Health-related quality of life (HRQoL) after different axillary treatments in women with breast cancer: a 1-year longitudinal cohort study.

PURPOSE: As life expectancy continues to rise, post-treatment health-related quality of life (HRQoL) of breast cancer patients becomes increasingly important. This study examined the one-year longitudinal relation between axillary treatments and physical, psychosocial, and sexual wellbeing and arm symptoms. METHODS: Women diagnosed with breast cancer who received different axillary treatments being axilla preserving surgery (APS) with or without axillary radiotherapy or full axillary lymph node dissection (ALND) with or without axillary radiotherapy were included. HRQoL was assessed at baseline, 6- and 12-months postoperatively using the BREAST-Q and the European Organization for Research and Treatment of Cancer QoL Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Mixed regression models were constructed to assess the impact of axillary treatment on HRQoL. HRQoL at baseline was compared to HRQoL at 6- and at 12-months postoperatively. RESULTS: In total, 552 patients were included in the mixed regressions models. Except for ALND with axillary radiotherapy, no significant differences in physical and psychosocial wellbeing were found. Physical wellbeing decreased significantly between baseline and 6- and 12-months postoperatively (p < 0.001, p = 0.035) and psychosocial wellbeing decreased significantly between baseline and 12 months postoperatively (p = 0.028) for ALND with axillary radiotherapy compared to APS alone. Arm symptoms increased significantly between baseline and 6 months and between baseline and 12 months postoperatively for APS with radiotherapy (12.71, 13.73) and for ALND with radiotherapy (13.93, 16.14), with the lowest increase in arm symptoms for ALND without radiotherapy (6.85, 7.66), compared to APS alone (p < 0.05). CONCLUSION: Physical and psychosocial wellbeing decreased significantly for ALND with radiotherapy compared to APS alone. Shared decision making and expectation management pre-treatment could be strengthened by discussing arm symptoms per axillary treatment with the patient.

International development of a patient-centered core outcome set for assessing health-related quality of life in metastatic breast cancer patients.

PURPOSE: For patients living with metastatic breast cancer (MBC), achieving best possible health-related quality of life, along with maximizing survival, is vital. Yet, we have no systemic way to determine if we achieve these goals. A Core Outcome Set (COS) that allows standardized measurement of outcomes important to patients, but also promotes discussing these outcomes during clinical encounters, is long overdue. METHODS: An international expert group (EG) of patient advocates, researchers, medical specialists, nurse specialists, and pharmaceutical industry representatives (n = 17) reviewed a list of relevant outcomes retrieved from the literature. A broader group (n = 141: patients/patient advocates (n = 45), health care professionals/researchers (n = 64), pharmaceutical industry representatives (n = 28), and health authority representatives (n = 4)) participated in a modified Delphi procedure, scoring the relevance of outcomes in two survey rounds. The EG finalized the COS in a consensus meeting. RESULTS: The final MBC COS includes 101 variables about: (1) health-related quality of life (HRQoL, n = 26) and adverse events (n = 24); (2) baseline patient characteristics (n = 9); and (3) clinical variables (n = 42). Many outcome that cover aspects of HRQoL relevant to MBC patients are included, e.g. daily functioning (including ability to work), psychosocial/emotional functioning, sexual functioning, and relationship with the medical team. CONCLUSION: The COS developed in this study contains important administrative data, clinical records, and clinician-reported measures that captures the impact of cancer. The COS is important for standardization of clinical research and implementation in daily practice and has received accreditation by the International Consortium for Health Outcomes Measurement (ICHOM).

De-escalation of axillary surgery in breast cancer patients treated in the neoadjuvant setting: a Dutch population-based study.

PURPOSE: An overall trend is observed towards de-escalation of axillary surgery in patients with breast cancer. The objective of this study was to evaluate this trend in patients treated with neoadjuvant systemic therapy (NST). METHODS: Patients with cT1-4N0-3 breast cancer treated with NST (2006-2016) were selected from the Netherlands Cancer Registry. Patients were classified by clinical node status (cN) and type of axillary surgery. Uni- and multivariable logistic regression analyses were performed to determine the clinicopathological factors associated with performing ALND in cN+ patients. RESULTS: A total of 12,461 patients treated with NST were identified [5830 cN0 patients (46.8%), 6631 cN+ patients (53.2%)]. In cN0 patients, an overall increase in sentinel lymph node biopsy (SLNB) only (not followed by ALND) was seen from 11% in 2006 to 94% in 2016 (p < 0.001). SLNB performed post-NST increased from 33 to 62% (p < 0.001). In cN+ patients, an overall decrease in ALND was seen from 99% in 2006 to 53% in 2016 (p < 0.001). Age (OR 1.01, CI 1.00-1.02), year of diagnosis (OR 0.47, CI 0.44-0.50), HER2-positive disease (OR 0.62, CI 0.52-0.75), clinical tumor stage (T2 vs. T1 OR 1.32, CI 1.06-1.65, T3 vs. T1 OR 2.04, CI 1.58-2.63, T4 vs. T1 OR 6.37, CI 4.26-9.50), and clinical nodal stage (N3 vs. N1 OR 1.65, CI 1.28-2.12) were correlated with performing ALND in cN+ patients. CONCLUSIONS: ALND decreased substantially over the past decade in patients treated with NST. Assessment of long-term prognosis of patients in whom ALND is omitted after NST is urgently needed.

Excision of both pretreatment marked positive nodes and sentinel nodes improves axillary staging after neoadjuvant systemic therapy in breast cancer.

BACKGROUND: Marking the axilla with radioactive iodine seed and sentinel lymph node (SLN) biopsy have been proposed for axillary staging after neoadjuvant systemic therapy in clinically node-positive breast cancer. This study evaluated the identification rate and detection of residual disease with combined excision of pretreatment-positive marked lymph nodes (MLNs) together with SLNs. METHODS: This was a multicentre retrospective analysis of patients with clinically node-positive breast cancer undergoing neoadjuvant systemic therapy and the combination procedure (with or without axillary lymph node dissection). The identification rate and detection of axillary residual disease were calculated for the combination procedure, and for MLNs and SLNs separately. RESULTS: At least one MLN and/or SLN(s) were identified by the combination procedure in 138 of 139 patients (identification rate 99·3 per cent). The identification rate was 92·8 per cent for MLNs alone and 87·8 per cent for SLNs alone. In 88 of 139 patients (63·3 per cent) residual axillary disease was detected by the combination procedure. Residual disease was shown only in the MLN in 20 of 88 patients (23 per cent) and only in the SLN in ten of 88 (11 per cent), whereas both the MLN and SLN contained residual disease in the remainder (58 of 88, 66 per cent). CONCLUSION: Excision of the pretreatment-positive MLN together with SLNs after neoadjuvant systemic therapy in patients with clinically node-positive disease resulted in a higher identification rate and improved detection of residual axillary disease.

ANTECEDENTES: En el cáncer de mama con ganglios positivos clínicamente tras el tratamiento neoadyuvante sistémico, se ha propuesto la utilización de iodo radioactivo (Marking Axilla with Radioactive Iodine, MARI) y de la biopsia de ganglio linfático centinela para la estadificación axilar. En este estudio se evaluó la tasa de identificación y detección de enfermedad residual cuando se combinó la exéresis de los ganglios linfáticos marcados antes del tratamiento (marked lymph nodes, MLN) junto con los ganglios centinela (sentinel lymph nodes, SLN). MÉTODOS: Se realizó un análisis retrospectivo multicéntrico de pacientes con cáncer de mama con ganglios positivos clínicamente que se sometieron a tratamiento neoadyuvante sistémico y en las que se combinaron ambas técnicas (con o sin disección axilar). Se calcularon las tasas de identificación y detección de enfermedad residual axilar para MLN y SLN por separado y en conjunto. RESULTADOS: En 138/139 pacientes se identificaron ≥ 1 MLN y/o SLN combinando ambas técnicas (tasa de identificación del 99,3%). La tasa de identificación fue de 92,8% para MLN y del 87,8% para SLN. Combinando ambas técnicas se detectó enfermedad axilar residual en 88/139 (63,3%) pacientes. Se detectó enfermedad residual en 20/88 (22,7%) pacientes utilizando únicamente MLN, en 10/88 (11,4%) pacientes utilizando únicamente SLN y en 58/88 (65,9%) combinando ambas técnicas. CONCLUSIÓN: La exéresis conjunta de los ganglios marcados con iodo radioactivo antes del tratamiento neoadyuvante sistémico y de los ganglios centinela después del tratamiento en pacientes con cN+ logró una tasa de identificación más alta y una mejor detección de la enfermedad axilar residual.

Patient-Reported Outcome Measures May Add Value in Breast Cancer Surgery.

PURPOSE: Considering the comparable prognosis in early-stage breast cancer after breast-conserving therapy (BCT) and mastectomy, quality of life should be a focus in treatment decision(s). We retrospectively collected PROs and analyzed differences per type of surgery delivered. We aimed to obtain reference values helpful in shared decision-making. PATIENTS AND METHODS: pTis-T3N0-3M0 patients operated between January 2005 and September 2016 were eligible if: (1) no chemotherapy was administered < 6 months prior to enrolment, and (2) identical surgeries were performed in case of bilateral surgery. After consent, EQ-5D-5L, EORTC-QLQ-C30/BR23, and BREAST-Q were administered. PROs were evaluated per baseline characteristics using multivariable linear regression models. Outcomes were compared for different surgeries as well as for primary (PBC) and second primary or recurrent (SBC) breast cancer patients using analyses of variance (ANOVAs). RESULTS: The response rate was 68%. PROs in 612 PBC patients were comparable to those in 152 SBC patients. Multivariable analyses showed increasing age to be associated with lower "physical functioning" [ß - 0.259, p < 0.001] and "sexual functioning" [ß - 0.427, p < 0.001], and increasing time since surgery with less "fatigue" [ß - 1.083, p < 0.001]. Mastectomy [ß - 13.596, p = 0.003] and implant reconstruction [ß - 13.040, p = 0.007] were associated with lower "satisfaction with breast" scores than BCT. Radiation therapy was associated with lower satisfaction scores than absence of radiotherapy. DISCUSSION: PRO scores were associated with age, time since surgery, type of surgery, and radiation therapy in breast cancer patients. The scores serve as a reference value for different types of surgery in the study population and enable prospective use of PROs in shared decision-making.

Nationwide population-based study of trends and regional variation in breast-conserving treatment for breast cancer.

BACKGROUND: Landmark trials have shown breast-conserving surgery (BCS) combined with radiotherapy to be as safe as mastectomy in breast cancer treatment. This population-based study aimed to evaluate trends in BCS from 1989 to 2015 in nine geographical regions in the Netherlands. METHODS: All women diagnosed between 1989 and 2015 with primary T1-2 N0-1 breast cancer, treated with BCS or mastectomy, were identified from the Netherlands Cancer Registry. Crude and case mix-adjusted rates of BCS were evaluated and compared between nine Dutch regions for two time intervals: 1989-2002 and 2003-2015. The annual percentage change in BCS per region over time was assessed by means of Joinpoint regression analyses. Explanatory variables associated with the choice of initial surgery were evaluated using multivariable logistic regression. RESULTS: A total of 202 934 patients were included, 82 200 treated in 1989-2002 and 120 734 in 2003-2015. During 1989-2002, the mean rate of BCS was 50·6 per cent, varying significantly from 39·0 to 71·7 per cent between the nine regions. For most regions, a marked rise in BCS was observed between 2002 and 2003. During 2003-2015, the mean rate of BCS increased to 67·4 per cent, but still varied significantly between regions from 58·5 to 75·5 per cent. A significant variation remained after case-mix correction. CONCLUSION: This large nationwide study showed that the use of BCS increased from 1989 to 2015 in the Netherlands. After adjustment for explanatory variables, a large variation still existed between the nine regions. This regional variation underlines the need for implementation of a uniform treatment and decision-making strategy.

Breast and Tumour Volume Measurements in Breast Cancer Patients Using 3-D Automated Breast Volume Scanner Images.

BACKGROUND: The resection volume in relation to the breast volume is known to influence cosmetic outcome following breast-conserving therapy. It was hypothesised that three-dimensional ultrasonography (3-D US) could be used to preoperatively assess breast and tumour volume and show high association with histopathological measurements. METHODS: Breast volume by the 3D-US was compared to the water displacement method (WDM), mastectomy specimen weight, 3-D MRI and three different calculations for breast volume on mammography. Tumour volume by the 3-D US was compared to the histopathological tumour volume and 3-D MRI. Relatedness was based on the intraclass correlation coefficient (ICC) with corresponding 95% confidence interval (95% CI). Bland-Altman plots were used to graphically display the agreement for the different assessment techniques. All measurements were performed by one observer. RESULTS: A total of 36 patients were included, 20 and 23 for the evaluation of breast and tumour volume (ductal invasive carcinomas), respectively. 3-D US breast volume showed 'excellent' association with WDM, ICC 0.92 [95% CI (0.80-0.97)]. 3-D US tumour volume showed a 'excellent' association with histopathological tumour volume, ICC 0.78 [95% CI (0.55-0.91)]. Bland-Altman plots showed an increased overestimation in lager tumour volumes measured by 3-D MRI compared to histopathological volume. CONCLUSIONS: 3-D US showed a high association with gold standard WDM for the preoperative assessment of breast volume and the histopathological measurement of tumour volume. 3-D US is an patient-friendly preoperative available technique to calculate both breast volume and tumour volume. Volume measurements are promising in outcome prediction of intended breast-conserving treatment.

Prognosis of residual axillary disease after neoadjuvant chemotherapy in clinically node-positive breast cancer patients: isolated tumor cells and micrometastases carry a better prognosis than macrometastases.

PURPOSE: The aim of this study was to compare disease-free survival (DFS) and overall survival (OS) between clinically node-positive breast cancer patients, treated with neoadjuvant chemotherapy (NAC), with axillary pathologic complete response (ypN0), residual axillary isolated tumor cells or micrometastases (ypNitc/mi), and residual axillary macrometastases (ypN1-3). METHODS: All patients diagnosed with clinically node-positive primary invasive breast cancer treated with NAC and subsequent axillary lymph node dissection between 2005 and 2008 were retrospectively analyzed. Data were obtained from the Netherlands Cancer Registry. Patients were stratified by final pathological axillary status: ypN0, ypNitc/mi, or ypN1-3. The main outcome measures DFS and OS were analyzed using Kaplan-Meier survival analysis. Uni- and multivariable cox regression analyses were used to determine independent predictors for DFS and OS. RESULTS: A total of 1347 patients were included. Pathologic nodal status was ypN0 in 22.2%, ypNitc/mi in 3.8%, and ypN1-3 in 74.0% of patients. Overall, 5-year DFS was 57.8% and mean OS was 7.4 years. DFS and OS were comparable between ypN0 and ypNitc/mi (HR 1.38 (0.40-4.79, p = 0.613) and HR 0.92 (0.27-3.09, p = 0.889), respectively), but significantly different between ypN0 and ypN1-3 (HR 1.78 (1.06-3.00, p = 0.031) and HR 1.70 (1.07-2.71, p = 0.026), respectively). CONCLUSIONS: Clinically node-positive patients, treated with NAC, with axillary nodal status ypN0 or ypNitc/mi carry similar prognosis regarding DFS and OS. Axillary nodal status ypN1-3 is associated with a less favorable prognosis. Future studies should consider ypN0 and ypNitc/mi as one entity.

TUmor-volume to breast-volume RAtio for improving COSmetic results in breast cancer patients (TURACOS); a randomized controlled trial.

BACKGROUND: Cosmetic result following breast conserving surgery (BCS) for cancer influences quality of life and psychosocial functioning in breast cancer patients. A preoperative prediction of expected cosmetic result following BCS is not (yet) standard clinical practice and therefore the choice for either mastectomy or BCS is still subjective. Recently, we showed that tumour volume to breast volume ratio as well as tumour location in the breast are independent predictors of superior cosmetic result following BCS. Implementation of a prediction model including both factors, has not been studied in a prospective manner. This study aims to improve cosmetic outcome by implementation of a prediction model in the treatment decision making for breast cancer patients opting for BCS. METHODS/DESIGN: Multicentre, single-blinded, randomized controlled trial comparing standard preoperative work-up to a preoperative work-up with addition of the prediction model. Tumour volume to breast volume ratio and tumour location in the breast will be used to predict cosmetic outcome in invasive breast cancer patients opting for BCS. Three dimensional (3D)-ultrasonography will be used to measure the tumour volume to breast volume ratio needed for the prediction model. Sample size was estimated based on a 14% improvement in incidence of superior cosmetic result one year after BCS (71% in the control group versus 85% in the intervention group). Primarily cosmetic outcome will be evaluated by a 6-member independent panel. Secondary endpoints include; (1) patient reported outcome measured by BREAST-Q, EORTC-QLQ-C30/BR23 and EQ-5D-5 L (2) cosmetic outcome as assessed through the BCCT.core software, (3) radiation-induced reaction (4) surgical treatment performed, (5) pathological result and (6) cost-effectiveness. Follow-up data will be collected for 3 years after surgery or finishing radiotherapy. DISCUSSION: This randomized controlled trial examines the value of a preoperative prediction model for the treatment-decision making. It aims for a superior cosmetic result in breast cancer patients opting for BCS. We expect improvement of patients' quality of life and psychosocial functioning in a cost-effective way. TRIAL REGISTRATION: Prospectively registered, February 17th 2015, at 'Nederlands Trialregister - NTR4997 '.

Benefits of preoperative MRI in breast cancer surgery studied in a large population-based cancer registry.

BACKGROUND: Although evidence for the benefits of preoperative MRI in breast cancer is lacking, use of MRI is increasing and characterized by large interhospital variation. The aim of the study was to evaluate MRI use and surgical outcomes retrospectively. METHODS: Women with invasive breast cancer (pT1-3) or ductal carcinoma in situ (DCIS), diagnosed in 2011-2013, were selected from the Netherlands Cancer Registry and subdivided into the following groups: invasive cancer, high-grade DCIS, non-palpable cancer, age 40 years or less, and invasive lobular cancer. Associations between preoperative MRI use and initial mastectomy, resection margin after breast-conserving surgery (BCS), re-excision after BCS, and final mastectomy were analysed. RESULTS: In total, 5514 women were included in the study; 1637 (34·1 per cent) of 4801 women with invasive cancer and 150 (21·0 per cent) of 713 with DCIS had preoperative MRI. Positive resection margins were found in 18·1 per cent women who had MRI and in 15·1 per cent of those who did not (adjusted odds ratio (OR) 1·20, 95 per cent c.i. 1·00 to 1·45), with no differences in subgroups. Re-excision rates were 9·8 per cent in the MRI group and 7·2 per cent in the no-MRI group (adjusted OR 1·33, 1·04 to 1·70), with no differences in subgroups. In the MRI group, 38·8 per cent of patients ultimately underwent mastectomy, compared with 24·2 per cent in the no-MRI group (adjusted OR 2·13, 1·87 to 2·41). This difference was not found for patients aged 40 years or less, or for those diagnosed with lobular cancer. CONCLUSION: No subgroup was identified in which preoperative MRI influenced the risk of margin involvement or re-excision rate after BCS. MRI was significantly associated with more extensive surgery, except in patients aged 40 years or less and those with invasive lobular cancer. These results suggest that use of preoperative MRI should be more targeted, and that general, widespread use be discouraged.

Self-perceived cognitive impairment in the first year after breast cancer and the identification of at-risk patients.

PURPOSE: This study investigated self-reported clinically relevant cognitive impairment of breast cancer patients in routine clinical care and assessed factors associated with new-onset clinically relevant cognitive impairment. METHODS: Cognitive functioning was assessed before start of any treatment (T0) and at 6 (T6) and 12 (T12) months after diagnosis. Cognitive functioning (CF) was measured on a scale of 0-100 with the EORTC QLQ-C30 questionnaire, and the EORTC pre-defined threshold for clinical importance. Multivariable logistic regression analyses was used to identify factors associated with new-onset clinically relevant cognitive impairment at T6 ((CF > 75 at T0 and CF < 75 at T6 and T12) or (CF > 75 at T0 and T6 and <75 at T12)). RESULTS: Pre-treatment, 21% of patients reported clinically relevant cognitive impairment. At T12, percentage was 32%; 20% of patients reported new-onset clinically relevant cognitive impairment at T6 and/or T12. New-onset clinically relevant cognitive impairment was associated with chemo(immuno)therapy and impairment in role and emotional functioning. Younger patients and patients receiving chemo(immuno)therapy were more likely to report new-onset clinically relevant cognitive impairment post treatment. CONCLUSION: One in five breast cancer patients reported clinically relevant cognitive problems before start of treatment. This percentage further increased within the first year, particularly among patients treated with chemo(immuno)therapy. One in five patients reported new-onset clinically relevant cognitive impairment. Ultimately, these patients may benefit from systematic monitoring and potential referral to interventions.

Seizing the moment: The time for harnessing electronic patient-reported outcome measures for enhanced and sustainable metastatic breast cancer care is now.

The sustainability of healthcare systems is under pressure. Unlike care for many other chronic diseases, cancer care has yet to empower patients in effectively self-managing both the medical and emotional consequences of their condition, including adapting to changes in lifestyle and work, which is essential to achieve optimal health and recovery. Although proposed as a potential solution for sustainable healthcare and support for optimal health and recovery already decades ago, practical implementation of digital care lags behind. We believe electronic patient reported outcome measures (ePROMs) could play an important role in creating sustainable healthcare, both to guide complex treatment pathways and to empower survivors to self-manage consequences of diagnosis and treatment. That is, ePROMs can be used for screening and monitoring of symptoms, but also for treatment decision-making and to facilitate communication about quality of life. We therefore see opportunities for improvements in quality of care, quality of life, and survival of cancer patients, as well as research opportunities, as ePROMs collection can lead to better understanding of care needs. The '10 Actions for Change report' of the Advanced Breast Cancer Global Alliance stresses a critical need for improvement of care for metastatic breast cancer (MBC) patients. We therefore in this paper focus on MBC care and research.

Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: a prospective analysis.

BACKGROUND: To prospectively assess the efficacy of bilateral risk-reducing mastectomy (BRRM) when compared with surveillance on breast cancer (BC) risk and mortality in healthy BRCA1 and BRCA2 mutation carriers. PATIENTS AND METHODS: Five hundred and seventy healthy female mutation carriers (405 BRCA1, 165 BRCA2) were selected from the institutional Family Cancer Clinic database. Eventually, 156 BRCA1 and 56 BRCA2 mutation carriers underwent BRRM. The effect of BRRM versus surveillance was estimated using Cox models. RESULTS: During 2037 person-years of observation (PYO), 57 BC cases occurred in the surveillance group versus zero cases during 1379 PYO in the BRRM group (incidence rates, 28 and 0 per 1000 PYO, respectively). In the surveillance group, four women died of BC, while one woman in the BRRM group presented with metastatic BC 3.5 years after BRRM (no primary BC), and died afterward, yielding a HR of 0.29 (95% CI 0.02-2.61) for BC-specific mortality. CONCLUSIONS: In healthy BRCA1/2 mutation carriers, BRRM when compared with surveillance reduces BC risk substantially, while longer follow-up is warranted to confirm survival benefits.

Impact of age and co-morbidity on surgical resection rate and survival in patients with oesophageal and gastric cancer.

BACKGROUND: Major surgery for cancer has become safer, including for elderly patients with co-morbidity. The aim of this study was to investigate the association between patient characteristics, resection rates and survival among patients with oesophageal or gastric cancer. METHODS: The prospective Dutch population-based Eindhoven Cancer Registry for oesophagogastric cancers diagnosed between 1995 and 2009 was studied retrospectively for patient characteristics including co-morbidity. Logistic regression analysis was performed to assess the likelihood of resection in patients with tumour node metastasis (TNM) stage I-III lesions. Cox proportional hazard analysis was used to estimate hazard ratios (HRs) for survival. RESULTS: The database contained information on 923 patients with oesophageal squamous cell carcinoma, 1181 with distal oesophageal, 942 with cardia and 3177 with subcardia cancer. Of patients with TNM stage I-III disease, 20·8 per cent (557 of 2680 patients) did not undergo resection. Age 70 years or above was associated with a lower likelihood of resection for distal oesophageal (odds ratio (OR) 0·24, 95 per cent confidence interval (c.i.) 0·14 to 0·41) and gastric (cardia: OR 0·41, 0·22 to 0·76; subcardia: OR 0·68, 0·48 to 0·97) cancer. The 30-day mortality rate increased with age (4·7 per cent in patients aged less than 70 years versus 11·9 per cent in those aged 70 years or more; P < 0·001) and co-morbidity (no co-morbidity, 3·6 per cent; 1 co-morbidity, 8·6 per cent; 2 or more co-morbidities, 11·2 per cent; P = 0·015). Surgery (compared with no surgery) was independently associated with better survival for all tumour types. After adjustment for treatment differences, age 70 years or above and presence of two or more co-morbidities were independently associated with poorer survival, especially in patients with subcardia carcinoma (age 70 years or more: HR 1·27, 95 per cent c.i. 1·17 to 1·48; co-morbidity: HR 1·33, 1·21 to 1·62). CONCLUSION: Surgical compared with non-surgical treatment of oesophagogastric cancer was associated with better survival, but postoperative mortality was increased in patients of advanced age and with greater co-morbidity.

Predictors of delayed breast reconstruction in the Netherlands: a 5-year follow-up study in stage I-III breast cancer patients.

PURPOSE: Delayed breast reconstruction (DBR) is a valid option for postmastectomy breast cancer patients who have a desire for breast reconstruction but are not considered suitable for immediate breast reconstruction (IBR). The objective of this study was to investigate the clinical practice and predictors of the use of DBR in the Netherlands. METHODS: Stage I-III breast cancer patients diagnosed from January to March 2012 and treated with mastectomy were selected from the Netherlands Cancer Registry. Routinely collected patient, tumor, treatment and hospital characteristics were complemented with data about DBR up to 2018. Multivariable logistic regression analyses were performed to identify factors independently associated with postmastectomy DBR. Factors associated with time to DBR were identified through Cox regression analyses. RESULTS: Of all patients who underwent mastectomy (n = 1,415), 10.2% underwent DBR. DBR patients more often received autologous reconstruction compared to IBR patients (37.5% vs 6.2%, p < 0.001). Age below 50 years (age < 35 OR 15.55, age 35-49 OR 4.18) and neoadjuvant and adjuvant chemotherapy (OR 2.59 and OR 2.83, respectively) were significantly associated with DBR. Mean time to DBR was 2.4 years [range 1-6 years]. Time to DBR was significantly associated with age < 35 years (HR 2.22), and a high hospital volume (HR 1.87). DISCUSSION: The use of DBR after mastectomy could not be fully explained by age below 50 years, chemotherapy, and hospital volume. Treatment with radiotherapy and adjuvant chemotherapy increased time to DBR. More information about patient preferences is needed to understand the use and timing of reconstruction.

Patient-Reported Outcome Measures may optimize shared decision-making for cancer risk management in BRCA mutation carriers.

PURPOSE: The aim of this study was to compare patient-reported outcomes (PROs) of BRCA1/2 mutation carriers, either after bilateral prophylactic mastectomy (BPM) or during breast surveillance, to improve shared decision-making in their cancer risk management. METHODS: Unaffected BRCA1/2 mutation carriers at least one year after BPM followed by immediate breast reconstruction (BPM-IBR) or one year under surveillance were eligible. After informed consent, the Hospital Anxiety and Depression Scale (HADS) and BREAST-Q were administered and compared between the different strategies. PROs were also compared to available normative data. RESULTS: Ninety-six participants were analyzed in this study and showed significant differences between strategies in age, age at genetic testing, and time since BPM or starting breast surveillance. All HADS scores were below 8 suggesting no signs of anxiety or depression in both groups. Higher mean 'Q-physical well-being' scores were reported by the surveillance group (81.78 [CI 76.99-86.57]) than the BPM group (76.96 [CI 73.16 - 80.75]; p = 0.011). Overall, for both questionnaires better scores were seen when compared to age-matched normative data. CONCLUSIONS: No signs of anxiety or depression were seen in the surveillance or BPM-IBR group. Slightly better mean BREAST-Q scores were seen for the surveillance group in comparison to BPM-IBR, except for 'Q-psychological well-being'. The difference in 'Q-physical well-being' was significantly worse for BPM-IBR. Approaches to obtain longitudinal PROs and reference values should be explored in the future, which could add value to shared decision-making in regards to breast cancer risk management in this specific patient population.

Patterns of axillary staging and management in clinically node positive breast cancer patients treated with neoadjuvant systemic therapy: Results of a survey amongst breast cancer specialists.

INTRODUCTION: Various options for axillary staging after neoadjuvant systemic therapy (NST) are available for breast cancer patients with a clinically positive axillary node (cN+). This survey assessed current practices amongst breast cancer specialists. MATERIALS AND METHODS: A survey was performed amongst members of the European Society of Surgical Oncology and two UK-based Associations: the Association of Breast Surgery and the British Association of Surgical Oncology. The survey included 3 parts: 1. general information, 2. diagnostic work-up and 3. axillary staging after NST. RESULTS: A total of 310 responses were collected: parts 1, 2 and 3 were fully completed by 282 (91%), 270 (87.1%) and 225 (72.6%) respondents respectively. After NST, 153/267 (57.3%) respondents currently perform ALND routinely and 114 (42.7%) respondents perform less invasive restaging of the axilla with possible omission of ALND. In the latter group, 85% does and 15% does not use nodal response seen on imaging to guide the axillary restaging procedure. Regarding respondents that do use imaging: 95% would perform a less invasive staging procedure in case of complete nodal response on imaging (63% sentinel lymph node biopsy (SLNB), excision of a previously marked positive node with SLNB (21%) and without SLNB (11%)). In case of no nodal response on imaging 77% would perform ALND. CONCLUSION: Current axillary staging and management practices in cN + patients after NST vary widely. To determine optimal axillary staging and management in terms of quality of life and oncologic safety, breast specialists are encouraged to include patients in clinical trials/prospective registries.

Chemotherapy followed by surgery in patients with carcinoma of the distal esophagus and celiac lymph node involvement.

BACKGROUND: Patients with carcinoma of the distal esophagus and metastatic celiac lymph nodes (M1a) have a poor prognosis and are often denied surgery. In this study, we evaluated our treatment strategy of chemotherapy followed by surgery in patients with M1a disease. METHODS: Thirty-eight patients who received chemotherapy for carcinoma of the distal esophagus with celiac lymph node involvement between 2000 and 2007 were identified from a prospective database. Clinical and histopathological responses to chemotherapy were analyzed and follow-up comprised review of medical charts. RESULTS: Twelve non-responding patients were not eligible for surgery. Twenty-six patients with partial responses or stable disease were operated on. The resectability rate was 96% (25/26) and tumor-free resection margins (R0) were achieved in 68% (17/25). The overall survival of patients with M1a disease was 16 months. Patients who received chemotherapy alone had a median survival of 10 months; patients who underwent additional surgery had a median survival of 26 months (log-rank P < 0.001). CONCLUSION: The overall survival of patients with carcinoma of the distal esophagus and clinical celiac lymph node involvement is poor. Tumor-free resection margins (R0) in M1a patients with clinical response to chemotherapy are likely to be achieved and contributes to prolonged survival.

Implementation of Value Based Breast Cancer Care.

PURPOSE: Adding value of care to patients is crucial for all stakeholders. The use of both provider and patient reported outcome data was implemented in a single academic breast cancer center. We describe the development of the outcomes set, data integration within electronical health records (EHR) and clinical use. METHODS: An Integrated Practice Unit (IPU) was constructed providing the full care cycle for breast cancer patients. Provider reported outcomes and patient reported outcomes (PROs) were defined, reflecting the entire cycle of care and long-term sustainability of quality of life. Multidisciplinary provider and patient perspectives were obtained via focus groups and surveys. Patient pathways were redesigned in order to identify suitable opportunities for data collection during the entire care cycle. RESULTS: A Standard Set for Breast Cancer Outcomes together with case-mix variables and timelines was agreed upon within the IPU. A secure electronic platform, directly linked to the EHR, was designed to measure PROs during the outpatient phase. First year evaluation showed a decrease of response rates over time, from 83.3% at baseline to 45.2% at 12 months after surgery. Patients reacted positively to the use of PROMs in daily clinical cancer care. CONCLUSION: Assessment of patient reported as well as provider reported outcomes was implemented within our standard of breast cancer care. For this, dedicated resources, change of culture and practice, and improved knowledge and awareness about Value-based healthcare (VBHC) were essential. Our proposed framework aims to serve as a blueprint for implementation of VBHC in daily care.

Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS).

BACKGROUND: A surgical resection is currently the preferred treatment for esophageal cancer if the tumor is considered to be resectable without evidence of distant metastases (cT1-3 N0-1 M0). A high percentage of irradical resections is reported in studies using neoadjuvant chemotherapy followed by surgery versus surgery alone and in trials in which patients are treated with surgery alone. Improvement of locoregional control by using neoadjuvant chemoradiotherapy might therefore improve the prognosis in these patients. We previously reported that after neoadjuvant chemoradiotherapy with weekly administrations of Carboplatin and Paclitaxel combined with concurrent radiotherapy nearly always a complete R0-resection could be performed. The concept that this neoadjuvant chemoradiotherapy regimen improves overall survival has, however, to be proven in a randomized phase III trial. METHODS/DESIGN: The CROSS trial is a multicenter, randomized phase III, clinical trial. The study compares neoadjuvant chemoradiotherapy followed by surgery with surgery alone in patients with potentially curable esophageal cancer, with inclusion of 175 patients per arm.The objectives of the CROSS trial are to compare median survival rates and quality of life (before, during and after treatment), pathological responses, progression free survival, the number of R0 resections, treatment toxicity and costs between patients treated with neoadjuvant chemoradiotherapy followed by surgery with surgery alone for surgically resectable esophageal adenocarcinoma or squamous cell carcinoma. Over a 5 week period concurrent chemoradiotherapy will be applied on an outpatient basis. Paclitaxel (50 mg/m2) and Carboplatin (Area-Under-Curve = 2) are administered by i.v. infusion on days 1, 8, 15, 22, and 29. External beam radiation with a total dose of 41.4 Gy is given in 23 fractions of 1.8 Gy, 5 fractions a week. After completion of the protocol, patients will be followed up every 3 months for the first year, every 6 months for the second year, and then at the end of each year until 5 years after treatment. Quality of life questionnaires will be filled out during the first year of follow-up. DISCUSSION: This study will contribute to the evidence on any benefits of neoadjuvant treatment in esophageal cancer patients using a promising chemoradiotherapy regimen. TRIAL REGISTRATION: ISRCTN80832026.