Androgen deprivation therapy in advanced prostate cancer: insights from a real-world patient survey on health-related quality of life and information and communication sources.

PURPOSE: Androgen deprivation therapy (ADT) is a cornerstone treatment for advanced and metastatic prostate cancer. Real-world and patient-reported insights into ADT's impact on health-related quality of life (HRQoL) and communication experiences in healthcare settings remain underexplored. This patient organisation-initiated online survey aimed to assess these aspects. METHODS: Between December 2022 and August 2023, the patient organisation Think Blue Vlaanderen and the AZ Sint-Jan Hospital (Bruges, Belgium) invited ADT-treated patients to participate in a prospective, online, cross-sectional, patient-reported outcome survey. Demographic, clinical, HRQoL (FACT and EPIC-26), communication sources and information modality data were collected. Descriptive statistics and comparative analyses were applied. RESULTS: A total of 276/312 (88.5%) participating patients were on ADT at time of survey administration and completion, with the majority receiving a 3-monthly regimen. Sexual HRQoL was low and narrowly distributed (median (IQR): 16.7 (16.7-16.7)), with 84% of patients having erectile dysfunction (ED). Patients finding their ED problematic were more likely to seek pharmaceutical treatment. Hormonal HRQoL was widely distributed (median (IQR): 65 (45-85)), which improved with prolonged ADT duration. Physically active patients reported less lack of energy, but increased hot flashes. Within consistent FACT-G summary scores (median (IQR): 64.50 (54.75-77.00)), improved emotional wellbeing with prolonged ADT was noted. Multidisciplinary communication and multimodal information provision improved patient satisfaction. CONCLUSION: Patient organisation-initiated surveys offer real-world and patient-reported insights. Patient-tailored HRQoL assessments and longitudinal follow-up, physical activity, and multidisciplinary and multimodal communication approaches are warranted to improve patient-centred care in patients receiving ADT.

Comparison of prone and supine positioning for breast cancer radiotherapy using REQUITE data: dosimetry, acute and two years physician and patient-reported outcomes.

OBJECTIVE: Most patients receive whole breast radiotherapy in a supine position. However, two randomised trials showed lower acute toxicity in prone position. Furthermore, in most patients, prone positioning reduced doses to the organs at risk. To confirm these findings, we compared toxicity outcomes, photographic assessment, and dosimetry between both positions using REQUITE data. METHODS: REQUITE is an international multi-centre prospective observational study that recruited 2069 breast cancer patients receiving radiotherapy. Data on toxicity, health-related quality of life (HRQoL), and dosimetry were collected, as well as a photographic assessment. A matched case control analysis compared patients treated prone (n = 268) versus supine (n = 493). Exact matching was performed for the use of intensity-modulated radiotherapy, boost, lymph node irradiation, chemotherapy and fractionation, and the nearest neighbour for breast volume. Primary endpoints were dermatitis at the end of radiotherapy, and atrophy and cosmetic outcome by photographic assessment at two years. RESULTS: At the last treatment fraction, there was no significant difference in dermatitis (p = .28) or any HRQoL domain, but prone positioning increased the risk of breast oedema (p < .001). At 2 years, patients treated in prone position had less atrophy (p = .01), and higher body image (p < .001), and social functioning (p < .001) scores. The photographic assessment showed no difference in cosmesis at 2 years (p = .22). In prone position, mean heart dose (MHD) was significantly lower for left-sided patients (1.29 Gy vs 2.10 Gy, p < .001) and ipsilateral mean lung dose (MLD) was significantly lower for all patients (2.77 Gy vs 5.89 Gy, p < .001). CONCLUSIONS: Prone radiotherapy showed lower MLD and MHD compared to supine position, although the risk of developing breast oedema during radiotherapy was higher. At 2 years the photographic assessment showed no difference in the cosmetic outcome, but less atrophy was seen in prone-treated patients and this seems to have a positive influence on the HRQoL domain of body image.

Vaginal morbidity, sexual functioning, and health-related quality of life in cervical cancer survivors: a cross-sectional multicenter study (VAMOS).

PURPOSE: To compare sexual/vaginal functioning between early cervical cancer (ECC) and locally advanced cervical cancer (LACC) survivors. METHODS: VAMOS was a multicenter, cross-sectional, questionnaire, noninferiority study including ECC patients treated with surgery and, if clinically indicated, adjuvant (chemo)radiotherapy and LACC patients treated with neoadjuvant (chemo)radiotherapy followed by surgery. Patient-reported outcomes (PROs) were assessed using the EORTC QLQ-C30, EORTC QLQ-CX24, and Female Sexual Functioning Index (FSFI) questionnaires. Clinical reported outcomes (ClinROs) consisted of vaginal morbidity scored according to the CTCAE v4.0 scoring system. RESULTS: One hundred forty-three patients were included. Compared to ECC patients (n = 97), LACC patients (n = 46) were significantly less sexually active in the 4 weeks prior to completion of the questionnaires (65% vs. 41%; p = .005). The primary endpoint was not met: LACC patients reported a higher mean score (more problems) for sexual/vaginal functioning than ECC patients, with a non-clinically relevant mean difference of 6.38 ([95% CI: - 6.41, 19.17]; p = .570 for noninferiority). Regarding the secondary endpoints, the prevalence of sexual dysfunction between the two groups did not differ significantly (p = 0.124). Compared to ECC patients, LACC patients did not have significantly more vaginal morbidity (adjusted odds ratio [OR] 1.51 [95% CI: 0.22, 10.29]; p = .674). Moreover, there was poor agreement between any vaginal morbidity and sexual dysfunction (Cohen's kappa of 0.17). CONCLUSION: Compared to ECC survivors, LACC survivors were significantly less sexually active and reported equivalent or worse sexual/vaginal functioning, although the proportion of patients with sexual dysfunction was similar. Clinical assessment of vaginal morbidity was poorly correlated with sexual dysfunction.

A review of the content and psychometric properties of cancer-related fatigue (CRF) measures used to assess fatigue in intervention studies.

PURPOSE: Cancer-related fatigue (CRF) is a common and debilitating consequence of cancer and its treatment. Numerous supportive care interventions have been developed to alleviate CRF; however, the diversity of outcome measures used to assess CRF limits comparability of findings. We aimed to evaluate the content and psychometric properties of measures used to assess CRF in interventions targeting fatigue, to inform the selection of suitable measures in future research. METHODS: Included measures were identified from a systematic review of interventions targeting CRF. General characteristics of each measure were extracted, and item content was assessed against domains specified by the National Comprehensive Cancer Network (NCCN) definition of CRF. Psychometric properties were evaluated against COnsensus-based Standards for the selection of heath Measurement INstruments (COSMIN) criteria. RESULTS: Of 54 measures identified, 25 met inclusion criteria. Seventeen were fatigue-specific and eight a fatigue subscale or single item within a broader measure. Only 14 (56%) were specifically developed for cancer populations. Content coverage according to the NCCN CRF definition ranged from 0 to 75%. Evidence for fulfilment of COSMIN criteria in cancer populations ranged from 0 to 93%, with only five measures meeting > 70% of the COSMIN criteria. CONCLUSION: The Piper Fatigue Scale-Revised had good content coverage, but did not comprehensively address COSMIN criteria. The EORTC-FA12 and FACIT/FACT-F had excellent psychometric properties, with each capturing different aspects of fatigue. Ultimately, the choice of CRF measure should be guided by the research question and the CRF domains most relevant to the particular research context.

Exercise prescription dose for castrate-resistant prostate cancer patients: a phase I prescription dose escalation trial.

PURPOSE: To determine the start exercise prescription dose in metastatic castrate-resistant prostate cancer (mCRPC) patients receiving second-line hormone treatment and recommended phase II exercise prescription. METHODS: Patients were enrolled in a 3 + 3 dose escalation phase I trial of aerobic, resistance, and flexibility exercises to evaluate dose-limiting tolerance and safety. Tolerance was defined as Borg score ≤ 16 and safety (pain) as a visual analogue scale score (VAS) ≤ 3 and CTCAE grade < 2. Dose level 1 (escalation start dose) was set at 15 min. Aerobic training (50-80% HRmax warm-up and cooling-down; and 65-80% HRmax. core), 1 set with 8-10 repetitions (reps.) resistance training (50-60% 1-RM, 8 exercises), and 1 set (30s) with 2 reps flexibility training (5 exercises). The prescription dose escalation was designed in four levels (from dose -1 to 3), with a dose escalation in volume and intensity of the exercises. RESULTS: Nine patients were included in two dosing cohorts and were under active treatment (n = 4 abiraterone acetate and n = 5 enzalutamide). Dose limiting safety concerns were observed in 2 out of 3 patients in dose level 2 and 1 patient out of 6 in dose level 1 due to VAS > 3 during resistance training and/or flexibility training. No tolerance issues were observed in the two dosing cohorts. The optimal start exercise prescription dose was set at dose level 1 due to safety issues at dose level 2. CONCLUSION: Our findings suggest that exercise is perceived tolerable in mCRPC patients receiving second-line hormone therapy. Caution is indicated on safety during performance of the exercises.

Development of a pre- and postoperative physical activity promotion program integrated in the electronic health system of patients with bladder cancer (The POPEYE study): An intervention mapping approach.

INTRODUCTION: Uptake of sufficient physical activity before and after radical cystectomy is important to improve physical and psychosocial outcomes in bladder cancer (BC) patients. METHODS: In this paper, we describe the development of an evidence-based and theory-informed intervention, guided by the steps of the Intervention Mapping approach, to promote physical activity before and after radical cystectomy in patients with BC. RESULTS: The intervention is a home-based physical activity program. The preoperative timeframe of the intervention is 4 or 12 weeks, depending on administration of neoadjuvant chemotherapy. Postoperatively, the intervention will last for 12 weeks. The intervention consists of a digital oncological platform (DOP), several consultations with healthcare professionals, personal booklet and follow-up phone calls. DOP includes information, diaries, visual representation of progress, mailbox, videos of peers and treating physician explaining the benefits of physical activity, photo material of exercises and a walking program with an activity tracker. Individual goals will be set and will be self-monitored by the patient through DOP. Patients will receive alerts and regular feedback. CONCLUSIONS: Intervention Mapping ensures transparency of all intervention components and offers a useful approach for the development of behaviour change interventions for cancer patients and for translation of theories into practice.

Health-related quality of life overview after different curative treatment options in muscle-invasive bladder cancer: an umbrella review.

PURPOSE: This umbrella review aims to evaluate the quality, summarize and compare the conclusions of systematic reviews investigating the impact of curative treatment options on health-related quality of life (HRQoL) in muscle-invasive bladder cancer (MIBC). METHODS: The Cochrane Library, MEDLINE, Embase and Web of Science were searched independently by two authors from inception until 06 January 2020. Systematic reviews and meta-analyses assessing the impact of any curative treatment option on HRQol in MIBC patients were eligible. Risk of bias was assessed using the AMSTAR 2 tool. RESULTS: Thirty-two reviews were included. Robot-assisted RC with extracorporeal urinary diversion and open RC have similar HRQoL (n = 10). Evidence for pelvic organ-sparing RC was too limited (n = 2). Patients with a neobladder showed better overall and physical HRQoL outcomes, but worse urinary function in comparison with ileal conduit (n = 17). Bladder-preserving radiochemotherapy showed slightly better urinary and sexual but worse gastro-intestinal HRQoL outcomes in comparison with RC patients (n = 6). Quality of the reviews was low in more than 50% of the available reviews and most of the studies included in the reviews were nonrandomized studies. CONCLUSION: This umbrella review gives a comprehensive overview of the available evidence to date.

Patient- versus physician-reported outcomes in prostate cancer patients receiving hypofractionated radiotherapy within a randomized controlled trial.

PURPOSE: The risk of developing acute radiotherapy(RT)-induced side effects may increase with hypofractionated RT. To detect treatment-related side effects, patient-reported outcomes (PROs) might be more reliable than physician-reported outcomes. Therefore, we tried to evaluate the rate of agreement between urinary and gastrointestinal (GI) side effects and the prevalence of side effects reported by patients and by physicians. METHODS: Data from a randomized controlled trial (RCT) comparing two hypofractionated RT schedules were used. Urinary (nocturia, incontinence, frequency, dysuria, and urgency) and GI (obstruction, diarrhea, vomiting, nausea, bloating, hemorragia, and incontinence) symptoms measured by the EORTC QLQ-C30 and PR-25 were used for PROs. The same symptoms were scored by the physician using the Common Terminology Criteria Adverse Events v4.0. Outcomes were reported at baseline, end of treatment, month 1, and month 3. PROs and physician-reported outcomes were converted in two categories (0 = no symptoms; 1 = symptoms of any severity) and were correlated using the kappa (κ) correlation statistics. Values below 0.40 were considered low agreement. In addition, the prevalence of symptoms was calculated. RESULTS: Data from 160 patients were used. The mean value for Cohen's κ was 0.31 (ranging between 0.04 and 0.55) and 0.23 (ranging between 0.04 and 0.47) for urinary and GI symptoms, respectively. Except for three symptoms at baseline, all symptoms reported by patients were higher than those reported by physicians. CONCLUSION: There is low agreement between symptoms reported by patients and physicians, with high rates of underreporting by the physician.

Understanding physical activity behavior in patients with bladder cancer before and after radical cystectomy: a qualitative interview study.

OBJECTIVE:: To explore the determinants of physical activity in patients with bladder cancer before and after radical cystectomy. DESIGN:: A qualitative research design using semi-structured face-to-face interviews. SETTING AND SUBJECTS:: A total of 30 interviews were conducted with people diagnosed with bladder cancer and treated with radical cystectomy at Ghent University Hospital. MAIN MEASURES:: The interviews were audiotaped and transcribed verbatim. Framework analysis with constant comparison between and within interviews was applied until final topics were derived from interpreting the data. RESULTS:: Physical activity behavior in patients with bladder cancer is determined multifactorial with condition-related (e.g. urinary symptoms, comorbidities), therapy-related (e.g. fatigue, diarrhea), patient-related (e.g. outcome expectations, coping skills, definitions of physical activity), social/economic-related (e.g. social support, attractive environment) and health system-related (e.g. physicians' advice, information) factors. CONCLUSION:: The results of this study can guide the development of theory-based behavior change interventions to increase physical activity in bladder cancer patients.

Clinical pathway improves implementation of evidence-based strategies for the management of androgen deprivation therapy-induced side effects in men with prostate cancer.

OBJECTIVES: To assess the effects of a prostate cancer (PCa) clinical pathway on the implementation of evidence-based strategies for the management of androgen deprivation therapy (ADT)-induced side effects. PATIENTS AND METHODS: A clinical pathway was introduced at hospital level in 2015. The pathway consists of evidence-based strategies for the management of ADT-induced side effects. All patients with PCa receiving ADT for >6 months were eligible to enter the clinical pathway. Data on recommended evidence-based strategies were retrospectively extracted from the electronic health records of all eligible patients in the year before (2014) and the year of implementation of the pathway (2015). Descriptive statistics were used for patient characteristics. The chi-squared test (or Fisher's exact test) and Mann-Whitney U-test were used to compare results in the control group with those in the intervention group. RESULTS: In total, 126 patients were included in the control group and 132 patients in the intervention group. Baseline patient characteristics were well balanced. After implementation of the pathway, metabolic, bone and cardiac risk assessment screenings were more frequently applied in the intervention group (metabolic 46% vs 4%; bone 58% vs 10%; cardiac 61% vs 16%; P < 0.001). Advice on strategies preventing ADT-induced side effects was more frequently provided in the intervention group (exercise 62% vs 11%; nutrition 58% vs 10%; psycho-education 54% vs 13%; P < 0.001). CONCLUSION: A clinical pathway for patients with PCa improved the implementation of evidence-based strategies for the management of ADT-induced side effects. A clinical pathway could serve as a method to bridge the gap between evidence-based guidelines and daily clinical practice.

A systematic review of exercise and psychosocial rehabilitation interventions to improve health-related outcomes in patients with bladder cancer undergoing radical cystectomy.

OBJECTIVE: Summarizing the evidence on the effects of pre- and postoperative exercise and psychosocial rehabilitation interventions on patient-reported outcomes (PROs) and physical fitness in bladder cancer patients undergoing radical cystectomy. DATA SOURCES: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Web of Science and the Physiotherapy Evidence Database were searched independently by two authors from inception until 10 November 2017. Cited references of the studies and citing references retrieved via Web of Science were also checked. REVIEW METHODS: Randomized controlled trials (RCTs) and non-randomized studies assessing effects of exercise and psychosocial interventions in bladder cancer patients undergoing radical cystectomy were eligible. Primary outcome measures were PROs and physical fitness. Risk of bias was assessed using the Cochrane Collaboration tool and the Newcastle-Ottawa Scale. RESULTS: Five RCTs (three exercise and two psychosocial studies) and one non-randomized psychosocial study comprising 317 bladder cancer patients were included. Timing of the intervention was preoperative ( n = 2), postoperative ( n = 2) or both pre- and postoperative ( n = 2). Positive effects of exercise were found for physical fitness ( n = 3), some health-related quality-of-life (HRQoL) domains ( n = 2), personal activities in daily living ( n = 1) and muscle strength ( n = 1). Psychosocial interventions showed positive effects on anxiety ( n = 1), fatigue ( n = 1), depression ( n = 1), HRQoL ( n = 1) and posttraumatic growth ( n = 1). Quality assessment showed most shortcomings with sample sizes and strong heterogeneity was observed between studies. CONCLUSION: The evidence relating to the effects of exercise in bladder cancer is very limited and is even less for psychosocial interventions.

Health-related quality of life in men with oligometastatic prostate cancer following metastases-directed stereotactic body radiotherapy: Real-world data from the E2-RADIatE OligoCare cohort.

Objective: To evaluate the impact of metastases-directed stereotactic body radiotherapy (SBRT) on health-related quality of life (HRQoL) in men with oligometastatic prostate cancer (PCa) using real-world data from the OligoCare cohort. Materials and methods: OligoCare is a pragmatic, observational cohort designed to assess the impact of metastases-directed SBRT on patients with oligometastatic disease (OMD). We report an interim analyses of the secondary endpoint HRQoL, assessed using the EORTC QLQ-C30, within six months of metastases-directed SBRT for oligometastatic disease in men with PCa among the first 1600 registered patients. HRQoL data collection was optional within the OligoCare cohort. To compare HRQoL between baseline and first follow-up assessment, a Wilcoxon signed-rank test was used. A multiple linear regression model was used to explore the HRQoL associations with predefined factors. Results: Out of the 1600 registered patients, 658 were treated for oligometastatic PCa, of which 233 had baseline QoL data and 132 patients had both baseline and follow-up HRQoL data. At baseline, most patients had a WHO performance status of 0 or 1 (87 %), were de-novo oligometastatic (79 %), had one metastasis (90 %), and had a good overall global health status (mean 80.81, SD16.11, IQR 75-92). 51 % received hormonal therapy as concomitant systemic treatment. Patients with comorbidities as assessed by the Charlson Comorbidity index had a worse global health status at baseline (-4.88, 95 % CI:-9.35, -0.42). No clinically meaningful significant difference in global health status was observed at first assessment following SBRT (median 3.0 months) compared with baseline (mean difference 2.27, 95 % CI:-1.54, 6.08). Upon evaluating the proportions, meaningful clinically important differences (a 10-point or more difference) was observed in, 17 % and 11 % of the patients reporting deterioration and improvement of global health status, respectively. Conclusion: Metastases-directed stereotactic body radiotherapy had no negative impact on global HRQoL within the first six months after treatment.

Patient-reported outcomes and functional exercise capacity in a real-life setting in non-small cell lung cancer patients undergoing stereotactic body radiotherapy: the Lung PLUS study.

Introduction: To better understand the impact of stereotactic body radiotherapy (SBRT) and its treatment-related toxicity on early-stage non-small cell lung cancer (ES-NSCLC) patients, we conducted the Lung PLUS study in a real-world setting. Methods: This is a monocentric prospective longitudinal study up to 12 months post-treatment, evaluating clinician- and patient-reported toxicity (resp. CTCAE and PRO-CTCAE), health-related quality of life (HRQoL) (EORTC QLQ-C30 and LC-13), activities of daily living (HAQ-DI) and functional exercise capacity (6 Minute Walking Test (6MWT)). A mixed model approach was applied to analyze the data. Results: At baseline, clinicians and patients (n=51) reported mostly fatigue (63% vs 79%), cough (49% vs 75%) and dyspnea (65% vs 73%) of any grade. Dyspnea (p=.041) increased over time. Meaningful clinical improvements were particularly seen in pain, fatigue, and cough. Clinician reported clinically meaningful improvements and deteriorations over time in fatigue, cough, and dyspnea. Almost at every timepoint, more people reported deterioration to the clinician than improvement in aforementioned toxicities. Overall HRQoL (p=.014), physical (p=.011) and emotional (p<.001) functioning improved over time. At baseline, patients had a moderate daily functioning score and walked an average distance of 360 meters. No statistically significant differences were found in daily functioning and exercise capacity over time. Conclusion: Our study showed an increase in patient-reported toxicity and dyspnea, without impacting functional status, following SBRT. Overall HRQoL, physical and emotional functioning improved over time. Understanding the impact of treatment on patient-reported outcomes is crucial to identify the needs/problems of patients to enhance their HRQoL.

Experiences of Men With Prostate Cancer Participating in a Clinical Pathway With a Supervised Group-based Exercise Program to Combat Androgen Deprivation-Induced Side Effects: A Qualitative Focus Group Study.

OBJECTIVES: A clinical pathway in daily practice improved implementation of evidence-based strategies for the management of androgen deprivation-induced side effects in men with prostate cancer. This study aimed to explore patients' expectations and reasons to start with the clinical pathway; explore patients' experiences and attitudes toward the pathway; and identify key pathway ingredients and examine patients' attitudes about a possible transition toward the home environment after a hospital-based pathway participation. DATA SOURCES: Focus group interviews were conducted through purposeful sampling, consisting of former and current participants of the clinical pathway at Ghent University Hospital. Data was audiotaped and transcribed verbatim, coded in NVivo12, and thematically and inductively analyzed through constant comparisons. CONCLUSION: Men with prostate cancer have positive experiences toward the use of a holistic multidisciplinary approach (ie, clinical pathway) to combat androgen deprivation therapy-induced side effects in practice. Patients identified several key ingredients of the pathway, such as peer support, physiotherapist involvement, and availability of a multidisciplinary team. Patients were, however, reluctant to continue the exercise component at home because of negative attitudes toward a public gym, practical issues, absence of known facilitators, and other priorities. IMPLICATIONS FOR NURSING PRACTICE: Referral by a health care provider remains an important motivator for pathway participation. Peer support, physiotherapist involvement, and availability of a multidisciplinary team are crucial components of the clinical pathway and should be taken into account when developing and implementing similar pathways to increase program uptake in daily practice.

Comparing symptom reporting by prostate cancer patients and healthcare professionals in the international multicentre REQUITE study.

INTRODUCTION: Previous studies showed that healthcare professionals and patients had only moderate to low agreement on their assessment of treatment-related symptoms. We aimed to determine the levels of agreement in a large cohort of prostate cancer patients. METHODS: Analyses were made of data from 1,756 prostate cancer patients treated with external beam radiotherapy (RT) and/or brachytherapy in Europe and the USA and recruited into the prospective multicentre observational REQUITE study. Eleven pelvic symptoms at the end of RT were compared after translating patient-reported outcomes (PROs) into CTCAE-based healthcare professional ratings. Gwet's AC2 agreement coefficient and 95% confidence intervals were calculated for each symptom. To compare severity of grading between patients and healthcare professionals, percent agreement and deviations for each symptom were graphically depicted. Stratified and sensitivity analyses were conducted to identify potential influencing factors and to assess heterogeneity and robustness of results. RESULTS: The agreement for the 11 pelvic symptoms varied from very good (AC2 > 0.8: haematuria, rectal bleeding, management of sphincter control) to poor agreement (AC2 ≤ 0.2: proctitis and urinary urgency). Fatigue had a negative impact on the agreement. Patients tended to grade symptoms more severely than healthcare professionals. Information on sexual dysfunction was missing more frequently in healthcare professional assessment than PROs. CONCLUSION: Agreement was better for observable than subjective symptoms, with patients usually grading symptoms more severely than healthcare professionals. Our findings emphasize that PROs should complement symptom assessment by healthcare professionals and be taken into consideration for clinical decision-making to incorporate the patient perspective.

PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): Acute Toxicity of a Randomized Phase 2 Trial.

BACKGROUND: Treatment recommendations for patients with limited nodal recurrences are lacking, and different locoregional treatment approaches are currently being used. OBJECTIVE: The aim of this trial is to compare metastasis-directed therapy (MDT) with or without elective nodal pelvic radiotherapy (ENRT). DESIGN, SETTING, AND PARTICIPANTS: PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM) is an international, phase 2, open-label, randomized, superiority trial (ClinicalTrials.gov identifier: NCT03569241). Patients diagnosed with positron emission tomography-detected pelvic nodal oligorecurrence (five or fewer nodes) following radical local treatment for prostate cancer were randomized in a 1:1 ratio between arm A (MDT and 6 mo of androgen deprivation therapy [ADT]) and arm B (ENRT [25 × 1.8 Gy] with MDT and 6 mo of ADT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We report the secondary endpoint acute toxicity, defined as worst grade ≥2 Common Terminology Criteria for Adverse Events v4.0 gastrointestinal (GI) or genitourinary (GU) toxicity within 3 mo of treatment. The chi-square test was used to compare toxicity between treatment arms. We also compare the quality of life (QoL) using the European Organisation for Research and Treatment of Cancer QLQ C30 and PR25 questionnaires. RESULTS AND LIMITATIONS: Between June 2018 and April 2021, 196 patients were assigned randomly to MDT or ENRT. Ninety-seven of 99 patients allocated to MDT and 93 of 97 allocated to ENRT received per-protocol treatment. Worst acute GI toxicity proportions were as follows: grade ≥2 events in three (3%) in the MDT group versus four (4%) in the ENRT group (p = 0.11). Worst acute GU toxicity proportions were as follows: grade ≥2 events in eight (8%) in the MDT group versus 12 (13%) in the ENRT group (p = 0.95). We observed no significant difference between the study groups in the proportion of patients with a clinically significant QoL reduction from baseline for any subdomain score area. CONCLUSIONS: No clinically meaningful differences were observed in worst grade ≥2 acute GI or GU toxicity or in QoL subdomains between MDT and ENRT. PATIENT SUMMARY: We found no evidence of differential acute bowel or urinary side effects using metastasis-directed therapy and elective nodal radiotherapy for the treatment of patients with a pelvic lymph node recurrence.

Genome-wide association study of treatment-related toxicity two years following radiotherapy for breast cancer.

BACKGROUND AND PURPOSE: Up to a quarter of breast cancer patients treated by surgery and radiotherapy experience clinically significant toxicity. If patients at high risk of adverse effects could be identified at diagnosis, their treatment could be tailored accordingly. This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity two years following whole breast radiotherapy. MATERIALS AND METHODS: A genome-wide association study (GWAS) was performed in 1,640 breast cancer patients with complete SNP, clinical, treatment and toxicity data, recruited across 18 European and US centres into the prospective REQUITE cohort study. Toxicity data (CTCAE v4.0) were collected at baseline, end of radiotherapy, and annual follow-up. A total of 7,097,340 SNPs were tested for association with the residuals of toxicity endpoints, adjusted for clinical, treatment co-variates and population substructure. RESULTS: Quantile-quantile plots showed more associations with toxicity above the p < 5 × 10-5 level than expected by chance. Eight SNPs reached genome-wide significance. Nipple retraction grade ≥ 2 was associated with the rs188287402 variant (p = 2.80 × 10-8), breast oedema grade ≥ 2 with rs12657177 (p = 1.12 × 10-10), rs75912034 (p = 1.12 × 10-10), rs145328458 (p = 1.06 × 10-9) and rs61966612 (p = 1.23 × 10-9), induration grade ≥ 2 with rs77311050 (p = 2.54 × 10-8) and rs34063419 (p = 1.21 × 10-8), and arm lymphoedema grade ≥ 1 with rs643644 (p = 3.54 × 10-8). Heritability estimates across significant endpoints ranged from 25% to 39%. Our study did not replicate previously reported SNPs associated with breast radiation toxicity at the pre-specified significance level. CONCLUSIONS: This GWAS for long-term breast radiation toxicity provides further evidence for significant association of common SNPs with distinct toxicity endpoints.

Large-scale meta-genome-wide association study reveals common genetic factors linked to radiation-induced acute toxicities across cancer types.

BACKGROUND: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity across 4 cancer types (prostate, head and neck, breast, and lung). METHODS: A genome-wide association study meta-analysis was performed using 19 cohorts totaling 12 042 patients. Acute standardized total average toxicity (STATacute) was modelled using a generalized linear regression model for additive effect of genetic variants, adjusted for demographic and clinical covariates (rSTATacute). Linkage disequilibrium score regression estimated shared single-nucleotide variation (SNV-formerly SNP)-based heritability of rSTATacute in all patients and for each cancer type. RESULTS: Shared SNV-based heritability of STATacute among all cancer types was estimated at 10% (SE = 0.02) and was higher for prostate (17%, SE = 0.07), head and neck (27%, SE = 0.09), and breast (16%, SE = 0.09) cancers. We identified 130 suggestive associated SNVs with rSTATacute (5.0 × 10‒8 < P < 1.0 × 10‒5) across 25 genomic regions. rs142667902 showed the strongest association (effect allele A; effect size ‒0.17; P = 1.7 × 10‒7), which is located near DPPA4, encoding a protein involved in pluripotency in stem cells, which are essential for repair of radiation-induced tissue injury. Gene-set enrichment analysis identified 'RNA splicing via endonucleolytic cleavage and ligation' (P = 5.1 × 10‒6, P = .079 corrected) as the top gene set associated with rSTATacute among all patients. In silico gene expression analysis showed that the genes associated with rSTATacute were statistically significantly up-regulated in skin (not sun exposed P = .004 corrected; sun exposed P = .026 corrected). CONCLUSIONS: There is shared SNV-based heritability for acute radiation-induced toxicity across and within individual cancer sites. Future meta-genome-wide association studies among large radiation therapy patient cohorts are worthwhile to identify the common causal variants for acute radiotoxicity across cancer types.

Bone health and therapeutic agents in advanced prostate cancer.

Prostate cancer is the most frequent genitourinary tumor worldwide. Maintaining an optimum bone health throughout the natural course of prostate cancer is an important aspect in the management of this disease, particularly in this at risk population of older and frail patients who experience bone loss related to androgen-deprivation therapy (ADT) and/or patients who develop bone metastases. The number of treatment options for advanced prostate cancer that combine ADT with docetaxel, new hormonal agents and/or radiotherapy has increased substantially in recent years. Bisphosphonates and other bone targeted agents such as denosumab have shown an improvement in bone mineral density and are suited for patients with treatment-related osteoporosis and/or bone metastases with an increased risk of skeletal-related events (SREs). In this context, the aim of this review is to analyse key aspects of bone health and therapies that can prevent the occurrence of SREs throughout the clinical course of prostate cancer, and how to combine them with new available treatments in this setting.

High weekly integral dose and larger fraction size increase risk of fatigue and worsening of functional outcomes following radiotherapy for localized prostate cancer.

Introduction: We hypothesized that increasing the pelvic integral dose (ID) and a higher dose per fraction correlate with worsening fatigue and functional outcomes in localized prostate cancer (PCa) patients treated with external beam radiotherapy (EBRT). Methods: The study design was a retrospective analysis of two prospective observational cohorts, REQUITE (development, n=543) and DUE-01 (validation, n=228). Data were available for comorbidities, medication, androgen deprivation therapy, previous surgeries, smoking, age, and body mass index. The ID was calculated as the product of the mean body dose and body volume. The weekly ID accounted for differences in fractionation. The worsening (end of radiotherapy versus baseline) of European Organisation for Research and Treatment of Cancer EORTC) Quality of Life Questionnaire (QLQ)-C30 scores in physical/role/social functioning and fatigue symptom scales were evaluated, and two outcome measures were defined as worsening in ≥2 (WS2) or ≥3 (WS3) scales, respectively. The weekly ID and clinical risk factors were tested in multivariable logistic regression analysis. Results: In REQUITE, WS2 was seen in 28% and WS3 in 16% of patients. The median weekly ID was 13.1 L·Gy/week [interquartile (IQ) range 10.2-19.3]. The weekly ID, diabetes, the use of intensity-modulated radiotherapy, and the dose per fraction were significantly associated with WS2 [AUC (area under the receiver operating characteristics curve) =0.59; 95% CI 0.55-0.63] and WS3 (AUC=0.60; 95% CI 0.55-0.64). The prevalence of WS2 (15.3%) and WS3 (6.1%) was lower in DUE-01, but the median weekly ID was higher (15.8 L·Gy/week; IQ range 13.2-19.3). The model for WS2 was validated with reduced discrimination (AUC=0.52 95% CI 0.47-0.61), The AUC for WS3 was 0.58. Conclusion: Increasing the weekly ID and the dose per fraction lead to the worsening of fatigue and functional outcomes in patients with localized PCa treated with EBRT.