Physician barriers and dilemmas in the execution of clinical trials impacting decision-making in the DAHANCA 35 proton therapy trial for head and neck cancer.

Background: Physicians manage multiple obligations, providing best-practice treatment and patient- centred care in the standard treatment pathway while contributing to clinical trials simultaneously. These multifaceted responsibilities may introduce barriers and dilemmas to clinical trial execution, potentially impacting the clinical trial decision- making process. This study explores physicians' barriers and dilemmas in executing clinical trials and the impact on clinical trial decision-making. Method: Qualitative semi-structured interviews were conducted with experienced oncologists. Moreover, participant observations were performed during clinical encounters involving discussions about clinical trials. The analysis followed a structured approach: (1) transcription of data, (2) inductive text coding, (3) exploration of patterns, and (4) interpretation, leading to the results. The results were discussed and validated by the study participants. Results: The results comprise (1) a description of the clinical practice, which presents the setting of clinical trial execution; (2) results regarding physicians' barriers and dilemmas in executing clinical trials, leading to (3) the impact on clinical trial decision- making. The results involve barriers to time constraints for clinical trial tasks, dilemmas emerging from trial requirements or deviations from standard guidelines, and challenges with providing sufficient trial communication and adequate decision-making support, balancing between a paternalistic approach and respecting patient autonomy. Conclusion: The demanding obligations of clinical practice constitute a complex setting for executing clinical trials, resulting in numerous barriers and dilemmas that impact the decision-making process in clinical trials. The study emphasises the need for tailored clinical trial decision-making interventions to facilitate supportive, informed, and non-directive clinical trial decision-making.

Radiation therapy in older patients with cancer.

The general population is aging, which expectedly will lead to a future increase in older patients with cancer. This review summarises the recent advances in radiotherapy. Technological advances have led radiotherapy to be an efficient and well-tolerated treatment option in older patient with cancer. Studies show no difference in toxicity and disease control rates compared with the ones in younger patients with cancer. MR-guided radiotherapy, proton therapy, and integration of artificial intelligence in treatment planning represent the latest advances in the field of radiotherapy and hold potential to further improve the treatment of older patients with cancer.

Exploring patient-reported barriers to participating in proton therapy clinical trials.

Introduction: Clinical trials lead the progress in healthcare. To ensure reliable research conclusions, it is essential to enroll diverse patient groups. Identifying and understanding patient-reported barriers to clinical trials may help enhance recruitment among diverse patient groups.The clinical potential of proton therapy (PT) to reduce late effects is being investigated in clinical trials worldwide. Thus, for some patients, PT is only accessible by participating in clinical trials.Individuals with smoking-related head and neck cancer (HNC) are sometimes socioeconomically deprived, leading to barriers to trial participation. This study aims to identify barriers to their participation in a randomised controlled trial (RCT) involving PT. Method: Interviews were conducted with 14 HNC patients declining participation in an RCT involving PT. The interviews were transcribed and systematically analysed using an inductive approach identifying categories and themes. Results: The identified barriers to RCT-participation are: (1) existential distress, which influenced participants' mental and cognitive capacities, (2) insufficient RCT-related knowledge arising from information overload during clinical consultations, (3) the wish for safety and familiarity during the treatment trajectory, particularly for participants needing accommodation during  radiotherapy, and (4) the motivation for study participation was impacted by uncertainty due to randomisation and clinical equipoise. Existential distress is identified as an overarching theme because it influences and amplifies the other three themes. Conclusion: Existential distress is a central theme that influences and amplifies other participation barriers in PT RCTs. It affects participants' comprehension of trial information, their preference for familiar environments, and their motivation to participate in clinical trials.

Relationships of crystallinity and reaction rates for enzymatic degradation of poly (ethylene terephthalate), PET.

Biocatalytic degradation of plastic waste is anticipated to play an important role in future recycling systems. However, enzymatic degradation of crystalline poly (ethylene terephthalate) (PET) remains consistently poor. Herein, we employed functional assays to elucidate the molecular underpinnings of this limitation. This included utilizing complementary activity assays to monitor the degradation of PET disks with varying crystallinity (XC), as well as determining enzymatic kinetic parameters for soluble PET fragments. The results indicate that an efficient PET-hydrolase, LCCICCG, operates through an endolytic mode of action, and that its activity is limited by conformational constraints in the PET polymer. Such constraints become more pronounced at high XC values, and this limits the density of productive sites on the PET surface. Endolytic chain-scissions are the dominant reaction type in the initial stage, and this means that little or no soluble organic product are released. However, endolytic cuts gradually and locally promote chain mobility and hence the density of attack sites on the surface. This leads to an upward concave progress curve; a behavior sometimes termed lag-phase kinetics.