Results from the UNITED study: a multicenter study validating the prognostic effect of the tumor-stroma ratio in colon cancer.

BACKGROUND: The TNM (tumor-node-metastasis) Evaluation Committee of Union for International Cancer Control (UICC) and College of American Pathologists (CAP) recommended to prospectively validate the cost-effective and robust tumor-stroma ratio (TSR) as an independent prognostic parameter, since high intratumor stromal percentages have previously predicted poor patient-related outcomes. PATIENTS AND METHODS: The 'Uniform Noting for International application of Tumor-stroma ratio as Easy Diagnostic tool' (UNITED) study enrolled patients in 27 participating centers in 12 countries worldwide. The TSR, categorized as stroma-high (>50%) or stroma-low (≤50%), was scored through standardized microscopic assessment by certified pathologists, and effect on disease-free survival (DFS) was evaluated with 3-year median follow-up. Secondary endpoints were benefit assessment of adjuvant chemotherapy (ACT) and overall survival (OS). RESULTS: A total of 1537 patients were included, with 1388 eligible stage II/III patients curatively operated between 2015 and 2021. DFS was significantly shorter in stroma-high (n = 428) than in stroma-low patients (n = 960) (3-year rates 70% versus 83%; P < 0.001). In multivariate analysis, TSR remained an independent prognosticator for DFS (P < 0.001, hazard ratio 1.49, 95% confidence interval 1.17-1.90). As secondary outcome, DFS was also worse in stage II and III stroma-high patients despite adjuvant treatment (3-year rates stage II 73% versus 92% and stage III 66% versus 80%; P = 0.008 and P = 0.011, respectively). In stage II patients not receiving ACT (n = 322), the TSR outperformed the American Society of Clinical Oncology (ASCO) criteria in identifying patients at risk of events (event rate 21% versus 9%), with a higher discriminatory 3-year DFS rate (stroma-high 80% versus ASCO high risk 91%). A trend toward worse 5-year OS in stroma-high was noticeable (74% versus 83% stroma-low; P = 0.102). CONCLUSION: The multicenter UNITED study unequivocally validates the TSR as an independent prognosticator, confirming worse outcomes in stroma-high patients. The TSR improved current selection criteria for patients at risk of events, and stroma-high patients potentially experienced chemotherapy resistance. TSR implementation in pathology diagnostics and international guidelines is highly recommended as aid in personalized treatment.

The value of post-operative chemotherapy after chemoradiotherapy in patients with high-risk locally advanced rectal cancer-results from the RAPIDO trial.

BACKGROUND: Pre-operative chemoradiotherapy (CRT) rather than radiotherapy (RT) has resulted in fewer locoregional recurrences (LRRs), but no decrease in distant metastasis (DM) rate for patients with locally advanced rectal cancer (LARC). In many countries, patients receive post-operative chemotherapy (pCT) to improve oncological outcomes. We investigated the value of pCT after pre-operative CRT in the RAPIDO trial. PATIENTS AND METHODS: Patients were randomised between experimental (short-course RT, chemotherapy and surgery) and standard-of-care treatment (CRT, surgery and pCT depending on hospital policy). In this substudy, we compared curatively resected patients from the standard-of-care group who received pCT (pCT+ group) with those who did not (pCT- group). Subsequently, patients from the pCT+ group who received at least 75% of the prescribed chemotherapy cycles (pCT ≥75% group) were compared with patients who did not receive pCT (pCT-/- group). By propensity score stratification (PSS), we adjusted for the following unbalanced confounders: age, clinical extramural vascular invasion, distance to the anal verge, ypT stage, ypN stage, residual tumour, serious adverse event (SAE) and/or readmission within 6 weeks after surgery and SAE related to pre-operative CRT. Cumulative probability of disease-free survival (DFS), DM, LRR and overall survival (OS) was analysed by Cox regression. RESULTS: In total, 396/452 patients had a curative resection. The number of patients in the pCT+, pCT >75%, pCT- and pCT-/- groups was 184, 112, 154 and 149, respectively. The PSS-adjusted analyses for all endpoints demonstrated hazard ratios between approximately 0.7 and 0.8 (pCT+ versus pCT-), and 0.5 and 0.8 (pCT ≥75% versus pCT-/-). However, all 95% confidence intervals included 1. CONCLUSIONS: These data suggest a benefit of pCT after pre-operative CRT for patients with high-risk LARC, with approximately 20%-25% improvement in DFS and OS and 20%-25% risk reductions in DM and LRR. Compliance with pCT additionally reduces or improves all endpoints by 10%-20%. However, differences are not statistically significant.

Vaginal changes, sexual functioning and distress of women with locally advanced cervical cancer treated in the EMBRACE vaginal morbidity substudy.

OBJECTIVE: The EMBRACE-vaginal morbidity substudy prospectively evaluated physician-assessed vaginal changes and patient-reported-outcomes (PRO) on vaginal and sexual functioning problems and distress in the first 2-years after image-guided radio(chemo)therapy and brachytherapy for locally advanced cervical cancer. METHODS: Eligible patients had stage IB1-IIIB cervical cancer with ≤5 mm vaginal involvement. Assessment of vaginal changes was graded using CTCAE. PRO were assessed using validated Quality-of-Life and sexual questionnaires. Statistical analysis included Generalized-Linear-Mixed-Models and Spearman's rho-correlation coefficients. RESULTS: 113 eligible patients were included. Mostly mild (grade 1) vaginal changes were reported over time in about 20% (range 11-37%). At 2-years, 47% was not sexually active. Approximately 50% of the sexually active women reported any vaginal and sexual functioning problems and distress over time; more substantial vaginal and sexual problems and distress were reported by up to 14%, 20% and 8%, respectively. Physician-assessed vaginal changes and PRO sexual satisfaction differed significantly (p ≤ .05) between baseline and first follow-up, without further significant changes over time. No or only small associations between physician-assessed vaginal changes and PRO vaginal functioning problems and sexual distress were found. CONCLUSIONS: Mild vaginal changes were reported after image-guided radio(chemo)therapy and brachytherapy, potentially due to the combination of tumors with limited vaginal involvement, EMBRACE-specific treatment optimization and rehabilitation recommendations. Although vaginal and sexual functioning problems and sexual distress were frequently reported, the rate of substantial problems and distress was low. The lack of association between vaginal changes, vaginal functioning problems and sexual distress shows that sexual functioning is more complex than vaginal morbidity alone.

Pelvic floor physical therapy in patients with chronic anal fissure: long-term follow-up of a randomized controlled trial.

BACKGROUND: Chronic anal fissure is a common benign anorectal disease with a high recurrence rate. Pelvic floor physical therapy has been proven effective in the short-term management in patients with chronic anal fissure and pelvic floor dysfunction (PAF-trial). The aim of this study was to determine the outcomes of the PAF-trial and fissure recurrence in patients who completed the 2 months of pelvic floor physical therapy at 1-year follow-up. METHODS: Electromyographic registration of the pelvic floor, digital rectal examination, visual analog scales, patient-related outcome measurements, and quality of life were assessed at baseline and at 1-year after inclusion. The primary outcome was muscle tone at rest during electromyographic registration of the pelvic floor at baseline and at 1-year follow-up. Secondary outcomes contained fissure recurrence, pain ratings, pelvic floor dysfunction, complaint reduction measured with a proctology specific patient-reported outcome measurement, and quality of life. RESULTS: The treatment protocol was followed by 137 patients. Ninety-seven patients (71%) completed the 1-year follow-up, 48 women (49.5%) and 49 men (50.5%) with a mean age of 44.4 ± 11.6 years (range 19-68). In the total group of patients, mean resting electromyographic values of the pelvic floor significantly improved from baseline to follow-up at 1 year (mean estimated difference 2.20 µV; 95% CI, 1.79 to 2.61; p < 0.001). After 1 year, the fissure recurred in 15 patients (15.5%). VAS-pain significantly decreased from baseline to follow-up (mean estimated difference 4.16; 95% CI, 3.75 to 4.58; p < 0.001). Dyssynergia was found in 72.9% at baseline and decreased to 14.4% at 1-year follow-up (p < 0.001). Complaint reduction measured with the Proctoprom significantly improved from baseline to 1-year follow-up (p < 0.001). Quality of life (RAND-36) significantly improved in eight of nine domains at 1-year follow-up. No significant improvement was found in the domain vitality. CONCLUSIONS: In the PAF-trial, we demonstrated that pelvic floor physical therapy yields a significant and clinical benefit in the time course and therefore should be advocated as adjuvant conservative treatment in patients with chronic anal fissure. TRIAL REGISTRATION: The trial is registered at the Dutch Trial registry (NTR7581)  https://trialsearch.who.int.

Pelvic floor physical therapy in the treatment of chronic anal fissure (PAF trial): quality of life outcome.

BACKGROUND: Chronic anal fissure is one of the most common anorectal diseases and is associated with reduced quality of life. The aim of this study was to investigate the effects of pelvic floor physical therapy on quality of life in patients with chronic anal fissure using the Short-Form 36 Health Survey (RAND-36). METHODS: Adult patients, with chronic anal fissure and concomitant pelvic floor dysfunction, such as dyssynergia and increased pelvic floor muscle tone, were recruited at the Proctos Clinic in the Netherlands, between December 2018 and July 2021 and randomly assigned to an intervention group, receiving 8 weeks of pelvic floor physical therapy or assigned to a control group receiving postponed pelvic floor physical therapy (PAF trial). Quality of life and pain ratings were outcomes of the study and were measured at 8- and 20-week follow-up. RESULTS: One hundred patients (50 women and 50 men, median age 44.6 years [range 19-68 years]), completed the RAND-36 questionnaire and visual analog (VAS) pain scale score at admission. A significant improvement was found at 20-week follow-up in all domains of the RAND-36; physical functioning, pain, health change (p < 0.001); physical role, vitality, general health, social functioning, emotional role, mental health (p < 0.05). VAS pain was significantly reduced at 8 weeks (mean estimated difference 1.98; 95% CI 1.55-2.42, p < 0.001) and remained significant at 20-week follow-up (p < 0.001). The difference between the groups as regards change in the mean pain intensity scores at 8 weeks was 2.48 (95% CI - 3.20 to - 1.75; p < 0.001). Compared to the reference values of the general Dutch population, the patients in our study with a chronic anal fissure and pelvic floor dysfunction reported an impaired quality of life in 8 of 9 domains of the RAND-36. After treatment, significant lower scores were found in 2 out of 9 domains. CONCLUSIONS: The results of this study provide evidence that treatment by pelvic floor physical therapy improves quality of life and reduces pain, making it an important tool in management of chronic anal fissure and concomitant pelvic floor dysfunction.

An Educational Need Regarding Treatment-Related Infertility and Fertility Preservation: a National Survey Among Members of the Dutch Society for Medical Oncologists.

Cancer diagnosis and treatment may influence reproductive planning and impact fertility in patients of reproductive age. Although guidelines have been established in the past decade, education, practice, and attitudes of medical oncologists regarding fertility preservation remain undecided. A nationwide survey was performed among members of the Dutch Society for Medical Oncology. Demographics, practice, knowledge, and barriers were measured regarding information provision of fertility preservation towards cancer patients of childbearing age. From 392 members, 120 oncologists completed the questionnaire (30.6%). Majority of oncologists was convinced it is their responsibility to discuss impact of cancer treatment to fertility (93.2%), yet 68.3% discussed the subject often or always (n = 82). Oncologists employed in district general hospitals were less likely to discuss fertility (p = 0.033). On average, 44.6% of reproductive men and 28.9% of reproductive women is referred to fertility specialists. Half of the respondents declared to possess sufficient knowledge regarding fertility preservation (n = 57, 47.5%). Poor prognosis (53%), unlikely survival (43.1%), and high chances on fertility recovery (28.7%) were identified as barriers to discussing fertility preservation. Among oncologists, impact of cancer treatment on fertility is a well-accepted responsibility to counsel. Despite, self-reported knowledge regarding fertility preservation is strongly varying. In practice, fertility is discussed to some extent, influenced by several barriers and depending on prognosis and type of hospital. Patients benefit from knowledge improvement among oncology care providers concerning fertility effects of cancer treatment. Education during medical school, residency, and among practicing oncologists may raise awareness, together with enhancement of referral possibilities.

Sublingual Sufentanil versus Standard-of-Care (Patient-Controlled Analgesia with Epidural Ropivacaine/Sufentanil or Intravenous Morphine) for Postoperative Pain Following Pancreatoduodenectomy: A Randomized Trial.

Background: The optimal treatment strategy for postoperative pain following pancreatoduodenectomy remains unknown. The aim of this study was to investigate whether sublingual sufentanil tablet (SST) is a non-inferior analgesic compared to our standard-of-care (patient-controlled epidural analgesia [PCEA] or PCA morphine) in the treatment of pain following pancreatoduodenectomy. Methods: This was a pragmatic, strategy, open-label, non-inferiority, parallel group, randomized (1:1) trial. The primary outcome was an overall mean pain score (Numerical Rating Scale: 0-10) on postoperative days 1 to 3 combined. The non-inferiority margin was -1.5 since this difference was considered clinically relevant. Results: Between October 2018 and July 2021, 190 patients were assessed for eligibility and 36 patients were included in the final analysis: 17 patients were randomized to SST and 19 patients to standard-of-care. Early treatment failure in the SST group occurred in 2 patients (12%) due to inability to operate the SST system and in 2 patients (12%) due to severe nausea despite antiemetics. Early treatment failure in the standard-of-care group occurred in 2 patients (11%) due to preoperative PCEA placement failure and in 1 patient (5%) due to hemodynamic instability caused by PCEA. The mean difference in pain score on postoperative day 1 to 3 was -0.10 (95% CI -0.72-0.52), and therefore the non-inferiority of SST compared to standard-of-care was demonstrated. The mean pain score, number of patients reporting unacceptable pain (pain score >4), Overall Benefit of Analgesia Score, and patient satisfaction per postoperative day, perioperative hemodynamics and postoperative outcomes did not differ significantly between groups. Conclusion: This first randomized study investigating the use of SST in 36 patients following pancreatoduodenectomy showed that SST is non-inferior compared to our standard-of-care in the treatment of pain on postoperative days 1 to 3. Future research is needed to confirm that these findings are applicable to other settings.

Pelvic floor physical therapy in patients with chronic anal fissure: a randomized controlled trial.

BACKGROUND: A chronic anal fissure is a common, painful condition with great impact on daily life. The exact pathogenesis has not been fully elucidated and treatment varies. A large percentage of patients experience pelvic floor dysfunction (dyssynergia and increased pelvic floor muscle tone). The aim of our study was to investigate the effect of pelvic floor physical therapy in patients with chronic anal fissure. METHODS: Between December 2018 and July 2021, at the Proctos Clinic in the Netherlands, patients with chronic anal fissure and pelvic floor dysfunction were randomly assigned to an intervention group, receiving 8 weeks of pelvic floor physical therapy including electromyographic biofeedback or assigned to a control group receiving postponed pelvic floor physical therapy. The primary outcome was muscle tone at rest during electromyographic registration of the pelvic floor before and after pelvic floor physical therapy. Secondary outcomes contained healing of the fissure, pain ratings, improvement of pelvic floor function, and complaint reduction measured with a proctology-specific patient-reported outcome measurement. Endpoints were measured at 8- and 20-week follow-up. RESULTS: One hundred forty patients were included in the study, 68 men (48.6%) and 72 women (51.4%) with a mean age of 44.5 ± 11.1 (range 19-79) years. Mean resting electromyographic values of the pelvic floor in the intervention group significantly improved from pre- to post-treatment (p < 0.001) and relative to controls (mean estimated difference between groups - 1.88 µV; 95% CI, - 2.49 to - 1.27 (p < 0.001) at first follow-up and remained significant from baseline at 20-week follow-up (p < 0.001). The intervention group performed better compared to the control group on all secondary outcomes, i.e., healing of the fissure (55.7% of the patients vs 21.4% in control, pain ratings (p < 0.001), diminished dyssynergia (p < 0.001), complaint reduction (p < 0.001), and decrease of pelvic floor muscle tone (p < 0.05) at first follow-up. CONCLUSIONS: The findings of this study provide strong evidence that pelvic floor physical therapy is effective in patients with chronic anal fissure and pelvic floor dysfunction and supports its recommendation as adjuvant treatment besides regular conservative treatment.

Efficacy and safety of durvalumab with olaparib in metastatic or recurrent endometrial cancer (phase II DOMEC trial).

BACKGROUND: Patients with advanced endometrial cancer have a poor prognosis, and treatment options are limited. The investigator-initiated, multicenter, phase II DOMEC trial (NCT03951415) is the first trial to report data on efficacy and safety of combined treatment with PD-L1 and PARP inhibition for advanced endometrial cancer. PATIENTS AND METHODS: Patients with metastatic or recurrent endometrial cancer were enrolled. Patients received durvalumab 1500 mg intravenously q4w and olaparib 300 mg 2dd until disease progression, unacceptable toxicity, or patient withdrawal. Patients with at least 4 weeks of treatment were evaluable for analysis. The primary endpoint was progression-free survival at 6 months. Evidence for efficacy was defined as progression-free survival at 6 months in ≥50% of patients. Secondary endpoints included safety, objective response and overall survival. RESULTS: From July 2019, through November 2020, 55 patients were enrolled. At data cut-off (September 2021), 4 of the 50 evaluable patients were still on treatment. Seventeen patients (34%) were progression-free at 6 months. Objective response rate was 16% (95% CI, 8.3 to 28.5) with 1 complete and 7 partial responses. With a median follow-up of 17.6 months, median progression-free survival was 3.4 months (95% CI, 2.8 to 6.2) and median overall survival was 8.0 months (95% CI, 7.5 to 14.3). Grade 3 treatment-related adverse events occurred in 8 patients (16%), predominantly anemia. There were no grade 4 or 5 treatment-related adverse events. CONCLUSION: The combination of durvalumab and olaparib was well tolerated, but did not meet the prespecified 50% 6-month progression-free survival in this heterogeneous patient population with advanced endometrial cancer.

Sexual and fertility-related adverse effects of medicinal treatment for cancer; a national evaluation among medical oncologists.

BACKGROUND: Anti-cancer drugs commonly adversely affect fertility and sexual function. Despite this, patients report a lack of counselling of these potential adverse effects. The aim was to determine Dutch oncologists' knowledge about the adverse effects of various cancer drugs on fertility and sexual function. METHODS: A cross-sectional survey was sent to members of the Dutch Society for Medical Oncology (n = 433). The survey questions included various cancer drugs' adverse effects on fertility, ovulation, spermatogenesis, and sexual function. RESULTS: One hundred and five of 392 oncologists responded (26.8%). Oncologists were more aware of the adverse effects on fertility compared to sexual function. Drugs that were mostly believed to negatively affect fertility were cisplatin (n = 81, 80.2%), epirubicin (n = 78, 78.0%) and cyclophosphamide (n = 80, 77.7%). Regarding sexual function, most mentioned drugs were tamoxifen (n = 67, 65.7%), GnRH-agonists (n = 64, 63.4%) and cisplatin (n = 58, 57.4%). Oncologists with expertise in urology possessed more awareness regarding sexuality-related adverse effects (cisplatin p = 0.038, etoposide p = 0.025, ifosfamide p = 0.06, vinblastine p = 0.000). CONCLUSION: Results revealed that oncologists have different beliefs about possible sexual and fertility-related adverse effects concerning medication resources and literature. Based on our results, oncologists do not possess sufficient knowledge to inform patients about sexual and fertility-related adverse effects.

A genetically defined signature of responsiveness to erlotinib in early-stage pancreatic cancer patients: Results from the CONKO-005 trial.

BACKGROUND: high recurrence rates of up to 75% within 2 years in pancreatic ductal adenocarcinoma (PDAC) patients resected for cure indicate a high medical need for clinical prediction tools and patient specific treatment approaches. Addition of the EGFR inhibitor erlotinib to adjuvant chemotherapy failed to improve outcome but its efficacy in some patients warrants predictors of responsiveness. PATIENTS AND METHODS: we analysed tumour samples from 293 R0-resected patients from the randomized, multicentre phase III CONKO-005 trial (gemcitabine ± erlotinib) with targeted sequencing, copy number, and RNA expression analyses. FINDINGS: a total of 1086 mutations and 4157 copy-number aberrations (CNAs) with a mean of 17.9 /tumour were identified. Main pathways affected by genetic aberrations were the MAPK-pathway (99%), cell cycle control (92%), TGFß signalling (77%), chromatin remodelling (71%), and the PI3K/AKT pathway (65%). Based on genetic signatures extracted with non-negative matrix factorization we could define five patient clusters, which differed in mutation patterns, gene expression profiles, and survival. In multivariable Cox regression analysis, SMAD4 aberrations were identified as a negative prognostic marker in the gemcitabine arm, an effect that was counteracted when treated with erlotinib (DFS: HR=1.59, p = 0.016, and OS: HR = 1.67, p = 0.014). Integration of differential gene expression analysis established SMAD4 alterations with low MAPK9 expression (n = 91) as a predictive biomarker for longer DFS (HR=0.49; test for interaction, p = 0.02) and OS (HR = 0.32; test for interaction, p = 0.001). INTERPRETATION: this study identified five biologically distinct patient clusters with different actionable lesions and unravelled a previously unappreciated association of SMAD4 alteration status with erlotinib effectiveness. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that SMAD4 status might guide addition of erlotinib treatment in early-stage PDAC patients.

Caffeine Consumption and Behavioral Symptoms in Nursing Home Residents: A Cross-Sectional Analysis.

OBJECTIVE: Although behavioral changes are common in nursing home residents with dementia and caffeine is known to influence behavior in healthy adults, the effects of caffeine on the behavior of persons with dementia has received little attention. In this study we assessed the relationship of caffeine and behavioral symptoms in older persons with dementia. DESIGN: A multicenter sub-cohort study embedded in the Elderly Care Physicians (ECP) training program. SETTING: Dutch nursing homes associated with the ECP training program. PARTICIPANTS: A total of 206 individuals with both diabetes and dementia resident in Dutch nursing homes. MEASUREMENTS: Trainee ECPs collected data on caffeine consumption, cognition and behavioral symptoms using the NPI-NH, MDS-DRS and AES-C. Data on factors known to influence behavior in persons with dementia (e.g. marital status, kidney function, urinary tract infection and medication) were also collected. RESULTS: Of the 206 participants, 70% showed behavioral symptoms. An increase in caffeine consumption was associated with a decrease in the presence of behavioral symptoms in the NPI-NH cluster affect and NPI-NH item agitation. Caffeine consumption groups also differed on the presence of disinhibition and depression. In addition, the severity of dementia influenced agitation, anxiety and the clusters affect and psychomotor. CONCLUSION: In a large group of older persons with dementia resident in nursing homes, a low daily consumption of caffeine was associated with greater behavioral symptoms.

Adjuvant chemotherapy is superior to chemoradiation after D2 surgery for gastric cancer in the per-protocol analysis of the randomized CRITICS trial.

BACKGROUND: The Intergroup 0116 and the MAGIC trials changed clinical practice for resectable gastric cancer in the Western world. In these trials, overall survival improved with post-operative chemoradiotherapy (CRT) and perioperative chemotherapy (CT). Intention-to-treat analysis in the CRITICS trial of post-operative CT or post-operative CRT did not show a survival difference. The current study reports on the per-protocol (PP) analysis of the CRITICS trial. PATIENTS AND METHODS: The CRITICS trial was a randomized, controlled trial in which 788 patients with stage Ib-Iva resectable gastric or esophagogastric adenocarcinoma were included. Before start of preoperative CT, patients from the Netherlands, Sweden and Denmark were randomly assigned to receive post-operative CT or CRT. For the current analysis, only patients who started their allocated post-operative treatment were included. Since it is uncertain that the two treatment arms are balanced in such PP analysis, adjusted proportional hazards regression analysis and inverse probability weighted analysis were used to minimize the risk of selection bias and to estimate and compare overall and event-free survival. RESULTS: Of the 788 patients, 478 started post-operative treatment according to protocol, 233 (59%) patients in the CT group and 245 (62%) patients in the CRT group. Patient and tumor characteristics between the groups before start of the post-operative treatment were not different. After a median follow-up of 6.7 years since the start of post-operative treatment, the 5-year overall survival was 57.9% (95% confidence interval: 51.4% to 64.3%) in the CT group versus 45.5% (95% confidence interval: 39.2% to 51.8%) in the CRT group (adjusted hazard ratio CRT versus CT: 1.62 (1.24-2.12), P = 0.0004). Inverse probability weighted analysis resulted in similar hazard ratios. CONCLUSION: After adjustment for all known confounding factors, the PP analysis of patients who started the allocated post-operative treatment in the CRITICS trial showed that the CT group had a significantly better 5-year overall survival than the CRT group (NCT00407186).

The BUSCOPAN study: a randomized-controlled non-inferiority trial of a continuous butylscopolamine infusion versus placebo in patients with a renal colic not responding to oral non-steroidal anti-inflammatory drugs.

PURPOSE: To investigate whether placebo is non-inferior to continuous infusion of butylscopolamine in patients with renal colic. METHODS: We conducted a placebo-controlled, multicenter, double-blind randomized clinical trial (RCT) including 128 patients with renal colic (confirmed by ultrasound or CT-scan). Patients were randomized to receive either continuous IV butylscopolamine 100 mg/24 h or placebo (saline). Primary outcome is the amount of opioid escape medication used, measured in doses administered. Secondary outcomes are pain measured on a Numeric Rating Scale (NRS), side effects, and time of drug administration. Non-inferiority was assessed using linear regression with robust standard errors, with non-inferiority limit set at 0.5 units of escape medication. RESULTS: Median number of doses of escape medication was one in both groups. The number of extra doses in the placebo group compared with the butylscopolamine group was 0.05, with a 95% robust confidence interval (CI) of 0.38-0.47. Upper limit of the CI remained below the non-inferiority limit of 0.5 (p = 0.04). No differences in secondary endpoints were seen between the groups. CONCLUSION: Placebo is non-inferior to continuous IV butylscopolamine for pain relief in patients with renal colic. Based on this study and previous evidence, there is no role for continuous butylscopolamine IV in the treatment of renal colic. Trial NL7819.

Using a quality of life (QoL)-monitor: preliminary results of a randomized trial in Dutch patients with early breast cancer.

PURPOSE: The diagnosis and treatment of cancer negatively affect patients' physical, functional and psychological wellbeing. Patients' needs for care cannot be addressed unless they are recognized by healthcare providers (HCPs). The use of quality of life (QoL) assessments with feedback to HCPs might facilitate the identification and discussion of QoL-topics. METHODS: 113 patients with stage I-IIIB breast cancer treated with chemotherapy were included in this randomized controlled trial. Patients were randomly allocated to receive either usual care, or usual care with an intervention consisting of a QoL-monitor assessing QoL, distress and care needs before every chemotherapy cycle visit. Patients completed questionnaires regarding QoL, illness perceptions, self-efficacy, and satisfaction with communication. From the 2nd visit onwards, patients in the intervention arm and their HCPs received a copy of the QoL overview and results were shown in patients' medical files. Audio-recordings and patients' self-reports were used to investigate effects on communication, patient management and patient-wellbeing. A composite score for communication was calculated by summing the number of QoL-topics discussed during each consultation. RESULTS: Use of the QoL-monitor resulted in a higher communication score (0.7 topics increase per visit, p = 0.04), especially regarding the disease-specific and psychosocial issues (p < 0.01). There were no differences in patient management, QoL, illness perceptions or distress. Patients in the experimental arm (n = 60) had higher scores on satisfaction with communication (p < 0.05). CONCLUSIONS: Use of a QoL-monitor during chemotherapy in patients with early breast cancer might result in a more frequent discussion of QoL-topics, associated with high levels of patients' satisfaction.