AAPM Task Group Report 267: A joint AAPM GEC-ESTRO report on biophysical models and tools for the planning and evaluation of brachytherapy.

Brachytherapy utilizes a multitude of radioactive sources and treatment techniques that often exhibit widely different spatial and temporal dose delivery patterns. Biophysical models, capable of modeling the key interacting effects of dose delivery patterns with the underlying cellular processes of the irradiated tissues, can be a potentially useful tool for elucidating the radiobiological effects of complex brachytherapy dose delivery patterns and for comparing their relative clinical effectiveness. While the biophysical models have been used largely in research settings by experts, it has also been used increasingly by clinical medical physicists over the last two decades. A good understanding of the potentials and limitations of the biophysical models and their intended use is critically important in the widespread use of these models. To facilitate meaningful and consistent use of biophysical models in brachytherapy, Task Group 267 (TG-267) was formed jointly with the American Association of Physics in Medicine (AAPM) and The Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO) to review the existing biophysical models, model parameters, and their use in selected brachytherapy modalities and to develop practice guidelines for clinical medical physicists regarding the selection, use, and interpretation of biophysical models. The report provides an overview of the clinical background and the rationale for the development of biophysical models in radiation oncology and, particularly, in brachytherapy; a summary of the results of literature review of the existing biophysical models that have been used in brachytherapy; a focused discussion of the applications of relevant biophysical models for five selected brachytherapy modalities; and the task group recommendations on the use, reporting, and implementation of biophysical models for brachytherapy treatment planning and evaluation. The report concludes with discussions on the challenges and opportunities in using biophysical models for brachytherapy and with an outlook for future developments.

Capivasertib in combination with enzalutamide for metastatic castration resistant prostate cancer after docetaxel and abiraterone: Results from the randomized phase II RE-AKT trial.

BACKGROUND: PTEN loss and aberrations in PI3K/AKT signaling kinases associate with poorer response to abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC). In this study, we assessed antitumor activity of the AKT inhibitor capivasertib combined with enzalutamide in mCRPC with prior progression on AA and docetaxel. METHODS: This double-blind, placebo-controlled, randomized phase 2 trial, recruited men ≥ 18 years with progressing mCRPC and performance status 0-2 from 15 UK centers. Randomized participants (1:1) received enzalutamide (160 mg orally, once daily) with capivasertib (400 mg)/ placebo orally, twice daily on an intermittent (4 days on, 3 days off) schedule. Primary endpoint was composite response rate (RR): RECIST 1.1 objective response, ≥ 50 % PSA decrease from baseline, or circulating tumor cell count conversion (from ≥ 5 at baseline to < 5 cells/7.5 mL). Subgroup analyses by PTENIHC status were pre-planned. RESULTS: Overall, 100 participants were randomized (50:50); 95 were evaluable for primary endpoint (47:48); median follow-up was 43 months. RR were 9/47 (19.1 %) enzalutamide/capivasertib and 9/48 (18.8 %) enzalutamide/placebo (absolute difference 0.4 % 90 %CI -12.8 to 13.6, p = 0.58), with similar results in the PTENIHC loss subgroup. Irrespective of treatment, OS was significantly worse for PTENIHC loss (10.1 months [95 %CI: 4.6-13.9] vs 14.8 months [95 %CI: 10.8-18]; p = 0.02). Most common treatment-emergent grade ≥ 3 adverse events for the combination were diarrhea (13 % vs 2 %) and fatigue (10 % vs 6 %). CONCLUSIONS: Combined capivasertib/enzalutamide was well tolerated but didn't significantly improve outcomes from abiraterone pre-treated mCRPC.

Quality-of-life outcomes in metastatic spinal cord compression: findings from the SCORAD trial.

PURPOSE: This article reports detailed quality-of-life data including preferred and actual place of care from SCORAD, the only large prospective randomized trial in metastatic spinal cord compression (MSCC). METHODS: SCORAD compared 2 doses of radiotherapy in patients with MSCC: 8 Gy single fraction and 20 Gy in 5 fractions. In total, 686 patients were randomized, of whom 590 had Health-Related Quality of Life (HRQoL) data collected at baseline and at least 1 later time point. HRQoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 supplemented with the QLU-C10D and data on place of care at weeks 1, 4, 8, and 12 postrandomization. Quality-of-Life Adjusted Survival was computed by multiplying Kaplan-Meier survival probabilities with the UK utility weights obtained from the QLU-C10D. RESULTS: Patients with a baseline physical functioning score of above 50 demonstrated a 28% reduction in the risk of death (hazard ratio [HR] = 0.72, 99% confidence interval [CI] = 0.54 to 0.95; P = .003). An increased risk of death was associated with fatigue (HR = 1.35, 99% CI = 1.03 to 1.76; P = .0040), dyspnea (HR = 1.61, 99% CI = 1.24 to 2.08; P < .001), and appetite loss (HR = 1.25, 99% CI = 0.99 to 1.59; P = .014). The preferred place of care for the majority was at home or with relatives (61%-74% across the 12 weeks) but achieved by only 53% at 8 weeks. CONCLUSIONS: Prolonged survival in patients with MSCC was associated with better HRQoL. More than 60% of patients preferred to be cared for at home or with relatives, but only half were able to achieve this. There was no difference in HRQoL between the multifraction and single-fraction groups. TRIAL REGISTRATION: ISRCTN97555949 and ISRCTN97108008.

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial.

BACKGROUND: Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. METHODS: RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. INTERPRETATION: Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.

Exploratory study of using Magnetic resonance Prognostic Imaging markers for Radiotherapy In Cervix cancer (EMPIRIC): a prospective cohort study protocol.

INTRODUCTION: Radical chemoradiotherapy represents the gold standard for locally advanced cervical cancer. However, despite significant progress in improving local tumour control, distant relapse continues to impact overall survival. The development of predictive and prognostic biomarkers is consequently important to risk-stratify patients and identify populations at higher risk of poorer treatment response and survival outcomes. Exploratory study of using Magnetic resonance Prognostic Imaging markers for Radiotherapy In Cervix cancer (EMPIRIC) is a prospective exploratory cohort study, which aims to investigate the role of multiparametric functional MRI (fMRI) using diffusion-weighed imaging (DWI), dynamic contrast-enhanced (DCE) and blood oxygen level-dependent imaging (BOLD) MRI to assess treatment response and predict outcomes in patients undergoing radical chemoradiotherapy for cervical cancer. METHODS AND ANALYSIS: The study aims to recruit 40 patients across a single-centre over 2 years. Patients undergo multiparametric fMRI (DWI, DCE and BOLD-MRI) at three time points: before, during and at the completion of external beam radiotherapy. Tissue and liquid biopsies are collected at diagnosis and post-treatment to identify potential biomarker correlates against fMRI. The primary outcome is to evaluate sensitivity and specificity of quantitative parameters derived from fMRI as predictors of progression-free survival at 2 years following radical chemoradiotherapy for cervical cancer. The secondary outcome is to investigate the roles of fMRI as predictors of overall survival at 2 years and tumour volume reduction across treatment. Statistical analyses using regression models and survival analyses are employed to evaluate the relationships between the derived parameters, treatment response and clinical outcomes. ETHICS AND DISSEMINATION: The EMPIRIC study received ethical approval from the NHS Health Research Authority (HRA) on 14 February 2022 (protocol number RD2021-29). Confidentiality and data protection measures are strictly adhered to throughout the study. The findings of this study will be disseminated through peer-reviewed publications and scientific conferences, aiming to contribute to the growing body of evidence on the use of multiparametric MRI in cervical cancer management. TRIAL REGISTRATION NUMBER: NCT05532930.

Beyond surgery: bladder preservation and the role of systemic treatment in localised muscle-invasive bladder cancer.

Over the last two to three decades the non-surgical curative management of bladder cancer has significantly progressed. Increasing evidence supports the use of bladder preservation as an alternative to radical cystectomy (RC) for localised muscle-invasive bladder cancer (MIBC). Radiosensitisation with chemotherapy or hypoxia modification improves the efficacy of radiotherapy. Systemic treatments play an important role in the management of localised MIBC with the benefit of neoadjuvant chemotherapy prior to radical treatment well established. The use of immune checkpoint inhibitors (ICIs) in the radical treatment of bladder cancer, their safe combination with radical radiotherapy regimens and whether the addition of ICIs improve rates of cure are outstanding questions beginning to be answered by ongoing clinical trials. In this narrative review, we discuss the current evidence for bladder preservation and the role of systemic treatments for localised MIBC.

Brachytherapy for rhabdomyosarcoma: Survey of international clinical practice and development of guidelines.

BACKGROUND AND PURPOSE: The purpose of this study was to address the lack of published data on the use of brachytherapy in pediatric rhabdomyosarcoma by describing current practice as starting point to develop consensus guidelines. MATERIALS AND METHODS: An international expert panel on the treatment of pediatric rhabdomyosarcoma comprising 24 (pediatric) radiation oncologists, brachytherapists and pediatric surgeons met for a Brachytherapy Workshop hosted by the European paediatric Soft tissue Sarcoma Study Group (EpSSG). The panel's clinical experience, the results of a previously distributed questionnaire, and a review of the literature were presented. RESULTS: The survey indicated the most common use of brachytherapy to be in combination with tumor resection, followed by brachytherapy as sole local therapy modality. HDR was increasingly deployed in pediatric practice, especially for genitourinary sites. Brachytherapy planning was mostly by 3D imaging based on CT. Recommendations for patient selection, treatment requirements, implant technique, delineation, dose prescription, dose reporting and clinical management were defined. CONCLUSIONS: Consensus guidelines for the use of brachytherapy in pediatric rhabdomyosarcoma have been developed through multicenter collaboration establishing the basis for future work. These have been adopted for the open EpSSG overarching study for children and adults with Frontline and Relapsed RhabdoMyoSarcoma (FaR-RMS).

Radiotherapy trial quality assurance processes: a systematic review.

Quality assurance remains a neglected component of many trials, particularly for technical interventions, such as surgery and radiotherapy, for which quality of treatment is an important component in defining outcomes. We aimed to evaluate evidence for the processes used in radiotherapy quality assurance of clinical trials. A systematic review was undertaken focusing on use of a pre-trial outlining benchmark case and subsequent on-trial individual case reviews of outlining for recruited patients. These pre-trial and on-trial checks are used to ensure consistency and standardisation of treatment for each patient recruited to the trial by confirming protocol compliance. Non-adherence to the trial protocol has been shown to have a negative effect on trial outcomes. 29 studies published between January, 2000, and December, 2022, were identified that reported on either outlining benchmark case results or outlining individual case review results, or both. The trials identified varied in their use of radiotherapy quality assurance practices and reporting of outcomes was inconsistent. Deviations from trial protocols were frequent, particularly regarding outlining. Studies correlating benchmark case results with on-trial individual case reviews provided mixed results, meaning firm conclusions could not be drawn regarding the influence of the pre-trial benchmark case on subsequent on-trial performance. The optimal radiotherapy quality assurance processes were unclear, and there was little evidence available. Improved reporting of outcomes from radiotherapy quality assurance programmes is needed to develop an evidence base for the optimal approach to radiotherapy quality assurance in trials.

Tumour response to hypoxia: understanding the hypoxic tumour microenvironment to improve treatment outcome in solid tumours.

Hypoxia is a common feature of solid tumours affecting their biology and response to therapy. One of the main transcription factors activated by hypoxia is hypoxia-inducible factor (HIF), which regulates the expression of genes involved in various aspects of tumourigenesis including proliferative capacity, angiogenesis, immune evasion, metabolic reprogramming, extracellular matrix (ECM) remodelling, and cell migration. This can negatively impact patient outcomes by inducing therapeutic resistance. The importance of hypoxia is clearly demonstrated by continued research into finding clinically relevant hypoxia biomarkers, and hypoxia-targeting therapies. One of the problems is the lack of clinically applicable methods of hypoxia detection, and lack of standardisation. Additionally, a lot of the methods of detecting hypoxia do not take into consideration the complexity of the hypoxic tumour microenvironment (TME). Therefore, this needs further elucidation as approximately 50% of solid tumours are hypoxic. The ECM is important component of the hypoxic TME, and is developed by both cancer associated fibroblasts (CAFs) and tumour cells. However, it is important to distinguish the different roles to develop both biomarkers and novel compounds. Fibronectin (FN), collagen (COL) and hyaluronic acid (HA) are important components of the ECM that create ECM fibres. These fibres are crosslinked by specific enzymes including lysyl oxidase (LOX) which regulates the stiffness of tumours and induces fibrosis. This is partially regulated by HIFs. The review highlights the importance of understanding the role of matrix stiffness in different solid tumours as current data shows contradictory results on the impact on therapeutic resistance. The review also indicates that further research is needed into identifying different CAF subtypes and their exact roles; with some showing pro-tumorigenic capacity and others having anti-tumorigenic roles. This has made it difficult to fully elucidate the role of CAFs within the TME. However, it is clear that this is an important area of research that requires unravelling as current strategies to target CAFs have resulted in worsened prognosis. The role of immune cells within the tumour microenvironment is also discussed as hypoxia has been associated with modulating immune cells to create an anti-tumorigenic environment. Which has led to the development of immunotherapies including PD-L1. These hypoxia-induced changes can confer resistance to conventional therapies, such as chemotherapy, radiotherapy, and immunotherapy. This review summarizes the current knowledge on the impact of hypoxia on the TME and its implications for therapy resistance. It also discusses the potential of hypoxia biomarkers as prognostic and predictive indictors of treatment response, as well as the challenges and opportunities of targeting hypoxia in clinical trials.

A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial.

BACKGROUND: BC2001 showed combining chemotherapy (5-FU + mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. METHODS: RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). PRIMARY ENDPOINT: invasive loco-regional control (ILRC); secondary overall survival. FINDINGS: Hypoxia affected overall survival (HR = 1.30; 95% CI 0.99-1.70; p = 0.062): more uncertainty for ILRC (HR = 1.29; 95% CI 0.82-2.03; p = 0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n = 90, HR 1.69; 95% CI 0.99-2.89 p = 0.057) but not conventional (n = 207, HR 0.70; 95% CI 0.28-1.80, p = 0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n = 51; HR 14.2; 95% CI 1.7-119; p = 0.015) but not conventional (n = 24, HR 1.04; 95% CI 0.07-15.5, p = 0.978) radiotherapy. INTERPRETATION: Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial. FUNDING: Cancer Research UK, NIHR, MRC.

Radiotherapy in metastatic bladder cancer.

PURPOSE: To review available and emerging evidence of radiotherapy for symptom management and disease control in metastatic bladder cancer. METHODS: A literature search and subsequent cross-referencing were carried out for articles in the PubMed and Scopus databases using terms 'radiotherapy' OR 'palliative radiation therapy' with 'metastatic bladder cancer' OR 'advanced bladder cancer' between 1990 and 2023, excluding articles with no English translation. RESULTS: Palliative radiotherapy is an effective and accessible treatment for the alleviation of haematuria and pain due to the primary and metastatic disease. With growing recognition of oligometastatic disease state at diagnosis, response, or progression, radiotherapy can consolidate response by ablating residual or resistant lesions. Experience with other primary cancers supports positive impact of radiotherapy on disease control, quality of life, and survival in oligometastatic stage, without significant adverse effects. Alongside immune checkpoint inhibitors, fibroblast growth receptor inhibitors, and antibody-drug conjugates, the immunomodulatory potential of radiotherapy is being explored in combination with these systemic therapies for metastatic bladder cancer. CONCLUSION: Radiotherapy is an effective, safe, and accessible treatment modality for palliation as well as disease control in various clinical settings of metastatic bladder cancer. Its role in oligometastatic stage in combination with systemic therapy is expected to expand with emerging evidence.

Timing of High-Dose-Rate Brachytherapy With External Beam Radiation Therapy in Patients With Intermediate- and High-Risk Localized Prostate Cancer and Its Effects on Toxicity and Quality of Life: A Randomized Controlled Trial (THEPCA).

PURPOSE: High-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) are effective treatments for prostate cancer but cause genitourinary (GU) and gastrointestinal (GI) toxicities. There is no consensus on the timing of HDR-BT in relation to EBRT and the effect of sequencing on patients. The primary objective was to assess differences, if any, in the incidence of grade (G) 3 or higher GU toxicities from treatment. We also aimed to explore the incidence of G1 to G4 GI toxicities, quality of life (QOL), and patient satisfaction. Suppression of prostate-specific antigen (PSA) and signals for survival differences were also analyzed. METHODS AND MATERIALS: This was a single-center randomized trial in patients with intermediate- and high-risk localized prostate cancer who received HDR-BT before (Arm A) or after (Arm B) EBRT. Toxicities were graded using Common Terminology Criteria for Adverse Events (CTCAE). The International Prostate Symptom Score (IPSS) was used to assess lower urinary tract symptoms. The International Index of Erectile Function scale (IIEF) and Functional Assessment of Cancer Therapy-Prostate (FACT-P) were used to assess erectile dysfunction and QOL at 0, 3, 9, and 12 months. RESULTS: Fifty patients were recruited to each arm, with 48 and 46 patients completing treatment and follow-up in each arm, 81.5% of whom had high-risk disease. There were no G3 or G4 GU or GI toxicities. G1 urinary frequency was the most common adverse event experienced in both arms, peaking in incidence 3 months after treatment commenced (45.7% and 42.2% in Arm A and B, respectively). Up to 11% of patients reported G1 urinary frequency at 12 months. Other G1 GU toxicities experienced by >10% of patients were urinary tract obstruction, tract pain, and urgency. These symptoms also peaked in incidence at 3 months. G2 GU toxicities were uncommon and experienced in a maximum of 2 patients within each arm at any time point. Over 30% of patients had G1 flatulence at baseline, and this remained the most frequently occurring G1 GI toxicity throughout the study, peaking at 12 months (21.4% and 25.6% in Arm A and B, respectively). Other GI toxicities experienced by more than 10% of patients were GI pain, proctitis, and rectal mucositis, most of which demonstrated a peak incidence at 3 or 9 months. G2 GI toxicities were uncommon except for G2 flatulence. No significant difference was found in CTCAE, IPSS, IIEF, FACT-P, and QOL scores between the arms. Median prostate-specific antigen (PSA) follow-up was 5 years. Seven patients had treatment failure in each arm. Disease Free Survival (DFS) was 93.3% and 90.7% at 5 years in Arm A and B, respectively, with median failure time of 60 and 48 months in Arm A and B, respectively. There were no statistically significant differences between arms. CONCLUSIONS: The sequencing of HDR-BT and EBRT did not affect the incidence of G3 or G4 toxicities, and no significant differences were seen in other patient-reported outcomes. Treatment was well tolerated with maintained QOL scores. Treatment failure was low in both arms in a high-risk cohort; however, a larger study with longer follow-up is underway to establish whether the difference in median time to failure between the 2 arms is a signal of superiority.

Patient Experiences of Brachytherapy for Locally Advanced Cervical Cancer: Hearing the Patient Voice Through Qualitative Interviews.

PURPOSE: Brachytherapy for gynecological cancer is reported to cause pain, anxiety, and distress with no clear guidance for optimizing patient experiences. The aim of this study was to explore patient experiences of brachytherapy and views on improvement. METHODS AND MATERIALS: Semistructured interviews were undertaken with patients who had received brachytherapy for locally advanced cervical cancer. Two cohorts were recruited: cohort 1 had recently had brachytherapy, and cohort 2 was a year post brachytherapy. Four recruitment sites were selected, where brachytherapy is given in different ways, some with short day case procedures and others having 1 or 2 overnight stays with applicators in place. Consecutive patients were invited to interview. Participants were asked to retell their brachytherapy story, with views on their care and ideas for improvement. Interviews were audio recorded, transcribed, and data analyzed following Braun and Clarke's method for reflexive thematic analysis. RESULTS: Thirty-five interviews were conducted (20 in cohort 1 and 15 in cohort 2). Participant's ages ranged from 28 to 87 years. The interview duration ranged from 22 to 78 minutes. Difficult and traumatic experiences were reported, including periods of severe pain and perceptions of poor care. However, some participants described positive experiences and what went well. Three themes were developed: (1) how the patient got through it, (2) unpleasantness, discomfort, and the aftermath, and (3) emotional consequences and trauma. Some aspects of medium and long duration brachytherapy were found to be more problematic compared with short duration brachytherapy. Exploring experiences at 1-year post brachytherapy has provided insights into the long-lasting impact of brachytherapy experiences. CONCLUSIONS: Hearing the patient voice has demonstrated that further work is needed to improve patient care in modern brachytherapy techniques using different regimens and durations, to minimize difficult and traumatic patient experiences. Study insights will inform future work to develop clinical care recommendations.

ARCHERY: a prospective observational study of artificial intelligence-based radiotherapy treatment planning for cervical, head and neck and prostate cancer - study protocol.

INTRODUCTION: Fifty per cent of patients with cancer require radiotherapy during their disease course, however, only 10%-40% of patients in low-income and middle-income countries (LMICs) have access to it. A shortfall in specialised workforce has been identified as the most significant barrier to expanding radiotherapy capacity. Artificial intelligence (AI)-based software has been developed to automate both the delineation of anatomical target structures and the definition of the position, size and shape of the radiation beams. Proposed advantages include improved treatment accuracy, as well as a reduction in the time (from weeks to minutes) and human resources needed to deliver radiotherapy. METHODS: ARCHERY is a non-randomised prospective study to evaluate the quality and economic impact of AI-based automated radiotherapy treatment planning for cervical, head and neck, and prostate cancers, which are endemic in LMICs, and for which radiotherapy is the primary curative treatment modality. The sample size of 990 patients (330 for each cancer type) has been calculated based on an estimated 95% treatment plan acceptability rate. Time and cost savings will be analysed as secondary outcome measures using the time-driven activity-based costing model. The 48-month study will take place in six public sector cancer hospitals in India (n=2), Jordan (n=1), Malaysia (n=1) and South Africa (n=2) to support implementation of the software in LMICs. ETHICS AND DISSEMINATION: The study has received ethical approval from University College London (UCL) and each of the six study sites. If the study objectives are met, the AI-based software will be offered as a not-for-profit web service to public sector state hospitals in LMICs to support expansion of high quality radiotherapy capacity, improving access to and affordability of this key modality of cancer cure and control. Public and policy engagement plans will involve patients as key partners.