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Coursework across the music education curriculum provides teacher educators an opportunity to introduce and reinforce a range of instructional practices (i.e., creating, performing, responding to, and connecting with music) into the music classroom. Although instrument techniques courses are a foundational part of an undergraduate music education curriculum, previous research suggests that preservice music educators perceive these courses to be less impactful on their future careers than other courses in the curriculum. To create meaningful and transferable learning experiences, music teacher educators can include elements of experimentation, mistake-making, and creativity in brass techniques courses to provide preservice music educators with opportunities for independent learning and problem-solving. By offering these pedagogical techniques, music teacher educators can also model constructivist practices for students to use in their future classrooms.

Purpose For patients treated with partial breast irradiation (PBI), potential long-term treatment-related toxicities are important. The 1.5 T magnetic resonance guided linear accelerator (MRL) offers excellent tumor bed visualization and a daily treatment plan adaption possibility, but MRL-specific electron stream and return effects may cause increased dose deposition at air–tissue interfaces. In this study, we aimed to investigate the projected risk of radiation-induced secondary malignancies (RISM) in patients treated with PBI at the 1.5 T MRL. Methods Projected excess absolute risk values (EARs) for the contralateral breast, lungs, thyroid and esophagus were estimated for 11 patients treated with PBI at the MRL and compared to 11 patients treated with PBI and 11 patients treated with whole breast irradiation (WBI) at the conventional linac (CTL). All patients received 40.05 Gy in 15 fractions. For patients treated at the CTL, additional dose due to daily cone beam computed tomography (CBCT) was simulated. The t‑test with Bonferroni correction was used for comparison. Results The highest projected risk for a radiation-induced secondary cancer was found for the ipsilateral lung, without significant differences between the groups. A lower contralateral breast EAR was found for MRL-PBI (EAR = 0.89) compared to CTL-PBI (EAR = 1.41, p = 0.01), whereas a lower thyroid EAR for CTL-PBI (EAR = 0.17) compared to MRL-PBI (EAR = 0.33, p = 0.03) and CTL-WBI (EAR = 0.46, p = 0.002) was observed. Nevertheless, when adding the CBCT dose no difference between thyroid EAR for CTL-PBI compared to MRL-PBI was detected. Conclusion Better breast tissue visualization and the possibility for daily plan adaption make PBI at the 1.5 T MRL particularly attractive. Our simulations suggest that this treatment can be performed without additional projected risk of RISM.

Failure is a common experience in the lives of musicians and educators that is frequently seen as a negative attribute for performances in music education. By shifting from a negative, destructive approach to a positive, constructive orientation to failure, music educators can help their students learn and advance forward from experiences of failure toward success. This approach requires the creation of a classroom environment that allows failure to be accepted and transparent and focuses on a growth mindset regarding student success and failure. This article presents instructional strategies that model and support the growth of effective practices for coping with failure socially, emotionally, and cognitively.

Background We recently published 2-year results of the prospective, randomized IMRT-MC2 trial, showing non-inferior local control and cosmesis in breast cancer patients after conventionally fractionated intensity-modulated radiotherapy with simultaneously integrated boost (IMRT-SIB), compared to 3D-conformal radiotherapy with sequential boost (3D-CRT-seqB). Here, we report on 2-year quality of life results. Patients and Methods 502 patients were enrolled and randomized to IMRT-SIB (50.4 Gy in 1.8 Gy fractions with a 64.4 Gy SIB to the tumor bed) or to 3D-CRT-seqB (50.4 Gy in 1.8 Gy fractions, followed by a sequential boost of 16 Gy in 2 Gy fractions). For quality of life (QoL) assessment, patients completed the QLQ-C30 and QLQ-BR23 questionnaires at baseline, 6 weeks and 2 years after radiotherapy. Results Significant differences between treatment arms were seen 6 weeks after radiotherapy for pain (22.3 points for IMRT vs. 27.0 points for 3D-CRT-seqB; p = 0.033) and arm symptoms (18.1 points for IMRT vs. 23.6 points for 3D-CRT-seqB; p = 0.013), both favoring IMRT-SIB. Compared to baseline values, both arms showed significant improvement in global score (IMRT: p = 0.009; 3D-CRT: p = 0.001) after 2 years, with slight deterioration on the role (IMRT: p = 0.008; 3-D-CRT: p = 0.001) and social functioning (IMRT: p = 0.013, 3D-CRT: p = 0.001) as well as the future perspectives scale (IMRT: p = 0.003; 3D-CRT: p = 0.0034). Conclusion This is the first randomized phase III trial demonstrating that IMRT-SIB was associated with slightly superior QoL compared to 3-D-CRT-seqB. These findings further support the clinical implementation of SIB in adjuvant breast cancer treatment.

Highlights • The electron-stream effect is responsible of an out-of-field dose when performing partial breast irradiation at the MR-linac. • The electron-stream effect is located to the patient́s chin and, for lateral targets, to the arm. • The electron-stream effect is effectively minimized by a bolus. • Novel concepts and clinical trials for breast cancer at the 1.5 T MR-linac can be tested., Introduction The hybrid magnetic resonance linear accelerator (MRL) has the potential to test novel concepts in breast cancer patients such as daily MR-guided real-time plan adaptation. Before starting clinical trials, preparatory studies for example of the MR-dependent electron stream effect (ESE) are necessary. Material and Methods To prospectively investigate the ESE, data from 11 patients treated with partial breast irradiation (PBI) at the 1.5 T MRL were evaluated. A bolus was placed on the chin and in vivo dosimetry results were compared with the dose simulated by the treatment planning system (TPS). The same measurements were carried out for three patients treated at a conventional linac. Toxicity and cosmesis were evaluated. Results Median doses measured and simulated on top/ underneath the bolus were 1.91 / 0.62 Gy and 2.82 / 0.63 Gy, respectively. Median differences between calculations and measurements were 0.8 Gy and 0.1 Gy. At the conventional linac, median measured doses on top/ underneath the bolus were 0.98 and 1.37 Gy. No acute toxicity exceeding grade 2 was recorded. Cosmesis was good or excellent and patient reported outcome measures were mostly scored as none or mild. Conclusion The dose due to the ESE is low, correctly predicted by the TPS and effectively minimized by a bolus.

Purpose Hypofractionated radiotherapy is the standard of care for adjuvant whole breast radiotherapy (RT). However, adoption has been slow. The indication for regional nodal irradiation has been expanded to include patients with 0–3 involved lymph nodes. We investigated the impact of the publication of the updated German S3 guidelines in 2017 on adoption of hypofractionation and enrollment of patients with lymph node involvement within a randomized controlled phase III trial. Methods In the experimental arm of the HYPOSIB trial (NCT02474641), hypofractionated RT with simultaneous integrated boost (SIB) was used. In the standard arm, RT could be given as hypofractionated RT with sequential boost (HFseq), normofractionated RT with sequential boost (NFseq), or normofractionated RT with SIB (NFSIB). The cutoff date for the updated German S3 guidelines was December 17, 2017. Temporal trends were analyzed by generalized linear regression models. Multiple logistic regression models were used to investigate the influence of time (prior to/after guideline) and setting (university hospital/other institutions) on the fractionation patterns. Results Enrollment of patients with involved lymph nodes was low throughout the trial. Adoption of HFseq increased over time and when using the guideline publication date as cutoff. Results of the multiple logistic regressions showed an interaction between time and setting. Furthermore, the use of HFseq was significantly more common in university hospitals. Conclusion The use of HFseq in the standard arm increased over the course of the HYPOSIB trial and after publication of the S3 guideline update. This was primarily driven by patients treated in university hospitals. Enrolment of patients with lymph node involvement was low throughout the trial.

Cancer-related fatigue (CRF) is a common side effect of cancer treatment, particularly in breast cancer patients. Over the past decade, the multimodal management of breast cancer has undergone several changes, such as the establishment of postoperative hypofractionated radiotherapy (RT) as a new standard protocol and the reduced use of chemotherapy. The aim of the current study was to investigate the impact of these changes on quality of life (QoL) and CRF. A total of 66 patients was assessed for QoL and CRF using the FACIT‑F questionnaire. Patients were asked to complete the paper-based questionnaire before (TP1) and at the end of radiotherapy (TP2) as well as at follow-up (TP3). Subgroups were compared based on fractionation and previous application of chemotherapy. For the entire cohort, no significant changes in the severity of fatigue were seen. A mild decrease of physical wellbeing (PWB) from TP1 to TP2 was observed (22.2 vs. 20.7, p = 0.007). Fatigue at TP1 was more severe in patients receiving chemotherapy before RT (37.9 vs. 30.5, p = 0.041). Only patients without preceding chemotherapy showed a significant worsening of fatigue from TP1 to TP2 (37.9 vs 34.8, p = 0.005). The same is true for physical wellbeing (PWB), with a decrease from TP1 to TP2 in chemotherapy-naive patients only (23.5 vs. 21.4, p = 0.002). Fractionation did not impact any of the investigated endpoints. Patients undergoing postoperative RT for breast cancer constitute a heterogeneous patient population with varying risks of developing CRF influenced by previous treatments. Therefore, patient selection seems to be critical when interventional studies addressing CRF during radiotherapy are designed.

This quasi-experimental study investigated the transfer of learning for effective practice strategies from large ensemble to individual rehearsal. Five middle school bands were randomly assigned to one of three conditions. Two treatment conditions had teachers use an iterative, explicit instruction protocol to teach a targeted practice strategy during a sight-reading activity on a novel piece of music over a series of six lessons. The control condition included non-specific sight-reading activities. A sample of students from each band (N=66) participated in a cycle of pre-test/post-test/delay-test observations that involved a ten- minute practice session followed by a performance on a new piece of music similar to those used in the treatment sessions. Student practice sessions were analyzed for frequency of usage of the targeted strategies, and performances were rated for pitch and rhythmic accuracy. A 3x2x3 ANOVA identified a significant effect for strategy used within groups (F(1,63)=122.388, p

Introduction External beam partial breast irradiation (PBI) provides equal oncological outcomes compared to whole breast irradiation when applied to patients with low risk tumours. Recently, linacs with an integrated magnetic resonance image-guidance system have become clinically available. Here we report the first-in-human PBI performed at the 1.5 T MR-Linac, with a focus on clinical feasibility and investigation of the air electron stream effect (ESE) and the electron return effect (ERE) in the presence of the 1.5 T magnetic field, which might influence the dose on the chin (out-of-field dose, due to the ESE), the skin and the lung/chest wall interface (in-field dose, ERE). Methods A 59 years old patient affected by a 15 mm unifocal grade 1 carcinoma not special type of the right breast staged pT1c pN0 cM0 was planned and treated at Unity 1.5 T MR-Linac. To investigate the ERE and the ESE, an MR-Linac treatment plan was simulated without considering the 1.5 T B field using a research version of Monaco (V. 5.19.03). In vivo dosimetry was performed using Gafchromic® EBT3 films placed on top and underneath a 1 cm bolus which was placed on the patient’s chin. The plans with and without 1.5 T magnetic field were compared in terms of dose to the chin, to the skin and to the interface lung/chest wall. Finally, the dose on the chin measured with the in vivo dosimetry was compared with the dose calculated by Monaco. Results PBI using the 1.5 T MR-Linac was successfully performed with a 7 MV photon 7-beams IMRT step-and-shoot plan. The treatment was well tolerated, the patient developed a slight acute toxicity, i.e. breast skin erythema and breast oedema CTC V.4 grade 1. The plan with 1.5 T magnetic field documented a fractional dose of 0.17 Gy in the chin area (2.6 Gy in 15 fractions), which was reduced to 0.05 Gy (0.75 in 15 fractions) by the presence of 1 cm bolus. The simulated plan without magnetic field showed a dose reduced by 2.3 Gy in the chin area. With the in vivo dosimetry a fractional dose of, respectively, 0.12 Gy and 0.034 Gy on top and underneath the bolus were measured (1.8 and 0.51 Gy in 15 fractions). The plan with 1.5 T magnetic field showed a skin D2 of 40 Gy and a skin V35 of 40.2%, which were reduced to, respectively, 39.7 Gy and 24.9% in the simulation without magnetic field. At the interface lung/chest there were no differences in DVH statistics. Conclusion PBI with the 1.5 T MR-Linac was performed for the first time. ESE is accurately calculated by the treatment planning system, can be effectively reduced with a 1 cm bolus and is comparable to dose of cone beam-CT based position verification. The additional dose caused by ERE is not associated with an increased risk of acute toxicity.

Defined as the ability to engage in music activities on one’s own, musical independence is a frequent goal of music education. This yearlong study investigated musical independence within concert bands through interviews and observations of participants of secondary programs that included musical independence as a primary objective. Constructivist grounded theory analyses of the participants’ experiences led to a model of musical independence that included three interrelated outcomes: student agency, critical decision making, and lifewide/lifelong musicianship. These outcomes were the result of specific instructional practices that utilized cognitive modeling, scaffolded instruction, and authentic, regular, student-led music-making in curricular ensembles to promote student agency and decision making. These instructional practices relied upon preconditions for independence, including musical, social, and 21st-century skills foundations frequently found in large-ensemble classrooms. This study provides a model that can be situated within current large-ensemble practices to support the development of musical independence.

This retrospective analysis aimed to address the efficacy of total nodal irradiation (TNI)-based reconditioning regimens in pediatric patients with graft failure/rejection after allogeneic hematopoietic cell transplantation.Thirty-three pediatric patients with malignant (n = 25) and nonmalignant diseases (n = 8) were treated with a TNI-based reconditioning regimen. All patients received a 7-Gy single dose combined with anti-T lymphocyte antibody OKT3 (n = 16), anti-thymocyte globulin (n = 24), fludarabine (n = 31), and/or thiotepa (n = 28), followed by an infusion of peripheral blood stem cells (n = 31) or bone marrow transplant (n = 2). Twenty-eight of 33 patients had haploidentical family donors.After a median of 11 days, engraftment was seen in 32 of 33 children. Two children died 34 days after retransplantation because of either disease relapse or treatment-related multiple organ failure. Severe acute toxicity was reported in only 1 child (systemic inflammatory response syndrome-like reaction; recovery after cortisone treatment). The average follow-up was 60.2 months (range, 1.1-162.5 months). Event-free and overall survival rates at 2/5 years follow-up were 62.0%/58.6% and 65.1%/61.7%, respectively. Despite sustained engraftment, 12 patients died from disease relapse (n = 3), Moschkowitz syndrome (n = 1), or multiple organ failure (n = 8). Follow-up data were available for 18 of 21 survivors, with a median follow-up of 92.8 months (range, 3.6-162.5 months). Hypothyroidism was present in 78.6% of patients, and sex/growth hormonal insufficiencies were reported for 37.5%. Mean forced expiratory volume in 1 second after TNI was 84%; mean vital capacity was 79%. Severe growth failure (3rd percentile) occurred in 28.6% (height) and 35.7% (weight) of patients. No secondary malignancies were reported.In the high-risk group of patients with graft failure/rejection after allogeneic hematopoietic cell transplantation, the TNI-based reconditioning regimen seems to allow sustained engraftment combined with a favorable toxicity profile, leading to long-term event-free and overall survival. Late toxicity after a median follow-up of over 7.5 years includes growth failure, manageable hormonal deficiencies, and a low risk of decrease of lung function.

Purpose This retrospective analysis aims to address the toxicity and efficacy of a modified total nodal irradiation (TNI)-based conditioning regimen before haploidentical hematopoietic cell transplantation (HCT) in pediatric patients. Materials and methods Patient data including long-term follow-up were evaluated of 7 pediatric patients with malignant (n = 2) and non-malignant diseases (n = 5) who were treated by a primary TNI-based conditioning regimen. TNI was performed using anterior/posterior opposing fields. All patients received 7 Gy single-dose TNI combined with systemic agents followed by an infusion of peripheral blood stem cells (n = 7). All children had haploidentical family donors. Results Engraftment was reached in 6/7 children after a median time of 9.5 days; 1 child had primary graft failure but was successfully reconditioned shortly thereafter. After an average follow-up time of 103.5 months (range 8.8–138.5 months), event-free (EFS) and overall survival (OS) rates were 71.4% and 85.7%, respectively. One child with a non-malignant disease died 8.8 months after transplantation due to a relapse and a multiple organ failure. Follow-up data was available for 5/6 long-term survivors with a median follow-up (FU) of 106.2 months (range 54.5–138.5 months). Hypothyroidism and deficiency of sexual hormones was present in 3/5 patients each. Mean forced expiratory volume in 1 s (FEV1) after TNI was 71%; mean vital capacity (VC) was 78%. Growth failure ( Conclusion In this group of patients, a primary single-dose 7 Gy TNI-based conditioning regimen before HCT in pediatric patients allowed sustained engraftment combined with a tolerable toxicity profile leading to long-term OS/EFS. Late toxicity after a median FU of over 9 years includes growth failure, manageable hormonal deficiencies, and acceptable decrease in lung function.

Purpose In the modern era, improvements in radiation therapy techniques have paved the way for simultaneous integrated boost irradiation in adjuvant breast radiation therapy after breast conservation surgery. Nevertheless, randomized trials supporting the noninferiority of this treatment to historical standards of care approach are lacking. Methods A prospective, multicenter, randomized phase 3 trial (NCT01322854) was performed to analyze noninferiority of conventional fractionated intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB) to 3-D conformal radiation therapy with sequential boost (3-D-CRT-seqB) for breast cancer patients. Primary outcomes were local control (LC) rates at 2 and 5 years (noninferiority margin at hazard ratio [HR] of 3.5) as well as cosmetic results 6 weeks and 2 years after radiation therapy (evaluated via photo documentation calculating the relative breast retraction assessment [pBRA] score [noninferiority margin of 1.25]). Results A total of 502 patients were randomly assigned from 2011 to 2015. After a median follow-up of 5.1 years, the 2-year LC for the IMRT-SIB arm was noninferior to the 3-D-CRT-seqB arm (99.6% vs 99.6%, respectively; HR, 0.602; 95% CI, 0.123-2.452; P = .487). In addition, noninferiority was also shown for cosmesis after IMRT-SIB and 3-D-CRT-seqB at both 6 weeks (median pBRA, 9.1% vs 9.1%) and 2 years (median pBRA, 10.4% vs 9.8%) after radiation therapy (95% CI, –0.317 to 0.107 %; P = .332). Cosmetic assessment according to the Harvard scale by both the patient and the treating physician as well as late-toxicity evaluation with the late effects normal tissues- subjective, objective, management, analytic criteria, a score for the evaluation of long-term adverse effects in normal tissue, revealed no significant differences between treatment arms. In addition, there was no difference in overall survival rates (99.6% vs 99.6%; HR, 3.281; 95% CI: –0.748 to 22.585; P = .148) for IMRT-SIB and 3-D-CRT-seqB, respectively. Conclusions To our knowledge, this is the first prospective trial reporting the noninferiority of IMRT-SIB versus 3-D-CRT-seqB with respect to cosmesis and LC at 2 years of follow-up. This treatment regimen considerably shortens adjuvant radiation therapy times without compromising clinical outcomes.

Background: 10-year results from several studies showed improved disease-free survival and distant metastasis-free survival, reduced breast cancer-related mortality, and variable effects on overall survival with the addition of partial or comprehensive regional lymph node irradiation after surgery in patients with breast cancer. We present the scheduled 15-year analysis of the European Organisation for Research and Treatment of Cancer (EORTC) 22922/10925 trial, which aims to investigate the impact on overall survival of elective internal mammary and medial supraclavicular (IM-MS) irradiation. Methods: EORTC 22922/10925, a randomised, phase 3 trial done across 46 radiation oncology departments from 13 countries, included women up to 75 years of age with unilateral, histologically confirmed, stage I–III breast adenocarcinoma with involved axillary nodes or a central or medially located primary tumour. Surgery consisted of mastectomy or breast-conserving surgery and axillary staging. Patients were randomly assigned (1:1) centrally using minimisation to receive IM-MS irradiation at 50 Gy in 25 fractions (IM-MS irradiation group) or no IM-MS irradiation (control group). Stratification was done for institution, menopausal status, site of the primary tumour within the breast, type of breast and axillary surgery, and pathological T and N stage. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival analysed according to the intention-to-treat principle. Secondary endpoints were disease-free survival, distant metastasis-free survival, breast cancer mortality, any breast cancer recurrence, and cause of death. Follow-up is ongoing for 20 years after randomisation. This study is registered with ClinicalTrials.gov, NCT00002851. Findings: Between Aug 5, 1996, and Jan 13, 2004, we enrolled 4004 patients, of whom 2002 were randomly assigned to the IM-MS irradiation group and 2002 to the no IM-MS irradiation group. At a median follow-up of 15·7 years (IQR 14·0–17·6), 554 (27·7%) patients in the IM-MS irradiation group and 569 (28·4%) patients in the control group had died. Overall survival was 73·1% (95% CI 71·0–75·2) in the IM-MS irradiation group and 70·9% (68·6–72·9) in the control group (HR 0·95 [95% CI 0·84–1·06], p=0·36). Any breast cancer recurrence (24·5% [95% CI 22·5–26·6] vs 27·1% [25·1–29·2]; HR 0·87 [95% CI 0·77–0·98], p=0·024) and breast cancer mortality (16·0% [14·3–17·7] vs 19·8% [18·0–21·7]; 0·81 [0·70–0·94], p=0·0055) were lower in the IM-MS irradiation group than in the control group. No significant differences in the IM-MS irradiation group versus the control group were seen for disease-free survival (60·8% [95% CI 58·4–63·2] vs 59·9% [57·5–62·2]; HR 0·93 [95% CI 0·84–1·03], p=0·18), or distant metastasis-free survival (70·0% [67·7–72·2] vs 68·2% [65·9–70·3]; 0·93 [0·83–1·04], p=0·18). Causes of death between groups were similar. Interpretation: The 15-year results show a significant reduction of breast cancer mortality and any breast cancer recurrence by IM-MS irradiation in stage I–III breast cancer. However, this is not converted to improved overall survival. Funding: US National Cancer Institute, Ligue Nationale contre le Cancer, and KWF Kankerbestrijding.

Musical independence is a common objective for large-ensemble classes, but traditional, teacher-centric instructional practices for these groups may discourage rather than promote students’ critical thinking and decision making in music. Cognitive apprenticeship provides an instructional approach through which student musicians can develop skills for musical independence, including critical thinking and problem solving, while at the same time maintaining high-quality large ensembles. This process involves three stages of instruction: modeling, coaching, and fading. This article presents examples from several band directors who use a cognitive apprenticeship approach that can be applied to all types of large ensembles to help students develop the skills and competencies needed to engage with music meaningfully on their own, both within and outside the music classroom.

Background: Pathological complete response (pCR) is accepted by FDA as a surrogate endpoint for accelerated approval of targeted agents in combination with chemotherapy based on better long-term outcomes compared to residual disease (Cortazar 2014). Methods: The multi-center, adaptively-randomized I-SPY2 platform trial uses pCR as the primary endpoint to identify investigational agents that will improve outcomes in women with stage 2/3 breast cancer with high risk of early recurrence, across all signatures, based on hormone receptor (HR), HER2, and 70-gene (MammaPrint) status. For patients with HR+ HER2- tumors, only 70-gene (Mammaprint) high-risk patients are enrolled. To date, 1200+ patients have been randomized to one of 14 arms: control (paclitaxel followed by AC); veliparib/carboplatin; neratinib; MK2206; trebananib; trastuzumab/pertuzumab; ado-trastuzumab emtansine/pertuzumab; pembrolizumabx4; ganitumab/metformin; ganetespib; PLX-3397. 7 agents graduated in at least one signature (> 85% probability of success in a 300-patient phase III confirmatory trial); 2 did not graduate; 1 stopped for toxicity, and 3 are enrolling (patritumab/trastuzumab, talazoparib/irinotecan, pembrolizumabx8). Local pathologists were centrally trained using the Residual Cancer Burden (RCB) assessment to ensure uniform evaluation and response classification; RCB 0 = pCR. Results: We evaluated the relationship between pCR and event free (EFS) and distant disease free survival (DDFS) in the first 522 pts (median follow-up:2.5 years). 180 pts achieved pCR (36%) while 338 did not (RCB=1-3). There were 82 EFS and 65 DRFS events. Over the entire group (including all arms), pCR was highly associated with 3-year EFS (p 3-year survival (pCR group)Hazard Ratio OverallOverallHR+/HER2-HER2+TNBCEFS97%0.08 (0.03-0.23)0.14 (0.02-1.04)0 (NA)0.11 (0.03-0.37)DDFS98%0.08 (0.03-0.26)0.17 (0.01-1.23)0 (NA)0.09 (0.02-0.40) Conclusions: The first long-term efficacy results from the I-SPY2 TRIAL demonstrate that achieving pCR is a very strong surrogate endpoint for improved EFS and DDFS in a high-risk population, across all treatment arms, regardless of subtype. I-SPY2 shows substantially lower estimated EFS hazards for patients achieving pCR, compared to the 5 yr EFS hazard ratio for pCR vs not in Cortazar (hazard ratio 0.49), demonstrating important differences between a metaanalysis compared to a platform trial with uniform high-risk eligibility, standardized pathology assessment, and multiple targeted therapies. Our data support the use of pCR as a primary endpoint for accelerated approval of new drugs if EFS is evaluated in the same population. Based on these findings, the I-SPY2 TRIAL will test whether therapy can be deescalated or escalated for individual patients with the goal of achieving pCR for all. Citation Format: Yee D, DeMichele A, Isaacs C, Symmans F, Yau C, Albain KS, Hylton NM, Forero-Torres A, van't Veer LJ, Perlmutter J, Rugo HS, Melisko M, Chen Y-Y, Balassanian R, Krings G, Datnow B, Hasteh F, Tipps A, Weidner N, Zhang H, Tickman R, Thornton S, Ritter J, Amin K, Klein M, Chen B, Keeney G, Ocal T, Feldman M, Klipfel N, Sattar H, Mueller J, Gwin K, Baker G, Kallakury B, Zeck J, Duan X, Ersahin C, Gamez R, Troxell M, Mansoor A, Grasso LeBeau L, Sams S, Wisell J, Wei S, Harada S, Vinh T, Stamatakos MD, Tawfik O, Fan F, Adams A, Rendi M, Minton S, Magliocco A, Sahoo S, Fang Y, Hirst G, Singhrao R, Asare SM, Wallace AM, Chien AJ, Ellis ED, Han HS, Clark AS, Boughey JC, Elias AD, Nanda R, Korde L, Murthy R, Lang J, Northfelt D, Khan Q, Edmiston KK, Viscusi R, Haley B, Kemmer K, Zelnak A, Berry DA, Esserman LJ. Pathological complete response predicts event-free and distant disease-free survival in the I-SPY2 TRIAL [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS3-08.

Purpose/Objective(s) We recently published 2-year results of the prospective, randomized IMRT-MC2 trial, showing non-inferior local control and cosmesis in breast cancer patients after conventionally fractionated intensity-modulated radiotherapy with simultaneously integrated boost (IMRT-SIB), compared to 3D-conformal radiotherapy with sequential boost (3D-CRT-seqB). The present study reports on 2-year quality of life results. Materials/Methods Five hundred two patients were enrolled to analyze non-inferiority of IMRT-SIB (50.4 Gy in 1.8 Gy fractions with a 64.4 Gy SIB to the tumor bed in 2.3 Gy fractions) to 3D-CRT-seqB (50.4 Gy in 1.8 Gy fractions, followed by a sequential boost of 16 Gy in 2 Gy fractions). For quality of life (QoL) assessment, patients completed the QLQ-C30 (15 items) and QLQ-BR23 (8 items) questionnaires at baseline and 6 weeks and 2 years after radiotherapy. Comparisons between treatment groups were made at 6 weeks and 2 years after radiotherapy, using Mann-Whitney U-test. The Friedmann test was used to compare QoL at different time points during follow-up (baseline, 6 weeks and 2 years after radiotherapy) and to detect significant changes of QoL over all time points. Results After six weeks and two years, 237 and 212 QoL questionnaires (94 % and 84 %) were available in the IMRT group, 231 and 210 (93 % and 84 %) in the control group, respectively. The only significant difference of QoL scores between the IMRT-SIB and the 3-D-CRT-seqB group was seen 6 weeks after radiotherapy for pain (22.3 points for IMRT vs. 27.0 points for 3D-CRT-seqB; P = 0.033; r = 0.102) and for arm symptoms (18.1 points for IMRT vs. 23.6 points for 3D-CRT-seqB; P = 0.013; r = 0.118), both favoring IMRT. Looking at changes after two years compared to baseline, both arms showed significant improvement in global score (IMRT: P = 0.009, r = 0.021; 3D-CRT: P = 0.001, r = 0.028) with slight deterioration on the role (IMRT: P = 0.008, r = 0.021; 3-D-CRT: P = 0.001, r = 0.038) and social functioning (IMRT: P = 0.013, r = 0.021; 3D-CRT: P = 0.001, r = 0.033) as well as the future perspectives scale (IMRT: P = 0.003, r = 0.026; 3D-CRT: P = 0.0034, r = 0.020). Conclusion This is the first randomized phase III trial demonstrating that simultaneously integrated boost irradiation was associated with slightly superior quality of life compared to conventional sequential boost irradiation. These findings further support the widely clinical implementation of SIB in adjuvant breast cancer treatment. NCT01322854

Teacher licensure policies and state standards for English/language arts have made content area literacy a necessary component for most music teacher education programs. Unlike teachers in other areas of the school curriculum, music educators have not broadly integrated literacy into their instructional practices. The Before-During-After (B-D-A) instructional framework is commonly used in content area literacy and provides a powerful tool for promoting student critical thinking and metacognitive awareness. B-D-A is supported by content area literacy strategies that can be used across the curriculum, and music educators can use them to encourage student engagement with authentic music texts by focusing on the artistic processes of responding and connecting. Adoption of content area literacy and B-D-A into music ensemble methods coursework can aid preservice and in-service music teachers as they engage students in music learning, support cross-curricular collaboration and professional development, and promote overall student literacy.

Background and purpose Outcome of patients with genitourinary rhabdomyosarcoma has been improved in the past, but organ preservation rates are too low. Conservative surgery with LDR-brachytherapy has been advocated, but LDR-brachytherapy is often not available. We wanted to establish a novel treatment modality combining HDR-brachytherapy and conservative surgery. Material and Methods We performed an organ preserving tumor resection with intraoperative placement of brachytherapy tubes. Suitable patients were selected following assessment of response to neoadjuvant chemotherapy where organ preserving surgical resection was deemed feasible. In bladder-prostate rhabdomyosarcoma, only tumors located below the bladder neck could be treated by brachytherapy. After surgery, high dose rate brachytherapy was carried out for 30–36Gy total dose. Results A total of 11 patients were treated up to now (embryonal histology n =10, alveolar histology n =1) with a median follow-up of 18months [4–80]. All patients were IRS group III. There were no significant side effects. One patient had local relapse and was successfully treated with re-excision. All other patients are in the first complete remission. One patient developed a neurogenic bladder and required creation of a Mitrofanoff stoma. Conclusion Combined conservative surgery and high dose rate brachytherapy is a treatment option for selected rhabdomyosarcoma patients. The paper highlights the essential technical challenges and clearly shows limitations of this treatment approach.

To prospectively investigate the role of re-irradiation (re-RT) combined with hyperthermia (HT) in a contemporary cohort of patients affected by recurrent breast cancer (RBC). Within the prospective registry HT03, patients with resected RBC and previous irradiation were included. Re-RT was applied to the recurrence region with doses of 50–50.4 Gy, with a boost up to 60–60.4 Gy to the microscopically or macroscopically positive resection margins (R1/R2) region. Concurrent HT was performed at 40–42 ℃. Primary endpoint was LC. Acute and late toxicity, overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) were also evaluated. 20 patients and 21 RBC were analyzed. Median re-RT dose was 50.4 Gy and a median of 11 HT fractions were applied. Re-RT+HT was well tolerated, with three patients who experienced a grade (G) 3 acute skin toxicity and no cases of ≥G3 late toxicity. With a median follow up of 24.7 months, two local relapses occurred. Ten patients experienced regional and/or distant disease progression. Five patients died, four of them from breast cancer. PFS was favorable in patients treated with re-RT+HT for the first recurrence with doses of 60 Gy. A trend towards better CSS was found in patients with negative or close margins and after doses of 60 Gy. Full-dose re-RT+HT for RBC is well tolerated, provides good LC, and seems to be more effective when applied at the time of the first relapse and after doses of 60 Gy. The registry will be continued for validation in a larger cohort and with longer follow-up.

The causes of degenerative disease of the upper and lower motor neurons are incompletely understood. In this review the current concepts in the clinical and genetic differential diagnostics of motor neuron diseases are presented. Hereditary spastic paraplegia, primary lateral sclerosis, spinal muscular atrophy and amyotrophic lateral sclerosis are explained, structured according to the affection of the upper and/or lower motor neuron. The substantial variability in the presentation and course of motor neuron diseases as well as the lack of specific laboratory tests hinder an early diagnosis. The precise description of the clinical picture, thorough testing of possible differential diagnoses as well as monitoring of the clinical course are essential. Genetic analyses should be offered to patients with a positive family history. Early identification of clinical and genetic subentities of the individual motor neuron diseases is a prerequisite for future neuroprotective interventions.

Degenerative stenotic spondylosis is not an uncommon cause of cervical spondylotic myelopathy (CSM) and cauda equina lesions in the aged population. Limited standardization exists with respect to diagnostic and therapeutic procedures.Literature review with respect to diagnostic and therapeutic procedures for neurologically relevant cervical and lumbar spinals stenosis.Comprehensive literature review.Clinical neurological examination and diagnostic imaging are fundamental for the diagnosis of neurologically relevant cervical and lumbar spinal stenosis. Additional laboratory blood and cerebrospinal fluid testing might be required for a differential diagnosis. Neurophysiological testing is reserved for specific clinical problems. The clinical evidence for the efficacy of conservative therapeutic strategies is limited.

This qualitative case study describes how a band director, whose objectives included the development of musical independence, designed his classroom, curriculum, and instruction and how his students experienced this pedagogical practice. Teachers and students of a secondary-level concert band were observed and interviewed over the course of an 8-week concert cycle. The lead teacher utilized a constructivist approach comprised of three interrelated elements: a deliberately structured band environment, teacher-moderated instruction, and student-led engagement. The teacher-moderated and student-led elements were situated within an educational space that emphasized musical rigor, social engagement, and extramusical skills. This environment promoted students’ musical growth with support from social and extramusical resources. The teacher facilitated learning through scaffolded instruction that included modeling, guided problem solving and decision-making, and intentional vagueness. These strategies invited students to actively engage in critical thinking and take personal responsibility within the large ensemble setting. Students applied their learning from teacher-moderated instruction to student-led music opportunities in both large and chamber ensembles. The teacher monitored but did not participate in student-led activities, allowing the students to make their own musical diagnoses and decisions. He used his observations to determine specific student needs and inform his own instructional practice. Students demonstrated musical independence to varying degrees as the teacher facilitated learning differently dependent on student, content, and situation.

Background Low blood 25-hydroxyvitamin D (25(OH)D) concentrations have been associated with cancer in dogs. Little research has examined what other factors may affect 25(OH)D concentrations. Objectives (1) To determine whether the presence of cancer (lymphoma, osteosarcoma, or mast cell tumor [MCT]) in dogs is associated with plasma 25(OH)D concentrations and (2) identify other factors related to plasma 25(OH)D concentrations in dogs. Animals Dogs newly diagnosed with osteosarcoma (n = 21), lymphoma (n = 27), and MCT (n = 21) presented to a tertiary referral oncology center, and healthy, client-owned dogs (n = 23). Methods An observational study design was used. Dietary vitamin D intake, sex, age, body condition score (BCS), muscle condition score (MCS), and plasma concentrations of 25(OH)D, 24,25-dihydroxyvitamin D (24,25(OH)2D) (a marker of CYP24A1 activity), as well as ionized calcium (ICa), parathyroid hormone, and parathyroid hormone-related protein concentrations were measured. An analysis of covariance was used to model plasma 25(OH)D concentrations. Results Cancer type (P = 0.004), plasma 24,25(OH)2D concentrations (P < 0.001), and plasma ICa concentrations (P = 0.047) had significant effects on plasma 25(OH)D concentrations. Effects of age, sex, body weight, BCS, MCS, and plasma PTH concentrations were not identified. A significant interaction between ICa and cancer was found (P = 0.005). Plasma 25(OH)D concentrations increased as ICa concentrations increased in dogs with cancer, whereas plasma 25(OH)D concentrations decreased as ICa concentrations increased in healthy dogs. Conclusions and Clinical Importance Results support a relationship between cancer and altered vitamin D metabolism in dogs, mediated by plasma ICa concentrations. The CYP24A1 activity and plasma ICa should be measured in studies examining plasma 25(OH)D concentrations in dogs.

Der Anteil der extranodalen Non-Hodgkin-Lymphome (NHL) an der Gesamtheit der NHL betragt ca. 30%. Haufigste Lokalisationen sind Haut (v. a. T-Zell-NHL), Magen, Dunndarm, Tonsille und ZNS (v. a. B-Zell-NHL). Seltenere Lokalisationen der extranodalen NHL sind Augenhohle, Speicheldrusen, Nase, Nasennebenhohlen, Schilddruse, Lunge, Blase, Brustdruse, weiblicher Genitaltrakt, Hoden, Knochen und extradural. Fur die Therapie der extranodalen NHL sind Stadium, Lokalisation und Histologie entscheidend. Da extranodale NHL im Gegensatz zu nodalen NHL haufiger in den Stadien I/II diagnostiziert werden, kommt der Radiotherapie (RT) eine hohe Bedeutung zu. Bei niedrig malignen Lymphomen wird i. Allg. eine alleinige Involved-Field-Radiotherapie (IF-RT) mit einer Dosis von 30–40 Gy empfohlen. Aufgrund einer hohen lokalen Kontrolle und Verhinderung einer systemischen Erkrankung werden hohe krankheitsfreie Uberlebensraten und Gesamtuberlebensraten erreicht. Bei aggressiver Histologie hingegen wird prinzipiell eine Induktionschemotherapie vor konsolidierender IF-RT (Dosis 36–40 Gy) durchgefuhrt. Lokale Kontrolle, krankheitsfreies Uberleben und Gesamtuberleben unterscheiden sich nach Lokalisation und vorliegender Histologie erheblich.

Enteral feeding via gastric tube has become part of routine care for critically ill patients. However, studies investigating the optimal volume and duration of nutrition in these patients are lacking. Moreover, underestimation of residual gastric volume due to gastric emptying disorders provides increased pulmonary aspiration risk. In this context, gastric ultrasonography allows qualitative and quantitative assessment of gastric contents and volume in nonobese and obese patients using an ultrasound based measurement of the cross-sectional area (CSA) of the antrum.

Ultrasound measurement of the optic nerve sheath diameter (ONSD) has been utilized as an indirect assessment of intracranial pressure (ICP). Currently, the normal ONSD is believed to be < 5 mm, whereas diameters above 6 mm are considered to reflect a clinically significant increase in ICP. Despite these standard values, the ONSD has never been compared with simultaneously measured ICP values in awake, spontaneously breathing patients.

Die postoperative Strahlentherapie des Endometriumkarzinoms erfolgt risikoadaptiert. Auf der Basis chirurgisch ermittelter Tumorausdehnung und histophatologischer Kriterien erfolgt die Identifikation von Tumoren mit erhohtem lokoregionarem Rezidivrisiko. Fur die postoperative Strahlentherapie stehen die intravaginale Brachytherapie und/oder die externe Hochvoltbestrahlung als adjuvante Therapiemasnahmen zur Verfugung. Die primare, alleinige Strahlentherapie wird heute nur bei inoperablen Tumoren oder bei erhohten pulmonalen und/oder kardialen Risiken durchgefuhrt, da durch die Operation und adjuvante Bestrahlung gunstigere Heilungsraten zu erzielen sind. Mit der modernen dreidimensionalen Bestrahlungsplanung (mittels CT/MRT) wird eine prazise Erfassung des Zielvolumens bei gleichzeitig subtiler Schonung der Risikostrukturen gewahrleistet.

A young white man with new-onset central diabetes insipidus was discovered to have a posterior pituitary mass on magnetic resonance imaging. No other radiological abnormalities were noted in the anterior pituitary, infundibulum or hypothalamus. No other endocrinopathies were present: laboratory investigations showed normal basal concentrations of anterior pituitary hormones, including prolactin. The patient was suspected to have sarcoidosis affecting the posterior pituitary, because of the discovery of pulmonary sarcoidosis during his diagnostic evaluation. His symptoms of polydipsia and polyuria responded promptly to intranasal administration of 1-desamino-8-D-arginine vasopressin (DDAVP). The patient demonstrated complete regression of the posterior pituitary mass after a course of corticosteroid therapy. However, his diabetes insipidus persisted and he continues to need DDAVP treatment, currently at 12 months of follow-up. The resolution of the neurohypophysial mass was compatible with the diagnosis of pituitary sarcoidosis and this precluded the need for a transsphenoidal biopsy or surgery.

Objective To investigate the relationship between the detection of prostatic intra-epithelial neoplasia (PIN) on initial prostate biopsy and subsequent invasive prostatic adenocarcinoma. Patients and methods Thirty-six men (mean age 67 years, range 52–82) with PIN underwent digital rectal examination (DRE), serum prostate-specific antigen (PSA) measurement and transrectal ultrasonography (TRUS) before the initial biopsy and documentation of PIN. They were followed up with serial PSA, TRUS and a repeat biopsy every 6 months until either invasive carcinoma was identified or 2 years had elapsed. Results The initial biopsy revealed Grade I PIN in 33%, Grade II in 22%, and Grade III in 45% of the men. The repeat biopsy showed evidence of invasive carcinoma in 21 patients (58%; Group I), while 15 (42%) showed persistence of PIN (Group II). In Group I, 19 had had high-grade PIN (Grade II/III) on initial biopsy compared with one in Group II. The findings on DRE, and age, were not significantly different between groups. TRUS revealed a hypoechoic lesion in 15/21 patients in Group I compared with 7/15 patients in Group II. There was an increase in PSA level in 18 patients in Group I (from 8.4 to 11.6 ng/mL). Conclusions PIN and invasive adenocarcinoma of the prostate were closely associated, and the likelihood for coexistence was higher in patients with high-grade PIN, increasing PSA level or positive findings on TRUS. We recommend that all patients who show high-grade PIN on prostate biopsy be followed very closely with serial PSA measurements and repeat biopsies from both the area of PIN and other areas of the prostate.

The aim of this retrospective study was to analyze the outcome of patients with locally advanced cervical carcinoma treated by adjuvant radiochemotherapy and to determine risk factors for local and distant relapse. Furthermore, acute and late effects of treatment were recorded. A total of 72 patients with FIGO stages I–III cervical carcinoma were treated by radical hysterectomy, pelvic lymphadenectomy, and postoperative radiochemotherapy. Only patients with positive pelvic lymph nodes, parametrial involvement, positive margins, or tumor bulk were eligible. Patients were irradiated with a standard pelvic field (50.4 Gy in 28 fractions). The majority of patients received platinum-based chemotherapy. After a median follow-up of 37 months, estimated 1-, 2-, and 4-year disease-free survival (DFS) and overall survival (OS) rates were 89%, 80%, 68% and 95%, 88%, 76%, respectively. Nine of the 72 patients had pelvic recurrences including only 1 isolated local failure; 23 of the 72 patients presented with distant relapse. The majority of relapses occurred within the first 3 years after adjuvant treatment. The number of positive pelvic lymph nodes (> 1) was the strongest prognostic factor for DFS. Treatment was well tolerated with transient acute hematologic (~30%) and gastrointestinal (~30%) grade 3 toxicity. Small bowel obstruction (~6%) was the only important late sequelae. Adjuvant radiochemotherapy in patients with advanced cervical cancer and several risk factors is highly effective to prevent local relapse. Future efforts to improve outcome should be placed on improvement of systemic control especially in subgroups with high-risk features for distant relapse. Combined treatment was well tolerated with moderate acute and late toxicity.

The mammographic and histologic findings were reviewed in 41 consecutive cases of isolated lobular carcinoma in situ (LCIS) unassociated with any malignant diagnosis. Thirty-one needle-directed breast biopsies were performed to evaluate clustered microcalcifications. In 24 of the 31 cases, the calcifications were found in areas of benign breast disease, with LCIS representing a separate process. In the few cases in which microcalcifications were seen in association with LCIS, a greater number of similar calcifications were present in adjacent benign disease. Soft-tissue abnormalities necessitating the performance of a biopsy represented benign foci, except in one patient with LCIS in and adjacent to a fibroadenoma. The authors conclude that LCIS has no characteristic mammographic features. LCIS is detected as an incidental finding at breast biopsy, with the mammographic abnormality predominantly reflecting a benign process.