Oncology

Treatment and outcomes of patients with gastrointestinal toxicity following immunotherapy: A large multi-center retrospective study in the United Kingdom by the National Oncology Trainees Collaborative for Healthcare Research (NOTCH) (2022)

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Type of publication:
Conference abstract

Author(s):
Swaminathan M.; Angelakas A.; Baxter M.; Cotton J.; Dobeson C.B.; Feeney L.; Gault A.C.; Hughes D.J.; Jones C.; Lee R.; Mughal S.A.; *Parikh S.P.; Pritchard M.; Rodgers L.J.; Rowe M.P.; Salawu A.T.; Shotton R.; Tinsley N.; Tivey A.; Olsson-Brown A.C.;

Citation:
Immuno-Oncology and Technology. Conference: ESMO Immuno-Oncology Congress 2022. Geneva Switzerland. 16(Supplement 1) (no pagination), 2022. Article Number: 100230. Date of Publication: December 2022.

Abstract:
Background: Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of many cancers, but their use has been associated with the development of gastrointestinal (GI) toxicities such as colitis and hepatitis. Method(s): A multi-center retrospective study across 12 National Health Service centers across the United Kingdom (UK) was conducted by the UK National Oncology Trainees Collaborative for Healthcare Research (NOTCH) over a 2-year period. The study included patients receiving ICIs for malignant melanoma, non-small lung cancer and renal cell cancer as standard of care. Occurrence of clinically significant (>=grade 2) GI toxicity was assessed and correlated with subsequent treatment and outcomes. Multiple logistic regression was used to assess correlation. For overall survival (OS), Kaplan-Meier and log-rank tests were utilised. Result(s): The cohort included 2049 patients. 1230 (60%) were male with a median age of 66. Colitis occurred in 182 (8.9%) patients and hepatitis in 129 (6.3%). Of the patients where treatment was recorded, 129 (70.9%) received treatment with systemic steroids alone and 37 (20.3%) required second-line immunosuppressants (IS) in the colitis group. In the hepatitis group, 101 (78.3%) had steroids alone with 19 (14.7%) having IS. Improved OS was found in patients who experienced colitis (HR 2.59 95%CI: 2.15 to 3.11, p<0.0001) and hepatitis (HR 2.26, 95%CI: 1.84 to 2.79, p=<0.0001) compared to those with no adverse events. Pre-existing autoimmune disease (p=0.02) and combination ICIs (p=0.006) were predictors of colitis that required IS whilst grade 2 and 3 hepatitis (p<0.001) were predictors of hepatitis needing IS. The use of IS did not affect OS significantly in the colitis group (p=0.372) but did correlate with survival in the hepatitis group (p=0.037). Patients that were able to continue treatment with ICIs after toxicity had an increased OS in both groups (p<0.001). Conclusion(s): Patients with GI toxicity following treatment with ICIs have improved OS. The use of IS did not significantly affect OS which suggests they should continue to be utilised in the treatment of GI toxicity. Legal entity responsible for the study: United Kingdom National Oncology Trainees Collaborative for Healthcare Research (NOTCH).

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Effectiveness of weight loss interventions in breast cancer survivors: a systematic review of reviews (2022)

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Type of publication:Systematic Review

Author(s):*Lake B; Damery S; Jolly K

Citation:BMJ Open, 2022 Oct 07; Vol. 12 (10), pp. e062288

Abstract:Background: Elevated body mass index (BMI) in breast cancer survivors (BCS) is associated with cancer recurrence and poorer treatment response. Guidelines recommend 5%-10% weight loss for overweight or obese BCS.Objectives: To assess effectiveness of lifestyle interventions for female BCS on weight loss, BMI, body composition, health-related quality of life (HRQoL), physical functioning, psychosocial measures, biomarkers.Design: Systematic review of reviews and meta-analyses.Setting: All clinical settings.Participants: Adult female BCS (active treatment or post-treatment).Methods: Medline, Embase, CINAHL, PsycINFO, Cochrane Library (including Database of Abstracts of Reviews of Effects) were searched for systematic reviews published in English between 1990 and 2022, with weight, BMI or body fat as primary outcome. Narrative reviews, editorials, letters, conference abstracts were excluded. Review quality was assessed using the Joanna Briggs Institute quality assessment tool.Results: 17 reviews were included. Twelve reported significant reductions in one or more anthropometric outcomes: weight -1.36 kg (95% CI:-2.51 to -0.21) to -3.8 kg (95% CI: -5.6 to -1.9); BMI -0.89 kg/m 2 (95% CI: -0.15 to -0.28) to -3.59 kg/m 2 (95% CI: -6.29 to 0.89) or body fat -1.6% (95% CI: -2.31 to -0.88) to -2.6% (95% CI not reported). Significant reductions in two or more anthropometric outcomes were reported in 7/12 reviews, with effective interventions comprising aerobic exercise/aerobic exercise plus resistance training (n=5), or diet and exercise with or without counselling (n=2). Significant improvements were also reported for HRQoL (8/11 reviews), mental health (4/7) and physical functioning (2/3). Group interventions comprising aerobic exercise or aerobic exercise plus resistance training were most likely to improve outcomes.Conclusions: Lifestyle interventions can significantly improve outcomes for BCS. Multimodal interventions are likely to have the greatest impact in reducing weight, BMI and body fat. Further research must define the optimal combination, intensity and duration of effective interventions.

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Systematic Review of Focal and Salvage Cryotherapy for Prostate Cancer (2022)

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Type of publication:Systematic Review

Author(s):Chin YF; *Lynn N

Citation:Cureus, 2022 Jun 28; Vol. 14 (6), pp. e26400

Abstract:Cryotherapy is one of the recognised ablative modalities for both primary and salvage therapy for prostate cancer. It presents an alternative, less invasive treatment for an organ-confined disease, improved preservation of surrounding tissue and a more suitable option for patients who are unfit for radical prostatectomy. Nevertheless, the currently available literature is relatively too scarce to provide definite conclusions regarding the treatment outcomes in cryotherapy. The present study aimed to review current oncological and survival outcomes in cryotherapy for primary and recurrent prostate cancer. Furthermore, this study aimed to establish the complications and functional outcomes of cryotherapy for prostate cancer. A literature search was performed on the PubMed, Cochrane and Google Scholar databases. Current guidelines and recommendations from the European Association of Urology were also reviewed. The search keywords used included 'Cryotherapy, Prostate Cancer', 'Cryoablation, Prostate Cancer' and 'Cryosurgery, Focal Prostate Cancer'. Truncations and Boolean operators were used with the keywords. All relevant studies from after 2015, including abstracts and non-English research assessing oncological and functional outcomes and complications, were included. Twenty-six studies consisting of 11,228 patients were reviewed. Fifteen studies assessed the outcomes of primary cryotherapy, whereas 11 studies reported the outcomes in salvage therapy. The patient's age ranged 55-85 years, and the pre-procedural prostate-specific antigen (PSA) ranged 0.01-49.33 ng/mL. A total of 2031 patients were classified to be at low risk, 2,995 were at moderate risk and 253 were at high risk on the D'Amico prostate cancer risk classification system. Follow-ups ranged from 9.0 to 297.6 months. The disease-specific survival rate was 65.5%-100.0%, overall survival was 61.3%-99.1%, the PSA nadir was 0.01-2.63 ng/mL and the overall biochemical recurrence rate was 15.4%-62.0%. The complications included erectile dysfunction (3.7%-88.0%), urinary retention (2.13%-25.30%) and bladder neck stricture/stenosis (3.0%-16.7%). The functional assessment showed a mixture of improved, unchanged or worsened post-procedural outcomes in primary therapy. This systematic review did not find significant differences in the cancer-specific, overall and biochemical-free survival rate between the primary and salvage cryotherapy cohorts. The most common complications encountered in both cohorts were erectile dysfunction, urinary incontinence, lower urinary tract/bladder neck stricture and infection. More prospective and double-arm studies are critically needed to provide guidance on the careful selection of patient cohorts for cryotherapy, whether for curative or salvage intent.

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Quality of life and two-year results of a randomized phase III study of dysphagiaoptimized intensity modulated radiotherapy (DO-IMRT) versus standard IMRT (SIMRT) in head and neck cancer (2022)

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Type of publication:Conference abstract

Author(s):Nutting C.; Rooney K.; Foran B.; *Pettit L.; Beasley M.; Finneran L.; Roe J.; Tyler J.; Roques T.; Cook A.; Petkar I.; Bhide S.; Srinivasan D.; Boon C.; De Winton E.; Frogley R.; Sydenham M.A.; Emson M.; Hall E.

Citation:Journal of Clinical Oncology. Conference: Annual Meeting of the American Society of Clinical Oncology, ASCO 2022. Online. 40(16 Supplement 1) (no pagination), 2022. Date of Publication: June 2022

Abstract:Background: Most newly diagnosed oro- & hypopharngeal cancers (OPC, HPC) are treated with (chemo) RT with curative intent but at the consequence of adverse effects on quality of life. We investigated if using DO-IMRT to reduce RT dose to the dysphagia/aspiration related structures (DARS) improved swallowing function compared to S-IMRT. Method(s): Patients with T1-4, N0-3, M0 OPC/HPC were randomised 1:1 to S-IMRT (65 Gray (Gy)/30 fractions (f) to primary & nodal tumour; 54Gy/30f to remaining pharyngeal subsite & nodal areas at risk of microscopic disease) or DO-IMRT. The volume of the superior & middle pharyngeal constrictor muscle (PCM) (OPC) or inferior PCM (HPC) lying outside the high-dose target volume was set a mandatory mean dose constraint in DO-IMRT. Treatment allocation was by minimisation balanced by centre, use of induction/concomitant chemotherapy, tumour site & AJCC stage. Primary endpoint was mean MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after RT. Secondary endpoints included University of Washington (UW)-Qol, Performance Status Scale Head & Neck (PSS-HN) domain scores (range: 0-100), swallow volume, swallow capacity and local control. Result(s): 112 patients (56 S-IMRT, 56 DO-IMRT) were randomised from 22 UK & Ireland centres from 06/2016 – 04/2018. 111/112 had RT doses as prescribed (1 patient died before RT). Outcome measures at 12 and 24 months are summarised below. DO-IMRT had higher MDADI scores at 12 (p = 0.04) and 24 (p = 0.07) months. Clinically important improvements in swallowing function were seen in patients receiving DO-IMRT using PSS-HN domains and the UW-QoL tool. Conclusion(s): DO-IMRT improved patient reported swallowing function compared with S-IMRT. Improvements were seen in overall MDADI as well as functional scores in both PSS-HN and UW-QoL.

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PROMPTS RCT of screening MRI for spinal cord compression in prostate cancer (ISRCTN74112318) (2022)

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Type of publication:Conference abstract

Author(s):Dearnaley D.; Hinder V.; Hijab A.; Horan G.; *Srihari N.; Rich P.; Houston G.; Henry A.; Gibbs S.; Venkitaraman R.; Cruickshank C.; Hassan S.; Mason M.; Pedley I.; Payne H.; Brock S.; Wade R.; Robinson A.; Din O.; Lees K.; Murray J.; Parker C.; Griffin C.; Sohaib A.; Hall E.

Citation:Radiotherapy and Oncology. Conference: ESTRO 2022. Copenhagen Denmark. 170(Supplement 1) (pp S78-S80), 2022. Date of Publication: May 2022.

Abstract:Purpose or Objective Early diagnosis of malignant spinal cord compression (SCC) is crucial as pre-treatment neurologic status is the major determinant of outcome. In metastatic castrate resistant prostate cancer (mCRPC) SCC is a significant cause of diseaserelated morbidity. In the PROMPTS trial we investigated whether screening for SCC with spinal MRI, with pre-emptive treatment if radiological SCC (rSCC) was detected, reduced the incidence of clinical SCC (cSCC) in asymptomatic mCRPC patients. Materials and Methods PROMPTS is a phase III parallel-group, randomised controlled superiority trial. CRPC patients aged at least 18 years with spinal metastases without related back pain or neurological symptoms, no previous SCC, and no spinal MRI in previous 12 months were eligible. Participants were randomly allocated (1:1 ratio) to control (no MRI) or screening spinal MRI. Allocation was not masked. A validated epidural spinal cord compromise scale (ESCC) was used. Pre-emptive treatment and 6-monthly spinal MRI were offered to patients with screen-detected rSCC. The primary endpoint was incidence of cSCC at 12 months. Results Between Feb 26, 2013 and April 25, 2017, we randomly assigned 420 men from 45 UK centres to control (n=210) or screening MRI (n=210). Median age was 74 years (IQR:68-79), 53% (222/420) had normal alkaline phosphatase and median PSA was 48.0ng/ml (IQR:17-162). rSCC was detected at screening in 61/200 (30.5%) intervention group patients. Concordance of local and central assessments of rSCC was good (92.4%). At 12 months, the cumulative incidence of cSCC was 6.7% (95% CI 3.8-10.6) in the control group and 4.3% (2.1-7.7) in the intervention group (Gray's test p=0.119, HR:0.64 95%CI:0.37-1.11, Fig 1). In the intervention group cSCC developed more commonly in the rSCC +ve cases (11.5%) than the rSCC -ve cases (1.3%) and the rSCC-ve group had significantly less cSCC than the control group (Gray's test p=0.04, Fig2). Intervention for rSCC was with radiotherapy (RT) in 50/61 (82%) cases, only 4% progressed at the treated sites. RT was not given to 18 sites with early rSCC (ESCC 1a-b,17: 1c, 1) but none progressed at 6 months. At the time of cSCC 70% of patients were ambulant and 18% of non-ambulant patients regained function post-RT. More spinal RT was given in the intervention than control group (86vs49 courses) but the use of additional systemic therapy was significantly less by 12 months (54%vs70%, Gray's test p=0.003). Conclusion We found no statistically significant differences in incidence of cSCC between the intervention and control groups. MRI screen-detected early rSCC lesions do not always progress to cSCC with contemporary systemic management of CRPC and observation may be reasonable for ESCC grade 1a/b lesions. However these patients remain at substantial risk of developing new sites of cSCC. Further efforts to better identify patients at high risk for rSCC and cSCC are warranted to refine selection of groups for screening spinal MR.

Crucial, complex, caring: a new professional development framework for Lung Cancer Nurse Specialists (2022)

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Type of publication:Conference abstract

Author(s):Roberts J.; Barton P.; Clayton K.; Fenemore J.; Ivey S.; *McAdam J.; Shepherd P.

Citation:Lung Cancer. Conference: 20th Annual British Thoracic Oncology Group Conference 2022. Virtual, Online. 165(Supplement 1) (pp S40), 2022. Date of Publication: March 2022.

Abstract:Introduction: Lung cancer specialist nursing is a varied, valuable and rewarding career, and the need for lung cancer nurse specialists (LCNS) is increasing. Lung Cancer Nursing UK (LCNUK) wants to encourage nurses to aspire to becoming an LCNS, and to support those already working in lung cancer teams to flourish professionally. We want employers to recognise LCNS' capabilities and to recruit and reward them accordingly. LCNUK therefore set out to draft the first professional development framework for LCNS. The Framework is intended to guide nurses, line managers and employers on the core skills, knowledge and expertise that LCNS will gain and demonstrate as they progress in role. Method(s): LCNUK convened a working group which reviewed exemplars and supporting literature. The team produced a draft framework setting out the qualifications, skills and capabilities needed by nurses operating at different levels, aligned with the (Figure Presented) four pillars of advanced practice. Feedback on the draft was sought from expert stakeholders before the final document was approved by the LCNUK Steering Committee. The Framework was developed in a collaboration between LCNUK and MSD, who funded a policy consultancy to provide secretariat support. LCNUK retained editorial independence of the framework content. Result(s): The Framework sets out the qualifications, clinical skills, knowledge, leadership and management and research capabilities that LCNUK expects aspiring and existing LCNS to demonstrate or be working towards. It includes case studies of nurses' career journeys and an example of a successful case for job matching and re-banding. The Framework is available on the LCNUK website at www.lcnuk.org. Conclusion(s): The Framework asserts the crucial role of LCNS in managing safety-critical and complex patient care and in leading service delivery and improvement. We hope it will prove a valuable tool to nurses, employers and policymakers in understanding the complexity and importance of this essential role.

Not All That Glows Is Malignant: Actinomycosis as a Rare Mimic of Lung Cancer (2022)

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Type of publication:Conference abstract

Author(s):*Ekhelikar S.; Muthusami R.; *Orme R.; *Ahmad N.

Citation:American Journal of Respiratory and Critical Care Medicine. Conference: International Conference of the American Thoracic Society, ATS 2022. San Francisco, CA United States. 205(1) (no pagination), 2022.

Abstract:Introduction: Pulmonary actinomycosis is a rare bacterial infection that can mimic malignant and chronic suppurative lung conditions, and therefore is often misdiagnosed initially as one of the more common differential diagnoses. The challenge lies in diagnosing this condition prior to surgery as it is completely curable with antibiotics. Case description: A 48 year old man, cigarette smoker and previous intravenous drug user, presented with exertional breathlessness, persistent cough and night sweats. There was no fever or weight loss. A Chest Xray (CXR) and Computerised Tomography (CT) scan showed a left upper lobe cavitating lesion leading to differential diagnoses of bronchogenic malignancy and tuberculosis (TB). A Positron Emission Tomography (PET) scan confirmed a fluorodeoxyglucose (FDG) avid left upper lobe cavitating lesion with enlarged FDG avid thoracic lymphadenopathy. Bronchoscopy and Endobronchial Ultrasound (EBUS) were nondiagnostic. He underwent left upper lobectomy with histopathology confirming Pulmonary actinomycosis and was commenced on Amoxicillin treatment. <br/>Discussion(s): Pulmonary actinomycosis is the third most common type of actinomycosis, behind cervicofacial and abdominal, constituting 15% of total cases. It can occur at all ages, but most case series describe a peak incidence in the 4th and 5th decades. Symptoms are non-specific and often mimic those of it's more common differentials as above and so diagnosing this condition early presents a challenge. Basic laboratory tests reflect the non-specific inflammatory nature of the disease. Imaging modalities (CXR, CT, PET) are helpful, but not diagnostic. The gold standard for diagnosis remains histological examination & bacterial culture of lung biopsy specimen. Histopathologic evidence of granulomas containing neutrophils and sulfur granules with Actinomyces colonies are the hallmark of actinomycosis. Recent data suggests it is increasingly possible to avoid unwarranted surgical procedures, by performing bronchoscopic and percutaneous biopsy techniques. These represent the best chance at preventing unnecessary surgery and should be pursued as they can help exclude malignancy. Penicillin remains the drug of choice for Pulmonary actinomycosis and with correct treatment, the prognosis is excellent. However, those with complications may still require surgery. The chief challenge with Pulmonary actinomycosis is identifying it early, because it is rare, and it also mimics diseases like lung cancer and TB often. We were unable to exclude malignancy with pre-surgical diagnostics and so our patient had surgery. However, clinicians should be aware and consider Pulmonary actinomycosis as an important differential when investigating cavitating lung lesions as diagnosing it early could help prevent physical and psychological morbidity, including unwarranted surgery. (Figure Presented).

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Comparison of multiple gene expression platforms for measuring a bladder cancer hypoxia signature (2022)

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Type of publication:
Journal article

Author(s):
Smith TAD; Lane B; More E; Valentine H; Lunj S; Abdelkarem OA; Irlam-Jones J; Shabbir R; Vora S; *Denley H; Reeves KJ; Hoskin PJ; Choudhury A; West CML

Citation:
Molecular Medicine Reports, 2022 Aug; Vol. 26 (2)

Abstract:
Tumour hypoxia status provides prognostic information and predicts response to hypoxia modifying treatments. A previous study by our group derived a 24 gene signature to assess hypoxia in bladder cancer. The objectives of the present study were to compare platforms for generating signature scores, identify cut off values for prospective studies, assess intra tumour heterogeneity and confirm hypoxia relevance. Briefly, RNA was extracted from prospectively collected diagnostic biopsies of muscle invasive bladder cancer (51 patients), and gene expression was measured using customised Taqman Low Density Array (TLDA) cards, NanoString and Clariom S arrays. Cross platform transferability of the gene signature was assessed using regression and concordance analysis. The cut off values were the cohort median expression values. Intra and inter tumour variability were determined in a retrospective patient cohort (n=51) with multiple blocks (2 18) from the same tumour. To demonstrate relevance, bladder cancer cell lines were exposed to hypoxia (0.1% oxygen, 24 h), and extracted RNA was run on custom TLDA cards. Hypoxia scores (HS) values showed good agreement between platforms: Clariom S vs. TLDA (r=0.72, P<0.0001; concordance 73%); Clariom S vs. NanoString (r=0.84, P<0.0001; 78%); TLDA vs. NanoString (r=0.80, P<0.0001; 78%). Cut off values were 0.047 (TLDA), 7.328 (NanoString) and 6.667 (Clariom S). Intra tumour heterogeneity in gene expression and HS (coefficient of variation 3.9%) was less than inter tumour (7.9%) variability. HS values were higher in bladder cancer cells exposed to hypoxia compared with normoxia (P<0.02). In conclusion, the present study revealed that application of the 24 gene bladder cancer hypoxia signature was platform agnostic, cut off values determined prospectively can be used in a clinical trial, intra tumour heterogeneity was low and the signature was sensitive to changes in oxygen levels in vitro.

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Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial (2022)

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Type of publication:
Randomised controlled trial

Author(s):
Parker CC; James ND; Brawley CD; Clarke NW; Ali A; Amos CL; Attard G; Chowdhury S; Cook A; Cross W; Dearnaley DP; Douis H; Gilbert DC; Gilson C; Gillessen S; Hoyle A; Jones RJ; Langley RE; Malik ZI; Mason MD; Matheson D; Millman R; Rauchenberger M; Rush H; Russell JM; Sweeney H; Bahl A; Birtle A; Capaldi L; Din O; Ford D; Gale J; Henry A; Hoskin P; Kagzi M; Lydon A; O'Sullivan JM; Paisey SA; Parikh O; Pudney D; Ramani V; Robson P; *Srihari NN; Tanguay J; Parmar MKB; Sydes MR; STAMPEDE Trial Collaborative Group

Citation:
PLoS Medicine, 2022 Jun 07; Vol. 19 (6), pp. e1003998

Abstract:
Background: STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL).Methods and Findings: Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively.Conclusions: Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC.Trial Registration: ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544.

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Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476) (2022)

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Type of publication:Randomised controlled trial

Author(s):James N.D.; Clarke N.W.; Cook A.; Ali A.; Hoyle A.P.; Attard G.; Brawley C.D.; Chowdhury S.; Cross W.R.; Dearnaley D.P.; de Bono J.S.; Montana C.D.; Gilbert D.; Gillessen S.; Gilson C.; Jones R.J.; Langley R.E.; Malik Z.I.; Matheson D.J.; Millman R.; Parker C.C.; Pugh C.; Rush H.; Russell J.M.; Berthold D.R.; Buckner M.L.; Mason M.D.; Ritchie A.W.; Birtle A.J.; Brock S.J.; Das P.; Ford D.; Gale J.; Grant W.; Gray E.K.; Hoskin P.; Khan M.M.; Manetta C.; McPhail N.J.; O'Sullivan J.M.; Parikh O.; Perna C.; Pezaro C.J.; Protheroe A.S.; Robinson A.J.; Rudman S.M.; Sheehan D.J.; *Srihari N.N.; Syndikus I.; Tanguay J.; Thomas C.W.; Vengalil S.; Wagstaff J.; Wylie J.P.; Parmar M.K.; Sydes M.R.

Citation:
International Journal of Cancer. 151(3) (pp 422-434), 2022. Date of Publication: 01 Aug 2022.

Abstract:Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multi-arm, multi-stage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3yrs after the first results. Standard-of-care (SOC) was androgen deprivation therapy. The comparison randomized patients 1:1 to SOC-alone with or without daily abiraterone acetate 1000mg+prednisolone 5mg (SOC+AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards & flexible parametric models, adjusted for baseline stratification factors. 1003 patients were contemporaneously randomized (Nov-2011–Jan-2014): median age 67yr; 94% newly-diagnosed; metastatic disease risk group: 48% high, 44% low, 8% un-assessable; median PSA 97ng/mL. At 6.1yr median follow-up, 329 SOC-alone deaths (118 low-risk, 178 high-risk) and 244 SOC+AAP deaths (75 low-risk, 145 high-risk) were reported. Adjusted HR = 0.60 (95%CI:0.50-0.71; P =0.31×10-9 ) favoured SOC+AAP, with 5-yr survival improved from 41% SOC-alone to 60% SOC+AAP. This was similar in low-risk (HR = 0.55; 95%CI:0.41-0.76) and high-risk (HR = 0.54; 95%CI:0.43-0.69) patients. Median and current maximum time on SOC+AAP was 2.4yr and 8.1yr. Toxicity at 4yr post-randomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC+abiraterone acetate + prednisolone, irrespective of metastatic disease risk group.

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