As of 2025, 85% of the world population lives in countries typically associated with the Global South. Fifty percent of the world's population is under age 30. This article introduces the special issue on "Young Adult Life Courses in the Global South." It aims to provide a conceptual entry point for globally comparative research on young adult life courses. We systematize and contextualize key insights from the twelve contributions to this special issue, which were selected through an open call, on 1) relevant macro-structural conditions for young adult life courses in the Global South, 2) conceptualizing adulthood processes, including implications for young adults' agency. Based on the contributions to this special issue, we propose a comparative framework that focuses on the locally specific interplay between economic, normative, and temporal conditions for navigating social adulthood. Second, we summarize the authors' critiques of established concepts of young adulthood and highlight alternative conceptualizations that they employ, including their implications for young adults' agency. We close by outlining avenues for future research for a globally comparative research agenda on young adult life courses.

In 2022, 58 Clinical Quality Indicators (CQIs) covering key aspects of glioma care were developed for an Australian brain cancer registry via a Delphi process [1]. Evidence supports MDT-managed patients have higher concordance with treatment guidelines [2]. This study examines: 1) adherence to MDT discussions and treatment guidelines, and 2) feasibility of MDT data extraction. Data sources included hospital/oncology EMRs, MDT minutes, and correspondence. Thirty-nine of 58 CQIs related to high-grade glioma (HGG) were selected, covering ECOG, diagnostics, extent of resection, post-operative MRI, radiotherapy and chemotherapy. MDT discussions, trial screening, and key referrals (e.g. allied health, palliative care) were analyzed. For MDT – discussed cases, further analysis assessed receipt of guideline-recommended therapy (GRT) and reasons for non-completion. The study cohort diagnosed between 2016-2020 comprised 183 patients: WHO Grade IV glioma (n=159) and Grade III (n=22), anaplastic astrocytoma (n=15) and oligodendroglioma (n=7). MDT discussions at initial diagnosis were undertaken in 168/183 (92%) cases. Of those discussed, 129/168 (77%) completed GRT, 30/168 (18%) partially completed GRT, and 9/168 (5%) did not complete GRT. Primary reasons for incomplete GRT included disease progression (n=13/39, 33%), patient decision (n=12/39, 31%), death (n=6/39, 15%), change in performance status (n=2/39, 5%), clinical decision (n=2/39, 5%), other comorbidities (n=3/39, 8%) and a geographical move in patient care (n=1/39, 3%). Automated data extraction was feasible for referral to the MDT, radiotherapy details, demographics, age, and date of diagnosis. However, manual data extraction was needed for all other CQIs including MDT discussions, recommendations and GRT completion/reasons for incompletion. Aligning tailored documentation with information systems will improve the efficiency of capturing HGG CQIs, including MDT referrals and recommendations. While reasons for non-GRT delivery were feasible to identify, they required manual data extraction. Integrating CQIs into routine automated systems will support longitudinal outcome tracking and benchmarking across patient cohorts.

The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60

BACKGROUND/AIM:Early phase clinical trials (EPCTs) assess the tolerability of novel anti-cancer therapeutics in patients with advanced malignancy. Patient selection is important given the modest clinical benefit and time commitments for trials. Prognostic scores have been developed to facilitate identification of high-risk patients. This study aimed to compare five prognostic scores to predict survival for patients on an EPCT.PATIENTS AND METHODS:We performed a retrospective review of patients enrolled in EPCT at Liverpool Hospital, Sydney, from 2013 to 2023. Demographic, biochemical, and survival data were collected from electronic medical records. The score from five prognostic scoring systems (Royal Marsden hospital, MD Anderson Cancer centre, Gustave Roussy Immune, MD Anderson Immune Checkpoint Inhibitor and Princess Margaret Hospital Index) were calculated. Overall survival was measured using the Kaplan-Meier method and predictive discrimination was assessed using Harrell's c-index.RESULTS:A total of 218 patients across 36 EPCTs were included. The median overall survival was 9.8 months with 22% of patients dying in less than 90 days. Seventeen to thirty-four percent of patients were categorised as high-risk. The MDACC score obtained the highest predictability for overall survival for the whole cohort (c-index=0.67, 95%CI=0.62-0.72) and the immunotherapy-based cohort (c-index= 0.65, 95%CI=0.59-0.71). However, all scores performed similarly with a significant overlap in the confidence intervals.CONCLUSION:Our retrospective audit confirms the utility of prognostic scores to predict survival in an Australian EPCT cohort, with similar predictive discrimination across various scoring systems. Integration of these prognostic tools into EPCT screening processes may optimise benefits and reduce risks associated with EPCTs.

Older patients are often excluded from clinical trials with the majority of patients being between the ages of 18 and 64 [ [1] Shenoy P. Harugeri A. Elderly patients' participation in clinical trials. Perspect Clin Res. 2015; 6: 184-189 Crossref PubMed Google Scholar ]. This may be due to increased incidence of medical comorbidities in the older adults as well as poorer performance status, but often this is a result of clinical selection bias for suitability for clinical trials [ [1] Shenoy P. Harugeri A. Elderly patients' participation in clinical trials. Perspect Clin Res. 2015; 6: 184-189 Crossref PubMed Google Scholar , [2] Habr D. McRoy L. Papadimitrakopoulou V.A. Age is just a number: considerations for older adults in Cancer clinical trials. J Natl Cancer Inst. 2021; 113: 1460-1464 Crossref PubMed Scopus (20) Google Scholar ]. Early phase clinical trials (EPCTs) aim to assess the tolerability and toxicity profile of novel anti-cancer therapeutics. The primary goal is to determine dose limiting toxicity (DLT) in order to move forward within the drug development timeline. As a result, EPCTs are generally demanding trials for patients, with greater time commitments, more uncertainties regarding toxicities, and limited knowledge of therapeutic potential. Often patients who enrol into EPCTs have exhausted all standard of care options, and whilst EPCTs provide potential for tumour control, this may be at the cost of potentially unexpected toxicities. The survival outcomes of patients undergoing EPCTs have continued to improve over the past decade and the clinical benefit rate has reached almost 50% in some real-world data sets [ [3] Menon S. Davies A. Frentzas S. Hawkins C.A. Segelov E. Day D. et al. Recruitment, outcomes, and toxicity trends in phase I oncology trials: six-year experience in a large institution. Cancer Rep (Hoboken). 2022; 5e1465 Google Scholar ]. Age is not a typical exclusion criterion for enrolment into EPCTs with most protocols relying on Eastern Cooperative Group performance status (ECOG PS) scores and expected survival of over three months as the minimum criteria for recruitment. However, there is limited data exploring the outcomes of older adult patients who enrol into EPCTs. We conducted a 10-year retrospective clinical audit of all patients treated at the Liverpool Hospital Early Phase Trials Unit and explored the role of age as a determining factor for clinical outcomes.

In this chapter we argue that we need to take seriously that youth, as a sociological category, is not only constituted by life-course status and intersectional aspects of identity like race, class and gender, but also by place. One construct that we find particularly useful for exploring how historically constituted conditions differentiate young people's lives geographically, is the notion of the global south. Rather than understanding the global south primarily as a geographical region, it is better conceived as a historically forged political category, interpolated in the second half of the twentieth century, roughly referring to- but not quite commensurate with- parts of the world that were colonised. While former colonies differ from one another and the north-south binary is clearly false, material differences do exist on a global scale and can be described at a national and regional level, with implications for place-based characteristics of young people's lives. Circumstances that characterise the countries global south youth inhabit include increased population density, more limited access to income, other resources and support from the state, but higher rates of violence and inequality. In the final section of the chapter we outline a theoretical approach of navigational capacities that focuses on elements that characterise the lives of global south youth, with increasing relevance for young people everywhere. The concept of navigation allows for a framework that transcends the individual-social divide, looking at how young people deal with the here and now and exert agency through their imagined futures.

Youth represent a great part of humanity and have always been active and intriguing political actors, yet youth remain sidelined in international studies. Issues of social identity perception and its consequences have been embraced by post-positivist approaches in international studies. Yet, while race, gender, and class challenges are shaking the discipline, age is a key research gap. To fill this gap, the conceptual departure of this forum is to study youth, taking 16-30/35 as an age range, as "boundary actors" in international politics. We assembled contributions that address this conceptual departure on topics, including health, conflict, climate change, and indigenous people's rights, across all world regions with specific focuses on Africa and Asia. Overall, the forum demonstrates that youth are able to move the boundaries: (i) of norms in international politics by asking for a more inclusive implementation of human rights and/or environmental justice; (ii) of procedures by suggesting to broaden decision-making; (iii) of international activism by combining social media and protests as new strategies. Taken together, the contributions show that youth have and are a world-building project, not just a world-confirming project.

The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. Of the combined 205 patients, 57 (28

Introduction: Early phase clinical trials (EPCTs) enable access to novel therapies for patients who have exhausted standard of care treatment and contribute a crucial role in drug development and research. Culturally and linguistically diverse (CALD) or socially disadvantaged patients have notably lower rates of participation in these trials. We aimed to characterise the social and cultural demographics of patients enrolled on an EPCT in South Western Sydney. Methods: We conducted a 10-year retrospective review of patients enrolled on a EPCT at Liverpool Hospital. CALD patients were defined as those born overseas or whose preferred language was other than English. The patient residential address was used to calculate distance travelled, and the Index of Relative Socioeconomic Disadvantage (IRSD) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) scores were calculated and used as a surrogate for socioeconomic status (SES). Results: Our study included 233 patients across 39 EPCTs. Ninety-one patients (39%) were identified as CALD. The median IRSD and IRSAD scores were 941 and 944, respectively, with 62.7-67.4% of patients residing in an area with greater disadvantage compared to the median of Australia. The median distance travelled was 17 kilometres with only 12% of participants travelling more than 50 km. CALD patients were more likely to reside in an area of low SES (OR 3.4, 95% CI: 1.8-6.5, p < 0.01) and travelled shorter median distances (10 vs. 23 km) when compared to non-CALD patients. Conclusion: Our study cohort contained a lower proportion of CALD patients and a higher SES than what we might have expected from our local population. Furthermore, there was a trend toward greater SES disadvantage (lower IRSD/IRSAD scores) for the CALD population. This study provides novel Australian data to support the underrepresentation of culturally diverse or disadvantaged patients on EPCTs. Future efforts should be made to reduce barriers to participation and improve equity in clinical trial participation.

Supplementary Table 1 - Histomorphological characteristics of tumor samples taken prior to treatment (PRE), early during treatment (EDT) and on disease progression (PROG) in melanoma patients receiving anti-PD-1 therapy Supplementary Table 2 - Immune infiltrate flux from pretreatment value to early during treatment biopsies (fold change).

BACKGROUND:Senaparib is a novel, selective poly(ADP-ribose) polymerase-1/2 inhibitor with strong antitumor activity in preclinical studies. This first-in-human, phase 1, dose-escalation study examined the safety and preliminary efficacy of senaparib in patients with advanced solid tumors. METHODS:Patients with advanced solid tumors were enrolled from three centers in Australia, using a conventional 3 + 3 design. Dose-escalation cohorts continued until the maximum tolerated dose or a recommended phase 2 dose was determined. Patients received one dose of oral senaparib and, if no dose-limiting toxicity occurred within 7 days, they received senaparib once daily in 3-week cycles. The primary end points were safety and tolerability. RESULTS:Thirty-nine patients were enrolled at 10 dose levels ranging from 2 to 150 mg. No dose-limiting toxicities were observed in any cohort. Most treatment-emergent adverse events were grade 1-2 (91%). Seven patients (17.9%) reported hematologic treatment-emergent adverse events. Treatment-related adverse events occurred in eight patients (20.5%), and the most frequent was nausea (7.7%). Two deaths were reported after the end of study treatment, one of which was considered a complication from senaparib-related bone marrow failure. Pharmacokinetic analysis indicated that senaparib the accumulation index was 1.06-1.67, and absorption saturation was 80-150 mg daily. In 22 patients with evaluable disease, the overall response rate was 13.6%, and the disease control rate was 81.8%. The overall response rate was 33.3% for the BRCA mutation-positive subgroup and 6.3% for the nonmutated subgroup. CONCLUSIONS:Senaparib was well tolerated in Australian patients with advanced solid tumors, with encouraging signals of antitumor activity. The recommended phase 2 dose for senaparib was determined to be 100 mg daily. CLINICALTRIALS: GOV ID:NCT03507543.

e14591 Background: NOX66 (idronoxil) targets ENOX2 and suppresses STING-mediated inflammatory pathways, reducing IFN and NFκB driven cytokine production by cancer cells. Adding NOX66 to nivolumab may help overcome resistance mechanisms to checkpoint inhibitors and improve responses in patients. Methods: IONIC-1, is an open label Phase I/II trial evaluating safety and preliminary efficacy of NOX66 (suppositories daily x 1 week, then 1 week rest) combined with nivolumab (240mg IV every 2 weeks). Three dose cohorts of NOX66 are planned (1200mg daily, 1800mg daily, 2400mg daily). Objectives include safety, tolerability, and clinical and radiological responses. Two groups are being studied: 1) Pts who have prior progression on a checkpoint inhibitor; 2) Pts naïve to checkpoint inhibitors. Results: 11 pts have been treated to date; 3 in Group 1, and 8 in Group 2. All pts have received at least 2 cycles of the combination treatment; 2 pts completed 8 cycles, and 2 pts remain on study. Tumour types include lung, prostate, gastric, pancreatic, nasopharyngeal and metastatic squamous carcinoma. Early signals of tumour response based on RECIST 1.1 criteria include stable disease in 2 pts (SD at 8 weeks and at 16 weeks); partial response (PR) in 1 patient at 16 weeks; complete response (CR) in 2 pts, both with ongoing CR at 24 weeks. Five pts had disease progression, and 1 pt was withdrawn due to suspected immune mediated myositis and hepatitis resulting from nivolumab and was not evaluable. The most common AE was local perineal irritation, readily managed with topical corticosteroid cream. Two pts developed an erythematous rash over the trunk and limbs after 2 cycles, suspected to be related to the combination treatment. Using a 32 multiplexed immune cytokine assay to evaluate the single-cell functional states of CD4+ and CD8+ T cells in patients’ peripheral blood mononuclear cells (PBMCs) at pre-treatment and at Cycle 3 Day 1, we found a significant increase in polyfunctionality in both effector CD4+ and CD8+ve T cells compared to baseline in responder patients. Conclusions: Preliminary analysis shows promising tumour responses from the combination therapy which appears to be well-tolerated, with no safety signals evident to date. Clinical trial information: ACTRN12621001537842 .

Genetic histone variants have been implicated in cancer development and progression. Mutations affecting the histone 3 (H3) family, H3.1 (encoded by HIST1H3B and HIST1H3C) and H3.3 (encoded by H3F3A), are mainly associated with pediatric brain cancers. While considered poor prognostic brain cancer biomarkers in children, more recent studies have reported H3 alterations in adult brain cancer as well. Here, we established reliable droplet digital PCR based assays to detect three histone mutations (H3.3-K27M, H3.3-G34R, and H3.1-K27M) primarily linked to childhood brain cancer. We demonstrate the utility of our assays for sensitively detecting these mutations in cell-free DNA released from cultured diffuse intrinsic pontine glioma (DIPG) cells and in the cerebral spinal fluid of a pediatric patient with DIPG. We further screened tumor tissue DNA from 89 adult patients with glioma and 1 with diffuse hemispheric glioma from Southwestern Sydney, Australia, an ethnically diverse region, for these three mutations. No histone mutations were detected in adult glioma tissue, while H3.3-G34R presence was confirmed in the diffuse hemispheric glioma patient.