Relevant Deterioration Research Articles

1511CIMmH, an mHealth Comprehensive Intervention Model for esophageal cancer patients: A Multi-center RCT Protocol

Abstract Background Post-esophagectomy patients often experience a clinically relevant deterioration of quality of life after esophagectomy due to malnutrition, impaired exercise capacity, and psychological problems. The widespread use of mobile health (mHealth) has been increasingly promising for interdisciplinary healthcare givers to deliver efficient and potential cost-effective interventions in cancer patients. However, comprehensive interventions delivered by mHealth with a rigorous design of randomized controlled trial in post-esophagectomy patients were scarce. Methods This study developed the first comprehensive intervention model by mHealth with a parallel RCT design, providing nutrition, physical exercise, and psychological support for post-esophagectomy patients. A total of 120 patients will be randomized into the intervention group or the control group receiving treatment as usual. Participants in the intervention group will receive the 3-month intervention of the CIMmH program via the enhanced WeChat platform and by specialists (offline). The online program includes nutrition guidelines, physical exercise instructions, and psychological courses. All participants will be assessed at baseline, 1, and 3 months after esophagectomy. The primary outcomes are health-related QOL, weight, and physical fitness measured by 6-minute walking distance. Secondary outcomes include nutritional biomarkers, body composition, strength, interleukin-6, depressive symptoms, anxiety, and coping. Discussion This study is among the first efforts to innovatively develop a comprehensive intervention program to prompt rehabilitation in post-esophagectomy patients. Once proven effective, CIMmH could be integrated into the management of post-esophagectomy patients. Key messages Esophageal cancer, QOL, Nutrition, Physical exercise, Psychological support, mHealth

930Development and feasibility of a mHealth supported Comprehensive Intervention Model (“CIMmH”) for esophageal cancer patients

Abstract Background Esophageal cancer patients often experience a clinically relevant deterioration of quality of life (QoL) after esophagectomy due to malnutrition, lack of physical exercise, and psychological problems. This study aims to evaluate the feasibility and efficacy of a comprehensive intervention model using the mHealth system (CIMmH) on the mobile platform that offers accessible nutritional, exercise, and psychosocial support to esophageal cancer patients after esophagectomy. Methods Twenty esophageal cancer patients were invited to join the CIMmH for 12 weeks. The CIMmH included an online component and an offline consultation component. The participants were assessed before surgery and at 1-month and 3-month intervals after esophagectomy. QoL, depressive symptoms, anxiety, stress, nutrition, and physical fitness were measured. Results Sixteen out of 20 (80%) completed the program. One month after esophagectomy, the global health scale significantly decreased while fatigue, pain, and dyspnea increased. At the 3-month follow-up, only pain, difficulty with eating, dry mouth and trouble with talking were significantly worse than the baseline. All other dimensions in the QoL returned to the preoperative level. Weight and BMI were reduced throughout the study and no significant changes were observed in physical fitness. Depressive symptoms significantly increased one month after surgery. Conclusions The CIMmH had good feasibility and demonstrated encouraging preliminary efficacy for enhancing recovery after surgery among esophageal cancer patients in China. Key messages Esophageal cancer, Quality of life, Nutrition, Physical exercise, Psychological support, Mobile Health (mHealth)

Effectiveness of Internet-Based Cognitive Behavior Therapy (Fatigue in Teenagers on the Internet) for Adolescents With Chronic Fatigue Syndrome in Routine Clinical Care: Observational Study.

BackgroundInternet-based cognitive behavior therapy (I-CBT) for adolescents with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has been shown to be effective in a randomized controlled trial (RCT; Fatigue in Teenagers on the Internet [FITNET]). FITNET can cause a significant reduction in fatigue and disability.ObjectiveWe aimed to investigate whether FITNET treatment implemented in routine clinical care (IMP-FITNET) was as effective, using the outcomes of the FITNET RCT as the benchmark.MethodsOutcomes of CFS/ME adolescents who started IMP-FITNET between October 2012 and March 2018 as part of routine clinical care were compared to the outcomes in the FITNET RCT. The primary outcome was fatigue severity assessed posttreatment. The secondary outcomes were self-reported physical functioning, school attendance, and recovery rates. Clinically relevant deterioration was assessed posttreatment, and for this outcome, a face-to-face CBT trial was used as the benchmark. The attitude of therapists toward the usability of IMP-FITNET was assessed through semistructured interviews. The number of face-to-face consultations during IMP-FITNET was registered.ResultsOf the 384 referred adolescents with CFS/ME, 244 (63.5%) started IMP-FITNET, 84 (21.9%) started face-to-face CBT, and 56 (14.6%) were not eligible for CBT. Posttreatment scores for fatigue severity (mean 26.0, SD 13.8), physical functioning (mean 88.2, SD 15.0), and full school attendance (mean 84.3, SD 26.5) fell within the 95% CIs of the FITNET RCT. Deterioration of fatigue and physical functioning after IMP-FITNET was observed at rates of 1.2% (n=3) and 4.1% (n=10), respectively, which is comparable to a waiting list condition (fatigue: 1.2% vs 5.7%, χ21=3.5, P=.06; physical functioning: 4.1% vs 11.4%, χ21=3.3, P=.07). Moreover, 41 (16.8%) IMP-FITNET patients made use of face-to-face consultations.ConclusionsIMP-FITNET is an effective and safe treatment for adolescents with CFS/ME in routine clinical care.

Health‐related quality of life with fixed‐duration venetoclax‐obinutuzumab for previously untreated chronic lymphocytic leukemia: Results from the randomized, phase 3 CLL14 trial

Chronic lymphocytic leukemia (CLL)-related symptoms impair the well-being of patients, making improvement of health-related quality of life (QoL) a goal of treatment. The CLL14 trial demonstrated higher efficacy of fixed-duration venetoclax-obinutuzumab (Ven-Obi) compared to chlorambucil-obinutuzumab (Clb-Obi) in patients with previously untreated CLL. To assess patients' QoL, the following patient-reported outcomes (PRO) measures were assessed: the M.D. Anderson Symptom Inventory (MDASI) core instrument and CLL module and the EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). At treatment start, physical functioning (mean 75.9 [standard deviation (SD) ± 20.1] in the Clb-Obi arm and 76.9 [±19.4] in the Ven-Obi arm), role functioning (73.6 [±27.86] and 72.6 [±26.9]) and GHS/QoL (63.6 [±21.0] and 60.3 [±20.5]) were comparable between treatment arms per EORTC QLQ-C30 scale scores. Baseline levels of physical and role functioning were maintained throughout treatment and follow-up, with no relevant improvement or deterioration. On average, patients treated with Ven-Obi showed a meaningful improvement of GHS/QoL during treatment and follow-up by at least eight points at cycle three, whereas improvement was delayed until cycle eight with Clb-Obi. According to MDASI scores, CLL symptoms (1.5 [±1.2] and 1.6 [±1.3]), core cancer symptoms (1.5 [±1.4] and 1.8 [±1.7]) and symptom interference (2.1 [±2.3] and 2.3 [±2.3]) were generally low and comparable between treatment arms at baseline and were maintained throughout treatment and follow-up. This analysis demonstrates that the higher efficacy of Ven-Obi is not associated with QoL impairment and that Ven-Obi achieves early relief of CLL-related symptoms in elderly unfit patients.

Health-related quality of life (QoL) in platinum-resistant ovarian cancer patients treated with olaparib and pegylated liposomal doxorubicin (PLD), a multicenter single-arm phase II clinical trial (ROLANDO, GEICO-1601).

5549 Background: The prognosis for patients with platinum-resistant/refractory ovarian cancer (PROC) is poor, and the aim of treatment is focused primarily on symptom control and maintenance of QoL. The objective of this study was to assess the impact on QoL of the combination of pegylated liposomal doxorubicin (PLD) with olaparib (OLA) in PROC patients (pts). Methods: ROLANDO is a single arm phase II trial that enrolled pts with high-grade serous or endometrioid and at least one previous PROC recurrence (between 28 days - 6 months after last platinum). Up to 4 previous lines (up to 5 in BRCA-mut) were allowed. Pts received 6 cycles of PLD 40 mg/m2 intravenously every 28 days + OLA 300 mg b.i.d. followed by OLA 300 mg b.i.d. monotherapy until progression or unacceptable toxicity. QoL was measured by European Organization for Research and Treatment of Cancer QLQ C30 questionnaire evaluating functional status, and symptom intensity and QLQ OV-28 ovarian cancer specific module, both filled out by pts every 4 months (mo) regardless of disease progression. Questionnaire compliance was reported as percentage of the initial number of pts. Changes between baseline and subsequent visits (Wilcoxon rank test) were evaluated. P values < 0.05 were considered significant. Results: From 2017 to 2020, 31 pts were recruited. Median age was 57 y.o., ECOG 0/1: 32.3%/67.7%. Median of prior lines was 2 (range 1-5) and pts were on study treatment for a median of 5 mo (range 1.4-19.5) for OLA and 5 cycles (range 2 - 6) for PLD. QoL information was available at baseline for 30 (97%) pts and decayed to 22 (71%), 13 (42%), 6 (19%) and 4 (13%) pts at 4, 8, 12, and 16 mo respectively. Global health status measured by QLQ C30 and QLQ OV-28 scores was maintained throughout all time points with no significant differences. Significant transient improvement was seen in social functioning after 12 mo (p = 0.013). Nausea-vomiting (p = 0.02), hair loss (p = 0.012) and constipation (p = 0.037) showed a significant increase at 4 mo overlapping with PLD administration, and returned to baseline levels afterwards. This was in line with the reported adverse reactions frequency of nausea (58.1%) and vomiting (45.2%). Dyspnea showed a transient significant increase at 12 mo (p = 0.012), whereas insomnia (p = 0.038) and attitude towards disease (p = 0.007) improved at 16 mo. Symptoms such as appetite and constipation did not change after 12 mo. Most functional scales (physical, role, emotional, cognitive, body, sexuality) and symptom scales (fatigue, pain, appetite loss, diarrhoea, neurologic, hormonal and economic burden) had no statistically significant changes. Conclusions: Pts treated with OLA+PLD combination reported no signs of clinically relevant deterioration of QoL while on treatment. All QoL items changes were transient in no more than 1 time-point. Clinical trial information: NCT03161132.

Heterotopic Ossification Following Arthroplasty for Femoral Neck Fracture.

Heterotopic ossification (HO) is a frequent complication following hip surgery. Using data from the Hip Fracture Evaluation with Alternatives of Total Hip Arthroplasty versus Hemiarthroplasty (HEALTH) trial, we aimed to (1) determine the prevalence of HO following total hip arthroplasty (THA) for femoral neck fracture in patients ≥50 years of age, (2) identify whether HO is associated with an increased risk of revision surgery within 24 months after the fracture, and (3) determine the impact of HO on functional outcomes. We performed a multivariable Cox regression analysis using revision surgery as the dependent variable and HO as the independent variable. We compared Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores between participants with and those without HO at 24 months. Of 1,441 participants in the study, 287 (19.9%) developed HO within 24 months. HO was not associated with subsequent revision surgery. Grade-III HO was associated with statistically significant and clinically relevant deterioration in the total WOMAC score, which was mainly related to the function component of the score, compared with grade I or II. The impact of grade-III HO on the functional outcomes and quality of life after THA for hip fracture is clinically important, and HO prophylaxis for selected high-risk patients may be appropriate. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial

The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial. HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c-T3a with one or two of the following risk factors: stage T3a; Gleason score ≥7; and prostate-specific antigen 10-20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0-2. Participants were randomly assigned (1:1) to conventional fractionation (78·0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the per-protocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321. Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25-72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency [p<0·0001], rush to toilet [p=0·0013], flatulence [p=0·0013], bowel cramp [p<0·0001], mucus [p=0·0014], blood in stool [p<0·0001], and limitation in daily activity [p=0·0014]). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year follow-up there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 [33%] of 132 for conventional fractionation vs 33 [28%] of 120 for ultra-hypofractionation; mean difference 5·1% [95% CI -4·4 to 14·6]; p=0·38), overall bowel bother (43 [33%] of 129 vs 34 [28%] of 123; 5·7% [-3·8 to 15·2]; p=0·33), overall sexual bother (75 [60%] of 126 vs 59 [50%] of 117; 9·1% [-1·4 to 19·6]; p=0·15), or global health/QOL (56 [42%] of 134 vs 46 [37%] of 125; 5·0% [-5·0 to 15·0]; p=0·41). Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer. The Nordic Cancer Union, the Swedish Cancer Society, and the Swedish Research Council.

The Schulthess local Shoulder Arthroplasty Registry (SAR): cohort profile

PurposeClinical registries are essential for evaluation of surgical outcomes. The Schulthess Shoulder Arthroplasty Registry (SAR) was established in 2006 to evaluate safety, function, quality-of-life and patient satisfaction in patients undergoing...

Health-related quality of life after ultrafocal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer: reporting the patient’s perspective

PurposeFor patients with a localized prostate cancer recurrence after radiotherapy, focal salvage treatment offers a less toxic alternative to whole-gland treatments, with the potential of preserving health-related quality of life (HR-QoL). With a focus on the patient’s perspective of treatment, this study aims to describe HR-QoL after ultrafocal salvage high-dose-rate brachytherapy (HDR-BT), and to explore predictive factors affecting HR-QoL. Material and methodsWe included 100 patients treated with ultrafocal salvage HDR-BT. Prostate cancer-related HR-QoL was assessed by the EORTC QLQ-PR25 questionnaire. Domains were urinary symptoms, bowel symptoms and sexual activity/functioning. For each domain, a mixed effects model was made to estimate HR-QoL trends over time. For domains showing clinically relevant change (≥10 points difference), the mixed effects model was used to explore potential predictors (age, baseline HR-QoL score, T-stage, tumor location, CTV size, dose to organs at risk and history of ADT). ResultsMedian follow-up was 20 months (IQR 13–30). Mean questionnaire response rate was 86% (range 72–100%). Median baseline scores were 12 (urinary), 0 (bowel) and 67/50 (sexual activity/functioning). Urinary symptoms and sexual functioning showed clinically relevant deterioration over time (maximum difference of 11 and 12 points, respectively). Worse baseline score and higher administered dose to the urethra (≥16 Gy) were predictive of increased urinary symptoms (p < 0.01 and p = 0.03). Better baseline score was predictive of better sexual functioning (p < 0.01). ConclusionUltrafocal salvage HDR-BT has negligible impact on bowel symptoms but does affect urinary symptoms and sexual functioning. Lower impact is predicted for patients with favorable urinary and sexual function at baseline. Urethral dose constraints should be closely monitored.

Determinants of health-related quality of life decline in interstitial lung disease

BackgroundHealth-related quality of life (HRQL) in interstitial lung disease (ILD) patients is impaired. We aimed to identify baseline predictors for HRQL decline within a 12-month observation period.MethodsWe analyzed 194 ILD patients from two German ILD-centers in the observational HILDA study. We employed the disease-specific King’s Brief Interstitial Lung Disease questionnaire (K-BILD) with the subdomains ‘psychological impact’, ‘chest symptoms’ and ‘breathlessness and activities’, and the generic EQ-5D Visual Analog Scale (VAS). We evaluated how many patients experienced a clinically meaningful decline in HRQL. Subsequently, we investigated medical and sociodemographic factors as potential predictors of HRQL deterioration.ResultsWithin the study population (34.0% male, Ø age 61.7) mean HRQL scores hardly changed between baseline and follow up (K-BILD: 52.8 vs. 52.5 | VAS: 60.0 vs. 57.3). On the intra-individual level, 30.4% (n = 59) experienced a clinically relevant deterioration in K-BILD total score and 35.4% (n = 68) in VAS. Lower baseline forced vital capacity (FVC) % predicted determined HRQL decline in K-BILD total score (ß-coefficient: − 0.02, p = 0.007), VAS (ß-coefficient: − 0.03, p < 0.0001), and in the subdomain ‘psychological impact’ (ß-coefficient: − 0.02, p = 0.014). Lower baseline diffusing capacity of carbon monoxide (DLCO) % predicted determined deterioration in ‘breathlessness and activities’ (ß-coefficient: − 0.04, p = 0.003) and ‘chest symptoms’ (ß-coefficient: − 0.04, p = 0.002). Additionally, increasing age predicted decline in ‘psychological impact’ (ß-coefficient: 0.06, p < 0.007).ConclusionAround a third of ILD patients experienced a clinically relevant HRQL deterioration in a 12-month period, which was associated with baseline lung function values in all K-BILD domains. As lung function values are time-dependent variables with possible improvements, in contrast to age and ILD subtype, it, thus, seems important to improve lung function and prevent its decline in order to maintain HRQL on the possibly highest level.

Development and Feasibility of a Mobile Health-Supported Comprehensive Intervention Model (CIMmH) for Improving the Quality of Life of Patients With Esophageal Cancer After Esophagectomy: Prospective, Single-Arm, Nonrandomized Pilot Study.

BackgroundPatients with esophageal cancer often experience clinically relevant deterioration of quality of life (QOL) after esophagectomy owing to malnutrition, lack of physical exercise, and psychological symptoms.ObjectiveThis study aimed to evaluate the feasibility, safety, and efficacy of a comprehensive intervention model using a mobile health system (CIMmH) in patients with esophageal cancer after esophagectomy.MethodsTwenty patients with esophageal cancer undergoing the modified McKeown surgical procedure were invited to join the CIMmH program with both online and offline components for 12 weeks. The participants were assessed before surgery and again at 1 and 3 months after esophagectomy. QOL, depressive symptoms, anxiety, stress, nutrition, and physical fitness were measured.ResultsOf the 20 patients, 16 (80%) completed the program. One month after esophagectomy, patients showed significant deterioration in overall QOL (P=.02), eating (P=.005), reflux (P=.04), and trouble with talking (P<.001). At the 3-month follow-up, except for pain (P=.02), difficulty with eating (P=.03), dry mouth (P=.04), and trouble with talking (P=.003), all other QOL dimensions returned to the preoperative level. There were significant reductions in weight (P<.001) and BMI (P=.02) throughout the study, and no significant changes were observed for physical fitness measured by change in the 6-minute walk distance between baseline and the 1-month follow-up (P=.22) or between baseline and the 3-month follow-up (P=.52). Depressive symptoms significantly increased 1 month after surgery (P<.001), while other psychological measures did not show relevant changes. Although there were declines in many measures 1 month after surgery, these were much improved at the 3-month follow-up, and the recovery was more profound and faster than with traditional rehabilitation programs.ConclusionsThe CIMmH was feasible and safe and demonstrated encouraging efficacy testing with a control group for enhancing recovery after surgery among patients with esophageal cancer in China.Trial RegistrationChinese Clinical Trial Registry (ChiCTR-IPR-1800019900); http://www.chictr.org.cn/showprojen.aspx?proj=32811.

Multi-Temporal UAV Data and Object-Based Image Analysis (OBIA) for Estimation of Substrate Changes in a Post-Bleaching Scenario on a Maldivian Reef

Coral reefs are declining worldwide as a result of the effects of multiple natural and anthropogenic stressors, including regional-scale temperature-induced coral bleaching. Such events have caused significant coral mortality, leading to an evident structural collapse of reefs and shifts in associated benthic communities. In this scenario, reasonable mapping techniques and best practices are critical to improving data collection to describe spatial and temporal patterns of coral reefs after a significant bleaching impact. Our study employed the potential of a consumer-grade drone, coupled with structure from motion and object-based image analysis to investigate for the first time a tool to monitor changes in substrate composition and the associated deterioration in reef environments in a Maldivian shallow-water coral reef. Three key substrate types (hard coral, coral rubble and sand) were detected with high accuracy on high-resolution orthomosaics collected from four sub-areas. Multi-temporal acquisition of UAV data allowed us to compare the classified maps over time (February 2017, November 2018) and obtain evidence of the relevant deterioration in structural complexity of flat reef environments that occurred after the 2016 mass bleaching event. We believe that our proposed methodology offers a cost-effective procedure that is well suited to generate maps for the long-term monitoring of changes in substrate type and reef complexity in shallow water.

Role of RDW in mathematical formulas aiding the differential diagnosis of microcytic anemia

Many mathematical formulas containing simple red blood cell parameters have been proposed for differentiating between iron deficiency and thalassemia in patients with microcytic anemia. Approximately half of these formulas do include red cell distribution width (RDW), along with other red cell parameters. In the present study we investigated the role of RDW, expressed in relative or in absolute units in relation with the formulas’ discriminant performance. We used a database containing over 2200 subjects with microcytic anemia, for whom a final diagnosis (iron-deficiency anemia, thalassemia, both or other) was available. Performance of the discriminant formulas was assessed by Receiver Operator Curve analysis. Substitution of relative by absolute RDW resulted in statistically significant performance increase (area under the ROC curve) in 16 out of 23 formulas, predominantly due to increased specificity. Relevant performance deterioration was seen in only three formulas that had low initial performance already with the original relative RDW. For optimal differential diagnostic performance, an RDW-based formula for distinguishing thalassemia from iron-deficiency anemia in microcytic anemia should contain ‘absolute’ instead of relative RDW.

Endoscopic vacuum therapy for treatment of rectal stump leakage.

Symptomatic rectal stump leakage (RSL) is a serious complication after discontinuity resection and requires immediate surgical, interventional, or endoscopic therapy. Re-operations are associated with high morbidity and mortality in these mostly very ill patients. Endoscopic vacuum therapy (EVT) has been established for management of anastomotic leakage; however, its effectiveness for RSL treatment has not been analyzed in detail yet. A retrospective analysis of patients treated with EVT for RSL between 2001 and 2018 analyzing factors predicting therapy success and duration was carried out. Fifty-six patients with RSL at a median age of 66years were included. Of these, 18 patients (32%) had been referred for EVT from external departments or institutions. RSL was associated with a relevant clinical deterioration in all patients, and 55 patients (98%) had been classified as ASA 3 and 4, preoperatively. In 9 patients (16%), additional surgical revision was necessary with initiation of EVT. In 47 patients (84%), EVT was successful and local control of the inflammatory focus was achieved. The median duration of therapy was 20days. Two patients (4%) suffered from minor EVT-associated bleeding that was endoscopically controlled. Preoperative radiation of the pelvis was significantly associated with EVT failure (P = 0.035), whereas patient age represented a predictive factor for therapy length (P = 0.039). In 12 patients (21%), restoration of intestinal continuity was achieved in the further course. We present the first specific series on EVT for RSL. EVT for RSL was shown to be an effective and safe minimal-invasive treatment option, avoiding surgical revision in the majority of patients.

Acute patient-reported toxicities after proton therapy or intensity-modulated radiotherapy for prostate cancer.

305 Background: Toxicity due to radiotherapy (RT) may differ in patients (pts) with prostate cancer who receive intensity-modulated radiotherapy (IMRT) or proton beam therapy (PBT). Methods: Patient-reported bowel function (BF), urinary incontinence (UI), and urinary irritative/obstructive symptoms (UO) domains of the Expanded Prostate Index Composite Questionnaire (EPIC-26) were prospectively collected in pts with localized prostate cancer receiving either IMRT (n=157) or PBT (n=105) to the prostate +/- proximal seminal vesicles for clinical stage T1-T2 N0 prostate cancer at a single tertiary cancer center between 2015 and 2018. Changes in domain scores were analyzed from pretreatment to the end of RT and 3 months post-RT, assessing the acute effects of each modality. A clinically relevant change was defined as a score change that exceeded 50% of the standard deviation of a baseline value. Results: At baseline there was no difference in the scores of BF, UI, and UO domains between IMRT and PBT cohorts. At the end of RT, pts treated with either modality had a statistically significant and clinically relevant worsening of BF and UO compared to baseline. Pts treated with IMRT experienced a significantly greater decrement in BF compared to the PBT cohort (-13 vs -9, p&lt;0.01), including significantly more IMRT pts having a clinically relevant deterioration in BF compared to PBT pts (58% vs 40%, p=0.01). Though there was a statistically significant deterioration in UI in the IMRT cohort (-4, p&lt;0.001), this did not reach the predefined threshold for clinical relevance. Three months following RT, the IMRT group continued to have statistically significant and clinically relevant worsening of BF (-9, p&lt;0.001), whereas the change in BF domain score of the PBT cohort was no longer statistically significant or clinically relevant compared to baseline (-1, p=0.25). There were no statistically significant or clinically relevant changes in UO or UI in either cohort at three months when compared to baseline. Conclusions: Pts who received IMRT or PBT reported unique patterns of toxicity, and pts treated with IMRT had worse decrement in BF immediately after and three months following RT, compared to those treated with PBT.

Effects of one-lung flooding on porcine haemodynamics and gas exchange.

Background and aim: We established a porcine model of one-lung flooding (OLF) that can be used for research on the use of ultrasound for lung tumour detection, ultrasound-guided transthoracic needle biopsy, and tumour ablation. However, OLF requires one-lung ventilation (OLV) and eliminates the recruitment strategies of the nonventilated lung. During thoracic surgery, OLV alone can be associated with hypoxia, hypercapnia, and right ventricular overload. Here, we examined whether OLF influences haemodynamics and gas exchange indices during and after OLV/OLF compared with OLV/apnoea and two-lung ventilation (TLV) following deflooding.Methods: Fourteen pigs were included in this study: five were allocated to the control group (CO) and nine were assigned to the OLF group (OLF). Assessments of haemodynamics, gas exchange, and lung sonography were performed after baseline measurements, during OLV/apnoea, OLV/OLF, and after deflooding and TLV. The volume of extravascular lung water was also measured.Results: OLF induced no significant deterioration of oxygenation or ventilation during OLF or after deflooding and TLV. Color-coded duplex sonography of the pulmonary artery in the flooded lung demonstrated an oscillating flow that corresponded to intrapulmonary circulatory arrest. After flooding of the nonventilated lung, the partial pressure of O2 in the arterial blood increased and the shunt fraction decreased significantly compared to OLV/apnoea conditions. After deflooding and TLV, haemodynamics and gas exchange indices showed no differences compared to the CO group and baseline values, respectively.Conclusions: OLF is safe to use during acute animal experimentation. No clinically relevant deterioration of haemodynamics or gas exchange occurred during or after OLF. Due to the circulatory arrest in the flooded lung, the right-to-left shunt volume in the nonventilated lung was minimized. Survival experiments are necessary to further assess the utility of this method.

Transarterial chemoembolization for hepatocellular carcinoma: quality of life, tumour response, safety and survival comparing two types of drug-eluting beads.

To compare two different types of drug-eluting microspheres with regard to impact on HRQoL after first TACE, tumour response, peri-procedural complications, adverse events and 1-year survival in patients suffering from unresectable hepatocellular carcinoma (HCC). HRQoL was prospectively assessed with validated questionnaires (EORTC QLQ-C30 and -HCC18) before and 2weeks after treatment with their first drug-eluting beads (DEB-)TACE with either acrylamido-polyvinylalcohol-AMPS hydrogel microspheres (groupDCB; 20 patients) or polyvinyl alcohol-co-acrylic acid microspheres (groupHS; 16 patients). Baseline characteristics, peri-procedural complications, treatment-related adverse events and 1-year survival were compared between both types of microspheres. Treatment response and objective response rates (ORR) were analysed using established tumour response criteria. Subgroup analysis for pooled groups with small (groupSMALL; 21 patients) versus large particles (groupLARGE; 15 patients) was performed. At baseline, there were no significant differences between the treated microsphere groups. No significant differences were found in absolute HRQoL changes after first DEB-TACE between the different types of microspheres. Response rates and survival were comparable between the investigated microsphere groups. For groupSMALL, we found a significant difference in post-interventional deterioration of physical function (- 19.4%) compared to groupLARGE (- 8%; p = 0.025). Tumour response and ORR according to mRECIST were significantly higher in groupSMALL (p = 0.008; p = 0.009). DEB-TACE is generally well tolerated and effective, with comparable changes in HRQoL for both types of drug-eluting microspheres. Tumour response is better with small microspheres. A relevant deterioration of physical function underlines that an aggressive TACE using small beads should be well deliberated.

Rapid Improvement of Patient-Reported Outcomes with Venetoclax Plus Obinutuzumab in Patients with Previously Untreated CLL and Coexisting Conditions: A Prospective Analysis from the CLL14 Trial

Rapid Improvement of Patient-Reported Outcomes with Venetoclax Plus Obinutuzumab in Patients with Previously Untreated CLL and Coexisting Conditions: A Prospective Analysis from the CLL14 Trial

QOLP-04. CALCULATING THE NET CLINICAL BENEFIT IN BRAIN TUMOR TRIALS BY COMBINING SURVIVAL AND HEALTH-RELATED QUALITY OF LIFE DATA USING TWO METHODS: QUALITY ADJUSTED SURVIVAL EFFECT SIZES AND JOINT MODELLING

Abstract INTRODUCTION The impact of treatment on both the quality and the quantity of life, i.e. the ‘net clinical benefit’, should be considered to facilitate shared decision making. Two methods that combine survival and health-related quality of life (HRQoL) data: Quality Adjusted Effect Sizes (QASES) and Joint Modelling (JM) were applied to gain insight in the net clinical benefit. METHODS The net clinical benefit in one RCT (EORTC 26951 comparing radiotherapy (RT) + PCV chemotherapy versus RT alone) was calculated as a proof of concept for other trials. With the QASES method, effect sizes for differences in survival and HRQoL between treatment arms were calculated. JM allows simultaneous modeling of a longitudinal outcome (HRQoL), and a time-to event outcome (survival). HRQoL scales/items that were selected for primary analysis in the main study were also selected for this analysis: fatigue, global health, social functioning, communication deficit, seizures, physical functioning, and nausea/vomiting. RESULTS 288/386 patients completed baseline HRQoL forms and were included in the analysis. Overall survival (OS) was significantly longer with combined treatment (42.3 vs. 30.6 months). The percentage of patients who experienced a clinically relevant deterioration (≥10 points) in nausea/vomiting, fatigue, social functioning and global health up to one year after treatment compared to baseline was larger in the RT+PCV arm. QASES corresponded to a reduction in the median OS difference from 9.7 months up till 5.5 months, given equal weights to OS and HRQoL. JM analyses resulted in a theoretical loss of treatment effect in OS of 2–6% when adjusting for HRQoL. CONCLUSION Both methods showed that adjusting for the impact of treatment on a relevant HRQoL parameter reduced the survival benefit in the experimental treatment arm compared to standard treatment arm. Applying these methods may facilitate communicating the impact of treatment to patients in clinical practice.

1320P - Health-related quality of life in patients with metastatic Merkel cell carcinoma receiving second-line or later avelumab treatment: 36-month follow-up data

BackgroundIn the single-arm, open-label, multicentre, international phase II trial (NCT02155647 Part A), metastatic Merkel cell carcinoma (mMCC) patients received second-line or later avelumab 10mg/kg every two weeks. Health-related quality of life (HRQoL) was assessed using the skin cancer-specific FACT-M and the generic EQ-5D. We report HRQoL results 36 months after enrolment of the last patient with focus on HRQoL deterioration-free survival (QFS) rates. MethodsHRQoL data were obtained at baseline, week 7, and every 6 weeks until disease progression and/or treatment discontinuation. QFS was defined as the time interval between first dose and HRQoL deterioration event i.e. when a HRQoL domain score (FACT-M/EQ VAS) decreased from baseline equivalent to the minimal important difference (MID) threshold, with no further improvement thereafter. For sensitivity analyses, two thresholds are applied termed as minimum and maximum MID. QFS rates were derived from Kaplan-Meier curves and could be interpreted as the likelihood of a patient to endure a time period without relevant HRQoL deterioration until a certain time point. ResultsBased on the intention-to-treat population (n=88), QFS rates ranged from 40.6% (FACT-M functional well-being, FWB) to 56.3% (EQ VAS) at 12 months when applying minimum MIDs (Table). At 36 months, rates ranged from 20.7% (FWB) to 37.7% (FACT-M social well-being). When applying the maximum MID, QFS rates ranged from 48.6% to 64.9% at 12 months, and 25.3% to 42.7% at 36 months. ConclusionsAs expected, QFS rates decreased over time; however, in the context of an aggressive cancer such as mMCC, various HRQoL domains show promising QFS rates suggesting a substantial proportion of patients reported stable or improved HRQoL on treatment with avelumab across time points, aligned with the clinical efficacy results throughout the long study follow-up of over 36 months.Table1320P HRQoL deterioration-free survival rates (QFS) by time interval (12, 24, 36 months) based on EQ VAS and FACT-M scores applying (negative) minimum/maximum Minimal Important Difference (MID) thresholds, ITT population (N=88)TableMID thresholds1 (min./max.)HRQoL deterioration-free survival rates (%)Minimum MIDMaximum MIDMonth 12Month 24Month 36Month 12Month 24Month 36EQ-5DEQ VAS-7 / -1056.347.434.859.045.538.5FACT-MPhysical well-being (PWB)-1 / -346.743.036.452.646.135.8Social/Family well-being (SWB)-1/ -344.037.737.749.549.540.5Emotional well-being (EWB)-1 / -349.241.032.855.951.242.7Functional well-being (FWB)-2 / -440.632.620.752.848.533.6Melanoma subscale (MS)-2 / -549.745.737.464.949.138.2Melanoma surgery scale (MSS)-2 / -351.451.436.748.648.634.7Trial Outcome Index (TOI)-4 / -950.438.231.261.242.132.7FACT-G Total Score-4 / -846.837.724.051.743.427.6FACT-M Total Score-5 / -1246.637.623.956.939.725.31Published in Bharmal, et al. (2017). "Psychometric properties of the FACT-M questionnaire in patients with Merkel cell carcinoma." Health Qual Life Outcomes 15(1): 247. Legend: HRQoL=Health-Related Quality of Life; QFS=HRQoL deterioration-free survival rate; MID=Minimal Important Difference; ITT=Intention-to-treat population; VAS=visual analogue scale; EQ VAS=VAS of the EQ-5D questionnaire Clinical trial identificationNCT02155647. Legal entity responsible for the studyMerck Healthcare KGaA. FundingThis study was sponsored by Merck Healthcare KGaA, Darmstadt, Germany, and is part of an alliance between Merck Healthcare KGaA, Darmstadt, Germany and Pfizer Inc., New York, NY, USA. DisclosureS.P. D’Angelo: Advisory / Consultancy: Incyte; Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar; Advisory / Consultancy: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: EMD Serono; Advisory / Consultancy: GSK; Advisory / Consultancy: ImmuneDesign; Travel / Accommodation / Expenses: Adaptimmune. S. Nolte: Full / Part-time employment, Employee of ICON plc, which is a paid consultant to the study sponsor: ICON plc. M. Schlichting: Full / Part-time employment: Merck Healthcare KGaA. M. Henry-Szatkowski: Full / Part-time employment, Employee of ICON plc, which is a paid consultant to the study sponsor: ICON plc. M. Hennessy: Full / Part-time employment: EMD Serono, Inc. M. Bharmal: Full / Part-time employment: Merck Healthcare KGaA.