App-based assessment of patient-reported outcomes in the Molecular Tumor Board in the Center for Personalized Medicine-(TRACE).

Background: Biomarker-based therapies are increasingly used in cancer patients outside clinical trials. Systematic assessment of patient-reported outcomes (PRO) is warranted to take patients' perspectives during biomarker-based therapies into consideration. We assessed the feasibility of an electronic PRO assessment via a smartphone application. Methods: An interdisciplinary expert panel developed a smartphone application based on symptom burden and health-related quality of life (HRQoL) metrics reported in a retrospective analysis of 292 neuro-oncological patients. The app included validated assessments of health-related quality of life (HRQoL), the burden of symptoms, and psychological stress. Feasibility and usability were tested in a pilot study. Semi-structured interviews with patients and health care professionals (HCP) were conducted, transcribed, and analyzed according to Mayring´s qualitative content analysis. Furthermore, we assessed compliance and descriptive data of ePROs. Results: A total of 14 patients have been enrolled, (9 female, 5 male). A total of 4 HCPs, 9 patients, and 1 caregiver were interviewed regarding usability/feasibility. The main advantages were the possibility to complete questionnaires at home and comfortable implementation in daily life. Compliance was high, for example, 82% of the weekly distributed NCCN distress thermometer questionnaires were answered on time, however, with interindividual variability. We observed a median distress score of 5 (range 0-10, 197 results, n = 12, weekly assessed) and a median Global health score of 58.3 according to the EORTC QLQ-C30 instrument (range 16.7-100, 77 results, n = 12, monthly assessed). Conclusions: This pilot study proved the feasibility and acceptance of the app. We will therefore expand its application during biomarker-guided therapies to enable systematic PRO assessments.

Profile of the multicenter cohort of the German Cancer Consortium's Clinical Communication Platform.

Treatment concepts in oncology are becoming increasingly personalized and diverse. Successively, changes in standards of care mandate continuous monitoring of patient pathways and clinical outcomes based on large, representative real-world data. The German Cancer Consortium's (DKTK) Clinical Communication Platform (CCP) provides such opportunity. Connecting fourteen university hospital-based cancer centers, the CCP relies on a federated IT-infrastructure sourcing data from facility-based cancer registry units and biobanks. Federated analyses resulted in a cohort of 600,915 patients, out of which 232,991 were incident since 2013 and for which a comprehensive documentation is available. Next to demographic data (i.e., age at diagnosis: 2.0% 0-20 years, 8.3% 21-40 years, 30.9% 41-60 years, 50.1% 61-80 years, 8.8% 81+ years; and gender: 45.2% female, 54.7% male, 0.1% other) and diagnoses (five most frequent tumor origins: 22,523 prostate, 18,409 breast, 15,575 lung, 13,964 skin/malignant melanoma, 9005 brain), the cohort dataset contains information about therapeutic interventions and response assessments and is connected to 287,883 liquid and tissue biosamples. Focusing on diagnoses and therapy-sequences, showcase analyses of diagnosis-specific sub-cohorts (pancreas, larynx, kidney, thyroid gland) demonstrate the analytical opportunities offered by the cohort's data. Due to its data granularity and size, the cohort is a potential catalyst for translational cancer research. It provides rapid access to comprehensive patient groups and may improve the understanding of the clinical course of various (even rare) malignancies. Therefore, the cohort may serve as a decisions-making tool for clinical trial design and contributes to the evaluation of scientific findings under real-world conditions.

Clinical outcome of biomarker-guided therapies in adult patients with tumors of the nervous system.

Background: The clinical utility of molecular profiling and targeted therapies for neuro-oncology patients outside of clinical trials is not established. We aimed at investigating feasibility and clinical utility of molecular profiling and targeted therapy in adult patients with advanced tumors in the nervous system within a prospective observational study. Methods: molecular tumor board (MTB)@ZPM (NCT03503149) is a prospective observational precision medicine study for patients with advanced tumors. After inclusion of patients, we performed comprehensive molecular profiling, formulated ranked biomarker-guided therapy recommendations based on consensus by the MTB, and collected prospective clinical outcome data. Results: Here, we present initial data of 661 adult patients with tumors of the nervous system enrolled by December 31, 2021. Of these, 408 patients were presented at the MTB. Molecular-instructed therapy recommendations could be made in 380/408 (93.1%) cases and were prioritized by evidence levels. Therapies were initiated in 86/380 (22.6%) cases until data cutoff. We observed a progression-free survival ratio >1.3 in 31.3% of patients. Conclusions: Our study supports the clinical utility of biomarker-guided therapies for neuro-oncology patients and indicates clinical benefit in a subset of patients. Our data might inform future clinical trials, translational studies, and even clinical care.

Next-Generation Sequencing of Advanced GI Tumors Reveals Individual Treatment Options.

PURPOSE: Precision oncology connects highly complex diagnostic procedures with patient histories to identify individualized treatment options in interdisciplinary molecular tumor boards (MTBs). Detailed data on MTB-guided treatments and outcome with a focus on advanced GI cancers have not been reported yet. PATIENTS AND METHODS: Next-generation sequencing of tumor and normal tissue pairs was performed between April 2016 and February 2018. After identification of relevant molecular alterations, available clinical studies or in-label, off-label, or matched experimental treatment options were recommended. Follow-up data and a response assessment that was based on radiologic imaging were recorded. RESULTS: Ninety-six patients were presented to the MTB of Tuebingen University Hospital. Sixteen (17%) showed "pathogenic" or "likely pathogenic" germline variants. Recommendations on the basis of molecular alterations or tumor mutational burden were given for 41 patients (43%). Twenty-five received the suggested drug, and 20 were evaluable for best response assessment. Three patients (15%) reached a partial response (PR), and 6 (30%), stable disease (SD), whereas 11 (55%) had tumor progression (progressive disease). Median progression-free survival (PFS) for all treated and evaluable patients was 2.8 months (range, 1.0-9.0 months), and median overall survival (OS) of all treated patients was 5.2 months (range, 0.1 months to not reached). Patients with SD for ≥ 3 months or PR compared with progressive disease showed both a statistically significant longer median PFS (7.8 months [95% CI, 4.2 to 11.4 months] v 2.2 months [95% CI, 1.5 to 2.8 months], P < .0001) and median OS (18.0 months [95% CI, 10.4 to 25.6 months] v 3.8 months [95% CI, 2.3 to 5.4 months], P < .0001). CONCLUSION: Next-generation sequencing diagnostics of advanced GI cancers identified a substantial number of pathogenic or likely pathogenic germline variants and unique individual treatment options. Patients with PR or SD in the course of MTB-recommended treatments seemed to benefit with respect to PFS and OS.

Does menopausal status impact urinary continence outcomes following abdominal sacrocolpopexy without anti-incontinence procedures in continent women?

OBJECTIVE: We investigated the impact of menopausal status on urinary continence following abdominal sacrocolpopexy (ASC) without an anti-incontinence procedure in continent women. METHODS: We conducted a clinical follow-up study of 137 patients diagnosed with stage 3 or higher pelvic organ prolapse (POP) without urinary incontinence between January 2012 and December 2014. Patients were provided with detailed a priori information pertaining to the abdominal sacrocolpopexy procedure and were invited to attend follow-up visits at 1, 3, 12, and 24 months. Follow-up visits included a gynecological examination, cough test, and validated Urinary Distress Inventory-6 (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7) questionnaires. RESULTS: The mean follow-up time for the cohort was 16.5±3.45 months. The study group was divided according to menopausal status: premenopausal (Group-1) and postmenopausal women (Group-II). Anatomical recurrence was not detected during the follow-up period in either group, but de novo stress urinary incontinence was seen in 15 of 53 (28.3%) Group-I patients and in 6 of 84 (7.1%; p < 0.01) Group-II patients. CONCLUSIONS: The risk of de novo stress urinary incontinence in postmenopausal women after ASC is low. However, premenopausal patients have a higher incidence of de novo stress incontinence which affect quality of life.

The effect of placental removal method on perioperative hemorrhage at cesarean delivery; a randomized clinical trial.

PURPOSE: The aim of this prospective randomized clinical study is to compare whether the removal methods of placenta during cesarean section have an impact on perioperative hemorrhage. METHODS: One hundred women with singleton term pregnancies undergoing elective cesarean section through lower segment transverse incision under general anesthesia were included in this study. They were randomly allocated to two groups according to the type of removal of the placenta from the uterus after childbirth; manually or spontaneously. The main outcome measures were change in hemoglobin levels after cesarean section. The secondary outcomes were operative time, required transfusions and postcesarean endometritis. RESULTS: Fifty patients were randomized to the manual removal group and 50 to the spontaneous group. The demographic characteristics of the two groups were similar. There were no difference in terms of change in hemoglobin levels after cesarean section between two groups (1.6 ± 1.0 and 1.5 ± 1.0, respectively; P = 0.711). In addition, none of the patients required blood transfusion and showed postpartum infections. CONCLUSION: There is not an association between the method of removal of the placenta and postpartum blood loss in cesarean section deliveries.

Is adenomyosis associated with the risk of endometrial cancer?

AIM: To evaluate an association of adenomyosis with endometrial cancer and to determine the frequency of adenomyosis at hysterectomy specimens. METHODS: This study was carried out retrospectively on pathologic specimens of hysterectomies. A total of 472 women in the period 2007-2011 enrolled to the study. All pathologies seen in hysterectomy specimens were noted. The frequency of adenomyosis and the accompanying pathologies were determined. These women were categorized into two groups according to the presence of adenomyosis. The incidence of adenomyosis was analyzed together with the endometrial cancer. RESULTS: The incidence of adenomyosis was 20.8% at hysterectomy specimens. There was no statistically significant difference between the mean age of the two groups (p = 0.069). There were 98 cases with adenomyosis and the only pathologic finding was adenomyosis, in 28 (28.5%) cases. The most common accompanying pathologies with adenomyosis were uterine myomas in 51 (52%), uterine polyps in 16 (16.3%) and endometrial carcinomas in 11 (11.2%) cases. However, statistically significant association of the presence of adenomyosis with uterine myoma (p = 0.227) and endometrial polyps (p = 0.997) and endometrial carcinoma (p = 0.771) was not found. CONCLUSION: In hysterectomy specimens, no statistically significant difference was determined between the groups with and without adenomyosis in terms of co-occurrence with endometrial carcinoma.