Adolescents and young adults (AYAs) benefit from healthcare transition (HCT) programs. Despite the well-established literature reviewing HCT, a considerable heterogeneity exists on the involved healthcare professionals. This review aims to explore systematic reviews on the practices and recommendations on which disciplines of professionals should be involved in HCT. An umbrella review was performed using the MEDLINE, EMBASE, and Web of Science databases. To be eligible, systematic reviews had to report on the composition and/or the rationale of members of a transition team. Seventeen reviews were included in this systematic review. A healthcare professional that coordinates HCT was identified as a key caregiver in all reviews. Other reported members of a HCT team were nurses (75

Upper left panel: Image representing a protein array of 507 proteins used for detection of soluble factors present in a mixture of CMCAAT from two patients. Each protein is spotted in duplicate. The boxes show the positive controls. The brackets indicate adiponectin (1) confirming the adipose nature of CMCAAT, GCSF (2), IL-6 (3), IL-8 (4), leptin (5), LIF (6), OSM (7). Upper right panels: western blot analysis of Y705 pSTAT3 of MCF-7 cells treated for 48h with control medium; neutralizing antibodies against hIL-6, hLIF and hIL-8 (1 µg/ml); rhIL-6, rhLIF and rhIL-8 (10 ng/ml); combination of the recombinant protein with the neutralizing antibody (same concentrations); western blot analysis of MCF-7 cells treated for 48h with CMCAAT and neutralizing antibodies against hIL-6, hLIF and hIL-8 at indicated concentrations. Lower panel: Phase-contrast images of MCF-7 cells treated or 48h with control medium, rhIL-6, rhLIF and rhIL-8 at indicated concentrations, CMCAAT and CMCAAT combined with neutralizing antibodies against hIL-6, hLIF and hIL-8 at indicated concentrations (Scale bar is 100 µm).

<p>F: forward primer, R: reverse primer.</p>

Graphs representing relative mRNA levels of OSMR, LIFR, GP130 and STAT3 in MCF-7 and SKBR3 cells treated for 48h with control medium or rhOSM (2 ng/ml).

Upper panels: Western blot analysis of E-cadherin, beta-catenin, vimentin, fibronectin, pancytokeratin and estrogen receptor alpha (ERα). Left panel: MCF-7 cells treated for 48h with control medium or CMCAAT. Right panel: MCF-7 cells stably transfected with GFP or OSM cDNA, or treated for 48h with rhOSM (1ng/ml). Tubulin serves as an internal control. Lower left panel: Confocal images of the F-actin cytoskeleton (red), nuclear staining DAPI (blue) and merged signals in MCF-7 cells treated for 48h with control medium or CMCAAT (scale bar is 20 μm) and confocal images of E-cadherin (green), beta-catenin (red) and merge signals with DAPI in MCF-7 cells treated for 48h with control medium or CMCAAT (scale bar is 10 μm). Lower right panel: Immunohistochemical staining of MCF-7-GFP and MCF-7-OSM tumor xenografts for E-cadherin, vimentin, pancytokeratin and ERα (scale bar is 25 µm).

<p>Western blot analysis of Y705 and S727 pSTAT3, STAT3, (p)Akt, pS6K, (p)Erk1/2 in MCF-7 cells treated for 48h with rhOSM (1ng/ml) and an Akt-inhibitor or Mek-inhibitor at the indicated concentrations.</p>

Left panel: Graph representing proliferation rate of MCF-7-GFP and MCF-7-OSM cells in time (asterix indicates P = .068). Right upper panel: images of MCF-7-GFP and MCF-7-OSM aggregates embedded in type I collagen (scale bar is 100 µm). Right lower panel: Graph representing relative mRNA levels of OSMR, LIFR, GP130 and STAT3 in MCF-7-GFP and MCF-7-OSM cells.

<p>Supplemental materials and methods in addition to those mentioned in the manuscript.</p>

<p>Flow chart indicating CM^CAAT prepared from 25 breast cancer patients and tested in the experimental conditions described throughout the article. OSM concentration was measured by ELISA for the samples indicated in bold type (see also figure 3C).</p>

<p>Flow chart indicating CM^CAAT prepared from 25 breast cancer patients and tested in the experimental conditions described throughout the article. OSM concentration was measured by ELISA for the samples indicated in bold type (see also figure 3C).</p>

<p>Western blot analysis of Y705 and S727 pSTAT3, STAT3, (p)Akt, pS6K, (p)Erk1/2 in MCF-7 cells treated for 48h with rhOSM (1ng/ml) and an Akt-inhibitor or Mek-inhibitor at the indicated concentrations.</p>

Abstract BackgroundEverolimus in combination with exemestane is indicated for the treatment of hormone receptor-positive, HER 2-neg endocrine resistant advanced breast cancer in postmenopausal women. This study investigated treatment adherence, tolerability, satisfaction and efficacy. MethodsA prospective, non-interventional, non-controlled, multicentric observational study assessed adherence by means of a validated questionnaire (‘Morisky Medication Adherence Scale’) and ‘Medication Event Monitoring System’ (MEMS®) data. The level of adherence was calculated per patient as percentage of days on which the medicine was taken as prescribed during the total treatment period, referred to as ‘unadjusted adherence rate’ (UAR). Second, MEMS® data were adjusted for treatment interruptions according to the CRF and questionnaire data, approved by the treating physician (‘adjusted adherence rate’ (AAR)). Successful adherence was defined as ≥ 95% – ≤ 105%. Validated questionnaires (‘Patient Satisfaction with Cancer Treatment Education’, ‘Cancer Treatment Satisfaction Questionnaire’ (CTSQ) and ‘Functional Assessment of Cancer Therapy – General’ (FACT-G) were used to report patients experience and satisfaction with the treatment and perceived care, questioned at initial visit and after approximately 1, 3, 6 and 12 months. The efficacy was primary analyzed through progression free survival (PFS). ResultsBetween Dec 2015 and Nov 2017, a total of 58 women (median age 65 yrs) from 7 oncology centers were included after a mean of 34m ± 36.9 (SD) of being diagnosed with stage IV disease; most (62.1%) had ≥3 organs involved and 84.5% had ≥2 prior metastatic treatment lines. The mean follow-up duration was 185.5 ± 100.0 days. The mean UAR for exemestane, everolimus and the combination were 92.9 %, 84.8 % and 81.7 % respectively. For everolimus and the combination therapy these rates differ significantly from the mean AAR, with p < 0.05 (see table 1). For the AAR of the combination therapy, 13.8 % of the patients showed optimal adherence (100 %). Six patients (10.3%) interrupted their treatment with exemestane with a mean time of treatment pause of 34.3 ± 19.1 days. The treatment with everolimus was interrupted by 36 (62.1%), with a mean interruption time of 24.3 ± 16.5 days, which corresponds with a mean of 19.6 % ± 17.6% of the total follow-up duration. Some patients interrupted their treatment multiple times. The most common side effect was mucositis (n=26 at 1 month, of whom 8 patients grade 3 and 15 patients grade 2)). Six (10.4 %) of the 58 patients stopped treatment with everolimus and exemestane due to side effects. The median PFS was 170 days. With regard to quality of life, patients scored lowest on emotional and functional well-being. However, there were no significant differences measured for the mean FACT-G score between Day0, M1 and M3 (P = 0.273). Also, patients scored overall low on the ‘CTSQ’. Conclusion Despite close monitoring and preventive measures to overcome side effects, adherence to everolimus and exemestane was rather low. Many patients needed to interrupt the treatment due to side effects; treatment is perceived as intensive. Nevertheless, median PFS is 170 days, even when used late in the therapeutic journey of breast cancer patients. Table 1. UAR and AAR for Exemestane, Everolimus and the combinationExemestaneEverolimusCombination therapyUAR (%)mean ± SD92.97 ± 13.1784.86 ± 19.4081.74 ± 20.98AAR (%)mean ± SD93.07 ± 13.1491.81 ± 15.0487.55 ± 18.17Significance differenceP-value0.277< 0.001< 0.001 Citation Format: Veerle Foulon, Carrie Visser, Sandra De Coster, Lise-Marie Kinnaer, Ellen Reynders, Anne Deblander, Patrick Berteloot, Kevin Punie, Hans Wildiers, Véronique Cocquyt, Hannelore Denys, Ahmad Awada, Eric Strobbe, Andrea Gombos, Isabelle Spoormans, Ximena Elzo-Kraemer, Christof Vulsteke, Marleen Borms, Philip Debruyne, Wim Wynendaele, Patrick Neven. Adherence to and patient satisfaction with the combination therapy of exemestane and everolimus in postmenopausal women with HR+ HER2- advanced breast cancer: Results from the IPSOC-mamma study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-06.

Background: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. Patients and methods: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8 mg/kg loading dose, then 6 mg/kg every 3 weeks (q3w)] and pertuzumab (840 mg loading dose, then 420 mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54 years; 29% had received prior trastuzumab. Median treatment duration was 16 months for pertuzumab and trastuzumab and 4 months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1 months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). Conclusions: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile.

BACKGROUND:Referral to specialized palliative care services (SPCS) occurs often late in the illness trajectory but may differ across cancer types. We examined differences between cancer types in the use and timing of referral to specialized palliative care services (SPCS) and in the reasons for non-referral.METHODS:We conducted a population-based mortality follow-back survey among physicians who certified a representative sample of deaths in Flanders, Belgium. We focused only on sampled death cases of cancer (n = 2392). The questionnaire asked about the use of the existing types of SPCS and the timing of referral to these services.RESULTS:Response rate was 58% (1394/2392). Patients who died from breast, respiratory, head and neck, genitourinary or gastrointestinal cancer had higher chances of using SPCS compared to hematologic cancer patients. The most prevalent reason for non-referral was that regular care sufficiently addressed palliative and supportive care needs (51%). This differed significantly between cancer types ranging from 77,8% for breast cancer and 42.1% for hematologic cancer. A second prevalent reason for not using SPCS was that it was not meaningful (enough) (23.9%), particularly for hematologic malignancies (35,1%) and only in 5.3% for breast cancer.CONCLUSION:Differences in referral across different types of cancer were found. Referral is more often delayed or not initiated for patients with hematologic cancer, possibly due to differences in illness trajectory. An influencing reason is that physicians perceive palliative care as not meaningful or not meaningful enough for these patients which may be linked to the uncertainty in the disease trajectory of hematologic malignancies.

We applaud the work done by Vanbutsele and colleagues 1 Vanbutsele G Pardon K Van Belle S et al. Effect of early and systematic integration of palliative care in patients with advanced cancer: a randomised controlled trial. Lancet Oncol. 2018; 19: 394-404 Summary Full Text Full Text PDF PubMed Scopus (212) Google Scholar using a highly complex palliative care intervention. However, the results are difficult to interpret, because of multiple confounders. Here, we present a couple of discussion points regarding this. Effect of early and systematic integration of palliative care in patients with advanced cancer: a randomised controlled trialThe findings of this study show that a model of early and systematic integration of palliative care in oncological care increases the quality of life of patients with advanced cancer. Our findings also show that early and systematic integration of palliative care is more beneficial for patients with advanced cancer than palliative care consultations offered on demand, even when psychosocial support has already been offered. Through integration of care, oncologists and specialised palliative care teams should work together to enhance the quality of life of patients with advanced cancer. Full-Text PDF Effect of early palliative care: complex intervention and complex results – Authors' replyWe would like to thank Ishiki and colleagues for their comments. They note that the primary outcome solely focused on the difference of overall quality of life (QOL) scores between both groups at 12 weeks. As stated in our article,1 the effect of intervention on the primary outcome and other outcomes was assessed by multivariate regression analyses adjusted for baseline scores. Baseline scores were, therefore, taken into account: for the same baseline score (59·7) in both groups, the usual care group scored 7·6 points lower on QOL at 12 weeks compared with that of the early palliative care group. Full-Text PDF

BACKGROUND:The benefit of early integration of palliative care into oncological care is suggested to be due to increased psychosocial support. In Belgium, psychosocial care is part of standard oncological care. The aim of this randomised controlled trial is to examine whether early and systematic integration of palliative care alongside standard psychosocial oncological care provides added benefit compared with usual care. METHODS:In this randomised controlled trial, eligible patients were 18 years or older, and had advanced cancer due to a solid tumour, an European Cooperative Oncology Group performance status of 0-2, an estimated life expectancy of 12 months, and were within the first 12 weeks of a new primary tumour or had a diagnosis of progression. Patients were randomly assigned (1:1), by block design using a computer-generated sequence, either to early and systematic integration of palliative care into oncological care, or standard oncological care alone in a setting where all patients are offered multidisciplinary oncology care by medical specialists, psychologists, social workers, dieticians, and specialist nurses. The primary endpoint was change in global health status/quality of life scale assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ C30) at 12 weeks. The McGill Quality of Life Questionnaire (MQOL), which includes the additional existential wellbeing dimension, was also used. Analysis was by intention to treat. This trial is ongoing, but closed for accrual, and is registered with ClinicalTrials.gov, number NCT01865396. FINDINGS:From April 29, 2013, to Feb 29, 2016, we screened 468 patients for eligibility, of whom 186 were enrolled and randomly assigned to the early and systematic palliative care group (92 patients) or the standard oncological care group (94). Compliance at 12 weeks was 71% (65 patients) in the intervention group versus 72% (68) in the control group. The overall quality of life score at 12 weeks, by the EORTC QLQ C30, was 54·39 (95% CI 49·23-59·56) in the standard oncological care group versus 61·98 (57·02-66·95) in the early and systematic palliative care group (difference 7·60 [95% CI 0·59-14·60]; p=0·03); and by the MQOL Single Item Scale, 5·94 (95% CI 5·50-6·39) in the standard oncological care group versus 7·05 (6·59-7·50) in the early and systematic palliative care group (difference 1·11 [95% CI 0·49-1·73]; p=0.0006). INTERPRETATION:The findings of this study show that a model of early and systematic integration of palliative care in oncological care increases the quality of life of patients with advanced cancer. Our findings also show that early and systematic integration of palliative care is more beneficial for patients with advanced cancer than palliative care consultations offered on demand, even when psychosocial support has already been offered. Through integration of care, oncologists and specialised palliative care teams should work together to enhance the quality of life of patients with advanced cancer. FUNDING:Research Foundation Flanders, Flemish Cancer Society (Kom Op Tegen Kanker).

Identification and validation of extracellular vesicle (EV)-associated biomarkers requires robust isolation and characterization protocols. We assessed the impact of some commonly implemented pre-analytical, analytical and post-analytical variables in EV research. Centrifugal filters with different membrane types and pore sizes are used to reduce large volume biofluids prior to EV isolation or to concentrate EVs. We compared five commonly reported filters for their efficiency when using plasma, urine and EV-spiked PBS. Regenerated cellulose membranes with pore size of 10 kDa recovered EVs the most efficient. Less than 40% recovery was achieved with other filters. Next, we analyzed the effect of the type of protein assays to measure EV protein in colorimetric and fluorometric kits. The fluorometric assay Qubit measured low concentration EV and BSA samples the most accurately with the lowest variation among technical and biological replicates. Lastly, we quantified Optiprep remnants in EV samples from density gradient ultracentrifugation and demonstrate that size-exclusion chromatography efficiently removes Optiprep from EVs. In conclusion, choice of centrifugal filters and protein assays confound EV analysis and should be carefully considered to increase efficiency towards biomarker discovery. SEC-based removal of Optiprep remnants from EVs can be considered for downstream applications.

Door ontwikkelingen in de medische wetenschap en techniek wordt de oncologische zorg steeds complexer en zijn steeds meer disciplines betrokken bij de vroegopsporing, diagnostiek, behandeling en follow-up van patiënten met kanker. Deze toegenomen complexiteit vraagt om specifieke kennis, ervaring en infrastructuur, maar ook om goede informatie-uitwisseling tussen de verschillende behandelaars in de zorgketen. Door toegenomen complexiteit en specialisatie kan niet alle oncologische zorg meer in alle ziekenhuizen plaatsvinden. Behandelaars en instellingen gaan daarom samenwerken in oncologische netwerken rondom expertcentra waar laagvolume hoogcomplexe zorg geconcentreerd wordt. Kwaliteitsnormen en -registraties borgen dat iedere patiënt behandeld wordt in de juiste setting door het juiste team van behandelaars en geven de oncologische teams continu feedback over de kwaliteit van de door hen geleverde oncologische zorg (spiegelinformatie). Transparantie van deze zorgkwaliteit en keuze-informatie zal ertoe leiden dat patiënten een beroep doen op hun huisarts om kwaliteitsinformatie te bespreken voorafgaand aan een verwijzing naar een medisch specialist of voorafgaand aan behandelbeslissingen.

BACKGROUND:The aim of this study was to assess whether outcome in advanced breast cancer patients is related to metabolic response to endocrine therapy determined by fluorodeoxyglucose positron-emission tomography (FDG-PET).METHODS:We retrospectively identified 21 consecutive breast cancer patients receiving endocrine therapy for metastatic disease (mean number of previous therapies 3.6±3.5). All patients had been evaluated with at least 2 FDG-PETs. The first scan was performed by initiation of endocrine therapy. The second scan was performed after a mean of 3.8±1.14 months. Seventy-two FDG-avid lesions were identified and followed. The mean change in SUVmax (ΔSUVmax) was calculated per patient.RESULTS:ΔSUVmax dichotomized using the group median as cut-off (8.6%) was predictive of progression-free survival (PFS). The median PFS for the response-group (N.=10, median ΔSUVmax -20.9%) was 10.1 months. The median PFS for the progressive disease-group (N.=11, median ΔSUVmax 40.6%) was 6.7 months (log-rank testing P=0.033).CONCLUSIONS:Our data suggest that breast cancer patients under hormonal therapy with stable disease on FDG-PET have a longer PFS when compared to non-responders. This finding is new, supporting the value of endocrine therapy among patients with advanced breast cancer.