Evaluating comprehensive cancer networks; a review of standards and evaluation methods for care networks to inform a comparison with the OECI comprehensive cancer network standards.

INTRODUCTION: To ensure that all citizens have equal access to high-quality cancer diagnosis and care, the EU4Health Programme, Europe's Beating Cancer Plan, and Horizon Europe's Cancer Mission propose Comprehensive Cancer Infrastructures in every European Union Member State. It is therefore important to establish the basic principles for high-performing cancer networks and a methodology for evaluating their quality and effectiveness. This article describes methods and standards/indicators for network evaluation found in literature, gives a comparative overview of the new OECI European Cancer Network Quality standards, and proposes principles for evaluating the performance of Comprehensive Cancer Networks as a basis for continuous improvement. MATERIALS AND METHODS: We performed a scoping literature review on methods and standards/indicators for care-network evaluation. We then compared the OECI set with literature findings, categorised standards that were similar, reflected on standards that were different, and deduced principles for quality standards for cancer networks. RESULTS: Of 1002 articles identified, 17 reported on evaluation methods and/or (mostly) qualitative indicators. Sixteen studies described indicators/standards for evaluating care networks, critical success factors or desirable outcomes. Of the 54 present OECI standards, 32 had a literature equivalent. No literature equivalent was found for 22 standards, especially on those related to the combination of care and research. The proposed OECI evaluation methods (survey, document review, and interviews) were all reported in the literature. From the conformity of these results, we deduced 8 principles for standards evaluating the effectiveness of Comprehensive Cancer Networks. CONCLUSIONS: Research on the evaluation of the effectiveness of care networks is scarce. Evaluation methods vary and are often single time-point assessments. The OECI set contributes to establishing clear principles and standards to evaluate the effectiveness of Comprehensive Cancer Networks.

Analysing the attributes of Comprehensive Cancer Centres and Cancer Centres across Europe to identify key hallmarks.

There is a persistent variation in cancer outcomes among and within European countries suggesting (among other causes) inequalities in access to or delivery of high-quality cancer care. European policy (EU Cancer Mission and Europe's Beating Cancer Plan) is currently moving towards a mission-oriented approach addressing these inequalities. In this study, we used the quantitative and qualitative data of the Organisation of European Cancer Institutes' Accreditation and Designation Programme, relating to 40 large European cancer centres, to describe their current compliance with quality standards, to identify the hallmarks common to all centres and to show the distinctive features of Comprehensive Cancer Centres. All Comprehensive Cancer Centres and Cancer Centres accredited by the Organisation of European Cancer Institutes show good compliance with quality standards related to care, multidisciplinarity and patient centredness. However, Comprehensive Cancer Centres on average showed significantly better scores on indicators related to the volume, quality and integration of translational research, such as high-impact publications, clinical trial activity (especially in phase I and phase IIa trials) and filing more patents as early indicators of innovation. However, irrespective of their size, centres show significant variability regarding effective governance when functioning as entities within larger hospitals.

Low-grade dysplasia in Barrett's esophagus: overdiagnosed and underestimated.

OBJECTIVES: Published data on the natural history of low-grade dysplasia (LGD) in Barrett's esophagus (BE) are inconsistent and difficult to interpret. We investigated the natural history of LGD in a large community-based cohort of BE patients after reviewing the original histological diagnosis by an expert panel of pathologists. METHODS: Histopathology reports of all patients diagnosed with LGD between 2000 and 2006 in six non-university hospitals were reviewed by two expert pathologists. This panel diagnosis was subsequently compared with the histological outcome during prospective endoscopic follow-up. RESULTS: A diagnosis of LGD was made in 147 patients. After pathology review, 85% of the patients were downstaged to non-dysplastic BE (NDBE) or to indefinite for dysplasia. In only 15% of the patients was the initial diagnosis LGD. Endoscopic follow-up was carried out in 83.6% of patients, with a mean follow-up of 51.1 months. For patients with a consensus diagnosis of LGD, the cumulative risk of progressing to high-grade dysplasia or carcinoma (HGD or Ca) was 85.0% in 109.1 months compared with 4.6% in 107.4 months for patients downstaged to NDBE (P<0.0001). The incidence rate of HGD or Ca was 13.4% per patient per year for patients in whom the diagnosis of LGD was confirmed. For patients downstaged to NDBE, the corresponding incidence rate was 0.49%. CONCLUSIONS: LGD in BE is an overdiagnosed and yet underestimated entity in general practice. Patients diagnosed with LGD should undergo an expert pathology review to purify this group. In case the diagnosis of LGD is confirmed, patients should undergo strict endoscopic follow-up or should be considered for endoscopic ablation therapy.

Increased survival of non low-grade and deep-seated soft tissue sarcoma after surgical management in high-volume hospitals: a nationwide study from the Netherlands.

BACKGROUND: Diagnosing and treating soft tissue sarcomas (STSs) remains challenging, stressing the urgency for centralisation. This nationwide survey aimed to evaluate the centralisation of STS surgery and its effect on survival. METHODS: Patients operated for primary STS from 2006 to 2015 were queried from the Netherlands Cancer Registry. Hospitals in which STS surgery was performed were allocated into three categories: low-volume (1-9 resections per year), medium-volume (10-19 resections) or high-volume (≥20 resections). Differences in tumour characteristics and outcome were calculated. A multivariable regression analysis was performed to adjust for case-mix. RESULTS: Of the 5282 identified patients, 42% was treated in low-volume hospitals, 7.7% in medium-volume hospitals and 51% in high-volume hospitals, with a significant trend over time towards treatment in a high-volume hospital (p < 0.01). In high-volume hospitals, more often patients with non low-grade, large and deep-seated tumours were treated than in low-volume hospitals. For the whole group, there was no survival benefit for patients treated in high-volume hospitals, with 10-year net survival rates of 76% (low-volume), 68% (medium-volume) and 68% (high-volume). However, subgroup analysis for patients with non low-grade and deep-seated tumours did reveal a benefit from treatment in a high-volume hospitals with 10-year survival rates of 54% (high-volume), 49% (low-volume) and 42% (medium-volume) and a relative risk of 1.3 (high-volume versus low-volume, p = 0.03). CONCLUSION: Centralisation of STS surgery has increased in the past decade. Surgery in a high-volume hospital improved survival of patients with non low-grade and deep-seated tumours, and therefore these patients should be referred to such a hospital.

High-volume versus low-volume for esophageal resections for cancer: the essential role of case-mix adjustments based on clinical data.

BACKGROUND: Most studies addressing the volume-outcome relationship in complex surgical procedures use hospital mortality as the sole outcome measure and are rarely based on detailed clinical data. The lack of reliable information about comorbidities and tumor stages makes the conclusions of these studies debatable. The purpose of this study was to compare outcomes for esophageal resections for cancer in low- versus high-volume hospitals, using an extensive set of variables concerning case-mix and outcome measures, including long-term survival. METHODS: Clinical data, from 903 esophageal resections performed between January 1990 and December 1999, were retrieved from the original patients' files. Three hundred and forty-two patients were operated on in 11 low-volume hospitals (<7 resections/year) and 561 in a single high-volume center. RESULTS: Mortality and morbidity rates were significantly lower in the high-volume center, which had an in-hospital mortality of 5 vs 13% (P < .001). On multivariate analysis, hospital volume, but also the presence of comorbidity proved to be strong prognostic factors predicting in-hospital mortality (ORs 3.05 and 2.34). For stage I and II disease, there was a significantly better 5-year survival in the high-volume center. (P = .04). CONCLUSIONS: Hospital volume and comorbidity patterns are important determinants of outcome in esophageal cancer surgery. Strong clinical endpoints such as in-hospital mortality and survival can be used as performance indicators, only if they are joined by reliable case-mix information.

Participation of Italian Cancer Centres of the Alleanza Contro Il Cancro (ACC) in the Organisation of European Cancer Institutes (OECI) Accreditation and Designation program: a successful first national initiative.

The Organisation of European Cancer Institutes (OECI) launched a program for accreditation and designation (A&D) of cancer centers in Europe based on voluntary participation in 2008. In 2012, the Italian Ministry of Health decided to fund cancer centers in Italy, members of the Alleanza Contro il Cancro (ACC), to go through the OECI accreditation program. Ten centers participated in the program and 10 completed the full cycle of the OECI A&D process in consecutive series over a 2-year period. The process was successfully completed within the planned timeline and the overall findings were presented to the Italian Ministry of Health and representatives of all the participating centers in November 2015. The program had a considerable team-building effect, which will likely continue as the improvement plans are implemented. Centers fed back to OECI that the A&D program had led to better formal organization of multidisciplinary teams (MDTs) and cancer care pathways, and had helped them to harmonize the integration of research into clinical practice. Centers also concluded that they benefited from recognition through an international accreditation system, and that it had led to them developing better patient information and involvement. The importance of the improvement plans that each center had to produce following the audit reviews cannot be underestimated. The OECI concludes that implementation of the A&D program at the national level is feasible despite national peculiarities related to health planning and organization in each member state. This is a good example of an EU project working well, with member states helping each other and learning from best practice, to improve the overall quality of cancer care and research and to establish consistency. The initial accreditation is the first part of an ongoing process of improving comprehensive cancer care, integrating bench to bedside.

Altered expression patterns of VEGF receptors in human diabetic retina and in experimental VEGF-induced retinopathy in monkey.

PURPOSE: The vascular endothelial growth factor (VEGF) family is involved in vascular leakage and angiogenesis in diabetic retinopathy (DR) in the eye, but may also have physiological functions. Based on the hypothesis that differential VEGF receptor (VEGFR) expression in the retina is an important determinant of effects of VEGF, this study was conducted to investigate VEGFR expression in the diabetic retina and in an experimental monkey model of VEGF-A-induced retinopathy. METHODS: In retinas of 27 eyes of diabetic donors, 18 eyes of nondiabetic control donors, and 4 monkey eyes injected with PBS or VEGF-A, expression patterns of VEGFR-1, -2, and -3 in relation to leaky microvessels, as identified by the marker pathologische anatomie Leiden-endothelium (PAL-E) were studied by immunohistochemistry. RESULTS. In control human retinas and retinas of PBS-injected monkey eyes, all three VEGFRs were expressed in nonvascular areas, but only VEGFR-1 was constitutively expressed in retinal microvessels. In diabetic eyes, increased microvascular VEGFR-2 expression was found in association with PAL-E expression, whereas microvascular VEGFR-3 was present in a subset of PAL-E-positive cases. In VEGF-A-injected monkey eyes, VEGFR-1, -2, and -3 and PAL-E were expressed in retinal microvessels. CONCLUSIONS: The VEGFR-1, -2, and -3 expression patterns in control retinas suggest physiological functions of VEGFs that do not involve the vasculature. Initial vascular VEGF signaling may act primarily through VEGFR-1. In diabetic eyes, expression of retinal VEGFR-2 and -3 is increased, mainly in leaky microvessels, and VEGF-A induces vascular expression of the VEGF-A receptor VEGFR-2 and the VEGF-C/D receptor VEGFR-3. These findings indicate a dual role of VEGFs in the physiology and pathophysiology of the retina and suggest that microvascular VEGFR-2 and -3 signaling by VEGFs occurs late in the pathogenesis of DR, possibly initiated by high levels of VEGF-A in established nonproliferative DR.

Basic fibroblast growth factor, glutamine synthetase, and interleukin-6 in vitreous fluid from eyes with retinal detachment complicated by proliferative vitreoretinopathy.

PURPOSE: To investigate the presence of basic fibroblast growth factor (bFGF), glutamine synthetase (GS), and interleukin-6 (IL-6) in vitreous fluid from eyes with retinal detachment complicated by proliferative vitreoretinopathy (PVR). DESIGN: Comparative case series; experimental study. METHODS: In a prospective study, we measured bFGF, GS, IL-6, and total protein in vitreous fluid samples from 53 eyes from 53 consecutive patients with PVR operated on in our hospital. As controls, vitreous fluid samples from eyes with a macular hole (n = 9) or pucker (n = 11) were used. MAIN OUTCOME MEASURES: Laboratory data of the patient group were compared with the control group and correlated with various clinical data, especially with visual recovery and redetachment. RESULTS: For IL-6, bFGF, and total protein we found significantly higher levels in PVR patients' eyes than in control eyes (P =.03, P =.046, and P <.0001, respectively). Within the PVR group, no significant correlation was found for IL-6, bFGF, GS, or total protein with the various tested clinical variables. CONCLUSIONS: We found increased levels of IL-6, bFGF, and total protein in vitreous fluid from patients' eyes with PVR. Whether the increased levels of IL-6, bFGF, and total protein are the result of an injury-induced upregulation of these proteins as part of a self-protective mechanism of the retina to minimize photoreceptor damage after the mechanical injury induced by retinal detachment is, at present, not known.