Munn K, Lawrence R, Haboubi H
… +11 more, Naser H, Hurlow K, Shah UK, Williams L, Gwynne S, Bodger O, Zavadil J, Virard F, Doak S, Thomas LE, Jenkins G
Int J Cancer
· 2026 Apr · PMID 42033079
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We investigated mechanisms underlying circulating DNA damage across the gastro-oesophageal reflux disease (GORD), Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) spectrum using the lymphocyte micronucleus...We investigated mechanisms underlying circulating DNA damage across the gastro-oesophageal reflux disease (GORD), Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) spectrum using the lymphocyte micronucleus (MN) assay. MN frequency (MN%) was quantified in lymphocytes from healthy volunteers (HVs), GORD, BO and OAC patients, alongside plasma biomarkers of inflammation and oxidative stress. Ex vivo challenge assays assessed lymphocyte responses to hydrogen peroxide (HO), vinblastine and the bile acid deoxycholic acid (DCA). Tissue-based NF-κB expression was also correlated with MN levels. OAC patients exhibited significantly elevated MN% compared with HVs (p < 0.001), GORD (p < 0.001) and BO (p = 0.016). OAC lymphocytes showed increased sensitivity to vinblastine relative to HVs (p = 0.025) and GORD patients (p = 0.033). Higher baseline MN% correlated with reduced inducible MN formation following HO or DCA, suggesting altered oxidative stress responses. MN% also associated with plasma 8-OHdG, IL-8 and 2'3'-cGAMP, and with reduced oesophageal tissue IκB, indicating activation of oxidative and cGAS-STING/NF-κB signalling. These findings highlight systemic aneugenic and oxidative stress processes that contribute to lymphocyte MN formation in OAC and suggest that MN% may serve as a minimally invasive indicator of inflammation-linked genomic instability. Further investigation is needed to determine its relevance to OAC progression.
Hüneburg R, van Bokhorst QNE, Dekker E
… +1 more, Nattermann J
Int J Cancer
· 2026 Apr · PMID 42032838
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Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome and is characterized by an accelerated adenoma-carcinoma sequence, a relatively higher prevalence of flat and subtle CRC precursor lesion...Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome and is characterized by an accelerated adenoma-carcinoma sequence, a relatively higher prevalence of flat and subtle CRC precursor lesions, and exceptionally high adenoma miss rates despite intensive colonoscopy surveillance. Artificial intelligence (AI), particularly through computer-aided detection (CADe), has demonstrated substantial improvements in adenoma detection in average-risk CRC screening and surveillance populations. Meanwhile, it is unclear whether these benefits also translate to LS, where carcinogenesis, surveillance regimens, and clinical standards differ fundamentally. This narrative review synthesizes the current evidence on AI-assisted colonoscopy in LS, including findings from the randomized controlled CADLY and TIMELY trials. We contextualize these results within the broader body of research on AI-assisted colonoscopy in average-risk CRC screening and surveillance populations. Existing LS-specific data suggest that AI can be safely integrated into high-quality surveillance. Meanwhile, use of AI has not yet been demonstrated to aid in improving overall adenoma or advanced neoplasia detection rates when used by expert colonoscopists, and when adequate baseline procedural quality is guaranteed.
Salim SK, Shaikh MV, Wei J
… +20 more, Maich WT, Anand A, Tang OY, Subapanditha MK, Alizada Z, Suk Y, Singh M, Zhai K, Khanna A, Brakel B, Dimitrov V, Tabunshchyk Z, Chan K, Brown KR, Vora P, O'Rourke DM, Binder ZA, Venugopal C, Moffat J, Singh SK
Int J Cancer
· 2026 Apr · PMID 42031691
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Glioblastoma (GBM) is the most common malignant brain tumor in adults, with a poor prognosis despite aggressive standard of care. Chimeric antigen receptor T-cell (CAR-T) therapy has shown promising results in liquid mal...Glioblastoma (GBM) is the most common malignant brain tumor in adults, with a poor prognosis despite aggressive standard of care. Chimeric antigen receptor T-cell (CAR-T) therapy has shown promising results in liquid malignancies, but clinical trials in GBM targeting various tumor antigens have not shown durable clinical benefit. While this may be attributable to various tumor-intrinsic immune evasion strategies characteristic of GBM, little work has been done to assess whether the issue is due to the quality of the CAR-T treatment itself. Currently, CAR-Ts for GBMs and liquid malignancies are manufactured in an autologous setting in which T-cells are extracted from patients, engineered ex vivo, and subsequently reinfused back. However, peripheral T-cells taken from untreated GBM patients have demonstrated qualitative and functional deficits, which may contribute to suboptimal treatment outcomes. Thus, we aimed to establish whether CAR-Ts generated from GBM patients would show reduced efficacy in comparison to healthy donors using our previously validated CD133 CAR-T. In this work, we show pre-treatment exhaustion and reduced survival advantage in autologous, patient-derived CD133-targeting CAR-T cell products using an orthotopic xenograft model of human GBM. To overcome the functional and logistical considerations of autologous therapy, we additionally aimed to generate an "off-the-shelf" allogeneic CD133 CAR-T. Using CRISPR gene editing technology, we generated TCR-knockout CAR-T cells with comparable pre-clinical efficacy to our autologous models. Ultimately, this work highlights the need to reassess autologous CAR-T therapy for GBM and consider allogeneic approaches as biologically informed therapeutic alternatives.
Monberg TJ, Lorentzen CL, Westergaard MCW
… +7 more, Iversen TZ, Borch TH, Donia M, Mannering SM, Banke SEW, Met Ö, Svane IM
Int J Cancer
· 2026 Apr · PMID 42026768
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Patients with ovarian cancer (OC) have not yet benefitted from the advances in immuno-oncology. While tumor infiltrating lymphocytes (TILs) can be expanded from OC tumors, previous trials have not demonstrated lasting re...Patients with ovarian cancer (OC) have not yet benefitted from the advances in immuno-oncology. While tumor infiltrating lymphocytes (TILs) can be expanded from OC tumors, previous trials have not demonstrated lasting responses. High expression of the immune checkpoints PD-1 and LAG-3 on TILs from OC provide a rationale for the addition of immune checkpoint inhibitors (ICI) to the treatment. In this clinical pilot study (NCT04611126), five patients with platinum-resistant recurrent OC were treated with TIL therapy and up to four cycles of combined treatment with PD-1-/LAG-3-inhibitors. The primary endpoint was safety and feasibility, while secondary endpoints included immune monitoring and clinical efficacy. Included patients had undifferentiated carcinoma (n = 1), high-grade serous OC (HGSOC) (n = 2) and low-grade serous OC (LGSOC) (n = 2). The treatment was safe and feasible with expected treatment-related toxicity; however, there was a relatively high rate of non-treatment-related complications. A decrease in tumor burden was observed in 80% (4/5) of patients, including two unconfirmed partial responses. In one patient, the response was supported by in vitro reactivity of the infused TILs toward autologous tumor cell line. Differences in baseline tumor burden, infusion product composition and responses were observed in LGSOC vs. HGSOC. Overall, this exploratory pilot study demonstrated a favorable safety profile and indications of clinical efficacy for TIL therapy combined with PD-1 and LAG-3 inhibition in platinum-resistant OC. Due to the low patient number, the results should be interpreted as hypothesis-generating, providing a rationale for conducting larger trials that carefully consider treatment timing and tumor histology.
Chiu HC, Chiang CJ, Jhuang JR
… +4 more, Tsai DR, Lin LJ, Wang JF, Lee WC
Int J Cancer
· 2026 Apr · PMID 42026743
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Cancer remains a major global health burden. Taiwan launched the Cancer Care Quality Certification (CCQC) program in 2008; however, comprehensive evaluations of its association with survival across multiple cancer types...Cancer remains a major global health burden. Taiwan launched the Cancer Care Quality Certification (CCQC) program in 2008; however, comprehensive evaluations of its association with survival across multiple cancer types remain limited. A total of 294,323 patients diagnosed with one of eight cancer types between 2011 and 2017 were identified from the Taiwan Cancer Registry Database. Overall survival among patients treated at certified versus non-certified hospitals was compared using Cox proportional hazards models incorporating a hospital-level shared frailty to account for institutional heterogeneity, adjusting for age, sex, stage, hospital level, geographic region, and treatment modalities. Treatment at certified hospitals was associated with lower all-cause mortality for colorectal (adjusted hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.83-0.93), lung (HR, 0.91; 95% CI, 0.87-0.96), and bladder cancers (HR, 0.79; 95% CI, 0.66-0.96). No statistically significant associations were observed for liver, female breast, cervical, uterine, or ovarian cancers. In this population-based study, the CCQC program in Taiwan is associated with improved survival for several major cancers, although the magnitude of association varied by cancer type. These findings suggest that certification may serve as a marker of institutional capacity for delivering high-quality cancer care and support the continued evaluation of certification programs as a potential strategy for strengthening cancer care systems.
Han Z, Yi X, Tang Y
… +5 more, Li X, Liao D, Xu H, Zheng X, Ai J
Int J Cancer
· 2026 Apr · PMID 42017392
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Although immunotherapy has transformed the treatment of several genitourinary malignancies, its role in prostate cancer remains limited. Combining immunotherapy with targeted therapies has emerged as a promising approach...Although immunotherapy has transformed the treatment of several genitourinary malignancies, its role in prostate cancer remains limited. Combining immunotherapy with targeted therapies has emerged as a promising approach to enhance immune responses in prostate cancer. We aimed to systematically evaluate the efficacy and safety of immunotherapy combined with targeted therapy in the treatment of prostate cancer. We conducted a detailed literature search across Embase, Scopus, PubMed, Web of Science, and the Cochrane Library to include clinical trials enrolling adults with histologically confirmed prostate cancer treated with a combination of targeted therapy and immunotherapy. A systematic review and meta-analysis were performed according to a registered protocol. A total of 21 studies from 19 clinical trials, encompassing 5702 participants, were included. The studies evaluated 12 unique therapeutic combinations involving six targeted agents and four immunotherapies. Seven trials compared combination therapy with monotherapy. Pooled analyses showed that combination therapy significantly improved disease control rate (RR = 1.42), complete response (RR = 2.56), and partial response (RR = 2.13), albeit with a higher incidence of adverse events. In single-arm studies, the pooled median progression-free survival was 5.14 months, and median overall survival was 16.79 months. The androgen receptor signaling inhibitor subgroup exhibited longer survival than the PARP inhibitor subgroup. Combination immunotherapy and targeted therapy demonstrate superior efficacy over monotherapy in prostate cancer but increase the risk of toxicity. These promising results warrant further validation in large-scale, well-designed randomized trials.
Brentnall AR, Rebolj M, Sasieni P
… +3 more, Funston G, Gabe R, Vickers AJ
Int J Cancer
· 2026 Apr · PMID 42015666
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Prostate cancer overdiagnosis is detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. It is a major concern to policymakers due to its impact on qua...Prostate cancer overdiagnosis is detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. It is a major concern to policymakers due to its impact on quality of life. We used long-term follow-up data from the CAP randomised trial of a one-off screen, and English male competing mortality rates (2021-23), to estimate the impact of age on excess prostate cancer incidence within 15 years ('overdiagnosis') using competing-risks methods. In total, 2249 (1.19%) of 189,386 men invited for a PSA test in CAP had cancer detected at the one-off screen. Prostate cancer cumulative incidence at 15 years was 7.08% (95% CI 6.95%-7.21%) in those invited to screening, compared with 6.94% (95% CI 6.82%-7.06%) in the control arm; an absolute excess incidence difference of 0.14% (95% CI -0.04% to 0.37%). Excess net incidence to 15 years was 0.14/1.19 = 11.7% (95% CI 0.0%-26.7%) of cases detected at a single prevalent screen. Accounting for competing mortality, men diagnosed at screening aged 50 years were projected to have a 16% chance the cancer would not have been detected within 15 years, rising to 32% if detected at screening aged 70 years and 58% aged 80 years. Thus, prostate cancer overdiagnosis rises substantially with age due to competing mortality, and is relatively low for younger men. Accordingly, policies that enable opportunistic testing should be re-examined in settings where they have led to high rates of screening in older men.
Liu J, Tang M, Xuan J
… +10 more, Tang T, Zhong Y, Ma J, Liu L, Yang Z, Wei W, Wang H, Wang K, Shen F, Xia Y
Int J Cancer
· 2026 Apr · PMID 42015536
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To compare targeted immunotherapy plus adjuvant transarterial chemoembolization (TACE) versus TACE alone in patients with borderline resectable hepatocellular carcinoma (BR-HCC). 297 BR-HCC patients who underwent liver r...To compare targeted immunotherapy plus adjuvant transarterial chemoembolization (TACE) versus TACE alone in patients with borderline resectable hepatocellular carcinoma (BR-HCC). 297 BR-HCC patients who underwent liver resection were included. Among them, 86 patients received perioperative targeted immunotherapy combined with adjuvant TACE (combination therapy group, which included neoadjuvant therapy and adjuvant therapy), while 211 received adjuvant TACE alone (TACE-only group). After propensity score matching (PSM), the combination therapy group demonstrated significantly improved 1-, 3-, and 5-year OS rates (90.7%, 66.0%, and 58.1%, respectively) compared to the TACE-only group (86.0%, 55.2%, and 35.1%; p = 0.013). Similarly, 1-, 3-, and 5-year RFS rates were higher in the combination therapy group (66.3%, 36.9%, and 31.0%) than in the TACE-only group (55.8%, 23.1%, and 13.8%; p = 0.007). Multivariable analysis confirmed that combination therapy was an independent protective factor for both OS (HR: 0.619, 95% CI: 0.389-0.983) and RFS (0.665, 0.469-0.944). Subgroup analysis showed that in adjuvant therapy and TACE-only, TACE-only was an independent risk factor for OS (1.986, 1.105-3.566) and RFS (1.831, 1.132-2.962) compared with adjuvant therapy (receiving postoperative adjuvant targeted immunotherapy and TACE). Further analysis showed that in the combination therapy subgroup, adjuvant therapy was an independent risk factor for OS (2.701, 1.171-6.230) and RFS (2.051, 1.125-3.739) compared to neoadjuvant therapy (receiving both preoperative neoadjuvant and postoperative adjuvant targeted immunotherapy and TACE). No significant difference in complications/AEs following surgery/TACE was observed between the two groups. Perioperative targeted immunotherapy combined with adjuvant TACE significantly improves OS and RFS in BR-HCC patients without increasing the incidence of complications/AEs following surgery/TACE.
Stoff R, Bilgin GB, Nikanpour Y
… +6 more, Johnson GB, Kipp BR, Zahrieh DM, Geiersbach KB, Block MS, Markovic SN
Int J Cancer
· 2026 Aug · PMID 42011804
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Circulating tumor DNA (ctDNA) as a liquid biopsy is an emerging tool used for diagnosis and disease monitoring, yet not all tumors shed DNA equally, thus currently limiting the clinical applicability of this tool. Our in...Circulating tumor DNA (ctDNA) as a liquid biopsy is an emerging tool used for diagnosis and disease monitoring, yet not all tumors shed DNA equally, thus currently limiting the clinical applicability of this tool. Our institution has developed and validated a droplet digital Polymerase Chain Reaction (ddPCR) ctDNA test for BRAF V600 mutation. We collected data on all BRAF mutated melanoma patients tested with the ddPCR BRAF assay at our institution over the years 2018-2024 and correlated the test results with clinical and radiological baseline parameters, with a focus on Positron Emission Tomography-Computed Tomography (PET-CT) data, incorporating both location of lesions and volume of disease. Linear and logistic regression modelling was used to assess possible associations between the baseline parameters and the ctDNA results. We identified 71 BRAF mutated melanoma patients, of which 65 had active disease on imaging studies and 43 had PET-CT data available for analysis. Multivariate modelling has shown that patients were more likely to have a positive ctDNA result if they had elevated serum lactate dehydrogenase (LDH) (OR = 9.9), had a higher number of lesions on imaging studies (> 10 lesions: OR = 11.3), and if they were younger than 65 (OR = 11.8), with an AUC of 0.84. The PET-CT calculated total metabolic tumor volume correlated with the quantitative ctDNA result with a Pearson r factor of 0.49. In conclusion, ctDNA ddPCR BRAF testing is easily obtained and might be especially beneficial for patients diagnosed with a clinically aggressive disease, based on elevated LDH, higher PET-CT metabolic tumor volume, and younger age.
de Abreu M, Kowalski LP, López RM
… +39 more, Barul C, Radoi L, Bidoli E, Polesel J, Wunsch-Filho V, Olshan AF, Zevallos J, Negri E, Edefonti V, Świątkowska B, Mates D, Fabianova E, Lissowska J, Shangina O, Brennan P, Pandics T, Maso LD, Morgenstern H, Zhang ZF, Kelsey K, McClean M, La Vecchia C, Garavello W, Chen C, Schwartz SM, Ramroth H, Winkler V, Cadoni G, Boccia S, Brenner H, D'Souza G, Gross N, Muscat J, Abedini M, Sassano M, Boffetta P, Hashibe M, Lee YA, Curado MP
Int J Cancer
· 2026 Apr · PMID 42011792
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This study investigated risk factors associated with HNC by subsite including oral cavity cancer (OCC), oropharyngeal cancer (OPC), and laryngeal cancer (LC) among former smokers in the International Head and Neck Cancer...This study investigated risk factors associated with HNC by subsite including oral cavity cancer (OCC), oropharyngeal cancer (OPC), and laryngeal cancer (LC) among former smokers in the International Head and Neck Cancer Epidemiology Consortium (INHANCE). Case-control study including former smokers from the pooled INHANCE data, with information on sociodemographic, smoking, and alcohol history. Associations were assessed using logistic regression with 95% confidence intervals (CI). The study included 2143 cases with HNC and 5799 controls. Cancer cases were categorized by their respective subsites: 954 LC (44.5%), 685 OPC (32.0%), 504 OCC (23.5%). The risk of developing OCC was 2.8-fold higher [CI: 1.9-4.1], LC 2.6-fold higher [CI: 1.9-3.5], and OPC 2.1-fold higher [CI: 1.5-2.8] in individuals who smoked > 50 pack-years, compared to < 10 pack-years. The risk of OCC/OPC/LC increased with tobacco consumption in North-America, whereas in Western/Southern-Europe and South-America the association plateaued beyond 31-50 pack-years. Cessation after age 55 increased the risk of LC by 3.0-fold [CI: 2.2-4.2], and OCC by 2.2-fold [CI: 1.4-3.3] versus cessation age ≤ 45 years. Consuming ≥ 5 drinks/day was associated with 5-fold higher risk of OPC [CI: 3.7-6.6], 4.4-fold higher risk of OCC [CI: 3.2-6.1] and 3.1-fold higher risk of LC [CI: 2.4-3.9] compared to 0-0.9 drinks/day. The risk of HNC among former smokers is not homogeneous across regions and that there were distinct patterns for OCC, OPC, and LC. The amount of tobacco and alcohol consumption are key risk factors, with alcohol being more important for OCC/OPC, and tobacco being more strongly associated with LC risk.
Marinho MFP, da Fonseca Simas KB, Heras PV
… +6 more, da Cruz CAS, Dos Santos Bessa AM, Romãnach MJ, Abrahão AC, Visconti MA, Agostini M
Int J Cancer
· 2026 Apr · PMID 42011789
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This randomized clinical trial assessed the performance of organized, risk-based oral cancer (OC) screening strategies compared with the conventional opportunistic approach. Conducted from December 2023 to December 2024...This randomized clinical trial assessed the performance of organized, risk-based oral cancer (OC) screening strategies compared with the conventional opportunistic approach. Conducted from December 2023 to December 2024 across 35 primary health care (PHC) units in Rio de Janeiro, Brazil, the study included adults aged ≥ 35 years identified as tobacco users in the public electronic medical record system and considered high-risk for preventive oral examination (POE). PHC units were allocated to three groups: control (opportunistic screening without active invitation; 12 units), experimental I (organized invitation for POE plus home-visit support; 11 units), and experimental II (organized invitation for POE plus an awareness campaign; 12 units). The 23 PHC units implementing organized screening included 2735 registered tobacco users, whereas the 12 units maintaining opportunistic screening included 1048. Consequently, POE coverage reached 77.2% in the organized screening arms versus 3.6% under opportunistic screening (p < 0.05). POE adherence was higher with organized invitation plus community awareness (77.2%) than with home-visit support (58.1%). A total of 15 biopsies were performed within the organized screening groups, identifying 6 cases of oral potentially malignant disorders and 5 cases of OC. In contrast, biopsies conducted outside the screening program demonstrated significantly lower detection rates (p < 0.0001). These findings demonstrate that organized, invitation-based screening integrated into PHC can substantially expand access to early diagnosis among high-risk and socially vulnerable individuals who would otherwise remain unscreened, reinforcing PHC as a strategic and equitable setting for sustainable early OC detection.
Matos A, Cawthorn WP, Marinho-Dias J
… +20 more, Ramalheira S, Roncon S, Pereira D, Ribeiro T, Rodrigues C, Mariz M, Miranda A, Brízido H, Bicho M, Medeiros P, Carneiro A, Trigo F, Hu P, Pereira F, Duarte H, Gray CD, Macgillivray T, Ramsay AG, Oliveira MJ, Ribeiro R
Int J Cancer
· 2026 Aug · PMID 42003764
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Excess adiposity has been associated with Hodgkin lymphoma (HL) development, but its implications remain unclear. Bone marrow (BM), a frequent extranodal involvement site, contains both red and fatty yellow marrow. We in...Excess adiposity has been associated with Hodgkin lymphoma (HL) development, but its implications remain unclear. Bone marrow (BM), a frequent extranodal involvement site, contains both red and fatty yellow marrow. We investigated whether obesity influences HL outcomes and characterized the BM and cytokine profiles. In this retrospective study, HL patients were analyzed to assess the association between obesity with relapse and mortality. Yellow and red marrow composition were evaluated using CT imaging and correlated with HL outcomes. A nested study analyzed cytokines in the interstitial marrow fluid (IMF) and in circulation of HL patients, in comparison to a control group of healthy blood donors. Further, in vitro functional analyses were performed. Overweight/obesity in HL patients was associated with lower rates of BM involvement, disease relapse, and mortality. Moreover, dense yellow marrow was related to increased risk of death. HL subjects had elevated levels of adiponectin in IMF compared to marrow donors, whereas higher insulin, interleukin 8, and osteoprotegerin levels in IMF were associated with shorter time to relapse. At the molecular level in BM, HL patients had overexpression of LEPR and IGFBP3 in adipocytes, while stromal cells overexpressed IGF-axis receptors. In in vitro studies, human recombinant IGF-1 significantly induced the L428 HL cell line proliferation, which when combined with IGFBP-3 modified apoptosis. The current findings suggest that obesity is associated with a lower incidence of BM involvement and mortality in patients with HL. The obesity together with HL mechanistically influences systemic and local BM cytokine production, thereby impacting HL fate.
Niedermaier B, Bochtler T, Eichhorn F
… +17 more, Griffo R, Klotz LV, Allgäuer M, Stenzinger A, Bischoff H, Schneider MA, Christopoulos P, Haberkorn U, Heussel CP, Zoernig I, Herth FJF, Thomas M, Rölle A, Winter H, Benner A, Jaeger D, Eichhorn ME
Int J Cancer
· 2026 Apr · PMID 42003237
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Immune checkpoint inhibitors have shown promising results in the neoadjuvant treatment of resectable non-small cell lung cancer. This open-label, single-arm, prospective, monocentric trial evaluated the efficacy and safe...Immune checkpoint inhibitors have shown promising results in the neoadjuvant treatment of resectable non-small cell lung cancer. This open-label, single-arm, prospective, monocentric trial evaluated the efficacy and safety of neoadjuvant atezolizumab plus carboplatin/nab-paclitaxel in patients with resectable non-squamous non-small cell lung cancer. Patients with previously untreated, pathologically confirmed, non-squamous non-small cell lung cancer in stage II, IIIA, and select IIIB (T3N2 only) were treated with atezolizumab and carboplatin/nab-paclitaxel for 3 cycles followed by curative intent surgery. Major pathologic response (MPR) was defined as primary endpoint. 20 patients with histologically confirmed pulmonary adenocarcinoma in TNM-stage IIA (n = 1, 5%), stage IIB (n = 7, 35%), and stage IIIA (n = 12, 60%) were enrolled and treated according to the study protocol. 151 treatment-related adverse events were recorded, and 13 patients (65%) had treatment-related adverse events of grade 3 or higher. There were no grade 5 events. All patients underwent complete anatomical resection (R0). MPR was observed in 9 patients (45%), including 5 (25%) patients with complete pathological response. The proportion of remaining viable tumor showed a significant but weak association to the relative tumor size change in CT (p = 0.018) and the relative change in SUV (p = 0.006). In conclusion, neoadjuvant chemoimmunotherapy with atezolizumab achieved a promising MPR-rate of 45% while being well tolerated and allowing a safe and complete surgical resection. These results strongly support the further investigation of atezolizumab as preoperative therapy in resectable non-small cell lung cancer and underline the continued need to develop biomarkers of response.
Kühnel B, Schneiderbauer S, Lange S
… +16 more, Wilhelm D, Friess H, Feith M, Ehmer U, Bassermann F, Holch JW, Munker SM, Neumann J, Werner J, Stein HJ, Fey T, Mansmann U, Algül H, Berger-Thürmel K, Maurer HC, Nasseh D
Int J Cancer
· 2026 Aug · PMID 41999201
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Accurate cancer staging is essential for cancer research and treatment evaluation; however, real-world data (RWD) often include incomplete or inconsistent UICC classifications. We present the development, optimization, d...Accurate cancer staging is essential for cancer research and treatment evaluation; however, real-world data (RWD) often include incomplete or inconsistent UICC classifications. We present the development, optimization, demonstration, and release of the Munich UICC Staging Tool (MUST), an open-source R script that automates UICC staging based on TNM classifications and tumor characteristics, improving data completeness and consistency. MUST incorporates official UICC staging rules (6th-8th editions). A key feature is the application of RWD-specific rules to handle missing values and incomplete information. The tool is transparent, highly customizable, and adaptable to future TNM versions and diverse applications. MUST was validated using anonymized clinical tumor registry data from two Munich university hospitals (analyzed independently, n > 100,000), focusing on pancreatic and stomach cancers. Compared to documented UICC stages, MUST increased staging completeness from 60% to 72% in Clinic-1 and from 20% to 74% in Clinc-2. Agreement rates between documented and MUST-generated UICC stages were 90% in Clinic-1 and 95% in Clinic-2. To assess reliability, a Confidence Level metric summarizes the proportion of original versus additional rules applied. 70% of MUST-derived stages in Clinic-1 and 48% in Clinic-2 were classified as "Assured," with the remaining cases relying on RWD-specific rules. The results demonstrate that RWD-specific rules substantially improve completeness, while the differences between clinics highlight variations in documentation and coding practices. MUST offers a reliable solution for UICC staging, addressing documentation gaps and improving data quality. Its adaptability makes it valuable for clinical documentation, registries, and large-scale oncology studies.
Pantelaiou-Prokaki G, Bamahmoud H, Georges NS
… +10 more, Jansari S, Jung A, Grimm D, Prokakis E, Gayer FA, Deldar M, Dullin C, Gallwas J, Wegwitz F, Alves F
Int J Cancer
· 2026 Apr · PMID 41999194
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Basal-like breast cancer (BLBC) is characterized as the most aggressive and poorly understood breast cancer (BC) subtype. Next to surgery, conventional chemotherapy and immunotherapy, radiotherapy (RT) represents one of...Basal-like breast cancer (BLBC) is characterized as the most aggressive and poorly understood breast cancer (BC) subtype. Next to surgery, conventional chemotherapy and immunotherapy, radiotherapy (RT) represents one of the primary treatment options. Transcriptional plasticity is largely responsible for BLBC's ability to rapidly adapt to genotoxic stress, enabling cell survival, tumor repopulation, and disease progression. Our research group has recently shown that chemotherapy primarily elicits the epithelial-to-mesenchymal transition (EMT) transcriptomic program by epigenetically derepressing the expression of several important EMT-promoting factors, which are crucial for drug tolerance and disease relapse. However, the induced transcriptomic programs upon RT in BLBC have been elusively addressed. To fill this gap, we leveraged high-throughput bulk and spatial transcriptomic data in a syngeneic mouse model of BLBC, corroborated by publicly available patient-derived bulk transcriptomic data and combined with an in vitro 3D BLBC model approach. Contrary to our expectations, we found that irradiated basal-like breast cancer (BLBC) tumors shifted their epithelial/mesenchymal hybrid state toward a stronger epithelial gene expression program, ultimately driving MUC1 (Mucin 1) expression as a key mediator of cell survival following RT. Altogether, our study uncovers a new aspect of the BLBC transcriptional plasticity elicited by RT, leading to a distinct hybrid phenotypic state from that upon chemotherapy. Concluding, these data underscore the potential clinical value of MUC1 as a therapeutic target or prognostic marker to optimize BLBC patients' response to RT.
Wang H, Li J, Cao L
… +8 more, Zhang Y, Wan X, Wang X, Zhao Y, Li Z, Chen C, Song Y, Bai O
Int J Cancer
· 2026 Apr · PMID 41999193
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To evaluate the efficacy and safety of the RMT regimen as first-line induction therapy for primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL), we retrospectively analyzed 36 patients treated with 4...To evaluate the efficacy and safety of the RMT regimen as first-line induction therapy for primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL), we retrospectively analyzed 36 patients treated with 4-6 cycles of RMT. After 4 induction cycles, the overall response rate and complete response rate were 97.2% and 80.6%, respectively. With a median follow-up of 19.9 months, the 2-year progression-free survival (PFS) and overall survival rates were 64.4% and 79.3%. The 2-year PFS was 100% in patients receiving sequential autologous stem cell transplantation (ASCT), 67.9% with maintenance therapy (BTKi/IMiD), and 45.5% with induction only. The most common Grades 3-4 adverse event was neutropenia (33.3%); all were manageable without treatment discontinuation. These findings indicate that the RMT regimen demonstrates excellent efficacy and a favorable safety profile in PCNS-DLBCL, including elderly patients; sequential ASCT is the preferred consolidation strategy, while BTKi/IMiD maintenance provides a viable alternative for sustained disease control.
Int J Cancer
· 2026 Aug · PMID 41998812
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While thyroid cancer generally carries a favorable prognosis, the 5-year survival rate for advanced cases, particularly poorly differentiated and anaplastic subtypes, remains below 20%. The latest guidelines recommend co...While thyroid cancer generally carries a favorable prognosis, the 5-year survival rate for advanced cases, particularly poorly differentiated and anaplastic subtypes, remains below 20%. The latest guidelines recommend conservative use of chemotherapy in thyroid cancer, primarily due to the absence of reliable efficacy prediction systems. Tumor-derived organoid-based strategies represent a powerful tool for assessing individual-level drug sensitivity and identifying novel treatment regimens. This prospective single-arm cohort study enrolled 25 patients. Thyroid tumor tissue was procured via ultrasound-guided core needle biopsy, and organoids were established using a modified Matrigel-air-liquid interface culture method. Drug sensitivity testing encompassed clinically relevant chemotherapeutic agents, utilizing IC50 values as the primary parameter for formulating individualized regimens. Eventually, the objective response rate (ORR) of 15 patients who received the recommended regimens reached 53.3%, among which the ORR of patients with anaplastic thyroid carcinoma (ATC) was as high as 87.5%. The tumor diameters of the patients were significantly reduced, with a median reduction of 40.32% (IQR: 7.89%-65.22%), and 80% of the patients had a progression-free survival (PFS) exceeding 6 months. This preliminary study confirmed the feasibility of extracting and culturing tumor organoids from patients' tumor lesions, which can serve as an effective tool for chemotherapy drug screening, highlighting the potential of precision medicine in individualized chemotherapy for locally advanced thyroid carcinoma (LATC).