Papillary craniopharyngioma (PCP) and adamantinomatous craniopharyngioma (ACP) are distinct, slow growing tumors of the suprasellar region. Their location, composition and biology have historically evaded successful surgical, radiation, and medical therapy. Meanwhile compromise of critical structures either by tumor or treatments increase morbidity, impacting patient and carer quality of life. There has been a paradigm shift in the management of PCP, stemming from the discovery of BRAFV600E mutation in its tumorigenesis. Such a treatment breakthrough may soon be the case for ACP, changing the landscape of craniopharyngioma management. We use a case of ACP, partially responding to ERK inhibitor therapy to demonstrate chronicity of disease progression and discuss modern management strategies highlighting the importance of access to tumour agnostic clinical trials, and future directions.

PURPOSE: Early-phase clinical trials (EP-CTs) provide access to novel therapeutics for patients with limited standard treatment options. Beyond drug-related risks, participants may experience hidden toxicities, including time, financial, and social burdens that often go unmeasured. METHODS: The Patient Experience in Early-Phase Cancer Clinical Trials (PEARLER) study aimed to assess time, financial, and social toxicity (ST) in a prospective, multicenter cohort. Participants completed a time toxicity (TT) survey and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 on day 1 of cycles 1-6. Financial toxicity (FT) was assessed using the EORTC scoring manual; ST was evaluated using the social and role functioning domains. Multilevel models examined trends over time. RESULTS: A total of 122 participants (median age 62 years, range, 25-83) were enrolled. Median objective TT was 26%. Only 16% (20/122) reported subjective TT, most commonly during cycles 1-2 (85%). FT was reported by 44% (54/122), but did not significantly change over time ( P = .136). Although 71% (87/122) reported some reduction in social function, social functioning scores remained stable throughout trial participation. Role functioning declined in participants age 60 years and younger but was maintained in those older than 60 years. CONCLUSION: To our knowledge, PEARLER is the first prospective study to assess TT, FT, and ST in Australian EP-CTs. Although objective time burden was measurable, few patients perceived it as problematic beyond early cycles. FT and ST were commonly reported but remained stable over time. These findings suggest that EP-CT participation may not negatively affect patient-reported quality-of-life domains and provide reassurance for both clinicians and patients considering enrollment.

Background: Early phase clinical trials continue to have difficulty with enrolling real-world populations with many minorities being underrepresented. Reasons for this include patient or clinician perception as well as cultural, linguistic, or social barriers. In Australia, there is currently no prospective data in the early phase clinical trial space regarding recruitment of priority populations. Methods: Patient Diversity in Early Phase Clinical Trials was a multicenter, prospective, cohort study involving 2 major early phase clinical trial centers in Sydney, Australia. All participants who were consented to an early phase clinical trial between August 2023 and August 2024 were enrolled. Participants completed a baseline demographic survey, which included cultural and linguistic status, sexual orientation, socioeconomic status, and regional diversity. Results: A total of 114 participants were recruited. Median age was 63 years (range = 25-83 years) with predominance for female participants (52%). No participant reported a nonbinary gender. All participants reported their sexuality as heterosexual, with no LGBTQIA+ participants recruited. A total of 34 (30%) participants were identified as culturally diverse, while 28 (25%) were linguistically diverse. One patient identified as Indigenous Australian. Of the participants, 26% were born overseas, with 44% having at least 1 parent born overseas. The majority were living in households with family members, with 8% of participants living alone. Conclusion: Patient Diversity in Early Phase Clinical Trials is the first prospective study that provides granular description of social, cultural, linguistic, economic, and sexual diversity among early phase clinical trial participants. Certain subgroups are underrepresented, including those with sexual diversity, gender diversity, and Indigenous backgrounds. Ongoing efforts to monitor and promote inclusion of diverse populations in clinical trials are vital.

Purpose: Access to early-phase clinical trials (EPCT) is increasingly constrained by delays in genomic testing and lack of coordinated system-level navigation. The New South Wales Early Phase Clinical Trials Alliance (NECTA) was established to improve EPCT access. Practical Assessment of NECTA Network Assistance in Cancer Outpatient Trials Access (PANNA-COTA) prospectively evaluated whether integrating circulating tumor DNA (ctDNA) profiling with a real-time, cross-site molecular tumor board (MTB) facilitates EPCT enrollment. Patients and Methods: In this multicenter prospective study across nine NECTA sites, patients referred for EPCT consideration underwent ctDNA testing using the Guardant360 74-gene assay. The results were reviewed at a fortnightly MTB incorporating cross-site trial mapping and dynamic eligibility review. The primary endpoint was proportion enrolled into EPCTs. Secondary endpoints included ctDNA findings and trial outcomes. Results: Of 104 consented participants, 101 were eligible. Participants had advanced, heavily pretreated solid tumors; 48% lacked prior tumor next-generation sequencing. ctDNA alterations were detected in 85%, with actionable alterations in 44%. Therapeutic options were identified in 88%, and EPCTs were recommended in 76%. Despite this, only 7% of participants received genomically matched therapy. In contrast, 37% enrolled in EPCTs within 3 months and 47% overall [95% confidence interval (CI), 0.37–0.56]. Among evaluable participants on trial, the disease control rate was 81% and objective response rate was 33%. Conclusions: PANNA-COTA demonstrates that integrating liquid biopsy with real-time, network-level trial navigation enables high rates of EPCT enrollment despite low rates of genomically matched therapy. These findings indicate that clinical trial access is influenced by navigation, eligibility, and system-level coordination rather than genomic actionability alone.

Introduction: Health-related quality of life (HRQoL) is not routine in early phase clinical trials (EP-CTs), which focus on dose-limiting toxicities and safety. However, for clinicians, understanding the impact of such trials on HRQoL is fundamental to consent patients, especially when the benefits on tumor response may be unknown. Aims and Methods: The PEARLER (Patient diversity And experience in eaRLy phase cancEr clinical tRials) study was conducted with a key aim of focusing on assessing HRQoL in participants undergoing EP-CTs using a multi-center prospective cohort setting. All participants completed a baseline demographic survey on Cycle 1 Day 1 with EORTC-QLQ-C30 on Day 1 of Cycles 1 through 6 or end of treatment (EoT). Results: Overall, 122 participants were recruited with median age 62. Median baseline Global Health Status (GHS) was 67 and remained unchanged throughout EP-CT (P = .188). GHS deterioration occurred in 29/122 (24%) while improvement occurred in 16/122 (13%). Median baseline Physical Function Score (PFS) was 87. PFS deterioration occurred in 30/122 (25%) while improvement occurred in 6/122 (5%). Baseline median CFS was 84. Cognitive Function Score (CFS) deterioration occurred in 25/122 (20%) while improvement occurred in 20/122 (16%). Baseline median Emotional Function Score (EFS) was 77. EFS deterioration occurred in 14/122 (11%) while improvement occurred in 14/122 (11%). Presence of liver metastases was a negative predictive marker for GHS, CFS, and EFS over time (P = .01, P < .01, and P < .01). Conclusion: PEARLER is the first prospective cohort study investigating change in HRQoL over time in patients undergoing EP-CTs. Reassuringly, almost three-quarters of participants who undertake EP-CTs either sustain or improve their GHS or PFS. Presence of liver metastases appears to be a negative predictive marker of HRQoL.

Background/Objectives: Early-phase clinical trials (EPCTs) focus on safety and preliminary efficacy, often assessed by RECIST (Response Evaluation Criteria in Solid Tumours) tumour response. Health-related quality of life (HRQoL) is rarely evaluated in EPCTs and may not align with radiological outcomes. Methods: The PEARLER (Patient Experience in Early-Phase Cancer Clinical Trials) study evaluated the demographics, tumour response, HRQoL, and therapy type in two early-phase trial units in Australia between August 2023 and 2024. Patients completed the EORTC QLQ-C30 at baseline and follow-ups. The Global Health Status (GHS) score was selected as the primary HRQoL measure. Tumour response was assessed using RECIST 1.1. Spearman correlation and Kruskal–Wallis testing assessed the associations between RECIST, cross-sectional GHS change (ΔGHS; follow-up minus baseline), and therapy types. Multilevel models were used to evaluate longitudinal GHS values per RECIST category. Results: Of 122 patients recruited to the PEARLER study, 74 patients had paired RECIST and HRQoL data (complete response (CR) n = 0; partial response (PR) n = 15; stable disease (SD) n = 39; progressive disease (PD) n = 20). The median change in GHS was zero across RECIST groups, with broad individual variability. Notably, 18 of 54 patients (33.3%) with stable or responding disease experienced HRQoL decline. Meanwhile, 10 of 20 (50%) patients with PD experienced stable or improving HRQoL. The best RECIST response and ΔGHS showed a weak but statistically significant negative relationship (Spearman ρ = −0.28, p = 0.017), with the Kruskal–Wallis test demonstrating χ² = 6.20 (p = 0.045), indicating modest group differences driven by the deterioration in PD patients. The multilevel model demonstrated a lower GHS in patients with PD, with no statistically significant interaction of GHS change over time with the RECIST response (p = 0.226). Conclusions: HRQoL change is largely independent of radiologic tumour response and therapy type in EPCT participants. Patients experienced a HRQoL decline despite tumour response. Incorporating patient-reported outcomes alongside RECIST and safety outcomes is important to fully capture the impact of investigational therapies and guide patient-centred trial designs.