Patient Perceptions in a Nonblinded Randomized Trial of Radiation Therapy Technologies: A Novel Survey Study Exploring Therapeutic Misconception.

PURPOSE: Therapeutic misconception is the tendency for a clinical trial participant to overlook the scientific objective of a clinical trial and instead believe that an experimental intervention is intended for personal therapeutic benefit. We sought to evaluate this tendency in the setting of a clinical trial of a new radiation therapy technology. METHODS: Patients with left-sided, node positive breast cancer enrolled in a randomized clinical trial evaluating intensity modulated radiation therapy with deep inspiration breath hold (IMRT-DIBH) versus 3-dimensional conformal radiation therapy (3DCRT). Patients who enrolled completed surveys at baseline, after randomization, and upon completion of radiation therapy to evaluate expectations, satisfaction, and experiences. RESULTS: Forty women participated in the survey study, with 20 in each arm. Most participants endorsed the perception that participation in the trial might result in better treatment than the current standard treatment (77%) and more medical attention than being off trial (54%). At baseline, most women (74%) believed that a new treatment technology is superior than an established one. Before randomization, 43% of participants believed IMRT-DIBH would be more effective than standard treatment with 3DCRT, none believed that 3DCRT would be more effective, 23% believed that they would be the same, and 34% did not know. None believed that IMRT-DIBH would cause worse long-term side effects, whereas 37% thought that 3DCRT would. Most (71%) reported that they would choose to be treated with IMRT-DIBH; none would have elected 3DCRT if given a choice. Nearly half (44%) in the 3DCRT arm wished that they had been assigned to the IMRT-DIBH arm; none in the IMRT-DIBH arm expressed a wish for crossover. CONCLUSIONS: Most participants reported the perception that trial participation would result in better treatment and more medical attention than off trial, hallmarks of therapeutic misconception. Our observations provide empirical evidence of a fixed belief in the superiority of new technology and highlight the importance of adjusting expectations through informed consent to mitigate therapeutic misconception.

A cross sectional study in cognitive and neurobehavioral impairment in long-term nasopharyngeal cancer survivors treated with intensity-modulated radiotherapy.

PURPOSE/OBJECTIVES: To determine neurocognitive and neurobehavioral impairment in long-term nasopharyngeal cancer survivors (NPC) treated with intensity-modulated radiotherapy (IMRT). MATERIALS/METHODS: A cross-sectional cohort of NPC ≥4 years (y) following IMRT was assessed. Objective cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and patient-reported memory was assessed with the MDASI-HN problems remembering item. Patient and family ratings of patients' neurobehavioral symptoms of apathy, disinhibition and executive dysfunction were assessed with the Frontal Systems Behavior Scale (FrSBe). Other patient-reported symptoms (MDASI-HN), mood (HADS), and quality of life (FACT-H&N) were also collected. RESULTS: Among 102 participants: M:F = 66:36; median age 56y (32-77); median time since IMRT 7.5y (4.2-11.1). Impaired MoCA scores (<23) were observed in 33 (32%). Patient and family ratings of pre-illness neurobehavioral symptoms were in the normal range (total FrSBe T-scores 53.3 and 59.0 respectively). In contrast, post-treatment patient and family T-scores were clinically impaired (64.7, 71.3 respectively), with apathy, disinhibition and executive dysfunction post-treatment ratings all significantly worse than pre-treatment (p < 0.001). Prevalence of clinically significant post-treatment disturbance was high by patient and family ratings (48%/66% apathy, 35%/53% disinhibition, 39%/56% executive dysfunction). Post-treatment neurobehavioral symptoms strongly correlated with lower quality of life (r = -0.62) and higher anxiety (r = 0.62) and depression scores (r = 0.67, all p < 0.001). Total MoCA scores did not correlate with RT dose. However, greater declines in apathy, disinhibition and executive dysfunction were associated with receiving >75 Gy to temporal lobes. CONCLUSION: NPC treated with IMRT had moderate to high rates of neurocognitive impairment and clinically significant apathy, disinhibition, and executive dysfunction.

Sexual quality of life following prostate intensity modulated radiation therapy (IMRT) with a rectal/prostate spacer: Secondary analysis of a phase 3 trial.

BACKGROUND: We previously reported the results of a phase 3 trial evaluating a prostate/rectal hydrogel spacer during prostate intensity modulated radiation therapy, which resulted in decreased rectal dose and toxicity and less decline in bowel quality of life (QOL). A secondary analysis was performed to correlate penile bulb dose and sexual QOL. METHODS AND MATERIALS: Sexual QOL was measured with the Expanded Prostate Cancer Index Composite (EPIC) by mean scores, the proportion of patients with a minimal clinically important difference (MID), and analyses of the different items composing the sexual domain. RESULTS: A total of 222 men enrolled with median follow-up of 37 months. Hydrogel reduced penile bulb mean dose, maximum dose, and percentage of penile bulb receiving 10 to 30 Gy (all P < .05) with mean dose indirectly correlated with erections sufficient for intercourse at 15 months (P = .03). Baseline EPIC was low (53 [standard deviation ± 24]) with no difference between arms (P > .1). A total of 41% (88/222) of men had adequate baseline sexual QOL (EPIC >60 (mean, 77 [± 8.3]). This subgroup at 3 years had better sexual function (P = .03) with a spacer with a smaller difference in sexual bother (P = .1), which resulted in a higher EPIC summary on the spacer arm (58 [±24.1] vs control 45 [± 24.4]) meeting threshold for MID without statistical significance (P = .07). There were statistically nonsignificant differences favoring spacer for the proportion of men with MID and 2× MID declines in sexual QOL with 53% vs 75% having an 11-point decline (P = .064) and 41% vs 60% with a 22-point decline (P = .11). At 3 years, more men potent at baseline and treated with spacer had "erections sufficient for intercourse" (control 37.5% vs spacer 66.7%, P = .046) as well as statistically higher scores on 7 of 13 items in the sexual domain (all P < .05). CONCLUSIONS: The use of a hydrogel spacer decreased dose to the penile bulb, which was associated with improved erectile function compared with the control group based on patient-reported sexual QOL.

Impact of the Primary Information Source Used for Decision Making on Treatment Perceptions and Regret in Prostate Cancer.

OBJECTIVE: To assess the impact of the primary source of information used by prostate cancer patients to select a radiation treatment on their overall treatment experience and on treatment regret. METHODS: Patients with low to favorable intermediate-risk prostate cancer treated with stereotactic body radiation therapy, intensity-modulated radiation therapy, or high-dose rate brachytherapy were surveyed. The questionnaire explored the decision-making experience, treatment experience, and treatment regret. RESULTS: In total, 322 consecutive patients were surveyed with an 86% (n=276) response rate. In total, 48% (n=132) selected their radiation oncologist as the primary information source, 23% (n=62) selected their urologist, 16% (n=44) selected the Internet, 6% (n=17) selected other patients, and 8% (n=21) selected other. In total, 39% of patients who selected the Internet as their primary information source reported their actual treatment experience to be worse than expected versus 13% of respondents who selected their urologist, 12% who selected other patients, and 2% who selected their radiation oncologist (P<0.01). Similarly, 43% who selected the Internet as their primary information source endorsed treatment regret versus 10% who selected their urologist, and 7% who selected their radiation oncologist (P<0.01). On multivariate regression, only patients who selected the Internet as their primary information source were more likely to endorse treatment regret (odds ratio, 46.47; P<0.001) and a worse treatment perception (odds ratio, 83.33; P<0.001). CONCLUSIONS: Patients who used the Internet as their primary information source were significantly more likely to endorse treatment regret and a worse than expected overall treatment experience. These data highlight the potential dangers of Internet-based resources and the importance for physicians to proactively counsel patients.

Travelling for treatment; does distance and deprivation affect travel for intensity-modulated radiotherapy in the rural setting for head and neck cancer?

OBJECTIVE: NHS England has commissioned intensity-modulated radiotherapy for head and neck cancers from Newcastle hospitals for patients in North Cumbria. This study assessed whether travel distances affected the decision to travel to Newcastle (to receive intensity-modulated radiotherapy) or Carlisle (to receive conformal radiotherapy). METHODS: All patients for whom the multidisciplinary team recommended intensity-modulated radiotherapy between December 2013 and January 2016 were included. Index of multiple deprivation scores and travel distances were calculated. Patients were also asked why they chose their treating centre. RESULTS: Sixty-nine patients were included in this study. There were no significant differences in travel distance (p = 0.53) or index of multiple deprivation scores (p = 0.47) between patients opting for treatment in Carlisle or Newcastle. However, 29 of the 33 patients gave travel distance as their main reason for not travelling for treatment. CONCLUSION: Quantitatively, travel distance and deprivation does not impact on whether patients accept intensity-modulated radiotherapy. However, patients say distance is a major barrier for access. Future research should explore how to reduce this.

Exploring Value From the Patient's Perspective Between Modern Radiation Therapy Modalities for Localized Prostate Cancer.

PURPOSE: Patients' perspectives on their treatment experiences have not been compared between modern radiation modalities for localized prostate cancer. We evaluated treatment regret and patients' perceptions of their treatment experiences to better inform our understanding of a treatment's value. METHODS AND MATERIALS: Patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT), intensity modulated radiation therapy (IMRT), or high-dose-rate (HDR) brachytherapy between 2008 and 2014 with at least 1 year of follow-up were surveyed. The questionnaire explored the decision-making experience, expectations of toxicities versus the reality, and treatment regret by means of a validated tool. RESULTS: Three hundred twenty-nine consecutive patients were surveyed, with an 86% response rate (IMRT, n=74; SBRT, n=108; HDR, n=94). The median patient age and posttreatment follow-up time were 68 years and 47 months, respectively. Eighty-two percent of patients had T1c disease with either Gleason 6 (42%) or Gleason 7 (58%) pathologic features and a median initial prostate-specific antigen of 5.8 ng/mL. Thirteen percent expressed regret with their treatment. Among patients with regret, 71% now wish they had elected for active surveillance. The incidence of regret was significantly different between treatment modalities: 5% of patients treated with SBRT expressed regret versus 18% with HDR and 19% with IMRT (P<.01). On multivariable logistic regression, patients treated with HDR versus SBRT were 7.42 times more likely to have regret, and patients treated with IMRT versus SBRT were 11.11 times more likely to have regret (P<.01 and P<.01, respectively). Significantly more patients treated with SBRT selected that their actual long-term toxicities were significantly less than originally expected, compared with IMRT and HDR patients (SBRT 43% vs IMRT 20% vs HDR 10%, P<.01). CONCLUSIONS: We found significant differences in patients' experiences between SBRT, IMRT, and HDR, with significantly less treatment regret and less toxicity than expected among SBRT patients. The majority of patients with regret would now opt for active surveillance; therefore, pretreatment counseling is essential.

Long-term decision regret after post-prostatectomy image-guided intensity-modulated radiotherapy.

INTRODUCTION: Decision regret (DR) may occur when a patient believes their outcome would have been better if they had decided differently about their management. Although some studies investigate DR after treatment for localised prostate cancer, none report DR in patients undergoing surgery and post-prostatectomy radiotherapy. We evaluated DR in this group of patients overall, and for specific components of therapy. METHODS: We surveyed 83 patients, with minimum 5 years follow-up, treated with radical prostatectomy (RP) and post-prostatectomy image-guided intensity-modulated radiotherapy (IG-IMRT) to 64-66 Gy following www.EviQ.org.au protocols. A validated questionnaire identified DR if men either indicated that they would have been better off had they chosen another treatment, or they wished they could change their mind about treatment. RESULTS: There was an 85.5% response rate, with median follow-up post-IMRT 78 months. Adjuvant IG-IMRT was used in 28% of patients, salvage in 72% and ADT in 48%. A total of 70% of patients remained disease-free. Overall, 16.9% of patients expressed DR for treatment, with fourfold more regret for the RP component of treatment compared to radiotherapy (16.9% vs 4.2%, P = 0.01). DR for androgen deprivation was 14.3%. Patients were regretful of surgery due to toxicity, not being adequately informed about radiotherapy as an alternative, positive margins and surgery costs (83%, 33%, 25% and 8% of regretful patients respectively). Toxicity caused DR in the three radiotherapy-regretful and four ADT-regretful patients. Patients were twice as regretful overall, and of surgery, for salvage vs adjuvant approaches (both 19.6% vs 10.0%). CONCLUSION: Decision regret after RP and post-prostatectomy IG-IMRT is uncommon, although patients regret RP more than post-operative IG-IMRT. This should reassure urologists referring patients for post-prostatectomy IG-IMRT, particularly in the immediate adjuvant setting. Other implications include appropriate patient selection for RP (and obtaining clear margins), and ensuring adequately discussing definitive radiotherapy as an alternative to surgery.

Patient preferences in early glottic cancer treatment.

Patients with early-stage glottic cancer are primarily treated with one of three options: endoscopic laser excision, external-beam radiation, or open conservation surgery. We sought to determine patient preferences for treatment when presented with a choice between CO2 laser resection and radiation (open conservation surgery was not offered because the endoscopic approach is preferred at our institution). This prospective cohort study was conducted at the Dalhousie University Faculty of Medicine in Halifax, Canada. Our patient population was made up of 54 men and 10 women, aged 30 to 84 years (mean: 65.0 ± 11.2). Their disease were staged as follows: carcinoma in situ, n = 11; T1a = 21; T1b = 6; and T2 = 26. Patients were quoted identical cure rates for the two treatment modalities. The controversial issue of voice outcomes was discussed, but no leading information was given to the study cohort. All 64 patients chose CO2 laser resection as opposed to radiation therapy for definitive treatment.

Hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate-risk localised prostate cancer: 2-year patient-reported outcomes of the randomised, non-inferiority, phase 3 CHHiP trial.

BACKGROUND: Patient-reported outcomes (PROs) might detect more toxic effects of radiotherapy than do clinician-reported outcomes. We did a quality of life (QoL) substudy to assess PROs up to 24 months after conventionally fractionated or hypofractionated radiotherapy in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP) trial. METHODS: The CHHiP trial is a randomised, non-inferiority phase 3 trial done in 71 centres, of which 57 UK hospitals took part in the QoL substudy. Men with localised prostate cancer who were undergoing radiotherapy were eligible for trial entry if they had histologically confirmed T1b-T3aN0M0 prostate cancer, an estimated risk of seminal vesicle involvement less than 30%, prostate-specific antigen concentration less than 30 ng/mL, and a WHO performance status of 0 or 1. Participants were randomly assigned (1:1:1) to receive a standard fractionation schedule of 74 Gy in 37 fractions or one of two hypofractionated schedules: 60 Gy in 20 fractions or 57 Gy in 19 fractions. Randomisation was done with computer-generated permuted block sizes of six and nine, stratified by centre and National Comprehensive Cancer Network (NCCN) risk group. Treatment allocation was not masked. UCLA Prostate Cancer Index (UCLA-PCI), including Short Form (SF)-36 and Functional Assessment of Cancer Therapy-Prostate (FACT-P), or Expanded Prostate Cancer Index Composite (EPIC) and SF-12 quality-of-life questionnaires were completed at baseline, pre-radiotherapy, 10 weeks post-radiotherapy, and 6, 12, 18, and 24 months post-radiotherapy. The CHHiP trial completed accrual on June 16, 2011, and the QoL substudy was closed to further recruitment on Nov 1, 2009. Analysis was on an intention-to-treat basis. The primary endpoint of the QoL substudy was overall bowel bother and comparisons between fractionation groups were done at 24 months post-radiotherapy. The CHHiP trial is registered with ISRCTN registry, number ISRCTN97182923. FINDINGS: 2100 participants in the CHHiP trial consented to be included in the QoL substudy: 696 assigned to the 74 Gy schedule, 698 assigned to the 60 Gy schedule, and 706 assigned to the 57 Gy schedule. Of these individuals, 1659 (79%) provided data pre-radiotherapy and 1444 (69%) provided data at 24 months after radiotherapy. Median follow-up was 50·0 months (IQR 38·4-64·2) on April 9, 2014, which was the most recent follow-up measurement of all data collected before the QoL data were analysed in September, 2014. Comparison of 74 Gy in 37 fractions, 60 Gy in 20 fractions, and 57 Gy in 19 fractions groups at 2 years showed no overall bowel bother in 269 (66%), 266 (65%), and 282 (65%) men; very small bother in 92 (22%), 91 (22%), and 93 (21%) men; small bother in 26 (6%), 28 (7%), and 38 (9%) men; moderate bother in 19 (5%), 23 (6%), and 21 (5%) men, and severe bother in four (<1%), three (<1%) and three (<1%) men respectively (74 Gy vs 60 Gy, ptrend=0.64, 74 Gy vs 57 Gy, ptrend=0·59). We saw no differences between treatment groups in change of bowel bother score from baseline or pre-radiotherapy to 24 months. INTERPRETATION: The incidence of patient-reported bowel symptoms was low and similar between patients in the 74 Gy control group and the hypofractionated groups up to 24 months after radiotherapy. If efficacy outcomes from CHHiP show non-inferiority for hypofractionated treatments, these findings will add to the growing evidence for moderately hypofractionated radiotherapy schedules becoming the standard treatment for localised prostate cancer. FUNDING: Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

Patient-reported quality of life after stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and brachytherapy.

BACKGROUND AND PURPOSE: Stereotactic body radiotherapy (SBRT) is being used for prostate cancer, but concerns persist about toxicity compared to other radiotherapy options. MATERIALS AND METHODS: We conducted a multi-institutional pooled cohort analysis of patient-reported quality of life (QOL) [EPIC-26] before and after intensity-modulated radiotherapy (IMRT), brachytherapy, or SBRT for localized prostate cancer. Data were analyzed by mean domain score, minimal clinically detectable difference (MCD) in domain score, and multivariate analyses to determine factors associated with domain scores at 2-years. RESULTS: Data were analyzed from 803 patients at baseline and 645 at 2-years. Mean declines at 2-years across all patients were -1.9, -4.8, -4.9, and -13.3 points for urinary obstructive, urinary incontinence, bowel, and sexual symptom domains, respectively, corresponding to MCD in 29%, 20%, and 28% of patients. On multivariate analysis (vs. IMRT), brachytherapy had worse urinary irritation at 2-years (-6.8 points, p<0.0001) but no differences in other domains (p>0.15). QOL after SBRT was similar for urinary (p>0.5) and sexual domains (p=0.57), but was associated with better bowel score (+6.7 points, p<0.0002). CONCLUSIONS: QOL 2-years after brachytherapy, IMRT, or SBRT is very good and largely similar, with small differences in urinary and bowel QOL that are likely minimized by modern techniques.

Decision regret in men undergoing dose-escalated radiation therapy for prostate cancer.

PURPOSE: Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. METHODS AND MATERIALS: We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. RESULTS: There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). CONCLUSION: Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery.

Prospective preference assessment of patients' willingness to participate in a randomized controlled trial of intensity-modulated radiotherapy versus proton therapy for localized prostate cancer.

PURPOSE: To investigate patients' willingness to participate (WTP) in a randomized controlled trial (RCT) comparing intensity-modulated radiotherapy (IMRT) with proton beam therapy (PBT) for prostate cancer (PCa). METHODS AND MATERIALS: We undertook a qualitative research study in which we prospectively enrolled patients with clinically localized PCa. We used purposive sampling to ensure a diverse sample based on age, race, travel distance, and physician. Patients participated in a semi-structured interview in which they reviewed a description of a hypothetical RCT, were asked open-ended and focused follow-up questions regarding their motivations for and concerns about enrollment, and completed a questionnaire assessing characteristics such as demographics and prior knowledge of IMRT or PBT. Patients' stated WTP was assessed using a 6-point Likert scale. RESULTS: Forty-six eligible patients (33 white, 13 black) were enrolled from the practices of eight physicians. We identified 21 factors that impacted patients' WTP, which largely centered on five major themes: altruism/desire to compare treatments, randomization, deference to physician opinion, financial incentives, and time demands/scheduling. Most patients (27 of 46, 59%) stated they would either "definitely" or "probably" participate. Seventeen percent (8 of 46) stated they would "definitely not" or "probably not" enroll, most of whom (6 of 8) preferred PBT before their physician visit. CONCLUSIONS: A substantial proportion of patients indicated high WTP in a RCT comparing IMRT and PBT for PCa.

[Quality of life after radiotherapy for prostate cancer]. / Qualité de vie après radiothérapie pour un cancer localisé de la prostate.

The goal of localized prostate cancer radiotherapy is to cure patients. The decision-making must integrate the survival but also the quality of life of patients. Some French validated self-reported questionnaires are available to evaluate quality of life. Whatever the treatments (radical prostatectomy, brachytherapy, external beam radiation, with or without hormonotherapy), even if patients report more sequelae, their long-term quality of life is similar to that of the general population, except for patients treated with hormonotherapy who complain more decline of physical quality of life. In comparison with prostatectomy, patients treated with external beam radiation report less long-lasting urinary symptoms, but more bowel side effects, with no difference in global quality of life. Sexual disorders are initially less important with external beam radiation but increase over time. Brachytherapy shows no sexual function preservation benefit relative to radiation and may be less favourable with more urinary sequelae. The association of hormonotherapy and external beam radiation decreases the quality of life of the patients, with a negative impact on vitality, sexuality and increase urinary disorders. Intensity-modulated radiotherapy (IMRT) seems to better preserve the long-term digestive quality of life in comparison with conformal radiation therapy. Post-prostatectomy could induce more digestive toxicity, such as rectal irritation. The adjunction of hormonotherapy to radiation, the previous medical history of abdominal surgery, the field of radiation and the acute reactions to radiation are the main predictive factors to late toxicity and should be considered in the choice of initial treatment and for the follow-up.