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Background: Epidemiological surveys have monitored chronic non-cancer pain (CNCP) and investigated associated factors in Denmark for more than 20 years. This study aimed to analyse CNCP prevalence in the Danish population from 2000 to 2023 and its associations with mental health status and loneliness., Methods: Population-based surveys were conducted between 2000 and 2023. In all waves, residents aged ≥ 16 years were randomly selected to complete a self-administered questionnaire. Samples included 10,089 respondents in 2000, 5292 in 2005, 14,330 in 2010, 13,429 in 2013, 13,050 in 2017, 10,384 in 2021 and 9303 in 2023. CNCP was defined as pain lasting ≥ 6 months. Mental status was assessed by Mental Component Summary score of Short Form-12 and severe loneliness by the Three-Item Loneliness Scale. Calibration weighting was applied to reduce potential non-response bias., Results: The prevalence of CNCP increased steadily by 9.4 percentage points from 2000 (19.5%) to 2023 (28.9%), but with a downward tick during the COVID-19 pandemic in 2021 (25.3%). Women aged 45 years or older had the highest prevalence in all waves. Results showed a worsening of mental health over time in both individuals with and without CNCP; however, the lowest scores were reported by individuals with CNCP. Severe loneliness seemed to be a substantial problem in individuals with CNCP (17.3% in 2021)., Conclusions: In summary, CNCP was highly prevalent over the given period and associated with mental health status and severe loneliness in recent years., Significance: This study demonstrated alarming trend on chronic non-cancer pain prevalence over time in Denmark. The high estimates of prevalence and related issues, such as mental health and severe loneliness deserve further investigation and prioritisation in the public health agenda., (© 2024 European Pain Federation ‐ EFIC ®.)

Importance: Endocrine treatments, such as Tamoxifen (TAM) and/or Aromatase inhibitors (AI), are the adjuvant therapy of choice for hormone-receptor positive breast cancer. These agents are associated with menopausal symptoms, adversely affecting drug compliance. Topical estrogen (TE) has been proposed for symptom management, given its' local application and presumed reduced bioavailability, however its oncological safety remains uncertain., Objective: The present systematic review, meta-analysis and expert panel review aimed to evaluate the strength of the available evidence on the risk of recurrence and mortality when TE is utilised in congruence with TAM or AI treatment, among BC survivors., Data Sources: Six databases and two prospective registers, were interrogated from inception to January 3rd, 2024. Search terms were Breast cancer AND Hormone replacement therapy AND topical/vaginal oestrogen AND recurrence/mortality., Study Selection: All study designs reporting the use vs. non-use of TE in breast cancer survivors receiving adjuvant endocrine treatment were included. Six observational studies were deemed eligible for inclusion., Data Extraction and Synthesis: Sources of heterogeneity were explored using subgroup analysis by risk of bias, median follow-up period, node positivity and menopausal status. Trial sequential analysis was performed to quantify outcome reliability. A global expert panel was called to deliberate on the data, pinpoint areas of limited understanding, and determine the most important areas for future research., Main Outcomes and Measures: Risk ratio effect sizes (RR) and corresponding 95 % Confidence Intervals (CI) of breast cancer recurrence and mortality in survivors on endocrine treatment (TAM and/or AI) exposed to TE were reported. Expert panel appraisal of meta-analysis evidence with definition of current knowledge gaps and future research aims., Results: In 38 050 female patients receiving adjuvant endocrine treatment, of whom 1805 had been exposed to TE, TE exposure of those on AI, did not increase all-cause mortality (RR 0.99 [95 %CI 0.58, 1.69], I 2  = 81 %, P = 0.96; moderate GRADE certainty). However, such exposure may convey an increased risk of recurrence (RR 2.51 [95 % CI 1.10, 5.72], I 2  = 9 %, P = 0.03; low-GRADE certainty). Exposure to TE during TAM did not increase either recurrence risk or all-cause mortality. Clinical factors such as lymph node positivity at the time of diagnosis and menopausal status and follow-up time appeared to be significant confounders., Conclusions and Relevance: The use of TE does not appear to increase either recurrence or mortality risk among BC survivors treated with TAM. An increased recurrence risk, without an increase in mortality, cannot be ruled out when TE is used during AI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose limiting adverse effect that may be transient or become persistent after the treatment ended. The taxane paclitaxel induces CIPN in 57-83% of patients treated. The neuropathy may debut or progress after the end of treatment (EOT), known as coasting, but little is known about the incidence of this phenomenon. The aim of this review is to examine the incidence and severity of coasting in CIPN in patients with breast cancer. Patient/material and methods: MEDLINE, Embase, clinicaltrials.gov, and medrivx.org were searched using terms related to taxanes, adverse effects, and breast cancer. Studies had to have a follow-up time of at least 3 months after EOT and patients had to have received taxanes in monotherapy. Additionally, studies had to be longitudinal and describe the neuropathy assessment method and timing., Results: A total of 17 studies met the eligibility criteria, with 4,265 participants summarized. Of these, one study reported coasting events in 14.3% (n = 4) of patients. Eight studies reported no coasting events and eight were unclear., Interpretation: Few studies reported on coasting in CIPN. There may be several reasons for this, including the timing and choice of assessment methods, confounding factors, and the possible rarity of the phenomenon. More information is needed about coasting in CIPN to better characterize the neuropathies, guide patient and doctor decisions, and aid in the development of interventions toward CIPN.

Objective: This study investigated the association between loss of MSH2/MSH6 versus loss of MLH1/PMS2 expression and overall survival and disease-free survival in patients with localized colorectal cancer., Background: The risk of developing colorectal cancer varies depending on the expression of mismatch repair proteins. However, it is unknown if the prognosis differs accordingly., Methods: In this retrospective study, we included a Danish cohort of patients who underwent surgery for colorectal cancer between 2009 and 2020. The Danish Colorectal Cancer Group database was used to identify patients, and patient-level data were extracted from six registries. Subsequently, patients with proficient mismatch repair status, with metastatic disease, who underwent emergency surgery, or who received neoadjuvant therapy were excluded. Patients were then propensity score matched in a 1:1 ratio., Results: A total of 3,625 patients with localized deficient mismatch repair colorectal cancer were included in the study. Patients had a median age of 75 years and a median follow-up of 4.3 years. Before matching, the MSH2/MSH6 versus MLH1/PMS2 groups differed in age, gender, and comorbidities. After matching, 556 patients were included and loss of MSH2/MSH6 was significantly associated with better overall survival (hazard ratio 0.60; 95% CI, 0.37-0.94); however, not disease-free survival (hazard ratio 0.84; 95% CI, 0.54-1.30)., Conclusions: In patients with localized deficient mismatch repair colorectal cancer who underwent surgery, a significant association was found between loss of MSH2/MSH6 versus loss of MLH1/PMS2 expression and overall survival. Thus, these patients may be a target for a differentiated follow-up strategy., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: Radiation induced image changes (IC) on MRI have been observed after proton therapy for brain tumours. This study aims to create predictive models, with and without taking into account patient variation, based on dose, linear energy transfer (LET) and periventricular zone (PVZ) in a national cohort of patients with glioma treated with pencil beam scanning (PBS)., Materials and Methods: A cohort of 87 consecutive patients with oligodendroglioma or astrocytoma (WHO grade 2-4) treated with PBS from January 2019 to December 2021 was included. All patients were treated with three to four beams. Monte Carlo calculations of dose and LET were performed for all treatment plans. Lesion weighted as well as mixed effect logistic regression models were developed to predict IC in a voxel., Results: 12 patients (14 %) developed ICs on the follow-up MR-scans. Mixed effect modelling accounting for interpatient variation was justified by the non-negligible inter class correlation coefficient (ICC = 0.33). The two approaches identified similar model features and marginal improvement in model performance was found, when increasing model parameters from two (AUC = 0.92/0.94) to three (AUC = 0.93/0.95) parameters. Univariate analysis showed that patients treated with narrow beam configurations had an increased incidence of IC (p = 0.01)., Conclusion: 14% of patients developed IC following PT. Lesion-weighted and mixed effect models resulted in similar model performance confirming increased risk of IC with increasing LET. The beam arrangement seems to influence the risk of IC and needs further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: There are no approved treatments specifically for low grade serous ovarian cancer; current standard of care treatment options are limited in efficacy and tolerability. The combination of avutometinib with defactinib has demonstrated efficacy and a consistent safety profile in two clinical trials in recurrent low grade serous ovarian cancer, and a lower discontinuation rate due to adverse events compared with historical rates for standard of care., Primary Objective: To compare the progression free survival of the combination of avutometinib with defactinib versus investigator's choice of treatment in patients with recurrent low grade serous ovarian cancer., Study Hypothesis: Combination treatment with avutometinib-defactinib will significantly improve progression free survival compared with investigator's choice of treatment in patients with recurrent low grade serous ovarian cancer., Trial Design: GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301 is a phase 3, randomized, international, open label study designed to compare avutometinib with defactinib versus investigator's choice of treatment in patients with recurrent low grade serous ovarian cancer who have progressed on a previous platinum based therapy. On confirmation of disease progression using a blinded independent central review, patients on the investigator's choice of treatment arm may cross over to the avutometinib-defactinib arm., Major Inclusion/exclusion Criteria: Patients must have recurrent low grade serous ovarian cancer ( KRAS mutant or wild-type) and have documented progression (radiographic or clinical) or recurrence of low grade serous ovarian cancer after at least one platinum based chemotherapy regimen. Unlimited additional previous lines of therapy are allowed, including previous MEK/RAF inhibitor. Patients will be excluded if they have co-existing high grade ovarian cancer or had previous treatment with avutometinib, defactinib, or any other FAK inhibitor., Primary Endpoint: Progression free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, blinded-independent central review., Sample Size: Approximately 270 patients will be randomized in a 1:1 fashion to either the combination avutometinib with defactinib arm (n~135) or the investigator's choice of treatment arm (n~135)., Estimated Dates for Completing Accrual and Presenting Results: The estimated primary completion date of RAMP 301 is 2028, and the estimated study completion date is 2031., Trial Registration: ClinicalTrials.gov NCT06072781., Competing Interests: Competing interests: YCL discloses institutional research grants from BeiGene and honoraria from AstraZeneca. CAA discloses institutional trial funding from Abbvie, Artios Pharma, AstraZeneca, Clovis, and Genentech/Roche. PT discloses advisory board participation with Iovance, AstraZeneca, Clovis, GSK, Seagen, Agenus, Relacorilant, Immunogen, Mersana, Novocurfe, Zentalis, Merck, and Caris. RLC discloses grants from AstraZeneca, Clovis, Genelux, Genmab, Merck, Immunogen, Roche/Genentech, Karyopharm, royalties from Up To Date, and consulting fees or honoraria from Agenus, Alkermes, AstraZeneca, Clovis, Deciphera, Genelux, Genmab, GSK, Immunogen, OncoQuest, Onxerna, Regeneron, Karyopharm, Roche/Genentech, Novocure, Merck, and Abbvie. BJM discloses consulting fees or honoraria from Acrivon, Adaptimmune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, CLovis, Eisai, Elevar, EMD Merck, Genmab, GOG Foundation, Gradalis, Heng Rui, Immunogen, Karyopharm, Iovance, Laekna, Macrogenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, GSK, Sorrento, USO, VBL, Verastem, and Zentalis. DG discloses royalties from UpToDate and Elsevier, consulting fees from Verastem, honoraria from Johns Hopkins, and stock in BMS, J&J, Proctor, and Gamble. RG discloses consulting fees from GSK, AstraZeneca, Myriad, Natera, GOG Foundation, honoraria from PRIME, IDEOlogy, Curio, and funding support by the NIH/NCI cancer center support grant P30 CA 008748. KNM discloses institution research funding from PTC therapeutics, Lilly, Clovis, Genentech, GSK, Verastem, royalties from UpToDate, and consulting fees or honoraria from AstraZeneca, Aravive, Aadi, Blueprint, Clovis, Caris, Duality, Eisai, GSK, Genentech/Roche, Hengrui, Immunogen, Iovance, Janssen, Lilly, Mereo, Mersana, Merck, Myriad, Novartis, Novocure, Pannavance, Onconova, VBL, Verastem, Zentalia, PRIME, RTP, Medscape, Great Debates, and Updates. PH discloses grants or honoraria from AstraZeneca, Roche, GSK, Genmab, Immunogen, Seagen, Clovis, Novartis, Amgen, Mersana, Sotio, Stryker, Zai Lab, MSD, Clovis, Eisai, Daiichi Sankyo, and Karyopharm. MRM discloses consulting fees from GSK, AstraZeneca, Immunogen, Merck, Merck KGA, and stock and leadership position with Karyopharm. AO discloses consulting fees or honoraria from Agenus, AstraZeneca, Clovis, Corcept, Deciphera, Daiichi Sankyo, Debiopharm, Eisai, Exelixis, Roche, Genmab, GSK, Immunogen, Itheos, MSD, Mersana, Myriad, Novocure, OncoXerna, PharmaMar, Regeneron, Shattuck Labs, Seagen, Sutro, TORL, Zentalis, and Zymeworks. DMO discloses institutional research funds from Abbvie, Advaxis, Agenus, Alkermes, Aravive, Arcus, AstraZeneca, BeiGene, Boston Biomedical, BMS, Clovis, Deciphera, Eisai, EMD Serono, Exelixis, Genentech, Genmab, GSK, Roche, Immunogen, Incyte, Iovance, Karyopharm, Leap, Merck, Mersana, NCI, Novartis, Novocure, OncoC4, OncoQuest, Pfizer, Precision Therapeutics, Prelude, Regeneron, RTOG, Seagen, Sutro, and SWOG, consulting fees from Abbvie, Adaptimmune, Agneus, Arquer, Arcus, AstraZeneca, Atossa, Boston Biomedical, Cardiff Oncology, Celcuity, Clovis, Corcept, Duality Bio, Eisai, Elevar, Exelixis, Genetech, Genelux, GSK, Roche, Immunogen, Imvax, Intervenn, InxMed, Iovance, Janssen, Jazz, Laekna, Leap, Luzsana Biotechnology, Merck, Mersana Myriad, Novartis, Novocure, OncoC4, Onconova, Regeneron, RepImmune, RPharm, Roche, SeaGen, Sorrento, Sutro, Tarveda, Toray, Trillium, Umoja, Verastem, VBL, Vincerx Pharma, Xencor, and Zentalis. AMO discloses institutional funding from AstraZeneca, and Amgen. SB discloses consulting fees or honoraria from AstraZeneca, Epsilogen, GSK, Immunogen, ITM Oncologics, MSK, Mersana, Myriad, Novartis, Oncxerna, Seagen, Shattuck, Regeneron, Verastem, Abbvie, Pfizer, Takeda, and Novocure. EVN discloses consulting fees or honoraria from AstraZeneca, Oncoinvent, Regeneron, GSK, and Merck. NC discloses consulting fees or honoraria from Novocure, AstraZeneca, Clovis, Eisai, GSK, Immunogen, Mersana, MSD, Pfizer, Roche/Genentech, Pieris, and Novartis., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objective: In the ENGOT-EN6-NSGO/GOG3031/RUBY trial, dostarlimab+carboplatin-paclitaxel demonstrated significant improvement in progression free survival and a positive trend in overall survival compared with placebo+carboplatin-paclitaxel, with manageable toxicity, in patients with primary advanced or recurrent endometrial cancer. Here we report on patient-reported outcomes in the mismatch repair-deficient/microsatellite instability-high population, a secondary endpoint in the trial., Methods: Patients were randomized 1:1 to dostarlimab+carboplatin-paclitaxel or placebo+carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo monotherapy every 6 weeks for ≤3 years or until disease progression. Patient-reported outcomes, assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Endometrial Cancer Module, were prespecified secondary endpoints. A mixed model for repeated measures analysis, a prespecified exploratory analysis, was conducted to generate least-squares means to compare between-treatment differences while adjusting for correlations across multiple time points within a patient and controlling for the baseline value. Results are provided with 2-sided, nominal p values., Results: Of 494 patients enrolled, 118 were mismatch repair-deficient/microsatellite instability-high. In this population, mean change from baseline to end of treatment showed visual improvements in global quality of life (QoL), emotional and social function, pain, and back/pelvis pain for dostarlimab+carboplatin-paclitaxel. Meaningful differences (least-squares mean [standard error]) favoring the dostarlimab arm were reported for change from baseline to end of treatment for QoL (14.7 [5.45]; p=0.01), role function (12.7 [5.92]); p=0.03), emotional function (14.3 [4.92]; p<0.01), social function (13.5 [5.43]; p=0.01), and fatigue (-13.3 [5.84]; p=0.03)., Conclusions: Patients with mismatch repair-deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer receiving dostarlimab+carboplatin-paclitaxel demonstrated improvements in several QoL domains over patients receiving placebo+carboplatin-paclitaxel. The observed improvements in progression free survival and overall survival while improving or maintaining QoL further supports dostarlimab+carboplatin-paclitaxel as a standard of care in this setting., Trial Registration: ClinicalTrials.gov NCT03981796., Competing Interests: Competing interests: GV reports consulting fees from GSK; honoraria from AstraZeneca, GSK, and MSD; travel support from AstraZeneca and PharmaMar; participation in advisory boards for AstraZeneca, Eisai, GSK, and MSD. MAP reports consulting fees from GSK, Tesaro, Merck, Eisai, SeaGen, Clovis Oncology, and AstraZeneca. SH reports consulting fees from AstraZeneca, Eisai, GSK, and MSD and honoraria from AstraZeneca and GSK. EMM reports advisory board meeting fees from AstraZeneca, GSK, and Tempus; honoraria from OncLive and Opinions in Gyn Malignancies; and support for attending meetings from Opinions in Gyn Malignancies and OncLive. ZN reports honoraria from Sofmedica, AstraZeneca, and MSD; support for attending meetings from Sofmedica and Preglem; participation on a data safety monitoring board or advisory board for AstraZeneca and Richter Gedeon; stock options from Richter Gedeon; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from AstraZeneca. RH reports honoraria from GSK, AstraZeneca, Clovis Oncology, Eisai, and Merck. DD reports receiving consulting fees from AstraZeneca, GSK/Tesaro, Roche, Eisai Germany, and MSD Oncology; honoraria for advisory roles from Roche, AstraZeneca, GSK/Tesaro, Intuitive Surgical, KLS Martin, MSD, PharmaMar, and Seagen; and travel support from AstraZeneca. TM reports honoraria from Immunogen. LG reports institutional grants from Alkermes, AstraZeneca, Clovis Oncology, Esperas, IMV, ImmunoGen, Karyopharm, MSD, Mersana, Novocure, OncoQuest Pharmaceuticals, Pfizer, Roche, and Tesaro; consulting fees from Merck; honoraria from Alkermes, AstraZeneca, Eisai, Eisai-Merck, and GSK. BA reports honoraria from AstraZeneca, Eisai, GSK, MSD, Norartis, and Roche; support for attending meetings from AstraZeneca, GSK, and Roche; participation on a data safety monitoring board or advisory board for Eisai, GSK, MSD, Roche, and Sanofi Aventis. RG reports participation on a data safety monitoring board or advisory board for Pionyr Pharmaceuticals and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Bausch+Lomb. NC reports advisory board fees for Aadii, GSK, Kartos, Novita Pharmaceuticals, Tarveda Therapeutics, Toray, Umoja, and Zentalis. BJM reports consulting fees from Agenus, Akeso Biopharma, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, Macrogenics, Mersana, Myriad, Novartis, Novocure, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, and VBL and speakers’ bureau honoraria from AstraZeneca, Clovis Oncology, Eisai, Merck, Roche/Genentech, and Tesaro/GSK. TJH reports personal consulting fees from Aadi, AstraZeneca, Caris, Clovis Oncology, Eisai, Epsilogen, Genentech, GSK, Immunogen, J&J, Merck, Mersana, and Seagen; participation on a data safety monitoring board or advisory board for Corcept; and leadership role on the GOG Foundation Board and President of GOG Partners. AS reports royalties as an UptoDate reviewer. BP reports institutional grant support from AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, SeaGen, Sutro Biopharma, Takeda Pharmaceuticals, Tesaro/GSK, Toray, and VBL Therapeutics; consulting fees from AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, I-Mab Biopharma, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, and Toray; support for attending meetings from GOG Foundation; advisory board fees from Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Eisai, Elevar Therapeutics, GOG Foundation, I-Mab Biopharma, Lilly, Merck, Mersana, Seagen, Sutro Biopharma, Tesaro/GSK, Toray, and VBL Therapeutics; and noncompensated leadership fees from NYOB Society Secretary, SGO Clinical Practice Committee Chair, and SGO COVID-19 Taskforce Co-Chair. AAS reports support paid to her institution from GSK for the present IGCS abstract; institutional grant support from AbbVie, Aravive, AstraZeneca, Clovis Oncology, Eisai, Ellipses, I-Mab Biopharma, Immunogen, Merck, Oncoquest/Canaria Bio, Roche/Genentech, Seagen, TapImmune, Tesaro/GSK, and VBL Therapeutics; honoraria from @Point of Care Clinical Care Options Curio Science, Peerview, Bio ASCEND, RTP, GOG Foundation (Highlight reel), and GOG Foundation Symposium; patent issued for 'blood based biomarkers in ovarian cancer'; noncompensated participation on a data safety monitoring board/advisory board from AstraZeneca, Clovis Oncology, Gilead, Immunogen, Imvax, Merck, Mersana, Natera, Onconova, and OncoQuest; uncompensated leadership roles with SGO, AAOGF, and NRG and compensated role from GOG; receipt of medical writing support from AstraZeneca; and uncompensated Clinical Trial Steering Committees for the AXLerate trial (Aravive), AtTEnd trial (Hoffman-LaRoche), Oval Trial (VBL Therapeutics), FLORA-5 trial (CanariaBio), and QPT-ORE-004 (CanariaBio). DC reports consultant fees from AstraZeneca and GSK and honoraria from AstraZeneca, GSK, Seagen/Genmab, and Immunogen. MRM reports consulting fees from AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, and Zai Lab; speakers’ bureau fees from AstraZeneca and GSK; research funding (to institution) from Apexigen, AstraZeneca, Deciphera (trial chair), GSK, and Ultimovacs; and personal financial interest in Karyopharm (stocks/shares, member of board of directors). DB reports institutional grant fees from GSK; fees for being a member of GOG Partners Investigational Council; and medical director/owner of Trials365. AMT, KPP, EF, OZ, LML, IP, and SS have nothing to disclose. OM, VV, and JG are employees of GSK., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Purpose: The introduction of immunotherapy in pleural mesothelioma (PM) has highlighted the need for effective outcome predictors. This study explores the role of [18F]FDG PET/CT in predicting outcomes in PM treated with immunotherapy., Methods: Patients from the NIPU trial, receiving ipilimumab and nivolumab +/- telomerase vaccine in second-line, were included. [18F]FDG PET/CT was obtained at baseline (n = 100) and at week-5 (n = 76). Metabolic tumour volume (MTV) and peak standardised uptake value (SUV peak ) were evaluated in relation to survival outcomes. Wilcoxon rank-sum test was used to assess differences in MTV, total lesion glycolysis (TLG), maximum standardised uptake value (SUV max ) and SUV peak between patients exhibiting an objective response, defined as either partial response or complete response according to the modified Response Criteria in Solid Tumours (mRECIST) and immune RECIST (iRECIST), and non-responders, defined as either stable disease or progressive disease as their best overall response., Results: Univariate Cox regression revealed significant associations of MTV with OS (HR 1.36, CI: 1.14, 1.62, p < 0.001) and PFS (HR 1.18, CI: 1.03, 1.34, p = 0.02), while multivariate analysis showed a significant association with OS only (HR 1.35, CI: 1.09, 1.68, p = 0.007). While SUV peak was not significantly associated with OS or PFS in univariate analyses, it was significantly associated with OS in multivariate analysis (HR 0.43, CI: 0.23, 0.80, p = 0.008). Objective responders had significant reductions in TLG, SUV max and SUV peak at week-5., Conclusion: MTV provides prognostic value in PM treated with immunotherapy. High SUV peak was not associated with inferior outcomes, which could be attributed to the distinct mechanisms of immunotherapy. Early reductions in PET metrics correlated with treatment response., Study Registration: The NIPU trial (NCT04300244) is registered at clinicaltrials.gov. https://classic., Clinicaltrials: gov/ct2/show/NCT04300244?cond=Pleural+Mesothelioma&cntry=NO&draw=2&rank=4., Competing Interests: Declarations. Ethics approval: The trial was approved by the regional ethics committee (20/47804) and each site ethics committee and was conducted in accordance with the Declaration of Helsinki of the World Medical Association and ICH E6 for Good Clinical Practice. Consent to participate: All patients provided written informed consent. Consent to publish: The authors affirm that human research participants provided informed consent for publication of the images in Figures 6, 7, 8. Competing Interests: ST - External speaker BMS WMS – no conflict of interest EH – no conflicts of interest JBS - BMS Advisory Board ÅH - Advisory/consultancy/meeting presentation roles for AbbVie, AstraZeneca, BMS, Pfizer, Roche, Janssen, MSD, Sanofi, Bayer, Medicover, and Takeda with honoraria directed to own institution, and receiving research grants from Roche, BMS, Ultimovacs, AstraZeneca, Novartis, InCyte, Eli Lilly, Illumina, Merck, Nanopore, GlaxoSmithKline. AKN – Astra Zeneca DSMB; Research funding to institution from Astra Zeneca. ÅKÖ - no disclosures. VDH: Advisory boards: Astra Zeneca, Novartis, Lectures/text: Astra Zeneca, Pfizer, Janssen, BMS, Takeda EM – no conflicts CM – no conflict of interest LTM: No conflicts of interest RF – advisory/consultancy for AIQ Solutions RF – advisory/consultancy for AIQ Solutions SSN-no conflict of interest SF - Advisory/consultancy/meeting presentation MSD, Astra Zeneca, Pfizer MS – no disclosures, (© 2024. The Author(s).)

Significance: The presented retrospective analysis suggests, to the best of our knowledge for the first time, a potential significant interaction between statins and niraparib in clinical settings. Nevertheless, further investigations are required to gain a better understanding of the potential clinical benefit., (©2024 The Authors; Published by the American Association for Cancer Research.)

Purpose: The CDK4/6 inhibitor palbociclib inhibits cyclin A, which is overexpressed in endometrial cancer. Combining palbociclib with endocrine therapy improves efficacy in hormone receptor-positive breast cancer. We investigated palbociclib combined with endocrine therapy for estrogen receptor-positive advanced/recurrent endometrial cancer., Patients and Methods: This placebo-controlled double-blind, randomized phase II screening trial (NCT02730429) enrolled women with measurable/evaluable estrogen receptor-positive endometrioid endometrial cancer that was primary metastatic or had relapsed after ≥1 prior systemic therapy. Patients were randomized in a 1:1 ratio, stratified by number of prior chemotherapy lines, measurable versus evaluable non-measurable disease, and prior medroxyprogesterone/megestrol acetate treatment, to receive oral letrozole 2.5 mg on days 1-28 plus either oral palbociclib 125 mg or placebo on days 1-21, repeated every 28 days until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression-free survival (PFS)., Results: Among 77 patients randomized between February 16, 2017, and December 21, 2018, 73 were treated (36 with palbociclib-letrozole, 37 with placebo-letrozole). Median follow-up was 21.9 (95 % CI, 16.7 to 22.3) months. Median PFS was 8.3 (95 % CI, 4.6 to 11.2) versus 3.1 (95 % CI, 2.7 to 6.8) months, respectively. In a landmark analysis at 12 months the PFS hazard ratio was 0.57 (95 % CI, 0.32 to 0.99; P = .044). Grade ≥ 3 adverse events were more common with palbociclib-letrozole (67 %) than placebo-letrozole (30 %), most commonly neutropenia (44 % v 0 %, respectively)., Conclusion: These results support a potential role of the palbociclib-letrozole combination as treatment for hormone receptor-positive advanced/recurrent endometrial cancer. Based on these encouraging results, phase III evaluation of letrozole combined with a CDK4/6 inhibitor is planned., Clinical Trial Information: NCT02730429., Competing Interests: Declaration of competing interest MRM reports leadership roles and stock for Karyopharm Therapeutics and Sera Prognostics; honoraria from Roche, AstraZeneca, Genmab/Seattle Genetics, GSK, Merck, Mersana, Takeda, Zai Lab, Geneos, and Allarity Therapeutics; consulting/advisory roles for AstraZeneca, Genmab, Karopharm Therapeutics, Pfizer, and GSK; research funding (to institution) from AstraZeneca, Boehringer Ingelheim, Pfizer, Tesaro, Clovis Oncology, Ultimovacs, Apexigen, and GSK; grants and personal fees from Tesaro, AstraZeneca, Pfizer, and Clovis Oncology; travel/accommodation/expenses from AstraZeneca, Karyopharm Therapeutics, Pfizer, Roche, Tesaro, and SeraCare; and other relationships with ENGOT, GCIG, and ESGO. LB reports speaker's bureau participation for GSK and MSD and research funding from AstraZeneca. FM reports honoraria from Roche/Genentech, Novartis, Pfizer, AstraZeneca, Clovis Oncology, Eisai, Genomic Health, PharmaMar, Amgen, MSD Oncology, Seagen, Myriad Genetics, Pierre Fabre, GSK, Agendia, Lilly, Gilead, Daiichi Sankyo, and Immunomedics; consulting/advisory roles for Pfizer, Genomic Health, CureVac, Amgen, Eisai, GSK, Gilead, Seagen, Clovis Oncology, AstraZeneca, Roche, Vaccibody, and Immunomedics; research funding from Roche/Genentech, Novartis, AstraZeneca, Tesaro, Clovis Oncology, MSD Oncology, Vaccibody, Gilead, and GSK; and travel/accommodation/expenses from Roche, Pfizer, AstraZeneca, and Gilead Sciences. RdPC reports employment and stock ownership from Y-mAbs Therapeutics and consulting/advisory role for Karyopharm. MGM reports consulting/advisory roles for AstraZeneca; speakers' bureau for GSK and MSD Oncology; and travel/accommodation/expenses from AstraZeneca, GSK, and MSD Oncology. AA reports consulting/advisory roles and travel/accommodation/expenses from GSK and MSD. BA reports honoraria from Roche, AstraZeneca, MSD, GSK, Eisai Europe, Novartis, Lilly, and Pfizer; consulting/advisory roles for Roche, MSD, Sanofi Aventis GmbH, GSK, and Eisai Europe; and travel/accommodation/expenses from Roche, AstraZeneca, GSK, Lilly, and Daiichi Sankyo/AstraZeneca. VS reports honoraria from AstraZeneca, MSD Oncology, GSK, PharmaMar, and Novocure; consulting/advisory roles for AstraZeneca and Novocure; and travel/accommodation/expenses from GSK and PharmaMar. AR reports consulting/advisory roles for AstraZeneca, GSK, Boehringer Ingelheim, MSD, and Pharma&; speakers' bureau for AstraZeneca, GSK, MSD, and Pharma&; and travel/accommodation/expenses from AstraZeneca. KL reports honoraria from AstraZeneca; consulting/advisory roles for Eisai, MSD, GSK, and Nycode; research funding (inst) from GSK; and is Deputy Medical Director of NSGO-CTU. FT reports research funding and personal fees from AstraZeneca, Clovis, Eisai, ImmunoGen, MSD, SAGA diagnostics, and Tesaro/GSK. MPBG reports consulting/advisory roles for AstraZeneca, GSK, MSD Oncology, Eisai Europe, Clovis Oncology, PharmaMar, and Pharma&; speakers' bureau for AstraZeneca Spain, GSK, Eisai Europe, and MSD Oncology; and travel/accommodation/expenses from AstraZeneca, GSK, and MSD Oncology. JEK reports employment (immediate family member) with MSD; consulting/advisory roles for AstraZeneca, MSD, and GSK; and travel/accommodation from AstraZeneca, Eisai, PharmaMar, and GSK. JS reports honoraria from AstraZeneca, Eisai, Clovis Oncology, Olympus Medical Systems, Johnson & Johnson, PharmaMar, Pfizer, Teva, Tesaro, MSD Oncology, GSK, and Bayer; consulting/advisory roles for AstraZeneca, Clovis Oncology, PharmaMar, Merck, Pfizer, Tesaro, MSD Oncology, Lilly, Novocure, Johnson & Johnson, Roche Diagnostics, NGRESS-Health, Riemser, Sobi, GSK, Novartis, and Alkermes; research funding (inst) from AstraZeneca, Clovis Oncology, Merck, Bayer, PharmaMar, Pfizer, Tesaro, MSD Oncology, and Roche; travel/accommodation/expenses from AstraZeneca, Clovis Oncology, PharmaMar, Roche Pharma AG, Tesaro, MSD Oncology, and Olympus. No other potential conflicts of interest were reported., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cutaneous T-cell lymphomas (CTCL) are a rare collection of diseases, frequently associated with diagnostic challenges and complex management dilemmas. The multidisciplinary team is vital for accurate clinico-pathological diagnoses and for collaborative therapeutic decisions throughout the management journey, which frequently involves multiple lines of therapy. Radiotherapy (RT) is a highly effective skin-directed therapy for CTCL, commonly delivered as localised fields or as total skin electron beam therapy (TSEBT). Mycosis fungoides (MF) is the most common of the CTCL, and patients typically experience high rates of morbidity and long natural histories of relapse and progression. Patients with MF typically present with incurable disease; in these patients, RT has an established role in symptom- and disease-control, achieving excellent response rates and proven therapeutic benefits. The role of RT continues to evolve, with modern practices favouring lower doses to reduce toxicity risks and allow for re-irradiation. Less commonly, there are situations where RT has an integral role in the potential cure of patients with MF: firstly, in the setting of unilesional MF where localised RT alone may be curative, and secondly, in the setting of preconditioning prior to curative-intent allogeneic hematopoietic stem cell transplant for patients with advanced MF/Sezary syndrome, where conventional-dose TSEBT is indicated as the most effective single agent for maximal debulking of skin disease. Radiotherapy also has an important role in the management of the less common CTCL, including the curative treatment of localised primary cutaneous anaplastic large cell lymphoma. Despite proven efficacy and quality of life benefits, disparity exists in access to RT and TSEBT. World-wide, stronger multidisciplinary collaborations and greater patient advocacy are required to increase access to RT and improve equity of care for our patients with CTCL., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cystic fibrosis (CF) is an incurable, progressive disease that affects multiple organs, causing burdensome symptoms. This study aimed to explore the palliative care needs in patients with CF, focusing on health-related quality of life (HRQOL), fatigue, anxiety and depression., Methods: From October 2019 to March 2020, a cross-sectional questionnaire survey was conducted with outpatients with CF at the Infectious Medicine Clinic in a Danish University Hospital., Results: 130 patients completed at least one questionnaire. Mean age was 35.5 years (SD 11.5), with 51.7% males. Charlson's comorbidity index mean score was 1.3 (SD 1.6). Patients with CF had significantly lower scores in general health, vitality, social functioning, role emotional and mental health compared with the Danish population. Mean fatigue score of patients was 50.9 (SD 16.2), with the highest scores in general fatigue, physical fatigue and reduced activity. Additionally, 33% indicated anxiety and 19.5% depression. 51.6% were treated with Tezacaftor/Ivacaftor or Lumacaftor/Ivacaftor., Conclusion: This study found poor HRQOL and burdensome symptoms of fatigue, anxiety and depression in patients with CF compared with the general Danish population. The results suggest that systematic assessments and palliative care interventions should be integrated into routine CF care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Diagnostic and therapeutic management of patients with head and neck squamous cell carcinoma of unknown primary (HNSCCUP) remains a challenge. The aim of the present phase IV study was to assess adherence to the current Danish guidelines and evaluate the treatment outcome in HNSCCUP patients., Materials and Methods: Prospectively collected data in the DAHANCA database from patients treated between 2014 and 2020 was evaluated. The median follow-up was 6.7 years. Treatment included definitive neck dissection (dND), primary (chemo-)radiotherapy ((C-)RT), neck dissection (ND) followed by postoperative (C-)RT (ND + (C-)PORT). Outcome were reported as five-year estimates of loco-regional failure (LRF), ultimate LRF (ULRF), disease specific mortality (DSM), overall survival (OS), and toxicity scores ≥ 3., Results: A total of 288 patients were treated, of which 254 (88 %) received treatment with curative intent and were eligible for adherence assessment. These were allocated to dND (n = 60), (C-)RT (n = 81) and ND + (C-)PORT (n = 113). The HPV/p16 status was known in 95 % of patients with 109 (43 %) positive cases. The 5-year LRF, DSM, and OS for patients treated with curative intent was 22 %, 15 % and 73 %, and in patients with p16 positive disease 16 %, 5 %, and 85 %. The overall guideline adherence was 76 % (192/254). In the adherent group the LRF, ULRF, DSM, and OS were 22 %, 11 %, 16 %, and 73 %, respectively., Conclusion: The study revealed good treatment outcome measures in HNSCCUP patients subject to the Danish guidelines, comparable to other head and neck cancer patients. The observed guideline-deviations did not affect outcome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This clinical trial investigated the safety and efficacy of single-cycle pembrolizumab in patients with localized deficient mismatch repair (dMMR) colon cancer., Background: Neoadjuvant immunotherapy has induced remarkable rates of pathological complete response in patients with dMMR colon cancer. However, the optimal length and type of treatment are yet to be determined., Methods: This was an investigator-initiated, multicenter, single-arm, phase II study (ClinicalTrials.gov: NCT05662527) investigating the safety and efficacy of neoadjuvant pembrolizumab in patients with stage I-III dMMR colon cancer. Patients received a single cycle of pembrolizumab 4 mg/kg (maximum 400 mg) and underwent surgery three to five weeks later. An interim safety and efficacy analysis after including 42 patients was pre-planned. The primary outcomes were safety and efficacy (pathological complete response in more than 20% of patients)., Results: Between February 2023 and September 2023, 42 patients were enrolled at five Danish hospitals. All patients received pembrolizumab and underwent surgery, except one patient who refused to undergo surgery. Surgery was performed a median of 32 days after pembrolizumab treatment. Twenty surgical complications were observed in 16 of 41 patients (39%), three of which were above Clavien-Dindo grade 2. Two were grade 3b, and one was a surgery-related grade 5 gastric ulcer perforation. Three adverse events were grade 3. No grade 4 or 5 adverse events were reported. Of the evaluable patients, 46% (19/41) achieved a pathological complete response, while 61% had a major pathological response., Conclusion: In conclusion, neoadjuvant single-cycle pembrolizumab was well tolerated and effective in patients with localized dMMR colon cancer. Thus, the inclusion of patients was continued until 85 patients., Competing Interests: Potential Conflicts of Interest: T.F. Justesen: Travel/Accommodations/Expenses/Lecture: AngioDynamics. P.C. Petersen: Consulting/Advisory Role: Takeda; Travel/Accommodations/Expenses: SERVIER. K.J. Emmertsen: Travel/Accommodations/Expenses: Johnson and Johnson. L.Ø. Poulsen: Travel/Accommodations/Expenses: Takeda, MSD. C. Qvortrup: Consulting/Advisory Role: Meck KGaA; Travel/Accommodations/Expenses: Roche, SERVIER, Merck KGaA, Pierre Fabre. The authors of this study, who are not mentioned above, declare no potential conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to investigate the association of co-medication with metformin, a statin, or beta blocker with survival in patients with primary ovarian cancer., Methods: Individual data from three phase III, randomized controlled trials (AGO-OVAR 11, AGO-OVAR 12, and AGO-OVAR 16) and one phase II trial (AGO-OVAR 15) were pooled and analyzed. Patients were classified as ever user if the specific co-medication was documented at least once during the trial, and were compared with never users as controls. Association of co-medications and outcomes were adjusted for potential confounders (age, International Federation of Gynecology and Obstetrics stage, histology, residual disease after surgery, Eastern Cooperative Oncology Group (ECOG) performance status, body mass index, Charlson Comorbidity Index, and assigned treatment within the trial) in multivariate Cox regression analyses., Results: Overall, n=2857 patients were included. Ever users were: 100 patients received metformin (3.5%), 226 patients received statins (7.9%), and 475 (16.6%) patients received beta blockers (n=391 selective beta blockers; 84 non-selective beta blockers) as co-medication. There were no significant differences regarding the baseline characteristics except that ever users were significantly older, more obese, and had more comorbidities, according to the Charlson Comorbidity Index, compared with controls. Multivariate analyses for progression free survival and overall survival revealed neither a significant impact of metformin on survival (progression free survival hazard ratio (HR) 0.94, 95% confidence interval CI 0.69 to 1.29, p=0.7; overall survival HR 0.82, 95% CI 0.58 to 1.17, p=0.28) nor for statins (progression free survival HR 0.98, 95% CI 0.82 to 1.18, p=0.87; overall survival HR 0.91, 95% CI 0.74 to 1.12, p=0.37). In contrast, ever users of selective beta blockers had a significantly higher risk for recurrence and death (progression free survival HR 1.22, 95% CI 1.05 to 1.41, p=0.009; overall survival HR 1.25 95% CI 1.06 to 1.47, p=0.009)., Conclusions: In this analysis, co-medication with metformin or statins had no significant impact on survival in patients with primary ovarian cancer. In contrast, co-medication with a beta blocker was associated with worse survival. However, whether this observation is related to the underlying condition rather than a direct negative impact on tumor biology remains unclear., Competing Interests: Competing interests: DD: honoraria: AstraZeneca, GSK, Intuitive, KLS Martin, Merck Sharp & Dohme (MSD); travel/accommodation/expenses: AstraZeneca; Data Safety Monitoring Board/Advisory Board: AstraZeneca, Eisai, GSK, KLS Martin, MSD, PharmaMar, Seagen. FH: personal fees and non-financial support: AstraZeneca, Roche, Tesaro, GSK, Clovis; personal fees: Zailabs and PharmaMar, outside the submitted work. JF: honoraria: Medupdate, Decision Resources, Simon-Kucher and Partners, Juniper, Bionest Partner, Vox Bio, Axiam Healthcare Strategies, Prosapient, Lilly, MedPartners; research funding: Roche Pharma AG, GSK/Tesaro; travel/accommodation/expenses: Roche Pharma AG. PH: grants, personal fees and non-financial support: Astra Zeneca, GSK; grants and personal fees: Roche, MSD, Clovis, Immunogen; personal fees: Sotio, Stryker, Zai Lab, Mersana, Miltenyi; grants: Boehringer lngelheim, Medac, Genmab, Deutsche Krebshilfe, Deutsche Forschungsgemeinschaft, outside the submitted work. PW: Advisory Board Member and received honoraria: Amgen, AstraZeneca, MSD, Novartis, Pfizer, Lilly, Roche Pharma, Eisai, Clovis, GSK, Daiichi Sankyo. MRM: honoraria: Astra Zeneca, Eisai, Genmab, GSK, Mersana, Takeda, Zailab; travel/accommodation/expenses: AstraZeneca, GSK, Takeda; Advisory Board: Allarity Therapeutics, Astra Zeneca, Biontech, Daiichi-Sankyo, Eisai, Genmab, GSK, lmmunogen, Incyte, Merck/MSD, Mersana, Regeneron, Zailab; Chairman (2020-2022) of the European Network of Gynaecological Oncology Trials group; Vice-President of the European Society of Gynaecological Oncology; Faculty member of the European Society of Medical Oncology; Scientific Chair of the International Gynecologic Cancer Society; stock options: Karyopharm Therapeutics, Sera Prognostics. IRC: grants/contracts: Astra Zeneca, Clovis, GSK, Mersana, BMS, MSD; honoraria: Astra Zeneca, Clovis, GSK, Mersana, BMS, MSD, Roche, PharmaMar, Seagen, ESAI, Novartis; travel/accommodation/expenses: Roche, GSK, Astra Zeneca, PharmaMar, MSD; Data Safety Monitoring Board/Advisory Board: Clovis, Deciphera, AdaptImmune, Sutro, Immunogen. GS: grants: MSD Italia S.r.l; consulting fees: Tesaro Bio Italy S.r.l, Johnson & Johnson; payment for expert testimony: Clovis Oncology Italia S.r.l; NC: grants: GSK, Astrazeneca; consulting fees: AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, Roche; honoraria: AstraZeneca, Novartis, Clovis Oncology,GSK, MSD/Merck; Data Safety Monitoring Board/Advisory Board: AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, Roche. AO: Grants to institution: AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc., Eisai Ltd, F. Hoffmann-La Roche Ltd, Regeneron Pharmaceuticals, lmmunogen Inc, Merck, Sharp & Dohme de Esparsia SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; consulting fees and honoraria: AstraZeneca, Clovis Oncology, Deciphera, Genmab, GSK, lmmunogen, Mersana Therapeutics, PharmaMar, MSD de Esparia SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Sattucklabs, Itheos, Eisai; travel/accommodation/expenses: AstraZeneca, PharmaMar, Roche; Data Safety Monitoring Board/Advisory Board: AstraZeneca, Clovis Oncology, Deciphera, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, MSD de Esparia SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Sattucklabs, Itheos, Eisai; JS: study funding to institution: GSK, AstraZeneca, MSD, Clovis, Tesaro; consulting fees: GSK, Astra Zeneca, Tesaro, MSD, Elisei, Clovis, Riemser, Roche; travel/accomodation/expenses: Roche; Data Safety Monitoring Board/Advisory Board: GSK, PharmaMar, Novocure, Astra Zeneca, Clovis, GSK, Tesaro; ESGO Faculty; NOGGO President; PARSGO President. KL: grants: GSK; honoraria: Eisai; Data Safety Monitoring Board/Advisory Board: Eisai, MSD, Nycode, Astra Zeneca, GSK. CL: honoraria: IMSD, GSK, Eisai, Clovis Oncology; travel/accommodation/expenses: MSD, GSK; Data Safety Monitoring Board/Advisory Board: GSK. ME: stock/stock options: GSK. AdB: honoraria: Zodiac, AMGEN, GSK/Tesaro; Data Safety Monitoring Board/Advisory Board: AstraZeneca/MSD, AMGEN, Pfizer, GSK/Tesaro. All other authors declare no competing interests., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Heart failure (HF) is considered a multifaceted and life-threatening syndrome characterized by high symptom-burden and significant mortality., Objectives: To describe the symptom-burden in patients with HF and identify their palliative care needs. In this respect, symptom burden related to sex, age and classification of HF using New York Heart Association Functional Classification (NYHA) were analyzed., Methods: A cross-sectional questionnaire survey included adult HF patients according to NYHA II, III, and IV. Palliative care needs were assessed using validated patient reported outcomes measures; SF-36v1, HeartQoL, EORTC- QLQ-C15-PAL, MFI-20 and HADS. Patients were recruited from the Department of Cardiology, North Zealand Hospital, Denmark., Results: In total, 314 patients (79%) completed the questionnaire (233 men). Mean age = 74 years (range 35-94 years). In all, 42% had NYHA III or IV and 53% self-rated their health to be fair or poor. In all, 19% NYHA II and 67% NYHA III/IV patients had ≥4 severe palliative symptoms according to EORTC-QLQ-C15-PAL. In addition, NYHA III/IV had a mean of 8.9 symptoms and a mean of 5.4 severe symptoms. Women, older patients, and those with NYHA III/IV had worse outcomes regarding health-related quality of life, functional capacity, and symptom burden., Conclusions: Patients with HF have a high prevalence of symptoms and, thus, potential palliative care needs. Predominantly, women, older patients, and those with higher severity of disease have the highest symptom burden. PROMs can help cardiologists address the palliative care needs and systematic assessment may be a prerequisite to integrate symptom-modifying and palliative care interventions., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Shared  decision making in healthcare is a fundamental right for patients. Healthcare professionals' perception of their own abilities to enable shared decision making is crucial for implementing shared decision making within service. IcanSDM (I can shared decision making) is a brief measure to investigate healthcare professionals' perception of shared decision making approaches to their practices. It was developed in Canada with French and English versions, and recently translated into German. This study aims to adapt the IcanSDM measure for Danish-speaking healthcare professionals, and evaluate its psychometric properties., Methods: Cultural adaptation and translation based on Beaton et al.'s approach was applied. A forward translation by ten people and a backward translation by two people were performed. To assess comprehensibility, cognitive interviews were conducted with 24 healthcare professionals. Eighty healthcare professionals who were trained in shared decision making for either one hour (n = 65) or one day (n = 15) participated in the psychometric evaluation. The evaluation concerned acceptance, item characteristics, skewness, item difficulties, corrected item-total correlations, inter-item correlations, factorial structure, internal consistency, and responsiveness., Results: The forward and backward translation revealed few discrepancies, and participants understood the items well. The psychometric evaluation showed a high completion rate and acceptable item difficulties and discrimination values. Both the factor analysis and the internal consistency showed a 2-factor structure: 1) healthcare professionals' capacity to implement shared decision making; and 2) healthcare professionals' capacity to practise shared decision making. The IcanSDM&#95;Danish obtained a Cronbach's alpha coefficient of 0.74. The evaluation of responsiveness showed improvement, but was not statistically significant., Conclusion: The IcanSDM&#95;Danish has good cross-cultural validity and internal consistency, and a 2-factor structure. The IcanSDM&#95;Danish is capable of providing reliable and valid measurement when evaluating constructed knowledge about shared decision making, and may be able to support the implementation of shared decision making training and evaluation of its impact., Competing Interests: Declarations Ethics approval and consent to participate The participants, all of whom were HCPs were informed that participation in the study was voluntary and that they could decline to participate by not completing the questionnaires. Due to Danish law, this type of study, do not need any ethical approval (https://www.retsinformation.dk/eli/lta/2023/1776). The study was conducted in accordance with the Helsinki Declaration and approved by the Danish Data Protection Agency (reference number: 1–16-02–284-23). Informed consent was obtained from all participants. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: Real-world data evaluating how approvals of novel treatment regimens for ovarian cancer have impacted the treatment paradigm, including first-line maintenance, are lacking. This analysis aimed to describe treatment patterns for advanced epithelial ovarian cancer in Europe and the USA in the first-line maintenance setting. Patient characteristics, biomarker testing rates, and drivers of treatment choice were also evaluated., Methods: A retrospective chart review study of electronic medical records in Europe and the USA was conducted for patients diagnosed with epithelial ovarian cancer (June 1, 2017-May 31, 2020), in line with Healthcare Market Research guidelines. Eligible physicians extracted data from electronic medical records by completing standardized patient record forms, including questions on patient involvement in treatment decisions. Patients with advanced (stage III/IV) disease were stratified by country and diagnosis date to provide information on treatment patterns., Results: Patient record forms for 7072 patients with epithelial ovarian cancer were completed by 416 physicians; 5386 patients had stage III/IV ovarian cancer. Over time, the percentage of patients who were tested for BRCA mutations or homologous recombination deficiency increased. Patient preference was documented as a reason for treatment selection in approximately one-sixth of cases in the first-line adjuvant and first-line maintenance settings. The use of first-line maintenance poly(ADP-ribose) polymerase inhibitor monotherapy increased over time, while the use of vascular endothelial growth factor inhibitor monotherapy decreased., Conclusions: This real-world study showed that treatment patterns for advanced epithelial ovarian cancer varied by country. Rates of physician-reported patient involvement in treatment decisions in the first-line adjuvant and maintenance treatment settings for ovarian cancer were low, highlighting an unmet need for initiatives to improve patient involvement in shared decision-making regarding maintenance therapy selection., Competing Interests: Competing interests: The authors disclose the following potential conflicts of interest: KNM: Institutional research grant: Angle PLC; Consulting fees: Fujirebio Diagnostics Inc; Advisory fees: GSK. MRM: Advisory board fees: Allarity Therapeutics, AstraZeneca, Biocad, BioNTech, Boehringer Ingelheim, Clovis, Daiichi-Sankyo, Eisai, Genmab, GSK, ImmunoGen, Incyte, Karyopharm, Merck/MSD, Mersana, Novartis, Regeneron, Roche, Seagen, Takeda, Tesaro, Zailab; membership on the board of directors or stockholder/shareholder: Karyopharm Therapeutics, Sera Prognostics; Institutional research grants: Allarity, Apexigen, AstraZeneca, Boehringer Ingelheim, Clovis, GSK, Novartis, Tesaro, Ultimovacs; Trial chair: AstraZeneca, Boehringer Ingelheim, Deciphera, Daiichi-Sankyo, GSK, Merck, Mersana, NuvationBio, Tesaro. SP: Honoraria: AstraZeneca, GSK, MSD, Roche; Research funding: AstraZeneca, GSK, MSD, Pfizer, Roche. CG: Honoraria/consultancy fees: AstraZeneca, Chugai, Clovis, Cor2Ed, Eisai, GSK, MSD, Peer Voice, Takeda; Research funding: Aprea, Artios, AstraZeneca, BerGen Bio, GSK, Medannexin, MSD, Novartis, NuCana; Issued/pending patents related to predicting treatment response in ovarian cancer. DL: Grants or contracts: Alkermes, AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, ImmunoGen, Incyte, MSD, Novartis, Pharma&, Pharmamar, Roche, Seagen; Consulting fees: AstraZeneca, Clovis Oncology, Corcept, Daiichi Sankyo, Genmab, GSK, ImmunoGen, MSD, Novartis, Novocure, Oncoinvest, Seagen, Sutro; Honoraria: AstraZeneca, Corcept, Genmab, GSK, ImmunoGen, MSD, Seagen; Support for attending meetings and/or travel: AstraZeneca, GSK, Menarini, MSD; Participation on a data safety monitoring board or advisory board: AstraZeneca, Clovis Oncology, Corcept, Daiichi Sankyo, Genmab, GSK, ImmunoGen, MSD, Novocure, Oncoinvest, Seagen, Sutro; Leadership or fiduciary roles: ENGOT, GCIG, MITO. BJM: Consulting fees: Acrivon, Adaptimune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Eisai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Iovance, Karyopharm, Laekna, MacroGenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, Teasro/GSK, US Oncology Research, VBL, Verastem, Zentalis; Speakers’ bureau honoraria: AstraZeneca, Eisai, Myriad, Roche/Genentech, Tesaro/GSK. JS: Grants or contracts: GSK, Roche; Consulting fees: Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Merck Sharp & Dohme, MSD, Novartis, Oncoinvent, Pfizer/Merck, PharmaMar, Roche; Honoraria fees: AstraZeneca, Clovis, Eisai, MSD, PharmaMar, Roche, Tesaro/GSK; Support for attending meetings: AstraZeneca, PharmaMar, Roche, Tesaro/GSK. JMS: Employee of GSK. ND'E: Employee of Genactis (the company that was contracted to perform the statistical analyses). AG-M: Fees for different educational or advisory-related activities: Alkermes, Amgen, AstraZeneca, Clovis, Eisai, Genmab, GSK, Hedera Dx, Immunogen, Illumina, Karyopharm, Macrogenics, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Regeneron, Roche, Seagen, Sotio, Sutro, Takeda, Tubulis., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Introduction: Nasopharyngeal carcinoma (NPC) is a rare disease and most studies have therefore been conducted in endemic areas. The aim of this study was to describe epidemiology and treatment outcomes of NPC in a population-based, non-endemic setting., Material and Methods: Patients with NPC diagnosed in Denmark from 2000 to 2018 were identified in the Danish Head and Neck Cancer Study Group (DAHANCA) database. Clinical records were reviewed to obtain missing data and confirm outcome, histological subtypes, Epstein-Barr virus (EBV)-status, prognostic factors, and treatment., Results: NPC was identified in 394 patients corresponding to age-standardized incidence rates of 0.5 and 0.2 per 100,000 in men and women, respectively. The 5-year overall (OS) and disease-specific survival (DSS) were 56 and 66%. In multivariate analysis, stage, smoking, and histology affected both OS and DSS, as patients with undifferentiated carcinomas had superior outcomes. Tumor EBV-status was determined in 221 patients, of whom 160 (72%) tested positive. EBV-positivity was associated with an improved OS in univariate analysis, but not after adjustment for relevant clinical factors., Interpretation: NPC is a rare malignancy in Denmark, and three in four patients have EBV-associated tumors. Tumor histology, smoking status, and stage, but not EBV-status, had independent prognostic impact on survival.

Competing Interests: Competing interests: None declared.

Background and Objective: The use and duration of androgen deprivation therapy (ADT) with postoperative radiotherapy (RT) have been uncertain. RADICALS-HD compared adding no ("None"), 6-months ("Short"), or 24-mo ("Long") ADT to study efficacy in the long term., Methods: Participants with prostate cancer were indicated for postoperative RT and agreed randomisation between all durations. ADT was allocated for 0, 6, or 24 mo. The primary outcome measure (OM) was metastasis-free survival (MFS). The secondary OMs included freedom from distant metastasis, overall survival, and initiation of nonprotocol ADT. Sample size was determined by two-way comparisons. Analyses followed standard time-to-event approaches and intention-to-treat principles., Key Findings and Limitations: Between 2007 and 2015, 492 participants were randomised one of three groups: 166 None, 164 Short, and 162 Long. The median age at randomisation was 66 yr; Gleason scores at surgery were as follows: <7 = 64 (13%), 3+4 = 229 (47%), 4+3 = 127 (26%), and 8+ = 72 (15%); T3b was 112 (23%); and T4 was 5 (1%). The median follow-up was 9.0 yr and, with MFS events reported for 89 participants (32 None, 31 Short, and 26 Long), there was no evidence of difference in MFS overall (logrank p = 0.98), and, for Long versus None, hazard ratio = 0.948 (95% confidence interval 0.54-1.68). After 10 yr, 80% None, 77% Short, and 81% Long patients were alive without metastatic disease. The three-way randomisation was not powered to conventional levels for assessment, yet provides a fair comparison., Conclusions and Clinical Implications: Long-term outcomes after radical prostatectomy are usually favourable. In those indicated for postoperative RT and considered suitable for no, short-term, or long-term ADT, there was no evidence of improvement with addition of ADT. Future research should focus on patients at a higher risk of metastases in whom improvements are required more urgently., (Copyright © 2024. Published by Elsevier B.V.)

Discovery of cancer risk variants in the sequence of the germline genome can shed light on carcinogenesis. Here we describe gene burden association analyses, aggregating rare missense and loss of function variants, at 22 cancer sites, including 130,991 cancer cases and 733,486 controls from Iceland, Norway and the United Kingdom. We identified four genes associated with increased cancer risk; the pro-apoptotic BIK for prostate cancer, the autophagy involved ATG12 for colorectal cancer, TG for thyroid cancer and CMTR2 for both lung cancer and cutaneous melanoma. Further, we found genes with rare variants that associate with decreased risk of cancer; AURKB for any cancer, irrespective of site, and PPP1R15A for breast cancer, suggesting that inhibition of PPP1R15A may be a preventive strategy for breast cancer. Our findings pinpoint several new cancer risk genes and emphasize autophagy, apoptosis and cell stress response as a focus point for developing new therapeutics., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The phase III PRIMA/ENGOT-OV26/GOG-3012 trial met its primary endpoint. Niraparib first-line maintenance significantly prolonged progression-free survival (PFS) among patients with newly diagnosed advanced ovarian cancer that responded to first-line platinum-based chemotherapy, regardless of homologous recombination deficiency (HRD) status. Final overall survival (OS) results are reported., Patients and Methods: Patients were randomized 2:1 to niraparib or placebo, stratified by response to first-line treatment, receipt of neoadjuvant chemotherapy, and tumor HRD status. After reaching 60% target maturity, OS was evaluated via a stratified log-rank test using randomization stratification factors and summarized using Kaplan-Meier methodology. OS testing was hierarchical [overall population first, then the homologous recombination-deficient (HRd) population]. Other secondary outcomes and long-term safety were assessed; an updated, ad hoc analysis of investigator-assessed PFS was also conducted (cut-off date, 8 April 2024)., Results: The median follow-up was 73.9 months. In the overall population, the OS hazard ratio was 1.01 [95% confidence interval (CI) 0.84-1.23; P = 0.8834] for niraparib (n = 487) versus placebo (n = 246). In the HRd (n = 373) and homologous recombination-proficient (n = 249) populations, the OS hazard ratios were 0.95 (95% CI 0.70-1.29) and 0.93 (95% CI 0.69-1.26), respectively. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 11.7% and 15.8% of niraparib patients and 37.8% and 48.4% of placebo patients in the overall and HRd populations, respectively. The 5-year PFS rate numerically favored niraparib in the overall (niraparib, 22%; placebo, 12%) and HRd populations (niraparib, 35%; placebo, 16%). Myelodysplastic syndromes/acute myeloid leukemia incidence was <2.5% (niraparib, 2.3%; placebo, 1.6%). No new safety signals were observed., Conclusions: In patients with newly diagnosed advanced ovarian cancer at high risk of recurrence, there was no difference in OS between treatment arms. In the HRd population, patients alive at 5 years were two times as likely to be progression free with niraparib treatment than placebo. Long-term safety remained consistent with the established niraparib safety profile., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Over the past 25 years, global opioid consumption has increased. Denmark ranks fifth in opioid use globally, exceeding other Scandinavian countries. Postsurgical pain is a common reason for opioid prescriptions, but opioid use patterns after patient discharge from the hospital are unclear. This study examines trends in opioid prescription among Danish surgical patients over a year., Methods: This register-based cohort study will use data from Danish governmental databases related to patients undergoing the 10 most frequent surgical procedures in 2018, excluding cancer-related and minor procedures. The primary outcome will be the dispensed postoperative opioid prescriptions at retail pharmacies over four quarters. Secondary analyses will include associations with sex, age, education attainment, and oral morphine equivalent quotient. Surgical treatments and diagnoses will be identified using NOMESCO procedure codes and ICD-10 codes. Opioids will be identified by ATC codes N02A and R05DA04. Subjects will be classified as preoperative opioid consumers or non-opioid consumers based on opioid prescriptions redeemed in the 6 months before surgery., Discussion: The study will use extensive national register-based data, ensuring consistent data collection and enhancing the generalizability of the findings to similar healthcare systems. The study may identify high-risk populations for long-term opioids and provide information to support opioid prescribing guidelines and public health policies., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Introduction: Older patients with gastroesophageal (GE) cancer are at increased risk of low treatment tolerability and poor outcome. Dose reduced chemotherapy has been shown to improve tolerability without compromising efficacy in advanced GE cancer. However, the impact of reduced dose preoperative chemotherapy in the curative setting of older patients is unknown. The primary aim of this study was to investigate if dose reduction during preoperative chemotherapy impacts survival in older patients aged≥70 years with resectable GE cancer., Materials and Methods: This cohort study included consecutive patients referred to perioperative chemotherapy treated from November 2016 until October 2021. The primary endpoint was overall survival (OS) estimated by Kaplan-Meier analysis. The log-rank test was used to compare survival rates. A multivariate analysis was made to control for potentially interacting covariates., Results: A total of 548 patients (age ≥ 70, 179; age < 70, 369) were included. Fewer older compared to younger patients had Eastern Cooperative Oncology Group Performance Status 0 at baseline (50 % vs 63 %, p = 0.007). Preoperative chemotherapy was more often initiated at reduced dose in older patients compared to younger (37 % vs 14 %, p < 0.001). Older patients who did not receive a reduce dose in the second or subsequent cycles of preoperative chemotherapy were less likely to complete preoperative chemotherapy when compared to the younger patients (75 % vs 85 %, p = 0.03). Dose reduction in the second or subsequent preoperative chemotherapy cycles was associated with significantly better OS for the older patient population (HR = 0.54, 95 % CI: 1.2-2.9, p = 0.006) but not for the younger (HR = 0.97, 95 % CI: 0.75-1.4, p = 0.83). Dose reduction in the second or subsequent preoperative chemotherapy cycles was associated with lower mortality risk in the multivariate analysis for the older patients (HR = 0.56, 95 % CI: 0.33-0.97, p = 0.04)., Discussion: Dose reduction in the second or subsequent preoperative chemotherapy cycles seems safe and feasible in older patients without compromising survival and may result in a benefit in OS. This finding should be validated in an independent cohort or a randomized trial., Competing Interests: Declaration of Competing Interest Josephine Skjoldbirk Andersen: None. Kristian Egebjerg: None. Michael Patrick Achiam: None. Camilla Qvortrup: Grants from Servier, personal fees from Pierre Fabre. Lene Bæksgaard: None. Cecilia M. Lund: None. Morten Mau-Sørensen: Morten Mau-Sørensen has served on advisory boards for Astellas, MSD/Merck, AstraZeneca, and BMS., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Breast cancer patients have an increased risk of cardiometabolic disease and for many patients, adjuvant therapy causes an altered lipid profile, insulin resistance and inflammation. Previous follow-up studies are inconclusive regarding the duration of therapy-induced inflammation. We examined the acute and persistent changes of adjuvant chemotherapy on inflammatory and metabolic health markers in breast cancer patients., Methods: Plasma levels of IL-6, IL-8, IL-10, IFN-γ, TNF-α, high-sensitivity C-reactive protein (hsCRP) and metabolic health parameters were analyzed before, shortly after and every six months up to two years after adjuvant chemotherapy treatment in 51 postmenopausal early breast cancer (EBC) patients, as well as in 41 healthy age- and BMI-matched controls. A target-specific multiplex assay was applied for cytokine measurements., Results: Before initiation of adjuvant therapy, plasma IL-8 levels were higher in EBC patients (31%, p = 0.0001). Also, a larger proportion of the patients had a hsCRP level above 2 mg/L (41%) compared to the controls (17%, Χ 2  = 5.15, p = 0.023). Plasma levels of all five cytokines, but not hsCRP, were significantly increased after compared to before adjuvant chemotherapy (15-48% increase; all p ≤ 0.05). Already six months after ending chemotherapy treatment, all plasma cytokine levels were significantly reduced and close to pre-chemotherapy levels. Adjuvant chemotherapy caused a worsened lipid profile (increased triglycerides, lower HDL levels), insulin resistance and increased plasma insulin levels that remained high during the first year after chemotherapy., Conclusion: Postmenopausal women with EBC have temporarily increased plasma levels of pro-inflammatory cytokines after adjuvant chemotherapy. Although transient, the therapy-induced increase in plasma cytokine levels, together with dyslipidemia and insulin resistance, may contribute to cardiometabolic risk in breast cancer patients treated with adjuvant chemotherapy., Trial Registration: The clinical trial (registration number NCT03784651) was registered on www., Clinicaltrials: gov on 24 December 2018., (© 2024. The Author(s).)

Background/objectives: Long-term consequences of opioid consumption, such as misuse, have been a major concern in patients with chronic non-cancer pain. Potentially opioid misuse may also be a consequence in patients with cancer in opioid treatment which encouraged us to undertake this systematic review assessing the frequency of opioid misuse in this population., Materials/methods: The search strategy comprised words related to cancer, opioid misuse, and frequency. PubMed, Embase, PsycInfo, and Cinahl were searched from inception to July 2023. Prospective studies were selected and analysed regarding frequency, study characteristics, and quality. A meta-analysis was possible to carry out for a sub-group (opioid misuse risk)., Results: From 585 abstracts screened, six articles were included. Only prevalence data were found. The prevalence of opioid misuse ranged from 5.7% to 84%, while the prevalence of opioid misuse risk varied from 2.4% to 35.4%. The pooled prevalence of opioid misuse risk was 12.3% (95% CI: 0.8-36.3; I 2  = 98.4%, 95% CI: 97.2-99.1). The studies differed regarding, e.g., methods, misuse definitions, and assessment instruments., Conclusions: Few studies were identified and large differences in prevalence for opioid misuse and opioid misuse risk were observed. Methodological disparities and the studies quality underscore the importance of improved studies in the future., (© 2024. The Author(s).)

Background/aim: The emergence of novel DNA damage repair (DDR) pathways in molecular-target therapy drugs (MTTD) has shown promising outcomes in treating patients with metastatic castration-resistant prostate cancer (mCRPC). About 25% of mCRPC patients have actionable deleterious aberrations in DDR genes, primarily in the homologous recombination (HR) pathway. However, the response rate in patients with BRCA1/2 or mutations in HRR-related genes is only 45%-55%, when exposed to poly ADP ribose polymerase (PARP) inhibitor-based therapy (PARPi). A frequent characteristic feature of prostate cancer (PC) is the occurrence of genomic rearrangement that affects the transmembrane protease serine 2 (TMPRSS2) and E26 transformation-specific (ETS)- transcription factor-related gene (ERG)., Materials and Methods: In this study, a total of 114 patients with mCRPC had their RNA and DNA sequenced using next-generation sequencing., Results: Based on their genetic profile of deleterious gene alterations of BRCA1/2 or ATM, six patients were selected for PARPi. Patients with TMPRSS2:ERG gene fusion and homozygous alteration in ATM or BRCA2 (n=2) or heterozygous alterations (BRCA1 or BRCA2) and lack of TMPRSS2:ERG gene fusion (n=2) did not show clinical benefit from PARPi (treatment duration <16 weeks). In contrast, patients (n=2) without TMPRSS2:ERG gene fusion and homozygous deleterious alterations in ATM or BRCA2 all had clinical benefit from PARPi (treatment duration ≥16 weeks)., Conclusion: The TMPRSS2:ERG transcript product might be used as a PARPi resistance biomarker., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

PURPOSESocial characteristics, including cohabitation/marital status and socioeconomic position (SEP)-education level, employment status, and income-influence breast cancer prognosis. We investigated the impact of these social characteristics on adherence to adjuvant endocrine therapy (AET) from treatment initiation to 5 years after diagnosis.METHODSWe assembled a nationwide, population-based cohort of premenopausal women diagnosed in Denmark with stage I-III, estrogen receptor-positive breast cancer during 2002-2011. We ascertained prediagnostic social characteristics from national registries. AET adherence was based on information from the Danish Breast Cancer Group and operationalized as (1) adherence trajectories (from group-based trajectory modeling) and (2) early discontinuation. We computed odds ratios (ORs) and associated 95% CI to estimate the association of cohabitation and SEP with AET adherence using multinomial and logistic regression models adjusted according to directed acyclic graphs.RESULTSAmong 4,353 patients, we identified three adherence trajectories-high adherence (57%), slow decline (36%), and rapid decline (6.9%). Compared with cohabiting women, those living alone had higher ORs of slow (1.26 [95% CI, 1.08 to 1.46]) or rapid decline (1.66 [95% CI, 1.27 to 2.18]) versus high adherence. The corresponding ORs for women not working versus employed women were 1.22 (95% CI, 1.02 to 1.45) and 1.76 (95% CI, 1.30 to 2.38). For early discontinuation (17%), the ORs were 1.48 (95% CI, 1.23 to 1.78) for living alone and 1.44 (95% CI, 1.17 to 1.78) for women not working.CONCLUSIONAdherence to AET was lower among women living alone or unemployed than cohabiting or employed women, respectively. These women may benefit from support programs to enhance AET adherence.

Background: Most patients with advanced anaplastic lymphoma kinase ( ALK )-rearranged ( ALK +) non-small cell lung cancer (NSCLC) experience prolonged response to second-generation (2G) ALK-tyrosine kinase inhibitors (TKIs). Herein, we present a case of metastatic ALK + NSCLC rapidly progressing on first-line treatment due to de novo amplification of the mesenchymal-epithelial transition factor ( MET ) gene, which is a still elusive and underrecognized mechanism of primary resistance to ALK-TKIs., Case Description: A 43-year-old, female diagnosed with T4N3M1c NSCLC harboring the echinoderm microtubule-associated protein-like 4 ( EML4 ) -ALK fusion variant 1 ( EML4-ALK v.1) and TP53 co-mutation, displayed only mixed response after three months and highly symptomatic progression after 6 months of first-line brigatinib treatment. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis on re-biopsies from a new liver metastasis revealed overexpression of MET receptor (3+ in 80% of tumor cells) and heterogeneously increased MET gene copy number (CN) in tumor cells, including 20% with MET clusters (corresponds to ≥15 gene copies, thus exact CN uncountable by FISH) and the other 80% with median MET CN of 8.3, both changes indicating high-level MET- amplification. DNA and RNA next-generation sequencing (NGS) displayed preserved ALK fusion and TP53 co-mutation, but no additional genomic alterations, nor MET- amplification. Therefore, we retrospectively investigated the diagnostic biopsy from the primary tumor in the left lung with IHC and FISH revealing the presence of increased MET receptor expression (2+ in 100% of tumor cells) and MET- amplification (median MET CN of 6.1), which otherwise was not detected by NGS. Thus, given the well-documented efficacy of alectinib towards EML4-ALK v.1, combined second-line treatment with alectinib and the MET-TKI, crizotinib, was implemented resulting in very pronounced objective response, significantly improved quality of life, and no adverse events so far during the ongoing treatment (6 months)., Conclusions: The combination of alectinib and crizotinib may be a feasible and effective treatment for ALK + NSCLC with de novo amplification. The latter may represent a mechanism of intrinsic ALK-TKI resistance and its recognition by FISH, in NGS-negative cases, may be considered before initiating first-line treatment. This recognition is clinically important as combined therapy with ALK-TKI and MET-inhibitor should be the preferred first-line treatment.MET- amplification. The latter may represent a mechanism of intrinsic ALK-TKI resistance and its recognition by FISH, in NGS-negative cases, may be considered before initiating first-line treatment. This recognition is clinically important as combined therapy with ALK-TKI and MET-inhibitor should be the preferred first-line treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-439/coif). E.M.U. reports research grants from AstraZeneca and Merck; speaker fees from Amgen, AstraZeneca, Janssen and Novartis; travel support related to participation in international scientific meeting from AstraZeneca and Roche; payment for participation in Advisory Board from AstraZeneca, Pfizer, Roche and Takeda. M.G. reports speaker fees from Amgen, AstraZeneca, Boehringer Ingelheim and ThermoFisher Scientific, and received research grants from Merck and Roche. J.B.S. received consulting fees from AstraZeneca, Bristol-Myers Squibb, Merck, Janssen, Roche; received honoraria for lectures from Bristol-Myers Squibb, Janssen; received support for attending meetings and/or travel from AstraZeneca, Janssen, Merck; and received payment for participation in Advisory Board from AstraZeneca, Bristol-Myers Squibb, Genmab, Janssen, Merck, Roche. E.S.R. received research grants from Sanofi and Takeda; reports honoraria for lectures from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Roche, Takeda; and received payment for participation in Advisory Board from Roche and Takeda. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Purpose: Breast cancer patients' need for social benefits may increase following taxane-based chemotherapy, due to long-lasting side effects. Specific single nucleotide polymorphisms (SNPs) may mediate such side effects. We investigated the association between SNPs related to taxane metabolism, transport, toxicity, or DNA and neural repair, and receipt of social benefits., Methods: From the Danish Breast Cancer Group, we identified premenopausal women diagnosed with stage I-III breast cancer during 2007-2011 and treated with docetaxel-based chemotherapy. We genotyped 21 SNPs from archived breast tumors using TaqMan assays. We ascertained social benefit payments from 1 year before to 5 years after diagnosis, using nationwide, administrative registry data. For each week, we categorized women as receiving health-related benefits (including sick leave and disability pension), labor market-related benefits (including unemployment benefits), or as being self-supporting. We computed rate ratios (RRs) of social benefit receipt for variant carriers (heterozygotes plus homozygotes) vs. non-carriers, using negative binominal regression with robust variance estimation., Results: Among 2430 women, 12% received health-related benefits before diagnosis, 80% at diagnosis, and ~ 24% 2 to 5 years after diagnosis. Labor market-related benefits were uncommon (3-6%). All RRs were near-null and/or imprecise., Conclusion: We found no clinically meaningful impact of the selected SNPs on social benefit receipt among premenopausal breast cancer survivors treated with docetaxel., (© 2024. The Author(s).)

Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, accompanied by chemotherapy and radiotherapy. Malignant cells escape surgical resection by migrating into the surrounding healthy brain tissue, where they give rise to the recurrent tumor. Based on gene expression, tumor cores can be subtyped into mesenchymal, proneural, and classical tumors, each being associated with differences in genetic alterations and cellular composition. In contrast, the adjacent brain parenchyma where infiltrating malignant cells escape surgical resection is less characterized in patients. Using spatial transcriptomics (n = 11), we show that malignant cells within proneural or mesenchymal tumor cores display spatially organized differences in gene expression, although such differences decrease within the infiltrated brain tissue. Malignant cells residing in infiltrated brain tissue have increased expression of genes related to neurodevelopmental pathways and glial cell differentiation. Our findings provide an updated view of the spatial landscape of glioblastomas and further our understanding of the malignant cells that infiltrate the healthy brain, providing new avenues for the targeted therapy of these cells after surgical resection., (© 2024. The Author(s).)

Background: Camonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-target anemia is the main drug-related toxicity typically manifesting after the period of dose-limiting toxicity evaluation. Thus, dose and schedule optimization requires extended follow-up to assess prolonged treatment effects., Methods: Long-term safety, tolerability, and antitumor efficacy of 3 camonsertib monotherapy dosing regimens were assessed in the TRESR study dose-optimization phase: 160 mg once daily (QD) 3 days on, 4 days off (160 3/4; the preliminary recommended Phase II dose [RP2D]) and two step-down groups of 120 mg QD 3/4 (120 3/4) and 160 mg QD 3/4, 2 weeks on, 1 week off (160 3/4, 2/1w). Safety endpoints included incidence of treatment-related adverse events (TRAEs), dose modifications, and transfusions. Efficacy endpoints included overall response rate, clinical benefit rate, progression-free survival, and circulating tumor DNA (ctDNA)-based molecular response rate., Results: The analysis included 119 patients: 160 3/4 (n = 67), 120 3/4 (n = 25), and 160 3/4, 2/1w (n = 27) treated up to 117.1 weeks as of the data cutoff. The risk of developing grade 3 anemia was significantly lower in the 160 3/4, 2/1w group compared with the preliminary RP2D group (hazard ratio = 0.23, 2-sided P = .02), translating to reduced transfusion and dose reduction requirements. The intermittent weekly schedule did not compromise antitumor activity., Conclusion: The 160 3/4, 2/1w dose was established as an optimized regimen for future camonsertib monotherapy studies offering a substantial reduction in the incidence of anemia without any compromise to efficacy., Clinical Trial Id: NCT04497116., (© The Author(s) 2024. Published by Oxford University Press.)

Objectives: In patients with epithelial ovarian cancer (EOC), the clinical efficacy of monotherapy with immune checkpoint inhibitors (ICIs) against PD-1/PD-L1 is modest. To enhance response rates to these immunotherapeutic agents and broaden the indications for their use, new approaches involving combinational therapy are needed. The immune regulator CD73 is a potential target, as it promotes tumor escape by producing immunosuppressive extracellular adenosine in the tumor microenvironment. Here, we present the results from the NSGO-OV-UMB1/ENGOT-OV-30 trial evaluating the activity of combining the anti-CD73 antibody oleclumab with the anti-PD-L1 checkpoint inhibitor durvalumab in patients with recurrent EOC., Methods: In this phase II open-label non-randomized study, patients with CD73-positive relapsed EOC were intravenously administered oleclumab (3000 mg, Q2W) and durvalumab (1500 mg, Q4W). The primary endpoint was disease control rate (DCR) at 16 weeks. The expression of PD-L1 and CD8 was assessed by immunohistochemistry of archival tumors., Results: This trial included 25 patients with a median age of 66 years (47-77 years). Twenty-two patients were evaluable for treatment activity analysis. The DCR was 27%, the median progression-free survival was 2.7 months (95% CI: 2.2-4.2) and the median overall survival was 8.4 months (95% CI: 5.0-13.4). Infiltration of CD8 + cells and PD-L1 expression on tumor cells were observed in partially overlapping sets of 74% of the tumor samples. Neither CD8- nor PD-L1-positivity were significantly associated with better DCR., Conclusions: Combined treatment with oleclumab and durvalumab was safe and demonstrated limited anti-tumor activity in patients with recurrent EOC., Competing Interests: Declaration of competing interest The authors declare the following financial interest / personal relationship which may be consider as potential competing interests: MRM reports receiving an institutional study grant and investigational medicinal product from AstraZeneca (no personal grants were received). JM reports having received consulting fee payments from GlaxoSmithKline, AstraZeneca and Eisai; receiving payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Eisai; and participation on a data safety monitoring board or advisory board of Eisai. KL reports receiving research funding from GlaxoSmithKline; receiving consulting fee payments from AstraZeneca, Merck Sharp and Dohme, Nykode, Eisai and GlaxoSmithKline; and being on the safety monitoring board of Karyopharm. AA reports participation on the advisory boards of GlaxoSmithKline and Merck Sharp and Dohme. LAA reports receiving grants or contracts from the Research Council of Norway. LCVT reports receiving personal fees for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Bayer and AstraZeneca; and receiving personal fee payments from Eisai for participating on a data safety monitoring board or Advisory Board. KM reports receiving speakers' honoraria from GlaxoSmithKline and AstraZeneca; receiving compensation for travel expenses from GlaxoSmithKline and AstraZeneca; participating in a trial-specific safety review committee for Kancera AB; and being the deputy medical director for NSGO-CTU. LB reports receiving speakers' honoraria from GlaxoSmithKline, and Merck Sharp and Dohme; having leadership roles in Onkologisk Forum between 2018 and 2022, and in the NSGO and NSGO-CTU since 2021; and receiving investigational medicinal product from AstraZeneca for a researcher-initiated trial. LT, JRH, RdPC, MW, HR and SNL report no personal conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Treatment options are limited for patients with previously treated metastatic colorectal cancer (mCRC). In the LEAP-017 study, we evaluate whether lenvatinib in combination with pembrolizumab improves outcomes compared with standard of care (SOC) in previously treated mismatch repair proficient or not microsatellite instability high (pMMR or not MSI-H) mCRC., Methods: In this international, multicenter, randomized, controlled, open-label, phase III study, eligible patients age 18 years and older with unresectable, pMMR or not MSI-H mCRC, that had progressed on or after, or could not tolerate, standard treatment, were randomly assigned 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 400 mg intravenously once every 6 weeks or investigator's choice of regorafenib or trifluridine/tipiracil (SOC). Randomization was stratified by presence or absence of liver metastases. The primary end point was overall survival (OS). LEAP-017 is registered at ClinicalTrials.gov (NCT04776148), and has completed recruitment., Results: Between April 8, 2021, and December 21, 2021, 480 patients were randomly assigned to lenvatinib plus pembrolizumab (n = 241) or SOC (n = 239). At final analysis (median follow-up of 18.6 months [IQR, 3.9]), median OS with lenvatinib plus pembrolizumab versus SOC was 9.8 versus 9.3 months (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02]; P = .0379; prespecified threshold P = .0214). Grade ≥3 treatment-related adverse events occurred in 58.4% (lenvatinib plus pembrolizumab) versus 42.1% (SOC) of patients. Two participants died due to treatment-related adverse events, both in the lenvatinib plus pembrolizumab arm., Conclusion: In patients with pMMR or not MSI-H mCRC that had progressed on previous therapy, there was no statistically significant improvement in OS after lenvatinib plus pembrolizumab treatment versus SOC. No new safety signals were observed.

Materials and Methods: This study included patients registered in the national Danish Breast Cancer Group (DBCG) database between 2001 and 2015, with locoregional LNM as well as a bilateral negative mammography, ultrasonography, and physical examination of the breasts. Overall survival (OS) and invasive disease-free survival (IDFS) were compared by treatment groups, ALND + RT (axillary lymph node dissection and radiotherapy) or ALND + MAST ± RT (axillary lymph node dissection, mastectomy with or without radiotherapy)., Results: In total, 56 patients were included in the study, of which 37 were treated by ALND + RT, 16 by ALND + MAST ± RT, and the remaining three patients receiving different treatments. The median follow-up for the 53 OBC patients sorted by treatment group was 12.2 years (interquartile range: 10.1 years; 15.3 years). There was no significant difference in OS or IDFS between the treatment groups, except for a subgroup of 46 (out of 53) patients without verified in situ lesions before treatment, where ALND + RT treatment showed an improved OS (log-rank p =0.05)., Conclusion: Treating OBC patients with ALND and radiotherapy resulted in a similar outcome as treatment with ALND and mastectomy. This supports omission of mastectomy in favor of radiotherapy of the breast in these patients., Competing Interests: Ann Søegaard Knoop reports a relationship with Novartis that includes consulting or advisory and funding grants; reports a relationship with Seagen, Inc., that includes consulting or advisory; reports a relationship with AstraZeneca that includes consulting or advisory, funding grants, and travel reimbursement; reports a relationship with Pfizer that includes consulting or advisory; reports a relationship with Roche that includes funding grants; and reports a relationship with Daiichi Sankyo, Inc., that includes consulting or advisory and funding grants. Anne-Vibeke Lænkholm reports a relationship with AstraZeneca that includes consulting or advisory and funding grants and reports a relationship with MSD Denmark that includes consulting or advisory. Tove Filtenborg Tvedskov reports a relationship with Roche that includes speaking and lecture fees; reports a relationship with Pfizer that includes speaking and lecture fees; and reports a relationship with MSD Denmark that includes travel reimbursement., (Copyright © 2024 Andreas Werner Nærum et al.)

Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with poor prognosis and limited treatment options. Immunotherapy shows potential for improved outcomes; however, real-world evidence on its use will take time to accumulate. This study examined patient characteristics, treatment patterns, overall survival (OS), and predictors of mortality among patients diagnosed with MPM in Denmark prior to the introduction of newer treatments., Methods: This historical cohort study based on routinely collected Danish National Registry data included adults newly diagnosed with MPM between 01 January 2011 and 31 May 2018. Summary statistics were used to describe patient characteristics and initial treatment. OS was estimated using Kaplan-Meier methods; Cox regression was used to compare patient mortality against the (age/sex-matched) general population and to investigate mortality predictors., Results: Overall, 880 patients were included; 44% had advanced MPM, 37% had non-advanced MPM, and 19% had unknown MPM stage. Median age at diagnosis was 71.9 years, and 82% of the patients were male. Within 180 days of diagnosis, no treatment was recorded for 215 patients (54%) with advanced MPM and 150 (46%) with non-advanced MPM. Median time-to-initial treatment (interquartile range) was 47 days (31-111) overall, 40 days (28-77) in patients with advanced MPM, and 53 days (35-121) with non-advanced MPM. Median OS was 13.7 months overall (non-advanced MPM: 18.0 months vs. advanced MPM: 10.0 months). Predictors of higher mortality were older age at diagnosis, histology, and advanced MPM stage., Interpretation: These findings provide a baseline upon which to evaluate MPM epidemiology as newer treatments are adopted in routine practice.

Background: Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 ( TP53 ) in endometrial cancer can integrate novel strategies for improved and individualized treatment that could impact patient outcomes. In an exploratory analysis of the phase III ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance monotherapy 80 mg in advanced/recurrent endometrial cancer, a pre-specified subgroup of patients with TP53 wild type (wt) endometrial cancer showed preliminary activity at long-term follow-up with a generally manageable safety profile (median progression-free survival 27.4 months vs 5.2 months placebo, HR=0.41)., Primary Objective: To evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent TP53 wt endometrial cancer., Study Hypothesis: Selinexor administered at 60 mg weekly as maintenance therapy will show manageable safety and maintain efficacy in patients with TP53 wt advanced/recurrent endometrial cancer after systemic therapy versus placebo., Trial Design: This is a prospective, multicenter, double-blind, placebo-controlled, randomized phase III study designed to evaluate the efficacy and safety of selinexor as a maintenance therapy in patients with advanced or recurrent TP53 wt endometrial cancer., Major Inclusion/exclusion Criteria: Eligible patients must have histologically confirmed endometrial cancer, TP53 wt confirmed by next-generation sequencing, completed at least 12 weeks of platinum-based therapy with or without immunotherapy, with confirmed partial response or complete response, and primary Stage IV disease or at first relapse., Primary Endpoint: The primary endpoint is investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the intent-to-treat population., Sample Size: A total of 220 patients will be enrolled., Estimated Dates for Completing Accrual and Presenting Results: Accrual is expected to be completed in 2024 with presentation of results in 2025., Trial Registration: NCT05611931., Competing Interests: Competing interests: IV reports consulting for Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Sanofi, Regeneron, Seagen, Sotio, Verastem Oncology, Zentalis. APF has received grants/research support from AstraZeneca, Pharmamar, GSK (paid to the institution); participation in a company-sponsored speaker’s bureau for AstraZeneca, MSD, Eisai, GSK, Clovis, Pharmamar, Pharma&; and honoraria or consultation fees from GSK, Clovis, AstraZeneca, Pharmamar, Roche, MSD, Ability Pharma. BJM has received honorarium and consulting fees from Acrivon, Adaptimmune, Agenus, Akeso Bio, Amgen, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna Health Care, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, VBL, Verastem, Zentalis; and speaker/consultant fees from AstraZeneca, Clovis, Easai, Merck, Roche/Genentech, TESARO/GSK. TH reports scientific advisory board participation: Aadi, AZ, Caris, Clovis, Corcept, Epsilogen, Eisai, Genentech, GSK, J&J, Merck, Seagen. GV reports grants or contracts from advisory boards of AZ, MSD, Clovis, GSK Pharmamar, Eisai. Consulting fees, honoraria, and support for attending meetings from advisory boards of AZ, MSD, Clovis, GSK, Pharmamar, Eisai. DC has nothing to disclose. NC reports fees for advisory board membership for AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Oncxerna, Pieris, Roche, Novocure; fees as an invited speaker for AstraZeneca, Clovis Oncology, GSK, MSD/Merck, Eisai; institutional research grants from AstraZeneca, Roche, GSK; non-remunerated activities as member of the ESMO Guidelines Steering Committee and chair of the Scientific Committee of ACTO (Alleanza contro il tumore Ovarico). BP reports grants, advisory board, and consultant fees; institutional PI for industry sponsored trials from Tesaro/GSK, AstraZeneca, Merck, Genetech/Roche, Celsion, Karyopharm, Mersana, Takeda Pharmaceuticals, Toray, Imab, Sutro, SeaGen, Clovis Oncology. Compensated advisory boards include Tesaro/GSK, AstraZeneca, Lily, Mersana, Onconova, Merck, Clovis Oncology, Eisai, Toray, Sutro, Deciphera, Imab, SeaGen, GOG Foundation. JS reports research funding: Institution: AZ, Clovis Oncology, Merck, Bayer, PharmaMar, Pfizer, Tesaro, MSD Oncology, Roche. Consulting/advisory boards: AZ, Clovis Oncology, PharmaMar, Merck, Pfizer, Tesaro, MSD Oncology, Lilly, Novocure, J&J, Roche, Ingress Health, Riemser, Sobi, GSK, Novartis; honoraria: AZ, Eisai, Clovis Oncology, Olympus Medical Systems, J&J, PharmaMar, Pfizer, Teva, Tesaro, MSD Oncology, GSK, Bayer. Travel, accommodation, expenses: AZ, Clovis Oncology, PharmaMar, Roche Pharma AG, Tesaro, MSD Oncology, Olympus. JK has nothing to disclose. JB reports participation on advisory boards for AstraZeneca, Clovis, Mersana, OncoC4, Immingen. Speaker's bureau for AstraZeneca, Merck. CP reports honoraria from Novartis, Astra Zeneca, Genesis, MSD Oncology, Servier, WinMedica; has received fees for consulting or advisory role from Amgen, Astellas, BioPharma, Roche Hellas, Astra Zeneca; and research funding from Roche Hellas, WinMedica, Servier. TvG has received grants/research supports (all paid to institution) from Amgen, AstraZeneca, Roche; advisory board (all paid to institution): AstraZeneca, BioNTech, Eisai, GSK, ImmunoGen, Incyte, Karyopharm, MSD, OncXerna, Seagen, Tubulis, Zentalis; participation in a company sponsored speaker’s bureau (all paid to institution): GSK, ImmunoGen, MSD. DR has received fees for advisory boards from Mersana, GlaxoSmithKline, AstraZeneca, ProfoundBio, Eisai, Immunogen. Grants/research supports paid to institution from GlaxoSmithKline, Lilly, Celsion, Mersana, Hookipa, Syros, AstraZeneca, Shattuck Labs, ProfoundBio, CanariaBio, Immunogen, Karyopharm. MMC has nothing to disclose. YA has received grants/research supports from AstraZeneca; honoraria or consultation fees from AstraZeneca; MSD, Eisai, GSK. Consulting or advisory role with AstraZeneca, Eisai, MSD, GSK, Pfizer. MRM has received grants/research supports from AstraZeneca (institution); Boehringer Ingelheim (institution); Pfizer (institution); Tesaro (institution); honoraria or consultation fees from honoraria: Advaxis, AstraZeneca, Cerulean Pharma, Clovis Oncology, Novocure, Pfizer, Roche, Tesaro; consulting or advisory role: AstraZeneca, BioCad, Cerulean Pharma, Clovis Oncology, Genmab, Karyopharm Therapeutics, Novocure, Pfizer, Tesaro; stock shareholder: Karyopharm Therapeutics, SeraCare; and leadership: Karyopharm Therapeutics. KL is an employee of Karyopharm Therapeutics. PK is an employee of Karyopharm Therapeutics. BS reports consulting or advisory roles for Genentech, Eisai, AstraZeneca, Karyopharm Therapeutics, Incyte, Clovis Oncology, Myriad Genetic Laboratories Inc., GlaxoSmithKline LLC, AbbVie Inc., Seagen Inc., Novocure Inc., Novartis, Immunogen, Agenus, Merck Sharp & Dohme, GOG Foundation. RLC has received grant/research support from AstraZeneca/MedImmune (institution), Clovis Oncology (institution), Merck (institution), Roche/Genentech (an immediate family member), Immunogen (institution), Mirati Therapeutics (institution), Amgen (institution), Pfizer (institution), Lilly (institution), Regeneron (institution); honoraria or consulting fees from Clovis Oncology, Genentech/Roche, AstraZeneca/MedImmune, Genmab, OncoMed, Immunogen, AbbVie, Agenus, Novocure, Merck, OncXerna Therapeutics, Alkermes, Gradalis, GlaxoSmithKline, Eisai, GOG Foundation, Karyopharm Therapeutics; stock shareholder from McKesson; and is employed by US Oncology. Leadership: Onxeo. Travel, accommodation, expenses: Merck, AstraZeneca/MedImmune, Array BioPharma, Clovis Oncology, Roche/Genentech, Research to Practice, GOG Foundation, Clovis Oncology, Sotio, Vaniam Group., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Molecular characterization of endometrial cancer is allowing for increased understanding of the natural history of tumors and paving a more solid pathway for novel therapies. It is becoming increasingly apparent that molecular classification is superior to histological classification in terms of reproducibility and prognostic discrimination. In particular, the Proactive Molecular Risk Classifier for Endometrial Cancer allows classification of endometrial cancer into groups very close to those determined by the Cancer Genome Atlas Research Network-that is, DNA polymerase epsilon-mutated, mismatch repair-deficient, p53 abnormal, and non-specific molecular profile tumors. The transition from the chemotherapy era to the age of targeted agents and immunotherapy, which started later in endometrial cancer than in many other tumor types, requires widespread availability of specialized pathology and access to novel agents. Likewise, surgical expertise and state-of-the-art radiotherapy modalities are required to ensure adequate care. Nevertheless, Latin American countries still face considerable barriers to implementation of international guidelines. As we witness the dawn of precision medicine as applied to endometrial cancer, we must make continued efforts towards improving the quality of care in this region. The current article discusses some of these challenges and possible solutions., Competing Interests: Competing interests: AB has received speaker fees from GSK. FMC has received speaker fees from GSK, AstraZeneca, Daiichi Sankyo, Roche, and MSD. AN-R has received speaker fees from Roche, MSD, AstraZeneca, Eisai, Daiichi Sankyo, Novartis, Pfizer, and Eli Lilly, and travel grants from Roche, MSD, AstraZeneca, Eisai, and Daiichi Sankyo. GG has received honoraria for conferences, advisory boards, and travel expenses from AstraZeneca, GSK, Roche, MSD, Raffo, Pink Pharma, and Bayer. MRM has received fees from Allarity Therapeutics, AstraZeneca, BIOCAD, BioNTech, Boehringer Ingelheim, Clovis, Daiichi Sankyo, Eisai, Genmab, GSK, Immunogen, Karyopharm, Merck, Mersana, Novartis, Regeneron, Roche, Seagen, Takeda, and Zaila, and is a member of the board of directors, and hold shares at Karyopharm and Sera Prognostics., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin-containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population-based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age- and sex-matched comparators from the background population. Median follow-up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30-3.68]), with a 10-year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35-26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43-2.76]), with a 10-year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43-1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B-symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work-up of pulmonary symptoms., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Radiotherapy developed empirically through experience balancing tumour control and normal tissue toxicities. Early simple mathematical models formalized this practical knowledge and enabled effective cancer treatment to date. Remarkable advances in technology, computing, and experimental biology now create opportunities to incorporate this knowledge into enhanced computational models. The ESTRO DREAM (Dose Response, Experiment, Analysis, Modelling) workshop brought together experts across disciplines to pursue the vision of personalized radiotherapy for optimal outcomes through advanced modelling. The ultimate vision is leveraging quantitative models dynamically during therapy to ultimately achieve truly adaptive and biologically guided radiotherapy at the population as well as individual patient-based levels. This requires the generation of models that inform response-based adaptations, individually optimized delivery and enable biological monitoring to provide decision support to clinicians. The goal is expanding to models that can drive the realization of personalized therapy for optimal outcomes. This position paper provides their propositions that describe how innovations in biology, physics, mathematics, and data science including AI could inform models and improve predictions. It consolidates the DREAM team's consensus on scientific priorities and organizational requirements. Scientifically, it stresses the need for rigorous, multifaceted model development, comprehensive validation and clinical applicability and significance. Organizationally, it reinforces the prerequisites of interdisciplinary research and collaboration between physicians, medical physicists, radiobiologists, and computational scientists throughout model development. Solely by a shared understanding of clinical needs, biological mechanisms, and computational methods, more informed models can be created. Future research environment and support must facilitate this integrative method of operation across multiple disciplines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Our prospective international survey evaluated the impact of the early phase of the COVID-19 pandemic on the management gynaecological malignancies from the multidisciplinary physicians' perspective with particular focus on clinical infrastructures and trial participation., Methods: Our survey consisted of 53 COVID-related questions. It was sent to healthcare professionals in gynaecological oncology centres across Europe and Pan-Arabian region via the study groups and gynaecological societies from April 2020 to October 2020. All healthcare professionals treating gynaecological cancers were able to participate in our survey., Results: A total of 255 answers were collected from 30 countries. The majority (73%) of participants were gynaecological oncologists from university hospitals (71%) with at least an Intensive Care Unit with cardiopulmonary support available at their institutions. Most institutions continued to perform elective surgeries only for oncological cases (98%). Patients had to wait on average 2 weeks longer for their surgery appointments compared to previous years (range 0-12 weeks). Most cases that were prioritised for surgical intervention across all gynaecological tumours were early-stage disease (74%), primary situation (61%) and good ECOG status (63%). The radicality of surgery did not change in the majority of cases (78%) across all tumour types. During the pandemic, only 38% of clinicians stated they would start a new clinical trial. Almost half of the participants stated the pandemic negatively impacted the financial structure and support for clinical trials. Approximately 20% of clinicians did not feel well-informed regarding clinical algorithm for COVID-19 patients throughout the pandemic. Thirty percent stated that they are currently having trouble in providing adequate medical care due to staff shortage., Conclusion: Despite well-established guidelines, pandemic clearly affected clinical research and patientcare. Our survey underlines the necessity for building robust emergency algorithms tailored to gynaecological oncology to minimise negative impact in crises and to preserve access to clinical trials., (© 2024. The Author(s).)