Delphi consensus on stereotactic ablative radiotherapy for oligometastatic and oligoprogressive renal cell carcinoma-a European Society for Radiotherapy and Oncology study endorsed by the European Association of Urology.

The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.

Treatment outcomes of stereotactic ablative body radiotherapy on oligometastases from colorectal cancer: early results of a single institution service evaluation.

Objective: Stereotactic ablative radiotherapy (SABR) has been suggested to be an effective non-invasive ablative therapy for oligometastases originated from colorectal cancer (CRC). This study aimed to report CRC oligometastases SABR treatment outcomes in terms of overall survival (OS), progression-free survival (PFS) and post-treatment toxicities. Methods: Treatment records of patients with CRC metachronous oligometastases who underwent SABR at a single institution between February 2015 and December 2018 were retrospectively reviewed. OS and PFS were calculated using Kaplan-Meier statistics and post-RT toxicity data was scored following CTCAE v. 4.0. Analysis of prognostic factors on OS and PFS was performed based on site of primary cancer, types of treatment to primary cancer, number of oligometastases, SABR treatment sites, intervals between treatment to primary cancer and SABR to oligometastases, biological equivalent dose, cumulative gross tumour volume and planning target volume. Results: 75 patients with 86 CRC metachronous oligometastases (including liver, lung, lymph nodes and bone) were included. The median age was 65.5 years (range 42.5-87.2) with a median follow-up of 23.8 months (range 3.1-46.5). The estimated median PFS was 14.6 months (95% CI 9.6-19.6). and estimated median OS was 33.3 months (95% CI 22.9-43.7). Majority of patients tolerated SABR well with the most common acute side-effects of Grade 1 fatigue. No Grade 3 or higher toxicities were reported at any time points.Only SABR treatment sites (p = 0.03) and cumulative volumes of planning target volume (p = 0.02) were found to be statistically significant independent predictors of PFS and OS respectively. Conclusion: This study showed modest PFS, OS, and post-treatment toxicity outcomes on SABR to metachronous oligometastases from CRC. It has highlighted that cumulative tumour volume may be a stronger prognostic factor of OS comparing to the number of metastases. Advances in knowledge: There are limited data published on the efficacy and post-treatment toxicity of CRC oligometastases SABR with adequate length of follow-up. Our retrospective study suggests that cumulative tumour volume may be a stronger prognostic factor of OS comparing to the number of oligometastases.

Reirradiation Options for Previously Irradiated Prostate cancer (RO-PIP): Feasibility study investigating toxicity outcomes following reirradiation with stereotactic body radiotherapy (SBRT) versus high-dose-rate brachytherapy (HDR-BT).

INTRODUCTION: Radiotherapy is the most common curative treatment for non-metastatic prostate cancer; however, up to 13% of patients will develop local recurrence within 10 years. Patients can undergo further and potentially curative treatment including salvage surgery, brachytherapy (BT), external beam radiotherapy, high-intensity focused ultrasound and cryotherapy. Systematic review shows that high-dose-rate (HDR) BT and stereotactic body radiotherapy (SBRT) have the best outcomes in terms of biochemical control and lowest side effects. The reirradiation options for previously irradiated prostate cancer (RO-PIP) trial aims to determine the feasibility of recruitment to a trial randomising patients to salvage HDR-BT or SBRT and provide prospective data on patient recorded toxicity outcomes that will inform a future phase III trial. METHODS AND ANALYSIS: The primary endpoint of the RO-PIP feasibility study is to evaluate the patient recruitment potential over 2 years to a trial randomising to either SBRT or HDR-BT for patients who develop local recurrence of prostate cancer following previous radiation therapy. The aim is to recruit 60 patients across 3 sites over 2 years and randomise 1:1 to SBRT or HDR-BT. Secondary objectives include recording clinician and patient-reported outcome measures to evaluate treatment-related toxicity. In addition, the study aims to identify potential imaging, genomic and proteomic biomarkers that are predictive of toxicity and outcome based on hypoxia status, a prognostic marker of prostate cancer. ETHICS AND DISSEMINATION: This study has been approved by the Yorkshire and The Humber-Bradford Leeds Research Ethics Committee (Reference: 21/YH/0305, IRAS: 297060, January 2022). The results will be presented in national and international conferences, published in peer-reviewed journals and will be communicated to relevant stakeholders. A plain English report will be shared with the study participants, patients' organisations and media. TRIAL REGISTRATION NUMBER: ISRCTN 12238218 (Amy Ackroyd NIHR CPMS Team).

High dose simultaneous integrated boost for node positive cervical cancer.

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.

Ultra-hypofractionated radiotherapy for low- and intermediate risk prostate cancer: High-dose-rate brachytherapy vs stereotactic ablative radiotherapy.

PURPOSE: To compare the biochemical control rates (BCRs), late gastrointestinal (GI) and genitourinary (GU) toxicities in patients with low- and intermediate risk prostate cancer (PCa) treated with high-dose-rate brachytherapy (HDR BT) of 19 Gy/1 fraction, 26 Gy/2 fractions, or stereotactic ablative radiotherapy (SABR) of 36.25 Gy/5 fractions. METHODS AND MATERIALS: Between August 2008 and December 2017, patients with low- and intermediate risk PCa who received single dose or 2-fraction HDR BT, or 5-fraction SABR at a single institution were included. BCR for the whole population and the individual treatment groups were calculated using the Phoenix definition. Post treatment GI and GU toxicities were evaluated according to the CTCAE v4.0 guidelines. RESULTS: 185 patients with low- and intermediate risk PCa were included in this study with a median follow up of 60.5 months. BCRs at 3 and 5 years were 95% and 85% for all patients. The 5-year BCRs were 69%, 95% and 92% for the 19 Gy/1 fraction, 26 Gy/2 fractions and 36.25 Gy/5 fractions groups respectively. The cumulative 5-year incidence rates of ≥grade 2 GI events in the 19 Gy/1fr, 26 Gy/2fr and 36.25 Gy/5fr groups were 0%, 2% and 4%, respectively. Incidence rates in those treated in the 5-fraction SABR arm were significantly higher (p < 0.05) than those treated in both HDR BT arms where no statistically significant difference between the two HDR BT groups was seen (p = 0.15). The cumulative 5-year incidence rates of ≥grade 2 GU events in the 19 Gy/1fr, 26 Gy/2fr and 36.25 Gy/5fr groups were 30%, 5% and 6%, respectively. No statistically significant difference was found between the 26 Gy/2fr and 36.25 Gy/5fr (p = 0.37) treatment arms but the incidence rate in the 26 Gy/2fr were significantly lower than those seen after 19 Gy/1fr (p < 0.05). CONCLUSIONS: 26 Gy/2 fractions HDR BT provided equivalent BCR with lower toxicity compared to 36.25 Gy/5 fractions SABR. Both 2-fraction HBR BT and 5-fraction SABR achieved better BCRs than single dose 19 Gy HDR BT. The two-fraction HDR BT schedule should be considered as an important comparator in future clinical trials.

An international Delphi consensus for pelvic stereotactic ablative radiotherapy re-irradiation.

INTRODUCTION: Stereotactic Ablative Radiotherapy (SABR) is increasingly used to treat metastatic oligorecurrence and locoregional recurrences but limited evidence/guidance exists in the setting of pelvic re-irradiation. An international Delphi study was performed to develop statements to guide practice regarding patient selection, pre-treatment investigations, treatment planning, delivery and cumulative organs at risk (OARs) constraints. MATERIALS AND METHODS: Forty-one radiation oncologists were invited to participate in three online surveys. In Round 1, information and opinion was sought regarding participants' practice. Guidance statements were developed using this information and in Round 2 participants were asked to indicate their level of agreement with each statement. Consensus was defined as ≥75% agreement. In Round 3, any statements without consensus were re-presented unmodified, alongside a summary of comments from Round 2. RESULTS: Twenty-three radiation oncologists participated in Round 1 and, of these, 21 (91%) and 22 (96%) completed Rounds 2 and 3 respectively. Twenty-nine of 44 statements (66%) achieved consensus in Round 2. The remaining 15 statements (34%) did not achieve further consensus in Round 3. Consensus was achieved for 10 of 17 statements (59%) regarding patient selection/pre-treatment investigations; 12 of 13 statements (92%) concerning treatment planning and delivery; and 7 of 14 statements (50%) relating to OARs. Lack of agreement remained regarding the minimum time interval between irradiation courses, the number/size of pelvic lesions that can be treated and the most appropriate cumulative OAR constraints. CONCLUSIONS: This study has established consensus, where possible, in areas of patient selection, pre-treatment investigations, treatment planning and delivery for pelvic SABR re-irradiation for metastatic oligorecurrence and locoregional recurrences. Further research into this technique is required, especially regarding aspects of practice where consensus was not achieved.

The implementation of an empty bladder filling protocol for localised prostate volumetric modulated arctherapy (VMAT): early results of a single institution service evaluation.

OBJECTIVE: To examine the impact of an empty bladder filling protocol on patients receiving radical RT for localised prostate cancer on post RT toxicity and biochemical progression free survival (bPFS). METHODS AND MATERIALS: Records of patients receiving radical external beam RT (EBRT) for localised prostate cancer with a full or empty bladder were reviewed. These included the bladder size on planning CT, daily online image guided RT (IGRT) setup data, treatment time and post treatment follow up data.These included bPFS, gastrointestinal(GI) and genitourinary(GU) toxicity scoring post RT using the CTCAE v4.0 scoring system. All patients included in the study were planned and treated under the same departmental clinical protocol with VMAT and daily online IGRT corrections. RESULTS: 90 patients were treated with 60 Gy in 20 fractions with a median follow up of 48 months. At 4 years bPFS in the empty bladder group was 100 and 98% in the full bladder group (p = 0.27). There were no statistically significant differences in cumulative ≥Grade 2GU (p = 0.10) and GI (p = 0.27) toxicity rates between the two bladder filling protocols. No statistically significant differences in the IGRT setup between the two groups of patients. Although the median treatment times per fraction were not statistically different between the two groups (p = 0.47), patients in the full bladder filling group were required to spend a longer time in the RT department per treatment session for bladder filling. CONCLUSION: An empty bladder filling protocol has non-inferior bPFS, GI and GU toxicities at 4 years in patients with localised prostate cancer using advanced RT techniques in comparison to a full bladder filling protocol. A longer follow up with a larger sample size is required to validate this approach. ADVANCES IN KNOWLEDGE: This study suggests that an empty bladder filling protocol can be used in external beam EBRT for localised prostate cancer with non-inferior treatment outcomes.

A pilot study on dosimetric and radiomics analysis of urethral strictures following HDR brachytherapy as monotherapy for localized prostate cancer.

OBJECTIVE: A cohort of high dose-rate (HDR) monotherapy patients was analyzed to (i) establish the frequency of non-malignant urethral stricture; (ii) explore the relation between stricture formation with the dose distribution along the length of the urethra, and MRI radiomics features of the prostate gland. METHODS: A retrospective review of treatment records of patients who received 19 Gy single fraction of HDR brachytherapy (BT) was carried out. A matched pair analysis used one control for each stricture case matched with pre-treatment International Prostate Symptom Score (IPSS) score, number of needles used and clinical target volume volume for each stricture case identified.For all data sets, pre-treatment T2 weighted MRI images were used to define regions of interests along the urethra and within the whole prostate gland. MRI textural radiomics features-energy, contrast and homogeneity were selected. Wilcoxon signed-rank test was performed to investigate significant differences in dosimetric parameters and MRI radiomics feature values between cases and controls. RESULTS: From Nov 2010 to July 2017, there were 178 patients treated with HDR BT delivering 19 Gy in a single dose. With a median follow-up of 28.2 months, a total of 5/178 (3%) strictures were identified.10 patients were included in the matched pair analysis. The urethral dosimetric parameters investigated were not statistically different between cases and controls (p > 0.05). With regards to MRI radiomics feature analysis, significant differences were found in contrast and homogeneity between cases and controls (p < 0.05). However, this did not apply to the energy feature (p = 0.28). CONCLUSION: In this matched pair analysis, no association between post-treatment stricture and urethral dosimetry was identified. Our study generated a preliminary clinical hypothesis suggesting that the MRI radiomics features of homogeneity and contrast of the prostate gland can potentially identify patients who develop strictures after HDR BT. Although the sample size is small, this warrants further validation in a larger patient cohort. ADVANCES IN KNOWLEDGE: Urethral stricture has been reported as a specific late effect with prostate HDR brachytherapy. Our study reported a relatively low stricture rate of 3% and no association between post-treatment stricture and urethral dosimetry was identified. MRI radiomics features can potentially identify patients who are more prone to develop strictures.

The impact of intra-fractional bladder filling on "Plan of the day" adaptive bladder radiotherapy.

A retrospective audit on the "Plan of the day" (POD) selection and intra-fractional bladder fillings were carried out on twenty adaptive bladder radiotherapy patients at a single institution. Treatment time, differences in bladder volume and displacement of outer bladder wall expansion over the treatment fraction were analysed. Average treatment time was 8.9 min. The mean percentage difference in bladder volume pre and post treatment was 13.7%, resulting in expansion of the bladder predominately in the superior and anterior directions. This audit confirmed that the institution's POD process sufficed without being significantly affected by the intra-fractional bladder filings.

Erratum to "The impact of intra-fractional bladder filling on ''Plan of the day" adaptive bladder radiotherapy" [Tech. Innov. Patient Supp. Radiat. Oncol. 9 (2019) 31-34].

[This corrects the article DOI: 10.1016/j.tipsro.2019.01.001.].

The impact of bladder preparation protocols on post treatment toxicity in radiotherapy for localised prostate cancer patients.

OBJECTIVE: This study compares the post radiotherapy related toxicity between the use of an empty and a full bladder preparation protocol in patients receiving radical radiotherapy for localised prostate cancer. METHODS AND MATERIALS: A retrospective review of patient treatment records in which they were treated with a standard radiotherapy schedule (60Gy/20 fractions) to prostates and base of seminal vesicles only and followed two different bladder preparation (empty and full) protocols was carried out. This included each patient's daily image guided radiotherapy (IGRT) setup, treatment time, bladder size on planning computed tomography, organs at risk dose volume histograms (OAR DVHs) and 12 months post treatment gastrointestinal (GI) and genitourinary (GU) toxicity data. RESULTS: 20 patients were included. There were significant differences in IGRT setup between the two groups. Although treatment times of the two groups were not significantly different, 5/200 (2.5%) sessions were longer than 20 min in the full bladder group while this was not found in the other group.Associations between bladder preparation protocols and GI (p = 1.0) and GU (p = 0.6) toxicities were not statistically significant. The bladder size on planning CT was not significantly correlated to the GI (R = 0.06, p = 0.8) or GU (R = 0.27, p = 0.3) toxicity scores. No significant differences were found in OAR DVHs between patients with and without GI and GU toxicities. No grade 3/4 toxicities were reported. CONCLUSION: The empty bladder preparation approach has non-inferior acute and intermediate post RT GI and GU toxicities in patients treated for localised prostate cancer with advanced radiotherapy techniques compared to the full bladder preparation.