European Journal of Cancer

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ISSN / EISSN : 0959-8049 / 1879-0852
Published by: Elsevier BV (10.1016)
Total articles ≅ 36,816
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Willeke G. van der Plas-Krijgsman, , Nienke A. de Glas, , , Geoffrey R. Holmes, Susan E. Ward, Tim Chater, , Jos W.S. Merkus, et al.
Published: 23 January 2022
European Journal of Cancer, Volume 163, pp 189-199;

Background Previous studies have shown that survival outcomes for older patients with breast cancer vary substantially across Europe, with worse survival reported in the United Kingdom. It has been hypothesised that these differences in survival outcomes could be related to treatment variation. Objectives We aimed to compare patient and tumour characteristics, treatment selection and survival outcomes between two large prospective cohorts of older patients with operable breast cancer from the United Kingdom (UK) and The Netherlands. Methods Women diagnosed with operable breast cancer aged ≥70 years were included. A baseline comprehensive geriatric assessment was performed in both cohorts, with data collected on age, comorbidities, cognition, nutritional and functional status. Baseline tumour characteristics and treatment type were collected. Univariable and multivariable Cox regression models were used to compare overall survival between the cohorts. Results 3262 patients from the UK Age Gap cohort and 618 patients from the Dutch Climb cohort were included, with median ages of 77.0 (IQR: 72.0–81.0) and 75.0 (IQR: 72.0–81.0) years, respectively. The cohorts were generally comparable, with slight differences in rates of comorbidity and frailty. Median follow-up for overall survival was 4.1 years (IQR 2.9–5.4) in Age Gap and 4.3 years (IQR 2.9–5.5) in Climb. In Age Gap, both the rates of primary endocrine therapy and adjuvant hormonal therapy after surgery were approximately twice those in Climb (16.6% versus 7.3%, p < 0.001 for primary endocrine therapy, and 62.2% versus 38.8%, p < 0.001 for adjuvant hormonal therapy). There was no evidence of a difference in overall survival between the cohorts (adjusted HR 0.94, 95% CI 0.74–1.17, p = 0.568). Conclusions In contrast to previous studies, this comparison of two large national prospective longitudinal multi-centre cohort studies demonstrated comparable survival outcomes between older patients with breast cancer treated in the UK and The Netherlands, despite differences in treatment allocation.
Published: 21 January 2022
European Journal of Cancer, Volume 163, pp 163-176;

Purpose Nearly 50% of patients recur within two years after curatively intended resection of colorectal cancer liver metastasis (CRLM). The optimal surveillance strategy is unknown due to the lack of evidence. Here, we explored the potential for improving postoperative CRLM surveillance by performing serial circulating tumour DNA (ctDNA) assessments parallel to standard-of-care surveillance. Experimental design 499 prospectively collected serial plasma samples from 96 patients undergoing CRLM resection were analysed using the tumour-agnostic methylation multiplex droplet-digital PCR test ‘TriMeth'. Results Patients with ctDNA postoperatively or post adjuvant chemotherapy experienced a significant lower recurrence-free survival than patients without ctDNA (hazard ratio (HR) 4.5; P < 0.0001 and HR 8.4, P< 0.0001). ctDNA status was a stronger predictor of recurrence than standard clinical risk factors and carcinoembryonic antigen. Serial TriMeth analysis detected ctDNA before radiological recurrence in 55.6% of ctDNA-positive patients, with up to 10.6 months lead-time (median 3.1 months). During surveillance, 24% of patients had inconclusive CT scans, which was associated with a significant delay in recurrence diagnosis (median 3.5 months versus 1.0 month, P< 0.0001). Uniquely, ctDNA status at the time of inconclusive CT scans predicted recurrence with positive and negative predictive values of 100%, and 75% (P = 0.0003). Serial TriMeth analysis allowed ctDNA growth rate assessment and revealed that fast ctDNA growth was associated with poor overall survival (HR: 1.6, P = 0.0052). Conclusions Serial postoperative ctDNA analysis has a strong prognostic value and is more sensitive for recurrence detection than standard-of-care CRLM surveillance tools. Altogether, TriMeth provides several opportunities for improving postoperative surveillance of CRLM patients.
, , Sarah Albers, Therese Pross, Anna M. Hage, Karoline Weiler, Felix Fischer, Matthias Rose, ,
Published: 21 January 2022
European Journal of Cancer, Volume 163, pp 128-139;

Purpose To deliver patient-reported outcome (PRO) reference data for breast cancer and various other breast diseases to facilitate the interpretation of PRO scores during routine breast cancer treatment. Methods To determine reference baseline values for the PRO measures EORTC QLQ-C30 and EORTC QLQ-BR23, PRO data captured in the breast cancer centre at Charité – Universitätsmedizin Berlin from 2016 to 2021 were evaluated. As part of the clinical routine, ambulatory patients were asked to answer a digital survey regarding their medical history, current health status and health-related quality of life using the aforementioned questionnaires prior to their doctor's appointment in the outpatient breast clinic. Adjusted linear and variable dispersion beta regression models were used to compare different diagnosis groups. Results A total of 3689 patients were included in the digital PRO program, of which 1478 were eligible for this study; 729 had invasive breast cancer or ductal carcinoma in situ, 270 patients were diagnosed with fibroadenoma and 479 patients had other breast diseases such as cysts, mastopathy or abscesses. Overall, patients with breast cancer reported worse scores in almost all domains except for role functioning, sexual functioning and body image. Compared to previously published reference scores for early breast cancer, the current data show a more pronounced impact on perceived emotional and cognitive functioning. Conclusion The results of this study are of high value for the interpretation of PROs and facilitate their use in clinical practice and clinical trials. The scores indicate an urgent need for psychosocial support prior to treatment.
Ardine M.J. Reedijk, Auke Beishuizen, Jan Willem W. Coebergh, , , Konnie M. Hebeda, Rob Pieters, Jan L.C. Loeffen,
Published: 21 January 2022
European Journal of Cancer, Volume 163, pp 140-151;

Background With epidemiologic analyses of population-based trends in incidence and outcomes, we ascertained progress against non-Hodgkin's lymphoma (NHL) in children and young adolescents in the Netherlands since 1990. Methods Tumour characteristics were extracted from the Netherlands Cancer Registry for patients aged <18 years at diagnosis, between 1990 and 2015. Mortality data for 1980–2016 were derived from Statistics Netherlands. NHL subtypes comprised lymphoblastic lymphoma (LBL), Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL). Time trends in incidence and mortality rates and 5-year overall survival (OS) rates were evaluated by average annual percentage change (AAPC) analyses and parametric survival models, respectively. Results Overall incidence of NHL remained stable at 11 per million person-years (AAPC -0.2%, p = 0.68), with a marked decrease among children of 5–9 years (AAPC -2.6%, p< 0.01), especially among those with BL. Treatment regimens comprised less radiotherapy over time, especially for LBL and BL. Since 2004, most 15–17-year-old patients with NHL have been treated at a paediatric oncology centre. Five-year OS improved from 71% in 1990–94 to 87% in 2010–15 (p< 0.01), the most gain has been achieved in patients with DLBCL and ALCL from 60% and 73%, respectively, to both 90%. Population-based mortality from NHL decreased significantly towards 1.4 per million person-years (AAPC -4.2%, p< 0.01). Conclusions This population-based epidemiological study exhibited significant progress against childhood and young adolescent NHL in the Netherlands since 1990, before the advent of a national paediatric oncologic centre in 2018: incidence decreased among children of 5–9 years, survival improved, and mortality steadily decreased over time.
Zhan Wang, Bao-Dong Qin, Chen-Yang Ye, Miao-Miao Wang, Ling-Yan Yuan, Wei-Ping Dai, Li Sun, Ke Liu, Wen-Xing Qin, Xiao-Dong Jiao, et al.
Published: 21 January 2022
European Journal of Cancer, Volume 163, pp 152-162;

The publisher has not yet granted permission to display this abstract.
Joo-Hyun Park, Kyungdo Han, , Young Suk Park,
Published: 19 January 2022
European Journal of Cancer, Volume 163, pp 119-127;

The publisher has not yet granted permission to display this abstract.
, Olivier Michielin, Thiago Quinaglia, Daniel A. Zlotoff, Leyre Zubiri, Hannah K. Gilman, Sama Supraja, Bela Merkely, , , et al.
Published: 19 January 2022
European Journal of Cancer, Volume 163, pp 108-118;

Background Preclinical studies indicate that the concurrent use of inhibitors of the renin–angiotensin–aldosterone system (RAAS) may improve outcomes in broad groups of patients with cancer. There are limited data on the association between the use of RAAS inhibitors and outcomes among patients treated with immune checkpoint inhibitors (ICIs). Methods We performed a retrospective study of all patients treated with an ICI in a single academic network. Of 10,903 patients, 5910 were on any anti-hypertensive medication. Of those on anti-hypertensive therapy, 3426 were prescribed a RAAS inhibitor during ICI treatment, and 2484 were prescribed other anti-hypertensive medications. The primary outcome was overall survival in the entire cohort and in sub-groups by cancer types. Results Thoracic cancer (34%) and melanoma (16%) were the most common types of cancer. Those prescribed a RAAS inhibitor were older, more frequently male, and had more cardiovascular risk factors. In a Cox proportional hazard model, the concurrent use of RAAS inhibitors was associated with better overall survival (hazard ratio (HR):0.92, [95% Confidence Interval (CI):0.85–0.99], P = .032). Patients with gastrointestinal (HR:0.82, [95% CI: 0.67–1.01], P = .057) and genitourinary cancer (HR:0.81, [95% CI:0.64–1.01], P = .067) had a non-statistically significant better overall survival. Conclusions In this large retrospective study, patients with hypertension who were concomitantly taking a RAAS inhibitor during ICI therapy had better overall survival. This benefit was primarily noted among patients with gastrointestinal and genitourinary cancers. Prospective randomized trials are warranted to further evaluate and specify the benefit of RAAS inhibitors in patients with cancer who receive ICI therapy.
, Nadia Younan, Eduardo Castanon Alvarez, Samy Ammari, Agusti Alentorn, Sarah Dumont, Jean-Sebastien Frenel, Anna-Luisa Di Stefano, Guillaume Louvel, Jean-Marie Michot, et al.
Published: 18 January 2022
European Journal of Cancer, Volume 163, pp 98-107;

The publisher has not yet granted permission to display this abstract.
, Harm van Tinteren, Yilin Jiang, Ronald R. de Krijger, Gordan M. Vujanic, Jan Godzinski, Christian Rübe, Jens-Peter Schenk, Carlo Morosi, Kathy Pritchard-Jones, et al.
Published: 15 January 2022
European Journal of Cancer, Volume 163, pp 88-97;

Purpose Society of International Pediatric Oncology – Renal Tumor Study Group (SIOP-RTSG) treatment recommendations for relapsed Wilms tumour (WT) are stratified by the intensity of first-line treatment. To explore the evidence for the treatment of patients relapsing after vincristine and actinomycin-D (VA) treatment for primary WT, we retrospectively evaluated rescue treatment and survival of this patient group. Patients and methods We included 109 patients with relapse after VA therapy (no radiotherapy) for stage I-II primary low- or intermediate-risk WT from the SIOP 93–01 and SIOP 2001 studies. Univariate Cox regression analysis was performed to study the effect of relapse treatment intensity on event-free survival (EFS) and overall survival (OS). Relapse treatment intensity was classified into vincristine, actinomycin-D, and either doxorubicin or epirubicin (VAD), and more intensive therapies (ifosfamide/carboplatin/etoposide [ICE]/≥ 4 drugs/high-dose chemotherapy with haematopoietic stem cell transplantation [HD HSCT]). Results Relapse treatment regimens included either VAD, or cyclophosphamide/carboplatin/etoposide/doxorubicin (CyCED), or ICE backbones. Radiotherapy was administered in 62 patients and HD HSCT in 15 patients. Overall, 5-year EFS and OS after relapse were 72.3% (95% confidence interval [CI]: 64.0–81.6%) and 79.3% (95% CI: 71.5–88.0%), respectively. Patients treated with VAD did not fare worse when compared with patients treated with more intensive therapies (hazard ratio EFS: 0.611 [95% CI: 0.228–1.638] [p-value = 0.327] and hazard ratio OS: 0.438 [95% CI: 0.126–1.700] [p-value = 0.193]). Conclusion Patients with relapsed WT after initial VA-only treatment showed no inferior EFS and OS when treated with VAD regimens compared with more intensive rescue regimens. A subset of patients relapsing after VA may benefit from less intensive rescue treatment than ICE/CyCED-based regimens and deserve to be pinpointed by identifying additional (molecular) prognostic factors in future studies.
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