| 1. |
|
|
| 2. |
- Bagge, R. Olofsson, et al.
(författare)
-
A phase Ib randomized multicenter trial of isolated hepatic perfusion in combination with ipilimumab and nivolumab for uveal melanoma metastases (SCANDIUM II trial)
- 2024
-
Ingår i: ESMO Open. - : Elsevier. - 2059-7029. ; 9:7
-
Tidskriftsartikel (refereegranskat)abstract
- Background:Uveal melanoma (UM) is a rare malignancy where 50% of patients develop metastatic disease primarily affecting the liver. Approximately 40% of patients with metastatic UM respond to one-time isolated hepatic perfusion (IHP) with high -dose melphalan. This phase I trial investigates the safety and clinical ef fi cacy of IHP combined with ipilimumab (IPI) and nivolumab (NIVO).Patients and methods:Immunotherapy-na & iuml;ve patients were randomized in this phase I trial to receive either IHP followed by IPI 3 mg/kg and NIVO 1 mg/kg (IPI3/NIVO1) for four cycles (post -operative arm), or one cycle of preoperative IPI3/NIVO1, IHP and then three cycles of IPI3/NIVO1 (pre-post-operative arm), followed by maintenance therapy with NIVO 480 mg for 1 year.Results:Eighteen patients were enrolled and randomized. Three patients did not undergo IHP as planned. In total, 11/ 18 patients (6 in the post -operative arm and 5 in the pre-post-operative arm) did not complete the planned four cycles of IPI3/NIVO1. Toxicity to IHP was similar in both groups, but the number of immune-related adverse events (AEs) was higher in the pre-post-operative arm. Among assessable patients, overall response rate was 57% in the post -operative arm (4/7) and 22% in the pre-post-operative arm (2/9).Conclusions:Combination therapy with IHP and IPI3/NIVO1 was associated with severe AEs. The efficacy of this combination is encouraging with high response rates. One cycle of preoperative IPI/NIVO before IHP did not show potential benefits in terms of safety or efficacy.
|
|
| 3. |
- Carlsson, Göran, 1951, et al.
(författare)
-
A phase I/II study of arfolitixorin and 5-fluorouracil in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan in metastatic colorectal cancer
- 2022
-
Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 7:5
-
Tidskriftsartikel (refereegranskat)abstract
- Background: 5-fluorouracil (5-FU) combined with a folate remains an essential treatment component for metastatic colorectal cancer (mCRC). Leucovorin is the folate most often used, but requires intracellular conversion to a reduced folate, and has high pharmacokinetic variability and limited bioavailability in patients with low folate pathway gene expression. Arfolitixorin is an immediately active form of folate, [6R]-5,10-methylenetetrahydrofolate ([6R]-MTHF), and may improve outcomes.Patients and methods: This open-label, multicenter, phase I/II study in patients with mCRC (NCT02244632) assessed the tolerability and efficacy of first-or second-line arfolitixorin (30, 60, 120, or 240 mg/m2 intravenous) with 5-FU alone, or in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan, every 14 days. Safety, efficacy, and pharmacokinetics were assessed before and after four cycles (8 weeks) of treatment.Results: In 105 treated patients, investigators reported 583 adverse events (AEs) in 86 patients (81.9%), and 256 AEs (43.9%) were potentially related to arfolitixorin and 5-FU. Dose adjustments were required in 16 patients (15.2%). At 8 weeks, 9 out of 57 patients assessed for efficacy achieved an objective response (15.8%), and all 9 achieved a partial response. Six of these nine patients had received arfolitixorin as a first-line treatment. A further 33 patients (57.9%) achieved stable disease. Pharmacokinetics were assessed in 35 patients. The average tmax was 10 min, and area under the plasma concentrationetime curve from time 0 to 1 h increased linearly between 30 and 240 mg/m2. No accumulation was observed for [6R]-MTHF following repeated administration, and there were no major pharmacokinetic differences between cycle 1 and cycle 4 at any dose.Conclusions: Arfolitixorin is a well-tolerated moderator of 5-FU activity. It is suitable for further investigation in mCRC and has the potential to improve treatment outcomes in patients with low folate pathway gene expression. Arfolitixorin can easily be incorporated into current standard of care, requiring minimal changes to chemotherapy regimens.
|
|
| 4. |
- Chauca Strand, Gabriella, 1995, et al.
(författare)
-
Assessment of the clinical and cost-effectiveness evidence in the reimbursement decisions of new cancer drugs
- 2022
-
Ingår i: ESMO Open. - : Elsevier. - 2059-7029. ; 7:5
-
Tidskriftsartikel (refereegranskat)abstract
- Background: This study aimed to describe the clinical and cost-effectiveness evidence supporting reimbursementdecisions of new cancer drugs and analyze the influence of trial characteristics and the cost per quality-adjusted lifeyears (QALYs) on the likelihood of reimbursement in Sweden.Patients and methods: Data were extracted from all appraisal dossiers for new cancer drugs seeking reimbursement inSweden and claiming added therapeutical value between the years 2010 and 2020. The data were analyzed usingdescriptive statistics, and logistic regression models were also used with the cost per QALY, study design,comparator, and evidence on final outcomes in the clinical trials as predictors of reimbursement.Results: All 60 included appraisals were based on trial evidence that assessed at least one final outcome (overallsurvival [OS] or quality of life [QoL]), although rarely as a primary outcome. Of the appraisals with a final decision(n ¼ 58), 79% were approved for reimbursement. Among the reimbursed drugs, only half had trial evidencedemonstrating improved OS or QoL. Only one drug had trial evidence supporting improvements in both OS andQoL. The average cost per QALY for reimbursed cancer drugs was estimated to be 748 560 SEK (V73 583). A highercost per QALY was found to decrease the likelihood of reimbursement by 9.4% for every 100 000 SEK (V9830)higher cost per QALY (P ¼ 0.03). For cost-effectiveness models without direct evidence of improvements in finaloutcomes, a larger QALY gain was observed compared with those with evidence mainly relying on intermediate andsurrogate outcomes.Conclusions: There are substantial uncertainties in the clinical and cost-effectiveness evidence underlyingreimbursement decisions of new cancer drugs. Decision makers should be cautious of the limited evidence onpatient-centered outcomes and the implications of allocating resources to expensive treatments with uncertainvalue for money.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Dijkstra, E. A., et al.
(författare)
-
The value of post-operative chemotherapy after chemoradiotherapy in patients with high-risk locally advanced rectal cancerdresults from the RAPIDO trial
- 2023
-
Ingår i: ESMO Open. - : ELSEVIER. - 2059-7029. ; 8:2
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pre-operative chemoradiotherapy (CRT) rather than radiotherapy (RT) has resulted in fewer locoregional recurrences (LRRs), but no decrease in distant metastasis (DM) rate for patients with locally advanced rectal cancer (LARC). In many countries, patients receive post-operative chemotherapy (pCT) to improve oncological outcomes. We investigated the value of pCT after pre-operative CRT in the RAPIDO trial.Patients and methods: Patients were randomised between experimental (short-course RT, chemotherapy and surgery) and standard-of-care treatment (CRT, surgery and pCT depending on hospital policy). In this substudy, we compared curatively resected patients from the standard-of-care group who received pCT (pCT+ group) with those who did not (pCT- group). Subsequently, patients from the pCT+ group who received at least 75% of the prescribed chemotherapy cycles (pCT >75% group) were compared with patients who did not receive pCT (pCT-/- group). By propensity score stratification (PSS), we adjusted for the following unbalanced confounders: age, clinical extramural vascular invasion, distance to the anal verge, ypT stage, ypN stage, residual tumour, serious adverse event (SAE) and/or readmission within 6 weeks after surgery and SAE related to pre-operative CRT. Cumulative probability of disease-free survival (DFS), DM, LRR and overall survival (OS) was analysed by Cox regression.Results: In total, 396/452 patients had a curative resection. The number of patients in the pCT+, pCT >75%, pCT- and pCT-/- groups was 184, 112, 154 and 149, respectively. The PSS-adjusted analyses for all endpoints demonstrated hazard ratios between approximately 0.7 and 0.8 (pCT+ versus pCT-), and 0.5 and 0.8 (pCT >75% versus pCT-/-). However, all 95% confidence intervals included 1.Conclusions: These data suggest a benefit of pCT after pre-operative CRT for patients with high-risk LARC, with approximately 20%-25% improvement in DFS and OS and 20%-25% risk reductions in DM and LRR. Compliance with pCT additionally reduces or improves all endpoints by 10%-20%. However, differences are not statistically significant.
|
|
| 9. |
- Dittrich, Christian, et al.
(författare)
-
ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016
- 2016
-
Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 1:5
-
Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ ASCO Global Curriculum (GC) thanks to contribution of 64 ESMOappointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
|
|
| 10. |
|
|
| 11. |
- Eriksson, Mikael, et al.
(författare)
-
Benefit of pazopanib in advanced gastrointestinal stromal tumours: results from a phase II trial (SSG XXI, PAGIST)
- 2021
-
Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:4
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with advanced gastrointestinal stromal tumours (GISTs) resistant to the tyrosine kinase inhibitors imatinib and sunitinib may be treated with regorafenib, which resulted in a median progression-free survival (PFS) of 4.8 months in the GRID trial. Also, pazopanib, another tyrosine kinase inhibitor, has been studied in a randomized, placebo-controlled trial (PAZOGIST) in the third line, which showed a PFS of 45.2% 4 months after study entry, but patients intolerant to sunitinib were also included. We designed another trial evaluating pazopanib, enrolling only patients with progression on both imatinib and sunitinib. PATIENTS AND METHODS: Since all eligible patients had progressive disease, we preferred a non-randomized, phase II multicentre trial so that all patients could receive a potentially active drug. Patients had a progressive metastatic or locally advanced GIST and were ≥18 years of age, with a performance status of 0-2, and sufficient organ functions. The primary endpoint was disease control rate (defined as complete remission + partial remission + stable disease) at 12 weeks on pazopanib. A Simon's two-stage analysis was used with an interim analysis 12 weeks after enrollment of the first 22 patients, and if passed, there was a full enrolment of 72 patients. GIST mutational analysis was done, and most patients had pazopanib plasma concentration measured after 12 weeks. RESULTS: Seventy-two patients were enrolled. The disease control rate after 12 weeks was 44%, and the median PFS was 19.6 weeks (95% confidence interval 12.6-23.4 weeks). Pazopanib-related toxicity was moderate and manageable. No statistically significant differences were found related to mutations. Plasma concentrations of pazopanib had a formal but weak correlation with outcome. CONCLUSION: Pazopanib given in the third line to patients with GIST progressing on both imatinib and sunitinib was beneficial for about half of the patients. The PAGIST trial confirms the results from the PAZOGIST trial, and the median PFS achieved seems comparable to the PFS achieved with regorafenib in the third-line setting.
|
|
| 12. |
- Ferrari, A., et al.
(författare)
-
Adolescents and young adults (AYA) with cancer : a position paper from the AYA Working Group of the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE)
- 2021
-
Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:2
-
Forskningsöversikt (refereegranskat)abstract
- It is well recognised that adolescents and young adults (AYA) with cancer have inequitable access to oncology services that provide expert cancer care and consider their unique needs. Subsequently, survival gains in this patient population have improved only modestly compared with older adults and children with cancer. In 2015, the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE) established the joint Cancer in AYA Working Group in order to increase awareness among adult and paediatric oncology communities, enhance knowledge on specific issues in AYA and ultimately improve the standard of care for AYA with cancer across Europe. This manuscript reflects the position of this working group regarding current AYA cancer care, the challenges to be addressed and possible solutions. Key challenges include the lack of specific biological understanding of AYA cancers, the lack of access to specialised centres with age-appropriate multidisciplinary care and the lack of available clinical trials with novel therapeutics. Key recommendations include diversifying interprofessional cooperation in AYA care and specific measures to improve trial accrual, including centralising care where that is the best means to achieve trial accrual. This defines a common vision that can lead to improved outcomes for AYA with cancer in Europe.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Hindi, N., et al.
(författare)
-
Efficacy of immune checkpoint inhibitors in alveolar soft-part sarcoma : results from a retrospective worldwide registry
- 2023
-
Ingår i: ESMO Open. - 2059-7029. ; 8:6
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Conventional cytotoxic drugs are not effective in alveolar soft-part sarcoma (ASPS). Immune checkpoint (programmed cell death protein 1/programmed death-ligand 1) inhibitors (ICIs) are promising drugs in ASPS. A worldwide registry explored the efficacy of ICI in ASPS. Materials and methods: Data from adult patients diagnosed with ASPS and treated with ICI for advanced disease in expert sarcoma centers from Europe, Australia and North America were retrospectively collected, including demographics and data related to treatments and outcome. Results: Seventy-six ASPS patients, with a median age at diagnosis of 25 years (range 3-61 years), were registered. All patients received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 38 patients (50%) and combination in 38 (50%) (23 with a tyrosine kinase inhibitor). Among the 68 assessable patients, there were 3 complete responses and 34 partial responses, translating into an overall response rate of 54.4%. After a median follow-up of 36 months [95% confidence interval (CI) 32-40 months] since the start of immunotherapy, 45 (59%) patients have progressed on ICI, with a median progression-free survival (PFS) of 16.3 months (95% CI 8-25 months). Receiving ICI in first line (P = 0.042) and achieving an objective response (P = 0.043) correlated with a better PFS. Median estimated overall survival (OS) from ICI initiation has not been reached. The 12-month and 24-month OS rates were 94% and 81%, respectively. Conclusions: This registry constitutes the largest available series of ASPS treated with ICI. Our results suggest that the ICI treatment provides long-lasting disease control and prolonged OS in patients with advanced ASPS, an ultra-rare entity with limited active therapeutic options.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Lawler, M., et al.
(författare)
-
The European Cancer Patient's Bill of Rights, update and implementation 2016
- 2016
-
Ingår i: Esmo Open. - : Elsevier BV. - 2059-7029. ; 1:6
-
Tidskriftsartikel (refereegranskat)abstract
- In this implementation phase of the European Cancer Patient's Bill of Rights (BoR), we confirm the following three patient-centred principles that underpin this initiative: 1. The right of every European citizen to receive the most accurate information and to be proactively involved in his/her care. 2. The right of every European citizen to optimal and timely access to a diagnosis and to appropriate specialised care, underpinned by research and innovation. 3. The right of every European citizen to receive care in health systems that ensure the best possible cancer prevention, the earliest possible diagnosis of their cancer, improved outcomes, patient rehabilitation, best quality of life and affordable health care. Agree our high-level goal. The vision of 70% longterm survival for patients with cancer in 2035, promoting cancer prevention and cancer control and the associated progress in ensuring good patient experience and quality of life. Establish the major mechanisms to underpin its delivery. (1) The systematic and rigorous sharing of best practice between and across European cancer healthcare systems and (2) the active promotion of Research and Innovation focused on improving outcomes; (3) Improving access to new and established cancer care by sharing best practice in the development, approval, procurement and reimbursement of cancer diagnostic tests and treatments. Work with other organisations to bring into being a Europe based centre that will (1) systematically identify, evaluate and validate and disseminate best practice in cancer management for the different countries and regions and (2) promote Research and Innovation and its translation to maximise its impact to improve outcomes.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Matikas, Alexios, et al.
(författare)
-
PD-1 protein and gene expression as prognostic factors in early breast cancer
- 2020
-
Ingår i: ESMO Open. - : BMJ Publishing Group Ltd. - 2059-7029. ; 5:6
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is a paucity of data on the prognostic value of programmed cell death protein 1 (PD-1) protein and gene expression in early breast cancer (BC) and the present study's aim was to comprehensively investigate it.Methods: The study consisted of three parts: a correlative analysis of PD-1 protein and gene expression from an original patient cohort of 564 patients with early BC; a systematic review and trial-level meta-analysis on the association between PD-1 protein expression and disease-free survival/overall survival (OS) in early BC; and a pooled gene expression analysis from publicly available transcriptomic datasets regarding PDCD1 expression.Results: In the study cohort, PD-1 protein, but not gene expression, was associated with improved OS (HRadj=0.73, 95% CI 0.55 to 0.97, p=0.027 and HRadj=0.88, 95% CI 0.68 to 1.13, p=0.312, respectively). In the trial-level meta-analysis, PD-1 protein expression was not found to be statistically significantly associated with outcomes in the overall population. Finally, in the pooled gene expression analysis, higher PDCD1 expression was associated with better OS in multivariable analysis in the entire population (HRadj=0.89, 95% CI 0.80 to 0.99, p=0.025) and in basal-like tumours.Conclusions: PD-1 protein and gene expression seem to be promising prognostic factors in early BC. Standardisation of detection and assessment methods is of utmost importance.
|
|
| 25. |
- Matikas, A., et al.
(författare)
-
Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer
- 2021
-
Ingår i: ESMO open. - : Elsevier BV. - 2059-7029. ; 6:2
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Emerging data support the use of thymidine kinase 1 (TK1) activity as a prognostic marker and for monitoring of response in breast cancer (BC). The long-term prognostic value of TK1 kinetics during neoadjuvant chemotherapy is unclear, which this study aimed to elucidate. METHODS: Material from patients enrolled to the single-arm prospective PROMIX trial of neoadjuvant epirubicin, docetaxel and bevacizumab for early BC was used. Ki67 in baseline biopsies was assessed both centrally and by automated digital imaging analysis. TK1 activity was measured from blood samples obtained at baseline and following two cycles of chemotherapy. The associations of TK1 and its kinetics as well as Ki67 with event-free survival and overall survival (OS) were evaluated using multivariable Cox regression models. RESULTS: Central Ki67 counting had excellent correlation with the results of digital image analysis (r= 0.814), but not with the diagnostic samples (r= 0.234), while it was independently prognostic for worse OS [adjusted hazard ratio (HRadj) = 2.72, 95% confidence interval (CI) 1.19-6.21, P= 0.02]. Greater increase in TK1 activity after two cycles of chemotherapy resulted in improved event-free survival (HRadj= 0.50, 95% CI 0.26-0.97, P= 0.04) and OS (HRadj= 0.46, 95% CI 0.95, P= 0.04). There was significant interaction between the prognostic value of TK1 kinetics and Ki67 (pinteraction 0.04). CONCLUSION: Serial measurement of serum TK1 activity during neoadjuvant chemotherapy provides long-term prognostic information in BC patients. The ease of obtaining serial samples for TK1 assessment motivates further evaluation in larger studies. Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Olofsson Bagge, Roger, 1978, et al.
(författare)
-
A phase Ib randomized multicenter trial of isolated hepatic perfusion in combination with ipilimumab and nivolumab for uveal melanoma
- 2024
-
Ingår i: ESMO OPEN. - : Elsevier. - 2059-7029. ; 9:7
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Uveal melanoma (UM) is a rare malignancy where 50% of patients develop metastatic disease primarily affecting the liver. Approximately 40% of patients with metastatic UM respond to one-time isolated hepatic perfusion (IHP) with high -dose melphalan. This phase I trial investigates the safety and clinical ef fi cacy of IHP combined with ipilimumab (IPI) and nivolumab (NIVO). Patients and methods: Immunotherapy-na & iuml;ve patients were randomized in this phase I trial to receive either IHP followed by IPI 3 mg/kg and NIVO 1 mg/kg (IPI3/NIVO1) for four cycles (post -operative arm), or one cycle of preoperative IPI3/NIVO1, IHP and then three cycles of IPI3/NIVO1 (pre-post-operative arm), followed by maintenance therapy with NIVO 480 mg for 1 year. Results: Eighteen patients were enrolled and randomized. Three patients did not undergo IHP as planned. In total, 11/ 18 patients (6 in the post -operative arm and 5 in the pre-post-operative arm) did not complete the planned four cycles of IPI3/NIVO1. Toxicity to IHP was similar in both groups, but the number of immune-related adverse events (AEs) was higher in the pre-post-operative arm. Among assessable patients, overall response rate was 57% in the post -operative arm (4/7) and 22% in the pre-post-operative arm (2/9). Conclusions: Combination therapy with IHP and IPI3/NIVO1 was associated with severe AEs. The ef fi cacy of this combination is encouraging with high response rates. One cycle of preoperative IPI/NIVO before IHP did not show potential bene fi ts in terms of safety or ef fi cacy.
|
|
| 29. |
- Osterlund, P., et al.
(författare)
-
Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours : a multicentre retrospective observational cohort study
- 2022
-
Ingår i: ESMO Open. - : Elsevier. - 2059-7029. ; 7:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce.Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity.Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/ infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11).Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.
|
|
| 30. |
- Paakkola, N.-M., et al.
(författare)
-
The prognostic and predictive impact of low estrogen receptor expression in early breast cancer : a systematic review and meta-analysis
- 2021
-
Ingår i: ESMO Open. - : Elsevier. - 2059-7029. ; 6:6
-
Forskningsöversikt (refereegranskat)abstract
- INTRODUCTION: Traditionally, estrogen receptor (ER)-positive breast cancer has been defined as tumors with ≥1% positive for ER. The updated American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines recommend that tumors with ER expression of 1%-10% should be classified as ER-low-positive, recognizing the limited clinical evidence on the prognostic and predictive role of low ER expression. We aimed to investigate the predictive role of ER-low expression to neoadjuvant chemotherapy (NeoCT) and the prognostic significance of ER-low expressing breast tumors compared with ER-positive or ER-negative breast tumors.METHODS: A meta-analysis was conducted using the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines and eligible articles were identified on PubMed and ISI Web of Science databases. The primary outcome was pathologic complete response and secondary outcomes were disease-free survival (DFS) and overall survival (OS). Twelve retrospective cohort studies were included in the meta-analysis. NeoCT resulted in higher pathologic complete response among patients with ER-low expression compared with ER-positive and comparable to ER-negative. Patients with ER-low breast cancer had a statistically significant worse DFS and OS compared with patients with ER-positive breast cancer, whereas no difference in DFS or OS was observed between ER-low and ER-negative subgroups.DISCUSSION: The current evidence suggests that ER-low breast cancer has a more similar outcome to ER-negative than to ER-positive breast cancer in terms of DFS and OS. ER-low expression seems also to have a predictive role regarding NeoCT. Considering the certainty of current evidence categorized as low to moderate, our results urge the need for well-designed prospective studies investigating the molecular background and the most appropriate treatment strategy for ER-low expressing breast cancer.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Razis, E., et al.
(författare)
-
Assessment of the management of carcinomatous meningitis from breast cancer globally: a study by the Breast International Group Brain Metastasis Task Force
- 2022
-
Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 7:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Carcinomatous meningitis (CM) is a severe complication of breast cancer. The Breast International Group (BIG) carried out a survey to describe the approach to CM internationally. Patients and methods: A questionnaire on the management of CM was developed by the Brain Metastases Task Force of BIG and distributed to its groups, requesting one answer per group site. Results: A total of 241 sites responded, 119 from Europe, 9 from North America, 39 from Central/South America, 58 from Asia, and 16 in Australia/New Zealand, with 24.5% being general hospitals with oncology units, 44.4% university hospitals, 22.4% oncology centers, and 8.7% private hospitals. About 56.0% of sites reported seeing <5 cases annually with 60.6% reporting no increase in the number of cases of CM recently. Nearly 63.1% of sites investigate for CM when a patient has symptoms or radiological evidence, while 33.2% investigate only for symptoms. For diagnosis, 71.8% of sites required a positive cerebrospinal fluid cytology, while magnetic resonance imaging findings were sufficient in 23.7% of sites. Roughly 97.1% of sites treat CM and 51.9% also refer patients to palliative care. Intrathecal therapy is used in 41.9% of sites, mainly with methotrexate (74.3%). As many as 20 centers have a national registry for patients with breast cancer with central nervous system metastases and of those 5 have one for CM. Most (90.9%) centers would be interested in participating in a registry as well as in studies for CM, the latter preferably (62.1%) breast cancer subtype specific. Conclusions: This is the first study to map out the approach to CM from breast cancer globally. Although guidelines with level 1 evidence are lacking, there is a high degree of homogeneity in the approach to CM globally and great interest for conducting studies in this area.
|
|
| 36. |
|
|
| 37. |
- Stacchiotti, S., et al.
(författare)
-
Epithelioid hemangioendothelioma, an ultra-rare cancer : a consensus paper from the community of experts
- 2021
-
Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:3
-
Forskningsöversikt (refereegranskat)abstract
- Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
- Woldmar, N., et al.
(författare)
-
Proteomic analysis of brain metastatic lung adenocarcinoma reveals intertumoral heterogeneity and specific alterations associated with the timing of brain metastases
- 2023
-
Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Brain metastases are associated with considerable negative effects on patients’ outcome in lung adenocarcinoma (LADC). Here, we investigated the proteomic landscape of primary LADCs and their corresponding brain metastases. Materials and methods: Proteomic profiling was conducted on 20 surgically resected primary and brain metastatic LADC samples via label-free shotgun proteomics. After sample processing, peptides were analyzed using an Ultimate 3000 pump coupled to a QExactive HF-X mass spectrometer. Raw data were searched using PD 2.4. Further data analyses were carried out using Perseus, RStudio and GraphPad Prism. Proteomic data were correlated with clinical and histopathological parameters and the timing of brain metastases. Mass spectrometry-based proteomic data are available via ProteomeXchange with identifier PXD027259. Results: Out of the 6821 proteins identified and quantified, 1496 proteins were differentially expressed between primary LADCs and corresponding brain metastases. Pathways associated with the immune system, cell-cell/matrix interactions and migration were predominantly activated in the primary tumors, whereas pathways related to metabolism, translation or vesicle formation were overrepresented in the metastatic tumors. When comparing fast- versus slow-progressing patients, we found 454 and 298 differentially expressed proteins in the primary tumors and brain metastases, respectively. Metabolic reprogramming and ribosomal activity were prominently up-regulated in the fast-progressing patients (versus slow-progressing individuals), whereas expression of cell-cell interaction- and immune system-related pathways was reduced in these patients and in those with multiple brain metastases. Conclusions: This is the first comprehensive proteomic analysis of paired primary tumors and brain metastases of LADC patients. Our data suggest a malfunction of cellular attachment and an increase in ribosomal activity in LADC tissue, promoting brain metastasis. The current study provides insights into the biology of LADC brain metastases and, moreover, might contribute to the development of personalized follow-up strategies in LADC.
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
