Symptoms from treatment with sunitinib or sorafenib: a multicenter explorative cohort study to explore the influence of patient-reported outcomes on therapy decisions.

PURPOSE: Optimal long-lasting treatment with sunitinib and sorafenib is limited by dose modifications (DMs) due to adverse events (AEs). These AEs may be underrecognized and their influence on health-related quality of life (HRQL) underestimated. Improved insight into the relationship between AEs and therapy decisions is needed. To improve decision making around managing symptoms and reduce DMs, this study was set up to explore the influence of patient-reported symptoms on therapy decisions. METHODS: In this multicenter cohort study, patient characteristics, reasons for and different forms of used dose modifications, and AEs were prospectively obtained from cancer patients on sunitinib/sorafenib treatment. Used instruments to get insight into AEs were the patient-scored Utrecht Symptom Diary (USD) and the professional-scored Common Terminology Criteria for AEs version 3.0. RESULTS: Median total treatment duration in 42 patients was 16 weeks. Median time till dose modification was 10 weeks. DMs occurred mostly due to multiple mild AEs. By using the USD, a higher prevalence of most AEs was found compared to the literature. Sixty percent of the patients experienced a decreased HRQL due to multiple AEs. CONCLUSIONS: Because severe AEs due to sunitinib/sorafenib treatment seldom occur, it is more important to focus on treating and preventing multiple mild AEs with higher impact on HRQL, when trying to avoid dose modifications. Using patient self-reported measurement methods helps to early recognize symptoms and to differentiate among symptom intensities. This systematic approach might help to achieve the optimal dosing, which might improve PFS and OS.

Patient-reported outcome measures compared to clinician reported outcomes regarding incontinence and erectile dysfunction in localized prostate carcinoma after robot assisted radical prostatectomy: Impact on management.

PURPOSE/ BACKGROUND: Patient-reported outcome measures (PROMs) are widely used after robot assisted radical prostatectomy (RARP) in order to evaluate the impact/burden of the treatment. The most bothersome side effects of RARP are urine incontinence (UI) and erectile dysfunction (ED). During the follow up consultations, clinicians report these side effects in interviewing patients. Our study examined the discrepancy between the PROMs and clinician report outcomes (CROs) and hypothesized that the disagreement could have an impact on the management of UI and ED. METHODS: Up to 1 year after RARP, UI and ED recovery of 312 men with localized and locally advanced prostate cancer were assessed using the International Consultation Incontinence Questionnaire Short-Form (ICIQ-SF) and the International Index of Erectile Function (IIEF-EF) and CROs by interview. Discrepancies between PROs and CROs were studied in light of treatment offered and management. RESULTS: The ICIQ-SF Score matched with CROs in all sum score categories except in ICIQ sum score 6 to 12; here the UI was underreported by clinicians in 58% and 59% of patients at 8 and 12 months (P < 0.001). Furthermore, at 8 and 12 months postoperatively, clinicians underreported UI in 29% and 23% of patients with ICIQ score 13-18 (P < 0.001). The clinician significantly over-reported the recovery of erectile function ("normal erection") (P < 0.001), especially in men with IIEF-EF sum score 6 to 16. Independently of ICIQ-SF/IIEF-EF scores, discrepancy between PROs and CROs did not affect rate of health care offered to patients. CONCLUSIONS: This is to our knowledge the first study that compared the PROs with clinician reported functional outcomes and the impact of discrepancies on the management of side effects of RARP in prostate cancer. Observed discrepancies between the PROs and CROs did not affect offered management and counseling of UI and ED.

Functional outcomes rather than complications predict poor health-related quality of life at 6 months after robot-assisted radical prostatectomy.

The objective is to evaluate the effect of robot-assisted radical prostatectomy (RARP)-related postoperative complications on the 6-month postoperative health-related quality of life (HRQoL). A total of 1008 patients underwent a RARP with or without pelvic lymph node dissection (PLND) between 2012 and 2020 and were invited to complete questionnaires about HRQoL and functional outcomes (urinary incontinence (UI), erectile dysfunction (ED) and urinary complaints (UC)) before and 6 months after RARP. Patient characteristics and postoperative complications up to 90 days after surgery were prospectively recorded. Associations between complications and HRQoL/functional outcomes were assessed by multivariate linear regression analyses. In total, 528 patients (52.4%) were included in the analyses. Complications occurred in 165/528 (31.3%) patients, of which 30/165 (18.2%) had a Clavien-Dindo ≥ III complication. In multivariate regression analyses, postoperative complications were not significantly associated with postoperative HRQoL, UI and ED (p = 0.73, p = 0.72 and p = 0.95, respectively), but were significantly associated with a minor increase in UC (ß = 1.7, p < 0.001). More specifically, infectious and urological complications were significantly associated with an increase in UC (ß = 1.9, p < 0.001 and ß = 0.9, p = 0.004, respectively). The presence of UTI, in particular, was significantly associated with this minor increase (ß = 1.5, p = 0.002). Functional outcomes were all significantly associated with the HRQoL at 6 months postoperatively. No significant associations were found between postoperative complications and HRQoL at 6 months after RARP. However, worse functional outcomes were associated with a worse HRQoL at 6 months postoperatively. In addition, postoperative infectious and urological complications were significantly associated with a minor increase in UC.

A phase I, dose-finding study of sunitinib in combination with irinotecan in patients with advanced solid tumours.

BACKGROUND: Sunitinib is a multitargeted, oral tyrosine kinase inhibitor with antitumour and antiangiogenic activity. We investigated the safety and pharmacokinetics of sunitinib in combination with irinotecan in patients with advanced, refractory solid tumours. METHODS: Sunitinib was initially administered once daily at 37.5 mg per day on days 1-14 of a 21-day cycle, in which irinotecan 250 mg m(-2) was given on day 1. In a second cohort, the sunitinib dose was reduced to 25 mg per day. Blood samples were collected for pharmacokinetic studies. RESULTS: In the sunitinib 37.5 mg per day cohort, 3 out of 10 evaluable patients had objective responses, but dose-limiting toxicities (DLTs) of neutropenia, pneumococcal sepsis, and fatigue were observed. There were no DLTs in the sunitinib 25 mg per day cohort. Paired observations of pharmacokinetic parameter values of sunitinib and irinotecan alone vs the combination did not reveal significant drug-drug interactions. The maximum tolerated dose was defined as sunitinib 25 mg per day (days 1-14) with irinotecan 250 mg m(-2) (day 1), but no activity was observed at this dose. CONCLUSION: Although a higher sunitinib dose of 37.5 mg per day (days 1-14) with irinotecan showed preliminary evidence of antitumour activity, this dose was poorly tolerated. Therefore, this particular combination will not be pursued for further studies.

Cluster of serogroup W invasive meningococcal disease in a university campus.

INTRODUCTION: In France, the expansion of an hypervirulent strain causing serogroup W invasive meningococcal disease (MenW) has been observed since 2015/16. We describe a cluster of three MenW cases, causing two deaths, at the end of 2016 in a university campus, and the vaccination campaign which was consequently organized. METHODS: Epidemiological and microbiological analyses led a multidisciplinary expertise group to recommend the organization of a mass vaccination campaign using ACWY vaccine targeting more than 30,000 students and staff in the university campus. Individual data on vaccination was collected using the lists of students and staff registered at the university to estimate vaccine coverage. RESULTS: Three MenW cases occurred within a 2-month period among students in different academic courses. All three isolates were identical and belonged to the "UK-2013 strain" phylogenetic branch. The attack rate was 10.8/100,000 students. The vaccination campaign was organized only 15 days after the third case occurred. In total, 13,198 persons were vaccinated. Vaccine coverage was estimated at 41% for students of the university and 35% for university staff. CONCLUSION: Timely notification of cases to health authorities was essential for the detection of the cluster and the rapid implementation of the vaccination campaign. No further cases occurred in the campus in the year following the vaccination campaign. This episode is the second cluster of MenW caused by the "UK-2013 strain" in a university since 2016.

A prediction model relating the extent of intraoperative fascia preservation to erectile dysfunction after nerve-sparing robot-assisted radical prostatectomy.

Robot-assisted radical prostatectomy (RARP) is performed in patients with prostate cancer. Unfortunately, 10-46% of patients may still suffer from limited erectile function (EF) after RARP. This study aimed to develop a prediction model based on the extent of fascia preservation (FP) and postoperative EF after RARP. A previously developed FP score quantizing the extent and regions of nerve-preservation was determined in a cohort of 1241 patients who underwent RARP. The predictive value of the FP score for post-prostatectomy EF (following the international index erectile function (IIEF) score, EF domain) was analyzed. To increase the predictive value of the scoring system, the FP regions were related to postoperative EF, nerve distribution and co-morbidity factors. Finally, a prediction model for EF was developed based on the studied cohort. When corrected for the preoperative IIEF-EF, the FP score was shown to be a significant denominator for IIEF (p = 2.5 × 10- 15) with an R2 of 35%. Variable selection performed using the Akaike information criterion led to a final prediction model for postoperative IIEF after nerve-preservation based on the FP score. Furthermore, patient's age, preoperative IIEF score, CCIS and use of clips for nerve sparing were significantly associated with postoperative IIEF-EF. More anterior fascia preservation was correlated with better EF outcome and age was a strong independent predictor of EF outcome. In older men, the relative benefit of more extensive fascia preservation was at least similar to younger men, despite a lower baseline IIEF-EF score. Quantitative nerve-sparing FP scoring could be related to the postoperative IIEF-EF and integrated into a multivariate prediction model, which includes with age, use of surgical clips, the Charlson Comorbidity Index Score (CCIS), and preoperative IIEF-EF. When further validated the prediction model could provide patients and care-givers a qualitative estimation of EF outcome after RARP.

Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer.

Sunitinib has been registered for the treatment of advanced renal cell cancer (RCC). As patient inclusion was highly selective in previous studies, experience with sunitinib in general oncological practice remains to be reported. We determined the efficacy and safety of sunitinib in patients with advanced RCC included in an expanded access programme. ECOG performance status >1, histology other than clear cell and presence of brain metastases were no exclusion criteria. Eighty-two patients were treated: 23% reached a partial response, 50% had stable disease, 20% progressed and six patients were not evaluable. Median progression-free survival (PFS) was 9 months and median overall survival (OS) was 15 months. Importantly, 47 patients (57%) needed a dose reduction, 35 (43%) because of treatment-related adverse events, 10 (12%) because of continuous dosing, and two because of both. Stomatitis, fatigue, hand-foot syndrome and a combination of grade 1-2 adverse events were the most frequent reasons for dose reduction. In 40 patients (49%), there was severe toxicity, defined as dose reduction or permanent discontinuation, which was highly correlated with low body surface area, high age and female gender. On the basis of age and gender, a model was developed that could predict the probability of severe toxicity.

Vesico-urethral anastomosis (VUA) evaluation of short- and long-term outcome after robot-assisted laparoscopic radical prostatectomy (RARP): selective cystogram to improve outcome.

The role of a cystogram to assess the vesico-urethral anastomosis (VUA) after robot-assisted laparoscopic radical prostatectomy (RARP) has been debated. Early catheter removal without cystogram was reported to be associated with a trend towards an increased risk of acute urinary retention (AUR). In two cohorts we studied the effects of VUA leakage on cystogram and functional outcome after RARP. Cohort A contained 1390 consecutive men that routinely underwent a cystogram after RARP. Transurethral catheter (TUC) was removed in the absence of VUA leakage or minimal leakage on subsequent repeat cystogram. Outcome was compared to a group of 120 men that underwent cystography 7-10 days after RARP but had the TUC removed independent of cystography findings (cohort B). Outcome was assessed by early clinical follow-up and quality of life (QOL) questionnaires at 6 months. Men in cohort B had an increased risk of AUR and 6 months voiding complaints when compared to cohort A. The incidence of AUR and voiding complaints was associated with grade 2-3 leakage on cystography in cohort B but not in cohort A. Grade 2-3 leakage on cystogram was more likely in men with larger prostates larger and preoperative voiding complaints. Selective cystogram in men with larger prostates and preoperative lower urinary tract symptoms (LUTS) may prevent early AUR and voiding complaints after RARP when prolonged TUC use is applied.

Clinical value of serum glycoprotein galactosyltransferase levels in different histological types of ovarian carcinoma.

Serum glycoprotein galactosyltransferase levels were determined in 28 healthy women and 113 patients with ovarian carcinoma with various histological types, at different clinical stages. Ovomucoid, which possesses terminal N-acetylglucosaminyl residues, was used as glycoprotein acceptor. Clinical correlations between galactosyltransferase levels and tumor burden were examined, as well as the variations due to histology. Follow-up studies could be done for 60 patients, and correlations with clinical evolution, established. Galactosyltransferase might be a promising marker for the diagnosis and follow-up of ovarian carcinomas.

Short-term health effects of an industrial toxic waste landfill: a retrospective follow-up study in Montchanin, France.

A retrospective follow-up study was conducted in 1990 to assess the short-term health impacts of an industrial waste landfill. The site, located since 1979 in a French town of 6,000 inhabitants (about 100 m from the nearest houses) released volatile organic compounds (VOCs) into the air and provoked intense health concern in the community. The landfill was subsequently closed in 1988. Subjects were 694 inhabitants residing in three different parts of town. Individual exposure was estimated, using a dispersion model of volatile air pollutants and accommodated the daily activity patterns of each individual within the area under investigation. Surrogate morbidity data were derived from measurement of the consumption of drugs prescribed for specific therapeutic categories over a 3-y period (18 mo before and 18 mo after the site was closed). Although differences were not statistically significant, the most exposed subjects had been prescribed more drugs for diseases possibly linked to emissions from the site before it closed than the least exposed individuals. There was a suggestion of a slight trend in the consumption of drugs for ear, nose, and throat and pulmonary ailments with individual exposure levels. These results, and the review of toxicological data for some of the VOCs released by the dump, support the decision to close the site.

Case-control assessment of the short-term health effects of an industrial toxic waste landfill.

An industrial waste landfill located within a residential area received 400,000 tons of toxic wastes between 1980 and mid 1988, in Montchanin, France. Triggered by odor nuisances caused by emissions of volatile organic compounds (VOCs), an intense local community concern led to the decision to close the site. A physician's practice-based case-control study was conducted in order to evaluate the short-term health impact of the remaining VOC emissions. Eight hundred and sixteen questionnaires were collected, divided into 432 cases (patients with conditions associated with the dump emissions) and 384 controls (other patients). Individual exposure was assessed using a combination of statistical modeling of airborne toxicants along with the determination of the time-activity patterns of the subjects throughout the study area. After adjustment for confounding factors (age, smoking, alcohol consumption, date of moving to town), nonspecific irritative respiratory symptoms occurred more frequently among the exposed subjects, with a positive trend across the three exposure categories [OR1 = 1.54; 95% CI = (0.69-3.41), OR2 = 2.09 (1.0-4.38)], and appeared to be related to long-lasting (prevalent) conditions. Psychiatric disorders were also found to be related to the exposure indexes [OR1 = 2.1 (1.01-4.37); OR2 = 2.52 (1.21-5.26)], but this association could be biased by the negative perception of the waste site. Similar findings were described in other toxic waste site-related studies.