The Beatson West of Scotland Cancer Centre (BWSCC; formerly called the Beatson Oncology Centre) is a specialised cancer care centre in Glasgow, Scotland. Until recently it had facilities in Gartnavel General Hospital, the Western Infirmary and Glasgow Royal Infirmary. As part of the NHS Greater Glasgow and Clyde Acute Services Review, the centre is being centralised within new facilities at the Gartnavel General Hospital site.
Curative-intent multimodality treatment-combining local treatments such as surgery or radiotherapy with systemic therapy-is the cornerstone of care in stage II-III non-small cell lung cancer (NSCLC). Since 2017, the systemic therapy backbones with multimodality treatment have undergone a dramatic transformation, driven by a series of pivotal, practice-changing clinical trials. Immunotherapy and targeted therapies, previously confined to the advanced/metastatic setting, are now firmly embedded in curative-intent regimens. Maintenance immunotherapy following chemoradiation in unresectable stage III disease, adjuvant tyrosine kinase inhibitors in resected epidermal growth factor receptor/anaplastic lymphoma kinase-positive tumours, neoadjuvant and perioperative chemoimmunotherapy in resectable stage II/III NSCLC and adjuvant chemoimmunotherapy following resection have all become new standards of care.This state-of-the-art review synthesises the key evidence underpinning these developments, highlights their clinical implications and identifies challenges to implementation-particularly the need for redefined clinical pathways, accurate pretreatment staging, timely biomarker testing and coordinated multidisciplinary decision-making. A novel treatment algorithm is proposed to support clinicians in navigating these complex treatment choices.We conclude that immunotherapy and targeted agents have irrevocably altered curative-intent NSCLC care, establishing multiple new standards that sometimes overlap and compete. In the surgical multimodality treatment pathway, neoadjuvant and perioperative chemoimmunotherapy offers the opportunity to increase the uptake of systemic therapy in comparison to adjuvant therapy and is considered by these authors to represent the optimal treatment path for most patients.In this unprecedented era of therapeutic expansion, the greatest challenge is no longer the absence of effective treatments, but the complexity of selecting, sequencing and delivering them, as well as patient optimisation. Lung cancer services must evolve through proactive pathway redesign, integrated diagnostics and new models of multidisciplinary care. High-quality, biomarker-driven and patient-centred care is now achievable for many patients with stage II-III NSCLC-but it will require system-level adaptation to deliver it.
BACKGROUND:Transdermal estradiol (tE2) is an alternative to luteinizing hormone-releasing hormone (LHRH) agonists as androgen-deprivation therapy in patients with prostate cancer. With tE2, testosterone is suppressed, and the side effects of estrogen depletion due to LHRH agonists and the thromboembolic side effects of oral estrogen are mitigated. METHODS:In this phase 3, noninferiority, randomized trial, we assigned men with locally advanced (M0 and N0 or N+) prostate cancer to receive tE2 patches (100 μg of estradiol every 24 hours) or LHRH agonists. The primary outcome was 3-year metastasis-free survival. The noninferiority margin was 4 percentage points; this corresponded to a target hazard ratio of 1.31, as derived from the observed 3-year metastasis-free survival in the LHRH agonist group. Secondary outcomes included castrate levels of testosterone (<1.7 nmol per liter), overall survival, and safety. RESULTS:Between 2007 and 2022, we recruited 1360 patients at 75 U.K. centers. The median age of the patients was 72 years (interquartile range, 68 to 77); 85% had a T3 tumor stage and 65% an N0 nodal stage. Observed 3-year metastasis-free survival was 87.1% with tE2 and 85.9% with LHRH agonists (hazard ratio for confirmed metastasis or death, 0.96; upper limit of the one-sided 95% confidence interval [CI], 1.11, which met the criterion for noninferiority). Among patients continuing the assigned treatment, castrate levels of testosterone were sustained during the first year after randomization in 85% in each group. Observed 5-year overall survival was 81.1% with tE2 and 79.2% with LHRH agonists (hazard ratio for death, 0.90; 95% CI, 0.75 to 1.07). During treatment, hot flashes occurred in 44% of the patients who received tE2 and 89% of those who received LHRH agonists (grade ≥2 events, 8% and 37%, respectively) and gynecomastia in 85% and 42% (grade ≥2 events, 37% and 9%). CONCLUSIONS:In patients with locally advanced prostate cancer, tE2 was noninferior to LHRH agonists for 3-year metastasis-free survival, with a lower incidence of hot flashes but a higher incidence of gynecomastia. (Funded by Cancer Research U.K. and the U.K. Research Institute Medical Research Council; PATCH ClinicalTrials.gov number, NCT00303784; STAMPEDE-1 ClinicalTrials.gov number, NCT00268476.).
BACKGROUND:Adjuvant pembrolizumab improves disease-free and overall survival among patients with resected clear-cell renal-cell carcinoma. The hypoxia-inducible factor 2α inhibitor belzutifan has activity in advanced disease. Adjuvant pembrolizumab with belzutifan may further improve outcomes in patients with clear-cell renal-cell carcinoma at increased risk for recurrence. METHODS:In this phase 3, double-blind trial, we randomly assigned participants in a 1:1 ratio to receive intravenous pembrolizumab at a dose of 400 mg every 6 weeks (≤9 doses) and either daily oral belzutifan at a dose of 120 mg (pembrolizumab-belzutifan) or placebo (pembrolizumab-placebo) for up to 1 year. The primary end point was disease-free survival as assessed by the investigator; secondary end points included overall survival and safety. RESULTS:A total of 921 participants were assigned to receive pembrolizumab-belzutifan and 920 were assigned to receive pembrolizumab-placebo. The median time from randomization to the data-cutoff date (August 23, 2025) was 28.4 months (range, 15.0 to 40.1). Disease-free survival was significantly higher with pembrolizumab-belzutifan than with pembrolizumab-placebo (hazard ratio for disease recurrence or death, 0.72; 95% confidence interval [CI], 0.59 to 0.87; two-sided P<0.001); the estimated 24-month disease-free survival was 80.7% and 73.7%, respectively. At this interim analysis with 29% of the final-analysis events observed, overall survival did not differ significantly between the groups (hazard ratio for death, 0.78; 95% CI, 0.51 to 1.19; two-sided P = 0.24); the estimated 24-month overall survival was 96.2% with pembrolizumab-belzutifan and 95.7% with pembrolizumab-placebo. Adverse events of grade 3 or higher occurred in 52.1% of the participants who received pembrolizumab-belzutifan and in 30.2% of those who received pembrolizumab-placebo. CONCLUSIONS:Treatment with pembrolizumab-belzutifan led to significantly higher disease-free survival, with a greater risk of grade 3 or higher toxic effects, than treatment with pembrolizumab monotherapy after nephrectomy in participants with clear-cell renal-cell carcinoma at increased risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; LITESPARK-022 ClinicalTrials.gov number, NCT05239728.).
High-dose methotrexate (HDMTX) is a key component of induction therapy for a range of cancers, but can lead to serious adverse effects, including acute kidney injury (AKI). We report two cases of HDMTX use in haematological malignancies. Patient 1 was an 8-year-old girl with high-grade NHL. She received 3 courses of HDMTX (3 g/m2) without issue. For her 4th course, she developed AKI with creatinine peaking at 240 μmol/L after HDMTX administration. She required intensified hydration and antihypertensive therapy for fluid overload, received glucarpidase for delayed MTX clearance, required parenteral nutrition for mucositis and ultimately made a full recovery. Patient 2 was a 76-year-old man with primary central nervous system lymphoma. He underwent HDMTX treatment per the MARTA protocol with dose reductions due to renal impairment. He experienced delayed MTX clearance leading to fluid overload, acute liver injury, required prolonged diuretic and antibiotic therapy, and was hospitalised for 3 weeks before recovery. These cases emphasise the need for preemptive supportive care, including prehydration and folinic acid (leucovorin), careful monitoring and early intervention with glucarpidase in the event of toxicities.
INTRODUCTION:Intensity Modulated Radiotherapy (IMRT) and Image Guided Radiotherapy (IGRT) have become an integral part of standard care for rectal cancer, but evidence-based detailed guidance is lacking to support its clinical implementation and use. This European SocieTy for Radiotherapy and Oncology (ESTRO) technical guideline aimed to assess the available evidence and provide recommendations for their use in rectal cancer treatment. MATERIALS AND METHODS:The ESTRO Lower Gastrointestinal (GI) Cancer guidelines subcommittee formed a writing panel to address key questions (KQs) on the application of IMRT and IGRT in rectal cancer management. The panel conducted a literature review and where evidence was insufficient, expert consensus was used. RESULTS:The writing panel (2 RTTs, 2 medical physics experts, 3 radiation oncologists) identified 14 KQs. Recommendations were based on low to moderate evidence and/or expert consensus. Supine positioning is preferred for patient comfort and stability. Comfortable full bladder should be used. For OAR delineation and dose optimization, mandatory (Bladder, Bowel Cavity, Femoral Heads) and optional OAR were defined. Auto-delineation is supported for OAR and can be considered for target volumes. Dose metrics for minimizing gastrointestinal and genitourinary toxicity were identified. Auto-planning tools and MR-only workflows are feasible, both require proper QA. Uncertainties from setup and target volume shape variations must be accounted for with appropriately defined margins. Daily volumetric image guidance is recommended for treatment verification. CONCLUSION:This ESTRO technical guideline for the use of IMRT and IGRT for rectal cancer was developed to support development and implementation into clinics.
