Background: The incidence of early-onset colorectal cancer (EOCRC) is rising globally, yet its underlying risk factors remain incompletely understood, particularly in cases without recognised hereditary syndromes. Objectives: To update and synthesise the current body of evidence on modifiable and non-modifiable risk factors for sporadic early-onset colorectal cancer. Methods: A systematic review of peer-reviewed articles published in English reporting original observational research examining risk factors for sporadic early-onset colorectal cancer (<50 years old) was conducted. PubMed and EMBASE databases were searched from inception to March 2025. Across studies, effect measures varied; therefore, the synthesis focused on the consistency of associations rather than the direct comparison of effect sizes. Results: The initial search identified 2575 papers; 34 studies were included after screening. Several consistent associations were identified, with dietary and lifestyle factors along with metabolic conditions emerging as key risk factors. EOCRC risk was higher in males (adjusted odds ratio (aOR) 1.36–2.21 across studies), individuals of Caucasian ethnicity (aORs 1.48–2.56), and in individuals whose age was approaching 50 years (per year, aORs 1.05–1.11). Putatively sporadic EOCRC was associated with a family history of CRC or other cancers (aORs up to 8.61). Other key factors linked to higher risk included obesity (aORs 1.92–2.88; adjusted Hazard Ratios (aHRs) 1.04–1.82), metabolic syndrome (aORs 1.25–2.48; aHRs 1.2–1.26), diabetes (aORs 1.24–3.42), Western dietary patterns (aORs 1.84–2.99), and sedentary behaviours (adjusted relative risks (aRR) 1.69–2.44). Moderate-to-vigorous exercise appeared protective (aORs 0.34–0.58), as did higher vitamin D levels (aHRs 0.41–0.61). Evidence for smoking, alcohol, medications and early/in utero environmental exposures was inconsistent. Conclusions: Lifestyle and metabolic factors, including Western dietary patterns, obesity and sedentary behaviours, were associated with sporadic EOCRC. Family history also emerged as a significant contributor to putatively sporadic disease, suggesting heritable influences beyond recognised syndromes and interplay between environmental factors and genetic predisposition. Future research should focus on integrated tumour and germline profiling, including broader genomic analyses in well-characterised cohorts, to better understand potential pathogenic mechanisms and support the development of risk stratification approaches.

Aim: The management of low-grade gliomas (LGGs) is evolving with new insights into disease biology. Furthermore, recently, the phase III INDIGO¹ study highlighted the benefits of an IDH inhibitor, vorasidenib, in treating residual or recurrent grade 2 IDH-mutant gliomas following surgery alone. We aimed to characterise the current patterns of care for patients with LGGs in Australia and New Zealand, including the role of vorasidenib. Methods: An online survey examining respondents’ practice setting, caseload, and preferred treatment approach to three clinical scenarios was distributed through the Cooperative Trials Group for Neuro-Oncology, New Zealand Aotearoa Neuro-Oncology Society, and the Australian and New Zealand Society for Neuropathology in December 2023 with three reminders in April, June, and September of 2024. Results: The survey response rate was 19.6% (57/291), 87.7% from Australia, and 12.3% from New Zealand, spanning medical oncology (45.7%), pathology (22.8%), radiation oncology (17.5%), and neurosurgery (14.0%). Case 1 examined an IDH-mutant grade 2 astrocytoma following gross total resection. Observation alone was recommended by 93%. Case 2 examined an incompletely resected IDH-mutant grade 2 astrocytoma. If feasible, 38% recommended further surgery and 83% adjuvant chemotherapy and radiotherapy. After 12 months of disease stability, 53% of the respondents preferred vorasidenib over the existing therapies. Case 3 examined an incompletely resected IDH-mutant grade 3 oligodendroglioma. No respondents recommended observation alone, with 26% recommending salvage surgery and 97% recommending further chemotherapy and radiotherapy. Conclusions: This study describes current management practices for LGGs in Australia and New Zealand, showing ongoing variation and a cautious approach to integrating IDH inhibitors. This highlights the critical role of multidisciplinary team-based decision-making in increasingly complex clinical situations.

Introduction: Immunotherapy is well‐established in treating metastatic non‐small cell lung cancer (mNSCLC); however, data regarding acquired resistance and long‐term outcomes are limited. We examined long‐term outcomes in mNSCLC patients with ongoing treatment response at 2 years (long‐term responders) post‐treatment commencement. Methods: This multi‐center retrospective study identified mNSCLC patients treated with first‐ or second‐line immunotherapy±chemotherapy. Endpoints included progression‐free survival (PFS) and overall survival (OS), stratified by PD‐L1 tumor proportion score (TPS) (< 50% vs. ≥ 50%), treatment duration, and treatment line. Results: Of 354 patients, 52 (15%) long‐term responders were identified for analysis. Among them, median age was 68.5 years (28–87); the majority had an ECOG performance status ≤ 1 (81%), high‐PD‐L1 TPS (52%), and adenocarcinoma histopathology (83%). Most (73%) received immunotherapy first‐line. Median treatment duration was 23.5 months (1–80), and 19% prematurely ceased treatment. With a median follow‐up of 39 months from treatment commencement (95% CI 37–49), 15 (29%) patients had progressive disease, and 3‐year PFS was 78%. Oligo‐progression was common (87%), with lung/pleural disease (53%). Most received subsequent treatment (local therapy alone: 53%, systemic therapy alone: 20%, combined: 20%, supportive care: 7%) and achieved disease control (86%). Long‐term toxicities occurred in 44% and were predominantly endocrinopathies (83%) requiring ongoing management. Three‐year OS was 93%. Survival outcomes were unaffected by treatment duration, PD‐L1 TPS, and treatment line. Conclusions: Long‐term responders showed favorable survival outcomes, with most maintaining disease control with local therapies even after progression. This held true regardless of treatment duration, PD‐L1 TPS, or treatment line. Endocrinopathies were common long‐term toxicities.

Background: Oncogene‐driven metastatic non‐small cell lung cancer (mNSCLC) is associated with poor survival outcomes, despite advancements in first‐line tyrosine kinase inhibitor (TKI) therapies. Aims: This study aimed to characterise second‐line treatment strategies for epidermal growth factor receptor (EGFR)‐driven mNSCLC, and to evaluate associated clinical outcomes using real‐world data. Materials: The EnRICH study prospectively collected clinical data on patients diagnosed with lung cancer from NSW, Australia. Patients with EGFR‐driven mNSCLC who received second‐line therapy following progression on first‐line EGFR‐TKI were included in this analysis. Outcomes assessed included progression‐free survival (PFS2) and overall survival (OS), measured from second‐line treatment. Results: Of 2000 patients with newly diagnosed lung cancer, between 2016 and 2021, 1720 had NSCLC and 679 had metastatic disease. Among these, 647 underwent molecular testing, with 133 harboring an EGFR mutation. Of these 133, 80 patients received first‐line TKI therapy. From this group, 68 who subsequently received second‐line treatment following disease progression on first‐line TKI were included in this analysis. Of these 68 patients, 77% ( n = 52/68) were treated with a first‐ or second‐generation TKI (Erlotinib: n = 39, Gefitinib: n = 7, Afatinib: n = 6) in the first‐line setting. The remaining 16 patients received the third‐generation TKI Osimertinib. Of the total 68 patients in this cohort, in the second‐line setting, 45 patients underwent a change in their systemic therapy, and the remaining 23 patients received radiotherapy either with cessation of first‐line TKI ( n = 11) or in addition to continuation of first‐line TKI ( n = 12). Of the 45 patients who underwent a change in their systemic therapy, 32 received systemic therapy alone in the second‐line setting and 13 received radiotherapy in addition to a change in systemic therapy. Of these 45 patients, 33 received a TKI, with the majority receiving Osimertinib ( n = 28). Median PFS2 was 3.0 months (95% CI: 1.32–5.49), with no significant difference between patients treated with second‐line TKI and those receiving other therapies ( p = 0.24). Median OS was 15.0 months (95% CI: 13.24–23.66) and similarly did not differ significantly between second‐line TKI and alternative treatment strategies ( p = 0.17). Conclusions: Using real‐world data from EnRICH, this represents the largest retrospective analysis of this cohort in Australia and largely predates first‐line Osimertinib use. Findings reveal a trend toward second‐line Osimertinib use, even after first‐line TKI, without significant differences in survival. There, however, remains significant heterogeneity in approaches. The lack of robust second‐line data, however, highlights the need for investigating novel therapeutic approaches.