P. Hoskin

Evaluation of brachytherapy applicators and their association with morbidity and local control in cervix cancer: An EMBRACE I analysis

To investigate the effects of brachytherapy (BT) applicator and implant type on morbidity and local control (LC) in locally advanced cervix cancer patients. 1071 patients treated with radiochemotherapy including MRI-guided BT using tandem&ring (T&R) or tandem&ovoids (T&O) from 19 EMBRACE-I centers were analyzed. Intracavitary (IC) or intracavitary/interstitial (IC/IS) implants were used. Centers came from different brachytherapy traditions and followed their institutional dose aims and planning strategies. LC and physician-assessed morbidity (median follow-up 48 months) was compared between applicator/implant types using Cox proportional hazard model adjusting for patient characteristics and treatment-related potential confounders. Moderate-to-severe (G ≥ 2) genito-urinary (cystitis/frequency/incontinence), gastro-intestinal (proctitis/bleeding/diarrhea) and vaginal (stenosis/mucositis) symptoms were analysed individually. Severe events (G ≥ 3) were pooled per organ. The T&O (n = 346) compared to T&R (n = 725) had a higher risk of morbidity, with HRs > 1.3 in 14/16 individual G ≥ 2 symptoms and in 3/4 G ≥ 3 pooled organ symptoms. Patients treated with IC/IS (n = 512) compared to IC (n = 559) were not at higher risk of G ≥ 2 symptoms, with HRs < 1 in 6/8 MVAs. Crude incidence of local failure was 7.3 % (25/343) for T&O and 6.6 % (47/712) for T&R. In this patient cohort, treated between 2008-2015, T&R and T&O demonstrated comparable LC. However, a higher risk of morbidity is reported for T&O. This increased risk was partly explained by hotspot doses, with factors such as irradiated volumes and organ irradiation length also contributing. Additionally, implant quality, dose planning aims and strategies, and morbidity reporting may have impacted the observed differences in morbidity. IC/IS applicators did not increase morbidity risk compared to IC applicators.

Development and refinement of patient care recommendations in brachytherapy for locally advanced cervical cancer using nominal group technique workshops

Abstract Purpose Patient experiences of brachytherapy for locally advanced cervical cancer (LACC) are widely variable, with reports of difficult and traumatic experiences and aspects of care requiring improvement. The aim of this study was to develop patient care recommendations and consult with key stakeholders to review, refine and prioritise recommendations. Methods Phase 1: Patient care recommendations were developed from qualitative exploratory study data. Phase 2: Service users and providers with recent experience of brachytherapy for LACC were recruited to online nominal group technique (NGT) workshops. Four NGT stages were followed: (1) initial voting and silent generation; (2) round robin; (3) clarification; and (4) prioritisation. Voting data were summed across the workshops, deriving inter-group scores. Qualitative data were analysed through content analysis. Results Phase 1: Fifty-one patient care recommendations were developed. Phase 2: Thirteen participants took part in three online NGT workshops, with a combination of service users and providers. Initial recommendations were voted on; four new recommendations were added; minor changes were made and second voting was undertaken. Recommendations were positively received with 25 recommendations scoring maximum points from all participants. An importance score above 90% was given to 46 recommendations. The remaining recommendations received scores between 74 and 90%. Conclusions NGT workshops facilitated collaboration between key stakeholders, discussing, refining and prioritising patient care recommendations, leading to verification of achievable and relevant recommendations. These provide a foundation for future development of guidelines and subsequent implementation into clinical practice, aiming to improve consistency of care and patient experiences of brachytherapy for LACC.

High dose simultaneous integrated boost for node positive cervical cancer

Abstract Introduction Lymph node metastases presenting with locally advanced cervical cancer are poor prognostic features. Modern radiotherapy approaches enable dose escalation to radiologically abnormal nodes. This study reports the results of a policy of a simultaneous integrated boost (SIB) in terms of treatment outcomes. Materials and methods Patients treated with radical chemoradiation with weekly cisplatin for locally advanced cervical cancer including an SIB to radiologically abnormal lymph nodes were analysed. All patients received a dose of 45 Gy in 25 fractions and a SIB dose of 60 Gy in 25 fractions using intensity modulated radiotherapy/volumetric modulated arc therapy, followed by high dose rate brachytherapy of 28 Gy in 4 fractions. A control cohort with radiologically negative lymph nodes was used to compare impact of the SIB in node positive patients. Treatment outcomes were measured by overall survival (OS), post treatment tumour response and toxicities. The tumour response was based on cross sectional imaging at 3 and 12 months and recorded as local recurrence free survival (LRFS), regional recurrence free survival (RRFS) and distant recurrence free survival (DRFS). Results In between January 2015 and June 2017, a total of 69 patients with a median follow up of 30.9 months (23 SIB patients and 46 control patients) were identified. The complete response rate at 3 months was 100% in the primary tumour and 83% in the nodal volume receiving SIB. The OS, LRFS, RRFS and DRFS at 3 years of the SIB cohort were 69%, 91%, 79% and 77% respectively. High doses can be delivered to regional pelvic lymph nodes using SIB without excessive toxicity. Conclusion Using a SIB, a total dose of 60 Gy in 25 fractions chemoradiation can be delivered to radiologically abnormal pelvic nodes with no increase in toxicity compared to node negative patients. The adverse impact of positive nodal status may be negated by high dose deposition using SIB, but larger prospective studies are required to confirm this observation.

Response to Yuce Sari et al.

Limitations and future directions in identifying risk factors for radiotherapy related pelvic insufficiency fractures in gynecological cancers: A scoping review

A systematic search of PubMed and EMBASE was conducted using terms such as "pelvic insufficiency fractures", "radiotherapy" and "gynecological cancers". Citations of relevant studies were also screened. Eligible studies included gynecolgical patients treated with pelvic RT, and reporting risk factors for RRIFs. Key data, including study characteristics, incidence rates, fracture definitions, imaging and dosimetry methods and statistical approaches were extracted. The Transparent Reporting of a multivariable prediction modelfor Individual Prognosis Or Diagnosis (TRIPOD) checklist was used to assess the methodological quality of the included studies. 28 studies met the inclusion criteria. RRIF incidence ranged from 1.7% to 37.4%. Commonly reported risk factors included advanced age, postmenopausal status, higher RT doses, low body weight, pre-existing osteoporosis, and concurrent chemotherapy. Imaging protocols, fracture definitions, and timing of detection varied widely. Statistical limitations, including reliance on univariable analyses, small sample sizes, and inconsistent baseline assessments, were common and limit reliable interpretation of risk factors. Anatomical targets for dose evaluation varied, with few studies correcting for biologically effective dose. Only one study developed a predictive model for RRIFs, which demonstrated moderate performance but lacked validation. Bone health assessments were inconsistently performed. Interdisciplinary approaches to improve fracture risk prediction, reduce treatment-related toxicity, and guide clinical decision-making.

Quantifying the dosimetric impact of online daily adaptation for MR-guided RT in cervical cancer

Purpose: This study assessed the inter- and intra-fractional dosimetric impact of MR-Linac-based adaptive radiotherapy for cervical cancer (CC). Methods: A retrospective analysis of five node-negative, locally advanced cervical cancer patients treated under the MOMENTUM study (NCT04075305) using adapt-to-shape (ATS) on an Elekta Unity MR-Linac. Assessing the dosimetric impact of daily online adaptations: (1) comparing dose between daily adapted (MR-adapted) and non-adapted (MR-guided) plans, by quantifying dose differences relative to reference plans (by 2 and 5%) and evaluating adaptation frequency; (2) performing intra-fraction dose evaluations. Dose metrics for targets and organs at risk (OARs) were evaluated following EMBRACE II guidelines. Results: MR-adapted plans improved target coverage or reduced OAR dose in 82–100% of fractions at a 2% dose deviation (and in 25–84% at a 5% deviation), compared to MR-guided plans. Dose reductions for OARs ranged from 2 to 8% for D0.1%, 4.77–16.70% for V4000cGy and 2.10–14.00% for V3000cGy. Intra-fraction analysis showed that the difference between daily planned and delivered doses in all target structures was not clinically significant, ranging from 0.08 to 2.20%, except two fractions that experienced higher deviations (5%) in ITV45. Treatment was well-tolerated, with no Grade 2 or 3 toxicities reported. Interpretation: MR-guided plans required adaptation in 25–100% of the fractions when compared to MR-adapted plans. MR-adapted plans demonstrated enhanced target dose consistency and reduced OAR dose for all patients, highlighting the benefits of daily adaptation. Despite longer treatment times, dose accuracy was preserved. Toxicity results for MRgART in CC appear promising.

The Current use of Adaptive Strategies for External Beam Radiotherapy in Cervical Cancer: A Systematic Review

Variability in the target and organs at risk (OARs) in cervical cancer treatment presents challenges for precise radiotherapy. Adaptive radiotherapy (ART) offers the potential to enhance treatment precision and outcomes. However, the increased workload and a lack of consensus on the most suitable ART approach hinder its clinical adoption. This systematic review aims to assess the current use of adaptive strategies for cervical cancer and define the optimal approach. A systematic review of current literature published between January 2012 and May 2023 was conducted. Searches used PubMed/Medline, Cochrane Library, and Web of Science databases, supplemented with the University of Manchester, Google Scholar, and papers retrieved from reference lists. The review assessed workflows, compared dosimetric benefits, and examined resources for each identified strategy. Excluded were abstracts, conference abstracts, reviews, articles unrelated to ART management, proton therapy, brachytherapy, or qualitative studies. A narrative synthesis involved data tabulation, summarizing selected studies detailing workflow for cervical cancer and dosimetric outcomes for targets and OARs. Sixteen articles met the inclusion criteria; these were mostly retrospective simulation planning studies, except four studies that had been clinically implemented. We identified five approaches for ART radiotherapy for cervical cancer: reactive and scheduled adaptation, internal target volume (ITV)-based approach using library of plans (LOP), fixed-margin approach using LOP, and real-time adaptation, with each approach reducing irradiated volumes without compromising target coverage compared to the non-ART approach. The LOP-based ITV approach is the most used and clinically assessed. Identifying the optimal strategy is challenging due to dosimetric assessment limitations. Implementing cervical cancer ART necessitates strategic optimization of clinical benefits and resources through research, including studies to identify the optimal frequency, and prospective evaluations of toxicity.