Evaluation of dose, volume, and outcome in children with localized, intracranial ependymoma treated with proton therapy within the prospective KiProReg Study

BACKGROUND: Radiotherapy (RT) of ependymoma in children is an important part of the interdisciplinary treatment concept. However, feasibility and dose concepts are still under investigation, particularly in very young children. The aim of this study was to evaluate the standard dose and volume of proton therapy (PT) in children with ependymoma. METHODS: In this analysis, 105 patients with localized, intracranial ependymoma under the age of 18 years treated with PT between 2013 and 2018 were included. Patient characteristics, treatment, outcome, and follow-up data were analyzed using descriptive statistics, Kaplan-Meier, and Cox regression analysis. RESULTS: The median age of patients at PT was 2.8 years (0.9-17.0 years). The molecular subgroup analysis was performed in a subset of 50 patients (37 EP-PFA, 2 EP-PFB, 7 EP-RELA, 2 EP-YAP, 2 NEC [not elsewhere classified]). The median total dose was 59.4 Gy (54.0-62.0 Gy). The median follow-up time was 1.9 years. The estimated 3-year overall survival (OS), local control (LC), and progression-free survival (PFS) rates were 93.7%, 74.1%, and 55.6%, respectively. Within univariable analysis, female gender and lower dose had a positive impact on OS, whereas age ≥4 years had a negative impact on OS and PT given after progression had a negative impact on PFS. In the multivariable analysis, multiple tumor surgeries were associated with lower PFS. New ≥3° late toxicities occurred in 11 patients. CONCLUSION: For children with localized ependymoma, PT was effective and well tolerable. Multiple surgeries showed a negative impact on PFS

Medical Students’ Development of Ethical Judgment – Exploring the Learners’ Perspectives using a mixed methods approach

Objective: Contemporary healthcare requires physicians to have well developed ethical judgment skills in addition to excellent clinical skills. However, no consensus has been reached on how to best teach ethical judgment skills during medical training. Previous studies revealed inconclusive results and applied varying theoretical frameworks. To date, the students’ perspectives on their development in ethical judgment has received less attention. Better insights in the learners’ experiences can help to improve educational interventions in medical ethics.Methods: A vignette featuring a challenging case with opposing views between a patient’s parents and a physician followed by a questionnaire was presented to a cohort of medical students at a German medical school at three points in time during their medical training (Year 1, 2 and 5). The questionnaire included closed and open-ended questions addressing the participant’s preferred, hypothetical actions, their reasoning as well as the resources informing their reasoning. Content analysis was used for qualitative data; frequencies and percentages were used to describe quantitative findings. Results: The response rate remained stable (28%) over the study period. Participants’ responses changed overtime. Accepting parents’ autonomy in the decision-making process was the majority standpoint of students in year 1 and 2 and became less often cited in year 5 (Year 1/2/5: 68/67/48%). On the contrary, not readily following the parents’ decision for medical reasons was a minority standpoint in year 1 and became more prevalent over time (year 1/2/5: 12/17/42%). Judgments were only partly based on ethics training. Instead, participants drew on experiences from their clinical clerkships and their personal lives. Throughout the study, participants did not feel well-prepared to make a judgment in the case (Average 2.7 on a Likert-Scale; 1=very well prepared, 4=very poor). Conclusions: Over the course of their medical training, the participants seemed to increasingly frame the presented vignette as a medical problem. To optimize the development of ethical judgment teaching of ethics should be more integrated in clinical teaching. In addition to the analysis of rare and extreme cases, teaching ethics should also expand on challenges students and junior doctors commonly encounter themselves to promote ethical sensitivity and confidence in students

Medical Students’ Development of Ethical Judgment – Exploring the Learners’ Perspectives using a mixed methods approach

Objective: Contemporary healthcare requires physicians to have well developed ethical judgment skills in addition to excellent clinical skills. However, no consensus has been reached on how to best teach ethical judgment skills during medical training. Previous studies revealed inconclusive results and applied varying theoretical frameworks. To date, the students’ perspectives on their development in ethical judgment has received less attention. Better insights in the learners’ experiences can help to improve educational interventions in medical ethics. Methods: A vignette featuring a challenging case with opposing views between a patient’s parents and a physician followed by a questionnaire was presented to a cohort of medical students at a German medical school at three points in time during their medical training (Year 1, 2 and 5). The questionnaire included closed and open-ended questions addressing the participant’s preferred, hypothetical actions, their reasoning as well as the resources informing their reasoning. Content analysis was used for qualitative data; frequencies and percentages were used to describe quantitative findings. Results: The response rate remained stable (28%) over the study period. Participants’ responses changed overtime. Accepting parents’ autonomy in the decision-making process was the majority standpoint of students in year 1 and 2 and became less often cited in year 5 (Year 1/2/5: 68/67/48%). On the contrary, not readily following the parents’ decision for medical reasons was a minority standpoint in year 1 and became more prevalent over time (year 1/2/5: 12/17/42%). Judgments were only partly based on ethics training. Instead, participants drew on experiences from their clinical clerkships and their personal lives. Throughout the study, participants did not feel well-prepared to make a judgment in the case (Average 2.7 on a Likert-Scale; 1=very well prepared, 4=very poor). Conclusions: Over the course of their medical training, the participants seemed to increasingly frame the presented vignette as a medical problem. To optimize the development of ethical judgment teaching of ethics should be more integrated in clinical teaching. In addition to the analysis of rare and extreme cases, teaching ethics should also expand on challenges students and junior doctors commonly encounter themselves to promote ethical sensitivity and confidence in students

Comparison of adverse events in partial- or whole breast radiotherapy: investigation of cosmesis, toxicities and quality of life in a meta-analysis of randomized trials

Abstract Purpose/objective Adjuvant whole breast radiotherapy and systemic therapy are part of the current evidence-based treatment protocols for early breast cancer, after breast-conserving surgery. Numerous randomized trials have investigated the therapeutic effects of partial breast irradiation (PBI) compared to whole breast irradiation (WBI), limiting the treated breast tissue. These trials were designed to achieve equal control of the disease with possible reduction in adverse events, improvements in cosmesis and quality of life (QoL). In this meta-analysis, we aimed to investigate the differences between PBI and WBI in side effects and QoL. Material/methods We performed a systematic literature review searching for randomized trials comparing WBI and PBI in early-stage breast cancer with publication dates after 2009. The meta-analysis was performed using the published event rates and the effect-sizes for available acute and late adverse events. Additionally, we evaluated cosmetic outcomes as well as general and breast-specific QoL using the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Results Sixteen studies were identified (n = 19,085 patients). PBI was associated with a lower prevalence in any grade 1 + acute toxicity and grade 2 + skin toxicity (OR = 0.12; 95% CI 0.09–0.18; p < 0.001); (OR = 0.16; 95% CI 0.07–0.41; p < 0.001). There was neither a significant difference in late adverse events between the two treatments, nor in any unfavorable cosmetic outcomes, rated by either medical professionals or patients. PBI-technique using EBRT with twice-daily fractionation schedules resulted in worse cosmesis rated by patients (n = 3215; OR = 2.08; 95% CI 1.22–3.54; p = 0.007) compared to WBI. Maximum once-daily EBRT schedules (n = 2071; OR = 0.60; 95% CI 0.45–0.79; p < 0.001) and IORT (p = 0.042) resulted in better cosmetic results grade by medical professionals. Functional- and symptom-based QoL in the C30-scale was not different between PBI and WBI. Breast-specific QoL was superior after PBI in the subdomains of “systemic therapy side effects” as well as “breast-” and “arm symptoms”. Conclusion The analysis of multiple randomized trials demonstrate a superiority of PBI in acute toxicity as well breast-specific quality of life, when compared with WBI. Overall, late toxicities and cosmetic results were similar. PBI-technique with a fractionation of twice-daily schedules resulted in worse cosmesis rated by patients

Long-term follow-up of children with neuroblastoma receiving radiotherapy to metastatic lesions within the German Neuroblastoma Trials NB97 and NB 2004

Purpose Neuroblastoma (NB) is the most common extracranial solid malignancy during childhood. Despite a multimodal treatment approach, the prognosis of patients with metastatic NB is not satisfactory. Although radiotherapy (RT) has become an integral part of treatment of the primary tumor, the role of RT in osteomedullary lesions is not well defined. A retrospective analysis was conducted to evaluate the impact of RT for metastatic sites in children with high-risk NB. Methods All patients with stage 4 NB from the prospective, multicenter NB trials NB97 and NB2004 who received RT to metastatic sites during frontline treatment were included in this retrospective analysis. Results A total of 18 children were irradiated with a median dose of 36 Gray (Gy; range 20-45 Gy) to one or more (range 1-3) osteomedullary metastases with or without concomitant RT to the primary tumor site. The median follow-up time was 149 months (range 55-220) in survivors. At 5 years, local relapse-free survival (LRFS) at irradiated metastatic sites and metastases-free survival (MFS) at distant, non-irradiated site rates were 51.4 and 39.9%, respectively. The estimated overall survival (OS) rate at 5 years was 49.4%. No high-grade acute or late toxicity and no secondary malignancy was reported. Conclusion RT to metastases is feasible for patients with stage 4 NB. However, an impact of RT to residual metastatic sites on outcome was not found. Studies with larger cohorts or prospective trials would be desirable in order to elucidate the role of RT for metastases

Post-Neoadjuvant Treatment Strategies in Breast Cancer

Neoadjuvant chemotherapy enables close monitoring of tumor response in patients with breast cancer. Being able to assess tumor response during treatment provides an opportunity to evaluate new therapeutic strategies. Thus, for triple-negative breast tumors, it was demonstrated that additional immunotherapy could improve prognosis compared with chemotherapy alone. Furthermore, adjuvant therapy can be escalated or de-escalated correspondingly. The CREATE-X trial randomly assigned HER2-negative patients with residual tumor after neoadjuvant therapy to either observation or capecitabine. In HER2-negative patients with positive BRCA testing, the OlympiA study randomly assigned patients to either observation or olaparib. HER2-positive patients without pathologic remission were randomly assigned to trastuzumab or trastuzumab&ndash;emtansine within the KATHERINE study. These studies were all able to show an improvement in oncologic outcome associated with the escalation of therapy in patients presenting with residual tumor after neoadjuvant treatment. On the other hand, this individualization of therapy may also offer the possibility to de-escalate treatment, and thereby reduce morbidity. Among WSG-ADAPT HER2+/HR-, HER2-positive patients achieved comparable results without chemotherapy after complete remission following neoadjuvant treatment. In summary, the concept of post-neoadjuvant therapy constitutes a great opportunity for individualized cancer treatment, potentially improving outcome. In this review, the most important trials of post-neoadjuvant therapy are compiled and discussed

Early Outcome, Cosmetic Result and Tolerability of an IOERT-Boost Prior to Adjuvant Whole-Breast Irradiation

Background/Aims: Due to its favorable dose distribution and targeting of the region at highest risk of recurrence due to direct visualization of tumor bed, intraoperative electron radiation therapy (IOERT) is used as part of a breast-conserving treatment approach. The aim of this study was to analyze tumor control and survival, as well as the toxicity profile, and cosmetic outcomes in patients irradiated with an IOERT boost for breast cancer. Materials and Methods: 139 Patients treated at our institution between January 2010 and January 2015 with a single boost dose of 10 Gy to the tumor bed during breast-conserving surgery followed by whole-breast irradiation were retrospectively analyzed. Results: 139 patients were included in this analysis. The median age was 54 years (range 28&ndash;83 years). The preferred surgical strategy was segmental resection with sentinel lymphonodectomy (66.5%) or axillary dissection (23.1%). Regarding adjuvant radiotherapy, the vast majority received 5 &times; 1.8 Gy to 50.4 Gy. At a median follow-up of 33.6 months, recurrence-free and overall survival were 95.5% and 94.9%, respectively. No patient developed an in-field recurrence. Seven patients (5.0%) died during the follow-up period, including two patients due to disease recurrence (non-in-field). High-grade (CTCAE &gt; 2) perioperative adverse events attributable to IOERT included wound healing disorder (N = 1) and hematoma (N = 1). High-grade late adverse events (LENT-SOMA grade III) were reported only in one patient with fat necrosis. Low-grade late adverse events (LENT-SOMA grade I-II) included pain (18.0%), edema (10.5%), fibrosis (21%), telangiectasia (4.5%) and pigmentation change (23.0%). The mean breast retraction assessment score was 1.66 (0&ndash;6). Both patients and specialists rated the cosmetic result &ldquo;excellent/good&rdquo; in 84.8% and 87.9%, respectively. Conclusion: Our study reports favorable data on the cosmetic outcome as well as the acute and early long-term tolerability for patients treated with an IOERT boost. Our oncologic control rates are comparable to the previous literature. However, prospective investigations on the role of IOERT in comparison to other boost procedures would be desirable