Effect of neoadjuvant chemoradiotherapy on health-Related quality of life in esophageal or junctional cancer: Results from the randomized CROSS trial

Purpose To compare pre-agreed health-related quality of life (HRQOL) domains in patients with esophageal or junctional cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery or surgery alone. Secondary aims were to examine the effect of nCRT on HRQOL before surgery and the effect of surgery on HRQOL. Patients and Methods Patients were randomly assigned to nCRT (carboplatin plus paclitaxel with concurrent 41.4-Gy radiotherapy) followed by surgery or surgery alone. HRQOL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30) and –Oesophageal Cancer Module (QLQ-OES24) questionnaires pretreatment and at 3, 6, 9, and 12 months postoperatively. The nCRT group also received preoperative questionnaires. Physical functioning (PF; QLQ-C30) and eating problems (EA; QLQ-OES24) were chosen as predefined primary end points. Predefined secondary end points were global QOL (GQOL; QLQ-C30), fatigue (FA; QLQ-C30), and emotional problems (EM; QLQ-OES24). Results A total of 363 patients were analyzed. No statistically significant differences in postoperative HRQOL were found between treatment groups. In the nCRT group, PF, EA, GQOL, FA, and EM scores deteriorated 1 week after nCRT (Cohen’s d: 20.93, P, .001; 0.47, P, .001; 20.84, P, .001; 1.45, P, .001; and 0.32, P = .001, respectively). In both treatment groups, all end points declined 3 months postoperatively compared with baseline (Cohen’s d: 21.00, 0.33, 20.47, 20.34, and 0.33, respectively; all P, .001), followed by a continuous gradual improvement. EA, GQOL, and EM were restored to baseline levels during follow-up, whereas PF and FA remained impaired 1 year postoperatively (Cohen’s d: 0.52 and 20.53, respectively; both P, .001). Conclusion Although HRQOL declined during nCRT, no effect of nCRT was apparent on postoperative HRQOL compared with surgery alone. In addition to the improvement in survival, these findings support the view that nCRT according to the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study–regimen can be regarded as a standard of care

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: A stepped-wedge cluster randomised trial

Background: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods: This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion: If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care

Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial

Contains fulltext : 217596.pdf (Publisher’s version ) (Open Access

Trends and variation in the use of radiotherapy in non-metastatic prostate cancer: a 12-year nationwide overview from The Netherlands

Purpose: This population-based study describes nationwide trends and variation in the use of primary radiotherapy for non-metastatic prostate cancer in The Netherlands in 2008-2019. Methods: Prostate cancer patients were selected from the Netherlands Cancer Registry (N=103,059). Treatment trends were studied over time by prognostic risk groups. Multilevel analyses were applied to identify variables associated with external beam radiotherapy (EBRT) and brachy-monotherapy versus no active treatment in low-risk disease, and EBRT versus radical prostatectomy in intermediate and high-risk disease. Results: EBRT use remained stable (5-6%) in low-risk prostate cancer and increased from 21% to 32% in intermediate-risk, 37% to 45% in high-risk localized and 50% to 57% in high-risk locally advanced disease. Brachy-monotherapy decreased from 19% to 6% and from 15% to 10% in low and intermediate-risk disease, respectively, coinciding an increase of no active treatment from 55% to 73% in low-risk disease. Use of EBRT or brachy-monotherapy versus no active treatment in low-risk disease differed by region, T-stage and patient characteristics. Hospital characteristics were not associated with treatment in low-risk disease, except for availability of brachy-monotherapy in 2008-2013. Age, number of comorbidities, travel time for EBRT, prognostic risk group, and hospital characteristics were associated with EBRT versus prostatectomy in intermediate and high-risk disease. Conclusion: Intermediate/high-risk PCa was increasingly managed with EBRT, while brachy-monotherapy in low/intermediate-risk PCa decreased. In low-risk PCa, the no active treatment-approach increased. Variation in treatment suggests treatment decision related to patient/disease characteristics. In intermediate/high-risk disease, variation seems furthermore related to the treatment modalities available in the diagnosing hospitals

Rate and predictors of nodal pathological complete response following neoadjuvant endocrine treatment in clinically biopsy-proven node-positive breast cancer patients

Background: Data on effectiveness and optimal use of neoadjuvant endocrine therapy (NET) in clinically biopsy-proven node-positive breast cancer is lacking. This study examined the incidence of axillary pathological complete response (pCR) on NET in clinically biopsy-proven node-positive breast cancer patients. Secondary, patient and tumour characteristics, as well as the optimal duration of NET in relation to the occurrence of axillary pCR were investigated. Material and methods: Patients diagnosed with primary hormone receptor positive, HER2 negative breast cancer between 2014 and 2019, with at least one positive axillary lymph node (pathologically proven), treated with NET were selected from the Netherlands Cancer Registry. The incidence of axillary pCR in combination with patient, tumour and treatment characteristics was analysed. Results: In a population of 561 patients, an axillary pCR of 7.3% on NET was observed. Median length of treatment was 8.1 months in the patients without vs. 8.8 months in those with axillary pCR, with no statistically significant difference. A p-value <0.30 was found for age, histologic type, clinical tumour status, hormone receptor status and the type of NET in univariable analysis. After multivariable logistic regression analyses, none of these variables were independently associated with the likelihood of an axillary pCR. Conclusion: The rate of axillary pCR after NET in HR + HER2-clinically biopsy-proven node-positive breast cancer patients is low. Factors independently associated with the likelihood of an axillary pCR could not be identified. More research is warranted regarding optimizing the duration of NET and the prognostic value of residual disease in the axilla after NET

Extended adjuvant aromatase inhibition after sequential endocrine therapy in postmenopausal women with breast cancer:follow-up analysis of the randomised phase 3 DATA trial

Background: The DATA study evaluated the use of two different durations of anastrozole in patients with hormone receptor-positive breast cancer who were disease-free after 2–3 years of tamoxifen. We hereby present the follow-up analysis, which was performed after all patients reached a minimum follow-up of 10 years beyond treatment divergence. Methods: The open-label, randomised, phase 3 DATA study was performed in 79 hospitals in the Netherlands (ClinicalTrials.gov, number NCT00301457). Postmenopausal women with hormone receptor-positive breast cancer who were disease-free after 2–3 years of adjuvant tamoxifen treatment were assigned to either 3 or 6 years of anastrozole (1 mg orally once a day). Randomisation (1:1) was stratified by hormone receptor status, nodal status, HER2 status, and prior tamoxifen duration. The primary outcome was adapted disease-free survival, defined as disease-free survival from 3 years after randomisation onwards. Adapted overall survival was assessed as a secondary outcome. Analyses were performed according to the intention-to-treat design. Findings: Between June 28, 2006, and August 10, 2009, 1912 patients were randomly assigned to 3 years (n = 955) or 6 years (n = 957) of anastrozole. Of these, 1660 patients were eligible and disease-free at 3 years after randomisation. The 10-year adapted disease-free survival was 69.2% (95% CI 55.8–72.3) in the 6-year group (n = 827) and 66.0% (95% CI 62.5–69.2) in the 3-year group (n = 833) (hazard ratio (HR) 0.86; 95% CI 0.72–1.01; p = 0.073). The 10-year adapted overall survival was 80.9% (95% CI 77.9–83.5) in the 6-year group and 79.2% (95% CI 76.2–81.9) in the 3-year group (HR 0.93; 95% CI 0.75–1.16; p = 0.53). Interpretation: Extended aromatase inhibition beyond 5 years of sequential endocrine therapy did not improve the adapted disease-free survival and adapted overall survival of postmenopausal women with hormone receptor-positive breast cancer. Funding: AstraZeneca

Updated protocol of the SANO trial: a stepped-wedge cluster randomised trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancer

Background: The Surgery As Needed for Oesophageal cancer (SANO) trial compares active surveillance with standard oesophagectomy for patients with a clinically complete response (cCR) to neoadjuvant chemoradiotherapy. The last patient with a clinically complete response is expected to be included in May 2021. The purpose of this update is to present all amendments to the SANO trial protocol as approved by the Institutional Research Board (IRB) before accrual is completed. Design: The SANO trial protocol has been published (https://doi.org/10.1186/s12885-018-4034-1). In this ongoing, phase-III, non-inferiority, stepped-wedge, cluster randomised controlled trial, patients with cCR (i.e. after neoadjuvant chemoradiotherapy no evidence of residual disease in two consecutive clinical response evaluations [CREs]) undergo either active surveillance or standard oesophagectomy. In the active surveillance arm, CREs are repeated every 3 months in the first year, every 4 months in the second year, every 6 months in the third year, and yearly in the fourth and fifth year. In this arm, oesophagectomy is offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant metastases. The primary endpoint is overall survival. Update: Amendments to the study design involve the first cluster in the stepped-wedge design being partially randomised as well and continued accrual of patients at baseline until the predetermined number of patients with cCR is reached. Eligibility criteria have been amended, stating that patients who underwent endoscopic treatment prior to neoadjuvant chemoradiotherapy cannot be included and that patients who have highly suspected residual tumour without histological proof can be included. Amendments to the study procedures include that patients proceed to the second CRE if at the first CRE the outcome of the pathological assessment is uncertain and that patients with a non-passable stenosis at endoscopy are not considered cCR. The sample size was recalculated following new insights on response rates (34% instead of 50%) and survival (expected 2-year overall survival of 75% calculated from the moment of reaching cCR instead of 3-year overall survival of 67% calculated from diagnosis). This reduced the number of required patients with cCR from 264 to 224, but increased the required inclusions from 480 to approximately 740 patients at baseline. Conclusion: Substantial amendments were made prior to closure of enrolment of the SANO trial. These amendments do not affect the outcomes of the trial compared to the original protocol. The first results are expected late 2023. If active surveillance plus surgery as needed after neoadjuvant chemoradiotherapy for oesophageal cancer leads to non-inferior overall survival compared to standard oesophagectomy, active surveillance can be implemented as a standard of care

Factors contributing to improved local control after mastectomy in patients with breast cancer aged 40 years or younger.

Item does not contain fulltextLong-term local control rates were studied in a series of 659 patients with invasive breast cancer aged 40 years or younger, who underwent mastectomy in general hospitals in the southern part of the Netherlands between 1988 and 2005. During a median follow-up time of 6.0 years, 34 patients developed a local recurrence in the chest wall without previous or simultaneous evidence of distant disease. The 5- and 10-year actuarial local recurrence rates for the total group were 5.6% (95% confidence interval [95% CI], 3.5-7.7%) and 7.3% (95% CI, 4.7-9.9%), respectively. A multivariate analysis showed that patients receiving radiotherapy (hazards ratio [HR], 0.29; 95% CI, 0.10-0.96) or adjuvant systemic treatment (HR 0.23; 95% CI, 0.08-0.65) had a significantly lower risk of local recurrence. It is concluded that excellent local control rates can be obtained with mastectomy in young women with breast cancer, especially in those who receive adjuvant systemic treatment and/or radiotherapy.1 februari 201

Updated protocol of the SANO trial

Background: The Surgery As Needed for Oesophageal cancer (SANO) trial compares active surveillance with standard oesophagectomy for patients with a clinically complete response (cCR) to neoadjuvant chemoradiotherapy. The last patient with a clinically complete response is expected to be included in May 2021. The purpose of this update is to present all amendments to the SANO trial protocol as approved by the Institutional Research Board (IRB) before accrual is completed. Design: The SANO trial protocol has been published (https://doi.org/10.1186/s12885-018-4034-1). In this ongoing, phase-III, non-inferiority, stepped-wedge, cluster randomised controlled trial, patients with cCR (i.e. after neoadjuvant chemoradiotherapy no evidence of residual disease in two consecutive clinical response evaluations [CREs]) undergo either active surveillance or standard oesophagectomy. In the active surveillance arm, CREs are repeated every 3 months in the first year, every 4 months in the second year, every 6 months in the third year, and yearly in the fourth and fifth year. In this arm, oesophagectomy is offered only to patients in whom locor