Technical Considerations on Proton Therapy in NRG's Multi-Institutional Clinical Trials.

Recommendations for radiation treatment in pediatric patients with metastatic rhabdomyosarcoma: Expert consensus from the International Soft Tissue SaRcoma ConsorTium (INSTRuCT).

Deformable Dose Mapping and Accumulation Techniques for Stereotactic Body Radiation Therapy (SBRT) of Lung Cancers.

A real-world analysis of the impact of azole antifungal prophylaxis on outcomes in patients with newly diagnosed acute myeloid leukemia treated with venetoclax-based therapy.

Objective: To investigate the surgical safety and oncological efficacy of minimally invasive surgery (MIS) for primary gastric gastrointestinal stromal tumors (GISTs) with a maximum diameter of ≤5 cm. Methods: A retrospective cohort study was conducted. The inclusion criteria were as follows: patients undergoing radical local resection via MIS, pathologically confirmed primary gastric GISTs, maximum tumor diameter ≤5 cm, and complete available clinicopathological data, adjuvant therapy information and follow-up records. The exclusion criteria included multiple GISTs, a history of other malignant tumors, and distant metastasis or local invasion detected preoperatively or intraoperatively. Clinical data of 517 patients with gastric GISTs who underwent radical surgery at Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2018 to December 2024 were retrospectively collected. All patients were divided into four groups according to surgical approaches: laparoscopic surgery group (Lap group, n=411), robotic surgery group (Robot group, n=9), endoscopic surgery group (Endo group, n=44), and laparoscopic-endoscopic cooperative surgery group (LECS group, n=53). Partial gastrectomy was performed in the Lap, Robot and LECS groups, while endoscopic submucosal dissection was the only surgical method in the Endo group. The Lap group was further subdivided into the favorable anatomical location subgroup (Lap-F group, e.g., anterior wall, greater curvature) and the unfavorable anatomical location subgroup (Lap-C group, e.g., posterior wall, lesser curvature, cardia, pylorus) based on tumor location. The LECS group was divided into the laparoscopy-dominated resection subgroup (LECS-L group) and the endoscopy-dominated resection subgroup (LECS-E group) according to the resection modality. Perioperative outcomes and follow-up data of patients in different groups were observed and analyzed. Results: Among all the patients, 227(43.9%) were male , with a median age of 62.5 (55.0, 68.0) years. There were 105 cases with tumor diameter ≤2.0 cm and 412 cases with 2.1-5.0 cm. According to postoperative pathological risk stratification, 98 cases were very low-risk, 368 low-risk, 36 moderate-risk and 15 high-risk. Baseline data comparison showed no statistically significant differences in gender, age and mitotic count among the Lap, Robot, Endo and LECS groups (all P>0.05), while significant differences were found in tumor growth direction, tumor diameter and pathological risk grade (all P<0.001). No statistically significant baseline differences were observed between the Lap-F and Lap-C groups, nor between the LECS-L and LECS-E groups (all P>0.05). All surgeries were successfully completed in the four groups. R0 resection was achieved in all patients of the Lap, Robot and LECS groups, while the surgical margin could not be evaluated in the Endo group. The average operation time of the four groups was (91.4±40.8) minutes, (104.8±28.8) minutes, (60.2±40.5) minutes and (141.7±19.4) minutes, the numbers of patients with intraoperative blood loss ≤50 ml in each group were 356, 7, 44, and 46, respectively. The median time to resuming liquid diet was 4.0 (3.0,4.0) days, 4.0 (3.0,6.0) days, 3.0 (2.0,3.0) days and 4.0 (4.0,5.0) days, and the median postoperative hospital stay was 6.0 (5.0,7.0) days, 6.0 (5.0,8.5) days, 4.0 (4.0,6.0) days and 7.0 (5.0,8.0) days in the four groups, respectively. Intraoperative complications occurred in 13 cases of the Lap group (all with intraoperative bleeding, blood loss >200 ml), 1 case of intraoperative perforation in the Endo group, 1 case of intraoperative bleeding in the LECS group, and no intraoperative complications in the Robot group. Postoperative complications were observed in 17 cases of the Lap group, including 5 cases of gastroparesis, 10 cases of pulmonary infection, 1 case of pancreatic fistula and 1 case of incision bleeding; no relevant postoperative complications were found in the other three groups. Subgroup analysis revealed that the operation time in the Lap-F group was significantly shorter than that in the Lap-C group [(79.3±39.0) minutes vs. (98.1±40.4) minutes, t=-4.566, P<0.001], with no statistically significant differences in other intraoperative and postoperative outcomes (all P>0.05). No statistically significant differences were found in all intraoperative and postoperative indicators between the LECS-L and LECS-E groups (all P>0.05). The median follow-up duration of all patients was 34 (19, 53) months, and no tumor recurrence, metastasis or death was observed in any patient during the follow-up period. Conclusion: Laparoscopic surgery, robotic laparoscopic surgery, endoscopic surgery and laparoscopic-endoscopic cooperative surgery all yield excellent surgical safety and oncological efficacy in the treatment of gastric GISTs with a maximum diameter of ≤5 cm. Tumor anatomical location has a certain impact on the operation time of laparoscopic surgery, but no significant effect on surgical safety and efficacy. In laparoscopic- endoscopic cooperative surgery, both endoscopy-dominated and laparoscopy-dominated tumor resection achieve comparable surgical safety and therapeutic efficacy.

With the development of critical care techniques, continuous renal replacement therapy (CRRT) has become one of the most important life support methods. It is a key procedure to select and apply prescribed fluids for CRRT correctly, which is helpful to guarantee the performance and effect of CRRT and avoid some adverse complications. Critical Care Medicine Branch of China International Exchange and Promotion Association for Medical and Health Care and the Chinese Cooperation Group of Critical Care Blood Purification (CCG-CCBP) have developed this guideline to improve the CRRT level of related medical personnel, promote the standardization of CRRT, and improve the prognosis of those patients who receive CRRT. This guideline addresses five aspects: common types and components of CRRT prescription solutions, solute loss and replenishment in CRRT, clinical use of CRRT prescription solutions, adjustments to CRRT prescription solutions in special circumstances, and local citrate anticoagulation. It raises 17 clinical questions and uses the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) grading method to assess the quality of evidence and the strength of recommendations, ultimately resulting in 22 recommendations.

Ewing sarcoma (ES) is a bone and soft tissue sarcoma that is absolutely dependent on the EWS::FLI1 transcription factor for cell survival. No compound has been shown to reverse EWS::FLI1 activity in patients, and outcomes for relapsed patients remain poor. Trabectedin above a threshold concentration reverses the activity of EWS::FLI1 and is potentiated by low-dose irinotecan in vivo. This open-label phase 1/2 trial of trabectedin with irinotecan (SARC037) enrolled 37 relapsed/refractory patients with ES. The primary objectives were to determine the safety, tolerability, recommended phase 2 dose (RP2D; phase 1) and objective response rate (ORR; phase 2) of trabectedin administered as a 1-hour infusion in combination with low-dose irinotecan in patients with ES. The secondary objectives were to determine the progression-free survival (PFS), 6-month PFS, duration of response and 18F-fluorothymidine positron emission tomography (18F-FLT PET) avidity of ES tumors. The RP2D was trabectedin 1.0 mg m-2 over 1 hour (day 1) and irinotecan 25 mg m-2 (days 2 and 4) of a 21-day cycle. Toxicities were manageable with grade 3 or higher toxicities (>15%) of myelosuppression and alanine aminotransferase elevations at RP2D. The phase 2 ORR was 33% (39%, including RP2D phase 1 patients), and 6-month PFS was 48%. Transcriptional profiling demonstrated reversal of the EWS::FLI1 transcriptome in tumors from a subset of patients. Additional correlative objectives captured molecular profiling, circulating tumor DNA levels, pharmacokinetics and 18F-FLT PET avidity. Here we provide the basis for further development of trabectedin/irinotecan for patients with ES by the international cooperative groups. ClinicalTrials.gov: NCT04067115 .

Abstract Background Prostate-specific membrane antigen (PSMA) PET/CT has transformed prostate cancer (PCa) management by improving lesion detection and guiding treatment decisions across disease stages. Following the first paper of the Italian PSMA Survey focused on technical aspects and primary staging, this second analysis explores its clinical use in PSA persistence after radical prostatectomy, biochemical recurrence (BCR), hormone-sensitive metastatic (mHSPC), and castration-resistant metastatic (mCRPC) settings. Methods A national cross-sectional survey was conducted jointly by five Italian scientific societies involving nuclear medicine physicians, medical oncologists, radiation oncologists, and urologists (AIMN, AIOM, AIRO, SIU, SIUrO) and the Meet-URO cooperative group. Dedicated sections addressed the adoption, timing, and perceived clinical impact of PSMA PET/CT in PSA persistence after radical prostatectomy, BCR, mHSPC, and mCRPC. Responses were analysed descriptively and stratified by medical competences (clinicians versus nuclear medicine physicians). Results PSMA PET/CT emerged as the preferred imaging modality in all clinical scenarios. In PSA persistence and BCR, 87–95% of respondents selected PSMA PET as first-line imaging, most often performed at PSA levels of 0.2–0.5 ng/mL. When negative, more than two-thirds recommended repeating PSMA PET/CT after PSA further rise. In mHSPC, over 80% of clinicians applied the CHAARTED criteria directly to PSMA PET findings, while PSMA PET/CT was also widely used for restaging and therapy monitoring. In mCRPC, PSMA PET/CT was routinely used for baseline and follow-up imaging. Most clinicians considered the low-dose CT component sufficient for radioligand therapy (RLT) eligibility, while [ 18 F]Fluorodeoxyglucose (FDG) PET was reserved for selected high-risk or discordant cases. Conclusion PSMA PET/CT has become the central imaging modality in the management of advanced PCa in Italy. Its adoption has progressed faster than supporting evidence, underscoring the need for prospective validation, implementation of harmonised interpretation criteria, and unified national recommendations.

Phase II trials are intended to identify promising treatment paradigms for definitive phase III testing, but how effectively they serve this role in radiation oncology is unknown. We evaluated whether phase II cooperative group studies of radiation therapy function as effective gateways to phase III testing and identified factors associated with downstream progression. Using ClinicalTrials.gov, we identified completed phase II radiation therapy trials conducted through the National Clinical Trials Network cooperative groups. We assessed whether trials met their prespecified primary end point and whether successful trials progressed to phase III evaluation. Logistic regression evaluated associations between trial characteristics and phase III transition. Decision concordance between phase II outcomes and subsequent development decisions was examined. Among 92 completed phase II trials (2003-2019), 54% met their primary end point, yet only 17% progressed to phase III testing. Among trials that met their end point, fewer than one third advanced, with 71% representing discordant successes (positive phase II trial without phase III progression). Toxicity-based end points most frequently met phase II criteria (67%) but were least likely to translate to phase III (8% of successful trials). Larger enrollment number (odds ratio [OR], 1.68 per 50 patients [95% CI, 1.21 to 2.31]) and longer duration (OR, 1.20 per year [95% CI, 1.00 to 1.44]) were associated with phase III transition. Trials that advanced to phase III were not completed more rapidly (median duration 132 v 108 months). Most phase II radiation oncology trials that meet prespecified end points do not progress to definitive phase III testing. This phenomenon appears driven less by statistical futility than by structural and decisional barriers. Greater prespecification of advancement intent and selection of decision-relevant end points may improve the efficiency and impact of radiotherapy cooperative group trials.

This study determined the impacts of cooperative learning instruction in the social skill development of Grade I pupils. This employed 10 Grade I pupils in selected schools in Matnog I District, Matnog Sorsogon. Using descriptive method of research, the researcher discovered that the teachers utilized different cooperative learning approaches in developing the social behavior of grade I pupils which are peer- interactive cooperative tasks (group work activities), partner-based (pairing of pupils, dyad, buddy system); team-based (collaborative learning teams), technology-enhanced collaboration (digital peer engagement), cooperative learning approaches game-based group learning, and discussion-based Collaboration (dialogue). The study also found out that that these cooperative learning activities are effective in developing the social skills of the learners. The teachers develop the social skills of learners through various activities including using real-world situations that the children oftentimes encounter, giving merit to group or each member, choosing deliberately activities that promote self-confidence lo lessen pupils’ shyness, and providing support and structure during class activities. However, challenges are experienced in developing the social skills of the learners through cooperative learning. These challenges include some pupils tend to remain socially withdrawn, time constraints in preparing collaborative activities, limited learning resources necessary for adoption of cooperative learning strategies, and some pupils exhibit resistance to collaborative tasks. Based on these findings, the researcher recommended the use of different approaches in developing their social skills of the pupils, strategies to encourage the participation of pupils in developing the social skills. The researcher likewise recommends to empower teachers on the use of cooperative learning activities in developing the social skills of pupils through LAC sessions.

Background Self-regulation of learning is a key consideration in the process of acquiring workplace competences. One key assumption of self-regulated learning in the literature is that the learner themself is undertaking a process of learning. However, in adult and vocational educational settings it is common that tasks may be either individual or cooperative. Theoretically, self-regulatory demands are different when applied to different learning forms, such as an individual task vs a cooperative learning task; but to date there is a dearth of empirical studies in this regard. Method Part of the CADCoM2024 + study on measuring CAD and FEM competences at EQF 6, the present study was conducted with 175 students from four mechanical engineering technical colleges in Germany. Through quantitative analysis we compared progression in CAD and FEM competency development in two learning approaches: individual self-regulated learning vs cooperative self-regulated learning. Results Strict invariance was partially present in both cross-sectional and longitudinal analyses. The differences in mean values suggest that there was strong learning progression in both individual self-regulated learning and cooperative self-regulated learning treatment groups. Interestingly, progression in FEM competency was better through cooperative self-regulated learning; however, progression in CAD competency was better through individual self-regulated learning. This latter finding was surprising given that students had demonstrated that they could work well together cooperatively, as shown in the FEM learning tasks. Conclusion This original interdisciplinary study suggests that skills for both individual and cooperative self-regulated learning are important for optimally acquiring workplace competences. Indeed, an important finding from this original study was that both individual and cooperative self-regulated learning are recommended as learning strategies: students made strong progress in competency development in both learning forms. Whether individual self-regulated learning or cooperative self-regulated learning is chosen as a pedagogical strategy for fostering workplace competences may depend on a variety of factors (such as interest, previous experience, social environment, and nature of the task). Further studies, including studies with larger sample sizes, are required to unpick this complexity and to confirm which factors might influence the pedagogical choice between individual and cooperative self-regulated learning strategies for competency development.

Concurrent and complex aerial missions with multiple targets exceed the capabilities of a single cooperative formation of high-speed flight vehicles (HSFVs). To address this challenge, this article decomposes a fleet of HSFVs (subject to multiple compounding factors, including unknown aerodynamic disturbances, unmodeled or parametric uncertainties, actuator faults, and potential intervehicle collisions) into several subgroups and develops a recurrent neural network (RNN) online learning-based prescribed-time safe and robust cooperative group formation control protocol under dynamic event-triggered communication. A distributed prescribed-time event-triggered estimator (DP-TE-TE) is first developed to drive all HSFVs to acquire the convex hull information (i.e., input, velocity, and position) spanned by multiple virtual leader vehicles (VLVs) before grouping or the input, velocity, and position information of their respective single VLV within the group after grouping. Then, based on the constraint-following theory, the safety distance inequality between any potentially colliding pair of HSFVs, along with the first-order differential equation involving the formation position tracking error, is converted into collision motion constraints and prescribed-time trajectory tracking constraints, respectively. To enhance the flight control performance of the swarm, an RNN is constructed for each HSFV to learn the unknown nonlinear function induced by multiple compounding factors, thereby providing online compensation for the subsequent control design. Finally, by integrating the constraint-following errors derived from collision motion constraints and prescribed-time trajectory tracking constraints, the RNN compensation term, and the estimated information, the prescribed-time safe and robust cooperative group formation control scheme (P-TSRCGFCS) is proposed. In the simulation examples, the effectiveness of the proposed algorithms is verified by dividing 12 HSFVs and three VLVs into three subgroups to perform the desired cooperative group formation task.

Childhood cancer outcomes in low- and middle-income countries (LMICs), where over 80% of the world's children reside, remain drastically lower than in high-income countries (HICs). This vast disparity stems from pervasive challenges, including limited healthcare access, inadequate resources, delayed diagnosis, and differences in disease biology influenced by varied genetic ancestries. The direct translation of intensive HIC protocols often results in elevated treatment-related mortality (TRM) in resource-constrained settings, highlighting the critical need for locally validated regimens. Current barriers to establishing robust research capacity include minimal research training, overwhelmed specialists, excessive and misaligned ethical/regulatory oversight-even for low-risk studies-and pharmaceutical industry strategies that favor trials in HICs. To bridge this survival gap, a paradigm shift is required, moving from protocol translation to context-specific clinical research. This strategy must prioritize Implementation and Comparative Effectiveness studies to validate adapted treatments. Key initiatives must include local genomic characterization for equitable risk allocation and an innovative "repurposing" of novel agents by adjusting dosages and schedules to enhance feasibility and reduce toxicity within local supportive care capacity. Strengthening international cooperative research groups and fostering a multi-stakeholder dialogue among regulators, industry, and civil society are essential to expedite the generation of robust, locally relevant evidence that can inform public health policy and ensure every child has access to the best chance of cure at their local site.

Electronic data capture (EDC) has the potential to improve trial data accuracy and efficiency. The Children's Oncology Group Pediatric Early Phase Clinical Trials Network (PEP-CTN) and Pediatric Brain Tumor Consortium (PBTC) conducted a joint pilot that aimed to assess feasibility of automated transfer of laboratory data from electronic health records to the Medidata Rave EDC (Rave). Second, we compared data from automated extraction (EXTRACTED) and manual ascertainment (MANUAL) during the original studies using two representative tests, bilirubin and platelet count (PLT). Data from 78 patients treated on seven completed PBTC or PEP-CTN trials at seven hospitals were included. Each consortium created a Rave instance to receive data. Sites elected to use local methods or the ExtractEHR R package. Postextraction data were uploaded to the Rave Batch Uploader (BU)-associated file transfer protocol client and BU uploaded data into Rave. After successful upload, discrepancies between EXTRACTED and MANUAL data were categorized. All sites successfully extracted required laboratory data and had 1+ complete upload. PBTC/PEP-CTN operational effort and close collaboration with hospital site technical teams was required. Owing to study closure timing, only two sites checked EXTRACTED data from their first patient list; this identified incomplete mapping that was fixed before second patient list extraction. Beyond incomplete mapping, discrepancies for bilirubin and PLT were commonly due to mismatched values or units (Consortium 1 PLT: 3/10 (30%); Consortium 2 PLT: 152/176 (86%)). This study demonstrated that automated laboratory data ascertainment is feasible in pediatric cooperative oncology group trials. Although this required up-front central operational and local site-based effort, lessons learned from this pilot can inform future studies using automated data capture.

Cooperation in public goods is expected to evolve more rapidly in smaller groups than in larger groups because individuals receive a larger share of the benefits, reducing the benefits of freeloading. However, experimental evidence for this hypothesis remains limited to microorganisms, restricting our understanding of the evolution of cooperative traits. Here, we show that in the collectively defending larvae of Neodiprion sertifer, survival against predation is higher in cooperative groups, with benefits of cooperation more pronounced in small groups (5 larvae) than in large groups (20 larvae). Individuals also participate less in collective defence in larger groups, not because of higher life-history costs resulting from increased resource competition but because they adjust their contribution according to group size. These results provide novel empirical evidence that selection for cooperation in collective goods is group size-dependent, promoting cooperation in smaller groups, whereas the relative fitness of freeloaders is higher in larger groups.

This article presents some results related to an ongoing research project aimed at adapting and incorporating into an educational social network some of the teaching tools and didactic strategies proposed by the Cooperating to Learn / Learning to Cooperate Program. The goal is to teach students to learn in cooperative groups from an inclusive perspective. The study follows a qualitative approach based on a multiple case study methodology. Its purpose is to analyze and interpret how this innovative didactic proposal helps teachers in implementing cooperative teaching and learning processes in virtual environments mediated by digital instructional tools. The research focuses on four upper primary school classes. The selected schools represent different levels of experience in the use of cooperative learning techniques and digital technologies. The results presented here address one of the specific objectives of the study: to evaluate the implementation of cooperative structures adapted to the virtual environment in order to guide learning in cooperative groups. The findings provide evidence of the impact of the proposal on increasing students’ motivation and interest, fostering equitable participation, simultaneous interaction, and mutual support, as well as improving teacher’s professional competence, from the perspective of both students and teachers.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has long constituted a cornerstone of post-remission consolidation therapy for adults with high-risk B-cell acute lymphoblastic leukemia (B-ALL), offering potent graft-versus-leukemia activity at the expense of significant treatment-related toxicity (TRT) and non-relapse mortality (NRM). Over the past two decades, however, outcomes following allo-HSCT have improved substantially. This progress has been driven primarily by a marked reduction in NRM, translating into improved overall survival (OS), as consistently documented by large cooperative group analyses and single-center series. Advances in supportive care, infectious prophylaxis, donor selection, and graft-versus-host disease (GvHD) prevention have contributed substantially to this improvement. In parallel, transplant decision-making has been profoundly reshaped by refined disease biology-based risk stratification and the systematic evaluation of measurable residual disease (MRD). Moreover, the advent of highly effective immunotherapeutic approaches-including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor (CAR) T-cell therapies-has enabled the achievement of deeper molecular remissions prior to transplantation, both in first and subsequent complete remissions. Taken together, these developments have shifted allo-HSCT from a widely applied strategy to a more individualized, risk-adapted therapeutic approach. This review examines how the indications, timing, and objectives of allo-HSCT are evolving in the contemporary treatment landscape of adult B-ALL, with particular emphasis on Philadelphia chromosome-negative, Philadelphia-like, and Philadelphia chromosome-positive disease subsets.

“Ready-to-eat” is defined as the status of the food being ready for immediate consumption. For some ready-toeat foods, legal microbiological criteria exist, and in addition different national guidelines are available to complement&#13;\nlegally enforceable standards. Control charts are used to statistically study results of a manufacturing process over a&#13;\nperiod of time with the aim to demonstrate if the process is under control. The current research examined the&#13;\nmicrobiological quality of 177 ready-to-eat food samples in the catering cooperative group “La Cascina,” in Latium,&#13;\nItaly, during a period of one year (2014–2015). Contamination trends were reported as individual control charts that&#13;\nwere used to identify out-of-control data, address appropriate corrective actions, and finally promote quality&#13;\nimprovements by setting customized dynamic control limits. Meals were individually analyzed using the alternative Micro&#13;\nBiological Survey method, in parallel with the conventional plating method, in order to propose an efficient, simplified,&#13;\nand suitable approach that could be useful for small industries to monitor constantly food quality.

The evolution and maintenance of public goods cooperation, despite cheating, remains a key interest in social biology. Identifying how ecological factors determine the direct and indirect benefits that maintain cooperation has proven challenging, as these can vary significantly across species and environments. Here, we study this problem using the social pine sawfly Neodiprion sertifer (Hymenoptera) as a model system. During their larval stage, N. sertifer live in groups and collectively secrete a defensive fluid against predators. This behavior comprises a public good as it is costly to exhibit and beneficial to others, and individuals vary in their contribution to group defense. We experimentally manipulated individual contributions to defense to assess how these influence survival under natural insect predation. Our results indicate that defense has a group-level benefit as individuals were more likely to survive in cooperative groups with a higher proportion of defending larvae. Moreover, being able to deploy defensive fluid confers direct survival benefits. Genetic and phenotypic analyses of natural populations further show that kin selection promotes collective defense, as groups of larvae are often composed of full siblings. We also find that the contribution to defense is female-biased and diminishes in larger, more male-biased groups, and to some extent with decreased kinship, indicating that individuals adjust their contributions based on social context. Overall, we find that contribution to the collective defense provides both direct and indirect benefits and that individuals regulate their contributions mainly based on the social environment, resulting in variation within and among natural populations.

Updated clinical practice guidelines for the management of adult diffuse gliomas.