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XLSX file 10K, Homologous mutations from S. pombe tor2 in H. sapiens MTOR are listed

PDF file 73K, mTOR R1208C, V2006L, R2152C, and R2430M fail to confer increased S6K1 phosphorylation

PDF file 106K, S2215Y mTOR activates mTORC1 signaling similar to WT and mutant PI3K-p110alpha

PDF file 85K, mTOR pathway mutations

XLSX file 89K, All mutations from the cBIO and COSMIC databases in mTOR pathway genes, excluding MTOR, are listed

PDF file 82K, Supplementary Figure and Table Legends

PDF file 143K, mTOR mutants alter Deptor binding and nutrient deprivation, but not sensitivity to mTOR inhibitors

PDF file 94K,Non-recurrent MTOR mutations confer different degrees of mTORC1 activation

PDF file 154K, Recurrent mTOR mutations mapped onto the crystal structure of mTOR

XLSX file 17K, All site-directed mutagenesis primers to generate mutant mTOR and Rheb1 are listed

To evaluate the utilization of brachytherapy and duration of treatment on overall survival for locally advanced cervical cancer.The National Cancer Database (NCDB) was queried to identify stage II-IVA cervical cancer patients diagnosed in the United States between 2004 and 2015 who were treated with definitive chemoradiation therapy. We defined standard of care (SOC) treatment as receiving external beam radiation therapy (EBRT) and concurrent chemotherapy, brachytherapy (BT), and completing treatment within 8 weeks, and compared SOC treatment to non-SOC. The primary outcome was overall survival (OS). We also evaluated the effect of sociodemographic and clinical variables on receiving SOC.We identified 10,172 women with locally advanced cervical cancer primarily treated with chemotherapy and concurrent EBRT of which 6047 (59.4%) patients received brachytherapy, and only 2978 (29.3%) completed treatment within 8 weeks (SOC). Receipt of SOC was associated with significantly improved overall survival (median OS 131.0 mos vs 95.5 mos, 78.1 mos, 49.2 mos; p 0.0001). Furthemore, in patients whose treatment extended beyond 8 weeks, brachytherapy was still associated with an improved survival (median OS 95.5 vs 49.2 mos, p 0.0001). More advanced stage, Non-Hispanic Black race, lower income, lack of insurance or government insurance, less education, and rural residence were associated with decreased likelihood of receiving SOC.Completing standard of care concurrent chemoradiation therapy and brachytherapy in the recommended 8 weeks was associated with a superior overall survival. Patients who received brachytherapy boost show superior survival to patients receiving EBRT alone, regardless of treatment duration. Disparities in care for vulnerable populations highlight the challenges and importance of care coordination for patients with cervical cancer.

Introduction Management of central nervous system (CNS) metastases in patients with driver-mutated NSCLC has traditionally incorporated both tyrosine kinase inhibitors (TKIs) and intracranial radiation. Whether next generation, CNS-penetrant TKIs can be used alone without upfront radiation, however, remains unknown. This multi-institutional retrospective analysis aimed to compare outcomes in patients with EGFR- or ALK-positive NSCLC who received CNS-penetrant TKI therapy alone versus in combination with radiation for new or progressing intracranial metastases. Methods Data were retrospectively collected from three academic institutions. Two treatment groups (CNS-penetrant TKI alone versus TKI + CNS radiation therapy) were compared for both EGFR- and ALK-positive cohorts. Outcome variables included time to progression, time to intracranial progression, and time to treatment failure, measured from the date of initiation of CNS-penetrant TKI therapy. Results A total of 147 patients were included (EGFR n = 94, ALK n = 52, both n = 1). In patients receiving radiation, larger metastases, neurologic symptoms, and receipt of steroids were more common. There were no significant differences between TKI and CNS radiation therapy plus TKI groups for any of the study outcomes, including time to progression (8.5 versus 6.9 mo, p = 0.13 [EFGR] and 11.4 versus 13.4 mo, p = 0.98 [ALK]), time to intracranial progression (14.8 versus 20.5 mo, p = 0.51 [EGFR] and 18.1 versus 21.8 mo, p = 0.65 [ALK]), or time to treatment failure (13.8 versus 8.6 mo, p = 0.26 [EGFR] and 13.5 versus 23.2 mo, p = 0.95 [ALK]). Conclusions These results provide preliminary evidence that intracranial activity of CNS-penetrant TKIs may enable local radiation to be deferred in appropriately selected patients without negatively affecting progression.

Background: Minority and low-income patients disproportionately experience dermatologic access challenges. Store-and-forward (SAF) teledermatology has emerged as a model of care delivery that may i...

We sought to evaluate whether the survival benefit of adjuvant radiotherapy in patients with node-positive vulvar cancer is maintained in older patients, who comprise a large subgroup of patients with vulvar cancer.The National Cancer Database (NCDB) was queried for patients aged 65 years or older, who were diagnosed with vulvar squamous cell carcinoma from 2004 to 2017 and underwent surgery with confirmed node-positive disease. Statistical analysis was performed with propensity-score matching, chi-square test, log-rank test, Kaplan-Meier, and multivariable Cox proportional regression.A total of 2396 patients were analyzed, and 1517 (63.3%) received adjuvant radiotherapy. Median follow-up was 73 months. Median age at diagnosis was 77 years (range 65-90). In the propensity score-matched cohort, five-year overall survival (OS) was 29%. Five-year OS was 33% in patients who received surgery followed by adjuvant radiotherapy and 26% in patients who received surgery alone (p0.0001). Multivariable analysis continued to demonstrate a survival benefit associated with the addition of adjuvant radiotherapy (OR 0.77 [95% CI 0.69-00.87], p0.001). Adjuvant radiotherapy was associated with improved OS among patients aged 65-84 (5-year OS 35% vs 29%, p = 0.0004), but not in patients aged 85 years and older (5-year OS 20% vs 19%, p = 0.32).This NCDB study suggests that in older patients with node-positive vulvar cancer, radiotherapy continues to be a vital component of multimodality therapy. However, a comprehensive and geriatrics-specific approach is crucial for treating older adults with node-positive vulvar cancer, as the benefit of adjuvant radiotherapy may be compromised by treatment-related morbidity/toxicity.

INTRODUCTION: This study sought to compare the clinicopathologic features of women with breast cancer presenting in South Africa, Botswana, and the United States (US). METHODS: Breast cancer samples from Botswana (n = 384, 2011–2015), South Africa (n = 475, 2016–2017), and the US (n = 361,353, 2011–2012) were retrospectively reviewed. RESULTS: The median age of sub-Saharan African women presenting with breast cancer (age 54 in Botswana and South Africa) was younger than that of those in the US (age 61) (P < 0.001). Sub-Saharan women were more likely to present with advanced stage disease than US counterparts (64.7% in Botswana, 63.3% in South Africa, 13% in the US, P < 0.001). Triple negative disease was highest in Botswana (21.3%) compared to South Africa (11.4%) and the US (12.94%) (P < 0.001). Differences in receptor status at presentation among the three cohorts (P < 0.001) were not observed when the cohorts were stratified by ethnicity. Black/multiracial patients in Botswana and the US were the most likely subsets to present with the adverse characteristic of triple negative disease (21.3% and 23.2%, respectively). No correlation was found between HIV and receptor status in the Botswana (P = 0.513) or South African (P = 0.352) cohorts. CONCLUSIONS: Here we report receptor status patterns at presentation in Botswana and South Africa. This study reveals important similarities and differences which may inform policy and provide context for future epidemiologic trends of breast cancer in low- and-middle-income countries particularly in sub-Saharan Africa.

This cohort study examines disparities in patient portal use among oncology patients.

Purpose/objective(s) Sarcoma is a rare, diverse oncologic diagnosis with a complex spectrum of presentation. Advances in multimodality therapy including treatment with radiotherapy have shifted the paradigm from amputation to limb-sparing surgery (LSS) or limited resections. Management of recurrent sarcoma after LSS is challenging and may require subsequent amputation. Here, we sought to identify factors associated with amputation or radical excision as salvage therapy for recurrent sarcoma. Materials/methods Sarcomas treated at a single institution were identified. Patients who required any salvage surgery for recurrent sarcoma were selected. Comparison was made between patients receiving LSS or limited re-excision versus amputation or radical, whole organ excision at the time of first salvage surgery. Demographic, tumor, and treatment characteristics were retrospectively reviewed. Univariate comparison was made using Chi squared test and analysis of variance. Multivariate logistic regression was completed to assess factors associated with salvage surgery type. Results A total 5,774 sarcoma patients were evaluated between 2000 and 2018. Salvage surgery for recurrent sarcoma was required for 519 patients (9%). Patients requiring upfront radical surgery (n = 17) were excluded. The study included 502 patients with 375 (75%) receiving salvage limb sparing surgery and 127 (25%) receiving salvage amputation or radical surgery at the time of their second surgery. Soft tissue sarcoma (STS, n = 455, 91%) was more common than osseous sarcoma (n = 47, 9%), including 173 (34%) STS of extremities. Univariate analysis revealed that age, gender, and race were not associated with amputation or radical surgery; however, higher stage, higher grade, and no radiation in primary treatment were associated with subsequent amputation (P Conclusion In a single institution cohort, need for amputation or radical excision at the time of salvage surgery after LSS for recurrent disease was rare, in keeping with modern sarcoma experiences. Retrospective review suggests that higher stage is associated with radical salvage options while receipt of radiation during primary treatment is inversely related. Further inquiry into the clinical characteristics and the patterns of failure may clarify the relationship between stage, radiation and radical salvage therapy. Future work may aid in avoiding morbid salvage therapy.

Although multimodality therapy has been shown to improve outcomes for patients with high-risk endometrial carcinoma, optimal type and timing of adjuvant therapies is unknown.Patients with stage I-IVA endometrial carcinoma diagnosed from 2004 to 2015, and treated with surgery, chemotherapy, and radiation were identified in the National Cancer Database. Adjuvant treatment was categorized as sequential radiation followed by chemotherapy (RT-CT), concurrent chemoradiation (CCRT, RT and CT started within 7 days), or sequential chemotherapy followed by radiation (CT-RT). Analysis for propensity score matched (PSM) cohorts comparing RT-CT to CCRT and CT-RT groups was additionally performed.A total of 17,070 patients were identified, including 12,402 (72.7%) treated with RT-CT, 2,153 (12.6%) with CCRT, and 2,515 (14.7%) with CT-RT. Median follow-up was 44.3 months. Five-year overall-survival (OS) by adjuvant treatment regimen was 77.3% (95% CI 76.4%-78.2%), 74.3% (95% CI 72.0%-76.3%), and 74.4% (95% CI 72.5%-76.3%), respectively (p .001). When unmatched cohorts were stratified by stage, adjuvant RT-CT was associated with improved OS in stage I and III patients. A similar survival advantage associated with RT-CT was observed in PSM cohorts comparing RT-CT group to CCRT/CT-RT group (5-year OS 77.4% vs 74.2%, p = .001). However, the difference in OS was significant only among stage III patients (RT-CT 73.9% compared to CCRT/CT-RT 69.7%, p =.002).Our findings suggest survival benefit with adjuvant RT-CT compared to CT-RT or CCRT in patients undergoing trimodality therapy for endometrial cancer. This survival benefit may be limited to stage III patients.

OBJECTIVE Blood product utilization is monitored to prevent unnecessary transfusions. Head-and-neck pedicled flap reconstruction transfusion-related outcomes were assessed. METHODS One hundred and thirty-six pedicled flap patients were reviewed: 64 supraclavicular artery island flaps (SCAIF), 57 pectoralis major (PM) flaps, and 15 submental (SM) flaps. Outcome parameters included flap-related complications, medical complications, length of stay (LOS), and flap survival. Multivariable logistic regression analyses were performed. Multivariable logistic regression analyses were performed to adjust for relevant pre- and perioperative factors. RESULTS Of all head-and-neck pedicled flap patients included in our analyses (n = 136), 40 (29.4%) received blood transfusions. The average pretransfusion hematocrit (Hct) was 24.3% ± 0.5%, with 2.65 ± 0.33 units transfused and a posttransfusion Hct increase of 5.0% ± 0.6%. Transfusion rates differed with PM (47.4%), SCAIF (17.2%), and SM (13.3%) flaps (P

Optogenetics is a transformative technology based on light-sensitive microbial proteins, known as opsins, that enable precise modulation of neuronal activity with pulsed radiant energy. Optogenetics has been proposed as a means to improve auditory implant outcomes by reducing channel interaction and increasing electrode density, but the introduction of opsins into cochlear spiral ganglion neurons (SGNs) in vivo has been challenging. Here we test opsin delivery using a synthetically developed ancestral adeno-associated virus (AAV) vector called Anc80L65. Wild-type C57BL/6 mouse pups were injected via the round window of cochlea with Anc80L65 carrying opsin Chronos under the control of a CAG promoter. Following an incubation of 6-22 weeks, pulsed blue light was delivered to cochlear SGNs via a cochleosotomy approach and flexible optical fiber. Optically evoked auditory brainstem responses (oABRs) and multiunit activity in inferior colliculus (IC) were observed. Post-experiment cochlear histology demonstrated opsin expression in SGNs (mean = 74%), with an even distribution of opsin along the cochlear basal/apical gradient. This study is the first to describe robust SGN transduction, opsin expression, and optically evoked auditory electrophysiology in neonatal mice. Ultimately, this work may provide the basis for a new generation of cochlear implant based on light.

Purpose Medical assistants (MAs) occupy an increasingly prevalent role in the clinical setting. Subspecialized fields such as oncology require specific clinical knowledge; however, MAs have few requirements for continued education. Here we assess the role and effect of a pilot MA Radiation Oncology education curriculum. Methods and Materials A needs assessment survey was conducted and reviewed to develop a comprehensive introductory oncology curriculum. A resident physician-led program was implemented in an academic cancer care center consisting of monthly, 1-hour lectures. Pre- and postlecture surveys were administered to assess learning. Quarterly surveys were conducted over the 20-month curriculum timeframe. Results The needs assessment revealed that there were no pre-existing MA continuing education didactics, but all (100%) MAs surveyed were “very interested” in such a curriculum. Sessions were found to be clear, comprehensive, relevant, and associated with a significant increase in a sense of empowerment (P = .035). Topics in Head and Neck and Breast Cancer showed large improvements in understanding (change in median Likert score of 3-4 points each) whereas topics in Introduction to Oncology and New Patient Consultation showed the smallest change (change 0.5-1). For 20 months, there was a sustained improvement in clinical understanding within and outside the scope of the MA role and an improvement in perceived empathy for patients (from median Likert score 3.5-5). Conclusions Dedicated education programs for MAs show the potential to improve clinical understanding and participation in patient care. Further studies may demonstrate how such programs translate to staff productivity or patient clinical outcomes. Interprofessional education may facilitate collaboration and enhanced clinical workflow.

PURPOSE/OBJECTIVE(S) Patients with large brain metastases may receive fractionated stereotactic radiosurgery (FSRS) if they are not surgical candidates yet still pursuing cancer-directed therapy. FSRS with limited margins can allow for optimal sparing of uninvolved regional brain tissue. However, due to required treatment planning process, there is often elapsed time between MRI brain and treatment start which may contribute to marginal misses. Growth rates of large brain metastases and implications for optimal margin to account for growth rate and time interval between planning MRI and FSRS are incompletely characterized. MATERIALS/METHODS Patients treated at a single institution from 2018-2020 who received frameless FSRS on a Cobalt-60 treatment unit for large (> 2cm diameter) brain metastases were identified. Patients with a prior diagnostic brain MRI scan with technically similar parameters to a second MRI obtained for treatment planning were included. Resection cavities and lesions undergoing re-treatment after prior SRS were excluded. Brain metastasis volumes were obtained by contouring on both diagnostic and planning MRIs. Patient characteristics and treatment details were also collected. Analysis was conducted using paired Student's t test and Pearson's R and growth rate was determined using a linear model. RESULTS Thirty-six patients with 54 brain metastases met inclusion criteria. The most common primary cancer sites were lung (36%), colorectal (14%), and skin (14%), and most common histologies were adenocarcinoma (53%) and melanoma (17%). Nearly half (47%) of patients were on systemic therapy at the time of FSRS and the majority (85%) received steroids prior to starting FSRS. Treatment dose ranged from 24-32.5 Gy in 3-5 fractions, with median of 30 Gy in 5 fractions with zero margin. Median time from diagnostic to planning MRI was 15 days (IQR: 11-21) and planning MRI to FSRS was 1 day (IQR 1-3). The median size of included brain metastases on planning MRI was 7.38cc (IQR: 5.09-11.55) compared to 6.03cc (IQR: 3.87-8.95) on prior diagnostic MRI (P 90% of lesions over 3, 7, 10, and 14 days between planning and treatment, respectively. CONCLUSION In the absence of expedited planning, FSRT for intact large brain metastases with limited margins may result in geometric under treatment. An adaptive margin strategy based upon initial tumor size, and time between planning imaging and treatment delivery may be afforded to maintain ideal conformity, properly targeting a growing target lesion while maximally sparing uninvolved regional brain. AUTHOR DISCLOSURE J. Chew: None. S. Sinha: None. S.J. Liu: None. S.E. Fogh: Independent Contractor; Accuray. L. Boreta: None. D. Raleigh: None. L. Ma: Patent/License Fees/Copyright; University of California Regents. S.E. Braunstein: Advisory Board; Radiation Oncology Questions, LLC.

PURPOSE/OBJECTIVE(S) Prior studies have demonstrated a survival benefit with the addition of adjuvant radiation therapy in patients with node-positive vulvar cancer after surgery. We sought to evaluate whether the survival benefit of adjuvant radiation therapy after surgery is maintained in elderly patients, who make up a large subgroup of patients with vulvar cancer. MATERIALS/METHODS The National Cancer Database was queried for patients 70 years of age or older, who were diagnosed with vulvar squamous cell carcinoma from 2004-2017 and underwent surgery with confirmed node-positive disease. Patients with unknown last follow-up date were excluded. Statistical analysis was performed with chi-square test, logistic regression analysis, log-rank test Kaplan-Meier, and multivariable Cox proportional regression modeling. RESULTS A total of 1,992 patients were analyzed, of which 1,216 (61.0%) received adjuvant radiotherapy with or without chemotherapy. Median follow-up was 73.0 months. Median age at diagnosis was 79 years (range 70-90). Five-year overall survival (OS) for the entire cohort was 28.0%. Five-year OS was 30.9% in patients who received adjuvant radiation and 23.4% in patients who did not receive adjuvant therapy (P < 0.0001). Multivariate analysis demonstrated a survival benefit associated with the addition of adjuvant radiotherapy (HR 0.77 [95% CI 0.69-00.86], P < 0.001) and chemotherapy (HR 0.86 [95% CI 0.77-0.96], P = 0.006). Among patients aged 70-84 years (N = 1555), adjuvant radiotherapy remained associated with improved overall survival (5-year OS 33.6% vs. 25.8%, P < 0.0001). However, in patients aged 85 years and older (N = 437), there was no significant difference in overall survival between patients who received adjuvant radiation versus those who did not receive adjuvant therapy (HR 0.91 [95% CI 0.74-1.12], P = 0.37), (5-year OS 16.8% vs. 18.3%, P = 0.36). CONCLUSION The results of this study suggest there is still a survival benefit associated with the addition of adjuvant radiotherapy in older patients with node-positive vulvar cancer treated with surgery. However, this benefit may be limited to patients under 85 years of age, and de-escalating therapy may be appropriate for a subset of elderly patients. AUTHOR DISCLOSURE L. Ni: None. S. Sinha: None. C. Phuong: None. L. Chen: None. I.J. Hsu: None. E.J. Yoshida: None.

Androgen deprivation therapy (ADT) to treat prostate cancer may be associated with an increased risk of dementia, but existing studies have shown conflicting results. Here we synthesize the literature on the association of ADT for the treatment of prostate cancer with dementia risk. We conducted a systematic review of articles reporting the outcome of dementia among individuals with prostate cancer in those exposed to ADT versus a lesser-exposed comparison group (for example, ADT versus no-ADT; continuous versus intermittent ADT) using PubMed (1966–present), Web of Science (1945–present), Embase (1966–present) and PsycINFO (1806–present). The search was undertaken on 4 December 2016 by two authors. We meta-analyzed studies reporting an effect estimate and controlling for confounding. Random- or fixed-effects meta-analytic models were used in the presence or absence of heterogeneity per the I2 statistic, respectively. Small study effects were evaluated using Egger and Begg’s tests. Nine studies were included in the systematic review. Seven studies reported an adjusted effect estimate for dementia risk. A random-effects meta-analysis of studies reporting any dementia outcome, which included 50 541 individuals, showed an increased risk of dementia among ADT users (hazard ratio (HR), 1.47; 95% confidence interval (CI), 1.08–2.00; P=0.02). We separately meta-analyzed studies reporting all-cause dementia (HR, 1.46; 95% CI, 1.05–2.02; P

IMPORTANCE: Neurosurgical resection represents an important management strategy for patients with large, symptomatic brain metastases and increasingly is followed by stereotactic radiation as opposed to whole-brain radiation. Whether neurosurgical resection is associated with tumor spread beyond the resection site and adjuvant stereotactic radiation field remains unknown. OBJECTIVE: To characterize the association and incidence of pachymeningeal seeding with neurosurgical resection in patients with brain metastases treated with adjuvant stereotactic radiation. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of a consecutive sample of patients with newly diagnosed brain metastases managed with neurosurgical resection and stereotactic radiation (n = 318) vs radiation alone (n = 870) between 2001 and 2015. MAIN OUTCOMES AND MEASURES: Incidence of pachymeningeal seeding (dural and/or outer arachnoid) and leptomeningeal disease in patients treated with neurosurgical resection and stereotactic radiation vs radiation alone and the risk factors and outcomes associated with pachymeningeal seeding in patients treated with neurosurgical resection followed by stereotactic radiation. RESULTS: In 1188 patients with newly diagnosed brain metastases, 133 men and 185 women (mean [SD] age, 58.9 [11.5] years) underwent neurosurgical resection. Resection was found to be associated with pachymeningeal seeding (36 of 318 patients vs 0 of 870 patients; P

Objectives/Hypothesis 1) Determine feasibility of smartphone-based mobile technology to measure noise exposure; and 2) measure noise exposure in exercise spin classes. Study Design Observational Study. Methods The SoundMeter Pro app (Faber Acoustical, Salt Lake City, UT) was installed and calibrated on iPhone and iPod devices in an audiology chamber using an external sound level meter to within 2 dBA of accuracy. Recording devices were placed in the bike cupholders of participants attending spin classes in Boston, Massachusetts (n = 17) and used to measure sound level (A-weighted) and noise dosimetry during exercise according to National Institute for Occupational Safety and Health (NIOSH) guidelines. Results The average length of exposure was 48.9 ± 1.2 (standard error of the mean) minutes per class. Maximum sound recorded among 17 random classes was 116.7 dBA, which was below the NIOSH instantaneous exposure guideline of 140 dBA. An average of 31.6 ± 3.8 minutes were spent at >100 dBA. This exceeds NIOSH recommendations of 15 minutes of exposure or less at 100 dBA per day. Average noise exposure for one 45-minute class was 8.95 ± 1.2 times the recommended noise exposure dose for an 8-hour workday. Conclusions Preliminary data shows that randomly sampled cycling classes may have high noise levels with a potential for noise-induced hearing loss. Mobile dosimetry technology may enable users to self-monitor risk to their hearing and actively engage in noise protection measures. Level of Evidence NA Laryngoscope, 127:1873–1877, 2017

Patients with head and neck cancer who undergo reconstructive surgery are at risk for deep venous thrombosis (DVT), but the risk profile for patients undergoing major flap reconstruction is highly variable. Herein, we report our findings from a retrospective analysis of head and neck cancer patients (n = 517) who underwent free (n = 384) or pedicled (n = 133) flap reconstructive operations at a major tertiary care center from 2011 to 2014. DVTs developed perioperatively in 9 (1.7%) patients. Compared with pedicled flap patients, free flap patients had a longer mean operative time (421.4 ± 4.4 vs 332.7 ± 10.7 min, P < .0001), but the DVT incidence did not differ significantly between free and pedicled flap patients (1.6% vs 2.2%, respectively, P = .28). These data suggest that perioperative DVT risk in head and neck oncology patients may be largely similar regardless of the reconstructive strategy pursued.

Objectives Review outcomes of lateral temporal bone resections for ear and temporal bone malignancy. Design, Setting, and Participants Retrospective review of all lateral temporal bone resections performed from 2008 to 2015 at a single tertiary care center. Main Outcome Measures Patient demographics, perioperative variables, overall survival, disease-free survival (DFS), and comparison of Kaplan–Meier curves. Results Overall, 56 patients were identified with a mean follow-up period of 2.3 ± 1.8 years. The predominant histopathologic diagnosis was squamous cell carcinoma (SCC, 54%), followed by salivary gland tumors (18%), and basal cell carcinoma (9%). Tumor stages were T1-T2 in 23%, T3-T4 in 73%, and two unknown primary lesions. Mean overall survival was 4.6 ± 0.4 years. Comparison of tumors with and without lymph node involvement or perineural invasion approached statistical significance for overall survival ( p = 0.07 and 0.06, respectively). DFS was 2.5 ± 0.3 years. Stratification by lymph node status had a statistically significant difference in DFS ( p = 0.03). Subgroup analysis of SCC patients did not reveal significant differences. Conclusions Based on our cohort, most patients with temporal bone malignancies present with advanced disease, making it difficult to achieve negative margins. Overall, lymph node status was the strongest predictor of survival in this group.

Purpose/Objective(s): Tertiary radiation oncology centers receive referrals from diverse care settings, including private facilities, Veteran’s Affair (VA) hospitals, and county hospitals. An exploratory study of county patients treated at our institution identified that each missed consult or simulation (sim) appointment was associated with a greater than three-week delay from referral to radiation (RT) start. We sought to validate this in a larger sample and compared RT referral-to-start timelines for a variety of referral streams. Materials and Methods: Up to 60 consecutively referred patients from each facility (internal health system, VA, county hospital, and external private facilities) between June to December 2018 were included. Primary disease site, interpreter requirements, and dates of referral, consultation, sim, and RT start were recorded. Linear regression and analysis of variance models were developed to identify variables associated with delays in RT. Results: Of 214 patients were included; 55 (26%) internal, 53 (25%) from the VA, 60 (29%) from the county hospital, and 46 (22%) from other facilities. Among the 33 patients requiring interpreters, 28 (85%) were county patients. The most common referrals were for genitourinary (GU) cancers (n = 63, 29%), followed by breast (n = 29, 14%), lung (n = 26, 12%), and head and neck (n = 21, 10%) cancers. The median days from referral to consult was 16 (IQR 7-28), with the shortest time to consult for bone (1.5 days, IQR 1-5) and central nervous system sites (5 days, IQR 3-9) and the longest for gynecologic cancers (21.5 days, IQR 8.5-44). Excluding GU patients, who often require two months of neoadjuvant hormone therapy prior to RT, the median days from consult to sim was 13 (IQR 6-20) with no significant differences in referral to consult or consult to sim by referring facility. In all patients, the median days from sim to RT start was 8 (IQR 6-14) with no significant differences by referral facility. In univariate analysis among non-GU patients, referring facility and requirement of an interpreter were not associated with referral-to-start delays; only missing one or more consult/sim appointments was significant (p < 0.001). Each missed appointment was associated with a 37-day delay (95% CI 26 – 48) in referral-to-start. Conclusion: In a patient cohort with heterogeneous cancer diagnoses, no facility-specific delays were identified despite county hospital patients having known socioeconomic vulnerability. Efforts to decrease RT delays may require department-wide, as opposed to interfacility, interventions. Future goals involve using site-specific referral-to-start benchmarks (e.g. one week for palliation and 10 weeks for GU) to further discriminate differences. Citation Format: Melody J Xu, Sumi Sinha, Sunny Wang, Terence Friedlander, Steve E Braunstein. Comparison of radiation therapy initiation timelines among varied referral streams to identify sources of delay [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A133.

Blood product utilization is monitored to prevent unnecessary transfusions. Head-and-neck pedicled flap reconstruction transfusion-related outcomes were assessed.One hundred and thirty-six pedicled flap patients were reviewed: 64 supraclavicular artery island flaps (SCAIF), 57 pectoralis major (PM) flaps, and 15 submental (SM) flaps. Outcome parameters included flap-related complications, medical complications, length of stay (LOS), and flap survival. Multivariable logistic regression analyses were performed. Multivariable logistic regression analyses were performed to adjust for relevant pre- and perioperative factors.Of all head-and-neck pedicled flap patients included in our analyses (n = 136), 40 (29.4%) received blood transfusions. The average pretransfusion hematocrit (Hct) was 24.3% ± 0.5%, with 2.65 ± 0.33 units transfused and a posttransfusion Hct increase of 5.0% ± 0.6%. Transfusion rates differed with PM (47.4%), SCAIF (17.2%), and SM (13.3%) flaps (P 0.005). Patients undergoing PM reconstruction trended toward higher transfusion requirements (PM 2.89 ± 0.47 units, SC 2.18 ± 0.28 units, and SM 2.00 ± 0.0 units), with transfusion occurring later in the postoperative course (4.9 ± 1.3 days vs. 2.4 ± 0.1 days for all other flaps; P = 0.08). Infection, dehiscence, fistula, or medical complications were not different. Transfusion thresholds of Hct 21 versus Hct 27 exhibited no difference in LOS, flap-survival, or medical/flap-related complications.Transfusion is not associated with surgical or medical morbidity following head and neck pedicled flap reconstruction. There were no differences in outcomes between transfusion triggers of Hct 21 versus Hct 27, suggesting that a more conservative transfusion trigger may not precipitate adverse patient complications. Our data recapitulate findings in free flap patients and warrant further investigation of transfusion practices in head and neck flap reconstruction.4. Laryngoscope, 128:E409-E415, 2018.

Background There is increasing evidence that androgen deprivation therapy (ADT) may be associated with depression. Existing studies have shown conflicting results. Methods PubMed, Web of Science, Embase, and PsycINFO were queried on April 5, 2017. Eligible studies were in English and reported depression among individuals with prostate cancer exposed to a course of ADT vs. a lesser-exposed group (e.g., any-ADT vs. no ADT and continuous ADT vs. intermittent ADT). We used the MOOSE statement guidelines and the Cochrane Review Group’s data extraction template. Study quality was evaluated by Newcastle-Ottawa Scale criteria. We conducted a random-effects meta-analysis to calculate summary statistic risk ratios (RRs) and 95% CIs. Heterogeneity was quantified using the I 2 statistic and prespecified subgroup analysis. Small study effects were evaluated using Begg and Egger statistics. Results A total of 1,128 studies were initially identified and evaluated. A meta-analysis of 18 studies among 168,756 individuals found that ADT use conferred a 41% increased risk of depression (RR = 1.41; 95% CI: 1.18–1.70; P P = 0.005) and those using a clinical diagnosis of depression (RR = 1.19; 95% CI: 1.08–1.32; P = 0.001). We did not find an association for continuous ADT with depression risk compared to intermittent ADT (RR = 1.00; 95% CI: 0.50–1.99; P = 0.992). There was no statistically significant evidence of small study effects. Statistically significant heterogeneity in the full analysis ( I 2 = 80%; 95% CI: 69–87; P I 2 = 16%; 95% CI: 0–60; P = 0.310). Conclusion The currently available evidence suggests that ADT in the treatment of prostate cancer is associated with an increased risk of depression.

BackgroundWe sought to determine temporal trends in the receipt of prostatectomy or locoregional radiation to the prostate for patients with metastatic prostate cancer and to identify predictors of receipt of local treatment.MethodsWe identified 39,976 patients with metastatic prostate cancer diagnosed in 2004-2012 using the National Cancer Database (NCDB). We used logistic multivariable regression to determine trends in the receipt of prostate and/or pelvic radiation or radical prostatectomy after adjusting for demographic and clinical factors.ResultsPatients with metastatic disease were less likely to receive locoregional treatment over time [7.88% in 2004 vs. 5.53% in 2012, adjusted odds ratio (AOR) = 0.97 per year, 95% confidence interval (CI) = 0.95-0.98; P

Patients with head and neck cancer who undergo reconstructive surgery are at risk for deep venous thrombosis (DVT), but the risk profile for patients undergoing major flap reconstruction is highly variable. Herein, we report our findings from a retrospective analysis of head and neck cancer patients (n = 517) who underwent free (n = 384) or pedicled (n = 133) flap reconstructive operations at a major tertiary care center from 2011 to 2014. DVTs developed perioperatively in 9 (1.7%) patients. Compared with pedicled flap patients, free flap patients had a longer mean operative time (421.4 ± 4.4 vs 332.7 ± 10.7 min, P.0001), but the DVT incidence did not differ significantly between free and pedicled flap patients (1.6% vs 2.2%, respectively, P = .28). These data suggest that perioperative DVT risk in head and neck oncology patients may be largely similar regardless of the reconstructive strategy pursued.

Surgical simulators are designed to improve operative skills and patient safety. Transcanal Endoscopic Ear Surgery (TEES) is a relatively new surgical approach with a slow learning curve due to one-handed dissection. A reusable and customizable 3-dimensional (3D)-printed endoscopic ear surgery simulator may facilitate the development of surgical skills with high fidelity and low cost. Herein, we aim to design, fabricate, and test a low-cost and reusable 3D-printed TEES simulator.The TEES simulator was designed in computer-aided design (CAD) software using anatomic measurements taken from anthropometric studies. Cross sections from external auditory canal samples were traced as vectors and serially combined into a mesh construct. A modified tympanic cavity with a modular testing platform for simulator tasks was incorporated. Components were fabricated using calcium sulfate hemihydrate powder and multiple colored infiltrants via a commercial inkjet 3D-printing service.All components of a left-sided ear were printed to scale. Six right-handed trainees completed three trials each. Mean trial time (n = 3) ranged from 23.03 to 62.77 s using the dominant hand for all dissection. Statistically significant differences between first and last completion time with the dominant hand (p 0.05) and average completion time for junior and senior residents (p 0.05) suggest construct validity.A 3D-printed simulator is feasible for TEES simulation. Otolaryngology training programs with access to a 3D printer may readily fabricate a TEES simulator, resulting in inexpensive yet high-fidelity surgical simulation.