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Objectives: To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset. Patients and methods: Patients with biopsy‐confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014–2018; six centres), and from the high‐intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK‐based registries (2006–2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post‐salvage with discrimination (concordance index [C‐index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically‐reasonable risk threshold ranges of 0.14–0.52 and 0.26–0.36 were considered, corresponding to previously published pooled 2‐year recurrence‐free survival rates for salvage local treatments. Results: A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow‐ups, and 72/168 (43%) within 2 years. The C‐index was 0.65 (95% confidence interval 0.58–0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14–0.52 risk threshold range, and all of the 0.26–0.36 range. Conclusion: In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow‐up is recommended. [ABSTRACT FROM AUTHOR]

Focal therapy treats individual areas of tumour in non-metastatic prostate cancer in patients unsuitable for active surveillance. The aim of this work was to evaluate the cost-effectiveness of focal therapy versus prostatectomy and external beam radiotherapy (EBRT). A Markov cohort health state transition model with four health states (stable disease, local recurrence, metastatic disease and death) was created, evaluating costs and utilities over a 10-year time horizon for patients diagnosed with non-metastatic prostate cancer. National Health Service (NHS) for England perspective was used, based on direct healthcare costs. Clinical transition probabilities were derived from prostate cancer registries in patients undergoing radical prostatectomy, EBRT and focal therapy using cryotherapy (Boston Scientific) or high-intensity focused ultrasound (HIFU) (Sonablate). Propensity score matching was used to ensure that at-risk populations were comparable. Variables included age, prostate-specific antigen (PSA), International Society of Urological Pathology (ISUP) grade group, maximum cancer core length (mm), T-stage and year of treatment. Focal therapy was associated with a lower overall cost and higher quality-adjusted life year (QALY) gains than either prostatectomy or EBRT, dominating both treatment strategies. Positive incremental net monetary benefit (NMB) values confirm focal therapy as cost-effective versus the alternatives at a willingness to pay (WTP) threshold of £30,000/QALY. One-way deterministic sensitivity analyses revealed consistent results. Data used to calculate the transition probabilities were derived from a limited number of hospitals meaning that other potential treatment options were excluded. Limited data were available on later outcomes and none on quality of life data, therefore, literature-based estimates were used. Cost-effectiveness modelling demonstrates use of focal therapy (cryotherapy or HIFU) is associated with greater QALY gains at a lower overall cost than either radical prostatectomy or EBRT, representing good value for money in the NHS. Focal therapy can be used for the primary treatment of individual areas of cancer in those patients with prostate cancer whose disease has not spread (localized or non-metastatic prostate cancer) and whose disease is unsuitable for active monitoring. Focal therapy in these patients results in similar control of the cancer to more invasive therapies, such as surgical removal of the prostate and radiotherapy, with the benefit of fewer sexual, urinary and rectal side effects. This work considered whether using focal therapy (either freezing the cancer cells using cryotherapy or using high-intensity focused ultrasound [HIFU] to destroy cancer cells) was good value for money in the National Health Service (NHS) compared with surgery or radiotherapy. An economic model was developed which considered the relative impact of treatment with focal therapies, surgery or radiotherapy within the NHS in England. Previously collected information from people undergoing treatment for their prostate cancer, together with published literature and clinical opinion, was used within the model to predict the treatment pathway, costs incurred and the results of treatment in terms of patient benefits (effectiveness and quality of life). The model showed that focal therapy using either cryotherapy or HIFU was associated with a lower overall cost and higher patient benefit than either surgery or radiotherapy, indicating that focal therapy represents good value for money in the NHS. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the oncological and functional outcomes of salvage cryosurgery (SCS) for radiorecurrent prostate cancer (rrPCa). Patients and Methods: A total of 169 consecutive patients with biopsy confirmed rrPCa were retrospectively analysed. All patients underwent SCS in a single referral centre between 2006 and 2018. The primary outcome was biochemical recurrence‐free survival (BRFS) according to the Phoenix definition (prostate‐specific antigen [PSA] nadir +2 ng/mL). The secondary outcomes were overall survival, BRFS defined as a PSA level of >0.5 ng/mL, metastasis‐free survival, androgen‐deprivation therapy (ADT)‐free survival, and functional outcomes. Complications were classified according to the Clavien–Dindo system. PSA was measured every 3–6 months postoperatively. Functional outcomes were scored as reported by patients at outpatient visits. Kaplan–Meier survival analysis and uni‐ and multivariable Cox regression were performed. Results: The median (interquartile range) follow‐up was 36 (18–66) months. The BRFS after 5 and 8 years was 52% (95% confidence interval [CI] 43–62%) and 45% (95% CI 35–57%), respectively. At multivariable analysis PSA level at initial diagnosis, initial treatment, interval between primary treatment and SCS, age at SCS, and post‐SCS PSA nadir were significant factors for BRFS. The 5‐year ADT‐free survival was 70% (95% CI 62–79%). Clavien–Dindo Grade ≥III complications occurred in 1.2% (two/169) of patients. In all, 19% (29/156) of patients had new‐onset urinary incontinence defined as >1 pad/24 h and 92% (57/62) of patients had new‐onset erectile dysfunction. Persistent urinary fistula occurred in 6.5% (11/169) of patients. Conclusions: The present study shows acceptable oncological outcomes of SCS considering the salvage character of the treatment. The occurrence of serious complications such as urinary incontinence and fistula should not be underestimated. [ABSTRACT FROM AUTHOR]

Purpose: Most patients with local prostate cancer recurrence after radiation therapy undergo palliative androgen deprivation therapy because whole-gland salvage treatments have a high risk of severe toxicity. Focal treatment reduces this risk while offering a second opportunity for cure. We report updated outcomes of ultrafocal salvage high-dose-rate brachytherapy (HDR-BT).Methods and Materials: Prospectively collected data from the first 50 treated patients were analyzed. Disease status was assessed by 3T multiparametric magnetic resonance imaging (MRI), 18F-Choline or 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography, and systematic or tumor-targeted biopsies. Ultrafocal salvage HDR-BT (1 × 19 Gy) was performed by implanting the clinical target volume (CTV: gross tumor volume + 5 mm margin) under fused transrectal ultrasound/MRI guidance. Follow-up included toxicity grading (using Common Terminology Criteria for Adverse Events 4.0), quality of life assessment, and prostate-specific antigen (PSA) testing.Results: Median follow-up was 31 months. Median CTV D95% was 18.8 Gy. We observed 2% grade 3 genitourinary toxicity, no grade 3 gastrointestinal toxicity, and 22% newly developed grade 3 erectile dysfunction. Five of 13 patients (38%) with self-reported pretreatment potency (International Index of Erectile Function >17) remained potent. Clinically relevant quality of life deterioration was reported for only 6 of 31 items and was not statistically significant. Biochemical failure (nadir + 2) occurred in 26 patients. Among intraprostatic recurrences, 73% were in field. After 2.5 years, biochemical disease-free survival was 51% (95% confidence interval, 37%-69%), metastases-free survival was 75% (64%-89%), androgen deprivation therapy-free survival was 90% (82%-99%), and overall survival was 98% (94%-100%). Presalvage PSA, CTV size, and stage ≥T3 were significantly associated with biochemical failure. Higher-risk patients (stage ≥T3, PSA ≥10, or PSA double time ≤9 months) had 25% biochemical disease-free survival at 2.5 years versus 71% for lower-risk patients.Conclusions: At this early stage, MRI-guided ultrafocal HDR-BT seems to be a safe salvage treatment option, with acceptable biochemical control in a well-selected group of patients and potential for effectively postponing androgen deprivation therapy. [ABSTRACT FROM AUTHOR]

Prior research underlined the importance of timely oncological care as longer waiting times from diagnosis to treatment may result in poorer survival outcomes. The aim of this study was to determine the impact of waiting time from diagnosis to treatment on overall survival (OS) in patients with cervical cancer treated with curative intent. Patients from a nationwide population-based cohort with newly diagnosed cervical cancer between 2010 and 2019 were studied. Patients who underwent surgery or (chemo)radiotherapy with curative intent were selected. Waiting time (i.e. interval between first pathologic confirmation and treatment) was modelled as continuous (i.e. linear per week), dichotomized (i.e. ≤8 versus >8 weeks), and polynomial (i.e. restricted cubic splines). The association with OS was examined using Cox regression analyses. Among 6895 patients with cervical cancer, 2755 treated with primary surgery and 1898 who received primary (chemo)radiotherapy were included. Mean waiting time was 8.5 (±4.2) weeks to surgery and 7.7 (±2.9) weeks to (chemo)radiotherapy. Adjusted for confounders, waiting time to surgery was not significantly associated with OS (continuous HR 0.97 [95%CI: 0.93–1.01], dichotomized HR 0.93 [95%CI: 0.68–1.27], polynomial HR not significant). Similarly, a longer waiting time to (chemo)radiotherapy was not significantly associated with poorer OS (continuous HR 0.97 [95%CI: 0.93–1.00], dichotomized HR 0.91 [95%CI: 0.75–1.09], polynomial HR not significant). This large population-based study demonstrates that a longer waiting time (of up to 12 weeks) from diagnosis to treatment in patients with cervical cancer treated with curatively intended surgery or (chemo)radiotherapy does not negatively impact survival. • Waiting times to cervical cancer treatment can vary (e.g. from varying logistical challenges or fertility preservation). • The impact of waiting time from diagnosis to treatment with curative intent on overall survival (OS) was studied. • This nationwide population-based study confirmed (and adjusted for) established prognostic factors impacting OS. • In 2755 patients treated with surgery, longer waiting time (of up to 12 weeks) was not significantly associated with OS. • In 1898 patients treated with (chemo)radiotherapy, longer waiting time was also not significantly associated with OS. [ABSTRACT FROM AUTHOR]

Objectives: Focal salvage HIFU is a feasible therapeutic option in some men who have recurrence after primary radiotherapy for prostate cancer. We aimed to determine if multi-parametric quantitative parameters, in addition to clinical factors, might have a role in independently predicting focal salvage HIFU outcomes.Methods: A retrospective registry analysis included 150 consecutive men who underwent focal salvage HIFU (Sonablate500) (2006-2015); 89 had mpMRI available. Metastatic disease was excluded by nodal assessment on pelvic MRI, a radioisotope bone-scan and/or choline or FDG PET/CT scan. All men had mpMRI and either transperineal template prostate mapping biopsy or targeted and systematic TRUS-biopsy. mpMRI included T2-weighted, diffusion-weighted and dynamic contrast-enhancement. Pre-HIFU quantitative mpMRI data was obtained using Horos DICOM Viewer v3.3.5 for general MRI parameters and IB DCE v2.0 plug-in. Progression-free survival (PFS) was defined by biochemical failure and/or positive localized or distant imaging results and/or positive biopsy and/or systemic therapy and/or metastases/prostate cancer-specific death. Potential predictors of PFS were analyzed by univariable and multivariable Cox-regression.Results: Median age at focal salvage HIFU was 71 years (interquartile range [IQR] 65-74.5) and median PSA pre-focal salvage treatment was 5.8ng/ml (3.8-8). Median follow-up was 35 months (23-47) and median time to failure was 15 months (7.8-24.3). D-Amico low, intermediate and high-risk disease was present in 1% (1/89), 40% (36/89) and 43% (38/89) prior to focal salvage HIFU (16% missing data). 56% (50/89) failed by the composite outcome. A total of 22 factors were evaluated on univariable and 8 factors on multivariable analysis. The following quantitative parameters were included: Ktrans, Kep, Ve, Vp, IS, rTTP and TTP. On univariable analysis, PSA, prostate volume at time of radiotherapy failure and Ve (median) value were predictors for failure. Ve represents extracellular fraction of the whole tissue volume. On multivariable analysis, only Ve (median) value remained as an independent predictor.Conclusions: One pharmacokinetic quantitative parameter based on DCE sequences seems to independently predict failure following focal salvage HIFU for radio-recurrent prostate cancer. This likely relates to the tumor microenvironment producing heat-sinks which counter the heating effect of HIFU. Further validation in larger datasets and evaluating mechanisms to reduce heat-sinks are required. [ABSTRACT FROM AUTHOR]

• More grade 4 lymphopenia in extended-CROSS compared with CROSS CRT. • Grade 4 lymphopenia was associated with a reduced overall survival. • The pretreatment prediction model demonstrated good external performance. • The model identifies patients at high-risk for grade 4 lymphopenia. • The model could identify patients eligible for lymphopenia-mitigating strategies. The incidence of grade 4 lymphopenia in patients treated with chemoradiotherapy (CRT) according to Chemoradiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) regimen is unclear. The primary aim was to determine the incidence of grade 4 lymphopenia during CROSS for esophageal cancer. Secondary aims were to externally validate a prediction model for grade 4 lymphopenia and compare overall survival between patients with and without grade 4 lymphopenia. Patients who underwent CRT for esophageal cancer between 2014 and 2019 were eligible for inclusion. Patients with a planned radiation dose of 41.4 Gy (CROSS) or 50.4 Gy ("extended-CROSS") and concurrent carboplatin and paclitaxel were included. The primary outcome was the incidence of grade 4 lymphopenia during CRT defined according to Common Terminology Criteria for Adverse Events version 5.0 (i.e. lymphocyte count nadir < 0.2 µL). The secondary outcome measures were the prediction model's external performance (i.e. discrimination and calibration). Overall survival for patients with versus without grade 4 lymphopenia was compared using Kaplan–Meier analysis. A total of 219 patients were included of whom 176 patients (80%) underwent CROSS and 43 patients (20%) extended-CROSS. The incidence of grade 4 lymphopenia was 11% in CROSS and 33% in extended-CROSS (p < 0.001). External discrimination yielded a c-statistic of 0.80 (95% confidence interval: 0.70–0.89). External calibration of the model was poor in CROSS but fair in extended-CROSS. Adjusted calibration using intercept correction (adjusted for the lower a-priori risk for grade 4 lymphopenia in CROSS) showed fair agreement between the observed and predicted risk for grade 4 lymphopenia. Median overall survival in patients with versus without grade 4 lymphopenia was 12.7 versus 42.5 months (p = 0.045). The incidence of grade 4 lymphopenia is significantly higher in esophageal cancer patients receiving extended-CROSS compared to those receiving CROSS. The prediction model demonstrated good external performance in the setting of the CROSS-regimen and could be used to identify patients at high-risk for grade 4 lymphopenia who might be eligible for lymphopenia–mitigating strategies. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiation therapy (SBRT) has become a widely adopted treatment for patients with oligometastatic disease, despite limited evidence of superiority. We compared pain response and quality of life (QoL) in patients with oligometastatic disease treated with conventionally fractionated 3-dimensional radiation therapy (3DCRT) or SBRT to bone metastases.Methods and Materials: We included patients with oligometastatic disease (≤5 lesions within ≤3 organs) treated within the prospective PRESENT cohort. Main outcomes were pain response, clinical local control, and QoL 2, 4, and 8 weeks and 3, 6, and 12 months after treatment. Pain response was assessed only in patients who reported pain at baseline and was defined according to international consensus criteria.Results: Of 131 patients with oligometastatic disease, 66 patients were treated with 3DCRT and 65 patients with SBRT. A pain response was achieved in 81% (3DCRT) versus 84% (SBRT) with a median duration of 23 weeks (range, 1-58) and 24 weeks (range, 0-50), respectively. Reirradiation was needed in 33% versus 5% of the patients, respectively. None of the QoL subscales were significantly different between both groups.Conclusions: In patients with oligometastatic disease, SBRT to bone metastases did not improve pain response or QoL compared with 3DCRT. Reirradiation was less often needed in the SBRT group. [ABSTRACT FROM AUTHOR]

Background Overall survival (OS) of patients with diffuse intrinsic pontine glioma (DIPG) is poor. The purpose of this study is to analyse benefit and toxicity of re-irradiation at first progression. Methods At first progression, 31 children with DIPG, aged 2–16 years, underwent re-irradiation (dose 19.8–30.0 Gy) alone (n = 16) or combined with systemic therapy (n = 15). At initial presentation, all patients had typical symptoms and characteristic MRI features of DIPG, or biopsy-proven high-grade glioma. An interval of ≥3 months after upfront radiotherapy was required before re-irradiation. Thirty-nine patients fulfilling the same criteria receiving radiotherapy at diagnosis, followed by best supportive care (n = 20) or systemic therapy (n = 19) at progression but no re-irradiation, were eligible for a matched-cohort analysis. Results Median OS for patients undergoing re-irradiation was 13.7 months. For a similar median progression-free survival after upfront radiotherapy (8.2 versus 7.7 months; P = .58), a significant benefit in median OS (13.7 versus 10.3 months; P = .04) was observed in favour of patients undergoing re-irradiation. Survival benefit of re-irradiation increased with a longer interval between end-of-radiotherapy and first progression (3–6 months: 4.0 versus 2.7; P < .01; 6–12 months: 6.4 versus 3.3; P = .04). Clinical improvement with re-irradiation was observed in 24/31 (77%) patients. No grade 4–5 toxicity was recorded. On multivariable analysis, interval to progression (corrected hazard ratio = .27–.54; P < .01) and re-irradiation (corrected hazard ratio = .18–.22; P < .01) remained prognostic for survival. A risk score (RS), comprising 5 categories, was developed to predict survival from first progression (ROC: .79). Median survival ranges from 1.0 month (RS-1) to 6.7 months (RS-5). Conclusions The majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability. [ABSTRACT FROM AUTHOR]