Introduction Squamous cell carcinoma of the head and neck is the most common cancer in Sri Lanka, with around 4,000 new cases annually. While radiotherapy is a key treatment, its efficacy is limited by tumour hypoxia, which reduces radiosensitivity and promotes aggressive tumour behaviour. Radiobiological modelling suggests that a biphasic fractionation regimen of conventional fractionation followed by hypofractionation, could overcome hypoxia-related challenges and enhance treatment outcomes without increasing toxicity. Methods and analysis The HYPOCON pilot trial is an investigator-initiated, multicentre, open-label, randomised trial designed to assess the feasibility of delivering a biphasic fractionation regimen in patients with squamous cell carcinoma of the head and neck. A total of 46 participants will be recruited across four centres and randomised 1:1 to either the control or experimental arm. The control arm will receive 55 Gy in 20 fractions over 4 weeks, while the experimental arm will follow a biphasic fractionation schedule: Phase 1 involves 40 Gy in 20 fractions over 3 weeks and 3 days, followed by Phase 2 with 15 Gy in 3 fractions delivered on consecutive days. All participants will also receive concurrent chemotherapy with intravenous cisplatin. Participants will be followed up monthly during the first-year post-treatment and every two months in the second year. The primary objective is to assess the feasibility of delivering the experimental regimen. Secondary objectives include evaluating rates of grade 3 or higher acute and late toxicities, as well as response rates, disease-free survival, and overall survival. This trial aims to establish the groundwork for a larger definitive study to evaluate the efficacy of this novel biphasic fractionation approach.
Introduction Dose escalation may improve tumor control in prostate stereotactic body radiotherapy (SBRT), but its impact on patient-reported outcomes (PROs) remains unclear. We evaluated urinary and bowel PROs after prostate SBRT, focusing on the impact of dose escalation. Methods This single-institution retrospective cohort study included consecutive patients treated with five-fraction prostate SBRT between 2016 and 2024. The primary outcomes were EPIC urinary irritative/obstructive (EPIC-UIR) and bowel (EPIC-B) scores. Patients with at least one EPIC-UIR or EPIC-B assessment within 36 months after treatment were included. Prescribed dose varied over time according to institutional clinical practice. Patients were categorized into a lower-dose group (≤40 Gy) and a higher-dose group (>40 Gy). Linear mixed-effects models were used to evaluate longitudinal trajectories. Clinically meaningful deterioration was assessed using minimal clinically important difference (MCID)-based analyses in the acute (1- and 3-month timepoints) and late (6- to 36-month timepoints) phases. Results Among 940 patients treated with SBRT, 872 patients constituted the subjects of PRO analysis, including 672 in the lower-dose group and 200 in the higher-dose group. In both groups, urinary and bowel scores showed acute decline followed by early recovery. Compared with the lower-dose group, the higher-dose group showed less favorable late urinary outcomes in both longitudinal analyses (P < 0.001) and MCID-based analyses, with late urinary worsening observed in 68% versus 80% of patients (P = 0.007). Conclusion Dose escalation in prostate SBRT may involve a trade-off with late urinary PROs, highlighting the need for careful consideration of urinary organs at risk.
Background The APPROACH (Analysis of Proton vs Photon Radiotherapy in Oligodendroglioma and Assessment of Cognitive Health) trial is a UK randomised controlled study comparing photon RT with proton beam therapy (PBT) for oligodendroglioma, with a primary endpoint of neurocognitive function at five years. As part of the trial’s radiotherapy quality assurance (RTQA) programme, a national pre-accrual facility questionnaire (FQ) was undertaken to evaluate RT practices across England and Wales and assess readiness for protocol compliance. This study reports UK photon radiotherapy practice for oligodendroglioma and evaluates consistency relative to APPROACH protocol requirements. Methods Between December 2022 and September 2025, photon radiotherapy centres in England and Wales (n=23) and both UK proton centres completed the FQ. The questionnaire captured routine practice in immobilisation, imaging, contouring, planning, and verification. Responses were collated by the RTTQA Group. Results All centres routinely used thermoplastic mask immobilisation and delivered photon radiotherapy using IMRT/VMAT. Dose schedules were consistent, most commonly 54 Gy in28–30 fractions for WHO grade 2 oligodendroglioma and 59.4 Gy in33 fractions for grade 3.However, substantial variation was identified in pre-treatment imaging: CT slice thickness ranged from 1–3 mm and MRI T1 slice thickness from 0.8–3 mm, with nine centres exceeding the 1 mm protocol requirement. MRI type and sequencing were inconsistently reported, and not all centres used dedicated planning MRI scans.Marked variability was also observed in organ-at-risk (OAR) contouring. While optic pathway structures and brainstem were routinely delineated, only 4/23 (17%) centres contoured hippocampi, and none contoured the hypothalamus as standard practice. Auto-contouring tools were used in 65% of centres. Conclusions The findings indicate broad alignment in technique and dose delivery but highlight variability in imaging and OAR delineation. Implementation of the APPROACH trial and associated RTQA processes is hoped to promote national standards in oligodendroglioma RT practice.
Background Locoregional recurrence (LRR) of breast cancer, comprising ipsilateral breast tumour recurrence (IBTR), chest wall recurrence after mastectomy (CWR), and regional nodal recurrence including axillary nodal recurrence (ANR), internal mammary node (IMN) recurrence, and supraclavicular (SCV) recurrence, is a significant challenge for patients previously cured from breast cancer. LRR may be surgically resectable or present as locally advanced unresectable disease. There is limited evidence to guide the management of LRR in breast cancer and it requires a multidisciplinary approach. The aim of this review is to synthesize the current evidence and identify gaps in the literature. Methods MEDLINE/PubMed, JAMA Network, Annals of Oncology/ESMO, NCCN educational materials, ASTRO/Advances in Radiation Oncology, Clinical Oncology, and key oncology journals were searched (Jan 2010–Oct 2025) for guidelines, RCTs, prospective trials, large retrospective series, and meta-analyses focused on LRR after prior curative treatment. Outcomes of interest included local control (LC), disease-free survival (DFS), distant metastasis-free survival (DMFS), overall survival (OS), toxicity, and quality of life (QoL). Preference was given to randomised and prospective evidence where available (e.g., CALOR; NRG/RTOG 1014). Results The management of LRR depends on the resectability of the disease. If a negative margin can be achieved, then curative surgical options should be considered. Following surgery, adjuvant systemic therapy (chemotherapy, anti-HER2 therapy, endocrine therapy) may be considered, although evidence specific to LRR is limited. Radiotherapy can also help with local control as well as symptom management. If LRR is unresectable, it should be treated similarly to metastatic disease with the treatment tailored to the molecular subtype. Conclusions There is limited evidence guiding the management of LRR in breast cancer. Surgical resectability remains the best prognostic factor and offers a potential cure. Systemic therapy and radiotherapy depend on disease biology and careful examination of the recurrence allows optimal management. Biopsy confirmation and biomarker reassessment are essential because discordance is common.
Purpose Our institution regularly offers accelerated partial breast irradiation (APBI) 3000 cGy in 5 fractions. This study compares dosimetry and acute toxicities between patients treated in the prone vs supine positions. Methods We retrospectively reviewed all patients with in-situ or invasive breast cancer treated with 3000 cGy in 5 fractions APBI at our institution between January 2022 and December 2023. We obtained dosimetric and acute toxicity data for each patient. Differences between treatment groups were analyzed using Wilcoxon rank sum, Pearson's Chi-squared and Fisher’s exact tests. Results A total of 168 patients were identified, 134 (79.8%) treated prone and 34 (20.2%) treated supine. Of the supine patients, 23 (67.6%) were treated with photon-only plans and 11 (32.4%) with mixed photon-electron plans. There were no statistically significant differences in age, BMI, tumor size, or breast laterality between the two groups. PTV volume was larger for prone patients (p=0.002). Target coverage was excellent and similar in both positions. Ipsilateral breast dosimetry did not differ significantly between groups. Median mean heart dose (MHD) was significantly lower in prone patients (9.6cGy vs 14.9cGy, p=0.033). This difference was more pronounced in right-sided patients vs left-sided patients (right: 6.9cGy prone vs 8.6cGy supine, p=0.037; left: 17.6cGy prone vs 16.5cGy supine, p=0.710). MHD was also significantly higher in mixed photon-electron plans (22.5cGy) vs supine photon-only plans (10.6cGy) p=0.009. Mean ipsilateral lung V10Gy was lower for prone patients (0.28% vs 1.44%, p=<0.001). Grade 1-2 dermatitis was more frequent in the supine cohort (p=0.029). Fatigue was significantly higher in patients with BMI ≥30 vs patients with BMI <30 (p=0.035). Conclusions Both treatment positions were safe, and there were no differences in target coverage or ipsilateral breast dosimetry between the two groups. Prone positioning was associated with lower heart and lung doses as well as lower rates of acute dermatitis, but heart and lung doses were minimal regardless of treatment position.
AIMS:Retrospective comparative dosimetric evaluation using anonymized patient datasets for stereotactic brain radiotherapy delivered using robotic radiosurgery, ring-gantry helical delivery, and C-arm linear accelerator-based volumetric modulated arc therapy (VMAT), with particular emphasis on the impact of increasing intracranial lesion number on low-dose spillage and organ-at-risk exposure. MATERIALS AND METHODS:Treatment plans were generated using clinically contoured intracranial metastases derived from patient datasets, with lesion-burden scenarios ranging from 1 to 20 lesions across all platforms. Ring-gantry plans were created using a 2.5 cm field width. VMAT with both single- and multi-isocenter approaches in coplanar and noncoplanar configurations were used. All plans were prescribed 27 Gy in three fractions and optimized to achieve 100% of the dose to 98% of the planning target volume (PTV). Dosimetric endpoints included low-dose spillage volumes (V5Gy, V10Gy, V12Gy, and V15Gy) and V20Gy for the whole brain. Additional organ at risk (OAR) doses to the hippocampus, brainstem, and optic apparatus were evaluated. Treatment efficiency was assessed using monitor units and beam-on time. RESULTS:Clinically acceptable target coverage was achieved across all platforms. Increasing lesion number led to a progressive increase in low-dose spillage across all techniques, with distinct platform-specific trends. CyberKnife demonstrated lower low-dose spillage but required substantially longer treatment times, whereas VMAT provided efficient delivery for higher lesion counts but showed greater increases in V5-V15 Gy with increasing lesion burden. CONCLUSION:Lesion burden was strongly associated with low-dose spillage and OAR exposure in multilesion brain stereotactic radiotherapy. These findings provide comparative dosimetric insights within the evaluated treatment platforms and may support individualized planning decisions when balancing low-dose exposure and delivery efficiency.
Introduction Sotorasib is an oral, potent, selective inhibitor. It is approved for the treatment of patients with KRAS G12C mutation positive, locally advanced or metastatic NSCLC. Real world safety and efficacy data are essential to understand the clinical potential of Sotorasib. Methods Retrospective Real World Evidence (RWE) was collected for UK patients with KRAS G12C mutation positive, locally advanced or metastatic NSCLC who had received Sotorasib (n=150) at 20 hospitals. Demographics, histopathology stage, PD-L1 status, metastatic disease including CNS, ECOG performance status (PS) and toxicity markers were reviewed. PFS, OS and response rates were calculated. Results Patients were aged 41-93 years (median age: 68 years; 15/150 were >80 years); 21% had a ECOG PS=2. Most (79%) were former smokers. 98% had adenocarcinoma and 83% had metastatic disease.UK RWE was compared with data from the open label, phase 3 Sotorasib trial (CodeBreaK 200). In the UK RWE, the median rwPFS was 7.0 months (95% CI 5.76-8.30); in CodeBreaK 200, median PFS was 5.6 months (95% CI 4.3-7.8). The median rwOS in the UK RWE was 9.54 months (95% CI 8.47-10.60) versus 10.6 months (95% CI 8.9-10.4) for mOS in CodeBreaK 200. Treatment cessation due to AEs occurred in 20/131 UK patients (15.3%) versus 16/169 (10%) in CodeBreaK 200. Discussion The shorter median rwOS and higher rate of treatment cessation may reflect the higher proportion of older and frail patients in the UK RWE dataset compared to CodeBreaK 200. Conclusions The UK RWE aligns with the results of CodeBreaK 200.
Aim Radiotherapy provides an effective radical treatment approach for a range of cancers. Despite technical advancements improving survival rates, many patients experience acute and late radiotherapy toxicities. Radiotherapy late effects (RLEs) present months or years following treatment, and present a significant physical, psychosocial and emotional burden. The radiotherapy service specification calls for RLEs to be managed locally; however, provision of specialist support for RLEs across England is lacking. Encouragingly, RLE-specific services have been introduced to diagnose and manage RLEs and provide holistic support. Few studies have explored how RLE services are configured, funded and staffed. This study sought to evaluate the current provision of RLE services across England and barriers to further service development. Materials and methods An online survey was developed using Microsoft Forms and disseminated to all 52 radiotherapy service providers across England. Descriptive statistics were used to analyse quantitative data, whilst inductive thematic analysis was conducted to identify key themes within qualitative responses. Results 31 responses were received, providing a response rate of 60%. 55% (n = 17) had an established RLE service and were mostly led by Therapeutic Radiographers. Most services managed pelvic RLEs, whilst few provided support for other disease sites. All RLE services accepted referrals from secondary care; however, primary care and patient self-referrals were less common. Most services were NHS-funded (71%, n = 12), whilst 24% (n = 4) relied on charitable funding. Qualitative comments highlighted challenges associated with staffing and insufficient funding. Conclusion These findings provide an initial insight into RLE services across England, revealing significant regional variation. To achieve equitable access and support for all patients, a revised approach to workforce modelling and commissioning of RLE services is urgently required. Here, we provide recommendations to support future development and sustainability of RLE services. Addressing the barriers identified within this study is imperative to improve survivorship outcomes nationwide.
AIM:Definitive chemoradiotherapy (dCRT) is a standard of care for locally advanced oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC). Following dCRT, many patients develop local residual or recurrent disease that is resectable via an endoscopic route. This avoids the need for an oesophagectomy, for which many patients are unfit and which is morbid. However, the toxicity and efficacy of post-radiotherapy endoscopic salvage has not been systematically assessed. MATERIALS AND METHODS:A systematic review was undertaken in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance. PubMed, Medline, Cochrane Library, Scopus, Web of Science and EMBASE databases were searched for terms relating to the endoscopic management of residual or recurrent disease following dCRT in oesophageal cancer. Data relating to tolerability, toxicity and efficacy were extracted from studies published between January 1990 and December 2025. RESULTS:After screening, 45 studies were included, describing endoscopic management of 1970 residual or recurrent lesions (n = 976 endoscopic resections, n = 548 photodynamic therapy). Most (n = 43/45) focused on OSCCs. Reported overall survival at 3- and 5- years post-salvage ranged from 35-81% and 36-75%, respectively. The most frequently reported adverse events following endoscopic resection was stricture, in 0-21% of cases. There were no deaths in this group but five reported following photodynamic therapy, for which the most frequent adverse event was chest pain, in 25-54.9% of the population. No studies reported health-related quality of life measures. CONCLUSION:Endoscopic salvage following dCRT is feasible and there is evidence, albeit of low quality, for the safety and efficacy of this approach in OSCC. Few studies have reported on endoscopic salvage for OAC. Prospective data are required to evaluate survival outcomes, adverse events and health related quality of life associated with salvage endoscopic procedures in OAC and OSCC, and to confirm the optimal endoscopic treatment approach for both subtypes.
AIM:This clinical investigation evaluated the efficacy and safety of the immune checkpoint inhibitor camrelizumab administered with concurrent chemoradiotherapy in patients with locally advanced cervical cancer. MATERIALS AND METHODS:This prospective trial enrolled patients aged 18-75 years with previously untreated cervical cancer classified as stage IIB to IVA according to the 2018 International Federation of Gynecology and Obstetrics system. Patients received intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) external-beam radiotherapy combined with three-dimensional brachytherapy, cisplatin chemotherapy, and camrelizumab 200 mg every 3 weeks for up to 1 year. Progression-free survival (PFS) was the primary endpoint; overall survival (OS) was a secondary exploratory endpoint of interest. Secondary endpoints also included treatment safety. RESULTS:A total of 50 patients were enrolled between February 2021 and July 2022. The majority had International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC1r/IIIC2r (70.0%) disease. The median age was 50.2 years (range, 30-65), and the median follow-up duration was 46.3 months (range, 37.5-55.4 months). The median PFS was not reached, and the 36-month PFS rate was 84.0% (95 % confidence interval [CI]: 73.8-94.2 %) The 36-month OS rate was 100%, and the median OS was not reached. Exploratory subgroup analyses for PFS and OS based on PD-L1 status and FIGO 2018 stage demonstrated favorable survival outcomes across subgroups, with no statistically significant difference between the PD-L1 positive and negative subgroups (log-rank P > 0.05). Treatment-related adverse events occurred in 96% of patients, although grade 3 or higher events were infrequent (0-18.0%), most commonly hematologic toxicity and enteritis. Immune-related adverse events (irAEs) occurred in 92.0% (46/50) of patients, and grade 3 or higher immune-related events occurred in 4.0% (2/50), including one case of conjunctivitis (2.0%, 1/50) and one case of lateral rectus muscle paralysis (2.0%, 1/50). No treatment-related mortalities or cases of irreversible organ damage were observed. An exploratory analysis examining the association between the total EQD2 radiation dose (≥85 Gy vs <85 Gy) and key outcomes (PFS, OS, grade ≥3 toxicities) found no statistically significant associations, likely due to the small sample size. One patient did not complete the 12-cycle imaging assessment on time. CONCLUSION:In this exploratory phase II single-arm study, camrelizumab administered with concurrent chemoradiotherapy demonstrated promising long-term survival outcomes and manageable toxicities in patients with locally advanced cervical cancer, providing preliminary support for further investigation.
AIMS:Gender disparities in radiation oncology (RO) persist across career stages, with women underrepresented in leadership and academic positions despite constituting a growing share of the clinical workforce. This study provides the first systematic cross-sectional analysis of gender distribution in RO in Austria and Switzerland, with descriptive data from South Tyrol. MATERIALS AND METHODS:For Austria (n = 231), an institutional census was conducted with approval by the Austrian Society of Radiation Oncology (ÖGRO). For Switzerland (n = 309), data were compiled through internet research and the Swiss medical register. South Tyrolean data (n = 11) are presented descriptively only. Gender, professional role, and academic qualification were recorded. RESULTS:In Austria, women constituted 59.3% of the workforce (P = .005), with a female majority among specialists (63.8%, P = .003), falling to 42.9% at leading positions and 16.7% among full professors (P = .021). In Switzerland, women constituted 42.7% overall (P = .010), declining from residents (45.5%) to leading positions (31.4%, P = .028) and full professors (20.0%, P = .001). Analysis confirmed a significant decline across career stages in Austria (P = .003) and Switzerland (P = .007). In South Tyrol, 81.8% were women, with all specialist positions held by women and both leadership positions held by men. CONCLUSION:Despite differences in overall workforce composition, a consistent leaky pipeline was identified across all three regions, with the most pronounced disparities at leadership and academic levels. These findings support the system-independent nature of gender inequity in RO, establishing a baseline for tracking progress toward parity across the German-speaking region.
AIMS:Chemoradiotherapy (CRT) followed by durvalumab is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). Radiation-induced lymphopenia (RIL) may impair anti-tumor immunity and reduce immunotherapy efficacy. This study evaluated circulating lymphocyte kinetics in relation to dosimetric parameters and their impact on survival. MATERIALS AND METHODS:We conducted a multicenter retrospective study across three hospitals. Patients had unresectable stage III NSCLC and received CRT followed by durvalumab. Absolute lymphocyte counts (ALC) were collected at baseline, radiotherapy initiation and completion, and 6-and 12 months postradiotherapy. RIL was graded using CTCAE V5.0. Tumoral, nodal, and total planning target volumes (PTV) and lung and heart dosimetric parameters were analyzed. Survival was assessed using landmark analysis. RESULTS:Seventy-six patients were included. All patients developed lymphopenia, with severe (grade ≥3) lymphopenia occurring in 51% (n = 39/76). Median ALC nadir was 490/mm3 at 45 days from radiotherapy initiation. ALC remained reduced at 1 year (1249/mm3; ±586). Patients with severe RIL had lower baseline ALC (P = 0.03). Severe RIL was associated with larger nodal PTV (P = 0.001) and total PTV (P = 0.02). Lung volume receiving 5 Gy (V5) (P < 0.01) and nodal PTV (P < 0.01) independently predicted severe RIL. Total PTV > 335 cm3 and nodal PTV > 181 cm3 significantly increased the risk of severe RIL risk. CRT plus durvalumab toxicity was not associated with lymphopenia severity (P = 0.2). No differences in overall survival or progression-free survival were observed between patients with or without severe RIL. CONCLUSION:RIL is a frequent and prolonged toxicity associated with nodal PTV and lung V5. Optimizing radiotherapy dosimetry may help to preserve immune function.
