled per day have significant influence on the duration of brachytherapy treatments. This information can help us work to optimize scheduling and thereby improve patient brachytherapy experience.

Long-Term Update of Stereotactic Radiosurgery for Benign Spinal Tumors.

BACKGROUND: Stereotactic radiosurgery (SRS) for benign intracranial tumors is an established standard of care. The widespread implementation of SRS for benign spinal tumors has been limited by lack of long-term data. OBJECTIVE: To update our institutional experience of safety and efficacy outcomes after SRS for benign spinal tumors. METHODS: We performed a retrospective cohort study of 120 patients with 149 benign spinal tumors (39 meningiomas, 26 neurofibromas, and 84 schwannomas) treated with SRS between 1999 and 2016, with follow-up magnetic resonance imaging available for review. The primary endpoint was the cumulative incidence of local failure (LF), with death as a competing risk. Secondary endpoints included tumor shrinkage, symptom response, toxicity, and secondary malignancy. RESULTS: Median follow-up was 49 mo (interquartile range: 25-103 mo, range: 3-216 mo), including 61 courses with >5 yr and 24 courses with >10 yr of follow-up. We observed 9 LF for a cumulative incidence of LF of 2%, 5%, and 12% at 3, 5, and 10 yr, respectively. Excluding 10 tumors that were previously irradiated or that arose within a previously irradiated field, the 3-, 5-, and 10-yr cumulative incidence rates of LF were 1%, 2%, and 8%, respectively. At last follow-up, 35% of all lesions had decreased in size. With a total of 776 patient-years of follow-up, no SRS-related secondary malignancies were observed. CONCLUSION: Comparable to SRS for benign intracranial tumors, SRS provides longer term local control of benign spinal tumors and is a standard-of-care alternative to surgical resection.

Improving brachytherapy efficiency with dedicated dosimetrist planners.

PURPOSE: To investigate the different factors affecting the procedure duration for high-dose-rate brachytherapy for gynecologic malignancies. METHODS AND MATERIALS: We prospectively recorded 86 consecutive vaginal cylinder (VC) treatments and 82 tandem and ovoid treatments. Key time points in the brachytherapy process, identity of the planner and checker, number of treatments per day, and fraction number per patient were recorded. The data were analyzed in a mixed effects linear regression model to account for the within patient correlation. Post hoc pair-wise comparisons were performed using a Dunnett's adjustment for comparisons to a single control group and using a Tukey adjustment for all pair-wise comparisons. RESULTS: We focused on several key time intervals in the treatment: total, nursing/anesthesia preprocedure, procedure, contouring, and planning times. In analysis, multiple factors significantly influenced VC timing but not tandem and ovoid timing. The planners were separated and analyzed based on experience and profession. Inexperienced physicists planning times were on average 18 min (p = 0.0010) and 14 min (p = 0.0038) slower than dedicated brachytherapy dosimetrist and experienced physicists, respectively. An increase in the number of procedures for the day of treatment increased the VC total time (p = 0.0218). The VC procedure time changed depending on whether it was the patients' first, second, or third VC treatment (p < 0.0001). CONCLUSIONS: The use of dosimetrists as dedicated planners for brachytherapy is more cost and time efficient. There are multiple variables affecting brachytherapy treatment with actionable opportunities to improve procedure scheduling.

Newly diagnosed glioblastoma: adverse socioeconomic factors correlate with delay in radiotherapy initiation and worse overall survival.

The optimal time for starting radiation in patients with glioblastoma (GBM) is controversial. We aimed to evaluate postoperative radiotherapy treatment patterns and the impact of timing of radiotherapy on survival outcomes in patients with GBM using a large, national hospital-based registry in the era of Stupp chemoradiation. We performed a retrospective cohort study using the National Cancer Data Base and identified adults with GBM diagnosed between 2010 and 2013 and treated with chemoradiation. We classified time from surgery/biopsy to radiation start into the following categories: <15 days, 15-21 days, 22-28 days, 29-35 days, 36-42 days and >42 days. We assessed the relation between time to radiation start and survival using Cox proportional hazards modeling adjusting for clinically relevant variables that were selected a priori. We used multivariate logistic modeling to determine factors independently associated with receipt of delayed radiation treatment. A total of 12 738 patients met our inclusion criteria after our cohort selection process. The majority of patients underwent either gross total (n = 5270, 41%) or subtotal (n = 4700, 37%) resection, while 2768 patients (22%) underwent biopsy only. Median time from definitive surgery or biopsy to initiation of radiation was 29 days (interquartile range 24-36 days). For patients who had biopsy or subtotal resection, earlier initiation of radiation did not appear to be associated with improved survival. However, among patients who underwent gross total resection, there appeared to be improved survival with early initiation of radiation. Patients who initiated radiation within 15-21 days of gross total resection had improved survival (hazard ratio 0.82, 95% confidence interval 0.69-0.98, P = 0.03) compared with patients who had delayed (>42 days after surgery) radiation. There was also a trend (P = 0.07 to 0.12) for improved survival for patients who initiated radiation within 22-35 days of gross total resection compared with patients who had delayed radiation. Patients who were black, had Medicaid or other government insurance or were not insured, and who lived in metropolitan areas or further away from the treating facility had higher odds of receiving radiation >35 days after gross total resection. Patients who lived in higher income areas had higher odds of receiving radiation within 35 days of a gross total resection. In a large cohort of patients with GBM treated with chemoradiation, our data suggest a survival benefit in initiating radiotherapy within 35 days after gross total resection. Further research is warranted to understand barriers to timely access to optimal therapy.

Imaging changes over 18 months following stereotactic radiosurgery for brain metastases: both late radiation necrosis and tumor progression can occur.

Following stereotactic radiosurgery (SRS) for brain metastases, the median time range to develop adverse radiation effect (ARE) or radiation necrosis is 7-11 months. Similarly, the risk of local tumor recurrence following SRS is < 5% after 18 months. With improvements in systemic therapy, patients are living longer and are at risk for both late (defined as > 18 months after SRS) tumor recurrence and late ARE, which have not previously been well described. An IRB-approved, retrospective review identified patients treated with SRS who developed new MRI contrast enhancement > 18 months following SRS. ARE was defined as stabilization/shrinkage of the lesion over time or pathologic confirmation of necrosis, without tumor. Local failure (LF) was defined as continued enlargement of the lesion over time or pathologic confirmation of tumor. We identified 16 patients, with a median follow-up of 48.2 months and median overall survival of 73.0 months, who had 19 metastases with late imaging changes occurring a median of 32.9 months (range 18.5-63.2 months) after SRS. Following SRS, 12 lesions had late ARE at a median of 33.2 months and 7 lesions had late LF occurring a median of 23.6 months. As patients with cancer live longer and as SRS is increasingly utilized for treatment of brain metastases, the incidence of these previously rare imaging changes is likely to increase. Clinicians should be aware of these late events, with ARE occurring up to 5.3 years and local failure up to 3.8 years following SRS in our cohort.

Phase 1/2 Trial of 5-Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma: Health-Related Quality of Life Results.

PURPOSE: We report a longitudinal assessment of health-related quality of life (HRQOL) in patients with glioblastoma (GBM) treated on a prospective dose escalation trial of 5-fraction stereotactic radiosurgery (25-40 Gy in 5 fractions) with concurrent and adjuvant temozolomide. METHODS: HRQOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire core-30 (QLQ-C30) general, the EORTC quality of life questionnaire-brain cancer specific module (QLQ-BN20), and the M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Questionnaires were completed at baseline and at every follow-up visit after completion of radiosurgery. Changes from baseline for 9 predefined HRQOL measures (global quality of life, physical functioning, social functioning, emotional functioning, motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty) were calculated at every time point. RESULTS: With a median follow-up time of 10.4 months (range, 0.4-52 months), 139 total HRQOL questionnaires were completed by the 30 patients on trial. Compliance with HRQOL assessment was 76% at 12 months. Communication deficit significantly worsened over time, with a decline of 1.7 points per month (P=.008). No significant changes over time were detected in the other 8 scales of our primary analysis, including global quality of life. Although 8 patients (27%) experienced adverse radiation effects (ARE) on this dose escalation trial, it was not associated with a statistically significant decline in any of the primary HRQOL scales. Disease progression was associated with communication deficit, with patients experiencing an average worsening of 13.9 points per month after progression compared with 0.7 points per month before progression (P=.01). CONCLUSION: On this 5-fraction dose escalation protocol for newly diagnosed GBM, overall HRQOL remained stable and appears similar to historical controls of 30 fractions of radiation therapy. Tumor recurrence was associated with worsening communication deficit, and ARE did not correlate with a decline in HRQOL.