Search

Purpose Characterize the clinical outcomes of endometrial cancer vaginal recurrences after previous surgery and radiation therapy treated with reirradiation including image-guided interstitial high-dose-rate (HDR) brachytherapy. Methods and materials A single-institution retrospective study identifying women receiving reirradiation for vaginal recurrence of endometrial cancer between 2004 and 2017. Results Twenty-three women had vaginal recurrences of endometrial cancer, median 13.7 months (range 3.5–104.9) from initial radiation. All received reirradiation with interstitial HDR brachytherapy, and seven also received external beam radiation. Median reirradiation EQD2_10 was 48 Gy (range 24.0–68.81), and median cumulative EQD2_10 was 106.25 Gy (range 62.26–122.0). Median follow-up after reirradiation was 40.2 months (range 4.5–112.7). At 3 years, overall survival was 56%, cancer-specific survival was 61%, and disease-free survival was 46%. 14 patients experienced disease recurrence; 10 including distant sites, one at a regional node only. Three patients experienced local recurrences, two of whom did not complete the prescribed course of reirradiation. The overall crude local control rate was 87%. Three patients experienced Grade 3 vaginal toxicity. There was no bladder or rectal toxicity with Grade >2. Conclusions Reirradiation including interstitial HDR brachytherapy is a promising option for vaginal recurrences of endometrial cancer after prior radiation, with high rate of local control and acceptable toxicity. However, distant failure is common. Further studies are needed to determine cumulative radiation dose limits and the role of systemic therapy in this scenario.

Objectives Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause community-acquired acute kidney injury, especially in high-risk populations. Both the U.S. Food and Drug Administration (FDA) medication guide and over-the-counter labeling vaguely describe kidney risks of NSAIDs and do not provide information for patients to evaluate their risk for kidney problems. The purpose of this study was to use a mobile application to evaluate the impact of patient choice of media delivering NSAID avoidance education on patient knowledge about kidney risks associated with NSAIDs. Design Prospective cohort study. The mobile application was used to deliver either a redesigned FDA medication guide or a video focused on NSAID risks (selected by the patient), followed by patient knowledge questions (PKQs) and a kidney risk assessment. Setting and participants One hundred fifty adult primary care patients in southeast Michigan. Main outcome measures The primary outcome was the score on 5 NSAID PKQs between the media selected. Secondary outcomes included characterization of media choice among different demographic and NSAID kidney risk groups. The relationship between kidney risk assessment and self-reported NSAID avoidance behavior also was evaluated. Results The majority of participants (72.7%) chose to review print material. Those that chose print had significantly higher PKQ scores (5 total points) compared with participants who selected the video: mean scores 4.2 ± 0.9 with print and 3.8 ± 1.0 with video (P = 0.034). Older patients (>65 years) had significantly lower PKQ scores compared with other age groups. Forty-four percent of individuals (n = 66) reported current NSAID use, and 65% stated that they would avoid NSAIDs after the selected education material. Conclusion Scores for questions related to NSAID kidney risk knowledge were higher among participants who chose print compared with video education material. Education regarding NSAID kidney risks encouraged patients to limit their use. Targeted education may be beneficial in high-risk (e.g., older) patients and should be further studied.

Background Optimal techniques and patient selection for salvage reirradiation of high-grade glioma (HGG) are unclear. In this study, we identify prognostic factors for freedom from progression (FFP) and overall survival (OS) after reirradiation, risk factors for high-grade toxicity, and validate clinical prognostic scores. Methods A total of 116 patients evaluated between 2000 and 2018 received reirradiation for HGG (99 WHO grade IV, 17 WHO grade III). Median time to first progression after initial therapy was 10.6 months. Salvage therapies before reirradiation included surgery (31%) and systemic therapy (41%). Sixty-five patients (56%) received single-fraction stereotactic radiosurgery (SRS) as reirradiation. The median biologically effective dose (BED) was 47.25 Gy, and the median planning target volume (PTV) was 4.8 cc for SRS and 95.0 cc for non-SRS treatments. Systemic therapy was given concurrently to 52% and adjuvantly to 74% of patients. Results Median FFP was 4.9 months, and median OS was 11.0 months. Significant multivariable prognostic factors for FFP were performance status, time to initial progression, and BED; for OS they were age, time to initial progression, and PTV volume at recurrence. High-grade toxicity was correlated to PTV size at recurrence. Three-level prognostic scores were generated for FFP and OS, with cross-validated receiver operating characteristic area under the curve (AUC) of 0.640 and 0.687, respectively. Conclusions Clinical variables at the time of reirradiation for HGG can be used to prognosticate FFP and OS.

Author(s): Wu, Susan Y; Yee, Emily; Chan, Jason W; Chapman, Christopher H; Boreta, Lauren; Braunstein, Steve E | Abstract: PurposeUrgent indications for palliative radiation therapy (RT) include malignant spinal cord compression, symptomatic brain metastases, pain, airway obstruction, and bleeding. Data on the timing of palliative RT in the inpatient setting are limited. We report our experience with inpatient palliative RT at a tertiary academic center and evaluate the effect of a dedicated inpatient palliative RT nurse practitioner (NP) on treatment timelines.Methods and materialsWe performed a retrospective, single-institution review of 219 inpatients consulted for RT to sites of metastatic disease between May 2012 and May 2018. We compared time-to-treatment intervals before and after integrating an NP for palliative RT in Augustn2017.ResultsThe median age of the 219 patients receiving RT was 61 years (interquartile range [IQR], 51-69 years). The most frequent indications were symptomatic brain metastases (73 patients [33%]), pain (61 patients [28%]), and cord/cauda compression (48 patients [22%]). The median time from consultation request to consult was 1 day (IQR, 0-2 days), and the median time from consultation request to first RT fraction was 3 days (IQR, 2-6 days). The median time from consultation request to RT was shorter for cord compression (2 [IQR, 1-4] days) than for pain (5 [IQR, 2-7] days) (P = .001) or symptomatic brain metastases (3 [IQR, 1-6] days; P = .037). With an NP, patients were more likely to undergo same-day consultation and simulation (75% vs 60%; P = .045), which was associated with shorter median duration from consultation to initiation of RT (1 [IQR, 0-3] days vs 4 [IQR, 2-7] days; P l.001). After the integration of an NP for palliative RT, patients had a higher median Karnofsky Performance Score (70 [IQR, 60-80] vs 50 [IQR, 40-60]; P l .001) and were more likely to complete their prescribed RT course (93% vs 82%; P = .05).ConclusionsTime from consultation request to RT is necessarily short for urgent inpatient palliative RT. Advanced practice providers may facilitate and potentially expedite treatment, with significantly shorter times to treatment among patients who undergo same-day consultation and simulation.

OBJECTIVES/HYPOTHESIS Squamous cell carcinoma of the hypopharynx (SCCHP) is associated with worse survival compared to other head and neck subsites. This report quantifies the impact of technological improvements in radiotherapy (RT) on outcomes over 6 decades. METHODS Patients with SCCHP receiving curative-intent treatment between 1962 and 2015 were retrospectively reviewed. Kaplan-Meier analyses of freedom from local recurrence (FFLR), progression-free survival (PFS), and overall survival (OS) were compared across treatment eras and radiation techniques. Multivariable Cox proportional hazards modeling was performed to specify the effect of RT technique. RESULTS One hundred thirty-four patients had a median follow-up of 17 months (IQR = 9-38). There were no differences in staging or use of surgery over time, but use of chemotherapy concurrent with RT increased (P

Author(s): Chapman, Christopher H; Braunstein, Steve E; Pouliot, Jean; Noworolski, Susan M; Weinberg, Vivian; Cunha, Adam; Kurhanewicz, John; Gottschalk, Alexander R; Roach, Mack Iii; Hsu, I-Chow | Abstract: PurposeRadiation dose escalation for prostate cancer improves biochemical control but is limited by toxicity. Magnetic resonance spectroscopic imaging (MRSI) can define dominant intraprostatic lesions (DIL). This phase I study evaluated dose escalation to MRSI-defined DIL using high-dose-rate (HDR) brachytherapy.Material and methodsEnrollment was closed early due to low accrual. Ten patients with prostate cancer (T2a-3b, Gleason 6-9, PSA l 20) underwent pre-treatment MRSI, and eight patients had one to three DIL identified. The eight enrolled patients received external beam radiation therapy to 45 Gy and HDR brachytherapy boost to the prostate of 19 Gy in 2 fractions. MRSI images were registered to planning CT images and DIL dose-escalated up to 150% of prescription dose while maintaining normal tissue constraints. The primary endpoint was genitourinary (GU) toxicity.ResultsThe median total DIL volume was 1.31 ml (range, 0.67-6.33 ml). Median DIL boost was 130% of prescription dose (range, 110-150%). Median urethra V120 was 0.15 ml (range, 0-0.4 ml) and median rectum V75 was 0.74 ml (range, 0.1-1.0 ml). Three patients had acute grade 2 GU toxicity, and two patients had late grade 2 GU toxicity. No patients had grade 2 or higher gastrointestinal toxicity, and no grade 3 or higher toxicities were noted. There were no biochemical failures with median follow-up of 4.9 years (range, 2-8.5 years).ConclusionsDose escalation to MRSI-defined DIL is feasible. Toxicity was low but incompletely assessed due to limited patients' enrollment.

Purpose To evaluate clinical outcomes for isolated vaginal recurrence of endometrial cancer without adjuvant therapy treated with salvage external beam radiation therapy (EBRT) and high-dose-rate CT-based inverse-planned brachytherapy. Methods and Materials Thirty women were included in this retrospective study. Median time to first recurrence was 16.7 months, and median age at recurrence was 73 years. Initial grade was 1 or 2 in 19 patients (63%), and 2009 FIGO stage IA in 19 patients. All patients received pelvic EBRT in 1.8 Gy daily fractions to a total of 45 or 50.4 Gy. Interstitial brachytherapy was used in 27 patients (90%). The median total EQD2 dose was 68.3 Gy. Kaplan-Meier estimates of overall survival (OS), cause-specific survival (CSS), progression free survival (PFS), locoregional failure-free survival, and distant failure–free survival (DFFS) were calculated. Results Median follow-up was 76.4 months for vital status and 57.7 months for disease status after salvage therapy. The 5-year OS, CSS, PFS, locoregional failure-free survival, and DFFS after salvage therapy were 77%, 83%, 75%, 87%, and 86%. Initial high-grade disease was prognostic for OS, CSS, and DFFS (5-year OS 95% vs. 29%, p = 0.005). Initial stage beyond IA was prognostic for CSS, PFS, and DFFS (5-year CSS 93% vs. 74%, p = 0.025). Conclusions Salvage EBRT and high-dose-rate brachytherapy resulted in a high rate of locoregional control. Initial high-grade and advanced stage disease were associated with greater distant failure and cancer-related mortality after salvage therapy.

Author(s): Chapman, Christopher H; McGuinness, Christopher; Gottschalk, Alexander R; Yom, Sue S; Garsa, Adam A; Anwar, Mekhail; Braunstein, Steve E; Sudhyadhom, Atchar; Keall, Paul; Descovich, Martina | Abstract: Purpose/objectivesFor lung stereotactic body radiation therapy (SBRT), real-time tumor tracking (RTT) allows for less radiation to normal lung compared to the internal target volume (ITV) method of respiratory motion management. To quantify the advantage of RTT, we examined the difference in radiation pneumonitis risk between these two techniques using a normal tissue complication probability (NTCP) model.Materials/method20 lung SBRT treatment plans using RTT were replanned with the ITV method using respiratory motion information from a 4D-CT image acquired at the original simulation. Risk of symptomatic radiation pneumonitis was calculated for both plans using a previously derived NTCP model. Features available before treatment planning that identified significant increase in NTCP with ITV versus RTT plans were identified.ResultsPrescription dose to the planning target volume (PTV) ranged from 22 to 60 Gy in 1-5 fractions. The median tumor diameter was 3.5 cm (range 2.1-5.5 cm) with a median volume of 14.5 mL (range 3.6-59.9 mL). The median increase in PTV volume from RTT to ITV plans was 17.1 mL (range 3.5-72.4 mL), and the median increase in PTV/lung volume ratio was 0.46% (range 0.13-1.98%). Mean lung dose and percentage dose-volumes were significantly higher in ITV plans at all levels tested. The median NTCP was 5.1% for RTT plans and 8.9% for ITV plans, with a median difference of 1.9% (range 0.4-25.5%, pairwise P l 0.001). Increases in NTCP between plans were best predicted by increases in PTV volume and PTV/lung volume ratio.ConclusionsThe use of RTT decreased the risk of radiation pneumonitis in all plans. However, for most patients the risk reduction was minimal. Differences in plan PTV volume and PTV/lung volume ratio may identify patients who would benefit from RTT technique before completing treatment planning.

We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT).Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K(trans), and the fraction of blood plasma volume, Vp. The temporal changes in the means of hippocampal transfer constant K(trans) and Vp after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT.The mean K(trans) Increased significantly from pre-RT to 1-month post-RT (P.0004), which significantly depended on sex (P.0007) and age (P.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=-0.95, P.0006) and 18-months (r=-0.88, P.02) post-RT.The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.

SummaryBackground The objectives of this curricular innovation project were to implement a flipped classroom curriculum for the gynaecologic oncology topics of the obstetrics and gynaecology medical student clerkship, and to evaluate student satisfaction with the change. Methods Four short online videos on the topics of endometrial hyperplasia, cervical dysplasia, evaluation of an adnexal mass, and ovarian cancer were created, and students were instructed to view them prior to a class-time active learning session. The Learning Activity Management System (lams) open-source online platform was used to create an active learning class-time activity that consisted of a coached discussion of cases. Student satisfaction with the two aspects of the flipped curriculum was obtained. In addition, lecture assessment for the gynaecologic oncology topics and aggregate student performance on the gynaecological oncology questions of the US National Board of Medical Examiners (NBME) Subject Examination were compared before and after implementation of the curriculum. Results Eighty-nine students rotated on the clerkship during the pilot period of analysis. Seventy-one students (80%) viewed the videos prior to the class session, and 84 (94%) attended the session. Student satisfaction was very high for both parts of the curriculum. There was no significant difference in aggregate student performance on the gynaecological oncology questions of the NBME Subject Examination. The flipped classroom curriculum demonstrates a promising platform for using technology to make better use of students’ time Discussion Our implementation of the flipped classroom curriculum for the gynaecologic oncology topics successfully demonstrates a promising platform for using technology to make better use of our students’ time, and for increasing their satisfaction with the necessary didactic learning of the clerkship.

Design Thinking is an approach used by designers to systematically design products ranging from buildings to appliances to websites [1]. Design Thinking allows designers to collaborate with clients, users, and nondesigners in the design process [2,3]. In the case of the medical student-run journal launched at the University of Michigan, Michigan Journal of Medicine (MJM), we employed a design thinking process to work closely with the MJM faculty subject matter experts and student editors to design the journal website in an efficient and effective manner. This chapter presents our overall design process and the ways we specifically applied it to the design of the MJM web presence. This same process can easily be adapted to laboratory websites, patient portals, and other products for the dissemination of medical and scholarly content.

This chapter will discuss the management of salivary gland tumors of the head and neck, with an emphasis on radiation therapy technique and published data.

This chapter will discuss the epidemiology, workup, and management of larynx and hypopharynx cancer, with an emphasis on radiation therapy technique and randomized trial evidence.

This chapter will discuss the epidemiology, workup, and management of oral cavity cancer, with an emphasis on radiation therapy technique (including brachytherapy) and randomized trial evidence.

Introduction Cardiac auscultation is an important clinical skill used by health care professionals during bedside patient evaluation and management. To support development of this skill in health sciences students, we created a self-paced, interactive program. This program helps develop foundational skills and knowledge so learners can confidently perform basic cardiac auscultation at the bedside. Methods For novice learners, this program should be used in conjunction with their initial clinical experiences so they can immediately apply what they have learned in the short course. Advanced learners and health care professionals can use this program to review and improve their cardiac auscultation skills. To achieve these objectives, this multimedia program teaches the eight basic heart cadences and their clinical significance through the use of guided tutorials, a gamified e-learning activity, interactive clinical cases, and a self-assessment. A heart sound and murmur library is also included for comparative listening at the bedside. Results Course evaluations from the first- and second-year Clinical Foundations of Medicine courses at the University of Michigan Medical School demonstrate the value of the various sections of the program. Additionally, the clinical cases have been shown to be effective in improving cardiac auscultation knowledge and skills among residents. Discussion All clinical cases in the program are based on authentic clinical problems and were developed by academic cardiologists and internists with expertise in this area. Various sections of this tutorial have been in use at our institution for over 20 years and have been evaluated favorably by our students.

Introduction Poor prescribing is probably the most common cause of preventable medication errors and many of these events involve junior doctors. In 2009, an electronic problem-based therapeutics course developed at the University of Michigan Medical School (UMMS) was translated and adapted for use at the University of Zagreb Medical School (UZMS). Methods After students from both schools took the course in 2010, we compared their responses with an online questionnaire addressing the course quality and its effectiveness. Results There were no statistically significant differences in the overall average grades awarded for the course (UZMS 4.11 ± 0.86 vs. UMMS 3.96 ± 0.93; 95% CI mean difference (MD) – 0.36, 0.07; P = 0.175) with both student groups expressing high satisfaction rates with its quality, accessibility and overall design. UZMS students reported spending less time working through the course than their American colleagues (2.14 ± 1.01 vs. 2.89 ± 1.02 on a five point Likert scale; 95% CI MD 0.51, 0.99; P

Purpose/objectives Radiation injury to parahippocampal cingulum white matter is associated with cognitive decline. Diffusion tensor imaging (DTI) detects micropathologic changes in white matter. Increased radial diffusion (RD) and decreased axial diffusion (AD) correspond to demyelination and axonal degeneration/gliosis respectively. We aimed to develop a predictive model for radiation-induced cognitive changes based upon DTI changes. Materials/methods Twenty-seven adults with benign or low-grade tumors received partial brain radiation therapy (RT) to a median dose of 54Gy. Patients underwent DTI before RT, during RT, and at the end of RT. Cognitive testing was performed before RT, and 6 and 18months after RT. Parahippocampal cingulum white matter was contoured to obtain mean values of AD and RD. Results By univariate analysis, decreasing AD and increasing RD during RT predicted declines in verbal memory and verbal fluency. By multivariate analysis, baseline neurocognitive score was the only clinical variable predicting verbal memory change; no clinical variables predicted verbal fluency change. In a multivariate model, increased RD at the end of RT significantly predicted decline in verbal fluency 18months after RT. Conclusions Imaging biomarkers of white matter injury contributed to predictive models of cognitive function change after RT.

Purpose To report outcomes in patients treated with intensity-modulated radiotherapy (IMRT) for tumors of the paranasal sinuses and nasal cavity (PNS/NC). Methods/Materials Between June 2000 and December 2009, 52 patients with tumors of the PNS/NC underwent postoperative or definitive radiation with IMRT. Twenty-eight (54%) patients had squamous cell carcinoma (SCC). Twenty-nine patients (56%) received chemotherapy. The median follow-up was 26.6 months (range, 2.9–118.4) for all patients and 30.9 months for living patients. Results Eighteen patients (35%) developed local-regional failure (LRF) at median time of 7.2 months. Thirteen local failures (25%) were observed, 12 in-field and 1 marginal. Six regional failures were observed, two in-field and four out-of-field. No patients treated with elective nodal radiation had nodal regional failure. Two-year local-regional control (LRC), in-field LRC, freedom from distant metastasis (FFDM), and overall survival (OS) were 64%, 74%, 71%, and 66% among all patients, respectively, and 43%, 61%, 61%, and 53% among patients with SCC, respectively. On multivariate analysis, SCC and >1 subsite involved had worse LRC ( p = 0.0004 and p = 0.046, respectively) and OS ( p = 0.003 and p = 0.046, respectively). Cribriform plate invasion ( p = 0.005) and residual disease ( p = 0.047) also had worse LRC. Acute toxicities included Grade ≥3 mucositis in 19 patients (37%), and Grade 3 dermatitis in 8 patients (15%). Six patients had Grade ≥3 late toxicity including one optic toxicity. Conclusions IMRT for patients with PNS/NC tumors has good outcomes compared with historical series and is well tolerated. Patients with SCC have worse LRC and OS. LRF is the predominant pattern of failure.

93 Background: Approximately half of patients undergoing radiotherapy (RT) do so with palliative intent. Urgent indications for RT may include neurologic compromise, pain, or bleeding. While some practices have a dedicated palliative RT team, the majority utilize an “on-call” system with a rotating outpatient radiation oncologist. We report our experience with a dedicated nurse practitioner (NP) to assist with palliative RT workflow, with the goal of expediting patient care. Methods: 226 inpatients treated with RT to a site of metastatic disease from May 2012 to May 2018 were included. Since August 2017, an NP has helped expedite emergent RT referrals. Mann-Whitney U tests were used to compare days between steps in the treatment planning process before and after integration of an NP. Results: The median age at RT was 60 years (IQR 49–69). The most common primary sites were lung (26%) and breast (12%). The most common indication for RT was symptomatic brain metastases (SBM, 33% of patients), followed by pain (27%) and spinal cord compression or cauda equina syndrome (SCC) (21%). The median time from referral (defined as initial contact by the primary team) to consultation was one day (IQR 0-2), and from referral to RT was four days (IQR 2-6). Median time from referral to RT was shorter for SCC (two days, IQR 1-4.5) and SBM (three days, IQR 1–6), than pain (five days, IQR 2–8) (p = 0.001 and p = 0.015, respectively). 68% of patients with SCC (32/47) and 35% of patients with SBM (26/74) started RT within one day of consultation. With an NP, patients were more likely to undergo simulation (sim) the same day as consultation (74% vs. 58%, p = 0.03). Same day sim was more common in patients with neurologic deficits (SCC+SBM) than those without (87% vs. 62%, p = 0.02). In those with neurologic deficits, time from consultation to sim decreased from 0.85 to 0.23 days (p = 0.04) and time from sim to RT decreased from 2.7 to 1.8 days (approaching significance, p = 0.06). In patients treated for pain, time from consultation to RT was reduced from 6.3 to 2.1 days (p = 0.02). Conclusions: For practices without a dedicated palliative RT team, involvement of an NP can improve workflow and expedite urgent RT. Further research is needed to rigorously explore quality improvement in the delivery of palliative RT.

PURPOSE/OBJECTIVE(S): Identify prognostic factors for progression-free survival (PFS) and overall survival (OS) after reirradiation (re-RT) for recurrent high grade glioma (HGG). MATERIALS/ METHODS: Patients with HGG received re-RT from 2010 to present. PFS and OS prognostic variables were examined using Cox models. Receiver operative curve (ROC) analysis identified predictive thresholds for continuous variables. RESULTS: 58 patients received surgery and adjuvant radiation for HGG (51 grade IV, 7 grade III). The median time to first progression after initial radiation was 11 months. 36% received single fraction stereotactic re-RT (SRS) (median 18 Gy) and 64% received fractionated re-RT (median 35 Gy in 10 fractions). The median planning target volume (PTV) was 16.8 mL. The median biologically effective dose (BED10) of re-RT was 47 Gy (range 15–72). 50% received chemotherapy and 36% received bevacizumab concurrent to re-RT. Toxicity ≥ grade 3 was 7%. The median PFS after re-RT was 4.7 months and the median OS was 11 months. Lower PFS was significantly associated with shorter time to first progression, lower KPS, and lower re-RT dose. Lower OS was associated with shorter time to first progression, lower KPS, and larger PTV. Other factors were not significantly associated with PFS or OS. ROC analysis of time to first progression and re-RT dose showed best predictive thresholds at time > 12 months and BED10 > 42 Gy. CONCLUSIONS: Reirradiation was tolerated with infrequent high grade toxicity. PFS and OS after re-RT were both predicted by time to progression after initial radiation. Published prognostic scores have used total time from first to second radiation courses; however in our series the period from initial progression to re-RT did not add prognostic information. There was evidence for a dose threshold irrespective of radiotherapy technique. Use of chemotherapy and bevacizumab with re-RT were not associated with improved outcomes.

Objectives: Multiple sclerosis (MS) is a neurological disorder with a high burden on patient quality of life and medical rehabilitation services. Little is known about the acute hospitalization costs and characteristics. We examined the trends in MS hospitalizations from 1993 to 2006. Methods: The Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project was searched using the ICD-9 code 340 (MS). Diagnostic, treatment and administrative data were analyzed using basic statistical software. Results: A total of 288,454 hospital admissions with the primary diagnosis of MS occurred between 1993 and 2006, an average of 20,604 admissions annually. The percentage admitted from the emergency department (ED) increased from 19.4 to 60.0% during 1993–2006. The mean cost for each inpatient increased from USD 7,965 to 20,076. The percentage of discharges to home health care increased from 8.6 to 14.9%, and the percentage of discharges to nursing homes and rehabilitation services increased from 8.3 to 22.6%. In 2006, Medicaid patients were significantly more likely to be admitted from the ED (p < 0.001). Medicare payers were significantly more likely to be discharged to a nursing home/rehabilitation (p < 0.0001). Conclusion: National health insurance policies have made measurable effects on MS disease management. MS is becoming more expensive to treat acutely, and improved treatment modalities geared toward decreasing acute flare-ups may provide substantial cost savings by reducing ED visits, inpatient hospitalizations and the need for rehabilitation.

Previous efforts to decrease neurocognitive effects of radiation focused on sparing isolated cortical structures. We hypothesize that understanding temporal, spatial, and dosimetric patterns of radiation damage to whole-brain white matter (WM) after partial-brain irradiation might also be important. Therefore, we carried out a study to develop the methodology to assess radiation therapy (RT)-induced damage to whole-brain WM bundles.An atlas-based, automated WM tractography analysis was implemented to quantify longitudinal changes in indices of diffusion tensor imaging (DTI) of 22 major WM fibers in 33 patients with predominantly low-grade or benign brain tumors treated by RT. Six DTI scans per patient were performed from before RT to 18 months after RT. The DTI indices and planned doses (maximum and mean doses) were mapped onto profiles of each of 22 WM bundles. A multivariate linear regression was performed to determine the main dose effect as well as the influence of other clinical factors on longitudinal percentage changes in axial diffusivity (AD) and radial diffusivity (RD) from before RT.Among 22 fiber bundles, AD or RD changes in 12 bundles were affected significantly by doses (P.05), as the effect was progressive over time. In 9 elongated tracts, decreased AD or RD was significantly related to maximum doses received, consistent with a serial structure. In individual bundles, AD changes were up to 11.5% at the maximum dose locations 18 months after RT. The dose effect on WM was greater in older female patients than younger male patients.Our study demonstrates for the first time that the maximum dose to the elongated WM bundles causes post-RT damage in WM. Validation and correlative studies are necessary to determine the ability and impact of sparing these bundles on preserving neurocognitive function after RT.

Introduction This resource provides a flipped classroom curriculum for the topics of endometrial hyperplasia and cervical dysplasia. Early intervention for these two precancerous processes can significantly reduce disease morbidity and mortality. This resource was created for medical students rotating on the obstetrics and gynecology clerkship; however, it can be utilized for diverse health care professionals since these two medical issues are commonly seen by all women's health care providers. Methods The flipped classroom curricular design consists of a preclass assignment that provides knowledge content for the learner, followed by class-time application of the knowledge through active learning. The preclass assignment for this flipped classroom curriculum is two short videos, one on endometrial hyperplasia and one on cervical dysplasia and human papilloma virus. These videos utilize a combination of animation and text. The class-time case-based active learning activity is the discussion of two clinical patient cases that focus on the evaluation and management of endometrial hyperplasia and cervical dysplasia. Results This curriculum uses technology in a novel way that enables and empowers the instructor to focus on the learner. Student satisfaction has been very high with this method of teaching. In a postcurricular survey, 89% of students preferred the preclass videos over traditional lecture, and 96% of students preferred the class-time case discussion over traditional lecture format. Discussion We have successfully utilized the flipped classroom curriculum for the gynecologic oncologic topics of the obstetrics and gynecology medical student clerkship since February 2013. A pilot analysis of initial student satisfaction with the curriculum revealed high student satisfaction with both the preclass videos and the class-time case discussion.

Asymptotic methods provide an efficient way to compute seismograms in heterogeneous media. However, zeroth-order ray theory, the simplest of the asymptotic methods, often fails because of the presence of caustics. Maslov theory is an extension of zeroth-order ray theory, which gives a uniformly valid expression of the wavefield everywhere, including the caustics. This result is given in terms of an integral of ray data over one or two ray parameters. It is shown in this paper how geometrical arrivals are constructed in the one and two-parameter Maslov integrals.

A patient was referred for radiotherapy of histologically confirmed squamous cell carcinoma in the left upper lobe and a subcarinal lymph node, stage IIIA (T3N2M0). He tested human immunodeficiency virus-positive 16 years before (current CD4 count of 58 cells/ L). His antiretroviral regimen included 1250 mg nelfinavir every 12 hours and five other antiretrovirals. After extensive discussion regarding chemoradiotherapy versus radiation therapy alone, he declined chemotherapy. From his own review of the preclinical literature on nelfinavir as a radiosensitizer, he chose to discontinue his antiretroviral regimen and take nelfinavir alone at 3750 mg every 12 hours. Treatment planning positron emission tomographycomputed tomography revealed a 5.4 3.4 4.0 cm primary tumor with a 1.6 0.5 2.2 cm central necrotic cavity (Figure 1A). Intensity-modulated radiation therapy was planned to 74 Gy total in 37 daily fractions (Figure 1B). Radiotherapy began 5 days after increasing the nelfinavir dose. The patient received nine treatments (18 Gy) without toxicity. Positron emission tomography-computed tomography for adaptive replanning revealed primary tumor size decrease to 4.6 3.9 3.9 cm and maximum standardized uptake value decrease from 11 to 5.8. The central cavity now measured 2.7 1.7 2.2 cm and communicated with the left bronchus (Figure 1C). On that day, he experienced mild hemoptysis not requiring intervention. He received one more fraction on the following day, completing 20 Gy, after which he suffered fatal massive hemoptysis. Autopsy indicated hemorrhage into the left lower lung parenchyma. Gross examination identified no residual subcarinal node or primary tumor, which was replaced by a 7 4 4 cm cavity containing necrotic debris. A 1.5 1.5 cm erosion tracked from the cavity into the left main bronchus (Figure 2C). Histology revealed microscopic foci of squamous cell carcinoma with extensive necrosis around the cavity and in the erosion track (Figure 2B). The adjacent lung parenchyma, bronchial mucosa, blood vessels, and nerves lacked histologic evidence of radiation injury. Thus, it appeared that rapid tumor regression allowed bleeding through the erosion into the lung parenchyma, leading to asphyxiation.

Study Objectives: The flipped classroom is a curricular innovation with great potential in medical education. The primary objectives were to create a flipped classroom curriculum for a four-week residency preparation elective, and to examine knowledge gains for content delivered by the flipped classroom versus traditional lecture. The secondary objective was to determine student satisfaction with the curricular innovation.

A method is presented for the analysis of the transmitted and reflected transient elastodynamic wave field at a fracture that may be modeled as a linear slip interface. With this method, the space-time domain problem is first carried over to the transform domain by means of a temporal Laplace transformation and a two-dimensional, horizontal spatial Fourier transformation. Subsequently, for both the SH and the P/SV wave systems, expressions are determined for the transmitted and reflected wave fields at the interface. Afterward, a transformation back to the space-time domain is carried out. The method is capable of providing the exact transmitted and reflected waves (including the body wave, interface wave, and head wave contributions) that are caused by a spatially curved, incident wave field due to a point source. Moreover, it is especially designed to yield the time domain waveforms. Various exact numerical results are given. For the SH case, the directionally dependent filter behavior of the fracture i...

Background Survival of patients with brain metastasis particularly from historically more radio-resistant malignancies remains dismal. A phase I study of concurrent bortezomib and whole brain radiotherapy was conducted to determine the tolerance and safety of this approach in patients with previously untreated brain metastasis. Methods A phase I dose escalation study evaluated the safety of bortezomib (0.9, 1.1, 1.3, 1.5, and 1.7 mg/m2) given on days 1, 4, 8 and 11 of whole brain radiotherapy. Patients with confirmed brain metastasis were recruited for participation. The primary endpoint was the dose-limiting toxicity, defined as any ≥ grade 3 non-hematologic toxicity or grade ≥ 4 hematologic toxicity from the start of treatment to one month post irradiation. Time-to-Event Continual Reassessment Method (TITE-CRM) was used to determine dose escalation. A companion study of brain diffusion tensor imaging MRI was conducted on a subset of patients to assess changes in the brain that might predict delayed cognitive effects. Results Twenty-four patients were recruited and completed the planned therapy. Patients with melanoma accounted for 83% of all participants. The bortezomib dose was escalated as planned to the highest dose of 1.7 mg/m2/dose. No grade 4/5 toxicities related to treatment were observed. Two patients had grade 3 dose-limiting toxicities (hyponatremia and encephalopathy). A partial or minor response was observed in 38% of patients. Bortezomib showed greater demyelination in hippocampus-associated white matter structures on MRI one month after radiotherapy compared to patients not treated with bortezomib (increase in radial diffusivity +16.8% versus 4.8%; p = 0.0023). Conclusions Concurrent bortezomib and whole brain irradiation for brain metastasis is well tolerated at one month follow-up, but MRI changes that have been shown to predict delayed cognitive function can be detected within one month of treatment.

The purpose of this study is to evaluate repeatability coefficients of diffusion tensor indices to assess whether longitudinal changes in diffusion indices were true changes beyond the uncertainty for individual patients undergoing radiation therapy (RT). Twenty-two patients who had low-grade or benign tumors and were treated by partial brain radiation therapy (PBRT) participated in an IRB-approved MRI protocol. The diffusion tensor images in the patients were acquired pre-RT, week 3 during RT, at the end of RT, and 1, 6, and 18 months after RT. As a measure of uncertainty, repeatability coefficients (RC) of diffusion indices in the segmented cingulum, corpus callosum, and fornix were estimated by using test–retest diffusion tensor datasets from the National Biomedical Imaging Archive (NBIA) database. The upper and lower limits of the 95% confidence interval of the estimated RC from the test and retest data were used to evaluate whether the longitudinal percentage changes in diffusion indices in the segmented structures in the individual patients were beyond the uncertainty and thus could be considered as true radiation-induced changes. Diffusion indices in different white matter structures showed different uncertainty ranges. The estimated RC for fractional anisotropy (FA) ranged from 5.3% to 9.6%, for mean diffusivity (MD) from 2.2% to 6.8%, for axial diffusivity (AD) from 2.4% to 5.5%, and for radial diffusivity (RD) from 2.9% to 9.7%. Overall, 23% of the patients treated by RT had FA changes, 44% had MD changes, 50% had AD changes, and 50% had RD changes beyond the uncertainty ranges. In the fornix, 85.7% and 100% of the patients showed changes beyond the uncertainty range at 6 and 18 months after RT, demonstrating that radiation has a pronounced late effect on the fornix compared to other segmented structures. It is critical to determine reliability of a change observed in an individual patient for clinical decision making. Assessments of the repeatability and confidence interval of diffusion tensor measurements in white matter structures allow us to determine the true longitudinal change in individual patients.

Purpose There is little known about how brain white matter structures differ in their response to radiation, which may have implications for radiation-induced neurocognitive impairment. We used diffusion tensor imaging (DTI) to examine regional variation in white matter changes following chemoradiotherapy. Methods Fourteen patients receiving two or three weeks of whole-brain radiation therapy (RT) ± chemotherapy underwent DTI pre-RT, at end-RT, and one month post-RT. Three diffusion indices were measured: fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). We determined significant individual voxel changes of diffusion indices using tract-based spatial statistics, and mean changes of the indices within fourteen white matter structures of interest. Results Voxels of significant FA decreases and RD increases were seen in all structures (p

Purpose : To segment fiber tracts in the limbic circuit and to assess their sensitivity to radiation therapy (RT). Methods: Twelve patients with brain metastases who had received fractionated whole brainradiation therapy to 30 Gy or 37.5 Gy were included in the study. Diffusion weighted images were acquired pre-RT, at the end of RT, and 1-month post-RT. The fornix, corpus callosum, and cingulum were extracted from diffusion weighted images by combining fiber tracking and segmentation methods based upon characteristics of the fiber bundles. Cingulum was segmented by a seed-based tractography, fornix by a region of interests (ROI)-based tractography, and corpus callosum by a level-set segmentation algorithm. The radiation-induced longitudinal changes of diffusion indices of the structures were evaluated. Results: Significant decreases were observed in the fractional anisotropy of the posterior part of the cingulum, fornix, and corpus callosum from pre-RT to end of RT by –14.0%, –12.5%, and –5.2%, respectively (p < 0.001), and from pre-RT to 1-month post-RT by –11.9%, –12.8%, and –6.4%, respectively (p < 0.001). Moreover, significant increases were observed in the mean diffusivity of the corpus callosum and the posterior part of the cingulum from pre-RT to end of RT by 6.8% and 6.5%, respectively, and from pre-RT to 1-month post-RT by 8.5% and 6.3%, respectively. The increase in the radial diffusivity primarily contributed to the significant decrease in the fractional anisotropy, indicating that demyelination is the predominant radiation effect on the white matter structures. Conclusions: Our findings indicate that the fornix and the posterior part of the cingulum are significantly susceptible to radiation damage. We have developed robust computer-aided semiautomatic segmentation and fiber tracking tools to facilitate the ROI delineation of critical structures, which is important for assessment of radiation damage in a longitudinal fashion.

This resource is a part of a seven-module curriculum intended to provide teaching faculty caring for well newborns with accessible, approachable, easily delivered, hands-on tools for bedside teaching in the newborn nursery. The seven modules are linked. This module focuses on the demonstration of the Ballard Exam. The template for a Ballard examination is frequently not incorporated into electronic health records and is consequently not being performed as frequently and systematically at our institutions. Medical student, residents, and nursing students have less familiarity with the components of a Ballard examination and are less likely to be able to systematically assess infant gestational age in the absence of formal introduction to the topic. The video was produced as an educational tool by the authors and is used in nursing and physician education at our institutions. The checklist was added and modeled after a newborn physical examination checklist created for our medical students and residents. The checklist was trialed at University of Michigan and Oregon Health & Science University where it has been incorporated as a standard in resident education. Students found the video particularly helpful. The examination can be difficult for first time learners, in particular the neuromuscular maturity portion. Early learners may focus on the physical maturity portion. The video also allows for an opportunity to discuss hand hygiene in patient care. Hand hygiene is of critical importance in the care of all patients, but especially when caring for newborns.

Introduction This resource is a part of a seven module curriculum intended to provide teaching faculty caring for well newborns with accessible, approachable, easily delivered, hands-on tools for bedside teaching in the newborn nursery. The seven modules are linked. Methods This module focuses on acquiring the skills to complete a newborn physical examination. Also included is a guide to newborn reflexes. This checklist has been used for third-year medical students, pediatric, medicine-pediatric and family medicine interns, and physician assistant students at three different institutions. Results This checklist was evaluated by randomizing 22 medical students into one of two groups: students who received feedback using this checklist and students who received routine feedback without using this checklist (control group). At the end of their one week newborn rotation, students' newborn physical exam skills were assessed by a blinded pediatrician. Using the checklist, students were given a score (0 = not done, 1 = needs improvement, 2 = done). Students who had received feedback using this checklist had a higher average score on individual items (average score 1.72 vs. 1.55 for control group, not significant). Discussion Attending physicians found the checklists easy to understand and easy to use. They felt that the checklists improved the quality of the feedback that the students received by covering more areas and by focusing on specific points. This checklist has been part of the University of Michigan student and intern curriculum since 2008.

Purpose: To determine whether early assessment of cerebral white matter degradation can predict late delayed cognitive decline after radiotherapy (RT). Methods and Materials: Ten patients undergoing conformal fractionated brain RT participated in a prospective diffusion tensor magnetic resonance imaging study. Magnetic resonance imaging studies were acquired before RT, at 3 and 6 weeks during RT, and 10, 30, and 78 weeks after starting RT. The diffusivity variables in the parahippocampal cingulum bundle and temporal lobe white matter were computed. A quality-of-life survey and neuro-cognitive function tests were administered before and after RT at the magnetic resonance imaging follow-up visits. Results: In both structures, longitudinal diffusivity (lambda(parallel to)) decreased and perpendicular diffusivity (lambda(perpendicular to)) increased after RT, with early changes correlating to later changes (p 50% of cingula volume receiving >12 Gy had a greater increase in lambda(perpendicular to) at 3 and 6 weeks (p < .05). The post-RT changes in verbal recall scores correlated linearly with the late changes in cingulum lambda(parallel to) (30 weeks, p < .02). Using receiver operating characteristic curves, early cingulum lambda(parallel to) changes predicted for post-RT changes in verbal recall scores (3 and 6 weeks, p < .05). The neurocognitive test scores correlated significantly with the quality-of-life survey results. Conclusions: The correlation between early diffusivity changes in the parahippocampal cingulum and the late decline in verbal recall suggests that diffusion tensor imaging might be useful as a biomarker for predicting late delayed cognitive decline. (C) 2012 Elsevier Inc. (Less)

In 2002 the University of Michigan Medical School created a one-month course in advanced medical therapeutics (AMT). All senior medical students were required to complete the course. To provide some flexibility for students who were interviewing for residency positions the AMT course was created using a distance-learning model, and in the 2008-2009 academic year it was offered in a fully online format. The components of the course are weekly case-based modules, a weekly online seminar, quizzes based on modules and seminars, and a research project based on a therapeutic question. The paper discusses the development and components of the AMT course, a survey of fourth-year medical students who participated in the course between 2007 and 2010, and how the course evolved over three years. Keywords: medical students; online course (Published: 6 May 2011) Citation: Medical Education Online 2011, 16 : 5733 - DOI: 10.3402/meo.v16i0.5733

BACKGROUND: Pancreatic cancer is associated with mutations in the tumor suppressor gene cyclin-dependent kinase inhibitor 2A (p16INK4A), a regulator of the cell cycle and apoptosis. This study investigates whether immunohistochemical expression of p16INK4A as well as hypoxia markers and poly adenosine diphosphate-ribose polymerase (PARP) correlates with survival in patients with resected pancreatic adenocarcinoma. METHODS: Seventy-three patients with pancreatic adenocarcinoma who underwent curative resection at Stanford University were included. From the surgical specimens, a tissue microarray was constructed using triplicate tissue cores from the primary tumor and used for immunohistochemical staining for the following markers: carbonic anhydrase IX, dihydrofolate reductase, p16INK4A, and PARP1/2. Staining was scored as either positive or negative and percentage positive staining. Staining score was correlated with overall survival (OS) and progression-free survival (PFS). RESULTS: Of the markers tested, only immunohistochemical expression of p16INK4A correlated with clinical outcome. On univariate analysis, p16INK4A expression in the tumor was associated with improved OS (P = .038) but not PFS (P = .28). The median survival for patients with positive versus negative p16INK4A staining was 28.8 months versus 18 months. On multivariate analysis, p16INK4A expression was associated with improved OS (P = .026) but not PFS (P = .25). Age (P = .0019) and number of nodes involved (P = .025) were also significant for OS. Adjuvant chemotherapy and margin status did not correlate with OS or PFS. CONCLUSIONS: Expression of p16INK4A is associated with improved OS in patients with resected pancreatic adenocarcinoma. Further investigation is needed for validation, given conflicting data in the published literature. Cancer 2010. © 2010 American Cancer Society.

Introduction The majority of esophageal cancer is either adenocarcinoma (ACA) or squamous cell carcinoma (SCCA). Recent randomized trials suggest that definitive chemoradiotherapy may be equally effective as surgery. However, the responsiveness of ACA versus SCCA to radiotherapy (RT) has never been compared. This Surveillance Epidemiology and End Results registry analysis investigates whether survival differed between ACA and SCCA based on the treatment modality. Methods Patients with T2-4N0 or N+ SCCA and ACA in the cervical or thoracic esophagus diagnosed from 1983 to 2004 were obtained from the Surveillance Epidemiology and End Results database. Patients with multiple primary cancers, underwent a surgical procedure other than partial or total esophagectomy, had metastatic or T1N0 disease, or received RT that did not include external beam radiation were excluded. Patients were grouped according to treatment received: RT alone, preoperative RT, any surgery (regardless of use of RT), and surgery alone. Results A total of 4752 patients were included, 2680 (56%) had ACA and 2072 (44%) had SCCA. After adjusting for age, marital status, cost of living, and race, the overall survival (OS) and cause-specific survival was similar for all treatment groups except the RT-alone group where OS and SCC were superior for ACA. However, no difference in 3- and 5-year OS and cause-specific survival rates for all groups. Conclusions No difference in survival was seen between patients with ACA and SCCA across any of the major treatment modalities for esophageal cancer, suggesting that both histologies respond to treatment similarly.

Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans were performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p 1M post-RT was interacted with sex (p