Vaginal changes, sexual functioning and distress of women with locally advanced cervical cancer treated in the EMBRACE vaginal morbidity substudy.

OBJECTIVE: The EMBRACE-vaginal morbidity substudy prospectively evaluated physician-assessed vaginal changes and patient-reported-outcomes (PRO) on vaginal and sexual functioning problems and distress in the first 2-years after image-guided radio(chemo)therapy and brachytherapy for locally advanced cervical cancer. METHODS: Eligible patients had stage IB1-IIIB cervical cancer with ≤5 mm vaginal involvement. Assessment of vaginal changes was graded using CTCAE. PRO were assessed using validated Quality-of-Life and sexual questionnaires. Statistical analysis included Generalized-Linear-Mixed-Models and Spearman's rho-correlation coefficients. RESULTS: 113 eligible patients were included. Mostly mild (grade 1) vaginal changes were reported over time in about 20% (range 11-37%). At 2-years, 47% was not sexually active. Approximately 50% of the sexually active women reported any vaginal and sexual functioning problems and distress over time; more substantial vaginal and sexual problems and distress were reported by up to 14%, 20% and 8%, respectively. Physician-assessed vaginal changes and PRO sexual satisfaction differed significantly (p ≤ .05) between baseline and first follow-up, without further significant changes over time. No or only small associations between physician-assessed vaginal changes and PRO vaginal functioning problems and sexual distress were found. CONCLUSIONS: Mild vaginal changes were reported after image-guided radio(chemo)therapy and brachytherapy, potentially due to the combination of tumors with limited vaginal involvement, EMBRACE-specific treatment optimization and rehabilitation recommendations. Although vaginal and sexual functioning problems and sexual distress were frequently reported, the rate of substantial problems and distress was low. The lack of association between vaginal changes, vaginal functioning problems and sexual distress shows that sexual functioning is more complex than vaginal morbidity alone.

Brachytherapy treatment verification using gamma radiation from the internal treatment source combined with an imaging panel-a phantom study.

Brachytherapy has an excellent clinical outcome for different treatment sites. However,in vivotreatment verification is not performed in the majority of hospitals due to the lack of proper monitoring systems. This study investigates the use of an imaging panel (IP) and the photons emitted by a high dose rate (HDR)192Ir source to track source motion and obtain some information related to the patient anatomy. The feasibility of this approach was studied by monitoring the treatment delivery to a 3D printed phantom that mimicks a prostate patient. A 3D printed phantom was designed with a template for needle insertion, a cavity ('rectum') to insert an ultrasound probe, and lateral cavities used to place tissue-equivalent materials. CT images were acquired to create HDR192Ir treatment plans with a range of dwell times, interdwell distances and needle arrangements. Treatment delivery was verified with an IP placed at several positions around the phantom using radiopaque markers on the outer surface to register acquired IP images with the planning CT. All dwell positions were identified using acquisition times ≤0.11 s (frame rates ≥ 9 fps). Interdwell distances and dwell positions (in relation to the IP) were verified with accuracy better than 0.1 cm. Radiopaque markers were visible in the acquired images and could be used for registration with CT images. Uncertainties for image registration (IP and planning CT) between 0.1 and 0.4 cm. The IP is sensitive to tissue-mimicking insert composition and showed phantom boundaries that could be used to improve treatment verification. The IP provided sufficient time and spatial resolution for real-time source tracking and allows for the registration of the planning CT and IP images. The results obtained in this study indicate that several treatment errors could be detected including swapped catheters, incorrect dwell times and dwell positions.

Clinical and imaging findings in cervical cancer and their impact on FIGO and TNM staging - An analysis from the EMBRACE study.

OBJECTIVE: To investigate differences in local tumour staging between clinical examination and MRI and differences between FIGO 2009, FIGO 2018 and TNM in patients with primary cervical cancer undergoing definitive radio-chemotherapy. METHODS: Patients from the prospective observational multi-centre study "EMBRACE" were considered for analysis. All patients had gynaecological examination and pelvic MRI before treatment. Nodal status was assessed by MRI, CT, PET-CT or lymphadenectomy. For this analysis, patients were restaged according to the FIGO 2009, FIGO 2018 and TNM staging system. The local tumour stage was evaluated for MRI and clinical examination separately. Descriptive statistics were used to compare local tumour stages and different staging systems. RESULTS: Data was available from 1338 patients. For local tumour staging, differences between MRI and clinical examination were found in 364 patients (27.2%). Affected lymph nodes were detected in 52%. The two most frequent stages with FIGO 2009 are IIB (54%) and IIIB (16%), with FIGO 2018 IIIC1 (43%) and IIB (27%) and with TNM T2b N0 M0 (27%) and T2b N1 M0 (23%) in this cohort. CONCLUSIONS: MRI and clinical examination resulted in a different local tumour staging in approximately one quarter of patients. Comprehensive knowledge of the differential value of clinical examination and MRI is necessary to define one final local stage, especially when a decision about treatment options is to be taken. The use of FIGO 2009, FIGO 2018 and TNM staging system leads to differences in stage distributions complicating comparability of treatment results. TNM provides the most differentiated stage allocation.

Automatic Quality Assessment of Transperineal Ultrasound Images of the Male Pelvic Region, Using Deep Learning.

Ultrasound guidance is not in widespread use in prostate cancer radiotherapy workflows. This can be partially attributed to the need for image interpretation by a trained operator during ultrasound image acquisition. In this work, a one-class regressor, based on DenseNet and Gaussian processes, was implemented to automatically assess the quality of transperineal ultrasound images of the male pelvic region. The implemented deep learning approach was tested on 300 transperineal ultrasound images and it achieved a scoring accuracy of 94%, a specificity of 95% and a sensitivity of 92% with respect to the majority vote of 3 experts, which was comparable with the results of these experts. This is the first step toward a fully automatic workflow, which could potentially remove the need for ultrasound image interpretation and make real-time volumetric organ tracking in the radiotherapy environment using ultrasound more appealing.

Flemish breast cancer screening programme: 15 years of key performance indicators (2002-2016).

BACKGROUND: We examined 15 years of key performance indicators (KPIs) of the population-based mammography screening programme (PMSP) in Flanders, Belgium. METHODS: Individual screening data were linked to the national cancer registry to obtain oncological follow-up. We benchmarked crude KPI results against KPI-targets set by the European guidelines and KPI results of other national screening programmes. Temporal trends were examined by plotting age-standardised KPIs against the year of screening and estimating the Average Annual Percentage Change (AAPC). RESULTS: PMSP coverage increased significantly over the period of 15 years (+ 7.5% AAPC), but the increase fell to + 1.6% after invitation coverage was maximised. In 2016, PMSP coverage was at 50.0% and opportunistic coverage was at 14.1%, resulting in a total coverage by screening of 64.2%. The response to the invitations was 49.8% in 2016, without a trend. Recall rate decreased significantly (AAPC -1.5% & -5.0% in initial and subsequent regular screenings respectively) while cancer detection remained stable (AAPC 0.0%). The result was an increased positive predictive value (AAPC + 3.8%). Overall programme sensitivity was stable and was at 65.1% in 2014. In initial screens of 2015, the proportion of DCIS, tumours stage II+, and node negative invasive cancers was 18.2, 31.2, and 61.6% respectively. In subsequent regular screens of 2015, those proportions were 14.0, 24.8, and 65.4% respectively. Trends were not significant. CONCLUSION: Besides a suboptimal attendance rate, most KPIs in the Flemish PMSP meet EU benchmark targets. Nonetheless, there are several priorities for further investigation such as a critical evaluation of strategies to increase screening participation, organising a biennial radiological review of interval cancers, analysing the effect that preceding opportunistic screening has on the KPI for initial screenings, and efforts to estimate the impact on breast cancer mortality.

Decision Support Systems in Prostate Cancer Treatment: An Overview.

BACKGROUND: A multifactorial decision support system (mDSS) is a tool designed to improve the clinical decision-making process, while using clinical inputs for an individual patient to generate case-specific advice. The study provides an overview of the literature to analyze current available mDSS focused on prostate cancer (PCa), in order to better understand the availability of decision support tools as well as where the current literature is lacking. METHODS: We performed a MEDLINE literature search in July 2018. We divided the included studies into different sections: diagnostic, which aids in detection or staging of PCa; treatment, supporting the decision between treatment modalities; and patient, which focusses on informing the patient. We manually screened and excluded studies that did not contain an mDSS concerning prostate cancer and study proposals. RESULTS: Our search resulted in twelve diagnostic mDSS; six treatment mDSS; two patient mDSS; and eight papers that could improve mDSS. CONCLUSIONS: Diagnosis mDSS is well represented in the literature as well as treatment mDSS considering external-beam radiotherapy; however, there is a lack of mDSS for other treatment modalities. The development of patient decision aids is a new field of research, and few successes have been made for PCa patients. These tools can improve personalized medicine but need to overcome a number of difficulties to be successful and require more research.

Comparison of brachytherapy and external beam radiotherapy boost in breast-conserving therapy: Patient-reported outcome measures and aesthetic outcome.

OBJECTIVE: This study aimed to estimate the probability of an unfavourable aesthetic outcome (AO) 2 years after breast-conserving therapy (BCT) and evaluate the possible influence of brachytherapy (BT) and external beam radiotherapy (EBRT) boost on patient-reported outcomes (PROs) and AO. PATIENTS AND METHODS: Patients treated with BCT starting April 2015 were prospectively included. Selection of the boost technique followed an in-house flowchart based on the depth of the tumour bed. An electron boost was performed for a superficial clinical target volume (maximum 28 mm under the epidermis), a BT boost was proposed in all other cases. Patients were followed-up for 2 years. AO was scored by the BCCT.core software and the patient. Further PROs were measured with the EORTC QLQ-C30, QOL-BR23 and the BIBCQ questionnaires. RESULTS: The analysis included 175 patients, 80 received a BT boost and 95 an EBRT boost. BT patients were significantly older; had a higher breast cup and band size, body mass index and surgical specimen weight of the wide excision; more seroma at baseline and less positive surgical section margins than patients in the EBRT group, and more patients drank alcohol. Cancer- and breast cancer-specific quality of life (QOL) and body image did not differ between the boost techniques over time. Although mean scores for breast symptoms and sexual enjoyment did differ significantly over time (p = 0.05 and < 0.01, respectively), the effect was due to differences before boost administration. Measured with BCCT.core, AO was unfavourable in 28% of patients 2 years after treatment (31% scored by the patient) and results were similar in the BT and EBRT groups. CONCLUSION: Using the presented flowchart (See Verhoeven et al. [16]), AO and PROs on QOL or body image up to 2 years after BCT are not influenced by the boost technique.

Radiobiology of brachytherapy: The historical view based on linear quadratic model and perspectives for optimization.

Most preclinical studies examining the radiobiology of brachytherapy have focused on dose rate effects. Scarcer data are available on other major parameters of therapeutic index, such as cell cycle distribution, repopulation or reoxygenation. The linear quadratic model describes the effect of radiotherapy in terms of normal tissue or tumour response. It allows some comparisons between various irradiation schemes. This model should be applied cautiously for brachytherapy, because it relies on cell death analysis only, and therefore partially reflects the biological effects of an irradiation. Moreover, the linear quadratic model validity has not been demonstrated for very high doses per fraction. A more thorough analysis of mechanisms involved in radiation response is required to better understand the true effect of brachytherapy on normal tissue. The modulation of immune response is one promising strategy to be tested with brachytherapy. A translational approach applied to brachytherapy should lead to design trials testing pharmacological agents modulating radiation response, in order to improve not only local control, but also decrease the risk of distant failure. Here we review the radiobiology of brachytherapy, from the historical view based on linear quadratic model to recent perspectives for biological optimization.

Breast cancer subtype and survival by parity and time since last birth.

BACKGROUND: Pregnancy affects breast cancer risk but how it affects the subtype and prognosis remain controversial. We studied the effect of parity and time since last birth on breast cancer subtype and outcome. PATIENTS AND METHODS: We conducted a retrospective multivariate cohort study including all premenopausal women with early breast cancer aged ≤ 50 years (N = 1306) at diagnosis at the University Hospitals Leuven (Jan. 2000-Dec. 2009). Primary study endpoints were the breast cancer subtype, disease-free survival, and distant disease-free survival by parity and time since last birth. Statistical methods used were baseline-category logits models and Cox proportional hazard models. Multivariable models were used to correct for possible confounders. RESULTS: Breast cancer subtypes did not differ between nulliparous (N = 266) and parous women (N = 1040) but subtypes differed significantly in parous women by time since last birth (p < 0.001). Tumors within 5 years of last birth were proportionally more likely triple negative and HER-2 like, even when corrected for age at diagnosis. After a mean follow-up period of 10 years, parous women had a better disease-free survival compared to nulliparous women (HR 0.733; CI 0.560-0.961; p = 0.025, HR 0.738; CI 0.559-0.974; p = 0.032 before and after correction for known prognostic factors, respectively). In parous women, a longer time since last birth was correlated with a longer disease-free survival compared to patients with a recent pregnancy (HR 0.976; CI 0.957-0.996; p = 0.018). However, after correction, this association completely disappeared (HR 1.010; CI 0.982-1.040; p = 0.480). CONCLUSION: We observed a better disease-free survival for parous than nulliparous women. The influence of recent birth on disease-free survival is probably due to tumor and patient characteristics, as recent birth is associated with more aggressive subtypes.

Body mass index, age at breast cancer diagnosis, and breast cancer subtype: a cross-sectional study.

PURPOSE: Evidence suggests that premenopausal obesity decreases and postmenopausal obesity increases breast cancer risk. Because it is not well known whether this is subtype dependent, we studied the association between body mass index (BMI) and age at breast cancer diagnosis, or the probability of being diagnosed with a specific breast cancer phenotype, by menopausal status. METHODS: All patients with non-metastatic operable breast cancer from the University Hospital Leuven diagnosed between January 1, 2000 and December 31, 2013 were included (n = 7020) in this cross-sectional study. Linear models and logistic regression were used for statistical analysis. Allowing correction for age-related BMI-increase, we used the age-adjusted BMI score which equals the difference between a patient's BMI score and the population-average BMI score corresponding to the patient's age category. RESULTS: The quadratic relationship between the age-adjusted BMI and age at breast cancer diagnosis (p = 0.0207) interacted with menopausal status (p < 0.0001); increased age at breast cancer diagnosis was observed with above-average BMI scores in postmenopausal women, and with below-average BMI scores in premenopausal women. BMI was linearly related to the probabilities of Luminal B and HER2-like breast cancer phenotypes, but only in postmenopausal women. The relative changes in probabilities between both these subtypes mirrored each other. CONCLUSION: BMI associates differently before and after menopause with age at breast cancer diagnosis and with the probability that breast cancer belongs to a certain phenotype. The opposite effect of increasing BMI on relative frequencies of Luminal B and HER2-like breast cancers suggests a common origin.

Dynamics of rectal balloon implant shrinkage in prostate VMAT : Influence on anorectal dose and late rectal complication risk.

PURPOSE: To assess the effect of a shrinking rectal balloon implant (RBI) on the anorectal dose and complication risk during the course of moderately hypofractionated prostate radiotherapy. METHODS: In 15 patients with localized prostate cancer, an RBI was implanted. A weekly kilovolt cone-beam computed tomography (CBCT) scan was acquired to measure the dynamics of RBI volume and prostate-rectum separation. The absolute anorectal volume encompassed by the 2 Gy equieffective 75 Gy isodose (V75Gy) was recalculated as well as the mean anorectal dose. The increase in estimated risk of grade 2-3 late rectal bleeding (LRB) between the start and end of treatment was predicted using nomograms. The observed acute and late toxicities were evaluated. RESULTS: A significant shrinkage of RBI volumes was observed, with an average volume of 70.4% of baseline at the end of the treatment. Although the prostate-rectum separation significantly decreased over time, it remained at least 1 cm. No significant increase in V75Gy of the anorectum was observed, except in one patient whose RBI had completely deflated in the third week of treatment. No correlation between mean anorectal dose and balloon deflation was found. The increase in predicted LRB risk was not significant, except in the one patient whose RBI completely deflated. The observed toxicities confirmed these findings. CONCLUSIONS: Despite significant decrease in RBI volume the high-dose rectal volume and the predicted LRB risk were unaffected due to a persistent spacing between the prostate and the anterior rectal wall.

Omitting radiation therapy in women with triple-negative breast cancer leads to worse breast cancer-specific survival.

PURPOSE: To examine locoregional recurrence (LRR) and breast cancer-specific survival (BCSS) after breast-conserving therapy (BCT) or mastectomy (ME) with or without radiation therapy (RT) in triple-negative breast cancer (TNBC). MATERIAL & METHODS: We identified non-metastatic TNBC cases from a single institution database. BCT, ME with RT (ME + RT) and ME only were compared with respect to LRR and BCSS. Cox regression models were used to analyze the association between prognostic factors and outcome. RESULTS: 439 patients fulfilled the inclusion criteria. Median follow-up was 10.2 years (interquartile range 7.9; 12.4 years). Patients in the BCT (n = 239), ME + RT (n = 116) and ME only (n = 84) group differed with respect to age, pT, pN, lymphovascular invasion, lymph node dissection and chemotherapy administration. Ten-year LRR rates were seven percent, three percent and eight percent for the BCT, ME + RT and ME only group, respectively. pN was associated with LRR. In multivariable analysis LRR were significantly lower in the ME + RT group compared to the BCT and the ME only group (p 0.037 and 0.020, respectively). Ten year BCSS was 87%, 84% and 75% for the BCT, ME + RT and ME only group, respectively. pT, pN, lymph node dissection, lymphovascular invasion and the administration of chemotherapy were associated with BCSS. In multivariable analysis BCSS was significantly lower in the ME only group compared to the BCT group and the ME + RT group (p 0.047 and 0.003, respectively). CONCLUSION: TNBC patients treated with ME without adjuvant RT showed significant lower BCSS compared to patients treated with BCT or ME + RT and significant more LRR compared to ME + RT when corrected for known clinicopathological prognostic factors.

First results of the Flemish colorectal cancer screening program : start-up- period late 2013.

BACKGROUND AND AIMS: Investigation of the first participation rate and follow-up results of the Flemish colorectal cancer screening program. PATIENTS AND METHODS: In 2013 five age cohorts with an even age between 66 and 74 year old (n=243 335) were invited by mail to return a completed iFOBT. Participants who tested positive (≥75ng/ml) were referred to a follow-up colonoscopy. RESULTS: Participation rate was 48.4% (n=117 774). Overall positivity rate was 10.1%, and 78.1% of those tested positive underwent a colonoscopy. The positive predictive value of colonoscopy for CRC was 8.2%, for advanced adenoma 16.9% and for non-advanced adenoma 36.5%. CONCLUSIONS: Based on the EU-guidelines 35% was expected as participation for a first screening round, thus a participation rate of 48.4% is more than acceptable for a first screening year. The high positivity rate can partly be explained by including only the older ages in the start-up-period and by the first year of mass screening in Flanders. (Acta gastroenterol. belg., 2016, 79, 421-428).

Quantifying independent risk factors for failing to rescreen in a breast cancer screening program in Flanders, Belgium.

BACKGROUND: Mammographic screening may reduce breast cancer mortality by about 20%, provided participation is high and women screen regularly. We quantified independent risk factors for failing to rescreen and built a model to predict how rescreening rates change if these risk factors would be modified. METHODS: Multivariate analysis was used to analyze data from a prospective study which included a self-administered questionnaire and rescreening status 30months after a t0 mammogram, using a random sample of women 50-67years (Belgium 2010-2013). RESULTS: A false positive result at the most recent past mammogram (Odds Ratio=5.0, 95% Confidence Interval 3.6-6.8), an interval until new invitation greater than 25months (Odds Ratio=4.8 for >29months, 95% Confidence Interval 2.9-8.1), waiting times in the mammography unit >1h (Odds Ratio=2.1, 95% Confidence Interval 1.2-3.7) and difficulties in reaching the unit (Odds Ratio=2.5, 95% Confidence Interval 1.4-4.4) were the strongest independent predictors for failing to rescreen. The area under the curve of the receiver operating characteristic analysis was 0.705 for the model development stage and 0.717 for the validation stage and goodness-of-fit was good. CONCLUSIONS: Maintaining an invitation cycle of maximum 25months, limiting waiting time in the mammography unit and lowering the number of false positives could increase breast cancer screening compliance.

A prospective assessment of musculoskeletal toxicity and loss of grip strength in breast cancer patients receiving adjuvant aromatase inhibitors and tamoxifen, and relation with BMI.

Aromatase inhibitor (AI) therapy for estrogen receptor-positive breast cancer is known to induce or enhance musculoskeletal problems. We have previously reported that loss of grip strength is more pronounced in AI-users with extremes in BMI. We here report results from a larger prospective study. Postmenopausal early breast cancer patients scheduled to start AI or tamoxifen therapy were recruited. A functional assessment grip strength test was performed at baseline, 3, 6, and 12 months of therapy. BMI was assessed, and a rheumatologic questionnaire was completed at each visit. 188 patients on an AI and 104 patients on tamoxifen were enrolled. 74 % of AI-users reported new/worsened musculoskeletal complaints compared with 37 % in the tamoxifen group. This was translated in a larger grip strength decrease in patients experiencing AI-induced pain opposed to patients without new/worsened complaints (p = 0.0002). 15 % of AI-users discontinued therapy due to musculoskeletal symptoms, who were characterized by a larger grip strength reduction versus adherent patients (p = 0.0107). Young age (p = 0.0135), taxane-based chemotherapy (p = 0.0223), and baseline VAS score >4 (p = 0.0155) were predictors for AI-related musculoskeletal pain. In addition, a quadratic trend of BMI with grip strength change (p = 0.0090) and probability of discontinuation was observed (p = 0.0424). Musculoskeletal events were a substantial problem in AI-treated patients and an important reason for treatment discontinuation. The decrease in grip strength was larger in AI- than in tamoxifen-users, with a more pronounced change in symptomatic patients. The inverse relationship between BMI extremes and grip strength change was confirmed in this large group of AI-patients.

HPV-related oropharyngeal cancers in Flanders (Belgium): a multicenter study.

INTRODUCTION: Human papilloma virus (HPV) was recently reported to play a major role in oropharyngeal carcinoma. Large geographical differences in the disease prevalence have been described. Until now, no data have been reported for Flanders (Belgium). METHODS: A multicenter cooperative study was undertaken at the radiation-oncology departments of Flemish universities. Tumor blocks from patients diagnosed with oropharyngeal carcinoma between 2000 and 2010 were tested for HPV at a single center. Patients' characteristics, treatments, and follow-up data were recorded from medical files. Age standardized incidence rates of oropharyngeal carcinoma were collected from the Belgian Cancer Registry. RESULTS AND CONCLUSIONS: The incidence of oropharyngeal carcinoma has increased in males and females. Tissues were collected from 264 patients and the HPV status could be defined in 249 of them. The prevalence of HPV(+) oropharyngeal carcinoma was 24.78% (19.93-30.36%). In our cohort, HPV(+) tumors occurred in patients with more advanced tumor stages (p < 0.05), who smoked less (p < 0.05), consumed less alcohol (p < 0.05), had a tonsillar/base of tongue sublocalization (p < 0.05), and were older (p < 0.05). After radiotherapy, locoregional control and disease free survival were significantly better for patients with HPV(+) status (p < 0.05) in univariate analysis. HPV status remained a strong predictor of better locoregional control after multivariate analysis. We found that concurrent chemotherapy had an equal benefit for locoregional control in both HPV(+) and HPV(-) patients.

Pre-operative irradiation for retroperitoneal liposarcoma: results of a pilot study.

PURPOSE: The aim of this study was to evaluate toxicity and benefit of an original method of preoperative irradiation combined with adequate surgery in the treatment of retroperitoneal liposarcoma. Instead of irradiating the whole tumor volume, 50Gy in 25 fractions was delivered to the posterior part of the tumor and the contact zone with the postero-lateral abdominal wall only. METHODS: Between mid-2000 and end of 2011, 29 patients were included in this study, 22 with a primary tumor, 7 with a first local recurrence. The results obtained were compared with a well-matched control group operated on by the same surgeon during the same period. RESULTS: This therapy was well tolerated by all included patients and no difference in toxicity was found between pilot and control group. With a median follow-up of 84 months the oncological results were similar in both groups with a 5 y disease specific survival of 79 and 81% (p: 0.61). However a very significant difference was found according to histotype: five year disease specific survival was 84% (CI 66-93) for the well- differentiated and only 35% (CI 20-51) for the dedifferentiated liposarcoma (p < 0.0001). CONCLUSIONS: This form of combined treatment is well tolerated but superiority could not be demonstrated. Our experience clarifies some of the difficulties facing a randomized clinical trial on this topic.

Evaluation of the quality of the management of cancer of the corpus uteri--selection of relevant quality indicators and implementation in Belgium.

OBJECTIVE: Describe the methodology and selection of quality indicators (QI) to be implemented in the EFFECT (EFFectiveness of Endometrial Cancer Treatment) project. EFFECT aims to monitor the variability in Quality of Care (QoC) of uterine cancer in Belgium, to compare the effectiveness of different treatment strategies to improve the QoC and to check the internal validity of the QI to validate the impact of process indicators on outcome. METHODS: A QI list was retrieved from literature, recent guidelines and QI databases. The Belgian Healthcare Knowledge Center methodology was used for the selection process and involved an expert's panel rating the QI on 4 criteria. The resulting scores and further discussion resulted in a final QI list. An online EFFECT module was developed by the Belgian Cancer Registry including the list of variables required for measuring the QI. Three test phases were performed to evaluate the relevance, feasibility and understanding of the variables and to test the compatibility of the dataset. RESULTS: 138 QI were considered for further discussion and 82 QI were eligible for rating. Based on the rating scores and consensus among the expert's panel, 41 QI were considered measurable and relevant. Testing of the data collection enabled optimization of the content and the user-friendliness of the dataset and online module. CONCLUSIONS: This first Belgian initiative for monitoring the QoC of uterine cancer indicates that the previously used QI selection methodology is reproducible for uterine cancer. The QI list could be applied by other research groups for comparison.

Breast cancer phenotype, nodal status and palpability may be useful in the detection of overdiagnosed screening-detected breast cancers.

BACKGROUND: Breast cancer remains the leading cause of female cancer death despite improvements in treatment and screening. Screening is often criticized for leading to overdiagnosis and overtreatment. However, few have attempted to identify overdiagnosed cases. PATIENTS AND METHODS: A large, consecutive series of patients treated for primary operable, screening-detected, breast cancer (n = 1610). Details from pathology and clinical reports, treatment and follow-up were available from our prospectively managed database. Univariate and multivariate Cox proportional models were used to study the prognostic variables in screening-detected breast cancers for distant metastatic and breast cancer-specific survival. RESULTS: We included 1610 patients. The mean/median follow-up was 6.0/6.0 years. Univariate analysis: tumor size, palpability, breast cancer phenotype and nodal status were predictors of distant metastasis and breast cancer-specific death. Multivariate analysis: palpability, breast cancer phenotype and nodal status remained independent prognostic variables. Palpability differed by breast cancer phenotype. CONCLUSION: Screening-detected breast cancer is associated with excellent outcome. Palpability, nodal status and breast cancer phenotype are independent prognostic variables that may select patients at increased risk for distant metastatic relapse and breast cancer-specific death. Overdiagnosed cases reside most likely in the nonpalpable node negative subgroup with a Luminal A phenotype.

The prognostic role of preoperative and (early) postoperatively change in CA15.3 serum levels in a single hospital cohort of primary operable breast cancers.

Measuring CA15.3 serum levels in the early breast cancer setting is not recommended by current ASCO guidelines. In this large single center study, we assess the prognostic value of preoperative (n = 3746), postoperative (n = 4049) and change in (n = 3252) CA15.3, also across different breast cancer phenotypes. Preoperative, postoperative and change in CA15.3 were all significant (p = 0.0348, p < 0.0001, p < 0.0001 respectively in multivariate analysis) predictors of distant metastasis free survival. For breast cancer specific survival, only postoperative and change in CA15.3 were significant predictors (p < 0.0001 both). Multivariate prognostic models did not improve by incorporating information on preoperative CA15.3, but did improve when introducing information on postoperative CA15.3 for distant metastasis (p = 0.0365) and on change in CA15.3 for breast cancer specific survival (p = 0.0291). Change in CA15.3 impacts on prognosis (distant metastasis) differently in different breast cancer phenotypes. A decrease in CA15.3 may be informative of improved prognosis in basal like and HER2 like breast cancer.